Paraneoplastic Neurological Syndrome

Paraneoplastic neurological syndromes are rare conditions that occur when the body’s immune system, while fighting cancer, mistakenly attacks the nervous system, causing symptoms that often appear before the cancer itself is even discovered.

Table of contents

• What Is Paraneoplastic Neurological Syndrome?
• Symptoms and How They Develop
• Types of Paraneoplastic Syndromes
• What Causes These Syndromes
• How the Condition Is Diagnosed
• Treatment Options
• Living with Paraneoplastic Neurological Syndrome

What Is Paraneoplastic Neurological Syndrome?

Paraneoplastic neurological syndromes are a group of rare disorders that develop in some people who have cancer. These conditions affect the nervous system, but they are not caused by the cancer spreading directly to the brain, spinal cord, or nerves. Instead, they happen when the body’s immune system fights the cancer but also attacks healthy parts of the nervous system by mistake.^[1]

The word paraneoplastic means “related to cancer but not caused by the cancer itself.” These syndromes can affect the brain, spinal cord, peripheral nerves (the nerves throughout your body), or muscles. In addition to the nervous system, paraneoplastic syndromes can also affect other parts of the body including hormones, skin, blood, and joints.^[1]

These disorders are uncommon. Experts estimate that about 8 out of every 100 people with cancer develop a paraneoplastic syndrome.^[5] Although rare, recognizing these syndromes is important because they often appear before a person knows they have cancer. The symptoms can be the first sign that leads doctors to discover a hidden tumor.^[2]

Symptoms and How They Develop

Symptoms of paraneoplastic neurological syndromes usually develop quickly, often over days to weeks. They frequently begin even before cancer is diagnosed, which can make them confusing and frightening for patients.^[1]

The symptoms vary widely depending on which part of the nervous system is affected. Common symptoms include:^[1]

• Trouble walking
• Problems with balance
• Loss of muscle coordination
• Muscle weakness or loss of muscle tone
• Difficulty with fine motor skills, such as picking up small objects
• Trouble swallowing
• Slurred speech or stuttering
• Memory loss and other thinking problems
• Vision changes
• Trouble sleeping
• Seizures
• Hallucinations
• Movements that cannot be controlled

Some people may experience symptoms that are specific to the nervous system, such as double vision, confusion, or difficulty coordinating muscles.^[3] These symptoms can be wide-ranging and may involve multiple parts of the nervous system at once.^[3]

Types of Paraneoplastic Syndromes

There are several different types of paraneoplastic syndromes that affect the nervous system. Each type affects a different part of the nervous system and causes different symptoms.^[1]

Cerebellar degeneration, also called cerebellar ataxia, happens when nerve cells are lost in the cerebellum, the part of the brain that controls muscle function and balance. People with this condition may have trouble walking, lack of coordination in the arms and legs, difficulty maintaining posture, and dizziness. They may also experience nausea, uncontrolled eye movements, double vision, trouble speaking, or difficulty swallowing.^[1]

Limbic encephalitis involves swelling and inflammation of the limbic system, which controls emotions, behaviors, and certain memory functions. This can cause personality changes, mood changes, memory loss, seizures, hallucinations, or drowsiness.^[1]

Encephalomyelitis refers to inflammation of both the brain and spinal cord. Symptoms vary widely depending on which areas are affected.^[1]

Other types include opsoclonus-myoclonus, which causes rapid, irregular eye movements and muscle jerks; stiff person syndrome, which leads to severe muscle stiffness that worsens over time; and myelopathy, which involves injury to the spinal cord causing changes in bowel and bladder function, weakness, and numbness.^[1]

Lambert-Eaton myasthenic syndrome is caused by disrupted communication between nerves and muscles. It typically causes muscle weakness in the pelvis and legs, fatigue, trouble swallowing and speaking, irregular eye movement, double vision, dry mouth, and erectile dysfunction. When it occurs as a paraneoplastic syndrome, it is typically associated with lung cancer.^[1]

Myasthenia gravis also involves disrupted communication between nerves and muscles, causing weakness and rapid fatigue of muscles under voluntary control, including those in the face, eyes, arms, legs, and muscles involved in chewing, swallowing, talking, and breathing.^[1]

Additional conditions include dysautonomia (affecting the autonomic nervous system), neuromyotonia, peripheral neuropathy (affecting nerves throughout the body), muscle weakness, and psychiatric abnormalities such as hallucinations, depression, paranoia, or anxiety.^[3]

What Causes These Syndromes

Paraneoplastic neurological syndromes occur when cancer-fighting agents of the immune system also attack parts of the nervous system. The body develops an immune response to fight the cancer, but this response misfires and damages healthy nervous system tissue.^[1]

When tumor cells are present, they can express certain proteins that normally exist in the nervous system. The immune system recognizes these proteins as foreign and creates antibodies (proteins that help fight infections) to attack the tumor. However, these antibodies can also attack normal nerve cells that have similar proteins on their surface. This is called an autoimmune response—when the body’s defense system attacks its own healthy tissues.^[5]

