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Biomedical subjects

D J Brooks

Publications and source records attributed to D J Brooks.

At least 55 records · Page 3Linked to original sources
PubMed2001

Correlating rates of cerebral atrophy in Parkinson's disease with measures of cognitive decline.

We studied eight clinically non-demented PD patients and ten age-matched controls with serial volumetric T1-weighted MRI. All PD patients underwent full neuropsychological testing at baseline and follow up scans. Sub-voxel coregistration of the serial MRI scans with quantification of changes in total brain substance and ventricular size per year was performed. The PD patients had significant reductions in both percentage and absolute annual brain volume loss when compared to age-matched controls (p < 0.001). There were significant correlations between reductions in percentage brain volume loss and estimated reductions in performance IQ (r = 0.841, p = 0.004) and full scale IQ (r = 0.63, p = 0.049), measured by subtracting IQ measures at time of follow up scan from premorbid estimates. In conclusion, PD patients have a significant rate of median brain volume loss [10.35 (range) 6.69-16.90 ml/year] with no significant loss seen in age-matched controls, and these changes correlate with global measures of cognitive decline. Further longitudinal studies could evaluate whether serial volumetric MRI is a useful technique in predicting the preclinical onset of dementia in Parkinson's disease patients, and its role in the assessment of putative treatments for slowing disease progression.

Aged↗
PubMed2001

Benzodiazepine-GABA(A) receptor binding is very low in dysembryoplastic neuroepithelial tumor: a PET study.

PURPOSE: To determine the nature of abnormalities of gamma-aminobutyric acid (GABA)A-central benzodiazepine (BZD) receptor binding in patients with dysembryoplastic neuroepithelial tumor (DNET) in comparison with normal controls. METHODS: Five patients with DNET and 24 normal controls underwent (11C)flumazenil positron emission tomography (PET) to measure (11C)flumazenil volume of distribution (FMZVD) at the voxel level. Patients were compared with normal controls by using statistical parametric mapping (SPM) and also a partial-volume effect (PVE) corrected volume-of-interest (VOI) analysis covering the entire brain. First, using SPM, the highest Z-score for the entire image representing FMZVD decreases in comparison with the normals was found. Second, regions of abnormal FMZVD were located using SPM, p < 0.001 uncorrected, corrected p < 0.05. Finally, PVE-corrected measures of FMZVD were calculated for each patient VOI and compared wih those of normals, using significance levels of >2.5 standard deviations (SD) for the DNET and >3 SD for all other regions. RESULTS: In all cases, the highest Z-score across the whole image representing decreased FMZVD was within the DNET. In three cases SPM revealed a single region of significantly reduced FMZVD, within the DNET in all three. VOI analysis showed PVE-corrected FMZVD was significantly low in the DNET in four cases. VOI analysis also showed seven other regions of abnormal FMZVD; three were adjacent to a DNET, and two were in mesial temporal areas not affected by DNET. CONCLUSIONS: FMZVD is low in DNET, probably contributing to epileptogenicity.

Adult↗
PubMed2001

The role of the striatum and hippocampus in planning: a PET activation study in Parkinson's disease.

Previous work has identified the prefrontal cortex (PFC) and striatum as participating in the planning and selection of movements. We compared the brain activation patterns during planning in Parkinson's disease patients and age-matched controls using H(2)(15)O-PET and the Tower of London (TOL) task. In this study, our mildly affected Parkinson's disease group performed as well as the control group but showed a different pattern of neuronal activation. In the two groups, overlapping areas of the PFC were activated but, whereas the right caudate nucleus was activated in the control group, this was not evident in the Parkinson's disease patients. This suggests that normal normal frontal lobe activation can occur in Parkinson's disease despite abnormal processing within the basal ganglia. Moreover, right hippocampus activity was suppressed in the controls and enhanced in the Parkinson's disease patients. This could represent a shift to the declarative memory system in Parkinson's disease during performance of the TOL task, possibly resulting from insufficient working memory capacity within the frontostriatal system.

Aged↗
PubMed2001

Central benzodiazepine receptors in malformations of cortical development: A quantitative study.

