Myoclonus epilepsy with ragged-red fibers
Nov. 06, 2023
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Generalized onset tonic seizures are the predominant epileptic seizures in Lennox-Gastaut syndrome and also occur in neonates and infants with severe epilepsy, like Ohtahara syndrome. Clinically, they manifest with symmetrical sustained increase in muscle contraction, usually lasting a few seconds to 1 minute. Severity varies from inconspicuous to marked clinical manifestations with falls depending on the extent and groups of muscles involved and violence of the attack. Ictal autonomic alterations are prominent. Consciousness is usually lost or impaired (cloudiness). They predominantly occur in sleep. Patients with generalized onset tonic seizures also suffer from concurrent atypical absences, tonic-clonic, atonic, and other types of epileptic seizures according to the primary epileptic syndrome. Interictal and ictal EEG are usually abnormal, but their features depend on the age of the patient and the syndrome with which these occur. Management is usually difficult, and prognosis is that of the underlying disorder. In this article, the author details the clinical manifestations, pathophysiology, EEG, neuroimaging, and optimal management of patients with generalized onset tonic seizures and related epileptic syndromes.
• Generalized onset tonic seizures are epileptic seizures of mainly severe epilepsies of neonates, infants, and children with learning difficulties who also suffer from frequent seizures of other types.
• Lennox-Gastaut syndrome is the prototype disorder of generalized onset tonic seizures.
• Generalized onset tonic seizures manifest with abrupt onset and termination of sustained increase in muscle contraction, usually lasting a few seconds to 1 minute.
• Severity varies from inconspicuous to marked clinical manifestations with falls depending on the extent and group of muscles involved and violence of the attack. Ictal autonomic alterations are prominent. Consciousness is usually lost or impaired (cloudiness). The seizures predominantly occur in sleep.
• Interictal and ictal EEG are usually grossly abnormal.
• Prognosis (usually poor) and management (usually difficult) is that of the underlying disease or syndrome.
ILAE classification and nomenclature. The ILAE Commission of 1981 classified tonic seizures as generalized seizures and cited the description of Gowers for their clinical manifestations:
…a rigid, violent muscular contraction, fixing the limbs in some strained position. There is usually deviation of the eyes and of the head toward one side, and this may amount to rotation involving the whole body, (sometimes actually causing the patient to turn around, even 2 or 3 times). The features are distorted; the color of the face, unchanged at first, rapidly becomes pale and then flushed and ultimately livid as the fixation of the chest by the spasms stops the movements of respiration. The eyes are open or closed; the conjunctiva is insensitive; the pupils dilate widely as cyanosis comes on. As the spasm continues, it commonly changes in its relative intensity in different parts, causing slight alterations in the position of the limbs (41; 18).
According to this ILAE classification:
• Tonic axial seizures with extension of head, neck, and trunk may also occur.
• Ictal EEG consists of “low voltage, fast activity or a fast rhythm of 9 to 10 c/sec or more, decreasing in frequency and increasing in amplitude”
• The EEG interictal expression is of “more or less rhythmic discharges of sharp and slow waves, sometimes asymmetrical. Background is often abnormal for age” (18).
Tonic seizures are defined as follows in the ILAE glossary: “a sustained increase in muscle contraction lasting a few seconds to minutes” (12).
The ILAE core group on classification classifies tonic seizures as generalized and explains, “The mechanism of tonic seizures is probably not the same as that of the tonic phase of generalized tonic-clonic seizures. Generalized tonic seizures typically occur in Lennox-Gastaut syndrome and occasionally in epilepsy with myoclonic astatic seizures” (30). The more recent proposals of the ILAE Commission maintain that tonic seizures should be classified amongst generalized epileptic seizures (08; 17).
The ILAE Commission diagnostic manual of the epilepsies describes generalized tonic seizures as follows (17):
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.
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.
NOTE: Tonic seizures are one type of seizure that 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.
Caution: Consistent focality of spikes or maximal amplitude of ictal rhythm, then consider focal seizure.
Differential diagnosis: Epileptic spasms: the motor contraction is often shorter in duration (< 2 seconds), epileptic spasms often occur in a series; Focal seizure - supplementary sensorimotor cortex of frontal lobe; Syncope; Non epileptic seizures.
