Migraine, Stroke and Epilepsy: Underlying and Interrelated Causes, Diagnosis and Treatment

Opinion statement

Migraine, epilepsy and stroke are highly prevalent neurological disorders, often comorbid. They share diverse pathophysiological mechanisms that explain the use of similar drugs on certain occasions (i.e., the use of antiepileptic drugs in migraine prevention). Migraine with aura represents a risk for ischemic stroke, and avoiding contraceptives, tobacco use, and ergot alkaloids should be advised in those patients. Epilepsy bears a bidirectional relationship with headache. Only three entities are considered as seizure-related headaches: migraine-triggered seizure (migralepsy), hemicrania epileptica, and post-ictal headache. Topiramate (100–200 mg daily) and valproic acid (500–1,000 mg daily) are first-line drugs in migraine prevention, while older antiepileptics have no use in this setting. Stroke is the most common cause of symptomatic epilepsy in the adult. Therapy with lamotrigine, gabapentine, and levetiracetam is advised in late-onset (2 weeks after stroke) stroke-seizures, while early-onset seizures usually do not require therapy.

This is a preview of subscription content, access via your institution.

Figure 1
Figure 2
Figure 3

References and Recommended Reading

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

  1. 1.

    Parisi P, Striano P, Negro A, et al. Ictal epileptic headache: an old story with courses and appeals. J Headache Pain. 2012;13(8):607–13.

    PubMed  Article  Google Scholar 

  2. 2.

    Belcastro V, Striano P, Parisi P. From migralepsy to ictal epileptic headache: the story so far. Neurol Sci. 2012.

  3. 3.•

    Papetti L, Nicita F, Parisi P, et al. "Headache and epilepsy"—How are they connected? Epilepsy Behav. 2012. Reviews the relationship between migraine and epilepsy: epidemiology and pathophysiology, clinical correlations and classification.

  4. 4.•

    Kurth T, Diener HC. Migraine and stroke: perspectives for stroke physicians. Stroke. 2012;43(12):3421–6. A review of the epidemiologycal evidence linking migraine and stroke and practical consequences.

    PubMed  Article  Google Scholar 

  5. 5.

    Spector JT, Kahn SR, Jones MR, et al. Migraine headache and ischemic stroke risk: an updated meta-analysis. Am J Med. 2010;123(7):612–24.

    PubMed  Article  Google Scholar 

  6. 6.

    Stewart WF, Shechter A, Rasmussen BK. Migraine prevalence. A review of population-based studies. Neurology. 1994;44(6 Suppl 4):S17–23.

    PubMed  CAS  Google Scholar 

  7. 7.

    Tonini MC, Giordano L, Atzeni L, et al. Primary headache and epilepsy: a multicenter cross-sectional study. Epilepsy Behav. 2012;23(3):342–7.

    PubMed  Article  CAS  Google Scholar 

  8. 8.

    Larrosa-Campo D, Ramon-Carbajo C, Para-Prieto M, et al. [Migraine as a vascular risk factor]. Rev Neurol. 2012;55(6):349–58.

    PubMed  Google Scholar 

  9. 9.••

    Kurth T, Chabriat H, Bousser MG. Migraine and stroke: a complex association with clinical implications. Lancet Neurol. 2012;11(1):92–100.This article explains current hypotheses on the common pathophysiology between migraine and stroke and its clinical implications.

    PubMed  Article  Google Scholar 

  10. 10.

    Sarchielli P, Alberti A, Coppola F, et al. Platelet-activating factor (PAF) in internal jugular venous blood of migraine without aura patients assessed during migraine attacks. Cephalalgia. 2004;24(8):623–30.

    PubMed  Article  CAS  Google Scholar 

  11. 11.

    Kitano A, Shimomura T, Takeshima T, Takahashi K. Increased 11-dehydrothromboxane B2 in migraine: platelet hyperfunction in patients with migraine during headache-free period. Headache. 1994;34(9):515–8.

    PubMed  Article  CAS  Google Scholar 

  12. 12.

    Htun P, Fateh-Moghadam S, Tomandl B, et al. Course of platelet activation and platelet-leukocyte interaction in cerebrovascular ischemia. Stroke. 2006;37(9):2283–7.

    PubMed  Article  CAS  Google Scholar 

  13. 13.

