Migralepsy is defined as a migraine triggered seizure , however the relationship between the two clinical entities is complicated. The term ‘migralepsy’ was introduced by Lennox and Lennox in 1960. It is a term used to describe a syndrome wherein ophthalmic migraine i.e. migraine with aura is followed by symptoms characteristic of epilepsy [2,3].
It is difficult to make a definite diagnosis of migraine (phenotypically heterogenous) as there are no objective tests and markers. This has resulted in a marked variability in prevalence studies. Migraines affect 15% of the population, with females having a greater prevalence than men , mostly aged 35-45. Epilepsy is estimated to occur in 1 in 26 people, with the incidence being highest in the first year of life and over the age of 75 .
Among epilepsy patients the prevalence of migraine is 7-26% and in migraine patients, epilepsy was prevalent in 1-17% . With both conditions being common, there has been evidence to back up the assumption that migraines and epilepsy are co-morbid conditions. Ottman et al illustrated that the rate of migraines was significantly higher in patients with epilepsy (26%) and their relatives with epilepsy (24%) compared with the relatives without epilepsy (14%), with the relative risk being 2.4 . Children with benign rolandic epilepsy have been shown to have increased risk of migraines as demonstrated by Giroud et al compared with children with absence epilepsy, partial epilepsy and head trauma . However, Wirrell found there was no statistically significant difference between benign rolandic epilepsy compared with cryptogenic partial epilepsy . Similarly, juvenile myoclonic epilepsy is also associated with increased incidence of migraine, a RR of 4.4 . Ludvigsson found that a history of migraine with aura was a risk factor for
developing epilepsy whilst migraines without aura did not have the same association . Findings have not been consistent across all studies. Ottman, et al.  surveyed 2000 patients with epilepsy and their families and failed to show patterns of migraine and epilepsy. Another study in Norway did not demonstrate a significant correlation between epilepsy and migraine.
A common underlying mechanism has been suspected as many diseases are expressed as both seizures and headaches. Mitochondrial diseases in particular MELAS and POLG1 mutations can manifest with both epilepsy and migraines. In MELAS, the posterior cerebral region is preferentially affected  whilst POLG1 mutations result in epilepsy affecting the occipital lobe . Damage in these regions may be related to the development of migraines. Familial hemiplegic migraine has been linked with mutations in the CACNA1AM, ATP1A2 and SCN1A channels; these are also closely linked to epilepsy .
Cortical spreading depression (CSD) was a concept initially proposed by Lashley in 1941. In the 1970s, glutamate released from glial cells was recognized as triggering CSD . Although the mechanism and spread of CSD is not fully understood, the concept of hyper-excitability and synchronicity is basis for a common mechanism between epilepsy and migraines to exist. It has been hypothesized that seizure discharges in the occipital lobes trigger a genuine migraine headache through cortical spreading depression (CSD) leading to activation of the trigeminovascular system or brainstem mechanisms without any other associated cortical epileptic sign, as suggested previously . The central autonomic systems; whether cortical or subcortical, have a lower threshold for epileptogenic
Keywords: Migralepsy, Seizure, Syndrome, Symptoms, Cortical spreading Depression, Semiology, Seizures, Topiramate, Sodium, Gabapentin, Pregabalin, Zonisamide, Zig zag patterns, Temporo-occipital Regions, Bilateral, Drugs, Brain, Epileptic Headache, Children, Rolandic Epilepsy
Abbreviations: CSD: Cortical Spreading Depression; ILAE: International League Against Epilepsy activation than those that produce a focal cortical sensory-motor
semiology. This may explain why it is more likely to observe
epileptic patients with post-ictal headache rather than migraine
subjects with epileptic seizures  as the onset of seizures may
lead to the onset of CSD to a greater degree as compared with the
onset of CSD leading to seizures.
As AEDs can be used to prevent migraine, this further
emphasizes a shared pathophysiology. Topiramate and Sodium
Valproate are perfect examples of drugs that are also used for
migraine prophylaxis as well as gabapentin and pregabalin.
Zonisamide and levetiracetam have also been used in some case
series reported. On the other hand, many AEDs are ineffective
in preventing migraines suggesting alternative mechanisms to
initial hyper-excitability may play a role.
Occipital lobe epilepsy, primarily occurring in children,
often presents as headaches as part of the ictal semiology.
Visual auras and ictal headaches are not exclusive to occipital
epilepsies. Panayiotopoulos hypothesized occipital lobe
seizures triggered migraines by activating trigeminovascular or
brainstem systems as discussed previously . He describes
visual symptoms which were distinct from migrainous auras,
but postictal headaches consistent with migraine headaches.
He also concluded that the quality of the visual aura could help
distinguish between the two clinical entities. Elementary visual
hallucinations were unique to epilepsy whilst wavy lines, zig
zag patterns were well described migrainous auras not part
of epilepsy aura. Epileptic visual auras were also noted to be
shorter in duration.
