Headache and Epilepsy

  • P. R. Bauer
  • J. A. Carpay
  • G. M. Terwindt
  • J. W. Sander
  • R. J. Thijs
  • J. Haan
  • G. H. Visser
Secondary Headache (K Henry, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Secondary Headache

Abstract

Headache and epilepsy often co-occur. Epidemiologic studies conducted in the past few years reinforce the notion of a bi-directional association between migraine and epilepsy. Data on an association between headache (in general) and epilepsy, however, are less clear. Peri-ictal headache often presents with migraine-like symptoms and can be severe. A correct diagnosis and management are paramount. It was demonstrated that cortical hyperexcitability may underlie both epilepsy and migraine. A recent study linked spreading depolarisation, the supposed underlying pathophysiological mechanism of migraine with aura, to epilepsy. Although this study was carried out in patients who had suffered a subarachnoid haemorrhage, the finding may shed light on pathophysiological mechanisms common to epilepsy and migraine.

Keywords

Headache Migraine Epilepsy Post-ictal headache Peri-ictal headache Migralepsy Ictal headache Cortical excitability Familial hemiplegic migraine Cortical spreading depression Cortical spreading depolarisation 

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Stovner L, Hagen K, Jensen R, et al. The global burden of headache: a documentation of headache prevalence and disability worldwide. Cephalalgia. 2007;27(3):193–210.PubMedCrossRefGoogle Scholar
  2. 2.
    Smitherman TA, Burch R, Sheikh H, Loder E. The prevalence, impact, and treatment of migraine and severe headaches in the United States: a review of statistics from national surveillance studies. Headache. 2013. doi:10.111/head.12074.Google Scholar
  3. 3.
    MacDonald BK, Cockerell OC, Sander JW, Shorvon SD. The incidence and lifetime prevalence of neurological disorders in a prospective community-based study in the UK. Brain. 2000;123:665–76.PubMedCrossRefGoogle Scholar
  4. 4.
    Forsgren L, Beghi E, Oun A, Sillanpää M. The epidemiology of epilepsy in Europe - a systematic review. Eur J Neurol. 2005;12(4):245–53.PubMedCrossRefGoogle Scholar
  5. 5.
    Sander JW. The epidemiology of epilepsy revisited. Curr Opin Neurol. 2003;16(2):165–70.PubMedCrossRefGoogle Scholar
  6. 6.
    Kwan P, Man CBL, Leung H, et al. Headache in patients with epilepsy: a prospective incidence study. Epilepsia. 2008;49(6):1099–102.PubMedCrossRefGoogle Scholar
  7. 7.
    Syvertsen M, Helde G, Stovner LJ, Brodtkorb E. Headaches add to the burden of epilepsy. J Headache Pain. 2007;8(4):224–30.PubMedCrossRefGoogle Scholar
  8. 8.
    Ito M, Adachi N, Nakamura F, et al. Characteristics of postictal headache in patients with partial epilepsy. Cephalalgia. 2004;24(1):23–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Nunes JC, Zakon DB, Claudino LS, et al. Headache among mesial temporal lobe epilepsy patients: a case-control study. J Neurol Sci. 2011;306(1-2):20–3.PubMedCrossRefGoogle Scholar
  10. 10.
    Yankovsky AE, Andermann F, Bernasconi A. Characteristics of headache associated with intractable partial epilepsy. Epilepsia. 2005;46(8):1241–5.PubMedCrossRefGoogle Scholar
  11. 11.
    Ottman R, Lipton RB, Ettinger AB, et al. Comorbidities of epilepsy: results from the Epilepsy Comorbidities and Health (EPIC) survey. Epilepsia. 2011;52(2):308–15.PubMedGoogle Scholar
  12. 12.
    Téllez-Zenteno JF, Matijevic S, Wiebe S. Somatic comorbidity of epilepsy in the general population in Canada. Epilepsia. 2005;46(12):1955–62.PubMedCrossRefGoogle Scholar
  13. 13.
    Le H, Tfelt-Hansen P, Russell MB, et al. Co-morbidity of migraine with somatic disease in a large population-based study. Cephalalgia. 2011;31(1):43–64.PubMedCrossRefGoogle Scholar
  14. 14.
    Brodtkorb E, Bakken IJ, Sjaastad O. Comorbidity of migraine and epilepsy in a Norwegian community. Eur J Neurol. 2008;15(12):1421–3.PubMedCrossRefGoogle Scholar
  15. 15.
