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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:The serotonin hypothesis of myoclonus from the perspective of neuronal rhythmicity. 1196 57

Despite the great progress of psychiatry, many of its fundamental problems remain unresolved. Obviously, new ideas that expand the present understanding of such problems are useful. In this paper, the following hypothesis is proposed: mental disorders are caused by hypoxic phenomena, stimulating hypertrophied growth of a neural network; treatment should be directed towards the damaging of abnormal elements of this network; successful treatment is inevitably accompanied by moderate retrograde amnesia. Based on this hypothesis, the connection between etiology, pathogenesis, and therapy of mental disorders is described, the role of retrograde amnesia is shown, and potential new methods of treatment (shaking, vibration, and ultrasound) are predicted. To test the hypothesis, some means are discussed. The first means is based on the analysis of the reasons of unsuccessful clinical trials of the method of mental disorders treatment by acute hypoxic hypoxia (USA, 1938-1940). Such a method, according to the hypothesis, should damage the abnormal elements of a neural network as a result of acute hypoxia. Analysis of the equipment and procedure shows that the trials were unsuccessful as a result of insufficiently powerful hypoxic influence. Improvements to this method are proposed. When using this method, it is advisable to measure the cerebral blood oxygenation index and reduce it by regulating the oxygen concentration in the hypoxic gas mixture given to the patient. This reduction should continue until the patient reaches a state of moderate retrograde amnesia. It is also advisable to note the blood oxygenation index value at the moment when the patient lapses into unconsciousness, and then, on the basis of this value, estimate a necessary power (i.e., acuteness and duration) of hypoxic hypoxia. Other means for testing the hypothesis are also discussed: retrospective analysis of the results of electroconvulsive therapy, and testing the predicted methods of treatment.
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PMID:Recovering at the cost of amnesia? 1851 Dec 11