eMedicine Specialties > Neurology > Seizures and Epilepsy

Generalized Tonic-Clonic Seizures: Differential Diagnoses & Workup

Author: David Y Ko, MD, Associate Professor, Department of Neurology, University of Southern California Keck School of Medicine
Coauthor(s): Soma Sahai-Srivastava, MD, Director of Neurology Ambulatory Care Services, LAC and USC Medical Center; Assistant Professor, Department of Neurology, University of Southern California
Contributor Information and Disclosures

Updated: May 6, 2009

Differential Diagnoses

Other Problems to Be Considered

Hyperventilation and electrolyte imbalances
Prolonged QT syndrome and other arrhythmias
Dystonias including nocturnal paroxysmal dystonias
Paroxysmal dyskinesias²
Encephalopathies and metabolic disorders
Pseudoepileptic seizures
Nocturnal paroxysmal events (eg, sleep apnea, night terrors)²
Paroxysmal abnormalities of tone (eg, opisthotonic posturing and clonus)
In infants, apneic syndromes including gastroesophageal reflux and jitteriness of the newborn
In toddlers and young school-aged children, simple faints and breath-holding spells²

Workup

Laboratory Studies

• Plasma prolactin levels, if investigated within 10-20 minutes of a generalized tonic-clonic seizure, are elevated 5-30 times the baseline values. The plasma prolactin level is a useful diagnostic tool to exclude pseudoseizures if the seizure looks like a tonic-clonic seizure. Prolactin level may not be elevated in absence and myoclonic seizures and in simple and brief complex partial seizures.
• 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.
• In 15% of patients, especially after a prolonged seizure, cerebrospinal fluid (CSF) pleocytosis may be found (commonly 10 cells/mm³ and rarely as many as 50 cells/mm³).
• Metabolic acidosis and elevated levels of serum lactate and creatine kinase are common findings after a seizure.

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 like 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 is the next step in the workup of patients with epilepsy.
• 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.
• Neuronal migration disorders that may be diagnosed on MRI include lissencephaly, pachygyria, band or laminar heterotopia, subependymal heterotopias, focal cortical dysplasia polymicrogyria, focal subependymal heterotopias, and schizencephaly.
• 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.

Other Tests

• Interictal EEG
  • The awake EEG of patients with generalized tonic-clonic seizure is often normal. Interictal abnormalities include spikes, sharp waves, polyspikes, and polyspike or spike-and-wave complexes.
  • Hyperventilation, photic stimulation, and sleep-deprived EEG can increase the likelihood of finding an abnormality on EEG.
  • 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: (1) generalized bilaterally synchronous 3-Hz spike-and-wave complexes are associated with typical absence attacks; (2) fast spike-and-wave activity at 4-5 Hz is associated most often with generalized tonic-clonic seizures; (3) 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.
• 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.

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