Headache associated with ischemic cerebrovascular disease

Hans-Christoph Diener MD PhD (

Dr. Diener of the University of Duisburg-Essen received honorariums from Allergan, Lilly, Novartis and Teva for service as an advisor or speaker; financial support from Electrocore for research projects; and honorariums from WebMD for speaking engagements.

Shuu-Jiun Wang MD, editor. (

Dr. Wang of the Brain Research Center, National Yang-Ming University, and the Neurological Institute, Taipei Veterans General Hospital, received consulting fees from Eli Lilly, Daichi-Sankyo, and Novartis for advisory board membership and honorariums from Bayer as a moderator.

Originally released July 17, 1995; last updated December 2, 2020; expires December 2, 2023


Headache often accompanies acute ischemic stroke. Observational studies indicate that 6% to 44% of patients with acute ischemic stroke report headache in close temporal relation to the event. The onset headache is more often seen in posterior circulation strokes than in strokes in other vascular territories. The pathophysiology of headache associated with acute ischemic stroke includes edema, hemorrhagic transformation, and changes in the trigeminovascular system.

Key points


• Headache is the leading symptom in subarachnoidal hemorrhage


• Headache is more frequent in ischemic stroke in the posterior circulation than in the anterior circulation


• Acute severe headache with neurologic signs requires cerebral imaging, or lumbar puncture, or both

Historical note and terminology

The first description of a relationship between headache and cerebral vessel occlusive disease dates back to 1664, when Thomas Willis described the neurovascular autopsy findings of a patient with asymptomatic right carotid occlusion. This patient, who died from unrelated causes and never suffered a stroke, had reported head pain on the side opposite the occlusion. At autopsy, Willis found the left carotid and the vertebral arteries dilated up to 3 times the normal size. He hypothesized that this compensatory dilation and increase of blood flow might have been the cause of the patient's head pain:


For indeed, nature had substituted a sufficient remedy against that danger of an apoplexy; to wit, the vertebral artery on the same side, in which the carotidick was wanting, the bulk of the pipe being enlarged, became thrice as big as both its pipes on the other side: because, the blood being excluded the carotidick, adding itself to the wonted provision of the vertebral artery, and flowing with a double flood into the same belly, had so dilated the channel of that artery above measure. This gentleman, about the beginning of his sickness, was tormented with a cruel pain of the head towards the left side. The cause whereof cannot be more probably assigned, than that the blood excluded from the right carotidick artery, when at first it rushed more impetuously in the left, had distended the membrane... (Willis 1664).

Fisher reported the first extensive study of clinical, arteriographic, and pathologic information as well as detailed descriptions of the headache characteristics in occlusive disease of various cerebral vessels (Fisher 1968). A number of authors subsequently provided detailed, but often conflicting, information on the frequency, features, and pathogenesis of headache in ischemic cerebrovascular disease (Welch and Bousser 2000).

Classifications include the following:

Headache associated with ischemic stroke. The International Headache Society classifies headache associated with ischemic cerebrovascular disease as headache associated with ischemic stroke, usually with acute onset and associated with focal neurologic signs (Headache Classification Committee of the International Headache Society 2018). Diagnostic criteria are as follows:

A. Any new headache fulfilling criteria C and D

B. Acute ischemic stroke has been diagnosed

C. Evidence of causation demonstrated by either or both of the following:


1. headache has developed in very close temporal relation to other symptoms and/or clinical signs of ischemic stroke, or has led to the diagnosis of ischemic stroke


2. headache has significantly improved in parallel with stabilization or improvement of other symptoms or clinical or radiological signs of ischemic stroke

D. Either of the following:


1. headache has resolved within 3 months


2. headache has not resolved but 3 months have not yet passed

E. Not better accounted for by another ICHD-3 diagnosis

When a new headache occurs for the first time in close temporal relation to a vascular disorder, it is coded as a secondary headache attributed to the vascular disorder. This is also true if the headache has the characteristics of migraine, tension-type, or cluster headache. When a preexisting primary headache is made worse in close temporal relation to a vascular disorder, there are 2 possibilities, and judgment is required. The patient can either be given only the diagnosis of the preexisting primary headache, or can be given both this diagnosis and the diagnosis of headache attributed to the vascular disorder. Factors that support adding the latter diagnosis are as follows: (1) a close temporal relation to the vascular disorder, (2) a marked worsening of the preexisting headache, (3) good evidence that the vascular disorder can aggravate the primary headache, and (4) improvement of the headache after the acute phase of the vascular disorder.

