Generalized tonic seizures are convulsive events in which the tonic component is predominant and not followed by clonic jerks. Actually, the majority of convulsive generalized seizures have both tonic and clonic components, especially in generalized epilepsies. Also, in partial epilepsy a secondary generalized seizure usually manifests a clonic phase.⁵³ On the basis of experimental animal models of epilepsy, there is evidence that different circuits are responsible for tonic and clonic seizures and indicate that the anatomic substrate for tonic seizures could be in the brainstem.⁵⁸ Possibly due to their intrinsic pathophysiology, which heavily involves the brainstem, tonic seizures are a common manifestation in pediatric age and especially in symptomatic/lesional epilepsies, in which a forebrain/brainstem dysfunction could be more easily hypothesized. In the neonatal period tonic seizures are recorded in early infantile epileptic encephalopathy (EIEE), in early myoclonic encephalopathy (EME) (see Chapters 224 and 225), and in severe symptomatic neonatal seizures, especially those due to hypoxic-ischemic perinatal injury, which account for 50% of such seizures.² During infancy, tonic seizures are observed in refractory infantile spasms, especially after the first year of life and are sometimes associated with epileptic spasms (tonic-spasm epileptic seizure).¹⁴ Tonic seizures are the main seizure type in symptomatic generalized epilepsy associated with an inverted duplication of chromosome 15⁴⁹ and in Lennox-Gastaut syndrome.³ Among the partial epilepsies, tonic events are the main type of seizures recorded in startle-induced epilepsy, in which the tonic seizure is often generalized, despite the focality of the underlying lesion. Although rare, there are also reports of tonic seizures belonging to idiopathic generalized epilepsies³² and in this case they follow the same course as generalized tonic–clonic seizures.

Tonic seizures are classified among the generalized seizures and described as follows: “a rigid, violent muscular contraction, fixing the limbs in some strained position, with usually deviation of the eyes and of the head toward one side.” Thus, we consider a seizure as purely tonic when the hypertonia, mainly involving the axial muscles, is not followed by clonic jerks. This is independent of the symmetry or the extention nature of the contraction.

The glossary of descriptive terminology for ictal semeiology describes, among the generalized events, the tonic seizure as “a sustained increase in muscle contraction lasting a few seconds to minutes.”¹⁰

On the basis of a single case, Jackson and Barnes²⁸ and Jackson and Singer²⁹ accurately described tonic seizures as “the axial type,” which were considered immature grand mal seizures. Lennox³⁵ described tonic seizures as convulsive variants, involving brief muscle rigidity without subsequent clonus. Detailed clinicoelectroencephalographic studies of tonic seizures were later conducted by Ouachi et al.⁴³ and Gastaut et al.,²² mainly on the tonic seizures of Lennox-Gastaut syndrome. A clear distinction between tonic and tonic–clonic seizures was made. Following these studies, tonic seizures were classified as a separate type of generalized epileptic attack.^7,18 However, the tonic seizure may also be a clinical manifestation of localization-related epilepsies, especially of those originating from frontal lobe areas.¹¹

From a clinical point of view, and especially where only historical information is available, it is not always easy to distinguish clearly between pure tonic and tonic–clonic seizures. Unfortunately, the distinction between the two types of seizure are not always clear in the literature as well.

Epidemiologic data about tonic seizures are difficult to identify outside the context of the epileptic syndrome in which they occur. However, in recent years more attention has been given to the epidemiology of each epileptic syndrome, and some data about the prevalence of Lennox-Gastaut syndrome, refractory infantile spasms, EIEE, and focal epilepsies are now available.^32,34,54 In the population-based study conducted using a multiple-source surveillance system for epilepsy and developmental disability by Trevathan et al.,⁵⁴ the prevalence among Atlanta children of Lennox-Gastaut syndrome was 4% of all children with epilepsy. In the study reported by Kramer et al.,³² the relative frequency and age of onset of the different seizure types were analyzed in a 20-year cohort of a pediatric neurology outpatient clinic in Tel Aviv. Lennox-Gastaut syndrome accounted for 1.5%, EIEE for 0.2%, and generalized tonic seizures not otherwise specified for 6.6%. In a subsequent study by Kwong et al.³⁴ performed in a cohort of 309 Chinese children, Lennox-Gastaut syndrome prevalence was 3%, but the prevalence of tonic seizures was not specified separately.

Previously, data regarding only Lennox-Gastaut syndrome showed that tonic seizures, as reported in papers by Gastaut et al.²⁰ and other authors,^6,39 were experienced in 55% to 60% of cases. Gastaut et al.²³ reported that such a percentage probably underestimates the real incidence of tonic seizures in Lennox-Gastaut syndrome, as the incidence of tonic seizures rises to 92% at the Centre Saint-Paul, a specialized institution in which the patients are under constant observation and are usually recorded during sleep.