We calculated [(11)C]flumazenil volume of distribution ([(11)C]FMZ-V(d)) after correction for partial volume effect in 10 patients with malformations of cortical development (MCDs) and partial seizures, to quantify the GABA(A)-central benzodiazepine receptor complex. Abnormal grey matter and adjacent or overlying cortex were outlined individually and added to an individualized anatomical template for correction for partial volume effect. Nine of 10 patients showed single or multiple increases or decreases in [(11)C]FMZ-V(d) in or around MCDs. Two of three patients with band heterotopia showed multiple increases in the overlying cortex. In three of four patients with subependymal nodular heterotopia, nodules had lower [(11)C]FMZ-V(d) than the overlying cortex, which was normal. Decreases in [(11)C]FMZ-V(d) were found in two of three clefts and one of six adjacent regions in one schizencephalic patient; another had normal [(11)C]FMZ-V(d) in the thickened cortex itself but increases in all adjacent regions. Binding was reduced within focal cortical dysplasia but increased in adjacent cortex. [(11)C]FMZ-V(d) was normal within one patient's polymicrogyric cortex but increased in one of six adjacent volumes of interest. The localization of abnormalities correlated with EEG and clinical data in cortical MCDs. Flumazenil binding was decreased in some MCDs with increased grey matter volume and increased in some adjacent or overlying areas of normal-appearing cortex, suggesting functional abnormalities beyond MRI- detectable structural changes.

Adolescent↗
PubMed2001

Updated guidelines for the management of Parkinson's disease.

New data on diagnosis, drug therapy, surgery and psychosocial concerns have emerged since the publication of the 1998 Guidelines for the Management of Parkinson's Disease. This article reviews new data and addresses issues left unanswered in the previous guidelines.

Aged↗
PubMed2000

The effect of the nitric oxide donor glyceryl trinitrate on global and regional cerebral blood flow in man.

Despite their potential use as cerebral vasodilatory agents there are few studies of the effect of nitric oxide (NO) donors on the cerebral circulation in non-anaesthetised man. We determined the effect of the NO donor glyceryl trinitrate (GTN) at clinically relevant doses on global and regional cerebral blood flow (CBF) in healthy non-anaesthetised volunteers, using H(2)(15)O PET, ultrasonic colour velocity flow imaging of carotid artery flow, and transcranial Doppler (TCD) of middle cerebral artery velocities (MCAv). Three rates of GTN infusion (0.1, 0.4, 1.0 microg/kg/min) were used. There was no significant change in common or internal carotid artery flow following GTN administration although a dose dependent fall in MCAv post GTN was observed. There was no significant change in either global or regional CBF following GTN. Thus intravenous GTN at therapeutic doses in awake humans does not alter global or regional CBF. However it does produce basal cerebral artery vasodilatation as evidenced by a fall in MCAv in the absence of a change in internal carotid artery flow.

Adult↗
PubMed2000

A five-year study of the incidence of dyskinesia in patients with early Parkinson's disease who were treated with ropinirole or levodopa.

BACKGROUND: There is debate about whether the initial treatment for patients with Parkinson's disease should be levodopa or a dopamine agonist. METHODS: In this prospective, randomized, double-blind study, we compared the safety and efficacy of the dopamine D2-receptor agonist ropinirole with that of levodopa over a period of five years in 268 patients with early Parkinson's disease. If symptoms were not adequately controlled by the assigned study medication, patients could receive supplementary levodopa, administered in an open-label fashion. The primary outcome measure was the occurrence of dyskinesia. RESULTS: Eighty-five of the 179 patients in the ropinirole group (47 percent) and 45 of the 89 patients in the levodopa group (51 percent) completed all five years of the study. In the ropinirole group 29 of the 85 patients (34 percent) received no levodopa supplementation. The analysis of the time to dyskinesia showed a significant difference in favor of ropinirole (hazard ratio for remaining free of dyskinesia, 2.82; 95 percent confidence interval, 1.78 to 4.44; P<0.001). At five years, the cumulative incidence of dyskinesia (excluding the three patients who had dyskinesia at base line), regardless of levodopa supplementation, was 20 percent (36 of 177 patients) in the ropinirole group and 45 percent (40 of 88 patients) in the levodopa group. There was no significant difference between the two groups in the mean change in scores for activities of daily living among those who completed the study. Adverse events led to the early withdrawal from the study of 48 of 179 patients in the ropinirole group (27 percent) and 29 of 89 patients in the levodopa group (33 percent). The mean (+/-SD) daily doses given by the end of the study were 16.5+/-6.6 mg of ropinirole (plus 427+/-221 mg of levodopa in patients who received supplementation) and 753+/-398 mg of levodopa (including supplements). CONCLUSIONS: Early Parkinson's disease can be managed successfully for up to five years with a reduced risk of dyskinesia by initiating treatment with ropinirole alone and supplementing it with levodopa if necessary.

Aged↗
PubMed2000

11C-flumazenil PET in patients with refractory temporal lobe epilepsy and normal MRI.

