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Biomedical subjects

C D Marsden

Publications and source records attributed to C D Marsden.

At least 433 records · Page 24Linked to original sources
PubMed1990

Movement disorders in mitochondrial myopathies. A study of nine cases with two autopsy studies.

Of 85 consecutive patients with mitochondrial myopathy, 29 had clinically significant central nervous system involvement. Nine of these had movement disorders that included dystonia, chorea, parkinsonism, and myoclonus. Autopsy studies of one patient with ataxia, dementia, and parkinsonism followed by dystonia showed the features of olivopontocerebellar atrophy with additional degenerative changes in the basal ganglia. Postmortem in a further case with myoclonus, deafness, muscle weakness, retinopathy, and ataxia showed symmetrical mineralisation of the striatopallidodentatal system.

Adult↗
PubMed1990

Mitochondrial DNA analysis in Parkinson's disease.

The reduced form of nicotinamide adenine dinucleotide coenzyme Q reductase (complex I) activity has recently been shown to be deficient in the substantia nigra of patients dying with Parkinson's disease. This biochemical defect is identical to that produced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which also produces parkinsonism in humans. Complex I comprises 25 polypeptides, seven of which are encoded by mitochondrial DNA. Restriction fragment analysis of substantia nigra DNA from six patients with Parkinson's disease did not show any major deletion. In two cases, there were different novel polymorphisms that were not observed in control brain (n = 6) or blood (n = 34) samples.

DNA Damage↗
PubMed1990

Differential ability of selective and non-selective dopamine agonists to induce climbing in the rat indicates the involvement of both D-1 and D-2 receptors in this behaviour.

Approximately 50% of female Wistar rats examined exhibited a continuous climbing response to a screening dose of apomorphine. In animals identified as climbing, the mixed D-1/D-2 agonists apomorphine, pergolide and L-dopa, and the indirectly acting agonists nomifensine and (+)-amphetamine, induced a dose-related climbing response. The selective D-1 agonist SKF 38393 caused only minimal climbing, and the selective D-2 agonists bromocriptine, lisuride and LY 141865 induced a weak climbing response. All agonists examined, except SKF 38393, caused a dose-related stereotypy response. The selective D-1 antagonist SCH 23390, and the selective D-2 antagonist sulpiride, both produced maximum inhibition of apomorphine-induced climbing. SCH 23390 also inhibited stereotyped behaviour, but sulpiride was less effective. In animals identified as "non-climbers" using the screening dose of apomorphine, only L-dopa induced a marked climbing response. Nomifensine and bromocriptine produced weak or discontinuous climbing in this group, while the other agonists examined had little or no effect. In contrast all drugs examined, except SKF 38393, induced stereotyped behaviour of the same intensity observed in the "climbers". It is concluded that stimulation of both D-1 and D-2 receptors is necessary to induce a continuous climbing behaviour in rats. D-2, but not D-1 stimulation, alone can induce a weak or discontinuous climbing response, but concomitant stimulation of D-1 receptors potentiates this effect. Failure of some rats to climb does not appear to be related to relative degrees of D-1 and D-2 stimulation.

Amphetamine↗
PubMed1990

Prism adaptation and other tasks involving spatial abilities in patients with Parkinson's disease, patients with frontal lobe lesions and patients with unilateral temporal lobectomies.

Patients in the early stages of Parkinson's disease were compared with patients who had sustained damage specific to either the frontal or temporal lobes and normal controls on a delayed alternation task, a test of the left right orientation and a prism adaptation task. On the former two tasks age accounted for more of the variability in performance than did site of brain lesion. However, patients with frontal lobe, right temporal lobe or basal ganglia damage were significantly impaired on the adaptation task. The results are discussed with regard to "switching", "sequencing" and "internal guidance" of movement hypotheses.

Adult↗
PubMed1990

Writer's cramp.

Writer's cramp has been recognized for over a century, and originally was construed as a physical motor disorder. However, an unfortunate use of the descriptive term 'professional neuroses' to describe this and other similar task-specific conditions, coupled subsequently with fashions in psychiatry, led to the mistaken belief that writer's cramp was due to psychic rather than motor pathology. Evidence has accumulated in recent years showing that writer's cramp is a real focal motor disorder, with a close relation to dystonia. This article summarizes what is known about the aetiology, clinical features, pathophysiology and treatment of writer's cramp and analogous occupational cramps, with the aim of drawing the attention of neuroscientists to this common, bizarre and poorly understood condition.

Female↗
PubMed1990

Cognitive function in Parkinson's disease: from description to theory.

