Tonic status epilepticus is a serious, sometimes fatal disorder, which is seen mostly in children with neurocognitive impairment and severe epilepsy, such as Lennox-Gastaut syndrome. Tonic status epilepticus usually comprises repetitive tonic seizures, which might last for days to weeks or rarely even months. Characteristically, as the status progresses, motor symptoms tend to lessen whereas autonomic disturbances, including respiratory depression, become more prominent. Only electrographic evidence of tonic seizures might remain in the later stages. Video-EEG monitoring is usually needed for the recognition of autonomic status epilepticus, particularly when motor manifestations are minimal. There were a few earlier reports of tonic status epilepticus associated with benzodiazepines and valproate intake. Newer antiepileptic drugs, such as lacosamide, have been reported as effective. Although there are some reports on the efficacy of ketogenic diet in super refractory status epilepticus (SRSE) and febrile infection-related epilepsy syndrome (FIRES), the data specifically on tonic status epilepticus are lacking. Unfortunately, most of the systematic studies of tonic status epilepticus are dated 40 years ago, and more recent literature is very minimal. Available information on clinical manifestations, investigative procedures, pathophysiology, and optimal management of patients with tonic status epilepticus is reviewed in this article. Multicentric prospective registries are needed to provide further insight into the current status of this rare syndrome.
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• Tonic status epilepticus manifests with repetitive series of frequent tonic seizures that may last for weeks or months.
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• As the status progresses, autonomic manifestations, including respiratory depression, predominate and may lead to death.
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• Video-EEG monitoring may be necessary in later stages to identify ictal electrographic activity associated with very minimal clinical features.
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• Tonic status epilepticus occurs mostly in children with neurocognitive impairment and mainly in those with Lennox-Gastaut syndrome.
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• There are some rare case reports of acute symptomatic tonic status epilepticus in adults and the elderly.
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• Tonic status epilepticus may occur occasionally in association with the intake of benzodiazepines and valproate.
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• Newer antiepileptic drugs, such as lacosamide, appear promising in this condition.
Historical note and terminology
Tonic status epilepticus has been nearly exclusively studied systematically by Henri Gastaut and his Marseille School of epileptology (26; 24; 54; 45). Their classical work still remains the main source of information on the topic:
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Tonic status epilepticus. This variety is more frequent in children. The tonic spasms are repeated at a rate of four to twenty per hour and may progressively attenuate until no motor expression persists except recurrent superior conjugate deviation of the eyes. At this point, the attacks are usually recognized only if the EEG is monitored, but the autonomic phenomena continue and may even undergo progressive increase to terminate, during a period of relatively intact consciousness, in death from respiratory or cardiovascular failure (24).
The ILAE proposal of 1989 described status epilepticus in Lennox-Gastaut syndrome as “a frequent event, which might manifest as stuporous states with myoclonias, tonic, and atonic seizures” (11). The ILAE Task Force on classification classified tonic status epilepticus with other generalized types of status epilepticus (15) and gave the following description “Tonic status epilepticus most commonly occurs in patients with symptomatic generalized epilepsy but may occur in patients with idiopathic generalized epilepsy. In some of these patients, there appears to be an overlap of symptoms of idiopathic and symptomatic generalized epilepsy. Characteristically, when the patient is lying down, the neck is flexed, and the arms are flexed at the elbow and slightly elevated. The tonic spasms are brief and can continue at brief intervals for hours. In symptomatic generalized epilepsy, the duration of the status epilepticus can be much longer” (16).
The most recent ILAE proposal and the ILAE position papers on seizures and classification have not dealt specifically with status epilepticus (05; 19; 47). However, the report of the ILAE Task Force on the Classification of Status Epilepticus takes into consideration current knowledge regarding its pathophysiology and the need to address clinical treatment decision-making time points, as well as the conduct of epidemiologic and clinical studies (56). Accordingly, “status epilepticus is a condition resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms, which lead to abnormally prolonged seizures (after time point t1). It is a condition that can have long-term consequences (after time point t2), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures” (56). This definition is conceptual, with two operational dimensions: the first is the length of the seizure and the time point (t1) at which the seizure should be regarded as an “abnormally prolonged seizure.” The second time point (t2) is the time of ongoing seizure activity beyond which there is a risk for long-term consequences. In the case of convulsive (tonic-clonic) status epilepticus, both time points are based on animal experiments and clinical research. This evidence is incomplete, so these time points should be considered as the best estimates currently available. Data are not yet available for other forms of status epilepticus, but as knowledge and understanding increases, time points can be defined for specific forms of status epilepticus based on scientific evidence and may be incorporated into the definition, without changing the underlying concepts. This division into two time points has clear clinical implications: time point 1 determines the time at which treatment should be considered or started, whereas time point 2 determines how aggressively treatment should be implemented to prevent long-term consequences. The time domain may vary considerably between different forms of status epilepticus. This report provides no specific description or time points (t1 or t2) of tonic status epilepticus, which is simply classified among other types of status epilepticus with prominent motor features, which might occur in Ohtahara, West, and Lennox-Gastaut syndromes (56).
In the American Academy of Neurology practice parameter, tonic status epilepticus is cited amongst “convulsive status epilepticus that occurs with overt clinical signs, such as tonic, tonic-clonic, or clonic motor movements. Nonconvulsive status epilepticus occurs when either electrographic status epilepticus is associated with altered awareness without overt clinical signs, or altered awareness with subtle motor signs, such as minimal eyelid blinking” (44).
In the report of the 12, generalized onset tonic seizures are described as follows:
A generalized tonic seizure involves bilaterally increased tone of the limbs typically lasting seconds to a minute. They often occur out of sleep and in runs of varying intensity of tonic stiffening. The individual is unaware during these events. At the beginning of tonic seizures with more intense stiffening, individuals may make an expiratory sound. More severe and prolonged tonic seizures may have a vibratory component, which may be confused with clonic jerking. Tonic seizures often occur in individuals with intellectual impairment.
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Caution. Although asymmetry can occur in a generalized tonic seizure, if consistent focal features are seen from seizure to seizure, then consider focal seizure involving the frontal lobe.
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Note. Tonic seizures can result in a “drop attack” (also known as astatic seizure); other causes of drop attacks include myoclonic (especially in younger children), atonic, and myoclonic-atonic seizures.
EEG background/interictal/activation. Please refer to specific syndromes and etiologies in which this seizure type occurs.
EEG ictal. Tonic seizures show diffuse or generalized accelerating low amplitude paroxysmal fast activity, which is often bilateral and predominates in the anterior and vertex regions.
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When there is a consistent focality of spikes or maximal amplitude of ictal rhythm, a focal onset should be considered.
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• Epileptic spasms: The motor contraction is often shorter in duration (less than 2 seconds); epileptic spasms often occur in a cluster.
• Focal seizure: Supplementary sensorimotor cortex of frontal lobe
• Nonepileptic seizures
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• Lennox-Gastaut syndrome
• Epilepsy with myoclonic-atonic seizures
Adapted from (12).