INTRODUCTION

 

Migraine is a common neurovascular disorder characterized by severe episodes of headache and autonomic-neurological symptoms.¹

Visual symptoms and photophobia are common features of migraine, but are not exclusively confined to attacks.

Hypersensitivity to environmental light has been demonstrated to persist even between attacks², and visual stimulus can precipitate the migraine attacks.³ Moreover, the aura in migraine is usually visual in 80–90% of cases.⁴ Therefore, it is suggested that visual system may play a role in the pathophysiology of migraine.³

Previous studies showed visual evoked potential changes between migraineurs and normal subjects, but results were often conflicting. In the headache free interval, some authors showed difference of amplitude or latencies of P100 between migraineurs and healthy control subjects; others did not show any difference.^1,4-7

Aim of work: To compare VEP (P100) in patients with migraine with and without aura to normal subjects, and the effect of prophylactic treatment on VEP.

 

SUBJECTS AND METHODS

 

The present study included 32 patients with migraine, presented to neurology clinic at a regional hospital, KSA, during the period from June 2012 to May 2013 with age range from 19 to 54 years (27 females and 5 males) and 15 sex and age matched control subjects.  The diagnosis of migraine was in accordance with the International Headache Society  (IHS) classification.⁸ Migraine patients with ocular disorders or other neurological diseases were excluded from the study.

Patients were recorded in the headache-free interval; at least 72 hours before or after an attack. Patients were informed to contact us if attack occurred within 72 hours after the test, and the test was repeated. Recordings were performed in a quiet room with dimmed light, patients seated in an armchair, 1 minute in front of a television monitor (mean luminance 240 cd/m2). Stimuli were presented as a checkerboard pattern of black and white squares subtending 4° 0.5’ of arc (contrast 100%) at a reversal frequency of 3 Hz. With one eye patched, subjects were instructed to fixate on a point in the middle of the screen. VEPs were recorded with silver-silver chloride electrodes applied to the scalp. A standard transverse chain of three electrodes was sited at 5 cm above the inion (MO), while one electrode was placed on the midline and one on each side at an inter-electrode distance of 5cm (LO and RO). All electrodes were referred to a common mid-frontal electrode 12 cm above the nasion. During uninterrupted stimulation, sequential blocks of 100 responses were averaged for a total duration of 9 min. We studied the amplitudes and latencies of the P100 (peak latency of the point of maximal positivity (Pl00) and amplitude measured from the preceding negative peak (N75) to trough of the Pl00).

 

Statistical Analysis

SPSS software (Version 11.0) was used for statistical evaluation. Analysis of variance with repeated measures (ANOVA) was performed to compare P100 amplitude and latency between patients’ subgroups and control subjects. Post hoc analysis was done by using paired t-test with Bonferroni corrections. Age of patients and control subjects, and P100 parameters between right and left eye were compared using paired T-tests. The Pearson correlation analysis was used to determine the correlation between duration of migraine and P100 parameters.

 

RESULTS

 

The present study included 32 patients with migraine with mean age of 31±8.9. Twenty-seven (84.4%) of our patients were females, and 5 (15.6 %) were males.

Fifteen patients had migraine with visual aura (MA) 13 of them were female, and 17 patients diagnosed as migraine without aura (MO) 14 of them were female.

No significant difference (P=0.378) was present between age of patients with migraine with aura (30.3±6), and those with migraine without aura (33±10.8).

The mean disease duration was 28.8±12.3 months for migraine with aura, and for migraine without aura, it was 31.8±14.9 months. There was no significant difference (P=0.543) regarding the disease duration between the two groups. Migraine without aura

 

Fourteen migraineurs, 6 migraine without aura (MO) and 8 migraine with aura (MA), had a prophylactic migraine treatment and 18 (11 MO and 7 MA) had no prophylactic therapy. The drugs used were: beta blockers, antiepileptic drugs (topiramate), 5-HT receptor antagonists (pizotifen), calcium channel blockers (flunarizine) and antidepressants (amitriptyline), and treatment was effective regarding severity and frequency of headache

We studied the amplitudes and latencies of the P100 component of the VEP. We first compared VEP latencies and amplitudes between the right and the left eyes within each population. Because t-test revealed non-significant differences between the two eyes, we subsequently calculated mean values from both eyes for each subject.

The amplitude of P100 component was significantly higher (P<0.001) in patients with migraine (11.4±1.3) than control subjects (9.7±0.9). This significant difference still present in patients subgroup with aura 11.7±1.4 (P<0.001) and without aura 11.1±1.2 (P<0.01) compared to control subjects; (Table 1). The significant difference disappeared (P=0.164) in patients on regular prophylactic treatment (10.5±0.9) compared to healthy subjects (Table 2).

Regarding the latency of P100, it was significantly (P<0.01) longer in patients (103.7±4.7) than control (100.3±3.2) groups. Patients with migraine with aura (105.2±4.8) had significantly (P<0.01) longer P100 latency compared to control subject while the difference was not significant (P=0.517) between patients with migraine without aura (102.3±4.3) compared to control subjects. This difference disappeared in patients with regular prophylactic treatment (Tables 1 and 2).

There was no correlation between age of the patients, or the duration of migraine and the P100 amplitude (Figure 1) or latency (Figure 2) in patients with migraine and in patient's subgroups (all of them: p>0.05).

Table 1. P100 parameters in migraine subgroups compared to control subjects.

 

	MA (n =15)		MO (n =17)		Control (n =15)
	Mean	±SD	Mean	±SD	Mean	±SD
P100 latency (ms)	105.2*	4.8	102.3	4.3	100.3	3.2
P100 amplitude (µv)	11.7**	1.4	11.1*	1.2	9.7	0.9

MA Migraine with aura, MO Migraine without aura,

* Significant at P <0.05 ** Significant at P <0.01

Table 2. P100 parameters in patients with and without prophylactic treatment compared to control subjects.

