Seizure 18 (2009) 309–312
Contents lists available at ScienceDirect
Seizure
journal homepage: www.elsevier.com/locate/yseiz
Review
Why is migraine rarely, and not usually, the sole ictal epileptic manifestation?
Pasquale Parisi *
Child Neurology and Pediatric Headache Centre, Department of Pediatrics, ‘‘La Sapienza’’ University, Viale Regina Elena 324, 00161 Rome, Italy
A R T I C L E I N F O
A B S T R A C T
Article history:
Received 14 September 2008
Received in revised form 8 November 2008
Accepted 16 January 2009
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 underdiagnosed 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.
ß 2009 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Keywords:
Migraine
Epilepsy
Hemicrania epileptica
Ictal epileptic headache
Cortical spreading depression
CSD
Trigemino-vascular theory
Contents
1.
2.
3.
4.
Links between CSD and the migraine trigemino-vascular theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Link between CSD and cortical focal paroxysmal discharge (neurophysiopathologic and genetic link level) . . . . . . . . . . . . . . . . . . . . . . . . .
Link between migraine and epilepsy (clinical link level) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Final hypothesis, suggestions and future directions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.1.
Why is migraine rarely, and not usually, the sole ictal epileptic phenomenon?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1. Links between CSD and the migraine trigemino-vascular
theory
Functional neuroimaging1 and neurophysiological studies2–7
have revealed that primary headaches (both tension-type and
migraine type) may be characterised by different activation
patterns of the central and peripheral pain modulatory structures,
most of which have been identified by numerous authors in recent
decades as possible sites of specific impairment (functional or
structural) involved in the physiopathology of headache.2–11
Among these, studies on the role of cortical spreading depression
(CSD) and trigemino-vascular system (TVS) activation in the
* Tel.: +39 06 49979311; fax: +39 06 49979312.
E-mail address: [email protected].
309
310
310
310
311
311
physiopathology of migraine have attracted the attention of the
leading experts in this field.12–13
The discovery of CSD represents a perfect example of so-called
‘‘serendipity phenomena’’. In other words, it illustrates how an
unexpected, chance observation, if made by an alert experimenter,
can open a new, major area of investigation.14–15 In animals, CSD can
be triggered by focal stimulation (electrical, mechanical, with high
extracellular K+ or glutamate, persistent intracellular sodium influx,
inhibition of the Na+–K+ ATPase pump), as well as by several other
stimuli of the cerebral cortex, more readily in the occipital region
than in other regions.14–16 CSD is characterized by a slowly
propagating wave (2–6 mm/min) of sustained strong neuronal
depolarization that generates transient (in the order of seconds),
intense spike activity as it progresses into the tissue, followed by
neural suppression which may last for minutes. CSD represents a
regenerative ‘‘all-or-none’’ event (a neurophysiologic characteristic
shared with the ‘‘membrane depolarization’’ underlying a focal
1059-1311/$ – see front matter ß 2009 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.seizure.2009.01.010
310
P. Parisi / Seizure 18 (2009) 309–312
epileptic discharge event) that propagates slowly in a wave-like
fashion in brain tissue. The depolarization phase is associated with
an increase in regional cerebral blood flow (rCBF), whereas the phase
of reduced neural activity is associated with a reduction in rCBF.
