Generalized Tonic-Clonic Seizures

Updated: Dec 31, 2022
  • Author: David Y Ko, MD; Chief Editor: Selim R Benbadis, MD  more...
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A seizure is an abnormal paroxysmal discharge of cerebral neurons due to cortical hyperexcitability. The new International Classification of Seizures divides seizures into 3 categories: generalized onset, focal onset (formerly partial seizures) and unknown onset. [8] This article uses the term "partial seizures" throughout although the term focal is now the official term. However, many patients and practitioners are using old terminology.

Partial seizures result from a seizure discharge within a particular brain region or focus, and they manifest focal symptoms and may progress to secondarily generalized seizure (now called bilateral tonic clonic, with the term generalization reserved for primary generalized seizure only). [8] Primary generalized seizures probably begin in the thalamus and other subcortical structures, but on scalp electroencephalographic (EEG) recordings, they may appear to start simultaneously in both cerebral hemispheres; therefore, they manifest symptoms bilaterally in the body and are always associated with loss of consciousness.

Partial seizures can generalize secondarily and result in tonic-clonic activity. Some partial seizures have very rapid generalization, and the partial phase of the seizure may not be readily apparent clinically or even on scalp EEG recordings. Some partial seizures may have an aura (the new classification discourages the use of aura and suggests the term simple focal seizure aware instead), but primary generalized seizures usually do not. However, secondarily generalized partial seizures (now called focal with bilateral tonic clonic in the new classification) are not included in the category of generalized seizures, which includes only primary generalized seizures.

Generalized seizures can be classified as atonic, tonic, clonic, tonic-clonic, myoclonic, or absence on the basis of clinical symptoms and EEG abnormalities. Tonic seizure is the rigid contracture of muscles, including respiratory muscles, which is usually brief. The clonic component is the rhythmic shaking that occurs and is longer. Together, a generalized tonic-clonic seizure (GTCS) is also called a grand mal seizure and is one of the most dramatic of all medical conditions.

The following epilepsy syndromes may have generalized seizures:

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. The awake EEG of patients with generalized tonic-clonic seizure may be normal; however, certain specific interictal EEG patterns can be distinctive of generalized epilepsy syndromes (see Workup). In generalized seizure patients, the activation of photic stimulation and/or hyperventilation during an EEG may produce spikes or even seizures.

A number of medications are used for the treatment of generalized tonic-clonic seizures. The choice of drug should be tailored to the individual patient and to the epilepsy syndrome, not only to the seizure type (see Treatment and Management, as well as Medication).

Go to Epilepsy and Seizures, First Adult Seizure, and First Pediatric Seizure for an overview of these topics.



Generalized epilepsy is thought to be initiated by 3 different mechanisms:

  • Abnormal response of hyperexcitable cortex to initially normal thalamic input

  • Primary subcortical trigger

  • Abnormal cortical innervation from subcortical structures

Physiologically, a seizure results from a paroxysmal high-voltage electrical discharge of susceptible neurons within an epileptogenic focus. These neurons are known to be hyperexcitable and, for unknown reasons, remain in a state of partial depolarization.

The neurons surrounding the epileptogenic focus are GABA-ergic (ie, they release gamma-aminobutyric acid) and hyperpolarized, and they inhibit the epileptogenic neurons. At times, when the epileptogenic neurons overcome the surrounding inhibitory influence, the seizure discharge spreads to neighboring cortical structures and then to subcortical and brainstem structures.

Various animal models of generalized epilepsy implicate brainstem structures in the pathogenesis of generalized seizures. These brainstem structures include the following:

  • A lateral geniculate body, which produces a generalized tonic-clonic seizure when kindled in the cat

  • Ascending pathways through the mamillary bodies and anterior thalamus

  • The substantia nigra, including a nigrotectal GABA-ergic projection and locus ceruleus

The spread of excitability to subcortical, thalamic, brainstem, and spinal cord structures corresponds with the tonic phase of the seizure. Following this, an inhibitory impulse starts from the thalamus and interrupts the tonic phase into discontinuous bursts of electrical activity, known as the clonic phase.



Most generalized epilepsies are idiopathic. However, a definite genetic locus has been found for some of these generalized types of epilepsy.

Benign familial neonatal convulsion is an autosomal dominant condition with high penetrance, resulting from mutations in a voltage-gated potassium channel gene, named KCNQ2, in chromosome 20. This gene is homologous to a gene (ie, KCNQ1) expressed in the heart, mutations of which are responsible for one form of the long QT syndrome. A channelopathy in the sodium channel b1 subunit (SCN1B) is associated with generalized epilepsy with febrile convulsions.

Unverricht-Lundborg disease, a progressive myoclonic epilepsy, is an autosomal recessive inherited disorder linked to chromosome arm 21q. The specific gene was identified recently as cystatin B, an intracellular protease inhibitor. For most of the other syndromes considered idiopathic generalized epilepsies, more than one gene is thought to be responsible.



The age-adjusted incidence of epilepsy (ie, recurrent unprovoked seizures) ranges from 24-53 per 100,000 population per year. Approximately 20-25% of cases are classified as generalized seizures. The age-adjusted prevalence of epilepsy ranges from 4-8 per 1000 people.

Developing countries have similar incidences of epilepsy, ranging from 14-57 cases per 1000 population, based on World Health Organization statistics. Internationally, as in the United States, partial seizures are the most common, but generalized tonic-clonic seizures still make up a significant percentage of seizures (20-25%).

Generalized convulsive seizures are uncommon in infants and rare in neonates. In elderly patients, generalized tonic-clonic seizures are usually due to secondary generalization of seizures emanating from localized brain lesions.



The morbidity for tonic-clonic seizure can be high because these patients experience no aura and thus the seizure strikes without warning; minor injuries are frequent. Patients can have posterior shoulder dislocations and broken bones.

Potential complications of generalized tonic-clonic seizures include the following:

  • Head trauma and trauma to the tongue, lips, and cheeks

  • Vertebral compression fractures

  • Aspiration pneumonia

  • Neurogenic pulmonary edema

  • Cardiac arrhythmias

  • Sudden death

Mortality rates for seizures are low, but, amongst the epilepsies, rates for tonic-clonic seizures are higher. The incidence of sudden death is 24 times higher in persons with epilepsy than in the general population. Some of the risk factors for sudden death in epilepsy (SUDEP) include high seizure frequency (specifically tonic-clonic type), younger age, mental retardation, and polytherapy. [1]


Patient Education

For patient education information, see the Brain and Nervous System Center, as well as Epilepsy.