Myoclonus epilepsy with ragged-red fibers
Jun. 10, 2021
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Typical absence seizures (previously known as petit mal) are brief (seconds in duration) generalized epileptic seizures of abrupt onset and abrupt termination. They have 2 essential components: (1) clinically, the impairment of consciousness (absence) and (2) EEG generalized 3 to 4 Hz (less than 2.5 Hz) spike-and-slow wave discharges. Typical absences are clusters of clinico-EEG manifestations that may be syndrome related. Absences may be the only type of seizures occurring in the patient, as in childhood absence epilepsy, or may be mild and nonpredominant, as in juvenile myoclonic epilepsy. Typical absences are fundamentally different and pharmacologically unique compared to any other type of seizures, which also makes their treatment different. Antiepileptic drugs effective for focal seizures may be deleterious for absence seizures. In this article, the author details developments in the pathophysiology, genetics, and pharmacological treatment of absence seizures and related epileptic syndromes.
• Typical absence seizures (previously known as petit mal) are brief (seconds in duration) generalized epileptic seizures of abrupt onset and abrupt termination.
• The defining manifestations of typical absence seizures are impairment of consciousness and generalized 3 to 4 Hz spike-wave discharges.
• Typical absences are fundamentally different and pharmacologically unique compared to any other type of seizures, which also makes their treatment different.
• The clinico-EEG manifestations of absence seizures are syndrome-related. Childhood and juvenile absence epilepsy are the archetypal syndromes of typical absences.
• Typical absences, particularly in adults, are frequently misdiagnosed as focal seizures with detrimental effect on patient management.
• Antiepileptic drugs effective for focal seizures may be deleterious for absence seizures.
Poupart, in 1705, was the first to describe absences (122). Tissot described a girl with absences “avec un tres leger movement dans les yeux” and frequent generalized tonic-clonic seizures (126). The term “epileptic absence” was first used by Calmeil (20). Shortly thereafter, Esquirol coined “petit mal” (42). Gowers gave a most accurate description of the absence seizures “without conspicuous convulsions” (60). Friedman reported a long-term favorable prognosis, but believed that these absences were not epileptic (50). Sauer coined the name “pyknolepsy” (from the Greek word pyknos, meaning closely packed, dense, or aggregated) (115). Adie defined pyknolepsy as follows (02):
…a disease with an explosive onset between the ages of 4 and 12 years, of frequent short, very slight, monotonous minor epileptiform seizures of uniform severity, which recur almost daily for weeks, months, or years, are uninfluenced by anti-epileptic remedies, do not impede normal and psychical development, and ultimately cease spontaneously never to return. At most, the eyeballs may roll upwards, the lids may flicker, and the arms may be raised by a feeble tonic spasm. Clonic movements, however slight, obvious vasomotor disturbances, palpitations, and lassitude or confusion after the attacks are equivocal symptoms strongly suggestive of oncoming grave epilepsy, and for the present they should be considered as foreign to the more favorable disease.
Gibbs and colleagues described the clinico-EEG characteristics of absences (53). The petit mal triad of Lennox (77), which was misused and misunderstood, was clarified by the Commission of the International League Against Epilepsy with the differentiation of typical from atypical absences (52). Both Penry and colleagues and Stefan and colleagues studied absences with video-EEG (105; 119). Panayiotopoulos and colleagues described syndrome-related characterization of typical absence seizures with video-EEG analysis (103; 101; 102; 99).
A more detailed history of typical absence seizures can be found in a review publication (18).
Terminology and clarifications. Typical absences are brief, generalized epileptic seizures of sudden onset and termination. They have 2 essential components: (1) clinically the impairment of consciousness (absence) and (2) EEG generalized 3 to 4 Hz (more than 2.5 Hz) spike-and-slow wave discharges (28; 99).
Typical absences are a cluster of clinico-EEG manifestations that may be syndrome related.
Impairment of consciousness may be severe, moderate, mild, or inconspicuous (the detection of which may require special cognitive testing). This is often associated with other symptoms, such as automatisms, autonomic disturbances, or regional (mouth or eyes) or widespread (head, limbs, and trunk) rhythmic or random myoclonia.
The EEG discharge may be brief or long (lasting 30 seconds or more); it may be continuous or fragmented; and it may be composed of single or multiple spikes, which may or may not be consistent with the slow wave.
The intradischarge frequency may be relatively constant or may vary. Typical absences may be either spontaneous or precipitated by hyperventilation or other specific modes of precipitation (eg, photic, pattern, video games, thinking.
They may remit with age or be lifelong, requiring continuous treatment.
Thus, the clinico-EEG manifestations of typical absences are, by definition, widespread and often not as classical as in their archetype, childhood absence epilepsy. The prefix “typical” is not to characterize them as “classical,” but to differentiate them from “atypical” absence seizures.
