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D J Brooks

Publications and source records attributed to D J Brooks.

At least 127 records · Page 7Linked to original sources
PubMed1998

Positron emission tomography studies in movement disorders.

Positron emission tomography (PET) scanning provides a sensitive means of detecting and characterizing regional changes in brain metabolism and receptor binding in movement disorders. PET allows the quantitative examination of regional cerebral blood flow, regional glucose and oxygen metabolism, and brain pharmacology. In this article, the particular use of PET to determine the effects of therapeutic stereotactic surgery, including transplantation, on brain function in Parkinson's disease and in tremor patients is highlighted.

Humans↗
PubMed1998

Guidelines for the management of Parkinson's disease. The Parkinson's Disease Consensus Working Group.

Parkinson's disease is a chronic and disabling illness and there is currently wide variation in its management. This article presents the first UK-specific guidelines for the management of Parkinson's disease and it contains a treatment decision free to aid the physician in deciding when and how to treat patients. We hope this document will prove useful to all those involved in the planning and delivery of care to patients with Parkinson's disease.

Aged↗
PubMed1997

The effect of movement frequency on cerebral activation: a positron emission tomography study.

Knowledge of the effect of performance frequency on activation of motor areas in positron emission tomography (PET) studies is crucial to the interpretation of experiments in which performance is a variable. We studied this effect in six normal right-handed volunteers using H2(15)O PET to measure regional cerebral blood flow (rCBF). Subjects were scanned at rest and while executing joystick movements with the right hand in freely chosen directions at different frequencies. Significant frequency dependent increases in rCBF were demonstrated in contralateral sensorimotor cortex, lateral premotor cortex bilaterally, posterior supplementary motor area (SMA), and ipsilateral cerebellar hemisphere and vermis. The striatum and the right dorsal prefrontal cortex were also activated by joystick movement compared with rest, but the magnitude of activation found in these areas was independent of the frequency of movement. The results suggest that primary motor cortex, posterior SMA, lateral premotor cortex and cerebellum are involved in determining the basic parameters of movement. Frequency dependent activation in these areas suggests phasic activity related to movement. In contrast, activation of the dorsal prefrontal cortex and the striatum is not frequency dependent. This may reflect continuous rather than phasic activity in these areas during the task and suggests their role is not simply related to movement execution but higher level during this free selection joystick task.

Adult↗
PubMed1997

Stereotactic thalamotomy in tremor-dominant Parkinson's disease: an H2(15)O PET motor activation study.

Stereotactic thalamotomy is an effective treatment for severe drug-resistant tremor. The thalamus, however, facilitates motor activity, and thalamotomy would be predicted to inhibit movement-associated cortical activation. Two tremulous parkinsonian patients were studied with H2(15)O positron emission tomography before and after left ventralis intermedius thalamotomy. Subjects were scanned at rest and during performance of externally paced joystick movements in freely selected directions with the right hand. Thalamotomy relieved tremor but, as predicted, led to decreased activation of the left sensorimotor cortex, lateral premotor cortex, and parietal area 7 on hand movement.

Aged↗
PubMed1997

Dopaminergic function in familial Parkinson's disease: a clinical and 18F-dopa positron emission tomography study.

There is increasing evidence for familial aggregation in Parkinson's disease (PD). It is possible that some asymptomatic relatives of PD patients have subclinical nigral Lewy body pathology and their identification could help determine the true prevalence of the disease. We used 18F-dopa positron emission tomography to investigate nigrostriatal dopaminergic terminal function in asymptomatic members of 7 unrelated kindreds in which at least 2 members had parkinsonism. Eight (25%) of the 32 asymptomatic relatives showed abnormal putamen 18F-dopa uptake (2.5 standard deviations below the normal mean). When discriminant function analysis was applied, all of these 8 subjects plus another 3 were classified with high probability as having PD. On neurological examination, 5 of the 32 relatives scanned had an isolated mild postural tremor and 2 of these 5 had reduced putamen uptake. Our findings provide further support for a role of inheritance in the etiology of PD and suggest that the penetrance for nigrostriatal dopaminergic dysfunction in familial clusters of PD is higher than the prevalence of clinical parkinsonism reported in epidemiological surveys.

Adult↗
PubMed1997

Short- and long-term survival and function of unilateral intrastriatal dopaminergic grafts in Parkinson's disease.

