INTRODUCTION — The relationship between headache, migraine, and stroke is complex. They are common conditions that can coexist independently, as associated risk factors, or by causal relationship. Possible relationships between these entities include:
●Headache may be coincidental with stroke (see 'Headache coincidental with stroke' below)
●Stroke may be the cause of a headache (see 'Headache due to stroke and other cerebrovascular conditions' below)
●Migraine may be the cause of a stroke (see 'Stroke due to migraine headache' below)
●Migraine and other forms of headache may be a risk factor for stroke (see 'Migraine as a risk factor for stroke' below and 'Nonspecific headache and stroke risk' below)
In addition, some forms of migraine headache may have clinical features of stroke, and some cerebrovascular events can have clinical features of migraine. (See 'Stroke and migraine mimics' below and "Pathophysiology, clinical manifestations, and diagnosis of migraine in adults", section on 'Differential diagnosis' and "Differential diagnosis of transient ischemic attack and acute stroke", section on 'Migraine aura'.)
Future modifications are likely, as knowledge of the epidemiology and pathophysiology of these relationships advances.
EPIDEMIOLOGY — Headache, migraine, and stroke are all common conditions. The epidemiology of the intersection of migraine and stroke can be examined by the prevalence of migraine in stroke patients and the incidence of stroke in patients with migraine.
The epidemiology of ischemic and hemorrhagic stroke and common headache disorders is reviewed separately.
●(See "Stroke: Etiology, classification, and epidemiology", section on 'Epidemiology'.)
Prevalence of migraine in stroke — Data on the prevalence of migraine in stroke patients vary in different retrospective studies. A small case-control study of 145 patients in France reported that the prevalence of migraine among patients with ischemic stroke was double that of controls (60 versus 30 percent) [1]. In a European World Health Organization (WHO) collaborative study, the prevalence of migraine in patients with all types of stroke compared with controls was 25 versus 13 percent [2]. However, this study has been criticized on several grounds, including the high proportion of migraine with aura patients compared with those without aura and the high incidence of migrainous stroke (between 20 to 40 percent) among the study participants, a finding that does not concur with clinical experience [3].
Prevalence rates between 27 and 34 percent have been reported in cohorts of younger adults with stroke. The Collaborative Group for the Study of Stroke in Young Women found that the prevalence of migraine in females with stroke, hospitalized controls, and controls was 34, 33, and 24 percent, respectively [4]. In a case-control study of 1668 adults <45 years old with cryptogenic stroke, the prevalence of migraine was 27 percent for cases compared with 17 percent for matched controls [5]. The applicability of these data to older patients is uncertain. Younger patients have higher baseline prevalence of migraine and lower burden of stroke risks than older patients.
Incidence of stroke in migraine — The true incidence of stroke in migraine is unknown due to varied criteria used to identify patients with migraine and reporting bias. In a Taiwanese case-control study involving nearly 2400,000 patients, the risk of ischemic stroke over a median of 3.6 year interval was higher for patients with a history of migraine than those without (adjusted hazard ratio 1.24, 95% CI, 1.1-1.4) [6].
The incidence of stroke due to migraine (migrainous stroke) ranges from 0.8 to 3.4 per 100,000 per year [7,8]. In a study that used a strict definition of migrainous infarction, migraine-induced stroke accounted for 13.7 percent of infarcts in young adults [9]. Case series and stroke registries have reported migrainous infarction accounts for an estimated 0.2 to 0.8 percent of all ischemic strokes [7,9-12].
HEADACHE COINCIDENTAL WITH STROKE — Headache or migraine may occur coincidentally with stroke since both are common conditions. With advancing age, the prevalence of migraine decreases, while that of stroke increases. In addition, stroke risk factors such as hypertension, diabetes, and heart disease are more common in older age groups.
Migraine and stroke may occur together as presenting features of or covariables for other conditions such as antiphospholipid antibody syndrome. (See 'Interaction of migraine with other stroke risk factors' below.)
HEADACHE DUE TO STROKE AND OTHER CEREBROVASCULAR CONDITIONS
Intracranial hemorrhage — Headache at or near the onset of stroke occurs almost invariably in subarachnoid hemorrhage (SAH) [13]. A premonitory or sentinel headache may occur before SAH in 10 to 43 percent of patients due to aneurysm rupture [14]. Therefore, sentinel headache is important to recognize because it may signal an aneurysmal leak days or weeks before a more devastating SAH. (See "Aneurysmal subarachnoid hemorrhage: Clinical manifestations and diagnosis", section on 'Clinical presentation'.)
For patients with intracerebral hemorrhage (ICH), headache may occur acutely at stroke onset, or may occur within hours of onset as the hematoma gradually expands and begins to compress pain sensitive intracranial structures such as larger arteries and the meninges. In some cases of ICH, headache may not be present at all. (See "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and diagnosis", section on 'Clinical presentation'.)
