ISCHEMIC STROKE / CLASSIFICATION AND ETIOPATOGENESIS

Stroke and migraine

Created 17/02/2023, last revision 18/02/2023

migraine is the most common neurological disorder, affecting 10-15% of the adult population
there is increasing evidence of an association between migraine and vascular disease (ischemic stroke, subclinical brain lesions, cardiac events, and vascular mortality) [Lee, 2016] [Anderson,2013] [Stang,2005]
- a 2-fold increased risk of ischemic stroke (RR ∼ 2.16) in patients with migraine with aura has been demonstrated in several population-based studies. However, these infarcts are not migrainous infarcts, and the mechanisms underlying the increased risk of ischemic stroke in migraineurs remain unclear
- the risk increases with the frequency of migraine attacks
- most studies have shown no association between migraine without aura and ischemic stroke
the risk of stroke is increased in young women (< 45 years) with migraine with aura (or with a history of status migrainosus), along with smoking and oral contraceptive use [Millhaud,2001]
- in men, the association between migraine and stroke is still controversial
however, the absolute risk of stroke is low and migrainous stroke is very rare despite the high prevalence of migraine

Etiopatogenesis

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population-based evidence suggests that some patients with migraine (with and without aura) have an increased risk of subclinical lesions in certain brain areas [Kruit, 2004]

criteria for migraine with aura are met
one of the aura symptoms lasts > 1 week and imaging studies exclude stroke in the corresponding territory

Stroke-like Migraine Attacks after Radiation Therapy (SMART) [Black, 2006]
late sequelae of radiotherapy (separated by several years)
headache (sometimes with aura) with prolonged but reversible neurological deficits (lasting up to several weeks)
MRI shows diffuse meningeal enhancement, that resolves spontaneously

headache + focal neurological deficits + CSF pleocytosis [Cifelli, 2011]
- pleocytosis (> 100)
- protein elevation
- no evidence of OCB or other CSF abnormality
fever is sometimes present
usually affects young males
appropriate investigations must exclude neuroinfection
MRI and angiography are normal
the condition usually lasts 6-12 weeks and resolves spontaneously

antiplatelet therapy
- choose aspirin or clopidogrel
- cilostazol and dipyridamole may provoke migraine-like attacks in migraineurs
statins may have a prophylactic effect on migraine → see here
- statins reduce the expression of CGRP and substance P and attenuate NF-κB activation in the caudal trigeminal nucleus
most antihypertensive drugs have some prophylactic effect on migraine [Lee, 2016]
- beta-adrenergic blockers, calcium channel blockers, some angiotensin receptor blockers, and angiotensin-converting-enzyme inhibitors
there is a theoretical risk of triptans and CGRP antagonists in patients with previous stroke (via vasoconstriction) [Aradi, 2019]
- however, according to AHA/ASA 2021, no clear recommendation can be made due to a lack of data
  - population-based studies show no evidence that triptans lead to an increased risk of vascular events
- it is unclear whether the increased risk of stroke is related to therapy or migraine severity
- stroke rarely occurs in migraineurs who do not abuse ergots or triptans
prophylactic migraine therapy does not reduce the risk of stroke [Øie, 2019]

antithrombotics and statins are not necessary for primary stroke prevention (unless indicated for other reasons)
risk factor modification is suggested (smoking cessation, abstinence from oral contraceptives, proper blood pressure control)
some drugs used for migraine prophylaxis may also be beneficial in reducing vascular risk