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PubMed1995

A sensitive and semi-quantitative pediatric myoclonus evaluation scale.

One of the difficulties in evaluating myoclonus in childhood is the lack of a standardized scale which addresses the constraints of pediatric scoring. The scale needs to be simple and rapid as well as sensitive and semi-quantitative and applicable across different ages. We videotaped children and young adults with myoclonus of various etiologies, such as progressive myoclonus epilepsy, opsoclonus-myoclonus and other acquired etiologies, and scored the videotapes using a new scale. Each clinical type of myoclonus (spontaneous, action and sensory-evoked myoclonus) was graded separately on a five-point scale for severity, intensity and distribution. Data were evaluated as separate scores and also combined for a total score. Validity and reliability were tested using a judge panel of three blinded, trained observers. Action myoclonus was the predominant form of myoclonus in our patients, and was significantly greater than spontaneous and sensory-evoked myoclonus in frequency, intensity and distribution. Separate statistical analysis performed for progressive myoclonus epilepsy and for opsoclonus-myoclonus showed the same pattern. Total scores between etiologies of myoclonus for frequency and distribution categories were significantly different. Subscores and total scores were highly correlated. We found the new scale to be flexible and adaptable for children and there were few missing values due to non-applicability of a scale item. It was useful for all pediatric age groups. The scale and videotape instructions provide a reliable tool for use in pediatric myoclonic disorders.

Adolescent↗

PubMed1997

Myoclonus due to chlorambucil in two adults with lymphoma.

OBJECTIVE: To report myoclonus due to chlorambucil therapy in two adults with lymphoma, and to review the literature of chlorambucil neurotoxicity in adults. CASE SUMMARIES: Case 1: An 81-year-old man with lymphoma being treated with chlorambucil developed jerking movements and stiffness that persisted for 3 days and intensified at night. The dosage of chlorambucil was decreased with a subsequent decrease in symptomatology. Resolution of the myoclonus occurred with discontinuation of the chlorambucil. Rechallenge evoked a return of tremors the next day that later became constant and again resolved on discontinuation of chlorambucil. Case 2: A 75-year-old woman with lymphoma being treated with chlorambucil developed jerking movements in her limbs, particularly in her arms and right hip. The symptoms were so severe they prevented the patient from leaving her house. All symptoms resolved within 2-3 days after the cycle was completed and did not return. She was diagnosed as having had chlorambucil-induced myoclonus. DATA SOURCES: Searches were performed on MEDLINE, CancerLit, and Science Citation Index Review to identify reports and articles discussing chlorambucil-induced neurotoxicity, particularly myoclonus. DISCUSSION: Chlorambucil-induced myoclonus has been described in overdose situations and in the treatment of nephrotic syndrome in children. Three cases of reversible myoclonic activity associated with high-dose chlorambucil in adults have also been described. In each case, the myoclonus resolved following discontinuation of the drug. Only one other conclusive case of low-dose chlorambucil-induced myoclonus in an adult has been described. The two cases presented here are unique in that the myoclonus occurred in adults receiving low-dose chlorambucil who had no myoclonus before or after treatment with the drug. CONCLUSIONS: From the cases reviewed, it appears that chlorambucil may induce myoclonus in adults receiving therapeutic dosages of chlorambucil. The neurologic status of patients receiving chlorambucil should be followed closely during treatment. If myoclonus develops, drug-induced myoclonus should be considered, as well as discontinuation of the drug.

Aged↗

PubMed2000

[A pharmacological profile of piracetam (Myocalm), a drug for myoclonus].

