Introduction: Who Should Undergo Diagnostics

Anyone who has experienced a seizure episode involving muscle stiffness and jerking movements should seek medical evaluation. This is especially important if it is the first time such an event has occurred, as determining the underlying cause is essential for proper treatment and safety.^[1] The diagnosis process helps doctors understand whether the seizure was an isolated incident triggered by a specific circumstance, or if it represents an ongoing condition like epilepsy that will require long-term management.

People who witness someone having such a seizure should encourage that person to see a healthcare professional, even if they feel fine afterward. This is because the person experiencing the seizure typically loses consciousness and may not remember what happened, making them unaware of the severity of the event.^[4] Diagnostic evaluation becomes particularly urgent if the seizure lasted more than five minutes, if multiple seizures occurred without full recovery between them, or if the person sustained injuries during the fall.

Parents should seek immediate medical attention if their child experiences a seizure, even if it occurs during a fever. While febrile seizures—seizures that happen in the context of fever in young children—are relatively common, proper evaluation is still necessary to rule out other serious causes.^[3] Additionally, pregnant women or those who recently gave birth should seek emergency care if they experience seizures, as this could indicate a serious condition called eclampsia.

Diagnostic evaluation is also advisable for people who experience warning signs before losing consciousness, such as unusual smells, tastes, visual changes, or intense emotions. These symptoms, called an aura, can help doctors understand where in the brain the seizure activity begins.^[3] Even if someone has already been diagnosed with epilepsy, changes in seizure frequency, duration, or characteristics warrant additional diagnostic testing to ensure the treatment plan remains appropriate.

Diagnostic Methods

The journey to diagnosing generalised tonic-clonic seizures begins with a thorough conversation between the patient and their doctor. Because people experiencing these seizures lose consciousness and cannot remember the event, doctors often need to speak with witnesses who saw what happened.^[4] This detailed account helps doctors understand the sequence of events, how long the seizure lasted, what movements occurred, and whether any warning signs appeared beforehand. The more information available, the better doctors can distinguish between different types of seizures and identify potential causes.

Physical and Neurological Examination

A comprehensive physical examination is essential in the diagnostic process. Doctors conduct a detailed neurological exam to assess how well the brain and nervous system are functioning.^[9] This examination tests behavior, the ability to move and control muscles, thinking ability, understanding, and problem-solving skills. By checking reflexes, muscle strength, coordination, sensation, and mental status, doctors can identify signs of underlying brain or nervous system problems that might be causing seizures.

The physical examination also looks for injuries that commonly occur during seizures, such as tongue bites, bruises from falling, or dislocated shoulders. Finding these injuries helps confirm that a seizure actually occurred, especially when no witnesses were present.^[4] Doctors also check for conditions that could trigger seizures, including signs of infection, high blood pressure, or metabolic imbalances.

Electroencephalogram (EEG)

The electroencephalogram, commonly called an EEG, is one of the most important tests for diagnosing seizure disorders. This test measures electrical activity in the brain by placing flat metal discs called electrodes on the scalp.^[9] During the test, which is completely painless, these electrodes detect the tiny electrical signals that brain cells naturally produce when they communicate with each other. In people with seizure disorders, the EEG often shows abnormal patterns of electrical activity, even between seizures when the person feels completely normal.

The EEG can reveal characteristic patterns that help doctors identify the type of seizure disorder. For generalized tonic-clonic seizures, the EEG typically shows abnormal electrical activity occurring simultaneously on both sides of the brain.^[1] Sometimes doctors may recommend a longer EEG recording, lasting several hours or even days, to increase the chances of capturing abnormal brain activity. A special type called high-density EEG uses more electrodes to create a more detailed picture of brain activity patterns.

Blood Tests

Laboratory blood tests play a crucial role in understanding what might have triggered a seizure. Doctors order blood tests to check for various conditions that can provoke seizures, including infections, abnormal blood sugar levels, and electrolyte imbalances—problems with minerals in the blood like sodium, calcium, or magnesium.^[9] Blood tests can also reveal whether someone has diabetes, kidney disease, or liver problems, all of which can increase seizure risk.

In some cases, doctors may also order blood tests to check for genetic conditions or to measure levels of anti-seizure medications if someone is already being treated for epilepsy. A prolactin study—a blood test that measures levels of a hormone called prolactin—can help distinguish true seizures from events that look like seizures but have psychological causes, because prolactin levels rise after true seizures.^[10]

Lumbar Puncture (Spinal Tap)

When doctors suspect that an infection affecting the brain or spinal cord might be causing seizures, they may perform a lumbar puncture, also called a spinal tap. During this procedure, a small sample of cerebrospinal fluid—the liquid that surrounds the brain and spinal cord—is removed for testing.^[9] Laboratory analysis of this fluid can reveal signs of infections like meningitis or encephalitis, both of which can trigger seizures. While the procedure may sound intimidating, it is performed with local anesthesia to minimize discomfort.

