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Query: UMLS:C0027066 (myoclonus)
 4,275 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several lines of clinical evidence suggest that myoclonus is caused by a reduction of serotonin in the brain and hyperactivity of the inferior olive. We determined whether a change in serotonin content within the olivocerebellar system accompanied a predisposition to myoclonus and investigated the necessity of the inferior olive for a myoclonic seizure. The experiments employed the genetically epilepsy-prone rat that exhibits a profound myoclonic seizure in response to an auditory stimulus. We found that these animals demonstrated a significant reduction in the serotonergic innervation of the inferior olive without a significant change in the serotonergic innervation at any other level of the olivocerebellar circuit. The deficit in olivary serotonin was verified physiologically and pharmacologically by a reduced sensitivity of the genetically epilepsy-prone rat to the tremorogenic effect of harmaline, which is known to produce tremor through a mechanism that requires serotonergic innervation of the inferior olive. We quantified the timing of the myoclonic seizure of the genetically epilepsy-prone rat and found that its large amplitude 2-6 Hz clonus was always preceded by 9-10 Hz tremor that was synchronized among limbs. Ablation of the inferior olive by 3-acetylpyridine abolished the myoclonic seizure. The specificity of the deficit in olivary serotonin, the timing of the seizure, and the demonstration of the necessity of the inferior olive for myoclonus suggest that pathological inferior olivary activity contributes to the genesis of a myoclonic seizure.
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PMID:Removal of the inferior olive abolishes myoclonic seizures associated with a loss of olivary serotonin. 948 43

We confirmed that the effects of inhibitors of nitric oxide (NO) synthase, such as Nomega-nitro-L-arginine methyl ester and Nomega-nitro-L-arginine, differ depending on several experimental factors. Both compounds but not their less active enantiomers delayed picrotoxin-induced clonus in mice yet increased the incidence of clonus following low-dose picrotoxin. Nomega-nitro-L-arginine methyl ester significantly reduced the latencies of both myoclonus and clonus in older but not younger Sprague-Dawley rats receiving pentylenetetrazol s.c. By contrast, there was no significant change in the latencies for myoclonus and clonus in Wistar rats (older and younger). However, when pentylenetetrazol was administered i.p. rather than s.c., Nomega-nitro-L-arginine methyl ester dramatically increased latencies of convulsive indicators, including tonus, in both Sprague-Dawley and Wistar rats. Nomega-nitro-L-arginine methyl ester also delayed tonus but not myoclonus or clonus in mice, regardless of the systemic route of administration of pentylenetetrazol. Both Nomega-nitro-L-arginine methyl ester and NG-nitro-L-arginine increased the tonic CD50 of pentylenetetrazol in mice and Nomega-nitro-L-arginine methyl ester delayed 4-aminopyridine-induced tonus. However, Nomega-nitro-L-arginine methyl ester reduced the tonic CD50 of both picrotoxin and 4-aminopyridine in mice and failed to suppress tonus following maximal electroshock. Evidently, inhibitors of NO synthase are not universally effective antitonic drugs.
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PMID:Further studies on anti- and proconvulsant effects of inhibitors of nitric oxide synthase in rodents. 957 Apr 42

This is a proposal of the Movement Disorder Society for a clinical classification of tremors. The classification is based on the distinction between rest, postural, simple kinetic, and intention tremor (tremor during target-directed movements). Additional data from a medical history and the results of a neurologic examination can be combined into one of the following clinical syndromes defined in this statement: enhanced physiologic tremor, classical essential tremor (ET), primary orthostatic tremor, task- and position-specific tremors, dystonic tremor, tremor in Parkinson's disease (PD), cerebellar tremor, Holmes' tremor, palatal tremor, drug-induced and toxic tremor, tremor in peripheral neuropathies, or psychogenic tremor. Conditions such as asterixis, epilepsia partialis continua, clonus, and rhythmic myoclonus can be misinterpreted as tremor. The features distinguishing these conditions from tremor are described. Controversial issues are outlined in a comment section for each item and thus reflect the open questions that at present cannot be answered on a scientific basis. We hope that this statement provides a basis for better communication among clinicians working in the field and stimulates tremor research.
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PMID:Consensus statement of the Movement Disorder Society on Tremor. Ad Hoc Scientific Committee. 982 89