    Jesurum JT, Fuller CJ, Murinova N, et al. Aspirin's effect on platelet inhibition in migraineurs. Headache. 2012;52(8):1207–18.

    PubMed  Article  Google Scholar 

  14. 14.

    Post MC, Thijs V, Herroelen L, Budts WI. Closure of a patent foramen ovale is associated with a decrease in prevalence of migraine. Neurology. 2004;62(8):1439–40.

    PubMed  Article  Google Scholar 

  15. 15.

    Morandi E, Anzola GP, Angeli S, et al. Transcatheter closure of patent foramen ovale: a new migraine treatment? J Interv Cardiol. 2003;16(1):39–42.

    PubMed  Article  Google Scholar 

  16. 16.

    Wilmshurst PT, Nightingale S, Walsh KP, Morrison WL. Effect on migraine of closure of cardiac right-to-left shunts to prevent recurrence of decompression illness or stroke or for haemodynamic reasons. Lancet. 2000;356(9242):1648–51.

    PubMed  Article  CAS  Google Scholar 

  17. 17.

    Schwerzmann M, Wiher S, Nedeltchev K, et al. Percutaneous closure of patent foramen ovale reduces the frequency of migraine attacks. Neurology. 2004;62(8):1399–401.

    PubMed  Article  CAS  Google Scholar 

  18. 18.

    Dowson A, Mullen MJ, Peatfield R, et al. Migraine Intervention with STARFlex Technology (MIST) trial: a prospective, multicenter, double-blind, sham-controlled trial to evaluate the effectiveness of patent foramen ovale closure with STARFlex septal repair implant to resolve refractory migraine headache. Circulation. 2008;117(11):1397–404.

    PubMed  Article  Google Scholar 

  19. 19.

    Swartz RH, Kern RZ. Migraine is associated with magnetic resonance imaging white matter abnormalities: a meta-analysis. Arch Neurol. 2004;61(9):1366–8.

    PubMed  Article  Google Scholar 

  20. 20.

    Laurell K, Lundstrom E. Migrainous infarction: aspects on risk factors and therapy. Curr Pain Headache Rep. 2012;16(3):255–60.

    PubMed  Article  Google Scholar 

  21. 21.

    Metso TM, Tatlisumak T, Debette S, et al. Migraine in cervical artery dissection and ischemic stroke patients. Neurology. 2012;78(16):1221–8.

    PubMed  Article  CAS  Google Scholar 

  22. 22.

    Sacco S, Ricci S, Carolei A. Migraine and vascular diseases: a review of the evidence and potential implications for management. Cephalalgia. 2012;32(10):785–95.

    PubMed  Article  Google Scholar 

  23. 23.

    Schwedt TJ. The migraine association with cardiac anomalies, cardiovascular disease, and stroke. Neurol Clin. 2009;27(2):513–23.

    PubMed  Article  Google Scholar 

  24. 24.

    Ryan DP, Ptacek LJ. Episodic neurological channelopathies. Neuron. 2010;68(2):282–92.

    PubMed  Article  CAS  Google Scholar 

  25. 25.

    Rogawski M. Migraine and epilepsy—shared mechanisms within the family of episodic disorders. In: Noebels JL, Avoli M, Rogawski MA, et al., editors. Jasper's basic mechanisms of the epilepsies [Internet]. 4th ed. Bethesda: National Center for Biotechnology Information (US); 2012. p. 1–17.

    Google Scholar 

  26. 26.

    Lipton RB, Bigal ME, Diamond M, et al. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology. 2007;68(5):343–9.

    PubMed  Article  CAS  Google Scholar 

  27. 27.

    Toldo I, Perissinotto E, Menegazzo F, et al. Comorbidity between headache and epilepsy in a pediatric headache center. J Headache Pain. 2010;11(3):235–40.

    PubMed  Article  Google Scholar 

  28. 28.

    Silberstein SD, Lipton R, Haut S. Migraine. In: Engel JJ, Pedley TA, editors. Epilepsy: A comprehensive Textbook 2. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins; 2008. p. 2733–43.

    Google Scholar 

  29. 29.

    Society HCCotIH. The international classification of headache disorders: 2nd edition. Cephalalgia 2004;24(Suppl. 1):9–160.

    Google Scholar 

  30. 30.

