The findings indicate that the use of a MS severity score (Ped-MSSS) model may provide an alternative to EDSS scoring, which has been shown to be lower in pediatric disease, in clinical assessment of disease severity and disability accrual.
Tanuja Chitnis, MD
Data from a retrospective analysis demonstrated that persons with pediatric-onset multiple sclerosis (POMS) exhibit lower Expanded Disability Status Scale (EDSS) scores compared to persons with adult-onset MS. Furthermore, the findings suggest that the pediatric MS severity score (Ped-MSSS) represents an alternative method of evaluating disease severity in patients with POMS.
Corresponding author Tanuja Chitnis, MD, professor of neurology, Harvard University, and colleagues aimed to characterize disease severity and distribution of disability in POMS using a multicenter approach that included 873 persons with POMS, and comparing their analysis to previously published data by Roxburgh et al. in adults with MS. EDSS scores of 2.0, 3.0, and 6.0 were found in 52%, 19.4%, and 1.5% of all patients, respectively, at any time point.
In the POMS cohort, an EDSS of 2.0, 3.0, and 6.0 corresponded to decile scores of 8.00/9.46/9.94, 7.86/9.39/9.91, and 7.32/9.01/9.86 at 2, 5, and 10 years after diagnosis, respectively. Notably, the lowest decile score at an EDSS of 2.0 in the cohort was 6.94. By comparison, in the adult data published by Roxburgh et al., decile scores of 5.24/7.27/9.59, 3.90/5.79/8.83, and 2.34/3.79/7.39 were reported at 2, 5, and 10 years post-onset, respectively.
“At EDSS milestones of 2.0, 3.0 and 6.0, our cohort differed greatly from established adult data, with much higher Ped-MSSS scores compared to MSSS scores at similar disease duration timepoints. This finding is consistent with data emerging from smaller and more homogenous cohorts of patients with POMS,” Chitnis and colleagues concluded.
Patients were also stratified by the number of years from first symptoms of MS to EDSS assessment, and Ped-MSSS was calculated using criteria developed by Roxburgh et al. in 2005. When comparing Ped-MSSS and previously published adult MSSS scores, slower progression was noted in Ped-MSSS with increasing gaps between higher EDSS score and years after diagnosis.
Both EDSS score and Ped-MSSS score 2 years after diagnosis were predictive of the most recent respective EDSS or Ped-MSSS score in patients with more than 5 years of follow up (EDSS, r
= 0.52; Ped-MSSS, r
= 0.50). Chitnis at al. also noted that linear regression models comparing EDSS scores at 5 years to Ped-MSSS declie at 5 years indicated that notable predictors of disease progression in both EDSS were “ever having a motor relapse” (EDSS effect, 0.41; 95% CI, 0.01–0.80; Ped-MSSS effect, 1.20; 95% CI, 0.23–2.17) and EDSS at year 1 (EDSS effect, 0.35; 95% CI, 0.20–0.51; Ped-MSSS effect, 0.63; 95% CI, 0.25–1.02), respectively.
Of the 873 patients included in the study, 500 had a Symbol Digit Modalities Test (SDMT) analysis at any time point. The average number of SDMT administrations was 2.8 (standard deviation [SD], 1.9; range, 1–11). There were 1403 SDMT recordings with a mean value of 55.5 (SD, 14.2) and a modest correlation between SDMT score and EDSS at 5 years (r
Researchers also noted that there was a statistically significant inverse trend when the EDSS cerebral functional score (FS) was compared to the SDMT data, indicating that lower SDMT scores matched higher cerebral FS scores across all EDSS levels (r
Chitnis and colleagues concluded, “The Ped-MSSS represents an alternative, and arguably more sensitive, method of evaluating disease severity in patients with POMS. This is the first study of its kind to assess disease severity and disability in the context of disease duration in POMS, and the model studied has the potential to more sensitively assess changes in disease state and/or response to therapeutic intervention in this unique population.”
Santoro J, Waltz M, Aaen G, et al. Pediatric Multiple Sclerosis Severity Score in a Large US Cohort. Neurology. Published online July 20, 2020. doi: 10.1212/WNL.0000000000010414.