Tonic seizures have long been recognized as a seizure type that often occurs in the setting of symptomatic generalized epilepsy, more specifically, as part of the Lennox-Gastaut syndrome. Although this may be the most common clinical scenario where tonic seizures are seen, they occur in other epilepsy syndromes and can also be a manifestation of focal epilepsy with secondary generalization. The prominent bilateral involvement of muscle groups led to classifying tonic seizures as a “generalized” seizure type, and though true in many patients, a variety of electroencephalographic (EEG) patterns and clinical phenomena have been described. This chapter will address tonic seizures across the age spectrum, with particular attention paid to specific clinical and neurophysiologic correlates.

Historically, tonic seizures were recognized as a distinct seizure type by Gastaut and colleagues in 1963, when they described in detail the different types of tonic seizures based on clinical and electrophysiological observations.¹ This observational study described distinct subtypes of tonic seizures based on the involvement of specific muscle groups. A common feature of all types of tonic seizures is sustained tonic contraction of different muscle groups without evolution into a clonic phase. Clinically, five different types were described: tonic axial, tonic axorhizomelic, global tonic, asymmetrical and unilateral tonic, and tonic seizures terminating with a brief clonic phase.¹ Gastaut et al. also noted that these seizures often occurred during sleep and were brief, lasting between 10 and 50 seconds. Nearly 50 years after this initial description, the underlying pathophysiology of tonic seizures remains poorly understood, despite the fact that they are often refractory to medical management and associated with significant cognitive impairment.

The International League Against Epilepsy (ILAE) describes a tonic seizure as a rigid, violent muscular contraction, fixing the limbs in some strange position. There is usually deviation of the eyes and the head towards one side, and this may amount to rotation involving the whole body (sometimes actually causing the patient to turn around, even two or three times). The features are distorted; the colour of the face, unchanged at first, rapidly becomes pale and then flushed and often livid as the fixation of the chest by these spasms stops the movements of respiration. The eyes are open or closed; the conjuctiva is insensitive; the pupils dilate widely as cyanosis comes on. As the spasm continues it commonly changes in its relative intensity and different part causing slight alterations in position of the limbs.²

This description highlights the focal and autonomic features that may be present in tonic seizures. Bilateral, symmetric (or asymmetric) tonic seizures may be generalized or focal in onset, whereas unilateral tonic seizures are most likely focal in onset, originating from the contralateral hemispheric. Chatrian and colleagues used the term tonic-autonomic seizures to emphasize the autonomic alterations often present during tonic seizures.³ The most common alteration was arrest of respiration, followed by a gasp or loud snort and, less commonly, pupillary dilation or flushing of the face.

The classic interictal EEG signatures of a predisposition to generalized tonic seizures include generalized spike-wave (GSW) discharges (often 2.5 Hz or less) and generalized paroxysmal fast activity (GPFA), superimposed on a slow or disorganized background. However, multifocal or focal sharp waves may also be present in patients with generalized or focal tonic seizures.

The ictal EEG hallmark of most tonic seizures is low amplitude, fast activity, often intermixed with, or obscured by, muscle artifact. Gibbs and Gibbs noted that “recordings during these show either flattening of the electroencephalogram, or a grand mal type of discharge.”⁴ Gastaut and colleagues referred to this pattern as desynchronization, defined as “replacement of fundamental rhythms during the seizure by an activity which is more rapid and of lesser amplitude. Sometimes this activity is of such a low amplitude that it is scarcely visible, the recording appearing like a simple flattening out of the EEG.”¹ Other tonic seizures are accompanied by higher amplitude and relatively slower activity—hypersynchronization, according to Gastaut et al.—defined as “the appearance during the seizure of an activity of much greater amplitude and of relatively lower frequency, at times equal or even inferior to that of the basic rhythms. This hypersynchronous activity generally appears as a rhythm of 10 Hz and of amplitude rapidly increasing to a maximum of about 50–100 μV.”¹ Other terms used to describe the EEG during a tonic seizure are fast paroxysmal rhythms, generalized repetitive fast discharge,⁵ runs of rapid spikes,⁶ generalized rhythmic 15 to 20 Hz activity, spike and sharp waves (that resemble medication artifact), beta band seizure pattern,⁷ and GPFA.

