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Migralepsy: Is the Current Deﬁnition Too Narrow?
Ferdinando Maggioni, MD; Edoardo Mampreso, MD; Silvia Ruffatti, MD; Federica Viaro, MD; Viviana Lunardelli, MD; Giorgio Zanchin, MD
The relationship between epilepsy and migraine is complex and remains to be determined. We report 3 cases that address 2 questions on this topic. The ﬁrst and second cases showed an association between migraine without aura and the onset of epileptic seizures. The third case report describes a patient in whom migraine with aura occurred and was followed by the development of status epilepticus, which occurred 2 or 3 hours after the attack of migraine with aura. We discuss the present deﬁnition of migralepsy and reassess its deﬁnition by suggesting possible extensions to its current deﬁnition. Key words: migraine without aura, migraine with aura, epilepsy, status epilepticus, migralepsy
The clinically based hypothesis that migraine and epilepsy are related dates back to the 19th century.1,2 At present, these 2 disorders are considered 2 paroxysmal diseases that display epidemiological and clinical comorbidity.1 The prevalence of epilepsy in a population of migraine sufferers ranges between 1% and 17% with a median of 5.9%3 and this prevalence is conspicuously higher than the 0.5% prevalence of epilepsy that is found in the general population.4 The prevalence of migraine in patients with epilepsy is high and ranges between 8.4% and 20%.1 Headache develops very frequently after an epileptic seizure but it is rare that a migraine attack triggered an epileptic seizure (1.7-3%).5,6 This phenomenon, deﬁned as “migralepsy,” is codiﬁed in International Classiﬁcation of Headache Disorders II (ICHD-II), 1.5.5 (IHS, 2004).7 According to ICHD-II, the diagnosis of migralepsy should fulﬁll 2 diagnostic criteria: 1. Migraine fulﬁlling criteria for 1.2 Migraine with aura (MA). 2. A seizure fulﬁlling diagnostic criteria for 1 type of epileptic attack occurs during or within one hour after a migraine aura. The other known associations between headache and epilepsy are also included in ICHD-II and are called Hemicrania epileptica 7.6.1 and Post-ictal headache 220.127.116.11
From the University of Padua—Department of Neurosciences, Padova, Italy (F. Maggioni, E. Mampreso, S. Ruffatti, F. Viaro, V. Lunardelli); University Headache Center, UCADH— Department of Neurosciences, Padova, Italy (G. Zanchin). Address all correspondence to F. Maggioni, University of Padua—Department of Neurosciences, Via Giustiniani 5, 35128 Padova, Italy. Accepted for publication January 22, 2008.
In this communication, we report 3 cases. In 2 cases, the seizures were triggered by a migraine without aura (MO). In the third case, we describe a patient in which an MA attack resulted in the development of status epilepticus, and in which the seizures developed more than one hour after the attack of MA.
CASE REPORTS Case One.—A 32-year-old woman shop assistant presented with a history of MO and epilepsy. The patient had been delivered by Cesarean section in the 8th month of her mother’s pregnancy because of pre-eclampsia. Her mother suffered from MA and MO, but no other member of her family had a history of epilepsy. The patient was slightly mentally retarded, the cause of which had been investigated in her childhood. This investigation did not reveal any organic ﬁndings. The patient had frequented a professional school. She underwent menarche when she was 11 years old and her menstrual cycles were regular. When the patient was 5 years old, she developed epileptic seizures that were typical of absence and tonic-clonic seizures. She was treated initially with phenobarbital and ethosuximide and then later with valproic acid (VPA). From the age of 8 years, the antiepileptic therapy was effective, and provided complete control of the attacks and electroencephalogram (EEG) normalization. The patient discontinued her therapy when she was 20 years old. From 2000 onward, the patient began experiencing MO attacks, which were characterized by a pulsating pain and were accompanied by phonophobia, photophobia, nausea, and often vomiting. She reported having between 2 and 3 attacks each month. One of the attacks was related to hermenses. The duration was between 8 and 12 hours.
