Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027066 (myoclonus)
 4,275 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We made a comparative study of the anticonvulsant effect of GABA agonists on feline amygdala or hippocampal kindled seizures. Progabide (PGB) [gamma-aminobutyric acid (GABA) receptor agonist 25-100 mg/kg intraperitoneally, i.p.] significantly reduced both the kindled seizure stage and after discharge (AD) duration in a dose-dependent manner. SKF89976A (GABA uptake inhibitor 0.5-2.0 mg/kg i.p.) also significantly reduced the kindled seizure stage. Toxic doses of SKF89976A caused generalized paroxysmal EEG discharges and myoclonus, but AD generation in the kindled focus was suppressed completely. Furthermore, gamma-vinyl GABA (GABA catabolic enzyme inhibitor, GVG 50-200 mg/kg i.p.) significantly reduced the seizure stage, while causing prolongation of the AD duration. In contrast, baclofen (selective GABAB receptor agonist, 1 or 5 mg/kg) did not show anticonvulsant effects on any parameters of kindled seizures. Therefore, these GABA agonists, which potentiate the inhibitory function of the GABAA systems, have potent anticonvulsant effects on partial onset and secondarily generalized limbic seizures.
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PMID:Comparative study of the anticonvulsant effect of gamma-aminobutyric acid agonists in the feline kindling model of epilepsy. 824 67

A patient with adult onset Huntington's disease (HD) and prominent action myoclonus is described. Neither epileptiform activity nor electroencephalography (EEG) correlates of the movements was found. Unlike the case with most (nonmyoclonic) HD patients, centro-parietal components of somatosensory evoked potentials (SEPs) were well defined and a clear V2 response was found. Treatment with valproic acid greatly reduced myoclonus suggesting that the gamma-aminobutyric acid (GABA) system might be involved in the pathophysiology of myoclonus in HD.
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PMID:Adult onset myoclonic Huntington's disease. 847 90

The molecular mechanisms of myoclonus are unknown. Drugs used in the symptomatic treatment of myoclonus were developed for other indications, such as epilepsy. Antimyoclonic drugs are not a single family of compounds but rather constitute a heterogeneous group of agents that act at various sites along the metabolic pathway of neurotransmitters or as receptor agonists or antagonists. For some drugs, the mechanism of antimyoclonic action is obscure despite many known actions. Myoclonus is affected by manipulation of more than one neurotransmitter system, and the neurotransmitters most linked to myoclonus are gamma-aminobutyric acid (GABA), glutamate, glycine, and serotonin. This is a review of the pharmacology of drugs acting on those neurotransmitters that are known or potential antimyoclonic drugs. A time of continuing advances in molecular biology and drug development is propitious for the pharmacotherapy of disorders that historically have been so refractory to conventional drug treatment.
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PMID:The pharmacology of antimyoclonic drugs. 889 98

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.
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PMID:[A pharmacological profile of piracetam (Myocalm), a drug for myoclonus]. 1108 17

It is estimated that Angelman syndrome (AS) accounts for up to 6% of all children presenting with severe mental retardation and epilepsy. The main clinical features of AS may not be apparent early in life. Clinical findings present in all patients include developmental delay, which becomes apparent by 6-12 months of age, severely impaired expressive language, ataxic gait, tremulousness of limbs, and a typical behavioral profile, including a happy demeanor, hypermotoric behavior, and low attention span. Seizures, abnormal electroencephalography, microcephaly, and scoliosis are observed in >80% of patients. Approximately 70% of patients show a deletion involving the maternally inherited chromosome 15q11-q13, encompassing a cluster of gamma-aminobutyric acid receptor subunit genes, 3% show chromosome 15 paternal uniparental disomy (UPD), 1% harbor a mutation in the imprinting center (a transcriptional regulatory element), and 6% harbor intragenic mutations of the ubiquitin-protein ligase E3A (UBE3A) gene. Twenty percent of patients have no detectable genetic abnormality. Rare cases of familial recurrence of AS show either imprinting center (IC) or UBE3A mutations. Approximately 75% of cases are detected through the methylation test, which allows the detection of AS due to deletions, UPD and IC mutations. Mutation analysis of the UBE3A gene should be performed when the methylation test is negative. Individuals with chromosome 15q11-q13 deletions have a more severe clinical picture and are more prone to develop severe epilepsy. Epilepsy has typical features, including absence and myoclonic seizures, and insidious episodes of nonconvulsive or subtle myoclonic status which are easily overlooked as children appear apathetic or in a state of neurologic regression. Tremulousness, present in all patients even when seizures are well controlled or absent, is related to distal cortical myoclonus. Valproic acid (sodium valproate), benzodiazepines, and ethosuximide, in various combinations, are quite effective in treating the typical seizure types. Piracetam may help in reducing distal myoclonus. Carbamazepine and vigabatrin may seriously aggravate absence and myoclonic seizures and should be avoided. Cognitive, language, and orthopedic problems must be addressed with vigorous rehabilitation programs, including early physical therapy, which may help to develop communicative skills and prevent severe scoliosis and subsequent immobility. Where these treatment strategies are applied, individuals with AS may reach an appreciable level of integration, self care, and have a normal life span.
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PMID:Angelman syndrome: etiology, clinical features, diagnosis, and management of symptoms. 1451 Jun 23

