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C D Marsden

Publications and source records attributed to C D Marsden.

At least 181 records · Page 10Linked to original sources
PubMed1995

Effect of 7-nitro indazole on quinolinic acid-induced striatal toxicity in the rat.

Nitric oxide (NO) is implicated as a mediator of cell death in models of neurodegenerative disease. However, the precise role of NO in neuronal degeneration remains controversial. In the present study we employed 7-nitro indazole (7-NI), reportedly a selective inhibitor of neuronal nitric oxide synthase (nNOS) in vivo, to investigate the possible involvement of NO in quinolinic acid (QA)-induced striatal toxicity in the rat. Intrastriatal injection of QA (30 nmol) caused loss of NADPH diaphorase (48%), NOS (48%) and acetylcholinesterase (AChE; 22%) positive neurones and a loss of NOS activity (78%) in striatal homogenates. 7-NI (30 mg kg-1, i.p. every 4 h for 20 h) did not affect the loss of NADPH diaphorase (52%), NOS (52%) and AChE (16%) positive neurones or the loss of NOS activity (66%) in striatal homogenates. The present study does not support a role for NO in QA-induced striatal toxicity.

Acetylcholinesterase↗
PubMed1995

Pain and remote weakness in limbs injected with botulinum toxin A for writer's cramp.

We describe two cases of a syndrome resembling neuralgic amyotrophy that occurred in limbs injected with botulinum toxin for writer's cramp. In both cases, one of the injections was followed by pain and the next, 7-10 weeks later, by weakness. We believe that unexplained pain in the shoulder region after an injection of botulinum toxin contraindicates a second injection.

Adult↗
PubMed1995

Inhibition of alpha-ketoglutarate dehydrogenase by isoquinoline derivatives structurally related to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

Defects in complex I and alpha-ketoglutarate dehydrogenase (alpha-KGDH) occur in the substantia nigra in Parkinson's disease (PD). Isoquinoline derivatives structurally related to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 1-methyl-4-phenylpyridinium (MPP+) are implicated in the cause of PD as endogenous toxins and are inhibitors of complex I. However, their effects on alpha-KGDH and other mitochondrial non-respiratory chain enzymes are unknown. We have examined the effects of six isoquinoline derivatives (isoquinoline, N-methylisoquinolinium, N-n-propylisoquinolinium, 1,2,3,4-tetrahydroisoquinoline, N-methyl-1,2,3,4-tetrahydroisoquinoline and salsolinol) and MPP+ on the activities of alpha-KGDH, citrate synthase (CS) and glutamate dehydrogenase (GDH) in mitochondrial fragments from rat forebrain. None of the compounds examined had any effect on CS or GDH activity. In contrast, all isoquinoline derivatives investigated and MPP+ inhibited alpha-KGDH activity in a concentration-dependent manner with IC50s ranging from 2.0 to 18.9 mM. MPP+ was previously shown to inhibit alpha-KGDH, but this is the first report of inhibition of alpha-KGDH by isoquinoline derivatives. These findings may represent an additional mechanism contributing to mitochondrial dysfunction and cell death in Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1995

Stimulation of adenylate cyclase activity by benzazepine D-1 dopamine agonists with varying efficacies in the 6-hydroxydopamine lesioned rat--relationship to circling behaviour.