From the large body of empirical evidence on cognitive function in Parkinson's disease, a number of attempts have been made to describe the characteristics of the deficits and the conditions under which they are observed. This review considers descriptions limited to specific domains of cognition such as visuospatial function, memory and 'frontal' function, and more general descriptions relating to 'set-shifting', sequencing, temporal ordering and recency discrimination, the locus of cognitive control and bradyphrenia. Later in the paper an attempt is made to provide some theoretical framework for the various descriptions. Two theories are discussed representing contrasting, but complementary approaches. The first is a 'psychological' theory in which the concept of depleted processing resources is suggested as a possible mechanism to explain the observable deficits. The second is a neurobiological model that attempts to integrate information from diverse sources to provide a model for the neuroanatomical and neurochemical substrate that may underlie some of the behavioural deficits.

Caudate Nucleus↗
PubMed1990

Increased [Met]enkephalin and decreased substance P in spinal cord following thermal injury to one limb.

Thermal injury to one hind limb of rats was induced by immersion into water at 62 degrees C. Both a mild (15 s) or severe (30 s) lesion caused inflammation of the limb when observed 24 h later; but at this time the animals used the injured limb when they walked. Animals with a severe lesion of the injured limb subsequently withdrew it from use when walking. Limb withdrawal did not occur following a mild lesion. At 24 h following the lesion, lumbar spinal cord levels of [Met]enkephalin, as measured by radioimmunoassay, were elevated (70%) bilaterally in both hemisegments, ipsi- and contralateral to the lesion. At seven days following either mild or severe hind limb lesion [Met]enkephalin levels were elevated only in the ipsilateral lumbar hemisegment. At that time no changes in thoracic [Met]enkephalin levels were observed. Substance P levels were decreased (20-25%) bilaterally in the lumbar cord 24 h following a severe limb lesion, but no change was observed at seven days in any cord segment following a mild or severe lesion. Changes in spinal cord [Met]enkephalin content occur in response to thermal injury to one hind limb. However, the changes do not appear to be related to the withdrawal of the damaged limb from use following a severe lesion. Peptide changes in the spinal cord may reflect pain or injury to the damaged limb following a thermal lesion. In contrast, limb withdrawal may be a physiological rest mechanism related to altered basal ganglia peptide function.

Animals↗
PubMed1990

A genetic study of idiopathic torsion dystonia in the United Kingdom.

The inheritance of idiopathic torsion dystonia (ITD) was investigated in 100 British families containing 107 index cases with generalized, multifocal or segmental dystonia, and 79 secondary cases. Fifty-eight index cases had affected relatives, usually in two or more generations. Nearly half of the secondary cases were asymptomatic. Paternal age was increased among the 49 single cases, parental consanguinity was not increased and there was no evidence of genetic heterogeneity. Eleven cases (10.3%) were Jewish, which exceeded the number expected, but they did not differ clinically or genetically from non-Jewish cases. The most likely explanation for the excess of Jewish cases is a founder effect in Eastern Europe. We conclude that, in the UK, approximately 85% of cases of ITD are due to an autosomal dominant gene with about 40% penetrance and highly variable expression, possibly reflecting environmental influences. Approximately 14% of these inherited cases may represent new mutations. The remaining 15% are probably nongenetic phenocopies, but are not clinically distinguishable. There was no evidence in this study for the existence of autosomal recessive or X-linked forms of ITD. The estimated recurrence risk for first degree relatives of familial cases is 21%; the risk is lower for single cases. Of affected individuals, 75% will have developed symptoms or signs of dystonia by the age of 30 yrs.

Adolescent↗
PubMed1990

The relationship between locomotor disability, autonomic dysfunction, and the integrity of the striatal dopaminergic system in patients with multiple system atrophy, pure autonomic failure, and Parkinson's disease, studied with PET.

18F-dopa and S-11C-nomifensine (NMF) are positron emitting tracers whose caudate and putamen uptake reflects striatal dopamine storage capacity and the integrity of dopamine reuptake sites, respectively. Using these two tracers, the integrity of the presynaptic striatal dopaminergic system has been studied with positron emission tomography (PET) in 10 subjects with multiple system atrophy (MSA, Shy-Drager syndrome) who had an akinetic-rigid syndrome that was poorly responsive to L-dopa, autonomic failure, and cerebellar ataxia. PET findings for the 10 MSA patients were compared with those for 13 age-matched controls, 8 subjects with L-dopa responsive Parkinson's disease (PD), and 7 subjects with pure autonomic failure (PAF). Influx constants, Ki, reflecting specific 18F-dopa uptake into striatal tissue, were severely reduced in the putamen and caudate of the 10 MSA subjects (mean putamen Ki 0.005 min-1 MSA vs 0.013 min-1 controls; mean caudate Ki 0.007 min-1 MSA vs 0.013 min-1 controls). Reduction of putamen, but not caudate, 18F-dopa uptake correlated with severity and duration of locomotor disability. Eight patients with PD, and a similar degree and duration of locomotor disability to the patients with MSA, demonstrated equal impairment of mean putamen 18F-dopa uptake, but significant preservation of mean caudate function. The 7 PAF patients had normal mean levels of putamen and caudate 18F-dopa uptake, although 1 individual PAF patient had significantly impaired striatal function. The MSA and PD groups of subjects both showed significantly reduced levels of specific striatal S-11C-NMF binding, again caudate function being relatively preserved in PD. It is concluded that in both MSA and PD there is a parallel decline of striatal dopamine storage capacity and reuptake site integrity, probably reflecting a loss of nigrostriatal nerve terminals. Caudate function is relatively preserved in PD compared with MSA. The majority of PAF patients have an intact nigrostriatal dopaminergic system, suggesting that PAF is a condition distinct from PD and MSA in spite of some pathological similarities. PET is capable of detecting subclinical nigrostriatal involvement in PAF patients when this is present.

