Early red nucleus atrophy in relapse-onset multiple sclerosis

Monica Margoni, Davide Poggiali, Sofia Zywicki, Martina Rubin, Andrea Lazzarotto, Silvia Franciotta, Maria Giulia Anglani, Francesco Causin, Francesca Rinaldi, Paola Perini, Massimo Filippi, Paolo Gallo

Research output: Contribution to journalArticlepeer-review


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 mm3 vs. 99.37 ± 11.53 mm3, p =.019) and left (109.71 ± 14.94 mm3 vs. 100.47 ± 15.78 mm3, 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.

Original languageEnglish
Pages (from-to)154-160
Number of pages7
JournalHuman Brain Mapping
Issue number1
Publication statusPublished - Jan 2021


  • cerebellum
  • MRI
  • red nucleus

ASJC Scopus subject areas

  • Anatomy
  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Clinical Neurology


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