PubMed Health⌕ Search

Biomedical subjects

E A Warburton

Publications and source records attributed to E A Warburton.

At least 19 recordsLinked to original sources

How affected is oxygen metabolism in DWI lesions?: A combined acute stroke PET-MR study.

OBJECTIVE: To use back-to-back diffusion-weighted imaging (DWI) and PET to obtain quantitative measures of the cerebral metabolic rate of oxygen (CMRO(2)) within DWI lesions, and to assess the perfusion-metabolism coupling status by measuring the cerebral blood flow and the oxygen extraction fraction within DWI lesions. METHODS: Six prospectively recruited acute carotid-territory stroke patients completed the imaging protocol, which was commenced 7 to 21 hours from onset and combined DWI derived from state-of-the-art diffusion tensor imaging sequencing using a 3-T magnet and fully quantitative (15)O-PET. The PET variables were obtained in individual DWI lesions in each patient. RESULTS: Across patients, the CMRO(2) was reduced in the DWI lesion relative to mirror (mean reduction 39.5%; p = 0.028). Examining individual DWI lesions, however, revealed considerable variability in the extent of this CMRO(2) reduction. The flow-metabolism coupling pattern underlying the DWI lesion was also variable, including ongoing ischemia, mild oligemia, and partial or complete reperfusion. DISCUSSION: Diffusion-weighted imaging (DWI) lesions generally reflect substantial disruption of energy metabolism. However, the degree of metabolic disruption is variable, indicating DWI lesions may not always represent irreversibly damaged tissue. Finally, because DWI lesions can persist despite reperfusion, assessment of perfusion is necessary for interpretation of DWI changes in acute stroke.

Aged↗

Perfusion CT helps decision making for thrombolysis when there is no clear time of onset.

Current guidelines on thrombolysis post stroke with recombinant tissue plasminogen activator (rt-PA) exclude its use where time of onset is unknown, thus denying some patients potentially beneficial treatment. Contrast enhanced perfusion computed tomography (pCT) imaging can be used together with plain CT and information on clinical deficits to decide whether or not thrombolysis should be initiated even though the exact time of stroke onset is unknown. Based on the results of pCT and CT, rt-PA was administered to two patients with unknown time of stroke onset; one of the patients also underwent suction thrombectomy. Results in both cases were excellent.

Aged↗

Quantification of index tapping regularity after stroke with tri-axial accelerometry.

OBJECTIVE: Quantifying intrinsic components of movement may help to better understand the nature of motor deficits after stroke. Here we quantify the ability of stroke patients to finger tap in rhythm with auditory cues given at physiological rate. METHODS: Using tri-axial accelerometry, we measured tapping regularity (Regularity Index) during auditory-cued index-to-thumb tapping at 1.25 Hz in 20 prospectively selected right-handed chronic stroke patients (mean age 61 yrs) and 20 right-handed healthy subjects (7 young and 13 age matched; mean age 24 and 58 yrs, respectively). With the aim to validate our method, two measures of clinical deficit, the European Stroke Scale (ESS) and the maximum number of index-thumb taps in 15s (IT-Max) were recorded on the same day. RESULTS: There was no effect of age or hand used on the Regularity Index in the control subjects. In patients, the Regularity Index of their affected hand was significantly worse compared to their unaffected hand and to age-matched controls (p<0.05 and p<0.01, respectively). The Regularity Index significantly correlated with the ESS and IT-Max in the clinically expected direction (p=0.025 and 0.001, respectively). CONCLUSION: These data indicate that our method has validity to quantify finger-tapping regularity. After stroke, there is a deficit in the ability to keep pace with auditory cues that correlates, but does not equate, with other indices of motor function. Quantifying tapping regularity may provide novel insights into the mechanisms underlying recovery of finger dexterity after stroke.

Acoustic Stimulation↗

Lone atrial septal aneurysm and stroke--a case report and review of the literature.

The aetiology of stroke in young patients is usually difficult to establish. Despite extensive investigations, the cause of stroke remains unknown in a large percentage of these patients. We report a case of stroke in a young patient in whom the only associated aetiological factor was a lone atrial septal aneurysm. We discuss the investigational tools in the diagnosis of atrial septal aneurysms and study the aetiopathogenesis of strokes and the risk of recurrent strokes associated with their presence. We also review the evidence for the presently available therapies for prevention of further strokes in such patients.

Journal Article↗

Utility of an ultrafast magnetic resonance imaging protocol in recent and semi-recent strokes.

