The complex interrelations between two paroxysmal disorders: headache and epilepsy

The interrelations between headache/migraine and epileptic seizures are an interesting topic, still lacking a systematization, which is the objective of the present revision. We organize the general setting on: (a) a distinction between pre-ictal, ictal, post-ictal and inter-ictal headaches, assuming “ictal” as epileptic seizure, and (b) the kind of headache, if it is of migraine type or not. Concerning pre-ictal migraine/headache, the necessity of its differentiation from an epileptic headache presenting as an aura of a seizure is stressed; this is connected with the indefiniteness of the term “migralepsy”. The term “migraine aura-triggered seizure” should be used only in front of a proven triggering effect of migraine. Epileptic headache (called also “ictal epileptic headache”) is a well-characterized entity, in which different types of head pain may occur and an ictal EEG is necessary for the diagnosis. It may present as an isolated event (“isolated epileptic headache”), requiring a differential diagnosis from other kinds of headache, or it may be uninterruptedly followed by other epileptic manifestations being in this case easily identifiable as an epileptic aura. Hemicrania epileptica is a very rare variant of epileptic headache, characterized by the ipsilaterality of head pain and EEG paroxysms. Ictal non-epileptic headache needs to be differentiated from epileptic headache. Post-ictal headaches are a frequent association of headache with seizures, particularly in patients suffering also from inter-ictal headache-migraine. The reported systematization of the topic led us to suggest a classification which is shown in Appendix.     

Should "migralepsy" be considered an obsolete concept? A multicenter retrospective clinical/EEG study and review of the literature

The few reports that have been published on the current International Classification of Headache Disorders, Second Edition (ICHD-II), criteria for migralepsy and hemicrania epileptica have highlighted the considerable confusion regarding this "hot topic" within both headache and epilepsy classifications (ICHD-II and International League Against Epilepsy [ILAE]). Indeed, the ICHD-II describes a migraine-triggered seizure as a rare event in which a seizure occurs during migraine aura; on the other hand, hemicrania epileptica is described as an "ictal headache" that occurs "synchronously" with a partial seizure. To confuse matters even further, neither the term migralepsy nor the term hemicrania epileptica is included in the currently used ILAE classification. On the basis of both a review of "migralepsy" cases in the literature and 16 additional retrospective multicenter cases, we suggest that the term migraine-triggered seizure or migralepsy be deleted from the ICHD-II classification until unequivocal evidence is provided of its existence, and that the term ictal epileptic headache be introduced into the ILAE classification.     

Why is migraine rarely,and not usually,the sole ictal epileptic manifestation?

Purpose and methodsMigraine, 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 conclusionThe 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.     

Epileptic seizure and migraine visual aura: revisiting migralepsy

INTRODUCTION: The term of "migralepsy" has been proposed to define migraine-triggered epileptic seizures. Although already reported in the literature for more than fifty years, a number of observations remain debatable because of possible confusion between migraine and epileptic seizure clinical manifestations, including hemifield visual hallucinations, digestive signs and severe headache. OBSERVATION: We report on the case of a young patient suffering from both diseases, in whom a visual aura preceded either migraine attacks or epileptic generalized tonic-clonic seizure. Subtle modification in the primitive visual hallucination, which suddenly contained colored figures and was accompanied by fear before a prolonged loss of contact, suggested a continuum between migraine aura and epileptic seizure in this patient. Brain MRI was normal and EEG showed some sharp waves in the right posterior area. CONCLUSION: The presence of a neurophysiological continuum between migrainous aura and epileptic seizure is supported by this observation of "migralepsy". Recent findings from genetic and epidemiological studies further support this link.     

