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C D Marsden

Publications and source records attributed to C D Marsden.

At least 361 records · Page 20Linked to original sources
PubMed1992

New insights into the cause of Parkinson's disease.

Current concepts as to the cause of Parkinson's disease (PD) suggest an inherited predisposition to environmental or endogenous toxic agents. Study of the substantia nigra after death in PD has highlighted three major changes: (1) evidence of oxidative stress and depletion of reduced glutathione; (2) high levels of total iron, with reduced ferritin buffering; and (3) mitochondrial complex I deficiency. Which of these is the primary event, generating a secondary cascade of changes culminating in nigral cell death, is unknown. In presymptomatic Lewy body-positive control brains, the nigra shows depletion of reduced glutathione content and, possibly, a reduction of complex I activity. Whatever the significance of these various abnormalities, be they causal or secondary, they provide novel targets for the development of new strategies to treat the cause of PD.

Aging↗
PubMed1992

Essential tremor.

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Data Collection↗
PubMed1992

Isolated tremor and disruption of the nigrostriatal dopaminergic system: an 18F-dopa PET study.

We measured striatal 18F-dopa influx constants (Ki) for 20 patients with isolated, predominantly postural, tremor (eight familial, 12 sporadic) and 11 with predominantly rest tremor. Results were compared with 30 controls and 16 Parkinson's disease (PD) patients. The eight familial essential tremor (ET) patients had normal striatal 18F-dopa uptake. Two of the 12 sporadic postural tremor patients had subnormal putamen 18F-dopa Ki, one (who later became akinetic) falling in the PD range. The mean putamen 18F-dopa uptake of the 11 rest tremor patients was reduced to PD levels (51% of normal). Our findings argue against an association between ET and PD, but support the existence of a "benign" tremulous variant of PD. The presence of low-amplitude rest tremor, cogwheel rigidity, reduced arm swing, and short tremor duration was not a useful predictor of nigral dysfunction in patients with postural tremor. In contrast, patients with predominantly rest tremor, particularly with onset in the leg, consistently showed reduced putamen 18F-dopa uptake.

Adult↗
PubMed1992

Botulinum toxin treatment of spasmodic torticollis.

We reviewed the efficacy and adverse effects of repeated botulinum toxin injections into hyperactive neck muscles of 107 successive patients with spasmodic torticollis. They received 510 injection treatments over a median period of 15 months (range 3-42 months). One patient failed to benefit at all, but 101 (95%) patients reported considerable (moderate or excellent) benefit from at least one treatment. On a global subjective response rating, 93% of 429 treatments resulted in some improvement and 76% in moderate or excellent improvement. Pain reduction followed 89% of 190 treatments with moderate or excellent reduction after 66%. Median duration of benefit was 9 weeks. All torticollis types responded equally well and injections into two (or more) involved neck muscles were more effective than injection into a single muscle. The most frequent adverse effect was dysphagia, occurring after 44% of all treatments, but this was severe after only 2%. Antibodies to botulinum toxin were detected in the serum of three out of the five patients in whom loss of treatment efficacy occurred. We conclude that botulinum toxin treatment is the most effective available therapy for spasmodic torticollis and practical advice is provided for anyone wishing to set up the technique.

Adult↗
PubMed1991

Effects of 6-hydroxydopamine lesions of the nigrostriatal pathway on striatal serotonin innervation in adult rats.

The effects of 6-hydroxydopamine lesions of the nigrostriatal pathway on striatal serotonin (5-HT) innervation have been examined using immunohistochemistry in adult rats. One day after lesioning, a large number of swollen and densely stained 5-HT-immunoreactive fibers appeared around the lesion which was almost completely void of 5-HT-immunoreactivity. Four weeks after lesioning, a significant reduction in 5-HT innervation density was verified in the ventral portion of the rostral neostriatum and in the caudal neostriatum of the lesioned side. Eight weeks after lesioning, a similar decrease in 5-HT innervation density was observed in the neostriatum on the lesioned side. Some aberrant 5-HT-immunoreactive fibers were found around the lesion of the nigrostriatal pathway. These results indicate that 6-hydroxydopamine lesions of the nigrostriatal bundle of adult rats induce a reduction in striatal serotonin innervation density as well as aberrant morphology of 5-HT-immunoreactive fibers around the lesion.

Animals↗
PubMed1991

A redox reaction between MPP+ and MPDP+ to produce superoxide radicals does not impair mitochondrial function.

