Corpus Callosal Diffusivity Predicts Motor Impairment in Relapsing-remitting Multiple Sclerosis: a TBSS and Tractography Study

Motor deficits in relapsing remitting multiple sclerosis (RRMS) patients are monitored using standard measures of disability that assess performance ranging from walking ability to hand function, thus reflecting involvement of a variety of motor pathways. We investigated the relative contributions of diffuse white matter damage and focal lesions using diffusion tensor imaging (DTI), in predicting future worsening of hand function in RRMS. The nine hole peg test (NHPT), a test of fine hand motor control, was used to measure baseline upper limb function in 16 controls and 25 RRMS patients, and then performed at follow-up on 22 of these patients at 6 and 12 months. Tract-based spatial statistics (TBSS) were used across the whole brain as a non-hypothesis driven method for localizing white matter changes associated with motor deficits. Subsequently, we used probabilistic fiber tractography in the corticospinal tracts (CST) and the transcallosal hand motor (TCHM) fibers to assess the predictive power of diffusion metrics and/or functionally relevant visible lesion volumes on the decline of hand motor function over the next 12 months. While fractional anisotropy (FA) and radial diffusivity (RD) of both pathways were strongly associated with NHPT performance at baseline, only RD of the TCHM fibers was predictive of NHPT decline over the next 12 months. Neither total visible lesion load nor pathway specific lesion loads were indicative of NHPT performance or progression. The TCHM fibers may play an important role in modifying the effects of MS pathology on fine motor control, and RD in these fibers may be a sensitive biomarker for future disability.