    Buse DC, Manack A, Serrano D, Turkel C, Lipton RB. Sociodemographic and comorbidity profiles of chronic migraine and episodic migraine sufferers. J Neurol Neurosurg Psychiatry. 2010;81(4):428–32.PubMedCrossRefGoogle Scholar
  16. 16.
    Chen Y-C, Tang C-H, Ng K, Wang S-J. Comorbidity profiles of chronic migraine sufferers in a national database in Taiwan. J Headache Pain. 2012;13(4):311–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Lateef TM, Cui L, Nelson KB, et al. Physical comorbidity of migraine and other headaches in US adolescents. J Pediatr. 2012;161(2):308–13.PubMedCrossRefGoogle Scholar
  18. 18.
    Olesen J. The international classification of headache disorders. Headache. 2004;24(s1):1–150.Google Scholar
  19. 19.
    Kelley SA, Hartman AL, Kossoff EH. Comorbidity of migraine in children presenting with epilepsy to a tertiary care center. Neurology. 2012;79(5):468–73.PubMedCrossRefGoogle Scholar
  20. 20.
    Schankin CJ, Rémi J, Klaus I, et al. Headache in juvenile myoclonic epilepsy. J Headache Pain. 2011;12(2):227–33.PubMedCrossRefGoogle Scholar
  21. 21.
    Baldin E, Ludvigsson P, Mixa O, Hesdorffer DC. Prevalence of recurrent symptoms and their association with epilepsy and febrile seizure in school-aged children: a community-based survey in Iceland. Epilepsy Behav. 2012;23(3):315–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Duchaczek B, Ghaeni L, Matzen J, Holtkamp M. Interictal and periictal headache in patients with epilepsy. Eur J Neurol. 2012;25:1–7.Google Scholar
  23. 23.
    Tonini MC, Giordano L, Atzeni L, et al. Primary headache and epilepsy: a multicenter cross-sectional study. Epilepsy Behav. 2012;23(3):342–7.PubMedCrossRefGoogle Scholar
  24. 24.
    Winawer MR, Connors R. Evidence for a shared genetic susceptibility to migraine and epilepsy. Epilepsia. 2013. doi:10.1111/epi.12072.Google Scholar
  25. 25.
    Berg AT, Berkovic SF, Brodie MJ, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia. 2010;51(4):676–85.PubMedCrossRefGoogle Scholar
  26. 26.
    Verrotti A, Striano P, Belcastro V, et al. Migralepsy and related conditions: advances in pathophysiology and classification. Seizure. 2011;20(4):271–5.PubMedCrossRefGoogle Scholar
  27. 27.
    Sances G, Guaschino E, Perucca P. Migralepsy: a call for a revision of the definition. Epilepsia. 2009;50(11):2487–96.PubMedCrossRefGoogle Scholar
  28. 28.
    Belcastro V, Striano P, Villa MP, Parisi P. Migralepsy, hemicrania epileptica, post-ictal headache and “ictal epileptic headache”: a proposal for terminology and classification revision. J Headache Pain. 2011;12(3):289–94.PubMedCrossRefGoogle Scholar
  29. 29.
    Parisi P, Striano P, Kasteleijn-Nolst Trenité DGA, et al. “Ictal epileptic headache”: recent concepts for new classifications criteria. Cephalalgia. 2012;32(9):723–4.PubMedCrossRefGoogle Scholar
  30. 30.
    Dainese F, Mai R, Francione S, et al. Ictal headache: headache as first ictal symptom in focal epilepsy. Epilepsy Behav. 2011;22(4):790–2.PubMedCrossRefGoogle Scholar
  31. 31.
    Fanella M, Fattouch J, Casciato S, et al. Ictal epileptic headache as “subtle” symptom in generalized idiopathic epilepsy. Epilepsia. 2012;53(4):e67–70.PubMedCrossRefGoogle Scholar
  32. 32.
    • Adcock JE, Panayiotopoulos CP. Occipital lobe seizures and epilepsies. J Clin Neurophysiol. 2012;29(5):397–407. This review gives a very complete overview of occipital lobe seizures.PubMedCrossRefGoogle Scholar
  33. 33.
    Haan J, Terwindt GM, Van den Maagdenberg AMJM, et al. A review of the genetic relation between migraine and epilepsy. Cephalalgia. 2008;28(2):105–13.PubMedGoogle Scholar
  34. 34.
