The influence of cancer on the nervous system extends far beyond the physical location of the primary tumor. The nervous system is a complex network composed of the central nervous system (CNS)—the brain and spinal cord—and the peripheral nervous system (PNS)—the nerves outside the CNS. Cancer can affect this network through multiple pathways, ranging from direct mechanical damage caused by tumor growth to distant, immune-mediated attacks and unintended consequences of therapeutic interventions. Understanding this intricate interaction is necessary to comprehend the diverse range of neurological symptoms experienced by patients. Both the malignancy itself and the necessary treatments introduce distinct mechanisms of neural damage.
Direct Structural Impact of Tumors
The most straightforward way cancer affects the nervous system is through the physical presence of a tumor mass, causing destruction and displacement of delicate neural tissue. Primary brain tumors (e.g., gliomas) and metastatic tumors (often from lung, breast, or melanoma cancers) occupy space within the rigid confines of the skull or spinal column. This growth leads to “mass effect,” where the tumor compresses adjacent functional brain regions, causing specific symptoms. For example, a tumor in the motor cortex may cause weakness on one side of the body, while one in the occipital lobe can lead to vision problems.
Tumor growth can also obstruct the normal flow of cerebrospinal fluid (CSF), the liquid that bathes the brain and spinal cord. This obstruction results in a buildup of fluid and increased intracranial pressure. The elevated pressure causes global symptoms like persistent headaches, nausea, vomiting, and altered consciousness. Furthermore, cancer cells can directly infiltrate and destroy local neural tissue, disrupting the circuitry required for normal function.
When cancer spreads to the spine, it often involves the vertebral bones, leading to spinal cord compression. This compression may be caused by the tumor mass or by bone fragments from a pathological fracture of a weakened vertebra. Symptoms of spinal cord compression, such as myelopathy, include weakness, numbness, or loss of sensation below a specific level, along with changes in bladder and bowel function. Tumors growing near nerve plexuses, like the brachial plexus, can also directly compress or invade nerve bundles. This results in severe pain, sensory loss, and muscle weakness in the corresponding limb.
Indirect Effects: Paraneoplastic Syndromes
Paraneoplastic neurological syndromes (PNS) are distant effects of cancer not caused by a physical tumor mass or metastasis. These syndromes involve an abnormal immune response where the body mistakenly attacks healthy parts of the nervous system. The core mechanism is antigenic mimicry: cancer cells (often from small cell lung or ovarian cancer) express antigens that are also present on nerve cells. The immune system attacks the tumor antigens using autoantibodies and cytotoxic T-cells, causing nerve cells to become “collateral damage.”
The resulting neurological damage can affect any part of the nervous system, leading to distinct syndromes. Paraneoplastic cerebellar degeneration (PCD), for instance, causes severe, progressive loss of coordination and balance due to the destruction of Purkinje cells in the cerebellum. Another example is limbic encephalitis, where inflammation of the brain’s limbic system causes short-term memory loss, seizures, and personality changes. These neurological symptoms often appear months before the underlying cancer is detected, sometimes providing the first clue to malignancy.
Lambert-Eaton Myasthenic Syndrome (LEMS) is a PNS that impairs communication between nerves and muscles, typically causing weakness in the hips and shoulders. LEMS is frequently associated with small cell lung cancer and is caused by autoantibodies targeting voltage-gated calcium channels on nerve endings. The severity of PNS symptoms does not correlate with the size or stage of the tumor; even a small, hidden tumor can provoke a devastating immune attack. Treatment involves addressing the underlying tumor and suppressing the immune response to halt progressive neural destruction.
Treatment-Related Neurotoxicity
Treatments designed to eradicate cancer can cause unintended damage to the nervous system, known as neurotoxicity. Chemotherapy-Induced Peripheral Neuropathy (CIPN) is a common and limiting side effect, affecting peripheral nerves. CIPN causes symptoms like numbness, tingling, or burning pain, typically in a “glove-and-stocking” distribution in the hands and feet. Platinum agents like oxaliplatin and cisplatin are known to cause CIPN by damaging mitochondria and ion channels in sensory neurons.
Taxanes, such as paclitaxel, also cause CIPN by disrupting microtubules within nerve axons, which are necessary for transporting cellular materials down the long nerve fibers. The damage caused by these drugs often leads to dose-dependent toxicity, meaning the risk and severity increase with the total amount of drug administered. Symptoms may worsen after treatment ends, a phenomenon called “coasting,” and can persist for months or years, significantly impacting quality of life.
Radiation therapy uses high-energy beams to destroy cancer cells but can also damage healthy neural tissue. Effects are categorized by onset: acute effects occur within days, while late delayed effects appear months or years later. A serious late effect is radiation necrosis, the death of brain tissue caused by damage to small blood vessels and subsequent lack of oxygen. Radiation to the spinal cord can lead to myelopathy, causing progressive weakness and sensory loss.
Surgical intervention for tumors near or within the brain and spinal cord carries the risk of direct mechanical injury to nerves. Surgeons aim for maximal safe resection, but manipulating and removing a mass near delicate tracts can result in traumatic or ischemic injury. The proximity of a tumor to functional neural pathways means that a degree of localized neurological deficit may be an unavoidable consequence of successful tumor removal.