Ischemic stroke — For patients with ischemic stroke of large vessel origin, headache may occur prior to, during, or after stroke onset [15]. In one prospective study of 284 patients with acute ischemic stroke, concomitant headache during the early phase of stroke was reported by 38 percent [16]. Although the cause is often unclear, several plausible mechanisms have been postulated, including vascular dilation as a homeostatic response to ischemia and direct arterial irritation by thrombus, embolism, or dissection [17]. Headache may be common with specific ischemic stroke presentations and causes, including the following:
●Cervical internal carotid artery dissection – Cervical internal carotid artery dissection may occasionally present with isolated headache or as a migraine mimic with visual scintillating scotomata [18,19]. One study of 161 patients found that nearly 70 percent of cervical carotid and vertebral dissections were associated with headache, and headache was the initial symptom in 33 to 47 percent [20]. Another study found that 19 of 21 patients with angiographically documented carotid dissection had ipsilateral head pain in one or more regions such as the orbit, frontal region, and side of the head [21]. The head pain was typically acute and severe, and neck pain occurred as well in 12 patients. About three quarters of the 21 patients had ischemic events related to the dissection, with the headache preceding the ischemic symptoms in about half.
The relationship of dissection with headache is further complicated because approximately half of patients with cervical artery dissection also have a prior history of migraine. (See 'Interaction of migraine with other stroke risk factors' below.)
●Insular cortex infarction – Ischemic stroke involving the insula may present with headache [22]. One study using magnetic resonance imaging (MRI) lesion mapping found that infarctions in the insular cortex were significantly associated with headache, perhaps related to the role of this region in pain processing [23]. Headache is uncommon in subcortical small vessel stroke syndromes. (See "Clinical diagnosis of stroke subtypes" and "Overview of the evaluation of stroke".)
●Posterior circulation infarction – Multiple observational studies have reported an association between headache and acute ischemic stroke involving the posterior arterial circulation [22,24-26]. A meta-analysis of observational studies of adults with ischemic stroke found the prevalence of headache for patients with posterior circulation stroke was nearly twice that of patients with anterior circulation stroke (odds ratio [OR] 1.9, 95% CI 1.4-2.6) [27].
Migraine has also been associated with the presence of asymptomatic stroke-like lesions in the posterior circulation on brain MRI in patients without a clinical history of stroke. (See 'Subclinical brain lesions' below.)
Reversible cerebral vasoconstriction syndromes — Reversible cerebral vasoconstriction syndrome (RCVS) is a group of conditions characterized by reversible narrowing and dilatation of the cerebral arteries. The clinical presentation of RCVS is usually dramatic with sudden, severe "thunderclap" headaches that simulate aneurysmal SAH; however, in patients with RCVS, thunderclap headaches often recur over a span of one to four weeks. The etiology of RCVS is unknown, though the reversible nature of the vasoconstriction suggests an abnormality in the control of cerebrovascular tone.
Recurrence of an episode of RCVS is rare, but some patients develop chronic headaches after RCVS, which are usually migrainous in nature.
RCVS is discussed in greater detail separately. (See "Reversible cerebral vasoconstriction syndrome".)
Others — Headache may also be a presenting feature of other cerebrovascular conditions. These conditions share a common pathophysiology involving failure of cerebral blood flow autoregulation or endothelial dysfunction [28].
●Reversible posterior leukoencephalopathy syndrome [29] (see "Reversible posterior leukoencephalopathy syndrome")
●Hypertensive encephalopathy [28,30] (see "Moderate to severe hypertensive retinopathy and hypertensive encephalopathy in adults")
●Cerebral hyperperfusion syndrome [31] (see "Complications of carotid endarterectomy", section on 'Hyperperfusion syndrome')
●Stroke-like migraine attacks after radiation therapy (SMART) [32] (see "Delayed complications of cranial irradiation", section on 'Migraine-like headache (SMART) syndrome')
●Cerebral arteriovenous malformation (AVM) [33,34] (see "Brain arteriovenous malformations", section on 'Clinical presentation')
●Moyamoya disease and syndrome [35] (see "Moyamoya disease and moyamoya syndrome: Etiology, clinical features, and diagnosis", section on 'Other manifestations')
●Vasculitis involving the central nervous system (both primary and systemic) [36-39] (see "Primary angiitis of the central nervous system in adults" and "Overview of and approach to the vasculitides in adults")
●Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) [40,41] (see "Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)", section on 'Migraine with aura')
Some of these conditions may present with headaches that have migrainous features. Patients with cerebral AVMs may present with migraine-like attacks that lateralize to the same cerebral hemisphere [33,34,42]. Migraine-like headaches are a frequent and early manifestation of both SMART syndrome and CADASIL and may be the sole symptom in some patients.
