Chemotherapy treats many cancers by targeting rapidly dividing cells. While designed to combat cancer, these treatments can cause various side effects throughout the body. Neurological complications, including seizures, can sometimes arise. This article explores the relationship between chemotherapy and seizures and how they can manifest during cancer treatment.
Chemotherapy Drugs That Directly Affect the Brain
Some chemotherapy agents directly impact the central nervous system, leading to neurotoxic effects that can manifest as seizures.
Methotrexate
Methotrexate, for example, can cause neurotoxicity after intravenous or intrathecal administration, potentially by disrupting folate homeostasis or causing direct neuronal damage. It can lead to stroke-like symptoms, encephalopathy, and seizures, often 2 to 14 days post-administration.
Ifosfamide
Ifosfamide can induce encephalopathy in up to 30% of patients, including seizures. The neurotoxicity is often linked to the formation of chloroacetaldehyde (CAA), which can cross the blood-brain barrier and cause neurotoxic effects. This encephalopathy is reversible upon stopping the infusion.
Cytarabine
High doses of cytarabine are associated with central nervous system dysfunction, including seizures, though less common than cerebellar syndrome. While the exact mechanism remains unclear, post-mortem examinations have shown loss of Purkinje cells in the cerebellum. Renal impairment can increase the risk of neurotoxicity due to reduced drug clearance.
Fluorouracil (5-FU)
Fluorouracil (5-FU) can also induce neurotoxicity, including seizures, though rare. One proposed mechanism involves the blockade of the Krebs cycle by catabolites of 5-FU, which reduces ATP production. Another theory suggests that 5-FU can lead to thiamine deficiency or that DPD enzyme deficiency, which metabolizes 5-FU, can cause drug accumulation and neurotoxic effects.
Cisplatin
Cisplatin primarily causes peripheral neuropathy but can occasionally induce encephalopathy and seizures. The precise mechanism for its central nervous system effects is not fully understood, but heavy metal toxicity or demyelination have been proposed. Seizures associated with cisplatin are rare without other contributing factors like brain pathology or electrolyte imbalances.
Vincristine
Vincristine is known for its neurotoxicity, which can include seizures, though central nervous system involvement is less common than peripheral neuropathy. The mechanism is not entirely clear, but it may involve direct neurotoxic effects or the induction of SIADH, leading to hyponatremia, which can lower the seizure threshold. Neurotoxicity from vincristine is dose-dependent and cumulative.
Other Factors That Can Lead to Seizures
Beyond the direct neurotoxic effects of specific chemotherapy drugs, several other conditions associated with cancer or its treatment can contribute to seizures. Metabolic and electrolyte imbalances are common, as chemotherapy can cause disruptions like hyponatremia (low sodium) or hypocalcemia (low calcium). These imbalances can alter neuronal excitability and lower the brain’s seizure threshold. These disturbances often arise from treatment side effects or the underlying cancer.
Infections
Infections, particularly central nervous system infections, are another significant factor. Chemotherapy often immunocompromises cancer patients, making them vulnerable to bacterial, viral, or fungal infections that can affect the brain and trigger seizures. These infections can cause inflammation, swelling, or direct damage to brain tissue, precipitating seizure activity.
Brain Metastases
Brain metastases, or the spread of cancer to the brain, are a frequent cause of seizures in cancer patients. A primary brain tumor can also directly irritate brain tissue, leading to seizures. These lesions can disrupt normal brain function, increase intracranial pressure, or cause localized irritation, leading to seizure development.
Non-Chemotherapy Medications
Certain non-chemotherapy medications can interact with chemotherapy or independently lower the seizure threshold. For example, some antibiotics or antidepressants commonly used in cancer patients have been linked to seizures. These drug interactions or medication side effects can complicate a patient’s neurological profile during cancer treatment.
Organ Dysfunction
Organ dysfunction, such as impaired kidney or liver function, can also play a role in seizure development. These organs metabolize and clear drugs, and impaired function can lead to the accumulation of chemotherapy agents or their toxic metabolites. This increased concentration of neurotoxic substances can contribute to neurological complications, including seizures.
Recognizing and Managing Seizures
Recognizing seizure signs is important for prompt intervention and patient safety. Seizures can manifest in various ways, from subtle changes in awareness like staring spells, to more overt physical symptoms. Generalized tonic-clonic seizures, for instance, involve loss of consciousness, body stiffening (tonic phase), followed by rhythmic jerking movements of the limbs (clonic phase). Other symptoms include confusion, unresponsiveness, repetitive movements, or a sudden fall.
If a seizure occurs, immediate medical attention is necessary. During a seizure, ensuring the person’s safety is paramount. This involves moving them away from hazards, cushioning their head, and loosening any tight clothing around the neck. Note the time the seizure began and how long it lasts, as this information is useful for medical professionals. Do not attempt to restrain the person or place anything in their mouth during a seizure.
Diagnosis involves a neurological examination and review of the patient’s medical history, including current medications and cancer status. Diagnostic tests may include an electroencephalogram (EEG) to record brain electrical activity and identify abnormal patterns associated with seizures. Imaging scans like magnetic resonance imaging (MRI) of the brain are often performed to check for brain tumors, metastases, or other structural abnormalities causing seizures.
Management strategies for chemotherapy-induced seizures involve addressing the underlying cause. If a specific chemotherapy drug is implicated, adjusting its dosage or switching to an alternative agent may be considered. Anti-seizure medications are prescribed to control and prevent further seizures, with choices depending on the seizure type and potential interactions with other cancer treatments. Additionally, any identified metabolic imbalances or infections are treated concurrently to stabilize the patient’s condition.