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NORD is very grateful to Michael R. Pranzatelli, MD, Professor of Neurology and Pediatrics, Founder & Director, National Pediatric Myoclonus Center; Department of Neurology, Southern Illinois University School of Medicine, for assistance in the preparation of this report
Opsoclonus-myoclonus syndrome (OMS) is a paraneoplastic neurological disorder. It is characterized by associated ocular, motor, behavioral, sleep, and language disturbances. The onset is usually abrupt, often severe, and can become chronic.
The component features of OMS include repeated, rapid eye movements in both horizontal and vertical directions (opsoclonus); unsteady, gait (ataxia); brief, repeated, shock-like spasms of several muscles within the arms, legs (myoclonus). Extreme irritability, reduced and fragmented sleep, rage attacks, difficulty articulating speech (dysarthria), or inability to speak (mutism), and decreased muscle tone (hypotonia) are common.
When opsoclonus and myoclonus occur together, the cause is a tumor until proven otherwise. In approximately 50 percent of affected individuals, a tumor of embryonic nerve cells (neuroblastoma) is responsible for the symptoms associated with OMS. In other cases, the disorder has been attributed to a viral infection such as Coxsackie virus B3, or St. Louis encephalitis virus, however, the high rate of spontaneous tumor regression means that the tumor may be gone before it is looked for. Other causes are even rarer.
OMS is a rare disorder: 1 in a million individuals worldwide. It usually affects infants and young children, although it is also known to affect adults. The peak age in children is about 18 months, with a long tail out to about 5 – 6 years. Occurrence in infants under 6 months is very quite uncommon, and opsoclonus in that age group, when isolated, is usually from another cause. It occurs in males and females in fairly equal numbers. OMS occurs in about 3% of all children with neuroblastomas.
Symptoms of the following disorders can be similar to those of OMS. Comparisons may be useful for a differential diagnosis:
About 95% of children with OMS are misdiagnosed as acute cerebellar ataxia because the ataxia may appear before the eye findings. This diagnosis causes delay in recognition and treatment of OMS. Once opsoclonus is present, however, the diagnosis cannot be acute cerebellar ataxia. Also, children with disproportional small amounts of opsoclonus or myoclonus are harder to recognize and may carry the wrong diagnosis for years. (For more information on this disorder, choose "Ataxia" as your search term in the Rare Disease Database.)
Myoclonus can occur in other contexts without opsoclonus and with or without ataxia. It may be epileptic or non-epileptic, rhythmical or arrhythmic, generalized or localized. Myoclonus may accompany a number of neurologic diseases, including seizure disorders, brain injuries, hereditary brain disorders, viral infections, and metabolic or toxic disorders. In arrhythmic myoclonus, the more common type, muscle jerks are irregular and unpredictable. (For more information on this disorder, choose "Myoclonus" as your search term in the Rare Disease Database.)
The diagnosis of opsoclonus-myoclonus is clinical; there is not diagnostic test yet, as the antigen remains unidentified. The presence of the "dancing eyes," the shock-like muscle spasms, and the stumbling gait, especially if accompanied by irritability, are highly reliable indicators of this syndrome. To detect a tumor, both a CT scan of the neck, chest, abdomen, and pelvis (with oral and IV contrast), as well as an MIBG scan need to be done. In addition, special immunologic studies may be undertaken to determine the presence of abnormal white blood cells in the spinal fluid that are not detectable by routine studies, using a technique called immunophenotyping. Autoantibodies found in OMS may be detectable at research but not commercial laboratories.
The main tenet of treatment for OMS is early and sufficient immunotherapy with the goal of putting them into a durable complete neurological remission. If a tumor is present, surgery is typically required. The tumors are usually low stage (I or II) and tumor chemotherapy or radiation therapy are not indicated. Tumor resection does not usually provide sufficient clinical benefit for OMS, however. OMS treatment, which is usually continued over 1-2 years, should involve combined immunotherapies as soon as possible after diagnosis.
FLAIR therapy is a three-agent protocol involving front-loaded high-dose ACTH, IVIg, and rituximab that was developed by the National Pediatric Myoclonus Center, and has the best-documented outcomes. Almost all patients (80-90%) show improvement with this treatment. Over time, treatment with ACTH may have mostly cortisol-related adverse effects that must be monitored carefully. Pulse dose dexamethasone instead of ACTH is an option in milder cases. The use of prednisone-type oral steroids is not recommended, because they are the least effective of the steroids for OMS. Rituximab is a monoclonal antibody against B cells (anti-CD20). For OMS relapse, low-dose cyclophosphamide (3-6 cycles) or more rituximab (1-2 cycles) are given.