STROKE DUE TO MIGRAINE HEADACHE — Ischemic stroke may occur as a complication of severe migraine, typically migraine with aura. However, it can be difficult to determine migraine as the cause of stroke; experts vary in defining migraine-associated stroke [3,43-48].
Prolonged or severe changes in cerebral blood flow have been frequently postulated as the cause of migrainous infarction. However, this assumption has been challenged by the limited supportive data and competing nonvascular causes to migraine that may cause or contribute to the risk of stroke. (See 'Mechanisms' below.)
Diagnostic criteria
Migrainous infarction — The International Classification of Headache Disorders, 3rd edition (ICHD-3) defines migrainous infarction by the following features [48]:
●(A) A migraine attack fulfilling criteria B and C
●(B) Occurring in a patient with migraine with aura and typical of previous attacks except that one or more aura symptoms persists for >60 minutes
●(C) Neuroimaging demonstrates ischemic infarction in a relevant area
●(D) Not better accounted for by another diagnosis
Migrainous infarction also may be called migraine-induced stroke [3].
Migraine-related stroke — Some experts have used the term migraine-related stroke to expand the definition of migrainous infarction and allow inclusion of patients who have migraine without aura [46]. Others use migraine-related stroke for cases when additional stroke mechanisms coexist with migraine [47].
Since the 1990s, when migraine was thought to have only vascular pathophysiology, several reports have noted the occurrence of migrainous infarction associated with attacks of migraine without aura [43-45]. However, most studies have found no association of migraine without aura and ischemic stroke [48,49].
Clinical and imaging findings — There are limited data on patients with acute migrainous infarction who have had a complete stroke evaluation. The largest study with modern neuroimaging is a case series of 11 patients with migrainous infarction according to strict criteria who were identified from a stroke database of 8137 patients [50]. All patients reported symptoms at onset similar to previous migraine aura without new or atypical symptoms. However, the previously transient aura symptoms persisted. On diffusion-weighted brain MRI sequences, 4 of the 11 patients had multiple foci of acute infarction, mainly in the posterior circulation, while four each had a single area of acute infarction in the posterior circulation territory, and three had isolated infarcts in the middle cerebral artery territory (image 1).
MIGRAINE AS A RISK FACTOR FOR STROKE
Ischemic stroke — Evidence from multiple meta-analyses supports an association between migraine, particularly migraine with aura, and ischemic stroke risk [51-54], including an association with cryptogenic stroke and transient ischemic attack (TIA) [5,55]. In a case-control study of 347 adults age <50 years with stroke and age- and sex-matched controls, migraine with aura was associated with cryptogenic ischemic stroke (odds ratio [OR] 3.5, 95% CI 2.2-5.6) [49]. An association was not found for patients with migraine without aura. The absolute increase in the risk of stroke due to migraine with aura appears to be small [51,56].
Magnitude and modifiers of risk — Evidence supporting migraine as an independent risk factor for ischemic stroke comes from a meta-analysis that included 25 studies (13 case-control, 10 cohort, and 2 cross-sectional) published through January 2009 [51]. The strength of this meta-analysis is limited mainly by the case-control nature of many of the studies, with their inherent susceptibility to recall bias. In addition, the included studies were heterogeneous with regard to subject characteristics and cardiovascular disease definitions. In nine studies, the pooled relative risk (RR) for ischemic stroke among subjects with any type of migraine was 1.73 (95% CI 1.31-2.29). In studies with available data stratification, the risk of ischemic stroke was significantly increased for the following subgroups [51]:
●Females with migraine with aura (pooled RR 2.08, 95% CI 1.13-3.84) but not males (pooled RR 1.37, 95% CI 0.89-2.11)
●Subjects with migraine <45 years of age (pooled RR 2.65, 95% CI 1.41-4.97)
●Subjects who smoke and had migraine with aura (pooled RR 9, 95% CI 4.2-19.3)
●Females currently using oral contraceptives who had migraine with aura (pooled RR 7, 95% CI 1.5-32.7)
Similar clinical factors have been reported in other studies [6,57]. In a study of nearly 120,000 patients in Taiwan that compared patients with migraine and a propensity score-matched comparison cohort, migraine was associated with an increased risk of ischemic stroke (adjusted hazard ratio [aHR] 1.2, 95% CI 1.1-1.4) [6]. In subgroup analyses, the highest risk was reported in females aged ≤45 years who had migraine with aura (aHR 4.6, 95% CI 2.5-8.6).
The relationship between migraine and stroke risk may vary by life course of migraine. While migraine may confer a risk for stroke, active migraine headaches may attenuate this risk and indicate a healthy vascular system. In an analysis of patients from the Women’s Health Study stratifying patients by present versus past history of migraine, females age ≥45 years old with an elevated risk of future cardiovascular disease were likelier to have a history of migraine than those with a low risk of future cardiovascular disease but less likely to have an active history of migraine (odds ratio 0.64, 95% CI 0.5-0.8) [58].
