Epilepsy has no single cause. It can result from genetic mutations, brain injuries, infections, strokes, immune system problems, and metabolic disorders. Yet despite decades of research, the cause remains unknown in roughly 50% of cases worldwide. Understanding the known causes helps clarify why seizures happen and, in many cases, how they can be managed.
How Seizures Start in the Brain
Every seizure begins with a disruption in the brain’s electrical signaling. Normally, your brain cells communicate through a careful balance of excitatory and inhibitory signals. The excitatory signals tell neurons to fire, while the inhibitory signals tell them to quiet down. In epilepsy, this balance tips toward too much excitation, too little inhibition, or both. The result is a burst of uncontrolled electrical activity that spreads through part or all of the brain.
This imbalance often involves two key chemical messengers. Glutamate drives neurons to fire, and GABA tells them to stop. When glutamate levels run too high or GABA levels drop too low, the brain becomes prone to seizures. Different causes of epilepsy disrupt this balance through different pathways, but the end result is the same: neurons firing when they shouldn’t be.
Genetic Causes
Some forms of epilepsy run in families, caused by mutations in genes that control how brain cells send electrical signals. The most well-studied mutations affect genes responsible for sodium channels, tiny gateways on the surface of neurons that regulate electrical impulses. When these channels don’t work properly, the brain’s inhibitory neurons can’t do their job effectively, leaving the brain vulnerable to runaway electrical activity.
More than 600 mutations have been identified in just one of these genes, called SCN1A. Different types of mutations in this gene cause different levels of severity. Mild mutations that subtly alter channel function tend to cause a condition where children develop febrile seizures (seizures triggered by fever) that may continue into adulthood. More severe mutations that completely knock out the gene’s function cause Dravet syndrome, a serious form of childhood epilepsy that resists treatment. In both cases, research in animal models shows the core problem is the same: the brain’s inhibitory circuits can’t keep up, so seizures break through.
Genetic epilepsy doesn’t always mean a parent passed it down. Many mutations occur spontaneously during early development and aren’t present in either parent’s DNA. The genetic category also includes complex patterns where multiple genes each contribute a small amount of risk, making it harder to pinpoint a single cause.
Structural Brain Abnormalities
Physical changes to the brain’s structure are one of the most identifiable causes of epilepsy. These can be present from birth or develop later in life. In children, the most common structural cause is focal cortical dysplasia, a condition where a small patch of brain tissue didn’t develop normally before birth. The neurons in that area are disorganized, and they tend to generate abnormal electrical signals. Focal cortical dysplasia is responsible for nearly half of drug-resistant epilepsy cases in both children and adults, though it often responds well to surgical treatment when medications fail.
Other structural causes include brain tumors (both cancerous and benign), blood vessel malformations, and scarring from previous injuries. These abnormalities irritate surrounding brain tissue, creating a focus point where seizures originate. MRI scans can often identify these structural problems, which is why brain imaging is a standard part of an epilepsy workup.
Traumatic Brain Injury
A head injury can trigger epilepsy weeks, months, or even years after the initial trauma. This is called post-traumatic epilepsy, and it’s defined as unprovoked seizures occurring more than seven days after the injury. The risk depends heavily on how severe the injury was. Studies have found that severe traumatic brain injury increases the risk of epilepsy roughly 17 times compared to the general population. Moderate injuries carry about 3 times the risk, and even mild concussions raise the risk slightly, by about 1.5 times.
Overall, the prevalence of post-traumatic epilepsy ranges from 1% to 53% depending on injury severity and how long patients are followed. The brain’s response to injury, including inflammation, scarring, and changes in blood flow, gradually reshapes neural circuits in ways that can eventually produce seizures. This process can unfold over years, which is why some people develop epilepsy long after their injury has apparently healed.
Stroke and Vascular Causes
Stroke is the leading cause of epilepsy in adults over 65. When a stroke damages brain tissue, either by blocking blood flow or causing bleeding, the injured area can become a source of abnormal electrical activity. Post-stroke seizures can occur in the first week after a stroke or develop months to years later. The distinction matters because early seizures don’t always lead to chronic epilepsy, while later-onset seizures are more likely to recur.
The overlap between stroke risk factors and the aging population means that vascular epilepsy is increasingly common. People who develop seizures after a stroke are already managing other health conditions and medications, which complicates treatment decisions.
Infections
Brain infections are a major cause of epilepsy worldwide, particularly in low- and middle-income countries. The parasite that causes neurocysticercosis, acquired by ingesting eggs from a pork tapeworm, is considered the most common cause of acquired seizures and epilepsy in regions where it’s prevalent, accounting for about 30% of seizure disorders in those areas. The parasite forms cysts in the brain, and the immune response to those cysts triggers seizures.
Bacterial meningitis, viral encephalitis, and other central nervous system infections can also damage brain tissue and lead to chronic epilepsy. The infection itself may resolve completely, but the scarring and structural changes it leaves behind can create lasting seizure susceptibility. HIV, cerebral malaria, and tuberculosis are additional infectious causes that contribute significantly to the global burden of epilepsy.
Immune System Causes
The immune system can sometimes attack the brain by mistake, producing antibodies that target proteins on the surface of neurons. This is called autoimmune encephalitis, and seizures are often one of its earliest and most prominent symptoms. Several specific antibody types have been identified. Antibodies targeting NMDA receptors cause a syndrome involving psychosis, seizures, memory problems, and eventually coma if untreated. This form disproportionately affects young women and is sometimes associated with ovarian tumors.
Other antibodies target GABA receptors, the same inhibitory system that normally prevents seizures. When these receptors are blocked by rogue antibodies, seizures can become severe and difficult to control with standard medications. Identifying an immune cause matters because the treatment is fundamentally different: rather than just suppressing seizures, doctors aim to calm the immune attack itself, which can resolve the epilepsy entirely in some cases.
Metabolic Causes
Certain metabolic disorders disrupt the brain’s energy supply or chemical environment in ways that provoke seizures. These include conditions where the body can’t properly process specific amino acids, fats, or sugars, leading to toxic buildup in the brain. Some metabolic epilepsies are genetic in origin but are classified separately because the seizures stem from a metabolic problem rather than a direct effect on brain cells.
Acute metabolic disturbances like extremely low blood sugar, severe electrolyte imbalances, or organ failure can also trigger seizures. These are typically reversible once the underlying metabolic problem is corrected, and they don’t always lead to a diagnosis of epilepsy unless they cause lasting brain damage.
How Causes Vary by Age
The most likely cause of epilepsy shifts dramatically across the lifespan. In infants and young children, genetic conditions, birth injuries involving oxygen deprivation, and brain malformations formed during development are the primary culprits. In teenagers and young adults, head trauma and brain tumors become more prominent causes. After age 65, stroke and neurodegenerative diseases like Alzheimer’s are the most common triggers.
This age pattern is one reason why a thorough evaluation matters. The testing a neurologist orders for a 5-year-old with new seizures looks quite different from the workup for a 70-year-old, because the most likely causes in each group point toward different diagnostic tools and treatment approaches.