Paraneoplastic syndromes of the nervous system

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1 Paraneoplastic syndromes of the nervous system Title: Neurology Nervous System Source: Mayo Clinic Link: Paraneoplastic syndromes of the nervous system are a group of rare disorders that develop in some people with cancer. Paraneoplastic syndromes of the nervous system occur when cancer-fighting agents of the immune system attack nerve or muscle cells. Cancers commonly associated with these disorders include lung, breast and ovarian cancer. Depending on the location of the cell damage, these syndromes can cause problems with muscle movement or coordination, sensory perception, memory or thinking skills, or sleep. In cases where extensive cell damage has occurred, paraneoplastic syndromes of the nervous system can't be reversed. However, treatment of the underlying cancer and other interventions may prevent further damage, improve symptoms and result in better quality of life. Symptoms Signs and symptoms of paraneoplastic syndromes of the nervous system usually develop relatively quickly, over weeks to months. Problems vary, depending on the site of nerve damage, 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 Vision problems Spinning sensations (vertigo) or dizziness Sleep disturbances Dementia

2 Seizures Numbness, tingling or sensory loss in arms and legs Types of paraneoplastic syndromes Several different nervous system (neurological) disorders may occur as paraneoplastic syndromes. Each disorder is characterized by nerve damage at particular sites and by certain signs and symptoms. Also, each of these neurologic disorders may result from a disease mechanism unrelated to cancer. Neurologic 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 the following disorders: Cerebellar degeneration 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 the limbs, inability to maintain posture of the trunk, dizziness, nausea, involuntary eye movement, double vision, difficulty speaking, or difficulty swallowing. Limbic encephalitis 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 is inflammation of the brain and spinal cord. Initial problems may include sensory loss or numbness, but they progress rapidly to include signs and symptoms of cerebellar degeneration or limbic encephalitis. Dysfunction also occurs in the autonomic nervous system, which regulates nonvoluntary body systems. For example, problems may include irregular heartbeats, low blood pressure or respiratory failure. Opsoclonus-myoclonus, which disrupts function of the cerebellum, can cause rapid, irregular eye movements (opsoclonus) and involuntary, chaotic muscle jerks (myoclonus) in both the limbs and trunk. Stiff man syndrome, or stiff person syndrome, is characterized by progressive, severe muscle stiffness or rigidity, mainly affecting the spine and legs. It may also cause painful muscle spasms. Lambert-Eaton myasthenic syndrome is 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 problems can include dry mouth, impotence and failure to sweat. Myasthenia gravis is characterized by weakness and rapid fatigue of any of the muscles that are under voluntary control, including muscles in the face, eyes, arms and legs. The muscles involved in chewing, swallowing, talking and breathing may be affected as well. Neuromyotonia also known as Isaac's syndrome 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.

3 Peripheral neuropathy is damage to nerves that transmit messages from the brain or spinal column to the rest of the body. Paraneoplastic syndromes may include damage to the nerves that regulate non-voluntary body functions, such as heart rate, blood pressure, perspiration, and bowel and bladder functions (autonomic neuropathy), as well as damage to sensory nerves in the peripheral nervous system, including nerves to the face, eye muscles, throat, arms, legs and torso (sensory neuropathy). When to see a doctor The signs and symptoms of paraneoplastic syndromes of the nervous system are not specific to these disorders. They may be an indication of any number of conditions. If you have any problems suggesting a paraneoplastic syndrome, see your doctor as soon as possible for a diagnosis and appropriate care. Causes Paraneoplastic syndromes occur among a small percentage of people who have cancer, but these syndromes aren't caused by cancer cells directly disrupting nerve function. Instead, they're believed to be caused by cancer-fighting antibodies or certain white blood cells, known as T cells, that the body activates to combat the cancer. Instead of attacking only the cancer cells, these immune system agents also attack normal cells of the nervous system. Other cancer-related neurological problems Other neurological problems may be related to cancers. For example, cancerous (malignant) tumors may develop in the brain or spinal cord, or tumors in other tissues may disrupt local nerve function. Cancers elsewhere in the body may migrate (metastasize). Malignant cells from the lungs, for example, may metastasize to the brain. Also, treatments for cancer can affect neurological function. These complications of cancer aren't considered paraneoplastic syndromes, even though they may produce similar signs and symptoms. Risk factors Any cancer may be associated with a paraneoplastic syndrome of the nervous system. However, the disorders occur more often in people with cancers of the lung, ovary, breast, testis or lymphatic system.

4 Preparing for your appointment Most people with paraneoplastic syndrome experience neurological problems before there is a diagnosis of cancer or any indication of cancer. So, you're likely to start by seeing your primary care doctor about your symptoms. You may then be referred to a specialist in nervous system disorders (neurologist) or a cancer specialist (oncologist). Questions from your doctor Depending on the type and severity of symptoms, it may be important for a friend or family member to be at the appointment to help answer questions and to provide moral support. Be prepared to answer the following questions: Have you experienced any muscle weakness or lack of coordination? Have you experienced any unusual or involuntary muscle movements? Have you had any unusual vision problems? Do you have any problems chewing, swallowing or speaking? Do you have any difficulty breathing? Have you had any seizures? How long have they lasted? Have you experienced dizziness or nausea? Do you have trouble sleeping, or have your sleep patterns changed? Are you having difficulty performing everyday tasks with your hands? Have you experienced any numbness or tingling in your limbs? Have you experienced a significant change in mood? Have you been seeing or hearing things that others are not aware of? Have you had any memory problems? When did the symptoms begin? Have the symptoms worsened since you first noticed them? Have you been diagnosed with cancer? What medications do you take, including over-the-counter drugs and dietary supplements? What is the daily dosage of each? Have any close relatives had cancer? If so, what types of cancer? Have you ever smoked? Questions for your doctor Questions you may want to ask your doctor include: What diagnostic tests are you going to order? Which specialists will I need to see? What is the likely time frame for completing tests and getting results? How will you communicate results to me? What things are you looking for with the tests? What conditions are you trying to rule out?