Rat brain mitochondria were incubated with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its two metabolites (1-methyl-4-phenyl-2,3-dihydropyridium (MPDP+) and 1-methyl-4-phenylpyridinium (MPP+), and O2 uptake was assessed. MPP+ (500 and 1000 microM) inhibited state 3 and state 4 respiration with a reduction in the respiratory control ratio (RCR). In the presence of MPTP or MPDP+ (100-1000 microM) no inhibition of mitochondrial function occurred. Incubation with MPP+ (100-1000 microM) in combination with equimolar concentrations of MPDP+ or MPTP (100-1000 microM) did not increase the inhibition of mitochondrial function produced by MPP+ alone. Inhibition of mitochondrial function produced by MPP+ (500 microM) was not reduced by incorporation of superoxide dismutase (SOD) (50-1000 units/mL). However, the RCR in the presence of 500 microM MPP+ and 1000 units/mL SOD was not different from control values. SOD did not prevent the inhibition of state 3 and state 4 respiration produced by the combination of MPP+ and MPDP+. The results suggest that a redox reaction between MPP+ and MPDP+ to generate superoxide radicals does not contribute to the impairment of mitochondrial function produced by MPTP administration.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1991

Serotonergic sprouting in the neostriatum after intrastriatal transplantation of fetal ventral mesencephalon.

The sprouting of serotonergic fibers into the neostriatum of 6-OHDA-lesioned rats should be considered, when assessing the functional aspects of ventral mesencephalic grafts. The degree of serotonergic fiber growth into the neostriatum of rats subjected to unilateral 6-OHDA lesions followed by fetal ventral mesencephalic grafts was examined immunohistochemically. As a measure of serotonergic innervation density, the total length of immunoreactive fibers was quantified as percent area. Four weeks after transplantation, there was complete recovery of (+)-amphetamine-induced rotation. All of the ventral mesencephalic grafts contained serotonin-immunoreactive cells, but much fewer in number than the tyrosine hydroxylase-positive cells found in the same grafts. However, there was significant serotonergic hyperinnervation throughout the transplanted neostriatum compared with the control side. The hyperinnervation derived from the grafted neurons was most marked in the dorsal and lateral sectors of the rostral neostriatum. At 24 weeks after transplantation, the implanted neostriatum still showed a dense serotonergic innervation.

Amphetamine↗
PubMed1991

Acute effects of D-1 and D-2 dopamine receptor agonist and antagonist drugs on basal ganglia [Met5]- and [Leu5]-enkephalin and neurotensin content in the rat.

The effects of acute systemic injection of the D-1 agonist SKF 38393 (2.5-20 mg/kg) or the D-1 antagonist SCH 23390 (0.25-2.0 mg/kg), and of the D-2 agonist quinpirole (0.12-1.0 mg/kg) or the D-2 antagonist sulpiride (25-100 mg/kg) on the neuropeptide content of rat basal ganglia were investigated. In striatum, the [Met5]- and [Leu5]-enkephalin content was unaffected by administration of SKF 38393 or SCH 23390. Quinpirole had no effect on [Met5]- and [Leu5]-enkephalin levels but sulpiride produced an increase in both [Met5]- and [Leu5]-enkephalin content. In the nucleus accumbens, SKF 38393 decreased and SCH 23390 increased [Met5]- and [Leu5]enkephalin levels. Quinpirole decreased [Met5]- and [Leu5]-enkephalin levels, while sulpiride decreased [Leu5]-enkephalin levels alone. The content of [Leu5]- but not [Met5]-enkephalin levels in the substantia nigra was increased by administration of SKF 38393, and decreased by SCH 23390. Quinpirole and sulpiride were without effect on the [Met5]- or [Leu5]-enkephalin content of substantia nigra. Neurotensin levels in striatum were increased by administration of SKF 38393 and decreased by SCH 23390. Similarly, quinpirole decreased the neurotensin content while sulpiride caused an increase. In the nucleus accumbens, the neurotensin content was not affected by administration of SKF 38393 but increased by SCH 23390. Neither quinpirole nor sulpiride altered neurotensin levels in the nucleus accumbens. Neurotensin levels in substantia nigra were unaffected by the administration of SKF 38393 and SCH 23390, or by quinpirole and sulpiride. These results indicate that acute administration of D-1 and D-2 agonist and antagonist drugs can alter the levels of [Met5]- and [Leu5]-enkephalin and neurotensin in basal ganglia. However, there are marked differences between brain regions in the regulation of peptide levels by acute D-1 and D-2 receptor occupation.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

The effect of sleep on the dyskinetic movements of Parkinson's disease, Gilles de la Tourette syndrome, Huntington's disease, and torsion dystonia.

