Barbara Chmielewska, Krzysztof Turowski

Headaches and epilepsy - interrelationships and differences

Chair and Department of Neurological Nursing,

Medical University of Lublin

Katedra i Zakład Pielęgniarstwa Neurologicznego,

Uniwersytet Medyczny w Lublinie

Barbara Chmielewska, Krzysztof Turowski

Headaches and epilepsy – interrelationships and differences

Bóle głowy i padaczka – współzależności i odmienności

Headaches and especially migraine are associated with a number of brain psychiatric and neurologic disorders, including depression and anxiety, strokes and epilepsies. Simultaneously both headaches and epilepsies are among the most common neurological diseases, mainly in pediatric population. Among headaches especially migraine present numerous similarities with epilepsy. These two conditions may be related in numerous ways although the nature of this relationship is still unclear and sometimes controversial. Both migraine and epilepsy are chronic disorders with transient paroxysmal episodes of altered brain function (consciousness) and often with prodromal symptoms of aura (tab.1, tab.2). They both affect otherwise healthy individuals. Fits of epilepsy and migraine may be triggered by stress, fatigue, hormonal fluctuations, light stimulation or alcohol consumption. Some of epilepsies as well as migraine have a genetic component and they are originally experienced between infancy and adolescence. However migraine is common (10% prevalence) while epilepsy rare (about 1%) and prevalence of migraine is low in childhood, peaks in adult age and decrease in old age, whereas the incidence of epilepsy is highest in childhood and then in an old age. Clinically based hypothesis that migraine and epilepsy are related dates back to the 19th century, despite the fact that W.R. Gowers in 1904 y. gave migraine a place in the borderland of epilepsy (“near it, but not of it”) and stressed that distinction between the two conditions might be problematic because epileptic seizures and migraine attacks might be mistaken one for the other. Gowers noticed that one disorder may develop while the other goes on in the same individual but he did not stress that one provokes the other [1]. However clinically well-known phenomenon that migraine-like headaches are common in the course of seizure fits and migraine attacks may trigger epileptic seizures resulted in distinguishing the entity presently known as migralepsy.

The term migralepsy was introduced in 1960 by Lennox and Lennox to describe an overlapping condition wherein migraine with aura is followed by symptoms characteristic of epilepsy. Subsequently, migralepsy defined as migraine-triggered seizures was included in the current International Classification of Headache Disorders II in 2004 y[2].

Epidemiological investigations showed the epilepsy prevalence of 5,9% (range 1% - 17%) in the population of migraineurs greatly exceeds the general population prevalence of 0,5%. The migraine prevalence in epileptics is also high and ranges between 8% and 23%. The relative risk for migraine in persons with epilepsy was 2,4 for both subjects and their relatives. The risk of migraine was elevated in both partial and generalized seizures and in both idiopathic and symptomatic epilepsies (particularly in post-traumatic epilepsies the risk was greater - 1,8, as compared with idiopathic or cryptogenic epilepsies)[3]. Greater risk of migraine was not related to age of epilepsy onset and seizure type. In pediatric studies, the prevalence of epilepsy was also significantly higher than in subjects without epilepsy (82% v.52%), and children with epilepsy had a 4,5-fold increased risk of developing headaches of different types [4]. Detailed epidemiological analyses elucidated possible association between migraine and epilepsy and showed that it is complex and multifactorial. This association include the following relationship: 1/shared the same underlying etiology - environmental or genetic risk factors, 2/ causally related - one condition leading to the other and 3/ random co-occurrence of the two diseases by chance and independently in the same individual [3].

Terminological aspects of association between headache and epilepsy. It was confirmed in multiple clinical observations that these two disorders may exist independently or epilepsy may initiate headache as well as migraine may trigger epilepsy. It is also well known that seizure and headache may be associated in certain primary or secondary neurological syndromes as occipital epilepsies or benign Rolandic epilepsy and inherited (e.g. neurofibromatosis) or accused (posttraumatic) lesions of occipital lobe (tab.3). In relation to time headaches may be clinically observed as appearing before epileptic fit, during the fit or as a post-ictal phenomenon. In more detailed descriptions these headaches are divided into two groups: 1. peri-ictal headaches: a/ pre-ictal, b/ ictal and c/ postictal and 2. interictal headaches. Pre-ictal headaches occur in about 5-15 % of cases, ictal in 3-5% and postictal in 10-50%. Interictal headaches concern about 25-60% of cases [5] (tab 4). First of all peri-ictal headaches, and among them ictal ones may be underestimate because of the dramatic clinical manifestation of seizure the same. Current International Classification of Headache Disorders (ICHD-II) divides headache disorders into two groups: primary and secondary (symptomatic). In the primary headache disorders, the headaches does not have an identifiable cause and are divided into four categories: migraine, tension type-headache, the trigeminal autonomic cephalalgias, and a group of headache disorders, analogous to the idiopathic epilepsies [6]. The chapter of migraine divides the entity into six subtypes, and among the complications of migraine it concerns migraine triggered seizures (tab.5). In general updated version of the Classification of Headache Disorders (ICHD-II) published by International Headache Society in 2004 distinguished three specific entities of headache-related seizures: migraine-triggered seizure (migralepsy), hemicrania epileptica and post-ictal headache (tab.6) [6]. This classification was lately postulated to be supplemented with the new disorder - ictal epileptic headache. Among essential criteria the authors indicate: headache as a sole epileptic manifestation lasting minutes-days who is ipsilateral or contralateral to lateralized ictal epileptiform discharges in EEG as well as an evidence of epileptiform (any localized or generalized) discharges on EEG and concomitantly with headache. Essential feature is that headacheas as well as EEG abnormalities should resolve immediately after iv antiepileptic medication (tab.7)[5].

