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Biomedical subjects

C D Marsden

Publications and source records attributed to C D Marsden.

At least 487 records · Page 27Linked to original sources
PubMed1989

Increased nigral iron content and alterations in other metal ions occurring in brain in Parkinson's disease.

Levels of iron, copper, zinc, manganese, and lead were measured by inductively coupled plasma spectroscopy in parkinsonian and age-matched control brain tissue. There was 31-35% increase in the total iron content of the parkinsonian substantia nigra when compared to control tissue. In contrast, in the globus pallidus total iron levels were decreased by 29% in Parkinson's disease. There was no change in the total iron levels in any other region of the parkinsonian brain. Total copper levels were reduced by 34-45% in the substantia nigra in Parkinson's disease; no difference was found in the other brain areas examined. Zinc levels were increased in substantia nigra in Parkinson's disease by 50-54%, and the zinc content of the caudate nucleus and lateral putamen was also raised by 18-35%. Levels of manganese and lead were unchanged in all areas of the parkinsonian brain studied when compared to control brains, except for a small decrease (20%) in manganese content of the medial putamen. Increased levels of total iron in the substantia nigra may cause the excessive formation of toxic oxygen radicals, leading to dopamine cell death.

Aged↗
PubMed1989

Basal lipid peroxidation in substantia nigra is increased in Parkinson's disease.

Polyunsaturated fatty acid (PUFA) levels (an index of the amount of substrate available for lipid peroxidation) were measured in several brain regions from patients who died with Parkinson's disease and age-matched control human postmortem brains. PUFA levels were reduced in parkinsonian substantia nigra compared to other brain regions and to control tissue. However, basal malondialdehyde (MDA; an intermediate in the lipid peroxidation process) levels were increased in parkinsonian nigra compared with other parkinsonian brain regions and control tissue. Expressing basal MDA levels in terms of PUFA content, the difference between parkinsonian and control substantia nigra was even more pronounced. Stimulating MDA production by incubating tissue with FeSO4 plus ascorbic acid, FeSO4 plus H2O2, or air alone produced lower MDA levels in the parkinsonian substantia nigra, probably reflecting the lower PUFA content. These results may indicate that an increased level of lipid peroxidation continues to occur in the parkinsonian nigra up to the time of death, perhaps because of continued exposure to excess free radicals derived from some endogenous or exogenous neurotoxic species.

Aged↗
PubMed1989

A selective increase in particulate superoxide dismutase activity in parkinsonian substantia nigra.

The total activity of superoxide dismutase (SOD) and cytosolic and particulate activity of SOD in human substantia nigra and cerebellum were measured by a spectrophotometric method based on the ability of SOD to inhibit the autoxidation of adrenaline. The cytosolic and particulate isoenzymes of SOD were differentiated by the inclusion of potassium cyanide which selectively inhibits cytosolic copper/zinc-dependent SOD activity. In autopsied human brains, there was no difference in total SOD activity, or the activity of SOD in cytosol in substantia nigra of patients dying with Parkinson's disease compared to age-matched controls. However, the activity of the particulate form of SOD was higher in the parkinsonian substantia nigra compared to control tissue. In the cerebellum there was no difference in the total, cytosolic, or particulate activity of SOD between parkinsonian patients and age-matched controls. Increased activity of SOD in particulate fraction may be a protective response to elevated levels of toxic free radicals in the parkinsonian substantia nigra. Alternatively, increased SOD activity may induce cell death through the accumulation of hydrogen peroxide.

Aged↗
PubMed1989

Definition of the in-vivo binding of [3H]spiperone in rat brain using substituted benzamide drugs.

