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Biomedical subjects

C D Marsden

Publications and source records attributed to C D Marsden.

At least 649 records · Page 36Linked to original sources
PubMed1986

Electrophysiological and positron emission studies in a patient with cortical myoclonus, epilepsia partialis continua and motor epilepsy.

A patient is described who had a combination of stimulus-sensitive cortical myoclonus, epilepsia partialis continua, and Jacksonian motor epilepsy. He eventually required surgery because of the severity of his seizures. Electrophysiological recordings made before and during surgery, and PET scans performed before surgery identified an abnormal area of cerebral cortex in the postcentral parietal region. It is suggested that the stimulus-sensitive myoclonus arose because input into this region from peripheral sensory afferents produced an abnormal discharge which was fed forwards via cortico-cortical connections to the precentral motor cortex, to produce a reflex muscle jerk. The epilepsia partialis continua may have been caused by spontaneous discharges arising in the same region of parietal cortex. Both forms of jerking disappeared after resection of this part of the cortex.

Adult↗
PubMed1986

Brain dopamine metabolism in patients with Parkinson's disease measured with positron emission tomography.

L-[18F] fluorodopa was administered in trace amounts intravenously to healthy control subjects and to patients with Parkinson's disease. Striatal uptake of radioactivity was measured using positron emission tomography. The capacity of the striatum to retain tracer was severely impaired in patients compared to controls. This may reflect a reduction of striatal dopamine storage in Parkinson's disease. Patients showing the "on/off" phenomenon had an even greater decrease of striatal storage capacity.

Adult↗
PubMed1986

Dystonia of the legs induced by walking or passive movement of the big toe in a patient with cerebellar ectopia and syringomyelia.

A 45-year-old man with dystonia of the legs was found to have cerebellar ectopia and syringomyelia. Both walking and passive movements of the big toes evoked dystonic postures of the legs. Electrophysiologic studies suggested that the dystonic movements were reflex in origin. We propose that the cervical spinal cord lesion, involving propriospinal pathways, resulted in an abnormal response of spinal interneurons to peripheral stimuli.

Cerebellar Diseases↗
PubMed1986

Torsion dystonia: a double-blind, prospective trial of high-dosage trihexyphenidyl.

We studied trihexyphenidyl in the treatment of torsion dystonia in a prospective, double-blind crossover protocol. Thirty-one patients completed the protocol. Twenty-two (71%) had a clinically significant response. After a mean follow-up of 2.4 years, 68% of patients continued to take trihexyphenidyl, and 42% continued to show a considerable or dramatic benefit. The 30-mg dose used was generally well tolerated. High-dosage trihexyphenidyl therapy is effective in the management of torsion dystonia.

Adolescent↗
PubMed1986

5-HT-mediated myoclonus in the guinea pig as a model of brainstem 5-HT and tryptamine receptor action.

Indoleamine-induced myoclonus in guinea pigs is a specific model of brainstem 5-HT function that can be used to characterize the indoleamine systems initiating myoclonus. 5-HT precursors and indole-containing 5-HT agonists induce myoclonus in guinea pigs, but piperazine-containing compounds do not. This selectivity of action correlates with the ability of 5-HT agonists to act at 5-HT-1 receptors. Further evidence for the involvement of a brainstem 5-HT receptor subpopulation in the initiation of myoclonus is shown by the differential ability of 5-HT antagonists to inhibit 5-HTP-induced myoclonus and of 5-HT reuptake blockers to potentiate threshold myoclonus. Distinct tryptamine receptors also may be involved in producing myoclonus, since indoleamine antagonists show differing potencies in inhibiting 5-HTP- and tryptamine-induced myoclonus. Tryptamine-induced myoclonus is, however, dependent on intact presynaptic 5-HT function. Biochemical studies indicate that 5-HT is primarily responsible for 5-HTP-evoked myoclonus, whereas tryptamine predominates in tryptamine-induced myoclonus. Both 5-HT and tryptamine may contribute to myoclonus produced by L-tryptophan. Indoleamine-induced myoclonus in guinea pigs may be valuable in studying the organization of brainstem indoleamine systems that may be involved in some forms of human myoclonus.

5-Hydroxytryptophan↗
PubMed1986

p,p'-DDT-induced myoclonus in the rat and its application as an animal model of 5-HT-sensitive action myoclonus.

p,p'-DDT-induced myoclonus in mice has been proposed as a model of stimulus-sensitive action myoclonus responsive to L-5-HTP and clonazepam treatment. However, we have been unable to confirm the ability of clonazepam to reduce myoclonus induced by p,p'-DDT in the rat. A detailed pharmacological, biochemical, and physiological investigation in the latter species shows p,p'-DDT-induced myoclonus not to resemble stimulus-sensitive action myoclonus occurring in humans. Precursors of 5-HT (L-tryptophan and L-5-HTP) reduced the intensity of myoclonus, but the 5-HT agonists quipazine and Org 6582 did not. 5-HT antagonists (methergoline, methysergide, and cinanserin) did not potentiate myoclonus induced by p,p'-DDT. In contrast, administration of MAOIs (pargyline, nialamide, and tranylcypromine) markedly attenuated the myoclonus. No observable changes in cerebral 5-HT biochemical parameters occurred at the onset of myoclonus, although brain tryptophan and 5-HIAA were increased following periods of prolonged myoclonus. Electrophysiological analysis of p,p'-DDT-induced myoclonus in the rat revealed changes in EEG and EMG activity that were different from those observed in human reticular reflex myoclonus. In conclusion, in contrast to the mouse, myoclonus induced by p,p'-DDT in the rat does not appear to be a suitable model of 5-HT-sensitive action myoclonus in man.

