A review of the genetic relation between migraine and epilepsy
J Haan,
GM Terwindt,
AMJM Van Den Maagdenberg,
AH Stam,
MD Ferrari,
Corresponding Author
J Haan
Department of Neurology, Leiden University Medical Centre,
Department of Neurology, Rijnland Hospital Leiderdorp and
Dr Joost Haan, MD, PhD, Department of Neurology K5Q, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, the Netherlands. Tel. + 31 7 1526 9111, e-mail [email protected]Search for more papers by this authorGM Terwindt
Department of Neurology, Leiden University Medical Centre,
Search for more papers by this authorAMJM Van Den Maagdenberg
Department of Neurology, Leiden University Medical Centre,
Department of Human Genetics, Leiden University Medical Centre, Leiden, the Netherlands
Search for more papers by this authorAH Stam
Department of Neurology, Leiden University Medical Centre,
Search for more papers by this authorMD Ferrari
Department of Neurology, Leiden University Medical Centre,
Search for more papers by this authorJ Haan,
GM Terwindt,
AMJM Van Den Maagdenberg,
AH Stam,
MD Ferrari,
Corresponding Author
J Haan
Department of Neurology, Leiden University Medical Centre,
Department of Neurology, Rijnland Hospital Leiderdorp and
Dr Joost Haan, MD, PhD, Department of Neurology K5Q, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, the Netherlands. Tel. + 31 7 1526 9111, e-mail [email protected]Search for more papers by this authorGM Terwindt
Department of Neurology, Leiden University Medical Centre,
Search for more papers by this authorAMJM Van Den Maagdenberg
Department of Neurology, Leiden University Medical Centre,
Department of Human Genetics, Leiden University Medical Centre, Leiden, the Netherlands
Search for more papers by this authorAH Stam
Department of Neurology, Leiden University Medical Centre,
Search for more papers by this authorMD Ferrari
Department of Neurology, Leiden University Medical Centre,
Search for more papers by this authorAbstract
A possible relation between migraine and epilepsy has been a matter of debate for many decades. Clinical, epidemiological and therapeutic similarities may be coincidental and are no proof of a common aetiological background. However, a genetically determined dysfunction of ion channels seems to point to a common underlying mechanism for both paroxysmal disorders. For example, mutations in the three known genes for familial hemiplegic migraine can cause epilepsy. It is likely that the development of specific drugs aimed at restoring ion-channel function and/or related cellular signalling pathways might benefit patients with epilepsy as well as those with migraine. This review will briefly summarize the clinical, epidemiological, pathophysiological and therapeutic similarities between migraine and epilepsy. Most attention will be paid to the genetic relationship between these two paroxysmal disorders.
References
- 1 Bazil CW. Migraine and epilepsy. Neurol Clin 1994; 12: 115–28.
- 2 Bigal ME, Lipton RB, Cohen J, Silberstein SD. Epilepsy and migraine. Epilepsy Behav 2003; 4 (Suppl. 2): S13–24.
- 3 Welch KMA, Lewis D. Migraine and epilepsy. In: NT Mathew, editor. Neurologic clinics. Advances in headache. Philadelphia, PA: W.B. Saunders Co., 1997: 107–15.
- 4 Haut SR, Bigal ME, Lipton RB. Chronic disorders with episodic manifestations: focus on epilepsy and migraine. Lancet Neurol 2006; 5: 148–57.
- 5 Bruyn GW. Migraine and epilepsy. Funct Neurol 1986; 1: 315–31.
- 6 Schon F, Blau JN. Post-epileptic headache and migraine. J Neurol Neurosurg Psychiatry 1987; 50: 1148–52.
- 7 Laplante P, Saint-Hilaire JM, Bouvier G. Headache as an epileptic manifestation. Neurology 1983; 33: 1493–5.
- 8 Young GB, Blume WT. Painful epileptic seizures. Brain 1983; 106: 537–54.