The ability of some substituted benzamide drugs to define in-vivo the binding of [3H]spiperone to brain dopamine receptors in rats was assessed using behaviourally effective doses in comparison with haloperidol. As judged using haloperidol, [3H]spiperone identified dopamine receptors in the substantia nigra, striatum, tuberculum olfactorium and hypothalamus, but not in frontal cortex or nucleus accumbens. The substituted benzamide compounds alizapride, metoclopramide, clebopride and YM 09151-2 prevented the accumulation of [3H]spiperone in the substantia nigra, striatum, tuberculum olfactorium and hypothalamus. However, YM 09151-2 also caused displacement of [3H]spiperone accumulation in the nucleus accumbens and frontal cortex. (+/- )-Sulpiride, (+/- )-sultopride, amisulpiride and prosulpride all prevented the accumulation of [3H]spiperone in the hypothalamus but were ineffective in one or more of the other regions containing dopamine receptors defined by [3H]spiperone. The isomers of sulpiride and sultopride stereoselectively defined the accumulation of [3H]spiperone in dopamine containing brain regions. The (-)-isomers of both drugs prevented the accumulation of [3H]spiperone in the substantia nigra, striatum, tuberculum olfactorium and hypothalamus. In contrast, (+)-sulpiride and (+)-sultopride were ineffective. Selected substituted benzamide drugs can be used to define the interaction of ligands with dopamine receptors in-vivo. These substances may be useful in PET studies in man. The isomers of some substituted benzamine drugs may be used to define dopamine receptors in-vivo by enantiomeric selectivity.

Amisulpride↗
PubMed1989

Electric and magnetic stimulation of human motor cortex: surface EMG and single motor unit responses.

1. The effects of different forms of brain stimulation on the discharge pattern of single motor units were examined using the post-stimulus time histogram (PSTH) technique and by recording the compound surface electromyographic (EMG) responses in the first dorsal interosseous (FDI) muscle. Electrical and magnetic methods were used to stimulate the brain through the intact scalp of seven normal subjects. Electrical stimuli were applied either with the anode over the lateral central scalp and the cathode at the vertex (anodal stimulation) or with the anode at the vertex and the cathode lateral (cathodal stimulation). Magnetic stimulation used a 9 cm diameter coil centred at the vertex; current in the coil flowed either clockwise or anticlockwise when viewed from above. 2. Supramotor threshold stimuli produced one or more narrow (less than 2 ms) peaks of increased firing in the PSTH of all thirty-two units studied. Anodal stimulation always produced an early peak. The latencies of the peaks produced by other forms of stimulation, or by high intensities of anodal stimulation, were grouped into four time bands relative to this early peak, at intervals of -0.5 to 0.5, 1-2, 2.5-3.5 and 4-5.5 ms later. Peaks occurring within these intervals are referred to as P0 (the earliest anodal), P1, P2 and P3 respectively. 3. At threshold, anodal stimulation evoked only the P0 peak; at higher intensities, the P2 or more commonly the P3 peak also was recruited. The size of the P0 peak appeared to saturate at high intensities. 4. In five of six subjects, cathodal stimulation behaved like anodal stimulation, except that there was a lower threshold for recruitment of the P2 or P3 peak relative to that of the P0 peak. In the other subject, the P3 peak was recruited before the P0 peak. 5. Anticlockwise magnetic [corrected] stimulation, at threshold, often produced several peaks. These always included a P1 peak, and usually a P3 peak. A P0 peak in the PSTH was never produced by an anticlockwise stimulation [corrected] at intensities which we could explore with the technique. 6. Clockwise magnetic [corrected] stimulation never recruited a P1 peak; in most subjects a P3 peak was recruited first and at higher intensities was accompanied by P0 or P2 peaks. 7. On most occasions when more than one peak was observed in a PSTH, the unit fired in only one of the preferred intervals after each shock. However, double firing was seen in five units when high intensities of stimulation were used.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1989

Does signal-attenuation on high-field T2-weighted MRI of the brain reflect regional cerebral iron deposition? Observations on the relationship between regional cerebral water proton T2 values and iron levels.