The ability of benzazepine D-1 dopamine agonists with varying efficacies in stimulating adenylate cyclase and to induce contralateral circling was investigated in rats with unilateral 6-hydroxydopamine lesions of the medial forebrain bundle. In the 6-hydroxydopamine lesioned rats, the benzazepines SKF 38393 (7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine), SKF 75670 (3-CH3 analogue), SKF 80723 (6-Br analogue), SKF 83959 (6-Cl, 3-CH3, 3'-CH3 analogue), SKF 83565 (6-Cl, 3-CH3, 3'-Cl analogue) and SKF 82958 (6-Cl, 3-C3H5 analogue), all produced contralateral circling. The rank order of efficacies (maximal effect, Emax) being, SKF 83565 = SKF 75670 = SKF 83959 = SKF 80723 > SKF 38393 >> SKF 82958. In striatal slices from the intact hemisphere, dopamine, SKF 82958, SKF 80723 and SKF 75670 stimulated adenylate cyclase activity. The rank order of efficacies being SKF 82958 (109%) = dopamine (100%) = SKF 80723 (98%) > SKF 75670 (72%). Although, SKF 38393 (67%), SKF 83565 (64%) and SKF 83959 (59%) tended to stimulate adenylate cyclase activity, this effect did not reach statistical significance. In the 6-hydroxydopamine lesioned hemisphere, basal levels of adenylate cyclase activity were lower (-25%) than in the intact hemisphere. The maximal stimulation of adenylate cyclase activity (expressed as % basal levels) produced by dopamine and the benzazepines in the denervated striatum was greater than observed in the intact striatum. The rank order of efficacies in the dopamine denervated striatum being SKF 82958 (124%) > SKF 80723 (109%) = dopamine (100%) > SKF 38393 (82%) = SKF 83959 (77%) = SKF 83565 (70%) > SKF 75670 (55%). Moreover, dopamine stimulated adenylate cyclase activity in the denervated striatum with greater potency than in the intact side. The ability of the benzazepine derivatives to induce circling in the 6-hydroxydopamine lesioned rat is consistent with the general increase in the efficacies of dopamine and benzazepine stimulated adenylate cyclase activity in the dopamine denervated striatum. However, the maximal effects for inducing circling and stimulating adenylate cyclase activity do not correspond (e.g. SKF 82958 and SKF 75670). This discrepancy may reflect the involvement of other factors including a behavioural role for extrastriatal D-1 dopamine receptors and/or transduction systems other than adenylate cyclase.

Adenylyl Cyclases↗
PubMed1995

Short- and long-term changes in striatal and extrastriatal dopamine uptake sites in the MPTP-treated common marmoset.

The 'short-term' (15-30 days) and 'long-term' (18-42 months) effects of the systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on [3H]mazindol binding to dopamine uptake sites was investigated in the common marmoset. In the 'short-term' MPTP-treated group, [3H]mazindol binding was reduced in the caudate-putamen (by -82 to -98% with respect to controls), substantia nigra pars compacta (-71 to -84%), ventral tegmental area (-72%) and nucleus accumbens (-54%). [3H]Mazindol binding in the globus pallidus, frontal cortex and substantia nigra pars reticulata was much lower and was unaffected by MPTP treatment. In the 'long-term' MPTP-treated group [3H]mazindol binding was still greatly reduced in the substantia nigra pars compacta (by -76 to -89%), ventral tegmental area (-71%) and most of the caudate-putamen (-69 to -98%), although the reduction in [3H]mazindol binding in the nucleus accumbens (-27%) and rostroventral caudate nucleus (-69%) was less than in the 'short-term' MPTP-treated group. The motor deficits induced by MPTP treatment in the common marmoset are largely reversible with increasing survival times (Ueki et al., 1989, Neuropharmacology 28, 1089). In the present study, the apparent 'recovery' in [3H]mazindol binding in the rostroventral caudate nucleus and nucleus accumbens may indicate regeneration of dopamine neurone terminals in these regions and this may contribute to the behavioural recovery seen in this primate model of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1995

Differentiation of multiple system atrophy from idiopathic Parkinson's disease using proton magnetic resonance spectroscopy.

