Epilepsia Epicongress

Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.
ABSTRACT
10th European Congress on Epileptology London, UK, 30 September4 October 2012
Genetics 1 Monday, 01 October 2012

001 IDENTIFICATION OF NOVEL SYNTAXIN BINDING PROTEIN 1 (STXBP1) MUTATIONS IN PATIENTS WITH SEVERE EARLY ONSET EPILEPTIC ENCEPHALOPATHIES (EOEE) T. Djmi*, P. Holmgren, S. Weckhuysen, A. Suls, A. Jansen, D. Hasaerts, C. Dielman, L. L. Klitten, S. Von Spiczak**, I. Helbig**, R. S. Mller, I. E. Scheffer, H. Hjalgrim, and P. De Jonghe *University of Antwerp, Antwerp, Belgium; VIB, Antwerp, Belgium; Epilepsy Centre Kempenhaeghe, Oosterhout, The Netherlands; UZ Brussel, Brussel, Belgium; University of Copenhagen, Copenhagen, Denmark; **University Medical Center Schleswig-Holstein, Kiel, Germany; Danish Epilepsy Centre, Dianalund, Denmark; University of Melbourne, Melbourne, Australia; and Institute of Regional Health Services Research, University of Southern Denmark, Odense, Denmark
Purpose: Identification of additional STXBP1 mutations in a large cohort of patients with EOEE and further delineating the phenotype of STXBP1 encephalopathy. Method: We collected a cohort of 171 isolated patients with Ohtahara syndrome, West syndrome and a wide range of unclassified EOEE. Point mutations and deletions in STXBP1 have been described so we used two complementary strategies to detect both classes of variation. First, identification of point mutations was done using Sangersequencing. Subsequently we performed multiplex amplicon quantification (MAQ) analysis for detection of deletions. Result: Four novel STXBP1 point mutations were identified in four patients. Three are missense mutations: p.G544V, p.I77N and p.R551C. The fourth, p.Q203X, is a nonsense mutation. DNA of parents of three patients was available and these mutations were proven to occur de novo. p.G544V was found in a patient with a neonatal epileptic encephalopathy that evolved to West syndrome; p.I77N and Q203X in patients with neonatal epileptic encephalopathy. The patient with the p.I77N mutation later developed epileptic spasms without hypsarrythmia while the patient with the p.R551C mutation had West syndrome from onset. Although one patient became seizure free after 2.5 months, all patients had severe intellectual disability. The MAQ analysis did not reveal any deletions in STXBP1. Conclusion: Our results confirm that patients with an STXBP1 encephalopathy present with severe epilepsy of very early onset and frequently develop spasms early in disease course. Although mutation yield in this study was lower than initially reported, STXBP1 screening should be considered in patients with severe EOEE of unknown etiology.
002 SCREENING FOR SYNGAP1 MUTATIONS IN PATIENTS WITH NON-SYNDROMIC ID AND EPILEPSY WITH MYOCLONIC ABSENCES OR MYOCLONIC ASTATIC EPILEPSY R. S. Mller*, F. F. Hamdan, L. L. Klitten, S. Dobrzeniecka, D. Rochefort, H. Hjalgrim, G. A. Rouleau**, J. L. Michaud, and N. Tommerup *Danish Epilepsy Centre, Dianalund, Denmark; Center of Excellence in Neuroscience of Universit de Montral, Centre de Recherche du CHU Sainte-Justine, Montral, QC, Canada; Wilhelm Johannsen Centre for Functional genome Research, University of Copenhagen, Copenhagen, Denmark; Center of Excellence in Neuroscience of Universit de Montral, Centre de Recherche du Centre Hospitalier de lUniversit de Montral, Department of Medicine, Universit de Montral, Montral, QC, Canada; Institute of Regional Health Services Research, University of Southern Denmark, Odense, Denmark; and **Center of Excellence in Neuroscience of Universit de Montral, Centre de Recherche du Centre Hospitalier de lUniversit de Montral, Universit de Montral, Montral, QC, Canada
Purpose: Epilepsy with Myoclonic Absences (EMA) and Myoclonic Astatic Epilepsy (MAE) are rare and severe childhood-onset epilepsies. The underlying etiologies of these syndromes are largely unsolved, but increasing scientific evidence points to genetic factors for these severe epilepsies. Recently, it was shown that de novo mutations in the brainexpressed synapse gene SYNGAP1 cause Non-Syndromic Intellectual Disability (NSID). Worldwide, a total of 10 patients with mutations in this gene have been described. Surprisingly, 7/10 published patients have early-onset of epilepsy with generalized seizures, mainly manifesting as absence-, myoclonic- and/or atonic seizures. Method: In search for an underlying cause of EMA and MAE, we sequenced the SYNGAP1 gene in a cohort of 25 patients with a combination of NSID and early-onset of generalized seizures. Patients had EMA, MAE or unclassified epilepsy. DNA was extracted from blood and saliva specimens according to standard protocols. Result: In a single female patient we detected a mutation in the SYNGAP1 gene (c.283dupC) which was absent in 669 healthy controls. This mutation was predicted to cause a shift in reading frame and thereby create a truncated protein (p.His95ProX5). Surprisingly, this mutation was inherited from a mildly affected father without epilepsy. A mosaic state of the mutation in the father was detected via cloning and subsequent sequencing of blood- and saliva DNA. Conclusion: We report the second patient with EMA and SYNGAP1 mutation adding more evidence to SYNGAP1-dysfunction as cause of EMA. In this study, we detected the first patient with an inherited SYNGAP1 mutation and mosaicism in a mildly affected parent.
2 Abstracts
003 MUTATIONS IN CDKL5 AS A CAUSE OF EARLY ONSET EPILEPSY ska, M. Gos, D. Hoffman-Zacharska, M. Bartnik, K. Derwin I. Terczynska, H. Mazurkiewicz, T. Mazurczak, P. Stankiewicz, E. Szczepanik, E. Bocian, and J. Bal Institute of Mother and Child, Warsaw, Poland
Purpose: The cyclin-dependent kinase like 5 (CDKL5) gene, encodes serine-threonine kinase involved in the regulation MECP2 and DNA methyltransferase I activities. The aim of the study was the molecular analysis of CDKL5 gene, in which mutations are responsible for severe early onset epileptic encephalopathy with infantile spasms, intellectual impairment and Rett-like phenotype. Method: Together, 29 patients with clinical symptoms suggesting CDKL5 mutation were referred to our laboratory for molecular testing. The multiplex ligation dependent probe amplification (MLPA) method and SALSA MLPA P189 CDKL5 Kit containing probes specific for all CDKL5 exons were applied for the detection of gene deletions. In case of deletion presence, the results were validated with microarray-CGH, quantitative Real-Time PCR, long-range PCR or direct sequencing method. Result: The MLPA analysis revealed the presence of deletions in three children with early onset epilepsy. In two, the deletion encompassed one exon with flanking intron sequences (g.18542246_18553009del10764 deletion of exon 18 and g.18492177-?_18492235+?del deletion of exon 4), in the second case the deletion was present in mosaic state. In the third case, the sequencing analysis revealed the presence of small deletion in exon 6 - c.301_317del17bp (g.18507907_18507923del17) that partially overlapped with the MLPA probe binding site leading to the decrease in MLPA signal. The mutation causes a frame shift starting at codon 101 and creation of premature STOP codon three positions downstream. Further analysis of CDKL5 coding sequence in patients without deletion is in progress. Conclusion: The MLPA analysis allowed to identify molecular cause of early onset epilepsy in 3/29 (10.3%) patients. Purpose: The PRRT2 gene, located on chromosome 16p11.2, is coding for a presynaptic protein interacting with SNAP-25, which is important for the synaptic vesicle forming and transport in the brain. Mutations in PRRT2 have been described in paroxysmal kinesigenic dyskinesia (PKD) and ICCA (PKD with infantile seizures), and recently also in some families with the syndrome of benign familial infantile seizures (BFIS) alone. All syndromes are linked to chromosome 16p12-q12. BFIS is characterized by (complex-)partial and generalized tonic-clonic seizures occurring often in clusters between 3 and 12 months of age typically resolving after weeks to months and normal psychomotor development in the patients. Method: PRRT2 was sequenced in 49 BFIS families and three sporadic cases of Italian, German, Turkish and Japanese origin. Result: We identified the previously described mutation c.649-650insC in an instable series of nine cytosines to occur in 77% of index cases. Furthermore, three novel mutations were found in three other families. Conclusion: Our study reveals PRRT2 as the major gene for BFIS alone. In the presentation, we will describe our cohort and an overview of the mutations found in the different disease entities.
Basic Science 1 Monday, 01 October 2012

005 SEIZURE-INDUCED BRAIN-BORN INFLAMMATION AND BLOOD-BRAIN BARRIER DAMAGE ARE COUNTERACTED BY ANAKINRA IN THE ISOLATED GUINEA PIG BRAIN PREPARATION L. Librizzi*, T. Ravizza, F. No, A. Vezzani, and M. De Curtis* *Neurological Institute C Besta Foundation, Milano, Italy; and Mario Negri Institute for Pharmacological Research, Milano, Italy
Purpose: Recent findings support the concept that brain inflammation is an etiopathogenetic mechanism of epilepsy, promoting seizure precipitation and recurrence. In this study we investigated if seizures induce brain inflammation independently on extracerebral factors and if brain-born inflammation is required and sufficient to maintain seizure activity and support blood-brain barrier (BBB) impairment. For this purpose, we studied the relationship between seizures, inflammation and BBB permeability in a brain preparation isolated from extracerebral compartments. Method: Epileptiform activity was induced by arterial perfusion of bicuculline (50lM), a GABAa receptor antagonist. Seizure-induced brain inflammation was evaluated by quantitative immunohistochemical analysis of IL-1b in parenchymal cells. BBB damage was assessed by extravasation of intravascular FITC-albumin. The effects of arterially-perfused anakinra, a human recombinant IL-1b receptor antagonist, were investigated on epileptiform discharges, brain inflammation and BBB damage. Result: Seizures induction in the absence of extra-cerebral factors promoted the release of IL-1b from brain resident cells and enhanced its biosynthesis in astrocytes. Anakinra rapidly terminated seizures, prevented their recurrence and resolved seizure-associated BBB breackdown. Conclusion: We demonstrated that (i) seizure activity determines a rapid release of IL-1b from intrinsic brain cells, (ii) persistent brain inflammation originates in glia, independently on peripheral factors, (iii)
004 PRRT2 MUTATIONS ARE THE MAJOR CAUSE OF BENIGN FAMILIAL INFANTILE SEIZURES (BFIS) Y. Weber*, J. Schubert*, R. Paravidino, F. Becker*, A. Berger, N. Bebek, A. Bianchi, K. Brockmann**, G. Capovilla, B. Dalla Bernardina, Y. Fukuyama, G. Hoffmann, K. Jurkat-Rott***, A. Antonnen, G. Kurlemann, A. E. Lehesjoki, F. Lehmann-Horn***, M. Mastrangelo, U. Mause****, S. Mller*, B. Neubauer, B. Pst, D. Rating, A. Robbiano, S. Ruf, C. Schroeder, A. Seidel, N. Specchio*****, U. Stephani, P. Striano, J. Teichler, D. Turkdogan, F. Vigevano, M. Viri, P. Bauer, F. Zara, and H. Lerche* *University of Tbingen, Tbingen, Germany; Department of Neuroscience, Genova, Italy; Children's Hospital Harlaching, Munich, Germany; Istanbul, Turkey; Verona, Italy; **Gttingen, Germany; Mantova, Italy; Arezzo, Italy; Tokyo, Japan; Heidelberg, Germany; ***Ulm, Germany; Helsinki, Finland; Mnster, Germany; Finland; Milano, Italy; ****Frankfurt, Germany; Giessen, Germany; Hamburg, Germany; Tbingen, Germany; Celle, Germany; *****Rome, Italy; Kiel, Germany; Gaslini Institute, University of Genova, Genova, Italy; Zrich, Switzerland; and Institute Giannina Gaslini - Lab. Neurogenetics, Genova, Italy
Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x
3 Abstracts
the clinically used the immunomodulator anakinra, abates both seizure duration and their recurrence, and the associated BBB breakdown, supporting the conclusion that brain-borne inflammation, independent on systemic influences, initiates and sustains ictogenesis. This study supports the use of specific anti-inflammatory drugs in clinical conditions that present with recurrent seizures, such as status epilepticus or drugresistant chronic epilepsies. Purpose: Inflammation plays a prominent role in the affected brain tissue in temporal lobe epilepsy, and activation of the complement system is an important component of this response. Better understanding of inflammatory changes and correlation with electrophysiological and imaging characteristics may yield insights into the mechanisms underlying the development of epilepsy. Method: Epilepsy was induced by systemic injection of pilocarpine in Swiss mice. Animals were allocated to 3 groups comprising controls (CON, n=6), those with status epilepticus (SE, n=12) following injection of pilocarpine, and those that did not develop status epilepticus after injection (NoSE, n=6). MR images were acquired at 7 and 35 days after injection. The MR T2 relaxation times and apparent diffusion coefficient (ADC) maps were compared between the groups using voxel-based statistical parametric mapping. Spontaneous recurrent seizures were quantified with 3 week-long continuous video-EEG monitoring. Complement expression and glia activation were studied by immunocytochemistry at 7 days and 4 months post-SE. Result: SE group developed chronic recurrent seizures with a frequency of 0.5 sz/day. No EEG changes were observed in CON or NoSE group. Marked upregulation of complement C3 expression was found in reactive astrocytes in the hippocampus of SE group, but not in NoSE animals. Compared to NoSE group, SE mice had increased ADC and T2 values in the hippocampus corresponding to the areas of astrocyte activation and C3 upregulation. Conclusion: Persistent C3 upregulation following an epileptogenic insult is associated with destabilization of neuronal networks involved in seizure generation and progression of tissue damage.
006 SEVERE FUNCTIONAL DEFECTS OF THE KV7.2 CHANNEL CAUSED BY MUTATIONS ASSOCIATED WITH EPILEPTIC ENCEPHALOPATHIES S. Maljevic*, M. Bock*, G. Orhan*, D. Shepers*, S. Weckhuysen, S. Mandelstam, A. Suls, I. E. Scheffer, P. De Jonghe**, and H. Lerche* *Hertie Institute for Clinical Brain Research, Tuebingen, Germany; University of Antwerp, Antwerp, Belgium; 7Florey Neurosciences Institutes, Austin Health, Melbourne, Australia; University of Antwerp, Wilrijk, Belgium; Royal Children's Hospital, Parkville, VIC, Australia; and **Neurogenetics Group, Antwerp, Belgium
Purpose: Mutations in KCNQ2 and KCNQ3, encoding the voltagegated potassium channels Kv7.2 and Kv7.3, cause Benign Familial Neonatal Seizures (BFNS), an autosomal- dominant epilepsy syndrome with favorable prognosis. However, some KCNQ2 mutations lead to more severe clinical phenotypes, as reported for seven novel KCNQ2 mutations associated with an epileptic encephalopathy (Weckhuysen et al., 2012). In these patients, seizures were extremely refractory, profound intellectual disability was present and the MRI revealed transient T1 and T2 hyperintensities of the basal ganglia and thalamus. To elucidate the mechanisms behind the observed epileptic phenotypes we set out to functionally investigate these mutations. Method: Using site-directed mutagenesis the mutations were inserted into the KCNQ2 cDNA and potassium currents recorded in cRNAinjected Xenopus laevis oocytes, using a fully-automated injection and a two-voltage clamp system. Result: Mutations affecting the pore loop (p.A265P, p.T274M) and S6 segment (p.G290D) yielded barely measurable potassium currents and exhibited a prominent dominant-negative effect on the WT currents of Kv7.2, Kv7.3 or Kv7.2/Kv7.3 channels. A depolarizing shift by about 10 mV (p.I205V) or 60 mV (p.R213Q) was observed for the S4 segment mutants, as well as for the C-terminal mutation p.R532W (~20 mV). The second C-terminal mutation (p.M518V) reduced the maximal current amplitude to one third of the WT. Conclusion: Whereas haploinsufficiency of Kv7.2 presents the major pathomechanism of BFNS with only a few mutations exhibiting a dominant-negative effect, our electrophysiological findings indicate dramatic functional deficits for the majority of the epileptic encephalopathy mutations, which could present a plausible explanation for the more serious clinical phenotype.
008 GABAERGIC INTERNEURONS LEAD TO THE EPILEPTOGENESIS: INTERNEURON PATHOLOGY ASSOCIATED WITH ARX MUTATION M. Itoh*, S. Okazaki, H. Kawawaki, T. Inoue, and Y. Goto* *National Center of Neurology and Psychiatry, Kodaira, Japan; and Osaka City General Hospital, Osaka, Japan
Purpose: X-linked lissencephaly with abnormal genitalia (XLAG), showing severe neonatal seizure and developmental delay, is a rare disorder caused by mutations in the aristaless-related homeobox (ARX) gene, located in Xp22.13. Arx-null mice for human XLAG model showed loss of tangential migration of GABAergic interneurons. However, GABAergic interneuron distribution of XLAG brain has never been reported. In the present study, we investigated subpopulation of GABAergic interneurons in the brain of an infant with XLAG, who had a nonsense mutation of the ARX gene, compared with those of age-matched normal control and Miller-Dieker syndrome. Method: We performed immunocytochemistry for interneuron and migration markers. Result: Glutamic acid decarboxylase (GAD)- and calretinin (CR)-containing cells were significantly very few in the neocortex and, interestingly, located in the white matter and neocortical subventricular zone, while neuropeptide tyrosine and cholecystokinin positive cells were normal. From previous rodent studies, the imbalance of GABAergic interneurons may be derived from the caudal ganglionic eminence tangential migration. Also, in the neocortical subventricular region, the GAD- and CR-containing cells had Mash-1 protein, like a radial migration marker, and nestin protein. Conclusion: ARX protein controls not only tangential migration of GABAergic interneurons from the ganglionic eminence, but also may serve to induce radial migration from the neocortical subventricular zone.
007 COMPLEMENT C3 UPREGULATION CONTRIBUTES TO A SUSTAINED INFLAMMATORY RESPONSE AND PERPETUATION OF SEIZURE FOCI IN A PILOCARPINE MODEL OF TEMPORAL LOBE EPILEPSY I. Kharatishvili, D. She, Z. Shan, N. Kurniawan, and D. Reutens Centre for Advanced Imaging, Brisbane, Qld, Australia
4 Abstracts
Clinical Epileptology Monday, 01 October 2012

009 NEUROLOGICAL AND NEUROIMAGING OUTCOMES OF CHILDHOOD STATUS EPILEPTICUS: A 10-YEAR COHORT STUDY S. Pujar*, M. Martinos*, K. Chong, B. Neville*, R. Scott*, and R. Chin* *UCL Institute of Child Health, London, UK; and Great Ormond Street Hospital for Children NHS Trust, London, UK
Purpose: The long-term outcome following childhood convulsive status epilepticus (CSE) is uncertain. We report preliminary data on neurological and neuroimaging outcomes within 10 years of CSE from a prospective paediatric population-based study. Method: Enrolled children were invited to have clinical neurological evaluation and brain MR Imaging (MRI) on a 1.5T scanner. An experienced paediatric neuroradiologist qualitatively assessed all MRIs. Result: 72 children (33 male) have been investigated. Median follow-up 7.9 years. 49 had both clinical assessment and MRI. 20 had prolonged febrile seizures (PFS), 8 acute symptomatic (AS), 11 remote symptomatic (RS), 6 idiopathic, and 4 unclassified CSE. At follow-up, all children with PFS were neurologically normal and none had epilepsy. One with AS CSE (12%) developed epilepsy that remitted after 2 years. All with RS CSE, except two, had active epilepsy, and significant neurological impairments. None with idiopathic and unclassified CSE had epilepsy or neurological impairments except two (33%). Only one child (5%) in PFS group had abnormal MRI: unilateral reduction in hippocampal volume. Amongst AS CSE, 4 (50%) had normal MRI, 3 (37%) abnormalities unlikely to be clinically significant, and 1 (12%) had left mesial temporal sclerosis (MTS). The child with MTS had only one episode of CSE with meningitis and no further seizures. 8 children (73%) with RS CSE had abnormal MRIs. All children with idiopathic and unclassified CSE had normal MRI. Conclusion: Children without prior neurological insult and/or epilepsy have good neurological outcome within 10 years of CSE. Significance of the hippocampal abnormalities in three children without a clinical correlate is uncertain.
in 43/119 (36.1%), remote symptomatic in 49/119 (41.2%) and progressive symptomatic in 24/119 (20.2%) patients. In acute and remote symptomatic aetiology, the most common reasons were cerebrovascular diseases (14/119; 11.8% vs. 27/119; 22.7%), while in progressive symptomatic aetiology brain tumors (8/119; 6.7%) were the most frequent cause. 70/119 (58.5%) patients suffered from epilepsies before admission to the NICU. Conclusion: About a sixth of patients admitted to the NICU had SE or SZs. Aetiology was symptomatic in most of the cases. The main reasons for acute and remote symptomatic SE or SZs were cerebrovascular diseases. Approximately two fifth of the patients had new-onset SZs or SE.
011 MIDDLE SHORT GYRUS OF THE INSULA IMPLICATED IN SPEECH PRODUCTION: INTRACEREBRAL ELECTRIC STIMULATION OF PATIENTS WITH EPILEPSY A. Afif, L. Minotti, P. Kahane, and D. Hoffmann Neurological Hospital, Hospices Civils de Lyon, Lyon, France
Purpose: The data of this study suggests the involvement of the upper middle short gyrus in speech production. Method: 25 patients suffering from severe drug refractory partial epilepsy were investigated by stereo-electroencephalography (SEEG). At least one electrode explore the insula using an oblique approach (transfrontal or trans-parietal). 313 stimulations were performed in 27 insula. 83 responses induced by insular electrical stimulation (ES), eight (9.6%) were reported by five patients as speech arrest (5 responses) and a lowering of voice intensity (3 responses). The stereotactic approach allows us to identify the stimulation sites within the insula in terms of its gyri. Also, the stimulation sites were anatomically localized via image fusion between pre-implantation 3D MRI and post-implantation 3D CT scans revealing the electrode contacts. Result: 8 responses were reported as speech disturbances. 7 among them were evoked by stimulation in the middle short gyrus (25.9% of responses evoked in the middle short gyrus). The site of the 8th response was in the post-central insular gyrus in the same insular region where the oropharyngeal responses induced by other ES (pharyngeal construction) in this study. The data suggest the involvement of the middle short gyrus of the insula in the procedures of language. Conclusion: This study provides evidence that the middle short gyrus of the insula responds to ES producing speech disturbances. These results are the first to report language disorders in humans evoked by electrical stimulation of the insular cortex during SEEG explorations in terms of gyral anatomy.
010 ASSESSMENT OF STATUS EPILEPTICUS AND SEIZURES IN NEUROLOGICAL INTENSIVE CARE UNIT IN SALZBURG, AUSTRIA J. Dobesberger, A. Arkhundova, H. Novak, A. Zerbs, T. Moroder, J. Hfler, M. Leitinger, C. A. Granbichler, and E. Trinka Paracelsus Medical University, Salzburg, Austria
Purpose: Status epilepticus (SE) as well as aggravation of epileptic seizures (SZs) are common reasons for admission to a neurological intensive care unit (NICU). They may also occur as complications during the stay in patients at the NICU. The aim of this study was to evaluate incidence and clinical data of SE and SZs at a NICU. Method: We retrospectively analysed all consecutive patients who were admitted to the NICU of the Department of Neurology, Paracelsus Medical University, in Salzburg, Austria, between from January 2010 to May 2011. Result: A total of 719 patients were admitted to the NICU, 121/719 (16.8%) patients (68 men; mean age 59.0 19.6 years; range 1491) had SE or SZs: 84/121 (69.4%) had the referral diagnosis SE, 32/121 (25.5%) SZs and 5/121 (4.1%) developed SE or SZs during the stay. 116/119 (97.5%) patients had symptomatic aetiology: acute symptomatic
012 ASPECTS OF ICTAL CONSCIOUSNESS IN PATIENTS WITH EPILEPSY, NON-EPILEPTIC ATTACK DISORDER (NEAD) AND DUAL DIAGNOSIS A. E. Cavanna, and F. Ali Birmingham and Solihull Mental Health NHS Foundation Trust, Birmingham, UK
Purpose: Self-report measures of ictal consciousness suggest greater levels of awareness and subjective experiences in patients with NEAD compared to epilepsy. This study further investigated which specific aspects of consciousness alterations show most variability across seizure types. Method: A total of 77 adult out-patients (n=21 with a diagnosis of epilepsy, n=38 with NEAD and n=17 with a dual diagnosis) were recruited
5 Abstracts
from the specialist Neuropsychiatry Clinic at BSMHFT/University of Birmingham. All participants completed a standardised battery of psychometric measures, including the 20-item Ictal Consciousness Inventory (ICI). This instrument allows investigation of the level of awareness (ICI-level: items 110) and subjective consciousness experiences (ICIcontent: items 1120) during recalled seizures and non-epileptic attacks. Result: Item-by-item comparison revealed a statistically significant difference in Item 20, which captures the presence and vividness of ictal emotions (Kruskall-Wallis test, p=0.05; epilepsy mean score=3.6; NEAD= 4.2; dual diagnosis=3.3). Trends towards statistical significance were also demonstrated for Item 17, which assesses metamorphopsia (p=0.08; dual diagnosis mean score=4.2; epilepsy=3.3; NEAD=4.0) and Item 18, which assesses mnestic dysperceptions (p=0.09; epilepsy mean score=3.2; NEAD=4.0; dual diagnosis=4.2). Conclusion: The results of the present study are in accordance with previous findings, emphasizing the more florid interpretation of ictal experiences in patients with NEAD. This is particularly evident in items assessing the presence of positive ictal emotions, metamorphopsia and memory flashbacks, suggesting a possible role for dysregulation in the emotional processing of perceptual experiences in the pathophysiology of NEAD.
014 PSYCHIATRIC COMORBIDITY IN CHILDREN BEFORE AND AFTER TEMPORAL LOBE EPILEPSY SURGERY A. Michoulas*, C. Waisburg, S. J. Akdag, A. Chapman, and M. B. Connolly* *University of British Columbia, BC Children's Hospital, Vancouver, Canada; Institue of Neurosciences, Favaloro University, Buenos Aires, Argentina; BC Children's Hospital, Vancouver, Canada; and University of British Columbia, BC Children's Hospital, Vancouver, Canada
Purpose: The primary objective of this study was to establish the rate and types of psychiatric comorbidities among children with temporal lobe epilepsy before and after epilepsy surgery. The secondary objective was to examine for predictors of psychiatric comorbidity. Method: All pediatric patients who underwent temporal lobe epilepsy surgery at British Columbia Children's Hospital between 1995 and 2010, with a minimum 12 month follow-up were included. Sixty-three charts were retrospectively reviewed. Patients undergo multidisciplinary evaluation including screening and referral for psychiatric symptoms. Psychiatric disorders included: attention-deficit/hyperactivity disorder (ADHD), emotional disorder (depression and/or anxiety), pervasive developmental disorder (PDD), obsessive-compulsive disorder and psychosis. Result: Psychopathology was diagnosed in 26 (44.4%) patients preoperatively and in 31 (49.2%) patients post-operatively. The most common were emotional disorder (27% pre-operative and 36% post-operative) and ADHD (26% pre-operative and 20% post-operative). Notably, 58% of patients with an emotional disorder received psychological and/ or medical therapy. Five of 17 (29.4%) patients with depression had suicidal ideation. Pre-operative ADHD was significantly more common in patients with a family history of psychiatric illness (p=0.002). Pre-operative psychiatric comorbidity was a significant predictor of post-operative psychiatric comorbidity, p=0.006. No relationship was found between duration of epilepsy, pathology, seizure outcome and psychiatric diagnosis. Conclusion: Psychiatric comorbidity is common in pediatric temporal lobe epilepsy. Temporal lobe surgery did not influence the occurrence of post-operative psychopathology. Children with a pre-operative psychiatric comorbidity were significantly more likely to have a post-operative psychiatric comorbidity. Psychiatric assessment and treatment are important components of epilepsy surgery care.
Neuropsychiatry Monday, 01 October 2012

013 POSTICTAL PSYCHOSIS IN TEMPORAL LOBE EPILEPSY RISK FACTORS AND POSTSURGICAL OUTCOME R. A. Cleary*, P. J. Thompson*, and J. Foong *The National Hospital for Neurology and Neurosurgery and Institute of Neurology, London, UK; and The National Hospital for Neurology and Neurosurgery, London, UK
Purpose: Postictal psychosis (PIP) reportedly occurs in 410% of patients with temporal lobe epilepsy (TLE). Whilst the clinical characteristics are well described, less is known about the pathophysiological mechanisms and predisposing factors. The aims of this study were to identify risk factors that may predispose patients to developing PIP and to determine whether a history of PIP predicts postsurgical outcome. Method: We identified 20 patients with a history of PIP-TLE from a total of 280 TLE patients on the epilepsy surgery database at the National Hospital for Neurology and Neurosurgery, London. They were compared to 60 age-matched TLE patients without any psychiatric history, with respect to presurgical clinical and neuropsychological variables. Group differences in postsurgical psychiatric, cognitive and seizure outcomes over 4 years were also examined. Result: Our current analysis indicated that PIP-TLE patients were less likely to have localised interictal and ictal EEG abnormalities than the TLE controls, particularly regarding ictal EEGs. Other presurgical clinical and neuropsychological variables did not distinguish between the groups. PIP-TLE patients were more likely to develop postsurgical psychiatric disorders (p=0.018) within 4 years of surgery but there were no differences in seizure or cognitive outcomes. Conclusion: Our results suggest that more widespread or diffuse brain abnormalities as reflected by EEG findings may contribute to the development of PIP. Furthermore, patients with a history of PIP who undergo epilepsy surgery have an increased risk of developing postsurgical psychiatric disorders. This has implications for presurgical counselling and also highlights a need for postsurgical psychiatric monitoring for these patients.
015 HOW SODIUM VALPROATE CAUSES LANGUAGE DELAY AND AUTISM - A MOLECULAR STUDY R. Moldrich, G. Leanage, and D. Reutens University of Queensland, Brisbane, Qld, Australia
Purpose: The widely used anti-epileptic drug sodium valproate (VPA) vastly increases the risk of autism spectrum disorders (ASD) upon prenatal exposure. Our aim was to test the hypothesis that VPA is causing ASD via inhibition of histone deacetylase (HDAC) using a mouse model of in utero VPA exposure. Method: We created an mouse model of autism prenatally exposed to VPA (600mg/kg) at embryonic day 12 and compared it to an animal prenatally exposed to a specific HDAC inhibitor, trichostatin A (TSA) (1mg/kg). We measured HDAC enzyme activity, histone acetylation status and behavioural features in juvenile mice. Result: Treatments with 600 mg/kg VPA and 1 mg/kg TSA reduced HDAC enzyme activity to activity to 60% and 63% of control, respectively. We also measured acetylated histone levels by SDS-PAGE and
6 Abstracts
Western blot. We found that 600 mg/kg VPA, 200 mg/kg VPA and 1 mg/ kg TSA similarly increased acetylated histone H4, but not H3 levels to approximately 200% of control. Postnatally, 600 mg/kg VPA and 1 mg/ kg TSA treated mice demonstrated a similar lack of olfactory motivation, delayed motor ability and sociability deficits, analogous to deficits seen in infants with autism. Conclusion: Pharmacological or environmental inhibition of HDAC can lead to subtle morphological changes in the developing embryo, leading to ASD-like behavioural manifestations. Further, HDAC inhibition in embryos is likely the cause of developmental delay following VPA administration during pregnancy. Purpose: The aim of the study was analysis of efficiency and safety of oxcarbazepine at children and adults depending on patient's age and forms of epilepsy. Method: 155 patients receiving oxcarbazepine (male = 78, female = 77) of the age from 5 month till 59 years are observed in dynamics with video-EEG control at the period 20062011. Were identified: IGE with isolated GTCS 5, focal frontal lobe epilepsy 40, temporal lobe 63, parietal lobe 6, occipital lobe 13, idiopathic focal 5, epileptic encephalopathies 23 patients. Result: Oxcarbazepine was effective at 59.3% of patients (n=92), and among the patient at monotherapy effectiveness (68.5%, at 37 from 54 patients) was higher than in combined therapy (54.4% at 55 of 101 patients). Low efficiency was seen at 29.1% (n=45) patients. The aggravation effect has been noted at 11.6% (n=18) of patients. Drug compliance (for >1 year) was 56.8% (n=88). High efficiency in group <1 year (n=14) was 35.7% (n=5), low 35.7% (n=5), aggravation 28.6% (n=4); in group 13 years (n=24) high efficiency 37.5% (n=9), low 37.5% (n=9), aggravation 25% (n=6); in pediatric population >3 years (n=78) high efficiency 62.8% (n=49), low effect in 29.5% (n=23), and 7.7% aggravation (n=6), in adult population >18 years (n=39) the efficiency was 74.4% (n=29), low effect 20.5% (n=8) and aggravation in 5.1% (n=2). Conclusion: Oxcarbazepine is highly effective drug in therapy of IGE with isolated GTCS, in symptomatic focal forms and Panayiotopoulos syndrome. With increasing of patients age the efficiency of oxcarbazepine raises, while aggravation risks decrease.
016 PREVALENCE AND ASSOCIATES OF SUICIDAL BEHAVIOR IN FREQUENT TREATMENT-RESISTANT FOCAL SEIZURES: THE ASERT STUDY J. French*, D. Hesdorffer, K. Posner, B. Diventura*, J. Pollard, M. Sperling, C. Harden, G. L. Krauss**, and A. M. Kanner *New York University Comprehensive Epilepsy Center, New York, NY, USA; Columbia University, New York, NY, USA; University of Pennysilvania, Philadelphia; Thomas Jefferson University, Philadelphia; Long Island Jewish Medical Center, North Shore; **Johns Hopkins University, 21287 USA; and Rush Medical College, Chicago, USA
Purpose: To assess lifetime suicidal ideation (SI) and behavior (SB), and their associates in treatment-resistant focal seizures. Method: A mulitcenter, cross-sectional study at 6 epilepsy centers. Inclusion criteria were: 1870 years; EEG-confirmed focal epilepsy for >2 years; >1 simple partial (with motor component), complex partial/secondarily generalized seizure per month for the past 6 months; currently taking 13 AEDs; and failed >2 AEDS, including current therapy. Columbia Suicide Severity Rating Scale assessed SI/SB. MINI assessed major depression (MD). High risk SI included intent/intent and plan. SB included suicide attempt (SA), interrupted or aborted attempt, preparatory acts/behavior, and non-suicidal self-injurious behavior. Calculated frequency of lifetime SI/SB. Logistic regression examined demographic, seizure-related and psychiatric correlates of suicidality. Result: 95 of 206 participants (46.1%) had lifetime SI, 29 (14.1%) had high risk SI, 21 (10.2%) had SA and 21 (10.2%) had SB without SA. No demographic or seizure-related factors were associated with SI or SB. Lifetime MD was significantly associated with lifetime SI (OR=10.8), high risk SI (OR=4.7), SA (OR=4.7) and SB without SA (OR=4.9). Conclusion: SB without SA is as common as SA alone in treatmentresistant focal seizures. Only lifetime MD is associated with SI/SB. Prevention of SB in epilepsy requires identification of lifetime MD in order to counsel and offer treatment.
018 DISCONTINUATION OF ANTIEPILEPTIC DRUGS IN PREGNANCY: A UK POPULATION BASED STUDY IN THE HEALTH IMPROVEMENT NETWORK PRIMARY CARE DATABASE S. Man*, I. Petersen*, M. Thompson, and I. Nazareth* *University College London, London, UK; and Cegedim Strategic Data, London, UK
Purpose: Antiepileptic drugs (AEDs) control seizures, which is a priority in pregnancy to prevent harm to the mother and fetus. However, AEDs are associated with increased risk of congenital malformations. We examined the discontinuation of AED prescribing in pregnant women using UK primary care data from The Health Improvement Network. Method: In total, 174,055 pregnant women were identified aged 13 55 years of which 745 were prescribed AEDs for epilepsy in the three months before pregnancy. Time to the last consecutive AED prescription before delivery was estimated and comparisons made to non-pregnant women with epilepsy, using Cox's regression. Factors predicting discontinuation of AEDs amongst pregnant women were investigated. Result: Pregnant women with epilepsy were twice as likely to cease AEDs compared to non-pregnant women (Hazard Ratio (HR):2.00, 95% confidence interval (CI):1.622.47). Of 745 women, 601 (80.7%) continued treatment into pregnancy and 465 (62.4%) to the end of the second trimester. Of 1490 non-pregnant women with epilepsy, 1242 (83.4%) and 1071 (71.9%) continued for comparable time periods. Compared to pregnant women with more than one AED prescribed in 36 months before pregnancy, women with one prescription were more likely to cease treatment (HR: 3.31, 95% CI: 2.574.23), whilst those with no prior prescriptions were at an even higher risk (HR: 6.32, 95% CI: 4.578.73). Conclusion: Pregnancy is a determinant for the discontinuation of AED prescribing amongst women with epilepsy, despite the possible grave consequences of uncontrolled seizures in pregnancy. Women with little exposure to AEDs prior to pregnancy should be monitored closely to ensure they do not abruptly cease medication.
Antiepileptic Drugs Monday, 01 October 2012

017 ANALYSIS OF EFFICIENCY AND SAFETY OF OXCARBAZEPINE DEPENDING ON PATIENT'S AGE AND FORMS OF EPILEPSY A. A. Kholin*, E. S. Il`Ina, and N. N. Zavadenko* *Russian State Medical University, Moscow, Russian Federation; and Russian Children Clinical Hospital, Moscow, Russian Federation
7 Abstracts
019 TOLERABILITY AND SAFETY OF ZONISAMIDE IN ELDERLY PATIENTS WITH PARTIAL EPILEPSY: RESULTS OF A POOLED ANALYSIS E. Trinka*, J. Segieth, and L. Giorgi *Paracelsus Medical University, Salzburg, Austria; and Eisai Limited, Hatfield, UK
Purpose: To assess the tolerability/safety of zonisamide in elderly patients with partial epilepsy. Method: A pooled analysis of data from elderly (65 years) patients receiving zonisamide for partial seizures in clinical studies was conducted (N=95) and compared to pooled adult (1865 years) patient data (N=1389). Assessments included treatment-emergent adverse events (TEAEs), clinical laboratory parameters and weight. Result: Overall incidence of TEAEs was similar in elderly versus adult patients (82.1% vs. 83.9%). Incidence was lower in elderly versus adult patients for treatment-related TEAEs (55.8% vs. 72.7%), severe TEAEs (11.6% vs. 20.4%), serious TEAEs (12.6% vs. 16.6%), and TEAEs leading to withdrawal (17.9% vs. 22.1%). TEAEs reported by 5% of patients in either cohort and more frequently by elderly versus adult patients were fatigue (11.6% vs. 9.7%), nasopharyngitis (8.4% vs. 7.2%), constipation (7.4% vs. 4.8%) and pruritus (6.3% vs. 2.1%). Serious TEAEs reported by >2% elderly patients were convulsion (2.1%) and grand mal convulsion (2.1%). Three elderly patients died but only one death was considered treatment-related (circulatory collapse following pancreatitis). No severe TEAEs were reported by >2% elderly patients. For elderly patients, there were few clinically significant changes in clinical laboratory parameters, no reports of respiratory alkalosis or metabolic acidosis, and no significant weight changes. Conclusion: Zonisamide was well tolerated by elderly patients with partial epilepsy when compared to adult patients. Most TEAEs were of mild-to-moderate intensity and the overall incidence was similar to adult patients. No new or unexpected safety findings were identified. Supported by Eisai 3 years exposure was due to premature discontinuations and study completion because of the commercial availability of lacosamide. For 1-year, 2-year, 3-year, 4-year and 5-year completers, the median percent seizure frequency reduction from Baseline was 59.4%, 64.1%, 67.9%, 69.3% and 71.0%; the 50% responder rate was 60.2%, 65.9%, 68.0%, 72.6% and 70.2%. A total of 81.3% of patients reported 1 treatment-emergent adverse event, most commonly (10%) dizziness (21.5%), headache (14.0%), and nasopharyngitis (10.7%). Conclusion: Used in the approved dose range (up to 400mg/day), longterm adjunctive lacosamide provided sustained efficacy and was well tolerated in adults with POS. These subanalysis results are consistent with those for the entire OLE population. UCB-sponsored.
Clinical Pharmacology and Therapeutics Tuesday, 02 October 2012

021 ANTIEPILEPTIC DRUGS AND LIPID METABOLISM: VALPROATE NOT SO INNOCENT? I. Y. Tan, H. Hegge, M. Majoie, P. Verschuure, C. Vader, and M. Veendrick Kempenhaeghe, Heeze, The Netherlands
Purpose: Following the hypothesis that Antiepileptic Drugs (AED) influence lipid metabolism via the cytochrome P450 system, we studied the relation between drugload of enzyme-inducers (IND_AED) and enzyme-inhibitors (INH_AED) on the one hand and lipid fractions on the other hand in adult patients with polytherapy. Method: Blood samples were collected from 261 resident patients of an epilepsy center, who all had epilepsy and (intellectual) disability. Patients with interfering medication were excluded. Patients were grouped according to use of IND_AED (87 patients with carbamazepine, phenytoin and/or phenobarbital) or INH_AED (20 patients using valproate). Enzyme-neutral comedication was allowed. Assessment was done for lipid metabolism, including Cholesterol, High-density lipoproteins (HDL), Low-density lipoproteins (LDL), triglycerides (TG) and Total Cholesterol (TC). Drug load was computed by summing PDD/DDDs (Prescribed daily dose/defined daily dose) for AED in the same enzyme-group. Result: Not surprisingly, IND_AED correlated with higher levels of serum lipids LDL, HDL, TG and TC. This is consistent with evidence from literature. Higher drugload of IND_AED correlated with higher lipid fractions, but this effect just failed to reach statistic significance. Remarkably, INH_AED correlated with elevated levels of TG, which to our knowledge is a novel finding. Moreover, there was a statistic significant relation between drugload of INH_AED and TG and TC/HDL ratio. A possible explanation for this phenomenon is that the elevated TG levels are an expression of a metabolic syndrome, related to VPA. A remarkable anecdotic finding was that in one of the patients on valproate the TG level decreased considerably after discontinuing valproate.
020 LONG-TERM TREATMENT WITH ADJUNCTIVE LACOSAMIDE FOR PARTIAL-ONSET SEIZURES: AN ANALYSIS OF RESULTS FROM PATIENTS EXPOSED ONLY TO APPROVED DOSES N. Dcruz*, P. Doty*, C. Mcshea*, S. Dimova, and M. De Backer *UCB, Raleigh, USA; UCB Pharma, Brussels, Belgium; and UCB, Brussels, Belgium
Purpose: To evaluate long-term efficacy and tolerability of adjunctive lacosamide in adults with partial-onset seizures (POS) who received lacosamide doses within the approved dose range (400mg/day). Method: Data were pooled from three long-term, open-label extension trials (OLE; NCT00552305; NCT00522275; NCT00515619) in adults with POS who had completed one of three double-blind, placebo-controlled Phase II/III trials of adjunctive lacosamide. During OLE treatment, dosage adjustments of lacosamide (100800mg/day) and/or concomitant AEDs were allowed to optimize tolerability and seizure control. This subanalysis evaluates trial outcomes during the extension study for patients exposed to 400mg/day lacosamide during both double-blind and open-label treatment. Result: Of 1,054 patients who initiated open-label lacosamide treatment, 363 (34.4%) had been exposed only to lacosamide doses 400mg/ day. Patients exposed to 400mg/day lacosamide for >1, >2, >3, >4 and >5 years was 64.2%, 50.1%, 41.0%, 34.2%, and 15.7%; the decrease after
022 DOES CARBAMAZEPINE AFFECT THE QT INTERVAL? T. Yadee, and K. Unnwongse Prasat Neurological Institute, Bangkok, Thailand
Purpose: Pathologic cardiac repolarization may occur during seizures and has been linked to SUDEP. In this retrospective case control study, we investigated if Carbamazepine affects the QTc interval.
8 Abstracts
Method: Nineteen patients with epilepsy on Carbamazepine were matched for age and sex to 19 patients on Carbamazepine for neuralgia or mood disorders and 19 patients admitted for elective surgeries who were not taking Carbamazepine. None of the patients had concomitant cardiovascular disease or were taking medications known to affect the QTc interval. QTc intervals and Carbamazepine doses and blood levels, were analyzed using one-way ANOVA. Result: Two out of 19 patients (11%) in the epilepsy group but none in other groups had QTc prolongation (>450 milliseconds). The mean QTc interval was longer in patients taking Carbamazepine for epilepsy, compared to both patients taking Carbamazepine for other reasons and patients without epilepsy not taking Carbamazepine (41726 vs 40017 vs 40316 milliseconds) (p=0.029). Mean dose and blood level of Carbamazepine in epilepsy and non-epilepsy groups did not differ (737389vs 716407 mg/d and 7.272.46vs 7.362.65 mg/dl) (p=0.87 and p=0.92). Conclusion: Carbamazepine may lead to QTc prolongation in patients with epilepsy but not in other neurologic disorders. A longitudinal study comparing QTc intervals before and after treatment with Carbamazepine is required to confirm this finding. Method: All outpatients who initiated treatment with ESL between 01/ 04/2010 and 31/03/2011 were included. We retrospectively collected data on demographics, clinical features, treatment response, compliance and side effects. Only patients with at least one follow-up (FU) visit were included in the safety analysis, and only those with 1 year follow-up were included in the effectiveness analysis. Result: We included 113 patients (58$), mean age 39yo (776), mean epilepsy duration 27.2 years (250) and mean seizure frequency 27/ month (0600); 57.5% were taking 2 AED and the remaining 3 AEDs. At the last FU visit (n=110), 71.8% were still on treatment [median dosage 1200mg (4001600)]. Therapy discontinuation was mainly due to side effects (17.7%) or lack of efficacy (7.1%). About 49% of patients (n=56) had 1 year follow-up. From these, 38.2% were responders (50% reduction in seizure frequency); 39.3% were greatly improved or seizure free (clinician global impression-CGI). Effectiveness was higher in patients treated with 2 AEDs vs 3 AEDs (Responder rate - 46.7% vs 28.0%, p=0.254; CGI - 51.6% vs 24.0%, p=0.068). Conclusion: In a one year FU, ESL was effective in a significant proportion of patients particularly in those with less refractory epilepsy. ESL was well tolerated, with few patients discontinuing drug due to side effects, none of which severe.
023 CHANGED CONSTITUTION WITHOUT CHANGE IN BRAND NAME - THE RISK OF GENERICS IN EPILEPSY V. I. Patel, D. J. Cordato, M. Dias, and R. G. Beran Liverpool Hospital, Liverpool, NSW, Australia
Purpose: Lamotrigine (LTG) is an Anti Epileptic Medication (AEM) for which blood levels are helpful for optimal dosing. In late 2010, patients attending an epilepsy clinic were becoming toxic without obvious cause. This paper reports altered levels without change in regimen and provides unexpected findings. Method: Patients with elevated LTG blood levels were assessed to determine change in AEM regimen or generic substitution. Method of blood level determination was reviewed and the company (GlaxoSmithKline) contacted regarding change in source of medication. Result: The sample comprised 18 patients; mean age 40 16 years, mean daily LTG dose 493 218 mg. Mean serum LTG concentrations from August 2010 to February 2011 [91.817.7 lmol L-1, range 69.9 133.7 lmol L-1] were significantly higher than those from January 2010 to July 2010 [50.39.1lmol L-1, range 3260.1 lmol L-1), p < 0.0001]. All patients received parent product (Lamictal) and the method of LTG blood level determination was unchanged. GlaxoSmithKline confirmed that Lamictal was sourced from a different site. Conclusion: These results indicate that, even using a parent compound, AEM levels can fluctuate if the product source has changed, resulting in toxicity. It also highlights the value of determining AEM levels and the risks attached to generic substitution.
Genetics 2 Tuesday, 02 October 2012

025 PRRT2 LINKS INFANTILE CONVULSIONS AND PAROXYSMAL DYSKINESIA WITH MIGRAINE R. Cloarec*, N. Bruneau*, G. Rudolf, A. Massacrier*, M. Salmi*, M. Bataillard, C. Boulay, R. Caraballo, N. Fejerman, P. Genton*, E. Hirsch, A. Hunter, G. Lesca, J. Motte**, A. Roubertie, D. Sanlaville, S. W. Wong, Y. Fu, J. Rochette, L. Ptacek, and P. Szepetowski* *INSERM U901 - INMED, Marseille, France; Strasbourg University Hospital, Strasbourg, France; Juan P. Garrahan Pediatric Hospital, Buenos Aires, Argentina; Children's Hospital of Eastern Ontario, Ottawa, Canada; University Hospital of Lyon, Bron, France; **American Memorial Hospital, Reims University Hospital, Reims, France; Montpellier, France; Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia; University of California San Francisco, San Francisco, USA; and Universit de Picardie Jules Verne, Amiens, France
Purpose: Whole genome sequencing and the screening of 103 families recently led us to identify PRRT2 (proline-rich transmembrane protein) as the gene causing autosomal dominant infantile convulsions (IC) with paroxysmal kinesigenic dyskinesia (PKD) (PKD/IC syndrome, formerly ICCA). There is inter- and intra-familial variability and the patients may present with IC and/or PKD. In order to explore the mutational and clinical spectra, additional cases and families with either typical PKD/IC or PKD/IC with migraine were analyzed. Method: Sanger sequencing of all PRRT2 coding exons and of exonintron boundaries was performed in the probands and in their relatives whenever appropriate. Result: PRRT2 mutations were detected in 18 of 34 families. The p.R217Pfs*8 recurrent mutation and a novel frameshift mutation (p.R145Gfs*31), were found in 50% of typical PKD/IC. In another family, p.R217Pfs*8 cosegregated with PKD associated with hemiplegic migraine (HM). p.R217Pfs*8 was also detected in one IC patient having migraine with visual aura and speech difficulties, and in related PKD/IC familial cases having migraine without aura. p.R217Pfs*8 was also detected in one sporadic case with complex migrainous disorder. The pre-
024 ONE YEAR FOLLOW-UP EXPERIENCE WITH ESLICARBAZEPINE ACETATE (ZEBINIX) IN A TERTIARY HOSPITAL IN OPORTO, PORTUGAL F. D. Correia, J. P. Domingos, J. G. Freitas, R. Loureiro, J. Lopes, J. Ramalheira, J. Chaves, and J. Lopes-Lima Hospital de Santo Antnio, Centro Hospitalar do Porto, Porto, Portugal
Purpose: Introduction: Eslicarbazepine acetate (ESL) is a new antiepileptic drug available in Portugal since April 1st 2010. Despite good safety and efficacy shown in clinical trials, little is known about its effectiveness in clinical practice. Objective: Assess one year follow-up post-commercialization experience
9 Abstracts
viously reported p.R240X mutation was found in one PKD patient with migraine without aura. A novel frameshift mutation (p.S248Afs*65) was identified in a PKD/IC family member with IC and migraine with visual and aphasic aura. Conclusion: Taken together, our data extend the spectrum of PRRT2 mutations and phenotypes to HM and to other types of migraine in the context of PKD/IC, and emphasize the phenotypic pleiotropy seen with PRRT2 mutations.
*University of Oxford, Oxford, UK; Oxford University NHS Trust, Oxford, UK; Leicester Royal Infirmary, Leicester, UK; and Imperial College, London, UK
Purpose: To assess the frequency and clinical features of childhood onset intractable epilepsy caused by the most common mutations in the POLG1 gene which encodes coding for the catalytic subunit of mitochondrial DNA polymerase gamma. Method: Children presenting with non-syndromic intractable epilepsy of unknown aetiology, but without documented liver dysfunction at presentation were eligible for the prospective, population-based study. The blood samples were analysed for the three common POLG1 mutations. If some of the three tested mutations were found, all the exons and the exon-intron boundaries of the POLG1 gene were sequenced. In addition we retrospectively reviewed the notes of patients presenting with intractable epilepsy in whom we had found POLG1 mutations. All available clinical data was collected by questionnaire and by reviewing the medical records. Result: We analysed 213 blood DNA samples from patients fulfilling the inclusion criteria of the prospective study. Among these, four patients (1.9%) were found with one of the three common POLG1 mutations as homozygous or compound heterozygous states. In addition, three patients were retrospectively identified. Six out of seven patients had either raised CSF lactate or brain MRI changes at the presentation of intractable epilepsy. Two of the three patients who later developed liver dysfunction died. Conclusion: We recommend POLG1 gene testing for patients with intractable seizures and 1 raised CSF lactate or suggestive brain MRI changes (with thalamic predominance) with or without status epilepticus, epilepsia partialis continua or liver manifestations typical for Alpers disease, especially when the disease course is progressive.
026 THE FAMILIAL EPILEPSY SYNDROME OF GENETIC EPILEPSY WITH FEBRILE SEIZURES PLUS: SYNDROME EVOLUTION OVER SEVENTEEN YEARS I. E. Scheffer*, J. P. Malone, G. C. Glubb, K. Helbig, L. Dibbens, L. Vadlamudi, A. Bleasel, R. Burgess, B. Grinton, D. Vears, Z. Afawi, H. Goldberg-Stern**, S. Kivity**, A. D. Korczyn, J. Mulley, S. Berkovic, and Y. H. Zhang *Royal Children's Hospital, Parkville, Vic., Australia; University of Melbourne, Melbourne, Vic., Australia; Women's and Children's Hospital, North Adelaide, SA, Australia; Westmead Hospital, Westmead, NSW, Australia; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; **Schneider Children's Medical Center of Israel, Petach Tikva, Israel; and University of Adelaide, Thebarton, SA, Australia
Purpose: GEFS+ (generalised epilepsy with febrile seizures plus) is a familial epilepsy syndrome characterized by phenotypic heterogeneity that we described in 1997. The GEFS+ spectrum includes Febrile Seizures (FS), Febrile Seizures Plus (FS+), FS/FS+ with generalised and focal seizures, and a range of epileptic encephalopathies including Dravet syndrome and epilepsy with myoclonic-atonic seizures. GEFS+ is associated with mutations of sodium channel and GABA receptor subunit genes; in addition, susceptibility genes have been identified in smaller families. We studied 31 new families and analysed the phenotypic spectrum in these families and our previously published families. Method: We performed detailed electro-clinical phenotyping on all available affected family members and reviewed EEG and neuroimaging studies. We reported the phenotypic findings on 408 affected individuals in a total of 60 families. Result: New phenotypes in GEFS+ families included focal seizures without preceding FS, classical genetic generalised epilepsies and afebrile generalised tonic-clonic seizures. FS remains the most frequent phenotype in GEFS+ followed by FS+. Large GEFS+ families are suggestive of autosomal dominant inheritance. Many smaller families exist where the inheritance pattern is more suggestive of complex inheritance. Conclusion: We suggest that GEFS+ should be renamed genetic epilepsy with febrile seizures plus in view of the significant number of individuals with focal epilepsies. The overlap between GEFS+ and the classical genetic generalised epilepsies is considerably greater than first thought and suggests that the two major groups of generalised epilepsies have shared genetic determinants.
028 INFLAMMATORY PROCESS AND MESIAL TEMPORAL LOBE EPILEPSY WITH EPILEPSY: THE ROLE OF IL-1b J. Chaves*, C. Brito, B. Leal, C. Carvalho, A. Bettencourt, R. Branco, A. Martins Da Silva, P. P. Costa, and B. Martins Da Silva *Hospital de Santo Antnio, Centro Hospitalar do Porto, Porto, Portugal; and Instituto Cincias Biomdicas Abel Salazar, Porto, Portugal
Purpose: Neuroinflammation appears as an important epileptogenic mechanism. Evidence from animal models demonstrated a rapid-onset inflammatory response to acute seizures involving interleukin-1b (IL1b). It was reported that a polymorphism (-511 T>C) in the promoter region of IL-1b gene leads to a higher protein production. The -511T allele has been well accepted as associated with Febrile Seizures (FS) nevertheless the association with Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis (MTLE-HS) development is still controversial. In this study we proposed to analyse the association between -511T>C polymorphism and the development and clinical features of MTLE-HS in a cohort of Portuguese population. Method: Ninety-four MTLE-HS patients (49F, 45M, mean age=39.1610.21 years, 49 with FS antecedents), 95 patients with other focal epilepsies (OEF) and 217 healthy controls were studied. Genotyping was performed using Taqman Real Time PCR methodology. Result: The -511T allele frequency was higher in MTLE-HS when compared to controls (39% vs. 32%, p=0.06 OR=1.40 [0.992.00]). Considering the antecedents of FS we constitute 2 MTLE-HS sub-groups and no differences in -511T>C allelic or genotypic frequencies were found. There were no differences between the OEF group and controls or MTLE-HS patients.
027 PROSPECTIVE STUDY OF POLG1 MUTATIONS PRESENTING IN CHILDREN WITH INTRACTABLE EPILEPSY-PREVALENCE AND CLINICAL FEATURES J. Uusimaa*, J. Poulton*, V. Gowda, T. Mcshane, C. Smith, J. Evans, A. Shrier*, Y. Rajabally, M. Narasimhan, A. ORourke, F. Cowan, and C. Fratter
10 Abstracts
Conclusion: Our data suggests that -511T allele may be a susceptibility factor to MTLE-HS, independently of FS antecedents. The exacerbated inflammatory reaction associated with this allele could lead to cell loss and progression of seizures. These observations must be confirmed in a higher cohort. Supported by a BICE Tecnifar Grant 2009 visuomotor and executive functions. Patients were examined clinically and myoclonus severity was evaluated with myoclonus with action -part from the Unified Myoclonus Rating Scale. On the basis of myoclonus with action score the patients were classified into three disability groups: mild, moderate and severe. 46 healthy volunteers (19 M, 27 F), mean age 32 years, were the controls for the neuropsychological evaluation. Result: The patients with ULD had lower Verbal and Performance IQs than the controls (p<0.001) and impaired performance in flexible visuomotor task (p<0.001). The patients had poorer immediate verbal memory (p<0.01) but delayed memory (percentage of retained material) did not differ between the groups. Patients with mild and moderate disability had impaired executive functions (p<0.01). Most patients with severe disability could not accomplish executive function tests and this group was excluded from this analysis. Conclusion: The ULD patients are impaired in several cognitive domains, in visuomotor, executive and intellectual functions. Delayed memory is normal and memory disorder is not characteristic to ULD. The study has been funded by the Academy of Finland, the NEURO Research Programme and UCB Pharma.
Neuropsychology Tuesday, 02 October 2012

029 NEUROPSYCHOLOGICAL FUNCTIONING IN PAEDIATRIC EPILEPSY SYNDROMES A. F. Lopes*, M. R. Simes*, M. J. Fonseca, J. P. Monteiro, and C. Robalo *University of Coimbra, Coimbra, Portugal; Hospital Garcia de Orta, Almada, Portugal; and Hospital Peditrico de Coimbra, Coimbra, Portugal
Purpose: The aim of the current investigation is to examine neuropsychological functioning in common childhood epilepsy syndromes [Frontal Lobe Epilepsy (FLE), Absence Epilepsy (AE), Benign Epilepsy with Centro-Temporal Spikes (BECTS)], compare them with matched controls and study the influence of epilepsy-related variables. Method: Neuropsychological status was examined in 90 children with epilepsy (30 FLE, 30 AE, 30 BECTS), aged 615 years and compared with a control group. Children with epilepsy were selected based on the following inclusionary criteria: (1) FSIQ 70 (WISC-III), (2) EEG that confirmed the diagnosis of epilepsy and (3) were receiving no more than two antiepileptic medications. Participants completed the following tasks: Memory (List Learning, Rey Complex Figure, Corsi), Language (Rapid Naming, Phonological Awareness, Comprehension, Verbal Fluency), Attention and Executive Functions (Cancellation Task, Trail Making Test (Parts A and B), Tower of London). Result: All epilepsy syndromes showed deficits in language, attention and executive functions. Children with FLE also scored lower in verbal and visual memory. Earlier age at onset was associated with problems in long-term visual memory, sustained attention and executive functions. Children with a longer duration of epilepsy were more likely to present deficits in sustained attention. Seizure frequency and side of focus did not influence results. Conclusion: This study demonstrates cognitive dysfunction in three common childhood epilepsy syndromes, especially in FLE. Also, our results suggest that age at onset and duration of epilepsy are associated with neuropsychological functions outcome. The neurocognitive screening will be an effective tool in assessing those children in risk of school difficulties.
031 EVIDENCE FOR COGNITIVE DEFICITS IN UNTREATED PATIENTS WITH NEWLY DIAGNOSED EPILEPSY J. Witt, and C. Helmstaedter University Clinic of Bonn, Bonn, Germany
Purpose: The objective of our study was to assess cognition in newly diagnosed and untreated patients with epilepsy in order to determine the prevalence and the determinants of cognitive deficits at this early stage of the disease. Method: A total of 247 untreated patients with newly diagnosed epilepsy underwent a brief test battery focusing on attention and executive functions (EpiTrack) and memory (short form of the VLMT). In addition, the assessment included ratings of self-perceived deficits in attention and memory. Result: Impairments in attention and executive functions were seen in 49.4% of the patients, memory deficits in 47.8%. Unimpaired performance in both domains was observed in 27.9% of the cases. Self-perceived deficits in attention were only reported by 28.7% of the patients and memory impairments were complained by 25.1% of the patients. A lower education and a symptomatic, i.e. lesional cause of epilepsy were associated with worse performance in attention and executive functions, whereas worse memory performance was related to generalized tonicclonic seizures. Conclusion: Results indicate a high prevalence of cognitive deficits at an early stage of epilepsy which calls for consideration in the daily clinical care. Patients appear to underreport cognitive deficits. Thus, a routine application of a brief standardized neuropsychological screening before the initiation of a pharmacological treatment would be appreciated to provide a baseline to evaluate subsequent treatment success, to eventually initiate countermeasures, and to monitor the course of the disease.
030 NEUROPSYCHOLOGICAL FUNCTION OF PATIENTS WITH UNVERRICHT-LUNDBORG DISEASE J. Hyppnen*, M. iki*, A. E. Lehesjoki, and R. Klviinen* *Kuopio University Hospital, Kuopio, Finland; and University of Helsinki, Helsinki, Finland
Purpose: Unverricht-Lundborg disease (ULD), an autosomal recessively inherited neurodegenerative disorder characterized by action-activated and stimulus-sensitive myoclonus and epileptic seizures. During years some of the patients become severely incapacitated. The aim of this study was to evaluate cognitive function of patients with ULD. Method: We evaluated cognitive performance of 68 genetically verified ULD patients (37 M, 31 F), mean age 35 years, with a neuropsychological test battery assessing intellectual ability (WAIS-R), verbal memory,
032 COGNITIVE FUNCTION IS IMPAIRED IN PATIENTS WITH IDIOPATHIC GENERALISED EPILEPSY AND THEIR UNAFFECTED FAMILY MEMBERS F. A. Chowdhury*, L. Nashef*, R. D. Elwes*, and M. P. Richardson *King's College Hospital, London, UK; and King's College London, London, UK
Purpose: The profile of neuropsychological impairments in patients with idiopathic generalised epilepsy (IGE) includes a wide range of fron-
11 Abstracts
tal lobe functions. Assessment of neuropsychological function is complex because of the interaction of the underlying aetiological process, consequences of seizures and anti-epileptic medications. Method: Forty age-matched normal control subjects, 36 patients with IGE, and 38 unaffected first-degree relatives of patients were studied using a range of neuropsychological tests; trail-making test, matrix reasoning, verbal fluency (letter and category), N-back working memory task, Stroop response inhibition and Connors Continuous Performance Task (CPT). Verbal IQ was measured using National Adult Reading Test (NART). Statistical testing used Bonferroni correction of 8 for each neuropsychological test administered. Result: Patients performed significantly worse than controls on NART (p=0.006), matrix reasoning (p<0.001), letter and category fluency (p<0.001) and CPT omissions (p<0.001). Relatives also performed significantly worse than controls on matrix reasoning (p=0.002) and CPT omissions (p=0.001), despite having no significant difference in verbal IQ (p=0.711) using NART. There were significant linear trends between the three groups in matrix reasoning (p<0.001), letter and category fluency (p<0.001) and CPT omissions (p<0.001), with relatives falling partway between controls and patients. Conclusion: Reduced cognitive performance is found in unaffected relatives of patients with IGE as well as the patients themselves, suggesting this is related to a familial risk of epilepsy rather than a consequence of seizures or anti-epileptic treatment.
034 RESECTIVE EPILEPSY SURGERY FOR MALFORMATIONS OF CORTICAL DEVELOPMENT IN INFANCY AND EARLY CHILDHOOD T. Otsuki, A. Takahashi, T. Kaido, Y. Kaneko, R. Honda, K. Sugai, E. Nakagawa, and M. Sasaki National Center of Neurology and Psychiatry, Tokyo, Japan
Purpose: Frequent epileptic seizures in infants cause sever epileptic encephalopathy with a catastrophic nature associated with progressive developmental delay. When epileptogenic pathology such as cortical dysplasia is identified, early surgical intervention is considered although risk and prognosis of surgical intervention in infancy and early childhood is not well known. Method: We have operated 56 children with cortical dysplasias less than 6 years old at surgery in our institute during 2000 to Aug 2011. The age at surgery was from 2 to 71 months old (mean 1y11m) and the follow-up period was from 6 months to 10 years (mean 3y10m). All the patients demonstrated disabling daily seizures such as frequent spasms and tonic seizures. Comprehensive presurgical evaluation including EEG, MRI, video-EEG monitoring, PET, MEG and developmental evaluation was indicated to all the children and ictal SPECT with SISCOM analysis was indicated in 27 selected cases. Intracranial EEG monitoring was performed in 7 cases elder than 3 years old under sedation and intensive care. The location of the MRI lesion was frontal in 20, temporal in 5, parietal in 5, occipital in 2, multilobar in 6 and hemispheric in 18 cases (16 hemimegalencephaly). Result: Surgical procedure was 18 hemispherotomy (17 vertical, 1 horizontal), 7 multilobar, 15 lober and 16 focal resection. Seizure outcome was Engel's class I in 39 cases (70%), class II in 2 (3%), class III in 6 (11%) and class IV in 9 (16%). There was no statistical difference in seizure outcome between surgical procedures. Surgical complications were 1 post-operative hydrocephalus, 1 chronic subdural hematoma and 1 transient meningitis. No motality nor sever morbidity was experienced in our series. Conclusion: Favorable surgical prognosis can be obtained by resective epilepsy surgery for children in infancy and early childhood when epileptogenic pathology is demonstrated by MRI and/or functional brain imaging.
Surgical Treatment Tuesday, 02 October 2012

033 SEIZURE OUTCOME TEN YEARS AFTER RESECTIVE EPILEPSY SURGERY - A POPULATION-BASED, PROSPECTIVE, LONGITUDINAL STUDY A. Edelvik*, B. Rydenhag*, R. Flink, and K. Malmgren* *Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; and Uppsala Akademiska Hospital, Uppsala, Sweden
Purpose: The aim of this study was to investigate seizure outcome 10 years after resective epilepsy surgery in a national population-based cohort of adults and children. Method: The Swedish National Epilepsy Surgery Register encompasses data on all epilepsy surgery procedures in Sweden since 1990 and is completely prospective since 1995. Data is collected before and at surgery, and after two, five, 10 and 15 years. In this study, we analysed seizure outcome for all patients who had resective epilepsy surgery in Sweden 19952000 and had undergone 10-year follow-up (N=287). Freedom from seizures with impairment of consciousness (ILAE class 1 and 2) is reported for the year before follow-up. The percentages/numbers of patients with sustained seizure freedom (ILAE class 1 and 2) are also reported. Result: Of the 287 patients, 211 had undergone temporal lobe resections (TLR) and 76 extratemporal resections (XTLR). 10 years after TLR 62% (131/211) were seizure free compared to 59% after two years. 36% (77/ 211) had sustained seizure freedom at 10 years compared to 51% (107/ 211) after two years. 43% (33/76) were seizure free 10 years after XTLR compared to 39% after two years. 26% (20/76) had sustained seizure freedom at 10 years, compared to 37% at two-year follow-up. Conclusion: In this prospective population-based study, the percentage of patients who were seizure free the year before follow-up was stable 10 years after epilepsy surgery, compared to the two years follow-up. However, the percentage of patients with sustained seizure freedom after surgery declined over time.
035 EXTRATEMPORAL EPILEPSY SURGERY IN ELOQUENT BRAIN REGIONS USING FUNCTIONAL NEURONAVIGATION AND INTRAOPERATIVE MRI (IOPMRI) K. Roessler, B. Sommer, P. Grummich, B. Kasper, I. Blmcke, H. M. Hamer, and M. Buchfelder University Hospital Erlangen, Erlangen, Germany
Purpose: A retrospective study was performed to analyze the impact of functional neuronavigation and intraoperative magnetic resonance imaging (iopMRI) during extratemporal epilepsy surgery on neurological and epilepsy outcome. Method: From 20032011 twenty-five patients with a mean age of 36 years (range: 1267; 14 female, 11 male) were resected on focal epileptogenic lesions close to speech/motor areas or adjacent to eloquent fibre tracts. Preoperatively, motor-sensory and speech areas and fibre tracts were mapped using functional MRI and DTI imaging, respectively. Functional data were integrated into intraoperative neuronavigation and displayed through the microscope during surgery. Histopathology was FCD in 5, gliosis in 6, dysembryoblastic neuroepithelial tumor in 2, cavernous hemangioma in 5, ganglioglioma WHOI in 4 and glioma WHOIIII in 3 patients. The postoperative follow-up period was 37.2 (489) months mean.
12 Abstracts
Result: According to iopMRI scans, 100% resection of epileptogenic lesions was achieved in all patients. In 4 of them, an intraoperative second look procedure according to iopMRI was necessary to complete resection. Transient dysphasia was seen in 2/14 patients, permanent dysphasia found in 2/14 patients. Permanent quadrantanopia was observed in 2/8 patients. Of patients with functional mapping of the motor cortex and pyramidal tract, 1/19 experienced a temporary monoparesis. Favourable seizure control (Engel classification I and II) was achieved in 80% of the patients. Conclusion: In our retrospective analysis, we demonstrated that resection of epiletogenic lesions close to eloquent cortex and fibre tracts can be performed safely and efficiently by integration of multimodal neuronavigation and functional imaging during surgery.
A. Reznikov*, H. Valsamis, R. Cracco*, S. Malhotra*, A. Omurtag, A. Fenton*, and S. Zehtabchi *SUNY Downstate Medical Center, Brooklyn, NY, USA; Kings County Hospital Center, Brooklyn, NY, USA; and Bio-Signal Group, Brooklyn, NY, USA
Purpose: To identify the prevalence of EEG abnormalities in patients with altered mental status (AMS) presenting to the emergency department (ED). Up to 10% of patients evaluated in the ED present with AMS. The prevalence of EEG abnormalities in this population is not known. Method: Prospective study at two urban EDs in Brooklyn, NY. Inclusion: patients over 13 years old with AMS. Exclusion: an easily correctable cause of AMS (e.g. hypoglycemia, opioid overdose). A 30-minute EEG was performed on each subject as soon as possible after presentation, usually within 1 hour. Result: 301 patients were screened and 261 enrolled over 10 months. Mean age was 58.9y (SD 19.9). 78% of EEGs were abnormal. EEG findings: slowing only - 142 (54.4%), normal - 51 (19.5%), interictal epileptiform discharges + slowing - 32 (12.3%), triphasic waves - 9 (3.4%), burst-suppression - 8 (3.1%, iatrogenic in 7), status epilepticus (SE) - 7 (2.7%), seizure - 4 (1.5%), epileptiform only - 3 (1.1%), uninterpretable 5 (1.9%). 41 (15.7%) studies were partially obscured but contained sufficient interpretable data for clinical categorization. Conclusion: ED patients with AMS have a very high prevalence of EEG abnormalities, most often diffuse slowing. 4.2% revealed SE or isolated seizure(s), but another 2.7% demonstrated burst-suppression due to acute treatment of SE. Nearly 20% of EEGs were normal, which rules out SE, seizure and encephalopathy as causes of AMS. Fewer than 2% were completely obscured by artifact. EEG in the ED can provide useful information to narrow the differential diagnosis of AMS patients. Supported by 1RC3NS070658
036 USEFULNESS OF POSITRON EMISSION TOMOGRAPHY IN DECISION MAKING FOR EPILEPSY SURGERY C. Rathore*, J. Dickson, P. Ell, and J. Duncan *Sree Chitra Institute of Medical Sciences and Technology, Trivandrum, India; University College London Hospitals, London, UK; and National Hospital for Neurology and Neurosurgery, London, UK
Purpose: To investigate the utility of Flurodeoxy-glucose Positron Emission Tomography (FDG-PET) in decision making for epilepsy surgery Method: All patients with nonlocalizing or discordant information on non-invasive evaluation (clinical, electrophysiological and 3T-MRI) underwent FDG-PET at our centre. PET scans were reviewed by two investigators blinded to clinical data. PET was considered useful if it led to surgery directly, helped in planning intracranial EEG (icEEG) or made surgery improbable. Final localization was based upon the discussion in multidisciplinary meetings supported by icEEG and/or postoperative seizure freedom, when available. Result: Ninety adult patients (median age, 34years) underwent FDGPET; 76 had normal MRI and 14 had electrophysiological and MRI discordance. Final localization was mesial temporal lobe epilepsy (MTLE, n=6), lateral TLE (n=22), frontal lobe epilepsy (n=32), and temporal-plus epilepsy or other extratemporal lobe epilepsies (15 each). FDG-PET scan was normal in 46 patients. It led to surgery without intracranial EEG in four patients (right MTLE) and helped in planning icEEG in 31 patients. Seven patients had bilateral/diffuse hypometabolism making surgery improbable and FDG-PET gave false localizing information in two patients. Nine Of 14 patients who underwent surgery to date became seizure free and three patients could not proceed to surgery after icEEG. Others are awaiting icEEG (16) or declined surgery. Only three patients with normal PET scan proceeded to icEEG or surgery (p=0.001). FDG PET provided equivalent information in all epilepsy localizations. Conclusion: In ~45% of presurgical patients with normal or discordant MRI, PET scan provided information that helped decision making.
038 IS ECOG DURING EPILEPSY SURGERY FOR MESIAL TEMPORAL SCLEROSIS OF ANY USE? J. Chan, N. Lawn, and J. Dunne Royal Perth Hospital, Perth, WA, Australia
Purpose: The use of electrocorticography (ECoG) in epilepsy surgery varies widely as do methods of anaesthesia, recording and interpretation. Its role in guiding epilepsy surgery is debated particularly in patients with mesial temporal sclerosis (MTS). Significant inter-centre disparities in outcome are seen following MTS surgery, with some centres using ECoG reporting better outcomes. We sought to study the ECoG findings and seizure outcomes in patients undergoing epilepsy surgery for MTS. Method: We studied 73 consecutive patients with refractory epilepsy who had surgery for MTS with a minimum of 1-year follow up (median 8.9 years, range 118.8 years). All surgeries were performed under general anaesthetic, usually sevoflurane. Pre-resection ECoG was recorded with two 4-contact subdural strips (inferior temporal and lateral temporal). Antero-mesial temporal resection was performed and tailored based on the initial and postresection ECoG. ECoG was analysed blinded to patient details and outcomes. Result: Overall, 58 patients (79%) had an Engel class I outcome. Of 61 patients (84%) with pre-resection spikes, those with an inferomesial rather than lateral maximal field had a better outcome (88% mesial vs. 64% lateral Engel class I; p=0.04). Engel class I outcomes occurred in 75% of 12 patients with no pre-resection spikes, 94% of 34 patients with pre-resection spikes and none after initial/additional resection, and 63% of 27 patients with residual spikes after initial/additional resection (p=0.01). Conclusion: ECoG during surgery for MTS at our centre provides useful information for guiding surgery and predicting prognosis.
Clinical Neurophysiology Tuesday, 02 October 2012

037 EEG FINDINGS IN 261 SEQUENTIAL PATIENTS WITH ALTERED MENTAL STATUS PRESENTING TO THE EMERGENCY DEPARTMENT A. C. Grant*, S. Abdul-Baki*, V. Arnedo*, G. Chari*, E. Koziorynska*, D. Maus*, T. Mcsween*, K. A. Mortati*,
13 Abstracts
039 IMPLEMENTATION OF HOME VIDEO-EEG-TELEMETRY AT KING'S COLLEGE HOSPITAL (KCH), LONDON F. Brunnhuber*, S. Goyal, D. Amin, Y. Nguyen, and M. P. Richardson *King's College Hospital, London, UK; London; and King's College London, London, UK
Purpose: Aim: We present KCH's experience of the first 50 home videotelemetry (HVT) patients. Method: HVT met the MRC definition of a complex intervention, and we used its guidance to evaluate the process of piloting, evaluating, developing and implementing this new clinical service. Result: Our feasibility study (n=5) with a test re-test design found no difference in the quality of recording or clinical yield between inpatient video-telemetry (IVT) and HVT. The pre-implementation study (n=8) showed an excellent patient satisfaction. We also discuss the findings of the main stakeholder survey (consultants and technicians). Our economic modelling demonstrates a clear financial superiority of HVT over IVT. Conclusion: Our findings show that diagnostic video-telemetry for seizure classification and poly-somnographies can be carried out safely at the patients home and poses no security risks for staff and can be effectively integrated into the service offering of a tertiary care centre as a routine home or community-based procedure. Community or home-based MDTs (multidisciplinary team meetings) is an unexpected advantage of HVT and has the potential for future development for patients with complex conditions. HVT was preferred by our patients over IVT and provides a means of reaching out to some of the most vulnerable patient groups (children, patients with learning difficulties or other mental health problems), who would not otherwise benefit from this investigation or only under great difficulties. We hope to encourage other clinical neurophysiology departments and epilepsy centres to take advantage of our experience and consider adopting and implementing HVT, with the aim of a nationwide coverage. depth recordings with up to 122 channels. The datasets provide EEG data for an average recording time of 150 hours at sampling rates of 2502500 Hz. EEG recordings have undergone standardized annotation with details on the timing, patterns and evolution of seizures. Data files are supplemented by comprehensive clinical patient information, MR imaging data and antiepileptic medication. Conclusion: The EU project has resulted in the by far largest and most comprehensive database for human surface and intracranial EEG recordings. Information on access to data from this database for research groups can be obtained at www.epilepsy-database.eu.
Functional MRI Wednesday, 03 October 2012

041 IMAGING MEMORY IN TEMPORAL LOBE EPILEPSY: REORGANISATION OF MEMORY FUNCTION FOLLOWING ANTERIOR TEMPORAL LOBE RESECTION RESULTS OF A LONGITUDINAL FMRI STUDY S. Bonelli*, P. J. Thompson, M. Yogarajah, R. Powell, R. Samson, A. W. Mcevoy, M. Symms, M. Koepp, and J. Duncan *Medical University of Vienna, Vienna, Austria; Institute of Neurology, London, UK; and National Hospital for Neurology & Neurosurgery, London, UK
Purpose: Anterior temporal lobe resection (ATLR) may impair memory function, typically verbal memory following left and visual memory following right ATLR. We investigated reorganisation of memory function in patients with temporal lobe epilepsy (TLE) before and after left or right ATLR and the efficiency of postoperative memory networks. Method: We studied 46 patients with unilateral medial TLE (26 left) on a 3T GE-MRI scanner. All subjects had neuropsychological testing and performed an fMRI memory encoding paradigm for words, pictures and faces preoperatively and again four months after ATLR. Result: Event-related analysis revealed that left TLE patients had greater left activation in the posterior medial temporal lobe (MTL) for encoding words postoperatively than preoperatively. Relatively greater pre- than postoperative activation for encoding words in the ipsilateral posterior MTL correlated with better verbal memory outcome after left ATLR. Four months after left ATLR greater postoperative than preoperative activation in the ipsilateral posterior MTL correlated with less good postoperative verbal memory performance. These postoperative effects were not observed for visual memory after right ATLR. Conclusion: We found effective preoperative reorganisation of verbal memory function to the ipsilateral posterior MTL, suggesting that it is the capacity of the posterior remnant of the ipsilateral hippocampus rather than the functional reserve of the contralateral hippocampus that is important for maintaining verbal memory function after ATLR; early postoperative reorganisation to ipsilateral posterior or contralateral MTL structures is inefficient. We also conclude that visual memory function in right TLE is affected differently by right ATLR than verbal memory in left TLE.
040 THE EUROPEAN EEG DATABASE AS A NEW STANDARD FOR LONG-TERM EEG RECORDINGS IN EPILEPSY PATIENTS A. Schulze-Bonhage*, M. Levanquyen, F. Sales, M. Neufang*, A. Dourado, and M. Ihle* *University Hospital Freiburg, Freiburg, Germany; Hpital de la Piti-Salptrire, Paris, France; Hospitais de Universidade de Coimbra, Coimbra, Portugal; and Universidade de Coimbra, Coimbra, Portugal
Purpose: Access to high quality long-term EEG recordings of epilepsy patients has so far been limited for many research groups active in the field of clinical neurophysiology and epileptology. We here report on a newly established European Database offering high-quality surface and intracranial EEG data for EEG and epilepsy research. Method: Supported by the EU-project EPILEPSIAE (Evolving Platform for Improving Living Expectation of Patients Suffering from IctAl Events, Grant 211713), the epilepsy centers at the University Hospitals Freiburg, Germany, Hopital Piti-Salptrire in Paris, France, and the University Hospital Coimbra, Portugal have designed a database containing long-term intracranial and surface EEG recordings. Inclusion criterie were long-term recordings with a minimum of 4 days duration containing 5 clinically manifest seizures. Result: The complete European EEG database comprises 275 long-term recordings from epilepsy patients, 223 obtained by surface-EEG using the 1020 recording system and 52 based on intracranial subdural or
042 LOCALIZATION OF THE ICTAL ONSET ZONE USING INTERICTAL EEG-FMRI IN THE PRESURGICAL EVALUATION OF CONSECUTIVE PATIENTS WITH REFRACTORY FOCAL EPILEPSY S. Tousseyn, P. Dupont, S. Sunaert, and W. Van Paesschen KU Leuven, University Hospitals Leuven, Leuven, Belgium
14 Abstracts
Purpose: The aim of this study was to explore how Blood Oxygen Level Dependent (BOLD) responses to interictal epileptic spikes during EEGcorrelated functional MRI (EEG-fMRI) relate to the ictal onset zone (IOZ). Method: Twenty-one consecutive adults with refractory focal epilepsy and a well delineated IOZ after a full presurgical evaluation including subtraction ictal SPECT co-registered to MRI (SISCOM) were studied. We delineated the IOZ as the region of SISCOM hyperperfusion (Z>1.5) within the planned or effective resection zone. Positive and negative fMRI responses (p<0.001) to clinically concordant and visually marked spikes (after standard EEG artifact removal) were used for qualitative assessment of overlap with the IOZ. Result: We observed clinically concordant interictal spikes in 10 of 21 patients during fMRI, which resulted in both activations and deactivations in all 10 patients. The maximal activation was statistically more significant than the maximal deactivation in 8/10. The maximal significant activation cluster overlapped the IOZ in 9/10, although the voxel of maximal activation was found within the IOZ in only 3/9. The cluster of maximal deactivation was concordant with the IOZ in 2/10, with the voxel of maximal deactivation inside the IOZ in 1/2. Conclusion: EEG-fMRI in consecutive patients with refractory focal epilepsy undergoing presurgical evaluation recorded epileptic spikes in only 48%. The maximal significant fMRI activation cluster overlapped the ictal onset zone in 90% of patients with spikes during fMRI. However, the voxel of maximal activation was localized inside the IOZ in only one third. This study is funded by a grant for Applied Biomedical Research (TBM) of the Institute of Innovation by Science and Technology Flanders (IWT) (080658). ILAE-class-IV post-surgical outcome. One patient did not proceed to surgery. Conclusion: Simultaneous icEEG-fMRI reveals BOLD changes in distributed networks across the whole brain for very focal epileptic discharges. These data suggest that the test may have clinical utility for predicting surgical outcome.
044 PREOPERATIVE FMRI IN TEMPORAL LOBE EPILEPSY: ASSESSMENT OF LANGUAGE-RELATED AREAS F. Villani*, C. Rosazza*, F. Ghielmetti*, L. Minati*, F. Deleo*, A. R. Giovagnoli, G. Didato*, P. Vitali, A. Parente, L. DIncerti*, R. Spreafico, and M. Bruzzone* *IRCCS Foundation Besta Neurological Institute, Milan, Italy; Fondazione IRCCS Istituto Neurologico C. Besta, Milano, Italy; Istituto Neurologico Mondino, Pavia, Italy; and I.R.C.C.S. Foundation Neurological Institute, Milano, Italy
Purpose: Surgical removal of part of the temporal lobe (TL) for temporal lobe epilepsy (TLE) may be complicated by language impairments. Functional MRI (fMRI) may predict postsurgical language outcome. In our study we assessed the impact of TLE on the language network. Method: Data collected from 67 TLE patients (40 LTLE, 27 RTLE) were retrospectively analyzed with 15 controls. The fMRI assessment included response naming (RN), verb generation (VGEN) and fluency (FT) tasks. A whole-brain and a ROI-based analysis with lateralization indices were performed. Language tests were administered. Result: The overall activation was left-lateralized in patients and controls. The FT elicited weaker activation of the TL compared to the other tasks. TL was activated anteriorly by the RN task, posteriorly by the VGEN task. LTLE patients showed a decreased left-lateralization compared to controls. In RTLE patients the RN and FT revealed a left-lateralization similar to controls, but VGEN produced posterior temporal activations also on the right side with a less lateralized language activation pattern. The language assessment showed that left and right TLE patients had significantly lower scores than controls on the Boston naming test. Conclusion: RN and VGEN were the most useful tasks to lateralize and localize language areas in the TL. LTLE patients showed reorganization of language in the right TL, suggesting an adaptive recruitment of contralateral regions. The paradoxical recruitment of right posterior temporal areas in RTLE patients may be related to language processing, as also right temporal regions are involved in accessing lexical and semantic information.
043 MAPPING THE IRRITATIVE ZONE USING SIMULTANEOUS INTRACRANIAL EEG-FMRI AND COMPARISON WITH POSTSURGICAL OUTCOME U. J. Chaudhary*, D. W. Carmichael, R. Rodionov*, S. Vulliemoz, C. Scott, A. W. Mcevoy, C. Micallef, B. Diehl, M. C. Walker*, J. Duncan*, and L. Lemieux* *UCL Institute of Neurology, London, UK; UCL Institute of Child Health, London, UK; University Hospital of Geneva, Geneva, Switzerland; and National Hospital for Neurology and Neurosurgery, London, UK
Purpose: To determine the clinical significance and distribution of spike-related haemodynamic changes across the whole brain using simultaneous intracranial electroencephalography and functional magnetic resonance imaging (icEEG-fMRI), particularly as icEEG has limited spatial coverage. Method: Five patients with frontal lobe epilepsy undergoing invasive presurgical evaluation were scanned. One to two 10-minutes EPI-sessions (TE/TR 40/3000ms; slices/gap: 38x2.5mm/0.5mm) and T1 volume were acquired on 1.5T scanner using head RF-coil with patient at rest. 64 channels of icEEG were recorded during EPI and reviewed after removing scanner-related-artefacts. Pre-processed images were analysed using SPM8. Spikes were classified according to their morphology and spatiotemporal distribution on icEEG and represented as zero-duration events (different types were modelled in separate regressors) and convolved with the canonical HRF and derivatives. SPM[F] maps obtained for each spike type and for all types combined were overlaid on co-registered T1volume and compared with the irritative zone defined on icEEG. Result: All patients had statistically significant spike-related hemodynamic changes. BOLD changes were seen within the irritative zone in three patients; remote clusters were seen in all patients. BOLD clusters were predominantly in the hemisphere containing the irritative zone in three patients with ILAE class-I outcome post-surgically, and were distributed bilaterally remote from the irritative zone in one patient with
Structural and Functional Imaging Wednesday, 03 October 2012

045 DECREASED FUNCTIONAL FRONTAL LOBE CONNECTIVITY IS ASSOCIATED WITH COGNITIVE IMPAIRMENT IN PEDIATRIC FRONTAL LOBE EPILEPSY H. Braakman*, M. Vaessen*, J. Jansen*, M. Debeij-Van Hall, P. Hofman*, J. Vles*, A. ldenkamp*, and W. Backes* *Maastricht University Medical Center, Maastricht, The Netherlands; and Epilepsy Center Kempenhaeghe, Heeze, The Netherlands
15 Abstracts
Purpose: Cognitive impairment is frequent in frontal lobe epilepsy (FLE), but its etiology is unknown. With functional MRI, we explore the relationship between brain activation, functional connectivity and cognitive functioning in a cohort of pediatric FLE patients and healthy controls. Method: Thirty-four children aged 8 to 13 years with FLE of unknown cause and 41 healthy age-matched controls underwent neuropsychological assessment and structural and functional brain MRI. We investigated to which extent brain regions activated in response to a working memory task and assessed functional connectivity between distant brain regions. Data of patients were compared to controls and patients were grouped as cognitively impaired or unimpaired. Result: Children with FLE showed a global decrease in functional brain connectivity compared to healthy controls, while brain activation patterns remained relatively intact. Children with FLE complicated by cognitive impairment typically showed a decrease in frontal lobe connectivity. This decreased frontal lobe connectivity comprised both connections within the frontal lobe, as well as connections from the frontal lobe to the parietal lobe, temporal lobe, cerebellum, and basal ganglia. Conclusion: Decreased functional frontal lobe connectivity is associated with cognitive impairment in pediatric FLE. The importance of functional integrity within the frontal lobe network, as well as its connections to distant areas provides new insights in the etiology of the broadrange cognitive impairments in children with FLE. Purpose: To map hippocampal subfield degeneration in patients with mesial temporal lobe epilepsy (mTLE) and hippocampal sclerosis (HS) using conventional MRI. Method: We studied 82 patients with unilateral mTLE and HS (51 left, 31 right) in context of pre-surgical evaluation and 81 healthy controls. MRIs were acquired using standard MPRAGE sequences at 3 Tesla. Volumes of hippocampal regions CA1, CA2-3, CA4 and dentate gyrus, subiculum, presubiculum, fimbria, and hippocampal fissure were estimated using a recently developed method designed for automated analysis on conventional MRI (Van Leemput et al., 2009, Hippocampus 19:549). Result: Atrophy of all hippocampal subregions ipsilateral to HS other than the hippocampal fissure was observed (p=0.001). Global hippocampal volume was asymmetrically bilaterally atrophic in patients, as was fimbria volume in patients with left mTLE (p=0.01). The only clinicalanatomical correlation that existed was between duration of mTLE and volume of the ipsilateral fimbria (p=0.02). However, this effect did not survive the necessary correction for age, given that age and ipsilateral fimbria were also significantly related (p=0.03). Conclusion: These results are consistent with histological work indicating that diffuse/total HS is common in patients with mTLE, and that preservation of CA2 is seen in only a relatively small proportion of patients (Blumcke et al., 2007, Acta Neuropathol 113:235). The automated method of hippocampal subfield quantification used here is adaptable to pathological hippocampal structure, as illustrated in our patients with unilateral HS, and is therefore recommended for large-scale studies in neurological contexts.
046 STRUCTURAL CHANGES OF THE WHITE MATTER IN PATIENTS WITH JUVENILE MYOCLONIC EPILEPSY C. Roth, M. Belke, K. Menzler, S. Krach, F. Paulus, A. Jansen, M. Blanke, W. Einhuser-Treyer, F. Bremmer, F. Rosenow, and S. Knake Philipps University Marburg, Marburg, Germany
Purpose: Juvenile myoclonic epilepsy (JME) is a common type of generalized epilepsy. Amongst others it is characterized by the absence of structural brain abnormalities using magnetic resonance imaging (MRI) in the clinical routine. Recent findings in MRI studies however suggest regional changes of the brain in patients with JME, albeit those findings are partly inconsistent. There has been a spatial variability in the pathological findings even though a tendency towards changes in the frontal cortex can be remarked. Method: 19 patients with JME and 19 healthy controls, matched by sex, age and education were had a 3 Tesla MRI scan including a diffusion MRI scan (DTI). Those DTI images were analysed using Tract-Based Spatial Statistics (TBSS) and the fractional anisotropy (FA) as a measure of the integrity of the white matter was computed. Result: We found a significant reduction in the FA within the corpus callosum (CC) in patients with JME compared to healthy controls. The changes were mainly in the anterior region of the corpus callosum. Conclusion: The recuced FA within the corpus callosum suggests an impaired structural connectivity concerning the frontal lobe. Similar findings have been published by a british group last year, so this may be considered as a robust result. Our findings are further evidence that regional changes of the brain might exist in generalized epilepsy as well and support the hypothesis of impaired frontal network in patients with JME.
048 ALTERED INTERACTIONS WITHIN NEURAL NETWORK SUPPORTING VERBAL WORKING MEMORY DUE TO HIPPOCAMPAL SCLEROSIS P. Campo*, M. I. Garrido, R. J. Moran, I. Garca-Morales, A. Gil-Nagel, R. J. Dolan, and K. J. Friston *Universidad Autonoma de Madrid, Madrid, Spain; Wellcome Trust Centre for Neuroimaging, London, UK; University Hospital of San Carlos, Madrid, Spain; and Hospital Ruber International, Madrid, Spain
Purpose: To evaluate local and remote changes in effective connectivity among the regions of the neural network underlying encoding processes in patients with mesial temporal lobe epilepsy (mTLE) associated with unilateral hippocampal sclerosis (HS). Method: We compared dynamic causal models, extracted from magnetoencephalographic recordings during verbal WM encoding, in mTLE patients (n = 20) and controls (n = 12). Result: Bayesian model comparison indicated that the best model included bilateral, forward and backward connections, linking inferior temporal cortex (ITC), inferior frontal regions (IFC) and medial temporal lobe (MTL). Differences in model coefficients revealed that patients were characterized by a decreased ipsilesional MTL-ITC connectivity, and an increased bidirectional IFG-MTL connectivity in the contralesional hemisphere (all p < 0.05). The influence from right IFC to right MTL was inversely related to task performance (R2 = -.62, p < 0.05). A negative correlation was also found between the connectivity strength of ipsilesional MTL-ITC and that of the contralesional MTL-IFG interaction (R2 = -.44, p = 0.05). Conclusion: Left HS led to a dynamic adjustment/reorganization of the remaining network supporting verbal WM, affecting connections considered to be of great functional relevance for WM performance. This altered connectivity pattern may reflect compensatory, with varying degrees of efficacy, and pathophysiological mechanisms underlying verbal encoding deficits in left mTLE patients. Current results confirm those of a previous study and reinforce the hypothesis that a distributed neural network is affected as a result of localized brain damage.
047 HIPPOCAMPAL SUBFIELD ANALYSIS IN MESIAL TEMPORAL LOBE EPILEPSY M. Deppe*, B. Weber, J. Schoene-Bake, and S. S. Keller *University of Muenster, Muenster, Germany; University of Bonn, Bonn, Germany; and King's College London, London, UK
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Acknowledgments: PC was supported by Spanish Ministry of Science and Innovation (Grant # RYC-2010-05748).
Paediatric Epilepsy Wednesday, 03 October 2012

049 PAROXYSMAL NON-EPILEPTIC EVENTS IN INFANTS AND TODDLERS: A SEMIOLOGY STUDY L. Chen*, E. P. Knight, A. Shahid, and I. Tuxhorn *1st Affiliated Hospital of Guangzhou Medical College, Guangzhou, China; and Rainbow Babies and Childrens Hospital, Ohio, USA
Purpose: Paroxysmal non-epileptic events are frequently encountered in pediatric population. We report our experience with PNEEs in a group of infants and toddlers and analysis the clinical characteristic of the events. Method: Retrospectively reviewed all video EEG (VEEG) studies performed from January 2010 to April 2011. We included in the study consecutive patients 2 years old or younger who had PNEEs recorded. Semiological analysis included: type of event, time of occurrence, clear onset and end, etc. Result: Out of 81 patients 31 (38.3%) had non-epileptic events, 12 girls and 19 boys (P>0.05). Three had both epileptic and non-epileptic seizures and 28 had only non-epileptic events. Six had abnormal interictal EEG. Eight had family history of epilepsy (25.8%). Ten were developmental delay, and eleven had neurological abnormalities. Events occurred during wakefulness in 16 (51.6%, P<0.05); during sleep in 7 (22.6%); in both awake and sleep in 7 (22.6%). On semiology, 20 had behavioral features (64.5%), 10 with arrest of activity, 8 with staring, 6 with crying and 5 with vocalization. 23 had motor features (74.2%) and 9 had autonomic features (29.0%). Events classification: 8 staring spell (25.8%), 7 normal infantile behavior (22.6%), 7 sleep myoclonus (22.6%), 4 shuddering attacks (12.9%), 4 infantile masturbation (12.9%), one tic, onechoreoathetosis, one hyperekplexia, one gastro-esophageal reflux and one episode of discomfort. Conclusion: Paroxysmal non-epileptic events are very common in infants and toddlers. Males were more than female in the study group. Non-epileptic staring spell is the most common PNEEs seen in this age group.
Foundation Trust, Preston, UK; ***University of Glasgow and Royal Hospital for Sick Children, Glasgow, Glasgow, UK; Tayside Children's Hospital, Dundee, UK; Leeds General Infirmary, Leeds, UK; and University of Nottingham, Nottingham, UK
Purpose: To assess the quality of paediatric care for UK children, young people and families affected by epilepsies and seizures. Method: In 2009, the Royal College of Paediatrics and Child Health (RCPCH) Epilepsy 12 Audit began a pragmatic audit of UK paediatric epilepsy care against national guidelines. A project board representing UK stakeholders invited participation from all relevant local hospital and community paediatric services. Audit domains were: 1. clinical service description; 2. 12 clinical performance indicators and 3. a specially developed patient-related experience measure (PREM). The service description was completed at the onset. Lists of children referred for electro-encephalography helped identify eligible children aged 1 month to 16 years who had received a first paediatric assessment for afebrile paroxysmal episode(s) within a 6 month period from 2009. Retrospective data from case-notes review of the subsequent 12 months were entered onto a web-based database. Children commenced on anti-epileptic medication were invited by letter to complete an anonymised PREM questionnaire. Result: Data collection was completed in November 2011 and is currently undergoing further analysis. All 197 audit units and 21 regions enrolled. Participation rates were 98% (193/197) for clinical service description, 94% (186/197) for clinical audit and 87% (172/197) for PREM domains. The clinical cohort consisted of 4991 patients, median age 6.3 years, M:F 54:46%. 44% (2175/4991) of first paediatric assessments occurred within an acute presentation. 19% (974/4991) of children had a documented neurodisability. Diagnosis of paroxysmal episode(s) at first assessment was recorded as: 46% (2298/4991) epileptic; 18% (897/ 4991) non-epileptic and 36% (1796/4991) uncertain. Diagnosis after 12 months of care was recorded as: 6% (312/4991) single or single cluster epileptic seizure(s); 36% (1774/4991) 2 or more epileptic seizures; 44% (2198/4991) non-epileptic and 14% (707/4991) uncertain. Conclusion: The paediatric epilepsy community, including acute and community services and patient organisations, has contributed to the largest description of the performance of paediatric epilepsy care in the UK to date. From the preliminary analysis, just over half the children with paroxysmal episode(s) presented non-acutely with one third eventually diagnosed as having recurrent epileptic seizures. Over the 12 months of follow-up, diagnosis varied and diagnostic uncertainty decreased. Final results will be placed in the public domain in September 2012.
050 EPILEPSY12 - UNITED KINGDOM COLLABORATIVE CLINICAL AUDIT OF HEALTH CARE FOR CHILDREN AND YOUNG PEOPLE WITH SUSPECTED EPILEPTIC SEIZURES C. Dunkley*, B. Waldron, R. Maini, F. Williams, A. Brown, R. Ranmal, D. Flower**, F. Colaco, K. Bowyer, L. Notghi, K. Martin, R. Chin, H. Basu, J. Paton***, M. Kirkpatrick, C. Ferrie, and W. P. Whitehouse *Sherwood Forest Hospitals, Sutton in Ashfield, UK; Leicester Children's Hospital, Leicester, UK; University of Dundee, Dundee, UK; Nottingham University Hospitals NHS Trust, Nottingham, UK; Royal College of Paediatrics and Child Health, London, UK; **Bristol Royal Hospital for Children, Bristol, UK; Scottish Children's Research Network, Dundee, UK; Birmingham Children's Hospital, Birmingham, UK; University of Edinburgh and Royal Hospital for Sick Children, Edinburgh, UK; Lancashire Teaching Hospitals NHS
051 YOUNG ADULT ISCHEMIC STROKE-RELATED ACUTE SYMPTOMATIC AND LATE SEIZURES: RISK FACTORS R. Roivainen, E. Haapaniemi, J. Putaala, M. Kaste, and T. Tatlisumak Helsinki University Central Hospital, Helsinki, Finland
Purpose: We assessed risk and baseline factors associated with acute symptomatic seizure (ASS, occurring < 7 days), and late poststroke seizure (LPS, > 7 days) after ischemic stroke in young adults. Method: We included all consecutive patients aged 15 to 49 with firstever ischemic stroke (n=1008) between 1994 and 2007 treated at the Helsinki University Central Hospital, using Cox proportional hazard models to identify factors associated with seizures. Adjustment was for age, gender, vascular risk factors, admission hyperglycemia (> 6.1 mmol/L) and hyponatremia (< 137 mmol/L), use of psychiatric medication, stroke severity (NIH Stroke Scale), and anatomic (Bamford criteria) and etiologic (Trial of Org in Acute Stroke Treatment) stroke subtype. Result: ASSs emerged in 35 (3.5%) patients. LPSs (n=102) occurred at a cumulative rate of 6.1% at 1 year to 11.5% at 10 years. In multivariate
17 Abstracts
analysis, anxiolytic use at time of index stroke (hazard ratio 13.43, 95% confidence interval 3.9146.14), moderate stroke severity (3.95, 1.86 8.41), cortical involvement (3.69, 1.668.18), and hyponatremia (3.26, 1.417.57) were independently associated with ASSs. Risk factors for LPSs were total anterior circulation infarct (15.94 7.6233.33), partial anterior circulation infarct (3.48, 1.527.93), history of ASS (3.94, 2.07 7.48), antidepressant use at the time of LPS (3.88, 2.466.11), hemorrhagic infarct (1.94, 1.193.15), male gender (1.79, 1.102.92), and hyperglycemia (1.62, 1.052.51). Conclusion: Despite the more heterogeneous etiologic background of ischemic stroke in young adults, major risk factors are similar to older patients. Risk factors for ASS and LPS differ and include factors that are not directly related to stroke characteristics. regional neurosciences centre. Patients in whom VGKC antibodies were identified were given immunotherapy in addition to their antiepileptic drug (AED) therapy. Clinical characteristics and response to immunotherapy were analysed. Result: Out of 128 patients tested, 4 had high titres of VGKC antibodies (>400 pM). Three are male, age range was 36 to 77 years. Seizure semiology was suggestive of temporal lobe onset in all patients. All patients had on going seizures in spite of treatment with AED. One patient had CASPR2 antibodies, the other 3 were negative for both LGI1 and CASP2 antibodies. One patient had thymic enlargement. All patients were given immunotherapy with steroids and azathioprine, resulting in fall in VGKC titres. In the patient with thymic enlargement VGKC titres fell following thymectomy. All patients experienced improvement in seizure control with immunotherapy, and 3 have remained seizure free. Conclusion: Identifying patients with VGKC antibodies associated with epilepsy has significant therapeutic implications, as immunotherapy appears to result in complete control of previously AED resistant seizures. The pathogenic antibody in patients presenting with epilepsy maybe directed towards an as yet unidentified component of the VGKC receptor complex.
052 KETOGENIC DIET AS AN EFFECTIVE ALTERNATIVE THERAPY IN CHILDHOOD REFRACTORY EPILEPSY: A SYSTEMATIC REVIEW A. K. Somale, and S. V. Kondekar Topiwala National Medical College, Mumbai, India
Purpose: To systematically review recent studies on efficacy and safety of ketogenic diet in pediatric refractory epilepsy. Method: Literature reviewed using Medline searches and Cochrane Library with the keywords epilepsy/therapy, refractory epilepsy, and the text word ketogenic diet. Bibliographies of papers located by searches and review articles were compiled. Papers published after year 2000, from various subcontinents worldwide, reporting use of ketogenic diet in children <18 years of age with medically refractory epilepsy of varied etiology like mitochondrial disorders, cortical dysplasia and symptomatic epilepsy were selected. The outcome measures used were the percentage of patients with complete elimination of seizures and >50% reduction in seizures, deaths and diet related adverse events. Result: Nineteen studies met all criteria for inclusion. It included 6 retrospective, 6 prospective, 2 multicentric trials, 3 systematic reviews and 2 randomized controlled trials. The estimated proportion for obtaining complete seizure control by combined analysis (confidence profile method) was 29.31% (95% confidence interval [CI]: 0.26310.3250) and was 41.81% (95% CI: 0.3838 0.4531) for greater than 50% reduction in seizures. Common adverse events observed were gastrointestinal disturbances, infrequent lipid abnormalities and renal stones, however few deaths 1.29%(CI: 0.66 2.21) were reported while on the diet. Conclusion: There is strong upcoming evidence in last decade to support the safe and effective use of ketogenic diet in children with refractory epilepsy.
054 EPILEPSY AND OTHER NEUROLOGICAL MANIFESTATIONS ASSOCIATED WITH TUBEROUS SCLEROSIS COMPLEX P. Major*, F. Mathieu, L. Ct*, L. Crevier*, A. S. Kristof, and J. Landry *CHU Sainte-Justine - Universit de Montral, Montral, Canada; University of Toronto, Toronto, Canada; and McGill University, Montral, Canada
Purpose: Tuberous sclerosis complex (TSC) is a frequent cause of structural focal epilepsy. This study aims to describe the characteristics of epilepsy and associated neurological manifestations in a large population of patients with TSC. Method: Retrospective analysis of all patients who were admitted to the hospital or evaluated in the emergency room at the CHU Sainte-Justine (Montral) with a diagnosis of definite TSC from January 1987 to July 2011. Result: In 98 patients with a definite diagnosis of TSC, 79 (80%) had epilepsy. The average age at seizure onset was 0.8 years (range = 0 to 8 y; SD = 1.6 y). Intractable epilepsy was found in 28/79 (35%), including 2 patients who became seizure free after surgery. Average age at last follow-up visit was 18 years (range = 0 to 43 y; SD 10). Developmental delay was diagnosed in 56 (57%) patients, including 47 (83%) with epilepsy and 22/56 (40%) with intractable epilepsy. Of 12 (12%) patients with autistic spectrum disorder (ASD), 11 (92%), and 5/12 (42%) had intractable epilepsy. By mutational analysis (25/98 patients), epilepsy was reported in 16/18 (89%) patients with mutations in TSC2, and in 2/4 (50%) patients with mutations in TSC1. Of the patients with subependymal giant cell astrocytoma (SEGA) (10/98), 5 underwent surgery, and 3 were treated with mTOR inhibitors. Conclusion: In patients with TSC attending a tertiary center, epilepsy, developmental delay, and ASD were common. Epilepsy was usually first observed in the first year of life, and was intractable in one third of patients.
Symptomatic Epilepsy Wednesday, 03 October 2012

053 VGKC ANTIBODIES IN EPILEPSY: DIAGNOSTIC YIELD AND THERAPEUTIC IMPLICATIONS J. Lilleker Greater Manchester Neurosciences Centre, Salford, UK
Purpose: Voltage gated potassium channel (VGKC) antibodies are directed against trans-synaptic and neuronal cell adhesion molecules. Recent studies have identified the presence of these antibodies in various cohorts of patients with epilepsy, and have suggested a potential aetiological role for VGKC antibodies in epilepsy. Method: We have undertaken systematic testing for VGKC antibodies in patients with otherwise unexplained adult onset epilepsy, seen at a
055 TRAUMATIC BRAIN INJURY AND SUBSEQUENT RISK OF UNPROVOKED SEIZURES: A POPULATION-BASED CASE-CONTROL STUDY B. Mahler, C. Adelw, T. Andersson, A. Ahlbom, and T. Tomson Karolinska Institutet, Stockholm, Sweden
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Purpose: To study traumatic brain injury as risk factor for unprovoked epileptic seizures in a population based cohort with incident seizure cases. Method: In this population based case-control study, cases were 1885 patients with new onset unprovoked seizures included in the Stockholm Incidence Registry of Epilepsy. Controls, in total 15080-matched for gender, year of diagnosis, and catchment area- were randomly selected from the register of the Stockholm County population. Exposure was defined as a hospital discharge diagnosis of a traumatic head injury preceding the date of seizure onset. Odds ratios (ORs) were calculated to assess the risk of developing unprovoked seizures after hospital admission for various categories of head trauma defined by ICD codes from the Swedish Hospital Discharge Registry. Result: Odds ratio (OR) with 95% confidence interval (95%CI) for unprovoked epileptic seizures was 2.75 (2.193.45) after a discharge diagnosis of head trauma, 1.93 (1.462.55) after cerebral concussion and 8.86 (5.5514.15) after a more severe brain injury (contusion or traumatic intracranial hemorrhage). The risk of developing unprovoked seizures was highest during the first year, OR 5.42 (2.6111.27) after cerebral concussion and 30.53 (10.1292.09) after severe head injury. The risk declined gradually with time but still ten years after the trauma OR was 1.88 (1.272.79) for concussion and 2.44 (0.678.88) for severe head injury. Conclusion: We provide quantitative data on the risk of developing unprovoked seizures over time after brain trauma of different severity. Although highest the first year, the risk remains increased ten years after the trauma.
Basic Science 2 Wednesday, 03 October 2012

057 MTOR INHIBITION MODULATES EPILEPTOGENESIS, SEIZURES AND DEPRESSIVE-LIKE BEHAVIOR IN A GENETIC MODEL OF ABSENCE SEIZURES AND MILD DEPRESSION COMORBIDITY: A ROLE FOR INFLAMMATORY RESPONSES E. Russo*, R. Citraro*, A. Constanti, and G. De Sarro* *University of Catanzaro, Catanzaro, Italy; and UCL School of Pharmacy, London, UK
Purpose: The mammalian target of rapamycin (mTOR), a kinase regulating in the brain several physiological functions, seems to be involved in many CNS pathologies.1 Previous work in animal models of convulsive epilepsies, have suggested that mTOR modulators have beneficial antiepileptogenic effects. Method: We investigated the effect of some treatment schedules (earlychronic; sub-chronic; acute) with the mTOR inhibitor rapamycin, on the development of absence-seizures, seizure parameters and depressive-like behavior in WAG/Rij rats, a genetic model of absence epilepsy, epileptogenesis and mild-depression comorbidity. Furthermore, we studied the interaction between rapamycin and lypopholysaccharide (LPS) administration, which is known to aggravate absence seizures through increased inflammatory responses.3 Result: Rapamycin (early-chronic) exhibited antiepileptogenic properties also in this animal model; this effect was accompanied by pro-depressant effects. Both acute and sub-chronic (7day) treatments also had antiabsence properties, but the sub-chronic treatment produced contrasting anti-depressant properties in WAG/Rij rats not seen in Wistar rats. The rapamycin/LPS co-administration studies showed that rapamycin blocked/prevented LPS-dependent increase in absence-seizures, suggesting an anti-inflammatory-like protective action. Conclusion: Concluding, we demonstrated a novel rapamycin antiepileptogenic effect in a well-established absence epilepsy animal model; we suggest that this effect may be mediated by inhibition of inflammatory processes during epileptogenesis. The action of rapamycin and the role of mTOR on glial cell-mediated inflammation have never been studied before in epilepsy models; our experiments suggest new insights into this intriguing field which deserves to be further explored. References: 1 Garelick, Kennedy. Exp Gerontol. 2011 46:155. 2 Russo et al. Molecular Neurobiology. 2012. 3 Kovcs et al. Brain Res Bull. 2011 85:410.
056 EPILEPSY IN PRIMARY CEREBRAL TUMOURS: INTERIM RESULTS OF THE PERNO STUDY (PROJECT OF EMILIA ROMAGNA REGION ON NEURO-ONCOLOGY) R. Michelucci IRCCS of Neurological Sciences, Bellaria Hospital, Bologna, Italy
Purpose: The present study is aimed to define the clinical characteristics and outcome of tumoral epilepsy. Method: This study is a section of the PERNO project - a prospective registry of Primary Brain Tumours (PBT) in Emilia-Romagna Region spanning a three year period (20092011). All patients with epileptic seizures were included in the study and followed up on a regular basis. Seizure semiology, tumour location and histology, and response to treatments were analyzed. A consent form was obtained by each patient or responsible guardian. Result: Out of 610 PBT cases collected over the first two years, 114 (19%) had epileptic seizures. Sufficient data for analysis are available for 107 (67 male and 40 female) patients. Seventy one patients (66%) had malignant PBT, mainly involving the frontal (61%) or temporal (36%) lobes. Seizures were the first symptom in 80 cases (75%) and led to the diagnosis on PBT in most cases. Seizure types were focal motor (27%), somato-sensitive (11%) or tonic-clonic (26%). High seizure frequency at the onset was observed in 21% of cases and status epilepticus in 10%. Preliminary follow up data are available in 59 cases with malignant gliomas and show an initial drug-resistance of the seizures, which are usually halted only by surgical treatment. Conclusion: In this group of mainly malignant PBT the seizures appear lesion-dependant: they are the initial symptom of the tumour, herald its relapse and may be controlled only by surgery. This project was funded by the Research Program Regione-Universit 20072009 Area 1a Innovative Research.
058 DEVELOPMENTAL CHANGES IN THE NUMBER OF GABAERGIC NEURONS OF THE THALAMIC RETICULAR NUCLEUS IN ABSENSE EPILEPSY RATS ldy z*, and O. Kirazly * F. Onat*, S. Cavdar, H. Hacioglu*, S. Yy *Marmara University Medical School, Istambul, Turkey; and _ Koc University, Istanbul, Turkey
Purpose: Absence epilepsy models have shown that the production of seizures is related to an excess of GABAergic neurotransmission in the thalamus. The major source of GABAergic fibers to thalamic nuclei are from thalamic reticular nucleus (TRN). GABAergic neurotransmission in the thalamus and TRN plays a critical role in the generation and control of spike-and-wave discharge (SWDs) in absence epilepsy. This study aims to quantify the number of GABAergic neurons in the TRN developmentally (P10, P20, P30 and P60 days) of Wistar rat (n=5 for each developmental group) and compare the results with Genetic
19 Abstracts
Absence Epilepsy Rats from Strasbourg (GAERS; n=5 for each developmental group). Method: The intermediate TRN was removed from each animal and the GABAergic neurons were labelled using light-microscopy GABA immunohistochemistry. The disector method was used for the quantification and the data was statistically analysed. Result: The number of GABA labelled neurons in the TRN of Wistar animals showed reduction with increasing development (from P10 to P60), but was not statistically significant. However, the GAERS showed an increase in the number of GABA+iv neurons with increasing development between P10 and P60. The correlation of the number of GABA+iv neurons of each developmental group between Wistar and GAERS animals showed statistically significant difference in P30 (p=0.045) and P60 (p=0.011). Conclusion: The increase in the GABA+iv neurons, with development in GAERS, is likely to be related to the generation of SWDs or it may represent a compensatory response of the TRN to the thalamocortical circuitry in the absence seizures. Purpose: Temporal lobe epilepsy is characterized by a sclerosis of the hippocampus (Ammon's horn sclerosis) with a specific loss of pyramidal cells in CA1 and mossy cells in the hilus. Excitatory granule cells survive, but show a reorganization of their axonal connections. Their axons, the mossy fibres, loose their target cells due to mossy cell death and sprout backwards into the granule cell layer. It was suggested so far, that this leads to a recurrent, excitatory circuit. The aim of this study was to examine the target cells of mossy fibre sprouting, and determine whether mossy fibres impinge only on granule cells or also on other neurons, in particular inhibitory interneurons (basket cells). Method: Mossy fibres were traced with neurobiotin. In addition double immunohistochemistry against synaptoporin (mossy fibres) and parvalbumin (basket cells) was used. Synapses were examined with electron microscopy, labelled in addition with post-embedding gamma-aminobutyric-acid (GABA)-immunogold. Result: In human epileptic hippocampi sprouted mossy fibres innervated not only excitatory granule cells but also inhibitory interneurons. In addition, we show that the inhibitory axonal plexus around granule cells is preserved and that the number of inhibitory axon terminals exceeds the number of excitatory sprouted mossy fibre terminals on granule cells. Conclusion: Sprouting of mossy fibres does not simply results in an excitatory circuit of granule cells because recurrent mossy fibres also innervate inhibitory interneurons. This might lead to increased inhibition and synchronization of granule cells because the extensive inhibitory axonal plexus is preserved and shows an additional innervation through sprouted mossy fibres.
059 THE DISEASE-MODIFYING EFFECT OF CARISBAMATE IN THE LITHIUM-PILOCARPINE MODEL OF TEMPORAL LOBE EPILEPSY TRANSLATES INTO PRESERVED COGNITIVE FUNCTIONS J. Faure*, G. Akimana*, E. Marques*, J. Cassel*, and A. Nehlig *Universit de Strasbourg-CNRS, Strasbourg, France; and INSERM, Faculty of Medicine, Strasbourg Cdex, France
Purpose: Temporal lobe epilepsy (TLE) is one of the most frequent and disabling epilepsy forms. Since many patients are pharmacoresistant, new antiepileptic and antiepileptogenic drugs are needed. A recent study from our laboratory using a new drug, carisbamate (CRS), in the rat lithium-pilocarpine (li-pilo) model of TLE reported that CRS was neuroprotective and displayed disease-modifying effects in a subgroup of rats. These rats did not develop TLE but pharmacosensitive absence-like epilepsy (ALE). Here we studied the consequences of this neuroprotection on cognitive skills of ALE compared to TLE rats. Method: Lithium-pilocarpine or saline were administered to 55 adult rats. A 90 kg/mg dose of CRS or saline was given one hour after status epilepticus (SE) onset, repeated eight hours later and during six more days. The rats were video-monitored for two months and then their behavioral abilities were investigated. Tests including actography, plus-maze, beam-walking, Morris water maze, radial arm maze, double-H maze, and five-choice serial reaction time task were used. Result: The appearance of ALE occurred together with widespread neuroprotection in 8/25 CRS-treated rats. ALE rats that underwent li-pilo SE and CRS treatment did not present significant cognitive impairments compared to control rats. TLE rats, treated or not with CRS, performed significantly worse than control and ALE rats in all tests. Conclusion: The rats treated with CRS that developed ALE displayed nearly complete preservation of cognitive functions. Thus, treatment with this new drug has powerful disease-modifying effects that translate into both neuroprotection and impressive preservation of cognitive abilities.

p061 CHARACTERISING SEIZURE EVOLUTION IN PATIENTS WITH IDIOPATHIC GENERALIZED EPILEPSY USING A COMPUTATIONAL MODEL J. R. Terry*, A. Nevado-Holgado, F. Marten, and M. P. Richardson *University of Exeter, Exeter, UK; University of Oxford, Oxford, UK; University of Bristol, Bristol, UK; and King's College London, London, UK
Purpose: We propose that the dynamic evolution of EEG activity during epileptic seizures may be characterised as a path through parameter space of a computational model, reflecting gradual changes in underlying physiological mechanisms. Method: We use an evolutionary algorithm to estimate parameters of a computational model, according to the best fit obtained between the model output and specific features of the clinically recorded EEG waveform. We then evaluate the evolution of these parameters across the spike-wave discharge, by subdividing the discharge into individual spike-wave cycles and estimating parameters for each individual cycle. Result: We find that model parameters evolve consistently when different spike-wave discharges from an individual patient are considered. We further find that these evolutions vary between patients. Conclusion: Our study shows that variations in different underlying mechanisms can give rise to macroscopic dynamics (such as those recorded using EEG) that appear indistinguishable using standard clinical analysis tools. Our findings suggest that the evolution of model parameters is a useful tool for identifying subtle variations in EEG dynamics that may ultimately be useful for characterising epilepsy type and distinguishing between patients whom at present are given the same diagnosis.
060 SPROUTING MOSSY FIBRES INNERVATE EXCITATORY GRANULE CELLS AND INHIBITORY INTERNEURONS IN THE HIPPOCAMPUS OF PATIENTS WITH TEMPORAL LOBE EPILEPSY T. M. Freiman, K. Leicht, M. C. Mueller, J. Zentner, and C. A. Haas University Medical Centre Freiburg, Freiburg, Germany
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p062 COMPUTER ASSISTED ANALYSIS OF ELECTRICAL STIMULATIONS DURING STEREO-EEG RECORDINGS OF PRE-SURGICAL EPILEPTIC PATIENTS D. F. Boido*, S. Francione, V. Gnatkovsky*, and M. De Curtis* *Istituto Neurologico C. Besta, Milan, Italy; and Ospedale Niguarda C Granda, Milan, Italy
Purpose: Surgical intervention is a preferred choice for the treatment of patients suffering from drug-resistant focal epilepsy. Invasive studies with intracerebral electrodes are routinely performed when the boundaries of the epileptogenic zone (EZ) are not well defined. During this procedure, low-frequency bipolar stimulation (3ms-3mA pulses at 1 Hz for 30s) at each recording site is systematically performed to identify EZ and to functionally map the explored region. Nowadays the analysis of the recorded electrical responses to these stimulations is performed by experienced physicians, prevalently by visual inspection with time-consuming protocols. Method: We developed an original computer assisted algorithm to analyze evoked responses based on Labview; mono or bipolar responses of each tested couple of contacts are averaged and reliability assessed. Averaged responses selected on the base of their amplitude/area and features (peak amplitude, delay and area) are computed and stored. 3D-plot of all the idealized responses are made available for interactive inspection and quantitative measures. Result: Evoked responses are divided into three reliable consecutive phases. By comparing these phases it is possible to appreciate physiological and pathological connectivity between EZ and surrounding tissue. Conclusion: Our analysis suite proved to be useful to assist the evaluations of physicians in order to establish both the epileptic zone borders and the functional connectivity of the explored region. Moreover it is a valuable instrument for testing basic research hypothesis. down this hierarchical tree the decision rules guide the path either to the left or right child node. The exact split values, and which network characteristics are assigned to which nodes, is found by fitting a decision tree to given training data with known outcome labels. Our model had the highest accuracy if trees were based on random selected subsets of 5 network characteristics (out of 18). Accuracy was defined as the proportion of both true positives and negatives. Eventually, the lowest tree nodes direct to the binary outcome labels: partial epilepsy or control. After building the random forest diagnostic prediction model, we assessed the ability to differentiate between children with and without partial epilepsy using the areas under the Receiver Operating Characteristic curve (AUC). Since the AUC is typically considered to be optimistic when testing the diagnostic model on the same data, we used internal validation methods to correct for this. Result: Based on epileptiform EEG activity only, the diagnosis of epilepsy was supported with a sensitivity and specificity of 0.77 and 0.91 respectively. Power spectral density of EEG measures revealed no differences between patients and the control group. Furthermore, none of the individual network characteristics used in our prediction model, was significantly different between groups. In contrast, the prediction model had a sensitivity of 0.96 [95% confidence interval (CI): 0.781.00] and specificity of 0.95 [95%CI: 0.761.00] in correctly differentiating patients from controls. Best model performance was found for the broadband frequency, with an AUC of 0.74. Conclusion: Diagnostic accuracy in children with partial epilepsy is highly improved with a diagnostic prediction model combining functional network characteristics derived from multi-channel EEG recordings. Early accurate diagnosis is particularly valuable in children to inform and guide parents, to prompt treatment decisions and to limit the period of uncertainty and unnecessary risks.
p063 PARTIAL EPILEPSY IN CHILDREN CAN BE PREDICTED WITH FUNCTIONAL NETWORK CHARACTERISTICS E. G. A. L. Van Diessen*, W. M. Otte*, K. P. J. Braun*, C. J. Stam, and F. E. Jansen* *UMCU, Utrecht, The Netherlands; and VUmc, Amsterdam, The Netherlands
Purpose: In children referred with a possible diagnosis of partial epilepsies interictal electroencephalogram (EEG) is routinely performed but appears to be normal in many cases. In addition, evaluation of EEG abnormalities may be subjective and not very sensitive. In this study, we aimed to develop a multivariable diagnostic prediction model based on EEG functional network characteristics. Method: Routinely performed interictal EEG recordings of 35 children diagnosed with partial epilepsies, and of 35 children in whom the diagnosis epilepsy was excluded (control group), were analyzed (11 girls and 24 boys, mean age 10 3 years). Children with partial epilepsy were individually matched on gender and age with children from the control group. Neither patients nor controls had a developmental delay, a history of febrile seizures, generalized epilepsy or were on chronic anticonvulsive medicine. Resting-state EEG epochs, free of abnormal slowing or epileptiform activity, were selected to construct functional networks of correlated activity. We calculated multiple network characteristics often used in functional network epilepsy studies and included them as predictors in a diagnostic prediction model. We used the random forest classifier, a robust ensemble algorithm, as a model. The core of the random forest classifier is the binary decision tree, a data type that stores elements hierarchically in nodes. One node represented a network characteristic and is followed by two children nodes. In the process of building a binary decision tree, decision rules are formed (split values). If we follow a path
p064 SPATIO-TEMPORAL MODELS TO PREDICT AND CONTROL EPILEPTIC SEIZURE DYNAMICS G. Baier, M. Goodfellow, P. N. Taylor, Y. Wang, and D. J. Garry Manchester Interdisciplinary Biocentre, Manchester, UK
Purpose: EEG/MEG and fMRI studies have revealed complex spatiotemporal patterns of brain activity during focal-onset and generalised epileptic seizures. The origins and mechanisms of these phenomena at the macroscopic scale are important for the elaboration of new ways of treatment in epilepsy. For example, predictions of the effect of stimulation of the epileptogenic network, (as in closed loop seizure termination devices), require knowledge about how neuroanatomical location correlates with widespread abnormal activity. Here we demonstrate the use of computational modelling of spatio-temporal epileptic patterns to interpret clinical recordings of epileptic seizures. Method: Mathematical multicompartment models of large regions of brain tissue on the macroscopic scale are introduced to explain spatiotemporal features of distinct seizure types in terms of interacting excitatory and inhibitory neural populations. The model connectivity is based on connectivity data from diffusion-tensor imaging in humans. Bifurcation studies from nonlinear dynamics, and quantitative interrelation measures from multivariate data analysis are applied for model validation and parameter estimation. Model output is compared quantitatively to clinical EEG recordings. Result: Large-scale multi-compartment models can recreate generic features of epileptic EEG in humans. Specifically, the distribution of spatial heterogeneities and heterogeneities in the connectivity lead to robust patient-specific epileptic patterns while allowing for large inter-patient variability. Knowledge of the distribution of heterogeneities (e.g. in the cortex) allows to optimise stimulation protocols to suppress seizure activity. Conclusion: Spatiotemporal computational models of the macroscopic neuropathophysiology in humans are a novel tool to describe epileptic seizure dynamics and provide a rationale to design patient-specific predictions protocols for stimulation therapy.
21 Abstracts
p065 GLUTATHIONE TRANSFERASE POLYMORPHISMS IN PATIENTS WITH PROGRESSIVE MYOCLONIC EPILEPSY M. Ercegovac*, V. Coric, T. Simic, N. J. Jovic, D. V. Sokic, J. Jakovljevic, M. Kecmanovic, D. M. Nikolic**, S. M. Jankovic*, A. Savic-Radojevic, and M. Pljesa-Ercegovac *Clinic of Neurology, Clinical Center of Serbia, Belgrade, Serbia; Institute of Medical and Clinical Biochemistry, Faculty of Medicine, University of Belgrade, Serbia, Belgrade, Serbia; Clinic of Neurology and Psychiatry for Children and Youth, Belgrade, Serbia; Clinic of Neurology Clinical Center of Serbia, University of Belgrade, School of Medicine, Belgrade, Serbia; University of Biology, Belgrade, Serbia; and **Belgrade University Medical School, Belgrade, Serbia
Purpose: It has been reported that increased generation of free radicals or reduced activity of antioxidative defense mechanisms can cause some types of epilepsy and in addition, increases the risk of seizure recurrence. Glutathione transferases (GST) are superfamily of enzymes involved in detoxification and protection from oxidative damage. We hypothesized that genetic polymorphism of GSTM1, GSTT1, GSTA1, GSTO1and GSTP1may be associated with progressive myoclonus epilepsies (PME). Method: Genomic DNA was isolated from 26 patients with PME (Unverricht-Lundborg disease, Lafora body disease, Myoclonic Epilepsy with Ragged Red Fibers, ceroidlipofuscinosis) and 68 controls, matched for sex and age. The GSTA1, GSTO1 and GSTP1 genotypes were identified by PCR-restriction fragment length polymorphism method (RFLP). GSTM1 and GSTT1 genotypes were determined by multiplex PCR. Result: The frequency of GSTA1 low activity genotype TT was lower in patients with PME (3.8%) compared to controls (11.8%) (OR=0.27, p>0.05). Distribution of GSTM1 genotype did not significantly differ between cases and controls. Namely, GSTM1-null genotype was found in 51.5% controls and 53.8% cases (OR=1.10, p>0.05). Regarding GSTO1, low activity genotype AA was lower in patients with PME (3.8%) compared to controls (8.8%) (OR=0.5, p>0.05). The frequency of GSTP1 low activity genotype AG was lower in patients with PME (34.6%) compared to controls (44.1%) (OR=0.69, p>0.05). GSTT1-null genotype was found in 61.5% of patients with PME, which significantly differed from controls in which it was present in 25% (OR=4.80, p=0.001). Conclusion: It can be concluded that presence of GSTT1-null genotype increases the risk for progressive myoclonic epilepsy. psychological evaluation (Rey Auditory Verbal Learning Test, The ReyOsterrieth Complex Figure Test and Wechsler Memory Scale) focused to determine memory affection. We divided them into two groups: epilepsy with memory affection and epilepsy without memory affection and results were compared with those found in experiments using autopsy material. Result: Memory affection was found in 10 patients with MTLE (83%) and in 2 patients with TLE secondary to vascular lesion or tumor (18%). These patients demonstrated disturbances in short and/or longterm memory, including visual and/or verbal memory. Patients with memory disturbances demonstrated higher D1 receptors binding values (38%, p>0.05) in all cortical layers, when compared with patients without memory affection. No further comparisons were significantly different. Conclusion: Previous studies show that too much or too little stimulation of D1 receptors leads to working memory deficits. The present study indicates that patients with TLE showing high D1 receptor present a deleterious effect on memory. This effect may be associated with excessive D1 receptor stimulation. Study supported by CONACyT (project 98386).
p067 RARE CLINICAL FEATURE OF EPILEPSY, REPORT OF TWO CASES M. Nadeem Nishtar Medical College, Multan, Pakistan
Purpose: How Epilepsy causes abnormal behaviours that is false agressive. Method: Two patients 23 year and 27 year old with epilepsy were observed for three years, presented with false (pretended) agressive behaviour. When ever they want to flippant with other people, they fight and beat them. The intensity of fighting is low than original intensity. so in daily life activities, epilepsy patient present with false agressive behaviour. It is their way to flippant with others. The patients suffering from epilepsy have manifested a false aggressive behavior. This has been observed that such patients during showing aggressive behavior, do not want to give physical damage. Result: Although epilepsy causes abnormal behaviours, but abnormal false agressive behaviour is also caused by epilepsy. Conclusion: Abnormal false agressive behaviour is also caused by epilepsy.
p066 DOPAMINE RECEPTORS IN NEOCORTEX OF PATIENTS WITH TEMPORAL LOBE EPILEPSY: CORRELATIONS WITH MEMORY DISTURBANCES M. P. Mata Mendoza*, J. M. Cisneros-Franco, A. R. Martnez, M. A. Alonso Vanegas, and L. L. Rocha* *Center for Research and Advanced Studies, Distrito Federal, Mexico; and Instituto Nacional de Neurologa y Neurociruga, Distrito Federal, Mexico
Purpose: To correlate abnormalities in binding to D1 and D2 receptors as well as dopamine transporter in temporal cortex with memory disturbances of surgically treated patients with pharmacoresistant temporal lobe epilepsy (TLE). Method: By autoradiography experiments, D1 and D2 receptors and dopamine transporter binding was evaluated in temporal neocortex obtained from autopsies (n=8) and patients with TLE associated with mesial sclerosis (MTLE, n=12) and with TLE secondary to tumor or vascular lesion (n=11). The values obtained were correlated with neuro-
p068 UP-REGULATION OF METHYL CPG BINDING PROTEIN-2 IN INTRACTABLE TEMPORAL LOBE EPILEPSY PATIENTS AND EXPERIMENT ANIMALS Y. Chen, S. Tao, and J. Li Chongqing, China
Purpose: Methyl CpG binding protein-2 (MeCP2) is a multifunctional nuclear protein. MeCP2 plays an important role in regulating dendritic morphology, mediating synaptic transmission, spontaneous neurotransmission and short-term synaptic plasticity in the central nervous system (CNS). Our aim was investigate the expression of MeCP2 mRNA and protein in intractable temporal lobe epilepsy patients and experiment animals. Method: Using reverse transcription polymerase chain reaction (RTPCR), immunohistochemistry and double label immunofluorescence, we detected MeCP2 expression in 35 temporal neocortex tissue samples from patients with intractable temporal lobe epilepsy (TLE) and 14 histological normal temporal lobe tissue samples from the control group. We also examined the timing of MeCP2 expression in the hippocampus and
22 Abstracts
adjacent cortex of rats with temporal lobe epilepsy (lithium chloride-pilocarpine model) at 1, 2, 7, 14, 30, and 60 days after kindling and the control group. Result: MeCP2 is expressed mainly in the nucleus of neurons, not expressed in astrocyte. MeCP2 expression was significantly higher in the TLE group and experiment animals group as compared with the control group. The expression of MeCP2 in the rat hippocampus and adjacent cortex after seizures gradually increased during the acute period (1, 2 days) and the latent period (7.14 days) but decreased during the chronic period (30.60 days). Conclusion: The up-regulation of MeCP2 in intractable TLE patients and experiment animals suggest that MeCP2 may involved in the pathogenesis of TLE.
Mario Negri Institute for Pharmacological Research, Milano, Italy

Purpose: We studied the role of TLR4 and RAGE in epileptogenesis using a mouse model of mTLE. These receptors are activated by endogenous proinflammatory danger signals, such as High Mobility Group Box 1 released in injured brain and previously shown to play a pivotal role in ictogenesis (Maroso et al, Nature Med, 2010). Method: C57BL/6 adult male wild-type mice (WT) were intrahippocampally injected with kainate to induce status epilepticus (SE) and spontaneous recurrent (drug-resistant) epileptic activity. Age and gendermatched C57BL/6 TLR4 and RAGE knock-out (KO) mice were similarly treated. We compared mice for epilepsy development, cognitive performance, neuropathology and neurogenesis (doublecortin, DCX staining) Result: SE duration and severity and the onset time to spontaneous epileptic activity were similar in all groups. However, the frequency of epileptic events was significantly reduced by 60% and 30% in TLR4 and RAGE KO, respectively, vs WT mice. Epileptic mice of either genotype and WT epileptic mice had similar memory impairment, comparable cell loss (except in CA1 where RAGE KO showed increased neurodegeneration) and granule cell dispersion. DCX staining was absent in epileptic WT and RAGE KO mice; notably, DCX positive cells were present in epileptic TLR4 KO mice similarly to non epileptic control mice. Conclusion: Activation of RAGE and TLR4 signaling by endogenous danger signals significantly contributes to the severity of epilepsy developing after SE. These receptors differentially affect the fate of newly generated neurons and CA1 cell survival in epileptic tissue. Our findings highlight new molecular mechanisms involved in epileptogenesis.
p069 NETWORK TOPOLOGY AND SEIZURE INITIATION IN IDIOPATHIC GENERALISED EPILEPSY M. P. Richardson*, F. A. Chowdhury*, T. Fitzgerald, O. Benjamin, R. D. Elwes, L. Nashef, and J. R. Terry *King's College London, London, UK; University College London, London, UK; Bristol University, Bristol, UK; King's College Hospital, London, UK; and University of Exeter, Exeter, UK
Purpose: We examined whether brain network topology in normal interictal EEG differed between patients with IGE and normal controls. We then examined a dynamic model of seizure initiation based on these networks, attempting to relate altered network structure in IGE with a greater liability to generate seizures. Method: We studied 35 patients and 40 normal controls, using EEG (21 scalp electrodes, sampling 256Hz, filtered 0.370Hz). Phase synchrony between EEG electrodes was assessed in 5 frequency bands using EEGlab. Unweighted undirected graphs were constructed for each subject and band; nodal degree variance (D) and small world index (SWI) were calculated for each network and compared between groups. Using a phenomenological model of seizure initiation, we examined the exit time in the presence of noise, which we equate with seizure frequency. Result: Using nonparametric statistical tests and Bonferroni correction for multiple comparisons, we found that D was lower in controls than in patients in the beta and gamma bands (beta: p=0.040; gamma: p=0.032). SWI was greater in controls than patients in the beta band (p=0.031). We found that network structure in patients correlates with shorter escape times relative to network structures from controls, especially in beta and gamma bands. Conclusion: EEG networks of functional connectivity in beta and gamma bands differ significantly between IGE and normals. Networks based on patient data generate seizures more readily than normal networks in a dynamic model.
p071 ICTAL TACHYCARDIA PREVALENCE AND COMPARISON WITH OTHER FACTORS WHICH INFLUENCE CARDIAC RATE R. M. Mcguire, W. Liao, K. Eggleston, J. Begnaud, and M. T. Bunker Cyberonics, Inc., Houston, TX, USA
Purpose: Literature suggests that heart rate changes may precede or occur concurrently with some seizure types. Monitoring heart rate, therefore, may be a useful diagnostic in seizure prediction or detection in some patients with epilepsy. Method: We analyzed simultaneously recorded EEG and ECG data from a large patient population during an epilepsy monitoring unit stay to assess the prevalence and frequency of ictal tachycardia. A seizure was classified as exhibiting ictal tachycardia if the heart rate reached at least 100 bpm during the ictal period, and in comparison to the pre-ictal period, the heart rate increased by either 35 bpm or 55%. Additionally, we compared heart rate changes associated with seizures to those measured during moderate exercise. Result: Annotated seizures with complete clinical diagnoses from sixtyfour patients were analyzed. Thirty-four of these patients (53%) had at least one seizure that met the definition of ictal tachycardia. Further, 50% of all seizures (84 of 167) within this subset of patients (n=34) exhibited ictal tachycardia. Compared with moderate exercise, seizures defined as ictal tachycardia exhibited higher magnitude and more rapid changes in cardiac rate. Conclusion: The data indicate that ictal tachycardia is prevalent in patients that primarily exhibit complex partial seizures originating in the temporal lobe. The results suggest that heart rate changes associated with seizures may be distinguishable from other factors which affect cardiac rate such as exercise. Therefore, monitoring heart rate may serve as a viable diagnostic for indicating seizure onset or logging seizure occurrence.

p070 SIGNIFICANT INVOLVEMENT OF TOLL-LIKE RECEPTOR 4 (TLR4) AND RECEPTOR FOR ADVANCED GLYCATION END PRODUCTS (RAGE) IN EPILEPTOGENESIS IN AN EXPERIMENTAL MODEL OF MESIAL TEMPORAL LOBE EPILEPSY (MTLE) V. Iori, M. Maroso, R. Vertemara, M. Carli, T. Ravizza, and A. Vezzani
23 Abstracts
p072 CHARACTERIZATION OF MULTIPLE MITOCHONDRIAL DNA DELETIONS IN SCLEROTIC HIPPOCAMPUS OF PATIENTS WITH TEMPORAL LOBE EPILEPSY W. S. Kunz, G. Zsurka, and V. Peeva University Bonn, Bonn, Germany
Purpose: In this work we addressed the molecular cause for the mitochondrial dysfunction in hippocampal subfields of patients with hippocampal sclerosis, one of the most common forms of therapy-resistant temporal lobe epilepsy. Method: Applying long-range PCR, single molecule PCR and a next generation sequencing approach we identified, quantified and mapped mitochondrial DNA deletions in hippocampal subfields of patients with temporal lobe epilepsy, who underwent epilepsy surgery. These mitochondrial DNA rearrangements are an accepted cause for mitochondrial dysfunction in various neuromuscular disorders and aging. Result: The deletion loads approached in the CA3 subfield and the dentate gyrus of patients with hippocampal sclerosis 28% of total mitochondrial DNA content. A major fraction of the detected deletions had the 3 breakpoint at a hot spot around np 16070 implying ROS-caused mitochondrial DNA double strand breaks as potential mechanism of deletion formation. High levels of deleted mitochondrial DNA appear to correlate with the presence of cytochrome c oxidase-negative and succinate dehydrogenate-positive neurons in the CA3 and CA4 hippocampal subfields. Hippocampal samples from age-matched patients with epilepsy due to lesions in the temporal lobe did not contain elevated levels of deleted mitochondrial DNA. Conclusion: Dysfunction of mitochondrial oxidative phosphorylation in the epileptic focus of patients with Ammon's horn sclerosis appears to be related to clonal expansion of specific types of deletions of mitochondrial DNA generated very likely by increased oxidative stress. This mechanism is proposed to be relevant for seizure generation in the sclerotic hippocampus of patients with temporal lobe epilepsy and Ammon's horn sclerosis. Result: Our results showed that TNF and NFKB1 were significantly upregulated in TLE+HS patients (p=0.0035 and p<0.02, respectively) while KL expression was significantly downregulated (p<0.02). Conclusion: This is the first study relating KL with HS and epilepsy. Our data suggest that TNFa might affect KL expression in hippocampus. As a multifunctional protein, our finding on KL downregulation in TLE+HS patients opens several possible avenues of research that will help us to understand the complex pathophysiology in HS.
p074 EPILEPSY AND SLEEP; A PERFECT MARRIAGE!!! I. J. Poddar, and K. M. Haridas KMC, Kolkata, India
Purpose: Older studies of patient-reported seizure precipitants have not evaluated whether different epilepsy syndromes are differentially affected with pricipitating factors mainly sleep. Method: Patients of a tertiary-care epilepsy center were consecutively surveyed with the use of a standardized questionnaire that lists precipitants that might trigger or exacerbate seizures . Patients were classified into epilepsy syndromes according to International League Against Epilepsy criteria. Age and gender within groups defined by major precipitants were compared. Pearson's correlation was performed to evaluate common patterns of precipitants Result: Of 500 patients, 58% cited at least one precipitant. In order of frequency, stress (22%), sleep deprivation (28%), sound and light flashes (26%), fever (08%), fatigue (03%) and others (13%). Stress, light and sound flashes, and sleep deprivation positively correlated. Rankings of precipitants varied within epilepsy syndromes, with patients with temporal lobe epilepsy citing sleep infrequently compared with patients with other epilepsy syndromes. Menstrual effects were ranked highly within major precipitants among women over age 14 and were especially noted by women with temporal lobe epilepsy (34%). Conclusion: Many patients with epilepsy identify a precipitant that triggers or exacerbates seizures. The high correlation of stress, sleep deprivation, and fatigue suggests that they act through common mechanisms to worsen seizure control. Through identification of the effect of both endogenous and exogenous precipitants among syndromes, more research and counseling can be directed to specific precipitants.
p073 DIFFERENTIAL MRNA EXPRESSION OF TUMOR NECROSIS FACTOR AND KLOTHO IN TEMPORAL LOBE EPILEPSY PATIENTS WITH HIPPOCAMPAL SCLEROSIS M. A. Teocchi, A. E. D. Ferreira, E. Oliveira, H. Tedeschi, and L. DSouza-Li University of Campinas, Campinas, Brazil
Purpose: Previous research in animal seizure models point to the pleiotropic cytokine TNFa as an important effector/mediator of neuroinflammation and cell death. One of the primary events in seizure induced cell death is the excessive release of glutamate with a consequent increase in intracellular calcium influx. Klotho (KL), originally identified as an antiaging protein, is emerging as an important calciophosphoregulatory hormone. Its cerebral function is unclear; however, the klotho knockout mouse exhibits a phenotype resembling human aging presenting neural degeneration and a reduction of synapses in the hippocampus. Moreover, it was demonstrated that TNFa down-regulates KL through NF-jB in animal models of chronic kidney disease and colitis. Our objective is to prove that a similar downregulation occurs in temporal lobe epilepsy patients with hippocampal sclerosis (TLE+HS). Method: We evaluated TNF, KL and NFKB1 relative mRNA expression levels by Reverse Transcription quantitative PCR in resected hippocampal tissue samples from 14 TLE+HS patients and compared them to four post mortem controls. Two pairs of reference genes were used: GAPDH and HPRT1 (classical) and ENO2 and TBP (alternative).
p075 NMDAR1 EXPRESSION IN THE TEMPORAL LOBE FROM INTRACTABLE EPILEPSY PATIENTS Z. Wang, W. Lin, and L. Lu The First Hospital of Jilin University, China
Purpose: In order to study NMDAR1 in the temporal lobe from intractable epilepsy patients. Method: Cortical temporal lobe brain were collected from 20 patient with intractable epilepsy and 10 patients with traumatic brain injury . the NMDAR1 expression were detected by immunohistochemistry and western blot in both group. Result: The results showed that expression of NMDAR1 in the experimental group was higher than the control group (p<0.001), the absorbance value of NMDAR1 protein strip observed from intractable epilepsy patients was 0.41750.2321 compared to 0.24120.1458 in the control group (p<0.005). Conclusion: Expression of NMDAR1 in the temporal lobe from intractable epilepsy patients was higher than the control group
24 Abstracts
p076 ARE GLUTAMINE SINTHETASE EXPRESSION LEVELS ASSOCIATED WITH MESIAL TEMPORAL LOBE EPILEPSY WITH HIPPOCAMPAL SCLEROSIS? A. Martins Da Silva*, R. Branco, B. Leal, R. Rangel*, C. Carvalho, A. Bettencourt, J. Chaves*, A. Santos, T. Magalhes, M. Honavar, M. Melo Pires*, B. Martins Da Silva, and P. P. Costa *Hospital de Santo Antnio - Centro Hospitalar do Porto, Porto, Portugal; Instituto Cincias Biomdicas Abel Salazar, Porto, Portugal; Instituto Medicina Legal - Delegao Porto, Porto, Portugal; and Unidade Local de Sude Matosinhos - Pedro Hispano, Matosinhos, Portugal
Purpose: Glutamate is an essential excitatory neurotransmitter involved in diverse brain functions. Excess of extracellular glutamate can lead to excitotoxicity and subsequent cell death. The glutamatergic system is regulated by glutamine synthetase (GS), an enzyme responsible for glutamate metabolism in astrocytes. Abnormalities in this pathway have been implicated in the onset and progression of several neurological diseases including mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). In this study, we evaluated the expression levels of GS in the surgical removed lesions from hippocampal tissue and in the adjoining temporal cortex of MTLE-HS patients. Method: Twenty two patients with refractory MTLE-HS submitted to surgery were studied. Surgical specimens of hippocampus (lesional and peri-lesional cortical area) were collected. These samples were compared with nine autopsy controls without Known neurological disorder. GS expression levels were quantified by Real-Time PCR. Result: The expression levels of GS were similar in the hippocampus and temporal cortex of MTLE-HS patients when compared to similar data from matched healthy controls. Conclusion: Our results demonstrate that GS expression levels are not altered in MTLE-HS. This absence of differences does not exclude the hypothesis of abnormalities in GS at protein and functional level. For this reason, complementary studies are being performed to evaluate the protein/activity of GS and to elucidate the role of glutamatergic system in the aetiology of MTLE-HS. Supported by a FCT grant PIC/IC/83297/2007 levels of EAAT1 in the surgically removed lesions (hippocampus and the adjoining temporal cortex) of MTLE-HS patients. Method: EAAT1 expression levels in the hippocampus (lesional and peri-lesional cortical area) were quantified by Real-Time PCR in 22 MTLE-HS patients submitted to surgery and compared with 9 autopsy controls with no history of neurological disorders. Result: EAAT1 was overexpressed in both the hippocampus (p=0.008) and in the temporal cortex (p=0.018) of MTLE-HS patients when compared to autopsy controls. Conclusion: Our results demonstrate that the glutamatergic pathway is altered in the hippocampus of MTLE-HS patients. Additionally, EAAT1 overexpression in adjoining cortex suggests that this area could be involved in disease progression. EAAT1 overexpression could be explained by a compensatory mechanism to overcome the accumulation of glutamate in epileptic focus. Supported by a FCT grant PIC/IC/83297/2007.
p078 DEVELOPING A MULTI-MODAL DEVICE FOR NONEEG, EXTRAMURAL NOCTURNAL SEIZURE MONITORING J. Van Andel TeleEpilepsy Research Consortium; UMCU, Kempenhaeghe, SEIN, Utrecht, The Netherlands
Purpose: In epilepsy, 25% of patients have regular, intractable seizures, especially children with epilepsy syndromes and patients with gross brain abnormality and cognitive impairments. About half of seizures are at night, posing problems in these vulnerable patient groups depending on caregivers not sleeping in the same bed. A reliable seizure detection and alert system will provide a major step in patient safety, quality of life and disease management, however presently this is lacking. A new multimodal device using an optimized combination of nonEEG sensors is developed. Based on preliminary studies 4 modalities were selected: audio, automated video frame analysis, ECG and 3D-accelerometry. Method: A diagnostic study design is used to define optimal combinations of algorithms analyzing the 4 modalities in the target population: children <18, and mentally impaired adolescents and adults with major nocturnal seizures. The multimodal device is tested in an in-hospital setting in 100 patients, simultaneously with the gold standard of clinical video-EEG. Modern methods of classification and regression analysis are applied to define optimal sets of joint thresholds for the modalities. The aim is to achieve a high detection rate for seizures, with a minimum of false alarms in seizure free periods. Patient factors are taken into account, potentially allowing for tuning thresholds to individual patients. Result: To demonstrate our method, an interim-analysis of results will be presented in September 2012. Conclusion: In this study, the validity of a newly developed device for home detection of epileptic seizures during sleep in patients with major nocturnal seizures is tested.
p077 EXCITATORY AMINO ACID TRANSPORTER 1 EXPRESSION IN HUMAN MESIAL TEMPORAL LOBE EPILEPSY WITH HIPPOCAMPAL SCLEROSIS B. Leal*, R. Branco*, R. Rangel, A. Bettencourt*, C. Carvalho*, J. Chaves, A. Santos, T. Magalhes, M. Honavar, M. Melo Pires, A. Martins Da Silva, P. P. Costa*, and B. Martins Da Silva* *Instituto Cincias Biomdicas Abel Salazar, Porto, Portugal; Hospital de Santo Antnio - Centro Hospitalar do Porto, Porto, Portugal; Instituto Medicina Legal - Delegao Porto, Porto, Portugal; and Unidade Local de Sude Matosinhos - Pedro Hispano, Matosinhos, Portugal
Purpose: Glutamate is the predominant excitatory neurotransmitter in the Central Nervous System. Its excessive accumulation causes an excitotoxic process that can result in cell death. Glutamate transporters play an important role in regulating glutamate extracellular concentrations. EAAT1 (Excitatory Amino Acid Transporter 1) is a glutamate transporter highly expressed in astrocytes. Dysfunction in EAAT1 has been implicated in the onset of several neurological disorders including epilepsy. However, controversy exists on whether EAATs expression is altered in patients with Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis (MTLE-HS). To clarify this controversy we evaluated the expression

p079 THE RISK OF SEIZURES IN PROGRESSIVE MULTIPLE SCLEROSIS O. W. Howell*, R. Nicholas, D. Gveric, M. I. Rees*, F. Roncaroli, and R. Reynolds *Swansea University, Swansea, UK; and Imperial College London, London, UK
25 Abstracts
Purpose: Cortical pathology is thought to contribute to motor, sensory and cognitive difficulties experienced by people with multiple sclerosis (MS). The extent of cortical and deep grey demyelination is often greater than that of the white matter, and it has been shown that inflammation of the grey matter and subcortical areas is associated with an increased risk of epilepsy. We hypothesise that inflammation, demyelination and neuroaxonal damage, cardinal features of long-standing progressive MS, will likely contribute to an increased risk of seizures. Method: We compared clinical disease milestones and pathology with seizure status from a cohort of 115 cases of secondary progressive MS (73 female, disease duration: 26.510.8yrs; age died: 57.413.1yrs). Result: Twenty two (19%) cases had at least a single seizure event, and these cases differed to the MS group without seizures with respect to: a younger age at progression (37.89.1 vs 42.610.2yrs, p=0.045), younger age at wheelchair (41.410.3 vs 46.512.6yrs, p=0.035), younger age at death (51.511.6 vs 58.813.2yrs, p=0.018) and shorter duration of the progressive phase (12.76.3 vs 16.16.8yrs, p=0.05), but not total disease duration (p=0.127). Seizures risk was independent of gender or overlying meningeal inflammation (p>0.3). A more severe clinical disease reflected the increased severity of global neuropathology (mean rating 6.81 vs 5.62.3, p=0.005) and reduced brain weight (1082135g vs 1173134g, p=0.01) for the MS plus seizure cohort at post-mortem. Conclusion: Our analysis suggests that seizure occurrence in MS is influenced by disease course and likely reflects the accumulation of myelin and neuroaxonal damage in the cortex. les electronic health record innovative (it is designed to be compatible to the widely recognized HL7 Reference Information Model architecture), the ongoing work and results from the area of computer-based video analysis for detecting and quantifying epileptic seizures, will be presented.
p081 DNA METHYLATION PROFILING REVEALS DIFFERENTIAL METHYLATION PATTERNS CORRELATED WITH GENE EXPRESSION IN HUMAN EPILEPSY L. Wang, and X. Wang The First Affiliated Hospital of Chongqing Meidical University, Chongqing, China
Purpose: Few studies have addressed whether abnormal DNA methylation contributes to differential gene expression in epilepsy. This study aimed to define differential DNA methylation patterns in drug-refractory epilepsy patients and to investigate the role of DNA methylation in epileptogenesis. Method: We evaluated DNA methyltransferase 1 (Dnmt1) and Dnmt3a expression in brain tissues of epileptic patients and then performed DNA methylation profiling in brain tissues from epileptic and control patients (n = 3 of each) via methylated-cytosine DNA immunoprecipitation microarray chip. Differentially methylated loci were validated by bisulfite sequencing-PCR, and the mRNA levels of candidate genes were evaluated by reverse transcriptase PCR. Result: We found that Dnmt1 and Dnmt3a was up-regulated in the brain tissues of epileptic patients. We also found 224 genes that showed differential DNA methylation between epileptic patients and controls. These genes included those involved in the regulation of Rho, microtubulebased processes and mitogen-activated protein kinase scaffold activity. Among the seven candidate genes, three showed clear transcriptional regulation by DNA methylation. TUBB2B and ATPGD1 exhibited relatively hypermethylated promoters and decreased mRNA levels, whereas HTR6 displayed a relatively hypomethylated promoter and higher mRNA levels in the epileptic samples. Conclusion: Our findings suggest that certain genes become differentially regulated by DNA methylation in epilepsy.
p080 HERCULES: DEVELOPING AN INTEGRATED HEALTH CARE SCHEME, BASED ON BIOMEDICAL GENETICS, ADVANCED BIOMEDICAL INFORMATICS AND COMPUTER VISION FOR EARLY DIAGNOSIS, MONITORING AND TREATMENT OF CHILDREN WITH NEUROLOGICAL DISORDERS IN GREECE. PILOT APPLICATION IN ABSENCE LIKE SEIZURES P. Vorgia*, M. Pediaditis, V. Kritsotakis, H. Dimitriou*, M. Tsiknakis, S. Voutoufianakis, V. Danilatou, D. Kafetzopoulos, and D. Fotiadis *Medical School, University of Crete, Heraklion Crete, Greece; FORTH, Heraklion Crete, Greece; FORTH, Heraklion, Greece; Venizelion General Hospital, Heraklion Crete, Greece; and University of Ioannina, Ioannina, Greece
Purpose: Epilepsy is one of the most common chronic neurological disorders. Children and adolescents with active epilepsy in Europe are estimated at 0.9 million, meaning that 1% of the population of children is affected. A significant proportion of them, reaching 30%, are pharmacoresistant. Resistance to treatment has a heavy burden on children's quality of life. The Hercules project aims to the development of an integrated healthcare and research scheme specified for Childhood Neurological Disorders, and mainly for epilepsy. Method: The main idea is to integrate medical, behavioral (motionrelated) and genetic information in order to build innovative tools and networks for providing state-of-the-art quality of care. This health care improvement will be achieved through better disease classification, knowledge discovery and invention of decision support systems. The overall architecture of the Hercules project includes: (a) the development of a biobank, (b) the development of an electronic health record, (c) the acquisition and installation of a state-of-the art videoelectroencephalogram monitoring system for the detection and quantification of epileptic seizures. Result: Absence like seizures are the first ones to be studied. Conclusion: The information related to the technological requirements, the architectural design, the functional specifications that render Hercu-
p082 EVOKED HIGH FREQUENCY OSCILLATIONS IN THE HUMAN HIPPOCAMPAL FORMATION D. Fabo*, E. Toth, A. Sakovics*, L. Er} oss, and I. Ulbert *Natl. Institute for Neuroscience, Budapest, Hungary; Peter Pazmany Catholic University, Budapest, Hungary; National Institute of Neuroscience, Budapest, Hungary; and Institute for Psychology, Hungarian Academy of Sciences, Budapest, Hungary
Purpose: Cortical electrical stimulation (CES) is an approved therapy for drug resistant focal epilepsies. Despite the advanced usage of intracortical evoked potentials (iEP) the neuronal circuit mechanisms of CES are poorly understood. We examined the effect of CES under general anesthesia in the hippocampal formation (HF) of five temporal lobe epilepsy (TLE) patients. Method: We used laminar multielectrodes to record local field potential (LFP), multiple unit activity (MUA), current source density (CSD) and spectral activation of iEPs elicited by singe pulse (SPS) and train (TrS), subdural cortical electrical stimuli (0.1ms; 515mA; 0.5Hz and 50Hz). High frequency oscillation packages, ripples, were detected by semi automatic methods. Result: High frequency oscillations (ripple and fast ripple) was associated to bi- or tri-phasic iEPs were elicited by SPS in the HF stimulating the temporo-basal areas. The central frequencies of different ripples were
26 Abstracts
100, 150 and 250Hz. Ripple activity was elicited with high probability (6098%). Similar but higher power ripples and fast ripples associated to after discharges after TrS. Conclusion: We conclude that CES iEPs contain abundant amount of ripples and fast ripples. The evoked ripple activity raises questions about the long-term effects of CES in the temporal lobe. TLE the down-regulated limk1 did not correspond with up-regulated plimk1. Conclusion: These results may reflect limk1 expression as substance basis is not a leading reason for affecting p-limk1 expression in human TLE, probably impressed by some activators of limk1, such as P21-activated kinase (PAK) and Rho-associated coiled-coil domain kinase (ROCK). These indicated limk1 and p-limk1 are likely to involve in pathogenesis of epilepsy by affecting cytoskeletal reorganization, and different predominant reasons may affect cytoskeletal reorganization and synaptic plasticity by affecting at different stage and severity of TLE.
p083 THE EXPRESSION OF MIR-132 ASSOCIATED WITH CREB IN EPILEPSY H. Wang The Second Affiliated Hospital Chongqing Medical University, Chongqing, China
Purpose: Temporal lobe epilepsy (TLE) is a common and often neurological disorder. TLE is often associated with the formation of excitability of abnormal circuit. MicroRNAs (miRNAs) are small non-coding RNAs that play essential roles in synaptic development, synaptic plasticity and cytoskeletal reorganization. Mir-132 that is a CREB-adjusting protein can increase density and length of dendritic spines, and increase frequency of miniature excitatory post-synaptic currents (mEPSCs) and decrease synaptic depression through inhibiting P250GAP that is a family number of Rho GTPase. Method: We in a rat model of epilepsy and in the human TLE separately measured mir-132 expression with real-time PCR and P-CREB that is an active form of CREB with western blot and immunohistochemistry technology. Result: Were that mir-132 is up-regulated at 24 h after initiation of the seizure in the rat model of TLE, and this coincided with up regulation of P-CREB expression. But at the rest of time points in the rat model of epilepsy and in the human TLE mir-132 is down-regulated, and this does not coincide with up regulation of P-CREB expression. Conclusion: These results show that P-CREB is likely to partly adjust mir-132 expression especially at the acute stage of epilepsy, but at chronic stage and in the human TLE mir-132 is likely to be affected by other factors. The change of up regulation and down regulation of mir132 is likely to be easier to form the excitability of abnormal circuit. Similar to the alternate use of latrunculin A and jasplakinolide induce epileptic seizures and a long-term increase in neuronal excitability.
p085 A MATHEMATICAL MODEL OF EPILEPSY: SYNAPTIC REGULATION ACTS AS AN ANTI-EPILEPTIC REGULATORY MECHANISM A. Peterson*, I. Mareels*, and M. Cook *University of Melbourne, Parkville, Vic., Australia; and The University of Melbourne, Melbourne, Australia
Purpose: The spread of seizure-like behaviour through the cortex is facilitated not only by hyper-excitable, hyper-synchronous neuronal population firing, but by overcoming the regulatory mechanisms of the brain, such as feedback, feed-forward and surround inhibition. These control mechanisms attempt to stabilise such pathological behaviour. We suggest an additional network regulatory mechanism in the form of a shunting effect based on endogenous synaptic regulation of input currents, an important neurophysiological function whose mechanism is difficult to incorporate in macroscopic models of brain dynamics. Method: A mathematical neural model is modified to include more realistic synaptic dynamics as opposed to previous models which use simplified synapses. This is a more realistic description of synaptic behaviour that has a significant effect on the overall network dynamics. A nonlinear summation (as opposed to a linear one) of the synaptic currents is introduced that incorporates local feedback from the membrane potential and an active time constant that varies inversely with the amount of input or drive to the network. The result is a more physiologically detailed description of the synaptic current produced by post-synaptic potentials. The states of the new system are found and an analysis is performed. The stability of the system is determined and an exploration of pertinent parameters, namely the network input and network balance (inhibitory/ excitatory), highly relevant to epileptogenesis is produced. These results are then compared to that of the original model with simplified synapses and the differences interpreted physiologically. Result: The dynamics and oscillatory properties of the more detailed model differ significantly from the previous model. This is largely due to the shunting effect of synaptic regulation, which acts as a network control mechanism. In particular, within the same parameter ranges for the network input and balance, oscillatory behaviour is suppressed. Conclusion: Synaptic regulation of network behaviour is an important neuro-physiological function whose mechanisms of synaptic current transmission and homeostatic tendencies should not be neglected in neural models of epilepsy, particularly when examining seizure localisation, spread and termination.
p084 THE EXPRESSION OF LIM KINASE1 AND ASSOCIATED ACTIVE FORM IN HUMAN AND RAT TEMPORAL LOBE EPILEPSY X. Yang, and X. Wang The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
Purpose: Epilepsy is a common and often neurological disorder. Epilepsy is often associated with formation of excitatory circuit, including abnormal form of dendrites and axons, but the exact mechanism remains unknown. Lim kinase1 (limk1) is an associated cytoskeletal protein, phosphorylated at the site of threonine 508, and then by phosphorylating cofilin affects dynamics of cytoskeleton and synaptic plasticity. So we infer that limk1 and its active form phospho-limk1 (p-limk1) may involve in the pathogenesis of epilepsy by affecting cytoskeletal reorganization and synaptic plasticity. Method: Here, we investigated expression of limk1 and p-limk1 by immunohistochemistry and western blot analysis in a rat model of temporal lobe epilepsy (TLE) as well as in human TLE. Result: In the rat model of TLE, p-limk1 expression was up-regulated at 6h, 72h, 30d and 60d after initiation of the seizure, corresponding with up-regulated limk1 at 6h, 72h, 7d, 14d, 30d and 60d. Moreover, in human
p086 DEEP BRAIN STIMULATION EARLY DURING EPILEPTOGENESIS MODIFIES DISEASE PROGRESSION IN THE HIPPOCAMPUS B. Van Nieuwenhuyse*, K. Vonck*, R. Raedt*, A. Meurs*, W. Wytse, and P. A. J. M. Boon* *Ghent University, Ghent, Belgium; and Swammerdam Institute of Life Sciences, Amsterdam, The Netherlands
27 Abstracts
Purpose: Despite promising DBS results, the mechanism of action, the long-term effects and the possible anti-epileptogenic properties of DBS remain undetermined. In this animal experimental study, we evaluated the effect of DBS on the development of spontaneous seizures in the kainic acid rat model. Method: Rats were implanted with a bipolar DBS electrode in the right hippocampus and a bipolar EEG recording electrode in both hippocampi. 24 hours after kainic acid (KA) induced status epilepticus (SE), one group (n=6) was subjected to short term DBS (ST-DBS) (poisson distributed stimulation (PDS), 130 PPS, 100ls PW, 100lA) of 1 week, a second group (n=7) was subjected to long term DBS (LTDBS) (PDS, 130 PPS, 100ls PW, 100400lA) of 10 weeks. A control group (n=9) received sham stimulation (SHAM). EEG was recorded continuously during 14 weeks in the LT-DBS and SHAM group. In the ST-DBS group, EEG was recorded continuously during the first 8 weeks of the experiment. Result: Development in daily seizure frequency is significantly different between LT-DBS and SHAM. Seizure frequency in the SHAM group rose from 0.1 0.1 seizures/day in week 1 to 26.6 3.1 seizures/day in week 14. This rise in seizure frequency was significantly reduced in the LT-DBS group (0.5 0.1 seizures/day in week 1 to 1.2 4.14 1 seizures/day in week 14). No differences between SHAM and ST-DBS rats were observed. Conclusion: LT-DBS initiated shortly after SE reduces the development of spontaneous seizures. These results show that temporary treatment with hippocampal DBS can affect disease progression.
p088 LENTIVIRAL VECTOR-DELIVERED SMALL INTERFERING RNA TARGETING TO HIF-1A GENE EFFECT ON MDR1B GENE EXPRESSION IN RAT ASTROCYTES MODEL INDUCED BY CORIARIA LACTONE L. Chen*, T. Zeng*, Y. Li, and D. Zhou *West China Hospital of Sichuan University, Chengdu, China; Chengdu, China; and West China Hospital, Chengdu, China
Purpose: Over-expression of multidrug resistance gene (MDR1) is an important mechanism of refractory epilepsy. Epileptic seizure may lead to accumulation of hypoxia-inducible factor-1a (HIF-1a) in hippocampus and temporal lobe. MDR1 gene-promoter contains a functional HIF-1a binding site, which is known as the classical hypoxia response element (HRE). Thus, we have the hypothesis that expression of Pgp is up regulated by HIF-1a in refractory epilepsy, which has been observed in cancer pharmacoresistance research. So the objective of this study is to explore the correlation of Pgp expression with HIF-1a in refractory epilepsy rat model. Method: We established a kindling model of MDR temporal lobe epilepsy (TLE) by intramuscular injection Sprague-Dawley rat with coriaria lactone (CL), and served normal SD rats with normal sodium (NS) injection as control group. The fragment gene carrying rat HIF-1a siRNA was cloned into lentiviral vector, identified with PCR and sequencing analysis. The correct reconstructed lentiviral vector was packaged into HEK 293 cells, then amplified and purified and injected into rat lateral cerebral ventricle. The expression level of MDR1b and its translational product P-glycoprotein (Pgp) were monitored with Real-time PCR and Western-blot analysis before lentiviral vector transfection and after (at different times). Result: The recombinanted lentiviral vectors target to rat HIF-1a were successfully constructed and packaged. It can infected the rat astrocytes with higher efficiency. For the rat model, the mRNA and protein levels of HIF-1a increased significantly (P<0.05) in hippocampus and temporal lobe, compared with control group. An accordant result was obtained in the expression of Pgp. After reconstructed lentiviral transfection, the levels of HIF-1a and Pgp decreased at the same time in the same brain region. Conclusion: Our study demonstrates that HIF-1a expression increased in accordance with Pgp in hippocampus and temporal lobe of refractory epilepsy rat model induced by CL. And the recombinant lentivirus delivered Small Interfering RNA targeting to HIF-1a gene can suppressed not only the overexpression of HIF-1a, but also the expression of MDR1b in model brain without obvious cell toxicity. So that HIF-1a may take an more important role in the mechanism of refractory epilepsy. further more, this study may provide a promising technique for refractory epilepsy remedy.
p087 SUDEP FOLLOWING STATUS EPILEPTICUS A. Lacey*, M. I. Rees, P. Smith, and R. H. Thomas* *Swansea University, Swansea, UK; Institute of Life Science, Swansea, UK; and Wales Epilepsy Research Network, Swansea, UK
Purpose: Status epilepticus (SE) is a life-threatening complication of epilepsy and a medical emergency. However, for some, an episode of SE is their first presentation of epilepsy. Method: Using the Secure Anonymised Information Linkage (SAIL) databank at we scrutinised primary care records in Wales for patients who have had an episode of SE. In order to better understand the prognosis of epilepsy following SE we looked at contemporaneous comorbidities and mortality records. Result: Since 1991 there have been 2.9/100,000 episodes of SE recorded in Wales. 732 people were identified as having SE and there were 174 deaths recorded; 15.5% were within six months of SE. In total there were 13 potential cases of SUDEP. 12.8% of people who first presented in SE (and later died) had epilepsy as a cause of death compared to 3.1% of those who had pre-existing epilepsy prior to SE (p>0.02). 2.5 times more people presenting with SE without known epilepsy were known to have a brain tumour (n=10, 3.6%). On Seven occasions more people with epilepsy had a change of medication within a month of SE (32%) than people who had SE without a prior diagnosis of epilepsy (4%; p>0.0001). Conclusion: This nationwide study identifies that SE as a first presentation of epilepsy is associated with an increased risk of SUDEP although not all cause mortality. We believe that SE occurring from pre-existing epilepsy may be triggered by poor medication concordance or change in drug regime, rather than a new symptomatic cause such as tumour or stroke.

