[Show abstract][Hide abstract] ABSTRACT: Collateral vessel status is strongly associated with clinical outcome in ischemic stroke but can be challenging to assess. The aim of this study was to develop a tomography perfusion source imaging-based assessment of collateral vessel status.
Consecutive patients with ischemic stroke who received intravenous thrombolysis or intra-arterial reperfusion therapy after CTP were retrospectively analyzed. In those with middle cerebral artery or internal carotid artery occlusion, CT perfusion source imaging was used to identify the relative filling time delay between the normal MCA Sylvian branches and those in the affected hemisphere. Receiver operating characteristic analysis and logistic regression were used to assess the association of the relative filling time delay with the 24-hour Alberta Stroke Program Early CT Score based on noncontrast CT and the 90-day modified Rankin Scale score.
There were 217 patients treated in 2009-2011 who had CTP data, of whom 60 had MCA or ICA occlusion and 55 had 90-day mRS data. The intraclass correlation coefficient for relative filling time delay was 0.95. Relative filling time delay was correlated with 24-hour ASPECTS (Spearman ρ = -0.674; P < .001) and 90-day mRS score (ρ = 0.516, P < .01). Increased relative filling time delay was associated with poor radiologic outcome (ASPECTS, 0-7) (area under the curve = 0.79, P < .001) and poor functional outcome (mRS score, 3-6) (area under the curve = 0.77, P = .001). In multivariate logistic regression, the association of longer relative filling time delay with poor outcome remained significant, independent of age, sex, and baseline National Institutes of Health Stroke Scale score.
Relative filling time delay is a useful independent predictor of clinical outcome after ischemic stroke.
American Journal of Neuroradiology 04/2014; · 3.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background and PurposeIn acute ischemic stroke perfusion/diffusion-weighted image, mismatch using magnetic resonance imaging approximates the ischemic penumbra. For early time windows, mismatch salvage improves clinical outcomes, but uncertainty exists at later time epochs. We hypothesized that (a) mismatch may exist up to 48 h; (b) the proportion of mismatch salvage is time independent; and (c) when salvaged, it improves clinical outcomes. Methods
Magnetic resonance imaging was performed within 48 h of ischemic stroke. Perfusion-weighted image was defined by relative Tmax two-second delay. Perfusion/diffusion-weighted image mismatch was the perfusion-weighted image not overlapped by the diffusion-weighted image when coregistered. Infarct volume and disability (modified Rankin Score) were assessed at three-months. Mismatch salvage was the region not overlapped by final infarction. Favorable outcome was defined as modified Rankin Score 0–1. ResultsSixty-six patients were studied [mean age 69·9 years (standard deviation 13·1), initial median National Institute of Health Stroke Scale 9·0 (interquartile range 6·0, 18·3)]. There was no relationship between time of stroke onset and the proportion of mismatch salvaged (P = 0·73). Age (adjusted odds ratio = 0·92, 95% confidence interval 0·86–0·98, P = 0·01), initial National Institute of Health Stroke Scale (adjusted odds ratio = 0·80, 95% confidence interval 0·70–0·92, P < 0·01), mismatch volume (adjusted odds ratio = 0·98, 95% confidence interval 0·968–0·1, P = 0·05), and percentage of mismatch salvage (adjusted odds ratio = 1·04, 95% confidence interval 0·99–1·07, P = 0·05) were independently associated with favorable outcome. Conclusion
Using coregistered perfusion/diffusion-weighted image criteria, mismatch persists up to 48 h post stroke. For the whole group, the proportion of mismatch salvage remains independent of time and, although the effect is small, its salvage is independently associated with improved clinical outcomes at three-months. Larger sample sizes are needed to determine the time limit for mismatch salvage.
