Onset of Progressive Motor Impairment in Patients with Critical CNS Demyelinating Lesions (4405)

Objective: Compare age at onset of progressive motor impairment in patients with “critical” lesion associated PSS, PPS, and PUHMS. Background: Progressive motor impairment in MS is associated with patient age but poorly correlated with brain lesion burden. Demyelinating lesion/s along the corticospinal tract (“critical” lesions), determine progressive motor impairment in patients with progressive solitary sclerosis (one lesion, PSS), progressive motor impairment with highly restricted lesion burden (2–5 lesions, progressive “paucisclerotic” MS (PPS)), and progressive unilateral hemiparetic MS with unlimited CNS lesion burden (PUHMS). Design/Methods: Inclusion criteria were: Mayo Clinic patients with progressive motor impairment ≥1 year, attributable to a critically located lesion/s with: a total of 1 CNS demyelinating lesion (PSS), 2–5 lesions (PPS), or >5 lesions with unilateral hemiparesis or monoparesis fulfilling 2017 McDonald criteria (PUHMS). Multiple brain and spinal cord MRI were reviewed, with lesions considered as unequivocally demyelinating. Results: 135 patients were included (PSS n=33, PPS n= 56 and PUHMS n= 46). Primary progressive disease course was seen in 82% PSS, 61% PPS and 52% PUHMS with the remainder having relapse associated onset. Median age at onset of progressive motor impairment was younger in PSS (49 years; range 24–73) and PPS (50 years; range 30–64) than in PUHMS (54 years; range 39–77) (p=0.02, p=0.003 respectively). Median age at onset of motor progression did not differ between primary progressive and secondary progressive clinical course nor comparing patient groups with 1–10, 11–20, and >20 brain demyelinating lesions (55, 54 and 53 years respectively; p=0.44). Conclusions: Onset of motor progression is paradoxically earlier in patients with critical demyelinating lesions and lower total CNS lesion burden (progressive solitary sclerosis and progressive paucisclerotic MS) than in progressive unilateral hemiparetic MS. The “critical” demyelinating lesion rather than brain MRI lesion burden is the major contributor to onset of motor progression in these cohorts. Disclosure: Dr. Kassa has nothing to disclose. Dr. Sechi has nothing to disclose. Dr. Flanagan has received research support from Medimmune/Viela Bio. Dr. Kaufmann has received research support from SpineThera. Dr. Kantarci has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis and Biogen. Dr. Kantarci has received research support from Biogen, the Multiple Sclerosis Society, the Mayo Foundation, and the Hilton Foundation. Dr. Weinshenker has received personal compensation from Alexion, Chugai/Roche, MedImmune, Mitsubishi Tanabe Pharma, Viela Bio. Dr Weinshenker has received research support from Alexion Pharmaceuticals, Terumo BCT.Dr. Mandrekar has nothing to disclose. Dr. Schmalstieg has nothing to disclose. Dr. Paz Soldan has received research support from Biogen. Dr. Keegan has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Publishing royalties from Cambridge University Press for “Common Pitfalls in Multiple Sclerosis and CNS Demyelinating Diseases”. Dr. Keegan has received research support from Biogen.