PATTERN REVERSAL VISUAL EVOKED POTENTIALS AND EEG IN MIGRAINE PATIENTS WITH- AND WITHOUT VISUAL AURA

Journal of Neurological Sciences (Turkish)

Table of Contents

NOROL BIL D 18: 1 , 2001 http://www.med.ege.edu.tr/norolbil/2001/NBD14401.html

Research Article

PATTERN REVERSAL VISUAL EVOKED POTENTIALS AND EEG IN MIGRAINE PATIENTS WITH- AND WITHOUT VISUAL AURA*
Aysun SOYSAL, Turan ATAY, Fikret AYSAL, Musa OZTURK, Yavuz ALTUNKAYNAK, Sevim BAYBAS, Baki ARPACI

Bakirkoy State Hospital for Neurological & Psychiatric Diseases, Departments of Neurology I-II, Istanbul, Turkey

ABSTRACT
In order to investigate possible electrophysiological changes in migraine, we evaluated pattern reversal visual evoked potentials (PRVEP) and EEG findings of 13 patients with visual aura (MWA) and 20 patients without visual aura (MWOA) during interictal period as well as in a control group of 21 normal subjects. When compared with the controls, the P100 latencies of PRVEPs aroused by full-field, right- and left hemi-field stimulation of both eyes were significantly longer in MWOA patients in all recording electrodes. Similarly, the P100 latencies of PRVEPs in MWA patients were also significantly longer than those of controls except for O2 recordings with left hemi-field stimulation, and O1/O2/Oz recordings with full-field stimulation of right eye. On the other hand, EEG abnormalities were observed in only one of MWA and in three of MWOA patients. Although controversial results have been reported in the literature, our results suggest that there is a neuronal dysfunction in migraine which can be elicited with VEP studies.

Key-words: Migraine, visual evoked potentials, EEG. INTRODUCTION

It has been postulated that local ischemia due to focal cerebral vasospasm is responsible for the prodromal neurologic deficits in migraine patients(1,5,15,16,17). Cerebral blood flow (CBF) studies in patients having migraine with aura (MWA) have shown a reduction of regional CBF in one occipital pole during or just before the aura (1, 5,17). The reduction of regional CBF spreads forward at a rate of 2 to 3 mm per minute or may stop at a point and it is correlated with the
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symptoms of migraine (1, 5,17). It has been reported that the reduction of CBF is limited to occipital regions in patients with pure visual aura whereas more widespread CBF reduction may also cause symptoms in extremities (17). Migraine without aura (MWOA) is accompanied by a 20% or less reduction of CBF. More severe reduction of CBF (i.e. 50% or more) may lead to MWA (15,16,17). The CBF changes in migraine is very similar to " cortical spreading depression (SD)" observed by Leao in animal studies (1,5,15,16,17). This phenomenon can be elicited in experimental animals by stimulation of cerebral cortex, and consists of a slow wave of depolarization followed by repolarization. Temporary abolishment of the EEG and changes in cortical pH also occur. The process is reversible and spreads at a rate of 2 to 4 mm per minute (1, 5,17). The similarity between the SD described by Leao and CBF changes in migraine have led to the hypothesis that migraine may have a physiological basis in form of a SD (12). Visual evoked potentials (VEP) recorded at the scalp are caused by the activation of occipital neurons and represents the summation of dendritic synaptic potentials of these neurones (4). Therefore, VEP studies have commonly been performed in migraine cases. On the other hand, there are some studies in the literature suggesting hyperexcitability in occipital areas (8). In order to investigate possible electrophysiological changes in migraine, we evaluated pattern reversal visual evoked potentials (PRVEP) and EEG findings in migraine patients with- and without visual aura as well as in a healthy control group.

