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Biomedical subjects

A E Baird

Publications and source records attributed to A E Baird.

At least 19 recordsLinked to original sources

A three-item scale for the early prediction of stroke recovery.

BACKGROUND: Accurate assessment of prognosis in the first hours of stroke is desirable for best patient management. We aimed to assess whether the extent of ischaemic brain injury on magnetic reasonance diffusion-weighted imaging (MR DWI) could provide additional prognostic information to clinical factors. METHODS: In a three-phase study we studied 66 patients from a North American teaching hospital who had: MR DWI within 36 h of stroke onset; the National Institutes of Health Stroke Scale (NIHSS) score measured at the time of scanning; and the Barthel Index measured no later than 3 months after stroke. We used logistic regression to derive a predictive model for good recovery. This logistic regression model was applied to an independent series of 63 patients from an Australian teaching hospital, and we then developed a three-item scale for the early prediction of stroke recovery. FINDINGS: Combined measurements of the NIHSS score (p=0.01), time in hours from stroke onset to MR DWI (p=0.02), and the volume of ischaemic brain tissue on MR DWI (p=0.04) gave the best prediction of stroke recovery. The model was externally validated on the Australian sample with 0.77 sensitivity and 0.88 specificity. Three likelihood levels for stroke recovery-low (0-2), medium (3-4), and high (5-7)-were identified on the three-item scale. INTERPRETATION: The combination of clinical and MR DWI factors provided better prediction of stroke recovery than any factor alone, shortly after admission to hospital. This information was incorporated into a three-item scale for clinical use.

Activities of Daily Living↗

Relationship between magnetic resonance arterial patency and perfusion-diffusion mismatch in acute ischemic stroke and its potential clinical use.

BACKGROUND: In patients with acute ischemic stroke the magnetic resonance (MR) perfusion-diffusion mismatch pattern (perfusion lesion at least 20% larger than the lesion on diffusion-weighted imaging) may indicate ischemically threatened but viable tissue. To our knowledge, the relationship of this MR pattern to serial changes in MR angiography (MRA) has not been reported. OBJECTIVES: To investigate the relationship between MRA changes and patterns of diffusion-weighted imaging and perfusion abnormalities and to determine if the information obtained could be used in clinical management. METHODS: The MR studies of 35 patients who had undergone sequential multimodality MR imaging studies within the first 4 days of stroke were reviewed. All lesions were in the internal carotid artery territory distribution. Magnetic resonance angiographies were read by 2 observers blinded to the clinical data. RESULTS: During the first 24 hours a perfusion-diffusion mismatch was present in 22 (92%) of the 24 patients with an MRA arterial occlusive lesion. (At this time 5 [46%] of the 11 patients with a normal MRA [P =.006] also had a mismatch.) Two to 4 days after stroke, of these 22 patients resolution of the mismatch occurred in 8 (87%) of 9 patients with recanalization on MRA compared with 5 (39%) of 13 patients without arterial recanalization (P =.03). Resolution of mismatch occurred in 3 (60%) of 5 patients with a normal MRA and a mismatch at the first time point. CONCLUSIONS: Concordance between MRA and the MR perfusion-diffusion mismatch pattern provides supportive evidence for an arterial vascular basis for this MR signature in acute stroke. Discordance between MRA lesions and mismatch may result from arterial branch occlusions undetected by MRA or from an alternate mechanism for the mismatch. The MR imaging patterns identified extend our understanding of the pathophysiology of stroke and may contribute to the improvement of stroke management in the future.

Acute Disease↗

Prediction of the final infarct volume within 6 h of stroke using single photon emission computed tomography with technetium-99m hexamethylpropylene amine oxime.

