Paraneoplastic syndromes of the nervous system

DEFINITION

Paraneoplastic syndromes of the nervous system are a group of rare disorders that develop in some people who have cancer. Paraneoplastic syndromes of the nervous system are the most commonly reported paraneoplastic syndromes, but these syndromes can also affect other organ systems including hormone (endocrine), skin (dermatologic), blood (hematologic) and joints (rheumatologic).

Paraneoplastic events may also in part explain some of the most common symptoms of cancer, such as fatigue, loss of appetite for food (anorexia) and weight loss.

Paraneoplastic syndromes of the nervous system occur when cancer-fighting agents of the immune system also attack parts of the brain, spinal cord, peripheral nerves or muscle. Cancers commonly associated with these disorders include lung, breast and ovarian, as well as cancers of the blood. In most cases, paraneoplastic syndromes of the nervous system occur before a cancer is diagnosed.

Depending on the component of the nervous system affected, paraneoplastic syndromes can cause problems with muscle movement or coordination, sensory perception, memory or thinking skills, or even sleep.

Sometimes the injury to the nervous system is reversible with therapy directed toward the cancer and the immune system. However, these diseases can also rapidly result in severe damage to the nervous system which can’t be reversed. Regardless, treatment of the underlying cancer and other interventions may prevent further damage, improve symptoms and give you a better quality of life.

CAUSES

Paraneoplastic syndromes are not caused by cancer cells directly disrupting nerve function, by the cancer spreading (metastasis), or by other complications such as infections or treatment side effects. Instead, they occur alongside the cancer as a result of the activation of your immune system.

Researchers believe paraneoplastic syndromes are caused by cancer-fighting abilities of the immune system, particularly antibodies and certain white blood cells, known as T cells. Instead of attacking only the cancer cells, these immune system agents also attack the normal cells of the nervous system and cause neurological disorders.

Other cancer-related neurological problems

Other neurological problems may be related to cancers. For example, tumors may develop in your brain or spinal cord. Non-nervous system tumors can cause tissue injury that results in injury to the nervous system. For example, a tumor may compress a nerve or the spinal cord.

Cancers cells may migrate away from the main area of growth (metastasize) to other areas of the body. Malignant cells from your lungs, for example, may metastasize to your brain.

Also, cancer treatments such as radiation therapy and chemotherapy can affect neurological function. However, these complications of cancer aren’t considered paraneoplastic syndromes, even though they may produce similar signs and symptoms.

SYMPTOMS

Signs and symptoms of paraneoplastic syndromes of the nervous system usually develop relatively quickly, often over days to weeks. Signs and symptoms vary depending on the body part being injured, and may include:

• Difficulty walking
• Difficulty maintaining balance
• Loss of muscle coordination
• Loss of muscle tone or weakness
• Loss of fine motor skills, such as picking up objects
• Difficulty swallowing
• Slurred speech
• Memory loss and other thinking (cognitive) impairment
• Vision problems
• Sleep disturbances
• Seizures
• Sensory disturbances
• Unusual involuntary movements

Types of paraneoplastic syndromes

Some symptoms of these disorders often occur in patterns or clusters which are seen as a recognizable syndrome. When these syndromes clearly co-occur with a cancer, they are designated as paraneoplastic syndromes.

Sometimes, very similar neurological disorders may result from an immune system disease process unrelated to cancer. Therefore, neurological disorders are identified as paraneoplastic syndromes only when there is a definite or probable association with cancer.

Common paraneoplastic syndromes of the nervous system include:

• Cerebellar degeneration. This is the loss of nerve cells in the area of the brain that controls muscle functions and balance (cerebellum). Signs and symptoms may include unsteady or impaired walking, lack of muscle coordination in your limbs, inability to maintain your trunk posture, dizziness, nausea, involuntary eye movement, double vision, difficulty speaking, or difficulty swallowing.
• Limbic encephalitis. This is inflammation affecting a region of the brain known as the limbic system, which controls emotions, behaviors and certain memory functions. People with this disorder may experience personality changes or mood disturbances, memory loss, seizures, hallucinations, or sleep disturbances.
• Encephalomyelitis. This syndrome refers to inflammation of the brain and spinal cord. There may be a wide variety of symptoms and signs depending on the area affected.
• Opsoclonus-myoclonus. This syndrome is due to dysfunction of the cerebellum or its connections. It can cause rapid, irregular eye movements (opsoclonus) and involuntary, chaotic muscle jerks (myoclonus) in your limbs and trunk.
• Stiff person syndrome. Previously called stiff man syndrome, this syndrome is characterized by progressive, severe muscle stiffness or rigidity, mainly affecting your spine and legs. It may also cause painful muscle spasms.
• Myelopathy. This term refers to a syndrome of injury limited to the spinal cord. It sometimes is called transverse myelitis. Depending on the level of spinal cord injury, you may have changes in bowel and bladder function, and severe weakness and numbness up to a certain level in your body. If the level of injury includes your neck, you can have severe disability affecting all four limbs.
• Lambert-Eaton myasthenic syndrome. This is a syndrome caused by disrupted communication between nerves and muscles. Signs and symptoms include muscle weakness, fatigue, difficulty swallowing, difficulty speaking, irregular eye movement and double vision. Autonomic nervous system problems can include dry mouth, impotence and failure to sweat.

  When it occurs as a paraneoplastic syndrome, Lambert-Eaton syndrome is typically associated with lung cancer.

• Myasthenia gravis. Myasthenia gravis is also related to disrupted communication between nerves and muscles and also characterized by weakness and rapid fatigue of any of the muscles that are under voluntary control, including muscles in your face, eyes, arms and legs. The muscles involved in chewing, swallowing, talking and breathing may be affected as well.

  When myasthenia gravis occurs as a paraneoplastic syndrome, it is typically associated with cancer of the thymus gland (thymoma).

• Neuromyotonia. Neuromyotonia — also known as Isaacs syndrome and peripheral nerve hyperexcitability — is characterized by abnormal impulses in nerve cells outside the brain and spinal cord (peripheral nerves) that control muscle movement. These impulses can cause twitching, muscle rippling that looks like a “bag of worms,” progressive stiffness, muscle cramps, slowed movement and other muscle impairments.
• Peripheral neuropathy. This condition refers to patterns of damage to nerves that transmit messages from the brain or spinal column to the rest of your body. When damage involves only the sensory nerves of the peripheral nervous system, you can have pain and disturbances in sensation anywhere in your body.
• Dysautonomia. Dysautonomia refers to a wide range of signs and symptoms resulting from injury to the nerves that regulate nonvoluntary body functions (autonomic nervous system), such as heart rate, blood pressure, sweating, and bowel and bladder functions. When this part of the nervous system is affected, the most common symptoms are low blood pressure and nausea, bloating, and weight loss.

When to see a doctor

The signs and symptoms of paraneoplastic syndromes of the nervous system are similar to those of many conditions. If you have any signs or symptoms suggesting a paraneoplastic syndrome, see your doctor as soon as possible. Early diagnosis and appropriate care can be extremely important.