Epileptic Myoclonus Research Articles

Transcranial magnetic stimulation and epilepsy.

Epileptic conditions are characterized by an altered balance between excitatory and inhibitory influences at the cortical level. Transcranial magnetic stimulation (TMS) provides a noninvasive evaluation of separate excitatory and inhibitory functions of the cerebral cortex. In addition, repetitive TMS (rTMS) can modulate the excitability of cortical networks. We review the different ways that TMS has been used to investigate pathophysiological mechanisms and effects of antiepileptic drugs in patients with epilepsy and epileptic myoclonus. The safety of different TMS techniques is discussed too. Finally, we discuss the therapeutic prospects of rTMS in this field.

Similarities in Mechanisms and Treatments for Epileptic and Nonepileptic Myoclonus

Myoclonus is a disordered movement that may be an ictal phenomenon or may be due to various injuries in brain and spinal cord motor structures. Many epileptic and nonepileptic myoclonic conditions are associated with abnormalities in inhibitory neurotransmission. gamma-Aminobutyric acid type A (GABA(A))-receptor antagonists may trigger myoclonus. Several antiepilepsy drugs (AEDs) effective against myoclonic seizures [valproic acid (VPA), clonazepam (CZP), levetiracetam (LEV)] enhance GABAergic neurotransmission and improve myoclonic movement disorders. Together these associations suggest links between episodic disorders involving synchronous cortical discharges (seizures) and hyperkinetic movement disorders.

Similarities in Mechanisms and Treatments for Epileptic and Nonepileptic Myoclonus.

Myoclonus is a disordered movement that may be an ictal phenomenon or may be due to various injuries in brain and spinal cord motor structures. Many epileptic and nonepileptic myoclonic conditions are associated with abnormalities in inhibitory neurotransmission. gamma-Aminobutyric acid type A (GABA(A))-receptor antagonists may trigger myoclonus. Several antiepilepsy drugs (AEDs) effective against myoclonic seizures [valproic acid (VPA), clonazepam (CZP), levetiracetam (LEV)] enhance GABAergic neurotransmission and improve myoclonic movement disorders. Together these associations suggest links between episodic disorders involving synchronous cortical discharges (seizures) and hyperkinetic movement disorders.

A case of myclonus, resembling epileptic seizure, induced by short-term sulpiride treatment

An 86-year-old woman with delusional disorder was treated with oral sulpiride at a dose of 200 mg/day. On the seventh day of treatment, she suddenly developed abrupt brief rhythmical contractions every 5 s in her neck muscles, orofacial muscles, muscles of upper limbs and lower legs bilaterally. Although there was no impairment of consciousness, her speech was interrupted by the myoclonic episodes. We suspected that the epileptic seizure-like myoclonus might be a drug-induced acute extrapyramidal symptom. We therefore injected 5 mg of biperiden (i.m.), and the myoclonus ceased shortly thereafter. This myoclonus, resembling an epileptic seizure, did not recur subsequently after sulpiride treatment was discontinued. The present case shows that myoclonus can occur after even brief sulpiride treatment in certain elderly patients. (Int J Psych Clin Pract 2002; 6: 215-216 )

Transcranial Magnetic Stimulation in Disorders of Movement: The Therapeutic Outlook

Transcranial magnetic stimulation (TMS) has been proposed as a means of improving or restoring cortical function in psychiatric and neurologic disorders. Movement disorders have attracted the attention of neurologists interested in the use of TMS as treatment. In Parkinson's disease, physiologic data and some clinical trials suggest that TMS may have a beneficial effect on movement. However, some of the laboratory data have been impossible to replicate, and the trials have lacked appropriate controls. In focal dystonia and tic disorder, TMS may suppress abnormal movements, but the data are preliminary. In the epileptic movement disorder cortical myoclonus, benefits have been elusive so far. TMS may have therapeutic potential in movement disorders, but further work is needed.

Late-onset myoclonic epilepsy in Down’s syndrome (LOMEDS)

The aim of this paper is to report a patient with late-onset myoclonic epilepsy in Down’s syndrome (LOMEDS) as a differential diagnosis of adult-onset progressive myoclonic epilepsies. A 55-year-old male with Down’s syndrome (DS) is described who developed progressively frequent myoclonus and generalized myoclonic–tonic seizures (GMTSs) at the age of 52. EEG recordings demonstrated background slowing and generalized polyspike-wave discharges occasionally associated with myoclonic jerks, leading to the classification of primary generalized epileptic myoclonus. Descriptions of late-onset epilepsy in DS patients are rare. However, a review of the pertinent literature revealed at least two other cases of elderly DS patients developing progressive myoclonic epilepsy after the onset of dementia. We suggest that late-onset myoclonic epilepsy in Down’s syndrome as characterized here should be considered in the differential diagnosis of adult-onset myoclonic epilepsies. LOMEDS apparently shares features with myoclonic epilepsy in Alzheimer’s disease (AD) and Unverricht–Lundborg disease (ULD) caused by a mutation on chromosome 21. Since life expectation of DS patients has markedly increased, LOMEDS may be more frequent than currently acknowledged.

