Neurological Disorders

https://www.ucsfhealth.org/conditions/neurological_disorders/
Neurological disorders are diseases of the brain, spine and the nerves that connect them. There are more than 600
diseases of the nervous system, such as brain tumors, epilepsy, Parkinson's disease and stroke as well as less
familiar ones such as frontotemporal dementia.
UCSF Medical Center is one of the top hospitals in the nation in neurology and neurosurgery, according to U.S. News
& World Report. We treat conditions from the common to rare and draw on our research to provide the most
advanced therapies available.
We have one of the largest brain tumor treatment programs in the United States and one of California's largest
cerebrovascular surgery programs. Our advanced treatments include Gamma Knife radiosurgery, which delivers a
finely focused, high dose of radiation precisely to its target. It is used to treat small to medium size tumors, epilepsy,
trigeminal neuralgia and abnormal blood vessel formations deep in the brain.
In Northern California, we have the only comprehensive memory disorders center and the largest center for the
treatment ofParkinson's disease. We also have leading experts in the treatment of peripheral nerve disorders such
as Lou Gehrig's disease or amyotrophic lateral sclerosis (ALS), a progressive degeneration of nerve cells controlling
muscle movements.
Neurological support groups for patients and their families are open to the public.

https://www.ucsfhealth.org/treatments/gamma_knife/index.html

Gamma Knife

The Gamma Knife is an advanced radiation treatment for adults and children with small to medium brain tumors,
abnormal blood vessel formations called arteriovenous malformations, epilepsy, trigeminal neuralgia, a nerve
condition that causes chronic pain, and other neurological conditions.
Despite its name, the Gamma Knife isn't a knife but is a machine that delivers a single, finely focused, high dose of
radiation to its target, while causing little or no damage to surrounding tissue. Abnormalities measuring less than 3
centimeters, or 1 inch in diameter, can be treated with the Gamma Knife.
Today, patients with serious disorders can be treated with this noninvasive procedure in one day with no overnight
hospital stay.
UCSF Medical Center, which launched its Gamma Knife Radiosurgery Program in 1991, was the first medical
center in Northern California to use a Leksell Gamma Knife to treat brain disorders. Since then, more than 3,600

patients have been treated using this state-of-the-art equipment. In 2007, UCSF acquired thePerfexion Leksell
Gamma Knife, which offers the most precise treatment with improved patient comfort.
In 2011, UCSF acquired an Extend Frame for the Gamma Knife that enables multi-session treatments, called
fractionated treatments, for larger lesions or those in more sensitive locations.

Who Should Have Gamma Knife Treatment

Factors considered in evaluating a patient for Gamma Knife treatment include a patient's age and general medical
condition, location and size of the brain abnormality and previous treatments. If it is decided that Gamma Knife is not
the best treatment option, other treatments will be discussed.
Some conditions are more effectively treated with a non-invasive radiosurgery device called the CyberKnife that uses
a robotic arm to deliver highly focused beams of radiation. At UCSF, the CyberKnife is used to treat areas of the body
that can't be treated by other radiosurgery techniques, such as the spine or spinal cord.
Radiation exposure to other parts of the body is extremely low, making it an excellent option for children and women
of childbearing age.
If you're treated at UCSF, your referring doctor plays an important role. He or she will be consulted during all phases
of your treatment.
Patients who are candidates for Gamma Knife are reviewed at our weekly Gamma Knife conference. Each patient's
condition is evaluated by a team including neurosurgeons, radiation oncologists, physicists, neuro-radiologists, neurooncologists, nurses and radiation therapists.

Preparing for Treatment

Prior to a Gamma Knife procedure, patients visit the hospital for possible blood tests, and to meet with the doctors
and nurse who will participate in the procedure. Depending on your condition, your doctors may include a radiation
oncologist or neurosurgeon. During your pre-procedure consultation, your doctor will record your medical history,
perform a physical examination and provide time for you to ask questions. Read more about preparing for the
procedure.

