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Biomedical subjects

C D Marsden

Publications and source records attributed to C D Marsden.

At least 271 records · Page 15Linked to original sources
PubMed1994

Nigral degeneration in neuroacanthocytosis.

We counted nerve cells in different subregions of the substantia nigra in three patients with neuroacanthocytosis and compared the results with those of age-matched Parkinson's disease and control patients. Two patients with neuroacanthocytosis and clinical parkinsonism in life had a reduced neuronal density in the substantia nigra, while in a third patient without parkinsonism, this number was at the lower limit of the control range. In neuroacanthocytosis with parkinsonism and in Parkinson's disease, the ventrolateral region of the substantia nigra was most severely affected, although in neuroacanthocytosis cases, nigral neuronal loss was more widespread.

Aged↗
PubMed1994

Problems with long-term levodopa therapy for Parkinson's disease.

The introduction of levodopa 25 years ago revolutionized the management of Parkinson's disease. However, it soon became apparent that the drug offered only symptomatic relief and did not affect the underlying pathology. Moreover, chronic use of the drug was associated with a range of adverse effects. Current therapeutic strategies seek to delay long-term complications of treatment for as long as possible. However, once they appear, most adverse effects are amenable to some form of management. A number of therapeutic strategies are available for treatment of Parkinson's disease. The final choice of therapy depends on the individual circumstances and requirements of the patient and should balance tolerance for adverse effects with the amount of symptomatic relief required. Patients receiving long-term levodopa therapy must contend with some adverse effects. After 5 years the majority of these patients suffer fluctuations, dyskinesias, toxicity, or loss of efficacy. Fluctuations can be reduced by changing the drug regimen to a combination therapy of Sinemet and Sinemet controlled-release (CR), or by the addition of deprenyl or a dopamine agonist. Variations in gastric emptying and absorption of levodopa and dietary factors become important. Dyskinesias in long-term levodopa therapy are poorly understood and difficult to manage, although dopamine agonists can be of some use. As the disease progresses, new disabilities appear that are less responsive to levodopa, and its efficacy can appear to diminish, with increased doses often leading to toxicity.

Cognition Disorders↗
PubMed1993

Parallel alterations in Met-enkephalin and substance P levels in medial globus pallidus in Parkinson's disease patients.

Met-enkephalin (Met-enk) and substance P (SP) were measured by a combined high-performance liquid chromatography/radioimmunoanalysis method in medial (GPM) and lateral globus pallidus (GPL) from controls and from Parkinson's disease (PD) patients. All patients showed a similar marked (> 90%) reduction in dopamine (DA) levels in putamen compared with controls. However, based on DA levels in the caudate nucleus, two subgroups of PD patients were differentiated. In patients with > 80% decrease in caudate nucleus DA content, there was a three-fold increase in both Met-enk and SP levels in GPM. In contrast, in patients showing an approximately 50% reduction in DA content in caudate, levels of both peptides were markedly reduced (approximately 80%). Met-enk and SP levels in GPL were unchanged in PD. These results suggest that neurons containing Met-enk and SP projecting to GPM adapt according to the extent of degeneration in the substantia nigra in PD.

Aged↗
PubMed1993

Age-related effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment of common marmosets.

The effect of treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on juvenile (6-8 months), young adult (2-4 years) and aged (8-10 years) common marmosets were compared. Juvenile marmosets were more resistant to the actions of MPTP and required a greater cumulative dose over a longer period to induce the same degree of motor disability observed in older animals. Young adult and aged marmosets showed an equivalent motor recovery in the 4-5 weeks following cessation of MPTP treatment, but juvenile animals were less able to compensate for the motor impairments. Losses of putamen [3H]dopamine uptake and caudate nucleus dopamine content were equivalent in young adult and aged animals. However, juvenile animals showed a more marked degree of dopamine depletion and reduction in [3H]dopamine uptake. Histological analysis showed cell loss in the substantia nigra to be most prominent in juvenile animals although it was evident in all groups. No loss of cells in the locus coeruleus was apparent in any of the groups studied, and no intraneuronal eosinophilic inclusions were seen. Greater nigral cell loss and dopamine depletion were required in juvenile animals to impair motor function. The degree of behavioural recovery was less in juvenile animals than in young adult and aged marmosets. The extent of behavioural recovery appeared linked to the severity of cell loss and was not reduced in old age.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Modulation of postural wrist tremors by magnetic stimulation of the motor cortex in patients with Parkinson's disease or essential tremor and in normal subjects mimicking tremor.