To explore the possible involvement of glucocorticoids in the previously observed anticonvulsive effect of swim stress, mice were, prior to administration of convulsants, subjected to treatments that diminish or enhance plasma corticosterone levels. Aminoglutethimide, the inhibitor of steroid synthesis, failed to modify convulsant doses of picrotoxin, but enhanced threshold doses of pentylenetetrazole producing myoclonus and death, both in unstressed and stressed animals. The same drug prevented the effect of stress on pentylenetetrazole-induced running bouncing clonus (RB clonus) and abolished the appearance of tonic hindlimb extension (THE). Doses of kainic acid producing convulsions and death were not affected by stress, but they were enhanced by aminoglutethimide. Corticosterone administration could not imitate the effect of swim stress. Finasteride, a 5 alpha-reductase inhibitor, did not interfere with the effect of stress on picrotoxin-induced convulsions. Swim stress failed to modify the binding of the convulsant t[3H]-butylbicycloorthobenzoate [3H]TBOB, to washed mouse forebrain membranes. The results confirmed an anticonvulsant effect of swim stress against convulsions produced by GABA-related convulsants, but they do not support the hypothesis suggesting the involvement of glucocorticoids or neurosteroids in this effect.
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PMID:Anticonvulsive effect of swim stress in mice. 1097 29

Mongolian gerbils are epilepsy-prone animals. In adult gerbils two major groups can be differentiated according to their seizure behavior: Highly seizure-sensitive gerbils exhibit facial and forelimb clonus or generalized tonic-clonic seizures from the first test on, while kindled-like gerbils are seizure free for the first three to six consecutive tests, later develop forelimb myoclonus, and eventually progress to generalized tonic-clonic seizures. In the hippocampus, seizure history of the individual animal is mirrored in the intensity in which GABAergic neurons are immunostained for the calcium-binding protein parvalbumin: they lose parvalbumin with increasing seizure incidence. In a first step to clarify the influence of hippocampal projection neurons on spontaneous seizure behavior and related parvalbumin expression, we induced degeneration of the CA1 pyramidal cells by transient forebrain ischemia. This results in a decreased seizure sensitivity in highly seizure-sensitive gerbils. The kindling-like process, however, is not permanently blocked by the ischemic nerve cell loss, suggesting that an intact CA1 field is not a prerequisite for the development of seizure behavior. The seizure-induced loss of parvalbumin from the ischemia-resistant interneurons recovers after ischemia. Thus, changes in parvalbumin content brought about by repeated seizures are not permanent but can rather be modulated by novel stimuli.
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PMID:Ischemia-induced degeneration of CA1 pyramidal cells decreases seizure severity in a subgroup of epileptic gerbils and affects parvalbumin immunoreactivity of CA1 interneurons. 1125 24

Sex differences in sensitivity to seizures elicited by intraperitoneally injected pentylenetetrazol (PTZ) were studied in 240 (120 males and 120 females) adult Swiss mice. Animals were separated into four groups according to the dose that was injected: 40, 50, 60 and 70 mg/kg. Seizure severity was expressed by the following scoring scale: (0) no abnormal behavior; (1) myoclonus; (2) running bouncing (RB) clonus; (3) tonic hind limb extension (THE). The analyses of the dose-response curves indicated that females were more susceptible than males when the 50- and 60-mg/kg doses were used. Specifically, females often displayed RB clonus, while males frequently displayed only myoclonus or no abnormal behavior. No significant sex differences were demonstrated when either the 40- or the 70-mg/kg doses were used. These data indicate that, for a specific range of doses, sex differences in seizure susceptibility can be clearly demonstrated with the use of intraperitoneally injected PTZ. In this sense, this method could be used as a tool to investigate the role played by sexual hormones in regulating the sensitivity of the gamma-aminobutiric acid (GABA(A)) receptor complex (GRC).
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PMID:Sex differences in sensitivity to seizures elicited by pentylenetetrazol in mice. 1132 16

The effects of callosal agenesis in sensitivity to pentylenetetrazol (PTZ) were studied in 199 (95 males and 104 females) mice of the BALB/cCF strain. This strain presents agenesis of the corpus callosum (CC) in approximately 30% of its population. Seizures were elicited by intraperitoneally injected PTZ. Animals were tested with doses of 40 and 50 mg/kg. Seizure severity was expressed by the following scoring scale: 0 (no abnormal behavior, NAB); 1 (myoclonus, M); 2 (running bouncing clonus, RBC); 3 (tonic hindlimb extension, THE). For the 40-mg/kg dose, abnormal mice were found to be more susceptible, displaying more severe seizures more often then normal mice. Normal female mice were also more susceptible to PTZ than males for this dose. No significant differences were found for the 50-mg/kg dose as a result of the fact that most animals displayed RBC. These data indicate that callosal development and sex are important factors affecting seizure susceptibility.
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PMID:The effects of callosal agenesis on the susceptibility to seizures elicited by pentylenetetrazol in BALB/cCF mice. 1181 12