Procedure
The technique that allows the Gamma Knife to precisely target areas within the brain is called stereotaxy. Stereotactic
radiosurgery is performed with the aid of imaging techniques called computerized tomography (CT)
scanning, magnetic resonance imaging (MRI) and angiography. These are used together with special computerassisted instruments to provide 3-D views of the target and surrounding brain structures. By studying these images,
your doctor can accurately locate the abnormality within the brain, then precisely focus the gamma radiation beams
on the abnormality.
The neurosurgeon will use local anesthesia to numb four spots on your scalp and forehead before attaching a
"stereotactic frame." This frame allows highly precise treatment.
The treatment time will depend on your diagnosis. While the treatment is administered, you will lie on a treatment
couch. Your head will be held still during the session while 192 small radiation beams are focused simultaneously at
the target. The size of the focal spot can be adjusted and multiple focal spots can be combined together to deliver a
high radiation dose precisely to one target or to multiple targets of almost any shape, anywhere in the brain.
During treatment, there's no pain. After treatment, the head frame is removed and small adhesive bandages are
applied where the sterotactic frame was secured.

Recovery
You may be discharged shortly after the procedure. Some patients experience a mild headache, which can be treated
with medication. Discharge and follow-up instructions will be explained and you'll receive an instructional handout.

Our nurse will call you the following day to check on your status and answer any questions you may have.
The process of Gamma Knife treatment for children is similar to the process for adults, but special care is provided for
pediatric patients including imaging studies before treatment, anesthesia tailored for children, recovery and
subsequent treatment, if required.

http://www.uptodate.com/contents/whats-new-in-neurology
What's new in neurology
Authors
John F Dashe, MD, PhD
Janet L Wilterdink, MD
April F Eichler, MD, MPH
Contributor disclosures
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jul 2016. | This topic last updated: Aug 11, 2016.
The following represent additions to UpToDate from the past six months that were considered by the
editors and authors to be of particular interest. The most recent What's New entries are at the top of each
subsection.
CEREBROVASCULAR DISEASE
Risk of stroke after transient ischemic attack or minor stroke (May 2016)
In a report from the TIAregistry.org project, a prospective multinational registry of over 4700 patients with
transient ischemic attack (TIA) or minor stroke who were seen at sites providing urgent evaluation by
stroke specialists, the estimated risks of stroke at days 2, 30, 90, and 365 after the index event were 1.5,
2.8, 3.7, and 5.1 percent, respectively [1]. These rates are lower than those previously reported
(estimated as 10 to 17 percent over the first 90 days), possibly due to the more rapid implementation of
newer and more effective strategies for the secondary prevention of ischemic stroke. (See "Initial
evaluation and management of transient ischemic attack and minor ischemic stroke", section on 'Risk of
recurrent stroke'.)
Stenting versus surgery for carotid artery stenosis (March 2016)
Two recent studies have compared carotid artery stenting (CAS) and carotid endarterectomy (CEA) for
treatment of carotid artery stenosis. Accumulating evidence suggests that both CAS and CEA provide
similar long-term outcomes for patients with asymptomatic and symptomatic carotid occlusive disease,
although the periprocedural risk of stroke and death is higher with CAS.