Mechanisms — The pathophysiology underlying migraine as a risk factor or cause for stroke is not clear. Multiple cerebral, vascular, hematologic, and cardiac mechanisms have been suggested, including the following:
●Cerebral and neuronal factors
•Prolongation of cortical spreading depression (CSD) and aura [59]
•Neuronal glutamatergic hyperexcitability resulting in enhanced susceptibility to ischemic depolarizations [60,61]
•Dysregulated activity of serotonergic raphe cells causing excitotoxicity [62]
●Vascular factors
•Vasospasm and changes in cerebral blood flow [3,46,63-66]
•Release of prothrombotic factors or vasoactive peptides [67-72]
•Endothelial dysfunction [61,73]
●Prothrombotic factors
•Increased platelet aggregability [74-76]
•Elevated von Willebrand factor [71]
•Higher prevalence of hypercoagulable states [77]
•Prothrombotic genetic polymorphisms (eg, the methylenetetrahydrofolate reductase C677T variant) [78] (See "Overview of homocysteine", section on 'Disease associations'.)
●Cardiac factors
•Atrial fibrillation attributed to the autonomic dysfunction associated with migraine [79,80]
•Myocardial infarction associated with migraine leading to cardioembolism [81-85]
None of the postulated mechanisms has been confirmed as a pathophysiological explanation linking stroke and migraine. However, posterior circulation border zone infarcts in migraine have been most frequently attributed to a combination of low flow (hypoperfusion) and local thromboembolism [86,87].
The pathophysiology of migraine is discussed in greater detail separately. (See "Pathophysiology, clinical manifestations, and diagnosis of migraine in adults", section on 'Pathophysiology'.)
The impact of migraine aura — The increased risk of stroke appears to be driven largely from subjects who had migraine with aura [51,52,54,59]. In one meta-analysis of 16 cohort studies involving more than 1.1 million patients, migraine was associated with an elevated risk of stroke (aHR 1.4, 95% CI 1.3-1.6) [54]. When stratified by migraine subtype, the risk was elevated for patients with migraine with aura (aHR 1.6, 95% CI 1.3-1.9) but not those with migraine without aura (aHR 1.1, 95% CI 0.9-1.3). In an analysis of more than 27,000 female health professionals from the Women’s Health Study cohort, the adjusted incidence rate of major cardiovascular events was 3.36 per 1000 person-years (95% CI 2.72-3.99) for those with migraine with aura and 2.11 per 1000 person-years (95% CI 1.98-2.24) for those with migraine without aura or no migraine history [88].
Migraine with and without aura may be associated with an elevated perioperative stroke risk, although the risk appears to be higher for those with migraine with aura. In a prospective hospital registry of nearly 125,000 surgical patients, the risk of perioperative ischemic stroke was elevated for patients with and without aura but higher for patients with a history of migraine with aura (adjusted OR [aOR] 2.61, 95% CI 1.6-4.3) than those with migraine without aura (aOR 1.6, 95% CI 1.3-2.1) [89].
The role of sex — There is evidence that females who have migraine are at increased risk of ischemic stroke [51,88,90], but the absolute increase in the risk of stroke is small [91]. Smoking, estrogen-progestin contraceptive use, aura, and age <45 years appear to confer additional risk in these patients [51]. (See 'Magnitude and modifiers of risk' above and 'The impact of migraine aura' above.)
However, none of the relevant studies of migraine and stroke risk have distinguished whether the estrogen content of the estrogen-progestin contraceptives was high or low [92], which other reports have identified as a critical factor related to stroke risk. (See "Combined estrogen-progestin contraception: Side effects and health concerns", section on 'Myocardial infarction and stroke'.)
Intracerebral hemorrhage — Most studies have reported on the association between migraine and ischemic stroke. However, migraine has been identified as a possible risk factor for other cerebrovascular conditions, including intracerebral hemorrhage [85]. The relationship of migraine with intracerebral hemorrhage is supported by a meta-analysis of eight studies (four case-control and four cohort), which found that the overall pooled effect estimate of hemorrhagic stroke was 1.48 (95% CI 1.16-1.88) for subjects with any migraine [93].
Subclinical brain lesions — Several prospective population-based studies have found an association between migraine with aura and silent infarct-like lesions on brain MRI [10,86,94-96]. However, the etiology, nature, and clinical significance of the MRI lesions reported in these studies remains unclear [96,97].
