Migraine and epilepsy are comorbid. Andermann and Andermann (1987) reported a median epilepsy prevalence of 5.9% (range 1% to 17%) in migraineurs, which greatly exceeds the population prevalence of 0.5% (Hauser et al., 1991). The reported migraine prevalence in epileptics ranges from 8% to 23% (Olesen, 1993). Methodologic problems make these studies difficult to interpret (Olesen, 1993).
The comorbidity of migraine and epilepsy was studied using Columbia University’s Epilepsy Family Study (Ottman and Lipton, 1994, 1996; Lipton et al., 1994). Among subjects with epilepsy (probands), the prevalence of a migraine history was 24%. Among relatives with epilepsy, 26% had a history of migraine. In control relatives without epilepsy, the prevalence of a migraine history was 15%. The relative risk of migraine in persons with epilepsy was 2.4, for both probands and their epileptic relatives. Migraine risk was not related to age at epilepsy onset (partial vs. generalized) but was highest in post-traumatic epileptics (RR = 4.1).
Using reconstructed cohort methods, migraine risk is elevated both before and after seizure onset; therefore, it cannot be accounted for solely as a cause or solely as a consequence of epilepsy (Ottman and Lipton, 1994, 1996; Lipton et al., 1994). Because migraine risk is particularly elevated in post-traumatic epileptics and head injury is also a risk factor for both disorders, shared environmental risk factors may contribute to their comorbidity (Shechter et al., 1990; Annergers et al., 1980). However, known environmental risk factors cannot fully account for this comorbidity because migraine risk is also elevated in individuals with idiopathic epilepsy. Shared genetic risk factors cannot completely account for comorbidity as migraine risk is elevated in probands with and without a positive family history of epilepsy.
Perhaps an altered brain state increases the risk of both migraine and epilepsy and, thus, accounts for the comorbidity of these disorders (Welch, 1994; Hauser et al., 1991). Genetic or environmental risk factors may increase neuronal excitability or decrease the threshold to both types of attack. A reduction in brain magnesium (Welch et al., 1991) or alterations in neurotransmitters provide plausible potential substrates for this alteration in neuronal excitability (Welch, 1987; Welch et al., 1991; Olesen, 1993).
The association between migraine and epilepsy has implications for clinical practice.
When treating patients for one disorder, it is important to maintain a heightened index of suspicion for the other disorder. Differentiating migraine and epilepsy can be difficult (Andermann and Andermann, 1987; Marks and Ehrenberg, 1993) as both conditions are characterized by episodes of neurologic dysfunction. Headache without other neurologic features is rare as a manifestation of epilepsy. The most difficult diagnostic issue is differentiating migraine with aura from partial complex seizure. If the aura is brief (less than 5 minutes) and associated with alteration of consciousness, automatisms, and other positive motor features (tonic-clonic movements), epilepsy is more likely. If the aura is of long duration (more than 5 minutes) and has a mix of positive (scintillations, tingling) and negative (visual loss, numbness) features, migraine is more likely.
Treatment strategies for patients with comorbid migraine and epilepsy should be governed by the presence of comorbid disease. For example, drugs that lower seizure threshold should be used cautiously. Examples of such drugs include tricyclic antidepressants, selective serotonin reuptake inhibitors, and neuroleptics. However, it is sometimes advantageous to treat both migraine and epilepsy with a single drug, such as divalproex sodium (Jensen et al., 1994), gabapentin, or topiramate.
- Alvarez, J., J. Matias-Guiu, and J. Sumalla (1989). Ischemic stroke in young adults: Analysis of etiological subgroups. Acta. Neurol. Scand. 80:29 – 34.
- Andermann, E. and F.A. Andermann (1987). Migraine-epilepsy relationships: Epidemiological and genetic aspects. In Migraine and Epilepsy (F.A. Andermann and E. Lugaresi, eds.), pp. 281 – 291. Butter-worths, Boston.
- Annergers, J.F., J.D. Grabow, and R.V. Groover (1980). Seizures after head trauma: A population study. Neurology 30:683 – 689.
- Atkinson, R.A. and O. Appenzeller (1976). Hermicrania and Raynaud’s phenomenon; manifestations of the same disease? Headache 16:l – 3.
- Batista, M.D., T.P. Cartledge, A. Zellmer et al.(1989). The antiprogesterone RU 486 delays ovulation in spontaneous and GnRH induced menstrual cycles [Abstract]. In Endocrine Society 71st Annual Meeting, p. 431. Endocrine Society, Bethesda, MD.
