Faculty Bibliography

BACKGROUND:Delayed-release dimethyl fumarate (DMF) has demonstrated robust efficacy in treating patients with relapsing-remitting multiple sclerosis. Decreases in absolute lymphocyte count (ALC) are a well-known pharmacodynamic effect of DMF treatment, but lymphocyte recovery dynamics are not well characterized after discontinuation of DMF. METHODS:Data sources included the Biogen DMF integrated clinical trial data set, a retrospective US chart abstraction study, and data from MSBase. We assessed rate and time course of lymphocyte reconstitution after DMF discontinuation. RESULTS:/L was 12-18 months vs 2-3 months in patients with lymphopenia persisting <6 months. CONCLUSIONS:The majority of patients who discontinued DMF due to lymphopenia experienced ALC reconstitution within 2-4 months following DMF discontinuation. This may help guide clinicians in managing patients who develop lymphopenia during DMF treatment. Prolonged lymphopenia on DMF treatment is associated with slow lymphocyte recovery after DMF discontinuation.

BACKGROUND:In patients treated with dimethyl fumarate, absolute lymphocyte count decline typically occurs during the first year and then plateaus; early drops have been associated with the development of severe prolonged lymphopenia. OBJECTIVE:We investigated the effect of dimethyl fumarate on absolute lymphocyte counts and CD4+/CD8+ T cells in patients with relapsing-remitting multiple sclerosis treated with dimethyl fumarate in routine practice. METHODS:Lymphocyte data were collected via medical chart abstraction. Primary endpoint: change from baseline in absolute lymphocyte count and CD4+/CD8+ counts at 6-month intervals following dimethyl fumarate initiation. RESULTS:/l) decreased by ∼39% (95% confidence interval: -41.1 to -37.2) by month 6 and 44% (95% confidence interval: -46.6 to -42.1) by month 12. CD4+ and CD8+ T-cell subsets strongly correlated with absolute lymphocyte count, with greater decreases from baseline to 6 months vs 6-12 months, and in CD8+ vs CD4+ T cells. Prior natalizumab was not a risk factor for lymphopenia. CONCLUSION/CONCLUSIONS:Dimethyl fumarate-associated decline in absolute lymphocyte count in the first 12 months correlated with decline in CD4+ and CD8+ T cells and was independent of prior natalizumab. Absolute lymphocyte count monitoring continues to be an effective strategy to identify patients at risk of prolonged lymphopenia.

OBJECTIVE:To determine the influence of self-reported Black African and Latin American identity on peripheral blood antibody-secreting cell (ASC) frequency in the context of relapsing-remitting MS. METHODS:In this cross-sectional study, we recruited 74 subjects with relapsing-remitting MS and 24 age-, and self-reported ethno-ancestral identity-matched healthy donors (HDs) to provide peripheral blood study samples. Subjects with MS were either off therapy at the time of study draw or on monthly natalizumab therapy infusions. Using flow cytometry, we assessed peripheral blood mononuclear cells for antibody-secreting B-cell subsets. RESULTS:subsets, were among those significantly increased. CONCLUSION:The enhanced peripheral blood plasmablast signature revealed among Black African or Latin American subjects with MS points to distinct underlying mechanisms associated with MS immunopathogenesis. This dysregulation may contribute to the disease disparity experienced by patient populations of Black African or Latin American ethno-ancestry.

Olivopontocerebellar atrophy is a rare neurodegenerative syndrome associated with 2 distinct disorders: multiple system atrophy and spinocerebellar ataxia. We present a case involving a 66-year-old man with adult-onset progressing cerebellar signs reflective of a cerebellar syndrome with no significant family history and unremarkable genetic testing for spinocerebellar ataxia. This case was found to be most consistent with sporadic olivopontocerebellar atrophy, which falls under the multiple system atrophy category. This diagnosis can be made using F-FDG PET/CT scanning and with MRI in some cases. However, in this case, relatively new PET/CT quantification and parametric imaging software was used for analysis, CortexID Suite.