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© 2022 International League Against Epilepsy.Objective: The link between headache and epilepsy is more prominent in patients with idiopathic/genetic epilepsy (I/GE). We aimed to investigate the prevalence of headache and to cluster patients with regard to their headache and epilepsy features. Methods: Patients aged 6–40 years, with a definite diagnosis of I/GE, were consecutively enrolled. The patients were interviewed using standardized epilepsy and headache questionnaires, and their headache characteristics were investigated by experts in headache. Demographic and clinical variables were analyzed, and patients were clustered according to their epilepsy and headache characteristics using an unsupervised K-means algorithm. Results: Among 809 patients, 508 (62.8%) reported having any type of headache; 87.4% had interictal headache, and 41.2% had migraine. Cluster analysis revealed two distinct groups for both adults and children/adolescents. In adults, subjects having a family history of headache, ≥5 headache attacks, duration of headache ≥ 24 months, headaches lasting ≥1 h, and visual analog scale scores > 5 were grouped in one cluster, and subjects with juvenile myoclonic epilepsy (JME), myoclonic seizures, and generalized tonic–clonic seizures (GTCS) were clustered in this group (Cluster 1). Self-limited epilepsy with centrotemporal spikes and epilepsy with GTCS alone were clustered in Cluster 2 with the opposite characteristics. For children/adolescents, the same features as in adult Cluster 1 were clustered in a separate group, except for the presence of JME syndrome and GTCS alone as a seizure type. Focal seizures were clustered in another group with the opposite characteristics. In the entire group, the model revealed an additional cluster, including patients with the syndrome of GTCS alone (50.51%), with ≥5 attacks, headache lasting >4 h, and throbbing headache; 65.66% of patients had a family history of headache in this third cluster (n = 99). Significance: Patients with I/GE can be clustered into distinct groups according to headache features along with seizures. Our findings may help in management and planning for future studies.

Aim: Migralepsy is a clinical entity that occasionally represents a diagnostic problem. An apparent history and clinical manifestation of migraine may mask the epileptic attack accompanying migralepsy. The aim of this study is to present our experience with clinical and electroencephalography (EEG) findings and treatment of our patients diagnosed with childhood migralepsy disease.Methods: We documented six patients who were initially followed-up with a diagnosis of migraine, subsequently observed to have epileptic seizures, and then diagnosed with migralepsy.Result: Our patients became asymptomatic by giving good responses to antiepileptic therapy based on clinical and electroencephalography (EEG) findings.Conclusions: This case series shows that EEG recording can be useful in all stages of migraine for long-term, safe monitoring. Identifying patients with possible migralepsy will enable them to receive antiepileptic treatment.

Purpose To describe the concept, features and mechanisms of epileptic headache (EH). Methods Analysis of all published articles concerning EH and related subjects. Results There are more than 30 published case studies of patients with headache as the only manifestation of a seizure, a condition that has been variously called "EH", "ictal epileptic headache", "hemicrania epileptica", "cephalic pain seizure". It is necessary to differentiate EH from "migralepsy" and "ictal non-epileptic headache". EH may be an isolated event or the initial phase of a seizure followed by other manifestations. An isolated EH is clinically relevant because it is often symptomatic of structural brain disease; this underlines the importance of a differential diagnosis as the head pain of EH has no specific diagnostic characteristics. The described cases indicate that the location of the foci may vary, thus suggesting the involvement of different parts of the pain network. EH is a "focal aware" seizure, but there are a few reports of cases in which it was associated with generalised epileptiform activity. A correct diagnosis of EH requires an ictal EEG recording showing epilepsy-compatible discharges that coincide with the onset and cessation of the headache. A rapid response to the acute administration of an antiepileptic drug may support the diagnosis. Conclusions EH is a particular type of pain seizure that has a complex pathophysiology and, when isolated, requires differential diagnostic consideration. We believe that, although it is not frequent, pain as an ictal symptom should be highlighted in the operational classification of seizure types.