Ictal epileptic headache in adult life: Electroclinical patterns and spectrum of related syndromes

ObjectivesBoth headache and epilepsy are frequent paroxysmal disorders that often co-occur or are related in numerous ways. Although ictal epileptic headache has become the focus of several studies, this remains a very rare and not well-known phenomenon. Electroclinical features, pathophysiology, and syndromic context are heterogeneous. We investigated the electroclinical and neuroimaging findings in a population of adult patients with ictal epileptic headache.MethodsWe retrospectively examined 8800 EEG recordings of almost 4800 patients admitted to our video-EEG laboratory from 2010 to 2013 with a history of well-documented epilepsy. We selected patients who reported headache closely related to a seizure documented by video-EEG or 24-hour ambulatory EEG. We analyzed ictal electroclinical features of headache, and we defined the related epileptic syndromes.ResultsWe identified five patients with ictal epileptic headache. Two patients described tension headache during an epileptic seizure. In three patients, the headache was accompanied by other “minor” neurological symptoms mimicking a migrainous aura. In all cases, the headache stopped with the end of the epileptic activity. Three patients had a history of partial symptomatic epilepsy with cerebral lesions (low grade glioma, astrocytoma, porencephalic cyst) in the left posterior regions, whereas two patients were affected by idiopathic generalized epilepsy.ConclusionThis study confirms the rarity of ictal epileptic headache. To date, well-documented video-EEG cases remain as exceptional reports, especially in cases of idiopathic generalized epilepsies. Moreover, we confirm the main involvement of posterior regions in patients with ictal epileptic headache affected by partial symptomatic epilepsies.     

What have we learned about ictal epileptic headache? A review of well-documented cases

PurposeThe case report published in this issue by Wang et al. offers us an opportunity to review previously published “ictal epileptic headache” cases and draw attention to the criteria that have recently been published for this condition, taking into consideration not only the clinical-EEG and physiopathogenetic investigations required to diagnose this condition, but also the therapeutic aspects of the issue.MethodsTo this aim we reviewed all well-documented cases that have been reported in the literature.ResultsThe relationship between headache and seizures is somewhat complicated. Although the nature of this association is not yet fully clear, several plausible explanations have been proposed. Further experimental and clinical investigations are, however, warranted to gain a better understanding of this relationship. Epilepsy and idiopathic headache/migraine share several pathophysiological mechanisms; a better understanding of these mechanisms will allow us to more accurately to assess the “real burden” and prevalence of the “ictal epileptic headache” phenomenon and its therapeutic implications.ConclusionsThe development of animal models and molecular studies and, above all, multicenter clinical studies conducted according to the proposed IEH criteria represent the starting point for a definitive international consensus on this intriguing topic. In addition, to improve the recognition of ictal epileptic headache, we should encourage the use of EEG recording in the emergency setting.     

Migralepsy: A Borderland of Wavy Lines

The special relationship between migraine and epilepsy has been recognized for centuries and was formally acknowledged by Gowers in his 1906 lecture “Borderland of Epilepsy.” The term migralepsy was introduced by Lennox and Lennox in 1960, with multiple cases described in the literature since that time. In the ensuing years, the relationship between migraine and epilepsy has proven complex. The 2 conditions have been found to be comorbid with each other, suggesting a common underlying mechanism or genetic tendency. Specific diseases with both phenotypes provide further evidence of a common pathophysiology, and as the mechanism of migraine has been further elucidated, commonalities with seizure have been recognized. The terms “hemicrania epileptica” and “migraine triggered seizure” were defined by the International Headache Society, formalizing the concept that one can lead to the other. However, case reports and case series in the literature reveal that distinguishing between the 2 entities can be challenging. The concept of migralepsy is likely to evolve as greater understanding of both conditions is gained.     

Relations between epileptic seizures and headaches

PurposeTo describe headaches in patients with epilepsy and try to identify relations between epileptic seizures and headaches.MethodsCross-sectional study, with 304 patients from the epilepsy out-patient section of University Hospital of Federal University of Alagoas (Brazil) between February 2007 and February 2008. The presence of headaches and their relationships with the epileptic seizures were analyzed.ResultsFrequent seizures were associated with a greater tendency of occurrence of headaches (odds ratio = 1.6 times, p = 0.077). Headaches occurred in 66.1% of the cases. The highest occurrence was of migraine (32.9% of the patients), followed by tension-type headaches (9.2%). Two syndromes with a continuum epilepsy–migraine in the same seizure are worth mentioning: migralepsy in 6.6% and epilepgraine in 10.2% of the patients with epilepsy.ConclusionsA high prevalence of headaches in patients with epilepsy was observed, with emphasis on hybrid crises of epilepsy and migraine.     