The effect of sleep on the involuntary movements or dyskinesias in Parkinson's disease, Huntington's disease, primary and secondary torsion dystonia, and Gilles de la Tourette syndrome was studied in a total of 52 patients and 10 normal subjects using video electroencephalographic telemetry. Movements typical of the wake pattern were seen occasionally during unequivocal sleep in all but two completed studies, and in each condition reappeared under similar circumstances. The movements were most likely to occur after awakenings or lightenings of sleep, or in stage one sleep. The movements were very rare during the deeper phases of sleep. Those movements that occurred during sleep without awakenings were usually preceded by arousal phenomena and, rarely, by sleep spindles or slow waves. The control group showed normal "semipurposeful" movements under the same conditions during sleep. The rare appearance of the different dyskinesias and normal movements under similar circumstances during sleep could be a result of common effects on the generator systems or changes in the excitability of the final common motor pathway.

Brain↗
PubMed1991

Correlation of phasic muscle strength and corticomotoneuron conduction time in multiple sclerosis.

Central motor conduction times for the adductor pollicis muscle, the twitch force of that muscle to scalp magnetic motor cortex stimulation, and the maximum force of phasic voluntary contraction of the same muscle were measured in 15 patients with multiple sclerosis. Two tests of manual dexterity of the same hand also were studied: the Purdue pegboard test, and the maximal frequency of a scissors movement of the thumb and index finger. The patients had normal strength or minimal weakness of the intrinsic muscles of the hand on clinical examination. The mean central motor conduction times for the adductor pollicis muscle for the patients were longer than normal, the peak twitch force of the adductor pollicis muscle evoked by cortical stimulation and the maximum force of a phasic voluntary contraction of the adductor pollicis muscle were smaller than normal. There were strong correlations between all these measures. Central motor conduction time in the patients was inversely correlated with voluntary phasic force and the twitch force after cortical stimulation. That is, the longer the central motor conduction time, the weaker the force. Prolonged central motor conduction time is likely to be accompanied by conduction block in corticomotoneuron pathways. The correlation of central motor conduction time with voluntary phasic force and the twitch force most likely reflects the degree of conduction block and temporal dispersion rather than delay in conduction per se. These results indicate that objective assessments of phasic muscle strength may reveal correlations with central motor conduction time that are not evident on conventional clinical examination which assesses tonic muscle contraction strength.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

A genetic study of idiopathic focal dystonias.

A genetic study of idiopathic focal dystonias was undertaken by examining 153 first-degree relatives of 40 index patients with torticollis (14 patients), other focal cranial dystonias (16 patients), and writer's cramp (10 patients). Nine relatives with dystonia were identified in 6 families; 8 of these had symptoms such as clumsiness or tremor, but none were aware of any dystonia. A further 4 relatives, now decreased, were affected by history. Overall, 25% of index patients had relatives with dystonia. The results of segregation analysis suggested the presence of an autosomal dominant gene or genes with reduced penetrance as a common cause for focal dystonia. Segregation ratios were not significantly different from those ratios observed in generalized or segmental dystonia in the United Kingdom, and it is possible that a single autosomal dominant gene mutation is responsible for inherited dystonia in the majority of patients irrespective of distribution or severity.

Adult↗
PubMed1991

Percutaneous electrical stimulation of corticospinal pathways at the level of the pyramidal decussation in humans.

Stimulation over the base of the skull can activate descending motor pathways to produce electromyographic (EMG) responses in muscles of the arm and leg. The evoked EMG responses were larger when the muscles were preactivated by a small voluntary contraction compared to when they were completely relaxed. The latency of these responses in preactivated muscles was approximately midway between that produced by electrical stimulation over the motor cortex, and by electrical stimulation over the cervical enlargements. With horizontally spaced electrodes, the latency difference between cortical and brainstem stimulation was 1.8 milliseconds in all muscles tested. The latency difference between cervical and brainstem stimulation was 3.9 milliseconds for the first dorsal interosseous and 2.6 milliseconds for tibialis anterior muscles. These values suggest that brainstem stimulation occurs at the level of the cervicomedullary junction. With vertically spaced electrodes in the midline, stimulation often occurs at a higher level. The EMG responses from brainstem stimulation differed from those following cortical stimulation in two ways: (1) They were simpler in form, and (2) their onset latency was the same in active as it was in relaxed muscles. This suggests that brainstem stimulation evoked a large descending motor volley in comparison with the multiple volleys that cortical stimulation can produce. Collision experiments between cortical and brainstem volleys indicated that the major part of the responses evoked by brainstem stimulation were conducted via the large-diameter component of the corticospinal tract.