Introduction and objectives: Headaches (including migraines) and epilepsy have a high level of comorbidity and may be confused during diagnosis. Although physicians have known for centuries that these two conditions are somehow linked, their relationship remains poorly understood. Herein we describe the known associations between them, their underlying physiopathologic and genetic mechanisms, and the treatments recommended for them. Method: We have reviewed the most relevant publication of headache/migraine and epilepsy by using the PubMed data base. Description: An individual can suffer both from headaches (either migraine and/or other type of headache) and epilepsy, either by chance or because of a common underlying pathology. In these cases, the headache usually occurs at a different moment than the seizure (“interictal headache”). However, headaches sometimes occur simultaneously with, or very close in time to, the seizure: one that occurs at the same time as an epileptic seizure is known as an “ictal epileptic headache” or as “hemicrania epileptica”; one that precedes a seizure is known as a “pre-ictal headache”; and one that follows a seizure is known as a “post-ictal headache”. There is a particular type of pre-ictal headache, known as “migralepsy”, which occurs during or just after a migraine aura. Conclusions: The terminology and concepts employed to describe possible associations between headaches (mainly migraines) and epilepsy have evolved over time with increasing clinical and physiopathogenic knowledge. Some researchers have suggested eliminating the term migralepsy and using the terms ictal epileptic headache and hemicrania epileptica exclusively and uniformly in all classification systems. Resumen: Introducción y objetivos: Cefalea (especialmente la migraña) y epilepsia son entidades con elevada comorbilidad que pueden confundirse desde el punto de vista clínico. Existe una relación bidireccional entre ambas, conocida desde hace siglos, pero aún no bien comprendida. Describimos las distintas modalidades de asociación existentes entre ellas, los mecanismos fisiopatológicos y genéticos subyacentes y los tratamientos recomendados. Método: Hemos revisado las publicaciones más relevantes sobre la asociación entre migraña/cefalea y epilepsia utilizando la base de datos de PubMed. Descripción: En un mismo individuo, la epilepsia puede coexistir con algún tipo de cefalea (sobre todo migraña) por azar o a través de una etiología subyacente común. En ambos casos, los ataques de una y otra se presentan en diferentes momentos temporales (“cefalea interictal”). Cuando la cefalea es parte de la propia crisis, estamos ante una hemicránea epiléptica o ante una cefalea epiléptica ictal. La cefalea que aparece tras la crisis, define una cefalea post-ictal. La cefalea que la precede, se denomina cefalea preictal. Un tipo especial de esta última es la migralepsia, término que hace referencia a las crisis que aparecen durante o poco después del aura migrañosa. Conclusiones: La terminología y los conceptos que definen las posibles asociaciones entre cefalea/migraña y epilepsia han ido evolucionando a lo largo del tiempo, en virtud del mayor conocimiento clínico y fisiopatogénico. Se ha propuesto suprimir el término de migralepsia, y utilizar de forma restringida y uniforme los términos cefalea epiléptica ictal y hemicránea epiléptica en todos los sistemas de clasificación. Keywords: Aura, Headache, Epileptic seizures, Epilepsy, Migralepsy, Migraine, Palabras clave: Aura, Cefalea, Crisis epiléptica, Epilepsia, Migralepsia, Migraña

Purpose There are different possible temporal associations between epileptic seizures and headache attacks which have given rise to unclear or controversial terminologies. The classification of the International League Against Epilepsy does not refer to this type of disorder, while the International Classification of Headache Disorders (ICHD-2) defines three kinds of association: 1. migraine-triggered seizure ("migralepsy"), 2. hemicrania epileptica, and 3. post-ictal headache. Methods We performed an extensive review of the literature, not including "post-ictal" and "inter-ictal" headaches. Results On the basis of well-documented reports, the following clinical entities may be identified: (A) "epileptic headache (EH)" or "ictal epileptic headache (IEH)": in this condition headache (with or without migrainous features) is an epileptic manifestation per se , with onset, and cessation if isolated, coinciding with the scalp or deep EEG pattern of an epileptic seizure. EH maybe followed by other epileptic manifestations (motor/sensory/autonomic); this condition should be differentiated from "pure" or "isolated" EH, in which headache/migraine is the sole epileptic manifestation (requiring differential diagnosis from other headache forms). "Hemicrania epileptica" (if confirmed) is a very rare variant of EH, characterized by ipsilateral location of headache and ictal EEG paroxysms. (B) "Pre-ictal migraine" and "pre-ictal headache": when a headache attack is followed during, or shortly after, by a typical epileptic seizure. The migraine attack may be with or without aura, and its seizure-triggering role ("migraine-triggered seizure") is still a subject of debate. A differentiation from occipital epilepsy is mandatory. The term "migralepsy" has not been used uniformly, and may therefore led to misinterpretation. Conclusions On the basis of this review we suggest definitions and a terminology which may become the basis of a forthcoming classification of headaches associated with epileptic seizures.

