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The Myoclonic Epilepsies

The term myoclonic had traditionally designated a large group of epilepsies characterized by repeated brief jerks, often responsible for multiple falls, severe seizures resistant to anti-epileptic drugs, and by an association with cognitive impairment . However, not all the ictal manifestations that cause falls are myoclonic, and not all myoclonic epilepsies predict poor outcome. myoclonic jerks are the only seizure type in but a minority of patients with myoclonic epilepsy which is commonly associated with generalized tonic-clonic seizures 2,3 as well as generalized clonic, atypical absence, and atonic seizures (4,5). Tonic seizures are uncommon myoclonic epilepsies, but isolated tonic attacks during sleep are not rare in children with myoclonic-astatic epilepsy (1,6). As a result, confusion arouse in classifying myoclonic epilepsies, because they represent a broad group of diseases and epilepsy syndromes that differ in evolution and prognosis.

a.) What is myoclonus?

Myoclonus, which is used to describe involuntary, jerky movements frequently involving antagonist muscles (7), can be classified physiologically as epileptic and nonepileptic. Epileptic myoclonus is an elementary electroclinical manifestation of epilepsy involving descending neurons, whose spatial (spread) or temporal (self-sustained repetition) amplification can trigger overt epileptic activity1. Myoclonus can have focal, mutlifocal, or generalized distribution 8. Epileptic myoclonus is characterized neurophysiologically by myoclonic elecromyographic(EMG) burst ranging between 10 to 100 milliseconds, synchronous EMG bursts or silent periods on antagonist muscles, and an EEG correlate by scalp electrodes or burst-locked EEG averaging (1).

Etiology- The vast majority of myoclonic epilepsies are idiopathic or cryptogenic, and genetic factors are important, as indicated by the frequency of epilepsy in family members. Mutations in the Beta1 and Alpha2 subunits of the sodium-channel receptor (SCN1B AND SCN2A) genes have been reported in a few patients with the MAE phenotype within generalized epilepsy with febrile seizures plus (GEFS+) families, as well as in patients with severe myoclonic epilepsy of infancy (Dravet syndrome) (9,10). A family with JME was found to harbor a mutations in the Alpha1 y-aminobutyric acid A GABA_a) receptor subunit (GABAA1) gene (11). These findings suggest that functional impairment of the ion channel may represent the pathophysiologic substrate for at least some of the nonprogressive myoclonic epilepsies. On the other hand, the progressive myoclonic epilepsies (PMEs) which are also genetically determined, follow an autosomal recessive inheritance and have been related to gene defects causing abnormal deposit material to accumulate in various organs including the brain.

Myoclonic Seizures chp 20 Clinical Features-319

A sudden, brief, involuntary, shock-like muscular contraction that results in a body movement is referred to as myoclonus(16,17) and my be epileptic or none epileptic. Myoclonic seizures are generalized seizures (13,14) that occur either as part of an idiopathic epilepsy syndrome or in encephalopathic generalized epilepsy.Myoclonic seizures are characterized by sudden, involuntary brief, muscle contracts of the head, trunk, or limbs. They usually occur without detectable loss of consciousness and may be generalized, regional or focal. They may be irregular or erratic, symmetrical or asymmetrical, synchronous or asynchronous, and positive or negative (18). Myoclonic seizures are often bilateral jerks that vary from subtle restricted twitches of the periocular or facial muscles to massive movements, with generalized involvement of arms and legs accompanied by falling or retropulsion (12). They occur singly or in repeated clusters, with some cognitive impairment note during prolonged clusters of myoclonic status epilepticus (12). The associated features, rather than the semiology of the myoclonic seizures themselves, define the syndromes associated with myoclonic seizures.

