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Biomedical subjects

Philip A Barber

Publications and source records attributed to Philip A Barber.

At least 19 recordsLinked to original sources
PubMed2006

Asymptomatic hemorrhage after thrombolysis may not be benign: prognosis by hemorrhage type in the Canadian alteplase for stroke effectiveness study registry.

BACKGROUND AND PURPOSE: There is ongoing controversy about the impact of hemorrhagic transformation after thrombolysis on long-term functional outcome. We sought to study the relation between the type of hemorrhagic transformation on CT scans and functional outcome. METHODS: Data were obtained from the Canadian Alteplase for Stroke Effectiveness Study. This study was established as a registry to prospectively collect data for acute stroke patients receiving intravenous alteplase within 3 hours from stroke onset between February 1999 and June 2001. Follow-up was completed at 90 days, and good functional outcome was defined as a modified Rankin Scale score of 0 or 1. Copies of head CT scans obtained at 24 to 48 hours after starting treatment were read in consensus by a central reading panel consisting of 1 neuroradiologist and 1 stroke neurologist. According to European Cooperative Acute Stroke Study criteria, hemorrhagic transformation was classified as none, hemorrhagic infarction (HI-1 and HI-2), or parenchymal hematoma (PH-1 and PH-2). We compared outcome across groups and performed a multivariable analysis including previously determined important predictors of good outcome in acute ischemic stroke. RESULTS: From 1135 patients enrolled at 60 centers across Canada, 954 follow-up CT scans were assessable. We observed some hemorrhagic transformation in 259 of 954 (27.1%) patients (110 HI-1, 57 HI-2, 48 PH-1, and 44 PH-2). Proportions of patients with good outcome were 41% with no hemorrhagic transformation, 30% with HI-1, 17% with HI-2, 15% with PH-1, and 7% with PH-2 (P<0.0001, chi(2) test). After adjustment for age, baseline serum glucose, baseline Alberta Stroke Program Early CT score, and baseline National Institutes of Health Stroke Scale score, HI-1 was not a predictor of outcome. However, HI-2 (odds ratio=0.38, 95% CI=0.17 to 0.83), PH-1 (odds ratio=0.32, 95% CI=0.12 to 0.80), and PH-2 (odds ratio=0.14, 95% CI=0.04 to 0.48) were all negative predictors of outcome. CONCLUSIONS: The likelihood of a poor outcome after thrombolysis was proportional to the extent of hemorrhage on CT scans. HI grades of hemorrhagic transformation may not be benign.

Adult↗
PubMed2006

Improved regional cerebral blood flow is important for the protection seen in a mouse model of late phase ischemic preconditioning.

INTRODUCTION: Ischemic preconditioning (IPC) induces protection to cerebral ischemia. However, it was previously unclear whether this protection resulted from altered susceptibility to ischemia. The current study examines the effects of late phase ischemic preconditioning in a mouse model of middle cerebral artery occlusion (MCAO). Specific examination of the regional cerebral blood flow (rCBF) was conducted. EXPERIMENTAL PROCEDURE: Intra-abdominal radiofrequency probes were implanted in animals and core temperature was regulated. Mice were subjected to MCAO: (1) brief 15 min duration (preconditioning ischemia) and (2) 45 min MCAO (injurious ischemia). Naive (i.e. not preconditioned) animals were compared with preconditioned animals (preconditioning ischemia plus injurious ischemia at 72 h reperfusion). rCBF was measured using laser Doppler flowmetry (LDF) and magnetic resonance cerebral perfusion (MRP) arterial spin labeling. Percentage of brain infarcted was compared between groups. RESULTS: rCBF was significantly improved in the preconditioned cohorts of mice. Naive animals showed flow reductions to 16+/-3.59% (MCAO_45; injurious, unpreconditioned) and 17.1+/-8.6% (MCAO_15; preconditioning ischemia alone) of baseline, while preconditioned animals had flows 33.9+/-13.2% (IPC_45; preconditioned animals with injurious ischemia at 72 h reperfusion) of baseline (p=0.001). Percentage of brain infarcted was 17.2+/-6.2% in naive animals, while it was 5.1+/-4.6% in the preconditioned animals (p=0.003). MRP of the perfusion to the ischemic hemisphere, in a striatal coronal slice of the brain was 26.7+/-5.8% of the contralateral hemisphere in naive animals while preconditioned mice had flows of 38.7+/-6.8% of contralateral (p=0.04). CONCLUSIONS: Improved rCBF is an important factor in the protection of IPC, during injurious MCAO in the mouse. Stringent monitoring of rCBF is required in future studies of IPC.