p089 ELECTROGRAFIC SEIZURES AND PERIODIC EPILEPTIFORM DISCHARGES IN PATIENTS WITH POSTANOXIC COMA E. Altindag*, Z. V. Okudan, B. Baykan, O. Gungor Tuncer *, B. Aksay Koyuncu*, S. Tavukcu Ozkan *, and Y. Krespi* _ *Istanbul Florence Nightingale Hospital, Istanbul, Turkey; Istanbul Bilim University, Istanbul, Turkey; and Istanbul University Istanbul Medical Fakulty, Istanbul, Turkey
Purpose: We aimed to examine the predictors and prognostic value of electrographic seizures (ESZs) and periodic epileptiform discharges (PED) of post-anoxic coma patients in intensive care unit (ICU).
28 Abstracts
Method: The clinical, EEG and neuroimaging findings of consecutive anoxic comatose patients due to cardiac arrest were studied between 2009 and 2011. EEG data was reviewed by 2 investigators independently. Result: Seventeen patients (7 F; mean age: 59.816.9) were admitted to our study. The mean duration of hospitalization was 54.6 days. The outcome included death in 7 patients, severe neurological deficits in 6 patients. Thirteen patients had Glasgow Coma Score. Conclusion: MSE and various electrographic patterns detected in patients with post-anoxic coma could not predict the mortality. Larger prospective studies are warranted to determine the impact of these patterns more precisely. Method: We reviewed the data concerning the efficacy and safety of IV Lacosamide for RSE in 21 consecutive patients. Result: Patients average age was 60 [1485] years-old. Eleven patients had preexisting epilepsy. The most frequent RSE was convulsive in 70%. Seizure semiology was most likely complex partial (11) or generalized tonic-clonic (6). The RSE was classified as remote symptomatic (9), acute symptomatic (8) and cryptogenic (3). The most frequent etiology was the vascular lesion (50%). The IV Lacosamide was started with an initial bolus of 200 mg, and then followed by maintenance or individualized daily dose increases, depending on the electroclinical response. Lacosamide was used as a second drug (1), third drug (7) or fourth drug (12). Overall, RSE cessation was achieved in 55% of patients, of whom 40% within 72 hours. The highest rates of success were obtained by combining benzodiacepines, levetiracetam and Lacosamide. Four patients died during the RSE and six required further sedation. Somnolence and gastrointestinal symptoms were all the adverse events attributable to lacosamide in two patients. IV LCM was switched to equal doses per oral at hospital discharged. Five patients died remotely and 10 have remained seizure-free during the follow-up (5 months [120]). IV LCM can be an option for RSE as a previous step to sedation in the protocol of treatment of the RSE.
p090 STATUS EPILEPTICUS, A HOSPITAL BASED SYSTEMIC CASES REVIEW IN SOUTHERN TAIWAN C. Lo National Cheng Kung University Hospital, Yunlin, Taiwan
Purpose: Little are studied the systemic clinical features of status epilepticus (SE) in Southern Taiwan. To have a basic understanding of these features, including age and sex distributions, SE types, aetiologies, prognosis, anatomic correlations, validities of the investigation tools, etc; and to promote further clinical researches in SE, a systemic cases review was carried out. Method: Epilepsy cases admitted to the Chiayi Christian Hospital or the National Cheng Kung University, Douliou branch, during 20012011, were reviewed. Inclusion criteria were those who fit current SE definition suggested by the ILAE, ie continuous seizures up to 5 minutes without stopping, or no return of consciousness to the baseline between 2 or more consecutive seizures. Exclusion criteria were those with incomplete medical records or poor evidence in suggesting SE. Result: Altogether 173 patients entered the systemic cases review. Male to female ratio was 103:73 (59.5% vs 40.5%). Most patients were in their seventies [40/173 (23.1%)] and sixties [37/173 (21.4%)]. 145 patients had convulsive SE, and 28 had non-convulsive SE. The leading causes in SE were cerebral vascular disease [59/173 (34.10%)], metabolic disorders [48/173 (27.7%)], and poor seizures control [43/173 (24.8%)]. Frontal and temporal lobe lesions were the leading damages seen in images. Epileptiform discharges did not always correlate the lesions found in images. Conclusion: Several issues raised that need further study, including the discrepancy in sex distribution; the correlation between EEG and images findings, the mechanism causing higher risks in having SE with frontaltemporal lesions, and the impact of co-morbidities in causing SE in the elderly.
p092 SELECTIVE LENTIVIRAL MEDIATED TARGETING OF GLIA CELLS IN THE CENTRAL NERVOUS SYSTEM M. Fassler, I. Weissberg, N. Levi, A. Monsonego, R. Taube, and A. Friedman Ben-Gurion University of the Negev, Beer Sheva, Israel
Purpose: In a complex tissue of the central nervous system (CNS), cell cross-talk is essential to preserve normal functions. Current tools for dissecting the molecular mechanisms that mediate cell-cell interactions within the brain are technically challenging, time consuming and difficult to control. In this study we report the establishment and validation of a lentiviral-mediated gene-targeting platform to specific cells in the CNS. Method: Using lentiviral-mediated gene-targeting platform that combines unique features of self-inactivated lentiviruses that promote stable gene delivery into non-dividing cells and efficient display of single-chain variable region human fragments (scFv) or soluble IgG on the surface of viral particles. Result: In vitro, cells that express the receptor-binding domain of the SARS-CoV spike glycoprotein were targeted by engineered sindbis pseudotyped lentiviruses that incorporate specific scFvFc attachment moieties. Additionally, in vitro targeted gene expression to primary astrocytes was also demonstrated, using engineered lentiviruses that incorporate Aquaporin 4 and GLAST IgG. In vivo, lentiviral targeting of astrocytes and oligodentrocytes progenitor cells that express the chondroitin sulfate proteoglycan, NG2 was obtained using viral particles that display an anti-GLAST and anti-NG2 IgG antibodies, repectively. Conclusion: We conclude, that this novel approach will be implemented in the model of epilepsy to study the role of astrocytes in the pathogenesis of the disease and challenge its use as a therapeutic tool.
p091 IV LACOSAMIDE AS THERAPEUTIC OPTION FOR REFRACTORY STATUS EPILEPTICUS BEFORE COMA INDUCTION E. Santamarina, M. Toledo, M. Sueiras, M. Raspall, N. Allouti, E. Lainez, M. Vicente, J. Conill, M. Roig, and X. Salas-Puig Vall dHebron University Hospital, Barcelona, Spain
Purpose: Refractory status epilepticus (RSE) is a neurological condition that often requires sedation to be controlled. IV Lacosamide is a novel antiepileptic drug that may provide some benefits in RSE before inducing coma.
p093 ASYMMETRIES OF SLEEP SPINDLES IN HUMAN EPILEPSY WITH TEMPORAL OR FRONTOTEMPORAL FOCUS A. Kyrozis, C. Moschovos, E. Tsoukas, A. Bonakis, D. Pandis, A. Ghika, I. Evdokimidis, and N. Kalfakis Univ. Athens, Athens, Greece
29 Abstracts
Purpose: It is unclear whether temporal lobe epileptic foci can affect sleep spindles, which are generated in extratemporal thalamo-cortical circuits. We tested for such effects, the detection of which may have pathophysiologic and clinical diagnostic implications. Method: Sleep EEG recordings of 6 cryptogenic epilepsy patients with right temporal or frontotemporal focus (TR), 6 with left temporal or frontotemporal focus (TL) and 12 controls with non-epileptic paroxysmal events and normal MRIs were used. Central sleep spindles were detected by a custom-made computer algorithm (MATLAB software). Spectral power, peak frequency, inter-channel transfer function estimate (TFE) angle (reflecting phase difference) and inter-channel coherence were assessed. Result: No significant inter-hemispheric differences were found for peak frequency and spectral power. Spindles recorded at frontal electrodes appeared a few milliseconds earlier on the side of the focus in 11 of 12 epilepsy cases. The lateralization was highly significant (meanSEM TFE angles from F3 to F4: TR: + 0.2120.055; TL: - 0.2040.077, Tukey test p=0.0057). Coherence was also higher on the side of the epileptic focus [Coh (F3Fz)Coh (F4Fz): TR: -0.0550.06; TL: +0.090.025, Tukey test p=0.028], implying greater synchronization on the side of the focus. Conclusion: Temporal lobe epilepsy promotes initiation and synchronization of sleep spindles on the side of the focus. The observed changes may be the result of network modifications on the side of the focus and/or altered hippocampal-frontal networks that modulate sleep oscillations. The results suggest the possibility of using sleep spindles for the detection of the presence and side of an occult epileptic focus. adenosine into the ictal focus is likely to be effective in the control of intractable seizures.
p095 ALPHA-LACTOALBUMIN, A WHEY PROTEIN RICH IN TRYPTOPHAN, IS EFFECTIVE IN RODENT MODELS OF SEIZURES AND EPILEPTOGENESIS G. De Sarro*, F. Scicchitano*, R. Citraro*, S. Chimirri*, P. Mainardi, E. Perucca, and E. Russo* *University of Catanzaro, Catanzaro, Italy; University of Genova, Genova, Italy; and Pavia, Italy
Purpose: ALAC (alpha-lactoalbumin), a whey protein rich in tryptophan, shows protective activity in preclinical models of seizures and epilepsy and was recently associated with improved seizure control in patients with drug-refractory epilepsy.1,2 We evaluated the potential activity of ALAC in some other rodent models of seizures and epileptogenesis and we explored a possible mechanism of action. Method: The effects of ALAC (oral administration) were tested in two standard epileptogenesis protocols, namely the pilocarpine post-status epilepticus model in mice and the WAG/Rij rat model of absence epileptogenesis.2,3 The mechanism of action was investigated by assessing the effects of ALAC in two seizure models (NMDA and PTZ-induced seizures) including D-serine co-administration4. Result: ALAC showed protecting properties in both models of epileptogenesis, reducing spontaneous seizures development. In acute seizure models, ALAC possessed antiseizure properties at some of the doses tested (PTZ-seizures: 50% seizure-reduction at 250mg/kg; NMDA-seizures: 90% reduction at 250 and 500mg/kg). When a dose of D-Serine ineffective per se was co-administered with ALAC, ALAC effects were significantly reversed in both models. Conclusion: ALAC is active in experimental models of seizures and epileptogenesis. Its effects are likely mediated by the inhibition of NMDA receptors at the glycine binding site, possibly secondarily to the in-vivo enzymatic conversion of ALAC-generated tryptophan to kynurenic acid. However, other mechanisms of action contributing to ALAC effects cannot be excluded. References: 1 Mainardi, et al., 2008. Med Hypotheses 70, 8769. 2 Citraro et al., 2011 Epilepsy Res 95, 609. 3 Russo et al., 2011 Epilepsia 52, 134150. 4 Russo et al., 2004 Neuropharmacology 46:86578.
p094 WIRELESS INSTANTANEOUS ADENOSINE RECORDING DURING KAINIC ACID-INDUCED SEIZURE IN RAT: WINCS APPLICATION Y. Shon*, and S. Lim *Yeouido St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea; and St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea
Purpose: Adenosine, as the brain's endogenous anticonvulsant, is considered to be responsible for seizure arrest and postictal refractoriness. We performed ictal EEG & co-monitoring of neurotransmitter recording by WINICS (wireless instantaneous neurotransmitter concentration system, fast-scan cyclic voltammetry based) in the acute hippocampal seizure model of rat. Method: Rats (n=18) were implanted with bipolar hippocampal depth electrodes and a cannula for the injection of KA (1 mcg/4min) in the right hippocampus (CA3) under urethane anesthesia. WINCS recording electrode was inserted in left hippocampus (mirror site of R HC). Simultaneous recordings of EEG (8 channels) and WINCS were performed continuously after KA induced limbic status epilepticus (usually 10 15min after injection). Result: There were two patterns of adenosine release during the KA induced limbic status epilepticus. First, intermittent and phasic release of adenosine (n=2) was clearly observed only during the early period of slow, large-amplitude spike and wave, but not at the low-amplitude fast or repetitive spikes among the recurrent ictal EEG pattern. Second, there were a rapid adenosine and dopamine release immediately at the time point of sudden, transient disappearance of polyspike or spike-wave discharges in the EEG (n=7). Conclusion: Our study shows that the slow phase of spike-wave complex or its transient disappearance after prolonged status epilepticus may be linked to a suppression of neuronal hyperexcitability via adenosine release. We may suppose that the local delivery of
p096 THECX32 GENE EXPRESSION IN BRAIN FOCI OF PATIENTS WITH REFRACTORY EPILEPSY W. Lin, and L. Zhang the first hospital of Jilin University, 130021, China
Purpose: In order to study CX32 gap junction gene expression in the brain epileptic foci of patients with refractory epilepsy, and lay the foundation for clinical research and treatment of refractory epilepsy. Method: 24 patients with refractory epilepsy that have undergone surgery in the experimental group, 10 patients with traumatic brain injury that have undergone emergency surgery in control group. epileptic brain foci tissue were removed from surgery, immunohistochemistry and immune electron microscopy methods were used to observe CX32 expression in both group. Result: Immunohistochemistry results showed that CX32 expression in the experimental group was higher than the control group (p<0.001), There are more colloidal gold particles labelling CX32 on the membranes
30 Abstracts
of nerve cells in the brain tissue of the experimental group than the control group under electron microscopy (p<0.001). Conclusion: The expression of CX32 in the epileptic brain foci was increased, which may play an important role in the happen and development of epilepsy.
Epilepsy Surgery 1 Monday, 01 October 2012

p099 LATERALIZATION AND LOCALIZATION OF POSTTRAUMATIC EPILEPSY WITH DUAL PATHOLOGY USING FORAMEN OVALE ELECTRODES: A CASE REPORT H. Henninger*, D. T. Hsieh, E. N. Eskandar, and A. J. Cole *Maine Medical Partners Neurology, Scarborough, USA; Massachusetts General Hospital, Boston, USA; and MGH Epilepsy Service, Massachusetts General Hospital, Boston, USA
Purpose: Traumatic brain injury is typically multifocal and may consist of bleeding, gliosis, axonal injury, and hippocampal sclerosis. Each of these mechanisms may lead to post-traumatic epilepsy. When more than one possible seizure onset zone is present concomitantly, this is often referred to as dual or multifocal pathology. Foramen ovale electrodes can lateralize and localize mesial temporal lobe epilepsy in cases where clinical uncertainty exists. Method: A 57-year-old left handed man was evaluated for medically refractory epilepsy. Epilepsy began at age 19 following a motorcycle accident resulting in a left temporal intraparenchymal hemorrhage. MRI demonstrated marked left temporoparietal encephalomalacia as well as right hippocampal atrophy with increased T2 signal intensity. Surface EEG captured several right temporal lobe seizures, however concern about the role of the left hemisphere lesion led to prior rejection of resective epilepsy surgery. Results: Bilateral foramen ovale (FO) electrodes were surgically placed for continuous EEG recording. Six electro-clinical seizures were recorded with clear onset in the right FO electrodes. Right anterior temporal lobectomy was performed resulting in seizure freedom with minimal effect on memory. Conclusion: Post-traumatic epilepsy with dual or multifocal pathology can present a clinical dilemma, especially if the site of apparent seizure onset is contralateral to the most extensive post-traumatic injury. When mesial temporal seizure onset is suspected, foramen ovale electrode EEG monitoring can provide confirmation of lateralization and localization of the seizure onset zone without further invasive monitoring.
p097 GABAERGIC EXCITATORY MECHANISMS ARE INVOLVED IN THE GENESIS OF EPILEPTIC ACTIVITIES IN THE CORTEX SURROUNDING GLIOMA IN HUMANS G. Huberfeld*, J. Pallud*, M. Levanquyen, M. Baulac, F. Bielle, C. Duyckaerts, F. Roux, R. Miles*, and L. Capelle *CRICM - UPMC - INSERM - CNRS, Paris, France; Hpital de la Piti-Salptrire, Paris, France; CHU Pitie-Salpetriere, Paris, France; and CH Ste Anne, Paris, France; and
Purpose: Brain gliomas are associated with seizures in a majority of patients, but their pathophysiology and link with the tumor is still unclear. Method: The physiology of the resected tumor and surrounding security margin can be explored in neocortical slices providing a novel opportunity to explore epileptogenic mechanisms in human tissue. Result: We found that postoperative glioma tissues of 69% patients spontaneously generated interictal-like discharges. These events were synchronized in superficial layers of cortical columns in the neocortex surrounding glioma areas that presented a tumor infiltration. They were never recorded in the tumor core or in control tissues. Interictal-like events depended on both depolarizing GABAergic and glutamatergic transmission. Interneuron firing preceded them, and Chloride homeostasis was perturbed in 65% of pyramidal cells resulting in a depolarization induced by GABA. Ictal-like activities could be exclusively generated in these areas. They were preceded by a long range period characterized by the progressive emergence of glutamatergic preictal discharges. Conclusion: These epileptic activities sustained by excitatory effects of GABA, as those reported in human temporal lobe epilepsies, suggest that cellular Chloride regulation processes affecting oncogenesis are involved in the excitatory/inhibitory imbalance causing epileptic activity in peritumoral tissue.
p098 THE OUTCOME OF ANTIEPILEPTIC DRUG THERAPY IN BENZODIAZEPINE-RESISTANT STATUS EPILEPTICUS: A REVIEW OF PUBLISHED CASES AND TRIALS Z. S. Y. Yasiry UCL Institute of Neurology, London, UK
Purpose: This work addresses the question of what drug(s) is(are) the next most effective when benzodiazepines fail to control convulsive status epilepticus. Method: A systematic search of literature for the outcome of the use of phenobarbital, phenytoin, valproate, levetiracetam and lacosamide has been carried out. Result: Ninety eight papers have been included in the review. The evidence base is categorized as level 111, and the use of each drug has advantages and disadvantages. Conclusion: The paper presents a detailed analysis of the published papers and a comparison of these widely-used drug therapies.
p100 A PROSPECTIVE LONG-TERM STUDY ON THE OUTCOME AFTER VAGUS NERVE STIMULATION AT MAXIMALLY TOLERATED CURRENT INTENSITY IN A COHORT OF CHILDREN WITH REFRACTORY SECONDARY GENERALIZED EPILEPSY A. Cukiert*, C. Cukiert*, A. Lima*, J. Burattini*, C. Forster*, C. Baise, and M. Argentoni-Baldochi *Clinica De Epilepsia De Sao Paulo, Sao Paulo, Brazil; and Hospital Brigadeiro, So Paulo, Brazil
Purpose: We report the outcome after VNS in kids with secondary generalized epilepsy, and advance in the discussion of issues rarely addressed such as maximal stimuli intensity, seizure worsening, honeymoon effect, and specific seizure type control rates. Method: Twenty-four consecutive children with Lennox-Gastaut or Lennox-like syndrome under the age of 12 years by the time of surgery, were prospectively included in the study. The generator was turned on using 0.25mA, 30Hz, 500lsec, 30sec on, 5 minutes off stimuli parameters; current was then increased by 0.25mA every 2 weeks, until 3.5mA was reached or adverse effects were noted.
31 Abstracts
Result: Six kids got an end-of-study (24 months) post-implantation video-EEG and their findings were similar to those before vagus nerve stimulation. Quality of life and health measures improved in up to 50% (mean=25%) in 20 kids. Attention was noted to improve in 21 out of the 24 kids. Final intensity parameters ranged from 2 to 3.5mA (mean=3.1mA). An at least 50% seizure frequency reduction immediately after implantation and with the generator off was noted in 14 out of the 24 kids. There were 47 seizures types among the 24 children. An at least 50% seizure frequency reduction was noted in 35 seizure types and 17 seizures types disappeared after VNS. Atypical absence, myoclonic and generalized tonic-clonic seizures were significantly reduced by VNS; tonic and atonic seizures did not improve. Transient seizure frequency worsening was noted in 10 of the 24 kids, at a mean of 3.1mA. Conclusion: Our study showed that VNS was effective in reducing atypical absence, generalized tonic-clonic and myoclonic seizures (but not atonic or tonic seizures) in kids with Lennox-Gastaut or Lennox-like syndrome. A concomitant improvement in attention level and quality of life and health was also noted. Secondary generalized epilepsy might represent a subset of good candidates for VNS. it is still an unresolved question at which age surgery should best be performed. In light of decreasing plasticity and the cumulative impact of seizures and anticonvulsants on neurodevelopment, early surgery appears preferable. This study aimed to determine whether early hemispherectomy leads to better long-term outcome than surgery at an older age. Method: We retrospectively investigated the medical, cognitive-behavioral and psychosocial long-term outcome (follow-up: 9.4yrs [1.119.4]) of hemispherectomy as a function of age at surgery (early: <7yrs/intermediate: 716yrs/late: >16yrs) based on a structured postal questionnaire in a large patient sample (N=61/81, return rate: 75%). Result: Best seizure outcome was obtained for early surgery patients (90% seizure free). Patients with late surgery, however, had higher pre- and postsurgical intelligence and achieved better psychosocial outcome. Surgery at an intermediate age yielded cognitive-behavioral improvements most often. Binary logistic regression confirmed higher age at surgery and higher presurgical intelligence as positive predictors of postsurgical intelligence; lower presurgical intelligence and postsurgical seizure freedom predicted intellectual pre-post improvements. Conclusion: Contrary to expectations, we found no evidence for advantages of early surgeries regarding postsurgical cognition and achievement. These data do not suggest to postpone surgery but higher age should not exclude patients from hemispherectomy. Presurgical intelligence serves as indicator of the severity of the disease and the functional integrity of the contralateral hemisphere, which determine cognition and eventually psychosocial outcome. Postsurgical improvements are possible, particularly in case of seizure freedom.
p101 THE EFFICACY OF VNS IN PHARMACORESISTANT EPILEPSY OF TEMPORAL VERSUS EXTRA-TEMPORAL LOBE LOCATIONS A. Abubakr*, and I. Wambacq *University of Mississippi Medical Center, Jackson, USA; and Montclair State University, Bloomfield, NJ, USA
Purpose: This is a retrospective study evaluating the effectiveness of VNS therapy in patients with refractory epilepsy of temporal versus extra-temporal lobe locations. Method: The medical records of 31 patients implanted with VNS between1998 and 2001 were reviewed. Patients were divided into TLE group and extra TLE group based on the epileptogenic foci. Changes in seizures frequency was assessed at one year following VNS implant. Patients with >50% reduction in seizures frequency were considered responders to VNS therapy. Result: Out of 31 patients one died of unrelated cause, and another asked their device to be removed due adverse effects. There were 9 patients with TLE (5 males and 4 females), age range 2761 yrs, with epilepsy duration of 440 yrs, and seizures frequency of 1450/month and taking an average 25 AEDs a day. There were twenty patients with extra TLE (9 males and 11 females), age range 1462 yrs, epilepsy duration of 854 yrs, and seizures frequency of 3900/month and taking 24 AEDs a day. Six out of 9 with TLE (66%) and 11 out of 20 with extra TLE (55%) were considered responders to VNS therapy (>50% reductions in seizure frequency) at one year following the implant. There was no significant difference between the two groups (P = 0.88). Conclusion: This observation demonstrates that VNS is an effective therapy in patients with either TLE or extra TLE focus and there is no difference in the responder rate between various epileptogenic foci.
p103 CHILDHOOD TEMPORAL LOBE EPILEPSY: BEYOND HIPPOCAMPAL SCLEROSIS A. Mhlebner-Fahrngruber, M. Schmook, D. Prayer, A. Dressler, G. Kasprian, G. Grppel, G. Pahs, T. Czech, and M. Feucht Medical University Vienna, Vienna, Austria
Purpose: Herein, we focused on clinico-pathological variants of childhood drug-resistant temporal lobe epilepsy (TLE): pre- and postsurgical data of 17 patients (14 female; 9 left TLE), who underwent epilepsy surgery, were reviewed. Method: Video-EEG monitoring including sphenoidal electrodes was analyzed with regard to clinical lateralizing signs defining the clinical symptomatogenic, the seizure onset and the irritative zon. MRI was reviewed with respect to presence of hippocampalsclerosis, small temporal lobe, blurring of the grey-white matter junction, signal changes of the subcortical white matter, and thickening of the adjacent cortex. Histopathology was routinely processed for histopathology. Result: Six children had anterior temporo-polar resection. All six children displayed additional FCD IIIa. All six patients had a history of febrile seizures. In 5/6 the typical MRI changes in temporal lobe were found. All six of them were seizure free after surgery. Five children who underwent anterior temporo-polar resection showed HS without FCD IIIa. 2/5 had febrile seizures. Only 1/5 displayed the typical MRI changes. Outcome was Wieser 1a in 2 children, Wieser 2 was found in 1 and Wieser 3 in 2 patients. Six patients underwent selective amygdalohippocampectomy and therefore temporal cortex was not available. 4/6 had febrile seizures. None of them had changes in the temporal lobe on MRI scan. 5 were seizure free after surgery, 1 had outcome Wieser 3. Conclusion: In summary, the combination of certain clinical characteristics, clear-cut signal alterations on MRI scan, sufficient surgical resection as well as certain histopathological diagnosis is associated with a favourable outcome in childhood temporal lobe epilepsy.
p102 HEMISPHERECTOMY AN OPTION ALSO FOR ADOLESCENT AND ADULT PATIENTS A. Althausen*, U. Gleissner, C. Hoppe*, R. Sassen*, S. Buddewig*, M. Von Lehe*, J. Schramm*, C. Elger*, and C. Helmstaedter* *University of Bonn, Bonn, Germany; and LVR-Klinik Bonn, Bonn, Germany
Purpose: Hemispheric neurosurgery is an established treatment for severe epilepsy caused by extended unilateral brain pathology. However,
32 Abstracts
p104 CENTROMEDIAN THALAMIC DEEP BRAIN STIMULATION FOR THE TREATMENT OF REFRACTORY GENERALISED AND FRONTAL EPILEPSY: A BLINDED CONTROLLED STUDY A. Valentin*, R. Chelvarajah, R. Selway, L. Vico*, R. Garca De Sola, E. Garcia Navarrete, and G. Alarcon* *King's College London - Institute of Psychiatry, London, UK; King's College Hospital, London, UK; and Hospital Universitario de la Princesa, Madrid, Spain
Purpose: Deep Brain Stimulation (DBS) of the thalamus is an emerging surgical option for medically refractory epilepsy sufferers who are not suitable for resective surgery, or where surgery has failed. In a singleblind within-subject control study, we evaluate the efficacy of DBS of centromedian nucleus (CMN) for seizure control as well as quality-of-life outcome in symptomatic generalised epilepsy (SGE), and frontal lobe epilepsy (FLE). Method: Eleven patients were recruited (8 males, 3 females) at King's College Hospital (London, UK) and Hospital de la Princesa (Madrid, Spain). Six patients had removal of the VNS device before DBS implantation. Ages at surgery range from 18 to 51 years (mean 37). Average follow-up period is 2 years. Six patients had SGE and five FLE. Seizure diaries were kept by patients/parents prospectively. Patient reported outcome measures (PROMs) were completed at regular time-points. Result: Among the 6 patients with SGE, 2 patients became seizure free for more than 4 years, 3 had seizure frequency reduction greater than 50% and one had seizure reduction of 37.5%. None of the patients with FLE became seizure free, 2 had a reduction greater than 50% and 2 showed no change. PRO questionnaires showed improvement in approximately 50% of patients. Conclusion: DBS of CMN appears to be effective in improving seizure control and patient related outcomes in patients with generalised epilepsy and possibly in frontal lobe epilepsy. two. Seizures originated from the temporal lobe in ten patients, from the temporo-parieto-occipital region in one, and were bitemporal in one. At 1 year follow-up eight patients were seizure free, one had worthwhile improvement and the remaining three had experienced no benefit. Postoperative outcome was available in ten patients at 2 years and in three at 5 years, and remained stable in all but one. The most frequent underlying pathology was dysembryoplastic neuroepithelial tumor (DNET). Conclusion: Epilepsy surgery can be performed effectively in patients with NF1 and drug-resistant seizures. In spite of the frequently multifocal nature of the disorder, a single and well-delimited epileptogenic zone can be recognized. The high prevalence of DNETs in this series might suggest that association of this developmental tumor with NF1 is not fortuitous.
p106 LONG-TERM OUTCOME AFTER CALLOSOTOMY OR VAGUS NERVE STIMULATION (VNS) IN CONSECUTIVE PROSPECTIVE COHORTS OF PATIENTS WITH SECONDARY GENERALIZED EPILEPSY C. Cukiert, A. Cukiert, J. Burattini, and A. Lima Clinica De Epilepsia De Sao Paulo, Sao Paulo, Brazil
Purpose: Palliative procedures such as callosotomy or VNS have been used for treatment of refractory secondary generalized epilepsy. We compared the outcome from these palliative procedures in two consecutive prospective cohorts of patients with secondary generalized epilepsy. Method: Twenty consecutive patients with refractory secondary generalized epilepsy submitted to callosotomy (Group 1) and additional 20 patients submitted to VNS were studied (Group 2). Patients with specific etiology (cortical dysplasia, tuberous sclerosis etc) were excluded from the study. Result: MRI showed atrophy in 70% of Group 1 and in 65% of Group 2 patients; non-specific gliosis was present in the remaining patients. All patients had multiple seizure types. Both procedures were similarly effective regarding the control of atypical absences and generalized tonic-clonic seizures, and both were not effective in controlling tonic seizures. Callosotomy was very effective in reducing atonic seizure's frequency, while VNS was ineffective. On the other hand, callosotomy was not effective in reducing myoclonic seizures, while VNS did so. Rupture of secondary bilateral synchrony was noted in 85% of Group 1 patients; there was no EEG modification after VNS in group 2. Attention improvement was equally noticed in both Groups. All but one Group 1 patients disclosed an acute callosal disconnection syndrome immediately postoperatively, lasting for up to 3 weeks. Longer hospital stays (including ICU) and blood transfusion were characteristics of Group 1 patients only. Conclusion: Both procedures were effective in treating patients with refractory secondary generalized epilepsy. Specific seizure types responded differently to each treatment.
p105 EPILEPSY SURGERY IN NEUROFIBROMATOSIS TYPE 1 C. Barba*, T. Jacques, P. Kahane, T. Polster, J. Isnard, F. S. S. Leijten**, C. zkara, L. Tassi, F. Giordano*, M. Castagna, A. John, B. Oz, N. Streichenberger, C. Salon, R. Guerrini*, and H. Cross*** *Children's Hospital Meyer, Florence, Italy; Great Ormond Street Hospital NHS Trust, London, UK; Grenoble University Hospital, Grenoble, France; Bethel Epilepsy Centre, Bielefeld, Germany; Hpital Neurologique, Lyon, France; **Rudolf Magnus Institute of Neuroscience, UMC Utrecht, Utrecht, The Netherlands; Istanbul University School of Medicine, Istanbul, Turkey; Niguarda General Hospital, Milan, Italy; University of Pisa, Pisa, Italy; Cerrahpasa Medical School, Istanbul, Turkey; and ***ILAE Commission Of Paediatrics, London, UK
Purpose: To report on 12 patients with Neurofibromatosis type 1 (NF1) and drug-resistant seizures, who underwent epilepsy surgery and describe their clinical presentation, outcome and histopathology. Method: We included in the study patients with NF1 who had undergone surgery for drug-resistant epilepsy and had at least one year postoperative follow-up. Result: We collected 12 patients from eight European epilepsy centers. MRI abnormalities were detected in all patients but one and were unilateral temporal in eight, bilateral in one and multilobar or hemispheric in
p107 BELGRADE EPILEPSY SURGERY PROGRAM: EARLY OUTCOME OF THE FIRST 35 OPERATED PATIENTS D. V. Sokic*, V. L. Bascarevic, A. J. Ristic*, N. M. Vojvodic*, A. Parojcic, S. Lavrnic, L. Brajkovic, M. M. Kovacevic, S. M. Jankovic, and B. Djurovic *Clinic of Neurology Clinical Center of Serbia, University of Belgrade School of Medicine, Belgrade, Serbia; Clinic of Neurosurgery, Clinical Center of Serbia, University of Belgrade, School of Medicine, Belgrade, Serbia; Clinic of Neurology, Clinical Center of Serbia, Belgrade, Serbia; Center for Magnetic Resonance, Clinical Center of Serbia, Belgrade, Serbia; and Institute of Nuclear Medicine, Belgrade, Serbia
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Purpose: Although approximately 200 patients underwent surgery for medically intractable epilepsy between 1975 and 1995 in Belgrade, epilepsy surgery program was temporarily interrupted for almost 15 years. Contemporary Belgrade Epilepsy Surgical Program was restarted in 2006. Method: Noninvasive presurgical evaluation was performed in 281 pharmacoresistant epilepsy patients and included 510 days video-EEG telemetry, 1.5 T MRI with appropriate angulation, and neuropsychological testing in all, and interictal PET and/or interictal/ictal SPECT in 19% of patients. Indication for operation was established if the acquired data showed high concordance. Result: Surgery was performed in 35 (12%) patients: left side anterior temporal lobectomy with amigdalo-hippocampectomy in 21 (60%), and right side in 13 (37%) patients. Lesionectomy in right frontal lobe was performed in 1 patient. Histology showed hippocampal sclerosis in 22, dual pathology in 5, focal cortical dysplasia in 4, glioma in 2, DNET in 1 and cavernoma in 1 patient. Perioperative complications occurred in 10 (28%) patients and included dysphasia and dyslexia without permanent radiological infarction (4), hemiparesis (2), infection (3), and amnesia (1). All complications (except hemiparesis due to brain infarction in 2 patients) were transitory. Four patients had GTC seizures after surgery and in 2 of them seizures continued to occur. Seizure remission was obtained in 33 (94%) patients during 3 to 65 (median: 11) months of follow-up. New onset psychosis (3), depression (1) and anxiety (1) occurred after surgery but responded to appropriate therapy. Conclusion: Early surgical outcome in patients with pharmacoresistant, predominantly temporal lobe epilepsy is favorable. Complications are reasonably rare. resective surgery or failures of the same. There seems to be a tendency of an increased infection rate with the number of stimulator replacements. This would stress the importance of longer battery life times or the need for rechargeable devices.
p109 LENNOX-GASTAUT SYNDROME AND CALLOSOTOMYA IN ADULTHOOD M. Herbas Rocha*, J. D. D. Del Castillo Calcneo, M. AlonsoVanegas*, D. San Juan Orta, and B. A. Sandoval Bonilla *Instituto Nacional de Neurologa y Neurociruga Manuel Velasco Suarez, Mexico city, Mexico; Angeles Pedregal Hospital, Mexico City, Mexico; National Institute of Neurology and Neurosurgery, Mexico City, Mexico; and Instituto Mexicano de Seguro Social, Mexico City, Mexico
Purpose: The Lennox-Gastaut syndrome (LGS) is one of the most severe epileptic encephalopathies of childhood that extends into adulthood. We show the sociodemographic characteristics and surgical outcome of callosotomy in adults with SLG. Method: Adults with epilepsy were identified SLG of either sex undergoing open callosotomy through the Priority Program Epilepsy and the Neurosurgery Department at National Institute of Neurology and Neurosurgery from January 2003 to October 2011. Result: A total of 21 adult patients with LGS submitted to callosotomy, 7 women (33%) and 14 males (67%), mean age 25 7 years (range 14 to 39 years), with a mean age at the time of onset of their illness than 4 years (range 3 months to 11 years) and mean duration of epilepsy of 23 years (range 11 to 38 years). The seizures most frequently found in patients were: 66.6% atypical absence (14), tonic 57.7% (12), atonic 52.3% (11), complex partial seizures 42.8% (9). All patients underwent 2/3 anterior callosotomy. The prognosis at 12 months was; 3 patients were in class A (14.2%), 12 patients in class B (57.14%), 4 class C patients (19%) and 2 in Class D (9.5%). Conclusion: Surgical callosotomy of the anterior 2/3 in adults with LGS is a safe and effective procedure for control of seizures, especially drop attacks and generalized tonic-clinic seizures. Severe mental retardation does not affect the clinical outcome and should not be considered a contraindication. Structural brain abnormalities didnt show any effect on the outcome.
Epilepsy Surgery 2 Monday, 01 October 2012

p108 SURGICAL AND HARDWARE COMPLICATIONS TO VAGAL NERVE STIMULATION FOR DRUG RESISTANT EPILEPSY. A LONGITUDINAL SINGLE CENTRE STUDY OF 143 PATIENTS H. Kahlow, and M. Olivecrona University Hospital Umea, Umea, Sweden
Purpose: To longitudinally study surgical and hardware complications to vagal nerve stimulation (VNS) treatment in patients with drug resistant epilepsy. Method: In a longitudinally retrospective study we analyzed medical records of 143 patients (81 men and 62 women) whom between 1994 and 2010 underwent implantation of VNS-device for drug-resistant epilepsy. The mean follow up time was 62 46 months, the total number of patient years was 738. Result: 251 procedures were performed in 143 patients (76 stimulator replacements). 24 patients (16.8%) were afflicted by complications related to surgery and 24 patients (16.8%) suffered from technical malfunctions. Surgical complications were: superficial infection in 5 patients, deep infection needing explantation in 5, vocal cord palsy in 8, which persisted in at least 1 patient over one year and other complications in 8. Hardware related complications were: lead wire fracture in 17, disconnection in 4, spontaneous turn-off in 2 and stimulator malfunction in 2. A tendency though, not statistically significant, was that the frequency of infections around the stimulator seemed to increase with the number of stimulator replacements. Conclusion: The complication rate and the severity of the complications to VNS surgery are in an acceptable range. VNS can safely be used as an ad on therapy in patients with drug resistant epilepsy not suitable for
p110 POSTOPERATIVE RESOLUTION OF HYPOTHALAMIC HAMARTOMA IN A PATIENT WITH GENERALIZED EPILEPSY N. Cengiz, A. Dagcnar, and K. Akpnar Ondokuz Mays niversitesi, Samsun, Turkey
Purpose: A 23-year-old rihgt handed man with typical features of LennoxGastaut syndrome and epilepsy due to hypothalamic hamartoma underwent successful endoscopic resection with seizure freedom. Ha had history of epileptic seizures since 6 years of age. Method: The diagnosis of a hypothalamic hamartoma had been made by magnetic resonance imaging (MRI) of brain . He had received previous gamma knife therapy of the hypothalamic hamartoma at 22 years of age, which did not help his seizures. At the time of presentation for surgery, he was having multiple daily seizures, including gelastic seizures, atonic seizures and generalized tonic-clonic seizures. He had failed 4 antiepileptic drugs previously. Result: His electroencephalogram showed slow generalized spike-andwave discharges at 12- hertz as well as multifocal epileptiform discharges and abnormal slow background, consistent with and typical for LennoxGastaut syndrome . Ictal - photon emission computed tomogEpilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x
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raphy performed during typical gelastic seizures demonstrated hypermetabolism in the hamartomas, hypothalamic region without cortical or cerebellar hypermetabolism . Conclusion: The patient underwent resective surgery and has been free of seizures. (8 months follow-up). After operation his EEG was normal. lobe), located 34.9% right and 65.1% left hemisphere; and 7.4% with multiple cavernous malformations (3% only extratemporal and 4.4% temporal and extratemporal), 20% located on the right, 20% left and 60% both hemispheres. Surgical outcome: Engel I 88.2%, Engel II 7.3%. Engel III 4.4%. Seizure frequency pre and post OP showed a statistical significance (p < 0.05). Mean follow up was 40.3 months. Morbilities: 4.4% quadrantanopsia, infection 1.5% and 0% mortality. Conclusion: Complete surgical resection, included lesionectomy plus corticectomy guided by electrocorticography demonstrates significant beneficial results with total seizure control in the majority of cases. Electrical activity could be associated with dual pathology (cavernous malformation plus cortical dysplasia).
p111 VAGUS NERVE STIMULATION FOR MEDICALLY REFRACTORY EPILEPSY: OUR EXPERIENCE IN A TERTIARY EPILEPSY CENTER AT THE UNIVERSITY OF SEVILLE P. M. Martinez*, M. Caballero*, C. M. Quesada*, R. Vazquez*, M. Oliver, Y. Chocron, and M. D. Jimenez* *University Hospital Virgen del Rocio, Sevilla, Spain; and Hospital Virgen del Rocio, Seville, Spain
Purpose: To evaluate long term outcomes in patients treated with vagus nerve stimulation (VNS). Method: Our experience with VNS at the University Hospital Virgen del Rocio is comprised of 6 patients with a mean age of 23.8 years and a mean duration of epilepsy of 10 years. These patients have been diagnosed with cryptogenic epilepsy (2 patients), epileptic encephalopathy secondary to perinatal anoxia (3 patients) and hemiconvulsion-hemiplegia-epilepsy syndrome (1 patient). All patients underwent a comprehensive presurgical evaluation and were found to be unsuitable candidates for resective epilepsy surgery. Mean post-implantation follow-up is 31 months. Efficacy of treatment in terms of reduction in number of seizures and referred side effects was assessed after the implantation of a VNS. Result: A greater than 50% reduction in seizure frequency (66%) was achieved. Two of the patients (34%) did not experience any improvement after VNS implantation. One patient (17%) had the device removed after experiencing hoarseness of voice. After implantation, the average number of hospital admission/ER visits days was significantly decreased. Conclusion: VNS is an effective and relatively safe adjunctive therapy for patients with medically refractory epilepsy not amenable to resection.
p113 PRE- AND POST-OP ACTIVATION OF THE MOTOR CORTEX IN EPILEPSY WITH HEMIPARESIS AND ROLANDIC ISCHEMIA R. F. Severino, D. Crestani, A. Palmini, J. Rubio Hoefel, E. Paglioli, R. Nunes, and J. Costa Da Costa So Lucas Hospital, Porto Alegre, Brazil
Purpose: We want to study the role of the primary motor cortex (PMC) in patients with vascular destructive lesions in perirolandic regions. Neuroplastic mechanisms operate and these patients have some motor functionality. This picture is more complex when occur seizures arousing from the scar and these area is resected. We report pre-and post-operative motor functional magnetic resonance (fMRI) findings in 12 patients with refractory epilepsy. Method: Twelve patients with congenital hemiparesis underwent presurgical fMRI. All had cortical resections and were re-scanned 12 to 36 months after surgery. Activation maps were superimposed over anatomical images; analysis using Student t test with a P<0.0001. Limbs were evaluated with neurological exam in 12 to 36 months. Result: Pre-operatively, fMRI showed 3 main patterns. The first showed activation of PMC adjacent to the destructive lesion. The second was characterized by absence of activation of the PMC ipsilateral to the lesion; and activation in the normal hemisphere. A third displayed bilateral activation of PMC. Postoperatively, patients who did not have activation of the motor cortex adjacent to the lesion regained activation, and that was accompanied by improved motor function. Conclusion: These findings suggest that the PMC in the lesioned hemisphere may play a role in the motor function of the paretic limbs. Furthermore, the post-operative activation of previously silent PMC in some patients suggests that recurrent seizures and epileptogenic discharges may inhibit potentially preserved function. The improved motor function accompanied these positive fMRI changes adds credibility and raises the issue of new therapeutic.
p112 CAVERNOUS MALFORMATIONS SURGICAL EPILEPSY SERIES R. M. Buentello Garca*, C. Domnguez Rico*, D. San Juan Orta*, H. Sentes Madrid, E. Brust Mascher*, and M. A. Alonso Vanegas* *Instituto Nacional de Neurologa y Neurociruga, Distrito Federal, Mexico; and Instituto Nacional de Nutricin y Ciencias Mdicas Salvador Zubirn, Distrito Federal, Mexico
Purpose: To describe our surgical serie of patients presenting cavernous malformations and intractable epilepsy. Method: We retrospectively reviewed our series of 68 patients who underwent complete lesion/epileptogenic zone resection, operated at the National Institute of Neurology and Neurosurgery and the ABC Medical Center in Mexico City, from January 2005 to December 2011. Inclusion criteria were: patients presenting with diagnosis of cavernous malformation and intractable epilepsy. Presurgical evaluation was carried out utilizing a modified international protocol that included among others: complete medical history, MRI, surface EEG, Video-EEG, neuropsychological testing and psychiatric evaluation, and in some selected cases fMRI. Result: Mean age of seizure onset was 26.2 (SD 12.3) years, 53.1% were men and 56.9% women, mean seizure frequency per month before surgery was 15.2 (SD 29.6). Etiology: 92.6% of patients with single cavernous malformation (29.4% extratemporal and 63.2% temporal
p114 ROLE OF NEURONAVIGATION DURING INVASIVE MONITORING FOR EPILEPSY SURGERY R. Vazquez, M. Caballero, P. M. Martinez, M. Rivero, J. Marquez, and M. D. Jimenez University Hospital Virgen del Rocio, Sevilla, Spain
Purpose: Invasive electrodes are used to localize the epileptogenic area in patients where structural lesions cannot be seen in imaging techniques or the epileptogenic focus is not in the cerebral cortex and they are used to map precisely the area where seizures arise. Method: We present a case of a 13 years-old patient with daily complex-partial seizures refractory to medical treatment. Video-EEG showed left temporal interictal epileptiform discharges and left theta temporal rhythm during ictal recording. Neuropsychological studies were normal. SPECT showed an area of hipoperfusion in mesial and anterior region of
35 Abstracts
the left temporal lobe. MRI showed a 1-cm left temporal subarachnoid cyst. Result: Electrocorticography with subdural electrodes covering left basal frontal, left mesial temporal and left lateral temporal areas where held during four days. The accuracy of electrodes location was assured by neuronavigation. Four seizures starting in left temporal mesial area where registered. A resection of the anterior left temporal pole was done with very successful outcomes. Conclusion: Neuronavigation with MRI allows us to plan before the craniotomy the desirable location of the invasive electrodes. Invasive electrodes need to be placed exactly on the epileptic focus to avoid recording spreading cortical discharges. In addition, neuronavigation allows us to double check the location of the invasive electrodes and quantify slight displacement before the surgical resection takes place. report results of VNS in our institute for its significance based on super selection of patient's types of seizures and responsiveness. Method: We selected a cohort of 9 patients who underwent VNS implantation (Cyberonics, Model 102 and 103) for intractable seizures who had comprehensive epilepsy evaluation using; long term EEG monitoring, dedicated structural and functional neuroimaging and neuropsychological evaluation. We studied their demographics, types of seizures, duration of epilepsy, seizure frequency pre and post VNS insertion. Result: We had 9 patients (5-males, 4-females) who underwent VNS surgery over a period of 4 years with average (+SD) age 20.6 (6.4) years. Duration of seizures before they underwent operation was 15.7 (6) years. Six patients had multi-focal epilepsy with secondary generalization and three had primary generalized epilepsy. Average duration of follow up post VNS insertion was 18.4 (+11.3) months. Mean seizure frequency was 32.4 (range: 3180) per month. Seizure frequency post surgery was 5.4 (range: 3630) per month. All but 1 had >50% improvement in seizure frequency. 7 patients improved by >70% with 1 patient being seizure free. There was no statistically significant correlation to the type of seizure and response. Conclusion: About >70% responder rates were seen in our cohort which is higher probably because of super-selection of patients after comprehensive epilepsy evaluation. VNS should be considered for patients with intractable epilepsy who are not good candidates for epilepsy surgery.
p115 TEMPORAL LOBE EPILEPSY SURGERY RESULTS OF AN EPILEPSY SURGERY UNIT WITH UP TO TEN YEARS FOLLOW UP S. Gatzonis*, N. Georgakoulias, A. Siatouni*, C. Tsekou*, T. Bouras*, E. Aggelopoulos*, M. Papathanassiou*, E. Aggelakis*, P. Patrikelis*, I. Kaskarellis*, E. Patsouris*, and D. Sakas* *Athens Medical School, Athens, Greece; and Athens General Hospital G. Genimatas, Athens, Greece
Purpose: The surgical therapy of epilepsy is nowadays an established therapy of drug resisting (dr) partial epilepsy especially for temporal lobe epilepsy (TLE). Surgical procedures for drTLE result in a curative effect with no mortality and minimal serious side effects. We present the protocol of the presurgical evaluation of patients with drTLE, the surgical procedures and the results from a single center. Method: 47 patients aged 15- 63 ys, 22 men and 25 women who were proposed for surgical therapy for drTLE. 37 patients suffered from welldefined medial temporal lobe (MTLE) syndrome. Based on patients history, interictal EEGs, long term video-EEG, Wada test and neuropsychological evaluation they underwent surgery such as antero-medial temporal lobectomy modified by Spencer or selective amygdalohippocampal excision. Individualized procedures were performed in some of the other patients based on long term electrocorticography or/and intraoperative recordings. Result: 64, 9% (24/37) of the patients with drug-resisting epilepsy of the mesial temporal lobe are classified as Engel I after the surgical procedure. Nine patients show worthwhile seizures reduction (Engel II, III) and 2 patients do not show any appreciable improvement (Engel IV). Two patients did not present at the follow-up. The percentage of patients suffered from drTLE due to structural lesions who were proposed for surgical therapy and remains seizure free is 60% (6/10). Serious permanent side effects: one patient remains with left hemiparesis. Conclusion: Drug-resistant temporal lobe epilepsy is a syndrome with a very good response to surgical treatment. Our results are in concordance with the literature.
p117 SEIZURE REDUCTION AFTER DEEP BRAIN STIMULATION IN A PATIENT WITH PARKINSON DISEASE ASSOCIATED WITH IDIOPATHIC GENERALIZED EPILEPSY T. Hoshida*, N. Maruyama*, Y. Sawai*, K. Kawata*, H. Hirabayashi*, K. Tamura, and H. Nakase *National Hospital Organization, Nara Medical Center, Nara, Japan; and Nara Medical University, Kashihara, Japan
Purpose: We report a case of seizure reduction after deep brain stimulation (DBS) of the subthalamic nuclei (STN) in a patient with idiopathic generalized epilepsy and Parkinson disease. Method: A 61-year-old woman had experienced her first seizure at 10 years of age. Generalized tonic-clonic seizures occurred during sleep. Her seizures occurred several times per year while she was taking 800 mg valproate. She also started experiencing bradykinesia and limb tremor at 51 years of age. She was diagnosed with Parkinson disease and received medical treatment. She was finding it difficult to walk; as a result, she was referred to the neurosurgery department for DBS surgery at 54 years of age. Result: Presurgical evaluation revealed no epileptic discharges during long-term electroencephalography monitoring. Valproate was discontinued and STN-DBS was performed uneventfully. Bradykinesia and bilateral tremor improved markedly after DBS. When the estimated electrical current was changed from 31.9 to 12.2 microampere at 5 months after DBS, the first postoperative seizure occurred, and administration of 400 mg valproate was restarted. One year later, when the estimated electrical current was changed from 29.3 to 15.6 microampere, the second and third postoperative seizures occurred. The estimated current was changed from 15.6 to 20.5 microampere and the patient was administered 400 mg of valproate, after which she has remained seizure free for 5.5 years. Conclusion: Stimulation current conditions may be responsible for generalized seizure. The comorbidities of idiopathic generalized epilepsy and Parkinson disease showed improvement after STN-DBS. However appropriate stimulation conditions are required for seizure reduction.
p116 HIGHER RESPONDER RATES TO VAGAL NERVE STIMULATION: IN SUPER-SELECTIVE PATIENTS S. Sinha, E. Khalid, F. Bamogaddam, M. Flatah, A. J. Sabbagh, and K. A. Siddiqui National Neurosciences Institute, King Fahad Medical City, Riyadh, Saudi Arabia
Purpose: Vagal nerve stimulator (VNS) is a well recognized treatment for intractable epilepsy patients with upto 50% reduction in seizures. We
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p118 WHOLE EXOME SEQUENCING WITHIN AN IRISH PEDIGREE OF IDIOPATHIC GENERALISED EPILEPSY M. Mccormack*, G. D. OConnor, E. Heinzen, K. V. Shianna, J. Conroy, S. Ennis, D. Goldstein, N. Delanty, and G. L. Cavalleri* *Royal College of Surgeons in Ireland, Dublin, Ireland; Beaumont Hospital, Dublin 9, Ireland; Duke University, Durham, USA; and University College Dublin, Dublin, Ireland
Purpose: Approximately 40,000 people in Ireland are diagnosed with epilepsy. Beaumont Hospital is the major tertiary referral centre for epilepsy in Ireland and through clinics we have recruited pedigrees with strong familial patterns of seizures, providing a resource for identifying causal mutations in the Irish population. Method: We present a large Irish pedigree containing 21 family members across three generations of which 8 individuals have a diagnosis or suspected history of epilepsy, including absence seizures. We performed whole exome sequencing on two siblings with idiopathic generalised epilepsy (IGE) and a third sibling with localisation-related epilepsy (LRE). Result: From our analysis we limited candidate variants to those that are shared between affected individuals, functional and rare (<3% minor allele frequency in general population). Resulting candidate causal variants included two novel non-synonymous SNPs in SLC2A1, a gene that encodes the glucose transporter type 1 (GLUT1). Follow-up sequencing among the extended pedigree showed near complete segregation with a seizure phenotype. Genotyping in a large combined cohort of sporadic epilepsy cases and population controls is currently ongoing to establish the background frequency of these variants in the Irish population. Conclusion: Through whole exome sequencing in just three individuals we have identified mutations in SLC2A1 as credible causal variants for IGE and/or LRE in an Irish pedigree. It remains to be seen if these specific risk variants contribute to more sporadic forms of epilepsy. These findings mirror recent discoveries which identified a defect in GLUT1 as a rare cause of IGE in patients with absence seizures.
both patients seizures started in infancy and occurred in clusters, mainly provoked by fever, but in the first one their frequency decreased with age, while in the second one a tendency to epileptic status was present. Conclusion: Both cases confirm that seizures in clusters, initially provoked by fever, are the most common epilepsy phenotype within EFMR. Our first case is among the very few reported, where a heterozygous female PCDH19 mutation carrier did not manifest any clinical features. In our case totally skewed X-inactivation is a possibility that might explain the lack of clinical history in patient's mother, although it is not in correlation with previous study. Acknowledgments: The study was supported by Grant #49/2011, Medical University - Sofia, Bulgaria.
p120 BORDERLINE DRAVET SYNDROME - BROADENING THE PHENOTYPIC SPECTRUM OF PYRIDOXINEDEPENDENT EPILEPSY A. Baumgart*, M. Van Kempen, N. Verhoeven, R. Stensbjerre Mller, R. Boor, H. Muhle*, J. Albers*, L. L. Klitten, H. Hjalgrim, D. Lindhout, U. Stephani*, I. Helbig*, and S. Von Spiczak* *University Medical Center Schleswig-Holstein, Kiel, Germany; University Medical Centre Utrecht, Utrecht, The Netherlands; Danish Epilepsy Centre, Dianalund, Denmark; and Northern German Epilepsy Centre, Schwentinental/Raisdorf, Germany
Purpose: Pyridoxine dependent epilepsy (PDE) and pyridoxal-5-phosphate deficiency are rare autosomal recessive enzyme defects in vitamin B6 metabolism due to mutations in the ALDH7A1 and PNPO gene. The phenotypic variability, however, is broad. The aim of this study was to asses the frequency of vitamin B6 deficiencies in unexplained infantile epilepsy. Method: We screened 113 patients with unclear epilepsy syndromes starting in the first year of life for mutations in ALDH7A1 and PNPO. Mutation analysis of the entire coding region of both genes including adjacent splice sites was performed. Result: No pathogenic mutations in PNPO were found. Sequence analysis of ALDH7A1 identified one patient as compound heterozygous for both a novel, likely pathogenic c.1468A>G; p.Arg490Gly variant and a known mutation c.1195G>C; p.Glu399Gln. The patient had a single neonatal seizure on postnatal day 5. In the course of the disease, he presented with a Dravet-like phenotype including alternating hemiclonic seizures, prolonged seizures with febrile infections, theta rhythms and generalized discharges on the EEG and developmental delay plateauing from the age of 2 years onwards. Partial response to antiepileptic drugs was observed as well as long seizure-free periods in adolescence. The patient never received pyridoxine treatment and died at age 31 from epileptic status prior to genetic diagnosis. Conclusion: PDE should be considered in infants with severe epilepsies including Dravet-like phenotypes. PDE may result in atypical phenotypes mimicking well-defined epilepsy syndromes with partial response to anticonvulsive drugs and seizure-free periods without pyridoxine treatment.
p119 PILOT STUDY FOR PCDH19 GENE TESTING IN BULGARIA P. Dimova*, A. Kirov, A. Todorova, T. Todorov, B. Sukhudyan, V. Bojinova*, and V. Mitev *St. Naum University Hospital of Neurology and Psychiatry, Sofia, Bulgaria; Medical University, Sofia, Bulgaria; and Arabkir Joint Medical Center and Institute of Child and Adolescent Health, Yerevan, Armenia
Purpose: To report the results of the first genetic study for detection of PCDH19 mutations in Bulgaria. Mutations in this gene cause the Xlinked Epilepsy and Mental Retardation Limited to Females (EFMR), which is characterized by seizure onset in infancy or early childhood, cognitive impairment, and large phenotypic, including intrafamilial variability. Usually, the PCDH19 mutations arise de novo, or are inherited by the unaffected carrier fathers or by affected mothers. Method: Whole PCDH19 gene sequencing was performed in 10 female patients with early onset epileptic encephalopathy. Result: The molecular genetic study showed two novel PCDH19 mutations - c.2705dupA; p.Asp902Lysfs*6, and c.1091delC; p.Pro364Argfs*4. In the first case, the healthy mother was a heterozygous asymptomatic carrier. The second mutation c.1091delC was de novo. In
p121 PAEDIATRIC DIAGNOSIS NOT MADE UNTIL ADILTHOOD: A CASE OF WOLF-HIRSCHHORN SYNDROME A. Coppola*, V. K. Chintaphalli*, P. Hammond, J. W. Sander, and S. M. Sisodiya *Institute of Neurology, University College London, London, UK; UCL Institute of Child Health, London, UK; Heemstede, The Netherlands; and UCL Institute of Neurology, London, UK
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Purpose: Wolf-Hirschhorn Syndrome (WHS) is a well-known syndrome caused by 4p terminal deletion. The distinctive clinical features (facial dysmorphism, somatic defects, neurological impairment and seizures) typically lead to a genetic diagnosis early in life. Seizure onset is typically within the first year of life with febrile seizures, sometimes leading to status epilepticus. Seizures tend to improve/cease with age. We report on a person in whom the diagnosis was only made in adulthood through array-CGH. Method: The patient is aged 34 years. At 7 months she experienced a tonic-clonic convulsion, at 10 months spasms, at 3 years convulsive status epilepticus and at 13 atonic seizures. At 23, she came under our care. Examination showed moderate learning disability and minor dysmorphisms, but no syndromic diagnosis was made despite three clinical genetics reviews. Her epilepsy has always been drug-resistant. Currently, she continues to experience 13 seizures/month, exacerbated by high temperature. Genome-wide comparative genomic hybridization and three-dimensional quantitative facial analysis have been performed. Result: Array-CGH showed a 1.8 Mb 4p16.3 deletion. 3D quantitative facial analysis classified her subtle facial dysmorphism as WHS-like. Conclusion: This case highlights several issues: milder dysmorphic features can be missed by clinical examination; quantitative facial analysis can suggest diagnosis; array-CGH is an important diagnostic tool in adults with drug-resistant epilepsy and additional features, even when clinical diagnoses have not been made; the phenotypic spectrum of even well-known syndromes may be broader than typically appreciated.
p123 HIPPOCAMPAL SCLEROSIS WORSENS ADNFLE PHENOTYPE RELATED TO CHRNB2 MUTATION A. Labate*, L. Mumoli*, A. Fratto*, A. Quattrone*, and A. Gambardella *University Magna Graecia Catanzaro, Catanzaro, Italy; and Institute of Neurological Sciences, Mangone (CS), Italy
Purpose: Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a distinct epileptic syndrome with a broad range of severity even among affected members of the same pedigree, and the level of pharmacoresistance may reach 30%, close to that seen in sporadic focal epilepsies. Method: To investigate this issue of phenotypic heterogeneity, we carried out a high-resolution MRI study in the ADNFLE family carrying the V287L mutation of the CHRN beta2 subunit (CHRNB2), which includes one pharmacoresistant patient. All 10 affected members were prospectively examined using a 3 Tesla MR750 GE MRI scanner with a 8-channel head coil, based on a protocol routinely used at our clinic for patients with epilepsy. MRI studies were evaluated in a manner blinded to the electro-clinical data. Result: The brain MRI was normal in all affected individuals except the right-handed 22 year-old girl (member III-7) with normal intellect, who had refractory seizures and typical radiological signs of left hippocampal sclerosis (Hs). She had also had febrile seizures at age of 10 months. Conclusion: The results of this study illustrate that Hs has offered a fertile substrate to develop intractable ADNFLE.
p122 DISTRIBUTION OF ELP4 POLYMORPHISMS IN ROLANDIC EPILEPSY PATIENTS IN RELATION TO CLINICAL PARAMETERS A. Gkampeta, L. Fidani, E. Pavlou, T. Katopodi, and F. Athanasiadou-Piperopoulou Aristotle University of Thessaloniki, Thessaloniki, Greece
Purpose: Rolandic epilepsy (RE) is one of the most frequent epileptic syndromes in children. ELP4 is a component of the elongator complex, involved in transcription and tRNA modification. The aim of this study was to investigate the possible effect of ELP4-Ear1 and ELP4-BsrGI genotypes to specific clinical characteristics of children with RE. Method: 31 children from northern Greece diagnosed with RE (age range: 416 years) were genotyped for the ELP4-Ear1 and ELP4-BsrGI polymorphisms. The polymorphisms were detected with a PCR-RFLP method, after designation of specific primers, PCR amplification and enzyme digest of the relevant fragment. The relationship of ELP4 polymorphisms to clinical characteristics such as electroencephalographic (EEG) features, type of seizures and response to medication were rated with the Chi-square test of independence. Result: ELP4-Ear1 polymorphisms (A/A, G/G, A/G) when compared with EEG features, type of seizures and response to medication did not show any significant difference (P=0.681, P=0.359 and P=0.454 respectively). Similarly, neither ELP4-BsrGI polymorphisms (G/T, G/G, T/T) showed any significant difference (P=0.599, P=0.704 and P=0.787 respectively). Conclusion: The presence of ELP4-Ear1 G allele was associated with bilateral EEG features, while the ELP4-BsrGI G allele associated with lateral EEG features and a better outcome with complete control of seizures for more than two years after seizure onset. Further studies in larger cohort of patients are needed in order to clarify the effect of ELP4 genetic variations on clinical parameters in children with RE.
p124 EUROEPINOMICS RES AR WORKING GROUP - A SHARED RESOURCE FOR THE IDENTIFICATION OF RISK FACTORS IN AUTOSOMAL RECESSIVE EPILEPSIES A. Suls*, S. Weckhuysen*, P. De Jonghe*, and A. W. G. Euroepinomics Res Crp *VIB, Wilrijk, Belgium; and http://bree.cs.nott.ac.uk/ euroepinomics/index.php/projects-crps/res-main, Europe
Purpose: The aim of the autosomal recessive (AR) working group of the EuroEPINOMICS consortium on rare epilepsy syndromes (RES) is to elucidate the role of AR variants in epilepsies, as this is for the moment not well documented. Method: Within the consortium we collect all families that are or can be compatible with an AR mode of inheritance. We apply homozygosity mapping in a subtype of families followed by whole exome sequencing (WES) and copy number variation analysis to identify causal variants. Result: We ascertained within our consortium 23 consanguineous epilepsy families and 32 sibs with different types of epileptic encephalopathies (EE). Collection of additional families is an ongoing effort. In consanguineous families homozygous variants are most likely causing the disease. By performing homozygosity mapping on one consanguineous epilepsy family we could identify a disease locus on chromosome 21 (~9Mb). The analysis of the sequencing data of this locus is ongoing. If no homozygous variants/locus is identified in these families, other genetic hypotheses will also be tested on the generated data. In sibs with EE several genetic hypotheses are tested: homozygous model, compound heterozygous model and de novo mosaic autosomal dominant model. Analysis of WES data on the sib pairs is ongoing. Conclusion: The large amount of families with different ethnical backgrounds compatible with an AR mode of inheritance we collected and the preliminary genetic data we generated shows furthermore that recessive variants are likely to cause some genetic epilepsies. Further genetic analyses will elucidate the proportion of AR inheritance in epilepsies.
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p125 IDENTIFICATION OF A NOVEL GENE IN A FAMILY WITH SEVERE INFANTILE-ONSET EPILEPSY C. Depondt*, Y. Hitomi, E. Heinzen, S. Donatello*, H. Dahl, S. Berkovic, I. E. Scheffer, B. Legros*, M. Pandolfo*, D. Goldstein, and P. Van Bogaert* *Universit Libre de Bruxelles, Brussels, Belgium; Duke University, Durham, USA; and University of Melbourne, Melbourne, Australia
Purpose: To describe the clinical characteristics, genetic analysis and functional studies in a family with autosomal recessive, infantile-onset epilepsy and psychomotor retardation. Method: We identified a family with 3/3 siblings with infantile-onset epilepsy and psychomotor regression. Two siblings were exome sequenced. Shared homozygous, novel variants were sequenced in all 3 siblings and their parents. Result: Onset of focal seizures was between 19 and 35 months and psychomotor regression occurred soon after. Seizures were refractory to medical treatment. Exome sequencing identified a homozygous missense variant in the gene TNK2, encoding a brain-expressed tyrosine kinase. All 3 siblings were homozygous for the variant and both parents were heterozygous. Genotyping of the variant in 3034 patients with epilepsy and 1663 controls revealed no further homozygotes and very low frequencies of heterozygotes (0.002). Sequencing of all 15 exons and splice sites of the TNK2 gene in 110 patients with infantile-onset epilepsies, as well as analysis of next-generation sequencing data in 131 cases with genetic generalized epilepsies and 297 controls showed no enrichment of putative functional variants in cases compared to controls, although heterozygous truncating variants were overrepresented in patients with severe infantile epilepsy. Functional studies demonstrated that the identified variant abolishes NEDD4 binding to TNK2, preventing its degradation after epidermal growth factor stimulation. Conclusion: The combined results of our genetic and functional studies suggest TNK2 as a novel gene for severe infantile-onset epilepsy. Definitive confirmation of pathogenicity will require identification in unrelated patients. Result: The epilepsy phenotypes due to p.Arg1596 substitutions in all three families fit to the spectrum of GEFS+. The epilepsy phenotypes differ between probands and in mutation carriers range from asymptomatic, through FS, GEFS+ to borderline DS and focal seizures. In all families, we were able to analyse three generations and we observed the worsening of the symptoms in following generations. Conclusion: The differences in clinical DS/GEFS+ picture resulting from the mutations of the same residue in the SCN1A gene may suggest involvement of genetic modifiers in final phenotype development.
p127 PHENOTYPING DRUG RESPONSE IN EPILEPSY E. Caruana Galizia, K. Chinthapalli, J. Novy, J. W. Sander, and S. M. Sisodiya Institute of Neurology, London, UK
Purpose: Little attention has been given to the spectrum of drug response in epilepsy. With a much recognized need for multicentre collaborations, case definition will be key for appropriate case ascertainment. We propose definitions for different response groups in patients exposed to levetiracetam and demonstrate the emergence of six different response patterns. Method: All data were collected retrospectively by accessing patient medical. The following definitions were applied in order to classify the response pattern: the seizure-free group was defined as those cases that achieved seizure freedom for a minimum of 12 months; partial responders were defined as any case in which the number of seizures improved by >25% from baseline; non-responders were defined as those cases with no more than a 25% fluctuation above or below baseline; seizure-worsening was defined as >25% worsening of seizure frequency from baseline. Result: Data were collected on 859 individuals and were distributed within the different response groups as follows: Seizure free group, 105 cases; Partial responders, 147 cases; Non-responders, 92 cases; Seizure worsening, 82 cases. Response could not be classified in 242 cases. Two other response patterns emerged: response before return to baseline (48 cases) and response before worsening (45 cases). Conclusion: We demonstrate that for the majority of cases the pattern of drug response can be classified into one of six different response-phenotypes. This work lays down the foundations for phenotyping of drug response in much needed multi-centre studies in epilepsy pharmacogenetics.
p126 CLINICAL VARIABILITY RESULTING FROM THE MUTATIONS AT THE P.ARG1596 RESIDUE IN THE SCN1A GENE D. Hoffman-Zacharska, E. Szczepanik, R. Tataj, I. Terczynska, ska-Ciuchta, Z. Zalewska-Miszkura, D. AntczakA. Goszczan Marach, and J. Bal Institute of Mother and Child, Warsaw, Poland
Purpose: SCN1A, the gene encoding the sodium channel alpha 1 subunit, is one of the most important epilepsy genes. Mutation in SCN1A are associated with various types of epilepsy. The clinical spectrum of SCN1A mutations ranges from benign FS through spectrum of GEFS+ to severe epilepsy syndromes such as Dravet Syndrome (DS) and intractable childhood epilepsy with generalized tonic-clonic seizures (ICEGTC). All identified SCN1A mutations are dominant and usually occur de novo, however familial cases also are described (510%). In the most families proband, shows the severe form of disease, while the remaining family members milder GEFS+ spectrum. We present unrelated DS/ GEFS+ families, where disease is caused by missense mutations at residue p.Arg1596 of the Nav1.1 protein. Method: Three unrelated multi-generations families with p.Arg1596 missense mutations p.Arg1596His (2 families) and p.Arg1506Cys in the SCN1A gene were enrolled into the study. Mutations were identified by direct sequencing of the SCN1A gene. Phenotypes of epilepsies were classified according to ILAE classification.
p128 GLRB IS THE 3RD MAJOR GENE-OF-EFFECT IN HYPEREKPLEXIA S. K. Chung*, C. A. Hunt*, A. V. Derrick*, T. D. Cushion, S. E. Wood*, C. Drew*, O. W. Howells*, R. H. Thomas*, and M. I. Rees* *Institute of Life Science, Swansea, UK; and Swansea University, Swansea, UK
Purpose: Glycinergic neurotransmission is a major inhibitory influence in the central nervous system (CNS) and defects are primarily associated with paroxysmal neuromotor disorder, hyperekplexia or startle disease. The alpha1 subunit of the glycine receptor (GlyR) gene (GLRA1) and its cognate postsynaptic transporter (SLC6A5) are well-established genesof-effect in hyperekplexia, nevertheless, up to 60% of hyperekplexia cases remain gene-negative. The beta subunit of the glycine receptor (GLRB), the heteropentameric partner subunit to GlyRa1, was selected for further analysis in gene-negative cases. Method: 92 gene-negative hyperekplexia patients were selected for variation screening of the GLRB using multiplex PCR and direct Sanger sequencing approach. All variants were excluded from normal controls and mutation constructs were prepared for functional characterisation.
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Molecular modelling was also used to predict protein-damaging outcomes. Result: This study identified 9 novel GLRB mutations within 8 independent hyperekplexia index-cases accounting for approximately 9% of the gene-negative cohort. This included 5 recessive, 2 dominant and 1 compound heterozygote inheritance scenarios, and were classified as 2 nonsense, 5 indels and 2 missense variants. The biological consequence of the nonsense and indel mutations was unambiguous and the 2 missense mutations were further investigated for electrophysiological analysis. Conclusion: This study describes the largest genetic screening of GLRB in hyperekplexia and represents a 3rd major gene for hyperekplexia. It further implicates the glycinergic proteome as the basis for further analysis. Purpose: The Val66Met (rs6265) polymorphism in the brain-derived neurotrophic factor gene (BDNF) has been associated with cognitive performance as well as structural and functional hippocampal differences, in healthy controls and some clinical populations. Deregulation of BDNF expression has also been implicated in the mechanisms underlying epileptogenesis. Mesial temporal lobe epilepsy (mTLE) is the most common partial epilepsy in adults who medically refractory. Patients with mTLE usually present cognitive dysfunction with memory impairment as a prominent cognitive deficit. Approximately one third of patients also experience significant post-operative memory decline and transient language dysfunction following epilepsy surgery. Method: We investigated the association of Val66Met polymorphism with the results of cognitive tests (n=282), hippocampus volume (n=108) and fMRI data (n=47) during memory-encoding and language paradigms in a group of patients with mTLE. Result: Independently of the age, gender and seizure laterality (right or left) the patients with mTLE and carriers of met allele (n=83) had significantly lower scores in delayed memory tasks and were significantly more likely to display post-operative decline in measures of both verbal and visual memory than Val homozygotes patients (n=199). There was no significant effect of the genotype on immediate memory, fluency or hippocampus volume. fMRI activation during memory encoding and verbal fluency revealed the Met allele carriers had significantly reduced default mode network activation compared to Val/Val carriers. Conclusion: These results suggest the BDNF Val66Met polymorphism may contribute to memory function in patients with mTLE and may influence the responsiveness of the default mode network.
p129 PHARMACOGENOMICS OF VALPORATE INDUCED WEIGHT GAIN J. Chukwu*, S. Tirupathi, M. King, B. Lynch, B. Mccoy, D. Goldstein, N. Delanty**, G. L. Cavalleri*, and D. Webb *Royal College of Surgeons in Ireland, Dublin, Ireland; Royal Hospital Belfast, Belfast, UK; Children's University Hospital, Dublin, Ireland; Our Lady's children's Hospital Crumlin, Dublin, Ireland; Duke University Institute for Genome Sciences and Policy, Durham, NC, USA; **Beaumont Hospital, Dublin, Ireland; and Adelaide & Meath Hospital Incorporating National Children's Hospital Dublin, Dublin, Ireland
Purpose: Sodium valproate (VPA) is one of the most commonly used AEDs in the treatment of partial and generalised seizure disorders. Weight gain is one of the known side effects of VPA. It has been estimated that between 10 and 70% of people exposed to VPA experience some weight gain. About 10% of these patients have significant weight gain (> 10% of pre-VPA initiation weight) necessitating discontinuation of therapy. The exact mechanism of weight gain in VPA is not fully understood. This study seeks to test the hypothesis that individuals with common genetic variants associated with obesity are more prone to developing VPA-induced weight gain than those who do not. This will be explored in a paediatric cohort diagnosed with epilepsy and take VPA as antiepileptic drug. Method: Retrospective study looking at clinical phenotype of paediatric epilepsy patients in Dublin. Phenotypic data will be utilised in correlating the results with genome wide association analysis on patient DNA samples. Result: 152 patients have been recruited to the study to date. It is hoped that by December 2012, 250 individuals would have been recruited. Conclusion: Using the latest technology in the study of human genome it is hoped that the genomic factors responsible for the weight change in children with epilepsy taking valproic acid will be determined.
p131 A COMPOUND HETEROZYGOUS MISSENSE MUTATION AND A LARGE DELETION IN THE KCTD7 GENE PRESENTING AS AN OPSOCLONUS-MYOCLONUS ATAXIALIKE SYNDROME L. Blumkin*, S. Kivity, D. Lev, E. Leshinsky-Silver, and T. Lerman-Sagie *Holon, Israel; and Wolfson Medical Center, Holon, Israel
Purpose: To describe a new presentation of KCTD7 mutation: an opsoclonus-myoclonus ataxia like syndrome with subsequent development of generalized continuous epileptic activity without clinical correlation, and partial clinical response to steroid therapy. Method: We recorded the clinical course of the disease, the evaluation and the response to steroid therapy. The patient is a five-year-old boy who was diagnosed as having opsoclonus-myoclonus ataxia syndrome at the age of 16 months and was therefore treated by an OMS protocol including high dose ACTH, and later dexamethasone. After the appearance of continuous epileptic activity on recurrent video -electroencephalographic studies at the age of 3 and a half year a neurodegenerative disorder was suspected. After excluding possible genetic causes, whole genome exome sequencing was performed in order to identify the causative gene. Sequence variants were filtered according to the phenotype. Sanger sequencing was performed to confirm the point mutation and MLPA was used for screening for a possible deletion in the second allele. Result: Two pathological variants were found in the KCTD7 gene: R84W and a large deletion of exons 3 and 4. The father is heterozygous for the R84W mutation and the mother is heterozygous for the exon 3+4 deletion. Conclusion: KCTD7 mutations were described in a single family with progressive myoclonus epilepsy. Our patient presented with non epileptic myoclonus, ataxia and opsoclonus responsive to corticosteroid treatment and only two years later developed an epileptic EEG witout overt seizures. The different phenotype broadens the spectrum of KCTD7 related diseases.

p130 DOES THE BDNF VAL66MET POLYMORPHISM INFLUENCE COGNITIVE FUNCTION IN PATIENTS WITH MTLE? J. Stretton, A. Foulkes, P. J. Thompson, S. Baxendale, M. K. Sidhu, E. Williams, J. Burdett, S. M. Sisodiya, J. Duncan, and M. Matarin UCL, London, UK
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p132 SUDEP AND FAMILIAL EPILEPSY R. H. Thomas*, W. O. Pickrell*, A. J. Johnston*, C. Hammond, C. Drew*, P. Smith, and M. I. Rees *Wales Epilepsy Research Network, Swansea, UK; Guy's and St Thomas NHS Foundation Trust, London; University Hospital of Wales, Cardiff; and Swansea University, Swansea, UK
Purpose: The Wales Epilepsy Research Network has been continually recruiting epilepsy families since 2006 into genetic studies. The causes of sudden unexpected death in epilepsy (SUDEP) are yet to be fully determined but amongst competing theories are genetic causes of cardiac or respiratory failure. Method: The first eighty families recruited into our study were available for analysis. The consensus definition for SUDEP was used to identify cases (Nashef 2011) and project records and clinical notes were scrutinised for clinical characteristics. Result: Sixteen of the eighty families had a probable or definite SUDEP case; no family had two SUDEP deaths. Not one of these occurred following recruitment (and so we have no DNA for analysis) and there were no clear clinical patterns to be identified from the familial epilepsy diagnosis. It was common for the sibling of the person who had a SUDEP to be the affected index case. Conclusion: We are unable to conclude that familial epilepsy is a proven risk for SUDEP. Rather we propose that families with epilepsy that have had a SUDEP death are strongly motivated to participate in research and that investigators should not be deterred from involving them in genetic research. mutations were identified in the KIF17. 5. The mutation probably lies elsewhere in the identified homozygous region.
p134 STXBP1 MUTATIONS AS A CAUSE OF DRAVET SYNDROME S. Weckhuysen*, P. Holmgren*, A. Suls*, R. Hendrickx*, R. Steensjberre Mller, H. Hjalmgrim, G. Carvill, H. Mefford, I. E. Scheffer, and P. De Jonghe* *University of Antwerp, VIB Department of Molecular Genetics, Antwerp, Belgium; Danish Epilepsy Centre, Dianalund, Denmark; Instute for Regional Health Services, University of Southern Denmark, Odense, Denmark; University of Washington, Division of Genetic Medicine, Seattle, USA; and 7Florey Neurosciences Institutes, Austin Health, Melbourne, Australia
Purpose: STXBP1 mutations have been described in Ohtahara syndrome, West syndrome and in patients with an unclassified early onset epileptic encephalopathy. Although a phenotypic spectrum of STXBP1 encephalopathy is emerging, further delineation of the spectrum is still needed. Furthermore, the genetic cause for 20% of Dravet patients is still unknown. With this study we aimed to identify additional genes for Dravet syndrome, and to specify whether STXBP1 mutations are present in this severe epilepsy syndrome. Method: We combined two complementary strategies: STXBP1 screening was performed in a wide range of severe epilepsies including 22 patients with Dravet syndrome. Additionally whole exome sequencing (WES) was performed on a cohort of SCN1A negative Dravet patients and their parents. Findings were confirmed by classical Sanger sequencing. Result: We detected 2 de novo missense mutations in 2 patients with Dravet syndrome. c.1334A>C was detected by direct Sanger sequencing of STXBP1 and c.847G>A by WES. Seizure onset was at 6 and 11 months respectively. Both patients had febrile seizures and multiple afebrile seizure types. EEG showed multifocal epileptiform activity in both patients. Development slowed down after epilepsy onset in both patients, although in the first patient some delay was noticed already at the age of 3 months. At age 19 years he is severely mentally disabled and wheel chair bound. The second patient has a normal neurological exam. Conclusion: STXPB1 mutations are a rare cause of Dravet syndrome. Screening of STXBP1 in larger cohorts of SCN1A negative Dravet is currently ongoing.
p133 FAMILIAL MOVEMENT-INDUCED REFLEX EPILEPSY (FMIRE): A NOVEL GENETIC EPILEPSY SYNDROME WITH POSSIBLE MAPPING TO CHROMOSOME 1P S. Schirwani, and D. Crompton Institute of Genetic Medicine/Newcastle University, Newcastle upon Tyne, UK
Purpose: 1. To evaluate relative merits of various linkage and homozygosity mapping tools in a small UK family with a novel movementinduced reflex epilepsy in two siblings. Repetitive voluntary movement of any body part evokes voluntary clonus in that body part, clonus either subsided within seconds or culminates in generalized tonic-clonic seizures. 2. Attempt to identify the causative gene. Method: Various linkage analysis and homozygosity mapping methods were evaluated then applied to genome wide SNP data from the FMIRE family. Copy number variant (CNV) analysis was also performed. Candidate genes were selected from the homozygous region. The most likely candidate gene was sequenced. Result: A 2.0 Mb homozygous region was identified on chromosome 1. This region was homozygous in the affected sib-pair but not in the unaffected sibling or parents. KIF17, which is a brain specific motor protein involved in transporting ion channels, was identified as the most likely candidate gene. Sequencing KIF17 gene revealed many variants, though non of these were likely to be pathological. No pathological CNV was found, this result therefore did not contradict the homozygous model for FMIRE. Parametric linkage analysis using a recessive model did not show linkage signals. This result was expected due to small size of FMIRE family. Conclusion: 1. In Familial movement-induced reflex epilepsy voluntary movement induces focal clonus, then generalised tonic-clonic seizures. 2. Recessive inheritance is likely. 3. Homozygosity mapping identified a promising homozygous region on chromosome 1. 4. No pathogenic
p135 DENSE SURFACE MODELS OF FACE SHAPE ASSIST IN PREDICTING PATHOGENIC COPY NUMBER VARIANTS K. Chinthapalli*, E. Bartolini*, J. Novy*, M. Suttie, C. Marini, M. Falchi, Z. Fox, L. Clayton*, J. W. Sander*, R. Guerrini, C. Depondt, R. Hennekam**, P. Hammond, and S. M. Sisodiya* *UCL Institute of Neurology, London, UK; UCL Institute of Child Health, London, UK; Children's Hospital Meyer, Florence, Italy; UCL, London, UK; Universit Libre de Bruxelles, Brussels, Belgium; and **University of Amsterdam, Amsterdam, The Netherlands
Purpose: Copy number variants (CNVs) are increasingly recognised as genetic contributors to epilepsy. Pathogenic CNVs can manifest as a
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range of phenotypes, such as intellectual disability, autism, partial or generalised epilepsy syndromes, and are important to detect. Facial dysmorphism also arises from CNVs and we show that people with epilepsy related to CNVs have a more atypical face shape. Furthermore, in people with epilepsy, face shape analysis is shown to successfully predict those carrying pathogenic CNVs. Method: Stereophotogrammetry was used to capture 3D face surface images of 181 patients with epilepsy and 336 control subjects. All patients underwent molecular analysis to determine the occurrence of CNVs. Images of 118 patients and all controls were used to build dense surface models for the face, periorbital region and perinasal region. We then quantified a measurement of face shape difference (FSD) for face regions and determined correlation of FSD with occurrence of CNVs. Predictive accuracy of the correlation was tested unseen on a second group of 63 patients. Result: FSD predicted presence of a pathogenic CNV in 63 new patients with high sensitivity (80%) and specificity (78%). Within all 181 patients, 43 had pathogenic CNVs and significantly more atypical periorbital (Mann-Whitney test; p<0.001), perinasal (p<0.001) and facial (p<0.001) shapes. These differences were not explained by age, ethnicity, anti-epileptic drug use or facial injury. Conclusion: In people with epilepsy, stereophotogrammetry and face shape analysis can successfully and objectively assist in identifying those with pathogenic CNVs. This can lead to earlier diagnosis and improved management of their epilepsy.
p137 EFFECT OF UGT1A6*2 GENETIC POLYMORPHISM ON THE DOSES, PLASMA CONCENTRATION AND METABOLISM OF VALPROIC ACID IN PATIENTS WITH EPILEPSY FROM R.MACEDONIA Z. Sterjev*, G. A. Kiteva-Trencevska, J. T. Ribarska*, E. Cvetkovska, I. Kuzmanovski, I. Petrov, A. K. Nestorovska*, N. Matevska*, Z. Naumoska*, A. Dimovski*, and L. Suturkova* *Faculty of Pharmacy, Skopje, Macedonia; and University Clinic of Neurology, Skopje, Macedonia
Purpose: The GG genotype of UGTIA6 A541G polymorphism has been associated with high enzyme activity compared to the wild type AA genotype. The aim of our study was to investigate the distribution and frequency of UGTIA6*2 genotype in epileptic patients (113 VPA responders/40 VPA resistant patients) and to evaluate the effects of this polymorphisms on maintenance doses, plasma concentrations and metabolism of VPA. Method: TaqMan assay-real time PCR, fluorescence polarization immunoassay and HPLC method. Result: No statistically significant difference in the allelic frequency and genotype distribution (0.49, 0.35, and 0.15, and 0.32, 0.52 and 0.15 for AA, AG and GG genotypes, p=0.46) was determined between VPA responders and VPA resistant patients, respectively. The mean values of daily maintenance doses of VPA in patients with AA, AG and GG were: 883mg+/)350.4, 977.5mg+/)359.1 and 961.7mg+/)346.6, respectively. The values of total plasma levels corresponding to the genotypes were 367.5 133.5 lmol/L for AA, 380.2+/)111.2 lmol/L for AG and 353.6+/)122.5 lmol/L for GG genotype. The differences in doses and plasma concentrations were not statistically significant (KW test H=2.45 p=0.29 and ANOVA F=0.28 p=0.76). Patients with GG genotype were associated with higher value for Ke compared to patients with AA genotype (0.04h-1 +/) 0.01 vs 0.03h-1 +/) 0.01, respectively). Patients with GG genotype had lower values for E1/2, AUC, Mean Residence Time MRT, Cmax and Tmax of VPA. Conclusion: Our data suggest that patients with GG genotype for UGTIA6 A541G polymorphisms are associated with higher maintenance daily doses of VPA, lower plasma concentrations and faster elimination of this antiepileptic drug.
p136 ALICE IN WONDERLAND SYNDROME: EPILEPSY, MIGRAINE OR BOTH? W. O. Pickrell*, R. H. Thomas, A. J. Johnston, C. White, and M. I. Rees *Institute of Life Sciences, Swansea, UK; Wales Epilepsy Research Network, Swansea, UK; and Morriston Hospital, Swansea, UK
Purpose: We present a family where 10 members of the pedigree suffer distinct, stereotyped episodes of hyper and hyposchematia, metamorphopsia including teleopsia and pelopsia and altered time awareness consistent with the Alice in Wonderland Syndrome (AIWS). Descriptions of the episodes include sensations of time slowing and speeding, sensations of hand and jaw enlargement and feelings of being detached from reality. Amongst the 10 affected family members, 4 also have epilepsy, 1 also has migraine and 3 people only have AIWS. Method: We conducted an study of AIWS incidences in epilepsy and migraine to assess its potential as a synergistic feature bridging both phenotypes (if not more). Result: Since the first published description of AIWS in 1955, there have been several reports describing associations with migraine, epilepsy, viral Illnesses (Epstein Barr Virus and H1N1) and also drugs including topiramate and dihydrocodeine. The fact that AIWS can occur with or without migraine or typical epileptic seizures raises the question as to its exact nature is it a form of migraine, epilepsy, both (migralepsy) or neither? Conclusion: There is phenotypic overlap between migraine and epilepsy and presentation of AIWS: Mutations in genes encoding ion channels have recently been associated with both migraine and epilepsy. The abnormally high incidence of AIWS, migraine and epilepsy in this family means there is a underlying genetic cause which we are currently investigating. A biological model for the pathogenesis of AIWS could help further our understanding of both migraine and epilepsy - the two most common paroxysmal brain disorders.
p138 PHARMACOGENOMIC TESTING-BASED PERSONALIZED MEDICINE FOR EPILEPSY. ANALYSIS OF 10 CONSECUTIVE REFRACTORY EPILEPTIC PATIENTS P. E. Bermejo, A. Fraile, J. Chamorro, and E. Blanco Fundacin San Jose, Madrid, Spain
Purpose: Although 30% of all epileptic patients are resistant to antiepileptic drugs (AEDs), currently a trial-and-error approach is employed to determine the most effective AED and dosage for a patient. Pharmacogenetic testing for variations in the genes encoding drug-metabolizing enzymes and drug transporters has been proposed as a personalized medicine for these patients. The aim of this study is to describe our experience in 10 consecutive refractory epileptic patients. Method: Ten mentally retarded and refractory epileptic patients were enrolled in this study. A genetic test (Neurofarmagen epilepsy) for measurement of 11 genetic variations of single nucleotide polymorphisms was performed. Number of pharmacogenetic variations, AEDs affected for these pharmacogenetic variations, antiepileptic therapy modifications, clinical improvement of the patients and decrease of seizures were collected and analyzed. Result: All enrolled patients displayed pharmacogenetic variations (3.80.8) and all of them showed affected AEDs (7.84.2). Most
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frequently involved genes were ACBC1, SCN1A and EPHX1. According to these results, antiepileptic therapy was modified in 7 patients (70%) including AEDs changes and their dosages. A clinical improvement was achieved in 5 patients (50%): 3 of them obtained a better control of their epilepsy while 2 of them achieved a better side effects profile. Conclusion: Personalized medicine for epilepsy based on pharmacogenomic testing is a new avenue for optimizing AED therapy. According to our results, some refractory epileptic patients may benefit from pharmacogenetic testing for variations in the genes encoding drug-metabolizing enzymes and drug transporters of AEDs. More studies are warranted to confirm these results. assumed a recessive model, either homozygous or compound heterozygous in the multiplex families, while in the sporadic cases a de novo mutation is an additional possibility. Whole exome sequencing was performed to identify candidate mutations. Result: So far, we have identified mutations in X-linked genes CDK16 and GABRE as possible candidates in male patients. Further analysis of the remaining families may identify more candidate mutations. To confirm their pathogenicity, we will combine our results with those of other research groups. Conclusion: Whole exome sequencing can be used to identify genetic causes for monogenic disease when performed in families.
p139 EXPANDING THE ROLE OF COPY NUMBER VARIATION IN EPILEPSY PATHOLOGY L. Addis, D. A. Collier, and D. K. Pal Institute of Psychiatry, King's College London, London, UK
Purpose: Copy Number Variation (CNV) has a well-documented association with epilepsy. We seek to expand the genotype-phenotype relationships between epilepsy and other neurodevelopmental disorders with CNV using the clinical genetics database, Brain and Body Genetic Resource Exchange (BB-GRE). Method: 10,397 individuals referred for cytogenetic investigation were analysed for CNV using a customized 44K Agilent comparative genomic hybridization (aCGH) array. aCGH results were entered into BB-GRE. We searched BB-GRE for the phenotype epilepsy or seizure. Cases were compared with controls in DECIPHER and DGV databases. Result: We identified 186 patients with epilepsy or seizures. 63% of these patients also had developmental delay or intellectual disability. 30% reported ADHD, speech/language problems or autism. We found 23 patients with large CNVs at known neurocognitive disorder hotspots; 16p11.2 (n=8), 15q13.3 (n=6), 22q11.21 (n=4), 16p13.11 (n=3), 1q21.1 (n=2). Another patient had a large novel deletion of 11.7Mb on 1p36. Several patients had disruptions of known epilepsy genes: a double deletion of only CNTNAP2 (n=1) a deletion of KCNQ2 and CHRNA4 (n=1), duplications of both CDKL5/STK9 and MECP2 on ChrX (2 male). Several patients harboured novel microdeletions or duplications. Conclusion: Our large clinical genetics database confirms and expands the role of CNV in the pathology of the epilepsies, especially the comorbidity with neurodevelopmental disorders. Identified CNVs frequently occurred in known hotspots or epilepsy genes. Rare or de-novo CNVs containing potentially pathogenic gene aberrations will be investigated further. The BB-GRE database and the clinical genetics service are important to drive genotype-based diagnoses and the delineation of genomic syndromes.
p141 PRELIMINARY DATA ON THE USE OF MTOR INHIBITORS FOR MANAGEMENT OF REFRACTORY SEIZURES AND FOR THE MANAGEMENT OF SUBEPENDYMAL GIANT CELL ASTROCYTOMAS IN PATIENTS WITH TUBEROUS SCLEROSIS COMPLEX M. Cardamone, D. Flanagan, D. Mowat, S. Kennedy, M. Chopra, and J. A. Lawson University of New South Wales, Sydney, NSW, Australia
Purpose: Background: Tuberous sclerosis complex (TSC) is a genetic disorder involving the mammalian target of rapamycin (mTOR) second messenger pathway. This results in non-malignant tumours such as subependymal giant cell astrocytomas (SEGAs) and also complex pathways leading to intractable epilepsy. Aim: To evaluate the efficacy and side effects of mTOR inhibitors in patients with TSC and intractable epilepsy and or SEGA. Method: A retrospective single centre series of 5 patients with TSC and refractory seizures treated with Rapamycin. An additional 7 patients with TSC and SEGA who received Rapamycin (R) or Everolimus (E), both mTOR inhibitors for non-surgical management between 2010 and 2012. Medical records and MRI brain imaging were reviewed to assess seizure control, side effects, and surveillance performed. SEGA volumes were assessed longitudinally using 1.5T MRI and using the Analyze software. Result: Seizure efficacy: One participant experienced seizure freedom and another experienced >90% seizure reduction. Another experienced a >50% seizure reduction. Three patients reported subjective improved learning. SEGA reduction: By three months of treatment there is statistically significant reduction in the SEGA volumes in at least 2 patients who received mTOR inhibitors (p<0.006). All seven patients had reductions of SEGA at 6 months by 3765% Side effects: Aseptic meningitis requiring hospitalisation (1 patient), dyslipidaemia (3 patients), and anorexia (1 patient). Conclusion: Preliminary data suggests mTOR inhibitors may be useful for controlling seizures in patients with TSC who are refractory to anticonvulsants and for reducing the volume of SEGAs in patients with TSC. Only one patient had a significant adverse event (aseptic meningitis).
p140 IDENTIFYING GENES INVOLVED IN EPILEPTIC ENCEPHALOPATHY BY WHOLE EXOME SEQUENCING IN FAMILIES E. H. Brilstra, R. Van T Slot, S. Van Lieshout, B. Koeleman, and C. G. F. De Kovel UMC Utrecht, Utrecht, The Netherlands
Purpose: Epileptic encephalopathies are characterized by slowing or regression of development that is attributed to epileptiform activity. When no external cause is prevalent, the condition is assumed to be genetic. In some families, multiple sibs are affected. A few genetic causes for epileptic encephalopathy are known, but many cases cannot be explained. Probably, there is high genetic heterogeneity. We aim to identify new genes as causes for these encephalopathies. Method: We have collected patients with healthy parents. Five families had multiple affected sibs, ten patients had no affected relatives. We

p142 IDENTIFICATION OF A NOVEL GENETIC LOCUS FOR FEBRILE SEIZURES IN A MALTESE FAMILY C. Farrugia*, M. Cassar, and J. Mifsud* *University of Malta, Msida, Malta; and MLSBioDNA, Paola, Malta
Purpose: The aim of this study was to narrow down a previously identified region of about 20cM on chromosome 20 linked to familial febrile
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seizures (FEB) by performing another linkage study using short tandem repeat (STR) markers. Method: The study was carried out on a Maltese three generation family having seven members with a phenotype compatible with FEB. A total of seven STR markers, from D20S1085 until the end of the telomere, at an average spacing of 2cM were genotyped in the thirteen family members using fluorescent methods. Following genotyping, multipoint parametric and non-parametric linkage analysis were performed. Penetrance was given to be 0.9. Result: The previously identified linkage region was confirmed and reduced to approximately 5cM on cytogenic band 20q13.3. Assuming autosomal dominant inheritance with incomplete penetrance, the highest logarithm of the odds score was 2.67 (p Conclusion: This study has identified a novel locus of interest associated with the FEB phenotype in a Maltese family, thus contributing to a better understanding of the syndrome and adding to the growing knowledge of the genetics of such complex diseases. Purpose: The epilepsies are a very heterogeneous group of common neurological disorders comprising many individually rare diseases. Thus, genetic diagnosis oft remains difficult. With our approach we aim to reveal the genetic basis of epileptic disorders in so far unresolved cases. Method: We enriched a panel of 323 epilepsy-associated genes using a custom designed Agilent SureSelect in solution kit and sequenced on a SOLiD 4 platform. Result: We screened >50 unknown cases with a broad spectrum of epilepsy phenotypes. We detected causative aberrations in commonly mutated ion channel genes (e.g. SCN1A, SCN2A) as well as in rarely affected genes (e.g. STXBP1, MFSD8). Surprisingly, we detected many mutations in extremely uncommon genes (e.g. KCTD7, ARHGEF9, KCNJ10, SMS). We also revealed SCN1A mutations in three patients where conventional testing (Sanger sequencing/HRM) failed to detect the mutations. Conclusion: We have successfully established a fast and cost efficient genetic screening method for patients with seizure disorders. We were able to uncover the genetic basis of many so far unresolved cases with epilepsy. We detected mutations in patients with both clear and unspecific epilepsy phenotypes. We revealed false negatives in conventional genetic testing methods. Many mutations were detected in genes that only in very rare instances have been associated with epileptic disorders. Thus, many rare epilepsy disorders might perhaps be more common but simply underdiagnosed due to unspecific and diffuse phenotypes. Therefore, our approach may contribute in collecting information on both well-known and unacquainted epilepsy disorders and in revealing their true phenotypic spectrum.
p143 CHROMOSOMOPATHIES AND EPILEPSY J. P. Domingos, F. Correia, and J. Chaves Hospital de Santo Antnio, Centro Hospitalar do Porto, Porto, Portugal
Purpose: Chromosomopathies may originate CNS malformations, associated with cognitive impairment. Although being a rare cause, they constitute a risk factor for epilepsy. They are typically related to certain types of epilepsy. Method: We present 9 patients with chromosomopathy and epilepsy followed in our outpatient clinic. Result: 1 58 year-old woman, Trisomy 21, generalized epilepsy with generalized tonic-clonic seizures (GTCS) controlled with valproic acid (VPA) 500+500mg/day. 2 56 year-old woman, Trisomy 21, senile myoclonic epilepsy, not controlled with levetiracetam 1000+500mg/day. 3 9 year-old boy, free Trisomy 21, generalized epilepsy with GTCS, controlled with VPA 200+200mg/day. 4 45 year-old man, Klinefelter syndrome, generalized epilepsy with GTCS controlled with VPA 500+1000mg/day. 5 -20 years-old man, fragile X syndrome, generalized epilepsy with GTCS, controlled with VPA 200+200mg/day. 6 37 yearold woman, 3p25 Deletion, juvenile absence epilepsy controlled with VPA 500+500mg/day. 7 31 year-old woman, trisomy 15, probably symptomatic focal epilepsy with subependymal heterotopia controlled with topiramate 50mg/day. 8 22 year-old woman, ring chromosome 20 syndrome, severe symptomatic encephalopathy with febrile seizures and recently GTCS under VPA (2ml+2ml/day). 9 - 19 year-old man, fragile X syndrome, neonatal seizures, sensory seizures, controlled with oxcarbazepine 600+600 mg/day. Conclusion: Trisomy 21 was the most frequent cromosomopathy found. These patients have a bimodal distribution: in those starting after 50 yearold an association with GTCS and senile myoclonic epilepsy is described. Deletion 3p25 is usually associated with febrile seizures and developmental delay, unlike our patient. The association between chromosome 15 and subependymal heterotopia is not described.
p145 EARLY EPILEPTIC ENCEPHALOPATY: A PECULIAR GENETIC CASE P. Guimares*, M. Santos*, R. Choro*, J. S, and I. Carrilho* *Centro Hospitalar do Porto - Hospital Maria Pia, Oporto, Portugal; and Hospital Peditrico do Centro Hospitalar de Coimbra, Coimbra, Portugal
Purpose: To present the case of a child with a deletion in the STXBP1 gene with a peculiar electroclinical presentation and good outcome. Method: Case Report. Result: We describe a five years-old girl, with development marked by cognitive delay and early-onset epilepsy. Seizures started in the neonatal period predominantly with sleep related episodes that occurred in clusters, and with pleomorphic phenomenology evolution until the present: first focal seizures with automatisms and right hemiconvulsions, later epileptic spasms and finally seizures with right eyes deviation and fencer's posture. The general examination was normal, with no dysmorphic features, and neurological evaluation only detected cognitive handicap. The sequential electroencephalografic analysis showed distinct ictal and interictal patterns: initially localized to the anterocentral bilateral regions with burst-suppression pattern, later on both anterolateral regions with subsequent progression to a predominantly bilateral posterior epileptiforme activity, and finally lateralized to the anterior left region. Investigation excluded metabolic and exclusively structural brain diseases, but functional imaging with PET revealed parietal hypometabolism, more pronounced on the right. The extensive genetic analysis revealed presence of deletions in the genes STXBP1 (9q34.11) and MACROD2 (20p12.2). Despite initial refractory, she is now seizure free on carbamazepine and vigabatrin. Conclusion: The case described above is a particular example of presentation of an early epileptic encephalopathy that is believed to be primarily associated with STXBP1 disruption. We discuss the contribution of additional gene MACROD2 deletion to the epileptic phenotype.
p144 TARGETED NEXT GENERATION SEQUENCING AS DIAGNOSTIC TOOL IN EPILEPTIC DISORDERS J. Lemke*, E. Riesch, T. Dorn, Y. Weber, H. Lerche, D. Bhm, and S. Biskup *University Children's Hospital, Bern, Switzerland; CeGaT GmbH, Tbingen, Germany; Swiss Epilepsy Center, Zrich, Switzerland; and University of Tbingen, Tbingen, Germany
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p146 ANALYSIS OF COPY NUMBER VARIATIONS AFFECTION ION CHANNEL GENES IN IDIOPATHIC GENERALIZED EPILEPSY -A CASE-CONTROL SURVEY USING A CUSTOMIZED MICROARRAY-BASED COMPARATIVE GENOMIC HYBRIDIZATION (IONCHANNEL ARRAY) P. Striano*, R. Paravidino*, M. Pezzella*, G. Giudizioso*, M. Montera*, A. Bianchi, A. Coppola, F. Dagna Bricarelli, D. A. Coviello, C. Minetti*, and F. Zara* *Gaslini Institute, University of Genova, Genova, Italy; Arezzo, Italy; Institute of Neurology, University College London, London, UK; and Galliera, Genova, Italy
Purpose: To perform an extensive search for genomic rearrangements (CNVs) involving ion channel genes in patients with idiopathic generalized epilepsy (IGE) by custom microarray-based comparative genomic hybridization (custom array-CGH). Method: Probands with familial (i.e., at least two first-degree or three affected relatives) IGE (classified according to the ILAE classification, 1989) and 110 healthy controls were screened by custom CGH-array designed to identify small CNVs affecting 429 candidate epileptogenic genes. This IonChannel array Agilent platform has 60.000 probes at the minimum resolution of 100 bp in exons and of 1000 bp in introns. Segregation analysis will be also performed. Result: One-hundred twenty probands from familial IGE and 110 healthy controls have been. CNVs involving ion channel genes were identified in both patients (mean size 412 Kb) and controls (mean size 354 Kb). In patients, we identified chromosomal microrearrangements involving different epilepsy candidate genes, including GABRG2, GABRAA1/A4, SCN1B, KCNE1/2, KCND2, TRPV2. Segregation analysis is ongoing for many cases but intragenic CNVs affecting GABRG2 and KCND2 were found in affected parents. Conclusion: IGE patients show a significantly increased burden of ion channel genes-rich CNVs. The identification of rearrangements affecting strong candidate epilepsy genes (e.g., GABRG2, KCND2) provides a compelling evidence that this method is a promising, powerful approach to improve dissection of complex pathogenesis of IGE. Result: Three polymorphisms in SCN1A, three in CACNA1A, and four in CACNA1B were identified in eight Japanese AHC patients. Of these polymorphisms, one in SCN1A, three in CACNA1A, and two in CACNA1B showed amino acid substitutions. Statistical examination showed no significant differences between healthy subjects and those with polymorphisms. Conclusion: Since AHC onset in our patients was within seven days after birth, we believe that AHC is caused by genetic abnormalities.
p148 GENETICS OF EPILEPSY, A DUTCH COHORT STUDY B. Berghuis*, G. De Haan, B. Koeleman, J. W. Sander, and D. Lindhout *SEIN, Zwolle, The Netherlands; Stichting Epilepsie Instellingen Nederland (SEIN), Heemstede, The Netherlands; University Medical Center Utrecht, Utrecht, The Netherlands; UCL Institute of Neurology, London, UK; and University Medical Centre Utrecht, Utrecht, The Netherlands
Purpose: To identify genetic variants for disease susceptibility in epilepsy, genetic variants that contribute to refractoriness to antiepileptic medication and genetic variants involved in common side effects of antiepileptic medication. We hypothesize that carriers of genetic mutations that cause epilepsy present a distinct and recognizable clinical phenotype. Method: The studypopulation exist of patients attending our outpatient epilepsy clinics, with a firm diagnosis of epilepsy, regardless of type. Characteristics of the epilepsy, including types and frequency of seizures, neurophysiology, imaging and response to medication are documented for each patient. We plan to perform Next Generation Sequencing, Genome Wide Association Studies and Copy Number Variation analysis in search for genetic variants in genes already known to cause epilepsy in families, associated with hyponatriema caused by carbamazepine, associated with obestiy and valproate use and with influence on anti-epileptic drug metabolism and transport. Result: Inclusion of patients started September 2010. At the start of 2012 over 700 patients provided informed consent and their DNA was sampled. Clinical phenotype was described of 453 patients. 83%(n=375) of patients had a focal epilepsy, 12%(n=56) a generalized epilepsy, 5%(n=22) was not well defined. 34%(n=155) of the epilepsies were symptomatic. 82% of patients had ever used carbamazepine, oxcarbazine or both. We plan to test for genetic variation in vassopressin pathway genes that may contribute to hyponatriema induced by these drugs. Conclusion: The main outcome of this project will be a description of clinical factors correlated to specific genetic risk variation, to enable clinical guidelines for early diagnosis and personalized treatment.
p147 GENETIC ANALYSIS OF SPORADIC ALTERNATING HEMIPLEGIA OF CHILDHOOD A. Ishii*, Y. Saito, M. Sasaki, and S. Hirose* *Fukuoka University, Fukuoka, Japan; and National Center of Neurology and Psychiatry, Tokyo, Japan
Purpose: To find candidate genes for Alternating Hemiplegia of Childhood (AHC). AHC begins with abnormal eye movement at around 23 months of age; hemiplegia follows at about 67 months; and later, quadriplegia (Alternating distonia in children) appears. Convulsions begin around the age of six, often causing tonic-clonic seizures and tonic seizures. Ultimately, paralysis and the patient's resultant bed-ridden condition lead to severe intellectual disabilities. Blood and spinal fluid tests, MRI images, and EEGs give no indication of the disease. The genes responsible for AHC are unidentified and its molecular genesis remains unclear. Method: In eight Japanese AHC patients, we investigated the genetic abnormalities of four genes encording a1 subunit of voltage-gated sodium channel, a2 subunit of ATP-dependent Na/K pump, a1 subunit of P/Q-type voltage-dependent calcium channel and a1B subunit of P/Qtype voltage-dependent calcium channel respectively, SCN1A, ATP1A2, CACNA1A and CACNA1B genes.
p149 CLINICAL FEATURES OF EPILEPSY IN DENTATORUBRAL-PALLIDOLUYSIAN ATROPHY PATIENTS H. Nakano, M. Kinoshita, and H. Sawada National hospital of Utano, Kyoto-shi, Japan
Purpose: We assessed the clinical features in dentatorubral-pallidoluysian atrophy patients who had epileptic seizures. Method: We included 5 DRPLA patients from different families (5 men; mean age, 31.2 years) who had expanded CAG repeat in DRPLA gene and epileptic seizures. And analyzed their clinical features based on medical recording. Result: All patients had marked dementia and cerebellar ataxia. A patient could perform simple verbal communication but other 4 patients
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could utter only fragmented words or couldn't speak. The mean disease duration was 17.6 years. Three patients had positive family history. The mean onset age of epileptic seizure was 13.6 years. All patients had generalized tonic clonic seizures and 2 also had partial seizures. The frequency of generalized seizures was monthly in 2 patients and yearly in 1. Two patients had no seizure over 1 year. The frequency of myoclonus was daily in 3, and monthly in 1. One patient had no myoclonus. Electroencephalography showed generalized epileptiform discharges in 4 patients and both generalized and focal epileptiform discharges in 3. In 2 patients, localization of focal epileptiform discharges corresponded to seizure semiology. Number of antiepileptic drugs co-administered was 5 in 1 patient and 4 in 4. Conclusion: DRPLA is one of the primary disease which induces progressive myoclonus epilepsy whose seizures in young onset patients are intractable. Our data suggest that in some patients critical seizures may be controlled with co-administration of multiple drugs.
*University of Antwerp, Antwerp, Belgium; and University Hospital Gasthuisberg, Leuven, Belgium
Purpose: Determine frequency of recurrent reciprocal genomic rearrangements of 17q12 in generalized epilepsy with febrile seizures plus (GEFS+). Method: De novo copy number variations (CNV) and inherited genomic rearrangements have been recognized as causal variants and risk factors for a variety of diseases. So on, CNV analysis has become an established tool in clinical diagnostics. Molecular karyotyping was performed with the 180k Cytosure ISCA v2 array (OTG) in a proband of a four generation GEFS+ family with eight affected members. Multiplex Amplicon Quantification was used for segregation analysis of the findings and screening of a follow up cohort. Result: Initially a 2.12Mb microduplication of 17q12 was identified in a proband whom has febrile, myoclonic, tonic-clonic seizures, absences and intellectual disability (ID). Subsequent analysis showed clear co-segregation of the variant with the phenotype in four additional family members. The follow up screening of other families, patients and controls is on going. Conclusion: Recent findings revealed that recurrent reciprocal genomic rearrangements of 17q12 (both deletions and duplications) can be associated with a combination of all previously described symptoms. Our results confirm, however, that microduplications of 17q12 can be associated with a restricted phenotype consisting of ID and seizures but without renal disease or diabetes. Epileptic phenotypes are often poorly described but our family falls within the GEFS+ spectrum. The presence of ID could be a clue for CNV screening but is not a requirement as most affected family members had a normal intellect. It remains an intriguing question how these rearrangements can lead to specifically epilepsy.
p150 EFFECT OF CYP3A4*1G/*18/*19 AND CYP3A5*3 GENOTYPE ON SERUM CARBAMAZEPINE CONCENTRATIONS AT STEADY-STATE IN HAN CHINESE EPILEPTIC PATIENTS J. Wang, and Z. Hong Institution of Neurology, Shanghai, China
Purpose: The present study aimed to assess the distribution of the CYP3A4*18/*19/*1G and CYP3A5*3 genotype in Han Chinese epileptic patients with carbamazepine (CBZ)-therapy and their effect on serum CBZ concentrations at steady-state. Method: The serum concentrations of CBZ and the CYP3A4*18/*19/ *1G and CYP3A5*3 genotype was determined in 247 Han Chinese including 177 monotherapy patients and 70 valproate-add-on patients. Result: In total group, the mutations of CYP3A4*18/*19 were not found. And the normalized concentrations of CBZ (concentration/ (weightdose)) were 0.250.067lgkgd (mlg)-1 for CYP3A4*1G non-expressors (AA and AG allele) and 0.280.080lgkgd (mlg)-1 for CYP3A4*1G expressor (GG allele)(P=0.003). It was 0.230.060lgkgd (mlg)-1 for CYP3A5*3 expressors (AA and AG -1 allele) and 0.300.076lgkgd (mlg) for CYP3A5*3 non-expressors (GG allele)(P<0.0001). The similar result was found in monotherapy and add-on group with CYP3A5*3 genotype, but not in add-on group with CYP3A4*1G. In monotherapy group, the normalized concentrations of CBZ were 0.250.065 lgkgd (mlg)-1 for CYP3A4*1G non-expressors and 0.280.074 lgkgd (mlg)-1 for CYP3A4*1G expressor (P=0.001). It was 0.240.054lgkgd (mlg)-1 for CYP3A5*3 expressors (AA and AG allele) and 0.310.072lgkgd (mlg)-1 for CYP3A5*3 non-expressors (GG allele) (P<0.0001). In add-on group, the normalized concentrations of CBZ were 0.240.070 lgkgd (mlg)-1 for CYP3A4*1G non-expressors and 0.260.087 lgkgd (mlg)-1 for CYP3A4*1G expressor (P=0.257). It was 0.210.068lgkgd (mlg)-1 for CYP3A5*3 expressors (AA and AG allele) and 0.290.078lgkgd (mlg)-1 for CYP3A5*3 non-expressors (GG allele) (P<0.0001). Conclusion: In generally, the CYP3A4*1G, CYP3A5*3 genotype affected the CBZ concentrations in Han Chinese patients that the normalized concentrations of CBZ in patients with CYP3A4*1G expressor (GG allele) and CYP3A5*3 non-expressors (GG allele) was higher than AG and AA allele. And it is a factor that may contribute to inter-individual variability in CBZ disposition in Han Chinese epileptic patients.
p152 A RAT MODEL FOR LGI1-RELATED EPILEPSY S. Baulac*, S. Ishida, T. Mashimo, M. Boillot*, N. Fumoto, M. Kuwamura, Y. Ohno, A. Takizawa, T. Aoto, M. Ueda, A. Ikeda**, R. Takahashi, E. Leguern*, and T. Serikawa *ICM, Paris, France; Institute of Laboratory Animals, Kyoto, Japan; Veterinary Pathology, Saka, Japan; Laboratory of Pharmacology, Osaka, Japan; PhoenixBio Co. Ltd, Utsunomiya, Japan; and **Graduate School of Medicine, Kyoto University, Kyoto, Japan
Purpose: Mutations of the leucine-rich glioma-inactivated 1 (LGI1) gene cause autosomal-dominant partial epilepsy with auditory features also known as autosomal-dominant lateral temporal lobe epilepsy (ADLTE). Besides, immune-mediated disruption of LGI1 results in seizures and limbic encephalitis. We aimed to generate an animal model for Lgi1related epilepsies. Method: The ENU (N-ethyl-N-nitrosourea)-mutagenized F344/NSlc rat archive (KURMA: Kyoto University Rat Mutant Archive) of the NBRPRat project was screened for mutations in the Lgi1 gene. We recovered an Lgi1-targeted rat carrying a missense mutation (L385R). Result: We provided evidence that L385R mutation prevented secretion of Lgi1 protein in COS7 transfected cells. However, low abundance of L385R-Lgi1 protein was found in the brains and primary cultured neurons of Lgi1-mutant rats, suggesting that mutant protein is destabilized in vivo. Phenotype of homozygous and heterozygous L385R-Lgi1 mutant rats was investigated. Behavioral observations and intracranial electroencephalographic monitoring recapitulated several features of the human disease: homozygous L385R-Lgi1 mutant rats by P10 experienced early-onset spontaneous epileptic seizures, and died prematurely. Moreover, adult heterozygous L385R-Lgi1 rats exhibited markedly higher susceptibility to sound-induced seizures (generalized tonic-clonic seizures) compared
p151 RECURRENT RECIPROCAL GENOMIC REARRANGEMENT OF 17Q12 AS A CAUSE OF GEFS+ K. Hardies*, E. Peeters, A. Suls*, S. Weckhuysen*, P. Holmgren*, W. Van Paesschen, and P. De Jonghe*
46 Abstracts
to control animals. Audiogenic seizures were suppressed by the administration of several antiepileptic drugs (carbamazepine, phenytoin and levetiracetam) commonly used to treat partial seizures, but not by ethosuximide, a drug of choice for absence seizures. Conclusion: Our findings provide the first rat model harboring a missense mutation in the Lgi1 gene, yielding a complementary model to classical knockout mice to study Lgi1-related epilepsies. tion, EEG, ECG, and plasmatic levels of AED were performed before and after LCM treatment. The efficacy was calculated in relation to seizure frequency reduction using parents diaries. LCM dose ranged between 200 and 400 mg/die in young adult and 6 mg/kg/die in children. Result: The follow-up ranged from 4 to 18 months. At the end of the follow-up, seizure frequency reduction was of 75% in 9 patients (45%) of the group A and in 2 patients (28.5%) of the group B. In only 1 patient LCM was discontinued because of inefficacy. Diplopia, nausea and dizziness reported during the titration period in 11 patients of the group A disappeared reducing the associated sodium channel - blocking AED. Conclusion: LCM showed good tolerability in add on in pediatric population. Despite the small sample of the group B, our preliminary data suggested that LCM seems more efficacy in reducing seizure frequency in patients with refractory focal epilepsy treated with concomitant traditional sodium channel- blocking AED.
p153 EPILEPSY ASSOCIATED WITH 22Q11.21 MICRODUPLICATION S. Tang*, E. Hughes, and D. K. Pal* *King's College London, London, UK; and King's Health Partners, London, UK
Purpose: Epilepsy is a little known association in 22q11.21 duplication. Here we describe the phenotype of affected children from two large databases of genomic variation. Method: After finding an index affected child, we searched the clinical genetics database [http://bbgre-dev.iop.kcl.ac.uk] of 10,397 individuals, as well as DECIPHER database. Result: The index child carried a de novo 2.49MB duplication of 22q11.21 (between LCR22B and LCR22E) as well as a maternally inherited 15kB microdeletion of chromosome 2p16.3 in an intronic region of neurexin-1. He presented age five with atypical benign partial epilepsy with left centro-temporo-parietal discharges, focal atonic seizures progressing to ESES. He also had some autistic spectrum, attentional and memory difficulties but no MRI evidence of malformation. Both parents were asymptomatic. In BBGRE we found 30 other individuals with 22q11.21 duplications: 19 had developmental delay; 8 had autism spectrum disorders; 17 had dysmorphism or congenital malformations; and only one other individual had epilepsy (infantile spasms). In DECIPHER, we identified 73 individuals with 22q11 duplication and variable phenotypes of whom only two were reported to have epilepsy with no further details. In the literature, five children with 22q11.21 dup have been reported with epilepsy or abnormal EEG and a variety of other features: one with nocturnal focal seizures and waking state epileptic spasms (Shimojima, 2010); another with occipital epilepsy and polymicrogyria in a child with co-existing inverted 9p dup/del (Mosca, 2009). Conclusion: The 22q11.21 duplication is associated with a variable phenotype; epilepsy is an uncommon association and both focal nocturnal seizures and epileptic spasms are specific findings.
p155 COST UTILITY ANALYSIS OF PHENOBARBITAL AS MONOTHERAPY AMONG ADULT EPILEPSY PATIENTS IN A TERTIARY HOSPITAL P. P. Pingul Philippine Neurological Association, Quezon City, Philippines
Purpose: To evaluate the cost-utility profile of Phenobarbital as monotherapy among adult epilepsy patients in a tertiary hospital. Method: Adult epilepsy patients receiving Phenobarbital for at least a year, consenting and capable of answering the questionnaire were included in the study. The overall costs of treating epilepsy in this population in terms of the direct costs (visits, hospitalizations, diagnostics, treatment, transportation, nursing care) and indirect costs (employmentrelated losses) were determined. Outcome measures were described in this study as seizure frequency, patient satisfaction, adverse symptoms, and quality-of-life measurement using a multiattribute utility scale to derive QALYs (quality adjusted life years). Result: Monotherapy with Phenobarbital has shown high efficacy with 77% of patients experiencing a seizure attack of only once every 2 months or less. Tolerability is also good as 84% of the population expressed satisfaction with the drug despite 41% experiencing side effects of drowsiness and forgetfulness. Overall health state preference of 0.78 using the HUI-III among these patients on Phenobarbital is comparable to those with self-reported epilepsy from other studies. The overall cost of treating epilepsy with Phenobarbital per patient per year was Php 5, 255.62. The overall gain in health as expressed in QALYs per patient was 41.80, and the cost per QALY gained was Php 124.33. Conclusion: Phenobarbital monotherapy among adult epilepsy patients has shown overall favorable results, particularly in terms of cost per quality adjusted life years gained, with reference to current pharmacoeconomic standards.
Medical Therapy and Pharmacology 1 Monday, 01 October 2012

p154 LACOSAMIDE IN ADD-ON IN CHILDREN AND YOUNG ADULTS AFFECTED BY DRUG-RESISTANT EPILEPSY D. Battaglia, C. Brogna, I. Contaldo, F. Perrino, E. Albamonte, E. Losito, S. Veltri, G. Leo, D. Ranalli, and D. Lettori Catholic University, Rome, Italy
Purpose: To evaluate efficacy and tolerability of LCM in add-on with traditional sodium channel - blocking AED [SCB (+)] and other AED [SCB (-)] in children and young adults with drug-resistant epilepsy Method: 27 patients, aged between 3 and 31 years, affected by refractory epilepsy, were enrolled and divided in 2 groups: 20 patients treated by LCM in add on with SCB (+) (group A), and 7 patients treated by LCM in add on with SCB (-) (group B). Epilepsy type consisting of symptomatic (23) and presumed symptomatic (3) focal epilepsy. Neurological examinaEpilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x
p156 EFFECTS OF VALPROIC ACID TREATMENT IN LIPID PROFILE AND HS-CRP IN EPILEPTIC PATIENTS S. Markoula*, D. Chatzistefanidis*, C. Tzallas, G. Lagos*, E. Bairaktari, and A. P. Kyritsis* *University of Ioannina, Ioannina, Greece; and University Hospital of Ioannina, Ioannina, Greece
Purpose: To investigate the role of daily dose, valproate's blood level and treatment duration in lipid profile alterations and HS-CRP blood level of epileptic patients receiving valproic acid. Method: Epileptic patients receiving valproic acid were consecutively recruited. Sex, age, daily dose and duration of treatment were recorded.
47 Abstracts
Waist perimeter, weight and height were measured. Fasting blood samples were collected to measure triglycerides, LDL, HDL, total cholesterol and valproic acid along with HS-CRP blood level. Result: Forty-six patients (29 males and 17 females) were included. Mean age was 39.5 years (males 41.2 years, females 36.6 years). Daily dose level was not related to BMI, waist perimeter, total cholesterol, triglyceride, LDL or HDL level. Treatment duration over 24 months was related to a significant increase in BMI and total cholesterol level (p < 0.05), as well as LDL level (p=0.057). This effect was statistically significant only in men, although women showed a similar trend. HS-CRP blood level was positively related to drug's daily dose and blood level. Conclusion: Alterations in lipid profile and body weight are mainly a result of treatment duration. On the other hand, HS-CRP blood level was positively influenced by daily dose and drug blood level. This knowledge is important when deciding the daily dose and treatment duration in patients with metabolic syndrome and/or evidence of cardiovascular disease. seizure type and number of concomitant antiepileptic drugs (AEDs) were summarized for the three studies. Result: 388, 386 and 706 patients were included in the safety population in studies 304, 305 and 306, respectively. Mean age was similar in each study (36.0, 35.5 and 33.8 years for 304, 305, 306, respectively); 8.5 11.4% of patients were aged <18 years. Approximately half of patients were female: 51.5%, 51.8% and 51.1%. The majority of patients were white (>65.0%); however, study 306 had a higher proportion of Asian/ Chinese patients (34.6%) compared with 304 or 305 (1% and 10.9%, respectively). Mean time since diagnosis was 23.7, 22.0 and 19.1 years. At Baseline, simple partial seizures (without motor signs) occurred in 36.9%, 34.5%, 29.7% of patients in 304, 305 and 306, respectively; simple partial seizures (with motor signs) occurred in 33.0%, 27.7%, 30.2%; complex partial seizures occurred in 88.9%, 85.0%, 84.0%; and complex partial plus secondary generalization occurred in 71.9%, 67.9%, 69.0%. The mean number of AEDs received in the past 5 years was 2.8, 3.2 and 3.4 for patients entering 304, 305 and 306, respectively. Conclusion: Patient populations in the three phase III trials of adjunctive perampanel for treatment of refractory partial-onset seizures were similar. Support: Eisai Inc.
p157 RECTAL CARBAMAZEPINE AS EFFECTIVE TREATMENT FOR ESCALATING SEIZURES AND STATUS EPILEPTICUS D. J. Cordato*, V. I. Patel*, and R. G. Beran *Liverpool Hospital, Liverpool, NSW, Australia; and Griffith University, South Port, Qld, Australia
Purpose: Carbamazepine (CBZ) is the gold standard anti-epileptic drug (AED) for focal onset seizures. The aim of this study is to examine the potential use of rectal (PR) CBZ as an alternative to parenteral AEDs in status epilepticus (SE) or cluster seizures. Method: Oral CBZ syrup was given PR using 400mg equivalent aliquots. Serum CBZ levels were requested 30 to 60 minutes after administration to confirm absorption and achievement of minimum therapeutic levels (total CBZ > 20 lmol L-1). Where levels were sub-therapeutic, the procedure was repeated using 400mg CBZ bolus aliquots until therapeutic levels were achieved. Result: 6 patients received PR CBZ, to manage cluster seizures following initial treatment with IV benzodiazepines. All patients seizures ceased and therapeutic CBZ levels were achieved in 5 of 6 subjects with 510 hours of initial CBZ dosing. Conclusion: PR CBZ is a viable alternative to parenteral AEDs in patients presenting with SE or cluster seizures.
p159 EFFICACY AND SAFETY OF LACOSAMIDE AS ADJUNCTIVE THERAPY IN A COHORT OF CHILDREN WITH REFRACTORY PARTIAL-ONSET EPILEPSY J. Kaleyias, A. Koukouletsos, A. Frimas, E. Tsekoura, A. Anagnostopoulou, A. Varvarigou, and S. Mantagos University Hospital of Patras, Patra, Greece
Purpose: To evaluate the efficacy and safety of lacosamide (LCM) as adjunctive treatment in a cohort of children with uncontrolled partialonset seizures taking one to three concomitant AEDs (Guilhoto LM et al. Pediatr Neurol 2011; 44: 414419). Method: Retrospective review of charts identified 14 children (11 males, mean age 10.7 years, range 4.517) with refractory partial-onset seizures on LCM. Seizure count and side effect (SE) profile were maintained during therapy. Good responders were defined those with 50% seizure frequency reduction. Statistical analysis was performed with SPSS. Result: Causes of epilepsy included tuberous sclerosis complex (n=3), Rett (n=1), Aicardi (n=1), Sotos syndrome (n=1) and CP (n=2). The median age of seizures onset was 2 years (Intraquartile range: IQR 15), median length of follow-up 7 years (IQR 210) and the median duration on LCM was 23 months (range 348). The median number of AEDs before LCM was 7 (range 210). LCM dosage was 5 mg/k/d (range 310). Good responders were 50% (7/14) [(2/14 (14%)] became seizure-free and currently in LCM monotherapy). In 7 children (50%) LCM had to be discontinued: 4 (28%) due to poor seizure control and 3 (21%) due to SEs and marginal benefit. The mean number of previous AEDs in responders was 4.4 while in non-responders was 8 (p <0.008). SEs were reported in 57% (8/14) (nausea, dizziness, somnolence, irritability, agitation); 3/14 side effects prompted LCM discontinuation [persistent somnolence (n=2), agitation (n=1)]. Conclusion: Lacosamide was demonstrated to be effective and safe in this cohort of children with refractory partial-onset seizures.
p158 PHASE III TRIALS OF ADJUNCTIVE PERAMPANEL, A SELECTIVE AMPA RECEPTOR ANTAGONIST, IN PATIENTS WITH TREATMENT-RESISTANT PARTIALONSET SEIZURES: ANALYSIS OF PATIENT DEMOGRAPHICS AND BASELINE CLINICAL CHARACTERISTICS V. Villanueva*, G. L. Krauss, C. Brandt, D. Squillacote, H. Yang, D. Kumar, and A. Laurenza *Hospital Universitario y Politcnico La Fe, Valencia, Spain; Johns Hopkins University, Baltimore, MD, USA; Bethel Epilepsy Centre, Mara Hospital, Bielefeld, Germany; and Eisai Neuroscience Product Creation Unit, Woodcliff Lake, NJ, USA
Purpose: To describe demographics and baseline characteristics of patients in three phase III trials of adjunctive perampanel for treatmentresistant partial-onset seizures (studies 304, 305, 306). Method: Patients were randomized to once-daily placebo, perampanel 2 mg, 4 mg, 8 mg or 12 mg. Patient demographics, time since diagnosis,
p160 THE EFFECTS OF ESLICARBAZEPINE AND R-LICARBAZEPINE ON SODIUM CURRENTS THROUGH NAV1.7 AND NAV1.8 CHANNELS S. Hebeisen*, K. Brady*, and P. Soares-Da-Silva
48 Abstracts
*BSYS GmbH, Witterswil, Switzerland; and University of Porto, Porto, Portugal
Purpose: Eslicarbazepine is the major active metabolite of eslicarbazepine acetate, a once-daily antiepileptic drug approved in Europe as adjunctive therapy for refractory partial-onset seizures in adults. This study was aimed to determine the effects of eslicarbazepine and R-licarbazepine on the human NaV1.7 and NaV1.8 sodium channels expressed in CHO cells. Method: About 2448 hours following transfection with human NaV1.7 cDNA or NaV1.8 cDNA, cells were ready for electrophysiological experiments. The whole-cell patch-clamp technique was used to investigate the effects of eslicarbazepine and R-licarbazepine on NaV1.7 and NaV1.8 inward peak currents. Compounds were tested at -80 mV holding potential. The affinity for the resting (KR) and inactivated (KI) states was examined after 15 s conditioning pre-pulses ranging from -120 mV to -40 mV. Result: At -80 mV holding potential, eslicarbazepine and R-licarbazepine were equipotent in inhibiting inward sodium currents through NaV1.7 and NaV1.8 channels. However, the affinity of eslicarbazepine for the inactivated (KI) state of Nav1.7 and Nav1.8 channels was 10 to 2 times higher than that for R-licarbazepine. On the other hand, both compounds demonstrated a 10- to 5-times higher affinity for the inactivated (KI) state versus the resting (KR) state of the NaV1.7 channels, when compared to NaV1.8 channels. Conclusion: Eslicarbazepine is endowed with a greater selectivity for the inactive state of NaV1.7 and NaV1.8 sodium channels, when compared with R-licarbazepine.
p162 EFFICACY OF INTRAVENOUS LACOSAMIDE IN PATIENTS WITH CONVULSIVE VERSUS NON-CONVULSIVE STATUS EPILEPTICUS E. Y. Moreno, M. Peleterio, E. Bondy, J. Domnguez, E. Pardellas, and A. Fernandez University Hospital of Santiago de Compostela, Santiago de Compostela, Spain
Purpose: To compare the efficacy of intravenous lacosamide in patients with convulsive versus non-convulsive status epilepticus. Method: In this prospective, observational study, patients with convulsive or non-convulsive SE that received iv lacosamide 200400 mg iv for 8 days were compared for electroencephalographic response and seizure termination. Result: Among 53 patients treated with iv lacosamide (mean dose 390.6 mg for 8 days) as first- (34%) or second-line (66%) treatment for convulsive (43.4%) or non-convulsive (56.6%) SE, the mean age was 55.2 years and 13.2% had prior epilepsy. The majority (73.6%) of patients had a comorbid condition, predominantly hypertension (35.8%) and head injury (11.3%). The majority (79.2%) of patients received concomitant antiepileptic drugs, either 1 (34%), 2 (22.6%) or 3 (22.6%) agents, including midazolam (54.7%), valproic acid (52.8%), and levetiracetam (30.2%) The other AEDs were used in principle to stop the SE but the patients did not respond and so we used lacosamide, however there are some exceptions in whichinput was used. EEG confirmation of improvement following lacosamide treatment was very positive in 56.6% of patients; 69.6% of the convulsive and 46.7% of the non-convulsive SE groups. Among all patients, 90.6% showed clinical improvement and there was no significant between-group difference for achievement of seizure termination, 90% and 91.3% of the non-convulsive and convulsive SE groups, respectively. There were no reports of adverse events Conclusion: Intravenous lacosamide was safe and similarly effective in patients with convulsive or non-convulsive SE . Further investigation into the use of lacosamide in the treatment of SE is warranted.
p161 SYMPTOMS AND COURSE OF INTOXICATION WITH MESUXIMIDE C. Brandt*, R. Hoepner, B. Rambeck, H. Ottenottebrock*, and T. W. May *Bethel Epilepsy Centre, Bielefeld, Germany; St. Josef Hospital, Bochum, Germany; and Society for Epilepsy research, Bielefeld, Germany
Purpose: We report on a patient who presented with somnolence due to intoxication by the antiepileptic drug (AED) mesuximide (MSM). The purpose is to highlight the symptoms and treatment of MSM intoxication and thus to raise awareness for a severe, but treatable condition in association with an AED that is used quite rarely nowadays. Method: Case report. Result: This 31-year-old, mentally impaired female patient suffered from cryptogenic focal epilepsy with complex-partial and secondarily generalized tonic-clonic seizures since the age of twelve. She was admitted to a local hospital because of frequent falls supposed to be of epileptic origin. Primidone 62.5 mg was added. When she was transferred to our hospital, she was somnolent, vomited and responded undirectedly to painful stimuli. AED serum concentrations were as follows: Valproic acid 70.9 mg/L (reference range 40100 mg/L), lamotrigine 8.1 mg/L (2 10 mg/L), n-desmethyl-mesuximide (NDM) 85.7 mg/L (1040 mg/L). MSM was withdrawn, and she was treated by hemodialysis. After the first course of hemodialysis NDM serum concentration had decreased, and the patient was awake and responsive. Conclusion: In somnolent patients treated with MSM and NDM levels above the therapeutic range (1030 mg/L), drug intoxication here probably chronic with a vicious circle of loss of appetite, add-on of primidone and subsequent further increase of serum concentrations should be considered, adequate treatment initiated. Due to the rare use of MSM it is even more important to know the symptoms of intoxication in order not to miss a potentially life-threatening, treatable condition.
p163 RESPONSE TO ADD-ON LACOSAMIDE IN PATIENTS WITH REFRACTORY EPILEPSY J. Rodrguez Uranga Instituto de Especialidades Neurolgicas (IENSA), Sevilla, Spain
Purpose: Evaluate the efficacy and safety of adjunctive lacosamide in patients with refractory epilepsy receiving up to 3 other antiepileptic drugs. Method: In this retrospective, observational, non-interventional, postauthorization study, patients with partial-onset seizures receiving 13 AEDs received adjunctive lacosamide with doses from 100 to 400 mg (with a mean of 249.2 mg) for up to 5 months. Change in seizure frequency from pre- to post-treatment was assessed using the McNemar's test of change. Result: Sixty four patients of mean age 38.4 years with a median history of epilepsy of 2 (15) months received add-on oral lacosamide (mean dose 249.2 [100400] mg/day) for a mean of 2.6 months. Most patients had complex partial (34.4%), or complex (15.6%) or simple (9.4%) partial with secondary generalization subtype of epilepsy. For patients receiving 1, 2 or 3 AEDs, lacosamide was add-on treatment in 15 (23.4%), 36 (56.3%) and 13 (20.3%), respectively. AEDs most commonly used included levetiracetam (39.1%), carbamazepine (35.9), valproic acid (32.8%), lamotrigine (25%), and oxcarbazepine (20.3%). Initially, 63 patients (98.4%) had a seizure; by study end, this was reduced to 47 (73.4%). Among the patients with baseline seizures, 25%
49 Abstracts
had no seizures at end of treatment, a statistically significant reduction (p < 0.001). Median percentage reduction in seizure frequency was 56.7%. The response rate was 66.7% (seizure free [27%], reduction in seizure frequency 50% [39.7%]), 15.9% had a reduction <50%, 17.5% had no change in seizure frequency. Conclusion: Add-on lacosamide was safe and effective in a broad range of patients with refractory epilepsy receiving 13 AEDs.

p165 ZONISAMIDE MONOTHERAPY IN ADULT PATIENTS WITH PARTIAL, GENERALIZED & COMBINED SEIZURES: FINDINGS OF A OPEN-LABEL, NON-COMPARATIVE, OBSERVATIONAL STUDY A. Dash*, S. C. Mehta*, N. C. Manjunath, A. Kiran, B. Jyothi, V. Bajpai, V. N. Mathur**, S. Shah, and D. Langade *Eisai Pharmaceuticals India Private Limited, Mumbai, India; Brain & Nerve Care Centre, Bangalore, India; Ayush Neuro Care, Secunderabad, India; Mediplus Clinic, Hyderabad, India; Sai Neurology Clinic, Lucknow, India; **Vivekananda Hospital, Hyderabad, India; Advanced Neurology & Superspecilaity hospital, Jaipur, India; and Institute of Medical Science & Research, Faridabad, India
Purpose: To evaluate efficacy and safety of Zonisamide monotherapy in adult patients with partial, generalized & combined seizures. Method: In this open, non-comparative, multi-center, observational study, 59 patients (36 males, 23 females) having partial, generalized and combined seizures were treated with Zonisamide monotherapy (100 500mg/day) for 24 weeks. Seizure frequency, clinician's global assessment of response to therapy (CGART) and patient's global assessment of tolerability to therapy (PGATT) were assessed every 4 weeks. Primary outcome was reduction in seizure frequency and secondary outcomes were responder rate (50% reduction in seizure frequency) and seizure freedom over 24 weeks. Adverse events were recorded during the study period. Change in seizure frequency from baseline was analyzed by Friedman test (non-parametric repeat measures ANOVA). Result: Fifty one patients completed 24 weeks study period, and 8 did not complete the study (4 lost to follow up, 3 due to medication error, and 1 withdrew due to adverse event). Mean percent reduction in seizure frequency at 24 weeks was 78.02% (95% CI 61.75131.02). After 24 weeks, the responder rate was 74.29% (26/35), whereas 24 weeks seizure freedom was 22.86% (8/35). Adverse events were reported in 3 (5.08%) patients, of which 1 (1.69%) patient each reported loss of appetite, dizziness, and aggressive behavior with sleep disturbance. Patient reporting aggressive behavior with sleep disturbance withdrew from the study. Conclusion: Zonisamide monotherapy demonstrates favorable efficacy and tolerability in adult patients with partial, generalized & combined seizures, however small sample limits the generalization of the findings.
p164 LEVETIRACETAM IS SUPERIOR TO CARBAMAZEPINE-SR IN NEWLY DIAGNOSED EPILEPSY IN THE ELDERLY: RESULTS OF THE STEP-ONE TRIAL K. J. Werhahn*, E. Trinka, J. Dobesberger, C. Ruckes, and G. Krmer *University Medical Center of the Johannes Gutenberg University, Mainz, Germany; Paracelsus Medical University, Salzburg, Austria; University Medical Center Mainz, Mainz, Germany; and Swiss Epilepsy Centre, Zurich, Switzerland
Purpose: Rationale: A multicentre, double-blind, randomized, head-tohead comparison of levetiracetam (LEV), slow-release carbamazepine (CBZ-SR), and lamotrigine (LTG) in newly diagnosed elderly patients with focal epilepsy (Study on the Treatment of Elderly Patients with Older and Newer antiepileptic drugs; NCT00438451; EudraCT Number: 2005-003324-19). Method: Patients aged 60 years or above with new onset focal epilepsy (either at least one seizure and spike discharges on EEG or a relevant lesion on CT/MRI or a total of 2 spontaneous seizures) were eligible; those with symptomatic epileptic seizures due to acute (< 2 weeks) cerebral lesions were excluded. Patients received LEV, CBZ-SR, or LTG (initial target dose of 1000mg LEV, 400mg CBZ-SR, or 100mg LTG) in a parallel group design over 58 weeks (6 weeks titration and 52 weeks maintenance). Following titration patients were treated individually in a double-blind manner depending on efficacy and tolerability on doses between 500 3000mg for LEV, 200 1200mg for CBZ-SR, or 50 300mg for LTG. Result: A total of n=361 patients were randomized and n=359 included in the intention-to-treat (ITT) population. Mean (SD) age was 71.8 7.5 for LEV (n=122, 34% female), 71.7 6.7 for CBZ-SR (n=120, 46%), and 70.7 7.4 for LTG (n=117, 41%). The mean number of seizures prior randomization were 3.8 9.9, 4.8 10.8, and 2.7 3.1 for LEV, CBZ-SR, and LTG respectively (p < 0.05 for CBZ-SR vs. LTG, t-test). Based on the ITT population retention rates at 58 weeks (primary endpoint) were 61% (95%CI: 5370) for LEV, 46% (95%CI: 3755) for CBZ-SR, and 56% for LTG (95%CI: 4765) [pvalues: overall 0.048; LEV vs. CBZ-SR 0.02, LEV vs. LTG 0.36, LTG vs. CBZ-SR 0.15, Fisher exact test]. Logistic regression revealed an odds ratio (OR) for a retention to treatment at 58 weeks of 1.838 (95%CI: 1.0923.093) for LEV vs. CBZ-SR, of 1.169 (95%CI: 0.689 1.984) for LEV vs. LTG, and of 0.636 (95%CI: 0.3771.073) for CBZ-SR vs. LTG. The number of concomitant diseases significantly influenced 58-week retention (OR 0.921; 95%CI 0.8590.987), i.e. chances to remain on therapy were reduced by 7.9% with each additional concurrent disease. There were no significant differences in seizure-freedom rates at week 30 (LEV 48%, CBZ-SR 39%, LTG 49%) and 58 (LEV: 43%, CBZ-SR 33%, LTG 38%) and in time-to-first seizure from randomization or after titration (after week 6). Conclusion: Results demonstrate evidence of superiority of LEV in monotherapy to CBZ-SR in new-onset focal epilepsy in the elderly. As the trial was not powered for the comparison of LEV and LTG there was no significant difference between these treatment arms. However, results do suggest that LEV should be among the first-line treatments in newonset epilepsy of the elderly population. Future head-to-head trials with novel or other antiepileptic drugs in the elderly population need to consider LEV as comparator.
p166 PHASE III, DOUBLE-BLIND, RANDOMISED, PLACEBO-CONTROLLED TRIAL ASSESSING EFFICACY AND SAFETY OF ADJUNCTIVE ZONISAMIDE THERAPY IN PAEDIATRIC PATIENTS WITH PARTIALONSET SEIZURES: PRELIMINARY ANALYSIS OF EFFECTS ON COGNITION A. Rosati*, J. Segieth, L. Giorgi, and R. Guerrini* *Children's Hospital Anna Meyer-University of Florence, Florence, Italy; and Eisai Limited, Hatfield, UK
Purpose: Zonisamide is currently licensed for adjunctive treatment of adults with partial seizures (with or without secondary generalisation). A Phase III trial recently assessed the efficacy/safety of adjunctive zonisamide in paediatric patients with partial epilepsy. Presented here are preliminary results of assessments of cognition that were included in the trial.
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Method: Paediatric patients (617 years) with partial epilepsy received adjunctive zonisamide 8 mg/kg/day (N=107) or placebo (N=100) for 20 weeks (8 weeks titration, 12 weeks maintenance) in a Phase III trial. Effects on cognition (including power of attention, continuity of attention, quality of working memory, speed of memory, and picture recognition sensitivity index) were assessed in around 80 patients with intelligence quotient 75. Last observation carried forward (LOCF) and observed case data were analysed using analysis of covariance. Result: No treatment effect was observed on power of attention (primary variable), continuity of attention, quality of working memory, and picture recognition sensitivity index (p>0.05 for all). Some evidence of impairment with zonisamide was observed on speed of memory at final visit, but only for the LOCF analysis using reciprocal transformed raw data (p=0.0275). Conclusion: No significant effects on psychomotor/information processing speed, attention (focussed and sustained), working memory (verbal and visuo-spatial), or episodic memory (visual recognition) were observed following 20 weeks treatment with adjunctive zonisamide in paediatric patients with partial epilepsy. Supported by Eisai
*Eisai Pharmaceuticals India Private Limited, Mumbai, India; Advanced Neurology & Superspecilaity hospital, Jaipur, India; Vivekananda Hospital, Hyderabad, India; Brain & Nerve Care Centre, Bangalore, India; Mediplus Clinic, Hyderabad; **Caring Hands Neuro Centre, Vishakhapatnam, India; Metro Hospital & Heart Institure, Noida; Sai Neurology Clinic, Lucknow, Indonesia; Institute of Medical Science & Research, Faridabad, India; and 1. Eisai Pharmaceuticals India Private Limited, Mumbai, Mumbai, India
Purpose: To evaluate efficacy and safety of Zonisamide in adult patients with partial, generalized & combined seizures. Method: In this open, non-comparative, multi-center, observational study, 113 patients (65 males, 48 females) having partial, generalized and combined seizures were treated with Zonisamide (100500mg/day) for 24 weeks as first add-on to the primary antiepileptic drug of clinician's choice. Seizure frequency, clinician's global assessment of response to therapy (CGART) and patient's global assessment of tolerability to therapy (PGATT) were assessed every 4 weeks. Primary outcome was reduction in seizure frequency and secondary outcomes were responder rate (50% reduction in seizure frequency) and seizure freedom over 24 weeks. Adverse events were recorded during the study period. Change in seizure frequency from baseline was analyzed by Friedman test (nonparametric repeat measures ANOVA). Result: Eighty five patients completed 24 weeks study period, and 28 did not complete the study (20 lost to follow up, 7 due to medication error, and 1 withdrew due to adverse event). Mean percent reduction in seizure frequency at 24 weeks was 71.21% (95% CI 57.94103.88). After 24 weeks, the responder rate was 76.81% (53/69), whereas 24 weeks seizure freedom was 30.88% (21/68). Adverse events were reported in 4 (3.54%) patients, of which 2 (1.77%) patients reported loss of appetite and one had weight loss (0.88%) during study. One (0.88%) patient was withdrawn from the study due toincrease in seizure frequency. Conclusion: Zonisamide demonstrates favorable efficacy and tolerability as first add-on in adult patients with partial, generalized & combined seizures.
p167 SEXUAL HORMONAL PROFILE OF EPILEPTIC MALE PATIENTS RECEIVING VALPROIC ACID D. Chatzistefanidis*, S. Markoula*, A. Giaka*, C. Tzallas, E. Bairaktari, and A. P. Kyritsis* *University of Ioannina, Ioannina, Greece; and University Hospital of Ioannina, Ioannina, Greece
Purpose: To study the impact of daily dose level and duration of treatment on hormonal profile of male epileptic patients receiving valproic acid. Method: Male patients receiving valproic acid and hospitalized in the Department of Neurology were consecutively recruited. Age, daily dose and duration of treatment were recorded. Blood samples were collected to measure testosterone, sex hormone-binding globulin (SHBG), FSH and LH blood levels. Result: Twenty six patients (mean age 37.9 years) were enrolled in our study. Testosterone level was significantly higher in patients receiving valproic acid doses of more than 2000 mg (mean testosterone value of 7.2 ng/ml versus 4.1 ng/ml, p < 0.05). Additionally, FSH (2.8 IU/l vs 4.1 IU/ l) and LH (2.8 IU/l vs 3.8 IU/l) blood levels were lower, while SHBG blood level was higher (62.3nmol/l vs 38.5 nmol/l) in patients receiving doses higher than 2000 mg, although these differences didn't reach statistical significance. Regarding treatment duration, none of the differences reached statistical significance, although there was a trend of increased mean testosterone (5.3 ng/ml vs 4.1 mg/ml) and decreased LH blood levels (2.7 IU/l vs 4.5IU/l) when treatment duration was longer than 24 months. Conclusion: Testosterone blood level is significantly affected by a daily dose exceeding 2000 mg. There is a trend for higher SHBG and lower FSH and LH blood levels, which may result from negative feedback of testosterone, in patients receiving daily doses higher than 2000 mg. Treatment duration longer than 24 months caused a non-significant increase in patients mean testosterone and decrease in LH blood level.
p169 RETIGABINE - A CHALLENGE FOR THERAPEUTIC DRUG MONITORING U. Juerges, and B. J. Steinhoff Epilepsy Centre Kork, Kehl-Kork, Germany
Purpose: Retigabine (RTG) is a new antiepileptic drug that was approved and introduced in Germany in 2011. For most antiepilectic drug therapies drug monitoring has proved a useful and valuable tool. The special feature of retigabine is its excessive metabolization. The major metabolites are RTG-N-glucuronide and N-acetyl-RTG, where the Nglucuronide and RTG have a constant ratio of 25:1. Although we do not know what kind of anticonvulsive properties the metabolites have, it is helpful to quantify not only the active agent RTG, but the metabolites also. What method is suitable for analyzing retigabine and its metabolites in serum or plasma? Method: RTG is quantified with a mass spectrometric method. The sodium adducts are analyzed as target ions: RTG-Na ion=326; acetylRTG-Na ion=296. Chromatographic settings include: column: 150x4PerfectSil5lm, mobile phase: 1mM sodium acetate/methanol isocratic. Sample preparation via methanol precipitation and dilution of extract with sodium acetate solution (0.2%). Internal standard. Result: The quantification of RTG as sodium adduct allows a selective and sensitive analysis of RTG and the metabolite N-acetyl-RTG. Using a pH neutral mobile phase and excluding all acidic additives allows to represent the in vivo metabolite distribution. Solutions of pH < 6 lead to the decomposition of N-glucuronide and so to falsely increased retigabine
p168 EFFICACY AND SAFETY OF ZONISAMIDE AS FIRST ADD-ON THERAPY IN ADULT PATIENTS WITH PARTIAL, GENERALIZED & COMBINED SEIZURES S. C. Mehta*, S. Shah, V. N. Mathur, N. C. Manjunath, B. Jyothi, B. Demudubabu**, V. Kumar, V. Bajpai, D. Langade, and A. Dash
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values. To obtain stable sodium adducts for RTG and N-acetyl-RTG an excess of sodium ions is needed. Conclusion: RTG drug monitoring via a selective and sensitive analysis method is possible using mass spectrometry. The analysis as sodium adduct in a pH neutral solution with sodium ion excess is recommended. reduction in countable seizures and 6 had a 2550% seizure reduction, while seizure frequency remained unchanged in 6. 9/14 responders had a reduction in drop attack and 6/14 patients had 50% decrease in seizures. 11/24 patients reported mild adverse effects. 5 of 24 patients discontinued the treatment after 35 months because of serious adverse events. 19 remaining patients were observed for mean period of 44.5 weeks. Efficacy on seizure frequency remained steady until the end of the study. Cognitive and adaptive assessments reperformed after 12 months of rufinamide treatment showed that 19/24 patients didn't have a change in IQ and adaptive behaviour score. Conclusion: Our data suggest that rufinamide may be effective and well tolerated in the treatment of young patients with LGS. Moreover rufinamide treatment was associated with low incidence of cognitive and psychiatric adverse events.
p170 EFFECTS OF ESLICARBAZEPINE, R-LICARBAZEPINE AND OXCARBAZEPINE ON FAST AND SLOW INACTIVATION OF VOLTAGE-GATED SODIUM CHANNELS C. Aires*, S. Hebeisen, and P. Soares-Da-Silva *BIAL - Portela & Ca. SA, So Mamede do Coronado, Portugal; BSYS GmbH, Witterswil, Switzerland; and University of Porto, Porto, Portugal
Purpose: Eslicarbazepine, the major (94.5%) active metabolite of eslicarbazepine acetate (ESL), preferentially enhances the slow inactivation of voltage-gated sodium channels (VGSC). This study was aimed to compare the effects of eslicarbazepine with the effects of R-licarbazepine and oxcarbazepine (OXC), two minor metabolites (5.0% and 0.5%, respectively) of ESL, on the fast and slow inactivated states of VGSCs. Method: The whole-cell patch-clamp technique was used to investigate the effects of eslicarbazepine, R-licarbazepine and OXC (all at 250 lM) on sodium channels endogenously expressed in N1E-115 cells, in conditions of fast and slow inactivation of sodium currents. Result: Steady state fast inactivation curves were shifted in the hyperpolarizing direction by OXC (-17 mV), but not by eslicarbazepine (-2.4 mV) or R-licarbazepine (-3.2 mV). OXC-treated fast inactivated channels required long pulses to recover (Dt = 391 ms), whereas eslicarbazepine- and R-licarbazepine-treated fast inactivated channels recovered similar to control conditions (Dt = 11 ms). The voltage dependence of the slow inactivation (shift V0.5) for OXC, R-licarbazepine, and eslicarbazepine was -28.1, )31.9, and )31.2mV, respectively. For eslicarbazepine, R-licarbazepine and OXC the affinity to the slow inactivated state was 5.9, 5.8, and 1.8 times higher than to the channels in the resting state, respectively. For eslicarbazepine, R-licarbazepine, and OXC, the time constants for entering the slow inactivated sate were 7.00, 7.03, and 12.36 s, respectively. Conclusion: Both eslicarbazepine and R-licarbazepine preferentially enhance the slow inactivation of VGSC, whereas OXC appears to modify kinetics and voltage-dependence of fast inactivation states.
p172 EXPOSURE-RESPONSE MODELING OF LACOSAMIDE IN ADJUNCTIVE TREATMENT OF PATIENTS WITH PARTIAL-ONSET SEIZURES C. Laveille*, R. Schoemaker*, and A. Stockis *Exprimo, Mechelen, Belgium; and UCB, Braine LAlleud, Belgium
Purpose: To develop a retrospective exposure-response model for lacosamide based on daily seizure counts of individual patients with focal epilepsy and to identify potential prognostic factors in reducing seizure frequency (SF) by performing a covariate analysis. Method: Individual daily seizure records (N=210,234) were obtained from 1308 patients who participated in three double-blind, placebo-controlled clinical trials (SP667, SP754, SP755). Probability of daily seizures was estimated by nonlinear mixed effects modeling using statistical distributions appropriate for count data. Plasma concentrations were estimated using a population pharmacokinetic model. Drug effect on seizure frequency reduction was modeled using a Hill function. Result: A negative binomial distribution with zero-inflation and Markovian element provided the best fit for all phases (baseline, titration, maintenance). Patients who were not taking concomitant sodium channel blocking (SCB) anti-epileptic drugs (AEDs; 18% of population) underwent a greater SF reduction from baseline compared with patients taking concomitant SCB AEDs (82%). The EC50 (trough concentration producing half the maximum SF reduction) was 4.6lg/mL (90%CI 3.55.7lg/ mL). Median SF reduction in improving patients was 23% (placebo), 48% (lacosamide with SCB) and 70% (lacosamide with non-SCB) at lacosamide 400mg/day. Conclusion: An exposure-response relationship was demonstrated between lacosamide plasma trough concentration and SF reduction from baseline in patients with uncontrolled focal seizures. The combination of lacosamide with non-SCB AED(s) resulted in greater reductions in SF compared with the combination of lacosamide with SCB AED(s), as identified previously (Sak et al, CNS Drugs 2010; 24:105568). UCB-sponsored.
p171 RUFINAMIDE AND LENNOX-GASTAUT SYNDROME: EFFICACY, TOLERABILITY AND NEUROPSYCOLOGICAL OUTCOME IN YOUNG PATIENTS C. Cerminara*, M. Pinci*, A. Luchetti, D. Battaglia, P. Curatolo*, M. G. Marciani, and A. Romigi *Tor Vergata University, Rome, Italy; Catholic University, Rome, Italy; and University of Rome Tor Vergata, Rome, Italy
Purpose: The aim of our study was to explore the effectiveness, safety and tolerability of rufinamide in young patients with LGS. Neuropsycological outcome has been valuated. Method: 24 patients of 631 years with LGS. These were treated with rufinamide added to the baseline therapy at the mean dose of 38.7 mg/kg/ die for a mean period of 44.5 weeks. Effectiveness was evaluated comparing the frequency of seizure between baseline period and. 3 months and 12 months after treatment beginning. Neuropsycological assessments were performed at baseline and at end point. Result: Rufinamide was effective on seizure in 58.3% of patients already after 3 months: 1 patient seizure free, 7 had 50% seizure
p173 QUALITY OF LIFE IN PATIENTS WITH MEDICALY REFRACTORY EPILEPSY TREATED WITH LEVETIRACETAM AS A MONOTHERAPY D. P. Cvetkovska, and E. Cvetkovska University Clinic for Neurology, Skopje, Macedonia
Purpose: To evaluate efficacy and tolerability of levetiracetam as a monotherapy in patients with medicaly refractory epilepsy Method: The study was randomized, prospective of 12-month duration and included 16 patients with newly diagnosed epilepsy. We evaluated
52 Abstracts
efficacy primary by evaluating reduction of seizure frequency and secondary by improvement of quality of life using QOLIE 89 questionnaire. We also registered development of adverse effects. Result: The patients were on age from 1465 years. From seizures types most representing was patients with SGS 46.5% and from etiological factors (by CT and MRI) most of the patients was with hyppocampal sclerosis, tumors and trauma. Analysis of reduction of seizures frequency show significant reduction >50% in 56.25% of patients, <50% in 18.75% of patients and without effects in 18.75% patients, without significant differences by seizures types (p<0.05). The improvement of QOLIE 89 score in levetiracetam treated patients was 72.5% also without significant differences by seizures types (p<0.05). Fatigue, somnolence, headache, and irritability were adverse effects considered drug-related and reported in 6% of patients. Conclusion: Our results suggest that levetiracetam is highly effective in treatment of patients with refractory epilepsy, probably due to reduction of seizure frequency, but also because of improvement of social, mood and cognitive function. Purpose: Eslicarbazepine acetate (ESL) is a novel once-daily voltagegated sodium-channel blocker approved in Europe for use in adults as adjunctive therapy for refractory partial-onset seizures (POS) with or without secondary generalisation. This phase III study aims to assess the efficacy and safety of ESL as adjunctive therapy in 252 children and adolescents (2 to 16-years old) with refractory POS, treated with 1 or 2 AEDs. Method: After an 8-week baseline-period, patients with >4 seizures/4weeks will be randomised (stratified by age: 26; 712 and 1316 years) in 1:1 ratio to ESL or placebo once-daily. Following titration to target dose of 20 mg/kg/day over a 6-week period, they will enter a 12-week maintenance-period. The primary endpoint is the responder rate (at least a 50% decrease in seizure frequency), based on patients seizure diaries. Secondary endpoints include changes in seizure frequency, the proportion of seizure-free patients and seizure duration and severity (Hague seizure severity scale). Safety will be assessed by adverse events, clinical laboratory tests, physical and neurological examinations, and measurement of growth and development. An open-label extension with the possibility of conversion to monotherapy in cases such as seizure freedom will follow the double-blind phase. Result: The study is expected to be completed by the end of 2012, and the results will be reported thereafter. Conclusion: ESL efficacy data in adults with POS cannot be extrapolated in this population. This study is designed to evaluate the risk/benefit ratio as part of the clinical development plan of ESL in children.
p174 EFFECTS OF LACOSAMIDE AND CARBAMAZEPINE ON HUMAN MOTOR CORTEX EXCITABILITY H. Peckolt, H. Rothkegel, G. Deuschl, and N. Lang UKSH Campus Kiel, Kiel, Germany
Purpose: Lacosamide (LCM) and carbamazepine (CBZ) are antiepileptic drugs both acting on neuronal voltage-gated sodium channels. Patchclamp studies have demonstrated that LCM enhances slow inactivation of voltage-gated sodium channels, and, in contrast to CBZ, does not affect steady-state fast inactivation. The enhancement of slow inactivation of sodium channels by LCM is a novel manner to modulate sodium channels and leads to normalization of activation thresholds and a reduced pathophysiological hyper-responsiveness, thereby effectively controlling neuronal hyperexcitability without affecting physiological activity. Method: The present study was designed to explore dose-depended effects of LCM on motor cortex excitability with transcranial magnetic stimulation (TMS) in a randomized, double-blind, placebo-controlled crossover trial in young healthy human subjects, and to compare the pattern of excitability changes induced by LCM with those of CBZ. Result: The two antiepileptic agents show distinct patterns, with differential neuronal inhibitory and excitatory subsystems involved. Conclusion: TMS can be used for testing acute drug effects at the systems level of the cerebral cortex in awake humans and offers a broad array of measures of motor cortical excitability, which cover different aspects of excitability, such as axon excitability, and distinct forms of inhibitory and excitatory synaptic excitability.
p176 DRUG RESISTANCE AND SEIZURE SEVERITY OF PATIENTS IN PARTIAL-ONSET SEIZURE REGISTRATION TRIALS OF PERAMPANEL COMPARED WITH RECENTLY APPROVED ANTIEPILEPTIC DRUGS G. L. Krauss*, F. Kerling, V. Villanueva, D. Squillacote, H. Yang, J. Zhu, L. Verdian, and A. Laurenza *Johns Hopkins University, Baltimore, MD, USA; Ulm University, Ulm, Germany; Hospital Universitario y Politcnico La Fe, Valencia, Spain; Eisai Neuroscience Product Creation Unit, Woodcliff Lake, NJ, USA; and Eisai Ltd, Hatfield, UK
Purpose: Successive registration studies of new adjunctive antiepileptic drug (AED) therapies recruit many patients resistant to newer AEDs. We describe baseline seizure frequency and demographic factors in perampanel registration trials in the context of 5 previously approved newergeneration AEDs. Method: We evaluated baseline seizure severity and baseline AED use in registration trials for perampanel, levetiracetam, zonisamide, lacosamide, eslicarbazepine and retigabine. Result: Mean patient ages (32.941.3 years) were similar across all 6 AED registration trials; mean duration of epilepsy was similar for perampanel (19.123.7 years) and the 5 other AEDs (15.725.4 years). Median number of seizures/28 days at baseline was generally higher for perampanel (9.314.3) versus other AEDs: levetiracetam (6.710.5); lacosamide (5.515.0); eslicarbazepine (6.79.0); and retigabine (7.912.1) (zonisamide data not available). More patients had a history of secondary generalized seizures in perampanel studies (67.971.9%) versus levetiracetam (26.027.0%); zonisamide (21.024.0%); lacosamide (43.8 78.8%); eslicarbazepine (28.247.1%); and retigabine (23.233.7%). A high proportion of these refractory patients required 3 concomitant AEDs at baseline in perampanel trials (28.938.6%) compared with most other AEDs: levetiracetam 5.05.1%; zonisamide 21.728.8%; lacosamide 0.036.9%; eslicarbazepine 0.09.9%; retigabine 0.033.8%. As the last of these registration studies, concomitant AEDs in perampanel studies

p175 A CLINICAL STUDY METHOD USED TO EVALUATE THE EFFICACY AND SAFETY OF NOVEL ANTIEPILEPTIC DRUG ESLICARBAZEPINE ACETATE IN EPILEPTIC CHILDREN WITH PARTIAL-ONSET SEIZURES F. Mota*, J. Moreira*, T. Nunes*, and P. Soares-Da-Silva *BIAL - Portela & Ca. SA, So Mamede do Coronado, Portugal; and University of Porto, Porto, Portugal
53 Abstracts
included all 2nd- and 3rd-generation AEDs available in 20082009; 71.5% of patients received at least one newer AED. Conclusion: Compared with registration trials for previous 2nd- and 3rd-generation AEDs, patients entering the perampanel trials generally had higher seizure frequencies, more often had histories of secondarily generalized seizures, and were receiving 3 concomitant AEDs. Support: Eisai Inc. Method: This was a Phase II, open-label extension of a pharmacokinetic and tolerability study, in which paediatric patients with uncontrolled seizures received adjunctive zonisamide (112 mg/kg/day; administered twice-daily). Patients were grouped by age at entry: 511 (n=20) and 12 18 (n=9) years. Safety assessments included adverse events (AEs), vital signs, physical examination and clinical laboratory tests, conducted monthly for the first 3 months, and then at 6 months. Some data were collected beyond 6 months since the original protocol specified treatment up to 12 months. Result: Overall, 24/29 (82.8%) patients completed the study. Mean exposure to zonisamide was 259 days. In total, 24/29 (82.8%) patients reported treatment-related AEs; most commonly, anorexia (37.9%), somnolence (34.5%) and asthenia (24.1%). Most AEs were mild/moderate in intensity. Ten new serious AEs were reported in five patients, only two of which were considered zonisamide-related. Few patients experienced clinically relevant laboratory abnormalities. Overall, 75.0% patients had bicarbonate levels below the normal range, and 28.6% had chloride levels above the normal range, at any time during the study. There were no reports of oligohydrosis, severe rash or renal calculi and no notable changes in body weight. Conclusion: Long-term zonisamide therapy was generally well tolerated in these paediatric epilepsy patients. Given the small sample size, further studies are needed to confirm these findings. Supported by Eisai.
p177 PHARMACOKINETICS AND TOLERABILITY OF ZONISAMIDE IN PAEDIATRIC PATIENTS WITH EPILEPSY: RESULTS OF A PHASE II, OPEN-LABEL STUDY L. Giorgi*, and I. Chouette *Eisai Limited, Hatfield, UK; and Eisai Europe Limited, Hatfield, UK
Purpose: Zonisamide is currently licensed for adjunctive treatment of adults with partial seizures (with or without secondary generalisation). This study aimed to characterise the pharmacokinetics and tolerability of zonisamide in paediatric epilepsy patients. Method: In this Phase II, open-label study, 33 paediatric patients (aged 515 years) with uncontrolled seizures received adjunctive zonisamide (112 mg/kg/day; administered twice-daily) for approximately 60 days. Steady-state pharmacokinetics, including observed maximum concentration (Cmax), area under curve to 12 h (AUC012h), apparent oral clearance (CL/F) and total body weight-normalised CL/F (CL/F/TBW), were assessed at zonisamide doses of 1, 7 and 12 mg/kg/day. Analysis was performed by age (511 and 1215 years) and concomitant use of CYP3A4inducing or non-inducing antiepileptic drugs (induced and noninduced patients). Tolerability was assessed by evaluating adverse events (AEs). Result: Overall, 21/33 (63.6%) patients completed the study. Zonisamide pharmacokinetics were dose-dependent and peaktrough fluctuations were relatively small over each 12-h evaluation period. Although patient numbers were too low for statistical comparison, the following observations were of note: for non-induced patients, Cmax, AUC012h and CL/F were numerically lower, and CL/F/TBW was numerically higher, in patients aged 511 versus 1215 years; in both age groups, Cmax and AUC012h were numerically lower, and CL/F and CL/F/TBW were numerically higher, in induced versus non-induced patients. Overall, 81.8% patients reported treatment-related AEs; most commonly, somnolence (30.3%), anorexia (27.3%), asthenia (21.2%), dizziness (15.2%) and nervousness (15.2%). Most AEs were mild/ moderate in intensity. Conclusion: Zonisamide displayed dose-dependent pharmacokinetics and was generally well tolerated in this paediatric epilepsy population. Supported by Eisai.
p179 EFFICACY AND TOLERABILITY OF LAMOTRIGIN MONOTHERAPY IN NEWLY DIAGNOSED EPILEPSY I. Marinkovic*, S. T. Ristic, H. Kocic, J. Cukuranovic*, and D. T. Ristic *Medical Faculty of Nis, Nis, Serbia; Clinical Centre of Nis, Nis, Serbia; Medical faculty University of Maribor, Maribor, Slovenia; and Institutae of Pulmonary Disaeses, Nis, Serbia
Purpose: Evaluation of Lamotrigine monotherapy outcome in epilepsy outpatients and comparison of adverse effects, in patients with newlydiagnosed epilepsy. Method: In open- label, non randomized, add-on trial over a period of 2 years, from January 2010. until January 2012. we analysed efficacy and tolerability of lamotrigin monotherapy in total of 147 untreated patients (84 male) with a recent diagnosis of epilepsy (41 idiopathic generalized epilepsy, 96 localisation- related epilepsy, 10 unclassified epilepsy). The follow-up period was minimum six months. Efficacy was classified as:1. remission without adverse effects; 2. remission with adverse effects; 3. >50% seizure reduction; 4. <50% seizure reduction; 5. seizure worsening. We analysed age at onset, manifestations and frequency of seizures, before and after treatment, tolerability and advese effects. Seizure frequency was compared before and after treatment. Result: A total of 147 patients (median age 48.15 years, range 1884) evaluable at this analysis. The median doses of lamotrigine was 250 mg./ daily. Remission without adverse effects was obtained in 62 patients (42.17%); remission with adverse effects in 29 patients (19.72%); seizure reduction of >50% in 39 patients (26.53%); seizure reduction of <50% in 14 patients (9.52%) and seizure worsening in 3 patients (2.04%). The tolerability of lamotrigine was generally good. The most frequent adverse effects were imbalance/dizziness (10.88%), headaches (6.80%), trembling (5.44%), epigastric discomfort (4.76 %), rash (2.72%). Therapy was withdrawn in 2 (1.36%) patients. Conclusion: Our study suggests high efficacy and good tolerability of lamotrigin in patients with newlydiagnosed epilepsy.
p178 LONG-TERM TOLERABILITY OF ZONISAMIDE IN PAEDIATRIC PATIENTS WITH EPILEPSY: RESULTS OF A PHASE II, OPEN-LABEL, EXTENSION STUDY I. Chouette*, and L. Giorgi *Eisai Europe Limited, Hatfield, UK; and Eisai Limited, Hatfield, UK
Purpose: Zonisamide is currently licensed for adjunctive treatment of adults with partial seizures (with or without secondary generalisation). This study aimed to characterise the long-term tolerability of zonisamide in paediatric epilepsy patients.
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p180 ANTIEPILEPTIC DRUG USE AND SEIZURE REFERRAL PATTERNS BY NON-EPILEPSY SPECIALISTS AT A LONDON REGIONAL NEUROSCIENCE CENTRE: A CLINICAL AUDIT D. P. Holland*, W. Hall, A. Blochberger, and H. Cock* *St. George's, University of London, London, UK; and St. George's Healthcare NHS Trust, London, UK
Purpose: Evidence based guidelines support the use of short term (714 days), prophylactic antiepileptic drugs (AEDs) for acute provoked seizures and/or patients at very high risk, but with no evidence of longer term benefit. Guidelines also recommend that all patients with suspected seizures or epilepsy have minimum safety information provided, and are promptly referred to an epilepsy specialist. We set out to audit clinical practice around stroke and neurosurgery patients with respect to AED initiation and seizures against published guidelines. Method: All in-patients initiated on AEDs under neurosurgery or stroke teams over a 4 month period were prospectively identified. Patients with a prior epilepsy diagnosis were excluded. Medical records were then retrospectively reviewed using a pre-designed audit proforma, including diagnoses, demographics, AED details (including duration), documented indication, follow up and referral. Result: 43 patients were identified of whom 1 died, and 2 were lost to follow up. Of the 40 patients included in the study, 30 AED initiations were undertaken by neurosurgery, meeting 59% of AED audit criteria. Stroke clinicians initiated AEDs in 10 patients, meeting 71% of AED audit criteria. Of the 20 who had seizures, 25% had documented counselling, and 25% were referred to epilepsy services. At least one audit criteria was not met in 73% of patients. Conclusion: Shortfalls exist in AED and seizure management in neurosurgical and stroke patients, with clinical governance and financial implications. Measures to promote the use of existing pathways and available expertise are now being implemented, and a re-audit planned. to the channels in the resting state, respectively. For eslicarbazepine and CBZ, the time constants for entering the slow inactivated state were 7.00 and 14.49 s, respectively. Conclusion: Eslicarbazepine does not share with CBZ the ability to alter fast inactivation of VGSC, but rather appears to modify the kinetics and voltage-dependence of slow inactivation states.
p182 CLINICAL EXPERIENCE WITH ORAL LACOSAMIDE AS ADJUNCTIVE THERAPY IN ADULT PATIENTS WITH UNCONTROLLED EPILEPSY: A MULTICENTRE STUDY IN EPILEPSY CLINICS IN THE UNITED KINGDOM R. D. Cary Elwes*, S. Kemp, L. Flores*, K. Colbeck, L. Nashef*, P. Goulding, and M. P. Richardson *King's College Hospital, London, UK; St Jame's Hospital, Leeds, UK; and King's College London, London, UK
Purpose: To evaluate the efficacy and tolerability of add-on Lacosamide in an out-patient epilepsy clinic setting to obtain useful information for everyday practice. Method: A retrospectively case note study of patients with refractory epilepsy was carried out in whom lacosamide had been prescribed in 19 hospitals across the United Kingdom. Result: Four hundred and three patients were included (mean age 41.9 years, 50.6% women, 18.1% with learning disabilities). Mean follow-up was 11.6 months (range one day to 42 months). Most (86.9%) had symptomatic partial epilepsy and were taking a mean of two other antiepileptic drugs. Retention rates were 80% at six months, 68% at one year and 45%t at two years. The efficacy of lacosamide was evaluated at three months and at the final FU. At three months one hundred and eight patients (31.1%) reported 50% seizure reduction and 32 (9.2%) were seizures free. At final FU 102 (37.5%) reported 50% seizure reduction and 28 (9.8%) were seizures free. One hundred and ninety three patients (48.7%) reported adverse effects (AEs). The most frequent were sedation and dizziness, followed by nausea. Lacosamide was discontinued in 150 patients (38%), mostly due to AEs and lack of efficacy. No major neuropsychiatric complications were identified and outcomes in cases with learning difficulties were similar to those without. Conclusion: Lacosamide appears to be an effective and safe AED when used as adjunctive therapy in patients with refractory partial epilepsy.
p181 SLOW AND FAST INACTIVATION OF VOLTAGEGATED SODIUM CHANNELS BY ESLICARBAZEPINE AND CARBAMAZEPINE P. Soares-Da-Silva*, and S. Hebeisen *BIAL - Portela & Ca. SA, So Mamede do Coronado, Portugal; and BSYS GmbH, Witterswil, Switzerland
Purpose: The efficacy of adjunctive eslicarbazepine acetate (ESL) in reducing the frequency of partial-onset seizures in adults receiving carbamazepine (CBZ) or another antiepileptic drug was similar (Epilepsia, 50, 454463, 2009; Epilepsy Res., 89, 278285, 2010). This study was aimed to determine the effects of eslicarbazepine, the major active metabolite of ESL, and CBZ on the fast and slow inactivated sates of voltage-gated sodium channels (VGSC). Method: The whole-cell patch-clamp technique was used to investigate the effects of eslicarbazepine and CBZ (both at 250 lM) on sodium channels endogenously expressed in N1E-115 cells, in conditions of fast and slow inactivation of sodium currents. Result: Steady state fast inactivation curves were shifted in the hyperpolarizing direction by CBZ ()12.0 mV), but not by eslicarbazepine ()2.4 mV). Eslicarbazepine-treated fast-inactivated channels recovered similarly to control conditions (Dt = 11 ms), whereas CBZ-treated channels required longer pulses to recover (Dt = 391 ms). CBZ shifted by )4.6 mV, the voltage dependence of the slow inactivation, whereas for eslicarbazepine the shift V0.5 was )31.2 mV. For eslicarbazepine and CBZ, the affinity to the slow inactivated state was 5.9 and 1.7 times higher than
p183 THE LONG-TERM EXPERIENCE OF MONOTHERAPY WITH OXCARBAZEPINE AND LEVETIRACETAM IN THE TERTIARY EPILEPSY CENTER J. Lim, B. S. Kang, J. Byun, B. S. Park, J. W. Shin, Y. S. Kim, K. Chu, and S. K. Lee Seoul National University Hospital, Seoul, Korea
Purpose: We tried to evaluate the long-term efficacy and safety of Oxcarbazepine (OCB) and Levetiracetam (LEV) treatment as monotherapy in the tertiary epilepsy center on broad population. Method: All patients who had been treated with LEV or OCB as monotherapy at Seoul National University Hospital from 2007 to March 2009 were recruited. The patients who had brain surgery for seizure control or who associated dynamic disease were excluded. Electronic medical records were retrospectively reviewed. Efficacy was measured using a five point scale. Adverse events were also recorded. Retention rates were calculated using life-table method.
55 Abstracts
Result: Total 184 patients with OCB were recruited, including 137 (89.1%) localization related epilepsy patients. Of total 188 patients with LEV, 127 (62.8%) patients were localization related epilepsy. Mean duration of follow up in group of OCB (67.4 month) was longer than in group of LEV (22.3 month). The seizure free rate in OCB and LEV was 53.3% and 61.7%. Tolerance in OCB was significantly higher than with LEV (21.7% versus 8.5%, P<0.001). Dose of LEV was inversely correlated with seizure free outcome and tolerance. The retention rates at 3-year were 78% in group of OCB and 75% in LEV. The incidence of adverse events of OCB was significantly higher than LEV (41.3% versus 24.5%, p<0.001). However, the incidence of irritability was higher in the patients with LEV (13.8%) than in OCB (3.8%). Conclusion: Oxcarbazepine and levetiracetam was effective and safe on monotherapy and the retention rates were well maintained up to three years. types of glutamate receptors. Recently, besides acting as an antiepileptic drug, it is also being investigated as a candidate in treating periodic limb movement disorder (PLMD). Here we report a case that has excellent response to topiramate in controlling PLMD, but later developed tardive dyskinesia involving jaw and tongue. Method: The detail medical history, clinical presentation, and responses to medications (including madopar, rivotirl, topiramate) of this patient were reviewed and summarized. The pathogenesis of PLMD, the mechanism of topiramate in controlling PLMD, a comparison with other medications, and a hypothesis in how topiramate might induce tardive dyskinesia are discussed. Result: Madopar and rivotril did not show any effect in controlling PLMD and later on the dyskinesia. Topiramate stopped the PLMD completely, however is suspected to have caused dyskinesia. Conclusion: While the mechanism of topiramate in controlling epilepsy, and the underlying pathogenesis of PLMD are not entirely understood, our case report might help in understanding both by providing evidence that ion channels and receptors may play a role.
p184 GENERIC SUBSTITUTION OF ANTIEPILEPTIC DRUGS A SURVEY OF THE PATIENT'S PERSPECTIVE K. Hensler*, C. Uhlmann, T. Porschen, R. Benecke*, and J. Rsche* *Universittsmedizin Rostock, Rostock, Germany; Sdwrttembergisches Zentrum fr Psychiatrie, Weissenau, Germany; and Landesverband fr Epilepsie Selbsthilfe Nordrhein-Westfalen e.V., Kln, Germany
Purpose: In this study we tried to determine the patient's attitudes to generic substitution of antiepileptic drugs (AEDs) and their experiences with the usage of generic antiepileptic drugs in Germany and other German speaking countries. Method: In April 2011 2000 copies of a 25-item questionnaire were delivered with a magazine edited by a patient's organisation. Each item consisted of a 5-point Likert scale. Additionally the questionnaire was placed on the internet platform of another patient's organisation from May to September 2011. We calculated Spearman correlation coefficients between the answers in different items. Result: When responses of relatives and of patients, who could not determine whether they had experiences with generic AEDs or not, were excluded, 99 paper questionnaires and 128 internet questionnaires could be analysed. 95% of the patients (128 female, 99 male) were from Germany. 112 (= 49%) patients reported experiences with generic substitution of AEDs. 34% of them complained about difficulties with the generic substitution (Likert scale 4 or 5) and 25.5% had a breakthrough seizure (Likert scale 4 or 5). 9.6% of the patients admitted compliance problems after generic substitution (Likert scale 4 or 5). Compliance problems were correlated with breakthrough seizures (r = 0.48, p < 0.001). Conclusion: A considerable amount of patients experiences breakthrough seizures after generic substitution of AEDs. The percentage of breakthrough seizures in our study is in line with results from earlier surveys in English speaking countries. Compliance problems may be the result or in some cases the cause of breakthrough seizures.
Neuroimaging and Neurophysiology 1 Monday, 01 October 2012

p186 ICTAL [99MTC] HMPAO SPECT IN NONLESIONAL EXTRATEMPORAL EPILEPSY E. Pataraia, S. Aull-Watschinger, R. Jung, T. Traub-Weidinger, and S. Asenbaum-Nan Medical University Vienna, Vienna, Austria
Purpose: Ictal SPECT has been applied successfully in temporal lobe epilepsy (TLE) to localize the seizure onset zone with high sensitivity, especially in mesial TLE. The sensitivity of ictal SPECT is significantly lower in extratemporal lobe epilepsies (ETLE). The delineation of the epileptogenic zone in patients with non-lesional ETLE is the major challenge in epileptology. The aim of the present study was to evaluate the clinical benefit of ictal SPECT in non-lesional extratemporal epilepsy (ETLE). Method: The patients with suspected non-lesional ETLE (non-localizing or discordant non-invasive data during the prolonged Video-EEGMonitoring and negative MRI) were subjected to ictal SPECT studies for planning invasive monitoring or surgery strategy. Ictal SPECT was considered to be useful for decision-making if it obviated the need for invasive monitoring or influenced its planning. Result: Ictal [99mTc] SPECT results of 25 patients (14 men, 11 women) with suspected non-lesional ETLE (mean age 32.689.6 years) were included in final analysis. The time from clinical onset of seizure and injection was from 6 to 38 sec (mean 13.289.07 sec). The patients were divided into two groups: those where the non-invasive evaluation presumed a seizure onset zone in one region (localizable), and those where the seizure onset zone was not lateralizable or localizable (non-localizable). Ictal SPECT was decided to be successful if it provided any additional information in regard to localization of epileptogenic zone. In 6 of 14 patients (43%) of localizable group ictal SPECT provided additional information, whereas only in 1 of 11 patients (9%) of non-localizable group ictal SPECT was helpful in decision-making and planning the invasive recordings (p=0.07). Additionally in 17 patients [18F] FDG and/ or [11C] FMZ PET were available. FDG and FMZ did not demonstrate any abnormalities except in one patient. Conclusion: Ictal SPECT provided more localizing information and influenced the final decision-making only in patients were based on the
p185 TOPIRAMTE AND DYSKINESIA Y. Liang*, H. Tsai, and C. Lo* *National Chen Kung University Hospital, Douliou branch, Yulin, Taiwan; and Chiayi Christian Hospital, Chiayi, Taiwan
Purpose: Topiramate is a sulfamate substituted monosaccharide. It acts to reduce voltage gated sodium channels and also enhances postsynaptic GABA-receptor currents and limits activation of the AMPA-kainate
56 Abstracts
non-invasive monitoring results the seizure onset zone could be localized to one region of the brain. In opposite to TLE clinical benefit of ictal SPECT preoperatively in non-lesional ETLE seems to be limited. Due to rapid changes of perfusion state peri-ictally (for example due to rapid seizure spread especially in frontal lobe epilepsy) successful ictal SPECT investigations might lack clinical benefit with respect to possible surgical interventions. These findings need to be validated in a larger group of patients. The subtraction with interictal SPECT would also improve these results. Method: A 15 year old boy with drug-resistant cryptogenic epilepsy underwent continuous EEG- fMRI acquisition using a 3T MR scanner. During the examination 26 interictal electric abnormalities were registered. The fMRI data analysis was performed by different event-related (ER) design adopting respectively canonical hemodynamic response function (HRF), Fourier and Finite Impulse Response (FIR) basis functions. The localization of activation/deactivation clusters obtained by each statistical approach was compared with the localization of the seizure onset zone obtained by invasive stereo-EEG. Result: Similar activation maps were obtained by ER design using FIR basis functions and Fourier basis functions as HRF. Both approaches provided clusters of activation concordant with the seizure-onset zone identified by depth electrodes. On the other hand, ER design combined with standard HRF was not able to identify clusters within the seizureonset zone. Conclusion: The ER approach using Fourier and FIR basis functions might provide adjunctive information with respect to standard HRF. The role of non-canonical approaches in identifying the epileptogenic zone needs to be evaluated on large series of patients.
p187 MAGNETOENCEPHALOGRAPHIC MEASURES OF ABNORMAL SENSORY OSCILLATIONS: A WINDOW ON PHOTOSENSITIVE EPILEPSY G. Perry*, L. M. Brindley*, S. M. Muthukumaraswamy*, K. Hamandi, and K. D. Singh* *Cardiff University, Cardiff, UK; and University Hospital of Wales, Cardiff, UK
Purpose: Photosensitivity is a common trait in a number of epilepsy syndromes. Measuring visual responses with magnetoencephalography (MEG) provides a unique opportunity for the non-invasive study of abnormal cortical oscillations in these patients. Evidence points to photosensitivity being due to abnormalities in cortical inhibition, and this may be reflected in oscillations in the gamma frequency range (30100Hz), which are believed to reflect GABAergic inhibitory processes. The purpose of the present study was to use MEG to identify differences in these oscillations between photosensitive patients and non-photosensitive controls. Method: Data were collected from ten patients with photosensitive epilepsy and two age-matched control groups. Participants underwent MEG recording while viewing static visual gratings. Responses were localised to the visual cortex and the relationship between visually-induced oscillations and stimulus parameters (contrast and size) were compared between the different participant groups. Result: Contrary to our expectations, we did not find clear evidence for a difference between groups in the main gamma-band response (40 70Hz). Instead our results suggest differences at a lower frequency around 28Hz, and in the alpha frequency (812Hz) range. Conclusion: Our evidence suggests that there may indeed be characteristic differences in visually-induced oscillations between individuals with photosensitive epilepsy and controls, which may have potential use as diagnostic markers. The finding of differences in the high beta/low gamma and alpha frequency ranges suggests that pathophysiological disturbances may be localised to thalamo-cortical processes, and thus our data could guide future research into the mechanisms of seizure generation in photosensitive epilepsy.
p189 STRESS AFFECTS EMOTIONAL PROCESSING IN LEFT TEMPORAL LOBE EPILEPSY J. Szaflarski, J. Allendorfer, H. Heyse, and L. Mendoza University of Cincinnati Academic Health Center, Cincinnati, OH, USA
Purpose: To assess how stress (S) affects emotion processing in patients with left temporal lobe epilepsy (LTLE). Method: Included were 22 LTLE patients who believed (+S; n=15) and did not believe (-S; n=7) that stress played a role in their seizure control. Subjects were presented a pseudo-randomized series of faces with different expressions (happy/fearful/sad/neutral) during fMRI and instructed to press 1 for male and 2 for female face. After scanning, subjects were asked to indicate the expression on each of the previously presented faces; fMRI analysis only included correctly rated faces. FMRI image coregistration, spatial normalization, single-subject and group statistical modeling, and visualization were performed using AFNI. Single-subject fMRI response to emotion was determined using general linear modeling (happy, fearful, or sad faces contrasted with neutral faces). Group differences in neural processing of each emotion were performed using 2-sample t-tests (p<0.05, cluster threshold of 20 voxels). Result: Overall accuracy on post-scan rating of faces was better for -S than +S (p=0.012); the +S showed overall greater involvement of the prefrontal and medial temporal/amygdala regions. The groups also showed differential patterns of activation for each emotion (fear/sadness/happiness). Compared with -S, +S exhibited diminished response particularly in superior frontal regions when processing fear and sadness, but increased response in left temporal regions when processing happiness. Conclusion: Patients who do and do not believe that stress affects their seizure control recruit different brain regions during emotional processing; this difference may underlie the decreased accuracy of +S patients in rating emotional faces. (Support: Shor Foundation for Epilepsy Research).
p188 COMPARISON OF EEG-FMRI DATA TO INVASIVE ELECTROPHYSIOLOGICAL REGISTRATION IN CRYPTOGENIC FOCAL EPILEPSY I. Pesaresi*, S. Fabbri, C. Barba, E. Bartolini, P. Cecchi, F. Giordano, F. M. Quaglia, D. Pruna, M. Cosottini, and R. Guerrini *AOUP, Pisa, Italy; Pisa University, Pisa, Italy; Children's Hospital Meyer, Florence, Italy; Pisa University, Pisa, Italy; and Azienda Ospedaliero Universitaria of Cagliari, Cagliari, Italy
Purpose: To compare different methodological approaches in a patient with cryptogenic epilepsy who underwent invasive neurophysiologic investigation.
p190 IDENTIFICATION OF THE EPILEPTOGENIC ZONE BY EEG-FMRI: CONCORDANCE BETWEEN PRE-SURGICAL EEG-FMRI AND SUBSEQUENT STEREO-EEG DATA L. Mirandola*, M. Pugnaghi*, F. Benuzzi*, P. Avanzini, G. Cantalupo, G. Lo Russo, L. Tassi, and S. Meletti*
57 Abstracts
*University of Modena and Reggio Emilia, Modena, Italy; University of Parma, Parma, Italy; and Ospedale NiguardaCa Grande, Milano, Italy
Purpose: To illustrate a paradigmatic case of concordance between presurgical EEG-fMRI and subsequent Stereo-EEG data. Method: We report the case of a 27 year-old left-handed man, who underwent epilepsy surgery after an extensive pre-operatory investigation. Epilepsy started at age of 5 months. Staring, flushing, and bimanual automatisms characterized his drug-resistant partial seizures. The patient underwent prolonged Video-EEG recordings and two EEGfMRI studies, both performed with subsequent Independent Component Analysis (ICA) on EEG data. He also performed an intracranial monitoring. Result: Scalp EEG revealed bilateral frontal interictal paroxysmal abnormalities, while prolonged video-EEG recordings showed a left fronto-temporal localization of ictal events. Different interictal spikes dataset (ISD) were recorded during the first EEG-fMRI study and two distinct cluster of BOLD signal increase were identified: one located in the left frontal pole and the other in the ipsilateral dorso-lateral frontal cortex. Structural brain MRI revealed thickening and blurring of the fronto-polar cortex suggesting the presence of a focal cortical dysplasia and a tailored cortectomy involving the fronto-polar region was then performed. After three-months seizure-free period the patient experienced seizures recurrence. Post-operative EEG-fMRI, with the recording of ISD and one ictal event, and intracranial EEG results with the recording of several seizures, confirmed the involvement of the dorso-lateral frontal cortex, spared by the first cortectomy. In conclusion this data show how EEG-fMRI could identify the epileptogenic zone as demonstrated by concordance with Stereo-EEG results and clinical outcome. It represents a promising tool that should be implemented in the diagnostic work-up of patients with surgically-remediable epilepsies.
p192 HOW TO IMPROVE THE YIELD OF FDG-PET IN THE PREOPERATIVE WORK-UP FOR EPILEPSY SURGERY M. A. Van T Klooster*, F. S. S. Leijten*, G. J. M. Huiskamp*, R. M. C. Debets, E. F. I. Comans, S. Bouvard, and P. Ryvlin *UMC Utrecht, Utrecht, The Netherlands; 2 Epilepsy Institute of The Netherlands Foundation (SEIN), Heemstede, The Netherlands; VU University Medical Center, Amsterdam, The Netherlands; CERMEPImagerie du Vivant, Lyon, France; and Institute for Child and Adolescent with Epilepsy (IDEE), Hospices Civils de Lyon, Lyon, France
Purpose: Fluorodeoxyglucose PET (FDG-PET) is a costly, semi-invasive, interictal method to localize epileptogenic foci, marked by decreased FDG uptake. Since PET facilities and experienced reviewers are scarce we investigated how to improve the yield of the preoperative FDG-PET scan. We, retrospectively, compared three FDG-PET assessments to ictal electrocorticography (ECoG): initial clinical visual assessment (PETclin), blinded visual re-assessment (PETre) and Statistical Parametric Mapping (SPM) analysis (PETspm). Method: 44 Refractory focal epilepsy patients (mean age 25y, 19 female, 75% extra-TLE) who underwent chronic ECoG monitoring were included. All patients and 38 healthy controls underwent a static FDGPET scan (ECAT EXACT HR+). PETclin reports were collected. PETre was executed by the same two experts as for PETclin. Thirdly, PETspm was performed; each patient scan was compared, at cluster level (puncorr<0.001), to the healthy controls. The ictal ECoG electrodes were co-localized. Results were classified into ten predefined brain anatomical regions, and analysed on group (kappa, sensitivity, specificity) and patient level. Result: The number of scans without abnormalities for PETclin, PETre and PETspm were 5, 1 and 0, respectively, without overlap. Preliminary results indicate that PETre increases the overall sensitivity compared to PETclin, maintaining equal specificity. On patient level PETspm reveals new results in case of normal PETclin, or additional information regarding the focus. Conclusion: Visual re-assessment should be considered when initial assessment is negative. We advise to use more than one method when judging a FDG-PET scan in these types of difficult patients since re-evaluation has the potential to increase epilepsy surgery eligibility.
p191 UNVEILING THE MYSTERY OF DJ VU M. Brazdil*, R. Marecek, T. Urbanek, T. Kasparek, M. Mikl, I. Rektor*, and A. Zeman *Brno Epilepsy Center, Brno, Czech Republic; CEITEC MU, Brno, Czech Republic; Academy of Sciences of the Czech Republic, Brno, Czech Republic; Masaryk University, Brno, Czech Republic; and University of Exeter, Exeter, UK
Purpose: Dj vu is an eerie experience that is characterized by the recognition of a situation concurrent with the awareness that this recognition is inappropriate. This feeling of irrelevant familiarity is a common phenomenon occurring both in clinical (mainly epileptic) and nonclinical population. Despite numerous theories have been suggested as to what nonpathological dj vu is and what causes it, until now no ultimate explanation has been generally accepted. Method: We investigated differences in brain morphology between healthy subjects with and without dj vu using a novel multivariate neuroimaging technique, Source-Based Morphometry. Result: The analysis revealed a set of cortical (predominantly mesiotemporal) and subcortical regions in which there was significantly less gray matter in subjects reporting dj vu. In these regions gray matter volume was inversely correlated with the frequency of dj vu. Conclusion: Our results demonstrate for the first time a structural correlate of dj vu in healthy individuals and implicate a direct pathogenetic link between nonpathological and epileptic dj vu. We hypothesize our findings reflect an alteration of hippocampal function and postnatal neurogenesis in subjects with dj vu.
p193 MULTIMODAL EVOKED POTENTIALS BE USEFUL TOOL IN THE STUDY OF ENCHEPHALOPATY WITH STATUS EPILEPTICUS DURING SLOW SLEEP REPORT 5 CASES P. A. Ruiz, J. J. Ortega, J. R. Diaz, A. D. Ghinea, E. Canovas, and J. M. Pinzon Hospital General De Castellon, Castellon De La Plana, Spain
Purpose: Encephalopathy with status epilepticus during sleep is characterized by severe impairment of neuropsychological development, characteristic EEG pattern of continuous spike-wave during slow sleep and seizures in children. We appreciate the usefulness of Multimodal Evoked Potentials in the diagnosis and evolution of this disorder. Method: We studied 5 children (mean 7 years old) with ESES with severe developmental deficit and few seizures; we performed a Polysomnogram, Neuropsychological Development Test and Visual-Evoked Potentials, Somatosensory-Evoked Potential and Cortical and Brainstem Auditory-Evoked Potential. Only in cases found altered evoked potentials, we make annual checks, followed until the continuous spike-wave
58 Abstracts
pattern during sleep was resolved. Normal values were taken from a group of healthy children (313 years). Result: Four cases showed a rate spike-wave in slow sleep > 85% and seizures. Three cases, showed behavior disorders and severe deterioration in the language area. Find a delay P100 wave in VEP of two cases with significant visual deficit. PEAC was altered in a case with Auditory Verbal Agnosia, showing normal BAEP; and SSEP was normal in all cases. These alterations disappear at the same time it solves the continuous spike-wave pattern of sleep EEG. Conclusion: EPs have been studied as diagnostic evidence for epilepsy, but there are few data on the usefulness of Multimodal Evoked Potentials in children with ESES. The close relation between changes in EP and the EEG is very important redefine which neuro-behavioral areas would be involved in patients with this encephalopathy, being useful in the diagnosis and evolution. correlates with underlying pathological changes of tubers, as well as their epileptic potential. Method: In this study we plan to analyze the perfusion patterns both within tubers and in the surrounding perilesional regions in two populations of TSC patients, those with epilepsy (6 patients), and those with no history of seizures (6 patients). Epileptic tubers will be cross-identified with scalp EEG, and this data will be correlated with ASL perfusion maps. Result: We have obtained and analyzed ASL and MRI data on 4 TSC patients with epilepsy. Thus far, it appears that epileptic tubers and surrounding perilesional areas show hyperperfusion in comparison with average cerebral blood flow. Analysis of the nonepileptic tubers reveals no significant differences in perfusion compared to average cerebral blood flow. Conclusion: Our preliminary data shows that ASL can accurately identify epileptic networks in TSC. Using ASL to identify epileptic networks can be potentially applied to all patients with neocortical epilepsy, with the ultimate goal of improving seizure freedom rates from resective surgery.
p194 MESIAL TEMPORAL SCLEROSIS WITH MRI SIGNALS EXTENDING TO THE FORNIX S. Baz*, A. Alsemari, and F. Almuhailib *KFSHRC, Riyadh PO Box 3354, Saudi Arabia; and King Faisal Specialist Hospital & Research Centr, PO Box 3354, Saudi Arabia
Purpose: Mesial temporal sclerosis had been reported with ipsilateral fornix atrophy, however the extension of the MRI signals to the fornix is seldom reported. Method: To demonstrate the clinical, electrophyological and the imaging data of the findings. Result: 39 years old lady with refractory left temporal lobe epilepsy since adolescent on multiple anti-epileptics admitted to epilepsy monitoring unit for surgical evaluation. 5 seizures were captured at different interval then MRI was arranged several days after the last seizures. It showed mesial temporal sclerosis but with minor swelling of mesial temporal structures and a significant signal intensity and swelling of the fornix. The patients had slightly bigger sized fornix and mesial temporal structures several days after repeated seizures. However the previous MRI brain few years earlier demonstrated thin asymmetric left fornix. Conclusion: Recurrent seizures may influence the apparent thickness of the fornix however other possibilities may be entertained as neoplastic infiltration or inflammatory process.

p196 THE EFFECT OF GENERALIZED SPIKE AND WAVES DISCHARGE DURATION AND IGE SUB-SYNDROME ON BRAIN NETWORKS AS REVEALED BY EEG-FMRI M. Pugnaghi*, D. W. Carmichael, A. Vaudano, U. J. Chaudhary, F. Benuzzi*, C. Di Bonaventura, A. T. Giallonardo, R. Rodionov, M. C. Walker, J. Duncan, S. Meletti*, and L. Lemieux *University of Modena and Reggio Emilia, Modena, Italy; UCL Institute of Child Health, London, UK; University of Rome La Sapienza, Rome, Italy; UCL Institute of Neurology, London, UK; and Department of Clinical and Experimental Epilepsy, London, UK
Purpose: To investigate the hemodynamic correlate of generalized spike wave discharges (GSWD) duration and in particular the relationship between discharge duration and the magnitude and extent of the BOLD changes. Method: We studied 42 adult patients with Idiopathic Generalized Epilepsies (IGE) who underwent simultaneous recordings of EEG and functional MRI (EEG-fMRI) in three centres (London, UK; Modena and Rome, Italy). We applied a parametric analysis at the single subject level in order to explore the presence of non-linear effects of duration of GSWD on the BOLD changes. A full-factorial ANOVA design was performed as a random effect group analysis to model possible effects of IGE sub-syndrome and different MRI scanners. Result: The group analysis of the GSWD linear effect revealed BOLD signal changes in a network of brain regions: mainly transient BOLD increases in the thalami and bilateral insulae, and transient BOLD decreases in the posterior cingulate, precuneus and bilateral parietal regions. No significant non-linear effect of GSWD duration on BOLD was found. The full-factorial ANOVA analysis disclosed no main effect of the MRI scanner across the three centres, and no main effect of the sub-syndrome. Conclusion: Our findings support the idea that the amplitude of the BOLD response is linearly related to the GSWD duration with no
p195 LOCALIZING EPILEPTIC NETWORKS IN TUBEROUS SCLEROSIS USING ARTERIAL SPIN LABELING MRI PERFUSION A. Azarion, and K. A. Davis Hospital of the Univeristy of Pennsylvania/University of Pennsylvania School of Medicine, 4127829, USA
Purpose: The goal of this study is to utilize the noninvasive technique of arterial spin labeling (ASL) magnetic resonance imaging (MRI) to identify epileptic networks in patients with tuberous sclerosis complex (TSC), a subtype of neocortical epilepsy. Given that patients with TSC often have better seizure control after surgical resection of epileptic lesions as well as the neighboring perilesional tissue, this cohort is ideal for testing the hypothesis that ASL can accurately identify epileptic networks. Recent studies have shown that the quantitative ASL signal
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non-linear (or threshold) effect of duration. These results do not support the existence of a critical GSWD duration underlying consciousness impairment.
p197 SPECT PERFUSION PATTERNS IN PAEDIATRIC EPILEPSY OF TEMPORAL LOBE ORIGIN CORRELATION WITH SURGICAL OUTCOME P. S. Lakkunta*, S. J. Sattaluri, and M. Panigrahi *Krishna Institute Of Medical Sciences, Secunderabad, India; and Cecunderabad, India
Purpose: To assess the role of ictal SPECT in paediatric Temporal lobe epilepsy (TLE) and to correlate Ictal perfusion patterns with Surgical outcome. Method: A retrospective analysis of Ictal & Interictal SPECT, Ictal Video EEG, MRI and surgical outcome was performed in 27children of TLE. SPECT Perfusion patterns were classified as Typical (anteromedial, anterolateral, inferior) and Atypical (extra temporal). Surgical outcome was assessed according to Engel's classification. Result: Ictal and Interictal SPECT were done in 21, Interictal alone in 6. Sixteen had Hippocampal sclerosis (HS), while nonHS group had neuronal loss in four, Dual pathology in two, FCD in 2, ganglioglioma in 1, gliosis in one and normal in one . Sensitivity of ictal SPECT is 95%, interictal is 78%. SPECT was diagnostic in 85.7% of normal MRI patients. Typical pattern with anteromedial and lateral hyperperfusion is commonest in HS (75%). Atypical pattern is more commonly seen in nonHS group than with HS (45.4% vs 25%). 91.6% of HS group with typical pattern are in Engel's class 1 outcome. Whereas 80% of nonHS group with atypical pattern are in poor surgical outcome (p < 0.05). Conclusion: Ictal SPECT is highly sensitive (95%) in pre surgical evaluation of paediatric TLE. Typical pattern is commonest in HS (75%) and shows good surgical outcome. Significant association of atypical pattern with poor surgical outcome is noted in nonHS group (p value<0.05).
p199 CONVERGENT EVIDENCE OF REGIONAL THALAMIC ABNORMALITIES IN MESIAL TEMPORAL LOBE EPILEPSY S. S. Keller, C. Traynor, J. OMuircheartaigh, G. J. Barker, W. Crum, and M. P. Richardson King's College London, London, UK
Purpose: Multiple MRI studies have revealed global thalamic atrophy in human mesial temporal lobe epilepsy (mTLE). In animal limbic epilepsy, the medial nuclei of the thalami have been described as the consistent neuroanatomical alteration (Bertram et al., 2001, Epilepsia; 42:967). Using MRI and DTI, we sought to investigate the topology of intra-thalamic alterations in mTLE. Method: For 12 patients with mTLE and 18 healthy controls, we acquired DESPOT structural sequences for T1 and T2 mapping of six thalamic sub-regions per hemisphere based on a previously described protocol (Traynor et al., 2011, Neuroimage; 56:939) and DTI sequences for connectivity-based segmentation of the thalamus (Behrens et al., 2003, Nat Neurosci; 6:750) using a 3 T GE system. T1/T2 thalamic maps used the work of Morel et al. (1997, J Comp Neurol; 387:588) for anatomical reference. Result: Left (p=0.03) and right (p=0.02) Region 5 (including anteroventral, anteromedial, and ventral lateral posterior nuclei), and right (p=0.01) Region 3 (including medial pulvinar, mediodorsal and central lateral nuclei) were significantly reduced in volume in patients relative to controls. Furthermore, right Region 3 had significantly greater T2 values in patients (p=0.01). From connectivity-based segmentation, the thalamic sub-region classified as connecting to the right temporal target region was significantly smaller in patients (p=0.05). Conclusion: Thalamic sub-regions known to connect with the hippocampus are architecturally altered in mTLE. These thalamic regions may represent a central hub for the propagation and synchronisation of temporal lobe seizures, mediating the spread of hippocampal epileptiform activity to neocortex.
p198 FUNCTIONAL CONNECTIVITY STUDY IN PATIENTS WITH TEMPORAL LOBE EPILEPSY AND DEPRESSIVE SYMPTOMS R. Rocamora*, N. Roe-Vellve, R. M. Vivanco-Hidalgo*, M. Picado, B. Villoria*, A. Merino*, C. Garcia-Ribera*, A. Bulbena*, and O. Vilarroya *Parc de Salut Mar-Hospital de Mar, Barcelona, Spain; and Fundacio IMIM, Barcelona, Spain
Purpose: Our objective is the evaluation and characterization of neurofunctional, psychopathologic and neuropsychologic abnormalities present in a group of 15 TLE patients and 15 healthy controls. Method: We obtained fMRI scans from all participants and performed resting state analyses based on ROIs in order to study markers associated with abnormalities in functional connectivity relate to mood alterations. Result: Our preliminary results indicate hyperactivation in right anterior cingulate cortex (ACC), bilateral thalamus and insula; and hypoactivation in the left amygdala in the TLE patients as compared with the control group. We also performed a-priori ROIs of thalamic and ACC regions, which previous studies relate with depression. We found increased activation in such areas correlated with depression symptoms severity. Conclusion: Our results indicate the presence of neurofunctional differences in TLE patients that might be due to shared neural pathophysiological abnormalities underlying both epilepsy and depression, and might explain the presence of mood alterations in epilepsy.
p200 MR IMAGING IN STATUS EPILEPTICUS SECONDARY TO PARANEOPLASTIC ENCEPHALITIS S. Sarria, M. Toledo, C. Lorenzo I Bosquet, E. Lainez, S. Siurana, C. Auger, E. Santamarina, X. Salas-Puig, R. Mitjana, C. Vert, L. Fraschieri, and A. Rovira Vall dHebron University Hospital, Barcelona, Spain
Purpose: Patients with systemic cancer may have new-onset status epilepticus (SE) as the main clinical feature of paraneoplastic encephalitis. Five such patients who underwent MRI during SE or immediately after recovery are described. Method: We retrospectively reviewed the MR scans of five consecutive patients who experienced SE as the onset of paraneoplastic encephalitis between January)2005 and July-2011. All patients met the criteria for paraneoplastic syndrome. Three patients had small-cell lung carcinoma, two of them with anti-Hu antibodies. The two remaining patients had intestinal and lung adenocarcinoma. The SE episode was convulsive in two patients and none-convulsive in three patients. Result: All patients showed hyperintense lesions on T2-weighted images involving the limbic structures, specifically the hippocampus. Three patients additionally had scattered extralimbic areas of high-signal intensity. The T2 hyperintensities were related to the electroclinical onset of the seizures. Perfusion MRI obtained with arterial spin labeling (ASL) in one patient showed hyperperfusion overlapping the inflammatory lesions. SPECT and PET performed in 4 patients demonstrated increased metabolism limited to the areas of encephalitis. Mild to moderate contrast
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enhancement was seen in only one patient. In images performed following recovery, atrophy of the affected hippocampus was observed. In two patients who had recurrent paraneoplastic encephalitis manifesting as SE, new T2 lesions with a different topography were detected. Conclusion: Limbic and extralimbic encephalitis can be secondary to paraneoplastic syndrome in new-onset SE. MR study shows consistently hyperintense lesions on T2-weighted imaging, sometimes with mild contrast enhancement, and increased perfusion or metabolism as demonstrated by ASL or PET/SPECT. Method: The EEG-functional MRI (fMRI) was used to measure the resting state functional connectivity during interictal GSWDs in drugnave CAE, and three different brain networksthe default mode network (DMN), cognitive control network (CCN), and affective network (AN)were investigated. Result: Cross-correlation functional connectivity analysis with priori seed revealed decreased functional connectivity within each of these three networks in the CAE patients during interictal GSWDS. It included precuneus-dorsolateral prefrontal cortex (DLPFC), dorsomedial prefrontal cortex (DMPFC), and inferior parietal lobule in the DMN; DLPFC-inferior frontal junction (IFJ), and pre-supplementary motor area (pre-SMA) subregions connectivity disruption in CCN; ACC-ventrolateral prefrontal cortex (VLPFC) and DMPFC in AN; There were also some regions, primarily the parahippcampus, paracentral in AN, and the left frontal mid orb in the CCN, which showed increased connectivity. Conclusion: The current findings demonstrate significant alterations of resting-state networks in drug nave CAE subjects during interictal GSWDs and interictal GSWDs can cause dysfunction in specific networks important for psychosocial function. Impairment of these networks may cause deficits both during and between seizures. Our study may contribute to the understanding of neuro-pathophysiological mechanism of psychosocial function impairments in patients with CAE.
p201 DYNAMIC EFFECTIVE CONNECTIVITY OF EPILEPTIC NETWORKS DETERMINED WITH HIGH DENSITY EEG SOURCE ANALYSIS S. Vulliemoz*, R. Tyrand, L. Astolfi, B. He, M. Seeck*, C. Michel*, and G. Plomp *University Hospital of Geneva, Geneva, Switzerland; University of Geneva, Geneva, Switzerland; La Sapienza University, Roma, Italy; and University of Minnesota, Minneapolis, USA
Purpose: Analyzing the dynamic behaviour of epileptic networks could help to better understand the way pathologic neural activity propagates, and leads to spikes, seizures, and their electro-clinical and cognitive manifestations, with implications for epilepsy surgery candidates. Method: In 6 patients with temporal lobe epilepsy we studied effective connectivity of large-scale cortical networks at high temporal resolution around interictal spikes, recorded with high density (256 channels) EEG. The cortical electric source activity was obtained for 90 cortical regions of interest (ROI) using a distributed inverse solution. Multivariate, timevarying (millisecond resolution), and frequency-resolved (150Hz) Granger causality analysis (Partial Directed Coherence) was applied to the source signal for all ROIs. In all patients subsequent intracranial recording or surgical resection was used for validation. Result: Information flow occurred predominantly in the theta and beta bands. The key driving structures where located in the anterior and medial temporal regions, with peak information transfer before the spike maximum. We found fast-varying connectivity patterns between the antero-medial and lateral temporal lobe and basal frontal lobe, but also transient transfer towards the contralateral temporal lobe. In two patients with a multifocal irritative zone, we found evidence of connectivity from the main anterior temporal driver towards the secondary spike focus remote from the epileptogenic zone. Conclusion: EEG-based time-varying effective connectivity of epileptic spikes provides a clear characterization of the epileptic networks that is concordant with invasive electro-clinical findings. This could have major clinical implications for tailoring resective, disconnective, and functional surgery.
p203 COMPARISON OF FDG-PET AND ICTAL SPECT IN CHILDREN WITH FOCAL EPILEPSY UNDERGOING PRE-SURGICAL EVALUATION N. Vora*, V. I. Venegas, L. Biassoni, H. Cross, and C. M. Eltze *Lilavati Child Neuro Care, Ahmedabad, India; Clinica Alemana Santiago, Las Condes Santiago de Chile, Chile; Great Ormond Street Hospital for Children, London, UK; UCLInstitute of Child Health, London, UK; and University College London, Institute of Child Health, London, UK
Purpose: Ictal SPECT and fluorodeoxyglucose (FDG) - PET provide additional information to localise the epileptogenic zone especially when magnetic resonance imaging (MRI) is negative. Requirements for videoEEG and tracer injection close to seizure-onset pose logistic difficulties that may limit usefulness of ictal SPECT in pre-surgical evaluation. Here we compare the yield of ictal SPECT and FDG-PET in children with focal epilepsy undergoing pre-surgical evaluation. Method: Children evaluated in the supra-regional epilepsy surgery program who underwent both ictal SPECT and FDG-PET were identified. Reports issued by the program radiologist were analyzed. Additional clinical information was obtained from patient's records. Result: 24 children (14 males, mean age of seizure onset 3.5 years, sd +/)3.4) were identified, of which MRI was negative in 18 (75%). Ictal EEG was focal in 13 (54%) cases, concordant with FDG-PET in 5 and SPECT in 6. FDG-PET provided localising information in 17 (71%) and SPECT in 14 (58%) cases with concordance of both in 10 (42%). In 7 children with focal FDG-PET changes, ictal SPECT was not localising (5 multifocal/bilateral, 2 negative), whilst SPECT indicated a focal lesion in 4 with non-localising FDG-PET (2 multifocal/bilateral, 2 negative). Surgery was offered to 11 children (45%). Conclusion: FDG-PET provided additional localising information in a large proportion of mostly MRI negative patients justifying selective utilisation of Ictal SPECT. The high proportion of discordance of both imaging modalities emphasises the importance of a multidisciplinary approach considering multiple data sources i.e. neurophysiology, neuropsychology and other structural/functional imaging modalities.
p202 ALTERED RESTING-STATE CONNECTIVITY DURING INTERICTAL GENERALIZED SPIKE-WAVE DISCHARGES IN DRUG-NAVE CHILDHOOD ABSENCE EPILEPSY T. Yang, C. Luo, Q. Gong, and D. Zhou West China Hospital, Sichuan University, Chengdu, China
Purpose: To investigate the intrinsic brain connections at the time of interictal generalized spike-wave discharges (GSWDs) to understand their mechanism of effect on brain function in untreated childhood absence epilepsy (CAE).
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p204 EX VIVO HIGH-RESOLUTION MR (7T) MICROSCOPY OF THE HUMAN HIPPOCAMPUS R. Coras*, R. Garbelli, G. Milesi, C. Frassoni, I. Zucca, A. Mastropietro, A. Mhlebner*, A. Hess, E. Aronica, I. Blmcke*, and R. Spreafico *University Hospital Erlangen, Erlangen, Germany; I.R.C.C.S. Foundation Neurological Institute, Milan, Italy; University of Erlangen-Nuremberg, Erlangen, Germany; and Academic Medical Centre, Amsterdam, The Netherlands
Purpose: The human hippocampus is morphologically affected in many neurological disorders such as Alzheimer's disease or mesial temporal lobe epilepsy (MTLE). Its internal structure remains, however, difficult to recognize at 1.5T- or 3T-MR imaging. Herein, we aimed to anatomically delineate all subregions and layers of the human hippocampus combining high-field 7T-MRI and microscopy from same tissues specimens. Method: Different imaging protocols were applied on a 7T experimental scanner to examine eight post-mortem human hippocampus specimens. Anatomical layers along the anterior-posterior axis of the hippocampus were characterized on T2-weighted coronal sections. Histological analysis of same specimens was performed to co-register and validate 7T-MRI. Three-dimensional T2-weighted imaging and coronal planes with different angulations were acquired to anticipate the arched shape of the hippocampal head. Fractional anisotropy and color fiber orientation maps were used to visualize intrahippocampal projections and fiber tracts. Result: MR-Intensity differences between anatomical boundaries were confirmed by exact confrontation with histology and could be assigned to ten clearly recognizable layers. These findings were best visible at the hippocampal mid-body-level. We were able to distinguish all these hippocampal subregions also in the hippocampal head with three-dimensional T2-weighted imaging and angulated coronal planes. Fractional anisotropy and color fiber orientation maps visualized intrahippocampal projections and fiber tracts connecting the hippocampus with the mesial temporal lobe. Conclusion: High resolution MR-microscopy identified anatomical subcompartments and sublayers as well as distinct fiber tracts along the entire anterior-posterior hippocampal axis, and will be a promising tool for the investigation of subtle pathology in neurological or neurodegenerative disorders. using F-contrasts across the alpha and beta band effects (taken separately and together). Result: a bands were from sensory cortex, b bands were predominantly recorded from primary motor cortex. During finger tapping a and b activity correlated significantly respectively with BOLD changes in the right motor cortex and bilateral sensory cortices. During rest, activity correlated with BOLD changes in the precuneus (a, b), cingulate (a), middle and superior-frontal gyri (a, b), angular (a, b), supramarginal (a, b), lingual (b) and inferior-temporal gyri (a) and lateral-occipital (a) cortex. Conclusion: Intracranial-EEG-fMRI allowed the investigation of a and b generators and the role played in marking brain networks. Indeed, a and b correlated with BOLD changes which mapped the default mode, fronto-parietal, occipital-visual and occipital-parietal networks and the visual system.