Initially, the region of onset of a tonic seizure was believed to be the pontobulbar structures, leading to the term lowest level fits.⁸ This hypothesis is supported largely by electrostimulation of the brainstem in animals resulting in a similar clinical manifestation of tonic contraction of the neck and limbs,⁹ as well as similar generalized attenuation of EEG activity.¹⁰ Such a hypothesis invoked involvement of various brainstem pathways, including the ascending reticular activating system or diencephaloreticulospinal tract, resulting in secondary cortical involvement; the clinical behavior was believed to be a result of a release phenomenon.¹¹ However, intracranial EEG records in patients with symptomatic generalized epilepsy and tonic seizures do not support this localization (Video 14-1). The intracranial EEG findings in Video 14-1 illustrate the cortically based low-amplitude fast activity that is commonly seen with tonic seizures. In this case, one can see the abrupt onset and offset of the ictus with a subtle yet persistent lead-in over the right hemispheric strip electrodes. Given the filtering properties of the skull and scalp, it should not come as a surprise why scalp EEG recordings of tonic seizure may show a generalized attenuation or electrodecrement. Furthermore, simultaneous thalamic and cortical recordings have shown subcortical involvement to be a secondary phenomenon.¹²

A consistent feature of generalized tonic seizures is the augmentation of epileptiform discharges during non–rapid eye movement (NREM) sleep, which has been described by many authors.^1,3,5 GPFA bursts lasting 1 to 3 seconds are common during sleep without clinical signs, whereas more prolonged bursts of GPFA often result in an electroclinical tonic seizure (Video 14-2: GPFA short and long during sleep).

Despite the variety of interictal and ictal EEG patterns, the final common pathway is an ictal event with prominent bilateral (or sometimes unilateral) motor phenomena. These various clinical and electrophysiological patterns have variable expression depending on the age of the patient and the underlying etiology of the epilepsy. The remainder of this chapter will focus on tonic seizures from neonates to adults, emphasizing specific epilepsy syndromes when possible.

Tonic seizures presenting in the first few days of life are often indicative of severe neurologic abnormalities.¹³ Early infantile epileptic encephalopathy (EIEE), or Ohtahara syndrome, is an extremely rare but devastating encephalopathy that manifests in neonates within the first 2 to 3 months of life. EIEE is characterized by frequent tonic seizures, profound mental retardation, and quadriplegia in the 50% who survive the neonatal period.^13–16 The unmistakable EEG hallmark of EIEE is a suppression-burst (SB) background on EEG whether awake or asleep.¹⁴ SB consists of 2 to 6 seconds of high-voltage (150–350 μV) bursts of polyspikes alternating at a relatively regular rhythm with a lack of electrical activity called suppression. Although the pathophysiology of SB is not clear, it may indicate subcortical excessive neuronal discharge modified by subcorticocortical dysregulation or disconnection.¹⁴

Most cases of EIEE appear to be caused by congenital structural brain malformations or cerebral dysgenesis; such lesions are typically asymmetrical and can be associated with porencephaly, Aicardi syndrome, cerebral atrophy, hemimegalencephaly, dentate-olivary dysplasia, linear sebaceous nevus syndrome, and migrational defects.^15–17 Some cases were originally considered cryptogenic, but postmortem pathology findings indicate that some of these may actually have involved developmental structural abnormalities too subtle to be detected on magnetic resonance imaging (MRI).^18,19 Inborn errors of metabolism, namely nonketotic hyperglycinemia, have been the identified cause in a minority of cases,²⁰ but the only familial cases of EIEE have been in a family with Leigh encephalopathy.¹⁵ Acquired brain injuries, resulting from hypoxic ischemic encephalopathy, central nervous system (CNS) infections, and trauma, do not typically cause EIEE.

Metabolic disorders and familial cases are more often associated with early myoclonic encephalopathy (EME), an epileptic disorder similar to EIEE that also shows an SB EEG pattern, early onset, intractable seizures, and psychomotor retardation.¹⁶ Although there is some controversy as to whether the two disorders are actually two points on the same spectrum,¹⁷ it is important to distinguish EIEE from EME because of their different seizure types and somewhat different etiologies. Compared with EIEE, EME tends to have an earlier onset, a more progressive, severe, and intractable course, the enhanced or exclusive presence of SB in sleep, a higher mortality rate in the neonatal period, and a poorer prognosis,¹⁷ although the prognosis in EIEE is already poor. Metabolic disorders are more frequently seen in EME than in EIEE, which may partly explain the especially poor prognosis. The most striking difference between these two epileptic encephalopathies is seizure type; EME involves mostly erratic myoclonus and partial seizures, whereas tonic spasms predominate in EIEE.

Patients with EIEE may have a variety of abnormal paroxysmal movements, not all of which may be epileptic seizures. The clinical utility of video-EEG monitoring (VEM) has been repeatedly demonstrated in the classification and diagnosis of such neonatal seizures.^21–24 In neonates in particular, distinguishing epileptic seizures from nonepileptic seizures, such as generalized tonic posturing or motor automatisms, or reflex movements without correlation to EEG is exceedingly difficult, and even highly trained electroneurodiagnostic technicians will misdiagnose 50% of clinical seizures.²² Neonatal seizures can also be either subclinical or very brief and subtle, and there is a poor correlation between clinical and electrographic neonatal seizures.^24–27 Quantifying precise seizure burden is not critical in EIEE, but correlating EEG to video is the only way to accurately measure seizure burden in such syndromes.