The connection between the episodic conditions, migraine and epilepsy, is widely acknowledged but the mechanism involved is subject to debates. Similarly, the role of maintenance opioid in preventing migraine and related entities is well known but few reports exist on the prophylactic use of opioids in preventing both migraine and epilepsy (migralepsy) proven refractory to the use of conventional anticonvulsants. Here, I provide details of a patient with refractory migralepsy who responded favourably to daily scheduled opioid, with eventual complete remission of headaches and seizures at a high dose of oxycodone.

The term "ictal epileptic headache" has been recently proposed to classify the clinical picture in which headache is the isolated ictal symptom of a seizure. There is emerging evidence from both basic and clinical neurosciences that cortical spreading depression and an epileptic focus may facilitate each other, although with a different degree of efficiency. This review address the long history which lead to the 'migralepsy' concept to the new emerging pathophysiological aspects, and clinical and electroencephalography evidences of ictal epileptic headache. Here, we review and discuss the common physiopathology mechanisms and the historical aspects underlying the link between headache and epilepsy. Either experimental or clinical measures are required to better understand this latter relationship: the development of animal models, molecular studies defining more precise genotype/phenotype correlations as well as multicenter clinical studies with revision of clinical criteria for headache-/epilepsy-related disorders represent the start of future research. Therefore, the definition of ictal epileptic headache should be used to classify the rare events in which headache is the only manifestation of a seizure. Finally, using our recently published criteria, we will be able to clarify if ictal epileptic headache represents an underestimated phenomenon or not.

The International League Against Epilepsy (ILAE) Commission on Classification and Terminology has revised concepts, terminology, and approaches for classifying seizures and forms of epilepsy. Generalized and focal are redefined for seizures as occurring in and rapidly engaging bilaterally distributed networks (generalized) and within networks limited to one hemisphere and either discretely localized or more widely distributed (focal). Classification of generalized seizures is simplified. No natural classification for focal seizures exists; focal seizures should be described according to their manifestations (e. g., dyscognitive, focal motor). The concepts of generalized and focal do not apply to electroclinical syndromes. Genetic, structural-metabolic, and unknown represent modified concepts to replace idiopathic, symptomatic, and cryptogenic. Not all epilepsies are recognized as electroclinical syndromes. Organization of forms of epilepsy is first by specificity: electroclinical syndromes, nonsyndromic epilepsies with structural-metabolic causes, and epilepsies of unknown cause. Further organization within these divisions can be accomplished in a flexible manner depending on purpose. Natural classes (e. g., specific underlying cause, age at onset, associated seizure type), or pragmatic groupings (e. g., epileptic encephalopathies, self-limited electroclinical syndromes) may serve as the basis for organizing knowledge about recognized forms of epilepsy and facilitate identification of new forms.

Purpose and methods Migraine, with or without aura, affects from 10% to 14% of the population, and is as such one of the most common headache disorders. A unified hypothesis for the physiopathology of migraine and its relationship with epileptic migraine and migralepsy has yet to be formulated. Trigemino-vascular system (TVS) activation is believed to play a crucial role in the "pain phase" in migraine; cortical spreading depression (CSD) is considered to be the primary cause of TVS activation. On the basis of data in the literature, I would like to stress that TVS activation may originate at different cortical and subcortical levels. For example, as recently reported, an epileptic focus, originating and propagating along cortical non-eloquent/silent areas, through CSD, rarely causes TVS activation with migraine as the sole ictal epileptic manifestation. Results and conclusion The multiple considerations that arise from this hypothesis, including the under-diagnosed ictal epileptic headache, are discussed; EEG (ictal and inter-ictal) recording with intermittent photic stimulation (IPS), according to the standardized international protocol, is strongly recommended in selected migraine populations.

