Deep Learning Cerebellar Magnetic Resonance Imaging Segmentation in Late-Onset GM2 Gangliosidosis: Implications for Phenotype.

Late-onset Tay-Sachs (LOTS) disease and late-onset Sandhoff disease (LOSD) have long been considered indistinguishable due to similar clinical presentations and shared biochemical deficits. However, recent magnetic resonance imaging (MRI) studies have shown distinct cerebellar atrophy associated with LOTS. In this study, we furthered this investigation to determine if the cerebellar atrophy is globally uniform or preferentially targets certain cerebellar regions. We utilized , a deep learning cerebellar specific segmentation and cortical thickness pipeline to analyze differences between LOTS (n=20), LOSD (n=5), and neurotypical controls (n=1038). LOTS had smaller volumes of the whole cerebellum as well as cerebellar lobules IV, V, VI, VIIB, VIIIA, VIIIB, IX, and both Crus I and II compared to both LOSD and neurotypical controls. LOTS patients also had smaller cortical thickness of cerebellar lobules V, VI, VIIB, VIIIA, VIIIB, and both Crus I and II compared to both LOSD and neurotypical controls. Cerebellar functional and lesion localization studies have implicated lobules V and VI in speech articulation and execution while lobules VI, Crus I, VIIA, among others, have been implicated in a variety of behaviors and neuropsychiatric symptoms. Our observations provide a possible anatomical substrate to the higher prevalence of dysarthria and psychosis in our LOTS but not LOSD patients. Future studies are needed for direct comparisons considering phenotypic aspects such as age of symptom onset, presence and severity of dysarthria and ataxia, full characterization of neuropsychiatric profiles, molecular pathology and biochemical differences to fully understand the dichotomy observed in these two diseases.