The effect of magnetic brain stimulation on postural wrist tremor was studied in 10 patients with Parkinson's disease, 12 with hereditary essential tremor, and 10 normal subjects who mimicked tremor by making rapid alternating wrist movements. In all patients and normal subjects, magnetic brain stimulation over the contralateral motor cortex at an intensity approximately 10% above threshold produced the following sequence of events: (1) a small direct electromyographic (EMG) response, followed by (2) suppression of the rhythmic EMG activity responsible for the tremor, before (3) reappearance of the tremor time-locked to the stimulus. It is concluded that magnetic brain stimulation over the motor cortex can modulate the oscillatory mechanisms responsible for the generation of postural tremors. Group analysis revealed that the time to reappearance of rhythmic EMG activity varied significantly with the period of parkinsonian postural tremors, but not with the period of essential or mimicked tremors. Magnetic stimulation also significantly shortened the period of parkinsonian postural tremors, but did not influence the period of essential or mimicked tremors. These behavioral differences indicate differences in the pathophysiological mechanisms underlying parkinsonian postural tremor and essential tremor.

Adult↗
PubMed1993

A positron emission tomography study of essential tremor: evidence for overactivity of cerebellar connections.

The origin of essential tremor is unknown. Animal models have suggested that the inferior olivary nucleus may act as a tremor generator. We used positron emission tomography to study changes in regional cerebral blood flow associated with involuntary postural tremor and passive wrist oscillation in patients with essential tremor. Activation due to voluntary wrist oscillation and arm extension without tremor was studied in normal control subjects. The essential tremor group had bilaterally increased cerebellar blood flow at rest (without tremor) compared with the control group. Involuntary postural tremor was associated with further bilateral cerebellar activation, and also contralateral striatal, thalamic, and sensorimotor cortex activation. Voluntary wrist oscillation, maintained arm extension without tremor, and passive wrist oscillation were all associated with significant ipsilateral rather than bilateral cerebellar activation. We conclude that essential tremor is associated with increased bilateral cerebellar activity both at rest and during tremor.

Adult↗
PubMed1993

Familial parkinsonism with depression: a clinicopathological study.

A family with autosomal dominant inheritance of an early-onset and rapidly progressive parkinsonian syndrome and associated severe depression is reported. Three members had parkinsonism with depression, 3 had parkinsonism alone, and 2 suffered depression only. Pathological brain examination in 2 members with parkinsonism and depression revealed distinctive changes, with devastation of the substantia nigra, scarce Lewy bodies, and gliosis of the caudate nucleus and globus pallidus. The clinical and pathological findings were similar to those in four previously described families with autosomal dominant parkinsonism, depression, and alveolar hypoventilation.

Adult↗
PubMed1993

Effectiveness of piracetam in cortical myoclonus.

Twenty-one patients with disabling spontaneous, reflex, or action myoclonus due to various causes, who had shown apparent clinical improvement on introduction of piracetam, entered a placebo-controlled double-blind crossover trial of piracetam (2.4-16.8 g daily). All but one patient had electrophysiological evidence of cortical myoclonus. Patients were randomly allocated to a 14-day course of piracetam followed by identical placebo, or placebo followed by piracetam. Nineteen patients received piracetam/placebo in addition to their routine antimyoclonic treatment (carbamazepine, clonazepam, phenytoin, primidone, sodium valproate, or tryptophan plus isocarboxazid, alone or in combination) and two received piracetam/placebo as monotherapy. All patients were rated at the end of each treatment phase using stimulus sensitivity, motor, writing, functional disability, global assessment, and visual analogue scales. Ten of the 21 patients had to be rescued from the placebo phase of the trial because of a severe and intolerable exacerbation of their myoclonus. No patients required rescue from the piracetam phase of the double-blind trial. When the 21 patients were considered together, there was a significant improvement in motor, writing, functional disability, global assessment, and visual analogue scores during treatment with piracetam compared with placebo. The total rating score also improved significantly with piracetam, by a median of 22%. Piracetam, usually in combination with other antimyoclonic drugs, is a useful treatment for myoclonus of cortical origin.

Adult↗
PubMed1993

Suppressive effect of L-dopa on dopamine cells remaining in the ventral tegmental area of rats previously exposed to the neurotoxin 6-hydroxydopamine.

Ever since the introduction of levo-3,4-dihydroxyphenylalanine (L-dopa) for the treatment of Parkinson's disease, there has been concern that it might accelerate the degeneration of dopamine neurones. Using rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the medial forebrain bundle (MFB), we have studied the effect of chronic L-dopa treatment on the survival of dopamine cells which remain in the ventral tegmental area (VTA) ipsilateral to a 6-OHDA lesion. Following lesion surgery, rats were treated with L-dopa and carbidopa administered in the drinking water for 27 weeks. At the end of the treatment period, the number of dopamine cells remaining in each of the lesioned and intact substantia nigra (SN) and VTA were assessed, using tyrosine hydroxylase immunohistochemistry. Chronic L-dopa treatment resulted in an apparent reduction in the number of dopamine neurones remaining in the VTA ipsilateral to the lesion, whereas it had no effect on the number of dopamine cells remaining in the intact SN and VTA. This finding suggests a possible suppressive effect in vivo of L-dopa on dopamine cells in the midbrain of adult animals that have been previously exposed to 6-OHDA.

