Introduction: Opsoclonus-myoclonus syndrome (OMS) is a serious orphan disease in need of neuroepidemiological studies.

Methods: 24-year, IRB-approved, observational study at NPMC. N=357 U.S./32 other countries. Statistical analysis: medians (with IQR). Follow-up:1.9 y(1-3.4).

Results: Age: 2.7 y(1.9-4). Gender: 215 females/174 males(1.2:1). Race:85%-White, 10%-Black, 3%-Asian/Oceanic, 1%-Native American, 0.2%-Indian. Ethnicity:15%-Hispanic. OMS onset age: 1.5y(1.2-2). Time to diagnosis:1.2 mo(0.7-3). At initial evaluation, 25%-acute, 32%-subacute, 43%-chronic; 18%-untreated, 22%-only-previously-treated, 60%-on-treatment (25%-monotherapy/14%-multimodal). Severity scores (OMES):39%-mild, 34%-moderate, 17%-severe. Tumor frequency was 50%:58%-abdominal/26%-thoracic/6%-pelvic/2%-cervical. Tumor type:73%-neuroblastoma/22%-ganglioneuroblastoma/5%-ganglioneuroma. Neuroblastoma INNS stage:58%-I/35%-II/5%-III/2%-IV. Neuroblastoma:commonest type in young (p = .004), more Stage I (p = .002). Patients with tumor not distinguishable by prodromal symptoms, onset age, OMS severity, relapse rate, rank order of OMS sign appearance, or geographic distribution. OMS was non-relapsing (monophasic) in 59%, relapsing-remitting in 36%, relapsing-progressive in 5%. 53% of relapsers had 1 relapse, 20%-2, 27%-3-or-more (annualized rate 0.1/y). First relapse trigger (48%-treatment-taper/40%-infection/12%-both/other) predictive of subsequent ones. A single relapse carried a 47% risk of another/2 relapses-57%/3 relapses-35%. OMS duration at first relapse was 1.5 y(0.7-2.5); at last relapse 2.3 y(1.4-4). Chronic relapsers could not be predicted initially on clinical grounds. Of the 7% of OMS that never attained remission (Total-Score ≤ 6), 73% had cognitive impairment;73% had relapsed at least once.

Conclusions: In this largest reported series, OMS has a propensity for relapse. Failure to remit and relapses were the main associations with cognitive impairment. A different approach to OMS based on the tumor vs idiopathic dichotomy was not supported. Biomarkers for relapse prediction and better prevention measures are needed.