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Biomedical subjects

C D Marsden

Publications and source records attributed to C D Marsden.

At least 289 records · Page 16Linked to original sources
PubMed1993

Visuospatial memory deficits at different stages of Parkinson's disease.

Groups of patients with idiopathic Parkinson's disease (PD), either medicated or unmedicated, were compared with matched groups of normal controls on a computerised battery of tests designed to investigate spatial working memory, visuospatial recognition memory and learning. The medicated PD patients were subdivided into those with mild and severe clinical disability on the basis of Hoehn and Yahr ratings, thus making three groups of PD patients in all. In a test of spatial recognition memory, a significant impairment was only evident in those PD patients who were medicated and had severe clinical symptoms (Hoehn and Yahr stage III-IV). In contrast, none of the three patient groups were impaired in a complementary test of visual pattern recognition memory. Whilst all three patient groups performed well in a test of simultaneous visual matching to sample, medicated patients (MED PD) with severe clinical symptoms were significantly impaired when a short (0-12 sec) delay was introduced. In a test of paired associates learning requiring both visual pattern and visuospatial memory, deficits in learning and memory were only evident in the severely impaired MED PD group. In contrast, in a test of spatial working memory known to be sensitive to frontal lobe damage, significant impairments were found in both groups of medicated PD patients and particularly in those patients with more severe clinical symptoms. Taken together, the results suggest that there are multiple memory impairments in PD which may differentially depend on the clinical severity of the disease.

Aged↗
PubMed1993

Transcranial electric and magnetic stimulation of the leg area of the human motor cortex: single motor unit and surface EMG responses in the tibialis anterior muscle.

We compared single motor unit and surface EMG responses in the active right tibialis anterior following anodal electrical or magnetic stimulation of the motor cortex over the vertex. Magnetic stimulation used a monophasic current pulse through a circular coil centred 3 cm anterior to the vertex. Lowest threshold magnetic stimulation occurred when the current in the coil flowed from the left to the right side at the posterior rim of the coil. Such stimulation produced single unit and surface EMG responses which had the same latency as those produced by anodal electric stimulation. If the direction of the magnetic stimulating current was reversed, response latencies became more variable from unit to unit, and on average they occurred 1.0 +/- 0.5 msec later. In single motor units anodal and magnetic post-stimulus time histogram (PSTH) peaks had the same duration. This was similar to the duration of the PSTH peaks produced by a single low intensity stimulus given to the common peroneal nerve. We conclude that magnetic stimulation can produce direct activation of corticospinal neurones to the tibialis anterior if the direction of induced current flow is optimal. This projection is likely to be either monosynaptic or oligosynaptic.

Adult↗
PubMed1993

Some saccadic eye movements can be delayed by transcranial magnetic stimulation of the cerebral cortex in man.

In 15 normal subjects we investigated the effect on visually guided saccadic eye movements of giving a single transcranial magnetic stimulus through a circular coil centered at the vertex. In the normal paradigm, subjects fixated a target which moved randomly to the left or right by 11 degrees. The mean saccadic reaction time of 189 ms was increased by 40-50 ms if a magnetic stimulus was given in random trials some 60 ms prior to the expected onset time of control saccades. The duration and amplitude of the saccades was unchanged. The delay was smaller if the stimulus was given earlier in the reaction period, or if the coil was moved anterior or posterior to the vertex. Larger stimulus intensities produced longer delays. Three subjects were trained to produce express saccades (mean saccadic reaction times of 107-141 ms) in a 'gap' paradigm. The latency of these saccades, which are thought to be mediated by collicular mechanisms without involvement of the cortex, was not affected by magnetic stimulation. This suggests that magnetic stimulation delays normal visually guided saccades by an action on the cerebral cortex, rather than on the oculomotor centres of the brainstem. Five subjects made non-targeted saccades in darkness in response to an auditory stimulus. These saccades, like visually guided saccades, could be delayed by magnetic brain stimulation. We conclude that saccadic delay is produced by interference with cortical areas involved in the execution of saccades rather than by interfering with the perception of the visual or auditory 'go' stimulus. These probably include supplementary and frontal eye field and posterior parietal cortex. The fact that visually guided saccades emerged intact after the delay indicates that the instructions for amplitude and direction were stored separately from those involved in timing when the movement was to occur.

Acoustic Stimulation↗
PubMed1993

Linkage analysis in British and French families with idiopathic torsion dystonia.

