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)

A family is described with three affected brothers, two of whom were examined, born to consanguineous parent, who in early adult life began to experience ataxia, intention myoclonus, and progressive visual failure. The brothers examined had cherry red spots at the maculae and cataracts. They were of normal intelligence. The intention myoclonus responded partially to treatment with clonazepam and pheneturide, but not to 5-hydroxytryptophan in combination with carbidopa or to sodium valproate. Studies in one patient showed the excretion of large quantities of sialylated oligosaccharides in the urine. Both patients showed deficient sialidase activity in their cultured fibroblasts. Further studies on cultured skin fibroblasts revealed increased electrophoretic mobility of six glycoprotein enzymes that was returned approximately to normal by treatment with sialidase. The clinical and biochemical findings indicate that these patients are further cases of the newly described condition sialidosis type 1.
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PMID:Sialidosis type 1: cherry red spot-myoclonus syndrome with sialidase deficiency and altered electrophoretic mobilities of some enzymes known to be glycoproteins. 1. Clinical findings. 51 62

Biochemical studies of serotonin metabolism and a therapeutic trial of L-5-hydroxytryptophan (L-5-HTP) in combination with carbidopa were carried out in 19 patients with myoclonus. In 6 patients with intention myoclonus, the cerebrospinal fluid concentration of 5-hydroxyindoleacetic acid, a metabolite of serotonin was found to be significantly decreased. L-5-HTP with carbidopa dramatically decreased the frequency and intensity of myoclonus, particularly in those patients with a diagnosis of postanoxic intention myoclonus. The major side effects have been anorexia, nausea, vomiting, diarrhea and mental stimulation. We suggest that a deficiency of brain serotonin is causally related to myoclonic muscle movements and the therapeutic efficacy of L-5-HTP plus carbidopa may be due to the repletion of serotonin in regions of the brain where serotoninergic neurons have degenerated.
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PMID:Serotonin and myoclonus. 79 Jan 70

Three patients with postanoxic intention myoclonus, two patients with intention tremor, and one patient with cerebral palsy were administered L-5-hydroxytryptophan (L-5HTP), the precursor of serotonin, in combination with MK 486, a peripheral amino acid decarboxylase inhibitor. L-5HTP combined with MK 486 were potent long-term therapeutic agents for postanoxic intention myoclonus, but had no effect on intention tremor or cerebral palsy. These drugs were well-tolerated by the patients, and more effective than any other known therapy for intention myoclonus. Cerebrospinal fluid concentration of 5-hydroxyindoleacetic acid, the main catabolite of serotonin, appeared low in two patients with intention myoclonus and increased markedly during drug therapy. Postanoxic intention myoclonus may be causally related to a deficiency of brain serotonin.
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PMID:Therapy of intention myoclonus with L-5-hydroxytryptophan and a peripheral decarboxylase inhibitor, MK 486. 107 20

A myoclonic syndrome consisting of tremor, myoclonus, and seizures was produced following the systemic administration of 5-hydroxytryptophan to adult rats previously given intracisternal injections of 5,7-dihydroxytryptamine and systemic desmethylimipramine, but not in their controls. This behavioral response was blocked by pretreatment with the putative serotonin receptor blocking agents methysergide, lysergic acid diethylamide, and bromolysergic and diethylamide, as well as centrally effective doses of the aromatic amino acid decarboxylase inhibitor Ro4-4602. Blockers of receptors of other neurotransmitters had little effect. This neurologic response in the adult rat may be relevant to some forms of clinical myoclonus and may be useful in testing potential agonists and antagonists of serotonin receptors in the mammalian central nervous system.
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PMID:Myoclonus after 5-hydroxytryptophan in rats with lesions of indoleamine neurons in the central nervous system. 108 96

In two patients with postanoxic action myoclonus, L-tryptophan or a monoamine oxidase inhibitor induced a moderate improvement, but L-5-hydroxytryptophan had greater therapeutic effect. Methysergide, a potent blocker of serotonin receptors, consistently induced a marked deterioration in myoclonus. Pretreatment cerebrospinal fluid 5-hydroxyindoleacetic acid levels were reduced significantly in both patients. These findings suggest that postanoxic action myoclonus likely is associated with insufficient serotonergic activity in the central nervous system. Data are inadequate to determine whether this apparent insufficiency reflects structural changes in 5HT-containing raphe nuclei due to a direct anoxic damage to these structures of functional changes caused by a secondary reduction in the activity of intact serotonergic neurons.
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PMID:Beneficial effects of serotonin precursors in postanoxic action myoclonus. 108 68

The serotonin precursor L-5-hydroxytryptophan is useful therapy for patients with posthypoxic intention myoclonus. L-5-hydroxytryptophan plus carbidopa was administered to eight patients with this disorder or other syndromes in which myoclonus is prominent. This treatment (1) decreased the frequency of occurrence and amplitude of intention myoclonus in two patients with posthypoxic intention myoclonus and in one with idiopathic myoclonus, (2) had no effect in one patient with congenital encephalopathy and myoclonus, and (3) increased the frequency of occurrence and amplitude of myoclonus in two patients with lipid storage disease, one with myoclonic epilepsy, and in an additional patient with idiopathic myoclonus. Therefore, L-5-hydroxytryptophan does not effect improvement in all forms of myoclonus; it should be given with caution because it produces a high incidence of side effects. A patient's response to L-5-hydroxytryptophan therapy may be important in a diagnostic classification of myoclonic syndromes based on differences in indoleamine neurotransmitter function.
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PMID:L-5-hydroxytryptophan in treatment of several different syndromes in which myoclonus is prominent. 108 88