p206 DEFINITION OF A STEREOTACTIC 3D MODEL OF THE HUMAN INSULA FOR NEUROSURGICAL APPROACH (EPILEPSY AND STEREOTAXIC SURGERY) A. Afif*, G. Becq, and P. Mertens* *Neurological Hospital, Hospices Civils de Lyon, Lyon, France; and Grenoble, France
Purpose: Design a method for 3D reconstruction of the insula, including its gyri and sulci, in AC-PC reference usable individually for imaging or for epilepsy and stereotactic surgery. Method: Morphometric study using 100 MRI of normal insular region. 56 male/44 female, 50 left/50 right hemispheres. Stage 1: Reconstruction in AC-PC reference of the insula from 3D-T1-MRI slices 1 mm thick. Stage 2: Digitalization and superposition of data in 3D using PhotoStudio software (Photo Editing Software) system with PC as the center of coordinates. Stage 3 : MATLAB software (Mathworks Inc.) was used to transform in color values each pixel to obtain a color scale corresponding to the probability of insula sulci localization between 0% and 100%. Result: Demonstration of very significant correlations between the coordinates of the main insular structures (angles, sulci ..) and the length of AC-PC. This close correlation allows to describe a method for 3D reconstruction of the insula on MRI slices that requires only the positions of Ac and PC and then the inter-commissural (AC-PC) length. This procedure defines an area containing insula with 100% probability. Conclusion: 3D reconstruction of insula will be potentially useful for: 1 To improve localization of cortical areas, allowing to differentiate insular cortex from opercular cortex during stereoelectroencephalographic exploration of patients with epilepsy (SEEG) or in morphological and functional imaging. 2 For microsurgical approach of Insula using Neuronavigation techniques. 3 Identification of Insula during stereotactic surgery (SEEG, biopsy).
p205 INTRACRANIAL EEG-FMRI: MAPPING BRAIN NETWORKS RELATED WITH ALPHA AND BETA IN SENSORIMOTOR CORTEX S. Perani, S. Vulliemoz, R. Rodionov, L. Lemieux, and D. W. Carmichael UCL Institute Of Neurology, London, UK
Purpose: Alpha (a) and beta (b) are EEG features in the frontal cortex. However, whether alpha and beta originate in spatially independent regions across the sensorimotor cortex and their relationship to different brain networks remain unclear. In this study we used simultaneous intracranial-EEG-fMRI to study local a and b oscillations and map their haemodynamic correlates. Method: One patient with intracranial-EEG (1x57 grid) over the left sensorimotor cortex underwent T1, two sessions of resting-state and one finger-tapping fMRI during simultaneous acquisition of intracranialEEG data. After artifact corrections, electrophysiological signal was time-frequency transformed and averaged into frequency bands. For each frequency band, the power was spatially averaged by taking the first principal component and convolving with a canonical haemodynamic response. Statistical parametric maps of the fMRI changes were obtained
p207 MYOCLONUS CORTICAL GENERATORS IN UNVERRICHT-LUNDBORG DISEASE: AN ELECTRIC SOURCE IMAGING STUDY A. Del Felice*, C. Arcaro*, L. Canafoglia, S. Franceschetti, A. Fiaschi*, and P. Manganotti*
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*Universit degli Studi di Verona, Verona, Italy; and IRCCS Foundation Besta Neurological Institute, Milan, Italy
Purpose: To localize the cortical generator of myoclonic jerks in progressive myoclonic epilepsy (Unverricht-Lundborg disease) applying the Electrical Source Immaging method (ESI). Method: 3 patients (2 female, 1 male, age: 1748 yrs) affected by Unverricht-Lundborg disease underwent a 256channels EEG with concomitant polygraphic recording. Provocative manouvres were conducted during the exam to elicit myoclonic jerks. EEG (electroencephalographic) and EMG (electromyographic) traces were analyzed off line. For the other 2 patients, a back-averaging of the myoclonic EMG activity and corresponding EEG abnormalities was performed. Analysis was conducted off line. A mean of 15 jerk-locked EEG potentials for each patients were averaged, and projected through a LORETA algorithm on an MNI (Montreal Neurological Institute) brain template in order to identify the cortical generator. Result: Jerk-locked EEG potentials were recognizable over the centrofrontal derivations, with a slight lateralization in each single case. ESI elaboration localizes the cortical generator over the anterior premotor frontal cortex (pt 1: Brodman area 6, pt 2: Brodman area 10; pt 3: Brodman area 11), with a lateralization concordant with the EEG potentials (2 right hemisphere, 1 left). Conclusion: ESI is a technique that permits cortical source localization of EEG potentials. Its application to this rare form of epilepsy depicts the important role of the pre-motor and frontal cortex in the myoclonic jerk's generation. To our knowledge, this is the first report describing the cortical source generation from the anterior/premotor cortex. Since only the jerk-locked potential was examined, we can not infer on the involved networks. The level of concordance between fMRI maps derived from the Wave_clus classification and the electro-clinical data was higher for 5 patients compared to the manual classification, and unchanged in the remaining 3. Conclusion: We propose that the use of spike sorting algorithms to classify IED is an efficient tool for mapping the fMRI changes linked to IED, potentially saving time and effort, and increasing the technique's clinical value.
p209 FLUMAZENIL IS A WEAK SUBSTRATE FOR P-GLYCOPROTEIN IN HUMANS. A PET STUDY IN PHARMACORESISTANT PATIENTS WITH UNILATERAL MTS F. E. Froklage*, A. Postnov*, N. H. Hendrikse*, J. C. Reijneveld*, J. J. Heimans*, R. Boellaard*, A. A. Lammertsma*, and R. A. Voskuyl *VU Medical Center, Amsterdam, The Netherlands; and Leiden/Amsterdam Center for Drug Research, Leiden, The Netherlands
Purpose: Pharmacoresistance in epilepsy may be caused by limited drug transport across the blood-brain barrier (BBB) due to increased activity of efflux transporters, such as P-glycoprotein (P-gp). Recent data suggest that flumazenil might be a P-gp substrate. If this is correct, increase in Pgp function in epilepsy could confound the interpretation of results obtained in PET studies with [11C]flumazenil. Method: For this study 10 pharmacoresistant patients with unilateral mesial temporal sclerosis were selected. They were studied twice with [11C]flumazenil, i.e. in the morning and in the afternoon. Before the afternoon scan 2 mg/kg tariquidar (a P-gp blocker) was administered i.v. In 5 patients both [11C]flumazenil scans were preceded by [15O] water scans to measure possible changes in blood flow. Result: Blood flow was not affected. Analysing the [11C]flumazenil data with the one-tissue plasma input model demonstrated a slight increase in distribution volume (VT) from 5.3 0.8 to 5.7 0.3 (p = 0.1, paired t-test). The simplified reference tissue model with the Pons as reference was used to determine BPND. The morning scans demonstrated a BPND of 4.7 1.0 which slightly decreased to 4.2 0.5 in the afternoon scan (p = 0.2). Transfer of the tracer across the BBB was estimated by taking the ratio of VT and 1 + BPND which equals to K1/k2. The K1/ k2 value of 0.92 0.14 increased significantly to 1.1 0.1 (p = 0.003, paired t-test) after the second scan. Conclusion: The significant increase in K1/k2 suggests that flumazenil may be a P-gp substrate. Whether the small decrease in uptake in pharmacoresistant patients is clinically relevant remains to be determined.
p208 A NOVEL METHOD FOR THE CLASSIFICATION OF INTERICTAL EEG ABNORMALITIES IN PARTIAL EPILEPSY: AN EEG-FMRI VALIDATION STUDY A. E. Vaudano*, C. Pedreira, R. Thornton, U. Chaudhary, S. Vulliemoz, H. Laufs, R. Rodionov, R. Quian Quiroga, and L. Lemieux *University of Modena e Reggio Emilia, Modena, Italy; The University of Leicester, Leicester, UK; University College of London Institute of Neurology, London, UK; University Hospital of Geneva, Geneva, Switzerland; and Johann Wolfgang Goethe University, Frankfurt, Germany
Purpose: Scalp recordings and classification of interictal EEG discharges (IED) in patients with epilepsy potentially provide valuable information about the epileptogenic network, particularly by defining the boundaries of the irritative zone, and hence being helpful during presurgical evaluation. Detection and classification of the signals rely in expert observers which can be a time-consuming procedure and presents inter-observer variability. Here, we propose a novel approach: the automatic classification of events using the spike sorting algorithm Wave_clus. This method aims to reduce processing time and provide more objective classification of events. Method: We applied the automatic sorting to the signals collected from EEG/fMRI presurgical evaluation recordings in 8 patients (6 males, mean age: 27) affected by refractory partial epilepsy. For each patient, two fMRI analyses were performed: one based on the visual classification and the automatic IED sorting. All fMRI data were pre-processed and analysed using SPM8. Result: In all cases, BOLD mapping of IED classified with wave_clus reproduced the hemodynamic maps related to the visually labeling. In 7 cases, Wave_clus classification also provided additional fMRI clusters.
p210 ICTAL PET FINDINGS IN PATIENTS WITH REFRACTORY FOCAL EPILEPSY G. Kuester*, S. Marca*, D. Ladron De Guevara*, L. Rios*, F. Solari*, R. Gejman, M. Galvez*, and M. Campos* *Clinica Las Condes, Santiago, Chile; and P.U. Catolica De Chile, Santiago, Chile
Purpose: To present four patients whose PET showed well-localized hypermetabolic foci corresponding to the seizure onset area. Method: Four patients with refractory focal epilepsy studied with Video-EEG monitoring, brain MRI, PET, intraoperative EcoG. Result: Case-1: R. frontal FCD, R. frontal seizures. PET: R. anterior frontal hypermetabolism. Surgery: frontal topectomy. Histopathology:
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type II-B FCD. Seizure free, 24 mo. follow-up. Case-2: R. hippocampal sclerosis, R. mesial temporal seizures. PET: R. hippocampal hypermetabolism, mild/diffuse R. temporal hypometabolism. Surgery: R. anteriormesial temporal resection. Histopathology: type II-B FCD of the end folium of the hippocampus, WM gliosis. Seizure free, 21 mo. follow-up. Case-3: MRI-1: R. occipital FCD, MRI-2: R. anterior temporal FCD. Video-EEG-1: R. temporo-occipital seizures, Video-EEG-2: R. temporal seizures. PET-1: R. occipital hypermetabolism, PET-2: R. anterior temporal hypermetabolism. Surgery 1: R. occipital lobectomy, Surgery 2: R. temporal lobectomy-frontal topectomy. Histopathology: II-A FCD/polymicrogyria. Seizure free, 18 mo. follow-up. Case-4: R. posterior-mesial temporal cavernoma, R. hippocampal sclerosis. EEG: intermittent R. frontotemporal slowing without ictal findings. PET: R. amigdala hypermetabolism. ECoG: continuous ictal/interictal discharges over R. hippocampus/amigdala. Surgery: cavernoma/anterior hippocampus/amigdala resection. Seizure free, 3 mo. follow-up. Conclusion: Interictal PET showing hypometabolic foci is a valuable tool in presurgical evaluation of focal epilepsy. However, correlations of well-localized hypermetabolic abnormalities/histopathology/postsurgical outcomes has not been delineated. In our patients hypermetabolic foci had excellent correlation with seizure onset/histopathology. Hypermetabolic changes could be a signal of very frequent electrographic/subclinical seizures. Although this is a small series and follow up is not long enough, we suggest that ictal PET can provide good information about seizure onset area. Differences in FA of thalamo-cortical and cortico-striatal motor tracts may reflect differences in excitatory and/or modulatory connections, with impacts upon control of voluntary movements and motor learning. Acknowledgement: This research was funded by the Waterloo Foundation.
p212 TEMPORAL POLE ASYMMETRY IN TEMPORAL LOBE EPILEPSY PATIENTS L. Martinkovic*, D. Horinek, O. Bradac, T. Belsan, and P. Marusic *Charles University in Prague, Prague 5, Czech Republic; Marburg, Germany; and Prague 6, Czech Republic
Purpose: The aim was to assess temporal pole volume (TPV) in a group of patients with mesial temporal lobe epilepsy (MTLE) and in healthy controls. Our hypothesis was that TPV asymmetry can distinguish MTLE patients from controls. Method: Fifteen patients diagnosed with refractory unilateral MTLE associated with hippocampal sclerosis (6 right-sided, 9 left-sided) and 30 healthy controls were included. Based on high-resolution MRI left (L) and right (R) temporal pole volumetry was manually performed. The first slice where temporal stem was clearly identified was considered as posterior border. TPV asymmetry was defined by asymmetry index (AI) calculated as 2*(L-R)*100/(L+R). TPVs (ipsilateral vs. contralateral side to the epileptogenic zone) were also compared in MTLE patients. Result: There was high variability in TPV asymmetry in control group (AI 2.4; SD 10.0) and in patients (AI 2.2; SD 17.1). In four MTLE patients only AI was significantly (>2 SD) higher than values observed in controls. In patients TPV ipsilateral to the epileptogenic zone was smaller (17.4 3.7 cm3) than contralateral volume (19.2 3.4 cm3; p < 0.005). Conclusion: There is a high variability in TPV asymmetry both in MTLE patients and in healthy controls. Asymmetry index itself does not allow to differentiate most of MTLE patients from controls. Temporal pole ipsilateral to the side of epilepsy is likely to be smaller in refractory unilateral MTLE patients.
p211 MOTOR CIRCUIT TRACTOGRAPHY PREDICTS MOTOR PERFORMANCE IN CHILDREN WITH ROLANDIC EPILEPSY L. M. Brindley*, F. M. Gibbon, A. Kirby, L. Peters, J. Te Water Naude, M. Thomas, N. Williams, K. D. Singh*, D. K. Jones*, and K. Hamandi *Cardiff University, Cardiff, UK; Cardiff and Vale University Health Board, Cardiff, UK; University of Wales, Newport, Newport, UK; and University Hospital of Wales, Cardiff, UK
Purpose: Rolandic epilepsy, characterised by focal motor seizures, has been associated with motor coordination disorders. This was investigated using the Movement Assessment Battery for Children (MABC-2) and constrained spherical harmonic deconvolution (CSD) tractography in children with rolandic epilepsy. Method: Eight right-handed children with rolandic epilepsy (3 females) aged 912 years completed the MABC-2 and underwent diffusionweighted magnetic resonance MR imaging. Whole-brain CSD tractography was computed and the AAL-labelling atlas warped back into native DWI space for each individual. Partial volume correction for CSF contamination was applied. Mean fractional anisotropy (FA) was assessed for left hemispheric tracts between the following ROIs: SMA; M1; thalamus; cerebellum; basal ganglia. These data were entered as predictor variables in separate stepwise linear regression procedures for each of the age-normalised MABC-2 sub-component and overall percentile scores. Result: MABC-2 scores (mean:18.1, SD:16.9) were variable but significantly below the population mean (t (7)=-5.322, p=.001). Three children scored below the 5th percentile. Higher mean FA of tracts connecting SMA and thalamus predicted better scores upon overall MABC-2 (r=.892, p=.003), manual dexterity (r=.917, p=.001) and balance (r=.968, p<.001). Lower mean FA of tracts connecting basal ganglia with SMA predicted better ball skills (r=-.758, p=.029). Conclusion: Mean FA within specific motor tracts is predictive of motor abilities in a population of children with rolandic epilepsy and variable motor function.
p213 COMPARATIVE VALUE OF SISCOM, FDG-PET AND INTRACRANIAL EEG IN PATIENTS WITH NON-LESIONAL EXTRATEMPORAL EPILEPSY M. Kudr*, P. Krsek*, A. Jahodova*, J. Rybar*, J. Trnka, M. Jaruskova, K. Michalova*, J. Sanda*, M. Kyncl*, J. Zamecnik*, M. Tichy, and V. Komarek* *University Hospital Motol, Charles University, 2nd Medical School, Prague, Czech Republic; Charles University, 1st Medical School, Prague, Czech Republic; Na Homolce Hospital, Prague, Czech Republic; and University Hospital Motol, Prague, Czech Republic
Purpose: To assess a practical value of SISCOM, FDG-PET and intracranial EEG in the localization of the epileptogenic zone in patients with intractable focal epilepsy and normal MRI finding. Method: A group of 14 patients operated on because of intractable epilepsy due to MRI-negative focal cortical dysplasia (FCD) was retrospectively studied. We coregistrated preoperative SISCOM and PET images with postoperative MRI and visually determined whether cerebral cortex underlying the SISCOM focus, PET hypometabolism area and cerebral cortex exhibiting prominent abnormalities on EEG was completely resected, incompletely resected or non-resected. These results and histopathological findings were compared with postoperative seizure outcomes.
64 Abstracts
Result: 13 from 14 patients had a localizing SISCOM. PET findings were normal in three subjects; two of them had favorable postsurgical outcomes. All patients with completely resected SISCOM focus (n = 2), PET hypometabolic area (n = 2) or cortical region exhibiting significant intracranial EEG abnormality (n = 7) had favorable outcomes. By contrast favorable outcome was achieved only in some patients with incompletely (five of nine) or non-resected SISCOM focus (one of two), incompletely (four of seven) or non-resected PET hypometabolism area (one of two) and incompletely resected intracranial EEG abnormality (two of seven). No correlation between histopathological types of FCD and seizure outcome was found. Conclusion: Complete resection of the dysplastic cortex localized by a combination of SISCOM, FDG-PET and intracranial EEG is a reliable predictor of favorable postoperative seizure outcome in patients with intractable non-lesional extratemporal epilepsy. Supported by IGA NT/114435, Kontakt Program ME09042, CZ.2.16/3.1.00/24022 and GAUK 17010. Purpose: Granger causality analysis(GCA) was used to investigate how the temporal epileptic network(TEN) relates causally with other restingstate networks(RSN) and what changes are observed in post-traumatic epilepsy(PTE) patients. Method: This study encompassed 24 healthy subjects and 3 PTE patients. Resting-state fMRI data was acquired in a 1.5T scanner using a BOLD sequence with TR=2 s. Data was pre-processed in DPARSF1.0 software, using a 0.010.073 Hz filter. REST1.6 software was used for GCA based on signed path coefficients(SPC) and order 1. RSN were used as ROI seeds: TEN, comprised of the amygdala, hippocampus and parahipocampus; default-mode network(DMN); sensorimotor network(SMN); visual network(VN); attention network(AN); anterior cingulate(AC), and insula. ROI-wise analysis was done between pairs of networks and voxel-wise analysis was done using TEN as seed. Causal influences between networks were studied in healthy subjects and changes in patients were evaluated using two-sample t-test(p < 0.05). Result: TEN was shown to influence all RSN (positive SPC), with the exception of the VN(probably because a visual stimulus is first processed at the VN before being made available to other networks). The positive causal effect is stronger with the AC, AN and insula, which could translate a stronger influence on cognitive and emotional processes. All patients showed causal changes involving TEN, DMN and SMN, in agreement with known memory and motor impairments. Additional changes were observed in the AN and insula for individual patients. Conclusion: Although preliminary, this study shows GCA as a potential tool to evaluate causal functioning of RSN in PTE patients. In particular, changes were consistently observed in TEN, DMN and SMN.
p214 RELIABILITY OF MEMORY FMRI IN TEMPORAL LOBE EPILEPSY PATIENTS K. Towgood*, A. Caceres*, S. Costafreda*, G. J. Barker*, W. Crum*, R. D. Elwes, M. Mehta*, and M. P. Richardson* *King's College London, London, UK; and King's College Hospital, London, UK
Purpose: Functional MRI (fMRI) of memory functions is emerging as a modality of investigation in presurgical evaluation of mesial temporal lobe epilepsy (mTLE). The reliability and reproducibility of the method is not known. Method: Eighteen subjects with mTLE were scanned over three sessions at intervals of 2 weeks. Each session comprised; (1) Hometown Walk, blocked design; (2) Scenes protocol, block design (Scene Viewing) and event-related design (Scene Encoding); (3) Words and pictures protocol, material-specific blocked designs (Picture Viewing, Word Viewing) and event-related designs (Picture Encoding, Word Encoding). Therefore 7 activation maps were produced per subject per session, 378 datasets in total. We examined between-sessions reliability of activation using intraclass correlation coefficients; the spatial overlap of the anatomical location of activation peaks between sessions; and the ability of each activation map to predict the side of seizure onset. Result: Reliability between sessions 1 and 2 was similar to reliability between sessions 2 and 3. Hometown Walk and Scene Viewing were most reliable (ICCs 70.73 and 64.88 respectively), and Word Encoding least (ICC 30.79). The spatial overlap of the anatomical location of activation peaks between sessions showed similar differences between protocols. Conclusion: We recommend that future evaluations of memory fMRI in mTLE should use two fMRI tasks: Word Encoding, and either Hometown Walk or Scene Viewing.
Paediatric Epileptology 1 Monday, 01 October 2012

p216 SEIZURE BURDEN IN NEONATAL HYPOXIC ISCHEMIC ENCEPHALOPATHY: THE MODIFYING ROLE OF PHENOBARBITONE DURING THERAPEUTIC HYPOTHERMIA N. E. Lynch*, N. J. Stevenson*, B. P. Murphy*, J. M. Rennie, and G. Boylan* *University College Cork, Cork, Ireland; and University College Hospital, London, UK
Purpose: Our aims were to investigate the distribution of seizure burden over time in infants with Hypoxic Ischemic Encephalopathy (HIE) receiving whole-body hypothermia (TH) and to investigate the effect of phenobarbitone (PB). Method: Full- term newborns with moderate and severe HIE, seizures, and continuous video EEG monitoring who received TH were included in this study. All EEG seizures were annotated and the seizure period, defined as the period between the first and last recorded electrographic seizure, the seizure burden per hour and the time-point of maximum seizure burden was identified. Subgroup analysis of seizure burden distribution in moderate and severe HIE was performed. Pearson's correlation coefficient was used to investigate correlation between maximum seizure burden and time of PB administration. A significant correlation between maximum seizure burden and PB administration indicates a reduction of seizure burden after PB. Result: 24 infants were included, 13 with moderate HIE, 11 with severe HIE. Infants with severe HIE had a short period of high seizure burden followed by a long period of low seizure burden (median total period 47.9 hrs). There was no correlation between maximum seizure burden and PB administration. In moderate HIE, there was a shorter total seizure
p215 GRANGER CAUSALITY ANALYSIS OF RESTINGSTATE NETWORKS IN POST-TRAUMATIC EPILEPSY PATIENTS H. A. Ferreira*, A. C. Borralho, P. M. Gonalves-Pereira, R. Manaas, and A. Andrade* *Faculdade de Cincias da Universidade de Lisboa, Lisboa, Portugal; Instituto Politcnico de Lisboa, Lisboa, Portugal; Hospital dos Lusadas, Lisboa, Portugal; and Hospital dos Capuchos, Lisboa, Portugal
65 Abstracts
period (median 11. 3 hrs) and strong correlation between PB administration and maximum seizure period (correlation coefficient= 0.9919; pvalue<0.001). Conclusion: In this study we demonstrate a significant correlation between maximum seizure burden and PB administration in moderate HIE indicating a reduction of seizure burden following PB. This is not seen in severe HIE. Method: All neurologically sick term newborn aEEG records stored since 2004 where no seizures had been seen using standard methods were reviewed using a 60 second view which allowed slow seizures (<4 Hz) to be easily recognized. The final discharge diagnosis in those with and without such seizures were examined. Result: delta frequency seizures were common in neurologically sick infants without higher frequency seizure activity. They were often of relatively low voltage (<25 mcV) but commonly prolonged for over 10 minutes. Conclusion: seizures in the delta frequency are common in sick term neonates although not much described in the EEg literature and not reported in the aEEG literature. At present their prognostic implications are unknown.
p217 IN DEPTH PERFORMANCE ANALYSIS OF A NOVEL AUTOMATED SEIZURE DETECTION ALGORITHM FOR NEONATAL EEG S. Mathieson*, R. M. Pressler, J. M. Rennie*, N. J. Stevenson, L. Marnane, and G. Boylan *University College Hospital, London, UK; Great Ormond Street Hospital for Children, London, UK; and University College Cork, Cork, Ireland
Purpose: Neonatal seizures can be reliably detected with EEG but availability of trained neurophysiologists out of hours is often limited. To facilitate seizure detection for clinical purpose, a novel seizure detection algorithm (SDA) has been developed (Neonatal Research Group, UCC, Ireland). The aim of this study was to introduce a novel neurophysiologybased performance analysis of the SDA in which multiple features of seizures were quantified so as to determine the differences between detected and non-detected groups (by the SDA) and sources of artifact causing false detections. Method: Seizures from 20 neonates were visually annotated and characterised using 10 criteria, including length, frequency change, rhythmicity, peak amplitude, waveform morphology, number of EEG channels involved and background pattern. Seizure annotations from the SDA were compared to those from visual analysis to derive detected and non-detected groups and seizure characteristics were statistically compared. Causes of false detections were determined. Statistical tests included the Mann Whitney U test, Chi Squared and Fisher's Exact Test. Result: There were significant differences between the groups in 9/10 criteria. Detected seizures were longer, more rhythmic, had higher peak amplitude, involved more EEG channels, and had greater frequency and morphology change over the seizure. Certain seizure morphologies were better detected than others. Background EEG had no influence on detection. Primary causes of false detections included respiration, sweat or pulse artefact or a highly rhythmic background. Conclusion: This analysis has identified key areas for SDA modification, which should lead to improved performance.
p219 AMPLITUDE-INTEGRATED ELECTROENCEPHALOGRAPHY AND ELECTROENCEPHALOGRAPHY IN NEONATES W. Kim*, and G. Sim *Chungbuk National University Hospital, Cheongju, Korea; and Cheongju Saint Mary Hospital, Cheongju, Korea
Purpose: Amplitude-integrated electroencephalography (aEEG) allows simplified monitoring of cerebral function and its use for bedside decision-making is increasing. We studied aEEG in a cohort of neonates. Method: We studied 32 neonates who were admitted to our hospital from January 2009 to February 2010. We retrospectively studied EEG, aEEG and brain sonography of neonates who had clinical seizures, apnoea or desaturations. Result: Twenty-two (71.9%) of 32 neonates who had clinical seizures, apnoea or desaturations in the neonatal intensive care unit (NICU) had an aEEG. In the aEEG, 15 (62%) showed seizures, 4 (16%) showed suppression, 5 (20%) showed an abnormality. The correlation between EEG and aEEG was significant (p < 0.005). Of the neonates who had aEEG, 11 (34.3%) had clinical seizures, 22 (68.7%) had apnoea and 21 (65.6%) had desaturations. In patients with abnormal aEEG, the following brain sonography abnormalities were demonstrated: increased periventricular echodensities (41%), germinal matrix hemorrhage (41.1%) and brain swelling (8%). Abnormal aEEG was significantly associated with abnormal sonography (p < 0.05). Conclusion: The correlation of EEG and aEEG in NICU has been demonstrated in this study. Therefore, aEEG monitoring can help with the detection of seizures in neonates.
p218 DELTA FREQUENCY SEIZURES ARE COMMON IN SICK NEWBORNS AND CAN BE EASILY RECOGNISED USING A SIMPLE ADAPTATION TO AMPLITUDE INTEGRATED EEG T. V. Stanley University of Otago Wellington, Wellington, New Zealand
Purpose: Delta frequency seizures were accidentally noted in an infant undergoing routine amplitude integrated EEGs (aEEG) whilst being treated for gram negative meningitis. We elected to discover how commonly electrical seizures in the delta range were recognizable in aEEGs performed in sick newborns where seizure activity had not previously been reported to be present, and to delineate in which newborn conditions they were most commonly seen.
p220 THE APPLICATION OF MULTICHANNEL AMPLITITUDE-INTEGRATED EEG WITH SIMULTANEOUSLY VIDEO EEG IN NEONATAL SEIZURE X. Zhu*, and Y. Wang *Children's Hospital of Fudan University, Shanghai, China; and Shanghai, China
Purpose: To assess the accuracy of amplititude-integrated EEG (aEEG) used to diagnose neonatal seizure, using video EEG (VEEG) as a gold standard, with regard to both the background pattern and the recognition of epileptiform discharges in neonates who have suspected clinical seizures. Method: 66 neonates with suspected clinical seizure were investigated and bedside VEEG was recorded for 3 hours. VEEG signals were transformed into aEEG signals. Background pattern of aEEG and VEEG were
66 Abstracts
analyzed independently and classified. 39 infants with VEEG epileptiform activities (10 s) were investigated, and calculated for single- and multichannel aEEG identified with 1 epileptiform activity. Result: 62 traces were suitable for analysis. A normal background aEEG corresponded with a normal or mild abnormal EEG in 100% of the cases. The PPV for a severely abnormal aEEG (BS, CLV, FT) to correspond with a severely abnormal EEG was 83% (NPV, 96%; sensitivity, 83%; specificity, 96%). On VEEG, 326 epileptiform activities with a mean duration of 78 s were identified. The sensitivity of aEEG for the detection of epileptiform activities was 40% for single-channel aEEG and 51% for multichannel aEEG. Multichannel aEEG identified 95% patients with 1 epileptiform activities, whereas single-channel aEEG (C4C3) identified 82%. Conclusion: CFM is a reliable tool for monitoring both background patterns (especially normal and severely abnormal) and epileptiform activities. Epileptiform detection rate is slightly better with multichannel aEEG compared with single-channel aEEG. We recommend using multichannel aEEG as a monitoring device and performing intermittent standard VEEG whenever there is any doubt about the classification of the aEEG. Purpose: Clinical recognition of neonatal seizures is challenging. Electrographical (EEG) ictal activity have various clinical presentations and electro-clinical Decoupling (ECD) is common after AED. Method: Analysis of video EEGs (30 minutes) recorded before 44 weeks corrected age neonates at risk of or already with suspect seizure disorders. Result: Of 164 consecutive recordings (20072010), 37 neonates (22.5%) had either EEG or clinical events; 7 preterm and 20 (54%) preloaded with AED, 31 had manifest suspect seizures before recording & 6 encephalopathic. 165 EEG seizures were captured in 23 infants, 50 (30.3%) had clinical correlates; 170 suspect clinical events were captured, 120 (70.5%) lacked EEG ictal discharge; 14 (37.8%) babies had only non-ictal events. No relation was relevant between EEG seizure frequency, onset zone, regional or contralateral propagation and the manifest clinical phenomena. 3 EEG seizures less than 10 seconds were associated with subtle events. Mouth twitching was apparent in two cases with ipsilateral Rolandic ictal discharges. EEG seizures were adversely correlated to clinical development (p = 0.045), not the mortality (p = 0.07). Their number was highly predictable of postneonatal seizures (p = 0.003). This was true for number of electro-clinical decoupling (p = 0.025), and captured clinical events (p = 0.001). Conclusion: Most of recognizable suspect clinical phenomena are not genuine seizures. Avoidance of prompt treatment with non-indicated AED on clinical suspicion might prevent unnecessary deleterious developmental iatrogenic effects on growing brain. Despite the poor prognostic implications, probably denoting underlying pathology rather than direct seizure effect, lack of clinical consistency of neonatal seizures might be explained by the immature cortical topographic functional differentiation.
p221 DIAGNOSIS OF NEONATAL SEIZURES: EFFECTIVENESS OF CURRENT CLASSIFICATION SYSTEMS L. Menzies*, H. Cross, and R. M. Pressler* *UCL-Institute of Child Health, London, UK; and University College London, London, UK
Purpose: It is agreed that classification of seizures is important to organizing information for purposes of drug development, clinical and basic research, and of course, clinical practice. In contrast to an agreed and repeatedly updated system for older children and adults (ILAE), at least 3 systems are in use for neonatal seizures with little agreement of their value and practicability. We aimed to assess how well these systems identify and classify neonatal seizures in clinical practice. Method: We identified neonates with seizures form the EEG database at tertiary referral centre (GOSH, UK). Electroclinical, clinical only (no EEG correlate) and electrographic (subclinical) events were classified according to semiology in three classification systems used in clinical practice: Volpe, Mizrahi and ILAE 2010 proposed system. Result: We identified 47 infants (85% term babies) with a total of 285 events (38% electroclinical, 26% clinical, 36% electrographic) and a duration of 857 sec/hour (26% electroclinical, 6% clinical, 68% electrographic). In the Volpe classification 45% of events were classifiable, 18% partially classifiable and 36% unclassifiable, in the Mizrahi classification 77% of events were classifiable, 22% partially classifiable and 1% unclassifiable and in the ILAE classification 41% of events were classifiable, 19% partially classifiable and 40% unclassifiable. Unclassifiable events were mostly electrographic events. Conclusion: Overall the value of classifications was poor: 2 of the 3 classification systems could classify less than half of seizures. This is thought to be due to the high proportion of electrographic seizures and due to the differing seizure semiology in new-born babies.
Semiology, Aetiology and Classification 1 Monday, 01 October 2012

p223 SCREENING FOR SYMPTOMS OF ANXIETY AND DEPRESSION IN PATIENTS WITH PSYCHOGENIC NONEPILEPTIC SEIZURES A. Z. Ilic*, and D. J. Milivojevic *Health Center Studenica, Kraljevo, Serbia; and Medical Centre Petrovac, Petrovac, Serbia
Purpose: Psychogenic nonepileptic seizures (PNES) are somatic manifestations of psychologic distress. This study compared anxiety and depression in patients presenting with psychogenic non-epileptic seizures (PNES) with those suffering from epilepsy. Method: This clinically descriptive, prospective study involved consecutive patients who fulfilled the clinical and video-EEG criteria for PNES and epilepsy, and who were recruited over an 18month period. All subjects were assessed for symptoms of anxiety and depression with Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale. Quality of life was assessed with Sickness Impact Profil. Clinical follow-up was conducted 812 months after the first evaluation. Result: A total of 22 patients were recruited: 11 presented with PNES without epilepsy; and 11 had epilepsy. Both patient groups had similar age, sex and education level. Anixiety and depression values were in 91% and in 54,5% of the ptients with PNES; and in 45,4% and in 18,8% in epilepsy group. Depression and anxiety were increased in PNES group compared to the group with epilepsy and correlated significantly with perceived restrictions due to disease, tolerability and efficacy of drug therapy, financical situation and education, self-efficacy, social support and with the global quality of life. Although seizure control is important
p222 CLINICAL AND ELECTROGRAPHIC PATTERN CORRELATES IN NEONATAL SEIZURES M. M. Awadh*, V. Jain, and M. E. ORegan *Ain Shams University Hospitals, Cairo, Egypt; and Royal Hospital for Sick Children, Glasgow, UK
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in both disorders, seizure remission is not a comprehensive measure of good outcome in PNESs. Conclusion: The prevalence of anxiety and depression in PNES group is considerably higher than in the epilepsy group. Seizure control should not be the only focus of treatment in PNES patients and should be complemented by appropriate psychiatric and psychological care. ences in the numbers of somatic symptoms of arousal between the two groups, particularly occurring during the recent seizure, which otherwise tended to be higher in the DS group. Of particular interest, the DS patients reported higher levels of cognitive symptoms of panic after, rather than during, either their most recent or ever experienced seizures than did the ES group; for both time periods anxiety was a significant predictor of symptom number. Conclusion: Anxiety level was a significant predictor of seizure-related autonomic and somatic symptoms that appear to differentiate between DS and ES patients. Evidence of more extensive negative cognitive interpretations following DS seizures, even after adjusting for anxiety levels, suggests that negative seizure-related cognitions are particularly characteristic of DS patients, may serve to maintain the disorder and should be addressed in cognitive behavioural therapy.
p224 PSYCHOGENIC NONEPILETIC SEIZURES IN VIDEOEEG MONITORING UNIT: SPONTANEOUS SEIZURES AND EFFECTIVITY OF PROVOCATIVE TECHNIQUE I. Mareckova, Z. Vojtech, T. Prochazka, and L. Kramska Na Homolce Hospital, Prague, Czech Republic
Purpose: To evaluate the effectiveness of provocative technique in patiens with psychogenic nonepileptic seizures (PNES). Method: We reviewed medical records of 1378 patients with pharmacoresistant seizures who underwent long term (57 days) video-EEG monitoring at tertiary care epilepsy center from January 2000 to December 2011. All patiens underwent routine evaluation (video-EEG, brain MRI and complete neuropsychological examination). In patiens who had not had spontaneous seizures we used suggestion and intravenous saline injection. Result: We identified 231(17%) patients with various types of PNES without background of epilepsy. There were 154 (67%) women and 77 (33%) men. 81(36%) patients had their habitual seizure spontaneously, 64 (42%) of women compared to 20 (26%) of men. 110 (49%) patients were induced. In 98 (89%) of them the procedure was diagnostic, 67 (44%) women and 31 (40%) men. In 12 (11%) the procedure was negative. In 23 (10%) patients the diagnosis of PNES was based on a clinical history. 12 (5%) of patients signed negative revers. Conclusion: Our results proved a high effectiveness of suggestive seizure provocation. Considering controversies of this technique we are convinced about its usefulness as only a minority of patiens had their spontaneous seizures during video-EEG monitoring. Delayed diagnosis could lead to iatrogenic complications, is costly to patients, the health care system and society. It is obvious that correct diagnosis is neccessary to prevent these consequenses.
p226 THE ROLE OF ELECTROENCEPHALOGRAPHY IN DIAGNOSTICS OF CENTRAL NERVOUS SYSTEM (CNS) STRUCTURAL LESIONS IN CHILDREN WITH MINOR NEUROLOGICAL SYMPTOMS O. Kozhevnikova, O. Klochkova, O. Logacheva, L. NamazovaBaranova, and A. Anikin Scientific Centre of Children Health, Moscow, Russian Federation
Purpose: to assess the possibilities of electroencephalography (EEG) in detecting the structural lesions of CNS, to evaluate its correlation with magnetic-resonance imaging (MRI) findings in children with minor neurological symptoms. Method: 182 children (7 months 18 years old) with minor neurological symptoms underwent video-EEG on digital electroencephalography machines Bravo NicOne (Nicolet, USA). All children under 3 years and some after 3 years underwent EEG during the day sleep. Patients main complaints included headaches (27%), single or first episode of seizures (25%), hyperexcitement (14%), fatigability (13%), syncopes (10%). All children had pathology according to perinatal anamnesis. Brain MRI's were done on Signa Twin speed Excite 1,5 T1 Tomography Machine (GE, USA). Result: 163 (89,6%) children with minor neurological symptoms and minimal changes on EEG had alterations of structure or/and brain vessels according to MRI. 140 patients (76,9%) had pathological changes on EEG accompanied by structural changes on MRI, herewith 36 children (26%) had angiopathy. Among structural disorders dominated local subatrophy and ventriculomegaly 23 (12,6%) patients with EEG disorders had only vessels deviations (S-shape deformation of internal carotid artery (ICA), flexura of ICA or vertebral artery (VA), hypoplasia of VA and combination of hypoplasia and deformation of ICA and VA, narrow ICA). Conclusion: We recommend to analyse the EEG in children under 3 years only during the sleep and send children with EEG changes to MRI investigation in the following cases: 1) minor local disorder or resistant lateralization of changes in routine EEG; 2) pathological EEG with hypersynchronization of b or h rhythms, disorganized EEG with absent or decreased a-rhythm;3) paroxysmal types of EEG in children of any age, even with no pathology in wakeful state.
p225 COGNITIVE AND SOMATIC SYMPTOMS OF ANXIETY DURING DISSOCIATIVE AND EPILEPTIC SEIZURES L. H. Goldstein*, R. S. Delamont, and J. D. C. Mellers *Institute of Psychiatry, King's College London, London, UK; King's College Hospital NHS Foundation Trust, London; and South London & Maudsley NHS Foundation Trust, London, UK
Purpose: To extend our previous investigations of the presence of anxiety-related seizure symptoms in adults with dissociative (psychogenic nonepileptic) seizures (DS) compared to partial epilepsy patients (ES). Method: 28 DS and 35 ES patients, without comorbid panic disorder, were recruited from an inpatient videoEEG telemetry unit. Within 36 hours of a seizure, patients completed questionnaires indicating the presence or absence (before/during/after that seizure or ever related to a seizure) of epilepsy-related symptoms and somatic or cognitive symptoms of anxiety, particularly panic. Measures of anxiety and depression were also completed. Result: Unlike our previous study, DS patients had significantly higher anxiety and depression scores than the ES group. Adjusting for anxiety (as well as duration of seizure disorder) reduced between-group differ-
p227 PREVALENCE OF RESTLESS LEGS SYNDROME AMONG ADULT EPILEPSY PATIENTS IS HIGH: A PRELIMINARY SCREENING IN ARMENIA S. Khachatryan*, Y. Tunyan*, L. Ghahramanyan, and T. Stepanyan
68 Abstracts
*Yerevan State Medical University, Yerevan, Armenia; Somnus Sleep Disorders Clinic, Yerevan, Armenia; and Erebouni Medical Center, Yerevan, Armenia
Purpose: To perform a preliminary screening of restless legs syndrome (RLS) among adult patients with epilepsy in Armenia. Method: The screening has been performed among consecutive patients attending Armenian Republic Epilepsy Center Erebouni. Only adult patients aged 18 and above with definite epilepsy diagnoses (both de novo and chronic) were included. The four essential criteria to diagnose RLS proposed by International RLS Study Group (IRLSSG 2003) have been used by a trained clinician-researcher team. Only patients positive for all four criteria have been considered to have a clinically significant RLS. Additional brief interview has been conducted to exclude other possible mimics of RLS. Assessment of RLS severity and form (idiopathic or symptomatic) was not a purpose of this screening. Descriptive statistics was used for evaluation. Result: Eighty one out of the 93 patients screened had confirmed allcause epilepsy diagnoses (n = 81). They had 1864 age interval (mean age 32.1, 37 females 45.7%). We found 10 patients fulfilling all 4 criteria for RLS (12.3%), and among them 6 males and 4 females (accordingly m:f = 60%:40%). RLS in females was 10.8%, and in males 13.6%. Our previous telephone survey (Khachatryan et al. Sleep Medicine 2007) showed 7,9% prevalence of RLS in general adult Armenian population and higher prevalence in males. Conclusion: We found high prevalence of RLS in Armenian epilepsy patients. It was found higher among males. As a sleep restricting and disrupting factor, RLS could contribute to difficulties in the management of epilepsy patients and thus should be screened for carefully.
p229 HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH EPILEPSY, NON-EPILEPTIC ATTACK DISORDER AND DUAL DIAGNOSIS F. Ali*, and A. E. Cavanna *Birmingham and Solihull Mental Health NHS Foundation Trust, Birmingham, UK; and Institute of Neurology, London, UK
Purpose: Little is known about the differential impact of epilepsy and non-epileptic attack disorder to patients health-related quality of life (HR-QOL). In this study, we sought to compare self-reported HR-QOL in patients with epilepsy, NEAD and dual diagnosis. Method: We recruited a total of 66 adult out-patients (n = 17 with a diagnosis of epilepsy, n = 34 with NEAD and n = 15 with a dual diagnosis) from the specialist Neuropsychiatry Clinic at BSMHFT/University of Birmingham. Each participant completed a standardised psychometric battery which included the Quality of Life in Epilepsy-31 (QOLIE-31). Result: We found significant differences in cumulative HR-QOL scores (Kruskall-Wallis test, p = 0.041) across the three groups. Patients with dual diagnosis demonstrated poorest HR-QOL ratings (mean=28.4), followed by NEAD (mean=30.7) and epilepsy (mean=43.5). The most significant differences were in the Emotional Well-Being domain (p = 0.008), where patients with dual diagnosis reported the lowest scores (mean=28.9), followed by NEAD (mean=29.3). Patients with epilepsy reported considerably higher HR-QOL in this domain (mean=45.9). Conclusion: Patients with a dual diagnosis of epilepsy and NEAD report poorest cumulative HR-QOL, with significantly lower scores on Emotional Well-Being. Future investigation should be targeted to elucidate causal links between specific ictal and inter-ictal variables and HR-QOL subdomains.
p228 CO-EXISTING PSYCHOGENIC NON-EPILEPTIC SEIZURES AND EPILEPTIC SEIZURES: DETERMINATION OF INCIDENCE IN AN EPILEPSY MONITORING UNIT POPULATION D. F. Thomas, and A. Krumholz University of Maryland Medical Center, Baltimore, USA
Purpose: It is well described that psychogenic non-epileptic seizures (PNES) and epileptic seizures (ES) may co-exist in the same patient, but how to best define this co-existence and its incidence are debated. Method: We reviewed all epilepsy monitoring patients at the University of Maryland Medical Center and Veterans Administration Medical Center Baltimore over an 18 month period to assess the incidence of both PNES and ES co-existing in the same patient as documented by capturing both PNES and ES during the same admission. Patients who had more than one admission were counted only once. Result: Of our 272 total epilepsy monitoring patients, 172 (63%) were female, and the mean age was 41 years (range 1688, standard deviation 14.6). Of the total patients, 74 (27%) had documented PNES during their admission, and 11 (14.9%) of these PNES patients had co-existing epileptic seizures determined by video EEG during that same admission. Conclusion: The percentage of co-existing PNES and ES captured on video EEG monitoring in our patients (14.6% of all PNES patients) was higher than expected, and may relate in part to more aggressive seizure medication tapers to provoke events, thereby unmasking more epileptic seizures in our patients. In addition, embellished auras mimicking PNES cannot absolutely be ruled out in a small number of cases. Still, the incidence of co-existing PNES and ES in such a high percentage of patients is notable and suggests that caution is warranted when tapering medication in some patients with PNES.
p230 DISSOCIATIVE EXPERIENCES AND QUALITY OF LIFE IN PATIENTS WITH NON-EPILEPTIC ATTACK DISORDER J. W. Mitchell, F. Ali, and A. E. Cavanna Birmingham and Solihull Mental Health NHS Foundation Trust, Birmingham, UK
Purpose: A wide range of dissociative experiences have been reported in clinical samples of patients diagnosed with non-epileptic attack disorder (NEAD). This study investigated the possible impact of dissociative experiences on health-related quality of life (QOL) in this patient population. Method: In this cross-sectional study we consecutively recruited 37 patients (67% female; mean age=44, sd=13.7) with a diagnosis of NEAD from a specialist neuropsychiatry clinic. Nine patients (24.3%) had concomitant epilepsy (dual diagnosis). Clinical diagnoses were validated by neuroimaging and neurophysiology findings. Result: Our sample reported a high level of dissociative experiences, with a mean score of 24.9 (sd=18.2) on the Dissociative Experiences Scale (DES). We found no significant differences in DES scores between patients with NEAD and patients with a dual diagnosis (Mann-Whitney U = 117.5, p = 0.884). There was significant negative correlation between DES scores and QOL, as measured by the QOLIE-31 inventory (n = 35: Pearson's r=-0.664, p < 0.01). This association remained significant when accounting for measures of depression (Beck Depression Inventory, BDI) and anxiety (Spielberger State-Trait Anxiety Inventory, STAI). A multiple regression analysis model accounted for 73.6% of the variation in total QOLIE-31 scores (n = 33: adjusted R square=0.736). Total DES scores accounted for 52.5% of the variance, whilst the BDI and STAItrait scores accounted for 16.6% and 4.5%, respectively.
69 Abstracts
Conclusion: These findings confirm previous reports of high prevalence of dissociative experiences in clinical populations with NEAD and highlight the importance of routinely screening patients for these symptoms. The strong association with QOL suggests that patients with NEAD would benefit from treatment interventions targeting dissociation. be placed on the new waiting list. 10 patients passively declined to be placed on the waiting list due to non-responding. A total of 19 patients requested a triage appointment. Of these, patients, 7 were assessed and discharged, 6 were assessed and a treatment plan was formulated and 6 were reviewed and referred to local mental health services with a review planned. Conclusion: The development of this waiting list initiative and triage clinic has resulted in a reduction in waiting list size. Furthermore, patients who are referred to this clinic now receive an initial appointment within three months following inpatient review. Results will be discussed with respect to the pro's and con's of approaches to waiting list management.
p231 MUTATIONS WITHIN THE GLRA1 GENE ASSOCIATED WITH HYPEREKPLEXIA S. E. Wood*, S. Ali*, C. Drew*, O. W. Howell*, R. H. Thomas, M. I. Rees*, and S. Chung* *Swansea University, Swansea, UK; and Wales Epilepsy Research Network, Swansea, UK
Purpose: Hyperekplexia is a paroxysmal neurological disorder caused by defects in glycinergic neurotransmission and is characterized be exaggerated startle reflexes and hypertonia in response to sudden, unexpected auditory or tactile stimuli and in some instances, can result in life-threatening infantile apnoea episodes. This rare, but potentially fatal, neurological disorder is associated with mutations in genes encoding the a1 (GLRA1) and b (GLRB) subunit of the glycine receptor and the presynaptic glycine transporter GlyT2 (SLC6A5). Method: As part of an ongoing screening program, we have analysed the entire coding regions of GLRA1 in 66 patients referred to our screening project. All sequence variants identified were regarded as mutations after exclusion from a panel of human controls and assessed for protein damaging outcomes with molecular modelling. Result: Direct sequencing analysis revealed 15 GLRA1 variants including 11 non-synonymous changes, 3 nonsense and a recurrent large deletion of exon 1 to 6; eight variants identified were novel and not in the public domain. Recessive inheritance was revealed in 13 cases, including 2 cases of compound heterozygote inheritance, and a dominant inheritance in 3 cases. Consistent with previous studies, all deletion and nonsense mutations were associated with recessive onset of phenotype, whereas missense mutations could exert dominant or recessive influences depending on the position of the mutation in the polypeptide. Conclusion: Identification of novel mutations in this study increases the compendium of GLRA1 mutations in the diagnostic domain for hyperekplexia and promote further work into the pathophysiological mechanisms underlying the ancient startle response.

p233 A RETROSPECTIVE STUDY OF 131 PATIENTS WITH PSYCHOGENIC NON-EPILEPTIC SEIZURES (PNES): COMORBID DIAGNOSES AND OUTCOME AFTER INPATIENT TREATMENT H. C. Miersch, K. Bohlmann, and H. Straub Epilepsieklinik Tabor, Bernau, Germany
Purpose: This retrospective study analyses the comorbid diagnoses of patients with psychogenic non-epileptic seizures (PNES) and the outcome after in-patient treatment including cognitive behavioural therapy, family therapy and non-verbal therapies. Method: Within 7 years 377 in-patients were treated in the department for epileptology and psychotherapy of the Epilepsiezentrum Berlin-Brandenburg. 131 patients were diagnosed with PNES. All diagnoses reported at the time of discharge were reviewed. Follow-up interviews of 111 patients were made within 6 months after discharge. Result: Comorbid somatic diagnoses were found in 42 patients. 64% were related to the brain. Concomitant epilepsy was confirmed in 31 patients. Comorbid psychiatric diagnoses were anxiety disorders (47), personality disorders (41), posttraumatic stress disorder (39), substance abuse(14), depressive disorders (11), somatoform disorders (6), bipolar disorder (5), factitious disorder (4), Asperger syndrome (3) . Psychic traumas were found in the history of nearly all patients. Sexual assault was reported by 28 patients and strongly suspected for another 21 patients. 89 patients complained about massive and long running conflicts within their families. After in-patient treatment 57 patients remained free of seizures. 36 patients had less frequent seizures, 17 were unchanged, 1 had committed suicide. Conclusion: In-patient treatment including intensive psychotherapy and additional non-verbal therapies in a clinic with an expertise in epileptology, psychiatry and psychotherapy is successful for nearly 3/4 of patients with PNES. Beside sexual assault 68% of the patients with PNES reported severe and longlasting conflicts in the family causing psychological distress. This confirms the importance of family therapy besides cognitive behavioural therapy.
p232 DEVELOPMENT OF A WAITING LIST INITIATIVE AND IMPLEMENTATION OF AN EARLY INTERVENTION CLINIC FOR NON-EPILEPTIC ATTACK DISORDER G. M. Fortune, J. A. Magee, and C. Brien Beaumont Hospital, Dublin, Ireland
Purpose: To develop a waiting list initiative and early intervention outpatient clinic for patients with non-epileptic attack disorder to reduce waiting list times and improve access to psychological treatment. Method: A waiting list analysis was conducted (n-64). An opt-in system was then introduced. Patients who opted-in received a 30minute triage appointment to review their case and plan towards further intervention where necessary. Standardised intake measures and patient satisfaction data were obtained. Result: Following waiting list analysis, 47 patients were entered into the opt-in system. Those patients who opted in, all received a triage appointment resulting in a treatment contract or a discharge to local services. Following an invitation to opt-in, 18 patients actively declined to
p234 SIGNIFICANCE OF ACTIVATION OF AURAS IN PATIENTS WITH PSYCHOGENIC NON-EPILEPTIC SEIZURES (PNES) K. N. Ramesha, A. Ribeiro, D. Amin, and F. Brunnhuber Kings College Hospital, London, UK
Purpose: To evaluate the significance of activation of habitual auras in the activation clinic in patients with suspected PNES.
70 Abstracts
Method: We studied consecutive 105 patients, confirmed to have PNES in our activation clinic over the last five years. The diagnosis of PNES was made based on electro-clinical features of the recorded event(s). They were confirmed to be habitual by patients and/or their eyewitnesses. Result: The mean duration of PNES before the activation clinic was 9.7 years (range: 156 years). Suggestions alone brought out habitual PNES in five patients, photic stimulation alone was used as an induction procedure in 49 and combination of photic stimulation and hyperventilation was used in another 20 patients. No active activation procedure was performed in 15 patients and various combinations of the above procedures were used in the remaining. 41 patients reported their habitual aura in the activation clinic. They were epigastric aura (n = 6), olfactory aura (n = 2), gustatory aura (n = 4), visual aura (n = 1), auditory (n = 2), sensory (n = 5) and nonspecific auras (n = 23). No statistically significant correlation was noted between the presence of aura and duration of PNES. Conclusion: Auras that are commonly regarded as epileptic auras do occur as dissociative auras in PNES during activation and thus do not imply the coexistence of epilepsy. Activation of epileptic auras in the activation clinic appears to be a strong point in favour of the diagnosis of PNES. Purpose: Both epileptic seizures (ES) and psychogenic non epileptic seizures (PNES) can coexist in the same patient. According to published data, between 8 and 60% of patients with PNES also can have ES. Longterm videoEEG (LTVE) is the diagnostic tool used to differentiate them. But it is not well established how long LTVE should be to make a proper diagnosis in these cases. Objetive: To describe clinical and LTVE features in patients with both ES and PNES admitted in Epilepsy Unit (EU) and estimate LTVE duration to make diagnosis. Method: We reviewed LTVE, medical history and complementary tests in 94 adult patients admitted in our EU between 2010 and 2011. We divided them into 3 groups: patients with only ES, only PNES and both ES+PNES. We compared them. All the episodes were checked with the family. Result: 84 patients had seizures. 62 had only ES, 16 PNES and 6 both ES+PNES. Non statistically significant differences were found between time of appearance (TOA) (days) of PNES and ES groups, median 2 (1 3) vs 3 (14), p 0.63. In ES+PNES group, ES TOA was 3.5 (2,54,25) vs PNES 2 (1,753,25). All patients in ES+PNES group had PNES first. 83.3% of them had the first ES after the second day. In our study, 27% with PNES had also ES. Patients with both ES+PNES had first PNES during monitoring. An early monitoring disruption could lead to a misdiagnosis in this group. A prolonged LTVE (>72 hours) to record both episodes is justified and necessary to make a correct diagnosis.
p235 USE OF ANTI-EPILEPTIC DRUGS IN THE SETTING OF NON-EPILEPTIC SEIZURES M. Stefanidou, S. Nadkarni, and C. Carlson New York University, New York, USA
Purpose: Non-epileptic seizures (NES) without concurrent epilepsy account for about 10% of patients evaluated in epilepsy monitoring units. Many of these patients are on anti-epileptic drugs (AEDs) upon admission for their events and/or co-morbid psychiatric and pain disorders. We evaluated if presence of AEDs at the time of diagnosis of NES affects their long term exposure to these agents, given concerns of unnecessary use of AEDs in this patient population. Method: A retrospective review of all admissions to the epilepsy monitoring unit at NYU for 2010 was conducted. Inclusion criteria required capturing the targeted event and a normal video-EEG. AEDs and other psychotropic agents were recorded upon initial admission, discharge, and at follow up. Result: Of 900 patients, 75 (8%) patients were diagnosed with NES with 44 (60%) on AEDs upon admission. The most prevalent co-morbid psychiatric conditions were anxiety, mood and panic disorders without significant difference between patients on or off AEDs at admission (p = 0.73). AED use at admission correlated with higher use of AEDs at discharge (p = 0.0001). 70% of patients had outpatient follow-up. Patients on AEDs at admission were more likely to be on AEDs at follow-up (p = 0.0001) and use these agents for treatment of concurrent psychiatric and/ or pain conditions (p = 0.02). Conclusion: Presence of AEDs upon admission for evaluation of NES increases probability of long term exposure to AEDs. Although this study does not compare clinical outcomes, it suggests a possible benefit from early evaluation of events prior to the initiation of AEDs in patients with high suspicion for NES.
p237 RINCH MOTIONS (RHYTHMIC ICTAL NONCLONIC HAND MOTIONS) ANALYSIS: INCIDENCE AND LATERALIZING VALUE K. Musilov*, R. Kuba*, N. M. Vojvodic, M. Brzdil, I. Tyrlikova, and I. Rektor *Brno Epilepsy Centre St. Anne's University Hospital and Faculty of Medicine, Brno, Czech Republic; Clinic of Neurology Clinical Center of Serbia, University of Belgrade School of Medicine, Belgrade, Serbia; Epilepsy Center Brno, St. Anne's University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic, Brno; and St. Anne's University Hospital and Faculty of Medicine, Masaryk Univerzity, Brno, Czech Republic
Purpose: The principal aim of this retrospective study was to analyse occurrence and lateralizing value of Rhythmic Ictal Nonclonic Hand (RINCH) motions symptom in temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) or with other lesion of temporal lobe (TLE-oth) in our group of patients. Method: Retrospectively, we analysed 120 patients with temporal lobe epilepsy (TLE). All patients were classified as Engel I at the 2year follow-up visit. Histopathological examination revealed hippocampal sclerosis (TLE-HS) in 70 patients and other lesions in 45 patients (TLE-oth); 5 patients had no lesions. We reviewed 491 seizures. RINCH motions were defined as unilateral, rhythmic, nonclonic motions occurring during the seizure, sometimes in the relation to the dystonic posturing of the hand on the same side. Result: RINCH motions were observed in 24 of 120 patients (20%), and in 48 of 491 seizures (9.8%). There was no significant difference between occurrence of RINCH motions in patients with TLE-HS and in patients with TLE-oth (21.4% vs. 18%). RINCH motions were contralateral to the seizure onset in 83.3% of patients, and in 91.7% of seizures. RINCH motions were more frequent in patients with left- than right-sided TLE (68.63% vs. 31.37%) and they were associated with dystonic posturing on the affected side in 33.33%. There were no differences in lateralizing value of RINCH motions between patients with TLE-HS and TLE-oth.
p236 CLINICAL AND LONG-TERM VIDEOEEG FEATURES OF PATIENTS WITH BOTH PSYCHOGENIC NON EPILEPTIC AND EPILEPTIC SEIZURES: A PROSPECTIVE STUDY IN A SPANISH EPILEPSY UNIT R. M. Vivanco-Hidalgo, J. Jimenez-Conde, A. Massot, J. Herraiz, C. Garcia-Ribera, J. Roquer, and R. Rocamora Parc de Salut Mar-Hospital de Mar, Barcelona, Spain
71 Abstracts
Conclusion: RINCH motions symptom is a relatively frequent ictal sign in patients with TLE. The side of RINCH motions in patients with TLE lateralizes the seizure onset to the contralateral temporal lobe. Aknowledgements: This work was supported by MSMT CR research project MSM0021622404. coinciding with reduced epilepsy admissions. Outpatient interventions have increased. The number of telephone contacts have more than doubled in the second year, appearing static in years three and four. Educational and supportive visits to the child's home and school have also increased. Activities of an ESN changes over time towards non-admission and community-based activity.
p238 WHAT ABOUT A TRANSITION PROGRAM ON EPILEPSY? J. Carrizosa, and T. Rodriguez University of Antioquia, Medelln, Colombia
Purpose: Transition from a family to an individual centered service, could carry troubles for persons with chronic diseases. General guidelines from IBE and ILAE are lacking. The purpose is to built up a transition reference guideline for persons with epilepsy. Method: Literature review; questionnaires on transition during the VI Latin American Congress in Cartagena. Framework on goals and key topics. Result: Goals: 1. Preparing adolescents and young adults for transfer of care 2. To provide uninterrupted health care 3. Education on specific and individual issues 4. To promote self advocacy skills and independence 5. To optimize quality of life, life expectancy and future productivity. Key points: 1. Timing of transition and transfer 2. Family Dynamics 3. Health Supervision Issues 4. Anticipatory Guidance 5. Sexuality, Reproductive Issues and Pregnancy 6. Genetic Counseling 7. Education and Degree Choices 8. Physical Activity Sports 9. Drivers Licence 10. Mortality 11. Psychiatric Aspects 12. Medical Social Insurances. Conclusion: A transition program, with prepared communication between pediatric -adolescent and adult health services, could foster a better quality of life in persons with epilepsy.
p240 IMPLEMENTING THE AMERICAN ACADEMY OF NEUROLOGY EPILEPSY QUALITY MEASURES USING AN EPILEPSY ELECTRONIC PATIENT RECORD AS A TOOL FOR CHANGE M. Fitzsimons, B. Dunleavy, P. OByrne, and N. Delanty Beaumont Hospital, Dublin 9, Ireland
Purpose: The American Academy of Neurology (AAN) quality indicators for epilepsy care describe the tasks that should be performed during a patient encounter and specify details to be documented in the medical record. With these, quality of epilepsy care can be monitored, gaps identified and ultimately improvements made. Aim: An epilepsy electronic patient record (EPR) was used to implement AAN quality indicators to assess performance of an out-patient service. Method: A sample of out-patient clinics at Beaumont Hospital, Dublin was assessed. The epilepsy EPR was examined to determine if it supported the capture of data relevant to four AAN indicators of interest. Using a specialised database query language, structured and unstructured data fields were interrogated to generate the numerator and denominator for the indicators. Result: Over a sample of 5 weekly out-patient clinics there were 161 individual patient encounters. Of these 87% (142/161) conformed with the requirement to document seizure type and seizure frequency at each visit (indicator 1); etiology or epilepsy syndrome was documented/ updated for 57% (93/161) (indicator 2); evidence of querying and counselling about anit-epileptic drug side-effects for that encounter was present in 30% (49/161) of records. Over a 1 year period, counselling for women of childbearing potential (indicator 8) was present in 30% (102/ 346) records. Conclusion: Feasibility of the epilepsy EPR for efficient performance monitoring was demonstrated. Results indicate either failure to carryout recommended clinical tasks or poor documentation. Whichever is the case, a baseline is provided against which improvement goals can be set.
p239 A REVIEW OF AN EPILEPSY NURSE SPECIALIST'S CLINICAL ACTIVITY & ASSOCIATION WITH PAEDIATRIC EPILEPSY ADMISSIONS K. Johnson*, and C. Dunkley *Kings Mill Hospital, Nottinghamshire, UK; and Sherwood Forest Hospitals, Sutton in Ashfield, UK
Purpose: To quantify and characterise clinical activity for the ENS over time and to assess whether the introduction of an ENS is associated with a change in paediatric epilepsy admission rates. Method: A prospective review of the ENS diary was undertaken documenting all client contact. Activity was collated comparing the types of client contact over a 4 year period 20072011. Local admission rates of children with epilepsy were also obtained using the Child and Maternal Health Observatory (CHIMAT) Data Atlas which maps Hospital Episode Statistics (HES) data to geographical areas. Result: The prospective diary review showed a yearly median of 29 ward visits; 2 Emergency Department visits, 35 home visits; 560 telephone contacts; 15 Buccal Midazolam training sessions and 32 ad-hoc paediatric outpatient reviews, Each year there was a median of 22 multidisciplinary epilepsy clinics; 19 nurse led clinics; 4 paediatric neurology clinics and 71 school visits. Mean admission rates over 3 years before the ESN commenced were 67/100,000 children/year (range 6272.1). Mean rates over 3 years after ESN commencement were 35.2/100,000 children/ year (range 32.337.5). Conclusion: The diary review clearly shows the diversity of the ENS activity and how this has changed over time. Ward visits have reduced
p241 TRANSITION'S GAP FROM PAEDIATRIC TO ADULT SYSTEM CARE OF PATIENTS WITH EPILEPTIC ENCEPHALOPATHY: A MYTH OR A REALITY? M. Kuchenbuch*, N. Chemaly*, C. Chiron, O. Dulac*, and R. Nabbout *Necker, Paris Cedex 15, France; and Inserm, Paris, France
Purpose: In order to understand the reality of a transition gap between pediatric and adult care system in patients with epileptic encephalopathy, we compared medical care between childhood and adulthood with a detailed description of factors that impacted the transition in a cohort of patients with Dravet syndrome. Method: 52 surveys realized by a group of experts with help of IPSOS institute and Wyeth foundation were filled by patients and families with Dravet syndrome, aged over 18 years. Student t-tests and fisher exact tests were used. After validity conditions verification, we compared the experience of patients and their family in paediatric versus adult care system and then we studied the factors that impacted the quality of transition.
72 Abstracts
Result: Sixty one percent had a transition and 92% of them noted that there wasn't any gap during their transition to adult care. Factors that positively impacted their transition were the transition preparation quality (p<.000001), longer duration of follow-up in the same pediatric structure (p<.001), good availability of the pediatric staff (p<.01), age over 18 years at transition (p<.01) and good health's condition before transition (p<.05). All families had a positive experience in paediatric health system. Paediatricians were considered as welcoming, taking time to explain and helping. Contrarily to the impression of child neurologist, the adult care system experience was identical and showed no statistical difference. Conclusion: Transition in Dravet's syndrome showed a lack of gap between pediatric and adult care health system. the hospitalization. For over 10 years, there has been a patient education program primarily for parents at the department. The teaching has been organized from a commonsense approach without any genuine formalized educational goals, and without any proven pedagogical approach to learning. In order prospectively to reinforce patient education in the department, this project started August 2011 and will be concluded in August 2014. Method: The study is a combination of observation and interview studies where interviews are conducted with teachers, parents, children in a pediatric ward in Denmark and Norway. The purpose of the study is to compare the learning environment in Denmark and Norway. Result: Aim: To explore how children learn mastering the everyday life with epilepsy during hospitalization. The project deals with children with epilepsy and there learning processes during hospitalization. The project takes a broad life history as well as cultural and social view on the learning processes. Parents have a central role in patient education at the ward, and the purpose of the study is to bring an analytical look at the learning environment, understood as the interaction between the department, teacher and patient. Conclusion: Research questions: How do children learn to live with epilepsy with all its consequences for the individual's everyday life? Which learning processes imply the everyday life with epilepsy and in which way does it appear in the learning environments at the paediatric department?
p242 AUDIT OF PATIENT SATISFACTION AT THE TRANSITION ADOLESCENT EPILEPSY CLINIC IN THE WALTON CENTRE NHS FOUNDATION TRUST, LIVERPOOL M. Rodriguez*, T. Marson*, and R. E. Appleton *Walton Centre for Neurology and Neurosurgery NHS Foundation Trust, Liverpool, UK; and Alder Hey Children's Hospital, Liverpool, UK
Purpose: We assess the satisfaction of patients attending the Transition Adolescent Epilepsy Clinic at the Walton Centre, a monthly clinic run jointly by an adult and a paediatric neurologist. Method: A Patient Satisfaction Questionnaire was sent to 108 patients (new or follow up) who attended the clinic between March 2009 and September 2010. Result: Questionnaires were returned by 30 patients (response rate 27%), 16 were female, age range 1822. 11 had focal, 4 generalized and 4 unclassified epilepsy. 21 had experienced seizures within the preceding 12 months. 29 patients were receiving an antiepileptic drug, of whom 15 were on monotherapy. Regarding the handover, 53% stated that they were told what to expect when they attended the clinic. Regarding clinic appointment, 87% found the waiting area pleasant, 87% felt the clinic appointment met their expectations, 80% had an opportunity to voice their own opinion, 50% felt all their questions were answered with 33% stating most questions were answered. 50% were provided with written information and found it useful. 17% would like to have been seen without their parents. 27% had phoned the epilepsy nurse. Regarding appointment number, 70% feel they have the right number, 20% too few, 7% too many. Regarding time spent in clinic, 83% think it was enough, 10% too little. Conclusion: The response rate was low highlighting the difficulty engaging with teenagers. Respondents indicate a high level of satisfaction with the service, but there is room for improvement including provision of better information about the service and improving the environment.
p244 CAN A NURSE INTERVENTION PROMOTE THE SELFMANAGEMENT OF PATIENTS WHO ATTEND EMERGENCY DEPARTMENTS WITH ESTABLISHED EPILEPSY? A NESTED QUALITATIVE STUDY A. J. Noble*, C. Virdi, M. Morgan, and L. Ridsdale *Institute of Psychiatry, King's College London, 8AF, UK; Department of Clinical Neuroscience, London, UK; and King's College London, London, UK
Purpose: People with epilepsy (PWE) frequently attend emergency departments (EDs). Attendance is associated with AED non-adherence, low knowledge of epilepsy and stigma. Reducing unnecessary emergency hospitalisations could help patients and reduce costs. We are conducting a trial aimed to reduce epilepsy ED visits, by a self-management intervention with an epilepsy nurse-specialist (ENS). We here describe patients perceptions of acceptability and benefits. Method: N = 85 adults with epilepsy were prospectively recruited from 3 London EDs. The first 20 (age=41, SD=17; 10 males; median years since diagnosis=12) receiving the intervention were invited for semistructured interview. Transcripts were analysed thematically. Result: Participants reported not having been previously confident in managing their epilepsy, but that the intervention improved this. It did this by meeting a need for information on epilepsy, with the ENS being available in a way GPs and consultants are not: Responses included: It was the first time someone had sat down and really told me a huge amount; she took the time to go through my needs, you felt you could ask questions, not that wasting her time. Patients felt not so frightened of seizures. One said I don't feel as if I now need to go to hospital every time. Learning about epilepsy prevalence helped patients not feel so alone and less ashamed. They also felt AED adherence improved. Conclusion: This short intervention was acceptable to PWE who attended ED. It satisfied a perceived need for information and in turn increased confidence. We will report whether the intervention leads to reduced ED use subsequently.

p243 LEARNING ENVIRONMENT AT A PAEDIATRIC WARD A QUALITATIVE STUDY T. Lvenskjold Danish Epilepsy Center, Dianalund, Denmark
Purpose: At the paediatric department at Danish Epilepsy Center patient education given to children and parents is an important part of
73 Abstracts
p245 FACILITY OF EPILEPSY SERVICE IN THAILAND S. Towanabut*, S. Tiamkao, and S. Pranboon *Prasat Neurological Institute, Bangkok, Thailand; and Integrated Epilepsy Research Group, Khon Kaen University, Khon Kaen, Thailand
Purpose: This study was aimed at investigating the readiness of epilepsy services in Thailand. Method: The data was collected through questionnaires sent out to 1,033 public hospitals all over the country on their readiness in providing services to epileptic patients. 559 hospitals returned the questionnaires (54.11%). The data was then analyzed in percentages. Result: The results show that most epileptic doctors are general practitioners (30.4%). Epileptic specialists and neurologists account only for 11.1 and 14.4%, respectively. There are altogether 52 EEGs, 54 CT Scanners, and 6 MRIs. Four main types of antiepileptic drugs are prescribed to patients, namely, Phenobarbital, Phenytoin, Carbamazepine, and Valproic acid, at 99.9, 96.0, 97.9, and 89%, respectively. New antiepileptic drugs include Gabapentin, Topiramate, Levetiracetam, Lamotrigine, and Pregabalin (77.6, 63.9, 46.0, 45.3, and 33.6%, respectively). Vigabatin and Oxcarbazepine accounted for only 14.5 and 14.3%. Intravenous anticonvulsants used for status epilepticus patients include Phenytoin (54.2%), Gardinal sodium (33.9%), and Sodium valproate (12.1%). Only 45.7% of therapeutic drug monitoring can be done. Conclusion: There is still a limitation in the readiness of services in public hospitals. This is primarily due to a lack of doctors who specialize in treating epilepsy. Hospitals also lack diagnostic tools for antiepileptics and therapeutic drug monitoring. Therefore, a study needs to be conducted to develop a prototype model for epileptic treatment that is appropriate to the constraints and conditions of our country. Conclusion: The introduction of a strict protocol for pre-surgical patients leaving their room, usage of cot sides and a higher staff to patient ratio with increased training has made this Epilepsy Monitoring Unit more productive with a safer environment for those undergoing pre-surgical assessment. This study emphasises the benefit of staff training and telemetry protocols.
p247 NATIONAL AUDIT OF SEIZURE MANAGEMENT IN HOSPITALS: INITIAL FINDINGS A. G. Marson*, P. Dixon*, M. Pearson, J. Kirkham*, and K. Billington* *University of Liverpool, Liverpool, UK; and University Hospital Aintree, Liverpool
Purpose: Little is known about the organisation and delivery of epilepsy care in the UK. The National Audit of Seizure management in Hospitals (NASH) is the first comprehensive UK-wide epilepsy audit. Method: NASH assessed the immediate care, onward care pathways and prior care of patients attending Emergency Departments with seizures. Sites provided anonymous data on 30 consecutive cases via a bespoke web-based database. Result: Data were collected from over 3750 patients across 127 sites in the UK (mean age = 45.8 (SD 19.9), 57% male). 67% of the patients had established epilepsy whilst 18% presented as a result of their first seizure. Results show considerable variability, with a few sites performing well demonstrating that good care is possible. But overall, assessment on arrival was inadequate, routine measurements were not done (temperature in only 83% of patients), a proper neurological examination with plantar responses recorded in 37% (IQR 20.0 49.1), an attempt to gain an eyewitness description in 58% (IQR 43.3 73.3), and an ECG performed in 59% (IQR 43.3 75.8). It was not routine in most hospitals to ask patients who have had a seizure about driving despite the obvious road safety implications for themselves and others. Only 51% of first seizure patients were referred for any form of neurology specialist assessment. Conclusion: Basic care currently provided shows wide variability and in many centres is inadequate to achieve good patient outcomes. Neurologists and epileptologists have to engage with acute services to improve this. I can confirm that none of the authors for the abstract I submitted have conflicts of interest.
p246 IMPACT OF STAFFING LEVELS AND TRAINING ON PATIENT SAFETY & MANAGEMENT ON THE EPILEPSY MONITORING UNIT C. A. Mclaughlin*, M. C. Walker, B. Diehl, C. Scott*, T. Wehner*, and C. Milabo* *The National Hospital for Neurology and Neurosurgery, London, UK; Department of Clinical and Experimental Epilepsy, London, UK; and UCL Institute of Neurology, London, UK
Purpose: This audit aimed to assess the impact of changes to staffing levels, protocols and training on ictal and postictal management and interview in the Epilepsy monitoring Unit. Method: We carried out a retrospective analysis reviewing Video-EEG data and reports from Jan-Feb 2011 and compared findings to an earlier study. Since 2002 core nursing staff had been increased by 50%, a ward sister added and bed capacity increased. Speed of seizure attendance, care given, proportion of unrecognised seizures and seizure type were considered. Up to 5 seizures per extracranial pre-surgical patient were included. Seizures with subjective symptoms & no clear clinical change were excluded, giving a total of 90 seizures in 30 patients. Result: Significantly more seizures were attended in 2011 than 2002 (77% versus 59%, P < 0.05 Chi Square). There was also a non-significant tendency for a faster response time: median 28 s (range 0240s) in 2011 c/w 41s (range 0600s) in 2002 (P = 0.2 for difference, MannWhitney U test). Cot sides were more likely to be up during all seizures (81% in 2011 c/w 35% in 2002, P < 0.001) and this was particularly evident in tonic-clonic seizures (15/16 in 2011 versus 0/4 2002, P = 0.001 Fisher's Exact).
p248 AMBUFLEX/EPILEPSY IMPLEMENTATION OF PATIENT-REPORTED OUTCOMES IN EPILEPSY CLINICS L. M. V. Schougaard*, P. Sidenius, J. Christensen, L. Overbeck, B. J. Hanner, and N. H. Hjollund *Regional Hospital West Jutland, Herning, Denmark; and Aarhus University Hospital, Aarhus C, Denmark
Purpose: Patient-reported outcomes (PRO) are commonly used in clinical trials and observational studies. However, use of PRO in clinical practice is rare but may have several advantages. AmbuFlex is a web-based questionnaire system that implements PRO in the clinical decision making. Implementation of AmbuFlex for epilepsy involves several issues including disease related questions, setting and frequency of assessment, presentation of results and evaluation of the effect on the organization of patient care. Purpose: To implement AmbuFlex in 3 epilepsy outpatient clinics in Jutland, Denmark and thereby provide the patients with a more flexible care, improve; quality of treatment, patient self-management and utilization of resources in the health care system.
74 Abstracts
Method: The target group was all patients with epilepsy (n G 6500) associated with the 3 outpatient clinics. Three clinical expert groups were involved in the development of the epilepsy-questionnaire, which was tested on 20 epilepsy outpatients. Patients could choose to respond in either web or paper form. The results of the questionnaire were presented graphically for the clinicians within the individual, electronic medical records. Result: The pilot study provided useful information and apart from some problems due to recall bias and linguistic skills, most outpatients found the questionnaire easy to use. Patient referral to AmbuFlex is ongoing and the aim is to include the majority of patients associated with the 3 outpatient clinics. Conclusion: The results suggest that AmbuFlex is a flexible assessment program that may improve care for persons with epilepsy and optimize the use of resources in the health care system.
*HSE Dr Steevens Hospital, 8, Ireland; Change Management Training, 8, Ireland; HSE, 8, Ireland; and RCPI, 2, Ireland
Purpose: There is considerable variation in the provision and delivery of epilepsy care worldwide. Variation is at the root of disparities in quality, safety, access and value. In aviation, standard operating procedures (SOPs) are the distilled wisdom of professionals plus scientific evidence and have been developed over the last 3 decades, resulting in unparalleled quality and safety achievements. Healthcare is more complex than other industries but the use of SOPs, particularly by medical staff is rare. Method: In July 2011 the NECP in Ireland began a process of SOP development. Key clinical staff, patients and carers were invited to a professionally mediated workshop to determine key elements of excellence in epilepsy care covering ambulatory and acute care, diagnostics, therapeutics and prolonged Video-EEG monitoring units. Over the next 6 months, smaller groups met for 45 sessions to develop the SOPs. Result: 45 SOPs were developed which were put in a standardized Health Services Executive format. Twelve priority SOPs covering the three most important initial processes under each heading were endorsed by the clinical advisory group in Dec 2011 . All draft SOPs were posted in draft form on line in the spring on 2012 ready for small Plan, Do, Study, Act trials. Conclusion: The increasing complexity of modern healthcare demands that standardized procedures to reduce variation are required which will lead to improvements in quality, safety and cost. The NECP has developed 45 draft SOPs for improving epilepsy care that can act as templates for other national services.
p249 EPILEPSY CARE BY RAIL IN RURAL INDIA THINKING OUT OF THE BOX! M. B. Singh, R. Bhatia, M. Padma, M. Tripathi, and K. Prasad All India Institute of Medical Sciences, New Delhi, India
Purpose: To explore the possibility of a mobile clinic on the Lifeline Express using India's vast railroad network for spreading epilepsy awareness and conducting epilepsy screening clinics in remote, underserved parts of rural India. Method: The Lifeline Express arrives and stays at a new destination every month. We have organized a 23 day epilepsy clinic at each of its stops over the last 2.5 years. The epilepsy clinic screens patients who come in response to an extensive door-to-door campaign urging them to avail free services. Patients are interviewed, examined clinically, given a prescription and advised to follow-up and continue regular treatment. Epilepsy awareness activities amongst school children and teachers, and villagers are also carried out at each stop. Result: At Morena in the Central Indian state of Bihar, 144 patients (96 male) were examined on the LLE. The mean age was 24.7 years. A family history of epilepsy was present in 22.9% of the patients and a neurological deficit in 11.8%. A seizure frequency of at least 1/day, 1/week, 1/ month, 1/year or rarer was present in 15.7, 10.4, 58.3, 10.4 and 5.2 percent of patients respectively. Only 20.8% of the patients had ever been investigated with CT/MRI and 17.4% with an EEG. Patients who had never been treated with any AED were 37.5% Conclusion: Epilepsy treatment gap of >90% is reported from many parts of rural India. Innovative means of delivering epilepsy services combined with an emphasis on increasing epilepsy awareness are needed urgently. The Indian railways with its wide rural reach holds promise.
p251 LATE-LIFE REMISSION IN INTRACTABLE EPILEPSY: BURNT OUT EPILEPSY OR NATURAL HISTORY? M. Belluzzo*, J. Novy, G. Bell, M. Koepp, S. M. Sisodiya, and J. W. Sander *University of Trieste, Cattinara Hospital, Trieste, Italy; and UCL Institute of Neurology, London, UK
Purpose: Terminal seizure freedom in people with epilepsy is commonly considered an unlikely event if this is not reached in the early stages of the condition. In a subset of elderly people with long-standing refractory epilepsy, we aimed to see whether spontaneous remission can occur despite a life-long history of continuous seizures. Method: We carried out a retrospective evaluation of seizures patterns amongst people with longstanding pharmacoresistant epilepsy, institutionalized at the Epilepsy Society Chalfont Centre and who died between 1988 and 2009. Result: Among 122 people who had epilepsy for longer than 10 years, 26 (21%) reached a late, sustained remission (more than two years of seizure freedom). Seizure remission occurred at median age of 71 years and the median duration of seizure freedom was 6 years. Onset of remission was unrelated to medication changes in the vast majority of cases (92%). People who had experienced a previous interval of remission were more likely to be in remission at the time of death (p = 0.004, chi2). The length of the terminal remission was similar to that of previous remissions (p = 0.128, t test), but end of life remissions were more frequently spontaneous (p = 0.0016, Fisher exact test). Multivariate analysis suggests that older age at death was the only variable directly linked to the likelihood of late remission. Conclusion: Our study provides some preliminary evidence that for some people with epilepsy there is a natural tendency for seizures to stop with advancing age.
p250 THE DEVELOPMENT OF STANDARD OPERATING PROCEDURES (SOPS) IN EPILEPSY CARE TO REDUCE VARIABILITY AND TRANSFORM A NATIONAL SERVICE. NATIONAL EPILEPSY CARE PROGRAMME, (NECP) DIRECTORATE OF CLINICAL STRATEGY AND PROGRAMMES, HEALTH SERVICE EXECUTIVE, DR. STEEVENS HOSPITAL, DUBLIN, IRELAND. ROYAL COLLEGE OF PHYSICIANS, DUBLIN, IRELAND. CHANGE MANAGEMENT TRAINING M. E. White*, M. Harris, M. White, S. Morrow, and C. Doherty*
75 Abstracts
p252 COMPARATION OF PROGNOSIS BETWEEN PATIENTS WITH AND WITHOUT EPILEPTIC SEIZURES AS A FIRST MANIFESTATION OF STROKE S. Z. Atic Hospital for Cerebrovascular Diseases Sveti Sava, Belgrade, Serbia
Purpose: Epileptic seizure is very often present as a first manifestation of stroke. The aim of our study was to compare the prognosis between patients with and without epileptic seizures as a first manifestation of stroke. Method: We studied patients with acute stroke admitted to our hospital during the same period, using a standard protocol including at least one MR/CT scan, electroencephalography (EEG) and neurological examinations. The patients were divided into the two groups:1. study group with epileptic seizures as a first manifestation of acute stroke 2. control group with acute stroke and without epileptic seizures. All of those patients were analyzed within 3,6,9 and 12 months of stroke. Result: 104 patients with acute stroke were attended,46 female and 58 male, age range 39 to 83.48 were observed in the study group and 56 in the control group. After 3 months 5/48 patients from the study group and 3/56 from the control group had died. After 6 and 9 months 40 patients(15 from the study and 25 from the control group) were not available, but 12 from the study group and 5 from the control group had died. After 12 months of follow-up 15 patients were hospitalized again.10 of those have had a repetitive or the first epileptic seizures but without acute stroke. Conclusion: We did not find significant differences in prognosis between all patients after 3 and 6 months, but increased mortality after 9 and 12 months of follow-up. The frequncies of repetitive seizures and mortality were higher between patients with previous seizures, but also depend of type of stroke. Result: At two years, in the surgical group there was 19/26 patients seizure free (73%), 4 patients (15%) had a seizure frequency lower than a seizure per month, and only a patient (4%) had more than one seizure per month. At five years 15 patients remained for analysis: 11 were seizure free (73,3%), and 4 (26,7%) had less than a monthly seizure. 7 patients had postoperative neurological sequelae. In the medical treatment group, 12/17 patients were seizure free (70.6%), without significant differences (p = 0.2 and 0.3 respectively). Conclusion: In patients with non-refractory epilepsy surgical approach of cavernomas did not raised a significative better control of seizures than medical treatment, and surgery has potential serious risks. As these results are not definitive, it is still necessary a prospective and randomized study to resolve this uncertainty.
p254 ANTIEPILEPTIC DRUG SUSPENSION IN ADULT PATIENTS-ASSESSMENT OF RISK FACTORS S. M. Vujisic, D. B. Milikic, L. B. Radulovic, and S. Vodopic Clinical Centre of Montenegro, Podgorica, Montenegro
Purpose: To deremine risk factors for the appearence of relapse attacks after antiepileptic drugs suspension. Method: A group of patients who had the AE treatment stopped, by advise and agreement with the doctor, or on the basis of self-initiative were examined. The study only included patients who had repeated epileptic attacks. All the patients had detailed questionnaire filled up, and all of them had neurological examination, EEG and MRI done. Etiology was classified into simptomatic, idiopatic and kriptogenic. Result: A group of 43 patients (aged from 16 to 75 years) were examined due to epileptic attacks after exlusion of the AE therapy. There were 20 male and 23 female patients. Most of the patients were 16 to 35 years old, i.e 34 (79%). Eighteen patients had idiopatic (42%), thirteen patients had kriptogenic (30%), and twelve had symptomatic epilepsy (28%). Our study has shown that significantly large number of patients (p Conclusion: The most relapses of epileptic attacks occur in the first two years after discontinuation of AE therapy. Risk factor for recurrence is patological EEG. Our study has shown that there was no significant diferences in the occurance of relapse regarding etiology.

p253 SURGICAL VERSUS CONSERVATIVE TREATMENT IN PATIENTS WITH CEREBRAL CAVERNOMAS AND NON REFRACTORY EPILEPSY S. Fernndez*, J. Mir, M. Falip, G. Plans, S. Castanyer, A. Fernndez-Coello, and J. J. Acebes *Hospital Plat, Barcelona, Spain; and Hospital Universitari de Bellvitge, LHospitalet de Llobregat, Spain
Purpose: Patients with cerebral cavernomas often presents with seizures. It is still unclear if surgery is the optimal approximation in patients with cavernomas and new onset epilepsy, sporadic seizures or non well established refractory epilepsy. The aim of this study was to compare the seizure frequency of patients with cerebral cavernomas operated and non operated, in order to obtain more information to the correct management of these patients. Method: We studied retrospectively 43 patients with non refractory epilepsy secondary to cerebral cavernoma. 26 patients (60.5%) underwent surgery and made up the surgical group, and 17 patients were treated medically and constituted the medical group. Seizure frequency, need of antiepileptic drugs post-treatment and other clinical variables were compared between both groups.
p255 PROVOKED SEIZURES AND FUNCTIONAL OUTCOME ONE YEAR AFTER ACUTE ISCHAEMIC STROKE H. Sentes-Madrid*, E. Chiquete*, C. Cant-Brito*, J. L. RuizSandoval, M. Alonso-Vanegas, and G. Garca-Ramos* *Instituto Nacional de Ciencias Mdicas y Nutricin Salvador Zubirn, Mexico City, Mexico; Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara, Mexico; and Instituto Nacional de Neurologa y Neurociruga MVS, Mexico City, Mexico
Purpose: To describe the factors associated with provoked seizures after acute ischaemic stroke and the impact on functional outcome at one year of follow up. Method: This is a descriptive cohort study on 1246 non-epileptic patients with acute ischaemic stroke included in a multicentre Mexican registry, who received long-term follow up after a first-ever or recurrent brain infarction. Multivariate analyses were performed to evaluate factors associated with provoked seizures and the functional outcome at 12 months of follow up.
76 Abstracts
Result: The frequency of provoked seizures after acute ischaemic stroke was 8.1% [95% confidence interval (CI): 6.7% to 9.8%]. In a binary logistic regression model, risk factors significantly associated with provoked seizures were a scoring of the National Institutes of Health Stroke Scale (NIHSSS, US) >10 [odds ratio (OR): 2.21, 95% CI: 1.403.47], recurrent ischaemic stroke (OR: 2.17, 95% CI: 1.34 3.53) and age 3) at 12 months of follow up [hazard ratio (HR): 1.37, 95% CI: 1.041.83], as well as NIHSS >10 (HR: 4.47, 95% CI: 3.53 5.65), age 65 years (HR: 1.74, 95% CI: 1.382.20), heart failure (HR: 1.61, 95% CI: 1.222.13) and atrial fibrillation (HR: 1.35, 95% CI: 1.051.74). Conclusion: The frequency of provoked seizures after acute ischaemic stroke in this cohort was 8%. Age. of epilepsy in patients suffering CVT. Our objective was to analyse the risk factors for epilepsy after CVT, in a long-term follow-up. Method: This is a cohort study on consecutive non-selected patients with acute cerebrovascular disease, systematically registered from 1986 to 2010 in two referral centres of Mexico City. Here we analysed 340 patients who survived the first 6 months after CVT, who were not epileptic at baseline and for whom complete long-term information on neurological outcome was available. Result: Seizures occurred in 183 (54%) patients, in 26% of them as a clinical presentation and 74% at some point during the follow-up. Focal motor seizures occurred in 6.5%, secondary generalised focal seizures in 13.8%, and generalised tonic-clonic seizures in 22.4%. Status epilepticus occurred in 13 (7%) cases. In all, during a median follow-up of 28 months (range 2 to 288 months), epilepsy was present in 14.7% (27.3% of those who presented seizures). In a multivariate analysis adjusted for multiple confounders, risk factors associated with an increased risk of epilepsy during follow-up were having seizures as the clinical presentation of CVT [odds ratio (OR): 4.32, 95% confidence interval (CI): 2.208.48], pregnancy and puerperium (OR: 2.03, 95% CI: 1.113.71) and thrombosis of the longitudinal sinus (OR: 1.86, 95% CI: 1.013.41). Conclusion: Seizures are common at CVT presentation, but the risk increases during the following days after the thrombotic event. Most seizures resolve during the first month, but epilepsy occurred in 15% of patients with CVT in the long run.
p256 EPILEPSY REMISSION STAGE STATEMENT BY NONLINEAR METHODS FOR EEG RESULTS PROCESSING S. Artsiomenka*, V. Kistsen*, V. Golovko, and V. Evstigneev* *Belarussian Medical Academy of Postgraduate Education, Minsk, Belarus; and Brest State Technical University, Brest, Belarus
Purpose: Epilepsy remission stage statement and well-founded AEP dose lowering decision are the key points in epilepsy patients treatment. We created and used the automatic diagnostic system (ADS) for EEG paroxysmal activity detection to estimate epilepsy remission stage and to early exacerbation prognosis. Method: We applied the Neural-Net Method to make the assistant diagnostic system and examined this system on real EEG data. The largest Lyapunov's exponent is used as a criterion for the paroxysmal activity detection. Therefore a value of the largest Lyapunov's exponent was positive for chaotic behavior of a system and decrease when the epilepsy activities occur. There were observed 36 patients in epilepsy clinical remission stage by EEG every 3 month during 13 years and then estimated results by our ADS. ADS detect parts of EEG which are not chaotic unlike normal electrical brain activity and gives 2dimension map with colored abnormal parts red. Result: ADS display paroxysmal activity when usual analysis EEG not detects anomalies. ADS showed periodically anomaly activity various duration in background and particularly photostimulation EEG of all patients with tendency to disappearance of it during correct therapy (p < 0.05). ADS revealed a growth presence of hidden paroxysmal activity near 612 months before exacerbation of disease. Conclusion: Automatic diagnostic system for EEG paroxysmal activity detection can use to estimate epilepsy remission or exacerbation stage with prognosis of pre-seizure changes in the EEG signal dynamic to predict a seizure occurrence and to correct the AEP doses.
p258 LONG-TERM OUTCOME AFTER COGNITIVE AND BEHAVIORAL REGRESSION IN NON-LESIONAL EPILEPSY WITH CSWS E. Roulet Perez*, T. Deonna*, C. Mayor-Dubois*, M. P. ValentiHirsch, E. Hirsch, M. Metz-Lutz, A. De Saint-Martin, and C. Seegmller *Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; and University regional hospital centre of Strasbourg, Strasbourg, France
Purpose: To present the long-term outcome (LTO) of 10 adolescents and young adults with documented cognitive and behavioral regression as children due to non-lesional focal, mainly frontal epilepsy with continuous spike-waves during slow wave sleep (CSWS). Method: Past medical and EEG data of all patients were reviewed and neuropsychological tests exploring main cognitive functions were administered. Result: After a mean duration of follow-up of 15.6 years (range 823 years), none of the 10 patients had recovered fully, but four regained borderline to normal intelligence and were almost independent. Patients with prolonged global intellectual regression had the worst outcome, whereas those with more specific and short-lived deficits recovered best. The marked behavioral disorders that were so disturbing during the active period (AP) resolved in all but one patient. Executive functions were neither severely nor homogenously affected. Three patients with a frontal syndrome during the AP disclosed only mild residual executive and social cognition deficits. The main cognitive gains occurred shortly after the AP, but qualitative improvements continued to occur. LTO correlated best with duration of CSWS. Conclusion: Our findings emphasize that cognitive recovery after cessation of CSWS depends on the severity and duration of the initial regression. None of our patients had major executive and social cognition deficits with preserved intelligence as reported in adults with destructive lesions of the frontal lobes during childhood. Early recognition of epilepsy with CSWS and rapid introduction of effective therapy are crucial for a best possible outcome.
p257 EPILEPSY AS A CHRONIC COMPLICATION IN CEREBRAL VENOUS THROMBOSIS: A 20YEAR FOLLOWUP E. Chiquete*, C. Cant-Brito*, M. Merloz-Benitez, A. Arauz, H. Sentes-Madrid*, and M. Alonso-Vanegas *Instituto Nacional de Ciencias Mdicas y Nutricin Salvador Zubirn, Mexico City, Mexico; and Instituto Nacional de Neurologa y Neurociruga MVS, Mexico City, Mexico
Purpose: Seizures represent a common clinical presentation of cerebral venous thrombosis (CVT); however, little is known about the future risk
77 Abstracts
p259 TEN-YEAR MORTALITY AMONG PEOPLE WITH EPILEPSY (PWE) AT A PRIMARY HEALTH CARE LEVEL: THE CASE OF THE MBAM AREA OF CAMEROON J. Y. Fonsah*, R. Nchufor, R. Nditanchou*, Y. F. Fogang*, A. Acho*, R. F. Doh*, F. Dema*, E. N. Tabah, V. Sini*, A. C. Z. Bissek*, W. F. Muna, and A. K. Njamnshi *Central Hospital Yaounde, Yaounde, Cameroon; Sub Divisional Hospital Ndu, Yaounde, Cameroon; and Neurology Department, Central Hospital Yaounde, Cameroon; FMBS UYI Cameroon, Yaounde, Cameroon
Purpose: We aimed at contributing to the improvement of epilepsy care in PWE, understand the natural history of epilepsy, determine the mortality and its principal causes in a group of PWE in the Mbam area of Cameroon. Method: A retrospective analysis of all case files diagnosed with epilepsy from 1999 to 2000 in the Mbam area was done. A total of 820 files of patients followed up in an existing, community-dependent, nurse-controlled and neurologist-supervised missionary epilepsy programme were studied amongst which 192 were analysed. Result: A mortality rate of 15.1% was obtained with a SMR of 8.9. More deaths were recorded amongst females (65.5%) and people of the age group 1625 years (73.2%). Most people lived with the epileptic condition for 1115 years (42%) before dying with a mean duration of illness of 11.65 years. Bilomo and Badissa alone recorded more than 50% of all deaths. The main causes of death were status epilepticus (42.3%), drowning (23.1%) and sudden unexplained death (7.7%). Conclusion: The mortality amongst PWE is high in the Mbam area and involves more females and youths. Status epilepticus and drowning are common causes of death.
p261 PROGNOSTIC FACTORS FOR TIME TO TREATMENT FAILURE AND TIME TO 12 MONTH REMISSION FOR PATIENTS WITH GENERALISED EPILEPSY: POST HOC AND SUBGROUP ANALYSES OF SANAD L. J. Bonnett*, C. Tudur Smith*, D. Smith, P. Williamson*, D. Chadwick, and A. Marson *University of Liverpool, Liverpool, UK; and Walton Centre for Neurology and Neurosurgery NHS Foundation Trust, Liverpool, UK
Purpose: Epilepsy is a heterogeneous condition with outcomes ranging from immediate remission on a first antiepileptic drug through to frequent unremitting seizures with multiple treatment failures. There are currently few published prognostic models for epilepsy that allow informed decision making based on predicting outcomes overall and on specific treatments. Method: A list of potential prognostic factors was established and univariate and multivariable analyses using Cox regression models were undertaken. Variables were centred to diminish multicollinearity and continuous variables were investigated by log or fractional polynomial transformations. Parsimonious multivariable models were produced with variable reduction by Akaike's Information Criterion. Result: Multivariable models identified a number of significant factors. For time to treatment failure, treatment history (recent seizures following previous remission vs treatment naive: HR 2.01 95% CI (1.18 to 3.41)), EEG results (no results vs normal results: HR 2.45 95% CI (1.46 to 4.09)), total number of seizures before randomisation (e.g. 48 vs 2: HR 1.49 95% CI (1.19 to 1.85)) and treatment (topiramate vs valproate: HR 1.62 95% CI (1.22 to 2.16)) were significant factors. For time to 12 month remission significant factors were relatives with epilepsy (present vs absent: HR 0.75 95% CI (0.59 to 0.95)), neurological insult (present vs absent: HR 0.70 95% CI (0.52 to 0.93)) and total number of seizures before randomisation (e.g. 48 vs 2: HR 0.41 95% CI (0.33 to 0.51)). Conclusion: Subject to external validation, this prognostic model should aid individual patient risk stratification and the design and analysis of future epilepsy trials.
p260 LONG-TERM OUTCOME IN ABSENCE EPILEPSIES M. Holtkamp, D. Janz, and A. Kirschbaum Epilepsie-Zentrum Berlin-Brandenburg, Berlin, Germany
Purpose: Absence epilepsies are classified regarding age at onset into childhood (10th year of life) and juvenile (>10th year) and regarding clinical course with high- and low-frequency seizures into pyknoleptic and non-pyknoleptic forms. Prognostic data may help to clarify if these represent different entities or constitute parts of a clinical continuum that is based on the same neurobiological syndrome. Method: 147 patients with absence epilepsies and a follow-up of 20 a were included. Diagnostic allocations were made on the basis of clinical and EEG data derived from patient charts. Terminal remission was defined as seizure freedom in the last 5 years. Result: After a mean follow-up of 45 15 years, 75 patients (51%) were seizure free, 22 of those were tapered off antiepileptic drugs (AED). Following multivariate analysis, history of generalised tonic-clonic seizures (GTCS) (OR 7,680; CI95% 1.54638.159; p = 0.013) and age at investigation (OR 0.958; CI95% 0.9350.982; p = 0.001) were independent predictors for lacking remission. Conclusion: More than half of the patients with absence epilepsies were seizure free for the last 5 years, one third of those did not take AEDs. Thus, nearly one in six patients was cured from absence epilepsy almost half a century after onset. Lack of remission was a function of patients age and occurrence of GTCS. Neither age at epilepsy onset nor the clinical course with pyknoleptic vs. non-pyknoleptic absences was associated with long-term outcome. This important clinical feature biologically rather argues for a continuum than for a dichotomisation of absence epilepsies into a childhood and juvenile form.
p262 MORTALITY AND SUDEP IN EPILEPSY PATIENTS TREATED WITH VAGUS NERVE STIMULATION C. A. Granbichler*, L. Nashef, C. E. Polkey, and R. Selway *Christian Doppler Klinik, Salzburg, AustriaKing's College Hospital, London, UK; and Kings College London, London, UK
Purpose: Data on mortality with Vagus Nerve Stimulation (VNS) for epilepsy are limited. In one study, standardized mortality ratio (SMR) was 5.3 [95% confidence interval (CI) 3.08.7] with a rate of definite/ probable SUDEP of 4.5/1,000 person-years (py) (Epilepsia 1998 Feb;39(2):20612). Mortality rates were lower (SMR = 3.6) with extended follow-up. Stratified by duration of use, SUDEP rate was 5.5/ 1,000 over the first 2 years, and 1.7 per 1,000 thereafter (Epilepsia 2000 May;41(5):54953). To establish mortality rates, identify epilepsyrelated deaths and calculate SUDEP rates in patients treated with VNS for epilepsy. Method: All UK-based patients undergoing VNS at King's College Hospital, London, between 1st January, 1995 and 31st December, 2010 were included. Deaths were ascertained from the national death register. Information on cause and circumstances of death were obtained as appropriate. Deaths were designated as epilepsy or not epilepsy related and SUDEP cases classified using the unified definition (Epilepsia, 53(2):227233, 2012). SMRs were calculated on an intention to treat basis.
78 Abstracts
Result: There were 445 patients (2734 person-years [py], median follow-up 6.1 years) and 29 deaths (SMR 7.6 [95% Confidence Intervals (CI), 5.310.9]. On preliminary classification, 13 deaths were epilepsyrelated, including 7 SUDEP (5 definite, 2 probable), and 3 are unclassified (further information awaited). Overall SUDEP rate/1000 py was 2.6, 2.4 during the first two years, and 2.7 thereafter. Conclusion: SMR in our cohort is higher but not significantly so. Preliminary results do not confirm a decrease in SUDEP rate beyond the first two years in this cohort. DEP). The exact mechanisms of SUDEP are not known and several hypotheses (such as cardiac, respiratory, autonomic causes) have been advanced. People with epilepsy also seem to have more concomitant medical conditions than the general population; some cardiac co-morbidities (such as Brugada syndrome) may play a role. We aim to explore the prevalence of significant cardiac arrhythmias in these people. Method: To date, we have collected consecutive standard (12 leads) ECGs of 100 people assessed for chronic epilepsy in 2010 in a tertiary referral centre. ECGs were reviewed by an experienced cardiologist (HLT), looking for subtle abnormalities. All concomitant medications as well as cardiovascular risk factors and history were taken into account. Result: In those 100 people, amongst other abnormalities detected, the ECGs of two were highly suggestive of Brugada syndrome. Neither was previously known to have this condition and this had not been detected by automated analysis of the ECGs or by previous review. Conclusion: The prevalence of Brugada syndrome may be higher in people with chronic epilepsy than in the general population where it was found in several studies to be less than 0.1%. This condition is known to be lethal and could be responsible for some cases of SUDEP. Channelopathies affecting both heart and brain could explain its increased occurrence in epilepsy. We aim to increase the size of our sample to confirm these findings.

p263 IS TERMINAL REMISSION WITHOUT THERAPY POSSIBLE IN PATIENTS WITH JUVENILE MYOCLONIC EPILEPSY? N. J. Jovic, and A. Kosac Clinic of Neurology and Psychiatry for Children and Youth, Belgrade, Serbia
Purpose: It has been generally accepted that juvenile myoclonic epilepsy (JME) is lifelong and that it is unwise to discontinue treatment once seizure control has been established. The evolution of JME in patients with long-term seizure freedom and antiepileptic drugs (AEDs) discontinuation was assessed. Method: We retrospectively analyzed clinical course of 87 JME patients (38 male, 49 female) aged from 17.5 to 43.5 years (mean 27.6), with mean seizure onset of 14.6 years (range 8.320.8). Result: Complete seizure control was achieved in 67 (77.0%) patients mainly with valproate (55 patients). Pseudo-resistant seizures occurred in 9.2%, while JME was refractory in 13.8% patients. Therapy was discontinued in 34 (39.1%) patients (in 13 by their own choice after 5.3 + 2.4 and in 21 following advice of a physician after 8.5 + 5.2 years of seizure freedom). In 18 subjects seizures relapsed after mean 1.1 year (range 7 days to 4 years) and AED was restarted. In two patients the AED was reintroduced because of EEG aggravation. Seizure and drug freedom of mean 5.1 years (range 3.512 years) was noted in 11.5% patients. Nonintrusive myoclonic seizures recurred for 2.44 years as their only seizure type in 4 subjects, but without restarted medication. Conclusion: Terminal remission without AEDs is possible in JME patients. Non-compliant individuals have lower chance to achieve it. All seizure types in JME resolved in 11.5% and for 4.6%, only myoclonus persisted. Therefore, 16.1% of adolescents and young adults with JME have troublesome seizures vanished and AED treatment was no needed for years.
p265 HAS TREATMENT OF EPILEPSY IMPROVED IN THE PAST 10 YEARS? THE IMPACT OF EPILEPSY TREATMENT IN THE PAST 10 YEARS; A COMMUNITYBASED COMPARISON STUDY M. Wassenaar*, F. S. S. Leijten, P. Van Der Linden, S. G. Uijl, A. C. G. Egberts, and J. A. Carpay *UMC Utrecht, Utrecht, The Netherlands; Rudolf Magnus Institute of Neuroscience, UMC Utrecht, Utrecht, The Netherlands; Tergooi ziekenhuizen Blaricum, Blaricum, The Netherlands; Julius Center for Health Sciences and Primary Care, UMC Utrecht, Utrecht, The Netherlands; and Utrecht Institute for Pharmaceutical Sciences, University Utrecht, Utrecht, The Netherlands
Purpose: New-generation AEDs have increased the number of treatment options for epilepsy and are promoted because of better safety profiles. It is unknown if this has resulted in better patient outcomes in daily practice. We describe 10year changes in quality of life (QoL), seizure control and drug-related adverse effects (DRAEs) in a community-based sample of epilepsy patients and assesses potential predictors of QoL. Method: From two cross-sectional community-based studies performed in 2000 and 2010 in a Dutch suburban region, responses to standardized questionnaires on treatment outcomes were compared. Epilepsy patients were identified using pharmacy records, 344 and 247 patients were included respectively. Additionally, factors, among which seizure control and DRAEs, predicting QoL were assessed by multivariate linear regression. Result: New-generation AEDs prescription in 2010 increased to 44.5% from only 10.5% in 2000. Treatment outcomes did not differ between new and old-generation AEDs. In 2010 compared to 2000, QOLIE-31 scores did not differ (72.48 vs 72.54), neither did the proportion of patients reporting well-controlled seizures (55.1% vs 50,5%). However, seizure acceptability increased (54.3% vs 40.3%) and AEs were significantly more reported (82.0% vs 58.9%). Seizure control, DRAEs and seizure acceptability jointly predicted QoL score (R2 = 51%). Conclusion: The introduction of new AEDs has not improved QoL in the past decade. Whereas seizure acceptability increased, seizure control
p264 CARDIAC ARRHYTHMIAS MAY BE UNDERESTIMATED IN PEOPLE WITH CHRONIC EPILEPSY R. J. Lamberts*, J. Novy, H. L. Tan, R. D. Thijs*, and J. W. Sander *SEIN-Epilepsy Institute in the Netherlands Foundation, Heemstede, The Netherlands; UCL Institute of Neurology, London, UK; and University of Amsterdam, Amsterdam, The Netherlands
Purpose: People with chronic epilepsy are known to be at risk of premature mortality mainly due to sudden unexpected death in epilepsy (SUEpilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x
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remained similar and DRAEs were reported more frequently. Since all these factors contributed to QoL, reduction of DRAEs should be prioritized to improve QoL in epilepsy patients. Conclusion: Neurological status and EEG are crucial parameters which could identify infants at risk of CP and epilepsy.
p266 CARBAMAZEPINE AND OXCARBAZEPINE TRIGGERED EPILEPTIC NEGATIVE MYOCLONUS AGGRAVATION IN CHILDHOOD K. Y. Mukhin, and M. B. Mironov St. Luka's Institute of Child Neurology and Epilepsy, Moscow, Russia, Moscow, Russian Federation
Purpose: Investigation of patients with ENM induced by Carbamazepine (CBZ) and Oxcarbazepine(OXC). Method: The 12 patients with ENM who have been taking CBZ or OXC in the course of treatment. In 10 of 12 cases, ENM was induced by these drugs. Result: In 10 cases (83,3%) ENM aggravation was noted. As our results show, there are several CBZ/OXC triggered ENM aggravation risk factors: males prevail over females at a ratio of 4 to 1; age of onset of epilepsy: from 1 year to 13 years of age with a peak between the ages of 3 and 8 years; forms of epilepsy: FEBL-BEDC 5 cases, epileptic encephalopathies associated with BEDC 3 cases, symptomatic focal epilepsy with SBS on EEG 1 case, progressive myoclonus epilepsy (PME) 1 case. Types of seizures preceding the ENM events: hemiconvulsive 7 patients; SGTCS 5 cases; tonic seizures 2; occipital focal seizures 2; GTCS 1; myoclonic seizures 1 case.
p268 RELIABILITY AND VALIDITY OF A SPANISH VERSION OF THE IMPACT OF PEDIATRIC EPILEPSY SCALE IN A CUBAN POPULATION N. Garfalo Gmez, O. Fernndez Concepcin, and A. M. Gmez Garca Cuban Institute of Neurology and Neurosurgery, Havana, Cuba
Purpose: The Impact of Pediatric Epilepsy Scale (IPES) is a brief, accurate, and acceptable measurement scale of the impact of pediatric epilepsy on the Health Related Quality of Life (HRQOL) of both the child and family as perceived by the child's parent(s) and has been previously validated in Canadian and Chinese children with epilepsy. The aim of this study was to validate a Spanish language version the IPES in Cuban children with epilepsy. Method: The IPES was translated and adapted to Cuban culture and administered to 76 parents of children with epilepsy. Result: The principal component analysis indicated that two factors accounted for 72% of the variance of IPES scale (family relationships and health and social well-being). The IPES also was able to detect differences in health-related quality of life (HRQOL) between subjects according to epilepsy severity. Internal consistency coefficients were 0.962 and the test-retest reliability was 0.979. Conclusion: The Cuban Spanish version of IPES has good validity and reliability, and can be used to measure a child's epilepsy specific HRQOL in Cuba and probably in other Spanish speaking communities.
p267 NEONATAL PARAMETERS AS PROGNOSTIC FACTORS FOR EPILEPSY OR CEREBRAL PALSY IN INFANTS WITH HYPOXIC-ISCHEMIC ENCEPHALOPATHY N. M. Cerovac, and N. J. Jovic Department for Neurology and Psychiatry for Children and Youth, Medical School, Belgrade, Belgrade, Serbia
Purpose: The survivours with hypoxic-ischemic encephalopathy (HIE) were studied to evaluate the prognostic value of neonatal parameters as risk factors for cerebral palsy (CP) and epilepsy. Method: A group of 45 infants with HIE were retrospectively assesed at birth and at seven year of age. Perinatal conditions, neonatal parameters, neurological status, 5-minute Apgar score and early electroencephalogram (EEG) were analysed. Result: The neurological outcome at the age of seven years was normal in 9 infants (20%) and abnormal in 36 (80%). Both epilepsy and CP developed in 9 infants (20%), only motor delay in 30%, only epilepsy in 4% or only CP in 26%. Seizures were classified as infantile spasms (4 infants), complex focal (3) and generalized tonicclonic (2). Obstretic complications were:pre-eclampsia (13%), abruptio placentae (11,1%), chorioamnionitis (20%), breech delivery (11%), cord prolapse (11%), meconium (20%) and caesarean section (33%). The mean gestational age of the group was 36 weeks, mean birth weight 2,4 kg and the mean Apgar score 6,9. The neonatal neurological status was normal in 31% of infants and abnormal in 69%. Early EEG was normal in 22% of infants and abnormal in 78% (abnormalities in EEG background rhythm and/or pathologic patterns). The results of our study confirm that neonatal neurological status (v2 = 11,431; p = 0,0007) and early EEG (v2 = 8,481; p = 0,0036) were a good predictive factors in terms of neurological sequelae, while other neonatal parameters did not show such a good correlation.
p269 MANAGEMENT OF ACUTE SYMPTOMATIC SEIZURES OUTLINE OF CURRENT PRACTICE R. Powell, and I. M. Sawhney Morriston Hospital, Swansea, UK
Purpose: Acute symptomatic seizures (ASS) are seizures occurring at the time or in close temporal association with a documented systemic or brain insult. The major issues involved in their management are the diagnosis and treatment of the underlying cause, whether seizures should be treated or not, and the choice and duration of anti-epileptic drug (AED) treatment. These decisions are not straightforward and currently no clear guidelines exist to guide management in this area. Method: We reviewed the literature on risks of ASS and epilepsy following a number of common conditions. Result: We outline our current practice in this area which is based on the evidence available on risks of seizure recurrence, and on our own experience. Conclusion: Most ASS only need short term therapy (up to 3 months) if there is complete recovery from the acute insult. Patients with residual structural brain abnormalities with focal neurological deficit and/or MRI changes need long term prophylactic treatment. We make some suggestions for duration of treatment for ASS associated with a number of common conditions, including; subarachnoid and intracerebral haemorrhage 1 year ischaemic stroke and venous sinus thrombosis 1 year mild to moderate head injury acute seizure control only severe head injury 2 years -metabolic and toxic disorders (including alcohol withdrawal) correction of underlying cause only meningoencephalitis with complete recovery, normal MRI 3 months, residual focal deficit and/or MRI changes 2 years - cerebral abscess, tuberculoma and parasitic granuloma 2 years
80 Abstracts
p270 REFRACTORY SEIZURES AND QOL: CAN A PATIENT BE WORSE OFF ON AEDS? 3 CASE STUDIES S. White, and L. D. Mewasingh Imperial College Healthcare NHS Trust, London, UK
Purpose: 3 clinical cases are discussed whereby the common theme is that of refractory seizures, of different aetiologies, but nontheless raising the question of whether polypharmacy is justified when clinically there do not seem to be any significant clinical response to various AEDS in different combinations over time. In each case the seizures have been proven to be concordant with numerous electrographic recordings over a period of time. Method: Aetiologies: Case 1: a 2 year old with severe neonatal herpes encephalitis with significant sequelae (4limb cerebral palsy, cortical blindness, numerous seizure types as well as non-epileptic movement disorder) and feeding problems Case 2: a young boy with Wolf Hirshorn and refractory epilepsy disorder including episodes of nonconvulsive status epilepticus, resistant to various AEDs as well as no clincal response to ketogenic diet Case 3: a teenager with herpes simplex encephalitis acquired in her primary school years with frontal disinhibition, moderate learning difficulties and refractory seizure disorder. Result: In the first two cases parents were clear that they did not wish for further medications, perceived as of minimal benefit and resulting in decreased alertness. In the third case, parents and professionals differed in what was perceived as optimal QOL for the young person, with the former keen to pursue various therapeutic avenues with little clinical tangible improvement. Conclusion: The issues of QOL, polypharmacy, perceived side effects of treatment versus benefits are raised and discussed. This can at times lead to the dilemma of whether to treat and how aggressively to treat seizures in this context. Conclusion: Clinical record keeping was generally poor particularly regarding the circumstances surrounding deaths and raising awareness of SUDEP among patients/carers. There was also an absence of post-mortem reports and no record of support provision for families to cope with their bereavement in the majority of cases.
p272 EPILEPSY AND PSYCHIATRIC DISORDERS IN A LEARNING DISABILITY PATIENT'S SERIES V. C. Monetti, E. Fallica, V. Govoni, and E. Cesnik Azienda Ospedaliero Universitaria di Ferrara, Ferrara, Italy
Purpose: Epilepsy is most frequent in Learning Disability (LD) patients. The frequency ranges from 6% (moderate LD) to 50% (severe/profound LD). The object of our study is to analyse a LD outpatients series followed up in the Adult Epilepsy Center of Ferrara Hospital to evaluate their long-term prognosi and eventual conditioning clinic and psycosocial factors involved. Method: In the Ferrara Hospital Adult Epilepsy Center database LD patients, in follow-up from more than 10 years with the last examination in the years 20102011, were identified. Their data were crossed with the data of the same patients who were previously followed-up in the Paediatric Epilepsy Center to obtain a long-term observation. Result: 86 patients were identified (35 F, 51 M, mean age 41 years). 76% of them had a symptomatic Epilepsy (mainly pre- post-natal injury anda cerebral malformations) whereas 9% had a chromosomal-genetic disorder. In the 43% of the cases the seizures frequency was high (>2/ month) from the onset with no significant improvement over time. 48% of patients had a drug-resistant epilepsy. Psychiatric disorders were present in 48% of patients and almost all of them were institutionalised. Conclusion: Our findings support limited evidence from the literature that the LD severity does not affect the prognosis of epilepsy as the high frequency of seizures at onset. Psychiatric comorbidity is prognostically unfavourable factor for an institutionalization.
p271 A STUDY OF STANDARDISED MORTALITY RATE IN PEOPLE WITH INTELLECTUAL DISABILITY WHO DIED OF SUDDEN UNEXPECTED DEATH IN EPILEPSY (SUDEP) R. Kiani Leicestershire Partnership NHS Trust, Leicester, UK
Purpose: To calculate the mortality rate of Sudden Unexpected Death due to Epilepsy in people with intellectual disability and evaluate the quality of epilepsy management they received from an adult intellectual disability service. Method: All adults, with an intellectual disability, who had died because of epilepsy between 1993 and 2010 were identified using the Leicestershire Intellectual Disability Register database. Death certificates and post-mortem reports were used to ascertain the cause of death. Case notes review was then carried out to collect further information. Result: A total of 898 patients with intellectual disability had died over the 18 year study period. The all cause specific Standardised Mortality Ratios were 2.4 (95% CI=2.12.6) and 3.0 (95% CI=2.63.3) for males and females respectively. 244 of deaths occurred in people with a diagnosis of epilepsy rendering a Standardised Mortality Ratio of 3.2 (95% CI=2.63.8) for men and 5.6 (95% CI=4.66.7) for women. SUDEP Standardised Mortality Ratio was 39.6 for men (95% CI=23.163.4) and 52.0 for women (95% CI=23.7 98.8). The majority of these service users were male, of Caucasian ethnicity, and with a significant degree of intellectual disability (IQ<50). A significant number of patients had comorbid autism, physical and mental health problems, poorly controlled epilepsy and took more than one antiepileptic agent.

p273 COMPLEX PARTIAL STATUS EPILEPTICUS DUE TO HIPPOCAMPAL SCLEROSIS AS THE INITIAL MANIFESTATION OF PEDIATRIC-ONSET MIXED CONNECTIVE TISSUE DISEASE D. Athanasopoulos, D. Kitsos, E. Vasileiadis, and S. Giannakodimos General State Hospital of Athens, Athens, Greece
Purpose: Mixed connective tissue disease (MCTD) diagnosis is based on specific clinico-laboratory criteria with rare onset in childhood. We present a 16year-old adolescent with complex partial status epilepticus as the initial manifestation of pediatric-onset MCTD. Method: The patient was admitted following a prolonged (>12 hours) state of altered consciousness and disorientation, which ended up with two secondary generalized tonic-clonic seizures. Family/personal history for epilepsy was negative. No perinatal problems, febrile seizures or head trauma were reported. Result: Interictal EEG showed spikes/sharp waves over the left anteriortemporal regions and a 4sec duration paroxysmal generalized 3 Hz
81 Abstracts
spike-wake discharge. MRI-brain was compatible with left-sided hippocampal sclerosis (HS) (ipsilateral hippocampal and fornix atrophy, lateral ventricle dilatation and high T2/FLAIR signal of the hippocampus). On interviewing he reported muscle weakness and joint aches on the lower extremities. Physical examination revealed swollen fingers. Laboratory tests showed elevated CPK, positive anti-snRNP70 and ANA. Based on the Kasukawa criteria a definite MCTD diagnosis was made. Conclusion: Genetic or environmental factors may lead to hippocampal tissue injury and HS, evolving to mesial temporal lobe epilepsy (MTLE). Although MCTD-associated HS has not been reported, Central Nervous System (CNS) may be affected via vascular or inflammatory mechanisms, leading to early neurological manifestations. Correlation of MCTD with anti-SSA/ro seropositivity with neurological manifestations is already established. We hypothesize on probable similarities with Systemic Lupus Erythematosus regarding vasculitis-induced CNS involvement and HS development. Our case indicates that MTLE may be a consequence of MCTD. Should HS is revealed an underlying vasculitic mechanism could be hypothesized. Results: Patients were investigated by clinical examination, neuropsychological test, brain computed tomography, vascular related blood tests, EEG studies, angio MRI in selected cases. We find 72% generalized seizures and 28% focal seizures. Among generalized seizures 74% had only seizures and headache with no neurological objective signs. Regarding the etiology of these cases we find: tumors 6.3%, silent cortical ischemic lesions 6%, unexplained sequel lesion (porencefalia) 3.6%, no imagistic lesion 71% and focal vascular lesion in 13% (dural sinus thrombosis 49%, cerebral cavernous malformation 30%, cerebral vascular aneurysm 21%). We describe the 2 cases of female patients with generalized seizure as first neurological manifestation due to a frontal cavernoma and to a longitudinal sinus thrombosis with no objectives neurological signs. EEG revealed synchronous paroxysm of generalized polyspikes and the MRI angiogram detected 2 type of focal vascular impairment. Conclusion: Despite the focal vascular lesions, the existence of clinical first manifestation as primary generalized seizures must underlie a complementary, still unknown, pathological mechanism.
p274 STATUS EPILEPTICUS AND MULTIPLE SCLEROSIS CASE OVERVIEW D. Sahovic, and Z. Savic Clinical Center University of Sarajevo, Sarajevo, Bosnia and Herzegovina
Purpose: To present the case of a patient with a several years history of multiple slerosis with sudden status epilepticus. Method: The patient is 41 years old, with a 12-years clinical history of multiple sclerosis. The patient was treated and monitored well, and did not show any symptoms of any form of epileptic seizure. She suddenly presented a partial motor seizure with secondary generalization which evolved to the epileptic status of tonic and clonic spasms. Upon admission to the Intensive Care Unit, electroencephalographic investigations revealed EEG changes with specific epileptiform discharges (3.5 Hz S-W complexes) over the frontal lobe. EEG control showed normalization following medical therapy. Result: Since the previous treatment of the patient for the basis disease never revealed a possibility of developing of any form of epileptic seizure, a sudden and serious nature of her current status indicates the need for continuous caution and regular EEG monitoring of such patients. Conclusion: Multiple sclerosis patients may at any stage of the disease be at risk of a symptomatic form of epilepsy as an isolated seizure or a permanent form of epilepsy.
p276 ANTECEDENTS OF DRUG RESISTANT TEMPORAL LOBE EPILEPSY WITH AND WITHOUT HIPPOCAMPAL SCLEROSIS: A COMPARATIVE STUDY G. Shukla, and V. Goyal All India Institute of Medical Sciences, New Delhi, India
Purpose: To examine the role of initial precipitating events (IPE) in patients with drug resistant temporal lobe epilepsy (TLE) with and without hippocampal sclerosis. Method: Retrospective chart review of 171 patients diagnosed to have temporal lobe epilepsy based on clinical history, ictal video-EEG and MRI. Patients were categorized into two groups; [Group 1] with history of drug resistant TLE and MRI evidence of HS and Group 2 without HS, with or without other structural abnormality. Both groups were compared for age, gender, age at onset and duration of epilepsy, time to intractability, age at first febrile seizure (FS), frequency of FS, history of IPEs [including history of perinatal asphyxia, meningitis, encephalitis, head trauma], age at spontaneous remission. Statistical analysis was carried out using Mann Whitney test for continuous variables and Fisher's exact test for discrete variables (p Result: Seventy-two patients [24 female] with mean age of 26 + 11 years [range 8 to 55] fell in Group 1 with 99 patients [24 female] with mean age 21.6 + 10 years [range 3 to 60] in Group 2. Age at onset of epilepsy was significantly lower in Group 2 while a history of perinatal asphyxia and prolonged FS were more frequent in Group 2 (p Conclusion: A younger of age of presentation, (IPE) history of prolonged FS and a history of perinatal asphyxia were significant in patients with drug resistant TLE without hippocampal sclerosis. These findings raise the possibility of a distinct subgroup of patients with TLE who are treatment resistant with an early onset of epilepsy.
p275 GENERALISED SEIZURES AS FIRST CLINICAL MANIFESTATION OF DIFFERENT FOCAL CEREBROVASCULAR IMPAIREMENT D. I. Cuciureanu University of medicine Gr T Popa, IASI, Romania
Purpose: Background: To characterize and discuss an unusual etiology for generalized seizures in a small series of cases. Methods: We reviewed the clinical features and laboratory data of 1120 patients hospitalized for epilepsy in our neurological service during past 5 years, and we emphasize 2 cases with generalized seizures as first clinical manifestation of different focal cerebrovascular impairment.
p277 TREATMENT EFFICACY OF SYMPTOMATIC EPILEPSY IN POST STROKE PATIENTS H. D. Hambardzumyan, and H. M. Manvelyan Yerevan State Medical University, Yerevan, Armenia
Purpose: Post stroke patients often develop not only physical or motor impairment, but also cognitive decline and in some cases, mainly associated with cystic transformation of the brain tissue, they develop epileptic seizures also.
82 Abstracts
The aim of this study is effective treatment of post stroke patients with symptomatic epileptic seizures. Method: 27 patients (12 women and 15 men) of the age of 62 6 years, who met selection criteria: arterial hypertension, ischemic stroke, intracerebral cyst verification by MRI or CT scans and symptomatic epilepsy, were selected for this study. All of them had at list one seizure and positive EEG. Result: Cognitive impairment was assessed by modified Wechsler scale (71 point maximum), was in range of 33 8. 13 out of 27 patients took Carbamazepin 600 mg daily, in two months of observation period they were free of seizures, but the Wechsler score decreased till 28 6. 14 patients took Gabapentine 900 mg daily, in two months period they were free of seizures also, and Wechsler score was 32 6. Conclusion: Both medications in mean therapeutic doses are effective in prophylaxis of seizures in post stroke patients, but Carbamazepin causes decline in cognitive function in two months, whether patients on Gabapentine kept cognition level constant. The choice of medication in treatment of post stroke epilepsy must be done in accordance of their influence on cognitive functions also. Method: Observational case-control study (1:3) of patients with a nonlacunar acute cerebral infarct, seen in a Stroke Unit (20082009). Cases: patients treated with IV rt-PA. Controls: patients not treated with IV rtPA, paired with cases according to severity (NIHSS), and cerebral artery involved. Patients with previous epilepsy, brainstem infarct, or neurointerventionist treatment, were excluded. Variables: basal data, stroke severity (NIHSS), etiology, involvement of cerebral cortex and appearance of early (<7 days) or late (>7 days) symptomatic seizures. Result: 147 patients, 49 cases. Mean age was less in cases than in controls (66.51 Vs 72.78; p = 0.007). Proportion of males was similar (57.1% Vs 44.9%; p = 0.162). Cases had more frequently uncommon etiology infarcts (14.3% Vs 4.1%; p = 0.042). There were no differences in vascular risk factors, previous treatment, nor cerebral cortex involvement. Early and late seizures were similar between cases and controls (6.1% Vs 7.1%, and 10.2% Vs 7.1%, respectively; p=NS). Hemorrhagic transformation was the only independient predictor factor in early (OR 5.69; CI 90% 1.4422.45) and late (OR 3.71; CI 95% 113.76) seizures, adjusted by age, sex, NIHSS, cerebral cortex involvement and IV rt-PA. Conclusion: Treatment with IV rt-PA doesn't influence in the development of symptomatic seizures after an acute cerebral infarct. Hemorrhagic transformation is a predictor factor of such seizures.
p278 COMPARISON OF SOMATIC COMORBIDITY INCIDENCE IN YOUNG ADULTS WITH IDIOPATHIC AND SYMPTOMATIC EPILEPSY L. B. MarYenko, and K. M. MarYenko Lviv, Ukraine
Purpose: To compare the frequency and variety of somatic comorbidity in young adult patients with idiopathic (IE) and symptomatic epilepsy (SE) and duration of the disease more than 5 years. Method: We followed up (in the course of 510 years) two groups of patients aged 1840 years: 38 persons with IE (12 males, 26 females) with persistence of seizures from childhood or adolescence and mean duration of the disease 13.7 years and 94 persons (47 males, 47 females) with SE and mean duration of the disease 9.7 years. Complete clinical neurological and somatic examination with adequate para-clinical investigations were used to confirm the presence of somatic pathology. Result: In patients with IE somatic diseases were found in 50.0% of males and 42.3% of females, in SE patients in 53.2% and 72.3% accordingly. The most common somatic comorbidities in SE group were chronic ENT diseases (20.2%), GIT pathology (20.2%), ANS disorders (7.4%), urological (6.4%) and skin and joints diseases (3.2%). In patients with IE the most frequent pathology was endocrine one (especially menstrual disorders in females) 15.8%, ENT (13.2%) and GIT diseases (7.9%) as well as migraine (7.9%). Females with IE have higher frequencies of menstrual disturbances and polycystic ovaries than women with SE (t= )1.99, p 0.05), which may be explained by usage of valproates. Women with SE have higher incidence of other somatic comorbidities (t=)2.61, p 005). Conclusion: A high percentage of patients with epilepsy have somatic comorbidity, which should be taken into account while selecting an appropriate AED treatment.
p280 EPILEPSY ASSOCIATED WITH CEREBROTENDINOUS XANTHOMATOSIS SUCCESFULLY TREATED BY CHENODEOXYCHOLIC ACID P. Vrielynck*, A. Marchese, D. Roland, F. Linard, S. Andries, S. Ghariani, and K. Van Rijckevorsel *Centre Neurologique William Lennox, Ottignies, Belgium; Centre Neurologique William Lennox, Reference Center for Refractory Epilepsy, Universit Catholique de Louvain, Ottignies, Belgium; and Institut de Pathologie et de Gntique, Gosselies, Belgium
Purpose: Cerebrotendinous xanthomatosis (CTX) is a rare autosomic recessive metabolic disease causing cholesterol and cholestanol accumulation in multiple tissues. Clinical phenotype is variable, includes progressive neuropsychiatric deterioration. Epilepsy could occur in up to 50% of patients. Chenodeoxycholic acid (CDCA) may lead to clinical improvement. Here we describe electro-clinical evolution of epilepsy associated with CTX in a young male patient . Method: The patient was seen for the first time at our clinic at 16 yearold. He presented with mental retardation, behavioral disturbance, ataxia, peripheral neuropathy, bilateral cataract and epilepsy. MRI showed multifocal lesions of white matter. Cholestanol elevation in blood and CYP27A2 homozygous mutation (c. 1263 + 1 G>A) were found, establishing diagnosis of CTX. 24 hour EEG was performed before and after CDCA introduction. Result: Between 6 and 14 months, the patient had frequent bilateral myoclonia leading initially to diagnosis of benign myoclonic epilepsy, with good response to valproate. At 12 years, different seizures types occurred: myoclonia, generalized tonic-clonic and drop attacks. EEG showed diffuse slowing of background activity and diffuse polyspikes during wake and sleep, sometimes associated with myoclonia. Seizures became resistant to lamotrigine, levetiracetam and topiramate. CDCA was introduced at 17 years. A few months later, neuropsychiatric status improved, myoclonia and tonic-clonic seizures disappeared and frequency of drop attacks decreased to less than one episode per month. Three years later, improvement persists. Epileptiform discharges have disappeared on wake and sleep EEG . Conclusion: CTX is a rare cause of generalized symptomatic epilepsy. Early diagnosis and treatment may improve neurological status and epilepsy.
p279 FIBRINOLYSIS AND SYMPTOMATIC EPILEPTIC SEIZURES: PREVENTION OR INDUCTION M. J. Aguilar Amat Prior Hospital Universitario La Paz, Madrid, Spain
Purpose: Evaluating if intravenous (IV) treatment with rt-PA influences in appearance of symptomatic epileptic seizures after acute cerebral infarct.
83 Abstracts
p281 EPILEPSY IN PATIENTS WITH TUBEROUS SCLEROSIS COMPLEX S. T. Ristic*, D. T. Ristic, I. Marinkovic, and G. Djordjevic* *Clinical Centre of Nis, Nis, Serbia; Institutae of Pulmonary Disaeses, Nis, Serbia; and Medical Faculty of Nis, Nis, Serbia
Purpose: Tuberous sclerosis complex (TSC) is frequently associated with refractory seizures and development delay in children. Our purpose is to analyse epilepsy, AEDs (antiepileptic drags) therapy and cognitive development in adult patinets with TSC. Method: We revised data of 3 patients with TSC (diagnostic criteria revised by Gomez, 1999), with respect to the onset, type of epilepsy, neuroimaging, cognitive and mental alteration (using the Griffiths Mental Development Scales, 1996. god. Revison), response to antiepileptic therapy. Result: First patient is a 47 year old women, with typical skin abnormalities: hypomelanotics macules (more than three), shagreen patch, nontraumatic peringual fibromas and typical three types of brain tumors: cortical tubers, subependymal nodules and subependymal giant- cell astrocitomas. She has low cognitive potentials and refractori partial epilepsy with secondary generalisation. Second patient is 25 year old man, with litle skin abnormalitis (hypomelanotics macules and periungual fibromas), typical brain tumors (cortical tubers, subependymal giant-cell astrocitomas), low cognitive potencials end refractori partial epilepsy without secondary generalisation. Third patient is 51 year old women with facial angiofibromas and typical three types of brain tumors (cortical tubers, subependymal nodules and subependymal giant- cell astrocitomas), low cognitive potentials and refractori partial epilepsy with secondary generalisation. Conclusion: We discussed clinical caracteristic, diagnostic and therapeutic diferences. All patients have multiple lesions. Epilepsy began as partial seizures with secondary generalisation in 2 patients and one patient had complex partial seizures. All patients have global intelectual impairmant. One patient with monotherapy is seizure free while 2 patients with polytherapy have a reduction of seizure frequenty and intensity. Conclusion: MTLE may be a characteristic manifestation of NPSLE. Most previous reports indicate that generalized seizures occurs often epilepsy in SLE, and a few reports indicate that partial or focal seizures are frequent. However it is possible that most of generalized seizures in SLE reported before could in fact be focal epilepsy with secondarily generalized seizures. MTLE is therefore an important differential diagnosis in NPSLE patients with seizures.
Semiology, Aetiology and classification 7 Monday, 01 October 2012

p283 AN ASSESSMENT OF THE INTER-OBSERVER RELIABILITY OF THE DEFINITION OF DRUG-RESISTANT EPILEPSY PROVIDED BY THE INTERNATIONAL LEAGUE AGAINST EPILEPSY L. H. Ronquillo, L. Hernandez-Ronquillo, R. S. Topete, and S. Buckley University Of Saskatchewan, Saskatoon, Canada
Purpose: To evaluate the inter-observer reliability of the definition of drugresistant epilepsy provided by the International League Against Epilepsy (ILAE). Method: We randomly selected ninety-seven charts from 700 available from the epilepsy clinic of the Royal University Hospital in the province of Saskatchewan, Canada (1 million population). Two independent chart reviewers underwent training regarding the four definitions of intractable epilepsy used in this study. Both individuals performed a small pilot with 10 charts. None of the reviewers knew the patients and the evolution of the cases. We used the definition of drug-resistant epilepsy published by Kwan and Brodie, Berg, Camfield and the one provided by the ILAE. The reviewers abstracted demographic data, diagnostic of epilepsy, classification, evolution and medications. After the extraction of the necessary clinical information the four definitions were applied. Charts were reviewed with less than two months difference between reviewers to avoid misclassifications of patients over the time. Kappa was used to compare the agreement between observers. Results: The kappa for the Berg's definition was 0.56 (moderate), for the Kwan and Brodie's definition was 0.58 (moderate), for the Camfield's definition 0.69 (substantial) and for the definition of the ILAE was 0.77 (substantial). Other analysis will be shown in the meeting. Conclusion: The definition of drug-resistant epilepsy provided by the ILAE showed the best agreement between observers. Both observers considered that the definition of the ILAE was more complex to extract than the other three definitions due to the need of more information.
p282 MESIAL TEMPORAL LOBE EPILEPSY AS A NEUROPSYCHIATRIC SYNDROME OF SYSTEMIC LUPUS ERYTHEMATOSUS T. Toyota, N. Akamatsu, A. Tanaka, T. Shouzaki, and S. Tsuji University of Occupational and Environmental Health School of Medicine, Kitakyushu, Japan
Purpose: Different types of seizures are grouped together without distinction from epilepsy in the standard nomenclature and case definitions for neuropsychiatric syndromes of systemic lupus erythematosus (NPSLE) which has developed by the American College of Rheumatology. We aimed to investigate the types of seizures and epilepsy associated with systemic lupus erythematosus (SLE). Method: We searched the medical records at a tertiary referral center to identify a cohort of epilepsy patients with SLE who were treated between January 2000 and August 2011. We analyzed the clinical and immunological profile of these patients, their seizure and epilepsy classifications, electroencephalography and MRI assessments, and the treatment administered for epilepsy and SLE. Result: Seventeen patients with SLE and epilepsy were identified. Seven patients had mesial temporal lobe epilepsy (MTLE), 8 had epilepsy secondary to stroke, and 2 had generalized epilepsy. Of the 7 patients with MTLE, temporal spikes were noted in all patients on EEG and, MRI findings suggesting hippocampal sclerosis was noted in 4. Clobazam and levetiracetam were effective in treating 3 patients, and 1 underwent amygdalahippocampectomy.
p284 EPILEPSY AMONG THE STUDENTS OF ANAKKALE ONSEKIZ MART UNIVERSITY H. I. Ozisik Karaman, C. Bakar, and Y. Degirmenci Canakkale Onsekiz Mart Universitesi, Canakkale, Turkey
Purpose: Aim of this study was to investigate the frequency epilepsy among the students of Canakkale Onsekiz Mart University. Method: This sectional epidemiological study was performed on 4762 of the 19988 Canakkale Onsekz Mart University students in 20072008 education period. Participants who answered epilepsy to the question Do you have any disease disgnosed by a doctor? in a questionnaire including 4 subgroups were detected. Data were transferred to Epi-Info Version 6.0 statistics program and controlled data were analyzed in SPSS 15.0 statistics program.
84 Abstracts
Result: Fifty three point one percent of the students were female, 46.9% were male. Mean age was 20.4 2.1 years. Twelve (0.3%) students had epilepsy diagnosis. Among these, 66.7% were female (n = 8), 33.3% (n = 4) were male and the mean age was 20.8 1.8 years. Conclusion: In our study, epilepsy was detected in 0.3% of the students (n = 12). Conclusion: We didn t encountered any data for this age group in our literature review for epilepsy which has a variable frequency for age and counttries. Thus, we considered that it would be epidemiologically significant to share the results of our cross sectional study. deities such as Apollo the physician or the supreme Egyptian god Ammon (the occult). Greek and Roman deities and their artistic representation date indeed back to Ancient Egyptian times. Depicted with a rams horn, Ammon was adopted by the Greeks as Zeus and later by the Romans as Jupiter. A transition that can be found in Greek coinage devoted to Alexander the Great as well as in provincial Roman coins struck under Claudius. Result: Inspired by the Renaissance school of Padua French anatomists continued to recover gods and myths of Classical Antiquity during the Enlightenment, renaming brain structures like the curve shaped inner portion of the temporal lobe as Cornu Ammonis. Among the most remarkable contemporary neuroscientists who studied this hidden part of the brain outstands Cajal and his disciple Lorente de N, who described the tri-synaptic circuit and the different CA (Cornu Ammonis) fields within. CA1 is also known as Sommers sector to acknowledge the latter description of mesial temporal sclerosis in temporal lobe epilepsy. Conclusion: Ancient Greek and Roman coinage illustrate the role that myths and gods of Classical Antiquity keep playing in modern neurology.
p285 KNOWLEDGES AND BELIEVES OF PARENTS OF CHILDREN AND ADOLESCENTS WITH EPILEPSY B. Desnous, M. Milh, and S. Auvin Robert Debr Hospital, Paris, France
Purpose: We conducted a survey in order to determine the level of knowledge that parents of children with epilepsy have about epilepsy: what the epilepsy is for parents, we wanted to assess if they know how epilepsy's diagnosis is made. This study aimed to know the endpoints of seizure's severity, the seizure's trigger, and the concerns during seizure for parents. This study also aimed to highlight the impact of epilepsy in lifestyle of children and their parents. Method: We conducted a qualitative survey, based on semi-structured interviews with parents of children with epilepsy between April and November 2010 in paediatric neurology department in 4 French university hospitals: Amiens, Marseilles, Nancy and Robert Debr Hospital (Paris). Physicians conducted all the interviews. Parents of children with epilepsy were interviewed: 34 relatives aged 0 to 6 years, 38 relatives aged 7 to 12 years and 34 relatives aged more than 12. In total 106 interviews were conducted. Result: This study allows assessing the knowledge and believes of parents of children and adolescents with epilepsy and showed that knowledge of epilepsy among parents was generally limited. On average 34% of parents were unaware of their children's cause of epilepsy. Regarding to the endpoints of seizure's severity, the main criteria for all parents is the duration of the seizure. The anti epileptic drugs have a positive image to parents; they are with psychological support and lifestyle the three main points of their child's treatment. Parents confirm that epilepsy has a strong impact on their child's lifestyle. Conclusion: So many patients, parents of children with epilepsy are not well informed about their disorder. There is slightly a need for educational intervention to optimize self-management strategies. An understanding of preseizure activity from the patients and carers perspective has great utility if the information can be combined with more objective data to identify gaps in patients and carers knowledge, which can then be used to develop education and intervention programs. Parents are reassured by a medical team that treats the whole child and not just epilepsy.
p287 AUDIT OF LOCAL NEUROPATHOLOGY PRACTICE IN SUDEP AUTOPSIES M. Thom*, J. Liu*, J. W. Sander, and S. M. Sisodiya *UCL, Institute of Neurology, London, UK; Heemstede, Netherlands; and UCL Institute of Neurology, London, UK
Purpose: There is an urgent need to understand the underlying mechanisms of sudden and unexpected death in epilepsy (SUDEP). Research based on post mortem (PM) brain collections may identify novel pathological and molecular mechanisms. This necessitates collection of a sufficient numbers of adequately sampled cases with complete clinical and post mortem reports. Method: We audited all epilepsy PMs at our centre for the completeness of data and regional brain sampling. We re-classified SUDEP cases according to revised definitions [Epilepsia 2011]. Questionnaires were also sent to local general histopathologists (HP) regarding current practice in epilepsy related deaths. Result: We identified 62 SUDEP PMs (from 1991 to 2011), the majority referred cases for neuropathology examination. The median age at death was 24 years (range 279 years); 38 in males. The few cases with inadequate regional brain sampling were those where the whole brain had not been fixed. Neuropathological changes were identified in the majority of cases, hippocampal sclerosis the commonest finding in 25. Cases were re-classified as possible SUDEP where full PM report was lacking or contributing cause of death identified. Reponses from HPs indicated that of those that conduct PMs, 70% virtually never retain the whole brain in epilepsy related deaths. Conclusion: Systematic sampling in SUDEP brain demonstrates frequent neuropathological abnormalities and provides a useful research resource. We highlight the importance of complete PM reports for correct classification SUDEP and the need to increase awareness among HPs of the value of a complete neuropathological examination.
p286 ON THE ORIGIN OF CORNU AMMONIS (AMMON'S HORN) I. Iniesta The Walton Centre NHS Foundation Trust, Liverpool, UK
Purpose: To investigate the origin of the term Cornu Ammonis (Ammons horn), introduction in medical literature and current meaning. Method: As primary historical sources, Greek and Roman coins are essential archaeological remains that inform about the myths and gods of Classical Antiquity, from the arrival at Rome of a snake shaped god Aesculapius to save the Italians from the plague to invocations of major
p288 FUNCTIONAL ASYMMETRY OF THE BRAIN AND LATE COMPONENTS OF EVENT-RELATED POTENTIAL P300 O. S. Ivetic, and V. Vasic Medical Faculty, Novi Sad, Serbia
85 Abstracts
Purpose: The aim was correlation of the brain lateralization and variables of cognitive P300 potentials during the usage of arms among righthanded girls. Method: 60 right-handed girls, age 2024, participated in investigation. First group: strong expressed right-hand girls; second group: moderately expressed right-hand girls; third group: right-hand learned girls. The research workers were using the "oddball paradigm with two tones:"standard and "expected-target. The subjects got instructions to press a button, as fast as they can, whenever they hear the expected tone. The response was measured with the use of the right hand (firstrecording) and left hand (second-recording). P300 evoked potentials were registered above Fz and Cz area. Result: It was shown that subjects with higher degree of dominance of the left brain hemisphere have significantly shorter latencies and higher amplitudes of P300 when the dominant hand was used, while the subjects with weak or average degree of dominance of the left brain hemisphere show no significant difference. Cognitive P300 amplitude waves are higher above central regions independently of the hand used. Also, subjects with higher degree of dominance of the left brain hemisphere had shorter RT but the difference was not statistically significant. The number of false response was higher in right-hand learned girls. Conclusion: The hemispheric dominance has influence on the eventrelated potential.
*I. Beritashvili Center of Experimental Biomedicine, Tbilisi, Georgia; and Institute of Neurology and Neuropsychology, Tbilisi, Georgia
Purpose: Epilepsy is found in 0.88% of Georgian population. Sleep disorders are common conditions that frequently coexist with epilepsy. The present study was aimed to identify insomnia and restless legs syndrome (RLS) in treated epilepsy patients (T) and newly diagnosed individuals having epilepsy (UT). Method: Among the 161 consecutive subjects admitted to the Institute of Neurology and Neuropsychology, 119 had epilepsy diagnosis treated with antiepileptic drugs (AEDs) and 42 were newly diagnosed epilepsy patients never taken AEDs before. Sleep impairment index was filled out by 84 subjects (60, T and 24, UT), group 1, and the questionnaire for the RLS was completed by 77 subjects (59, T and 18, UT), group 2. Data analysis was performed by SPSS statistical software, version 13.0. Result: Among the 161 consecutive subjects admitted to the Institute of Neurology and Neuropsychology, 119 had epilepsy diagnosis treated with antiepileptic drugs (AEDs) and 42 were newly diagnosed epilepsy patients never taken AEDs before. Sleep impairment index was filled out by 84 subjects (60, T and 24, UT), group 1, and the questionnaire for the RLS was completed by 77 subjects (59, T and 18, UT), group 2. Data analysis was performed by SPSS statistical software, version 13.0. Conclusion: These findings clearly indicated that the understanding the relationship between epilepsy and sleep disorders is important for the developing of appropriate treatment strategy for the epilepsy patient.
p289 PHARMACO-RESISTANT EPILEPSY-CASE PRESENTATION C. Panea, G. D. Vanghelie, N. Ploscutanu, and G. Cioara Emergency University Hospital Elias, Bucharest, Romania
Purpose: Drug-resistant epilepsy is defined as the persistence of seizures despite adequate antiepieleptic treatment with at least two first-line AEDs, monotheraphy or in combination, using different mechanisms of action and at maximum tolerated doses. Method: Pseudoresistance must be also taken into consideration, in which seizures persist because the underlying disorder has not been appropriately diagnosed and treated or misdiagnosis of epilepsy with other conditions that mimic epileptic seizures (vasovagal syncope, cardiac arrhythmias, metabolic disturbances, transient ischemic attacks, migraine, psychogenic seizures that are estimated to account for more than 25% of adult cases of apparently drug-resistant epilepsy). Result: We present the case of a 33 years old male, diagnosed with focal epilepsy with complex partial seizures and secondary generalization that was considered to be resistant to antiepileptic drugs, with positive family history (his brother has idiopathic primary epilepsy), cerebral imagery that revealed hippocampal asimmetry and right frontal angioma and an interictal EEG that did not allow a certain diagnosis as regarding the type of epilepsy. Ictal recordings showed an EEG ictal pattern with its onset on the left temporal and fast propagation to the right fronto-temporal with secondary generalisation. Conclusion: Possible clinical predictors of drug resistance have been identified including a high number or frequency of seizures in the early phase of the disorder and a presence of a structural cause of epilepsy, particularly hippocampal sclerosis. For this case, it is imposed to asses the benefit-risk of treatment alternatives that should also consider epilepsy surgery.
p291 NEUROAMINOACIDS STATE IN PATIENTS RECOVERING FROM TRAUMATIC BRAIN INJURY WITH CONVULSIVE SYNDROME I. I. Chernenko*, and N. Sych *Kharkiv Medical Academy of Postgraduate Education, Kharkiv, Ukraine; and Institution, City, Russian Federation
Purpose: The aim of work was to study the content neuroaminoacids (NAC) in whey of blood patients with traumatic brain injury (TBI) with a convulsive syndrome. Method: Material and methods. We examined 42 patients with TBI at the age of 23 to 65 years. The level of NAC was determined in the first days after TBI received. The first group consisted of 20 persons moderate TBI with convulsive syndrome, mean age 53,39 0,42 years, the second 22 people with mild TBI with a convulsive syndrome, mean age 52,71 0,49 years. The groups were comparable in age, sex. Result: The results. The study revealed that patients with mild TBI level of excitatory NAC (glutamic 1,145 0,24 mg, aspartic 0,228 0,05 mg) were significantly higher than in patients with moderate TBI with convulsive syndrome (0,805 0,07 mg and 0,164 0,02 mg, respectively), p < 0,05. At the same time, there was a trend to an increase in brake NAC in patients with mild TBI with a convulsive syndrome compared with patients with moderate TBI with a convulsive syndrome (glycine 1,427 0,13 mg and 1,345 0,19 mg respectively, proline 1,556 0,24 mg is the 1,211 0,17 mg, respectively), p > 0,05. Conclusions: Thus, patients with mild TBI with a convulsive syndrome marked by an imbalance of NAC: NAC increase in excitatory (glutamate, aspartate) and a tendency to increase the level of brake NAC (glycine, proline) compared with patients with mild TBI with convulsive syndrome.
p290 ANTI-EPILEPTIC THERAPY AND SLEEP RELATED PROBLEMS IN GEORGIAN EPILEPSY PATIENTS L. Maisuradze*, L. Zhizhiashvili, and S. Kasradze
86 Abstracts
p292 EPILEPSY AND NEUROCYSTICERCOSIS IN NORTH WEST CAMEROON: A SEROLOGICAL STUDY A. J. Akeneck, C. O. Snead, I. E. Elliott, N. K. Alfred, A. S. Angwafor, L. C. Cockburn, I. T. Takougang, and M. L. Lou Association of Orphans and the Disabled ASODI Cameroon, Mankon Bamenda, Cameroon
Purpose: The prevalence of epilepsy in Cameroon is higher than that of the industrialized?world. The prevalence of epilepsy appears to be especially high in the Momo Division of the Northwest Province of Cameroon. Because neurocysticercosis is a major cause of epilepsy in developing countries, we sought to test the hypothesis that those patients in Momo who have epilepsy have a higher percentage of seropositivity to Taenia solium than a matched control population. A case control study was conducted in the Momo sub-division of Ngie which has nineteen villages. Epilepsy patients were recruited from the epilepsy clinics in Ngie and control subjects were randomly selected from members of the Ngie villages. An adapted form of a previously validated screening questionnaire was applied by trained field workers to identify potential cases of epileptic seizures to be included in the study. Blood samples were taken from all consenting individuals by finger prick, stored in StabilZyme Select, and assayed for antibodies to Taenia soleum as described. Method: This study was carried out under the ethical precepts found in the World Medical Association Declaration of Helsinki (http:// www.wma.net/e/policy/b3.htm). Ethics approval was obtained from the Research Ethics Board (REB) of the Hospital for Sick Children, Toronto, Canada, the National Ethics Committee, Cameroon, and the local district ethics committee, Alpha Royal Clinic REB. Community consent was first obtained by having medical health volunteers explain the goal of the study to village traditional and administrative and health authorities. Community information sessions were then conducted, the purpose of which was to allow individuals to discuss their questions and concerns. Village coordinators, who helped study participants to complete the questionnaires, were trained on how to obtain informed consent. In addition, the coordinators determined who could read. Ngie language is not written. Therefore, to make things clear a translated version of the informed consent was made on an audiotape and played where necessary. Following these community meetings, potential subjects and controls were provided further information and if they agreed to participate, consent for the administration of the questionnaire and blood sampling was obtained. Result: We accrued 249 patients with epilepsy and 245 age-matched controls. The number of patients with epilepsy who participated in this study represent about 75% of the total number of seizure patients in Ngie where the population is around 40,000 inhabitants. The mean age of control subjects was 17.5 years and that of the seizure population 18.8 years (P > 0.1). There were 53% male and 47% female in the seizure group and 57% male and 43% female in the control group (P > 0.1). Seizure onset was at 11.64 yrs. Sixty-eight percent of patients had generalized convulsive seizures with 25% having localization-related epilepsy with secondary generalized seizures. There was no significant difference between the control and seizure populations in seropositivity to Taenia soleum which was 4.9% in the control group vs. 5% in the seizure group. These data demonstrate that those patients in the Ngie sub-division of Momo who have epilepsy do not have a higher percentage of seropositivity to Taenia solium than a matched control population and make it highly unlikely that neurocysticercosis plays a causative role in the increased prevalence of epilepsy in the Momo Division of the Northwest Province of Cameroon. Supported in part by The Bloorview Children's Hospital Foundation. Conclusion: This data does not support the hypothesis that those individuals in Ngie sub division of Momo Division who have epilepsy have a higher percentage of teania solium than a matched contro population. The data makes it highly unlikely that neurocysticercosis plays a causative role in the increased prevalence of epilepsy in the sub region. These results and preveiousely published results suggest that the high prevalence of epilepsy reported in some areas in Cameroon could be attributed to a complex yet to be elucidated, interplay of several factors.
SEMIOLOGY, AETIOLOGY AND CLASSIFICATION 8 MONDAY, 01 OCTOBER 2012 p293 HEALTH-RELATED QUALITY OF LIFE OF PATIENTS IN THE PATIENTSLIKEME EPILEPSY COMMUNITY C. De La Loge*, S. Dimova, K. Mueller, T. Durgin, M. Massagli, and P. Wicks *UCB Pharma, Brussels, Belgium; UCB Pharma SA, Brussels, Belgium; UCB Pharma Monheim, Monheim, Germany; UCB Pharma SA, Smyrna, GA, USA; and PatientsLikeMe Inc, Cambridge, MA, USA
Purpose: To describe health-related quality of life (HRQoL) of members of the PatientsLikeMe Epilepsy Community and identify predictors of poor HRQoL. Method: Analyses were based on patient-completed information: sociodemographic and disease characteristics, treatments, symptoms, seizure occurrence, Quality of Life in Epilepsy (QOLIE-31/P) and Hospital Anxiety and Depression Scale (HADS). Result: By May 2011, 1025 patients had completed the QOLIE-31/P and HADS and were included in this analysis (mean age 37.5 years; 72.7% female; mean epilepsy duration from diagnosis 17.5 years). HRQoL was highly correlated to HADS Anxiety and Depression scores. Poor HRQoL was more likely in patients reporting (Odds Ratio [95% Confidence Interval]; multivariate logistic regression): i) moderate/ severe problems concentrating (3.19 [2.005.08]), depression (2.61 [1.773.85]), memory problems (2.04 [1.293.24]), fatigue (1.75 [1.12 2.71]), anxiety (1.49 [1.002.22]); ii) severe side effects (2.34 [1.39 3.92]); iii) at least one tonic-clonic seizure during the 4 weeks before QOLIE-31/P completion (2.72 [1.654.50]); iv) age 2550 years (1.77 [1.013.11] vs age 025 years) and v) shorter epilepsy duration (1 year 2.25 [1.234.13]; 110 years 1.70 [1.122.58]; both vs >10 years). Patients on polytherapy with newer antiepileptic drugs (AEDs) were less likely to report poor HRQoL than patients on polytherapy with older AEDs (0.29 [0.110.74]). Conclusion: These analyses indicate that moderate/severe problems concentrating, depression, and the occurrence of generalized tonic-clonic seizures and severe side effects were the most predictive factors of poor HRQoL in the PatientsLikeMe Epilepsy Community. These results suggest that a holistic approach beyond seizure control should be considered when treating people with epilepsy.
p294 EVALUATING EPILEPTIC POPULATION AND ITS COST IN THE SOUTH OF SPAIN G. Garcia Martin, M. I. Chamorro Muoz, M. Romero Acebal, and F. Perez Errazquin Virgen de la Victoria Hospital, Malaaga, Spain
Purpose: Epilepsy is a common disorder around the world and a big effort in order to know the features of the population with this illnesss is being done nowadays. Although there is quite information of some parts of Europe, information from the south west is not enough. Moreover knowing the cost of the illness is really interesting in the current economic situation. The purpose weas to evaluate the features of people with epilepsy in Malaga (Spain) and the cost of visiting this population in a General Hospital. Method: To describe the features of all the patients with active epilepsy or epilepsy on treatment visited in Virgen de la Victoria Hospital in Malaga, in one of the Epilepsy Offices. To calculate the cost of epilepsy taking into account number of visits, tests made and the consumption of drugs in one year but not emergency assistance.
87 Abstracts
Result: 515 patients were selected of a total of 2282 patients visited in all the Epilepsy Offices. Features of patients and the costs of illness are presented. We compare our results with those from other studies in Europe. Conclusion: The features of the epileptic population in Malaga are similar to those from other parts of Europe. The cost of epilepsy in our Hospital is quite similar to that of other studies in Europe. The main cost in Hospitla for this population depends on the nmumber of visits to the neurologist and on the chronic treatment. epilepsy; individual epilepsy management; and aspects of epilepsy that matter most to people with epilepsy. During July-October 2011, 513 people with epilepsy (63.8% female; ages ranging from <16 to >65 years) from 29 countries completed the survey. All survey responses were anonymised and collated in a central database for analysis. Result: Over 60% of respondents considered their seizures to be sufficiently controlled, but >40% still had seizures at least every month and >40% would have changed medication to improve seizure control. Approximately 70% of respondents suffered medication side effects and >30% would have changed medication to reduce side effects; however, almost 25% had never proactively discussed side effects with their doctor/nurse. Different side effects mattered more/less to different respondents (e.g. weight gain tended to matter more to females than males). Approximately 30% of respondents admitted missing medication at least once a month. Conclusion: The survey provides valuable insights into the real challenges and needs of people with epilepsy and may play a part in shaping future management strategies. Supported by Eisai.
p295 PSEUDO-REFRACTORY EPILEPSY: FOLLOW UP 105 PPATIENTS G. Kutlu, A. Erdal, Y. Bier Gmceli, and L. E. Inan Ministry of Health, Ankara Research and Training Hospital, Ankara, Turkey
Purpose: Pseudo-Refractory epilepsy is defined as seizures inadequately treated due to incorrect diagnosis, use of incorrect and/or low dose antiepileptic drug (AED) and poor compliance of patients. The aim of this was to investigate the patients with pseudo-refractory epilepsy. Method: The files of two thousand nine hundred twenty patients were reviewed by the same neurologist and the patients with pseudo-refractory epilepsy were eliminated. The patients who had not enough control of seizures despite the two different AED treatment before follow up in our department and had no seizure at least one year after the revision of the diagnosis and/or treatment of epilepsy, were accepted as pseudo-refractory. Demographic data, medical and epilepsy history, electroencephalography (routine and/or induction of seizure by using normal saline or self induction), home video and neuro-imaging findings were examined. Result: One hundred five patients were included in this study. The mean age was 29 11.53. Seventy-four patients (70.5%) was female, the remaining 31 patients were male. Incorrect diagnosis of epilepsy was observed in 57 patients (forty seven non-epileptic psychogenic seizure, seven syncope, two sleep disorder, one hypoglycemia). Epilepsy classification and treatment error was present in eighteen patients. Forty two patients had poor compliance of treatment and inappropriate life style. Twelve patients had more than one reason for pseudo-resistance (together with classification and/or treatment error, and poor compliance). Conclusion: Pseudo-refractory patients are still a big problem in our clinical practice. Differentiation of pseudo-refractory and true refractory epilepsy is so important for avoiding unnecessary treatment approach and future management of true refractory epilepsy.
p297 SOMATIC CO-MORBIDITIES ARE A MAJOR ISSUE IN PEOPLE WITH EPILEPSY J. Novy, G. Bell, S. M. Sisodiya, and J. W. Sander UCL Institute of Neurology, London, UK
Purpose: People with epilepsy seem to have more concomitant medical conditions than the general population. Co-morbid conditions may be a factor in the increased risk of premature death seen in people with epilepsy, including those in remission. While there are several studies exploring epidemiological patterns of psychiatric co-morbidities in epilepsy, less is known about somatic co-morbidities. We aimed to explore the epidemiology of somatic co-morbidities in people with epilepsy. Method: We collected clinical, demographic and somatic co-morbidity data in >2000 consecutive people with drug-resistant epilepsy assessed at a tertiary centre and in 1350 patients with epilepsy in the community. Underlying causes of epilepsy were not taken as co-morbidities, neither were symptoms of the cause. Result: Somatic co-morbidities were found in 48% of people with drugresistant epilepsy and in 35% in the community (p < 0.0001). People with drug-resistant epilepsy were younger (median age 35) than those in the community (median age 45). Somatic co-morbidities were more frequent than psychiatric ones (25% in people with drug-resistant epilepsy, 10% in the community). Preliminary analysis suggests that older age, older age at epilepsy onset and no identifiable cause may be independent predictors of a higher burden of co-morbidities. Conclusion: This seems to suggest that epilepsy itself influences the occurrence of somatic co-morbidities. Somatic co-morbidities should not be overlooked as they appear as frequent as psychiatric co-morbidities. The reasons for this are not entirely clear as this stage but common genetic predisposition cannot be discounted. Further studies are urgently warranted.
p296 WHAT REALLY MATTERS TO PEOPLE WITH EPILEPSY? RESULTS FROM AN INTERNATIONAL PATIENT SURVEY J. A. Cramer*, S. Dupont, M. Goodwin, and E. Trinka *Yale University School of Medicine, Houston, TX, USA; PitiSalptrire Hospital, Paris, France; Northampton General Hospital NHS Trust, Nothampton, UK; and Paracelsus Medical University, Salzburg, Austria
Purpose: To conduct an international survey amongst people with epilepsy, in order to define issues of importance in their daily lives, correlated with duration of epilepsy, age, as well as other characteristics. Method: A web-based survey, translated into 12 languages, was distributed through the International Bureau for Epilepsy member association websites and via email. The predominantly multiple-choice questionnaire focused primarily on personal experiences of the impact of
p298 DEVELOPMENT AND PILOT OF A QUESTIONNAIRE FOR REPORTING EPILEPSY-RELATED DEATHS L. Flores*, K. Osland, J. Hanna, and L. Nashef* *King's College Hospital, London, UK; and Epilepsy Bereaved, Oxfordshire, UK
Purpose: Aim: To assess the applicability of a detailed questionnaire administered by a lay person to bereaved relatives on sudden death in epilepsy.
88 Abstracts
Method: After basic training, the questionnaire, based on a previously used tool, was administered through telephone interviews carried out by two workers from Epilepsy Bereaved with relatives of deceased patients. Result: The survey obtained complete and detailed data on most items included. SUDEP was stated as the cause of death in 17 of 31 transcribed interviews, three with reportedly mild epilepsy, four with relatively recent onset of seizures and three witnessed cases. Three relatives reported having received some information about SUDEP from the medical team. More than half the families were not contacted by the medical team after death and counselling was offered to 15 only. Conclusion: The applicability of administering this questionnaire by a lay person familiar with the field was demonstrated. Data obtained was assessed as high quality with limited modifications to the questionnaire needed. This tool may be useful for a SUDEP register. The increase in death certificates listing SUDEP in 54.8% of cases compared to 3.8% (1/ 26) in an older study of circumstances of death in SUDEP carried out 16 years ago suggests a greater awareness by pathologists and coroners. On the other hand, counselling and a meeting with the treating specialist were reportedly infrequently offered.
*SEIN-Epilepsy Institute in the Netherlands Foundation, Heemstede, The Netherlands; Institute of Neurology, London, UK; and UCL Institute of Neurology, London, UK
Purpose: Postictal generalized EEG suppression (PGES) seems to be a pathophysiological hallmark in the ictal recordings of sudden unexpected death in epilepsy (SUDEP). It has recently been suggested that the presence and duration of PGES might be predictors of SUDEP risk [1]. Little is still known about its aetiology. Method: A retrospective case-control study was conducted in 50 people with convulsive seizures (CS) registered on digital video-EEG. Per individual one CS was reviewed for the presence and duration of PGES by two independent assessors: 37 (74%) patients showed PGES and 13 (26%) did not. Pre- and postictal heart rate (HR) and frequency domain measures of heart rate variability (HRV) including the ratio of low versus high frequency power were analyzed . The relation between PGES and peri-ictal autonomic changes was evaluated, as well as its association with several clinical variables. Result: PGES was neither associated with peri-ictal HR (mean HR difference between PGES+ and PGES- seizures: -5 bpm, 95% CI -13 to +3 bpm) nor HRV change. There was no relation between duration of the tonic-clonic phase of the seizure and PGES. Patients with PGES were more likely to be asleep prior to seizure onset (OR 4.7, 95% CI 1.218.3) and had a higher age of onset (median age; 15 vs. 5 years). Conclusion: PGES was not associated with substantial changes in measures of cardiac autonomic instability but more prevalent in CS arising from sleep. PGES might be an expression of excessive neuronal inhibition acting as a seizure termination mechanism. Reference: 1.Lhatoo SD, Faulkner HJ, Dembny K, Trippick K, Johnson C, Bird JM. An electroclinical case-control study of sudden unexpected death in epilepsy. Ann Neurol 2010; 68(6): 787796.
p299 PLACE OF VIDEO-EEG MONITORING IN DIAGNOSIS AND MANAGEMENT OF IDIOPATHIC GENERALIZED EPILEPSY L. Iuhtimovschi*, S. Groppa*, and A. Bunduchi *State Medical and Pharmaceutical University Nicolae Testemitanu, Chisinau, Moldova; and Medical Center Excellence, Chisinau, Moldova
Purpose: To appreciate electro-clinical correlations in patients with active focal epilepsy treated unsuccessfully with Carbamazepine. Method: Our study included 32 patients (21 women and 11 men), age range 1854, diagnosed with epilepsy 1,5 to 30 years ago, previously examined only by routine EEG (1015 minutes). All patients were evaluated by video-EEG monitoring 3 to 6 hours. Result: 13 patients had EEG electro-clinical patterns petit mal typical for absence epilepsy. 5 patients revealed electro-clinical patterns of myoclonic seizures. 14 patients presented subclinical discharges of typical generalized spike-wave, poly-spike-wave, and sharp wave-slow wave activity. All changes appeared on preserved general cortical activity. Accordingly patients were divided in groups: I group Absence epilepsy, II group Juvenile Myoclonic Epilepsy, III group Idiopathic Generalized epilepsy. In all patients treatment was substituted with Valproate (I, II, and III group) or Ethosuximide (I group). Video-EEG monitoring was repeated 4 month later. In 100% cases EEG revealed substantially reduced epileptiform activity. Follow-up period of 1,5 to 3 years showed clinical remission in 3 patients (I group), 2 patients (II group), and 7 patients (III group); while electro-clinical remission in 8 patients (I group), 3 patients (II group) and 5 patients (III group). Conclusion: Routine EEG investigations are insufficient for a clear diagnosis of idiopathic generalized epilepsy, because myoclonic and absence seizures are often neglected by patients and observers. When addressed to specialist patients present generalized seizures incorrectly diagnosed as secondarily generalized and treated with Carbamazepine. Video-EEG monitoring helps to establish epileptic patterns, correct diagnosis and initiate adequate treatment.
p301 AUTOMATIC ABNORMAL WAVES DETECTION FROM THE ELECTROENCEPHALOGRAMS OF EPILEPSY CASES TO SORT OUT THE SPIKES, THE SHARPS, THE POLYPHASE BASED ON WAVELET TRANSFORMATION CROSSCORELATION S. Noertjahjani UNDARIS, Semarang, Indonesia
Purpose: Wavelet transformation is applied to electroencephalogram records from epileptic patients. The temporal sharpness associated with interictal spikes at different resolutions is observed and two ways for representing the multiresolution sharpness of the spikes. Method: Patient consist of 349M, 234F, ages 368 years. Clinical status: epileptic (136M, 80F: EEG with spike;47M, 40F without); clinical status: nonepileptic: (98M, 65F EEG with spike; 68M, 49F without). Numerical data were acquired with EEG dump diagnostic Biologic system at Sarjito hospital Yogyakarta etc, 20022011. The wave components were sorted out according to their amplitudes, time span between zerocrossings, and different frequencies wavelet. Result: The experimental results the spikes show consistent large outputs throughout the wavelet set, they have sharpness at several different resolutions. Utilizing the hardware and software facilities at hand, marking the starts and ends of abnormal waves could be done with +100 lV threshold. The zerocrossings and crosscorelation detection could automatically distinguished according to the 2070 ms time period for the spikes (89M, 58F),70120 ms for sharps (160M, 101F), and the existence of multiple peaks for polyphase(100M,75F). Conclusion: The research carried out so far was to find the prospect of this digital signal processing on EEG waves to support the doctors work in this field.
p300 PGES IS MORE FREQUENT IN CONVULSIVE SEIZURES ARISING FROM SLEEP R. J. Lamberts*, S. Laranjo, S. Kalitzin*, D. Velis*, I. Rocha, J. W. Sander*, and R. D. Thijs
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p302 REFLEX MYOCLONIC EPILEPSY IN INFANCY: A MULTICENTER CLINICAL STUDY S. Matricardi*, A. Verrotti*, G. Capovilla, C. DEgidio*, R. Cusmai, A. Romeo, D. Pruna, P. Pavone**, S. Cappanera, T. Granata, G. Gobbi, P. Striano, S. Grosso***, P. Parisi, E. Franzoni, S. Striano, A. Spalice, R. Marino*, F. Vigevano, and G. Coppola *University of Chieti, Chieti, Italy; C. Poma Hospital of Mantova, Mantova, Italy; Bambino Ges Children's Hospital of Rome, Rome, Italy; Fatebenefratelli e Oftalmico Hospital of Milan, Milan, Italy; Azienda Ospedaliero Universitaria of Cagliari, Cagliari, Italy; **University of Catania, Catania, Italy; Ospedali Riuniti of Ancona, Ancona, Italy; IRCCS Foundation Neurological Institute C. Besta of Milan, Milan, Italy; Maggiore Hospital of Bologna, Bologna, Italy; Gaslini Institute, University of Genova, Genova, Italy; ***University of Siena, Siena, Italy; La Sapienza University of Rome, Rome, Italy; University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy; Federico II University of Napoli, Napoli, Italy; and University of Salerno, Salerno, Italy
Purpose: Reflex myoclonic epilepsy in infancy (RMEI) is a rare clinical entity and most of the available evidence (Ricci S et al. Epilepsia 1995;36:342348; Giovanardi Rossi P et al. Brain Dev 1997;19:473 479; Caraballo R et al. Rev Neurol 2003;36:429432), based on anecdoctal cases, are inconclusive regarding its evolution and prognosis. We describe the clinical and electroencephalographic (EEG) features and long-term cognitive outcome. Method: We enrolled 31 children from 16 neuropediatric centers in Italy, who underwent periodical clinical and video-EEG evaluation. Cognitive assessment was performed in all patients using standardized psychometric tests according to their age. Result: The age at onset ranged from 3 to 24 months of age. Seizures were characterised in all patients by symmetric myoclonic seizures (MS), triggered by sudden unexpected acoustic (38.7%) or tactile stimuli (29%) or both (29%). Photosensitivity was absent in all patients. Spontaneous attacks were reported in 32.2% of the cases. Interictal EEG was normal in all cases. Ictal EEG showed generalized high-amplitude 3 Hz polyspike and wave discharges, synchronous with brief rhythmic bursts of electromyographic activity . Patients were re-evaluated after a period of 7.2 5.6 years. The prognosis for seizure control was excellent in all cases and reflex MS disappeared spontaneously or after valproate treatment. The cognitive outcome was excellent in 90.3% of children. Conclusion: RMEI appears to be a variety of idiopathic generalized epilepsy with specific features that occurs in developmentally normal children, which should be classified as a distinct nosographic syndrome. Purpose: The conventional research method to screen for epilepsy is with a written questionnaire administered door-to-door (WQ). Although this enables comprehensive capture of undiagnosed and untreated cases, it is resource intense, insensitive to non-convulsive seizures and inefficient for large-scale recruitment for aetiologic or prognostic studies. Our aim was to field test a novel digital animation seizure-screening questionnaire that may be more suitable for community-based recruitment. Method: We developed a series of high-resolution digital animations depicting visual sequences of young people with seizures (AQ) consisting of: tonic-clonic, simple partial motor, complex partial temporal lobe, absence and myoclonic. We administered AQ to parents of primary and secondary school students and secondary school students by a specially constructed website www.sparks.org.au. All students underwent epilepsy specialist assessment (ESA) including EEG when indicated, to confirm the diagnosis of epilepsy. AQ was repeated after first completion, to estimate repeatability. Result: 206 AQ internet surveys were conducted (157 parental, 38 students) with all undergoing ESA: 8 screened positive with 3 confirmed cases of epileptic seizures, 2 of which were new. Both parental and student's surveys combined: sensitivity 1.00 (1.001.00), specificity 0.95 (0.920.99), Youden's Index a summary measure of sensitivity and specificity 0.95 (0.930.99). Surveying only parents improved specificity slightly without affecting sensitivity. Repeat survey (n = 62) demonstrated 100% concordance. Conclusion: Although numbers are relatively small, early results suggest that AQ may be a more effective population-screening instrument than WQ. In addition, it should greatly improve efficiency as it can readily recruit individuals and households through devices that access the internet rather than door-to-door.
p304 AN COMPETENCY FRAMEWORK FOR ADULT EPILEPSY SPECIALIST NURSES Y. Leavy*, M. Goodwin, S. Higgins, and V. Myson *Western General Hospital, Edinburgh, UK; Northampton General Hospital, Nothampton, UK; Glocestershire Royal Hospital, Gloucester, UK; and Cardiff and Vale NHS trust, Cardiff, UK
Purpose: Epilepsy affects approximately 600,000 people in the UK (UK) (Joint Epilepsy Council 2011). For over twenty years adult Epilepsy Specialist Nurses (ESNs) have been managing epilepsy and supporting people with epilepsy (PWE). However, despite this long association there are currently no guidelines for employers or stakeholders regarding the entry experience or qualifications when recruiting an adult ESN. The adult ESN competency framework attempts to address this. It also defines core competencies thought to be central to effective performance and attempts to articulate progression from a novice specialist nurse through to competent and ultimately expert specialist nurse. In practice this framework should provide practical and aspirational guidance for ESN's and for those involved in assessing their competence to practice. Method: The Adult ESN Competency Framework has been developed by a UK-wide steering group of ESNs with a variety of experience, and reviewed by academics, and researchers. Literature reviews of relevant healthcare policy, nurse training and epilepsy guidelines were undertaken. This work has been led by the Epilepsy Nurses Association (ESNA) and accredited by the Royal College of Nursing (RCN), with the support of Epilepsy Action to provide a patient perspective. Result: The competency framework consists of nine dimensions: A Knowledge of Epilepsy B Clinical Management of Epilepsy C Independent Living D Joint Working/Professional Relationships E Personal Planning and Organisation F Teaching Patients G Audit H Research I Epilepsy Surgical Management/VNS.

p303 A NOVEL INTERNET ANIMATION SEIZURE SURVEY MAY BE AN EFFECTIVE SCREENING INSTRUMENT FOR POPULATION-BASED RESEARCH W. J. DSouza, J. Freeman, S. Harvey, and M. Cook The University of Melbourne, Melbourne, Vic., Australia
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Conclusion: The adult ESN competency framework provides practical and aspirational guidance for ESN's and employers regarding entry and ongoing qualifications, experience and clinical competence. word shorthand diary Gowers kept when apprenticed to a country doctor in Essex in 18623. These discoveries have enabled the authors to offer a fuller account of Gowers early professional development and later interests, the social context within which he functioned, and his contributions to the expanding neurological understanding of his day. Conclusion: This new biography brings to a wide readership the life and work of a great medical neurologist, offering additional insights on Victorian medicine more generally; and it makes available a rich store of archival material never previously published.
p305 TREATMENT GAP OF EPILEPSY IN PAKISTAN: A POPULATION-BASED STUDY Z. Mogal, S. W. Akhtar, R. Malik, and H. Aziz National Epilepsy Centre, Jinnah Postgraduate Medical Centre, Karachi, Pakistan
Purpose: To assess any change in treatment gap status of epilepsy in Pakistan following a countrywide intensive and sustained epilepsy awareness program. Background: According to the population-based epidemiologic and knowledge, attitude and practice study of 1987, prevalence of epilepsy in Pakistan was 0.98% with a treatment gap of 86%; lack of knowledge and wrong cultural beliefs about the condition being main reasons (Aziz H et al. Epilepsia 1994;35(5):950958). Intensive and sustained countrywide epilepsy awareness through Comprehensive Epilepsy Control Programme of Pakistan is ongoing since 2001. Five years after initiation of this public awareness campaign, another population-based study was performed and treatment gap status re-assessed. We are presenting part results of this study. Method: A door-to-door population-based epidemiologic study was conducted in urban and rural areas of Sialkot in northern Pakistan. Sample collection was done by random block selection method in proportion to the population structure of the area. Questionnaire based on ICBERG protocol (same as used in 198589 study) was applied. Result: Of the 3780 people screened from 762 households, 55 (1.46%) had epilepsy. Of the 53 people with epilepsy (data on 2 is unsubstantiated), 30 (56.6%) were taking atleast one antiepileptic drug whilst 23 (43.4%) were not taking any medications at the time of survey. Conclusion: Treatment gap of epilepsy in Pakistan has decreased from 86% to 43.4% after five years of intensive epilepsy awareness campaign, countrywide. With all other variables remaining constant, an intensive and sustained public awareness campaign has been instrumental in decreasing the treatment gap.
p307 TROPONIN LEVELS AFTER SEIZURES AND RELATIONSHIP TO CARDIOVASCULAR RISK FACTORS A. Fawaz*, W. Nasreddine, S. Atweh*, J. Wazneh*, A. Rabah*, M. Arabi*, and A. Beydoun* *American Unveristy of Beirut, 2020, Lebanon; and Rafic Hariri University Hospital, Beirut, Lebanon, Beirut, Lebanon
Purpose: Troponin is a very sensitive marker of cardiac injury. Conflicting data regarding elevation of troponin level following generalized tonic clonic seizures (GTCs) have been reported. In this study we hypothesized that troponin elevation after GTCs occurs more frequently in patients with cardiovascular risk factors. Method: Consecutive patients who presented to ER over a one year period with a GTC and whose work up included troponin T level were included. Patients with cardiac symptoms at the time of admission or renal insufficiency were excluded. The frequency and risk factors for elevated troponin levels in this cohort were analyzed. Result: Fourteen patients (mean age: 54 years; range: 1987) were included. Four patients (28.6%) had an elevated troponin level (Mean = 0.06, range: 0.0350.076). Those four patients were significantly older than those with normal levels (77.5 vs. 45.5 years, P = 0.035). EKGs in these patients were normal. Of the eight patients 60 years or older, four (50%) had an elevated troponin level. The coronary heart disease score (CHD) was significantly higher in patients with high troponin compared to those with normal troponin levels (13.5 vs. 9.75, P = 0.012). Conclusion: Elevated troponin levels can occur after a GTC. The significantly higher frequency in the elderly and in patients with high CHD scores strongly suggests that this increase is mostly due to cardiac injury.
p306 WILLIAM RICHARD GOWERS 18451915: EXPLORING THE VICTORIAN BRAIN A. Scott The University of Queensland, Brisbane, Australia
Purpose: The Victorian neurologist William Richard Gowers was a clinician, researcher, writer, and teacher, whose prolific output included the two-volume Manual of Diseases of the Nervous System (1886 and1888), and numerous publications on epilepsy, culminating in The Borderland of Epilepsy (1907) (which introduced this term into the medical literature). In 1949 Macdonald Critchley wrote a biographical appreciation of Gowers in which he referred to the peculiar dificulties in gathering objective material about a man admired but not understood. Method: This more comphrehensive biography, to be published in 2012 by Oxford University Press, is by Professor Ann Scott (Gowers greatgranddaughter), and neurologists Professors Mervyn Eadie and Andrew Lees. The aim of the authors has been to draw on newly-available resources to re-examine Gowers life and his contributions to neurological science. Result: The authors uncovered important new primary sources from the Gowers family papers and other archives, including significant finds at the National Hospital, Queen Square. Scott also transcribed the 83,000Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x
p308 OCCURRENCE OF ICTAL ARRHYTHMIA IS ASSOCIATED WITH A FIRST-DEGREE FAMILY HISTORY OF EPILEPSY G. O Connor, A. O Donnell, G. Mullins, E. Chaila, and N. Delanty Beaumont Hospital, Dublin, Ireland
Purpose: Seizure-induced disturbances in cardiac rhythm (known as ictal arrhythmias) are well recognised phenomena, the causes of which are unclear. To explore a possible genetic basis for this phenomenon, we sought to quantify the strength of association of ictal arrhythmia with a first-degree family history of epilepsy. Method: We identified all patients admitted to the Epilepsy Monitoring Unit in our centre between January 2005 and August 2011. For inclusion, patients had to have had definite epileptic events during the period of monitoring, and to have their details recorded on our epilepsy-specific electronic patient record. For all patients included, we recorded demographic details, family history of epilepsy, imaging findings and EEG findings, and we recorded the occurrence or not of any ictal arrhythmia. For all the specified features, we calculated the significance of the association between them and the occurrence of ictal arrhythmia.
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Result: A total of 224 patients met the criteria for inclusion. Of these, 13 patients (5.8%) had an ictal arrhythmia other than sinus tachycardia. A first-degree family history of epilepsy was found to be associated with the occurrence of ictal arrhythmia (p = 0.0067). There was no statistically significant association for any of the other features studied, including hemisphere of seizure onset, extratemporal seizure focus or imaging findings. Conclusion: The association of ictal arrhythmia with a first-degree family history of epilepsy has not been demonstrated previously, and suggests an underlying genetic basis for this phenomenon. Further research into the underlying genetic mechanism of ictal arrhythmia is warranted. radiation therapy and chemotherapy at age 1 year. Her complex partial seizure started at age 19 years. She was treated with various medications including valproate (VPA) (as monotherapy for 1 year) without effects nor relevant side effects. We gave her LTG up to 200 mg/day without seizure control. We added VPA 200 mg/day, then she became seizure free. Shortly after addition of VPA, normocytic normochromic anemia emerged and rapidly progressed to reticulocyte count 0&. Leukocytopenia and thrombocytopenia were not observed. Drug-induced acute PRCA was suspected and VPA was discontinued, but anemia still progressed to hemoglobin (Hb) 5.7 g/ml. Transfusion of two units of packed red cells was needed. As reticulocyte count still remained 1& on 20th day after cessation of VPA, LTG was discontinued. Soon after discontinuation of LTG, reticulocyte count increased dramatically up to 116&, and subsequently anemia improved. Two months after discontinuation of LTG, RBC and Hb were normalized. Conclusion: To our knowledge, this is the second case report of PRCA following LTG treatment in a patient without known hematological disorder. Monitoring blood count is highly recommended after initiation of LTG treatment.
p309 ASSOCIATION BETWEEN EPILEPSY AND CYSTICERCOSIS AND TOXOCARIASIS: A POPULATION-BASED CASECONTROL STUDY IN AN URBAN SLUM IN INDIA G. Singh, J. Bawa, D. Chinna, A. Chaudhary, K. Saggar, M. Modi, and J. W. Sander Dayanand Medical College and Hospital, Ludhiana, India
Purpose: To study the association between epilepsy and exposure to the parasites, Toxocara canis and Taenia solium. Method: A door-to-door community-based survey of epilepsy was carried out in an urban slum area with a population of 15,750. People with active epilepsy were subjected to detailed epileptological assessments, sleep and awake EEGs and high-strength (1.5 Tesla) epilepsy protocol magnetic resonance imaging. For every case, one age- and gendermatched control was selected from the same community. Serological evaluation was carried out for both cases and controls to detect antibodies against T. canis and T. solium. Result: The crude prevalence of active epilepsy was 7.2/1000. 114 people with confirmed active epilepsy (45 females; 69 males) and 114 controls were enrolled. The prevalence of antibodies to T. canis was similar in people with active epilepsy (4.4%, 5 of 114 people) and in controls (6.1%, 7 of 114 people). The prevalence of antibodies to T. solium was 23.7% (27 out of 114 cases) in people with active epilepsy, which was significantly higher than the prevalence in controls (13 out of 114 cases; 11.4%) (P = 0.02). After adjusting for potential confounding factors, conditional (fixed-effects) logistic regression provided an odds ratio of 2.55 (95% CI, 1.14 to 6.28). Nineteen people with active epilepsy demonstrated evidence of neurocysticercosis on MRI, (solitary cysticercus granuloma 7, solitary calcification 7 and multiple mixed stages 5). Conclusion: Although significant association between T. solium exposure and epilepsy was observed but no such association was seen between T. canis and epilepsy.
p311 THE ROLE OF MINOCYCLINE ON DEVELOPMENT OF AMYGDALA KINDLING IN WISTAR RATS S. M. Beheshti Nasr, and M. Mohammad-Zadeh Sabzevar University of Medical Sciences, Sabzevar, Iran
Purpose: Minocycline is a derivative of tetracycline that has antiinflammatory, antiappoptic and antioxidant properties. Minocycline readily crosses the blood brain barrier and attenuates inflammation, it also affect on neural cell activity. For example it has been shown minocycline inhibit microglia activation and reduce astrocytic reactivation addition it has neuroprotective effects. As far as there is interaction between cell death and seizure, the aim of this study is examination of the role of minocycline on amygdala kindled seizures in rat. Method: In this experimental study, three group animals (21 rats), after sterotaxic surgery and 1 week recovery period, rats received kindling stimulations (twice daily at 6 hour interval). Group 1(n = 7) animals received daily kindling stimulations. Group 2 (n = 7) and 3(n = 7) 60 min before kindling stimulation received saline (1 ml/kg) and minocycline (25 mg/kg) respectively. Cumulative Afterdischarge duration (ADD), Cumulative Seizure duration (SD) and Seizure Stage (SS) were recorded and compared relative to control group. Data analyzed with Statistica software (Ver 5.5). Repeated measure ANOVA and Post hoc tukey test for comparison within groups and student's t-test was used for comparing two groups of data. A P-value of less than 0.05 was considered to represent a significant difference. Result: In group 3 intraperitoneal administration of minocycline for 10 days reduced cumulative ADD [F(18, 216)=3.5, p < 0.001] and cumulative SD [F(19, 228)=3.8, p < 0.001] significantly relative to control group (group 2). It also significantly increased the mean number of stimulations to achieve to seizure stages of 3 (P < 0.05), and 5 (P < 0.001). Conclusion: According to obtained results it may be concluded that application of minocycline have anticonvulsant effect on kindling model of epilepsy.
p310 ACUTE PURE RED CELL APLASIA. RARE COMPLICATION OF LAMOTRIGINE TREATMENT H. Ikeda, H. Ikeda, and Y. Inoue National Epilepsy Centre, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan
Purpose: To report that pure red cell aplasia (PRCA) can occur as a rare side effect of lamotrigine (LTG). Method: We report a patient presenting with acute PRCA following LTG treatment. Result: Patient is a 25 year-old female with focal epilepsy and mental retardation. She has a history of surgery for cerebellar tumor, subsequent
p312 DIFFERENT TYPES OF HEADACHE IN PATIENTS WITH EPILEPSY CLINICAL INVESTIGATIONS C. Lorenzen, M. Prieschl, M. Bergmann, G. Walser, C. Gneis, I. Unterberger, and G. Luef Medical University Innsbruck, Innsbruck, Austria
Purpose: Epilepsy is known to be associated with different comorbidities in particular headache. The aim of our study was to examine the
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distribution of different headache types in patients with epilepsy. We tried to determine whether migraine is the most common headache type in epilepsy and if antiepileptic drugs are useful for headache prophylaxis. Method: In this single-centre study we consecutively investigated patients with epilepsy using a validated self-administered headache questionnaire for screening for migraine (MIG), tension-type headache (TTH), and trigeminal-autonomic cephalgias (TAC). Additionally we asked for onset and type of epilepsy, seizure associated headache, antiepileptic drug treatment and their influence on headache followed by a question regarding seizure frequency. Result: Five hundred epileptic patients with equivalent sex distribution and a mean age of 45.52 years (+-17,26) were enrolled. One hundred sixty three patients, 43.2% female and 22.0% male, reported to suffer from headache. Migraine was the most frequent type in general (41.7%), and in women (47,2%), TTH in male (41,8%). Antiepileptic drug treatment was used by 158 patients, sixty (38.0%) reported to have a reduction in frequency of headache. With regard to the different headache types, levetiracetam reduced frequency of headache best (50.0%), followed by valproic acid (41.2%) and lamotigine (26,3%). Conclusion: Three different headache types are present in epilepsy patients. A short questionnaire seems to be helpful in diagnosing headache. AED treatment improved headache and polypharmacy. Levetiracetam followed by Valproat was shown to have the best influence on headaches in general.
p314 A COMPARISON STUDY OF THE QUALITY OF LIFE (QOL) IN EPILEPSY, MS, AND HEALTHY CONTROLS IN SAUDI ARABIA H. Alkhamees, and C. Selai UCL, London, UK
Purpose: This study was conducted to compare (QOL) in patients with epilepsy, patients with MS and healthy controls from Saudi population. Method: The QOL of (110) patients with epilepsy, (114) patients with MS, and (136) healthy controls all from Saudi Arabia was assessed using two scales (QOLIE-31 and the RAND SF-36). Translation and validation of the QOLI-31 from English to Arabic was done. Result: A comparison between the three groups QOL will be presented as preliminary results. Conclusion: Preliminary results show the QOL within the three groups.