BACKGROUND: Using 11C-flumazenil (FMZ) PET with correction for partial-volume effect, reductions of central benzodiazepine receptor (cBZR) binding can be detected reliably in vivo on remaining neurons in sclerotic hippocampi of patients with mesial temporal lobe epilepsy (TLE). OBJECTIVE: To delineate abnormalities of 11C-FMZ binding in patients with medically refractory TLE and normal quantitative MRI. METHODS: Analysis of parametric images of FMZ volume of distribution (Vd) using two complementary approaches: 1) MRI-based volume of interest (VOI) approach with partial volume effect correction for multiple hippocampal and extrahippocampal VOIs; and 2) statistical parametric mapping (SPM) to localize significant 11C-FMZ binding changes objectively on a voxel-by-voxel basis. RESULTS: Significant abnormalities of absolute FMZ-Vd were found after partial volume effect correction in 5 of 10 patients: unilateral decrease in the amygdala ipsilateral to the EEG focus (1), unilateral hippocampal decreases and bilateral temporal and extratemporal neocortical decreases (2), unilateral increase in the temporal neocortex together with extratemporal neocortical increases (1), and bilateral posterior hippocampal increases together with temporal neocortical increases (1). In the three patients with extratemporal neocortical changes, the concomitant unilateral hippocampal or temporal neocortical changes were contralateral to the presumed epileptic focus. Significant asymmetries of FMZ-Vd between homologous regions were found in six patients. In four of those patients, absolute FMZ-Vd for the homologous regions were within normal limits, with two of the four patients showing relatively higher hippocampal values ipsilateral to the presumed epileptic focus. SPM analysis localized significant abnormalities of FMZ-Vd in similar locations in three of the seven patients in whom VOI analysis detected significant changes. In addition, SPM indicated significant unilateral contralateral hippocampal decreases in an eighth patient. However, both methods failed to localize epileptic foci in two patients identified by depth-EEG recordings. CONCLUSIONS: 11C-FMZ PET showed focal increases as well as decreases of FMZ binding in 80% of patients with refractory TLE and normal high-quality MRI but was not consistently helpful in localizing the epileptic foci.

Adult↗
PubMed2000

Atypical parkinsonism in Afro-Caribbean and Indian origin immigrants to the UK.

This article reviews evidence for the occurrence of atypical parkinsonism in Afro-Caribbean and Indian ethnic minority subjects living in western countries, particularly the UK. Current information on the frequency, pattern, and prevalence of Parkinson's disease and parkinsonism in these communities is unclear and controversial. While several workers have suggested that there is a low prevalence of Parkinson's disease in populations of African origin, other workers have suggested a higher prevalence of Parkinson's disease in African Americans. Furthermore, little information is available in relation to the pattern of parkinsonism in these subjects. A recent phenomenologic study of parkinsonism in the French West Indies by Caparros-Lefebvre and colleagues has indicated a significantly increased frequency of atypical parkinsonism in local non-white subjects. Since 1995, we have been studying the pattern and frequency of parkinsonism in Afro-Caribbean and Indian (originating from the Indian subcontinent) patients living in the UK, with London serving as the coordinating center. Our results indicate that there is a three- to fourfold increase in the frequency of occurrence of sporadic atypical parkinsonism characterized by levodopa hyporesponsiveness, bradykinesia-dominant disease, and early cognitive dysfunction in these patients even after exclusion of patients with clinically probable multiple system atrophy, progressive supranuclear palsy, and Lewy body dementia. These findings are similar to observations made in the French West Indies. Ongoing studies in India suggest that atypical parkinsonism also affects local patients, and the pattern of parkinsonism tends to differ from Afro-Caribbean subjects in the UK. Studies are currently underway to unravel the mechanism of increased frequency of atypical parkinsonism in these ethnic groups and include genetic studies addressing polymorphisms of enzymes metabolizing levodopa, dietary neurotoxin screen and functional imaging studies of the striatum using positron emission tomography. Furthermore, the contribution of diabetes mellitus and hypertension, commonly seen in these ethnic groups, is also being examined.

Black People↗
PubMed2000

Health-related quality of life following bilateral intrastriatal transplantation in Parkinson's disease.

Intrastriatal transplantation of embryonic dopaminergic tissue is a new, experimental approach for the treatment of Parkinson's disease (PD). Clinical trials have shown longterm graft survival and therapeutically valuable improvements with decreased L-dopa dose and time spent in the "off"-phase, and reduced rigidity and hypokinesia. We have measured health-related quality of life (HRQoL) using the Nottingham Health Profile (NHP) in five patients subjected to bilateral transplantation in the caudate and putamen to explore the influence of intrastriatal grafts on HRQoL and the value of such measures in trials of restorative therapies. The results demonstrate improved HRQoL following transplantation, with individual patients showing striking improvements within different dimensions of the NHP as well as the NHP distress index (NHPD). The most pronounced improvements after grafting were observed for physical mobility along with emotional reactions and energy. These results indicate that intrastriatal transplantation of embryonic dopaminergic tissue can give rise to improvements within most areas of HRQoL, and that HRQoL measurements provide important information additional to that obtained by traditional, symptom-oriented assessment protocols. However, the optimal approach to HRQoL measurement in PD remains to be determined.

