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Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, “G. Gaslini” Institute, Genoa, Italy
Headache may be the only clinical ictal manifestation of an epileptic seizure.
The latter condition is now classified as “Ictal Epileptic Headache” (IEH).
EEG is not recommended as a routine examination for children diagnosed with headache.
However, ictal-EEG recording should be performed in cases of unresponsive headache.
IEH should be considered before suspending therapy to avoid risks in epileptic children.
When we published the diagnostic criteria for “ictal epileptic headache” in 2012, we deliberately and consciously chose to adopt restrictive criteria that probably underestimate the phenomenon, rather than spread panic among patients and physicians who are reluctant to accept this entity.
Here we discuss four intriguing clinical cases to highlight why we believe, to this day, that it is necessary to follow these restrictive diagnostic criteria.
EEG is not recommended as a routine examination for children diagnosed with headache, but it is mandatory and must be carried out promptly in cases of prolonged headache that does not respond to antimigraine drugs, if epilepsy is suspected or has been diagnosed previously. This is not a marginal or irrelevant question because possible isolated, non-motor, ictal manifestations should be taken into account before declaring that an epileptic patient is “seizure free” so as to ensure that any decision taken to suspend anticonvulsant therapy is safe.
] (Table 1) . It has been stressed that IEH criteria probably underestimate the true incidence and prevalence of this epileptic phenomenon and that the old concept of migralepsy (an event that is unlikely to exist) should be abandoned [
]. Indeed, “migralepsy” should be considered as a seizure from the very beginning, starting with the onset of an “ictal epileptic headache” immediately followed by other (sensory-motor or autonomic) ictal epileptic signs or symptoms [
Any localization (frontal, temporal, parietal, occipital) is admitted.
lateralized or generalized) discharges on scalp EEG concomitantly with headache; different types of EEG anomalies may be observed (generalized spike-and-wave or polyspike-and-wave, focal or generalized rhythmic activity or focal subcontinuous spikes or theta activity that may be intermingled with sharp waves) with or without photoparoxysmal response (PPRs)
D. Headache resolves immediately (within few minutes) after i.v. antiepileptic drugs
a A specific headache pattern is not required (Migraine With or Without Aura, or Tension-type headache are all admitted).
b Any localization (frontal, temporal, parietal, occipital) is admitted.
To further stress the extent to which the IEH phenomenon may be underestimated, we describe and discuss four children, aged 7, 9, 12 and 13 years, who first presented a headache (probably an IEH) and were subsequently diagnosed as being affected by epilepsy. The first episode in three of these children had been diagnosed as a “migraine attack” with acute onset months, or even years, before the onset of the first recognized generalized tonic–clonic epileptic seizure. In the youngest of these three children, an autonomic status followed by a tonic seizure after an “episode of migraine” was also recorded. In the fourth case, a very short headache that had occurred two months before the seizure was interpreted erroneously as an expression of anxiety. Since the most important IEH criterion (clinical-EEG remission following i.v. AED administration) in the four cases described here was not fulfilled, as is instead required according to the published criteria, a diagnosis of IEH could not be made. However, our hypothesis of “probable” IEH cases is supported by the fact that in three of the children we recorded an EEG during the “headache” episodes. The close electro-clinical correlation of the brief episodes in the remaining case leaves no doubt as to their epileptic origin.
Here we also briefly discuss the previously published cases and related criteria for IEH diagnosis, once again stressing that the IEH may be an underestimated phenomenon that precedes (especially in children owing to the greater difference in this period of life between the activation threshold required for the autonomic and non-autonomic neural networks [
]) the onset of a recognizable “epileptic seizure” characterized by other autonomic or sensory-motor ictal signs, whether they are or are not associated with IEH episodes.
2. Four intriguing clinical-EEG cases: strengths, weaknesses and pitfalls of the IEH criteria
2.1 Case 1
A nine-year-old boy had been suffering, since the age of six, from headache with a frequency of less than one attack per month. Headache was described as a long-lasting frontal pain of severe intensity, sometimes accompanied by paleness and feeling of sickness, that appeared in the morning and only ceased during nocturnal sleep.
