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Migraine and Stroke


Key Points

  • Migraine and particularly migraine with aura are associated with increased risk of ischemic and hemorrhagic stroke and other vascular events.

  • In few cases does migraine directly result in a stroke.

  • Treatment of stroke in patients with migraine is generally similar to patients without. However, several treatment options to treat or prevent migraine attacks are contraindicated after stroke.

  • Distinction between migraine aura and a transient ischemic attack can be challenging, particularly among the elderly.

Migraine is a chronic-intermittent primary headache disorder with episodes of headache that are unilateral or bilateral in location, often pulsating in quality, moderate to severe in intensity, and exacerbated by physical activity. Associated symptoms include nausea or vomiting, photophobia, and phonophobia. The prevalence of migraine is 12%–18% in females and 6%–8% in males. The prevalence of migraine with aura (which includes familial hemiplegic migraine [FHM]) is lower, around 4%, and about 25% of migraine patients have either migraine with aura or migraine both with and without aura. Aura is, in general, a recurrent disorder manifesting in attacks of reversible focal neurologic symptoms (mostly visual) that usually develops gradually over 5–20 minutes and lasts for less than 60 minutes. Various forms of migraine are recognized, generally classified according to the transient, though sometimes persistent, neurologic deficits that may precede, accompany, or outlast the headache phase. The most recent classification was published by the International Headache Society (IHS) in 2018 ( Table 43.1A ) .

TABLE 43.1A
Classification of Migraine Subtypes.
Modified from Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders ICHD-3., 3rd ed. Cephalalgia . 2018;38(1):1–211.
International Headache Society World Health Organization
1 ICHD-3 2 ICD-10NA 3 ICD-11 Diagnosis
1 G43 8A80 Migraine
1.1 G43.0 8A80.0 Migraine without aura
1.2 G43.1 8A80.1 Migraine with aura
1.2.1 G43.10 Migraine with typical aura
1.2.1.1 Typical aura with headache
1.2.1.2 G43.104 Typical aura without headache
1.2.2 G43.103 Migraine with brain stem aura
1.2.3 G43.105 8A80.10 Hemiplegic migraine
1.2.3.1 a Familial hemiplegic migraine
1.2.3.2 Sporadic hemiplegic migraine
1.2.4 G43.81 Retinal migraine
1.3 G43.3 8A80.2 Chronic migraine
1.4 G43.3 8A80.3 Complications of migraine
1.4.1 G43.2 8A80.30 Status migrainosus
1.4.2 G43.3 8A80.3Y Persistent aura without infarction
1.4.3 G43.3 Migrainous infarction
8B22.9 Migraine - induced stroke
1.4.4 G43.3 + b G40.x/G41.x Migraine aura triggered seizure
1.5 G43.83 NA Probable migraine
1.5.1 NA Probable migraine without aura
1.5.2 NA Probable migraine with aura
1.6 G43.82 8A80.3Y Episodic syndromes that may be associated with migraine
1.6.1 G43.82 Recurrent gastrointestinal disturbance
1.6.2 G43.821 Benign paroxysmal vertigo
1.6.3 G24.3 Benign paroxysmal torticollis
ICD10-G43.3 Codes for “complicated migraine,” and, ICD11: 8A80.Y codes for “Other specified migraine,” following both are coding for several different migraine subtypes.

a 1.2.3.1.1-1.2.3.1.3:FHM1-FHM3; 1.2.3.1.4 FHM with other gene locus.

b The additional code specifies the type of seizure,

Migraine with aura of different types, retinal or ocular migraine, FHM, and migraine with brain stem aura may mimic transient ischemic attack (TIA), or ischemic stroke may be associated with an increased stroke risk. Each may be transient, prolonged, or persistent. When the aura symptoms of a migraine attack persist for more than 24 hours, migrainous infarction is suspected.

Clinical Features

The most prevalent migraine syndromes include typical migraine headache without aura, and migraine headache associated with aura. Visual disturbances account for well over half the transient neurologic manifestations. Most frequently, these consist of positive phenomena such as stars, spark photopsia, complex geometric patterns, and fortification spectra. These positive phenomena may leave in their wake “negative” phenomena such as increasing scotoma and slowly developing hemianopia. The symptoms are characteristically slow in onset and slow in progression, although occasionally the onset is more abrupt, and a migraine headache may be confused with amaurosis fugax. Visual symptoms sometimes progress to visual distortion or misperception, such as micropsia or dysmetropsia. The patterns of symptoms indicate the spread of neurologic dysfunction from the occipital cortex into the contiguous regions of the temporal or parietal lobes. It is critical, in making the differential diagnosis from stroke, to establish that the neurologic deficit in aura crosses arterial territories. The second most common symptoms are somatosensory and characteristically hand and lower face (cheiro-oral) in distribution. Less frequently, the symptoms include aphasia, dysarthria, or clumsiness of one limb. Mostly, a slow, march-like progression of symptoms is characteristic.

Classification

The major problem that faces the clinician is a lack of consistency in the definition of migraine-related stroke in the studies conducted so far. Strict definition of terms is essential for future comprehensive epidemiologic or population-based studies. The following major questions arise:

  • Does stroke occur in the course of the migraine attack, causing true migraine-induced cerebral infarction?

  • Does migraine cause stroke because other risk factors for stroke are present to interact with the migraine-induced pathogenesis?

  • Can stroke present as a migraine syndrome, that is, symptomatic migraine?

Some of the latest developments serve to clarify the association between migraine and stroke. The IHS classification has led to improved definitions of migraine and migrainous cerebral infarction in a more specific comprehensive manner. New techniques of brain imaging have provided new insights into the relationship of the disorders through improvements in diagnosis.

