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

Abstract

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.

Quantitative brain morphometry identifies cerebellar, cortical, and subcortical gray and white matter atrophy in late‐onset Tay‐Sachs disease

“…The morphometric analysis confirmed the finding of pontocerebellar atrophy in accordance with our earlier published results based on manual semiquantitative measurements 11 . With almost 60% of new patients, the present dataset can be considered to mostly not overlap with the previous study, so the finding of pontocerebellar atrophy was confirmed in a largely independent cohort.…”

“…Accordingly, many LOTS patients retrospectively report being clumsy during childhood, long before they seek neurologic care 41 . The relatively weak association between the severity of ataxia and cerebellar atrophy reported previously 11,41 and also shown in our current study suggests that the occurrence of prominent ataxia in the disease course may be linked not only to progression of cerebellar degeneration but also to the loss of compensatory mechanisms or lesion of ascending spinocerebellar pathways.…”

“…The median age at the MRI exam used for the analysis in this study was 42.5 years (range 20–70 years). Six patients included in this study were also assessed in a previous imaging study focused on semiquantitative parameters of cerebellar and brainstem atrophy 11 …”

“…The lobar atrophy and corpus callosum thinning have been reported, but the findings to date have been inconsistent in the descriptions resulting from visual assessments of brain MRI 11 . In a recent brain MRI and spectroscopic study, 10 late‐onset GM2‐gangliosidosis (including 7 LOTS) patients were compared to seven controls; volumetric and cortical thickness analysis showed reduced cerebellar volumes with decreased N ‐acetylaspartate, increased myo‐inositol and greater thickness of the left fusiform gyrus in the patient group 12 .…”

Clinical and imaging predictors of late‐onset GM2 gangliosidosis: A scoping review

“…This low prevalence, may be related to visually assessing scans, as opposed to detailed, quantitative measurements, particularly as Májovská et al. suggested that pontocerebellar atrophy may represent a cornerstone of imaging diagnosis in LOTS 32 . The presence of brainstem neuropathological abnormalities has been variable across limited pathological studies 4,6,7 .…”