Generalized onset tonic-clonic seizures

C P Panayiotopoulos MD PhD (Dr. Panayiotopoulos of St. Thomas' Hospital has no relevant financial relationships to disclose.)
Jerome Engel Jr MD PhD, editor. (Dr. Engel of the David Geffen School of Medicine at the University of California, Los Angeles, has no relevant financial relationships to disclose.)
Originally released February 26, 2013; last updated March 23, 2020; expires March 23, 2023

This article includes discussion of generalized onset tonic-clonic seizures, grand mal seizures, primarily generalized tonic-clonic seizures, primary generalized tonic-clonic seizures, and bilateral tonic-clonic seizures. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.


Generalized onset tonic-clonic seizures are the most dramatic, severe, and common seizures of mainly syndromes of idiopathic generalized epilepsy. They manifest with violent generalized convulsions, loss of consciousness, and marked autonomic disturbances. They are usually spontaneous, but they may also be provoked by external, mainly photic, stimuli. They occur at any time, but mainly on awakening. They are often associated with severe complications that may also be fatal. They affect patients of all ages, except neonates. Additionally, patients may also suffer from other types of seizures, such as absences and myoclonic jerks. Syncope and psychogenic nonepileptic seizures are frequently misdiagnosed as generalized onset tonic-clonic seizures. Treatment is demanding because a significant number of currently available antiepileptic drugs may aggravate generalized seizures. In this updated article, the author details the clinical manifestations, pathophysiology, EEG, and neuroimaging of generalized onset tonic-clonic seizures and provides clues for correct diagnosis and optimal management of patients.

Key points


• Generalized onset tonic-clonic seizures are the most severe type of epileptic seizure, and significant complications often occur.


• They manifest with a tonic-clonic sequence of violent convulsions, loss of consciousness, and marked autonomic disturbances.


• Generalized onset tonic-clonic seizures occur in idiopathic generalized epilepsies such as epilepsy with generalized tonic-clonic seizures alone and juvenile myoclonic epilepsy.


• Seizures may be precipitated by photic stimuli and facilitated by sleep deprivation, fatigue, and excessive alcohol consumption.


• The required treatment is mainly with valproate, levetiracetam, and lamotrigine as a monotherapy or polytherapy.


• Syncope and psychogenic non-epileptic seizures are frequently mistaken as generalized onset tonic-clonic seizures.

Historical note and terminology

Historical aspects. The manifestations of GTCS are so dramatic that accurate descriptions can be found as early as 1050 BC in the twenty-fifth Babylonian cuneiform tablet devoted to miqtu (a disease in which the person loses consciousness and foams at the mouth) (Bladin and Eadie 2010). A realistic depiction of GTCS, including marked cyanosis, can be seen in the painting The Miracles of St Ignatius of Loyola (1617) by Peter Paul Rubens (1577-1640) (Wolf 2010).

Gowers gives an excellent description of GTCS (Gowers 1880):


At the onset of the severe fit the spasm is tonic in character, – rigid, violent, muscular contraction, fixing the limbs in some strained position… When the cyanosis has become intense, the fixed tetanic contractions of the muscles can be felt to be vibratory, and the vibrations gradually increase until there are slight visible remissions. As these become deeper, the muscular contractions become more shock-like in character… Such attacks may commence with tonic spasm, or they may commence by, and sometimes consist only of clonic spasm… Precursory symptoms occasionally precede a fit, sudden jerks of the body or limbs.

However, it was Henri Gastaut and his associates in Marseilles, France who provided us with superb descriptions of the clinical and EEG manifestations of GTCS, which have not been surpassed (Gastaut and Broughton 1972). Their description was based on a large number of combined clinical, EEG, and polygraphic investigations of GTCS in patients with epileptic disorders or induced by Metrazol or electroconvulsive treatment of psychotic patients. These were supplemented by cinematographic or videotaped filming and various other techniques. Contributions have been made with video-EEG analysis (Niaz et al 1999; Casaubon et al 2003).

ILAE classification and nomenclature. A fundamental distinction of all ILAE classifications is whether tonic-clonic seizures are of generalized or focal onset (Engel 2001; Engel 2006; Berg et al 2010; Commission on Classification and Terminology of the International League Against Epilepsy 2014; Fisher et al 2017a; Fisher et al 2017b).

According to the ILAE definitions, generalized seizures “originate at some point within, and rapidly engage, bilaterally distributed networks. Such bilateral networks can include cortical and subcortical structures, but do not necessarily include the entire cortex. Although individual seizure onsets can appear localized, the location and lateralization are not consistent from one seizure to another. Generalized seizures can be asymmetric.” Conversely, focal seizures “originate within networks limited to one hemisphere, which may be discretely localized or more widely distributed. Focal seizures may originate in subcortical structures” (Berg et al 2010; Commission on Classification and Terminology of the International League Against Epilepsy 2014; Fisher et al 2017a; Fisher et al 2017b).