At the age of eight years, during one of his apparently “usual” headache episodes, some hours after the onset of pain, the mother noticed the child suddenly becoming paler, keeping the saliva in his mouth (“he moved it from side to side as if he was playing with it”); at the same time he became more quiet, less responsive, giving “strange answers” to questions, even though he continued to be fairly well oriented and conscious. The child was examined at the Emergency Room, where his symptoms were diagnosed as a “migraine attack”. No family history of epilepsy or migraine was reported. Psychomotor development was normal, as was the neurological examination. Two similar episodes occurred three and six months later in the afternoon during a headache episode; the symptoms disappeared after a three-hour sleep without the need for any medication. An EEG, performed the day after the second episode, was reported to be normal, as was a brain MRI.
At the age of nine years, the child was admitted to our Paediatric Emergency Department, in the afternoon, for an episode characterized by headache that had started early in the morning. The neurological examination was normal. Ibuprofen (10 mg/kg) was administered and the boy fell asleep 10 min later for about two hours. When he woke up, the headache was still present but was now associated with pallor and hyper-salivation. After 10 min, the boy suddenly opened his eyes, after which upward eye deviation, head deviation to the right and, lastly, tonic posturing occurred; all these symptoms disappeared after rectal diazepam (10 mg) administration. Although the neurological examination was again normal, the boy was admitted to the Paediatric ward to undergo further investigations.
All the blood, cerebrospinal fluid and metabolic investigations performed in the Pediatric Emergency room were normal (only serum lactate was increased by 35 mg% in the peripheral venous sample during the ictal phase), while his blood pressure, which had risen slightly during the ictal period (BP = 125/75), returned to normal some hours after the ictal phase.
For the rest of the day after, he suffered from his apparently “usual” headache episode, which did not respond to Ibuprofen (10 mg/kg). That evening, when he still had a headache, an EEG performed during sleep revealed a brief subtle seizure characterized only by tachycardia and rare functional multifocal spikes, located mainly in the central areas and on the vertex (Fig. 1).
All the other blood routine laboratory examinations and additional metabolic investigations performed during hospitalization were normal, as was a brain MRI. After being placed on topiramate per os therapy (3 mg/kg/day, per os), the patient did not report any headaches or ictal epileptic events at the 18-month clinical-EEG follow-up.
2.2 Cases 2 and 3
As cases 2 and 3 were highly similar, they are described together here. Both the boys (at the age of 12 years in case 2, 13 in case 3) were admitted to our Pediatric Emergency Department for a long-lasting headache that was unresponsive to Ibuprofen (10 mg/kg) and paracetamol (15 mg/kg) therapy. Psychomotor milestone development and the neurological and psychiatric examinations were normal in both cases, as were the brain MRI investigations performed upon admission to Pediatric Emergency Room. No family history of epilepsy was reported, although the father in case 2 and the mother in case 3 had a history of migraine without aura that did not respond to anti-migraine therapy.
The parents in both cases reported a history (starting at the age of seven in case 2 and nine in case 3) of drug-resistant, long-lasting headaches with stereotyped manifestations (characterized by fronto-temporal pain of severe intensity accompanied by photophobia, phonophobia and occasionally vomiting) with a frequency of approximately two or three attacks per month.
In both cases we were able to record, upon admission, an EEG during the final part of these long-lasting headache episodes (Fig. 2a for case 2 and Fig. 3 for case 3). We detected EEG abnormalities in the occipital regions in both cases (Figs. 2a and 3). In both cases parents refused intravenous antiepileptic drugs, so we could not be able to make a diagnosis of “Ictal Epileptic Headache”, according to the published criteria [
All the blood and metabolic investigations performed in both children were in normal range, while their blood pressure, which had risen slightly during the ictal period (BP = 125/80 in case 2, and 130/85 in case number 3), returned to normal some hours after the ictal phase.
The parents of both boys refused hospitalization of their children. In the following months, both boys continued (two–three attacks per months) having similar long-lasting (hours) headache episodes that were unresponsive to anti-migraine therapy.
After 9 months (case 2) and 13 months (case 3), both children had their first generalized tonic–clonic epileptic seizures preceded in both cases by the aforementioned “usual” episodes of headache. In both cases, valproate therapy (10 mg/kg/day, per os) led to complete control of the clinical picture (with no occurrence of headache and/or seizures). To date, two years later, the boys are still headache- and seizure-free, with normal EEGs (see Fig. 2b).
