What Causes Epilepsy in Adults: Stroke, Tumors & More

Stroke is the single most common identified cause of epilepsy in adults, particularly after middle age, but the full list of triggers is surprisingly long. A large population-based study found that stroke accounted for about 30% of all adult-onset unprovoked seizures and rose to 45% in people over 60.¹ Brain tumors, head injuries, infections, autoimmune conditions, neurodegenerative diseases, genetics, and even alcohol withdrawal all make the list. In roughly a quarter of cases, doctors never pin down a cause at all, which tells you how much remains to be understood about why a previously healthy adult brain starts generating seizures.

How Stroke Leads to Epilepsy

Stroke dominates the statistics for adult-onset epilepsy, and the risk climbs steeply with age. In one study, over 95% of patients with post-stroke seizures were older than 40.² A retrospective analysis spanning 25 years confirmed that the proportion of epilepsy attributable to cerebrovascular disease increased consistently with age at onset, and structural epilepsy was the predominant category in patients over 51.³

What happens in the brain after a stroke is not a single event but a drawn-out cascade. The initial injury kills neurons, but the damage keeps rippling outward. Scar tissue forms, the blood-brain barrier breaks down, and the surviving neural networks rewire in ways that make them prone to firing abnormally. Inflammation, oxidative stress, and shifts in how brain cells handle excitatory signals all contribute to turning a one-time injury into a permanently hyperexcitable circuit.⁴ This process can take months or even years, which is why someone might have a stroke at 60 and develop epilepsy at 63.

Not every stroke carries the same seizure risk. Hemorrhagic strokes, which involve bleeding into the brain, tend to be more epileptogenic than ischemic strokes, where a clot blocks blood flow. Location matters too: strokes affecting the cerebral cortex carry a higher risk than those buried deep in the brain’s white matter. Vascular malformations, which are abnormal tangles of blood vessels, can also cause seizures through a similar set of mechanisms including neuronal loss and altered neurotransmitter levels in the surrounding cortex.⁵

Brain Tumors and Seizures

Tumors account for roughly 11% of adult-onset unprovoked seizures overall, making them the second most commonly identified structural cause after stroke.¹ In many cases, a seizure is actually the first symptom that leads to the tumor’s discovery. Slow-growing tumors like low-grade gliomas are more likely to cause epilepsy than fast-growing ones, partly because they have more time to reshape the brain tissue around them.

The mechanism is distinct from stroke. Gliomas actively release high levels of glutamate, the brain’s main excitatory chemical, through specialized transport systems. This floods the surrounding tissue and makes it abnormally excitable. The problem is compounded because the astrocytes near the tumor, which normally mop up excess glutamate, become dysfunctional and lose their ability to clear it. Immune cells in the area can also start releasing additional glutamate in response to signals from the tumor.⁶ The result is a zone of chronically over-excited brain tissue surrounding the tumor itself. This is why seizures from brain tumors often originate not in the tumor but in the ring of disrupted cortex around it.

Traumatic Brain Injury

A severe head injury is one of the strongest predictors of developing epilepsy later in life, and the risk stays elevated for years. In a study of patients surviving severe traumatic brain injury, a quarter developed epilepsy within five years, and about a third did so within fifteen years.⁷ Among those who had even a single late seizure, meaning one that occurred more than a week after the injury, the chance of having more seizures was about 62% within a year and 82% within a decade.

The severity and type of injury matter enormously. Penetrating injuries carry a much higher epilepsy risk than closed-head trauma. Independent risk factors identified in that same study included the patient’s age, whether they required a type of surgery called decompressive hemicraniectomy (where part of the skull is temporarily removed to relieve swelling), and whether an intracranial infection developed after the injury.⁷ Mild concussions, by contrast, raise the risk only modestly and primarily in the first few years.

Brain Infections

Not all infections of the brain carry equal epilepsy risk, and the differences are dramatic. A large population-based study compared the ten-year risk of epilepsy across different types of brain infections. After tick-borne encephalitis, the risk was under 2%. After bacterial meningitis, it was about 4%. But after herpes simplex virus encephalitis, the risk jumped to 26%, and after a brain abscess, it hit 30%.⁸ For comparison, the rate in matched healthy controls over the same period was just 1.2%.