Postoperative myoclonus simulating seizure recurrence: a rare complication of anterior temporal lobectomy

The unusual case of newly-emerged bilateral myoclonus in a 39-year-old man following anterior temporal lobectomy, which cured his temporal lobe epilepsy, is reported. The possible causes and differential diagnosis between epileptic and non-epileptic myoclonus following epilepsy surgery are presented and a brief review of the available literature on the subject is reported.

The Incidence and Prevalence of Myoclonus in Olmsted County, Minnesota

To study the incidence and prevalence of diagnosed myoclonus in Olmsted County, Minnesota. Little is known about the frequency and distribution of myoclonus in the general population. Descriptive study with case ascertainment through a records-linkage system. We used a medical records-linkage system to identify all subjects whose records contained documentation of myoclonus or of diseases known to exhibit myoclonus. The records of all potential patients were reviewed by a neurologist, and only patients with pathologic and persistent myoclonus were included. Population denominators were derived from census data. The average annual incidence rate of pathologic and persistent myoclonus for 1976 through 1990 was 1.3 cases per 100,000 person-years. The rate increased with advancing age and was consistently higher in men. Symptomatic myoclonus was the most common type, followed by epileptic and essential myoclonus; dementing diseases were the most common cause of symptomatic myoclonus. The lifetime prevalence of myoclonus, as of January 1, 1990, was 8.6 cases per 100,000 population, and the prevalence increased with advancing age. Although our figures are probably under-estimated, they are the first attempt, to our knowledge, to measure myoclonus morbidity in the general population. We found clinical features and age and sex distributions different from those previously described in clinical series.

Mioclonías y Epilepsias Mioclónicas en la infancia

Myoclonic jerks occur in a number of different syndromes. There is many classifications of myoclonus. It is preferred the Fejerman classification, slightly modified that present the following five groups: 1. Myoclonus without encephalopathy and without epilepsy, which includes physiological myoclonus; 2. Encephalopathies with non epileptic myoclonus, which includes Kinsbourne syndrome and certain types of hyperekplexia which pose differential diagnosis problems with reflex myoclonic epilepsy; 3. Progressive encephalopathies with myoclonic seizures which includes typical and atypical progressive myoclonus epilepsies; 4. Epilepsies and epileptic encephalopathies with myoclonic seizures, which includes severe epilepsies which leads to mental retardation, as Otahara syndrome, West syndrome and Lennox-Gastaut syndrome, and other epilepsies which present sometimes myoclonic seizures, as Landau-Kleffner syndrome, 5. Comprises true myoclonic epilepsies, differentiating syndromes recognized as idiopathic, -benign myoclonic epilepsy of infancy, reflex form of benign myoclonic epilepsy in infancy, eyelid myoclonic with absences, perioral myoclonic with absences and juvenile myoclonic epilepsy-, cryptogenic-severe myoclonic epilepsy of infancy, myoclonic-astatic epilepsy and epilepsy with myoclonic absences-, and symptomatic as the generalized myoclonus in children with static encephalopathies. The epileptic syndromes of the last group are described. Despite this classification, apparently clear, there is still a great deal of confusion and in clinical practice, many cases are difficult to classify.

Myoclonus and epilepsy in childhood: 1996 Royaumont meeting.

Sudden and brief involuntary movements of central nervous system (CNS) origin called myoclonus may be cortical (motor strip), thalamocortical (thalamocortical loop) or reticular (caudal reticular formation). Epileptic, cortical and thalamocortical myoclonus are combined with a spike which, when it is focal, needs back-averaging to be demonstrated. Negative myoclonus due to lapse of tone can only be demonstrated during antigravidic posture and may be combined with either a slow wave or the second, positive component of a polyspike-wave. Epileptic myoclonus must be distinguished from epileptic spasms and tonic seizures, and from non-epileptic myoclonus, tics, tremor and chorea. Myoclonus may occur in partial symptomatic (mainly Rasmussen and dysplasia), cryptogenic (frontal) or idiopathic (negative myoclonus in CSWS) epilepsy. Generalized myoclonus is part of inborn errors of metabolism, non-progressive encephalopathy (mainly Angelman) and idiopathic epilepsy (juvenile and infantile benign and severe forms, and myoclonic-astatic epilepsy). Carbamazepine, vigabatrin and eventually lamotrigine may worsen myoclonus whereas it may be improved by benzodiazepines, valproate, lamotrigine, zonisamide and piracetam according to etiology. Pathophysiology must take in account maturation processes, lesions and genetic predisposition. However, precise mechanisms remain unknown and only hypotheses can be proposed, that could clarify the age-related EEG and clinical expression of the various syndromes.

