Medulla Oblongata Atrophy in Early Stage Multiple Sclerosis

Objective: To investigate medulla oblongata (MO), pons and mesencephalon atrophy on brain 3D T1-weighted images in early stage patients with Multiple Sclerosis (MS) using a fully-automated deep learning-based segmentation approach. Background: Brainstem (BS) involvement is regarded as a bad prognostic sign and can limit life expectancy in MS. In contrast to cortical, subcortical and spinal cord atrophy, BS atrophy has not been systematically investigated in early stage MS. Design/Methods: A novel, fully-automated deep learning-based segmentation approach (Sander et al. 2019) was used to assess BS volumes from high-resolution 3D T1w MPRAGE images obtained at either a 3T Skyra (24.4%) or 1.5T Avanto Scanner (75.6%) (Siemens Healthineers) in 182 patients with early stage MS (mean age 37.7 years, SD 11.2, 61% women, median EDSS 1.75, IQR 1.5, median disease duration 1.4 years, range 0.01–3.98 years) and 80 age- and sex-matched healthy controls (HC; mean age 37.7 years, SD 13.3, 60% women) as part of the ongoing Swiss MS cohort-study. BS function was assessed using the Neurostatus-EDSS BS Functional System Score. Results: Compared to HC, patients showed significant MO volume reductions (p=0.004; % difference 4.96%) in absence of significant atrophy of the mesencephalon and pons. This difference was visible in patients with (p=0.001) and without (p=0.016) clinical BS involvement (adjusted for age and sex). Even the patients with the shortest disease duration below the 25th percentile (range 0.01–0.72 years) showed a significant MO atrophy compared to HC (p=0.024, adjusted for age and sex). Conclusions: Isolated MO atrophy occurs very early in MS in absence of significant pons and mesencephalon atrophy. This observation is independent of clinical BS involvement. Further longitudinal studies are necessary to investigate its role as a marker for disease course monitoring and outcome prediction. Disclosure: Dr. Sander has nothing to disclose. Dr. Horvath has nothing to disclose. Dr. Pezold has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Advanced Osteotomy Tools AG (Basel, CH). Dr. Amann has nothing to disclose. Dr. Andermatt has nothing to disclose. Dr. Yaldizli has nothing to disclose. Dr. Wuerfel has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with CEO of the MIAC AG, also fees from Actelion, Biogen, Sanofi Genzyme, Novartis and Roche. Dr. Kappos has received research support from Bayer, Biogen, Innosuisse, Novartis, the Swiss MS Society, the Swiss National Research Foundation, and the European Union.Dr. Granziera has nothing to disclose. Dr. Gobbi has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis, Biogen, Merck, Almirall, Roche, TEVA.Dr. Kuhle has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Genzyme, Novartis, Roche, Teva, Merck. Dr. Kuhle has received research support from ECTRIMS Research Fellowship Programme, University of Basel, Swiss MS Society, Swiss National Research Foundation (320030_160221), Bayer, Biogen, Genzyme, Celgene, Novartis, Roche, Teva, Merck.Dr. Cattin has nothing to disclose. Dr. Schlaeger has received research support from Biogen.