In a meta-analysis of older adult patients with symptomatic carotid disease, pooled patient-level
data from four trials found that the periprocedural risk of stroke and death increased with age
(hazard ratio [HR] 2.2 for ages 65 to 69 and 4.2 for age 80 years) for patients assigned to CAS,
while there was no increase in periprocedural risk by age for CEA [2]. The periprocedural risk of
stroke and death was significantly increased with CAS compared with CEA for patients age 70 and
older. (See "Management of symptomatic carotid atherosclerotic disease", section on 'Effect of
age'.)
The ACT I randomized trial in patients with asymptomatic 70 to 99 percent carotid stenosis
assigned 1453 patients to either CAS or CEA [3]. For the primary composite endpoint (death, stroke,
or myocardial infarction within 30 days of the procedure or ipsilateral stroke within one year), the
prespecified statistical margin for noninferiority of stenting compared with endarterectomy was met.
The cumulative five-year rates of stroke-free survival at CAS and CEA were 93.1 and 94.7 percent,
respectively. (See "Management of asymptomatic carotid atherosclerotic disease", section on
'Stenting trials'.)
Because of higher rates of short-term complications with CAS, we continue to prefer CEA for most
medically stable patients who have symptomatic carotid stenosis or who have a life expectancy of at least
five years and high grade (80 percent) asymptomatic carotid stenosis at baseline or progression to 80
percent stenosis despite intensive medical therapy.
DEMENTIA
Proton pump inhibitors and risk of dementia in older adults (February 2016)
A new study has identified a possible link between proton pump inhibitors (PPIs) and risk of dementia in
older adults. In a prospective cohort study of >73,000 adults aged 75 years and older who were free of
dementia at baseline, regular use of a PPI was associated with a 1.4-fold increase in the risk of incident
dementia, independent of age, gender, depression, stroke, heart disease, and polypharmacy [4]. Possible
factors that could contribute to this finding include PPI-induced vitamin B12 deficiency or an interaction
between PPIs and amyloid beta deposition, although these factors were not examined in this study. On
the other hand, the association may reflect residual confounding by factors related to both use of PPIs
and the development of dementia, and more studies are needed to confirm or refute this
association. (See "Epidemiology, pathology, and pathogenesis of Alzheimer disease", section on
'Medications'.)
Declining incidence of dementia (February 2016)
A growing number of studies indicate that the incidence of dementia may be declining in high-income
countries, concomitant with a decline in the prevalence of many vascular risk factors. As an example,
using data from over 5000 patients enrolled in the Framingham Heart Study in the United States, the fiveyear cumulative hazard rate for dementia fell from 3.6 per 100 persons during the late 1970s to 2.0 per
100 persons in the late 2000s [5]. The risk reduction was only found among individuals with at least a high
school diploma, and the magnitude of the change was higher for vascular dementia than for Alzheimer
disease. Rates of hypertension, stroke, and atrial fibrillation also fell over the same time period, while
rates of obesity and type 2 diabetes rose, and it is not certain what factors account for the decreased

incidence of dementia. Despite these trends, the global total burden of dementia is expected to continue
rising as the population ages. (See "Treatment and prevention of vascular dementia", section on 'Risk
factor management'.)
DEMYELINATING DISEASE
Daclizumab approved in the US for treating relapsing-remitting multiple sclerosis (June 2016)
Daclizumab, a humanized monoclonal antibody, was recently approved by the US Food and Drug
Administration for the treatment of relapsing-remitting multiple sclerosis [6]. The approval was based upon
evidence from two randomized controlled trials that daclizumab is effective for reducing relapse rates, and
evidence from one trial that it may be effective for reducing disability progression. However, the clinical
utility of daclizumab is likely to be limited by the risk of serious adverse events, including hepatotoxicity
and infection, making it a second- or third-line agent for patients who have had an inadequate response to
two or more disease-modifying agents for relapsing-remitting multiple sclerosis. Daclizumab will be
available in the United States only through a restricted distribution program. (See "Disease-modifying
treatment of relapsing-remitting multiple sclerosis in adults", section on 'Daclizumab'.)
EPILEPSY
Long QT syndrome mutations and sudden unexpected death in epilepsy (May 2016)
Sudden unexpected death in epilepsy (SUDEP) accounts for up to one-third of premature deaths in
patients with epilepsy, and the pathophysiologic mechanisms are not well defined. A new study suggests
that some patients may be predisposed to SUDEP due to congenital long QT syndrome (LQTS). In
a study of 61 SUDEP cases for which whole blood was available at autopsy, exome sequencing
identified pathogenic LQTS mutations in four patients [7]. An additional nine patients had candidate
pathogenic variants in dominant cardiac arrhythmia genes. Prospective studies are needed to determine
whether electrocardiogram monitoring or other strategies can identify patients at risk for SUDEP and lead
to interventions to reduce risk in patients with epilepsy. (See "Sudden unexpected death in epilepsy",
section on 'Genetic factors'.)
Brivaracetam approved for focal-onset seizures in adults (March 2016)
Brivaracetam, a new antiseizure drug with a mechanism of action similar to levetiracetam, has recently
received regulatory approval in the United States and Europe for treatment of focal-onset seizures in
adults. In the largest individual trial of 768 adults with refractory focal epilepsy, brivaracetam at doses of
both 100 and 200 mg/dayreduced seizure frequency by 50 percent in approximately 38 percent of
patients, compared with 22 percent of patients assigned to placebo [8]. The most common side effects
are somnolence, dizziness, fatigue, and nausea; rare cases of bronchospasm and angioedema have
been reported [9]. Across multiple trials, psychiatric side effects have occurred more commonly in patients
treated with brivaracetam than placebo (13 versus 8 percent). Brivaracetam does not induce drugmetabolizing enzymes in the liver and will be available in both oral and intravenous
formulations. (See "Antiseizure drugs: Mechanism of action, pharmacology, and adverse effects", section
on 'Brivaracetam'.)

