Opsoclonus - Clinical Manifestations, Causes, Diagnosis, and Treatment

What Is Opsoclonus?

Opsoclonus refers to the movement disorder of the eye muscles. It leads to irregular, uncontrollable, and multi-directional eye movements, and there is no gap between each eye movement (saccade). Opsoclonus is uncommon and found to occur in one in five million individuals.

What Are the Clinical Manifestations?

The common features in individuals with opsoclonus are as follows:

• Blurred vision.

• Oscillopsia, or unstable vision, is characterized by oscillating visual images of stationary surroundings.

• More prominent eye movements when awake.

• Eye movements remain even after the eyes are closed, in the dark, and during sleep.

What Is the Pathophysiology of Opsoclonus?

The precise mechanism of OMS (opsoclonus myoclonus syndrome) is not well understood, but two main theories have been proposed: the brainstem theory and the cerebellar theory.

1. Brainstem Theory: This theory suggests that the rapid, involuntary eye movements seen in opsoclonus are due to changes in the membrane properties of saccadic burst cells in the brainstem. Under normal conditions, these burst cells are inhibited by omnipause cells. However, when the membrane properties of burst cells are altered, they either become more excitable or experience less inhibition from omnipause cells, leading to eye instability and oscillations.

2. Cerebellar Theory: This theory proposes that opsoclonus occurs due to a lack of inhibition of the oculomotor neurons in the caudal fastigial nucleus of the cerebellum. Specifically, when cerebellar Purkinje cells fail to inhibit the fastigial nucleus, there is increased inhibition of omnipause neurons, allowing saccadic burst neurons to oscillate freely. Histopathological studies support this theory, showing gliosis and inflammation in the cerebellar vermis of individuals with opsoclonus.

Are Opsochoria and Opsoclonus the Same?

Opsochoria is also an eye muscle disorder that generates irregular eye movements without a gap between saccades. Restricted eye movements occur in the horizontal direction in contrast to opsoclonus, in which the eye movement can be vertical, horizontal, or diagonal.

What Is Opsoclonus Myoclonus Syndrome?

Opsoclonus myoclonus syndrome (OMS) is a severe neurological disorder characterized by a generalized tumor, opsoclonus, and disturbances in behavior, sleep, and language. The condition is also called "dancing eyes and dancing feet syndrome." It is more common in infants and young children and affects adults.

What Are the Causes of Opsoclonus?

In adults, opsoclonus can occur due to the following:

• Breast cancer, small cell lung cancer (SCLC), or rarely non-Hodgkin's lymphoma.

• Systemic infections and diseases like HIV (human immunodeficiency virus) and multiple sclerosis.

• Altered response by the immune system to the treatment of Lyme disease or disease caused by hepatitis C, rotavirus, varicella-zoster virus, and others.

• Toxins such as organophosphates, thallium, chlordecone, and others, can cause opsoclonus.

• Drugs like Cocaine, lithium, Amitriptyline, and Phenytoin with Diazepam are also related to opsoclonus occurrence.

• In children, opsoclonus occurs mainly due to underlying extracranial tumors like neuroblastoma, and ganglioneuroma. Rarely a few children get affected with opsoclonus due to hepatoblastoma also.

How Is Opsoclonus Diagnosed?

Opsoclonus is diagnosed in detail for adults and children to exclude the underlying tumors and systemic disorders.

In Adults:

• Computed tomography (CT) imaging with oral or intravenous contrast agents is used to evaluate neurological tumors, especially in children.

• Gadolinium-enhanced magnetic resonance imaging (MRI) of the chest, abdomen, and pelvis to discover any systemic disease and neoplasm is essential.

• Positron emission tomography (PET) is also helpful in assessing disorders in older individuals (above 40 years) that remain undetected by MRI or CT scans.

• Autoantibody testing is a screening test that aids in identifying autoimmune disorders and in diagnosing opsoclonus-myoclonus syndrome. Anti-Ri antibodies are detected from the cerebrospinal fluid obtained through a spinal tap. The immune system produces these antibodies due to neurological disorders and tumors.

In Children:

The evaluation of neuroblastoma is essential as it is interlinked with opsoclonus. It is done by:

• Computed tomography (CT) scan of the entire brain and spinal cord is essential in diagnosing neuroblastoma.

• A urine test to measure the level of Catecholamines is required. The levels are increased in children with neuroblastoma and adrenal gland tumors.

• MIBG (metaiodobenzylguanidine) scintiscan is used to confirm the presence of neuroblastoma and adrenal gland tumors. It is an imaging technique that involves the administration of radioactive material (tracer) to ensure neuroblastoma.

• The antibody screening test detects the anti-neurofilament antibodies that confirm tumors like ganglioneuroma, neuroblastoma, etc.

What Is the Differential Diagnosis?

The symptoms of the following diseases look similar to opsoclonus:

• Wernicke encephalopathy is a neurological disorder caused by a deficiency of Vitamin B1. The patient suffers from memory disturbances, confusion, nystagmus (rapid eye movements), and a lack of muscle control.

• Multiple sclerosis is a chronic neurological disorder that affects the covering of nerves. It causes vision loss, involuntary eye movements, fatigue, lack of coordination, etc.

• Alcohol intoxication occurs in individuals who consume excess alcohol for short periods. It can affect brain functioning and lead to rapid, irregular eye movements, poor coordination, slurred speech, and confusion.

Can Opsoclonus Be Treated?

The management of opsoclonus depends on treating the underlying causes.

In Adults:

• Surgery or radiotherapy is essential in patients diagnosed with neurological and other tumors.

• Medications like corticosteroids that involve oral Prednisone or intravenous administration of Dexamethasone are effective.

• Intravenous immunoglobulin (IVIg) has also shown promising results if combined with steroid therapy.

• Cyclophosphamide, along with steroids or immunoglobulins, effectively treats severe patients.

In Children:

• The use of corticosteroids and immunoglobulins is found effective.

• Cyclophosphamide is given in low doses if the symptoms do not improve with corticosteroids.

What Is the Prognosis for Opsoclonus?

Opsoclonus typically improves with treatment, though it can sometimes recur after seeming to go into remission, particularly with changes in immunotherapy or the onset of new illnesses. Even when opsoclonus resolves, issues with smooth pursuit eye movements often persist for years. Additionally, it is estimated that 60 to 80 percent of patients experience lasting behavioral or psychomotor problems that may worsen over time.

What Are the Complications of Opsoclonus?

• The individual may repeatedly fall due to rapid eye movements and get injured.

• Long-term treatment with corticosteroids can suppress immunity, and the patient may acquire opportunistic infections.

• Delay in development occurs in children with neuroblastoma associated with opsoclonus.

Conclusion:

Prompt evaluation of symptoms like irregular eye movements is critical in diagnosing underlying tumors and systemic diseases. Patient education is necessary to improve the initial check-up with a neuro specialist to assess such symptoms, prevent complications, and improve the quality of life.