Animals↗
PubMed2006

Diabetes, leukoencephalopathy and rage.

Longstanding diabetes mellitus damages kidney, retina, peripheral nerve and blood vessels, but brain is not usually considered a primary target. We describe direct involvement of the brain, particularly white matter, in long-term (9 months) experimental diabetes of mice, not previously modeled, correlating magnetic resonance (MR) imaging with quantitative histological assessment. Leukoencephalopathy and cerebral atrophy, resembling that encountered in diabetic humans, developed in diabetic mice and was accompanied by time-related development of cognitive changes in behavioural testing. Increased RAGE (receptor for advanced glycation end products) expression, a mediator of widespread diabetic complications, increased dramatically at sites of white matter damage in regions of myelination. RAGE expression was also elevated within neurons, astrocytes and microglia in grey matter and within oligodendrocytes in white matter. RAGE null diabetic mice had significantly less neurodegenerative changes when compared to wild-type diabetic mice. Our findings identify a robust and novel model of cerebral, particularly white matter, involvement with diabetes associated with abnormal RAGE signaling.

Animals↗
PubMed2005

Early T1- and T2-weighted MRI signatures of transient and permanent middle cerebral artery occlusion in a murine stroke model studied at 9.4T.

Early reperfusion following stroke results in reduced tissue injury. Paradoxically, restoration of blood flow under certain conditions may also cause delayed neuronal damage (reperfusion injury). The interrelationship of changes in T1, T2 and diffusion weighted images of tissue water were studied in mouse models of permanent and transient focal cerebral ischemia. A sham surgery or either permanent or transient (30 min) middle cerebral artery occlusion (MCAO) were induced in 14 mice. Magnetic resonance (MR) images of the brain were acquired including: T2 maps, T1 maps and diffusion weighted spin-echo images to produce apparent diffusion coefficient of water apparent diffusion coefficient (ADC) maps. Images were collected on average 90 min after MCAO in both the transient and permanent ischemia groups. Scans were repeated at 24h post-occlusion in mice with transient ischemia. Permanent MCAO resulted in decreases in ADC and no significant change in T2 acutely following MCAO. There were increases in T1 compared to sham controls within the ischemic region in mice following either transient or permanent MCAO (P<0.001). In contrast to permanent MCAO, there were increases in T2 (P<0.001) in the infarct area present in the reperfusion phase within 90 min of transient MCAO. There was considerable infarct growth at 24h (P<0.001). This study demonstrates that following either type of occlusion there are early increases in T1 suggesting an elevated water content in the stroke lesion, while only following transient MCAO are there early increases in T2, indicative of early vasogenic oedema with breakdown of the blood-brain barrier.

Animals↗
PubMed2005

Importance of early ischemic computed tomography changes using ASPECTS in NINDS rtPA Stroke Study.

BACKGROUND AND PURPOSE: The importance of early ischemic change (EIC) on baseline computed tomography (CT) in the decision to thrombolyze the patient with acute ischemic stroke has been controversial. ASPECTS is a semiquantitative scale that scores the extent of EIC within the middle cerebral artery territory. We examined whether ASPECTS could be a treatment modifier by systematically reviewing the CT scans in the NINDS rtPA Stroke Study. METHODS: Six hundred eight of the 624 CT scans were available and of sufficient quality. One of 2 teams (n=3 each) of expert ASPECTS readers evaluated each scan for an ASPECTS value using a consensus score approach. Each team was blind to all clinical information except symptom side and blind to follow-up imaging and outcome information. ASPECTS values were stratified before analysis. Multivariable logistic regression was used to determine if an ASPECTS by treatment interaction existed on treatment response, outcome, and intracerebral hemorrhage risk. RESULTS: A total of 57.2% (348 of 608) of scans showed EIC with an ASPECTS <10. ASPECTS dichotomized into 8 to 10 and <8 did not have a treatment-modifying effect on good outcome but showed a trend to lower mortality at 90 days with tPA (relative risk 0.67, 95% confidence interval 0.41 to 1.06, P=0.10). ASPECTS 8 to 10 were associated with a trend to larger benefit of tPA with a number needed to treat (NNT) of 5 versus ASPECTS 3 to 7 with a NNT of 8. CONCLUSIONS: There was no evidence of treatment effect modification by the baseline ASPECTS value in the NINDS rtPA Stroke Study. Therefore, exclusion of patients for thrombolysis within 3 hours of symptom onset based on EIC is not supported by our data. There is a trend to reduced mortality and increased benefit to rtPA if the baseline CT scan is favorable (ASPECTS >7).

