Paraneoplastic Syndromes of the Nervous System

Diagnosis

Diagnosing paraneoplastic syndrome of the nervous system usually involves a physical exam, blood tests and imaging studies. A spinal tap may also be needed to evaluate the fluid surrounding the brain and spinal cord. Because these syndromes are linked with cancer, age-appropriate cancer screening tests are often part of the evaluation.

A clinical exam is typically the first step. A neurologist or healthcare professional assesses symptoms through simple in-office tests. These tests help evaluate reflexes, muscle strength, muscle tone, coordination, balance, vision, hearing, sense of touch, memory and mood. The results help guide which additional tests are needed.

Laboratory tests may include blood work to check for antibodies linked to paraneoplastic syndromes of the nervous system. Some tests may help rule out infections, hormone disorders or metabolic conditions. A spinal tap may be done to collect cerebrospinal fluid for analysis. This fluid can show antibodies that might not appear in blood samples. Finding the same antibodies in both samples strengthens the likelihood of a paraneoplastic cause.

Imaging tests are used to look for tumors or other causes of symptoms. These may include CT scans that create cross-sectional images of tissues, MRI scans that provide detailed 3D images and PET scans that use radioactive tracers to show metabolic activity. A combined PET-CT scan may be used to detect small cancers that are common in people with paraneoplastic neurological disorders. If imaging does not find a tumor, the immune system may be keeping it very small. Follow-up imaging every few months is often recommended until a cause becomes clear.

Treatment

Treatment focuses on managing the underlying cancer and calming the immune response that is affecting the nervous system. The specific approach depends on the type of paraneoplastic syndrome and the symptoms it causes. Treatment often combines cancer therapies, medicines that reduce immune-related damage and supportive therapies.

Medications used in treatment may include corticosteroids to reduce inflammation. These medicines can help the immune system stop attacking the nervous system but may cause long-term side effects such as high blood pressure, high cholesterol, weakened bones or type 2 diabetes. Immunosuppressants may also be prescribed to slow the production of certain white blood cells. These medicines can increase the risk of infection. Options include azathioprine, mycophenolate, rituximab, cyclophosphamide, methotrexate, cyclosporine, tacrolimus and newer agents such as eculizumab, ravulizumab and efgartigimod. Additional medicines may be used depending on symptoms, such as anti-seizure medicines or medicines that improve nerve-to-muscle communication, including pyridostigmine.

Other medical treatments focus on reducing the harmful antibodies that contribute to symptoms. Plasmapheresis removes the antibody-containing plasma and replaces it with other fluids while returning the blood cells to the body. Intravenous immunoglobulin introduces healthy antibodies from donors to help reduce the impact of damaging antibodies. For most people with paraneoplastic neurologic syndromes, immune checkpoint inhibitors are not recommended because they can worsen immune attacks on the nervous system.

Other therapies may support recovery and help manage long-term effects. Physical therapy can improve strength and mobility if muscle function has been affected. Speech therapy may help with speaking or swallowing challenges. These therapies can improve daily function and help maintain independence as treatment progresses.