Effect of Increased Immunosuppression on Developmental Outcome of Opsoclonus Myoclonus Syndrome (OMS)

Abstract

Opsoclonus myoclonus syndrome (OMS) produces long-term cognitive, behavioral, and motor deficits. Objective was to see if more aggressive treatment improved outcome. Assessment included opsoclonus myoclonus syndrome rating, developmental/cognitive and motor assessment, and adaptive behavior. Fourteen subjects completed testing. Nine had neuroblastoma. Onset was at 10 to 35 months; onset to diagnosis: 2 days to 14 months, and onset to first treatment: 5 days to 15 months. Initial treatment was corticotropin (12), oral steroids (3), plus intravenous immunoglobulin in all. Ten received rituximab, 5 cyclophosphamide. Age at testing ranged from 2.5 to 10.3 years. Adaptive Behavior Score (11 subjects), mean 93.5; estimated Intelligence Quotient/Developmental Quotient mean 93.5; Motor: mean 92.8. Residual opsoclonus myoclonus syndrome symptoms at the time of the evaluation were generally minor; opsoclonus myoclonus syndrome scores ranged from 0 to 6. Comparison to previously reported opsoclonus myoclonus syndrome subjects showed improved outcomes: Adaptive behavior, cognitive and motor scores were significantly higher (P < .001) in new subjects. Outcomes have improved with more aggressive immunosuppression, with most opsoclonus myoclonus syndrome survivors now functioning at or near normal.

The “neuro” of neuroblastoma: Neuroblastoma as a neurodevelopmental disorder

“…47 Although there are no randomized, controlled trials in OMAS, there are reasonable cohort studies (retrospective and prospective) to show that for patients with severe disease, multimodal therapy (adrenocorticotrophic hormone or corticosteroids plus rituximab, cyclophosphamide, or steroid sparing immune suppression) do better than patients given corticosteroids and intravenous immunoglobulin alone. 62,63 More-modern aggressive immune suppression appears to convey better outcomes in cognition and motor scores compared to historical treatments, 63 and early treatment with rituximab appears to improve outcomes compared to later treatment 64 ; however, it should be emphasized that none of these studies were randomized or controlled.…”

Management of Immune-Mediated Paraneoplastic Neurological Disorders

“…The outcomes achieved with the standard treatments (tumor therapy, corticosteroids or ACTH in pediatric patients, often combined with IVIG; if required, plasma exchange) are often unsatisfactory and associated with residual deficits [73]. More aggressive therapeutic strategies, such as rituximab and cyclophosphamide, can improve long-term prognosis, including cognitive and behavioral deficits [74,75].…”

Sensory Processing Difficulties in Opsoclonus-Myoclonus Syndrome

“…[3][4][5][6] A recent report suggests some improvements in outcomes with increased immunosuppression. 7 A neuroblastoma is present in about 50% of children and presumed to be an immune-mediated paraneoplastic condition whereby immune perturbations have been identified in the form of reactivity of patient derived humoral and cellular components to tumor cell lines. 8 Central nervous system autoreactivity in opsoclonus-myoclonus syndrome may also occur in the absence of tumor, where a postinfectious etiology is purported to be the trigger.…”