Idiopathic torsion dystonia is most commonly caused by an autosomal dominant gene or genes with reduced penetrance. An idiopathic torsion dystonia locus has been mapped to chromosome 9q34 in one large non-Jewish and several Jewish kindreds in the USA. Linkage analysis was performed in 27 (26 British, one French) small families with idiopathic torsion dystonia, three of which were Ashkenazi Jewish, using the highly polymorphic loci argininosuccinate synthetase (ASS) and Abelson oncogene (ABL) which map to 9q34. The cumulative lod score for the more informative ASS locus at a recombination fraction of 0.001 was -6.72. A large component of this score was derived from three non-Jewish families, indistinguishable clinically from the others, in which individual lod scores excluded a disease locus tightly linked to ASS. Analysis of all the data using HOMOG showed significant heterogeneity, but evidence for linkage of an idiopathic torsion dystonia gene to 9q34 in a subset of families. The allelic association observed between ASS/ABL and idiopathic torsion dystonia in Ashkenazi families in the USA was also present in British Jewish kindreds. These data suggest genetic heterogeneity in idiopathic torsion dystonia but indicate the existence of a locus for idiopathic torsion dystonia at 9q34 in both Jewish and non-Jewish kindreds in the UK.

Argininosuccinate Synthase↗
PubMed1993

The causalgia-dystonia syndrome.

We report 18 patients (16 women and two men) with causalgia and dystonia, triggered by peripheral injuries in 15 cases and occurring spontaneously in three. The injury was often trivial, and did not cause overt peripheral nerve lesions. The mean age at presentation was 28.5 years. None had a family history of dystonia. The leg was affected initially in 12 patients, the arm in the remaining six cases. All had burning pain, allodynia and hyperpathia, along with vasomotor, sudomotor and trophic changes. All developed dystonic muscle spasms in the affected part. Dystonia always appeared at the same time or after the causalgia. The spasms were typically sustained, producing a 'fixed' dystonic posture, in contrast to the mobile spasms characteristics of idiopathic torsion dystonia. There was spread of the causalgia and of the dystonia from its initial site both in the affected limb and to other extremities, the latter in hemiplegic, transverse and triplegic distribution. All investigations were normal. All modes of conventional treatment failed to relieve either the pain or the dystonia, but two patients recovered spontaneously. At present it is impossible to decide whether this distressing syndrome is a true functional disorder of the central nervous system, or is of psychogenic origin.

Adolescent↗
PubMed1993

Response choice in Parkinson's disease. The effects of uncertainty and stimulus-response compatibility.

Reaction time paradigms provide a set of methods for assessing aspects of the planning and execution of voluntary movements in Parkinson's disease. Attention has focused mainly on the issue of programming of responses, employing a combination of simple reaction time (SRT) and choice reaction time (CRT) paradigms. The first part of the present study replicated an earlier finding in which patients showed a disproportionate slowing in CRT compared with SRT. The main aim of the study was to investigate the possible role of response choice, a key stage prior to motor programming in this CRT deficit. Two factors were manipulated: (i) response uncertainty and (ii) stimulus-response compatibility. The patients showed a normal increase in reaction time with increasing uncertainty in the compatible conditions, and a normal response to stimulus-response compatibility in the two-choice task. However, the two groups showed qualitatively different patterns of interaction between the two experimental factors, with only the patients showing a disproportionate slowing with incompatible stimulus-response relationships in the four-choice task. The data were interpreted in terms of Hasbroucq et al.'s (1990) list-rule model of stimulus-response compatibility effects, which suggested that the patients and controls were using different strategies for dealing with incompatible stimulus-response relationships. The use of different strategies makes it impossible to determine whether or not the processing of the patients is impaired in Parkinson's disease, although further research is suggested to clarify the question. However, the present data suggest that any impairment in response choice is unlikely to contribute to the slowing in CRT in Parkinson's disease under conditions of high stimulus-response compatibility.

Aged↗
PubMed1993

Vestibular induced postural responses in Parkinson's disease.