    Sances G, Guaschino E, Perucca P, et al. Migralepsy: a call for a revision of the definition. Epilepsia. 2009;50(11):2487–96.

    PubMed  Article  Google Scholar 

  31. 31.

    Verrotti A, Coppola G, Di Fonzo A, et al. Should "migralepsy" be considered an obsolete concept? A multicenter retrospective clinical/EEG study and review of the literature. Epilepsy Behav. 2011;21(1):52–9.

    PubMed  Article  Google Scholar 

  32. 32.

    Panayiotopoulos CP. Visual phenomena and headache in occipital epilepsy: a review, a systematic study and differentiation from migraine. Epileptic Disord. 1999;1(4):205–16.

    PubMed  CAS  Google Scholar 

  33. 33.

    Kasteleijn-Nolst Trenite D, Parisi P. Migraine in the borderland of epilepsy: "migralepsy" an overlapping syndrome of children and adults? Epilepsia. 2012;53 Suppl 7:20–5.

    PubMed  Article  Google Scholar 

  34. 34.

    Parisi P, Striano P, Trenite DG, et al. 'Ictal epileptic headache': recent concepts for new classifications criteria. Cephalalgia. 2012;32(9):723–4.

    PubMed  Article  Google Scholar 

  35. 35.

    Belcastro V, Striano P, Pierguidi L, et al. Ictal epileptic headache mimicking status migrainosus: EEG and DWI-MRI findings. Headache. 2011;51(1):160–2.

    PubMed  Article  Google Scholar 

  36. 36.

    Parisi P. Why is migraine rarely, and not usually, the sole ictal epileptic manifestation? Seizure. 2009;18(5):309–12.

    PubMed  Article  Google Scholar 

  37. 37.

    Belcastro V, Striano P, Kasteleijn-Nolst Trenite DG, et al. 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.

    PubMed  Article  Google Scholar 

  38. 38.

    Fanella M, Fattouch J, Casciato S, et al. Ictal epileptic headache as "subtle" symptom in generalized idiopathic epilepsy. Epilepsia. 2012;53(4):e67–70.

    PubMed  Article  Google Scholar 

  39. 39.

    Group HS. Multi-center study on migraine and seizure-related headache in patients with epilepsy. Yonsei Med J. 2010;51(2):219–24.

    Article  Google Scholar 

  40. 40.

    Bianchin MM, Londero RG, Lima JE, Bigal ME. Migraine and epilepsy: a focus on overlapping clinical, pathophysiological, molecular, and therapeutic aspects. Curr Pain Headache Rep. 2010;14(4):276–83.

    PubMed  Article  Google Scholar 

  41. 41.

    Verrotti A, Coppola G, Spalice A, et al. Peri-ictal and inter-ictal headache in children and adolescents with idiopathic epilepsy: a multicenter cross-sectional study. Childs Nerv Syst. 2011;27(9):1419–23.

    PubMed  Article  Google Scholar 

  42. 42.

    Ito M, Adachi N, Nakamura F, et al. Characteristics of postictal headache in patients with partial epilepsy. Cephalalgia. 2004;24(1):23–8.

    PubMed  Article  CAS  Google Scholar 

  43. 43.

    Velioglu SK, Boz C, Ozmenoglu M. The impact of migraine on epilepsy: a prospective prognosis study. Cephalalgia. 2005;25(7):528–35.

    PubMed  Article  CAS  Google Scholar 

  44. 44.

    Verrotti A, Striano P, Belcastro V, et al. Migralepsy and related conditions: advances in pathophysiology and classification. Seizure. 2011;20(4):271–5.

    PubMed  Article  Google Scholar 

  45. 45.

    Parisi P, Piccioli M, Villa MP, et al. Hypothesis on neurophysiopathological mechanisms linking epilepsy and headache. Med Hypotheses. 2008;70(6):1150–4.

    PubMed  Article  Google Scholar 

  46. 46.

    Berger M, Speckmann EJ, Pape HC, Gorji A. Spreading depression enhances human neocortical excitability in vitro. Cephalalgia. 2008;28(5):558–62.

    PubMed  Article  CAS  Google Scholar 

  47. 47.

    Rogawski MA. Antiepileptic drugs and migraine. In: Olesen J RN, editor. Innovative drug development for headache disorders (Frontiers in headache research volume 16): Oxford University Press; 2008. p. 153–78.