Six patients with Parkinson's disease were followed for 10 to 72 months after human embryonic mesencephalic tissue from four to seven donors was grafted unilaterally into the putamen (4 patients) or putamen plus caudate (2 patients). After 8 to 12 months, positron emission tomography showed a 68% increase of 6-L-[18F]-fluorodopa uptake in the grafted putamen, no change in the grafted caudate, and minor decreases in nongrafted striatal regions. There was therapeutically valuable improvement in 4 patients, but only modest changes in the other 2, both of whom developed atypical features. Patient 4 was without L-dopa from 32 months and had normal fluorodopa uptake in the grafted putamen at 72 months. Overall, the L-dopa dose was reduced by a mean of 10 and 20%, "off" time was reduced by 34 and 44%, and the "off" phase Unified Parkinson's Disease Rating Scale motor score by 18 and 26%, and the duration of the response to a single L-dopa dose increased by 45 and 58% during the first and second years after surgery, respectively. Rigidity and hypokinesia improved bilaterally, but mainly contralateral to the implant. No consistent changes in dyskinesias were observed. We conclude that transplantation of embryonic mesencephalic tissue leads to highly reproducible survival of dopaminergic neurons, inducing clinically valuable improvements in most recipients.

Adult↗
PubMed1997

Alterations in opioid receptor binding in Parkinson's disease patients with levodopa-induced dyskinesias.

Levodopa-induced dyskinesias remain a major challenge in the therapeutic management of Parkinson's disease (PD). Their etiology is unknown although dysfunction of striatal opioid transmission has been implicated in experimental models of PD. To determine whether the opioid system is involved in human dyskinetic PD, we measured in vivo opioid receptor binding in PD patients with and without levodopa-induced dyskinesias, using positron emission tomography (PET) and the opioid receptor ligand [11C]diprenorphine. Striatal and thalamic/occipital uptake ratios were calculated using a region of interest (ROI) approach. In addition, we used statistical parametric mapping (SPM) and images reflecting the volume of distribution of [11C]diprenorphine to assess changes in cerebral receptor binding on a voxel-by-voxel basis. By using the ROI approach, we found significantly reduced striatal and thalamic opioid binding in dyskinetic, but not in nondyskinetic, PD patients. The SPM approach confirmed reduced availability in these areas and, in addition, showed decreased cingulate and increased prefrontal opioid receptor binding in the dyskinetic patients. Our findings confirm that altered opioid transmission is part of the pathophysiology of levodopa-induced dyskinesias in PD and support further investigation into the role of opioid agents in the management of these involuntary movements.

Adult↗
PubMed1997

Cerebral glucose metabolism in corticobasal degeneration: comparison with progressive supranuclear palsy and normal controls.

The regional metabolic rate of glucose was estimated using 18F-labeled 2-deoxyglucose and positron-emission tomography (PET) in eight patients with corticobasal degeneration (CBD). Measures of cerebral glucose metabolism in these patients were compared with those for nine age-matched normal controls and eight patients with progressive supranuclear palsy (PSP). Compared with that in the normal controls, the CBD patients showed significantly reduced cerebral glucose metabolism in the contralateral hemisphere to the clinically most affected side in the dorsolateral frontal, medial frontal, inferior parietal, sensorimotor, and lateral temporal cortex, as well as in the corpus striatum and the thalamus. In comparison with that in PSP, in CBD the glucose metabolism in the contralateral hemisphere was significantly decreased in the inferior parietal, sensorimotor, lateral temporal cortex, and the corpus striatum. These results confirm the marked asymmetric cerebral involvement in CBD and suggest that there are significant differences between CBD and PSP in the cerebral metabolism in some cerebral regions such as the inferior parietal cortex and sensorimotor cortex, which might reflect the differences in their clinical characteristics.

Aged↗
PubMed1997

Parkinsonism associated with acute intracranial hematomas: an [18F]dopa positron-emission tomography study.

We present the case of a 36-year-old woman with a right temporal hematoma and an overlying subdural hematoma following rupture of a right middle cerebral artery aneurysm. Three weeks after recovering consciousness, she developed a levodopa-responsive parkinsonian syndrome involving the right limbs. A year after the vascular event, she reported subjective improvement in her parkinsonism, which has remained stable since. 18F-dopa positron-emission tomography showed a marked reduction of uptake in the left putamen, raising the possibility that the intracranial hemorrhage unmasked latent Parkinson's disease. To the best of our knowledge, this is the first case of parkinsonism associated with spontaneous acute intracerebral and subdural hematomas.

