Paraneoplastic Syndromes

Paraneoplastic syndromes of the nervous system are rare, occurring in less than 1 % of people who have cancer. Other disorders directly related to the cancer, its treatment, tumor spread to other organs (metastases) or infection are more common. Your doctor may perform additional tests to rule out these other disorders before he or she makes a diagnosis of paraneoplastic syndrome.

Paraneoplastic syndromes are a group of rare disorders that develop in some people with cancer, most commonly in people with lung, breast or ovarian cancer. The term "paraneoplastic" means the disorder isn't directly caused by a cancerous tumor, or by its spread to other organs or tissues (metastases). Instead, paraneoplastic syndromes are a result of your body's reaction to the presence of cancer or to substances the tumor produces.

Paraneoplastic syndromes can affect many areas, including your skin, kidneys, blood and joints. But, one of the most common areas affected is the nervous system. Most neurological paraneoplastic syndromes are caused by your immune system's response to a cancerous tumor. Signs and symptoms of paraneoplastic syndromes of the nervous system usually appear when cancer is still in its early stages, often before you even know you have cancer.

By testing your blood and spinal fluid for certain antibodies, doctors can usually determine if your signs and symptoms are caused by a paraneoplastic syndrome. Once a paraneoplastic syndrome has been identified and the cancerous tumor found, treatment of the cancer may eliminate the cause, and signs and symptoms go away. In some cases, treatment of a paraneoplastic syndrome may also require suppressing your immune system.

Signs and symptoms

Signs and symptoms of paraneoplastic syndromes of the nervous system usually develop rapidly and get worse over time. They often begin before diagnosis of a cancer. Specific signs and symptoms depend on the type of disorder you have, but some common signs and symptoms of neurological paraneoplastic syndromes include:

• Difficulty walking
• Difficulty swallowing
• Loss of muscle tone
• Loss of fine motor coordination
• Slurred speech
• Memory loss
• Vision problems
• Sleep disturbances
• Dementia
• Seizures
• Loss of feeling in your arms and legs
• Dizziness

Disorders that may occur as paraneoplastic syndromes of the nervous system include the following:

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Cerebellar degeneration. In this disorder, nerve cells (neurons) in the area of your brain that controls muscle and balance (cerebellum) are affected and die. The most common sign is a wide-legged, unsteady walk, often accompanied by a tremor in the trunk of your body.
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Encephalomyelitis. This condition involves inflammation of your brain and spinal cord and is characterized by headache, delirium, seizures and coma.
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Lambert-Eaton myasthenic syndrome. Muscle weakness, fatigue, swallowing difficulty and vision changes are the most frequent signs and symptoms of this disorder, which is caused by disrupted communication between your nerves and muscles.
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Limbic encephalitis. In this disorder, portions of your brain swell, which can cause memory loss, drowsiness, confusion, disorientation and seizures, among other signs and symptoms.
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Myasthenia gravis. This disorder is characterized by weakness and rapid fatigue of any of the muscles under your voluntary control, including those in your face, eyes, arms and legs, and muscles involved in chewing, swallowing and talking. Muscles that control breathing also may be involved. This may be associated with a tumor of the thymus gland (thymoma).
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Neuromyotonia. This condition — also known as Isaacs' syndrome — is characterized by abnormal nerve impulses from the motor neurons of your peripheral nerves. These impulses cause twitching, progressive stiffness, muscle cramps and slowed movement, among other signs and symptoms.
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Neuropathies. Neuropathy is damage to your nerves. Paraneoplastic syndromes may include autonomic neuropathy (damage to the nerves that regulate the body functions you can't control, such as heart rate, blood pressure, perspiration and digestion) and sensory neuropathy (damage to sensory nerves in your peripheral nervous system, which include nerves in your face, arms, legs, torso and some nerves in your skull).
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Opsoclonus-myoclonus. Rapid, irregular eye movements (opsoclonus) coupled with quick involuntary muscle jerks (myoclonus) can result from damage to your nervous system.
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Stiff-person syndrome. This disabling neurological disorder is characterized by progressive, severe muscle stiffness or rigidity, mainly in your spine and legs. It may also cause painful muscle spasms.

Causes

Paraneoplastic syndromes occur in people who have cancer. In the nervous system, these syndromes are usually caused by cancer-fighting antibodies or white blood cells, known as T cells, that your body activates to combat the cancer. Instead of attacking only the cancer cells, the antibodies attack normal cells in your brain and nervous system as well. As a result, paraneoplastic syndromes can develop. Rarely, paraneoplastic syndromes of the nervous system may be caused by hormones or other chemicals that the cancerous tumor secretes.

Risk factors

Neurological paraneoplastic syndromes are most common in people who have lung, breast or ovarian cancer. Most often, they're the result of your immune system's response to cancer. But, it's not clear why this response occurs in some people who have cancer and not in others. Doctors have not found any risk factors that increase your chances of developing a neurological paraneoplastic syndrome if you have cancer.

