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

BACKGROUND: Growing evidence suggests an association between adolescent obesity and increased risk of multiple sclerosis (MS). OBJECTIVE: The objective of this paper is to investigate whether weight or body mass index (BMI) in adolescence and young adulthood was associated with age at MS symptom onset. METHODS: Our cohort is comprised of a sub-group of 184 women enrolled in the New York State MS Consortium registry. Individuals were asked to recall their weight at the time of first menstruation and at age 25. BMI was calculated accordingly for age 25. Regression analyses were carried out to investigate the association between weight or BMI and age at onset. RESULTS: Weight at menarche was significantly related to younger age at symptom onset (beta = -0.073, p = 0.001). These results were also found at age 25 for weight (beta = -0.080, p < 0.001) and BMI (beta = -0.448, p = 0.001). Significantly earlier disease onset (26.9 years +/-9.9) was observed in individuals who were overweight at 25 compared to those who were not overweight (32.1 years +/-9.2, p = 0.006). CONCLUSIONS: Women who reported higher weight in adolescence and BMI in early adulthood were younger at MS onset. Future research should investigate whether there is a causal link between body weight and MS, as prevention lifestyle and dietary interventions could be implemented.

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.

OBJECTIVE: To describe the expanding clinical spectrum of a recently described hereditary leukoencephalopathy, hypomyelination with brainstem and spinal cord involvement and leg spasticity, which is caused by mutations in the aspartyl tRNA-synthetase encoding gene DARS, including patients with an adolescent onset. METHODS: Three patients with mutations in DARS were identified by combining MRI pattern recognition and genetic analysis. RESULTS: One patient had the typical infantile presentation, but 2 patients with onset in late adolescence had a disease mimicking an acquired inflammatory CNS disorder. Adolescent-onset patients presented with subacute spastic paraplegia and had positive response to steroids. They had only minor focal supratentorial white matter abnormalities, but identical spinal cord changes involving dorsal columns and corticospinal tracts. Clinical presentation included subacute spastic paraplegia with partial improvement on steroids. CONCLUSIONS: Focal T2 hyperintense white matter changes on brain MRI in combination with spinal cord signal abnormalities usually suggest acquired inflammatory conditions such as multiple sclerosis, especially in the context of relapsing course and a positive response to steroid treatment. Adolescents with mutations in DARS can present with a comparable clinical picture, broadening the clinical spectrum of hypomyelination with brainstem and spinal cord involvement and leg spasticity.

Limited data suggest that multiple sclerosis (MS) in Latin America (LA) could be less severe than in the rest of the world. The objective was to compare the course of MS between LA and other regions. METHODS: Centers from 18 countries with >20 cases enrolled in the MSBase Registry participated. Patients with MS with a disease duration of >1 year and <30 years at time of EDSS measurement were evaluated. The MS Severity Score (MSSS) was used as a measure of disease progression. Comparisons among regions (North America, Europe, Australia and LA), hemispheres and countries were performed. RESULTS: A total of 9610 patients were included. Patients were from: Europe, 6290 (65.6%); North America, 1609 (16.7%); Australia, 1119 (11.6%); and LA, 592 (6.1%). The mean MSSS in patients from LA was 4.47 +/- 2.8, 4.53 +/- 2.8 in North America, 4.51 +/- 2.8 in Europe and 4.49 +/- 2.7 in Australia. Mean MSSS in the northern hemisphere was 4.51 +/- 1.6 compared to 4.48 +/- 1.9 in the southern hemisphere. No differences were found for MSSS among hemispheres (p = 0.68), regions (p = 0.96) or countries (p = 0.50). CONCLUSIONS: Our analyses did not discover any difference in mean MSSS among patients from different regions, hemispheres or countries.