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Generalized Tonic-Clonic Seizures Workup

  • Author: David Y Ko, MD; Chief Editor: Selim R Benbadis, MD  more...
Updated: Jun 30, 2015

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.

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 is often normal. Hyperventilation, photic stimulation, and sleep-deprived 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.

Contributor Information and Disclosures

David Y Ko, MD Associate Professor of Clinical Neurology, Associate Director, USC Adult Epilepsy Program, Keck School of Medicine of the University of Southern California

David Y Ko, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, American Headache Society, American Clinical Neurophysiology Society

Disclosure: Received honoraria from UCB for speaking and teaching; Received consulting fee from Lundbeck for consulting; Received consulting fee from Westward for consulting; Received consulting fee from Esai for consulting; Received consulting fee from Supernus for consulting; Received consulting fee from Sunovion for speaking and teaching.


Soma Sahai-Srivastava, MD Director of Neurology Ambulatory Care Services, LAC and USC Medical Center; Assistant Professor, Department of Neurology, Keck School of Medicine of the University of Southern California

Soma Sahai-Srivastava, MD is a member of the following medical societies: American Academy of Neurology, American Medical Association, American Headache Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Jose E Cavazos, MD, PhD, FAAN, FANA, FACNS Professor with Tenure, Departments of Neurology, Pharmacology, and Physiology, Assistant Dean for the MD/PhD Program, Program Director of the Clinical Neurophysiology Fellowship, University of Texas School of Medicine at San Antonio; Co-Director, South Texas Comprehensive Epilepsy Center, University Hospital System; Director, San Antonio Veterans Affairs Epilepsy Center of Excellence and Neurodiagnostic Centers, Audie L Murphy Veterans Affairs Medical Center

Jose E Cavazos, MD, PhD, FAAN, FANA, FACNS is a member of the following medical societies: American Academy of Neurology, American Clinical Neurophysiology Society, American Neurological Association, Society for Neuroscience, American Epilepsy Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Brain Sentinel, consultant.<br/>Stakeholder (<5%), Co-founder for: Brain Sentinel.

Chief Editor

Selim R Benbadis, MD Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida College of Medicine

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Medical Association, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cyberonics; Eisai; Lundbeck; Sunovion; UCB; Upsher-Smith<br/>Serve(d) as a speaker or a member of a speakers bureau for: Cyberonics; Eisai; Glaxo Smith Kline; Lundbeck; Sunovion; UCB<br/>Received research grant from: Cyberonics; Lundbeck; Sepracor; Sunovion; UCB; Upsher-Smith.

Additional Contributors

Ramon Diaz-Arrastia, MD, PhD Professor, Department of Neurology, University of Texas Southwestern Medical Center at Dallas, Southwestern Medical School; Director, North Texas TBI Research Center, Comprehensive Epilepsy Center, Parkland Memorial Hospital

Ramon Diaz-Arrastia, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, New York Academy of Sciences, Phi Beta Kappa

Disclosure: Nothing to disclose.

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