A population-based long-term study of 4689 subjects from Iceland evaluated at a mean age of 51 years and then reevaluated at a mean age of 76 years by interview and brain MRI; subjects who had migraine with aura at the initial evaluation had an increased risk of infarct-like lesions 25 years later (aOR 1.4, 95% CI 1.1-1.8) [95]. This result was driven mainly by an increased risk of cerebellar infarct-like lesions in the subgroup of females who had migraine with aura (OR 1.9, 95% CI 1.4-2.6). Migraine with (but not without) aura was also associated with an increased risk for subclinical posterior circulation territory infarct-like lesions in a cross-sectional study of Dutch adults aged 30 to 60 years [94]. Most lesions were in the cerebellum. In another study report, patients with migraine had a significantly increased prevalence of small infratentorial hyperintense lesions, most located in the mid-pons [98].
A 2013 systematic review and meta-analysis of four clinic-based case-control studies found that white matter lesions were more common in subjects with migraine compared with controls [96]. The association was significant for migraine with aura (OR 1.68, 95% CI 1.07-2.65) but not for migraine without aura (OR 1.34, 95% CI 0.96-1.87). By contrast, a subsequent population-based study found that severe white matter disease was associated with migraine without aura (OR 1.87, 95% CI 1.04-3.37) but migraine with aura was not (OR 0.55, 95% CI 0.17-1.83) [99]. In this study, a history of migraine was not associated with white matter lesion progression over time [99].
Interaction of migraine with other stroke risk factors — Migraine has been associated with other known or putative risk factors for stroke, including:
●Patent foramen ovale (PFO) [100] (see "Pathophysiology, clinical manifestations, and diagnosis of migraine in adults", section on 'Right-to-left cardiac shunt' and "Atrial septal abnormalities (PFO, ASD, and ASA) and risk of cerebral emboli in adults")
●Cervical artery dissection [101] (see "Cerebral and cervical artery dissection: Clinical features and diagnosis", section on 'Associated conditions and risk factors')
●Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) [102] (see "Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)", section on 'Migraine with aura')
●Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like symptoms (MELAS) [103] (see "Mitochondrial myopathies: Clinical features and diagnosis", section on 'MELAS')
●Antiphospholipid antibodies and lupus [104-107] (see "Clinical manifestations of antiphospholipid syndrome", section on 'Neurologic involvement')
●Livedo reticularis and Sneddon syndrome [108-111]
●Sickle cell disease [112] (see "Overview of the clinical manifestations of sickle cell disease", section on 'Neurologic complications')
●Cardiovascular disease including myocardial infarction [81-85]
NONSPECIFIC HEADACHE AND STROKE RISK — Nonmigrainous headache may be a predictor of ischemic stroke risk, but the evidence is conflicting. The United States National Health and Nutrition Examination Survey involved more than 14,000 participants who were followed for 10 years [113]. The study found a significant association of stroke with severe nonspecific headache in both females and males. Among participants younger than 45 years of age, there was a fivefold increase in stroke in the headache group compared with those in the no-headache group (3.6 versus 0.7 percent for males; 2.2 versus 0.4 percent for females). The risk of stroke related to headache was lower in older patients, presumably due to higher prevalence of other cerebrovascular risk factors and reduced prevalence of headache with increasing age. However, other cohorts have reported an elevated risk of stroke in older patients with nonmigrainous headaches [114].
In a prospective cohort study of 35,056 Finnish subjects, males with chronic, unspecified headache had a fourfold higher risk of stroke during the first 12 months of follow-up as compared with those without headache [115]. The nonspecific headache associated hazard ratio of stroke for males decreased for each interval of follow-up from 4.1 (95% CI 2.1-7.93) at one year to 1.86 at five years and 1.2 at 23 years. In the same study, an association between chronic headache and the risk of stroke was not found in females, perhaps due to the higher prevalence and more heterogeneous etiology of nonspecific headaches in females [115].
Other studies have failed to identify an association between nonmigrainous headache and stroke. The Physician's Health Study did not find an association between nonmigraine headache and subsequent stroke in males [116]. Similarly, the Women's Health study reported that headache in general and nonmigraine headache were not associated with stroke risk in females [117].
STROKE AND MIGRAINE MIMICS — Both cerebrovascular events and migraines can present as acute transient neurologic events with similar symptoms. In addition, acute neurologic symptoms that are persistent may also be caused by either migraine or stroke.
Migraine headache mimicking stroke — Migraine with aura occurs in about 15 to 20 percent or more of patients with migraine and may mimic stroke [118].
●Typical aura – Typical migraine aura symptoms develop gradually over 5 to 20 minutes and last less than one hour per symptom; the most common types involve homonymous visual disturbances. Other common types of migraine aura may manifest as sensory, motor, brainstem, or language disturbances. There is usually little clinical difficulty recognizing these auras as manifestations of migraine when the auras are brief and precede headaches. In addition, migraine aura is typically characterized by positive symptoms (eg, presence of bright lights or visual aberrations) while stroke symptoms typically involve loss of function or negative symptoms (eg, vision loss). (See "Pathophysiology, clinical manifestations, and diagnosis of migraine in adults", section on 'Migraine aura'.)
