- 期刊
神經元核內包涵體病與腦部小血管疾病
NOTCH2NLC GGC Repeat Expansion in Patients with Cerebral Small Vessel Disease
並列摘要
Neuronal intranuclear inclusion disease (NIID), caused by GGC (guanine-guanine-cytosine) repeat expansion in the 5' untranslated region of NOTCH2NLC, is an autosomal-dominantly inherited neurodegenerative disease with diverse clinical presentations. NIID and cerebral small vessel disease (cSVD) share multiple overlapped features, including diffuse white matter hyperintensity on brain MRI, cognitive decline, gait disturbance, and acute neurological deficits appearing like stroke-like events. We found six of 197 (3%) unrelated patients with genetically unsolved vascular leukoencephalopathy harbored NOTCH2NLC GGC repeat expansion. Skin biopsy of one patient revealed eosinophilic, ubiquitin-positive, and p62-positive intranuclear inclusions in the cells of sweat gland and capillary, providing pathologic evidence for the involvement of small vessels in NIID. For the cSVD patients carrying GGC repeat expansion, gait disturbance and cognitive decline were common manifestations with a median onset age of 65 (59-69) years. They all had multiple neuroimaging features suggestive of cSVD, including diffuse white matter hyperintensities, lacunes, enlarged perivascular space, cerebral microbleeds, and old intracerebral hemorrhage. Four of the six patients also had linear hyperintensity in the corticomedullary junction on diffusion-weighted imaging, the characteristic neuroimaging feature of NIID. The present study suggests that NIID should be considered in patients manifesting cSVD, especially in those with characteristic neuroimaging feature of NIID.