We have tested the hypothesis that dysfunction of the vestibular control of posture is a principal cause of parkinsonian instability by measuring the body sway response induced by galvanic vestibular stimulation (0.5 mA for 2 s) in a group of patients with Parkinson's disease (n = 15). Responses were compared with those obtained from a group of age-matched control subjects (n = 10). Subjects were stimulated (randomized polarity) whilst standing with feet together, eyes closed and maintaining one of five head yaw angles. The motion of the body and the ground reaction forces were measured in three dimensions. There was no significant difference between patients and controls in the speed or direction of the induced body sway response. When the patients were subdivided into two groups according to a clinical assessment of postural deficit, the more disabled group was found to respond with significantly greater body speed than either the control group or the mildly affected patient group. However, the baseline speed of spontaneous body sway was also greater in these patients and it was found that response speed was linearly related to baseline body sway even for the control group. There were no significant differences between any of these groups in the latency to onset, latency to peak or peak amplitude of the initial horizontal ground reaction force response to the stimulus. We conclude that vestibular dysfunction does not explain the postural deficits of patients who are mildly or moderately affected by Parkinson's disease.

Biomechanical Phenomena↗
PubMed1993

Striatal [18F]dopa uptake in familial idiopathic dystonia.

It is known that most cases of idiopathic torsion dystonia (ITD) are inherited in an autosomal dominant fashion. Despite clarification of the underlying genetic defect, no consistent structural lesion has been identified in ITD, and it is probable that a biochemical disturbance is the basis of the disorder. To determine whether there is impaired function of the nigro-striatal dopaminergic terminals in ITD we studied 11 subjects with generalized ITD and a positive family history using [18F]dopa and PET scanning. Of these 11 patients, eight had putamen [18F]dopa uptake within the lower half of the normal range, while three had uptake reduced by > 2 SDs below the normal mean. The lowest putamen [18F]dopa influx constants were found in the most disabled patients. As these reductions were mild it is unlikely that abnormalities of the nigro-striatal dopaminergic pathway are the primary determinant of either the nature of the severity of dystonic symptoms. In addition, we studied three presumed carriers of the ITD gene. These subjects all had normal striatal [18F]dopa influx constants suggesting that [18F]dopa PET is unsuitable as a screening tool for ITD.

Adult↗
PubMed1993

Altered muscarinic and nicotinic receptor densities in cortical and subcortical brain regions in Parkinson's disease.

Muscarinic and nicotinic cholinergic receptors and choline acetyltransferase activity were studied in postmortem brain tissue from patients with histopathologically confirmed Parkinson's disease and matched control subjects. Using washed membrane homogenates from the frontal cortex, hippocampus, caudate nucleus, and putamen, saturation analysis of specific receptor binding was performed for the total number of muscarinic receptors with [3H]quinuclidinyl benzilate, for muscarinic M1 receptors with [3H]pirenzepine, for muscarinic M2 receptors with [3H]oxotremorine-M, and for nicotinic receptors with (-)-[3H]nicotine. In comparison with control tissues, choline acetyl-transferase activity was reduced in the frontal cortex and hippocampus and unchanged in the caudate nucleus and putamen of parkinsonian patients. In Parkinson's disease the maximal binding site density for [3H]quinuclidinyl benzilate was increased in the frontal cortex and unaltered in the hippocampus, caudate nucleus, and putamen. Specific [3H]pirenzepine binding was increased in the frontal cortex, unaltered in the hippocampus, and decreased in the caudate nucleus and putamen. In parkinsonian patients Bmax values for specific [3H]oxotremorine-M binding were reduced in the cortex and unchanged in the hippocampus and striatum compared with controls. Maximal (-)-[3H]nicotine binding was reduced in both the cortex and hippocampus and unaltered in both the caudate nucleus and putamen. Alterations of the equilibrium dissociation constant were not observed for any ligand in any of the brain areas examined. The present results suggest that both the innominatocortical and the septohippocampal cholinergic systems degenerate in Parkinson's disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗
PubMed1993

Chronic administration does not alter the pharmacokinetic profile of L-dopa in the rat.

Chronic administration of L-dopa (200 mg kg-1 day-1 for 12 months) plus carbidopa (25 mg kg-1 day-1) or carbidopa (25 mg kg-1 day-1) alone did not alter the t1/2, AUC0-infinity k10, k12, k21, CLp or Vdss of L-dopa following intra-aortic (i.a.) administration (50 mg kg-1) alone or after carbidopa (25 mg kg-1, i.p.) pretreatment, or the t1/2, AUC0-infinity, tmax or the bioavailability (F) of L-dopa (50 mg kg-1) administered orally, alone or after acute pretreatment with carbidopa (25 mg kg-1 i.p.). The peripheral metabolism of L-dopa was unaltered by chronic administration of L-dopa plus carbidopa or carbidopa alone as measured by unaltered AUC0-360 min for 3-O-methyldopa, dopamine, DOPAC or homovanillic acid in the plasma of rats following acute administration of L-dopa (50 mg kg-1, p.o. or i.a.) alone or following pretreatment with carbidopa, and unaltered hepatic dopa decarboxylase activity.

