Rituximab, IVIg, and Tetracosactide (ACTH1-24) Combination Immunotherapy ("RITE-CI") for Pediatric Opsoclonus-Myoclonus Syndrome: Immunomarkers and Clinical Observations

Neuropediatrics. 2018 Apr;49(2):123-134. doi: 10.1055/s-0037-1609038. Epub 2017 Dec 19.

Abstract

Opsoclonus-myoclonus syndrome (OMS) is a neuroinflammatory disorder with pervasive morbidity that warrants better treatments. Twelve children with moderate/severe OMS (total score 23 ± 6) who did not remit to multiple immunotherapies were evaluated for neuroinflammation in a case-control study using cerebrospinal fluid (CSF) lymphocyte subset analysis by flow cytometry, chemokine/cytokine analysis by enzyme-linked immunoadsorption assay (ELISA), and oligoclonal bands by immunofixation with isoelectric focusing. Observations made on empirical treatment with rituximab, IVIg, and tetracosactide combination immunotherapy (coined "RITE-CI") were analyzed. All of the patients tested for multiple inflammatory markers were positive; 75% had ≥3 CSF markers. Fifty percent had CSF oligoclonal bands; 58%, B cell expansion; and 50 to 100%, elevated concentrations of multiple chemokines and neuronal/axonal marker neurofilament light chain. After RITE-CI, total score dropped significantly in the group (-85%, p < 0.0001) from moderate to trace, and by 2 to 4 severity categories in each patient. The 24-week schedule was well tolerated and clinically effective for moderate or severe OMS, as were other schedules. RITE-CI is feasible and effective as rescue therapy and presents an initial option for children with moderate/severe OMS. Though preliminary, the schedule can be adjusted to patient severity, propensity for relapse, and other factors.

MeSH terms

  • Child
  • Child, Preschool
  • Cosyntropin / therapeutic use*
  • Cytokines / metabolism
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Hormones / therapeutic use*
  • Humans
  • Immunization, Passive / methods
  • Immunoglobulins, Intravenous / therapeutic use*
  • Immunologic Factors / therapeutic use*
  • Infant
  • International Cooperation
  • Male
  • Opsoclonus-Myoclonus Syndrome / therapy*
  • Rituximab / therapeutic use*
  • Severity of Illness Index
  • Treatment Outcome

Substances

  • Cytokines
  • Hormones
  • Immunoglobulins, Intravenous
  • Immunologic Factors
  • Cosyntropin
  • Rituximab