- 9 Ito M, Adachi N, Nakamura F, Koyama T, Okamura T, Kato M et al. Characteristics of postictal headache in patients with partial epilepsy. Cephalalgia 2004; 24: 23–8.
- 10 Yankovsky AE, Andermann F, Bernasconi A. Characteristics of headache associated with intractable partial epilepsy. Epilepsia 2005; 46: 1241–5.
- 11 Yankovsky AE, Andermann F, Mercho S, Dubeau F, Bernasconi A. Preictal headache in partial epilepsy. Neurology 2005; 65: 1979–81.
- 12
Lees F,
Watkins SM.
Loss of consciousness in migraine.
Lancet
1963; 186: 647–9.
10.1016/S0140-6736(63)90449-5 Google Scholar
- 13 Bickerstaff ER. The basilar artery and the migraine epilepsy syndrome. Proc R Soc Med 1962; 55: 167–9.
- 14 Haan J, Sluis P, Sluis LH, Ferrari MD. Acetazolamide treatment for migraine aura status. Neurology 2000; 55: 1588–9.
- 15 Hockaday JM, Whitty CW. Factors determining the electroencephalogram in migraine: a study of 560 patients, according to clinical type of migraine. Brain 1969; 92: 769–88.
- 16 Kinast M, Lueders H, Rothner AD, Erenberg G. Benign focal epileptiform discharges in childhood migraine (BFEDC). Neurology 1982; 32: 1309–11.
- 17 Sand T. Electroencephalography in migraine: a review with focus on quantitative electroencephalography and the migraine vs. epilepsy relationship. Cephalalgia 2003; 23 (Suppl. 1): 5–11.
- 18 Haan J, Ferrari MD, Brouwer OF. Acute confusional migraine. Case report and review of literature. Clin Neurol Neurosurg 1988; 90: 275–8.
- 19 Evans RW, Gladstein J. Confusional migraine or photoepilepsy? Headache 2003; 43: 506–8.
- 20 Ehrenberg BL. Unusual clinical manifestations of migraine and ‘the borderland of epilepsy’—reexplored. Semin Neurol 1991; 11: 118–27.
- 21 Marks DA, Ehrenberg BL. Migraine-related seizures in adults with epilepsy, with EEG correlation. Neurology 1993; 43: 2476–83.
- 22 Milligan TA, Bromfield E. A case of ‘migralepsy’. Epilepsia 2005; 46 (Suppl. 10): 2–6.
- 23 Velioglu SK, Ozmenoglu M. Migraine-related seizures in an epileptic population. Cephalalgia 1999; 19: 797–801.
- 24 Friedenberg S, Dodick DW. Migraine-associated seizure: a case of reversible MRI abnormalities and persistent nondominant hemisphere syndrome. Headache 2000; 40: 487–90.
- 25 Mateo I, Foncea N, Vicente I, Gomez BM, Garcia-Monco JC. Migraine-associated seizures with recurrent and reversible magnetic resonance imaging abnormalities. Headache 2004; 44: 265–70.
- 26 De Romanis F, Buzzi MG, Cerbo R, Feliciani M, Assenza S, Agnoli A. Migraine and epilepsy with infantile onset and electroencephalographic findings of occipital spike-wave complexes. Headache 1991; 31: 378–83.
- 27 Andermann F, Zifkin B. The benign occipital epilepsies of childhood: an overview of the idiopathic syndromes and of the relationship to migraine. Epilepsia 1998; 39 (Suppl. 4): S9–23.
- 28 Panayiotopoulos CP. Visual phenomena and headache in occipital epilepsy: a review, a systematic study and differentiation from migraine. Epileptic Disord 1999; 1: 205–16.
- 29 Walker MC, Smith SJM, Sisodiya SM, Shorvon SD. Case of simple partial status epilepticus in occipital lobe epilepsy misdiagnosed as migraine: clinical, electrophysiological, and magnetic resonance imaging characteristics. Epilepsia 2006; 1995: 1233–6.
