Very high prevalence of right-to-left shunt on transcranial Doppler in an Italian family with cerebral autosomal dominant angiopathy with subcorticalinfarcts and leukoencephalopathy

Background and Purpose: Cerebral autosomal dominant angiopathy with subcort ical infarcts and leukoencephalopathy (CADASIL) is an autosomal dominant he reditary disease whose clinical expression is a stepwise subcortical vascul ar dementia. Initial presentation of the disease involves transient or stab ilized focal neurological deficits, migraine and mood changes. Recently, a high prevalence of right-to-left shunt (RLS) due to patent foramen ovale ha s been reported in subjects with migraine. The aim of our study was to dete rmine the prevalence of RLS in CADASIL with and without migraine. Methods: We performed transcranial Doppler with gaseous contrast in 5 members of an Italian family with CADASIL, diagnosed by means of genetic and skin biopsy criteria. We then compared the prevalence of RLS in 40 consecutive subjects with juvenile stroke, 80 asymptomatic subjects affected by migraine with a ura and 50 normal controls. Results: A very high prevalence of RLS was foun d in CADASIL patients (4/5, 80%), as opposed to young subjects with ischemi c stroke (15/40, 37%), asymptomatic subjects with migraine (32/80, 40%) and normal controls (8/50, 16%). All the subjects with CADASIL and migraine (4 /4) showed RLS. The difference between CADASIL patients and controls was hi ghly significant (p = 0.006). Conclusions: We suggest an association betwee n CADASIL and RLS, possibly due to the abnormal development of the endocard ial cushion influenced by Notch 3 mutation. Our hypothesis needs to be test ed in larger samples. Copyright (C) 2001 S. Karger AG, Basel.