Early red nucleus atrophy in relapse-onset multiple sclerosis

No study has investigated red nucleus (RN) atrophy in multiple sclerosis (MS) despite cerebellum and its connections are elective sites of MS-related pathology. In this study, we explore RN atrophy in early MS phases and its association with cerebellar damage (focal lesions and atrophy) and physical disability. Thirty-seven relapse-onset MS (RMS) patients having mean age of 35.6 +/- 8.5 (18-56) years and mean disease duration of 1.1 +/- 1.5 (0-5) years, and 36 age- and sex-matched healthy controls (HC) were studied. Cerebellar and RN lesions and volumes were analyzed on 3 T-MRI images. RMS did not differ from HC in cerebellar lobe volumes but significantly differed in both right (107.84 +/- 13.95 mm(3)vs. 99.37 +/- 11.53 mm(3),p = .019) and left (109.71 +/- 14.94 mm(3)vs. 100.47 +/- 15.78 mm(3),p = .020) RN volumes. Cerebellar white matter lesion volume (WMLV) inversely correlated with both right and left RN volumes (r = -.333,p = .004 andr = -.298,p = .010, respectively), while no correlation was detected between RN volumes and mean cortical thickness, cerebellar gray matter lesion volume, and supratentorial WMLV (right RN:r = -.147,p = .216; left RN:r = -.153,p = .196). Right, but not left, RN volume inversely correlated with midbrain WMLV (r = -.310,p = .008), while no correlation was observed between whole brainstem WMLV and either RN volumes (right RN:r = -.164,p = .164; left RN:r = -.64,p = .588). Finally, left RN volume correlated with vermis VIIb (r = .297,p = .011) and right interposed nucleus (r = .249,p = .034) volumes. We observed RN atrophy in early RMS, likely resulting from anterograde axonal degeneration starting in cerebellar and midbrain WML. RN atrophy seems a promising marker of neurodegeneration and/or cerebellar damage in RMS.