While the 5-HT precursors tryptophan and 1-5-HTP cause an increase in serum prolactin concentration, a combination of 1-5-HTP with a peripheral decarboxylase inhibitor was found to reduce the serum prolactin concentration. This combination seemed to behave like a DA agonist. This effect is not produced by the decarboxylase inhibitor per se. A possible explanation is that 5-HTP is converted to 5-HT in CA-ergic neurons, that 5-HT supersedes the CA from the stores, and that some of the CA reach the synaptic cleft and stimulate CA receptors. Another possible explanation is that 5-HTP decarboxylase is centrally inhibited as well, and that an effect of 5-HTP itself is involved here. In view of the observations made it is doubtful whether the therapeutic effect of 5-HTP combined with a peripheral decarboxylase inhibitor in depressions and myoclonus can in fact be atributed to activation of central serotonergic systems.
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PMID:An unexpected effect of L-5 hydroxytryptophan-ethyl-ester combined with a peripheral decarboxylase inhibitor on human serum prolactin. 108 2

The excitability cycles of the N1-P1-N2 waveforms of the scalp-recorded somatosensory evoked potential (SEP) and of the long-latency, cortical loop reflex electromyographic (EMG) activity were studied in two patients with cortical reflex myoclonus. Long-latency cortical loop reflex EMG activity in the thenar muscles and giant SEPs occurred following median nerve stimulation. The excitability cycle of the EMG paralleled that of the SEP. There was an initial period of attenuation of SEP and EMG amplitude at interstimulus intervals (ISIs) of less than 40 ms followed by a period of amplitude enhancement at an ISI of up to 200 ms followed by a second period of attenuation. The excitability cycle is abnormal and the SEP and EMG amplitude changes parallel each other. It is therefore likely that a common mechanism determines the abnormal excitability cycle. The substrate for this mechanism is unknown and may be diffuse or restricted. Oral 5-hydroxytryptophan (5-HTP) in therapeutic doses altered the SEP excitability cycle. 5-HTP did not attenuate the giant SEPs but did attenuate the long-latency reflex EMG. Therefore, 5-HTP's site of action may be different from the substrate underlying the mechanism that results in the giant SEPs. Additionally, spinal latency reflex EMG activity occurred following treatment with 5-HTP but was absent when the patient discontinued 5-HTP.
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PMID:Cortical reflex myoclonus. A study of the relationship between giant somatosensory evoked potentials and motor excitability. 190 37

We describe a 37-year-old man with spinal segmental myoclonus characterized by symmetric, rhythmic contractions of the abdomen with a frequency ranging between 100 and 150/min. The combination of sodium valproate and L-5-hydroxytryptophan was useful to control the myoclonus. We comment on the possible role of the serotonergic system in this syndrome.
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PMID:Spinal myoclonus: successful treatment with the combination of sodium valproate and L-5-hydroxytryptophan. 201 15

To study the involvement of serotonin (5-HT) receptor subtypes in behavioral supersensitivity following neonatal 5,7-dihydroxytryptamine (5,7-DHT) lesions, we measured acute behavioral responses to a single dose of selective 5-HT1A (8-OH-DPAT) or 5-HT2,1C (DOI) agonist compared to 5-hydroxytryptophan (5-HTP) in rats injected with 5,7-DHT intraperitoneally or intracisternally 14 weeks earlier. Only intraperitoneal 5,7-DHT injection resulted in brainstem 5-HT hyperinnervation, but cortical 5-HT depletions were also less. Effects of DOI, such as shaking behavior and forepaw myoclonus, were enhanced by 5,7-DHT lesions made intracisternally not intraperitoneally, whereas 8-OH-DPAT-evoked behaviors, such as forepaw myoclonus and head weaving, were enhanced more by the intraperitoneal route. The main consequence of intraperitoneal compared to intracisternal 5,7-DHT injection on supersensitivity to 5-HT agonists was increased presynaptic 5-HT1A responses and decreased 5-HT2,1C responses. In contrast, 5-HTP evoked more shaking behavior and less of the serotonin syndrome with the intraperitoneal compared to the intracisternal route of 5,7-DHT injection. Behavioral supersensitivity to 5-HTP, which was attributable to 5-HT1A, 5-HT2,1C, and possibly to other 5-HT receptors, was orders of magnitude greater than that elicited by direct receptor agonists and more clearly differentiated between rats with 5,7-DHT lesions and their controls, and between routes of 5,7-DHT injections, than responses to 5-HT agonists at the dose studied. 5,7-DHT induced dysregulation of 5-HT receptors, including both presynaptic and postsynaptic changes and altered interactions between receptor subtypes, better explains these data than postsynaptic changes alone.
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PMID:The functional significance of neonatal 5,7-dihydroxytryptamine lesions in the rat: response to selective 5-HT1A and 5-HT2,1C agonists. 214 15


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