BACKGROUND: A simple method to predict the final infarct volume within 6 h of onset of hemispheric ischemic stroke based on the measurement of cerebral blood flow (CBF) using single photon emission computed tomography (SPECT) with techneticum-99m hexamethylpropylene amine oxime ((99m)Tc-HMPAO) was investigated in a clinical model involving patients without definite early reperfusion or clinical recovery. METHODS: A group of 16 patients (group 1) was used to establish the methodology, which was then validated in a second group of 14 patients (group 2). The final infarct volume was defined using computed tomography (CT) performed at least 7 days after stroke. The relative CBF threshold value, expressed as a percentage of the mean contralateral hemispheric value, which most closely estimated the final infarct size on coregistered CT was established for each patient. RESULTS: The mean threshold CBF value for group 1 was 63.7%. When this value was used to predict infarct size in group 2, a close correlation was observed between the actual and the estimated sizes (r = 0.973, p < 0.0001). This value was not time dependent. CONCLUSIONS: If no significant early reperfusion or clinical recovery occurs, a CBF threshold value of 63.7% on (99m)Tc-HMPAO SPECT performed within 6 h of stroke onset will reliably predict the final infarct size.

Aged↗

Multiple acute stroke syndrome: marker of embolic disease?

OBJECTIVE: To determine the frequency and etiologic significance of multiple acute ischemic lesions in stroke. BACKGROUND: Although patients may have more than one stroke during the course of their lives, acute ischemic stroke is usually thought of as a single event. Using diffusion-weighted imaging (DWI), an MRI technique that detects ischemic injury within minutes after onset, we have often observed multiple acute ischemic lesions. METHODS: The MRI scans of 59 consecutively studied patients were reviewed to determine the frequency and etiologic significance of multiple acute ischemic lesions on DWI. RESULTS: Multiple acute ischemic lesions were present in 10 (17%) of 59 patients. The lesions usually occurred within one major circulation (anterior or posterior), but in two patients (3%), lesions occurred in both cerebral hemispheres or in the anterior and the posterior circulations. The lesions often were small and resulted from presumed multiple emboli or the break-up of an embolus. Two patients had internal carotid artery occlusive disease and four had a cardiac or aortic source. In the other four patients the source was not determined. Lesions larger than 1 cm in diameter progressed to infarction, but some smaller lesions were not seen on follow-up T2-weighted imaging. CONCLUSIONS: Multiple acute stroke lesions on DWI are common and could be caused by multiple emboli or the breakup of an embolus. In some cases it might become possible to make early inferences concerning the stroke mechanism that could be of use for immediately directing the clinical work-up and treatment of the patient.

Acute Disease↗

Enteral nutrition and corticosteroids in the treatment of acute Crohn's disease in children.

BACKGROUND: The optimal treatment of acute Crohn's disease in children remains controversial. In adults, steroid therapy has been shown to be superior to exclusive enteral nutrition. However, enteral nutrition is effective at inducing a remission in many children with acute Crohn's disease. Steroid usage in children has been associated with adverse side effects, particularly with delayed growth and pubertal development. METHODS: Randomized clinical trials comparing exclusive enteral nutrition with corticosteroids were identified. Two independent reviewers extracted data from selected studies. Studies were assessed for heterogeneity and relative risks for remission induction with enteral nutrition were obtained. Sensitivity analyses were performed in partially randomized studies. Estimates were made of the number of studies needed to overturn the current result. Other outcome measures were qualitatively assessed. RESULTS: In five randomized clinical trials comprising 147 patients, enteral nutrition was as effective as corticosteroids at inducing a remission (RR = 0.95 [95% confidence interval 0.67, 1.34]). Addition of two further nonrandomized trials did not significantly alter the result. A minimum of 10 further studies, equal in size and outcome to the largest reported pediatric trial to date (n = 68, RR = 0.84), would be required to demonstrate a significant benefit of steroid therapy over enteral nutrition. CONCLUSIONS: There is no difference in efficacy between enteral nutrition and corticosteroid therapy in the treatment of acute Crohn's disease in children. Improved growth and development, without the side effects of steroid therapy, make enteral nutrition a better choice for first-line therapy in children with active Crohn's disease.