    Anttila V, Stefansson H, Kallela M, et al. Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1. Nat Genet. 2010;42(10):869–73.PubMedCrossRefGoogle Scholar
  35. 35.
    De Vries B, Frants RR, Ferrari MD, Van den Maagdenberg AMJM. Molecular genetics of migraine. Hum Genet. 2009;126(1):115–32.PubMedCrossRefGoogle Scholar
  36. 36.
    Freilinger T, Anttila V, De Vries B, et al. Genome-wide association analysis identifies susceptibility loci for migraine without aura. Nat Genet. 2012;44(7):777–82.PubMedCrossRefGoogle Scholar
  37. 37.
    Tan NCK, Berkovic SF. The Epilepsy Genetic Association Database (epiGAD): analysis of 165 genetic association studies, 1996-2008. Epilepsia. 2010;51(4):686–9.PubMedCrossRefGoogle Scholar
  38. 38.
    Frosk P, Mhanni AA, Rafay MF. SCNIA mutation associated with intractable myoclonic epilepsy and migraine headache. J Child Neurol. 2012. doi:10.1177/0883073812443309. 1-4.PubMedGoogle Scholar
  39. 39.
    Magis D, Boon E, Coppola G, et al. A novel CACNA1A mutation results in episodic ataxia with migrainous features without headache. Cephalalgia. 2012;32(15):1147–9.PubMedCrossRefGoogle Scholar
  40. 40.
    Marini C, Conti V, Mei D, et al. PRRT2 mutations in familial infantile seizures, paroxysmal dyskinesia, and hemiplegic migraine. Neurology. 2012;79(21):2109–14.PubMedCrossRefGoogle Scholar
  41. 41.
    Gardiner AR, Bhatia KP, Stamelou M, et al. PRRT2 gene mutations: from paroxysmal dyskinesia to episodic ataxia and hemiplegic migraine. Neurology. 2012;79(21):2115–21.PubMedCrossRefGoogle Scholar
  42. 42.
    Méneret A, Gaudebout C, Riant F, et al. PRRT2 mutations and paroxysmal disorders. Eur J Neurol. 2013. doi:10.1111/ene.12104.PubMedGoogle Scholar
  43. 43.
    Polvi A, Siren A, Kallela M, et al. Shared loci for migraine and epilepsy on chromosomes 14q12-q23 and 12q24.2-q24.3. Neurology. 2012;78(3):202–9.PubMedCrossRefGoogle Scholar
  44. 44.
    Somjen GG. Ion regulation in the brain: implications for pathophysiology. Neuroscientist. 2002;8:254–67.PubMedGoogle Scholar
  45. 45.
    Coppola G, Schoenen J. Cortical excitability in chronic migraine. Curr Pain Headache Rep. 2012;16(1):93–100.PubMedCrossRefGoogle Scholar
  46. 46.
    Badawy RAB, Harvey AS, Macdonell RAL. Cortical hyperexcitability and epileptogenesis: understanding the mechanisms of epilepsy - part 1. J Clin Neurosci. 2009;16(3):355–65.PubMedCrossRefGoogle Scholar
  47. 47.
    Garza-López E, Sandoval A, González-Ramírez R, et al. Familial hemiplegic migraine type 1 mutations W1684R and V1696I alter G protein-mediated regulation of Ca(V)2.1 voltage-gated calcium channels. Biochim Biophys Acta. 2012;1822(8):1238–46.PubMedCrossRefGoogle Scholar
  48. 48.
    Badawy RAB, Curatolo JM, Newton M, et al. Changes in cortical excitability differentiate generalized and focal epilepsy. Ann Neurol. 2007;61(4):324–31.PubMedCrossRefGoogle Scholar
  49. 49.
    Mulleners WM, Chronicle EP, Palmer JE, et al. Visual cortex excitability in migraine with and without aura. Headache. 2001;41(6):565–72.PubMedCrossRefGoogle Scholar
  50. 50.
    Van Der Kamp W, Maassenvandenbrink A, Ferrari MD, Van Dijk G. Interictal cortical excitability to magnetic stimulation in familial hemiplegic migraine. Neurology. 1997;1:1996–8.Google Scholar
  51. 51.
    •• Badawy RAB, Jackson GD. Cortical excitability in migraine and epilepsy: a common feature? J Clin Neurophysiol. 2012;29(3):244–9. This is, to our knowledge, the first study to directly compare cortical excitability in epilepsy and migraine.PubMedCrossRefGoogle Scholar
  52. 52.