2.3 Case 4
A seven-year-old girl was referred to our hospital following a seizure accompanied by loss of consciousness and axial tonic posture lasting a few seconds. The episode occurred while the girl was playing a videogame. She was held by her father during the episode and did not consequently fall. Upon admission, her father told us that two months earlier the girl had started complaining of daily episodes of a sudden throbbing unilateral, or bilateral, brief temporal headache. On such occasions, she turned pale and displayed discomfort. The father had interpreted these manifestations as an expression of anxiety and reassured the girl whenever they occurred. In the same period, the car sickness the girl normally suffered from worsened, invariably triggering a headache followed by nausea and occasionally vomiting. Psychomotor development and the neurological examination were normal.
The interictal EEG revealed focal paroxysmal abnormalities in the right fronto-temporal regions. The episodes of headache were recorded during a long-term video-EEG monitoring which was performed to capture the daily episodes of brief throbbing headache. The recording allowed us to document their epileptic origin (Fig. 4). A brief diffuse sequence of rapid small amplitude activity, followed by slow rhythmic waves in the right temporal areas on the EEG was associated with a passing expression of discomfort and complaints of a headache (Fig. 4).
All the blood, cerebrospinal fluid and metabolic investigations performed were normal, while the blood pressure, which had increased slightly during the ictal period (BP = 125/75), returned to normal a few hours after the ictal phase.
Antiepileptic treatment with oxcarbazepine was started. The girl complained of other headaches that gradually decreased during titration. Once the therapeutic range of oxcarbazepine was reached, the girl only occasionally complained of car sickness. The EEG also returned to normal. Three months later the girl once again started complaining of more frequent headache attacks and EEG focal paroxysmal activity reappeared. An MRI examination performed following these two findings revealed a right temporal intracortical lesion with the features of a dysembryoplastic neuroepithelial tumor (DNET). Since complete seizure control was achieved in the patient, the parents refused to give their consent to a neurosurgical operation to remove the DNET lesion, and the girl is currently still seizure- and headache-free.
3. Discussion of the four clinical-EEG cases
The first symptoms in all four children were headaches, accompanied by paleness and nausea in case 1, by paleness and apparent discomfort in case 4, and by no other signs/symptoms in the other two cases (2 and 3). The first generalized tonic–clonic epileptic seizures in cases 2 and 3 occurred after 9 and 13 months, respectively, and were preceded in both cases by the aforementioned “usual” episodes of headache.
In case 1, autonomic manifestations associated with reduced responsiveness appeared later. The subjective features of the headache did not change from the first to the last episodes in the child description (see description of the cases). The symptoms in the girl in case 4 started with a brief daily headache and paleness, followed two months later by an epileptic seizure with a tonic axial component.
In order to make a diagnosis of IEH, one must be able to demonstrate a condition in which a headache is the only ictal clinical sign of an epileptic seizure, is synchronous with an EEG discharge, and is responsive (from both the clinical and EEG points of view) to i.v. AED administration. According to the proposed criteria, IEH can last seconds, minutes, hours or days, and must be resolved by i.v. antiepileptic medication [
]. Obviously, if the IEH event only lasts a few seconds, as is likely to happen in the vast majority of such cases, it will be impossible to document the synchronous clinical-EEG response to i.v. AED administration. This is but one of the unavoidable pitfalls and weaknesses linked to the proposed criteria. In fact, it was unfortunately impossible to evaluate the efficacy of possible i.v. antiepileptic medication in cases 1, 2 and 3: in case 1 we had no opportunity to test i.v. AED administration before starting per os anticonvulsant therapy, whereas in cases 2 and 3 the children's parents refused to allow i.v. AED administration during the “ictal epileptic headache” recording (see Fig. 2, Fig. 3). In case 4, the short duration of the seizures we observed and recorded prevented us from testing the response to i.v. AED administration.