Acute Disease↗

The ischemic penumbra: operationally defined by diffusion and perfusion MRI.

BACKGROUND: Identifying tissue at risk for infarction is important in deciding which patients would benefit most from potentially harmful therapies and provides a way to evaluate newer therapies with regard to the amount of ischemic tissue salvaged. OBJECTIVE: To operationally define and characterize cerebral tissue at risk for stroke progression. METHODS: We retrospectively selected 25 patients with an acute onset of a hemispheric stroke from our database who had undergone a combination of two diffusion-weighted MRI studies and a perfusion-weighted MRI study. We applied a logistic regression model using maps of the relative mean transit time and relative cerebral blood flow (rCBF) as well as three different maps of the relative cerebral blood volume (rCBV) to predict an operationally defined penumbra (region of mismatch between the diffusion lesion on day 1 and its extension 24 to 72 hours later). RESULTS: Maps of the rCBF and initial rCBV were significant predictors for identifying penumbral tissue. Our operationally defined penumbral region was characterized by a reduction in the initial rCBV (47% of contralateral control region [CCR]), an increase (163% of CCR) in the total rCBV, and a reduction (37% of CCR) in the rCBF, whereas the operationally defined ischemic core showed a more severe reduction in the rCBF (12% of CCR) and in the initial rCBV (19% of CCR). CONCLUSION: These MR indexes may allow the identification and quantification of viable but ischemically threatened cerebral tissue amenable to therapeutic interventions in the hyperacute care of stroke patients.

Aged↗

Imaging developing brain infarction.

Continued advances in neuroimaging technology have made it practical to image multiple aspects of evolving brain infarction during the potential window period of therapeutic opportunity in stroke. Recent methodologic developments include computed tomography angiography and perfusion, and the description of quantitative parameters for magnetic resonance blood oxygen level-dependent perfusion imaging. In pathophysiologic studies, metabolism and function in the ischemic focus and the peri-infarct tissue have been further characterized. Clinical studies have focused on the applications of computed tomography and magnetic resonance imaging for prethrombolysis patient selection. These methods have an important role in the evaluation and development of new pharmaceutical agents and will be increasingly used in clinical practice as new therapies become available.

Brain↗

Magnetic resonance imaging of acute stroke.

In the investigation of ischemic stroke, conventional structural magnetic resonance (MR) techniques (e.g., T1-weighted imaging, T2-weighted imaging, and proton density-weighted imaging) are valuable for the assessment of infarct extent and location beyond the first 12 to 24 hours after onset, and can be combined with MR angiography to noninvasively assess the intracranial and extracranial vasculature. However, during the critical first 6 to 12 hours, the probable period of greatest therapeutic opportunity, these methods do not adequately assess the extent and severity of ischemia. Recent developments in functional MR imaging are showing great promise for the detection of developing focal cerebral ischemic lesions within the first hours. These include (1) diffusion-weighted imaging, which provides physiologic information about the self-diffusion of water, thereby detecting one of the first elements in the pathophysiologic cascade leading to ischemic injury; and (2) perfusion imaging. The detection of acute intraparenchymal hemorrhagic stroke by susceptibility weighted MR has also been reported. In combination with MR angiography, these methods may allow the detection of the site, extent, mechanism, and tissue viability of acute stroke lesions in one imaging study. Imaging of cerebral metabolites with MR spectroscopy along with diffusion-weighted imaging and perfusion imaging may also provide new insights into ischemic stroke pathophysiology. In light of these advances in structural and functional MR, their potential uses in the study of the cerebral ischemic pathophysiology and in clinical practice are described, along with their advantages and limitations.

Animals↗

Spontaneous reperfusion after ischemic stroke is associated with improved outcome.