Proton magnetic resonance spectroscopy, localized to the lentiform nucleus, was carried out in 7 patients with the pure or predominantly striatonigral variant (SND) of multiple system atrophy (MSA), 5 patients with the olivopontocerebellar variant of MSA, 9 patients with a clinical diagnosis of idiopathic Parkinson's disease (IPD), and 9 healthy age-matched controls. The MSA group with predominantly striatonigral involvement showed a significant reduction in the N-acetylaspartate (NAA)/creatine ratio (median, 1.19; range, 0.96-2.0; p < 0.02) compared with the NAA/creatine ratio from the control group (median, 1.76; range, 1.61-2.0). In contrast, the IPD group had a normal NAA/creatine ratio (median, 1.82; range, 1.19-2.31; p > 0.05). The NAA/creatine ratio was markedly reduced in 6 of the SND patients and in only 1 IPD patient. The choline/creatine ratio was also significantly lower in the SND group (median, 1.02; range, 0.91-1.23; p < 0.04) compared with the control group (median, 1.22; range, 1.05-1.65). The IPD group showed a normal lentiform choline/creatine ratio (median, 1.13; range, 0.89-1.65; p = 0.25) compared with controls. The olivopontocerebellar group also showed a significant reduction in the NAA/creatine ratio from the lentiform nucleus (median, 1.47; range, 1.22-1.68; p < 0.01) compared with the controls as well as a nonsignificant reduction in the choline/creatine ratio (median, 0.93; range, 0.85-1.27; p < 0.4).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Overactive prefrontal and underactive motor cortical areas in idiopathic dystonia.

Regional cerebral blood flow was measured using H2(15)O and positron emission tomography in a group of 6 patients with idiopathic torsion dystonia and in a group of 6 control subjects. Subjects were scanned while at rest and when performing paced joystick movements in freely chosen directions with the right hand. Patients with idiopathic torsion dystonia showed significant overactivity in the contralateral lateral premotor cortex, rostral supplementary motor area, Brodmann area 8, anterior cingulate area 32, ipsilateral dorsolateral prefrontal cortex, and bilateral lentiform nucleus. Significant underactivity was found in the caudal supplementary motor area, bilateral sensorimotor cortex, posterior cingulate, and mesial parietal cortex. These results are consistent with inappropriate overactivity of striatofrontal projections and impaired activity of motor executive areas in idiopathic torsion dystonia and may explain the simultaneous dystonic posturing and bradykinesia evident in these patients.

Adult↗
PubMed1995

Positron emission tomography studies on the dopaminergic system and striatal opioid binding in the olivopontocerebellar atrophy variant of multiple system atrophy.

Ten patients with sporadic olivopontocerebellar atrophy and autonomic failure were studied with positron emission tomography. Subjects underwent both an [11C]diprenorphine and an [18F]fluorodopa scan. The mean caudate-occipital uptake ratio for [11C]diprenorphine was significantly reduced to 88% and the putamen-occipital uptake ratio to 85% of the control values. Individually, 4 of the 10 patients had significantly reduced opioid binding in the putamen. Mean putamen [18F]fluorodopa uptake was significantly diminished (to 71% of the control mean); individually 7 patients had significantly reduced uptake. There was a significant positive correlation between putamen-occipital uptake ratios for [11C]diprenorphine and putamen uptake of [18F]fluorodopa. Our results suggest that subclinical nigrostriatal dysfunction is present in the majority of patients with sporadic olivopontocerebellar atrophy, in accordance with it being part of the spectrum of multiple system atrophy.

Autonomic Nervous System Diseases↗
PubMed1995

Motor reorganization in acquired hemidystonia.

Regional cerebral blood flow (rCBF) was measured with H2(15)O positron emission tomography in 5 patients with acquired hemidystonia (AHD) due to structural lesions of the basal ganglia or posterior thalamus contralateral to the dystonic limb. Patients were scanned at rest and when performing paced joystick movements in freely chosen directions with the dystonic and then the unaffected arm. Findings were compared with those of 5 age-matched controls performing joystick movements with the right arm. At rest, there was decreased activity in ventroanterior thalamus, posterior thalamus, angular gyrus ipsilateral to the lesion, and bilateral frontoorbital cortex. At a similar level of significance, increased resting activity was found in lentiform nucleus, hippocampus, and anterior insula contralateral to the lesion. Using the affected arm, AHD cases showed significant overactivity of contralateral prefrontal, lateral premotor cortex, rostral supplementary motor area, anterior cingulate area 32, bilateral sensorimotor cortex (SMC) and insula, mesial parietal cortex, and ipsilateral cerebellum. There was similar frontal overactivity when the unaffected arm performed the joystick movements, though SMC and insula overactivity was contralateral rather than bilateral. The associated frontal overactivity on movement is consistent with acquired dystonia being a syndrome of thalamofrontal disinhibition due to structural disruption of basal ganglia inhibitory control. Our findings also suggest that cortical activation during movement of the unaffected limb is abnormal in acquired hemidystonia.

