Focal seizures start from abnormal electrical activity in one specific area of the brain, and they account for roughly 61% of all epilepsy cases. Their causes range from structural damage like tumors and stroke to genetic mutations, infections, and autoimmune conditions. In many cases, the cause shifts depending on your age, with infections more common in younger adults and stroke dominating in people over 55.
Structural Brain Lesions
Structural brain lesions are the most common cause of focal seizures in adults. These include brain tumors, areas of abnormal brain development present from birth (called cortical dysplasia), blood vessel malformations, and scar tissue from prior injuries. Not all lesions carry the same risk. Infiltrating tumors, which grow into surrounding brain tissue, are more likely to cause seizures than damage from a stroke. Lesions in the outer layer of the brain (the cortex) carry a higher seizure risk than those deeper inside, and tumors in the temporal and frontal lobes are particularly prone to triggering seizures.
Where the lesion sits also affects how the seizure behaves. Lesions in the right frontal cortex, for example, carry more than four times the odds of a focal seizure spreading to both sides of the brain compared to lesions elsewhere. Cortical lesions in general were more likely to produce these spreading seizures than subcortical ones (65% vs. 44%).
Traumatic Brain Injury
A blow to the head can set the stage for focal seizures months or even years later. The risk scales with injury severity. After a focal brain injury, such as a localized bruise or bleed, roughly 52% of people who have a post-traumatic seizure go on to develop epilepsy. That number drops to about 27% for mild injuries. Timing matters too: when the first seizure occurs within two years of the injury, the risk of developing ongoing epilepsy is close to 49%, compared to 36% when it happens later.
The underlying process involves a slow cascade of changes in the damaged tissue. Inflammation, the formation of scar tissue, and the loss of inhibitory nerve cells all gradually rewire the local circuitry until it becomes prone to spontaneous firing. This is why seizures often don’t appear immediately after the injury but develop over a latency period.
Stroke
Stroke is the leading cause of new-onset seizures in older adults. In one study of patients over 55 presenting with first-time seizures, more than 83% had experienced a stroke. The risk is highest when the stroke affects the front half of the brain’s blood supply rather than the back, and it peaks during the first two years after the event before gradually declining. Like traumatic brain injury, the damaged tissue undergoes changes that create a focus of hyperexcitable neurons capable of triggering seizures on their own.
Genetic Causes
Some focal seizures run in families. One well-characterized condition, familial focal epilepsy with variable foci, is caused by mutations in genes called DEPDC5, NPRL2, or NPRL3. These genes normally produce proteins that form a complex responsible for keeping a key growth-signaling pathway in check. When any one of these genes is mutated, the pathway becomes overactive, leading to abnormal development of the connections between nerve cells and excessive nerve cell firing.
The condition follows an autosomal dominant inheritance pattern, meaning a single copy of the altered gene is enough to cause it. Still, not everyone who carries the mutation develops seizures. About 60% of people with DEPDC5 mutations eventually develop the condition. In many cases, different family members experience seizures originating from different brain regions, which is what gives the syndrome its “variable foci” name. Beyond this specific syndrome, many other genetic variations can increase seizure susceptibility, though genes are usually only part of the picture.
Infections and Autoimmune Conditions
Brain infections are a significant cause of focal seizures, especially in younger adults. Bacterial meningitis, viral encephalitis, tuberculosis affecting the brain, and parasitic infections like cerebral malaria can all damage specific brain regions and create a seizure focus. In younger patients (ages 13 to 35), infections collectively account for the majority of new-onset seizure cases.
Autoimmune conditions are an increasingly recognized cause. In autoimmune encephalitis, the immune system produces antibodies that attack proteins on the surface of brain cells. Antibodies targeting NMDA receptors or a protein called LGI1 are classic examples. Anti-LGI1 antibodies can produce a distinctive seizure type called faciobrachial dystonic seizures, involving brief, repetitive jerking movements of the face and arm. Rasmussen encephalitis, another immune-mediated condition, involves immune cells directly attacking one hemisphere of the brain, causing progressive focal seizures and neurological decline, primarily in children.
How Causes Shift With Age
The most likely cause of a focal seizure depends heavily on how old you are. In children and young adults, infections, genetic conditions, and structural brain abnormalities present from birth are the leading culprits. In middle-aged adults (roughly 36 to 55), stroke begins to emerge as a major player, responsible for about 37% of new-onset seizures in that group, alongside metabolic disturbances like dangerously low sodium, calcium, or blood sugar levels. By age 55 and older, stroke is overwhelmingly dominant, causing the vast majority of first-time seizures.
What Happens in the Brain During a Focal Seizure
Regardless of the underlying cause, focal seizures share a common final pathway: an imbalance between excitatory and inhibitory signaling in a localized group of neurons. The brain’s main inhibitory chemical, GABA, normally acts as a brake on nerve cell firing. It works by opening channels that allow chloride ions to flow into cells, which quiets them down. The brain’s main excitatory chemical, glutamate, does the opposite, ramping neurons up.
In a seizure focus, this balance tips toward excitation. Several things can make that happen. The loss of inhibitory nerve cells reduces GABA release. Glutamate levels rise during seizure activity while GABA levels stay flat, shifting the ratio further. Under certain pathological conditions, including oxygen deprivation at birth, the direction of chloride flow can actually reverse, turning GABA from a calming signal into an excitatory one. This reversal involves changes in two molecular pumps that control chloride levels inside cells.
Prolonged seizure activity makes the problem worse in real time. During sustained seizures, the brain’s GABA receptors get pulled inside the cell and temporarily shut down, which is why certain medications become less effective the longer a seizure continues.
Triggers Are Not Causes
It helps to distinguish between what causes focal seizures and what triggers them. A cause is the underlying condition that makes the brain prone to seizing: a tumor, scar tissue, a genetic mutation. A trigger is something that lowers the threshold in someone who already has that underlying vulnerability. Common triggers include sleep deprivation, high stress, missed medication, illness or fever, and hormonal changes during menstruation.
Most people with epilepsy don’t have a single reliable trigger that always produces a seizure. But tracking patterns can be useful. Keeping a log of when seizures happen, along with notes on sleep, stress, medication, and menstrual cycles, can help identify factors that make seizures more likely for you specifically.
Finding the Cause With Imaging
When someone presents with focal seizures, brain MRI is the primary tool for identifying a structural cause. But the quality of the scan and the expertise of the person reading it matter enormously. In one landmark study, standard MRI reports read by non-specialists detected focal lesions only 39% of the time. When epilepsy specialists read the same standard scans, detection improved to 50%. And when those specialists read scans taken with epilepsy-specific MRI protocols (thinner slices, specific sequences), sensitivity jumped to 91%. For temporal lobe epilepsy specifically, MRI picks up abnormalities 90 to 97% of the time, but that rate drops for seizures originating outside the temporal lobe, where the structural changes can be extremely subtle.
This gap means that if a standard MRI comes back normal, it doesn’t necessarily rule out a structural cause. Requesting an epilepsy-protocol MRI read by a specialist can make the difference between identifying a treatable lesion and being told the cause is unknown.