Paraneoplastic neurological syndrome (PNS) is a group of rare disorders that develop as an indirect consequence of cancer. It is not caused by the tumor physically pressing on the nervous system, but by an abnormal immune response. The body’s immune system, when attacking a cancerous tumor, mistakenly targets and damages healthy cells in the brain, spinal cord, and peripheral nerves.
A defining feature of PNS is that neurological symptoms appear before the cancer is found in more than half of cases. This early onset presents an opportunity to detect an underlying malignancy at a more treatable stage.
How Cancer Triggers the Syndrome
Paraneoplastic neurological syndromes are triggered when a tumor expresses proteins, known as antigens, that are normally found only in the nervous system. The immune system recognizes these tumor antigens as foreign and produces antibodies and T-cells to destroy the cancer cells.
The problem arises from a phenomenon called cross-reactivity. The antibodies and T-cells created to fight the tumor cannot distinguish between the antigens on cancer cells and the very similar proteins on healthy nerve cells. This molecular mimicry leads the immune system to attack the patient’s nervous system, causing inflammation and damage.
Different types of cancer are associated with specific syndromes and corresponding onconeural antibodies. For example, small cell lung cancer, ovarian cancer, and breast cancer are frequently linked to certain types of PNS. The specific antibody identified can help point doctors toward the likely location of the underlying tumor.
Recognizing the Symptoms
The symptoms of paraneoplastic neurological syndrome are diverse and depend on which part of the nervous system is under attack. A characteristic is the rapid onset of these issues, often progressing over days to weeks, which suggests something other than a typical degenerative condition.
When the cerebellum is affected, a region of the brain that coordinates voluntary movements, individuals may experience problems with balance and walking (ataxia). They might also develop slurred speech (dysarthria), dizziness, and difficulties with fine motor skills, like buttoning a shirt. This collection of symptoms, called cerebellar degeneration, is a frequent manifestation of PNS.
If the immune response targets the cerebrum’s limbic system, which governs memory and emotion, symptoms can include profound memory loss, personality shifts, confusion, and seizures, a condition called limbic encephalitis. An attack on the spinal cord or peripheral nerves can lead to muscle weakness, loss of sensation, or numbness and tingling in the limbs, known as sensory neuropathy. In some cases, it can cause severe muscle stiffness and spasms, a condition called stiff-person syndrome.
Damage to the brainstem and its cranial nerves can result in vision changes, including double vision or uncontrolled eye movements. Difficulty swallowing (dysphagia) is another potential symptom, as are changes in hearing.
How Paraneoplastic Neurological Syndrome Is Diagnosed
The first step in diagnosis is a thorough neurological exam to assess reflexes, muscle strength, coordination, sensation, memory, and cognitive function. A primary component of the diagnostic process is blood testing to search for specific onconeural antibodies. The presence of these antibodies, rarely found in people without PNS, provides strong evidence that the neurological symptoms are caused by an autoimmune response to an underlying cancer.
Finding a specific antibody can help narrow the search for the associated tumor type. A spinal tap, or lumbar puncture, is another diagnostic tool. In this procedure, a small sample of cerebrospinal fluid (CSF) is collected and analyzed for signs of inflammation or onconeural antibodies not detectable in the blood.
Once PNS is suspected, the focus shifts to finding the hidden tumor. Magnetic Resonance Imaging (MRI) of the brain and spinal cord can reveal areas of inflammation or rule out other causes. To locate the primary cancer, doctors use whole-body imaging techniques like Positron Emission Tomography (PET) and Computed Tomography (CT) scans.
Treating the Syndrome and the Underlying Cancer
Treatment for PNS is a two-part strategy: treating the underlying cancer and suppressing the immune system’s attack on the nervous system. The primary goal is to control the tumor with standard cancer therapies such as surgery, chemotherapy, or radiation therapy. Effectively treating the cancer removes the source of the antigens stimulating the immune response, which can lead to stabilization of neurological symptoms.
At the same time, treatments are administered to calm the autoimmune attack. Corticosteroids like prednisone are used to reduce inflammation, while other therapies aim to remove or neutralize harmful antibodies. These include plasmapheresis, a process that filters antibodies out of blood plasma, and intravenous immunoglobulin (IVIg). In some cases, stronger immunosuppressant drugs may be used to slow the production of immune cells.
Outlook and Long-Term Management
The prognosis for an individual with paraneoplastic neurological syndrome is highly variable. It depends on the type of underlying cancer, the specific onconeural antibody involved, and the extent of neurological damage before treatment begins. Prompt diagnosis and treatment of both the cancer and the syndrome are associated with better outcomes.
Some patients experience significant recovery of neurological function once the tumor is treated and the autoimmune response is controlled. For others, the damage to the nervous system can be permanent, leading to long-term disability. Syndromes affecting the central nervous system, like cerebellar degeneration, often have a poorer recovery prognosis compared to those affecting the peripheral nerves.
Long-term management and rehabilitation are often necessary. Physical therapy can help patients improve balance, strength, and coordination. Occupational therapy assists individuals in adapting to lasting deficits and finding new ways to perform daily activities. Speech therapy can provide strategies for those with speech or swallowing difficulties.