Paraneoplastic syndrome is a group of rare autoimmune diseases that can occur due to lung cancer, especially small cell lung cancer (SCLC). The group of diseases occur due to the immune system mistakenly attacking nerve cells.

People living with SCLC may develop paraneoplastic syndrome.

This article has more information about this group of diseases, treatments, and more.

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Paraneoplastic syndrome is a collection of rare diseases. They occur due to an abnormal response from the immune system in response to a cancerous tumor.

They are likely the result of T cells or other antibodies attacking nerve cells in the body.

The National Organization of Rare Disorders (NORD) notes that, in this syndrome, the immune system attacks the brain, nerves, muscles, or spinal cord. The results of the attacks can be temporary or permanent.

Research has shown that SCLC is the most common subtype of lung cancer associated with paraneoplastic syndrome.

SCLC is a neuroendocrine tumor that secretes hormones that can lead to paraneoplastic syndromes.

The term “neuroendocrine” refers to the interactions between the endocrine system and the nervous system. The cells from the tumor release hormones into the blood as a response to stimulation of the nervous system.

Paraneoplastic syndromes more commonly associated with small cell lung cancer include endocrine syndromes and neurologic syndromes.

Endocrine syndromes occur as a result of a release of excess hormones. Neurologic syndromes occur due to the production of antibodies that cause an autoimmune condition.

Other paraneoplastic syndromes include dermatologic and rheumatic syndromes.

The endocrine system consists of hormones and glands throughout the body.

Researchers have shown there are several different types of disorders that can affect the endocrine system. These syndromes include:

Syndrome of inappropriate antidiuretic hormone secretion (SIADH)

Approximately 7% to 16% of those with SCLC will develop SIADH at some point.

With SIADH, a person produces an excessive amount of antidiuretic hormone (ADH). Normally, ADH helps the kidneys control how much water the body loses through the urine. An excess amount of the hormone results in the body retaining too much water and leads to low sodium levels.

Symptoms of SIADH include:

  • falls
  • headache
  • nausea
  • seizures
  • depression
  • muscle cramps
  • lethargy
  • fatigue
  • confusion
  • personality changes

Ectopic Cushing’s syndrome (ECS)

This is the second most common paraneoplastic syndrome that occurs with SCLC, affecting approximately 1% to 5% of cases.

It occurs due to the excess amounts of the adrenocorticotropic hormone (ACTH), which usually controls the production of another hormone called cortisol. Coritsol helps to regulate the metabolism, fight infections, regulate blood sugar levels and respond to stress.

Symptoms of ECS include:

  • a fatty deposit between the shoulders
  • gaining abdominal fat
  • headache
  • muscle weakness
  • changes in mental functions
  • thirst
  • impotence
  • changes in the menstrual cycle

When the immune system cells start to attack the nervous system, including the nerves, brain, or spinal cord, a doctor may diagnose a person with neurologic paraneoplastic syndrome.

These are relatively rare conditions that occur in less than 1% of all people with cancer. About 3% to 5% of people with SCLC will develop this form of paraneoplastic syndrome.

This type of paraneoplastic syndrome often occurs due to the presence of certain antibodies. However, a person may still develop neurological symptoms without the affected antibodies. These syndromes include:

Lambert-Eaten myasthenic syndrome (LEMS)

This is the most common neurologic paraneoplastic syndrome connected to SCLC.

According to the Muscular Dystrophy Association, the immune system attacks the connection between the muscle and the nerves and interferes with the ability of the body to send signals from the nerve cells to the muscle cells.

The immune system attacks the calcium channels on the nerve endings that trigger the release of a chemical called acetylcholine. This chemical normally triggers muscle contraction. The lower levels of acetylcholine mean that there is not enough to cause the muscles to contract normally, resulting in muscle weakness.

Symptoms of LEMS include:

  • muscle weakness in the legs and hips
  • difficulty walking
  • weakness in the upper arms and shoulders
  • dry mouth
  • fatigue
  • constipation

It can also lead to weakness in the eye muscles and those involved with talking and swallowing. However, these symptoms are normally mild.

Myasthenia gravis

Myasthenia gravis occurs due to the presence of anti-acetylcholine antibodies that stop the body from using acetylcholine effectively, which is a neurotransmitter involved in muscle contraction.

The condition affects the muscles that control the:

  • eyelids
  • eyes
  • facial expressions
  • swallowing
  • chewing
  • speaking

Those with myasthenia gravis may experience fatigue and muscle weakness that worsens through the day.

Limbic encephalitis (LE)

There is a strong association between LE and SCLC, with SCLC being present in 40% of LE cases.

Limbic encephalitis causes the limbic areas of the brain to swell and occurs due to the presence of anti-Hu antibodies, which are present in 36% to 50% of cases, and anti-Ma2 antibodies, which are present in 20% of cases.

