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 and r = −.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.