- 30 Giroud M, Couillault G, Arnould S, Dauvergne M, Dumas R, Nivelon JL. Epilepsy with rolandic paroxysms and migraine, a non–fortuitous association. Results of a controlled study. Pediatrie 1989; 44: 659–64.
- 31 Wirrell EC, Hamiwka LD. Do children with benign rolandic epilepsy have a higher prevalence of migraine than those with other partial epilepsies or nonepilepsy controls? Epilepsia 2006; 47: 1674–81.
- 32 Saka E, Saygi S. Familial adult onset myoclonic epilepsy associated with migraine. Seizure 2000; 9: 344–6.
- 33 Baier WK, Doose H. Petit mal-absences of childhood onset: familial prevalences of migraine and seizures. Neuropediatrics 1985; 16: 80–3.
- 34 Hart YM, Andermann F. Migraine aura, seizures, and temporal lobe epilepsy. Adv Neurol 1999; 81: 145–52.
- 35 Petzold GC, Klingebiel R, Einhaupl KM, Arnold G, Valdueza JM, Dreier JP. Migraine-induced stroke in a patient with migraine-related epilepsy. Headache 2003; 43: 694–6.
- 36 Ottman R, Lipton RB. Comorbidity of migraine and epilepsy. Neurology 1994; 44: 2105–10.
- 37 Kupersmith MJ, Vargas ME, Yashar A, Madrid M, Nelson K, Seton A et al. Occipital arteriovenous malformations: visual disturbances and presentation. Neurology 1996; 46: 953–7.
- 38 Finsterer J. Central nervous system manifestations of mitochondrial disorders. Acta Neurol Scand 2006; 114: 217–38.
- 39 Kossoff EH, Hatfield LA, Ball KL, Comi AM. Comorbidity of epilepsy and headache in patients with Sturge–Weber syndrome. J Child Neurol 2005; 20: 678–82.
- 40 Matias-Guiu J, Galiano L, Vioque J, Falip R, Martin R. A case–control study to evaluate the association of epilepsy and migraine. Neuroepidemiology 1992; 11: 313–14.
- 41 Lipton RB, Ottman R, Ehrenberg BL, Hauser WA. Comorbidity of migraine: the connection between migraine and epilepsy. Neurology 1994; 44 (10 Suppl. 7): S28–32.
- 42 Tellez-Zenteno JF, Matijevic S, Wiebe S. Somatic comorbidity of epilepsy in the general population in Canada. Epilepsia 2005; 46: 1955–62.
- 43 Yamane LE, Montenegro MA, Guerreiro MM. Comorbidity headache and epilepsy in childhood. Neuropediatrics 2004; 35: 99–102.
- 44 Ludvigsson P, Hesdorffer D, Olafsson E, Kjartansson O, Hauser WA. Migraine with aura is a risk factor for unprovoked seizures in children. Ann Neurol 2006; 59: 210–13.
- 45 Steinlein OK. Genes and mutations in human idiopathic epilepsy. Brain Dev 2004; 26: 213–18.
- 46 Steinlein OK. Genetic mechanisms that underlie epilepsy. Nat Rev Neurosci 2004; 5: 400–8.
- 47 Steinlein OK. Nicotinic receptor mutations in human epilepsy. Prog Brain Res 2004; 145: 275–85.
- 48 Pietrobon D. Migraine: new molecular mechanisms. Neuroscientist 2005; 11: 373–86.
- 49 Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders, 2nd edn. Cephalalgia 2004; 24 (Suppl. 1): 1–160.
- 50 Ophoff RA, Terwindt GM, Vergouwe MN, Van Eijk R, Oefner PJ, Hoffman SMG et al. Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4. Cell 1996; 87: 543–52.
- 51 Jouvenceau A, Eunson LH, Spauschus A, Ramesh V, Zuberi SM, Kullmann DM et al. Human epilepsy associated with dysfunction of the brain P/Q-type calcium channel. Lancet 2001; 358: 801–7.
- 52 Holtmann M, Opp J, Tokarzewski M, Korn-Merker E. Human epilepsy, episodic ataxia type 2, and migraine. Lancet 2002; 359: 170–1.