Characteristics of headaches attributed to epileptic seizures

Migraine-triggered seizures or so-called migralepsy means a seizure triggered by migraine attack (tab.5, tab.6). Depending on the time relationship migralepsy has been considered as a form of pre-ictal headache. Migralepsy is a historical term that describe a condition wherein migraine with typical aura of ophthalmic and autonomic symptoms (nausea and vomiting) was followed by symptoms characteristic of epilepsy [1]. In other words migralepsy means an entity in which two separate disorders occur in succession. This term was accepted by International Headache Society in 2004. According to ICHD-II the diagnosis require migraine with aura and seizures fulfilling criteria for one type of epileptic attack that occurs during or within one hour after a migraine aura (tab.6). This definition sets that seizures are the sequence of specific headache type and they happen during migrainous aura. In this sense the definition places seizures among complications of migraine. Migralepsy is a rare condition; as yet about sixty cases and some reviews have been published. Most of case reports have been criticized as describing complicated and unequivocal disorders or they there in fact erroneously recognized occipital epilepsies [7].Taking into account the current ICDH-II statements only 4% among fifty published cases properly met criteria of migralepsy. Similar symptoms of epileptic aura (visual phenomena, headache) and essential seizure and migraine attacks may be mistaken one for the other or they can overlap. In particular insufficiently understood symptomatology of occipital seizures may be erroneously interpreted as visual aura of migraine. Reports have even described status epilepticus in partial occipital lobe epilepsy that was interpreted as migrainous status [8,9]. It is widely postulated to revise migralepsy as a separate disease entity. As yet this term could be taken into account in cases when a fit starts with an ictal epileptic headache followed by a sensory or motor partial and/or generalized seizure. Sporadically, headache per se may represent an epileptic seizure and the sole manifestation of epilepsy [9].

Hemicrania epileptica means an attack of hemicranial pain that occurs synchronously with seizure of partial characteristics. Headache presents migrainous features. This phenomenon is accompanied by ipsilateral EEG discharges [10]. According to ICHD-II classification four essential features that allow for recognition of hemicrania epileptica include: 1. headache lasting seconds to minutes, with feature of migraine, 2. the patient is having a partial epilepsy, 3. headache develops synchronously to the seizure and it is ipsilateral to the ictal discharges (diagnosis requires the simultaneous onset of headache and epileptic discharge in EEG recording), 4. headache resolves immediately after the seizure (tab.6). The phenomenon of hemicrania epileptica is rare. Detailed analysis of reports revealed that epileptic fits presented features of status epilepticus (nonconvulsive or complex partial) and headache (who completed immediately after the seizure) lasted several hours [9]. At present it is suggested that ictal headache can rarely be the sole ictal epileptic manifestation, without any other associated ictal epileptic signs and then the term ictal epileptic headache should rather be applied to describe this distinct disorder (clinical characteristics mentioned above) [5].

