Imaging biomarkers for early prediction of the transition from idiopathic late-onset cerebellar ataxia to multiple system atrophy

Abstract

Introduction: Idiopathic late-onset cerebellar ataxia (ILOCA) is a degenerative, non-hereditary form of adult-onset cerebellar ataxia. A subset of patients with ILOCA eventually develop multiple system atrophy of the cerebellar type (MSA-C), but imaging biomarkers that predict this transition remain unidentified. This study aimed to identify imaging biomarkers that may predict phenoconversion from ILOCA to MSA-C. Methods: A retrospective cohort of patients diagnosed with ILOCA who underwent baseline T1-weighted and diffusion-weighted magnetic resonance imaging (MRI) was analyzed. Patients were followed longitudinally and reclassified as ‘phenoconverters’ if they met diagnostic criteria for MSA-C, or as ‘non-phenoconverters’ otherwise. Clinical characteristics were compared between groups, and infratentorial volumetric and microstructural changes were assessed using diffusion tensor imaging (DTI). Results: Over a mean follow-up of 5.7 years, 13 of 45 patients (28.9 %) transitioned to a diagnosis of MSA-C. Phenoconverters exhibited more severe baseline ataxia compared to non-phenoconverters. While cerebellar volumes were similar between groups, phenoconverters had significantly reduced volumes in the pons and superior and middle cerebellar peduncles. Additionally, they demonstrated lower mean fractional anisotropy in the middle and inferior cerebellar peduncles. Conclusions: Patients with ILOCA who later develop MSA-C show early microstructural changes and volume loss in the pons and cerebellar peduncles. Combining infratentorial volumetry with DTI may offer complementary imaging biomarkers for predicting phenoconversion to MSA-C.