When to seek medical advice

The signs and symptoms of most neurological paraneoplastic syndromes start suddenly and progress rapidly over several weeks or months. Your specific signs and symptoms will depend on the type of paraneoplastic syndrome you have. If you experience any of the following, call your doctor for an appointment:

• Difficulty walking
• Difficulty swallowing
• Loss of muscle tone
• Loss of fine motor coordination
• Slurred speech
• Memory loss
• Vision problems
• Sleep disturbances
• Dementia
• Seizures
• Loss of feeling in your arms and legs
• Dizziness

Screening and diagnosis

The signs and symptoms of a paraneoplastic syndrome of the nervous system usually appear before cancer has been found, making diagnosis difficult. If your doctor suspects you have a neurological paraneoplastic syndrome, he or she may recommend the following:

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Blood test. A blood test may reveal paraneoplastic antibodies in your blood serum, although it's possible to have one of these syndromes and not have the antibodies in your blood.
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Spinal tap (lumbar puncture). During a lumbar puncture, a needle is inserted into your lower spine to extract a small amount of cerebrospinal fluid (CSF) — the fluid that protects your brain and spinal cord from injury — for laboratory analysis. Sometimes, paraneoplastic antibodies may be present in CSF fluid even if they're not noticeable in your blood.
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Radiology tests. Computerized tomography (CT), magnetic resonance imaging (MRI) or positron emission tomography (PET) scans provide images that your doctor may use to detect cancer. In many cases, however, the cancer causing a neurological paraneoplastic syndrome is small and slow-growing, making it difficult to find.

Tests that can help your doctor determine if your brain, spinal cord or nerves are damaged may also aid in the diagnosis of your specific disorder. These tests may include:

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Magnetic resonance imaging (MRI). MRI is a technique that uses a magnetic field and radio waves to create cross-sectional images of your head and body. MRI often helps with the diagnosis of central nervous system disorders because it produces such high-resolution images of the brain and spinal cord.
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Electromyography (EMG). EMG measures the electrical discharges produced in muscles. A thin needle electrode is inserted into the muscle or nerve your doctor wants to study. An instrument records the electrical activity in your muscle at rest and as you contract the muscle. The size, duration and frequency of these signals help determine if there's damage to the muscle or to the nerves leading to the muscle.
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Electroencephalography (EEG). This procedure records the electrical activity of your brain. Between 16 and 30 small electrodes may be attached to your scalp with paste or an elastic cap. The electrodes pick up the electrical impulses from your brain and send them to the EEG machine, which records your brain waves.

Complications

Signs and symptoms of neurological paraneoplastic syndromes may decrease or stop once you have received treatment for your cancer. If, however, you have a paraneoplastic syndrome that has destroyed neurons, such as in cerebellar degeneration, that damage usually cannot be reversed and, in some cases, it may result in permanent disability.

Treatment

Treatment of neurological paraneoplastic syndromes involves treating the cancer and, in some cases, decreasing or stopping the immune response that's causing the neurological signs and symptoms. Your treatment will depend on the specific type of paraneoplastic syndrome you have, but it may include:

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Cancer treatment. Depending on your diagnosis, chemotherapy, radiation or surgery may be necessary to treat your cancer.
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Medication. Your doctor may prescribe medications to stop your immune system from damaging your nerves. These may include corticosteroids, cyclophosphamide (Cytoxan) or tacrolimus (Prograf).
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Plasmapheresis. This process — also known as plasma exchange — removes the fluid part of the blood, called plasma, from your blood cells with a device known as a cell separator. The red and white blood cells, along with your platelets, are returned to your body, while the plasma, which contains unwanted paraneoplastic antibodies, is discarded and replaced with other fluids.
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Intravenous immunoglobulin (IVIg). Immunoglobulin contains healthy antibodies from blood donors. High doses of immunoglobulin can block the damaging antibodies in your blood.

Physical therapy. Physical, occupational or speech therapy may be necessary to help you regain some of your muscle and nerve functions.

Coping skills

Everyone has his or her own way of coping with cancer. But, you don't have to do it alone. If you have questions or would like guidance, talk with a member of your health care team. Also consider the following steps to help you deal with your diagnosis:

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Find out all you can about your condition. Ask your doctor questions. Ask members of your health care team to recommend resources where you can get more information. The more you know about your condition, the better you're able to participate in decisions about your care.
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Talk to others. Support groups for people with paraneoplastic syndromes can put you in touch with others who have faced the same challenges you're facing. Ask your doctor about groups in your area. Paraneoplastic syndromes are rare, though, so you may need to connect with people outside your immediate area.
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Take care of yourself. Do what you can to maintain a healthy lifestyle. Choose healthy meals with plenty of fruits and vegetables. When you feel up to it, work light exercise into your daily routine. Cut extra stress out of your life when possible. Get plenty of sleep so that you feel rested when you wake up. Take care of your body and mind so that you're better able to stick to your treatment plan.

Courtesy of: Mayo Clinic