A seizure is a sudden, uncontrolled surge of electrical activity within the brain that causes temporary changes in movement, behavior, or consciousness. When a patient experiences a seizure, especially a generalized one, subsequent blood tests may reveal an elevation in certain substances known as liver enzymes. Elevated liver enzymes signal that liver cells are damaged or stressed, releasing their contents into the bloodstream. This connection often presents a confusing clinical picture, as the cause of the enzyme spike must be carefully investigated. The elevation may stem directly from the physical event of the seizure or, more commonly, be a side effect of the medication used for treatment.
What Liver Enzymes Are and Why They Are Measured
Liver enzymes are proteins that help speed up chemical reactions necessary for the liver’s functions, such as metabolism and detoxification. The most commonly measured enzymes are alanine aminotransferase (ALT) and aspartate aminotransferase (AST). These enzymes are normally housed inside liver cells (hepatocytes) but are also present in other tissues like muscle.
When liver cells are injured, these enzymes leak out and enter the bloodstream, causing their concentration in the blood to rise. A significant increase in ALT and AST levels is a reliable sign of damage to the liver cells. While ALT is considered more specific to the liver, AST is also found in heart and skeletal muscle, which is an important distinction. Other markers, such as alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT), are also checked, as their elevation may suggest problems with the bile ducts rather than the liver cells themselves.
Seizure Activity’s Direct Effect on Liver Function
The physical act of a generalized convulsive seizure can directly lead to a temporary elevation of liver enzymes. One mechanism involves the intense muscle contractions that occur during a tonic-clonic seizure, which can induce rhabdomyolysis—the breakdown of skeletal muscle tissue. Rhabdomyolysis releases intracellular muscle contents, including the enzyme creatine kinase (CK), into the circulation.
Since AST is highly concentrated in muscle tissue, this muscle breakdown causes a noticeable rise in serum AST levels. This AST elevation is often accompanied by a very high CK level, which helps physicians distinguish a muscle-related enzyme spike from a liver-related one. These elevations are usually transient, peaking a day or two after the seizure and then returning to normal levels.
Another factor is oxygen deprivation, or hypoxia, especially in prolonged seizure events known as status epilepticus. A lengthy seizure can decrease the oxygen supply to the liver, leading to ischemic stress on the hepatocytes. This lack of oxygen can damage liver cells, causing them to release ALT and AST into the bloodstream. This type of liver stress is seen in severe seizures and is considered an acute, stress-induced injury.
Medication-Related Liver Enzyme Elevation
The most frequent cause of elevated liver enzymes in patients with seizures is the use of Anti-Epileptic Drugs (AEDs). Many AEDs are metabolized by the liver, making them a common source of drug-induced liver injury (DILI). DILI can manifest in two distinct patterns: predictable toxicity and rare, idiosyncratic reactions.
Dose-related toxicity occurs because some AEDs, such as carbamazepine, induce the liver’s drug-metabolizing enzymes. This process can cause mild, chronic elevations of ALT and AST, often without causing true liver damage. These mild elevations typically do not require the drug to be stopped, but they signal that the liver is working harder to process the medication.
Idiosyncratic reactions are rare, unpredictable, and can be severely damaging, often leading to acute liver failure. Examples of AEDs historically associated with a higher risk of severe hepatotoxicity include valproate, phenytoin, and carbamazepine. Valproate, for instance, is known for its potential to cause liver failure, particularly in young children and those on multiple seizure medications.
These reactions can present as hepatocellular injury, characterized by very high ALT and AST levels, or cholestatic injury, marked by elevated ALP and bilirubin, indicating a problem with bile flow. Phenytoin, carbamazepine, and lamotrigine are also known to cause a severe, immune-mediated reaction called Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), which can include acute, severe liver injury.
How Doctors Determine the Cause and What Comes Next
When a patient’s blood test shows elevated liver enzymes, physicians must differentiate between the direct seizure effect, the drug effect, and other unrelated causes like viral hepatitis or fatty liver disease. The timing of the enzyme elevation is a major diagnostic clue. An elevation immediately after a seizure suggests rhabdomyolysis or hypoxia, while an elevation appearing weeks to months after starting a new AED points toward DILI.
The pattern and magnitude of the enzyme levels are also informative. If AST is significantly higher than ALT, and Creatine Kinase (CK) is very high, the cause is likely muscle injury from the seizure. If ALT and AST are extremely elevated, often into the hundreds or thousands, it suggests acute hepatocellular damage, possibly from an idiosyncratic drug reaction. Checking true liver function markers, such as bilirubin and the international normalized ratio (INR), helps determine the severity, as a rise suggests serious impairment of the liver’s ability to function.
Routine monitoring of liver enzymes is standard practice when a patient begins a new AED or has a dose change, allowing doctors to detect potential problems early. For mild, transient elevations linked to the physical seizure itself, the physician may choose to observe the patient and repeat the blood work. If the enzymes are severely elevated, continue to rise, or if the patient shows signs of liver failure, the medication will likely need to be stopped immediately and replaced with an alternative treatment.