Opinions are divided as to whether CSD plays a physiological17 or a
neuro-protective role.18
Moskowitz and co-workers have, since 1993, been making a
major contribution, by means of experimental data12,13,19 and
functional neuroradiological investigations in humans,1 to the
search for possible correlations between CSD onset and TVS
activation; TVS activation is considered to represent ‘‘the common
final pathway’’, which consists of a cascade release of numerous
inflammatory molecules (sterile inflammation) and neurotransmitters that are a ‘‘sine qua non’’ condition resulting in pain during
the attacks. CSD is considered to be the primary cause for TVS
activation. These studies by Moskowitz and co-workers have
strongly contributed to the formulation of the ‘‘trigemino-vascular
theory’’, which has become the most widely accepted theory in the
physiopathology of migraine. The correlation between CSD and
migraine with aura (MA) was demonstrated first12,13,19; more
recently, imaging studies in patients suffering from migraine
without aura (MoA) have also pointed to the presence of CSD in
silent areas as an underlying mechanism.20–23
It should be borne in mind that CSD is not a phenomenon that is
‘‘strictly’’ peculiar to the cortical structures. Cortical and subcortical areas appear to be hierarchically divided according to how
likely they are to develop CSD,14,24 though the occipital lobe
appears to be the area most likely to be affected.
2. Link between CSD and cortical focal paroxysmal discharge
(neurophysiopathologic and genetic link level)
Worthy of attention is an old finding in the literature regarding
the properties and the critical role that the Na+–K+ ATPase pump
plays in the regulation of both seizure onset, by acting on
membrane depolarization (due to inhibitory potential postsynaptic modulation), and CSD, by modifying the local K+
concentration. This old experimental finding linked both seizure
and CSD onset to the ability of the Na–K pump to regulate K+
extracellular concentrations.25 Intriguingly, thirteen years later,
this experimental finding was confirmed in humans by a novel
mutation in the Na+–K+ ATPase pump associated with two
phenotypically different pictures: familial hemiplegic migraine
(FHM) and benign familial infantile convulsions (BFIC).26 Moreover, a monogenic defect in familial occipital lobe epilepsy
associated with MA was reported.27
An important role in the phenomenon linking the onset of CSD
and cortical focal epileptic discharges might be played by
complementary mechanisms responsible for ionic diffusion in
both these events (i.e. epileptic depolarization and CSD onset). The
velocity of ionic diffusion across neuronal cytoplasmic bridges (gap
junctions) is different from that through interstitial spaces, though
both converge in the membrane excitability modulation. Synchronization in CSD has been hypothesized to be caused by the nonsynaptic interaction between neurones mediated by the excitatory
neurotransmitter glutamate or through ‘‘gap junctional’’ interactions.28 Moreover, the previously reported gap junction properties
in the modulation of CSD onset29 and spreading14,29 as well as the
anticonvulsant properties of gap junction blockers30 have been
documented. Yet other data highlight the role of gap junctions in
synchronizing the human neocortical network, which in turn
increases epileptiform activity.31
More recently,32 CSD has been reported to facilitate synaptic
excitability in human neocortical tissues, thus contributing to the
hyperexcitability of neocortical tissues in patients suffering from
migraine. Moreover, calcium-sensitive current can promote both
seizure-like discharges and CSD in a model neuron.33 Data thus
confirm that CSD (migraine) and cortical focal discharges
(seizures) facilitate each other.
Lastly, it is highly interesting that these data are supported,
going back into the past, by Leao himself, who described, while
studying ‘‘experimental epilepsy’’,34 CSD onset due to the
propagation of electrically provoked seizure discharges in the
cerebral cortex and, in the same article, the similarity in the ways
in which CSD and seizures propagate.
3. Link between migraine and epilepsy (clinical link level)
The association between headache/migraine and seizures is a
widespread, well-known event. Headache/migraine are associated
with seizure occurrence in 34–58% of epileptic patients, 60% of
whom have a peri-ictal headache alone, i.e. headache/migraine in
such subjects are always temporally related to seizures. According
to the international criteria,35 about 37% of headaches are tensiontype while about 55% are migraine (75% MoA and 15% MA)36–39;
the rate of peri-ictal headache reported in the literature (34–58%)
is very similar in both past36 and more recent37–39 studies. The
temporal relationship between migraine/headache and seizures
allows us to subdivide headaches as follows36–39: 5–27% are only
pre-ictal, 2.2% are ictal,38 30–70% are only post-ictal, while 7–27%
are both pre-ictal and post-ictal.