The pattern makes intuitive sense. Infections that cause more direct destruction of brain tissue, such as herpes encephalitis (which has a particular affinity for the temporal lobes) and abscesses (which are essentially pockets of pus that erode surrounding brain), leave behind more scarring and disruption. Infections that primarily inflame the membranes around the brain without deeply invading the tissue itself tend to carry a lower, though still elevated, risk. In younger adults, central nervous system infections were actually one of the more common identifiable causes of new-onset seizures, second only to idiopathic cases in those under 40.²

Autoimmune Epilepsy

This is one of the most important developments in epilepsy research over the past two decades. Doctors now recognize that the immune system can produce antibodies that directly attack proteins on the surface of brain cells, making those cells hyperexcitable and disrupting normal signaling.⁹ The most well-known example is anti-NMDA receptor encephalitis, which gained public attention after journalist Susannah Cahalan described her experience in a best-selling memoir. But there are now several recognized antibody types, each targeting different receptor proteins.

Autoimmune epilepsy matters for a practical reason: it responds to immunotherapy rather than standard seizure medications. If the antibodies are suppressed, the seizures often stop. This makes correct identification genuinely life-changing, yet autoimmune causes are still frequently missed on initial evaluation, especially in older adults where seizures are more reflexively attributed to stroke or degeneration. Antibody testing is not always part of the routine workup, so if seizures resist standard treatment and no structural cause is found, asking about autoimmune testing is worth doing.

Neurodegenerative Disease

Alzheimer’s disease is the neurodegenerative condition most clearly linked to epilepsy, accounting for about 7% of unprovoked seizures in adults in one population study.¹ The relationship between the two conditions runs deeper than coincidence. Experimental research shows that the hallmark proteins of Alzheimer’s, amyloid and tau, can push brain cells toward hyperexcitability even before clinical symptoms of dementia appear, partly by disrupting the balance between excitatory and inhibitory neurons.¹⁰

Imaging studies have added a striking detail. In Alzheimer’s patients who develop seizures, the brain hemisphere where the seizures originate shows significantly more tau protein buildup, more amyloid deposition, and more tissue loss compared to the opposite hemisphere.¹¹ Compared with Alzheimer’s patients without seizures, those with epilepsy also had greater overall amyloid burden. The relationship appears to be bidirectional: Alzheimer’s pathology promotes seizures, and seizure activity may in turn accelerate neurodegeneration. This feedback loop is one reason epilepsy in older adults with cognitive decline deserves aggressive treatment.

Genetic Causes That Surface in Adulthood

Genetic epilepsy is often thought of as a childhood condition, but that assumption is increasingly outdated. The success rate of genetic testing in adults with epilepsy and related neurodevelopmental features ranges from about 23% to 50%, comparable to what clinicians find in children.¹² The specific genes implicated differ somewhat between adult-onset and childhood-onset cases, though one gene, SCN1A, turns up as the most commonly implicated in both groups.

A genetic finding can change treatment directly. Some gene variants respond better to specific medications or are actually worsened by drugs that would seem reasonable to prescribe without genetic information. For adults with unexplained epilepsy, especially those whose seizures started in adolescence or early adulthood and who have not responded well to standard treatments, genetic testing is becoming a more routine consideration rather than a last resort.

Alcohol Withdrawal and Metabolic Triggers

Alcohol withdrawal seizures are among the most common acute seizure triggers in adults, distinct from epilepsy in the traditional sense but frequently encountered in emergency departments. When someone who has been drinking heavily for an extended period suddenly stops, the brain is left in a state of unchecked excitability. Chronic alcohol exposure dampens the brain’s excitatory pathways and enhances its inhibitory ones; abrupt withdrawal strips away those compensations all at once. The resulting seizures are typically generalized tonic-clonic, the kind most people picture when they think of a seizure, involving full-body convulsions.¹³

Other metabolic disturbances can also lower the seizure threshold in adults without any underlying brain lesion. Severe drops in blood sodium, blood sugar, or calcium can all trigger seizures. Kidney failure, liver failure, and certain medications (including some antibiotics, antidepressants, and stimulants) are well-known offenders. These are considered provoked seizures, meaning they have an identifiable and often reversible trigger, and they do not necessarily lead to a diagnosis of epilepsy. The distinction matters because treating the metabolic problem usually stops the seizures without requiring long-term anti-seizure medication.

