Tonic Clonic Seizure

GTC seizures consist of a sudden loss of consciousness, a tonic phase of intense muscle contraction and then a clonic phasic consisting of bilaterally synchronous jerking of the entire body.

From: Sleep Medicine Pearls (Third Edition) , 2015

Tonic–Clonic Seizures☆

N. Hammond , in Reference Module in Biomedical Sciences, 2016

Abstract

Tonic–clonic seizures can result from either primary or secondary generalized seizures. Tonic–clonic seizures are characterized by clonic or myoclonic movements evolving to tonic muscle extension of the limb and trunk muscles followed by clonic contraction. Often these seizures are accompanied by biting of the tongue and urinary incontinence. Tonic–clonic seizures may be accompanied by significant morbidity and mortality. Brain injury and malformations, genetic disorders, inborn errors of metabolism and neurodegenerative disorders may be associated with tonic–clonic seizures. The pathogenesis of tonic–clonic seizures is not fully elucidated but probably involves widespread networks in the brain. Treatment choices for tonic–clonic seizures include medication and non-medication options.

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NEUROTRANSMITTER FUNCTION | Role of Noradrenergic System in Seizure Regulation

R.A. Browning , P.C. Jobe , in Encyclopedia of Basic Epilepsy Research, 2009

Human Studies

Generalized tonic–clonic seizures (grand mal) are essentially brainstem-driven convulsive seizures in humans. Antidepressants that inhibit NE reuptake are anticonvulsant against tonic–clonic seizures in humans. This effect is expected, given the data showing that NE is so dramatically effective against tonic extension in both the maximal electroshock and in tonic–clonic seizures in GEPRs. Since many of these tonic–clonic seizures are secondarily generalized, it is expected that the effects of NE on forebrain seizures (e.g., temporal lobe seizures), as described earlier, would also suppress the transition from limbic/cortical to brainstem seizures and be beneficial in suppressing tonic–clonic seizures. In fact, there is evidence that monoamine enhancing antidepressants can suppress seizures in patients with secondarily generalized convulsive seizures.

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Drug- and Toxin-Associated Seizures

Brandon Wills , ... John P. Ney , in Clinical Neurotoxicology, 2009

Neuroanatomy of Generalized Seizures

Generalized seizures have long been thought to involve diffuse activation of the cerebral cortex without preference for anatomical region. However, recent neuroimaging studies in two models of epilepsy suggest that generalized seizure activity selectively activates some areas of the cortex, as well as areas of the subcortex, while sparing others during the ictal event. By tracking elevations in cerebral blood flow (CBF) markers via single-photon emission computed tomography (SPECT) and oxygenation levels in functional magnetic resonance imaging, the neuroanatomical networks involved in generalized seizure activity are being elucidated.

The use of ECT for the treatment of refractory depression has provided a human model for neuronal activation in generalized seizure activity. Bifrontal or bitemporal ECT induces generalized seizure activity in a controlled setting, allowing for SPECT imaging. Increases in CBF indicate increased metabolism through aberrant activation of neurons. 35 Tracking CBF with xenon or technetium markers during a bitemporal ECT-induced generalized seizure reveals focal hyperperfusion of frontal and temporal lobes, as well as distal parietal regions, with no changes to CBF in areas of intervening cortex. Subcortical regions, including the medial thalamus, and brainstem tegmentum also have increased CBF during ECT, suggesting that subcortical networks are involved in seizure propagation to distant cortex. 36

Experimental models of generalized tonic–clonic seizures with rats using the GABA antagonist pentylenetetrazole (PTZ) also reveal neuroanatomical areas of focal activation. Using functional magnetic resonance imaging to image blood oxygen level–dependent signal intensity is an indicator of hypermetabolism and thus neuronal firing. The anterior thalamus, dentate gyrus of the hippocampus, and posterior midline retrosplenial cortex all show at least a twofold greater response to PTZ relative to other areas of the cerebrum in times just preceding and during generalized seizure activity. 37 These experiments again suggest that "generalized" seizures, likely including DTSs, are mediated by discrete cortical and subcortical regions.