b.) Electrophysiology-The EEG

Myoclonic jerks associated with encephalopathic generalized epilepsy have high-amplitude, bisynchronous SSW or polyspike-and-wave discharge as the electrophysiologic correlate. A brief latency between shorts bursts and synchronized electromyographic potentials in agonist and antagonist muscles, and that of the corresponding spikes, occurs. The spike are time-locked events that are coupled with myoclonic jerks that follow. By using back-averaging techniques, latencies are found to occur between 21 and 80 milliseonds (19,20.) When a myoclonic jerk is generated by subcortical structures, a generalized spike discharge follows the first electromyographic sign of myoclonus;however, in this case an epileptogenic phenomenon is disputed by some (20). Negative myoclonus caused by a lapse of tone, which can be seen only during antigravity posture, is coupled with either the slow wave or the second positive component of a polyspike-and-wave discharge (20). Myoclonic seizures have correlates with an electromyographic pattern, demonstrating a brief synchronous potential of less thn 50 milliseconds that is seen simultaneously in the invloved muscle groups(41). During the jerks, medium-to high-amplitude repetitive 16hz spikes are seen.(21). The background activity of the interical EEG in patients with encephalopathic generalized epilepsy is characteristically diffusely slow. A unique EEG pattern is seen in early myoclonic encephalopathy and neonatal myoclonic seizures, with burst suppression or multiple paroxysmal abnormalities with random asynchronous attenuations (21).

c. Clinical Correlation- Most epilepsies with myoclonic seizures begin during the first of years of life (22). They are clinically and etiologically heterogeneous, and represent groups of disorders that may occur in many epilepsy types and syndromes from early infancy into adulthood (23,24). Myoclonic seizures must be differentiated from infantile spasms, partial seizures with tonic posturing and non-epileptic conditions 54, and difficulty may arrive in differentiating massive myoclonic seizures from tonic and atonic seizures. Causes of myoclonic seizures vary greatly from acquires causes of almost any etiology to familial epilepsies with varied inheritance patterns (23,24). The are subgroups of patients with idiopathic generalized epilepsy with refectory myoclonic seizures and developmental delay, yet with a genetic component. Myoclonic-astatic epilepsy and severe phenotypes of generalized epilepsy with febrile seizures pules (GEFS+) which mimic patients with encephalopathic generalized epilepsy, but with no discernible etiology and a genetic foundation for expression (26). Epilepsy with myoclonic astatic seizures is a syndrome intermediate between idiopathic and encephalopathic generalized epilepsy, with febrile seizures and subsequent myoclonic jerks during childhood that involve mainly the axial muscles, more than the face, upper trunk, and arms with jerks strong enough to cause patients to fall(astatic seizures) (27,28). Similarly, epilepsy with myoclonic absences is characterized by prolonged absence seizures with prominent rhythmic generalized myoclonic jerks involving both shoulders, arms, and legs, which may repeat at 3Hz during activation techniques, distinguishing myoclonic absence from childhood absence epilepsy. (36,58)

d.Pathophysiology-

It has been hypothesized that myoclonic seizures are produced by cortical and subcortical generator involving thalamocortical and reticular projections (19,20). Because of the wide variety of mechanisms associated with clinical expression of myoclonic seizures, no single pathology has been identified. In patients with encephalopathic generalized epilepsy, w wide range of pathologic substrates may exist, although frontal lobe abnormalities may preferentially occur (32). Genetic predisposition and/or the presence of a structural lesion underpin the best described pathphysiologic mechanism for myoclonic seizures with various modes of inheritance (23,33,34,) and the progressive myoclonic epilepsy syndromes have isolated gene loci involved in the majority of the disorders (61). Myoclonic seizures assoicated with chromosomal abnormalities (35), mutant mitochondrial DNA (36), ion channelopathies (9), and defects of neurotransmitter systems (11) form a wide variety of genetic influences that are reported.

e. Treatment-Valproate has broad broad-spectrum efficacy, with hpatient with myoclonic seizures responding in the majority of cases. Benzodiazepines, valproate, topirmate, zonisamide, and levetiracetam may all be effective AEDs in paitent with myoclonic seizures (38). Lamotrigine may either be effective (38) or aggravate (37) myoclonic seizures. The ketogenic diet should be considered if AEDs are innfective for mycolonic seizures (39)

References

Wyllie, Elaine (2006). The Treatment of Epilepsy. Lippincott, Williams and Wilkins. ISBN 0-7817-4995-6.