Problems have arisen in international criteria regarding the
definition of the rare condition in which migraine (even more
rarely, tension-type headache) may be the sole semeiologic
manifestation of the epileptic seizure.
Our group recently described40 a 14-year-old girl who had a
photosensitive occipital epileptic seizure followed by a status
migrainosus that lasted 3 days. An EEG revealed occipital status
epilepticus during her migraine attack; intravenous administration of diazepam, under continuous EEG recording, suppressed
both the epileptiform discharges and headache complaints. Three
days later, we evoked visual aura and migraine in this patient
during an EEG recording by means of intermittent photic
stimulation (IPS).40 It is particularly intriguing that IPS can trigger
both migraine attacks and epileptic seizures. On the basis of our
observations, we also recently suggested that the diagnostic
criteria for ‘‘hemicrania epileptica’’ in Migraine and Epilepsy
International Classifications35,41 be revised, and that the importance of EEG recordings with standardized IPS be stressed.42,43 We
also proposed the term ‘‘ictal epileptic headache’’ for ‘‘migraine/
headache’’ as the sole semeiologic epileptic ictal phenomena.43
Another noteworthy point is the existence of migraine attacks
that occur separately in-between epileptic seizures (interictal
migraine), which may (rarely) represent the sole ictal epileptic
manifestation in subjects previously diagnosed as epileptic and
(even more rarely) in patients in whom epilepsy was not
diagnosed. In this regard, the role of EEG recording should not
be underestimated.
4. Final hypothesis, suggestions and future directions
The ‘‘sine qua non’’ condition for headache is TVS activation,
which is believed to be the only neural pathway able to induce
migraine (with or without aura).
In the central nervous system, there appears to be a hierarchical
organization based on ‘‘neuronal networks’’ (cortical and subcortical) that may be more or less prone to CSD (migraine) and
epileptic focal discharges (seizures). Onset and propagation are
triggered when these neurophysiological events reach a certain
threshold (‘‘all or-none events’’), which is lower for the onset of
CSD than that of the seizure. Once the cortical event is started, the
way in which it spreads depends on the size of the onset zone, its
P. Parisi / Seizure 18 (2009) 309–312
velocity, semeiology and type of propagation of the cortical event,
all of which may vary within the same patient at different times.
The onset of CSD and of the epileptic seizure may facilitate each
other.14,16,31,32 The underlying neurophysiological causes may be
the same, with the two phenomena displaying the ‘‘all-or-none’’
(as mentioned above) characteristic, which may be triggered by
more than one pathway converging upon the same destination
(depolarization and hypersynchronization). The triggering causes,
which may be environmental or individual (whether genetically
determined or not), result in a flow of ions that mediate CSD above
all through neuronal (and probably glial) cytoplasmic bridges
(intracellular gap-junctions) rather than through interstitial
spaces, as usually happens in the spreading of epileptic
seizures.14,44 Furthermore, the threshold required for the onset
of CSD is likely to be lower than that required for the epileptic
seizure. In other words, I believe that the onset of the epileptic
seizure facilitates the onset of CSD to a greater degree than the
onset of CSD facilitates the onset of the epileptic seizure. Thus, as
epidemiologic studies in the literature suggest,36–39,45,46 in the
clinical context we are more likely to observe epileptic patients
with ‘‘comorbid’’ (peri-ictal and interictal) migraine than migraine
subjects with ‘‘comorbid’’ epilepsy.
4.1. Why is migraine rarely, and not usually, the sole ictal epileptic
phenomenon?
Migraine without aura is thought to be the result of a CSD that
starts and propagates from silent cortical areas following TVS
activation (pain phase), without any additional signs/symptoms.