- 53 Kors EE, Melberg A, Vanmolkot KR, Kumlien E, Haan J, Raininko R et al. Childhood epilepsy, familial hemiplegic migraine, cerebellar ataxia, and a new CACNA1A mutation. Neurology 2004; 63: 1136–7.
- 54 Beauvais K, Cave-Riant F, De Barace C, Tardieu M, Tournier-Lasserve E, Furby A. New CACNA1A gene mutation in a case of familial hemiplegic migraine with status epilepticus. Eur Neurol 2004; 52: 58–61.
- 55 Imbrici P, Jaffe SL, Eunson LH, Davies NP, Herd C, Robertson R et al. Dysfunction of the brain calcium channel CaV2.1 in absence epilepsy and episodic ataxia. Brain 2004; 127: 2682–92.
- 56 Vahedi K, Denier C, Ducros A, Bousson V, Levy C, Chabriat H et al. CACNA1A gene de novo mutation causing hemiplegic migraine, coma, and cerebellar atrophy. Neurology 2000; 55: 1040–2.
- 57 Kors EE, Haan J, Giffin NJ, Pazdera L, Schnittger C, Lennox GG et al. Expanding the phenotypic spectrum of the CACNA1A gene T666M mutation: a description of 5 families with familial hemiplegic migraine. Arch Neurol 2003; 60: 684–8.
- 58 Ducros A, Denier C, Joutel A, Cecillon M, Lescoat C, Vahedi K et al. The clinical spectrum of familial hemiplegic migraine associated with mutations in a neuronal calcium channel. N Engl J Med 2001; 345: 17–24.
- 59 Kors EE, Melberg A, Vanmolkot KRJ, Kumlien E, Haan J, Raininko R et al. Childhood epilepsy, familial hemiplegic migraine, cerebellar ataxia, and a new CACNA1A mutaton. Neurology 2004; 63: 1136–7.
- 60 Kors E, Terwindt GM, Vermeulen FLMG, Fitzsimons RB, Jardine PE, Heywood P et al. Delayed cerebral edema and fatal coma after minor head trauma: role of the CACNA1A calcium channel subunit gene and relationship with familial hemiplegic migraine. Ann Neurol 2001; 49: 753–60.
- 61 Curtain RP, Smith RL, Ovcaric M, Griffiths LR. Minor head trauma-induced sporadic hemiplegic migraine coma. Ped Neurol 2006; 34: 329–32.
- 62 Zhuchenko O, Bailey J, Bonnen P, Ashizawa T, Stockton DW, Amos C et al. Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha 1A-voltage-dependent calcium channel. Nat Genet 1997; 15: 62–9.
- 63 Sinke RJ, Ippel EF, Diepstraten CM, Beemer FA, Wokke JH, Van Hilten BJ et al. Clinical and molecular correlations in spinocerebellar ataxia type 6: a study of 24 Dutch families. Arch Neurol 2001; 58: 1839–44.
- 64 Jen J, Kim GW, Baloh RW. Clinical spectrum of episodic ataxia type 2. Neurology 2004; 62: 17–22.
- 65 Imbrici P, Jaffe SL, Eunson LH, Davier NP, Herd C, Robertson R et al. Dysfunction of the brain calcium Channel CaV2.1 in absence epilepsy and episodic ataxia. Brain 2004; 127: 2682–92.
- 66 Strupp M, Kalla R, Dichgans M, Freilinger T, Glasauer S, Brandt T. Treatment of episodic ataxia type 2 with the potassium channel blocker 4-Aminopyridine. Neurology 2004; 62: 1623–5.
- 67 Chioza B, Wilkie H, Nashef L, Blower J, McCormick D, Sham P et al. Association between the α (1a) calcium channel gene CACNA1A and idiopathic generalized epilepsy. Neurology 2001; 56: 1245–6.
- 68 Chioza B, Nashef L, Asherson P, Makoff A. CACNA1A and P/Q-type calcium channels in epilepsy. Lancet 2002; 359: 258.