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Tonic-Clonic (Grand Mal) Seizures

Arun Angelo Patil , in xPharm: The Comprehensive Pharmacology Reference, 2007

Consequences

Tonic-clonic seizures can be fatal. Death can occur as a result of a fall during the seizure or some other type of accident, such as drowning. Patients may also die during a tonic-clonic seizure without an obvious cause. This is called "sudden unexpected death from epilepsy (SUDEP)" Walczak et al (2001). Although the precise cause of death is unknown, it may be due to cardiac arrhythmias, pulmonary edema, suffocation, or severe generalized suppression of brain function. Death may also occur if a tonic-clonic seizure, which is usually self-limiting, progresses to uncontrolled status epilepticus.

Patients can also become encephalopathic as a result of seizure-induced damage to the brain. This can lead to mental retardation in children.

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Epilepsy

Nancy Foldvary‐Schaefer , Elaine Wyllie , in Textbook of Clinical Neurology (Third Edition), 2007

Tonic‐Clonic Seizures

Tonic‐clonic seizures (TCS) are the most common type of seizure encountered in childhood, adolescence, and adulthood. The manifestations of generalized TCS can be divided into several phases beginning with vague prodromal symptoms that may occur hours to days before the actual convulsion. Common premonitory symptoms include headache, mood change, anxiety, irritability, lethargy, changes in appetite, dizziness, and lightheadedness. The tonic phase may be preceded by a series of brief, bilateral muscle contractions lasting a few seconds. The tonic phase begins with brief flexion of the trunk, accompanied by upward deviation of the eyes, mydriasis, and a characteristic vocalization as contraction of abdominal muscles produces forced expiration across a spasmodic glottis. This process is followed by a period of generalized extension lasting 10 to 15 seconds. With evolution of the clonic phase, tonic contractions alternate with periods of muscle atonia of gradually increasing duration until contractions cease. The seizure terminates with a final generalized tonic spasm. Loss of consciousness and autonomic alterations occur during the tonic and clonic phases. Secondarily, generalized seizures may be preceded by focal or lateralized clinical behaviors such as involuntary jerking of an extremity or head version before the onset of bilateral motor manifestations. Similarly, focal weakness of an extremity during the postictal state (Todd's paralysis) indicates seizure origin from the contralateral hemisphere. TCS commonly produce hypocarbia, owing to a combined respiratory alkalosis and lactic acidosis, transient hyperglycemia, mild cerebrospinal fluid (CSF) pleocytosis, and elevated serum prolactin. The immediate postictal state is characterized by coma that is gradually replaced by a confusional state. Once consciousness is regained, lethargy, myalgia, and headache are often reported. Most TCS are less than 1 minute in duration. Potential complications include oral and head trauma, vertebral body stress fractures, aspiration pneumonia, pulmonary edema, and death.

Generalized TCS occurring in patients with idiopathic generalized epilepsies are associated with normal background activity and bilaterally synchronous and symmetrical spikes, polyspikes, or spike‐wave complexes on the interictal EEG. Secondarily generalized TCS are usually associated with background abnormalities and focal or lateralized slowing and epileptiform activity. During the tonic phase of a TCS, generalized low‐amplitude 20‐ to 40‐Hz activity evolves into a bilaterally synchronous and symmetrical 10‐Hz rhythm, which is referred to as the epileptic recruiting rhythm. Generalized polyspikes interrupted by slow waves characterize the clonic phase. The postictal period is characterized by generalized suppression or low‐amplitude slow activity.

Experimental animal models using systemic chemoconvulsants and maximal electroshock provide some insight into the neuronal structures involved in the production of TCS. Lesions involving the pontine reticular formation produce the tonic phase in several animal models. Involvement of forebrain structures is required for the production of clonus, suggesting that an interaction of brain stem and neocortical structures takes place. These findings, however, have not been confirmed in humans.

TCS are observed in patients with idiopathic and symptomatic epilepsies and in association with systemic disease. 7 Hyponatremia, hypoglycemia, alcohol withdrawal, and drugs are common causes of isolated seizures particularly in hospitalized patients. Drugs that may precipitate TCS include tricyclic antidepressants, antipsychotics, anticholinergics, antihistamines, methylxanthines, antibiotics, and withdrawal from barbiturates and benzodiazepines. The prognosis for patients with idiopathic generalized TCS is better than that for those with focal or secondary generalized seizures (Video 74, Secondary Generalized Seizure), which tend to persist if untreated. The remission rate is greatest in patients who develop TCS in childhood in the absence of other seizure types.