Aged↗
PubMed2005

Triaging transient ischemic attack and minor stroke patients using acute magnetic resonance imaging.

We examined whether the presence of diffusion-weighted imaging (DWI) lesions and vessel occlusion on acute brain magnetic resonance images of minor stroke and transient ischemic attack patients predicted the occurrence of subsequent stroke and functional outcome. 120 transient ischemic attack or minor stroke (National Institutes of Health Stroke Scale < or = 3) patients were prospectively enrolled. All were examined within 12 hours and had a magnetic resonance scan within 24 hours. Overall, the 90-day risk for recurrent stroke was 11.7%. Patients with a DWI lesion were at greater risk for having a subsequent stroke than patients without and risk was greatest in the presence of vessel occlusion and a DWI lesion. The 90-day risk rates, adjusted for baseline characteristics, were 4.3% (no DWI lesion), 10.8% (DWI lesion but no vessel occlusion), and 32.6% (DWI lesion and vessel occlusion) (p = 0.02). The percentages of patients who were functionally dependent at 90 days in the three groups were 1.9%, 6.2%, and 21.0%, respectively (p = 0.04). The presence of a DWI lesion and a vessel occlusion on a magnetic resonance image among patients presenting acutely with a transient ischemic attack or minor stroke is predictive of an increased risk for future stroke and functional dependence.

Acute Disease↗
PubMed2005

Bedside emergency transcranial Doppler diagnosis of severe carotid disease using orbital window examination.

BACKGROUND: Identifying internal carotid artery (ICA) stenosis in the acute stroke setting can provide clinically useful information. Transcranial Doppler (TCD) through the orbital window is an easy test to perform and to track and identify different vessels. Previous TCD studies have suggested that a reversed ophthalmic artery (OA) flow is a useful collateral pattern to predict ICA disease. The authors sought to evaluate the TCD orbital window for predicting cervical ICA (cICA) stenosis in the setting of acute stroke and TIA. METHOD: Power M-mode/TCD was performed in acute stroke and transient ischemic attack patients at 2 institutions. Each orbital window depth was detected on M-mode and evaluated for the direction of flow and resistance pattern. Gold standard for comparison was carotid evaluation using carotid duplex, computed tomography angiogram, or conventional angiography. The assessment of cICA disease was categorized by degree of stenosis or occlusion. RESULTS: A total of 216 transorbital exams were performed in 117 patients. Twenty-five cICA occlusions and 8 critical cICA stenoses (>or=95%) were identified by gold standard imaging. Reversed OA flow at 50 to 60 mm depth revealed high specificity (100%; confidence interval [CI], 97.6%-100.0%) and good sensitivity (75%; CI, 53.3%-90.2%) for identifying cICA occlusion or critical stenosis (>or=95%). Low pulsatility index (<1.2) and mean flow velocity (<15 cm/s) discriminated critical severe ICA stenosis or occlusion when OA flow was anterograde with good sensitivity (87.2%) and specificity (95.2%). CONCLUSION: The reversed OA sign at 50 to 60 mm depth is very specific for identifying cICA occlusion or critical stenosis. When OA flow is anterograde, a low mean flow velocity or pulsatility index is also useful to identify cICA critical stenosis or occlusion.

Carotid Artery, Internal↗
PubMed2004

Temperature-regulated model of focal ischemia in the mouse: a study with histopathological and behavioral outcomes.