p313 PSYCHOSOCIAL OUTCOME AND PATIENT SATISFACTION 10 YEARS AFTER TEMPORAL LOBE RESECTION FOR EPILEPSY L. Andersson-Roswall, E. Engman, H. Samuelsson, and K. Malmgren Institute of Neuroscience and Physiology, Gothenburg, Sweden
Purpose: Knowledge about long-term psychosocial outcome of temporal lobe resection (TLR) for epilepsy is limited. The aim of this study was to explore long-term psychosocial outcomes and patient satisfaction with TLR and to investigate the relationship between long-term vocational and memory outcomes. Method: A cohort of 51 patients was prospectively followed 10 years after TLR. Psychosocial and neuropsychological data was prospectively ascertained at baseline and 10 years after surgery and at corresponding time-points for 23 controls. 40/51 patients (78%) also answered two surveys at long-term follow-up including the Hospital Anxiety and Depression Scale (HAD), a global quality of life (QOL) assessment and questions on patient satisfaction with surgery. Result: Fewer patients worked 10 years postoperatively (TLR: 61%; controls: 96%; p = 0.002) compared to baseline (TLR: 73%; controls: 83%; NS). The odds of working full time 10 years after surgery were 9.5 times higher with seizure freedom (p = 0.022). There were no associations between working at 10 years and side of resection and verbal memory outcome. Most patients scored low on HAD indicating few emotional problems. Seizure-free patients were more satisfied with surgery (p = 0.027), experienced less disadvantages of their TLR (p = 0.022), and had a better QOL (p = 0.014). Conclusions: In this study TLR did not lead to better vocational outcome. However, seizure-free patients were more likely to work full-time 10 years postoperatively and verbal memory impairment did not have an influence on vocational outcome. Patients were in general satisfied with epilepsy surgery, those seizure-free more than those with seizures.
p315 EPILEPTIC ENCEPHALOPATHIES OF THE LANDAUKLEFFNER AND CONTINUOUS SPIKE AND WAVES DURING SLOW-WAVE SLEEP TYPES: GENOMIC DISSECTION MAKES THE LINK WITH AUTISM G. Lesca*, G. Rudolf, A. Labalme, E. Hirsch, A. Arzimanoglou*, P. Genton, J. Motte, A. De Saint Martin**, M. Valenti**, C. Boulay**, J. De Bellescize, P. Keo-Kosal, N. Boutry-Kryza, P. Edery*, D. Sanlaville*, and P. Szepetowski *CRNL, CNRS UMR 5292, INSERM U1028, Lyon, France; Strasbourg University Hospital, Strasbourg, France; University Hospital of Lyon, Bron, France; Henri Gastaut Hospital, Marseille; American Memorial Hospital, Reims University Hospital, Reims, France; **Strasbourg University Hospital, Strasbourg; Epilepsy, Sleep and Pediatric Neurophysiology Dpt, Lyon, France; Lyon University Hospital, Claude Bernar University Lyon 1, Lyon; and Mediterranean Institute of Neurobiology (INMED), Marseille,
Purpose: The continuous spike and waves during slow-wave sleep syndrome (CSWSS) and the Landau-Kleffner (LKS) syndrome are two rare epileptic encephalopathies sharing common clinical features including seizures and regression. Both CSWSS and LKS can be associated with the EEG pattern of electrical status epilepticus during slow-wave sleep and are part of a clinical continuum that at its benign end includes Rolandic epilepsy (RE) with centro-temporal spikes. Patients can also have behavioral manifestations that overlap the spectrum of autism disorders (ASD). An impairment of brain development with complex interplay between genetic and non-genetic factors has been suspected but the pathophysiology of CSWSS and of LKS remains unknown. In the recent years, the participation of rare copy number variations (CNVs) in the susceptibility to various brain diseases including epileptic and autistic disorders has been demonstrated. Method: The involvement of rare CNVs in 61 CSWSS and LKS patients was questioned using comparative genomic hybridization assays (4 180 Agilent microarrays). Result: Whereas the patients showed highly heterogeneous in genomic architecture, several potentially pathogenic alterations were detected. Many of these corresponded to genomic regions or genes that have been associated with either ASD, or speech or language impairment, or RE. Particularly, CNVs encoding cell adhesion proteins were detected with high frequency.
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Conclusion: Overall our data bring the first insights into the possible molecular pathophysiology of CSWSS and LKS. The detection of cell adhesion genes and the strong overlap with the genetic and genomic ASD networks, provide an exciting and unifying view on the clinical links between CSWSS, LKS and ASD. characterized by desynchronization of basic EEG-rhythm. The most important diagnostic criteria for epileptic patients are dynamic characteristics of the DV: elongation, increased appearance of negative emotions. Conclusion: There was allocated of two types of deja-vu: pathological-epileptic, characteristic of patients with epilepsy and equivalent to an epileptic seizure, nonpathological-nonepileptic deja-vu, which is characterized for healthy people.
p316 SEIZURE SEMIOLOGY OF A HOT WATER SEIZURE CASE O. Karadas*, I. Ipekdal, and H. L. Gul *Erzincan Military Hospital, Erzincan, Turkey; Marasal Cakmak Hospital, Erzurum, Turkey; and Kartal Education and Research Hospital, Istanbul, Turkey
Purpose: Hot water epilepsy (HWE) or bathing epilepsy is the group of reflex epilepsies. It is induced by hot water pouring over the head, face, neck, or trunk during bathing. The aim of this study was to demonstrate the seizure semiology by following up the seizure with all the changes that occured before, during and after the seizure. Method: An informed consent form was signed by the patient and the needed precautions were taken. Under the supervision of a doctor and a nurse; the patient's seizure was induced by having a bath with 40C hot water. Each step of the semiology was recorded by a neurologist. Result: 1,5 minutes after starting to bath, the patient's breathing became deeper and a fearful facial expression had developed. This status had continued for 510 seconds, then a pause in the speech and pupillary dilatation was detected. 5 seconds after this status, the patient became unconscious with oral automatisms and the deviation of the head and eyes to the right. At this state, intervention was made and while taking the patient out of the bath, he had a 68 seconds of generalised tonic seizure followed by a 20 seconds of generalised clonic seizure. His postictal confusion continued for 10 minutes and after that period, his neurological examination had turned to normal. Conclusion: This case is important for; the determination of the seizure semiology of hot water epilepsy as a reflex epilepsy and the comparison of hot water epilepsy with the other epilepsies.
p318 TRANSIENT EPILEPTIC AMNESIA: DESCRIPTION OF TWO CASES S. Meregalli, and M. Brioschi A. O. Niguarda C Granda, Milano, Italy
Purpose: Case reports over the past 100 years have raised the possibility that epilepsy can manifest itself in episodes of amnesia. Transient Epileptic Amnesia (TEA) is a relatively recently characterized syndrome of temporal lobe epilepsy. Method: Transient Epileptic Amnesia (TEA) is a distinctive syndrome of temporal lobe epilepsy principally affecting middle-aged people, giving rise to recurrent, brief attacks of amnesia, often occurring on waking. It is associated with a form of persistent interictal memory impairment, i.e. accelerated long-term forgetting and remote memory impairment. The syndrome is of clinical importance, as the amnesic episodes are often misdiagnosed initially but respond promptly to antiepileptic drugs. The diagnostic criteria for TEA are as follows: 1) A history of recurrent witnessed episodes of transient amnesia. 2) Cognitive functions other than memory judged to be intact during typical episodes by reliable witness 3) Evidence for a diagnosis of epilepsy based on one or more of the following: (a) epileptiform abnormalities on electroencephalography (b) the concurrent onset of other clinical features of epilepsy (c) a clear-cut response to antiepileptc drugs. We describe two new cases of TEA, filling these diagnostic criteria. Result: WE describe two middle-aged womans, with episodes of TEA, promptly responding to antiepileptic drugs-therapy. Conclusion: Transient Epileptic Amnesia is an under-recognized but treatable cause of transient memory impairment. It is important to make a differential diagnosis with other forms of transient impairment of memory, like Transient Global Amnesia etc.
p317 DEREALIZATION DISORDERS IN EPILEPSY P. Vlasov*, and A. Chervyakov *Moscow State Medical and Stomatology University, Moscow, Russian Federation; and Research Center of Neurology RAMS, Moscow, Russian Federation
Purpose: To examine the clinical and diagnostic value of derealization disorders in epilepsy. Deja vu (DV) phenomenon is the most common and recognizable derealization disorder. Method: Study group of 166 persons (average age 25,2 9,2; 63,2% of women). Derealization was compared in two groups: I healthy people (n = 139), II patients with epilepsy (n = 27). Provided that healthy respondents have never had any of the paroxysmal manifestations. Longtime EEG monitoring was performed for all patients of the second group and for 5 healthy participants with frequent DV. We used our own unique questionnaire. Result: For patients with epilepsy DV phenomenon occurs in cryptogenic and symptomatic focal epilepsy, it can be combined with virtually all types of seizures, could be aura of a seizure, and self-attack. For the first time there was recorded EEG-pattern of DV phenomenon in epilepsy, that is characterized by the beginning of spike activity in the right temporal lobe and, in some cases (longer duration of phenomenon), ended in slow wave, theta-delta activity in the right hemisphere. In one healthy volunteer the EEG-pattern of DV-phenomenon was
p319 EPILEPTC APHASIA: A DESCRIPTION OF 10 NEW CASES A. Lpez-Ferreiro*, X. Rodrguez-Osorio*, J. C. FernndezFerro, T. Garca-Sobrino*, M. Rodrguez-Yaez*, M. Arias*, J. Pardo*, E. Corredera*, and F. J. Lpez-Gonzlez* *Complejo Hospital Clnico Universitario de Santiago de Compostela, Santiago de Compostela, Spain; and Hospital Infanta Elena, Madrid
Purpose: Recurrent or prolonged aphasia as sole clinical manifestation of epilepsy is a rarely described phenomenon. We aim to describe the epileptic aphasias diagnosed in our hospital. Method: We considered ictal aphasia as language production with aphasic features in conscious patients. Episodes were classified as status epilepticus or simple partial seizures according to ILAE guidelines, and may present as Broca, Wernicke or mixed aphasia. Diagnosis was based on clinical features plus EEG findings or clear response to antiepileptic drugs (AED), with exclusion of acute structural aetiologies on MRI. We
94 Abstracts
analyzed demographic, clinical and EEG characteristics, response to treatment and follow-up. Result: Ten women (100%), with a mean age of 66.6 years old were included (4985) Two had previous history of epilepsy. Mixed aphasia occurred in 5 patients, Broca in four and Wernicke in one. In 9 cases an ictal EEG was obtained: 4 demonstrated left regional epileptiform activity and other 4, left hemisphere slowing. Six patients presented with status epilepticus and four with simple partial seizures. One patient showed transitory edema in the MRI. Benzodiazepines were used as first-line AED in 6 patients, with clinical response in 4, EEG response in 1 and both in 1. All patients clinically recovered with AEDs (LEV 70%). In the follow-up, 7 cases achieved an excellent control and three recurred. Conclusion: Diagnosis of epileptic aphasia is challenging. An epileptic aetiology should be considered in the differential diagnosis of episodic speech errors. Ictal EEG findings and response to AEDs are useful in the diagnosis and management of these patients. Purpose: To elucidate features of the seizure semiology in children with protocadherin 19-related epileptic encephalopathy (PCDH19EE), because of lack of detailed description regarding seizure manifestation based on video-EEG recordings in the literature. Method: We analyzed ictal video-EEG recordings of 26 seizures in three girls with PCDH19EE. Result: The sequence of seizure manifestation was very similar among all three patients, consisting of five common segments, which we named Jerk, Reactive, Mild tonic, Fluttering and Post-ictal/Oral automatism. Some segments are brief or lacking, while others are long or pronounced. Reactive, Mild tonic and Fluttering segments are more characteristic. In Reactive, the patients seemed so startled by sudden Jerk that they reactively turned over. Tonicity in Mild tonic was less intense than that of tonic-clonic seizures of other epilepsies. Fluttering was characterized initially by asymmetric, less rhythmic, less synchronous tremulous movement and later by subtle clonic movement. There was subtle oral automatism in the postictal phase. Seizure lasted from a few to sixty seconds. All seizures occurred in clusters associated with high fever. Ictal EEGs started initially bilateral in some, but asymmetric at the very onset in some others, and later showed apparent asymmetric rhythmic discharges. Conclusion: Seizures have more or less asymmetric focal features in the electro-clinical aspects. Characteristic seizure sequence in PCDH19EE was so unique that its occurrence in clusters associated with high fever in girls would readily suggest PCDH19EE.
p320 SEMIOLOGIC AND EEG FEATURES OF PATIENTS WITH TEMPORAL LOBE EPILEPSY AND HIPPOCAMPAL SCLEROSIS WHO WERE SEIZURE-FREE FOLLOWING SURGERY lu Toydemir*, C. zkara, and M. Uzan H. Ertas og *S is li Etfal Research and Education Hospital, Istanbul, Turkey; Istanbul University School of Medicine, Istanbul, Turkey; and _ Istanbul University Cerrahpas a Medical Faculty, Istanbul, Turkey
Purpose: Despite the high rate of favorable outcome after standardized surgery, 2030% of patients with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS) still continue to experience seizures. The aim of this study is to determine whether there is evident semiologic and EEG features which may predict the seizure freedom after surgery. Method: Semiologic and EEG findings of 126 ictal video-EEG recordings corresponding to 50 patients who stayed seizure free for at least 3 years (mean: 9.46 3.20; range: 314.5 years) after surgery were reviewed. About 94% of them have already discontinued drugs. Result: Aura was reported in 82% (n:41) of the patients. Epigastric sensation was the most common aura. Early symptoms (within the first 30 seconds) were contralateral arm dystonia (%60), ipsilateral hand automatisms (%54) and oro-alimentary automatisms (%48). Two or three of these symptoms were seen together in %56 of the patients without any unique sequence. Ictal EEG findings revealed localized and lateralized activity in 66% of them. Conclusion: The presence of three semiological features during the early ictal period and localized and lateralized ictal EEG activity seem to be common features in this highly selected patient population. Although, other types of semiologic and EEG findings detected besides them suggest a more extended epileptogenic zone, the fact that they benefit from the same surgical procedure may be associated with the critical role of resected area in both the generation and propagation of the seizure activity.

p322 RELIABILITY OF POSTICTAL NOSE RUBBING FOR LOCALIZATION AND LATERALIZATION OF EPILEPTOGENIC ZONE IN FOCAL EPILEPSIES N. M. Vojvodic*, A. J. Ristic*, L. M. Popovic, V. L. Bascarevic, D. V. Sokic*, A. Parojcic*, S. M. Jankovic*, M. M. Kovacevic*, L. Brajkovic, and B. Djurovic *Neurology Clinic, Belgrade, Serbia; St Sava Hospital, Belgrade, Serbia; Clinic of Neurosurgery, Clinical Center of Serbia, University of Belgrade, School of Medicine, Belgrade, Serbia; and Institute of Nuclear Medicine, Belgrade, Serbia
Purpose: To evaluate the usefulness of postical nose rubbing (PNR) as the localization and lateralization sign in focal farmacoresistant epilepsies. Method: Retrospectively, we analyzed seizure semiology in 266 patients with focal farmacoresistant epilepsy. All patients were undergone five day noninvasive video-EEG monitoring in our telemetry unit and brain MRI according to the presurgical protocol. In 162 patients we were able to establish the lobar diagnosis. In all patients we analyzed clinical seizure semiology in order to determine the occurrence of PNR in temporal lobe epilepsies (TLE) vs. extratemporal lobe epilepsies (ETLE), and it's lateralizing value (ipislateral or contralateral to the epileptogenic zone) when perform exclusively with one hand. Result: We found PNR in 40 out of 106 patients with TLE and in 7 out of 56 patients with ETLE (37,7% vs. 12,5%, p = 0.001). In 27 (57,4%) patients, PNR was performed always with hand ipsilateral to the epileptogenic zone, in 11 (23,4%) patients with contralateral hand and in 9 (5,2%) patients with both hands (p = 0.008).
p321 CHARACTERISTIC SEIZURE SEMIOLOGY IN PCDH19-RELATED INFANTILE EPILEPTIC ENCEPHALOPATHY H. Ikeda, K. Imai, H. Ikeda, R. Takayama, H. Ohtani, H. Shigematsu, Y. Takahashi, and Y. Inoue National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan
95 Abstracts
Conclusion: We found PNR was reliable localizing sign for TLE and when performed exclusively with one hand, it was significantly more common with ipsilateral hand to the epileptogenic zone. has been seizure-free for a long period since he developed Status Epilepticus followed by Refractory SE, than Super Refractory SE occurred. EEG and MRI changes occurred during his follow-up: serial MRI examinations showed progressive cortical laminar necrosis while EEG recordings showed paroxysmal epileptiform discharges. Suppression burst never appeared after anesthetic therapy. These findings suggest an ongoing neuronal injury that currently persists after 5 months of SE despite all treatments. Result: These findings suggest an ongoing neuronal injury that currently persists after 5 months of SE despite all treatments. Conclusion: Morbidity and mortality in Super Refractory SE is very high. The outcome depends on the underlying etiology but, in our patient, no cause was found until now.
Basic Science 5 Tuesday, 02 October 2012

p323 THE OUTCOME OF THERAPIES IN REFRACTORY AND SUPER-REFRACTORY CONVULSIVE STATUS EPILEPTICUS AND RECOMMENDATIONS FOR THERAPY M. Ferlisi, and S. Shorvon National Hospital for Neurology & Neurosurgery, London, UK
Purpose: The purpose of this report is to provide a comprehensive analysis and synthesis, from the published literature from 1981, of the outcome of therapies used in refractory or super-refractory status epilepticus, and to provide recommendations about a treatment protocol. Method: We analysed all 141 papers reporting outcome of 1168 patients with refractory and super-refractory status epilepticus, treated with various therapies. Result: Control of refractory and super-refractory status epilepticus was reported in 74% of the cases treated with anaesthetics 64% for barbiturate, 78% for midazolam and 68% for propofol. Variable rates of control were achieved for other therapies including other anaesthetics, antiepileptics, the use of hypothermia, immunotherapy, the ketogenic diet, magnesium, pyridoxine, immunotherapy, electroconvulsive therapy (ECT), cerebrospinal fluid (CFS) drainage, VNS and emergency resective surgery. The reported mortality rate of this stage of status epilepticus was 35% and a further 13% of patients were left with severe neurological deficit. Conclusion: There is a remarkable dearth of information about the outcome of the various therapies used, often widely so, to control refractory or super-refractory status epilepticus despite its high mortality and morbidity. There are no controlled studies, and information is based almost entirely on open, often small and retrospective, case series or case reports. Based on our findings, we make recommendations about first and second line therapy, and suggest a protocol of therapy. We also emphasis the need for an international case registry to provide better quality outcome information.
p325 EPILEPTIC STATUS IN ADULTS D. Ndoja, N. Bendo, A. Seferi, A. Kuqo, and Z. Ndroqi UHC, Tirana, Albania
Purpose: Electro-clinical-etiological finding of SE. Method: We studied 28 patients hospitalized in ICU (17 F, 11 M with median of 46 years old), from 2008 to 2010, with mean SE duration of 2 hours. Result: SE prevalence had 2 picques; in adolescentes-younger adults (10), and in older(10). All displayed generalized GSE: 11 primary PGSE, 17 secondary SGSE (Shorvon 1983). Among PGSE : 9 had convulsive, myoclonic, atonic SE in 2. In SGSE; 14 had PMS onset: hemy without, with Jaksonian march (4,2) superior 5; whereas versive and CPS onset (3,3). Etiology of PGSE; IgE in 7, metabolic in 3, eclampsy in one. Triggeref factors were AEDs changes, fever and alcol. In SGSE: vascular origin in 7, trauma 3, Tu 4, non-lesional 2, hygroma, FCD dementia in 1 respectilvely. EEG post-SE: diffuse/ bilateral in 8, lateralized 7; ictal with partial onset in 2; not available 7; normal in 3 patients. Two pt died, while BZD and PHT in refractory cases provided the good outcome, in others. Conclusion: SGSE prevailed more than PGSE. In PGSE, IGE were more frequent than metabolic SE. in SGSE the vascular etiology was more frequent than trauma and Tu, then than DA, MCD, and non-lesional. EEG : diffuse/ bilateral more than lateralized, normal finding.

p324 EEG AND MRI FINDINGS IN SUPER REFRACTORY STATUS EPILEPTICUS DUE TO UNKNOWN UNDERLYING ETIOLOGY A. Ferrari, P. Renzetti, M. Ferretti, F. Piccardo, N. Mavilio, and G. A. Ottonello IRCSS A.O.U San Martino, Genova, Italy
Purpose: Super Refractory Status Epilepticus is a stage of Refractory Status Epilpticus and it is characterized by unresponsiveness to initial anesthetic therapy. It is defined as a condition that continues or recurs 24 hours or more after the onset of anesthesia. Method: We report the case of 40-years-old man affected by cerebellar atrophy who suffered myoclonic seizures with onset at 3 years old. He
p326 A CASE OF SEVERE FORM OF PANDAS-LIKE COURSE L. C. Heberle*, D. Neubauer, A. Altawari*, and N. Alothman* *Al Sabah Hospital, Kuwait, Kuwait; and University Children's Hospital Ljubljana, Ljubljana, Slovenia
Purpose: Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infections (PANDAS) presents as a spectrum of postinfectious neurological disease that extends well beyond Syndenham chorea and includes different neuropsychiatric conditions including complex tic disorders and obsessive-compulsive behavior. Method: We describe a boy with an extremely severe and life-threatening course who responded well to immunotherapy but is left with residual epilepsy and depression. Result: K. was 11-year old boy who had had tics one year before admission due to low grade fever, throat infection and progressive lethargy with absence like attacks followed by epileptic status and apneas. After
96 Abstracts
institution of anticonvulsive treatment and antibiotics seizures subsided and a full-blown clinical picture emerged with very frequent complex tics, fidgety and psychiatric behavior to be soon followed by another period of status epilepticus and apneas necessitating intubation and intensive care. Results showed very high titers of ASOT (3200 IU/ml), MRI brain faint thalamic changes, CSF study was normal. EEG showed progressive slowing of background activity which later normalized. Despite no epileptiform discharges he had occasional focal seizures. With penicillin prophylaxis, combined treatment with immunoglobulins and methylprednisolone the child gradually improved, however he still has occasional epileptic seizures, tics and depressive behavior. His recent minimental test proved normal result. Conclusion: We believe that this boy had s severe form of PANDASlike condition, presenting also as epileptic statuses, finaly leading to residual epilepsy and depressive behaviour. Purpose: Convulsive Status Epilepticus (CSE) is one of the most common neurological emergencies in children with high mortality and morbidity. Prognostic value of risk factors as age, etiology, duration, quality of pre hospital treatment is not well studied. Purpose- to study correlation of duration, etiology and type of status on outcome. Also Effect of quality of pre hospital treatment on short term outcome. Method: Hospital based study. Children admitted to Central Children Hospital with CSE from 01.01.09 till 31.12.10 were evaluated and monitored for at least 12 months. Result: Among 870 hospital admissions, were 46 cases of CSE (5.3%). Average age was 4.9 years. In 5 cases status was first manifestation of epilepsy. 20 patients had previous history of epilepsy, 9 were on AED. 5 had drug resistant epilepsies. 12 patients had developmental delay. Status was focal in 24 and generalized in 22 cases. In 8 cases CSE was febrile, infections of CNS in 7 cases. Stroke was manifested with CSE in 3 cases (2 ischemic, one hemorrhagic) . Duration of CSE varied from 30180 min. mean 50.5. Mortality rate was 4.3% (2 patients). Data revealed poor pre hospital care over treatment with BZD. All patients received 12 doses of BZD, 14 patients 3 or 4 doses. Conclusion: Analysis of data showed no correlation of outcome with age, type of epilepsy, duration of status. There was negative correlation between prehospital care and outcome. Patients receiving 34 doses of BZD at prehospital level had longer stay on ventilation and worst short term outcome (p < 0.001).
p327 EFFICACY OF INTRAVENOUS LACOSAMIDE IN SYMPTOMATIC FOCAL MOTOR STATUS EPILEPTICUS: A CLINICAL AND VIDEO-POLYGRAPHIC STUDY M. Trivisano, G. DOrsi, M. G. Pascarella, F. Pacillo, M. Ferrara, E. Carapelle, C. Luisi, M. T. Di Claudio, and L. M. Specchio Epilepsy Center Clinic of Nervous System Diseases, University of Foggia, Riuniti Hospital, Foggia, Italy
Purpose: To evaluate efficacy and tolerability of intravenous lacosamide (LCM) in the treatment of Non-Convulsive Status Epilepticus (NCSE) after failure of conventional therapy. Method: Patients presented with refractory NCSE underwent LCM i.v. therapy and a long-term video-EEG/polygraphic monitoring before and after LCM treatment. Result: Three patients (2 female, 1 male), aged between 60 and 70, with symptomatic (gliomatosis cerebri, brain metastasis of lung adenocarcinoma, ischemic stroke) focal motor status epilepticus were investigated. The first patient showed left fronto-central polyspike-and-wave activities associated with tonic contraction of right orbicularis oris followed by tonic-clonic activity in the right masseter and orbicularis oris, hypersalivation and aphasia. The second one presented with aphasia and tonic-clonic activity of right extensor hand muscles associated with left fronto-temporal epileptic discharge. The third one had repetitive left leg tonic-clonic activity with epileptic discharge over the vertex and right anterior region. All patients achieved a clinical and polygraphic disappearance of the focal motor status within 24 hours since the first administration of 400 mg of LCM i.v. after an ineffective treatment with DZP (10 mg i.v.) and LEV (3000 mg i.v.). In all patients the treatment with PHT was not possible because of hypotension in two and sinus bradycardia in one. All patients did not have any seizures with a maintaining dose of 400 mg/day. Conclusion: Our clinical and polygraphic study suggest that LCM i.v. may be effective in the treatment of refractory focal motor NCSE, but larger studies are needed to confirm the efficacy of LCM in the treatment of this type of NCSE.
p329 UTILITY OF ONE HOUR PORTABLE EEG RECORDING IN DETECTION AND MANAGEMENT OF NON-CONVULSIVE STATUS EPILEPTICUS IN PATIENTS WITH ALTERED SENSORIUM IN A RURAL-BASED ICU IN RESOURCE LIMITED SETTINGS S. D. Desai, P. B. Shah, B. S. Vaishnnav, D. S. Desai, S. Sheth, and J. Mannari Pramukhswami Medical College and Shree Krishna Hospital, Anand, Gujarat, India
Purpose: To identify the prevalence of non-convulsive status epilepticus [NCSE] in patients with altered sensorium in a rural based medical intensive care unit [ICU] using one hour portable Electroencephalography [EEG] record and to assess its utility/ impact by assessing the number of patients in whom treatment decisions changed after the portable EEG record. Method: 70 adult patients admitted in medical ICU with altered sensorium underwent one hour EEG for assessing presence of NCSE using preset defined clinical and EEG criteria. We assessed the relationship between demographic characteristics, clinical features and the presence of NCSE. We also assessed the number of patients in whom EEG recording lead to change in treatment by addition/ change/modification/stopping of anti-epileptic drug [AED] therapy and assessed its relationship to overall patient outcome. Result: NCSE was present in 13(18.57%) of our cohort of 70 patients. The common aetiologies for altered sensorium were metabolic encephalopathy (52.94%), intracranial infections (17.64%) and stroke(5.84%). Treatment was changed in 16 patients (22.85%) after EEG recording, of whom 11(68.75%) had NCSE and required addition of AED. After changing treatment clinical improvement occurred in 7 patients (43.75%). Conclusion: Our pilot study shows that one hour portable EEG in resource limited settings can identify NCSE in significant number of patients with altered sensorium in medical ICU and lead to treatment change and better outcome.
p328 CONVULSIVE STATUS EPILEPTICUS IN CHILDRENPREDICTORS OF OUTCOME N. Tatishvili, and T. Shatirishvili Central Children Hospital, Tbilisi, Georgia
97 Abstracts
p330 ATYPICAL ABSENCE NONCONVULSIVE STATUS EPILEPTICUS IN CHILDREN WITH MEDULLOBLASTOMA AFTER CRANIOSPINAL IRRADIATION; A POSSIBLE LENNOX-GASTAUT SYNDROME MIMICKING ENTITY I. Maestro Saiz, A. B. Anaya-Chen, J. M. Prats Vias, A. Iglesias Martinez, B. Mateos, L. Perez, and I. Yurrebaso Cruces University Hospital, Barakaldo, Spain
Purpose: We describe three cases of pediatric-aged patients diagnosed of medulloblastoma who presented atypical absence nonconvulsive status epilepticus probably related to radiotherapy. Method: Three children; 10 year-old-boy, 11 year-old-girl and 11 yearold-boy, previously diagnosed of medulloblastoma with complete response to treatment after chemotherapy and craniospinal irradiation who presented tonic or generalized tonic-clonic seizures in the course of the disease, were admitted in our institution with the clinical suspicion of tumor-recurrence after presenting acute impairment of mental status. Patients underwent various diagnostic techniques such as structural MRI, lumbar puncture, blood and cerebrospinal fluid (CSF) cultures and videoelectroencephalographic (EEG) recording. Result: In all three patients, diagnostic structural MRI did not show any significant change comparing with previous exams and other tests discarded tumor recurrence. Video-EEG showed continuous generalized slow spike-wave complexes in all children with no clinical changes of basal state during the recording. Three patients were diagnosed of atypical absence nonconvulsive status epilepticus and were treated with LEV in two cases and with VPA in the other one, with complete remission of symptoms and epileptiform activity. Conclusion: Despite medulloblastomas are tumors arising from cerebellum, epileptic seizures are common in the course of the disease, probably related with radiotherapy which is an essential component in postoperative management. Atypical absence nonconvulsive status epilepticus is an unexpected late sequel that must be suspected, probably also related with cerebrospinal radiation, classically also considered as one of the etiologies of Lennox-Gastaut syndrome. Early suspicion, diagnosis and treatment of this entity, could prevent secondary morbidity and mortality in these oncologic patients. and/or prolonged refractory status) had complications compared with 30% of those not admitted to ICU (p < 0.05). Of 17 previously treated patients, 10 were monotherapy, 7 polytherapy. 29.4% 1st generation drugs, 41.2% 2nd and 29.4% both. Prior untreated patients: 85.7% initiated monotherapy (100% 1st generation). Of those treated 33.3% increased number of drugs, decreased 6%. The most widely used drug was valproic acid monotherapy (on 50%, high 40%) and levetiracetam in combination (on 100% high 81%). Conclusion: Focal complexwas the most frequent NCSE. There were more complications in patients with altered level of consciousness and refractory status.
p332 EFFICACY OF DIFFERENT THERAPEUTIC AGENTS IN STATUS EPILEPTICUS J. Rsche, K. Rantsch, U. Walter, and R. Benecke Universittsmedizin Rostock, Rostock, Germany
Purpose: We evaluated the efficacy of different antiepileptic drugs and narcosis in different forms of status epilepticus in a retrospective study. Method: We reviewed the medical charts of all patients, who were treated for status epilepticus in our department from January 2000 to December 2009. The last drug given before termination of status epilepticus was considered as termination drug. The quotient of status epilepticus episodes in which an antiepileptic drug or narcosis was the termination drug and all status epilepticus episodes in which the therapeutic agent had been used was considered as efficacy rate. Differences in efficacy were tested for significance by chi-square-tests. Result: 167 episodes of status epilepticus in 118 patients (58 female, 60 male) could be evaluated. 9 patients died without termination of status epilepticus. Efficacy rates ranged from 20% (Lacosamid) to 51% (Clonazepam) and 68% (narcosis). Efficacy of Phenytoin (44 episodes), Valproate (53 episodes), Levetiracetam (41 episodes) and Lacosamid (10 episodes) did not differ significantly. Clonazepam (121 episodes) was more efficient than other benzodiazepines (p < 0.000008) and i.v. antiepileptic drugs (p < 0.04). Narcosis was more efficient than i.v. antiepileptic drugs (p < 0.005). But its efficiency was lower in nonconvulsive status epilepticus than in status of generalized tonic-clonic seizures (p < 0.02). Conclusion: The results of this retrospective study are confounded by many factors. Nevertheless Clonazepam was more effective in the termination of status epilepticus than other antiepileptic drugs und narcosis worked better in generalized tonic-clonic status epilepticus than in nonconvulsive status epilepticus.
p331 NON-CONVULSIVE STATUS EPILEPTICUS: PROFILE OF PATIENTS ADMITED ON A TERTIARY HOSPITAL M. J. Aguilar Amat Prior Hospital Universitario La Paz, Madrid, Spain
Purpose: Description of patients with non-convulsive status epilepticus (NCSE). To assess factors associated with mortality, complications and treatment. Method: Retrospective observational study of patients admitted for NCSE between 20082010. We analyzed demographic data, history of epilepsy, treatment, type NCSE and variables associated with mortality and complications. Result: 30 patients (60% M). Mean age 62 years. Previous epilepsy : 85% and 15% generalized. 70% symptomatic. 17 patients had focal complex NCSE, 7 and 6 simple focal SENC status of absence. 15% caused by changes in medication. 46.7% had complications (64% respiratory) and 6 patients died. No significant differences in complications and mortality in age, sex, type, etiology and treatment of epilepsy, or type of NCSE. 70% of patients admitted to ICU (due to impairment on level of consciousness

p333 NON-CONVULSIVE STATUS EPILEPTICUS: PREVALENCE, PRECIPITATING FACTORS, CLINICAL MANIFESTATIONS, RADIOLOGICAL, ELECTROENCEPHALOGRAPHIC FINDINGS AND MORTALITY IN A TERTIARY CARE HOSPITAL IN MEXICO V. Gijn-Mitre*, M. Alonso-Vanegas, and H. Sentes Madrid *Instituto Nacional de Ciencias Mdicas y Nutricin Salvador Zubirn, Mxico D.F, Mexico; Instituto Nacional de Neurologa y Neurociruga Manuel Velasco Suarez, Mexico
98 Abstracts
City, Mexico; and Instituto Nacional de Nutricin y Ciencias Mdicas Salvador Zubirn, Distrito Federal, Mexico
Purpose: To determine the prevalence, causes, clinical features, radiological and EEG, treatment and mortality in patients with non-convulsive status epilepticus (NCSE) in the Instituto Nacional de Ciencias Mdicas y Nutricin Salvador Zubirn. Method: A retrospective, descriptive, observational study. Result: Seventy-nine cases of status epilepticus (SE) of which 8 were for NCSE (10.12%), 5 women, mean age 52 years, 3 had a family history of epilepsy, 2 history of neonatal hypoxia, 5 had reported seizures previously, 2 by migralepsia, 1 traumatic brain injury, 1 as a complication of chronic meningitis from tuberculosis and another one for cryptogenic epilepsy, 2 had previously presented convulsive SE. 6 had NCSE admission. The causes were diverse: meningoencephalitis (2), metabolic (2), suspension of drugs (1), migralepsia (2), 1 after cesticide treatment, 4 had initially behavior alterations, temporal disorientation and focal seizures, 2 tonic-clonic seizures. The average Glasgow was 9, all cases showed alteration of the alert and the duration was longer than 30 minutes (prolonged SE) in 5 patient. The neuroimaging was abnormal in 3 patients and the EEG showed unilateral epileptic activity in 6 and bilateral in 2. The treatment was based on BZD and PHT in all patients, 4 underwent barbiturate coma, 2 had refractory SE. Mortality was 12.5% (1) and 1 patient was left with serious neurological sequelae. Conclusion: A history of epilepsy was common in patients with NCSE, the alert and conduct disorders were the main clinical manifestations, mortality appeared similar to that reported in the literature.
p335 DELAY IN DIAGNOSIS: A NEW PREDICTOR OF REFRACTORINESS AND MORTALITY IN NONCONVULSIVE STATUS EPILEPTICUS? M. Sanchez, L. Romano, F. Latini, P. Alvarez, M. Ayala, A. Aleman, I. Etchepareborda, E. Sottano, P. Ioli, and S. Gonorazky Hospital Privado de Comunidad, Mar del Plata, Argentina
Purpose: The mortality of non-convulsive status epilepticus (NCSE) ranges from 18 to 52% depending on the presence of different prognostic factors. Recognizing these factors in NCSE helps to differentiate the group of patients requiring special care or benefit from specific therapeutic strategies. Objective: To evaluate the delay in the diagnosis of NCSE as a predictor in refractoriness and mortality at day 30 in patients with NCSE. Method: In this prospective study we recorded all cases of NCSE between April 2007 and March 2011, in patients 21 years. The baseline prognostic variables were analyzed using stepwise logistic regression analysis. Result: There were 125 patients with NCSE. The median age was 76 years and 65% were women. The etiology of NCSE was unknown in 9%, remote symptomatic in 10%, and in 81% acute symptomatic. The median diagnostic delay time was 48 hours. The mortality rate was 37%. After analysis of all the aforementioned variables using stepwise logistic regression analysis, only delayed diagnosis >56 hs was an independent predictor of refractoriness(OR:4.7, p = 0.0002). Acute symptomatic etiology (OR:7.2, p = 0.003), partial NCSE (OR:3.9, p = 0.008), delayed diagnosis >56 hs (OR:4.6, p = 0.001), and refractoriness (OR:5.3, p = 0.0008) were independent predictors of mortality at day 30 in patients with NCSE. Conclusion: Our data suggest that a delayed diagnosis is an independent variable of refractoriness and mortality in patients with NCSE. We propose that delayed diagnosis should be included as a prognostic variable when analyzing the efficiency of different treatments for this entity. Our findings should be confirmed in future prospective studies in different populations.
p334 SUCCESSFUL USE OF KETAMINE IN PEDIATRIC SUPER-REFRACTORY STATUS EPILEPTICUS CASE REPORT C. Andrade*, S. Frana*, M. Sampaio*, A. Ribeiro, J. M. Oliveira*, J. A. M. Ribeiro*, and R. Rego *Hospital de So Joo, Porto, Portugal; and Servico de Neurofisiologia, Porto, Portugal
Purpose: Treatment failure in refractory status epilepticus (SE) and progression to super-refractory SE may be related to a depletion of GABA receptors, decreasing the efficacy of most general anesthetic drugs. Ketamine, an antagonist of NMDA receptors, seems therefore a rational option in super-refractory SE. We report our experience using this drug on a pediatric case of super-refractory SE. Method: Clinical case report. Result: 5 year-old girl with DiGeorge syndrome, extensive bi-hemispheric polymicrogyria, severe psychomotor retardation and epilepsy. During the course of a respiratory infection the patient developed generalized myoclonic SE. She was admitted in the ICU, where baseline anti-epileptic drug treatment was optimized and burst-suppression was achieved with midazolam, propofol, thiopental or combinations of these drugs. However, tapering anesthetics repeatedly resulted in clinical and EEG evidence of recurrent SE. After 30 days of ICU stay, ketamine was tried, with rapid clinical and EEG response, allowing UCI discharge one week later. At the 2-month follow-up visit, the patient had complete clinical recovery, with a return to her baseline neurological status. Conclusion: In this case of pediatric super-refractory SE, the response to ketamine was prompt and sustained, despite being initiated one month after ICU admission. We speculate if an earlier use of this drug might have aborted the SE sooner. Further case reports and clinical trials of ketamine in super-refractory SE are needed.
p336 IN HOSPITAL DEATHS ASSOCIATED WITH STATUS EPILEPTICUS: A DR FOSTER ALERT E. F. Cant*, G. Cook, C. Wasson, and P. Talbot *Manchester University, Manchester, UK; Stepping Hill Hospital, Manchester, UK; and Salford Royal Hospital, Manchester, UK
Purpose: Dr Foster highlighted Stepping Hill hospital as having an abnormally high number of deaths among patients with a primary discharge code of status epilepticus (SE) from 20002011. This audit focused on why this occurred and if improvements could be made to prevent this in the future. Method: The notes of 15 out of the 17 patients who died with a discharge diagnosis code of G41 (SE) from 20002011 were audited assessing the care given in hospital and to determine whether the death was avoidable. Result: All patients were admitted in SE and had a mean age of 76. They were found to have significant comorbidities such as dementia, cerebrovascular disease and excess alcohol consumption. All had appropriate immediate management against guidelines. 8 patients were given phenytoin during admission;4 did not have their serum levels monitored and 4
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had sub-therapeutic serum levels. 1 patient's ITU admission was delayed, 1 other patient may have been appropriate for ITU but referral was not discussed. 1 died from a pulmonary embolism. Conclusion: These deaths were unavoidable due to severe underlying disease triggering the seizures. The alert was due to inaccurate discharge coding where the primary diagnosis was inappropriately given as SE. However the audit of the management of SE highlighted areas for improvement. These included a need for closer and more rigorous monitoring of therapeutic Phenytoin levels; greater patient review for ICU and quicker transfer; optimising DVT prophylaxis early in SE management and the consistent use of measures to prevent aspiration. Updated guidelines are being implemented. 15 cases became refractory despite aggressive treatment with IV Benzodiazepines, Phenytoin, Valproate and Levetiracetam. 1 g Methyprednisolone for 5 days was administered to all 15 cases. In the meantime, the aetiology of NCSE was verified. Frequent follow-up EEG recordings were performed. Result: 7 patients clinically deteriorated, their EEG patterns remained unchanged and died within weeks or months afterwards. The mean age was 68.5 and the underlying disease was brain tumor (4 cases), herpes simplex encephalitis (HSE) (1), acute disseminated encephalomyelitis (ADEM) (1) and Creutzfeldt Jacob disease (1). Clinical improvement and EEG normalization was evident in 8 cases. The mean age was 48 and the underlying disease was neurosarcoidosis (1 case), Systemic Lupus Erythematosus (1), ADEM (1), stroke (2), Alzheimer's Disease (1) and HSE (1). Conclusion: High-dosage corticosteroid treatment should always be considered in the treatment of refractory NCSE. Furthermore, the clinical outcome is strongly influenced by the underlying disease and the patient's age.
p337 THE IMPACT OF NEWER ANTIEPILEPTIC DRUGS IN THE TREATMENT OF STATUS EPILEPTICUS A. O. Rossetti, and L. Jaques CHUV, Lausanne, Switzerland
Purpose: Newer antiepileptic drugs (AED) are increasingly prescribed, and seem to have a comparable efficacy as the classical AED in patients living with epilepsy; however, their impact on status epilepticus (SE) prognosis has received little attention. Method: In our prospective SE registry (200610) we assessed the use of newer AED (for this purpose: levetiracetam, pregabalin, topiramate, lacosamide) over time, and its relationship to outcome (return to clinical baseline conditions, new handicap, or death). We adjusted for recognized SE outcome predictors (Status Epilepticus Severity Score, STESS; potentially fatal etiology), and the use of >2 AED for a given SE episode. Result: Newer AED were used more often towards the end of the study period (42% versus 30% episodes), and more frequently in severe and difficult to treat episodes. However, after adjustment for SE etiology, STESS, and medication number, newer AED resulted independently related to reduced likelihood of return to baseline (p < 0.01), but not to increased mortality. STESS and etiology were robustly related to both outcomes (p < 0.01 for each), while prescription of >2 AED was only related to lower chance of return to baseline (p = 0.03). Conclusion: Despite increase in the use of newer AED, our findings suggest that SE prognosis has not been improved. This appears similar to recent analyses on patients with refractory epilepsy, and corroborates the hypothesis that SE prognosis is mainly determined by its biological background. Since newer AED are more expensive, prospective trials showing their superiority (at least regarding side effects) appear mandatory to justify their use in this setting.
p339 NONCONVULSIVE STATUS EPILEPTICUS IN NORMOGLICEMIC DIABETIC PATIENTS J. Klem*, L. Stancetic Bacvanin, and A. Bacvanin *General Hospital, Sombor, Serbia; and General Hospital, Sremska Mitrovica, Serbia
Purpose: Nonconvulsive status epilepticus (NCSE) causes many different neurologic deficits, particularly in alertness and cognitive function, and may be one of the most frequently missed diagnoses in patients with altered neurologic function. NCSE may constitute one quarter up to 40% of all status epilepticus. Diabet type 1 can cause an acute confusional state due to NCSE. Method: In our two 48 and 65 years-old patients, the lack of a predominant motor component differentiates NCSE from convulsive status epilepticus. First they were seen with bizarre, and fluctuating behaviour from lack of responsiveness to confusion with oral or manual automatisms lasting 48 hours before hospital addmision. During hospitalization altered mental status, subtle twitching, blinking, nystagmus, stupor and confusion were seen. They were diabetic. They had normal blood sugar levels . Both patients have had history of often comatose hypoglicemic states with generalized convulsiones due to low blood sugar levels. Result: laboratory screening including normal blood sugar levels showed no abnormalities . EEG showed prolonged repetitive complex partial seizures and/or continuous seizure activity in both patients. Computed tomography showed reductive cortical changes . After phenobarbital administration in the next 34 days, they became more responsive, and oral or manual automatism slowly resolved . Up to next 10 days after NCSE they were amnestic, and their verbal function recovery delayed. Conclusion: NCSE may occur in patients with diverse clinical diagnoses. Preventing missed diagnosis, EEG should be perfomed in all patients with unexplained reccurent altered mental status, stupor and confusion.
p338 CORTICOSTEROIDS IN THE TREATMENT OF NONCONVULSIVE STATUS EPILEPTICUS (NCSE) D. Tsiptsios, D. Kiourtidis, T. Tsironis, P. Petrou, E. Ameridis, M. Krommida, A. Mastrokosta, E. Markousi, G. Deretzi, E. Koutlas, J. Rudolf, A. Tichalas, G. Xiromerisiou, X. Fitsioris, and I. Tsiptsios Papageorgiou General Hospital, Thessaloniki, Greece
Purpose: NCSE is a neurological condition that is often missed or misdiagnosed in emergency neurology when immediate EEG recording is not available. Due to this fact NCSE often becomes refractory, ie lasting >24 hours. The aim of this study is to investigate the efficacy of high-dosage corticosteroid treatment in refractory NCSE. Method: During a 19 month period, June 2010 February 2012, 27 patients were diagnosed with NCSE based on EEG patterns, such as PLEDs, GPEDs and BiPEDs.
p340 FOCAL MYOCLONUS STATUS IS NOT UNCOMMON MANIFESTATION IN THE PATIENTS WITH ANTIFOSFOLIPID SYNDROME L. M. Stancetic Bacvanin*, J. Klem, and A. G. Bacvanin* *Srem.Mitrovica, Serbia; and Sombor, Serbia
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Purpose: We present patients with antifosfpolipid syndrome (APS) and focal myoclonic status. Method: A medical files of 25 patients with APS (16 femals and 9 males) that were hospitalized from April 1999 to August 2010 in our department were evaluated. Result: We found four patients (16%) that had prolonged myoclonic seizures in their medical history. Myoclonic status lasted from 12 hours to 10 days . Half of the patients had secondary APS. Reccurent palatal myoclonus had 46 years-old female with brainstem vasculitic changes, 52 years-old female had hemiclonic status and bilateral brachial spinal myoclonic yerks.. Two men (52 and 65 years-old) had prolonged hemifacial myoclonic yearks . All patients were MRA pozitive to focal cerebral ischemia and focal cortical atrophy changes and all had increased titers of anticardiolipin antibodies (IgG 24,352 GPLU/ml; IgM 1462,9 MPLU/ml). Patient with Epilepsia partialis continua Kozevnikow had excessive unilateral or bilateral frontocentral polyspikes and spike waves discharges . During spinal myoclonic yearks there was no EEG-epileptic activity. MRI showed left focal frontotemporal atrophy. Patient with palatal myoclonus had frontocentroparietal polyspikes, and frontal slow activity on its EEG. MRI showed lacunar vascular supratentorial and brainstem ischemic lesions. Two men with hemifacial myoclonia had no specific EEG changes after the attacks. One had luetic gummous formation, the other microlacunar and extended predominantely temporal cortical atrophy. Conclusion: In this group four patients (16%) had prolonged myoclonic seuzures . Seizures were partially ameliorated by a complex of medications: anticonvulsants and pulse corticosteroid therapy.
p342 USE OF INTRAVENOUS LACOSAMIDE IN STATUS EPILEPTICUS AND CLUSTER SEIZURES Y. Handouk, C. Bomprezzi, C. Minardi, S. Malag, S. Morresi, and A. Mauro U.O. Neurologia, Cesena, Italy
Purpose: To test the efficacy and safety of the intravenous drug formulation in SE and cluster seizures. Some antiepileptic drugs (AEDs) used in status epilepticus (SE) are associated with potential respiratory and cardiovascular complications. Lacosamide (LCM), a new AED, has an intravenous formulation with a potential role in the treatment of SE. Method: 11 patients with symptomatic epilepsy (6 female and 5 male; mean age 66 (2390); 8 with SE and 3 with cluster seizures), was treated, after failure of other AEDs, with simultaneous administration of intravenous and oral LCM for two days (200 mg intravenous + 50 mg oral LCM twice daily), then switched to oral LCM (400 mg daily). Result: EEG improvement occured in the first 24 hours after the beginning of LCM therapy. All patients were responsive with no serious adverse event, except two old patients who died for severe comorbidities. Conclusion: LCM could be efficacious and safe in the treatment of SE.

p341 SUPER-REFRACTORY STATUS-EPILEPTICUS: THERE IS ALWAYS HOPE Z. Agirre-Arrizubieta*, and N. Moran *King's College Hospital, London, UK; and East Kent Hospitals NHS University Foundation Trust, Canterbury, Kent, UK
Purpose: Two male patients, 20 and 28 years, presented with acute seizures and encephalopathy. Multiple brain MRI examinations were normal and extensive metabolic, haematological and serological tests were negative. Cerebrospinal fluid (protein, glucose, microbiology, oligoclonal bands) was normal except patient A had 7 white cells/ml. Both received broad spectrum antimicrobials. Method: In patient A generalized tonic-clonic seizures led to ventilation and ultimately treatment with six anti-epileptic drugs (AED). The EEG initially showed a suppression burst pattern; following reduction of sedation, status epilepticus (SE) with a right temporal focus, plus generalized periodic epileptiform discharges (GPEDs). It was some three months before control was achieved but recovery was good with mild amnesia only. Result: Patient B had focal seizures with secondary generalization and then SE. The EEG revealed a right anterior focus, generalized seizures and GPEDs. He was ventilated and subsequent treatment comprised seven AED, including thiopentone, plus human pooled immunoglobulin and plasmapheresis. Six months following presentation, deep brain stimulation as associated with substantial improvement in the EEG but the patient was left in a persistent vegetative state. Conclusion: Each patient displayed similar clinical pictures of obscure aetiology with super-refractory SE (SRSE) (Shorvon S. Epilepsia. 2011 Oct;52 Suppl 8:536). However, the outcomes were radically different. Even when prolonged and of unknown aetiology, SRSE should not be regarded as hopeless.
p343 THE EFFECTS OF ANTIEPILEPTIC DRUGS ON THE VOLTAGE-GATED SODIUM CHANNELS OF THE PERIPHERAL MYELINATED NERVE FIBERS OF THE ADULT RAT G. Zafeiridou*, A. Kagiava, M. Spilioti, A. Karlovasitou, and G. Theophilidis *Aristotle University, Thessaloniki, Greece; School of Biology, Aristotle University, Thessaloniki, Greece; and Medical School, Aristotle University, Thessaloniki, Greece
Purpose: One of the major targets of many widely used antiepileptic drugs (AEDs) are voltage-gated sodium channels (VGSCs). Some of these drugs have been associated with effects on the peripheral nerve function. In this study we investigated in vitro the effects of three AEDs on the VGSCs of the peripheral myelinated nerve fibres, of the adult rat. Method: The effects of phenytoin (PHT), topiramate (TPM) and lacosamide (LCM) were tested on the electrophysiological properties of the Wistar rat isolated sciatic nerve. Result: Incubation of the sciatic nerve fibers in therapeutic doses (72.9, 36.46, 18.23 lM) of PHT, caused a gradual decreased in the amplitude of the CAP and increase in the latency (p < 0.05). TPM was applied at much higher concentrations than the therapeutic doses (178.5 Mm, 500 lM), yet it had no effect on the amplitude of the CAP and the latency (p > 0.05). LCS was also investigated at high concentrations (100, 250, 400, 500 lM) but in this case, an acute, dose-respondent, decrease in the amplitude of the CAP was caused (p < 0.001). This intense decrease in amplitude was followed by a similar increase in the latency (p < 0.001). Conclusion: These findings confirm the adverse effect of PHT, in the peripheral nerve function even in very low concentrations. In contrast, LCS had effects at concentrations much higher than the therapeutic doses. LCS also demonstrates a different mode of action that causes rapid
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and acute alteration on the electrophysiological properties of the peripheral nerve. Finally, TPM had no effects on the peripheral nerve function, although high concentrations were used. where characteristic slow potential shifts, but no reduction of diffusion tensor magnetic resonance (MR) signal and MAP-2 immuno-staining (typical of ischemic core) was observed. Recording of responses evoked by low- and high-frequency stimulations of the lateral olfactory tract showed no excitability changes in the early hours that follow ischemia in the olfactory cortical areas supplied by ACAs. Conclusion: The absence of early hyperexcitability changes in an isolated whole brain model of ischemia, strongly suggests that brain anoxia per se does not contribute to the generation of early seizures. These findings support the view that blood-borne events (such as hemorrhage and inflammation) may play a major role in early postischemic seizures.
p344 A NEW IN VITRO MODEL OF HIGH FREQUENCY ELECTRICAL STIMULUS INDUCED SEIZURE AND EFFECTS OF STANDARD ANTIEPILEPTIC DRUGS A. Wahab*, K. Albus, and U. Heinemann *University of Karachi, Karachi, Pakistan; and Charit Universitatsmedizin Berlin, Berlin, Germany
Purpose: In the hippocampus intense high frequency electrical stimulation induces a long lasting rhythmic synchronization (primary afterdischarge). In order to examine the suitability of primary afterdischarges (PADs) in organotypic hippocampal slice cultures (OHSCs) as an in vitro model of evoked seizures we have investigated in detail the sensitivity of PADs to standard antiepileptic drugs (AEDs). Method: OHSCs were prepared using interface culture method from eight to 11 day old Wistar rats. A PAD in CA1 was elicited by stimulating the stratum radiatum with an intensity of two times that required to elicit a maximal population spike. The effects of AEDs on the duration and on frequency properties of PADs and the tonic-like and clonic-like subdivisions of PADs were determined and EC50 values were calculated from concentration response curves. Result: All the standard AEDs except ethosuximide reduced the durations of PADs and tonic-like and clonic-like subdivisions of PADs. The effects were concentration dependent and reversible. The effects on subdivisions of PADs differed between AEDs. Carbamazepine and phenytoin shortened the tonic-like and clonic like subdivisions at similar proportions whereas phenobarbital, diazepam and valproic acid preferentially shortened the clonic-like subdivision. Diazepam at low concentrations increased the duration of tonic- like subdivisions an effect not seen with the other AEDs. The suppressive effects of AEDs on frequency properties observed only at higher concentrations. Conclusion: We conclude that the PAD test in OHSCs is a suitable in vitro model of evoked seizures. The validity of this model could be further examined by studying the effects of newer AEDs.
p346 INVESTIGATION OF ANTIEPILEPTIC DRUG TRANSPORT BY SOLUTE CARRIERS OATP1A2 AND MCT1 H. L. Jones, D. Dickens, A. Owen, M. Pirmohamed, and G. J. Sills University of Liverpool, Liverpool, UK
Purpose: We have investigated the trans-membrane transport of antiepileptic drugs (AEDs) by organic anion transporting polypeptide 1A2 (OATP1A2) and monocarboxylic acid transporter 1 (MCT1), members of the solute carrier super-family. Method: Xenopus laevis oocytes were transfected with OATP1A2/ MCT1 cRNA and transport determined three days thereafter by comparison of the uptake of radiolabelled AEDs (25 mM phenytoin, 20 mM carbamazepine, 300 mM sodium valproate, 10 mM lamotrigine, 10 mM gabapentin, 10 mM topiramate and 6 mM levetiracetam) in transfected vs untransfected oocytes. Estrone-3-sulfate (1 lM) and lactic acid (5 lM) were employed as positive control compounds for OATP1A2 and MCT1, respectively. Results from at least three independent replicates, each employing eight oocytes per group, were expressed as mean (SEM) percentage of control transport in untransfected oocytes. Result: Transport of estrone-3-sulphate in OATP1A2-transfected oocytes was 1326 171% of that observed in untransfected controls (p < 0.01). Transport of lactic acid in MCT1-transfected oocytes was 2607 240% of that observed in untransfected controls (p < 0.001). There were only minor changes in the mean transport of AEDs in transfected vs untransfected oocytes for both OATP1A2 (98.1 8.2% phenytoin, 91.3 2.8% carbamazepine, 111 7.3% sodium valproate, 128 7.7% lamotrigine, 104 17% gabapentin, 111 6.5% topiramate, 94.5 7.0% levetiracetam) and MCT1 (108 2.6% phenytoin, 110 4.1% carbamazepine, 94.0 3.8% sodium valproate, 77.6 5.7% lamotrigine, 164 15% gabapentin, 110 3.0% topiramate, 115 5.9% levetiracetam), none of which reached statistical significance. Conclusion: None of the seven AEDs investigated in this study appeared to be a substrate for either OATP1A2- or MCT1-mediated transport in selectively transfected Xenopus laevis oocytes. These findings discount the involvement of OATP1A2 and MCT1 in the transmembrane transport of AEDs.
p345 PENUMBRA REGION EXCITABILITY IS NOT ENHANCED ACUTELY AFTER CEREBRAL ISCHEMIA IN THE IN VITRO ISOLATED GUINEA PIG BRAIN G. L. Breschi*, A. Mastropietro, I. Zucca, L. Librizzi*, and M. De Curtis *Neurological Inst. C. Besta, Milano, Italy; and I.R.C.C.S. Foundation Neurological Institute, Milan, Italy
Purpose: Early seizures are a frequent consequence of stroke. The main goal of the present study is to verify whether anoxic ischemia per se is able to induce early changes in excitability that may be a prelude to the generation of seizures and, ultimately, to epileptogenesis. Excitability changes in the very acute postischemic phase are here analyzed in a new model of ischemia developed in the isolated guinea pig brain preparation. Method: Permanent bilateral occlusion of the anterior cerebral arteries (ACAs) was performed in the isolated guinea pig brain maintained in vitro by arterial perfusion. Magnetic resonance imaging and immunohistochemistry were utilized to identify the penumbra and core regions induced by ACA occlusion (ACAo). Slow potentials and evoked responses recorded in olfactory cortices were utilized to evaluate excitability changes in the acute phase after ischemia. Result: ACAo induces a core area located in the shell of the nucleus accumbens and a region of penumbra in the underlying olfactory cortices,
p347 L-TYPE VOLTAGE GATED CALCIUM CHANNELS AFFECT SEIZURE-LIKE ACTIVITY IN AN AMBIVALENT MANNER, BUT PROMOTE THE INDUCTION OF PAROXYSMAL DEPOLARIZATION SHIFTS H. Kubista, L. Rubi, M. Lagler, P. Geier, K. Dasgupta, and S. Bhm Center of Physiology and Pharmacology Medical University of Vienna, Vienna, Austria
Purpose: The role of L-type voltage-gated calcium channels (LTCCs) as regulators of neuronal excitability relies on the coupling of
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LTCC-mediated Ca2 + -influx to Ca2 + -dependent conductances. We have shown previously that in moderate (with respect to duration and amplitude) depolarisations excitatory Ca2 + -activated nonspecific cation channel-activation prevails, which diminishes and gives way to the activation of hyperpolarising Ca2 + -dependent potassium channels as the depolarization grows. These findings prompted us to test in a similar approach the effects of LTCC modulation on (long-lasting) seizure-like activity (SLA) and on (brief) paroxysmal depolarization shifts (PDS). Method: Current-clamp experiments were performed on primary hippocampal neurons. SLA was induced by pharmacological means (e.g. lowMg2 + buffer). Induction of PDS was facilitated by caffeine. LTCC activity was modulated by BayK 8644 (LTCC agonist) and isradipine (antagonist). Result: Potentiation of LTCCs affected SLA activity in opposing manners, leading to enhancement involving plateau potentials on the one hand and reduction involving more pronounced after-hyperpolarisations on the other hand. Caffeine alone was hardly sufficient to induce PDS, but PDS were readily induced when LTCC activity was augmented by co-application of BayK. Conclusion: The bimodal effects of LTCC activation on excitability can be extended to epileptiform discharges. Hence, therapeutic reduction of LTCC activity may have little beneficial or even adverse effects on epileptic seizures. However, our data identifies enhanced activity of LTCCs as one precipitating cause of PDS. Because evidence is continuously accumulating that PDS represent important elements in epileptogenesis, LTCC inhibitors may prove useful in anti-epileptogenic therapy (supported by the Austrian Science Fund, project P-19710). Conclusion: Our results suggest that neocortical slices derived from both epileptic and tumor patients can generate multiple types of SSPA. Supragranular layers might have a leading role in the generation of SSPA. Features of SSPA were similar in epileptic and tumor slices, indicating that the emergence of neocortical SSPAs may not be related to epileptic processes.
p349 SYNAPTIC AND NON-SYNAPTIC MECHANISMS UNDERLYING SUPPRESSION OF EPILEPTIFORM ACTIVITY IN THE SUBICULAR NEURONS OF THE HIPPOCAMPUS N. Sah, and S. K. Sikdar Indian Institute of Science, Bangalore, India
Purpose: Proper balance of neuronal activity is essential for normal brain function. When the balance is compromised, neurological disorders may result. Temporal lobe epilepsy (TLE), a neurological disorder, is the most common form of adult focal epilepsy. The purpose of this study was to characterize the cellular and population dynamics of subiculum under hyperexcitable conditions. Method: 4-Amino Pyridine with reduced magnesium model of epilepsy was used in this study. Cellular and population electrical activity was recorded through whole cell patch clamp and local field potential recording techniques. Result: We have observed a distinct phenomenon in subiculum wherein an early hyperexcitable phase was followed by a late silent phase (LP) upon application of 4-AP. Silent state in pyramidal neuron was characterized by periodic inhibitory post-synaptic potentials (pIPSPs) at a frequency of 0.21 Hz. GABAA receptor mediated inhibition coincided with excitatory inputs to countermand burst discharges. Gap junctions were found to be critical for these pIPSPs generation. Fast spiking interneurons showed bursting discharges during the silent phase which might be triggering pIPSPs. The pIPSPs in pyramidal neurons ceased if the CA1-alveus was fissured. A strong coupling between CA1 discharge and subicular pIPSPs indicates an important role of CA1 region. Conclusion: We conclude that the action of feed forward inhibition concerted by gap-junctions triggered homeostatic control leading to suppression of epileptiform activity in subiculum, during the late phase (LP). Our work suggests that gap junctions are important in suppression of epileptiform activity in subiculum and argues the general notion of gap junctions being pro-epileptic.
p348 PATTERNS OF SYNCHRONOUS POPULATION ACTIVITY IN THE NEOCORTICAL TISSUE OF EPILEPTIC AND NON-EPILEPTIC TUMOR PATIENTS, IN VITRO K. Tth*, . Kandrcs, C. Szab, A. Bag, L. Er} oss, L. Entz, P. Orbay , S. Czirjk , P. Vrady , L. Sipos , T. Freund, I. Ulbert, and L. Wittner *Institution of Experimental Medicine, HAS, Budapest, Hungary; Pzmny Pter Catholic University, Budapest, Hungary; National Institute of Neuroscience, Budapest, Hungary; Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary; and Institute for Psychology, Hungarian Academy of Sciences, Budapest, Hungary
Purpose: The subiculum and hippocampal CA2 region of patients with temporal lobe epilepsy generate spontaneous population bursts in vitro, which is thought to be in relation with the epileptic reorganization. We asked whether neocortical tissue of epileptic patients generates similar spontaneous synchronous population activity (SSPA). As control we used tissue of patients with brain tumor, without epilepsy. Method: Slices were prepared from the postoperative tissue and the local field potential gradient (LFPg) was recorded. Pyramidal cells were characterised in intracellular records. Result: 48% of epileptic and 42% of tumor slices displayed SSPA. SSPAs were characterized by LFPg transient superimposed with high frequency oscillations and increased multi unit activity. The pattern of SSPAs varied among the samples, but all types were present in both epileptic and tumor samples in a similar ratio. In 60% of the cases SSPAs were observed in the supragranular layers. Cell clustering analysis showed that ~67% and ~50% of the cells increased their firing rates in relation to SSPA, in epileptic and tumor slices, respectively. Generally, the discharge rate of supragranular cells was enhanced before the LFPg peak, whereas infragranular cells fired after it. 2/3 of the intracellular recorded cells showed depolarizing responses during SSPAs.
p350 EPILEPTIFORM ACTIVITY IN THE PIRIFORM CORTEX AFTER 4AP ADMINISTRATION IN THE ISOLATED GUINEA PIG BRAIN L. M. Uva, F. Trombin, G. Carriero, and M. De Curtis Fondazione IRCCS Istituto nazionale Neurologico, Milano, Italy
Purpose: We recently showed that arterial application of the K+ channel blocker 4-aminopyridine (4AP) induces two different and independent seizure-like event (SLE) patterns in the olfactory and limbic regions (Carriero et al., 2010). We further characterize here the network and cellular features of SLEs in the olfactory cortices. Method: 4AP was arterially administered (50 lM; 5 min) or locally injected (2.5 mM) in the in vitro isolated guinea-pig brain. Field potentials (FPs) were simultaneously recorded from different limbic subregions. Simultaneous extracellular and intracellular recordings and [K+]o shifts were recorded to characterize the activity in PC. Result: We observed runs of fast activity (FRs) and SLEs featuring runs of high frequency activities superimposed to slow components followed
103 Abstracts
by a serie of spikes. Lesions and local 4AP applications demonstrated that SLEs initiate in PC. We found that layer II neurons discharged during FRs and that during SLE there was a progressive inactivation of firing that was blocked at the peak of the membrane depolarization and resumed during the spikes. The firing block was rescued injecting hyperpolarizing current, suggesting a depolarization block. We found the abolishment of the evoked response during SLEs after lateral olfactory tract stimulation and a partial recovery during the spikes. Simultaneous recordings of FPs and [K+]o shifts showed a gradual [K+]o increase during FRs and a secondary faster increase during SLEs. Synaptic activity recovers after synchronous spiking and levels of [K+]o recovered. Conclusion: The PC is the generator of the described activities. We observed a hypo-excitable status of PC networks that initiates a focal seizure-like discharge. intracerebroventricular des-acyl ghrelin administration affected food intake via the orexin pathway. Recently, des-acyl ghrelin has been proposed to have beneficial effects on limbic seizures. In this study, we further characterised the role of des-acyl ghrelin in seizures using the focal pilocarpine model for limbic seizures. Method: In this study we used the in vivo rat model for pilocarpineinduced limbic seizures. Intrahippocampal administration of des-acyl ghrelin, the dual orexin receptor antagonist almorexant, or co-administration of des-acyl ghrelin and almorexant was performed in rats for 2 h prior subsequent administration of pilocarpine directly in the hippocampus. Rats were monitored following pilocarpine perfusion, and seizure behavior grades were evaluated according to a modified Racine's scale. Result: We noted that while des-acyl ghrelin attenuated pilocarpineinduced limbic seizures at different concentrations, almorexant did not affect seizure severity. To determine whether des-acyl ghrelin utilizes the orexin pathway for its anticonvulsant effect, des-acyl ghrelin was coadministered with almorexant. Dual orexin receptor blockade did not prevent des-acyl ghrelin's anticonvulsant effect. Conclusion: We confirmed that des-acyl ghrelin attenuates limbic seizures and established that the orexin pathway is not involved. This is also first evidence that simultaneous antagonism of hippocampal orexin receptors does not affect seizure severity. This study highlights the need of identifying the mechanism of action of des-acyl ghrelin in epileptic seizures.
p351 HOW DO CHANGES IN GABAB RECEPTOR EXPRESSION AFFECT IDIOPATHIC GENERALISED EPILEPSY PHENOTYPES? (LITERATURE REVIEW) G. Summons Cardiff University, Maidenhead, UK
Purpose: GABA undergoes complex receptor modulations in epileptic tissue, forming inhibitory and excitatory networks. GABAB receptors (GABABRs) underlie various phenotypes of Idiopathic Generalized Epilepsy (IGE). Generally, GABAB agonists exacerbate absence seizures. GABAB antagonists reduce absences. Convulsive seizures may be induced by GABABR inhibition, and alleviated by GABAB agonists. GABABR isoforms B1a, B1b and B2 perform specific roles allowing normal GABABR functioning, hence directly impact IGE phenotypes. Controversially, atypical absence seizures have been observed in GABAB knockout models, implying a contradiction to prior research. Method: A metasearch was conducted to determine how altered GABABRs in rodent models produce different IGE phenotypes, producing 28 articles. Result: A minority of papers noted normal GABABR expression in typical absence seizures, contradicted by pharmacological studies where they were exacerbated by GABAB agonists. Other studies showed increased GABABR expression with age and seizure occurrence. This was attributed to increased neocortical GABAB autoreceptor expression and increased presynaptic GABAB thalamic expression. Transgenic upregulation of B1a and B1b induced atypical absence seizures in thalamocorticolimbic networks. Knockout studies in corticolimbic networks caused clonic seizures. Atypical absences were only observed in a minority of GABAB1-/- mice. Seizure severity is subtype specific; B1a rescued the clonic phenotype, and increased absence severity when upregulated. Conclusion: Absence seizures are predominantly caused by excess inhibition in thalamocortical networks, due to increased GABABRs expression; these seizures become atypical when GABABRs are upregulated in the limbic network. Clonic seizures are associated with reduced GABABR expression. Seizure severity is modulated by varying expression of GABAB subtypes.

p353 ANTI-SEIZURE ACTION OF THE ANTIDEPRESSANT, SERTRALINE M. Sitges, and B. I. Aldana Instituto de Investigaciones Biomdicas, Universidad Nacional Autnoma de Mxico, Mxico D.F., Mexico
Purpose: Investigate the potential anticonvulsive action of sertraline, as recently we found that sertraline inhibits cerebral presynaptic Na+ channels controlling release of the excitatory amino acid neurotransmitter glutamate (Aldana & Sitges J Neurochem 2012; in press); like several antiepileptic drugs do (Sitges M et al. Neuropharmacology 2007;52:598 605). Method: Pentilenetetrazole (PTZ, 50 mg/kg i.p.)-induced seizures and cortical excitability changes, as judged by the EEG highest peak amplitude value (HPAV), were respectively evaluated in non anesthetized and in anesthetized animals previously administered with: vehicle (control group), sertraline (range from 1.5 to 25 mg/kg) and carbamazepine (15 and 25 mg/kg), as positive control. Result: In all the non anesthetized animals injected with vehicle the first generalized tonic-clonic seizure was presented near the first minute following PTZ and 40% of the animals died. In animals administered with 2.5 mg/kg sertraline the latency of the first seizure to PTZ increased and its duration decreased but seizures were not prevented. At a high dose (25 mg/kg) sertraline completely prevented seizures to PTZ. None of the animals pre-administered with sertraline at any dose died. In the anesthetized animals injected with vehicle, the baseline EEG HPAV (42 1 lV) increased to 164 6 lV in the first 120 s interval following PTZ. This PTZ-induced increase in the HPAV was: insensitive to 15 mg/kg carbamazepine, lost in half of the animals injected with 2.5 mg/kg sertraline and absent in all the animals injected with sertraline above 5 mg/kg or with 25 mg/kg carbamazepine. None of the anesthetized animals died. Conclusion: Present findings demonstrate the anti-seizure effect of sertraline.
p352 THE OREXIN PATHWAY IS NOT INVOLVED IN THE ATTENUATION OF LIMBIC SEIZURES BY DES-ACYL GHRELIN J. Coppens, J. Portelli, Y. Michotte, and I. Smolders Vrije Universiteit Brussel, Brussels, Belgium
Purpose: Once considered inactive, des-acyl ghrelin is now implicated in a number of biological functions. Unlike ghrelin, des-acyl ghrelin is unable to activate the ghrelin receptor and recently one study implied that
104 Abstracts
p354 PROTEOMIC PROFILING OF THE HIPPOCAMPUS OF EPILEPTIC MICE WITH AND WITHOUT SCLEROSIS A. Mago*, K. A. Kekesi, A. Simor, K. Tth, E. HunyadiGulyas, Z. Darula, K. Medzihradszky, T. Freund*, G. Juhasz, and Z. Magloczky* *Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary; Etvs Lornd University, Inst. Biology, Budapest, Hungary; Institution of Experimental Medicine, HAS, Budapest, Hungary; Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary; and Etvs Lornd University, Inst. Biology, Research Group of Proteomics, Budapest, Hungary
Purpose: Abnormal expression of certain proteins was found in neurodegenerative diseases. We analyzed proteomic networks in the pilocarpine-model of epilepsy in mice. Method: After one-month survival the animals were sacrificed and the brain was removed. The right hippocampus was processed for proteomic analyses, the left one for morphological characterization. Proteins were separated by 2-dimensional gel electrophoresis, and identified by Liquid chromatography-mass spectrometry. Animals were classified on the basis of the hippocampal cell loss as non-sclerotic or sclerotic. Result: We examined the proteomic alterations compared sclerotic to control and non-sclerotic to sclerotic animals. A network was built from these proteins using Ariadne Genomics Pathway studio software establishing direct interactions of proteins, and their relationships with schizophrenia, Alzheimer's disease (AD), Parkinson's disease, temporal lobe epilepsy and anxiety. In the networks there were 54 out of 93 (in case of control-sclerotic) and 44 out of 82 (in case of non-sclerotic-sclerotic) proteins with at least one interaction with protein or disease. These proteins were analyzed by establishing three functional groups: metabolisms, synaptic and receptor functions and cytosceleton. Their contributions in epileptic reorganization are analyzed. Overlap with other neurological disorders was found. The altered proteins showed the most connection with AD and the least connection with anxiety. Conclusion: On the basis of the data, some neurological diseases may have overlapping molecular mechanisms. Furthermore, no direct interactions with proteins/diseases were found in the networks in case of certain proteins. It might mean that available data about the functions and interactions of proteins are incomplete in the scientific literature. iod). At the end of training period, convulsive dose of homocysteine thiolactone (8.0 mmol/kg) was intraperitoneally injected to rats from both groups and convulsive behavior was assessed by seizure incidence, latency to first seizure, number of seizure episodes and its severity (04 grades scale). Result: There were no statistically significant differences in seizure incidence induced by homocysteine thiolactone between exercised and sedentary rats (p > 0.05). Latency to first seizure was increased in exercised comparing to sedentary group of rats. Exercised rats displayed lower number of seizure episodes per rat in comparison with sedentary rats (p < 0.05), but severity of these seizures did not differ significantly between groups. Conclusion: These results indicate beneficial effects of chronic aerobic exercise in model of homocysteine thiolactone-induced seizures in rats, supporting the promotion of sport and physical exercise among patients with epilepsy.
p356 EARLY AND LATE MRI CHANGES IN RAT BRAIN AFTER STATUS EPILEPTICUS AND BEHAVIORAL IMPAIRMENT E. Suleymanova*, M. Gulyaev, A. Barkova, and N. Chepurnova *Lomonosov Moscow State University, Faculty of Biology, Moscow, Russian Federation; Lomonosov Moscow State University, Moscow, Russian Federation; and Lomonosov Moscow State University, Biological faculty, Moscow, Russian Federation
Purpose: Status epilepticus is a dangerous condition which can lead to brain damage and impairment of memory and cognitive functions later in life. The purpose of our study was to investigate the relationship between acute damage caused by prolonged seizures and later consequences of status epilepticus. Method: The lithium-pilocarpine model of status epilepticus (SE) in rats was used. MRI study of rat brain was performed 2, 7 and 30 days after SE. High-resolution T2 images and T2-maps were obtained, and total damaged area, hippocampal volume, and T2 relaxation time in several brain structures were calculated. After the MRI study, animals were tested in an open field. The test was performed three times with 24-hour intervals. To study depression-like behavior in rats, forced swim test and taste preference test were performed to evaluate depression. Result: Two days after SE, an increase of T2 signal was found in hippocampus and associated structures. The patterns of brain damage in rats after SE varied considerably. All rats after SE demonstrated hyperactivity in an open field one month later and did not habituate. These rats also were more active in the forced swim test, however some animals demonstrated the lack of taste preference. Rats with considerable acute changes in brain, tended to demonstrate higher activity in an open field in comparison with rats with less pronounced early MRI changes and were more prone to anhedonia. Conclusion: Rats with severe MRI abnormalities in brain found two days after SE tend to develop more pronounced behavioral impairment 1 month later.
p355 BENEFITS OF AEROBIC EXERCISE FOR ADULT RATS WITH SEIZURES INDUCED BY HOMOCYSTEINE THIOLACTONE D. Hrncic*, A. Rasic-Markovic*, R. Sarhan, V. Susic, D. Macut*, D. Djuric*, and O. Stanojlovic* *Belgrade University School of Medicine, Belgrade, Serbia; Menoufia University Faculty of Medicine, Tanta, Egypt; and Serbian Academy of Sciences and Arts, Belgrade, Serbia
Purpose: Homocysteine, together with its reactive thioester homocysteine thiolactone is proven risk factor for numerous CNS disorders including epilepsy. The aim of this study was to determine the effects of chronic aerobic exercise on rat model of homocysteine thiolactone induced seizures. Method: Adult male Wistar rats were familiarized with the treadmill apparatus (NeuroSciLaBG-Treadmill, Elunit, Serbia) for 3 days in sessions of 10 min at ramp belt velocity of 510 m/min. Afterwards, rats were randomly divided into 2 groups: chronic aerobic exercise (30 min treadmill training at 20 m/min velocity for 30 days) and sedentary control (the same time spent in treadmill apparatus at 0 m/min for the same perEpilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x
p357 BRIEF SEIZURES INDUCE A SEVERE ISCHEMIC/HYPOXIC EPISODE G. C. Teskey, and J. S. Farrell University of Calgary, Calgary, Canada
Purpose: Ischemic/hypoxic episodes and seizures both result in a number of deleterious effects to brain functioning including enhanced
105 Abstracts
inflammatory responses, blood brain barrier permeability, astrocyte activation and neuronal death. This suggested to us that seizures may result in an ischemic/hypoxic episode. We tested this hypothesis by measuring local brain oxygen levels, before during and after brief seizures in a number of forebrain structures. Method: Adults rats had both an electrode and an oxygen sensing optrode implanted in their motor neocortex, amygdala or hippocampus. One week after implantation surgery, oxygen levels were recorded in awake, freely moving rats during and following electrically elicited seizures or other types of patterned electrical stimulation that did not result in seizures. Result: Immediately following termination of the afterdischarges we observed a severe hypoxic episode (<10 mm pO2) that lasted on the order of tens of minutes in the neocortex and an hour in the hippocampus. Electrical stimulation that did not give rise to a seizure did not result in a hypoxic episode. Pharmacological agents that did not affect the seizure but enhanced vasodilation and blocked vasoconstriction prevented the seizure-induced severe ischemic/hypoxic episode (SISIHE). Conclusion: Seizures result in vasoconstriction that leads to reduced local blood flow and severely reduced oxygen levels. It is possible that it is not the seizures per se that directly cause the long-term disruption of brain function, but the resulting ischemic/hypoxic episode. This phenomenon has potentially important implications for the management of seizure disorders. Purpose: Oxidative stress is known to decrease convulsion threshold and depletion of endogenous antioxidants was suggested to provide a molecular mechanism that triggers ictogenesis in a genetic mouse model for secondary generalized seizures (Takaki et al. Brain Res 2008;1228:15). We therefore investigated total glutathione (GSH) content in somatosensory cortex (SSC) of pre- and symptomatic WAG/Rij rats, a well-validated model for absence seizures. Moreover, protein expression levels of xCT (specific subunit of the cystine/glutamate antiporter) as well as EAAC1 were measured in these rats. These transporters provide respectively glial cells and neurons with cyst(e)ine, the rate-limiting building block in the synthesis of GSH. Method: Semi-quantitative western blotting was performed on SSC tissue of respectively presymptomatic and symptomatic WAG/Rij animals and age-matched ACI control rats using rabbit EAAC1 antibody (1:4000; Alpha Diagnostic) and rabbit xCT antibody (1:10000; Massie et al. Neuroreport 2008;19:15891592.). Total GSH content was examined using a Quant-iT Protein Assay Kit (Invitrogen). Result: A significantly decreased expression of xCT (ACI 100,0 5,8%; WAG/Rij 73,5 5,8%; p = 0,03) and EAAC1 (ACI 100,0 15,1%; WAG/Rij 53,7 2,5%; p = 0,002) was observed in the young WAG/Rij rats. In the symptomatic WAG/Rij rats, protein levels of xCT (ACI 83,9 2,0%; WAG/Rij 161,4 28,9%; p = 0,002) were significantly increased compared to the age-matched ACI rats. Total GSH content was unaffected in presymptomatic WAG/Rij rats. Conclusion: Although expression levels of xCT and EAAC1 were altered in SSC samples of both presymptomatic and symptomatic WAG/Rij rats, total GSH content was unaffected compared to ACI control rats.
p358 THE DYNAMICS OF CORTICO-THALAMO-CORTICAL NETWORK INTERACTIONS AT THE TRANSITION TO SPIKE-WAVE DISCHARGES G. Van Luijtelaar, and A. Luttjohann Radboud University Nijmegen, Nijmegen, The Netherlands
Purpose: Generalized absence seizures are generated within the corticothalamo-cortical system. We analysed thalamic and cortical-thalamic interactions via multisite local-field-potentials with the aid of non-linear association analyses. Method: WAG/Rij rats with multiple electrodes targeting subgranular layers of the somatosensory-cortex, rostral and caudal RTN, VPM, anterior-(ATN) and posterior (Po) thalamic nucleus were used. Dynamics of association strength, coupling-direction and time-delays between all channel pairs were analyzed pre-ictally, ictally and in control periods. Result: Earliest and strongest increases in coupling-strength were seen between cortical layer 5/6 and Po. Other thalamic nuclei became involved later in SWD activity. The cortex guided most thalamic nuclei while cortex and Po kept a bidirectional crosstalk during the first 500 ms of SWDs. Most thalamic nuclei guided the Po until the end of the SWD. While the rostral RTN showed increased coupling with Po, the caudal RTN decoupled. Instead, it directed its activity to the rostral RTN. Conclusion: Next to the focal cortical instignation zone of SWDs, the Po seems crucial for their occurrence. This nucleus shows early increases in coupling and is the only nucleus which responds to the cortex within the first 500 ms of SWDs. Other thalamic nuclei seem to have only a function in SWD maintenance. Rostral and caudal-RTN have opposite roles in the occurrence of SWD.
p360 EVALUATION OF NOVEL BEHAVIOURAL CORRELATES TO ELECTROGRAPHIC SEIZURE ACTIVITY IN MICE J. Zelano, and K. Kullander Uppsala University, Uppsala, Sweden
Purpose: Epileptic vulnerability in rodents is frequently evaluated by observing the effects of a seizure-inducing insult, such as pilocarpine injection. However, seizure scoring is difficult, user dependent, and requires an elaborate setup. Lately, several new simplified ways of grading seizure response have emerged in the litterature. The correlation between these behavioural observations and EEG-verified seizure activity has not been investigated. This pilot study aimed to use video-EEG to evaluate novel simplified behavioural seizure correlates such as latency to grade 56 seizure, number of grade 56 seizures, or seizure index (an arbitrary grouping of high-grade seizures), in the pilocarpine-induced status epilepticus model in mice. Method: Video-EEG was performed on mice from the 129-strain, which is commonly used for genetic modification. Pilocarpine was administered as a single peritoneal injection and the animals were observed for 90 minutes. EEG and video was then interpreted separately and statistical correlation sought between behavioural correlates and EEG seizure activity. Result: Similar number of grade 56 seizures were observed in mice with very different duration of electrographic seizure activity. Latency to the first grade 56 seizure correlated best with duration of EEG seizure activity, but did not reach statistical significance. Conclusion: Some of the novel behavioral correlates may not be optimal surrogate markers for electrographic seizure activity, indicating that EEG should ideally be performed when screening transgenic mice in this model. We plan a larger study to asess which behavioural correlate is best to use in the absence of EEG.
p359 AGE-DEPENDENT CHANGES IN XCT AND EAAC1 EXPRESSION IN SOMATOSENSORY CORTEX OF WAG/RIJ RATS J. Van Liefferinge*, A. Schallier*, G. Van Luijtelaar, Y. Michotte*, A. Massie*, and I. Smolders* *Vrije Universiteit Brussel, Brussels, Belgium; and Radboud University Nijmegen, Nijmegen, Netherlands
106 Abstracts
p361 EFFECT OF LOW-FREQUENCY STIMULATION ON THE AFTERDISCHARGE INDUCED BY ACUTE KINDLING OF THE RABBIT HIPPOCAMPUS K. Tsuchiya, S. Kogure, A. Kusahara, and T. Iwata Soka University, Hachioji, Tokyo, Japan
Purpose: We have performed fast Fourier transformation (FFT) analysis on the afterdischarge (AD) induced by chronic hippocampal kindling of the rabbit and revealed that enhancement of the higher frequency band (HFB: 1230 Hz) component is associated with kindled stage. In the present study, we examined effect of low-frequency stimulation (LFS) on ADs induced by acute kindling of the rabbit hippocampus to reveal the underlying mechanism of anti-kindling effect of LFS. Method: Fourteen adult rabbits were used. Under deeply anesthesia, kindling stimulations (1 msec, biphasic 50 Hz, 1 sec train) with suprathreshold intensity for AD were delivered at 20-min intervals to the right hippocampus. The LFS was added at 1 Hz for 15 min immediately or 20 sec after the kindling stimulation to the ipsilateral or contralateral side when HFB in AD increased to the kindled level. FFT analysis on each AD was performed to reveal the LFS effect. Result: During the acute kindling, the power spectral density (PSD) ratio of HFB component against total PSD changed from 16.1 9.7% (meanSD) at the initial stage to 45.9 17.6% (p < 0.001) at the final stage. Both types of LFS application could not suppress the enhancement of HFB component, but suppress the appearance of kindling-induced spontaneous seizure activity. Conclusions: An enhancement of HFB component also occurred in the acute kindling. Anti-kindling effect of LFS may depend on stimulation site and timing. multilobar, 2(5%) hemispheric and 5(12%) bilateral. Favorable seizure outcomes were achieved in 6/6 (100%) patients with completely resected, 8/23(35%) with partially resected, 5/7(71.5%) with non-resected hyperperfusion zone and in 1/8(12.5%) subjects with no ictal SPECT activation. Conclusion: Complete resection of the ictal SPECT hyperperfusion zone is a strong predictor of surgical success in children with TSC. Epilepsy surgery planning in TSC is nevertheless highly complex; SPECT findings should be correlated with clinical, electrophysiological and other neuroimaging data. Supported by Kontakt Program ME09042, IGA NT/11443-5, CZ.2.16/3.1.00/24022 and GAUK 17010.
p363 EFFICACY OF VAGUS NERVE STIMULATION IN 28 CONSECUTIVE PATIENTS WITH TREATMENT RESISTANT EPILEPSY NOT ELIGIBLE FOR EPILEPSY SURGERY F. Dainese*, G. Randazzo, G. Pauletto, F. Paladin*, C. Lettieri, C. Conti, M. Skrap, L. Comelli, A. Volzone, and P. Bonanni *SS Giovanni e Paolo Hospital, Venice, Italy; IRCCS Eugenio Medea, Conegliano (TV), Italy; SM della Misericordia Hospital, Udine, Italy; and DellAngelo Hospital, Mestre (VE), Italy
Purpose: The aim of this study was to assess the efficacy and safety of vagus nerve stimulation (VNS) in a consecutive series of patients with refractory epilepsy (RE) not eligible for epilepsy surgery. Method: This is a retrospective study of 28 patients who underwent VNS implantation for RE between 1996 and 2011. Patients were recruited from 3 epilepsy units in the North-East of Italy. The age at time of implantation was from 8 to 59 years (mean age 32,34; SD 12,7 y). All patients were classified according to the epileptic phenotype and the etiology. Twenty-one patients had focal or multifocal epilepsy, of whom 7 with bitemporal epilepsy, 4 had Lennox-Gastaut syndrome, 2 had Dravet syndrome, 1 had Angelman syndrome. According to the last proposal of classification, the etiology was structural in 16 patients, genetic in 3 and unknown in 9. All patients had a long duration of epilepsy before implantation (mean age 24 y). Result: Duration of VNS treatment varied from 0 to 15 years (mean 3 y). Mean seizure frequency significantly improved following implantation in 64% of patients. Interestingly 56% of patients showed also improvement in quality of life. No important side effects were reported by patients. Conclusion: VNS is a safe and effective palliative treatment option for RE not eligible for epilepsy surgery. Interestingly our data show that VNS is an effective treatment not only in cases of epilepsy with structural or unknown etiology but also in case of epilepsy due to a specific genetic cause as Dravet Syndrome and Angelman Syndrome.
Epilepsy Surgery 3 Tuesday, 02 October 2012

p362 LOCALIZING VALUE OF ICTAL SPECT IN PATIENTS WITH TUBEROUS SCLEROSIS COMPLEX AND INTRACTABLE EPILEPSY A. Jahodova*, M. Kudr*, P. Krsek*, V. Komarek*, P. Jayakar, C. Dunoyer, T. Resnick, and M. Duchowny *University Hospital Motol, Prague, Czech Republic; and Brain Institute, Miami children hospital, Miami, FL, USA
Purpose: To assess a practical value of ictal SPECT in localizing the seizure onset zone in pediatric patients with tuberous sclerosis complex (TSC) and intractable epilepsy. Method: We visually evaluated 52 ictal SPECT studies in 26 children with TSC surgically treated in Miami Children's Hospital between 1994 and 2010. The extent and location of the ictal hyperperfusion was evaluated and completeness of its surgical removal was assessed. The extent of the hyperperfusion zone resection was classified as completely resected, partially resected and non-resected and correlated with postsurgical seizure outcomes. Outcomes were regarded as favourable in patients with 90% seizure reduction and unfavourable in subjects with <90% seizure reduction. Result: There were 35 studies in previously non-operated patients, nine postsurgical studies in patients who subsequently underwent a reoperation and eight postsurgical studies in patients who had no further surgery (excluded from outcome analyses). Cortical hyperperfusion was present in 41(79%) ictal studies and absent in 11(21%) studies. In 41 positive SPECT studies, 10(24%) were well-localized, 13(32%) lobar, 11(27%)
p364 RESECTIVE SURGERY FOR REFRACTORY STRUCTURAL EPILEPSY IN INFANTS AND YOUNG CHILDREN G. Ramantani*, N. E. Fritz, K. Strobl, G. Wiegand, S. Schubert-Bast, H. Mayer, R. Korinthenberg*, U. Stephani, J. Zentner*, A. Schulze-Bonhage*, and T. Bast *University Hospital Freiburg, Freiburg, Germany; University Childrens Hospital, Heidelberg, Germany; Epilepsy Center Kork, Kehl-Kork, Germany; and University Medical Centre Schleswig-Holstein, Kiel, Germany
107 Abstracts
Purpose: Resective surgery is becoming an important treatment option for refractory structural epilepsy in early childhood. We report on indications, complications and outcomes in very young children undergoing epilepsy surgery at the Epilepsy Centre Freiburg. Method: We retrospectively reviewed the electroclinical, neuroimaging and neurodevelopmental findings, surgical procedures and complications, histologically defined epilepsy substrates and outcomes of children under 3 years of age that underwent epilepsy surgery in the years 2001 2011. Result: 30 children were included in this study. Seizure onset was in the first year of life in 28 (93%) patients and mean age at first surgery was 20.6 months (533.6 months). 18 (60%) infants had a historyof infantile spasms. Epilepsy substrates consisted in malformations of cortical development in 24 (80%) cases, glioneural tumor alone or in combination with cortical dysplasia in 3 (10%), and infarct in 3 (10%). 34 surgical procedures were performed including 16 (47%) functional hemispherectomies, 7 (21%) multilobar resections and 11 (32%) intralobar resections. 3 children underwent repeat surgery in our institution, while a single child had three consecutive resections. No mortalities occurred. Surgical complications included hydrocephalus in 3 patients as well as meningitis and hemorrhage in single cases. In follow-up from 1 to 11 years, seizure freedom was achieved in 23 (77%) children (Engel I), while 5 (17%) demonstrated a worthwhile improvement (Engel II or III) and 2 (7%) children showed no remarkable improvement. Developmental outcomes were generally preserved. Conclusion: Benefit in terms of seizure control and developmental progress is achievable in the majority of very young children with structural epilepsy selected for resective surgery. While early complication rates are infrequent and manageable, late complications are limited to extensive, hemispheric procedures. Cognitive outcomes were not compromised in the majority of our cohort. Conclusion: Lesional TLE in young children may present as a catastrophic epilepsy. Although with generalized clinical and electrographic features, a resective epilepsy surgery should be considered as early as possible to achieve seizure control and improvement of mental development.
p366 LONG-TERM OUTCOME OF RESECTIVE SURGICAL PROCEDURES IN ADULT PATIENTS WITH REFRACTORY EPILEPSY-THE KORK SERIES A. M. Staack*, A. Wendling*, I. Wisniewski*, J. Scholly*, S. Bilic*, C. Kurth*, U. Kraus*, J. Saar*, B. Oehl, D. Altenmller, T. M. Freiman, A. Schulze-Bonhage, J. Zentner, G. Reinshagen*, and B. J. Steinhoff* *Kork Epilepsy Centre, Kork, Germany; and Epilepsy Centre, University of Freiburg, Freiburg, Germany
Purpose: Epilepsy surgery is an established treatment option for a well defined and pre-selected group of patients with drug-resistant epilepsy. The long-term follow-up is important to identify predictive factors for a favourable outcome. Method: We collected data for 340 adult patients from the Kork Epilepsy Centre who had undergone surgery for drug-resistant epilepsy. We used a standardized questionnaire to obtain updated information about postsurgical outcome and classified seizure outcome according to the ILAE surgery outcome scale (OC 1 OC 6). Result: In total 211 (62%) patients have been completely seizure free (OC1), 228 (67%) patients have remained seizure free, apart from simple partial seizures (OC2) at the time of the most recent evaluation. Mean post-operative follow-up time was 6.7 years (range 1.021.6 years). A running-down phenomenon (initially seizures and finally complete remission) has been seen in 38 (11.2%) patients. The majority of patients (266; 78.2%) underwent temporal lobe resections. 64% of the temporal resected patients and 52% of the patients with extra-temporal resections became seizure-free (OC1). Only 38% of the patients with negative MRI achieved complete seizure-freedom (OC1). Conclusion: With 62% (OC1) to 67% (OC2) seizure-free patients, our study shows satisfying long-term outcome results over more than six years. In our study, best results were seen in lesional temporal lobe epilepsy, whereas MRI-negative epilepsy was associated with a less favourable outcome in line with the literature.
p365 CLINICAL FEATURES OF SEIZURES SEMIOLOGY AND ELECTROENCEPHALOGRAPHY IN YOUNG CHILDREN WITH LESIONAL TEMPORAL LOBE EPILEPSY X. Shao, and Z. Sun Beijing Tiantan Hospital Affiliated to Capital Medical University, Beijing, China
Purpose: This study is to discuss the features of seizure semiolgy and electroencephalography(EEG) in young children with lesional temporal lobe epilepsy. Method: 11 children with temporal lobe lesions were received presurgical evaluation for intractable epilepsy. The age of seizure onset was under 3 years. All patients were seizure-free after temporal lobectomy with more than 1 year follow-up. We reviewed medical history and videoEEG monitoring to analyze semiology of seizures and EEG findings and compared to that of adult TLE. Result: All patients have daily seizures although with anti-epileptic drugs (AEDs). 84 seizures were recorded and analyzed in 11 children (aged from 23 months to 108 months; mean 50.5 months). The age of seizure onset was from 1 month to 26 months (mean; 17.6 months). All patients exhibited prominent motor manifestations, including epileptic spasm, tonic seizure(symmtric or asymmtric) and unilateral clonic seizure. seven children manifested behavioral arrest similar to automotor seizures in adult TLE, but with shorter duration and more frequency. Automatisms were mostly orofacial and mannual automatism is rarely observed. EEG recording revealed that generalized discharges patterns were more common in younger children while focal or unilateral patterns usually in older children. All children have mental development delay or regression but with significant improvement after surgery, especially with early operation.
p367 RISK FACTORS FOR EPILEPTIC SEIZURE OF CAVERNOUS MALFORMATIONS IN THE CENTRAL NERVOUS SYSTEM: 52 CASES C. Huang*, J. Li, and D. Zhou *Sichuan University, Chengdu, China; and West China Hospital, Chengdu, China
Purpose: To determine the risk factors for preoperative and postoperative epileptic seizure in patients with cavernous malformations (CMs). Method: We retrospective studied 52 consecutive patients diagnosed with CMs who were surgically treated and histopathologically confirmed in West China Hospital of Sichuan University from January 2009 to June 2001. Clinical data, treatment procedure and follow-up information were collected. Result: In the univariate analysis, factors associated with preoperative epileptic seizure were low birth weight (p = 0.017), temporal lobe involvement (p = 0.003) and cortical lesion (p = 0.025). In the multivariEpilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x
108 Abstracts
ate analysis, the cortical lesion showed a high risk for preoperative epileptic seizure (OR=10.48; 95% CI 1.6168.23). In the univariate analysis, patients with temporal lobe CMs were found more likely to be seizure free after surgery (p = 0.016). The maximum diameter of CMs longer than 2.5 cm (p = 0.012) and disease course longer than 1 year (p = 0.050)predicates an unfavorable outcome. In the multivariate analysis, temporal lobe involvement still showed a favorable outcome (OR=0.038; 95% CI 0.0020.833). Application of ECoG did not make significant difference to seizure outcome (p = 0.430). Conclusion: Surgical treatment of patient with CMs is satisfactory in most cases and temporal lobe involvement usually predict favorable postoperative seizure outcome whether under the monitoring of ECoG or not. Thus, epileptic patients with CMs should be considered for surgical treatment especially when cortical brain layer or temporal lobe was involved. All clinical notes were reviewed in order to evaluate the age at onset, the seizure type at onset and during the follow-up, treatment and epilepsy outcome. HH were defined according to the classification proposed by Delalande et al (Delalande et al., 2003). In 4 out of 17 studied patients an intraoperative endoscopic intralesional recording was performed. In 3 cases intraoperative stereo-EEG was carried out using foramen ovale electrodes (Dixi Medical ACS798S, 5 contacts), and DBS leads in 1 case (Medtronic 3389, 4 contacts). Scalp-EEG was performed in all patients (referential montage, lacking frontal and central leads for surgical reasons). Result: In 10 out of 17 cases a surgical approach was performed: 4 of them underwent a one stage stereo-endoscopic disconnection, 3 cases a double stage stereo-endoscopic disconnection, and 1 case required a multistage stage stereo-endoscopic disconnection. One patient performed a bilateral deep brain stimulation (DBS) protocol, 1 a surgical resection, 1 radiotherapy, and 1 radiosurgery. Following Delalande classification HH were mostly of type 2 (8 out of 17), followed by type 3 (6 out of 17) and lastly type 4 (3 out of 17). No cases were classified as type 1. Data on intraoperative stereo-EEGAll patients (4 cases) presented gelastic seizures, associated to focal with secondarily generalization. Seizures frequency ranged from multiple per day to multiple per week. Seizure duration was between few seconds to 60 seconds. Following Delalande classification 2 patients had type 2 HH and other two had type 4 HH. Interictal scalp EEG showed epileptiform abnormalities in all patients, in 2 cases they were evident on temporal region, in one over bilateral parieto occipital, and in one over central and parietal regions. In all patients intraoperative scalp-EEG showed synchronous interictal epileptic discharges which were recorded from the same side of the lesion. From the depth electrode high amplitude fast activity in sequences of variable duration was recorded. In all cases the predominant side of the EEG abnormalities was ipsilateral to the activity recorded within the hamartoma. Conclusion: We detected the electrical activity of the lesion, and compared it with the scalp-EEG activity recorded in the same time. Our data confirm the epileptogenicity of HH. Clinical and neurophysiological findings in all described cases suggest that the cortical activation is secondary to the epileptogenic activity of HH. Intraoperative electrographic recording may be considered as part of a strategy of trans-endoscopic surgery for HHs.
p368 SHORT-TERM RESULTS OF STEREOTACTIC ANTERIOR CALLOSOTOMY IN THE TREATMENT DRUG RESISTANT EPILEPSY K. Kostiantyn, V. Tsymbaliuk, Y. Medvedev, Y. Zinkevich, A. Popov, S. Dichko, and O. Kanaykin Institute of Neurosurgery, Kyiv, Ukraine
Purpose: The purpose of study is to evaluate seizure outcome in patients with intractable primary and secondarily generalized epilepsy who underwent stereotactic anterior corpus callosotomy. Method: Eight patients aged 428 years with drug-resistant epilepsy underwent stereotactic anterior callosotomy, among them were 6 children. 5 pts had daily seizures and all 8 pts had episodes of status epilepticus in their history. 4 pts had partial seizures with secondarily generalization and one patient had primary generalized seizures. 7 pts had symptomatic epilepsy and 1 pt cryptogenic. Result: In postoperative follow up 4 22 months (mean 12 months) 1 pt became seizure free, in 4 cases achieved 90% and in other 3 cases 50% or greater seizures reduction respectively. In1 case seizure frequency did not change significantly. There were no postoperative complications in our series. Conclusion: Our short-term study confirms that stereotactic anterior callosotomy is a safe palliative surgical procedure that is suitable for some patients with drug-resistant epilepsy, suffering from primary or secondarily generalized seizures who are not candidates for focal resective surgery.
p369 ACUTE INTRALESIONAL RECORDING IN HYPOTHALAMIC HAMARTOMAS: DESCRIPTION OF 4 CASES N. Specchio*, M. Rizzi, L. Fusco*, A. Medda*, S. Cappelletti*, C. Marras*, F. Vigevano*, and O. Delalande* *Bambino Ges Children's Hospital, Rome, Italy; and Neurological Institute C. Besta, Milan, Italy
Purpose: To report the results of acute intralesional recording of the interictal activity arising inside the Hypothalamic hamartomas (HH) in 4 cases and to compare it with concurrent scalp EEG. Method: We have reviewed the medical records of 17 children affected by drug resistant focal epilepsy associated to HH, referred between January 1990 and December 2011 to the Neurology Division of the Bambino Ges Children's Hospital in Rome, and Carlo Besta Neurological Institute in Milan.
p370 VAGUS NERVE STIMULATION DECREASE EMERGENCY ASSISTANCE AND HOSPITALIZATION IN DRUG-RESSISTANT EPILEPTIC PATIENS T. Garca-Sobrino, X. Rodrguez-Osorio, A. Lpez-Ferreiro, M. Santamara-Cadavid, E. Corredera, A. Prieto, M. Peleteiro, and F. J. Lpez-Gonzlez Complejo Hospital Clnico Universitario de Santiago de Compostela, Santiago de Compostela, Spain
Purpose: VNS is an effective method to reduce seizure frequency in refractory epilepsy when resective surgery is ruled out. We aim to study efficacy and need of medical resources after VNS implantation in relation with the preimplantation period. Method: Restrospective study of patients with VNS implantation (20022011) with 1 year of follow-up. Response to VNS was achieved after 50% of reduction of seizures. We analyzed demographic data, efficacy, emergency assistance, hospitalization days in relation with epilepsy and outpatient follow-up after one, two and three years postimplantation, compared with 1 previous year period. Result: Thirthy-nine patients (57.5% females) with a median age of 41 [31,52] years old were studied. Median frequency of seizures per month was 25 [6.25,144.5], with a time of evolution of epilepsy of 26 [18,37]
109 Abstracts
years. Response to VNS after 1, 2 and 3 years was achieved in 47.37% (n = 39), 51.6% (n = 38) and 54.84% (n = 32) of patients. After VNS, median emergency assistance due to epilepsy was 0[0,0], 0[0,1] and 0[0,0.5], reduced in comparison with the preimplantation period 1 [0,1] (p = 0.002; p = 0.027; p = 0.062), with a median of hospitalization days of 0[0,0] at 1, 2 and 3 years, compared to pre-VNS period 0 [0,2] (p = 0.025; p = 0.007; p = 0.05). However, attendance to the epilepsy clinic did not show significant reduction after VNS implantation with a median of 4[2,7], 5[3,7] and 4[3,5] annual visits compared to the year before VNS 5 [4,6] (p = 0.108; p = 0.462; p = 0.085). Conclusion: VNS is effective and reduces the need for emergency assistance and days of hospitalization in refractory epileptic patients.
*UK ILAE Chapter, London, UK; and Societyof British Neurological Surgeons, London, UK
Purpose: Epilepsy surgery is increasingly recognised as an important modality of treatment for people with epilepsy and particularly for people with medically refractory epilepsy. The last assessment of adult epilepsy surgery services was completed in 20001. We sought to provide an up to date picture of the state of adult and paediatric epilepsy surgical services in the UK. Method: We obtained a list of SBNS representatives in all UK Neurosurgical units. We wrote to the relevant consultants in the (17) identified epilepsy surgery centres across the country asking them to prospectively complete a questionnaire detailing all epilepsy surgery carried out at their centre between April 2010 and March 2011. The response rate was 100%. Result: In total there were 874 procedures (excluding invasive electrode recording) with the common resective procedure being temporal lobe surgery for hippocampal sclerosis (142 in adults, 13 in children). In contrast extra-temporal lesionectomies were far less common (78 adults, 18 adults) while non-lesional extra-temporal lobe procedures were rare (24 adults, 2 children). VNS implantation was carried in 401 people (276 adults). Conclusion: In comparison to the figures from ten years ago, there is no evidence that the number of adult temporal lobe resections carried out has significantly changed in the intervening years. VNS implantation is the most commonly performed procedure in both adults and children with the numbers carried out in adults increasing. These figures suggest that epilepsy surgery remains an under utilised service with a large number of people with refractory epilepsy not treated surgically.
p371 EVOLUTION UP TO 18 YEARS AFTER SURGERY FOR TEMPORAL EPILEPSY WITH HIPPOCAMPAL SCLEROSIS: IMPACT OF TECHNIQUE, MEDICATION MANAGEMENT AND PRESURGICAL VARIABLES D. Crestani*, M. Hemb*, R. F. Severino, A. Palmini*, E. Paglioli*, E. Paglioli*, J. Costa Da Costa*, M. Portuguez*, N. Azambuja*, and M. Nunes* *Hospital Sao Lucas, Porto Alegre, Brazil; and Sao Lucas Hospital, Porto Alegre, Brazil
Purpose: The chances of remaining seizure free for long periods are still unclear for patients undergoing surgery for mesial temporal lobe epilepsy and unilateral hippocampal sclerosis (MTLE/HS). Likewise, the impact of practical variables such as surgical technique and post-operative reduction of medication needs clarification. Method: We followed 108 patients with unilateral MTLE/HS for 8 to 18 years and generated Kaplan-Maier survival curves for the probability of remaining seizure free and for the modulating effect of medicaton and surgical technique. Univariate and multivariate regression analyses were perfomed to determine the impact of these and other variables. Result: A history of generalized tonic clonic seizures (GTCS) was present in 10% of the patients and only 16% needed intracranial EEG. The probability of remaining completely seizure-free at 12 and 18 years was 65% and 62%. 75% of patients have discontinued or significantly reduced antiepileptic drugs (AEDs). The type of surgical technique did not impact. Multivariate analysis showed that both a history of GTCS and remaining on full or almost full doses of AEDs significantly diminished the probability of remaining seizure free (Cox regression: p = 0.003 CI: 1.8422.41 for GTCS; p = 0.048, CI: 0.075.27 for AED management). Conclusion: Patient selection may be the most important determinant of remaining seizure free over the years. When the epileptologic profile indicates more restricted disease, removal of neocortical structures does not lead to better chances of seizure control and the reduction or discontinuation of AED does not prevent favorable results.
p373 LONG-TERM OUTCOME OF FUNCTIONAL TEMPORAL LOBE DISCONNECTION FOR NON-LESIONAL MESIOTEMPORAL EPILEPSY B. Legros, N. Massager, P. Tugendhaft, C. Depondt, T. Coppens, L. Drogba, N. Benmebarek, O. De Witte, and P. Van Bogaert ULB-Hpital Erasme, Brussels, Belgium
Purpose: In refractory mesial temporal lobe epilepsy (MTLE), surgical treatment is used to obtain seizure freedom, generally through the anatomical removal of the mesial structures. We developed a technique of functional disconnection of the temporal lobe (TLD). Here, we present long-term seizure outcome and complications of TLD in MTLE. Method: Data of 45 patients operated on for intractable MTLE using TLD were studied. Indication for TLD surgery was retained after a standard preoperative evaluation of refractory epilepsy and using the same criteria as for standard MTLE resection surgery. The epilepsy outcome of 41 patients with minimum 1-year follow-up was analyzed. Morbidity outcome was assessed on the whole population. Result: Mean follow-up duration was 3.48 y (range 19.5 y). At last follow-up 27 patients (66%) were completely seizure-free. Actuarial outcome display a probability of being seizure-free after 5 years of 67.3% and after 9.5 years, of 44.9%. No patient died after surgery and no subdural hematoma or hygroma occurred. Neurological impairment after surgery included speech fluency deficit, hemiparesis, hemianopsia and oculomotor nerve palsy. Permanent hemiparesis occurred in 3 patients, hemianopsia in 5 patients and oculomotor paresis in 1 patient. Conclusion: TLD is a valuable surgical technique for patients with intractable MTLE. The morbidity and long-term seizure outcome of TLD are similar to standard surgical removal techniques. This functional surgery could be an interesting alternative to resection that can reduce operating time and risks for subdural collections after surgery.
Epilepsy Surgery 4 Tuesday, 02 October 2012

p372 EPILEPSY SURGERY IN THE UNITED KINGDOM IN 2011, AN UPDATE A. Neligan*, J. K. Solomon*, B. Pettorini, and W. F. Harkness
110 Abstracts
p374 INFANTILE SPASMS AS THE UNIQUE SEIZURE TYPE IN HEMISPHERIC EPILEPSIES RELATED TO PERINATAL MIDDLE CEREBRAL ARTERY STROKE OUTCOME FOLLOWING HEMISPHEROTOMY C. Bulteau, D. Taussig, M. Chipaux, M. Fohlen, G. Dorfmuller, S. Ferrand-Sorbets, and O. Delalande Fondation Rothschild, Paris, France
Purpose: Infantile spasms (IS) are specific of severe early epileptic encephalopathy. They can be the unique ictal manifestation in patients with early ischemic lesions. Method: We present 3 patients out of our series of 215 hemispherotomies performed between 1990 and 2009, who presented with IS without focal seizures related to perinatal stroke in the distribution of the middle cerebral artery. Interictal as well as ictal video-EEGs were retrospectively studied. We considered postoperative follow-up. Result: Seizure onset was between 5 and 7 months of age. Mean age at the time of EEG-video recording was 22 months, and 27 months at the time of surgery. All patients had hemiparesis; a psychomotor regression occurred after onset of the IS. Interictal EEG favoured unilateral epilepsy with lack of physiological activity over the damaged hemisphere and multifocal sharp waves, whereas physiological activity was recorded over the safe hemisphere. In two cases, sharp waves were also recorded synchronously over both hemispheres. During the spasms, asymmetry was clinically and/or electrically obvious. No other seizure type was disclosed. Follow-up ranged between 26 and 144 months; all three patients are seizure-free without medication. The two patients who underwent early hemispherotomy acquired normal verbal intelligence, whereas the third, operated on at 38 months of age, remained with severe mental retardation. Conclusion: Isolated IS can be a presentation of hemispheric epilepsy related to a post-ischemic lesion. Efficiency of hemispherotomy to control seizures is very high and can prevent mental retardation. Predictive factors for a favourable post-operative development remain to be studied. any relevant benefit with regard to seizure outcome. As expected, postoperative hemianopia was found in all patients. In single cases, an ischemia of the basal ganglia, an infarction of the lateral thalamus or a bleeding in the postcentral region with (transient) motor or sensory deficit was observed. According to MRI criteria, in 10 patients (55%) complete resection or disconnection of the presumed epileptogenic lesion was achieved by MLE. In 14 patients (78%), histopathology revealed focal cortical dysplasia. 3 patients subsequently underwent hemispherotomy, which led to seizure freedom. Conclusion: MLE based on a thorough presurgical epilepsy evaluation can be a successful treatment option with acceptable risks, particularly in children with widespread dysplastic lesions.
p376 OUTCOME OF EXTRA TEMPORAL EPILEPSY SURGERY AND HEMISPHERECTOMY D. D. Ruikar, S. Jayalakshmi, M. Surath, M. Panigrahi, and R. Varma Krishna Institute of Medical Sciences, Secunderabad, India
Purpose: To assess the outcome of surgery in patients with medically refractory extra-temporal epilepsy (ETLE) and hemisperectomy patients evaluated with a non invasive protocol and to determine the predictors of outcome following surgery. Method: Retrospective analysis of pre-surgical (ictal EEG, MRI, fMRI, SPECT, PET, neuro-psychology) surgical and post surgery data was performed in 48 patients who underwent surgery for ETLE and 14 patients following hemispherectomy and who had at least one year post surgery follow up. Outcome was assessed according to Engel's outcome classification. Stepwise multiple logistic regression analysis was employed in data analysis. Result: Mean follow up was 32 months; 36(60%) were males. Intraoperative electro-corticography was done in 42 and cortical stimulation in 23 and neuronavigation in 6. Frontal resections were the commonest (28), followed by parietal resections. The pathology showed cortical dysplasia in 21, gliosis in 8 and low grade tumoral lesions in 10. Transient post surgery complications occurred in 3. Functional hemispherotomy was performed in 6 and vertical parasagittal hemispherectomy in 8. Hemispherical atrophy due to childhhood insult was the etiology in 6, hemispherical dysplasia in 5 and Rassmussen's encephalitis in 3. At last follow up seizure free outcome was noted in 37(77%) with ETLE and 9(75%) after functional hemispherectomy. After stepwise multiple logistic regression analysis, the variables found to be significant (P=<05) and predicting favourable outcome were normal IQ and absence of acute post operative seizures. Conclusion: Favourable outcome after epilepsy surgery can be obtained in patients with ETLE and hemispherectomy after evaluation with noninvasive protocol if presurgical evaluation is carefully planned.
p375 LONG-TERM OUTCOME AFTER MULTILOBAR EPILEPSY SURGERY D. Altenmller*, T. Bast, S. Schubert-Bast, K. Strobl, G. Wiegand, T. M. Freiman**, and J. Zentner** *Epilepsy Center, University Hospital Freiburg, Freiburg, Germany; Kork Epilepsy Centre, Kork, Germany; University Children's Hospital, Heidelberg, Germany; Epilepsy Center Kork, Kork, Germany; University Medical Centre SchleswigHolstein, Kiel, Germany; and **University Hospital Freiburg, Freiburg, Germany
Purpose: In patients with pharmacoresistant (multi-)focal epilepsy, multilobar surgery might be required if the epileptogenic area cannot be localized within a single lobe. We analyzed the pre- and postoperative findings of patients in whom a multilobectomy (MLE) was performed. Method: The data of all patients who underwent MLE at the Epilepsy Center Freiburg between 2001 and 2010 were retrospectively reviewed. Result: 18 patients (median age at MLE 71 months; median follow-up 31 months) fulfilled inclusion criteria. 10 patients received resection of two lobes (1 temporo-parietal; 3 parieto-occipital; 6 temporo-occipital). In 8 patients, resection of 3 lobes (all temporo-parieto-occipital) was performed, often after failure of more circumscribed previous surgical procedures. 11 patients (61%) gained seizure freedom, which mostly was accompanied by developmental progress and EEG recordings without epileptiform potentials after surgery. 3 patients (17%) did not experience
p377 SEIZURE OUTCOME AFTER HEMISPHERECTOMY DATA FROM THE SWEDISH NATIONAL EPILEPSY SURGERY REGISTER I. Olsson*, A. Edelvik, R. Flink, B. Rydenhag, and K. Malmgren *Institute of Clinical Sciences, Gothenburg, Sweden; Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Uppsala Akademiska Hospital, Uppsala, Sweden; and Sahlgrenska Academy at Gothenburg University, Gteborg, Sweden
Purpose: To present data from a population-based series of hemispherectomies.
111 Abstracts
Method: The Swedish National Epilepsy Surgery Register, which includes data on all epilepsy surgery procedures in Sweden since 1990 (completely prospective since 1995), was analysed for hemispherectomies 1995-June 2010. The outcome two years after surgery is presented. Twenty-three patients were identified, 12 males and 11 females. The median age at epilepsy onset was four months (range zero to 11 years). Preoperatively 19/23 (83%) had more than 50 seizures per month, 52% more than 100/month. The mean number of antiepileptic drugs (AEDs) was 2.3 (range 15). The side of operation was right in ten cases and left in 13. The median age at hemispherectomy was five years and three months (range six months to 20 years seven months). Result: The aetiology was developmental in 16 cases (12 with malformations of cortical development, four with hemimegalencephaly), acquired in four and progressive in one (Rasmussen). There were no major complications. Thirteen were seizure-free at the two-year followup (57%), three had more than 75% reduction in seizure frequency. Ten out of sixteen (63%) with developmental aetiology became seizure-free. Six out of the 13 seizure-free patients were off medication, the mean number of AEDs was 1.1 (range 03). Conclusion: The seizure outcomes in this population-based series of hemispherectomies were well in accordance with results of larger series. However, we had more patients with developmental aetiology than is usually reported, with equally good results, and most of the patients could stop or reduce medication, within two years after surgery. and in 77% of pure lesionectomies (P = 1.0, CI=95%). Thus there was not a significant improvement in outcome when MEG was incorporated but we found MEG to impact surgical approach and decision making in 60% of tumor cases. Conclusion: MEG contributes to surgical decision making in lesional epilepsy. Extra-operative utilization includes conventional localization of diploles to localize ictal onset, localization of epileptogenesis beyond the lesion and by allowing study of tissue that is difficult to study with other functional imaging modalities. Intra-operative utilization includes fusion with frameless navigation systems allowing guidance of IC-EEG electrode placement with greater accuracy. Outcome is not directly impacted by MEG incorporation but surgical approach often is.
p378 THE CONTRIBUTIONS OF MEG IN SURGICAL DECISION MAKING OF LESIONAL EPILEPSY J. P. Blount*, C. B. Smith, R. C. Knowlton, H. Kim, M. Goyal , C. J. Rozzelle*, P. Kankirawatana, and K. O. Riley *Children's of Alabama/University of Alabama at Birmingham, Birmingham, USA; and University of Alabama at Birmingham, Birmingham, USA
Purpose: Lesional epilepsy has traditionally referred to cases of tumors or vascular cavernous malformation that are readily visualized on MRI scans. However as the quality of imaging has improved other substrates have become increasingly defined as MRI evident lesions that are epileptogenic. The approach to such lesions remains controversial and incompletely understood. Resection of the lesion is straightforward and efficient yet may fail to control seizures in up to 40% of cases. Whether the lesion or peri-lesional tissue is primarily epileptogenic remains uncertain. The necessary extent of pre-operative evaluation and operative resection of peri-lesional tissue varies between experienced centers and remains controversial. We reviewed a large contemporary surgical series of lesional epilepsy to address the contribution of magnetoencephalography (MEG/MSI) studies to localization of lesional epilepsy. Method: A 10 year (20012011) retrospective review of a 2 institution (University of Alabama at Birmingham/Childrens Hospital of Alabama) experience was undertaken after IRB approval. Among 320 patients operated for lesional epilepsy a seizure occurrence rate of greater than or equal to two seizures was confirmed in 122 (44 adults, 78 Pediatric) patients. These were identified who had epilepsy, an abnormal pre-operative vEEG and a pre-operative MRI that revealed a lesion in the region of EEG abnormality. Lesions were broadly interpreted and included tumors (n = 46), FCD (n = 38), encephalomalacia from infarcts (n = 13), cavernous malformations (n = 6) and lesions associated with the phakamotoses (n = 10). Histopathologic confirmation was attained in all cases. MEG was utilized in 50 cases (9 tumors, 19 FCD, 1 cavernoma, 22 other). Result: The seizure freedom rate for pure lesionectomy was 81% for tumors with complete resection and 61% if residual disease was observed. Lesionectomy in FCD resulted in 50% class I outcome. MEG contributed to surgical localization by demonstrating dipoles both within the lesion and extending beyond the lesion into the peri-lesional tissue. Engel class I outcomes were seen n 77% of MEG directed lesionectomies
p379 COMPARATIVE STUDY OF EFFICACY AND SAFETY BETWEEN RADIOSURGICAL CALLOSOTOMY AND OPEN CALLOSOTOMY FOR LENNOX-GASTAUT SYNDROME IN A THIRD-LEVEL NEUROLOGICAL CENTER J. D. D. Del Castillo Calcneo*, D. San Juan Orta*, M. A. Alonso Vanegas, S. Moreno Jimenez*, and M. Herbas Rocha *National Institute of Neurology and Neurosurgery, Mexico City, Mexico; and Instituto Nacional de Neurologa y Neurociruga Manuel Velasco Suarez, Mexico City, Mexico
Purpose: Determine & compare the effect of surgical corpus callosotomy (SC) and radiosurgical corpus callosotomy (RC) in seizure frequency reduction in Lennox-Gastaut Syndrome (LGS) and to stablish safety of SC and RC in LGS. Method: Retrospective analysis (20042012) of patients who underwent either RC or SC was performed. Clinical, neurophysiological, neuroimaging and follow up variants were obtained and analyzed using descriptive statistics (means and standard deviations) as well as Student's T test for independent samples. Result: 33 subjects were included 21 [14 males] in SC and 12 [5 males] in RC. The average age at time of surgery was 20.6 7.9 years in RC and 25 7.9 in SC. Average time to diagnosis was 2.4 2.5 y in RC and 2.1 2.9 y in SC. All subjects were diagnosed with cryptogenic Lennox-Gastaut Syndrome and multi-focal epileptic activity. To perform the surgery in the RC group a mean dose of 43.2Gy (4) were used. Follow-up was performed at 12 (4) months. There was a decline in monthly seizure frequency for RC (-60%) as well as for SC (-55%) with no significant difference between them (p = 0.64). Tonic and Atonic seizures were the most reduced in both groups. In RC 6 subjects presented with complications related with severe cerebral edema. There were no complications reported on SC. Conclusion: RC shows similar efficacy compared with surgical corpus callosotomy in reducing seizure frequency in subjects with LGS. Even though there is a major incidence of complications in the RC group.
p380 CORRELATION OF FDG-PET AND VOXEL-BASED MRI MORPHOMETRY WITH INVASIVE EEG FINDINGS AND SURGICAL RESULTS IN MRI-NEGATIVE EPILEPSY J. Scholly*, A. M. Staack*, I. J. Namer, U. Kraus*, S. Bilic*, K. Strobl*, T. Bast*, M. P. Valenti-Hirsch, P. Kehrli, E. Hirsch, A. Schulze-Bonhage, J. Zentner, and B. J. Steinhoff*
112 Abstracts
*Kork Epilepsy Centre, Kork, Germany; University Regional Hospital Centre of Strasbourg, Strasbourg, France; Strasbourg University Hospital, Strasbourg, France; and Epilepsy Centre, University of Freiburg, Freiburg, Germany
Purpose: Conventional MRI fails to identify the lesion in about a quarter of patients with surgically remediable epilepsy. In MRI negative surgical candidates we investigated the localizing value of FDG-PET, voxel-based morphometric MRI analysis (VBM) and scalp video-EEG and correlated the findings with the epileptogenic zone defined by invasive EEG and histological findings after surgery. Method: 20 MRI-negative patients were prospectively investigated. Scalp video-EEG recordings, the visual analysis of FDG-PET overlaid onto a 3D-set of the patient's anatomic MRI scans as well as VBM MRI analysis based on algorithms of the statistical parametric mapping software (SPM5) were performed. 14 patients underwent invasive EEG, 12 were operated. Result: The epileptogenic zone defined by invasive EEG was temporal in three, temporal plus in two and extratemporal in nine cases, confirming the electro-clinical hypothesis after scalp recording in all but one case. The outcome was favorable (Engel class I) in ten patients (83%). The histological examination revealed focal cortical dysplasia (FCD) in nine cases and other pathologies in the rest. A topographic concordance with the epileptogenic zone could be demonstrated by FDG-PET in eight of nine FCD cases (89%). The VBM MRI analysis detected abnormalities suggesting FCD in six cases. Only two of them corresponded to the electro-clinical epileptogenic focus and only one to a confirmed FCD. Conclusion: Our data suggest a good localizing value of FDG-PET especially in cases of MRI obscure FCD, whereas a VBM MRI analysis showed low diagnostic sensitivity and specifity (11% and 33% respectively) in our series. Conclusion: Previous studies of HFO from intracranial microelectrodes and/or single neuron recordings consistently showed the frequencies at ictal onset above 100 Hz. In our study, HFO were preceded by lower frequency activity, and the presence of the lower frequencies synchronization correlated with post-operative seizure freedom. HFO may not be the first ictal manifestation in some cases, and the lower range ictal frequencies should not be overlooked. Larger studies are underway.
Medical Therapy and Pharmacology 4 Tuesday, 02 October 2012

p382 STATUS DYSTONICUS IN A CASE OF WILSON'S DISEASE O. Cokar, A. Mutlu, F. F. Ozer, M. Gurbuz, H. Acar, and F. Genc Haseki Educational and Research Hospital, Istanbul, Turkey
Purpose: Dystonia is a movement disorder characterized by sustained muscle contractions producing torsional and repetitive movements or abnormal postures. Status dystonicus is a generalized, intense and potentially fatal exacerbation of muscle contractures which is necessitated urgent hospital admission. It mainly affects patients with primary or secondary dystonia and is often triggered by fever, infection, trauma, surgery, abrupt introduction, withdrawal or change in medical treatment. We report one case of Wilson's disease presented with dystonic status. Method: A 49 year-old male with a previous diagnosis of Wilson's Disease treated trientine and zinc sulfate presented with generalized tonic clonic seizure. At time of admission he had hyperthermia up to 39 ordm; C. After control of seizure with diazepam and levetiracetam infusions the patient presented severe episodes of dystonia involved face and left arm and leg. Elevated serum creatine phosphokinase level was documented. Symptoms were resistant to conventional medication. Result: Gabapentin 900 mg/day, brought significant improvement and the patient remained clinically stable. Conclusion: Although status dystonicus is a rare but serious condition, prompt diagnosis is needed and gabapentin can be used to control severe episodes of dystonia.
p381 INTRACRANIAL EEG ICTAL ONSET FREQUENCY: HIGH OR LOW? J. Chung*, U. Maoz, N. Tsuchiya, O. Tudusciuc, S. Ye, A. Mamelak*, and D. Eliashiv* *Cedars-Sinai Medical Center, Los Angeles, USA; California Institute of Technology, Pasadena, USA; and Riken Institute, Tokyo, Japan
Purpose: Identifying ictal onset frequencies with wide spectrum EEG frequency analysis. Method: Eight patients with medically refractory partial epilepsy undergoing intracranial macroelectrode monitoring (4 depth electrodes, 4 subdural grids) were analyzed. Digital EEG data was sampled at 2 kHz at various intervals. Multiband frequency and power analysis were performed to characterize the predominating frequency during the interictal, pre-ictal, ictal, and postictal periods. Result: Thirty-one seizures14 seizures collected from subdural grid and 17 from depth electrodeswere analyzed. In each of the 18 seizures from six patients, the ictal onset was localized to one contact and was characterized by a significant increase of 10 30 Hz frequencies preceding the increase of 30 100 Hz frequencies by 3 seconds before propagation. Focal surgical resections were performed in the areas correlated to the synchronization of these alpha-beta range frequencies and HFO prior to and during the patients clinical seizures. These six patients have seizure-free outcomes confirming the localization of seizure onset. On the contrary, 13 seizures from two patients did not demonstrate the synchronization of alpha-beta range frequencies, and the patients did not achieve seizure freedom post-operatively.
p383 EARLY TREATMENT WITH LACOSAMIDE: RESULTS OF RELACOVA STUDY M. Garcs*, E. Lpez Gomariz, P. Giner, N. Torres, E. Noe, J. Lpez-Trigo**, C. Santafe, R. Muoz, M. Bonet, and V. Villanueva* *Hospital Universitario y Politcnico La Fe, Valencia, Spain; Hospital Luis Alcanyis, Xativa, Xtiva, Spain; Hospital Universsitario Dr. Peset, Valencia, Spain; Hospital Dr. Peset, Valencia, Spain; Hospital Valencia al MAr, Valencia, Spain; **Consorcio Hospital General Universitario Valencia, Valencia, Spain; Hospital Clinico Universitario Valencia, Valencia, Spain; Hospital de La Ribera, Alzira, Spain; and Hospital Arnau de Vilanova, Valencia, Spain
Purpose: To analyze early use of lacosamide (LCM) in RELACOVA study, a large multicenter prospective collection of patients on LCM in clinical practice. Method: Consecutive patients with partial epilepsy where LCM was used as 1st, 2nd or 3rd antiepileptic drug (AED) (monotherapy or
113 Abstracts
combination) and at least a follow-up of 3 months were studied. The information was obtained at baseline, 3, 6 and 12 months. Efficacy and adverse events (AE) were analysed. Concomitant AEDs and number of prior AEDs were also evaluated. Result: Fifty-six patients were included. Forty-nine patients were followed for 6 months and 40 patients for one year. Six patients had tried none AEDs, 20 patients one AED and 30 patients 2 AEDs. None patients withdrew before 3 months, retention rate at 6 months was 91.8% and at 12 months was 82.5%. Seizure free patients were 37.5%, 32.7% and 37.5% at 3, 6 and 12 months. Responders were 64.3%, 71.4% and 70% at 3, 6 and 12 months. No significant differences were observed according to the number of prior AEDs although a trend to a better response appeared when LCM was used as 1st or 2nd drug. Better response was observed when LCM was used with a non-sodium channel blocker (SCB (-)) (responder rate at 3 months showed p 0.033). AE were reported by 26.8%, 34.7% and 35% of patients at 3, 6 and 12 months. No differences were observed according to concomitant drugs. Conclusion: Efficacy of LCM in partial epilepsy is high when used early and seems to be better when used with SCB (-). Method: Children under 18 years of age, starting VPA or CBZ 01/11/ 0731/10/10 were ascertained using the hospital pharmacy database. Paper and electronic patient records were reviewed and data captured using a standard proforma. Simple descriptive statistics, Chi-squared, logistic regression and Kaplan-Meyer survival plots in SPSS (v19) were used. Result: 84 children (Males 45) aged 017 years (median 8.0) were identified, 44/84 had CBZ, 40/84 VPA, and 13/84 both. In 61/84 (73%) this was their 1st antiepileptic drug (AED). 30/44 (68%) on CBZ had focal epilepsies and 28/40 (70%) on VPA had generalized epilepsies. The audit comprised 29 person years of CBZ exposure, and 34 for VPA. 37/44 (84%) of patients on CBZ had >50% seizure reduction, including 13/44 (30%) seizure free. 36/40 (90%) on VPA had >50% seizure reduction, including 12/40 (30%) seizure free. 48/84 (57%) experienced adverse events, none serious, 7/44 (16%) on CBZ had increased seizures, 3/44 (7%) had rash; 6/40 (15%) on VPA complained of excessive weight gain. Conclusion: The audit of outcome showed CBZ and VPA to be effective first line AEDs, however we caution the use of CBZ as a first line AED because of the risk of seizure aggravation.
p384 ON THE USE OF INTRA RECTAL VALIUM IN PATIENTS WITH DRAVET SYNDROME: FAMILIES OPINION N. Coqu*, N. Chemaly, and R. Nabbout *Alliance Syndrome de Dravet, Brest Cedex 2, France; and Hpital Necker Enfants Malades, Paris, France
Purpose: Intra rectal Diazepam (DZ) remains the first rescue medication for acute prolonged convulsive seizures in children. In this study, we aimed at assessing the experience of the families of patients presenting Dravet syndrome (DS) concerning DZ use. Method: We invited 53 families of patients with DS to complete an auto-administered on-line questionnaire. Questions addressed the different aspects of intra rectal DZ use: usual administrators, and time, easiness, and risk of errors in the preparation and administration. Parents were questioned about their feeling concerning efficacy, usefulness in emergency setting, facility of its administration, and possible refuse of care givers to use it. Result: 52 families answered the questionnaire. DZ was usually administered by mothers and less frequently by other care givers. Almost all parents (92%) agreed on its efficacy. However, 50% found that preparation and administration are affected by errors especially when carried out of the parents presence. Many educational and non-medical institutions refused to use DZ. Conclusion: Parents confirm the efficacy of intra rectal DZ and emphasized the need for a medication that is easier to prepare and administer.
p386 BUCCAL PYRIDOXINE: RESCUE MEDICATION FOR PROLONGED SEIZURES IN CHILDREN WITH PYRIDOXINE DEPENDENT EPILEPSY, IN THE COMMUNITY SETTING L. Christodoulou*, and S. Beri *St Mary's Hospital NHS Trust, London, UK; and St Mary's Hospital, London, London, UK
Purpose: Pyridoxine dependent epilepsy (PDE) is a rare autosomal recessive disorder, characterized by early-onset, drug-resistant seizures, responsive only to pharmacological doses of pyridoxine. Mutations in the ALDH7A1 gene, which encodes the protein antiquitin, have been described. Buccal midazolam is now the standard treatment for prolonged seizures in children with epilepsy, in the community setting. We report two siblings from a consanguineous family of Asian origin with PDE, responding only to buccal pyridoxine for prolonged seizures. Method: A 4-year-old boy, developed multifocal seizures in the neonatal age, not responsive to standard anticonvulsants but responding to pyridoxine. Serum Pipecholic acid was high. Homozygous mutation in ALDH7A1 gene confirmed the diagnosis of PDE. Currently seizures are relatively well controlled on oral Pyridoxine. He does get intermittent, prolonged, generalized tonic-clonic seizures with infectious illness. Repeated doses of buccal midazolam and rectal diazepam have failed to control seizures in the community setting. Buccal pyridoxine has been extremely effective in stopping these seizures and preventing admissions to hospital. His 12-year-old sister was diagnosed with PDE, after his diagnosis became apparent. She has spastic quadriplegia with drug resistant multifocal epilepsy, currently well controlled on oral pyridoxine and Oxcarbazepine. Breakthrough prolonged seizures have failed to respond to benzodiazepines and only respond to buccal pyridoxine. Result: Not applicable. Conclusion: Buccal pyridoxine may have a role as rescue medication in controlling breakthrough seizures in children with PDE and should be considered as a therapeutic option in the community setting.
p385 A RETROSPECTIVE OBSERVATIONAL STUDY OF THE USE, EFFECTIVENESS, TOLERABILITY, AND RETENTION OF CARBAMAZEPINE AND VALPROATE IN CHILDREN AND YOUNG PEOPLE N. P. Docheva, and W. P. Whitehouse University of Nottingham, Nottingham, UK
Purpose: In 2006, ILAE criticised the lack of primary evidence for the use of Carbamazepine (CBZ) and Sodium Valproate (VPA) in the treatment of epilepsies in children and young people. This is a single centre, retrospective, registered clinical audit of process and outcome to assess the use, efficacy, tolerability, and retention of CBZ and VPA.
p387 COGNITIVE EFFECTS OF LACOSAMIDE D. Ijff, M. Majoie, and A. Aldenkamp Kempenhaeghe, Heeze, Netherlands
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Purpose: Lacosamide is a novel antiepileptic drug (AED) with potential benefit as adjunctive treatment in patients with partial-onset seizures.13 The cognitive effects have, as yet, not been studied. In this open clinical prospective study the cognitive effects of Lacosamide (VIMPAT) when used as adjunctive antiepileptic therapy in adolescent and adult patients with epilepsy was evaluated. Method: We included 33 patients (24 females, 9 males) aged between 1674 years (mean 37 years sd:14.5). All patients suffered from focal epilepsy: 42% had cryptogenic and 58% had symptomatic epilepsy. Patients were using LCS treatment with a daily dose of between 100 to 600 mg (mean daily dose of 298.2 mg/day). Mean follow-up time was 7 months (range 124). Patients were treated with up to four concomitant AEDs (mean: 1.9). Subjective complaints were evaluated using the SIDAED; effects on cognition were evaluated using the CVST, a test measuring speed of central information processing. Result: On the CVST a significant faster reaction time was found at the second evaluation (p=.010). On the SIDAED (subjective list of 46-items with possible AED-related complaints), patient complained more about their cognitive function at the second evaluation (p=.002). Conclusion: Lacosamide has a positive effect on the information processing speed although patients complained more, especially about their cognitive function. Possible explanations for this discrepancy are the effect of reduction of co-medication and increased worries of patients during a trial, causing overestimation of cognitive effects.
p389 LONG-TERM EFFICACY AND TOLERABILITY OF ZONISAMIDE AS ADJUNCTIVE THERAPY IN PATIENTS WITH REFRACTORY PARTIAL EPILEPSY A. La Neve*, N. Pietrafusa*, G. Pontrelli*, T. Francavilla*, V. Durante*, M. Ladogana*, T. Lisi*, and G. Boero *Policlinico di Bari, Bari, Italy; and SS. Annunziata Hospital, Taranto, Italy
Purpose: To assess long-term efficacy and tolerability of zonisamide (ZNS) as add-on treatment in patients with refractory partial epilepsy. Method: prospective, open label study conducted in 69 patients with refractory partial epilepsy. The study included 3 periods: Baseline (3 months); drug titration (> 2 months) to ZNS 300 mg/day; Observation, during which the ZNS could be increased up to the maximum tolerated dose. Inclusion criteria were: age >16 years, diagnosis of focal epilepsy, pharmacoresistance to at least 2 adequate previous antiepileptic drugs, stable concomitant antiepileptic therapy for 3 months during baseline. Exclusion criteria were: systemic or progressive neurological diseases, poor compliance, history of pseudo-seizures, pregnancy. Efficacy was evaluated comparing mean monthly seizures frequency during last three months of observation to baseline seizures frequency; statistical analysis was made using Poisson models for count data. Result: mean number of antiepileptic drugs before ZNS was 5.5 2.5; mean duration of follow-up was 19.5 months. 59 patients were included in the efficacy analysis and statistically significant reduction of the mean monthly seizures frequency was found at 12 months (19.14 38.60 vs. 9.73 18.10, p = 0.004) and at 24 months (19.14 38.60 vs. 8.86 17.51, p = 0.008). 24 patients (34%) complained adverse events wich led to drug discontinuation. Conclusion: Our data suggest good efficacy and a good tolerability of ZNS in the long term, especially considering the severe pharmacoresistance of our patients and the drug administration in polytherapy regimen.
p388 STEADY-STATE PHARMACOKINETICS AND TOLERABILITY OF ESLICARBAZEPINE ACETATE AND OXCARBAZEPINE IN HEALTHY VOLUNTEERS A. Falco*, M. Vaz-Da-Silva, T. Nunes, L. Almeida, and P. Soares-Da-Silva *4Health Consulting, Cantanhede, Portugal; University of Porto, Porto, Portugal; BIAL Portela & Ca. SA, So Mamede do Coronado, Portugal; and University of Aveiro, Aveiro, Portugal
Purpose: To investigate the steady-state pharmacokinetics and assess the tolerability of once-daily (QD) regimen of eslicarbazepine acetate (ESL) and twice-daily (BID) regimen of oxcarbazepine (Trileptal; OXC) in healthy volunteers. Method: Single centre, open-label, randomised, three-way crossover study in 12 healthy volunteers. The study consisted of two 8-day treatment periods separated by a washout period of 1015 days. In each treatment period the volunteers received either a daily oral dose of ESL 900 mg QD or ESL 450 mg BID (data not shown) or OXC 450 mg BID. Result: Eslicarbazepine was the major drug entity in plasma, accounting for 93.0% and 82.2% of total exposure with ESL 900 mg QD and OXC 450 mg BID, respectively. Eslicarbazepine Cmax (lmol/L) was 82% higher following ESL QD (87.34) compared to OXC BID (47.96). The ratio eslicarbazepine exposure(mmol*h/L)/dose(mmol) was 0.3733 (1133.71/3037.25) and 0.2695 (961.35/3567.60) for ESL and OXC, respectively, which translates in a 39% increase in efficiency of ESL versus OXC to deliver eslicarbazepine. ESL was 19% more efficient than OXC to deliver all active moieties. The extent of exposure to drug entities R-licarbazepine and oxcarbazepine was approximately 4-fold higher with OXC as compared with ESL. 30 and 18 treatment-emergent adverse events were reported in the OXC 450 mg BID group and the ESL 900 mg QD group, respectively. Conclusion: In comparison to OXC, administration of ESL resulted in 39% more eslicarbazepine, less R-licarbazepine and less oxcarbazepine, which may correlate with the tolerability profile reported with ESL.
p390 THE EFFECTS OF ESLICARBAZEPINE ON RECEPTORS, ION CHANNELS, ENZYMES AND TRANSPORTERS A. I. Loureiro*, M. J. Bonifcio*, L. Wright*, and P. Soares-DaSilva *BIAL Portela & Ca. SA, So Mamede do Coronado, Portugal; and University of Porto, Porto, Portugal
Purpose: This study was aimed to determine the interaction of eslicarbazepine, the main active metabolite of eslicarbazepine acetate, with potential biological targets. Method: Displacement of binding of specific ligands or substrates for 95 human G-protein coupled and ligand gated receptors, ion channels, enzymes and transporters was tested in the presence of 400 lM eslicarbazepine. Some eletrophysiological experiments were conducted with mouse N1E-115 cells and transfected cells expressing human Cav3.2 channels. Result: In the presence of 400 lM eslicarbazepine, no relevant interactions were observed with receptors (acetylcholine, adenosine, adrenergic, angiotensin II, cannabinoid, cholecystokinin, dopamine, GABA, glutamate, histamine, melatonin, neurokinin, neurpeptide Y, neurotensin, opioid, purine, serotonin, somatostatin and TRH), ion channels (type N calcium, GABA chloride, potassium ATP-sensitive and Ca2 + -activated), enzymes (acetylcholine esterase, acetylcholine transferase, carbonic
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anhydrase I and II, glutamic acid decarboxylase, COX-2, MAO-A and MAO-B, caspases [110], kinases [CK1d, Fyn, GSK3b, MAPK1, MAPK3, PKA, PKCb2, PHCz, ROCK2, SGK1] and nitric oxide synthase) and transporters (dopamine, noradrenaline, serotonin and GABA). Eslicarbazepine does not alter fast inactivation of voltage-gated sodium channel (VGSC), but reduced VGSC availability through enhancement of slow inactivation with an affinity to the slow inactivated state 5.9 times higher than to the channels in the resting state. Eslicarbazepine inhibited high and low affinity CaV3.2 inward currents with IC50`s of 0.4 and 62.6 lM, respectively. Conclusion: Eslicarbazepine is a selective slow inactivator of VGSC and potent Cav3.2 blocker devoid of effects upon major G protein coupled and ligand gated receptors, ion channels, enzymes and transporters. epilepsy after failure of at least 3 lifetime antiepileptic drugs. This study is being conducted to document patient demographics, lacosamide dosing, evolution of seizure control, and tolerability during a 6-month period in a real-life setting. Method: Patients were either already being treated (Group 1) or initiated treatment with lacosamide at enrollment (Group 2). Seizure control was determined by investigators using a 4-category scale (much improved, improved, stable, worsened), and tolerability by spontaneous patientreported treatment-related adverse events (AEs). Result: At interim analysis, 51 patients (28 female, age 1777 years) of 150 had completed an observational period of at least 4.5 months or had dropped out. Patients were highly refractory; all had 3 lifetime AEDs and 35% had 7. Following a mean study duration of 162 days, the mean daily lacosamide dose in Groups 1 and 2 was 347 and 297 mg (range 150600 mg), respectively. On study completion, seizure control was improved or much improved in 53% of patients in Group 1 and in 56% of Group 2. AEs occurred in 29% of patients (most frequently fatigue, dizziness or vertigo). Thirteen patients discontinued (29% of completers, 10% of enrolled) due to AEs (n = 8) or lack of efficacy (n = 5); 2 were lost to follow-up. Conclusion: Conclusion Data from this study so far suggest that in routine clinical practice, lacosamide is well tolerated and improves seizure control in highly refractory patients. Sponsored by UCB Pharma.
p391 A CASE REPORT OF THE SAFE USE OF LEVETIRACETAM IN A PATIENT WITH SICKLE CELL DISEASE A. Nitkunan, and T. Von Oertzen St George's Hospital, London, UK
Purpose: Levetiracetam is an anti-epileptic which is metabolised primarily in blood cells by enzymatic hydrolysis. The use of levetiracetam has not been reported in patients with sickle cell disease. Such patients with abnormal red blood cells may have difficulties metabolising levetiracetam. We report the use of levetiracetam in a patient with sickle cell disease. Method: A 22 year old Nigerian gentleman with sickle cell disease (homozygous SS) suffered from childhood bilateral strokes resulting in secondary generalised seizures that have been refractory to treatment. He has severe learning difficulties, spastic quadriplegia (uses a wheelchair), no speech and needs assistance with all activities of daily living. He has tried multiple anti-epileptic drugs and a ketogenic diet to no avail. He was started on levetiracetam during an episode of status epilepticus aged 20. He has now been on levetiracetam for just over 2 years and is currently on a dose of 1 g twice a day. Result: His seizures have remained refractory and he is on polytherapy. Although difficult to assess because of polytherapy, he has not suffered from any obvious side effects. Trough levetiracetam level was 19.1 (normal range (1037). In the 2 years prior to starting levetiracetam, he needed 21 units of blood to manage his anaemia. In the 2 years since starting levetiracetam, he has needed 7. Conclusion: This case illustrates that levetiracetam is not only safely tolerated in this patient with sickle cell anaemia but also that levetiracetam has not adversely affect his sickle cell disease.

p393 A RETROSPECTIVE OBSERVATIONAL STUDY OF COMPARATIVE LACOSAMIDE COST IN A REAL WORLD SETTING IN THE USA (VOYCE) S. Janssens*, H. Benhaddi*, T. Durgin, and S. Borghs *UCB Pharma, Brussels, Belgium; and UCB Pharma SA, Smyrna, GA, USA
Purpose: To compare the changes in treatment cost after lacosamide is added to monotherapy, versus after another antiepileptic drug (AED) is added, in patients with epilepsy in clinical practice. Method: This was a retrospective, observational, 1-to-n matchedcohorts study on a US claims database (SDI). The observation period was 6 months, both pre- and post-index. Index was defined as the date when lacosamide or one of eight other AEDs (controls) was added to existing therapy, which in this report consisted of AED monotherapy. Costs of inand outpatient visits, and medication for epilepsy and non-epilepsy, were collected from the database. The percentage in average change from preto post-index was calculated. Result: From pre- to post-index, total treatment cost decreased by 23.2% when lacosamide (n = 410) was added to monotherapy and by 5.5% with controls (n = 1908). Cost of inpatient visits decreased in both groups (96.5% with lacosamide versus 78.7% with controls), as did cost of epilepsy-related outpatient visits (26.4% versus 26.7%). Non-epilepsy-related outpatient visit cost remained stable with lacosamide (0.9%), but increased with controls (22.8%). AED medication cost increased by 153.8% with lacosamide and 66.1% with controls. Cost for non-AED medication increased in both groups; by 23.2% with lacosamide compared with 37.5% with controls. Conclusion: In clinical practice, adding lacosamide to monotherapy resulted in a greater decrease in total treatment cost compared with other AEDs, despite the greater increase in AED medication cost. Further analyses, looking at adding to polytherapy, and in focal epilepsy patients only, are ongoing. Sponsored by UCB Pharma.
p392 DRUG UTILIZATION STUDY WITH LACOSAMIDE IN DAILY CLINICAL PRACTICE IN BELGIUM: AN INTERIM ANALYSIS W. Van Paesschen*, H. Hauman, B. Legros, M. De Backer, E. Webster, and P. Dedeken *University Hospital Gasthuisberg, Lueven, Belgium; General Hospital St. Maarten, Duffel, Belgium; ULB Erasme Hospital, Brossels, Belgium; UCB Pharma, Brussels, Belgium; and UCB Pharma, Raleigh, USA
Purpose: Lacosamide was approved in 2010 for reimbursement in Belgium as add-on therapy for patients (16 years) with uncontrolled focal
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p394 HEPATOTOXICITY AND ANTICONVULSANT THERAPY IN CHILDREN AND ADOLESCENTS S. Karkelis, O. Papadaki-Papandreou, M. Lykogeorgou, M. Nikita, and G. Chrousos University of Athens, Athens, Greece
Purpose: Epilepsy and sufficient epilepsy treatment is a challenging problem for all clinicians taking care of children and adolescents. The aim of the study was to investigate the impact of epilepsy treatment on liver function tests in children and adolescents. Method: 287 children and adolescents(165 males, 122 females) epilepsy diagnosed during the last 5 years and aged 2 months-16 years were enrolled. All patients medical files were reviewed in order to estimate: age of treatment initiation, type of treatment, number of seizures per month, presence of status epilepticus and liver function tests using blood samples(ALT, AST, gGT, ALP, total bilirubin, direct bilirubin, total protein, albumin) at baseline, 6 months and 12 months after treatment initiation. Abnormal baseline liver tests were found in 29 patients who were excluded. SPSS-19 statistical software and x2-test were used for data statistical analysis. Result: Abnormal liver function tests were found in 48 patients, autoimmune hepatitis in 2 patients and acute liver failure in 1 patient. Statistical significant correlation(p < 0,05) was found between the number of seizures, the duration of therapy and the number of anticonvulsant drugs used from the one hand, and the liver enzymes values from the other hand: the higher the number of seizures and/or drugs used, the higher the liver enzymes values. The most hepatotoxic drugs were sodium valproate, carbamazepine and phenobarbital. Conclusion: Study results show very clearly that antiepileptic medications can cause liver dysfunction in children and adolescents, but in most cases this is a tolerable side effect and also that significant hepatotoxicity is very rare. mechanisms than other combinations. However, age, duration of exposure to AEDs, or frequency of seizures between 2 AEPs were not related the the score of AEP. Conclusion: The AE are related with burden of AEDs and the number of AEDs.
p396 COMPARISON OF DRIED BLOOD SPOTS AND PLASMA VALPROIC ACID AND CARBAMAZEPINE LEVELS S. T. Kong*, W. H. Lim, H. Y. Wang, Y. L. Ng, P. C. Ho*, and S. Lim *National University of Singapore, Singapore, Singapore; Singapore General Hospital, Singapore, Singapore; and Duke-National University of Singapore-Graduate Medical School, Singapore, Singapore
Purpose: Gas chromatography mass spectrometry (GC-MS) has been utilized for quantitative analyses of individual antiepileptic drugs (AEDs), one AED at a time but not simultaneously. To facilitate faster therapeutic AED monitoring process by healthcare professionals for patients with epilepsy (PWE), we (1) develop a GC-MS assay to concurrently measure both Valproic Acid (VPA) and Carbamazepine (CBZ) levels using one dried blood spot (DBS), and (2) correlate DBS measured VPA and CBZ levels with their plasma levels. Method: 30 PWE taking VPA and CBZ concomitantly were recruited. One DBS, containing ~15 lL of blood, was acquired for the simultaneous measurement of both drug levels using GC-MS. Measured DBS levels were correlated to therapeutic drug monitoring of plasma levels done at the hospital laboratory. Analysis was done using Statistical Package for Social Sciences (SPSS) version 19. Result: DBS levels were well-correlated to plasma levels: r2 > 0.85 for VPA and r2 > 0.73 for CBZ. Percentage differences between plasma and DBS levels were found to be consistent, with the mean values of 58.2% (95%CI=55.3561.14) for VPA and 3.1% (95%CI=-1.177.46) for CBZ. To calculate VPA plasma level, the conversion formula is 1.775 x (DBS VPA level) + 13.525. To calculate CBZ plasma level, the formula is 0.692 x (DBS CBZ level) + 2.644. Conclusion: The consistent correlation of DBS to plasma measured drug levels could make DBS an alternative tool for monitoring clinical levels of VPA and CBZ. Further study incorporating more patients and validation of the DBS assay are currently undergoing.
p395 ADVERSE EFFECTS OF AEDS ARE RELATED WITH DOSE AND NUMBER OF AEDS: OBSERVATIONAL STUDY WITH ADVERSE EVENT PROFILE S. E. Kim Haeundae Paik Hospital, Inje University, Busan, Korea
Purpose: Epilepsy surgery is available in selected patients, still the mainstream of treatment of epilepsy is antiepileptics (AED). The adverse effects (AE) of AEDs are major obstacle preventing maintenance of compliance and control of AE is important issue in clinical practice. Method: We performed this study with a brief 19-item self-report instrument, the Adverse Events Profile (AEP). Two AEPs were screened separately with interval of at least 1 month. The inclusion criteria were 1) taking AEDs for at least 6 months, 2) no change of AED dosage between 2 AEPs, 3) no adding on other medications between 2 AEPs, 4) at least 80% of compliance between 2 AEPs. AED loads were calculated as the sum of prescribed daily dose (PDD)/defined daily dose (DDD) ratios for each co-prescribed AED. Result: 218 patients were eligible for this study. 121 patients were on monotherapy and 97 patients were on polytherapy. The correlation between scores of 1st AEP (baseline) and 2nd AEP was excellent (Spearman correlation coefficient= 0.82, p < 0.0001). AED loads was related with the score of AEP?the score of AEP with over dose (>1 PDD/DDD) Vs with target dose (1 PDD/DDD), p = 0.006 by Mann-Whitney test?. Also, AEP scores were significantly different between patients with monotherapy and patients with polytherapy ?the score of AEP with monotherapy Vs polytherapy, p = 0.0002 by Mann-Whitney test?. In the 2 AEDs combination, the score of AEP was marginally lower in the combination of 2 AEDs acting on sodium channel blocker with multiple
p397 SERUM CONCENTRATIONS OF LACOSAMIDE IN PATIENTS WITH EPILEPSY: INFLUENCES OF DOSE, AGE, GENDER AND COMEDICATION S. Markoula*, R. Teotonio, P. Patsalos, and J. Duncan* *Epilepsy Society, Chalfont St Peter, UK; Hospitais da Universidade de Coimbra, Coimbra, Portugal; and UCL Institute of Neurology, London, UK
Purpose: To investigate the influence of lacosamide doses, gender, age and comedication on lacosamide serum concentrations in epilepsy patients. Method: Lacosamide concentrations were measured in the Therapeutic Drug Monitoring Unit at The Chalfont Centre for Epilepsy. Daily dose, demographic data and comedication were recorded. Patients were further stratified in two groups according to the interval between last lacosamide administration and blood collection (collection 2 h and 8 h after lacosamide administration or in 28 hours).
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Result: 299 patients (150 females) on lacosamide with a median age of 41 (1879) years and a median daily dose of 300 (50600) mg were retrospectively recruited. 123 patients took enzyme-inducing comedication. The mean lacosamide serum concentration was 28.5 16.4 lmol/l. 27,4% of the patients presented toxic symptoms at a mean lacosamide concentration of 29.6 15.4 lmol/L. This was independent of sodium channel acting comedication. Lacosamide concentrations were correlated with the dose and the intervals from dosing with no correlation with age. Women had higher concentrations (31.3 19.1 vs 25.6 12.6 lmol/L, p = 0.003) but not higher daily dose or percentage of toxic symptoms. Mean lacosamide concentrations were lower in patients taking enzyme-inducing comedication (21. 8 11.7 vs 33.8 18.6 lmol/L, p < 0,001). After multivariate regression analysis with respect to daily dose and intervals, enzyme-inducing medication and gender were statistically significantly related to serum concentrations. Conclusion: Lacosamide concentrations are decreased by enzymeinducing comedication. Higher concentrations in women could be explained by lower body mass and the absence of higher frequency of toxicity may imply a potentially higher female tolerance.
Brossels, Belgium; UCB Pharma, Brussels, Belgium; and UCB Pharma, Raleigh, USA
Purpose: Lacosamide was approved in 2010 for reimbursement in Belgium as add-on therapy for patients (16 years) with uncontrolled focal epilepsy after failure of at least 3 lifetime antiepileptic drugs. This study is being conducted to document patient demographics, lacosamide dosing, evolution of seizure control, and tolerability during a 6-month period in a real-life setting. Method: Patients were either already being treated (Group 1) or initiated treatment with lacosamide at enrollment (Group 2). Seizure control was determined by investigators using a 4-category scale (much improved, improved, stable, worsened), and tolerability by spontaneous patientreported treatment-related adverse events (AEs). Result: At interim analysis, 51 patients (28 female, age 1777 years) of 150 had completed an observational period of at least 4.5 months or had dropped out. Patients were highly refractory; all had 3 lifetime AEDs and 35% had 7. Following a mean study duration of 162 days, the mean daily lacosamide dose in Groups 1 and 2 was 347 and 297 mg (range 150600 mg), respectively. On study completion, seizure control was improved or much improved in 53% of patients in Group 1 and in 56% of Group 2. AEs occurred in 29% of patients (most frequently fatigue, dizziness or vertigo). Thirteen patients discontinued (29% of completers, 10% of enrolled) due to AEs (n = 8) or lack of efficacy (n = 5); 2 were lost to follow-up. Conclusion: Data from this study so far suggest that in routine clinical practice, lacosamide is well tolerated and improves seizure control in highly refractory patients. Sponsored by UCB Pharma.
p398 THE MTLE MOUSE AS A MODEL OF HUMAN TEMPORAL LOBE EPILEPSY: A COMPARATIVE STUDY OF THE MOST COMMONLY-USED ANTIEPILEPTIC DRUGS V. Duveau*, M. Langlois*, C. Bouyssieres*, T. Chabrol, C. Dumont*, A. Depaulis, and C. Roucard* *SynapCell, La Tronche, France; and Grenoble Institut des Neurosciences, Grenoble, France
Purpose: Mesiotemporal lobe epilepsy is one of the most prominent form of focal drug resistant epilepsy. A better understanding of mechanisms underlying this resistance would help to identify new active compounds. However, the need to have relevant models of MTLE has emerged. Recently, morphological and electroclinical features of MTLE has been observed in adult mice after unilateral injection of kainic acid in the dorsal hippocampus. In this work, we investigated the effect of the most commonly used antiepileptic drugs (AEDs) on the occurrence of focal and spontaneous hippocampal paroxysmal discharges (HPD). Method: Using the MTLE mouse model, we studied the dose response effect of commonly used AEDs, with acute or chronic administration protocols, on the occurrence and the duration of HPD by deep EEG recording. Result: Injection of classical AEDs (e.g. valproate and lamotrigine) failed to suppress HPD in a dose-dependent way. Indeed only high doses are effective (400 and 90 mg/kg, respectively) and are associated with modifications of the general behavior and/or EEG basal activity. A dosedependent suppression of HPD was observed with some other AEDs: carbamazepine, levetiracetam, vigabatrin, pregabalin, tiagabine and also with diazepam without noticeable behavioral or EEG side-effects. Conclusion: Our data show that our MTLE mouse model display a pharmacological profile similar to the one observed in patients suffering from refractory MTLE. The MTLE mouse model therefore provides a critical tool to find new treatments against epilepsy.
p400 EFFICACY OF PROGABIDE ADD-ON FOR REFRACTORY EPILEPSY X. Zou, T. Yuan, and B. Wu West China Hospital, Sichuan University, Chengdu, China
Purpose: Our objective is to evaluate the efficacy of progabide when used as an add-on treatment for people with refractory epilepsy. Method: We searched the Cochrane Epilepsy Group Specialized Register, the Cochrane Central Register of Controlled Trials, PubMed . We also contacted the manufacturers of progabide and researchers in this aspect. Result: A total of seven studies were included. For the whole studies, compared with placebo, progabide was more effective on refractory epilepsy (P < 0.01). The results of subgroup analysis showed that progabide was no effective on refractory partial epilepsy (P > 0.05), and more effective on refractory partial and generalized epilepsy (P < 0.01). Global clinical judgment OR, compared to placebo, was 14.42 (95% CI 3.6856.58). Conclusion: In people with refractory partial epilepsy, progabide when used as an add-on therapy may be not reduce seizure frequency. A large scale, randomized controlled trial with refractory partial epilepsy over a greater period of time is required in future clinical researches.
p399 DRUG UTILIZATION STUDY WITH LACOSAMIDE IN DAILY CLINICAL PRACTICE IN BELGIUM: AN INTERIM ANALYSIS W. Van Paesschen*, H. Hauman, B. Legros, M. De Backer, E. Webster, and P. Dedeken *University Hospital Gasthuisberg, Lueven, Belgium; General Hospital St. Maarten, Duffel, Belgium; ULB Erasme Hospital,
p401 LEVETIRACETAM IN ORAL SOLUTION SAFETY, TOLERABILITY AND EFFICACY IN PAEDIATRIC PATIENTS. SINGLE-CENTRE CLINICAL TRIAL O. Horak, and H. Oslejskova Epilepsy Center Brno, Brno University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic
118 Abstracts
Purpose: To determine the occurrence, severity and impact of adverse reactions (ADRs) of levetiracetam in oral solution, and so assess the grade of tolerability for this drug-form in paediatric patients. In addition, to focus on the spectrum of efficacy. Method: A single-centre clinical trial of 19 paediatric patients (median of age 2,67 years) treated with levetiracetam in oral solution over a 6 months period was conducted (monotherapy in 68,4%). Adverse drug reactions (ADRs) have been judged in 3-degree scale in three visits since the initiation of the treatment. Descriptive statistics such as minimum, maximum, mean, median and percentiles were used to describe the dose profile. 100% stacked bar graphs were used to describe proportions of patients according to number of seizures as well as according to ADRs severity. The assessment of efficacy was proved by means of non-parametric McNemar's test for the each type of epileptic seizure and each period individually. Result: 68, 4% of patients had no ADRs. In 31, 6% of cases the therapy was associated with (mostly weak) negative effect on mood, less often the nausea, aggressiveness, fatique or agility occurred. Only one patient had to stop the therapy. The relation with dose-titration profile wasn't improved. Statistically significant efficacy in secondary generalised tonic-clonic seizures and partial complex seizures was proved. Conclusion: Levetiracetam in oral solution seems to be well tolerated and safe drug in paediatric patients. ADRs, mostly of weak severity, were observed in 31, 6%. Emotional lability was the most frequent ADRs.
p403 EVALUATION OF SUDDEN UNEXPECTED DEATH IN EPILEPSY (SUDEP) OCCURRING IN LAMOTRIGINE (LTG) CLINICAL TRIALS T. Tomson*, L. Hirsch, D. Friedman, N. Bester, A. Hammer, M. Irizarry, L. Ishihara, A. Krishen, T. Spaulding, A. Wamil, and R. Leadbetter *Karolinska Institute, Stockholm, Sweden; Yale University, New Haven, CT, USA; New York University Langone Medical Center, New York, NY, USA; GlaxoSmithKline, Uxbridge, UK; and GlaxoSmithKline, Research Triangle Park, NC, USA
Purpose: Previous non-randomized studies reported an increased risk of SUDEP with LTG, but the association may be confounded by tonic-clonic seizure frequency, polypharmacy, and other potential SUDEP risk factors. We evaluated the risk of SUDEP with LTG compared to other AEDs and placebo in randomized controlled clinical trials conducted by GlaxoSmithKline. Method: Among 7,774 subjects in 42 randomized clinical trials, there were 39 all-cause deaths. Ten deaths occurred >2 weeks after discontinuation of study medication and were excluded from on-treatment events. Narrative summaries of deaths were independently reviewed by three clinical experts (TT, LH, DF), blinded to randomization arm. The risk of definite or probable SUDEP (Annegers criteria,1997) was compared between treatment arms for each trial design (placebo-controlled, activecomparator, cross-over), using exact statistical methods. Result: Of 29 on-treatment deaths, there were 8 definite/probable SUDEPs, 4 possible SUDEPs and 17 non-SUDEPs. The overall rate of definite/probable SUDEP for LTG was 2.2 per 1000-patient-years (95% CI=0.715.4). The odds ratios (OR) for on-treatment, definite/probable SUDEP in LTG arms relative to comparator arms, adjusted for length of exposure and trial, wereplacebo-controlled: OR=0.22 (95%CI 0.00 3.14; p = 0.26); active-comparator: OR=2.18 (95%CI 0.17117; p = 0.89); placebo-controlled cross-over: OR=1.08 (95%CI 0.0042.2; p = 1.0). Conclusion: Although the rate of SUDEP was not statistically different between LTG and comparator groups, the confidence intervals were wide and a clinically important increased or decreased risk cannot be excluded. Funded by GlaxoSmithKline.
p402 META-ANALYSIS OF NONPSYCHOTIC BEHAVIORAL TREATMENT EMERGENT ADVERSE EVENTS IN BRIVARACETAM AND LEVETIRACETAM DEVELOPMENT PROGRAMS J. DSouza*, M. Johnson, and S. Borghs* *UCB Pharma, Brussels, Belgium; and UCB Pharma, Raleigh, USA
Purpose: Brivaracetam (BRV) is a novel high-affinity synaptic vesicle protein 2A (SV2A) ligand which also displays inhibitory activity at neuronal voltage-dependent sodium channels. Levetiracetam (LEV) has been reported to be associated with behavioral problems. The objective of this analysis was to compare the incidence of behavioral problems in LEV and BRV clinical trials. Method: All global phase II/III double-blind placebo-controlled trials of adjunctive LEV (n = 4) and BRV (n = 5) in adults with uncontrolled focal epilepsy were analyzed. The number of subjects with at least one nonpsychotic behavioral treatment emergent adverse event (TEAE) was calculated for LEV, BRV, and respective placebo groups. Preferred terms were selected a priori from the psychiatric System Organ Class of MedDRA 9.0. Placebo-adjusted incidence was compared using the MantelHaenszel odds ratio stratified by study and 95% confidence interval. Result: The incidence of nonpsychotic behavioral TEAEs was found to be a third lower in BRV (83/1214, 6.8%) compared with LEV (73/672, 10.9%), whereas the incidences in placebo arms were similar (18/425, 4.2% and 17/351, 4.8%, respectively). The placebo-adjusted incidences were 2.6% for BRV and 6.1% for LEV. The odds ratio (BRV/LEV) was 0.68 [95% CI 0.321.45]. Subjects without concomitant LEV treated with BRV experienced a similar rate of nonpsychotic behavioral TEAEs (67/983, 6.8%) compared with subjects taking concomitant LEV (16/ 231, 6.9%) (corresponding placebo groups: 7/79, 8.9% versus 11/346, 3.2%). Conclusion: Despite lacking statistical significance, the absolute and placebo-adjusted incidence of nonpsychotic behavioral TEAEs were found to be numerically lower for BRV compared with LEV.