According to the ILAE (International League Against Epilepsy) nosography, the stereotyped sequence of the episodes of paleness, hypersalivation and hyporesponsiveness lasting about 30 min in case 1 may be interpreted as signs of an autonomic seizure (autonomic status). Indeed, the event ended in motor symptoms, which are an expression of the propagation of the ictal epileptic discharge. Moreover, the electrical ictal discharge and the time-locked tachycardia highlighted by the polygraphic EEG sleep recording (Fig. 1) may be regarded as a possible “subtle” autonomic seizure. In this regard, it has previously been suggested that the IEH phenomenon be classified among “autonomic seizures”, as happens for Panayiotopoulos syndrome [
] that the age-specific lower activation threshold of the autonomic system (“the younger, the more autonomic”) may explain the possible isolated headache manifestation during an epileptic seizure, as occurs in autonomic ictal manifestation for Panayiotopoulos syndrome in children [
In addition, in case 1 there is ictal sleep-EEG documentation of autonomic seizures and status, recorded immediately after a long-lasting headache (lasting the whole day that preceded the sleep EEG recording). This allows us to hypothesize a diagnosis of long-lasting headache at the seizure onset, followed sequentially by other autonomic manifestations.
A good response to AED/per os therapy and a positive outcome was achieved in all four cases, with complete clinical-EEG remission of the picture (headache- and seizure-free) even after two years of follow-up. In case 1 we may, however, hypothesize a long-lasting ictal headache at the onset of the seizure followed by other signs/symptoms, which prevented us from making a diagnosis of IEH (see criteria). On the other hand, bearing in mind the personal history (numerous episodes of long-lasting stereotyped headache not responsive to anti-migraine drugs) in case 1, we cannot rule out that an “IEH” might sometimes have occurred.
The picture in cases 2 and 3 is more straightforward as we were able to record the final part of a possible IEH (see Fig. 2, Fig. 3) which could not, however, be documented (owing to the parents’ refusal) due to clinical-EEG response by i.v. AEDs administration. In any case it is highly suggestive that both the children (see cases 2 and 3) displayed the first TCGS after a long-lasting headache months later (9 and 13 months, respectively) accompanied by the aforementioned clinical characteristics, with complete remission (of both the headache and epileptic seizures) after continuous per os AED therapy.
In case 4, headache was the only symptom of most of the seizures. During the EEG ictal activity, the video recording only revealed a slight frowning that we interpreted as the initial sign of an unpleasant, painful sensation of which the girl complained a few seconds after the first EEG modification. Consciousness was not impaired. All the seizure resolved spontaneously within seconds and i.v. AED administration was not required. There have been reports of painful epileptic seizures giving rise to cephalic pain, with the epileptogenic zone being localized in the contralateral parietal lobe or ipsilateral temporal lobe [
]. Ictal cephalic pain cannot share the clinical features of migraine owing to its short duration. In this case, knowing that even the isolated headache was an ictal epileptic headache (i.e. an epileptic seizure) allowed us to recognize that the girl's epilepsy was not under control; this is a crucial aspect, not a marginal or irrelevant question.
] that the activation threshold for cortical spreading depression (CSD) is inferior to that required for an epileptic seizure. This theory would explain why epileptic patients presenting a peri-ictal headache are seen considerably more often than migraine patients presenting an epileptic seizure.
EEG usually plays a minor diagnostic role in the routine study of patients suffering from migraine. Conversely, the headache/migraine reported to be the only manifestation of a non-convulsive epileptic seizure in the patients described in the literature on IEH [
] was diagnosed exclusively on the basis of the EEG recording; the subsequent intravenous administration of anticonvulsant drugs in these patients was able to control the clinical-EEG picture (remission of both scalp EEG discharges and the headache). In addition, in two IEH cases described in the literature [
], the ictal EEG discharges were recorded purely by chance by means of deep electrodes being used for neurosurgical purposes. Therefore, even though EEG recording is not very useful as a screening instrument for migraine, it does play a fundamental role in pediatric patients who have headache/migraine symptoms that do not respond to commonly used anti-migraine drugs, particularly in the epileptic population.