5 Tests and diagnosis In a diagnostic workup for assessing neurological problems that could indicate a paraneoplastic syndrome, your doctor is trying to answer the following general questions: What neurological problems are present? Is there evidence of cancer underlying these problems? What other condition might be causing the problems? Clinical exam Your doctor or a neurologist will conduct a general physical, as well as a neurological exam. He or she will ask you questions and conduct relatively simple tests in the office to judge: Reflexes Muscle strength Muscle tone Sense of touch Vision and hearing Coordination Balance Mental status Mood Laboratory tests Laboratory tests will likely include: Blood tests. A nurse or technician may draw a blood sample for laboratory tests. These tests may identify antibodies commonly associated with paraneoplastic syndromes. However, a person may carry suspect antibodies without having a paraneoplastic syndrome, and a person with the disorder may not carry the suspect antibodies. Lab tests may also identify an infection, a hormone disorder or a disorder in nutrient processing (metabolic disorder) that could be causing symptoms. Spinal tap (lumbar puncture). During a lumbar puncture, a neurologist or nurse inserts a needle into your lower spine to extract a small amount of cerebrospinal fluid (CSF) the fluid that cushions your brain and spinal cord for laboratory analysis. Sometimes, paraneoplastic antibodies may be present in CSF fluid when they're not detectable in your blood. Imaging tests Imaging tests are used to locate a cancerous tumor that may be the underlying problem or to

6 identify other factors causing the neurological symptoms. One or more of the following tests may be used: Computerized tomography (CT) is a specialized X-ray technology that produces thin, cross-section images of tissues. Magnetic resonance imaging (MRI) uses a magnetic field and radio waves to create detailed cross-sectional or 3-D images of your body's tissue. Positron emission tomography (PET) uses radioactive compounds injected into your bloodstream to produce cross-sectional or 3-D images of the body. They can be used to identify tumors, measure metabolism in tissues, show blood flow and locate brain abnormalities related to seizures. PET-CT, a combination of PET and CT, may increase the detection rate of small cancers, common in those with paraneoplastic neurological disorders. If no malignant tumor is located or no other cause identified, the problem may be a tumor that's still too small to find. You'll likely have follow-up imaging tests every three to six months for a few years or until a cause is identified. Treatments and drugs Treatment of neurological paraneoplastic syndromes involves treating the cancer and, in some cases, suppressing 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 the following options. Medications In addition to drugs, such as chemotherapy, to combat your cancer, your doctor may prescribe one or more of the following drugs to inhibit immune system attacks on the nervous system: Corticosteroids, such as prednisone, inhibit inflammation. Long-term use of corticosteroids may cause weakening of the bones (osteoporosis), diabetes, high blood pressure, high cholesterol and other serious side effects. Immunosuppressants inhibit the production of disease-fighting white blood cells. Side effects include an increased risk of infections. Drugs with immunosuppressant properties that may be used include azathioprine (Imuran) and cyclophosphamide (Cytoxan). Depending on the type of neurological syndrome and symptoms, other medications may include: Anti-seizure medications may help control seizures associated with syndromes affecting nerve cells in the brain. A number of anti-seizure medications are available, including carbamazepine (Tegretol, Carbatrol, others) and valproic acid (Depakene, Stavzor). Medications to enhance nerve to muscle transmission may improve symptoms of syndromes affecting muscle function. Some drugs, such as 3,4-diaminopyridine, enhance

7 the release of a chemical messenger that transmits a signal from nerve cells to muscles. Other drugs, such as pyridostigmine (Mestinon, Regonol), prevent the breakdown of these chemical messengers. Other medical treatments Other treatments that may improve symptoms include: Plasmapheresis. This process also known as plasma exchange separates 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 antibodies, is discarded and replaced with other fluids. Intravenous immune globulin (IVIg). Immune globulin contains healthy antibodies from blood donors. High doses of immune globulin accelerate the destruction of damaging antibodies in your blood. Other therapies Other therapies may be helpful if a paraneoplastic syndrome has caused impairments that disrupt functional abilities: Physical therapy. Specific exercises may help you regain some muscle function that may have been damaged. Speech therapy. If a paraneoplastic syndrome has affected your ability to speak or swallow, a speech therapist can help you relearn muscle control necessary for speech, chewing and eating. Coping and support Many people with cancer benefit from education and resources designed to improve coping skills. If you have questions or would like guidance, talk with a member of your health care team. The more you know about your condition, the better you're able to participate in decisions about your care. Support groups can put you in touch with others who have faced the same challenges you're facing. If you can't find an appropriate support group where you live, you might find one on the Internet. March 3, Mayo Foundation for Medical Education and Research (MFMER). All rights reserved. A single copy of these materials may be reprinted for noncommercial personal use only. "Mayo," "Mayo Clinic," "MayoClinic.com," "EmbodyHealth," "Enhance your life," and

8 the triple-shield Mayo Clinic logo are trademarks of Mayo Foundation for Medical Education and Research. Privacy policy (Updated Nov. 5, 2010) Terms and conditions of use policy (Updated July 8, 2010) Mayo Foundation for Medical Education and Research. All rights reserved.

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