Background Headache and epilepsy are two paroxysmal disorders with epidemiological and clinical comorbidity. Among the primary headaches, migraine, and in particular the subtype with aura (MA) has a significant correlation with epilepsy. Like epilepsy MA is a chronic condition characterized by recurrent focal neurological attacks that are variously accompanied by headache and inconstant autonomic features. Interictal electroencephalogram (EEG) findings are usually normal although several abnormalities, especially diffuse slowings, have been reported in migraineurs. EEG is not useful in MA with the exception of situations where seizure disorders are to be excluded. The relationship between headaches and epilepsy is covered in the International Classification of Headache Disorders in chapters 1 and 7 where migraine-triggered seizure (1.4.4), hemicrania epileptica (7.6.1) and post-ictal headache (7.6.2) are collocated. An interictal headache was defined as headache starting not earlier than three hours after a seizure or a headache never proceeding directly into an epileptic fit. Headache caused by an epileptic seizure, occurring during and/or after the seizure and remitting spontaneously within hours or up to 3 days [1,2]. The classification of the International League against Epilepsy does not refer to this type of disorder. In the last decade other terms for this association have been proposed (epileptic headache or ictal epileptic headache) and some Authors have proposed to abandon or modify some terms (hemicrania epileptica and migralepsy) [3-5].

Migraine and epilepsy are common neurological conditions that may share a pathophysiologic and genetic basis. The following case is presented to illustrate key aspects of their relationship.

Migraine and epilepsy are both common episodic disorders that share many clinical features and underlying pathophysiological mechanisms. The comorbidity of these two conditions is well known. However, the temporal association between migraine and epilepsy is a controversial issue, since these two conditions may occur in numerous ways. Four types of association between headache and epileptic seizure are recognized: pre-ictal headache, headache as the expression of an epileptic manifestation, post-ictal headache, and inter-ictal headache. The classification of epilepsy by the International League Against Epilepsy did not refer to the epileptic headache. On the other hand, the International Classification of Headache Disorders, 3rd edition (ICHD-3) defines three entities: migraine aura-triggered seizure which sometimes referred to as migralepsy, hemicrania epileptica, and post-ictal headache. However, ICHD-3 mentions that there is a complex and bidirectional association between migraine and epilepsy. Most of the previous reports of migralepsy corresponded to occipital seizures that mimic migraine with aura. The term migralepsy has recently been criticized. Migraine and epilepsy share several pathophysiological mechanisms which involve neurotransmitters and iron channel dysfunctions. There is the hypothesis of a shared genetic susceptibility to migraine and epilepsy. Strong support of a shared genetic basis comes from familial hemiplegic migraine.

Summary: Purpose: Headache is often ignored as a symptom of epileptic seizures. The purpose of this prospective study was to analyze frequency, classification, and characteristics of seizure-associated headache (SH) according to the criteria of the International Headache Society. Methods: Over a period of 15 months, 341 patients with epilepsy, consecutively evaluated at our outpatient clinic for SH, completed a standardized questionnaire. Results: Of the 341 epilepsy patients, 115 (34%) experienced SH with a pain intensity of 6.1 ± 1.6 (SD) on the visual analogue scale and a duration of 12.8 ± 15.7 (SD) h. Seizures were always accompanied by headache in 69 (60%) of these 115 patients. SH occurred in four (3%) of 115 patients only preictally, in 31 (27%) of 115 patients periictally, and in 80 (70%) of 115 patients only postictally. In the majority of the 115 patients (55.7%), SH could be classified as migraine headache, whereas in 36.5%, as tension-type headache. The type of SH was not correlated with sex, an epilepsy syndrome, or a seizure type. Migraine-like SH was significantly associated with a history of migraine (p < 0.001). In 20 (77%) of the 26 patients experiencing migraine-like SH with a history of migraine, the phenomenology of migraine-like SH and migraine attacks was identical. Conclusions: SH is a frequent, long-lasting, and severe symptom of epileptic seizures, causing major impairment of daily living. A history of migraine significantly increases the risk for developing migraine-like SH.

A relationship between epilepsy and migraine has long been postulated, but the nature of this interaction is still debated. We studied adult patients with epilepsy and investigated the relationship between migraine and epilepsy. Fourteen percent ( n=412) of adult patients with seizures were identified with a diagnosis of migraine. We also found a direct relationship between migraine and epilepsy (a migraine-induced epilepsy) in 1.7% (seven patients) of the patients with seizures. Patients were at increased risk for both conditions if they had migraine with aura and catamenial epilepsy. The seizure began during or shortly after the migraine aura in all of the cases and preceded the headache. Three of four patients who were refractory to management with antiepileptic drugs using either mono or combination therapy improved seizure control with combination antimigraine and antiepileptic drugs.

