Effect of low-dose cyclophosphamide, ACTH, and IVIG combination immunotherapy on neuroinflammation in pediatric-onset OMS: A retrospective pilot study.

INTRODUCTION: Flow cytometric cerebrospinal fluid (CSF) lymphocyte subset analysis has improved the diagnosis of neuroinflammation and identified multiple markers of inflammation in opsoclonus-myoclonus syndrome (OMS). The aim of this exploratory, retrospective study was to analyze the effect of immunotherapy on these markers to determine which agents are disease modifying.

METHODS: Cross-sectional immunological observations were made in an IRB-approved case-control study, and patients were treated empirically. Ten different CSF lymphocyte subpopulations from 18 children with persistent OMS had been measured by flow cytometry before and after clinical treatment with cyclophosphamide/ACTH/IVIG combination (n = 7) or ACTH/IVIG alone (n = 11). Clinical severity of OMS was scored from videotapes by a blinded observer using the OMS Evaluation Scale.

RESULTS: Only cyclophosphamide combination therapy (mean dose 26 ± 3 mg/kg or 922 ± 176 mg/m2 x 6 cycles) significantly decreased the percentage of CSF B cells. The mean reduction was 65%, with CSF B cell frequency normalized at 7-8 months in 70%. Other abnormalities of the CSF immunophenotype, such as the low CD4/CD8 T cell ratio, persisted, and there were no therapeutic changes in T cell activation/maturation markers. Effects on relative and absolute size of PBMC subsets were similar. Clinical improvement was 70% and 55% in respective treatment groups. The relapse rates of the two groups did not significantly differ.

DISCUSSION: The main effect of cyclophosphamide combination therapy on neuroinflammation in OMS was moderate reduction in CSF B cell expansion. Though exploratory, it may provide a steroid sparer option in partially-responsive OMS.