Levetiracetam as adjunct to benzodiazepine does not provide benefit for out-of-hospital adult
status epilepticus (February 2016)
Out-of-hospital administration of a benzodiazepine by paramedics for initial treatment of status
epilepticus can hasten seizure control, although up to 40 percent of patients will still be seizing upon
arrival to the hospital. There appears to be no benefit to the addition of levetiracetam in this setting,
however. In a randomized trial, 107 adults with status epilepticus received prehospital treatment with
intravenous clonazepam plus either levetiracetam or placebo [10]. Rates of seizure control at 15 minutes
were not improved by combined treatment compared with clonazepam alone (74 versus 84 percent), nor
were any secondary endpoints, including recurrent seizure activity, need for intubation, and length of
hospital stay. (See "Convulsive status epilepticus in adults: Treatment and prognosis", section on 'Out-ofhospital/prehospital treatment'.)
NEUROMUSCULAR DISEASE
Zika virus and Guillain-Barre syndrome (March 2016)
Zika virus has been associated with Guillain-Barre syndrome (GBS), although a direct causal relationship
has not been definitively established. A case-control study in French Polynesia evaluated the association
between GBS and Zika virus infection during the 2013 to 2014 outbreak [11]. Cases included 42 patients
diagnosed with GBS; one control group included 98 patients with nonfebrile illnesses and a second
control group included 70 patients with Zika virus infection in the absence of neurological complications.
Zika IgM was positive in 93 percent of GBS cases (versus 17 percent of patients in the first control group);
serologic evidence of past dengue infection was similar among all three groups. Antiglycolipid IgG
antibodies were detected in fewer than 50 percent of GBS cases, raising the possibility of direct viral
neurotoxicity. Results of nerve conduction studies were consistent with the acute motor axonal
neuropathy type of GBS; clinical improvement during follow-up suggested reversible conduction failure.
Symptoms of Zika virus infection occurred in 88 percent of patients with GBS; the median interval
between viral syndrome and onset of neurological symptoms was six days. All GBS cases received
intravenous immune globulin, 38 percent required intensive care, and 29 percent needed respiratory care;
all survived. The incidence of GBS during the outbreak was estimated to be 0.24 cases per 1000 Zika
virus infections. (See "Zika virus infection: An overview", section on 'Guillain-Barr syndrome'.)
Cardiovascular disease in inflammatory myopathies (February 2016)
Data are limited regarding the risk of cardiovascular disease in polymyositis (PM) and dermatomyositis
(DM). A large, retrospective, population-based study found a nearly fourfold and threefold increased
incidence of myocardial infarction (MI) among 424 patients and 350 patients with incident PM and DM,
respectively, as compared with those without an inflammatory myopathy, after controlling for relevant risk
factors such as age, sex, glucocorticoids, and nonsteroidal antiinflammatory drugs [12]. The risk of stroke
showed a trend towards an increased risk, but was not statistically significant due to the small number of
outcomes. These findings suggest that monitoring for cardiovascular risk factors is warranted among
patients with DM and PM. (See "Clinical manifestations of dermatomyositis and polymyositis in adults",
section on 'Cardiac disease'.)
NEUROONCOLOGY

