Paraneoplastic syndromes of the nervous system

February, 20th, 2024

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Paraneoplastic syndromes of the nervous system are a group of rare conditions that develop in some people who have cancer. In addition to the nervous system, paraneoplastic syndromes also can affect other organ systems including hormones, skin, blood and joints.

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.

Depending on where the nervous system is affected, paraneoplastic syndromes can affect muscle movement, coordination, sensory perception, memory, thinking skills or even sleep.

Sometimes the injury to the nervous system can be reversed with therapy directed toward the cancer and the immune system. But sometimes paraneoplastic syndromes can result in permanent damage to the nervous system.

Treating the cancer and other therapies may prevent further damage and improve symptoms and quality of life.

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Symptoms

Symptoms of paraneoplastic syndromes of the nervous system can develop relatively quickly, often over days to weeks. They often begin even before a cancer is diagnosed.

Symptoms vary depending on the body part being injured, and may include:

• Trouble walking.
• Trouble with balance.
• Loss of muscle coordination.
• Loss of muscle tone or weakness.
• Loss of fine motor skills, such as picking up objects.
• Trouble swallowing.
• Slurred speech or stuttering.
• Memory loss and other thinking impairment.
• Vision changes.
• Trouble sleeping.
• Seizures.
• Hallucinations.
• Movements that can’t be controlled.

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Types of paraneoplastic syndromes

Examples of paraneoplastic syndromes of the nervous system include:

• Cerebellar degeneration, also known as cerebellar ataxia. In this syndrome, loss of nerve cells occurs in the area of the brain called the cerebellum that controls muscle functions and balance. Symptoms may include trouble walking, lack of coordination in the arms and legs, trouble maintaining posture, and dizziness. They also may include nausea, eye movements that can’t be controlled, double vision, trouble speaking or trouble swallowing.
• Limbic encephalitis. This syndrome involves swelling, known as inflammation, of an area of the brain known as the limbic system. The limbic system controls emotions, behaviors and certain memory functions. People with this condition may experience personality changes or mood changes, memory loss, seizures, hallucinations, or drowsiness.
• Encephalomyelitis. This syndrome refers to inflammation of the brain and spinal cord. There may be a wide variety of symptoms depending on the area affected.
• Opsoclonus-myoclonus. This syndrome occurs when the cerebellum or its connections don’t work properly. It can cause rapid, irregular eye movements and muscle jerks in the arms, legs and trunk.
• Stiff person syndrome. Previously called stiff man syndrome, this syndrome leads to serious muscle stiffness, known as rigidity, that gets worse over time. Stiffness mainly affects the spine and legs. It also may cause painful muscle spasms.
• Myelopathy. This term refers to a syndrome that involves injury to the spinal cord. Symptoms depend on the level of spinal cord injury. Symptoms may include changes in bowel and bladder function, and weakness and numbness up to a certain level in the body. If the level of injury includes the neck, it can cause a serious disability that affects the arms and legs.

• Lambert-Eaton myasthenic syndrome. This syndrome is caused by disrupted communication between nerves and muscles. Symptoms include muscle weakness in the pelvis and legs, and fatigue. It also may cause trouble swallowing and speaking, irregular eye movement, and double vision. Other symptoms may include dry mouth and erectile dysfunction.

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

• Myasthenia gravis. Myasthenia gravis also is related to disrupted communication between nerves and muscles. People with myasthenia gravis have weakness and rapid fatigue of any of the muscles that are under voluntary control. These include muscles in the 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, known as thymoma.

• Neuromyotonia, also known as Isaacs’ syndrome. Neuromyotonia occurs when there are an excess number of nerve impulses that control muscle movement. This is known as peripheral nerve hyperexcitability. These impulses can cause twitching, muscle rippling that looks like a “bag of worms” and stiffness that gets worse over time. It also may cause muscle cramps, slowed movement and other issues with the muscles.
• Peripheral neuropathy. In this condition, nerves that transmit messages from the brain or spinal column to the rest of the body are damaged. These nerves are known as peripheral nerves. When damage involves only the sensory nerves, it causes pain and changes in sensation anywhere in the body.
• Dysautonomia. Dysautonomia refers to a wide range of symptoms that result from injury to the nerves that regulate involuntary body functions. Known as the autonomic nervous system, these nerves control heart rate, blood pressure, sweating, and bowel and bladder functions. Symptoms may include low blood pressure, irregular heartbeats and trouble breathing.

