Neuroblastoma-associated opsoclonus-myoclonus-ataxia syndrome: an important yet overlooked diagnosis in pediatric ataxia

Abstract

Background. Opsoclonus-myoclonus-ataxia syndrome (OMAS) is a rare, immune-mediated neurological disorder, often associated with neuroblastoma (NB) in children. This study aimed to describe the clinical features, diagnostic challenges, treatment, and outcomes of pediatric patients with NB-associated OMAS. Methods. We retrospectively reviewed medical records of seven children diagnosed with NB-associated OMAS between November 1, 2015 and January 31, 2025. Data on demographics, clinical presentation, tumor characteristics, treatment protocols, relapses, and outcomes were collected. The Mitchell-Pike OMS Rating Scale was used to assess severity. Results. The cohort included four girls and three boys, aged 18-36 months (median 31). All had a history of infection and/or vaccination preceding symptom onset. Ataxia was the most common initial symptom (6/7, 85.7%), followed by behavioral disturbances and sleep disorders (5/7, 71.4% each). At presentation, opsoclonus was present in two patients, which was initially misdiagnosed as nystagmus. All but one patient had opsoclonus during the disease course. Neuroblastomas were located in abdominal (n=4), thoracic (n=1), and sacral (n=2) regionsall tumors measured <50 mm and were stage L1. First-line treatment included tumor resection, intravenous immunoglobulin, and corticosteroids. Three patients required second-line therapy (rituximab, cyclophosphamide, mycophenolate mofetil, or azathioprine). After a median follow-up of 40 months (range 26-64), four patients had no neurological sequelaethree had mild cognitive impairment. Conclusion. NB-associated OMAS may present with non-specific symptoms, leading to diagnostic delays. Early recognition, thorough tumor screening, and prompt immunotherapy may improve neurological outcomes. Clinicians should suspect NB in children presenting with ataxia and behavioral/sleep disturbances, even in the absence of opsoclonus or abnormal findings on initial imaging.