Radiation plus temozolomide in patients with 1p19q non-co-deleted anaplastic gliomas (July 2016)
Two previous randomized trials in patients with anaplastic oligodendroglial tumors found that
postoperative treatment with radiation plus PCV (procarbazine, lomustine, and vincristine) improved
survival compared with radiation alone. However, the benefit of PCV was primarily seen in patients whose
tumors contained co-deletion of chromosomes 1p and 19q. The CATNON trial enrolled 748 patients with
newly diagnosed anaplastic gliomas without 1p19q co-deletion and randomly assigned them to one of
four treatment arms: radiation alone, radiation with concurrent temozolomide (TMZ), radiation with
concurrent and 12 cycles of adjuvant TMZ, and radiation with 12 cycles of adjuvant TMZ [13]. In an
interim analysis with a median follow-up of over two years, patients who were randomized to receive 12
cycles of adjuvant TMZ had improved overall survival compared with those who received radiation without
adjuvant TMZ (hazard ratio 0.65). Based on these results, we now recommend radiation plus
chemotherapy in all patients with newly diagnosed anaplastic gliomas, rather than just those with 1p19q
co-deleted tumors. The choice between PCV and TMZ should be individualized based on molecular
characteristics of the tumor and patient preferences. (See "Management of anaplastic oligodendroglial
tumors", section on 'CATNON'.)
Radiation plus temozolomide in older adults with glioblastoma (June 2016)
Shorter courses of radiation are increasingly used to treat older adults with glioblastoma, but the safety
and efficacy of temozolomide in combination with such regimens have not been well studied. In a
multinational phase III trial, 562 adults 65 years of age with a good performance status were randomly
assigned to receive hypofractionated radiation (40 Gy in 15 fractions) plus concurrent and adjuvant
temozolomide or radiation alone [14]. Overall survival was significantly prolonged in patients assigned to
combination therapy (9.3 versus 7.6 months), and quality of life outcomes were similar aside from an
increase in nausea and constipation related to chemotherapy. The addition of temozolomide was
especially beneficial in the subset of patients with O-6-methylguanine-DNA methyltransferase (MGMT)
methylated tumors (13.5 versus 7.7 months). (See "Management of glioblastoma in older adults", section
on 'Efficacy'.)
Valproate not associated with survival benefit in adults with glioblastoma (March 2016)
Several retrospective studies and a small phase II trial in patients with glioblastoma have suggested that
valproate, an antiseizure drug with preclinical evidence of antitumor activity, may improve survival when
given along with radiation. However, a new larger study casts doubt on the utility of valproate in this
setting. In a pooled analysis of >1800 patients enrolled in four large randomized trials for newly diagnosed
glioblastoma, patients taking valproate along with concurrent radiation and temozolomide had no
improvement in progression-free or overall survival compared with those not taking valproate
[15]. Although not examined in this study, other studies have found that valproate may increase
hematologic toxicity associated with temozolomide. Based on these data, preferential use of valproate
over other antiseizure drugs in patients with glioblastoma and seizures does not seem justified outside of
the context of a clinical trial. (See "Experimental treatment approaches for high-grade gliomas", section
on 'Histone deacetylase inhibitors' and "Seizures in patients with primary and metastatic brain tumors",
section on 'Antiseizure drug therapy'.)
Sensitivity of magnetic resonance spectroscopy in IDH-mutant gliomas (February 2016)

Mutations in isocitrate dehydrogenase (IDH) result in the accumulation of 2-hydroxyglutarate (2HG) in

