Information on the following diseases can be found in the Related Disorders section of this report:

• Myoclonus
• Cerebellar Ataxia

Opsoclonus-myoclonus syndrome is characterized by 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) and interrupted, rhythmic and involuntary motion during a voluntary movement of an arm or leg. Irritability, reduced 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 opsoclonus-myoclonus. In other cases, the disorder may be due to a viral infection such as Coxsackievirus B3, poliovirus, 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 more rare.

Opsoclonus-myoclonus syndrome is a rare disorder that usually affects infants and young children, although it is also known to affect adults. It is found in males and females in equal numbers.

Symptoms of the following disorders can be similar to those of opsoclonus myoclonus. Comparisons may be useful for a differential diagnosis:

Most children with opsoclonus-myoclonus are misdiagnosed as acute cerebellar ataxia because the ataxia may appear before the eye findings. Once opsoclonus is present, however, the diagnosis cannot be acute cerebellar ataxia. (For more information on this disorder, choose "Ataxia" as your search term in the Rare Disease Database.)

Myoclonus is a group of movement disorders characterized by sudden, involuntary contractions of a skeletal muscle or group of muscles. 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. Single muscles, or the entire skeletal musculature may be affected. (For more information on this disorder, choose "Myoclonus" as your search term in the Rare Disease Database.)

Diagnosis
The diagnosis of opsoclonus-myoclonus is clinical. 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, 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. This technique, called immunophenotyping, reveals increased B cells. Autoantibodies found in opsoclonus-myoclonus are detectable at research but not commercial laboratories.

Treatment
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 opsoclonus-myoclonus syndrome.

Treatment should involve combined immunotherapies as soon as possible after diagnosis. A protocol involving high-dose ACTH, IVIg, and rituximab has been developed at the National Pediatric Myoclonus Center. Almost all patients (80-90%) show improvement with this treatment. Over time, treatment with ACTH may have substantial adverse effects that must be monitored carefully. Pulse dose dexamethasone or corticosteroids instead of ACTH are options in milder cases. Rituximab is a monoclonal antibody against B cells(anti-CD20). The use of low-dose cyclophosphamide is also under evaluation.

Prognosis
The best responders appear to be those who got early combination therapy and were only of mild to moderate severity. Failure to achieve complete neurological remission and multiple relapses usually results in permanent deficits, such as ADD/ADHD and cognitive impairment.

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
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

TEXTBOOKS
Pranzatelli MR. Opsoclonus-Myoclonus Syndrome. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:572-73.

REVIEW ARTICLES
Blaes F. Immunotherapeutic approaches to paraneoplastic neurological disorders. Expert Opin Biol Ther. 2002;2:419-30.

Pranzatelli MR. Paraneoplastic syndromes: An unsolved murder. Semin Pediatr Neurol. 2000.7:118-130.

JOURNAL ARTICLES
Bataller L, Rosenfeld MR, Graus F, et al. Autoantigen diversity in the opsoclonus myoclonus syndrome. Ann Neurol. 2003;53:347-53.

Blaes F, Pike MG, Lang B. Autoantibodies in childhood opsoclonus-myoclonus syndrome. Neuroimmunol. 2008; Aug 5 [Epub ahead of print].

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.

Mitchell WG, Brumm VL, Azen CG, et al. Longitudinal neurodevelopmental evaluation of children with opsoclonus-ataxia. Pediatrics. 2005;116:901-907.

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.

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.

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.

Pranzatelli MR, Tate ED, Wheeler A, et al. Screening for autoantibodies in children with opsoclonus myoclonus ataxia. Pediatr Neurol. 2002;27:384-87.

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.

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.

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.

FROM THE INTERNET
NINDS Opsoclonus Myoclonus Information Page. NINDS/NIH. Reviewed 7/29/2004.
www.ninds.nih.gov/health_and_medical/disorders/opsomyo_doc.htm

What is the Opsoclonus-Myoclonus Syndrome? nd. 6pp
www.omsusa.org/pranzatelli-Brochure1.htm