Biomedical subjects

Guy B Williams

Publications and source records attributed to Guy B Williams.

7 recordsLinked to original sources

PubMed2007

Hyperventilation following head injury: effect on ischemic burden and cerebral oxidative metabolism.

OBJECTIVE: To determine whether hyperventilation exacerbates cerebral ischemia and compromises oxygen metabolism (CMRO2) following closed head injury. DESIGN: A prospective interventional study. SETTING: A specialist neurocritical care unit. PATIENTS: Ten healthy volunteers and 30 patients within 10 days of closed head injury. INTERVENTIONS: Subjects underwent oxygen-15 positron emission tomography imaging of cerebral blood flow, cerebral blood volume, CMRO2, and oxygen extraction fraction. In patients, positron emission tomography studies, somatosensory evoked potentials, and jugular venous saturation (SjO2) measurements were obtained at Paco2 levels of 36+/-3 and 29+/-2 torr. MEASUREMENTS AND MAIN RESULTS: We estimated the volume of ischemic brain and examined the efficiency of coupling between oxygen delivery and utilization using the sd of the oxygen extraction fraction distribution. We correlated CMRO2 to cerebral electrophysiology and examined the effects of hyperventilation on the amplitude of the cortical somatosensory evoked potential response. Patients showed higher ischemic brain volume than controls (17+/-22 vs. 2+/-3 mL; p<or=.05), with worse matching of oxygen delivery to demand (p<.001). Hyperventilation consistently reduced cerebral blood flow (p<.001) and resulted in increases in oxygen extraction fraction and ischemic brain volume (17+/-22 vs. 88+/-66 mL; p<.0001), which were undetected by SjO2 monitoring. Mean CMRO2 was slightly increased following hyperventilation, but responses were extremely variable, with 28% of patients demonstrating a decrease in CMRO2 that exceeded 95% prediction intervals for zero change in one or more regions. CMRO2 correlated with cerebral electrophysiology, and cortical somatosensory evoked potential amplitudes were significantly increased by hyperventilation. CONCLUSIONS: The acute cerebral blood flow reduction and increase in CMRO2 secondary to hyperventilation represent physiologic challenges to the traumatized brain. These challenges exhaust physiologic reserves in a proportion of brain regions in many subjects and compromise oxidative metabolism. Such ischemia is underestimated by common bedside monitoring tools and may represent a significant mechanism of avoidable neuronal injury following head trauma.

Adolescent↗

PubMed2004

Neural correlates of semantic and behavioural deficits in frontotemporal dementia.

Patients with frontotemporal dementia (FTD) can present with the clinical syndrome of semantic dementia due to a progressive loss of semantic knowledge or a neuropsychiatric syndrome characterised by aberrant social behaviours although frequently both co-exist. It has been assumed that the former is underpinned by damage to the temporal lobes and the latter, predominantly, by damage to the frontal lobes. Using the technique of voxel-based morphometry, we studied a group of FTD cases (n = 18) with a range of cognitive and neuropsychiatric features to correlate loss of semantic knowledge (as measured by the sum of two semantic tests) and aberrant behaviour (as measured by the neuropsychiatric inventory, NPI) with regional loss of grey matter volume. Semantic breakdown correlated with extensive loss of grey matter volume throughout the left anterior temporal lobe and less significantly with right temporal pole and subcallosal gyrus. Aberrant behaviour correlated with loss of grey matter volume in the dorso-mesial frontal lobe--paracingulate region, Brodmann areas 6/8/9--more so on the right. The frontal paracingulate correlation suggests that damage to this region may significantly contribute to the genesis of the behavioural syndrome seen in FTD.

Aged↗

PubMed2004

Does induced hypertension reduce cerebral ischaemia within the traumatized human brain?

Recent changes in published guidelines for the management of patients with severe head injury are based on data showing that aggressive maintenance of cerebral perfusion pressure (CPP) can worsen outcome due to extracranial complications of therapy. However, it remains unclear whether CPP augmentation could reduce cerebral ischaemia, a finding which might prompt the search for CPP augmentation protocols that avoid these extracranial complications. We studied 10 healthy volunteers and 20 patients within 6 days of closed head injury. All subjects underwent imaging of cerebral blood flow (CBF), blood volume (CBV), oxygen metabolism (CMRO2) and oxygen extraction fraction (OEF) using 15O PET. In addition, for patients, the EEG power ratio index (PRI), burst suppression ratio and somatosensory evoked potentials (SEP) were obtained and CPP was increased from 68 +/- 4 to 90 +/- 4 mmHg using an infusion of norepinephrine and measurements were repeated. Following elevation of CPP, CBF and CBV were increased and CMRO2 and OEF were reduced (P < 0.001 for all comparisons). Regions with a reduction in CMRO2 were associated with the greatest reduction in OEF (r2 = 0.3; P < 0.0001). Although CPP elevation produced a significant fall in the ischaemic brain volume (IBV) (from 15 +/- 16 to 5 +/- 4 ml; P < 0.01) and improved flow metabolism coupling, the IBV was small and clinically insignificant in the majority of these patients. However, the reduction in IBV was directly related to the baseline IBV (r2 = 0.97; P < 0.001) and patients with large baseline IBV showed substantial and clinically significant reductions. CPP augmentation increased the EEG PRI (5.0 +/- 1.5 versus 4.3 +/- 1.4, P < 0.01), implying an overall decrease in neural activity, but these changes did not correlate with the reduction in CMRO2 and there was no change in SEP cortical amplitude (N20-P27). These data provide support for recent changes in recommended CPP levels for head injury management across populations of patients with significant head injury. However, they do not provide guidance on whether the intervention may be more appropriate at earlier stages after injury, or in patients selected because of high baseline IBV. It also remains unclear whether CPP values below 65 mmHg can be safely used in this population. Clarification of the significance of a reduction in CMRO2 and neuronal electrical function will require further study.

