What causes paraneoplastic syndrome?

Paraneoplastic syndromes are diverse and their biology is not fully understood. Paraneoplastic neurological syndrome seems to occur when proteins on the surface of cancer cells are also present on normal brain and nerve cells.

When the body mounts an immune response to the tumour cells, the antibodies and immune cells produced then also attack the nervous system, causing progressive nerve damage.

Autoimmune paraneoplastic syndromes are most common in people with lung, breast, ovarian or lymphatic cancers and can sometimes be diagnosed by identifying antibodies in their serum that are active against nerve tissue.

Other paraneoplastic syndromes arise when a tumour secretes hormones, enzymes or other physiologically active substances, or when other substances produced by the tumour interfere with metabolic functions.

Some small cell lung cancers, for example, produce a hormone that causes the kidneys to retain water. The paraneoplastic syndrome that develops causes immediate and serious symptoms.

Neurological symptoms of paraneoplastic syndrome

Neurological symptoms of paraneoplastic syndrome can develop over days or weeks and can include:

• Walking, balance or speech difficulties.
• Slurring words and mispronouncing words.
• Finding it hard to swallow properly.
• Not being able to coordinate movement and having muscle weakness.
• Feeling dizzy or experiencing vertigo when standing.
• Losing sensation in the skin of the arms and legs.
• Finding it difficult to remember things.
• Trouble getting to sleep and waking often.
• Seizures or convulsions.
• Confusion and dementia.
• Poor eyesight that gets worse.

These neurological problems often appear before the cancer is detected: in some cases of paraneoplastic syndrome a tumour is never found, perhaps because the antibodies that develop against nerve tissue prevent its growth.

Types of paraneoplastic neurological syndrome

There are many types of paraneoplastic neurological syndrome and examples include:

• Lambert-Eaton myasthenic syndrome in which muscles around the hip and shoulder become weak. Swallowing and vision may also be affected. This form of paraneoplastic syndrome is often associated with lung cancer.
• Myasthenia gravis produces severe muscle weakness, sometimes causing breathing difficulties.
• Cerebellar degeneration causes loss of balance, unsteady limb movements and problems with speech and swallowing.
• Limbic encephalitis is a paraneoplastic syndrome that involves swelling of the brain, often causing depression, seizures and irritability.
• Sensory neuropathy involves progressive loss of skin sensation in the limbs.
• Stiff person syndrome in which muscles, particularly in the legs and spine, become stiff or rigid.

Opsoclonus-myoclonus syndrome is a type of paraneoplastic syndrome that is sometimes associated with neuroblastoma in children. It involves rapid irregular eye movements with muscle jerks and poor coordination.

These conditions are extremely rare: together they affect less than 1% of cancer patients. Lambert-Eaton myasthenic syndrome may develop in about 1% of people with small cell lung cancer.