Tonic-clonic seizures happen when the brain’s normal electrical activity is disrupted by a sudden imbalance between excitation and inhibition in nerve cells. This can be caused by genetics, brain injuries, metabolic problems, infections, substance withdrawal, or sometimes no identifiable cause at all. Understanding the specific trigger matters because it shapes how seizures are managed and whether they’re likely to recur.
What Happens in the Brain During a Seizure
Your brain cells communicate through a careful balance of excitatory and inhibitory signals. The main excitatory chemical messenger is glutamate, which tells neurons to fire. The main inhibitory one is GABA, which tells them to stop. A tonic-clonic seizure occurs when excitation overwhelms inhibition, causing massive, uncontrolled electrical firing that spreads across both hemispheres of the brain.
During the tonic phase, this electrical storm causes every muscle in the body to stiffen at once. The brain’s electrical activity ramps up to a rapid rhythm of about 10 cycles per second. Then, during the clonic phase, the firing pattern shifts to slower bursts that cause rhythmic jerking of the limbs. The electrical activity gradually slows to about 1 cycle per second before the seizure ends, followed by a period of suppressed brain activity that corresponds to the confusion and exhaustion most people feel afterward.
This imbalance can originate from problems at several levels: faulty wiring between brain circuits, dysfunctional receptors on nerve cells, or ion channels that don’t open and close properly. The root cause determines whether someone has a single seizure or develops epilepsy.
Genetic Causes
Many cases of generalized tonic-clonic seizures have a genetic basis, though the genetics are rarely simple. Most adult-onset epilepsies involve multiple gene defects working together to create excessive excitability, reduced inhibition, or both.
One well-studied example involves the SCN1A gene, which controls sodium channels in nerve cells. Mutations in this gene are inherited in an autosomal dominant pattern, meaning a child needs only one copy of the faulty gene (from one parent) to be affected. Other genes linked to generalized tonic-clonic seizures include CLCN2, which affects chloride channels, and SLC2A1, which affects how glucose is transported into the brain. Some genetic forms follow an autosomal recessive pattern, requiring faulty copies from both parents, as seen with mutations in the TBC1D24 gene.
Having a family history of epilepsy increases your risk, but many people with genetic epilepsy have no affected relatives. Spontaneous mutations that weren’t inherited from either parent can also be responsible.
Structural Brain Damage
Any injury or abnormality that disrupts the brain’s architecture can trigger tonic-clonic seizures. The damaged tissue creates areas of abnormal electrical activity that can spread and overwhelm normal brain function.
Common structural causes include:
- Stroke: damaged brain tissue from blocked or bleeding blood vessels becomes a source of abnormal electrical activity
- Traumatic brain injury: scar tissue from head trauma can trigger seizures months or even years after the original injury
- Brain tumors: both cancerous and noncancerous growths can irritate surrounding brain tissue
- Malformed blood vessels: abnormal tangles of blood vessels present from birth can disrupt nearby circuits
- Neurodegenerative diseases: conditions like Alzheimer’s disease progressively damage brain tissue and can lower the seizure threshold
Infections That Affect the Brain
Infections that cause inflammation in the brain or its surrounding membranes are a significant cause of tonic-clonic seizures, particularly in lower-income countries. Encephalitis (inflammation of the brain itself) and meningitis (inflammation of the membranes around the brain) can both provoke seizures during the acute illness. Even after the infection resolves, the scarring left behind can create a long-term seizure risk.
Metabolic and Electrolyte Imbalances
The brain is extremely sensitive to changes in blood chemistry. When certain levels fall too low or climb too high, nerve cells become unstable and fire inappropriately.
Sodium imbalances are a common culprit. Levels below 120 mmol/L (severely low) can progress from nausea and dizziness to full seizures. But correcting low sodium too quickly is also dangerous: rapid rehydration can cause brain swelling that itself triggers seizures. High sodium levels carry their own seizure risk through a different mechanism.
Calcium works similarly in both directions. Severely low calcium destabilizes nerve cell membranes, making them more likely to fire spontaneously. High calcium can also cause seizures. Blood sugar extremes are another major trigger. Up to 25% of people with very high blood sugar (hyperglycemia) experience seizures, while about 7% of those with very low blood sugar do. In one pattern, extremely high blood sugar without the presence of ketones causes a condition that often produces focal seizures that can spread into full tonic-clonic events. These seizures typically resolve once blood sugar is corrected.
Metabolic causes are especially important in infants, where low calcium and blood sugar abnormalities are among the most common triggers for acute seizures.
Alcohol and Substance Withdrawal
Alcohol withdrawal is one of the most common causes of tonic-clonic seizures in adults. Chronic alcohol use suppresses brain excitability over time, and the brain compensates by becoming more excitable at baseline. When alcohol is suddenly removed, the brain’s heightened excitability is unmasked, and the seizure threshold drops dramatically.
The danger window is well defined. Seizures most commonly appear 6 to 48 hours after the last drink, and more than 90% occur within the first 48 hours. If a seizure happens more than 48 hours after someone stops drinking, other causes like a head injury or withdrawal from additional substances should be investigated. These seizures are a medical emergency because they can progress to a cluster of repeated seizures or a prolonged seizure that doesn’t stop on its own.
Withdrawal from certain medications, particularly benzodiazepines and barbiturates, can trigger seizures through a similar mechanism.
Fever-Related Seizures in Children
Febrile seizures are the most common type of seizure in childhood, affecting 2% to 5% of children in the U.S. and Europe. They typically occur between 6 months and 5 years of age, with the highest risk between 12 and 18 months. Boys are affected slightly more often than girls, at a ratio of about 1.6 to 1.
These seizures happen when a fever above 100.4°F (38°C) occurs, though there’s no single temperature that guarantees a seizure. Every child has a different threshold, and some children seize at relatively modest fevers while others tolerate high fevers without any neurological effects. The rate of temperature rise may matter as much as the peak temperature itself. Febrile seizures are generally tonic-clonic in nature and, while frightening to witness, are usually brief and don’t cause lasting brain damage.
Sleep Deprivation and Lifestyle Triggers
Sleep deprivation is one of the most reliable triggers for tonic-clonic seizures in people who are already susceptible. Lack of sleep increases the brain’s baseline excitability and lowers the seizure threshold. This is why neurologists sometimes use sleep deprivation deliberately before an EEG to increase the chances of capturing abnormal brain activity during testing.
The connection between sleep and seizures is particularly strong in certain epilepsy syndromes. In juvenile myoclonic epilepsy, for instance, tonic-clonic seizures typically strike shortly after waking up, especially after a night of poor or shortened sleep. Forced early awakening is a known precipitant. Other lifestyle factors that can lower the seizure threshold include excessive stress, missed meals, illness, and in some people, flashing or flickering lights.
When No Cause Is Found
In a significant number of people who develop tonic-clonic seizures, no specific structural, metabolic, or infectious cause can be identified through standard testing. These cases are classified as idiopathic or genetic generalized epilepsy, meaning the underlying cause is presumed to be genetic even when specific gene mutations haven’t been pinpointed. The diagnosis is made based on the pattern of seizures and characteristic findings on an EEG, which typically shows generalized spike-and-wave discharges between seizures. For many of these individuals, seizures respond well to medication, but the lack of a clear structural cause can be frustrating for patients looking for a definitive explanation.