Myoclonus is defined as shock-like, brief involuntary abnormal movements in muscle jerking caused by external stimuli; and it arises from progressive myoclonus epilepsy, post-anoxic encephalopathy and Alzheimer's disease, causing disabling symptoms. It is a rare syndrome but very difficult to control. Piracetam (2-oxo-1-pyrrolidineacetamide, Myocalm) was developed more than 30 years ago as a cyclic derivative of gamma-aminobutyric acid (GABA); it has been used in European countries for the treatment of memory loss and other cognitive defects in patients. Some reports have suggested that piracetam has anti-myoclonus activities, but the mechanisms of myoclonus are not well-identified, and thus there have been few preclinical studies on piracetam for the treatment of myoclonus. We investigated the effect of piracetam and clonazepam, an anti-epileptic drug, on high dosage urea-induced myoclonus using an electromyogram in rats. The incidence of myoclonus induced by urea 4.5 g/kg (i.p.) was significantly reduced by piracetam at 300 mg/kg (i.p.) and by clonazepam at 0.3 mg/kg (p.o.). The coadministration of piracetam 100 mg/kg (i.p.) and clonazepam at 0.03-0.1 mg/kg (p.o.) significantly reduced the incidence of myoclonus, although separate administration was not effective. After oral administration of piracetam, it is rapidly and completely absorbed and excreted almost unchanged in the urine; however, it does show a little binding to human serum protein. Repeated oral administration of piracetam for 7 days in phase-I trials did not show any accumulation of the drug. In the placebo-controlled double-blind crossover trial of piracetam conducted in the UK, there was a significant improvement in cortical myoclonus. In phase-II trials, piracetam inhibited myoclonus and showed an improvement in the quality of life (QOL) of the patients. These results show that piracetam has a beneficial use in clinics for severe myoclonus patients when it is combined with anti-epileptic drugs, demonstrating an improvement in the myoclonus and QOL of patients.

Animals↗

PubMed1975

Electroencephalographic correlates of myoclonus.

In order to overcome various drawbacks of the conventional polygraphic study of a relationship between myoclonus and EEG, the EEG preceding and following the myoclonic jerk was simultaneously averaged by the CNV program. The subjects were 7 patients presenting with myoclonus of various kinds. The conventional polygraphs showed various paroxysmal EEG activities in 4 patients, but none of those paroxysmal activities was temporally related to myoclonus except for one case. As a result of the present averaging technique, 2 patients with cerebellar ataxia with intention myoclonus showed myoclonus-related EEG spikes or spike-and-slow-waves in the contralateral central or centroparietal region. These myoclonus-related spikes preceded the myoclonus by 10-17 msec, suggesting the presence of a discharging focus in the deep cerebral structures, rather than in the cerebral cortex, in these cases. Two other patients, one with resting myoclonus and the other with postural myoclonus, showed myoclonus-related slow waves on the contralateral hemisphere. This previously undescribed method of averaged polygraphic recording will be very useful in detecting an EEG correlate of spontaneously occurring myoclonus.

Adolescent↗

PubMed1985

Physiological sleep myoclonus in baboons.

Physiological sleep myoclonus (sleep onset myoclonus and myoclonus during paradoxical sleep) was recorded from the tails of 6 baboons (2 Papio hamadryas and 4 Papio papio) and its relationship with spontaneously occurring EEG paroxysmal discharges was studied. It was observed that during light slow wave sleep tail myoclonus (sleep onset myoclonus) was almost always associated with EEG paroxysmal discharges predominating in the fronto-rolandic cortex. During deep slow wave sleep the number of EEG paroxysmal discharges decreased and tail myoclonus disappeared. In contrast, during paradoxical sleep tail myoclonus became more frequent even in the absence of cortical paroxysmal discharges. Though at present we do not know whether sleep onset myoclonus is triggered or not by cortical paroxysmal discharges, we propose that sleep myoclonus (sleep onset myoclonus and myoclonus of paradoxical sleep) is independent of these discharges but that, at a given moment, the two phenomena may be coupled by a hypothetical subcortical pacemaker.

Animals↗

PubMed1985

Myoclonus in the rat induced by p,p'-DDT and the role of altered monoamine function.

Administration of p,p'-DDT to rats produced myoclonus, but unlike previous studies in mice, this was not decreased by administration of clonazepam. Precursors of 5-hydroxytryptamine (5-HT) (L-tryptophan and L-5-HTP) reduced the intensity of myoclonus, but the 5-HT agonists, quipazine and Org 6582 did not. Antagonists of 5-HT (methergoline, methysergide and cinanserin) did not potentiate the myoclonus induced by p,p'-DDT. Drugs altering the function of dopamine and noradrenaline (apomorphine, clonidine or phenoxybenzamine) also had no effect on this myoclonus. Administration of monoamine oxidase inhibitors (MAOIs; pargyline, nialamide and tranylcypromine) markedly attenuated the myoclonus, an effect that could not be attributed to an action on any one monoamine system. No observable changes in cerebral biochemical parameters of 5-HT occurred at the onset of myoclonus, although tryptophan and 5-hydroxyindoleacetic acid (5-HIAA) in brain were increased following periods of prolonged myoclonus. Electrophysiological analysis of the myoclonus in the rat induced by p,p'-DDT revealed changes in EEG and EMG activity which suggested an origin for the myoclonus in the brainstem. Although this was similar to electrophysiological findings in some human patients with post-anoxic action myoclonus, the pharmacological studies suggest that the myoclonus induced by p,p'-DDT in the rat is not a suitable model for screening potential drugs to be used in the treatment of this disorder.