Adult↗
PubMed1995

Movement-related cortical potentials preceding repetitive and random-choice hand movements in Parkinson's disease.

The movement-related cortical electroencephalographic potential was recorded from scalp electrodes in 8 patients with idiopathic Parkinson's disease studied at least 12 hours after withdrawal of their normal drug therapy, and compared with the results from a group of 8 age-matched control subjects. Two types of self-paced voluntary arm movements were examined: repetitive forward movement of a joystick, and random-choice movements of the same joystick in which subjects had to choose freely the direction in which they were to move the stick (forward, backward, left, or right). In normal subjects, the movement-related cortical potential was larger prior to random-choice movements, whereas in the patients, the amplitude was the same in both tasks. The implication is that processes involved in self-selection of movement are abnormal in Parkinson's disease. This may contribute to the difficulty that patients have in initiating voluntary movement in the absence of any external cues.

Adult↗
PubMed1995

The bereitschaftspotential preceding stepping in patients with isolated gait ignition failure.

The cerebral activity preceding voluntary, self-paced ankle dorsiflexion movements while seated was compared with that before a stepping movement of the same foot while standing in four patients with isolated gait ignition failure. Results within the patients group were variable, but all exhibited some increase in the Bereitschaftspotential (BP) amplitude when stepping as compared with sitting, similar to that seen in normal subjects. This differs from previous results in patients with Parkinson's disease in which stepping was not accompanied by a normal increase in BP amplitude. This difference suggests that the mechanisms responsible for the start hesitation that is common to both Parkinson's disease and gait ignition failure may differ in the two conditions.

Aged↗
PubMed1995

Patterns of regional cerebral blood flow in corticobasal degeneration studied using HMPAO SPECT; comparison with Parkinson's disease and normal controls.

Corticobasal degeneration (CBD) is a rare syndrome characterised by an asymmetrical rigidity with localised cortical signs, particularly apraxia. Using positron emission tomography, abnormal patterns of cortical metabolism have recently been shown. We have studied patterns of regional cerebral blood flow (rCBF) using single photon emission tomography, with the tracer 99Technetium hexamethylpropylenamine (HMPAO), in subjects with CBD. In subjects with CBD, compared with 12 age-matched normal controls, in the clinically more affected hemisphere a characteristic pattern was found with significant reductions in HMPAO uptake in the posterior frontal cortex (by 11.5%), and in the superior, inferior, anterior, and posterior parietal cortex (by 12.2, 12.9, 12.9, and 9.7, respectively). Reduced uptake was also found in the caudate (9.3%), putamen (9.7%), and thalamus (8.6%). In contrast, HMPAO uptake in the temporal and occipital cortex was normal. In comparison with 12 Parkinson's disease (PD) controls, significant reduced uptake was seen in the thalamus (9.0%), posterior frontal (8.9%), and inferior (9.9%), and anterior parietal (9.5%) cortex. A similar pattern of impaired uptake was seen in the clinically less/unaffected cerebral hemisphere in patients with CBD compared with normal controls, with a significant reduction in HMPAO uptake in the thalamus (6.8%), superior parietal (9.6%) and anterior parietal (7.6%), and posterior parietal (7.3%) cortex. This implies that the disease process is bilateral even in those cases with clinically unilateral disease. This widely available technique may be useful in the early diagnosis of CBD and in differentiation from other extrapyramidal disorders.

Age Factors↗
PubMed1995

Teaching tape for the motor section of the unified Parkinson's disease rating scale.