Marks studied 79 patients with epilepsy and migraine;
identifying  patients whose seizures and migraines
were temporally related. In 5 of these patients, EEG showed
periodic lateralized epileptiform discharges that resolved with
the headache. Small case series and some case reports have
demonstrated examples of patients with seizures triggered by
migraine. Niedermeyer described 8 patients with generalized
tonic clonic seizures occurring with migraines with preceding
visual auras . Interictally, imaging, examination and
neurophysiology were all essentially normal. A positive family
history of migraine was also associated and poor responses to
migraine and epilepsy drugs were noted. Colombo et al reported
a case of migralepsy meeting the ICHD-II definition; the patient
suffered a GTCS following a typical migrainous aura . An
EEG obtained at the time showed right temporal epileptiform
discharges, which normalized when the headache was not there.
Topiramate was started to good effect.
Migralepsy has also been described without symptoms of
aura. Freidenberg discusses a case where the patient suffered
a GTCS during a typical migraine without aura . The patient
suffered a seizure arising from sleep after the 4th day of
headache and left visual neglect. The MRI showed enhancement
in the right parieto-occipital region, which resolved on repeat
imaging. Verotti, et al.  summarized 16 potential cases in a
multi centre review. Many of these cases did not meet the ICHDII
definition and did not have sufficient EEG data to rule out ictal
headache. These cases demonstrated a female predominance
but no consistent seizure localization or EEG pattern .
The author argued that these cases support a diagnosis of
ictal headache, without any EEG representation, and the need
for a greater understanding is needed before migralepsy can
confidently be its own entity .
Migraine is listed in ‘the Borderland of epilepsy’. Gowers
recognizes that migraine ‘hemicrania’ is difficult to differentiate
from epilepsy. He also stresses two symptoms that are
particularly discriminative; migraine headache is much more
severe than postictal headache and visual symptoms are short in
epilepsy and long in migraine. Panayitopolus concluded that the
duration of visual symptoms is key in recognizing whether the
symptoms are related to migraine or occipital lobe epilepsy even
if these are not followed by headache or an epileptic seizure
More commonly epilepsy rather than headache specialists
show interest in migralepsy. Despite this, migralepsy as such
appears in the headache classifications and not in epilepsy
classificiations [3,20]. Migraine triggered seizures have
been included in the ICHD-II as a complication of migraine,
whilst international league against epilepsy (ILAE) seizure
classification does not mention migralepsy at all. The 2013
international classification of headache disorders included
migraine aura triggered seizures; which required ‘migraine
fulfilling criteria for migraine with aura’ and ‘a seizure fulfilling
diagnostic criteria for one type of epileptic attack and occurring
in a patient with migraine with aura, and during, or within 1
hour after, an attack of migraine with aura’ . However, the
international league against epilepsy proposed terminology for
seizures did not specifically include migralepsy as a seizure type
The concept of migralepsy as a migraine-epilepsy sequence
has been criticized by many authors as they felt most of the
cases reported did not follow an unequivocal migraine-epilepsy
sequence . They felt these were occipital seizures imitating
migraine with aura. Thus 2 out of 3 cases described by Lennox
seemed to have occipital epilepsy with visual hallucinations23.
Sances et al.  reviewed 50 potential migralepsy cases and
found only two cases met the criteria outlined by ICHD-II23.
They described a patient complaining of visual symptoms
associated with déjà vu sensation, olfactory hallucination lasting
about ten minutes, which developed into a GTCS. Although the
symptoms described are migrainous in origin, as confirmed by a
visual aura rating scale of 6, all of his symptoms as well as those
typical of visual aura, could have represented an epileptic aura
that may develop into a seizure.
Migraine and epilepsy have common pathophysiologic
mechanisms and share some defining characteristics; distinguishing them from other neurological disorders i.e. they
are both episodic2. However, on clinical grounds alone it can be
hard to differentiate between the two. Epileptic seizures and
migraine attacks may easily be mistaken for each other and can
overlap. There are marked difficulties in distinguishing epileptic
occipital aura from migraine aura especially if there is limited
history regarding the visual disturbance .
a. “Migraine visual aura starts as a flickering, uncoloured,
zig zag line in the centre of the visual field, progressing
over 4-30 min towards the periphery of one hemifeild,
and a scotoma often follows. The total duration is about 60
b. “Ictal elementary visual hallucinations of occipital
lobe epilepsies are mainly coloured and circular, develop
rapidly (within seconds), and are relatively brief (2-3 min).
They often appear in the periphery of a temporal hemifield,
widen and multiply during the seizure, and frequently move
horizontally towards the contralateral side”.
However, this is rarely clear in clinical practice. Visual
symptoms may be mixed, and brief visual seizures may
be followed by headache and vomiting, thus making them
indistinguishable from migraines. Alternatively, headaches
could be an ictal phenomenon [3,20].
