Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in adults, arising from supportive glial cells. Seizures are a frequent and significant symptom, often serving as the first noticeable sign prompting medical evaluation. The physical and sensory manifestations vary widely depending on the tumor’s location and size. Understanding glioblastoma seizures requires examining the biological mechanisms that trigger them and recognizing their distinct presentations.
Understanding the Link Between Tumors and Seizures
The presence of a glioblastoma creates an unstable environment in the surrounding brain tissue, lowering the threshold for electrical activity that causes a seizure. The tumor, along with associated peritumoral edema or swelling, exerts a physical mass effect that irritates nearby healthy neurons. This mechanical pressure contributes to the brain’s hyperexcitable state. Seizures are common in GBM patients, with an estimated 40% to 70% experiencing at least one seizure during the course of their disease.
Tumor cells’ chemical activity is a powerful mechanism. Glioblastoma cells release excessive amounts of the excitatory neurotransmitter glutamate into the extracellular space. This accumulation over-stimulates adjacent healthy neurons, leading to excitotoxicity and increasing the likelihood of uncontrolled electrical discharge. The tumor’s aggressive infiltration into the surrounding cortex further disrupts the normal inhibitory and excitatory balance of neural networks.
This process of tumor-induced epileptogenesis primarily occurs in the brain tissue immediately bordering the tumor mass. The tumor also alters the local blood-brain barrier, which can contribute to the inflammatory environment that promotes neuronal hyperexcitability. This combination of physical irritation, chemical imbalance, and inflammation makes the brain susceptible to the sudden, synchronized electrical bursts that constitute a seizure.
Recognizing the Different Types of Glioblastoma Seizures
Glioblastoma seizures are most frequently classified as focal onset, originating in a specific, localized area of one brain hemisphere. The symptoms observed directly reflect the function of the brain region where the tumor is situated. Focal awareness seizures occur when the patient remains fully conscious and aware throughout the event.
Focal awareness seizures can manifest as sudden, involuntary jerking or twitching of a single limb if the tumor is near the motor cortex. A patient might experience a brief, intense sensory phenomenon, such as an unpleasant smell (phantosmia) or an unusual taste (gustatory hallucination), pointing toward irritation in the temporal lobe. Other manifestations include transient visual disturbances or flashes of light if the tumor is located near the occipital lobe.
The focal impaired awareness seizure is another common presentation, where the patient’s consciousness is altered, preventing interaction with their environment. During these events, the person may stare blankly or engage in repetitive, non-purposeful behaviors like fumbling with clothes, lip-smacking, or wandering aimlessly. The patient typically has no memory of the event afterward. The duration is usually short, lasting from 30 seconds to a few minutes.
Less commonly, a focal seizure can spread rapidly to involve both sides of the brain, resulting in a focal-to-bilateral tonic-clonic seizure. This type involves initial stiffening (tonic phase) followed by rhythmic jerking (clonic phase) of the limbs and trunk, accompanied by loss of consciousness. These generalized convulsions are serious medical events requiring immediate attention. They can result in post-seizure confusion or temporary weakness known as Todd’s paresis.
Treatment Approaches for Glioblastoma Seizure Control
Management of glioblastoma-related seizures relies primarily on antiepileptic drugs (AEDs) to stabilize neuronal activity in the peritumoral tissue. Selecting an appropriate AED is complicated by the need for concurrent brain tumor treatments, such as chemotherapy with Temozolomide. Older AEDs, like phenytoin or carbamazepine, are enzyme-inducing drugs that accelerate the metabolism of other medications, potentially reducing chemotherapy effectiveness.
Newer generation AEDs that do not significantly interact with the liver’s enzyme systems are preferred. Levetiracetam is often the first-line choice because it lacks problematic drug-to-drug interactions, ensuring the patient receives the full therapeutic benefit of cancer treatments. Valproic acid is another option, but as an enzyme inhibitor, it requires close monitoring of chemotherapy drug levels.
Beyond medication, surgical tumor resection plays a significant role in seizure control. Removing the bulk of the tumor and the surrounding irritative tissue often leads to a reduction in seizure frequency and severity, sometimes achieving complete seizure freedom.
AEDs are necessary for individuals who have experienced a seizure. Current guidelines recommend against the routine use of AEDs in patients who have not yet had a seizure, as prophylactic use has not been shown to be effective. For the severe, prolonged event known as status epilepticus, emergency medication is administered to quickly stop the continuous seizure activity.