Tonic spasms in EIEE are usually very frequent, occurring singly or in clusters during sleeping or waking, and are thus amenable to relatively short-term VEM.¹⁴ These epileptic spasms often correspond to the burst portion of the SB EEG pattern, showing an initial high-voltage slow wave and then generalized fast activity.²⁸ However, the SB pattern can often disappear during a cluster of spasms.²⁹ The spasms are brief generalized tonic seizures that last up to 10 seconds and can involve asymmetrical flexion or extension of the extremities, asymmetric contraction of the trunk muscles causing the body to bend to one side, and conjugate deviation of the eyes to one side. Clusters consist of 10 to 40 spasms with 5- to 15-second intervals, and daily seizure burden is very high at 10 to 300 single spasms or 10 to 20 clusters. In addition to the tonic spasms, there may be some partial signs, such as isolated eye deviation or facial clonic seizures, particularly before a spasm cluster; other seizure types present in one third to one half of cases are focal motor seizures, hemiconvulsions, and, rarely, myoclonic seizures.²⁹

As a child ages, EIEE may evolve into other age-dependent epileptic encephalopathies, including West syndrome and the later-developing Lennox-Gastaut syndrome. These syndromes share frequent generalized minor seizures, profoundly abnormal EEG, and poor seizure, developmental, and cognitive prognoses.²⁹ Evolution along an age-dependent spectrum and common genetic mutations in the ARX gene support the idea that EIEE and West syndrome are related by a common mechanism.^30–33 Although the relative incidence of EIEE to West syndrome may be 1:40 or less,²⁹ the EEG of 75% of EIEE cases evolves around 3 to 6 months of age to hypsarrhythmia, which is typically asymmetrical. At ∼1 year of age, some evolve to more diffuse slow spike-waves, whereas others evolve into an EEG with multifocal or unifocal spikes; the EEG rarely can evolve to a diffusely slow background.^14,18 There is one case report of a persistent SB pattern in a 5-year-old patient with EIEE.³⁴

Seizures in EIEE are generally intractable, but they may be more responsive to treatment as they progress to West or Lennox-Gastaut syndrome. Adrenocorticotropic hormone (ACTH) and corticosteroids, valproate, phenobarbital, and benzodiazepines have minimal effect. Surgical procedures such as hemispherectomy and resection of cortical dysplasia may help improve seizure control in some cases, but no treatments have been demonstrated to consistently improve the symptoms or course of EIEE.³⁵

Although tonic seizures are a prominent feature in EIEE, they also occur in neonates without an SB pattern, and they may be very subtle or difficult to differentiate from normal neonatal behavior. When tonic events occur in neonates without an SB EEG, an important distinction should be made between focal tonic posturing and generalized tonic posturing. On VEM, focal tonic posturing often correlates with ictal activity on scalp EEG, whereas episodes of generalized tonic stiffening tend not to have an associated ictal EEG signature.^24,36 Clinically, focal tonic seizures manifest as asymmetric tonic posturing of the limbs or trunk or sustained deviation of the eyes. Involvement of axial muscles may result in asymmetric truncal flexion, and the EEG may show low-voltage, very fast, rhythmic seizure discharges arising from the frontotemporal region ipsilateral to the flexion.²⁴ This is in contrast to generalized tonic posturing/seizures, where there is often hyperextension of the upper and lower extremities with variable involvement of the torso and neck, and often no associated scalp EEG correlate.

There have been two major explanations for the lack of observed scalp EEG activity with generalized tonic events. One explanation suggests that such events are epileptic seizures generated by epileptic activity in subcortical nuclei, but cortical electrical seizure activity is absent because there is no projection of the epileptiform discharge from the subcortex to the cortex or because profound cortical depression prevents the expression of cortical seizure activity.³⁷ The alternative explanation is that generalized tonic events are not epileptic in character, but rather are primitive brainstem and spinal motor responses that have been unmasked due to a lack of normal cortical tonic inhibition.³⁷ Both of these theories have some plausibility, and it is impossible to prove or disprove either one in humans with current electrodiagnostic technology. Generalized tonic posturing/seizures often occur in the setting of diffuse background abnormalities, such as a depressed-undifferentiated pattern, episodic generalized voltage attenuations, or SB,²⁴ and this could result in either poor ictal propagation or “release” due to the profound cortical depression often seen in these infants.