Development of myoclonus in patients with partial epilepsy during treatment with vigabatrin: an electroencephalographic study

In the context of a study of the effects of γ-vinyl-GABA (GVG) on seizure occurrence and on EEG abnormalities we present three cases with focal epilepsy in which new clinical and EEG paroxysmal manifestations were observed during GVG therapy. At that time, whereas an amelioration or no change in patients' habitual seizures were observed, myoclonic jerks appeared with related changes in the EEG paroxysmal abnormalities, represented by generalized polyspike and wave complexes. An electroclinical correlation was recorded in one case. These data indicate that, although occurring rarely, it is possible to have epileptic myoclonus during GVG treatment. Mechanisms underlying these manifestations are difficult to explain. Probably a shift in the anti/proconvulsant GABAergic balance towards the latter may compromise the therapeutic effect of GVG.

Hereditary spastic paraplegia with epileptic myoclonus

A previously undescribed form of complicated hereditary spastic paraplegia with epileptic myoclonus in four affected offspring of consanguineous parents is reported. The disorder was inherited as an autosomal recessive trait. Age at onset varied from the prenatal period to 10 years. The main findings when examined between 26 and 42 years of age were spastic paraplegia, epileptic myoclonus, distal muscle atrophy, mental retardation or dullness, ataxia, hearing loss and a progressive course. The difference in phenotypic expression was striking. One woman had progressive epileptic myoclonus, ataxia and only slight distal wasting and could have been misdiagnosed as a case of Unverricht-Lundborg's disease. Thorough biochemical investigations revealed no cause of the disorder.

Drugs influencing the GABAergic neurotransmission have no effect on the non-epileptic myoclonus of baboons

In Papio papio baboons benzodiazepines can facilitate the appearance of a naturally occurring non-epileptic myoclonus, suggesting a possible role of GABAergic transmission in their physiopathology. Nevertheless, as this myoclonus is blocked by physostigmine, the effect of benzodiazepines is probably due to their indirect action on the cholinergic system. Therefore, in this study, we report the effects on the non-epileptic myoclonus of drugs influencing GABAergic transmission. Systemic injections of progabide (GABA precursor), baclofen (GABA B receptor agonist) and allylglycine (glutamic acid decarboxylase inhibitor) did not modify or induce the non-epileptic myoclonus. In the same way, localized chronic injections of GABA into various cerebral structures (prefrontal and motor cortical areas, reticular magnocellular nucleus and substantia nigra) had no effect. When the two types of myoclonus were present in the same photosensitive animal, the epileptic myoclonus induced by photic stimulation was blocked by benzodiazepines but was not influenced by physostigmine, thus differing from the non-epileptic myoclonus. This suggests that different neurochemical mechanisms are involved in the two types of myoclonus, the non-epileptic myoclonus not being directly influenced by the GABAergic transmission.

The Natural History of Dementia in Down's Syndrome

In a prospective longitudinal study with death as the end point in 17 middle-aged patients with Down's syndrome, dementia was clinically diagnosed in 15 patients, by means of careful observations in daily circumstances. Autopsies were performed in 10 cases: 8 demented patients and 2 nondemented patients. Neuropathologically, Alzheimer-type abnormalities were demonstrated in 9 patients, both demented and nondemented, and combined Alzheimer-type abnormalities with infarctions were demonstrated in 1 patient. In the 14 demented patients who did not show evidence of cerebrovascular or systemic vascular disease, dementia had an early onset and was rapidly progressive (mean age at onset, 51.3 years in the moderately retarded patients and 52.6 years in the severely retarded patients; mean duration of symptoms, respectively, 4.9 and 5.2 years). Cognitive and behavioral decline corresponded to symptoms of dementia of the Alzheimer's type in patients without Down's syndrome, but often were not recognized early. In the present group of patients, there was a remarkably high incidence of gait and speech deterioration. Also, the incidence of epileptic seizures and myoclonus was about eightfold, as compared with dementia of the Alzheimer's type in patients without Down's syndrome.