Migrainous cerebral infarction (ICHD-3: 1.4.3) is described in the IHS classification as “one or more migraine aura symptoms associated with an ischemic brain lesion in the appropriate territory demonstrated by neuroimaging.”

Diagnostic criteria include:

  • A.

    A migraine attack fulfilling criteria B and C.

  • B.

    Occurring in a patient with 1.2 migraine with aura and typical of previous attacks except that one or more aura symptoms persist for greater than 60 minutes.

  • C.

    Neuroimaging demonstrates ischemic infarction in a relevant area.

  • D.

    Not better accounted for by another ICDH-3 diagnosis.

Table 43.1B presents an extended classification of stroke in association with migraine or migraine-related stroke. Included in this classification is migrainous cerebral infarction.

TABLE 43.1B
Overview of the Classification of Headache Attributed to Cranial or Cervical Vascular Disorder.
International Headache Society ICHD-3 Diagnosis
6.1 Headache attributed to cerebral ischemic event
6.2 Headache attributed to non-traumatic intracranial hemorrhage
6.3 Headache attributed to unruptured vascular malformation
6.4 Headache attributed to arteritis
6.5 Headache attributed to cervical carotid or vertebral artery disorder
6.6 Headache attributed to cranial venous disorder
6.7 Headache attributed to other acute intracranial arterial disorder
6.8 Headache attributed to genetic vasculopathy
6.9 Headache attributed to pituitary apoplexy
For details and subclassification see: https://ichd-3.org/6-headache-attributed-to-cranial-or-cervical-vascular-disorder/ .

Migrainous Cerebral Infarction

Definition: See previous discussion.

The major problem with the IHS classification is that it does not permit the diagnosis of migrainous infarction in patients who have migraine without aura. Perhaps migraine without aura, in some patients, begins in “silent” brain areas and has the same pathogenesis as migraine with aura. This possibility is indicated by the blood flow measurements reported by Woods and colleagues, who found a decrease of 30%–40% in cerebral blood flow (CBF) in the occipital lobe in a woman during an episode of migraine without aura. Migrainous cerebral infarction might occur in patients without other vascular risk factors.

Coexisting Stroke and Migraine

Definition: A clearly defined clinical stroke syndrome must occur remotely in time from a typical attack of migraine with aura.

Among young individuals, stroke is a rare event, whereas migraine is common. Clearly, the two conditions can coexist without migraine being a contributive factor to stroke. When the two conditions coexist in the young, the true pathogenesis of stroke may be difficult to elucidate. A comorbidity of stroke risk in migraine sufferers seems apparent from the case-control series reviewed later in this chapter, in which none of the strokes was directly induced by the migraine attack. This finding increases the clinical significance of coincident stroke and should serve to raise clinical consciousness of the need for stroke risk factor awareness in all migraine sufferers.

Stroke With Clinical Features of Migraine

Definition: A structural lesion unrelated to migraine pathogenesis that manifests as clinical features typical of migraine.

Symptomatic Cases

In symptomatic cases, established structural lesions of the central nervous system or cerebral vessels episodically cause symptoms typical of migraine with aura. Such cases should be termed “symptomatic migraine.” Migraine-like headache secondary to another disorder (symptomatic migraine) is coded as a secondary headache attributed to that disorder. Cerebral arteriovenous malformations frequently masquerade as migraine with aura. Migraine attacks associated with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) also may be symptomatic of the membrane dysfunction associated with this disorder. Subarachnoid hemorrhage, venous-sinus thrombosis, and viral meningitis can mimic migraine attacks with or without aura in patients who suffer from migraine or who have a family history of migraine.

Migraine Mimic

In this category, stroke due to acute and progressing structural disease is accompanied by headache and a constellation of progressive neurologic signs and symptoms indistinguishable from those of migraine. This might best be termed a migraine mimic but is also referred to as secondary migraine.

The diagnostic discrimination of a migraine mimic can be most difficult to define in patients with established migraine. Many of the cases described in the literature on the conceptual evolution of migraine-related stroke were likely migraine mimics, the diagnosis being hampered by limitation in investigative tools and uncertainty in the knowledge of migraine pathogenesis.

The issue of spontaneous carotid artery dissection is relevant because patients with migraine are at increased risk for dissections and because the occurrence of a dissection as a typical migraine mimic has been reported. Although the mechanism of pain generation is not clearly understood, the occurrence of headache is an expected finding, present in 60% of patients, and headache is more frequent in vertebral dissection, along with a variable incidence of ischemic complications, a combination that may mimic accompanied migraine. Fisher analyzed 21 selected cases of angiographically documented cervical carotid dissection, observing that almost all patients (19 of 21) had ipsilateral pain in one or more regions of the head, including forehead, orbit, temple, retro-orbit, side of head, and frontal region. In addition, 12 patients had neck pain, usually in the upper neck and localized to a region including the mastoid, the upper carotid, behind or below the angle of the jaw, and along the sternocleidomastoid muscle. The pain was usually severe, often sudden in onset, described equally as steady or throbbing, and occasionally accompanied by alterations in ipsilateral scalp sensation. The duration ranged from several hours to 2 years, with most lasting no longer than 3–4 weeks. About three-fourths of Fisher’s patients experienced ischemic complications, and in one-half, the headache preceded the ischemic event by a few hours to 4 days. Other common diagnostic findings were Horner syndrome, subjective bruit, dysgeusia, and visual scintillations.

Uncertain Classification

Complex or multiple factors : Many migraine-related strokes cannot be categorized with certainty.

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