This is a qualitative and chronological analysis of ictal and postictal symptoms, frequency of seizures, family history, response to treatment, and prognosis in nine patients with idiopathic occipital epilepsy and visual seizures. Ictal elementary visual hallucinations are stereotyped for each patient, usually lasting for seconds. They consist of mainly multiple, bright coloured, small circular spots, circles, or balls. Mostly, they appear in a temporal hemifield often moving contralaterally or in the centre where they may be flashing. They may multiply and increase in size in the course of the seizure and may progress to other non-visual occipital seizure symptoms and more rarely to extra-occipital manifestations and convulsions. Blindness occurs usually from the beginning and postictal headache, often indistinguishable from migraine, is common. It is concluded that elementary visual hallucinations in occipital seizures are entirely different from visual aura of migraine when individual elements of colour, shape, size, location, movement, speed of development, duration, and progress are synthesised together. Postictal headache does not show preference for those with a family history of migraine. Most of the patients are misdiagnosed as having migraine with aura, basilar migraine, acephalgic migraine, or migralepsy simply because physicians are not properly informed of differential diagnostic criteria. As a result, treatment may be delayed for years. Response to carbamazepine is excellent and seizures may remit.

Kelley et al. confirmed the higher prevalence of migraine in children with epilepsy.1 The authors expanded upon our hypothesis2 by assuming that migraine would be more prevalent in patients with intractable epilepsy. In our opinion, this was not shown. In patients with intractable seizures, the focus is primarily on seizures vs headache complaints. Children with benign epilepsy with centrotemporal spikes and juvenile myoclonic epilepsy are most prevalent in this study and because these types of epilepsy are relatively benign, these patients are more likely to complain of headache. Considering that headache occurs after epilepsy onset and often in the same year confirms our hypothesis.2

Basic and clinical neuroscience research findings suggest that cortical spreading depression (CSD) and epileptic foci may facilitate each other; furthermore, the threshold required for the onset of CSD has been suggested to be lower than that required for an epileptic focus. These data may explain the prevalence of epilepsy in migraine populations (ranging from 1% to 17%) and the frequency of migraine in epileptic populations (ranging from 8.4% to 20%). There is currently a considerable amount of confusion regarding this topic in both headache and epilepsy classifications (ICHD-II and ILAE). The ICHD-II includes “migraine-triggered seizure” (coded as “1.5.5”) (so-called “migralepsy”) among the “complications of migraine”, and defines “hemicrania epileptica” (“7.6.1”) as an “ictal headache” (ipsilateral to the ictal EEG discharge) that occurs “synchronously” with a seizure (partial epileptic seizure) recognized by ILAE classification. However, neither “migralepsy” nor “hemicrania epileptica” are terms used in the current ILAE classification. On the basis of data reported in the literature and our recent findings, we suggest that the terms “migraine-triggered seizure” and “migralepsy” be deleted until unequivocal evidence of the existence of these conditions emerges. “Ictal epileptic headache” (IEH) should be used to classify those rare events in which headache represents the sole ictal epileptic manifestation. On the other hand, the term “hemicrania epileptica” should be maintained in the ICHD-II and introduced into the ILAE, and be used to classify all cases in which an “ictal epileptic headache” “coexists” and is associated synchronously or sequentially with other ictal sensory-motor events.

Despite the fact that migraine and epilepsy are among the commoner brain diseases and that comorbidity of these conditions is well known, only few reports of migralepsy and hemicrania epileptica (HE) have been published according to the current ICHD-II criteria. Particularly, ICHD-II describes “migraine-triggered seizure” (i.e., migralepsy) among complications of migraine at “1.5.5” (as a rare event in which a seizure happens during migrainous aura), while hemicrania epileptica (coded at “7.6.1”) and post-ictal headache (coded at “7.6.2”) are described among headaches attributed to epileptic seizure. However, to date neither the International Headache Society nor the International League against Epilepsy mention that headache/migraine may be the sole ictal epileptic manifestation. Based on the current knowledge, migralepsy is highly unlikely to exist as such. We, therefore, propose to delete this term until clear evidence its existence is provided. Moreover, we herein propose a revision of terminology and classification criteria to properly represent the migraine/headache relationships. We suggest the term “ictal epileptic headache” in cases in which headache/migraine is the sole ictal epileptic manifestation.

