Opsoclonus-Myoclonus Ataxia Syndrome

Opsoclonus myoclonus syndrome is a rare disorder of the nervous system. It is characterized by associated ocular, motor, behavioral, sleep, and language disturbances. The onset of the disorder is usually abrupt, often severe, and can become chronic

Introduction

  • Opsoclonus myoclonus syndrome is a rare disorder of the nervous system. [1,2]
  • It is characterized by associated ocular, motor, behavioral, sleep, and language disturbances.
  • The onset of the disorder is usually abrupt, often severe, and can become chronic. [3]

Epidemiology

  • Usually affects infants and young children but has been identified in adults.
  • The peak age of incidence is between 6 and 36 months of age with the acute or subacute disease.
  • More prevalent in boys than girls.
  • In adults, Paraneoplastic cases usually present in their 60s while Idiopathic cases tend to present in their 30s or 40s.

Pathophysiology

  • Although the pathophysiology is unclear, it is believed to be immunologically based on the association between paraneoplastic tumors. [1,6,7]
  • Tissue dysfunction is often attributed to both humoral and cellular immune attacks.
  • There is a cellular immune reaction against onconeural antigens leading to the disinhibition of the Fastigial nucleus-Purkinje cell network of the cerebellum.
  • A number of autoantibodies have been identified to a variety of antigens and cerebrospinal fluid B-cells are found to be increased.
  • These antibodies include Glycine receptor, Hu (ANNA-1), Ri (ANNA-2), Glutamate receptor, Neurofilament, Yo, Ma1, Ma2, Amphiphysin, CRMP-5/anti-CV2, and Zic. [7]
  • The majority of patients do not have these antibodies in their blood or CSF, so they are less diagnostic.

Clinical Features

  • Opsoclonus; a condition characterized by excessive eye movement, sometimes referred to as "dancing eyes". This condition is marked by rapid, repetitive conjugate eye movements that are involuntary, arrhythmic, chaotic, and multidirectional (horizontal, vertical, and torsional components) with no saccadic intervals. [1,6]
  • Myoclonus; a clinical sign that involves brief, shock-like, involuntary movements due to muscular contractions or inhibitions. [6]
  • Ataxia; characterized by the inability to sit or stand due to a lack of control of muscles or voluntary movements by the patient. [6]
  • Behavioral changes include irritability and sleep disturbances. [6]
  • Speech difficulties; slurred speech, inability to speak, and difficulty understanding speech.
  • Decreased muscle tone
  • Nausea and/or vomiting

Associations

The syndrome is associated with the following conditions: [1,2,3]

Paraneoplastic

Neural crest tumors

  • Neuroblastoma
  • Ganglioneuroblastoma
  • Ganglioneuroma
  • Small cell carcinoma of the lung

Non-neural crest tumors

  • Breast carcinoma
  • Renal cell carcinoma
  • Malignant fibrous histiocytoma
  • Pancreatic carcinoma
  • Malignant melanoma

Para-infectious

  • HIV
  • Epstein Barr Virus
  • Coxsackie B3
  • Mumps
  • Mycoplasma Pneumoniae

Miscellaneous

  • Hyperosmolar coma
  • Celiac disease
  • Following hematopoietic stem cell transplantation

Diagnosis and Evaluation

💡
The diagnosis is clinical; there is no diagnostic test yet, as the antigen remains unidentified.

Investigations in a child with the opsoclonus–myoclonus symptoms to rule out occult neuroblastoma [1,4]

  • Detailed history and neurological examination
  • Contrast-enhanced CT scan of the chest, abdomen, and pelvis
  • Iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy
  • 24-hour urinary catecholamines quantitative assessment (Homovanillic acid and Vanillylmandelic acid)
  • Biopsy of tumor and immunohistochemistry, if indicated

Treatment

The goal of the treatment of OMAS is to decrease the symptoms. [1,6,7]
  • Patients with related neuroblastoma are treated with tumor resection.
  • OMAS treatment, which is usually continued over at least 1-2 years, should involve combined immunotherapies as soon as possible after diagnosis.
💡
A three-agent protocol involving initial use of high-dose ACTH (corticotropin), IVIG, and rituximab has the best-documented outcomes for moderately severe and severe cases.
  • Patients without tumors are treated with the following:
  1. ACTH and Oral corticosteroids
  1. Plasmapheresis
  1. Intravenous Immunoglobulin
  1. Rituximab

Treatment for OMAS Relapse

  • Low-dose IV cyclophosphamide (3-6 cycles) or repeated courses of rituximab (1-2 cycles) are given.
  • Oral weekly methotrexate may be a useful steroid sparer in chronic relapse.

Prognosis

  • We know little about the prognosis for lack of prospectively defined cohort studies with systematically controlled clinical data.
  • Another problem is a small sample size and research as it is a rare disease. [5]
  • According to the data available, all children with neuroblastoma and OMS survive their tumor, which usually does not behave aggressively, though some tumors may be large and pose difficulties for resection.
  • The prognosis in adults with paraneoplastic OMS is poor as compared to idiopathic opsoclonus myoclonus despite treatment with corticosteroids or IVIG.

Further Reading

  • Saini, L., Dhawan, S. R., Madaan, P., Suthar, R., Saini, A. G., Sahu, J. K., & Sankhyan, N. (2020). Infection-associated opsoclonus: a retrospective case record analysis and review of literature. Journal of child neurology, 35(7), 480-484.
  • Klaas, J. P., Ahlskog, J. E., Pittock, S. J., Matsumoto, J. Y., Aksamit, A. J., Bartleson, J. D., ... & McKeon, A. (2012). Adult-onset opsoclonus-myoclonus syndrome. Archives of neurology, 69(12), 1598-1607.

Bibliography

  • Sahu, J. K., & Prasad, K. (2011). The opsoclonus–myoclonus syndrome. Practical neurology, 11(3), 160-166.
  • Oh, S. Y., Kim, J. S., & Dieterich, M. (2019). Update on opsoclonus–myoclonus syndrome in adults. Journal of neurology, 266(6), 1541-1548.
  • Pike, M. (2013). Opsoclonus–myoclonus syndrome. Handbook of clinical neurology, 112, 1209-1211.
  • Kim, D. D., & Budhram, A. (2018). Opsoclonus-Myoclonus Syndrome—Additional Clinical Considerations. JAMA Otolaryngology–Head & Neck Surgery, 144(4), 387-388.
  • Opsoclonus-Myoclonus Syndrome - NORD (National Organization for Rare Disorders). (2019, July 24). NORD (National Organization for Rare Disorders); NORD. https://rarediseases.org/rare-diseases/opsoclonus-myoclonus-syndrome/
  • UpToDate. (2022). Uptodate.com. https://www.uptodate.com/contents/opsoclonus-myoclonus-syndrome
  • Lino, A. M. M., Spera, R. R., de Campos, F. P. F., de Andrade Freitas, C. H., Garcia, M. R. T., da Costa Lopes, L., & Prokopowitsch, A. S. (2014). Adult-onset opsoclonus-myoclonus-ataxia syndrome as a manifestation of brazilian lyme disease-like syndrome: a case report and review of literature. Autopsy & case reports, 4(1), 29.