Case Report: Progressive Asymmetric Parkinsonism Secondary to CADASIL Without Dementia

Abstract

Parkinsonism is a rare phenotype of cerebral autosomal dominant arteriopathy with subcortical infarction and leukoencephalopathy (CADASIL), all of which involve cognitive decline. Normal cognition has not been reported in previous disease studies. Here we report the case of a 60-year-old female patient with a 2-year history of progressive asymmetric parkinsonism. On examination, she showed severe parkinsonism featuring bradykinesia and axial and limb rigidity with preserved cognition. Magnetic resonance imaging (MRI) revealed white matter hyperintensity in the external capsule and periventricular region. Dopaminergic response was limited. A missense mutation c.1630C>T (p.R544C) on the NOTCH3 gene was identified on whole-exome sequencing, which confirmed the diagnosis of vascular parkinsonism secondary to CADASIL. A diagnosis of CADASIL should be considered in asymmetric parkinsonism without dementia. Characteristic MRI findings support the diagnosis.

Keywords: case report; cerebral autosomal dominant arteriopathy with subcortical infarction and leukoencephalopathy; cognition; parkinsonism; rapid eye movement sleep behavior disorder (RBD).

Figure 1

MRI, FDG-PET, VMAT2-PET, skin biopsy, and Sanger sequencing. (A1) FLAIR image shows white matter hyperintensity of the external capsule (yellow arrow). (A2) FLAIR image shows periventricular white matter hyperintensity (yellow arrow). (A3) Bilateral temporal poles show normal signal. (B) Flair image revealed no clearly cerebellar atrophy. (C) FDG-PET reveals hypometabolism in the right putamen. (D) VMAT2 indicates low-intensity signals in right putamen. (E) Skin biopsy shows granular osmiophilic material near the basement membrane of arteriolar smooth muscle cells (red arrow). (F) Sanger sequencing confirmed the mutation c. 1630C>T (p.R544C). MRI, magnetic resonance imaging; FDG-PET, fluorodeoxyglucose-positron emission tomography; FLAIR, fluid-attenuated inversion recovery; VMAT2, vesicular monoamine transporter type 2.