BACKGROUND AND PURPOSE: The importance of mouse stroke models has increased with the development of genetically manipulated animals. We hypothesized that immediate postischemia hypothermia may attenuate ischemic brain injury in the mouse. METHODS: Intraabdominal radio frequency probes were implanted in animals and core temperature monitored. Groups included: MCAO-45-REG (45 minutes middle cerebral artery occlusion [MCAO]) temperature-controlled in the postischemic period >34 degrees C for 24 hours; MCAO-45 (45 minutes MCAO) were allowed to self-regulate core temperature during recovery; MCAO-30-REG (30 minutes MCAO), with the same temperature protocol as MCAO-45-REG; MCAO-30 (30 minutes MCAO), with temperature protocol the same as MCAO-45. Behavior and histological score was assessed at 7 days. The qualitative histological score assessed for injury in 18 specified regions. RESULTS: MCAO-45-REG core temperature (mean 34.94 degrees C+/-0.8 degrees C) was significantly different than the self-regulating (MCAO-45, mean 33.1 degrees C+/-2.3 degrees C) for the first 4 hours after anesthesia (P<0.01). There was a trend toward similar differences in temperatures for MCAO-30-REG and MCAO-30 (P=0.08). At 7 days, a greater improvement in behavior score was observed for MCAO-45 and MCAO-30 compared with MCAO-45-REG and MCAO-30-REG (P<0.001). The histological score confirmed reduced injury in unregulated temperature groups (MCAO-45-REG mean 38+/-10 and MCAO-45 30+/-5.1, P<0.05; MCAO-30-REG 41+/-10 and MCAO-30 30+/-9, P<0.05). CONCLUSIONS: Hypothermia is an important confounder of stroke injury in the intraluminal filament mouse model. Future mouse stroke studies must use strict temperature regulation.

Animals↗
PubMed2004

Interobserver variation of ASPECTS in real time.

BACKGROUND: The Alberta Stroke Program Early CT Score (ASPECTS) has been used to quantify early ischemic changes on computed tomography (CT) brain scans of acute stroke patients. We sought to assess the reliability of the score when performed in real time as compared with an expert rating performed at a later time point. METHODS: Two hundred fourteen patients presenting with acute ischemic stroke or transient ischemic attack were prospectively recruited if they had a brain CT scan performed within 12 hours of symptom onset. Each scan was read for ASPECTS prospectively by the treating physician and later by 1 expert reader. A weighted kappa statistic was used to determine the interobserver agreement. RESULTS: The median baseline National Institutes of Health Stroke Scale score was 5 (range: 0 to 32) and the median time to CT scan was 152 minutes (range: 22 to 769). The interobserver agreement between ASPECTS performed in real time and expert ASPECTS was substantial (kappa(w)=0.69). The mean difference between real-time ASPECTS and expert ASPECTS was 0 (SD: 1.1). CONCLUSIONS: ASPECTS is a reliable clinical scale for rating early ischemic changes on CT when performed in real time.

Adult↗
PubMed2004

Mild neurological symptoms despite middle cerebral artery occlusion.

BACKGROUND AND PURPOSE: Only a small percentage of stroke patients are treated with thrombolytic therapy. We sought to determine whether vessel occlusion in mild strokes represented a new target population for interventional therapy. METHODS: We imaged 106 acute stroke patients with MRI. Patients were identified with evidence of middle cerebral artery (MCA) occlusion and mild or no stroke signs (National Institutes of Health Stroke Scale [NIHSS] 3, and MCA occlusion. RESULTS: We identified 5 patients with absent flow on MRA in the MCA and mild or no stroke signs (NIHSS <or=3). All 5 were functionally independent at 3 months. CONCLUSIONS: Caution should be exercised in considering thrombolytic therapy in these patients. Quantification of perfusion imaging is required to identify "at risk" mild stroke populations.

Acute Disease↗
PubMed2004

MR molecular imaging of early endothelial activation in focal ischemia.

Focal ischemia followed by reperfusion initiates a harmful P- and E-selectin-mediated recruitment of leukocytes in brain microvasculature. In this study, we tested whether a novel magnetic resonance (MR) contrast agent (Gd-DTPA-sLe(x) A), which is designed to bind to activated endothelium could be detected by MR imaging (MRI) in a focal stroke mouse model. MRIs (9.4T) of the brain were acquired 24 hours after transient middle cerebral artery occlusion. T1 maps were acquired repeatedly before and up to 1.5 hours after the intravenous injection of either Gd-DTPA or Gd-DTPA-sLe(x) A. Analysis of images included a pixel-by-pixel subtraction of T1 maps from the precontrast T1 maps and quantification of T1 within the ischemic area. After injection of Gd-DTPA-sLe(x) A, T1 decreased compared with precontrast levels, and an interhemispheric difference between the pre-post contrast T1 developed within the stroke lesion at a mean time of 52 minutes after injection (p < 0.05). Animals injected with Gd-DTPA did not exhibit changes in T1 signal intensity between regions of the ipsilateral and contralateral hemispheres, indicating that the reductions in T1 observed with Gd-DTPA-sLe(x) A were unrelated to blood-brain barrier breakdown. Fluorescent-labeled sLe(x) A administered intravenously was observed to bind to the endothelium of injured but not control brain. The study suggests that the contrast agent Gd-DTPA-sLe(x) A can be used to visualize early endothelial activation after transient focal ischemia in vivo with MRI.