We developed a teaching tape of the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS) to provide investigators with a visual document of three raters' interpretations of the scoring system for each item except rigidity. The rate of agreement for the selected samples was always significant, with Kendall's coefficient of concordance W ranging between 0.97 and 0.62. We also provided full UPDRS ratings on sample patients that may be used for training and for multicenter studies to assure uniformity of rating. The study identified several items of the UPDRS motor examination for which written instructions were vague, including speech, action tremor, finger taps, rapid alternating movements, and postural stability. Future versions of the scale should address these problems and correct ambiguities. This project offers the first attempt to provide a visual analog for the UPDRS.

Audiovisual Aids↗
PubMed1995

L-dihydroxyphenylalanine and complex I deficiency in Parkinson's disease brain.

There is evidence for a 37% deficiency of complex I activity in Parkinson's disease (PD), which appears to be specific for PD amongst parkinsonian syndromes and selective for the substantia nigra within the central nervous system. Rat studies have shown that, in the context of a normal nigrostriatal dopaminergic cell population, L-dihydroxyphenylalanine (L-dopa) causes a reversible 25% defect of complex I activity in nigral and striatal tissue. Analysis of striatal tissue from PD patients after prolonged exposure to high-dose L-dopa does not show such a defect. Results of these and other studies suggest that L-dopa therapy does not cause complex I deficiency in PD striatum. However, it cannot be excluded that, in the particular environment of the PD substantia nigra, L-dopa may enhance a preexisting complex I defect.

Aged↗
PubMed1995

Movement disorders in multiple sclerosis.

Movement disorders (MD), other than tremor, associated with multiple sclerosis (MS) occur infrequently. We report 14 new cases of whom nine had dystonia, three parkinsonism, and two had myoclonus. We also reviewed 135 such cases from the literature. From an analysis of the individual MDs and the site of the lesions described, we conclude that paroxysmal dystonias (tonic spasms), ballism/chorea, and palatal myoclonus can be caused by demyelinating lesions. Parkinsonism, dystonia, and other types of myoclonus, however, often appear to be coincidental.

Adolescent↗
PubMed1995

The movement-related cortical potential is abnormal in patients with idiopathic torsion dystonia.

Voluntary movements, such as the self-paced finger extension task used in the present experiments, are preceded by a slowly rising negative electroencephalographic potential [the movement-related cortical potential (MRCP)]. The early NS1 component of the potential was no different in patients with primary dystonia affecting the arm (n = 6) compared with matched controls. In contrast, the peak amplitude of the MRCP was smaller in the patients, despite the fact that the movements made by the two groups were very similar; it was of equal size over both left and right hemispheres, rather than being larger on the side contralateral to the movement. These results are similar to those observed by others in patients with symptomatic dystonia secondary to lesions of the basal ganglia or their output pathways and may reflect abnormal basal ganglia input to motor areas of cortex before the onset of a self-paced movement.

Adult↗
PubMed1995

Chronic L-DOPA administration induces dyskinesias in the 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine-treated common marmoset (Callithrix Jacchus).

Dyskinesias occur in the majority of patients with Parkinson's disease chronically treated with L-DOPA and also occur in several nonhuman primate species after 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine (MPTP) and L-DOPA treatment. The common marmoset (Callithrix jacchus) shows parkinsonian motor deficits after MPTP administration, and we now report dyskinesias occurring in this species during chronic L-DOPA exposure. Marmosets rendered chronically parkinsonian after MPTP administration were treated orally with L-DOPA plus carbidopa for 3 weeks. After several days the animals began to display chorea, choreoathetosis, and dystonia. The severity of dyskinesias varied between the animals, with the most severely parkinsonian animals displaying the most dyskinetic movements. Each animal showed an idiosyncratic pattern of dyskinesias, which was highly reproducible. These L-DOPA-primed animals also received other D2 D1, and mixed D1/D2 agonist drugs. Quinpirole, bromocriptine, pergolide, apomorphine, and A-77636 all produce dyskinesias that were identical in character to those seen after L-DOPA administration, but the D1 agonist A-77636 gradually abolished dyskinesias while preserving its antiparkinsonian activity. The MPTP-treated marmoset provides a useful model in which to study dyskinesias in Parkinson's disease and to examine new therapeutic strategies aimed at alleviating this common side effect of chronic dopamine replacement therapy.

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