CSF B-cell expansion in opsoclonus-myoclonus syndrome: a biomarker of disease activity.

Lack of a biomarker of disease activity has hindered the therapy of childhood opsoclonus-myoclonus syndrome (OMS), which is purported to be mediated humorally. To determine if the cerebrospinal fluid (CSF) B lymphocyte, which may traffic into the central nervous system (CNS) to produce antibody locally, is one such biomarker, B lymphocytes were immunophenotyped in the CSF and blood of 56 children with OMS and 26 pediatric controls by dual-laser flow cytometry. Neurological severity was rated blindly from videotapes using a validated 12-item motor evaluation scale. Children with OMS manifested a 4- to 7-fold higher percentage of total B-cells in CSF (P < 0.0001), including CD5(+) (P = 0.001) and CD5(-) (P = 0.0004) B-cell subsets, compared with controls, in whom the percentages were negligible and unchanging with age. CSF expansion of both B-cell subsets increased with disease severity and decreased with disease duration (P </= 0.0001, ANOVA). Previous treatment with conventional immunotherapies, chemotherapy, or tumor resection had not normalized B-cell percentages in those with lingering symptoms. These studies reveal that CSF B-cell expansion in OMS is characteristic and often persistent. Presence of the autoreactive CD5(+) B-cell subset and correlations with neurological severity and disease duration suggest CSF B-cell expansion is a biomarker of disease activity and possible target for B-cell-specific therapy. Immunophenotyping of CSF lymphocytes by flow cytometry yields valuable clinical information missed by routine studies and allows crucial treatment decisions to be made rapidly. Copyright 2004 Movement Disorder Society