Pontocerebellar atrophy is the hallmark neuroradiological finding in late-onset Tay-Sachs disease

Purpose Late-onset Tay-Sachs disease (LOTS) is a form of GM2 gangliosidosis, an autosomal recessive neurodegenerative disorder characterized by slowly progressive cerebellar ataxia, lower motor neuron disease, and psychiatric impairment due to mutations in the HEXA gene. The aim of our work was to identify the characteristic brain MRI findings in this presumably underdiagnosed disease. Methods Clinical data and MRI findings from 16 patients (10F/6 M) with LOTS from two centers were independently assessed by two readers and compared to 16 age- and sex-related controls. Results Lower motor neuron disease (94%), psychiatric symptoms—psychosis (31%), cognitive impairment (38%) and depression (25%)—and symptoms of cerebellar impairment including dysarthria (94%), ataxia (81%) and tremor (69%), were the most common clinical features. On MRI, pontocerebellar atrophy was a constant finding. Compared to controls, LOTS patients had smaller mean middle cerebellar peduncle diameter ( p < 0.0001), mean superior cerebellar peduncle diameter ( p = 0.0002), mesencephalon sagittal area ( p = 0.0002), pons sagittal area ( p < 0.0001), and larger 4 th ventricle transversal diameter ( p < 0.0001). Mild corpus callosum thinning (37.5%), mild cortical atrophy (18.8%), and white matter T2 hyperintensities (12.5%) were also present. Conclusion Given the characteristic clinical course and MRI findings of the pontocerebellar atrophy, late-onset Tay-Sachs disease should be considered in the differential diagnosis of adult-onset cerebellar ataxias.