Acute Disease↗
PubMed1997

PET and the investigation of dementia in the parkinsonian patient.

Parkinsonism and dementia are present in a number of neurodegenerative conditions. They may be a manifestation of isolated brain stem (Parkinson's disease) or diffuse Lewy body disease (DLBD), or be secondary to combined Lewy body and Alzheimer's disease (AD) pathologies. Positron emission tomography (PET) studies show a resting pattern of fronto-temporo-parietal hypometabolism in both, AD and in parkinsonism-dementia (PD-dementia) patients, even when only isolated brain stem Lewy body disease is found at pathology. We have studied three patients fulfilling clinical criteria for diagnosis of DLBD. Their 18F-fluorodeoxyglucose (FDG) PET results showed an AD pattern of fronto-temporo-parietal hypometabolism, though these patients had only mild cognitive dysfunction. Parkinsonism associated with apraxia is observed in corticobasal degeneration (CBD) while impairment of frontal functions, such as planning and sorting, is seen in patients with progressive supranuclear palsy (PSP). PET studies in CBD patients have shown an asymmetric hypometabolism of cortex and thalamus contralateral to the affected limbs, while in PSP patients there is a global metabolic reduction most pronounced in frontal areas and the basal ganglia. These results suggest that metabolic PET studies can help to distinguish PD-dementia, PSP and CBD, but are unable to distinguish PD-dementia from AD. Further studies with post-mortem confirmation are required to establish if DLBD is associated with a distinctive pattern of resting hypometabolism.

Aged↗
PubMed1997

The effects of donor stage on the survival and function of embryonic striatal grafts in the adult rat brain. II. Correlation between positron emission tomography and reaching behaviour.

Grafts of embryonic striatal primordia are able to elicit behavioural recovery in rats which have received an excitotoxic lesion to the striatum, and it is believed that the P zones or striatal-like tissue within the transplants play a crucial role in these functional effects. We performed this study to compare the effects of different donor stage of embryonic tissue on both the morphology (see accompanying paper) and function of striatal transplants. Both the medial and lateral ganglionic eminence was dissected from rat embryos of either 10 mm, 15 mm, 19 mm, or 23 mm crown-rump length, and implanted as a cell suspension into adult rats which had received an ibotenic acid lesion 10 days prior to transplantation. After four months the animals were tested on the "staircase task" of skilled forelimb use. At 10-14 months rats from the groups which had received grafts from 10 mm or 15 mm donor embryos were taken for positron emission tomography scanning in a small diameter positron emission tomography scanner, using ligands to the dopamine D1 and D2 receptors, [11C]SCH 23390 and [11C]raclopride, respectively. A lesion-alone group was also scanned with the same ligands for comparison. Animals which had received transplants from the 10 mm donors showed a significant recovery with their contralateral paw on the "staircase test". No other groups showed recovery on this task. Similarly, the animals with grafts from the youngest donors showed a significant increase in D1 and D2 receptor binding when compared to the lesion-alone group. No increase in signal was observed with either ligand in the group which had received grafts from 15 mm donors. Success in paw reaching showed a strong correlation to both the positron emission tomography signal obtained and the P zone volume of the grafts. These results suggest that striatal grafts from younger donors (10 mm CRL) give greater behavioural recovery than grafts prepared from older embryos. This recovery is due to both the increased proportion of striatal-like tissue within the grafts and an increase in functional D1 and D2 dopamine receptors measured by positron emission tomography, i.e. a more extensive integration of the graft with the host brain.

Animals↗
PubMed1997

Regional hippocampal [11C]flumazenil PET in temporal lobe epilepsy with unilateral and bilateral hippocampal sclerosis.

