Both migraine and stroke are chronic neurologic disorders associated with focal neurologic deficits, alterations in cerebral blood flow, and headache. The relationships between migraine and stroke are complex. Headaches have been associated with stroke as ictal, preictal, or postictal phenomena (Welch, 1994). The association between migraine and stroke is strongest for migraine with aura and for stroke within the posterior circulation (Tatemichi and Mohr, 1986; Bougousslavsky and Reglli, 1987; Rothrock et al., 1993). Migraine aura, if sufficiently prolonged, may give rise to stroke, a condition that is termed “true migrainous infarction” (Headache Classification Committee of the International Headache Society, 1988; Welch, 1994).
A number of hospital case series have estimated the proportion of strokes attributable to migraine using case-by-case clinical review. In adult patients under 50 years of age, 1% to 17% of strokes have been attributed to migraine (Welch, 1994; Alvarez et al., 1989; Tatemichi and Mohr, 1986). Bougousslavsky et al. (1987) reported that if stroke occurred during a migraine attack, only 9% of patients had an arterial lesion; if the stroke was remote from the migraine attack, 91% had an arterial lesion. Mechanisms other than traditional arterial disease may underlie migrainous infarction.
A number of case-control studies have examined migraine as a risk factor for stroke. The Collaborative Group for the Study of Stroke in Young Women (1975) compared hospitalized stroke patients with both hospital-based and community controls. There was a twofold increase in the risk of stroke for women with migraine when compared with community controls but not hospital controls (Collaborative Group for the Study of Stroke in Young Women, 1975). Henrich and Horowitz (1989) found an association between migraine and stroke in a hospital-based case-control study, but differences disappeared after adjusting for stroke risk factors.
In case-control studies of young women, patients with stroke were compared to patients without stroke. Four of these studies were hospital-based, with the number of cases varying from 20 to 146 (Batista et al., 1989; Brody and Kadowitz, 1974; Ettinger et al., 1996; Welch et al., 1976). All of the studies showed increased risk of ischemic stroke in migraine patients, with odds ratios (ORs) ranging from 1.9 to 4.3. Tzourio et al. (1993, 1995) reported that migraine was associated with a fourfold increased risk of stroke in women under 45 years of age, with an even greater risk in women who smoked. There was a greater risk among women under 45 years of age who reported a history of migraine with aura. In none of these epidemiologic studies, however, were details available regarding attack, the cause of stroke, or whether the stroke was induced by the migraine attack characteristics. In the largest study, 497 cases were recruited from Danish population-based registries in which all hospitalized cases are registered. Controls were also selected through a national register, and the participation rate was high for both cases and controls (85% and 88%, respectively) (Lindegaard, 1995).
In a longitudinal study, Henrich et al. (1986) estimated that the incidence of cerebral “migrainous infarction” was 3.367 100,000; when subjects with other stroke risk factors were excluded, the estimate decreased to 1.44/100,000. To place this in context, the overall rates of ischemic stroke in the general population under 50 years of age range from 6.5/100,000 to 22.8/100,000 (Kittner et al., 1993). To interpret these data, one must estimate the relative risk (RR) in migraine populations, with and without aura, stratified by migraine type (with and without aura) and adjust for potential confounders.
The association between migraine and hemorrhagic stroke has not been extensively studied. Whereas the Collaborative Group for the Study of Stroke in Young Women (1975) found that migraine was similarly associated with both ischemic and hemorrhagic stroke in the recent European World Health Organization, no association [OR, 1.10, 95% confidence interval (CI) 0.63 – 1.94] with migraine was found (Chang et al., 1999). In the pooled analysis of data from two recent US population-based case-control studies conducted by Kaiser Permanente and the University of Washington, the crude OR was 1.45 (95% CI 1.01 – 2.08). In all three reports, most hemorrhagic stroke cases were subarachnoid hemorrhage (Tzourio et al., 2000).
To better understand the relationship between migraine and stroke, Welch (1994) proposed a classification system that recognizes four types of relationship between migraine and stroke: coexistent stroke and migraine, stroke with clinical features of migraine, migraine-induced stroke, and uncertain classification.
For stroke and migraine to be coexistent, “a clearly defined stroke syndrome must occur remotely in time from a typical migraine attack” (Welch, 1994). It may not be possible to establish the presence or absence of a causal relationship in an individual case. At least some cases may be coincidentally related. Some cases may be linked by underlying risk factors, such as mitral valve prolapse (Gamberini et al., 1984).
In stroke with clinical features of migraine, Welch (1994) indicates that “a structural lesion that is unrelated to migraine pathogenesis presents with clinical features of a migraine attack.” He identifies two subtypes: symptomatic and migraine mimics. In the symptomatic group, an established structural disease causes episodes typical of migraine with aura, an example of which is an arteriovenous malformation that masquerades as migraine. For migraine mimic, stroke is accompanied by headache and other neurologic symptoms and signs that resemble migraine.
In migraine-induced stroke, the neurologic deficit of the stroke must be identical to the neurologic symptoms of prior migraine attacks. In addition, the stroke must occur in the course of a typical migraine attack, and other causes of stroke must be excluded.
When classification is uncertain, migraine and stroke appear to be related, but causal attribution is difficult. For example, a patient may have a typical migraine with aura, take a vasoactive drug such as ergotamine, and then have a cerebral infarction. When this rare sequence occurs, it is not clear if the stroke is a consequence of the migraine itself, of the treatment, or of an interaction between the two factors. To clarify the causal mechanisms, one would need to compare the rates of stroke that occur in close proximity to migraine with aura with and without vasoactive treatment. Migraine-like headaches and stroke may be associated with systemic vasculitis, antiphospholipid antibody syndrome, mitochondrial encepholopathies, and oral contraceptive use. Classifying stroke and migraine in these settings is difficult.
The overall pattern of results is consistent as all studies found an association between migraine and ischemic stroke in women under 45 years of age. However, all of the studies are observational; therefore, the association could be an artifact of some potential bias related to study design. These biases may include patient selection, diagnosis of stroke or migraine, recall bias, or other confounding variables, such as smoking or oral contraceptive use.
- 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.