Animals↗

PubMed2000

Myoclonus associated with the use of gabapentin.

PURPOSE: To report on the occurrence of myoclonus in patients receiving gabapentin (GBP) for the treatment of epilepsy. METHODS: Clinic charts of 104 consecutive patients started on GBP were reviewed. All patients were treated by the same physician, and most were specifically asked about the presence of myoclonus. RESULTS: We found 13 cases of myoclonus. All patients had refractory epilepsy and were taking other antiepileptic drugs (AEDs). Six patients had a severe chronic static encephalopathy; five patients had no medical diagnosis other than seizures. Ten patients developed multifocal myoclonus. Three patients developed focal myoclonus, contralateral to their epileptic focus. Two patients had an exacerbation of preexistent myoclonus. An EEG performed during myoclonus on three patients showed no correlate. The myoclonus tended to persist as long as GBP was maintained, whereas discontinuance of GBP resulted in rapid cessation of the myoclonus. In all cases the myoclonus was subtle and did not significantly interfere with daily activities. CONCLUSIONS: GBP-associated myoclonus appears to be relatively frequent. It is usually mild and can easily be overlooked. Discontinuation of therapy is not necessary in most cases.

Acetates↗

PubMed1999

The incidence and prevalence of myoclonus in Olmsted County, Minnesota.

OBJECTIVE: 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. DESIGN: Descriptive study with case ascertainment through a records-linkage system. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Adolescent↗

PubMed1986

Action myoclonus, Ramsay Hunt syndrome, and other cerebellar myoclonic syndromes.

Action myoclonus, reviewed in this chapter, is the term applied to arrhythmic muscular jerking induced by voluntary movement. It is made worse by attempts at precise or coordinated movement (intention myoclonus) and may also be provoked by certain sensory stimuli. The effective stimuli for action myoclonus is probably feedback from muscle afferents, although it may be initiated by corollary discharge from motor cortex to reticular formation before or at the onset of voluntary movement. The condition is usually associated with diffuse neuronal disease such as post-hypoxic encephalopathy, uremia, and the various forms of PME, although action myoclonus may be limited to one limb in some cases of focal cerebral damage. It is caused by hyperexcitability of the sensorimotor cortex (cortical reflex myoclonus) or reticular formation (reticular reflex myoclonus), or both. No consistent pathological change has been reported in autopsied cases of action myoclonus. The underlying disorder appears to be a loss of inhibitory mechanisms involving serotonin and possibly GABA as transmitter agents. The term PME is used for the association of myoclonus with degenerative changes in the nervous system which are commonly diffuse but may predominate in certain systems. There may or may not be associated tonic-clonic seizures, other manifestations of epilepsy, or dementia. Those cases of PME associated with Lafora inclusion bodies and cerebral storage diseases can be distinguished from the system degenerations. Systems which may be involved in the latter group include cerebellodentatorubral, pyramidal, extrapyramidal, optic, auditory, posterior columns and gracile and cuneate nuclei, spinocerebellar pathways, motor neurons of cranial nerves and anterior horns, and muscle fibers. Confronted with this diversity of pathological change, it seems unnecessary to make any clinical distinction between Ramsay Hunt syndrome and Unverricht-Lundborg syndrome (Baltic myoclonus) because cerebellar signs are found in patients described under both headings. Additional systems may be involved in individuals or families who are otherwise typical. All three names could well be joined in an eponymous title (Unverricht-Lundborg-Hunt disease) or the condition simply known as the systems degeneration type of PME, as Halliday (43) suggested. The cause of the condition (or spectrum of conditions) is at present unknown. Action myoclonus usually responds to sodium valproate or clonazepam, and some individuals, particularly those with posthypoxic myoclonus, improve with the administration of serotonin precursors.

Adolescent↗

PubMedDate not supplied

Animal models of myoclonus.

