Nandakumar Nagaraja, MD

Ragno M, Berbellini A, Cacchiò G, AMancaA, Di Marzio F, Pianese L, et al. Parkinsonism is a Late, Not Rare, Feature of CADASIL: A Study on Italian Patients Carrying theR1006C Mutation. Stroke. 2013.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small-vessel disease caused by mutations in the NOTCH3 gene. Ragno and colleagues report 5 CADASIL patients with R1006C mutation in the exon 19 of the NOTCH3 gene who develop parkinsonism during the late stage of the disease. 

These patients are characterized by slow onset of parkinsonism symptoms after the diagnosis of CADASIL with early shuffling of gait, akathesia, rigidity, and postural instability but with rare presence of tremor. Symptoms are bilateral and non responsive to treatment with levodopa unlike idiopathic Parkinson’s Disease. MRI shows increased signal in periventricular white matter, internal and external capsules, basal ganglia and thalamus.

Parkinsonism was seen in only 5 (11%) of the total 45 CADASIL patients with R1006C mutation followed by the authors. Based on previous literature basal ganglia symptoms were present in 48% of patients older than 60 years. Parkinsonism is probably a late feature of many CADASIL patients irrespective of type of mutation in the NOTCH3 gene because of the involvement of basal ganglia and its connections. The significance of different types of NOTCH3 mutation in these patients causing phenotypic variability in the presentation of parkinsonism symptoms remains to be determined.