Almost all children with neuroblastoma and OMS survive their tumor, which usually does not behave aggressively, though some tumors may be large in size and pose difficulties for resection. In contrast, OMS is the main issue, and the OMS relapse rate in cases treated with only conventional agents is 50-75%. With FLAIR therapy, the relapse rate appears to be about 20%. OMS onset in the first year of life is particularly damaging to expressive speech and language development, and may result in a higher incidence of cognitive impairment. The best responders appear to be those who received early combination therapy and were only of mild to moderate severity. Failure to achieve complete neurological remission and multiple relapses (chronic-relapsing OMS) usually results in permanent deficits, such as ADD/ADHD, OCD, and cognitive impairment. Children in the chronic sick role can become oppositional, depressed, and aggressive.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll free: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
Contact for additional information about opsoclonus-myoclonus syndrome:
Dr. Michael R. Pranzatelli
Director, National Pediatric Myoclonus Center
P.O. Box 19643
Springfield, IL 62794-9643
Pranzatelli MR, Tate ED. Opsoclonus-myoclonus syndrome. In: Russell CD, Vincent A, eds. Clinics in Developmental Medicine No. 184-185, Inflammatory and Autoimmune Disorders of the Nervous System in Children. London, UK: Mac Keith Press; 2010;152-173.
Pranzatelli MR. Opsoclonus-Myoclonus Syndrome. In: NORD Guide to Rare Disorders. Philadelphia, PA: Lippincott Williams & Wilkins; 2003:572-73.
Tate ED, Pranzatelli MR, Verhulst SJ, et al. Active comparator-controlled, rater-blinded study of ACTH-based immunotherapies for OMS. Journal of Child Neurology. 2012;27(7):875-84.
Pranzatelli MR, Tate ED, McGee NR, et al. Key role of CXCL13/CXCR5 axis for cerebrospinal fluid B cell recruitment in pediatric OMS. J Neuroimmunol. 2012;243(1-2):81-8.
Pranzatelli MR, Tate ED, Travelstead AL, Verhulst SJ. Chemokine/cytokine profiling after rituximab: reciprocal expression of BCA-1/CXCL13 and BAFF in childhood OMS. Cytokine. 2011;53:384-389.
Pranzatelli MR, Slev PR, Tate ED, Travelstead AL, Colliver JA, Joseph SA. Cerebrospinal fluid oligoclonal bands in childhood opsoclonus-myoclonus. Pediatric Neurology. 2011;45(1):27-33.
Pranzatelli MR, Tate ED, Swan JA, et al. B cell depletion therapy for new-onset opsoclonus-myoclonus. Movement Disorders. 2010;25(2):238-242.
Pranzatelli MR, Tate ED, Verhulst SJ, et al. Pediatric dosing of rituximab: serum concentrations in opsoclonus-myoclonus syndrome. Journal of Pediatric Hematology and Oncology. 2010;32(5):e167-e172.
Pranzatelli MR, Tate ED, Hoefgen ER, et al. Therapeutic down-regulation of central and peripheral B-cell-activity-factor (BAFF) production in pediatric opsoclonus-myoclonus syndrome. Cytokine. 2008;44:26-32.
Blaes F, Pike MG, Lang B. Autoantibodies in childhood opsoclonus-myoclonus syndrome. J Neuroimmunol. 2008;201-202:221-6.
Pranzatelli MR, Tate ED, Travelstead AL, et al. Rituximab (anti-CD20) adjunctive therapy for opsoclonus-myoclonus syndrome. J Pediatr Hematol Oncol. 2006;28;585-593.
Tate ED, Allison TJ, Pranzatelli MR, et al. Neuroepidemiologic trends in 105 US cases of pediatric opsoclonus-myoclonus syndrome. J Pediatr Oncol Nurs. 2005;22:8-19.
Mitchell WG, Brumm VL, Azen CG, et al. Longitudinal neurodevelopmental evaluation of children with opsoclonus-ataxia. Pediatrics. 2005;116:901-907.
Pranzatelli MR, Travelstead AL, Tate ED, et al. B- and T-cell markers in opsoclonus-myoclonus syndrome: immunophenotyping of CSF lymphocytes. Neurology. 2004;62:1526-32.
Bataller L, Rosenfeld MR, Graus F, et al. Autoantigen diversity in the opsoclonus myoclonus syndrome. Ann Neurol. 2003;53:347-53.
Swart JF, de Kraker J, van der Lely N. Metaiodobenzylguanidine total-body scintigraphy required for revealing occult neuroblastoma in opsoclonus-myoclonus syndrome. Eur J Pediatr. 2002;161:255-58.
Pranzatelli MR, Tate ED, Wheeler A, et al. Screening for autoantibodies in children with opsoclonus myoclonus ataxia. Pediatr Neurol. 2002;27:384-87.
Blaes F. Immunotherapeutic approaches to paraneoplastic neurological disorders. Expert Opin Biol Ther. 2002;2:419-30.
Pranzatelli MR, Tate ED, Kinsbourne M, et al. Forty-one year follow-up of childhood-onset opsoclonus myoclonus ataxia, cerebellar atrophy, multiphasic relapses, and response to IVIG. Mov Disord. 2002;17:1387-90.
Hayward K, Jeremy RJ, Jenkins S, et al. Long-term neurobehavioral outcomes in children with neuroblastoma and opsoclonus myoclonus ataxia syndrome: relationship to MRI findings and anti-neuronal antibodies. J Pediatr. 2001;139:552-59.
NINDS Opsoclonus Myoclonus Information Page. NINDS/NIH. http://www.ninds.nih.gov/disorders/opsoclonus_myoclonus/opsoclonus_myoclonus.htm. Last updated February 14, 2007. Accessed July 19, 2012.
Report last updated: 2012/07/30 00:00:00 GMT+0