p404 IMPROVING THE DEVELOPMENT OF PROMISING DRUG CANDIDATES: PRECLINICAL SOLUTIONS IN A CHRONIC MOUSE MODEL OF MESIAL TEMPORAL LOBE EPILEPSY M. Langlois, C. Bouyssieres, V. Duveau, C. Dumont, and C. Roucard SynapCell, La Tronche, France
Purpose: Despite the development of new compounds, more than 30% of patients with epilepsy are still resistant to antiepileptic drugs (AEDs). Pharmaceutical industry clearly needs new preclinical strategies to improve AED discovery and development. Accordingly, chronic animal models of epilepsy that are resistant to one or several AEDs appear of great interest. Method: Mesiotemporal lobe epilepsy (MTLE) is the most common form of epilepsy that is refractory to AEDs. During the past ten years, a model of MTLE in adult mice has emerged where spontaneous recurrent focal seizures with mild behavioral expression are observed. A unilateral
119 Abstracts
injection of kainate (KA) into the dorsal hippocampus induces an ipsilateral hippocampal sclerosis along with the occurrence of spontaneous recurrent hippocampal paroxysmal discharges (HPD). These HPD develop during the first 3 weeks post KA and then remain stable and stereotyped for the whole life of the animals and occur spontaneously about 45 times per hour. Result: By using this MTLE mouse model, SynapCell has developed a broad range of preclinical solutions to better identify promising drug candidates. First, the in vivo screening protocol allows testing of small libraries of compounds and relies on quantitative EEG evaluation of the efficacy of new AEDs on highly recurrent HPDs. Then, promising drug candidates can be further studied for their dose response or long lasting effects with acute or chronic treatments. Conclusion: Altogether, this chronic model of MTLE reproduces behavioral, electroclinical and histopathological features of human MTLE and represents a unique tool to identify new AEDs potentially efficient in drug-resistant MTLE patients.
*University of Porto, Porto, Portugal; 4Health Consulting, Cantanhede, Portugal; BIAL Portela & Ca. SA, So Mamede do Coronado, Portugal; and University of Aveiro, Aveiro,
Purpose: In a phase II placebo-controlled, adjunctive therapy study in adult patients with partial-onset seizures eslicarbazepine acetate (ESL) 800 and 1200 mg/day once-daily (QD) was found to be efficacious and well tolerated. However, the same dose given twice-daily (BID) was not significantly more efficacious than placebo (Epilepsia, 48, 497504, 2007). The present study investigated the steady-state pharmacokinetics of QD and BID regimens of ESL in healthy volunteers. Tolerability was also assessed. Method: Single centre, open-label, randomised, three-way crossover study in 12 healthy volunteers. The study consisted of two 8-day treatment periods separated by a washout period of 1015 days. In each treatment period the volunteers received a daily dose of either ESL (900 mg QD or 450 mg BID) or 450 mg of OXC BID (data not shown). Result: Eslicarbazepine was the major drug entity in plasma, accounting for 94.6% and 94.0% of total exposure with ESL QD and ESL BID, respectively. Eslicarbazepine (Cmax) was 34% higher with ESL QD in comparison with ESL BID; AUC024 was 1133.71 and 1101.16 mmol*h/ L, respectively. Trough plasma eslicarbazepine before the last dose was 24.2% lower in the ESL QD in relation to ESL BID (27.45 and 36.21 lmol/L, respectively). A total of 18 treatment-emergent adverse events were reported in each group. Conclusion: In comparison to ESL BID, administration of ESL QD resulted in 34% higher maximum concentration of eslicarbazepine with similar overall exposure, which may correlate with the efficacy profile reported with ESL.
p405 ESLICARBAZEPINE DOES NOT ALTER PROLIFERATION AND CELL CYCLE DISTRIBUTION OF NEURAL STEM CELLS ISOLATED FROM THE RAT SUBVENTRICULAR ZONE M. I. Morte*, B. P. Carreira*, P. Soares-Da-Silva, I. M. Arajo, and C. M. Carvalho* *University of Coimbra, Coimbra, Portugal; University of Porto, Porto, Portugal; and University of Algarve, Faro, Portugal
Purpose: The effect on the proliferation of cultured neural stem cells isolated from the rat subventricular zone by eslicarbazepine acetate (ESL) and its metabolites, eslicarbazepine, and R-licarbazepine (R-Lic), carbamazepine (CBZ), oxcarbazepine (OXC), lamotrigine (LTG) and valproic acid (VPA) was investigated. Method: Cell proliferation was determined by the incorporation of 5ethynyl-2-deoxyuridine (EdU) after exposure of the cells to AEDs for 24 h, analysed by flow cytometry, together with cell cycle analysis performed by quantitative fluorescence. Result: The number of EdU-positive cells, with a median of 11.52 cells (10.4712.62 cells) in basal conditions, was decreased by all the AEDs except eslicarbazepine (10300 lM). Number of cells was decreased by 60% after treatment with ESL (30 lM), by 40% after treatment with RLic (1 lM), between 6575% after treatment with CBZ (10300 lM), by 60% or 90% after treatment with OXC (30300 lM), by 30% after treatment with LTG (300 lM), and by 98% after treatment with VPA (13 mM). Cells in G0/G1 phase increased by 2% after treatment with LTG (10 lM) and by 13% after treatment with VPA (1 mM). The number of cells in S phase was unchanged by the AEDs [median of 3.4% (2.6 4.0%)]. However, the number of cells in G2/M phase was increased by 90% after exposure to OXC (300 lM), while VPA (13 mM) decreased the number of G2/M cells by 6570%. Conclusion: Eslicarbazepine does not alter the proliferation of neural stem cells, whereas CBZ, OXC and VPA impaired proliferation of neural stem cells.
p407 RETIGABINE IN CHILDREN AND ADOLESCENTS WITH PHARMACORESISTANT EPILEPSIES DOCUMENTATION WITH THE ELECTRONIC TREATMENT DIARY EPI-VISTA K. Groening*, C. Dreiwes, U. Stephani, and R. Boor *Klinik fr Neuropdiatrie, Kiel, Germany; and Norddeutsches Epilepsiezentraum, Schwentinental, Germany
Purpose: The anticonvulsant retigabine exhibits a novel mechanism of action opening neuronal KCNQ/Kv7 potassium channels. Investigations on effects and side-effects in children/adolescents are not available. We analysed results of individual treatment trials with retigabine in pharmacoresistant epilepsies, focussing on seizure frequency and tolerability. Method: 17 patients (1;1019 years) with pharmacoresistant epilepsies were treated with retigabine. 12 patients documented seizures, dose and side effects in EPI-Vista. We compared the number of seizures during the last 4 weeks before starting treatment (baseline) with 4 weeks after reaching 10 mg/kg body weight/day or after the patient became seizure free or had side-effects earlier during titration. Result: The patients were treated with 413 (median 6.5) anticonvulsants before starting retigabine, duration of epilepsy was 1;211;6 (median 8) years. The number of seizures at baseline were 8 -1045 (median 47), in the observation period 0 1216 (median 15). Three patients showed reduction of seizure frequency of more than 50%. The dose when side effects were present was 6.3 16.37 (median 10,2) mg/kg body weight. 2 patients did not have side effects. The side effects were fatigue (6), speech disorders (3), concentration disturbances (3), sleep disorder, hallucination, agitation, increase of seizures, personality changes, elevated lever values. All side effects vanished when reducing/ending treatment with retigabine. Conclusion: Retigabine is a novel anticonvulsant which showed reduction of seizures in 3/12 children with pharmacoresistant epilepsies. Side
p406 STEADY-STATE PHARMACOKINETICS AND TOLERABILITY OF ONCE-DAILY AND TWICE-DAILY REGIMENS OF ESLICARBAZEPINE ACETATE IN HEALTHY VOLUNTEERS M. Vaz-Da-Silva*, A. Falco, T. Nunes, L. Almeida, and P. Soares-Da-Silva*
120 Abstracts
effects appeared in most cases but were reversible when withdrawing retigabine. Further studies are needed to define the group of children where retigabine is most powerful. (for early adverse effects in 8, non-compliance 3, and concomitant pseudoseizures 1). Among the 76 patients with informative trials, 15 (19.73%) became seizure-free for more than 12 months (mean: 17.67 months [SD: 3.67], range: 1224). The mean dose of lacosamide used in seizure-free patients was 246.66 mg. The mean number of previously failed AED trials, in the group of 76 patients, was 8 (SD: 3.51, range: 2 16). When the analysis was restricted to the 56 patients who had failed >6 AED trials, the number of seizure-free patients was 7 (12.5%). Conclusion: In our study, lacosamide showed a promising result when used as adjunctive therapy in patients with previously drug-resistant focal epilepsy, included those who had previously failed six or more AED trials.
p408 THE EFFECTS OF ESLICARBAZEPINE, R-LICARBAZEPINE, OXCARBAZEPINE, AND CARBAMAZEPINE ON SODIUM CURRENTS THROUGH NAV1.2 CHANNELS N. Pires*, K. Brady, S. Hebeisen, and P. Soares-Da-Silva *BIAL Portela & Ca. SA, So Mamede do Coronado, Portugal; BSYS GmbH, Witterswil; and University of Porto, Porto, Portugal
Purpose: Eslicarbazepine acetate (ESL) is a once-daily antiepileptic drug approved in Europe as adjunctive therapy for refractory partialonset seizures in adults. ESL undergoes rapid and extensive first pass metabolism via hydrolysis to eslicarbazepine, its major active metabolite. This study was aimed to determine the effects of eslicarbazepine, R-licarbazepine (minor metabolite of ESL), oxcarbazepine (OXC), and carbamazepine (CBZ) on the rat NaV1.2 sodium channel expressed in CHO cells. Method: About 2448 hours following transfection with rat NaV1.2 cDNA, cells were ready for electrophysiological experiments. The whole-cell patch-clamp technique was used to investigate the effects of eslicarbazepine, R-licarbazepine, OXC, and CBZ on NaV1.2 inward peak currents. These compounds were tested at various holding potentials ()80 mV and )70 mV). Result: With the exception of CBZ, the potency of inhibition was highly sensitive to the holding potential, increasing with depolarisation, but the affinity of eslicarbazepine was approximately 2- to 3-fold lower than that of OXC and CBZ in more depolarized conditions. CBZ was endowed with the potency to inhibit inward NaV1.2 sodium currents at )80 mV and )70 mV holding potentials. Conclusion: Eslicarbazepine demonstrated a greater selectivity for the inactive state of NaV1.2 sodium channels, which is the common feature of the rapidly firing neurons, over their resting state as compared to CBZ and OXC.
p410 PRESCRIBING PATTERN OF OLDER VERSUS NEWER ANTIEPILEPTIC DRUGS IN PATIENTS WITH EPILEPSY ATTENDING OUTPATIENT DEPARTMENT AT A TERTIARY CARE CENTRE IN INDIA R. Joshi, M. Tripathi, K. H. Reeta, and Y. K. Gupta All India Institute of Medical Sciences, New Delhi, India
Purpose: The purpose of the study was to evaluate the prescription pattern of older and newer antiepileptic drugs (AEDs) in a representative population of patients with epilepsy in the tertiary care centre in India. Method: Prescription data of epilepsy patients attending outpatient department (OPD) of neurology, AIIMS, India was obtained. Demographic variables including age, sex, diagnosis, age at onset of seizures, frequency of seizures and use of all AEDs were noted. Descriptive analysis of the use of older and newer AEDs was done and their different combinations were studied. Result: The prescriptions of 1000 epileptic patients attending OPD from 1st October 2010 to 27th January 2012 were evaluated. The demography showed 63.8% males, 36.2% females; mean age 23.2 years (range: 4 months to 77 years). The cases of generalized and focal seizures were 50.9% and 49.1% respectively. A total of 14 AEDs were prescribed. The four most frequently prescribed AEDs were sodium valproate (46.6%), clobazam (40.4%), carbamazepine (31.2%), levetiracetam (30.1%). The 32.7% of the patients received monotherapy. The common AEDs used on monotherapy were sodium valproate (33.6%), carbamazepine (25.1%), phenytoin (23.5%). Of the 67.3% patients received polytherapy, the three most common AED combinations were phenytoin + clobazam (46), sodium valproate + clobazam (40), phenytoin/carbamazepine + sodium valproate + clobazam (27). The recent AED introduced in 2010 in India was lacosamide used in 25 patients as add on therapy. Conclusion: An increasing trend of use of newer AEDs needs careful scrutiny in terms of cost, efficacy and safety.
p409 EFFICACY OF LACOSAMIDE IN DRUG-RESISTANT FOCAL EPILEPSY P. Bellas-Lamas, A. Fraga-Bau, B. Rodriguez-Acevedo, E. Alvarez-Rodriguez, and J. Gomez-Alonso University Hospital Xeral-Cies, Vigo, Spain
Purpose: New antiepileptic drugs (AEDs) may offer some hope in refractory epilepsy, even in cases of absolute drug-resistance, or grade III drug-resistance, that had failed >6 AED trials. We analyzed our experience with lacosamide in refractory focal epilepsy. Method: We prospectively registered all patients treated with lacosamide, as adjunctive therapy, until December 2010, at the Epilepsy Clinic of a general hospital in NW Spain. In February 2012, we evaluated the outcomes of those trials following the standards of the International League Against Epilepsy. The daily dose of lacosamide usually prescribed was 50 mg for two weeks, 100 mg for another two weeks, and then 200 mg or more. Result: Although lacosamide was administered to 88 patients with focal epilepsy, 12 trials were excluded because their results were undetermined
p411 RUFINAMIDE'S EFFICACY AND SAFETY IN CHILDHOOD EPILEPSY SECONDARY TO BRAIN MALFORMATIONS R. Moavero*, F. Madeddu, D. Pruna, M. Balestri, L. Fusco, N. Specchio, A. Capuano, D. J. Claps, P. Curatolo*, F. Vigevano, and R. Cusmai *Tor Vergata University Hospital of Rome, Rome, Italy; Azienda Ospedaliero Universitaria of Cagliari, Cagliari, Italy; and Bambino Ges Children's Hospital of Rome, Rome, Italy
Purpose: Aim of this study was the evaluation of efficacy and tolerability of add-on Rufinamide in pediatric patients with focal symptomatic epilepsy due to brain malformations.
121 Abstracts
Method: We retrospectively reviewed the clinical and electroencephalographic data of 32 children with refractory seizures symptomatic of different brain malformations treated with Rufinamide. Rufinamide was slowly titrated up to 40 mg/Kg/day (range 1040 mg/Kg/day, mean 33 mg/Kg/day). All the patients have been followed-up for at least 12 months. Patients have been considered responders if seizure reduction was greater than 50%. Result: 46,9% of patients presented focal cortical dysplasia, 21,9% pachygyria, 12,5% lissencephaly, 6,2% polymicrogyria, 3,1% ulegyria, 3,1% tuberous sclerosis, 3,1% schizencephaly, and 3,1% Walker-Warburg syndrome. 81,2% of patients presented focal motor and complex partial seizures, 15,6% focal motor seizures and the last patient only complex partial seizures. At the final follow-up 50% of patients were responders; seizure reduction was greater than 90% in 9% of cases, between 75% and 90% in 19%, and ranging from 50 to 75% in 22%. All the non-responder patients (50%) discontinued Rufinamide. 31,2% of subjects presented mild and transient side effects; only in one case (3,1%) dosage reduction was necessary to control irritability. In another patient (3,1%) Rufinamide was discontinued because of persisting anorexia. Conclusion: Our results suggest that Rufinamide can be considered as a valuable adjunctive therapeutic option for children presenting refractory seizures symptomatic of brain malformations. Purpose: To demonstrate the bioequivalence (BE) between two active product ingredient (API) sources of eslicarbazepine acetate (ESL) [current API source marketed formulation (MF) versus new API source to-be-marketed (TBM)]. Method: Two-centre, open-label, randomized, gender-balanced, singledose, laboratory-blinded, two-period, two-sequence, crossover study in two groups of 20 healthy subjects. Subjects randomly received on period 1 and 2 either a single tablet of ESL (MF) or a single tablet of ESL (TBM), separated by a wash-out of at least seven days between doses. Two dosage strengths were studied 400 mg in one group and 800 mg in the other. For all subjects, blood samples (4 mL) were drawn for the assay of plasma ESL and its active metabolite eslicarbazepine at pre-dose and then 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose on each dosing period. Result: At the two studied dosage levels, 400 mg and 800 mg, the 90% back-transformed confidence intervals for Cmax, AUC0-t and AUC0- ratios of the Test formulation (TBM) and Reference (MF) formulation were all contained in the bioequivalence range of 0.8 1.25. Additionally, at both dose levels, no evidence of difference between Test and Reference products in tmax (p > 0.05) was found. Study treatments, whatever the dosage and formulation, were well tolerated. Conclusion: The oral formulations containing 400 mg or 800 mg of ESL of the TBM source are bioequivalent to the MF source for both 400 mg and 800 mg of ESL.
p412 ON THE USE OF INTRA RECTAL VALIUM IN PATIENTS WITH DRAVET SYNDROME: FAMILIES EXPERIENCE R. Nabbout*, N. Chemaly, and N. Coque *Hopital Necker-Enfants Malades, Paris, France; Paris, France; and Brest, France
Purpose: Intra rectal Diazepam (DZ) remains the first rescue medication for acute prolonged convulsive seizures in children. In this study, we aimed at assessing the experience of the families of patients presenting Dravet syndrome (DS) concerning DZ use. Method: We invited 53 families of patients with DS to complete an auto-administered on-line questionnaire. Questions addressed the different aspects of intra rectal DZ use: usual administrators, and time, easiness, and risk of errors in the preparation and administration. Parents were questioned about their feeling concerning efficacy, usefulness in emergency setting, facility of its administration, and possible refuse of care givers to use it. Result: 52 families answered the questionnaire. DZ was usually administered by mothers and less frequently by other care givers. Almost all parents (92%) agreed on its efficacy. However, 50% found that preparation and administration are affected by errors especially when carried out of the parents presence. Many educational and non-medical institutions refused to use DZ. Conclusion: Parents confirm the efficacy of intra rectal DZ and emphasized the need for a medication that is easier to prepare and administer.
p414 MODELLING THE COGNITIVE EFFECTS OF COMMON ANTIEPILEPTIC DRUGS: A CROSS SECTIONAL HEAD-TO-HEAD COMPARISON USING THE EPITRACK C. Helmstaedter, and J. Witt Bonn, Germany
Purpose: Although the cognitive side effects of AEDs are more or less known, the risk profiles of the respective drugs must be extrapolated from a plethora of studies with heterogeneous study designs, control conditions and assessments. In this regard, we aimed at a cross-sectional head-to-head comparison of the cognitive effects of common AEDs given in mono- or polytherapy and using the same screening test. Method: Using a cross-sectional controlled study design, 542 untreated epilepsy patients, 1074 patients on mono-, and 1357 patients on polytherapies were evaluated in regard to a set of executive functions. For this purpose, we applied a 12-minute tool (EpiTrack) which, in its second edition, had newly been standardized for an age range of 1687 years. in 689 healthy subjects. Result: In the off drug condition, 42% of the patients were impaired. Compared to this, the odds ratios increased from 1.4 with monotherapy to 7.8 with 4 drugs in polytherapy. Linear regression indicated worse EpiTrack performance with a higher number of AEDs, TPM, ZNS, or GBP and better performance with LEV or LTG. Education appeared to be a protective factor, female gender an additional risk factor. The regression model, however, only explains 23% of the observed variance. Following odds ratios, AEDs could be grouped into three classes with ratios of 1.9 2.6 (LTG, LEV, CBZ, OXC), 2.63.6 (VPA, PB, PGB, LCM, GBP, PHT) and 4.15.3 (ZNS, TPM, CLB). Conclusion: This is the first study, which, using a single assessment tool, models and replicates the known cognitive effects of common AEDs in a cross-sectional study design.
p413 COMPARATIVE BIOAVAILABILITY STUDY OF TWO DIFFERENT SOURCES OF ESLICARBAZEPINE ACETATE IN HEALTHY SUBJECTS R. P. Sousa*, R. Lima*, T. Nunes*, and P. Soares-Da-Silva *BIAL Portela & Ca. SA, So Mamede do Coronado, Portugal; and University of Porto, Porto, Portugal
122 Abstracts

p415 DESIGN OF A PHASE III, DOUBLE-DUMMY, ACTIVECONTROLLED, MULTI-NATIONAL NON-INFERIORITY MONOTHERAPY TRIAL OF ESLICARBAZEPINE ACETATE VERSUS CONTROLLED-RELEASE CARBAMAZEPINE IN ADULTS WITH PARTIAL-ONSET SEIZURES J. Moreira*, E. Trinka, F. Mota*, T. Nunes*, and P. Soares-DaSilva *BIAL Portela & Ca. SA, So Mamede do Coronado, Portugal; Paracelsus Medical University, Salzburg, Austria; and University of Porto, Porto, Portugal
Purpose: Eslicarbazepine acetate (ESL) was approved by the European Medicines Agency in 2009 as adjunctive therapy in adults with partialonset seizures, with or without secondary generalization. This phase-III, randomised, double-blind, active-controlled, non-inferiority study aims to demonstrate the efficacy and safety of once-daily ESL as monotherapy treatment for newly diagnosed adults with POS in comparison to twicedaily controlled-release carbamazepine (CBZ-CR). Method: Patients (>18 year) with >2 unprovoked seizures in the past year and >1 in the last 3-months will be randomised in a 1:1 ratio to receive ESL 800 mg once-daily or CBZ-CR 200 mg twice-daily during a 26-week evaluation-period. In case of seizure occurrence during the evaluation-period, subjects are titrated to dose-levels B (1200 mg once-daily/ 400 mg twice-daily) and C (1600 mg once-daily/600 mg twice-daily). To assess maintenance of effect over 1-year, a 26-week maintenance-period will follow. Exit criteria include seizures at dose-level C at evaluationperiod or at any dose-level in the maintenance-period. The primary endpoint is seizure-freedom in the 26-week evaluation-period at the last received dose level. The sample size was calculated to achieve a > 90% power to establish non-inferiority, using a )12% margin. Secondary endpoints include tolerability, QOLIE)31, sedation, and clinical laboratory assessments. Result: The study is expected to be completed by the end of 2013. Conclusion: The use of a non-inferiority design implies the pre-definition of a clinically relevant margin and adequate power to detect noninferiority versus a gold standard. To our knowledge this is the first pivotal study to fully achieve those requirements.
Method: Twelve patients affected by focal epilepsy underwent A-PSG, MSLT, and a subjective evaluation of nocturnal sleep by means of PSQI and daytime somnolence by means of the Epworth Sleepiness Scale (ESS), before and after 3 month treatment with ZNS. Recordings were evaluated in according to standard criteria. The study was single-blind. PSG data, MSLT, both PSQI and ESS scores were calculated before and after ZNS treatment. Statistical analysis was performed by means of the non-parametric Wilcoxon test. Bonferroni correction was applied when required. Result: ZNS induced a decrease of seizures >50% in 9 out of 12 patients (75%). ZNS did not induce any significant differences of nocturnal PSG parameters and mean sleep latency as measured by means of MSLT. No significant changes were detected in both PSQI e ESS scores after ZNS addition. Conclusion: To our knowledge this is first study focusing about the effects of ZNS on nocturnal sleep and diurnal sleepiness. Firstly ZNS adjuntive treatment seems to be effective in focal epilepsy in our narrow sample as reported in several clinical trials3. In addition ZNS does not induce negative effects on sleep-wake cycle and diurnal sleepiness as evaluated by means of a comprehensive objective e subjective evalution.
p417 EFFICACY OF PERAMPANEL, A SELECTIVE AMPA ANTAGONIST, IN COMPLEX PARTIAL AND SECONDARILY GENERALIZED SEIZURES: A POOLED ANALYSIS OF PHASE III STUDIES IN PATIENTS WITH TREATMENT-RESISTANT PARTIAL-ONSET SEIZURES B. J. Steinhoff*, H. Gauffin, P. Mckee, D. Squillacote, H. Yang, D. Kumar, and A. Laurenza *Epilepsiezentrum Kork, Kehl-Kork, Germany; Linkping University, Linkping, Sweden; The James Cook University Hospital, Middlesbrough, UK; and Eisai Neuroscience Product Creation Unit, Woodcliff Lake, NJ, USA
Purpose: In this sensitivity/subgroup analysis we summarize the efficacy of perampanel in both complex partial plus secondarily generalized seizures (CPS+SGS) and secondarily generalized seizures (SGS) across phase III studies according to actual doses of perampanel achieved. The randomized population, with prespecified endpoints, will be presented in the poster. Method: Following Baseline, patients were randomized to once-daily placebo, perampanel 2, 4, 8, or 12 mg. Endpoints included percent change in CPS+SGS and SGS frequency/28 days (vs Baseline), and CPS+SGS and SGS 50% responder rates. Analyses were based on last actual perampanel doses in patients completing 19 weeks treatment (excluding Central/South American patients due to significant treatmentby-region interactions). Result: Overall, 442, 180, 172, 431, and 254 patients were randomized to placebo, perampanel 2, 4, 8, 12 mg, respectively; 1264 patients completed the studies. The numbers of patients achieving each actual dose were: 348, 161, 159, 46, 287, 14, 114 for placebo, perampanel 2, 4, 6, 8, 10, 12 mg. Median percent changes in CPS+SGS frequency were )14.6% (n = 319), )26.6% (n = 150), )35.6% (n = 145), )35.9% (n = 267), )30.3% (n = 104) for placebo, perampanel 2, 4, 8, 12 mg actual doses. Responder rates were 21.9%, 29.3%, 37.9%, 40.1%, 39.4%. Median percent changes in SGS frequency were )19.5% (n = 133), )27.9% (n = 60), -54.6% (n = 66), )60.8% (n = 112), )56.0% (n = 43) for placebo, 2, 4, 8, 12 mg. Responder rates were 38.3%, 43.3%, 53.0%, 56.3%, 53.5%. Conclusion: In this sensitivity/subgroup analysis of phase III trials, perampanel decreased CPS+SGS and SGS frequency and increased responder rates, compared with placebo. Support: Eisai Inc.
p416 ZONISAMIDE AS ADD-ON TREATMENT DOES NOT AFFECT NOCTURNAL SLEEP AND VIGILANCE IN PATIENTS AFFECTED BY FOCAL EPILEPSY: A POLYSOMNOGRAPHIC STUDY A. Romigi, F. Izzi, F. Placidi, S. Zannino, E. Evangelista, C. Del Bianco, F. Cum, and M. G. Marciani University of Rome Tor Vergata, Rome, Italy
Purpose: Epilepsy are particularly sensitive to the sleep disruption induced by antiepileptic drugs (AEDs). AEDs have the potential to either improve or worsen sleep and sleep disorders in epileptic patients. Zonisamide (ZNS) is a new AED approved in USA and Europe as adjunctive therapy for focal epilepsy. To date the effects of ZNS on sleep and vigilance in focal epilepsy are not yet studied. The purpose of our study is to evaluate the effects of ZNS adjunctive therapy on nocturnal sleep by means of ambulatory polysomnography (A-PSG) and Pittsburgh Sleep Quality Index (PSQI) and on daytime somnolence by means of multiple sleep latency test (MSLT) and Epworth Sleepiness Scale (ESS) in focal epilepsy as standard methodology.
123 Abstracts
p418 LONG-TERM COGNITIVE EFFECTS OF TREATMENT WITH MONOTHERAPY CARBAMAZEPINE (CBZ) AND VALPROATE (VPA) D. Ijff, M. Majoie, and A. Aldenkamp Kempenhaeghe, Heeze, The Netherlands
Purpose: So far the information on cognitive effects of antiepileptic treatment is based on short-term trials. The long-term effects have, as yet, not been studied. Mostly fluid cognitive functions are assessed as no changes are expected in higher-order function in such a short period. It is unknown whether higher functions are at risk with longer treatment intervals. In this open clinical cohort study the long-term cognitive effects of monotherapy carbamazepine and valproate were evaluated in children and adults with epilepsy. Method: Patients were only included when they had been on monotherapy CBZ or VPA from epilepsy onset without any switch to other medication. Outcome measures included WISC-III/WAIS-III1,2 and cognitive tests (FePsy)3. Result: Thirty-five children (average treatment length 3.8 years) and 22 adults (average treatment length 7.8 years) were included with CBZ. Forty-six children and 17 adult patients were included with VPA. Average length of treatment in both VPA-groups was 3.5 years. Signs for mild mental/psychomotor slowing without any differences between CBZ and VPA were found. Children on CBZ had lower intelligence scores than on VPA. However, this result was not found for adults. The two treatment groups did not differ in type of epilepsy. There is a high inverse correlation between length of treatment and IQ-scores only for children on CBZ. Conclusion: Our study shows evidence that at long-term CBZ may impact higher-order cognitive function and even intelligence in children. As this effect was not found for adults, this suggests that longterm treatment with CBZ may influence the maturation of the brain in children. in the first twenty-four hours following incubation regardless of drug loading percentage, and then demonstrated a steady release until eight weeks. We confirmed the neuronal loss in CA1 in the lesioned hippocampus of tetanus-treated rats. Spontaneous seizures which resemble human generalized tonic clonic seizures, absence and myoclonic seizures have been observed. The PHT-loaded microsphere implanted rats exhibited a reduced number of convulsive seizures as illustrated by attenuated seizure scores. Conclusion: This study demonstrates the efficacy of PHT-loaded PCL microspheres in attenuating generalized seizures in a rat model of temporal lobe epilepsy. This may warrant further studies for focal delivery of polymer-based anticonvulsants in treating partial and secondary generalized seizures.
p420 SEIZURE FREEDOM ON ANTIEPILEPTIC MONOTHERAPY L. J. Stephen, K. Kelly, O. Mcgowan, V. Politi, and M. Brodie Western Infirmary, Glasgow, UK
Purpose: The goal of antiepileptic drug (AED) treatment is sustained seizure freedom on monotherapy with no or acceptable side effects. This project examined characteristics of patients seizure-free on 1 AED for 1 year. Method: Data were acquired by Epilepsy Unit database and case sheet interrogation of 6821 patients registered between 1982 and 2011. Result: Seizure freedom was achieved on 17 different monotherapies in 1425 (20.9%) patients (687 men, 738 women, aged 1894 years [median 46 years]). Of these, 1131 (79.3%) had partial + secondary generalised tonic-clonic seizures [GTCS], 294 (20.7%) had idiopathic generalised epilepsies. First monotherapy produced complete seizure freedom in 866 (60.7%) patients; the remainder controlling on 2nd (n=309, 21.7%), 3rd (n=217, 15.2%), 4th (n= 31, 2.2%), or 5th (n=2, 0.2%) schedules. The commonest AEDs used were sodium valproate (n=443, 31.1%), carbamazepine (n=382, 26.8%), lamotrigine (n=318, 22.3%) and levetiracetam (n=82, 5.8%). Of patients receiving sodium valproate, 67% (n=298) took 1000mg/day (median 1000, range 4003000), 66% of carbamazepinetreated patients received 600mg/day (median 600, range 2002000), 75% of lamotrigine-treated patients received 200mg/day (median 200, range 25700), and 74% of levetiracetam-treated patients received 1000mg/day (median 1000, range 5003000). There was no relationship between AED dosing and schedule. Side effects (108 [81%] neurotoxicity, 26 [19%] other) were reported by 134 (9.4%) patients, particularly those taking carbamazepine (60 of 382, 16%; others 73 of 1043, 7%; p<0.001). Conclusion: Although the majority of patients became seizure-free on their first monotherapy, a substantial minority controlled on later schedules. Doses were often modest. Side effects were twice as likely with carbamazepine.
p419 IMPLANTATION OF PHENYTOIN-LOADED POLYCAPROLACTONE MICROSPHERES IN A RAT MODEL OF TEMPORAL LOBE EPILEPSY J. Sui*, A. Halliday, K. Mclean*, T. Wilson, S. Moulton, G. Wallace, R. Balson, A. Lai*, N. Beattie*, and M. Cook* *St Vincent's Hospital, Melbourne, Vic, Australia; University of Melbourne, St. Vincent's Hospital, Melbourne, Vic, Australia; St Vincent's Pathology, Melbourne, Vic, Australia; University of Wollongong, Wollongong, NSW, Australia; and Bionics Institute, Melbourne, Vic, Australia
Purpose: The main purpose of this study is to explore the potential therapeutic effects of intracerebral polymer-based anticonvulsant delivery in treating generalized and partial seizures. Method: Phenytoin (PHT)-loaded polycaprolactone (PCL) microspheres were produced by performing an emulsion process. The actual drug loading and releasing profile was determined using high performance liquid chromatography. Temporal lobe epilepsy model was established by unilateral injections of tetanus toxin into right hippocampus of adult male Sprague-Dawley rats. PHT PCL spheres were ipsilaterally injected in the adjacent region. Seizure phenotypes and cortico-electrical discharges were detected and recorded by a twenty-four hours video electroencephalography system equipped with ProFusion. Animals were killed eight weeks after toxin injection, and biocompatibility was assessed by immunohistochemistry. Result: The PCL microspheres were 3050 lm in diameter. In vitro study revealed PCL microspheres released a substantial amount of PHT
p421 ESLICARBAZEPINE ACETATE AND PLASMA LEVELS OF COMBINED ANTIEPILEPTIC DRUGS: A POPULATION PHARMACOKINETICS EVALUATION BASED ON DOUBLE-BLIND PHASE III CLINICAL STUDIES M. Bialer*, A. Falco, R. Costa, N. Lopes, T. Nunes, and P. Soares-Da-Silva *The Hebrew University of Jerusalem, Jerusalem, Israel; 4Health Consulting, Cantanhede, Portugal; BIAL - Portela & Ca. SA, So Mamede do Coronado, Portugal; and University of Porto, Porto, Portugal
124 Abstracts
Purpose: Eslicarbazepine acetate (ESL) is a once-daily voltage-gated sodium channel blocker approved in Europe for use in adults as adjunctive therapy for refractory partial-onset seizures (POS) with or without secondary generalisation. The variability of the population pharmacokinetics (PK) and systemic plasma exposure to concomitant antiepileptic drugs (AEDs) in treating patients with refractory POS were analysed to determine the potential influence of ESL on the metabolism and PK of concomitant AEDs. Method: Plasma concentrations of eslicarbazepine (main active metabolite of ESL) and other concomitant AEDs were obtained from 641 patients receiving ESL. Data were analysed using nonlinear mixed-effect modelling (NONMEM) methods. Plasma exposure PK parameters were calculated from individual parameters estimates derived from the model. A population PK model of trough (Cmin,ss) eslicarbazepine plasma concentrations at steady-state was fitted. Result: No clinically relevant changes in the mean end/initial Cmin,ss ratios of concomitant AEDs were calculated for placebo, ESL 400 mg and 800 mg dose groups. In ESL 1200 mg treated patients, mean end/ initial Cmin,ss ratios of carbamazepine (CBZ), lamotrigine (LTG), and topiramate (TPM) were reduced by 13%, 25% and 16%, respectively. ESL slightly increased the oral clearance (CL/F) of CBZ, LTG, and TPM up to 14%, 12%, and 16%, respectively, but did not affect that of clobazam, gabapentin, phenytoin, phenobarbital, levetiracetam and valproate. Conclusion: This pop-PK analysis based on integrated data from three phase III clinical studies suggests that the pharmacokinetic effect of eslicarbazepine acetate on the clearance of concomitant AEDs is unlikely to be clinically relevant in most cases.
p423 OUTCOMES IN NEWLY DIAGNOSED EPILEPSY WHY DO PATIENTS REMAIN UNCONTROLLED? M. Brodie*, D. Goldberg*, K. Kelly*, L. J. Stephen*, and P. Kwan *Western Infirmary, Glasgow, UK; and Prince of Wales Hospital, New Territories, Hong Kong
Purpose: More than 30% of a cohort of 1098 patients with newly diagnosed epilepsy followed for 226 years were uncontrolled at the time of analysis (Brodie et al. Neurology, in press). Their clinical details were examined to see how many fulfilled the ILAE criteria for drug-resistant epilepsy (Kwan et al, Epilepsia 2010; 10691077). Method: Casesheets from 361 patients were reviewed and data entered into a web-based drug response classifier programme (Hao et al. Epilepsy Behav 2011; 388390). Those that were categorised as undefined were investigated further. Result: Thirty-two patients had died and data were incomplete for 9 patients. A further nine had taken part in head-to-head placebo-controlled trials. Of the remaining 311 patients, 136 (43.7%) fulfilled the definition of drug-resistant epilepsy. The remaining 175 (56.3%) were classified as undefined. A number of reasons were identified, including trying one drug, inadequate dosing, intermittent compliance, adverse effects at minimal dosage, psychiatric problems affecting documentation, erratic attendance, social issues such as imprisonment, alcohol and recreational drug use, and patient choice (median reasons 2, range 14). Conclusion: More than half of the patients with uncontrolled epilepsy did not fulfil the ILAE criteria for drug-resistant epilepsy. Further pharmacological treatment may improve their seizure control.
p422 EFFECTS OF ESLICARBAZEPINE AND LACOSAMIDE ON SLOW AND FAST INACTIVATION OF VOLTAGEGATED SODIUM CHANNELS M. J. Bonifcio*, S. Hebeisen, and P. Soares-Da-Silva *BIAL - Portela & Ca. SA, So Mamede do Coronado, Portugal; BSYS GmbH, Witterswil, Switzerland; and University of Porto, Porto, Portugal
Purpose: This study was aimed to determine the effects of eslicarbazepine, the major active metabolite of ESL, and lacosamide (LCS) on the fast and slow inactivated states of voltage-gated sodium channels (VGSC). Method: The whole-cell patch-clamp technique was used to investigate the effects of eslicarbazepine and LCS (both at 250 lM) on sodium channels endogenously expressed in N1E-115 cells, in conditions of fast and slow inactivation of sodium currents. Result: The shift of steady state fast inactivation curves in the hyperpolarizing direction by LCS (-5.13 mV) was twice that by eslicarbazepine (2.38 mV). Eslicarbazepine- and LCS-treated fast-inactivated channels recovered similarly to control conditions. Eslicarbazepine and LCS shifted the voltage dependence of the slow inactivation (V0.5) by -31.2 mV and -53.3 mV, respectively. For eslicarbazepine and LCS, the affinity to the slow inactivated state was 5.9 and 10.4 times higher than to the channels in the resting state, respectively. However, the affinity of LCS (1889 lM) for the channels in the resting state was twice that of eslicarbazepine (3302 lM). For eslicarbazepine and LCS, the time constants for entering the slow inactivated state were 7.00 and 4.54 s, respectively. Conclusion: Both eslicarbazepine and LCS reduce VGSC availability through enhancement of slow inactivation, but LCS demonstrated higher interaction with VGSC in the resting state, with fast inactivation gating and shorter time to enter in the slow inactivated state.
p424 THE DIRECT COSTS OF TREATMENT WITH ANTIEPILEPTIC DRUGS IN BALEARIC ISLANDS M. Massot Cladera, A. Moreno Rojas, C. Barcelo Campomar, I. Barcelo Artigues, I. Chmielewska, A. B. Martinez Garcia, M. Mestre Sanso, and F. J. Molina Martinez Hospital Universitario Son Espases, Palma De Mallorca, Spain
Purpose: The main objective of this study is to determine the direct costs of treatment with antiepileptic drugs (AEDs) in our community. Method: A restrospective analysis from January 2000 to December 2011, was conducted using our epilepsy consultation basedata in Son Espases Hospital to determine the direct costs of antiepileptic treatment. Result: We analyzed 941 epileptic patients with a total of 1396 active treatments, 579 patients receiving monotherapy treatment compared to 362 patients with multiple anti-epileptic drugs (average of 2.9 AEDs). The monthly average cost per patient was 64 (range between 0, 99 to 721). It is possible to distinguish four groups of average costs per drug: average lower than 15 (in which we found the classic AEDs), between 15 to 60 (drugs marked in the nineties), between 60 to 150 (such as Pregabalin, Tiagabine, and Leveticetam) and more than 150, including the newer drugs. The price ranges of the average drugs were between 3, in the case of phenytoin, and 230 for eslicarbacepine acetate. It was determined that the low cost of monotherapy, 48 per drug, compared to 235 in the multiple antiepileptic drugs, was related to the use of the newer and expensive antiepileptics drugs and higher doses of medication. Conclusion: There is a great variability in the direct cost of different antiepileptic drugs. Refractory epilepsy increases the costs due to the newer and expensive antiepileptics drugs and higher doses of medication.
125 Abstracts
Future cost-benefit studies should be used to determine the economic impact of epilepsy treatment and whether their use is justified. HHV-6 DNA detected in 4.7% (6) and HHV-7 DNA detected in 2cases (1.4%) with no correlation with age, sex and clinical signs. Conclusion: HHV-6 & HHV-7 found in 6% of all studied cases. HHV-6 was slightly more frequent thanHHV-7. Our data indicate that herpes viruses is not uncommon causes in children with meningoencephalitis. Our findings presumably may have differed from previous due to epidemiologic and geographic variation (should added to differences in methods, differences in age groups). Its incidence is is lower than other references. Further studies are needed to define the role of HHV-6 and HHV-7 in neurologic disorders especially in immunocompromised hosts.
p425 ASSESSMENT OF ADHERENCE TO MEDICATION IN REFRACTORY PARTIAL EPILEPSY N. Carpentier, J. Jonas, C. Baumann, S. Frismand, J. Vignal, H. Vespignani, and L. Maillard Centre Hospitalier et Universitaire, Nancy, France
Purpose: The adherence to medication (AM) in refractory partial epilepsy (RPE) remains largely unknown. We aimed to directly assess the prevalence of AM in patients with RPE. Method: This prospective observational study screened patients with the diagnosis of RPE, admitted to the Nancy University Hospital between April 2006 and September 2008, and referred for a 5-day pre-surgical evaluation without any antiepileptic drug (AED) tapering. The AM was assessed by the measurement of serum drug level. Two serum samplings for each treatment per patient were performed at day-1 (short-term at home adherence) and day-5 (individual reference concentration). A patient was considered as adherent if he did not have any couple of dosages significantly different. A couple of dosages was significantly different if the day-1 value was inferior (infra-dosed couple) or superior (supra-dosed couple) to at least 20% of the day-5 value. Underconsumers were non-adherent patients with one or more infra-dosed couple. Overconsumers were non-adherent patients with one or more supra-dosed couple, without any infra-dosed couple. Result: Forty-four of the 48 screened patients were included. Nine-teen (43.2%) of the 44 patients were adherent. The clinical characteristics of adherent and non-adherent patients were not significantly different. Eight (32.0%) of the 25 non-adherent patients were underconsumers and seven-teen (68.0%) were overconsumers. Conclusion: The prevalence of AM was poor (43.2%). With a low rate of underconsumers, reconsidering the diagnosis of refractory disease does not appear pertinent in patients with RPE. Surprisingly, the overconsumers are majority. Thus AED dose-dependant adverse effects must be particularly screened in patients with RPE.
p427 EFFECT OF INTERICTAL EPILEPTIFORM ACTIVITIES AND SUBCLINICAL ELECTROENCEPHALOGRAPHIC SEIZURE PATTERNS ON HEART RATE VARIABILITY IN TEMPORAL LOBE EPILEPSY M. Kinoshita*, Y. Demura*, S. Tomita*, R. Matsumoto, and A. Ikeda *National Hospital Organization, Utano National Hospital, Kyoto, Japan; and Graduate School of Medicine, Kyoto University, Kyoto, Japan
Purpose: To investigate whether interictal epileptiform activities and electrographic seizure patterns affect heart rate variability in a patient with temporal lobe epilepsy of bilateral independent foci. Method: Data were obtained from a 45-year-old adult right handed male with lateral temporal lobe epilepsy of bilateral independent foci. Longterm EEG monitoring was performed to evaluate his medically-intractable daily seizures. Electroencephalography (EEG) and electrocardiography (ECG) recorded digitally with sampling rate of 500 Hz for about 60 hours were analyzed. Events of a) EEG seizure pattern lasting more than 3 sec, one side preceding the other by more than 1 sec, and b) unilateral interictal EEG epileptiform activities (spikes, sharp waves, and rhythmic slow activities) during sleep, with inter-event interval of more than 62 seconds, were selected. Heart rate variability indices of high frequency component (HF), low frequency component (LF), and their ratio (LF/ HF), were analyzed using ECG of 30 sec each before and after events. Recording segments with movement or other noise, arousal, and REM sleep were excluded. Result: LF after right-sided interictal events significantly decreased as compared to that before events (p<0.01), and was significantly lower than that after left-sided events (p<0.05). Conclusion: Our data suggest that cardiac sympathetic and parasympathetic modulation can abruptly decrease after interictal epileptiform activities in right temporal lobe.
Neuroimaging and Neurophysiology 4 Tuesday, 02 October 2012

p426 HUMAN HERPES 6, 7-DNAS (PCR) IN CSF OF CONVULSIVE CHILDREN H. R. Monavari, S. Noorbakhsh, and F. Ebrahimi Taj Tehran University of Medical Sciences, Iran, Tehran, Iran
Purpose: Searching the DNA-s of HHV-6 & HHV-7 in CSF samples of convulsive children Method: A cross sectional study (20072009) done in pediatric ward in Rasoul hospital, Tehran Iran. 150 CSF samples obtained from children with convulsion s. Conventional and BACTEC Ped Plus medium; Latex agglutination tests; and in some cases Bacterial PCR assay used. We searched the DNA-s of HHV-6 & HHV-6 quantitavively by Real time PCR in 150 CSF samples obtained from cases. Result: Cases aged between 1180 months, Fever (>38.5) in 74%; Irritability 70%; Convulsion seen in 53% of cases. All Herpes virus detected in 12% (18/150) cases. Both HHV-6 & HHV-7 found in 6% of all cases.
p428 EPILEPSIA PARTIALIS CONTINUA IN CHRONIC AND ACUTE CEREBRAL DISEASE: REPORT OF TWO PATIENTS J. M. Pinzon, P. A. Ruiz, J. J. Ortega, E. Canovas, A. D. Ghinea, and M. De Entrambasaguas Hospital General De Castellon, Castellon De La Plana, Spain
Purpose: Epilepsia partialis continua, described in 1894 by Kozhevnikov, defined as a syndrome characterized by continuous, rhythmic muscular contraction affecting limited part of the body for periods of hours, days or weeks. We found a close relationship with electroencephalogram and MRI findings that support the diagnosis, evolution and localization of clinic.
126 Abstracts
Method: A 41 year old female patient who present myoclonic jerks in left hemifacial in diagnosis of Multiple Sclerosis. A 84 years old female patient, which present myoclonic jerks in left hand in context of a vascular lesion. Both women with electroencephalogram and MRI, present lesion related with the clinic. Result: Patient 1 was a 41 year-old woman with recurring dysarthria and dysphagia for 10 years and negative studies, who was diagnosed of neurological deficit of unknown cause. She presented with a generalized tonic-clonic seizure followed by left hemifacial myoclonic jerks without impaired consciousness. EEG showed PLEDs in center-right parietal region while MRI revealed lesions suggestive of multiple sclerosis. Patient 2 was an 84 year-old woman that presented with acute confusional state followed by continuous myoclonic jerks in her left hand. EEG showed BiPLEDs prevailing in the right hemisphere while CT-scan revealed frontal bilateral hemorrhage with greater volume in the right hemisphere Conclusion: EPC is a syndrome that may be caused by different types of brain injury, either chronic or acute, such as demyelinating inflammatory disease or stroke. EEG and MRI findings show a good topographic correlation to each other and to symptoms as well. epilepsy (left and right-sided epileptic foci) manifested by focal seizures with secondary generalization as compared with depakine effect and control group. Method: Three groups of epilepsy patients and control group were administered neuropsychological and cognitive tests for psychic and frontal lobe functions, and others. The 1 and 2 groups included patients with symptomatic frontal lobe epilepsy with focal secondarily generalized seizures (left and right-sided foci, 79 and 74 subj.) All patients had a medication change from DPA to TPM. They were free from seizures and had medium TPM dosage of 200 mg/day. The patients of 3 group had the same form of epilepsy and had long-term VPA therapy without withdrawn, mean DPA dosage of 400 mg/day (162 subj.). The statistical intergroup comparisons were analysed for all tests. The statistically significant differences on measures of phychic functions and frontal lobe associated functions were obtained for groups of patients and control. Higher scores in cognitive performance and tests for frontal lobe associated functions were obtained in 1 and 2 TPM groups as compared the VPA group. Result: Results demonstrate also the more distinct improvement (P<0.01) in patients of the TPM-1 group with left-sided foci in frontal areas as compared the TPM-2 and DPA groups: in scores for temporal ordering, sorting of cards, synthesis, depression, planning and control functions, etc. Conclusion: The results helps to elucidate the contradictory data concerning to cognitive effects of topamax.
p429 THE ROLE OF STREPTOCOCCAL INFECTION IN CHILDREN WITH NEUROPSYCHIATRIC MANIFESTATIONS (PANDAS): A CASE CONTROL STUDY E. Shirazi, S. Noorbakhsh, and F. Ebrahimi Taj Tehran University of Medical Sciences, Iran, Tehran, Iran
Purpose: To compare the serum antibodies against group A streptococcus between cases with OCD &ADHD (pediatric autoimmune psychiatric disorders) and control group Method: A cross sectional/cases control study in peadiatric psychology clinics in Tehran (Rasoul Hospital) during 20072010 had done. We compare serum group A streptococcal antibody titers (streptolysin O, deoxyribonuclease B, and Streptokinase) between 79 cases with OCD/ ADHD disorder and 39 control group. Result: Most of cases studied in summer (57%) and spring (23%). Three type of antibodies were higher in cases (p=0.000). ASOT: cut off level 195 had 90% sensitivity; 82% specificity, PPV 92%; AUC: (CI= %95; 0.990.91) Anti streptokinase: cut off level 223 had 82% sensitivity; 82% specificity PPV 95%; AUC: (CI= %95; 0.9340.735) Anti DNase: cut off level 140 had 82% sensitivity; 82% specificity PPV 95%; AUC: (CI= %95; 0.990.91) Conclusion: Most of cases studied in summer (57%) and spring (23%) 0.3 type of antibodies were higher in cases (p=0.000). ASOT: cut off level 195 had 90% sensitivity; 82% specificity,PPV 92%; AUC: (CI= %95; 0.990.91) Anti streptokinase: cut off level 223 had 82% sensitivity; 82% specificity PPV 95%; AUC: (CI= %95; 0.9340.735) Anti DNase: cut off level 140 had 82% sensitivity; 82% specificity PPV 95%; AUC: (CI= %95; 0.990.91)
p431 DIFFERENCES OF INTRACEREBRAL ELECTRICAL STIMULATION THRESHOLDS IN THE HUMAN BRAIN C. Stephani*, and M. Z. Koubeissi *University Medical Center Goettingen, Goettingen, Germany; and UH Medical Center, Cleveland, USA
Purpose: Differences in threshold current intensities between cortical surface and intracortical stimulation have been recognized repeatedly. We additionally demonstrate differences between cortical and subcortical stimulation thresholds in humans. Method: 5 female patients (mean age 40.2 years) with intractable focal epilepsy underwent invasive presurgical epilepsy monitoring. Three depth electrodes with 1012 electrode contacts each were implanted tangentially into the patients insular lobes (2 left, 2 right, 1 bilateral) leaving half of the electrode contacts on average in the white matter above the insula. Electrode contacts were stimulated electrically until a clinical response was produced (current intensity 1.514 mA, frequency 50 Hz, pulse width 0.3 msec, and train duration 35 seconds). For localization of electrode contacts, postsurgical cranial computer-tomography was superimposed onto presurgical magnetic resonance imaging using fiducial markers (Software: iplanstereotaxy 2.6). Result: 118 electrodes contacts elicited reproducible symptoms upon electrical stimulation in the absence of afterdischarges. The mean stimulation threshold of 45 electrode contacts clearly located in grey matter (92 mA), which produced somatosensory, viscerosensory and gustatory responses was significantly higher than that of the 48 electrode contacts located in the white matter (5.22.9 mA), which produced somatosensory or motor symptoms (t-test: p = 6.98 -11). Conclusion: Stimulation thresholds necessary to induce symptoms in insular grey matter are significantly higher compared to stimulation thresholds in the suprainsular white matter. This may be due to a concomitant counteractivation of inhibitory as well as excitatory neuronal elements with intracortical stimulation which we do not expect in case of subcortical stimulation.
p430 COGNITIVE FUNCTIONS IN PATIENTS WITH FRONTAL LOBE EPILEPSY DURING TOPIRAMATE OR DEPAKINE THERAPY G. V. Selitskii, and N. Sorokina Moscow Medical Stomatological Unuversity, Moscow, Russian Federation
Purpose: The study was aimed to analyse the cognitive effects of new antiepileptic drugs topamax in patients with symptomatic frontal lobe
127 Abstracts
p432 THALAMOCORTICAL DYSRHYTHMIA IN PHOTOSENSITIVE EPILEPSY D. Brazzo*, G. Di Lorenzo, and S. Seri* *Aston University, Birmingham, UK; and University of Rome Tor Vergata, Rome, Italy
Purpose: To provide experimental support to the hypothesis of a possible disruption in the physiological thalamic regulation of cortico-cortical synchronisation - thalamocortical dysrhythmia (TCD) - in the pathophysiology of photosensitive epilepsy (PSE). Method: 16 subjects, 8 with PSE and 8 healthy volunteers (CTR) with no history of neurological disorders entered the study. Data was acquired with a 128-channel dense array EEG and a 306 sensor MEG. Horizontal stationary sinusoidal gratings with spatial frequency of 3 cycles per degree (cpd) were presented for a 4 sec on period, followed by a 4 sec off period during which a full field equiluminant screen was shown. Independent Component Analysis (ICA) and time-frequency analysis of the extracted components were carried out, followed by cluster analysis on the components map. Result: Clusters of components with clear dipolar pattern in the occipital region exhibited the following features: 1- evoked and induced gamma band (2560 Hz) in PSE and CTR groups, without statistically significant differences between the two groups; 2- sustained desynchronisation in the alpha- beta bands (820 Hz) only in the CTR group; 3- statistically significant phase locked and sustained synchronisation (power increase) in the theta band (48 Hz) in the PSE group. Conclusion: Abnormal theta synchronisation can be interpreted as the electrophysiological correlate of disordered connection between thalamus and occipital cortex in PSE, in line with TCD model. TCD rather than a syndrome, as proposed in several studies, could be a shared mechanism in a number of pathological conditions including PSE. months post-op - pre-op: significant increase in right PFC activity with a significant reduction in bilateral HC activation was seen in patients compared to controls. 12 months post-op - pre-op: significant increase in bilateral posterior hippocampal activation (predominantly right) with a significant decrease in left PFC activation was seen in patients compared to controls. Conclusion: The memory encoding network following L ATLR displays dynamic plasticity effects. By 4 months a relative increase of right PFC activation and suppression of HC activation is observed. Subsequent to this period, re-emergence of HC activity occurs bilaterally with diminution of left PFC activation.
p434 FUNCTIONAL AND STRUCTURAL CONNECTIVITY OF WORKING MEMORY NETWORKS IN TEMPORAL LOBE EPILEPSY G. P. Winston*, J. Stretton*, M. K. Sidhu*, C. Vollmar, M. Symms*, P. J. Thompson, and J. Duncan* *Epilepsy Society MRI Unit & UCL Institute of Neurology, London, UK; University of Munich, Munich, Germany; and UCL Institute of Neurology, London, UK
Purpose: To determine the underlying network architecture of disrupted working memory (WM) networks in temporal lobe epilepsy (TLE) using functional and structural connectivity analyses. Method: 84 subjects (30 controls, 30 LHS, 24 RHS) underwent visuospatial WM fMRI and DTI. fMRI revealed six key WM nodes - bilateral Middle Frontal Gyrus (MFG), Superior Parietal Lobe (SPL) and hippocampi. Functional connectivity: the extracted time-series from the peak voxel of each node in each subject was used as a regressor in a further general linear model fMRI analyses to determine areas functionally coupled with each node. Structural connectivity: tractography was seeded from the segmented nodes in each subject and the total volume of connectivity was determined for each subject. Result: Functional connectivity In LHS, seeding from the bilateral SPL and left MFG showed increased connectivity to the left hippocampus. In RHS, seeding from bilateral MFG and SPL showed increased connectivity to the right post-central gyrus. Seeding from the hippocampi, both LHS and RHS showed increased temporo-temporal connectivity bilaterally. Structural connectivity In LHS and RHS, there was an increased volume of connectivity from the ipsilateral SPL and hippocampus with a trend to increase on the contralateral side. Conclusion: In a task which requires the activation of the fronto-parietal nodes and simultaneous deactivation of the hippocampus, LHS patients show increased functional and structural coupling between parietal and temporal nodes. RHS patients exhibit a similar pattern structurally but with increased functional connectivity to right central motor regions. Together these results indicate hyperconnectivity of the fronto-parietotemporal WM network in TLE.
p433 IMAGING DYNAMIC MEMORY ENCODING NETWORK PLASTICITY POST ANTERIOR TEMPORAL LOBE RESECTION FOR REFRACTORY TEMPORAL LOBE EPILEPSY M. K. Sidhu*, J. Stretton, G. P. Winston, S. Bonelli, M. Symms, P. J. Thompson, M. Koepp, and J. Duncan *Epilepsy Society MRI Unit & UCL Institute of Neurology, London, UK; UCL, London, UK; and Institute of Neurology, London, UK
Purpose: An intact fronto-temporal interaction is necessary for successful memory encoding. Patients with TLE have a material specific episodic memory loss that can be compounded by anterior temporal lobe resection (ATLR). We investigated the episodic memory network in left TLE (LTLE) patients pre and post ATLR to determine plasticity of the network. Method: 13 patients with unilateral LTLE performed an fMRI memory encoding paradigm of words and faces preoperatively (pre-op) and 4 and 12 months post standard ATLR (post-op). 13 controls were scanned at equal intervals to patients. fMRI analysis was performed with SPM8. Result: Preoperative Word encoding: controls activated the left prefrontal cortex (PFC) and hippocampus (HC) whilst LTLE patients showed additional right PFC and HC activation. Face encoding: controls activated the right PFC and bilateral HC whilst LHS patients showed right PFC and HC activations only. Postoperative No material specific effect was seen therefore faces and words analyses were combined. 4
p435 MECHANISM OF ACTION OF VAGAL NERVE STIMULATION; EVIDENCE FOR ACUTE ANTI-SEIZURE AFFECT C. Mcgrane, F. Kazi, L. Flores, K. N. Ramesha, C. Quelly, M. P. Richardson, C. E. Polkey, and R. D. Elwes Kings College Hospital, London, UK
Purpose: To assess whether vagal nerve stimulation (VNS) acutely affects the frequency or duration of electrical seizures in adults.
128 Abstracts
Method: Nine adult patients with frequent electrical seizures (usually fast activity) were identified from the cases attending the VNS clinic at King's College Hospital. The frequency and duration of ictal activity was measured by visual inspection of the raw EEG during prolonged monitoring. Total numbers of seizures and ictal activity in seconds per minute were compared during a minimum of 10 on/off cycles. Statistical significance was assessed using non parametric tests for paired and unpaired observations. Result: All cases showed a reduction in mean seizure duration during on periods compared to off periods of VNS. The reduction ranged from 6% to 33% in 4 cases (not significant.) In a further five the reduction ranged from 63% to 99% (p=0.001 to p=0.004). Seizure frequency during on an off periods showed either small increases or decreases, none of which reached significance; one patient had a total of 12 seizures during 72 on/ off cycles in which 11 occurred during off periods. Conclusion: In a selected group of patients with frequent electrical seizures VNS on periods were associated with reduction in mean seizure duration in all cases, which was marked in five. Seizure frequency was not affected. The changes suggest that neural stimulation may acutely alter mechanisms of seizure spread or termination.
p437 SLEEP IN PARTIAL EPILEPSY (PE) AS COMPARED TO IDIOPATHIC GENERALISED EPILEPSY (IGE) J. M. Boserio*, R. Bradbury*, Z. Thayer*, Z. Fitzgerald, and A. Mohamed *Royal Prince Alfred Hospital, Sydney, NSW, Australia; Macquarie University, Sydney, Australia; and University of Sydney, Sydney, NSW, Australia
Purpose: The current study aims to compare sleep variables in patients with PE and IGE. Method: We retrospectively reviewed 22 patients with epilepsy who underwent prolonged Ambulatory EEG (AEEG) for 4 consecutive nights, from August 2009 July 2010. A 21 channel EEG and ECG was performed according to the 1020 system. Sleep was scored over the first 24 hour period by three trained EEG technicians using Profusion PSG3 software (Abbotsford, Australia) based on the updated American Academy of Sleep Medicine Manual for Scoring Sleep and Associated Events (Iber, Ancoli-Israel, Chesson and Quan, 2007). All subjects were outpatients with stable doses of medications. Patients were grouped as those with PE (n=15) or IGE (n=7). We measured durations of Stages I-IV NREM sleep, duration of REM sleep, daytime naps, inter-ictal epileptiform discharges (IEDs) during sleep and sleep efficiency. The IEDs in sleep were counted and grouped into zero, infrequent (<10 in sleep) and frequent (10 in sleep). Chi squared analysis and one-way ANOVA was carried out using PASW Statistics version 18.0. Result: We found no strong relationships between the measured sleep variables when comparing patients with PE vs IGE. The average sleep efficiency was 85% and 89% for the groups respectively (p=0.4) which is within normal limits. The duration of Stage IV NREM sleep was significantly longer in patients with IGE (f=4.4, df 1, p=0.05). Conclusion: In our cohort, there were no significant differences in the measured sleep variables and sleep efficiency in patients with PE vs IGE.

p436 THE SIGNIFICANCE OF INTRA-STIMULATION DISCHARGES DURING NEUROPHYSIOLOGIC LANGUAGE MAPPING FOR EPILEPSY SURGERY I. Karakis*, B. Leeman, C. Leveroni*, R. R. Kilbride*, S. Cash*, E. N. Eskandar*, and M. V. Simon* *Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; and Emory University, Atlanta, GA, USA
Purpose: Intra-stimulation discharges (IDs) can occur during language mapping via low frequency electrical stimulation. They are largely unrecognized due to the significant stimulus artifact associated with this method, and may precede the occurrence of after-discharges (ADs). The latter can self-propagate beyond the stimulation epoch and organize in seizures. This study intends to identify predictors of IDs occurrence and determine whether the latter increases the probability of triggered ADs. Method: 333 stimulation events performed during language mapping, were analyzed in 3 patients who underwent intracranial EEG recording. IDs were identified in 77 events. Multivariate logistic regression analysis was used to study the relationship of IDs relative to the stimulus current intensity, stimulation duration, its lobar location and its proximity to regions of abnormal cortical excitability (as characterized by presence and frequency of baseline epileptiform discharges-BEDs). Result: Presence of BEDs in close proximity to stimulation, increase in stimulus intensity by 1 mA and in stimulation duration by 1 second independently increase the odds of triggering IDs 7.4 times (OR=7.4, CI95 [2.83, 19.33], p<0.0001), 1.37 times (OR=1.37, CI95 [1.18, 1.57], p<0.0001) and 1.39 times (OR=1.39, CI95 [1.19, 1.62], p<0.0001) respectively. Higher frequency of BEDs and lobar location of stimulation have no effect. Occurrence of IDs increases the odds of triggering ADs 5 times (OR=5.02, CI95 [2.47, 10.2], p<0.0001). Conclusion: Longer stimulations, higher currents and presence of BEDs at the stimulation site, increase the probability of IDs occurrence. The latter increases the probability of triggering ADs. Attention to IDs may improve safety and precision of neurophysiologic mapping.
p438 AFTER-DISCHARGE GENERATION AND TERMINATION DURING FUNCTIONAL STIMULATION IN CHILDREN J. Pocock*, H. Cross*, S. Boyd, W. F. Harkness, and R. M. Pressler *Great Ormond Street Hospital for Children NHS Trust, London, UK; and Great Ormond Street Hospital for Children, London, UK
Purpose: Functional cortical stimulation (CS) during invasive pre-surgical evaluation for epilepsy surgery is used for clinical localization purposes but can generate afterdischarges, which may evolve into clinical seizures. Brief pulses of stimulation (BPS) can terminate afterdischarges in adults. The aim of this study was to evaluate the effectiveness and safety of BPS in children. Method: Children undergoing CS with subdural electrodes were monitored for afterdischarges. BPS were administered within 13 sec of occurrence at primary side (same intensity and electrical characteristics, same pair of electrodes as CS, reduced duration of 0.5 sec). Duration of afterdischarges were compared to a control group (no-BPS) using survival curve analysis and log-rank test. Result: Afterdischarges and effect of BPS were analysed in 14 children (14 in the BPS and 7 in the no-BPS group). A total of 5005 stimulations were carried out, provoking trains of afterdischarges in 17.5% in the BPS group and 17.5% in the no-BPS group. These provoked clinical seizures in 0.6% of afterdischarges. A total of 597 BPSs were administered to terminate afterdischarges in addition to 97 BPSs given inadvertently. BPS
129 Abstracts
proved no seizures or any other adverse reactions. BPS reduced post-BPS duration of afterdischarges significantly (p less then 0.001) in comparison with the control group Conclusion: Brief pulse stimulation is a safe and effective method in terminating afterdischarges generated by cortical stimulation in children undergoing invasive monitoring. in 4 seizures and markedly enhanced in 5 seizures. These included: Marked alpha asymmetry in 13% of all seizures, regional slowing in 13% and regional or lateralised epileptiform activity in 10%. In three patients (15%) those were the only lateralising EEG features. In 16 patients at least one seizure from wakefulness occurred. 6/23 (26%) seizures from wakefulness were followed by sleep; EEG seizure duration was comparable whether sleep occurred or not (26 vs 29s). Conclusion: Careful EEG analysis of the postictal state added unique information in a significant number of patients and should be explored systematically in this challenging group. Even daytime seizures are followed by postictal sleep in a significant proportion, adding to disruption of daytime activities.
p439 HOW FREQUENT ARE ADDITIONAL EPILEPTOGENIC ABNORMALITIES DETECTED?: INPATIENT LONG-TERM EEG MONITORING VS. OUT-PATIENT EEG K. A. Siddiqui, E. Khalid, and S. Sinha National Neurosciences Institute, King Fahad Medical City, Riyadh, Saudi Arabia
Purpose: Out-patient EEG (opEEG) study, which is of duration of <1 hour, is about 3050% sensitive in picking up epileptogenic abnormalities. Even if they pick up abnormalities, still it is possible that the patient may have additional abnormalities that can affect the diagnosis and subsequent management of the patient. We intend to study the frequency of additional epileptogenic abnormalities seen with inpatient long-term EEG monitoring (ltEEG) that were not picked by outpatient study. Method: We obtained data on consecutive patients who were referred with diagnosis of seizure disorder, and compared their opEEG study performed in the EEG lab to ltEEG records from the Epilepsy monitoring unit. We also looked at demographics and mean duration of epilepsy. Result: Sixty-eight patients, 35 males and 33 females with mean (+ SD) age 24 (+10.5) years and duration of epilepsy 10.3 (+9.6) years were recruited. In 56% (n=38), ltEEG provided new information as compared to the opEEG. Amongst these, 17 patients, whose outpatient study was abnormal, had additional epileptogenic abnormalities on ltEEG. These abnormalities were focal (n=15), and generalized discharges (n=2) that were not present in the opEEG. Forty four percent (n=30) had similar findings in both studies. Conclusion: Long-term EEG revealed 25% additional epileptogenic abnormalities missed by out-patient EEG study that may be useful in clinical decision making and optimal management of the patient.
p441 PRELIMINARY RESULTS OF VIDEO-EEG FINDINGS IN THE NEURO-INTENSIVE CARE UNIT: IS THERE A PROGNOSTIC SIGNIFICANCE IN ACUTE STROKE? N. Dericioglu*, E. M. Arsava, and M. A. Topcuoglu *Hacettepe University Institute of Neurological Sciences and Psychiatry, Ankara, Turkey; and Hacettepe University, Ankara, Turkey
Purpose: A considerable number of acute stroke patients are followed up in neuro-intensive care units. Epileptiform discharges and non-convulsive status epilepticus (NCSE) are not infrequent findings. In our study we aimed to determine the characteristics of EEG findings and the frequency of NCSE. We also looked whether these findings were correlated with the patients prognosis. Method: We analyzed retrospectively the EEG data of patients with ischemic stroke (IS) or hemorrhagic stroke (HS), who had video-EEG monitoring in our center during November 2009-February 2012. EEG findings were: epileptic discharges (ED), triphasic waves (TW) and frontal intermittent rhythmic delta activity (FIRDA). These findings were correlated with the patients modified Rankin scale (mRS) score at discharge. Result: 41 patients (14 M, 27 F; age: 2690) were included. 26 patients had IS, 11 had HS and 4 had IS + HS. EEG findings were: ED in 9 (6 IS, 3 HS); TW in 8 (4 IS, 2 HS, 2 IS + HS) and FIRDA in 5 patients (3 IS, 2 HS). NCSE was diagnosed in 3 patients (7.3%) (2 IS, 1 HS). At discharge, mRS score was 56 in 29 patients. All the EEG characteristics described above were detected only in patients with mRS score 56. One patient with NCSE died, in the rest the mRS score was 0 and 5. Conclusion: ED, TW or FIRDA were detected only in patients with the poorest prognoses. All the described EEG patterns were present in both IS and HS. NCSE was rare and did not correlate with outcome.
p440 THE POSTICTAL STATE IN DAYTIME FRONTAL LOBE SEIZURES: EEG AND BEHAVIOURAL CHARACTERISTICS K. Whitehead*, H. Millward*, C. Scott*, S. Eriksson*, and B. Diehl *National Hospital of Neurology and Neurosurgery, London, UK; and UCL Institute of Neurology, London, UK
Purpose: To assess postictal sleep following daytime seizures in frontal lobe epilepsy (FLE), and presence of additional lateralising features of the postictal EEG. Method: We included patients with unilateral FLE based on semiology, EEG and either presence of a lesion on MRI or intracranial recordings. Seizures with objective clinical signs (loss of awareness, disruption of body posture) between 8am and 8pm were included. Postictal EEG analysis of one hour was performed and presence of stage II sleep noted. Result: We included 31 seizures in 20 patients (15 left, 5 right FLE). Seizure semiology was characterised by motor manifestations as main feature in 19, and subtle automatisms with alteration of awareness in 12 seizures. In 9 seizures (29%) the postictal EEG showed lateralising features concordant with the ictal onset zone, not seen in the interictal EEG
p442 NOONAN'S SYNDROME AND EPILEPSY. NEUROPHYSIOLOGICAL FINDINGS N. Torres Cao, P. Giner Bayarri, K. M. Quintero Hernndez, J. Moliner Ibez, R. Faus Cerd, M. R. Chilet Chilet, A. Mazzillo Ricaurte, M. Escudero Torrella, and S. Garca Moreno Dr. Peset Hospital, Valencia, Spain
Purpose: Noonan's syndrome is a genetic disorder which was described in 1963, it has a prevalence of 1/2500 newborns and it is characterized by the distinctive facial phenotype, cardiac defects, failure to thrive and neurological symptoms as cognitive deficit, Arnold Chiari malformation and epilepsy, which is also associated to behavioural and attentional disorders. In this study we try to describe the neurophysiological findings and the characteristics of the seizures in Noonan's syndrome.
130 Abstracts
Method: We revise the cases of patients with Noonan's syndrome which have been studied in our epilepsy unit and the performed complementary explorations. Result: Epileptic seizures are commonly unnoticed in Noonan's syndrome, and due to its association with behavioural disorders it is especially important to perform electroencephalograms for the diagnosis and control of the seizures. We present electroencephalogram images in patients with Noonan's syndrome who present seizures with a poor control, which show focal paroxysmal activity. Conclusion: The electroencephalogram allows us to find subclinical paroxysmal activity in patients with this syndrome and helps us to achieve a better clinical management of the patients. (VN-EP) during implantation of the VNS Therapy system. We discuss the significance of measuring VN-EP in VNS Therapy. Method: We measured VN-EP in 25 patients who underwent implantation of VNS system. After induction of general anesthesia, scalp EEG electrodes were set. After placing the VNS lead around the left vagus nerve, VN-EP was recorded while adjusting the stimulation parameters and adjusting the location of the VNS lead on the nerve. Recordings were made before and after administration of a muscle relaxant. Result: A reproducible positive peak around 3.4 msec was detected in A1-Cz in all patients, which remained in muscle relaxation. Meanwhile no significant early peaks were detected in A2-Cz, C3-Cz, or C4-Cz. The latency of the peak was shortened by moving the lead rostrally. Although high-amplitude EPs after 10.0 msec were detected in many channels, all signals disappeared in muscle relaxation. Conclusion: This study is the first to demonstrate direct evidence of upward propagation of vagus nerve impulses in the clinical setting with VNS Therapy. The recording of VN-EP provides basic information on electrophysiological properties of the vagus nerve and serves as confirmatory evidence for appropriate placement of the VNS lead during surgery. Furthermore, if the recording in the awake setting is established, they may serve as a surrogate marker of upward stimulation during VNS Therapy.
p443 INTER- AND INTRA-RATER RELIABILITY OF EEG INTERPRETATION: A LARGE, SINGLE-CENTER STUDY S. G. Abdel-Baki*, A. Omurtag*, J. Weedon, C. A. Lushbough, G. Chari, E. Koziorynska, D. Maus, T. Mcsween, K. A. Mortati, A. Reznikov, V. Arnedo, and A. C. Grant *Bio-Signal Group, Brooklyn, NY, USA; SUNY Downstate Medical Center, Brooklyn, NY, USA; and SUNY Downstate, Brooklyn, NY, USA
Purpose: To assess inter-and intra-rater reliability of EEG interpretation utilizing a large sample of heterogeneous EEGs. If EEG reliability is not sufficiently high, the utility of EEG as a diagnostic tool is limited. Method: We performed a large study of EEG inter- and intra-rater reliability. Six board-certified EEGers interpreted 300 representative EEGs (knowing only patient age and medications) divided between two interpretation time intervals (T1 and T2), separated by several months. Each EEG was interpreted by 3 readers. Each reader interpreted 100 EEGs at both T1 and T2, 150 of which were unique. EEGers were unaware that 50 EEGs per reader interpreted at T1 were reinterpreted at T2. For each EEG, readers assigned probabilities to one or more diagnostic categories (normal, status epilepticus, seizure, epileptiform + slowing, epileptiform only, slowing only, uninterpretable) with one category assigned a higher probability than any other. Cohen's kappa coefficient (jc) was used to measure within-rater agreement. Result: Intra-rater jc ranged from 0.33 to 0.73 for individual readers, with an aggregated jc of 0.59 (95% CI 0.523 0.653). jc for rater pairs (inter-rater reliability study) ranged from 0.29 to 0.64 with an aggregated Fleiss kappa of 0.44 (95% CI 0.395 0.504). Conclusion: EEG inter- and intra-RR are in the weak to good range for highly qualified and experienced EEGers. The subjectivity of EEG interpretation may be reduced by establishing consensus interpretation guidelines, developing statistical prediction rules, and engaging neurologists in an on-line continuous review of challenging studies with the goal of achieving consensus interpretations. Supported by NIH 1RC3NS070658.
p445 VITRUAL HUMAN PHYSIOLOGY - A SIMULATION TECHNIQUE TO VISUALISE ICTAL CARDIAC RHYTHUM S. Narula Post Graduate Institute of Dental Sciences, Rohtak, India
Purpose: It is proposed to have Virtual Human to facilitate Multi scale modeling to simulate Pathophysiology of Cardio-Vascular, Respiratory and Autonomic nervous system by using Software, working station and workflow. Method: Several studies have assessed the frequency and character of ictal cardiac rhythm during seizures, and the most compelling evidence derives from the presence of ictal arrhythmias. When ictal cardiorespiratory variables were recorded in people with epilepsy, an increase in heart rate in 91% of seizures and a transient bradycardia in five seizures (four patients) were found. Another study evaluated the eletrocardiographic (ECG) changes during seizures in patients with refractory epilepsy. This showed that 70% of patients had either ECG abnormalities (16%), tachycardias (30%), or both (23%) during the ictal and/or post-ictal period. Result: As it is routinely difficult to perform these investigations, it is hereby proposed virtual human physiology sample as ictal patient to extract information, apply it clinically and prevent complications up to SUDEP Conclusion: The proposed technique is expected to predict SUDEP in Epileptic Patients.
p444 VAGUS NERVE EVOKED POTENTIAL IN VAGUS NERVE STIMULATION THERAPY -METHOD AND CLINICAL APPLICATION K. Usami*, K. Kawai*, M. Sonoo, and N. Saito *The University of Tokyo, Tokyo, Japan; Teikyo University Hospital, Tokyo, Japan; and The University of Tokyo Hospital, Tokyo, Japan
Purpose: There has been no direct marker to verify the afferent propagation of nerve impulses in vagus nerve stimulation (VNS) Therapy. We established a method for recording the vagus nerve evoked potential

p446 DTI-BASED EVIDENCE FOR IMPAIRED INTEGRITY OF MAJOR WHITE MATTER TRACTS IN NON-LESIONAL TEMPORAL LOBE EPILEPSY C. Whelan*, S. Alhusaini*, J. F. M. Meany, G. Boyle, A. Fagan, M. Fitzsimons, E. OHanlon, C. Doherty, N. Delanty, and G. L. Cavalleri*
131 Abstracts
*Royal College of Surgeons in Ireland, Dublin 2, Ireland; St. James's Hospital, Dublin 8, Ireland; and Beaumont Hospital, Dublin 9, Ireland
Purpose: Here we employ a series of diffusion tensor imaging (DTI) techniques to investigate, using a case/control design, potential structural changes within six major white matter tracts of the brain in non-lesional temporal lobe epielpsy (nl-TLE). The tracts studied were the corpus callosum, superior and inferior longitudinal fasciculi, anterior commissure, corticospinal tract and uncinate fasciculus. Method: Scans were acquired using a 3 Tesla Phillips Achieva platform at St. James's Hospital, Dublin and processed using two software packages: Explore DTI (to apply deterministic fiber tractography to our data) and Tract-Based Spatial Statistics (TBSS - a voxelwise, permutationbased algorithm which measures fractional anisotropy (FA)). Result: Deterministic tractography using ExploreDTI revealed significant thinning of the white matter fibers of the corpus callosum in nl-TLE patients (p<0.005; Bonferroni-corrected), in addition to significant reductions in the length and volume of uncinate fasciculus fibers in nlTLE (p<0.05; Bonferroni-corrected). Tractography further revealed significant FA reductions in the uncinate fasciculus, left superior longitundal fasciculus, right inferior longitudinal fasciculus and anterior corpus callosum of nl-TLE patients compared to healthy controls (p<0.05; Bonferroni-corrected). TBSS results confirmed these FA reductions illustrating significantly impaired white matter integrity in widespread regions of the left superior and right inferior longitudinal fasicucli and genu of the corpus callosum; with additional FA reductions in the corticospinal tract, somatosensory cortex and thalamus (p<0.05). Conclusion: Detected white matter changes in non-lesional temporal lobe epilepsy patients may be related to brain malformations leading to the development of epilepsy, or alternatively could be secondary to seizure generalization/propagation. Conclusion: This study provides evidence for impaired experiencerelated learning in JME patients still suffering from seizures. None of our patients experienced any seizures during testing, which suggests that inter-ictal, or seizure-related network dysfunction might impair the ability to learn. FMRI points to hyperactivity of the dorsolateral prefrontal cortex as the neuroanatomical correlate of this dysfunction.
p448 NON-INVASIVE LANGUAGE MAPPING IN EPILEPTICS AND IN BRAIN TUMOR PATIENTS M. Genetti, F. Grouiller, S. Vulliemoz, L. Spinelli, M. Seeck, C. Michel, and K. Schaller University Hospital of Geneva, Geneva, Switzerland
Purpose: To establish a single, short functional MRI (fMRI) task that reliably localizes crucial language areas in individual patients. Method: fMRI was measured during a 8-minute auditory semantic decision task in 18 subsequently operated patients suffering from focal epilepsy or from brain tumor as well as in 28 healthy controls. Group and individual analyses were performed and compared to the Wada test, electrocortical stimulation and post-surgical language outcome. Result: The group analysis revealed a lateralization index of 82 for the controls and 46 for the patients. In the controls, BOLD clusters concordant with Broca and Wernicke's areas were activated in 96% and 89% respectively using very conservative thresholding. Activation was more heterogeneous in the patients but Broca and Wernicke's areas were still activated in 83% and 89% of the patients, respectively. fMRI results overlapped with electrocortical stimulation in three implanted patients and with the Wada test in all patients in whom it was performed. Transient post-surgical language deficits were found in patients in whom surgery was performed in the vicinity of the fMRI activations or who had post-surgical complications implicating areas of fMRI activations. Conclusion: The proposed fast fMRI language protocol not only correctly lateralized, but reliably localized the most relevant language areas in individual subjects. It offers increased security during surgical planning and during image-guided resection of epileptogenic foci, and of brain tumors.
p447 THE IOWA GAMBLING TASK IN JUVENILE MYOCLONIC EPILEPSY B. Wandschneider*, M. Centeno*, C. Vollmar, J. OMuircheartaigh, A. Haag*, J. Stretton*, V. Kumari, B. Schmitz, G. J. Barker, M. P. Richardson, P. J. Thompson*, J. Duncan*, and M. Koepp* *UCL Institute of Neurology, London, UK; University of Munich, Munich, Germany; King's College London, London, UK; and Vivantes Humboldt Klinikum, Berlin, Germany
Purpose: Patients with Juvenile Myoclonic Epilepsy (JME) are thought to be impulsive, unable to learn from previous experience, and often present with risk-taking behaviour, suggestive of frontal lobe dysfunction. We investigated impulsivity in JME and healthy controls using the Iowa Gambling Task (IGT) to characterize decision-making behaviour. Method: 21 JME patients and 11 controls, comparable for gender and verbal IQ, were assessed with the IGT. Subjects chose from four decks of cards with a total 100 cards split into five blocks of 20 (deck A and B indicative of high risk, C and D of low risk behaviour). A correlation of IGT performance and network activation during a functional MRI (fMRI) working memory task was performed with SPM-5. Result: Advantageous minus disadvantageous choices (C+D-[A+B]) were established. Both groups learned throughout the task (last versus first block: JME: p=0.001; controls: p=0.009). Post-hoc analysis revealed more learners in the seizure-free group (Pearsons Chi-square p=0.040). In controls, poorer IGT performance was associated with decreased deactivation of the default mode network. In JME, poorer performance was associated with increased pre-frontal cortex activation (p<0.001 uncorrected).
p449 BRAIN P-GLYCOPROTEIN FUNCTION STUDIED IN RATS WITH TWO NOVEL PET RADIOTRACERS: [11C]QUINIDINE AND [11C]LANIQUIDAR. DIFFERENCES BETWEEN CONTROLS AND EPILEPTIC RESPONDERS AND NON-RESPONDERS R. A. Voskuyl*, S. Syvnen, V. Russmann, J. Verbeek, J. Eriksson, R. Schuit, A. D. Windhorst, M. Labots, M. Rongen, A. A. Lammertsma, E. C. De Lange, and H. Potschka *SEIN Epilepsy Institutes of The Netherlands Foundation, Heemstede, The Netherlands; Leiden/Amsterdam Center for Drug Research, Leiden, The Netherlands; LudwigMaximilians-University, Mnchen, Germany; and VU Medical Center, Amsterdam, The Netherlands
Purpose: To characterize brain pharmacokinetics of P-gp substrate [11C]quinidine and P-gp inhibitor [11C]laniquidar in naive rats and in a chronic rat model of epilepsy, before and after treatment with P-gp inhibitor tariquidar.
132 Abstracts
Method: Twenty-two rats, divided into controls, responders and nonresponders to phenobarbital, underwent scans with both [11C]quinidine and [11C]laniquidar of 45 minutes duration each. All rats were treated with 15 mg/kg tariquidar before a second scan with both radiotracers. Brain pharmacokinetics were studied using Logan graphical analysis with plasma input to yield estimates of VT (brain-to-blood partition coefficient). Result: [11C]quinidine and [11C]laniquidar brain concentrations were very low at baseline. After tariquidar treatment the concentrations increased 3-fold and 9-fold for [11C]quinidine and [11C]laniquidar. VT estimates of [11C]quinidine, were 0.8 mL mL-1 min-1 and 3 mL mL-1 min-1 before and after P-gp inhibition. [11C]quinidine concentrations were higher in non-responders than controls and responders, while [11C]laniquidar brain concentrations where increased in epileptic animals compared to controls. [11C]quinidine metabolised fast: 25 minutes after injection only 15% and 21% of intact [11C]quinidine was present in brain and plasma. For [11C]laniquidar these values were 55% and >75%. Conclusion: Both [11C]quinidine and [11C]laniquidar brain concentrations increased after tariquidar treatment. Although described as inhibitor, [11C]laniquidar appeared to be a strong P-gp substrate. Epilepsy had only a small influence on brain concentrations of both radiotracers. Intriguingly, previous studies with quinidine showed that total brain concentration in epileptic rats increased 40-fold after tariquidar, suggesting a complex P-gp sensitive redistribution after brain entry in epileptic rats. Method: Design: Retrospective review. We analyzed all the seizure events captured with video-encephalogram (video-EEG) over a 6-year period at Shenzhen Children's Hospital. Result: There were 1000 patients under two years of age with suspected epileptic events captured with video-EEG. The seizure types were as follows: generalized seizures (including tonic-clonic seizures (n=11), myoclonic seizures (n=31)), epileptic spasms (n=348, with hypsarrhythmia), focal seizures (n=231, the prominent manifestations were reduced or no movement with staring and other seizure types that included simple automatisms and mild convulsive seizures), status epilepticus (n=7, with duration of 30 minutes or longer), non-epileptic events (n=370, the prominent manifestations were slight shaking or whole body rigidity for about one second, the EEG showed movement artifact or no background changes) and complex seizures (n=9, EEG showed one seizure type transferred into another type in one event). Conclusion: Video-EEG monitoring is helpful in the classification of seizures in infants with epilepsy. Epileptic spasms and focal seizures are main seizure types in infants younger than two years old. They must be differentiated from non-epileptic events as these are also common.
p452 ANALYSIS OF TEMPORAL LOBE EPILEPSY PATHOGENESIS USING DIPOLE SOURCE IMAGING L. E. Betting, P. I. A. M. Silva, A. C. Taborda, and R. G. Fonseca Faculdade de Medicina de Botucatu - UNESP, Botucatu, Brazil
Purpose: Mesial temporal lobe epilepsy (mTLE) associated with hippocampal sclerosis is the most common form of temporal lobe epilepsy. Its mechanism is not restricted to the amygdalo-hippocampal system. The objective of this study was to investigate features of temporal epileptiform discharges using quantitative EEG in three situations: mTLE, mTLE with dual pathology and mild mTLE. Method: Subjects underwent routine EEG which was performed according to previous recommendations. EEGLAB software was used for EEG processing and analysis. All epileptiform discharges were selected and stored. Discharges were submitted to decomposition by independent component analysis. For dipole fitting a spherical four-shell head model and nonlinear adjustment were used. A single equivalent dipole source model was calculated for each component. To identify common patterns of discharge propagation cluster analysis of the equivalent dipole obtained for each component was used. Closely located dipole sources were classified into same subsets (clusters). Result: Refractory mTLE: 9 patients (7 women, mean age 4510). 92 discharges evaluated. Source analysis showed the main independent component clusters (ICC) centroids in the hippocampus, cingulate gyrus, fusiform gyrus and frontal lobe. mTLE with dual pathology: 6 patients (4 women, mean age 5213). 35 discharges evaluated. ICC centroids were in the hippocampus, insula, cingulate gyrus and fusiform gyrus. Mild mTLE: 3 patients (0 women, mean age 3715). 11 discharges evaluated. ICC centroids were in the insula, superior temporal gyrus and cingulate gyrus. Conclusion: We confirmed involvement of extrahippocampal regions in mTLE. Furthermore, patients with different forms of mTLE have distinct networks involved in the pathophysiology of the disease.
p450 ASSESSMENT OF NAMING IN TEMPORAL LOBE EPILEPSY PATIENTS: A COMPARISON OF AUDITORY AND VISUAL CONFRONTATION TESTS M. Elisak, J. Amlerova, P. Marusic, and A. Javurkova 2nd Faculty of Medicine, Charles University in Prague, University Hospital Motol, Prague, Czech Republic
Purpose: The impairment of naming in patients with left temporal lobe epilepsy (TLE) has been well described. Boston Naming Test based on visual confrontation is used as a gold standard; Auditory Naming Test is performed less frequently. The aim of our study was to compare the results of auditory and visual confrontation naming tests in TLE patients. Method: We investigated 20 adult patients with unilateral refractory TLE (mean age 40 years; FSIQ 99 [range 75 to 122]; 10 left- and 10 right-sided). Both naming tests (Czech versions) were performed and obtained scores were categorized as normal or abnormal (failed). The cut off values were calculated from a control group study. Result: Seven (7/10) left-sided and 2/10 right-sided TLE patients failed Boston Naming Test compared to 6/10 left-sided and 4/10 right-sided who failed Auditory Naming Test. Scores from both tests strongly correlated (p =0.001), however on individual basis in three patients the results were contradictory. Conclusion: Strong correlation was found between the results of Boston Naming Test and Auditory Naming Test. However in individual patients assessment of naming can vary according to the test used. Boston Naming Test seems to have better lateralizing value.
p451 SEIZURES CAPTURED WITH VIDEO-ELECTROENCEPHALOGRAM IN INFANTS WITH EPILEPSY J. Liao, L. Song, and Y. Chen Shenzhen Children's Hospital, Shenzhen, China
Purpose: To investigate the seizure types seen in infants.
p453 BLINK REFLEX AT ANTICONVULSIVE THERAPY EFFICACY ESTIMATION V. Semashko*, V. Kistsen, and V. Evstigneev *BelMAPGA, Minsk, Belarus; and Belarussian Medical Academy of Postgraduate Education, Minsk, Belarus
133 Abstracts
Purpose: The aim of our study is to estimate the self-descriptiveness of Blink Reflex (BR) as a predictor of epilepsy behavior character (exacerbation or remission) and treatment efficacy. Method: Thirty patients (mean age 35.42.9 years) with temporal epilepsy were studied. Blink Reflex was evoked by electric supraorbital stimulus. Latency, duration, amplitude of R1, R2 components and R3 presences were evaluated. Result: Hyperexcitable BR type presented in 18 (60%) of patients before anticonvulsive therapy. That BR type characterizes: 1). early R1 appearance; 2). prolongation of R1 and R2 duration; 3). R2 polyphasy and high amplitude; 4). R3 presence. Seven patients (23.5%) had normal BR, others - hypoexcitable. We observed all patients every 4 weeks during 3 months with seizure frequency registration and electroencephalography (EEG) control. High seizure frequency correlates with early R1 appearance (r=0.57, p=0.042), prolongation of R2 duration (r=0.55, p=0.049) and R3 presence (r=0.7, p=0.006). During anticonvulsive therapy most R2 duration reduction was obtained in subgroup of patients whose took depakine with topiramate (r=0.74, p=0.003). BR type and its parameters normalization have not correlations with brain damage localization (neocortical dysplasia or mesial temporal sclerosis) and epileptiform discharge occurrence in EEG. Before seizure reduction R3 component was registered in focus side at 100% cases. Conclusion: Complex Blink Reflex parameters (R1 latency, R2 duration and R3 presence) can be use to estimate prognosis of anticonvulsive therapy efficacy.
p455 SEIZURE PROPAGATION ANALYSIS VIA SEGMENTATION OF ICTAL ELECTROCORTICOGRAPHY S. Pirker*, C. Flamm, A. Graef, M. Deistler, and C. Baumgartner* *General Hospital Hietzing with Neurological Center Rosenhgel and Karl Landstein, Vienna, Austria; and Institute for Mathematical Methods in Economics, Vienna University of Technology, Vienna, Austria
Purpose: Surface electroencephalography (EEG) is often limited by movement artifacts, suppression of high frequencies and low spatial resolution. Therefore non-invasive recordings do not always reveal a precise identification of the seizure onset zone especially in patients with non-lesional epilepsy. Invasive subdural strip electrodes allow for a better identification of the seizure onset zone. A semi-automatic evaluation of ictal activity and propagation may support clinicians performing video EEG monitoring. Method: Invasive subdural strip electrodes were implanted to record electrocorticograms (ECoGs) during video EEG monitoring in a drug-resistant patient with focal epilepsy. The patient suffered from four seizures during invasive recording. A novel software was designed for automatic segmentation of individual ECoG channels on the basis of power changes in selected frequency bands. Each segment was evaluated automatically with regard to the predominant frequency. Segments with a predominant theta frequency were categorized as ictal activity by this program. Result: Three seizures were analyzed using this novel segmentation method. Seizure onset on individual channels as detected with this method was well correlated with the visual analysis of ECoGs. In addition, time spread of theta activity on individual channels allowed an evaluation of seizure propagation. Conclusion: Our ECoG segmentation method may allow for a faster and more objective seizure onset detection and description of ictal activity propagation in ECoG. Knowledge of ictal activity propagation may be useful for a better prediction of seizure outcome after epilepsy surgery.
p454 THE SCN1A-PLOYMORPHISM AND CARBAMAZEPINE - EFFECTS ON CORTICAL EXCITABILITY IN HEALTHY ADULTS IN A TMS-STUDY IN THE EPICURE-CONSORTIUM A. Hermsen*, K. Menzler*, P. S. Reif*, K. Balkenhol*, H. Bugiel*, K. M. Klein*, C. Duddek*, H. M. Hamer, H. Trucks, T. Sander, A. Haag*, and F. Rosenow* *Philipps-University Marburg, Marburg, Germany; University Hospital Erlangen, Erlangen, Germany; and Cologne Center for Genomics (CCG) Cologne University, Cologne, Germany
Purpose: SCN1A encodes a voltage-gated sodium channel and acts in neuronal depolarization. Mutations lead to various epilepsy syndromes. Studies revealed a correlation between genotype of SCN1A-polymorphism (IVS5N+5 G->A; dbSNP: rs3812718) and pharmacoresponse to Carbamazepine (CBZ) Transcranial magnetic stimulation (TMS) measures drug induced cortical excitability changes. Purpose: SNP- effect on cortical excitability as measured by baseline/CBZTMS Method: Genotyping: 272 volunteers, 140 homozygotic (AA: 53.5%, GG: 46.5%). Whole TMS- samples of 92. TMS-parameter: motor evoked potentials in RMT, interstimulus intervals, cortical silent period (CSP). Offline Analysis. Design: double-blind, randomized, cross-over; two visits (TMS at baseline & 5 hours after 400mg CBZ or Placebo p.o.). Result: No age or sex differences. CBZ (medium level: 4.53 mg/ml) resulted in higher excitability threshold (p=0.001). Genotypes did neither differ in baseline cortical excitability (p=0.290) nor in response to CBZ (p=0.154) as measured by RMT. However, CSP was prolonged after CBZ for GG and not AA (p=0.015) Conclusion: We did not find significant baseline differences for the genotypes. Differential reaction to CBZ was apparent only in CSP; GG was associated with a higher increase in CSP duration than AA. CSP reflects the function of GABAergic interneurons, which are disturbed in functional SCN1A disorders. The study shows that pharmacogenetic group differences can be proven by TMS.
Semiology, Aetiology and Classification 11 Tuesday, 02 October 2012

p456 LONG-LASTING EPILEPSY INDUCES PROGRESSIVE CHANGES IN THE BRAIN: EVIDENCE FROM TYPE II FCD PATIENTS A. Finardi*, F. Colciaghi*, C. Marras*, L. Castana, P. Nobili*, M. Bramerio, G. Lorusso, and G. Battaglia* *IRCCS Neurological Institute Carlo Besta, Milano, Italy; and Niguarda General Hospital, Milano, Italy
Purpose: To explore whether severe epilepsy is a dynamic pathologic process able to induce structural changes in the malformed brain of patients affected by type II focal cortical dysplasia (FCD), frequently characterized by severe epilepsy. Method: We analyzed four pediatric and four adult type II FCD patients surgically treated for drug-resistant focal epilepsy. In epileptogenic-dysplastic as well as in adjacent normal-appearing areas we performed careful morphologic and morphometric analysis. We also analyzed the NMDA receptor complex composition using protein fractions specifically enriched in post-synaptic densities. Result: Larger dysmorphic neurons (soma size >1100lm2) were mainly present in the epileptogenic areas from type II FCD patients with a longer
134 Abstracts
epilepsy history (>10years); we found a strong and statistically significant positive correlation between the percentage of these neurons and duration of epilepsy (r=0.9; **p<0.01). In the same epileptogenic areas these data were paralleled by reduced neuronal cell density, statistically significant in deep layers of the cortex (*p<0.05), and by a high degree of reactive gliosis. Finally, in all considered FCD patients we found increased expression of NMDA regulatory subunits in the post-synaptic membranes of dysmorphic neurons; a concomitant increase of NMDA scaffolding protein levels was also present in the post-synaptic fraction of adult patients. Conclusion: Our morphometric data support the hypothesis that cellular abnormalities observed in type II FCD epileptic patients could be worsened by a long history of severe, repeated seizures and indicate that abnormalities of NMDA receptor complex and associated proteins are consistently associated with, and may sustain epileptogenesis of type II FCD patients. per s and AEDs. The aim of the study is to evaluate incidence of SD in epileptic men, type of epilepsy, AEDs, frequency of seizures, seric hormonal profile and depression. Method: 61 patients between 1867 yrs were recruited. 50.8% had idiopatic generalised epilepsy and 49.2% had focal epilepsy (temporal 53.3%). 43.5% had frequent seizures. 78.7% were in monotherapy while 21.3% on polypharmacy. VPA was the most frequently used AED, alone or in association with others. Result: SD had a greater prevalence related to age. There isn't association between types of epilepsy as well as AEDs and SD (only PB was slightly significant). No association was found between types of epilepsy and hormonal changes whereas these were found to be correlated to assumption of CBZ. An association was found between the presence of hormonal changes and SD in epileptics treated with AEDs, but not with orgasmic disfunction. Among all patients 61% showed depressive changes and there is a correlation between depression and SD as well as changes of libido and erectile disfunction but not orgasmic. Conclusion: Our results indicate that there isn't an association between the type of epilepsy and the presence of SD whereas they show an association between SD, hormonal changes and AEDs. Particularly CBZ and PB should be avoided in pts who present some impairment of sexual functions and in olders. Furthermore, the depression in epileptics may influence sexual functions.
p457 REFRACTORY CONVULSIVE STATUS EPILEPTICUS AS THE FIRST MANIFESTATION OF SYSTEMIC LUPUS ERYTHEMATOSUS I. Unterberger, M. Bergmann, M. Prieschl, G. Walser, G. Luef, G. Ratzinger, and N. Sepp Medical University Innsbruck, Innsbruck, Austria
Purpose: Refractory status epilepticus (SE) is an uncommon symptom in systemic lupus erythematosus (SLE) despite the case definition of neuropsychiatric manifestation of SLE. Method: A 54-year-old female patient presented with a sudden onset of refractory convulsive SE. Conventional antiepileptic drugs failed to control seizures and thiopental anesthesia has been needed for over 100 consecutive days. Laboratory tests exhibited anaemia (hb 91g/l) and leucopenia (3.0 G/l), routine test for vasculitis was negative. Cerebrospinal fluid (CSF) examination showed white blood cell 8/ll, red blood cell 33/ll with normal CSF/serum glucose ratio and no oligoclonal bands. Extensive CSF and blood work-up and brain biopsy failed to detect any viral, bacterial or fungal origin. Initial brain MRI showed marked bilateral hippocampal T2 hyperintense signal. Consecutive brain MRIs revealed marked bilateral hippocampal atrophy and a vascular ischemic lesion in the right basal ganglia. Starting from the first day intravenous acyclovir was administered. Clinically, the patient has been suffering from medically refractory ongoing temporal lobe seizures and severe neuropsychological deficits. Several years later the patient exhibited a generalized exanthema multiforme. In addition, she reported bilateral leg weakness with hypaesthesia, resembling severe axonal neuropathy. Laboratory tests showed leucopenia (2.5 G/l), elevation of antinuclear antibodies (ANA) (1:1280), anti-ds DNA (1:160), positive RNP/Sm antibodies and positive antiphospholipid antibodies. Result: SLE was diagnosed and treatment with oral corticosteroids (80mg/d) was started with slow tapering to 16mg/d. The patient improved clinically and laboratory tests showed normalization or marked recovery. Conclusion: SLE should be considered in unexplained SE, even if initial laboratory tests are not definitive
p459 MEDICAL TREATMENT OF FOCAL CORTICAL DYSPLASIA: A CASE SERIES OF 11 PATIENTS S. H. Kim, H. W. Ryu, J. H. Lee, B. C. Lim, J. H. Chae, Y. S. Hwang, and K. J. Kim Seoul National University Children's Hospital, Seoul, Korea
Purpose: Focal cortical dysplasia is often associated with intractable epilepsy. Outcome after surgical treatment has been evaluated in various studies, but the role of medical treatment remains largely unknown. We retrospectively evaluated the clinical features and long-term outcome in 11 patients with focal cortical dysplasia who initially responded well to medical treatment. Method: Patients with focal cortical dysplasia who achieved more than 2-year seizure freedom with antiepileptic drugs (AED) were analyzed. Clinical, seizure and electroencephalographic (EEG) features were collected. Types of AED, time to seizure cessation from commencement of AED and outcome after discontinuation of AED were assessed. Result: Eleven patients (age range, 0.5 - 17.3 years) were included. Median seizure free period was 3.6 years (range, 2.2 - 11.4 years). The median total number of seizure events before treatment was 6 (range, 2 30). Seizure control was achieved immediately after commencement of drugs in 45%, and within 2 months in 91%. Eight (73%) patients obtained seizure control with the first AED. Seizures responded best to oxcarbazepine, which achieved seizure control in 6 patients (55%). Discontinuation was attempted in 5 patients with a successful outcome in 3 patients. EEG studies were normal in 5 (45%) patients before treatment, and normal in 8 (73%) patients after treatment. Conclusion: This study suggests that some patients with focal cortical dysplasia may respond well to medical treatment, especially when immediate seizure control is achieved with the first AED.
p458 SEXUAL DISFUNCTIONS, AEDS AND SERIC HORMONAL PROFILE IN EPILEPTIC MEN L. Zummo, L. Urso, M. Gammino, V. Calabr, D. Urso, and O. Daniele University of Palermo, Palermo, Italy
Purpose: Sexual Disfunctions (SD) are common in epileptics with a prevalence between 3871%. Aetiology is multifactorial, due to epilepsy
p460 GAD65 - GAD67 MRNA AND PV EXPRESSION IN HUMAN FOCAL CORTICAL DYSPLASIA V. Medici, L. Rossini, R. Garbelli, L. Tassi, and R. Spreafico I.R.C.C.S. Foundation Neurological Institute, Milan, Italy
135 Abstracts
Purpose: Epileptic tissue is characterized by an imbalance in the network activity, and several studies reported that inhibitory function is damaged in dysplastic tissue. A consistent decrease in the number of inhibitory interneuronal subsets expressing parvalbumin (PV), in tissue resected from patients with Focal Cortical Dysplasia (FCD) was showed. In order to verify if the decrease of PV protein expression observed in epileptic tissue corresponds to a parallel impairment in GABAergic compartment, we analyzed 48 surgically treated patients operated on for intractable epilepsy including 38 patients with FCD (type I, II and III) and 10 patients without any visible lesion (cryptogenic). Seven control cases were also analyzed. Method: Serial sections were processed using in situ hybridization and immunocytochemical techniques. Slides were immunostained for GAD65 and GAD-67 probes and for antibody against PV. The density of inhibitory PV-immunoreactive interneurons in relation to GABAergic cells was estimated in controls and in all different pathological groups by using a two-dimensional cell counting technique. Result: The density of PV-immunoreactive interneurons was reduced in pathological groups as compared to the controls. However mRNA levels of GAD-67 and GAD-65 were similar both in control and in FCD cases. Although the PV reduction was observed thought all the cortical thickness, layers III and IV, where the protein normally is more expressed, were observed to be particularly affected. Conclusion: Preliminary results show that in FCD patients PV reduction is not apparently correlated with the mRNA reduction of GAD-65 and GAD-67.
p462 M. PNEUMONIAE IN CEREBROSPINAL FLUIDS OF CHILDREN WITH NEUROLOGICAL MANIFESTATIONS: A CASE/CONTROL STUDY; TEHRAN, IRAN S. Noorbakhsh, V. Zarabi, F. Khodapanahandeh, and A. Tabatabaei Tehran University of Medical Sciences, Iran, Tehran, Iran
Purpose: Searching the M. pneumoniae DNA and antibody (IgG) in CSF of children with neurologic manifestations. Method: This case control study done in pediatric wards of Rasoul hospital in Tehran (20082010). The M. pneumonia DNA and IgG (ELISA) level in CSF samples compared between 55 cases with neurological manifestations [mean age: 3.84 3.43 years ]; and 10 controls (simple febrile seizure with normal CSF). Chi square values<0.05 were considered statistically significant. Sensitivity; specificity; PPV; NPV for CSF antibody level determined by using the Area under the Roc Curve. Result: Positive M. pneumoniae - DNA detected in the CSF of 1 with GBS (1/53; 2%); Cut off level for antibody was 0.0025, AUC was 0.876 (%95 CI, 0.78 0.96; P Value =0.000); 73% sensitivity; 90% specificity; 100% PPV; 28.8% NPV. CSF antibody had significant difference between cases and controls [0.080.26 vs 0.0010.001; P value: 0.02, Kappa =0.27). Lowest IgG level reported in cases with aseptic meningitis (without encephalitis); the highest IgG level observed in cases with focal neurologic signs. Conclusion: Detecting the M. pneumonia-DNA in CSF was rare (2%). IgG level in CSF even in very low amount had 70% sensitivity; 90% specificity and 100% PPV especially in cases with encephalitis, GBS or other focal neurologic signs but not in cases with aseptic meningitis. CSF-IgG test (NPV=28.8%) was weak for ruling out the M. pneumoniae as the etiologic cause in cases with neurologic manifestations. The positive PCR-DNA in the CSF is more reliable for diagnosing the recent M. pneumonia infection.
p461 THE CLINICAL SPECTRUM OF HEMIMEGALENCEPHALY IN CHILDREN F. X. Sanmarti*, M. I. Sigatullina, J. Campistol*, and S. S. Shamansurov *Hospital San Joan De Deu, Barcelona, Spain; and Tashkent Institute of Postgraduate Medical Education, Tashkent, Uzbekistan
Purpose: To analyze the clinical features of different types of Hemimegalencephaly Method: MRI and continuous Video-EEG investigation were performed in 7 patients with Hemimegalencephaly. Evolutionary postoperative follow- up of 2 patients with transferred Hemispherectomy was reviewed Result: 3 patients have an isolated type of Hemimegalencephaly and 4 patients a syndromic type, which were associated with ipsilateral hemihypertrophy of the whole body. Six patients had seizures (severe refractory epilepsy- 5, febrile seizures-1). The mean age of the epilepsy onset was 3, 7 (0, 113) months. All patients had a contralateral hemiparesis, generalized hypotonia and developmental delay that went from severe to the mild degree. The seizure semiology was ranged from febrile seizures to the polymorphic types, like myoclonic seizures (2), complex partial seizures (3), asymmetric tonic spasms (1) and focal clonic sezures (1). In all cases a continuous theta and delta activity in the involved hemisphere was registered. In 3 cases registered continuous burst-suppression pattern in the side of Hemimegalencephalia. In 2 patients with severe progressive epileptic encephalopathy a functional hemispherectomy was performed with the result as 90% of seizure reduction in 2 patients. Postoperative hemiparesis in patients was not more severe than that before surgery. Cognitive outcome was much better after operation in both patients Conclusion: In most cases, a clear correlation was found between the side of the Hemimegalencephaly and seizure semiology which were also confirmed by the continuous Video-EEG register. Early intervention is important to prevent encephalopathy and compromise of function within the unaffected hemisphere.
p463 DATA-DRIVEN PHENOMIC ANALYSIS OF EPILEPTIC ENCEPHALOPATHY PHENOTYPES USING AN ONTOLOGY-BASED PHENOTYPE DATABASE J. A. Albers*, S. Weckhuysen, A. Suls, B. Coessens, P. N. Robinson, P. De Jonghe, C. R. P. Euroepinomics Res**, and I. Helbig* *University Medical Center Schleswig Holstein, Kiel, Germany; University of Antwerp, Antwerp, Belgium; Cartagenia N.V., Leuven, Belgium; Charit - Universittsmedizin Berlin, Berlin, Germany; Neurogenetics Group, ANTWERP, Belgium; and **Strassbourg, France
Purpose: Epileptic encephalopathies constitute a phenotypically challenging group of seizure disorders. We aimed to apply novel phenomic strategies for the characterization of epilepsy phenotypes by combining an ontology-based phenotype database with data-driven identification of novel phenotypic associations. Method: We constructed a validated epilepsy ontology, which was implemented in the Human Phenotype Ontology (HPO) and used as the data entry matrix the web-based Cartagenia BENCH phenotype platform of the EuroEPINOMICS-RES consortium. The phenotypic data of 86 patients with West syndrome, Dravet syndrome, and myoclonic astatic epilepsy were then systematically analyzed for phenotypic similarities, assessing the frequency of combinations of various unique phenotypic traits. Combinations were screened by two expert reviewers for novel or unexpected combinations of epilepsy phenotype traits.
136 Abstracts
Result: Phenotypic data analysis revealed 1431 different combinations of phenotypic traits. 338 of these combinations were annotated at least in two patients. While most combinations of phenotypic traits were common combinations in the three inserted epilepsy syndromes, we found three rare combinations present in at least three patients from different centers, which were followed up by refined phenotyping to explore possible subgroups. Conclusion: Analysis of large-scale phenomic data permits subgrouping of patients with similar epilepsy phenotypes. This clustering may provide the basis for data-driven delineation of novel epilepsy phenotypes in rare epileptic encephalopathies. Method: 42 patients (1760 aged) with AVMs manifesting with epileptic syndrome (frequent severe partial seizures with secondary generalization) were included in the analysis. All the patients received active endovascular superselective embolizations of AVMs using HepasSphere microspheres (BioSphere Medical, France) loaded with anticonvulsant (Diazepam). The treatment involved neurophysiologic control of dynamic EEG monitoring in all stages. Result: 58 surgeries in 42 patients were performed on the same technique. Total and subtotal AVM embolization was achieved in 29 patients and partial in 13. Electroclinical observations with catamnesis to 3 years showed a positive postoperative adaptive dynamics of the epileptic syndrome with a distinct tendency toward inhibition of epileptic manifestations. All the patients had a significant decrease in the frequency and severity of epileptic seizures, in a number of observations changes in the structure of seizures, 27 (64%) patients had the attacks completely stopped (Engel class I). EEG proved full regression of paroxysmal activity with a tendency toward normalization of the spatial bioelectrical pattern. Conclusion: The proposed modernized method of active surgical treatment of symptomatic epilepsy in patients with cerebral AVM (HepaSphere with anticonvulsant) provides a significant increase in the effectiveness of treatment through direct targeted delivery of anticonvulsant immediately into the brain and a creation of its prolonged depot in the nidus of AVM under the control of EEG monitoring.
p464 A DECADE OF EXPERIENCE WITH DEEP BRAIN STIMULATION FOR PATIENTS WITH REFRACTORY MEDIAL TEMPORAL LOBE EPILEPSY M. Sprengers, K. Vonck, E. Carette, A. Meurs, D. Van Roost, and P. A. J. M. Boon Ghent University Hospital, Ghent, Belgium
Purpose: To evaluate the long-term results of mesial temporal lobe (MTL) deep brain stimulation (DBS) as an alternative therapy for patients with MTL epilepsy. Method: Since 2001, 11 patients with refractory MTL epilepsy underwent MTL DBS. When unilateral MTL DBS failed to decrease seizures with >90% after 3 years, a switch to bilateral MTL DBS was proposed. Result: After a mean follow-up of 8.5 years, 6/11 patients have a 90% seizure frequency reduction with 3/6 seizure free for > 3 years; three patients have a 4070% and 2 have a <30% reduction. Best outcome was found in patients with a focal unilateral ictal onset. None of the patients reported permanent symptomatic side effects. Regarding the chronic stimulation protocol, four relevant assessments were made. 1) Augmenting output voltage mostly did not affect seizure frequency, but in three cases it did. 2) Starting bilateral DBS resulted in improved seizure control in 3/5 patients. 3) Introducing day-night cycling (DBS off between 0 and 6 am) after a stable frequency reduction had been reached did not affect seizure frequency in 4/5 patients. 4) Switching DBS off during at least a month in 7 patients was associated with an immediate or delayed increased seizure frequency in 4/7 patients, did not affect seizure frequency in 2/7 patients and coincided with seizure freedom in 1/7 patient. Conclusion: This open study with an extended long-term follow-up demonstrates maintained efficacy of DBS in MTL structures for patients with refractory medial temporal lobe epilepsy. Bilateral MTL DBS may herald superior efficacy in unilateral MTL epilepsy.
p449 HIGH-RESOLUTION EEG ELECTRICAL SOURCE IMAGING CONTRIBUTES TO LOCALIZE THE EPILEPTOGENIC ZONE IN MALFORMATIONS OF CORTICAL DEVELOPMENT E. Rikir*, L. Koessler, M. Gavaret, J. Jonas, S. ColnatCoulbois, J. Vignal, H. Vespignani, and L. Maillard *CHU Sart-Tilman, LIEGE, Belgium; CRAN, Nancy, France; CHU de la Timone, Marseille, France; Centre Hospitalier et Universitaire, Nancy, France; and CHU de Nancy, Nancy, France
Purpose: Malformations of Cortical Development (MCD) are increasingly recognized using MRI and EEG. However, localizing the epileptogenic zone (EZ) associated with MCD still relies on intra-cranial EEG recordings. Our purpose was to study the spatial correlations between the modeled electrical sources of inter-ictal events (Interictal Zone = IZ) recorded with High-Resolution scalp EEG (HR-EEG) and the EZ defined by stereo-EEG (SEEG) in MCD. Method: This prospective, bi-centric study enrolled 21 consecutive patients (19 in Nancy and 2 in Marseille) with MCD undergoing pre-surgical investigations between 2008 and 2011 and comprising a HR-EEG (64-channels) with electrical source imaging and SEEG recordings. Result: Three patients were excluded from the analysis because of missing data. HR-EEG IZ co-localized with the EZ in three cases (2/3 were MRI negative). HR-EEG IZ and SEEG EZ were completely or more often partially overlapping in 94%. In six cases, the HR-EEG IZ comprised the entire EZ and extended to the propagation zone in 4/6. In 4 patients with temporal lobe epilepsy, HR-EEG IZ was completely included into the EZ. In these cases, the HR-EEG IZ missed the medial temporal component of the EZ. In 4 cases, HR-EEG IZ partially overlapped the EZ. In 7 patients with negative MRI, HR-EEG correctly localized at least a part of the EZ. In 2/7, it allowed its precise localization. Conclusion: HR-EEG combined with electrical source imaging helps to localize and target the EZ associated with established or suspected MCD particularly in MRI negative cases.

p465 INNOVATED SURGICAL TREATMENT OF EPILEPTIC SYNDROME IN PATIENTS WITH BRAIN ARTERIOVENOUS MALFORMATIONS V. Panuntsev, L. Rozhchenko, T. Stepanova, V. Aliev, and R. Gafurov Russian Polenov Neurosurgical Institute, Saint-Petersburg, Russian Federation
Purpose: To investigate the results of treatment of epileptic syndrome (symptomatic epilepsy) in patients with cerebral arteriovenous malformations (AVM) based on the modernized method of intravascular surgery under EEG control.
137 Abstracts
p449 SENSITIVITY OF A 256 CHANNEL EEG RECORDING IN TEMPORAL MESIAL SCLEROSIS PATIENTS AND TEMPORAL NEOCORTICAL PATIENTS C. Arcaro, A. Del Felice, E. Formaggio, S. Storti, I. Boscolo Galazzo, R. Mai, A. Fiaschi, and P. Manganotti Universit degli Studi di Verona, Verona, Italy
Purpose: to describe the augmented sensitivity of a 256 channel EEG recording in the epileptiform activity scalp localization by visual inspection of patients affected by temporal mesial sclerosis and neocortical temporal epilepsy. Exploiting 20 left and 20 right electrodes covering face between orbitary floor and the upper margin jaw (anterior and posterior zygomatic electrodes) we underlie the accuracy and non-invasivity of this method. Method: we recorded a rest 256 channel EEG in 14 patients (7 female and 7 male mean age 42 years) affected by temporal epilepsy. We considered six mesial temporal sclerosis patients and three neocortical temporal patients. We then compared the scalp localization of epileptiform abnormalities by visual inspection through the standard 1020 bipolar and monopolar montages and later through the 256 Topo Plot Average Reference Map e.g. a projection of each electrode's activity on a scalp model. Result: in temporal mesial sclerosis patients, EEG abnormalities observed in fronto temporal standard 1020 montage are seen with the highest negative peak in anterior zygomatic channels (Topo Plot Map montage), while temporal neocortical patients underling a large field potential are seen in posterior zygomatic electrodes. Conclusion: since the basal temporal cortex is tangential to the lateral surface of the skull and neocortical epilepsy underlies a large field potential, anterior and posterior zygomatic electrodes respectively could be considered at the same time as a non-invasive method and specific tool to increase the maximum peak localization by visual inspection in patients affected by temporal mesial sclerosis and temporal neocortical epilepsy patients. Conclusion: Sexual dysfunction and alterations in sex hormones may occur frequently in epilepsy patients. The most significant finding of our study was high rates of sexual dysfunction in women. Further studies are necessary to support our findings.
p469 EPILEPSY AND REPRODUCTIVE DISORDERS I. A. Zhidkova, and T. V. Kaznacheeva Moscow State Medical Dental University, Moscow, Russian Federation
Purpose: To determine reproductive endocrine disorders among women with epilepsy (WWE), who were long-term treated with antiepileptic drugs (AED). Method: Group I included 107 women with epilepsy of reproductive age (mean age 25.6 6.2 years). A comparison group II consisted of 47 women with polycystic ovary syndrome (PCOS) (mean age 26, 7 5.7years). All women were investigated: sex hormones luteinizing hormone (LG), follicle-stimulating hormone (FSH), prolactin (PRL), estradiol (E), progesteron (P), testosterone (T); dynamic ultrasound examinations; evaluation clinical symptoms of hyperandrogenism. The comparative study based on diagnostic criteria of PCOS, taken in 2003 (The Rotterdam ESHRE/ FSRM-Sponsored PCOS consensus of workshop group, 2003). Result: 73% women with epilepsy were healthy. 27% of WWE from group I had ovary dysfunction; menstrual disorders revealed among women using valproate (VPA, doses > 1200 mg/day) more often than among WWE using new AED (lamotrigine (LTG), topiramate, levetiracetam (LEV), oxcarbazepine). 7.2% WWE had hirsutism; 1527% functional hyperprolactinemia; 21% -increased testosterone; 20% - hipoprogesteronemia. Results of ultrasound examinations showed that ovary volume in WWE was normal and significantly less than in group II with PCOS (p0.05). Conclusion: The comparative study in these groups revealed that there were no signs characteristic of diagnosis of PCOS in women with epilepsy compared to the women with PCSO. Menstrual cycle disturbances were reversible: replacement of VPA with LTG or LEV normalized endocrine function in women with a previous endocrine disorders.
p449 THE EVALUATION OF SEXUAL FUNCTIONS AND SEX HORMONES IN MALE AND FEMALE EPILEPSY PATIENTS WHO ARE ON VALPROIC ACID AND CARBAMAZEPINE MONOTHERAPY A. Erdal, G. Kutlu, Y. Bier Gmceli, and L. E. Inan Ministry of Health, Ankara Research and Training Hospital, Ankara, Turkey
Purpose: In patients with epilepsy, sexual dysfunction is seen at an higher incidence than in patients with other chronic neurologic diseases. In this study, we examined sex hormone levels and sexual dysfunction in patients with epilepsy who used carbamazepine (CBZ) and valproic acid (VA) monotheraphy. Method: There were overall 35 patients in the study; 18 patients who used VA and 17 patients who used CBZ. These patients medical history, epilepsy history, sex hormone levels, drug blood levels, Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A) and Arizona Sexual Experience Scale (ASES) levels were examined. Result: The rate of sexual dysfunction was found to be higher in women patients with epilepsy than men irrespective of drugs, anxiety and depression. Dehydroepiandrostenedionesulphate (DHEAS) and progesterone (PG) levels were found to be higher in male patients who used VA. Free testesterone (FT) levels were important both for male and female sexuality. The number of pregnancies was lower in female patients using VA and we think that it was associated with VA induced hyperandrogenism.
p470 TISSUE DOPPLER EVALUATION OF DIASTOLIC FUNCTIONS IN PATIENTS WITH NEWLY DIAGNOSED AND UNTREATED PATIENTS WITH GENERALIZED EPILEPSY M. Bilgi, D. Yerdelen, and Y. Colkesen Baskent University Faculty of Medicine, Adana, Turkey
Purpose: Background: Sudden unexpected deaths in patients with epilepsy (SUDEP) are common. Epileptic discharges alter vital autonomic control of cardiac functions by affecting central autonomic network. Ratio of early mitral flow velocity (E) to early mitral annulus velocity (e) (E/e) is a reliable noninvasive parameter that reflects increased left ventricular diastolic pressure. This measure is correlated with the severity of diastolic dysfunction. Aim: The purpose of the present study is to determine the diastolic functions of left ventricule by assessing E/e ratio in patients with generalized epilepsy. Method: Thirty consecutive patients with generalized epilepsy and age and gender matched control group prospectively enrolled. Mean age of the epilepsy group was 279 and 53% were male. The diagnosis of epilepsy was newly established in all patients, and they had not previously used any antiepileptic drugs. The duration and frequency of seizure were 2 days to 30 years and everyday to twice in 30 years, respectively. Diseases and treatments that may affect cardiac and autonomic functions were exclusion criteria. The subjects were evaluated by tissue Doppler echocardiography and E/e ratio were calculated.
138 Abstracts
Result: E/mean e ratio was 8.22 2.52 in patients with generalized epilepsy and 6.74 1.10 in control group (p = 0.005). Conclusion: The significant elevated E/mean e value in patients with generalized epilepsy compared with control group demonstrates that left ventricular diastolic pressure is affected unfavorably and left ventricular filling pressure is elevated indirectly in epilepsy group. This finding may be as a result of autonomic cardiac dysfunction encountered in patients with epilepsy. Our results suggest that tissue Doppler echocardiography may be used to anticipate autonomic cardiac dysfunction and SUDEP in future. with epilepsy, aged 45 years, seen at the University Hospital Innsbruck, during a one year period. Additionally we investigate laboratory changes of estradiol and progesterone. Result: Seventy two women had a mean age at last menses of 49.2 years (SD 4.1, range 38 to 57 years). No confounding influences such as history of cigarette smoking, number of pregnancies, or use of enzymeinducing antiepileptic drugs were present. Sixty eight percent of the women reported either that their epilepsy changed or first began during menopause. 53% noted an improvement 1 year after last menses 20%, reported worsening of their seizures with menopause, and 27% described no changes. An elevation of the estrogen to progesterone ratio could be demonstrated in the Perimenopause. Conclusion: Marked hormonal changes in the menopausal transition seem to have an effect on seizure susceptibility.
p471 BURNS: A LESION UNDERESTIMATED IN INTRACTABLE TEMPORAL LOBE EPILEPSY E. Quintero Lpez*, M. P. Mata Mendoza*, M. A. Alonso Vanegas*, H. Sentes Madrid, R. M. Buentello Garca*, and F. Rubio Donnadieu* *Instituto Nacional de Neurologa y Neurociruga, Distrito Federal, Mexico; and Instituto Nacional de Nutricin y Ciencias Mdicas Salvador Zubirn, Distrito Federal, Mexico
Purpose: To investigate and describe the incidence, severity and circumstances of burns during seizures in females with medical intractable temporal lobe epilepsy (TLE). Method: We retrospectively review a series of 100 female patients with intractable pharmacoresistant TLE secondary to mesial temporal sclerosis (MTS) operated at the National Institute of Neurology and Neurosurgery from July 2008 to December 2011. We analyze genre, type and frequency of seizures, socioeconomic status, and nature, severity and circumstances of any burns suffered secondary to seizures. Result: Complex partial seizures (CPS) were present in all patients; mean seizure frequency was 12 (630) per month. Thirty-seven (37%) patients showed and recalled having had burns during a seizure and all these cases belonged to very low socioeconomic status. Main type of burns: scalds from hot fluids, burns during cooking or ironing. Areas of the body most commonly affected were the face, anterior neck, hands and trunk, with major burns in 30%, moderate burns in 40% and minor burns in rest 30%. Conclusion: People with intractable epilepsy have a higher risk of accidental burns than those without seizures. It seems that these lesions are underestimated and a specific question regarding this topic should be approach directly. Socioeconomic status and activity appears to be extremely relevant factors for this condition.
p473 A DECISION SUPPORT MODEL OF PRECONCEPTION COUNSELLING FOR WOMEN WITH EPILEPSY J. Winterbottom*, A. Jacoby, and G. Baker *The Walton Centre NHS Foundation Trust, Liverpool, UK; and The University of Liverpool, Liverpool, UK
Purpose: Women with epilepsy (WWE) are at increased risks of adverse pregnancy outcomes, yet little research has addressed their perceptions of pregnancy-related risks or how they make reproductive health decisions when preparing for pregnancy. Preconception counselling offers an opportunity to prevent and/or reduce risks through health promotion interventions. We undertook a qualitative study to explore professional and patient factors influencing the outcomes of preconception counselling interventions. Method: 85 WWE (mean age 27.8 years) participated in this study, of whom; 61 women took part in a focus group, and 24 women were observed during preconception clinic attendance and later interviewed about decisional outcomes. We explored how women perceived risk information and made judgements concerning pregnancy planning. Result: Four major themes were identified, with some variation between the stages of pregnancy contemplation: (1) differences between lay and professional definitions of planned pregnancy influence decisions to commence preconception interventions; (2) risks are perceived as frightening and fearful focusing on the health of the unborn child; (3) not all women perceive the risks and benefits of preconception interventions in the same way, and (4) women felt uneasy making decisions seen as complex and challenging, and spread over time. Conclusion: The results highlight the individual variability between women's reproductive decisions, influenced by the social contexts of their plans for pregnancy. The importance of recognising personal beliefs regarding pregnancy and seizure-related risks are essential to understanding poor treatment adherence during pregnancy. These findings have important implications for service development and promoting the uptake of preconception care for WWE.
p472 WOMEN WITH EPILEPSY IN PERIMENOPAUSE AND MENOPAUSE G. Luef, A. Kullick, M. Prieschl, M. Bergmann, G. Walser, I. Unterberger, C. Brezinka, and L. Wild Medical University Innsbruck, Innsbruck, Austria
Purpose: The age at which women experience menopause may be influenced by epilepsy. Perimenopause is associated with a decline in serum estradiol and progesterone levels, the perimenopausal development of anovulation is associated with an increase in estradiol to progesterone ratios that can increase neuronal excitability and exacerbate seizures. The aim of our study is to identify if menopause, 1 year after last menses, benefit seizures and would a decrease occur only in women who had a catamenial pattern of seizure exacerbation previously? Method: A standardized questionnaire was applied to evaluate changes of seizures associated to menstrual cycles in 100 consecutive women

p474 LONG TERM PROGNOSIS OF CHILDREN WITH EPILEPSY IN RURAL INDIA D. K. Pal*, S. Sengupta, G. Chaudhury, and T. Das *King's College London, London, UK; and SANCHAR-AROD, Kolkata, India
139 Abstracts
Purpose: The long-term medical and social prognosis of children with epilepsy in developing countries is almost entirely unknown. We conducted a ten year follow-up of 94 children recruited to a randomized controlled trial of antiepileptic drugs (AEDs) in 1996 in 40 villages of rural India. Method: Community disability workers returned to the participants houses and tracked down participants and relatives. To collect follow-up data we used a standardized health questionnaire for medical outcomes, the Social Integration Scale (SIS) for social outcomes, and verbal autopsy methods for deceased individuals. We also administered the SIS to 122 age/sex matched peers for comparison. Result: We traced vital information on 77 of the original cohort (82%). Seven of the 77 were reported deceased with causes including drowning (n=3), accidental (n=1) and unknown (n=3). 40 surviving participants (57%) reported at least one year seizure remission, 17 (24%) had never been seizure-free. Only 11 individuals remained on AEDs. Men with history of childhood epilepsy had significantly less social activity but similar educational and economic opportunities as peers. Women with history of childhood epilepsy were less likely to finish school or take part in social activities, but had the same frequency of marriage and children as peers. Conclusion: Childhood onset epilepsy is associated with a significant mortality in rural India. Survivors have similar rates of long-term seizure remission as in developed economies. Social relations and inclusion are important targets for community-based intervention because these deficits persist from childhood. However, longer term family (for women) and economic (for men) outcomes are favourable. [11C]flumazenil increases (zmax=4.8, 6.2cm3), but not SF patients (zmax=3.8, 0.87cm3). For FDG, NSF showed zmax=4.6, 5.4cm3 and SF zmax=4.1, 0.78cm3. For individuals, periventricular increases versus controls with zmin=3.5 and pmax=0.5 differentiated best between NSF and SF patients, showing increases in 5/7 NSF patients for both [11C]flumazenil and FDG and 1/9 ([11C]flumazenil) and 5/9 (FDG) SF patients (accuracy 81% for [11C]flumazenil, 56% for FDG). Conclusion: If large numbers of control datasets are available, periventricular [11C]flumazenil but not FDG uptake may predict individual postoperative outcome in HS.
p476 MORTALITY RISK IN PEOPLE WITH CONVULSIVE EPILEPSY: 8 YEARS FOLLOW-UP OF A COHORT IN RURAL CHINA D. Ding*, W. Wang, J. Wu, Z. Hong, P. Kwan, G. Bell, H. De Boer**, and J. W. Sander *Fudan University, Huashan Hospital, Shanghai, China; Beijing Neurosurgery Institute, Beijing, China; Institution of Neurology, Shanghai, China; Chinese University of Hong Kong, Hong Kong, China; UCL Institute of Neurology, London, UK; and **SEIN, Halarm
Purpose: Data on mortality, especially providing standardized mortality ratios (SMRs) or describing the cause of death, are still lacking from resource-poor settings. In 2008, we conducted a second follow-up survey in a cohort of people with convulsive epilepsy in eight rural counties in China. This longitudinal prospective study allowed us to investigate the pattern of cause of death and long-term mortality risk among people with epilepsy over eight years of follow-up. Method: We tried to trace all subjects who participated in an assessment of epilepsy management at primary health level during 2000 to 2004. Demographic data, clinical characteristics, survival status and putative cause of death were recorded. The proportional mortality rates (PMRs) for each cause, and SMRs for each age-group and cause were estimated based on the 2004 Chinese population. Multivariate analysis of Cox proportional hazards regression model was used to detect risk factors associated with increasing mortality. Result: There were 203 reported deaths among 1983 people with epilepsy during a mean follow-up time of 6.1 years. The highest PMRs were for epilepsy-related death (41.9%) including drowning (14.3%) and status epilepticus (13.3%). The risk of premature death was 2.9 times greater in people with epilepsy than in the general population. Much higher risk (SMR: 30.0 to 31.3) was found in young people aged 1029 years old. Onset before 12 years old, duration of over 10 years, and living in a waterside area were determined as independent predictors for the increasing mortality due to epilepsy-related death. Conclusion: Epilepsy-related death was the leading putative cause of death in rural China. Predictors of increasing mortality suggest interventions with efficient treatment and education to prevent premature mortality among people with epilepsy in resource-poor settings.
p475 TOWARDS PREDICTING INDIVIDUAL OUTCOME IN PATIENTS AFTER TEMPORAL LOBE SURGERY FOR HIPPOCAMPAL SCLEROSIS: WHITE MATTER FDG AND [11C]FLUMAZENIL BINDING J. Yankam Njiwa*, S. Bouvard, N. Costes, H. Catenoix, P. Ryvlin, and A. Hammers* *Neurodis Foundation, Lyon, France; CERMEP-Imagerie du vivant, Lyon, France; Hpital Neurologique Pierre Wertheimer, Lyon, France; and Institute for Child and Adolescent with Epilepsy (IDEE), Hospices Civils de Lyon, Lyon, France
Purpose: One third of patients with hippocampal sclerosis (HS) undergoing epilepsy surgery fail to become seizure free (NSF); risk factors include bilateral pathology and frequent generalized seizures. At the group level, increased periventricular [11C]flumazenil binding (indicating heterotopic neuron concentration) was associated with NSF outcome (Hammers et al. Epilepsia 2005;46:944948). Here, we investigate in new larger cohorts whether preoperative white matter (WM) uptake of [11C]flumazenil or the more widely used FDG predicts NSF outcome in individuals. Method: Sixteen patients with MRI-defined HS had preoperative FDG and [11C]flumazenil PET, and at least 23 (median 68) months follow-up. They were compared with controls (30 FDG, 41 [11C]flumazenil) using SPM8 with explicit periventricular WM masking. Global radioactivity concentrations were adjusted via group-specific ANCOVA. Different cutoffs for distinguishing NSF and seizure free (SF) patients were investigated. Result: Seven patients were NSF (not Engel IA) during follow-up. NSF versus SF patients had periventricular increases predominating contralaterally on [11C]flumazenil PET (z=2.54.4), which were less marked on FDG PET (z=2.8). Against controls, NSF patients showed prominent
p477 PRIMARY READING EPILEPSY: CASE REPORT H. L. Gul*, O. Karadas, H. Tutkan, and Z. E. Ozturk *Kartal Education and Research Hospital, Istanbul, Turkey; Erzincan Military Hospital, Erzincan, Turkey; Occupational Diseases Hospital, Istanbul, Turkey; and Anatolian Hospital, Kastamonu, Turkey
140 Abstracts
Purpose: Reading epilepsy is a rare form of reflex epilepsy which was first described in 1956 by Bickford et al. Primary reading epilepsy patients have: absence of pathological signs, seizures only following prolonged reading, prodromal sensation of the jaw and generally normal resting EEG. We reported a case of primary reading epilepsy patient that gave response to valproic acid therapy. Method: A 21 year old male presented partial seizures that always occurred during both silent and loud reading. Seizures began at the age of 19 years. Since then; he had experienced a total of 7 seizures in which 2 had become generalized tonic-clonic. He had no family history of epilepsy. Physical and neurological examinations, cranial magnetic resonance imaging were normal. Detailed EEG and activation studies (sleep deprivation, silent and loud reading while EEG) were all normal. Result: Valproic acid treatment 1000mg/day was started. During 6 months of follow up after therapy, he was seizure free. Conclusion: In some patients with primary reading epilepsy, it was not preferred to use drug treatment, especially if they have no generalized convulsions. Reading epilepsy has been reported to respond well to valproate as in our patient. Some patients may worsen with carbamazepine but clobazam or clonazepam may also be needed. Purpose: Assessment the values of the initial clinical predictors of effectiveness of the first antiepileptic drug in the elderly patients with epilepsy. Method: Prospective longitudinal study included consecutive series of elderly with newly diagnosed partial epilepsy. Inclusion criteria were: 1) Subjects older than 65 years, with untreated, newly diagnosed epilepsy 2) Subjects had no previous use of an AED, 3) Electroencephalogram (EEG) compatible with localization-related epilepsy (to exclude primary generalized epilepsy), 4) Neuroimaging confirming the absence of a progressive neurological lesion. Patients were following minimum 12 mounts after initiation of therapy. Primary endpoint was seizure control (with or without seizures). Potential predictors are analyses from dataset available on initial clinical evaluation and included demographic data, history risk factors, neurology findings, neuroradiology and EEG findings as well as characteristics of pharmacotherapy. Univariate logistic regression equations were computed for each potential predictor variable. Variables were included in the multivariate analysis if the univariate p value was < 0.25. A backward selection procedure was then used to select subset variables. Statistical significance was defined for alpha = 0.05. Result: 45 elderly patients were included in this study. 25 remain seizure free after 12 mounts of follow up. Regression analyses demonstrated that etiology particularly depression traumatic brain injury and depression are the most important predictor variables for bad therapeutically response. Conclusion: This study may support hypothesis that neurobiological processes that underpin psychiatric comorbidity may interact with those producing seizures to increase the extent of brain dysfunction and thereby the likelihood of developing bad therapeutic response in elderly.
p478 SILENT STROKES IS A RISK FOR EPILEPSY IN ELDERLY POPULATION I. K. Abdulzahra Hawler Teaching Hospital, 53, Iraq
Purpose: To show the significance of silent strokes as possible risk factor for epilepsy among middle age and elderly patients having late onset epilepsy. Method: This cross-sectional study (survey) was carried out at Rizgary Teaching Hospital, Erbil, Iraq from January to May, 2010. Patients were included in this study if they were middle aged and elderly patients, having unprovoked acquired first seizure or multiple seizures, previously or recently diagnosed as epileptic regardless the number of fits which could be single or multiple, having history of recent or old stroke or TIA. 100 Iraqi patients were included in this survey. The MRI images were examined and interpreted through collaborative discussions between a consultant Radiologist and a consultant Neurologist. Data were tabulated and analyzed, the significance of certain parameters was measured using chi square test, A p-value of 0.05 was considered statistically significant. Result: In this studyepilepsy was mostly observed in elderly population (7079years) and p value was not significant regarding sex differences in the studied sample. Silent strokes were observed mostly in elderly population (6367%). Hypertension, hyperlipidemia, smoking, and old strokes are the commonest comorbidities observed in relation to epileptic patients with silent strokes, and partial secondary generalized epilepsy type was the commonest epilepsy variety observed (73%). Conclusion: Silent strokes were common in elderly patients having epilepsy (53%), and its prevalence increase with age and hypertension. Silent strokes observed in brain MRI can be an indirect way to establish the causes of epilepsy in elderly population.
p480 COMPARISON OF SEIZURE DISTRIBUTION AND EEG RECORDINGS OF EPILEPSY PATIENTS I. Ipekdal*, O. Karadas, H. L. Gul, Z. Gokcil, and Z. Odabasi *Marasal Cakmak Hospital, Erzurum, Turkey; Erzincan Military Hospital, Erzincan, Turkey; Kartal Education and Research Hospital, Istanbul, Turkey; and Gulhane Military Medical Academy, Ankara, Turkey
Purpose: Epileptic seizures may occur during the daytime, at night or both in the daytime and at night. The aim of our study is to investigate the relationship between the distribution of seizures in the day with interictal EEG properties. Method: 48 patients that had generalised or secondary generalised seizures were included to the study. 36 patients had seizures that occur during daytime and 12 patients had seizures that occur during night. Patients interictal EEG properties and distribution of seizures in the daytime were evaluated retrospectively. Result: In interictal EEG recordings of 36 patients that had seizures which occur during daytime: 3 of them showed no abnormalities, 12 showed focal, 21 showed generalised abnormalities. No correlation was detected between these EEG findings and seizure distribution in the daytime. On the other hand, in interictal EEG recordings of 12 patients that had seizures which occur at night: 8 of them showed no abnormalities,3 showed focal, 1 showed generalised abnormalities. Conclusion: These findings suggest that; seizures occuring in the daytime and at night while sleeping may have different mechanisms. Studies that searches for epilepsy-melatonin relationship (like sleep-melatonin relationship) must be made to better understand the etiopathogenesis of nocturnal seizures.
p479 PRIDICTION OF EFFECTIVENESS OF THE FIRST ANTIEPILEPTIC DRUG IN THE ELDERLY PATIENTS WITH EPILEPSY S. Lukic, and M. Spasic University Clinical Centre, Nis, Serbia
141 Abstracts
p481 COEXISTING SEIZURES IN PATIENTS WITH INFANTILE SPASMS CONFIRMED BY LONG-TERM VIDEOELECTROENCEPHALOGRAPHY MONITORING H. Kim*, J. H. Lee, H. W. Ryu, J. S. Kim*, B. C. Lim, H. Hwang*, J. H. Chae, K. J. Kim, and Y. S. Hwang *Sepul National University Bundang Hospital, Seongnam-si, Korea; and Seoul National University Children's Hospital, Seoul, Korea
Purpose: We performed this study to evaluate the frequency, types, and ictal electroencephalography (EEG) findings of coexisting seizures in patients with infantile spasms at the onset of spasms. We also evaluated the effect of coexisting seizures on short-term seizure control. Method: We retrospectively reviewed the long-term video-EEG and electronic medical records of 109 patients (58 boys and 51 girls) diagnosed with infantile spasms at the Seoul National University Children's Hospital. Coexisting seizure types were classified according to the International League Against Epilepsy seizure and epilepsy classification. Ictal EEG findings were also reviewed. Short-term seizure control rates were compared between groups with or without coexisting seizures. Result: We identified 27 coexisting seizures in 24 of the 109 patients (22%). The most common type of seizure was generalized tonic seizure followed by myoclonic, focal tonic, tonic-clonic, hypokinetic, and versive seizures. Rates of preterm birth and birth asphyxia were significantly higher in patients with coexisting seizures. There was no significant difference in short-term seizure freedom (overall seizure-free rates in patients without coexisting seizures vs. those with: 29.2% vs. 11.1% at 2 months, 36.1% vs. 22.2% at 4 months, and 41.7% vs. 27.8% at 6 months). Seizure freedom was significantly lower in the symptomatic groups compared with non-symptomatic groups. Conclusion: Long-term video-EEG monitoring is required as an initial evaluation in patients with infantile spasms, especially when there are reports of coexisting seizures, or a history of preterm birth or birth asphyxia. Presence of coexisting seizures was not related to poor seizure control in the short-term treatment period. Conclusion: Significant variability in how geriatricians manage epilepsy was demonstrated. This may reflect the weak evidence base and thus poverty of specific guidelines for managing geriatric epilepsy. Extending this regional survey should increase its generalisability and provide an impetus for a more unified approach to its management in future.
p483 INCIDENCE OF FIRST ACUTE SYMPTOMATIC SEIZURES AND UNPROVOKED SEIZURES IN ADULT: A PROSPECTIVE, EPIDEMIOLOGICAL STUDY BASED IN CAPTIVE POPULATION IN ARGENTINA L. Romano, L. Sousa, G. Castellino, J. Zorrilla, F. Latini, P. Alvarez, M. Sanchez, A. Aleman, P. Loli, and S. Gonorazky Hospital Privado De Comunidad, Mar Del Plata, Argentina
Purpose: Seizure can be classified as acute symptomatic seizures (ASS) or unprovoked seizures (US), and this distinction is of clinical relevance in relation to treatment and prognosis. This importance, led us to conduct a prospective population-based incidence of first ASS and US in adult. Objectives: To determine the crude annual incidence rate, the specific rates according to age and sex based on the Official Argentinian National Census (OANC) of 2001 of the first episode of of ASS and US in adults. Method: From April 1, 2007 to March 30, 2009, we conducted a prospective epidemiologic study to identify patients with first episode of ASS and US in adults >65 years, in the state of Mar del Plata, Argentina. Result: The crude annual incidence rate of ASS in adults >65 years was 30.6 per 100.000 (95% CI: 22.244.5), 47.9 per 100.000 (95% CI: 26.2 80.5) in men and 22 per 100.000 (95% CI: 11.737.7) in women. In adults >65 the annual US incidence was 87.3 per 100.000 (95% CI: 68.9 109.1), 89.1 per 100.000 (95% CI: 58.2130.6) in men and 86.4 per 100.000 (95% CI: 64.3113.6) women. A statistically significant increase (p<0.0001) was observed when comparing rates among different age groups (6574 years, 7584 years and >85 years) for the ASS to the US. The adjusted annual rate to OANC was 22 ASS per 100.000 and 67.7 US per 100.000. Conclusion: The data presented show one of the few epidemiological prospective studies conducted in Argentina and Latin America, showing incidence rates similar to those observed in previous studies in developed countries.
p482 SURVEY ON THE MANAGEMENT OF EPILEPSY BY GERIATRICIANS S. L. Jones, and V. Adhiyaman Wrexham Maelor Hospital, Wrexham, UK
Purpose: Epilepsy is commonly encountered by geriatricians in clinical practice. However approaches to its management vary considerably. This survey aims to quantify this variability. Method: Members of the Welsh BGS were invited to participate in an online survey via a weblink. Questions covered referral patterns to specialist services, timing of anticonvulsant initiation, drug choice and use of neuroimaging and EEGs. Result: 37 responses were received: 21 from Consultants, 12 from SpRs and 4 from Associate specialists. 29.7% would initiate treatment after a first seizure. 64.9% would defer treatment until second. Table 1. (First line anticonvulsant choice for each epilepsy type (%)) Partial seizures Partial seizures with secondary generalisation Primary generalised seizures Sodium Valproate 40.5 54.1 62.2 Levetiracetam 32.4 32.4 24.3 Lamotrigine 21.6 18.9 18.9 Driving was the major determinant for referral to specialist epilepsy services: 56.8% of respondents rarely used EEGs. Reasons cited were inaccessibility of local services and low yield. 86.5% would request neuroimaging after first seizure.

p484 STATE OF BLOOD-BRAIN BARRIER AND NITRIC OXIDE METABOLISM IN PATIENTS WITH POSTTRAUMATIC EPILEPSY EARLY AFTER GENERALIZED SEIZURE O. Kukhlenko, and R. Kukhlenko Lviv National medical University, Lviv, Ukraine
Purpose: Neuron-specific enolase (NSE) is an enzyme detected in serum following structural damage of neuronal brain cells and increased permeability of blood brain barrier (BBB). Peroxynitrite anion (ONOO-) toxic metabolite of nitric oxide, is recognized to play important role in neuronal damaging and development of BBB dysfunction. The aim of our study was to evaluate the state of blood brain barrier and nitric oxide system in patients with posttraumatic epilepsy early after seizure occurrence.
142 Abstracts
Method: We examined 23 patients (14 males and 9 females) with posttraumatic epilepsy early (up to 24 hours) after generalized seizure and 14 patients with posttraumatic epilepsy (4 females and 10 males) and rare seizures more than 1 month after last seizure. All the patients survived mild or moderate traumatic brain injury and took carbamazepine as antiepileptic monotherapy. Concentration of NSE, ONOO- and activity of inducible nitric oxide synthase were estimated in blood plasma. Result: Received data revealed increase in plasma NSE concentration early after seizure 18.81.3 ng/ml while compared with control group (17.51.1 ng/ml, p Conclusion: There is an evidence of increased BBB permeability early after generalized tonic-clonic seizure in patients with post-traumatic epilepsy. BBB dysfunction is accompanied by increased serum levels of peroxynitrite and iNOS activity. establish possible relationship between location of arachnoid cysts and seizure foci. Method: Our study group comprised 130 patients, aged 1560 years, affected by simple partial and complex partial epilepsy with or without secondary generalization. They were diagnosed with epilepsy during 2010. and 2011. in our neurology department All patients had brain CTs and/or MRI scans and at least two interictal EEGs performed. The exact location of seizure focus was defined by history, semiology and EEG findings. Result: 9 patients of 130 with focal epilepsy also had large arachnoid cysts found on CT/MRI scans. The most common location of cysts was the middle fossa near the temporal lobe (5 patients), three patients had frontal lobe cysts and one patient had cyst located retrocerebellary paramedially. Only one patient with a left temporal lobe cyst had sezure focus and semiology related to the location of the cyst. Furthermore, one more patient with a temporal lobe cyst had a mirror EEG focus in the exact contralateral region of the brain. Consequently, seizure focus was related to the location of the cyst in only two of 9 patients (22%) which is consistent with results of other investigators Conclusion: Our data suggest that arachnoid cysts are most probably an incidental finding in patients with epilepsy unrelated to seizure focus in most of the cases but its unusually high incidence (7%) in these patients could be a possible target of investigation.
p485 ANALYSIS OF A GROUP OF PATIENTS WITH POSTSTROKE ACUTE AND REMOTE EPILEPTIC SEIZURES I. Chmielewska, A. B. Martinez Garcia, A. Moreno Rojas, M. Massot Cladera, M. C. De La Bandera Sanchez, S. Tur Campos, I. Barcelo Artigues, M. Mestre Sanso, and F. J. Molina Martinez Hospital Universitario Son Espases, Palma De Mallorca, Spain
Purpose: Stroke is a frequent cause of epileptic seizures in adults, however, there is limited information based in evidence. Our purpose is to analyse a group of patients with post-stroke acute and remote epileptic seizures, and use our conclusions to design a future longer prospective study. Method: This is a retrospective study in which we included haemorrhagic and ischemic stroke patients with epileptic seizures recorded in our stroke database. Epidemiological data, stroke aetiology, seizure subtype and time from stroke to the first epileptic seizure were registered. Result: From January 2009 to December 2010 a total of 378 patients was studied. 72.2% were men, mean age of 65.39 13.65 years. Haemorrhagic and ischemic stroke was diagnosed in 12% and 88% of the patients respectively. 3.9% of the patients suffered seizures during the first year after stroke, of which 67% had an ischemic stroke (40% cardioembolic, 20% due to large artery atherosclerosis, and 40% cryptogenic). Acute seizures (< 2 weeks after stroke) were detected in 1.5% of the patients, 67% with haemorrhagic stroke, without recurrences during the first poststroke year.2.4% of the patients developed epilepsy (considering a first remote seizure). Partial motor simple seizure was the most frequent type. Antiepileptic treatment was initiated in 93.3% of the patients and was maintained during the follow-up. Conclusion: Although our sample is reduced, the results are in accordance with other published series. It has permitted us to analyse our clinical management and to design a larger prospective study necessary for our community.
p487 COMPREHENSIVE INFORMATION IMPARTED TO PATIENTS WITH EPILEPSY AND COMORBIDITY AND DECREASED PREVALENCE OF ADVERSE TREATMENT EFFECTS. THE EDU-COM STUDY S. Beretta*, F. Gerardi, E. Beghi, and C. Ferrarese* *San Gerardo Hospital, Monza, Italy; and Istituto di Ricerche Farmacologiche Mario Negri, Milano,
Purpose: Epilepsy requires long-term drug treatment and is frequently associated with other clinical conditions and multiple drug-therapy in the elderly. The aim of this study is to provide evidence that a standardized educational strategy may positively affect adverse drug reactions, drug interactions and the quality of life in this epilepsy population. Method: The EDU-COM study is a multicenter, randomized, controlled, single-blind, pragmatic trial. Recruitment phase terminated in December 2011 after 180 consecutive adult epilepsy outpatients with chronic comorbidities and multiple-drug therapy have been recruited from 8 epilepsy centers nationwide and randomized to receive a comprehensive and standardized educational plan or usual care. All patients have been seen at baselines, at one month and at six months after admission. The primary outcome is the number of patients free from clinically relevant adverse treatment events or drug interactions at end of study. Secondary outcomes include health-related quality of life score changes using the QOLIE-31 questionnaire and the monetary medical costs, including the one-hour meetings with patients assigned to the experimental arm. Result: Interim analysis showed a significant effect of the standardized educational plan for the combined primary end-point at the end of follow-up (OR = 1.34). This effect appeared to be larger for patients with more severe side effects/drug interactions at baseline (OR = 1.66). The final results of the study will be presented. Conclusion: The EDU-COM study will provide novel and evidencebased data on the impact of educational strategies in the clinical management of epilepsy patients with comorbidities.
p486 UNUSUALLY HIGH INCIDENCE OF INTRACRANIAL ARACHNOID CYSTS AMONG PATIENTS WITH EPILEPSY UNRELATED TO SEIZURE ETIOLOGY D. J. Milivojevic*, and A. Z. Ilic *Medical Centre Petrovac, Petrovac, Serbia; and Health Center Studenica, Kraljevo, Serbia
Purpose: This retrospective study was conducted to assess an incidence of intracranial arachnoid cysts in patients with focal epilepsy and to
143 Abstracts
p488 INSOMNIA IN EPILEPSY PATIENTS. CLINICAL AND POLYSOMNOGRAPHIC CHARACTERISTICS. A RETROSPECTIVE STUDY A. Rodriguez*, and E. Koziorynska *New York Sleep Institute, New York, NY, USA; and SUNY Downstate Medical Center, Brooklyn, NY, USA
Purpose: Patients with epilepsy have multiple sleep problems, including insomnia. Mood disorders are a significant co-morbidity in epilepsy. There is a high prevalence of insomnia in patients with mood disorders. The clinical and polysomnographic (PSG) characteristics of epilepsy patients with insomnia have not been described. Method: Medical records of all adult epilepsy patients seen at Sleep Disorders Center were reviewed over 6 months. All subjects presenting with insomnia were selected. Consecutive non-epileptic insomnia patients were selected as controls. Result: Seventeen adult patients with epilepsy were included. Among epilepsy patients, 76.7% were women, mean age was 40.7 years and 58.8% had partial seizures. Seventy-six percent of patients had troubles to fall asleep and 68.7% had troubles to stay asleep (there was no statistically significant difference with controls). 52.9% of patients were using a sleep medication. Zolpidem was the most commonly used medication among patients and controls (64.7% and 76.5%), followed by melatonin (41.2% and 41.2%). Patients with epilepsy had a statistically significant higher percentage of depression compared to controls (52.9% vs. 17.6%, p=0.028). PSG showed a mean sleep efficiency of 69.0% with a mean sleep latency of 48.8 minutes among epilepsy patients. These results did not differ from controls. Sleep disordered breathing was present in 50.0% of patients and 44.4% of controls. Conclusion: Epilepsy patients with insomnia have a higher prevalence depression compared controls. There is a high percentage of use of sleep medications among these patients. The clinical and PSG characteristic did not differ when compared with controls. headache and dizziness and in most of the patients lambda waves appeared during 3D. Conclusion: In this running study, until now, an increase of ED was detected in 3 of 84 children with epilepsy (3.6%) while watching 3D. The reduction of ED during 3D can be interpreted as an increase of alertness. A seizure during 3D was not observed. The risk to provoke a seizure while watching 3D is apparently low and does not seem to be a matter of technology (3D or 2D), but rather a matter of the video content (for example particular colors or repetitive figures). A high percentage of the patients however reported vegative symptoms like in motion sickness during 3D.
p490 SCREENING OF SLEEP DISORDERS IN THE EPILEPSY PATIENTS M. E. Contreras Pinto, T. Rodriguez Riquelme, R. Julliet Perez, J. A. Gonzalez Hein, and R. Galeno Trewelas Hospital DIPRECA, Santiago, Chile
Purpose: The reciprocal influence between epilepsy and sleep disorders can worsen the prognosis for both processes. Was raised as a main objective of the present study, to screen the sleep disorders (SD) in patients with epilepsy and so be able to design an intervention plan. Method: Were surveyed 37 patients and 41 controls, with similar characteristics in gender and age. The questionnaire included, among other variables, Epworth sleepiness scale and SA-SDQ for sleep apnea. Result: 34% of epileptic patients has some sleep disorders (29% in controls, p<0.05). The most frequent one was symptoms of insomnia (40%), followed by the bruxism and restless legs syndrome. A 29% of patients have SA-SDQ altered suggestive of sleep apnea. A 13% recognized time of night-time sleep insufficient and 16% excessive daytime sleepiness. Epileptic patients with good control of crisis were correlated with better sleep hygiene (52% vs 25%), lowest sense of daytime sleepiness (36% vs75%) and lower BMI (26vs30) compared with patients with worst control of crisis. Conclusion: The frequency of sleep disorders is high, even higher than the control population, especially insomnia and probably sleep apnea. Data that allow us to increase the index of suspicion and intervene in these patients.
p489 3D-TELEVISION AND THE RISK OF SEIZURES IN CHILDREN L. Navarro-Ramirez*, H. Plischke, J. Riess, C. Bumel, C. Von Stlpnagel, M. Staudt, and G. Kluger *Zentrum fr Kinder und Jugendliche Inn Salzach, Alttting, Germany; Generation Reseach Program, Bad Toelz, Germany; and Schn Klinik Vogtareuth, Vogtareuth, Germany
Purpose: In 1997 approximately 685 Japanese children were hospitalized by suspected epileptic seizures after watching a Pokemon series. In 2010 a 42-year-old man in Taiwan died while watching the 3D epic (3DE) Avatar. The risk of seizures while watching 3D in patients with epilepsy has not been systematically examined yet. Method: After a 20 min Routine-EEG with Photo stimulation (PS) runs a 15 min Video-EEG, meanwhile was the 3DE Ice Age watched. A 50 inches 3D- Plasma-TV with 3D-Shutter glasses was used in a 9-m2 room with a 2 m watching distance. Each EEG was independently from 2 physicians (LN-R, GK) visual evaluated. Result: To date 150 patients (77 male, mean age 12) were analyzed. 84 patients had epilepsy. 15 patients presented a photo paroxysmal reaction (PPR). 1 patient with epilepsy (4 seizures/day) had a seizure shortly after 3D. 3 patients with idiopathic generalized epilepsy had an increase of epileptic discharges (ED). In all other patients neither seizure could be provoked, nor did the ED increase while viewing 3D-TV. 10 patients presented a reduction from of ED. 25 patients complained about nausea,
p491 SEIZURES AND ALCOHOL S. Grabova, S. Mijo, I. Zekja, and J. Kruja UHC Mother Theresa, Tirana, Albania
Purpose: The association of seizures and alcohol abuse is well established (Lennox, 1941). Seizures, epilepsy and alcohol use are complexly interrelated, and research in this field suffers from a lack of unanimity in terminology and definitions. We all know that seizure constitutes one of the most frequent and challenging medical complication of alcohol abuse. Method: We studied the patients presented with acute seizures in neurology emergency room of University Service Center Mother Theresa of Tirana, during the last year. Result: We identified 62 patients with acute seizures (37 males and 25 females). 40 patients had SE (30 of them [75%] were previously diagnosed with epilepsy). 10 patients (16.1%) had seizures related to alcohol use (4 patients) or withdrawal (6 patients). All of them were males aged from 3048 years old (mean age 34.4 years old). A detailed analysis of alcoholic seizures is done. A review of the literature on alcohol effects on seizures is presented too.
144 Abstracts
Conclusion: The association of seizures and alcohol abuse is well established (Lennox, 1941). Seizures, epilepsy and alcohol use are complexly interrelated, and research in this field suffers from a lack of unanimity in terminology and definitions. We all know that seizure constitutes one of the most frequent and challenging medical complication of alcohol abuse. consecutive patients presented in emergency department. AP, daily maximum, minimum and range between maximum and minimum of AP were correlated to daily number of seizures per patient. Result: In the period of interest a total of 1721 epileptic seizures (23% generalized tonic-clonic seizures - GTCS) occurred in 265 patients in video-EEG monitoring unit. In the same period 5053 patients presented to the ED due to 5120 epileptic seizures (45% GTCS). We found weak negative correlation between number of seizures per patient and values of AP in video-EEG monitoring unit (Spearman rank coefficient -0.07; p<0.01). We also found a bit stronger negative correlation between number of seizures per patients and values of AP in patients presented in ED (Spearman rank coefficient -0.11; p<0.01). Very similar and statistically significant results were demonstrated with following variables: daily mean AP, maximum or minimum, and range between maximum and minimum of AP change in both clinical settings. Conclusion: We found mild evidence to suggest lower atmospheric pressure made seizure occurrence more likely in video-EEG monitoring unit and more general population of patients presenting at ED.
p492 ARE BENZODIAZEPINES PROTECTIVE AGAINST PROPXYPHENE ABUSE ASSOCIATED SEIZURES S. Kaushal, M. Jain, S. Arora, and G. Singh Dayanand Medical College and Hospital, Ludhiana, India
Purpose: To determine the pattern of substance abuse associated with seizures Method: The study was conducted over a period of 15 months in patients attending epilepsy clinic at the Institution. Patients with history of substance abuse, consenting to participate in the study, were evaluated to determine the details of substances abused, resultant seizures, temporal relationship of seizures with substance abuse and drug therapy. In addition the patient demographics were recorded. Result: Among 42 patients fulfilling the criterion and consenting to participate in the study, 64% were in the age group of 1635 years. All the subjects were males (100%). Most of them had history of multiple substance abuse. Among the single substances abused, alcohol was the commonest (72%). Among Opiates, Propoxyphene (47%) was most commonly abused. Generalized Tonic Clonic (GTC) Seizures was the commonest presentation followed by a combination of GTC and Myoclonic seizures (seen specifically in propoxyphene abusers). The seizures were observed during withdrawl with abuse of alcohol and benzodiazepines while seizures were during intoxication phase with opiates. Concomittant use of benzodiazepine and propoxyphene was protective against withdrawl seizures observed with propoxyphene. Conclusion: Alcohol was the commonest substance abused resulting in seizures. GTC seizures was the commonest semiology. Among opiates, propoxyphene was the commonest substance abused. The characterstic semiology in these patients was myoclonic jerks preceeding GTC seizures. Concomittant Benzodiazepine use with propoxyphene was protective in these patients. Benzodiazepines can be used as a treatment option in patients presenting with propoxyphene abuse associated seizures

p494 FACTORS INFLUENCING QUALITY OF LIFE IN 160 SUBJECTS WITH EPILEPSY AND THEIR CAREGIVERS A. Alam, M. M. Mehndiratta, S. Pandey, and R. Nayak G.B Pant Hospital, New Delhi, India
Purpose: To assess the quality of life (QOL) of People with Epilepsy (PWE) and their caregivers using the QOLIE-31and SF36 Instruments and to study the predictors of QOL. Method: This study was conducted at G. B. Pant Hospital using a cross sectional design. Total 160 subjects with epilepsy (all types) of at least one year duration and their care givers of age range 18 to 60 years were included. Detailed history and demographic characteristics were recorded in a structured proforma. Assessment was done by using adapted version of QOLIE 31 (Quality of Life in Epilepsy Subjects 31) for epilepsy subjects and SF 36 (Short Form Health Survey 36 version 2) for their care givers Result: There was male preponderance and subjects (78.75%) were young (age<30 yrs). Generalized seizure (65.63%) was the most common type of seizure and majority of subjects (74.37%) had epilepsy of less than 10 year duration. Low education and socioeconomic status, earlier age of onset, higher frequency of seizures, more duration of epilepsy and less time passed since last episode of seizure and polytherapy were predictors of lower quality of life in subjects and care givers. QOL was found to be low if care giver was female (mother or wife of subject). Conclusion: Patients with epilepsy as well as their caregivers have poor quality of life which may be related to disease per se, drug therapy and a variety of social factors. Their proper assessment and relevant management should be included in the holistic epilepsy care.
p493 DOES ATMOSPHERIC PRESSURE CORRELATES WITH SEIZURE FREQUENCY IN EPILEPSY MONITORING UNIT AND EMERGENCY DEPARTMENT? A. J. Ristic*, D. Jovanovic, G. Trajkovic, S. M. Jankovic*, N. M. Vojvodic*, M. M. Kovacevic*, V. L. Bascarevic, and D. V. Sokic* *Neurology Clinic, Belgrade, Serbia; Regional Hospital Zemun, Belgrade, Serbia; Medical School Belgrade University, Belgrade, Serbia; and Clinic of Neurosurgery, Clinical Center of Serbia, School of Medicine, University of Belgrade, Belgrade, Serbia
Purpose: To investigate correlation of the seizure frequency in patients undergoing long-term video EEG monitoring and patients presented in emergency department (ED) with atmospheric pressure (AP) changes. Method: Historical automated AP data (January 2008November 2011) from weather station in the Belgrade area (100m aside of hospital facilities) were correlated to seizure frequency in: 1) consecutive patients undergoing long-term video EEG monitoring at our institution and 2)
p495 EMPLOYMENT OF PEOPLE WITH EPILEPSY FROM THE PERSPECTIVE OF PATIENTS, NEUROLOGISTS AND THE GENERAL POPULATION ska*, and J. Je B. Majkowska-Zwolin drzejczak *Foundation of Epileptology, Warsaw, Poland; and Medical Centre for Postgraduate Education, Warsaw, Poland
145 Abstracts
Purpose: To present the profile of employed epileptic patients (EP) in Poland and opinions of patients, neurologists and the Polish population about employment of persons with epilepsy. Method: A questionnaire-based study was carried out in 2009 all over Poland and included: EP 1865 yrs (995), neurologists (179) and a representative sample of Poles (1042). Computer-assisted personal interviews and paper-and-pencil questionnaires were used. The International Standard Classification of Occupations (ISCO) was used to classify jobs. Result: Out of 995 EP, 49% were employed and 51% did not work at the time of the survey; 67% of them had full time jobs. There were no gender differences. Most of the patients worked in the following occupational groups (according to ISCO): professionals (23.0%) clerical support workers (21.8%), technicians and associate professionals (20.4%). Persons with higher education and with good control of seizures ( 1 seizure/ year) had a better chance of employment, OR=2.92; 95% CI 2.203.88 and OR= 1.85; 95% CI 1.342.56 respectively. 25% of EP, 28% of neurologists and 56% of Poles expressed the opinion that every EP can work, and 63%, 72% and 29%, respectively expressed the opinion that they can work with some limitations. In the opinion of 11% of EP and 8% of Poles, EP should not work at all. Conclusion: Persons with epilepsy with good control of seizures and better education have a better chance of employment. Choice of occupation reflects patients medical limitations. Poles have a generally positive attitude toward the employment of persons with epilepsy. stigma in this society. From this rises the importance to promote community-based educational programs aimed at reducing the stigmatization process that may represents one of the major obstacles to the management of epilepsy.
p497 IMPACT OF STIGMA ON QUALITY OF LIFE OF PATIENTS WITH REFRACTORY EPILEPSY E. I. Viteva-Velkova Medical University - Plovdiv, Plovdiv, Bulgaria
Purpose: To assess impact of stigma on life quality of Bulgarian patients with refractory epilepsy. Method: We studied 70 patients with refractory epilepsy who were 18 65 years of age, without cognitive decline, progressive somatic or neurological disease or recent seizures. All participants fulfilled QOLIE-89 and a 3-item stigma scale with an additional question about the patient's opinion on the reason for the unusual attitude of people. Result: The patients were with a mean disease duration 25.071.32 years. 17 (24.29%5.13) of them had partial seizures, 16 (22.86%5.03) generalized seizures and 37 (52.865.97) polymorphic ones. Most often they had high weekly (45.71%) or monthly (30%) seizure frequency despite the prescribed polytherapy in 90% of cases. The greatest percentage of them (40%5.86) had symptomatic epilepsy. We found out stigmatization in 44% of participants, 29% were severely stigmatized. The most frequently defined reason (by 58.54%) was people's fear of seizures because of inability to act adequately. Stigmatization had a negative impact on the total value of QOLIE-89 (47.80 as a T-value) as well as all subscales of QOLIE-89 (P<0.01) with the exception of Change in health and Sexual relations P>0.05. The highest percentage of stigmatized patients who made very low and low assessments was for the subscales Health perceptions (82.9%), Emotional well-being (71.5%), Memory (63.4%) and Health discouragement (62.5%). All assessments were negatively correlated with stigmatization severity. Conclusion: All aspects of life quality of Bulgarian patients with refractory epilepsy correlate negatively with the level of their stigmatization.
p496 EPILEPSY-ASSOCIATED STIGMA IN BOLIVIA: A COMMUNITY BASED STUDY AMONG GUARAN POPULATION. A ILAE/IBE/WHO GLOBAL CAMPAIGN AGAINST EPILEPSY REGIONAL PROJECT E. Bruno*, A. Bartoloni, V. Sofia*, F. Rafael3,4, D. Magnelli, S. Padilla, G. Quattrocchi*, F. Bartalesi, H. Segundo**, M. Zappia*, P. Preux3,4, and A. Nicoletti* *University of Catania, Catania, Italy; Careggi Hospital, Firenze, Italy; School of Medicine, Institute of Tropical Neurology, Univ. Limoges, Limoges, France; CHU Limoges, Limoges, France; Teko Guaran, Camiri, Bolivia; and **Santa Cruz, Camiri, Bolivia
Purpose: Epilepsy is associated with a significant burden of stigma especially among traditional society. Stigma has been shown to have a negative effect on management of people with epilepsy (PWE) representing one of the major factors that contribute to the burden of epilepsy. The current study was designed to assess stigma perception among Guaran population in order to identify the main determinants of the stigmatization process on which it should be act in the attempt to overcome stigma related to epilepsy and its consequences. Method: A group of PWE, a group of relatives of PWE, a group of health-care personnel and a group of students living in Guaran communities in Bolivia were invited to complete the Stigma Scale of Epilepsy (SSE) questionnaire. Result: One hundred thirty-two people completed the questionnaire showing a moderate perception of stigma among these communities. The main determinants of stigma identified in this population were: the fear linked to loss of control, the feelings of sadness and pity toward PWE and the difficulties faced by PWE in the professional and relationship fields. Others predictors of stigma were level of education and type of seizure for PWE. Conclusion: Our study pointed out that, among Guaran, PWE face difficulties in everyday life because of epilepsy related stigma and attested how cultural aspects and lack of knowledge contribute to perpetuate
p498 EXPERIENCE OF EPILEPSY IN A SENEGALESE SERIES OF PATIENTS L. B. Seck, K. Toure, M. Ndiaye, L. Gueye, A. G. Diop, and M. M. Ndiaye Fann Teaching Hospital, Dakar Fann, Senegal
Purpose: To assess epilepsy impact on daily life of patients suffering from it. Method: Prospective study on patients suffering from epilepsy the neurological department of Fann teaching hospital in Dakar. Result: One hundred and twenty three patients have been questionned. Mean age was 22.5 years, with 55.3% males and 44.70% females. Seventy one point five per cent think that epilepsy is an organic disease, 6.5% link it to evel phenomenon, while 22% don't know how to qualify it. Sixty four point two per cent of patients perfectly comply with the treatment, 29.3% do not regularly take it, 6.5% have interrupted it. For the 74% of patients that answered to this question, therapy is not considered as restricting. Eighty four point five per cent of patients maintain to have been improved by the therapy. The main side effects of treatment were neurological and genital. Only 57.32% of school age patients were provided with schooling, with decreasing of school efficiency under therapy in 40.42%. Bearing of the treatment costs is provided by parents for
146 Abstracts
63.4% of patients, the patients themselves for 33.3%, by friends or social assistance for 3.3%. Forty two point twenty seven per cent appeal to traditional practitioner, with failure in 86.53% of cases. For 53.55% of patients, close contacts are informed of the disease, and reactions are rather pejorative in 54.54% of cases. Conclusion: Epilepsy still keeps pejorative connotation in african societies. Side effects of therapy add up to the impact of the disease on daily life, facilitating impairment of quality of life. (especially patients with lower qualification), social isolation (exclusion, fear of the disease and stereotypes by others) and problems with claiming disability benefits. 70% of patients in our sample reported that medications do not fully manage their epilepsy symptoms. Most of the patients however perceive social problems associated with the condition to have much more severe impact on their quality of life than symptoms associated with epilepsy. As a part of the study findings from inductive analysis of focus group transcripts were compared with medical classification of severity of epilepsy symptoms. Conclusion: In conclusion, the results suggest that there is an urgent need to create a framework for providing social services and support to patients with epilepsy. Moreover, the welfare system in Slovakia is in the critical need of readjusting its criteria of providing benefits to such patients.
p499 A SURVEY OF MEDICAL ASSOCIATION MEMBERS IN THE SAN-IN REGION ON THE MEDICAL TREATMENT OF PEOPLE WITH EPILEPSY S. Yoshioka, S. Takama, and M. Saiga Tottori University, Yonago, Japan
Purpose: To carry out the medical cooperation necessary for people with epilepsy (PWE), it is important to clarify the number of PWE and the actual condition of treatment for PWE. Therefore, we investigated the medical situation of PWE by administering questionnaires to all the members of the medical association in the San-in region. Method: A questionnaire asking about clinical department, workplace, number of patients with epilepsy, medical society and information source on epilepsy medical care and welfare was distributed to both the Tottori and Shimane medical association members in 2010, and a total of 886 (35.1%) responses were collected. Result: Of the respondents, 336 (37.9%) engaged in the clinical treatment for PWEs. In the clinical department and workplace of the members, there were the highest proportions of internal medicine work in clinic. As members of a medical society, most (41.1%) belonged to the Japanese Society of Internal Medicine, while 30 (8.9%) belonged to the prefecture's medical association alone. As an information source on epilepsy medical care and welfare, most used many magazines concerning medicine, while 73 (21.7%) doctors had hardly obtained information about epilepsy treatment. The rate of prevalence for epilepsy in the San-in region was estimated to be 8.42 per 1000 for 2010. Conclusion: The present results indicate that it should be important to carry out medical cooperation between general doctors engaged in the treatment of PWEs and epilepsy medical specialists. This study was supported by the Japanese Epilepsy Research Foundation.
p501 PERCEPTION OF EPILEPSY-RELATED HANDICAP IS GREATER IN NAVE POPULATION ACCORDING TO A FRENCH WEB-BASED SURVEY INVOLVING MORE THAN 2000 PERSONS S. Hamelin, L. Vercueil, and A. Depaulis Grenoble Institut de Neurosciences, La Tronche, France
Purpose: Our aim was to study knowledge and perception of epilepsy in a large cohort, and to compare their answers according to their relation to epilepsy. Method: We developed a web anonymous auto-questionnaire (35 questions) proposed to epileptic patients and independent Email diffusion lists, in France. Answers were collected during a two-months period in 2011. Result: 2047 responses were collected (1421 females and 626 males, mean age 2635 y.o.). 17% were personally concerned by epilepsy (directly concerned, DC), 67% were indirectly concerned (IC), and 16% were not concerned at any level and did not know persons with epilepsy (not concerned, NC). Self-evaluation of epilepsy knowledge was low (3.2 (NC) to 4.5/10 (DC)). The possibility that epilepsy could occur in neonates or in elderly was mostly unknown, especially in group NC (55 and 39%). Treatment was thought to be more restricting by group DC, and 41% of them reported mandatory life-long treatment. The perception of the ability of epileptic people to perform all aspects of daily life was globally good, mostly up to 4/5, but always better in group DC as compared to NC. The more reported handicaps in epilepsy were fear of seizure, fear of loss of self-control, and social stigma. Conclusion: Auto-evaluation of knowledge regarding epilepsy is low, according to this web-based survey, underscoring the need for further education of global population. Interestingly, the perception of epilepsyrelated handicap in epilepsy is the greatest in people not concerned by epilepsy.
p500 EXPLORING QUALITY OF LIFE IN SLOVAK EPILEPSY PATIENTS: A FOCUS GROUP STUDY V. Donth*, and R. Masaryk *F.D. Roosevelt Teaching Hospital, Banska Bystrica, Slovak Republic; and Faculty of Education, Comenius University, Bratislava, Slovak Republic
Purpose: The objective of the study was to identify perceptions of quality of life in patients with epilepsy focusing on their experience with the condition and experience with treatment. Method: The methods used were focus groups (semi-structured discussions moderated by a trained psychologist) and questionnaires. In total 11 focus groups were conducted with 54 patients. The average age was 38 years (min. 18, max. 72), 56% women and 44% men. Result: Three areas where epilepsy mostly interferes with the quality of life as reported by patients were the problem of finding employment
p502 CAN SOCIAL SUPPORT SERVE AS A MEDIATOR BETWEEN ILLNESS PERCEPTION AND QUALITY OF LIFE IN PATIENTS WITH EPILEPSY? T. Bar-Adon*, T. Krulik, I. Bluvstein, and M. Neufeld *Tel-Aviv Medical Center, Tel-Aviv, Israel; Tel-Aviv University, Tel-Aviv, Israel; and Tel-Aviv Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
Purpose: To evaluate social support (formal and informal) as a potential mediator between disease perception and Quality of Life (QoL) in patients with epilepsy.
147 Abstracts
Method: The sample consisted of 80 patients with epilepsy that were recruited from a tertiary epilepsy center. There were 44 females and 36 males, aged 3613.5 years. Data were collected via 4 questionnaires: socio-demographic, which also included disease severity on a 110 Likert scale, brief illness perception, social support, and the Quality of Life in Epilepsy (QOLIE-31). Result: Illness perception had a significant negative correlation with QoL (r=-0.597, p<0.001). There was no significant correlation between social support and QoL (r=0.163, p=0.148), however, informal (nuclear family) social support positively and significantly correlated with QoL (r=0.315, p=0.004). Social support did not emerge as a mediator between disease perception and QoL (b=0.64, p=0.45). Conclusion: Although in our study, social support could not be considered a mediator between illness perception and QoL in patients with epilepsy, there was a positive effect of nuclear family support on their QoL. This finding may be a valuable contribution in the construction of guidelines for enhancing the QoL in this patient population. Purpose: Ictal kissing has been described in the literature. Six cases were reported and associated with TLE and lateralizing to the non-dominant hemisphere Method: A case of ictal kissing was identified. The aim is to demonstrate and discribe the clinical, electro neurophysiologic, surgical procedure, histopathological and imaging data. Result: 29 year sold right-handed female, who has history of epilepsy for the last 10 years. The patient has no history of febrile convulsions. She has history of an aura of fear followed by automatism of the right hand and left dystonic posturing and lip smacking. This is usually followed by prolonged emotional gestures, hugging and kissing her relative and the attendant nurse. The patient has frequency variable from 12 per month. MRI of the brain showed right small cortical and subcortical lesions at the right inferior frontal lobe with gliosis, but without mass effect. The lesion is located directly anterior of the insular gyrus, and most inferiorly of the inferior frontal gyrus. The hippocampi looked symmetrical. The PET scan showed hypometabolism of the right temporal lobe. Neuropsychology of the patient was showing deficit in her nonverbal memory. In the Epilepsy unit, 5 push-button events were recorded. The subdural electrodes showed periodic poly spikes discharges over the right inferior frontal region followed by high amplitudes spikes over right mesial temporal lobe leads. The offsite of the ictal discharges are usually at the right frontal strips. Right standard temporal lobectomy with amygdalohippocampectomy, with corticectomy and lesionectomy of the right inferior frontal under neuronavigation guidance was performed. The patient continued seizure free. Histopathology of the hippocampus did not show mesiotemporal sclerosis. The inferior frontal lesion histopathology was compatible with gliosis. Conclusion: Our case report supports the findings of the few reported cases of the ictal kissing behavior lateralized to the non-dominant hemisphere. However, the inferior frontal lobe gliotic lesion is a new finding of the affectionate kissing automatisms and may provide a novel understanding of this stereotyped ictal emotional behavior.
p503 INVESTIGATION INTO REPRESENTATION IN FILM OF FIRST PERSON SUBJECTIVE EXPERIENCE OF A GROUP OF PEOPLE WITH EPILEPSY S. Anderson University of the Arts London, London, UK
Purpose: To identify underlying patterns in modes of expression of the subjective experience of people with epilepsy in a Wellcome Trust funded film What's the Time Mr Wolf? Method: In an interdisciplinary collaboration motivated by studies of the representation of epilepsy in film and television (Baxendale S. The Lancet Neurology 2003 Volume 12: Issue 12: 764770) ten people with epilepsy participated in filmed discussion and accounts of first person subjective experiences of epilepsy. Documentary and dramatized elements are examined as part of an investigation into the use of film as a medium to articulate the first person subjective experience of the condition. Result: The perceived third person reactions to epileptic seizures dominated accounts by the participants. For the most part, the first person subjective was displaced by the other. The observer or witness - the third person - largely determined the narrative voice of the first person subjective experience of the seizure. Conclusion: Findings highlight the need to increase public awareness of epilepsy, given the typically exaggerated and negative third person reactions to the altered sense of self during a seizure. Strategies of using film to construct narratives with positive mechanisms for people with epilepsy are proposed.
p505 VARIANTS OF TRANSFORMATION OF EPILEPTIC SEIZURES A. Dubenko, O. Vasilieva, and D. Kovalenko Institute Neurology, Psychiatry and Narcology AMS of Ukraine, Kharkiv, Ukraine
Purpose: We tried to identify and study the transformation of seizures. Under the term of transformation of epileptic seizures (TES), in the present study were examined changes in clinical symptoms and changes in the type of attack that could indicate a deterioration of clinical status and progression of the disease. Method: The presence of TES studied at 60 patients. 32 patients were had symptomatic epilepsy, 28 cryptogenic. This clinical group was selected after supervision and analysis 320 patients with epilepsy (130 symptomatic and 190 cryptogenic). Age of patients was 2055 duration of epilepsy no less than 1year. Result: In adult patients can be observed TES. TES are presented for patients with symptomatic partial epilepsy more frequent than in patients with cryptogenic epilepsy. Changes in clinical seizures, which were characterized by disease progression, increase of mental and neurological disorders, and deteriorating quality of life of the patient, transformation refers to the negative. If the change in the clinical picture of seizures was accompanied by improvement of the run of the disease - recorded positive transformation. 32patients had negative transformations, 28 - positive ones. Conclusion: The study of the character TES is an important, accessible and objectified criteria for assessing of epilepsy activity, the adequacy of antiepileptic therapy, the subsequent prognosis.

p504 ICTAL KISSING WITH COMPLEX PARTIAL EPILEPSY AND INFERIOR FRONTAL GLIOSIS A. Alsemari, F. Alotaibi, and S. Baz King Faisal Specialist Hospital & Research Centr, PO box 3354, Saudi Arabia
148 Abstracts
p506 CLINICAL, VIDEO-EEG AND NEUROIMAGING STUDY OF DRUG-RESISTANT FOCAL EPILEPSY ASSOCIATED WITH HAMARTOMA OF THE FLOOR OF THE FOURTH VENTRICLE G. Rubboli*, L. Volpi, M. Maffei, F. Marliani, P. Riguzzi, S. Zoboli, G. Faggioli, F. Santoro, E. Pasini, and R. Michelucci *Epilepsihospital, Filadelfia, Dianalund, Denmark; IRCSS Institute of Neurological Sciences, Bologna, Italy; and Nuclear Medicine Unit, Bologna,
Purpose: Hamartomas of the floor of fourth ventricle (HFFV) are extremely rare entities that can be associated with repetitive attacks of hemifacial spasm. Intralesional EEG recordings of epileptic discharges and ictal SPECT suggested seizure onset within the hamartoma. This study aimed to extensively investigate the clinico-neurophysiological-neuroimaging features of a patient with drug-resistant focal epilepsy associated with HFFV. Method: A 20 years-old female patient with drug-resistant focal motor seizures of the right hemiface, occurring several times per day since 6 months of age was admitted to Epilepsy Monitoring Unit for evaluation of a drug-resistant focal epilepsy. A detailed clinical history was taken. She underwent awake and sleep EEG/polygraphy, long-term video-EEG monitoring (LTVEEG), 3 Tesla MRI (3T-MRI), interictal and ictal SPECT, neuropsychological assessment. Result: Interictal awake and sleep EEG/polygraphy did not show epileptiform abnormalities; during sleep, polygraphy revealed periodic muscle twitches of the right orbicularis oris without EEG correlate. LTVEEG showed focal seizures, occurring several times per day characterized by right eye blinking, myoclonic twitches of the right hemiface sometimes spreading to the neck with right head deviation. Ictal EEG did not show clear-cut epileptiform discharges (Video-EEG data will be presented). 3T-MRI showed right HFFV. Interictal/ictal SPECT was inconclusive. Neuropsychological assessment was unremarkable. Conclusion: Our data contributes to furtherly define the rare condition of focal epilepsy associated with HFFV. Ictal LTVEEG data supported the hypothesis of the main activation of brainstem nuclei by the epileptic discharge originating from HFFV, with a mechanism possibly analogous to hypothalamic amartoma. (MT) dynamics, in vitro. C-terminally FLAG-tagged tubulin expression constructs were transfected into HEK293 and PC12 cell lines. Result: Three novel and one recurrent TUBA1A sequence variations were identified in the LIS patient cohort and one genetic variant was identified in a patient with PMG. Four novel TUBB2B sequence variants were also identified in PMG patients. All variants identified were heterozygous de novo that translated into missense amino acid substitutions. Incorporation of these mutants into the MT cytoskeleton was observed in comparison to wild-type, followed by morphometric analysis and MT polymerisation assays. Homology models of tubulin mutants were generated to predict the consequences of the residue substitutions on protein conformation. Conclusion: TUBA1A and TUBB2B mutations are present in cohort index-cases confirming their role in cortical malformation syndromes. We present significant evidence of in silico and in vitro data confirming the protein damaging effects of these mutations.
p508 A PORTABLE DEVICE FOR INVESTIGATING AUTOMATED SEIZURE ABATEMENT IN HUMANS USING ELECTRICAL STIMULATION A. Lai*, M. Cook, T. S. Nelson*, D. B. Grayden, C. E. Williams*, and P. Blamey* *Bionics Institute, East Melbourne, Vic., Australia; and The University of Melbourne, Melbourne, Australia
Purpose: To develop a portable device to investigate automated seizure abatement using electrical stimulation in patients with refractory epilepsy undergoing intracranial EEG monitoring for pre-resective assessment. The portable system simplifies deployment and enables data collection from multiple epilepsy centres to mitigate logistical limitations with conducting research on these patients. These limitations include a relative small number of patients being assessed per annum at any centre due to the resource intensiveness of these studies, with assessment periods often limited to one week to minimise infection risk, research paradigms are only initiated after sufficient clinical information is obtained, and patients may have few seizures during monitoring. Method: A portable device was specifically designed and constructed to investigate automated seizure abatement using electrical stimulation in epilepsy patients. The research system consists of a wireless EEG acquisition device, a custom built stimulator with a switch array that can route individual electrode connections to either the EEG acquisition device or the stimulator, and a tablet PC that runs the EEG acquisition software and seizure detection to trigger the therapeutic stimulation, as well as controlling the stimulation paradigm. The device was designed to be compatible with different electrode configurations and capable of reprogramming for evaluating different stimulation/detection paradigms. Result: The portable research device has evolved from our modular trolley mounted research setup and serves as a proof of concept for an implantable automated seizure abatement device. Conclusion: A portable device has been developed to simplify and enhance further investigations on automated seizure abatement in humans using electrical stimulation.
p507 TUBULIN GENES IN HUMAN DISORDERS OF CEREBRAL CORTEX DEVELOPMENT T. D. Cushion*, J. G. J. Mullins*, S. Chung*, R. J. Harvey, W. B. Dobyns, D. T. Pilz, and M. I. Rees *Swansea University, Swansea, UK; UCL, London; Seattle Children's Hospital, Seattle, WA, USA; Wales Epilepsy Research Network, Swansea, UK; and Institute of Life Science, Swansea, UK
Purpose: The development and correct function of the mammalian cerebral cortex is dependent on the precise arrangement of neurons to assemble its characteristic laminar structure. Lissencephaly (LIS) and Polymicrogyria (PMG) are devastating neuronal migration disorders comorbid with severe epilepsy, intellectual and physical disabilities. These disorders arise when the regulation of cell migration in the developing cerebral cortex is disturbed. This study describes the role of tubulin genes (TUBA1A and TUBB2B) in disorders of cortical development. Method: LIS and PMG patient DNA from UK and US Centres was screened for TUBA1A and TUBB2B mutations by direct sequencing. Variants were functionally analysed to assess the effects on Microtubule
p509 FOCAL CORTICAL DYSPLASIA TYPE IA AND PARVALBUMIN STAINING IN TEMPORAL LOBE EPILEPSY G. Kuchukhidze*, I. Unterberger*, G. Luef*, M. Ortler*, A. Wieselthaler-Hlzl*, A. J. Becker, E. Trinka, and G. Sperk* *Medical University of Innsbruck, Innsbruck, Austria; Institute for Neuropathology, Bonn, Germany; and Paracelsus Medical University, Salzburg, Austria
149 Abstracts
Purpose: Alterations in GABA-ergic cortical neuronal system have been reported in FCD type Ia, a malformation of cortical development associated with of pharmacoresistant epilepsy. We aimed to analyse parvalbumin (PV)-immunoreactive interneurons in 19 patients with pharmacoresistant temporal lobe epilepsy (TLE) and FCD type Ia affecting temporal lobe. We compared our findings with those in cortical surgical specimens of 20 TLE patients who underwent the resection of anterior two-third of a temporal lobe due to hippocampal sclerosis (TLE-HS) as well as 8 post-mortem controls. Method: Routinely stained slides and serial sections for neuron-specific nuclear protein (NeuN) and PV were analysed. The density of inhibitory PV-immunoreactive interneurons was quantitatively assessed in all patients and controls by using a two-dimensional cell-counting technique. The following three parts of temporal cortex and white matter were assessed separately in all groups: 1) cortical layers 1 through 4, 2) cortical layers 5 and 6, and 3) subcortical white matter (WM). Result: The density of PV-immunoreactive interneurons was significantly higher in patients with FCD type Ia compared to those with postmortem controls in all cortical layers and WM. There were significantly more PV-immunoreactive interneurons in FCD type Ia compared to TLE-HS in cortical layers 1 through 4 and WM. TLE-HS had significantly larger numbers of PV interneurons compared to post-mortem controls only in cortical layers 1 through 4. Conclusion: The increased number of PV positive, presumably inhibitory interneurons in FCD type Ia compared to TLE-HS and post-mortem controls may suggest a possible compensatory mechanism against ongoing seizure activity.
p511 EPILEPSY AND DEVELOPMENTAL OUTCOME IN INFANTS AND CHILDREN WITH STURGE-WEBER SYNDROME (SWS) S. E. Aylett*, and P. Rankin *Great Ormond Street Hospital NHS Trust and UCL Institute of Child Health, 3JH, UK; and UCL Institute of Child Health, 1EH, UK
Purpose: To define the severity of the epilepsy and cognitive outcome in infants and children with SWS. Method: Case notes review of Infants and children with SWS attending a specialist tertiary multidisciplinary clinic. Result: 50 children, with full data sets available for 45 were followed: age at review 2 months-17 years (mean 5 years, 9 months). 45 (90%) had developed epilepsy;21 (42%) had received regular aspirin prophylaxis. The pial angioma was unilateral in 38 (22 left, 16 right) and bilateral in 12. The Mean Developmental or Intellectual Quotient was 60 (Standard deviation 30). The age at epilepsy onset was birth to 12 years (mean 16 months, standard deviation 30 months). 30 (66%) had at least 1 episode of status epilepticus. Severe clusters of seizures occurred in 29 (64%). Seizures resulting in an acquired hemiplegia occurred in 17 (38% of the epilepsy population) 0.12 (27% of epilepsy population) proceeded to neurosurgical treatment of their epilepsy.10 (22% of epilepsy population) no longer had seizures 6 months prior to review and 3 (7%) were no longer on antiepileptic drug treatment at the time of review. Conclusion: Sturge-Weber syndrome is associated with the onset of epilepsy in the first 2 years of life and frequently associated with status epilepticus and an acquired hemiplegia. Infants and children have a variable developmental and cognitive outcome.
p510 LAYER SPECIFIC GENES EXPRESSION IN PATIENTS WITH FOCAL CORTICAL DYSPLASIA TYPE II L. Rossini*, R. Garbelli*, L. Tassi, M. Cossu, and R. Spreafico* *I.R.C.C.S. Foundation Neurological Institute, Milan, Italy; and Niguarda General Hospital, Milan, Italy
Purpose: Focal Cortical Dysplasia Type II are malformation of cortical development frequently associated with intractable epilepsy and characterized by cortical dyslamination and abnormal cell morphology (dysmorphic neurons and balloon cells). While balloon cells seem to arise from radial glial stem cells and show immature phenotype, dysmorphic neurons express markers indicative of origin from radially migrating pyramidal neurons and express markers of neuronal maturity. The pathogenesis of FCD and the origin of these cytological abnormalities, has not been clearly established. Aim of this work is to investigate the origin of these abnormalities by means of layer-specific genes expression in human surgical tissue presenting a neuropathological diagnosis of FCDII. Method: We performed RNA in situ hybridization (ISH) on 16 FCDII cases using a panel of cortical layer-specific markers, whose expression covers all cortical layers: Cux2, Ror-b, Er81, Nurr1 respectively expressed in layers II-III, IV, V and VI. Moreover, double ISH and immunocytochemistry using SMI and Vimentin antibodies were performed. Result: Layer specific genes expression pattern, inside lesion, reveals a complete disruption of laminar organization. Concerning cytological abnormalities, Cux2, Ror-b, Er81 and Nurr1 are expressed in both dysmorphic and balloon cells, with a high grade of variability for each analyzed case. Conclusion: The complete cortical re-distribution of the layer specific genes expressing neurons differ not only from a normal pattern but also from the less altered pattern typical of FCDI. The different expression of layer specific markers in dysmorphic and balloon cells might indicate their origin at different time windows during cortical development.
p512 FATAL POST-ICTAL VENTRICULAR FIBRILLATION IN A PATIENT WITH COMPLEX PARTIAL SEIZURES: A CASE REPORT L. Leung King's College Hospital, London, UK
Purpose: This case report describes a patient with a background of well controlled complex partial seizures who developed an episode of complex partial seizure whilst recovering from an uneventful, elective percutaneous coronary intervention (PCI). The patient subsequently had a post-ictal ventricular fibrillation cardiac arrest. The outcome given was SUDEP. This case and current evidence are discussed. There are no case reports on post ictal VF (ventricular fibrillation); this case is also one of SUDEP (sudden death in epilepsy) in a patient with well controlled epilepsy and post uneventful cardiac intervention, which is unusual. Method: Case presentation: An 80 year old Greek lady presented to our cardiology department for an elective PCI. She had a background of lifelong epilepsy- complex partial, well controlled with carbamazepine. Her last seizure was over 1 year ago. She was also Type 2 diabetic with known coronary artery disease- with 2 previous recent PCI procedures. The actual procedure was uneventful but she had an episode of complex partial seizure afterwards and soon after whilst in the post ictal phase developed fatal VF, which she did not survive. The coroner's verdict was one of SUDEP, with no evidence of procedure related cardiac arrest. Result: A negative bundle of investigations peri-event included: bedside echocardiograms, 12 lead ECGs and blood profile.
150 Abstracts
Conclusion: This is a case report that adds to the growing study of epilepsy and arrhythmias of which some can be fatal. This case of SUDEP in particular occurred in the context of post cardiac intervention and well controlled epilepsy. Result: 64 newborn babies of women with epilepsy were evaluated, the maternal age ranged between 15 and 38 years, only 11 (17%) mothers had taken folic acid before pregnancy, 34 were taking one AED, 19 two or more AED e 11 were drug free. The minority of them showed worsening in seizure frequency (23%). The deliveries were cesarean (48%), normal (44%), and forceps (8%). 31 children were male and 33 female. The rate of prematurity was 19%. The number of underweight children was 17%, and the number of malformations was 8/64. The most common malformations were: cardiac and minor malformations. In this study there was no difference between mono and polytherapy. Only three mothers had taken folic acid of these children with malformation. Conclusion: The frequency of children with malformations (12.5%) was higher than that described in the literature; however one explanation for this event could be the fact that pregnant women with refractory epilepsy were screened for our hospital, center of reference in epilepsy. In addition most pregnant women were not taking folic acid, which may also have contributed to the high number of malformed children.

p513 IMPACT OF PERI-ICTAL INTERVENTIONS ON RESPIRATORY IMPAIRMENT AND POST-ICTAL GENERALIZED EEG ATTENUATION M. Seyal, and L. M. Bateman University of California Davis, Sacramento, CA, USA
Purpose: Seizure-related respiratory dysfunction (RD) and duration of post-ictal generalized EEG suppression (PGES) may be important in the pathophysiology of sudden unexpected death in epilepsy (SUDEP). We assessed the impact of peri-ictal nursing interventions on RD and PGES duration in consecutive patients with localization-related epilepsy and secondarily generalized convulsions (GC) recorded during video-EEG telemetry. Method: Nursing interventions including administration of supplemental oxygen, oropharyngeal suction and patient repositioning were evaluated. Two-sided Wilcoxon signed-rank test was used to compare all GC with and those without intervention. Robust linear regression was used to assess the association between timing of intervention and duration of hypoxemia (SaO2 <90%) and PGES duration using data from only the first GC for each patient. Result: There were 39 patients with 105 GC. Oxygen desaturation duration data was available for 34 patients. PGES >2 seconds occurred following GC in 16 patients. There were 21 GC with no intervention and 84 GC with interventions. Seizure or convulsion duration was not significantly different between the two groups. PGES did not occur in the nointervention group. Desaturation duration was longer (p<0.0001), SaO2 nadir lower (p=0.0086) and end-tidal CO2 higher (p=0.0027) in the interventions group compared to no-intervention group. In the group with nursing interventions, earlier intervention was associated with shorter duration of oxygen desaturation (p<0.0001) and shorter duration of PGES (p=0.0012). Conclusion: Nursing interventions occurred in seizures with PGES and more severe RD. Earlier intervention was associated with reduced duration of RD and PGES. These findings should be considered when developing measures to reduce SUDEP risk.
p515 WOMEN'S EPILEPSY AND ANTIEPILEPTIC DRUGS SIDE EFFECTS ON REPRODUCTIVE HEALTH G. V. Odintsova*, N. Y. Koroleva*, A. A. Chugunova*, and L. A. Saukova *Institute of Human Brain of RAS, Saint Petersburg, Russian Federation; and Medical University, Saint Petersburg, Russian Federation
Purpose: To investigate the frequency of reproductive endocrine disorders (RED) for female epilepsy in association with the type of antiepileptic therapy (AEDs). Method: 155 women of reproductive age were enrolled in a prospective observational single-center uncontrolled comparative study of the AEDs side effects on reproductive health in 3 groups: 1gr.-monotherapy AEDs, 2gr. - polytherapy, 3g. no AEDs used. The diagnosis was established based on comprehensive exam, in accordance with ICD-10. Naranja Algorithm was used to determine reliability of communication AEDs RED. Result: 70 patients (45%) were in 1 gr, 65 (42%) in 2gr, 20 (13%) in 3 gr. The overall incidence of RED were 53%, 75% of them due to side effects of AEDs. Comorbid RED was observed in 21 (13%). In 61 (40%) cases RED were identified due to treatment of AEDs. 1 group - 40 patients were healthy (57%). In 21 (30%) - REN were associated with the taking AEDs. Comorbid RED was identified in 9 (13%). 2group - 19 patients (29%) didn't have a RED. Comorbid RED was observed in 9 patients (12%). RED associated with exposure to AEDs, was diagnosed in 38 patients (59%). 3group - 14 persons (70%) were healthy. Comorbid RED was diagnosed in 4 (20%). The 2 (10%) - retained menstrual irregularities arising from preceding AEDs. Differences in the frequency of RED in the comparison groups were statistically significant (p <0.001). Conclusion: The RED are a frequent side effect of AEDs therapy. Use of AEDs in females requires the monitoring of reproductive health.
p514 STUDY OF PREGNANT WOMEN WITH EPILEPSY IN BRAZIL: INITIAL RESULTS C. S. M. G. Miziara, V. A. G. Serrano, M. L. G. Manreza, S. D. L. Gis, and D. H. Nakanish Hospital das Clnicas of Medicine University os So Paulo, Sao Paulo, Brazil
Purpose: The effects of fetal exposure to antiepileptic drugs (AED) have been described frequently. However, in Brazil there are few studies about it. The aim of this study was to analyse over four years (2008 2011) the type of delivery and the condition of newborn babies. Method: This prospective and observational study was performed in the Clinical Hospital of So Paulo Medical School, Brazil
p516 OPTION GRID DECISION-SUPPORT INTERVENTION FOR WOMEN TAKING SODIUM VALPROATE AND PLANNING PREGNANCY P. Smith, R. Seal, and G. J. Elwyn University Hospital of Wales, Cardiff, UK
Purpose: Sodium valproate, normally recommended to treat genetic generalized epilepsies, is teratogenic and so not suitable for of child-bearing potential. Women already taking valproate should be involved in the
151 Abstracts
decision as to whether to change treatment. We have designed a decision support intervention, an option grid, to aid this process. Method: We identified relevant options and answers to frequentlyasked questions using the 2012 NICE guidelines, literature reviews and emailed consultations with experts in the field, so gaining maximum clinical consensus. Having developed an evidence document and drafted the option grid, we refined this further through consultation with local healthcare workers in the field of epilepsy. Result: We identified sodium valproate, levetiracetam and lamotrigine as the relevant treatment options. We chose five frequently-asked questions (FAQs), broadly addressing seizure control, teratogenicity, and adverse effects. We wrote answers to these FAQs in an Option Grid with an accompanying evidence document. Conclusion: The option grid and evidence document should help women, with their clinicians, decide their best treatment option. The first group consisted of 20 persons moderate TBI with convulsive syndrome, mean age 53.39 years, the second - 22 people with mild TBI with a convulsive syndrome, mean age 52.71 years. The groups were comparable in age, sex. Result: The study revealed that patients with mild TBI level of excitatory NAC (glutamic - 1145 0.24 mg, aspartic - 0228 0.05 mg) were significantly higher than in patients with moderate TBI with convulsive syndrome (0.805 0.07 mg and 0.164 0.02 mg, respectively), p<0.05. At the same time, there was a trend to an increase in brake NAC in patients with mild TBI with a convulsive syndrome compared with patients with moderate TBI with a convulsive syndrome (glycine - 1427 0.13 mg and 1345 0.19 mg respectively, proline - 1556 0.24 mg is the 1211 0.17 mg, respectively), p>0.05. Conclusion: Thus, patients with mild TBI with a convulsive syndrome marked by an imbalance of NAC: NAC increase in excitatory (glutamate, aspartate) and a tendency to increase the level of brake NAC (glycine, proline) compared with patients with mild TBI with convulsive syndrome.
p517 GLUTAMIC ACID DECARBOXYLASE ANTIBODY: A LINK FOR LOCALISATION RELATED EPILEPSY, STIFF-PERSON SYNDROME AND TYPE I DIABETES MELLITUS? REPORT OF TWO CASES G. Barcs*, A. Szucs, and A. Kamondi* *National Institute of Neurosciences, Budapest, Hungary; and Budapest, Hungary
Purpose: Antibodies to glutamic acid decarboxylase (GAD) are detected in about 80% of newly diagnosed type I diabetes mellitus (DM1) patients. High GAD antibody levels are present in up to 80% of patients with stiff-person syndrome (SPS). Epilepsy affects 10% of patients having SPS with GAD antibodies. We wanted to call attention to the possible GAD-related mechanism of epilepsy as well as to the GADlink of DM1, SPS, and epilepsy. Method: We present the history of two personal cases demonstrating the mechanism and link in question. Both had partial epilepsy, type I diabetes mellitus and stiff-person syndrome; and both had high serum GAD antibody levels. Result: In the several years history of both patients the three conditions had the same time sequence: firts partial epilepsy developed, it was followed in years by DM1, and finally SPS has appeared. In one patient plasma apheresis performed in a relatively initial period of SPS proved beneficial in that condition, improving the effect of pregabaline and benzodiazepine. Conclusion: Our cases support the observation that GAD antibody may be associated with partial epilepsy; not only with DM1 and SPS.
p519 EPILEPSY IN PRADER-WILLI SYNDROME; THE ISRAELI EXPERIENCE T. Gilboa, and V. Gross-Tsur Shaare Zedek Medical Center, Jerusalem, Israel
Purpose: Prader-Willi syndrome (PWS) is a rare neurogenetic systemic disorder (1:10,000 to 25,000 live births) characterized by severe cognitive, behavioral and physical disabilities. It is caused by a deletion (70%) in the paternally inherited chromosome 15q11-q13, maternal UPD (25%) in the same region or mutations in the imprinting center (IC, 5%) within that area. Recently, 1626% of PWS patients were reported to have seizures. Our goal was to assess the frequency and characteristics of epilepsy in the Israeli cohort of PWS patients. Method: After the approval of the institutional review board, information regarding epilepsy was obtained from 116 individuals with genetically confirmed PWS. A detailed questionnaire was completed following an interview with caregivers and medical chart review. Fifty-three subjects underwent EEG. Result: One hundred and sixteen questionnaires were completed (110 interviews, 116 charts reviewed). Sixteen patients had seizures, 7 (6%) epilepsy, 1 single seizure, and 8 (6.9%) febrile seizures only. There was a trend towards association between seizures, both non-febrile and febrile, and the deletion subtype (p=0.055). Fifty-three individuals, ages 4m-48y (mean 12.8y), underwent EEG. Patients with epileptogenic EEGs (9/53 patients, 6/9 deletions and 3/9 UDP) were relatively young (mean age 5.5y, p=0.02). Focal epileptic discharges were seen in 9/53 (ages 5m 13y, mean 5.5 years), with electrographic seizures recorded in 3/53. No patient had active epilepsy or received treatment. Conclusion: The prevalence of epilepsy in our cohort is low but EEG abnormalities approached 17% and electrographic seizures 5%. Routine EEG is advocated especially in the younger age group and in those with deletions.
p518 THE AIM OF WORK WAS TO STUDY THE CONTENT NEUROAMINOACIDS (NAC) IN WHEY OF BLOOD PATIENTS WITH TRAUMATIC BRAIN INJURY (TBI) WITH A CONVULSIVE SYNDROME I. I. Chernenko Kharkiv Medical Academy of Postgraduate Education, Kharkiv, Ukraine
Purpose: The aim of work was to study the content neuroaminoacids (NAC) in whey of blood patients with traumatic brain injury (TBI) with a convulsive syndrome. Method: We examined 42 patients with TBI at the age of 23 to 65 years. The level of NAC was determined in the first days after TBI received.
p520 CARDIAC ASYSTOLE WITH SYNCOPE AS A FIRST MANIFESTATION OF EPILEPSY A. Rakitin, M. Liik, and S. Haldre Tartu University Clinic, Tartu, Estonia
Purpose: Cardiac asystole provoked by epileptic seizures is a rare but important complication in epilepsy. Usually, ictal asystole occures in patients with long history of focal epilepsy and is observed principally in
152 Abstracts
left-sided epilepsies. The purpose of this report is to show that syncope caused by asystole could be the first manifestation of epilepsy. Method: A case report of 65-year-old, previously healthy female who was admitted in hospital for a transient loss of consciousness. Result: An electroencephalogramm (EEG) was performed. During the EEG, the patient had an ictal episode and a contemporary severe bradycardia leading to asystole. EEG showed an ictal pattern characterized by rhythmic 5Hz theta activity confined to the right frontal region. Five seconds after the beginning of the ictal episode the electrocardiogramm (ECG) showed a progressive bradycardia followed by complete sinus arrest that lasted 30 seconds. The asystole led to generalized slowness and was correlated with an extended EEG depression at the end of the ictal event. During this event, patient clinically had syncope with an apnoe and increase of facial muscle tone. Conclusion: Cardiac asystole may be the first manifestation of focal epilepsy. The right frontal lobe structures may play a role in autonomic regulation of cardiovascular responses. aim is to analyze the seizures and epilepsies in the elderly and report their treatment. Method: 51 patient aged 6083 years with epilepsy were analyzed clinically and with: laboratory analysis, EEG, evoked potentials, brain CT/ MRI, ultrasound of carotid and vertebral arteries, neuropsychological evaluation, consultation with internal medicine, neurosurgery and oncology specialists appropriately. Result: Provoked seizures were found in 7 patients and they were not treated as epilepsy. Cryptogenic focal epilepsies were found in 12 patients, most of them with vascular risk factors: diabetes mellitus, hypertension, hypercholesterolemia. Focal symptomatic epilepsies were found in 27 patients: 3 with post-traumatic epilepsy, 6 with cerebral degenerative changes, 9 with cerebral neoplasm, 6 primary and 3 metastatic and 9 post-stroke epilepsy. Idiopathic generalized epilepsies with seizures after the age of 60 years while on AEDs were found in 5 patients. Differential diagnostic possibilities in elderly patients with epilepsy made the diagnosis of epilepsy a challenge. Most of the patients were on AED treatment. AEDs were selected towards individual needs of each patient, considering the pharmacodinamics, pharmacokinetics of AEDs and patient's comorbidity. Surgery with additional AEDs was used for treatment of patients with operable brain neoplasm and ruptured cerebral aneurism. Conclusion: Awareness of increased incidence of epilepsy in the elderly, different clinical manifestations imitating other somatic/neurological conditions is a need for appropriate treatment of epilepsy in the elderly reducing their morbidity and mortality.
p521 QUALITY OF LIFE IN OLDER ADULTS WITH EPILEPSY A. Velez-Van-Meerbeke*, P. Quintero-Cuzquen, C. Alberto Galvis-Gomez*, and G. Guzman* *Universidad Del Rosario, Bogota, Colombia; and Hospital de la Samaritana, Bogota,
Purpose: To evaluate the quality of life in patients 65 years or older with active epilepsy in two hospitals in Bogot, Colombia. Method: The clinical charts including the electroencephalogram and diagnostic images of 120 patients were reviewed. Then the QOLIE-31 and version 10 of Minimental Tests were used to establish the patient's quality of life score and his cognitive level. Global quality of life and subscales scores were correlated with quantitative variables using the Spearman coefficient and differences between qualitative variables were evaluated with non-parametric tests. To establish the variables that explained the quality of life, we used an ordinal regression model. This study was approved by the Research Ethics Committee of both hospitals. Result: 106 patients of both sexes with an age of 71.96.32 years were studied. Epilepsy began at 61.9216.5 years and only 4% of patients were seizures free for the past two years. 88.7% had focal seizures and if an underlying etiology was identified, cerebral vascular disease was predominant. 71% were on Phenytoin monotherapy. Global quality of life score was 52.1715.83. It was affected by number of seizures, Mini-mental test score, educational level, socioeconomic status and MRI abnormalities. Other variables such as gender, housing site, job, type of seizures, availability of AED and treatment with phenytoin influenced QOLIE subscales. Conclusion: Quality of life is an individual perception that could be influenced by many factors. Patients over 65 years of age with epilepsy usually show a poor quality of life not only related to the disease but also to their socioeconomic conditions.

