Opsoclonus-Myoclonus Syndrome (OMS): Causes, Symptoms, Diagnosis and Treatement

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A little kid with Opsoclonus-Myoclonus Syndrome

1Overview

Opsoclonus-Myoclonus syndrome (OMS), also called dancing eyes-dancing feet syndrome, Kinsbourne syndrome, or Kinsbourne syndrome is a rare inflammatory neurological disease of parainfectious, idiopathic, or paraneoplastic origin. It is a result of an autoimmune process that involves the nervous system. It is defined by associated behavioral, motor, ocular, language, and sleep disturbances. The outbreak is often severe and usually abrupt, and it has the possibility to become chronic. The clinical course may be monophonic or chronic relapsing. OMS normally occurs in association with neuroblastoma or tumors or following a bacterial or viral infection. This tumor is normally of low grade with a good oncological outcome. There is a similar adult-onset disorder that could occur but it is associated with various kinds of cancers, frequently adenocarcinoma of the breast and small-cell lung cancer.

OMS is an extremely rare disease which affects 1 in 10,000,000 people. It normally affects infants and young children but it can also affect adults. It usually occurs between 1 and 3 years of age and peaks when a child is 18 months old but could extend up to the age of 5 or 6. There are instances of occurrence of this disease when an infant is just 6 months old. It can occur earlier or later in childhood. This disease is common in children with neuroblastomas which affects about 3% of them and this disease has been observed to occur with diseases of autonomic and neurologic dysfunction and also celiac disease.

2Causes

OMS can be of parainfectious, idiopathic, or paraneoplastic origin. A neuroblastoma is found in most of the pediatric paraneoplastic cases of OMS. Infections that trigger OMS include different bacterial and viral agents such as varicella zoster, mycoplasma, and streptococci. The exact pathomechanism is not known but it has been suggested that it may be because of a cerebellar dysfunction and/or an autoimmune-mediated brainstem. The opsoclonus may reflect the disordered interaction between burst neurons and the omnipause or the disinhibition of the fastigial nucleus of the cerebellum. The behavioral and cognitive elements of the disease suggest a wider neurological process.

When myoclonus and opsoclonus occur together, it usually results from a tumor unless ruled out by the doctor. The tumor is an occult body cavity tumor. In most cases of children who are affected with OMS, a tumor that starts in nerve cells found in an embryo, also known as neuroblastoma, may be accountable for the symptoms brought about by OMS.

In other cases, OMS may be idiopathic in nature which may be attributed to different bacterial and viral infections such as St. Louis encephalitis virus, Coxsackievirus B3, Epstein-Barr, enterovirus, or the simple flu. The tumor can be long gone before it is even detected with the high rate of spontaneous tumor regression. Lyme disease is also believed to cause OMS.

In adults, cases for OMS are associated with small-cell lung carcinoma or breast carcinoma. OMS is one of the syndromes indirectly caused by cancer (paraneoplastic) which may occur in children and adults, although the method of immune dysfunction underlying the adult OMS is quite different.

OMS is not considered as an infectious disease. It is also not considered a hereditary disease.

3Symptoms

Signs and symptoms of Opsoclonus-Myoclonus syndrome may include:

  • random, repeated, and rapid eye movements in both vertical and horizontal directions (opsoclonus)
  • Unsteady and trembling gait (ataxia)
  • Decreased muscle tone (hypotonia)
  • Inability to speak (mutism)
  • Difficulty articulating speech (dysarthria)
  • Impairment of speech due to brain damage (aphasia)
  • Reduced and fragmented sleep (insomnia)
  • Brief repeated shock-like spasms of varied muscles within the legs and arms (myoclonus)
  • Eyes misaligned inward or outward (strabismus)
  • Vomiting
  • Malaise or irritability
  • Lethargy
  • Lack of coordination
  • Excessive drooling
  • Rage attacks
  • Decrease in muscle tone
  • Head tilt
  • General feeling of discomfort or illness

These spasms usually appear while trying to move and it worsens with stimulation or agitation but it may also appear while at rest. Myoclonus can make an individual have jerking movements or appear shaky or nervous. Other parts of the body may be involved such as the eyelids, face, head, fingers, trunk, and limbs. Standing or sitting is difficult and almost impossible when the illness worsens.

Almost half of the symptoms of OMS transpire in association with neuroblastoma, cancer that develops from immature nerve cells which usually occurs in infants and children.