Atypical absences differ from typical absences in the following ways (96; 97; 98):
• Atypical absences occur only in the context of mainly severe symptomatic or cryptogenic epilepsies of children with learning difficulties, who also suffer from frequent seizures of other types such as atonic, tonic, and myoclonic seizures.
• In atypical absences, onset and termination is not as abrupt as in typical absences, and changes in tone are more pronounced.
• Ictal EEG of atypical absence is of slow, less than 2.5 Hz, spike-and-slow wave. The discharge is heterogeneous, often asymmetrical, and may include irregular spike wave and slow wave complexes and other paroxysmal activity. Background interictal EEG is usually abnormal.
• The final distinguishing characteristic involves the neural circuitry involved in the spike-wave discharge. In typical absence seizures, the epileptiform activity is constrained within thalamocortical circuitry. In contrast, there are experimental, clinical, behavioral, and neuroimaging data for the involvement of both thalamocortical and limbic circuitry in atypical absence seizures. Thus, the progression of ictal events and the mechanisms by which these recruit several brain areas may provide an explanation for the differing characteristics of typical versus atypical absence seizures (128). See atypical absence seizures.
The ILAE classification core group recognized typical, phantom, myoclonic, and atypical absences and defined them as follows (41):
Typical absences. The pyknoleptic manifestations of typical absences in childhood absence epilepsy have been suggested to differ by shorter duration from the longer duration, less-frequent absences of juvenile absence epilepsy. However, based on what we currently know, it seems likely that they do not represent 2 mechanisms, but merely the evolution of a single mechanism as the brain matures.
Phantom absences. Phantom absences also are likely to be a result of brain maturation. A working group will be convened to study whether absences of childhood and juvenile absence epilepsy represent 2 seizure types or a spectrum of the same seizure type, and to better define associated motor components.
Myoclonic absences. The myoclonic components of these seizures are rhythmic (2.5 to 4.5 Hz) clonic rather than myoclonic and have a tonic component. The seizure type should be called something else, but there is no agreement on another name at this time.
Atypical absences. There are variable manifestations of this ictal event, some involving hypotonia and atonia. Better criteria for characterizing atypical absences will also be discussed by the working group on atonic seizures.
Absence seizures can rarely represent propagation from localized cortical areas, usually in the frontal lobe. There may be a continuum between these events and generalized atypical absences (41).
According to the 2014 ILAE Commission, absence seizures should be simplified in (A) typical absences, (B) atypical absences, and (C) absence with special features (eg, myoclonic absence, eyelid myoclonia) (11; Commission on Classification and Terminology of the International League Against Epilepsy 2014). The latest ILAE position paper of the operational classification of seizure types recognizes typical absences, atypical absences, absences with eyelid myoclonia, and myoclonic absences (47; 48). In this paper, absences are classified as "generalized nonmotor (absence) seizures" though this (nonmotor) does not convey the complex semiology of absence seizures, which often manifest with significant motor manifestations as analyzed in a narrative review (127). The ILAE Commission diagnostic manual of epilepsies describes typical absence seizures as follows (Commission on Classification and Terminology of the International League Against Epilepsy 2014):
Typical absence seizure. A typical absence seizure is a generalized seizure with abrupt onset and offset of altered awareness, which can vary in severity (see specific syndromes). Memory for events during the seizures is usually impaired, although there may be some retained awareness particularly for adolescents. Clonic movements of eyelids, head, eyebrows, chin, perioral, or other facial parts may occur, most typically at 3 Hz. Myoclonus of limbs can rarely occur. Oral and manual automatisms are common, and there may be perseveration of behaviors occurring prior to seizure onset. Absence seizures were previously known as “petit mal” seizures. Absence status epilepticus can occur.
Caution. Individual absence seizure longer than 45 seconds or with a post-ictal phase, then consider focal seizure.
Caution. Onset of absence seizures less than 4 years, then consider glucose transporter disorders.
EEG. Background/Interictal/Activation: Please refer to specific syndromes and etiologies in which this seizure type occurs.
Ictal EEG. Generalized spike-and-wave is mandatory. Regular 3 Hz generalized spike-and-wave occurs with typical absence seizures in childhood absence epilepsy. In absence seizures beginning in adolescence, faster irregular 3.5 to 6 Hz generalized spike-and-wave and polyspike-and-wave occurs.
Caution. Slow spike-and-wave (less than 2.5 Hz), then consider atypical absence seizures.
• Absence with eyelid myoclonia: repetitive, rhythmic, fast (greater than 4 Hz) jerks of the eyelids, with upward deviation of the eyeballs, and with head extension; often very frequent and provoked by photic stimulation
• Myoclonic absence: 3 Hz myoclonic jerks of upper limbs with tonic abduction
• Atypical absence: more prolonged subtle altered awareness often seen in individuals with intellectual disability
• Focal seizures with dyscognitive features
• Childhood absence epilepsy
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