Background: The Multiple Sclerosis Severity Score (MSSS) is a widely used measure of the disability progression rate. However, the global MSSS may not be the best basis for comparison between all patient groups. Objective: We evaluated sex-specific and onset phenotype–specific MSSS matrices to determine if they were more effective than the global MSSS as a basis for comparison within these subsets. Methods: Using a large international dataset of multiple sclerosis (MS) patient records and the original MSSS algorithm, we constructed global, sex-specific and onset phenotype–specific MSSS matrices. We compared matrices using permutation analysis. Results: Our final dataset included 30,203 MS cases, with 28.9% males and 6.5% progressive-onset cases. Our global MSSS matrix did not differ from previously published data ( p > 0.05). The progressive-onset-specific matrix differed significantly from the relapsing-onset-specific matrix ( p < 0.001), with lower MSSS attributed to cases with the same Expanded Disability Status Score (EDSS) and disease duration. When evaluated with a simulation, using an onset-specific MSSS improved statistical power in mixed cohorts. There were no significant differences by sex. Conclusion: The differences in the disability accrual rate between progressive- and relapsing-onset MS have a significant effect on MSSS. An onset-specific MSSS should be used when comparing the rate of disability progression among progressive-onset cases and for mixed cohorts.

Objective: We aimed to investigate the alteration of differential WBC counts, apoptosis-associated speck-like protein (ASC) and B-cell lymphoma protein (BCL-6) in Egyptian multiple sclerosis (MS) patients in response to disease modifying therapy (DMT) Methods: The present study was conducted on a total of 58 relapsingremitting MS (RRMS) patients who were classified into 21 untreated naïve patients and 37 treated patients as well as 30 healthy individuals. Assessment of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and monocyte-lymphocyte ratio (MLR) was performed. Peripheral blood mononuclear cells (PBMCs) were isolated and cultured in the presence of lipopolysaccharide (LPS) for the detection of inflammasome adaptor protein ASC and BCL-6 using ELISA. Results:The results revealed that untreated RRMS patients showed a significant increase in neutrophils and BCL-6 levels together with a marked decrease in monocytes and MLR compared to both treated patients and healthy controls. A marked increase in ASC levels was observed in all patients compared to healthy controls where ASC was negatively correlated with BCL-6. We also demonstrated that both NLR and ASC were positively correlated with IgG index. Conclusions: It can be concluded that altered peripheral blood cells, ASC and BCL-6 may have vital roles in RRMS pathogenesis suggesting their possible diagnostic and therapeutic potentials in RRMS.

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