Sometimes, tumors release hormones or other substances that cause organs to work improperly, even without the tumor spreading.^[5] The symptoms are not caused by the cancer directly invading the nervous system or by the spread of cancer to other areas. They are caused by this mistaken immune attack.^[2]

The tumors most commonly associated with paraneoplastic neurological syndromes include small-cell lung cancer, ovarian cancer, breast cancer, and tumors that contain nervous tissue such as teratomas (tumors made of different types of tissue).^[6]

How the Condition Is Diagnosed

Diagnosing paraneoplastic neurological syndrome requires several types of tests and examinations. Because paraneoplastic syndromes are associated with cancer, doctors may also need to perform cancer screening tests.^[8]

The doctor will first perform a physical examination and a neurological exam. During this exam, the doctor asks questions and performs simple tests to check reflexes, muscle strength, muscle tone, sense of touch, vision, hearing, coordination, balance, mood, and memory.^[8]

Blood tests are an important part of diagnosis. Doctors look for specific antibodies commonly associated with paraneoplastic syndromes. These are called onconeural antibodies or paraneoplastic antibodies. The presence of these antibodies can help confirm the diagnosis and can sometimes suggest which type of cancer might be present.^[2] However, it is important to know that in 30 to 40 percent of cases, paraneoplastic syndromes can occur without these antibodies being detectable.^[2]

A spinal tap, also called a lumbar puncture, may be performed. During this procedure, a doctor inserts a needle into the lower spine to remove a small amount of cerebrospinal fluid (the fluid that cushions the brain and spinal cord). Sometimes paraneoplastic antibodies are found in cerebrospinal fluid even when they cannot be seen in the blood. Finding antibodies in both cerebrospinal fluid and blood provides strong evidence of a paraneoplastic syndrome.^[8]

Imaging tests help doctors find tumors or other causes of symptoms. These may include computerized tomography (CT) scans, magnetic resonance imaging (MRI), positron emission tomography (PET) scans, or other types of scans.^[8] If conventional screening for cancer is negative, a PET scan combined with a CT scan can be particularly useful for finding hidden cancers.^[2]

The initial test for identifying paraneoplastic neurological disorders is usually a blood test that attempts to identify the characteristic antibody. When found, certain antibodies can help focus the search for specific cancers.^[3] If cancer is not detected initially, patients need follow-up surveillance because the cancer may develop later.^[2]

Treatment Options

Treatment for paraneoplastic neurological syndromes involves several approaches. The most effective step is identifying and treating the underlying cancer. Cancer detection and treatment are crucial components of managing these syndromes.^[2]

Treatment directed toward the cancer itself—such as surgery, radiation therapy, or chemotherapy—can sometimes help reverse the injury to the nervous system. In some cases, treating the cancer and using other therapies may prevent further damage and improve symptoms and quality of life. However, sometimes paraneoplastic syndromes can result in permanent damage to the nervous system.^[1]

Immunotherapy is another important treatment approach. Because paraneoplastic syndromes are caused by an autoimmune response, treatments that suppress or modify the immune system can be helpful. Immunotherapy includes steroids, intravenous immunoglobulin (IVIgG), plasmapheresis (a procedure that filters the blood to remove antibodies), cytotoxic medications, and rituximab (a drug that targets certain immune cells).^[2]

Immunotherapy is particularly effective in paraneoplastic syndromes associated with antibodies that target proteins on the surface of nerve cells, such as those involving voltage-gated potassium channel complex, NMDA receptor antibodies, and voltage-gated calcium channel antibodies.^[2]

Previously, paraneoplastic syndromes were thought to respond poorly to treatment. However, it is now recognized that there is a subgroup of these syndromes, mostly those associated with antibodies to antigens on the neuronal cell surface, that are highly responsive to treatment.^[4]

Supportive therapy is also an important part of treatment. This includes symptomatic treatment with medications for seizures or pain, as well as physical therapy, speech therapy, and occupational therapy to help maintain function and independence.^[2]

Living with Paraneoplastic Neurological Syndrome

Living with a paraneoplastic neurological disorder can be challenging. The condition affects not only physical abilities but also emotional well-being. Depression is very common for people with these syndromes and may even be a direct effect of the disorder itself.^[12]

Support is essential. Connecting with others who are experiencing similar challenges can be helpful. Discussing feelings with family and friends and seeking help from doctors for depression or other emotional difficulties is important.^[12]

An occupational therapist can help people figure out how to stay as independent as possible using tools and equipment adapted to various disabilities. This might include special eating utensils, dressing aids, bathroom safety equipment, or mobility devices.^[12]

For people with speech difficulties, assisted communication devices can help maintain the ability to communicate with others. These devices range from simple to complex, depending on individual needs.^[12]

Staying as active and fit as possible is important for both physical and mental health. Evidence from people who have lived with paraneoplastic syndromes for a long time suggests that regular exercise and activity can lead to greater independence and better control over neurological symptoms. Working with a physical therapist is ideal, but even doing as much as is safely possible can make a difference.^[12]

Systematic support that includes psychological help and rehabilitation interventions can be beneficial for managing the complex challenges of living with these conditions.^[11]