Animals↗
PubMed1993

The syndrome of gait ignition failure: a report of six cases.

The syndrome of gait ignition failure is described in six patients in whom difficulty initiating walking was the major symptom. The gait had elements of parkinsonism with start and turn hesitation, shuffling, and freezing. Unlike parkinsonism, however, the gait was relatively normal once entrained; the posture was upright, and good arm swing, a normal stride length, and no festination were seen. Equilibrium was normal or near normal, and when seated or lying, rhythmic leg movements were generated normally. Facial expression, upper limb mobility, and whole body movements were well-preserved. This gait disorder differed from that seen in Parkinson's disease and the so-called "frontal" or "senile" disorders of gait and gait "apraxia." The causes of this gait syndrome are not clear but it may be due to frontal lobe vascular disease and/or focal degeneration of the frontal lobes.

Aged↗
PubMed1993

Linkage analysis with chromosome 9 markers in hereditary essential tremor.

Hereditary essential tremor (ET) is an autosomal dominant disorder with variable expression and reduced penetrance. A tremor indistinguishable from ET may be observed in patients with autosomal dominant idiopathic torsion dystonia (ITD), in which the disease locus has been mapped to 9q32-34 in some kindreds, tightly linked to the argininosuccinate synthetase (ASS) locus. We performed linkage analysis in 15 families with ET containing 60 definitely affected individuals, using dinucleotide repeat polymorphisms at the ASS locus and the Abelson locus (ABL). Cumulative lod scores were -19.5 for ASS and -10.8 for ABL at a recombination fraction of 0.01, and tight linkage to ASS was excluded individually in 11 of the families. These data indicate that the ET gene is not allelic to that causing ITD.

Adolescent↗
PubMed1993

Alterations in striatal and extrastriatal D-1 and D-2 dopamine receptors in the MPTP-treated common marmoset: an autoradiographic study.

In adult common marmosets (Callithrix jacchus), MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) treatment induced almost total depletion of cells in the substantia nigra pars compacts (SNc) but partial cell loss in the ventral tegmental area (VTA). There was severe depletion of [3H]-mazindol binding to dopamine (DA) uptake sites in the caudate, putamen, and SNc. The loss of [3H]-mazindol binding in the nucleus accumbens (NAc) and olfactory tubercle (OT) was less marked. [3H]-mazindol binding in the body of caudate nucleus showed a small but significant recovery with increasing post-lesion survival times. The specific binding of [3H]-SCH 23390 to D-1 DA receptor sites was increased after MPTP treatment in all subregions of both caudate and putamen but was unaltered in the NAc and OT. Substantia nigra pars reticulata (SNr), frontal cortex, and medial segment of globus pallidus (GPm) all demonstrated moderate levels of [3H]-SCH 23390 binding in control animals, which were unaffected by MPTP treatment. Specific [3H]-spiperone binding to D-2 DA receptor sites was not altered by MPTP treatment in the subregions of caudate-putamen. Moderate levels of [3H]-spiperone binding were observed in control animals in the NAc, OT, SNc, and the lateral segment of globus pallidus (GP1). [3H]-spiperone binding in the SNc and OT was partially decreased in MPTP-treated animals. The changes in specific [3H]-spiperone and [3H]-SCH 23390 binding induced by MPTP-treatment did not alter with post-lesion survival times. These results demonstrate that MPTP treatment causes greater dopaminergic denervation of the caudate-putamen than in NAc/OT. This resulted in an increase in postsynaptic D-1 DA receptor sites in the caudate-putamen but not in the NAc/OT. Also, there appeared to be loss of presynaptic D-2 DA receptor sites in the SNc and OT. In the caudate-putamen, the loss of presynaptic D-2 DA receptor sites may have masked postsynaptic D-2 DA receptor upregulation.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1993

Evidence for locus heterogeneity in autosomal dominant torsion dystonia.

Idiopathic torsion dystonia (ITD) is most commonly an autosomal dominant disorder with reduced penetrance and variable expression. A locus on the distal long arm of chromosome 9 has been identified in one large non-Jewish and several Jewish families in the United States. Linkage analysis in a large Australian kindred with ITD, also containing two patients with Wilson's disease, excludes a locus for ITD in chromosome 9q34 or the region of chromosome 13 containing the Wilson disease gene. This study provides evidence for locus heterogeneity in autosomal dominant ITD and also gives additional information on gene order in chromosome 9q.