Action Potentials↗
PubMed1991

Dopa-responsive dystonia: [18F]dopa positron emission tomography.

The syndrome of dopa-responsive dystonia comprises a minority of patients with dystonia, yet it is of considerable diagnostic importance because patients respond dramatically to L-dopa therapy. Benefits from this treatment are lasting, and the problems associated with long-term L-dopa therapy in patients with Parkinson's disease are generally absent. It has been suggested that this condition is due to a defect in the dopamine synthetic pathway, which is bypassed when patients are treated with L-dopa. We have studied [18F]dopa uptake in 6 patients with classic dopa-responsive dystonia (5 familial patients and 1 sporadic patient), aged 18 to 66 years. Data have been analyzed according to a graphic approach, calculating an influx constant for each region studied. We have also studied a seventh, clinically atypical, patient with juvenile dystonia-parkinsonism. Similar data have been calculated for a group of 10 healthy control subjects and 10 patients with Parkinson's disease. The 6 patients with typical dopa-responsive dystonia had a modest but significant reduction in the uptake of tracer into both caudate and putamen, which indicates a defect in the decarboxylation, vesicular uptake, and storage of [18F]dopa. This argues against the proposition that dopa-responsive dystonia is due to an inherited defect of tyrosine hydroxylase alone. In the atypical patient, however, we found a greater reduction of [18F]dopa uptake into both caudate and putamen, comparable with that in patients with Parkinson's disease.

Adolescent↗
PubMed1991

Presynaptic and postsynaptic striatal dopaminergic function in neuroacanthocytosis: a positron emission tomographic study.

Using [18F]dopa, [11C]raclopride, C15O2, and positron emission tomography, we have assessed striatal dopamine storage capacity, dopamine D2-receptor integrity, and regional cerebral blood flow, respectively, of 6 patients with neuroacanthocytosis. The patients with neurocanthocytosis all had chorea and variable combinations of seizures, dementia, axonal neuropathy, and orolingual self-multiation. [18F]dopa positron emmission tomographic findings were compared with 30 normal controls and 16 patients with sporadic, L-dopa-responsive, Parkinson's disease. Caudate and anterior putamen [18F]dopa uptake were normal in patients with neuroacanthocytosis, but mean posterior putamen [18F]dopa uptake was reduced to 42% of normal, similar to that in patients with Parkinson's disease. In patients with neuroacanthocytosis, mean equilibrium caudate: cerebellum and putamen: cerebellum [11C]raclopride uptake ratios were reduced to 54% and 62% of normal, compatible with a 65% and 53% loss of caudate and putamen D2-receptor-binding sites, respectively. Striatal and frontal blood flow was also depressed. The severe loss of D2-receptor-bearing striatal neuron, with concomitant loss of dopaminergic projections from the nigra to the posterior putamen, is consistent with both chorea and extrapyramidal rigidity being features of patients with neuroacanthocytosis.

Acanthocytes↗
PubMed1991

Paroxysmal axial spasms of spinal origin.

A 55-year-old man with a 4 1/2-year history of paroxysmal bouts of involuntary large-amplitude flexion jerks of the trunk and a 1-year history of persistent rhythmic small-amplitude movements of the anterior abdominal wall is described. Clinical and electrophysiological evidence suggested that the paroxysmal myoclonus arose in propriospinal systems intrinsic to the spinal cord.

Cerebral Cortex↗
PubMed1991

Writer's cramp: treatment with botulinum toxin injections.

Twelve patients with writer's cramp were treated with injections of botulinum toxin. The overactive muscles were identified by clinical observation of the subjects while they were writing. Repeated injections were given at 2-week intervals until the optimal response was obtained. Eleven patients reported some benefit, which was considered by seven to be significant. Eight of the 10 patients who had pain reported moderate to significant relief. Five patients had local complications, consisting of disabling weakness of target or neighbouring muscles. These preliminary results suggest that this treatment can be successfully applied to many patients with writer's cramp without performing complex electromyographic recordings while the patients are writing.

Adult↗
PubMed1991

A therapeutic trial of milacemide in myoclonus and the stiff-person syndrome.

We investigated the therapeutic effects of milacemide in seven patients with myoclonus and three patients with the stiff-person syndrome in an open-label trial. Milacemide was initiated at 800 mg/day and was gradually increased to a maximum dosage of 2,400 mg/day. No significant improvement occurred in the 10 patients.

Acetamides↗