Administration, Oral↗
PubMed1993

Effect of vision and stance width on human body motion when standing: implications for afferent control of lateral sway.

1. Measurements of human upright body movements in three dimensions have been made on thirty-five male subjects attempting to stand still with various stance widths and with eyes closed or open. Body motion was inferred from movements of eight markers fixed to specific sites on the body from the shoulders to the ankles. Motion of these markers was recorded together with motion of the point of application of the resultant of the ground reaction forces (centre of pressure). 2. The speed of the body (average from eight sites) was increased by closing the eyes or narrowing the stance width and there was an interaction between these two factors such that vision reduced body speed more effectively when the feet were closer together. Similar relationships were found for components of velocity both in the frontal and sagittal planes although stance width exerted a much greater influence on the lateral velocity component. 3. Fluctuations in position of the body were also increased by eye closure or narrowing of stance width. Again, the effect of stance width was more potent for lateral than for anteroposterior movements. In contrast to the velocity measurements, there was no interaction between vision and stance width. 4. There was a progressive increase in the amplitude of position and velocity fluctuations from markers placed higher on the body. The fluctuations in the position of the centre of pressure were similar in magnitude to those of the markers placed near the hip. The fluctuations in velocity of centre of pressure, however, were greater than of any site on the body. 5. Analysis of the amplitude of angular motion between adjacent straight line segments joining the markers suggests that the inverted pendulum model of body sway is incomplete. Motion about the ankle joint was dominant only for lateral movement in the frontal plane with narrow stance widths (< 8 cm). For all other conditions most angular motion occurred between the trunk and leg. 6. The large reduction in lateral body motion with increasing stance width was mainly due to a disproportionate reduction in the angular motion about the ankles and feet. A mathematical model of the skeletal structure has been constructed which offers some explanation for this specific reduction in joint motion.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

Corticocortical inhibition in human motor cortex.

1. In ten normal volunteers, a transcranial magnetic or electric stimulus that was subthreshold for evoking an EMG response in relaxed muscles was used to condition responses evoked by a later, suprathreshold magnetic or electric test shock. In most experiments the test stimulus was given to the lateral part of the motor strip in order to evoke EMG responses in the first dorsal interosseous muscle (FDI). 2. A magnetic conditioning stimulus over the hand area of cortex could suppress responses produced in the relaxed FDI by a suprathreshold magnetic test stimulus at interstimulus intervals of 1-6 ms. At interstimulus intervals of 10 and 15 ms, the test response was facilitated. 3. Using a focal magnetic stimulus we explored the effects of moving the conditioning stimulus to different scalp locations while maintaining the magnetic test coil at one site. If the conditioning coil was moved anterior or posterior to the motor strip there was less suppression of test responses in the FDI. In contrast, stimulation at the vertex could suppress FDI responses by an amount comparable to that seen with stimulation over the hand area. With the positions of the two coils reversed, conditioning stimuli over the hand area suppressed responses evoked in leg muscles by vertex test shocks. 4. The intensity of both conditioning and test shocks influenced the amount of suppression. Small test responses were more readily suppressed than large responses. The best suppression was seen with small conditioning stimuli (0.7-0.9 times motor threshold in relaxed muscle); increasing the intensity to motor threshold or above resulted in less suppression or even facilitation. 5. Two experiments suggested that the suppression was produced by an action on cortical, rather than spinal excitability. First, a magnetic conditioning stimulus over the hand area failed to produce any suppression of responses evoked in active hand muscles by a small (approximately 200 V, 50 microsecond time constant) anodal electric test shock. Second, a vertex conditioning shock had no effect on forearm flexor H reflexes even though responses in the same muscles produced by magnetic cortical test shocks were readily suppressed at appropriate interstimulus intervals. 6. Small anodal electric conditioning stimuli were much less effective in suppressing magnetic test responses than either magnetic or cathodal electric conditioning shocks.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

Modulation of postural tremors at the wrist by supramaximal electrical median nerve shocks in essential tremor, Parkinson's disease and normal subjects mimicking tremor.