T2-weighted MRI shows attenuated signals from the basal ganglia, such signal attenuation being more evident at high magnetic field strengths of 1.5 tesla (T). The basal ganglia contain high levels of iron, and it has been suggested that these iron deposits lead to shortening of bulk water T2 protons via a mechanism involving diffusion of water through local magnetic field gradients generated by the iron. This mechanism generates a relaxation contribution that is proportional to the square of the applied static field B0, and if it is significant the relaxation rate 1/T2 should be strongly dependent on Bo. T2-weighted MRI would then provide a potential means of imaging regional cerebral iron levels at field strengths that are high enough for this mechanism to be important. The bulk water proton spin-spin relaxation times (T2) of samples from caudate nucleus, frontal cortex, and white matter, taken from fresh cerebral necropsy material of four subjects dying of non-neurological conditions, and one subject with Parkinson's disease have been measured. T2 values were compared with regional cerebral iron content. At high field strengths (2.35 T and 8.5 T) no significant variation in regional cerebral water proton T2 values was found; caudate, cortex and white matter had similar water proton spin-spin relaxation times in spite of the variation in their iron content. Increasing the field strength from 2.35 T to 8.5 T resulted in a generalised 50% decrease in mean regional cerebral T2 values, as opposed to the 13-fold decrease expected if T2 relaxation was dominated by a mechanism that is dependent on B02. It was thus not possible to provide evidence that iron deposition per se is responsible for the attenuated signal obtained from the basal ganglia in T2-weighted MRI.

Body Water↗
PubMed1989

Tyrosine hydroxylase and levodopa responsive dystonia.

It has been suggested that a form of inherited dystonia responsive to levodopa might be due to an abnormality of tyrosine hydroxylase gene. This hypothesis has been tested using a cDNA tyrosine hydroxylase gene probe in three families with this disorder. No evidence for genetic linkage between the disease and tyrosine hydroxylase loci was found; it is possible that the disorder results from a post-transcriptional defect confined to the brain.

Chromosome Mapping↗
PubMed1989

Vestibulo-ocular abnormalities in spasmodic torticollis before and after botulinum toxin injections.

In order to establish whether vestibular abnormalities often found in spasmodic torticollis are secondary to the abnormal head posture, the vestibulo-ocular reflex (VOR) was studied in eight patients before and after correction of head posture with botulinum toxin. Eye movements were recorded in the dark during sinusoidal and velocity step rotation. Four patients showed a significantly asymmetric response, with the slow phase of the VOR more active ipsilateral to the torticollis (chin). Despite significant improvement of the head posture in all patients for up to 10 weeks following treatment, no correction of the vestibular asymmetry occurred. This suggests that the VOR abnormalities are not caused by the head posture itself. We interpret the findings as evidence of primary involvement of the vestibular system in torticollis and we postulate a widespread derangement of the sensory-motor mechanisms controlling head posture in this disease.

Adult↗
PubMed1989

Magnetic stimulation over the spinal enlargements.

Magnetic stimulation over the cervical and lumbar spinal enlargements was performed in 10 normal volunteers using a 9 cm diameter coil. Although the threshold and the amplitude of responses depended on the position of the coil and the direction of current flow within it, the latency was constant. The latencies obtained by magnetic stimulation were compatible with those obtained using high voltage electrical stimulation of the spinal nerve roots and always were shorter than the peripheral motor conduction time estimated by F-wave techniques. The site of activation by magnetic stimulation appears to be very similar to that stimulated by the high-voltage electrical method. Stimulation of descending motor tracts within the cord was not possible using the magnetic stimulator.

Action Potentials↗
PubMed1989

Rapid elbow movements in patients with torsion dystonia.

Rapid, self paced and self terminated elbow flexion movements were studied in a group of 10 patients with dystonia affecting the arms. The movements were slower and for small amplitude movements, more variable than those recorded in normal subjects. The duration of the first agonist burst was prolonged, even when compared with normal subjects deliberately moving slowly. Cocontraction of agonist and antagonist muscles during ballistic movements was common and may contribute to the bradykinesia. These findings are compared with similar studies of other diseases of the motor system. Unlike many other conditions which also reduce the speed of ballistic voluntary movements, the patients with dystonia in the present study showed a normal symmetry of acceleration and deceleration times. One interpretation of this finding is that aspects of the basic motor programmes are relatively preserved in this condition and account for the surprising retention of motor skills shown by some patients with dystonia.