The Blood-Brain Barrier as a Common Thread

One of the more useful ways to understand why such different injuries and diseases all lead to the same outcome is to look at the blood-brain barrier. This barrier normally keeps blood proteins and immune cells out of the brain. When it breaks down, which happens after stroke, head injury, infection, and even prolonged seizure activity, blood proteins (particularly albumin) leak into brain tissue. This leakage sets off a chain reaction in the supporting cells of the brain, impairing their ability to regulate the chemical environment around neurons and triggering inflammation.¹⁴ Immune cells from the bloodstream then enter the brain, amplifying the inflammation and causing further barrier damage, creating a self-perpetuating cycle.¹⁵

This shared pathway helps explain a frustrating clinical reality: once the process of epileptogenesis begins, it can become self-sustaining even after the original insult has resolved. The stroke heals, the infection clears, the tumor is removed, but the barrier damage and resulting neural rewiring persist. Researchers are actively investigating whether targeting barrier repair or the inflammatory cascade could prevent epilepsy from developing after a brain injury, but no drug has yet been proven to do this in humans.

When No Cause Can Be Found

Despite modern imaging and laboratory testing, the cause of adult-onset epilepsy remains unidentified in a substantial fraction of cases. Estimates for this “cryptogenic” category hover around 25% to 40% of adult-onset epilepsies.¹⁶ This is not just an academic classification problem. Cryptogenic epilepsy carries a higher rate of drug-resistant seizures compared to epilepsy with an identified cause: roughly 40% of cryptogenic cases resist medication versus about 26% of those labeled idiopathic.¹⁶

Researchers studying late-onset cryptogenic epilepsy have identified at least three recognizable subgroups. One resembles transient epileptic amnesia, where the main symptom is brief episodes of memory loss rather than convulsions. Another involves temporal lobe seizures with a tendency toward rapid progression and resistance to medication. A third involves seizures originating outside the temporal lobe.¹⁷ Imaging studies of these patients have found structural differences in brain regions like the amygdala and hippocampus that standard MRI protocols might miss, suggesting that at least some “unknown cause” cases involve subtle abnormalities below the resolution of routine scans.¹⁸

Advanced imaging techniques are steadily shrinking this unknown category. In cases where standard MRI is negative but seizures persist, tools like PET scans, functional MRI, and specialized analysis of brain tissue texture can reveal abnormalities invisible on routine imaging.¹⁹ For people considering surgery to treat drug-resistant epilepsy, this multimodal imaging approach is especially valuable, since finding the seizure source on a scan significantly improves the odds of a good surgical outcome.²⁰

Epilepsy After Brain Surgery

It may seem paradoxical, but brain surgery itself can cause epilepsy, even when the surgery is performed for an unrelated condition. A nationwide cohort study found that the overall one-year risk of developing new epilepsy after a craniotomy was about 14%. The risk varied by the reason for surgery: roughly 15% for those undergoing tumor removal, about 11% for both spontaneous and traumatic brain hemorrhages, and a striking 28% for patients who had surgery for a brain abscess.²¹ These numbers are high enough that post-surgical seizure monitoring is standard practice, though prophylactic anti-seizure medication is not universally recommended and varies by institution.

Hormonal Influences on Seizure Patterns

Hormones do not typically cause epilepsy from scratch, but they can significantly modulate seizure frequency in people who already have it. Estrogen tends to lower the seizure threshold, while progesterone has the opposite effect. This interplay produces what is called catamenial epilepsy, a pattern where seizures cluster around specific phases of the menstrual cycle.²² Roughly a third of women with epilepsy report some degree of menstrual-related seizure fluctuation.

