Myoclonus epilepsy with ragged-red fibers
Jun. 10, 2021
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Myoclonic absences are typical absence seizures of sudden onset and offset that are associated with consistent, repetitive, and rhythmic myoclonic jerks during the ictus. The defining manifestations of typical absence seizures are impairment of consciousness and generalized 3 to 4 Hz spike-wave discharges. Clonic (rhythmic) and myoclonic (rhythmic, arrhythmic, singular) motor symptoms often feature at some stage of the absence, but these are rarely consistent, marked, and continuous. Myoclonic absences are mainly associated with the syndrome of “epilepsy with myoclonic absences” and “perioral myoclonia with absences.” Myoclonic absences are often misdiagnosed as focal motor seizures with adverse consequences on management. Effective antiepileptic medications are valproate, levetiracetam, ethosuximide, lamotrigine, and clonazepam, usually in combination. In this updated article, the author details developments in the clinical and EEG manifestations, etiology, prognosis, differential diagnosis, and pharmacological treatment of myoclonic absences and related epileptic syndromes.
• Myoclonic absences are typical absence seizures with repetitive myoclonic jerks during the ictus.
• The classical type of myoclonic absences manifests with rhythmic jerks of shoulders, arms, and legs with a concomitant tonic contraction during 3 to 4 Hz generalized spike-wave discharges. The jerks correlate with the spike and the tonic phase with the slow wave of the spike-slow wave discharge. This is the defining symptom of epilepsy with myoclonic absences.
• Another type of myoclonic absence seizures manifests with rhythmic jerks of perioral and/or eyebrow muscles during 3 to 4 Hz generalized spike-wave discharges; this is the defining symptom of facial myoclonia with absences.
• Myoclonic absences start in childhood and usually continue into adult life, often combined with generalized tonic-clonic and other types of seizure such as atonic.
• Etiology of epilepsy with myoclonic absences is varied whereas perioral and/or eyebrow (facial) myoclonia with absences is probably a genetically determined idiopathic generalized epilepsy.
• Myoclonic absences are often misdiagnosed as focal motor seizures though video-EEG recordings offer an unequivocal documentation of the correct diagnosis.
• Myoclonic absences are usually resistant to monotherapy with an appropriate anti-absence drug.
The first report of absence seizures with severe clonic or myoclonic jerks appeared in 1966 (35), but it was Tassinari and his associates who described and documented myoclonic absences as a specific seizure-type and included a few years later in the syndrome of epilepsy with myoclonic absences (70; 08; 07).
Panayiotopoulos and associates described and documented perioral myoclonia with absences as a seizure type that may also constitute an epileptic syndrome (58; 57).
ILAE classification and nomenclature. Myoclonic absences are a type of typical absence seizures with significant and continuous rhythmic (2.5 to 4.5 Hz) clonic rather than myoclonic symptoms and have a tonic component.
Typical absence seizures 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 (14; 56). Impairment of consciousness may be the only clinical symptom (simple typical absence seizures), but this is often combined with other manifestations (complex typical absence seizures).
In appreciation of this diversity, the ILAE Task Force on classification recognized 4 types of typical absence seizures, probably of different pathophysiology and syndromic significance: (1) the classical absence seizures of childhood and juvenile absence epilepsy, (2) myoclonic absences, (3) phantom absences, and (4) eyelid myoclonia with absence (26).
Myoclonic absences (the seizures) may feature either in normal or neurologically and mentally abnormal children. Epilepsy with myoclonic absences (the syndrome) was previously categorized among the “cryptogenic or symptomatic generalized epilepsies and syndromes” (15). The ILAE diagnostic scheme considers only the idiopathic form, which probably represents less than a third of the whole spectrum of epileptic disorders manifesting with myoclonic absences (25). The others are symptomatic or probably symptomatic cases. This syndrome is also recognized in the ILAE proposal and listed amongst the electroclinical syndromes with onset in childhood (04).
Perioral myoclonia with absences has not been recognized either as a seizure type or as a syndrome by the ILAE. That absences with perioral myoclonia is a discrete seizure type has been unequivocally documented with video-EEG recordings (58; 40; 03; 22; 76; 68).
The symptom of perioral myoclonia may also occur in absence seizures of idiopathic generalized epilepsy, and, as such, perioral myoclonia alone cannot be taken as sole evidence of the syndrome of perioral myoclonia with absences. However, there is often a nonfortuitous electroclinical clustering of symptoms indicating that these absences may often constitute the main symptom of a syndrome within the broad spectrum of idiopathic generalized epilepsy, which we proposed to call either perioral or facial (perioral and/or eyebrow) myoclonia with absences (58; 19; 55). Other manifestations of this syndrome include: generalized tonic-clonic seizures (GTCS), which often start early prior to or together with the absences; frequent occurrence of absence status epilepticus; resistance to treatment; and persistence in adult life.
