Can Certain Baseline Characteristics in Patients with Stiff Person Syndrome (SPS) Predict Disease Burden and Functional Outcomes?

Objective: To identify if baseline characteristics such as phenotype, body-region involvement and others can predict disease burden and functional-outcomes in patients with Stiff-Person Syndrome (SPS). Background: SPS is a neuroimmunological disease that presents with various manifestations and can cause significant disability. It is not well-known whether there are potential risks-factors for disease-burden and future disability in SPS; especially factors that are present early on that give insight into worse prognosis. To identify if baseline characteristics such as clinical phenotype and body-region involvement help determine disease-burden and predict future disability/functional-outcomes in patients with Stiff-Person Syndrome(SPS). Design/Methods: Retrospective medical record review from 1997 to 2019 at Johns Hopkins. Clinical phenotypes were assigned by review of history and examination; classic SPS, stiff-limb syndrome, SPSplus( classic SPS+cerebellar/brainstem findings), pure cerebellar(no musculoskeletal symptoms/signs), and progressive encephalomyelitis with rigidity and myoclonus(PERM). Initial symptom presentation(stiffness;spasms;cerebellar;brainstem) and stiffness location(limb;trunk/torso;face) were also recorded. We calculated modified-Rankin Scale(mRS) scores for each clinical visit and a subset had timed 25-foot walk(T25FW) available. We calculated if SPS phenotype or initial symptoms predicted change in mRS or T25FW over time using mixed effects models. Results: We identified 186 patients(average age of onset:42y[SD:14.4];73% female;27% non-white) with SPS-spectrum disorders with moderate-disability(median mRS=3.0; IQR:2–3). Both initial brainstem/cerebellar symptoms(iBSCeSym) and SPS-plus/cerebellar phenotypes were associated with high-mRS at baseline(mean difference in mRS for iBSCeSym:0.51; 95%CI:0.13–0.88;p=0.009; SPS-plus:0.42; 95%CI:0.01–0.82;p=0.05; cerebellar:0.62; 95%CI:0.03–1.25;p=0.04). iBSCeSym and SPS-plus phenotypes were associated with slower-walking speeds (n=134; iBSCeSym:63% slower; 20.5–221.1%;p=0.002; SPS-plus:64% slower;18.1–227.1%;p=0.004). In longitudinal-analyses, SPS-phenotypes and initial symptoms did not predict change in mRS or T25FW. Conclusions: We describe a unique observation in the largest cohort of patients with SPS;SPS-plus/cerebellar phenotypes have greater disability at presentation compared to their counterparts. These findings suggest that disease phenotype and/or body-region involved may act as a biomarker for early disease-burden and emphasize the need for earlier diagnosis and considerations of implementing immune-therapies earlier. Disclosure: Dr. Mukharesh has nothing to disclose. Dr. Fitzgerald has nothing to disclose. Dr. Wang has nothing to disclose. Dr. Newsome has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Celgene, EMD Serono, Genentech, medDay Pharmaceuticals, and Gerson Lehrman Group.. Dr. Newsome has received research support from Biogen, Genentech.