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

Mov Disord. 2004 Jul;19(7):770-777. doi: 10.1002/mds.20125.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antigens, CD19 / cerebrospinal fluid*
  • Antigens, CD19 / immunology*
  • B-Lymphocytes
  • Biomarkers
  • Brain Neoplasms / complications
  • CD5 Antigens / cerebrospinal fluid*
  • CD5 Antigens / immunology*
  • Child
  • Child, Preschool
  • Female
  • Flow Cytometry
  • Humans
  • Immunophenotyping
  • Infant
  • Lymphocyte Subsets
  • Male
  • Neuroblastoma / complications
  • Paraneoplastic Syndromes, Nervous System / cerebrospinal fluid*
  • Paraneoplastic Syndromes, Nervous System / complications
  • Paraneoplastic Syndromes, Nervous System / immunology*
  • Severity of Illness Index
  • Videotape Recording


  • Antigens, CD19
  • Biomarkers
  • CD5 Antigens