Similarly, an epileptic seizure, whose onset and propagation occur
along silent/non-eloquent cortical areas, may activate the TVS,
which results in a migraine attack without any additional epileptic
signs/symptoms.40,42–44 The latter condition is understandably
very rare, it being statistically highly unlikely that this type of
event might occur by chance. This observation is supported by the
fact that peri-ictal headaches associated with other signs/
symptoms during an epileptic seizure are very common (34–
58%),36–39,45,46 which in turn confirms that the threshold for
migraine onset is lower than that of seizure onset. In this regard, a
‘migraleptic’ event, i.e. a migraine attack followed by epileptic
seizures, is also very rare because the threshold required for
seizure onset and propagation is higher.
Therefore, migraine (with or without aura), along with all other
headache types (the literature on other headache disorders is
unfortunately more limited), is highly unlikely to be an epileptic
event, but rather the result of cortical or subcortical events that
activate the TVS. These events might consist of CSD or ‘‘subcortical’’
spreading depression, or be caused by environmental, individual or
genetic noxae, which cause an impairment that ‘‘interferes’’ with
the very complex polysynaptic and polymolecular cascade at the
subcortical level in the TVS networks.
The last, though not the least, of the considerations that arise
from this hypothesis concerns the under-diagnosed ictal epileptic
headache which, while rare, is a strongly debated topic that
deserves some considerations. Indeed, the potential implications
that arise from this topic include44: (a) a revision of the headache/
migraine diagnostic criteria in order to include headache/migraine
criterion as a possible sole ictal epileptic manifestation42; (b) the
careful follow-up of patients with headache/migraine as a residual
feature, taking into account a revised concept of ‘‘complete seizure
control’’ to avoid mistakes due to the inopportune withdrawal of
antiepileptic treatment.42,44 In addition, it should be borne in mind
that headache may be associated with ictal-sensory and motor
features more frequently than the literature suggests; indeed, this
association might be strongly underestimated owing to impaired
consciousness during complex partial seizures with or without
311
secondary generalization. In this respect, an ictal EEG (during the
migraine attack) should be recommended in every migraine
patient, even in subjects who are not known to be epileptic. During
an interictal EEG (or video-EEG) recording, particular attention
should always be paid to the ictal onset of the clinical-EEG findings
(and not the EEG abnormalities alone, which are relatively
common) during IPS, performed according to the standardized
international protocol.47 As regards the criteria for the selection of
patients in whom a more thorough EEG investigation is warranted,
the abrupt onset of headache, a short attack duration (i.e. lasting
minutes) and the migraine-like characteristics of the attacks (as
opposed to the tension-type ones) may be a good starting point.
Another intriguing issue is the difference between the clinical
picture of adult and that of childhood in both epilepsy and
headache. Autonomic manifestations are more prevalent in the
childhood headache clinical picture, as well it is observed in most
early benign focal idiopathic epileptic childhood syndromes, such
as the well-known Panayiotopoulos syndrome (PS). In this regard,
our group documented a child affected by PS48 whose interictal
migraine attacks (in-between the nocturnal seizures) completely
remitted (as did the seizures) after the administration of anticonvulsant therapy.
From the therapeutic point of view, the anticipation of the
cortical event (CSD) that induces secondary TVS activation
probably explains why AED treatment is more effective in the
prophylaxis phase than in the pain phase (migraine attack). In
order to ‘‘interfere’’ with this very complex polysynaptic and
polymolecular cascade, several cortical and subcortical levels must
be acted upon; the model proposed here (multiple different
cortical and subcortical levels underlying the onset of migraine
attacks) is supported in the literature by a number of molecules
with different pharmacological properties that have proved
(clinically and experimentally)8,19,49–55 to play a therapeutic role
in migraine.
Future research is warranted to identify the various levels of the
cortico-subcortical polysynaptic molecular cascade, which will
hopefully provide migraine (whether epileptic or not) therapy with
specific pharmacological properties tailored for individual
patients.
Conflict of interest
I have no conflict of interest in publishing this article.
References
1. Hadjikhani N, Sanchez del Rio M, Wu O, Schwartz D, Bakker D, Fischl B, et al.
Mechanisms of migraine aura revealed by functional MRI in human visual
cortex. PNAS 2001;98(8):4687–92.