MATERIALS and METHODS

Thirty-three migraine patients assembled from the Headache Outpatient Clinic of Bakirkoy State Hospital for Neurological & Psychiatric Diseases, Departments of Neurology I-II, and 21 age-matched healthy volunteers were included in the study. Out of 33 patients, 13 had visual aura (MWA). The diagnosis was made according to the classification proposed by the International Headache Society (11). The mean age of MWA-, MWOA- and control group was 33.9 9.28 (18-50), 37.9 10.5 (20-57) and 36.4 9.22 (22-54), respectively. All patients and controls were female and none of the patients was in migraine attack during the study. Neurological and ophtalmological examinations were normal in both patients and controls. The duration of the disease was 1-25 and 1-30 years in MWA and MWOA group, respectively. The frequency of attacks was 1-4/month in both groups. The duration of the attacks was 12-60 hours in MWA and 6-60 hours in MWOA group. All patients included in the study had their last migraine attack at least one week prior to the EEG and VEP recordings, and they were still under prophylactic therapy. EEG and VEP recordings were made on the same day for each patient. EEG recordings along with hyperventilation and photic stimulation were performed using a 24+8 channel Medelec (Profile) device. Different montages were evaluated. VEP studies were performed using a Medelec Sapphire 4ME device. Ag/AgCl disc electrodes were used. Active electrodes were placed to O1, O2 and Oz (according to 10-20 system), and referred to Fz. Electrode impedance was kept below 2 k. The filter bandpass was 1-50 Hz. Pattern reverse stimulation was performed in a dark room by a 16x16 checkerboard pattern 70 cm away from the nasion with 2 Hz frequency and 100% contrast. Full-field, right and left hemi-field pattern reverse stimuli were consecutively given to the right- and left eye. At least 100 artefact-free responses were averaged and two runs were performed for each patient. The P100 latencies and the peak to peak N75/P100 amplitudes of VEP were measured. Results were compared with students t-test.

RESULTS
No statistical difference was found between MWA- and MWOA patients and control group in respect to the mean age (p=0.704 and p=0.380, respectively). One patient with MWA- and another one in MWOA group exhibited mild slowing in EEG activity on frontal areas. One patient in MWOA group showed theta activities on the left frontal region, while another one had slow wave paroxysms on the left hemisphere.

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The P100 latencies and amplitudes of VEP studies are summarized in Tables I, II, III and IV. When compared with the controls, the P100 latencies of PRVEPs aroused by full-field, right- and left hemi-field stimulation of both eyes were significantly longer in MWOA patients in all recording electrodes. Similarly, the P100 latencies of PRVEPs in MWA patients were also significantly longer than those of controls except for O2 recordings with left hemi-field stimulation and O1/O2/Oz recordings with full-field stimulation of right eye. Although not statistically significant, the amplitudes of VEPs in both MWA- and MWOA groups were also found to be slightly higher than those of controls.

Table I. The P100 latencies of VEP responses after left eye stimulation
MWA MWOA CONTROLS

Full-field stimulation O1 O2 Oz Left hemi-field stimulation O1 O2 Oz Right hemi-field stimulation O1 O2 Oz 109.3 9.7 110.6 9.9~ 110.4 10.4 108.3 8.4* 107.2 8.0~ 107.6 7.9~ 100.1 6.6 100.5 5.1 100.8 5.1 109.5 12.2 108.9 14.7 108.9 12.5 107.1 8.3 107.3 9.3~ 107.3 8.1~ 100.8 4.7 99.1 7.0 100.4 5.0 107.6 11.4 108.0 11.1 107.8 10.8 107.4 7.2* 107.8 8.1* 107.6 7.4* 99.1 5.6 99.7 6.2 100.2 4.7

*p<=0.001 ~p<0.005 p<0.01 p<0.05

Table II. The P100 latencies of VEP responses after right eye stimulation MWA MWOA CONTROLS

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Full-field stimulation O1 O2 Oz Left hemi-field stimulation O1 O2 Oz Right hemi-field stimulation O1 O2 Oz 105.8 10.8 106.9 10.3 107.1 11.1 108.0 8.1* 107.2 8.6~ 106.9 7.8~ 98.1 6.4 99.8 5.1 99.9 5.7 107.4 9.3 106.7 10.9 108.6 10.4 106.0 7.7 107.3 9.2 107.4 7.8 100.6 4.2 100.6 6.1 101.5 4.5 105.8 9.3 106.0 9.7 107.1 10 105.8 8.0 106.9 8.2 106.7 8.1 100.4 6.8 101.1 7.2 101.1 6.0