Nova proteins are neuron-specific antigens targeted in paraneoplastic opsoclonus myoclonus ataxia (POMA), an autoimmune neurologic disease characterized by abnormal motor inhibition. Nova proteins regulate neuronal pre-messenger RNA splicing by directly binding to RNA. To identify Nova RNA targets, we developed a method to purify protein-RNA complexes from mouse brain with the use of ultraviolet cross-linking and immunoprecipitation (CLIP).Thirty-four transcripts were identified multiple times by Nova CLIP.Three-quarters of these encode proteins that function at the neuronal synapse, and one-third are involved in neuronal inhibition.Splicing targets confirmed in Nova-/- mice include c-Jun N-terminal kinase 2, neogenin, and gephyrin; the latter encodes a protein that clusters inhibitory gamma-aminobutyric acid and glycine receptors, two previously identified Nova splicing targets.Thus, CLIP reveals that Nova coordinately regulates a biologically coherent set of RNAs encoding multiple components of the inhibitory synapse, an observation that may relate to the cause of abnormal motor inhibition in POMA.
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PMID:CLIP identifies Nova-regulated RNA networks in the brain. 1461 40

The case of a 35-year-old woman with diaphragmatic myoclonus of four year duration is presented. The myoclonus deteriorated with anxiety, menstruation and orthostatism. It was frequently accompanied by urinary retention or incontinence. Several pharmacologic agents were shown to be ineffective until the myoclonus was suppressed with a combination of gabapentin and tiagabine. In this article, the respiratory center is proposed as the original focus of the myoclonus, a deficit of gamma-aminobutyric acid (GABA) in brainstem structures as its neurochemical substrate, and GABAergic enhancement as an effective therapeutic measure. The clinical manifestations, etiology, ancillary studies and treatment of diaphragmatic myoclonus are reviewed. Experimental evidence on the anatomical localization, physiology and neurochemistry of the respiratory center is examined. The authors try to relate some of the patient's clinical findings to the experimental data found in the medical literature. The action mechanisms of gabapentin and tiagabine are examined and these drugs are proposed as effective means of enhancing GABAergic neurotransmission and treating diseases with increased inspiratory drive.
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PMID:[Clinical and neurochemical aspects of diaphragmatic myoclonus]. 1461 52

The clinical and electrophysiological features of a truncal myoclonus in a 55-year-old man are described. The electromyographic characteristics point toward propriospinal myoclonus. It is suggested that a myoclonic generator was released after use of ciprofloxacin, by antagonising the gamma-aminobutyric acid metabolism.
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PMID:Propriospinal myoclonus after treatment with ciprofloxacin. 1573 19

The succinic semialdehyde dehydrogenase (SSADH) null mouse represents a viable animal model for human SSADH deficiency and is characterized by markedly elevated levels of both gamma-hydroxybutyric acid (GHB) and gamma-aminobutyric acid (GABA) in brain, blood, and urine. GHB is known to induce absence-like seizures and absence seizures have been reported to occur in children with SSADH deficiency. We tested the hypothesis that the phenotype of the SSADH(-/-) mouse shows absence-like seizures because of the inordinately high levels of GHB in the brain of this mutant animal. Sequential electrocorticographic (ECoG) and prolonged video ECoG recordings from chronically implanted electrodes were done on SSADH(-/-), SSADH(+/-), and SSADH(+/+) mice from postnatal day (P) 10 to (P) 21. Spontaneous, recurrent absence-like seizures appeared in the SSADH(-/-) during the second week of life and evolved into generalized convulsive seizures late in the third week of life that were associated with an explosive onset of status epilepticus which was lethal. The seizures in SSADH null mice were consistent with typical absence seizures in rodent with 7 Hz spike-and-wave discharge (SWD) recorded from thalamocortical circuitry, the onset/offset of which was time-locked with ictal behavior characterized by facial myoclonus, vibrissal twitching and frozen immobility. The absence seizures became progressively more severe from P14 to 18 at which time they evolved into myoclonic and generalized convulsive seizures that progressed into a lethal status epilepticus. The absence seizures in SSADH(-/-) were abolished by ethosuximide (ETX) and the GABA(B)R antagonist CGP 35348. The seizure phenotype in the SSADH(-/-) recapitulates that observed in human SSADH deficiency. Hence, SSADH(-/-) may be used to investigate the molecular mechanisms that underpin the pathogenesis of absence and generalized tonic-clonic seizures associated with SSADH deficiency. As well, the SSADH(-/-) may represent a unique animal model of the transition from absence to myoclonic and generalized convulsive seizures that is observed in up to 80% of patients with juvenile absence epilepsy.
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PMID:Absence seizures in succinic semialdehyde dehydrogenase deficient mice: a model of juvenile absence epilepsy. 1558 27

X-linked lissencephaly with abnormal genitalia is the first human disorder in which deficient tangential migration in the brain has been demonstrated. Male patients with X-linked lissencephaly with abnormal genitalia show intractable seizures, especially clonic convulsions or myoclonus from the first day of life, but neither infantile spasms nor hypsarrhythmia on electroencephalograms so far. Brain magnetic resonance imaging shows anterior pachygyria and posterior agyria with a mildly thick cortex, agenesis of the corpus callosum, and dysplastic basal ganglia. ARX, a paired-class homeobox gene with four polyalanine sequences, is a responsible gene for X-linked lissencephaly with abnormal genitalia. The brain of Arx knockout mice shows aberrant tangential migration and differentiation of gamma-aminobutyric acid (GABA)ergic interneurons. In human X-linked lissencephaly with abnormal genitalia, a neuropathologic study has suggested a loss of interneurons. Meanwhile, polyalanine expansion of ARX causes symptomatic or nonsymptomatic West's syndrome and nonsyndromic mental retardation. The striking epileptogenicity of X-linked lissencephaly with abnormal genitalia and West's syndrome associated with ARX mutations i s considered to be caused by a disorder of interneurons involving a tangentialmigration disorder. We propose "interneuronopathy" as a term for this.
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PMID:X-linked lissencephaly with abnormal genitalia as a tangential migration disorder causing intractable epilepsy: proposal for a new term, "interneuronopathy". 1592 Dec 44


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