  48. 48.

    D'Amico D. Pharmacological prophylaxis of chronic migraine: a review of double-blind placebo-controlled trials. Neurol Sci. 2010;31 Suppl 1:S23–8.

    PubMed  Article  Google Scholar 

  49. 49.

    Welch KM. Brain hyperexcitability: the basis for antiepileptic drugs in migraine prevention. Headache. 2005;45 Suppl 1:S25–32.

    PubMed  Article  Google Scholar 

  50. 50.

    Eijkelkamp N, Linley JE, Baker MD, et al. Neurological perspectives on voltage-gated sodium channels. Brain. 2012;135(Pt 9):2585–612.

    PubMed  Article  Google Scholar 

  51. 51.

    Lenaerts ME, Oommen KJ, Couch JR, Skaggs V. Can vagus nerve stimulation help migraine? Cephalalgia. 2008;28(4):392–5.

    PubMed  Article  CAS  Google Scholar 

  52. 52.

    Basic S, Sporis D, Chudy D, et al. The effect of vagus nerve stimulation on migraine in patient with intractable epilepsy: case report. Neurol Sci. 2012.

  53. 53.

    Schurks M. Genetics of migraine in the age of genome-wide association studies. J Headache Pain. 2012;13(1):1–9.

    PubMed  Article  Google Scholar 

  54. 54.

    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.

    PubMed  Article  CAS  Google Scholar 

  55. 55.

    Lebas A G-ME, Guyant-Maréchal L. Epilepsy and familial hemiplegic migraine. Genetic and clinical aspects. In: Parain D GR, Hesdorffer D, Ryvlin P, editor. Epilepsy and migraine: John Libby Eurotext; 2009.

  56. 56.

    Vikelis M, Rapoport AM. Role of antiepileptic drugs as preventive agents for migraine. CNS Drugs. 2010;24(1):21–33.

    PubMed  Article  CAS  Google Scholar 

  57. 57.

    Pelzer N, Stam AH, Haan J, et al. Familial and sporadic hemiplegic migraine: diagnosis and treatment. Curr Treat Options Neurol. 2012.

  58. 58.

    Ramsay RE, Rowan AJ, Pryor FM. Special considerations in treating the elderly patient with epilepsy. Neurology. 2004;62(5 Suppl 2):S24–9.

    PubMed  Article  Google Scholar 

  59. 59.

    Hesdorffer DC, Logroscino G, Benn EK, et al. Estimating risk for developing epilepsy: a population-based study in Rochester, Minnesota. Neurology. 2011;76(1):23–7.

    PubMed  Article  CAS  Google Scholar 

  60. 60.

    So EL, Annegers JF, Hauser WA, et al. Population-based study of seizure disorders after cerebral infarction. Neurology. 1996;46(2):350–5.

    PubMed  Article  CAS  Google Scholar 

  61. 61.

    Ribacoba-Montero R, Pujols-Castillo Y, Vallina-Garcia MI, et al. [Clinical epidemiological study of vascular epilepsy]. Rev Neurol. 2007;45(12):719–24.

    PubMed  CAS  Google Scholar 

  62. 62.

    Benbir G, Ince B, Bozluolcay M. The epidemiology of post-stroke epilepsy according to stroke subtypes. Acta Neurol Scand. 2006;114(1):8–12.

    PubMed  Article  CAS  Google Scholar 

  63. 63.

    De Reuck J, Goethals M, Vonck K, Van Maele G. Clinical predictors of late-onset seizures and epilepsy in patients with cerebrovascular disease. Eur Neurol. 2005;54(2):68–72.

    PubMed  Article  Google Scholar 

  64. 64.

    Lossius MI, Ronning OM, Slapo GD, et al. Poststroke epilepsy: occurrence and predictors–a long-term prospective controlled study (Akershus Stroke Study). Epilepsia. 2005;46(8):1246–51.

    PubMed  Article  Google Scholar 

  65. 65.

    Lamy C, Domigo V, Semah F, et al. Early and late seizures after cryptogenic ischemic stroke in young adults. Neurology. 2003;60(3):400–4.

    PubMed  Article  CAS  Google Scholar 

  66. 66.