 

	Prophylactic treatment (n =14 )		No prophylactic treatment (n =18)		Control (n =15)
	Mean	±SD	Mean	±SD	Mean	±SD
P100 latency (ms)	100.8	4.2	105.9*	3.8	100.3	3.2
P100 amplitude (µv)	10.5	0.9	12*	1.1	9.7	0.9

* Significant at P <0.01

 

 

 

Figure 1.               Correlation between disease duration, and P100 amplitude in patients with migraine.

 

 

 

Figure 2.               Correlation between disease duration, and P100 latency in patients with migraine.

 

DISCUSSION

 

This study was planned to compare VEP (P100) in migraine patients - with and without aura - to normal subjects, and the effect of prophylactic treatment on VEP.

We found high P100 amplitude in patients with migraine either with or without aura compared to controls; however, the amplitude of P100 was normal in patients with migraine with regular prophylactic treatment. The latency of P100 was delayed in patients with migraine with aura, but it was normal in patients with migraine without aura, and patients on regular prophylactic treatment.

There was no correlation between P100 parameters (amplitude, and latency) and disease duration, and age of the patients in any of patient's subgroups. In accordance with our findings, higher P100 amplitude was reported in many previous studies either in children or in adult patients with migraine either with or without aura.^9-14

Shibata and colleagues (1997, and 1998) reported higher P100 amplitude in patients with migraine than control subject, especially on the contralateral side of the visual aura independent on duration or severity of the illness.^{7, 15}

On the other hand, Khalil and colleagues (2000) reported high P100 amplitude in patients with migraine without aura of any duration of the disease, and migraine with aura of short duration (less than 10 years), the amplitude decline in patients with migraine with aura of long duration.¹⁴ More recently, Unay and colleagues (2008) reported similar tendency with significantly higher P100 amplitude in children with migraine compared to healthy subjects, and patients with tension type headache.³

Prolonged P100 latency in patients with migraine had been reported by several previous studies.^3,13,14,16

However, Spreafico and colleagues (2004) reported short P100 latency in patients with migraine compared to control subjects, and it was  normal in patients  on prophylactic treatment,  he suggested that a different responsiveness of the visual system in migraineurs due to a dysmodulation of sensor input, leading to facilitation of visual processing.⁴

The absence of correlation between disease duration and age of the patients on one hand, and the P100 parameters on the other hand was in accordance with many previous studies.^3,7,11,15 However, Khalil and colleagues (2000), reported a decline in P100 amplitude in patients with migraine with aura of more than 30 years duration, but there was no correlation between P100 parameters and disease duration in patients with migraine without aura (of any duration) and migraine with aura of less than 10 years duration. they concluded that, the low amplitude in migraine with aura of prolonged duration is an acquired phenomenon, related to the events of the aura.¹⁴ The results were similar to our results especially with disease duration of less than 10 years.  

Abnormalities in VEP strengthen the idea of hyperexcitability of the brain, which is consistent with previous studies in migraine patients. In previous studies it was claimed that neuronal hyperexcitability in migraine patients leads to increased sensitivity to light and other stimuli, so that light discomfort could emerge in headache-free periods.¹⁷ Chronicle and Mulleners (1994) stated that migraine attacks with or without drug treatment induces interneuron losses (loss of inhibitory inter-neuron) in the visual cortex, leading to hyperexcitability.¹⁸ Hyperexcitability status, which can be  confirmed with electrophysiological studies, can explain the basis of VEP response abnormalities.¹⁷ It has been suggested that this input modulation mechanism (lack of inhibition or increase in excitation) may occur at any point in the visual pathway.¹²

Prolonged P100 latency in these patients cannot be interpreted with one factor. Some authors noted that recurrent cerebral edema and ischemia cause latency prolongation provoking demyelination and neuronal hyperexcitability. Increased stroke incidence in migraine patients strengthens the role of ischemia in the pathophysiology of migraine.^1,3 It has also been postulated that these electrophysiologic abnormalities can be related to a central neurotransmitter alteration involving the input modulation mechanism, such as lack of inhibition or increase in excitation. Another hypothesis implies an instability of the neural control of cerebral vascular supply, predisposing the individual to transient episodes of lateralized cortical oligemia.¹⁴ 

In this study, prophylactic treatment associated with normalization of P100 parameters.

In recent years many studies investigated electrophysiological parameters in migraine.¹⁹ Following beta-blocker treatment amplitudes and latencies of pattern reversal visual evoked potentials were reported to normalize.²⁰ Also in the study of Gerwig and colleagues (2012), in patients with prophylactic (Beta-blocker) treatment, the mean Phosphene threshold (PT) increased to values corresponding to that in healthy controls as assessed by transcranial magnetic stimulation (TMS).²¹ At the same time, topiramate treatment²², and valporic acid treatment²³,  had the same effect on PT studied by TMS.

These findings suggest that prophylactic treatment in migraine may reduce the excitability of the visual cortex.

Consistent with earlier findings, the data suggest that modified central excitability may be one factor of prophylactic efficacy in migraine and that dysfunction of cortical excitability is at least associated with mechanisms underlying the pathophysiology of migraine.

 

Conclusion

Visual evoked potential (P100) is abnormal in patients with migraine with or without aura, and it is normal in patients with migraine with regular prophylactic treatment. It has been suggested that modified cortical excitability may be one factor of prophylactic efficacy in migraine and that its dysfunction is at least associated with mechanisms underlying the pathophysiology of migraine.

 

[Disclosure: Authors report no conflict of interest]

 

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