More difficult to estimate is the prevalence of reflex tonic seizures in startle-induced epilepsy. The papers on tonic reflex seizures come mainly from laboratories specializing in the surgical treatment of medically resistant lesional startle-induced epilepsies, which, therefore, have limited epidemiologic value. Kramer et al.³² reported that startle-induced epilepsy in their cohort accounted for 0.2% of cases.

There is relative agreement on the brainstem involvement or origin of tonic seizures, both in Lennox-Gastaut syndrome and in EIEE or EME, whereas a cortical circuit is presumed to be involved in tonic seizures of startle-induced epilepsy. In animal models, the tonic extensor convulsion is the characteristic motor pattern of seizures evoked by maximal electroshock and high doses of chemoconvulsants.¹⁶ As demonstrated by Tanaka and Mishima⁵⁰ and later by Browning and Nelson,⁵ in animal models a tonic convulsion requires the integrity of the brainstem but not the forebrain. However, the anatomic substrates within the brainstem responsible for generating tonic seizures have not fully been characterized. The reticular formation of the lower midbrain and pons are surely involved, as stimulation of these regions triggers tonic convulsions, and a lesion can attenuate them.¹⁷ As a result of these experiments and the similarity between clinical tonic seizures and those induced in animals, a role for the brainstem in the initiation of convulsive seizures has long been suspected. However, as pointed out by Velasco and Velasco,⁵⁶ the literature on the role of the brainstem in the initiation and propagation of seizure activity is very contradictory. Velasco et al.⁵⁷ recorded ictal discharges of various types of generalized seizures within the centromedian thalamic nucleus (CM) and the cerebral cortex in children with intractable generalized seizures related to Lennox-Gastaut syndrome. Ictal CM discharges were consistently correlated with widespread surface cortical electroencephalographic (EEG) activities and symptoms in all patients and all types of generalized seizures. Fast spike discharges in the CM correlated with onset of tonic and tonic–clonic generalized seizures. Ictal EEG activity occurred simultaneously in the right and left CM and the surface at the onset of all seizure types of a generalized nature, with the exception of myoclonic seizure. Velasco et al.⁵⁷ maintain that simultaneous thalamic and cortical activation depends on epileptic discharges arising from cerebral structures outside the thalamocortical system. They postulate that the presence of abnormalities in the brainstem close to the red nucleus noted in MRI scans of all children with Lennox-Gastaut syndrome imply that epileptic discharges may arise from the brainstem.⁵⁵ The fact that tonic seizures occur more frequently during slow-wave sleep than during rapid eye movement (REM) sleep, modify sleep organization,^27,45,62 and raise the level of vigilance³⁶ also support the hypothesis that tonic seizures originate in the brainstem. Recently Veliskova et al.⁵⁸ provided evidence from animal studies that the anatomic substrate for tonic seizure could be in the brainstem, suggesting that different circuits are responsible for tonic and clonic seizures. In a previous animal study, excitation of the brainstem reticular formation produced convulsive seizures in decerebrated rats and cats, demonstrating that reticular neuronal circuits are independent of cortical networks in seizure generation.³³ Rodin et al.⁴⁷ used Metrazol and Megimide to produce seizures. He hypothesized that different functional states of the animal were a significant variable in the distribution of seizure activity. In paralyzed and unanesthetized animals, epileptic discharges were evident in the thalamus and cortex, whereas they were mainly in the brainstem reticular formation in freely moving animal.

A cortical origin for tonic reflex seizures seems to be likely, based on neuroimaging and neurophysiologic studies performed in surgery centers. Such data support involvement of the supplementary motor area in generation of this seizure type.^38,40 Gates et al.^25,26 and Courtney et al.⁸ described the effectiveness of corpus callosotomy in patients with refractory tonic seizures. Disappearance of reflex tonic seizures after callosal section (which prevents the spread from one unilateral focus to the contralateral homotopic motor center) is not completely unexpected. More difficult to explain is how seizures believed to originate from brainstem structures are improved by a callosal section. Though there is both, speculation²⁶ and controversy²⁴ concerning the efficacy of corpus callosotomy in controlling generalized tonic seizures, clinical and experimental evidence currently available indicates that seizure activity can spread and generalize in humans and experimental animals via both the corpus callosum and the reticular formation.¹²

In newborns with EIEE or EME, tonic seizures are a predominant feature. In EIEE the prevailing initial seizure type is tonic seizures, whereas in EME tonic seizures develop in the course of the disease. Interestingly, Djukic et al.⁹ pointed out that the two conditions represent a continuum of progressive pathology and dysfunction and that the presence versus absence of tonic seizures indicates the severity of the brainstem pathology or dysfunction at the time the syndrome presents. If the EEG shows a burst-suppression pattern, tonic seizures usually correlates with the burst (Fig. 1). In such cases prognosis remains poor. Clinically tonic seizures involve axial and limb muscles are of brief duration, and may present with abrupt onset resembling an epileptic spasm or epileptic myoclonus. However contractions persist and last longer than either spasms or myoclonus. Focal signs consisting of asymmetric contraction or unilateral head or eye deviation may be present, depending on the presence of an underlying structural lesion.