    De Reuck J, De Groote L, Van Maele G. Single seizure and epilepsy in patients with a cerebral territorial infarct. J Neurol Sci. 2008;271(1–2):127–30.

    PubMed  Article  Google Scholar 

  67. 67.

    Procaccianti G, Zaniboni A, Rondelli F, et al. Seizures in acute stroke: incidence, risk factors and prognosis. Neuroepidemiology. 2012;39(1):45–50.

    PubMed  Article  Google Scholar 

  68. 68.

    Jung S, Schindler K, Findling O, et al. Adverse effect of early epileptic seizures in patients receiving endovascular therapy for acute stroke. Stroke. 2012;43(6):1584–90.

    PubMed  Article  Google Scholar 

  69. 69.

    De Reuck J, De Clerck M, Van Maele G. Vascular cognitive impairment in patients with late-onset seizures after an ischemic stroke. Clin Neurol Neurosurg. 2006;108(7):632–7.

    PubMed  Article  Google Scholar 

  70. 70.

    Naidech AM, Kreiter KT, Janjua N, et al. Phenytoin exposure is associated with functional and cognitive disability after subarachnoid hemorrhage. Stroke. 2005;36(3):583–7.

    PubMed  Article  CAS  Google Scholar 

  71. 71.

    Cleary P, Shorvon S, Tallis R. Late-onset seizures as a predictor of subsequent stroke. Lancet. 2004;363(9416):1184–6.

    PubMed  Article  Google Scholar 

  72. 72.

    Velioglu SK, Ozmenoglu M, Boz C, Alioglu Z. Status epilepticus after stroke. Stroke. 2001;32(5):1169–72.

    PubMed  Article  CAS  Google Scholar 

  73. 73.••

    Ryvlin P, Montavont A, Nighoghossian N. Optimizing therapy of seizures in stroke patients. Neurology. 2006;67(12 Suppl 4):S3–9.Details the reasoning for choosing a particular antiepileptic drug according to the levels of evidence of the literature.

    PubMed  Article  Google Scholar 

  74. 74.

    Gilad R. Management of seizures following a stroke: what are the options? Drugs Aging. 2012;29(7):533–8.

    PubMed  Article  CAS  Google Scholar 

  75. 75.

    Menon B, Shorvon SD. Ischaemic stroke in adults and epilepsy. Epilepsy Res. 2009;87(1):1–11.

    PubMed  Article  Google Scholar 

  76. 76.

    Arain AM, Abou-Khalil BW. Management of new-onset epilepsy in the elderly. Nat Rev Neurol. 2009;5(7):363–71.

    PubMed  Article  CAS  Google Scholar 

  77. 77.

    Rowan AJ, Ramsay RE, Collins JF, et al. New onset geriatric epilepsy: a randomized study of gabapentin, lamotrigine, and carbamazepine. Neurology. 2005;64(11):1868–73.

    PubMed  Article  CAS  Google Scholar 

  78. 78.

    Saetre E, Perucca E, Isojarvi J, et al. An international multicenter randomized double-blind controlled trial of lamotrigine and sustained-release carbamazepine in the treatment of newly diagnosed epilepsy in the elderly. Epilepsia. 2007;48(7):1292–302.

    PubMed  Article  CAS  Google Scholar 

Download references

Disclosure

Dr. Aida Rodriguez-Sainz reported no conflicts of interest relevant to this article.

Dr. Ana Pinedo-Brochado reported no conflicts of interest relevant to this article.

Dr. Jose L. Sánchez-Menoyo reported no conflicts of interest relevant to this article.

Dr. Javier Ruiz-Ojeda reported no conflicts of interest relevant to this article.

Dr. Ines Escalza-Cortina reported no conflicts of interest relevant to this article.

Dr. Juan Carlos Garcia-Monco reported no conflicts of interest relevant to this article.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Juan Carlos Garcia-Monco MD.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Rodriguez-Sainz, A., Pinedo-Brochado, A., Sánchez-Menoyo, J.L. et al. Migraine, Stroke and Epilepsy: Underlying and Interrelated Causes, Diagnosis and Treatment. Curr Treat Options Cardio Med 15, 322–334 (2013). https://doi.org/10.1007/s11936-013-0236-7

Download citation

Keywords

  • Stroke
  • Migraine
  • Epilepsy
  • Seizures
  • Vascular epilepsy