OBJECTIVE: To evaluate the technical feasibility of an integrated ultrafast head magnetic resonance (MR) protocol using a sensitivity encoding (SENSE) technique for depicting parenchymal ischaemia and vascular compromise in patients with suspected recent stroke. METHODS: 23 patients were evaluated with the ultrafast MR protocol using T2, T1, fluid attenuated inversion recovery (FLAIR), 3D time of flight magnetic resonance angiography (MRA), and diffusion weighted imaging (DWI) sequences. These were compared with routine conventional MR sequences. RESULTS: One patient could not tolerate conventional imaging, although imaging using the three minute head SENSE protocol was diagnostic. Both conventional and ultrafast protocols were of similar diagnostic yield in the remaining patients. There were no significant differences in clinical diagnostic quality for the T1, T2, FLAIR, and DWI sequences. One MRA examination was of better quality when SENSE was used, owing to reduced motion artefacts and shorter imaging time. CONCLUSIONS: It is possible to undertake a comprehensive MR examination in stroke patients in approximately three to five minutes. Ultrafast imaging may become a useful triage tool before thrombolytic therapy. It may be of particular benefit in patients unable to tolerate longer sequences. Further work is necessary to confirm these findings in hyperacute stroke.

Adult↗

Cerebral neutrophil recruitment, histology, and outcome in acute ischemic stroke: an imaging-based study.

BACKGROUND AND PURPOSE: Evidence now exists for a pathogenic role for neutrophils in acute cerebral ischemia. We have studied the patterns and temporal profile of cerebral neutrophil recruitment to areas of acute ischemic stroke (IS) and have attempted to correlate this with neurological status and outcome. METHODS: Patients with cortical middle cerebral artery (MCA) IS were recruited within 24 hours of clinical onset. Neutrophil recruitment was studied using indium-111 (111In) troponolate-labeled neutrophils, planar imaging, and single-photon emission computed tomography (SPECT). Volume of brain infarction was calculated from concurrent computed tomography (CT). Hematoxylin and eosin sections were obtained postmortem (n=2). Outcome was measured using Barthel, Rankin, and National Institute of Health Stroke (NIHSS) scales. RESULTS: Fifteen patients were studied. Significant 111In-neutrophil recruitment to ipsilateral hemisphere, as measured by asymmetry index (AI), was demonstrated within 24 hours of onset in 9 patients; this response was heterogenous between patients and on repeated measurement attenuated over time. Histologically, recruitment was confirmed within intravascular, intramural, and intraparenchymal compartments. Interindividual heterogeneity in neutrophil response did not correlate with infarct volume or outcome. In an exploratory analysis, neutrophil accumulation appeared to correlate significantly with infarct expansion (Spearman rho=0.66; P=0.03, n=12). CONCLUSIONS: Neutrophils recruit to areas of ischemic brain within 24 hours of symptom onset. This recruitment attenuates over time and is confirmed histologically. While neutrophil accumulation may be associated with either the magnitude or the rate of infarct growth, these results require confirmation in future studies.

Brain Ischemia↗

Contrast-enhanced MR angiography for carotid disease: diagnostic and potential clinical impact.

OBJECTIVE: To compare contrast-enhanced MR angiography (CEMRA) with intra-arterial digital subtraction angiography (DSA) for evaluating carotid stenosis. METHODS: A total of 167 consecutive symptomatic patients, scheduled for DSA following screening duplex ultrasound (DUS), were prospectively recruited to have CEMRA. Three independent readers reported on each examination in a blinded and random manner. Agreement was assessed using the Bland-Altman method. Diagnostic and potential clinical impact of CEMRA was evaluated, singly and in combination with DUS. RESULTS: CEMRA tended to overestimate stenosis by a mean bias ranging from 2.4 to 3.8%. A significant part of the disagreement between CEMRA and DSA was directly caused by interobserver variability. For detection of severe stenosis, CEMRA alone had a sensitivity of 93.0% and specificity of 80.6%, with a diagnostic misclassification rate of 15.0% (n = 30). More importantly, clinical decision-making would, however, have been potentially altered only in 6.0% of cases (n = 12). The combination of concordant DUS and CEMRA reduced diagnostic misclassification rate to 10.1% (n = 19) at the expense of 47 (24.9%) discordant cases needing to proceed to DSA. An intermediate approach of selective DUS review resulted in a marginally worse diagnostic misclassification rate of 11.6% (n = 22) but with only 6.8% of discordant cases (n = 13). CONCLUSIONS: DSA remains the gold standard for carotid imaging. The clinical misclassification rate with CEMRA, however, is acceptably low to support its safe use instead of DSA. The appropriateness of combination strategies depends on institutional choice and cost-effectiveness issues.