Ictal epileptic headache

Even from the clinical point of view this type of headache is distinctly different from both migralepsy and hemicrania epileptica because specific headache pattern is not required. Not only migraine with aura, but also migraine without aura as well as tension headache, and both idiopathic and symptomatic cases are all admitted. Headache is the only ictal phenomenon without any other associated ictal epileptic sign and symptoms who are recognized by International League Against Epilepsy. This is different entity from hemicrania epileptica who demand occurrence of partial epileptic seizure, sensory or motor [11, 12]. It is believed that this kind of headache has an autonomic nature (i.e. cephalic pain). Ictal epileptic headache is usually orbital or manifest as discomfort that does not have a clear localization. On the other hand ILAE classification defines, among the terms used to describe semiology of epileptic seizures, a “headache“ as a cephalic sensation in the head that is different from somatosensory (tingling, numbness, sense of movement) and autonomic seizures (distinct alteration of the cardiovascular, gastrointestinal or thermoregulatory function). Cortical spreading depression seems to be connecting point between migraine and epilepsy. It has been hypothesized that cortical spreading depression and cortical epileptic focus might trigger each other thus inducing attacks. Studies have shown that headache attacks can originate at cortical or subcortical level, whereas epileptic focus arises only cortically but can be subcortically modulated. The central autonomic system have a lower threshold for epileptic activation than the network producing focal epileptic sensory-motor symptoms. On the other words, the threshold required for the activation of cortical spreading depression (resulting in headache) is lower than that required for occurrence of epileptic seizure. In this way, the onset of epileptic seizures may subsequently activate the cortical spreading depression. Cortical epileptic discharges (insufficient to cause typical clinical manifestation of seizure) might activate the trigemino-vascular system and this stimulation results in migrainous headache as the sole clinical manifestation without any other epileptic symptoms of cortical origin [13]. These rare cases of ictal headaches (in fact - cases of autonomic epilepsy) are postulated to be separately classified as ictal epileptic headaches [12,13]. Accordingly, cases with long lasting ictal epileptic headache episodes fulfill the criteria to be considered as autonomic status epilepticus [14]. It is supposed that prevalence of this entity is underestimated as it is often unrecognized, and from eighties until now was described only a dozen cases [5,10]. In patients with the complaints of migraine-like headache “ictal” EEG recording can be helpful do determinate proper diagnosis. However is should be remembered that EEG patterns showed no specific characteristics and both focal rhythmic activity, lateralized and generalized spike-and wave or polyspike-and wave have been registered. The observed EEG patterns mostly included: rhythmic, high-voltage alpha activity with spikes or high-voltage theta activity with sharp waves over occipital or temporo-occipital region or even bilateral continuous spike and slow wave discharges [9,10,12]. In some cases photic stimulation can reveal photoparoxysmal EEG response as well as simultaneous complaints about pulsating headache. Therefore EEG confirmation should not be a decisive criterion as in some clinically verified patients it was not possible to detect any ictal epileptiform activity. In some but not all of these cases MR neuroimaging revealed secondary brain lesions in occipital or temporo-parieto-occipital region, and functional DWI-MR pointed restricted diffusion in the occipital region. It is worth noting that complete remission of the headache and of the epileptic abnormalities in most patients with presumed ictal epileptic headache was achieved not by means of specific anti-migraine or anti-headache drugs but following intravenous administration of anti-epileptic drugs-diazepam or phenytoin (5,9). As yet this specific entity was not included neither in the classification of the International Headache Society nor the International League Against Epilepsy. It is suggested to include ictal epileptic headache to the current ICHD-II classification in the group of headache-related seizures [5,9,11]. Proposed diagnostic criteria are listed in table 7.

Postictal headache is a headache who starts immediately after cessation of seizures. This the most frequent type between seizure-associated headaches occurs in about 50% (or even in 62% of young population) of the epileptic patients (tab.4) [15]. Post-ictal headache has been included in the current ICHD-II. Diagnostic criteria are as follows: a/ headache with features of tension-type or migraine (in patients with migraine), b/ the patient has had a partial or generalized epileptic seizure, c/ headache develops within 3 h following the seizure, d/ headache resolves within 72 h after the seizure (tab.6). Clinical analysis of post-ictal headaches in 372 epileptic patients revealed that 45% had experienced postictal headaches, a half of them always had headaches and they were severe in 39% individuals. 27% of patients had independent headaches that were similar to their seizure-related headache. Headaches lasted less than 6 h in 81% and more than 24 h in 8% and they were throbbing in over two thirds [16]. Another analysis reported 51% of epileptic patients with postictal headache, and more frequently associated with generalized tonic-clonic than with focal seizures. Every tenth patient also had independent migraine attacks. Postictal headaches were either uni- or bilateral troubling aches, with visual aura, with phono- and photophobia as well as nausea or vomiting and lasted 6 to 72 hs. Interestingly, in migrainous patients headaches were similar to their migraine attacks and similarly responded to triptans [17]. While pre-ictal and ictal headaches are relatively rare and short lasting, in contrast, post-ictal headaches are common and can impact on quality of life of the persons with epilepsy. Post-ictal headache is most common with generalized clonic-tonic seizures but is also common in complex partial seizures and less common with simple partial seizures [16]. Post-ictal headache has been reported in patients with symptomatic epilepsy but it is mainly recognized in idiopathic occipital epilepsies [17]. It is suggested that the seizure discharges in the occipital lobe trigger a migraine headache through cortical, trigeminovascular and brainstem mechanisms (similarly to the mechanism of an ictal epileptic headache) [1,12,13,17].