Dataset Information

Extensive Leukoencephalopathy in Spastic Paraplegia Type 4: Possible Role of Cerebral Autosomal Arteriopathy With Subcortical Infarcts and Leukoencephelopathy.

ABSTRACT: Despite recent advances in next-generation sequencing, the underlying etiology of adult-onset leukoencephalopathy has been difficult to elucidate. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a representative hereditary adult-onset leukoencephalopathy associated with vasculopathy. Leukoencephalopathy in spastic paraplegia type 4 (SPG4) is known to be rare, but it might be underestimated because most spastic paraplegia with leukoencephalopathy is rarely considered. We report a case of co-occurring SPG4 and CADASIL. A 61-year-old male presented with sudden visual impairment after a headache. He showed a spastic gait and had a family history with similar symptoms. An SPG4 gene mutation and a pathogenic variant in the NOTCH3 gene were found. This case shows that the diverse and complex clinical manifestations of patients with extensive leukoencephalopathy are related to more than one gene mutation. We also suggest the necessity for relevant genetic tests in the diagnosis of adult-onset leukoencephalopathy.

SUBMITTER: Jung JH

PROVIDER: S-EPMC8820873 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Extensive Leukoencephalopathy in Spastic Paraplegia Type 4: Possible Role of Cerebral Autosomal Arteriopathy With Subcortical Infarcts and Leukoencephelopathy.

Jung Jin Ho JH Seo Jung Hwa JH Lee Sukyoon S Heo Young Jin YJ Kim Donghyun D Chung Eun Joo EJ Oh Seong-Il SI

Journal of movement disorders 20211224 1

Despite recent advances in next-generation sequencing, the underlying etiology of adult-onset leukoencephalopathy has been difficult to elucidate. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a representative hereditary adult-onset leukoencephalopathy associated with vasculopathy. Leukoencephalopathy in spastic paraplegia type 4 (SPG4) is known to be rare, but it might be underestimated because most spastic paraplegia with leukoencephalo ...[more]

PMID: 34937161

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Project description:Arteries in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) are susceptible to smooth muscle loss and fibrosis, but the molecular components underlying these dramatic vascular changes are not well characterized. The purpose of this study was to investigate the distribution of collagen isoforms in the cerebral vessels of North American CADASIL patients with classical NOTCH3 mutations. Expression of types I-VI collagen in brains obtained at autopsy from six CADASIL patients with cysteine-altering mutations in NOTCH3 was compared to control brain expression. We identified a consistent increase of types I, III, IV, and VI collagen in CADASIL brains. Strong accumulation of types I, III, IV and VI collagen was noted in all calibers of vessels, including small and medium-sized leptomeningeal arteries, small penetrating white matter arteries, and capillaries. Within leptomeningeal arteries, where we could define the three tunicae of each vessel, we found distinct collagen subtype distribution patterns in CADASIL. Types I and III collagen were largely found in either adventitial/medial or transmural locations. Type IV collagen was strictly intimal/medial. Type VI collagen was adventitial or adventitial/medial. Within the thickened penetrating arteries of CADASIL patients, all four collagens extended through most of the arterial wall. We observed increased staining of capillaries in CADASIL for types I, IV, and VI collagen. In conclusion, brain vascular collagen subtypes are increased in CADASIL in multiple layers of all sizes of arteries, with disease-specific changes most prominent in the tunica media and thickened small penetrating vessels. In diseased arteries, types I, III, and VI collagen spreads from an external location (adventitia) into the vascular media, while type IV collagen accumulates in an internal pattern (intima and media). These observations are consistent with a pathological role for collagen accumulation in the vascular media in CADASIL.

Dataset Information

Extensive Leukoencephalopathy in Spastic Paraplegia Type 4: Possible Role of Cerebral Autosomal Arteriopathy With Subcortical Infarcts and Leukoencephelopathy.

Publications

Extensive Leukoencephalopathy in Spastic Paraplegia Type 4: Possible Role of Cerebral Autosomal Arteriopathy With Subcortical Infarcts and Leukoencephelopathy.

Similar Datasets

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