The Splenium of the Corpus Callosum Sign in Fragile X associated Tremor Ataxia Syndrome (FXTAS) (P2.125)

OBJECTIVE: To investigate the prevalence of white matter lesions in the corpus callosum splenium (CCS sign) in individuals with FXTAS. BACKGROUND: FXTAS is an adult-onset movement disorder that manifests as tremor, ataxia, and parkinsonism in premutation carriers of 55-200 CGG repeats in the 5’ promoter of FMR1. Recently, FXTAS was associated with CCS hyperintensities in a small case series at a frequency similar to the middle cerebellar peduncle (MCP) sign. DESIGN/METHODS: Demographics, FXTAS parameters (e.g. CGG repeats, symptoms), and MRI scans were collected from FXTAS subjects and age-matched controls, who had other movement disorders and negative FMR1 testing. A neuroradiologist who was blinded to carrier status assessed the scans for cerebral atrophy and hyperintensities in the MCP, brainstem, and CCS. RESULTS: Twenty-two FXTAS (61[percnt] men, mean CGG repeat size of 89) and 23 control (65[percnt] men, mean repeat size of 29) MRI scans were included. Both groups were predominantly white, non-Hispanic, and had a mean age at imaging of 67.5 (FXTAS, sd=6) and 64.7 (control, sd=12.4) years. Of the FXTAS subjects, 9 had definite, 10 had probable, and 3 had possible FXTAS. The majority of the controls had Parkinson’s disease (35[percnt]) or ataxia (25[percnt]). The following imaging findings were more frequent in the FXTAS subjects: CCS sign (p<0.01), MCP sign (p<0.01), cerebral atrophy (p=0.03), brainstem white matter disease (p=0.02). None of the clinical neuroradiology reports noted the CCS sign. CONCLUSIONS: FXTAS subjects had a higher prevalence of cerebral atrophy and hyperintensities in the CCS, MCP, and brainstem compared to age-matched controls. While cerebral atrophy and hyperintensities in the MCP and brainstem are current diagnostic criteria for FXTAS, the CCS sign is not widely recognized as a radiologic manifestation. However, this study demonstrates that the CCS sign may be an under-reported useful clinical marker to aid in the diagnosis of FXTAS.