p523 OPTIMIZING PATIENT CARE AND MEDICAL EDUCATION THROUGH AAN EPILEPSY QUALITY MEASURES IN A UNIVERSITY HOSPITAL J. M. Cisneros-Franco*, M. A. Gutierrez-Herrera, J. B. Rodrguez-Castaeda*, J. M. Martnez-Valenciano*, L. L. Huerta-Esquivel, J. L. Gonzlez-Garza, and M. A. DazTorres *Universidad Autnoma de Nuevo Len, Monterrey, Mexico; and Hospital Universitario-UANL, Monterrey, Mexico
Purpose: The American Academy of Neurology & Physician Consortium for Performance Improvement (AAN/PCPI) suggested eight quality measures to be observed at every patient visit. Our aim is to compare the percentage of adherence to each measure before and after the implementation of a new worksheet in a referral center in north-eastern Mexico. Method: Interventional study including medical records filled by medical school seniors and junior residents supervised by an epileptologist. We included 104 consecutive people with epilepsy, evaluated before and after updating our clinic visit form, from November 2011 through midFebruary 2012. McNemar change test was used to compare the percentages of observance for AAN/PCPI standards i.e., seizure type and frequency, etiology, EEG, MRI/CT scan, AED side effects, surgical therapy referral, safety counseling, counseling for women with childbearing potential and physical exam. Each quality measure was considered to be fulfilled only if it was assessed and properly recorded. Result: Mean age was 34.7 (14.5), 52.9% women, epilepsy onset at age 19.8 (15.4), 78.1% presented with partial-onset seizures. All quality measures improved (previous vs new), reaching statistical significance for safety counseling 7.9vs55.4% and physical exam 60.6vs94% (p<0.01). The remaining increases were as follows: seizure type 84.8vs92.8%, frequency 50vs57.8%, etiology 69.7vs81.9%, EEG
p522 DIAGNOSING AND TREATMENT OF EPILEPSY IN THE ELDERLY G. A. Kiteva-Trencevska University Clinic of Neurology, Skopje, Macedonia
Purpose: Despite increasing incidence of new-onset epilepsy among elderly, there are reports of delay in their diagnosis and treatment. The
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62.7vs75.6%, brain imaging 44.1vs59.8%, adverse effects 10.8vs19.5%, childbearing counseling 16vs47.2%. Two patients were referred to presurgical evaluation. Conclusion: These preliminary results suggest that a quality-oriented epilepsy worksheet plays a role in improving the adherence to AAN/PCPI proposed standards, notably for safety counseling; thus enhancing medical education and, more importantly, our patients care. Conclusion: The spectrum of the electroclinical manifestations related to this entity may vary significantly and is not well defined yet. It is apparent that along with seizures a complex cognitive profile of disturbances is present. EEG findings are mainly encephalopathetic, and MRI images show a signal abnormalities in the limbic area. In contrast, the features in paediatric patients are more severe, in the context of status epilepticus and intractable seizures. Appropriate treatment results in varying degrees of clinical recovery.
p524 LONGTERM OUTCOME BEYOND 20 YEARS IN 66 PATIENTS WITH JUVENILE MYOCLONIC EPILEPSY P. Senf, B. Schmitz, M. Holtkamp, and D. Janz Vivantes Humboldt Klinikum, Berlin, Germany
Purpose: JME is the one of the most common IGE subsyndrome, but little is known about the long term outcome. The aim of this study was the analysis of the longterm outcome of a series of JME patients. Method: Out of 339 records of patients with IGE from the Janz-Archive of the Charit Department of Epileptology, 66 patients (10.2%) matched the inclusion criteria. Minimum follow-up time was 20 years, remission was defined by a minimum of five years seizure freedom. Result: We enrolled 66 patients with a mean current age of 62.4 years who had been followed up for a mean of 44.6 years. A total of 39 patients had become seizure free (60%), 45 years after diagnosis. Among seizure free patients 28 (43.1%) were still taking AED, and 11 were off medication (17.5%). From 27 patients without remission (40.9%), 11 (40.7%) reported, to have had seizure-free times > 5 years in the past. 16 (59.3%) showed a poor course with no seizure - free time longer than 5 years so far. 54 were still taking AED, 38 in Monotherapy (70.4%) and 16 in Polytherapy (29.6%). Absence seizures appeared significantly more often in the patient group without remission (p = 0.009). Conclusion: This study analyses the long term outcome of a well defined sample of patients with JME. Seizure remission occurred in 60% of patients, 17.5% remained seizure free without AED. Appearance of absence seizures was an attribut for a poor course with ongoing seizures without remission (p=0.009).
p526 FEATURE COMPARISON FOR REAL-TIME DETECTION OF NOCTURNAL SEIZURES USING ACCELEROMETRY C. Ungureanu*, M. Van Bussel*, I. Y. Tan, J. B. A. M. Arends, and R. M. Aarts *HOBO Heeze, VE, The Netherlands; Kempenhaeghe, Heeze, The Netherlands; and Eindhoven University of Technology, Eindhoven, The Netherlands
Purpose: It is important to monitor in real-time patients with convulsive epileptic seizures. Especially nocturnal seizures are at risk of going unnoticed. Method: Accelerometry among other techniques can provide an effective tool to accomplish the above goal. The small size of the accelerometer and new wireless based technologies are strong points towards developing portable devices to detect convulsive seizures. We studied the discriminating power of the mostly used features derived from accelerometry. Additionally we present a new method to determine the thresholds for classification derived from non-seizure movement patterns of the patient. Finally we evaluate the features and classification method on data recorded on 18 patients (> 60 seizures) having a broad spectrum of convulsive epileptic seizures. Result: We show that features derived from the amplitude of the signal have a lower discriminating power in comparison with the ones derived from the phase. Also, relatively simple computation efficient features corroborated with the classification method introduced by us provide good results. Conclusion: Our research points out that two accelerometer sensors represent a minimum requirement for the detection of nocturnal convulsive seizures.
p525 ELECTROCLINICAL FEATURES IN EPILEPSY CAUSED BY VOLTAGE GATED POTASSIUM CHANNEL ANTIBODIES N. Mullatti*, K. Kioulachidis, N. Moran*, S. Goyal, and M. Lim *Kings College Hospital, London, UK; King's College, London, UK; and Evelina Children's Hospital, London, UK
Purpose: VGKCA related epilepsy is a relatively new autoantibody syndrome presenting subacutely with seizures, cognitive impairment and variable neurological involvement. The electroclinical features of this entity are not well described, and our understanding of this condition still evolving. The aim of this paper is to describe the electroclinical features of the seizures with adult and pediatric presentation. Method: 12 patients (9 adults and 3 children) who were diagnosed with VGKCA related illness are presented. All patients underwent neurological evaluation, MRI scans, EEGs and VideoTelemetry, CSF, Autoantibody testing and Neuropsychology. The clinical course of the illness, the type of treatment, and the response to it were studied. Result: All adult patients presented with seizures, neuropsychiatric features with cognitive, memory, and behavioral problems. All patients had positive VGKC antibodies from low titres to high, and all showed clinical and neuropsychological improvement with treatment.
p527 ACUTE ENCEPHALITIS WITH REFRACTORY REPETITIVE PARTIAL SEIZURES (AERRPS): PRESENTATION OF THREE CHILDREN CASES V. I. Venegas*, M. Hernandez, and C. Alvarez *Clinica Alemana Santiago, Santiago de Chile, Chile; and Pontificia Universidad Catolica, Santiago de Chile, Chile
Purpose: AEERPS is a rare and catastrophic epileptic encephalopathy reported in 1986. Its etiology is still under study, immunological disorder is postulated due to the presence of autoantibody to glutamate receptor Glue2. This study presents 3 Chilean cases that meet defined clinical criterions (SAKUMA). Method: A retrospective report of three cases displaying these clinical criterions: prolonged acute phase, partial seizures with symptoms persisting from the acute to the convalescence phase, seizures frequently evolving into epileptic status, marked intractability of seizures, and exclusion of related disorders. All cases were studied using continuous and intermittent electroencephalography and several MRIs. The follow up period for clinical outcome was an average of 2 years. Result: Three cases, 2 females, 33 months and 8 years old, and a male, 36 months, with 5, 14, and 3 day fevers respectively. All had sudden
154 Abstracts
conscience impairment and generalized tonic clonic seizures evolving to a refractory convulsive state (CS). Treated with 11, 13, and 14 AED, IVGG, MPS. Normal MRIs at admission. EEG showed initial diffuse slow waves with focal or generalized spikes and burst-suppression pattern. Evolutions were refractory epilepsy, severe mental retardation, spastic quadriparesis, gastrostomy. Tracheostomy in both females. All had AcRc Glut epsilon 2 in CSF (+). Conclusion: AERRPS evolves to refractory epilepsy from the actue phase, therefore CS could be the first step in an epileptic encephalopathy. It could have an auto-immune etiology, related to Ac receptor Glue2 in CSF. The prognosis is poor. More studies are necessary to understand the physiopathology and establish effective treatment. Purpose: Infantile spasms (IS) are age-specific seizures commonly associated with an epileptic encephalopathy. The optimal evaluation and treatment of children with IS is not known. The aim of this survey was to assess the current approach to IS and to plan future multicenter clinical trials. Method: A survey was distributed electronically to members of the Child Neurology Society. Anonymous responses were collected over a two week period. Result: The response rate was 18.5% with 222 responses. Ninety-four percent of responders were from the United States. Seventy percent of responders reported seeing 10 or fewer new-onset cases of IS per year. The most commonly used first-line treatments for IS due to an unknown etiology were adrenocorticotropic hormone (ACTH) (67%), oral corticosteroids (15%), and vigabatrin (9%). The most commonly used firstline treatments for IS due to a structural/metabolic etiology (excluding tuberous sclerosis [TS]) were ACTH (44%), oral corticosteroids (23%), vigabatrin (14%), and topiramate (12%). Most responders (86%) use vigabatrin as the first-line treatment for IS due to TS. We found that the diagnostic evaluation of IS varied among clinicians. Conclusion: While ACTH is still the most commonly used first-line treatment for IS not due to TS, some clinicians use corticosteroids, vigabatrin, and topiramate as first-line treatments for this group. The evaluation and treatment of IS varied among responders. Infantile spasms are relatively uncommon, therefore future clinical trials will require multicenter collaboration. An important first step in such collaboration is the standardization of the evaluation and treatment practices within and between participating centers.
p528 AUTOIMMUNE MEDIATED SEIZURES WITH ENCEPHALOPATHY: A REVIEW OF CLINICAL AND ELECTROPHYSIOLOGICAL FEATURES Y. Hacohen*, S. Tang, Y. A. Hernandez Vega, S. Wright*, C. Hemingway, A. Clarke, E. Wassmer, A. Vincent*, and M. Lim *University of Oxford, John Radcliffe Hospital, Oxford, UK; Evelina Children's Hospital, London, UK; Great Ormond Street Hospital, London; St Georges Hospital, London; and Birmingham Childrens Hospital, Birmingham,
Purpose: To describe the seizure semiology and electrophysiological features of paediatric patients with presumed autoimmune epileptic encephalopathy. Method: Patients (n=40) presenting with a new onset seizure disorder and encephalopathy who were subsequently diagnosed with an autoimmune aetiology were identified from 5 tertiary paediatric neurology centres (20072010). Clinical and investigative data (including EEG) were retrospectively reviewed. Result: Generalised seizures (generalised tonic-clonic, atypical absence, atonic) were the most common (n=34), followed by focal dyscognitive seizures in 18 cases. Focal seizures were reported in 9, with epilepsia partialis continua seen in 2 cases. Seizures were resistant to first line therapy leading to intensive care support in 13 (32%). EEG was performed in 39 cases. Initial EEG was encephalopathic or showed a slow background in 35 (90%). Ten of these cases had asymmetrical slow wave activity. Of the remaining four, two (5%) demonstrated fast activity presumed secondary to drugs; one (3%) was normal; and one (3%) had focal epileptic discharges. Initial and/or subsequent EEGs where performed demonstrated epileptiform discharges in 11, which was multifocal in five and focal in six (temporal/parietal n=3, anterior n=1, posterior n=1). An auto-antibody was found in 45% of the patients (10 NMDAR, 7 VGKC and 1 with Glycine receptor antibodies). There were no statistical differences between the antibody positive and negative groups in the frequency and type of seizures witnessed. Conclusion: Autoimmune epileptic encephalopathies have a heterogeneous presentation with different type of seizures. Refractivity to antiepileptic treatment during the acute presentation appears to feature in this group of patients.
p530 REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION CAN BE ADJUNCTIVE METOD TO LOW ANTICONVULSANTS DOSES V. Kistsen, and V. Evstigneev BelMAGE, Minsk, Belarus
Purpose: The aim of our study is to assess the effectiveness of low-frequency repetitive transcranial magnetic stimulation (rTMS) as an adjunctive treatment for epilepsy patients. Method: Nineteen patients (mean age 35.42.9 years) who take subtherapeutic doses of anticonvulsants (AED) were studied. RTMS (1 Hz, 20% of big ring coil (Neurosoft) MMI intensity) was performed during ten consecutive days at the temporal lobe projection. Some of patients had prolonged rTMS course - two times per week during 2 monthes. The point of stimulation was selected by MRI and EEG data. The neuropsychological tests, QOLIE-31 and SSQ were performed for all patients. Result: Mean seizure frequency per week after 10 rTMS significantly decreased in the following 4-week after rTMS period compared with the pre-treatment period (4.12 vs. 0.75; P=0.023) which corresponds to 76% reduction and correlated with topiramat taking. Number of interictal epileptiform discharges decreased in 62.5% patients (P<0.05). There were increasing of alpha-rhythm amplitude and frequency in all patients. Amplitude, index, number and size of pathologic slow EEG-activity focuses were lowered in 80% cases (P<0.05) during 4 weeks period after rTMS. Improvement of neuropsychological tests, QOLIE-31 and SSQ results were revealed (P<0.05). Chronic rTMS supported condition of seizure frequency decreasing and positive EEG changes. Conclusion: 1 Hz low intensity rTMS has a significant antiepileptic effect in patients when combined with small doses of anticonvulsants what can to allow AEDs negative symptoms reduction. Additionally, our results indicate that rTMS can improve the psychological condition and quality of life of these patients.
p529 THE CURRENT TREATMENT OF INFANTILE SPASMS AMONG MEMBERS OF THE CHILD NEUROLOGY SOCIETY S. M. Joshi*, J. R. Mytinger, and P.E.R.C. Section On Infantile Spasms *University of Michigan, Ann Arbor, USA; University of Virginia, Charlottesville, VA, USA; and Ann Arbor, USA
155 Abstracts
p531 EFFECT OF PHYSICAL EXERCISE DURING ADOLESCENCE ON BEHAVIORAL CHANGES IN RATS SUBMITTED TO PILOCARPINE MODEL OF EPILEPSY IN IMMATURE BRAIN R. M. Arida*, F. G. Novaes*, S. Gomes Da Silva*, M. ToscanoSilva*, L. Peixinho-Pena*, F. Scorza, and E. Cavalheiro *Universidade Federal de So Paulo, So Paulo, Brazil; and UNIFESP, Sao Paulo, Brazil
Purpose: To investigate whether a physical exercise program undertaken during adolescence can influence behavioral changes of rats submitted to status epilepticus (SE) in early life using the pilocarpine model. Method: Male Wistar rats at 18 (P18) and 28 (P28) days old were divided into four groups: control, exercise, SE and SE exercise (n= 12 each group). SE was induced through the administration of pilocarpine (170 and 260 mg/kg, i.p., at P18 and P28 respectively). Animals from P18 were subject to the exercise program between P21 and P90 and animals from P28 between P31 and P90. Behavioral analysis to determine the number of seizures was performed from P45 to P90. Open Field and Morris Water Maze tests (between P55 and P62) were performed for both groups. Result: Only animals submitted to SE at P28 presented spontaneous recurrent seizures during the observational period. A significant reduction in seizure frequency was observed in comparing the SE exercise with the SE group. In the Water Maze test, lower latency to find the platform was detected in exercise group compared to control group (P18/P28). Nevertheless, no significant difference was observed among SE and control groups and SE and SE exercise groups (P18/P28). In the Open field test, a significant difference was observed in central locomotion between exercise and control groups and SE exercise and SE (P18/P28). Conclusion: Our findings indicate that physical exercise program during the adolescent period reduces seizure frequency and increases exploratory locomotion in rats submitted to pilocarpine model in early life. weekly with the standard setting. The settings are gradually increased in frequency and duration according to individual possibilities. Discussion: The preliminary results of this feasibility study show that WBV is tolerated by patients with epilepsy and ID. More detailed data on acceptance and tolerability will be accumulated during the 12 month-period of the study. Presumably, the group is too small and the follow-up too short to show statistic significant results on BMD.

p533 LOCAL SPECIALISTS KNOWLEDGE OF PLANTS WITHIN BARGUNA DISTRICT OF BANGLADESH: A SAFE ALTERNATIVE THERAPY FOR EPILEPSY IN PATIENTS WITH BRAIN INSUFFICIENCY M. A. H. Mollik Practical Academy on Wise Education and Research Foundation, Dhaka, Bangladesh
Purpose: Epilepsy is prevalent worldwide and is also present in both rural and urban areas of Bangladesh. Due to epidemiological transition the burden of this disorder is high. Patients along with their families and the whole society suffer from a range of physical, psychological, and socioeconomic problems. Allopathic medicines have no known remedy for cure of epilepsy but merely serve to control secondary symptoms. On the other hand local specialists claim to treat of epilepsy with plants resulting in complete cure. The studies were carried out in Barguna district of Bangladesh. Method: Interviews were conducted in the native dialect, and plant samples as pointed out by the local specialists in guided field-walks were collected, and identified at the Bangladesh National Herbarium. Local specialists administered treatment mainly by the concoctions, decoctions majorly through oral and dermal routes to treat of epilepsy. Result: The plant names obtained in the studies included Achyranthes aspera L., Aloe vera (L.) Burm.f., Bacopa monnieri (L.) Wettst., Cinnamomum camphora (L.) J.Presl, Cocos nucifera L., Datura metel L., Ficus benghalensis L., Lawsonia inermis L., Maranta arundinacea L., Nigella sativa L., Ocimum gratissimum L., Santalum album L., and Stephania japonica (Thunb.) Miers. Conclusion: Anti-epilepsy activities have been reported for a number of plants in the scientific literature for the plants used in Bangladesh for treatment of epilepsy. It is expected that the plants observed to be used for treatment of epilepsy by the local specialists can be subjected for further bio-activity studies, which studies can lead to discovery of better drugs.
p532 WHOLE VIBRATION THERAPY IN PERSONS WITH EPILEPSY AND ADDITIONAL HANDICAPS: A FEASIBILITY STUDY I. Smolenaers, F. Tan, and F. Schouwenaars Kempenhaeghe, Sterksel, The Netherlands
Purpose: This feasibility study follows from a previous study (K. Beerhorst, F. Tan - 2009) on the prevalence of low bone mineral density (BMD) in adult residents of a tertiary epilepsy center. 78% of the research population (patients with epilepsy and additional handicaps) had a low BMD: osteopenia (43%) or osteoporosis (35%). Pharmaceutical treatment was started by prescribing Bisphosphonates, vitamin D and/or Calcium. Because of the drawback of Bisphosphonates (no evidence how long treatment should continue, possibility of side effects, precautions when swallowing the drugs) we looked for alternative therapies to positively influence the BMD. Method: After reviewing the literature and consulting experts, Whole Body Vibration (WBV) Therapy emerged as a possible therapy. WBV has demonstrated modest effects in other populations. In collaboration with the manufacturer the standard WBV settings were determined. After each session of WBV training, a log and questionnaire is filled. Assessments are scheduled at fixed times. Result: Twenty patients met the inclusion criteria. All were diagnosed with epilepsy and an intellectual/physical disability. No patient withdrew after the try-out, and all started treatment in January 2012, three times
p534 SUCCESSFUL PLASMA EXCHANGE TREATMENT OF MULTIFOCAL MYOCLONUS. TWO CASE HISTORIES I. Gati*, O. Danielsson*, G. Leijon*, V. Szekeres, N. Dizdar*, H. Gauffin*, and M. Vrethem* *Linkping University, Linkping, Sweden; and Division of Neurology, Pcs, Hungary
Purpose: Four- and six-years follow up of two adult patients with acquired multifocal myoclonus are presented. Method: Detailed case histories and clinical data are presented.
156 Abstracts
Result: Myoclonic jerks in the head, upper extremities, and in the abdominal muscles were the dominating symptoms, together with excessive sweating. Emotional or physical stress and exertion of muscle contraction triggered the symptoms. Repeated electroencephalography (EEG) and electromyography (EMG) did not demonstrate central nervous system hyperactivity and peripheral muscle hyper excitability. Based on the clinical symptoms brain stem origin was assumed. Administration a several different antiepileptic drugs were ineffective. An autoimmune mechanism was postulated on the basis of a threshold increase of voltage-gated potassium channel antibodies. Monthly regular intravenous immunoglobulin treatment resulted in one month symptom-free periods, during two years follow up in one patient, while the immunoglobulin treatment had no effect in the other patient. Plasma exchange caused marked recovery, in both cases. One patient gained six months symptom-free periods, after 5 consecutive plasma exchanges, while the symptoms of the other patient were substantially decreased during a period of 4 - 5 months, after the treatment. None of the patients need antiepileptic therapy whilst on regular plasma exchanges. Conclusion: These case histories emphasise that immune-modulating treatment could be effective in central nervous system hyperactivity disorders, even if only weak laboratory data support the autoimmune mechanism. These treatments probably need to be aggressive, at least in the beginning and continous over time, as earlier suggested by Angela Vincent and her co-workers.
p536 THE KETOGENIC DIET IN CHILDREN WITH DRAVET SYNDROME - THE AUSTRIAN EXPERIENCE A. Dressler, M. Mrzinger, E. Reithofer, P. TrimmelSchwahofer, A. Mhlebner-Fahrngruber, G. Pahs, F. Benninger, R. Grassl, and M. Feucht Medical University Vienna, Vienna, Austria
Purpose: Dravet syndrome is a rare epilepsy syndrome in infancy with multiple seizure types, psychomotor slowing and unfavourable outcome. The ketogenic diet has proven some efficacy in Dravet syndrome, and has shown to be efficacious in other seizure disorders on prolonged generalised seizures and on fever induced status epilepticus. Our aim was to evaluate the efficacy and the safety of the ketogenic diet in patients with Dravet syndrome. Method: We analysed retrospectively data of all children with a clinical and genetically verified diagnosis of Dravet syndrome at the Medical University of Vienna who were started on the ketogenic diet between 1999 and 2012. Result: We report on 8 children, 4 (50%) were responders. 1 child became seizure free, but relapsed because of incompliance adhering to the diet. One responder relapsed after 3 months on the diet, whereas the other two responders (25%) are still on the diet with a persistent seizure reduction. Conclusion: We observed a good initial response on the KD, but moderate long-term efficacy, probably due to the natural course of Dravet syndrome. In contrast, 2 patients remained free from seizures under Stiripentole. However, the KD prevented prolonged seizures and status epilepticus, and no side effects with a need to interrupt the diet in responders were observed.
p535 WORSENING OF SEIZURES FOLLOWING ABRUPT DISCONTINUATION OF MARIJUANA IN AN EPILEPSY MONITORING UNIT A. Kabir*, M. Hegde, C. Santos-Sanchez, C. Hess, and P. Garcia *San Francisco VA Medical Center, San Francisco, CA, USA; and University of California San Francisco, San Francisco, CA, USA
Purpose: Cannabinoids such as marijuana have been described to have anticonvulsant properties. These findings however remain controversial. Two reports described a reduction in seizure frequency after marijuana use (Consroe 1975, Ellison 1990), while another suggested sporadic marijuana caused seizures to recur after remission (Keeler 1967). Two double-blinded placebo-controlled studies used cannabidiol (CBD), the primary non-psychoactive compound of cannabis, as an adjunct to anticonvulsants. Cunha et al (1980) demonstrated a beneficial effect in 7 of 8 patients; while Ames and Cridland (1986) showed no significant change in seizure frequency for 12 patients. Here, we describe two additional well substantiated patients, who demonstrated significant benefit from chronic marijuana use. Method: We reviewed our experience at UCSF and the SFVAMC with patients undergoing continuous vEEG monitoring, who demonstrated increased seizures in the setting of abrupt cannabis discontinuation. Result: Following discontinuation of marijuana, while continuing their outpatient medication regimen, two patients suffered dramatic increases in seizure frequency, suggesting that outpatient marijuana usage had contributed substantially to seizure control. Conclusion: We present two cases of patients who derived benefit in seizure control from marijuana, demonstrated by worsening seizures in the setting of abrupt marijuana withdrawal. These cases therefore suggest that, for at least a subset of patients with focal epilepsy, marijuana use may provide an anticonvulsant effect. Alternatively, our cases may represent cannabis withdrawal, however this is unlikely given the lack of other withdrawal symptoms. We believe that these cases support further research into the potential benefits of medicinal marijuana for patients with epilepsy.
p537 CESSATION OF REFRACTORY CONVULSIVE STATUS EPILEPTICUS AFTER IMPLANTATION OF VAGUS NERVE STIMULATION (VNS) THERAPY A. Soto, G. Contreras, V. Sainz, and H. Scholtz Centro Medico Docente La Trinidad, Caracas, Venezuela
Purpose: To report a 4 year-old patient who showed cessation of refractory convulsive status epilepticus (SE) after VNS implantation Method: This patient had a previous history of perinatal asphyxia, hypoxic isquemic encephalopathy and seizures since the neonatal period. She was put on Phenitoyne (PHT) and Phenobarbital (PB). By the first month of age, she had recurrent seizures appearing during sleep, opened the eyes, stared with a tonic flexion of head. In November 2008 after a Rotavirus Infection she had status epilepticus receiving diazepam and midazolam. In January 2009, infantile spasms were observed with a typical hypsarritmia pattern in the EEG. She also had focal and GTC seizures. She was admitted in the PICU receiving Pentothal and midazolam and received ACTH, LTG, TPM, Levetiracetam (LEV), CZP and a Ketogenic Diet. In December 2009 she developed status epilepticus receiving midazolam and Pentothal. Psychomotor deterioration was noted also. In March 2010 she had another status epilepticus and remained in a barbituric coma for 20 days receiving Levetiracetam, Lacosamide, Vigabatrin and Clonazepan. She was implanted with VNS Therapy after the last episode of refractory SE. Initial settings: OC 1.0 mA, frequency 30 Hz, PW 500ls, on time 30 sec, off time 5 min. Result: After VNS Therapy the patient had 100% reduction of convulsive seizures. She has had 4 focal seizures not requiring admission to PICU. Her mental status has dramatically improved. Conclusion: VNS Therapy may be a valid alternative for the treatment of refractory convulsive SE in a specific group of patients.
157 Abstracts
p538 ELECTROLYTE HYDRATION THERAPY IN CONTROL OF SPIKE AND WAVE DISCHARGES IN THE WAG/RIJ RAT MODEL OF ABSENCE EPILEPSY D. Isaev, A. Talnov, A. Savotchenko, and G. Holmes Bogomoletz Institute of Physiology, Kyiv, Ukraine
Purpose: We hypothesized that hyperosmolarity may be responsible for the antiseizure effect of electrolyte solution. In the present study, using a classical animal model of absence epilepsy we attempted to extract the antiseizure effect of rice-based oral electrolyte solution due to hyperosmolarity from other possible effect of this electrolyte solution. Method: Each rat was implanted with recording electrodes for the subsequent EEG recordings. At the day of surgery rats were anesthetized with a mixture of ketamine/xylazine (80/8 mg/kg) intramuscularly. For recording animals were placed in a special chamber and spontaneous field potentials were recorded using multi-channel extracellular amplifier. The electrolyte solution contained: sodium chloride of 3.4 g/L, potassium chloride 1.3 g/L, trisodium citrate, 2.9 g/l; ricecarbohydrate 40g/L; which provide per liter sodium 90 mEq, potassium 20 mEq, and a 270 mOsm. Spike and wave discharges (SWD) were counted manually by an investigator blinded to treatment group for per blocks of one hour. Result: Analysis of EEG recordings showed a gradual decrease of number of SWD per hour during the time of electrolyte solution consumption (33.02.9% of control level, p < 0.01). There were no changes in peak frequency (7.20.4 Hz) and duration (6.41.5s) of SWD compare to control recordings. Conclusion: The present study shows that using electrolyte base therapy can be effective as add on therapy to treat absence epilepsy. Treatment of refractory absence seizures with rice-based formulas may provide a cost effective, efficacious treatment of absence seizures. Whether such dietary treatment will carry over to other seizure types remains unclear. Conclusion: Automatisms in both TL and FL seizures have a different and specific order of appearance and laterality. A distinctive and strongly contralateral rhythmical rounded proximal automatism was identified in TLS
p540 EFFECTIVENESS OF THE USE OF AN OMEGA 3/6 COMBINATION IN PAEDIATRIC PATIENTS WITH REFRACTORY EPILEPSY E. J. Barragn Prez*, R. Huerta Albarran, and I. Heredia Barragn* *Hospital Infantil de Mxico Federico Gmez, Mxico, DF, Mexico; and Hospitasl General de Mxico, Mexico City, Mexico
Purpose: To compare efficacy and safety in the treatment of refractary epilepsy with a supplement combining EPA, DHA (omega 3 fatty acids) and GLA (Omega 6). Method: We review patients from the neurology department of the Childrens Hospital of Mexico who have refractory epilepsy, evaluating clinical characteristics of seizures, number of seizures and antiepileptic drigs (AED) 792 mg of EPA, DHA and GLA were administred for four weeks in order to assess the frequency of seizures as well as tolerbility and probable side effects. Result: The studywas condcuted with a total of 19 patients with follow up four weeks after the start of supplementation. we obtain a satisfactory clinical response with >80% decrease in daily number of seizures in more than 60% of patients. The mean number of seizures over all patients was reduced significantly from 2661 */- 37.5 to 5.92 3.48. In addition, a significant improvement in the neurocognitive capacity was observed in all patients. Conclusion: The co-adjuvant supplementation with high doses of EPA/ DHA/GLA may result in a reduction of the number of seizures in refractary epilepsy having in addition significant impact on neurocognitive aspects. To enhance the quality of life for paediatric patients with epilepsy supplementarion with a specific combination of these omegas should be reconsidered.
p539 TEMPORAL VERSUS FRONTAL LOBE SEIZURES WITH AUTOMATISMS IN CHILDREN WITH SURGICALLY VERIFIED EPILEPTOGENIC ZONE O. Grinenko Kazaryan Clinic of Epileptology and Neurology, Moscow, Russian Federation
Purpose: To compare semiology of seizures with automatisms originating from the frontal lobe (FLS) and from the temporal lobe (TLS) in children who became seizure-free after surgery. Method: We analyzed 25 videotaped TLS from ten patients and 16 videotaped FLS from six patients aged 3.516 years (mean 7.9 years). Median follow-up was 18 months (range 540 months). Fourteen types of symptoms and signs were evaluated in every seizure. The course of each seizure conditionally was divided in three consecutive stages. The time of symptoms onset was determined in relation to each stage of seizure. Result: Ipsilateral distal hand automatisms with contralateral arm distonic posture were seen only in the TLS (13 seizures in 5 patients), whereas proximal automatisms were more frequent in the FLS (14 seizures in 5 patients), then in TLS (5 seizures in 2 patients) (P <0.001). Ipsilateral manipulating distal automatism were more common in the TLS (P <0.007) (15 seizures in 7 patients) as bimanual manipulating distal automatism - in the FLS (9 seizures in 3 patients) (P <0.004). Nonmanipulating rounded rhythmical proximal automatisms in TLS were determined exclusively contralaterally and only during the first third of the seizure (5 seizures in 2 patients). Oral automatisms in FLS were seen only in the last third of the seizure (6 seizures in 2 patients).
p541 EFFECTS OF VAGUS NERVE STIMULATION ON SEIZURES AND CARDIOVASCULAR RESPONSES IN PATIENTS WITH DRUG-RESISTANT EPILEPSY I. Naldi*, B. Mostacci, M. Broli*, P. Guaraldi*, L. Alvisi*, G. Barletta*, F. Pittau*, C. Leta*, F. Bisulli*, P. Cortelli*, and P. Tinuper* *IRCCS Istituto delle Scienze Neurologiche, Bologna, Italy; and IRCCS Istituto delle Scienze Neurologiche di Bologna, Universit di Bologna, Bologna, Italy
Purpose: We aimed to describe the impact of vagus nerve stimulation (VNS) on seizure frequency and cardiovascular responses in refractory epilepsy patients. Method: Among refractory epilepsy patients who underwent implantation of VNS, from February 2007 to November 2011, we selected cases with a follow-up at least of one year. Neurological examination, brain magnetic resonance imaging, video-polygraphic recording including EEG and EKG, cardiologic examination, echocardiography, Holter EKG and ambulatory polysomnography were performed in all patients before VNS implantation. All patients underwent Head-up Tilt Test (HUTT), Valsalva Maneuver (VM), Hand-Grip (HG), Deep Breathing (DB) and Cold-Face (CF) before and after implantation.
158 Abstracts
Result: Ten patients were included, mean age was 41.9 years (range 28 55), mean disease duration was 32.9 years (range 2055). All patients had refractory focal seizures with or without secondary generalization. Seizure frequency improved from 30% to 90% in 6 patients, did not change in 3 patients, worsened in 1 patient and the VNS had to be turned off. There was no significant change in HUTT, VM or DB after VNS. The increase in Systolic blood pressure during CF and HG was significantly higher post VNS (respectively n=8, p=0.042; n=7, p=0.032 compared to pre VNS implantation. Conclusion: Seizure frequency improved in 6 out of 10 patients with VNS therapy. Our results show that VNS does not impair autonomic cardiovascular regulation, but increase sympathetic vasoconstrictor responses to pressor stimuli. Purpose: Can we improve seizure control and optimize individual treatment protocols in patients with Dravet-S using electronic documentation? What are useful anticonvulsant (ACD) combinations? Is Stiripentol (STP) combined with Clobazame (CLB) clinically useful. Method: 14 patients with Dravet syndrome aged 328 (median 11.5) years have been continuously seen in our epilepsy centre since 2007. The electronically documented clinical course in EpiVista was used to optimize the anticonvulsant (ACD) combinations in each patient. Pharmacoresistant patients received STP+CLB after 311 (median 8) ACD, and we compared the seizures during 2 months baseline (BL) before STP introduction with the 2 months observational period (STP maintenance dose, > 0.1 mg/kg CLB). Result: 4/14 patients became seizure free with VPA+TPM (n=3) or VPA+TPM+Br- (n=1). There was one dropout (loss of follow up). The remaining 9 patients recieved STP (1229 mg/kg, median 19) + CLB (0.100.16 mg/kg median 0.12). Seizure reduction > 50% occurred in 5/9 patients and one additional patient had been free of seizures since 9 months at the last visit with VPA+TPM+STP+CLB. Conclusion: Electronically augmented titration of ACD provides good seizure outcome in Dravet-S. The combination of STP+CLB is helpful in pharmacoresistant DravetS.
p542 HAS TRANSCRANIAL DC STIMULATION PROLONGED AFTER EFFECTS ON ABSENCES? M. Zobeiri*, A. Luttjohann, and G. Van Luijtelaar *Donders Institute for Brain Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, The Netherlands; and Radboud University Nijmegen, Nijmegen, The Netherlands
Purpose: Transcranial direct current stimulation (tDCS) is a putative novel non invasive therapy which might be beneficial in cortical epilepsies. It is widely accepted that the for absence epilepsy typical SWDs have a cortical origin. Here it is investigated whether anodal and cathodal tDCS affects local cortical excitability in a genetic rodent model of absence epilepsy and whether the effects persisted the next day. Method: Ten male WAG/Rij rats, minimally six months of age were used. Two stimulation electrodes were cemented on the cranium above the focal regions bilaterally, EEG electrodes were epidurally implanted. Rats received 4 series of 15 minute cathodal and anodal stimulation of 100 lA with an interval of 1h45 in a counter-balanced order while EEG was recorded. In a second experiment (n=4) the cumulative effects of cathodal stimulation with the same intensity and duration at 4 different time points were examined and compared with baseline and post stimulation day. Result: Cathodal tDCS decreased the number and total duration of SWDs in comparison with anodal stimulation, but only during and after the first 15 min of stimulation (Exp 1). The effects of cumulative cathodal tDCS (Exp 2) tended to increase (F= 3.14, p=0.06) over time. Rats had less SWDs in the post stimulation day compared to base-line. Histological evaluation showed no abnormalities in the stimulated regions. Conclusion: The preliminary outcome shows that cathodal tDCS can be considered as an effective method to reduce SWDs in this genetic absence model and that its effects may outlast the actual stimulation period.
p544 REFRACTORY EPILEPTIC ENCEPHALOPATHY RELATED TO MYCOPLASMA PNEUMONIAE INFECTION R. Buenache*, P. Morillo, M. A. Meseguer*, C. Perez Caballero, P. Quintana*, and G. Lorenzo *Hospital Ramon y Cajal., Madrid, Spain; Ramon y Cajal University Hospital, Madrid, Spain; Ramn y Cajal Hospital, Madrid, Spain; and Paediatric Neurology, Ramon y Cajal University Hospital, Madrid, Spain
Purpose: To report a case of a girl with febrile infectionrelated epilepsy syndrome (FIRES) after Mycoplasma infection, and successful response to sequential plasmapheresis. Method: We report the case of a previously healthy 4-year-old girl who initially presented decreased level of consciousness, fever up to 39C and recurrent partial and generalized seizures. Blood tests and CSF were normal. Slow background EEG activity. She was diagnosed with encephalitis. Broad-spectrum antibiotics and acyclovir were initiated. Result: All microbiological research including serologies, PCRs and cultures to search for neurotropic agents resulted negative, except for Mycoplasma pneumoniae seroconversion. During her evolution she developed refractory and recurrent clinical and electrical status epilepticus without response to valproate, phenytoin, levetiracetam, midazolam, propofol and thiopental. The neurometabolic study (blood, urine and CSF) was normal. Antineuronal antibodies and other autoimmune studies were negative. Normal brain MRI. EEG showed slow spike and wave discharges in both hemispheres. Immunology of CSF: initial elevated IgM and IgG in CSF. After high-dose steroids treatment, decreased Ig CSF levels, with later persistence of high levels; therefore she was treated with immunoglobulin and several multiple sessions of plasmapheresis. Afterwards, she recovered with a residual seizure disorder and autism-like behaviour. Control brain MRI showed cortical atrophy. Two months later, she remains without seizures, treated with clobazam, ethosuximide, valproate and zonisamide. Conclusion: Our case supports the hypothesis that Mycoplasma infection may trigger a FIRES. Furthermore, an adequate immunomodulatory therapy should be effective when an immunological disorder is observed.

p543 OPTIMIZED INDIVIDUAL TREATMENT PROTOCOLS IN PATIENTS WITH DRAVET-SYNDROME USING ELECTRONIC DOCUMENTATION WITH EPIVISTA R. Boor*, C. Dreiwes*, and U. Stephani *Northern German Epilepsy Centre, Schwentinental, Germany; and University Medical Center Schleswig-Holstein, Kiel, Germany
159 Abstracts
p545 DESCRIPTION OF CLINICAL CASE OF FEBRILE INFECTION-RELATED EPILEPSY SYNDROME (FIRES) S. N. Sivkova*, E. I. Bogdanov, F. M. Zaykova*, and E. A. Morozova* *Children Municipal Hospital, No. 8, Kazan, Russian Federation; and Kazan State Medical University, Kazan, Russian Federation
Purpose: Febrile infection-related epilepsy syndrome (FIRES) is a severe condition occurring mainly in children, with acute onset of status epilepticus during a febrile illness and subsequent refractory epilepsy in patient with previous normal development. Sometimes it causes difficultes for diagnostic at the onset. Methods: We prospectively identified FIRES in 7-year-old boy, who has refractory symptomatical focal epilepsy and progressive cognitive and behavioral disturbances, despite antiepileptic treatment. Results: 7-year-old boy had febrile respiratory infection for 6 days. At 7 day acute symptoms had appeared: psychiatric and cognitive problems (agitation, acute memory and disorientation, psychosis, speech and psychomotor arrest); neurological left hemiparesis, meningeal signs. Focal automotor seizures with secondary generalization had been started about 2025 times a day. All laboratory analyses (blood, cerebrospinal fluid), virul test, immunological test and MRI were normal. EEG showed multiregional epileptiform activity. The boy was treated like an atipical viral meningoencephalitis, but it was unsuccessful. Only using prednisolon 30 mg/day with gradual reduction of a doze and some combinations of antiepileptic drugs (oxcarbamazepine 38 mg/kg/day, valproic acid 45 mg/ kg/day, topiramate 7.5 mg/kg/day) have decreased frequency of seizures. One year later patient continued to present clusters of focal seizures and progressive cognitive regression. Conclusion: This description has shown that we always should keep in mind the possibility of development of severe epileptic encephalopathy in children after febrile infection with frequent seizures. in the acute phase and 8 developed drug resistant epilepsies (61.5%). Eight children had severe cognitive disturbance (61.5%). Only 2 children recovered without significant sequelae, both of them received IVIG in acute phase. Conclusion: This is the largest clinical series of FIRES from India. Treatment outcome remains poor despite using multiple AEDs, immunotherapy and barbiturate anesthesia. Immunotherapy with IVIG during early phase of the illness may have a favorable outcome.
p547 CONCORDANCE BETWEEN HISTORY AND EPILEPSY MONITORING UNIT EVALUATION FOR DIAGNOSING SEIZURES E. Khalid, S. Sinha, and K. A. Siddiqui National Neurosciences Institute, King Fahad Medical City, Riyadh, Saudi Arabia
Purpose: History and examination (H&E) are of a paramount importance in the diagnosis of epilepsy. Accurate history can help select patients who require comprehensive Epilepsy Monitoring Unit (EMU) evaluations i.e: long term EEG monitoring, dedicated structural and functional neuroimaging and neuropsychological evaluation. A detailed history could help us delineate seizure subtype and may obviate the need for comprehensive evaluation, and be cost effective. We compared epilepsy diagnosis made in outpatients using historical information to comprehensive EMU evaluation. Method: We reviewed seizure/spell diagnosis on consecutive patients made on basis of H&E and compared to the final diagnosis following comprehensive EMU evaluation. We also looked at their demographics and mean duration of epilepsy. Result: Ninety Six patients (Male-51, Female-45) with mean (+ SD) age 24 (+10.1) years and duration of epilepsy 11 (+9.7) years were recruited. Following outpatient evaluation probable diagnosis of focal seizure was made in 37, generalised in 29, Paroxysmal Non Epileptiform Seizures (PNES) in 6, and evaluation was inconclusive for seizure type in 24 patients. Following EMU evaluation diagnosis of focal epilepsy was made in 61, generalized epilepsy in 26, and PNES in 10 patients. Outpatient diagnosis was concordant to comprehensive EMU evaluation in 44.8% (43/96), which was 44.3% (27/61) for focal seizure, 42.3% (11/ 26) for generalised and 50% (5/10) for PNES. Conclusion: Concordance was seen in less then half of the patients recruited and was similar for all seizure subtypes. This study highlights deficiency of accurate history probably related to language barrier and or lack of health and educational literacy and signifies the importance of EMU evaluation in our population.
p546 CLINICAL PROFILE AND TREATMENT OUTCOME IN FEBRILE INFECTIONRELATED EPILEPSY SYNDROME (FIRES) IN SOUTH INDIAN CHILDREN V. Kollencheri Puthenveettil, S. Patil, A. G. Roy, D. Dhami, C. Nidheesh, and A. Kumar Amrita Institute of Medical Sciences, Cochin, India
Purpose: To describe clinical features and outcome of febrile infection related epilepsy syndrome (FIRES) in South Indian children. Method: Previously normal children aged between 2 to 12 years admitted with a prolonged status epilepticus or encephalopathy with recurrent seizures following a non-specific febrile illness between January 2009 and July 2011 were included. Result: A total 17 children were identified. 4 children were excluded before final analysis. Age ranged between 212 years (median 6 year 3 month). Seizure onset was 114 days (median 5 days) after the fever. Nonspecific respiratory infection was recorded in 10 children. Ten patients had status epilepticus at presentation. Four had recurrent seizures with encephalopathy. Cerebrospinal fluid studies were normal in all. Interictal EEG showed generalized slowing in all children. Focal epileptiform abnormalities were seen in 9. Neuroimaging was normal in 10 children (9 MRI, 1 CT). Treatment included multiple antiepileptic drugs (47 AED; median 5 drugs). Barbiturate coma was used in 6 for 2 to 10 days (median 2 days). Steroids were used in 10 (76.92%) children and IVIG in 4 (30.76%). Two children died
p548 SECONDARILY GENERALIZED SEIZURES IN TEMPORAL LOBE EPILEPSY B. Bn*, A. Fogarasi, R. Schulz, C. Gyimesi*, Z. Kalmr*, N. Kovcs*, A. Ebner, and J. Janszky* *University of Pcs, Pcs, Hungary; Bethesda Children's Hospital, Budapest, Hungary; and Epilepsiezentrum Bethel, Bielefeld, Germany
Purpose: Secondarily generalized tonic-clonic seizure (SGTCS) may rarely occur in temporal lobe epilepsy (TLE), but SGTCS is the major risk factor for sudden death and for seizure-related fatal injuries. Our aim was to investigate clinical factors associated with the occurrence of SGTCS in TLE by addressing two questions: (i) What clinical features
160 Abstracts
differentiate TLE patients who regularly had SGTCS from those who did not? (ii) Is there an association of secondarily generalized seizures with preceding seizure elements and clinical data. Method: We included 171 TLE patients (mean age: 34.410) who participated in our presurgical evaluation program, which included continuous video-EEG and MRI. Patients had a temporal lobectomy as a result of mesial or neocortical TLE. To re-evaluate the archived seizures, we selected the consecutively recorded seizures of each patient. If the patient had more than three recorded seizures, then we re-evaluated only the first three ones. Altogether 402 patients videorecorded seizures were re-analyzed. Result: A positive association between the presence of hippocampal sclerosis on the MRI and SGTCS in the patient history was found, while ictal speech and pedal automatism showed a negative association with a SGTCS history. The age of patients showed a positive, while patient's reactivity before and during the seizure, oral/pedal automatisms, and vocalizations showed a negative association with secondary generalization of a focal-onset seizure during video-EEG monitoring. Conclusion: Clinical features associated with SGTCS may help clinicians during presurgical monitoring indentify high-risk patients for SGTCS. Our study may help in understanding the pathophysiology of secondary generalization.
p550 IS THERE CLINICAL EVIDENCE FOR DIFFERENCES RELATED TO THE NEW CLASSIFICATION OF TEMPORAL LOBE CORTICAL DYSPLASIA? S. Fauser*, C. Essang*, D. Altenmller*, A. M. Staack, K. Strobl, B. J. Steinhoff, T. Bast, S. Schubert-Bast, M. Prinz*, J. Zentner*, and A. Schulze-Bonhage* *Freiburg, Germany; Kork, Germany; and Heidelberg, Germany
Purpose: The new ILAE classification for focal cortical dysplasia differentiates between isolated FCD (FCD type 1) and with an associated hippocampal sclerosis (FCD type 3a). The rational for this differentiation was a presumed different clinical course. Method: 50 patients with temporal FCD type 3a and 31 patients with temporal FCD type 1 were included. Both patient groups were compared to 18 patients with temporal FCD type 2. Result: Patients with FCD type 1 and type 3a presented with similar clinical features. No differences were found with respect to age at epilepsy onset, age at epilepsy surgery, and the occurrence of an aura (mainly epigastric). A normal appearing lateral temporal lobe was seen in 12% of patients with FCD type 1 and in 27% of patients with FCD type 3 (p= 0.09). The postoperative outcome was nearly identical with 5060% of patients completely seizure-free. Only febrile seizures were significantly more frequently reported in patients with FCD type 3a (p=0.03). FCD type 2, however, was clinically different with respect to the occurrence and the type of auras [significantly less common in FCD type 2 (p=0.02) and more polymorphic]. Conclusion: Patients with FCD type 1 and type 3a present with clinically similar features, probably because of involvement of similar networks into epileptogenesis. Based on these findings a splitting of temporal FCD into FCD type 1 and type 3a founded on different clinical phenotypes is challengeable. FCD type 2, however, presents with some peculiarities which have not been considered in the ILAE classification so far.
p549 THE SPECTRUM OF FRONTAL SEIZURES: ANATOMO-ELECTRO-CLINICAL CORRELATIONS USING SEEG A. Mcgonigal, F. Bonini, A. Trbuchon-Da Fonseca, F. Bartolomei, M. Gavaret, and P. Chauvel Service de Neurophysiologie Clinique & Institut de Neurosciences des Systmes-INSERM UMR 1106, Marseille, France
Purpose: To study whether patients with frontal lobe epilepsy may be categorised semiologically and whether certain semiological patterns are associated with different sublobar seizure organisation. Method: We studied anatomo-clinico-electrical correlations in 54 patients with frontal lobe seizures, explored with stereoelectroencephalography (SEEG). Semiological features and SEEG data were identified and categorised in a semi-quantitative way. Hierarchical cluster analysis was used to compare patients. Result: Three main groups were characterised by a significant degree of shared semiological features between patients. These showed distinct electro-anatomical seizure organisation along caudo-rostral, mesio-lateral and dorso-ventral axes. Group 1 was characterised by elementary motor signs (e.g. tonic posturing, head version, clonic jerks) without more complex gestural motor behaviour, involving precentral and/or premotor structures. Group 2 was characterised by both specific elementary motor signs and gestural motor behaviour with a non-naturalistic (nonintegrated) appearance, involving both premotor and prefrontal structures. Group 3 showed naturalistic (integrated) gestural motor behaviour without elementary motor signs, arising from prefrontal structures. Emotional features were associated with mesial prefrontal involvement. Stereotyped movements were associated with dorsolateral prefrontal cortex involvement. Conclusion: Categorisation of frontal seizures is possible according to semiological features, corresponding to different electro-anatomical organisation along rostro-caudal, mesio-lateral and dorsoventral axes. Electroclinical reproducibility of seizures, within an anatomo-functional framework, suggests an important role for cortico-subcortical circuits in seizure organisation.
p551 EPILEPSY AND SPEECH-RELATED PROTEIN SRPX2 CONTROLS NEURONAL MIGRATION IN THE DEVELOPING RAT BRAIN CORTEX M. Salmi*, N. Bruneau*, J. Cillario*, N. Lozovaya*, E. Buhler*, F. Watrin*, A. Massacrier*, T. Tsintsadze*, V. Tsintsadze*, C. Zimmer, R. Cloarec*, C. Cardoso*, C. Villard, F. Muscatelli*, P. Durbec, V. Pauly, I. Khalilov*, Y. Ben Ari*, N. Burnashev*, A. Represa*, and P. Szepetowski* *INSERM U901 - INMED, Marseille, France; CNRS UMR6216, Marseille, France; INSERM U911, Marseille, France; and AP-HM, Marseille, France
Purpose: Early developmental alterations of the human brain cortex cause severe brain malformations and are increasingly recognized as an important determinant for a wide variety of common pathologies such as autism, dyslexia, epilepsy, or speech disorders. Mutations in sushi-repeat containing protein SRPX2 cause Rolandic epileptic seizures, either with speech impairment (verbal dyspraxia) or in the context of abnormal gyration of the speech cortex (perisylvian polymicrogyria). The participation of Srpx2 in the development of the rat brain cortex and the pathophysiological mechanisms associated with the disease-causing mutations were investigated. Method: In utero silencing of rat Srpx2 in the developing cortex was obtained by electroporation of specific shRNA constructs at embryonic day 15, and was followed by the appropriate analyzes at the molecular, cellular, morphological, behavioral and electrophysiological levels. Result: In utero silencing of rat Srpx2 in the developing cortex led to impaired radial migration of projection neurons and was associated with
161 Abstracts
increased post-natal susceptibility to epileptic seizures. Wild-type rat Srpx2 or human SRPX2, but not the mutant, human pathogenic proteins, rescued the cortical phenotype. Misplaced neurons showed morphological anomalies in vivo and silenced neurons displayed altered migration ex vivo. How Srpx2 interferes with cell migration at the molecular level, and the post-natal electrophysiological consequences of the in utero Srpx2 silencing, are currently being investigated. Conclusion: Overall our study demonstrates that Srpx2 controls neuronal migration in the developing rat brain cortex, and strongly suggests that altered neuronal migration participates in epileptic disorders of the speech cortex including Rolandic epilepsy with verbal dyspraxia, and perisylvian polymicrogyria. cognitive tests assessing Full Scale Intelligence Quotient-FSIQ, attention and executive functions (Wisconsin Card Sorting Test; Visual Memory Span, subtest of Wechsler Memory Scale-Revised; Stroop Task; Category Fluency) and verbal learning and memory functions (California Verbal Learning Test) were done in all patients within 2 weeks of EEG recordings. Result: The initial EEG demonstrated epileptiform abnormalities in 26, focal slowing in 1 and both in 3 patients. The localization of abnormality was frontal in 10, centro-temporal in 9, occipital in 4, central in 2, temporal in 1, parietal in 1, and generalized in 3 patients. Epileptiform potentials were activated by sleep in 12 patients. Epileptiform activity was frequent in 13, moderate in 2 and rare in 14 patients. The characteristics of EEG abnormality persisted in consecutive recordings of 15 patients after 9 to 24 (mean: 15.44.7) months. Initial EEG abnormality (focal in 13 patients and generalized in 1 patient) normalized after 3 to 42 (mean 14.19.9) months. Comparison of consecutive intellectual functioning parameters in patients with persisting epileptiform potentials and patients with normalized EEG did not demonstrate a significant change. Conclusion: The intellectual functions in patients with ADHD and/or LD seems not to be affected by the presence of EEG abnormalities.
p552 IGE OF LATE ONSET VERSUS IGE OF CLASSICAL ONSET A. Valavanis, M. Spilioti, G. Zafeiridou, A. Safouris, T. Gatsios, A. Chatziapostolou, and A. Karlovasitou Medical School, Aristotle University, Thessaloniki, Greece
Purpose: Idiopathic generalized epilepsies (IGEs) are age-related epileptic syndromes mainly starting in childhood or adolescence and are considered to be rare after the second decade of life. The aim of this study is to compare two groups of patients with IGEs, those with the classical onset and those with the late one. Method: Patients with IGE, treated at the outpatient epilepsy clinic (Medical School, Aristotle University, Greece) were retrospectively screened. Population was stratified into two groups: 118 patients with seizure onset at <20 years (classical IGE) and 28 patients with onset at 20 year (late onset IGE). The inclusion criteria were: unequivocal diagnosis of IGE and normal brain imaging. Demographic data, seizure types, epileptic syndromes, neuroimaging and EEG findings were also analyzed. Result: A total of 146 Patients (mean age at seizure onset 17.8 years, range 856, SD 7.24) with IGE were identified: juvenile absence epilepsy (n:4, range 1016, SD 2.8), juvenile myoclonic epilepsy (n:89, range 8 56, SD6.5) and epilepsy with generalised tonic-clonic seizures only (n:53, range 1055, SD 8.39). The distribution of epilepsy syndrome with generalized tonic-clonic seizures (GTCSs) only, differ significantly in a group comparison (p< 0.05). The other clinical and EEG parameters did not differ throughout the groups. Conclusion: The generalized epileptic syndrome with GTCSs only, was significantly higher in the group of late onset patients, but no other differences of electroclinical features were found between the two age related groups. Our study cannot confirm that IGE of late onset might be a separate nosological entity.
p554 THE CLINICAL VALUE OF THE INCOMPLETE HIPPOCAMPAL INVERSION IN EPILEPTIC AND NONEPILEPTIC PATIENTS E. Sasso*, E. Bortone*, I. Florindo*, D. Cerasti, and G. Crisi *Neurology Unit, Parma, Italy; Neuro-Radiology Unit, Parma, Italy
Purpose: Isolated incomplete inversion of the hippocampus (IIHH), as defected fetal development, has been described in epileptic and more rarely in non epileptic subjects. We investigated the clinical features of a patient cohort presenting this morphologic variation and no other developmental abnormalities at MRI. Method: 34 consecutive patients with evidence of IIHH at 3T-MRI performed with epilepsy protocol have been included in the study. Type and course of epilepsy, standard EEG, responsiveness to AEDs, neuropsychological assessment, IIHI side have been collected for each subject. Result: Median age of patients (M= 14; F= 20) was 41 yrs and median epilepsy onset was 12 yrs. Only 6 out of 34 had no diagnosis of epilepsy. In the epileptic cohort partial seizures were more commonly reported (82%) with or without secondary generalization. Febrile convulsions earlier in life have been described in 4/28 cases. 8/28 had refractory epilepsy whereas the remaining 20 were at time satisfactorily controlled. 33 out of 34 patients presented a left-sided IIHH. Side correlation between EEG and IIHH was impressively higher (85%) than in previous studies with regard to epilepsy cohort. Minor to mild cognitive impairment has been observed in only 3 subjects. Hippocampal morphometric investigations leading to estimate the different involvement of hippocampal regions (head, body, cauda) are still in progress. Conclusion: IIHH is a discrete hippocampal malformation often leading to epilepsy. Present study confirms that non epileptic subjects are rare and that left-sided IIHH and EEG adherence can help to calibrate the epileptogenicity risk and maybe refractory sources.

p553 NATURAL PROGNOSIS OF EEG ABNORMALITIES AND INTELLECTUAL FUNCTIONS IN CHILDREN WITH ADHD AND/OR LD D. Turkdogan, and S. Zaimoglu Marmara University, Istanbul, Turkey
Purpose: We aimed to study evolution of EEG abnormalities in children with ADHD and/or LD. Method: In 30 (aged 714, mean: 8.21.9 years, 7% female) patients with ADHD and/or LD and an abnormal EEG, serial EEG examinations were done in an interval of 3 to 42 months. Comprehensive battery of
p555 PREDICTORS OF NEURODEVELOPMENTAL OUTCOME FOLLOWING EPILEPSY ONSET IN INFANCY H. OReilly*, K. Verhaert, C. M. Eltze, H. Cross, R. Scott*, and M. De Haan* *University College London, London, UK; and Great Ormond Street Hospital for Children NHS Trust, London, UK
Purpose: Infant onset epilepsy is associated with poor neurodevelopmental outcome. Determining predictors of outcome is important in idenEpilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x
162 Abstracts
tifying those children most at risk for developmental compromise. The aim of this prospective population-based study was to identify neurological predictors of cognitive outcome in children at 35 years of age with epilepsy onset < 2 years. Method: Children < 2 years of age presenting with recurrent unprovoked seizures from a defined area of North London were enrolled over two years. Clinical assessments and neurodevelopmental evaluation were performed at enrolment using Bayley Scales of Infant and Toddler Development-III and at follow-up using the Leiter-R. Multiple regression analysis was used to establish the relationship between individual clinical and investigative results and later cognitive outcome. Result: Data from baseline and 3 year follow-up were available for 40 children (25 male, age onset M=6.7months, age follow-up M= 48.8months). At follow-up 55% had an IQ > 2SD below the mean. Lack of seizure control, abnormal EEG and cognitive score at baseline accounted for 78.8% of variation in IQ/cognitive scores (R =0.888, R2 =0.788). Conclusion: 55% of the children with infant onset epilepsy were developmentally delayed at 3-year follow-up. Abnormal EEG, cognitive score at presentation and lack of seizure control predicted function at follow up. These findings suggest that children who are performing poorly at baseline continue to display delayed development at follow-up and this delay is related to continuing seizure activity. Purpose: Studying of BEDC (benign epileptiform discharges of childhood) in EEG of children with infantile cerebral paralysis (ICP). Method: The study had 29 subjects aged between 3 months and 13 y.o. with brain organic lesions with and without motor impairment. Focal epilepsy was diagnosed in 9 on 15 of the I group subjects. ICP variations (Cerebral Palsy) distribution was as follows: tetraparesis in 10 children, hemiparesis in 2 children, and spastic diplegia in 2 children. During the study BEDC were diagnosed for the first time in subjects of both groups. A number of EEG assessments were carried out with once-a-month frequency. The exclusion criterion was diagnosed benign childhood epilepsy with central-temporal spikes. Result: At the moment of the study launch EEG of all children showed different alterations: delay in principal EEG rhythm generation; slowwave focal activity; epileptiform complexes; sharp-slow wave; spikeslow wave. Dynamic EEG showed in all children participating in the study complexes of benign epileptiform discharges of childhood. We noticed that appearance of these patterns in EEG coincided with clinical improvement of motor abilities in the I group subjects irrespective of brain lesions volume. In the I group subjects BEDC persisted throughout the entire study but showed certain mobility within brain cortex. Conclusion: 1. BEDC in our study were transitory in children without motor impairment. 2. Possibly BEDC might not impair motor abilities, but predict recovery from hereditary impairment of brain maturation
p556 DEVELOPMENT AND BEHAVIOR OF CHILDREN AGED 2 TO 5 YEARS AFTER EXPOSURE TO ANTIEPILEPTIC MONOTHERAPY IN UTERO N. Cossa, H. Garlipp, R. Kretz, A. Lscher, P. Senf, B. Wandschneider, and B. Schmitz Vivantes Humboldt Klinikum, Berlin, Germany
Purpose: Within GRAP (German Registry of Antiepileptic Drugs in Pregnancy, which is associated with the EURAP-Project) we have conducted a questionnaire study focusing on the development between the 2nd and 5th year of life. Method: Participants were 346 mothers whose children were between 2 and 5 years. Inclusion period was 20072010. For this analysis we selected 248 children exposed to one of the three most common monotherapies: valproate (VPA, N = 51), lamotrigine (LTG, N= 140) or cabamazepine (CBZ, N = 57). Mothers completed standardized questionnaires of child development (MCDI = Minnesota Child Development Inventory) and mental disorders in childhood (CBCL = Child Behavior Checklist) annually. Result: Significant differences were found for two subscales of the CBCL at age 2. VPA exposed children had higher scores in the emotional reactive category compared to LTG exposed children (U = 46, r =-0.38, p < 0.017) as well as higher scores for the variable attention problems compared to the CBZ group (U = 7, r =-0.40, p < 0.017). There were no differences at age 3, 4 and 5. Conclusion: The results confirm VPA associated developmental problems in children exposed to VPA in utero. These differences were only found at the young age of two years. The investigation group was small and selection bias cannot be ruled out. However, our results suggest that developmental problems may disappear with age.
p558 SEIZURE OCCURRENCE DURING PEDIATRIC EEG R. Gandelman-Marton, E. Heyman, and E. Lahat Assaf Harofeh Medical Centre, Zerifin, Israel
Purpose: The ictal EEG can reveal previously unreported seizures and correct seizure classification and misdiagnosis of epileptic and nonepileptic seizures. Prolonged video- EEG recording can substantially increase the diagnostic yield of seizures, but this test is less accessible than routine EEG. The aim of our study was to identify the patients who are more likely to experience a seizure during short-term EEG recording. Method: We retrospectively reviewed the EEG recordings and medical records of 294 patients, who were admitted to the Pediatric Departments in Assaf Harofeh Medical Center, and referred for a short-term EEG during a 5-year period following a seizure. Result: Fifteen (5.1%) patients had seizures. The likelihood of seizure occurrence was increased by history of seizures (OR 11.86, 95% CI 2.54 to 55.37), abnormal neurological examination (OR 3.33, 95% CI 1.05 to 10.55), and the presence of interictal epileptiform discharges (OR 10.07, 95% CI 1.26 to 80.42). Treatment with antiepileptic drugs and mental retardation were significantly more common among patients with seizures. Conclusion: Children with a higher likelihood of a seizure during shortterm EEG can be identified using data mainly obtained by history and neurological examination.
p557 MOTOR IMPAIRMENT DURING THE FORMATION OF BENIGN EPILEPTIFORM DISCHARGES OF CHILDHOOD. TRUE OR FALSE? D. Zaytsev, L. Eletskova, D. Lutin, and N. Titov Zaytsev's Neuropsychiatric Center, St. Petersburg, Russian Federation
p559 MISLEADING GENERALIZED REFRACTORY EPILEPSY IN YOUNG CHILDREN EVOLVING TO SYMPTOMATIC OR PROBABLY-SYMPTOMATIC FOCAL EPILEPSY; EPILEPSY SURGERY CANDIDATES LATE DETECTION POSSIBLE REASON TO BE CONSIDERED A. Dalla-Porta, I. Maestro Saiz, J. M. Prats Vias, A. I. Fernndez-Bedoya, B. Mateos, L. Perez, and I. Yurrebaso Cruces University Hospital, Barakaldo, Spain
163 Abstracts
Purpose: Refractory epilepsy in children should be treated precociously in order to avoid cognitive impairment among others. We present four children with heterogeneous epileptic syndromes initially diagnosed of misleading generalized epilepsy. Method: The four children aged from 18-months to 11 years, were studied in our institution since neonatal age because of neonatal refractory epilepsy. All of them underwent prolonged video-EEG recording and structural neuroimaging and metabolic and genetic studies. Ictal semiologic and electrographic changing patterns of recorded seizures were analyzed along epilepsy evolution. Result: Metabolic and genetic studies were normal and structural neurimaging revealed focal structural abnormalities in all cases, mostly not identified until later stages. In early video-EEG recordings, symmetric or asymmetric epileptic spasms, generalized tonic or tonic-clonic seizures or generalized myoclonic seizures with also generalized epileptiform ictal activity were recorded. In later stages, partial seizures such as, versive, dialeptic or automotor seizures with ictal focal epileptiforms patterns with or without secondary generalization were identified. At present, two of the four patients are considered for epilepsy surgery and the other two will undergo further functional and structural imaging studies just to be considered for surgery. Conclusion: These epileptic children were initially diagnosed of generalized epilepsy as a result of initial clinical, video-EEG and structural neuroimaging data. The epilepsy diagnostic in these patients, evolved to symptomatic or probably-symptomatic focal epilepsy being then, considered for epilepsy surgery. Children presenting signs suggesting generalized epilepsy in early stages should not be excluded for further studies in order to determine if they are not real epilepsy surgery candidates. Purpose: Dravet syndrome is characterized by recurrent prolonged convulsions usually associated with febrile illness. Many gene mutations have been described behind the syndrome; however the mechanism of why do seizures occur is not yet very clear. In addition, patients with Dravet seem to be predisposed to recurrent infections. Method: In this article a girl who presented with prolonged convulsions associated with recurrent infections was diagnosed to have Dravet syndrome in relation with a new mutation. In addition, she was found to have immunoglobulin g subclasses deficiency. Result: The case illustrates that immunodeficiency may be behind the frequent infections triggering the seizures in Dravet syndrome. Conclusion: Treating the immunodeficiency might help patients with Dravet syndrome in reducing the frequency of their illness and subsequently their convulsions.
p562 ATYPICAL FOR ROLANDIC EPILEPSY D. Musralina Almaty State Institute of Advanced Medical Education, Almaty, Kazakhstan
Purpose: To research the atypical for child benign partial epilepsy with centro-temporal spikes (Rolandic epilepsy) and to define the treating tactics. Method: A clinical case of child benign partial epilepsy with centrotemporal spikes at the girl. Result: The child is from second pregnancy, which occurred with CMV, HSV in early period. The neonatal period - restless sleep and regurgitation. The first seizures occurred at 1 year and 10 months, the second episode - was after the affective-respiratory paroxysm; the third - was triggered by negative emotions. Seizures proceeded by an aura - an abdominal pain and depressed mood. Later they were joined by the partial attacks - the numb or the weakness in the left half of the face, left hand, also the speech disorder during the attack, finished with the subsequent generalization. Neuropsychological development was not affected. EEG (at the 2 years old) - benign epileptiform patterns of childhood in the right temporal region. MRI of the brain - no significant changes. She was appointed to the drug valproic acid, which is replaced by topiromat, because of the lack of effect. In the dynamics the attacks were held, became more frequent. The EEG pattern was persisted, which was corresponded to rolandic epilepsy. After correction therapy (sul'tiam 5mg/kg) convulsions were managed. Catamnesis has demonstrated control of seizures and improvement of health during 4 years. Conclusion: The presented clinical case shows an atypical variant of Rolandic epilepsy: early age of onset, debut with affective seizures, generalized seizures, abdominal sensory aura, necessity to use the classic antiepileptic drugs.
p560 THE RISK FACTORS OF RECURRENT FEBRILE CONVULSION B. H. Cha Yonsei Unversity Wonju College of Medicine, Wonju, Korea
Purpose: Febrile convulsion is the most common type of seizure disorder during childhood. We would like to evaluate the risk factors associated with the recurrence of febrile convulsion. Method: We retrospectively reviewed the medical records of 470 pediatric patients aged from 6 months to 5 years old, who admitted to the Wonju Christian Hospital from January, 2008 to December, 2009 for febrile convulsion. We evaluated the recurrence rate of febrile convulsion by age of onset, duration of convulsion, seizure types, numbers of the recurred seizures during the initial 24 hours after the first convulsion, and family history of febrile convulsion or epilepsy. Result: The ratio of male and female is 1.33: 1. The 69.8% of patients experience the first febrile convulsion between 12 and 23 months old. The cumulative rates of the recurred cases by the intervals between the initial and recurred febrile convulsion are 51.9% at 6 month, 82.6% at 12 month, and 89.8% at 24 month. The recurrence rate of febrile convulsion is 56.2% and when the first febrile convulsion occurs at the age less than 12 months old, the recurrence rate (67.6%) is higher than the other age of onset. There are no differences of recurrence rates by the duration of convulsion, seizure types, the numbers of recurred seizures during the initial 24 hours, and the family history of febrile convulsion or epilepsy. Conclusion: We should closely observe the patients the first febrile convulsion occurs at the age less than 12 months old and need to educate the parents.

p563 RECOVERY IN CHILD WITH ACQUIRED APHASIA AND EPILEPSY S. M. Golubovic, and M. Risovic Faculty of Special Education and Rehabilitation, University of Belgrade, Belgrade, Serbia
p561 A GIRL WITH DRAVET SYNDROME AND IMMUNOGLOBULIN G SUBCLASSES DEFICIENCY D. A. Hasbini Rafic Hariri University Hospital, Beirut, Lebanon
164 Abstracts
Purpose: Boy was born such as first child from first pregnancy which is ordinarily contorlled, maintained till 8. month with gynipral. Birth was spontanious on the beggining of 9. month. WB (weight on birth) was 2150 gr. PD 45 cm, AS 8. Child is born with hearth defect (VSD). Method: Psyhomotoric development was regular, begun to walk in 13. month, begun to speak in 11 month. He was operated and postoperatively, after waking up from anasthesia child had convulsional crisis (510 during day, lasting 10 days), hemyparesis lat. sin., lost of alredy developed abilities, divergent strabysmus, not controlled watering/miction and defecation. Since than, he gets antiepyleptics (targetol) because of EPY attacs in short sequences pariet-occipital right, and independent epyleptogene focusis frontal-central-temporal Result: Hemiparesis appeared as consequence of operation of hearth. Child was in coma for 7 days, lost eyesight, hearing and motorics. He had EPY attacs. Conclusion: Child had physical and logopedic tretament and he begun to contole defecation and miction. He wears plasters, alternatively on left and right eye, because of strabismus. In neurological status is dominating damage of fine motorics. He is comunicative, cooperates, imitates acting of other people. Purpose: Study of the effectiveness of polytherapy in children with pharmacoresistant epilepsy. Method: We observed 25 children (11 girls, 14 boys) with pharmacoresistant epilepsy, aged from 6 months to 14 years. Result: The cases were symptomatic (16), idiopathic (6) forms of epilepsy and epileptic encephalopathies (3). Epilepsy in the background of the congenital malformation of the brain - 6, CP - 4, atrophic process - 3, after suffering a stroke - 2, after removal of the arachnoid cyst - 2, microcephaly - 1, CMV infection 1, cause is not known - 6. Routine EEG: recorded epileptiform activity in 19 children, 6 children are not registered. MRI: organic brain changes (16), with no apparent pathology (9). Combinations of drugs: VPA + TPM (6); LEV + VPA (5); VPA + CBZ (3); VPA + LTG (2); VPA + LEV + TPM (2); VPA + OXC (1); VPA + TPM + CBZ (1); VPA + TETRACOSACTIDE (1); LTG + CBZ (1); LTG + LEV (1); LEV + TPM (1); TPM + CBZ (1). The effectiveness of therapy was observed in the form of complete control of seizures - 10, of 50% and above - 5, of 3050% - 8, no effect - 2. Conclusion: Pharmacoresistant Epilepsy occurs predominantly in symptomatic forms (64%). In 16 (64%) had organic brain changes. In 40% (25 children) experienced complete control of seizures, improvement in 52% of children with no effect in 8% of children. It should be noted with sufficient effectiveness of polytherapy of pharmacoresistant epilepsy.
p564 CORRELATIONS OF CLINICAL AND RADIOLOGIC FEATURES IN PEDIATRIC PATIENTS WITH SCHIZENCEPHALY I. Kopyta, E. Jamroz, E. Kluczewska, and B. Sarecka-Hujar Medical University Of Silesia, Sosnowiec, Poland
Purpose: Schizencephaly is a rare and severe congenital brain defect. Its etiology is not unequivocal. Aim of the study was to analyze correlations between clinical and radiologic features of schizencephaly in Polish pediatric patients. Method: Study group consisted of 22 children (7 girls; 15 boys, aged: 3 months-17 years). Patients were diagnosed at the Department of Neuropediatrics in Katowice. Result: Epileptic seizures were observed in 64% of cases. In the follow-up the evolution of the seizures features was observed to the focal motor seizures, primarily or secondarily generalized tonic-clonic seizures, tonic seizures, atypical absence. Eight of the patients were seizure-free. In 32% of patients the epilepsy was drug-resistant. The generalized hypotonia was found in 14%, the spastic quadriparesis in 55% and spastic hemiparesis in 32% of cases. We observed that seizures were more frequent in the subgroup of children with bilateral schizencephaly than in unilateral schizencephaly (80% vs 29%, p=0.019). The correlations between presence of the bilateral type II schizencephaly and occurrence of the seizures and atypical absence were found (p=0.004 and p=0.011, respectively). Conclusion: There is a correlation between the type of schizencephaly and presence of the seizures in Polish pediatric patients. In most of the patients schizencephaly leads to developmental retardation and epileptic seizures.
p566 DOUBLE CORTEX SYNDROME AND EPILEPSY R. I. Teleanu*, M. Sandu, D. Vasile, D. Teleanu, and D. Plesca *Carol Davila University of Medicine, Bucharest, Romania; Dr V Gomoiu Children's Hospital, Bucharest, Romania; and Emergency University Hospital, Bucharest, Romania
Purpose: Subcortical laminar heterotopia or double cortex is a cerebral malformation with a defect in neuronal migration. Clinical manifestations are epilepsy and mental retardation. This disorder mainly affects females. The XLIS gene is implicated and it is localized on the Xq22.323 chromosome. Method: We present 3 rare cases diagnosed with subcortical laminar heterotopia. Result: All patients had epileptic seizures, all patients had dysarthria and one patient had mental retadation. MRI revealed in all patients a double cortex aspect. Single Photon Emission Computed Tomography (SPECT) was performed in one patient. Conclusion: In the past, such cases were categorized as cryptogenic epilepsy. Neuronal migration disorders associated with epilepsy can be recognized by modern techniques, particularly MRI.
p565 ANALYSIS OF THE EFFECTIVENESS POLYTHERAPY IN CHILDREN WITH PHARMACORESISTANT EPILEPSY N. Mendigaliyeva*, and D. Ayaganov *Almaty State Institute Of Advansed Medical Education, Almaty, Kazakhstan; and Almaty, Kazakhstan
p567 THE RESULTS OF NIGHT SLEEP ELECTROENCEPHALOGRAPHY AND MRI IN CHILDREN WITH EPILEPSY O. Klochkova, O. Kozhevnikova, L. Namazova-Baranova, A. Anikin, O. Logacheva, and V. Altunin Scientific Centre of Children Health, Moscow, Russian Federation
Purpose: Assess the possibilities of long time electroencephalography (EEG) during the night sleep in diagnostics of epilepsy; to compare night EEG results with magnetic-resonance imaging (MRI) findings in children with epilepsy.
165 Abstracts
Method: 83 children (3 months12 years old) with epilepsy underwent routine EEG (REEG) on digital electroencephalography machines NicOne (Nicolet, USA) during 20 minutes and then EEG during all night. Children under 3 years, some after 3 years underwent REEG during the day sleep. All patients had epilepsy, treated in out-patient department. All children had pathology according to perinatal anamnesis. Brain MRI was done on Signa Twin speed Excite 1.5 T1 (GE, USA) in 54 patens. Result: 37% of children had generalized or local epileptiform activity on REEG, and 69% - on night EEG. Only 23% patients had the generalized epileptiform activity on routine EEG in comparison with 75% on the night EEG, 11% patients had the focal epileptiform activity (REEG) in comparison with 22% during night EEG, and 9% had combined activity on REEG, and 43% - on night EEG. Only during night EEG we detected 3 cases of seizures during investigations. 69% patients had alterations of structure of brain on MRI. Among structural disorders dominated local subatrophy, arachnoid cysts and ventriculomegalia. We didn't see correlation between structural deviations on MRI and degree of night EEG changes. Conclusion: We recommend to carry out night EEG in children with seizures and pathological changes on REEG as more informative and useful method, after first seizures or during epilepsy and without changes on REEG. tumor histology, location, changes in the peritumoral brain parenchyma and genetic predisposition. The aim of presented research was studying epileptogenic potential of brain tumors of different histologic types in children. Method: Among the pediatric patients investigated and treated in the Neurosurgical Department and Psycho-Neurological Department No2 of Russian Children Clinical Hospital at the period 20062011 were revealed 60 children with supratentorial brain tumors. Result: The group of patient (n=60) consists of 28 girls and 23 boys (age range from 17 month till 17 years). 41 patients (68.3%) had symptomatic epilepsy. Among the patients were revealed: fibrillary astrocytoma 8 cases (all 8 patients had epilepsy), pilocystic astrocytoma 6 (3), pleomorphic xanthoastrocytoma 5 (4), desmoplastic infantile astrocytoma (DIA) 1 (0), protoplasmic astrocytoma 2 (1), ganglioastrocytoma 5 (5), mixed glioma 3 (1), mixed ganglioglioma 2 (1), anaplastic ganglioglioma 1 (0), desmoplastic ganglioglioma 1 (1), glioblastoma multiforme 2 (2), olygodendroglioma 1 (0), anaplastic ependymoma 6 (3), choroid plexus papilloma 3 (0), atypical choroid plexus papilloma 1 (1), choroid plexus carcinoma 1 (0), dysembryoplastic neuroepithelial tumor (DNET) 5 (5), primitive neuroepithelial tumor (PNET) 1 (1), atypical meningioma 1 (1), thalamic hamartoma 3 (3), meningioangiomatosis 2 (2). Conclusion: Tumor types demonstrated obligate epileptogenesis were: fibrillary astrocytoma, ganglioastrocytoma, DNET, PNET, hamartoma, meningioangiomatosis, desmoplastic ganglioglioma, glioblastoma multiforme and atypical meningioma. Pleomorphic xanthoastrocytoma was epileptogenic in 80% of cases. Pilocystic and protoplasmic astrocytoma, mixed ganglioglioma, anaplastic ependymoma had 50% risk of epilepsy.
p568 FEATURES OF THE PITUITARY HORMONAL REGULATION IN CHILDREN AND ADOLESCENTS WITH EPILEPSY Z. Viksna*, Z. Viksna, J. Strautmanis, A. Kovaldins, and R. Ligere *Private, Jelgava, Latvia; Children's University Hospital, Riga, Latvia; and Paul Stradin's University Hospital, Riga, Latvia
Purpose: To evaluate changes in mean level of pituitary hormones- luteinising hormone (LH), follicle-stimulating hormone (FSH), and sex steroids- testosterone, oestradiole in blood serum in children and adolescents with epilepsy. Method: The retrospective, case-control research envolved 53 patients (27 girls 50.9% and 26 boys - 49.1%) aged 6 months until 18 years with "Idiopathic epilepsy or "Symptomatic epilepsy. Age groups: 011 years (17 girls and 20 boys), 1218 years (10 girls and 6 boys). We determined mean levels of LH, FSH, testosterone and oestradiole in blood serum 30 minutes till 24 hours after the epileptic attack using the enzyme linked immunosorbent assay. Result: In 43 of the 53 observed patients (81.1%) we stated hormonal changes. LH was reduced in 17 girls (62.9%) and 19 boys (73.1%) in the age group 011 years, increased in 2 boys (7.7%) in the age group but 1218 years. FSH was reduced in 6 boys (23.1%), but elevated in 2 girls (7.4%). Oestradiole was lower in 9 girls (33.3%) in the age group 011 years. Testosterone was lower in 17 boys (65.4%) and 2 girls (7.4%). Conclusion: Clinical observations reveal that children with epilepsy aged 011 years demonstrate pituitary and sex steroid hormonal alterations claiming for accurate, both clinical data, analysis.
p570 SEIZURE OUTCOME AFTER SERIAL AEDS HAVE FAILED FOR LACK OF EFFICACY IN FOCAL EPILEPSY IN CHILDREN WITHOUT AN ELECTROCLINICAL SYNDROME E. Wirrell, K. Nickels, and L. Wong-Kisiel Mayo Clinic, Rochester, MN, USA
Purpose: To determine outcome after serial AEDs fail for lack of efficacy in a population-based cohort of children with new-onset focal epilepsy without defined electroclinical syndrome (FE-ES). Method: Children with new-onset FE-ES diagnosed from 19802009 in Olmsted County, MN were identified. Those followed >2 years following initial diagnosis were studied. We evaluated long-term outcome [stratified into favorable (seizure free >1 year at final follow-up and no prior resective epilepsy surgery), or poor (seizures in the final year of follow-up or prior epilepsy surgery)] in children where zero, one, two, or three or more AEDs had been ineffective. Result: 276/468 (59%) cases of newly-diagnosed pediatric epilepsy had FE-ES, and 246 (89%) were followed for >2 years (median follow-up 10 yrs). Of these, 160 (65%) achieved a favorable outcome. Favorable outcome was significantly less likely with increasing numbers of failed AEDs (p<0.001), being seen in 140/171 (82%) in whom none failed, 14/ 37 (38%) in whom 1 failed, 6/14 (42%) in whom 2 failed, and 0/24 (0%) in whom >3 AEDs failed. Although our numbers were small, children with structural etiologies tended to have lower favorable outcome rates than those of unknown cause after one (25% vs 56%) or two AEDs (22% vs 80%) had failed (p=0.06). Conclusion: FE-ES accounts for over half of pediatric epilepsy. While two-thirds have a favorable outcome after long-term follow-up, the chance of this outcome drops sharply after the first AED fails. Favorable outcome was not seen in any child for whom >3 AEDs had failed for lack of efficacy.
p569 EPILEPTOGENIC POTENTIAL OF SUPRATENTORIAL BRAIN TUMORS IN CHILDREN A. A. Kholin, and V. S. Khalilov Russian State Medical University, Moscow, Russian Federation
Purpose: Symptomatic epilepsy is common in patients with supratentorial brain tumors. Epileptogenesis depends on several factors including
166 Abstracts
p571 CYTOKINE LEVELS IN CHILDREN WITH IDIOPATHIC PARTIAL AND GENERALIZED EPILEPSY TREATED WITH TOPIRAMATE AND VALPROIC ACID F. M. Sonmez*, M. Serin, A. Alver, D. Zaman, R. Aliyazicioglu, A. Cansu, and B. Anlar *Faculty of Medicine, Fatih University, ANKARA, Turkey; Karadeniz Technical University, Trabzon, Turkey; and Faculty of Medicine, Hacettepe University, Ankara, Turkey
Purpose: Antiepileptic drug (AED)s have been reported to affect the production and levels of certain cytokines. We investigated the effects of valproic acid (VPA) and topiramate (TPM) on the levels of interleukin IL1a, IL-1b, IL-1 receptor antagonist (IL-1RA), IL-2, 6 and 10, and Tumor necrosis factor -a (TNF-a) in children with idiopathic epilepsy. Method: Forty prepubertal children aged 612 (mean 8.3 1.7) years with idiopathic epilepsy were included. The patients were divided into two groups: 20 were treated with valproic acid (VPA) and 20 with topiramate (TPA). The plasma levels of IL-1a, IL-1b, IL-1RA, IL-2, 6 and 10, TNF-a were measured before the initiation and at the 6th and 12th months of the treatment. Result: In the VPA group, the levels of IL-1 significantly increased at 12 months while the levels of IL-10 decreased at 6 months of treatment compared to values before treatment (p<0.05). There was no significant difference in levels of IL-1, IL-6, TNF-a (p>0.05). In the TPM group, lower levels of IL-10 were observed at 6th and 12th months compared to the onset of treatment (p<0.05). Conclusion: VPA and TPM may affect cytokine levels. The next step would be to investigate the relation of these findings to the outcome of epilepsy and response to treatment. In addition the clinical significance of these effects on the immune system, autoimmunity, or inflammation needs to be examined in a long-term, prospective manner. Conclusion: Language reorganization in BECTS patients obviously focuses on the anterior language areas. These functional changes can be interpreted as important compensatory strategies of the CNS to stabilize cognitive, especially language performances.

p573 THE EFFECTIVNESS OF THE CARBAMAZEPINE TREATMENT IN THE JUVENILE MYOCLONIC EPILEPSY B. Lorber, M. Vivoda, and D. B. Voduek University Hospital Centre, Ljubljana, Slovenia
Purpose: To determine how often CBZ is used in the treatment of JME, despite it is considered inappropriate AED to use in this syndrome as it may aggravate absence and myoclonic seizures characteristic of JME. Do patients that react favourably to CBS represent clinically different subtype of JME Method: A retrospective study, using patient records from the specialised epilepsy clinic. Result: From 96 patients with JME, 30 patients were treated with CBZ at some stage in the course of therapy. Treatment was considered effective and tolerable for 68% of the patients treated with CBZ and in 96% of the patients treated with other anti epileptic drugs (mostly VPA and LTG). Replacing CB with theoreticaly more appropriate therapy was advised for all the patients treated with CBZ. In 72% of these patients the new treatment was considered effective and tolerable. Initial CBZ treatment of JME resulted in much less favourable prognosis than initial treatment with other AED. Conclusion: Treatment of JME with CBZ is not uncommon and was found surprisingly effective in our group of patients. A part of it may be attributed to sub-optimal history taking regarding myoclonic seizures when JME was not properly diagnosed. But some of those patients may also represent a subgroup in the JME syndrome with major clinical feature of JME but different response to AED and possibly different etiopathological mechanisms.
p572 COGNITIVE IMPAIRMENT AND CORTICAL REORGANISATION IN CHILDREN WITH BENIGN EPILEPSY WITH CENTRO-TEMPORAL SPIKES (BECTS) A. N. Datta*, N. Oser, F. Bauder, O. Maier, F. Martin, G. P. Ramelli**, M. Steinlin, P. Weber*, and I. K. Penner *University Children's Hospital, Basel, Switzerland; University of Basel, Basel, Switzerland; Children's Hospital, Lucerne, Switzerland; Children's Hospital, St. Gallen, Switzerland; Children's Hospital, Aarau, Switzerland; **St. Giovanni Hospital, Bellinzona, Switzerland; and University Children's Hospital, Berne, Switzerland
Purpose: Benign epilepsy with centro-temporal spikes (BECTS) is associated with mild cognitive deficits, especially language impairment. Functional correlates of neuropsychological language deficits and the impact of duration and antiepileptic treatment on language reorganisation were investigated. Method: 28 patients with BECTS and 19 healthy controls underwent neuropsychological testing and functional magnetic resonance imaging (fMRI). Result: Although neuropsychological test results did only differ by trend between BECTS patients and controls, language laterality indices (LIs) in fMRI were significantly lower in patients than in controls. Particularly the anterior language network with Broca's area and the supplementary motor area (SMA) revealed the lowest LIs. Medication and duration of epilepsy did not have any significant impact on language reorganisation and patients performances.
p574 AN EXPLORATION OF PRESCRIBING PRACTICE AND PARENTAL USE OF EMERGENCY RESCUE MEDICATION TO PREVENT STATUS EPILEPTICUS IN CHILDREN C. M. Brand, and A. Mclellan Royal Hospital for Sick Children NHS Lothian, Edinburgh, UK
Purpose: To review current clinical practice around the prescribing of emergency medications for prolonged seizures and whether parents who have been trained can give and use it correctly. Method: Data was collected prospectively for 6 months from a nurse led clinic in a paediatric tertiary care centre in south east Scotland. Using an audit questionnaire each patient attending the clinic had their emergency medication prescription reviewed and assessed against the in-house emergency medication prescribing pathway. Families were asked if they had used emergency medication and were assessed on whether they could demonstrate administration technique correctly. Result: 49 patients were prescribed emergency medication for prolonged seizures. 47 (96%) patients had been admitted to hospital for
167 Abstracts
prolonged seizures prior to prescription of emergency medication and only 23 (47%) patients were admitted following prescription of emergency medication. 48 (98%) patients had been prescribed emergency medication appropriately for prolonged seizures with 1 inappropriately prescribed for dose and only 34 (71%) had careplans completed. All parents had been taught administration technique, only 39 (79%) were able to demonstrate the correct technique to deliver their child's prescribed emergency medication. 29 (59%) parents reported using it when required, where they would have otherwise have called an ambulance with 4 choosing not to use it and 16 unknown as it had not yet been required. Conclusion: Emergency medication for prolonged seizures is generally prescribed appropriately, reduces the numbers of calls for an ambulance but not all parents can correctly demonstrate the technique of administrating emergency medication. Further work is required to ensure that careplans are always completed. stimuli and may affect function, behavior and quality of life in a negative manner. The sensory profile of children with generalized epilepsy has not been fully clarified. Purpose: Assess possible sensory processing disabilities within all sensory modalities in children with generalized epilepsy. Method: Patients: 52 children at the age of 610.9 years participated including 22 patients with generalized epilepsy compared with 26 age and gender matched controls. Methods: A standardized Short Sensory Profile (SSP) questionnaire including 38 items was given to caregivers to report, measured tactile and taste/ smell sensitivities, movement sensitivity; underresponsive/seeks sensation, auditory filtering, low energy/weak sensation and visual/auditory sensitivity. Result: Children with generalized epilepsy had significantly higher sensory processing disabilities in all sensory modalities compared with controls and even showed extreme patters of underresponsive/sensation seeking. Conclusion: The present study further delineates the growing bulk of data recognizing generalized epilepsy among children as a multi-faceted neurological disorder with diverse functional disabilities including sensory processing dysfunction, even showed extreme patters of underresponsive/sensation seeking.
p575 BLINK RELATED TEMPORAL SPIKES IN BENIGN ROLANDIC EPILEPSY D. Allen, F. Cave, and F. Kirkham Wessex Neurological Centre, Southampton General Hospital, Southampton, UK
Purpose: Age-related cortical hyper-excitability is considered to be an underlying abnormality in the benign childhood focal epilepsy syndromes, resulting in functional spikes, benign seizure syndromes and in some cases extreme SEPs induced by finger tapping in some cases of BRE. Only one previous case of blink related spikes in BRE has been reported. Method: We report the case of a girl who presented in status epilepticus aged seven. MR Imaging was normal. Subsequent infrequent seizures were typical of BRE. EEG recordings revealed right mid-temporal spikes evoked only by spontaneous blinks. Left centro-temporal spikes occurred unrelated to blinking. All attempts to elicit right sided spikes by other means failed. Result: A one hour video-EEG was recorded to characterise the spikes. 998 left sided spikes were seen. 74 right sided spikes occurred at a mean peak latency of 98ms (SD 9.3ms) after the onset of eye blinks, determined with EOG surface electrodes. Conclusion: The findings suggest a different mechanism to the generation of extreme SEPs. Strictly spontaneous blink related spikes were most likely due excitation of the hyper-excitable right Rolandic cortex as a consequence of an excitatory interconnection from the pre-central cortex, supporting the theory of age-related cortical hyper-excitability in BRE. Yamagata T et al JNNP 1997; 63: 528530 Nadkarni M et al Electroenc Clin Neurophysiol 1994; 90: 3639 Manganotti P et al Brain 1998; 121: 647658.
p577 SUDDEN UNEXPECTED DEATH IN CHILDREN AND TEENAGERS WITH EPILEPSY: AN EPIDEMIOLOGICAL STUDY F. M. Besag*, R. Ackers, E. Hughes, L. Nashef, W. Squier, M. Murray, and I. Wong** *SEPT: South Essex Partnership University NHS Foundation Trust, Bedford, UK; UCL, London, UK; Guys and St Thomas NHS Foundation Trust, London, UK; Kings College Hospital, London, UK; John Radcliffe Hospital, Oxford, UK; and **The University of Hong Kong, Hong Kong, Hong Kong
Purpose: To determine the rate of sudden unexpected death (SUDEP) in a population-based sample of children and teenagers aged 018 years. Method: Data were extracted over the period 1.1.93 to 31.12.05 from the General Practice Research Database (GPRD), which includes approximately 5% of the UK population and is representative of the general population. All subjects 018 years who had a diagnosis of epilepsy and were taking antiepileptic drugs were included. The cohort consisted of 6190 subjects representing 26,890 patient years. GP questionnaires, hospital letters and all other available data were examined in detail by an expert consensus panel. 151 deaths were identified. Cases were scrutinised by a second panel including an epileptologist with a special interest in SUDEP to determine cases of definite, probable and possible SUDEP. Result: Eleven subjects, 2- 17 years of age (8M, 3F) died from definite (2), probable (3) or possible (6) SUDEP. Seven had significant underlying neurological/neurodevelopmental problems: Ohtahara syndrome (1), cerebral palsy (3) and other underlying neurological abnormalities (3). However, the remaining four had no evident underlying disorder apart from the epilepsy. The SUDEP incidence rates were: definite and probable 1.9 per 10,000 person-years (95% CI 0.6, 4.3), possible 2.2 per 10,000 person-years (95% CI 0.8, 4.9), combined definite, probable and possible 4.1 per 10,000 person-years (95% CI 2.0, 7.3). Conclusion: SUDEP can occur in both children with pre-existing neurological abnormalities and those who appear to be neurologically normal apart from the epilepsy. However, the SUDEP rate was low in this population-based study.
p576 SENSORY PROCESSING DISABILITIES IN CHILDHOOD- ONSET GENERALIZED EPILEPSY E. Shahar*, S. Zlotnik2,3, S. Ravid*, and B. Engel-Yeger *Child Neurology Unit & Epilepsy Service, Meyer Children Hospital; Department of Occupational Therapy, Rambam Medical Center, Rappaport School of Medicine; and Department of Occupational Therapy, Faculty of Social Welfare and Health Studies, University of Haifa, Haifa, Israel
Background: Sensory processing disabilities (SPD's) are defined as inability to process sensory stimuli in a graded manner and to execute behaviors that are suitable to the degree, nature or intensity of the sensory
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p578 EVALUATION OF EFFICACY OF VAGUS NERVE STIMULATION IN CHILDREN. PROSPECTIVE RESULTS FROM A SINGLE CENTER IN LEBANON G. A. Hmaimess*, A. Baydoun, I. Dabaj, and H. Mansour *Saint George University Hospital Medical Center, Beirut, Lebanon; Beirut, Lebanon; and Brussels, Belgium
Purpose: Vagus nerve stimulation (VNS) is an established treatment modality for patients with medically refractory epilepsy. The purpose of this study was to prospectively evaluate the efficacy of VNS in a consecutive cohort of children implanted over a two years period at a single Medical Center in Lebanon. Method: Children with refractory epilepsy not candidates for epilepsy surgery and implanted with a VNS were prospectively evaluated. All children had a full evaluation, including CCTV/EEG monitoring, epilepsy protocol MRI, and metabolic and genetic testing when indicated. The responder rate (>50% reduction in seizure frequency) was assessed at 6, 12 and 18 months following implantation. In addition, the quality of life and usefulness of the magnet was assessed. Result: 40 children (range; 6 months18 years) were implanted. The responder rates were 50%, 63% and 67$ at 6, 12 and 18 months following implantation, respectively. In addition, 49% of children had amelioration in seizure severity, including shorter seizure duration in 30% and shorter post-ictal state in 26%. 56% of children had an improvement in the quality of life with an improvement in alertness and in the level of social interactions. The magnet was reported to be useful by 47% and the number of AEDs was reduced in 13% of those children. Conclusion: VNS is a good treatment option for children with refractory epilepsy when conventional therapy fails. Prospective studies are needed to better delineate the characteristics of children most likely to benefit from VNS implantation. 18% of studied cases. These cases responded to the second regimen course of ACTH injections. Conclusion: The use of ACTH in our new regimen for refractory seizures - other than infantile spasms- over 6 weeks will give the following advantages over the other anti-epileptic drugs: 1- rapid response - within 2 weeks - 2- short duration of management - within 6 weeks- 3- less Side -Effects- almost tolerable 4- after 6 months, few cases showed recurrence with the need of new 6 weeks course 5- parents are more satisfied with the short course treatment and the rapid response 5.
p580 CONTINUOUS INTERICTAL EPILEPTIFORM ACTIVITY AND ITS EFFECT ON COGNITION AND BEHAVIOR OF CHILDREN I. S. Ivanov, I. Pacheva, I. Sotkova, A. Petkova, P. Dimova, T. Markova, I. Ivanova, and E. Timova Plovdiv Medical University Hospital Sv. Georgi, Plovdiv, Bulgaria
Purpose: To investigate epilepsy, cognition and behavior in pediatric patients with continuous interictal epileptiform activity (CIEA) and find prognostic factors. Method: Among 577 pediatric patients with epilepsy 29 (5.03%) with CIEA were found. Six of them were excluded because of IQ/DQ <50%. The remaining 23 children (13 male) were thoroughly investigated. Result: Epilepsy was partial in 22 of the 23 patients (symptomatic in 12, cryptogenic- 5, idiopathic- 5). CIEA was diagnosed at mean age 6y 11mo. CIEA was focal in all infants, mostly temporal, unilateral or bilateral, awake and/or in sleep. Diagnosis of CIEA was associated with clinical findings in 21 patients: worsening of seizures (10 patients), worsening of language (14 patients), visual-spatial perception (11), fine motor tasks (12), vigilance (10), attention (13), hyperactivity (5), aggression (2), and other behavioral changes (5). AED, mostly VPA, BDZ and LEV, mainly in combinations of 2 (8 patients) or 3 (10), and CS in 2 patients, abolished CIEA in 14 cases. Improvement of cognition and behavior after adequate treatment was observed in 9 patients, 8 of them with improved seizures and 6 - with abolished CIEA. Unfavorable cognitive/behavioral prognosis in patients with CIEA was associated with perinatal and early infantile etiology, early onset of epilepsy (mean 3y 4mo, range 6mo7y 9mo), early diagnosis of CIEA (mean 2y 5mo, range 2y 5mo8y 7mo), secondary generalized seizures and epileptic status. Conclusion: CIEA is an alarming symptom in partial epilepsies with unfavorable effect on cognition and behavior, especially in early onset symptomatic epilepsies.
p579 A SHORT COURSE OF ACTH REGIMEN FOR TREATING REFRACTORY CHILDHOOD SEIZURES H. H. Abdeldayem Faculty of Medicine, Alexandria University, Egypt
Purpose: Childhood seizures that are refractory to conventional antiepileptic drugs (polytherapy) are distressing to physicians and parents. Adrenocorticotropic hormone (ACTH) injection (IM) has been suggested to be used for treating of theses refractory epilepsy in young children in a short course regimen (6 weeks). Subjects: Young infants and children: from 6 months age up to 4 years age. Inclusion criteria: 1- Refractory epilepsy with the use of at least 2 anti-epileptic drugs, 2- Cases with generalized tonicclonic epilepsy, myoclonic epilepsy, tonic, atonic or mixed epilepsy. Method: 6-weeks of ACTH treatment is followed by 6 months follow up thereafter. The study will enroll male and female children up to age of 4 years old with refractory epilepsy. Patients will receive ACTH (Synactan IM* Novartis) in dosage of 1 mg every alternate daily for 4 doses then 0.5 mg every alternate daily dosage for 4 doses then gradual decrease by 0.1 mg on alternate daily dosage for 4 doses per each dose (0.4mg, 0.3 mg, 0.2 mg, 0.1mg respectively). after 2 weeks, ACTH should be topped due to non tolerable side effects or failure of good response as regard fits control NB., EEG recording are performed before and after full ACTH regimen treatment. Result: ACTH was used by IM injection in 60 epileptic children using unsuccessfully 2 or more antiepileptic drugs. After 2 weeks of treatment 92% of cases showed improvement (less number of fits). After 6 weeks of treatment 89% of cases showed full remission. Minor Side effects (tolerable) as cushinoid faces (81%), irritability (12%) and gum blue pigmentation (14%). However, only 2 cases showed marked hypertension up to hospital admission. After 6 months, recurrence of fits occurred in
p581 PHOTOSENSITIVITY AT DIFFERENT FORMS OF EPILEPSY AND THERAPY FEATURES I. Schederkina*, and V. Karlov *Morozovskay Children Hospital, Moscow, Russian Federation; and Moscow State of Medicine and Dentistry University, Moscow, Russian Federation
Purpose: Photoparoxysmal reaction (PPR) is evaluated as generalized epileptiform activity spike- and polyspike-slow wave, occurring under rhythmic photostimulation and may be registered in different forms of epilepsy. Aim: to evaluate frequency of PPR among children with epilepsy, effect of different anticonvulsants on PPR. Methods: Clinical, electroencephalography, video-EEG sleep monitoring. Results: 116 children with different forms of epilepsy and PPR in EEG (68 boys and 48 girls) were observed. Forms of epilepsy were registered:
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idiopathic generalized -24%, juvenile myoclonic and cryptogenic focal 20.6% each, childhood and juvenile absence -8.6% each, Jeavans syndrome and symptomatic focal -5.1% each, occipital -3.4%, atypical rolandic and complex febrile seizures - 1.7% each. In 22.4% of cases PPR was registered at onset of epileptic seizures, 60% - during observetion, 3.5% - during anticonvulsant dose decrease, 13.7% - after cessation of anticonvulsant therapy. PPR was registered isolated in 22% of cases, was combined with generalized epileptiform activity -74%, frontal and temporoparietal -28% each, occipital -18%. Seizure types were: tonic-clonic -38%, myoclonic -29.3%, absence -22.4%, secondary generalized and complex focal -20.6% each. One third of children had a combination of types of seizure. In 75.8% clinic-encephalographic remission with monotherapy: valproates -52.2%, topiramate -18%, keppra -12.5%, ethosuximid - 5.6%, carbamazepin, trileptal -4.5%. In 24.1% was duotherapy: valproate+keppra -37.9%, valproate+topiramate -24%, valproate+ethosuximid -21%. Conclusion: Idiopathic generalized forms of epilepsy prevailed among children with PPR, one third of cases showed combination of seizure types. The most effective in monotherapy: valproates, topiramate, keppra. 100% efficiency for duotherapy: valproates with keppra, ethosuximid and topiramate.
*Moscow State of Medicine and Dentistry University, Moscow, Russian Federation; and Russian Cardiology Research and Production Complex, Moscow, Russian Federation
Purpose: To define the biological meaning of cerebral attacks. Method: First block. We investigated 52 patients with attacks, whose diagnoses have not been determined after the patients were examined by a cardiologist and neurologist. EEG sleep monitoring, EEG after sleep deprivation and the long passive orthostatic probe were used. Second block. We studied mechanisms of paroxysmality in patients of with epilepsy (E), panic attacks (PA) and a combination of epilepsy and panic attacks (E+), 30 patients in each group. The quality of autonomic regulation was studied via the registration of skin sympathetic response (SSR) and comparing this data with the EEG. Third study block. We studied 10 epileptic men with recurrent GTC seizures and alternative dysphoria. Result: First Block. As a result, 47 out of 52 patients (90.3%) were reported to have definite type of attacks. An interictal EEG pattern that reflects cerebral mechanisms common to different seizures was established. Second block. One of the main results is compensatory strain of the homeostatic stabilizing mechanism under a loading trial. MMPI showed full accordance with clinical data: the seizure serves as a factor eliminating of dysphoria. Conclusion: An initial defect on any systemic level stimulates homeostatic compensatory mechanisms. Under the influence of certain endogenous or exogenous factors, the homeostatic status can reach the critical level (extreme strain, overstrain). The biological essence of attack (seizure) is an acute breakdown of the overstrained homeostatic mechanism that mobilizes vital resources and leads to the re-compensation of homeostasis.
p582 COGNITIVE FUNCTION IN CHILDHOOD EPILEPSY-A SINGLE CENTER STUDY J. Park*, M. Yum*, H. Choi*, T. Ko*, and H. W. Kim *Asan Medical Center, Seoul, Korea; and Asan Medical Center, Seoul,
Purpose: Epilepsy is significantly associated with cognitive function. Many factors such as the etiology of epilepsy, onset age, antiepileptic drugs, can affect the cognition of the children with epilepsy. The aims of this study were to describe the cognitive performance in children with epilepsy and to determine frequency of cognitive impairment, and epilepsy-related factors correlating with cognitive impairment in a single tertiary center in Korea. Method: From January 2006 to March 2011, 322 children who were diagnosed with epilepsy were retrospectively enrolled. Korean Education Development Institute-Wechsler Intelligence scale for Children (KEDIWISC) was used to measure the cognitive function. Epilepsy-related factors (onset age, etiology, seizure type, frequency of seizure, antiepileptic drug medication) were analyzed to test the association with the level of cognition. v2 test or Fisher's exact T-test, logistic regression were used for statistical analysis. Result: Cognitive function was considered within normal in 146 (45.3%), borderline, in 18 (5.6%), mild mental retardation (MR) in 47 (14.6%), more severe MR in 111 (34.5%). 176 of 322 (54.7%) had subnormal intelligence. Early onset (<5 yr), symptomatic etiology, frequent seizure at the time of test, the number of antiepileptic drugs, the history of epileptic encephalopathy were each strongly associated with low level of cognitive function (p<0.05). The abnormal EEG finding has no association with the subnormal IQ (p>0.05) in this study. Conclusion: Epilepsy is inseparably linked to cognitive function. Explanations for these associations include the impact of the underlying structural/metabolic lesions, the effects of seizures and antiepileptic drugs, as potential mechanisms.
p584 GRANULE CELL DISPERSION IS ASSOCIATED WITH MORE SEVERE NEURONAL LOSS IN MESIAL TEMPORAL LOBE EPILEPSY WITH MESIAL TEMPORAL SCLEROSIS L. O. S. F. Caboclo*, R. S. D. C. Neves*, A. P. Jardim*, R. S. Centeno*, C. L. P. Lancellotti, C. A. Scorza*, E. Cavalheiro, and E. M. T. Yacubian* *Universidade Federal de Sao Paulo, Sao Paulo, Brazil; Santa Casa de Sao Paulo, Sao Paulo, Brazil; and UNIFESP, Sao Paulo, Brazil
Purpose: To analyze retrospectively a series of patients with mesial temporal lobe epilepsy (MTLE) and mesial temporal sclerosis (MTS) and to investigate the possible association of granule cell dispersion (GCD) with clinical data, patterns of MTS and surgical prognosis. Method: Sixty-six patients with medically refractory MTLE and unilateral MTS were included in the study. All patients were submitted to anterior temporal lobectomy. Tissue obtained in surgery, as well as thirteen control specimens, was studied. Quantitative neuropathological evaluation was performed on NeuN-stained hippocampal sections. MTS types were defined according to criteria established by Blumcke et al. (Acta Neuropathol 2007; 113: 235244). GCD was considered present when: (a) the width of the granule cell layer (GCL), assessed in the straight parts of the layer, was wider than 120 lm; (b) granule cells did not remain in close opposition to one another; and (c) the normal clear boundary between the molecular layer and the GCL was not maintained (El Bahh B et al. Epilepsia 1999; 40: 13931401). Result: GCD was present in 45.5% of cases. We found no correlation between clinical variables and GCD. Except for MTS type 2 (CA1 sclerosis, found in four patients without GCD and no patients with GCD),

p583 WHAT IS AN ATTACK (SEIZURE)? V. Karlov*, V. Gnezdizky*, and A. Pevzner
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no-GCD and GCD groups did not differ with respect to the types of MTS. More severe neuronal loss was found in patients with GCD. Surgical outcome was similar in both groups. Conclusion: GCD was associated with more severe hippocampal neuronal loss, but was not a predictor of surgical outcome. respectively. The plant extracts also showed protection against seizures induced cognitive impairment, oxidative stress and normalized the cholinesterase activity. Curcumin (300 mg/kg, p.o.) protected against kainic acid induced seizures and oxidative stress. Pre-treatment with curcumin for 21 days prevented the cognitive impairment induced by AEDs (phenytoin, phenobarbitone and carbamezepine). Single dose administration of curcumin potentiated the anti-epileptic effect of valproate, phenytoin, phenobarbitone and carbamazepine in experimental models of seizures, without altering serum levels of these AEDs. Conclusion: The protective effect of the plant extracts against seizures and seizure-induced cognitive impairment may be due to their anti-oxidant potential. The findings suggest their potential as an adjuvant to antiepileptic drugs.
p585 WHAT IS THE ROLE OF NEUROMEDIN N DURING SEIZURES? K. Maes, A. Van Eeckhaut, Y. Michotte, and I. Smolders Vrije Universiteit Brussel, Brussels, Belgium
Purpose: Neuropeptides play an important role when the central nervous system is challenged, such as during epileptic seizures. In order to obtain better insights in the peptidergic effects involved in limbic epilepsy, we monitor the concentration dynamics of some neuropeptides in the rat hippocampus during seizures. Furthermore, we aim to unravel the modulatory effects of the peptides on the excitability of the brain. This can lead to the identification of innovative peptidergic targets for new anti-epileptic drugs. In this study we focus on neuromedin N, because its role in epilepsy is elusive. Method: During a microdialysis experiment, neuromedin N content is measured in the rat hippocampus before, during and after pilocarpineinduced limbic seizures using nano liquid chromatography-electrospray ionisation-tandem mass spectrometry (nano LC-ESI-MS/MS). In ongoing experiments, the possible anticonvulsive effects of neuromedin N are investigated in rat and mouse models for partial seizures with secondary generalization. Result: The concentration of neuromedin N in rat basal hippocampal dialysates is found to be near the limit of detection of the method (1 pM). Therefore, further optimisation of the microdialysis, LC and MS/MS parameters is necessary to allow more sensitive and accurate measurements. During seizures we observe a 40-fold increase in the concentration of neuromedin N, which returns to baseline at the end of the experiment. Conclusion: These preliminary results show that the release of neuromedin N is increased in the rat hippocampus during seizures. Study of the possible anticonvulsive effects of neuromedin N is part of ongoing research.
p587 ELECTROPHYSIOLOGICAL RESPONSES TO VAGUS NERVE STIMULATION IN RATS L. Mollet, R. Raedt, J. Delbeke, R. El Tahry, V. De Herdt, A. Meurs, W. Wadman, K. Vonck, and P. A. J. M. Boon Neurology, Neuroscience, Ghent, Belgium
Purpose: Vagus nerve stimulation (VNS) for refractory epilepsy requires optimization of stimulation parameters to improve outcome. VNS exerts its effect by activating afferent, fast-conducting fibers. There is however a clear need for an objective parameter reflecting effective stimulation. We recorded electrophysiological responses to stimulation of the vagus nerve. Method: Rats were implanted with a stimulation electrode around the left cervical vagus nerve. Recordings were made using point electrodes placed on the vagus nerve rostral to the stimulating cathode. The vagus nerve was stimulated under anesthesia with a biphasic pulse (5ls/phase). Result: The electrophysiological response consisted of an early and a late component, identified as respectively an afferent compound action potential (CAP) and a far field potential of the larynx motor evoked potential (LMEP), with a conduction velocity of respectively 32.52.5m/ s and 33.31.3m/s. The I50% for the CAP and LMEP (respectively 1.90.3mA and 1.60.1mA) were not significantly different. Mean latency for the CAP and LMEP at 1.30.3mm rostral to the stimulating cathode, were 0.40.1ms and 2.00.2ms respectively. At 3.10.6mm rostral to the stimulating cathode, a difference in response latency was measured for the CAP, but not for the LMEP. Conclusion: Short biphasic pulses with an intensity of 1.52.5mA activate fast-conducting vagal fibers. Our set-up can be used to evaluate the effects of different stimulation parameters at the level of the cervical vagus nerve in epilepsy models.
p586 INDIAN HERBAL DRUGS IN EXPERIMENTAL MODELS OF EPILEPSY Y. K. Gupta, K. H. Reeta, M. Pahuja, and J. Mehla All India Institute of Medical Sciences, New Delhi, India
Purpose: Indian medicinal plants used in CNS disorders, as nervine tonic in traditional system of medicine and also have significant antioxidant activity was evaluated against experimental models of seizures and seizure induced cognitive impairment. Method: Seizures were produced by acute pentylentetrazole (PTZ), maximal electroshock (MES), kainic acid induced seizures and PTZinduced kindling in rats. Cognitive function was assessed by elevated plus maze and passive avoidance tests. Oxidative stress markers (MDA and GSH) and cholinesterase (AChE and BChE) activity were also evaluated. Interaction profile of the plant extracts with standard antiepileptic drugs (AEDs) were also studied. Result: Hydroalcoholic extracts of Acorus calamus (200 mg/kg, p.o), Anacyclus pyrethrum (500 mg/kg, p.o), Benincasa hispida (1000 mg/kg, p.o), Orchis mascula (1000 mg/kg, p.o) and Zizyphus jujuba (1000 mg/ kg, p.o) showed protection against generalized tonic-clonic seizures (GTCS) and hind-limb extension (HLE) in PTZ and MES models,
p588 CONVULSANT ACTIVITY OF PILOCARPINE IN MICE IS LIMITED BY MULTIDRUG-TRANSPORTERS AT THE BLOOD-BRAIN BARRIER M. Bankstahl, K. Rmermann, J. P. Bankstahl, and W. Lscher University of Veterinary Medicine Hannover, Hannover, Germany
Purpose: Pilocarpine is widely used to induce status epilepticus in rodents resulting in development of chronic epilepsy. Aim of this study was to evaluate the influence of the multidrug-transporters P-glycoprotein (Pgp, Mdr1) and breast cancer resistance protein (Bcrp) on brain uptake and convulsant activity of pilocarpine. Method: Cumulative dose of pilocarpine needed to induce status epilepticus in wild type (WT, FVB/N) and Mdr1a/b(-/-) mice of either gender was determined. The pharmacokinetic profile following a single
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pilocarpine injection in WT mice was recorded over 120 minutes. Finally, brain uptake of pilocarpine was compared in Mdr1a/b(-/-), untreated WT mice and WT mice pretreated with the dual Pgp/Bcrpinhibitor tariquidar (15 mg/kg). Transport of pilocarpine by Pgp and/or Bcrp1 was further investigated in in-vitro concentration equilibrium transport assays using Mdr1a- and Bcrp1-overexpressing cells. Result: In Mdr1a/b(-/-) mice, a significantly lower dose of pilocarpine (297 68 mg/kg) was sufficient to induce status epilepticus compared to 453 154 mg/kg in WT mice. This difference was gender-independent. Maximal pilocarpine levels in brain tissue were reached after about 20 minutes. Plasma elimination half-life was 35 minutes. Pilocarpine brain uptake was only slightly increased in Mdr1a/b(-/-) mice compared to WT mice, whereas tariquidar-treated animals displayed a marked increase (~80%) in pilocarpine brain uptake. Our in-vitro studies showed effective transport of pilocarpine by Bcrp and, less pronounced, by Pgp. Conclusion: Our data reveal that Bcrp and, to a lesser extent, Pgp play a role in limiting the brain entry of pilocarpine and hereby influence its convulsant properties. Purpose: Neuropeptide Y (NPY) and leptin are the two peptides involved in feeding behaviour, seizure, cardiovascular regulation and stress. NPY expression has been shown to enhance in low diet rats whereas plasma leptin concentration decreased. Overexpression of NPY by recurrent epileptic seizures particularly in hippocampus could be considered as a protective mechanism against to epileptic activity (Vezzani A and Gnther S. Neuropeptides 2004; 38:245252). Although NPY has been shown to suppress absence seizures in genetic absence epilepsy rats from Strasbourg (GAERS), GAERS show resistance to electrical kindling. This study aimed to compare the main metabolic parameters of GAERS and Wistar animals as well as plasma leptin and NPY levels related to involvement in the resistance mechanism of GAERS to kindling. Method: Adult male GAERS (n=6) and control Wistar rats (n=5) were used. Following one week acclimation in the metabolic cages, daily body weight, food and water intake, urea and feces amounts of the animals were recorded for one week and blood samples were stored until the measurement of leptin and NPY levels. Result: Mean body weight, food intake and feces amount of the GAERS were lower than Wistar rats (22%, 26.3%, and 13.3% respectively) whereas water intake and urea measurement results not. The NPY and leptin levels have not been measured yet. Conclusion: These results can be indicative for different leptin and NPY levels. We also plan to analyze protein expression of NPY in the hippocampus of the GAERS and Wistar rats in the future.
p589 RUTIN REDUCES NEUROINFLAMMATION AND NEURONAL DEGENERATION IN THE RAT BRAIN AFTER KAINIC ACID-INDUCED STATUS EPILEPTICUS M. Golechha*, U. Chaudhry*, D. Saluja*, and D. Arya *Dr. B R Ambedkar Center for Biomedical Research, New Delhi, India; and All India Institute of Medical Sciences, New Delhi, India
Purpose: This study was undertaken to investigate the neuroprotective effects of rutin (vitamin P) on kainic acid (KA)-induced status epipeticus in rats. Oxidative stress and inflammation is an important event, play a crucial role in neurodegenerative diseases. Rutin has been shown to have antioxidant and anti-inflammatory actions, and thus was tested for its beneficial effects using KA-induced status epipeticus in rats. Method: Male wistar rats were treated with rutin at doses of 25, 50 and 100 mg/kg, i.p. for 7 successive days before KA administration. Rats were observed for behavioral changes and incidence and latency of convulsions. The effect of rutin on KA-induced cell injury was also investigated on several cellular pathways including neuronal plasticity (RhoA), neurodegeneration (Caspase-3), and inflammation (COX-2) in PC12 cells and microglial BV-2 cells. Result: Pretreatment with rutin (50 and 100 mg/kg, i.p.) significantly increased the latency of seizures as compared to the vehicle-treated KA group. Rutin was effective to protect PC12 cells and BV-2 cells from KA-injury in a dose-dependent manner. It decreased the release of Ca2+, reactive oxygen species, and MDA from PC12 cells. Western blot analysis revealed that rutin significantly reduced ERK1/2, p38 mitogen-activated protein kinases, Caspase-3, and COX-2 expression in both cells and RhoA expression in BV-2 cells. Furthermore, rutin was able to reduce PGE2 production from both cells under KA-stimulation. Conclusion: Taken together, it suggests that rutin could protect KAinduced brain injury through anti-inflammatory and partially anti-oxidative mechanisms.
p591 EFFECT OF ANACYCLUS PYRETHRUM ON PENTYLENETETRAZOLE-INDUCED KINDLING, COGNITION, OXIDATIVE STRESS AND RHO-KINASE II EXPRESSION IN MICE M. Pahuja, K. H. Reeta, M. Tripathi, and Y. K. Gupta All India Institute of Medical Sciences, New Delhi, India
Purpose: Anacyclus pyrethrum a perennial, procumbent plant has been reported to exhibit anticonvulsant activity. In the present study, the effect of hydroalcoholic extract of A. Pyrethrum root (HEAP) on pentylenetetrazole (PTZ) induced kindling, spatial memory, oxidative stress and rho kinase II was assessed. Method: Male albino mice (2530 g) were used in the study. PTZ-35 mg/kg, i.p was administered to induce kindling and PTZ-70 mg/kg, i.p challenge was given, 7 days post kindling. HEAP (100, 250 and 500 mg/kg, orally) were administered for 35 days. Spatial memory was assessed using Morris water maze. The oxidative stress parameters were also assessed by estimation of malondialdehyde (MDA) and reduced glutathione (GSH). Rho kinase II expression was studied by western blotting. Result: HEAP pre treatment showed a significant dose-dependent increase in the myoclonic jerk latency and delay in development of kindling, which is comparable to that of valproate treated group. 30% and 20% mortality was observed in PTZ group and HEAP 100 mg/kg group, respectively. Whereas, no mortality was observed at higher doses (250 and 500 mg/kg). Pre-treatment with HEAP increased the number of platform crossings on water maze test, as opposed to the PTZ group, thus showing protection against memory deficit. HEAP pre treatment also attenuated the oxidative stress induced by kindling. PTZ increased ROCK II expression whereas, HEAP pre treatment attenuated the increase in ROCK II expression. Conclusion: HEAP pre treatment showed antiepileptic effect in PTZ induced kindling in mice and also protected cognitive impairment, oxidative stress and showed rho kinase II inhibitory activity in PTZ kindled mice.
p590 DOES FEEDING BEHAVIOUR OF GENETIC ABSENCE EPILEPSY RATS DIFFER FROM CONTROL WISTAR RATS? M. Gulcebi Idriz Oglu*, S. Ketenci*, T. Karamahmutoglu*, D. Akin, and F. Onat* *Marmara University School of Medicine, Istanbul, Turkey; and Istanbul Bilim University School of Medicine, Istanbul, Turkey
172 Abstracts

p592 THE PRESENCE OF THE CAV3.2 R1584P MUTATION IS ASSOCIATED WITH RESISTANCE TO KINDLING INDUCED CHANGE IN THE TRN NEURON FIRING PATTERN N. Carcak*, T. Zheng, N. C. Jones, L. Van Raay, K. Powell, F. Onat, and T. J. OBrien *Istanbul University Faculty of Pharmacy, Istanbul, Turkey; University of Melbourne, Melbourne, Australia; and Marmara Univeristy School of Medicine, Istanbul, Turkey
Purpose: Genetic Absence Epilepsy Rats from Strasbourg (GAERS, a well validated model of idiopathic generalized epilepsy, carry a gain-offunction mutation (R1584P) in the T-type calcium channel, Cav3.2, which contributes the epileptic phenotype in F2 progenies derived from GAERS and non-epileptic control (NEC) rats. GAERS are resistant to the development of secondarily generalized seizures with amygdala kindling. We investigated whether the Cav3.2 (R1584P) mutation influences kindling resistance and the effect of kindling on neuronal firing in the reticular nucleus of the thalamus (TRN). Method: Double crossed (GAERS NEC) F2 generation rats homozygous (m/m) or null (+/+) for the Cav3.2 (R1584P) mutation were kindled twice daily to a maximum of 30 stimulations. Thereafter extracellular single neuronal recordings from TRN were performed in vivo under neuralept anaesthesia. Result: The rate of behavioural seizure progression was not different between the genotypes (p>0.05). However, the rats null for the mutation (+/+) appear to have longer and faster progression of the electrographic seizure durations during kindling compared to those homozygous for the mutation (m/m) (p= 0.039). The TRN firing frequency in rats null for the Cav3.2 (R1584P) mutation was significantly lower (+/+: 5.11) than rats homozygous for the Cav3.2 (R1584P) mutation (m/m: 11.75)(p=0.03). A decrease in firing frequency is correlated with an increase in the amount of burst firing (R2=0.52). Conclusion: These results indicate changes in neuronal firing patterns in the thalamus in the progression of amygdala kindling, and support a role for the Cav3.2 R1584P mutation in the kindling resistance of GAERS.
doses. Kainic acid induced only epileptic automatisms scratching in 12and wet dog shakes and scratching in 25-day-old rats. CGP46381 again was more effective in 12-day-old rats - it increased the intensity and frequency of automatisms in a dose-dependent manner - whereas effects in 25-day-old animals were mild. Conclusion: An antagonist of GABAB receptors was active in 12-dayold rats in both models induced by different mechanisms antagonism of GABAA receptors (pentetrazol) and antagonism of kainic acid glutamate receptors. There was no effect on pentetrazol action in 25-day-old rats and a mild effect on kainic acid-induced automatisms. The role of GABAB receptors is age- as well as model-dependent. Supported by a grant No. P304/10/1274 of the Grant Agency of the Czech Republic
p594 THE ANTIDEPRESSANTS CITALOPRAM AND REBOXETINE REDUCE SEIZURE FREQUENCY IN CHRONIC EPILEPTIC RATS R. Clinckers, K. Vermoesen, A. Massie, and I. Smolders Vrije Universiteit Brussel, Brussels, Belgium
Purpose: Antidepressants have long been considered to possess proconvulsant properties. This assumption however remains controversial since anticonvulsant effects have been attributed to certain antidepressants. The present study was designed to determine the seizure liability of citalopram and reboxetine in the kainic acid-induced post-status epilepticus model for temporal lobe epilepsy. Method: Two months after the induction of status epilepticus, chronic epileptic rats (n=16) were video-EEG monitored during 7 consecutive weeks. Weeks 1, 3, 5 and 7 served as sham weeks during which the rats received intraperitoneal saline injections for 4 consecutive days, followed by a 3-day sham washout period during which no injections were given. During weeks 2, 4 and 6 rats received intraperitoneal injections with either citalopram (5, 10 and 15 mg/kg, once daily, n=8) or reboxetine (10, 20 and 30 mg/kg, twice daily, n=8) for 4 days, again followed by a washout period of 3 days. Drugs were administered in a randomly assigned fixed-dose regimen per week. Each rat served as its own control. The drug doses were selected based on the doses reported to have antidepressant effects in rats. Result: Both antidepressants significantly decreased spontaneous seizure frequency (15 mg/kg citalopram: 31% decrease; 20 mg/kg reboxetine: 44% decrease; 30 mg/kg reboxetine: 39% decrease). Citalopram and reboxetine had no effect on mean seizure severity and seizure duration in any of the doses tested. Conclusion: In general we conclude that antidepressant doses of citalopram and reboxetine have an anticonvulsant effect on spontaneous seizures in the kainic acid-induced post-status epilepticus rat model.
p593 AN ANTAGONIST OF GABAB RECEPTORS EXHIBITS PROCONVULSANT ACTION IN BOTH AGE- AND MODEL-DEPENDENT MANNER P. Mare Institute of Physiology, Academy of Science, Prague 4, Czech Republic
Purpose: Agonists of GABAB receptors exhibit mixed anti- and proconvulsant action. Anticonvulsant action is more marked at early stages of development, proconvulsant action of antagonist can be expected in immature rats. Method: Rat pups 12 and 25 days old were pretreated with an antagonist of GABAB receptors CGP46381 (130 mg/kg intraperitoneally) and 30 min later pentetrazol (60 mg/kg subcutaneously) or kainic acid (intraperitoneally - 4 mg/kg in 12- and 6 mg/kg in 25-day-old rats) was injected. Animals were observed in isolation for 30 min and seizures were registered. Result: Pentetrazol in the dose of 60 mg/kg led exceptionally to convulsive seizures. CGP46381 potentiated the convulsant effect in 12- but not 25-day-old rats. Significant changes were found in the incidence and severity of seizures in the younger group after the 10- and 30-mg/kg
p595 ANTIEPILEPTIC EFFECT OF TIANEPTINE IN PENTYLENETETRAZOLE INDUCED SEIZURES IN RATS: POSSIBLE ROLE OF NMDA RECEPTOR R. Kh, P. Prabhakar, J. Mehla, and Y. K. Gupta All India Institute of Medical Sciences, New Delhi, India
Purpose: Depression is a common morbidity in epileptic patients. Adversely, some antidepressants are known to reduce seizure threshold. Tianeptine, an antidepressant drug, has recently been shown to have antiseizure effect in experimental models. The present study examined the effect of tianeptine on seizures and its interaction with N-methyl-Daspartate (NMDA) receptor. Method: Male Wistar rats (175225 g) were used. In pentylenetetrazole (PTZ) induced seizure, animals were divided into five groups. The first group received PTZ, 60 mg/kg; i.p. In the second, third and fourth groups,
173 Abstracts
tianeptine was administered in three doses of 20, 40 and 80 mg/kg, p.o., 60 min before PTZ injection. In the fifth group, valproate, 300 mg/kg, i.p. was administered as the standard control. In another set of experiments, tianeptine was administered with NMDA 120 mg/kg; i.p., NMDA antagonist (MK-801, 1 mg/kg; s.c.) with and without PTZ chemoconvulsant challenge. Behavioural parameters were assessed before and after seizure induction by using a battery of tests. Result: Tianeptine exhibited dose-dependent protection against PTZ induced seizures. No generalised tonic clonic seizures were observed with tianeptine, 80 mg/kg. Tianeptine also showed complete protection against NMDA induced seizures. Co-administration of tianeptine with MK-801 potentiated the anti-convulsant effect of tianeptine suggesting involvement of NMDA receptor. Impairment of learning and memory caused by seizures was reversed by tianeptine. Conclusion: The protective effect of tianeptine against PTZ and NMDA-induced seizures as well as reversal of cognitive impairment suggests the potential of tianeptine in epileptic patients with depression.
*Lab#314, HEJ Research Institute of Chemistry, ICCBS, Karachi, Pakistan; and Dr. Panjwani Centre for Molecular Medicine and Drug Research, Karachi, Pakistan
Purpose: Epilepsy is a neurological disorder manifested by recurrent seizures, resulting from synchronized discharges of neurons in brain, affecting at least 1% of the world population. The antiepileptic drugs available in market have significant side effects and resistance. Therefore, it is logical to search for better and safer newer antiepileptic drugs. In addition, c-Fos and BDNF are the underlining cellular and molecular factors reported to be tightly coupled with epileptogenesis, therefore we have focused on these two markers. Method: Keeping these facts in mind, our group also focused on synthesizing a tryptamine derivative, HLL-6, with potential anti-epileptic activity and minimal adverse effects by the help of our chemist collaborators. Pentylenetetrazole (PTZ) was used to induce kindling in mice in our study (n = 12). The immunohistochemical analysis of c-Fos and BDNF proteins in the cryo-sectioned brain slices of both the kindled and normal animals was performed. The image processing program ImageJ (NIH, USA) was used to analyze the images. Data were obtained from two sections per mouse and presented as means SEM. Result: Our results demonstrated that HHL-6 not only possesses potent anticonvulsant and anti-epileptic activity in the PTZ-induced acute seizure and chemical kindling model of epilepsy but also shows a marked reduction in the over-expression of c-Fos and BDNF proteins seen in the control kindled group. Conclusion: Based on our results we suggest that the HHL-6 might be acting as an anti-epileptogenic by controlling the cellular expression of the factors that contribute in the development of epileptogenic plasticity in the CNS.
p596 SUCROSE PREFERENCE TEST REVEALS DEPRESSION-ASSOCIATED ANHEDONIC BEHAVIOUR IN EPILEPTIC MICE S. Klein, M. Bankstahl, J. P. Bankstahl, and W. Lscher University of Veterinary Medicine Hannover, Hannover, Germany
Purpose: Depression is a major co-morbidity in epilepsy patients but underlying mechanisms are poorly understood. Anhedonia, which is a characteristic symptom of depression in human patients, has been shown to occur also in chronically epileptic rats. This is the first study to investigate whether the sucrose preference test can reveal anhedonic behaviour in a mouse model of chronic epilepsy. Method: Female FVB/N mice were single housed. Baseline water uptake and preference of either sucrose (4%, group 1) or saccharin (0.1%, group 2) compared to water consumption was quantified. Subsequently, a status epilepticus was induced by fractionated i.p. administration of pilocarpine. At several time points during epileptogenesis (up to 8 weeks after status epilepticus) either sucrose or saccharin consumption compared to water was measured (further time points are under evaluation). Sham-treated animals served as controls. Additional groups of similarly treated rats were used as reference. Result: Baseline water uptake did not differ between groups. Absolute and relative sucrose or saccharin consumption in post-status-epilepticus mice was significantly decreased at all investigated time points. In epileptic rats, however, only absolute sucrose consumption was reproducibly decreased. Conclusion: Our data provide evidence that the sucrose preference test is suitable to measure anhedonia as an equivalent of epilepsy-associated depression-like behaviour in mice. We will use this test for further studying underlying mechanisms and possible treatments of the co-morbidity of epilepsy and depression in genetically modified mice.
p598 TARGETING EPILEPSY: MOLECULAR MARKERS OF EPILEPTOGENESIS AND ITS MODULATION BY ISOXYLITONES [E/Z ISOMERIC MIXTURE] S. U. Simjee*, M. N. Ashraf*, F. Shaheen*, A. Rahman, M. I. Choudhary, N. Kabir, S. U.A. Shah, N. Khan*, and S. Jamall *International Center for Chemical and Biological Sciences, Karachi, Pakistan; Karachi, Pakistan; International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan; and University of Karachi, Karachi, Pakistan
Purpose: An early immediate gene c-fos has been proposed as the gene responsible for turning on molecular events that might underlie the longterm neural changes occurring during kindling. We have evaluated the effects of novel anticonvulsant isomeric compound isoxylitones (E/Z) on the c-Fos expression in the brain samples of kindled mice. Method: Kindling was induced in NMRI mice by pentylenetetrazole (PTZ) until a seizure score of 45 was achieved. The c-Fos expression was quantified by immunohistochemistry and RT-PCR protocols. Result: Immunohistochemical and RT-PCR analysis revealed a marked increase in the expression of c-fos in the brain regions in case of PTZ-kindled control group compared to normal control. In comparison to PTZcontrol group, the isoxylitones (30 mg/kg)-treated group demonstrated significant reduction of c-Fos expression. However, low expression of cfos mRNA was only detected in the thalamus of the isoxylitone-treated brain samples. Conclusion: Based on these observations, we suggest that isoxylitones may have the capacity to control the seizure pattern by mechanism such as the suppression of c-Fos protein and mRNA levels in different regions of the brain. Further investigations to explore the mechanism of action of these compounds are under process.
p597 MODULATION OF C-FOS AND BDNF PROTEINS EXPRESSION IN PTZ-KINDLED MICE FOLLOWING THE TREATMENT WITH NOVEL ANTI-EPILEPTIC COMPOUND 2-ACETYL-3-(2-HEXANOYLAMIDOETHYL)-7-METHOXYINDOLE: AN IMMUNOHISTOCHEMICAL ANALYSIS S. M. Malhi*, H. Jawed*, F. Hanif, N. Ashraf*, S. Farhat*, B. Siddiqui*, S. Begum*, and S. U. Simjee*
174 Abstracts
p599 CENTRAL AND OBSTRUCTIVE APNEA AND CARDIAC ARRHYTHMIA DURING SEIZURES ALL PLAY ROLES IN SUDDEN DEATH IN A DRAVET SYNDROME MOUSE MODEL Y. Horigome*, M. Iizuka, I. Ogiwara, T. Shinba*, and Y. Takahashi* *National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan; Ibaraki Prefectural University of Health Sciences, Ami, Japan; and RIKEN Brain Science Institute, Wako, Japan
Purpose: Sudden unexpected death in epilepsy (SUDEP) is a tragic event to be avoided but the mechanisms still remain unclear. Patients with Dravet syndrome (DS) with SCN1A gene mutations show extremely high incidence of SUDEP. The DS mouse model harboring a heterozygous Scn1a mutation (R1407X; RX/+) also exhibits very high mortality rate, and 40% die before postnatal day (P) 90. To elucidate the mechanisms of SUDEP, we performed simultaneous recordings of respiration/ ECG/EEG in RX/+ mice. Method: The respiration during spontaneous seizures was monitored by whole-body plethysmograph in 31 RX/+ mice. Simultaneous ECG/EEG/ respiration recordings were also performed when feasible. Seizures were recorded in all the experiments by video. Preventive effects of mechanical ventilation and oxygen pretreatment against death were evaluated in pentylenetetrazol-induced seizures (150mg/kg i.p.) in RX/+ mice. Result: In younger pups (P1722, n=11), seizures with small jumps (popcorn seizures) clustered and they were not lethal. From P21, jumping seizures followed by tonic hindlimb extension appeared (n=10), resulting in sudden respiratory arrest and sudden death in four (P23, 24, 24, 86). In the other six mice, respiration resumed after 1242 sec apnea. Gasping was clearly observed after central apnea, indicating coexistence of upper airway obstruction. Various types of cardiac arrhythmia appeared during seizures, including profound bradyarrhythmia (7080% reduction of heart rate), ventricular tachycardia and torsade-like ST-T wave changes. Conclusion: The present study showed that ictal deaths were caused by sudden central and subsequent obstructive apnea after generalized jumping seizures. Cardiac arrhythmias might also be implicated in the mechanism. sides of dorsal hippocampus. Five weeks after, it was checked whether seizures were controlled or not, and then, brains were analyzed by immunohistochemistry using GFP, GAD, and Neu-N. Result: In EL, gNSCs transplanted group showed no seizure at all, whereas vehicle control showed seizures. GAD positive transplanted (GFP positive) neurons (NeuN positive) were observed more clearly in the GABAergic group, compared with those of neuron-induced group. Conclusion: Inhibitory differentiated gNCSs transplanted mice showed GAD positive cells more remarkably than those of nNCSs transplanted mice. In EL, the hippocamous and the parietal cortex may have a capacity for inhibitory neurons to control seizures.
p601 C-FOS EXPRESSION AFTER HIPPOCAMPAL DEEP BRAIN STIMULATION IN RATS J. Silva, M. Marques, F. Scorza, E. Cavalheiro, and A. Cukiert UNIFESP, Sao Paulo, Brazil
Purpose: Hippocampal deep brain stimulation (Hip-DBS) is a promising technique for treatment of patients with refractory temporal lobe epilepsy not amenable for conventional resective surgery. On the other hand, little is known about its effect on normal or pathological brain activity. We describe the expression of c-FOS after Hip-DBS in rats. Method: Six awaken male Wistar rats implanted bilaterally with neocortical and hippocampal electrodes and 2 control (non-stimulated) animals were studied. The animals were submitted to 1 hour or 6 hours of unilateral continuous hippocampal high frequency (130Hz) stimulation. Immunohistochemistry was employed to visualize c-fos distribution in different brain areas. Tissue sections were mounted on glass slides. The material was studied with a microscope using bright-field illumination. Result: c-FOS was significantly overexpressed bilaterally (although prevailing ipsilaterally) after unilateral Hip-DBS in regions comprising the hippocampus, pyriform gyrus, amygdala, olfactory nuclei, anterior nucleus of the thalamus and mammilary body, and less markedly over the cingulate cortex. No other thalamic or brain stem nuclei were shown to overexpress c-FOS. Conclusion: Unilateral Hip-DBS was able to affect all the basic relays of the limbic system and could potentially modulate that system bilaterally. This contrasts with recent findings showing that anterior nucleus stimulation led to very weak c-FOS activation of the hippocampus, suggesting that Hip-DBS might be a better target for limbic system neuromodulation. FAPESP, CInAPCe-FAPESP, CNPq and FAPESP/CNPq/ MCT-Instituto Nacional de Neurocincia Translacional.
p600 TRANSPLANTATION OF EMBRYONIC STEM CELLS TO DORSAL HIPPOCAMPUS OF EPILEPTIC MUTANT EL MICE Y. L. Murashima Tokyo Metropolitan University Graduateschool of Human Health Science, Tokyo, Japan
Purpose: Pluripotent embryonic stem (ES) cells differentiate into neurons in vitro. This is the key in the study of neurogenesis and in the generation of donor cells for neuronal transplantation. Cultured in astrocyteconditioned medium (ACM), colonies of undifferentiated mouse ES cells give rise to floating spheres of concentric stratiform structure with a periphery of neural stem cells: Neural Stem Spheres (NSS). Culturing the spheres on an adhesive substrate in ACM promotes neurogenesis. EL mice show secondary generalized seizures, which initiate at the parietal cortex and generalize through the hippocampus. The purpose of the present study was to examine how transplanted neural stem cells (NSCs) differentiate into inhibitory neurons and play a role of anti-epileptic effects in EL mice. Method: Neuron-induced NSCs (nNSCs), GABAergic neuron-induced NSCs (gNSCs) after 24hrs incubation from NSCs originated from NSS were used for the transplantation. 1 104 cells were transplanted to both

p602 HIGH FREQUENCY HIPPOCAMPAL DEEP BRAIN STIMULATION (HIP-DBS) DID NOT ENHANCE INFLAMMATORY MEDIATORS IN THE RAT HIPPOCAMPUS S. Perosa, J. Silva, F. Scorza, E. Cavalheiro, M. NaffahMazzacoratti, and A. Cukiert UNIFESP, Sao Paulo, Brazil
Purpose: There are clinical and experimental evidence that suggest that inflammatory mediators and processes could modulate epileptogenesis.
175 Abstracts
DBS has been increasingly used in the treatment of refractory epilepsy. In this study, we investigated if Hip-DBS influenced inflammatory mediators in the rat. Method: Six awaken male Wistar rats implanted bilaterally with neocortical and hippocampal electrodes and 2 control (non-stimulated) animals were studied. The animals were submitted to 1 hour or 6 hours of unilateral continuous hippocampal high frequency (130Hz) stimulation. Immunohistochemistry was employed to visualize antibradykinin B1 receptor, anti-bradykinin B2 receptor, TNF| and IL1| in the hippocampal formation. Tissue sections were mounted on glass slides. The material was studied with a microscope using bright-field illumination. Result: There was no difference in the expression of any of the studied inflammatory mediators in the hippocampus of the rat after Hip-DBS. Conclusion: The mechanisms through which Hip-DBS might lead to an anticonvulsant effect are poorly understood. This type of neuromodulation, which triggers intense c-FOS activation within the whole limbic system, did not cause overexpression of inflammatory mediators. Inflammatory pathways might not be involved in the cascades leading to seizure frequency reduction after Hip-DBS. FAPESP, CInAPCe-FAPESP, CNPq and FAPESP/CNPq/MCT-Instituto Nacional de Neurocincia Translacional.
p604 ARE ASTROCYTES INVOLVED IN THE EPILEPTOGENESIS?. THE EFFECTS OF THROMBOSPONDIN RECEPTOR BLOCKAGE IN A MODEL TEMPORAL LOBE EPILEPSY A. J. Ramos, A. Rossi, M. F. Angelo, A. Villarreal, J. Lukin, and A. G. Reines School of Medicine, University of Buenos Aires, Ciudad de Buenos Aires, Argentina
Purpose: Reactive astrocytes are known to secrete thrombospondins (TSP) that are specifically involved in the glutamatergic synaptogenesis. During the latency neuronal network reorganization is supposed to be the substrate for the epileptogenesis. In this study we evaluated if astrocytes and TSP are involved in the exacerbated neuronal plasticity that occurs during the latency period that precedes the final appearance of spontaneous recurrent seizures. Method: Using loss of function studies achieved by blocking the neuronal thrombospondin receptor alpha2delta1 with gabapentin (Gp) in rats exposed to the Lithium-pilocarpine model of temporal lobe epilepsy, we followed the changes in neuronal circuits and reactive gliosis. Adult male Wistar rats were treated with 3mEq/kg LiCl and 20h later with 30mg/kg pilocarpine (ip). 15 minutes after the onset of the status epilepticus (SE), they received 10mg/Kg diazepam. For the next 15 days animals received 400 mg/kg/day Gp or saline. In vitro, glio-neuronal hippocampal cultures were exposed to excitotoxic glutamate and subsequently to Gp (5, 25, 50 or 100 ug/ml) or vehicle. Result: During the latency, SE animals showed reactive gliosis, neuronal degeneration, ultrastructural alterations in synapses with atypical expression of synaptofisin (Syn) and increased level of plasticity marker PSA-NCAM in the hippocampus. Gp treatment reduced the alterations in Syn and PSA-NCAM but was unable to modify the neuronal loss and reactive gliosis. In glio-neuronal culture, Gp treatment partially prevented the dendritic loss caused by glutamate. Conclusion: The atypical synaptic morphology is probably related to the exacerbated neuronal plasticity and blockage of neuronal TSP receptor partially prevented this effect
p603 THE EFFECT OF HIGH FREQUENCY, POISSON DISTRIBUTED CORTICAL STIMULATION ON CORTICAL EXCITABILITY IN RATS I. Buffel*, A. Meurs*, R. Raedt, V. De Herdt*, R. El Tahry*, B. Van Nieuwenhuyse*, L. Mollet*, W. Wytse, K. Vonck*, and P. A. J. M. Boon* *University Ghent, Ghent, Belgium; Ghent University, Ghent, Belgium; and Swammerdam Institute of Life Sciences, Amsterdam, The Netherlands
Purpose: Neurostimulation is a promising treatment for patients with refractory focal epilepsy who are not amenable to resective surgery. We have evaluated the effect of high-frequency cortical stimulation on cortical excitability in the motor cortex model (CSM). In the CSM, a rampshaped pulse train with increasing intensity is delivered to the motor cortex. The threshold intensity for eliciting forelimb clonus is determined through behavioural observation, and used as a measure for cortical excitability. Method: Seven male Wistar rats were implanted with epidural electrodes over the motor cortex (AP-1mm; ML3mm). All rats underwent 1h of sham stimulation, cortical stimulation (Poisson pulse, 130Hz, PW100ls) with an intensity of 10lA, or cortical stimulation at 100lA below the baseline threshold intensity on alternating days. The threshold intensity needed to elicit forelimb clonus was determined before (mean of 4measurements at 20min intervals) and immediately, 1h, 2h and 24h after stimulation. Result: Sham stimulation did not alter the threshold to forelimb clonus. Therapeutic stimulation with an intensity of 100lA lower than baseline threshold (mean intensity 20522lA) significantly increased the threshold to forelimb clonus from 30522lA (before) to 34719 (immediately after), 33923 (1h), 32720 (2h) and 27721lA (24h) after stimulation (p<0.001). When stimulated at 10lA, the threshold increased from 30225lA to 31915lA, 31821lA, 31918 lA, 32132lA. Conclusion: High-frequency, Poisson-distributed cortical stimulation decreases cortical excitability at high intensities. This effect lasted 1h. Further studies are needed to determine whether this type of stimulation can become an effective alternative treatment for patients with focal neocortical epilepsy who are not amenable to surgery.
p605 IDENTIFICATION OF KINASE INHIBITORS THAT PROTECT AGAINST SEIZURES IN ZEBRAFISH AND RODENT MODELS OF EPILEPSY N. Aourz*, A. Serruys, J. N. Chabwine, P. B. Balegamire, T. Afrikanova, R. Edrada-Ebel, A. Grey, A. R. Kamuhabwa, L. Walrave*, R. Clinckers*, C. V. Esguerra, P. A. M. De Witte, I. J. Smolders*, and A. Crawford *Vrije Universiteit Brussel, Brussels, Belgium; Leuven, Belgium; Bukavu, Congo; Scotland, UK; and Dar es Salaam, Tanzania
Purpose: In view of the clinical need for new anti-epileptic drugs (AEDs) with novel modes of action, we used a zebrafish seizure model to screen the anticonvulant activity of medicinal plants used for traditional epilepsy treatment in the Congo, identifying 4 crude plant extracts that inhibited pentylenetetrazol (PTZ)-induced seizures in zebrafish larvae. Bioassay-guided fractionation of an anticonvulsant Fabaceae species identified an alkaloid with known kinase inhibitory activity***. This compound, a more potent and specific structural analog, and a structurally unrelated kinase inhibitor were analyzed in zebrafish and rodent seizure assays. ***For intellectual property reasons, the identity of the plant species, compounds and kinase target will first be revealed at the 10th European Congress on Epileptology in London.
176 Abstracts
Method: Locomotor activity of PTZ- and pilocarpine-treated zebrafish larvae was quantified by automated video tracking (Viewpoint). Seizures were induced in NMRI mice by corneal stimulation (6Hz, 0.2 ms rectangular pulse width, 3s duration) and in Wistar rats by intrahippocampal pilocarpine perfusion (12 mM, 40 min), and quantified. Result: All 3 compounds revealed anticonvulsant activity in PTZ- and pilocarpine-treated zebrafish larvae, with EEG recordings revealing reduction of epileptiform discharges. All 3 compounds showed anticonvulsant activity in the pilocarpine rat model for limbic seizures and the 6Hz psychomotor seizure mouse model for partial epilepsy. Antisense knockdown of the target kinase in zebrafish partially protected larvae from PTZ-induced seizures. Kinase overexpression experiments in zebrafish and mice are ongoing. Conclusion: These results suggest possible strategies for the discovery of new AEDs with novel mechanisms of action. seizures on BBB integrity in an experimental model of sepsis induced by cecal ligation and puncture (CLP) in rats. Method: Wistar rats were divided into control, CLP, PTZ and CLP plus PTZ groups. PTZ was administered to induce seizures and EEG was recorded. BBB permeability was assessed by measurement of Evans blue (EB) in the brain tissue. Immunohistochemistry was performed for occludin, p-glycoprotein (p-gp) and aquaporin (AQP)-4 proteins. Result: Arterial blood pressure decreased and rectal temperature increased in septic animals (P<0.05). The severity and duration of PTZinduced seizures were found to be increased in septic animals compared with intact animals. Immunoreactivity for p-gp increased in PTZ and CLP plus PTZ groups compared with CLP operated animals and controls (P<0.05). Immunostaining for AQP-4 was most intense in CLP operated rats compared with CLP plus PTZ and control groups (P<0.01). Conclusion: The results of this study show that sepsis enhances PTZinduced seizure severity and the degree of BBB disruption in rats. We suggest that alleviating the functioning mechanistic processes in sepsis may reduce the damage to barrier-type endothelial cells in seizures under septic conditions.
p606 ELECTROGRAPHIC BUT NOT BEHAVIOURAL MEASURES OF EPILEPTIC ACTIVITY ARE RELIABLE INDICATORS OF THE EFFICACY OF KETOGENIC DIET IN PENTYLENETETRAZOL ACUTE SEIZURE MODEL D. She, I. Kharatishvili, and D. Reutens Centre for Advanced Imaging, Brisbane, Qld, Australia
Purpose: Ketogenic diet (KD) is a high-fat low carbohydrate diet that exerts antiepileptic properties. Here, we performed electrographic quantification of the efficacy of KD on PTZ-induced seizures and compared it with commonly used observational outcome measures. Method: Epidural electrodes were implanted into 4 week-old male Sprague-Dawley rats bilaterally. Animals were then divided in 2 weightmatched groups and fed ad libitum either standard diet (STD, n=8) or KD (n=7), respectively (Specialty Feeds, WA, Australia), for 21 days. After that, acute seizures were induced under video-EEG control by continuous infusion of pentylenetetrazol (PTZ, 20 mg/ml, 0.1ml/min infusion rate) through the tail vein. Interictal and ictal behavioural and electrographic patterns were quantified and compared between the groups. Result: KD group had a lower number of interictal spikes (p=0.02), lower spike frequency (p=0.029) and spent less time in seizure (a percentage of time from beginning of infusion to tonic seizure, p=0.045, MannWhitney U). No significant difference in seizure duration was observed between the KD group and the STD group. The latency times and the threshold dose of PTZ to first overt myoclonic twitch, first spike, first clonic or first tonic seizure did not differ significantly between the groups. Conclusion: Our data suggest that quantification of electrographic ictal and interictal epileptiform activity can assess anticonvulsant properties of KD more reliably than commonly used outcome measures based on behavioral seizure characteristics.
p608 VARIOUS KINDS OF HYPERPOLARIZING AFTERPOTENTIALS IN NEOCORTICAL NEURONS DURING EPILEPTIC DISCHARGES V. Tsomaia, V. Okujava, T. Labakhua, S. Chipashvili, L. Mestvirishvili, and G. Kvernadze Iv. Beritashvili Centre Experimental Biomedicine, Tbilisi, Georgia
Purpose: The objective of presents investigation was the elucidation of intimate inhibitory mechanisms in cortical neurons leading to the arrest of epileptic ictal activity. Method: Experiments were performed on adult cats. Ictal activity was induced by repetitive electrical stimulation of the cerebral cortex. Intracellular microelectrodes were used for recording the neuronal electrical activity. The same electrodes were used for measuring the electrical parameters of the neuronal membrane (resistance) and for intracellular injection of specific compounds. Result: It has been established that prolonged hyperpolarization, which appears at the end of ictal discharges and which conditioned their arrest, should be induced by dual mechanism. On the one hand, it must be the result of the common mode of central inhibition produced by conductance inhibitory postsynaptic potentials (conductance IPSP) caused by an increased permeability of the membrane to chloride or potassium ions or to the both. On the other hand, the longer part of this hyperpolarization during which themembrane resistance is not charged, must be the result of the activation of the electrogenic pump, as revealed in experiments with intracellular injection of Vanadate which blocks the pump. Conclusion: In conclusoin one may suggest that during epileptiform discharges in neocortical neurons of the cat hyperpolarizing afterpotentials which follow PDS are of a composite nature and include three different components partially overlapping each other and forming one prolonged (sometimes undulating) deflection of membrane potential.
p607 BLOOD-BRAIN BARRIER INTEGRITY AND PENTYLENETETRAZOLE-INDUCED SEIZURE SEVERITY IN SEPTIC RATS M. B. Bahceci, N. Orhan, B. Ahishali, N. Arcan, C. Ugur, C. Gurses, and M. Kaya Istanbul University, Istanbul, Turkey
Purpose: The impact of seizures that emerge under a systemic inflammatory background in sepsis on the functional and morphological features of blood-brain barrier (BBB) is not fully understood. In the current study we investigated the effects of pentylenetetrazole (PTZ)-induced
p609 EFFECT OF MILD HYPOTHERMIA ON GLUTAMATE RECEPTOR EXPRESSION AFTER STATUS EPILEPTICUS L. Yu, and Y. Wang Children's Hospital of Fudan University, Shanghai, China
177 Abstracts
Purpose: Hypothermia has been shown to have neuroprotective effects in various models of neurological damage. However, its therapeutic effect on pediatric status epilepticus (SE) is still unknown. We conducted a study to investigate whether hypothermia can have an adjuvant effect on pilocarpine-induced status epilepticus in immature rats when combined with diazepam treatment. Method: SE were induced by pilocarpine on 21-day-old Wistar rats, which was followed by injection with diazepam and/or treatment with mild hypothermia. Rats were recorded with ECoG before and after SE. In addition, we analyze the necrosis and apoptosis of the neurons and detected the expression of GluR1, GluR2 and mGluR1 after SE through immunohistochemistry and Western blot in each group. We also calculated glutamate receptor mRNA in PCR. Result: We found that the spike-wave amplitude and frequency after SE during treatment with diazepam and hypothermia was significantly lower than treatment with diazepam alone. Mild hypothermia significantly reduced the number of cells undergoing necrosis and apoptosis. In addition, GluR1 was shown to be up-regulated by SE, while GluR2 was shown to be down-regulated. However, after combination therapy with diazepam and mild hypothermia for 8 hours, the expression of GluR1 was decreased and GluR2 was increased relative to the levels of diazepam alone treated juveniles. We also found that the expression of mGluR-1a was also decreased relative to diazepam alone. Conclusion: These findings suggest that mild hypothermia might further protect against pilocarpine-induced status epilepticus in immature rats by regulating glutamate receptor expression. positively related to epilepsy duration and suggest that targeting NMDA receptors may affect the course and severity of epilepsy.
p611 INACTIVATION OF THE CONSTITUTIVELY ACTIVE GHRELIN RECEPTOR ATTENUATES LIMBIC SEIZURE ACTIVITY IN RODENTS J. Portelli*, L. Thielemans, L. Ver Donck, E. Loyens*, J. Coppens*, N. Aourz*, J. Aerssens, K. Vermoesen*, R. Clinckers*, A. Schallier*, Y. Michotte*, D. Moechars, G. L. Collingridge, Z. A. Bortolotto, and I. Smolders* *Vrije Universiteit Brussel, Brussels, Belgium; Janssen Pharmaceutica, Beerse, Belgium; and University of Bristol, Bristol, UK
Purpose: Ghrelin is a pleiotropic neuropeptide that has recently been implicated in epilepsy, however its mechanism of anticonvulsant action is unknown. Method: In this study we used the in vivo rat model for pilocarpineinduced limbic seizures, the mouse pilocarpine tail infusion model, transgenic mice with a growth hormone secretagogue receptor (GHSR) deletion, electrophysiology in hippocampal slices, EEG recording in freely moving rats, and HEK293 cells expressing the human GHSR to determine inverse agonism, activation, desensitization, internalization and resensitization. Result: Ghrelin and the ghrelin-mimetic capromorelin attenuated pilocarpine-induced seizures in rats and mice. Experiments with transgenic mice ascertained that ghrelin requires the GHSR for its anticonvulsant effect. Unexpectedly we found that GHSR-/- mice had a higher seizure threshold than GHSR+/+ mice when treated with pilocarpine. This observation prompted us to look further into pharmacological modulation of the receptor. We discovered that abolishing the constitutive activity of GHSR by inverse agonism results in the attenuation of seizures and epileptiform activity. We confirmed that ghrelin's potential to rapidly desensitize the GHSR is followed by internalization of the receptor and a slow resensitization process. This, together with our present novel findings that different ghrelin fragments possess similar agonistic potencies but different desensitization characteristics on the GHSR, led us to elucidate that ghrelin probably attenuated limbic seizures in rodents and epileptiform activity in hippocampal slices due to its desensitizing effect on the GHSR. Conclusion: To the best of our knowledge, this constitutes a novel mechanism of anticonvulsant action whereby an endogenous agonist reduces the activity of a constitutively active receptor.
p610 EPILEPSY-DEPENDENT ARCHITECTURAL AND NMDA ABNORMALITIES IN MAM-PILOCARPINE RAT BRAIN F. Colciaghi*, A. Finardi*, P. Nobili*, G. Spigolon, A. Vezzani, and G. Battaglia* *IRCCS Neurological Institute Carlo Besta, Milano, Italy; University of Torino, Torino, Italy; and Mario Negri Institute for Pharmacological Research, Milano, Italy
Purpose: We have recently demonstrated that the occurrence of status epilepticus (SE) and subsequent seizures in malformed rat brain, i.e., the methylazoxymethanol-pilocarpine treated rat (MAM-PILO; Colciaghi F. Brain, 2011;134:282843) beget a pathologic process capable of modifying the morphology of pyramidal neurons and NMDA receptor expression/localization. Here we have verified whether the extent of the observed abnormalities might be related with epilepsy duration. Method: Epileptic MAM-PILO rats were analyzed respectively 35 days (early chronic stage -EC) and 36 months (chronic stage) after epilepsy onset. Spontaneous recurrent seizures were quantified with videoEEG-monitoring. MAM rats not experiencing SE were used as controls (MAM/noSE). In all rat groups we performed morphologic and molecular analysis. Result: Morphometric analysis of thionine-stained sections showed an epilepsy-dependent cortical thinning progression (20% and 35% after 3 and 6 months of epilepsy vs MAM/noSE rats) and decrease of hippocampal volume (45% and 60% after 3 and 6 months vs MAM/noSE). No differences were obtained between MAM-PILO EC and MAM/noSE rats. Further, we observed a time-dependent increase of dysmorphic neurons with neurofilament and NMDA over-expression (EC vs 3 months epilepsy, *p<0.05; EC vs 6 months epilepsy, ***p<0.001; 3 vs 6 months epilepsy, **p<0.01) and a significant hyperphosphorylation of NMDANR2B subunit associated with both malformed cortex and hippocampus of epileptic MAM compared to MAM/noSE brain. Conclusion: Our data indicate that in MAM-PILO rats the extent of structural and NMDA abnormalities of cortical pyramidal neurons are

p612 EFFECTS OF N-METHYL-D-ASPARTIC ACIDINDUCED SPASMS ON THE BRAIN: IN VIVO MAGNETIC RESONANCE SPECTROSCOPY M. Yum*, D. W. Kim, S. Kim*, L. Velisek, B. S. Lee*, and T. Ko* *Asan Medical Center, Seoul, Korea; Ilsan Paik Hospital, Inje University College of Medicine, Goyang; and New York Medical College, New York, NY, USA
Purpose: Infantile spasms are notorious for causing severe cognitive problems in children, even without detectable brain lesions. However,
178 Abstracts
the mechanisms of this catastrophic outcome are still unknown. We have developed animal models of infantile spasms and investigated the pathophysiology of infantile spasms. The aim of this study is to show the consequences of the NMDA-induced spasms in a rat model by in vivo analysis of magnetic resonance spectroscopy. Method: To compare the effects of multiple bouts of spasms on developing rat brains, prenatally betamethasone-exposed pups were subjected to 3 times of intraperitoneal NMDA-induced spasms (n=9) or saline injections (controls, n=9) on postnatal days 12, 13, and 15. 1H-magnetic resonance spectroscopy with ROI of cortex and basal ganglia (3x3x3mm3) and T2-weighted MRI, 24hr after the single and multiple spasms and at 7, 21, 35 days after last NMDA-induced spasms, were obtained. Linear mixed model was used for statistical analysis Result: There was no significant gross morphological difference on serial MRI between groups. Choline in basal ganglia and N-acetyl aspartate, choline, lipid-plus-lactate at 1.3 ppm in cortex showed significant changes by time (p<0.05). Only choline in basal ganglia showed significant decrease after spasms compared to controls (p=0.009). Conclusion: Despite the absence of structural abnormalities, NMDAinduced spasms result in a time and a region specific change of the metabolite pattern in the developing rat brain. Further histopathological and electrophysiological studies are needed to determine exact mechanisms of these changes.
p614 THE EFFICACY OF INTRAVENOUS VALPROATE COMPARED TO INTRAVENOUS PHENOBARBITAL IN CONTROLLING SEIZURES AMONG PEDIATRIC PATIENTS WITH BENZODIAZEPINE- REFRACTORY STATUS EPILEPTICUS: A RANDOMIZED CONTROLLED TRIAL L. K. F. Banta- Banzali, P. D. P. Obligar, J. R. Panlilio, and P. M. D. Pasco Philippine Children's Medical Center, Quezon City, Philippines
Purpose: To determine the efficacy and safety of intravenous valproate compared to intravenous Phenobarbital in controlling seizures among pediatric patients with benzodiazepine- refractory status epilepticus. Method: Status epilepticus patients two to 18 years of age were randomly divided into groups A and B and received 20 mg/kg loading dose of intravenous Phenobarbital and intravenous valproic acid, respectively. They were followed up for 24 hours for seizure outcome and adverse events. They were switched over to the other group if seizures were not controlled within one hour or there was seizure recurrence within 12 hours of treatment. Result: The duration of the status epilepticus at the time of presentation was <2 hours in all patients in Group A and in 82% of patients in Group B. All subjects in the two groups had good outcomes of treatment: seizure was controlled, no one left against medical advice and there was no mortality. Seizure recurrence was mainly seen during the first 12 hours in both study groups. There was no recurrence noted after 12 hours. Intravenous valproic acid and phenobarbital infusions were well tolerated. Elevation of SGPT was the most common adverse effect seen but the difference in proportion was not statistically significant between the two groups. Conclusion: Intravenous valproic acid is as effective and just as safe as intravenous phenobarbital as a second line non- sedative anticonvulsant for pediatric patients with status epilepticus who failed to respond to bolus doses of diazepam.
p613 SEIZURE ACTIVITY GENERATES CALCIUM-INDEPENDENT REACTIVE OXYGEN SPECIES VIA NADPH OXIDASE AND XANTHINE OXIDASE S. Kovac*, N. Hamil*, S. Williams*, A. Domijan, M. C. Walker*, and A. Y. Abramov *Department of Clinical and Experimental Epilepsy, London, UK; University of Zagreb, Zagreb, Croatia; and ION, London, UK
Purpose: Seizure activity has been proposed to result in the generation of reactive oxygen species (ROS), which then contribute to seizureinduced neuronal damage, cognitive dysfunction and further seizures. Seizure-induced production of ROS has been hypothesised to be due to calcium-dependent mitochondrial dysfunction. Method: We tested this hypothesis using fluorescence imaging techniques in rat glio-neuronal neocortical co-cultures using low magnesium to induce seizure-like activity and in ex vivo slices from chronically epileptic rats using confocal microscopy. Result: We found that prolonged seizure activity increases neuronal ROS production both in vitro and in vivo, and that ROS production in vivo is elevated during periods of spontaneous brief seizure-like activity. ROS production in vivo is brain-region specific with a higher rate of ROS production in CA1 compared to that in entorhinal cortex. The magnitude of ROS production in vivo is dependent on the duration of epilepsy. Increases in ROS in epileptic animals translated to a decrease in the major antioxidant glutathione measured in ex vivo slices. Seizure-induced ROS production was NMDA receptor-dependent and occurred alongside oscillatory calcium signals and a steady intracellular sodium increase in neuronal co-cultures. Unexpectedly, however, the production of seizureinduced ROS is not dependent upon mitochondrial dysfunction but is generated in a calcium-independent fashion initially through NADPH oxidase and later through xanthine oxidase activity. Consequently, inhibition of either of these enzymes reduced seizure-induced neuronal cell death. Conclusion: These findings demonstrate a critical role for calciumindependent ROS sources in seizure-induced neuronal death, and provide novel neuroprotective approaches.
p615 REFRACTORY STATUS EPILEPTICUS IN CHILDREN: LACOSAMIDE EFFICACY AND SAFETY S. Grosso*, N. Zamponi, E. Cesaroni, S. Cappanera, A. Verrotti, S. Nanni*, R. D. Bartolo*, and P. Balestri* *Policlinico S. Maria le Scotte, Siena, Italy; Ospedali RiunitiSalesi, Ancona, Italy; Ospedali Riuniti of Ancona, Ancona, Italy; and University of Chieti, Chieti, Italy
Purpose: Status epilepticus is a life-threatening neurologic emergency which needs a prompt therapeutic approach. When the first and secondline AEDs are ineffective to control SE, it is referred to as refractory SE (RSE). Lacosamide (LCM) was approved as an adjunct AED for partialonset seizures. It has unique mechanism of modulating voltage-gated sodium channels by enhancing their slow inactivation. To date, there are anecdotal reports of LCM use in RSE. To report on the experience with IV Lacosamide in children with RSE. Method: Pharmacy records were reviewed to identify patients with RSE who received IV LCM in our institutions. Data on demographics, response to therapy and adverse effects/outcomes were analyzed. All patients had continuous EEG monitoring. Result: 10 children (4 boys), age 316 years with RSE were given LCM. Four patients were in generalized non-convulsive RSE, 6 patients were in generalized convulsive RSE. The etiologies included idiopathic, cerebral palsy, neuronal migration disorders, and posterior reversible encephalopathy syndrome (PRES). IV LCM was added after traditional AEDs failed to
179 Abstracts
control the SE. RSE ceased in 6/10 patients whereas a partial response with cessation of NCSE but still frequent electrographic seizures were noted in another two. No effects were observed in the remaining two children. Conclusion: LCM is a useful adjunct in children with RSE. The IV formulation allows prompt administration in the intensive care unit setting. The drug demonstrated to be safe. Although larger controlled studies are needed, IV LCM seems to be a valid therapeutic option in children with RSE. Result: Five studies with 364 participants met the inclusion criteria. There was no statistically signiﬁ cance in SE controlled between Intravenous sodium valproate and Phenytoin (110/134 vs. 78/108 participants; RR 1.07 95% CI 0.91, 1.24). Compared with diazepam, sodium valproate had a statistically significant lower risk of time interval for control of RSE after giving drugs (8.8 7.4/20 vs. 26.6 26.7 participants; MD -17.80, 95% CI -29.94, -5.66), however, there was no statistically significant difference in SE controlled within30 minutes between the two groups (16/20 vs. 17/20 participants; OR 0.71, 95% CI 0.14, 3.66). There was no statistically significant difference in cessation from status between Intravenous sodium valproate and Levetiracetam (26/41 vs. 28/ 41 participants; OR 0.80, 95% CI 0.32, 2.01). Conclusions Intravenous sodium valprate was as effective as intravenous phenytoin for SE controlled and risk of seizure continuation. Conclusion: Intravenous sodium valproate was more effective or safer than other drugs in patients with status epilepticus.
p616 STIMULUS-INDUCED ICTAL EEG PATTERNS IN COMATOSE AND NON-COMATOSE ADULT PATIENTS WITH NONCONVULSIVE STATUS EPILEPTICUS S. Marca, G. Kuester, C. Lobos, C. Quiroz, R. Tapia, and M. Valencia Clinica Las Condes, Santiago, Chile
Purpose: To describe etiologies, morphology, localization, clinical findings, and correlation with spontaneous ictal patterns in comatose or non-comatose adults with nonconvulsive status epilepticus (NCSE) having ictal phenomena induced by alerting stimuli (SIRPIDs). Method: We retrospectively reviewed all consecutive prolonged/continuous EEG monitoring done between June 2009 and December 2011. We selected all comatose or non-comatose inpatients with electrographic or electroclinical findings consistent with NCSE having also ictal SIRPIDs during tactile, photic, auditory, or painful stimuli. We reviewed demographic and clinical features, etiology, morphology and localization of spontaneous and induced ictal patterns. Result: 26 patients were selected, 15 male; mean age: 55.3 yo (range: 1991). Most frequent etiologies were intracranial hemorrhage (six patients), previous or recent brain infarct (five patients), and severe head trauma (five patients). Most frequent induced ictal EEG pattern was focal rhythmic activity. Only three patients had clinical changes during ictal SIRPIDs. Location and morphology correlation with spontaneous ictal patterns was very high. Conclusion: Induced ictal EEG patterns in NCSE occur in different neurological conditions. More frequently they are focal and rhythmic, and very occasionally they are associated to clinical changes. They have very good correlation with spontaneous ictal patterns in terms of morphology and location. They are probably under-diagnosed if stimulus protocols are not consistently applied in comatose or non-comatose patients with NCSE. They should be identified and possibly require treatment, at least one preventive intervention.
p618 TREATMENT OF STATUS EPILEPTICUS IN THE ELDERLY WITH INTRAVENOUS LEVETIRACETAM S. Eue, M. Grumbt, A. Irimie, A. Latsch, M. Mueller, A. Schulze, and O. Sepsi Klinikum Bernburg GmbH, Bernburg, Germany
Purpose: We assessed the efficacy of LEV IV in the treatment of various types of status epilepticus (SE) in the elderly. Method: LEV IV was administered at dosages of 1000, 2000 or 3000 mg either as an infusion (1000 mg in 100 ml NaCl 0.9%, 15 minutes in nonconvulsive SE) or fractionated (500 mg in 20 ml NaCl 0.9%, 12 minutes in convulsive SE). Termination of SE was the effectiveness criterion (defined clinically in convulsive SE, electroencephalographically in nonconvulsive SE). Tolerability was assessed by evaluating treatmentrelated adverse events (AEs). Result: In the last five years we have treated 59 elderly patients (mean age 76.6 years, range from 65 to 95 years) with LEV IV with various types of SE. In general, LEV was administered as second-line therapy, after benzodiazepines. Overall, LEV terminated SE in 62.7% of the patients (37/59). LEV was most effective in terminating simple partial SE (12/15, 80%) but also effective in nonconvulsive SE (7/11, 63.3%) and complex partial SE (18/ 33, 54.5%). Almost of the patients had a symptomatic epilepsy (94.9%) and there was no case of a (secondary) generalized SE in this study. Serious AEs were not reported. Prolonged somnolence (especially in very old patients) was reported, but it was difficult to determine whether this was caused by LEV, benzodiazepines and/or post-seizure twilight state. Conclusion: LEV IV is an alternative in the treatment of partial convulsive (simple and complex partial) and nonconvulsive SE in the elderly.
p617 INTRAVENOUS SODIUM VALPROATE FOR STATUS EPILEPTICUS Y. Wu, X. Liu, Z. Chen, M. Ma, and S. Li The First Affiliated Hospital, Guangxi Medical University, Nanning, China
Purpose: To determine whether intravenous sodium valproate was more effective or safer than other drugs in patients with status epilepticus, we performed a meta-analysis. Method: A literature search was performed using Medline, Embase, the Cochrane Central Register of Controlled Trials CENTRAL. From 544 articles screened, 5 were identified as randomized controlled trials and were included for data extraction. Main outcomes were SE controlled, risk of seizure continuation. The meta-analysis was performed with the Random-effect model. The quality of the included studies was evaluated by Grade software.
Epilepsy Surgery 5 Wednesday, 03 October 2012

p619 MNESIC PERFORMANCE AFTER SELECTIVE TRANSCORTICAL AMYGDALOHIPPOCAMPECTOMY IN PATIENTS WITH TEMPORAL MESIAL SCLEROSIS R. L. Aguilar-Estrada, M. A. Alonso Vanegas, and A. R. Martinez Instituto Nacional de Neurologa y Neurociruga Manuel Velasco Suarez, Mexico City, Mexico
Purpose: Determine the effectiveness of selective transcortical amygdalohippocampectomy on seizure control and to assess the cognitive
180 Abstracts
performance, especially memory in patients with left mesial temporal sclerosis before and after surgery Method: We evaluated 28 patients with refractory epilepsy secondary to left mesial temporal sclerosis who underwent selective transcortical amygdalohippocampectomy by Inferior Temporal Gyrus (ITG) during the period between 2000 and 2010 at the National Institute of Neurology and Neurosurgery MVS. We performed preoperative study protocol, including neuropsychological tests to determine the preoperative condition. Patients were then retested to assess their postoperative condition. Result: They were followed an average of 56 months. The mean age was 35.14 years. 53.6% female, and 46.4% male. The 71.4% of patients had seizure control after surgery (Engel Ia and Ib), while 28.6% was in Ic and Id Engel. Before surgery 68% of patients had mild abnormalities in memory. As for the semantic fluency disorders 24% had mild, 47.5% with moderate and 28.5% with severe alterations. We found a positive relationship between age of disease onset and rate of improvement for the test of direct digits (R equal to 0.410, P = 0.37). There had not a more impaired mnesic performance postoperatively. Conclusion: Selective tanscortical amygdalohippocampectomy by ITG for patients with left mesial temporal sclerosis, while providing a comparable seizure control with international standards, was not related to a additional deficit verbal memory in patients. A good control of seizures in patients after surgery is associated with improved mnemonic performance in all categories, especially in verbal learning. The preoperative neuropsychological assessment showed Memory impairment in most of the patients, and worked as an important diagnosis and prognosis test.
p621 CLINICAL CHARACTERISTICS AND OUTCOME OF SURGERY FOR CHILDREN AND ADOLESCENTS S. J. Sattaluri, M. Panigrahi, and S. Madigubba Krishna Institute of Medical Sciences, Secunderabad, Andhra Pradesh, India
Purpose: To assess the clinical characteristics and postsurgical outcomes in children and adolescents with TLE. Method: Retrospective analysis of ictal VEEG, MRI, ictal SPECT, FDG PET, neuropsychology and pathology data was performed in 80 children and adolescents with refractory TLE who underwent surgery and had at least one year post-surgery follow-up. Presurgical evaluation was done with non-invasive protocol. Ictal SPECT & FDGPET was performed in all the patients with a discordance of ictal EEG & MRI data. Outcome was assessed according to Engel's outcome classification (Favourable: Engel's class I & IIA). Result: There were 24 children (212years) and 56 adolescents; The duration of follow up was 1278 (mean38.4) months and the age of onset of epilepsy ranged from 4m to 15 years. At the last follow up 18 (75%) children and 39 (69.6%) adolescents were seizure free. Auras were more common in adolescents, while developmental delay, below normal IQ and secondary generalized and multiple seizures were more frequent in children (p<0.05). Interictal-EEG showed multifocal and generalized discharges significantly more frequent in children than adolescents (p<0.001). Hippocampal sclerosis was the commonest pathology, noted in 76.8% of adolescents and 62.5% children. Isolated focal cortical dysplasia was more frequent in children (21%) than adolescents (12.5%). Dysplasia was more common in children <10 years (38.4%). After stepwise regression analysis, variables found to be significant (p=<0.05) and predicting an unfavourable outcome were acute post operative seizures and non-lateralizing ictal-EEG findings. Conclusion: Children with TLE have distinct clinica, EEG and pathology features when compared to adults. Favourable outcome can be obtained in children and adolescents after surgery for TLE.
p620 EPILEPSY SURGERY: LEAVING THE LESION BEHIND? S. Chinnasami, A. W. Mcevoy, C. Scott, T. Wehner, J. Duncan, and B. Diehl The National Hospital for Neurology and Neurosurgery, London, UK
Purpose: To describe two patients with epileptogenic zones distant from MRI lesions. Method: We reviewed 246 patients who underwent resections for focal epilepsy over the last 5 years to identify patients with epileptogenic zones and resections distant from MRI lesions, in non-lesional brain regions. Result: Two of 246 patients were identified. Patient 1: 36 year old man with daily seizures (asymmetric tonic arm posturing with falls) since childhood. Scalp EEG showed bilateral slowing and midline ictal patterns. MRI revealed left hippocampal sclerosis, FDG-PET showed right fronto-parietal hypometabolism. Intracranial EEG study designed on careful analysis of semiology and neurophysiological findings showed seizures from the right supplementary motor area. Resection of ictal onset zone led to seizure freedom, with 9 months to date (Histopathology: non-specific). Patient 2: 30 year old man with daily automotor seizures and remote history of visual auras. Scalp EEG showed rare sharp waves in the left temporal region; ictal EEG lateralized to left hemisphere. MRI revealed cortical dysplasia or low grade glioma in the upper bank of the left calcarine fissure with normal temporal lobes. Intracranial EEG evaluation covering lesion and left temporal lobe confirmed left hippocampal seizure onset. Following left anterior temporal lobe resection, he has been seizure free for 2 months (Histopathology: hippocampal gliosis) Conclusion: The epileptogenic zone may be distant from MRI lesions. Careful analysis of clinical, neuroimaging, and electrophysiological data is crucial, even in the presence of a structural lesion. Longer follow up is needed to assess ultimate outcome.
p622 EPILEPSY SURGERY IN CHILDREN WITH DIFFICULT-TO-TREAT EPILEPSY IN THE SOUTH REGION OF SWEDEN LONG-TERM FOLLOW-UP T. C. Hallbk*, E. Tideman, J. Lundgren, and I. Rosn *Paediatric Neurology, Sahlgrenska Academy, Gothenburg, Sweden; and Lund, Sweden
Purpose: Resective epilepsy surgery in early childhood has become an important treatment option for selected infants and children with epilepsy. We describe experience and clinical outcomes in all children who underwent resective surgery for epilepsy in the south region of Sweden. The study is a long-term follow-up of all children who underwent epilepsy surgery, at the University Hospital in Lund from the beginning in 1991b until 2007. Method: All children under 18 years of age who had resective surgery for the purpose of treating epilepsy within the south region of Sweden at the Lund University Hospital epilepsy surgery program between the start in 1991 and 2007 were assessed for cognitive functioning, mental health, present psychological, occupational and social functioning, QOL and expectations. Followup was between 5 and 21 years. Review of medical documents for demographic data and seizure-related characteristics such as etiology, post-operative seizure frequency, pre and post-operative cognitive function, long-term complications and re-operation rates were analyzed by retrospective examination of the clinical records. Result: Forty-seven children were included in our cohort with a median age at surgery of 8 years (range 0.518.16 years). Surgical procedures
181 Abstracts
comprised 15 lesionectomies, 16 lobar resections, six multilobar resections, six functional hemispherectomies, two callosotomies, one disconnection, and one subpial transection. 19/47 (40%) children underwent reoperation. Three of these were disconnections of hypothalamus hamartomas. 23/47 (50%) children achieved seizure freedom. 6/47 (13%) demonstrated more than 75% improvement in seizure frequency, 7/47 (15%) 50 - 75% improvement in seizure frequency and no children had an increase in seizure frequency. Postoperative complications included subsequent shunt procedure in 1/7 (14%) children undergoing hemispherectomy, one child had a peroperative hemorrhage without any sequel and one an infraction with a subsequent light paresis. Two children were dead at follow-up. One died from SUDEP and one while having an epileptic seizure. Conclusion: Epilepsy surgery in children offers suitable candidates a good chance of significantly improved seizure outcome even after longterm follow-up. Purpose: Epilepsy is a common and disabling condition. Medical treatment fails to control seizure in about 2030% of patients. The burden is higher in developing countries because of the number of patients, insufficient infrastructure and problem of access to drugs and explorations. Epilepsy surgery was suggested to offer an extremely powerful treatment option. Method: Fifty one patients with intractable complex partial seizure were treated with temporal lobectomy. We use non-invasive methods, i.e. the clinical seizure pattern; interictal and ictal scalp EEG; magnetic resonance imaging (MRI); neuropsychological testing and all converged to indicate a localized abnormality. Result: Thirty one of 51 (60%) are seizure and aura-free (Engel's class IA) with a mean follow-up time of 4 years (17 years), and twelve (23, 5%) no longer take antiepileptic drugs. Our series includes twenty nine cases (57%) of hippocampal sclerosis and twenty two cases (43%) of mass lesions mostly represented by DNET and cortical dysplasia. Our study takes into account outcome predictive factors especially age of onset, febrile convulsion history, duration of epilepsy, preoperative secondarily generalized tonic-clonic seizure, age at surgery and preoperative seizure frequency. Conclusion: The results of our series are comparable of results obtained in developed countries, which is encouraging to develop this discipline despite the material constraints.
p623 RESECTIVE SURGERY BY INTRACRANIAL MONITORING IMMEDIATELY AFTER CORPUS CALLOSOTOMY IN ADULT NON-LESIONAL FRONTAL LOBE EPILEPSIES Y. Cho, B. I. Lee, K. Heo, M. K. Lee, D. Kim, and J. W. Chang Severance Hospital, Yonsei Univ. College of Medicine, Seoul, Korea
Purpose: Non-lesional frontal lobe epilepsy (FLE) often fails to localize ictal onset because of its rapid propagation through corpus callosum. Successful identification of focal onset and resective surgery long after corpus callosotomy (CC) has been reported in childhood epileptics, especially Lennox-Gastaut syndrome. We performed immediate intracranial monitoring after partial CC and resective surgery in adult non-lesional FLE patients. Method: Three adult FLE without lateralizing features received resective surgery between 2008 and 2011. Subdural electrodes were placed immediately after CC and extra-operative intracranial monitoring was done from the next day of CC. Result: All had frequent seizures (one, 8 per month; two, daily attacks) before surgery. Scalp video-EEG monitoring confirmed frontal lobe-origin, but failed to lateralize seizure onset. Semiologic features were not informative (one had predominantly tonic posturing; two had hypermotor seizures) for lateralization. Neuroimaging findings were not helpful. Intra-operative electrocorticography after partial anterior CC failed to lateralize onset, and bilateral symmetric subdural electrodes were placed over frontal lobes. Extra-operative monitoring showed lateralized interictal discharges in all, and two of them also showed localized ictal onset. One patient didn't experienced seizure. Two patients had clearly lateralizing semiologic features which were never found on scalp monitoring. Seizure outcome was successful: two had Engel 1B (rare simple partial seizures only) and one, who hadn't have seizure, had 2A outcome. None had significant post-operative neurological deficit. Conclusion: Simultaneous intracranial monitoring following partial CC may be considered an alternative option that enables resective surgery in patients with non-lateralized FLE.
p625 COMPLICATIONS OF EPILEPSY SURGERY IN SWEDEN 19962010: RESULTS FROM THE SWEDISH NATIONAL EPILEPSY SURGERY REGISTER J. Bjellvi*, A. Edelvik*, G. Ekstedt*, R. Flink, B. Rydenhag*, and K. Malmgren* *Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; and Uppsala Akademiska Hospital, Uppsala, Sweden
Purpose: Patients need detailed risk information as part of pre-surgical counseling when considering epilepsy surgery. In this study we have investigated major and minor complications related to epilepsy surgery in Sweden 19962010. Method: The Swedish National Epilepsy Surgery Register provides population-based data on all patients (adults and children) operated in Sweden since 1990 (completely prospective from 1995), including extensive pre-operative data, surgical data including complications, and postoperative follow-up. We have analysed complications in relation to type of surgery for the period 19962010. Complications are classified as major (affecting daily life and lasting >3 months) or minor (resolving within 3 months). Result: 858 therapeutic epilepsy surgery procedures were performed 19962010, of which 153 were reoperations. There were no postoperative deaths. Major complications occurred in 23 procedures (2.7%), minor complications in 66 (7.7%). In temporal lobe resections (N=518), there were 13 major (2.5%) and 39 minor complications (7.5%), in extratemporal resections (N=272) 9 major (3.3%) and 23 minor complications (8.5%), and in nonresective procedures (N=61) 1 major (1.6%) and 4 minor complications (6.6%). Conclusion: This is the largest reported prospective series of complication data in epilepsy surgery. The complication rates comply well with published results from single centers, confirming that epilepsy surgery performed in the six Swedish centers is safe. Compared to previously published results from the same register [Rydenhag et al, Neurosurgery, 49:5157, 2001], the complication rates are lower for any surgical procedure as well as for temporal resections, extratemporal resections, and nonresective procedures.
p624 RESULTS OF EPILEPSY SURGERY WITH NON INVASIVE METHODS MOROCCAN EXPERIENCE ABOUT 51 CASES A. Mrani, A. Khamlichi, H. Belaidi, F. Lahjouji, and R. Ouazzani Hospital of Specialities, Rabat, Morocco
182 Abstracts
p626 SURGICAL EXCISION OF TEMPORAL GLIONEURONAL TUMOURS RISK FACTORS FOR PSYCHIATRIC SEQUELAE? O. Solanke*, R. Chelvarajah, J. Moriarty, C. E. Polkey, and R. Selway *Guy's, King's and St. Thomas Hospitals Medical School, London, UK; Queen Elizabeth Hospital Birmingham, Birmingham, UK; and King's College London, London, UK
Purpose: We present data from our surgical series to investigate the association of anxiety and depression with surgical excision of temporal glioneuronal tumours. We suggest risk factors for development of these psychiatric symptoms. Method: We reviewed the case-notes of each patient. Telephone interviews were carried out with patients/carers to complete the Hamilton Anxiety Rating Scale (HARS) and the Becks Depression Inventory (BDI). Result: Thirteen patients underwent surgery for resection of temporal glioneuronal tumours. Ages at surgery ranged from 11 to 54. Six patients had no anxiety (HARS score <17) or depression (BDI score 110) after surgery. Five achieved seizure freedom from the time of surgery. One seizure-free patient who suffered mental health problems prior to surgery encouragingly saw resolution of these symptoms post-operatively. Four of the five seizure-free patients had non-dominant side surgery. Seven patients experienced psychiatric difficulties post-operatively, one of which was diagnosed with psychiatric disturbance pre-operatively. All continued to have seizures post-operatively. Four had moderate and severe anxiety (HARS score above 25) of which two had moderate depression (BDI score 2130) and one patient had borderline clinical depression (BDI score 1720). These latter five patients had dominant side surgery. Conclusion: While psychiatric disability is relatively common with surgical excision of temporal glioneuronal tumours, achieving seizure freedom following surgery can be associated with the absence of psychiatric sequelae and in one of our cases resolved pre-existing psychiatric disturbance. Non-dominant side surgery may be associated with achieving seizure freedom. We postulate that this perceived association may be due to the degree of surgical resection. Result: In 4 of 19 cases MSI determined localization regionally correlated to video-EEG data (that is, showed the same lobe). In thirteen cases MSI showed additional epileptogenic foci that ictal video-EEG was unable to identified. In six cases, MSI was used to guide invasive electrodes to locations that otherwise would not have been targeted and provided unique localization data, not evident from other imaging modalities, that strongly influenced the surgical management of the patient. In seven patients, for whom data from invasive electrocorticography were available, the MSI was highly correlated with the zone of seizure origin identified by electrocorticography. Conclusion: Magnetic source imaging can provide critical localization information that is not available when other noninvasive methods, such as video-EEG and MRI, are used.
p628 EPILEPSY SURGERY FOR REFRACTORY EXTRATEMPORAL EPILEPSIES. UP TO TEN YERS FOLLOW UP A. Siatouni*, S. Gatzonis*, N. Georgakoulias, S. Korfias*, C. Tsekou*, T. Bouras*, T. Papasilekas*, E. Aggelopoulos*, M. Papathanassiou*, P. Patrikelis*, I. Kaskarellis*, E. Patsouris*, and D. Sakas* *Athens Medical School, Athens, Greece; and Athens General Hospital G. Genimatas, Athens, Greece
Purpose: The surgical approach is an established method for treatment of refractory partial epilepsy. The presurgical evaluation in patients with extratemporal epilepsies is aiming to define the boundaries of epileptogenic zone and the function of possibly removable cortical area in order to plan the operative procedure, and to estimate the post surgical prognosis. We present the results of the surgical treatment of 31 patients suffered from extratemporal refractory focal epilepsy who continue to be monitored regularly in our department. Method: 31 patients, aged 1143, 25 men and 6 women, who were treated surgically for drug-resisting epilepsy of extratemporal origin. 9 patients suffered from non-lesional epilepsies. 22 patients suffered from lesional epilepsies which resulted from malformations of cortical development, vascular malformations, tumors and gliosis from old injuries or surgery. The presurgical protocol includes history, EEG, long term Video-EEG, high resolution structural and functional imaging techniques and neuropsychologic studies in order to compose a clinical scenario for the topography of epileptogenic zone. All of them underwent invasive long term-EEG monitoring as a standard procedure for the precise localization of the pacemaker zone and cortical stimulation in the definition of eloquent cortical areas Result: 58% (18/31) of the patients are classified as Engel I after the surgical procedure (follow-up 110 years). 8 (25, 8%) patients show worthwhile seizures reduction (Engel II, III) and 5 patients do not show any appreciable improvement (Engel IV) Conclusion: Surgical treatment of extratemporal epilepsies is a favorable therapeutic procedure which offers more than 50% seizure free rates and low incidence of serious complications.
p627 MEG VERSUS EEG LOCALIZATION FOR PRESURGICAL EVALUATION OF THE INTRACTABLE EPILEPSY A. Koptelova*, A. Melikian, N. Arkhipova, A. Stepanenko, A. Golovteev, A. Kozlova, O. Grinenko, and T. Stroganova* *Moscow State University of Psychology & Education, Moscow, Russian Federation; Burdenko Neurosurgical Institute, Moscow, Russian Federation; and Moscow City Hospital No 12, Moscow, Russian Federation
Purpose: Magnetoencephalography (MEG) and magnetic source imaging (MSI) are techniques that have been increasingly used for preoperative localization of epileptic foci. To help elucidate the value of MEG, we assessed the results of whole-head MEG versus video-EEG in the case management of patients undergoing epilepsy surgery. Method: We studied 19 patients with suspected focal epilepsy who underwent interictal and ictal video-EEG and, subsequently, interictal and ictal MEG. Nine patients underwent surgical resection of suspected epileptogenic zone and seven of them invasive electrocorticography. The results of MSI were classified to define epileptogenic foci according to the clastering of interictal and ictal spikes recorded during a 4-hour recording session. The data were analyzed to determine to what extent the results of MSI correlated with video-EEG determined irritative zones.
Epilepsy Surgery 6 Wednesday, 03 October 2012

p629 BASAL TEMPORAL LANGUAGE TESTING IN PATIENTS UNDERGOING INVASIVE EEG STUDIES C. Scott*, S. Kovac, T. Wehner, R. Rodionov, A. W. Mcevoy, and B. Diehl
183 Abstracts
*Telemetry Unit, London, UK; Department of Clinical and Experimental Epilepsy, London, UK; UCL Institute of Neurology, London, UK; and National Hospital for Neurology & Neurosurgery, London, UK
Purpose: The involvement of basal temporal lobe in language and pure alexia has been previously described but not widely investigated. We reviewed electrical cortical stimulation (ECS) in all patients with basal occipito-temporal intracranial electrode coverage for localisation of the ictal onset zone performed over the past 3 years, in whom mapping of that area was performed (n=7). Method: ECS of basal occipito-temporal areas and testing of reading, naming, writing and comprehension was performed using 50Hz stimulation, 35s duration, mean 4mA. 5/7 patients were left language dominant and 2/7 had bilateral speech representation. 2/7 had lesions (1 mesial temporal, 1 basal temporal). Language mapping was scored by two independent reviewers and errors influenced by after discharges were excluded. Result: ECS was performed successfully in 6, in one patient extensive mapping was impossible due to after discharges. Basal language areas were identified in 3 patients. The number of contacts showing some language deficit was 23 per patient (total 8 contacts), all overlying the fusiform gyrus (5.88cm from the tip of temporal pole). Object naming, auditory comprehension, reading and reading comprehension were most commonly disrupted by ECS. Conclusion: That we found basal temporal language area in only 3 of 6 patients may reflect sampling error; comprehensive coverage of this area is technically difficult, the eloquent area may be small and dispersed, and in some patients lesions may displace function. When identified, it can provide useful information to aid counselling regarding postoperative naming difficulties if resection of this area is required. in an extratemporal location, however reoperation failed to improve the outcome in the majority.
p631 LONG-TERM OUTCOME OF SURGERY IN PATIENTS WITH EXTRATEMPORAL EPILEPSY P. Hanakova*, R. Kuba, M. Brazdil, J. Hemza, Z. Novak, J. Chrastina, M. Hermanova, H. Oslejskova*, and I. Rektor *Epilepsy Center Brno, Brno University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic; Central European Institute of Technology (CEITEC), Masaryk University, Brno, Czech Republic; Epilepsy Center Brno; St. Anne's University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic; and St. Anne's University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic
Purpose: To evaluate long-term efficacy of surgery in patients with refractory lesional and non-lesional extratemporal epilepsy. Method: We retrospectively analysed 73 patients (46 men and 27 women) with extratemporal epilepsy, who underwent resective surgery in St. Anne's University Hospital in Brno, the Czech Republic, between August 1995 and January 2010. The average age at surgery was 28.311.4 years (range 1- 51 years). Magnetic resonance imaging did not demonstrate a lesion in 32.9% of patients. Surgical outcome was annually assessed by using Engel's modified classification one until five years after surgery and at the latest follow-up visit. Result: Following the surgery, Engel Class I outcome was found in 52.1% after 1 year, in 55.0% after 5 years and in 50.7% of patients at the last follow-up (the average 6.153.84 years) in the whole group. A statistically significant association was found between tumour etiology and good outcome (v 2(2) = 6.67; p=0.035). There was confirmed a statistically significant association between a lesion on the preoperative magnetic resonance imaging and the reduction in seizure frequency (v2 (1) =6.62; p=0.01). No statistically significant difference between duration of epilepsy and surgical efficacy was found. Conclusion: Our results are comparable to recent publications. 5055% of patients with extratemporal epilepsy are seizure-free after surgery.
p630 SURGERY FOR TEMPORAL LOBE EPILEPSY WITH NORMAL MR IMAGING: SEIZURE OUTCOME, YIELD OF RE-EVALUATION AND OUTCOME FOLLOWING REOPERATION M. M. Ali, W. J. Hader, N. Pillay, S. Wiebe, P. Federico, L. B. Espinosa, and M. Opoko-Darko Calgary University, AB T2N2T9, Canada
Purpose: To review the seizure outcome, location of seizure recurrence, and outcome of reoperation for temporal lobe epilepsy with normal MR Imaging. Method: We retrospectively reviewed the records of all patients who underwent temporal lobe surgery with nMRI between 2000 and 2010 at Calgary Epilepsy Program. We reviewed the location of seizure recurrence and seizure outcome following reoperation. Result: We identified 47 patients who underwent TLE surgery with nMRI.32 patients underwent anteromesial temporal lobe resection, 11 trans cortical selective amygdalo-hippocampectomy, and 4 neocorticectomy. Seventeen patients underwent intracranial electrodes implantation prior to the resection. On average follow-up of 51 months, 29 patients (61%) had either Engel class I or II outcome. Fourteen out of the 18 remaining patients (78%) patients had re-evaluation including repeat video-EEG monitoring and high resolution MRI and intracranial monitoring (n=5). The focus of recurrence was: contralateral temporal 4 (28%), ipsilateral posterior neocortical 7 (35%), Insular 1 (7%), Frontal 1 (7%), and residual hippocampus in 1 (7%). Out of the 7 patients who had re-operation, only 1 patient (14%) was seizure free on last follow-up. Conclusion: Temporal lobe resection in well-selected patients with nMRI can provide favorable rates of seizure freedom. The location of recurrence in patients re-evaluated after failure was felt to be in the contralateral temporal lobe or ipsilateral posterior temporal lobe rather than
p632 PRACTICAL VALUE OF INTRAOPERATIVE ELECTROCORTICOGRAPHY IN CHILDREN P. Krsek, R. Lesko, A. Jahodova, M. Kudr, J. Zamecnik, V. Komarek, and M. Tichy Motol University Hospital, Prague, Czech Republic
Purpose: To study a practical value of intraoperative electrocorticography (ECoG) in pediatric excisional epilepsy surgery. Method: ECoG recordings performed in 90 children operated on because of intractable focal epilepsy in Motol Epilepsy Centre between 2002 and 2011 were retrospectively analyzed. Completeness of resection of cortical regions exhibiting significant ECoG abnormities was assessed. Findings were related to surgical, histological and seizure outcome data of patients. Result: 37 patients had ECoG only before the resection, 34 subjects underwent ECoG both before and after resections, 19 patients had ECoG after a long-term invasive monitoring. Based on ECoG findings, surgical plans were modified in 27 subjects (Group 1); in 54 patients were not changed (Group 2). In nine patients, there was a reason for a modification that was not done because of surgical causes (Group 3). All the groups
184 Abstracts
were etiologically diverse. In Group 1, modifications of surgical plans were equally based on ECoG findings before and after resections. Histology of the brain tissue in extended resections was always abnormal. There were no significant differences in proportion of resections assessed as complete as well as seizure outcomes between Groups 1 and 2. No subjects in Group 3 were rendered seizure-free. Conclusion: ECoG findings modified surgical plans in a significant subgroup of pediatric epilepsy surgery patients, regardless the etiology. Both pre-resective and post-resective ECoG was useful in our series. Longterm seizure outcomes in patients undergoing extended resections according to ECoG were comparable to subjects with no need of surgical plan modifications. Supported by grants CZ.2.16/3.1.00/24022 and IGA NT/11460-4. technologies to study chronotopology of epileptogenesis has been elaborated. Electroclinical diagnostic examination and surgical treatment results in over 200 drug-resistant temporal epilepsy patients aged 1950 were analyzed. Result: Based on critical chronotopology of electrographic trait-markers particularities of preclinical, early (temporal) and late (extratemporal) epileptogenesis were depicted reflecting clinical-neurophysiologic forms of focal and multifocal temporal epilepsy. Monotemporal epileptogenesis is characterized by peculiar localization of the epileptic focus: in our series ECoG-SEEG studies revealed a combined neocortical and limbic (hyppocampus, amygdala) damage in 79% of patients. This optimizes technology of open surgical treatment (anterior temporal lobectomy) with additional use of multiple subpial transection in eloquent cortex. Morphofunctional basis of extratemporal links of epileptogenesis is amounted by integral brain systems ensuring cerebral homeostasis: according to EEG-SEEG data limbical-brainstem pathways of epileptizaton were followed-up hippocampus and amygdala via thalamic anterior nuclei are involved in cyclic Papez and Livingston-EscobarYakovlev systems, forming multifocal forms (bitemporal, fronto-temporal epilepsy etc.), which is of importance in neuromodulating interventions. Conclusion: The presented date demonstrated that neurophysiologic markers appear a reliable method to evaluate regularities of epileptogenesis at the cortical, limbic and brainstem structure levels. The dynamics of epileptogenesis optimizes strategy of differentiated surgical treatment of drug-resistant temporal lobe epilepsy.
p633 MULTIMODAL 3D VISUALISATION FOR PLACEMENT OF INTRACRANIAL EEG ELECTRODES R. Rodionov*, C. Vollmar, A. Miserocchi, C. Micallef, B. Diehl, A. W. Mcevoy, and J. Duncan* *UCL Institute of Neurology, London, UK; University of Munich, Munich, Germany; and National Hospital for Neurology and Neurosurgery, London, UK
Purpose: Accurate placement of intracranial EEG electrodes is crucial for optimal results and to mimimize risk. Multimodal neuroimaging provides very useful data for ensuring more accurate and safer placement of electrodes. We developed and implemented a multimodal, interactive 3D visualisation pipeline for presurgical planning and import of this information into the neuronavigation system for use at the time of surgery. Method: Images of different modalities (MRI, SPECT, PET, fMRI, DTI, EEG-fMRI, MEG) are coregistered into the base T1-weighted MR image and converted into colour-coded volume- or surface-rendered 3D models. A 3D model of surface veins serves as a landmark for navigation and indicates areas requiring special care during surgery. The composite dataset is used to plan electrode placement. All images are coregistered to the navigational T1 image acquired shortly prior to the surgery and converted into binary labels and fused onto the navigational image. The resulting image is used to create 3D models which is uploaded on the neuronavigation system. Result: The method was applied in 20 patients with refractory focal epilepsy. The multimodal display helped electrode placement and accuracy of placement of 3D models was confirmed intraoperatively. Conclusion: 3D models of multimodality neuroimaging data aid accurate and safe placement of intracranial electrodes.
p635 CURRENT STATUS AND PHARMACOECONOMICS OF EPILEPSY SURGERY IN DEVELOPING COUNTRIES LIKE INDIA M. M. Mehndiratta G.B.Pant Hospital, New Delhi, India
Purpose: To describe the Current Status and Pharmacoeconomics of epilepsy surgery in developing countries like India. Method: A survey was conducted through email to different institutes engaged in epilepsy surgery to calculate the Cost of investigations, medical and surgical treatment for epilepsy. Result: As per the recent census of Government of India, the population of India is more than one billion. There are only 1000 neurologists to serve this population. At any given time there are around 10 million epileptics in India. Approximately two million epileptics require surgery for their uncontrolled epilepsy. If a person with epilepsy undergoes for workup for epilepsy surgery, the expenses involved on investigations like reassessment by conventional EEG, epilepsy protocol MRI brain, SPECT, Video-EEG, Neuro-psychological analysis etc will be approximately US$ 1000. The cost of epilepsy surgery or implantation of Vagus Nerve stimulator is likely to be around US$ 6000. If we sum up expenses in all categories at a minimum cost level, it is likely to be 7800 USD. India is classified in the category of Low income group by WHO ranked 160th in the world and per capita income by the Atlas method for India is USD 530. Conclusion: In the absence of comprehensive medical insurance scheme and because of low PCI, to afford epilepsy surgery by an average Indian is literally is out of reach for a common man.
p634 CHRONOTOPOLOGY OF NEUROPHYSIOLOGIC MARKERS FOR EARLY AND LATE EPILEPTOGENESIS AND SURGERY OF DRUG-RESISTANT TEMPORAL LOBE EPILEPSY S. Kravtsova, T. Stepanova, V. Kasumov, V. Bersnev, R. Kasumov, and K. Sebelev Russian A.L. Polenov Neurosurgical Institute, St. Petersburg, Russian Federation
Purpose: Over 30% of epileptic patients suffer uncontrolled by medication seizures. This study aimed to examine neurophysiologic mechanisms of epileptogenesis and to optimize surgical treatment of drug-resistant temporal lobe epilepsy. Method: A program including neurophysiologic (EEG, ECoG, SEEG via subdural and deep electrodes) and visualizing (functional MRI)
p636 MITOCHONDRIAL DISORDERS IN THE NEOCORTEX OF PATIENTS WITH REFRACTORY EPILEPSY M. A. Alonso Vanegas*, V. Campos*, J. Villeda*, F. Fernandez*, and K. Carvajal
185 Abstracts
*Instituto Nacional de Neurologa y Neurociruga, Distrito Federal, Mexico; and Instituto nacional de pediatria, Distrito Federal, Mexico
Purpose: In this study we evaluated activity of NADPH-d, CKmit, VDAC, NOS and NeuN in neocortical tissue of patients with refractory temporal epilepsy Method: We studied 10 cases with temporal epilepsy (8 males and 2 females). 4 with epilepsy secondary to tumors and 6 cases with mesial temporal lobe epilepsy. All patients were studied according to standardized presurgical protocol and submitted to temporal lobectomy and amigalohippocampectomy. We studied activity and distribution of NADPH-d, CKmit, VDAC, NOS and NeuN, in biopsies of the temporal cortex. The samples were studied by the NADPH-d- technique and immunohistochemistry. Result: NADPH reactive neurons were localized preferentially in layers III and VI and in the subjacent white matter of the temporal cortex, the neurons in layer VI were larger and significantly reactive to NADH-d. VDAC and NeuN expression was enhanced in layer VI, whereas CKmit and NOS showed a decrease in all cases, Epileptic neurons also showed hypertrophy, cytomegaly, dysmorphic and hyperchomatic, morphology. Ballon cells were observed in 3 patients. We also observed expression of NADPH subunits in reactive astrocytes and all components of the neurophil. Conclusion: These results suggest a causal relationship between the activities of respiratory enzymes and metabolic processes that contribute to damage, oxidative and /or mitochondrial dysfunction that can be both an important cause and/or a consequence of prolonged seizures and could represent changes in brain plasticity in these patients. This study was supported by the CONACYT of Mexico (grants J010.0170/2010) and the Academy of Sciences of Hungary (grantsETT577/2006, RET67/2005). of these had sustained seizure freedom since surgery (ILAE class 1 and 2). There is a strong correlation between aetiology and seizure outcome in this prospective, population based series.
p638 FUNCTIONAL HEMISPHERECTOMY FOR CONTINUOUS SPIKE WAVE IN SLOW WAVE SLEEP (CSWS) IN PATIENTS WITH EARLY VASCULAR INSULT: FURTHER EVIDENCE OF THE ROLE OF THE THALAMUS IN PATHOGENESIS H. Cross*, A. Mctague*, A. Mclellan, V. Ramesh, and W. F. Harkness *UCL-Institute of Child Health, London, UK; Royal Hospital for Sick Children, Edinburgh, UK; Department of Paediatric Neurology, Newcastle, UK; and Great Ormond Street Hospital for Children, London, UK
Purpose: Continuous spike wave in slow wave sleep (CSWS) is an epileptic encephalopathy commonly associated with structural brain lesions. We present two cases where a dramatic developmental response was seen with the abolition of CSWS following hemispherectomy. Method: Review of clinical, MRI and EEG data. Result: Case 1 presented age 7 with multiple seizure types in association with a congenital left hemiplegia secondary to a right MCA infarct. Her epilepsy rapidly escalated to 200300 seizures per day, with obtundation and developmental stagnation associated with CSWS resistant to multiple treatments including corticosteroids and benzodiazepines. Right functional hemispherectomy at age 10 resulted in a dramatic return of abilities, particularly speech. At 15 she is now seizure free, attends school and continues to make developmental gains. Case 2 presented with seizures and a right hemiplegia in the first year of life due to a perinatal left MCA infarct. Initial right focal motor seizures gave way to periods of behavioural change and developmental regression associated with CSWS. Overt seizures resolved, but the CSWS remained resistant to medical treatment. A left functional hemispherectomy performed at 11 years of age, led to resolution of behavioural problems and marked improvement in learning abilities. Conclusion: Hemispherectomy is an effective treatment for CSWS in the context of hemi-pathology. These two cases add to the literature and we suggest that earlier consideration be given to functional hemispherotomy, even in the absence of overt seizures.
p637 SEIZURE OUTCOME AND ETIOLOGIES IN FRONTAL LOBE EPILEPSY SURGERY IN SWEDEN 19902009 B. Rydenhag*, R. Flink, and K. Malmgren *Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Uppsala Akademiska Hospital, Uppsala, Sweden; and Sahlgrenska Academy at Gothenburg University, Gteborg, Sweden
Purpose: To present two-year outcome data from a Swedish national prospective population based series of adults and children operated for frontal lobe epilepsy 19902009. Method: Data from the Swedish National Epilepsy Surgery register were analysed for 19902009. The register includes data from all surgical procedures in Sweden. All patients who had frontal lobe procedures, except reoperations, and who had a two-year follow up were included. The aetiology was also analysed in relation to outcome. Result: Demographic data for the 128 identified patients are: seizure onset at 8.0 years (3.014.0) (median age (interquartile range (Q25;Q75)); surgery at 22.0 years (13.035.0); duration of epilepsy: 9.0 years (3.919.5). 57/128 patients (45%) were seizure free, of these 48 (38%) had sustained seizure freedom (ILAE class 1 and 2) at the two-year follow up. 9/11 patients (82%) with ganglioglioma (GGL) or dysembryoplastic (DNET) tumours were seizure free (8 (73%) sustained seizure freedom). 16/19 patients (84%) with cavernous haemangiomas (CAH) were seizure free (all sustained seizure freedom). 11/37 patients (30%) with malformations of cortical development became seizure free (10 (27.0%)) with sustained seizure freedom). 7/32 patients (22%) who had only gliosis became seizure free (6 (18.8%) sustained seizure freedom). Conclusion: Two years after surgery 45% of the 128 patients who had frontal lobe resections in Sweden 19902009 were seizure free, and 84%
Medical Therapy and Pharmacology 8 Wednesday, 03 October 2012