Adolescent↗
PubMed1993

Postural electromyographic responses in the arm and leg following galvanic vestibular stimulation in man.

Application of a small (around 1 mA), constant electric current between the mastoid processes (galvanic stimulation) of a standing subject produces enhanced body sway in the approximate direction of the ear behind which the anode is placed. We examined the electromyographic (EMG) responses evoked by such stimulation in the soleus and in the triceps brachii muscles. For soleus, subjects stood erect, with their eyes closed, leaning slightly forward. The head was turned approximately 90 degrees to the right or left relative to the feet. In averaged records (n = 40), current pulses of 25 ms or longer modulated the EMG in a biphasic manner: a small early component (latency 62 +/- 2.4 ms, mean +/- SEM) was followed by a larger late component (latency 115 +/- 5.2 ms) of opposite sign, which was appropriate to produce the observed body sway. The early component produced no measurable body movement. Lengthening the duration of the stimulus pulse from 25 to 400 ms prolonged the late component of the response but had little effect on the early component. Short- and long-latency EMG responses were also evoked in the triceps brachii muscle if subjects stood on a transversely pivoted platform and had to use the muscle to maintain their balance in the anteroposterior plane by holding a fixed handle placed by the side of their hip. The latency of the early component was 41 +/- 2.6 ms; the latency of the late component was 138 +/- 4.3 ms and was again of appropriate sign for producing the observed body sway. Galvanic stimulation evoked no comparable responses in either triceps brachii or soleus muscles if these muscles were not being used posturally.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Electromyographical differentiation of the components of perioral movements induced by SKF 38393 and physostigmine in the rat.

Facial electromyography (EMG) coupled with visual observation was used to investigate spontaneous and drug induced perioral movements in freely moving rats. Four separate perioral behaviours were identified; facial tremor, purposeless chewing, gaping and yawning. Facial tremor, yawning and gaping but not purposeless chewing produced characteristic EMG signals. Normal rats displayed a low level of purposeless chewing, occasional bursts of facial tremor but not gaping or yawning. Each burst of facial tremor was accompanied by a transient increase in purposeless chewing. Administration of the D1 agonist SKF 38393 induced a dose related increase in bursts of facial tremors and consequently an increase in the total number of purposeless chews. Gaping and yawning were not induced by SKF 38393 administration. Administration of the cholinesterase inhibitor physostigmine (0.1-0.4 mg/kg) induced a dose related increase in the total number of purposeless chews, but primarily these were not associated with facial tremor. Administration of physostigmine also increased gaping and yawning. Administration of the D1 antagonist SCH 23390 almost abolished facial tremor in normal treated rats but only partially reduced that induced by SKF 38393 and physostigmine. SCH 23390 reduced purposeless chewing in SKF 38393 treated rats but not in normal or physostigmine treated animals. Administration of the cholinergic antagonist atropine almost abolished facial tremor in normal and physostigmine treated rats, but only reduced by 46% that induced by SKF 38393. Atropine reduced purposeless chewing in normal, physostigmine and SKF 38393 treated animals. Physostigmine induced gaping and yawning were abolished by atropine administration.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

Effect of chronic trifluoperazine administration and subsequent withdrawal on the production and persistence of perioral behaviours in two rat strains.

The effect of chronic administration of trifluoperazine on the perioral movement profile of Wistar and Sprague-Dawley rats was examined. Perioral movements were characterised by visual observations, coupled with electromyographic recording from the masseter muscle. In drug-naive animals from both strains the spectrum of perioral behaviours was essentially identical, primarily consisting of purposeless chewing, accompanied by occasional bursts of facial tremor and teeth chattering, with occasional yawning. Each burst of facial tremor was accompanied by a transient increase in the rate of purposeless chewing. Wistar rats exhibited a higher level of spontaneous purposeless chewing compared to Sprague-Dawley rats. In both strains, chronic administration of trifluoperazine (5 mg/kg per day, PO) for 5 months induced an increase in perioral behaviour, which primarily consisted of enhanced purposeless chewing. In Wistar rats the drug-induced increase in purposeless chewing was accompanied by an increase in the incidence of yawning, with no change in the incidence of either facial tremor or teeth chattering. In contrast, Sprague-Dawley rats displayed a drug-induced increase in purposeless chewing, accompanied by an increase in the incidence of facial tremor and teeth chattering, but not yawning. In Wistar rats withdrawal of trifluoperazine diminished but did not reverse the drug-induced increase in purposeless chewing. Drug withdrawal also precipitated a transient increase in the incidence of facial tremor and teeth chattering, but had no effect on yawning. In Wistar rats, the level of purposeless chewing and the incidence of yawning remained elevated above control levels for at least 13 weeks after drug withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