Conﬂict of Interest: None
The results of the EEG revealed slightly abnormal activity. Case Two. was started. with nausea. During 1 attack. At the time. At the time of the patient’s birth. coagulation studies.—A 31-year-old woman bookshop clerk was admitted to the emergency room (ER) with status epi- DISCUSSION The literature considered for the deﬁnition of “migralepsy. all of which were aggravated by physical movement. showed prolonged bursts of spikes in the right temporal region with hemispheric diffusions. basic metabolic and thyroid function tests. she had 3 tonic-clonic epileptic seizures with morsus and incontinence. the patient. she reported: “I see like a sparkling top. Over the next 3 years. an ECG.” This event. and laboratory investigations.Therapy with 400-mg carbamazepine b.d.i. When the patient was 3 years old. neurological. X-ray of the chest. The results of physical and neurological examinations. and the treatment provided her with complete control of the seizure and migraine attacks. we found . Her therapy was then modiﬁed. in the drowsiness phase. These seizures were left motor focal seizures and showed secondary generalization with tonicclonic seizures and the development of status epilepticus. His mother had suffered from MO but the patient reported that he had never suffered previously from migraine or had any seizures. All the seizures occurred while she was experiencing an MO attack.1130 The patient treated herself with a nonsteroidal antiinﬂammatory drug. she had 3 generalized tonic-clonic seizures within a few months. and extracranial and transcranial Doppler sonography were normal. Both attacks lasted about 5 hours and developed in the evening. which lasted about 30 minutes. Case Three.d. When she was 26. status epilepticus developed. and laboratory examinations. she had a generalized tonicclonic epileptic seizure. and photophobia. therapy with 300-mg VPA b. and the treatment was efﬁcacious. The patient was treated with intravenously administered lorazepam. which included a complete blood count.d. The results of the EEG.—A 19-year-old man student presented after 2 MO attacks. She was then transferred to the Neurologic Clinic for further assessment and subsequent treatment. July/August 2008 lepticus. she experienced an attack that was characterized by visual disturbance. The results of follow-up examinations and of the EEG that were performed during the subsequent 18 months were negative and the patient reported that he was no longer experiencing MO attacks and seizures.i. and at present the patient is being treated with 1800 mg/day VPA and 1000-mg levetiracetam b. and a single case report in which the seizure was preceded by an MO attack and was due to a reversible lesion.d. after being free of seizures for 23 years. the patient rested in bed and. was derived by reviewing 2 published reports of 13 and 7 cases of MA. he developed tonic-clonic seizures with tongue biting and incontinence. the patient vomited.6. During the attacks. The physical.5. In each attack.i. severe. during which a generalized epileptic attack with tonic-clonic seizures occurred.8 In the literature. VPA was substituted with 100-mg lamotrigine b. 2 months apart from one to the other. During her transfer to the hospital and again in the ER. he reported that he had had 2 migraine attacks. Treatment with lamotrigine controlled the epileptic attacks. and diffuse pain that was aggravated by physical movement and was accompanied by nausea and vomiting. and radiological examination of the chest were negative. electrocardiogram (ECG).” in the references reported in ICHD-II. was followed by pulsating. an ECG. which recurred at a frequency of 2 attacks each month. The results of an interictal EEG showed only rare bursts of bilateral temporal sharp activity. and brain magnetic resonance imaging (MRI) and angio-MRI using gadolinium. She was married and was the mother of a 6-yearold daughter.At the time of presentation. which was performed in the ER. as veriﬁed by a brain MRI scan. presented again with a tonic-clonic generalized epileptic attack and had a further 5 such attacks during the next 2 years. the patient has had 5 attacks of MA that were followed 2 or 3 hours later by an epileptic seizure. The results of the laboratory investigations. were negative. which was maintained until she was 10 years old. The results of the EEG performed some hours after the attacks showed only frontal minor sharp activity. but not the MO attacks. The results of brain MRI without enhancement by gadolinium showed numerous alterations in the region of the periventricular white matter. On one occasion. brain imaging (MRI and angio-MRI using gadolinium). at home. was started.This ﬁnding was considered to be due to the hypoxic event that occurred at the time of her birth. X-ray of the chest. After the second attack. which resolved the attack. he experienced pulsating pain in the left periorbital region. She has remained asymptomatic for the last 2 years for both attacks of MA and epileptic seizures. her mother had had a dystocic labor that required a forceps delivery that resulted in hypoxic congenital encephalopathy. without neurological deﬁcit. After about 3 hours. The patient recommenced antiepileptic therapy with VPA. turning increasingly faster to the left side. because of an increase in the activity of her serum transaminases.i. In 2003. phonophobia. which included a complete blood count. She started treatment with phenobarbital. After 8 months.
Cephalalgia. 1999. 1991. Headache Classiﬁcation Subcommittee of the International Headache Society. MA: Butterworth. in which imaging studies point to the presence of silent cortical spreading depression. 2004. we suggest that these deliberations consider also that migralepsy include MA-associated epileptic seizures that occur during a migraine attack.9 The ﬁrst of these reports was published before the publication of IHS classiﬁcation in 1988. Epilepsy and migraine. Furthermore. Dozing and sleep are conditions that can lower the seizure threshold. . Niedermeyer E.6 According to the deﬁnition given in ICHD-II. there are 2 published case reports of MA. Therefore. Lipton RB. in which a correlation between MA and epileptic seizures exists. but also MO) on a pre-existing low epileptic threshold. 7. 2003.40:487490.11. Ludvigsson et al reported that MA could be considered a risk factor for unprovoked seizures in children. both seizures occurred between 4 and 5 hours after the beginning of an MO attack.21-23 Moreover. Dodick DW.24 (Suppl. Velioglu SK. 1993. We highlight that this patient. Headache. which is a case of probable migraine because the patient had only 2 attacks.22.23 without an evident clinical correlate.20 In this report. Lugaresi E. Neurology.12 Therefore.19:797-801. Clin EEG. 6. with reference to the ﬁrst of these 2 issues. Migraine-related seizures in an epileptic population. 2.19 and 4 patients in a series of 59 patients with preictal headache in partial epilepsy.24:37-43. Clinical features of migraine-epilepsy syndrome. 7):S28-S32. we hypothesize that the organic birth-related brain damage could favor seizures.7-3%). The international classiﬁcation of headache disorders: 2nd edition. REFERENCES 1. 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