The initial symptoms of OMS for most cases begin with an acute outburst of physical symptoms within days or weeks.

Children may appear to be irritable, lethargic or nervous while adults may have encephalopathy or mental clouding.

4Diagnosis

Diagnosis of Opsoclonus-Myoclonus syndrome tends to be slow because it is a rare disease and it occurs at an average age of 18 months.

The diagnosis for OMS is clinical. The antigens for this disease is still unidentified that’s why there are no available diagnostic tests for this. The diagnosis mostly relies on the presence of the characteristic symptoms and signs of OMS. In some occasions, laboratory tests for abnormal white blood cells and/or certain antibodies may also be performed on a suspected patient.

The diagnosis is based on the presence of 3 out of 4 of the following symptoms:

  1. A movement disorder with brief involuntary jerking of a group of muscles caused by muscle contractions (myoclonus) and/or a lack of coordination (ataxia)
  2. Random, repeated, and rapid eye movements in both vertical and horizontal directions (opsoclonus), also known as “dancing eyes”
  3. A rare type of cancer that forms in certain types of the nerve tissue (neuroblastoma)
  4. Sleep and/or behavioral disturbance

Brain MRI in the acute presentation is normal. A detailed MRI is used to detect neuroblastoma which focuses on the whole length para-spinal regions, the mediastinum, the abdomen, the pelvis, the carotids, and the adrenals. Functional tests like metaiodobenzylguanidine scan and urinary vanillylmandelic and homovanillic acid tests are highly recommended but these may produce a negative result because neuroblastoma in OMS is not metabolically active and are typically low grade. Serological tests can help in identifying parainfectious etiology.

There still hasn’t been any consistent neural antibody found in pediatric OMS, unlike in adult OMS where Hu anti-neuronal nuclear bodies have been identified.

Differential diagnosis is also used to distinguish OMS from acute inflammatory cerebellar ataxia which can be differentiated by the absence of irritability, the type of nystagmus or eye movement, and the typically quick recovery without treatment.

To detect OMS in children, infection screening such as lumbar puncture and blood tests and MRI brain scan is performed to exclude the presence of alternative CNS disorders. An MIBG scan and a CT scan of the chest, neck, pelvis with IV and oral contrast, and abdomen need to be performed as well to check for the possibility of an underlying neuroblastoma. On the other hand, to detect OMS in adults, PET scanning is performed. In addition to this, a spinal tap is also necessary to detect neuroinflammation.

Routine tests are done to detect infections. CSF studies are also recommended which includes oligoclonal bands with a paired serum sample, autoantibodies secreted by B cells in the CSF. Immunophenotyping is used for lymphocyte subset analysis which shows an increased frequency of CSF B cells. This is a vital indicator of OMS disease activity. Studies of inflammatory mediators chemokines/cytokines have identified an increase of activators (BAFF) and B-cell attractants (CXCL13) in CSF.

Autoantibodies have been detected in research laboratories for some children affected with OMS. Commercial testing for autoantibody costs a lot that’s why it is only recommended for the atypical cases.

5Treatment

There are currently no known cure or treatment for OMS. There are several drugs however that have been proven to be successful in treating the symptoms of the underlying conditions.

  • ACTH – improves symptoms but can cause incomplete recovery with remaining deficiencies
  • Intravenous Immunoglobulins – produces varying results
  • Rituximab – produces encouraging results
  • Corticosteroids like methylprednisolone or prednisone – used at high dosages (500 mg – 2 g per day for 3 to 5 days) can speed up reversal of symptoms. Gradual tapering with pills is done afterward. A lot of patients require high doses for months to years before tapering.
  • immunosuppressive drugs like azathioprine, cyclophosphamide, immuran, and mycophenolate mofetil – helpful in some cases and in many cases, produces best results with a combination of medications
  • plasmapheresis- used for severe, steroid-unresponsive relapses
  • Trazodone – used for treatment of sleep problems, associated rage attacks, and irritability

These medications are to be taken under a doctor’s prescription and observation. Adults may not respond the same way as children respond to immunological treatment.

The goal of treatment for OMS is to first treat the neuroblastoma and then to strengthen the immune system to reduce the attacks to the cerebellum and prevent any lasting damage.

Chemotherapy or radiotherapy may be effective for neuroblastoma which is needed to be performed before and after surgery. Surgery is done to remove neuroblastoma tumor in children affected by OMS.