*p<=0.001 ~p<0.005 p<0.01 f p<0.05

Table III. The N75/P100 amplitudes of VEP responses after left eye stimulation

MWA Full-field stimulation O1 O2 Oz Left hemi-field stimulation O1 O2 Oz 6.75 2.5 6.41 2.0 8.74 3.1 7.97 3.5 8.07 2.9 10.6 4.3

MWOA

CONTROLS

6.76 2.4 6.86 3.0 9.06 3.0

5.68 2.3 6.00 2.2 8.41 3.1

5.29 1.5 5.23 1.4 6.87 1.9

5.42 2.4 5.38 1.7 7.09 2.5

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Right hemi-field stimulation O1 O2 Oz 6.76 3.1 6.81 2.4 8.27 3.1 5.26 1.6 5.78 1.7 6.82 1.8 5.08 1.7 5.97 2.3 7.03 2.4

Table IV. The N75/P100 amplitudes of VEP responses after right eye stimulation

MWA Full-field stimulation O1 O2 Oz Left hemi-field stimulation O1 O2 Oz Right hemi-field stimulation O1 O2 Oz 6.33 2.6 6.93 2.6 8.23 2.7 6.68 2.7 6.02 2.0 8.52 3.3 7.64 3.1 7.78 2.3 10.27 3.8

MWOA

CONTROLS

6.38 2.1 6.77 2.8 8.93 3.3

6.12 2.7 6.39 2.4 8.60 2.9

5.62 2.0 5.31 1.7 7.03 2.3

5.20 2.1 5.40 1.8 7.05 2.5

5.33 1.5 5.84 1.8 6.94 1.8

4.88 1.8 5.85 1.9 6.85 1.9

DISCUSSION
Our study demonstrated that the P100 latencies of VEP (LP100) responses in both MWA and MWOA group were longer than those of control group, whereas no significant difference was found in respect to the amplitudes. The findings reported in several studies are controversial. Using flash stimulation, in two different studies, Lehtonen found increased amplitudes and LP100 of VEP responses (20). Similar to our study, Kennard reported increased LP100 and higher VEP amplitudes with PR stimulation, and postulated that repeated episodes of ischemia and cerebral edema could provoke demyelination of visual pathways (20). Another study, however, demonstrated that subjects with stabilized sequelae of posterior cerebral infarction presented usually normal VEP responses, whereas variable responses were obtained after separate

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stimulation of the hemifield (19). Connolly et al. reported increased amplitudes of VEP responses in migraine patients, and the authors suggested that this finding might reflect occipital hyperexitability (6). Polich reported a statistically unsignificant increase in LP100 and VEP amplitudes compared with the controls (13). Mariani found significantly longer LP100 in MWA but normal LP100 and VEP amplitudes in MWOA (13). Nyrkes study showed an interhemispheric asymmetry in classic migraineurs and postulated that the changes may reflect increased functional lability of the occipital visual cortex (14). Diener reported that the use of -blockers resulted in a significant decrease in VEP amplitudes in migraine patients (7). Some other studies demonstrated no difference in VEP latencies and amplitudes of migraineurs compared with the controls (9, 20, 21). Some authors reported decreased magnesium (Mg) serum levels and increased VEP amplitudes in migraine patients (3,10,18,22). After Mg treatment, VEP amplitudes and/or the frequency of migraine attacks were decreased (3,10). These data seem to suggest that low brain Mg level and higher VEP amplitudes can both be an expression of neuronal hyperexitability of the visual pathways and a lowered threshold for migraine attacks. On the other hand, fra et al. demonstrated that during long period of PRVEP, the amplitudes of VEP responses were progressively decreased in control subjects, but remained stable in both MWA and MWOA group (2). The authors postulated that these findings represented an interictal habituation deficit in cortical information processing which might suggest a lactate accumulation in sensory cortex. It has been suggested that there is an occipital hyperexitability, as photic stimulation provokes paroxysmal responses in epileptic patients and visual signs in migraineurs (8). In our study, only one patient in MWOA group exhibited paroxysmal activity suggesting neuronal hyperexitability in migraine. EEG changes in other three patients were considered as non-specific. Epileptic photosensitivity and migraine with visual aura could share some common pathophysiological features. It has been postulated that primary events in migraine are in CNS but the vascular phenomena are secondary. Considering the hypothesis about the SD in migraine, neuronal hyperexitability may provoke both the migraine- and epileptic attacks (8). Our study demonstrated significant changes in VEP latencies. Controversial results reported in the literature may be explained by using of different stimulation procedures and study protocols. Whatever the underlying etiology, our results suggest that there is a neuronal dysfunction in migraine which can be elicited with VEP studies.