Although headache and epilepsy have often been associated, the precise electroclinical and pathophysiological interaction between these disorders and in particular its relations with photosensitivity is as yet to be fully understood in adults or children. The association between headache and epilepsy commonly occurs in all types of epilepsy and not only in occipital epilepsy. Generally, peri-ictal headache is often neglected, regardless of its severity, because patients are more concerned about their seizures. Altered cerebral cortex excitability may be the link between these two conditions and photosensitivity shows this. The physician should bear this association in mind when dealing with epileptic and migraine patients so as to be able to offer such patients an accurate diagnosis and appropriate treatment; this should be borne in mind when declaring epileptic patients ‘seizure free’. To date neither the International Headache Society nor the International League against Epilepsy mention that headache/migraine may, on occasion, be the sole ictal epileptic manifestation. Lastly, studies designed to investigate the triggering role of photosensitivity in both headache and epilepsy are warranted.

Migralepsy is an ill-defined nosologic entity, with only a few cases described in the literature. In the 2004 International Classification for Headache Disorders (ICHD-II), the International Headache Society proposed that the following diagnostic criteria should be met: (1) migraine fulfilling criteria for 1.2 Migraine with aura (MA) and (2) a seizure fulfilling diagnostic criteria for one type of epileptic attack occurs during or within 1 h after a migraine aura. Herein, by presenting a case with symptoms suggestive of migralepsy and by reviewing all previous cases described in the literature, we discuss the challenges of differentiating this condition from epileptic seizures, as well as the inaccuracy of the current ICHD-II definition.

We report the history of a 14-year-old girl with atypical childhood occipital epilepsy "Gastaut type" whose first generalized tonic-clonic seizure was preceded by migraine without aura and followed by a status migrainosus. This status lasted for 3 days despite standard analgesic therapy. An EEG recording revealed an occipital status epilepticus during her migraine complaints. Seven minutes after intravenous administration of 10 mg diazepam under continuous EEG recording, a suppression of the epileptiform discharges over the right occipital was seen, while the headache subsided 3 min later. After precise questioning about the circumstances that possibly could have led to these events, it appeared that she had played for hours with a play station on the new color TV and she had visited an exhibition of Matisse and Bonnard with bright colors and contrast-rich text. Standardized extensive intermittent photic stimulation (IPS), 2 days after the status migrainosus, evoked besides asymmetrical right-sided driving, green spots in her left visual field, while in the EEG sharp waves were recorded over the right parietotemporal region. After further IPS with 20 Hz (eye closure), she started complaining of a light pulsating headache right occipitally and in the EEG right parietotemporal sharp-waves were seen. This lasted for about 10 min. Later, an interictal routine EEG was normal except for some theta over the right temporooccipital area. The most likely diagnosis is an atypical form of occipital epilepsy "Gastaut type." We would therefore advocate recording EEGs with photic stimulation in patients with atypical migraneous features.

To determine the lateralizing value of peri-ictal headache, the authors conducted a standardized interview of 100 patients with partial epilepsy, 60 with temporal lobe epilepsy (TLE) and 40 with extratemporal epilepsy (ETE). Peri-ictal headache occurred in 47 of 100 (47%) patients. Peri-ictal headache was more likely to be ipsilateral to the seizure onset in TLE (27 of 30 = 90%) than in ETE (two of 17 = 12%; p< 0.001). For both groups, peri-ictal headache usually conformed to the diagnostic criteria for common migraine (18 of 30 = 60% in TLE; 7 of 17 = 41% in ETE).

tory of epilepsy and migraine (Walker et al., 1995; Parisi et al., 2007; Piccioli et al., 2009). Reconsideration of the usefulness of EEG recording with IPS is thus necessary in those patients (Parisi et al., 2008a). In conclusion, although we agree with Sances et al. (2009), we do think that this ‘‘hot topic’’ should not be restricted to simply the redefinition of ‘‘migralepsy concept.’’ That would be a narrow point of view. We would like to stress the need for a revision of classification criteria that represent properly the migraine/headache, migralepsy, and epilepsy relationships. We propose the term ‘‘ictal epileptic headache’’ (Piccioli et al., 2009) as a new epileptic subtype within a new category called ‘‘autonomic epilepsy’’ (Parisi, 2009a,b), as previously (Ferrie et al., 2007) and more recently (Michael et al., 2009) suggested for PS.