Adolescent↗
PubMed1989

An exteroceptive reflex in the sternocleidomastoid muscle produced by electrical stimulation of the supraorbital nerve in normal subjects and patients with spasmodic torticollis.

We examined suppression of EMG activity in the contracting sternocleidomastoid muscles, produced by electrical stimulation of the supraorbital nerve in 10 normal subjects and 9 patients with spasmodic torticollis. This exteroceptive reflex in the sternocleidomastoid muscle consisted of 2 or 3 phases: (1) an early, small, and unstable phase of facilitation, followed by (2) a period of suppression beginning 35 msec after the stimulus, lasting for 35 msec with a reduction in EMG activity to approximately 40% of the prestimulus level, and (3) a further phase of facilitation at a latency of 70 msec, with duration 35 msec and an increase in EMG activity to approximately 35% above prestimulus levels. The latency and duration of the suppressive phase of this reflex were similar to the exteroceptive suppression of EMG activity in the masseter muscle after supraorbital nerve stimulation (masseter silent period). In patients with spasmodic torticollis, the depth of this exteroceptive suppression in the sternocleidomastoid muscles was less than that observed in an age-matched cohort of normal subjects, although the latency and duration were normal. In contrast, exteroceptive suppression in the masseter muscle was normal. These findings suggest abnormal function of inhibitory interneuronal networks between the 5th cranial nerve and the motor neurons of the spinal accessory and upper cervical nerves which mediate exteroceptive suppression in the sternocleidomastoid muscle in patients with spasmodic torticollis.

Adult↗
PubMed1989

[Percutaneous electric and magnetic stimulation of the motor cortex in man. Physiological aspects and clinical applications].

The new techniques of percutaneous electric and magnetic stimulation of the motor cortex in conscious man provide a unique opportunity of functional testing of the central motor pathways. These techniques seem to be safe and no immediate or delayed adverse reactions have been reported. The physiological studies so far performed suggest that the structures which are preferentially excited by these methods are the fast conducting pyramidal neurones. It has been shown that a single cortical stimulus is able to activate spinal motoneurones repeatedly. This phenomenon can easily be explained if the cortical stimulus generates multiple descending volleys in the central motor pathways. By comparison with experiments of stimulation of the exposed motor cortex in animals, it is likely that electric brain stimulation directly activates the axons of the pyramidal neurons at their origin and to a lesser extent also recruits these neurons transsynaptically, via some cortical interneurones. Magnetic stimulation of the brain at the vertex seems to act mostly by the latter mechanism. These different modes of action of the two methods of cortical stimulation explain the latency differences of the EMG responses obtained with either technique. Increased excitability of the spinal motoneurones and the existence of multiple descending volleys in response to a single cortical stimulus result in shortening of the latencies and greater amplitude of the responses recorded during voluntary contraction of the target muscle. Stimulation of the motor cortex has been used in pilot studies conducted on patients suffering from various disorders of the central motor pathways, such as multiple sclerosis, cervical spondylosis, motor neurone disease or stroke. The sensitivity of the technique looks promising. In M.S., the EMG responses usually show an increased central conduction latency, a reduced amplitude and a prolonged duration. The severity of the electrophysiological abnormalities is not very well correlated with clinical weakness, but the correlations seems to be better with hyperreflexia and the presence of brisk finger flexor jerks. The same abnormalities are observed in cervical spondylosis, although to a lesser extent. In motor neurone disease, the responses have a moderately increased latency and their size and duration are markedly reduced. Patients with acute hemispheric stroke usually show absent responses on the contralateral side. Finally, electric cortical stimulation can be very useful in monitoring the functional integrity of descending motor tracts during surgical operations performed on the spinal cord.

Central Nervous System Diseases↗