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Disorders Affecting Feeding and Swallowing in Infants and Children

Pamela Dodrill , in Dysphagia (Second Edition), 2016

Generalized seizures are the result of abnormal activity in both hemispheres of the brain simultaneously. They all involve a loss of consciousness, and typically happen without warning. There are six main types of generalized seizures:

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Tonic seizures produce a sustained contraction of the muscles of the limbs followed by their extension, along with arching of the back. The individual often stops breathing during the seizure.

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Clonic seizures involve shaking of the limbs.

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Tonic-clonic seizures involve a tonic component followed by a clonic component.

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Myoclonic seizures involve spasms of muscle groups.

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Atonic seizures involve loss of muscle activity.

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Absence seizures are often subtle, with a minor activity, such as eye blinking or a turn of the neck.

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Epilepsy

Antonietta Coppola , Solomon L. Moshé , in Handbook of Clinical Neurology, 2012

Tonic–clonic seizures

Tonic–clonic seizures are generalized seizures consisting of tonic flexion and extension of forelimb, hindlimb, or both – longlasting clonus of all limbs with the animal unable to stand (Veliskova, 2006).

The origin of tonic seizures is not known; some investigators believe it to be in the brainstem structures (Browning, 1985). In most models, tonic–clonic seizures represent the spread of paroxysmal activity from the forebrain to the brainstem (Browning, 1985). However, few models show seizures with a primary origin in the brainstem structure, such as in maximal electroshock stimulation (MES) or in genetically prone animals such as genetically epilepsy-prone rats (GEPRs) (Ludvig and Moshé, 1989).

During early life, tonic–clonic seizures are readily elicited by most convulsants, but variability of the phases can be observed depending on the seizure model. In most models, tonic–clonic seizures can start with swimming-like movements. Rearing depends on the developmental stage of the rodent and is rarely seen before 15   days of age. The tonic phase consists of tonic flexion and extension of forelimbs and flexion of hindlimbs of variable duration. There may be periods of gasping and opisthotonus (de Feo et al., 1985; Velisek et al., 1992).

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MODELS | Models of Generalized Seizures in Freely Moving Animals

L. Velíšek , in Encyclopedia of Basic Epilepsy Research, 2009

Background

Primary generalized seizures – seizures that appear to arise simultaneously over broad regions of the brain – are very common in the human population. Examples of human primarily generalized seizures are absence seizures, generalized clonic seizures, and generalized tonic-clonic seizures. Animal research and improved diagnostic techniques (especially imaging) have recently led to the view that at least some of the seizures previously categorized as 'primary generalized' are actually of focal origin (e.g., in the somatosensory cortex), but spread rapidly (i.e., are actually secondarily generalized). Without question, however, primary generalized seizures constitute a significant proportion of the seizure types seen clinically. Models of generalized seizures in experimental animals contribute a great deal to understanding the mechanisms of seizure spread and control, and also to the search for better antiepileptic therapy; indeed, two generalized seizure models are used for routine testing of newly synthesized compounds (see earlier text). In addition, many epileptic syndromes of childhood involve primarily generalized seizures. Examples of these syndromes are early myoclonic encephalopathies (newborns), infantile spasms (age: 3–12   months), and Lennox-Gastaut syndrome (age: 1–8   years). While current animal models of generalized seizures correspond very well to human generalized clonic, tonic-clonic, and absence seizures, the satisfactory models for many childhood epileptic syndromes involving generalized seizures still do not exist. Recently, better models for infantile spasms have been developed (see Stafstrom and Velíšek), giving the field an opportunity to study underlying mechanisms and more effective therapeutic agents for this catastrophic seizure syndrome of childhood. However, there is a pressing need to develop models for other catastrophic seizure syndromes (associated with progressive mental retardation and, frequently, death) in order to improve current therapy. Appropriate and accurate animal models can provide insights into pathogenesis of these syndromes, and lay the foundation for future mechanistic treatments.

