Parkinsonism is a Late, Not Rare, Feature of CADASIL: A Study on Italian Patients Carrying the R1006C Mutation

Background and Purpose— To describe parkinsonism as a clinical manifestation of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Methods— We report 5 patients carrying the R1006C mutation in the exon 19 of NOTCH3 gene. All cases presented late onset, slowly progressive parkinsonism, not responsive to l-dopa. We performed brain MRI and 123I-FP-CIT SPECT in all and in 3 additional patients carrying the same mutation but without parkinsonism. Four patients with parkinsonism underwent myocardial 123I-meta-iodobenzylguanidine scintigraphy. Results— In all patients, brain MRI showed widespread ischemic lesions in the periventricular white matter, the internal and external capsules, the basal ganglia, and thalami. 123I-FP-CIT SPECT showed symmetrical or asymmetrical reduction of tracer uptake in the putamen, with inconstant caudate involvement. Myocardial 123I-meta-iodobenzylguanidine scintigraphy resulted normal. Nigrostriatal denervation was also demonstrated in 2 patients without parkinsonism. Conclusions— In cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, parkinsonism may be a not rare, late onset manifestation. The clinical picture, the lack of response to dopaminergic treatment, and MRI findings suggest a vascular parkinsonism, which may be preceded by a protracted presymptomatic phase.