Unexpected potentializing effect of a tacrine derivative (9-amino-7-methoxy-1,2,3,4 tetrahydroacridine) upon the non-epileptic myoclonus in baboons Papio Papio

Švejdová Milada, Ivan Raktor, Carmen Silva-Barrat and Christian Menini: Unexpected Potentializinq Effect of a Tacrine Derivative (9-anino- 7 methoxy-1,2,3,4, tetrahydroacridina) upon the Non-Epileptic Myoclonua in Baboons Papio Papio. Prog. Nauro-Psychopharmacol. Biol. Psychiat. 1990, 14 : 961–966. 1. 1. The influence of 7-methoxytacrina (7-MEOTA) on the non epileptic myoclonus of the Papio papio baboon was studied in 5 animals. 2. 2. This type of myoclonus is thought to depend on a cholinergic system dysfunction since it can be induced by atropine and blocked by physostigmine. 3. 3. 7-MEOTA. a tacrine derivative, is believed to display a conspicuous anticholinesteraee activity but. surprisingly, it here potentiated the non epileptic myoclonus occuring either spontaneously or induced by atropine. 4. 4. In baboons not spontaneously presenting the non epileptic myoclonus. 7-MEOTA induced the myoclonus in a fashion similar to atropine) such a myoclonus was blocked by physostigmine. 5. 5. These data indicate a possible antagonist action of tacrine on the muscarinic acetylcholine receptor. From these data, it is suggested that caution is necessary when introducing a tacrine derivative in clinical practice.

Myoclonus: relation to epilepsy.

Myoclonus can be divided into those types which are fragments of epilepsy and those which are nonepileptic. Epileptic myoclonus is viewed as the effect of an isolated spike in neurons of the motor system. Cortical reflex myoclonus is a fragment of partial epilepsy and represents hyperactivity of a focal area of cerebral cortex. Reticular reflex myoclonus is a fragment of generalized epilepsy with hyperactivity of medullary brainstem reticular formation. Primary generalized epileptic myoclonus is a fragment of primary generalized epilepsy and may represent a generalized hyperactive response of cortex to subcortical input.

Primary generalised epileptic myoclonus: a frequent manifestation of minipolymyoclonus of central origin.

A group of patients with myoclonus is described whose jerks are preceded by a bilaterally synchronous, frontocentrally predominant, negative cerebral potential in the EEG. This potential may be a slow wave with variable timing in relation to EMG bursts, and in this circumstance the muscle jerks are usually small amplitude and multifocal ("minipolymyoclonus"). The cerebral negativity can also be shorter in duration and time-locked to limb jerks, which are larger in amplitude and more widespread. We propose that the physiology of this distinct form of myoclonus is similar to that of primary generalised epilepsy.

The use of positron emission tomographic scanning in epilepsy

Positron emission tomography (PET) with fluorine-18-labeled fluorodeoxyglucose (18FDG) has demonstrated the epileptogenic lesion in partial epilepsy to be hypometabolic interictally . This finding is useful for localizing the area of resection when surgical therapy is contemplated. 18FDG scans during partial seizures show increased metabolism in areas of ictal onset and spread and in other regions of decreased metabolism that could reflect postictal effects. In the generalized epilepsies, petit mal absences and generalized convulsions induced by electroconvulsive shock therapy (ECT) are associated with global hypermetabolism, while global hypometabolism is seen in the postictal period following ECT. More information about the factors that influence the interictal hypometabolic zone in partial epilepsy should improve the diagnostic value of this finding for presurgical localization and perhaps also for the evaluation of other therapeutic regimens. New techniques for more dynamic PET studies with improved resolution, combined with computerized electroencephalographic analysis, should allow more accurate interpretation of ictal, as well as interictal, phenomena. Application of PET technology to other paroxysmal disorders may provide a basis for new diagnostic classifications that have therapeutic and prognostic value and may allow clearer differentiation among epileptic phenomena, myoclonus, and movement disorders. More clinical and animal research is needed, however, before we can delineate fundamental mechanisms of human epilepsy from PET data. To this end, it is now possible to use combined multidisciplinary parallel approaches in patients and animals to define specific aspects of epileptic disorders clinically, to intensively investigate them with experimental models in the animal laboratory, and to verify the relevance of these experimental results by returning to clinical studies.

The evolution of different types of myoclonus during sleep. A polygraphic study.

(1) Epileptic myoclonus may persist, though decreasing, for the entire duration of sleep (Jacksonian epilepsy, epilepsia partialis continuans) or disappear in the lightest phases of sleep (degenerativ