Generalized Tonic-Clonic Seizures Workup

Updated: Dec 31, 2022
  • Author: David Y Ko, MD; Chief Editor: Selim R Benbadis, MD  more...
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Approach Considerations

Patients with generalized tonic-clonic seizures and idiopathic generalized epilepsy typically have no evidence of any localized, regional, or diffuse brain abnormality on history, physical, or neurologic examination; clinical laboratory testing; or imaging studies.

Imaging studies may not be necessary in a small subgroup of patients with a clear history of myoclonic epilepsy and absence, with classic 4- to 5-Hz polyspike and wave and EEG from which the diagnosis of a generalized epilepsy syndrome such as juvenile myoclonic epilepsy can be made with reasonable certainty (along with other supporting evidence, nonfocal neurologic examination findings, and a family history of seizures), because the likelihood of finding an abnormality on imaging is very low.

In practice, however, complete certainty is not possible. Therefore, brain imaging may be obtained in the workup of patients with primary generalized epilepsy if there is a suspicion of focal to bilateral tonic clonic seizures (the secondarily generalized seizures).

Go to EEG in Common Epilepsy Syndromes, Epileptiform Normal Variants on EEG, and Generalized Epilepsies on EEG for information on these topics.



Interictal EEG

The awake EEG of patients with generalized tonic-clonic seizure may be normal. Hyperventilation, photic stimulation, sleep-deprivation and/or prolonged EEG can increase the likelihood of finding an abnormality on EEG.

Interictal abnormalities include usually generalized spikes, sharp waves, polyspikes, and polyspike or spike-and-wave complexes. Paroxysmal frontal intermittent rhythmic delta activity (FIRDA) may be found in some patients, especially those with a history of absences, but this is a nonspecific abnormality that is not considered epileptiform.

Certain specific interictal EEG patterns can be distinctive of generalized epilepsy syndromes, as follows:

  • Generalized bilaterally synchronous 3-Hz spike-and-wave complexes are associated with typical absence attacks

  • Fast spike-and-wave activity at 4-5 Hz is associated most often with generalized tonic-clonic seizures

  • Polyspikes or polyspike and slow-wave complexes usually are seen with juvenile myoclonic epilepsy.

Ictal EEG

The tonic phase of convulsion is characterized by progressively higher amplitude and lower frequency discharge pattern observed simultaneously in both cortical hemispheres, reaching a maximum of 10 Hz.

This then becomes slower and mixed with bilateral high-amplitude spikes and a progressively greater amount of high-amplitude rhythmic delta activity. These are slow, developing progressively into repetitive complexes of high-amplitude spike-and-slow-wave activity in the clonic phase.

Postictal EEG

The postictal EEG may be isoelectric or may show diffuse, very low amplitude, slow delta activity. This corresponds to sustained hyperpolarization.


Prolactin Study

Plasma prolactin levels, if measured within 10-20 minutes of a generalized tonic-clonic seizure, are elevated to 5-30 times the baseline values. The baseline level is obtained at the same time of day when the patient is not seizing. The plasma prolactin level is a useful diagnostic tool to exclude pseudoseizures if the seizure looks like a tonic-clonic seizure. The prolactin level may not be elevated in absence and myoclonic seizures and in simple and brief complex partial seizures.


Other Laboratory Studies

In 15% of patients, especially after a prolonged seizure, cerebrospinal fluid (CSF) pleocytosis may be found (commonly 10 cells/μL and rarely as many as 50 cells/μL).

Metabolic acidosis and elevated levels of serum lactate and creatine kinase are common findings after a seizure.

Serum adrenocorticotropic hormone (ACTH), cortisol, vasopressin, growth hormone, and beta-endorphin levels also are increased postictally but for a very brief duration; therefore, they are not useful clinically.


Computed Tomography

An abnormality on CT scans is rare in patients with primary generalized tonic-clonic seizures. Because CT will not detect most types of congenital structural brain abnormalities, MRI is the imaging modality of choice.


Magnetic Resonance Imaging

Classically, MRIs are normal in primary generalized tonic-clonic seizures. Neuronal migration disorders that may be associated with partial seizures and that may be diagnosed on MRI include the following:

  • Lissencephaly

  • Pachygyria

  • Band or laminar heterotopias

  • Subependymal heterotopias

  • Focal cortical dysplasia polymicrogyria

  • Focal subependymal heterotopias

  • Schizencephaly


Positron Emission Tomography

Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) scans have no role in the workup of generalized tonic-clonic seizures, except if the diagnosis of primary generalized seizure itself is in doubt and usually only when resective surgery is being considered, but that is not a therapy for this type of epilepsy.


Other Tests

If there is a strong family history, or semiology is consistent with certain epilepsy syndromes that are genetic, then genetic testing may be useful. The genetic epilepsies are increasing and the testing costs are decreasing.



The abliity to get ictal studies is increased with ambulatory video EEG and if the events are less frequent then inpatient video EEG where AED can be reduced or withdrawn to induce typical seizue.