The international classification of headache disorders
included the term hemicrania epileptica . Hemicrania
epileptica is recognized as an ipsilateral headache with migraine
features occurring as an ictal manifestation of seizures. Isler et
al.  found that hemicranial attacks of pain coincided with
seizures activity and lasted for seconds to minutes. Although
this condition is rare, it has been included in the ICHD-II =:The
diagnostic criteria included: “
1) headache lasting seconds to minutes with features of
2) the patient is having a partial epileptic seizure, and
a) headache has significantly improved immediately after
the partial seizure has terminated, or
b) headache is ipsilateral to the seizure discharge .
Diagnosis requires the simultaneous onset of headache with
EEG-demonstrated discharge . On the other hand, the 2001
international league against epilepsy glossary included ‘cephalic’
as a non-motor, sensory manifestation e.g. light-headedness,
tingling or headache .
A case series of 5 patients demonstrated migraine/headache
that lasted longer than ‘seconds to minutes’ and was the only
clinical manifestation of a non-convulsive status epilepticus
[24,27,28]. Of note, these patients did not meet the above
mentioned criteria for HE. Headache with migraine features is
a common post-ictal phenomenon occurring in 50% of patients
with epilepsy. This has also been included in the ICHD-II. Schon
and Blau reported 51% of epileptic patients having post-ictal
headache. PIH was linked more with GTCS than with focal
seziures. PIH has been reported more often in symptomatic
epilepsy but it is mainly observed in idiopathic occipital seizures
Both interictal and ictal EEG abnormalities in patients with
migraine consist mainly of asymmetrical theta bursts, located
over the temporo-occipital area. Patients with epileptic visual
symptoms may also show similar EEG abnormalities. EEG
recordings may thus only record theta or delta waves, reflecting
the subcortical abnormalities. Photophobia is mentioned only
sporadically in epilepsy; only about 5% have seizures triggered
by visual stimuli13. Occipital seizures can rapidly propagate to
the temporal lobes, explaining why parieto-occipital seizures
have predominant autonomic symptoms and can be mistakenly
diagnosed as migraine. A recent study by Toldo et al. showed that
56 of 1795 children had both headache and epilepsy, commonly
migraine. In 44%, the onset of epilepsy preceded headache, in
27% headache started first whilst in 29% both started in the
same year .
Chromosome 9q, 14q and 12q have been deliberated by
deprez and polvi [29,30]; the loci being linked to both epilepsy
and migraine, however to the present date no causative genes or
probability loci in ‘migralepsy’ have been identified.
Migraine as a sole manifestation of a seizure might be the
expression of a non-convulsive SE, which may only be diagnosed
by EEG recordings. High-voltage, rhythmic, 11-12 Hz activity
with intermingled spikes over right temporo-occipital regions,
high voltage theta activity, intermingled with sharp waves over
occipital region and bilateral continuous spike and slow-wave
discharges have been associated with IEH. In patients with IEH
it was noted a complete remission of the headache was obtained
with IV diazepam and not with antimigraine drugs. MRI brain
in these patients showed secondary brain lesions in the right
temporo-parieto-occipital region [2,28] with a restricted
diffusion in the right occipital region or enlarged sulci in the
right parietal region. Therefore, further research should be
done with MRI imaging in patients presenting with symptoms
suggestive of migralepsy; to be able to identify any characteristic
There is a role for 24-h video EEG telemetry recordings
as demonstrated by Mark and Ehrenberg. They looked at two
patients in which the entire migraine-epilepsy sequence was
captured, showing changes during the migraine that were
atypical for electrographic epilepsy. During migraine aura,
bursts of spike activity may appear similar to ictal EEG. However,
in most reported cases the EEG does not show the usual
evolution temporally with progressive increase and declines in
the frequency and amplitude of rhythmic, repetitive epiliptiform activity typical of ictal EEGs in epilepsy. A migraine attack can
originate at either a cortical or subcortical level, whilst epilepsy
generally arises cortically and can only be sub modulated at the
IEH is associated with other epileptic manifestations such as
ictal-sensory and motor features more frequently than literature
suggest. Therefore, an ictal EEG is recommended during a
migraine attack even in patients not known to suffer from
epilepsy, despite the fact that it is not always possible to detect
an ictal epileptic manifestation only by scalp EEG recording.
More research is required in this area and ictal EEG to become
more readily available.
Due to diagnostic uncertainty the existence of migralepsy
has been questioned often. The lack of published data highlights
the inadequacy of the current definitions of ICHD-II about
temporal and/or clinical link and overlap between migraine and
epilepsy . The concept of migralepsy in accordance to current
definitions is too narrow and inadequate and needs revision. It
has been suggested migralepsy could often be a simple seizure
starting with an ictal epileptic headache followed by a sensorymotor
partial or generalized seizure [3,20]. On the contrary there
is suggestion that headaches may be the sole representation of
an epileptic seizure [2,25,27,28].