Faculty Bibliography

BACKGROUND: Neuromyelitis optica (NMO) is an uncommon, life-threatening inflammatory demyelinating disorder. Recently, much has become known about its immunopathogenesis. However, optimal treatments, with expected outcomes, have not been established. OBJECTIVE: To evaluate the use and efficacy of rituximab for treating NMO. DESIGN: Retrospective multicenter case series of NMO patients treated with rituximab. SETTING: Seven tertiary medical centers in the United States and England. PATIENTS: Twenty-five patients (including 2 children), 23 of whom experienced relapses despite use of other drugs before rituximab. Extended follow-up of 7 previously reported patients is included. INTERVENTIONS: Infusions of rituximab at median intervals of 8 months. MAIN OUTCOME MEASURES: Annualized relapse rate and disability (expressed as Expanded Disability Status Scale score). RESULTS: At a median follow-up of 19 months, the median annualized posttreatment relapse rate was lower than the pretreatment rate (0 [range 0-3.2] vs 1.7 [range, 0.5-5] relapses, P < .001). Disability improved or stabilized in 20 of 25 patients (80%, P = .02). Two patients died during the follow-up period, 1 owing to a brainstem relapse and 1 owing to suspected septicemia. Infections were reported in 20% of patients. CONCLUSIONS: In NMO, treatment with rituximab appears to reduce the frequency of attacks, with subsequent stabilization or improvement in disability.

BACKGROUND: we sought to assess how impairment (physiological/psychological) and disability (social/environmental) are associated with physical and leisure/recreation activity levels and quality of life (QOL) in people with moderate/severe multiple sclerosis (MS). We conducted a cross-sectional survey at the MS Comprehensive Care Center, Stony Brook University Hospital, Stony Brook, NY, of a convenience sample of 43 people (50 eligible) with MS and Expanded Disability Status Scale scores of 6.0 to 8.0. The main outcome measures were QOL measured by MSQOL-54, physical activity measured by Physical Activity Disability Scale, and leisure/recreation activity measured by Nottingham Leisure Questionnaire. We analyzed the canonical correlations among physical and leisure/recreation activity levels and (1) impairment and (2) QOL. RESULTS: higher levels of physical and leisure/recreation activity were associated with lower levels of apathy and depression and higher levels of cognition, self-efficacy, and QOL (physical and mental). Major barriers reported included fatigue, lack of motivation, and cost. CONCLUSION: impairments and social/environmental disabilities create barriers to physical and leisure/recreation activity. Additional research is needed to determine, for people with MS, what supports might increase participation in physical and leisure/recreation activities and whether this increase yields improved QOL.

OBJECTIVES: Pediatric-onset multiple sclerosis offers a unique window into early targets and mechanisms of immune dysregulation. It is unknown whether heightened T-cell reactivities documented in adult patients, to both target-organ and environmental antigens, emerge in parallel or develop as early or late events. Our objectives were to determine the presence, pattern, and specificity of abnormal T-cell reactivities to such antigens in the earliest stages of the multiple sclerosis process. METHODS: Peripheral T-cell proliferative responses to self-, dietary, and control antigens were blindly evaluated in a large cohort of well-characterized children (n = 172) with central nervous system (CNS) inflammatory demyelination (n = 63), recent-onset type 1 (insulin-dependent) diabetes mellitus (T1D; n = 41), nonautoimmune neurological conditions (n = 39), and healthy children (n = 29). RESULTS: Children with inflammatory demyelination, CNS injury, and T1D exhibited heightened T-cell reactivities to self-antigens, and these responses were not strictly limited to the disease target organs. Children with autoimmune disease and CNS injury also exhibited abnormal T-cell responses against multiple cow-milk proteins. Responses to specific milk epitopes distinguished T1D from inflammatory demyelination and other neurological diseases. INTERPRETATION: Abnormal T-cell reactivities to self- and environmental antigens manifest in the earliest clinical stages of inflammatory demyelination and T1D. The pattern of heightened T-cell reactivities implicates both shared and distinct mechanisms of immune dysregulation in the different autoimmune diseases. Abnormal T-cell responses in children with tissue injury challenge the prevailing view that CNS autoreactive cells inherently mediate the disease in early multiple sclerosis.