This case indicates that the pathophysiology of migraine and epilepsy may involve bidirectional crosstalk, and the symptoms of one may modify the symptoms of the other. In addition, lomerizine hydrochloride may modify the process of both migraine and epilepsy.
The pathophysiological relationship between migraine and epilepsy has long been discussed clinically. Our patient required careful consideration because she presented with various symptoms of both migraine and epilepsy. Her initial symptom was epilepsy at the age of 3 years, which indicates that she has a seizure disorder. Since the age of 17 years, she presented with migraine with typical aura, which was often prolonged and associated with aphasia. Later, at the age of 25 years, migraine aura was followed by loss of consciousness and urinary incontinence, and even generalized tonic-clonic seizures occurred. Epilepsy and migraine with aura became a series of symptoms when the visual symptoms became shorter in duration. No changes in migraine-like headaches occurred after the change in the preceding visual symptoms. Our provisional diagnosis at the time of her initial visit was “migraine aura-triggered seizure” according to ICHD-3. However, unique features of this patient are the change in the pattern of the prodromal symptoms and also seizures with urinary incontinence following the headaches. Neurological symptoms preceding the headaches changed from the usual typical aura to a short-lasting aura, which included complaints of deja-vu scenery, a common feature of epileptic hallucinations that usually helps distinguish epilepsy from migraines .
Both migraine and epilepsy are associated with brain hyperexcitability, with migraine being initiated by cortical spreading depression (CSD). Pathophysiologically, migraine, and epilepsy do not occur simultaneously, but clinical observation of our patient suggested that they may occur sequentially in migraine aura-triggered seizure . Seizures may trigger trigeminovascular pain mechanisms, as migraine is triggered by CSD . One theory for migraine is the central sensitization mechanism. This theory proposes altered processing of sensory input in the brainstem, principally the trigeminal nucleus caudalis . Recent research has suggested the possibility of a similar mechanism for headache in epilepsy .
Lomerizine hydrochloride was effective for this patient and may have been effective both for migraine and epilepsy. After administration of lomerizine hydrochloride, the first headache attack followed by loss of consciousness and urinary incontinence did not occur until 1.5 years later, and the frequency of headaches due to either migraine or epilepsy decreased significantly from once a month to twice a year. Lomerizine hydrochloride is a voltage-dependent L- and T-type Ca2+ channel blocker that crosses the BBB and is recommended as one of the first-choice drugs for migraine prevention in the Clinical Practice Guideline for Chronic Headache 2013 by the Japanese Society of Neurology . Lomerizine hydrochloride belongs to the same class of diphenylpiperazine-type Ca2+ channel antagonists as flunarizine hydrochloride, which was withdrawn by the government of many countries because of the adverse events of parkinsonism . Lomerizine hydrochloride, which was developed to replace flunarizine hydrochloride, inhibits cortical hypoperfusion and expression of c-Fos-like immunoreactivity induced by spreading depression in rats. This activity of lomerizine hydrochloride is mediated by blockade of Ca2+ entry, preventing excessive Ca2+ influx into neural cells . Lomerizine hydrochloride may inhibit CSD in migraine. Lomerizine hydrochloride 10 mg daily reduces the frequency and severity of migraine attacks after 8 weeks in 64% of patients , and adverse events are similar to placebo, indicating the safety of the drug. Moreover, flunarizine hydrochloride was reported to have some effect for the treatment of epilepsy . Our experience lends support to the tenet that lomerizine hydrochloride may be efficacious in alleviating migraine and epilepsy by suppressing brain hyperreactivity.