●Other forms of migraine – Some forms of migraine present with motor or brainstem symptoms that may mimic transient ischemic attack (TIA) or acute stroke. These include:
•Sporadic and familial hemiplegic migraine (see "Hemiplegic migraine")
•Migraine with brainstem aura (see "Migraine with brainstem aura")
•Retinal or ocular migraine (see "Pathophysiology, clinical manifestations, and diagnosis of migraine in adults", section on 'Retinal migraine')
Hemiplegic and brainstem auras may also be prolonged, requiring neuroimaging evaluation to distinguish from acute stroke.
●Migraine aura without headache – Migraine aura that occurs without headache may be difficult to distinguish from stroke symptoms. This form of migraine was previously known as acephalgic migraine, and migraine with acute-onset aura. These symptoms are more common in patients over age 50 years and may also be called late-life migraine accompaniments [119]. (See "Pathophysiology, clinical manifestations, and diagnosis of migraine in adults", section on 'Migraine aura'.)
●Persistent aura without infarction – Prolonged or atypical auras may be difficult to distinguish from TIA or acute stroke. Prolonged symptoms may last for the entire headache, for several days or weeks, or in some cases leave a permanent neurologic deficit. Many such patients have neuroimaging evidence of acute stroke, indicating migrainous infarction. However, some patients have persistent aura without infarction if the aura lasts one week or longer with no evidence of infarction. (See "Pathophysiology, clinical manifestations, and diagnosis of migraine in adults", section on 'Complications of migraine'.)
Stroke mimicking migraine or other headaches — Some patients with ischemic or hemorrhagic cerebrovascular conditions may present with isolated headache without associated focal neurologic impairment, such as weakness, numbness, aphasia, or visual dysfunction [3]. Specific stroke symptoms vary according to the brain regions impacted and some small cerebrovascular lesions may not produce neurologic deficits. Headache may occur due to activation of nociceptors in vascular walls from acute thrombosis or those in dural membranes from local mass effect of bleeding or edema. Cerebrovascular conditions that may commonly present with isolated headache include:
●Subarachnoid hemorrhage – Aneurysmal subarachnoid hemorrhage (SAH) frequently presents with acute onset (thunderclap) severe headache. Other patients may present with a prodrome or less severe headaches, frequently called "sentinel headaches" up to several days prior to overt SAH. (See "Aneurysmal subarachnoid hemorrhage: Clinical manifestations and diagnosis", section on 'Clinical presentation'.)
●Cerebral venous thrombosis – Headache is the most common clinical feature of cerebral venous thrombosis (CVT) being present in nearly 90 percent of patients [120]. Headache characteristics in CVT may be focal or diffuse and can mimic migraine but are frequently gradually progressive. (See "Cerebral venous thrombosis: Etiology, clinical features, and diagnosis", section on 'Headache'.)
●Subdural and epidural hematomas – Acute intracranial bleeding in the potential spaces adjacent to the nociceptor-containing dural membranes can present with acute or chronic headaches. Epidural hematomas may present with headache due to bleeding between the dura and inner table of the skull, but additional neurologic deficits from mass effect on the underlying brain tissue are common, such as hemiparesis or impaired consciousness. Similarly, subdural hematomas (SDH), due to bleeding between the dura and arachnoid membranes, can present with headache with or without other neurologic deficits. Patients with chronic SDH are likelier to present with nonfocal symptoms such as isolated headache, but symptoms may be progressive if the bleeding expands. (See "Intracranial epidural hematoma in adults" and "Subdural hematoma in adults: Etiology, clinical features, and diagnosis".)
●Intracerebral hemorrhage – Large volume intracerebral hemorrhages may present with headache that is typically associated with nausea and/or vomiting and a decreased level of consciousness due to mass effect of the bleeding and brain compression. (See "Spontaneous intracerebral hemorrhage: Pathogenesis, clinical features, and diagnosis", section on 'Clinical presentation'.)
●Ischemic stroke – Headache can occasionally occur with TIA or ischemic stroke due to acute arterial thromboembolism. Headache due to cerebral edema in large ischemic strokes is typically associated with additional neurologic deficits. (See "Clinical diagnosis of stroke subtypes", section on 'Associated symptoms'.)
STROKE PREVENTION FOR PATIENTS WITH MIGRAINE — Treatment aimed at primary or secondary stroke prevention in patients with migraine or nonspecific headache is not well studied, but an approach combining stroke risk factor control with migraine prophylaxis seems most reasonable.
Preventive therapy for stroke and treatment of migraine are discussed separately.
●(See "Overview of primary prevention of cardiovascular disease".)