Adult↗
PubMed1990

Cortical outflow to proximal arm muscles in man.

Corticospinal influences on two antagonistic muscles of the shoulder were studied in 6 normal volunteers. Recordings were made of the discharges of single motor units from the deltoid and pectoralis major muscles and poststimulus time histograms constructed following either anodal electrical or magnetic cortical stimulation via the scalp. Contralateral anodal stimulation caused narrow short-latency peaks of excitation in motor units from both muscles, probably indicative of the arrival of the D or direct corticospinal volley. The size of the peaks led to estimates of the underlying excitatory postsynaptic potentials (EPSP) amplitude of 5.5 mV for the deltoid and 2.2 mV for the pectoralis motor units. Magnetic stimulation over the vertex caused multiple early peaks of excitation in motor units from both muscles but these peaks began at a greater latency than those produced by anodal stimulation. Additionally, magnetic cortical stimulation (and, occasionally, contralateral anodal stimulation) caused a previously undescribed period of medium latency excitation in both muscles. These medium latency periods of excitation differed from the earlier events in that they occurred independently of the direction of current flow in the magnetic coil. This raises the possibility that they are the consequence of stimulation of bilaterally distributed cortical motor outflow pathways. The short-latency excitation strongly suggests that, in man, corticomotoneuronal projections exist to proximal as well as distal muscles of the contralateral arm. The strength of the projection to deltoid assessed by this method is similar to that to an intrinsic muscle of the hand and significantly larger than that to its antagonist, pectoralis. The possible bilateral organization of the additional medium-latency projection to these proximal arm muscles may contribute to two characteristic clinical features after a unilateral cerebral lesion, such as stroke: the relative sparing of proximal arm strength compared with distal and, secondly, ipsilateral weakness.

Adult↗
PubMed1990

Mitochondrial complex I deficiency in Parkinson's disease.

The structure and function of mitochondrial respiratory-chain enzyme proteins were studied postmortem in the substantia nigra of nine patients with Parkinson's disease and nine matched controls. Total protein and mitochondrial mass were similar in the two groups. NADH-ubiquinone reductase (Complex I) and NADH cytochrome c reductase activities were significantly reduced, whereas succinate cytochrome c reductase activity was normal. These results indicated a specific defect of Complex I activity in the substantia nigra of patients with Parkinson's disease. This biochemical defect is the same as that produced in animal models of parkinsonism by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and adds further support to the proposition that Parkinson's disease may be due to an environmental toxin with action(s) similar to those of MPTP.

Electron Transport Complex II↗
PubMed1990

Anatomic and disease specificity of NADH CoQ1 reductase (complex I) deficiency in Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is thought to produce parkinsonism in humans and other primates through its inhibition of complex I. The recent discovery of mitochondrial complex I deficiency in the substantia nigra of patients with Parkinson's disease has provided a remarkable link between the idiopathic disease and the action of the neurotoxin MPTP. This article shows that complex I deficiency in Parkinson's disease is anatomically specific for the substantia nigra, and is not present in another neurodegenerative disorder involving the substantia nigra. Evidence is also provided to show that there is no correlation between L-3,4-dihydroxyphenylalanine therapy and complex I deficiency. These results suggest that complex I deficiency may be the underlying cause of dopaminergic cell death in Parkinson's disease.

Citrate (si)-Synthase↗
PubMed1990

Decreased ferritin levels in brain in Parkinson's disease.

Ferritin levels were measured in postmortem brain tissue from patients dying with Parkinson's disease [treated with L-3,4-dihydroxyphenylalanine (L-DOPA)] and from control patients. Ferritin levels were decreased in the substantia nigra, caudate-putamen, globus pallidus, cerebral cortex, and cerebellum when compared with age-matched control tissues. However, in CSF from L-DOPA-treated patients and in serum from L-DOPA-treated and untreated parkinsonian patients, ferritin levels were normal. Previous studies have suggested an increased total iron content in substantia nigra of parkinsonian brain. The failure of substantia nigra ferritin formation to be stimulated by increased iron levels suggests some defect in iron handling in this critical brain region in Parkinson's disease. The reason for decreased ferritin levels throughout the parkinsonian brain is not clear but does not seem to reflect a general system deficit in ferritin.

Brain Chemistry↗