Novel Imaging Phenotype in Spinal Cerebellar Ataxia Type 8: Symmetrical White Matter Changes without Cerebellar...

Spinal Cerebellar Ataxia Type 8 (SCA8) is a rare autosomal dominant neurodegenerative disorder characterized by progressive cerebellar dysfunction. It is caused by pathogenic expansions of a CTG/CAG trinucleotide repeat sequence within the ATXN8OS/ATXN8 gene locus on chromosome 13q21. Although cerebellar atrophy is widely recognized as a cardinal neuroimaging feature of SCA8, the phenotypic spectrum remains incompletely characterized. This study identified two cases of SCA8 through genetic analysis. Pedigree information was gathered and analyzed for all available family members. A systematic literature review was conducted to identify all published SCA8 cases with available neuroimaging data. The distinctive clinical and radiological features of SCA8 were analyzed through detailed case characterization integrated with a comprehensive review of existing literature. We report two genetically confirmed SCA8 cases exhibiting a previously undescribed neuroimaging phenotype. Case 1: A 36-year-old woman presented with a one-year history of progressive gait ataxia. Brain MRI revealed confluent, symmetric white matter signal abnormalities without cerebellar atrophy. Repeat expansion analysis detected a pathogenic CTG/CAG expansion of 9/77 in the ATXN8 gene. Case 2: A 64-year-old man (father of case 1) exhibited significant gait abnormalities, cognitive impairment and dysarthria. Brain MRI showed symmetric white matter lesions similar to case 1, with a CTG/CAG repeat length of 17/73. Notably, our systematic review revealed no prior reports of SCA8 presenting with isolated, symmetric white matter abnormalities in the absence of cerebellar atrophy. These findings delineate a novel neuroimaging phenotype of SCA8, characterized by symmetric white matter alterations without cerebellar volume loss. This atypical presentation expands the radiological spectrum of SCA8 and underscores the importance of considering repeat expansion disorders in the differential diagnosis of leukoencephalopathies, even in the absence of classic neurodegenerative imaging signatures.