Related syndromes: Lennox-Gastaut syndrome; Epilepsy with myoclonic-atonic seizures (17)
The latest ILAE position paper of the operational classification of seizure types recognizes that tonic seizures can be of focal or generalized onset. The generalized tonic seizures are classified as motor generalized seizures together with tonic-clonic, clonic, myoclonic, myoclonic-tonic-clonic, myoclonic-atonic, atonic, and epileptic spasms (32; 33).
Historical aspects. Gowers described tonic seizures as cited above whereas tonic axial seizures were first described by Hughlings Jackson who called them "trunk fits" or "respiratory fits" (41; 45; 46) and considered them as "lowest level fits" proposing that a primary discharge of the pontobulbar centers induced discharges in the spinal motor centers and secondarily involved higher centers via ascending pathways. He distinguished tonic seizures from epileptic seizures arising in the cerebral hemisphere. However, these were also frequently referred to as "tetanoid attacks" or "tonic postural attacks" and confused with nonepileptic tonic attacks in subjects suffering from intracranial hypertension often related to a tumor in the posterior fossa, the "cerebellar fit" ("cerebellar attack," posterior fossa seizure or decerebrate seizure) (37). They often have also been grouped with other nonepileptic attacks, sometimes referred to as "extrapyramidal seizures" (which are usually localized, or at least asymmetrical, and are frequently related to known cerebral pathology), as well as with the syndrome of "paroxysmal choreoathetosis" (37).
Our current knowledge of tonic seizures is mainly based on the meticulous investigations by Henri Gastaut and his school in Marseilles who studied 30 cases in which tonic seizures were observed and recorded cinematographically, electroencephalographically, electromyographically, electrocardiographically, and pneumographically (38; 37). They found and pointed out:
• Tonic seizures occur almost uniquely in children in association with or precedence of infantile myoclonic encephalopathy with hypsarhythmia (one quarter of cases) and diffuse subcortical pathology.
• Clinically, they manifest as (a) tonic axial seizures, (b) tonic axo-rhizomelic seizures, (c) global tonic seizures, (d) asymmetrical and unilateral tonic seizures, and (e) tonic seizures terminating with a brief clonic phase. Autonomic manifestations are common and consist of extreme tachycardia, irregular tachypnea mixed with apneic periods, systolic hypertension, a positive psychogalvanic reflex, mydriasis, vasomotor phenomena, increased intravesicular pressure, glandular hypersecretion, and occasional piloerection. There is loss of consciousness and occasional postictal confusion. Generally, reflexes are diminished during and increased after the seizure. Their duration is between several seconds to 1 minute (usually 10 to 20 sec). Nocturnal predominance regularly occurs.
• Status epilepticus is to be especially feared as with passing seizures the striking motor manifestations diminish whereas impairment of consciousness and autonomic phenomena (especially bronchial secretions) are enhanced.
• An association with other seizure types is common, especially the spasms of hypsarhythmia or tonic-clonic epilepsy.
• Ictal EEG always shows bilateral, symmetrical, and synchronous discharges. Rapid desynchronization with or without subsequent rapid synchronization, pure hypersynchronization at 10 Hz (the epileptic recruiting rhythm), termination by added slow wave activity appearing as spike-waves, or other patterns may be seen. In one patient similar seizures may be associated with different EEG elements, or similar tracings with different intensities of seizures.
• On EMG there is a tendency for brief seizures to start acutely and long seizures to start progressively.
• It is important to differentiate them from other tonic seizures of epileptic and nonepileptic origin, with particular emphasis on generalized tonic-clonic seizures, the infantile spasms with hypsarhythmia, partial adversive seizures, other epileptic seizures, convulsive syncopes, cerebellar fits, tetanus, rabies, strychnine poisoning, and hysteria.
• Possible pathophysiological mechanisms: a type of generalized seizures outside of the classical dichotomy of generalized tonic clonic and absence seizures.
• Intractability to treatments and the significance of urgent management of status epilepticus.
Tonic seizures have been mainly studied in Lennox-Gastaut syndrome (38; 16) and neonatal epileptic encephalopathies such as Ohtahara syndrome (24; 63).
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