- 69 Chioza B, Osei-Lah A, Nashef L, Suarez-Merino B, Wilkie H, Sham P et al. Haplotype and linkage disequilibrium analysis to characterize a region in the calcium channel gene CACNA1A associated with idiopathic generalized epilepsy. Eur J Hum Genet 2002; 10: 857–64.
- 70 Sander T, Toliat MR, Heils A, Becker C, Nurnberg P. Failure to replicate an allelic association between an exon 8 polymorphism of the human α (1A) calcium channel gene and common syndromes of idiopathic generalized epilepsy. Epilepsy Res 2002; 49: 173–7.
- 71 Dove LS, Abbott LC, Griffith WH. Whole-cell and single-channel analysis of P-type calcium currents in cerebellar Purkinje cells of Leaner mutant mice. J Neurosci 1998; 18: 7687–99.
- 72 Lorenzon NM, Lutz CM, Frankel WN, Beam KG. Altered calcium channel currents in Purkinje cells of the neurological mutant mouse Leaner. J Neurosci 1998; 18: 4482–9.
- 73 Mori Y, Wakamori M, Oda S, Fletcher CF, Sekiguchi N, Mori E et al. Reduced voltage sensitivity of activation of P/Q-type Ca2+ channels is associated with the ataxic mouse mutation Rolling Nagoya (Tg (Rol)). J Neurosci 2000; 20: 5654–62.
- 74 Wakamori M, Yamazaki K, Matsunodaira H, Teramoto T, Tanaka I, Niidome T et al. Single Tottering mutations responsible for the neuropathic phenotype of the P-type calcium channel. J Biol Chem 1998; 273: 34857–67.
- 75 Ayata C, Shimizu-Sasamata M, Lo EH, Noebels J, Maskowitz MA. Impaired neurotransmitter release and elevated threshold for cortical spreading depression in mice with mutations in the Alpha1A Subunit of P/Q type calcium channels. Neuroscience 2000; 95: 639–45.
- 76 Van den Maagdenberg AM, Pietrobon D, Pizzorusso T, Kaja S, Broos LA, Cesetti T et al. A Cacna1a knockin migraine mouse model with increased susceptibility to cortical spreading depression. Neuron 2004; 41: 701–10.
- 77 De Fusco M, Marconi R, Silvestri L, Atorino L, Rampoldi L, Morgante L et al. Haploinsufficiency of ATP1A2 encoding the Na+/K+ pump α2 subunit associated with familial hemiplegic migraine type 2. Nat Genet 2003; 33: 192–6.
- 78 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: 360–6.
- 79 Riant F, De Fusco M, Aridon P, Ducros A, Ploton C, Marchelli F et al. ATP1A2 mutations in 11 families with familial hemiplegic migraine. Hum Mutat 2005; 26: 281.
- 80 Marconi R, De Fusco M, Aridon P, Plewnia K, Rossi M, Carapelli S et al. Familial hemiplegic migraine type 2 is linked to 0.9 Mb region on chromosome 1q23. Ann Neurol 2003; 53: 376–81.
- 81 Martinelli BF, Aridon P, Zara F, Guerrini R, Marini C, De Fusco M et al. No evidence of ATP1A2 involvement in 12 multiplex Italian families with benign familial infantile seizures. Neurosci Lett 2005; 388: 71–4.
- 82
Buono RJ,
Ferraro TN,
O'Connor MJ,
Sperling MR,
Abbey M,
Finanger E et al.
Lack of association between temporal lobe epilepsy and a novel polymorphism in the α2 subunit gene (ATP1A2) of the sodium potassium transporting ATPase.
Am J Med Genet
2000; 96: 79–83.
10.1002/(SICI)1096-8628(20000207)96:1<79::AID-AJMG16>3.0.CO;2-Z CAS PubMed Web of Science® Google Scholar
- 83 Lohoff FW, Ferraro TN, Sander T, Zhao H, Dahl JP, Berrettini WH et al. No association between common variations in the human α2 subunit gene (ATP1A2) of the sodium-potassium-transporting ATPase and idiopathic generalized epilepsy. Neurosci Lett 2005; 382: 33–8.