Using statistical parametric mapping and [11C]flumazenil (FMZ) PET we have previously shown reduction of central benzodiazepine receptor (cBZR) binding restricted to the hippocampus in mesial temporal lobe epilepsy due to unilateral hippocampal sclerosis. However, bilateral hippocampal pathology can be present in up to 50% of patients with mesial temporal lobe epilepsy. Additionally, the limited spatial resolution of PET results in a partial volume effect that affects quantitative analysis of cBZRs and such an effect can mask hippocampal dysfunction. We analysed changes in the [11C]FMZ volume of distribution (FMZ-Vd) before and after correction for partial volume effect in six patients with refractory mesial temporal lobe epilepsy and a quantitative MRI diagnosis of bilateral hippocampal sclerosis, which appeared either symmetrical on MRI (bilateral symmetrical hippocampal sclerosis; three patients) or bilateral but asymmetrical (asymmetrical hippocampal sclerosis; three patients), and in nine patients with refractory mesial temporal lobe epilepsy and unilateral hippocampal sclerosis on MRI than was subsequently histologically verified. Fifteen healthy controls were also studied for comparison. Before correction for partial volume effects, significant unilateral reductions of FMZ-Vd were found in one of the three patients with bilateral symmetrical hippocampal sclerosis, in one of the three asymmetrical hippocampal sclerosis patients and in six of the nine unilateral hippocampal sclerosis patients. No significant bilateral reductions of hippocampal FMZ-Vd were detected. After correction for partial volume effect, all three patients with bilateral symmetrical hippocampal sclerosis showed significant bilateral reductions of FMZ-Vd, and these were asymmetrical in two. All three patients with asymmetrical hippocampal sclerosis and all nine patients with unilateral hippocampal sclerosis on MRI showed unilateral reductions of FMZ-Vd concordant with the side of the EEG focus. In addition one of the three patients with asymmetrical hippocampal sclerosis and three of the nine patients with unilateral hippocampal sclerosis showed significant reductions of FMZ-Vd in the hippocampus contralateral to the side of the EEG focus. Absolute quantification of [11C]FMZ-PET, corrected for partial volume effect, within multiple hippocampal volumes of interest was necessary in order to detect bilateral changes of cBZR in mesial temporal lobe epilepsy due to hippocampal sclerosis with optimal sensitivity. This [11C]FMZ-PET approach was able to demonstrate subtle contralateral abnormalities in one-third of patients thought to have unilateral or bilateral asymmetrical hippocampal sclerosis on MRI. Reduction of cBZR binding was consistently over and above loss of hippocampal volume indicating that atrophy is not the sole determinant of cBZR loss in mesial temporal lobe epilepsy.

Adolescent↗
PubMed1997

Cortical grey matter and benzodiazepine receptors in malformations of cortical development. A voxel-based comparison of structural and functional imaging data.

Using [11C]flumazenil-PET and statistical parametric mapping (SPM), we have shown recently that regions of increased and decreased benzodiazepine receptor density may be seen in patients with localization-related epilepsy due to malformations of cortical development. These abnormalities were seen both within and beyond lesions visually apparent on high-resolution MRI. We have also shown, using an interactive anatomical segmentation technique and volume-of-interest measurements, that subtle and unsuspected abnormalities of cortical grey matter volume were found in the same group of patients on high-resolution MRI, beyond the lesions visually apparent. In 10 patients with localization-related epilepsy and malformations of cortical development, we have now applied the automated and objective technique of SPM to the analysis of high-resolution structural MRI. Each individual patient was compared with 16 normal control subjects. We have then simultaneously compared the structural and functional data obtained for each individual patient with normal control high-resolution MRI and [11C]flumazenil-PET image using a novel technique. This comparison allowed the detection of functional abnormalities that were not accounted for by either visible or unsuspected structural abnormalities, in an automated and statistically rigorous manner. Five patients had abnormalities of cortical grey matter volume detected using SPM; only these five patients had been found abnormal using the previous volume-of-interest technique. Six of the 10 patients showed regions of cerebral cortex with disproportionate flumazenil binding compared with local grey matter volume. This included regions not found to have abnormal flumazenil binding on analysis of the PET data alone. Furthermore, regions found to have abnormal binding on examination of the PET data alone were, in some instances, shown to be accounted for by abnormalities of cortical grey matter volume. We conclude that the analysis of ligand PET data should always include a comparison with structural MRI; such comparisons are greatly facilitated by the novel approach described.

Adolescent↗
PubMed1997

A PET study of voluntary movement in schizophrenic patients experiencing passivity phenomena (delusions of alien control).

Schizophrenic patients experiencing passivity phenomena believe their thoughts and actions to be those of external, or alien, entities. We wished to test the hypothesis that voluntary motor action in such patients would be associated with aberrant patterns of activation within the cerebral motor system. We used H2(15)O PET to study patients while they performed paced joystick movements on two occasions 4-6 weeks apart. During the first scan passivity symptoms were maximal, while by the second scan these symptoms had significantly improved in five of the seven patients. Two control groups were also scanned on two occasions: deluded schizophrenic patients without passivity phenomena and normal subjects. In normal subjects, performance of freely selected joystick movements with the right hand, compared with rest, revealed relative activation of prefrontal, premotor, motor and parietal cortical regions. Schizophrenic patients with passivity showed hyperactivation of parietal and cingulate cortices. This hyperactivation remitted in those subjects in whom passivity decreased over time. This reversible hyperactivity was not a feature of schizophrenics without passivity. Given that these hyperactive cerebral regions subserve attention to internal and external bodily space, and the attribution of significance to sensory information, they provide a plausible anatomical substrate for the misattribution of internally generated acts to external entities: the cardinal feature of delusions of passivity (alien control).

