CADASIL: Migraine, Encephalopathy, Stroke and Their Inter-Relationships

Abstract

BackgroundMigraine is common in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) but its treatment responses are not well described, and its relationship to stroke risk unknown. Encephalopathy is a less common presentation; it has been suggested it is related to migraine. We characterised migraine patterns and treatment responses in CADASIL, and examined associations between migraine and both stroke risk and encephalopathy.Methods300 symptomatic CADASIL patients were prospectively recruited from a national referral clinic over a nineteen year period, from 1996 to 2015. Data was collected using a standardised questionnaire. Migraine was classified according to the International Classification of Headache Disorders, 3rd edition (beta version). A cross-sectional analysis was carried out on the data collected.ResultsMigraine was present in 226 (75.3%), and the presenting feature in 203 (67.7%). It was usually accompanied by aura (89.8%). Patients showed variable responses to a variety of drugs for migraine. Of 24 given triptans, 45.5% had consistent or partial responses. None had complications following triptans. Thirty-three (11.0%) patients experienced encephalopathy lasting on average 8.1 ± 3.4 days. Patients with migraine with aura had higher odds of encephalopathy (OR = 5.4; 95%CI 1.6–28.4; p = 0.002). Patients with confusional aura had higher odds of encephalopathy than those with other aura types (OR = 2.5, 95%CI = 1.0–5.8, p = 0.04). There was also no increase in risk of encephalopathy with sex or age at onset of migraine. Migraineurs had a lower stroke risk than non-migraineurs (HR = 0.46, 95%CI 0.3–0.6, p = 2.1x10-6).ConclusionsMigraine with aura is a prominent feature of CADASIL. Treatment responses are similar to those seen in the general migraine population and no complications were observed with triptans. Migraine with aura was associated with increased risk of encephalopathy suggesting they may share pathophysiological mechanisms. There was no increased stroke risk associated with migraine, but risk appeared to be reduced although this finding needs confirming.

Aura and Other Neurologic Dysfunction in or with Migraine

“…Arguing against CSD causing cerebral ischemia was the observation of a lower stroke risk in migraineurs when compared to non-migraineurs in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). 197 In a retrospective review of triptan and ergot use in 80 patients with either hemiplegic migraine or brainstem aura, no reported ischemic events were associated with the use of these vasoconstrictive agents. 198 Another possible explanation supported by the above evidence would be that cerebral ischemia can result in CSD in and/or near ischemic tissues resulting in aura and migrainous headache, rather than the CSD leading to aura and migraine which are in turn causative of cerebral ischemia.…”

“…In cases suggestive of migrainous infarction, vasospasm would be a consideration and potential alternative diagnosis. Arguing against CSD causing cerebral ischemia was the observation of a lower stroke risk in migraineurs when compared to non‐migraineurs in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) . In a retrospective review of triptan and ergot use in 80 patients with either hemiplegic migraine or brainstem aura, no reported ischemic events were associated with the use of these vasoconstrictive agents .…”

More than meets the eye in a ‘migraine’

“…However, with data on so few patients available, we do not know the prognosis of patients with this presentation, that is, the chance of recurrence and whether they share the same risk of stroke and dementia. Migraine is common in CADASIL, usually preceding other features, and >80% show some form of aura 2. Confusional aura (anterograde amnesia, disorientation, lasting <24 hours) occurs in 20% and may give an early clue to the diagnosis.…”

Single Gene Causes of Stroke

“…Migraine without aura is of no higher prevalence than in the general population. In contrast, a large 2016 series reported migraine with aura in 75% of symptomatic CADASIL patients, 15 a markedly high prevalence compared with the general population. Hemiplegic migraine occurs in 16% of patients, 15 and CADASIL encephalopathy, also called CADASIL coma, can be severe enough to require hospitalization in up to 11% of symptomatic CADASIL patients.…”

“…In contrast, a large 2016 series reported migraine with aura in 75% of symptomatic CADASIL patients, 15 a markedly high prevalence compared with the general population. Hemiplegic migraine occurs in 16% of patients, 15 and CADASIL encephalopathy, also called CADASIL coma, can be severe enough to require hospitalization in up to 11% of symptomatic CADASIL patients. 15 CADASIL encephalopathy is a particularly disabling severe form of migraine, characterized by prolonged (median of 8 days, range 3 to 17 days), but ultimately reversible reduced consciousness without another cause.…”