BACKGROUND AND PURPOSE: The rationale behind thrombolytic therapy in acute ischemic stroke is penumbral salvage by rapid restoration of cerebral blood flow. The relationship, however, between early reperfusion (potentially composed of both nutritional and nonnutritional components) and outcome remains unclear. METHODS: To establish the relationship between reperfusion parameters and outcome variables (Canadian Neurological Scale, Barthel Index, outcome CT scans), we used 99Tc-hexamethylpropyleneamine oxime (99Tc-HMPAO) single-photon emission CT (SPECT) to examine 41 acute ischemic stroke patients. All patients had at least 2 SPECT studies (24 with 3 studies), and none had been treated with thrombolytic or other acute investigational drugs. RESULTS: A total of 106 studies were performed. Mean time to acute study was 9.2 hours; that for subacute study was 42 hours and for outcome study was 150 days. Hypoperfusion (HP) volumes at each of the 3 time points correlated with outcome clinical state and final infarct size. Both early reperfusion (61% of patients) and nutritional reperfusion alone (56%), which is early reperfusion maintained at outcome, were associated with improvement in clinical state and better functional outcome. Early HP volume change (acute minus subacute HP volume) and total HP volume change (acute minus outcome HP volume) also correlated with clinical improvement and better outcome. CONCLUSIONS: This study establishes the benefit of spontaneous reperfusion after ischemic stroke and emphasizes the prognostic value of HP deficit volumes. 99Tc-HMPAO SPECT may be used to screen patients and group them according to perfusion deficit in acute stroke trials, thereby decreasing patient numbers required to show drug effect.

Adult↗

Streptokinase in acute stroke: effect on reperfusion and recanalization. Australian Streptokinase Trial Study Group.

The Australian Streptokinase Trial was a randomized, double-blind, placebo-controlled trial, in which streptokinase (SK, 1.5 million IU I.V.) was given within 4 hours of stroke onset. In a subset of 37 patients, 99mTc-labeled D,L-hexamethylpropylene amine oxime single-photon emission computed tomography (SPECT) and/or transcranial Doppler (TCD) studies were performed before and after therapy to test the hypothesis that SK may improve the hemodynamic measures of reperfusion/recanalization rates (TCD parameter) within 24 hours. Eighteen patients received SK and 19 placebo. Baseline characteristics were similar in both groups, and there were no differences in clinical outcomes assessed at 3 months after stroke. Although there was no increase in the group mean perfusion defect or volume on SPECT after thrombolytic therapy, a larger number of patients demonstrating the combined end point of reperfusion or recanalization was seen in the SK group (13/14, 93%) than in the placebo group (7/14, 50%; p = 0.01). Although SK given within 4 hours of acute ischemic stroke appears to improve arterial patency/tissue reperfusion, this effect is neither early nor extensive enough to influence overall clinical outcome.

Acute Disease↗

Turbo spin-echo diffusion-weighted MR of ischemic stroke.

PURPOSE: Our objective was to determine whether a multisection technique, diffusion-weighted half-Fourier single-shot turbo spin-echo (HASTE) imaging, can compensate for the drawbacks common to other diffusion-weighted techniques; specifically, the need for echo-planar technology and the presence of susceptibility artifacts in areas close to the skull base. METHODS: Forty subjects who were referred to the stroke service with signs of acute (less than 24 hour) neurologic dysfunction were included in this prospective study. MR imaging of the brain was performed with diffusion-weighted echo-planar and diffusion-weighted HASTE sequences. The images obtained with both sequences were analyzed for the presence of hyperintensities corresponding to ischemic lesions as well as for the presence of image artifacts and distortions. RESULTS: Diffusion-weighted HASTE images showed areas of hyperintensity corresponding to the infarcts present on diffusion-weighted echo-planar imaging studies without distortion or susceptibility artifacts in all the patients who had a stroke. Twelve patients had no acute ischemic lesions; of these, five had other findings, six had normal findings, and in one patient, a hyperintensity seen on diffusion-weighted echo-planar images proved to be an artifact on diffusion-weighted HASTE images. CONCLUSIONS: Diffusion-weighted HASTE is equal to diffusion-weighted echo-planar imaging in the detection of early ischemia. Because of the absence of significant image distortions and other artifacts, diffusion-weighted HASTE permits fast multiplanar imaging in artifact-prone regions, such as the posterior fossa and the inferior frontal and temporal lobes. Diffusion imaging can be performed on conventional systems with strengths of 1.5 T that do not have echo-planar imaging capabilities.