In the literature, headache is rarely reported as the only ictal manifestation of an epileptic seizure, and in the few cases that do exist [
] headache (with prevalently, though not only, migraine characteristics) was the only clinical expression of a non-convulsive seizure state. In these patients with non-convulsive epileptic seizures, headache “as an isolated ictal epileptic manifestation” (see criteria for “ictal epileptic headache”) [
] was associated with a wide range of different EEG patterns. As far as the etiology is concerned, “ictal epileptic headache” in the literature was associated both with idiopathic and with symptomatic forms of epilepsy, as also emerges from the “probable IEH” cases presented and discussed here: case 4 may be a symptomatic form (with a DNET lesion at MRI), while the others (cases 1, 2 and 3) may be idiopathic cases.
As it regards the neuroradiological findings in IEH published cases, the literature data are scarce; in particular, diffusion-weighted MRI has identified signal alterations in the region of seizure activity [
] proposed diagnostic criteria for IEH (Table 1): (1) a headache lasting between minutes and days; (2) headache (if lateralized) can be ipsilateral or controlateral to the epileptic anomalies (if not generalized) recorded on the scalp EEG; (3) headache resolves immediately after intravenous administration of anti-epileptic drugs. IEH does not necessarily have the characteristics of migraine (with or without aura) or those of a tension-type headache; indeed, a wide range of clinical headache types have been described. In short, the crucial diagnostic features are, according to data in the literature [
], the clinical and EEG remission following intravenous administration of antiepileptic drugs.
As there are a very limited number of well-documented IEH cases in the literature, this clinical entity has only been cited in an appendix of the new ICHD-III classification, and will continue to be until more cases have been documented [
], we would also like to point out their inevitable drawbacks.
To date, headache and epilepsy classifications have ignored each other. In the ILAE classification, headache is considered exclusively as a possible semiological ictal phenomenon among the “non-motor” features.
Despite still being a controversial issue, we must consider that headache pain may originate in the terminal nervous fibers (“vasomotor”) in cerebral blood vessels; consequently, headache should be classified as an “autonomic” sensation in the ILAE Glossary and Terminology [
] previously suggested that an autonomic seizure (i.e. in IEH cases) remains purely autonomic if ictal neuronal activation of non-autonomic cortical areas fails to reach the symptomatogenic threshold, as previously described for other ictal autonomic manifestations in Panayiotopoulos syndrome [
An additional point that deserves attention is the lack of a clear, repetitive EEG headache-associated pattern. Indeed, the ictal EEG recording in such patients does not yield a particular EEG pattern [
] with specific cortical correlations (e.g. focal frontal, parietal, temporal, occipital and primary or secondary generalized), as has also been reported (confirming our point of view) for autonomic manifestations in children affected by Panayiotopoulos syndrome. Lastly, the criteria we propose do not offer the possibility of confirming all suspected cases of IEH by means of intravenous anticonvulsant drug administration, just as it is not always possible for other types of epileptic seizures (as it can happen, for example, in cases of prolonged unresponsive seizures or even refractory status epilepticus).
For all the above reasons, we firmly believe that the diagnosis of IEH (even according to our proposed new criteria) will remain an underestimated phenomenon owing, in particular, to:
the psychosocial stigma attached to this disease;
the fact that IEH cannot always be detected from the scalp by EEG recording;
IEH may occasionally be unresponsive to i.v. antiepileptic drug administration, as can happen for other type of seizures.
It is important to suspect, recognize and diagnose IEH, particularly in children, in order to avoid misdiagnoses, incorrect therapy and an excessive number of examinations.
IEH diagnosis (even according to our proposed new criteria) will remain an underestimated phenomenon and the four children here discussed are cases in point: although strongly suspected of having IEH, they do not fulfill the IEH published criteria [
In conclusion, EEG is not recommended as a routine examination for children diagnosed with headache, but should be considered mandatory and be carried out promptly in cases of a prolonged headache that does not respond to antimigraine drugs, particularly if epilepsy is suspected or has been diagnosed previously.
Lastly, this is not a marginal or irrelevant matter because these possible, isolated, non-motor, ictal manifestations need to be taken into account before declaring an epileptic patient as “seizure free” so as to ensure that no risks are taken when anticonvulsant drug therapy is suspended.
Conflict of interest
We declare we have no conflict of interest or financial interest in publishing this article.
Kasteleijn-Nolst Trenite D.G.A.
“Ictal Epileptic Headache”: recent concepts for new classifications criteria.