p639 LACOSAMIDE AS ADD-ON TO MONOTHERAPY IN PATIENTS WITH PARTIAL-ONSET SEIZURES: INTERIM RESULTS OF THE POST-MARKETING VITOBA STUDY (VIMPAT ADDED TO ONE BASELINE AED) M. Noack-Rink*, T. Mayer, S. Arnold, T. Kumke*, and U. Runge *UCB Pharma GmbH, Monheim, Germany; Schsisches Epilepsiezentrum, Radeberg, Germany; Neurozentrum Nymphenburg, Mnchen, Germany; and Neurologische Universittsklinik, Greifswald, Germany
Purpose: To evaluate the efficacy and safety of lacosamide when added to a single antiepileptic drug (AED) in adult patients with focal epilepsy.
186 Abstracts
Method: Six-month prospective, non-interventional study with a planned enrollment of 500 patients. Result: Efficacy data are available for 99 patients and safety data for 109. Patients were less refractory than those in the pivotal Phase II/III trials. Over the final three months of the evaluation period, 77.8% and 64.6% of patients experienced a 50% and 75% reduction in seizure frequency and 43.4% were seizure-free (median dose 200mg). Patients with a history of one lifetime AED experienced greater benefit with lacosamide than the overall population: 86.7% and 80.0% showed a 50% and 75% reduction in seizure frequency, respectively; 66.7% were seizurefree. When analyzed by concomitant AED, a trend towards greater improvement was observed in patients taking non-sodium channel blockers compared with those taking SCBs: 50% and 75% responder rates were 83.0% and 72.3%, respectively, versus 73.1% and 57.7%; seizurefree status was 46.8% versus 40.4%. Physicians judged symptoms in 23.2% and 40.4% of patients as very much improved or much improved. TEAE incidence (50.5%) was lower than in the pooled pivotal trials (81.0% for all doses). The most common TEAEs (5%) were fatigue, dizziness and convulsion. Conclusion: Patients with less refractory disease treated with lacosamide as add-on to monotherapy derived therapeutic benefits that exceed those observed in the pivotal trials. Patients on concomitant nonSCBs also tended to show better responses to lacosamide than those on SCBs. Sponsored by UCB Pharma
p641 ESLICARBAZEPINE USE IN MENTALLY RETARDED AND REFRACTORY EPILEPTIC PATIENTS A. Fraile, P. E. Bermejo, J. Chamorro, and E. Blanco Fundacin San Jose, Madrid, Spain
Purpose: Despite the introduction of multiple new antiepileptic drugs (AEDs) in the past 20 years, about 30% of patients with epilepsy continue to experience uncontrolled seizures or significant side effects. This resistance to treatment is even higher in people with mental retardation. The aim of this study is to present our experience with eslicarbazepine therapy in mentally retarded and refractory epileptic patients. Method: This is a retrospective study and we reviewed the medical charts of all mentally retarded patients receiving oral eslicarbazepine until February 2012. Efficacy was determined according the seizure frequency during the month prior to treatment initiation and the month after the maximal dosage of eslicarbazepine was attained. Result: Twenty eight patients (13 men and 15 women) aged 1761 (mean 26.112.1) years were enrolled. Twelve suffered perinatal anoxia, seven had epilepsy attributed to a structural cause, six had epilepsy of unknown cause, and three had Lennox-Gastaut syndrome. The mean number of AEDs they were taking was 2.30.8 and the previous AEDs they had tried were 7.92.2. The mean follow-up was 4.12.2 months. Seven (25%) patients had at least a 50% seizure reduction, while a small decrease was obtained in another nine (32%). It was discontinued in six (21%) patients because of inefficacy. Side effects were reported in eight (28%) patients. Conclusion: Eslicarbazepine seems to be effective and safe in mentally retarded and refractory epileptic patients according to our cohort. Further prospective studies on eslicarbazepine efficacy and safety in a large number of this type of patients are warranted.
p640 CHRONIC VALPROATE ENCEPHALOPATHY WITH REVERSIBLE COGNITIVE IMPAIRMENT AND BRAIN ATROPHY A. G. Caicoya, R. Yubero, M. Jimnez De La Pea, S. GilRobles, and R. Arroyo Hospital Universitario Quirn Madrid, Madrid, Spain
Purpose: Chronic valproate encephalopathy causes a gradual cognitive decline that may easily be overlooked. Reversible brain atrophy caused by valproate has been reported in children and young adults, but just in one case in an older patient (Thirugnanasampanthan et al., Gen Hosp Psychiatry 2006;28:458462). Method: We report two cases of adults under prolonged valproate treatment showing cognitive slowing and diffuse brain atrophy, being both conditions reversible after withdrawal of valproate. Result: A 52 year-old male with treatment-resistant epilepsy on valproate (for about 30 years), clobazam and zonisamide was admitted for epilepsy surgery evaluation. Video-EEG monitoring showed complex partial seizures of right temporal origin and slight slowing of background activity. Neuropsychological assessment revealed a generalized cognitive decline with slowing of speech and information processing. The cranial MRI showed diffuse brain atrophy. Chronic valproate encephalopathy was suspected, and valproate progressively withdrawn. The work-up one year later showed an important recovery of the brain atrophy and improvement of cognitive functions in the neuropsychological assessment. The other case of chronic valproate encephalopathy was observed in a 55 years-old female with partial epilepsy, on valproate for about seven years. She complained about dizziness and cognitive slowing. The EEG showed a left temporal delta focus and frontal bilateral synchronous spike-wave complexes. After complete withdrawal of valproate she showed an important improvement of her cognitive processing speed and brain atrophy. Conclusion: Patients with cognitive decline and chronic treatment with valproic acid should always receive a neuroimaging and neuropsychological work-up, in order to identify remediable iatrogenic adverse effects.
p642 VAGUS NERVE STIMULATION FOR DRUG RESISTANT EPILEPSY IN CHILDREN: GAZI UNIVERSITY EXPERIENCE A. Serdaroglu*, E. Arhan, G. Kurt*, E. Bilir*, K. Baykaner*, A. Erdem*, and E. Durdag* *Gazi University School of Medicine, Turkey; and The Ministry of Health, Ankara Children's Health and Diseases HematologyOncology, Education and Research Hospital, Turkey
Purpose: Vagus nerve stimulation (VNS) is an alternative treatment for patients with drug-resistant epilepsy who are not candidates for resective surgery. VNS has been demonstrated to be efficacious, safe. The aim of this study was to evaluate the experience of VNS at the Gazi University, and to examine demographic data, types of seizures, and seizure-control outcomes among treated subjects. This is the first account of VNS in a pediatric population in Turkey. Method: Sixty-three children under eighteen years of age with drugresistant epilepsy were implanted with a vagus nerve stimulator device May 2000 and November 2011. Result: The patients mean age at vagus nerve stimulator implantation was 10.923.41 years. The most common type of seizure was secondary generalized tonic-clonic. All the patients seizure were drug-resistant and all had been treated with an average of 42 drugs. Follow-up was complete for 92.07% of patients and the mean duration of VNS therapy in these patients was 49.2532.20 months. Seizure frequency significantly improved with VNS therapy (mean reduction 53.17%) without a significant reduction in antiepileptic medication burden. Reduction in seizure frequency of at least 50% occurred in 39.7% of patients and 17.5% of patients experienced at least a 75% reduction. Three patients were sei-
187 Abstracts
zure-free. Ten patients experienced stimulation-induced symptoms, but did not require device remova. One patient experienced a wound infection twice and VNS device had to be removed. Three patients died because of reasons not related to VNS implantation, one pneumonia, one sepsis and one sudden death in epilepsy (SUDEP). gine became seizure free. In a multivariate model the following variables were significant predictors of response to lamotrigine: use of sodium channel blocker, use of valproate, number of antiepileptic drugs used, and age. Levetiracetam was effective in 54% of patients and 23% of patients using levetiracetam became seizure free. In a multivariate model the following variables were significant predictors of response to levetiracetam: epilepsy duration, use of carbamazepine, and history of psychiatric disease. Conclusion: Lamotrigine and levetiracetam are effective drugs in clinical practice. Several clinical variables were identified as predictors of response to lamotrigine and/or to levetiracetam.
p643 EXPERIENCE WITH LACOSAMIDE IN A SERIES OF ADULTS WITH DRUG-RESISTANT FOCAL EPILEPSY A. Verentzioti*, A. Siatouni, and S. Gatzonis *Evaggelismos Hospital, Athens, Greece; and Athens Medical School, Athens, Greece
Purpose: To evaluate the efficacy and safety of lacosamide (LCM) as adjunctive therapy in patients with refractory focal epilepsy. Method: A retrospective study of patients suffering from severe pharmacoresistant partial epilepsy with or without secondary generalization from 2008 until 1/12/2011. Result: 92 patients (52 men and 40 women) were included in this study. The mean age is 33 years (1284) and the mean age of seizure start is 13 years (183). Prior to the LCM administration, patients had received 3 antiepileptic drugs. The mean dosage of LCM was 300 mg/ day (range 100600 mg/d). The mean seizure rate was 13 monthly before and 9 monthly after LCM administration (Wilcoxon Signed Ranks Test: -4,014, Sign Test: -4,396). 16 patients (17, 3%) are seizure free. Reduction of frequency was reported by 29 (31, 5%) patients (<25%:3, 2550%: 6, 5075%: 10, >75%: 10). 18 patients (25, 3%) had no significant improvement. Twenty-eight patients (30, 4%) reported drug-related adverse events (AEs); the most common was dizziness, double vision and ataxia (21, 439, 3%). There were no serious AEs. Conclusion: Adjunctive lacosamide significantly reduced seizure frequency in patients with severe uncontrolled partial seizures without severe adverse events.
p645 COSTS, WORK ABSENCE, AND ADHERENCE IN PATIENTS WITH PARTIAL ONSET SEIZURES TAKING GABAPENTIN OR PREGABALIN D. Labiner*, N. L. Kleinman, A. Sadosky, J. Seid, and R. Martin *University of Arizona, Tucson, AZ, USA; HCMS Group, Cheyenne, WY, USA; Pfizer, Inc., New York, NY, USA; and University of Alabama at Birmingham, Birmingham, AL, USA
Purpose: Few studies have examined the burden of epileptic partial onset seizures (POS) from the employer perspective or compared users of gabapentin and pregabalin in the treatment of POS. This study compares pharmacotherapy and resource utilization of patients with POS newly treated with gabapentin or pregabalin. Method: Retrospective data from employees and dependent spouses with POS starting treatment (index date) with either gabapentin or pregabalin were analyzed. At least 6 months of health plan enrollment pre- and post-index were required. Regression modeling compared medical and prescription costs, sick leave, short-term disability, and workers compensation costs, and absence days during the 6-month post-index period. Persistence, adherence (percent of days covered), and the impact of copay and copay as a percent of salary on adherence were modeled. Result: All costs were statistically similar between the gabapentin and pregabalin cohorts except drug costs (44% higher in the pregabalin cohort, P=0.01). Sick leave days, however, were lower in the pregabalin cohort than in the gabapentin cohort (P=0.04). Adherence was greater in the pregabalin cohort (P=0.05) as was persistence, although the latter was not significant. Adherence decreased as copay or copay as a percent of salary increased beyond specific levels in both cohorts. Conclusion: Cost, work absence, and medication persistence and adherence outcomes associated with gabapentin and pregabalin were found to be similar in most cases. Even when not significantly different, most outcomes favored pregabalin. The impact of POS on patients and on employer sponsors is substantial across a variety of metrics.
p644 EFFECTIVENESS OF LAMOTRIGINE AND LEVETIRACETAM IN CLINICAL PRATICE: RETROSPECTIVE CHART REVIEW C. Deckers*, A. Beun, G. De Haan, H. Van Hemert-Van Der Poel*, and J. Van Der Palen *SEIN, Zwolle, The Netherlands; SEIN, Heemstede, The Netherlands; and Medisch Spectrum Twente, Enschede, The Netherlands
Purpose: Evaluation of the effectiveness of lamotrigine and levetiracetam in a hospital-based cohort of epilepsy patients with localizationrelated epilepsy. Method: Medical charts of patients treated at SEIN epilepsy centre were reviewed. Effectiveness of lamotrigine and/or levetiracetam therapy in patients who were prescribed these drugs because of insufficient seizure control was assessed during the first year of use, with patients serving as their own controls. Effectiveness was determined by reduction in seizure frequency. Result: Effectiveness could be assessed in 174 patients using lamotrigine and 154 patients using levetiracetam; assessment in remaining patients was not possible due to various reasons, such as insufficient data on seizure frequency. Lamotrigine was effective (i.e. >50% reduction in seizure frequency) in 48% of patients and 16% of patients using lamotri-
p646 INCREASED LEVETIRACETAM CLEARANCE IN PREGNANCY: IS SEIZURE FREQUENCY AFFECTED? E. Mawhinney*, A. I. Hoeritzauer, B. Irwin*, S. Hunt*, J. Morrow*, and J. Craig* *Royal Victoria Hospital, Belfast, UK; and NHS, UK
Purpose: Background: Emerging data on the teratogenic potential of valproate and topiramate have resulted in a prescribing shift towards lamotrigine and levetiracetam in women of childbearing age with epilepsy. However use of these AEDs during pregnancy is associated with new difficulties. It is widely documented that lamotrigine clearance
188 Abstracts
increases by up to 330% in pregnancy, with associated increase in seizure frequency in 39- 45% of women. Early studies show that levetiracetam serum levels also fall by 40- 62% during pregnancy, but in contrast to lamotrigine very little is known about the clinical effect of this observation. Method: Retrospective chart review was performed for women in Northern Ireland taking levetiracetam monotherapy during pregnancy from 2003 to 2011. Result: Forty four women taking levetiracetam during pregnancy were identified. Deterioration or relapse of seizures was observed in 30.8% of women, improvement in seizure control in 17.9% and no change in 51.3%. Conclusion: Seizure control deteriorated in over 30% of women in this study, towards the upper end of the expected range of 14- 32%. This is the largest study to date of seizure control in women taking levetiracetam during pregnancy. These preliminary findings, together with the paucity of evidence in this area, highlight that further research is clearly needed to guide clinicians on the potential clinical impact of this phenomenon. Method: Adult patients who had been treated with pregabaline as a subgroup of Seoul Epilepsy Registry Cohort were recruited. We obtained the information about timing of medication and checked the serum drug level. Electronic medical records were retrospectively reviewed. Efficacy was measured using a five point scale. Result: Of total 1338 patients in Seoul Epilepsy Registry, 119 patients were prescribed pregabaline. The 72 patients were male and mean age was 42.44 year-old. Mean dose of pregabaline was 296.75mg per day. For 116 patients with polytherapy, mean 2.45 kinds of other antiepileptic drugs were also received. Median sample time was 6.5 hours after medication. Mean serum level of drug was 2807mg/dL. The serum level of pregabalin showed linear kinetics with daily dose and inversed correlation with median sample time. Although the 75% seizure reduction rate was 89.1%, there was no correlation between drug level and seizure control. Conclusion: We successfully checked the therapeutic pregabalin levels. The further study about other factors that could affects drug levels, such as drug-drug interaction and genetic variation, is needed.
p647 RETENTION OF LACOSAMIDE IN AN THIRD-LINE REFERRAL EPILEPSY CENTRE E. V. Van Beijeren, I. Vandesteenkiste, T. Punte, and G. De Haan Stichting Epilepsie Instellingen Nederland (SEIN), Heemstede, The Netherlands
Purpose: In order to determine the potential value of lacosamide for the everyday treatment of epilepsy we examined the retention of the drug in the outpatient population of our third-line referral epilepsy centre. Some reports indicate that treatment emerging adverse effects may be more frequent in patients using sodium-blocking comedication. Method: A retrospective, observational study of the first 240 outpatients that have been treated with lacosamide since March 2009. Information was retrieved from the medical records about type and frequency of seizures, epilepsy syndrome, comedication and medication history, start date of lacosamide, target dose, effects and adverse effects, and date and reason for withdrawal of lacosamide. Result: Data of 212 patients were analysed. After one year follow up retention rate was 66%. Retention did not differ between patients with or without sodium-blocking comedication. Reasons for discontinuation were: no effect (42%), adverse effects (25%) or a combination of both (42%). A positive effect of Lacosamide was reported in 58% of this refractory population. One patient became seizure free. Patients reaching higher maximum dosages were less likely to discontinue LCM. Conclusion: In a population of patients with medically refractory epilepsy retention rate for LCM is higher or comparable with other recently introduced antiepileptic medication, and is not dependent on type of comedication.
p649 HYPOTHERMIA IN TWO PATIENTS WITH REFRACTORY EPILEPSY J. Raymackers*, P. Jacquerye*, A. Melin, F. Dupuis*, F. Linard, F. Evrard*, G. Picard*, K. Van Rijckevorsel, and M. J. Dupuis* *Clinique Saint-Pierre, Ottignies, Belgium; CHC Clinique St-Joseph, Lige, Belgium; and Centre Neurologique William Lennox, Reference Center for Refractory Epilepsy, Universit Catholique de Louvain, Louvain-la-Neuve, Belgium
Purpose: To draw attention of clinicians to the possible relationship between hypothermia and use of antiepileptic drugs. Method: We report two cases of patients admitted to a general hospital because of severe apathia associated with probable drug-induced hypothermia. Result: A 43-year-old male patient presented with gait alteration. He was suffering from congenital encephalopathy, mental retardation, psychiatric disorder and refractory epilepsy. At the emergency room, he showed altered conscience, without neurological or infectious signs. Axillar and rectal temperatures were noted 31C and 30C, respectively. Axillar temperature further decreased to 29C. The patient was receiving several medications, including antiepileptic drugs VPA, OXC and TPM, the latter being only recently added. After cessation of TPM, temperature progressively returned to normal values. A 46-year-old female patient developed apathy, anorexia, hypotension, slight blood oxygen desaturation and 36C hypothermia. She was receiving LEV, GBP, VPA and LTG for refractory seizures secondary to severe perinatal anoxic encephalopathy. One week prior to admission, daily dose of LTG was erroneously doubled. This coincided with the alteration of mental and motor functions. The day of admission, axillar temperature was 33.5C. Ancillary tests were of little contribution except for a chest X-Ray which disclosed right lobar density. Intravenous antibiotherapy was started and initial regimen of LTG was given. Temperature normalization and clinical improvement were quickly noted. Conclusion: Several AEDs were suspected to induce hypothermia, including VPA and GBP. TPM was suspected to enhance VPA effect on hypothermia, while LTG was never mentioned. This report suggests that LTG, as well as TPM, may elicit hypothermia in patients on polytherapy. Clinicians treating such patients should therefore be aware of this treatable side-effect.
p648 THE EXPERIENCE OF THERAPEUTIC NEW ANTIEPILPTIC DRUG MONITORING (PREGABALINE) IN THE TERTIARY EPILEPSY CENTER J. Byun, B. S. Kang, J. Lim, B. S. Park, J. W. Shin, Y. S. Kim, K. Chu, and S. K. Lee Seoul National University Hospital, Seoul, Korea
Purpose: We tried to evaluate the kinetics of pregabaline and correlation between serum level and seizure control in epilepsy patients in the tertiary epilepsy center.
189 Abstracts

p650 VIGABATRIN ASSOCIATED MOVEMENT DISORDER WITH MRI SCAN CHANGES: AN UNDER-RECOGNISED COMPLICATION M. Kaliakatsos, Y. A. Hernandez Vega, J. U-King-Im, K. Lascelles, and M. Lim Evelina Children's Hospital, London, UK
Purpose: To present a case report demonstrating a rare, harmful but reversible side effect of Vigabatrin. Method: Video-case report Result: A 10-month-old girl who was on treatment for infantile spasms with Vigabatrin and Tetracosactide (day 16 of treatment) presented with progressive lethargy followed by movement disorder, loss of oral feeding skills and left hemiparesis. Her spasms had stopped on day 7 of treatment. Magnetic Resonance Imaging (MRI) on Day 12 of treatment showed signal change within the basal ganglia and brainstem. Repeat MRI scan (Day 16) showed progressive signal change in the deep grey structures with a GABA peak on MRS and a further EEG showed a grossly encephalophatic but no longer hypsarrthmic pattern. A rapidly progressive mitochondrial cytopathy was considered but all neurometabolic investigations including plasma and CSF lactate and muscle respiratory chain enzyme analysis were negative. Vigabatrin was stopped on the day 22 of treatment. Over the next few days she started to make a dramatic recovery. She became more responsive, the abnormal movements stopped and the left hemiparesis recovered. Another EEG was done 24h after stopping Vigabatrin showing a significant improvement. An interval MRI done three months later was normal. Conclusion: Clinicians treating children with Vigabatrin need to be aware that encephalopathy with severe movement disorder and accompanying MRI abnormalities is a potential complication, as not only is this reversible on stopping VBT but failure to do so could lead to the diagnosis of a neurodegenerative disorder.
not differ between the groups. Comparing the VPA with OXC therapy, VPA was associated with higher activation rates of neutrophils and MDA levels. The serum MDA level was higher in the patients taking antiepileptic drugs (AEDs) than pretreatment (P=0.001) and positively correlated with the activation rates of neutrophils. Conclusion: Epileptic children exposed to oxidative stress and AEDs change the oxidative/antioxidative balance. AEDs may activate the neutrophils of patients and cause oxidative damage.
p652 EXTERNAL TRIGEMINAL NERVE STIMULATION (ETNS) FOR THE TREATMENT OF DRUG RESISTANT EPILEPSY: A PHASE II RANDOMIZED CONTROL TRIAL C. Degiorgio*, C. Kealey, J. Soss*, D. Murray*, S. Oviedo, D. Markovic*, I. Cook*, and C. Heck *University of California Los Angeles, Los Angeles, CA, USA; NeuroSigma Inc., Los Angeles, CA, USA; and University of Southern California, Los Angeles, CA, USA
Purpose: External Trigeminal Nerve Stimulation (eTNS) is a novel emerging neuromodulation therapy under investigation for the treatment of drug resistant epilepsy (DRE) and major depression (MDD). We present results from the Phase II randomized double-blind control trial of eTNS for DRE. Method: 50 subjects with DRE were enrolled at two clinical sites (UCLA and USC) and randomized to receive active eTNS or a control regimen. Baseline seizure frequency and mood were assessed prior to initiating treatment. Subjects were evaluated at 6, 12, and 18 weeks for changes in seizure frequency and mood. Result: 40.5% of subjects receiving active eTNS experienced a 50% reduction in seizure frequency vs. 15.6% of patients in the active control at 18-weeks (within group p = 0.02, between groups p = 0.078, GEE). Median seizure frequency was also significantly decreased at 12 weeks, (p = 0.013 at 12 weeks, Wilcoxon signed-rank test). Mood (Beck Depression Inventory) improved significantly from baseline during the acute treatment period (-8.1 in the treatment group vs. -3.3 in the controls (p = 0.02, ANOVA). Conclusion: In this phase II randomized control trial, eTNS was associated with a significant increase in 50% responder rate and significant improvement in mood over the 18-week acute treatment period. The robust response in both seizures and mood over the treatment period indicates that eTNS is a promising and unique new neuromodulation treatment modality.
p651 EFFECTS OF VALPROATE AND OXCARBAZEPINE ON NEUTROPHILS OXIDATIVE METABOLISM AND OXIDATIVE STRESS IN EPILEPTIC CHILDREN Y. Zhang, Y. Wang, M. Zhang, and X. Zhu Children's Hospital of Fudan University, Shanghai, China
Purpose: This study was carried out to determine the effects of valproate (VPA) and oxcarbazepine (OXC) on neutrophils oxidative metabolism and oxidant status in epileptic children. Method: We enrolled 26 patients receiving VPA, 11 receiving OXC and 30 sex-and age-matched healthy children. We measured the activation rates of neutrophils by flow cytometry and the serum activities of myeloperoxidase (MPO) in patients before and after 6 months treatment respectively and in all the healthy children. Malondialdehyde (MDA) as an indicator of lipid peroxidation and antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were also measured in plasma respectively. Result: The activation rates of neutrophils in patients treated with VPA or OXC after 6 months were significantly higher than the data of control group (P=0.001 and P=0.003, respectively) and pretreatment (P=0.001 and P=0.005, respectively). The plasma MPO activities and levels of MDA in patients were also higher while the activities of SOD and CAT were lower than the control group and pretreatment. GSH-Px levels did
p653 CLINICAL PROFILES AND OUTCOME OF PATIENTS WITH ANTIEPILEPTIC DRUG-INDUCED STEVEN JOHNSON SYNDROME/TOXIC EPIDERMAL NECROSIS G. V. L. Hamoy Philippine General Hospital, Ermita, Manila, Philippines
Purpose: This study aims to identify the epidemiological features of AED-induced SJS/TEN among patients admitted at a tertiary hospital. Specifically, the researchers wanted to describe the clinical profiles of AED-induced SJS/TEN patients; identify the antiepileptic drugs that commonly cause SJS/TEN; and to determine the outcome of patients who developed the said condition.
190 Abstracts
Method: A retrospective review of the cases seen at at a tertiary hospital, with a diagnosis of Steven Johnson Syndrome (SJS) and Toxic Epidermal Necrosis (TEN) during 2002 to 2011 was carried out. A total of 165 patients were identified with a discharge diagnosis of SJS and TEN according to International Classification of Disease code. Of these, 25 patients were selected based on the inclusion criteria of patients who developed antiepileptic dug induced SJS/TEN. The diagnosis of SJS/ TEN was based on the findings and diagnosis by dermatologist or allergologist. Presence of other pre-existing dermatologic problems such as acneiform growths, seborrheic keratosis, psoriasis, fungal or any superimposed bacterial infections were excluded in this study. The following data were obtained: age, sex, antiepileptic drugs used, dosages and duration of intake, co-medications, co-morbidities, treatment and outcome. In this study, we described the population based on the demographic profile collected. Descriptive statistics such as the mean was used for continuous data. On the other hand, frequency was used for categorical data. This study is based on a retrospective analysis. Result: This study reviewed 165 patients who developed Steven Johnson Syndrome and Toxic Epidermal Necrosis with ages ranging from 1 to 72 years old. Of these, 25 out of 165 (15%) reported intake of antiepileptic drugs, and were included in the study. Out of 25, twenty four patients (96%) developed SJS and only one developed TEN (0.04%). There were 14 (56%) men and 11 (44%) women included in the study. The mean age at diagnosis was 30 years old. Majority of the patients were adults comprising 72% and 28% were pediatric patients. Figure 1 shows that among all the patients included in the study, the most common antiepileptic drugs reported were phenytoin (9 cases, 36%) and Phenobarbital (9 cases, 36%). This was followed by carbamazepine (6 cases, 24%), Levetiracetam (2 cases, 8%), and valproic acid (1 case, 4%). In the adult group, the most common AED used was PHT, while in pediatric group, the most common was PHB. Majority of the patients (22 of 25, 88%) were on monotherapy, and three patients were given co-medication with a second antiepileptic drug. The mean duration of intake differed between antiepileptic drugs used. For PHB, the mean duration of intake was 23 days, while PHT, CBZ, LEV and VPA were 21 days, 19 days, 63 days and 7 days respectively. On the other hand, the mean duration of intake in polytherapy was 25 days. The earliest time of drug reaction developed after 7 days of intake while the longest was in 60 days. Most of the patients were treated with intravenous corticosteroids. Twenty- two patients improved from the illness, 2 died of sepsis and 1 died of renal failure. These three patients had complications while admitted. Two of them developed sepsis and one had multiple electrolyte imbalances. There were six patients who had other concomitant drugs used during the time they developed SJS and TEN. Conclusion: We concluded that PHT and PHB are the common AEDs associated with the development of SJS/TEN among patients seen in a tertiary hospital. However, in common practice in this tertiary hospital, PHB is widely used AED among adult and pediatric patients. Most of the patients who developed AED induced SJS/TEN were middle aged males. One major drawback of this study was the small population of patients with AED-induced SJS and TEN. Because of this limitation, we were not able to do a multivariable correlation of the risk factors for the AEDinduced SJS/TEN. Also the small sample size was not enough to generalize the results to the population of Filipinos taking AEDs for the first time. Result: The Consensus includes four parts: 1, Classification of seizures after cranio-cerebral diseases and trauma (CCDT) operations and general principles of treatment; 2, CCDT patients without seizure before operation: (1) Indications, methods and duration of using AEDs to prevent seizures after surgery, (2) Treatment of occurred seizures after operation with AEDs; 3, CCDT patients who had seizures before operation (the operation is for treating other brain disease, focal lesions other than epilepsy): methods and duration of using AEDS after operation; 4, Emergency treatment of seizures (GTCS and/or convulsive status epilepticus) after cranio-cerebral operation. A flow chart for the above-mentioned is tabled in the present paper. Conclusion: The Consensus on Using AEDs after Cranio-cerebral Operation has been completed this year to serve as a reference document for neurosurgeons and neurologists, pediatricians who are dealing with epilepsy treatment for CCDT patients after brain surgery.
p655 THE COMPARISION OF EEG PATTERNS AT THE BACKGROUND OF AEP DRUGS IN EPILEPTIC PATIENTS I. Khachidze, V. Maloletnev, and M. Gugushvili Beritashvili Centre of Experimental Biomedicine and Tatishvili Medical Center, Tbilisi, Georgia
Purpose: Electroencephalography (EEG) is an efficient tool to study both benefit and a potential adverse effect of various antiepileptic drugs. Although selection of antiepileptic drugs (AED) depends on type of seizures, the general effect of various AED on overall neurophysiological state of CNS is not fully understood. The aim of this study was to assess the effect of Carbamazepine (CBZ) and Vallproate acid (VPA) on both an epileptic activity and a general brain activity in epileptic children using EEG technique. Method: One hyndred and seventeen epileptic patients between 5 and 11 years old were examined. Some patients (n=63) received VPA treatment, whereas others (n=54) CBZ therapy. The patients underwent EEG recording three times: before administration of AED, 34 months and 6 8 months after the initiation of treatment. The Spectral analysis of the absolute value of power (AVP) was a studied variable. Results: VPA reduced the degree of disorganization of basic EEG rhythmicity of high amplitude mono-poly-morph waves in low frequency range, suppressed a spike-wave complex in thalamus and decreased AVP spectra especially in parietal cortex. On the other hand, CBZ therapy increased AVP dynamics by increasing activity in the low frequency range. CBZ mostly affect the neural population of the cortex and predominantly occipital cortical areas. Conclusion: The different effect of VPA and CBZ on the bioelectrical activity of the brain in epileptic children could be related to the regionspecific differences within the loci of maximal neuropharmacological effect of the studied drugs.
p654 THE CONSENSUS ON USING AEDS AFTER CRANIOCEREBRAL OPERATION S. Li China Association against Epilepsy, Beijing, China
Purpose: Trying to set up commonly recognized regulation of using AEDs after the Cranio-cerebral operation to prevent, control of seizures. Method: The China Association Against Epilepsy (CAAE) organized a taskforce to compile the The Consensus on Using AEDs after Craniocerebral Operationand accepted by the CAAE Board in 2012.
p656 EFFICACY AND SAFETY OF ONCE-DAILY ADJUNCTIVE PERAMPANEL, A SELECTIVE AMPA ANTAGONIST: A POOLED ANALYSIS OF THREE PHASE III TRIALS IN PATIENTS WITH TREATMENT-RESISTANT PARTIAL-ONSET SEIZURES E. Ben-Menachem*, G. L. Krauss, S. Noachtar, J. M. Serratosa, D. Squillacote, H. Yang, J. Zhu, and A. Laurenza *University of Gothenburg, Gothenburg, Sweden; Johns Hopkins University, Baltimore, MD, USA; University of
191 Abstracts
Munich, Munich, Germany; Hospital Universitario Fundacin Jimnez Diaz and CIBERER, Madrid, Spain; and Eisai Neuroscience Product Creation Unit, Woodcliff Lake, NJ, USA
Purpose: Perampanel was evaluated in three pivotal phase III trials. Results from the separate trials have been presented previously; here, we analyzed the pooled efficacy and safety results across the three studies according to the actual doses of perampanel achieved. Method: Patients (12 years with uncontrolled partial-onset seizures) were randomized to double-blind placebo, perampanel 2, 4, 8, 12 mg/day. Percent change in seizure frequency/28 days and 50% responder rate were primary endpoints. Efficacy analyses in this report were based on actual (last) doses received at the end of the double-blind phase by completer patients (excluding Central/South American patients due to significant treatment-by-region interactions). Safety analyses included all treated patients who had safety assessments. Result: Overall, 442, 180, 172, 431, and 255 patients were included in the safety population for placebo, perampanel 2, 4, 8, 12 mg (randomized dose), respectively. 348, 161, 159, 46, 287, 14, 114 patients completed the study on a last dose of placebo, perampanel 2, 4, 6, 8, 10, 12 mg. Median percent changes in seizure frequency for placebo, 2, 4, 8, 12 mg were -11.7%, -17.3%, -24.1%, -31.9%, -26.2%, respectively. Responder rates were 18.4%, 22.4%, 30.8%, 37.6%, and 39.5%. These data are comparable with randomized results from the individual studies, which did not account for failure to reach assigned doses. Safety analyses were also comparable. Conclusion: Perampanel efficacy and safety are further demonstrated in actual dose analyses of the entire phase III program population. Support: Eisai Inc Conclusion: LEV was more effective in the treatment of partial seizures compared with generalized. LEV was well tolerated by our patients.
p658 A NOVEL ANTICONVULSANT ISOXYLITONES [E/Z] SUPPRESSES SODIUM CURRENTS IN NAV1.2 AND NAV1.3, AND PROLONGS INACTIVATION DEVELOPMENT AND RECOVERY FROM INACTIVATION IN VOLTAGE-GATED SODIUM CHANNELS M. N. Ashraf*, S. U. Simjee, and M. O. Poulter* *Robarts Research Institute, London, ON, Canada; and International Center for Chemical and Biological Sciences, Karachi, Pakistan
Purpose: Epilepsy remains a major medical challenge and till to date is not completely curable and more than 30% patients worldwide are still living with refractory epilepsy. The roots of the plant Delphinium denudatum indigenous to the Himalayas and Kashmir had been reported to be used in treating seizures by local folk medicine practitioners. Although, the extracts / fractions prepared from the aforementioned plant have been previously studied in acute seizure models, the purified, patented compound (Patent No. 7,399,888 B2) named Isoxylitones ([E/Z]-2-propanone-1,3,5,5-trimethyl2-cyclohexen-1-ylidine) have not been characterized for its mechanism of action. Method: We have carried out patch clamp and electrophysiology studies in order to explore the mechanism of action and doseresponse curve of this novel anticonvulsant compound both in vitro and in vivo. Result: Voltage-clamp studies showed that isoxylitones suppressed sodium current (INa) in Nav1.3 in a concentration-dependent manner with IC50 value of 185 nM in cultured rat cortical neurons (pyramidal and interneurons). The presence of 185 nM isoxylitones not only prolonged the recovery of sodium channels from inactivation with the time constant s 18.7 ms as compared to control recordings with s 9.4 ms, but also significantly altered the voltage dependence of inactivation development by shifting the Boltzmann sigmoidal curve to the more hyperpolarized potentials. Moreover, isoxylitones inhibited INa in Nav 1.2 with IC50 values of 185 nM and 200 nM in naive and electrically kindled cortical neurons in rat brain slices, respectively. Conclusion: Thus, isoxylitones is now a potential candidate to be developed as a future anti-epileptic drug (AED).
p657 EFFECTIVENESS AND TOLERABILITY OF LEVETIRACETAM IN CHILDREN UNDER 2 YEARS OF AGE G. A. Ramos-Rivera, M. Kolnikova, A. Blahova-Vicenova, D. Kovarova, J. Payerova, and P. Sykora Childrens University Hospital, Bratislava, Slovak Republic
Purpose: To assess the effectiveness and tolerability of levetiracetam (LEV) as add-on therapy in the treatment of epilepsy in children less than 2 years of age. Method: Retrospective evaluation of treatment with LEV in a cohort of 26 children aged 222 months (mean 11.7 months). Treatment was considered effective if the reduction of seizures reached 50%. The group consisted of children hospitalized and followed-up in the Department of Pediatric Neurology in Childrens University Hospital in Bratislava from January 2009 to December 2011. The mean dose of LEV was 37.3 mg/ kg/d (range 16.550.0 mg/kg/d), the average number of antiepileptic drugs used before LEV was 2.1 (16 drugs). Mean follow-up time was 7.8 months (range 0.126.0 months). Result: Of the 26 children, LEV was effective in 7 patients (26.9%), two of whom were seizure-free (8.7%). LEV was ineffective in 15 children (57.7%) and in one patient (4.4%) the number of seizures increased. Generalized seizures were present in 10 patients (38.5%). In two of them LEV was effective (20.0%). Partial seizures occurred in 17 patients (43.5%). LEV was effective in 6 of these children (35.3%). Two patients of the whole cohort present both partial and generalized seizures. No effect was observed in one patient with reflex atonic seizures, one child with epilepsia partialis continua and one with malignant migrating epilepsy. LEV was discontinued for adverse reactions in 3 children (11.5%).
p659 EFFICACY OF DIFFERENT LAMOTRIGINE DOSAGE REGIMENS IN EPILEPETIC PATIENTS CLINICAL EXPERIENCE R. Gilad E Wolfson Med Center, Holon, Israel
Purpose: Lamotrigine is an effective and rather innocuous drug used in a large spectrum of epileptic disorders for monotherapy. Yet the optimal dose of lamotrigine when given as monotherapy has still to be determined. In pivotal studies, the daily dose recommended is 200 mg. Clinical experience accumulated during the last two decades shows that this daily dosage is not sufficient in many cases to achieve seizure freedom. Then again, doses twice as high do not increase significantly the drug toxicity. The purpose of the present study is to evaluate the clinical outcome on a population of epileptic patients treated at first with an average daily dose of 200 mg lamotrigine and then with the range of doses needed to achieve seizure freedom, or if these patients still experience seizures, were they switched to another medication? And what was their outcome?. The study is to include evaluating the influence of real life experiences, often quite different from RCT study conclusions, and the dosage regiEpilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x
192 Abstracts
men recommended by pivotal studies for being the ideal one for this patient population. Method: This is a retrospective study monitoring the records of all the adult patients, who were treated with lamotrigine as monotherapy for seizures, at two epilepsy clinics. All these patients treated at a dosage of 200 mg for at least three months were included in the study. Data included type of seizures, disease duration, therapy duration and seizure frequency (if the patient was not seizure-free). These patients, who suffered from breakthrough seizures or had to change their AED, were categorized and statistically evaluated separately. Result: Until now, a 100 adult patients records were reviewed and almost one-half of the patients were not free of seizures while being treated with lamotrigine 200 mg per day as monotherapy. About 50% of these patients needed a higher dose of lamotrigine for stopping the seizures, and about 30%, needed to change treatment. Conclusion: It may be necessary to consider starting a daily dose higher than 200 mg of lamotrigine from the beginning, instead of having to urgently raise the dosage only after the patient experienced breakthrough seizures.
p661 ADJUNCTIVE LACOSAMIDE IN PATIENTS WITH UNCONTROLLED FOCAL EPILEPSY: INTERIM ANALYSIS OF A PROSPECTIVE AUDIT K. Kelly, L. J. Stephen, P. Parker, and M. Brodie Western Infirmary, Glasgow, UK
Purpose: This prospective audit explores outcomes with adjunctive lacosamide (LCM), a novel sodium channel blocker, in everyday clinical practice. Method: To date, 127 of 150 patients (73M; 77F, 1874 years [median 42 years]) with uncontrolled partial-onset seizures + secondary generalisation (monthly frequency 1300; [median 4]) have reached an endpoint. They received mostly one (range 14) antiepileptic drugs (AEDs), having previously tried 112 schedules (median 2). After 12 weeks on stable dosing, LCM was added and titrated as necessary. Result: Seizure freedom was achieved in 30 (24%) patients (median LCM dose 100mg/day, range 50500mg/day). Seven received LCM with sodium channel blockers, 19 with other mechanisms, and 4 controlled on LCM monotherapy. Patients were more likely to become seizure-free when LCM was used as first add-on (26 of 83, 31.3%), compared to later treatment (4 of 44, 10.3%; p=0.005). Twenty-five (19%) patients were classified as responders (>50% seizure reduction versus baseline) with 43 (34%) demonstrating marginal benefit. LCM was withdrawn in 29 (23%) patients (11 lack of efficacy, 18 side-effects). Commonest problems included nausea, vomiting, sedation, headache, diplopia, dizziness, tremor, ataxia and rash. More patients taking sodium valproate (14 of 34) discontinued LCM compared to other AEDs (20 of 102; p=0.012), particularly due to side-effects (11 of 34 on valproate vs 10 of 102 on other AEDs; p=0.002). Conclusion: Adjunctive LCM was effective and well-tolerated whatever the baseline treatment. Seizure freedom was more likely when LCM was used a first add-on. Patients taking valproate were more likely to discontinue LCM.

p660 LOW DOSE LACOSAMIDE-INDUCED ATRIAL FIBRILLATION: CASE ANALYSIS WITH LITERATURE REVIEW K. R. Kaufman, A. E. Velez, S. Wong, and R. Mani UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ, USA
Purpose: Lacosamide (LCM) is a novel anti-epileptic drug (AED) approved by the FDA for adjunctive treatment of partial epilepsy with and without secondary generalization. LCM selectively modulates voltage-gated sodium channels. AED selection is related to both efficacy and adverse effect profile. Dose-dependent LCM-induced cardiac arrhythmias have been reported. This case represents the first instance of low loading dose LCM-induced atrial fibrillation. Method: Case analysis with literature review. Result: A 67 year-old woman with a history of complex partial seizures, peri-menstrual migraines, and multiple myeloma was admitted for autologous bone marrow transplant. This patient had no known prior cardiac disease. Admission medications included methylprednisolone, clotrimazole, fluconazole, acyclovir, neupogen, ondansetron, pantoprazole, loperamide, calcium phospate, and primidone. Renal and hepatic function was normal. During her admission, episodes of staring with oral/facial automatisms increased in frequency and duration (multiple events/hour). The patient did not respond to addition of levetiracetam (1500mg bid) and continuous video-EEG was initiated to characterize her seizure activities. Multiple epileptic events were recorded within four hours on video-EEG. LCM was initiated with 200mg intravenous infusion, at the end of which an irregularly irregular rhythm was noted on telemetry. Asymptomatic atrial fibrillation lasted for two hours with spontaneous resolution. Atrial fibrillation onset correlated to the theoretical time of maximum LCM plasma concentration. LCM was discontinued. Conclusion: Low loading dose LCM may provoke atrial fibrillation. Neurologists and internists need to be cognizant of this potential adverse effect. Cardiac monitoring may be required with LCM dose rapid titration, especially if given intravenously.
p662 DIAGNOSTICS AND THERAPEUTICASPECTS OF RESISTANT EPILEPTIC SEIZURES IN CHILDREN OF EARLY AGE WITH A TUBEROUS SCLEROSIS L. G. Kirillova*, L. I. Tkachuk, A. A. Shevchenko*, V. V. Lysytsa*, and L. Y. Sylaeva* *Institute of Pediatrics, Obstetrics and Gynecology, Kiev, Ukraine; and Pediatrics, Obstetrics and Gynecology, Kiev, Ukraine
Purpose: optimization of early diagnostics and treatment of resistant epileptic attacks in children with a tuberous sclerosis. Method: During the last 7 years there were studied 9 children with a tuberous sclerosis in an age category to 3 years. On the basis of magnetic resonance tomography, for all nine children there were determined hamartomas from 3 to 30 millimetres in the different areas of the brain. There were discovered rabdomyomas in 3 children in a term 3537 weeks of pregnancy intrauterinely. In spite of focal lesions of brain structures, in all children were noticed generalized tonic-clonic seizures (resistant) from 5 to 10 a day. During the treatment of Topamax (to 10 mg/kg), frequency of attacks decreased, however, there was no control. Apart from anticonvulsants (Topamax) the children started to receive the preparation Vigabatrin (from 40 to 100 mg/kg). Result: Combination of anticonvulsive therapy led to the decrease in the number of attacks in 4 children from 1 attack in a day to 1 attack in a month. In 5 children attacks were halted.
193 Abstracts
Conclusion: This work stresses the necessity of timely magnetic resonance tomografy and combination of Topamax and Vigabatrin for optimization of treatment of resistant epileptic attacks in children with a tuberous sclerosis. Results: Showed eleveted plasma tHcy levels (tHcy > 15micromol/l) in 25 (44%) patients . Even 51 (89.5%) patients had values more than it is recommended, statistically significant in patients on polytherapy (p= 0.002) than on monotherapy. Serum FA levels were lower in 40 (70%) patients, esspecially in patients with longer duration of therapy and in those on polytherapy. Statistically significant differences for both parametars were found in patients using carbamazepin and phenobarbital than in patients using other AEDs (p< 0.005). Mean velue of vitamin B12 was normal in majoriti of patients. Our study confirmed high frequency of HHcy in epileptic-patients and suggested that carbamazepin and phenobarbital play major role in development of HHcy. Adding folate and vitamin B12 to every day AED therapy is safe way of reducing risk of HHcy.
p663 DESIGN OF AN OPEN-LABEL, MULTICENTRE, NONINTERVENTIONAL STUDY OF ZONISAMIDE AS FIRST-LINE ADJUNCTIVE TREATMENT IN ADULTS WITH PARTIAL EPILEPSY: THE ZOOM STUDY M. Baulac*, F. Rugg-Gunn, and I. Chouette *Neurology Hpital Piti-Salptrire, Paris, France; The National Hospital for Neurology and Neurosurgery, London, UK; and Eisai Europe Limited, Hatfield, UK
Purpose: Zonisamide (ZNS), a benzisoxazole derivative chemically unrelated to other antiepileptic drugs (AEDs), is currently licensed for adjunctive treatment of adults with partial seizures (with or without secondary generalisation). Whilst clinical trials of adjunctive AED therapies are required for regulatory purposes, they do not necessarily reflect real-life practice, since conducted under standardised conditions in carefully selected, highly refractory populations. The purpose of this study is to assess retention rate, efficacy and tolerability of zonisamide when used as first-line adjunctive treatment in adults with less refractory partial epilepsy, under everyday clinical practice conditions. Method: ZOnisamide in partial-onset seizures with One AED as baseline Medication (ZOOM) is a prospective, international, open-label, noninterventional study that will enrol adults with partial-onset seizures, insufficiently controlled with AED monotherapy, for whom the treating physician has decided to initiate adjunctive ZNS therapy. ZNS treatment will be commenced according to license. Patients will be seen at baseline and then according to normal clinical practice over 6-7 months. Study assessments will be conducted at baseline and after 3 and 6 months. Primary endpoint will be 6-month retention rate. Other assessments will include seizure control, adverse events and quality of life. Dosing information will also be collected. Result: The study is expected to enrol approximately 700 patients from 200-250 centres in 9 European countries. Recruitment is expected to commence March 2012; study is expected to complete end of 2013. Conclusion: ZOOM will provide valuable information on ZNS as firstline adjunctive treatment under conditions of everyday clinical practice. Supported by Eisai
p665 DESIGN OF THE EPOS STUDY: AN OPEN-LABEL, MULTICENTRE, NON-INTERVENTIONAL STUDY TO EVALUATE ESLICARBAZEPINE ACETATE AS ADJUNCTIVE TREATMENT TO ONE BASELINE ANTIEPILEPTIC DRUG IN ADULTS WITH PARTIALONSET SEIZURES M. Holtkamp*, C. Lawthom, and I. Chouette *Charit Universittsmedizin, Berlin, Germany; Aneurin Bevan Health Board, Gwent, UK; and Eisai Europe Limited, Hatfield, UK
Purpose: Eslicarbazepine acetate (ESL) is a once-daily voltage-gated sodium channel blocker that was approved in Europe in 2009 as adjunctive therapy in adults with partial-onset seizures, with or without secondary generalisation, based on an initial proof-of-concept Phase II trial and three subsequent Phase III trials. This non-interventional study aims to increase the knowledge about ESL's effectiveness and tolerability in routine clinical practice, when used to treat adult epilepsy patients who are less refractory than those included in Phase III adjunctive clinical trials. Method: The Eslicarbazepine acetate in Partial-Onset Seizures study (EPOS) is a prospective, multicentre, open-label, non-interventional study involving adults with partial-onset seizures insufficiently controlled with AED monotherapy, for whom the treating physician has previously decided it was in the patient's best interest to be initiated adjunctive ESL, according to its license and Summary of Product Characteristics. Patients will be seen at baseline and then according to normal clinical practice, over a follow-up period of 67 months. Study assessments will be conducted at baseline and after 3 and 6 months. Primary endpoint will be 6-month retention rate. Other assessments will include seizure frequency, adverse events and quality of life. Result: EPOS is expected to enrol approximately 800 patients from 200 centres in Denmark, France, Germany, Norway, Sweden and UK. Recruitment is expected to commence March 2012 and the study is expected to complete end of 2013. Conclusion: EPOS will provide a better understanding of the use of ESL as early adjunctive therapy in a clinical practice setting. Supported by Eisai
p664 HYPERHOMOCYSTEINEMIA IN EPILEPTIC PATIENTS M. Candrlic, R. Susak, and S. Juric Clinical Hospital Center Osijek, Osijek, Croatia
Purpose: Antiepileptic drugs (AEDs) may induce supraphysiological plasma concentrations of total (t) homocysteine (Hcy). Moderate hyperhomocysteinemia (HHcy) is risk factor for cardiovascular disease. Guidelines recommend a target plasma t-Hcy level of < 10 umol/l. The aim of the present study was to asses frequancy of HHcy in epileptic patients and to investigate the effect of AEDs on plasma tHcy levels. Method: We surveyed a total of 57 epileptic patients (age range 19 81 years, mean age 44.8 +- 14.5 years). On AEDs mononotherapy was 17 (29.8%) patients and on polytherapy 40 (70.2%), with no other known cause of HHcy. The median duration of therapy was 16 years. Plasma tHcy, folic acid (FA) and vitamin B12 were determined in all patients.
p666 COMPARATIVE EFFICACY OF COMBINATION DRUG THERAPY IN REFRACTORY EPILEPSY N. P. Poolos*, L. N. Warner*, S. Z. Humphreys, and S. Williams *University of Washington, Seattle, WA, USA; Fircrest RHC, Shoreline, WA, USA; and Rainier RHC, Buckley, WA, USA
194 Abstracts
Purpose: We sought to determine whether any AED, in monotherapy or in combination, produced superior efficacy in medically refractory epilepsy by retrospectively analyzing an extensive database of AED therapy of severely developmentally disabled adults with epilepsy. Method: We obtained records charting monthly seizure frequency and AED treatment for 168 patients and analyzed 140 5.8 (mean SEM) months of data for each patient, calculating the average seizure frequency during each unique AED regimen consisting of 1, 2, or 3 drugs in combination from a list of 8 consisting of (in order of frequency of exposure using standard acronyms): LTG, VPA, CBZ, PHT, TPM, LEV, GBP, and ZNS. We then made withinpatient comparisons of the ratio of seizure frequencies with different regimens. Result: For patients on duotherapy, average seizure frequency was 0.81 that of monotherapy, a 19% decrease. However seizure frequency with three drugs at a time was 1.07 that on duotherapy, demonstrating no additional benefit. In comparison of individual AED regimens against a aggregate average of all other regimens, only the combination of LTG/VPA showed superior efficacy (seizure frequency 0.52 of the average) out of 32 regimens. In head-to-head comparisons, LTG/VPA was superior to six other regimens, constituting the majority of 10 statistically significant comparisons. Conclusion: These results suggest that LTG/VPA uniquely shows superior efficacy in medically refractory epilepsy. These results may suggest future prospective trials to confirm the superiority of LTG/VPA, and to better understand the underlying mechanisms of its action.
p668 COST OF ANTIEPILEPTIC DRUG MONOTHERAPIES AND COMBINATION THERAPIES AT A TERTIARY REFERRAL HOSPITAL IN SINGAPORE S. Lim*, S. See, P. Wong, and S. Lim *Nanyang Technological University, Singapore, Singapore; National Neuroscience Institute & Singapore General Hospital, Singapore, Singapore; and Singapore General Hospital, Singapore, Singapore
Purpose: Antiepileptic drug (AED) cost contributes significantly to economic burden of patients and society. We investigate how costly are (1) Newer AEDs (NAEDs) compared to Conventional AEDs (CAEDs) and (2) combination therapies compared to monotherapies at a tertiary referral hospital in Singapore. Method: AED prescription patterns of 682 patients seen by a neurologist from January 2008 to December 2011 were used to calculate AED cost. CAEDs have been available in Singapore for >20 years (Carbamazepine, Phenytoin, Valproate, Phenobarbitone, Clonazepam, Clobazem and Primidone) whereas NAEDs are available for <20 years (Lamotrigine, Gabapentin, Topiramate, Levetiracetam and Pregabaline). They were prescribed mainly based on patients seizure type(s), AED sideeffect profile and/or potential for drug-interaction. Dosages were optimised based on seizure control and tolerability. Total AED cost per year to the patients is calculated according to number, type and dosages of AED(s) in their last prescription. Result: 354 (51.9%) patients were on monotherapies (CAEDs: 253; NAEDs: 101) and 328 (48.1%) were on combination therapies (CAEDs only: 118; CAEDs plus NAEDs: 194; NAEDs only: 16). Cost of CAED monotherapies is 20797 EUR/year (median: 126 EUR/year) and NAED monotherapies is 2293083 EUR/year (1088 EUR/year). Cost of combination therapies with CAEDs only is 1231208 EUR/year (median: 511 EUR), CAEDs plus NAEDs is 3908271 EUR/year (1992 EUR) and NAEDs only is 12748410 EUR/year (3426 EUR). Conclusion: NAEDs are substantially more costly than CAEDs. Their inclusion in combination therapies further increases the economic burden of epilepsy care. These might lead to unsustainable long-term NAED usage and sub-optimal seizure control.
p667 LACOSAMIDE IN ADD ON THERAPY TO TREAT PARTIAL EPILEPSIES O. Daniele*, L. Zummo*, L. Urso, B. Fierro*, and E. Natal* *Palermo, Italy; and Department of Experimental Biomedicine and Clinic Neurosciences University of Palermo, Palermo, Italy
Purpose: Lacosamide is a new molecule which has a marked anticonvulsant activity in partial epilepsy with or without secondary generalization. Aim of the present study is to evaluate tolerability, pharmacokinetics, pharmacodynamics and efficacy of lacosamide when used in association with old and new AEDs. Method: About 30 patients referred to our Center for Diagnosis and Treatment of Epilepsy of the University of Palermo were enrolled suffering from partial epilepsy on bi-polypharmacy. Mean age was 36.6 years, mean age at onset was 15,9 25 patients had intractable epilepsy and 73.3% showed reduction of seizures after 6 months of therapy since addition of lacosamide (doses from 200 to 400 mg/die). Result: Our data show a statistically significant association between age at onset of seizures and drug resistance (p < 0.0038) but not between this latter and mean duration of the disease, as well as between reduction of the frequency of seizures and age at onset or between the type of bi-polytherapy. Conclusion: Our data indicate that, so far, there is not possible to establish the pharmacodynamic and pharmacokinetic mechanism explaining the significant reduction of seizures in patients with lacosamide on addon. Data of the literature suggest that synergism and antagonism are related to various factors such as number of administered drugs, relative mechanism of action, posology, titration which therapeutic results depend on. Facility of administration, tolerability and therapeutical efficacy of lacosamide make it an interesting drug in the treatment of focal pharmacoresistant epilepsies even if further studies are needed to evaluate its interactions with other AEDs.
p669 ANALYSIS OF SEIZURE FREQUENCY REDUCTION BY CONCOMITANT ANTIEPILEPTIC DRUG (AED) USE WITH ADJUNCTIVE PERAMPANEL: POOLED PHASE III RESULTS E. Trinka*, H. Straub, D. Squillacote, H. Yang, D. Kumar, and A. Laurenza *Paracelsus Medical University, Salzburg, Austria; Epilepsieklinik Tabor, Bernau, Germany; and Eisai Neuroscience Product Creation Unit, Woodcliff Lake, NJ, USA
Purpose: To examine seizure frequency reduction with the 5 most frequent concomitant AEDs in the pooled perampanel epilepsy phase III trials (304/305/306). Method: Patients 12 years experiencing treatment-resistant partialonset seizures despite 13 concomitant AEDs were randomized to once-daily, double-blind placebo or perampanel (2, 4, 8 or 12 mg). Analysis of the median percent reduction from Baseline in seizure frequency/28 days by last dose in patients who completed the Maintenance Period (actual dose analysis) was performed for patients concomitantly receiving any one of the 5 most commonly-used
195 Abstracts
AEDs (carbamazepine [n=428], valproate [n=419], lamotrigine [n=397], levetiracetam [n=370], and oxcarbazepine [n=233]) as part of their regimen. Result: Median changes from Baseline in seizure frequency for the 5 most common concomitant AEDs are provided for placebo, 4, 8, 12 mg, respectively (all dose results to be included in poster). Carbamazepine: 13% (n=128), -24% (n=49), -30% (n=116), -18% (n=65). Valproate: 18% (n=128), -28% (n=69), -31% (n=94), -26% (n=31). Lamotrigine: 13% (n=112), -25% (n=64), -33% (n=113), -37% (n=36). Levetiracetam: -18% (n=116), -19% (n=46), -31% (n=92), -39% (n=46). Oxcarbazepine: -5% (n=80), -36% (n=24), -32% (n=54), -38% (n=21). 50% responder rates for each of the 5 AEDs were generally consistent with the median percent changes and will be presented in the poster. Conclusion: Pooled analysis for the 5 most commonly-used concomitant AEDs was performed by actual doses in patients taking 13 AEDs in the phase III perampanel trials. Patients generally received increased benefit from increased doses of perampanel, as previously demonstrated in PK/PD analyses. Support: Eisai Inc.
p671 STEADY-STATE PLASMA AND CEREBROSPINAL FLUID PHARMACOKINETICS OF ESLICARBAZEPINE ACETATE AND OXCARBAZEPINE IN HEALTHY VOLUNTEERS T. Nunes*, J. F. Rocha*, A. Falco, L. Almeida, and P. SoaresDa-Silva *BIAL Portela & Ca. SA, So Mamede do Coronado, Portugal; Health Consulting, Cantanhede, Portugal; University of Aveiro, Aveiro; and University of Porto, Porto, Portugal
Purpose: To evaluate the pharmacokinetics of once-daily eslicarbazepine acetate (ESL) and twice-daily oxcarbazepine (OXC) and their metabolites in cerebrospinal fluid (CSF) and plasma following repeated oral administration. Method: Single-center, open-label, randomised, parallel-group study in healthy volunteers. Volunteers in ESL group (n=7) received 600 mg on Days 13 and 1200 mg on Days 49, once-daily. Volunteers on OXC group (n=7) received 300 mg on Days 13 and 600 mg on Days 49, twice-daily. Plasma and CSF sampling was performed following last dose. Result: Eslicarbazepine was the major drug entity in plasma and CSF, accounting for, respectively, 93.84% and 91.96% of total exposure in the ESL group and 78.06% and 76.42% in the OXC group. The extent of exposure to drug entities R-licarbazepine and oxcarbazepine was approximately 4-fold higher with OXC as compared with ESL. There was relatively little fluctuation from peak to trough (ratio) in the CSF for both eslicarbazepine (1.5 and 1.2 following ESL and OXC, respectively) and R-licarbazepine (1.2 following either ESL or OXC). In contrast oxcarbazepine showed larger differences between peak and trough (3.1 and 6.4 following ESL and OXC, respectively). A total of 45 and 18 treatment-emergent adverse events (TEAEs) were reported with OXC and ESL, respectively. Conclusion: In comparison to OXC, administration of ESL resulted in more eslicarbazepine, less R-licarbazepine and less oxcarbazepine in plasma and CSF, which may correlate with the tolerability profile reported with ESL. The apparent smaller peak-trough fluctuation of eslicarbazepine in CSF than in plasma support once-daily dosing of ESL.

p670 EVENT-RELATED POTENTIALS IN PATIENTS WITH EPILEPSY TREATED WITH LEVETIRACETAM W. J. Derkowski la Zawodowa, Kluczbork, stwowa Medyczna Wyz Pan _ sza Szko Poland
Purpose: The aim of this study was to assess the impact of levetiracetam dose on event-related potentials (ERP) in patients with epilepsy. ERPs are evoked potentials which are obtained by computeraveraging of the electroencephalographic activity in response to stimuli involving cognitive processes of the brain (Duncan C et al. Clinical Neurophysiology 2009; 120:18831908). Levetiracetam is an important new generation antiepileptic drug, especially effective in epilepsy with partial seizures and secondarily generalized partial seizures. Method: The research material consisted of ERP studies performed in 20 patients before and after increasing the dose of levetiracetam during routine treatment of epilepsy. In this study, the ERPs had been generated in response to visual stimuli presented by a proprietary protocol including appearing alternately with two different frequency geometric patterns. Patients had performed the ERP study at least twice: during a routine levetiracetam therapy of epilepsy and after at least two times increase in dose, due to insufficient effect of treatment history. All patients were also performed imaging studies (CT or MRI) of the brain and EEG repeatedly, which in addition to the routine analysis were subjected to computer linear analysis (Derkowski W, Ke dzia A. Computer analysis of EEG activity in patients with epilepsy treated with levetiracetam in The Computer-Aided Scientifical Research , Wroclaw Scientific Society, 2008,233238). Result: The results obtained evidence of a dose effect of levetiracetam on latency, morphology and amplitude of P300 wave. The paper discusses the importance of the results for the assessment of cognitive function in patients during therapy. Conclusion: ERPs allow us to monitor the efficiency of cognitive processes in patients with epilepsy. They are an objective test, based on an analysis of electrical brain activity and subjective effects of the patient for the results are very limited.
p672 EVALUATION OF THE TOLERABILITY OF ADJUNCTIVE RETIGABINE/EZOGABINE DURING THE RECOMMENDED TITRATION SCHEDULE IN ADULTS WITH PARTIAL-ONSET SEIZURES N. Brickel*, S. Derossett, S. Mcdonald, T. Cyr, V. Nohria, and B. Adams *GlaxoSmithKline, Uxbridge, UK; GlaxoSmithKline, Research Triangle Park, NC, USA; and Valeant Pharmaceuticals North America, Durham, NC, USA
Purpose: Retigabine/ezogabine 6001200mg/day is effective as adjunctive therapy in adults with partial-onset seizures. Placebo-controlled trials utilized a titration schedule starting at 300mg/day (TID), with 150mg/ day weekly increases to reach the lowest recommended effective dose of 600mg/day after 2 weeks. Tolerability of this recommended starting dose/titration schedule of retigabine/ezogabine versus placebo is evaluated. Method: Data from placebo-controlled Studies 205, 301 (NCT00232596), and 302 (NCT00235755) were integrated to evaluate
196 Abstracts
each titration step for overall incidence of adverse events (AEs), serious AEs (SAEs), AEs leading to withdrawal, and the most common AEs reported in the trials. Result: Subjects included at each placebo titration step were 300mg/ day=427, 450mg/day=418, and 600mg/day=411, and for retigabine/ezogabine 300mg/day=813, 450mg/day=793, and 600mg/day=774. Incidences were numerically higher for retigabine/ezogabine versus placebo, respectively, for AEs (300mg/day=33% versus 26%; 450mg/ day=25% versus 19%; 600mg/day=27% versus 17%) and AEs leading to withdrawal (300mg/day=5% versus 3%; 450mg/day=4% versus <1%; 600mg/day=6% versus 1%). Incidence of SAEs for retigabine/ ezogabine and placebo were similar: 300mg/day=1% versus <1%; 450mg/day=1% versus <1%; 600mg/day=<1% versus <1%. Of the most commonly reported AEs in the placebo-controlled trials, dizziness, somnolence, and fatigue were more frequent with retigabine/ezogabine than placebo at each titration step, but incidences were similar for headache, confusional state, tremor, abnormal coordination, and blurred vision. Conclusion: In this analysis, the recommended starting dose and titration schedule of retigabine/ezogabine 300mg/day (TID) with 150mg/day weekly increments enables adults with partial-onset seizures to reach the 600mg/day effective dose within 2 weeks of initiating adjunctive therapy with acceptable tolerability. Supported by Valeant Pharmaceuticals International and GlaxoSmithKline.
p674 INTENSE PHARMACOVIGILANCE IN PEDRIATIC PATIENTS WITH FOCAL EPILEPSY TREATED WITH CARBAMAZEPINE MONOTHERAPY B. Rodriguez, C. Medina, and J. Lopez Foundation Central League Against Epilepsy, Bogota, Colombia
Purpose: To identify, evaluate, and propose a strategy of solutions for the effectiveness and security problems that pediatric patients show with focal epilepsy diagnosis and treated with carbamazepine monotherapy. Abstract: The clinical effects of carbamazepine as monotherapy in patients with focal epilepsy would be evaluated through a descriptive observational cross-section study. Materials and Methods: A descriptive observational cross section study. Inclusion criteria: Children with focal epilepsy diagnosis between 5 to 15 years old which have carbamazepine as monotherapy in any commercial presentation and who are outpatients in the LICCE. Exclusion criteria: None. Methodology: Observational descriptive. Result: Supply problems were identified in 77% of patients, among which are: Guardianship (62%), problems with a prescription (55%) claim no sickness medications (50%). Use problems as lack of adherence (61.3%), forgetfulness or difficulty in complying with times, events that interfere with taking the dose. 49.7% in administration consume medications properly. 9% of stores or transports an inappropriate medications. Drug problems (PK / PD) in 89%, as interactions and refractory to treatment. As biopharmaceutical aspects related to the change of trade name of the drug. Conclusions: Pharmacotherapeutic monitoring to identify, prevent and resolve problems that may occur throughout the drug chain and propose individual solution strategies.
p673 SPIRONUCLEUS LINKED GABA DERIVATIVES AS POTENTIAL ANTIEPILEPTIC AGENTS ACTING THROUGH GABA MEDIATION AND INHIBITING NITRIC OXIDE AND FREE RADICALS Y. Perumal, S. Dharmarajan, and S. K. Reddy Birla Institute of Technology & Science-Pilani, Hyderabad campus, Hyderabad, India
Purpose: As spiro nucleus serve as privilege compound, we investigated the hybridization of this nucleus with GABA nucleus to improve the blood brain penetration and bio-activity as anti-epileptics. Method: The synthesized compounds were evaluation in a battery of anticonvusant animal models that include maximal electroshock seizure and subcutaneous chemical-induced models of picrotoxin, pentylenetetrazole and strychnine models. All the compounds were also tested in neurotoxicity models. The doses employed were 30, 100 and 300 mg/kg. The protocol was approved by the Institutional Animal Ethical Committee. Mechanistic studies were also performed to confirm the potential of GABA derivatives on GABA-A receptor using electrophysiology and other mediators studied were those of the levels of nitric oxide and free radicals using spectrophotometer. Result: The synthesized compounds exhibited potential anticonvulsant property in more than 2 animal models of seizure with less or no neurotoxicity compared to standard drugs like phenytoin and carbamazepine. Compounds SH-3, 8 10 and 14 showed potency in lower doses of 10 and 30 mg/kg with no neurotoxicity at the highest dose tested (300 mg/kg). In the mechanistic studies, two representative compounds were evaluated for GABAergic mediation using contraction per se and in the presence of GABA antagonist bicuculline. The EC50 of the most active compound (SH-8) tested was 0.38 micromolar. the concentration of nitric oxide in brain was significantly reduced with compounds SH-8 and 14 and the antioxidant activity was also encouraging. Conclusion: Based on the project results, it can be concluded that Nspiro linked GABA emerges as multifunctional derivatives effective for the treatment of various forms of epilepsy.
p675 TOLERABILITY, SAFETY, AND SIDE-EFFECTS OF LEVETIRACETAM VERSUS PHENYTOIN IN INTRAVENOUS AND TOTAL PROPHYLACTIC REGIMEN AMONGST CRANIOTOMY PATIENTS: A PROSPECTIVE RANDOMISED STUDY K. L. Fuller, Y. Y. Wang, M. Cook, M. A. Murphy, and W. J. DSouza St Vincent's Hospital, Melbourne, Vic., Australia
Purpose: Practical choice in parenteral antiepileptic drugs (AEDs) remains limited despite formulation of newer intravenous (IV) agents and requirements of special patient groups. We compared tolerability, safety, and side-effect profiles of levetiracetam (LEV) against phenytoin (PHT) when given intravenously and in total regimen for seizure prophylaxis in a neurosurgical setting. Method: This prospective, randomised, single-centre study with appropriate blinding comprised evaluation pertaining to IV use three days following craniotomy and at discharge, and to total IV-plus-oral regimen at 90 days. Endpoints were discontinuation because of side-effect, first side-effect, and major side-effect or seizure. Seizure occurrence and sideeffect profiles were also compared. Result: Of 81 patients randomised, 74 (36 LEV, 38 PHT) received parenteral AED. No significant difference attributable to IV use was found between LEV and PHT in discontinuation because of side-effect (LEV 1/ 36, PHT 2/38, p=1.00) or number of patients with side-effect (LEV 1/36, PHT 4/38, p= 0.36). No significant difference was found between LEV and PHT total IV-plus-oral regimen in discontinuation because of sideeffect (hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.21 to 2.92,
197 Abstracts
p=0.72) or number of patients with side-effect (HR 1.51, 95% CI 0.77 to 2.98, p=0.22). More patients assigned PHT suffered an undesirable outcome for safety of major side-effect or seizure (HR 0.09, 95% CI 0.01 to 0.70, p=0.002). Seizures occurred only amongst patients assigned PHT (n=6, p=0.01). Conclusion: LEV and PHT were well-tolerated perioperatively parenterally, and in total prophylactic regimen. Comparative safety and differing side-effect profile of IV LEV supports use as an alternative to IV PHT. Method: 29 consecutive patients were followed. Exclusion criteria: progressive disease, psychogenic seizures, participation in another treatment study, epilepsy surgery or VNS implantation during retigabine treatment. Demographic data, aetiology of epilepsy, treatment response, co-medication and side effects were recorded. Result: 29 patients (19 men, median age 36 (2272)) were included. Median seizure rate before retigabine treatment: 20/month (280), median number of antiepileptic drugs over lifetime: 12 (423), median duration of epilepsy: 27 years (1065). Titration: according to product information, initially up to 600mg/day. Median dosage: 600mg/day (200mg1200mg). Main aetiologies: 44.8% cryptogenic, 13.9% FCD, 10.5% complex cerebral malformation. Unsuccessful epilepsy surgery or VNS-implantation in 34.5% before retigabine treatment. Main co-medications: 41.1% oxcarbazepine, 37.9% levetiracetam, 34.5% lacosamide. Median number off AEDs in co-medication: 2 (14). Responder rates: 0% seizure-free, 6.8% seizure reduction (SR) 7599%, 10.5% SR 50 74% (=17.3% responder), 79.3% SR below 50%, 3.4% worsening. Side effects: Seen in 44.8% of the patients. Main adverse reactions: 20.6% dizziness, 20.6% tiredness, 10.3% diplopia. Medication was tapered in 65.9% of the patients (31.1% lack of effect, 17.2% side effects, 17.2% lack of effect and side effects). Conclusion: Compared to the pivotal trials responder rates in our patients were lower: 17.3% versus 2856% (depending on dosage). This may be due to our highly therapy-resistant population. Main side effects and tapering rate of retigabine due to side effects in our patients were similar to those described in the other trials.
p676 THE EFFECTS OF ESLICARBAZEPINE, R-LICARBAZEPINE, OXCARBAZEPINE AND CARBAMAZEPINE ON SODIUM CURRENTS THROUGH NAV1.3 CHANNELS L. Wright*, K. Brady, S. Hebeisen, and P. Soares-Da-Silva *BIAL Portela & Ca. SA, So Mamede do Coronado, Portugal; BSYS GmbH, Witterswil, Switzerland; and University of Porto, Porto, Portugal
Purpose: Eslicarbazepine acetate (ESL) is approved in Europe as adjunctive therapy for partial-onset seizures in adults. ESL undergoes rapid and extensive first pass metabolism via hydrolysis to eslicarbazepine, its major active metabolite. This study was aimed to determine the effects of eslicarbazepine, R-licarbazepine (minor metabolite of ESL), oxcarbazepine (OXC) and carbamazepine (CBZ) on the human NaV1.3 sodium channel expressed in CHO cells. Method: About 2448 hours following transfection with human NaV1.3 cDNA, cells were ready for electrophysiological experiments. The whole-cell patch-clamp technique was used to investigate the effects of eslicarbazepine, R-licarbazepine, OXC and CBZ on NaV1.3 inward peak currents. These compounds were tested at various holding potentials (-80 mV and -60 mV). The affinities of the test compounds (250 lM) for the resting (KR) and inactivated (KI) states were examined after 15 s conditioning pre-pulses ranging from -120 mV to -40 mV. Result: The potency of inhibition was highly sensitive to the holding potential, increasing with depolarisation, but the affinity of eslicarbazepine was approximately 3-fold lower than CBZ and OXC in more depolarized conditions. All compounds demonstrated a much higher affinity for the inactivated (KI) state of the channel, but the affinity of eslicarbazepine and R-licarbazepine for VGSCs in the resting (KR) state was about 2-fold lower than that of CBZ and OXC. Conclusion: Eslicarbazepine demonstrated a greater selectivity for the inactive state of NaV1.3 sodium channels, which is the common feature of the rapidly firing neurons, over their resting state as compared to CBZ and OXC.
p678 THE EFFECTS OF MORPHINE AND NALOXON ON SPONTANEUSE SEIZURE ACTIVITY IN HIPPOCAMOPAL SLICES A. Alijarahi, and M. Amini Qazvin, Iran
Purpose: There is however very little information available about the effects of morphine on recurrent spontaneous seizures. Objective: Therefore the present study was designed to determine the effects of different dose of morphine and Naloxon on spontaneous seizure activity in epileptogenic hippocampal slices. Method: Hippocampal slices (~400 lm) were prepared from young Wistar rats (P15- 25). Seizure activity was induced by continuously perfusing the slices with low Mg2+ perfusate in an interface recording chamber. Extracellular recordings were performed in the hippocampal CA1 pyramidal cell layer. Low Mg2+ caused spontaneous epileptic activity in all studied hippocampal slices. Seizure activity was quantified by measuring the amplitude and duration of the ictal events as well as their number before and after the application of the study drugs. Also, the numbers of interictal spikes were determined to complement the analysis of seizure discharges before and after drug application. Result: Findings: Low doses of morphine (10 lM) suppressed seizure activity, whereas high doses of morphine (15, 30 & 100 lM) potentiated seizure activity in a dose dependent manner. This effect was completely reversed by the addition of Naloxon (10 M). Differential effects of morphine on seizures, suggests that morphine in different concentrations acts on different receptor subtypes or by different mechanisms. Activation of opioid receptors by morphine lead to suppression of GABAergic synaptic transmission thereby disinhibiting pyramidal neurons, resulting in the enhancement seizures. Conclusion: Activation of opioid receptors by morphine lead to suppression of GABAergic synaptic transmission thereby disinhibiting pyramidal neurons, resulting in the enhancement seizures.
p677 FIRST EXPERIENCE WITH RETIGABINE IN A HIGHLY DRUG RESISTANT POPULATION OF 29 EPILEPTIC PATIENTS C. Kurth, and B. J. Steinhoff Epilepsy Centre Kork, Kork, Germany
Purpose: Retigabine is available in Germany since May 2011. This study reflects the practical experiences in a tertiary referral EpilepsyCentre.
198 Abstracts
Neuroimaging and Neurophysiology 7 Wednesday, 03 October 2012

p679 THE UTILITY OF HIGH FREQUENCY OSCILLATIONS ON MEG AND INTRACRANIAL EEG IN LOCALISING SEIZURE FOCI IN PATIENTS WITH REFRACTORY EPILEPSY UNDERGOING PRESURGICAL EVALUATION A. Lemesiou*, M. C. Walker*, R. Rodionov*, B. Diehl, and F. Rugg-Gunn* *UCL Institute of Neurology, London, UK; and National Hospital for Neurology and Neurosurgery, London, UK
Purpose: With 30% of epilepsy patients not having spikes on MEG, alternative markers of epileptogenicity are sought. High frequency oscillations (HFOs) have been documented in patients with simultaneous MEG and intracranial EEG (iEEG) recordings and co-localisation confirmed. We compared the ability of iEEG and MEG to identify alternative markers of epileptogenicity in surgical candidates. Method: This was a retrospective analysis of MEG and iEEG data from 15 pre-surgical patients. A ten minute period of slow-wave sleep was selected for iEEG analysis. This was processed for visual detection of HFOs which were also confirmed using newly-developed EEG algorithms and marked on topographic maps. Additionally, ten minutes of continuous interictal resting state MEG were reviewed with a high pass filter set at 40Hz. The presence of any high frequency activity was visually identified and localised using the patient's own segmented cortex as source space; source analysis using s-LORETA current density reconstruction (CURRY-5). Result: Analysis of the 15 patients revealed only 1 without interictal MEG spikes. Analysis of HFOs in this patient revealed that channels with the greatest number of HFOs on iEEG were found to co-localise with the seizure onset zone in the left frontal region. Despite absence of standard interictal epileptiform discharges on MEG, we identified high frequency oscillatory activity around 120Hz which localised to the left frontotemporal region, consistent with other localising data. Conclusion: The identification of high frequency oscillatory activity in MEG may be a marker of epileptogenicity contributing to non-invasive lobar localisation in patients without traditional interictal epileptiform discharges on MEG.
cal pathways and functional connectivity of the thalamus with cortical networks. Result: Our findings demonstrated bilateral atrophy in the dorsal anterior and ventral posterior thalamus in the JME group. Analysis of diffusion tractography-derived structural connectivity showed a reduction in connectivity from the anterior thalamus to the supplementary motor area (SMA) and preSMA. The degree of structural connectivity was positively correlated with the duration of epilepsy. Finally, reduced thalamic functional connectivity (defined using fMRI) was detected between the same anterior thalamic region and a cortical mesial frontal resting state network. The significance of all findings are corrected for multiple comparisons (p<0.05). Conclusion: These multi-modal and complementary results suggest dysfunction of the anterior thalamo-cortical network in JME, in keeping with the thalamo-cortical hypothesis of IGE and frontal abnormalities implicated in JME.
p681 THE LOCATION OF FAST RIPPLES IS STATIONARY AS FOCAL SEIZURES EVOLVE T. Nowacki, D. Gross, B. Wheatley, S. N. Ahmed, and J. Jirsch University of Alberta, Edmonton, AB, Canada
Purpose: High Frequency Oscillations (80600Hz) can be recorded from intracranial EEG (iEEG). Discrete, localized 250600Hz Fast Ripples (FRs) have mainly been studied in the interictal iEEG and may reflect epileptogenic tissue. We investigate the spatial distribution of FRs during the evolution of epileptic seizures with respect to the conventionally-defined seizure-onset zone (SOZ). Method: Eighteen focal seizures from six consecutive patients undergoing iEEG sampled at 2000 Hz were selected. Channels were classified on conventional review of seizures as SOZ, secondary propagation, or uninvolved. Sampled 10 second sections from pre-ictal, ictal onset and propagation periods were visually analyzed using filters and with increased gain for the presence of FRs. Result: 1,955 FR events were identified. FRs increased in number with seizure evolution (median counts: 19, 55, 96.5 at the three time periods, p=0.023, Kruskal-Wallis test). During the pre-ictal period there was no significant difference in FR activity between groups (1-way ANOVA, p=0.359). At ictal onset, mean FR activity in the SOZ channels was significantly greater than both non-SOZ groups (1-way ANOVA, p=0.010), and the difference increased at full propagation (1-way ANOVA, p 0.001). Channels containing the greatest number of FRs (2 SD mean) lay within the SOZ in 5/6 patients. Conclusion: FRs predominate during electrographic seizure activity as compared to the inter-ictal time period. They most often remain confined to a few channels in close proximity within the conventionally-defined seizure-onset zone during the evolution of seizures. We speculate that the locations of FRs in focal seizures may specify epileptogenic areas more precisely than conventional review.
p680 STRUCTURAL AND FUNCTIONAL CHANGES IN THALAMO-CORTICAL CONNECTIVITY REFLECT A SPECIFIC IMPAIRED NETWORK IN JUVENILE MYOCLONIC EPILEPSY J. OMuircheartaigh*, C. Vollmar, G. J. Barker, V. Kumari, M. Symms, P. J. Thompson, J. Duncan, M. Koepp, and M. P. Richardson *Brown University, Providence, RI, USA; University of Munich, Munich, Germany; King's College London, London, UK; and UCL, London, UK
Purpose: Juvenile Myoclonic Epilepsy (JME) is the most common subtype of idiopathic generalised epilepsy (IGE) with a presumed thalamocortical basis in seizure pathology. Here we investigate alterations in thalamic structure and thalamo-cortical connectivity in Juvenile Myoclonic Epilepsy (JME) using multimodal magnetic resonance imaging (MRI). Method: A cohort of patients with JME (28, mean age 33.6yrs) and healthy control participants (38, mean age 31.8yrs) underwent a series of structural, diffusion and resting-state functional MRI scans. Investigations focused on thalamic shape, structural connectivity of thalamocortiEpilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x
p682 INFERRING PATIENT-SPECIFIC PHYSIOLOGICAL PARAMETERS FROM INTRACRANIAL EEG: APPLICATION TO CLINICAL DATA S. Shmuely*, D. R. Freestone, D. B. Grayden*, D. Nesic*, and M. Cook* *NeuroEngineering Laboratory, Melbourne, Vic., Australia; and St. Vincent's Hospital, Melbourne, Vic., Australia
Purpose: Intracranial EEG (iEEG) provides information regarding where and when seizures occur, whilst the underlying mechanisms are hidden. However physiologically plausible mechanisms for seizure gen-
199 Abstracts
eration and termination are explained by neural mass models, which describe the macroscopic neural dynamics. Fusion of models with patient-specific data allows estimation and tracking of the normally hidden physiological parameters. By monitoring changes in physiology, a new understanding of seizures can be achieved. This work addresses model-data fusion for iEEG for application in a clinical setting. Method: Data was recorded from three patients undergoing evaluation for epilepsy-related surgery at St. Vincent's Hospital, Melbourne. Using this data, we created patient-specific neural mass mathematical models based on the formulation of Jansen and Rit (1995). The parameters that were estimated include the synaptic gains, time constants, and the firing threshold. The estimation algorithm utilized the Unscented Kalman Filter (Julier and Uhlmann, 1997). Result: We demonstrate how parameters changed in relation to seizure initiation, evolution and termination. We also show within-patient (across different seizures) and between-patient specificity of the parameter estimates. Conclusion: The fusion of clinical data and mathematical models can be used to infer valuable information about the underlying mechanisms of epileptic seizure generation. This information could be used to develop novel therapeutic strategies Purpose: Progressive myoclonic epilepsy (PME) is a heterogeneous syndrome of rare disorders presenting with similar clinical features. This study was designed to investigate if there was, 1) any correlation between the electrophysiological findings and the clinical course of this syndrome, 2) any change in the excitability of brainstem pathways besides the well-known cortical hyperexcitability. Method: Sixteen PME patients, whose clinical and genetic features will be presented separately, were included. Control groups consisted of 15 healthy controls (HC) and 7 patients taking multiple antiepileptic drugs (patient controls=PC). Median somatosensory evoked potentials (SEP), C reflexes from thenar eminences and blink reflexes (BR) to supraorbital stimulation were studied. Result: Cortical N20 potential latencies were delayed and N20-P25, P25-N35 amplitudes were increased in PME group (p<0.05). Giant SEPs were recorded bilaterally in 8 PME cases whose disease duration was found to be longer than the other patients (p=0.045). C reflex was recorded in 9 cases, 6 of whom also had giant SEPs. Higher stimulus intensities were required in PME group for eliciting the BRs. The latencies of ipsilateral R2 responses (iR2) were prolonged in PC and PME groups, which were more pronounced in the former (p<0.05). The amplitude, duration and areas of iR2s were generally decreased in PC and increased in PME group (p<0.05). Conclusion: The electrophysiological markers of cortical hyperexcitability, giant SEPs and C reflexes, may have a relation with the course and duration of the disease. BR findings obtained in this study imply the presence of an increased excitability at the brainstem level.
p683 THE EVENT RELATED POTENTIAL P300 AND REACTION TIME IN EPILEPSY V. P. Ivetic*, M. F. Knezevic-Pogancev, and N. Naumovic* *Medical Faculty, Novi Sad, Serbia; and Institute for child and youth health care of Vojvodina, Novi Sad, Serbia
Purpose: The research goal was the determination of amplitude and latency value of the event related potential P300 and the determination of the simple reaction time, in right-handed female persons with idiopathic generalized epilepsy and in healthy volunteers. Method: 50 female persons aged 19 to 23 years participated in the study. 30 patients with idiopathic generalized epilepsy (first group) were compared with 20 healthy persons (control). The reserch workers were using the "oddball paradigm with two tones: standard (90dB, 1000Hz) and "expected-target (90dB, 2000Hz) for the registration of the P300 potential above Fz and Cz (10/20 system). The subjects got instructions to press a button, as fast as they can, whenever they hear the expected tone. Result: The average latency values of P300 event related potential were 342.2ms11.41 above Fz and 352.1ms5.79 above Cz area in the first group; and 313.97.3ms above Fz; 319.1ms12.5 above Cz in the control. The amplitudes were 11.8lV6.74 above Fz and 13.7lV1.24 above Cz in the first group; and 12.64lV1.22 above Fz and 14.26lV1.35 above Cz in the control group. P300 latency in first group was significantly longer. Epileptic persons were decreased P300 amplitude but not significantly as compared with healthy persons. There was no relation between P300 latency and amplitude with seizure onset, duration frequency. Significantly faster RT was found in healthy persons. In patients with epilepsy were found a significant positive correlation between RT duration and latency of P300 Conclusion: The epilepsy has impact on late components of P300 potential and reaction time.
p685 NEUROPROTECTIVE POTENTIAL OF STIRIPENTOL AGAINST OXYGEN AND GLUCOSE DEPRIVATION OR GLUTAMATE EXPOSURE IN CULTURED RAT CORTICAL NEURONS V. Riban*, M. Verleye*, N. Callizot, and R. Steinschneider *BIOCODEX, Compiegne, France; and Neuron Expert, Marseille, France
Purpose: Experimental and clinical data indicate that epilepsy and seizures lead to neuronal cell loss and irreversible brain damage underlying behavioural and cognitive problems particurlarly in Children. Stiripentol (Diacomit(c)) is an antiepileptic compound prescribed in chilhood epilepsies such as Dravet syndrome. We examined the potential neuroprotective activity of stiripentol in two in vitro models mimicking neuronal death: neuronal cultures from mature rat cerebral cortex exposed to anoxia and glucose deprivation or glutamate injury. Method: Anoxia (95%N2/5% CO2) for 2 hours followed by-re-oxygenation for 24 hours and glutamate (40lM for 20min) induced neuronal toxicity. Quantification of neuronal death was based on the immunolabeling intensity of cytoskeleton components: the 68/200 KDa neurofilament subunits. Result: Stiripentol up to 100lM was devoid of any effects on the neurofilaments immunolabeling density in normoxic and control conditions. Anoxia and glutamate induced a decrease in neuronal labelling of 60 and 40% respectively. At therapeutically relevant concentrations (30 and 100lM), stiripentol reversed the anoxia-induced-effects in neuronal labelling in the case of pre-treatment but was ineffective when post-treated. Stiripentol at 100lM included in the culture medium before or after glutamate exposure significantly increased the amount of surviving neurons compared to controls. Conclusion: Stiripentol exhibited neuroprotective properties. Several hypotheses, such as interactions between stiripentol and the glutamatergic system and/or with membrane calcium channels can be suggested to explain these effects.
p684 ELECTROPHYSIOLOGICAL FEATURES IN PROGRESSIVE MYOCLONIC EPILEPSY Z. Matur*, O. E. Ore, N. Bebek*, B. Baykan*, C. Gurses*, A. Gokygt*, and A. E. Oge* *Istanbul Universty Istanbul Medical Faculty, Istanbul, Turkey; and Ozel Memorial Hizmet Hospital, Istanbul, Turkey
200 Abstracts
p686 VISUAL CORTEX HYPEREXCITABILITY IN IDIOPATHIC GENERALIZED EPILEPSIES WITH PHOTOSENSITIVITY: A TMS STUDY F. Brigo*, L. G. Bongiovanni, R. Nardone, A. Fiaschi*, and P. Manganotti *University of Verona, Verona, Italy; Verona, Italy; Franz Tappeiner Hospital, Merano, Italy; and University of Verona, Verona, Italy
Purpose: To investigate the cortical excitability levels in 33 patients with IGEs, and in a subgroup of 8 patients affected by idiopathic generalized epilepsies with photosensitivity, compared with 12 healthy controls. Method: Using transcranial magnetic stimulation we explored the excitability of both the primary motor cortex and the primary visual cortex determining the resting motor threshold (rMT) and the phosphene threshold (PT). Result: An inversion of the PT/rMT ratio (PT/rMT ratio <1) was found in 87.5% epileptic patients with photosensitivity. All patients with active epilepsy and photosensitivity showed this inversion. The differences in the PT/rMT ratio of epilepsy patients with photosensitivity and those of healthy controls (p=0.007) and with epilepsy patients without photosensitivity (p=0.016) were statistically significant. 91.7% of the controls reported phosphenes, compared with 45.5% of patients with idiopathic generalized epilepsy (p=0.015). Phosphenes were reported more frequently among epilepsy patients with photosensitivity (87.5%) than in patients with active epilepsy without photosensitivity (30.8%) (p=0.038) and with patients with epilepsy in remission without photosensitivity (33.3%) (p=0.054). No differences were found between epilepsy patients with photosensitivity and controls (p=0.648). Conclusion: The marked decrease in PT and the high phosphene prevalence in epilepsy patients with photosensitivity indicate a regional hyperexcitability of the primary visual cortex. Results of our study argue therefore against the presence of homogeneously distributed hyperexcitability in idiopathic generalized epilepsies associated with photosensitivity. The inversion of the PT/rMT ratio might represent a useful biomarker of this abnormal response of the human brain to visual stimulation. Result: Our results show the existence of highly localized and stable synchronization areas in both the lateral and the mesial areas of the temporal lobe ipsilateral to the clinical seizures. Synchronization areas seem to play a central role in the capacity of the epileptic network to generate clinical seizures. Resection of stable synchronization areas is associated with elimination of seizures; nonresection of synchronization clusters is associated with the persistence of seizures after surgery. Conclusion: We suggest that synchronization clusters and their stability play a central role in the epileptic network, favoring seizure onset and propagation. We further speculate that the stability distribution of these synchronization areas would differentiate normal from pathologic cases.

p688 HIGHLY FOCAL BOLD ACTIVATION ON FMRI IN PATIENTS WITH PROGRESSIVE MYOCLONIC EPILEPSY AND DIFFUSE GIANT SOMATOSENSORY EVOKED POTENTIALS P. Manganotti*, S. Storti*, E. Formaggio*, F. Brigo*, A. Delfelice*, I. Boscolo Galazzo*, L. Canafoglia, and L. G. Bongiovanni* *Universit degli Studi di Verona, Verona, Italy; and IRCCS Foundation Besta Neurological Institute, Milan, Italy
Purpose: Aim of the study was to analyzed the effect of afferent input on patterns of brain electrical activation in eour patients with progressive myoclonic epilepsy (PME) by measuring the somatosensory evoked potential (SSEP) amplitude at the scalp after median-nerve stimulation and examining the changes in the functional magnetic resonance imaging blood oxygen level-dependent (fMRI BOLD) signal. Method: To locate the right median nerve at the wrist, the stimulation intensity and electrode sites were altered until stimulation produced an observable thumb twitch. Current stimulation during fMRI recording was done in an alternating sequence of 26 seconds. Coregistration System (Micromed) was used. Result: High amplitude SSEPs diffused over the scalp with high amplitude N20 and P25 were oberved in all the patients, but it was associated with highly focal BOLD activation of the contralateral sensorimotor areas. By contrast, no diffuse activation of either the frontal or the posterior parietal cortical areas was observed, as seen with previously recorded data of SSEPs from a healthy control group. Conclusion: The highly focal BOLD activation in these patients suggests that cortex hyperexcitability might be limited to the sensorimotor cortex in PME. The combined EEG-fMRI findings highlight a dissociation between BOLD activation and neurophysiological findings.
p687 STABILITY OF SYNCHRONIZATION CLUSTERS AND ICTOGENICITY IN TEMPORAL LOBE EPILEPSY G. Ortega*, A. Palmigiano, R. Garca De Sola*, and J. Pastor* *Hospital Universitario de la Princesa, Madrid, Spain; and University of Buenos Aires, Buenos Aires, Argentina
Purpose: Identification of critical areas in presurgical evaluations of patients with temporal lobe epilepsy is the most important step prior to resection. According to the epileptic focus model, localization of seizure onset zones is the main task to be accomplished. Nevertheless, a significant minority of epileptic patients continue to experience seizures after surgery (even when the focus is correctly located), an observation that is difficult to explain under this approach. However, if attention is shifted from a specific cortical location toward the network properties themselves, then the epileptic network model does allow us to explain unsuccessful surgical outcomes. Method: The intraoperative electrocorticography records of 20 patients with temporal lobe epilepsy were analyzed in search of interictal synchronization clusters. Synchronization was analyzed, and the stability of highly synchronized areas was quantified. Surrogate data were constructed and used to statistically validate the results.
p689 INTRACRANIAL EEG-FMRI IN EPILEPSY: A PRELIMINARY APPROACH TO MODELING VERY FREQUENT SPIKE DISCHARGES D. W. Carmichael*, L. Hu, U. Chaudhary, G. Iannetti, S. Vulliemoz, R. Rodionov, R. Thornton, and L. Lemieux *UCL Institute of Child Health, London, UK; Southwest University, Chongqing, China; UCL Institute of Neurology, London, UK; UCL, London, UK; and University Hospital of Geneva, Geneva, Switzerland
201 Abstracts
Purpose: We have recently recorded intracranial electroencephalography (icEEG) in epilepsy patients undergoing presurgical evaluation with simultaneous fMRI observing a strict protocol to ensure minimal risk of patient injury. Many epileptifom interictal discharges (IEDs) are recorded (often<1 per second). When IEDs are very frequent they are poorly modeled by uniform instantaneous events. We investigate if modelling IED amplitude and morphology increased sensitivity to IED related BOLD changes using a new method. Method: Three temporal lobe epilepsy patients undergoing presurgical evaluation with icEEG and were scanned within strict safety criteria. IEDs were visually coded; the most frequent spike type was selected from the most prominent spiking contact. A model containing amplitude, latency and dispersion terms for each IED phase (e.g. spike and wave) was fitted to each of these IED. The resulting coefficients were entered as IED features along with onsets as regressors in a model of fMRI signal changes. The variance explained by IED onsets and features was obtained using an inclusive threshold (p<0.001 uncorrected, >5 adjacent voxels) in each patient. Result: Patient#1: IED onset revealed diffuse responses with a small cluster in the temporal lobe. IED features explained additional variance in one left-mid-posterior temporal cluster. Patient#2: IED onset showed no result. IED features showed a left parietal and right-basal-temporal changes. Interestingly, the dispersion coefficients revealed clusters within the right and left temporal lobes which both lay within the IZ. Patient#3: IED onset showed distributed clusters predominantly contralateral to the IZ. IED features revealed an additional right-mid-posterior temporal cluster ipsilateral to the IZ.
p691 INFERRING PATIENT-SPECIFIC PHYSIOLOGICAL PARAMETERS FROM INTRACRANIAL EEG: THEORETICAL STUDIES D. R. Freestone*, D. B. Grayden*, M. Cook*, and D. Nesic *University of Melbourne, Parkville, Vic., Australia; and NeuroEngineering Laboratory, Melbourne, Vic., Australia
Purpose: Mathematical neural mass models describe the biophysics of the EEG. These models are used in epilepsy research to generate new hypotheses for changes in physiology that lead to generation of seizures. Until now, these models have had limited use in the clinic since they describe general neurodynamics, while pathologies are patient-specific. This work describes theoretical aspects of a method for creating patientspecific neural mass models from intracranial EEG (iEEG). Method: Artificial data were generated using a neural mass mathematical model (Jansen and Rit, 1995) so that the actual parameters were known and estimation accuracy could be evaluated. The dynamics of the model that were estimated were firing rates and membrane voltages. The estimated parameters governed the shape of post-synaptic potentials, connectivity strength between neural populations, and firing thresholds. An augmented state-space model was used with the Unscented Kalman Filter (Julier and Uhlmann, 1995) to solve the estimation problem. Result: Use of the artificial data demonstrated that it is possible to estimate the dynamics and parameters of the model from iEEG. Estimation accuracy and robustness were also demonstrated. Conclusion: The data assimilation framework allows observation of physiological parameters that govern neurodynamics. Patient-specific models have the potential to lead to tailored drugs delivery and facilitate engineering techniques for feedback control of seizures. B.H. Jansen and V.G. Rit. Electroencephalogram and visual evoked potential generation in a mathematical model of coupled cortical columns, Biological Cybernetics (1995), 73(4) 357366 S.J. Julier and J.K. Uhlmann. A new extension of the Kalman filter to nonlinear systems, SPIE 3068 (1997), 182193.
p690 VOLUMES OF SUBCORTICAL STRUCTURES IN IDIOPATHIC GENERALISED EPILEPSY AND UNAFFECTED FAMILY MEMBERS F. A. Chowdhury, G. J. Barker, L. Nashef, R. D. Elwes, and M. P. Richardson King's College Hospital, London, UK
Purpose: Reduced volumes of thalamus and caudate have been reported in patients with idiopathic generalised epilepsy (IGE). It is uncertain whether this is part of the underlying disease process, or a consequence of seizures or drug treatment. Method: Forty normal control subjects, 30 patients with IGE, and 36 unaffected first-degree relatives of the patients were studied. A T1weighted SPGR image was acquired at 3T for each subject, with isotropic voxels of 1.1mm. Each scan was processed using the software package FSL-FIRST (FMRIB, Oxford). Volumes of thalamus, caudate, putamen and pallidum were obtained for left and right hemispheres (8 volumes for each subject). Statistical testing used Bonferroni correction for 8 comparisons. Result: Patients had lower volumes of thalamus, caudate, putamen and globus pallidus bilaterally than relatives, who in turn had lower volumes of these regions than controls. For right thalamus and right caudate these were significant, with patients and relatives showing significantly lower volumes than controls (right thalamus. F=5.51, p=0.005; post hoc patients versus controls p=0.032, relatives versus controls p=0.002; right caudate F=4.95, p=0.006; post hoc patients versus controls p=0.006, relatives versus controls p=0.014). In all other regions, there were strong trends but these were not statistically significant after correcting for multiple comparisons. Conclusion: Volume reduction of subcortical structures is found in unaffected relatives of patients with IGE as well as the patients themselves, suggesting this is not related to the occurrence of seizures or due to treatment.
p692 EFFECTS OF VAGAL NERVE STIMULATION ON VOCAL FUNCTIONS E. Gardella*, P. Schiavo, A. Maccari, E. Zambrelli, C. Marras, G. Felisati, and M. P. Canevini *Filadelfia Epilepsihospitalet, Dianalund, Denmark; St Paolo Hospital, Milan, Italy; and IRCCS Neurological Institute Carlo Besta, Milano, Italy
Purpose: This study aims to describe the subjective and objective effects of Vagal Nerve Stimulation (VNS) on vocal functions Method: We studied 14 patients (7 males/ 7 females) affectred by drug resistant epilepsythat underwent VNS implantation. Mean patients agewas 41 years. Latency from implantation ranged from 1 to 8 years. Patients subjecticve disturbs have been investigated performing an unstructured colloquium and by self administered questioner. Vocal functions have been studied by means of larygeal fibroscopy (LF) and vocal analysis (MultiDimensionalVoiceProgram Kay Pentax TM) both at rest and dring VNS stimulation. Result: (a) immediatly after implantation patients (n4) referred chronic dysphonia +/) dysphagia, that could periodically and intermittently worsen, in relation to VNS discharge. Chronic disturbs gradually recovered 23 months after surgery, whilst in most cases intermittent dysphonia was also present for 310 days after each following increment of the VNS amperage. LF and VA documented unilateral hypomobility of vocal cord and phonological alteration while the stimulator was switched off; disturbs worsened during VNS discharges. (b)
202 Abstracts
patients studied (n10) after 18 years from implantation, occasionally referred vocal disturbs (2 patients presented sporadically intermittent dysphonia). LF and VA documented in 9/10 cases a residual hypomobility of the vocal cord, functionally compensated from the contralateral vocal cord hyperadduction. Conclusion: We documented that both surgergical procedure and electrical stimulation of the vagal nerve can perturb the motility of the vocal cord homolateral t the side of implantation. This incostantly produces negative effects on vocal productions and occasionally is referred by patients as a chronic disturb. Method: A total number of 20 patients with suspicion of epilepsy, between 24 months and 16 years old, have been studied during the year 20112012 with videoEEG monitoring from 24 to 96 hours. Tolerability to the exploration is valued, the required time to register a seizure, the number of the recorded seizures and the efficiency in each patient. Result: Al the patients tolerated the realisation of the exploration. In 19 of the 20 patients of the study the events that the parents referred as seizures were recorded, letting to approach to a definitive diagnosis of the pathology. In 6 of the 20 patients pseudoseizures were diagnosed, letting to proceed to the stop of medication. Conclusion: The utilisation of VEEG in pediatric epilepsy unit is not only useful in obtaining the accurate diagnosis, but also in avoiding the treatment in patients with uncertain symptoms.
p693 LOCALISING AND LATERALISING VALUE OF ICTAL EEG PATTERNS IN MESIAL AND NEOCORTICAL TEMPORAL LOBE EPILEPSY E. T. Lim*, S. Kovac, T. Wehner, C. Scott, and B. Diehl *Instituta of Neurology, London, UK; Department of Clinical and Experimental Epilepsy, London, UK; The National Hospital for Neurology and Neurosurgery, London, UK; and UCL Institute of Neurology, London, UK
Purpose: To study the localizing and lateralizing value of ictal scalp EEG patterns in patients with mesial and neocortical temporal lobe epilepsy (TLE). Method: Eighty-five EEG seizures in 39 patients with TLE were analysed. The first 20 seconds of seizure patterns were classified as rhythmic (alpha, theta, delta), repetitive epileptiform or arrhythmic. Their distribution was classified as regional, lateralized, lateralized-maximum temporal, generalised, generalised- bi-temporal emphasis, or bi-hemispheric independent. The location of the epileptogenic zone was determined by seizure freedom after lesionectomy or temporal lobectomy with histologically confirmed hippocampal sclerosis (n=25) or intracranial EEG recording (n=14). Result: Sixteen patients had neocortical TLE (intracranial EEG recording n=9 and temporal lesionectomy n=7) and 23 mesial TLE (intracranial EEG recording n=5, temporal lesionectomy n=2 and anterior temporal lobectomy n=16). Patients with mesial TLE were more likely to have rhythmic or repetitive epileptiform ictal patterns (54% in mesial TLE versus 23% in neocortical TLE), whereas patients with neocortical TLE were more likely to have arrhythmic ictal patterns (17% neocortical TLE versus 6% mesial TLE) (p=0.04, Fisher's exact test). There was no difference in ictal onset frequencies. In mesial TLE, 58% of seizures localized, 37% lateralized (including temporal maxima) and 5% bi-hemispheric independent. In neocortical TLE, 40% of seizures localized, 33% lateralized and 7% bihemispheric independent. Generalised ictal onset was present in 20% of neocortical TLE, but never seen in mesial TLE (p=0.15, Fisher's exact test). Conclusion: Arrhythmic ictal patterns and possibly a generalised distribution should raise suspicion of neocortical ictal onset in TLE.
p695 EEG FINDINGS AND TREATMENT IN JUVENILE MYOCLONIC AND JUVENILE ABSENCE EPILEPSIES S. V. Kasradze*, G. Japaridze*, D. Kvernadze*, L. Zhizhiashvili*, T. Gagoshidze*, G. Lomidze*, O. Toidze*, and J. W. Sander *Institute of Neurology and Neuropsychology, Tbilisi, Georgia; and UCL Institute of Neurology, London, UK
Purpose: Focal EEG abnormalities are often described in idiopathic generalized epilepsy (IGE), but there have been few investigations with respect to EEG and AED treatment. Aim: To assess EEG features in juvenile myoclonic epilepsy (JME) and juvenile absence epilepsy (JAE) in relation to AED treatment. Method: EEGs of 122 consecutive people, aged 9 to 54 years (mean SD =25.410.3), admitted to the INN between 01/08 and 2/10 and diagnosed with JME (n=95) and JAE (n=27), were analyzed. 41 of them were deemed as treated appropriately, [regular treatment regime and adequate dosage of valproate (n=29), levetiracetam (n=3), lamotrigine (n=2), phenobarbital (n=5) or polytherapy; 21 were deemed as treated inappropriately [mainly carbamazepine mono-therapy] 60 people were drug-nave. Result: EEG was normal in 21/122 (17%). Of those on appropriate treatment it was normal in 32% and this compares to 13% in drugnave subject and in none of those inappropriately treated (p = 0.004). Specific Generalized epileptiform abnormalities were seen in 32% of people with appropriate AED treatment, in 86% with inappropriate treatment and in 73.3% drug-nave individuals. Focal epileptiform abnormalities were noted in 81% of people with inadequate treatment, in 50% of drug-nave (p = 0.013), in 49% of adequately treated people (p = 0.015). Conclusion: In this Georgian sample of people with IGE, appropriate antiepileptic treatment seems more likely to be associated with the presence of normal EEG patterns in people with IGE; inappropriate drugtreatment seems to have no effect on generalized discharges and seems to exarcebate focal epileptiform abnormalities.
p694 VIDEO-ELECTROENCEPHALOGRAM MONITORING IN A PEDIATRIC EPILEPSY UNIT P. Giner-Bayarri, N. Torres, K. Quintero-Hernandez, J. Moliner-Ibaez, M. R. Chilet-Chilet, A. Cnovas, G. ZalvePlaza, R. Bretn, and L. Ruiz-Marquez Hospital Universitario Dr. Peset, Valencia, Spain
Purpose: The characteristics of epilepsy in childhood and the differences that show with adult population, make it increasingly necessary, to create specific units for diagnosis and treatment of epilepsy in pediatric patients. To assess the effectiveness of the videoelectroencephalogram (vEEG) in epileptic children.
p696 TOWARDS GUIDELINES FOR THE RATIONAL USE OF THE PROLONGED EEG F. Z. Javaid, T. Tidswell, and H. Angus-Leppan Royal Free Hospital, London, UK
Purpose: The diagnosis of epilepsy is primarily clinical. Basic EEG investigations are usually requested in order to confirm or aid the
203 Abstracts
diagnosis. When these results are normal or inconclusive, patients are further referred for more specialised investigations. This study aimed to compare and assess the relative uses of prolonged EEGs (ambulatory EEG versus video telemetry) in the diagnosis and clinical management of epilepsy. Method: 104 consecutive patients had a prolonged EEG between November 2009 and February 2011. Clinical records were assessed retrospectively for changes in either diagnosis or clinical management. Result: Of 81/104 patients (57 females), mean age of 3813 years with sufficient data for analysis; 44% had a change in diagnosis; 26% had EEG support for non-epileptic attack disorder (NEAD); and in 30% of patients, diagnosis was unchanged. Video telemetry was less likely to lead to a change in diagnosis than ambulatory EEG, but more likely to provide support for a diagnosis of NEAD (p< 0.0001). 72 patients had reassessment of treatment, and 47% had a change in medication. Conclusion: This study highlights the influence of the ambulatory EEG in overall patient management and medication, and the role of video telemetry in diagnosis of NEAD. Based on this evidence we suggest guidelines on when to use ambulatory versus telemetry EEG in referred patients.
p698 EVALUATION OF THE UTILITY OF LONG TERM VIDEO-EEG MONITORING M. Caballero, R. Vazquez, P. M. Martinez, C. MartinezQuesada, and M. D. Jimenez University Hospital Virgen del Rocio, Sevilla, Spain
Purpose: Long-term Video-EEG monitoring is widely used for diagnosis, seizure classification and presurgical evaluation of patients with epilepsy. We evaluate the percentage of patients admitted in our video-EEG unit for diagnosis or presurgical work-up whose preadmission diagnosis and treatment was changed after video-EEG monitoring. Method: Data from a consecutive cohort of patients admitted over one year to the inpatient video-EEG unit of a tertiary hospital in Spain was retrospectively evaluated. Diagnosis and treatment of these patients before and after admission to the unit were compared. Result: 59 inpatient video-EEG monitoring studies were done during one year. Seizures have been recorded in 50 patients (84%). Preadmission diagnosis was confirmed in 39 cases (66.1%) (Including those cases for presurgical evaluations). Video-EEG monitoring results have changed the diagnosis of the type of seizure in 20 patients (33.9%). In addition, pharmacological treatment was changed after video-EEG in 25 patients (44%). Conclusion: The results of this study demonstrate that long term videoEEG monitoring is needed for the proper diagnosis and accurate treatment in patients with seizure disorders. Further studies that evaluate the cost-benefits of long-term video EEG monitoring and accurate diagnosis and pharmacological treatment are needed.

p697 INTRACRANIAL EEG SEIZURE-ONSET PATTERNS IN TEMPORAL LOBE EPILEPSY AND THEIR ASSOCIATION WITH OUTCOME, LOCALIZATION, AND HISTOLOPATHOLOGY I. Dolezalova, M. Brazdil, I. Tyrlikova, M. Hermanova, I. Rektor, and R. Kuba St. Anne's University Hospital and Faculty of Medicine, Masaryk Univerzity, Brno, Czech Republic
Purpose: We performed a retrospective study to determine the different types of seizure onset patterns (SOP) in intracranial EEG in patients with temporal lobe epilepsy (TLE). Method: We analyzed a group of 51 patients (172 seizures). We analyzed the SOP frequency during the first 3 seconds after the onset of ictal activity. The average frequency was measured. The cut-off value to distinguish between fast and slow frequency was 8 Hz. Based on these criteria, we defined three types of SOP: 1. fast ictal activity (FIA) - frequency >8 Hz; 2. slow ictal activity (SIA) - frequency <8 Hz; and 3. focal attenuation (FAT) - no clean-cut activity was present. We tried to find the relationship between SOP types and outcome of surgery (Engel I versus Engel II-IV), histopathological findings (hippocampal sclerosis, focal cortical dysplasia, other lesions and negative findings) and localization of the seizure onset zone (mesial, temporopolar, lateral). Result: In TLE patients (N=51), significantly more patients classified as Engel I had FIA and significantly fewer patients with Engel I had SIA in comparison to patients classified as Engel II-IV (p<0.001). Significantly more patients with focal cortical dysplasia had SIA in comparison to other histopathological findings (p=0.03). There were no statistically significant relationships between the SOP and the localization of the seizure onset zone. Conclusion: Our study suggests that the SOP frequency at the very early onset of epileptic seizure in patients with TLE could be a predictive factor of the outcome.
p699 APPLICATION OF DIFFUSION TENSOR IMAGING IN DRUG-RESISTANT EXTRA-TEMPORAL EPILEPSY WITH FOCAL CORTICAL DYSPLASIA IN MRI: CORRELATION WITH FDG-PET HYPOMETABOLIC AREA J. Aparicio*, A. Donaire*, X. Setoain*, S. Rub*, N. Bargall*, A. Calvo, C. Falcn, and M. Carreo* *Hospital Clnic, Barcelona, Spain; and IDIBAPS, Barcelona, Spain
Purpose: Approximately, 4050% of patients with focal epilepsy are drug-resistant and might benefit from epilepsy surgery. The detection of a brain MRI lesion increases surgical success being close to 70%. The aim was to study whether diffusion tensor MRI (DTI) is able to determine the location and extent of the lesion area (LA) in patients with extratemporal epilepsy and focal cortical dysplasia (FCD) in MRI. DTI abnormalities were correlated with the MRI and compared with hypometabolic area depicted by FDG-PET. Method: We have selected 7 patients with drug-resistant extra-temporal epilepsy and visible cerebral MRI lesion (FCD). All the patients underwent a comprehensive presurgical evaluation. The control group was composed of 30 healthy subjects. We compared the fractional anisotropy (FA) and mean diffusivity (MD) maps for each patient with the control group, one against all, by using a t-test for two independent samples. Result: It has been observed an increase in MD, mainly in the sub-cortical region behind the FCD, and a decrease in FA in the white matter tracts potentially involved in the spread of epileptic seizures. In addition, the increased MD clusters were concordant with the FDG-PET hypometabolism. Conclusion: In conclusion, DTI may be a non-invasive technique useful presurgical evaluation, because in most cases can offer complementary information about the location of the LA and the main pathways involved in seizures spread.
204 Abstracts
p700 DIAGNOSTIC ACCURACY OF [11C]-METHIONINE PET FOR THE DIFFERENTIATION BETWEEN DYSEMBRYOPLASTIC NEUROEPITHELIAL TUMOUR AND OTHER EPILEPTOGENIC BRAIN NEOPLASMS S. Rheims*, S. Rub*, E. Bernard, S. Bouvard, N. Streichenberger, M. Guenot*, and P. Ryvlin* *Hospices Civils de Lyon, Lyon, France; CERMEP-Imagerie du vivant, Lyon, France; and Hpital Neurologique, Lyon, France
Purpose: Brain tumours responsible for longstanding partial epilepsy are characterised by a high prevalence of dysembryoplastic neuroepithelial tumour (DNT), whose natural evolution is much more benign than that of gliomas. Previous studies have suggested that [11C]-methionine positron emission tomography (MET-PET) could help to distinguish DNTs from other epileptogenic brain tumours, optimising the therapeutic strategy for this type of tumour. The current study reassessed in a larger population the diagnostic accuracy of MET-PET for the differentiation between DNT and other epileptogenic brain neoplasms. Method: Retrospective study of 48 patients with partial epilepsy of at least six months duration related to a non-rapidly progressing brain tumour on MRI who underwent MET-PET. A structured visual analysis, which distinguished between normal, moderately abnormal, or markedly abnormal tumour methionine uptake, as well as various regions of interest and semiquantitative measurements were conducted. Result: Pathological results showed 20 DNTs (41.7%), 10 gangliogliomas (20.8%), 16 low-grade gliomas (33.3%) and two high-grade gliomas (4.2%). MET-PET visual findings significantly differed between the various tumour types (p<0.001), regardless of gadolinium enhancement on MRI, and were confirmed by semiquantitative analyses (p<0.001 for all calculated ratios). All gliomas and gangliogliomas were associated with moderately or markedly increased tumour methionine uptake, whereas 9/ 20 DNTs had normal methionine uptake. The only two DNT which presented with a marked MET-PET abnormality showed a specific histological pattern, including a pilocytic contingent. Conclusion: Normal MET-PET findings in patients with an epileptogenic and non-rapidly progressing brain tumour are suggestive of DNT, whereas a markedly increased tumour methionine uptake makes this diagnosis unlikely. no other specific asymmetry was established in this group of patients. Normal controls showed slight intraindividual differences in asymmetry of various white matter tracts. Hence less than ten percent side-to-side difference in different white matter tracts density should be treated with caution for the lateralization of the pathology. Conclusion: It can be concluded that fiber reduction in the fornix is the strongest tractographic sign of ipsilateral hippocampal sclerosis.
p702 SUBTRACTION ICTAL SPECT CO-REGISTERED TO MRI (SISCOM) IN CHILDREN WITH EPILEPTIC SPASMS L. Wong-Kisiel, K. Nickels, and E. Wirrell Mayo Clinic, Rochester, MN, USA
Purpose: Surgical intervention for epileptic spasms can be challenging, due to the lack of localizing EEG and MRI findings. The aim of this study is to evaluate the localizing value of SISCOM in young children with epileptic spasms. Method: Children with epileptic spasms who underwent SISCOM between January 1996 and December 2009 were identified from the Pediatric Epilepsy Monitoring Unit Database at Mayo Clinic Rochester. Children were defined as having lateralized spasms if semiology suggested focal onset. Other concurrent seizure types were recorded. Results of MRI (focal, unilateral hemispheric, bihemispheric and nonlesional) and SISCOM evaluations (localizing, nonlocalizing) were abstracted by chart review. Concordance between MRI and SISCOM was based on Epilepsy Surgery Conference report. Result: Thirteen children (median age 21 months; male 38%) with epileptic spasms were identified. All had a generalized ictal EEG correlate to their spasms. In 8 (62%), semiologic features suggesting focal onset were present. MRI brain abnormality was focal in 2 (15%), unilateral hemispheric in 4 (31%), nonlesional in 3 (23%) and bihemispheric in 4 (31%) patients. SISCOM abnormality was localizing in 6 (46%) patients, including 4 (50%) with lateralized spasms. In those with a localizing SISCOM, 2 had concordant focal MRI findings, 2 had an ipsilateral SISCOM focus with a hemispheric MRI abnormality, and two patients had bihemispheric malformations. Conclusion: Focal and lateralized MRI findings and lateralized clinical features are associated with focal SISCOM abnormalities. SISCOM can be considered in evaluating young children for epilepsy spasm when other noninvasive presurgical evaluations are unrevealing.
p701 FIBER DENSITY ASYMMETRY IN TEMPORAL LOBE EPILEPSY M. Okujava, F. Todua, M. Beraia, and T. Antia Research Institute of Clinical Medicine, Tbilisi, Georgia
Purpose: Study aimed to define most evident lateralizing signs in white matter associated with hippocampal pathology. Method: Diffusion tensor based tractography of the major white matter tracts passing temporal lobes were studied in 16 patients with hippocampal sclerosis (HS) and 15 patients with cryptogenic temporal lobe epilepsy. 30 healthy controls were studied to reveal the normal variations of the white matter side-to-side asymmetries. White matter tracts in parahippocampal gyrus, fornix, cingulum, inferior longitudinal fasciculus, uncinate fasciculus, arcuate fasciculus, external capsule and temporal pole were studied. Tract density was calculated as number of fibers passing through the given region of interest. Result: Side of the seizure origin in HS patients was strongly associated with the fiber reduction in the fornix. Less evident asymmetry was revealed for parahippocampal gyrus and temporal pole. In the group of cryptogenic TLE there was a trend of decrease of parahippocampal tracts,
p703 CONTRIBUTIONS OF EEG/FMRI TO LOCALIZING FOCAL CORTICAL DYSPLASIA F. Pittau*, L. Ferri, F. Fahoum*, F. Dubeau*, and J. Gotman* *Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada; and IRCCS Istituto delle Scienze Neurologiche, Bologna, Italy
Purpose: To examine the contribution of the BOLD response in localizing the lesion in patients with focal cortical dysplasia (FCD). Method: Patients with focal epilepsy and FCD who underwent 3T EEG/ fMRI from 2006 to 2010 were included. The diagnosis of FCD was based on neuroradiology (MRI+), or histopathology (MRI-). All underwent a 120 min recording session. IEDs similar to those recorded outside the scanner were marked in the filtered EEG. The lesion (in MRI+) or the removed cortex (in MRI-) were blindly marked on the anatomical T1 sequence, after revising the FLAIR images. For each BOLD response we assessed the concordance with the spike field and the concordance with
205 Abstracts
the lesion in MRI+ or the removed cortex in MRI-. BOLD responses were considered concordant if the maximal t-value was inside or up to 1 cm away from the marking. Result: Twenty-one patients were included (14 MRI+, 7 MRI-). In 7 patients (6 MRI+, 1 MRI-) the EEG was not active or there were artifacts during acquisition. Eight MRI+ were analyzed. In 6/8 (75%) patients at least one BOLD response had the max t value inside the lesion. Six MRIwere analyzed: in 3/6 patients the max t value was inside the removed cortex. Conclusion: BOLD responses were concordant with the lesion in 75% of patients with FCD detectable by MRI, and in 50% of patients with normal MRI. Overall EEG/fMRI is able to non-invasively localize FCD in 62.5% of cases. Supported by CIHR grant MOP-38079. Purpose: We aim to describe the psychosocial and pharmacological aspects of patients with refractory psychogenic non-epileptic seizures (PNES). Method: This was a cross-sectional study of consecutive patients with PNES referred to a Specialized Psychiatric Program from a tertiary Epilepsy Unit from January-2010 to January-2012. Refractoriness was defined as the presence of PNES despite a psychiatric treatment approach. Patients younger than 18 years-old and severe mental retardation were excluded. Result: Forty-eight patients were evaluated, 60% female. Average age was 38 (13) years-old. The time delay from the onset to the diagnostic was 8 years. Epilepsy was comorbid in 30%. PNES semiology was most likely major motor (48%), followed by minor motor (32%) and non-motor (20%). Two or more semiologies coexisted in 35%. We identified disrupted family dynamics and environmental psychosocial stressors in more than 60% of patients; despite, more than half were married, had children and 83% presented adequate family support. Professional or financial benefits were identified in 30% Psychiatric history was present in 60%. However, no major psychiatric comorbidity or risk of suicidality was found. Most frequent psychiatric disorders were depression 30%, anxiety 35% and adjustment disorder 8%. Patients were most likely treated combining two AEDs [08], Valproate (20%) and Levetiracetam (35%) were the most commonly used. After the psychiatric intervention AEDs decreased to a single one [05] that usually had psychiatric properties. Conclusion: The PNES patients profile are young adults with disrupted family dynamics and environmental psychosocial stressors. The psychiatric intervention influences the management of AEDs.
p704 HOW MUCH LANGUAGE IS IN PICTURE AND FACE PROCESSING? A. Haag, M. Centeno, J. Stretton, C. Vollmar, M. Symms, M. K. Sidhu, B. Wandschneider, P. J. Thompson, J. Duncan, and M. Koepp UCL Institute of Neurology, London, UK
Purpose: Visual naming decline can occur after left (anterior) temporal lobe (TL) resection. The risk cannot be fully predicted. Functional MRI activations during picture processing of everyday objects and unfamiliar faces were compared with a verbal (lexical) fluency (VF) task regarding activation of language areas. Method: 18 healthy controls (12 female, age: 31.46.0 years) viewed blocks of drawings of objects and unfamiliar faces during an fMRI task, and were asked to memorise them. Group activation maps were analysed on whole brain level (SPM8). Individual lateralisation indices (LIs) for the contrast pictures minus faces were compared with LIs for VF. Result: Pictures minus faces (p<.05 FWE) showed activation in the left inferior temporal gyrus (ITG; Z=6.77), and (p<.001, uncorrected) in the left inferior and superior frontal gyrus (Z=3.62; Z=5.79), which was not driven by deactivation during faces (exclusive masking). Lateralisation indices showed left>right TL activation (LI< -0.2) in 15 subjects. Lateralisation was concordant with VF in 16 (88%). Conclusion: Processing everyday objects vs. unfamiliar faces activated frontal and parts of TL language networks. Lateralisation was concordant with VF. The ITG is typically activated in response to visual language material. Activation within the left TL appeared posterior to the usual extent of TL resection in epilepsy. It remains to be shown, if naming decline can be predicted with object naming when using faces as a control condition. The paradigm may add to language lateralisation in patients struggling with VF, and can be easily applied in native language.
p706 USE OF METHYLPHENIDATE FOR ATTENTION-DEFICIT/HYPERACTIVITY DISORDER IN CHILDREN WITH AND WITHOUT EPILEPTIFORM ABNORMALITIES D. Socanski*, and A. Herigstad *Stavanger University Hospital, Division of Psychiatry, Stavanger, Norway; and Stavanger University Hospital, Stavanger, Norway
Purpose: The purpose of this retrospective study was to investigate whether epileptiform abnormalites (EAs) recorded at the attention-deficit/hyperactivity disorder (ADHD) assessment and previous history of epileptic seizures influence on initial use of methylphenidate for ADHD. Method: Subjects were 517 ADHD children (82.4%male), aged between 5 and 14 years, mean 9.5+2.6, who were diagnosed between January 2000 and December 2005. At least one standard EEG was performed on all patients. EEG findings were coded as either EEG with EAs or EEG with non-EA. The group with EAs was compared with group without EAs and the use of methylphenidate as initial pharmacological treatment for ADHD symptoms was analyzed. Result: The group with EAs consisted of 39 patients, 12 of them had previous history of epileptic seizures. Of 39 patients with EAs, 35 (89.7%) patients were initially treated with methylphenidate. The group without EAs consisted of 478 patients, 2 of them had previous history of epileptic seizures. Active epilepsy was diagnosed in 13 out of the14 patients, and 11 of the children had been seizure free for at least one year before ADHD assessment. There was no statistic difference between groups with and without EA where methylphenidate was used as initial medication for ADHD. In addition, all patients with previous epilepsy were initially treated with methylphenidate. The epilepsy comorbidity and occurrence of EAs were not a reason for not treating ADHD. Conclusion: The EsA occurrence and epilepsy co-morbidity in children diagnosed with ADHD do not cause diminished initial use of methylphenidate for ADHD.
Psychiatry and Psychology 1 Wednesday, 03 October 2012

p705 PSYCHOSOCIAL AND PSYCHOPHARMACOLOGICAL ASPECTS OF A REFRACTORY PSYCHOGENIC NONEPILEPTIC SEIZURES A. Rodriguez-Urrutia, F. J. Eiro Orosa, S. G. Fidel Kinori, E. Santamarina, X. Salas-Puig, M. V. Lopez Craver, B. Bolivares, and M. Toledo Vall dHebron University Hospital, Barcelona, Spain
206 Abstracts
p707 PERCEPTION OF SIDE-EFFECTS IN EPILEPSY PATIENTS AND DEPRESSION J. Amlerova, and P. Marusic University Hospital Motol, Prague, Czech Republic
Purpose: Side-effects of AED significantly influence quality of life in epilepsy patients. However the assessment is subjective and can be influenced by various factors. One of them can be depression which is the most frequent psychiatric comorbidity in epilepsy patients. The aim of the study was to compare the occurrence of side-effects and depression and to assess if there is any correlation between these two parameters. Method: 158 epilepsy patients were included in the study. The patients were screened for depression with the help of Beck Depression Inventory (BDI) and shortened version of depression questionnaire (NDDI-E, Gilliam F et al., 2006). The occurrence and the perception of side-effects was assessed by structured questionnaire covering both for somatic and psychical side-effects. Result: Criteria for the diagnosis of depression were met by 18% of all patients according to BDI and by 25% according to NDDI-E. Strong correlation was found between both tests (BDI, NDDI-E) Pearson corr. 0.542; p = 0.01. The most frequently reported side-effects were fatigue (58%), irritability (50%), memory impairment (46%) and dysphoria and/ or sadness (46%). These side-effects were also perceived by patients as the most significant. No correlation was found between depression and occurrence or perception of specific type of side-effect. Conclusion: Side-effects of AED and their perception seem to be not directly influenced by the level of depression. Both these variables can be considered as independent factors which significantly influence quality of life in epilepsy patients. To identify them in routine clinical setting short structured questionnaires can be used. chlorpromazine-equivalent dosage of the APDs ranged from 12.5 to 3425 mg/day (mean 454.7, SD 534.0). Conclusion: Our findings suggest that any types of APD can be used for the treatment of IIP episodes in patients with epilepsy.
p709 COMORBID DEPRESSION IN EPILEPSY SOCIODEMOGRAPHIC AND CLINICAL CORRELATES AND IMPACT ON QUALITY OF LIFE K. S. Todorova, and A. G. Kaprelyan MHAT St Marina, Varna, Bulgaria
Purpose: To investigate certain sociodemographic and clinical correlates of comorbid depression in a sample of adult Bulgarian patients with epilepsy and to assess simultaneously the role played by mood, seizurerelated and sociodemographic variables in determining their perception of QOL. Method: All 126 adult patients with a diagnosis of idiopathic epilepsy underwent clinical psychiatric examination. ILAE classification for epilepsies and epileptic syndromes was used. Comorbid depressive disorder was diagnosed according to ICD-10 diagnostic criteria, followed by evaluation on Hamilton Depression Rating Scale (HAM-D-17). Self-assesment scales were administered: Seizure Severity Questionnaire (SSQ) and Quality of Life in Epilepsy Inventory-31 (QOLIE-31). A questionnaire for demographic and seizure-related variables was completed. Univariate and multivariate regression analyses were performed to explore the association between possible prognostic independent variables and QOLIE-31 overall and subscale scores. Result: Comorbid depressive disorder affected 36(28.6%) of all evaluated patients. Education, seizure severity and duration of epilepsy correlated significantly with comorbid depression. Following the univariate analysis education, employability and age, seizure severity and seizure frequency and the severity of the comorbid depressive disorder were the variables significantly correlated with QOLIE-31 overall score (p<0.01). A three variable model accounted for 74% of the variance for QOLIE-31 overall score including seizure severity, comorbid depression and seizure frequency. Conclusion: Comorbid depressive disorder in a sample of adult Bulgarian patients with epilepsy was associated with low education, severe seizures and longer duration of epilepsy. Detection and treatment of psychiatric comorbidity in epilepsy is a challenge for improving the quality of life of the affected patients.
p708 DURATION OF INTERICTAL PSYCHOTIC EPISODES BY ANTIPSYCHOTIC DRUG TREATMENTS K. Hara*, N. Adachi, N. Akanuma, M. Okazaki, M. Ito, M. Kato**, and T. Onuma** *Asai Hospital, Togane, Japan; Adachi Mental Clinic, Sapporo, Japan; South London and Maudley NHS Foundation Trust, London, UK; National Center Hospital of Neurology and Psychiatry, Kodaira, Japan; Jozen Mental Clinic, Sapporo, Japan; and **Musashino Kokubnji Clinic, Kokubunji, Japan
Purpose: Patients with epilepsy often suffer from coexisting interictal psychotic (IIP) symptoms. However, the treatment systems of these phenomena have not been well established due to insufficient evidence. We retrospectively investigated relation between duration of IIP episode and antipsychotic drug (APD) treatments. Method: In our adult epilepsy clinics, 155 patients with epilepsy (age of onset of epilepsy was mean 12.4 years; epilepsy types comprised 25 generalized epilepsy and 130 partial epilepsy) exhibited 320 IIP episodes (age of the psychotic episodes was mean 30.9 years). Duration of these IIP episodes was retrospectively analysed. The APD treatments of the 320 IIP episodes comprised four groups: 242 episodes were treated with typical APDs (Typical group), 15 with atypical APDs (Atypical group), 15 with both typical and atypical APDs (Mixed group), and 48 were not treated with APD (Non-APD group). The dosage of APDs undertaken was converted into chlorpromazine equivalent. Result: Duration of the IIP episodes were mean 82.7 weeks. There was no significant difference in the duration of IIP episodes between the four treatment group; Typical group lasted for mean 91.8 weeks, Atypical group for 101.5 weeks, Mixed group for 90.5 weeks, Non-APD group for 28.9 weeks (F=1.46, p=0.224). In 272 episodes treated with APDs, a total
p710 PSHYCHIATRIC FEATURES IN FAMILIES WITH AUTOSOMAL DOMINANT CORTICAL TREMOR, MYOCLONUS AND EPILEPSY L. Santulli, A. Coppola, C. Caccavale, C. Ciampa, P. Striano, and S. Striano Epilepsy Center Federico II, Naples, Italy
Purpose: Autosomal Dominant Cortical Tremor, Myoclonus and Epilepsy (ADCME) is an inherited condition characterized by familial occurrence of cortical tremor, myoclonus and epileptic seizures. We have recently reported a relatively high frequency (>40% of the cases) of pshychiatric symptoms clinically defined (i e generalized anxiety disorder and depression) in a large series of patients. Aim of this study is to further assess pshychiatric comorbidity in a subgroup of ADCME/BAFME patients by using reliable and valid pshycodiagnostic scales. Method: Thirteen patients underwent self administered tests: BDI (Beck Depression Inventory), STAI-Y (State-Trait Anxiety Inventory Y), MMPI-2 (Minnesota Multiphasic Personality Inventory-2) and QoLIE31 (Quality-of-Life in Epilepsy Inventory), and a pshychiatric interview.
207 Abstracts
Result: Severe to mild depression symptoms were present in almost all the patients whereas a clinically relevant anxiety disorder was evident in eight. MMPI-2 results supported the coexistence of a personality disorder in seven patients. Quality of life scores were lower than previously reported in Italian epileptic patients. Conclusion: This pilot study firstly confirms a high incidence of mood disorders, particularly depression and anxiety, in ADCME patients, often associated to pathological traits of personality. Moreover these patients show a worse quality of life compared to other patients presenting only with seizures, probably due to the influence of tremor on daily life activities. Purpose: To identify associated factors with the development of forced normalization (FN) in post-surgical patients of temporal lobectomy (TL) with medically intractable epilepsy (MIE). Method: A cohort study analytical-descriptive, retrospective, we selected 248 medical records of patients who met epilepsy surgery protocols, 22 of which showed disappearance of seizures with alternating psychiatric disorders after postsurgical TL, we divided group 1 with the ones who presented FN and those who did not have these features were classified as group 2. Result: Group 1 showed a percentage of (77.2%) with tendency to female predominance (p <0.05), group 2 obtained (50.44%) (p <0.05) 95% CI (1.471.59). In the FN group, 19 cases (86.4%) were detected in patients with duration of epilepsy greater than 10 years and 168 (74.3%) in group 2. Psychosis and depression predominated with a distribution of group 1 (54.5%) SD + / - 1.43, (p> 0.05) and group 2 (5.8%), SD + / - 1.50, (p>0.05) 95% CI (4.875.32). For epileptiform activity, the discharges were identified bilateral in group 1 (90.9%) + / 0.29 (p> 0.05), group 2 (20.8%), SD + / - 0.40, (p <0.05) 95% CI (1.21 1.33). Conclusion: The forced normalization phenomenon is related to the time course of epilepsy (more than 10 years), predominantly in the female gender and with a psychopathology of both psychotic and depressive type. Bilateral epileptiform discharges constitutes another finding to take into account, suggesting that psychiatric alterations are masked by epilepsy, manifesting themselves in order to gain control of it.
p711 INFLUENCE OF PSYCHOPATHOLOGIC SYMPTOMS ON QUALITY OF LIFE IN PATIENTS WITH EPILEPSY M. Milovanovic, Z. Martinovic, V. Radivojevic, M. Jovanovic, N. Buder, and R. Djokic Institute for Mental Health, Belgrade, Serbia
Purpose: To assess psychopathologic symptoms in patients with epilepsy and to define its influence on quality of life (QOL). Method: Adult patients (age range 1865 years) with epilepsy of normal intelligence, without any progressive neurological disease or psychotic disorder were included in the study. They completed The Symptom Checklist-90-Revised (SCL-90-R) - self-report multidimensional questionnaire designed to screen psychological problems, and Quality of life in epilepsy Inventory (QOLIE-31 - Serbian validated version; Seizure, 2010). Results: 202 patients completed the questionnaires. Compared to patients with primarily generalized epilepsies, patients with localizationrelated epilepsies showed significantly higher scores on SCL-90 primary symptom dimensions: Somatization, Obsessive-Compulsive, Interpersonal Sensitivity, Depression, Anxiety, Hostility, Phobic Anxiety, Paranoid Ideation, and Psychoticism (t=2.283.66; p=0.0250.000). Oneway ANOVA showed that Obsessive-Compulsive, Interpersonal Sensitivity, Depression, Anxiety, Hostility, Paranoid Ideation, and Psychoticism scales were higher in patients with high seizure severity index (F=2.7934.286; p=0.0430.006). QOLIE-31 scales: Overall quality of life, Emotional well being, Fatigue, Cognitive and Social function were significantly negatively correlated to all SCL-90 scales (rho=-0.745, p<0.001). Also, there was negative correlation between QOLIE-31 Medication effect scale and SCL -90 Obsessive-Compulsive and Psychoticism scales. Multiple regression analysis showed that 49.4% of overall QOLIE-31 score was predicted by SCL-90 scales (F=11.4; p<0.001; R2= 0.494). Tests of regression coefficients significance showed that Obsessive-Compulsive scale score (beta =-0.28; t=-1.99; p<0.05) and depression scale score (beta =-0.43; t=-2.69; p<0.01) were significant predictors of quality of life. Conclusion: Psychopathologic symptoms frequently coexist in patients with localization-related epilepsy, with high seizure severity, and have significant influence on QOL.
p713 ARE PSYCHIATRIC DISORDERS EXCLUSION CRITERIA FOR VIDEO EEG MONITORING AND EPILEPSY SURGERY IN PATIENTS WITH MESIAL TEMPORAL SCLEROSIS? P. O. Da Conceio, P. P. Do Nascimento, N. B. Alonso, E. M. T. Yacubian, and G. M. De Arajo Filho Universidade Federal De Sao Paulo UNIFESP, So Paulo, SP, Brazil
Purpose: Epilepsy surgery (ES) is a treatment option for patients with refractory temporal lobe epilepsy (TLE). However, psychiatric disorders (PD) have been a contraindication for pre-surgical evaluation and surgeryin many epilepsy centers. The aim of this study was to evaluated safety of Video EEG (VEEG) and surgical outcome in patients with refractory TLE and mesial temporal sclerosis (TLE-MTS) associated with PD. Method: We retrospectively analyzed clinical, sociodemographic, VEEG data and surgery outcome from patients with refractory TLEMTS who underwent ES over the period of 2002 to 2011, and compared the data between patients with and without PD. Psychiatric evaluation was performed through DSM-IV criteria. Safety during pre-surgical evaluation was analyzed by the rate of adverse events (AEs), and the surgical outcome was measured through Engel's classification. Result: We evaluated 145 patients (82 females, mean age 37.8 years, range 1863), 61 with PD. The mean of stay in VEEG was 99.66 hours and was not affected by PD. In patients with PD, 4.91% (3/61) had AEs, 13.11% (8/61) had nonepileptic attack disorders (NEADs). Among patients without PD, 4.76%(4/84) had AEs and 5.95% (5/84) had NEADs. In the first two years of follow up in 94 patients who underwent ES, 65.85% (27/41) with PD and 67.92% (36/53) of group without PD became free of disabling seizures (Engel I). Conclusion: These data demonstrate that the rate of AEs and the seizure outcome did not differ significantly between both groups, reinforcing that PD should not be absolute exclusion criteria for VEEG monitoring and epilepsy surgery.
p712 FORCED NORMALIZATION IN POST-SURGICAL PATIENTS OF TEMPORAL LOBECTOMY AND MEDICALLY INTRACTABLE EPILEPSY. COLOMBIAN FOUNDATION CENTER FOR EPILEPSY AND NEUROLOGICAL DISEASES FIRE M. Z. Torres, E. V. Perea, J. Fandio-Franky, L. V. Polo, R. O. Guerra, S. C. Pia, J. C. I. Benedetti, O. B. Cabarcas, D. J. Jimenez, E. C. Garcia, and T. Y. Rodriguez Colombian Foundation Centre for Epilepsy and Neurological Diseases, Cartagena, Colombia
208 Abstracts
p714 MOOD DYSFUNCTION IN EPILEPSY PATIENTS IN KOSOVO V. Govori*, S. Vranica*, M. Berisha, B. Berisha*, and D. Zajmi *University Clinical Center of Kosovo, Pristina Kosovo, Albania; and National Institute of Public Health of Kosovo, Pristina Kosovo, Albania
Purpose: Mood disorders are the most frequent psychiatric co morbidity in epilepsy. The aim of this study is to determine the presence of depressive symptoms in epilepsy patients. Method: In this prospective study, 76 consecutive outpatients with active epilepsy were examined in the Department of Neurology of Kosovo during 2011. Clinical data for patients included age, gender, seizure type, education, employment, marital status. The epilepsy evaluation was done on standard digital EEG recordings. We used the Beck Depression Inventory test to evaluate depressive symptoms in patients with epilepsy. The test contained 21 questions each answer being scored on scale value of 0 to 3. Scores of 1115 are indicative of mild, 1624 of moderate, and 24 of severe depression. All data collected were analyzed and calculated relevant statistical parameters and tests for the level of significance for P<0.01 and P<0.05. Result: From 76 patients with epilepsy 52% were male, average age was 33.4 13.54. Partial type of epilepsy in 64.0% of cases, severe depressive symptoms in 32.0% and moderate depressive symptoms in 29.3%, 12.0% think about suicide but had not made, with statistical significance for P<0.05. From overall number of examined outpatients with epilepsy, unemployed were in 89.3% of cases with statistical significance for P<0.0001. Conclusion: Our study suggests that patients with epilepsy are at increased risk for depression, vigilant approach and early treatment is needed. Conclusion: On the whole children with a history of PFS have memory abilities that place them within the normal range and are tightly linked to their intellectual abilities. Isolated cases where there are indications of specific memory impairments need to be evaluated further to establish whether this is of clinical importance.

p716 RHYTHMIC TREMOR ARTIFACT MIMICKING ICTAL EPILEPTIFORM PATTERN ON EEG OF NON-EPILEPTIC PSYCHOGENIC SEIZURES T. Tombul, and A. Milanlioglu Yznc Yil Universty, Van, Turkey
Purpose: Psychogenic seizures are events which observed commonly in non-epileptic seizures, and can be confused with epileptic seizures interms of motor phenomena when an adequate clinical and electrophysiological assessment are not done. In our study, we aimed to determine characteristics of EEG that can be mixed confused with ictal epileptiform activities of non-epileptic psychogenic seizures characterized by rhythmic movements similar to tremor. Method: The cases with non-epileptic psychogenic seizures having like clonic convulsions, rhythmic movements evaluated clinically and based on electrophysiological characteristics. Five cases, three men and two women, aged between 33 and 54, were included into the present study. Result: Three of these cases had only psychogenic, and the remaining had both psychogenic and complex partial type of epileptic seizures. In ictal recordings, rhythmic tremor artifacts that were similar to seizure activity composed of sharp-contoured theta waves were recognized. This pattern was appeared by theta-like activity with stable frequency, sudden onset/offset without building-up and postictal slowing. In synchronized video recordings, rhythmic tremor movements which were similar to clonic contractions were demonstrated at upper and lower extremities, and sometimes at the head and trunk. Conclusion: Psychogenic seizures may be characterized by rhythmic movements that are similar to clonic contractions, and the activity observed in the meantime may mimic ictal discharges observed in the epileptic seizures. However, the frequency of electrophysiologic pattern of non-epileptic seizures showed narrow interval changes and most of the time remained stable. In such cases, the detailed semiological and electrophysiological evaluation with a large number of seizure recordings are important.
p715 MEMORY DEVELOPMENT IN CHILDREN WITH A HISTORY OF PROLONGED FEBRILE SEIZURES M. Martinos, S. Pujar, H. OReilly, R. Scott, R. Chin, and M. De Haan UCL, London, UK
Purpose: Retrospective studies have highlighted an association between hippocampal sclerosis and a childhood history of prolonged febrile seizures (PFS). Given the well established role of the hippocampus in memory, we would therefore hypothesize that memory impairments may be present in children with a history of PFS. Method: We are recruiting children with a history of PFS originally identified by the population-based North London Convulsive Status Epilepticus in childhood surveillance study (NLSTEPSS). Upon recruitment children undergo detailed investigations to determine their longer-term outcome 610 years following their episode. Memory abilities are assessed using the Children's Memory Scale (CMS) and full scale IQ (FSIQ) is assessed using the Wechsler Abbreviated Scale of Intelligence (WASI). Result: Nineteen children (mean age: 9 years) have so far completed a full set of investigations a mean of 7.21 years following their episode. Their general memory quotient falls within the normal range (mean: 103.7), and is highly correlated with their FSIQ (r=0.595, p=0.007). In 3 children, there is evidence of statistically significant discrepancies between their visual and their verbal memory domains pointing to the possibility of structural abnormalities. Finally, one child was found to be clinically impaired in their immediate and delayed verbal memory abilities.
p717 DO ANTIPSYCHOTIC DRUGS INCREASE SEIZURE FREQUENCY IN EPILEPSY PATIENTS? M. Okazaki*, N. Adachi, M. Ito, M. Watanabe*, Y. Watanabe*, M. Kato, and T. Onuma *National Center Hospital of Neurology and Psychiatry, Kodaira, Japan; Adachi Mental Clinic, Sapporo, Japan; Jozen Mental Clinic, Sapporo, Japan; and Musashino Kokubnji Clinic, Kokubunji, Japan
Purpose: Patients with epilepsy could suffer psychosis and related conditions. It is sometimes difficult to use anti-psychotic drugs (APDs) for
209 Abstracts
the treatment of these conditions, because APDs may have risks to aggravate seizures. However, evidence whether the treatment with APDs increases seizure frequency significantly in epilepsy patients who are already being treated with antiepileptic drugs (AEDs) is scarce. To investigate the clinical effects of APDs on the seizure frequency of epilepsy patients, we retrospectively evaluated the one-year prognosis of seizure frequencies. Method: The subjects of the study were 142 epilepsy patients treated with APDs (typical APD in 107, atypical APDs in 68 and combination in 33) and 291 age-, age at onset of epilepsy- and epilepsy typematched epilepsy patients without APD treatment. Seizure frequencies in a oneyear period after administration of APDs were retrospectively evaluated and compared with those of the controls. Result: In the epilepsy patients with APDs, the seizure frequencies at four observation points (1-, 3-, 6-, and 12-months after their administration of APDs were lower than those of the same four age-matched periods of the control group. There was no significant difference in seizure frequencies among typical APDs, atypical APDs, and the combination of typical/atypical APDs. In epilepsy patients treated with AEDs, APDs are unlikely to exacerbate seizures. Most APDs, either typical or atypical, can be used for psychiatric treatment in epilepsy patients.
p719 INTERICTAL DYSPHORIC DISORDER IN JAPANESE PATIENTS WITH LOCALIZATION-RELATED EPILEPSY: PREVALENCE AND CLINICAL CHARACTERISTICS A. Yoshino, Y. Tatsuzawa, T. Mogi, T. Suda, and S. Nomura National Defense Medical College, Tokorozawa, Japan
Purpose: Researchers in European countries and the United State suggested the occurrence of a pleomorphic affective syndrome in patients with epilepsy named interictal dysphoric disorder (IDD). We estimated the prevalence of IDD in Japanese patients with localization-related epilepsy using the Japanese version of the Interictal Dysphoric Disorder Inventory (IDDI, Mula et al., 2008) and investigated the clinical characteristics of IDD. Method: Eighty-seven patients with localization-related epilepsy (median age 39 years; female, 39) were assessed using IDDI, Quality of Life26 (WHO-QOL26), Hamilton Depression Rating Scale (HAM-D), Adverse Events Profile (AEP), and Mini Mental State Examination (MMSE). Diagnosis of current and lifetime psychiatric disorders was established using the Mini International Neuropsychiatric Interview (MINI). We also evaluated to what extent IDD and premenstrual dysphoric disorder (PMDD) overlapped. Result: The internal consistency of the Japanese version of IDDI was fairly good (Cronbach's alpha, 079). The prevalence rate of IDD was estimated 38.0% without sex difference. Only 13.3% of the female patients with IDD met the criteria of PMDD. Compared with the patient without IDD, the patients with IDD were more likely to have any current and lifetime psychiatric disorders (lifetime, 60.6% vs. 33.3%). WHO-QOL26 score was significantly less and HAM-D and AEP scores were significantly greater in the patients with IDD. However, the seizure-free rate and MMSE score were not different between patients with and without IDD. Conclusion: These results suggest that more than one third of patients with localization-related epilepsy suffer from IDD which might impair their QOL and have some clinical and psychopathological characteristics.
p718 PSYCHOGENIC NON EPILEPTIC SEIZURES: THE NIDUS MAY LIE SOMEWHERE ELSE S. Kumar*, and P. K. Singh *CSMMU (Erstwhile King George's Medical College), Lucknow, Patna, India; and Patna Medical College, Patna, India
Purpose: Psychogenic Non Epileptic Seizures (PNES) has gradually lost its place from the body of literature in the developed world. But the importance of diagnosis and management of the conditions can't be undermined. The condition is often misdiagnosed even at the tertiary care centres. The co-morbidities associated with PNES is often ignored due to the dramatic nature of the presentation of the illness, by even the most experienced clinicians. The study aimed at finding the co-morbid illnesses which often form the background of the illnesses. Having the understanding of the co-morbid condition can be crucial to the management as it may save the health costs and prevent the unnecessary institution of the medications. The nature of the stress can vary across the boundaries but not the phenomenology or the associated psychopathology in case of PNES. Method: Fifty consenting patients diagnosed with Non Epileptic Seizures who attended psychiatry OPD of Patna Medical College, Bihar, India were assessed for co-morbidities clinically and history was also obtained from closely living family member of the patient. Eighty percent of the patients were found to be harbouring co morbid psychiatric illnesses. Most common being Depression followed by Anxiety disorders. The other disorders present included Adjustment Disorder, Personality disorders and rarely Psychosis. Result: It was inferred that Co-morbid Psychiatric illnesses are commonly associated with Non Epileptic Seizures. Finding and treating the Co-morbid Psychiatric illnesses can help formulating effective management strategies and hence better outcomes in patient with Psychogenic Non Epileptic Seizure Disorder. Conclusion: The presentation and hence the diagnosis of PNES can be deceptive. Understanding the phenomenology and the underlying psychopathology is important for avoiding the possible error of judgment and managing the same. The series revealed co-morbid psychopathology in sizeable no of patients suffering from PNES.
p720 PREVALENCE OF SYMPTOMS OF INTERICTAL DYSPHORIC DISORDER: RESULTS OF A SURVEY CONDUCTED AT THE WELSH EPILEPSY UNIT C. B. Kuloor*, and Z. Ahmed *South London & Maudsley NHS Foundation Trust, London, UK; and University Hospital of Wales, Cardiff, UK
Purpose: Interictal Dysphoric Disorder (IDD) is considered to be a common yet under-diagnosed neuropsychiatric disorder in epilepsy. The aim of this study was to explore the prevalence of individual symptoms of Interictal Dysphoric Disorder among patients with epilepsy attending a specialist epilepsy unit. Method: One hundred two consecutive adult patients with epilepsy were invited to complete the Interictal Dysphoric Disorder Inventory, a 38-item self-report questionnaire. Patients with an established psychiatric diagnosis or co-morbid medical conditions with symptoms resembling those of IDD and patients with special needs were excluded from this study. Result: Eighty-eight patients completed the questionnaire (response rate of 86%). Most patients had experienced at least one symptom of IDD of significant severity over the previous 12 months. Anergia was the most commonly reported symptom (prevalence rate of 56%), followed by irritability (47%), anxiety (41%), pain (41%), fear (41%), depressed mood (40%), and insomnia (34%). Euphoric mood was the least reported symptom (10%). Nearly 24% of patients fulfilled the criteria for a diagnosis of IDD. Furthermore, one in four patients recognised a temporal relationship between changes to their anti-epileptic drug (AED) therapy and the emergence of symptoms of IDD.
210 Abstracts
Conclusion: Symptoms of IDD are prevalent among patients with epilepsy and may go unrecognised. The prevalence rate for IDD in our study was higher than the rate reported in the only other cross-sectional study previously conducted. Effect of changes to AED therapy on the emergence of symptoms of IDD warrants further exploration. asthenia. There was an association between higher baseline seizure frequency and higher scores in the Suspicion Scale for TLE patients. The shifts in T-score mean levels from baseline to the two year follow-up were all within the normal range. Conclusion: In this cohort, even though group levels were normal a substantial number of patients had psychological problems. The main longitudinal result was that the personality features were stable and did not change after epilepsy surgery.
p721 QUALITY OF LIFE IN CHILDHOOD EPILEPSY AND PARENTAL AND PAEDIATRIC ANXIETY: THE ROLE OF A STRUCTURED EDUCATION PROGRAM G. Serdaroglu, S. Sahin, B. Ozbaran, S. Yilmaz, A. Akcay, H. Tekgul, and S. Gokben Ege University Faculty of Medicine, Izmir, Turkey
Purpose: To determine whether a structured education program can change anxiety and quality of life in children with epilepsy, and reduce parental anxiety. Method: Three groups were included: Group I, 6 - 18 year old newly diagnosed epilepsy patients; Group II, patients with epilepsy having followed-up and on antiepileptic therapy for at least 1 year; Group III, patients with intractable epilepsy. Questionnaires were applied before and 6 months after a program of education in the first group. Applied tests were; questionnaires about epilepsy, anxiety scales (State-Trait Anxiety Inventory, Anxiety Scale for Children for the child), Quality of Life Scales and the Child Behavior Check List. These tests were also applied to the children in Groups II and III during their outpatient clinic visit. Result: Seventy-two epileptic children and their parents were included in the study. Post-education scores of Group I were higher than their pre-education scores and the scores of the other 2 groups. After education, a significant decrement was seen both in state and trait scores of the State-Trait Anxiety Inventory which evaluated parental anxiety. Anxiety Scale for Children had also a decrement for Group I after education. Child Quality of Life Scales were evaluated. Scale Total Scores and Psychosocial Health Total Scores were significantly higher in the post-education assessment when compared to the pre-education assessment for Group I. Conclusion: Giving information about epilepsy will decrease anxiety levels, increase drug compliance and possibly provide better seizure control in children with epilepsy.
p723 THE EFFECTS OF SUPPORT GROUP ON SELFESTEEM IN PEOPLE WITH EPILEPSY S. Tiamkao*, K. Sawanchareon, and S. Pranboon *Integrated Epilepsy Research Group, Khon Kaen University, Khon Kaen, Thailand; KhonKaen University, KhonKaen, Thailand; and Srinagarind Hospital, KhonKaen University, KhonKaen, Thailand
Purpose: People with epilepsy (PWE) have to face physical and mental illness, and social stigma, which affect their self esteem and quality of life. Objective: The purpose of this study was to examine the effects of a support group on self-esteem in PWE. Method: A Quasi-experimental study was performed of 120 PWE in an Epilepsy Clinic at Srinagarind Hospital. An experimental group (N=60) attended in the support group before receiving regular healthcare services. The control group (N=60) received only regular healthcare services. Data was collected by using the Rosenberg self -esteem scale scoring before and after the experiment. The score was analyzed by using a paired t-test and an independent t-test. Results: The study showed that before the experiment, the self esteem score of the control group was significantly higher than the experimental group (= 35.06, 32.80, t = 2.38 P < .05). After the experiment, the score of the control group and the experimental group were showed a significant statistical difference (= 3.06, 34.30, t = -6.61 P < .05). The score in the control group was significantly lower than the experimental group (= 35.01, 30.60, t = 9.97 P < .05), while the score in the experimental group was significantly higher than before the experiment (= 32.80, 34.30, t = 2.19 P < .05) Conclusions: The support group improves in self- esteem in PWE. Medical personnel should set up a support group for PWE to enhance their self-esteem.
p722 A LONGITUDINAL STUDY OF PSYCHOLOGICAL FEATURES IN PATIENTS BEFORE AND 2 YEARS AFTER EPILEPSY SURGERY K. Malmgren, and E. Engman Sahlgrenska Academy, University of Gothenburg, Gteborg, Sweden
Purpose: There are few consistent findings concerning psychological and personality features in patients with drug resistant epilepsy. This study aimed at investigating psychological features in patients before and two years after epilepsy surgery. Method: Fifty patients, 39 with temporal lobe epilepsy (TLE) and 11 with frontal lobe epilepsy (FLE) were assessed at baseline and two years postoperatively with the Karolinska Scales of Personality (KSP). This inventory consists of 15 scales (135 items). Each item is given a statement with four-point Likert scale response format with normative data based on a large random healthy adult sample of 400 men and women. Result: Baseline group level outcome was normal, while individual level analyses delineated psychological problems outside the normal range in subsets of patients. Features of hostility characterised half of the FLE and one fourth of the TLE patients. Above 1/3 in each group had dependency features. About 1/3 of the TLE patients suffered from psychEpilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x
p724 COGNITIVE RETRAINING AMONG CHILDREN WITH EPILEPSY AT A TERTIARY CARE HOSPITAL IN DELHI, INDIA K. Bala, V. Sharma, and N. Verma Institute of Human Behaviour and Allied Sciences, Delhi, India
Purpose: Current study was an attempt to find out the effect of cognitive retaining on the most commonly affected cognitive domains ie. attention and memory among children with epilepsy receiving AEDs. Method: Children diagnosed with idiopathic epilepsy were selected from outpatient department of neurology at IHBAS. Participants were divided in to two experimental groups and a waitlist control group. Group A (ongoing seizure), group B (seizure free), group C (wait list control group). All these children were assessed on various domains of attention and memory. Between pre and post assessment they were provided with a package of 24 sessions of cognitive retraining: Result: Findings revealed no significant difference in the cognitive skills of the children among three groups in pre intervention condition
211 Abstracts
except for sustained attention Post intervention condition of experimental groups resulted in significant improvement in most of the cognitive skills. No such gains were observed for the wait list control group. It was observed that children with seizure free condition performed better on assessment and showed higher gain from cognitive retraining as compared to those with ongoing seizures. Conclusion: It was inferred that manualized cognitive retraining package is an effective module for enhancing cognitive skills of children suffering from cognitive deficits resulting from epilepsy. Conclusion: The study inference was that manulisized cognitive retraining package is an effective module for enhancing cognitive skills of children suffering from cognitive defecits associated with epilepsy. performed in a German patient cohort, STL in a French group. The surgical procedure was performed since it had been standard in each centre. Method: We retrospectively recruited 60 adult patients with medically refractory mTLE with unilateral hippocampal sclerosis which had justified temporal lobe surgery between 2000 and 2009 and were seizure free after resection. Neuropsychological assessments were performed in all these patients on three different occasions by using parallel versions of standardized neuropsychological tests (preoperatively, 1 year postoperatively and on average 7 years postoperatively). Result: On the 7 years postoperative examination, SAH patients had significantly better performances than STL patients concerning visual learning and delayed recall, verbal and visual short term memory and visual working memory. Conclusion: SAH appears to be the best surgical method to treat drugresistant mesio-TLE with unilateral hippocampal sclerosis in regarding long term memory function.
p725 ONLINE ASSESSMENT OF REMOTE AND SEMANTIC MEMORY IN EPILEPSY BY USING DAILY NEWS QUESTIONNAIRES M. Hendriks*, T. Lunenburg, and M. Meeter *Epilepsy Centre Kempenhaeghe, Heeze, The Netherlands; Radboud University Nijmegen, Nijmegen, The Netherlands; and Free University, Amsterdam, The Netherlands
Purpose: Although anterograde memory deficits are well documented in patients with epilepsy, the extent to which remote memory deficits occur is less clear. This is due in part to a lack of reliable methods for assessment. A common method to assess remote memory is an autobiographical memory test. The primary purpose of this study is to compare remote, semantic memory in patients with epilepsy and healthy controls. Method: In cooperation with the Dutch Epilepsy Society (EVN) in total 420 epilepsy patients and 260 healthy controls logged in at the EVN website to fill in the Amsterdam Media Questionnaire (AMQ) and the Daily News Memory Test (DNMT) (Meeter, et al, 2004, 2005). 509 Participants (age between 16 and 83) were included to the DNMT sample and 429 Participants (age between 24 and 83) were included to the AMQ sample. Paticipants had to anwer the questionnaires per decade after their seizure onset. Result: The results show that healthy Controls score significantly better on the AMQ compared to Epilepsy Patients (F(1,164) = 14.864, p<.001, v2=.083. Healthy Controls score significantly better for all 3 decades of the DNMT compared to Epilepsy Patients (F(1,503) = 8.392, p=.004, v2=.16). An ANCOVA did not show statistically significant effects of the epilepsy related factors. Conclusion: This study demonstrates memory problems for news facts in patients with epilepsy. We found no evidence for epilepsy related factors with remote memory. The results of the current study show a problem in the recall of memories.

p727 TYPES OF COPING STRATEGIES FOR EPILEPTIC PATIENTS L. Lipatova, L. Vasserman, and A. Chuykova St.Petersburg V.M. Bekhterev Psychoneurological Research Institute, St. Petersburg, Russian Federation
Purpose: Explore the types of coping strategies (CS) for epileptic patients (EP) to overcome difficult situations in the different areas of life. Method: 139 EP aged 19 to 65 years (72 women and 67 men) were examined with a CS test (Lazarus R.S., Folkman S., 1986; Vasserman L.I. et al., 2009). Result: EP most frequently used CS options that facilitated successful adaptation and expressed in individual's active behavior towards resolving difficult situations: problem solving (62%), seeking social support (60%), exercising self-control (59%), accepting responsibility (53%) and positive reappraisal (49%). Maladaptive CS types were less common for EP confrontation in 42%, distancing 41% and escape-avoidance -38%. Differences in CS between male and female patients were revealed: men more frequently than women took the strategies of accepting responsibility (60% and 44% respectively), positive reappraisal (58% and 52%) and problem solving (67% and 62%), however, they were more likely to distance (50% and 45%). Women on the other hand were more likely to use maladaptive emotional and behavioral CS confrontation (51% women, 42.9% - men) and escape-avoidance (44% and 41% respectively). Conclusion: EP use a wide range of CS: from active strategies aimed at analyzing and resolving problems as they occur, to passive forms of behavior that contribute to continuous emotional stress and problem avoidance. Besides the presence of gender-specific choices of CS this study shows the prevalence of the EP with adaptive forms of coping behavior aimed at the collaboration with the attending doctor and facilitating social adaptation.
p726 LONG TERM MEMORY OUTCOME AFTER SELECTIVE AMYGDALOHIPPOCAMPECTOMY VERSUS STANDARD TEMPORAL LOBECTOMY IN TEMPORAL LOBE EPILEPSY A. Wendling, I. Wisniewski, C. Davanture, J. Zentner, S. Bilic, A. M. Staack, M. Valenti, A. Schulze-Bonhage, P. Kehrli, E. Hirsch, and B. J. Steinhoff Kork Epilepsy Centre, Kork, Germany
Purpose: To investigate the long term follow-up after selective amydalohippocampectomy (SAH) and standardized temporal lobectomy (STL), respectively, in two homogeneous patient groups with clearly defined unilateral mesial temporal lobe epilepsy (mTLE). SAH was
p728 COGNITIVE IMPAIRMENT AND COGNITIVE EVOKED POTENTIALS IN PATIENTS WITH PARTIAL SYMPTOMATIC EPILEPSY A. Kostylev, and N. V. Pizova
212 Abstracts
Clinical Hospital # 8 of Yaroslavl, Yaroslavl, Russian Federation
Purpose: Cognitive impairment among the most frequent changes accompanying chronic epilepsy. P300 is the neuronal correlation for the attention, short term memory and decision making attitude. It is interesting possible relationship between neuropsychological and neurophysiological tests in patients with epilepsy. Method: We investigated 37 patients (20 women and 17 men), mean age 32 4 years. Patients had partial symptomatic epilepsy with motor seizures and GTCS. Age of the disease was 9 3 years. The frequency of seizures per month was 3 2. Patients were treated with standard antiepileptic drugs. Patients did not have depression (Tsung scale). For cognitive auditory evoked potential we used odd-ball paradigm, the active electrode at the CZ, the reference electrode M1/M2. We measured the peak latency of P300 in a superposition of two curves. For the study of cognitive impairment was used standart memory for digits test (memorizing 12 digits in 1 minute). Result: In patients with epilepsy found increased latency of P300 peak with increasing age (p <0.001), as well as in healthy (aging curve, Polish 1993). The latency of the peak for patients with epilepsy compared to the normative data for healthy was higher, but this change was not significant. It was found that the less correct answers given during the test memory of digits the higher the peak latency of P300 (P <0.005). Conclusion: According to our data, may be a possible link neuropsychological and neurophysiological changes in patients with epilepsy, but it takes a larger sample and the control group.
p730 IS PROPOFOL TOLERABLE DURING WADA? F. Alsallom, S. Sinha, S. Wahaas, A. Benito, F. Alsenani, F. Bamogaddam, and K. A. Siddiqui National Neurosciences Institute, King Fahad Medical City, Riyadh, Saudi Arabia
Purpose: WADA test helps in pre-surgical evaluation of epileptic patients, specifically, predicting the post surgical outcome for language and memory. Sodium Amytal (SA) was by far the most commonly used agent for this purpose. Lack of availability of SA had initiated the use of Propofol (PF). We assessed the tolerability of PF for WADA testing. Method: We retrospectively reviewed the data of 9 patients who had WADA testing done. All had temporal lobe epilepsy (TLE) and were surgical candidates of temporal lobectomy. PF was utilized for WADA procedure. Result: Nine patients with mean (+SD) age 26(+5.8) years, 6 males and 3 females were recruited. Six of them had left TLE, and 3 of them had right TLE. In each patient, neurointerventionalist injected 10 mg of PF in the Internal Carotid Artery (ICA) via a catheter inserted through a puncture site at the right femoral artery. Right hemispheric injection followed by left hemisphere injection after 30 minutes. During the procedure, EEG monitoring showed changes within 518 seconds of injection, as hemispheric delta slowing, neuropsychological tests were carried out for localization of memory and language. We were able to lateralize speech and memory dominance in these patients. Peri-procedural complications included transient euphoria (n=1) transient spasm of internal carotid artery (n=1) and generalized tremulousness (n=2). Immediate post procedure there was a drop in blood pressure with average pressure of 116/66 mm of Hg, in all patients, which improved after 30 minutes. Conclusion: We found that PF is well tolerable for the WADA procedure, with no significant complications, although blood pressure should be closely monitored
p729 NEUROLOGICAL AND PSYCHIATRIC ANALYSIS OF ICTAL KISSING AUTOMATISM E. Taskiran*, C. zkara, O. Klc, I. Aydogdu, A. Senturk, and M. Ozmen *Istanbul University Experimental Medicine Research Institute, Istanbul, Turkey; Istanbul University Cerrahpasa Medical Faculty, Istanbul, Turkey; and Ege University, Izmir, Turkey
Purpose: Automatisms are repetative motor activities that occur during or after a seizure followed by amnesia. Several different automatisms have been described which may show complex or simple characteristics where ictal kissing automatism (IKA) is a very rare phenomena. We aimed to study this complex ictal behaviour from neurological and psychiatric aspects in our patients and discuss including the previously reported cases. Method: IKA was determined in four of our patients (3 female, 1 male) during video-EEG monitorization. Ictal EEG and video types were studied in detail and all patients underwent psychiatric analyses to unveil the probable underlying cause of kissing behaviour. Result: Mean age of patients was 30.5 years (2635 years). Seizures recorded were characterised by mainly ictal speech, kissing and gestural automatisms in all patients. The ladies kissed the persons close to them where the young man blew kisses. Seizures related to non-dominant temporal lobe in three (2 right, 1 left) and dominant temporal (right) in one patient. MRI showed mesial temporal sclerosis in 3 of them where it was normal in one. Psychodynamic analysis revealed intense unfulfilled affective requirements which may determine the seizure semiology and they suffered from depression as well. Conclusion: IK is a complex behaviour which may occur as a result of release phenomena rather than a cortical stimulation related to mainly non dominant temporal lobe and generally in women. Family dynamics, developmental history, personality, life style, feeding and love instincts may all play a role in the emergence of this rare automatism during a seizure.
p731 PERCEPTIONS OF STRESS IN LEFT TEMPORAL LOBE EPILEPSY AND DIFFERENCES IN RESPONSE TO ACUTE STRESS J. Allendorfer, H. Heyse, L. Mendoza, and J. Szaflarski University of Cincinnati Academic Health Center, Cincinnati, OH, USA
Purpose: This study examined the effects of acute stress on assessments of mood, anxiety and stress in left temporal lobe epilepsy (LTLE) patients. Method: 23 LTLE patients were included; 16 believed that stress affected their seizure control (LTLE+S) while 7 did not (LTLES). Also included were 17 neurologically healthy controls, stratified as high-stress (HC+S; n=9) or low-stress (HCS; n=8). Subjects participated in a challenge that induces moderate amounts of stress. Pre-challenge mood and stress/anxiety levels were assessed using the Beck Depression Inventory (BDI-II), Profile of Mood States (POMS), State-Trait Anxiety Inventory (STAI), Positive Affect (PA) and Negative Affect (NA) Schedule (PANAS), Dundee Stress State Questionnaire (DSSQ), and 10-item Perceived Stress Scale (PSS-10). The STAI, PANAS, DSSQ, and PSS-10 were also administered post-challenge. T-tests were performed to examine differences between +S and S groups and assess pre-/post-challenge assessment changes within each of the groups (significance at p<0.05). Result: BDI-II did not differ between +S and S groups. LTLE+S and LTLES did not differ on assessments except POMS vigor-activity subscale (LTLE+S>LTLE-S). Compared to HCS, HC+S scored higher on pre-challenge POMS, PSS-10, STAI, NA and DSSQ distress and lower on PA; differences remained post-challenge except DSSQ distress
213 Abstracts
(p=0.1). LTLE+S showed pre-/post-challenge changes: decreasing PA, increasing NA, decreasing DSSQ engagement, and increasing DSSQ distress. HCs also showed increasing DSSQ distress pre-/post-challenge. Conclusion: Acute psychological stress has greater negative impact on mood and stress-related constructs in LTLE+S patients who believe stress affects seizure control compared to LTLES and HC subjects. ders. Depression was detected in 31 patients (21 female, 10 male) of 140 patients. Thirty-two percent of patients with depression had partial, 68% had generalized seizures. Among patients without psychiatric disorder (60 female, 49 male), 29% had partial, 71% had generalized seizures. There were significant differences in age and the presence of cerebral lesion between patients with depression and patients without psychiatric disorder. The mean age was 4219 years and the rate of cerebral lesions was 42% in patients with depression. The mean age was 3219 years and the rate of cerebral lesions was 22% in patients without psychiatric disorder. There were no significant differences in gender, family history, the history of febrile convulsions, seizure frequency and the type of antiepileptic medication. Conclusion: The psychiatric aspects of epilepsy are affected by many factors, including the epileptogenic location and nature of the underlying lesion. Studies have shown up to a 1160% incidence of depression in epilepsy. Depression ratio was found as 17% in our study. Our results also suggests that the lesion ratio is nearly two-fold higher in patients with depression in epilepsy. Further investigations are needed.
p732 ILLNESS PERCEPTION, QUALITY OF LIFE AND COPING STYLES IN PATIENTS ADMITTED TO AN EPILEPSY MONITORING UNIT J. A. Magee*, E. T. Burke, N. P. Pender*, N. Delanty*, and G. M. Fortune* *Beaumont Hospital, Dublin, Ireland; and University College Dublin, Dublin, Ireland
Purpose: To examine the relationship between illness perception, quality of life and coping styles in a sample of patients admitted to an Epilepsy Monitoring Unit. It was hypothesised that illness perception would mediate levels of distress, coping style and quality of life. Method: This study utilises a double-blind design. Data were collected as part of a larger ongoing prospective study of patients admitted to the Epilepsy Monitoring Unit in Beaumont Hospital. Patients completed a large battery of self-report measures, including the Brief-Illness Perception Questionnaire, Coping Inventory for Stressful Situations, Moriskey Medication Adherence Questionnaire, Beck Anxiety and Depression Inventories and the Quality of Life in Epilepsy-13. Result: In total, data on 65 patients with drug resistant epilepsy are reported. Analysis of preliminary data (N=25) collected so far indicates that illness perception impacts on level of anxiety, coping styles and has a direct and indirect impact on quality of life. A larger regression model will be reported on, controlling for gender, seizure frequency and depression scores in order to gain a fuller understanding of the complex relationship between these variables. Conclusion: Preliminary results indicate that illness perception plays an important mediating role in coping styles, anxiety and quality of life. Further analyses will be conducted to examine the impact of depression scores on illness perception, coping styles and quality of life. These findings have important implications regarding the identification of individual illness perception styles in patients with epilepsy and the impact of this upon patients management of their epilepsy and psychological well-being.
p734 FEAR-SPECIFIC MODULATION OF TACTILE PERCEPTION IS DISRUPTED AFTER AMYGDALA LESIONS C. Bertini*, C. Passamonti, C. Scarpazza*, N. Zamponi, L. Provinciali, and E. Ldavas* *University of Bologna, Cesena, Italy; Ospedali RiunitiAncona, Ancona, Italy; Ospedali Riuniti-Salesi, Ancona, Italy; and Universit Politecnica delle Marche, Ancona, Italy
Purpose: The perception of tactile stimuli on the face is modulated when subjects concurrently observe a face being touched; this effect is termed Visual Remapping of Touch, or the VRT effect, and might represent a visually evoked somatosensory activity. VRT effect is modulated by specific key information processed in face-to-face interactions: facial emotional expression. Indeed, tactile perception in healthy subjects is enhanced when viewing touch towards a fearful face compared to viewing touch towards neutral, happy or angry expressions. The fear-specific modulation of the VRT effect might be interpreted as an adaptive preferential enhancement of the somatosensory cortices in presence of fearful stimuli. The present experiment was designed to test whether the amygdala, a crucial neural site in fear perception, might contribute to this effect. Method: Six epileptic patients (mean age: 20 years) with lesions to the amygdala due to temporal lobe resection received tactile stimuli near the perceptual threshold, either on their right, left or both cheeks. Concurrently, they watched several blocks of movies depicting a face with a neutral, happy or fearful expression that was touched or just approached by human fingers. Participants were asked to distinguish between felt unilateral and bilateral tactile stimulation. Result: Tactile perception was enhanced when viewing touch only towards a neutral face, while no effect was found when patients viewed touch towards fearful or happy faces. Conclusion: Results of the present experiment suggest that the amygdala modulates the activity of the somatosensory cortices, playing a crucial role in mediating the fear-specific enhancement in the VRT effect.
p733 DO BRAIN LESIONS INCREASE THE RISK OF DEPRESSION IN EPILEPSY? N. Cinar, S. Sahin, T. O. Onay, K. Batum, and S. Karsidag Maltepe University, Faculty of Medicine, Istanbul, Turkey
Purpose: Psychiatric disorders are observed more frequently in patients with epilepsy and may cause an important impact on quality of life. In this study, we have investigated the relationship between depression and brain lesions in epileptic patients. Method: Epileptic patients who had complete radiologic and neurophysiological data were enrolled to the study. Epileptic seizures were classified according to the International League Against Epilepsy (ILAE) classification of epileptic seizures (1981) and psychiatric diagnoses were categorized according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). The presence of brain lesions were compared in epileptic patients with or without depression. Result: One hundred eighty epileptic patients were enrolled to the study. Forty patients were excluded who had non-depressive psychiatric disor-
p735 FACIAL IDENTITY AND EMOTION RECOGNITION IN PATIENTS WITH MESIAL TEMPORAL LOBE EPILEPSY A. Gomez-Ibaez*, E. Urrestarazu*, G. Arrondo, M. A. Pastor*, and C. Viteri* *Clinica Universidad de Navarra, Pamplona, Spain; and Center for Applied Medical Research, Pamplona, Spain
214 Abstracts
Purpose: To evaluate facial identity and emotion recognition in patients with mesial temporal lobe epilepsy due to amygdalo-hippocampal sclerosis (MTLE-AHS). Method: We studied patients diagnosed with MTLE-AHS, idiopathic generalized epilepsy (IGE) and healthy controls. Baseline cognitive function was assessed through neuropsychological tests. Identity recognition was evaluated with computerized Benton Facial Recognition Test (BFRT) and recognition of basic emotions (anger, disgust, fear, happiness, sadness and surprise) with Ekman & Friesen test (E&FT). Time gap between presentation of emotion and response was measured. Result: Seven MTLE-AHS, 10 IGE patients and 20 healthy controls were analyzed. Median age was 35.6, 30.7 and 37.9 years respectively. Trail-Making-part B, Digit Span and word fluency tasks were significantly impaired in MTLE-AHS patients (p<0.05). MTLE-AHS patients scored lower than controls in BFRT (36.4 vs 41.9), but slightly higher than IGE individuals (36.4 vs 35.8; n.s.). MTLE-AHS subjects scored lower in E&FT (40.7) than IGE (42.9) and healthy controls (49.5; p<0.05). Happiness was the easiest emotion to recognize; fear the most difficult, especially for MTLE-AHS patients (35.7% of success) vs controls (62.5%). Recognition time was globally longer in wrong than in correct responses (4.7 vs 3 seconds). The longest difference was observed in MTLE-AHS individuals (5.8 vs 3.4 seconds); generally, MTLE-AHS answers delayed more than IGE or healthy subjects. Conclusion: MTLE-AHS patients seem to have a facial emotion recognition impairment, especially fear, with longer response time. Mild difficulty in identity recognition was also pointed. Mechanisms involved in emotion recognition failure could be investigated with other techniques such as fMRI or eye-tracking.
p737 QUANTITATIVE METHOD FOR IDENTIFICATION OF THE LANGUAGE ELOQUENT AREAS DURING PRESURGICAL SEEG RECORDINGS C. Pastori*, V. Gnatkovsky*, S. Francione, F. Pelle, L. Castana, and M. De Curtis* *Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Ospedale Niguarda C Granda, Milan, Italy; and Niguarda General Hospital, Milano, Italy
Purpose: A definition of eloquent areas of the brain in drug resistant epilepsy patients explored by stereo-EEG is fundamental for defining the boundaries of the resection. These patients may present peculiar and subverted anatomy. The development of quantitative method for identifying task-related anatomical areas while performing neuropsychological test during the recording sessions, could help in surgical decision. Method: A new software (Elpho-SEEG) for computerized stereoEEG signals analysis was developed to compare brain activity during neuropsychological tests and control condition. Fluency tasks (phonemic- semantic) were analyzed in 11 right-handed patients explored in dominant frontal lobes. Identified anatomic areas were correlated with electrophysiological stimulation responses during SEEG recordings. A co-localization of activated contacts was performed with MRI data. Result: Different frequencies and the relative power evaluated by Fourier transformation and further integral algorithms were analyzed in all recording leads. Difference in the power of frequencies between control conditions (quiet awake, Benton test) and fluency tasks was identified. In all the cases, frequency changes in brain structures involved in language network was observed. The frequency changes were patient specific and not task or structure specific. These areas often corresponded to structures where electrical stimulations induce language disturbances. Test activated contacts were visualised on MRI. Conclusion: Fluency task frequency changes defined by our quantitative analysis can be used to identify language structures explored by intracranial electrode. Validation of our method on larger group of patients is necessary to apply it in surgical planning, outcome prediction and investigation of other cognitive networks. Supported by Italian Ministry of Health Young Investigator Grant 2007.
p736 NEUROPSYCHOLOGICAL OUTCOMES IN ADULTS WITH TUBEROUS SCLEROSIS COMPLEX A. Vignoli*, K. Turner*, F. La Briola*, A. Piazzini*, E. Zambrelli*, V. Chiesa*, G. Scornavacca*, R. M. Alfano, and M. P. Canevini* *St Paolo Hospital, Milan, Italy; and Department of Molecular Biology, Milan, Italy
Purpose: Tuberous sclerosis complex (TSC) is an autosomal-dominant genetic disorder and is a frequent cause of epilepsy and different degrees of neuropsychological impairements. The goal of this study was to assess cognitive outcome in patients with TSC and identify specific clinical variables correlated to neuropsychological profiles. Method: Out of 119 adult patients currently followed at Neurology IIEpilepsy Center, St Paolo Hospital in Milan, 84 individuals underwent to a complete neuropsychological evaluation. This battery included the following cognitive functions: intelligence, memory, attention, language and executive functions. Subjects were divided into three groups (normal cognition, mild delay, moderate-severe delay) according to results obtained from cognitive evaluation. Result: Of 84 enrolled patients (56 F, 28 M, mean age = 34.0), there were 31 (37%) subjects with normal cognition, 21 (25%) with mild delay and 32 (38%) with moderate-severe delay. 72 subjects (85%) had epilepsy, with mean age at onset of seizures of 3.9 years (ranged from 1 month to 48 years). 33 (46%) had a history of infantile spasms and 34 (47%) presented refractory epilepsy. 17 (20%) patients were diagnosed with TSC1 mutation, 49 (58%) with TSC2, 9 (11%) with no mutation and 9 (11%) are ongoing. Cognitive outcomes were correlated with age of epilepsy onset, history of infantile spasms, genetic analysis, refractory epilepsy and seizure frequency (p<0.05). Conclusion: Our data suggest that, in patients with TSC, the age at onset of epilepsy, history of infantile spams, seizure frequency and genetic mutation are predictive of cognitive function.

