For roughly half of all people with epilepsy, doctors can identify a specific cause. For the other half, no clear explanation is ever found. That statistic from the World Health Organization can be frustrating to hear, but it doesn’t mean nothing is happening in your brain or that your epilepsy is less real. It means the tools available today can’t always pinpoint the exact trigger. Understanding the known causes can still help you make sense of your diagnosis.
What Happens in the Brain During a Seizure
Your brain runs on a carefully tuned balance between signals that excite nerve cells and signals that calm them down. The main “go” chemical is glutamate, which drives rapid communication between neurons and plays a role in learning and memory. The main “stop” chemical is GABA, which puts the brakes on that activity. In epilepsy, this balance tips too far toward excitation. Neurons fire in synchronized bursts they shouldn’t, producing a seizure.
This imbalance can be caused by many different things, from a structural problem in the brain to a genetic variation that changes how ion channels on nerve cells open and close. Whatever the root cause, the end result is the same: too much electrical activity, not enough suppression. The specific cause shapes what type of seizures you have, how often they occur, and how well they respond to treatment.
Genetic Causes
Some forms of epilepsy run in families. In these cases, changes in specific genes affect how nerve cells communicate or develop. Several well-recognized genetic epilepsy syndromes exist, including genetic epilepsy with febrile seizures plus (GEFS+), familial neonatal epilepsy, and familial focal epilepsy with variable foci. These tend to appear in childhood or infancy, though the age of onset varies by syndrome.
Having a genetic form of epilepsy doesn’t always mean a parent had seizures. Some gene changes arise spontaneously, meaning they weren’t inherited but occurred for the first time in you. Genetic testing, usually through a blood-based gene panel, can sometimes identify a specific mutation. When it does, it may change your treatment approach, since certain genetic epilepsies respond better to particular medications.
Structural Brain Changes
Physical abnormalities in the brain are one of the most identifiable causes. These include malformations of cortical development (where the brain’s outer layer didn’t form correctly before birth), focal cortical dysplasia (a small patch of abnormally organized brain tissue), hippocampal sclerosis (scarring in a memory-related structure deep in the temporal lobe), brain tumors, and vascular malformations.
Some structural causes are present from birth. Others develop later from an injury or illness. Traumatic brain injury is a well-established cause, particularly after a severe blow involving loss of consciousness, skull fracture, or bleeding in the brain. The seizures don’t always start right away. Months or even years can pass between the injury and the first seizure, because the scarring and rewiring process that makes brain tissue prone to seizing unfolds slowly.
High-resolution MRI is the primary tool for spotting these abnormalities. Standard MRI sometimes misses subtle findings, which is why epilepsy specialists use specific scanning protocols designed to detect small areas of dysplasia or scarring that a routine scan would overlook.
Stroke and Epilepsy in Older Adults
Stroke is one of the leading causes of epilepsy in people over 60. Roughly 10% of stroke survivors develop epilepsy afterward, with rates climbing to 10 to 20% after a hemorrhagic stroke (one involving bleeding rather than a clot). The onset is variable, but 40 to 80% of post-stroke epilepsy cases emerge within the first year. The damaged brain tissue left behind by the stroke becomes a focus for abnormal electrical activity, similar to what happens after a traumatic injury.
Infections and Immune System Triggers
Infections that reach the brain can cause lasting damage that leads to epilepsy. Meningitis, encephalitis, and parasitic infections like neurocysticercosis (a tapeworm infection common in parts of the developing world) are all recognized triggers. The seizures may begin during the acute infection or develop later once the infection has cleared but left behind scarring or inflammation.
In autoimmune epilepsy, your immune system attacks healthy brain cells directly. Autoimmune encephalitis is the most common form, and it involves antibodies that target specific receptors on neurons. Rasmussen syndrome, a rarer condition, involves immune cells called T cells causing progressive inflammation and brain damage on one side of the brain. People with other autoimmune diseases, including lupus, Crohn’s disease, rheumatoid arthritis, and thyroid conditions like Hashimoto’s or Graves’ disease, have a higher likelihood of developing autoimmune epilepsy. In some cases, a hidden tumor elsewhere in the body triggers the immune system to mistakenly attack brain tissue, a process called paraneoplastic syndrome.
Autoimmune epilepsy is worth identifying because it often responds poorly to standard seizure medications but may improve significantly with immune-targeted treatments.
Metabolic Conditions
Certain metabolic disorders disrupt the brain’s energy supply or chemical environment enough to cause seizures. These include inborn errors of metabolism, defects in glucose transport (where the brain can’t get enough sugar to function properly), pyridoxine-dependent seizures (a rare condition where the brain needs unusually high amounts of vitamin B6), and mitochondrial diseases that impair how cells produce energy. Most metabolic epilepsies are diagnosed in infancy or childhood, but some milder forms surface later.
How Doctors Search for a Cause
When you’re diagnosed with epilepsy, the workup typically starts with two core tests. An EEG records your brain’s electrical activity through sensors placed on your scalp, helping your neurologist identify what type of seizures you’re having and where in the brain they originate. An MRI scans the brain’s structure to look for tumors, scarring, malformations, or other visible abnormalities.
If those come back normal, further testing may follow depending on your age and the pattern of your seizures. Genetic panels can screen for known epilepsy-related gene changes. Specialized imaging like PET scans or magnetoencephalography (MEG) can sometimes detect seizure-prone areas that standard MRI misses. MEG measures magnetic fields from brain activity and can be more precise than EEG because bone and tissue interfere less with magnetic signals. Blood tests and spinal fluid analysis may be used to check for autoimmune antibodies or signs of infection.
Even with all of these tools, about half of cases remain unexplained. That percentage has been shrinking over the past two decades as genetic testing and imaging technology improve, but it’s still common to go through a full workup and hear that no specific cause was found. Doctors call this “epilepsy of unknown etiology.” It doesn’t change the reality of your seizures or the effectiveness of treatment. Many people with no identifiable cause respond well to medication and live with good seizure control.
Why Not Knowing a Cause Is Common
The brain has roughly 86 billion neurons forming trillions of connections. The processes that tip the excitation-inhibition balance toward seizures can be extraordinarily subtle, involving microscopic changes in ion channels, tiny patches of abnormal tissue too small for current imaging to detect, or complex interactions among multiple genes that no single test captures. The “unknown” category isn’t a dead end. It’s a reflection of where the science stands right now. For many people, the practical focus shifts from identifying the cause to finding the treatment that controls seizures most effectively with the fewest side effects.