Adolescent↗

PubMed2004

Pseudo-neglect in Huntington's disease correlates with decreased angular gyrus density.

Visuospatial attentional bias was examined in Huntington's disease (HD) patients with mild disease, asymptomatic gene-positive patients and controls. No group differences were found on the grey scales task (which is a non-motor task of visuospatial attentional bias), although patients' trinucleotide (CAG) repeat length correlated with increasing leftward bias. On the line bisection task, symptomatic patients made significantly larger leftward bisection errors relative to controls, who showed the normal slight degree of leftward error (pseudo-neglect). The asymptomatic group showed a trend for greater leftward error than controls. A subset of participants went on to have structural MRI, which showed a correlation between increased leftward error on the line bisection task and reduced density in the angular gyrus area (BA39) bilaterally. This finding is consistent with recent literature suggesting a critical role for the angular gyrus in the lateralization of visuospatial attention.

Adult↗

PubMed2004

Incidence and mechanisms of cerebral ischemia in early clinical head injury.

Antemortem demonstration of ischemia has proved elusive in head injury because regional CBF reductions may represent hypoperfusion appropriately coupled to hypometabolism. Fifteen patients underwent positron emission tomography within 24 hours of head injury to map cerebral blood flow (CBF), cerebral oxygen metabolism (CMRO2), and oxygen extraction fraction (OEF). We estimated the volume of ischemic brain (IBV) and used the standard deviation of the OEF distribution to estimate the efficiency of coupling between CBF and CMRO2. The IBV in patients was significantly higher than controls (67 +/- 69 vs. 2 +/- 3 mL; P < 0.01). The coexistence of relative ischemia and hyperemia in some patients implies mismatching of perfusion to oxygen use. Whereas the saturation of jugular bulb blood (SjO2) correlated with the IBV (r = 0.8, P < 0.01), SjO2 values of 50% were only achieved at an IBV of 170 +/- 63 mL (mean +/- 95% CI), which equates to 13 +/- 5% of the brain. Increases in IBV correlated with a poor Glasgow Outcome Score 6 months after injury (rho = -0.6, P < 0.05). These results suggest significant ischemia within the first day after head injury. The ischemic burden represented by this "traumatic penumbra" is poorly detected by bedside clinical monitors and has significant associations with outcome.

Adolescent↗

PubMed2004

The human perirhinal cortex and semantic memory.

Studies in macaque monkeys indicate that the perirhinal cortex in the temporal lobe participates in object memory. This function may be analogous to aspects of human semantic memory (knowledge of objects, concepts, faces and words). To date, the status of perirhinal cortex has not specifically been investigated in patients with semantic deficits as seen in semantic dementia, the temporal lobe variant of frontotemporal dementia. High-resolution three-dimensional magnetic resonance imaging was performed in subjects with semantic dementia and Alzheimer's disease (characterized in its early stages by selective episodic memory impairment) and in healthy age-matched controls. Hippocampal, perirhinal, temporopolar and entorhinal cortex volumes were measured by outlining areas on successive scan slices according to recognized landmarks. The entorhinal and hippocampal regions were further subdivided into anterior and posterior parts. In keeping with the hypothesized contribution of the perirhinal cortex to semantic memory function, we found greater involvement of this region, together with the temporopolar and anterior entorhinal cortices, in semantic dementia than in either Alzheimer's disease patients or control subjects. Performance on a range of semantic tests also correlated with perirhinal volume. Bilateral reduction in hippocampal volume compared with controls was seen in Alzheimer's disease. In conclusion, atrophy of the human perirhinal cortex, and of directly connected areas, was associated with semantic memory impairment but not episodic memory impairment, as predicted from the primate work.

Aged↗

PubMed2003

Progressive non-fluent aphasia is associated with hypometabolism centred on the left anterior insula.

Progressive non-fluent aphasia (PNFA) is a syndrome in which patients lose the ability to communicate fluently in the context of relative preservation of single word comprehension and non-linguistic cognitive abilities. Neuroimaging in case studies with PNFA has failed to identify a consistent neural substrate for the language disorder. In this study of a group of patients (n=10) whose presenting complaint was progressive dysfluency, resting cerebral metabolism was measured using [18F]fluorodeoxyglucose-PET and analysed with the technique of statistical parametric mapping (SPM). Regional atrophy was assessed with voxel-based morphometry (VBM). Seven patients had a 'pure' PNFA syndrome, while the remaining three had additional features of a more pervasive dementia. Compared with controls, the patients showed hypometabolism in several regions that, most notably, included the left anterior insula/frontal opercular region. The VBM analysis revealed only one small area of atrophy in the left peri-Sylvian region. Analysis of the pure PNFA cases (n=7) relative to controls yielded qualitatively similar results to those of the whole group, suggesting that these cases were also at risk of a more generalized dementia, a finding borne out in subsequent follow-up of two cases to date. The PNFA group was then compared with a group with Alzheimer's disease (n=10) whose clinical profile did not include non-fluent aphasic features. In this analysis, the only persisting hypometabolic region was that centred over the left anterior insula. VBM did not identify any regional differences in atrophy between PNFA and Alzheimer's disease. In the light of current theories of fluent language production, the findings offer anatomical evidence that the breakdown in fluency is due to a motor articulatory planning deficit (speech apraxia) combined with a variable degree of agrammatism.

Aged↗