p738 LONG-TERM EVOLUTION OF DIFFERENT NEUROPSYCHOLOGICAL PHENOTYPES IN SCN1A SPECTRUM C. Passamonti*, C. Petrelli, L. Provinciali, and N. Zamponi *Ospedali Riuniti-Ancona, Ancona, Italy; Universit Politecnica delle Marche, Ancona, Italy; and Ospedali RiunitiSalesi, Ancona, Italy
Purpose: Mutations of SCN1A-gene cause epilepsy syndromes of variable severity, from familial febrile seizures (FS) to partial Epilepsy with Febrile seizure plus (PEFS+), Generalized Epilepsy with Febrile seizure plus (GEFS+), and finally Dravet Syndrome, along with its mild variant (Catterall et al, 2010). These different clinical phenotypes are characterized by widely variable cognitive and behavioural profiles. The present study was aimed to investigate the long term neuropsychological evolution of epileptic patients carrying a SCN1A-gene mutation. Method: Twenty subjects with recurrent febrile and afebrile seizures in the first two years of life and confirmed SCN1A-gene mutation were
215 Abstracts
studied both prospectively and retrospectively. Clinical data and formal neuropsychological assessments including cognitive level, language, executive functions, visuo-motor functions and behaviour were available since epilepsy onset to the late adolescence. Result: Patients diagnosed as Dravet showed the lowest cognitive level at epilepsy onset and the worst clinical and neuropsychological evolution, especially those who experienced status epilepticus in childhood. Autistic symptoms and hyperactivity were present in most of these patients. Patients with the mild variant showed a borderline cognitive level, a greater impairment in visuo-motor than linguistic functions, and emotional disturbances until adolescence. GEFS+ patients showed normal cognitive functioning but a delay in language acquisition and impairments in visuo-motor functions, which progressively improved after 6 years of age. No cognitive and behavioural problems were detected in PEPS+ patients. Conclusion: SCN1A-gene mutations are associated to different neuropsychological profiles, characterized by language impairments and common difficulties in visuo-motor functions. Clinical variables linked to epilepsy's severity modulate the neuropsychological evolution. Purpose: To compare the screening abilities of montreal cognitve assessment (MoCA) and minimental state examination (MMSE) in detecting cognitive impairments in idiopathic epilepsy patients. Method: Scores on the MoCA and the mini-mental state examination (MMSE) were compared in 100 patients with idiopathic or probable symptomatic epilepsy and 30 age- sex- edu-matched controls. As previously recommended, a MoCA score less than 26 was used to indicate the presence of at least mild cognitive impairment (MCI). Results: Epilepsy patients exhibited significantly decreased MoCA scores compared to controls, whereas MMSE scores showed no difference between two groups. The percentage of epliepsy patients scoring below a cutoff of 26/30 was higher on the MoCA than on the MMSE. 31.03% of patients with normal MMSE scores had cognitive impairment according to their MoCA score. Impairments were seen in several cognitive domains, includingvisuospatial and executive abilities, attention, memory, and language. Conclusion: Compared to MMSE, the MoCA may be a more sensitive tool to identify varies cognitive impairments in epilepsy patients.
p739 STEREOTACTIC RADIOFREQUENCY AMYGDALOHIPPOCAMPECTOMY FOR THE TREATMENT OF TEMPORAL LOBE EPILEPSY: DO GOOD NEUROPSYCHOLOGICAL AND SEIZURE OUTCOMES CORRELATE WITH HIPPOCAMPAL VOLUME REDUCTION? H. Malikova, L. Kramska, R. Liscak, Z. Vojtech, and T. Prochazka Na Homolce Hospital, Prague, Czech Republic
Purpose: Temporal lobe surgery bears the risk of a decline of neuropsychological functions. Stereotactic radiofrequency amygdalohippocampectomy (SAHE) represents an alternative to mesial temporal lobe epilepsy (MTLE) surgery. This study compared neuropsychological results with MRI volumetry of the residual hippocampus. Method: We included 35 patients with drug-resistant MTLE treated by SAHE. MRI volumetry and neuropsychological examinations were performed before and 1 year after SAHE. Each year after SAHE clinical seizure outcome was assessed. Result: One year after SAHE 77% of patients were assessed as Engels Class I, 14% of patients was classified as Engels II and in 9% of patients treatment failed. Two years after SAHE 76% of subjects were classified as Engels Class I, 15% of patients was assessed as Engels II and in 9% of patients treatment failed. The hippocampal volume reduction was 5817% on the left and 5427% on the right side. One year after SAHE the intelligence quotients of treated patients increased. Patients showed slightly significant improvement in verbal memory (p=0.039) and semantic long-term memory subtest (LTM) (p=0.003). Patients treated on the right side improved in verbal memory, delayed recall and LTM. No changes in memory were found in patients treated on the left side. There was a trend between the larger extent of the hippocampus reduction and the improvement in visual memory in speech-side operated (p=0.057). No other relationships between the hippocampal reduction and clinical outcome were significant. Conclusion: SAHE causes partial hippocampal destruction, but seizure outcome is comparable with open surgery and moreover SAHE does not cause neuropsychological deficits.
p741 CHANGES IN NEUROCOGNITION AND QUALITY OF LIFE AFTER BILATERAL ELECTRICAL STIMULATION OF THE ANTERIOR THALAMIC NUCLEI IN 7 PATIENTS WITH REFRACTORY EPILEPSY M. Milian*, I. Wisniewski, A. Wendling, S. Klamer*, A. Gharabaghi*, and S. Rona* *University Hospital Tuebingen, Tbingen, Germany; and Epilepsy Center, Kehl-Kork, Germany
Purpose: The SANTE study reported memory problems and depression as adverse events of deep brain stimulation (DBS) of the anterior thalamic nuclei (ATN). We assessed changes in neurocognition and quality of life (QoL) after bilateral DBS of the ATN in patients with refractory epilepsy. Method: Seven adult epilepsy patients (4 female, 3 male) underwent comprehensive neuropsychological testing and completed QoL and psychiatric inventories before DBS surgery. Three patients were re-evaluated 4 weeks after implantation of electrodes, but before onset of stimulation, all 7 patients after 4 months of stimulation, and one patient after an additional 4 months of unilateral (right) stimulation. Result: One month after implantation, before turning on the stimulator, we observed only a slight decline in verbal long-term memory, but improvement of depression and QoL scores. Four months after stimulation onset we noticed a significant decrease in nonverbal short-term memory and a tendency towards verbal and nonverbal long-term memory decline. There were no changes in general cognitive abilities (IQ), attention, executive and language functions or visuospatial abilities. Mood, QoL and psychiatric profile also remained unchanged. In one patient where left-sided stimulation was turned off due to a decline in verbal memory, we observed a recovery 4 months after deactivation. Conclusion: In the present sample we demonstrated (reversible) verbal and nonverbal memory changes as a medium-term effect of DBS of the ATN in epilepsy patients. Stimulation affected no other cognitive functions, mood, QoL or psychiatric scales. Further investigations are scheduled in a larger group of patients.
p740 MONTREAL COGNITIVE ASSESSMENT PERFORMANCE IN PATIENTS WITH EPILEPSY J. Ding, L. Mao, and X. Wang Zhongshan Hospital, Fudan University, Shanghai, China
p742 ACCELERATED LONG-TERM FORGETTING, SUBJECTIVE MEMORY COMPLAINTS AND DEPRESSION IN MEDIAL TEMPORAL LOBE EPILEPSY S. Yagci*, M. Uzan*, L. Hanoglu, and C. zkara* *Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey; and Istanbul Medipol University, Istanbul, Turkey
216 Abstracts
Purpose: Patients with medial temporal lobe epilepsy (MTLE) often present with memory complaints despite performing within normal limits on standard memory tests over usual delays (30 minutes). More recently MTLE has been associated with the phenomenon of accelerated longterm forgetting (ALF). This study aim to investigate ALF phenomenon and its relationship with subjective memory complaints and depression in MTLE patients. Method: Twenty-six patients with MTLE and 23 healthy controls were given California Verbal Learning Test (CVLT), Subjective Memory Complaints and Beck Depression Inventory. Participants were tested on CVLT for learning, immediate recall and recognition at 30 min, 1 week, 6 week intervals. Accelerated forgetting rate was calculated by decay of recognition scores Result: In contrast to patients with right MTLE and control group, left MTLE patients showed significantly poorer performance on learning trials and greater ALF on 30 minutes recognition. At the first and 6 week recognition, both groups of patients demonstrated close forgetting rates unlike controls. On the measure of accelerated forgetting, both patient group showed significant ALF comparison to control group. Between first and 6 week interval, either right and left MTLE patients demonstrated faster decay of forgetting. Also depression and subjective memory complaints trend towards greater at left MTLE patients but did not differ in right MTLE and controls. Although depression were not found associated with ALF, decay of immediate and 30 minutes recall negatively correlated with depression scores in all groups. Conclusion: The findings provide evidence consistent with the period of consolidation for verbal memory can be disrupted by both left and right MTLE. Patients with left MTLE show slightly significant accelerated long-term fogetting and trend towards greater depression.
p744 APPLICABILITY OF A MEMORY ASSOCIATION TASK FOR FMRI IN EPILEPSY SURGERY N. L. Frankenmolen*, M. Hendriks, H. Bergmann, A. Aldenkamp, P. Hofman, R. Kessels, and P. Ossenblok *Radboud University Nijmegen, Nijmegen, The Netherlands; Epilepsy Centre Kempenhaeghe, Heeze, The Netherlands; Radboud University Nijmegen, Nijmegen, The Netherlands; Kempenhaeghe, Heeze, The Netherlands; and Heeze, The Netherlands
Purpose: Epilepsy patients undergoing neurosurgery are at risk for postoperative language and memory deficits. To minimize this risk it is important to assess brain regions for language and memory preoperatively, using a non-invasive method such as fMRI. For language lateralization this has been successful. However, no sensitive fMRI memory task is currently available for this purpose. The objective of this study is to develop and examine a sensitive fMRI memory task (face-name-association memory) that provokes bilateral hippocampal activation in healthy volunteers. Method: Ten healthy adults participated in the study (6 females, mean age 36.7, sd 18.2). The participants encoded the faces and names in the scanner, while functional images were obtained. A recognition task was performed afterwards. Results from the random effects analyses were first thresholded at p< 0.001 (uncorrected). Subsequently, an anatomical region of interest (ROI) of the hippocampas was used to mask for smallvolume corrections (tested at pFDR < 0.05). Results: Showed significant hippocampal activations in 9 out of 10 participants. The ROI analysis showed bilateral hippocampal activations in 8 participants and unilateral hippocampal activations in one participant. In one participant no task-specific hippocampal activation could be determined. The mean recognition score across all participants was 75% (M=36.3/48, sd=5.6). Conclusion: The present study shows that this face-name-association task is a useful fMRI memory task that provokes bilateral hippocampal activations in individual participants. This may be a suitable task for clinical purposes. Further research will focus on validating this task in the preoperative memory assessment of epilepsy surgery candidates.
p743 NEUROPSYCHOLOGICAL OUTCOME AFTER EPILEPSY SURGERY IN PATIENTS WITH BILATERAL AMMON'S HORN SCLEROSIS V. L. Vogt*, M. P. Malter*, J. Schoene-Bake*, C. G. Bien, M. Von Lehe*, H. Urbach*, J. Witt*, and C. Helmstaedter* *University of Bonn, Bonn, Germany; and Krankenhaus Mara, Bielefeld, Germany
Purpose: To retrospectively evaluate the risks versus benefits of epilepsy surgery in patients with bilateral ammon's horn sclerosis (bAHS) regarding cognition, mood, and quality of life. Method: Neuropsychological outcome of eleven surgically and eight medically treated patients with bAHS was evaluated. Memory (verbal/ figural) and executive functions (fluency, response inhibition) were assessed in terms of individual scores and a composite memory or attention scores. Additionally, mood and quality of life were evaluated. Result: Within the observation interval, 91% of the surgical but no medical patients achieved seizure freedom. Executive functions did not change in either group. Despite severe memory deficits already at baseline, the surgical group significantly declined in the composite memory (z=-2,401, p=.016). Reliable change indices (CI = .90) revealed that while 27% of the surgical group declined in the composite memory score, no patients improved (individual scores: 73% decline and 9% improvement in verbal memory; no change in nonverbal memory). In the control group, no declines of the composite memory score were evident (individual scores: 25% decline in verbal memory, 13% decline in nonverbal memory). At follow up, the groups did neither differ with respect to subjective memory impairment in everyday life nor in regard to mood or quality of life. Conclusion: Our findings suggest that despite undeniable benefits concerning seizure control and very poor memory already at baseline, patients with bAHS still show additional postoperative memory decline. This and the lack of benefits regarding subjective cognition, mood and quality of life put the overall outcome in perspective.
p745 LANGUAGE AFTER TEMPORAL LOBE EPILEPSY SURGERY A. R. Giovagnoli, V. Manfredi, A. Parente, S. Oliveri, G. Didato, F. Deleo, L. DIncerti, C. Marras, F. Villani, and R. Spreafico Fondazione IRCCS Istituto Neurologico C. Besta, Milano, Italy
Purpose: Language competence depend on the integrity of different neural networks including the inferior-lateral temporal, superior parietal and frontal cortices, and the ventral visual pathway or the inferior frontal, dorsolateral prefrontal, medial temporal and parietal areas. Although many studies investigated language after epilepsy surgery, scarce attention was given to the postoperative trajectories of different lexical-semantic abilities. This prospective study evaluated the short and long-term changes of word finding on visual, letter, and category stimuli in patients operated on for drug-resistant temporal lobe epilepsy (TLE). Method: Eighty-eight adult patients with left or right TLE were evaluated before and six months and one, two, three, and four years after surgery. The surgical resections involved, to different extent, the anterior lateral and medial temporal lobe structures. The Boston Naming and Word Fluency tests on phonemic and semantic cues were used to assess word finding on visual (line-drawing) stimuli, search by letter, or category access to the lexical store.
217 Abstracts
Result: All patients reported complete seizure remission except for 14 cases with sporadic attacks. With respect to the preoperative evaluation, at the 6-month follow-up, the naming test scores were significantly lower in the left TLE patients and higher in the right TLE patients, but, at the 1year, 2-year, 3-year and 4-year follow-ups, naming improved in both groups. In left and right TLE, word fluency on phonemic or semantic cues progressively increased after surgery. Conclusion: Word-finding abilities tend to improve 14 years after left or right TLE surgery, showing different trajectories. Early impairment and subsequent improvement of picture naming strictly relate to left TLE, whereas word finding by letter or category improves irrespectively from the side of surgery. These results indicate that, in selected patients, language can continue to ameliorate for long time after surgery. Ongoing liberation of anterior and posterior cortical areas from the interference of epileptic discharges may explain language recovery. tics. The Delayed Matching to Sample (DMS-48) task was previously shown to successfully assess visual recognition memory deficits in early Alzheimer Disease, thus we determined that this task was applicable for lateralisation of hippocampal regions and parallel versions for evaluation of postoperative memory outcome. Method: Forty-eight preoperative mesial temporal lobe epilepsy (TLE) patients were given a full neuropsychological battery containing a variety of standard verbal and figural learning and reproduction memory tests, in addition to the DMS-48. Furthermore, to eliminate practice effects post-operatively, two parallel versions of the DMS-48 were developed and normalised in 172 healthy controls. Using these parallel versions allowed a group of TLE patients to be assessed postoperatively. Result: Our analysis revealed highly significant differences between the left and right mesial temporal lobe for both the DMS-48 and the parallel versions, but not for any of the other visual memory tasks we studied. The two parallel versions administered to the control group were found to be comparable tools to the original task, and could thus be utilized for the postoperative follow up. Postoperatively, all visual memory measures remained stable, while performance on verbal memory tasks diminished in the left TLE patients. Conclusion: The present findings suggest that clinical usefulness is high for both the DMS-48 and its parallel versions for pre- and postsurgical cognitive epilepsy evaluation, by lateralising the ictal onset zone and controlling postoperative changes.
p746 TEMPORAL LOBE EPILEPSY IMPAIRS ADVANCED COGNITIVE ESTIMATION ABILITIES A. Parente*, A. Tarallo*, F. Villani, R. Spreafico, and A. R. Giovagnoli* *Fondazione IRCCS Istituto Neurologico C. Besta, Milano, Italy; and Fondazione IRCCS Istituto C. Besta, Milano, Milano
Purpose: Cognitive estimation, an ability to attribute measurements to concrete things, stands on individual semantic knowledge and experiences, contributing to everyday decision making and behaviour. Temporal lobe epilepsy (TLE) is a well-known cause of memory deficits but other cognitive impairments may be observed in patients with medically intractable seizures, playing an important role in localizing the epilepsy related dysfunction. The aim of this study was to determine cognitive estimation deficits in TLE patients, candidates to epilepsy surgery. Method: One hundred and eight e TLE patients and 51 healthy subjects were evaluated. The Cognitive Estimation Task (CET) requiring simple and complex estimations and tests assessing executive, attentive, perceptual, praxis, language, and memory functions were used. Result: Both left and right TLE patients showed significantly lower CET scores than controls. In the whole patient group, the CET scores correlated with executive and language test scores, the age at seizure onset, and epilepsy duration. Conclusion: TLE impairs cognitive estimation, which may reflect the severity of disease and the involvement of other cognitive abilities. Such impairment may depend on damage to the temporal lobes. Alternatively, through pre-existing neuron pathways, long-lasting TLE may interfere with functions supported by distant brain areas that play a role in control functions (e.g., the frontal lobes). As an important cognitive dimension, cognitive estimation deserves attention in drug-resistant TLE patients. Further studies in larger patient populations are needed to confirm these exploratory findings, while longitudinal postoperative studies could help clarify the physiopathological mechanisms of cognitive estimation.

p748 EPILEPSY CHILDREN SUPPORT CAMP L. Cvitanovic-Sojat, B. Divcic, R. Gjergja Juraski, M. Malenica, M. Kukuruzovic, N. Rajacic, and N. Krmek UHC Sestre milosrdnice, Zagreb, Croatia
Purpose: To analyze the benefits of a week long summer camp organized by the Croatian Biro for Epilepsy and supported by the City Office of Zagreb for Health and War Veterans. Method: A summer camp was established for children with epilepsy of normal intellect and with well-controlled seizures on anti-epileptic medication. Camp staff included doctors, psychologist, nurses and trained volunteers. Activities included swimming, group sports, arts and crafts, wildlife exploration and entertainment. Eight education sessions were provided by psychologists/neuropaediatricians and were centered on improving knowledge of seizures, the importance of medication and on managing lifestyle issues such as employment and driving. Discussion with camp participants occurred in groups or in one-on-one sessions. The impact of the educational sessions was evaluated at the beginning and at the end of the camp. Questionnaires explored stressors and methods of relaxation, bullying, concentration, knowledge about epilepsy and satisfaction with the camp. Result: A total of 20 children attended the camp, (males =10, age range 8 to 18 years, mean age 13 years and 11 months). The analyses showed that 15/20 children were aware that they had a diagnosis of epilepsy, but that none knew what epilepsy was. Only parents knew the diagnosis in 2/ 20. One child had a generalized seizure and one child had an absence seizure during the camp. Conclusion: All participants were encouraged to reach their full potential in life and to improve their knowledge of epilepsy and associated lifestyle modifications to ensure good health. Participants enjoyed the experience and received education in a supportive environment.
p747 THE DMS-48 AS A VISUAL RECOGNITION MEMORY TASK FOR COGNITIVE EPILEPSY EVALUATION I. Wisniewski*, A. Wendling*, C. Westermann*, L. Manning, and B. J. Steinhoff* *Kork Epilepsy Centre, Kork, Germany; and Laboratory of Imaging and Cognitive Neurosciences (CNRS, UMR 7237, IFR 037), Strasbourg, France
Purpose: Currently no consensus exists regarding the lateralizing validity of established visual memory tests in pre-surgical epilepsy diagnos-
218 Abstracts
p749 INFLAMMATORY TEMPORAL LOBE EPILEPSY: FOCAL RASMUSSEN ENCEPHALITIS? L. De Palma*, C. Sabourdy, L. Minotti, S. Chabardes, and P. Kahane *Neurology Department, University Hospital, Grenoble, France, Grenoble, France; and Grenoble University Hospital, Grenoble, France
Purpose: Rasmussen encephalitis is a well-known form of focal epilepsy associated with brain unilateral atrophy and hemiparesis. It is postulated that some patients, more often adults, could present, at the beginning, a more focal disease that involves later the entire hemisphere. It is still unclear if focal forms of Rasmussen encephalitis do exist. Method: We report the case of a twelve years old girl with normal development who started her epilepsy at the age of 10 years. The seizures were, from the beginning, very frequent and stereotyped. They were characterised by an abdominal aura (painful), followed by gustatory and olfactory hallucinations, with inconstant dizziness. The girl didn't have any speech and consciousness impairment. Inter-ictal and ictal EEG abnormalities were localised on the anterior temporobasal region. MRI showed an ill-defined lesion of the amygdala, hyperintense in T2, hypointense in T1, visible in diffusion. CSF analysis was normal, with no antiNMDA and anti-VGKC antibody. The epilepsy was drug resistant from the onset, with clear anatomo-electro-clinical correlations. Result: A temporo-polar resection including the hippocampus was then performed without neither memory nor speech deficit after surgery. The patient, 10 months after the intervention, is in Engel class 1a. Neuropathological examination showed a perivascular inflammation mainly of type T lymphocyte (CD8/CD4 >1) in the amygdale, without any structural alterations, suggesting a focal form of Rasmussen encephalitis. No additional treatment was proposed. Conclusion: This report enlarges the spectrum of clinical manifestations of Rasmussen encephalitis where very focal forms seem to exist, even in children. Youden's Index a summary measure of sensitivity and specificity - 0.95 (0.930.99). Surveying only parents improved specificity slightly without affecting sensitivity. Repeat survey (n=62) demonstrated 100% concordance. Conclusion: Although numbers are relatively small, early results suggest that AQ may be a more effective population-screening instrument than WQ. In addition, it should greatly improve efficiency as it can readily access individuals and households through devices that access the internet, rather than door-to-door.
p751 THE INFLUENCE OF ANTIEPILEPTIC DRUG THERAPY ON BONE MINERAL DENSITY AND SERUM TOTAL AND IONIZED CALCIUM LEVELS IN CHILDREN AND ADOLESCENTS M. D. Dimic*, and N. A. Dimic *Clinical Center Ni, Serbia, Nis, Serbia; and Institut Niska Banja, Niska Banja, Serbia
Purpose: Longterm use of antiepileptic drugs (AED) in patients with epilepsy can produce a reductions of bone mineral density (BMD). The aim of this study is to evaluate the influence of antiepileptic drugs on bone and calcium metabolism in children and adolescents with epilepsy. Method: We prospectively measured the spinal BMD by dual-energy H-ray absorptiometry and serum total and ionized calcium values in 31 male patients aged 618 years who received AED mono and polytherapy. Result: Despite of BMD apsolute values in lumbar spine region (L1-L4) were significantly decreased (0.8300.14 g/cm2 vs. 0.9080.18 g/cm2; p<0.05), BMD Z-scores (-0.181.47 vs. 0.230.68; n.s.) were not significantly lower in epilepsy patients group compared with control. The serum total and ionized calcium values were significantly lower in male patients with epilepsy compared to control (total calcium levels: 2.300.18 mmol/L vs. 2.450.13 mmol/L p<0.001 and ionized calcium levels 1.150.14 mmol/L vs. 1.230.05 mmol/L p<0.005). Conclusion: Because longterm AED-therapy can produce disturbances in bone mineral metabolism in children and adolescents with epilepsy, both management and calcium and vitamin-D suplementation are necessary.
p750 A NOVEL INTERNET ANIMATION SEIZURE SURVEY MAY BE AN EFFECTIVE SCREENING INSTRUMENT FOR POPULATION-BASED RESEARCH W. J. DSouza, J. Freeman, S. Harvey, and M. Cook The University of Melbourne, Melbourne, Vic., Australia
Purpose: The conventional research method to screen for epilepsy is with a written questionnaire administered door-to-door (WQ). Although this enables comprehensive capture of undiagnosed and untreated cases, it is resource intense, insensitive to non-convulsive seizures and inefficient for large-scale recruitment for aetiologic or prognostic studies. Our aim was to field test a novel digital animation seizure-screening questionnaire that may be more suitable for community-based recruitment. Method: We developed a series of high-resolution digital animations depicting visual sequences of young people with seizures (AQ) consisting of: tonic-clonic, simple partial motor, complex partial temporal lobe, absence and myoclonic. We administered AQ to parents of primary and secondary school students and secondary school students by a specially constructed website www.sparks.org.au. All students underwent epilepsy specialist assessment (ESA) including EEG when indicated, to confirm the diagnosis. AQ was repeated after first completion, to estimate repeatability. Result: 206 AQ internet surveys were conducted (157 parental, 38 students with all undergoing ESA: 8 screened positive with 3 confirmed epileptic seizures, 2 of which were new. Both parental and student's surveys combined: sensitivity 1.00 (1.001.00), specificity 0.95 (0.920.99),
p752 IMPORTANCE OF SUBTLE CLINICAL FEATURES ASSOCIATED TO THE MOTOR PHENOMENON OF EPILEPTIC SPASMS FOR DIFFERENTIAL DIAGNOSIS M. Eisermann*, P. Plouin*, O. Dulac, R. Nabbout, and A. Kaminska *Necker Enfants Malades Hospital, Paris, France; and Hopital Necker Enfants Malades, Paris, France
Purpose: Epileptic spasms are a peculiar seizure type occurring throughout life, in the neonatal period in Othahara syndrome, in infancy in West syndrome, in childhood in late onset epileptic spasms and possibly in Lennox Gastaut syndrome, and in later life in focal symptomatic epilepsies due to focal cortical malformations. The typical clinical manifestation consists in a sudden motor phenomena, longer compared to a myoclonus but shorter compared to a tonic seizure, of variable character and localisation, possibly asymmetrical and/or asynchronous, and most often occurring in clusters. Associated features may occur but can be very subtle and therefore easily be overlooked, but their detection can be very important in the work-up of the underlying etiology. Method: We present the ictal video-EEG recordings and clinical data of patients with epileptic spasms showing a variety of associated features
219 Abstracts
beside the motor phenomenon, as behavioral arrest, decreased responsiveness, chewing, different ocular phenomena and autonomic changes as larming, vomiting, and short lasting cardiac rhythm changes. Result: We present the ictal video-EEG recordings and clinical data of patients with epileptic spasms showing a variety of associated features beside the motor phenomenon, as behavioral arrest, decreased responsiveness, chewing, different ocular phenomena and autonomic changes as larming, vomiting, and short lasting cardiac rhythm changes. Conclusion: Detection and characterization of subtle clinical features associated to the motor phenomenon of epileptic spasms are important to guide the differential diagnosis. Purpose: Cognitive alterations have been associated to benign focal epilepsy of childhood with centrotemporal spikes (BECTS) including the executive functions. We studied the performance of children with BECTS in attention and executive functions tests. All children were within the normal QI. Method: Fifty eight children with ages ranging from 8 to 13 years old were evaluated, 30 with BECTS and 28 control group. Battery test applied: Cubes, Vocabulary, Digits, and Code subtests of the Wechsler Intelligence Scale for children, Stroop test Victoria version, Wisconsin Card Sorting test, Phonemic Verbal Fluency (FAS), Trails test, Concentrated Attention test and Tower of London. Result: Children with left discharges and taking medication presented the performance lower in estimation of QI when compared to the control group, right or bilateral discharge and without medication. The execution time in card one of the Stroop test was higher in the study-group relative to control and showed no significant difference regarding laterality of the discharge and medication. Children with BECTS showed lower efficiency in FAS. Children with left discharge and without medication showed lower results. Relative to the Wisconsin Card Sorting test showed worse performances in the group with left discharge and the group without medication. Conclusion: Children with BECTS showed lower results than the control-group: verbal fluency and solving problems. Children with BECTS present limitations concerning cognition: some aspects of executive function dependent of the discharge and the medication
p753 SCHOOL YEARS FOR CHILDREN WITH EPILEPSY IN GREECE: A VOICE COMING FROM PARENTS AND CHILDREN M. Kampra*, A. Siatouni, A. Verentzioti, N. Tzerakis, G. Androutsos*, E. Katsarou, and S. Gatzonis *Medical School of Athens, Athens, Greece; Athens Medical School, Athens, Greece; University Hospital of North Staffordshire, Staffordshire, UK; and Pegional General Children's Hospital Aglaia Kyriakou, Athens, Greece
Purpose: An effort to understand the school life of children suffering from epilepsy, in Greece from the children's /parent's point of view. Method: After appropriate consent, we interviewed 100 people, with open ended questionnaires, from 10th October 2011 to 10th January 2012, in two hospitals of Athens: Evangelismos (20 adults aged 1945) and Children's Resional General Hospital Panayotis & Aglaia Kyriakou (40 children and 40 parents). 38 parents, 34 children and 18 adults agreed to participate. Result: 76.31% parents had never informed their children about their disease, either because they thought their children were too young to know about their situation or because they were scared of the possible social consequences. They were worried that their children might be targeted if they openly discussed about epilepsy in school. There were concerns about bullying, exclusion from parties and games etc. However, all parents admitted that after being informed about epilepsy, they understood that it is nothing more than a disease. 17.65% children and 44.44% adults had no hesitation talking about their illness to the other pupils at school whereas 62.5%parents, 58.82% children and 55.56 adults said they prefer to keep the illness a secret. All the interviewees addressed the lack of information about epilepsy. Conclusion: Even nowadays epilepsy is a cause of anxiety to the patients, their families and social environment, including school, teachers and training staff. It seems crucial to improve the information about epilepsy, enhance people's understanding about this disease and generate a happier school life for children, parents and teachers.
p755 AN ONGOING EUROPEAN NON-INTERVENTIONAL REGISTRY STUDY OF PATIENTS WITH LENNOX-GASTAUT SYNDROME: INTERIM ANALYSIS M. Nikanorova*, and I. Chouette *Danish Epilepsy Centre, Dianalund, Denmark; and Eisai Europe Limited, Hatfield, UK
Purpose: Rufinamide is licensed in Europe for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients aged 4 years. A non-interventional European registry study is ongoing, to provide long-term data (3 years) on >100 LGS patients initiating rufinamide as add-on therapy and up to 125 LGS patients receiving other antiepileptic drugs (AEDs). Here we present an interim analysis. Method: The registry is enrolling LGS patients (age 4 years) requiring modification to any AED treatment, including initiation of rufinamide. Its primary objective is to evaluate long-term safety. Effects of treatment on seizure control and healthcare resource utilisation are also being assessed. Eighty-one patients from 64 sites in 9 countries are currently enrolled. An interim analysis of the first 60 patients (37 male, 23 female) is presented; 47 having received rufinamide. Result: At baseline, mean (standard deviation [SD]) age was 15.6 (10.4) years; mean (SD) time since LGS diagnosis was 6.1 (8.5) years; and mean (SD) number of prior AEDs was 7.3 (3.8). To date, 47/60 (78.3%) patients have been followed up for 1 year. Median (range) follow-up duration is 24.4 (3.3-40.1) and 27.7 (17.9-32.3) months for patients treated with rufinamide and other AEDs, respectively. AED-related adverse events have been reported by 25.5% and 38.5% patients treated with rufinamide and other AEDs, respectively. One patient (in other AEDs group) has withdrawn due to an AEDrelated adverse event. No unexpected safety findings have emerged to date. Conclusion: The registry is providing useful information on LGS and its management. Supported by Eisai
p754 STUDY OF THE EXECUTIVE FUNCTION IN CHILDREN WITH BENIGN FOCAL EPILEPSY WITH CENTROTEMPORAL SPIKES M. L. G. Manreza, N. Banaskiwitz, C. S. M. G. Miziara, A. P. Valadares, and E. Amaro Hospital das Clnicas of Medicine University os So Paulo, Sao Paulo, SP, Brazil
220 Abstracts
p756 LONG TERM EFFICACY AND HOSPITALIZATION RATE IN CHILDREN WITH REFRACTORY FOCAL EPILEPSY TREATED BY VAGUS NERVE STIMULATION M. Ryz*, R. Kuba, Z. Novk, H. Oslejskova*, M. Brzdil, and I. Rektor *Epilepsy Center Brno, Brno University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic; and Epilepsy Center Brno, St. Anne's University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic
Purpose: The aim of the study is evaluation of long-term efficacy and hospitalization rate in children with refractory focal epilepsy treated by vagus nerve stimulation. Method: We retrospectively analyzed 15 children with intractable focal epilepsy treated by vagus nerve stimulation. We analyzed the effectiveness at 1, 2 and 5 years follow-up. We counted the average number of urgent hospitalizations and number of days of urgent hospitalization per year for each patient before and after the VNS implantation. Result: The mean seizure reduction was 42.5% at 1, 54.9% at 2 and 58.3% at 5 years. The number of responders was 7 (46.7%) at 1 and 9 (60%) at both 2 and 5 years (p<0.001 - in comparison to preoperative period). The mean of number of urgent hospitalization per one patient was 1.00.6 per year preoperatively and 0.30.5 per year postoperatively (p<0.0001). The mean of number of days of urgent hospitalization per one patient was 9.36.1 per year preoperatively and 1.31.8 per year postoperatively (p<0.0001). Conclusion: Vagus nerve stimulation is an effective method in treating children with refractory focal epilepsy. It leads to substantial decrease of number of urgent hospitalizations and the reduction of its duration. Conclusion: The co-existence of SFE plus BFEDC and/or Benign Focal Epilepsy of Childhood should be included early in considerations in children with discordant findings between MRI and EEG. The correct diagnosis can be difficult particularly in cases with atypical BFEDC in addition to an epileptogenic lesion. Recognition of such constellation may have consequences for the choice of drugs and for the timing of presurgical evaluation.
Semiology, Aetiology and Classification 25 Wednesday, 03 October 2012

p758 DRAVET SYNDROME AND OTHER GENETIC AND STRUCTURAL CAUSES OF POST-VACCINATION EPILEPSY: A NATION-WIDE 10-YEAR COHORT STUDY N. E. Verbeek1, F. E. Jansen2, M. J. A. Van Kempen1, D. Lindhout1, N. A. T. Van Der Maas3, and E. H. Brilstra1 *University Medical Centre Utrecht, Utrecht, The Netherlands; Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands; and RIVM, Bilthoven, The Netherlands
Purpose: Dravet syndrome is increasingly recognised as a genetic cause of alleged vaccination encephalopathy. However, little is known on the prevalence and underlying causes of post-vaccination epilepsy in general, and this information may have great impact on public acceptance of vaccination programs. We investigated the outcome and aetiology of epilepsy following vaccination, in a national cohort. Method: The medical data of all 1,269 children with seizures following vaccination in the first two years of life, reported to the National Institute for Public Health and Environment in the Netherlands in 19972006, were systematically reviewed. Of children with onset of epilepsy within 24 hours after administration of an inactivated vaccine, or 512 days after an attenuated vaccine, follow-up data were obtained. Result: Follow-up (median age 10 years) was available for 23 of 26 children with epilepsy onset after vaccination. 11 children had developed epileptic encephalopathies, 4 children had encephalopathy predating the onset of epilepsy, and 8 children had normal cognitive outcomes. Genetic causes were detected in 11 children: nine SCN1A-mutations (eight Dravet, one GEFS+ syndrome), one PCDH19-mutation (EFMR) and one submicroscopic 1qter deletion. Genetic causes were presumed to be present, but were not identified in four children with either neuronal migration disorders or familial epilepsies. Conclusion: In the majority of cases with post-vaccination epilepsy, genetic causes can be assessed (65%). Our study shows that normal cognitive outcome after post-vaccination epilepsy is also common (35%), but confirms that Dravet syndrome is the major cause of cases with postvaccination encephalopathy (73%).
p757 DIAGNOSTIC CHALLENGES IN A PATIENT WITH FOCAL CORTICAL DYSPLASIA TYPE IIB AND BENIGN FOCAL EPILEPTIFORM DISCHARGES OF CHILDHOOD (BFEDC) IN ADDITION , T. Pieper, V. Ivanovic , P. Gr d N. Bariic an, B. Bunoza, I. Lehman, and H. Holthausen University Medical Centre Zagreb, Zagreb, Croatia
Purpose: Discordant findings in children with structural focal lesions like FCD are not so rare, e.g. generalized epileptiform discharges (ED), ED distant from the lesion site or over the hemisphere contralateral to the lesion. Considerations in such situations include further epileptogenic lesions not visible on MRI, irritative spikes because of seizure spread, and idiopathic types of epilepsies in addition. Method: Patient M.D. presented with non localizing/non lateralizing seizures at age of 3.EEG showed ED left centro-temporo-parietal. MRI raised the suspicion of a FCD left fronto-central. Repeated EEGs revealed ED over changing localizations like left and right temporo-parietal, right frontal and left fronto-central (including polyspikes left frontocentral). Seizures were drug resistant and several hospitalizations were necessary because of status epilepticus. A very high resolution MRI during presurgical evaluation confirmed a bottom of sulcus dysplasia left fronto-central. The patient became seizure free after invasive recording with subdural grids and subsequent surgery. Pathology confirmed FCD type IIb. Result: EEGs at age of 14, 6 months post surgery, showed BFEDC right frontal and bi-occipital. Wake- and sleep-EEG normalized at age of 15. The boy is now off drugs and his school performance is excellent.
p759 EPILEPSY IN CHILDREN WITH CEREBRAL PALSY O. Jotovska Institute for Mental Health of Children and Youth, Skopje, Macedonia
Purpose: To present the frequency of epilepsy in children with C.P, epilepsy in different types of C.P. and the importance of the degree of mental retardation in frequency and severity of epilepsy.
221 Abstracts
Method: Files of 100 children are analyzed, age, sex, type of C.P., frequency and degree of mental retardation and number of children with epilepsy. Diagnostic procedures: brain ultrasound, CT and MNRI, EEGs, psychological testing were performed. Result: 11 children of 100 with C.P. suffered from spastic quadriplegia, 25 with spastic diplegia, 16 with spastic hemiplegia, 20 with hypotonic form of C.P., 12 with dyskinetic form and 16 with combinations of the forms mentioned above; 22 children suffer from epilepsy, 35 isolated or combined anatomo-morphologic anomalies were described with the help of imaging methods; EEG was not recorded in 8 children with C.P. The children with epilepsy have epileptiform changes in their EEGs, 7 children did not present any epileptiform changes, 6 children presented nonspecific changes, 31 children with focal changes, 26 with bilateral changes and paroxysms. Concerning mental retardation, borderline intellectual functioning was observed in 5 children, mild mental retardation in 13 children, moderate mental retardation in 6 children, severe mental retardation in 9 children, disharmonic development in 6 children, delay in speech and psychomotor development in 38 children, normal development in 25 children. Conclusion: Children with C.P. exhibit diverse spectrum of co-morbid disorders such as epilepsy. The degree of mental retardation and neurological deficit, especially spasticity has a positive correlation with the frequency and severity of epilepsy.
p761 CLINICAL AND EEG CHARACTERISTICS OF EPILEPSY IN PATIENTS WITH NEURONAL CEROID LIPOFUSCINOSIS R. Kravljanac*, J. Staropoli, K. Sims, N. J. Jovic, and M. Djuric* *Faculty of Medicine, Institute for Mother and Child Healthcare of Serbia, University of Belgrade, Serbia of Serbia, Belgrade, Serbia; Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA; and Department for Neurology and Psychiatry for Children and Youth, Medical School, Belgrade, Belgrade, Serbia
Purpose: Evaluation of clinical and EEG characteristics of epilepsy in children with neuronal ceroid lipofuscinosis (NCL) in the West Balkan region. Method: The study included NCL patients diagnosed by enzyme, genetic, and histopathologic analysis in the period 19912011. The epilepsy presentation, EEG findings and response to AEDs were evaluated. Result: 17 patients (14 males, 3 females) were included: 16 with LINCL (12 with classical type, 4 variant) and one with JNCL. Seizures were the initial manifestations at mean age of 2.8 years in all cases with CLN2, mainly preceded by hyperactivity. Ataxia and mental regression existed before epilepsy in the boy with CLN3 and two siblings with the Finnish variant of LINCL (CLN5). All patients suffered different types of seizures: complex and simple focal with/without secondary generalization, myoclonus; five experienced status epilepticus and three epilepsia partialis continua. Polytherapy was required in 14 cases, often with side effects. EEG showed occipital discharges during slow-frequency photostimulation suggesting diagnosis at early stage in four LINCL cases. Slowing and amplitude decreasing of background activity was obvious with disease progression. Conclusion: LINCL is the most frequent NCL type in the region. Seizures were the initial manifestations in all LINCL cases and were followed by poor controlled epilepsy with variation in clinical presentation of epilepsy, even among the children with the same NCL type Particular EEG features are suggestible for diagnosis. Treatment of epilepsy in NCL patients is challengeable.
p760 RESPONSE TO INTRAVENOUS IMMUNOGLOBULINS IN MALIGNANT MIGRATING PARTIAL SEIZURES IN INFANCY: ONE CASE REPORT P. Morillo*, R. Buenache, K. Escajadillo, C. Mondragn, A. Pedrera, and G. Lorenzo *Ramon y Cajal University Hospital, Madrid, Spain; Hospital Ramon y Cajal., Madrid, Spain; and Ramn y Cajal University Hospital, Madrid, Spain
Purpose: To present one patient diagnosed with malignant migrating partial seizures in infancy (MMPEI) with successful response to immunomodulatory treatment. Method: We report a 19-month-old boy, without relevant medical history, who debuted at 5 and 6 months of age with atypical febrile seizures. Neurological examination and complementary tests (CSF, EEG, CT and brain MRI) were normal, being treated with valproate. Result: From 7 months of age, the patient had recurrent episodes of polymorphic seizures with loss of consciousness, irritability, hypotonia, autonomic and left or right focal motor symptoms, as status epilepticus, in relation with febrile and afebrile infectious processes. We observed a stop in his neurocognitive development and an autism-like behaviour. Sequential EEGs (awake and asleep) showed recurring seizures of both brain hemispheres. The neurometabolic study (blood / CSF), antineuronal antibodies, molecular analysis of gene SCN1A and GABRG2, were normal. The patient was treated with a combination of levetiracetam, pyridoxine, ACTH / corticosteroids, lacosamide and ketogenic diet, with no clinical response so, iv gammaglobulins (IGIV) was associated (2 g/kg). At 12 months of age he had severe primary hypertriglyceridemia and hypercholesterolemia, requiring urgent plasmapheresis and stopping ketogenic diet. At present background medications include valproate, levetiracetam, lacosamide and IVIG, observing an improvement in neurological state, disappearance of paroxysmal EEG abnormalities and lack of seizures in the last 7 months. Conclusion: We identified seizure control in a patient with refractory MMPEI after treatment with IVIG. We cannot rule out that he is in a seizure-free period due to the natural outcome of the disease.
p762 BEHAVIOURAL PROBLEMS AND EEG CHARACTERISTICS OF CHILDREN WITH BENIGN CHILDHOOD EPILEPSY WITH CENTROTEMPORAL SPIKES R. Samaitiene Vilnius University, Lithuania
Purpose: 1) To investigate the behavioural problems in children with benign childhood epilepsy with centrotemporal spikes (BECTS), to compare with data of patients with peripheral nervous system disorders (PNSD); 2) To estimate the relationship of age when first seizure occurred, duration of epilepsy and treatment, EEG spiking parameters, schooling data and behavioural problems. Method: 23 patients with BECTS, 20 patients with peripheral nervous system disorders, aged 611 years, equally distributed for age and gender attending regular schools were investigated. Evaluation was made using the Lithuanian version of Child Behaviour Checklist (CBCL). Result: Children with BECTS had significantly higher scores in Anxious/Depressed (5.02.9 vs 4.02.7, p=0.004), Social Problems (3.93.2 vs 3.12.3, p=0.017), Attention Problems (5.73.0 vs 4.33.1, p=0.002) and Aggressive Behaviour (6.84.6 vs 5.34.0, p=0.003) subscales, compared with the patients with PNSD. There were significant relationships established in the BECTS patients group: 1) the higher were scores of
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Attention Problems subcale, the lower were grades native language (r= 0.560, p=0.03); 2) the longer was the treatment, the lower were grades mathematics (r=-0.581, p=0.023); 3) the earlier was the beginning of seizures, the greater were the results of Delinquent Behaviour scores (r=0.308, p=0.047). Presence of additional extrarolandic focus and focal specific discharges spreading to centrofrontotemporal, centroparietotemporal areas were related to higher scores of Social Problems, Attention Problems and Delinquent Behaviour (r=0.421, p=0.018; r=0.543, p=0.002; r=0.361, p=0.04) in the BECTS patients group. Conclusion: Children with BECTS are at risk for behavioural problems. Presence of discharge location other than centrotemporal was related to higher scores of behavioural problems. struct context, mechanism and outcome chains to understand why particular models of service delivery work during transition, for whom and under what circumstances. Result: Joint epilepsy clinic facilitated by paediatrician, adult neurologist and supported by an epilepsy nurse was found to be most effective. Continuity of care at staged intervals enabled young people to engage with adult healthcare professionals once transitioned to adult services. Age-appropriate information improved self-management skills by young people whereas information lacking clarity caused psychological problems. Majority of young people had difficulty remembering information. Psychological care was inadequate. Majority of parents lacked basic information to encourage their child to safe self-care. Translation of policies and guidelines into clinical practice was weak. Conclusion: This study makes significant contribution to understanding to what constitutes good communication and good transition from the perspective of young people with epilepsy and their parents.
p763 YIELD OF BRAIN IMAGING OF CHILDREN WITH SEIZURE FOLLOWING REFERRAL S. Al-Ani, and A. Mas Queen's University Hospital, London, UK
Purpose: To examine the yield of brain imaging among children and adolescents with seizure Method: Rterospective analysis of prospectively collected data. 361 Patients were categoriesed into two groups. Group I consisted of 245 patients with normal neurological examination and normal neurodevelopment. Group II consisted of patients (n=116) with abnormal neurological signs and or sepcific learning difficulties / global neurodevelopment delay. Idiopathic epilepsy was defined as only epilepsy. Brain abnormalities were considered non-significant if they were non-specific findings and ulikely to cause seizure. Result: Significant brain abnormalities were found in 49/361 (13.6%) patients. Of these, 16 patients (6.5%) were in group I and 33 (28.5%) patients were in group II. Conclusion: Brain imaging should be considered for patients with seizures, normal neurological examination and normal neurodevelopment.
p765 A PILOT STUDY INVESTIGATING THE EFFECT OF CHILDHOOD EPILEPSY ON SIBLINGS QUALITY OF LIFE S. Memon*, V. Burch, and K. Das *University of Aberdeen, Aberdeen, UK; Young Epilepsy, Lingfield, UK; and Great Ormond Street Hospital for Children NHS Trust, London, UK
Purpose: Literature examining the effects that epilepsy has on nonaffected siblings is extremely sparse. Therefore, the aim of our study was to assess the quality of life and main concerns of children who have siblings with epilepsy compared to a control group of children who have siblings with other neurological conditions. Method: Cases and controls were prospectively recruited from Young Epilepsy, a centre for children and young people with complex epilepsy and other neurodisabilities. Participants completed a detailed postal questionnaire asking about their concerns. Quantitative and qualitative data was collected. Result: Thirty-one questionnaires were returned from the case group and eight from the control group. Main concerns amongst the cases were injury (89%) or death (77%) of their siblings due to seizures. A greater proportion of cases said that their affected sibling got more attention, but most felt that this was a good thing. Despite the cases having more severe co-morbidities, worries about learning difficulties and behaviour were more common in the control group. Both groups expressed that their sibling's disability had made them more caring and sympathetic, strengthened their family and helped them to deal with stress. Conclusion: Our pilot study found no major differences between cases and controls. Although it is evident that children who have a sibling with epilepsy express some negative effects, including feeling worried about their sibling's well being and health, these individuals also report many positive feelings and on the whole it appears they are functioning well and have a positive outlook on life.
p764 COMPARATIVE EMBEDDED CASE STUDY TO EXPLORE EXPERIENCES OF YOUNG PEOPLE WITH EPILEPSY AND THEIR PARENTS DURING TRANSITION FROM CHILDREN TO ADULT EPILEPSY SERVICES S. A. Lewis Walton Centre NHS Foundation Trust and Bangor University, Conwy, UK
Purpose: This study explores 1) Young people with epilepsy and their parent's experience of communication, information needs and knowledge exchange with healthcare professionals in two epilepsy services. 2) Which models of service delivery was effective during transition from children to adult epilepsy services. Method: Comparative embedded case study design using multiple sources of evidence. Ethical approval was obtained and 30 young people with epilepsy aged between 13 and 19 years old and 21 parents participated. Primary source of data collection methods were individual interviews and focus groups. Two staged approach was used to analyse data; firstly thematic analysis of case study data and secondly pattern matching and replication logic. Theory-based evaluation methods was used to conEpilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x
p766 PARENTAL REACTIONS IN BENIGN CHILDHOOD FOCAL SEISURES T. Valeta St.ThomasHospital, London, UK
Purpose: To document Parental Reactions and Needs in Benign Childhood Focal Seizures (BCFS).
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Method: My personal interest started in 2000 when speaking extensively with parents of children with BCFS I realized that they were concerned for many more issues than the seizures themselves and other than those that they were discussing with their physician. They had dramatic experiences and many unanswered questions and anxieties. Consequently, I have designed a questionnaire and initiated an ongoing prospective study. The questionnaire contains 34 questions aiming to define and analyze the psychosocial effects of BCFS on parents and children, their attitude about epilepsy, their reactions, concerns about the prognosis, necessity of evaluation and needs. Thirty one parents participated in this study. Result: Panic, fear, anxiety, shock, terror and thoughts about death were the most common subjective parental complaints. Their sleep and the quality of their work was affected. Half of the parent's behaviour towards the child changed. Most of the parents expressed the need for education on epilepsies, psychological support for the child, and themselves. They also expressed the need to participate in groups of parents with the same problem. Conclusion: Despite the excellent prognosis of BCFS, parental reactions are severe. There is a need for family management, education and psychological support. That should be properly addressed from the time of first diagnosis and thus eliminate anxiety and improve the quality of life of the child and family.

p768 VAGUS NERVE STIMULATION IN PEDIATRIC EPILEPSY PATIENTS: IS THIS REALLY WORTHWHILE? V. C. Terra, M. A. Nisyiama, A. C. Sakamoto, and H. R. Machado Hospital das Clnicas da Faculdade de Medicina de Ribeiro Preto, Ribeiro Preto, SP, Brazil
Purpose: Intractable epilepsy in children is has a negative impact in cognitive and behavioral skills, and in quality of life. In this aspect, seizure control with minimal side effects should be pursued. In patients that ressective surgery is not possible, alternative treatment such as ketogenic diet or vagus nerve stimulation (VNS) should be considered. Although VNS therapy is available for many years, there are few studies demonstrating its effectiveness in children. Method: We analyzed 36 patients up to 18 years old, with medically intractable epilepsy submitted to vagus nerve stimulator implantation. We considered the age at surgery, the seizure type, the pathological findings, seizure outcome, number of hospitalizations and behavioral changes. Data were prospectively collected, according to the protocols of our institution's ethics committee. Result: 55.6% were boys. A reduction of at least 50% of seizures was achieved in 61.3% of the cases and 12.1% of the patients had more than 90% of seizure frequency reduction. Also, 47.2% of the patients needed frequently hospitalization before VNS implantation and in follow up this number dropped out to 8.3%. The patient who died, one from sepsis and the other in the immediate post-operative period of a callosotomy. Conclusion: VNS demonstrated to be effective in reducing seizure frequency and need of hospitalization in children with very refractory epilepsies and should be considered as an option even in countries with limited resources.
p767 VIDEO-EEG MONITORING IN DIAGNOSTICS OF EPILEPTIC AND NON-EPILEPTIC PAROXYSMAL CONDITIONS IN CHILDREN V. I. Guzeva, and O. V. Guzeva Saint-Petersburg pediatric medical academy, Saint-Petersburg, Russian Federation
Purpose: The aim of the study was to determine the diagnostic efficiency of video-EEG monitoring in children with paroxysmal disorders of consciousness. Method: The study included 259 children from 1month to 18 years, among them 103 (39.8%) were girls and 156 (60.2%)- boys. All children were referred to nervous diseases department to clarify the diagnosis and selection of appropriate treatment. 80.69% of children admitted with diagnosis epilepsy, 19.31%- with non-epileptic paroxysms. Result: The results of comprehensive survey based on video-EEG monitoring allowed to established in 163 (62.93%) cases epilepsy, mostly symptomatic, in 66 (40.49%) partial and in 16 (9.82%)- generalized form. In 68 (41.72%) cases was diagnosed cryptogenic partial epilepsy, in 3 (1.84%)- Landau-Kleffner syndrome and in 10 (6.14%)- idiopathic epilepsy. Diagnosis of non-epileptic paroxysms was specified in 96 (37.07%) cases. Among them 44 (45.83%) were sleep disorders (parasomnias), 21 (21.88%)- neurotic states, others non-epileptic paroxysms established in 26 (27.08%) and ADHD- in 1 (1.05%) cases. Was found a significant difference in frequency of identification of epileptiform activity on EEG with video monitoring during sleep compared with other variants of EEG recording. Detection of epileptiform and epileptic activity during video-EEG monitoring compared with routine EEG increases in 3.7 times. Conclusion: Using the results of video-EEG monitoring (awake and sleep) significantly increases the possibility to correct diagnosis and appropriate treatment. Invaluable help in differential diagnostics of epileptic and non-epileptic paroxysms and clarification forms of epilepsy in children provides the registration of the paroxysm during video-EEG monitoring.
p769 THE EFFECT OF BODY TEMPERATURE IN SEIZURES ASSOCIATED WITH ROTAVIRUS GASTROENTERITIS Y. S. Kwon*, B. Kang*, and D. W. Kim *Inha University Hospital, Incheon, Korea; and Inje University Ilasnbaik hospital, Goyang, Korea
Purpose: To evaluate the effect of body temperature in seizures associated with rotavirus gastroenteritis. Method: Medical charts of infants and children who had been admitted to the pediatric department of Inha University Hospital between July 1999 and June 2011 due to seizures associated with rotavirus gastroenteritis were reviewed. Subjects were initially divided into two groups on the basis of the presence/absence of fever during seizure; febrile seizure, afebrile seizure. Afterwards, subjects in the afebrile seizure group were divided into two subgroups according to the presence/absence of fever during the entire period of illness; afebrile seizure with fever, afebrile seizure without fever. Comparison between the three groups was carried out. Result: Among the 75 patients that were admitted due to seizures associated with rotavirus enteritis, 17 patients (23%) were included in the febrile seizure group and 42 patients (56%) in the afebrile seizure group. Among the afebrile seizure group, 19 subjects (32%) had fever during the illness, while 23 subjects (39%) were afebrile during the illness. Patients with febrile seizures were most likely to develop seizure earlier, while afebrile seizure patients without fever during the illness were most likely to develop seizure later (1.290.77 vs. 2.470.90 vs. 3.090.95 days; p<0.0001). Episodes of seizure were less frequent in the febrile
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seizure group showing significant difference (1.71.0 vs. 2.81.1 vs. 3.31.8 episodes; p<0.01). Conclusion: Results of our study has revealed that body temperature may influence the characteristics of seizures associated with rotavirus enteritis, in which differences of the degree of inflammation may play a role. Further studies in the future are needed to clarify this difference. of the study group) in the following areas: globus pallidus (2 children), subcortical white matter (1 child), hippocampus (1 child), cerebellum (1 child). Early seizures were presented in all children, late seizures (above 7 days after CO poisoning) were identified in 7 children. The clinical presentation of late seizures was tonic clonic seizure (5 children) and mioclonic seizures (1 child). Loss of consciousness were in 10 children (62.5%). Four children developed epilepsy during 2 years after CO poisoning. Conclusion: Severe and medium degree of CO in blood may cause late seizures and trigger epilepsy, especially in the group of young children. Delayed neurologic sequelae (DNS) were a high risk factor of epilepsy. Hyperbaric oxygen therapy is recommended in patient with DNS and CO intoxication related unconsciousness.
p770 ELECTRO-CLINICAL ASPECTS OF FOCAL SYMPTOMATIC EPILEPSY OF CHILDHOOD WITH SECONDARY BILATERAL SYNCHRONY PHENOMENON ON EEG A. Bunduchi*, A. Bunduchi, and S. Hadjiu* *State University of Medicine and Pharmacy, Nicolae Testemit u, Moldova u, Moldova; and Chis ina anu, Chis ina
Purpose: To identify seizure semiology and EEG patterns in children with focal symptomatic epilepsy. Method: Study included 65 patients 38 boys and 27 girls, age 4 months to 18 years, followed-up 6 months to 4 years; divided in 2 groups according to the age at seizures onset. Patients were evaluated neuropsychological, by neuroimaging (neurosonography, CT or MRI) and video-EEG monitoring (112 hours). Result: Semiology of onset seizures was: febrile seizures - 12% cases (I group), GTCS in 21% (I group) and 46% (II group), tonic seizures in 32% (I group) and 2% (II group), atypical absences in 20.9% (I group) and 18% (II group), and partial seizures 18% (I group) and 31.1% (II group). Three seizure types occured in 28% cases (I group) and 26% cases (II group); two types - in 64% patients (I group) and 35% cases (II group), single seizure type - in 17% cases (I group) and 8% cases (II group). Neuropsychological tests revealed cognitive impairment in 82% (I group) and 42% (II group). Interictal EEG changes were represented by: basic EEG slowing, theta-delta regional slowing, regional epileptiform activity combined with diffuse epileptiform patterns secondary bilateral synchrony phenomenon. Ictal patterns include atypical absences (24%), myoclonic seizures (8%), eyelids epileptic myoclonus (2%), and tonic seizures (21%). Conclusion: Focal symptomatic epilepsy associated with secondary bilateral synchrony phenomenon on EEG includes a large polymorphism of epileptic seizures, cognitive impairment and has a poor outcome. EEG changes are represented by regional epileptiform activity combined with diffuse epileptiform patterns.
p772 AUTOANTIBODY TO GLUTAMIC ACID DECARBOXYLASE IN A 2-YEAR OLD GIRL WITH THERAPYRESISTANT EPILEPSY S. Saltk, and E. Y. Karatoprak Istanbul Medeniyet University Goztepe Educational and Training Hospital, Istanbul, Turkey
Purpose: Glutamic acid decarboxylase is the enzyme that synthesis gamaaminobutyric acid which is the major inhibitory neurotransmitter in CNS. Increased titres of Glutamic acid decarboxylase (GAD) antibodies is common in type 1 diabetes mellitus patients. High anti-GAD titres is rarely seen in neurological disorders such as epilepsy. In this study, we report a case presenting with drug-resistant epilepsy with a high titer of anti-GAD antibodies as an unusual cause of epilepsy since she was the youngest case in the literature to our knowledge. Method: A 2-year-old girl with a history of frequent complex partial seizures for 2 days was admitted to our child neurology deparment. To find out the cause of the epilepsy, all routine blood tests, imagings were detected and antiepileptic treatment was started. Result: Seizures which lasts 30 seconds2 minutes were 310 times in a day. Neurological examination, laboratory findings, metabolic analysis, neuroimaging findings and sleep electroencephalography (EEG) were found all normal. Her seizures did not respond many anti-epileptic drug therapy. A high titer of anti-glutamic acid decarboxylase (GAD) antibodies was detected in the patient's serum but not in cerebrospinal fluid (CSF). Seizures responded to intravenous immunoglobulin treatment. Anti-thyreoperoxydase (TPO-Ab) positive hypothyroidism was also detected. Conclusion: In conclusion anti-GAD antibodies should be investigated in drug-resistant epilepsy even in younger children.
p771 CARBON MONOXIDE AND SEIZURES IN CHILDREN A. Gniatkowska-Nowakowska Outpatient Clinic of Child Neurology and Epileptology, Kielce, Poland
Purpose: Carbon monoxide (CO) poisoning has many severe complications. Between them is the stimulation of early and late seizures in children group Method: We respectively reviewed 16 patients who had seizures after CO intoxication. There were 9 girl and 7 boys with a mean age of 9.1 (range 2 to 17 years). The observation time for those patients was 5 years after the poisoning Result: A total 16 children with early seizures were analyzed. During the observation time there was no deaths among the study group. A magnetic resonance scan of the brain (1.5T) was performed 6 months after the CO poisoning. It revealed abnormalities in the brains of 5 children (31%
p773 ATYPICAL EVOLUTION OF PANAYOITOPOULOS SYNDROME INTO CHILDHOOD ABSENCE EPILEPSY: A CASE REPORT K. Skiadas, T. Tsaprouni, and A. Covanis St. Sophie's Paediatric Hospital, Athens, Greece
Purpose: Panayiotopoulos syndrome (PS) is a benign childhood focal epilepsy, which manifests primarily with autonomic, mainly emetic symptoms and has a very good prognosis. Childhood absence epilepsy is idiopathic generalized epilepsy characterized by typical absence seizures associated with bilateral, synchronous and symmetric generalized spikeand-wave discharges at 3 cycles per second. Method: We report a seven year old boy with clinical and electroencephalographic features of PS that showed atypical evolution. He is a
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right-handed neurologically normal boy with unremarkable personal and family history. At the age of 4 years, during nocturnal sleep, he presented with an episode during which his eyes and head deviated to the left, followed by vomiting and impairment of consciousness. This episode lasted ten minutes. The EEG showed right temporal occipital spikes followed by slow waves. This type of seizure was repeated on three occasions within six months and the child was put on carbamazepine. Result: He had been seizure-free for two years when during a follow-up video-EEG recording episodes of absences in association with generalized spike-and-wave discharges 2.5cycles per second of 56 seconds duration, were recorded. In addition, the interictal EEG continue to show right temporal occipital spikes followed by slow waves. The absence seizures were treated with valproic acid and carbamazepine was withdrawn, with complete response. Conclusion: The presence of childhood absence epilepsy in children who initially present with PS is very rare. It is difficult to understand the coexistence, in the same patient, of the two different types of epilepsy. Probably there is a genetic relationship between them.
p775 CLINICAL FEATURES AND OUTCOMES IN FEBRILE INFECTION-RELATED ACUTE EPILEPTIC ENCEPHALOPATHY J. Garca-Peas*, S. Aguilera-Albesa, J. Domnguez-Carral*, M. Yoldi-Petri, T. Dur-Trav, A. Duat-Rodrguez, and M. L. Ruiz-Falc *Marqus de Valdecilla Hospital, Santander, Spain; Navarra Hospital, Pamplona, Spain; and Nio Jess Hospital, Madrid, Spain
Purpose: The term febrile infection-related epilepsy syndrome (FIRES) has been proposed to characterize the features of patients with acute epileptic encephalopathy during a febrile infection. A common aetiology remains obscure. Method: This retrospective multicenter case series reports on the clinical characteristics and outcomes of six patients with acute epileptic encephalopathy. Result: Six previously healthy boys with a median age of eight years (5 12) presented to hospital with generalized tonic-clonic or secondarily generalized seizures that appeared 210 days after initial symptoms of febrile infection. All cases developed refractory epileptic status with a median duration of 30 days (1460) and required barbiturate-induced coma (047 days). Adjuvant immunotherapy were administered in all. In two cases, reversible hepatic failure were noted. Initially, electroencephalography showed diffuse slowing. Persistent bifrontal or fronto-temporal discharges occurred later on. Ancillary studies including blood, urine, and cerebrospinal fluid samples, muscle mitochondrial studies and genetic mutation analysis (POLG1 and SCN1A) were unrevealing. Cerebral magnetic resonance imaging showed non-specific frontal abnormal signals in three patients. Left frontal hypoperfusion was detected by SPECT in one case during the acute phase. All six patients experienced focal refractory seizures during follow-up (684 months). Motor handicaps and mild to moderate cognitive decline were noted in 4 patients. Two children had severe sequelae. Their behaviour was hypoactive or impulsive (50%). Conclusion: The clinical profile and outcomes of these six patients is similar to the previously described as FIRES. This epileptic encephalopathy has an abrupt onset and is followed by refractory focal epilepsy of frontal predominance.
p774 CLINICAL AND ELECTROPHYSIOLOGICAL CHARACTERISTICS OF PATIENTS WITH PAROXYSMAL DISORDERS. CLINICAL-ELECTROPHYSIOLOGICAL CHARACTERISTIC OF PATIENT WITH PAROXYSMAL DISORDERS M. Y. Fomina Pediatric Academy, Sanct-Petersburg, Russian Federation
Purpose: Structure of paroxismal disorders of children Method: Clinical examination, EEG, MRI scan Result: In St. Petersburg State Pediatric Medical Academy from 2009 to 2011 were examined in 1286 patients aged 1 month to 18 years. The survey was conducted neurologist, specialist functional offices, laboratory and MRI diagnostics. Paroxysmal disorders and identified changes during the EEG served as a pretext for seeking advice from 425 people (33%). Complaints about the delay in psychomotor and language development, sleep disorders, behavioral changes, headache, dorsalgia, dizziness, tics, enuresis, at least - progressive motor, visual, or cognitive impairment, reported in 726 people (56.5%). 79 (6.2%) patients were examined in connection with a closed head injury. In the structure of a violation of paroxysmal epileptic paroxysms in our study were 51.2%. Of the 326 children with paroxysmal disorders established diagnosis of epilepsy in 167 cases, the debut of the disease was recorded in 59 children, others have already asked for specialized medical care. Antiepileptic therapy received 77 patients, 19 patients did not take drugs or violating their assigned mode of reception of anticonvulsants. As for the single epileptic paroxysm checked with 12 patients (7.1%). Dominated by partial symptomatic epilepsy with frontal and temporal localization of the source. Among the generalized idiopathic form usually diagnosed in children and absans and juvenile myoclonic epilepsy. Symptomatic generalized epilepsy syndromes are West and Lennox-Gastaut syndrome. West syndrome - the age-dependent epileptic syndrome related to the group of infantile epileptic encephalopathy was diagnosed in three infants. The patients were symptomatic infantile spasms and mental regression and motor skills. Lennox-Gastaut syndrome was observed in one patient. Early infantile epileptic encephalopathy syndrome (Otahra) recorded in the patient at age 3 months, suffered a hypoxic-ischemic CNS damage severe. Benign epilepsy of infancy (Watanabe's syndrome) was diagnosed in two patients 5 and 7 months. Among the most common non-epileptic seizures recorded syncope, parasomnias, and affective-respiratory attacks. Conclusion: In structure of paroxismal disorders in our study the epileptic paroxisms made 51%/ Among them the domineering ones were partial symptomatic epilepsies (68%).
p776 EARLY ONSET OF CORTICAL THINNING IN CHILDREN WITH ROLANDIC EPILEPSY G. M. Overvliet*, R. Besseling, S. V. D. Kruijs, J. Vles, J. Jansen, P. Hofman, S. Ebus, A. De Louw, A. Aldenkamp, and W. Backes *Maastricht University Medical Center, Maastricht, The Netherlands; and Kempenhaeghe, Heeze, The Netherlands
Purpose: Rolandic epilepsy is an idiopathic childhood epilepsy associated with language impairments. It is investigated whether Rolandic epilepsy is associated with abnormalities in cortical thickness, and whether these abnormalities are associated with declined language performance. Method: 24 children (age 814 years) with a clinical diagnosis of Rolandic epilepsy were compared with 24 age-matched healthy controls. The Clinical Evaluation of Language Fundamentals (CELF) test was used for language evaluation. Structural T1-weighted MRI was performed at 3 Tesla (voxel size 1x1x1 mm3) to enable automated quantitative assessment of cortical thickness. Linear regression was used to test for differences between patients and controls and to assess the effect of age and language indices on cortical thickness. Result: For patients the core language score (meanSD: 9218) was lower than for controls (10611, p=0.0026) and below the norm of 100
226 Abstracts
(p=0.047). Patients showed specific impairments with respect to the norm in receptive language (8719, p=0.002) and language content (8718, p=0.0016). The cortex in patients was significantly thinner (p<0.05, multiple-comparisons corrected) in the postcentral, supramarginal and superior temporal gyrus of the left hemisphere (receptive language area). Predominantly in left fronto-temporal regions, significant cortical thinning with age was found in patients only. Conclusion: Reduced cortical thickness was found in Rolandic epilepsy in a language mediating area. Furthermore, early onset of cortical thinning was observed in multiple language mediating areas. These abnormalities represent subtle but significant pathomorphology of the language system and suggest thatRolandic epilepsy should not be considered merely as a benign condition. Purpose: The aim was to assess the guideline compliance and outcomes of pre-hospital and Emergency Department (ED) treatment of prolonged convulsive epileptic seizures in children. Method: This retrospective observational study included all children under 18 years attending a teaching hospital ED who were treated for prolonged convulsive seizures 21-11-2010 to 21-11-2011. Cases were ascertained from the electronic database and medical notes were reviewed, data captured with a standard proforma, and transferred to an SPSS database. The local departmental and United Kingdom guidelines were the audit standards, and outcomes compared to the literature. Simple descriptive statistics, Chi-squared, and independent samples t-test were used. Result: There were 43 episodes in 37 patients, 20 male (54%) aged 10 months to 16 years (median 4 years). Of 76 children given pre-hospital treatment and presenting to the ED during this period, 49 (65%) had stopped seizing and 27 were still seizing and so received treatment in the ED. About half had Rectal Diazepam from the ambulance crew, half Buccal Midazolam (BM) from their carers. Only 16 (37%) of the children's episodes treated in ED had had no pre-hospital emergency treatment. 25/ 43 (58%) treatments in ED (90% BM) stopped the seizure within 10 minutes, 7/25 relapsed within 1 hour, 9/43 required respiratory support, 13 were admitted to Paediatric Intensive Care. BM doses were often lower than recommended, and iv phenytoin often delayed, while paraldehyde was given. Conclusion: Pre-hospital treatment was effective. ED treatment often under-dosed BM, and the use of phenytoin was often delayed: practices that will be addressed locally.
p777 BUT DOES MY DAUGHTER NOT SUFFER A MITOCHONDRIAL DISEASE? CO-MORBID DRAVET SYNDROME M. Ruz-Falc-Rojas*, V. Cantarin-Extremera*, J. GarcaPeas, A. Duat-Rodriguez1*, L. Lpez-Marn*, and L. Gonzlez-Gutirrez-Solana* *Nio Jesus Hospital, Madrid, Spain; and Marqus de Valdecilla Hospital, Santander, Spain
Purpose: Dravet syndrome is a catastrophic epilepsy syndrome with cognitive delays and autistic behaviour. It is associated with mutations in the SCN1A gene. A similar clinical feature is found in patients with mitochondrial disease, this causes confusion and diagnostic delays. Method: This a case report Result: Around 3 months of age after the first vaccine of polio-DTP, the patient presented status epilepticus with no fever. During her first year of life she had hemiclonics seizures, every 24 weeks, and other seizures with variable features, with and without fever. When she was 78 months she had myoclonics too. She had normal psychomotor development until she was 6 months of age, after that she had a motor and language delay. The complete diagnostic evaluation included: a cranial magnetic resonance, cariotypes, a metabolic disease studyall were normal. When she was 4 years old, a muscle biopsy demonstrated complex IV dysfunction. In this patient, when valproic acid decreased from 100 mg/l, the seizures increased. We reviewed her medical history and suspected a feature consistent with the Dravet syndrome. A mutation in SCN1A was found. Conclusion: Our patient underscores the need to rule out possible comorbid mitochondrial disease and Dravet syndrome. This is important because the treatment for each type of seizure is different, with valproic acid being first line treatment in Dravet syndrome and contraindicated in many mitochondrial diseases. Failure to pursue complete diagnostic evaluation might influence in medication choice, possible seizure control and developmental outcomes. Nowadays, there is not an entirely obvious explanation for this association.
p779 APPLICATION OF NEW ILAE CRITERIA FOR DRUG RESISTANT EPILEPSY IN CHILDREN IN CLINICAL PRACTICE M. A. De La Morena Vicente, J. Herreros Rodriguez, A. Garcia Ron, R. Blanco Lago, L. Ballesteros Plaza, and J. Jensen Veron Hospital Universitario Infanta Cristina, Madrid, Spain
Purpose: The International League Against Epilepsy (ILAE) has proposed new criteria to define drug resistant epilepsy. Epilepsy in children displays clinical and therapeutic differences with respect to adults. We have applied these criteria to our outpatients pediatric. Method: We reviewed medical records of forty children with epilepsy on our database, we excluded patients with less than one year of follow up, with only one seizure or febrile seizures. Result: Level 1 for categorizing of treatment outcome, we described the above mentioned category in the last visit. With respect to seizure control: Category 1, seizure free (50%); Category 2, treatment failure (20%); Category 3, undetermined (30%). Each category is subdivided into A (no), B (yes), C (undetermined) based on outcome with respect to adverse events: 1A (47.5%), 1B (0%), 1C (2.5%), 2A (12.5%), 2B (5%), 2C (2.5%), 3A (22.5%), 3B (0%), 3C (7.5%). For Level 2 classification of drug responsiveness of epilepsy, we obtained the following data: drug responsive (50%), drug resistant (22.5%), undefined (27.5%). Considering the pharmacological treatment, 52.5% was in monotherapy and 47.5% in combination: drug responsive (40% and 10%), drug resistance (0% and 22.5%), undefined (12.5% and 15%) respectively. Conclusion: This study shows a greater number of patients classified as undefined with respect to studies in adults, and demonstrates the difficulties of application of these criteria in pediatric patients. It would be interesting that future studies included both populations.

p778 A CLINICAL AUDIT OF PROCESS AND OUTCOME OF EMERGENCY TREATMENT FOR PROLONGED EPILEPTIC SEIZURES IN CHILDREN ATTENDING AN EMERGENCY DEPARTMENT E. Joslin*, C. Dieppe, and W. P. Whitehouse* *University of Nottingham, Nottingham, UK; and Nottingham University Hospitals, Nottingham, UK
227 Abstracts
p780 VAGUS NERVE STIMULATION IN A NEW PATHWAY WITH ANTI-INFLAMMATORY CYTOKINES V. Cantarin-Extremera*, M. Ruz-Falc-Rojas*, M. RamirezOrella*, J. Asensio*, M. Prez-Jimnez, A. Duat-Rodriguez1*, and B. Rivero* *Nio Jesus Hospital, Madrid, Spain; and Hospital Infantil Universitario Nio Jess, Madrid, Spain
Purpose: Electrical stimulation of the vagus nerve is a treatment for patients with refractory epilepsy and depression. An anti-inflammatory pathway has been identified recently. In a few articles, a significant increase in circulating cytokines after vagus nerve stimulation treatment was observed. We want to know mechanism may occur via vagally mediated actions on cytokine synthesis. Method: Prospective study with 5 patients with refractory epilepsy, and future candidates will be added. The period studied is from one week average prior to, and 1, 3 and 6 months following, implantation of a vagus nerve stimulator (VNS). No medication changes were made during the course of the study. High-sensitivity ELISA kits were used to measure plasma IL-6, IL-10 and IL-8. Cortisol, C-reactive protein (CPR) and immune reconstitution were measured. We measured same cytokines in control group with VNS implantation more than 2 ayes ago. Result: There was significant decrease in the plasma levels of IL-6. Increases seen with IL-8 and cortisol were not significant. IL10 was similar. Plasma CRP and levels of CD4 and CD8 lymphocytes were unchanged. All patients had seizures reduction. Conclusion: VNS is associated with peripheral decreased in antiinflammatory circulating cytokines. Such changes are unlikely to be nonspecific inflammatory reactions, reflected by CRP levels. In view of gathering evidence supporting a role for the immune system in modulating affect, as well as seizure activity, these effects of VNS may be therapeutically relevant. These data require replication in a larger, controlled study. ICU admission. Children who made a full recovery did so within 6 months, which suggests that all children with encephalitis should be monitored for 6 months after the acute illness.
p782 STRESS SENSITIVITY OF CHILDHOOD EPILEPSY: WHICH CHILDREN SEIZE UNDER STRESS? J. S. Van Campen, F. E. Jansen, L. C. Steinbusch, M. Joels, and K. P. J. Braun Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands
Purpose: To address the effect of stress on seizure frequency in children with epilepsy and evaluate which clinical characteristics of these children relate to stress sensitivity of seizures. Method: Parents or caregivers of children with active epilepsy (aged 2 to 16 years) were sent questionnaires on epilepsy characteristics, anti-epileptic treatment, psychomotor development, life-time stress exposure, and the effect of stress on seizure frequency in their child. Stress sensitivity of seizures was divided in increased seizure frequency during stressful periods, and seizures provoked by acute stress. The relations between patient and epilepsy characteristics and stress sensitivity of seizures were analysed using multivariable regression models. Result: Hundred-fifty-three children were included in this study of whom 51% reported precipitation of seizures by stress. An increase in seizure frequency during periods of stress was reported in 39% of children. Seizures precipitated by acute stress were reported in 37%. There was a large overlap between patients reporting emotional and patients reporting physical stress to be a precipitating factor. A higher number of negative life events experienced in total life was related to an increase in seizure frequency in stressful periods (OR 1.3, p=0.011) as well as to precipitation of seizures by acute stress (OR 1.3, p=0.020). Conclusion: Stress sensitivity of seizures is very often reported and seems to be related to experienced negative life events. This relation may be explained by a changed regulation of the hypothalamic-pituitary-adrenal axis by (early life) stress. A larger hormonal response to daily stressors then increases the likelihood of stress to induce epileptic seizures.
p781 THE PROGNOSTIC FACTORS OF ACUTE ENCEPHALITIS IN CHILDREN J. S. Lee, J. W. Kang, H. Kang, and H. D. Kim Severance Children`s Hospital, Seoul, Korea
Purpose: The long term outcome of acute encephalitis is very variable. The purpose of our study was to evaluate the prognostic factors that can influence to patient`s prognosis. Method: Of 157 children who were admitted for acute viral encephalitis from 2006 to 2011, 78 children were qualified for follow-up evaluations. We divided patient's group into favorable outcome (n=48) and poor one (n=30). We compared the etiologies, clinical courses, the neuroimaging and electroencephalographic findings between two groups. Result: The etiologies were identified in 17 cases in CSF (24%). The main associated agents were herpes simplex (9 children; 53%), enteroviruses (3 children; 18%), varicella-zoster (1 child; 5.5%), measle virus (1 child; 5.5%), and bacterias (3 children; 18%). 73 patients showed abnormal electroencephalographic findings (94%). The most common complications were cognitive dysfunctions (60.8%), and seizure disorders (50.6%). The significant risk factors in poor group were initial history of seizures (p=0.04), status epilepticus (p=0.03), mood change (p=0.009), cognitive dysfunction (p=0.018), and ICU admission (p=0.0326). As the initial time of immunoglobulin treatment is earlier, the prognosis were better (p=0.037). Conclusion: About 30% of children presented persisting sequelae after encephalitis. The significant risk factors for sequelae were initial history of seizure, cognitive problems, and mood change, status epilepticus and
p783 ABSENCE SEIZURES DURING AWAKE AND SLEEP: WHAT IS A DIFFERENCE? B. Jocic-Jakubi, A. Al Tawari, L. Cindro Heberle, M. Pavlovic, and J. Ibrahim Al Ansari Al Sabah Hospital, Kuwait City, Kuwait
Purpose: To analyze neurophysiological features of absence seizures during awake and sleep. Method: Thirty-six children (27 girls, 9 boys) aged 413 years with absence epilepsy had routine 21-channel EEGs performed according to the international 1020 system. All children had both sleep and awake recodring including HV and IPS. The average length of EEG recording was 60 minnutes (between 40 and 90 minutes). All recorded absence seizures were reviewed by two epileptologists. Electroclinical found during the GWS discharges in sleep were compared to the electroclinical features of the patient's awake absence seizures. Result: 176 short paroxysms of GSW<2sec (113 spontaneous and 63 during HV), and 222 long paroxysms of GSW lasting 335 seconds (132 spontaneous and 90 during HV, respectively) were recorded. IPS provoked PPR in 10 patients (28%). During sleep 477 short and 193 long paroxysms of GWS were recorded, respectively. Interictal focal epileptiform abnormality was noted in 9 patients (25%) during awake and in 16
228 Abstracts
(44%) patients during sleep. Bifrontal onset of absence was revealed in 6, left frontal in 2 and right frontal in 5 patients. A clinical sign was seen in 10 (28%) patients during sleep (staring look, blinking, eyelid and brow jerks). Conclusion: Short GSW < 2 sec were mainly recorded during sleep, while longer GSW paroxysms were presented during awake registration. Interictal focal abnormality was frequently seen during sleep. Either bifrontal or unilateral frontal onset of absence was found in 1/3 of patients. Method: 23 children with Rolandic epilepsy (age 11.4 2.0 years) and 21 age and gender matched healthy controls (age 10.3 1.7 years) underwent testing of language using the CELF-4. Task functional MRI was performed using a covert word generation task, a text reading task and a finger tapping task. ROIs were used to assess laterality index distributions of the activation for the word generation and reading task and to perform a functional connectivity analysis based on correlation of ROI averaged resting state fMRI time series. Result: The lateralization index showed that both the word generation task and reading task elicited bilateral activation with some predominance for the left hemisphere. In comparison to controls, patients showed decreased functional connectivity between the left sensorimotor cortex and the right inferior frontal cortex and increased connectivity between the left anterior cingulated cortex and bilateral temporal regions. Conclusion: The aberrant connections found indicate a disturbed involvement of prefrontal and temporal language areas in Rolandic epilepsy. In particular, the aberrant interhemispheric connection between the left sensorimotor area and the right inferior frontal cortex suggests a pathway through which epileptiform activity from Rolandic strip can adversely affect language function.
p784 EPILEPSY OF INFANCY WITH MIGRATING FOCAL SEIZURES- EXPANDING THE PHENOTYPE AND EXPLORING THE AETIOLOGY A. Mctague*, R. Kneen, M. Kurian, R. Appleton, and H. Cross* *UCL-Institute of Child Health, London, UK; Alder Hey Children's NHS Foundation Trust, Liverpool, UK; and UCLInstitute of Child Health, London, UK
Purpose: Epilepsy of infancy with migrating focal seizures, previously known as migrating partial seizures of infancy, is a rare early infantile epileptic encephalopathy (EIEE). We describe novel clinical, MRI and EEG features and discuss the relationship of this disorder to other EIEE phenotypes . Method: Eighteen cases were reviewed; 14 referred via the British Paediatric National Surveillance Unit (BPNSU) Study (a monthly survey of consultants in Paediatric Neurology in the UK and Republic of Ireland undertaken between April 2008 and April 2010) and 4 by personal communication. Data were collected using anonymised questionnaires. Result: We present the findings from our cohort of 18 patients. New clinical features included: severe gut dysmotility (N=3) and a movement disorder (N=3). Previously unreported EEG findings include hypsarrhythmia in 4(associated with infantile spasms in 3) and burst-suppression in 3. Abnormal myelination on cerebral MRI was seen in 4 patients with a particularly striking deficiency of myelination of the deep white matter in 1 of these 4. MRS in 3 demonstrated decreased N-acetyl aspartate suggesting failure in brain maturation. One patient had putaminal atrophy on MRI and post-mortem examination. SCN1A testing in seven patients was negative. Molecular genetic investigation (using an early infantile epileptic encephalopathy gene panel and whole exome sequencing strategy) is currently underway. Conclusion: Epilepsy of infancy with migrating focal seizures is an agerelated electro-clinical syndrome which may evolve both into, and from, other EIEE syndromes including West syndrome. Further elucidation of the molecular genetic basis may confirm shared disease mechanisms between the different EIEE phenotypes.
p786 CLINICAL PROFILE OF PSYCHOGENIC NONEPILEPTIC SEIZURES IN CHILDREN AND ADOLESCENTS: A STUDY OF 37 CASES M. Gupta, Y. Patidar, G. A Khwaja, D. Chowdhury, A. Batra, and A. Dasgupta G.B.Pant Hospital, New Delhi, India
Purpose: To study the clinical and video-EEG profile of pediatric and adolescent patients with Psychogenic Nonepileptic Seizures (PNES) Method: All patients below 18 years of age with clinical suspicion of PNES were included in the study. After history and clinical examination; all were confirmed by induction either during video-EEG monitoring or bedside. After proper disclosure of diagnosis, nonstructural psychotherapy and appropriate medications was given. Result: Out of 37 patients, 24 (64.85%) were females and 13 (35.15%) were males. M:F ratio in age group <12 years was 3:1 whereas, in the 13 18 year group it was 1:1.8. The mean age was 14.7 years and mean duration of illness was 13.7 months. 29 (78.38%) were students, while 8 (21.62%) were school dropouts. 5 (13.5%) had coexisting epilepsy, whereas 32 (86.5%) had only PNES. Among 32 patients with only PNES 17 (53.12%) were on antiepileptic drugs. Patients were divided into: Group A (motor attacks: 35.15%), and Group B (limp attacks: 64.85%). Common features were pre-ictal headache, resistant behaviour, ictal eyes closure, partial responsiveness, teeth clenching, lying limp for variable duration, waxing-waning pattern, and asynchronous movements. History of emotional abuse was present in 11 cases (29.73%), physical and emotional abuse in 8 (21.62%) and physical and sexual abuse in 6 cases (16.2%). Conclusion: PNES is common, but frequently underdiagnosed in pediatric and adolescent population. A high index of clinical suspicion and confirmation by video-EEG is diagnostic. An early diagnosis, identification and counselling can improve their outcome and prevent unnecessary usage of antiepileptic medications.
p785 ABERRANT FUNCTIONAL CONNECTIVITY BETWEEN SENSORIMOTOR AND PREFRONTAL CORTEX REGIONS IN ROLANDIC EPILEPSY G. M. Overvliet, R. Besseling, J. Jansen, J. Vles, P. Hofman, A. Aldenkamp, and W. Backes Kempenhaeghe, Heeze, The Netherlands
Purpose: Children with Rolandic epilepsy frequently show comorbid language problems. It is unknown how epileptiform activity from the sensorimotor (Rolandic) area might influence distal language areas. To investigate possible neuronal linking between the sensorimotor cortex and language mediating areas, functional connectivity networks were studied by fMRI.
p787 EPILEPSY AND THE IMMUNE SYSTEM ... IS THERE ANTIBODY THERE?... S. Wright*, C. M. Jol-Van Der Zijde, M. J. D. Van Tol, P. Waters*, B. Lang*, O. F. Brouwer, and A. Vincent*
229 Abstracts
*University of Oxford, John Radcliffe Hospital, Oxford, UK; Leiden University Medical Centre, Leiden, The Netherlands; and University Medical Centre Groningen, Groningen, The Netherlands
Purpose: Immune mechanisms are thought to be involved in the pathological disease process in a significant number of childhood and adult epileptic syndromes, and in other seizure related disorders (e.g. encephalitis). Of particular interest is the occurence of highly specific autoantibodies to important neuronal proteins (VGKC-complex proteins, NMDAR, AMPAR, GABAbRs) in the blood and spinal fluid in some of these patients. The aim of this study is to examine the sera of newly diagnosed paediatric epilepsy patients for the presence of specific neuronal autoantibodies. Method: This Dutch cohort consists of 178 paediatric patients aged between 1 month and 16 years with newly diagnosed epilepsy. The sera are being tested for antibodies to the NMDA receptor, VGKC-complex and associated proteins (LGI1, CASPR2, contactin-2), GAD and glycine receptor. The presence of antibodies are detected visually using antigen specific cell-based assays (NMDAR, LGI1, CASPR2, contactin-2, glycine receptor), and the levels of antibodies against the VGKC-complex and GAD are quantitated by radioimmunoprecipitation assays. Result: In total, 25/178 patients (14%) have been found to have a positive antibody test so far. The most commonly found antibody is to the VGKC-complex. Conclusion: Preliminary testing of a newly diagnosed paediatric epilepsy cohort has revealed a significant number of patients with potentially pathogenic neuronal autoantibodies in the serum. Further work will include completion of testing for antibodies to the CNS antigens described, a coded comparison with age-matched controls, a search for novel antigenic targets and the correlation of patient clinical features with the presence of a positive antibody. Conclusion: ADHD symptoms are as common in RE as in other epilepsy types but there is no evidence for a specific association with an ADHD subtype. The presence of ADHD symptoms is a marker for psychiatric disturbance regardless of epilepsy status. Physicians managing children with ADHD should screen for and assess behavioural, emotional and psychiatric problems in children with new-onset epilepsy, and bear in mind that ADHD symptoms often herald broader psychopathology and competency issues.
p789 JUVENILE MYOCLONIC EPILEPSY: A FAMILY STUDY E. Cvetkovska, I. Kuzmanovski, T. Cepreganova Cangovska, D. P. Cvetkovska, and B. Boskovski University Clinic of Neurology, Skopje, Macedonia
Purpose: To evaluate clinical features of probands with JME and affected members of their families. Method: Clinical and genealogic data were collected from 12 probands with JME and family members with history of seizures. Result: Mean number of affected individuals per family was three. JME probands group consisted of 3 males and 9 females, age of seizure onset being 8 - 18 years (mean 13, 6 y.). All had myoclonic jerks and generalized tonic-clonic seizures (GTCS); absences were reported in 41%. 22 relatives were found to have seizures, 13 females and 9 males, age at onset 739 years (mean 16, 7 y). In half families, JME was the only clinical feature, in others there were members with other forms of IGE. Totally 13 family members had JME, epilepsy with GTCS only was diagnosed in 2, juvenile absence epilepsy in 2, adult onset myoclonic epilepsy in 1 and indeterminate type of epilepsy remained in 4 of affected individuals. In two multi-generation families, phenomenon of possible genetic anticipation was observed, i.e. the onset of disease had a tendency to decrease in age which each successive generation. Conclusion: Substantial number of families broadly share the same phenotype, but the others appear to have a range of different phenotypes. Roughly uniform age-at-onset was found in majority of families, although phenomenon of possible genetic anticipation was observed in two.

p788 PREVALENCE AND ASSOCIATIONS OF ADHD IN ROLANDIC EPILEPSY B. Mukhtyar*, A. Smith*, T. Clarke, N. Dorta, and D. K. Pal* *King's College London, London, UK; and Columbia University, New York, NY, USA
Purpose: Children with epilepsy have elevated levels of ADHD and psychiatric symptomatology, although the relative profiles for rolandic epilepsy (RE) are not well documented. We assessed prevalence of ADHD and psychiatric symptomatology in RE, and tested the hypothesis of a specific association with hyperactive-impulsive subtype. Method: We prospectively assessed ADHD symptoms among 42 unselected participants in a US genetic study of RE. We used the Attention Disorders Evaluation Scale (ADDES), Brief Rating of Executive Function (BRIEF), and Child Behavior Checklist (CBCL). We calculated standardised scores. Result: Parents rated 19% of RE children symptomatic for ADHD, predominantly combined type using the ADDES; we obtained coherent results from BRIEF and CBCL. Three quarters of children symptomatic for ADHD were rated in the symptomatic range for one or more psychiatric or competency problems, a seven-fold increased risk for DSM disorders compare to RE children without ADHD symptoms. These were mainly in internalising behaviours, somatic symptoms and attention problems.
p790 LEVETIRACETAM MONOTHERAPY IN PATIENTS WITH JUVENILE MYOCLONIC EPILEPSY J. Kim Neurology, Hallym University Sacred Heart Hospital, Anyang, Korea
Purpose: Although valproate is a well-known first-line antiepileptic drug in juvenile myoclonic epilepsy (JME), valproate has a lot of tolerability problems, especially in adolescence and women of childbearing potential. Levetiracetam (LEV) has been reported as one of alternative first-line antiepileptic drugs in JME. We want to describe our experience with LEV monotherapy in young women. Method: We reviewed medical records of patients with JME treated with LEV monotherapy. Result: Among 7 patients [all females, mean age 21.3 years (18~27)], LEV was initial monotherapy in 2, second monotherapy in 4, and third monotherapy in 1 patient. Four patients became seizure free and 3 patients had only myoclonic jerks. No patient had significant adverse events. All patients were subscribed as once-a-day schedule and the average daily doses were 678.5 mg (500~1000 mg). Minimum follow up duration was 18 months.
230 Abstracts
Conclusion: Our report demonstrates good efficacy and tolerability of LEV in JME patients and supports that LEV could be a first-line therapy in JME, especially in women of childbearing potential.
p791 TEMPORAL LOBE EPILEPSY T. Chepreganova-Changovska, E. Cvetkovska, I. Kuzmanovski, and B. Boshkovski University Clinic of Neurology, Skopje, Macedonia
Purpose: Temporal epilepsy is the most frequent form of partial or localized epilepsy and it is considered that is responsible for 60% of the patients with epilepsy. There are two types of temporal epilepsy: the former which affects the medial and internal structures of temporal lobe medial temporal epilepsy, and the latter, which involves the outer structures of temporal lobe neocortical temporal epilepsy. The most frequent form of these two types of temporal epilepsy is medial temporal epilepsy. Method: MRI and EEG findings were evaluated in 30 patients with the diagnosis of TLE (18 females and 12 males, F:M ratio = 1.5), aged from 16 to 57 years, admitted at the Clinic of Neurology, the Unit for Epilepsy, within the period 2009 to 2010. Result: Pathological finding was registered in 75% of patients, 25% had normal finding on MRI. In 13 patients hippocampal sclerosis was found. EEG finding was registered for focal activity in 72% of the patients, with a positive finding for hippocampal sclerosis on the same side. Discharges of the peak-wave complex on the other side of the HS also were registered in two (18%) patients. Dual pathology (+HS) was registered in 2 patients (15.3%). Conclusion: Epileptogenic focus in temporal epilepsies should be the initial ground for its further regular managing, and in some cases for further pre-surgical evaluation.
p793 CLINICAL HETEROGENEITY IN FAMILIAL PARTIAL EPILEPSY WITH AUDITORY FEATURES NEGATIVE FOR LGI1 AND WITH MATRILINEAL INHERITANCE C. Leta*, F. Bisulli*, F. Pittau, L. Licchetta, C. Stipa*, I. Naldi*, L. Alvisi, and P. Tinuper *IRCCS Istituto delle Scienze Neurologiche di Bologna, Universit di Bologna, Bologna, Italy; Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada; Istituto delle Scienze Neurologiche, Universit di Bologna, Bologna, Italy; and IRCCS Istituto delle Scienze Neurologiche, Bologna, Italy
Purpose: Autosomal Dominant Partial Epilepsy with Auditory Features (ADPEAF) is a benign epileptic syndrome characterized by focal seizures with typical auditory auras and/or other symptoms of lateral temporal origin, often followed by secondary generalization. LGI1 mutations have been identified in about 50% of ADPEAF families and genetic heterogeneity has been widely documented. We describe a family with ADPEAF presenting with atypical clinical features, expanding the phenotype of the syndrome. Method: We studied a family of four generations, including 53 individuals, of which seven with epilepsy and six with febrile seizures (FS). All affected members have been clinically investigated and screened for LGI1 mutations. Result: The proband and her daugther presented partial epilepsy with auditory features, associated in the proband with drug-resistance, myoclonus, intentional tremor, sensorineural hearing loss and generalized spike and waves on EEG recording. Two members in the matrilineal line experienced generalized seizures in childhood and three have focal epilepsy. One of them has mental retardation (MR) and died for SUDEP. Genetic analysis failed to disclose mutations for LGI1 in all screened members. Conclusion: This family differs from the classical ADPEAF syndrome, in several peculiar clinical features: presence of IGE (idiopathic generalized epilepsy) trait in the proband, high frequency of FS, seizures characterized by variable phenotype in different members, possible matrilineal inheritance of epilepsy, mental retardation. This phenotypic heterogeneity of the syndrome supports the evidence that gene other than LGI1 are responsible for ADPEAF.
p792 BATHING EPILEPSY TRIGGERED BY EMERSION FROM WATER AND TOWEL WRAPPING: A CASE WITH ICTAL VIDEO-ELECTROENCEPHALOGRAPHIC RECORDING C. Aguiar*, R. Sousa*, A. Maia*, D. Alves, and R. Rego *Hospital de So Joo, Porto, Portugal; and Servico de Neurofisiologia, Porto, Portugal
Purpose: Bathing epilepsy is a rare form of reflex epilepsy. In previously reported cases, onset is during early childhood and seizures are usually triggered by immersion in water. Prognosis is favourable and pharmacological treatment is seldom required. We describe a case fitting this diagnosis but with distinct and peculiar features. Method: Clinical case report Result: 3-year old caucasian male, with normal psychomotor development. The parents reported recurrent episodes of vomiting and drowsiness when taken out of the bath, since the neonatal period. At the age of 2 and a half, the semiology of these bath-related episodes changed, including pallor, loss of contact, hypotonia, and oral automatisms. The only reproducible (and systematic) triggers were emersion from water followed by towel wrapping. Video-EEG recordings confirmed this semiology and showed left frontotemporal ictal patterns. Interictal EEG, brain MRI, and EKG-Holter were normal. The child was started on carbamazepine. During the short follow-up period, response to this drug seems favourable, albeit incomplete. Conclusion: We believe that this video-EEG documented case of bathing epilepsy presents peculiar features worth reporting, including a neonatal onset (with pure autonomic reflex seizures), and triggering by the very specific sequence of emersion from water followed by contact with a towel.
p794 RARE COPY NUMBER VARIANTS IN LENNOX-GASTAUT-LIKE EPILEPSY C. Lund*, E. Brodtkorb, O. Rsby, and K. K. Selmer *Oslo University Hospital, Brum Postterminal, Norway; Trondheim University Hospital, Trondheim, Norway; and Oslo University Hospital, Oslo, Norway
Purpose: Objectives: Lennox-Gastaut syndrome (LGS) is characterized by multiple seizure types, cognitive impairment and specific EEG findings. To explore possible genetic predispositions, we have searched for copy number variants (CNVs). Method: LGS-like epilepsy was broadly defined as at least three different types of generalized seizures, including tonic seizures or the combination of atonic seizures and atypical absence, learning disability, treatment resistance and bilateral epileptiform discharges. Whole-genome array comparative genomic hybridization (aCGH) was performed in 21 consecutive adult patients. Results: Eight patients (38%) carried one or more rare CNVs. All were men; two had single duplications, four had single deletions, one had a duplication and a deletion and one had multiple duplications/deletions.
231 Abstracts
Average CNV size was 997 kb (0.05 kb4.7 Mb). Three patients had CNVs and clinical pictures matching known genetic syndromes; 22q13.3 deletion, 2q23.1 deletion, and MECP2 duplication. Conclusions: Previously, syndromic disorders were identified by their clinical features. The patients in this study were lacking sufficient specific history and features to suggest a genetic or non-genetic cause. However, they were diagnosed with genetic syndromes as a result of genetic testing combined with a consecutive phenotype evaluation. Our study demonstrates the usefulness in identifying the genotype in order to shed light on the phenotype and reveal the etiology in epileptic disorders. ena have been described in idiopathic generalized epilepsies, although they usually were not visual. Method: We present the case of a girl, who developed, at 5 years of age, brief episodes of behavioral arrest with blinking, which were preceded or accompanied by visual phenomena (micropsy and/or blindness). On at least one occasion she had visual symptoms without subsequent loss of conscience. The neurological exam was normal. Result: The EEG showed bursts of generalized 3Hz spike-slow wave complexes, at times starting in the right posterior region, OIRDA, occipital sharp waves with right predominance and a fotoparoxysmal response. Magnetic resonance imaging was normal. On 24 hour-Vdeo-EEG, one brief seizure was recorded, which consisted of repetitive blinking, associated to rhythmic 4Hz sharp waves in the occipital regions. Valproic acid led to seizure control at a dosage of 740mg/day. Conclusion: We present this case as an unusual example of a differential diagnosis to be made between an association of a focal idiopathic epilepsy with a generalized idiopathic epilepsy versus a generalized epilepsy with focal aspects, clinically and neurophysiologically. Prognostic and therapeutic implications of this distinction will be discussed.
p795 CLINICAL AND VIDEO-POLYGRAPHIC FEATURES OF SENILE PROGRESSIVE MYOCLONIC EPILEPSY: A DISTINCTIVE PROGRESSIVE MYOCLONIC EPILEPSY OF ADULT DOWN PATIENTS G. DOrsi*, M. Trivisano, M. G. Pascarella, F. Pacillo*, E. Carapelle, C. Luisi, M. T. Di Claudio, T. Francavilla, A. La Neve, V. Demaio, M. Minervini, and L. M. Specchio *Epilepsy Center, Clinic of Nervous System Diseases, University of Foggia, Riuniti Hospital. Foggia, Italy; Foggia, Italy; Bari Polyclinic, Bari; Polyclinic of Bari, Bari; and Neurological Unit, Bisceglie, Italy
Purpose: Little is known about the clinical and polygraphic features of Senile Myoclonic Epilepsy, a myoclonic epilepsy associated with dementia in adult Down patients. This study investigates the clinical and video-polygraphic features of 8 patients with Senile Myoclonic Epilepsy, focusing on the evolutive aspects of myoclonic epilepsy and dementia. Method: Four women and four men, affected by Down syndrome, 51 70 years old (median 54.6 years), were submitted to clinical and neurophysiological (polygraphic recording with jerk-locked back-averaging) investigations. The mean follow-up was 5 years from dementia onset. Result: Three clinical-polygraphic phases emerged. The first phase was characterized by a late onset (> 50 yrs) of a slowly progressive cognitive decline associated with generalized epileptiform abnormalities during sleep. After about one year, there was a gradual onset of second phase with a worsening of cognitive disorders associated with myoclonic seizures, usually occurred on awakening, and/or occasional generalized tonic-clonic seizures. Polygraphic features showed generalized fast spike-waves with bilateral myoclonic jerks, especially at awakenings. Finally, a third phase followed with dementia, ataxia, myoclonus and photosensitivity with rhythmic myoclonic jerks at a frequency of 1224 Hz. Burst-locked electroencephalographic averaging generated a controlateral positive-negative central transient preceding the myoclonus EMG discharge by 2024 ms, compatible with a cortical origin. Conclusion: Our patients showed a distinctive clinical - polygraphic picture (myoclonus, epileptic seizures, signs of neurological deterioration, particularly dementia and ataxia), suggestive of a progressive myoclonic epilepsy, that we propose to name senile progressive myoclonic epilepsy. Molecular studies are needed to characterize this syndrome from the physiopathological point of view.

p797 DOES PHOTOPAROXYSMAL EEG RESPONSE PREDICT SEIZURES CONTROL IN PATIENTS WITH JUVENILE MYOCLONIC EPILEPSY? M. P. Borkovic, and J. B. Jancic Clinic of Neurology and Psychiatry for Children and Youth, Belgrade, Serbia
Purpose: To evaluate does photoparoxysmal EEG response (PPR) predicts seizures control in patients with juvenile myoclonic epilepsy (JME). Method: Retrospectively we analyzed 109 patients with JME diagnosed and treated in period of 20022010 at Clinic of Neurology and Psychiatry for Children and Youth. PPR was defined by Waltz criteria during standard intermittent photic stimulation (IPS), and classified in four types. Result: We analyzed 109 patients with JME aged 12 - 39 years, mean old 20.1 years (SD -5.2 years), 65 (59.6%) females and 44 (40.4%) males. PPR was detected in 50 patients (29 females, 21 males). Waltz type IV (PPRs) was detected in 39 (23 females), and type III in 11 (6 females) patients. Forty one patients (82%) were photosensitive at flash frequencies between 10 and 30. In patients with PPR three patients had poor seizure control (six in group without PPR). Conclusion: PPR is most frequent in JME females. PPR type IV is most frequent in both genders. There is no difference in seizure control between patients with and without PPR. True prevalence of PPR in JME is difficult to evaluate because of the different definitions of PPR and the different protocols used for IPS .
p796 IDIOPATHIC OCCIPITAL LOBE EPILEPSY AND ABSENCE EPILEPSY IN THE SAME PATIENT? H. P. Grebe, and A. Ferreira Centro Hospitalar de Entre Douro e Vouga, Hospital So Sebastio, Santa Maria da Feira, Portugal
Purpose: Gastaut type occipital lobe epilepsy of infancy is a rare condition. Seizures typically consist of visual hallucinations, blindness or both, with or without motor manifestations. In some cases, additional atypical absence seizures have been described. On the other hand, aura phenom-
p798 NOCTURNAL FRONTAL LOBE EPILEPSY AND PARASOMNIAS DIFFERENTIAL DIAGNOSIS: ACCURACY OF TWO DIFFERENT CLINICAL DIAGNOSTIC TOOLS M. Broli*, F. Bisulli, L. Di Vito, C. Leta, B. Mostacci, I. Naldi, P. Tinuper, and L. Vignatelli *IRCCS, Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna, Universit di Bologna, Bologna, Italy; and City of Bologna Local Health Trust, Bologna
232 Abstracts
Purpose: To explore the diagnostic performance of two different tools for the nocturnal frontal lobe epilepsy (NFLE) and parasomnias differential diagnosis: Frontal Lobe Epilepsy and Parasomnias Scale (FLEP scale) and structured interview for nocturnal frontal lobe epilepsy (SINFLE). In fact the standard criteria for nocturnal episodes are unreliable or are still lacking. Method: 35 subjects with suspected NFLE or parasomnias, have been referred to our Sleep Epilepsy Center during the last three years. According to anamnestic, clinical and instrumental (EEG, home-video and video-EEG polysomnography, VEPSG) data 19 subjects were diagnosed as NFLE, 8 as parasomnias and 8 as uncertain diagnosis. After at least six months follow-up, all patients were re-evaluated through the FLEP scale and SINFLE, telephonically administered by a neurologist blinded to the initial diagnosis. Result: The FLEP data were in agreement with the first diagnosis for 15/19 NFLE and for 5/8 parasomnias; the SINFLE data were in agreement with the first diagnosis for 12/19 NFLE and for 6/8 parasomnias; both tools agreed with final diagnosis in judging uncertain patients. Conclusion: FLEP scale and SINFLE showed a similar diagnostic performance in the NFLE and parasomnias cases, so an assessment of the likelihood of epilepsy may be made at the initial consultation, even when the clinician has limited experience with these conditions, suggesting or avoiding a VEPSG. Purpose: Progressive myoclonic epilepsy (PME) is a rare and heterogeneous syndrome with various genetic etiologies. Therefore genetic studies carry an important role in the diagnosis. However the underlying mechanism of this syndrome is not understood. We aimed to determine the the clinical, genetic and EEG characteristics of Turkish PME patients. Method: In this study, 16 (11 male, 5 female) consecutive PME patients were investigated. Characteristics of disease progression and dependency in daily life activities were evaluated. Nine of the PME patients belong to three families, and the remaining 7 patients were sporadic. The mean age of patients was 3712 years (1964) at the examination. The mean age at the onset of illness was 155 years (321). The mean follow-up period was 116 years (range: 221). Result: We noticed a slow clinical progression in 2/3 of the patients interestingly and observed that similar baseline EEG abnormalities were continuing on EEG follow ups after years, without severe and worsening impairment of background activity. Seven patients showed photosensitivity, four of them were sensitive to lower stimulation frequencies. Genetic analysis showed variants in 3rd exon of EPM2A gene in 2 subjects and in 1st exon of NHLRC1 gene in one patient, which were not reported previously. None of the previously reported mutations were detected in our cohort except known polymorphisms which do not cause aminoacid changes. Conclusion: This study showed better prognosis than expected in Turkish familial and sporadic PME cases. Presence of new genetic variations can be speculated as the main reason of this slow progression.
p799 FOCAL EEG ABNORMALITIES IN CHILDHOOD ABSENCE EPILEPSY ANY PROGNOSTIC VALUE? M. Mazurkiewicz-Beldzinska, A. Matheisel, and M. Szmuda Medical University of Gdansk, Gdansk, Poland
Purpose: Childhood Absence Epilepsy is an Idiopathic Generalized Epilepsy (IGE) syndrome characterized by typical absence seizures (TAS). In last years it becomes more and more evident that focal EEG changes can be detected in patients with CAE. In order to estimate the frequency of this changes and their possible prognostic value present study was undertaken. Method: Patients with childhood absence epilepsy (CAE) who were hospitalized or consulted at Dept. of Developmental Neurology between 2000 and 2011 were included in the study and followed prospectively. All patients underwent video-eeg monitoring at regular interwals (approx 6 months). Result: 197 patients who fulfilled criteria for CAE were included in the study. In 17% of them we found interictal focal epileptiform discharges, and in 37% intermittent temporal slow waves. We found significant correlation between presence of interictal focal epileptiform discharges and long term prognosis, but did not find the correlation between worse prognosis and presence of temporal interictal slow wave activity. However the strongest correlation was found between the absence of interictal changes and seizure freedom. We also did not found the association between the presence of interictal focal abnormalities and performance in cognitive tasks. Conclusion: The value of focal interictal EEG abnormalities should not be overestimated according to prognosis and cognitive performance in children with CAE.
p801 DELAYED DIAGNOSIS OF COELIAC DISEASE IN ADULT PATIENTS WITH POSTERIOR PARTIAL EPILEPSY: SEARCHING FOR A POSSIBLE LINK S. Casciato, A. Morano, J. Fattouch, L. Lapenta, M. Fanella, M. Manfredi, C. Di Bonaventura, and A. T. Giallonardo Policlinico Umberto I, Rome, Italy
Purpose: Coeliac disease (CD) is an immuno-mediated small bowel disease characterized by chronic inflammation in the small intestine wall in genetically susceptible population due to a permanent intolerance to gliadin. CD is characterized by malabsorption, intestinal mucosa atrophy and serological positivity to AGA, tTG, EMA antibodies. A variety of extra-intestinal symptoms has been recently reported even in patients without enteric manifestations. Several neurological complications have also been described, including epilepsy, whose evolution might improve thanks to a prompt diagnosis of CD and adequate glutenfree diet. Method: Our study retrospectively revised 21 subjects (17 females, 4 males) with posterior partial epilepsy. EEG, brain MRI/CT scan, serological tests for CD and duodenal biopsy have been collected, as well as data about response to antiepileptic drugs treatment and gluten-free diet Result: Diagnosis of epilepsy always preceded the detection of CD: serological tests for CD were positive in 17/21 patients; in the others duodenal biopsy was performed and CD confirmed. 18/21 patients presented with common ictal symptoms (visual manifestations, dizziness, confusion); in 17/21 cases the EEG showed focal posterior abnormalities; in 4/ 21 FOS phenomenon was observed. The neuroimaging studies documented occipital calcifications in 4/21 patients. Gluten-free diet led to a reduction of seizure frequency in half of patients. Conclusion: Posterior epilepsy and CD can coexist in adults. Posterior seizures could raise suspicion of CD. These patients might be drug-resistant and present specific EEG pattern, but often an apparently normal brain. The causal relationship between these two conditions remains incompletely understood.
p800 CLINICAL, GENETIC, AND EEG FEATURES OF TURKISH PROGRESSIVE MYOCLONIC EPILEPSY PATIENTS O. E. Ore*, N. Bebek, F. N. Tuncer, O. Ozdemir, B. Baykan, C. Gurses, S. U. Iseri, U. Ozbek, and A. Gokygt *Ozel Memorial Hizmet Hospital, Istanbul, Turkey; and Istanbul University Istanbul Medical Fakulty, Istanbul, Turkey
233 Abstracts
p802 AN EPILEPSY BEDSIDE DIAGNOSIS BY DOING LOGICAL TASK IN FORM AD HOC FULL-TEXT DATABASE OF WORKING KNOWLEDGE V. M. Andreev Moscow State Medical Stomatolgy University, Moscow, Russian Federation
Purpose: To test ad hoc full-text database by making diagnosis of epilepsy. Method: The woman age 25 years has been myoclonic seizures, ataxia, amblyopia, and eye fundus macular cherry-red spot. A diagnostic process was done logical task in form of text database of working knowledge. A logical task is comparing one item with another and to find the coincidence as logical intersection of a certain quality. One item was consisted from prominent seizure of myoclonus and the related sign as macular cherryred spot. This item belongs to the set of disorders taken from the Internet. Other items were consisted from signs as ataxia and amblyopia. The comparison between three items was found the coincidence as sialidosis. Result: We are diagnosed 113 patients, both genders, between aged 18 and 56 years. The disorders were various paroxysmal disorders, rare epileptic syndromes, convulsive psychogenic status epilepticus, non epileptic staring spells, confusional attacks, dissociative fuges, epileptic staring spells, and sleep-related non-epileptic myoclonus. There has been a ninety five per cent correct bedside diagnosis. Conclusion: Diagnosing paroxysmal disorders by doing logical task in form ad hoc full-text database is making provable bedside diagnosis. ble phenocopy in the affected cousin, this pedigree highlights the challenges of careful phenotyping. Genetic discovery of the underlying genetic alteration using novel technologies such as Massive Parallel Sequencing will provide the opportunity to unravel the underlying genetic alteration.
p804 SLC2A1 MUTATIONS ARE CAUSE OF INFANTILE DRUG RESISTANT SEIZURES AND PAROXYSMAL EXERCISE-INDUCED DYSKINESIA M. K. Jurek, D. Hoffman-Zacharska, M. Kruk, E. Szczepanik, M. Geremek, and A. Friedman Institute of Mother and Child, Warszawa, Poland
Purpose: Glucose transporter-1 deficiency syndrome is an autosomal dominat disorder caused by mutation in SLC2A1 gene in the majority of patients results in reduce glucose transport into the brain. Patients with GLUT1 deficiency syndrome represent wide clinical spectrum of symptoms such as infantile drud-resistant seizures, developmental delay, microcephaly, spasticity and dystonia. Our purpose was to establish whether SLC2A1 mutation are common in patients with GLUT1 deficiency syndrome and comparison the clinical picture with the context of causative mutation. Method: Genomic DNA was extracted from peripheral blood . Standard PCR amplification of SLC2A1 gene of all 10 exons was perform using previously published primers. The coding regions of SLC2A1 were sequenced. For patients withoy point mutation the presence of gene's deletion/duplication was analysed by MLPA (SALSA MLPA P138-B1 MRC Holland) additionally. Unreported new variant was verified in a panel of 200 control alleles. Result: Mutation analysis was performed for all patients with GLUT1 deficiency syndrome. We identified one already known mutation c.634C>T (p.R212C) in a patient with idiopathic generalized drug-resistant epilepsy and a novel variant c.275+3A>C in a patient with paroxysmal exercise-induced dyskinesia. The new variant was not not found in 100 normal control subjects. Conclusion: Recognizing glucose transporter-1 deficiency syndrome is very important, since the disorder can be treated with a ketogenic diet. In most cases the diet reduces the frequency of seizures and the severity of the movement disorder.
p803 AUTOSOMAL RECESSIVE PARTIAL EPILEPSY WITH INTELLECTUAL DISABILITY (ARPEID) A NOVEL EPILEPSY SYNDROME? Z. Afawi*, J. Abu-Rachma, S. Kivity, I. Blatt, and I. Helbig *Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Shfaram, Israel; Schneider Children's Medical Center of Israel, Petach Tikva, Israel; Sheba Medical Center, Tel Aviv, Israel; and Kiel, Germany
Purpose: Recessive epilepsies constitute a major source of genetic morbidity in seizure disorders in the Middle East. Careful clinical characterisation and thorough description of the epilepsy syndromes are the prerequisite for successful gene discovery. The purpose of this study was to describe the peculiar clinical features in two sisters from a consanguineous Arab family. Method: A consanguineous Arab family with two affected sisters and one affected cousin were characterized clinically and electroencephalographic and imaging data was reviewed. Result: Both sisters presented with a similar phenotype, including severe primary developmental delay, muscular hypotonia and intellectual disability. At the age of 3 years, both sisters developed a focal seizure disorder with complex partial seizures and bitemporal discharges on the EEG. While seizures in one sister improved over time and were well-controlled at the time of the last consultation, the seizures remained refractory in the other sister. An affected cousin presented with a much milder neurological phenotype. Hydrocephalus of possibly perinatal origin was noted, suggesting that the phenotype in the cousin may represent a phenocopy. Conclusion: Given the similar clinical features in both sisters, we hypothesize that the phenotype may represent a novel autosomal recessive epilepsy syndrome and we suggest the term Autosomal Recessive Partial Epilepsy with Intellectual Disability (ARPEID). Given the possi-
p805 MAGNETOENCEPHALOGRAPHY FINDINGS IN TWO CASES OF IDIOPATHIC GENERALIZED EPILEPSIES S. Carrasco Garca De Len*, M. Gudn RodriguezMagarios*, L. Burriel Lobo*, G. Niso Galan, and F. Maestu Unturbe *Hospital General Universitario De Ciudad Real (Spain), Ciudad Real, Spain; and Universidad Complutense De Madrid, Madrid, Spain
Purpose: Among others the three main syndromes of Idiopathic Generalized Epilepsies (IGE) consists of Juvenile myoclonic epilepsy (JME), juvenile absence epilepsy (JAE), and epilepsy with generalized tonic-clonic seizures on awakening. From a neurophysiological, neuropsychological and neuroimaging point of view these three entities have consistently pointed out towards subtle abnormalities in frontal lobes (Santiago 2002, Roebling 2009). Using magnetoencephalography (MEG) we investigated electromagnetic sources of epileptic activity in 2 patients with IGE. Method: We retrospectively compared MEG and EEG. Using 306channel helmet-shaped MEG with a sampling rate of 600 Hz. Single dipole analysis assuming a spherical head model was performed for localization.
234 Abstracts
Result: Case 1: 25 years old man with JME diagnosis by the age of 16 years. He was on remission for 3 years. MRI was normal. He showed an EEG recording normal. MEG detected spike and spike-wave localised at left fronto-parietal region. Case 2: 25 years old female with JME diagnosis by the age of 12 years. She was on remission for 4 years. MRI was normal. EEG recording: spikes and slow waves of polyspike, generalized, bilaterally symmetrical, 4 to 6 Hz. MEG analysis: polyspike generalized with predominance bilateral fronto-parietal lobes, the spikes were more frequent than in EEG Conclusion: In these two cases MEG has a higher sensitivity and spatial resolution than scalp EEG, therefore MEG could localize frontal epileptic source predominance, not clearly revealed by scalp EEG. Implication of the frontal and parietal areas it is suggested by MEG data, as the neuropsychological, neuroimaging and neurophysiology previous reports have previously pointed out. Purpose: ESES (epilepsy with electrical status during slow-wave sleep) is a childhood onset electroclinical syndrome. We found no earlier description of middle-age onset ESES. Method: The first author has followed the patient (born 1955) since 1981. EEG recordings (N=7) were evaluated according to the intensity of discharges. The Wechsler intelligence test (WAISS, N=4) served in assessing the developmental profile. Result: At the age of 8 months the patient was diagnosed as having cerebral palsy and epilepsy. He learned to speak fluently and walk with the help of a walking stick. He had mild intellectual disability. Brain MRI showed an almost missing right hemisphere with slight cortex along the skull; also the left thalamus was destroyed. Follow-up 1999: Yearly, the patient had 1 or 2 facial jerks. EEG showed left parietal foci. AED: phenytoin and clonazepam. 2003: The patient was seizure-free; but he slept a lot and had become apathetic and walking difficulties were obvious. The patient could not live alone anymore. 2005: The patient was aggressive and restless and kept on changing posture continuously. EEG showed ESES. AED: topiramate and phenytoin. 2006: The patient had several dog-seizures (panting like a dog and walking, tachykardia, sweating). 2009: Clobazam was started soon after that all dementia, psychotic and motor symptoms disappeared. 2012: The patient is seizure free and lives alone. EEG shows left parietal foci. AED: topiramate and clobazam. Conclusion: ESES is worth keeping in mind for an adult patient with structural brain abnormality and showing psychotic behavior and global functional decline.
p806 OUTCOME AND PROGNOSTIC FEATURES IN SCN1A POSITIVE DRAVET SYNDROME FROM INFANCY TO ADULT LIFE A. Brunklaus, R. Ellis, E. Reavey, G. Forbes, and S. M. Zuberi Royal Hospital for Sick Children, Glasgow, UK
Purpose: Dravet syndrome is a severe infantile onset epileptic encephalopathy associated with mutations in the SCN1A gene encoding the alpha subunit of the voltage gated sodium channel Nav1.1. To date no large studies have systematically examined the outcome and prognostic features of the disease. Method: We prospectively collected data on 241 SCN1A mutation positive Dravet syndrome cases aged 1 to 42 years over a five year period. From structured referral data we examined a range of clinical characteristics including epilepsy phenotype, seizure precipitants, vaccination history, EEG data, imaging studies, response to treatment, mutation class and neuro-cognitive sequelae. Predictors of developmental outcome were determined by logistic regression. Result: There was a significant increase in the degree of learning disability seen in the older age groups (X2=184.45, df=24, p<0.001). With advancing age we similarly observed a significant increase in autistic features (X2=39.53, df=6, p<0.001), behaviour problems (X2=54.05, df=6, p<0.001) and acquired motor disorder (X2=37.19, df=6, p<0.001). The presence of status epilepticus (OR=3.1; CI=1.56.3; p=0.003), motor disorder (OR=3.3; CI=1.76.4; p<0.001), interictal EEG abnormalities in the first year of life (OR=5.7; CI=1.916.8; p=0.002) and early cognitive impairment (OR=0.9; CI=0.940.99; p=0.009), each predicted a worse developmental outcome. No significant effect was seen for seizure precipitants, vaccination history, MRI abnormalities or mutation class (truncating vs. missense). Conclusion: The identification of factors influencing prognosis both aids counselling and encourages early, syndrome specific therapy. Prevention of status epilepticus with regular medication and emergency protocols is important and may influence developmental outcome.
p808 CAN NEONATAL ELECTROCLINICAL FINDINGS GUIDE TOWARDS AN EARLY DIAGNOSIS OF NEONATAL ENCEPHALOPATHY? A CASE REPORT B. Scelsa*, A. Peron*, L. Spaccini*, P. Introvini*, S. M. Bova*, R. Ciccone, F. Novara, O. Zuffardi, and M. Mastrangelo* *V. Buzzi Children's Hospital, Milano, Italy; and Universit Di Pavia, Pavia, Italy
Purpose: STXBP1 and SPTAN1 mutations are increasingly recognized as responsible of early infantile epileptic encephalopathies with an EEG pattern ranging from discontinuous to burst-suppression. The purpose of this case report is to emphasize the possibility that a condition of encephalopathy, associated to a peculiar EEG pattern can, be representative of specific genetic early- onset epileptic encephalopathies, despite the absence of epileptic seizures in the first month of life. Method: We describe a female born after a pregnancy characterized by polidramnios. Mild dysmorphic features, a severe swallowing defect and hypotonia were detected after birth. Result: Protracted video-EEG recordings in the neonatal period displayed an EEG pattern ranging from discontinuous to burst-suppression. MRI and metabolic investigations were unrevealing. At 2 months of life she developed West syndrome, rapidly controlled after Vigabatrin treatment. The EEG improved before the end of the first year of life to an unspecific slowing of background activity without epileptic abnormalities. Significant improvement of swallowing was apparent after 6 months of life, permitting an oral nutrition. The psychomotor development resulted severely affected. The interaction was limited and the language absent. Rotatory nystagmus was observed. Array-CGH detected a de novo deletion of 2.4 Mb in 9q34.11 involving both STXBP1 and SPTAN1 genes. Conclusion: Specific molecular genetic investigations should be included in the diagnostic work up of encephalopathic neonates presenting with a peculiar pathological EEG pattern (from severely discontinuous to burst-suppression) even in the absence of epileptic seizures.

p807 ESES (CSWSS) IN A MIDDLE-AGED MAN M. Arvio, O. Sauna-Aho, and T. Nyrke Lahti, Finland
235 Abstracts
p809 NEUROLOGICAL ACPECTS OF DIALYSIS PATIENTS S. M. Vujisic Clinical Centre of Montenegro, Podgorica, Montenegro
Purpose: Metabolic encephalopathies are defined as any patological process that damages the methabolism of the brain in significant matter and inevitably alter level of consciousness. Cognitive and emotional functions are amoung most complex brain activities, and therefore are most sensitive to toxic product retention and secondary metabolic changes. Method: Group of 36 patients who were on hemodyalises were examined. All of them were devided into two groups, group with normal, and group with abnormal EEG findings. All patients underwent neuropsychology and MMSE examination. Test achievements were scored as 25 and more for normal, and 24 or less for abnormal results. Result: In patients with abnormal results, who had MMSE done, regardless the changes found in EEG, no statistically significant differences were found among the group. Number of patients who had score 25 or more was the same compared with the number of patients who had score 24 or less (8 patients). In the first group with normal EEG, number of patients who had score 25 and more was 18 (90%), compared with 2 patients who had score 24 or less (10%). Comparing the results for doing MMSE, statistically significant difference was found among patients with normal EEG findings and patients with pathological EEG findings. Conclusion: Celebrovascular complications in these patients are amplified and lead to cognitive disfunction, that are subcortical by nature. These findings are in the corelation with findings of the others who studied the same pathology (Roman CG, 2003).
p811 EEG EVOLUTION IN CHILDREN WITH WEST SYNDROME D. M. Nikolic*, N. Dimitrijevic, D. Bogicevic, V. Mitic, B. P. Medjo, S. Puric, and I. Milovanovic* *Belgrade University Medical School, Belgrade, Serbia; and University Children's Hospital Belgrade, Belgrade, Serbia
Purpose: West syndrome (WS) is catastrophic epileptic encephalopathy with poor prognosis. The aim of the study was to determine the most frequent EEG pattern in patients with WS at the disease onset and during two year follow-up period. Method: Study group comprised 81 patients with WS whose EEG performed initially and after 3, 6, 12 and 24 months was analyzed. Result: In 67.9% of patients initial EEG showed hypsarrhythmic pattern, in 19.8% modified hypsarrhythmia, in 4.9% burst suppression pattern, in 4.9% focal and in 2.5% multifocal EEG findings. After 3 months improvement was observed in 56.2% of patients, unchanged findings in 34.2%, deterioration in 9.6% (p<0.01). The best outcome was found in patients with initial hypsarrhythmic pattern (63.8%) and somewhat worse in those with modified hypsarrhythmia (50%). Patients with burst suppression pattern and those with focal and/or multifocal EEG changes had the same or worse findings at all later check-ups. Trend of improvement was continued at later follow-ups: 6 (48.1%), 12 (55.4%) and 24 months (37.1%), while unchanged EEG findings were found in 44.4%, 36.5% and 53.2% of patients respectively. Worst EEG findings were recorded in 7.4%, 8.1%, and 37.1% of patients after 6, 12 and 24 months respectively. Conclusion: Stabilization of EEG 3 months after disease onset was favourable indicator and has its clinical significance for seizure control and psychomotor development.
p810 NEUROPSYCHOLOGICAL ASPECTS OF DIALYSIS PATIENTS D. B. Milikic, L. B. Radulovic, S. M. Vujisic, and S. Vujovic Clinical centre of Montenegro, Podgorica, Montenegro
Purpose: Influence of toxic renal products on cognitive function in patients on dialysis. Metabolic encephalopathies are defined as any pathological process that damages the metabolism of the brain in significant matter and inevitably alter level of consciousness. Method: Group of 36 patients who were on hemodialysis were examined. All of them were devided into two groups, group with normal and group with abnormal EEG findings. All patients underwent neuropsychiatry and MMSE examination. Test achievements were scored as 25 and more for normal, and 24 or less for abnormal result. Result: In patients with abnormal results, who had MMSE done, regardelees the changes found in EEG, no statistically significant diferencess were found amoung the group. Number of patients who had score 25 or more was the same compared with the number of patients who had score 24 or less (8 patients). In the first group with normal EEG, number of patients who had score 25 and more was 18 (90%), compared with 2 patients who had score 24 or less (10%) Comparing the results found doing MMSE, stastistically significant diference was found amoung patients with normal EEG findings and patients with patological EEG findings. Conclusion: Cerebrovascular complications in these patients are amplified and lead to cognitive disfunction, that are subcortical by nature. These findings are in the correlation with findings of the others who studied the same pathology (Roman CG, 2003).
p812 SEVERE PATTERN-SENSITIVITY IN A GIRL WITH DRAVET SYNDROME, DUE TO MICRODELETION IN LOCUS 2Q24.3. A CASE REPORT E. Szczepanik, D. Hoffman-Zacharska, A. Jeziorek Anetta, I. Terczynska, and J. Bal Institute of Mother and Child, Warsaw, Poland
Purpose: To report on 5.5 year-old-girl with Dravet syndrome and with severe pattern-sensitivity Method: Clinical, EEG and genetic data were analyzed Result: The patient was a healthy female born at term. Her maternal grandmother suffered from epilepsy considered as postraumatic. At the age of 4 months she had her first febrile seizure as cluster of myoclonias lasting 40 minutes. Since 11 months of age she developed both febrile and afebrile seizures of different types encompassing GTCSs, myoclonias, absences, focal seizures, and a few status epilepticus. Parents noticed that most seizures occurred while watching almost any strip patterns. EEG showed brief generalized spike-waves, polyspikes-waves paroxysms and focal spikes as well, with IV grade photosensivity and photoconvulsive response. MRI/ MRS of brain were normal. Dravet syndrome was suspected and molecular analysis of the SCN1A gene performed. Genetic testing revealed on point mutations in the SCN1A coding sequence, but deletion of the size 1.5Mb on the one chromosome 2, in locus 2q24.3, encompassing the whole SCN1A gene and six additional, of which SCN9A may act as phenotype modifier. The patient was treated with many AEDs without effect. Stiripentol was added to VPA and clobazam at the age of 4 years, and she has had two febrile GTCSs since then. Her cognitive development has slown down, however it is still within normal range, but she exibits mild cerebellum ataxia. Conclusion: Such extensive mutation of SCN1A gene might be considered as important cause of such severe photosensitivity in our patient.
236 Abstracts
p813 NEONATAL CEREBRAL SINOVENOUS THROMBOSIS (CSVT) WITH THALAMIC HAEMORRHAGE IS STRONGLY RELATED TO ELECTRICAL STATUS EPILEPTICUS IN SLEEP (ESES) F. E. Jansen*, K. Kersbergen, K. P. J. Braun, F. S. S. Leijten, R. J. Nievelstein*, F. Groenendaal, M. Benders, and L. S. De Vries *University Medical Center Utrecht, Utrecht, The Netherlands; UMC, Utrecht, The Netherlands; Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands; UMC Utrecht, Utrecht, The Netherlands; and Wilhelmina Children's Hospital, Utrecht, The Netherlands
Purpose: To assess the prevalence of electrical status epilepticus in sleep (ESES) and postneonatal epilepsy after neonatal cerebral sinovenous thrombosis (CSVT) associated with a thalamic haemorrhage. Method: We included thirteen children (age 28 years) diagnosed, between 2003 and 2008, with neonatal CSVT, and an associated thalamic haemorrhage (assessed on MRI), in the University Medical Center Utrecht, the Netherlands. Neurodevelopment and seizures history were routinely followed up in the outpatient clinic. Sleep EEG recordings were performed to assess the prevalence of ESES; defined as a spike wave index (SWI) exceeding 60%, and confirm the diagnosis of epilepsy. Result: Four children were diagnosed with ESES syndrome. Three presented with seizures, and one showed inattentiveness, suspected of absences. Sleep induced epileptiform activity < 60% (ESES spectrum) was seen in two children, of whom one had seizures and the other a learning disability. Three children were diagnosed with focal epilepsy with partial seizures, in the absence of ESES. Of the four with a normal EEG, one had a global developmental delay. Two of the 13 children had developed a mild hemiplegia. Conclusion: Neonates with a thalamic haemorrhage, associated with a straight sinus thrombosis, are at high risk of developing ESES (spectrum) syndrome (46%) and focal epilepsy (31%). Electrographical findings were already present at a young age, in some cases even before cognitive deficits were recognised. Early diagnosis and subsequent treatment may prevent cognitive deterioration. Routine annual sleep EEG recordings are recommended in children with neonatal thalamic injury. Result: We identified 7 unrelated children (6 females, 1 male) with STXBP1 mutations. Age at seizure ranged from 1 day to 3 months. All children presented with IS and 5 had a suppression-burst pattern on EEG. Although all patients were seizure free on AEDs by the age of 2 years, they showed global and severe developmental delay. Neuroimaging analysis showed a peculiar aspect of slight and dysmorphic corpus callosum (6/7 patients) associated with cortical frontal atrophy (4/7 patients). Conclusion: STXBP1 mutations are detected only in a minority of patients with early epileptic encephalopathy. We suggest with thin and dysmorphic corpus callosum and frontal cortical hypoplasia on brain MRI, especially if seizures are controlled in the first years, could represent the best candidates to genetic analysis of STXBP1.
p815 A ROLE FOR THE CXCR3/CXCL10 AXIS IN RASMUSSEN ENCEPHALITIS. A NEW TARGET FOR IMMUNOTHERAPHY? M. Prez-Jimnez*, I. De Prada*, I. Mirones, A. Gmez*, A. Luque*, R. Martn*, F. Villarejo*, J. Garca-Castro, L. Madero*, and M. Ramirez Orellana* *Hospital Infantil Universitario Nio Jess, Madrid, Spain; and Instituto De Salud Carlos Iii, Madrid, Spain
Purpose: Previous studies suggest that the effector lymphocytes responsible for the brain destruction in Rasmussen Encephalitis (RE) migrate from the periphery to the cerebral parenchyma, where they cause the damage. The purpose of our study was to gain information about the molecular basis of the recruitment of T lymphocytes from the periphery to the areas of brain destruction in patients with RE. Method: We have studied the implication of CXCL10-CXCR3 in RE, a chemotactic axis involved in the pathogenesis of several cases of immune encephalitis, by analysisng pathological specimens of 6 children with RE and by functional in vitro assays. Result: We found that cytotoxic T lymphocytes infiltrating the damaged areas of primary biopsies expressed CXCR3, while neurons and astrocytes in the same areas expressed CXCL10. In in vitro assays, we found that astrocytes upregulated the expression of CXCL10 mRNA, and the release of CXCL10 to the supernatants, upon stimulation with Polyinosinic-polycytidylic acid (Poly (I:C), a synthetic dsRNA which mimics infections with either RNA or DNA viruses. Activated T lymphocytes responded to the production of CXCL10 by Poly (I:C)-stimulated astrocytes by increasing their migration in a transwell assay. Finally, the chemotaxis induced by the stimulated astrocytes was completely abrogated in the presence of small molecules antagonists of CXCR3. Conclusion: Our results show that the CXCR3-CXCL10 axis has a role in recruiting pathogenic T lymphocytes into the brains of RE patients, and that this finding may be targeted pharmacologically.
p814 EARLY EPILEPTIC ENCEPHALOPATHIES ASSOCIATED WITH STXBP1 MUTATIONS: COULD WE BETTER DEFINE THE PHENOTYPE? G. Barcia*, N. Chemaly*, S. Gobin*, M. Milh, P. Van Bogaert, C. Barnerias*, A. Kaminska*, O. Dulac*, V. Cormier*, N. Boddaert*, and R. Nabbout* *Hopital Necker Enfants Malades, Paris, France; Hopital La Timone, Marseille, France; and Hopital Erasme, Bruxelles, Belgium
Purpose: STXBP1 (MUNC18.1), encoding syntaxin binding protein 1, is a new gene causing early epileptic encephalopathy. Heterozygous mutation in STXBP1 have first been reported in Ohtahara syndrome (EOEE) (Saitso et al., 2008), then in patients affected by infantile spasms (IS) (Otsuka et al., 2010) and, more recently, in patients with non syndromic mental retardation without epilepsy (Hamdan et al., 2011). To better define the clinical phenotype and to determine the occurrence of specific neuroradiological abnormalities in patients with STXBP1 mutations, we analyzed clinical and neuroradiological findings in a series of patients having STXBP1 mutations Method: We included patients with STXBP1 abnormalities followed at our institutions and who underwent a high resolution brain MRI.
p816 ABSENCE OF THALAMIC METABOLIC CHANGE IN EPILEPSIES WITH CONTINUOUS SPIKE-WAVES DURING SLEEP N. Ligot*, F. Archambaud, N. Trotta*, S. Goldman*, P. Van Bogaert*, C. Chiron, and X. De Tiege* *Universit Libre de Bruxelles, Brussels, Belgium; and Inserm, Paris, France
Purpose: Some evidence suggests that the thalamus might play a key role in the pathophysiology of epileptic encephalopathies with continuous spike-waves during sleep (CSWS). Previous studies investigating regional metabolic changes associated with CSWS activity compared the
237 Abstracts
brain metabolism of children with CSWS with that of healthy adults, precluding any assessment in brain areas showing physiologic age-related metabolic changes such as the thalamus. Method: Positron emission tomography using [18F]-fluorodeoxyglucose (FDG-PET) was performed in 15 children at the acute phase of CSWS (3 girls, age: 5 to 11 years). Voxel-based analyses identified significant metabolic changes in patients compared to a paediatric control group (12 girls and 6 boys, age: 6 to 11.5 years, focal cryptogenic epilepsy with normal FDG-PET) using SPM8. Age-related metabolic changes were identified by comparison of FDG-PET data obtained in patients, paediatric controls and healthy adults (15 women, age: 18 to 51 years). Result: Hypermetabolism in centro-temporal regions bilaterally and hypometabolism in the prefrontal cortex, the precuneus, the posterior cingulate cortex and parahippocampal gyri characterized the acute phase of CSWS (p inf. 0.05, FWE). Although highly significant thalamic hypometabolism was found in both paediatric populations compared to adults, no change in this sub-cortical structure was found in patients compared to paediatric controls, even at very low threshold (p inf. 0.05 uncorrected). Conclusion: This study suggests that CSWS is not associated with sustained changes in thalamic metabolism. These data further demonstrate that CSWS activity is associated with hypermetabolism at the site of the epileptic focus and hypometabolism in remote cortical areas.
p818 A SLC2A1 MUTATION IN A BOY WITH CHILDHOOD ABSENCE EPILEPSY, ALTERNATING HEMIPLEGIA AND ATAXIA H. Muhle, F. Mller, U. Stephani, and I. Helbig University Medical Center Schleswig-Holstein, Kiel, Germany
Purpose: Mutations in SLC2A1 (solute carrier family 2, member 1) cause a broad range of neurological disorders. Main features are movement disorders and childhood epilepsies, especially early onset absence epilepsy. The role of SLC2A1 in childhood and juvenile absence epilepsies, however, seems to be less important. Here we describe a patient with the rare combination of childhood absence epilepsy (CAE), alternating hemiplegia and mild ataxia. Method: The clinical course of a patient with CAE and additional neurological features is described. Analysis of SLC2A1 was performed using Sanger sequencing. Result: The boy was affected by left-sided hemiplegia and aphasia at the age of 6 years lasting for two hours. MRI and EEG were unremarkable. 9 months later, a second period of right-sided hemiplegia with aphasia was observed. EEG showed 3 Hz spike-wave paroxysms lasting for 4 seconds, accompanied by previously unnoticed loss of consciousness consistent with CAE. Mild ataxia was observed on neurological examination. The boy became seizure-free with valproate monotherapy. A pathogenic mutation in SLC2A1 was identified (c.274 C>T, p.Arg92Trp). Conclusion: The occurrence of SLC2A1 mutations in patients with CAE and alternating hemiplegia is unusual and our patient further expands the spectrum of GLUT1 deficiencies. GLUT1 mutations should be considered as an underlying cause when CAE coexists with additional neurologic features.

p817 PERSISTENT CONNECTIVITY DURING AWAKE AND SLEEP OF BRAIN LOCATIONS GENERATING CONTINUOUS SPIKE AND WAVES DURING SLOW SLEEP (CSWS) P. G. Larsson*, M. L. Stavrinou, D. Kugiumtzis, and J. F. Storm *Oslo University Hospital, Nydalen, Norway; University of Oslo, Oslo, Norway; and Aristotle University of Thessaloniki, Thessaloniki, Greece
Purpose: Continuous spike and waves during slow sleep (CSWS) is a condition encountered in children with epileptiform activity seen in their sleep Electroencephalograms. Various neuropsychological impairments are often seen in children with CSWS, like language, speech and learning disabilities or general cognitive deterioration. The mechanisms of this epileptiform-related cognitive dysfunction are poorly understood. The aim of this study was to evaluate brain connectivity patterns during awake and sleep in children with CSWS without any other epileptic pathology. Method: 24-hour electroencephalographic recordings of 10 children admitted to the National hospital in Oslo were analyzed using different connectivity methods: correlation, partial correlation and Directed Transfer Function. Result: Our results showed that the areas that generate this spike activity continue to participate in brain networks also during wakefulness and not only during sleep when this activity is maximal. The strength of connections and the appearance rate in brain networks did differ significantly between sleep and wakefulness. Conclusion: This persistent participation of spiking locations also during wakefulness is possibly causing functional changes to the normal brain connectivity patterns. This finding may help explain why cognitive deterioration occurs in children with CSWS.
p819 EYELID MYOCLONIA WITH ABSENCES (JEAVONS SYNDROME): A LIFE LONG DISORDER WITH MILD COGNITIVE IMPAIRMENT? H. T. Ong*, and K. J. Lim *National University Hospital, National University Health System, Singapore, Singapore; and Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Purpose: Following clear clinical description of eyelid myoclonia with absence (EMA) by Jeavons in 1977, several authors have reported similar patients. However, EMA has not yet been recognized as a distinct epileptic syndrome by the ILAE. The treatment response, possibility of long term remission and the association if any of cognitive impairment, is still poorly understood Method: We retrospectively reviewed children with EMA in our EEG database. These are neurologically normal children who had clinical presentation of eyelid myoclonia with absences. The diagnosis was confirmed by the presence of 36 Hz generalized spike-waves or polyspikewaves, with ictal manifestation of eyelid myoclonia and absence, proven on simultaneous video-EEG Result: Two girls fulfilled the diagnosis of EMA. The onset of seizures was at 2.5 years and 7 years respectively. Seizure control was achieved with valproic acid (VPA) monotherapy. The first patient remained seizure-free for 3 years with seizure recurrence 9 months after weaning off VPA. The second patient had seizure recurrence when she was briefly non-complaint after remaining seizure-free for 2 years whilst on VPA. Although both girls had normal developmental milestones in early childhood, their academic performances were below average when compared to their peers in school. The clinical features and EEG findings in our
238 Abstracts
patients with EMA are similar to those reported worldwide. Although seizure-free remission is easily achieved with VPA and sustained for 2 to 3 years, seizure recurrence is likely when VPA is weaned off or stopped. Our patients also had below average academic performance in school. Conclusion: Epilepsy surgery is promising for seizure control and improvements of QOL, MQ and IQ in carefully selected SAC with intractable partial epilepsy, the surgical outcomes in China were not less than the data from developed countries. Early surgery should be taken into consideration in SAC with focal lesions. School-age children with lowIQ and generalized epileptiform discharge could not be excluded from resective epilepsy surgery.
p820 RESULTS OF THE STUDY OF HORMONES IN BLOOD OF GIRLS WITH EPILEPSY V. I. Guzeva, and V. V. Guzeva Saint-Petersburg Pediatric Medical Academy, Saint-Petersburg, Russian Federation
Purpose: Investigation of thyroid, parathyroid and adrenal hormones in blood of girls with epilepsy Method: Investigation of thyroid hormones thyrotropin, antibodes to thyroglobulin, triiodthyronine, thyroxine, parathyroid hormone and cortisol in blood of 50 girls with epilepsy and 47 of control group in the age groups 89, 1011, 1213, 1415 and 1617 years was conducted. Result: Investigation of changes in hormone levels in blood of girls with epilepsy and control group according to age revealed that girls with epilepsy 89, 1011, 1213, 1415 and 1617 years in most cases (86.67%) had levels of these hormones in blood higher than the control group of girls the same age. In 30% of cases the content of hormones in blood of girls with epilepsy was significantly higher (p 0.90), than in control group. In blood of girls with epilepsy 1617 years levels of all hormones exceeded those in blood of control group, and for triiodthyronine, cortisol and parathyroid hormone the difference was significant (p 0.90), while in blood of girls 1415 years significant difference was found for triiodthyronine and cortisol, in blood of girls 1213 years- for thyrotropin, 10 11 years- for cortisol, 89 years- for thyrotropin and cortisol. Significant reduction in level of hormones in blood of girls with epilepsy compared with control group in subgroups 89, 1011, 1213, 1415 and 1617 years were not found. Conclusion: So, the content of cortisol in blood of girls with epilepsy was significantly higher in all age groups except for 1213 years.
p822 DETECTION OF EPILEPTIC SEIZURE IN CHILDREN USING NON-LINEAR ANALYSIS IS HRV V. Kharytonov*, I. Chaikovsky, V. Bukhman, Y. Frolov, and V. Mishiev* *Kyiv's Municipal Psycho-Neurological Hospital #1, Kiev, Ukraine; International Research and Training Center of NAS of Ukraine, Kiev, Ukraine; and Biosignal Consulting, New York, IL, USA
Purpose: It is known fact that during epilepsy seizure HR significantly increases. It also affects HRV. We hypothesized that changes of non-linear parameter SampEn may indicate ictal period of epilepsy seizure more precisely then HR changes. Method: Patients group: 24 patients (12 boys, 12 girls), age 2m 25years (mean 7.1 y) All the patients underwent vEEGmonitoring with polisomnography for 12 hours with detection of paroxysmal events of various etiology. Focal seizures: 11 patients Generalised seizures: 6 patients Control group of 7 patients with nonepileptic paroxysms In addition to HR, Sample Entropy as a measurement of complexity of time series of RR intervals, {RR1, RR2, RR3, RRiRRn was calculated. Genetic algorithm was used to define the threshold value of these two parameters. Result: In group with focal seaizures, sensitivity of seizure detection by SampEn was 100%, by HR 78%, specificity 96% and 70% respectively. In group with generalized seizure accuracy of seizures detection by SampEn was significantly lower and comparable with accuracy of seizure detection using HR. Conclusion: Non-linear analysis of HRV is more accurate then HR changes in epileptic seizure detection in patients with focal seizures. Further research needed to confirm these findings
p821 LONG TERM OUTCOMES OF EPILEPSY SURGERY IN SCHOOL-AGE CHILDREN WITH PARTIAL EPILEPSY S. Liang, Z. Zhang, and X. Hu First Affiliated Hospital of PLA General Hospital, Beijing, China
Purpose: To compare surgical outcomes of school age children (SAC) with intractable partial epilepsy from China and those from developed countries, and introduce surgical candidate selection. Method: We retrospectively selected 206 SAC aged 614 years with epilepsy surgery in our center from Sep., 2001 to Jan., 2007. We analyzed patient's general clinical features, examinations, treatments, and surgical outcomes, including seizure control at 1 year follow-up (1FU), 3 years (3FU) and 5 yrs (5FU) after operation, and changes of intelligence quotient (IQ), memory quotient (MQ) and QOL from preoperative to 2FU. Also, the effects of surgical outcomes were analyzed. Result: Postoperative seizure freedom was rendered in 173 cases (84.0%) at 1FU, 149 (72.3%) at 2FU, and 139(67.5%) at 5FU, and patients with focal MRI abnormalities and short history of seizure were likely to obtain postoperative seizure free. patients with preoperative low-IQ and children with seizure free rendered full MQ, IQ and overall QOL improvement at 2FU, and the significant differences were found in the mean changes of full IQ, full MQ, overall QOL between patients with preoperative low-IQ and corpus callosotomy and those with normal IQ, and between children with seizure free and those with continual seizure attack.
p823 THE SPECTRUM OF BENIGN INFANTILE SEIZURES INCLUDING BENIGN INFANTILE SEIZURES WITH MILD GASTROENTERITIS, BENIGN INFANTILE FOCAL EPILEPSY WITH MIDLINE SPIKES AND WAVES DURING SLEEP AND OTHERS I. Y. Saadeldin Tawam Hospital, Al Ain, United Arab Emirates
Purpose: To highlight the characteristic features of Benign Infantile Seizures and demonstrate the benign nature of the syndrome. The syndrome includes many new entities. The aim of this review is to describe these entities, discuss their nosological aspects, compare our results with the international studies and demonstrate by videos the characteristic electroclinical features. Method: Two studies were performed: 1. A case series of 275 patients with epileptic seizures who fulfilled the criteria of BIS were followed over a period of 3 years and 7 months which included patients with paroxysmal dyskinesia2. Twenty-five patients who fulfilled the diagnostic criteria for benign infantile seizures with mild gastroenteritis were assessed and followed between January 2004 and January 2009.
239 Abstracts
Result: In 2009, Saadeldin et al. documented for the first time the presence of benign infantile seizures (Fukuyama-WatanabeVigevano syndrome) in Saudi Arabian and Arab populations. The authors highlighted the characteristic features of BIS and demonstrated the benign nature of the syndrome. One year later, Saadeldin analyzed the electroclinical features of patients with benign infantile seizures with mild gastroenteritis (BIS with MG) and demonstrated the benign nature of this entity. Conclusion: Increasing the awareness of clinicians regarding the existence of these syndromes and their benign nature in children will limit unnecessary investigations. lished. During intracerebral bleeding blood constituents enter the neuronal tissue and produce both an acute and delayed effect on brain functioning. Among the blood components only thrombin has been shown to evoke seizures immediately after entering brain tissue. In the present study we tested the hypothesis that thrombin increase neuronal excitability in the immature brain through alteration of voltage-gated sodium channels. Method: The thrombin effect on neuronal excitability and voltage-gated sodium channels was assessed using extracellular and intracellular recording techniques in the hippocampal slice preparation of immature rats. Result: We show that thrombin increased neuronal excitability in the immature hippocampus in an NMDA-independent manner. Application of thrombin did not alter transient voltage-gated sodium channels and action potential threshold. However thrombin significantly depolarized the membrane potential and produced a hyperpolarizing shift of TTX sensitive persistent voltage-gated sodium channel activation. This effect of thrombin was attenuated by application of protease-activated receptor1 and protein kinase C antagonists. Conclusion: Our data indicates that thrombin amplifies of the persistent voltage-gated sodium current affecting resting membrane potential and seizure threshold at the network level. Our results provide a novel explanation as to how ICH in newborns results in seizures, which may provide avenues for therapeutic intervention in the prevention of post-ICH seizures.
p824 POTENTIALLY SEIZURE PROVOKING VIDEO SEQUENCES IN SPANISH TV: THE SMOKING GUN J. Parra*, B. Anciones*, M. Hodgetts, D. Jackson, and G. F. Harding *Hospital de La Zarzuela y Ntra Seora del Rosario, Madrid, Spain; Cambridge Research Systems Ltd, Rochester, Kent, UK; and ElectroDiagnostic Centre, Greenfields, Worcester, UK
Purpose: To analyse systematically the content of potentially seizure provoking video sequences from different Spanish television broadcasters checking for compliance with current guidelines in other countries. One in 4000 subjects is at risk of having a seizure when confronted with certain visual stimuli, often without being aware of their condition. Television is the most common cause of photosensitive seizures in the western world, but only the UK and Japan have adopted guidelines to prevent the broadcasting of video sequences that could potentially trigger seizures in susceptible people. Method: Television programs of all 5 national broadcasters available via Digital Terrestrial Television were recorded between 8 AM and 12 PM on 5 consecutive days, from January 1st 2012 through January 6th 2012. In addition, a channel with programming dedicated to children and a musical channel were also recorded. The video content was analysed using a HardingFPA Flash and Pattern Analyser (Cambridge Research systems) for compliance with the UK Ofcom guidelines. Result: We analysed 105 hours of television programs. We found 738 incidents that violated the guidelines (mean 105.43, CI95% 58.74 151.12), mostly luminance flashing (714 incidents, mean 102, CI95% 55.83148.17). Thirteen incidents involved spatial patterns and 11 red flashing. Forty-seven additional incidents considered dangerous were detected which, although technically meeting guidelines, continued for an extended period of time and were considered dangerous. Conclusion: Spanish broadcasters seem to be unaware of the risk of photosensitive epilepsy. National Guidelines should be adopted to lower the risk of Spanish TV content triggering epileptic seizures in susceptible viewers.

p826 PARTIAL POSTERIOR EPILEPSIES WITH PERSISTENT FIXATION OFF SENSITIVITY IN ADULT LIFE: ELECTRO-CLINICAL EVALUATION, NEUROIMAGING FEATURES AND EPILEPTIC SYNDROME DEFINITION J. Fattouch, A. Morano, A. T. Giallonardo, L. Lapenta, S. Casciato, M. Fanella, M. Manfredi, and C. Di Bonaventura Policlinico Umberto I, Rome, Italy
Purpose: The term Fixation of Sensitivity (FOS) was proposed by Panayiotopoulos to describe epilepsy/EEG change evocated by the suppression of central vision and fixation. The EEG pattern usually consists of spike/polyspike and waves localized in occipital regions. FOS occurs mainly in children with idiopathic occipital partial epilepsies and rarely in adults. In this retrospective study we evaluated clinical data/EEG/MRI findings of 15 epileptic patients with FOS persisting in adult life to better define the spectrum of syndromes. Method: We selected 15 consecutive patients (12 females/3 males; age range: 1959 years). The main inclusion criterion was the diagnosis of epilepsy with FOS persisting in adult life. We retrospectively analyzed clinical/EEG/ neuroimaging data. Result: We observed a female prevalence (F/M=12/3). 8 patients presented both simple and complex partial seizures whereas 7 had only complex seizures. Partial seizures evolved into generalized in 9 cases. The FOS pattern consisted of spike-and-wave and slow-wave abnormalities with a posterior localization (bilateral in 9/monolateral in 6). We recorded seizures in 10/15 patients. All showed a posterior onset (bilateral in 2/left in 2/right in 6). FOS was prevalent in symptomatic epilepsy (cortical malformations in 7; coeliac disease in 3; vascular malformation in 1; calcifications in 1). One patient presented a probably symptomatic epilepsy and only 2 an idiopathic syndrome (Gastaut syndrome).
p825 THROMBIN FACILITATES SEIZURES THROUGH ACTIVATION OF NEURONAL PERSISTENT SODIUM CURRENT: A NEW MECHANISM OF SEIZURE DEVELOPED DURING INTRACEREBRAL HEMORRHAGE O. Isaeva*, A. Hernan, D. Isaev*, and G. L. Holmes *Bogomoletz Institute of Physiology, Kiev, Ukraine; and Dartmouth Medical School, Lebanon, NH, USA
Purpose: An epileptic seizure is frequently the presenting sign of intracerebral hemorrhage (ICH) caused by stroke, head trauma, hypertension and a wide spectrum of disorders. However the cellular mechanisms responsible for occurrence of seizures during ICH have not been estab-
240 Abstracts
Conclusion: FOS can be observed in adult life in idiopathic epilepsy, representing the prolongation of the same phenomenon arisen during childhood. Nevertheless, it often represents the EEG expression of symptomatic epilepsies (cortical malformations/coeliac disease). bolic disorders, celiac disease). Forty-seven patients were not classified, in spite of several investigations. We performed a tentative sub classification of these patients, based on details of phenotypic presentation (onset age, presence of relevant cognitive decline, seizure frequency and associated neurological signs). Conclusion: This study is expected to support further genetic studies suitable to detect new diseases giving rise to the PME phenotype.
p827 DISTRIBUTION OF PROGRESSIVE MYOCLONUS EPILEPSIES IN ITALY; POSITIVELY DIAGNOSED AND UNCLASSIFIED PATIENTS L. Canafoglia*, S. Franceschetti*, R. Michelucci, A. Magaudda, G. Rubboli, P. Tinuper, P. Striano, S. Striano**, A. Gambardella, A. La Neve, T. Francavilla, E. Ferlazzo, D. Italiano, G. Gobbi, F. Villani*, N. Nardocci*, T. Granata***, P. Veggiotti, D. Pareyson*, G. Coppola, G. Uziel***, V. Belcastro, F. Bisulli, R. Spreafico, R. Guerrini****, M. Viri, C. Zucca, G. Capovilla, A. R. Giovagnoli*, M. P. Canevini, S. Binelli*, M. Casazza*, A. T. Cantisani*****, A. Filla**, M. Pezzella**, M. Santucci, A. Parmeggiani, A. Posar, G. De Maria, C. Marini, A. Bianchi, F. Ragona***, E. Freri***, C. Mariotti*, and P. Costa****** *IRCCS Foundation Besta Neurological Institute, Milan, Italy; Bellaria Hospital, Bologna, Italy; University of Messina, Messina, Italy; Bologna, Italy; G. Gaslini Institute, University of Genova, Genova, Italy; **Federico II University of Napoli, Napoli, Italy; University Polyclinic, Catanzaro, Italy; Bari Polyclinic, Bari, Italy; IRCCS Neurolesi, Messina, Italy; Maggiore Hospital of Bologna, Bologna, Italy; ***IRCCS Foundation Neurological Institute C. Besta of Milan, Milan, Italy; IRCCS Monzino, Pavia, Italy; University of Salerno, Salerno, Italy; S. Anna Hospital, Como, Italy; I.R.C.C.S. Foundation Neurological Institute, Milan, Italy; **** University of Florence, Meyer Hospital, Florence, Italy; Fatebenefratelli hospital, Milan, Italy; IRCSS La Nostra Famiglia, Bosisio Parini, Italy; Hospital of Mantova, Mantova, Italy; S. Paolo Hospital, University of Milan, Milan, Italy; *****Perugia, Italy; University of Bologna, Bologna, Italy; Brescia, Italy; Florence, Italy; Arezzo, Italy; and ******Trieste, Italy
Purpose: Progressive myoclonus epilepsies (PMEs) result from several genetic disorders. Few information are available about the prevalence of different PMEs. In spite of the progress in bio-molecular fields, the causative disorder remains undiagnosed in a significant fraction of the patients presenting with a PME phenotype. The aim of this study was collecting information about the frequency and geographical distribution of PMEs in Italy. Method: The Genetic Commission of the Italian League against epilepsy set up a data-base to include information dealing with PME patients referred by Italian Epilepsy Centres, including the following information: geographical origin of the parents, consanguinity, familiarity, age at the disease and myoclonus onset, general characteristics of the seizures and myoclonus and associated neurological defects, positive diagnosis, when reached. Negative results obtained in the different examinations performed during the diagnostic work-up had to be explicitly reported for the patients who didn't reach a positive diagnosis of the neurological disorder underlying the PME phenotype. Result: We collected 179 patients, including 74 with Unverricht-Lundborg disease, 33 with Lafora body disease, 25 with PME forms resulting from more rare genetic causes (neuronal ceroid-lipofuscinosis, action myoclonus renal syndrome, mitochondrial encephalopathies, other metaEpilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x
p828 COMORBIDITIES IN ROLANDIC EPILEPSY Y. A. Hernandez Vega*, S. Tang, A. Smith*, T. Clarke, and D. K. Pal *Clinical Neuroscience PO43, London, UK; King's College Hospital, London, UKColumbia University, New York, NY, USA; and King's College London, London, UK
Purpose: Rolandic Epilepsy (RE) has been associated with several neurocognitive (speech sound disorder, reading disability, ADHD) and neurological (migraine) comorbidities. There is evidence that these comorbidities are not only familial but genetic in origin. Our objective is to estimate the distribution of comorbidities in RE patients and siblings. Method: We recruited RE 105 patients and their 130 siblings for a genetic study from 2004 to 2012 in the USA and UK. We systematically and prospectively collected data on demographic, seizure and treatment variables, speech sound disorder, reading disability, ADHD, migraine and school failure. We calculated Mantel-Haenszel odds ratios of association using STATA, adjusting for demographic and clinical variables. Result: 40% of probands had reading disability; 40% school failure; 30% speech sound disorder; 18% ADHD symptoms; and 13% migraine. Among siblings, 20% had reading disability; 22% school failure; 18% speech disorder; and 11% migraine. 53% of probands had at least one neurocognitive comorbidity and 32% of siblings had at least one language-related comorbidity. In multivariate analysis, reading disability is the only independently associated risk factor for school failure (Odds Ratio=104) after adjusting for speech sound disorder, ADHD, age at onset, seizure frequency, and treatment. Conclusion: Over half of RE patients and one-third of their siblings are at risk of neurocognitive comorbidities. School failure occurs in a very high proportion of patients and siblings and is predicted by reading disability. RE patients should be neuropsychologically evaluated early in the course of disease to mitigate educational complications. Families should be advised about the risk of neurocognitive impairments in siblings
p829 ELECTROENCEPHALOGRAPHIC FOCAL DISCHARGES WITH OR WITHOUT CLINICAL MANIFESTATIONS IN CHILDREN WITH CHILDHOOD ABSENCE EPILEPSY Z. Sabol, M. Kovac Sizgoric, and F. Sabol Sabol Clinic for Sick Children, Zagreb, Croatia
Purpose: The aim of this study was to establish the frequency of focal electroencephalographic (EEG) discharges with or without clinical manifestations in children with childhood absence epilepsy (CAE). Method: Patients and methods: During 13-years period (19982011) we have been treated and followed-up 81 patients (39 girls and 42 boy), at the age from 1.8 to 13.5 years (median age 6.9 years) with typical absences. Average duration of clinical follow-up was six years. Result: Results: In 13/81 (16%) children with CAE focal EEG discharges were revealed changes identical to those in benign partial epilep-
241 Abstracts
sies (BPE). Six from 11 patients manifested also partial seizures suitable for Panayiotopoulos syndrome (PS) (4), benign rolandic epilepsy (1) and benign partial epilepsy with occipital paroxysms - Gastaut type (1 patient). The age of children at the time of the first partial seizure was 1.7 - 11 years. In all patients the absence seizure control was achieved inside six weeks - 11 months. Focal EEG discharges were disappeared in 10/13 patients, in three are still present, but without relapse of partial seizures. Conclusion: Evidence of focal EEG discharges, with or without evident partial seizures in patients with CAE is rare, but possible. Although relationship between partial and generalized seizures in the same patient can be coincidental, the posibility of its genetic linkage cannot be excluded. Further clinical investigations about clinical and EEG features, the results of treatment and establishment of long-term prognosis in these patients could lead us to the definition of special form of CAE. likely to affect that risk. The aims of study was to determine patient and family attitudes towards the fear of antiepileptic drug withdrawal, after three years of seizure controle. Method: This research was carried out in the Institute for Child and Youth Health care of Vojvodina. During the study, which lasted from 2003 to 2008, a face-to-face interview about fear of antiepileptic therapy withdrawal was done, during adolescent patient examination. Study population included 150 adolescent patients, and 265 their parents. Result: Accepted risk in general is higher in our adolescent patients group than in parents group (p<0.05). This risk over 50% seem excessive to all parents, but not to all adolescent patients. Conclusion: Its important to admire adolescent patients and their parents fear towards the risk of antiepileptic drug withdrawal.
p830 EPILEPSY AND PCDH19 MUTATION CLINICAL AND ELECTROPHYSIOLOGICAL FEATURES IN 13 PATIENTS N. Chemaly*, A. Kaminska*, J. M. Pinard, A. Gauthier, C. Chiron, I. An, I. Desguerre, N. Bahi Buisson, O. Dulac, and R. Nabbout* *Hopital Necker Enfants Malades, Paris, France; Hpital Raymond Poincar, Garches, France; CHU Nantes - Hpital Mre enfant, Nantes, France; Hpital Necker Enfants Malades, Paris, France; and Hpital Piti Salptrire, Paris, France
Purpose: Mutations in PCDH19 gene were described in Epilepsy in Female with Mental Retardation and in patients presenting an epileptic encephalopathy similar to Dravet syndrome. Method: In order to precise the clinical and electrophysiological phenotype associated with PCDH 19 mutation, we included 13 patients followed in our institution with a mutation in this gene. We retrospectively reviewed clinical history, seizure and EEG characteristics, cognitive and behavioral assessment. Result: Seizures were mainly focal at onset. Fever susceptibility was not systematic at onset (4/13 patients) but was found in all patients during follow-up. Seizures occurred in clusters of focal or generalized seizures, mainly during febrile episodes. Early EEGs recordings before the age of 12 months showed diffuse rhythmic slow wave with fast activity. During seizures clusters, we recorded seizures with temporal or frontal onset and interictal focal spikes and slow waves in the same regions. During follow-up, interictal EEG showed generalized slowing of the back ground activity, theta activities in the central regions. The frequency of clusters decreases during the second decade, being less than once a year in 5 patients with one patient seizure free without AEDs. Cognitive impairment is constant after the age of 3. Autistic features were confirmed in 3 patients. Psychiatric features consist of aggressive and frontal behavior. Conclusion: This phenotype seems different from Dravet syndrome phenotype regarding semiology of seizure, onset of fever susceptibility, cognitive impairment and psychiatric symptoms. The phenotypic spectrum is homogeneous in this cohort and helps to better delineate the PCDH19 mutations phenotype.
p832 FOCAL EPILEPTIFORM DISCHARGES IN PEDIATRIC PATIENTS WITH IDIOPATHIC GENERALIZED EPILEPTIC SYNDROMES N. Ermolenko Voronezh State Medical Academy, Voronezh, Russian Federation
Purpose: The occurrence of focal and clinical EEG abnormalities in certain idiopathic generalized epilepsy (IGE) syndromes is common and may require extensive study to make a differential diagnosis. The aim of this study was to identify the prevalence of various focal electroencephalographic and/or clinical features in patients with different forms of IGE, required video-EEG monitoring. Method: We retrospectively studied 71 patients younger than 18 years of age (31 males and 42 females) with IGE who underwent video EEG monitoring between January 2004 and June 2010. Two consultants independently read all EEGs and reported their findings. Exclusion criteria: abnormal interictal EEG, mental retardation, resistance to antiepileptic drugs. 509 seizures were evaluated in 71patients. Result: All the patients had generalized epileptiform discharges. Focal EEG abnormalities were noted in 45% cases. Video-EEG monitoring captured focal features of seizures in 15.5% of patients. All patients did not respond to traditional therapy and became seizure-free after treatment with ADEs appropriate for absence or myoclonic seizures. Conclusion: This study supports the hypothesis of a more continuous transition between focal and generalized epilepsies in contrast to the present concept of a stringent pathophysiologic dichotomy. The diagnosis of IGEs is very demanding for patients with atypical features with regard to seizure type, EEG findings, and response to appropriate AEDs.
p831 FEAR TOWARDS THE ANTIEPILEPTIC THERAPY WITHDRAWAL M. F. Knezevic-Pogancev Institute for Child and Youth Health Care of Vojvodina, Novi Sad, Serbia
Purpose: The decision of antiepileptic drugs withdrawal is mostly based on a balanced view of the overall risk of seizure relapse and factors most
p833 EPILEPSY IN PATIENTS WITH CEREBRAL PALSY IS NOT ALWAYS LIFELONG CONDITION P. Ignjatovic, and N. J. Jovic Clinic of Neurology and Psychiatry for Children and Youth, Belgrade, Serbia
Purpose: The aim of the study was to analyze the clinical prognosis and outcome of epilepsy in children and young adults with cerebral palsy (CP). Method: This retrospective study included 61 subjects with CP (52 with spastic form and 9 with mixed form) and epilepsy, both genders, aged from 5 to 32 years (mean 14) followed for mean 8.5 years (range 315). Result: Thirty-nine % of studied children had their first seizure within the first 12 months of life. Infantile spasms occurred in 13% and 75% of
242 Abstracts
these patients later developed focal seizures. Fifty-six % had one seizure type, 41% had two, while 3% developed three types of seizures. Focal seizures with or without secondary generalization were the most common types. Cognitive impairment has been found in 69%. Intractable epilepsy developed in 26% of patients, predominantly in children with severe to profound mental retardation and with serious ambulatory disability. After 310 years of seizure freedom, antiepileptic drugs (AEDs) were discontinued in 13 patients. Sixty-two % of this group remained seizure-free without AED treatment for at least 1 year, but 38% had recurrences. Stable remission without AED was achieved in 5 of 6 children with spastic diplegia, 2 of 5 patients with spastic hemiparesis and in one of two subjects with mixed CP form. Conclusion: Complete seizure control was achieved in three-quarters of children with CP and epilepsy. Almost two-thirds of patients with terminal remission remained seizure-free after AED discontinuation. Patients with spastic diplegia showed the lowest recurrence rates. Purpose: To describe a kindred with deletion of the KCNQ2 gene, a highly variable phenotype and correlation with loss, rather than alteration of function. Method: We describe the genetic analysis of chromosome 20q13.33 in an infant with a severe, infantile epilepsy and affected family members without epilepsy. Result: The proband developed focal convulsive seizures associated with apnoea at three weeks of age. Ictal EEG demonstrated low amplitude fast activity bilaterally, with evolution over the right centrotemporal region. Over the next weeks the seizures occurred frequently and she subsequently had status epilepticus. Her development and neurological examination have remained normal. With topiramate and clobazam therapy her seizure frequency reduced. Aged 15 months she has been seizure free for 6 months. She received extensive investigation for an epileptic encephalopathy, all of which was normal, with the exception of array CGH. This revealed a 216kb genomic deletion using Affymetrix GeneChip 6.0 SNP array. The deletion includes the KCNQ2 gene. Further investigation in the family showed this to be familial but non penetrant in first and second degree relatives. Conclusion: The variability in severity of the infantile epilepsies associated with KCNQ2 has been reported to be due to mutation type. This kindred further demonstrates that loss of function mutations can be benign and associated with minimal clinical phenotype, or with a severe epilepsy in the neonatal/infantile period which remits over the first year.
p834 COMORBIDITY IN CHILDHOOD EPILEPSY IN CLINICAL PRACTICE A. Garcia Ron*, R. Blanco Lago*, C. Rodriguez Riero*, J. Herreros Rodriguez, L. Ballesteros Plaza*, and M. A. De La Morena Vicente *Hospital Universitario Infanta Cristina, Madrid, Spain; and Hospital Infanta Cristina, Madrid, Spain
Purpose: There are few studies about comorbidity in childhood epilepsy. Our objective was to analyze the neurological, psychiatric and systemic diseases in children with epilepsy, in outpatients of neuropediatric a level II hospital. Method: We reviewed medical records of children with epilepsy with at least a year of follow up. Patients with febrile seizures and acute symptomatic seizures were excluded We collected demographic data, comorbidity, drug responsiveness, visits to emergency department visits and unplanned consultations to pediatric neurologist for seizures. Result: We include 46 patients, 28.3% had systemic diseases (respiratory, cardiology, traumatology, endocrinology, otorhinolaryngology diseases, chronic infectious diseases). While 41.3% had neurological and/or psychiatric disorders (neurodevelopment disorders, attention deficit hyperactivity disorder, conduct disorder). Having account of children with drug resistant epilepsy: 100% had neurological and/or psychiatric disorders and 54.5% systemic comorbidities. With respect to the unexpected visits to emergency room or neurology office by seizures, at least once during the follow up: 32.6% of all the patients. In patients with neurological/psychiatric and systemic comorbidities this values are 52.6% and 61.5% respectively. Conclusion: In our study all the patients with drug resistant epilepsy associated neurological and/or psychiatric pathology. More than a quarter of the children presented other chronic medical diseases. Around sixty percent of epileptic children with systemic pathology consulted at least once by seizures in the follow up. It's need develop prospective studies about if systemic diseases had influenced in management and prognosis of epilepsy in this population

p836 EVALUATION OF HEALTH CARE UTILISATION AMONG ADULT PATIENTS WITH EPILEPSY IN THE DISTRICT OF MARBURG-BIEDENKOPF IN GERMANY A. Strzelczyk, T. Nickolay, S. Bauer, A. Haag, S. Knake, W. H. Oertel, P. S. Reif, J. P. Reese, R. Dodel, F. Rosenow, and H. M. Hamer Philipps-University Marburg, Marburg, Germany
Purpose: Epilepsy is a common neurological disorder and imposes a substantial burden on individuals and society as a whole. We performed a cross-sectional cohort study in adults with epilepsy irrespective of seizure severity, duration of illness and epilepsy syndrome. Patients seeking outpatient or inpatient treatment in all health care sectors in the district of Marburg-Biedenkopf were evaluated in 2008. Method: During a four month period 366 residents with epilepsy were enrolled in the study. Costs of inpatient and outpatient treatment were derived from billing data of participating hospitals and office-based physicians. Data on socioeconomic status, course of epilepsy and further direct and indirect costs were recorded using patient questionnaires. Result: Annual epilepsy-specific costs were estimated to be 7.738 per patient, while direct costs constituted 31.1% of the total costs and indirect costs comprised 68.9%. Direct medical costs were mainly due to hospitalization (33.2% of total direct costs) and anticonvulsants (26.7%). Costs of admissions were due to status epilepticus (24.4%), video-EEG monitoring (14.8%), newly diagnosed patients (14.4%) and seizure-related injuries (8.8%). Indirect costs were mainly due to early retirement (38.0%), unemployment (35.9%) and off-days due to seizures (26.2%). Conclusion: The results highlight the social impact of epilepsy that is mainly due to indirect costs. Hospitalization and medication contributed the most to the direct costs. Mean costs of epilepsy in this German population-based study were lower than in studies conducted at European epilepsy centers due to inclusion of all health care sectors.
p835 A GENOMIC DELETION ENCOMPASSING KCNQ2 CAUSES INFANTILE EPILEPSY: A FURTHER EXAMPLE OF GENOTYPE AND PHENOTYPE CORRELATION A. P. Parker*, I. Simonic*, and F. L. Raymond *Addenbrooke's Hospital, Cambridge, UK; and University of Cambridge, Cambridge, UK
243 Abstracts
p837 THE KNOWLEDGE ABOUT EPILEPSY HAS SIGNIFICANT IMPACT ON QUALITY OF LIFE IN PEOPLE WITH EPILEPSY S. Lee, and Y. Kim, D; Study Group of Knowledge About Epilepsy Asan Medical Center, Seoul, Korea
Purpose: Although PWE's knowledge about epilepsy has been thought to have an influence on their self-efficacy and quality of life (QoL), there has been no evidence in the literature. Method: Data were collected from 572 adult PWE (47.9% male, mean age: 35.8 years, range: 1869 years) in 31 secondary or tertiary hostpitals in Korea. Clinical information was obtained by neurologists and the other information was collected using self-completed questionnaires including Epilepsy Knowledge Profile-General (EKP-G) and Personal (EKP-P), Epilepsy Disclosure Scale, Hospital Anxiety Depression Scale, Stigma Scale, Drug Compliance Scale, Impact of Epilepsy Scale, Epilepsy Selfefficacy Scale and Quality of Life in Epilepsy-10 (QOLIE-10). Result: Higher level of general knowledge (EKP-G, mean: 21.9 range: 333) was significantly correlated with higher drug compliance (p=0.015) and higher self-efficacy (p<0.001). But it was not linked to QoL. In contrast, higher level of personal knowledge (EKP-P, mean: 2.8, range: 08) was significantly related to higher self-efficacy (p<0.001), lower level of depression (p=0.001), and higher mental health of QOLIE10 (p=0.000). Multivariate analysis showed two predictors for better mental health of QOLIE-10: higher level of personal knowledge and lower level of depression. Higher level of self-efficacy did not reach statistical significance (p=0.061). In statistical analyses, age, sex, education, economic status, employment status, seizure frequency, epilepsy type, and number of antiepileptic drug were adjusted. Conclusion: The level of knowledge about epilepsy had significant influences on self-efficacy, drug compliance, depression, and mental health of HRQOL. Especially, personal knowledge about epilepsy was significant and independent predictor for mental health of HRQOL in PWE. 82.7% (n=105) were unaware of the registry. Of those who'd been eligible to join, only 7 (12%) of respondents had previously done so. Conclusion: Key publications have resulted from epilepsy pregnancy registries that guide prescribing trends and pre-conceptual counselling. There is scope to increase uptake of WWE onto the UK registry, by increasing awareness amongst HCPs and WWE. This is particularly important given the introduction of new anti-epileptic drugs were pregnancy outcome data are currently limited.
p839 HEALTH RELATED QUALITY OF LIFE AND SOCIAL STIGMA IN PATIENTS WITH EPILEPSY M. Prieschl, I. Unterberger, G. Walser, M. Bergmann, G. Kuchukhidze, C. Gneiss, and G. Luef Medical University Innsbruck, Innsbruck, Austria
Purpose: Epilepsy has many non-medical effects on people with epilepsy, their family and the community. The aim of our study is to identify individual limitations, social stigma and impact on quality of life, professional life and in social interaction due to epilepsy. Method: A standardized questionnaire (PESOS) was applied to evaluate socio-demographic aspects, epilepsy specific data and individual problems of patients with epilepsy. Patients were included with a diagnosis of epilepsy (based on the International classification of epileptic seizures, epilepsies and epileptic syndromes of the League against Epilepsy), aged 18 years, seen at the University Hospital Innsbruck within one year. Result: Two hundred patients between 18 and 77 years (mean 42 y; +/) 15 y) were included out of an equivalent gender distribution (51% female, 49% male). Epilepsy diagnoses are composed of generalized seizures in 21% and focal seizures in 79%. Fortunately 68% valued their quality of life between 7 and 10 (scale: 010) and 57% were seizure free in the last six month. A negative significant correlation (a=0.01) between seizure frequency and overall quality of life as well as in the impairment due to epilepsy was observed. Discrimination due to epilepsy was reported in 30% of all patients, especially in the field of professional life (57%) and concerning driving (21%). Conclusion: Optimal seizure control is essential for long term care of patients with epilepsy. However, impaired quality of life and stigma is a major issue in patients with epilepsy. This study confirms the need for routine screening, counseling and psychosocial support for patients with epilepsy.
p838 THE UPTAKE AND KNOWLEDGE OF THE UK EPILEPSY AND PREGNANCY REGISTRY AMONGST HEALTHCARE PROFESSIONALS AND PATIENTS J. R. Howells*, J. Craig, B. Irwin, J. Morrow, and K. Hamandi *Cardiff University, Cardiff, UK; Belfast Health and Social Care Trust, Belfast, UK; and University Hospital of Wales, Cardiff, UK
Purpose: Congenital malformation rates associated with antiepileptic drugs (AEDs) are provided by epilepsy and pregnancy registries. We aimed to evaluate the uptake and knowledge of the UK epilepsy and pregnancy registry and assess recent publications from the registry to determine their affect on the prenatal management of women with epilepsy (WWE). Method: Mixed method study. Uptake was defined as the number of WWE that enrolled onto the registry divided by the estimated UK births to WWE. Questionnaires were distributed to 1,300 health care professionals (HCP) via email membership mailing lists and 650 WWE under the care of the epilepsy unit at University Hospital of Wales by post. Result: We estimated 30,33340,480 UK births were to WWE between 1996 and 2009; 7,528 women joined the epilepsy pregnancy registry within this time period, giving an uptake 18.624.8%. In our questionnaire 72 (5.5%) HCPs replied; including consultant neurologists, epilepsy nurse specialists, GPs and local midwives. 61(84.7%) were aware of the UK registry and 44 (61.1%) had previously referred or advised WWE to join. 127 (19.5%) questionnaires were returned from WWE,
p840 HEATH-RELATED QUALITY OF LIFE (HRQOL) IN RUSSIAN ADULT PATIENTS WITH EPILEPSY A. Guekht, E. Melikian, L. Milchakova, A. Lebedeva, and I. Bondareva Russian National Reaearch Medical University, Moscow, Russian Federation
Purpose: The aim of this study was to evaluate the changes in HRQOL in the Russian population of patients depending on seizure frequency reduction (SF) on treatment. Method: The HRQOL was evaluated by QOLIE-31 (Cramer, 1998) questionnaire, completed by 139 patients with epilepsy, mostly recently diagnosed, with different focal or generalized epilepsy syndromes (age (M/SD) 33.27/14.22 years; range 1874) at the initiation of treatment and in six months. Result: Overall QOLIE-31 scores in the Russian population, both at baseline and in follow-up, were lower, then reported from a number of European countries (Picot et al., 2004; Haritomeni et al., 2006; Tlusta et al., 2008). Compared to baseline, statistically significant changes in the overall scores were observed in the seizure-free patients (n=60) (M/SD)
244 Abstracts
(from 42.19/4.19 to 52.72/3.94), and in patients with more than 50% SF reduction (from 42.67/5.04 to 48.07/4.77)(n=31). Changes in patients with less than 50% SF reduction (n=22) and patients with no improvement (n=26) were not statistically significant. In a multivariate analysis, SF was the significant predictor of the total score and major QOLIE-31 domains: seizure worry; overall QOL, energy/fatigue, cognitive functioning, medication effects, social functioning. Conclusion: Seizure frequency in the Russian population is an important determinant of the total score and major QOLIE-31 domains. However, the overall QOLIE-31 scores are lower, than reported from a number of European countries, even in seizure free patients. Conclusion: The occurrence of epileptiform discharges and paroxysmal activity is more frequent in children presenting more severe condition, regardless of epileptic seizures. Further investigation of brain electroactivity in patients with autism spectrum disorders is inevitable and possible prophylactic treatment in patient not manifesting epileptic seizures should be concerned.
p841 KNOWLEDGE AND ATTITUDE OF NIGERIAN ADULTS IN AN URBAN CENTER B. Ezeala-Adikaibe, and A. U. Justin University of Nigeria Teaching Hospital, Nigeria
Purpose: To determine the knowledge and attitude of Nigerian adults in an urban center. Method: This study was cross-sectional and descriptive in design. Result: A total of 244 subjects who were 30 years and above were interviewed. All had previous knowledge of epilepsy, 16.4% had relatives with epilepsy, 67.2% knew someone with epilepsy and 84.8% had seen convulsion in the past. About 61.1% and 34.8% agreed that loss of consciousness and jerking of the body were some of the manifestations of seizures. Those who considered epilepsy to be due to witchcraft/demons/ charms were 31.6% and 18.9% as a psychiatric disorder. Only 33.6% accepted orthodox medicine as the only treatment and 10.7% herbalists and 17.6% prayers. During seizures 39.3% would put objects into the mouth and 10.7% would run away. Though 61.5% would make friends with someone with epilepsy, however 73.3% would not marry them. Conclusion: There is still low level of knowledge and negative attitude of epilepsy among urban dwellers in south East Nigerian. Concerted efforts should be made to improve the knowledge and attitude of the populace and improve the social and economic issues affecting people living with epilepsy.
p843 ICTAL UNILATERAL HYPERKINETIC PROXIMAL LOWER LIMB MOVEMENTS AN INDEPENDENT LATERALISING SIGN SUGGESTING IPSILATERAL SEIZURE ONSET R. Teotonio*, B. Diehl, A. W. Mcevoy, J. Duncan, and T. Wehner *UCL Institute of Neurology, London, UK; National Hospital for Neurology and Neurosurgery, London, UK; and The National Hospital for Neurology and Neurosurgery, London, UK
Purpose: Our aim was to determine the lateralizing value of ictal unilateral hyperkinetic proximal lower limb movements. Method: We reviewed all patients who underwent intracranial EEG between 2008 and 2011 at our centre and whose seizures included hyperkinetic features. We analyzed seizures for the presence of unilateral hyperkinetic proximal lower limb movements that lasted at least three seconds and their correlation with electroencephalographic ictal onset and association with other possible lateralizing signs. Result: Among 16 patients with ictal hyperkinetic features, three had unilateral proximal lower limb movements (combination of flexion/ extension and ab/adduction in the hip, usually with tonic extension in the knee), sometimes associated with hemiballic-like movements of the ipsilateral upper limb. There were no other consistent lateralising signs. In all three patients, these movements were ipsilateral to the ictal onset zone and always started few seconds after electroencephalographic seizure onset (2 to 10 seconds). In two patients, intracranial EEG showed a parietal lobe seizure onset. One of them did not proceed to surgery due to close proximity of the ictal onset zone to eloquent cortex. The other patient became seizure free following resection of the left inferior parietal lobule (pathology cortical dysplasia type 2B). In the third patient, a mesial temporal ictal onset was recorded. The patient ultimately became seizure free for the past six month after anterior temporal lobe resection (pathology hippocampal sclerosis). Conclusion: Our results suggest that ictal hyperkinetic proximal lower limb movements may be an independent lateralizing sign to the ipsilateral hemisphere.
p842 RISK FACTORS OF EPILEPSY AND CLINICAL-ELECTROENCEPHALOGRAPHICAL CORRELATION IN CHILDREN WITH PERVASIVE DEVELOPMENTAL DISORDERS K. A. Polatynska*, L. Kepczynski, and J. Wendorff* *Polish Mothers Memorial Research Institute, Lodz, Poland; and Medical University of Lodz, Lodz, Poland
Purpose: The aim was to evaluate the correlation between neurological signs and symptoms in children with pervasive developmental disorders and occurrence of paroxysmal activity and epileptiform discharges in different areas assessed in EEG examination as well as epilepsy risk factor assessment. Method: 86 patients with pervasive developmental disorders were included. The correlation between clinical symptoms and electrophysiological findings were assessed using Cohrane-Armitage v2 test. Risk factors of epilepsy was assessed by calculating OR. The p-value < 0.05 was treated as significant. Result: We have identified significant positive correlation between occurrence of paroxysmal activity and epileptiform discharges in frontocentro-temporal area and decreasing eye contact, decreasing level of functioning and number of words. Delayed motor development and intellectual disability in higher level than mild, abnormal muscle tone and delivery by caesarian section were significant risk factors.
p844 ICTAL AND POSTICTAL SPEECH IMPAIRMENT IN TEMPOROBASAL EPILEPSY: AN UNDERRECOGNIZED CLINICAL MANIFESTATION R. Toledano Delgado, I. G. Morales, A. J. Huete, and A. G. Rein Hospital Ruber Internacional, Madrid, Spain
Purpose: Besides the classic language areas, the basal temporal language area (BTLA) and the temporal pole may contribute to the functioning of the language system. However, it is not known whether these brain areas may have clinical relevance in language impairment during temporal lobe seizures. To clarify this issue we evaluated the speech manifestations of seizures caused by lesions located at the basal aspect of the temporal lobe. Method: We reviewed medical history, video-EEG recording and neuroimaging of patients who had temporal seizures caused by small lesions circumscribed to the temporobasal region over the last 12 years. Result: Of a total of 168 patients who had temporal lobe seizures registered in our epilepsy unit, 14 patients (8.3%) had small well-defined
245 Abstracts
lesions on MRI located at the BTLA or the basal aspect of the temporal pole (4 right, 10 left). Alteration of speech was only found in patients with left lesions and consisted mostly of speech arrest as well as alteration of receptive language. Despite significant language impairment, memory function seemed preserved in nine patients who showed adequate ictal behavior and could recall postictally the inability to speak and understand. Conclusion: In addition to the classic language areas, both the BTLA and the more anterior basal pole cortex may play an important role in language manifestations during temporal lobe seizures. Recognition of this type of seizures should prompt the physician to carefully reassess the basal surface of the temporal lobe looking for small lesions that otherwise could be missed. Purpose: Mutations in SCN1A may cause various epilepsy syndromes including generalized epilepsy with febrile seizures plus (GEFS+), a usually mild generalized epilepsy and Dravet Syndrome, a severe epileptic encephalopathy of infancy. Both entities are usually distinct and Dravet syndrome is rarely seen in GEFS+ families. We describe the clinical and molecular findings in a large GEFS+ family with a heterogeneous, but unusually severe familial phenotype. Method: A large GEFS+ pedigree with 13 affected individuals was phenotyped and genetic analysis for SCN1A was performed. Result: In the presented GEFS+ family, two infants from different branches had classic Dravet syndrome and borderline Dravet Syndrome (SMEB), respectively. Various Febrile Seizure Plus (FS+) phenotypes were present in all other affected family members. A novel A G missense mutation in exon 21 in SCN1A resulting in a lysine to glutamine change was found in the proband with Dravet Syndrome, and her father who had childhood febrile seizures but is otherwise unaffected, in her 8-month-old as yet asymptomatic brother and in the SMEB case. Conclusion: The findings in this family confirm previous observations of marked intrafamilial clinical variability in GEFS+, but the overall familial epilepsy spectrum is more severe than usually observed. We hypothesize that certain SCN1A mutations may result in more severe familial GEFS+ phenotypes in conjunction with modifier genes to explain the observed phenotypic heterogeneity. In these families, the risk of severe epilepsy including Dravet Syndrome may be significantly higher than usually seen in GEFS+, resulting in profound implications for genetic counseling.
p845 SEIZURE RESPONSE DOGS FOR CHILDREN'S NOCTURNAL SEIZURES: UPDATE ON CONSUMER INVOLVEMENT AND FEASIBILITY STUDY K. Jeavons*, S. Ganesan, M. Prasad, N. Hussain, S. Mordekar, C. Picton, A. Brown, W. P. Whitehouse, and R. Howson *Nottingham University Hospitals, Nottingham, UK; Leicester; Sheffield; Nottingham; and Support Dogs, Sheffield, UK
Purpose: The National Institute for Clinical Excellence advocates the use of benzodiazepines for prolonged convulsive seizures. Anecdotal reports suggest that family pet dogs may alert carers to the presence of seizures. Seizure Response dogs are dogs which have been specifically trained to alert families to the presence of a seizure in children and the aim of this consumer involvement exercise was to assess the feasibility of pursuing a clinical trial into the efficacy and reliability of Seizure Response dogs. Preliminary results were presented at the International League Against Epilepsy- UK chapter meeting in 2011. Method: A convenience sample of parents of children with nocturnal seizures were asked to complete a brief questionnaire about their child's seizures, emergency medication, and whether they had a dog or would consider having one in the future. Data was entered into Excel and simple descriptive statistics used. Result: Completed questionnaires were received by 68 families of children who had had at least one nocturnal seizure within the preceding year. 36/68 (53%) had a rescue medication, such as buccal midazolam, for prolonged seizures. 22/68 (32%) had a frequency of nocturnal seizures of at least one a week and 13/68 (19%) had at least one seizure every night. The mean age was 10 years and 1 month, however 41/68 (60%) of carers reported sleeping in the child's room or bed within the preceeding month. 48/68 (71%) of families would be interested in being involved with future research in this area. Conclusion: Families responded positively to the concept of Seizure Response dogs.
p847 ELECTRIC SOURCE IMAGING (ESI) IN PRESURGICAL EPILEPSY INVESTIGATIONS: DENSE ELECTRODE CONFIGURATIONS AND SUFFICIENT COVERAGE OF THE TEMPORAL LOBES IS NECESSARY FOR CORRECT RESULTS G. Lantz, M. Terrill, T. Gilbert, P. Luu, A. Bunnenberg, D. Tucker Electrical Geodesic Inc, Eugene, Oregon, USA
Purpose: In Electric Source Imaging (ESI) correct source localizations require both a sufficient number of recording electrodes and adequate spatial coverage of the head surface. New EEG systems now allow recording with up to 256 surface electrodes. In this study we compared the localization accuracy of epileptic spikes recorded with 256 electrodes to that with sparser, incomplete or uneven electrode coverage. Method: In four patients with intracranially verified temporal lobe epilepsy, the ictal onset location in 3D was determined in the intracranial electrodes. Interictal spikes recorded with 256 electrodes were averaged. To determine the importance of spatial sampling density a regular downsampling of the averaged spike was performed to 128, 64 and 32 electrodes. The importance of sufficient coverage of all areas was assessed by taking out electrodes in the lower temporal areas. With a distributed source model (LAURA) the source maximum was localized with both the original 256 channel and the downsampled spikes, and the localizations were compared to the intracranial ictal onset. Results: Both regular downsampling and reduced temporal lobe coverage resulted in a clear deterioration of the ESI results. The most correct source localizations with respect to the intracranial ictal onset were obtained with the 256 channel setup. Conclusion: In order to obtain optimal results with ESI both a dense sampling on the head and a sufficient coverage of the lower temporal areas is necessary. Improvement of the results can be obtained at least up to 256 electrodes. Acknowledgement: This project was supported by Electrocal Geodesic Inc.
p846 AN UNUSUALLY SEVERE PHENOTYPE IN A FAMILY WITH A NOVEL SCN1A MUTATION: FROM GEFS+ TO DRAVET SYNDROME H. Goldberg-Stern*, Z. Afawi, S. Aharoni*, O. Bennett, S. Appenzeller, A. Baumgart, L. Basel-Vanagaite, G. Kuhlenbaumer, A. D. Korczyn, and I. Helbig *Schneider Children's Medical Center of Israel, Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Hadassah-Hebrew University Medical Center, Jerusalem, Israel; Univeristy Medical Center SchleswigHolstein, Kiel, Germany; and Raphael Recanati Genetics Institute, Petach Tikva, Israel

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Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.

10th European Congress on Epileptology London, UK, 30 September4 October 2012

Genetics 1 Monday, 01 October 2012

Basic Science 1 Monday, 01 October 2012

Clinical Epileptology Monday, 01 October 2012

Neuropsychiatry Monday, 01 October 2012

Antiepileptic Drugs Monday, 01 October 2012

Clinical Pharmacology and Therapeutics Tuesday, 02 October 2012

Genetics 2 Tuesday, 02 October 2012

Neuropsychology Tuesday, 02 October 2012

Surgical Treatment Tuesday, 02 October 2012

Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

Clinical Neurophysiology Tuesday, 02 October 2012

Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

Functional MRI Wednesday, 03 October 2012

Structural and Functional Imaging Wednesday, 03 October 2012

Paediatric Epilepsy Wednesday, 03 October 2012

Symptomatic Epilepsy Wednesday, 03 October 2012

Basic Science 2 Wednesday, 03 October 2012

Basic Science 1 Monday, 01 October 2012

Mario Negri Institute for Pharmacological Research, Milano, Italy

Basic Science 2 Monday, 01 October 2012

Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

Basic Science 3 Monday, 01 October 2012

Basic Science 4 Monday, 01 October 2012

Epilepsy Surgery 1 Monday, 01 October 2012

Epilepsy Surgery 2 Monday, 01 October 2012

Genetics 1 Monday, 01 October 2012

Genetics 2 Monday, 01 October 2012

Genetics 3 Monday, 01 October 2012

Medical Therapy and Pharmacology 1 Monday, 01 October 2012

Medical Therapy and Pharmacology 2 Monday, 01 October 2012

Medical Therapy and Pharmacology 3 Monday, 01 October 2012

Neuroimaging and Neurophysiology 1 Monday, 01 October 2012

Neuroimaging and Neurophysiology 2 Monday, 01 October 2012

Neuroimaging and Neurophysiology 3 Monday, 01 October 2012

Paediatric Epileptology 1 Monday, 01 October 2012

Semiology, Aetiology and Classification 1 Monday, 01 October 2012

Semiology, Aetiology and Classification 2 Monday, 01 October 2012

Semiology, Aetiology and Classification 3 Monday, 01 October 2012

Semiology, Aetiology and Classification 4 Monday, 01 October 2012

Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

Semiology, Aetiology and Classification 5 Monday, 01 October 2012

Semiology, Aetiology and Classification 6 Monday, 01 October 2012

Semiology, Aetiology and classification 7 Monday, 01 October 2012

Semiology, Aetiology and Classification 9 Monday, 01 October 2012

Semiology, Aetiology and Classification 10 Monday, 01 October 2012

Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

Semiology, Aetiology and Classification 10 Monday, 01 October 2012

Basic Science 5 Tuesday, 02 October 2012

Basic Science 5 Tuesday, 02 October 2012

Basic Science 6 Tuesday, 02 October 2012

Basic Science 7 Tuesday, 02 October 2012

Basic Science 8 Tuesday, 02 October 2012

Epilepsy Surgery 3 Tuesday, 02 October 2012

Epilepsy Surgery 4 Tuesday, 02 October 2012

Medical Therapy and Pharmacology 4 Tuesday, 02 October 2012

Medical Therapy and Pharmacology 5 Tuesday, 02 October 2012

Medical Therapy and Pharmacology 6 Tuesday, 02 October 2012

Medical Therapy and Pharmacology 7 Tuesday, 02 October 2012

Neuroimaging and Neurophysiology 4 Tuesday, 02 October 2012

Epilepsia, 53(Suppl. 5):1245, 2012 doi: 10.1111/j.1528-1167.2012.03677.x

Neuroimaging and Neurophysiology 5 Tuesday, 02 October 2012