    Merlo D, Mollinari C, Inaba Y, et al. Reduced GABAB receptor subunit expression and paired-pulse depression in a genetic model of absence seizures. Neurobiol Dis. 2007;25(3):631–41.PubMedCrossRefGoogle Scholar
  53. 53.
    Mathew J, Balakrishnan S, Antony S, et al. Decreased GABA receptor in the cerebral cortex of epileptic rats: effect of Bacopa monnieri and Bacoside-A. J Biomed Sci. 2012;19(1):25.PubMedCrossRefGoogle Scholar
  54. 54.
    Brown JT, Gill CH, Farmer CE, et al. Mechanisms contributing to the exacerbated epileptiform activity in hippocampal slices of GABA B1 receptor subunit knockout mice. Epilepsy Res. 2003;57(2–3):121–36.PubMedCrossRefGoogle Scholar
  55. 55.
    Holland PR, Akerman S, Goadsby PJ. Cortical spreading depression-associated cerebral blood flow changes induced by mechanical stimulation are modulated by AMPA and GABA receptors. Cephalalgia. 2010;30(5):519–27.PubMedGoogle Scholar
  56. 56.
    Plummer PN, Colson NJ, Lewohl JM, et al. Significant differences in gene expression of GABA receptors in peripheral blood leukocytes of migraineurs. Gene. 2011;490(1–2):32–6.PubMedCrossRefGoogle Scholar
  57. 57.
    Russo L, Mariotti P, Sangiorgi E, et al. A new susceptibility locus for migraine with aura in the 15q11-q13 genomic region containing three GABA-A receptor genes. Am J Hum Genet. 2005;76(2):327–33.PubMedCrossRefGoogle Scholar
  58. 58.
    Oswell G, Kaunisto MA, Kallela M, et al. No association of migraine to the GABA-A receptor complex on chromosome 15. Am J Med Genet. 2008;147B(1):33–6.PubMedCrossRefGoogle Scholar
  59. 59.
    Netzer C, Freudenberg J, Toliat MR, et al. Genetic association studies of the chromosome 15 GABA-A receptor cluster in migraine with aura. Am J Med Genet. 2008;147B(1):37–41.PubMedCrossRefGoogle Scholar
  60. 60.
    Fernandez F, Esposito T, Lea RA, et al. Investigation of gamma-aminobutyric acid (GABA) A receptors genes and migraine susceptibility. BMC Med Genet. 2008;9:109.PubMedCrossRefGoogle Scholar
  61. 61.
    Wallace RH, Marini C, Petrou S, et al. Mutant GABA(A) receptor gamma2-subunit in childhood absence epilepsy and febrile seizures. Nat Genet. 2001;28(1):49–52.PubMedGoogle Scholar
  62. 62.
    Baulac S, Huberfeld G, Gourfinkel-An I, et al. First genetic evidence of GABA(A) receptor dysfunction in epilepsy: a mutation in the gamma2-subunit gene. Nat Genet. 2001;28(1):46–8.PubMedGoogle Scholar
  63. 63.
    Lachance-Touchette P, Brown P, Meloche C, et al. Novel α1 and γ2 GABAA receptor subunit mutations in families with idiopathic generalized epilepsy. Eur J Neurosci. 2011;34(2):237–49.PubMedCrossRefGoogle Scholar
  64. 64.
    Lauritzen M, Dreier JP, Fabricius M. Clinical relevance of cortical spreading depression in neurological disorders: migraine, malignant stroke, subarachnoid and intracranial hemorrhage, and traumatic brain injury. J Cereb Blood Flow Metab. 2011;31(1):17–35.PubMedCrossRefGoogle Scholar
  65. 65.
    • Dreier JP. The role of spreading depression, spreading depolarization and spreading ischemia in neurological disease. Nat Med. 2011;17(4):439–47. This review addresses the complex issue of spreading depolarization and gives an overview of the current understanding of this phenomenon in relation to neurologic conditions.PubMedCrossRefGoogle Scholar
  66. 66.
    Herreras O, Largo C, Ibarz JM, et al. Role of neuronal synchronizing mechanisms in the propagation of spreading depression in the in vivo hippocampus. J Neurosci. 1994;14(11):7087–98.PubMedGoogle Scholar
  67. 67.
