eMedicine Specialties > Neurology > Seizures and Epilepsy

Generalized Tonic-Clonic Seizures

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

Introduction

Background

A seizure is an abnormal paroxysmal discharge of cerebral neurons due to cortical hyperexcitability. The International Classification of Seizures divides seizures into 2 categories: partial seizures (ie, focal or localization-related seizures) and generalized seizures.

Partial seizures result from a seizure discharge within a particular brain region or focus, and they manifest focal symptoms. Generalized seizures probably begin in the thalamus and other subcortical structures, but on scalp 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. However, secondarily generalized partial seizures are not included in the category of generalized seizures, which includes only primary generalized seizures.

Generalized convulsive 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.

Several epilepsy syndromes have generalized seizures: benign neonatal convulsions, benign myoclonic epilepsy of infancy, childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy, and generalized tonic-clonic seizures upon awakening.

Pathophysiology

Generalized epilepsy is thought to be initiated by 3 different mechanisms: (1) abnormal response of hyperexcitable cortex to initially normal thalamic input, (2) primary subcortical trigger, and (3) 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 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 (1) a lateral geniculate body, which produces a generalized tonic-clonic seizure when kindled in the cat; (2) ascending pathways through the mamillary bodies and anterior thalamus; and (3) 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.

Frequency

United States

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

International

Developing countries have similar incidences of epilepsy, ranging from 14-57 per 1000 people, based on World Health Organization statistics. Internationally, as in the United States, only a small proportion of seizures are generalized tonic-clonic seizures (20-25%); the majority are partial seizures.

Mortality/Morbidity

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

Age

• 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.

Clinical

History

• Prodromal symptoms
  • Patients with generalized tonic-clonic seizures may report having a prodrome, which comprises premonitory symptoms occurring hours or days before a seizure. Common prodromes include mood changes, sleep disturbances, lightheadedness, anxiety, irritability, difficulty concentrating and, rarely, an ecstatic feeling. Patients with generalized tonic-clonic seizures do not have auras. An aura represents a simple partial seizure, and a reliable history of aura identifies the seizure as partial and not generalized.
  • Other symptoms that have been described less consistently are abdominal pain, facial pallor, or headache. Most patients lose consciousness without any premonitory symptoms.

Physical

The patient may have completely nonfocal findings on neurologic examination when not having seizures. Seizures typically are divided into tonic, clonic, and postictal phases, which are described in detail in this section.

• Tonic phase
  • Generalized convulsive seizures may begin with myoclonic jerks or, rarely, with absences. The tonic phase begins with flexion of the trunk and elevation and abduction of the elbows. Subsequent extension of the back and neck is followed by extension of arms and legs. This can be accompanied by apnea, which is secondary to laryngeal spasm.
  • Autonomic signs are common during this phase and include increase in pulse rate and blood pressure, profuse sweating, and tracheobronchial hypersecretion.
  • Although urinary bladder pressure rises, voiding does not occur because of sphincter muscle contraction.
  • This stage lasts for 10-20 seconds.
• Clonic phase
  • The tonic stage gives way to clonic convulsive movements, in which the tonic muscles relax intermittently, lasting for a variable period of time.
  • During the clonic stage, a generalized tremor occurs at a rate of 8 tremors per second, which may slow down to about 4 tremors per second. This is because phases of atonia alternate with repeated violent flexor spasms. Each spasm is accompanied by pupillary contraction and dilation. Some patients may have tongue or cheek bites.
  • The atonic periods gradually become longer until the last spasm. Voiding may occur at the end of the clonic phase as sphincter muscles relax. The atonic period lasts about 30 seconds. The patient continues to be apneic during this phase.
  • The convulsion, including tonic and clonic phases, lasts for 1-2 minutes.
• Postictal state
  • The postictal state includes a variable period of unconsciousness during which the patient becomes quiet and breathing resumes.
  • The patient gradually awakens, often after a period of stupor or sleep, and often is confused, with some automatic behavior.
  • Headache and muscular pain are common. The patient does not recall the seizure itself.

Causes

• Most generalized epilepsies are idiopathic, but a definite genetic locus has been found for some of these generalized types of epilepsy.
• Benign familial neonatal convulsion is an autosomal dominant inherited condition with high penetrance, resulting from mutations in a voltage-gated potassium channel named KCNQ2 in chromosome 20. This gene is homologous to a gene (ie, KCNQ1) expressed in the heart, where mutations 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.

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