GRSEL AURASI OLAN VE OLMAYAN MGRENL HASTALARDA PATERN-REVERS GRSEL UYARILMI POTANSYELLER VE EEG*

ZET
Migrendeki olas elektrofizyolojik deiiklikleri incelemek iin, grsel auras olan (GA) 13 ve grsel auras olmayan (GAO) 20 migrenli hasta ile 21 normal kiiden oluan kontrol grubunda, interiktal dnemde pattern-revers grsel uyarlm potansiyel (PRGUP) yantlar ve EEG bulgular incelendi. Kontrollarla kyaslandnda, GAO migrenli hastalarda tam alan, sa ve sol yar alan uyarm ile tm kayt elektrodlarndan elde edilen PRGUP yantlarnn P100 latanslar uzundu. Benzer ekilde GAl migrenli hastalarda da P100 latanslar, sol yar alan uyarm ile O2 ve sa gzn tam alan uyarm ile O1/O2/Ozden kaydedilen PRGUP yantlar dnda kontrollerden anlaml olarak uzun bulundu. GAl bir hastada ve GAO hastada EEG bozukluklar saptand. Literatrde elikili sonular bildirilmesine ramen, sonularmz migrende GUP almalar ile ortaya karlabilen nronal fonksiyon bozukluu olduunu dndrmtr. Anahtar kelimeler: Migren, grsel uyarlm potansiyeller, EEG.

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*Presented in "XI. International Congress of EMG and Clinical Neurophysiology", Sept.7-11,1999, Prague,Czech Rep.

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17. Olsen TS. Migraine with and without aura: The same disease due to cerebral vasospasm of different intensity. A hypothesis based on CBF studies during migraine. Headache 1990; 30: 269 72. 18. Ramadan NM, Halvorson H, Vanda-Linde A, Levine SR, Helpern JA, Welch KMA. Low brain magnesium in migraine. Headache 1989; 29: 590-3. (Medline abstract) 19. Streletz LJ, Bae SH, Roeshman AM, Shatz NJ, Savino PJ. Visual evoked potentials in occipital lesions. Arch Neurol 1981; 38: 80-5. (Medline abstract) 20. ener H, Haktanir I, Demirci S. Pattern-reversal visual evoked potentials in migraineurs with or without visual aura. Headache 1997; 37: 449-51. 21. vanDijk JG, Dorresteijn M, Haan J, Ferrari MD. No confirmation of visual evoked potential diagnostic test for migraine. Lancet 1991; 337: 517-18. 22. Welch KMA, DAndrea G, Tepley N, Barkley G, Ramadan NM. The concept of migraine as a state of central neuronal hyperexcitability. In : The neurologic clinics of North America. Headache. Ed, Mathew NT. Philadelphia, W.B. Saunders Company, 1990, pp : 817-28.

Correspondence Dr. Aysun Soysal Bakrky Ruh ve Sinir Hastalklar Hastanesi 1. Nroloji Klinii 34747 Bakrky/Istanbul TRKYE Phone :+90-212-543 65 65/423 Fax : +90-212-572 9595 E-mail ayssoysal@isnet.net.tr The Online Journal of Neurological Sciences (Turkish) 1984-2001

Received by: 19.01.2001 Accepted : 21.02.2001 Peer-reviewers: 3 Top of the page

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