Acute Disease↗

Enlargement of human cerebral ischemic lesion volumes measured by diffusion-weighted magnetic resonance imaging.

We aimed to determine the frequency and time course of the enlargement of ischemic cerebral lesions following human stroke and to study the effect of the state of perfusion on lesion enlargement. Acute lesion volumes were measured on diffusion-weighted magnetic resonance images and compared with lesion volumes measured on T2-weighted images at 7 days or later. Forty-four measurements were performed between 2 and 53 hours after stroke onset in 28 patients. Thirteen patients also had magnetic resonance perfusion imaging performed. In 12 (43%) of 28 patients the initial lesion volume increased by 20% or more. The number of studies showing enlargement of the ischemic lesion volume ranged from 12 (43%) of 28 at or after 2 hours to 10 (38%) of 26 at or after 6 hours, 5 (33%) of 15 at or after 24 hours, and 2 (33%) of 6 at or after 48 hours. In 7 of the 10 patients in whom the hypoperfusion volume acutely exceeded the volume of the abnormality on diffusion-weighted images, lesion volume increased by 20% or more. This study provided evidence that substantial enlargement of human cerebral ischemic lesion volumes can occur beyond the first 6, 12, or 24 hours after onset. A mismatch acutely between the region of hypoperfusion (larger) and the region of diffusion abnormality (smaller) may be predictive of ischemic lesion enlargement.

Adult↗

Ischemic lesion volumes in acute stroke by diffusion-weighted magnetic resonance imaging correlate with clinical outcome.

Diffusion-weighted magnetic resonance imaging detects ischemic injury within minutes after onset, and has been used to demonstrate drug efficacy in animal models of stroke. In 50 patients diagnosed with acute ischemic stroke (<24-hour duration) within the middle cerebral artery territory, lesion volume was measured by diffusion-weighted imaging. Thirty-four patients also had volumes measured by T2-weighted imaging chronically (median time, 7.5 weeks; mean, 15.9 weeks). Clinical severity was measured by the National Institutes of Health Stroke Scale Score and the Barthel index. Acute lesion volumes correlated with the acute stroke scale score (r = 0.56), the chronic stroke scale score (r = 0.63), and chronic lesion volumes (r = 0.84). Chronic volumes correlated with the chronic stroke scale score (r = 0.86) and the Barthel index (r = -0.60). When only cortically based lesions were considered, the correlations relating acute lesion volume measured by diffusion-weighted imaging (r = 0.61) and chronic lesion volume measured by T2-weighted imaging (r = 0.90) to the chronic stroke scale score were higher. These results provide evidence that lesion volumes determined by diffusion-weighted imaging acutely may be predictive of clinical severity and outcome, and may support a role for diffusion-weighted imaging in the assessment of acute stroke therapies in clinical trials.

Adult↗

Sensitivity and specificity of 99mTc-HMPAO SPECT cerebral perfusion measurements during the first 48 hours for the localization of cerebral infarction.