Headache attributed to ischemic stroke (cerebral infarction, IHS 6.1.1) is described as a new headache developing simultaneously with or in close temporal relationship to signs or other evidence of ischemic stroke associated with neuroimaging confirmation of ischemic infarction.

A new entity in The International Classification of Headache Disorders, 3rd edition, is persistent headache attributed to past ischemic stroke (cerebral infarction) (IHS, which is described as headache caused by ischemic stroke and persisting for more than 3 months after the stroke has stabilized. Diagnostic criteria are as follows:


Headache previously diagnosed as acute headache attributed to ischemic stroke (cerebral infarction), and fulfilling criterion C


The ischemic stroke has stabilized, spontaneously or through treatment


Headache has persisted for >3 months after stabilization of the ischemic stroke


Not better accounted for by another ICHD-3 diagnosis

This entity affects up to 23% of all patients after stroke (Lai et al 2018). The persistent headaches have tension-type features (Widar et al 2002). Risk factors include younger age, female sex, preexisting headache disorders, and comorbid depression. A systematic review collected data on stroke mimics in patients with migraine with aura between 1995 and 2017 (Terrin et al 2018). Migraine with aura was responsible for 1.79% of all the emergency stroke unit evaluations and represented 12.24% of stroke mimics in the group not treated with systemic thrombolysis; 6.6% of systemic thrombolysis administrations are performed in patients without an acute ischemic stroke, and migraine with aura is responsible for 18% of these. The reported rate of adverse events was very low (0.01%).

In many cases, the patient has previously fulfilled criteria for migraine with neurologic aura, and the present attack is typical of previous attacks. However, neurologic deficits are not completely reversible within 7 days, and other causes of infarction are ruled out by appropriate investigations.

Migraine-induced stroke. The diagnostic criteria are as follows: (1) the present attack in a patient with 1.2 migraine with aura is typical of previous attacks except that 1 or more aura symptoms persist for longer than 60 minutes; (2) neuroimaging demonstrates ischemic infarction in a relevant area; and (3) symptoms are not attributed to another disorder.

Ischemic stroke in a migraine sufferer may be categorized as a cerebral infarction of another cause coexisting with migraine, a cerebral infarction of another cause presenting with symptoms resembling migraine with aura, or a cerebral infarction occurring during the course of a typical migraine with aura attack. Only the last fulfills criteria for 1.5.4 migrainous infarction.

Coexisting stroke and migraine. A clearly defined clinical stroke syndrome must occur remotely in time from a typical attack of migraine. Stroke in the young is rare, and migraine is common. Clearly, the 2 conditions can coexist without migraine being a contributive factor to stroke. When the 2 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-controlled series (reviewed later in this article), wherein none of the strokes were induced by the migraine attack. This increases the clinical significance of coincident stroke and should serve to raise clinical consciousness to the need for stroke risk factor awareness in all migraine sufferers (Bousser and Welch 2005). A Scandinavian study found a prevalence of migraine of 20.6% in 175 stroke patients. Stroke patients with migraine were younger, had more frequently a patent foramen ovale, and less frequently had atrial fibrillation (Lantz et al 2015). A study from Belgium found a migraine prevalence of 11.2% in 323 stroke patients (Taheri et al 2015).

Stroke with clinical features of migraine. A structural lesion unrelated to migraine pathogenesis presents with clinical features typical of migraine. In symptomatic cases, established structural lesions of the central nervous system or cerebral vessels episodically cause symptoms typical of migraine with neurologic aura. Such cases should be termed symptomatic migraine (Olesen et al 1993). Cerebral arteriovenous malformations frequently masquerade as migraine with aura (Silvestrini et al 1992). 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 (Chabriat et al 1995; Davous 1998). 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 mimicking stroke. Migraine with aura may mimic an acute ischemic stroke (Purdy and Diener 2018). In this situation, some patients are treated with thrombolysis, and the proper diagnosis of migraine aura is made at a later point in time.

SMART syndrome. Stroke-like migraine attacks after radiation therapy involve complex migraine attacks with focal neurologic symptoms in patients who undergo cranial irradiation for the treatment of CNS malignancies (Kerklaan et al 2011). Neurologic symptoms can last for days and may include visual loss, weakness, aphasia, confusion, sensory loss, or seizures (Armstrong et al 2014).

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