The ILAE description of GTCS in the 1981 proposal is as follows (Commission on Classification and Terminology of the International League Against Epilepsy 1981):


The most frequently encountered of the seizures are GTCS, often known as grand mal. Some patients experience a vague ill-described warning, but the majority lose consciousness without any premonitory symptoms. There is a sudden, sharp tonic contraction of muscles, and when this involves the respiratory muscles, there is stridor, a cry or moan, and the patient falls to the ground in the tonic state, occasionally injuring him or herself. The patient lies rigid, and during this stage, tonic contraction inhibits respiration and cyanosis may occur. The tongue may be bitten and urine may be passed involuntarily. This tonic stage then gives way to clonic convulsive movements lasting for a variable period of time. During this stage, small gusts of grunting respiration may occur between the convulsive movements, but usually the patient remains cyanotic and saliva may froth from the mouth. At the end of this stage, deep respiration occurs and all the muscles relax, after which the patient remains unconscious for a variable period of time and often awakes feeling stiff and sore all over. He or she then frequently goes into a deep sleep and when awakened feels quite well apart from soreness and, frequently, headache. GTCS may occur in childhood and in adult life; they are not as frequent as absence seizures, but vary from one day to one every 3 months and occasionally to one every few years. Very short attacks without postictal drowsiness may occur on occasion.

GTCS are defined as follows in the ILAE glossary (Blume et al 2001):


Generalized tonic-clonic seizure (synonym: bilateral tonic-clonic seizure--formerly “grand mal” seizure, noun): bilateral symmetrical tonic contraction, then bilateral clonic contractions of somatic muscles usually associated with autonomic phenomena.

Note that the terms “primarily” and “secondarily” GTCS should not be confused with the now obsolete terms of “primary” and “secondary epilepsy,” which have been rightly abandoned by the ILAE and by most physicians, though they are often used in formal reports of antiepileptic drug trials. Additionally, these terms are not used in the current ILAE glossary (Blume et al 2001). Furthermore, “primarily” and “secondarily” GTCS have been abolished in the new ILAE definitions and “secondarily generalized tonic-clonic” has been replaced by “focal to bilateral tonic-clonic” (Fisher et al 2017a; Fisher et al 2017b).

In the 2014 ILAE “Epilepsy diagnosis” manual, generalized onset tonic-clonic seizures are categorized amongst generalized convulsive seizures (Commission on Classification and Terminology of the International League Against Epilepsy 2014). Generalized seizures are convulsive, absence, tonic, atonic, and myoclonic.


“Generalized convulsive seizures are typically bilateral and symmetric although variants with asymmetry including head and eye deviation can be seen. A tonic clonic seizure is a seizure consisting of a tonic and a clonic phase, typically in this order, however variations such as clonic-tonic-clonic are also seen. A clonic seizure is a seizure involving bilaterally rhythmic jerking and may occur alone or in combination with tonic activity where there is bilaterally increased tone of the limbs typically lasting seconds to a minute. The jerking in a clonic seizure is more sustained and rhythmic than seen in a myoclonic seizure” (Commission on Classification and Terminology of the International League Against Epilepsy 2014).

The most recent ILAE positional papers on the operational classification of seizure types retain the name “generalized onset tonic-clonic seizures” and classifies them amongst “generalized onset motor seizures” (Fisher et al 2017a; Fisher et al 2017b). Generalized onset seizures are motor (tonic-clonic, clonic, tonic, myoclonic, myoclonic-tonic-clonic, myoclonic-atonic, atonic, epileptic spasms) or nonmotor (absence) (typical, atypical, myoclonic, eyelid myoclonia). GTCS are defined as follows (Fisher et al 2017a; Fisher et al 2017b):


“bilateral symmetric or sometimes asymmetric tonic contraction and then bilateral clonic contraction of somatic muscles, usually associated with autonomic phenomena and loss of awareness. These seizures engage networks in both hemispheres at the start of the seizure. Generalized myoclonic-tonic-clonic seizures begin with a few myoclonic jerks followed by tonic-clonic activity. These seizures are commonly seen in patients with juvenile myoclonic epilepsy and occasionally with other generalized epilepsies. It is arguable whether the initial jerks are myoclonic or clonic, but they are rarely sufficiently sustained to be considered clonic. Because there is a new seizure type (myoclonic-tonic-clonic) characterized by myoclonic movements preceding tonic (stiffening) and clonic (sustained rhythmic jerking) movements, it is important to document the early movements of a tonic-clonic seizure as being tonic. The clonic phase of a tonic-clonic seizure typically shows regularly decreasing frequency of jerks over the course of the event. During a tonic-clonic seizure, awareness is lost before or contemporaneously with the stiffening and jerking movements. Some tonic-clonic seizures may invoke a nonspecific feeling of an impending seizure or a brief period of head or limb version, neither of which invalidates a generalized onset, since biologic processes never exhibit perfect synchrony. The clinician has to judge whether a truly focal onset is present.”

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