Prevalence and characteristics of migraine in CADASIL

Abstract

Background and objective Migraine with aura (MA) is a major symptom of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We assessed the spectrum of migraine symptoms and their potential correlates in a large prospective cohort of CADASIL individuals. Methods A standardized questionnaire was used in 378 CADASIL patients for assessing headache symptoms, trigger factors, age at first attack, frequency of attacks and associated symptoms. MRI lesions and brain atrophy were quantified. Results A total of 54.5% of individuals had a history of migraine, mostly MA in 84% of them; 62.4% of individuals with MA were women and age at onset of MA was lower in women than in men. Atypical aura symptoms were experienced by 59.3% of individuals with MA, and for 19.7% of patients with MA the aura was never accompanied by headache. MA was the inaugural manifestation in 41% of symptomatic patients and an isolated symptom in 12.1% of individuals. Slightly higher MMSE and MDRS scores and lower Rankin score were detected in the MA group. Conclusion MA is observed in almost half of all CADASIL patients. Atypical aura symptoms are reported by more than one in two of them. MA is often inaugural, can remain isolated and is not associated with the severity of the disorder.

Clinical presentation of Y189C mutation of the NOTCH3 gene in the Polish family with CADASIL

“…The MA frequency usually decreases with the CADASIL progression (stroke event). The supposed explanation involves changes at the cortex level involving myelin content or neuronal/microglial activity, but it needs further studies [13]. The ischemic changes both in CT and MRI were observed in all sisters carrying the Y189C mutation in the NOTCH3 gene.…”

“…All of them together suggest that heterogeneity of the CADASIL phenotype may be associated with modifying effects of factors other than causative NOTCH3 mutations, e.g., hormonal status, Hcy level, APOE genotype as well as classic risk factors for stroke. Guey et al [13] suggest that the hormonal status may influence the onset of MA in CADASIL as it facilitates the CSD. It may explain the occurrence of a migraine during pregnancy (II-2)/after childbirth (II-11) or its intensification after childbirth (II-6) in our patients with the Y189C mutation of NOTCH3.…”

Pathophysiological Mechanisms and Potential Therapeutic Targets in Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (CADASIL)

“…Migraine with aura occurs in 20-40% of affected subjects and is usually the presenting symptom of the disease. Notably, one-half of patients complain of at least one atypical aura, and attacks frequency varies among individuals (Chabriat et al, 2009;Guey et al, 2016). Cerebral transient ischemic attacks and infarctions are the most frequent manifestations of the disease, occurring in 60-85% of symptomatic individuals (Chabriat et al, 2009;Drazyk et al, 2019).…”

Headache in cerebrovascular diseases

“…MA in CADASIL is the most commonly typical aura with visual or sensory symptoms. Frequency of migraine can vary, but a majority of patients have less than one attack per month, as high as 80% in one 2015 study 28. Women with CADASIL are more likely to have migraine aura than men.…”