From migralepsy to ictal epileptic headache: the story so far

In the last few years several cases of headache as sole manifestation of an epileptic seizure have been reported and the term “ictal epileptic headache” has been recently proposed to identify an EEG-recorded epileptic seizure with migraine/headache-like features. Among the potential practical implications arising from these clinical observations, there is the urgent need for a revision of both International Classifications of Epilepsy and Headache disorders. We discuss these topics and provide additional comments about the physiopathological links between epilepsy and migraine.     

Spiritual/religious coping in patients with epilepsy: Relationship with sociodemographic and clinical aspects and quality of life

The relationship between headache and seizures is a complicated one, since these two conditions are related in numerous ways.Although the nature of this association is unclear, several plausible explanations exist: the two disorders coexist by chance; headache is part (or even the sole ictal phenomenon) of seizures or the post-ictal state; both disorders share a common underlying etiology; and epilepsy mimics the symptoms of migraine (as in benign childhood epilepsy).Seizures and headaches as well as their respective primary syndromes (epilepsy and headache/migraine) share several pathophysiological mechanisms. These mechanisms especially involve neurotransmitter and ion channel dysfunctions. Also, photosensitivity seems to play a role in the connection. In order to improve the care for patients with a clinical connection between migraine and epilepsy, it is necessary to try to understand more accurately the exact pathophysiological point of connection between these two conditions. Both experimental and clinical measures are required to better understand this relationship. The development of animal models, molecular studies defining more precise genotype/phenotype correlations, and multicenter clinical studies with revision of clinical criteria for headache/epilepsy-related disorders represent the start for planning future translational research.In this paper, we review the relationship between migraine and epilepsy in terms of epidemiology and pathophysiology with regard to translational research and clinical correlations and classification.This article is part of a Special Issue entitled “The Future of Translational Epilepsy Research”.     

Ictal video-polysomnography and EEG spectral analysis in a child with severe Panayiotopoulos syndrome.

OBJECTIVE: To describe the ictal polysomnographic features of a patient with Panayiotopoulos syndrome, a peculiar epileptic syndrome characterized by infrequent, often single, prolonged, nocturnal, focal seizures comprising an unusual constellation of autonomic symptoms (malaise, nausea, pallor, tachycardia, vomiting) and unilateral deviation of the eyes at the onset of seizures. These clinical, ictal manifestations are rarely followed by post-ictal headache. In the literature, there is little information on the ictal EEG characteristics of Panayiotopoulos syndrome and, in particular, on certain autonomic manifestations, such as tachycardia, as the sole ictal phenomena at the onset of seizures. METHODS AND RESULTS: One, all-night videopolysomnography, during which one seizure was recorded. Video-EEG data were evaluated visually and by means of quantitative spectral analysis. The spectral analysis of the recorded seizure showed a complex ictal pattern of cortical involvement with focal onset in the right occipital area followed by the recruitment of widespread extra-occipital cortical regions. CONCLUSIONS: This is the first such analysis of this peculiar epileptic condition. Most of the symptoms were consistent with a diagnosis of severe Panayiotopoulos syndrome, although the patient also presented "atypical findings": a relatively high frequency of seizures, post-ictal headache, no spontaneous remission of seizures with age, and late onset of visual hallucinations; this last finding is more frequent in "Gastaut-type childhood occipital epilepsy", in which onset typically occurs later than in Panayiotopoulos syndrome. [Published with video sequences].     

Ictal headache: headache as first ictal symptom in focal epilepsy

Headache may be associated with seizures as a preictal, ictal, or postictal phenomenon, but it is often neglected because of the dramatic neurological manifestations of the seizure. Headache can also be the sole or predominant clinical manifestation of epileptic seizures, although this is a relatively rare condition. We describe two cases of focal symptomatic drug-resistant epilepsy with headache as the first ictal symptom. In both cases, the headache, which lasted a few seconds, was contralateral to the ictal discharge and did not have the clinical features of migraine. Ictal headache is a rare epilepsy symptom that can help to localize ictal EEG discharges. Recently, the term ictal epileptic headache has been proposed in cases in which headache is the sole ictal epileptic manifestation Diagnosis requires the simultaneous onset of headache with EEG-demonstrated ictal discharges.     