The complex relationship between migraine and epilepsy is highlighted by the occurrence of a seizure during a migraine attack without aura. This phenomenon, referred to as migralepsy, suggests an inherent overlap in the underlying pathophysiology of these events. We report the case of a patient who had a generalized seizure, persistent nondominant hemisphere syndrome, and reversible magnetic resonance imaging abnormalities during a prolonged migraine attack without aura.

We tested the hypothesis that the comorbidity of migraine and epilepsy results from a shared genetic susceptibility to the two disorders. We used semistructured telephone interviews to collect information on migraine and epilepsy in the families (parents, siblings, and offspring) of 1,967 adult probands with epilepsy. Epilepsy was defined as a lifetime history of two or more unprovoked seizures, and migraine as self-reported severe headaches with two or more of the following symptoms: unilateral pain, throbbing pain, visual aura, or nausea. As a first test of the hypothesis of shared susceptibility, we assessed risk of migraine in relatives of probands with genetic versus nongenetic forms of epilepsy, using two proxy measures of genetic susceptibility-a first-degree family history of epilepsy and idiopathic/cryptogenic (versus postnatal symptomatic) etiology. Neither of these two measures was associated with risk of migraine in relatives. As a second test, we assessed risk of epilepsy in the relatives of probands with versus without migraine. With the exception of one subgroup (sons of female probands), risk of epilepsy in relatives was not associated with the proband's history of migraine. This pattern of results is inconsistent with the hypothesis of a shared genetic susceptibility to migraine and epilepsy.

An 31-year-old man had a unique form of occipital lobe epilepsy. Since age 13 years, he has had episodes of simple partial status epilepticus (SE) occurring twice a month. These typically consisted of elementary visual hallucinations of flashing lights obscuring his left visual field for a period of 2 days, associated with a severe frontal headache initially diagnosed as migraine. These episodes of simple partial SE then evolved to a complex partial seizure (CPS) or secondarily generalized seizure. There were unique EEG features, including: (a) the perception of a flash of light in the left visual field with a single sharp/slow wave discharge over the right occipital lobe, (b) right occipital lobe epileptiform activity during the prolonged aura, and (c) an abnormal response to photic stimulation, with occipital lobe discharges during low rates of stimulation (3-5 Hz), time-locked to the stimulus. High-resolution magnetic resonance imaging (MRI) with quantitative morphometry demonstrated that the right hemisphere and right caudate nucleus were smaller than those on the left. An abnormal gyral pattern was also noted over the right parietal region. Occasionally, distinguishing occipital lobe epilepsy from migraine may be difficult.

Dear Sir, We thank Dr. Striano and co-workers for their interest in our two recently published papers on comorbidity between headaches, in particular migraine, and epilepsy [1–3]. Dr. Striano underlies the importance of neuronal hyperexcitability and increased susceptibility to cortical spreading depression, sustained by both genetic and non-genetic factors, as the main pathophysiological mechanism of this association, accordingly to other authors [2–4]. Dr. Striano correctly points out that large well-phenotyped samples and massive genotyping will give a chance to discover the genetic factors involved in the comorbidity between headache/migraine and epilepsy [1]. The two main aspects that complicate the analysis of the molecular mechanisms underlying the comorbidity between headache/migraine and epilepsy are: (1) that while some epileptic syndromes are monogenic, apart from the exception of hemiplegic migraine, common forms of migraine are multifactorial and polygenic diseases; (2) the neuronal depolarization that gives rise to a seizure and the cortical spreading depression that causes migraine share some pathophysiological mechanisms. We believe that some clinical markers (such as the presence of EEG photosensitivity, osmophobia, family history of epilepsy and headache, migraine aura) could help to select more homogeneous populations of patients for genotype analysis, therefore it is important to collect cases, prospectively, with extensive phenotypic characterization. For this purpose well-designed multicenter studies are desirable to achieve a high sample size. Another important point raised by Dr. Striano is the need to revise the international classification of both epilepsy and headache disorders and to introduce widely accepted and more precise diagnostic criteria of migralepsy, hemicrania epileptica, post-ictal headache and “ictal epileptic headache” [1, 5, 6]. Further studies are necessary to clarify the pathopshysiological mechanisms of the association between headache/migraine and epilepsy.