- Biary, N., W. Koller, and P. Langenberg (1990). Correlation between essential tremor and migraine headache. J. Neurol. Neurosurg. Psychiatry 53:1060 – 1062.
- Bougousslavsky, J., P.A. Despland, and F. Regli (1987). Spontaneous dissection with acute stroke. Arch. Neural. 44:137 – 140.
- Bougousslavsky, J. and F. Reglli (1987). Ischemic stroke in adults younger than 30 years of age: Cause and prognosis. Arch. Neurol. 44:479 – 482.
- Brandt, J., D. Celentano, and W.F Stewart (1990). Personality and emotional disorder in a community sample of migraine headache sufferers. Am. J. Psychiatric 147:303 – 308.
- Breslau, N. (1992). Migraine, suicidal ideation, and suicide attempts. Neurology 42:392 – 395.
- Breslau, N. and P. Andreski (1995). Migraine, personality, and psychiatric comorbidity. Headache 35:382 – 386.
- Breslau, N., H.D. Chilcoat, and P. Andreski (1996). Further evidence on the link between migraine and neuroticism. Neurology 47:663 – 667.
- Breslau, N. and G.C. Davis (1992). Migraine, major depression and panic disorder: A prospective epidemiologic study of young adults. Cephalalgia 12:85 – 89.
- Breslau, N. and G.C. Davis (1993). Migraine, physical health and psychiatric disorders: A prospective epidemiologic study of young adults. J. Psychiatry. Res. 27:211 – 221.
- Breslau, N., G.C. Davis, and P. Andreski (1991). Migraine, psychiatric disorders and suicide attempts: An epidemiological study of young adults. J Psychiatry Res. 37:11 – 23.
- Breslau, N., G.C. Davis, L.R. Schultz, and E.L. Peterson (1994a). Migraine and major depression: A longitudinal study. Headache 34:387 – 393.
- Breslau, N., K. Merikangas, and C.L. Bowden (1994b). Comorbidity of migraine and major affective disorders. Neurology 44:17 – 22.
- Breslau, N., L.R. Schultz, W.F. Stewart et al.(2000). Headache and major depression: Is the association specific to migraine? Neurology 54: 308 – 313.
- Brody, M.J. and P.J. Kadowitz (1974). Prostaglandins as modulators of the autonomic nervous system. Fed. Proc. 33:48 – 60.
- Chang, C.L., M. Donaghy, and N. Poulter (1999). Migraine and stroke in young women: Case-control study. The World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. BMJ 318:13 – 18.
- Collaborative Group for the Study of Stroke in Young Women. (1975). Oral contraceptives and stroke in young women. JAMA 231:718 – 722.
- Ettinger, B., G.D. Friedman, T. Bush, and C.P. Quesenberry (1996). Reduced mortality associated with longterm postmenopausal estrogen therapy. Obstet. Gynecol. 87:6 – 12.
- Eysenck, H.J. and S.B. Eysenck (1975). Manual of the Eysenck Personality Questionnaire. Educational and Industrial Testing Service, San Diego.
- Feinstein, A.R. (1970). The pretherapeutic classification of comorbidity in chronic disease. J. Chronic Dis. 23:455 – 468.
- Gamberini, G., R. D’lessandro, E. Labriola et al.(1984). Further evidence on the association of mitral valve prolapse and migraine. Headache 24:39 – 40.
- Goldberg, D. (1975). Manual of the General Health Questionnaire. Educational and Industrial Testing Service, San Diego.
- Hathaway, S.R. and J.C. McKinley (1943). Minnesota Multiphasic Personality Inventory. University of Minnesota, Minneapolis.
- Hauser, W.A., J.F. Annergers, and L.T. Kurland (1991). Prevalence of epilepsy in Rochester, Minnesota. Epilepsia 32:429 – 445.
- Headache Classification Committee of the International Headache Society. (1988). Classification and diagnostic criteria for headache disorders, cranial neuralgia, and facial pain. Cephalalgia 8:1 – 96.
- Henrich, J.B. and R.I. Horowitz (1989). A controlled study of ischemic stroke risk in migraine patients. J. Clin. Epidemiol. 42:773 – 780.
- Henrich, J.B., P.A.G. Sandercock, C.P. Warlow et al. (1986). Stroke and migraine in the Oxfordshire Community Stroke Project J. Neurol. 233: 257 – 262.
- Invernizzi, G., C. Gala, and M. Buono (1989). Neurotic traits and disease duration in headache patients. Cephalalgia 9:173 – 178.
- Isenberg, D.A., D.M. Thomas, M.L. Snaith et al.(1982). A study of migraine in systematic lupus erythematosis. Ann. Rheum. Dis. 41:30 – 32.