The response of postural wrist tremors to supramaximal median nerve stimulation was examined in patients with hereditary essential tremor (n = 10) and Parkinson's disease (n = 9), and in normal subjects mimicking wrist tremor (n = 8). The average frequency of on-going tremor was the same in all three groups. Supramaximal peripheral nerve shocks inhibited and then synchronised the rhythmic electromyographic (EMG) activity of all types of tremor. The duration of inhibition ranged from 90 to 210ms, varying inversely with the frequency of on-going tremor. There was no significant difference in mean duration of inhibition or in the timing of the first peak after stimulation on the average rectified EMG records between the three groups. The degree to which supramaximal peripheral nerve shocks could modulate the timing of rhythmic EMG bursts in the forearm flexor muscles was also quantified by deriving a resetting index. No significant difference in mean resetting index of the three groups was found. These results suggest that such studies cannot be used to differentiate between the common causes of postural wrist tremors.

Adult↗
PubMed1993

A comparative study of simple and choice reaction time in Parkinson's, Huntington's and cerebellar disease.

The aim of the study was to compare the quantitative and qualitative similarities and differences in the performance of patients with Parkinson's disease, Huntington's disease and cerebellar disease on a number of reaction time tasks. Simple reaction time (SRT), uncued and fully cued four choice (CRT) tasks were performed by eight patients with Parkinson's disease after withdrawal of dopaminergic medication for an average of 14.4 hours; by seven non-demented patients with Huntington's disease and by eight patients with cerebellar disease. An S1 (warning signal/precue)-S2 (imperative stimulus) paradigm was used in all tasks, with the S1-S2 interval randomly varying between 0, 200, 800, 1600 and 3200 ms across trials. The patients with Huntington's disease had a significantly longer SRT than those with Parkinson's disease. None of the other group differences in uncued and unwarned SRT and CRT was significant. For the patients with Parkinson's disease and those with cerebellar disease, unwarned SRT was faster than uncued and unwarned CRT. For the patients with Huntington's disease, this CRT/SRT difference was not significant. A warning signal before the imperative stimulus resulted in a reduction of reaction time in all three groups. Advance information provided by S1 about the response that would be required by S2 was used by patients in all three groups, evident from reaction times in the fully cued CRT task being faster than those in the uncued CRT condition. Patients with cerebellar disease had slower movement times in the SRT and CRT conditions compared with the patients with Parkinson's disease and Huntington's disease, whose times did not differ. In one SRT condition, when the absence of a warning signal was predictable, patients with cerebellar disease, and to a lesser extent those with Huntington's disease, were able to maintain a general motor readiness before the imperative stimulus. This was not the case for the patients with Parkinson's disease who seemed more dependent on the presence of a warning signal to reduce their reaction time. With a few exceptions, the pattern of results of the three groups were qualitatively similar. It may be concluded that similar reaction time deficits are found in Parkinson's disease, in patients with other disorders of the basal ganglia (Huntington's disease), as well as those with a disease sparing the basal ganglia (cerebellar disease). The non-specific slowness observed at the behavioural level may, however, have diverse central mechanisms.

Adult↗
PubMed1993

The execution of bimanual movements in patients with Parkinson's, Huntington's and cerebellar disease.

Patients with Parkinson's disease have difficulty in performing two different tasks simultaneously. The present study tested whether this deficit was specific to the disease or was found in other patient groups. An identical pattern of performance was shown by a group of patients with cerebellar disease and, to a lesser extent, by a group of patients with Huntington's disease. Further research should focus on clarifying the nature of the deficits and the reasons for the similar performances in the various patient groups.

Female↗
PubMed1993

The use of botulinum toxin in the treatment of adductor spasmodic dysphonia.

Botulinum toxin injections have been used to treat 31 patients with adductor spasmodic dysphonia. Injections of 3.00-3.75 units of botulinum toxin were performed bilaterally into the thyroarytenoid muscle. This treatment significantly decreased the standard deviation of the fundamental frequency of the speech sample, indicating a reduction in the variability of pitch amongst patients. A total of 96% of patients' subjective diary reports showed an improvement with a median of 7 days to peak effect and a 5 week duration of peak effect.

Adult↗
PubMed1993

Successful treatment of childhood onset symptomatic dystonia with levodopa.

Three patients with childhood onset symptomatic dystonia responded to levodopa. None fulfilled criteria for a diagnosis of "dopa responsive dystonia" (Segawa's disease). One may have had athetoid cerebral palsy for almost 25 years. All obtained dramatic and sustained benefit from levodopa therapy. A therapeutic trial of levodopa is advised in all patients in whom dystonia has developed in childhood or early adult life, regardless of suspected aetiology or duration of symptoms.

Adolescent↗