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When to see a doctor

Symptoms of paraneoplastic syndromes of the nervous system are similar to those of many conditions, including cancer, cancer complications and some cancer treatments.

But if you have any symptoms suggesting a paraneoplastic syndrome, see your healthcare professional as soon as possible. Early diagnosis and appropriate care are important for treating the cancer and preventing further damage of the nervous system.

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Causes

Paraneoplastic syndromes of the nervous system are not caused by cancer cells directly or by the cancer spreading, known as metastasis. They’re also not caused by other complications, such as infections or treatment side effects. Instead, the syndromes occur alongside the cancer as a result of the activation of your immune system.

Researchers believe that paraneoplastic syndromes of the nervous system are caused by cancer-fighting abilities of the immune system. In particular, antibodies and certain white blood cells, known as T cells, are thought to be involved. Instead of attacking only the cancer cells, these immune system agents also attack the healthy cells of the nervous system.

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Risk factors

Any cancer may be associated with a paraneoplastic syndrome of the nervous system. However, it occurs more often in people with cancers of the lung, ovary, breast, testis or lymphatic system.

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Diagnosis

To diagnose paraneoplastic syndrome of the nervous system, you may need a physical exam and blood tests. You also may need imaging tests or a spinal tap, also known as a lumbar puncture.

Because paraneoplastic syndromes of the nervous system are associated with cancer, you may need certain cancer screening tests based on your age.

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Clinical exam

Your healthcare professional or a neurologist conducts a general physical and a neurological exam. You’re asked questions and your healthcare professional conducts simple tests in the office to judge your:

• Reflexes.
• Muscle strength.
• Muscle tone.
• Sense of touch.
• Vision and hearing.
• Coordination.
• Balance.
• Mood.
• Memory.

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Laboratory tests

Laboratory tests may include:

• Blood tests. You may have blood drawn for a number of tests, including tests to pinpoint antibodies commonly associated with paraneoplastic syndromes of the nervous system. Other tests may help diagnose an infection, a hormone condition or a condition in processing nutrients, known as a metabolic condition.

• Spinal tap, also known as a lumbar puncture. During a spinal tap, a sample of cerebrospinal fluid (CSF) is taken. CSF cushions your brain and spinal cord. A neurologist or specially trained nurse inserts a needle into your lower spine to remove a small amount of CSF for analysis.

  Sometimes paraneoplastic antibodies are found in CSF but they can’t be seen in your blood. If these antibodies are found in both your CSF and blood, it provides strong evidence that a paraneoplastic syndrome is causing the symptoms.

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Imaging tests

Imaging tests are used to find a tumor or other causes of your symptoms. One or more of the following tests may be used:

• Computerized tomography (CT) is a specialized X-ray technology that produces thin, cross-sectional images of tissues.
• Magnetic resonance imaging (MRI) uses a magnetic field and radio waves to create detailed cross-sectional or 3D images of your body’s tissue.
• Positron emission tomography (PET) uses radioactive compounds injected into your bloodstream to produce cross-sectional or 3D images of the body. PET scans can be used to identify tumors, measure metabolism in tissues, show blood flow and locate brain changes related to seizures.
• PET plus CT, a combination of PET and CT, may help find small cancers. Small cancers are common in people who have paraneoplastic neurological disorders.

If tests don’t find a cancerous tumor or another cause of your symptoms, you might have a tumor that is still too small to find. The tumor may be causing a powerful response from the immune system that is keeping it very small. Your healthcare professional likely will recommend that you have follow-up tests every 3 to 6 months until a cause is found.

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Treatment

Treatment of paraneoplastic syndromes of the nervous system involves treating the cancer. Sometimes treatment also involves suppressing the immune response that’s causing your symptoms. Your treatment depends on the type of paraneoplastic syndrome you have. It may include the following options.