Ictal headache: Headache as first ictal symptom in focal epilepsy

Headache may be associated with seizures as a preictal, ictal, or postictal phenomenon, but it is often neglected because of the dramatic neurological manifestations of the seizure. Headache can also be the sole or predominant clinical manifestation of epileptic seizures, although this is a relatively rare condition. We describe two cases of focal symptomatic drug-resistant epilepsy with headache as the first ictal symptom. In both cases, the headache, which lasted a few seconds, was contralateral to the ictal discharge and did not have the clinical features of migraine. Ictal headache is a rare epilepsy symptom that can help to localize ictal EEG discharges. Recently, the term ictal epileptic headache has been proposed in cases in which headache is the sole ictal epileptic manifestation Diagnosis requires the simultaneous onset of headache with EEG-demonstrated ictal discharges.     

A comparison of post-ictal headache between patients with occipital lobe epilepsy and temporal lobe epilepsy.

We investigated post-ictal headaches (PIH) using a questionnaire to ascertain their characteristics and compare them among different types of epilepsy. The subjects consisted of 34 patients with occipital lobe epilepsy (OLE) and 75 patients with temporal lobe epilepsy (TLE). PIH occurred in 62% of OLE and 23% of TLE (P < 0.05). The quality of pain in PIH was 'steady' in 71% of OLE and 29% of TLE (P < 0.05) as opposed to 'pounding'. Other factors, such as frequency, severity, duration, and accompanying symptoms showed no significant differences. We found very few patients with migraine-like headaches. Analyses of clinical factors, such as age at onset, duration of epilepsy, seizure frequency, family history of headache, and interictal headache did not reveal any relationship to PIH, although generalized tonic-clonic seizures are associated with PIH in TLE (P < 0.05). These results suggest that the nature of PIH may be different between OLE and TLE, and that the region of epileptic focus or spreading area of epileptic discharge may have a close relation to the induction of PIH. An association with migraine, which has been reported previously, was unclear in our study.     

Ictal crying

PurposeThe purpose of this study was to describe a series of patients with ictal crying to estimate its occurrence and characterize the clinical features and the underlying etiology.MethodsWe retrospectively reviewed all the long-term video-EEG reports from Jefferson Comprehensive Epilepsy Center over a 12-year period (2004–2015) for the occurrence of the terms “cry” or “sob” or “weep” in the text body. All the extracted reports were reviewed, and patients with at least one episode of documented ictal crying at the epilepsy monitoring unit (EMU) were included in the study.ResultsDuring the study period, 5133 patients were investigated at our EMU. Thirty-two patients (0.6%) had at least one documented seizure accompanied by crying. Twenty-seven patients (26 women and one man) had psychogenic nonepileptic seizures (PNES), and five patients (0.1%) had epilepsy. Among patients with epileptic ictal crying, four patients had focal epilepsy (two had definite, and two had probable frontal lobe epilepsy), while one patient had Lennox–Gastaut syndrome.ConclusionIctal crying is a rare finding among patients evaluated at the EMUs. The most common underlying etiology for ictal crying is PNES. However, ictal crying is not a specific sign for PNES. Epileptic ictal crying is often a rare type of partial seizure in patients with focal epilepsy. Dacrystic seizures do not provide clinical value in predicting localization of the epileptogenic zone.     

Effects of the Anaesthetic-ECT time interval and ventilation rate on seizure quality in electroconvulsive therapy: A prospective randomised trial

