A standardised definition of progression independent of relapse activity in multiple sclerosis

Abstract

Introduction: Many people with multiple sclerosis experience a rapid progression following the attainment of moderate disability. Identifying the clinical variables and the underpinning biology of Rapidly Disabling MS (RDMS) could allow for better prognosis and management. Objectives/Aims: To describe the clinical and pathological features of relapse-onset MS who later experienced Non-Disabling MS (NDMS), Disabling MS (DMS) or RDMS. Methods: A longitudinal patient cohort was selected from the UKMS Register with ⩾3 submissions of the Multiple Sclerosis Impact Scale 29-Physical sub-score (MSIS29-Phys) over minimum 2-year period and diagnosis of relapsing-onset MS. Disability trajectories were linearly modelled from the first MSIS29-Phys score in the range 30-40. NDMS (n=697), DMS (n=870) and RDMS (n=397) groups were identified based on correlation coefficients. A separate SPMS autopsy cohort (n=60, mean age of onset= 30.2, age progression= 41.3, age died 59), sub-grouped on the time taken from the onset of progression to the time of first recorded use of a wheelchair. The extent of neurodegeneration, demyelination, and compartmentalised inflammation from six brain areas per case was recorded. Results: From the UKMS Register: Average age now (55.5/58.6/56 for NDMS/DMS/RDMS, respectively); age at onset (33.7/34.6/33). Median MSIS29-Phys first score (35.0 all groups), last score (25/ 46.7/61.7, p<.05). Body-mass-index at diagnosis was higher in DMS and RDMS (BMI, 25.6/29.6/29.5, p<0.5), and fewer had a university degree (49.6/44.1/36.3%), in comparison to NDMS. The proportion of patients receiving high efficacy treatment was similar (33/29.5/33.9% of those on treatment). At autopsy, RDMS vs DMS (time from SPMS to wheelchair= 1.2 vs 11.7yrs, p<.0001), differed in terms of neuron density (HUC+ neurons/mm 2) in the thalamus and basal pons (reduced by 21.5 to 37.3%, p<.0001). Total lesion area was more extensive in RDMS (cerebellar white matter, 4.9 vs 1.0%; pons, 13.2 vs 3.1%; p<.03). Perivascular and leptomeningeal