Radiologically isolated syndrome (RIS) is often a pre-clinical form of multiple sclerosis (MS) detected incidentally when MRIs are obtained for reasons other than suspicion for MS. Volume loss in the cerebellum has been associated with motor and cognitive impairment in MS patients, most pronounced in patients with progressive disease. Whether cerebellar volume loss might be present in RIS prior to clinical symptoms of MS has not been investigated.

To compare volumes of posterior fossa structures in RIS subjects compared with healthy controls.

21 healthy individuals fulfilling 2009 criteria for RIS were retrospectively identified at the UCSF MS Center along with 38 age- and sex-matched healthy controls (HC). Subjects were scanned on a single 3T GE Signa scanner using a standardized protocol. White matter (WM) lesions were segmented on 3D T1-weighted images using a semiautomatic segmentation technique. Lesion-filled 3D T1-weighted images were segmented into gray matter (GM), WM and CSF using Statistical Parametric Mapping (SPM12) software. Cerebellar GM, WM and brainstem volumes were calculated on the lesion-filled 3D T1-weighted images using a customized version of Spatially Unbiased Infratentorial Toolbox version 3.2 in SPM12.

A general linear model adjusted for age and sex was used to assess the difference in normalized infratentorial structural volumes between RIS and HC. All statistical analyses were completed using SPSS (v. 19.0, Chicago, III). RIS subjects showed significant decreases in cerebellar WM (p = 0.003) and anterior cerebellar GM volumes (p = 0.005) compared to HC. Significant differences in posterior cerebellar GM (p = 0.134), total cerebellar GM and brainstem volumes (p = 0.172) between RIS and HC were not observed.

Cerebellar atrophy is present in RIS subjects. RIS has already been associated with atrophy in other areas of the brain, notably the thalamus. Further longitudinal studies may clarify the significance of these atrophy patterns.