Faculty Bibliography

Objectives: To compare relapse and sustained disability progression rates in previously stable MS patients who discontinued their disease- modifying therapy ('DMTs stoppers') and propensity-score matched MS patients who continued their therapy ('DMT stayers'). Background: It is not known how disease course in previously stable MS patients who discontinue DMT compares to disease course who stay on DMT. The large international MSBase Registry that prospectively follows MS patients in real-world clinical setting affords an opportunity for a prospective comparative study of patients who elected to stop DMT and those who did not. Methods: Patients were included in the 'DMT stoppers' group if they had diagnosis of MS; no relapses and no change in Expanded Disability Status Scale (EDSS) for >5 years at the time of DMD discontinuation; had continuous treatment with DMD for >3 years; were followed for >3 years after stopping DMD; did not restart DMD for >3 months after discontinuation. DMT stayers were matched 1:1 according to age, gender, disease duration, EDSS and proportion of time on prior treatment. Pairwise analysis of DMT stoppers and stayers from the international MSBase registry data was conducted using propensity-score matching. The groups were compared with respect to risk of relapses and sustained disability progression using Cox marginal model, using simultaneous censoring of the matched pair. Results: The cohort consisted of 140 DMT stoppers and 140 propensity-scored matched DMT stayers. 73% were women, mean age was 48 year; mean disease duration - 16 years; mean baseline ED

Objectives: To determine correlation between patient-reported disability as assessed with Patient Determined Disability Steps (PDDS) and clinician-rated Expanded Disability Status Scale (EDSS). Background: The EDSS is the 'gold standard' clinical assessment of disability in MS, but requires a trained examiner and is time-consuming. It would be valuable to have a patient-reported outcome measure for tracking disability that shows a high degree of concordance with EDSS and is easy to deploy in a busy clinic. Methods: Consecutive MS patients at an outpatient MS Center were asked to record their disability on the PDDS scale at routine visits, while a Neurostatus-certified physician assessed EDSS, confirmed MS diagnosis, and documented disease duration, relapse status and current disease-modifying therapy in a standardized fashion. Correlations between PDDS, EDSS and Functional System (FS) scores were computed for all patients using SAS software. EDSS-based MS Severity Score (MSSS) and PDDS-based Patient reported-MS severity Score (P-MSSS) were obtained using published reference Tables and compared. Results: 195 MS patients (age 46.4 +/-12.7 years, range=18-87; 73% female; disease duration 10.2+/- 7.4 years) were included. 82% of patients were on DMTs. 11 patients (5.6%) had a relapse at the time of the visit. Mean PDDS was 2.2 +/-2.4, range 0-7. Mean EDSS was 3.1 +/-2.3, range 0-9. PDDS strongly correlated with the EDSS (r=0.89, p< 0.0001) and P-MSSS correlated with MSSS (r=0.83, p< .0001). PDDS scores differed from the EDSS by 2 points or more in only 7 patients (3.6%). PDDS/EDSS correlation were similar among patients with and without obligate ambulatory assistance (r=0.62 for EDSS< 6 group and r= 0.56 for EDSS>5.5 group) and remained highly significant in patients with a relapse (r=0.84, p< .001). PDDS and EDSS showed strong correlation with pyramidal score (r=0.86 for PDDS and r=0.84 for EDSS) and bladder score (r=0.70 for PDDS and r=0.66 for EDSS); weak-to-moderate correlation (r from 0.3 to 0.6) with cerebellar, brainstem, sensory and cognition FS scores, and no correlation (r< 0.02) with vision score. Conclusions: The single-question PDDS is a reliable, highlyefficient and cost-effective tool for disability assessment in clinical and research settings that shows excellent correlation with the 'gold standard' EDSS

OBJECTIVE: The analysis of the MR phase provides additional information on the tissue microstructure. In multiple sclerosis (MS) lesions phase alterations may reflect different stages of inflammatory activity. Here we investigated lesion morphology in MS patients with short and long disease duration on T2* weighted, phase, magnitude and susceptibility weighted imaging (SWI) at 7 Tesla (T). METHODS: 17 MS or clinically isolated syndrome patients with short (<60 months) and 11 with long (>60 months) disease duration underwent 7T MRI. Lesions were subsequently analyzed side-by-side with regard to morphology and visibility on T2* weighted, SWI, magnitude and SWI-filtered phase images. RESULTS: 126 of 192 T2* weighted lesions (65.6%) were characterized by a phase alteration pattern, and hence could be differentiated on phase images. In detail, a significantly reduced proportion of lesions showing phase alterations was detectable in patients with longer disease duration (mean+/-SD 51+/-37%, range 0-100%) compared to patients with short disease duration (mean+/-SD 90+/-19.5%, range 50-100%, p = 0.003). CONCLUSION: This cross-sectional study identified different patterns of phase changes in lesions of MS patients with short and long standing disease. Longitudinal studies are warranted to prove that MR phase imaging is useful in determining the activity and the developmental stage of individual MS plaques.

Neuromyelitis optica spectrum disorders, or neuromyelitis optica (NMO), is an autoimmune disease of the central nervous system that must be distinguished from multiple sclerosis. Therapeutic approaches to relapse prevention in NMO include immunosuppressants and monoclonal antibodies. Rituximab, a monoclonal antibody that targets CD20 antigen expressed on the surface of pre-B, mature B-lymphocytes and a small subset of T-lymphocytes, has been widely used for the treatment of NMO. In this review, we aim to summarize global experience with rituximab in NMO. We identified 13 observational studies that involved a total of 209 NMO patients treated with rituximab. Majority of rituximab-treated patients evidenced stabilization or improvements in their disability scores compared to pre-treatment period and 66% of patients remained relapse-free during treatment period. Monitoring rituximab treatment response with CD19+ or CD27+ cell counts appears to improve treatment outcomes. We offer clinical pointers on rituximab use for NMO based on the literature and authors’ experience, and pose questions that would need to be addressed in future studies.