●(See "Overview of secondary prevention of ischemic stroke".)
●(See "Acute treatment of migraine in adults".)
●(See "Preventive treatment of episodic migraine in adults".)
General approach — The overall approach to the preventive stroke treatment of patients with migraine is similar to other patients without migraine. Patients with additional stroke risk factors such as hypertension, tobacco use, or high-estrogen-containing oral contraception, should be informed about the increased stroke risk and efforts should be taken to minimize risks. (See "Overview of secondary prevention of ischemic stroke".)
Patients with migraine should be taught to recognize the early warning signs of stroke to prevent confusion between migraine aura and transient ischemic attack (TIA) (table 1) and to seek appropriate intervention. Similarly, clinicians should be aware of the potentially increased risk of stroke in the migraine population and should not dismiss focal symptoms in their evaluation of these patients. (See "Differential diagnosis of transient ischemic attack and acute stroke", section on 'Distinguishing transient attacks'.)
Antithrombotic therapy — Primary prevention of stroke with aspirin or other antiplatelet therapy is not warranted for patients with migraine with or without aura in the absence of cardiovascular risk factors. (See "Aspirin in the primary prevention of cardiovascular disease and cancer", section on 'Assessing benefits and risks'.)
Secondary stroke prevention with antiplatelet or anticoagulant medications is warranted for patients with and without migraine who have a history of TIA or stroke. (See "Overview of secondary prevention of ischemic stroke", section on 'Antithrombotic therapy'.)
Estrogen-containing therapies — Estrogen-containing therapies have been associated with an increased risk of thromboembolism. The use of these agents in patients with migraine or stroke varies by strength of indication, dose and formulation, and individual risk factors.
Hormonal contraception — The decision to start or continue estrogen-containing contraceptive therapy in patients with migraine involves shared decision making after discussing individual risks and benefits of therapy and alternative options. We avoid estrogen-containing options, in agreement with guidelines from the World Health Organization (WHO), for patients with migraine and an elevated risk of stroke including the following [121-123]:
●Migraine with aura
●Age 35 years or older
●Multiple cardiovascular risk factors (eg, hypertension, diabetes mellitus, tobacco use)
●History of thromboembolism
For females younger than 35 years old who have migraine without aura and no other risk factors for stroke and use estrogen-containing oral contraception, we use a low-dose formulation, specified as less than 50 mcg as per the American College of Obstetricians and Gynecologists (ACOG) guidelines or less than 35 mcg as per WHO guidelines [121,122,124]. However, the frequency and severity of their migraines should be monitored [122]. (See "Combined estrogen-progestin contraception: Side effects and health concerns", section on 'Headache and migraine'.)
Estrogen-containing contraception therapy is contraindicated in patients with a history of stroke and those with multiple risk factors for cardiovascular disease [125]. For these patients, we use progestin-only formulations or alternative options for contraception. (See "Contraception: Counseling and selection" and "Progestin-only pills (POPs) for contraception".)
Menopausal hormone therapy — The safety of menopausal hormone therapy in patients with migraine or stroke varies by estrogen dosing and formulation and the overall thromboembolic risk profile.
We avoid hormone replacement therapy for patients with a history of stroke or those at high risk (eg, >10 percent 10-year risk) for cardiovascular disease including stroke (calculator 1). For these patients, we use nonhormonal options that are not associated with an elevated risk of thromboembolic complications. (See "Menopausal hot flashes", section on 'Nonhormonal pharmacotherapy' and "Genitourinary syndrome of menopause (vulvovaginal atrophy): Treatment".)
Migraine is not a contraindication to menopausal hormone therapy. Low-dose estrogen (eg, <50 mcg) is generally felt to be relatively safe in healthy females with migraine. Several studies have failed to find an elevated risk of stroke in females with migraine with aura who are above age 45 years (see 'The role of sex' above). Transdermal formulations may be preferred for patients with menopausal symptoms and estrogen-associated migraines to avoid estrogen-withdrawal headaches that may occur with oral formulations. A task force from the American Headache Society recommends using usual indication, contraindication, and caution while prescribing hormonal replacement therapy to postmenopausal females with migraine with aura [126]. (See "Estrogen-associated migraine, including menstrual migraine", section on 'Peri- and postmenopause'.)
Medications to avoid — Some medications used for acute or preventive treatment of migraine are avoided in those with a history of stroke, TIA, or cardiovascular disease due the risk of cerebral ischemia. These include vasoconstrictive medications:
●Triptans
●Ergotamine derivatives
●Serotonin antagonists (eg, pizotifen and methysergide)
We also avoid long-term use of nonsteroidal antiinflammatory drugs (NSAIDs) in older patients and in patients with other uncontrolled risk factors for stroke due to the elevated risk of thrombotic cardiovascular events [127]. (See "NSAIDs: Adverse cardiovascular effects", section on 'NSAIDs and cardiovascular events'.)