We studied the occurrence of small-amplitude myo- clonus in 20 idiopathic Parkinson's disease patients who had no evidence of dementia as defined by criteria in the Diagnostic and Statistical Manual of Mental Disorders, fourth edition. Parkinson's disease was diagnosed by United Kingdom Brain Bank criteria, and clinical assessment was performed with the Unified Parkinson's Disease Rating Scale motor score, Hoehn and Yahr staging, and the Mini-Mental State Examination. Clinical assessment showed a range of mild-to-moderate disease severity. All patients underwent polygraphic electro-encephalographic-electromyographic (EMG) recording with back-averaging, somatosensory evoked potential testing, and attempted elicitation of long-latency EMG responses. Multichannel surface EMG recording during muscle activation showed irregular, multifocal, brief (<50 msec) myoclonus EMG discharges. Back-averaging consistently showed a focal, short-latency, electroencephalographic transient prior to the myoclonus EMG discharge. Cortical somatosensory evoked potential waves were not enlarged, and long-latency EMG responses at rest were not present. The small-amplitude myoclonus in such cases arises from an abnormal discharge from the sensorimotor cortex. The mechanism of this cortical myoclonus in Parkinson's disease has differences from the more common "cortical reflex myoclonus" physiology. Advanced parkinsonism is not a requirement for manifestation of this myoclonus type. Although the myoclonus occurred without dementia in these cases, its relationship to the subsequent development of cognitive impairment remains to be defined.
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PMID:Small-amplitude cortical myoclonus in Parkinson's disease: physiology and clinical observations. 1221 Aug 53

Excess serotonin in the central nervous system leads to a condition commonly referred to as the serotonin syndrome, but better described as a spectrum of toxicity - serotonin toxicity. Serotonin toxicity is characterised by neuromuscular excitation (clonus, hyperreflexia, myoclonus, rigidity), autonomic stimulation (hyperthermia, tachycardia, diaphoresis, tremor, flushing) and changed mental state (anxiety, agitation, confusion). Serotonin toxicity can be: mild (serotonergic features that may or may not concern the patient); moderate (toxicity which causes significant distress and deserves treatment, but is not life-threatening); or severe (a medical emergency characterised by rapid onset of severe hyperthermia, muscle rigidity and multiple organ failure). Diagnosis of serotonin toxicity is often made on the basis of the presence of at least three of Sternbach's 10 clinical features. However, these features have very low specificity. The Hunter Serotonin Toxicity Criteria use a smaller, more specific set of clinical features for diagnosis, including clonus, which has been found to be more specific to serotonin toxicity. There are several drug mechanisms that cause excess serotonin, but severe serotonin toxicity only occurs with combinations of drugs acting at different sites, most commonly including a monoamine oxidase inhibitor and a serotonin reuptake inhibitor. Less severe toxicity occurs with other combinations, overdoses and even single-drug therapy in susceptible individuals. Treatment should focus on cessation of the serotonergic medication and supportive care. Some antiserotonergic agents have been used in clinical practice, but the preferred agent, dose and indications are not well defined.
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PMID:Serotonin toxicity: a practical approach to diagnosis and treatment. 1787 86

This paper reviews the main neurological complications of psychiatric drugs, in particular antipsychotics and antidepressants. Extrapyramidal syndromes include acute dystonia, parkinsonism, akathisia, tardive dyskinesia and tardive dystonia. Extrapyramidal symptoms (EPS) are less frequent with atypical than with conventional antipsychotics but remain common in clinical practice partly due to lack of screening by health professionals. Neuroleptic malignant syndrome (NMS) consists of severe muscle rigidity, pyrexia, change in conscious level and autonomic disturbance but partial forms also occur. NMS is particularly associated with the initiation and rapid increase in dose of high-potency antipsychotics but it has been reported with all the atypical antipsychotics and rarely with other drugs including antidepressants. Serotonin toxicity comprises altered mental state (agitation, excitement, confusion), neuromuscular hyperactivity (tremor, clonus, myoclonus, hyper-reflexia) and autonomic hyperactivity and occurs on a spectrum. Severe cases, termed serotonin syndrome, usually follow the co-prescription of drugs that increase serotonergic transmission by different pathways, for example a monoamine oxidase inhibitor (MAOI) and a selective serotonin reuptake inhibitor (SSRI). Most antipsychotics and antidepressants lower the seizure threshold and can cause seizures; the risk is greater with clozapine than with other atypical antipsychotics and greater with tricyclic antidepressants (TCAs) than with SSRIs. In randomised controlled trials in elderly patients with dementia atypical antipsychotics are associated with a higher risk of stroke and death than placebo. Cohort studies suggest that conventional drugs carry at least the same risk. Cessation of treatment with antipsychotics and antidepressants can lead to a wide range of discontinuation symptoms which include movement disorders and other neurological symptoms. Clinicians need to be familiar with strategies to reduce the risk of these adverse events and to manage them when they arise. Their occurrence needs to be balanced against the benefits of psychiatric drugs in terms of efficacy and improved quality of life in a range of disorders.
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PMID:Neurological complications of psychiatric drugs: clinical features and management. 1809 17


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