Activities of Daily Living↗
PubMed2000

Monitoring neuroprotection and restorative therapies in Parkinson's disease with PET.

In this article the role of functional imaging (PET and SPECT) as a surrogate marker for following the progression of Parkinson's disease (PD) is discussed. The potential value of PET and SPECT for assessing the efficacy of putative neuroprotective agents in PD is considered and a review of 18F-dopa PET findings in transplantation trials involving implantation of human and procine fetal mesencephalic tissue is presented. It is concluded that functional imaging provides a valuable adjunct to clinical assessment when judging the efficacy of neuroprotective and restorative approaches to PD.

Antiparkinson Agents↗
PubMed2000

Morphological and functional imaging studies on the diagnosis and progression of Parkinson's disease.

This paper reviews the relative abilities of magnetic resonance imaging (MRI), positron emission tomography (PET), single photon emission tomography (SPECT), and proton magnetic resonance spectroscopy (MRS) to detect Parkinson's disease and monitor its progression. Currently, the main role of MRI lies in its ability to discriminate atypical syndromes from Parkinson's disease; however, new volumetric approaches may soon allow progression of nigral degeneration to be followed. Proton MRS can also detect reduced levels of putamen N-acetyl aspartate (NAA) in many patients with atypical parkinsonian syndromes. PET and SPECT are both sensitive means of detecting the presence of impaired dopamine terminal function in the striatum and following its progression. PET currently has the greater spatial resolution and provides the added advantages that it also allows extra-striatal dopaminergic function to be monitored.

Disease Progression↗
PubMed2000

Long-term changes of GABAergic function in the sensorimotor cortex of amputees. A combined magnetic stimulation and 11C-flumazenil PET study.

Primary sensory and motor areas of the cerebral cortex contain organised maps of the body. These maps appear to reorganise after damage to the peripheral parts of the sensory or motor systems, so that the cortical representation of undamaged structures expands at the expense of the damaged parts. Several studies in animals have suggested that decreased activity of the inhibitory GABAergic neurones is responsible for driving these changes. However, whether similar mechanisms sustain the effects in the longer term in humans is unknown. The present study addressed this question by examining reorganisation of sensorimotor areas of cortex in six unilateral upper limb amputees several years after the initial injury. We measured two independent indices of GABAergic function. Volumes of distribution of GABA(A) receptors were determined from 11C-flumazenil binding measured with positron emission tomography (PET). The strength of inhibition in the motor cortex was measured with paired-pulse transcranial magnetic stimulation. In the six amputees taken as a whole and compared with 24 normal subjects, there was a highly significant increase in 11C-flumazenil binding in the upper limb region of primary sensorimotor cortex bilaterally and in medial frontal cortex of the hemisphere contralateral to the amputation. Surprisingly, however, there was no change in the time course or strength of intra-cortical inhibition in the motor cortex of the amputees compared with matched control subjects. The increased 11C-flumazenil binding may reflect up-regulation of GABA(A) receptors to compensate for a decrease in the GABA content or activity of inhibitory neurones. Up-regulation of GABA(A) receptors may also indicate that long-term changes require stabilisation of cortical organisation.

Adult↗
PubMed2000

PET studies and motor complications in Parkinson's disease.

Parkinson's disease (PD) patients with motor complications show a greater reduction in putamen [18F]dopa uptake on positron emission tomography (PET) compared with sustained responders to L-dopa, although individual ranges overlap considerably. This implies that, although loss of putamen dopamine storage predisposes motor complications in PD, it cannot be the only factor determining timing of onset. Additional PET studies suggest that loss of striatal dopamine storage capacity along with pulsatile exposure to exogenous L-dopa results in pathologically raised synaptic dopamine levels and deranged basal ganglia opioid transmission.This, rather than altered dopamine receptor binding, then causes inappropriate overactivity of basal ganglia-frontal projections, resulting in breakthrough involuntary movements.

Antiparkinson Agents↗
PubMed2000

Imaging basal ganglia function.

In this review, the value of functional imaging for providing insight into the role of the basal ganglia in motor control is reviewed. Brain activation findings in normal subjects and Parkinson's disease patients are examined and evidence supporting the existence for functionally independent distributed basal ganglia-frontal loops is presented. It is argued that the basal ganglia probably act to focus and filter cortical output, optimising the running of motor programs.

Basal Ganglia↗