This is a comprehensive review of animal models of myoclonus with particular emphasis on posthypoxic myoclonus and other newer chemically induced models. A stimulus-sensitive myoclonus was developed by experimentally inducing cardiac arrest in rats. The etiology, pharmacology, and neurochemistry associated with this model are consistent with posthypoxic myoclonus in humans. The complex etiology of posthypoxic myoclonus and the effectiveness of diverse pharmacological therapies in this movement disorder suggest that multiple interactive neurological mechanisms are operative. The p,p'-DDT-induced animal model of myoclonus differs from posthypoxic myoclonus in terms of its neurochemical and pathophysiological mechanisms. Also, micro-injection of compounds that modulate specific neurotransmitter systems in select brain regions induces myoclonus in normal animals, suggesting that these chemically induced models may be useful in understanding the intricate neurochemical and neuroanatomical mechanisms associated with myoclonus. The experimental evidence demonstrates that these novel animal models of myoclonus have salient neurological characteristics, reasonable predictability of novel antimyoclonic agents, and pathophysiological similarities to the disorder in humans. Thus, these animal models of myoclonus have the potential to provide us with valuable information about the disorder that is not readily obtainable by other means.

Animals↗

PubMed2000

Involvement of GABA(A) receptors in myoclonus.

Alterations in multiple neurochemical systems have been reported in animal and human studies of posthypoxic myoclonus. It is impossible, however, to establish causative relationships between the observed changes and the myoclonic movements from these studies. Therefore, to establish causative links between neurochemical changes and myoclonus, ligands that target neurotransmitter systems that are altered in posthypoxic myoclonus were microinjected into the lateral ventricles of normal rats to identify the changes that can produce myoclonus. Of the ligands that were tested, only the GABA(A) antagonists produced myoclonus after intracerebroventricular administration, suggesting the importance of disinhibition of GABAergic systems in myoclonus. To further examine the role of GABA in myoclonus, GABAergic antagonists were microinjected into the nucleus reticularis of the thalamus (NRT), an area of the brain in which extensive pathologic changes are seen in posthypoxic animals. GABA(A), but not GABA(B), antagonists produced myoclonus after microinjection into the NRT. Earlier investigators have further reported the ability of GABA(A) antagonists to produce myoclonus after microinjection into the caudate. The data therefore suggest that disruption of activity at GABA(A) receptors at any one of a number of levels in the neural axis can produce myoclonus.

Animals↗

PubMed2001

[Myoclonus in the adult: diagnostic approach].

Myoclonus, defined as shock-like involuntary movement, may be physiological or caused by a very wide variety of hereditary and acquired conditions. Because myoclonus can originate from different disorders and lesions affecting quite varied levels of the central and peripheral nervous systems, it represents from many points of view a diagnostic challenge. Moreover, new entities have been recently individualized, such as cortical tremor, which deserve renewed attention. The aim of this review is to propose a rationale for a diagnostic approach based on clinical and electrophysiological grounds. In this setting, we successively address 1) the clinical features allowing a positive diagnosis of myoclonus; 2) the clinical clues to the etiology; 3) the relevance of the clinical context to the diagnosis; and 4) the contribution of neurophysiology. Differentiating myoclonus from tics, spasm, chorea and dystonia can be difficult, and a careful reappraisal of clinical features allowing precise identification is presented. Moreover, the topographical distribution of myoclonus, the temporal pattern of muscle recruitment, the condition of occurrence and the rhythm of the event, may provide clinical clues relevant to the diagnosis. Myoclonus without associated epilepsy, myoclonus with epilepsy, myoclonus with encephalopathy, parkinsonism and/or dementia represent overlapping clinical categories, although they remain useful for the diagnostic approach. Using electrophysiology (including back-averaging EEG, MEG, SEP, C-reflex studies) to determine the origin of myoclonus may not allow us to focus on the underlying condition. Indeed, in many instances, the myoclonus is cortical in origin, but the pathology is found elsewhere.

Alzheimer Disease↗

PubMed1977

Clinical, biochemical, and physiological features distinguishing myoclonus responsive to 5-hydroxytryptophan, tryptophan with a monoamine oxidase inhibitor, and clonazepam.