2. Valeriani M, Rinalduzzi S, Vigevano F. Multilevel somatosensory system disinhibition in children with migraine. Pain 2005;118(1–2):137–44.
3. Olsson T, Broberg M, Pope KJ, Wallace A, Mackenzie L, Blomstrand F, et al. Cell
swelling, seizures and spreading depression: an impedance study. Neuroscience
2006;140:505–15.
4. de Tommaso M, Lo sito L, Di fruscolo O, Sardaro M, Pia Prudenzano M, Lamberti
P, et al. Lack of habituation of nociceptive evoked responses and pain sensitivity
during migraine attack. Clin Neurophysiol 2005;116:1254–64.
5. Sandrini G, Rossi P, Milanov I, Serrao M, Cecchini AP, Nappi G. Abnormal
modulatory influence of diffuse noxious inhibitory controls in migraine and
chronic tension-type headache patients. Cephalalgia 2006;26:782–9.
6. Magis D, Ambrosini A, Bendtsen L, Ertas M, Kaube H, Schoenen J. Evaluation and
proposal for optimalization of neurophysiological tests in migraine: Part 1—
electrophysiological tests. Cephalalgia 2007;27:1323–38.
7. Magis D, Bendtsen L, Goadsby PJ, May A, Sánchez del Rio M, Sandór PS, et al.
Evaluation and proposal for opimization of neurophysiological tests in
migraine: Part 2—neuroimaging and the nitroglycerin test. Cephalalgia
2007;27:1339–59.
8. Storer RJ, Akerman S, Goadsby PJ. Calcitonin gene-related peptide (CGRP)
modulates nociceptive trigeminovascular transmission in the cat. British Journal
of Pharmacology 2004;142:1171–81.
9. Knight YE, Goadsby PJ. The periacqueductal grey matter modulates trigeminovascular input: a role in migraine? Neuroscience 2001;106(4):793–800.
312
P. Parisi / Seizure 18 (2009) 309–312
10. Peres MF, Sanchez del Rio M, Seabra ML, Tufik S, Abucham J, Cipolla-Neto J, et al.
Hypothalamic involvement in chronic migraine. J Neurol Neurosurg Psychiatr
2001;71:745–51.
11. Holland PR, Akerman S, Goadsby PJ. Orexin 1 receptor activation attenuates
neurogenic dural vasodilation in an animal model of trigeminovascular nociception. J Pharmacol Exp Ther 2005;315(3):1380–5.
12. Moskowitz MA, Nozaki K, Kraig RP. Neocortical spreading depression provokes
the expression of C-fos protein-like lmmunoreactivity within trigeminal
nucleus caudalis via trigeminovascular mechanisms. J Neurosci 1993;13(3):
1167–77.
13. Bolay H, Reuter U, Dunn AK, Huang Z, Boas DA, Moskowitz MA. Intrinsic brain
activity triggers trigeminal meningeal afferents in a migraine model. Nat Med
2002;8(2):136–42.
14. Somjen GG. Mechanisms of spreading depression and hypoxic spreading
depression-like depolarization. Physiol Rev 2001;81(3):1065–96.
15. Somjen GG. Aristides Leão’s discovery of cortical spreading depression. J
Neurophysiol 2005;94:2–4.
16. Somjen GG. Is spreading depression bad for you? Focus on ‘‘Repetitive normoxic
spreading depression-like events result in cell damage in juvenile hippocampal
slice cultures’’ J Neurophysiol 2006;95:16–7.
17. Bures J, Buresova O, Krivanek O. The meaning and significance of Leao’s
spreading depression. An Acad Bras Cienc 1984;56:385–400.
18. Kunkler PE, Hulse RE, Kraig RP. Multiplexed cytokine protein expression
profiles from spreading depression in hippocampal organotypic cultures. J
Cereb Blood Flow Metab 2004;24:829–39.