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Medications

In addition to cancer treatments, such as chemotherapy, your healthcare professional may prescribe one or more medicines. These medicines can help stop your immune system from damaging your nervous system:

• Corticosteroids, such as prednisone, inhibit inflammation. These medicines can have serious long-term side effects. Corticosteroids may lead to type 2 diabetes, high blood pressure, high cholesterol and weakened bones, known as osteoporosis. The medicine also can cause other conditions.
• Immunosuppressants slow the production of disease-fighting white blood cells. Side effects include an increased risk of infections. These medicines include azathioprine (Imuran, Azasan), mycophenolate (CellCept), rituximab (Rituxan, Riabni, others) and cyclophosphamide (Cytoxan). They also include methotrexate (Trexall, Xatmep, others), cyclosporine (Gengraf, Neoral, others), and tacrolimus (Astagraf XL, Envarsus XR, others). Newer medicines include eculizumab (Soliris), ravulizumab (Ultomiris) and efgartigimod (Vyvgart).

Depending on the type of paraneoplastic syndrome and symptoms, other medicines may include:

• Anti-seizure medicines, which may help control seizures associated with syndromes that cause electrical instability in the brain.
• Medicines to enhance nerve-to-muscle transmission. These medicines may improve symptoms of syndromes that affect muscle function. Some medicines enhance 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.

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Other medical treatments

Other treatments that may improve symptoms include:

• Plasmapheresis. This process separates the fluid part of the blood, called plasma, from your blood cells with a device known as a blood cell separator. The plasma, which contains the antibodies causing symptoms, is discarded and replaced with other fluids. Your red and white blood cells, along with your platelets, are returned to your body.
• Intravenous immunoglobulin (IVIg). Immunoglobulin contains healthy antibodies from blood donors. High doses of immunoglobulin speed up the destruction of the damaging antibodies in your blood.

If you have a paraneoplastic neurologic syndrome, it’s generally recommended that you don’t use certain cancer medicines called immune checkpoint inhibitors. These treatments activate the immune system to fight cancer. While this can help destroy the cancer, it also can lead to worsening of the immune attack on the nervous system.

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Other therapies

Other therapies may be helpful if a paraneoplastic syndrome has caused disability:

• Physical therapy. Specific exercises may help you regain some lost muscle function.
• Speech therapy. A speech therapist can help you relearn the necessary muscle control if you are having trouble speaking or swallowing.

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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 healthcare 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.

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Preparing for an appointment

Most people with paraneoplastic syndromes of the nervous system experience symptoms before being diagnosed with cancer.

Therefore, you’re likely to start by seeing your healthcare professional about your symptoms. You may be referred to a specialist in nervous system disorders, known as a neurologist, or a cancer specialist, known as an oncologist.

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What you can do

• Be aware of any pre-appointment restrictions. At the time you make the appointment, be sure to ask if there’s anything you need to do in advance, such as restrict your diet.
• Write down any symptoms you’re experiencing, including any that may seem unrelated to the reason for which you scheduled the appointment.
• Write down key personal information, including any major stresses or recent life changes.
• Make a list of all medicines, vitamins or supplements that you’re taking.
• Consider taking a family member or friend along. Sometimes it can be hard to remember all the information provided during an appointment. Someone who comes with you may remember something that you missed or forgot.
• Write down questions to ask your healthcare professional.
• Bring your images on a disc to hand to your healthcare professional at the appointment.

Your time with your healthcare professional may be limited. Preparing a list of questions can help you make the most of your time together. List your questions from most important to least important in case time runs out. Some basic questions to ask include:

• What’s the most likely cause of my symptoms?
• What diagnostic tests will you order? Do I need to prepare for these tests?
• Which specialists will I need to see?
• How soon am I likely to complete the tests and get results?
• What are you looking for in the tests?
• What conditions are you trying to rule out?

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What to expect from your doctor

Your healthcare professional may ask the following questions:

• Have you had any muscle weakness or lack of coordination?
• Have you had any different or involuntary muscle movements?
• Have you had any trouble with your vision?
• Do you have trouble chewing, swallowing or speaking?
• Do you have any trouble 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?
• Is it hard to perform everyday tasks with your hands?
• Have you had any numbness or tingling in your limbs?
• Have you had 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 your symptoms begin?
• Have your symptoms become worse?
• Have you been diagnosed with cancer?
• What medicines do you take, including medicines you take without a prescription and dietary supplements? What are the daily dosages?
• Have any close relatives had cancer? If so, what types of cancer?
• Have you ever smoked?
• Do you or does anyone in your family have some form of autoimmune disease?