Fifteen patients with a variety of myoclonic syndromes were studied clinically, pharmacologically, and physiologically. CSF tryptophan, 5HIAA, and HVA were also measured. Of these patients, 8 were improved to varying degrees by therapy with 5HTP, tryptophan in combination with MAOI (but not tryptophan alone), and clonazepam. This group included 6 cases of post-anoxic myoclonus, one case of post-traumatic myoclonus and one undiagnosed case of non-progressive focal myoclonus and epilepsy. In this group low levels of CSF 5HIAA were found compared to non-responsive cases and controls. Two cases of dysynergia cerebellaris myoclonica, 2 cases of undiagnosed aetiology, 2 cases of essential myoclonus, and one case of palatal myoclonus failed to respond to drug therapy. However, even amongst the responsive group the improvement varied. The most dramatic responses were seen in those patients in whom physiological study suggested that myoclonus was mediated by brain-stem structures. Less dramatic responses were seen in patients in whom the myoclonus appeared to originate from cortical structures. The neurochemical basis of myoclonus responding to 5HT precursors and clonazepam is discussed. It is suggested that such myoclonus arises from a relative hypoactivity of the 5HT neuronal system which results in a release of abnormal responses to sensory stimuli which characterize this type of myoclonus.

5-Hydroxytryptophan↗

PubMed2002

The serotonin hypothesis of myoclonus from the perspective of neuronal rhythmicity.

A quantitative analysis of two rat syndromes of myoclonus are presented, modeling myoclonic epilepsy and postanoxic myoclonus. Like the human conditions, both of the models benefit therapeutically from drugs that act on the serotonin system. The rat model of myoclonic epilepsy is associated with a profound loss of serotonin throughout the brain (except in the striatum) and is generated by an oscillator that is synchronized around the midline. The rat model of posthypoxic myoclonus does not demonstrate a significant reduction in serotonin in any location of its brain and is generated by a non-oscillating circuit in the medulla. Although some forms of myoclonic epilepsy may benefit from serotonin drugs because they are caused by a decrease in brain serotonin, our data indicate that posthypoxic myoclonus is not caused by a decrease in the serotonergic innervation of any region of the brain. That the raphe nuclei do not degenerate after global brain ischemia was noted by C. David Marsden in a discussion of the histologic findings of three of his human cases of posthypoxic myoclonus (page 117 of reference 10) and led him to question the hypothesis that posthypoxic myoclonus was due to a loss of serotonin neurons. Our data confirm his observation in the rat, but also indicate that density of serotonin fibers and terminals throughout the brain is not reduced by the brain ischemia that produces posthypoxic myoclonus. It remains to be determined whether the physiologic responsiveness of serotonin neurons is altered by global brain ischemia and whether changes in serotonin release or serotonin receptor properties are associated with posthypoxic myoclonus. The stability of the serotonin system in posthypoxic myoclonic rats is remarkable when one considers the wide range of disorders that is produced by the prolonged brain ischemia. The inability of the most severely posthypoxic myoclonic rats to perform 7-Hz tongue protrusions indicates substantial physiologic disruption of brainstem motor function. Moreover, the posthypoxic myoclonic rat suffers from ataxia, seizures, retrograde amnesia, and impaired ability to learn. The wide spectrum of these deficits is sharply constrasted by its apparently intact serotonin system. We have identified the inferior olive as a locus that may generate the rhythmic components of tremor and myoclonus in syndromes that are truly associated with a dramatic loss of brainstem serotonin. Serotonin acts within the inferior olive to constrain its rhythmic firing. Without intraolivary serotonin, olivary neurons are predisposed to oscillate continuously, providing a substrate upon which sustained rhythmic spiking may be superimposed. It is clear that such unconstrained rhythmicity produces synchronized whole-body tremor at 10 Hz (33, 41-43). The effects of serotonin to suppress olivocerebellar rhythmicity are mediated by postsynaptic 5-HT2 receptors that reduce the magnitude of the low-threshold calcium conductance, IT. It is notable that dysregulation of this conductance has been associated with hyper-rhythmic states in the thalamus underlying cognitive disorders ranging from depression to tinnitus (49), indicating a common mechanism underlying a variety of neurologic conditions. The identification of a specific brainstem locus (inferior olive), serotonin receptor 5-HT2, and ionic current IT involved in a form of rhythmic myoclonus may provide multiple clues toward which future pharmacotherapies can be directed.

Amnesia, Retrograde↗

PubMed2002

Why do Purkinje cells die so easily after global brain ischemia? Aldolase C, EAAT4, and the cerebellar contribution to posthypoxic myoclonus.