Brain Imaging Studies

Imaging tests create detailed pictures of the brain’s structure, helping doctors identify physical abnormalities that might cause seizures. Computed tomography, or CT scanning, uses X-rays and computer processing to create cross-sectional images of the brain.^[9] CT scans are particularly useful in emergency situations because they can be performed quickly and can detect bleeding, strokes, tumors, or other structural problems that might be causing seizures.

Magnetic resonance imaging, known as MRI, provides even more detailed pictures of the brain than CT scans. MRI uses powerful magnets and radio waves rather than X-rays to create images, making it especially good at showing subtle abnormalities in brain tissue.^[9] An MRI can reveal small areas of scarring, abnormal blood vessels, or other changes that might not show up on a CT scan. Many people with epilepsy undergo MRI scanning to look for structural causes of their seizures.

For some patients, doctors may recommend positron emission tomography, or PET scanning. This specialized imaging test can show how different parts of the brain are functioning by detecting how the brain uses sugar for energy.^[9] Areas of the brain where seizures originate often show abnormal patterns of metabolism, even between seizures. PET scans are particularly helpful when doctors are considering surgery as a treatment option and need to pinpoint exactly where seizures are starting.

Additional Specialized Tests

In certain situations, doctors may order additional tests to gather more information. Electrocardiogram, or ECG, records the electrical activity of the heart and can help rule out heart rhythm problems that might cause episodes of losing consciousness that could be mistaken for seizures. Some specialized centers also perform video-EEG monitoring, where patients stay in a hospital unit for several days while their brain activity is continuously recorded along with video of their behavior. This allows doctors to see exactly what happens during a seizure while simultaneously recording the brain’s electrical activity.

Diagnostics for Clinical Trial Qualification

When individuals with generalised tonic-clonic seizures are being considered for participation in clinical trials, they typically undergo more extensive diagnostic testing than in routine clinical practice. These additional tests help researchers ensure that trial participants truly have the condition being studied and that they meet specific criteria designed to make the study results reliable and meaningful.

Potential trial participants usually must have their diagnosis confirmed by a neurologist or epilepsy specialist before enrollment. This confirmation typically requires documented evidence of seizures, which might include EEG recordings showing abnormal brain activity patterns consistent with generalised seizures, as well as witness accounts or video recordings of seizure episodes.^[1] Clinical trials often specify how many seizures a person must have experienced within a certain time period to be eligible, requiring detailed seizure diaries or logs as part of the screening process.

Baseline imaging studies, particularly MRI scans, are commonly required for clinical trial enrollment. These scans serve multiple purposes: they help rule out structural brain abnormalities that might exclude someone from participation, they provide a baseline for comparison if follow-up imaging is done later in the study, and they help ensure the study group is relatively uniform in terms of underlying brain structure.^[9] Some trials may specify that participants cannot have certain types of brain abnormalities, while others might specifically recruit people with particular findings.

Blood tests for trial screening often go beyond basic health assessments. Researchers may check liver and kidney function to ensure participants can safely metabolize the medications or treatments being studied. Blood counts are typically evaluated to establish baseline values and to ensure participants do not have underlying conditions that might interfere with the trial or increase their risk of side effects. For women of childbearing age, pregnancy tests are standard before enrollment since many seizure medications and experimental treatments can harm developing babies.

Cognitive and neuropsychological testing may be part of the qualification process for some clinical trials, particularly those studying new anti-seizure medications or other treatments that might affect thinking, memory, or behavior. These tests establish a baseline level of cognitive function so researchers can monitor whether the treatment being studied has any effects—positive or negative—on mental abilities.

Medication history documentation is crucial for trial enrollment. Researchers typically need detailed information about what anti-seizure medications a person has tried, at what doses, for how long, and whether they were effective or caused side effects. This information helps determine whether someone meets criteria such as having “drug-resistant epilepsy,” which is usually defined as failing to achieve seizure control despite trying at least two appropriate anti-seizure medications.^[10]

Some clinical trials require participants to undergo video-EEG monitoring as part of the qualification process. This extended monitoring session, typically lasting several days in a hospital epilepsy unit, allows researchers to record actual seizure events while simultaneously capturing brain wave patterns. This provides definitive proof of seizure type and can help distinguish generalized seizures from focal seizures that spread to both sides of the brain, which have different treatment implications.

Quality of life questionnaires and depression or anxiety screening tools are increasingly being included in clinical trial diagnostic protocols. These assessments recognize that epilepsy affects more than just seizure frequency—it impacts overall wellbeing, mental health, and daily functioning. Baseline measurements of these factors allow researchers to evaluate whether treatments improve not just seizure control but also overall quality of life.