Aged↗

Human cellular inflammation in the pathology of acute cerebral ischaemia.

Leucocytes form important effector pathways for inflammation. This article reviews the clinical evidence for the presence of a cellular inflammatory response in cerebral ischaemia, and attempts to define its temporal profile and spatial distribution. The processes involved in recruitment and activation of leucocytes in this context are addressed, and the successes and failures of interventions aimed at these processes discussed.

Acute Disease↗

Imaging atherosclerotic plaque inflammation with [18F]-fluorodeoxyglucose positron emission tomography.

BACKGROUND: Atherosclerotic plaque rupture is usually a consequence of inflammatory cell activity within the plaque. Current imaging techniques provide anatomic data but no indication of plaque inflammation. The glucose analogue [18F]-fluorodeoxyglucose (18FDG) can be used to image inflammatory cell activity non-invasively by PET. In this study we tested whether 18FDG-PET imaging can identify inflammation within carotid artery atherosclerotic plaques. METHODS AND RESULTS: Eight patients with symptomatic carotid atherosclerosis were imaged using 18FDG-PET and co-registered CT. Symptomatic carotid plaques were visible in 18FDG-PET images acquired 3 hours post-18FDG injection. The estimated net 18FDG accumulation rate (plaque/integral plasma) in symptomatic lesions was 27% higher than in contralateral asymptomatic lesions. There was no measurable 18FDG uptake into normal carotid arteries. Autoradiography of excised plaques confirmed accumulation of deoxyglucose in macrophage-rich areas of the plaque. CONCLUSIONS: This study demonstrates that atherosclerotic plaque inflammation can be imaged with 18FDG-PET, and that symptomatic, unstable plaques accumulate more 18FDG than asymptomatic lesions.

Aged↗

Dynamic diaschisis: anatomically remote and context-sensitive human brain lesions.

Functional neuroimaging was used to investigate how lesions to the Broca's area impair neuronal responses in remote undamaged cortical regions. Four patients with speech output problems, but relatively preserved comprehension, were scanned while viewing words relative to consonant letter strings. In normal subjects, this results in left lateralized activation in the posterior inferior frontal, middle temporal, and posterior inferior temporal cortices. Each patient activated normally in the middle temporal region but abnormally in the damaged posterior inferior frontal cortex and the undamaged posterior inferior temporal cortex. In the damaged frontal region, activity was insensitive to the presence of words but in the undamaged posterior inferior temporal region, activity decreased in the presence of words rather than increasing as it did in the normal individuals. The reversal of responses in the left posterior inferior temporal region illustrate the context-sensitive nature of the abnormality and that failure to activate the left posterior temporal region could not simply be accounted for by insufficient demands on the underlying function. We propose that, in normal individuals, visual word presentation changes the effective connectivity among reading areas and, in patients, posterior temporal responses are abnormal when they depend upon inputs from the damaged inferior frontal cortex. Our results serve to introduce the concept of dynamic diaschisis; the anatomically remote and context-sensitive effects of focal brain lesions. Dynamic diaschisis reveals abnormalities of functional integration that may have profound implications for neuropsychological inference, functional anatomy and, vicariously, cognitive rehabilitation.

Aphasia, Broca↗

Separate neural subsystems within 'Wernicke's area'.

Over time, both the functional and anatomical boundaries of 'Wernicke's area' have become so broad as to be meaningless. We have re-analysed four functional neuroimaging (PET) studies, three previously published and one unpublished, to identify anatomically separable, functional subsystems in the left superior temporal cortex posterior to primary auditory cortex. From the results we identified a posterior stream of auditory processing. One part, directed along the supratemporal cortical plane, responded to both non-speech and speech sounds, including the sound of the speaker's own voice. Activity in its most posterior and medial part, at the junction with the inferior parietal lobe, was linked to speech production rather than perception. The second, more lateral and ventral part lay in the posterior left superior temporal sulcus, a region that responded to an external source of speech. In addition, this region was activated by the recall of lists of words during verbal fluency tasks. The results are compatible with an hypothesis that the posterior superior temporal cortex is specialized for processes involved in the mimicry of sounds, including repetition, the specific role of the posterior left superior temporal sulcus being to transiently represent phonetic sequences, whether heard or internally generated and rehearsed. These processes are central to the acquisition of long- term lexical memories of novel words.

Acoustic Stimulation↗

Thrombolysis in acute ischaemic stroke.

