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. Disclosure: Dr. Hermanson has nothing to disclose. Dr. Jhaveri has nothing to disclose. Dr. Stebbins has nothing to disclose. Dr. Dunn has nothing to disclose. Dr. Merkitch has nothing to disclose. Dr. Berry-Kravis has received personal compensation for activities with Seaside Therapeutics, Novartis, Roche, Neuren Pharmaceuticals, and Alcobra Pharma as a consultant. Dr. Hall has nothing to disclose.