Menopause adds another layer of complexity. Although the overall seizure burden does not consistently worsen or improve during menopause when looking at averages across all women, individual women frequently report changes in either direction. The hormonal shifts of perimenopause and postmenopause are associated with altered seizure patterns for a meaningful subset of patients.²³ Hormone replacement therapy can also affect seizure control, making it a conversation worth having with a neurologist rather than managing independently.

Sudden Unexpected Death in Epilepsy

One of the most serious long-term risks of epilepsy that many adults are never told about is SUDEP, or sudden unexpected death in epilepsy. The incidence in adults is roughly 1.2 per 1,000 patient-years.²⁴ That translates to a small but real cumulative risk over a lifetime of living with the condition.

The single strongest risk factor is having generalized tonic-clonic seizures. One large case-control study found that having these seizures at all in the preceding year was associated with a 27-fold increased risk, while having only non-tonic-clonic seizures carried no excess risk at all.²⁵ The risk also rises with seizure frequency: having more than 50 seizures per year was linked to about a tenfold increase compared with having two or fewer.²⁶

Living arrangements appear to matter. Living alone was associated with a fivefold increase in SUDEP risk, and the combination of living alone and having tonic-clonic seizures carried a dramatically higher risk than either factor alone.²⁵ Nocturnal seizures also add risk, likely because they go unwitnessed. The practical upshot is straightforward: the most effective way to reduce SUDEP risk is to control tonic-clonic seizures as aggressively as possible, and for people who continue having them, not sleeping alone and using seizure-detection devices may offer some additional protection.

1
PubMed. Incidence and clinical characterization of unprovoked seizures in adults: a prospective population-based study
2
PubMed Central. Adult onset seizures: Clinical, etiological, and radiological profile
3
PubMed Central. Etiologies of patients with adult-onset epilepsy over the past 25 years: a retrospective study in China
4
PubMed Central. Epileptogenesis After Stroke: Current Insights Into Molecular and Structural Mechanisms
5
PubMed. Vascular malformations and epilepsy: clinical considerations and basic mechanisms
6
PubMed Central. Glutamate and tumor-associated epilepsy: glial cell dysfunction in the peritumoral environment
7
PubMed Central. Risk Factors and Incidence of Epilepsy after Severe Traumatic Brain Injury
8
PubMed. Epilepsy after brain infection in adults: A register-based population-wide study
9
JCI Insight. Autoimmune seizures and epilepsy
10
Current neurology and neuroscience reports. The Bidirectional Relationship Between Epilepsy and Alzheimer’s Disease
11
PubMed Central. Association of Seizure Foci and Location of Tau and Amyloid Deposition and Brain Atrophy in Patients With Alzheimer Disease and Seizures
12
PubMed Central. Monogenic Epilepsies in Adult Epilepsy Clinics and Gene-Driven Approaches to Treatment
13
PubMed Central. Update on the neurobiology of alcohol withdrawal seizures
14
PubMed Central. The Role of Blood-Brain Barrier Disruption in Epilepsy: Mechanisms and Consequences
15
PubMed Central. Blood‑brain barrier dysfunction in epilepsy: Mechanisms, therapeutic strategies and future orientation
16
IntechOpen. Emerging Trends in the Management of Cryptogenic Epilepsy
17
PubMed. Clinical features of late-onset partial cryptogenic epilepsy: toward an idiopathic temporal epilepsy?
18
PubMed. Brain morphological and microstructural features in cryptogenic late-onset temporal lobe epilepsy: a structural and diffusion MRI study
19
PubMed. Neuroimaging in Adults and Children With Epilepsy
20
PubMed. Imaging for Adults With Seizures and Epilepsy
21
PubMed Central. Postoperative de novo epilepsy after craniotomy: a nationwide register-based cohort study
22
PubMed Central. Hormonal aspects of epilepsy
23
PubMed. Effects of menopause on seizures in women with epilepsy
24
PubMed. Practice guideline summary: Sudden unexpected death in epilepsy incidence rates and risk factors
25
PubMed Central. Clinical risk factors in SUDEP: A nationwide population-based case-control study
26
The Lancet. Risk factors for sudden unexpected death in epilepsy: a case-control study