ABSTRACT
BACKGROUND: The gene SYNE1 is highly expressed in the cerebellum and its dysfunction is related to an autosomal recessive ataxia (SYNE1-ataxia). The disease was firstly considered a pure cerebellar ataxia however, recent studies have described a broader clinical presentation, including motor neuron disease symptoms. OBJECTIVES: To investigate cerebellar and potential extra-cerebellar changes in SYNE1-ataxia using multimodal neuroimaging analyses. METHODS: Six patients completed clinical and imaging exams, and were compared to age-gender-matched healthy controls. Gray matter was analyzed using FreeSurfer and CERES for brain and cerebellum, respectively. White matter was analyzed with DTI-TBSS while we used SpineSeg for spinal cord analysis. RESULTS: We found significantly reduced cortical thickness (pâ¯<â¯0.05, FDR-corrected) in primary and association cortices, and volume reduction in subcortical structures, brainstem and cerebellum. White matter was found disrupted in both brain and cerebellum (pâ¯<â¯0.05, FWE-corrected). These results are consistent with the expression of the SYNE1 mRNA and its encoded protein in the brain. We failed to demonstrate spinal cord changes. CONCLUSIONS: SYNE1-ataxia is, therefore, a relatively common cause of recessive ataxia characterized by complex multisystemic neurostructural changes consistent with the phenotypic heterogeneity and neuroimaging configures a potential marker of the disease.