We suggest that beta blockers should not be used as initial therapy for migraine prophylaxis in patients over age 60 years and in patients who smoke. Compared with other antihypertensive drugs in the primary treatment of hypertension, beta blockers may be associated with a higher rate of stroke and other cardiovascular events. (See "Choice of drug therapy in primary (essential) hypertension".)
The safety of calcitonin gene-related peptide antagonists for patients with a history of or uncontrolled risk factors for stroke has not been established [128,129].
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Stroke in adults".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Migraines in adults (The Basics)" and "Patient education: Headaches in adults (The Basics)")
●Beyond the Basics topics (see "Patient education: Headache causes and diagnosis in adults (Beyond the Basics)" and "Patient education: Migraines in adults (Beyond the Basics)" and "Patient education: Headache treatment in adults (Beyond the Basics)" and "Patient education: Stroke symptoms and diagnosis (Beyond the Basics)").
SUMMARY AND RECOMMENDATIONS
●Mechanisms of association – The relationship between headache, migraine, and stroke is complex. They are all common conditions that can coexist independently, by temporal association, or by causal relationship. In addition, some forms of migraine headache may have clinical features of stroke and some cerebrovascular events can have clinical features of migraine. (See 'Introduction' above.)
•Headache coincidental with stroke – Headache or migraine may occur coincidentally with stroke since both are common conditions. With advancing age, the prevalence of migraine decreases, while that of stroke increases. Migraine and stroke may also occur together as covariables for other conditions. (See 'Headache coincidental with stroke' above.)
•Headache due to stroke – Headache may be a presenting feature of several cerebrovascular conditions. Thunderclap headache almost invariably occurs near the onset of subarachnoid hemorrhage (SAH). Headache may occur prior to, during, or after onset of ischemic stroke and typically occurs as recurrent episodes of thunderclap headache in reversible cerebral vasoconstriction syndrome (RCVS). (See 'Headache due to stroke and other cerebrovascular conditions' above.)
•Stroke due to migraine headache – Ischemic stroke may occur as a complication of severe migraine with aura. Migrainous infarction may also be called migraine-related stroke when due to migraine without aura. (See 'Stroke due to migraine headache' above.)
•Migraine as risk factor for stroke – Migraine headache is a risk factor for stroke due to cerebral, vascular, hematologic, and cardiac possible mechanisms. Migraine may be associated with an elevated risk of ischemic stroke and intracerebral hemorrhage. (See 'Migraine as a risk factor for stroke' above.)
Clinical factors associated with an elevated risk of stroke in patients with migraine include (see 'Magnitude and modifiers of risk' above):
-patients with migraine with aura
-female patients
-patients age <45 years
•Stroke and migraine mimics – Both cerebrovascular events and migraines can present as acute transient neurologic events. In addition, acute neurologic symptoms that are persistent may be caused by either migraine or stroke. (See 'Stroke and migraine mimics' above.)
●Stroke prevention for patients with migraine – Treatment aimed at primary or secondary stroke prevention in patients with migraine or nonspecific headache combines stroke risk factor control with migraine prophylaxis. (See 'Stroke prevention for patients with migraine' above.)
•Antithrombotic therapy – Primary prevention of stroke with aspirin is not warranted for patients with migraine with or without aura in the absence of cardiovascular risk factors. Secondary stroke prevention with antiplatelet or anticoagulant medications is warranted for patients with and without migraine who have a history of transient ischemic attack (TIA) or stroke. (See 'Antithrombotic therapy' above.)
•Estrogen-containing therapies – Estrogen-containing therapies have been associated with an increased risk of thromboembolism. The use of these agents in patients with migraine or stroke varies by strength of indication, dose and formulation, and individual risk factors. (See 'Estrogen-containing therapies' above.)
-Hormonal contraception – We avoid estrogen-containing options for patients with migraine and elevated risk of stroke. For other female patients age <35 years with migraine without aura and no other risk factors for stroke who use estrogen-containing contraception, we prefer oral contraception with low-dose estrogen (eg, <50 mcg). (See 'Hormonal contraception' above.)
-Menopausal hormone therapy – Menopausal hormone therapy with low-dose estrogen (<50 mcg) is generally felt to be relatively safe in healthy females with migraine. We avoid hormone replacement therapy for patients with a history of stroke or those at high risk (eg, >10 percent 10-year risk) for cardiovascular disease including stroke (calculator 1). (See 'Menopausal hormone therapy' above.)
•Medications to avoid – We avoid triptans, ergotamine derivatives, serotonin-antagonists, and long-term use of nonsteroidal antiinflammatory drugs. We do not use beta blockers for patients over age 60 years and those who smoke. (See 'Medications to avoid' above.)