In children the term facial myoclonia with absences is also used for the reason that some cases may present with perioral (45.5%) or eyebrow (41%) myoclonia with absences or even a combination of perioral and eyebrow myoclonia with absences (13.5%). The age of onset varies from 1 to 13 years (mean 5±3). EEG is generalized spike-wave or polyspike-wave discharges 2 to 4.5 Hz, duration 0.25 to 20 seconds. The response to valproate is 77%, increased to 91% if combined with ethosuximide. Typical absence seizures with facial or other myoclonias have variable clinical and EEG expression and those with GTCS have less favorable outcome (19). In the literature the syndrome is described with the title perioral myoclonia with absences that partially reflects the phenotype. Absence status epilepticus is very uncommon in children.
Cases with absence and myoclonic seizures, the predominant type of seizures in their phenotype, characterize the syndrome epilepsy with myoclonic absences and 2 syndromes in development, eyelid myoclonia and absences and facial (perioral and or eyebrow) myoclonia with absences (17).
In the ILAE “Epilepsy Diagnosis” manual, myoclonic absence seizures are considered as 1 of the 4 types of generalized absence seizures (typical, atypical, myoclonic, with eyelid myoclonia) and are described as follows (Commission on Classification and Terminology of the International League Against Epilepsy 2014):
Myoclonic absences. Myoclonic absences are rhythmic myoclonic jerks of the shoulders and arms with tonic abduction, which results in progressive lifting of the arms during the seizure. The myoclonic jerks are typically bilateral but may be unilateral or asymmetric. Perioral myoclonias and rhythmic jerks of the head and legs may occur. Seizures last 10 to 60 seconds and typically occur daily. Level of awareness varies from complete loss of awareness to retained awareness.
EEG Background. Please refer to specific syndrome in which this seizure type occurs.
Ictal EEG. Around 3 Hz generalized spike-and-wave. EMG recordings from the upper arm show a constant relationship between the bilateral myoclonic jerks and spike-and-waves.
• Typical absence (with marked clonic-myoclonic components)
• Epilepsy with myoclonic absences
According to the newest position paper of the ILAE Commission for Classification and Terminology:
A myoclonic absence seizure refers to an absence seizure with rhythmic three-per-second myoclonic movements, causing ratcheting abduction of the upper limbs leading to progressive arm elevation, and associated with three-per-second generalized spike-wave discharges. Duration is typically 10 to 60 s. Impairment of consciousness may not be obvious. Myoclonic absence seizures occur in a variety of genetic conditions and also without known associations (30; 29).
However, this ILAE operational classification of epileptic seizures has been criticized from a number of experts (Unterberg et al 2018; 48). A comprehensive assessment of absence seizures concludes that:
The classification as “generalized nonfocal and nonmotor (absence) seizure” does not covey the complex semiology of a patient's clinical events (73).
According to the various ILAE classifications and definitions, generalized onset clonic seizures are mainly distinguished from generalized myoclonic seizures by their rhythmicity only and nothing else. This has created significant overlap in what to call clonic or myoclonic seizures, and often these terms are used interchangeably. An example of this is “myoclonic absence seizures” in which the motor component is clonic rhythmic at 2.5 to 4.5 Hz, rather than myoclonic arrhythmic.
Generalized clonic seizures, by definition, manifest with bilateral rhythmic clonic convulsions only. Their duration varies from minutes to hours, but each clonic event lasts less than 100 ms at a rate of 1 to 3 Hz. Conversely, myoclonic seizures are defined as singular or irregular recurrent events as opposed to the clonic seizures that are rhythmic at 1 to 5 Hz. Clonic seizures also differ from other types of seizure that manifest with tonic components mixed with myoclonus (eg, eyelid myoclonia) (26).
The new ILAE position paper states that “clonic refers to sustained rhythmic jerking and myoclonic to regular unsustained jerking” and that “the distinction between clonic and myoclonic is somewhat arbitrary, but clonic implies sustained, regularly spaced stereotypical jerks, whereas, myoclonus is less regular and in briefer runs. Myoclonus differs from clonus by being briefer and not regularly repetitive. Myoclonus as a symptom has possible epileptic and nonepileptic etiologies” (29). In the glossary of the same paper, myoclonic is defined as “sudden, brief (< 100 msec) involuntary single or multiple contraction(s) of muscles(s) or muscle groups of variable topography (axial, proximal limb, distal). Myoclonus is less regularly repetitive and less sustained than is clonus”, as opposed to clonic, which is “jerking, either symmetric or asymmetric, that is regularly repetitive and involves the same muscle groups” (29).
Myoclonic seizures in childhood are usually brief, sudden, involuntary muscle contractions that may involve the whole or part of the body (focal, segmental) and may be single or repetitive, rhythmic or arrhythmic, unilateral or bilateral (massive), symmetrical or asymmetrical. The upper part of the body, particularly the head, is usually involved and the jerks maybe subjective or objective, recorded as slight, moderate, or marked jerks. The jerks occur at the onset, in the course of, or immediately after the generalized spike-wave discharges and absence seizure; usually brief (eyes open and stare) may precede or follow the jerk. During intermittent photic stimulation the provoked clinical phenomena are similar to the spontaneous or maybe the first manifestation.
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