BACKGROUND AND PURPOSE: There is no routinely used method for imaging the location of the extent and severity of cerebral tissue perfusion changes during the first hours of ischemic stroke, the period during which therapeutic intervention is most likely to be successful. Cerebral perfusion measurements with single-photon emission CT (SPECT) may potentially provide this information rapidly and noninvasively. In this study, the sensitivity and specificity of 99mTc-hexamethylpropyleneamine oxime (HMPAO) SPECT cerebral perfusion measurements during the first 48 hours of cerebral ischemia for the localization of cerebral infarction were determined. METHODS: One hundred and four patients with acute ischemic stroke underwent 99mTc-HMPAO SPECT and CT scanning during the first 48 hours. In each patient, the location of the SPECT perfusion abnormality was compared with the location of infarction on a second brain CT acquired at a mean of 8 days after stroke. RESULTS: During the first 48 hours of ischemic stroke, the sensitivity of 99mTc-HMPAO SPECT in locating the site of infarction was 79% (110/139), and the specificity was 95% (362/381). SPECT was more sensitive in the localization of the vascular territory of cortical infarction (sensitivity, 93%) than pure subcortical infarcts (sensitivity, 47%). During the first 48 hours, SPECT was significantly more sensitive than brain CT (sensitivity of brain CT during the first 48 hours, 35%; P < .001, Mann-Whitney U test). CONCLUSIONS: HMPAO SPECT measurement provides a widely available and practical technique of locating cerebral ischemia acutely and demonstrates high sensitivity and specificity within the first 48 hours for the localization of the vascular territory of cerebral infarction. It is most sensitive for cortical ischemia but is limited by its resolution in the subcortex, particularly of white matter perfusion changes.

Aged↗

Changes in cerebral tissue perfusion during the first 48 hours of ischaemic stroke: relation to clinical outcome.

BACKGROUND: One major therapeutic strategy to minimise the extent of infarction after ischaemic stroke is to improve early reperfusion using thrombolytic agents. However, reperfusion may be hazardous and the period during which reperfusion may have a beneficial effect on tissue and clinical outcome is not known. METHODS: Fifty three patients were studied with serial cerebral perfusion (99mTcHMPAO SPECT) during the first 48 hours of ischaemic stroke to determine if changes in tissue perfusion during this time were prognostically significant. Single and multiple linear regression non-parametric analyses were used to include other factors during the same period which may influence outcome. RESULTS: In univariate analysis age, neurological score at admission, SPECT perfusion defect size in the first 24 hours, and percentage change in cerebral tissue perfusion at 24-48 hours (all P < 0.01) correlated significantly with the Barthel score at three months. In multiple linear regression analysis only age (P < 0.01) and percentage change in cerebral tissue perfusion at 24-48 hours (P < 0.01) provided independent prognostic information at three months. CONCLUSIONS: Changes in cerebral tissue perfusion during the first 48 hours of ischaemic stroke are significant outcome predictors and therapeutic effort aimed at increasing perfusion during this period seem to be justified.

Aged↗

Streptokinase increases luxury perfusion after stroke.

BACKGROUND AND PURPOSE: Recent acute stroke trials have reported that intravenous streptokinase is associated with an increased risk of adverse outcomes. We aimed to study the effect of streptokinase on the nature of reperfusion and the relation between reperfusion and clinical outcome. METHODS: We studied 24 patients in the Australian Streptokinase Trial with acute middle cerebral cortical infarction using 99mTc-hexamethylpropyleneamine oxime single-photon emission CT. Eleven of the 24 patients were scanned before therapy and again 24 hours later. The remaining 13 were scanned once either before therapy (1 patient) or after therapy (12 patients). All patients had outcome scans after 3 months. Infarct hypoperfusion was measured with a validated volumetric technique. Neurological impairment and functional outcome were assessed with the Canadian Neurological Scale and the Barthel Index, respectively. RESULTS: Fifteen patients received streptokinase and 9 received placebo. There was no difference in early reperfusion between streptokinase and placebo. However, streptokinase was associated with a greater amount of nonnutritional reperfusion than was placebo (P = .04). This luxury perfusion was associated with poor functional outcome (P = .02). CONCLUSIONS: This study suggests that streptokinase augments luxury perfusion after stroke. Luxury perfusion is associated with a worse outcome, which might be due in part to reperfusion injury.

Adult↗