19. Ayata C, Jin H, Kudo C, Dalkara T, Moskowitz MA. Suppression of cortical
spreading depression in migraine prophylaxis. Ann Neurol 2006;59(4):652–61.
20. Woods RP, Iacoboni M, Mazziotta JC. Bilateral spreading cerebral hypoperfusion
during spontaneous migraine headache. N Engl J Med 1994;331:1689–92.
21. Géraud G, Denuelle M, Fabre N, Payoux P, Chollet F. Positron emission studies in
migraine. Rev Neurol (Paris) 2005;161:666–70.
22. Chalaupka FD. Reversible imaging abnormalities consistent with CSD during
migraine without aura attack. Headache 2008;48(8):1229–32.
23. Purdy RA. Migraine with and without aura share the same pathogenic mechanisms. Neurol Sci 2008;29:S44–6.
24. Richter F, Bauer R, Lehmenkuhler A, Schaible HG. Spreading depression in the
brainstem of the rat: electrophysiological parameters and influences on regional brainstem blood flow. J Cereb Blood Flow Metab 2008;28:984–94.
25. Haglund MM, Schwartzkroin PA. Role of Na-K pump potassium regulation and
IPSPs in seizures and spreading depression in immature rabbit hippocampal
slices. J Neurophysiol 1990;63(2):225–39.
26. Vanmolkot KR, Kors EE, Hottenga JJ, Terwindt GM, Haan J, Hoefnagels WA, et al.
Novel mutations in the Na+, K+-ATPase pump gene ATP1A2 associated with
familial hemiplegic migraine and benign familial infantile convulsions. Ann
Neurol 2003;54(3):360–6.
27. Deprez L, Peeters K, Van Paesschen W, Claeys KG, Claes LR, Suls A, et al. Familial
occipitotemporal lobe epilepsy and migraine with visual aura. Linkage to
chromosome 9q. Neurology 2007;68:1995–2002.
28. Larrosa B, Pastor J, Lopez-Aguado L, Herreras O. A role for glutamate and glia in
the fast network oscillations precedine spreading depression. Neuroscience
2006;141:1057–68.
29. Nedergaard M, Cooper AJ, Goldman SA. Gap junctions are required for the
propagation of spreading depression. J Neurobiol 1995;28(4):433–44.
30. Nilsen KE, Andrew R, Kelso C, Cock HR. Antiepileptic effect of gap-junction
blockers in a rat model of refractory focal cortical epilepsy. Epilepsia
2006;47(7): 1169–75.
31. Gigout S, Louvel J, Kawasaki H, D’Antuono M, Armand V, Kurcewicz I, et al.
Effects of gap junction blockers on human neocortical synchronization. Neurobiol Dis 2006;22(3):496–508.
32. Berger M, Speckmann EJ, Pape HC, Gorji A. Spreading depression enhances
human neocortical excitability in vitro. Cephalalgia 2008;28:558–62.
33. Somjen GG, Kager H, Wadman WJ. Calcium sensitive non-selective cation
current promotes seizure-like discharges and spreading depression in a model
neuron. J Comput Neurosci; in press. doi:10.1007/s10827-008-0103-9.
34. Leao AAP. Spreading depression of activity in the cerebral cortex. J Neurophysiol
1944;7:359–90.
35. Headache Classification Subcommittee of The International Headache Society.
The international classification of headache disorders, 2nd ed. Cephalalgia
2004;24(Suppl.):1–160.
36. Schon F, Blau JN. Post-epileptic headache and migraine. J Neurol Neurosurg
Psychiatr 1987;50:1148–52.
37. Leniger T, Isbruch K, von den Driesch S, Diener HC, Hufnagel A. Seizureassociated headache in epilepsy. Epilepsia 2001;42(9):1176–9.
38. Karaali-Savrun F, Goksan B, Naz Yeni S, Ertan S, Uzun N. Seizure-related
headache in patients with epilepsy. Seizure 2002;11:67–9.