- Jarman, J., M. Fernandez, P.T. Davies et al.(1990). High incidence of endogenous depression in migraine: Confirmation of tyramine test. J. Neurol. Neurosurg. Psychiatry 53:573 – 575.
- Jensen, R., T. Brinck, and J. Olesen (1994). Sodium valproate has a prophylactic effect in migraine without aura. Neurology 44:647 – 651.
- Kittner, S.J., R.J. McCarer, and R.W. Sherwin (1993). Black-white differences in stroke among young adults. Stroke 24:113 – 115.
- Kudrow, L. and G.J. Sutkus (1979). MMPI pattern specificity in primary headache disorders. Headache 19:18 – 24.
- Leppert, J., H. Aberg, I. Ringqvist et al. (1987). Raynaud’s phenomenon in a female population: Prevalence and association with other conditions. J. Vase. Dis. 38:871 – 877.
- Lindegaard, O. (1995). Oral contraceptives, pregnancy and the risk of cerebral thromboembolism: The influences of diabetes, hypertension, migraine, and previous thrombotic disease. Br. J. Obstet. Gynaecol. 102:1 – 3.
- Lipton, R.B., R. Ottman, B.L. Ehrenberg et al.(1994). Comorbidity of migraine: The connection between migraine and epilepsy. Neurology 44:28 – 32.
- Lipton, R.B. and S.D. Silberstein (1994). Why study the comorbidity of migraine? Neurology 44:4 – 5.
- Marchesi, C., A. De Ferri, and N. Petrolini (1989). Prevalence of migraine and muscle tension headache in depressive disorders. J. Affect. Disord. 16:33 – 36.
- Marks, D.A. and B.L. Ehrenberg (1993). Migraine related seizures in adults with epilepsy, with EEC correlation. Neurology 43:2476 – 2483.
- Merikangas, K.R. (1990). Genetic epidemiology of migraine. In Migraine: A Spectrum of Ideas (M. Sandier and G.M. Collins, eds.), pp. 40 – 47. Oxford University Press, Oxford.
- Merikangas, K.R., J. Angst, and H. Isler (1990). Migraine and psychopathology: Results of the Zurich cohort study of young adults. Arch. Gen. Psychiatry 47:849 – 853.
- Merikangas, K.R., J.R. Merikangas, and J. Angst (1993). Headache syndromes and psychiatric disorders: Associations and familial transmission. J. Psychiatr. Res. 27:197 – 210.
- Merikangas, K.R., N.J. Risch, J.R. Merikangas et al. (1988). Migraine and depression: Association and familial transmission. J. Psychiatr. Res. 22: 119 – 129.
- Merikangas, K.R., D.E. Stevens, and J. Angst (1993). Headache and personality: Results of a community sample of young adults. J. Psychiatr. Res. 27:187 – 196.
- Miller, D., D.D. Waters, W. Warnica et al. (1981). Is variant angina the coronary manifestation of a generalized vasospastic disorder. N. Engl. J. Med. 304:763 – 766.
- Morrison, D.P. and W.H. Price (1989). The prevalence of psychiatric disorder among female new referrals to a migraine clinic. Psychol. Med. 19:919 – 925.
- O’Keeffe, S.T., N.P. Tsapatsaris, and W.P. Beetham (1992). Increased prevalence of migraine and chest pain in patients with primary Raynaud disease. Ann. Intern. Med. 116:985 – 989.
- O’Keeffe, S.T., N.P. Tspatsaris, and W.P. Beetham (1993). Association between Raynaud’s phenomenon and migraine in a random population of hospital employees. J. Rheumatol. 20:1187 – 1188.
- Olesen, J. (1993). Synthesis of migraine mechanisms. In The Headaches (J. Olesen, P. Tfelt-Hansen, and K.M.A. Welch, eds.), pp. 247 – 253. Raven Press, New York.
- Ottman, R. and R.B. Lipton (1994). Comorbidity of migraine and epilepsy. Neurology 44:2105 – 2110.
- Ottman, R. and R.B. Lipton (1996). Is the comorbidity of epilepsy and migraine due to a shared genetic susceptibility? Neurology 47: 918 – 924.
- Pal, B., C. Gibson, J. Passmore et al. (1989). A study of headaches and migraine in Sjogren’s syndrome and other rheumatic disorders. Ann. Rheum. Dis. 48:312 – 316.
- Passchier, J., H. Hylkema, and J.F. Orlebeke (1984). Personality and headache type: A controlled study. Headache 24:140 – 146.
