Involvement of the Cerebellar Peduncles in Premutation Carriers: A Pictorial Review of Their Anatomy, Imaging, and Pathology.

The cerebellar peduncles (CPs) contain essential pathways connecting the cerebellum and other regions of the central nervous system, yet their role is often overlooked in daily medical practice. Individuals with the premutation are at risk of developing fragile X-associated tremor/ataxia syndrome (FXTAS), a late-onset neurodegenerative disorder. The major clinical and radiological signs of FXTAS are cerebellar gait ataxia, intention tremor, and T2-weighted MRI hyperintensity of the middle cerebellar peduncle (MCP sign). Over the years, metabolic and structural abnormalities have also been described in the CPs of premutation carriers, with some being associated with CGG repeat length and mRNA levels. Evidence seems to associate the clinical disfunction observed in FXTAS with MCP abnormalities. However, other tracts within the different CPs may also contribute to the symptoms observed in FXTAS. By integrating imaging and pathological data, this review looks to enhance the understanding of the functional anatomy of the CPs and their involvement in different pathological entities, with special interest in premutation carriers and FXTAS. This review, therefore, aims to provide accessible knowledge on the subject of the CPs and their functional anatomy through detailed diagrams, offering a clearer understanding of their role in premutation.