    Larrosa B, Pastor J, López-Aguado L, Herreras O. A role for glutamate and glia in the fast network oscillations preceding spreading depression. Neuroscience. 2006;141(2):1057–68.PubMedCrossRefGoogle Scholar
  68. 68.
    Mayevsky A, Doron A, Manor T, et al. Cortical spreading depression recorded from the human brain using a multiparametric monitoring system. Brain Res. 1996;740(1–2):268–74.PubMedCrossRefGoogle Scholar
  69. 69.
    Strong AJ, Fabricius M, Boutelle MG, et al. Spreading and synchronous depressions of cortical activity in acutely injured human brain. Stroke. 2002;33(12):2738–43.PubMedCrossRefGoogle Scholar
  70. 70.
    Fabricius M, Fuhr S, Bhatia R, et al. Cortical spreading depression and peri-infarct depolarization in acutely injured human cerebral cortex. Brain. 2006;129:778–90.PubMedCrossRefGoogle Scholar
  71. 71.
    •• Dreier JP, Major S, Pannek H-W, et al. Spreading convulsions, spreading depolarization and epileptogenesis in human cerebral cortex. Brain. 2012;135:259–75. This study demonstrates spreading convulsions for the first time in humans, and links cortical spreading depression to later occurrence of epilepsy.PubMedCrossRefGoogle Scholar
  72. 72.
    Tomkins O, Friedman O, Ivens S, et al. Blood-brain barrier disruption results in delayed functional and structural alterations in the rat neocortex. Neurobiol Dis. 2007;25(2):367–77.PubMedCrossRefGoogle Scholar
  73. 73.
    Fabricius M, Fuhr S, Willumsen L, et al. Association of seizures with cortical spreading depression and peri-infarct depolarisations in the acutely injured human brain. Clin Neurophysiol. 2009;119(9):1973–84.CrossRefGoogle Scholar
  74. 74.
    Gorji A, Speckmann E. Spreading depression enhances the spontaneous epileptiform activity in human neocortical tissues. Eur J Neurosci. 2004;19:3371–4.PubMedCrossRefGoogle Scholar
  75. 75.
    Krüger H, Luhmann HJ, Heinemann U. Repetitive spreading depression causes selective suppression of GABAergic function. NeuroReport. 1996;7:2733–6.PubMedCrossRefGoogle Scholar
  76. 76.
    Maslarova A, Alam M, Reiffurth C, et al. Chronically epileptic human and rat neocortex display a similar resistance against spreading depolarization in vitro. Stroke. 2011;42(10):2917–22.PubMedCrossRefGoogle Scholar
  77. 77.
    Van den Maagdenberg AMJM, Pietrobon D, Pizzorusso T, et al. A Cacna1a knockin migraine mouse model with increased susceptibility to cortical spreading depression. Neuron. 2004;41(5):701–10.PubMedCrossRefGoogle Scholar
  78. 78.
    •• Van den Maagdenberg AMJM, Pizzorusso T, Kaja S, et al. High cortical spreading depression susceptibility and migraine-associated symptoms in Ca(v)2.1 S218L mice. Ann Neurol. 2010;67(1):85–98. This study demonstrates that a CACNA1A mutation in mice can lead to a higher susceptibility for cortical spreading depresion.PubMedCrossRefGoogle Scholar
  79. 79.
    Dreier JP, Sakowitz OW, Unterberg AW, et al. Migrainous aura starting several minutes after the onset of subarachnoid hemorrhage. Neurology. 2001;57(7):1344–5.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • P. R. Bauer
    • 1
  • J. A. Carpay
    • 2
  • G. M. Terwindt
    • 2
  • J. W. Sander
    • 1
    • 3
    • 4
  • R. J. Thijs
    • 1
    • 2
  • J. Haan
    • 2
    • 5
  • G. H. Visser
    • 1
  1. 1.SEIN Epilepsy Institute in the Netherlands Foundation, Heemstede, The NetherlandsHoofddorpThe Netherlands
  2. 2.Department of NeurologyLeiden University Medical CentreLeidenThe Netherlands
  3. 3.NIHR University College London Hospitals Biomedical Research CentreUCL Institute of NeurologyLondonUK
  4. 4.Epilepsy SocietyChalfont St PeterUK
  5. 5.Department of NeurologyRijnland Hospital LeiderdorpLeiderdorpThe Netherlands

Personalised recommendations