Symptoms develop over a period of several days to 3 months, and include:

  • personality changes
  • irritability
  • depression
  • memory loss
  • seizures
  • confusion

Cerebella degeneration

Cerebella degeneration occurs when SCLC triggers the production of antibodies that attack brain cells called Purkinje cells. This results in the deterioration of the area of the brain that is connected to balance and muscle coordination.

Symptoms include:

  • weakened muscle coordination in the limbs
  • difficulty with speech
  • difficulty swallowing
  • dementia
  • involuntary eye movements
  • tremors
  • repetitive behaviors

Sensory neuropathy

Sensory neuropathy refers to the neurons located in the dorsal root ganglia. These neurons are found along the sensory nerve roots that are close to the spinal cord. The antibodies typically responsible for sensory neuropathy are anti-Hu antibodies.

Symptoms typically begin on one side and progress to the other side in days or weeks.

A person may experience:

  • pain that is short-lasting and feels similar to an electric shock
  • sensation of walking on sand
  • cold, numbness, or burning in the feet and hands

Sensory neuropathy can also affect a person’s hearing and taste.

Opsoclonus-myoclonus ataxia (OMA)

Healthcare professionals characterize OMA as involuntary and rapid eye movements, uncoordinated movement, sleep disturbance, and irritability.

In adults with SCLC, anti-Hu antibodies target an enzyme called glutamic acid decaroxylase, which converts glutamic acid to GABA, which is a neurotransmitter.

Symptoms include:

  • unsteady and trembling manner of walking
  • sudden, brief, and shock-like muscle spasms
  • rapid eye movement
  • difficulty speaking and swallowing
  • difficulty eating
  • difficulty sleeping
  • lack of coordination
  • decrease in muscle tone

SCLC is typically associated with endocrine and neurological syndromes. However, other paraneoplastic syndromes include:

Rheumatologic syndromes

Rheumatologic syndromes are in the same family as rheumatoid arthritis. One main difference is that rheumatoid arthritis occurs on its own, while these syndromes occur due to the presence of a tumor in the body.

The exact cause is still not known. However, research suggests that megakaryocytes and platelet clumps may be responsible. Megakaryocytes are large bone marrow cells that are necessary for blood clotting.

Dermatologic issues

Certain forms of paraneoplastic issues affect the skin. In some cases, the presence of certain symptoms can be an early sign of lung cancer.

When they occur, the skin condition will typically not respond well to traditional therapies. Instead, the conditions will improve when healthcare professionals treat the tumor.

Symptoms can vary based on the exact underlying condition.

The NORD states there is currently no consensus on the most effective treatment for paraneoplastic syndrome.

However, it states that most practitioners and researchers agree that guiding principles of treatment should include treating the tumor as a first line of therapy along with the use of immune-mediated immunotherapy.

In addition, NORD notes that a doctor should re-screen a person for cancer if they have been in remission and show signs of paraneoplastic syndrome.

Other therapies may include efforts to remove excessive antibodies from the body as well as speech or physical therapy to help regain lost function.

According to the NORD, older adults are more likely than others to develop paraneoplastic syndrome.

Research has shown that the condition can occur in up to 10% of all lung cancer cases, including those living with SCLCr. In fact, in some cases, a person may go in for symptoms of paraneoplastic syndrome before learning they have lung cancer.

The best way to prevent paraneoplastic syndrome is to take steps to limit the likelihood of developing SCLC or other lung cancers.

According to the American Cancer Society, some steps a person can take to help prevent lung cancer include:

  • avoiding tobacco and smoking products
  • limiting exposure to radon
  • eating a healthy diet consisting of a lot of fruits, vegetables, and lean proteins and limited amounts of processed foods
  • limiting or avoiding potential cancer-causing agents in chemicals at home and work if possible

Even when taking these steps, a person can still develop lung cancer. A person should speak with a doctor if they have unexplained symptoms.

There currently is no cure for paraneoplastic syndrome.

Treatment outcome often depends on the following factors:

  • successfully treating the tumor or tumors
  • receiving early therapy for symptoms of the disorder to help prevent further damage
  • at what stage of cancer the syndrome developed

A person should speak with doctor if they have previously had lung cancer and develop unusual symptoms. The development of neurological symptoms could be the result of cancer returning.

In addition, a person should report any changes in symptom intensity or new symptoms to a doctor. It is possible a person may require additional treatment.

A person interested in participating in an investigational study should speak with a doctor first. They may be able to recommend a study or let them know if the person would be a good candidate for research.

Paraneoplastic syndrome is a rare group of disorders that causes nerological damage to the brain, nerves, spinal cord, or muscles.

The condition occurs due to the presence of a malignant tumor, such as small cell lung cancer.

When it occurs, the best treatment is to remove or treat the tumor, attempt to reduce the amount of antibodies in the blood, and provide physical therapy to restore function.

A person should let s doctor know if they develop any unusual symptoms, particularly if they are in remission from cancer.