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

• Myoclonus
• Leigh's Disease
• Kernicterus

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.

Other symptoms that are usually less frequently encountered or less pronounced are difficulty in speaking (dysphasia), difficulty articulating speech (dysarthria), inability to speak (mutism), decreased muscle tone (hypotonia), lethargy, irritability, and a vague feeling of bodily discomfort (malaise).

When opsoclonus and myoclonus occur together, the cause is usually either a tumor or a viral infection. Other causes are even more rare.

In about half of the cases, the cause is a tumor, either a neuroblastoma or a ganglioneuroblastoma. These are tumors of embryonic nerve cells that are often found in the chest, pelvis or abdomen. Note that these tumors involve the same primitive cells that develop into brain cells. Because such tumors are located so far from the appropriate organ (in this case the brain), they are known as "paraneoplastic", and OMS is sometimes called a paraneoplastic disorder.

In most other cases, opsoclonus myoclonus is due to a viral infection such as Coxsackievirus B3, poliovirus, or St. Louis encephalitis virus. In the process of diagnosis, experts warn that the presence of a virus must be confirmed and, even then, the presence of a tumor must also be considered.

In rare cases, the disorder may result due to other underlying causes such as a tumor within the skull (intracranial tumors) or hydrocephalus, a condition in which inhibition of the normal flow of cerebrospinal fluid (CSF) and abnormal widening (dilatation) of the cerebral spaces of the brain (ventricles) causes accumulation of CSF in the skull and potentially increased pressure on brain tissue.

How a tumor located far from the brain, or a viral infection, can cause a malfunction of the brain like OMS is a question that remains to be answered.

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:

Myoclonus is a group of movement disorders characterized by sudden, involuntary contractions of a skeletal muscle or group of muscles. It may be divided into two groups, rhythmical and arrhythmic myoclonus. Myoclonus may accompany a number of neurologic diseases, including seizure disorders, brain injuries, hereditary brain disorders, viral infections, and neuroblastomas. 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.)

Rhythmical, or segmental, myoclonus is characterized by synchronized muscle jerks with a constant frequency of between ten and one hundred and eighty jerks per minute. (For more information on this disorder, choose "Myoclonus" as your search term in the Rare Disease Database.)

Leigh's disease is a genetic metabolic disorder characterized by lesions of the brain, spinal cord, optic nerve and in some cases, an enlarged heart. The disorder is usually first diagnosed during infancy but may begin later. Symptoms during infancy may include low body weight, slow growth, tremors, skin changes and interrupted breathing patterns. Progressive neurological disturbances, mental retardation, slurred speech and loss of motor coordination (ataxia) may occur in cases beginning during or after infancy. Abnormalities of eye movement and other vision problems may develop in cases with later onset. (For more information on this disorder, choose "Leigh" as your search term in the Rare Disease Database.)

Kernicterus is a condition characterized by an excess of bilirubin in the blood during infancy. The bilirubin is deposited in the basal ganglia of the brain and in the brainstem nuclei. Early symptoms of kernicterus in full term infants may include lethargy, poor feeding and vomiting, a spasm with head and heels bent backward and the body bowed forward (opisthotonus), upward deviation of the eyes, convulsions and muscular rigidity. Later in childhood the patient may show ceaseless jerky movements and slow sinuous writhing movements (choreoathetosis), sensorineural hearing loss, and loss of upward gaze. (For more information on this disorder, choose "Kernicterus" as your search term in the Rare Disease Database.)

Diagnosis
The diagnosis of opsoclonus myoclonus is confirmed by a thorough clinical evaluation and a variety of specialized tests, detailed patient history, and special-ized laboratory tests.

The presence of the "dancing eyes", the shock-like muscle spasms, and the stumbling gait, especially if accompanied by involuntary tremors, are highly reliable indicators of this syndrome. Patients usually undergo a series of laboratory tests designed to determine the presence and concentration of various key antibodies. In addition, special immunologic studies may be undertaken to determine the presence of abnormal white blood cells.

When a neuroblastoma is suspected, thorough magnetic resonance imaging (MRI) studies are indicated.

Treatment
If a tumor is present, chemotherapy, surgery, or radiation may be required. The opsoclonus myoclonus symptoms may improve afterward. In adults, removal of the tumor may less frequently result in the easing of symptoms.

Treatment may involve corticosteroids or ACTH (adrenocorticotropic hormone). A protocol involving high-dose ACTH has been developed at the National Pediatric Myoclonus Center. Over time, treatment with ACTH may have substantial adverse effects that must be monitored carefully. Almost all patients (80-90%) show improvement with this treatment, but withdrawal of ACTH often brings back the original symptoms.

Another treatment option with fewer side effects is the administration of human intravenous immunoglobulins (IVIG). However, fewer patients respond favorably to IVIG treatment.

Basic and clinical research on opsoclonus myoclonus is active at the National Pediatric Myoclonus Center, under the direction of Dr. Michael R. Pranzatelli. For information, those interested in participating in these studies should ask their doctor to contact:

Michael R. Pranzatelli, M.D .
Professor, Departments of Neurology & Pediatrics
Director, National Pediatric Myoclonus Center
Southern Illinois University School of Medicine
P.O. Box 19658
Springfield, IL 62794-0702
Telephone: 217-785-0702
e-mail: oms@siumed.edu

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:

Tollfree: (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.

Fauci AS, Braunwald E, Isselbacher KJ, et al., eds. Harrison’s Principles of Internal Medicine. 14th ed.McGraw-Hill Companies. New York, NY; 1998:624-25.

Menkes JH, Pine Jr JW, et al., eds. Textbook of Child Neurology. 5th ed. Williams & Wilkins. Baltimore, MD; 1995:422, 427.

Rowland LP. Ed. Merritt’s Neurology. 10th ed. Lippincott Williams & Wilkins. Philadelphia, PA. 2000:667, 894.

REVIEW ARTICLES
Gatti G, Simsek S, Kurne A, et al. Paraneoplastic neurological disorders in breast cancer. Breast. 2003;12:203-07.

Musunuru K. Cell-specific RNA-binding proteins in human disease. Tends Cardiovasc Med. 2003;13:188-95.

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
Ramadan M, Whalen B, De Santes K. Hyperexcitable blink reflex preceding the diagnosis of neuroblastoma. J Pediatr Hematol Oncol. 2004;26:665-67.

Dale RC, Heyman I, Surtees RA, et al. Dyskinesias and associated psychiatric disorders following streptococcal infections. Arch Dis Child. 2004;89:604-10.

R SS, Mani PJ. Opsoclonus myoclonus syndrome: response to plamapheresis. Indian Pediatr. 2004;41:499-502.

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.

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, 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.

Danesh-Meyer HV. Ahhh, that’s a strange eye movement! Surv Ophthalmol. 2002;47:263-66.

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.

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.

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