Animals↗
PubMed2003

Reliability of assessing percentage of diffusion-perfusion mismatch.

BACKGROUND AND PURPOSE: Emergent neurovascular imaging holds promise in identifying new and optimum target populations for thrombolysis in stroke. Recent research has focused on patients with diffusion-weighted MRI (DWI)-perfusion-weighted MRI (PWI) mismatch as a marker of tissue at risk of infarction and a means to select the most suitable candidates for thrombolysis. The present study sought to estimate the reliability of assessing the percentage of DWI-PWI mismatch. METHODS: Thirteen patients with acute strokes had DWI and PWI within 7 hours of symptom onset. Six raters independently created relative mean transit time (rMTT) maps and then compared them with DWI images to assess the percentage of mismatch (PWI>DWI) in 10% increments. The MR scans were reassessed by 4 raters, tracing around the lesions to calculate the volume percentage of mismatch. RESULTS: Visual assessment had an interrater reliability of 0.68 (95% CI, 0.52 to 1.0; SEM=21.6%) and an intrarater reliability of 0.80 (95% CI, 0.47 to 1.0; SEM=16.9%). Hand-drawn assessment had an interrater reliability of 0.66 (95% CI, 0.45 to 1.0; SEM=26.2%) and an intrarater reliability of 0.94 (95% CI, 0.81 to 1.0; SEM=10.9%). CONCLUSIONS: Results from the present study suggest that quantifying mismatch by the human eye is reproducible but not reliable among observers. This raises doubts about using mismatch for clinical decision making and clinical trial enrollment.

Acute Disease↗
PubMed2003

Computed tomographic parameters predicting fatal outcome in large middle cerebral artery infarction.

BACKGROUND: Large middle cerebral artery (MCA) ischaemic stroke when associated with extensive mass effect can result in brain herniation and neurological death. As yet there are few guidelines to aid the selection of patients for aggressive interventional therapies, such as decompression hemicraniectomy and/or hypothermia. METHODS: We studied a cohort of patients from seven centres with large MCA infarction requiring neurocritical care. The purpose of this analysis was to assess the use of early radiological signs on follow-up computed tomographic (CT) signs performed within 48 h of stroke onset for predicting mortality at 30 days. The CT parameters assessed included horizontal displacement of the septum pellucidum, pineal shift, complete or partial infarction of the temporal lobe, involvement of additional vascular territories, and the presence of hydrocephalus. The primary outcome measure was in-hospital death within 30 days. RESULTS: One hundred and thirty-five patients who had follow-up CT scans within 48 h were identified from a total of 201 patients with large MCA infarction that received conventional medical therapy alone. The median age was 68 (range 29-99), 56% were female, and the median NIHSS category was 26-30 at 48 h. Among CT variables in univariable analysis, anteroseptal shift >/=5 mm, pineal shift >/=2 mm, complete temporal lobe infarction, involvement beyond the MCA territory, and moderate or severe hydrocephalus were equally predictive of death. Multivariable analysis adjusting for time to CT scan revealed the following predictors of fatal outcome: anteroseptal shift >/=5 mm (OR 10.9; 95% CI 3.2-37.6), NIHSS within 48 h >20 (OR 6.6; 95% CI 2.3-19.3), and infarction beyond the MCA territory (OR 4.9; 95% CI 1.6-15.0). CONCLUSIONS: We identified the role of early CT signs in predicting death following massive MCA infarction. The CT parameters anteroseptal shift (>5 versus </=5 mm), pineal shift >/=2 mm, hydrocephalus, temporal lobe infarction, and other vascular territory infarction if present were predictive of fatal outcome. These CT parameters require prospective validation before they should be considered reliable markers for decision-making.

Adult↗