Brain Mapping↗
PubMed1997

Botulinum toxin does not reverse the cortical dysfunction associated with writer's cramp. A PET study.

Previous H2(15)O PET activation studies on patients with idiopathic torsion dystonia (ITD) have shown overactive striatum and frontal accessory areas and underactivity of the primary motor cortex and caudal supplementary motor area (SMA) during volitional movement. We have now examined activation of the motor system in healthy control subjects and patients with writer's cramp while they write a stereotyped word repetitively at a paced rate before and after treatment with botulinum toxin to see if these patients showed a similar pattern of abnormalities and whether they were reversible. As in ITD, our patients with writer's cramp showed impaired activation of the contralateral primary motor cortex, but enhanced activation of frontal association cortex. Botulinum-toxin treatment improved writing and increased activation in parietal cortex and caudal SMA. This may represent either a change in movement strategy or associated cortical reorganization secondary to deefferentation of alpha motor neurons. However, botulinum toxin failed to improve the impaired activation of the primary motor cortex. We conclude that, while botulinum toxin is clinically effective in writer's cramp, it does not reverse the associated dysfunction of primary motor and premotor cortex.

Adult↗
PubMed1997

Evidence for lateral premotor and parietal overactivity in Parkinson's disease during sequential and bimanual movements. A PET study.

Patients with Parkinson's disease have great difficulty in performing sequential and bimanual movements. We used H2(15)O PET to study the regional cerebral blood flow associated with performance of sequential finger movements made unimanually and bimanually in a group of Parkinson's disease patients and a group of control volunteers. In controls, sequential finger movements led to activation of the contralateral motor cortex and inferior parietal cortex (Brodmann area 40), the lateral premotor cortex and bilateral supplementary motor area. No prefrontal activation was seen. Sequential finger movements in the Parkinson's disease group were associated with a similar pattern of activation but there was relative impairment of activation in the mesial frontal and prefrontal areas. A novel finding was the presence of relative overactivity in the lateral premotor and inferolateral parietal regions. We conclude that in Parkinson's disease there is a switch from the use of striato-mesial frontal to parietal-lateral premotor circuits in order to facilitate performance of complex finger movements.

Aged↗
PubMed1997

Pallidotomy in Parkinson's disease increases supplementary motor area and prefrontal activation during performance of volitional movements an H2(15)O PET study.

Supplementary motor area and right dorsal prefrontal cortex activation in Parkinson's disease is selectively impaired during volitional limb movements. Since posteroventral pallidotomy improves motor performance in Parkinson's disease patients 'off' medication (i.e. off medication for 9-12 h), we hypothesized that it would also concomitantly increase supplementary motor area and dorsal prefrontal cortex activation. Six Parkinson's disease patients with a median total motor Unified Parkinson's Disease Rating Scale (UPDRS) of 52.5 (range 34-66) 'off' medication underwent unilateral right posteroventral pallidotomy. The patients had H2(15)O PET when 'off' medication before and 3-4 months after surgery. Each PET study comprised four to six measurements of regional cerebral blood flow either at rest or while performing regularly paced joystick movements in freely selected directions (forward, backward, left or right) using the left hand. Pre- and postoperative scans were performed in an identical manner and the associated levels of activation were compared using statistical parametric mapping. After pallidotomy, the median total motor UPDRS score 'off' medication decreased by 34.7% (P = 0.03) and mean response times of joystick movements following the pacing tones improved by 13.8% (P = 0.08). Relative increases in activation of the supplementary motor area and right dorsal prefrontal cortex were observed during joystick movements (P < 0.001). Decreased activation was seen in the region of the right pallidum (P = 0.001). We conclude that pallidotomy reduces pallidal inhibition of thalamocortical circuits and reverses, at least partially, the impairment of supplementary motor area and dorsal prefrontal cortex activation associated with Parkinson's disease.

Adult↗