The experiments strongly suggested that the reason why Purkinje cells die so easily after global brain ischemia relates to deficiencies in aldolase C and EAAT4 that allow them to survive pathologically intense synaptic input from the inferior olive after the restoration of blood flow. This conclusion is based on: (a) the remarkably tight correspondence between the regional absence of aldolase C and EAAT4 in Purkinje cells and the patterned loss of Purkinje cells after a bout of global brain ischemia; (b) the necessity of the olivocerebellar pathway for the ischemic death of Purkinje cells; and (c) the build-up of pathologically synchronous and high-frequency burst activity within the inferior olive during recovery from ischemia. Indeed, the correspondence between the absence of aldolase C and EAAT4 to sensitivity to ischemia could be demonstrated for zones of Purkinje cells as small as two neurons. A second finding was that Purkinje cells are not uniformly sensitive to transient ischemia, since they die most frequently in zones where aldolase C and EAAT4 are absent. One implication of the experiment is that factors beyond the unique synaptic and membrane properties of Purkinje cells play an important role in determining this neuron's high sensitivity to ischemia. The data strongly imply that two properties of Purkinje cells that make them susceptible to ischemic death are their reduced capability to sequester glutamate and reduced ability to generate energy during anoxia. The patterned death of Purkinje cells is sufficient to induce a form of audiogenic myoclonus, as determined with a neurotoxic dose of ibogaine. Ibogaine-induced myoclonus is recognized behaviorally as a reduced ability to habituate to a startle stimulus and resembles the myoclonic jerk of rats during recovery from a prolonged bout of global brain ischemia. Commonalities of ischemia and ibogaine-induced neurodegeneration are the intricately striped Purkinje cell loss in the posterior lobe and a nearly complete deafferentation of the lateral aspect of the fastigial nucleus from the cerebellar cortex, in particular the dorsolateral protuberance. Thus, the data point strongly to a cerebellar contribution to audiogenic myoclonus. Single-neuron electrophysiology experiments in monkeys have demonstrated that the evoked activity in the deep cerebellar nuclei occurs too late to initiate the startle response (60) and electromyography of the postischemic myoclonus of rats corroborates this view (see Chapter 31) (20). However, the nearly complete loss of GABAergic terminals in the dorsolateral protuberance after Purkinje cell death would be expected to dramatically increase its tonic firing and the background excitation of the brain-stem structures that it innervates. The fastigial nucleus innervates a large number of autonomic and motor structures in the brainstem and diencephalon, including the ventrolateral nucleus of the thalamus and the gigantocellular reticular nucleus in the medulla--structures that have been implicated in human posthypoxic myoclonus (6, 7). We propose that the posthypoxic myoclonic jerk of rats is, at least in part, due to disinhibition of the fastigial nucleus produced by patterned Purkinje cell death in the vermis. The argument is as follows: the loss of GABAergic inhibition in the fastigial nucleus after ischemia leads to diaschisis of the motor thalamus and reticular formation which, in turn, is responsible for enhanced motor excitability and myoclonus. That the audiogenic myoclonus after global brain ischemia in the rat gradually resolves over a period of 2 to 3 weeks is consistent with this view, as restoration of background excitability after CNS damage in rats has been documented to occur within this time-frame (61). Our view brings together the physiologic finding that posthypoxic myoclonus appears to originate in the sensory-motor cortices and/or reticular formation with the consistent anatomical finding of Purkinje cell loss after ischemia, and explains the puzzle of Marsden's unique cases of myoclonus associated with coeliac disease (1). Moreover, our argument is consistent with findings both in rats (62, 63) and humans (64) that damage to the vermis impairs the long-term habituation of the startle reflex. It remains to be determined whether the pathologically enhanced startle responses after vermal damage resemble brain-stem reticular or cortical myoclonus at the electrophysiologic level of analysis. What is the purpose of the regional expression of aldolase C and EAAT4 in Purkinje cells? The close correspondence between the spatial distribution of aldolase C and the parasagittal anatomy of the cerebellum (48) has led to the view that aldolase C may help specify connectivity during development. While the present experiments do not address this issue, they underscore the fact that aldolase plays a fundamental role in metabolism. Because Purkinje cells have a repressed expression of aldolase A (31), whatever role the absence of aldolase C may play during development comes at the price of metabolic frailty later in adulthood. From another point of view, aldolase C and EAAT4 appear to confer upon Purkinje cells the ability to survive their own climbing fiber. Indeed, climbing fibers form a distributed synapse that synchronously releases glutamate (or aspartate) at all levels of the dendritic tree simultaneously (65, 66). Such synchronous activation triggers calcium influx throughout the Purkinje cell dendrites at a magnitude that is unparalleled in the nervous system (12), and, thus, places an extraordinarily high metabolic demand on the Purkinje cell. The apparently reduced level of aldolase in a subpopulation of Purkinje cells provides the condition for energy failure and death during anoxia so long as the climbing fibers are intact or when climbing fiber activation is pharmacologically enhanced under normoxic conditions, such as after ibogaine (53-56). Lastly, the argument that diaschisis produced by patterned cerebellar degeneration leads to thalamo-cortical and reticular hyperexcitability agrees with C. David Marsden and his colleagues' bold demonstration of an inhibitory influence of cerebellar cortex on motor cortex in humans (67). Our anatomic data indicate that the spatially distinct zones of Purkinje cells, which are killed by global brain ischemia, may be the origin of such inhibition.

