Migraine With Aura and Brain Magnetic Resonance Imaging Abnormalities in Patients With CADASIL

Abstract

Background: Migraine with aura (MA) is one of the clinical hallmarks of CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), a small vessel disease of the brain caused by mutations in the NOTCH3 gene, but its exact mechanisms are unknown. Objectives: To describe the patterns of MA in CADASIL and to compare brain magnetic resonance signal abnormalities between CADASIL patients with and without MA. Design: Comparison of brain magnetic resonance signal abnormalities between cases and controls. Setting: Patients with CADASIL seen at Lariboisière Hospital. Patients: Forty-one CADASIL patients with MA and 31 age-matched CADASIL controls without MA. Results: The mean age at onset of MA was significantly younger in women compared with men and occurred a mean of 15 years prior to stroke onset. A majority of patients (56%) reported at least 1 migraine attack with atypical aura. All CADASIL patients either with or without MA had white matter signal abnormalities on T2-weighted imaging. There was no difference in the frequency and distribution of brain signal abnormalities between CADASIL patients with and without MA. Conclusions: In CADASIL, MA is characterized by an unusually high frequency of attacks of migraine with atypical aura. The distribution and extent of magnetic resonance signal abnormalities did not differ according to migraine phenotype.

CADASIL: pathogenesis, clinical and radiological findings and treatment

“…The first migraine attacks occur before 20 years of age 44,54 and may precede or be linked to early neuroradiological changes -punctate hyperintensities in deep hemisphere or periventricular white matter -that may also be present in some individuals with primary migraine 30 . Women with CADASIL and migraine with aura tend to have symptom onset earlier than affected men 43 . In the study by Dichgans et al 50 , migraine was present in 30% of men and 44% of women, and 95% of patients affected by migraine headaches presented uo to 38 years of age; also, 14% reported increased frequency or severity of migraine near the first ischemic event.…”

“…Neuroradiological abnormalities, which may be present from childhood 41 , are often already detected at symptom onset and are almost universally present in symptomatic patients (possible exception in individuals with migraine only) or around 35 years 42,43 . CADASIL may be classified in three clinical/radiological stages 44 : I: generally between 20 to 40 years of age, with migraine and MRI showing white matter-defined lesions 42 .…”

“…As in primary migraine with aura, visual or sensory symptoms predominate. However, more than 50% of individuals may exhibit atypical, hemiplegic or prolonged auras 43 , and even rarer presentations, with meningism, mental confusion, fever and coma 55 . The frequency of attacks varies between affected individuals, from less than one to several attacks a month 56 .…”

Comorbid neuropathologies in migraine

“…Brain magnetic resonance imaging (Fig. 3) is always abnormal in CADASIL patients, showing ischaemic areas and white matter changes on T2-weighted images; the diagnosis may be further confirmed by a skin biopsy with immunostaining of Notch 3 antibodies [25][26][27].…”

Migraine in the era of precision medicine

“…Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a monogenic-inherited form systemic vasculopathy linked to mutations in the Notch3 gene (located on chromosome 19p13.2-p13.1), which encodes a cell surface receptor (53). The incidence of migraine with aura in CADASIL is five times greater compared with the general population (54,55).…”