IDH-mutant gliomas. Small studies have shown that 2HG can be detected noninvasively by magnetic
resonance spectroscopy, but the sensitivity of the technique has not been reported. In a study that
included 80 biopsy-confirmed IDH mutant tumors, the sensitivity of spectroscopy for detecting 2HG
ranged from 8 percent in small tumors (<3.4 mL) to 91 percent in large tumors (>8 mL) [16]. Levels of
2HG did not correlate with tumor grade or mitotic index. (See "Clinical presentation and diagnosis of brain
tumors", section on 'Magnetic resonance spectroscopy'.)
PEDIATRIC NEUROLOGY
Botulinum toxin type A for children with spastic cerebral palsy (April 2016)
Botulinum toxin type A (BTX A) is a common treatment for spasticity in children with cerebral palsy (CP);
however, studies to date have been small and have not focused on functional outcomes. In a recent
randomized placebo-controlled trial of 235 children with spastic CP with dynamic equinus foot deformity,
BTX A treatment improved muscle tone and resulted in a modest overall improvement in clinical
status [17]. The growing evidence of successful use of BTX A in children with spastic CP supports the use
of this agent in patients who have increased muscle tone that interferes with function or is likely to lead to
joint contracture with growth. (See"Management and prognosis of cerebral palsy", section on 'Botulinum
toxin'.)
Screening for autism spectrum disorder (March 2016)
Autism spectrum disorder (ASD) is common, with a prevalence of 1 in 50 to 1 in 500 children. Symptoms
of ASD often are present before 18 months of age, but the average age of diagnosis is >4 years. Early
identification is hampered by the heterogeneous presentation and the difficulty of differentiating symptoms
of ASD from those of other developmental disorders. In February 2016, the United States Preventive
Services Task Force concluded that there is insufficient evidence to adequately assess the balance of
benefits and harms of universal screening of children 18 to 30 months of age for ASD [18]. Pending
additional evidence, we continue to suggest universal screening for ASD in children at 18 and 24 months
of age. In our estimation, the potential benefits of early detection outweigh the potential harms of
screening (eg, time, effort, anxiety). (See "Autism spectrum disorder: Surveillance and screening in
primary care", section on 'Our screening recommendations'.)
Stroke prevention in sickle cell disease (March 2016)
Individuals with sickle cell disease (SCD) are at risk for ischemic and hemorrhagic stroke. Transcranial
Doppler (TCD) measures blood flow rate in intracranial arteries and is used to assess stroke risk in
children with SCD. Children with increased TCD velocities are treated with chronic prophylactic
transfusions to reduce the risk of ischemic stroke. The recently published TWiTCH trial
(TCD With Transfusions Changing to Hydroxyurea) randomly assigned 121 children who had completed
a period of chronic transfusions and who met study criteria (related to hemoglobin S levels with
transfusion, TCD velocities, magnetic resonance angiographic findings, ability to comply with treatment
and monitoring, and response to hydroxyurea) to transition to hydroxyurea therapy or to continue
transfusions [19]. After approximately two years of follow-up, TCD velocities were similar in both groups
and there were no strokes in either group. For children who would have met criteria for the TWiTCH trial,

we suggest transitioning to hydroxyurea after two or more years of chronic transfusion, with transfusions
tapered and hydroxyurea dosing gradually increased during the transition, as done in the trial. We
continue to recommend chronic transfusions for all patients with SCD who have had an ischemic stroke
(ie, for secondary prevention). (See "Prevention of stroke (initial or recurrent) in sickle cell disease",
section on 'Chronic transfusion followed by transition to hydroxyurea'.)
OTHER NEUROLOGY
Chronic sleep-wake disturbances after traumatic brain injury (July 2016)
Sleep-wake disturbances are very common in the weeks to months following traumatic brain injury (TBI),
and a new study suggests that many of these symptoms persist long term. In a prospective case-control
study in which 31 patients with TBI of any severity were evaluated at 18 months after injury, 67 percent of
patients had evidence of excessive daytime sleepiness on objective testing, compared with only 19
percent of healthy controls [20]. Patients also had persistent pleiosomnia (increased need for sleep),
requiring an average of one more hour of sleep per 24 hours than controls. As in earlier studies, patients
tended to underestimate their symptoms, emphasizing the importance of both subjective and
objective sleep testing in patients with sleep-wake complaints after TBI. (See "Sleep-wake disorders in
patients with traumatic brain injury", section on 'Natural history'.)
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REFERENCES
1.

Amarenco P, Lavalle PC, Labreuche J, et al. One-Year Risk of Stroke after Transient Ischemic
Attack or Minor Stroke. N Engl J Med 2016; 374:1533.

2.

Howard G, Roubin GS, Jansen O, et al. Association between age and risk of stroke or death from
carotid endarterectomy and carotid stenting: a meta-analysis of pooled patient data from four randomised
trials. Lancet 2016; 387:1305.

3.

Rosenfield K, Matsumura JS, Chaturvedi S, et al. Randomized Trial of Stent versus Surgery for
Asymptomatic Carotid Stenosis. N Engl J Med 2016; 374:1011.

4.