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Epilepsy

Tiziana Granata , in Handbook of Clinical Neurology, 2012

Epilepsy with generalized seizures

Generalized seizures may include atypical absences, massive myoclonic seizures, and akinetic seizures; tonic seizures are rarely observed. The differential diagnosis from idiopathic generalized epilepsy rests on the "unusual" association of different types of seizure in an individual patient (e.g., the association of focal and generalized seizures, or the lack of tonic seizures during sleep in epilepsy resembling Lennox–Gastaut syndrome), on the frequent occurrence of stimulus-induced (light, noise) seizures, and on the EEG characteristics. EEG may show impaired background activity or sleep organization, unusual fast or rhythmic activity, association of focal and generalized epileptic abnormalities, and photic-induced epileptic discharges at low stimulus frequency (Figs 30.4–30.6).

Fig. 30.4. Electroencephalogram recording in a patient aged 8   months affected by peroxisomal disease in whom brief spontaneous myoclonic seizure occurred spontaneously (A) or following intermittent light stimulation (ILS) at low frequency (C). Nonepileptic startles, induced by unexpected stimuli, were also present (B). Sleep recording showed multifocal interictal epileptic discharges (D).

Fig. 30.5. Electroencephalogram (EEG) recording in a patient aged 7   years affected by a mitochondrial encephalopathy due to a defect in complex IV of the respiratory chain. The interictal EEG shows multifocal epileptic discharge abnormalities (A and B). Intermittent light stimulation induces massive myoclonia associated with a diffuse discharge of irregular spikes and waves (C, arrow), followed by periodic sharp waves higher on the posterior regions. Subtle myoclonic jerks are recorded from distal muscles.

Fig. 30.6. Electroencephalogram recording in a patient aged 5   years affected by late infantile lipofuscinosis. (A) Recording of an atypical absence, associated with a diffuse discharge of irregular spikes and waves. (B) Low-frequency intermittent light stimulation (ILS) elicits a discharge of irregular spikes and waves more evident on the posterior regions. (C) Continuous irregular spikes and waves during sleep.

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Models of Generalized Seizures in Freely Moving Animals☆

L. Velíšek , in Reference Module in Neuroscience and Biobehavioral Psychology, 2017

Background

Primary generalized seizures – seizures that appear to arise simultaneously over broad regions of the brain – are common in the human population. Examples of human primarily generalized seizures are absence seizures, generalized clonic seizures, bilateral myoclonic seizures, atonic seizures, and generalized tonic-clonic seizures. Animal research and improved diagnostic techniques (especially imaging) have recently led to the view that at least some of the seizures previously categorized as "primary generalized" are actually of focal origin (eg, in the somatosensory cortex), but spread rapidly (ie, are actually secondarily generalized). Without question, however, primary generalized seizures constitute a significant proportion of the seizure types seen clinically. Models of generalized seizures in experimental animals contribute a great deal to understanding the mechanisms of seizure spread and control, and also to the search for better antiepileptic therapy; indeed, two generalized seizure models are used for routine testing of newly synthesized compounds (see earlier text). In addition, many epileptic syndromes of childhood involve primarily generalized seizures. Examples of these syndromes are early myoclonic encephalopathies (newborns), infantile spasms (age: 3–12 months), and Lennox-Gastaut syndrome (onset age: 3–6 years). While current animal models of generalized seizures correspond very well to human generalized clonic, tonic-clonic, and absence seizures, the satisfactory models for many childhood epileptic syndromes involving generalized seizures still do not exist or are under development. Recently, better models for infantile (epileptic) spasms have been developed, giving the field an opportunity to study underlying mechanisms and more effective therapeutic agents for this devastating seizure syndrome of childhood. However, there is a pressing need to develop models for other seizure syndromes with devastating consequences (frequently associated with progressive arrest of development, autism, and, frequently, death) in order to improve current therapy. Appropriate and accurate animal models can provide insights into pathogenesis of these syndromes, and lay the foundation for future mechanistic treatments of true anti-epileptic drugs.

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