Opsoclonus-Myoclonus Syndrome

Opsoclonus myoclonus syndrome (OMS) is a rare neuroinflammatory disease of paraneoplastic, parainfectious or idiopathic origin, characterized by opsoclonus, myoclonus, ataxia, and behavioral and sleep disorders.

Epidemiology

The annual incidence is estimated at around 1/5,000,000.

Clinical description

OMS typically presents between 1 and 3 years of age, although it can occur earlier or later in childhood. It is characterized by opsoclonus (rapid, multi-directional, conjugate eye movements), myoclonic jerks, ataxia, irritability and sleep disturbances. The clinical course may be monophasic or chronic relapsing. OMS is associated in approximately 50% of pediatric cases with a neuroblastoma (see this term); this tumour is usually (but not always) of low grade with a good oncological outcome. A similar adult-onset condition also occurs but is associated with different types of cancer, most commonly small-cell lung cancer (see this term) and adenocarcinoma of the breast.

Etiology

OMS may have a paraneoplastic, parainfectious or idiopathic origin. In the majority of pediatric paraneoplastic cases, a neuroblastoma is found. Infections triggering OMS include a variety of viral and bacterial agents including streptococci, mycoplasma and varicella zoster. The exact pathomechanism is unknown but an autoimmune-mediated brainstem and/or cerebellar dysfunction has been suggested; the opsoclonus may reflect disinhibition of the fastigial nucleus of the cerebellum or disordered interaction between the omnipause and burst neurons, but the cognitive and behavioral elements of the condition, as well as recent imaging studies, suggest a wider neurological process.

Diagnostic methods

The diagnosis is clinical, based on the presence of 3 out of the 4 following criteria: 1) neuroblastoma, 2) opsoclonus, 3) a movement disorder with myoclonus and/or ataxia, and 4) behavioural and/or sleep disturbance. Brain MRI in the acute presentation is normal. Neuroblastoma is detected by detailed MRI with particular focus on the whole length para-spinal regions, the carotids, the mediastinum, the adrenals, the abdomen and pelvis. Functional tests, including urinary vanillylmandelic and homovanillic acid tests and a metaiodobenzylguanidine scan, should be performed but may produce a false negative result as neuroblastomas in OMS are usually low grade and therefore not metabolically active. Serological tests may allow for the identification of a parainfectious etiology. No consistent neural antibody has yet been identified in pediatric OMS, in contrast to adult OMS in which Hu anti-neuronal nuclear antibodies (anti-Hu) have been found.

Differential diagnosis

Differential diagnosis includes acute inflammatory cerebellar ataxia that is differentiated from OMS by the type of eye movement (nystagmus), the absence of irritability, and the usually rapid recovery without treatment.

Management and treatment

Treatment usually includes resection of the neuroblastoma if present; occasionally, higher grade neuroblastoma may require chemotherapy. Treatment also includes immunomodulation. Treatment regimens have not been standardized but may include corticosteroids, adrenocorticotropin hormone, cyclophosphamide, intravenous immunoglobulin, and/or rituximab.

Prognosis

Outcome is variable. Some children have a monophasic illness, respond well to steroids and have little or no sequelae. Others may be treatment-resistant, have a chronic relapsing course and motor, cognitive and/or behavioral sequelae. Opsoclonus usually remits. The presence or absence of neuroblastoma does not seem to affect outcome.