In conclusion, thrombolysis with rtPA given within six hours of the onset of stroke in carefully selected patients is a safe therapy. However, efficacy has only been demonstrated within three hours after stroke onset. At present, only 6%-12% of all stroke patients are likely to be eligible for thrombolysis. Improved methods for investigating acute stroke, particularly magnetic resonance techniques, may improve the appropriate targeting of this treatment to those patients most likely to benefit. What is certain is that any increasing use of thrombolysis will have major effects on stroke services. The emphasis will have to be on early assessment and referral, if only to reach an imaging facility for a treatment decision to be made.

Acute Disease↗

MR diffusion tensor imaging of white matter tract disruption in stroke at 3 T.

Recent advances in MR diffusion weighted imaging (DWI) enable the identification of anisotropic white matter tracts with diffusion tensor imaging (DTI). We aimed to use a novel DTI technique to safely study patients with recent stroke in a high field (3 T) MR machine with its intrinsically higher spatial resolution and signal-to-noise ratio. Of ten patients studied, six had disruption of white matter tracts as determined by DTI. A further patient had distortion of white matter tracts around an infarct rather than actual disruption of the tracts themselves. The lack of tract destruction may imply a beneficial prognosis, information that is not available with conventional DWI.

Adult↗

A functional neuroimaging description of two deep dyslexic patients.

Deep dyslexia is a striking reading disorder that results from left-hemisphere brain damage and is characterized by semantic errors in reading single words aloud (e.g., reading 'spirit' as 'whisky'). Two types of explanation for this syndrome have been advanced. One is that deep dyslexia results from a residual left-hemisphere reading system that has lost the ability to pronounce a printed word without reference to meaning. The second is that deep dyslexia reflects right-hemisphere word processing. Although previous attempts to adjudicate between these hypotheses have been inconclusive, the controversy can now be addressed by mapping functional anatomy. In this study, we demonstrate that reading by two deep dyslexic patients (CJ and JG) involves normal or enhanced activity in spared left-hemisphere regions associated with naming (Broca's area and the left posterior inferior temporal cortex) and with the meanings of words (the left posterior temporo-parietal cortex and the left anterior temporal cortex). In the right-hemisphere homologues of these regions, there was inconsistent activation within the normal group and between the deep dyslexic patients. One (CJ) showed enhanced activity (relative to the normals) in the right anterior inferior temporal cortex, the other (JG) in the right Broca's area, and both in the right frontal operculum. Although these differential right-hemisphere activations may have influenced the reading behavior of the patients, their activation patterns primarily reflect semantic and phonological systems in spared regions of the left hemisphere. These results preclude an explanation of deep dyslexia in terms of purely right-hemisphere word processing.

Brain Mapping↗

Hearing and saying. The functional neuro-anatomy of auditory word processing.

The neural systems involved in hearing and repeating single words were investigated in a series of experiments using PET. Neuropsychological and psycholinguistic studies implicate the involvement of posterior and anterior left perisylvian regions (Wernicke's and Broca's areas). Although previous functional neuroimaging studies have consistently shown activation of Wernicke's area, there has been only variable implication of Broca's area. This study demonstrates that Broca's area is involved in both auditory word perception and repetition but activation is dependent on task (greater during repetition than hearing) and stimulus presentation (greater when hearing words at a slow rate). The peak of frontal activation in response to hearing words is anterior to that associated with repeating words; the former is probably located in Brodmann's area 45, the latter in Brodmann's area 44 and the adjacent precentral sulcus. As Broca's area activation is more subtle and complex than that in Wernicke's area during these tasks, the likelihood of observing it is influenced by both the study design and the image analysis technique employed. As a secondary outcome from the study, the response of bilateral auditory association cortex to 'own voice' during repetition was shown to be the same as when listening to "other voice' from a prerecorded tape.

Auditory Perception↗

Changes in urate metabolism after castration of patients suffering from carcinoma of the prostate.

13 patients with carcinoma of the prostate were investigated on a low purine diet before and after surgical castration, performed to slow progression of their disease. A control group of herniorrhaphy patients was similarly studied. The 2 groups were very similar pre-operatively except for urea which was higher pre-operatively in patients than controls (p0.004). Testosterone levels fell significantly in patients soon after surgery (W0.002). There was a significant fall in serum uric acid in the early post-operative phase in both patients (W0.004) and controls (W0.01) but the fall only remained significant one month after surgery in castrated patients (W0.007). Urinary uric acid levels in patients fell significantly soon after surgery (W0.04). This is a small study but results suggest that endogenous male hormones are at least partially responsible for serum uric acid levels since castration, with reduction in circulating testosterone, resulted in a fall in these levels.

Creatinine↗