Amino Acid Transport System X-AG↗

PubMed1993

[The classification of myoclonus].

The term "myoclonus" was originally used to indicate brief jerky involuntary movements. But, nowadays the meaning of myoclonus has expanded so much that its definition and classification have been considerably obscured. In this view, the definition of myoclonus is described and the characteristic clinical features are discussed. The classification of myoclonus is presented based on the pathophysiological observations. Myoclonus is divided into two large groups, cortical myoclonus directly associated with the activity of the motor cortex, and subcortical myoclonus which comprises various types of myoclonus (including spinal myoclonus). Furthermore, the electrophysiological aspects of myoclonus and its pathogenesis are briefly discussed.

Diagnosis, Differential↗

PubMedDate not supplied

Myoclonus in corticobasal degeneration.

Myoclonus occurs in about 50% of cases of corticobasal degeneration. The myoclonus is focal, affecting one arm or less commonly a leg. Action and reflex myoclonus, induced by sensory stimulation of the affected limb, are characteristic. Accordingly, the myoclonus of corticobasal degeneration has many of the clinical characteristics of cortical myoclonus. In contrast to the recognized forms of cortical reflex myoclonus, the myoclonus of corticobasal degeneration is not associated with enlargement of the secondary component of the cortical somatosensory evoked potential (SEP) or backaveraged electroencephalographic (EEG) spikes preceding each myoclonic jerk. Furthermore, the latency of reflex myoclonus in corticobasal degeneration is some 10 ms shorter than that seen in cortical reflex myoclonus. One explanation for these differences may be the preferential enhancement of different components of long-latency transcortical reflexes in different diseases. Changes in the sensory input to the cortex, alterations in the balance of local cortical excitatory and inhibitory influences, and therefore cortical excitability are likely to be important factors in determining the physiological characteristics of myoclonus of cortical origin.

Basal Ganglia↗

PubMed1997

[A case of cortical reflex positive-negative myoclonus--electrophysiological study].

An 11-year-old girl who had the positive-negative myoclonus and the history of the generalized tonic clonic seizure was electrophysiologically studied. She had no siblings with either myoclonus or epilepsy, and her intellectual level was normal. She had no other neurological deficits including ataxia, pyramidal and extrapyramidal signs. Surface EMG showed a brief increase in the EMG activity followed by the silent period associated with positive and negative myoclonus during sustained wrist extension. Giant SEP and C reflex (38.6 ms) following electric stimulation of the median nerve at the wrist were obtained in the resting condition and the silent period (about 180 ms) following C reflex was obtained during voluntary contraction. Jerk-locked back averaging of the EEG time-locked to the onset of the myoclonic discharge recorded from the right biceps muscle showed a cortical spike at the left central region preceding the myoclonus onset by 12.6 ms. The latency of C reflex in this case was very short compared with that of previously reported cortical reflex myoclonus. The estimated cortical delay between the arrival of the somatosensory volley and the motor cortex discharge responsible for the C reflex was -1.0 ms and this value was shorter than that in patients with typical cortical reflex myoclonus (mean 3.7 +/- 1.1 ms). Conditioning stimuli (C) of the right median nerve at the wrist started to facilitate the amplitude of the motor evoked potential recorded from the right abductor pollicis brevis muscle after magnetic test stimuli (T) of the left motor cortex at 20 ms of the C-T interval. This C-T interval was shorter than that (24.6 +/- 1.6 ms) in patients with the typical cortical myoclonus. These electrophysiological findings suggested the shorter reflex pathway of the cortical reflex myoclonus in this case than in typical cortical reflex myoclonus. We speculated that the myoclonus was based upon the direct sensory projection from the thalamus to the motor cortex in this case.

Child↗