Neuroepidemiologic Trends in 105 US Cases of Pediatric Opsoclonus-Myoclonus Syndrome

Abstract

Opsoclonus-myoclonus syndrome (OMS) is a rare, autoimmune neurological disorder that is poorly recognized and undertreated. Neuroblastoma is found in one half of the cases. Because of the high incidence of spontaneous regression of neuroblastoma, it is unknown whether not finding a tumor means there was none. To define demographic trends and the standard of care in the first large series of OMS, 105 children were recruited over a 13-year period in a retrospective questionnaire survey. Children with and without a tumor differed little in viral-like prodrome and neurological symptoms. Earliest neurological symptoms were staggering and falling, leading to a misdiagnosis of acute cerebellitis. Later symptoms included body jerks, drooling, refusal to walk or sit, speech problems, decreased muscle tone, opsoclonus, and inability to sleep. Tumor resection alone did not provide adequate therapy for most. Adrenocorticotropic hormone (ACTH), prednisone, and intravenous immunoglobulin were used with equal frequency, but ACTH was associated with the best early response. More than one half of the children had relapses. Residual behavioral, language, and cognitive problems occurred in the majority. The delay in diagnosis (11 weeks) and initiation of treatment (17 weeks) is unacceptably long.

Paraneoplastic neurologic disorders

“…Neuroblastoma is accompanied by 40% in case of pediatric opsoclonus-myoclonus. In this case, findings such as hypotonia, mental retardation may be observed (Rudnick et al, 2001;Tate et al, 2005). The brain MRI is usually normal.…”

Opsoclonus Myoclonus Ataxia Syndrome

“…OMA is most commonly associated with neural crest derived tumours, (like neuroblastoma (up to 40%), ganglioneuroblastoma, ganglioneuroma), as a para-neoplas c presenta on 3 . The pathogenesis was thought to be immune mediated, with a cross-reac ve autoimmunity between neuroblastoma cells and the central nervous system 4 .…”

“…This condi on is one of the important diff eren als for acute post infec ous cerebellar ataxia and is mainly dis nguished by presence of irritability and opsoclonus in OMA, which are rare in the former. In contrast to cerebellar ataxia, the outcome is far disabling and requires more extensive work up as well as long term immunomodula on therapy 3 .…”

Genetic features of neuroblastic tumors associated with opsoclonus-myoclonus syndrome opens up the possibility for detection in peripheral blood

“…OMS is characterized by involuntary, omnidirectional eye movements (which may continue during sleep), and/or by myoclonus and ataxia of the limbs ('dancing feet'), the trunk, and the eyelids [1,2]. A pathogenic role of the surface-binding autoantibodies against cerebellum and brainstem by cross-reactivity between onconeural antigens is suspected, although specific immunologic and genetic mechanisms are unclear [3][4][5][6][7][8][9].…”