39. Cai S, Hamiwka LD, Wirrell EC. Peri-ictal headache in children: prevalence and
character. Pediatr Neurol 2008;39:91–6.
40. Parisi P, Kasteleijn-Nolst Trenite DGA, Piccioli M, Pelliccia A, Luchetti A, Buttinelli C, et al. A case with atypical childhood occipital epilepsy ‘‘Gastaut type’’:
an ictal migraine manifestation with a good response to intra-venous diazepam. Epilepsia 2007;48(11):2181–6.
41. Proposal for revised classification of epilepsies and epileptic syndromes. Commission on Classification and Terminology of the International League Against
Epilepsy. Epilepsia 1989;30(4):389–99.
42. Parisi P, Piccioli M, de Sneeuw S, de Kovel C, van Nieuwenhuizen O, Buttinelli C,
et al. Redefining headache diagnostic criteria as epileptic manifestation?
Cephalalgia 2008;28:408–9.
43. Piccioli M, Parisi P, Tisei P, Villa MP, Buttinelli C, Kasteleijn-Nolst Trenité DGA.
Ictal headache and visual sensitivity. Cephalalgia 2008. 10.1111/j.14682982.2008.01707.x. [published online September 24].
44. Parisi P, Piccioli M, Villa MP, Buttinelli C, Kasteleijn-Nolst Trenate DGA.
Hypothesis on neurophysiopathological mechanisms linking epilepsy and
headache. Med Hypotheses 2008;70:1150–4.
45. Ottman R, Lipton RB. Comorbidity of migraine and epilepsy. Neurology
1994;44(11):2105–10.
46. Lipton RB, Ottman R, Ehremberg BL, Hauser WA. Comorbidity of migraine: the
connection between migraine and epilepsy. Neurology 1994;44(10 Suppl 7):S28–
32.
47. Kasteleijn-Nolst Trenate DG, Zinnie CD, Harding GF. Photic stimulation: standardization of screening methods. Epilepsia 1999;40(Suppl. 4):75–9. [Review].
48. Parisi P, Ferri R, Pagani J, Montemitro E, Cecili M, Villa MP. Ictal video-polysomnography and EEG spectral analysis in a child with severe panayiotopoulos
syndrome. Epileptic Disord 2005;7(4):333–9.
49. Mulleners WM, Chronicle EP. Anticonvulsants in migraine prophylaxis: a
Cochran review. Cephalalgia 2008;28:585–97.
50. Knight YE, Bartsch T, Kaube H, Goadsby PJ. P/Q-type calcium-channel blockade
in the periaqueductal gray facilitates trigeminal nociception: a functional
genetic link for migraine? J Neurosci 2002;22:1–6. [RC213].
51. Bussone G, Diener H-C, Pfeil J, Schwalen S. Topiramate 100 mg/day in migraine
prevention: a pooled analysis of double-blinded randomised controlled trials.
Int J Clin Pract 2005;59:961–8.
52. Ben-Menachem E, Sander JW, Stefan H, Schwalen S, Schauble B. Topiramate
monotherapy in the treatment of newly or recently diagnosed epilepsy. Clin
Ther 2008;30:1180–95.
53. Pascual J, Mateos V, Roig C, Sanchez del Rio M, Jimenéz D. Marketed oral triptans
in the acute treatment of migraine: a systematic review on efficacy and
tolerability. Headache 2007;47(8):1152–68.
54. Arulmozhi DK, Veeranjaneyulu A, Bodhankar SL. Migraine: current therapeutic
targets and future avenues. Curr Vasc Pharmacol 2006;4(2):117–28.
55. Akerman S, Holland PR, Goadsby PJ. Mechanically-induced cortical spreading
depression associated regional cerebral blood flow changes are blocked by
Na(+) ion channel blockade. Brain Res 2008;1229:27–36.