5-Hydroxytryptophan↗
PubMed1986

Mechanism of action of clonazepam in myoclonus in relation to effects on GABA and 5-HT.

Clonazepam is a potent anticonvulsant 1,4-benzodiazepine that controls some types of myoclonus. Its primary mode of action is to facilitate GABAergic transmission in the brain by a direct effect on benzodiazepine receptors. GABA receptors lie on the cell bodies of dorsal raphe neurons, and GABA acts to inhibit raphe cell firing, an action potentiated by benzodiazepines. Clonazepam does not alter 5-HT synthesis but decreases 5-HT utilization in brain and blocks the egress of 5-HIAA from the brain. It is not known whether the actions of clonazepam in altering 5-HT function are responsible for its antimyoclonic action, since these are observed only after large doses. Also, the effects of clonazepam are the exact opposite of those predicted from the beneficial effects of 5-HTP in human myoclonic disorders. Finally, why clonazepam, more than other benzodiazepines, is of benefit in the treatment of myoclonus is not clear. This may be due to some pharmacokinetic feature of the drug in conjunction with its potency at benzodiazepine receptors.

5-Hydroxytryptophan↗
PubMed1986

The thermodynamics of agonist and antagonist binding to dopamine D-2 receptors.

The ability of dopamine agonists and antagonists to compete with [3H]spiperone binding to rat striatal membrane preparations at 4, 15, 26, and 37 degrees varied markedly with temperature. Dopamine and the dopamine agonist 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide (ADTN) were more potent at lower temperatures. The ability of the dopamine antagonists, haloperidol, cis-flupenthixol, cis-N-(1-benzyl-1-methypyrrolidin-3-yl)-5-chloro-2-methoxy-9- methylaminobenzamide (YM 09151-2), raclopride, and clozapine, and of the agonists apomorphine and pergolide, to compete with [3H]spiperone binding was little altered by temperature. (+)-Butaclamol was more potent at higher temperatures. In contrast, the antagonists sulpiride, metoclopramide, clebopride, sultopride, tiapride, piquindone, and zetidoline were more potent at lower temperatures. The interaction of the agonists dopamine and ADTN was driven by a decrease in enthalpy, allowing an energetically unfavorable decrease in entropy. The binding of the antagonists, haloperidol, cis-flupenthixol, YM 09151-2, raclopride, (+)-butaclamol, and clozapine, and also of the agonists, apomorphine and pergolide, was entropy driven. The interaction of the antagonists sulpiride, metoclopramide, clebopride, alizapride, sultopride, tiapride, piquindone, and zetidoline differed from that of other antagonists in being enthalpy driven. The observed entropy changes correlated with the lipophilicity of the displacing drugs and not with their intrinsic activity.

Animals↗
PubMed1986

The actions of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in animals as a model of Parkinson's disease.

The ability of MPTP to induce persistent parkinsonism in man may provide a vital clue to the cause of the idiopathic disease. However, the peripheral administration of MPTP to rodent species only produces losses in brain dopamine content and damage to the nigrostriatal system in high doses and no persistent motor deficits have been observed. In contrast, in primates, the administration of MPTP rapidly induces a persistent parkinsonian syndrome accompanied by evidence for selective damage to the nigro-striatal dopamine containing system. Other neurotransmitter systems appear unaffected by MPTP treatment. The MPTP-treated primate responds to the administration of L-DOPA and other antiparkinsonian drugs and may provide a useful test-bed for the development of novel antiparkinsonian medication. Administration of MPTP to primates causes an accumulation of MPP+ in a variety of brain areas. The accumulation of MPP+ and the neurotoxic actions of MPTP in primates can be prevented by the prior administration of monoamine oxidase inhibitors. The ability of monoamine oxidase inhibitors to prevent MPTP toxicity is related to the metabolism of MPTP by monoamine oxidase B, probably extraneuronally in glia, to produce MPDP+ and subsequently MPP+. In rodent synaptosomal preparations MPP+ is a substrate for the dopamine uptake mechanism and so would be selectively accumulated in brain dopamine neurones. Administration of MPTP to animals results in the production of a partial model of idiopathic Parkinson's disease as it occurs in man. MPTP treatment produces the major symptoms of Parkinson's disease in primates but the pathology is limited to the nigro-striatal system, whereas in Parkinson's disease pathology is more widespread. Biochemical changes induced by MPTP again seem primarily limited to those induced by damage to the nigro-striatal dopamine containing system. MPP+ (or another metabolite of MPTP) may be responsible for the neurotoxicity of MPTP but not all neurones which accumulate products of MPTP metabolism are damaged. The nigro-striatal system may be peculiarly sensitive to the effects of MPTP.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

Affinity of pyridylalkylamines for nicotinic, muscarinic and histaminic recognition sites in brain tissue preparations.

The affinity of 15 regioisomeric and homologous pyridylalkylamines was examined in brain preparations for nicotinic, muscarinic, and H1-histaminic binding sites as labeled by [3H]-nicotine, [3H]-dexetimide and [3H]-mepyramine, respectively. Overall, the compounds show a clear selectivity for the nicotinic versus muscarinic binding sites, and a weak affinity for the H1-histaminic sites. Variations in affinity appear to be partly influenced by steric factors (such as position of attachment, length and rigidity of side-chain) and marginally by lipophilicity.

Amines↗
PubMed1986

Toxic myoclonus.

Several toxins produce encephalopathies in which myoclonus can be a prominent feature. These include intoxications with bismuth, methyl bromide, cooking oil containing anilines, and tetraethyl lead. The clinical features in many cases resemble the action myoclonus syndrome of posthypoxic encephalopathy.

Bismuth↗