Gomm W, von Holt K, Thom F, et al. Association of Proton Pump Inhibitors With Risk of
Dementia: A Pharmacoepidemiological Claims Data Analysis. JAMA Neurol 2016; 73:410.

5.

Satizabal CL, Beiser AS, Chouraki V, et al. Incidence of Dementia over Three Decades in the
Framingham Heart Study. N Engl J Med 2016; 374:523.

6.

FDA approves Zinbryta to treat multiple sclerosis.

www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm504000.htm (Accessed on June 09,
2016).

7.

Bagnall RD, Crompton DE, Petrovski S, et al. Exome-based analysis of cardiac arrhythmia,
respiratory control, and epilepsy genes in sudden unexpected death in epilepsy. Ann Neurol 2016;
79:522.

8.

Klein P, Schiemann J, Sperling MR, et al. A randomized, double-blind, placebo-controlled,

multicenter, parallel-group study to evaluate the efficacy and safety of adjunctive brivaracetam in adult
patients with uncontrolled partial-onset seizures. Epilepsia 2015; 56:1890.

9.

http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/205836Orig1s000,205837Orig1s000,
205838Orig1s000lbl.pdf (Accessed on March 09, 2016).

10.

Navarro V, Dagron C, Elie C, et al. Prehospital treatment with levetiracetam plus clonazepam or
placebo plus clonazepam in status epilepticus (SAMUKeppra): a randomised, double-blind, phase 3 trial.
Lancet Neurol 2016; 15:47.

11.

Cao-Lormeau VM, Blake A, Mons S, et al. Guillain-Barr Syndrome outbreak associated with Zika
virus infection in French Polynesia: a case-control study. Lancet 2016; 387:1531.

12.

Rai SK, Choi HK, Sayre EC, Avia-Zubieta JA. Risk of myocardial infarction and ischaemic stroke
in adults with polymyositis and dermatomyositis: a general population-based study. Rheumatology
(Oxford) 2016; 55:461.

13.

van den Bent MJ, Erridge S, Vogelbaum MA, et al. Results of the interim analysis of the EORTC
randomized phase III CATNON trial on concurrent and adjuvant temozolomide in anaplastic glioma
without 1p/19q co-deletion: An Intergroup trial. J Clin Oncol 2016; 34 (suppl):abstract LBA2000.

14.

Perry JR, Laperriere N, O'Callaghan CJ, et al. A phase III randomized controlled trial of shortcourse radiotherapy with or without concomitant and adjuvant temozolomide in elderly patients with
glioblastoma. J Clin Oncol 2016; 34:suppl (Abstract # LBA2).

15.

Happold C, Gorlia T, Chinot O, et al. Does Valproic Acid or Levetiracetam Improve Survival in
Glioblastoma? A Pooled Analysis of Prospective Clinical Trials in Newly Diagnosed Glioblastoma. J Clin
Oncol 2016; 34:731.

16.

de la Fuente MI, Young RJ, Rubel J, et al. Integration of 2-hydroxyglutarate-proton magnetic

resonance spectroscopy into clinical practice for disease monitoring in isocitrate dehydrogenase-mutant
glioma. Neuro Oncol 2016; 18:283.

17.

Delgado MR, Tilton A, Russman B, et al. AbobotulinumtoxinA for Equinus Foot Deformity in
Cerebral Palsy: A Randomized Controlled Trial. Pediatrics 2016; 137:e20152830.

18.

Siu AL, US Preventive Services Task Force (USPSTF), Bibbins-Domingo K, et al. Screening for
Autism Spectrum Disorder in Young Children: US Preventive Services Task Force Recommendation
Statement. JAMA 2016; 315:691.

19.

Ware RE, Davis BR, Schultz WH, et al. Hydroxycarbamide versus chronic transfusion for
maintenance of transcranial doppler flow velocities in children with sickle cell anaemia-TCD With
Transfusions Changing to Hydroxyurea (TWiTCH): a multicentre, open-label, phase 3, non-inferiority trial.
Lancet 2016; 387:661.

20.

Imbach LL, Bchele F, Valko PO, et al. Sleep-wake disorders persist 18 months after traumatic
brain injury but remain underrecognized. Neurology 2016; 86:1945.
Topic 8362 Version 6609.0

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