BackgroundThe anaesthetic approach adopted in ECT practice has the potential to influence patient outcomes. However, the impact of the time interval between anaesthetic induction and ECT stimulus administration has not been studied prospectively to date. This variable may represent an indirect measure of anaesthetic concentration at the time of stimulation, and therefore may influence the quality of seizures induced.ObjectiveTo examine the impact of the anaesthetic to ECT stimulus time interval, and ventilation rate pre-treatment, on ictal seizure quality.MethodsIn a prospective, crossover trial, 54 depressed participants were randomised to variations in anaesthetic technique at four sequential ECT treatment sessions, in a 2 x 2 design: randomisation to a short or long anaesthetic-ECT time interval, and randomisation to normal ventilation or hyperventilation during anaesthetic induction with thiopentone. Ictal EEG data were collected at each study session and assessed by a blinded rater for ictal quality (seizure amplitude, regularity, post-ictal suppression and general seizure quality), using a quantitative-qualitative structured rating scale. Linear mixed effects models were used to analyse the effect of the anaesthetic-ECT time interval, and that of ventilation rate, on seizure quality indices.ResultsThe anaesthetic-ECT time interval had a significant impact on ictal EEG quality indices (p < 0.01), with longer time intervals producing higher quality seizures. Ventilation rate did not significantly influence quality measures.ConclusionThe time between anaesthetic induction and ECT stimulus administration has a significant impact on ictal EEG seizure quality. Conversely, manipulations of ventilation rate did not significantly affect seizure quality. These results suggest the anaesthetic-ECT time interval should be routinely monitored clinically and potentially optimised for maximising seizure quality with ECT.     

Post-epileptic headache and migraine.

One hundred epileptic patients were questioned about their headaches. Post-ictal headaches occurred in 51 of these patients and most commonly lasted 6-72 hours. Major seizures were more often associated with post-epileptic headaches than minor attacks. Nine patients in this series of 100 also had migraine: in eight of these nine a typical, albeit a mild, migraine attack was provoked by fits. The post-ictal headache in the 40 epileptics who did not have migraine was accompanied by vomiting in 11 cases, photophobia in 14 cases and vomiting with photophobia in 4 cases. Furthermore, post-epileptic headache was accentuated by coughing, bending and sudden head movements and relieved by sleep. It is, therefore, clear that seizures provoke a syndrome similar to the headache phase of migraine in 50% of epileptics. It is proposed that post-epileptic headache arises intracranially and is related to the vasodilatation known to follow seizures. The relationship of post-epileptic headache to migraine is discussed in the light of current ideas on migraine pathogenesis, in particular the vasodilation which accompanies Leao's spreading cortical depression.     

Seizure-related headache in patients with epilepsy.

We investigated the type and frequency of interictal primary headache and peri-ictal headache in 109 patients with partial-onset and 26 patients with generalized onset seizures in this study. Interictal headaches were present in 50 (40.7%) of 135 patients. Comparing the interictal headache on the basis of seizure type, we couldn't find any significant difference between the seizure groups. Seventy-nine (58.51%) patients had peri-ictal headache. Eleven of these patients had pre-ictal headache (PriH), three of all had ictal headache and, 56 of these had post-ictal headache (PoiH). PriH and PoiH were more frequently encountered before and after secondary generalized tonic-clonic seizures (GTCS) compared to other seizure groups. The type of pain in PoiH was 'throbbing' in complex partial seizures and 'steady' in GTCS.     

Peri-ictal heart rate variability parameters as surrogate markers of seizure severity

This study aims at defining objective parameters reflecting the severity of peri-ictal autonomic changes and their relation to post-ictal generalized electroencephalography (EEG) suppression (PGES), with the view that such changes could be detected by wearable seizure detection systems and prove useful to assess the risk of sudden unexpected death in epilepsy (SUDEP). To this purpose, we assessed peri-ictal changes in heart rate variability (HRV) and correlated them with seizure duration, intensity of electromyography-based ictal muscle activity, and presence and duration of post-ictal generalized EEG suppression (PGES). We evaluated 75 motor seizures from 40 patients, including 61 generalized tonic-clonic seizures (GTCS) and 14 other major motor seizure types. For all major motor seizures, HRV measurements demonstrated a significantly decreased parasympathetic activity and increased sympathetic activity in the post-ictal period. The post-ictal increased sympathetic activity was significantly higher for GTCS as compared with non-GTCS. The degree of peri-ictal decreased parasympathetic activity and increased sympathetic activity was associated with longer PGES (>20 s), longer seizure duration, and greater intensity of ictal muscle activity. Mean post-ictal heart rate (HR) was an independent predictor of PGES duration, seizure duration, and intensity of ictal muscle contraction. Our results indicate that peri-ictal changes in HRV are potential biomarkers of major motor seizure severity.