- 84 Spadaro M, Ursu S, Lehmann-Horn F, Veneziano L, Antonini G, Giunti P et al. A G301R Na (+) /K (+) -ATPase mutation causes familial hemiplegic migraine type 2 with cerebellar signs. Neurogenetics 2004; 5: 177–85.
- 85 Jurkat-Rott K, Freilinger T, Dreier JP, Herzog J, Göbel H, Petzold GC et al. Variability of familial hemiplegic migraine with novel A1A2 Na+/K+-ATPase variants. Neurology 2004; 62: 1857–61.
- 86 Vanmolkot KRJ, Stroink H, Koenderink JB, Kors EE, Van Den Heuvel JJ, Van Den Boogerd EH et al. Severe episodic neurological deficits and permanent mental retardation in a child with a novel FHM2 TP12 mutation. Ann Neurol 2006; 59: 310–14.
- 87 Swoboda KJ, Kanavakis E, Xaidara A, Johnson JE, Leppert MF, Schlesinger-Massart MB et al. Alternating hemiplegia of childhood or familial hemiplegic migraine? A novel ATP1A2 mutation. Ann Neurol 2004; 55: 884–7.
- 88 Ikeda K, Onaka T, Yamakado M, Nakai J, Ishikawa TO, Taketo MM et al. Degeneration of the amygdala/piriform cortex and enhanced fear/anxiety behaviors in sodium pump α2 subunit (Atp1a2)-deficient mice. J Neurosci 2003; 23: 4667–76.
- 89 James PF, Grupp IL, Grupp G, Woo AL, Askew GR, Croyle M et al. Identification of a specific role for the Na,K-ATPase α2 isoform as a regulator of calcium in the heart. Mol Cell 1999; 3: 555–63.
- 90 Dichgans M, Freilinger T, Eckstein G, Babini E, Lorenz-Depiereux B, Biskup S et al. Mutation in the neuronal voltage-gated sodium channel SCN1A in familial hemiplegic migraine. Lancet 2005; 366: 371–7.
- 91 Meisler MH, Kearney JA. Sodium channel mutations in epilepsy and other neurological disorders. J Clin Invest 2005; 115: 2010–17.
- 92 Yu FH, Mantegazza M, Westenbroek RE, Robbins CA, Kalume F, Burton KA et al. Reduced sodium current in GABAergic interneurons in a mouse model of severe myoclonic epilepsy in infancy. Nat Neurosci 2006; 9: 1142–9.
- 93 Hamberger A, Van Gelder NM. Metabolic manipulation of neural tissue to counter the hypersynchronous excitation of migraine and epilepsy. Neurochem Res 1993; 18: 503–9.
- 94 Johnson MP, Griffiths LR. A genetic analysis of serotonergic biosynthetic and metabolic enzymes in migraine using a DNA pooling approach. J Hum Genet 2005; 50: 607–10.
- 95 Theodore WH. Serotonin receptors: a new epilepsy imaging modality? Epilepsy Curr 2005; 5: 33–4.
- 96 Chen SC. Epilepsy and migraine: the dopamine hypotheses. Med Hypotheses 2006; 66: 466–72.
- 97 Chronicle E, Mulleners W. Anticonvulsant drugs for migraine prophylaxis. Cochrane Database Syst Rev 2004; 3: CD003226.
- 98 Kaczmarek LK. Non-conducting functions of voltage-gated ion channels. Nat Rev Neurosci 2006; 7: 761–71.
- 99 Ashcroft FM. From molecule to malady. Nature 2006; 440: 440–7.
- 100 Montagna P, Pierangeli G, Cevoli S, Mochi M, Cortelli P. Pharmacogenetics of headache treatment. Neurol Sci 2005; 26 (Suppl. 2): S143–7.