- Passchier, J. and J.F. Orlebeke (1985). Headaches and stress in school children: An epidemiological study. Cephalalgia 5:167 – 176.
- Phillips, C. (1976). Headache and personality. J. Psychosom. Res. 20:535 – 542.
- Rasmussen, B.K. (1992). Migraine and tension-type headache in a general population: Psychosocial factors. Int. J. Epidemiol. 21:1138 – 1143.
- Rothrock, J., J. North, K. Madden et al. (1993). Migraine and migrainous stroke: Risk factors and prognosis. Neurology 43:2473 – 2476.
- Schmidt, F.N., P. Carney, and G. Fitzsimmons (1986). An empirical assessment of the migraine personality type. Psychosom. Res. 30:189 – 197.
- Shechter, A., W.F. Stewart, and D.D. Celentano (1990). An epidemiologic study of migraine and head injury [Abstract]. Neurology 40:245.
- Silberstein, S.D., R.B. Lipton, and N. Breslau (1995). Migraine: Association with personality characteristics and psychopathology. Cephalalgia 15:337 – 369.
- Sternbach, R.A. (1980). MMPI pattern in common headache disorders. Headache 20:311 – 315.
- Stewart, W.F., M.S. Linet, and D.D. Celentano (1989). Migraine headaches and panic attacks. Psychosom. Med. 51:559 – 569.
- Stewart, W.F., M.S. Linet, D.D. Celentano et al.(1991). Age and sex-specific incidence rates of migraine with and without visual aura. Am. J. Epidemiol. 34:1111 – 1120.
- Stewart, W.F., A. Shechter, and J. Liberman.(1992). Physician consultation for headache pain and history of panic: Results from a population-based study. Am. J. Med. 92:35S – 40S.
- Tatemichi, T.K. and J.P. Mohr (1986). Migraine and stroke. In Stroke: Pathophysiology, Diagnosis and Management (H.J.M. Barnett, B.M. Stein, J.P. Mohr et al., eds.), pp. 845 – 863. Churchill Livingstone, New York.
- Terwindt, G.M., J. Haan, R.A. Ophoff et al.(2000). Clinical and genetic analysis of a large Dutch family with autosomal dominant vascular retinopathy, migraine, and Raynaud’s phenomenon. Brain 121:303 – 316.
- Touraine, G.A. and G. Draper (1934). The migrainous patient: A constitutional study. J. Nerv. Ment. Dis. 80:183 – 204.
- Tzourio, C., S.J. Kittner, M.G. Bousser et al.(2000). Migraine and stroke in young women. Cephalalgia 20:190 – 199.
- Tzourio, C., A. Tehindrazanarivelo (1993). Case-control study of migraine and risk of ischemic stroke. BMJ 307:289 – 292.
- Tzourio, C., A. Tehindrazanarivelo, S. Iglesias et al. (1995). Case-control study of migraine and risk of ischemic stroke in young women. BMJ 310:830 – 833.
- Weber, R.B. and O.M. Reinmuth (1972). The treatment of migraine with propranolol. Neurology 22:366 – 369.
- Weeks, R., S. Baskin, and F. Sheftell (1983). A comparison of MMPI personality data and frontalis electromyographic readings in migraine and combination headache patients. Headache 23:75 – 82.
- Welch, K.M.A. (1987). Migraine: A behavioral disorder. Arch. Neurol. 44:323 – 327.
- Welch, K.M.A. (1994). Relationships of stroke and migraine. Neurology 44:33 – 36.
- Welch, K.M.A., G.L. Barkley, N. Tepley et al.(1991). Magnetoencephalographic studies of migraine: Evidence for central neuronal hyperexcitability. In New Advances in Headache Research (F.C. Rose, ed.), pp. 127 – 130. Smith Gordon, London.
- Welch, K.M.A., E. Chabi, J.H. Nell et al. (1976). Biochemical comparison of migraine and stroke. Headache 6:160.
- Winkler, G.J. and R.R. Young (1974). Efficacy of chronic propranolol therapy in action tremors of the familial, senile, or essential varieties. IV. Engl. J. Med. 290:984 – 988.
- Wolff, H.G. (1937). Personality features and reactions of subjects with migraine. Arch. Neurol. Psychiatry 37:895 – 921.
- Zahavi, I., A. Chagnac, R. Hering et al. (1984). Prevalence of Raynaud’s phenomenon in patients with migraine. Arch. Intern. Med. 144: 742 – 744.
Aaron L Shechter
Richard B Lipton
Stephen D Silberstein
Editors: Silberstein, Stephen D.; Lipton, Richard B.; Dalessio, Donald J.