International Journal of Stroke 04/2014; · 2.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND AND PURPOSE:Intracerebral hemorrhage growth independently predicts disability and death. We hypothesized that noncontrast quantitative CT densitometry reflects active bleeding and improves predictive models of growth.MATERIALS AND METHODS:We analyzed 81 of the 96 available baseline CT scans obtained <3 hours post-ICH from the placebo arm of the phase IIb trial of recombinant factor VIIa. Fifteen scans could not be analyzed for technical reasons, but baseline characteristics were not statistically significantly different. Hounsfield unit histograms for each ICH were generated. Analyzed qCTD parameters included the following: mean, SD, coefficient of variation, skewness (distribution asymmetry), and kurtosis ("peakedness" versus "flatness"). These densitometry parameters were examined in statistical models accounting for baseline volume and time-to-scan.RESULTS:The coefficient of variation of the ICH attenuation was the most significant individual predictor of hematoma growth (adjusted R(2) = 0.107, P = .002), superior to BV (adjusted R(2) = 0.08, P = .006) or TTS (adjusted R(2) = 0.03, P = .05). The most significant combined model incorporated coefficient of variation, BV, and TTS (adjusted R(2) = 0.202, P = .009 for coefficient of variation) compared with BV and TTS alone (adjusted R(2) = 0.115, P < .05). qCTD increased the number of growth predictions within ±1 mL of actual 24-hour growth by up to 47%.CONCLUSIONS:Heterogeneous ICH attenuation on hyperacute (<3 hours) CT imaging is predictive of subsequent hematoma expansion and may reflect an active bleeding process. Further studies are required to determine whether qCTD can be incorporated into standard imaging protocols for predicting ICH growth.
American Journal of Neuroradiology 01/2013; · 3.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Thrombolysis trials have recruited few patients aged ≥80 years, which has led to uncertainty about the likely risk-to-benefit profile in the elderly. Leukoaraiosis (LA) has been associated with hemorrhagic transformation (HT) and increases with advanced age. We tested whether there were any independent associations between age, LA and HT. Consecutive patients treated with intravenous (IV) tissue plasminogen activator (tPA) were identified from a prospective database. LA on baseline CT scans was assessed by two independent raters using the modified Van Swieten Score (mVSS) (maximum score 8, severe >4). HT was assessed on routine 24 hour to 48 hour CT /MRI scans using the European Cooperative Acute Stroke Study criteria for hemorrhagic infarct (HI) or parenchymal hematoma (PH) and judged symptomatic by the treating neurologist as per Safe Implementation of Thrombolysis in Stroke criteria. There were 206 patients treated with IV tPA (mean age: 71.0 years; range: 24-92 years), of whom 65/206 (32%) were aged ≥80 years. Overall, HT occurred in 41/206 patients (20%), HI in 31, PH1 in four (one symptomatic) and PH2 in six (three symptomatic). Age was not associated with HT (any HT: odds ratio [OR]=1.01; 95% confidence interval [CI]=0.5-2.08; p=0.99; PH: OR=0.53; 95% CI=0.12-2.3; p=0.51). There was one patient with PH1 and one patient with PH2 in 65 patients ≥80 years, both asymptomatic. LA was present in 112/208 (54%), and severe in 16.5%. LA increased with age (p<0.001) but was not associated with PH (any LA: OR=0.83; 95% CI=0.25-2.8; p=0.99; severe LA: OR=0.54, 95% CI=0.09-3.5; p=0.99). Age ≥80 years or LA did not increase the risk of HT (including PH) after thrombolysis, although LA increased with age. Neither factor should exclude otherwise eligible patients from tPA treatment.
Journal of Clinical Neuroscience 03/2012; 19(3):360-3. · 1.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The use of diffusion-weighted imaging (DWI) to define irreversibly damaged infarct core is challenged by data suggesting potential partial reversal of DWI abnormalities. However, previous studies have not considered infarct involution. We investigated the prevalence of DWI lesion reversal in the EPITHET Trial.
EPITHET randomized patients 3-6 hours from onset of acute ischemic stroke to tissue plasminogen activator (tPA) or placebo. Pretreatment DWI and day 90 T2-weighted images were coregistered. Apparent reversal of the acute ischemic lesion was defined as DWI lesion not incorporated into the final infarct. Voxels of CSF at follow-up were subtracted from regions of apparent DWI lesion reversal to adjust for infarct atrophy. All cases were visually cross-checked to exclude volume loss and coregistration inaccuracies.
In 60 patients, apparent reversal involved a median 46% of the baseline DWI lesion (median volume 4.9 mL, interquartile range 2.6-9.5 mL) and was associated with less severe baseline hypoperfusion (p < 0.001). Apparent reversal was increased by reperfusion, regardless of the severity of baseline hypoperfusion (p = 0.02). However, the median volume of apparent reversal was reduced by 45% when CSF voxels were subtracted (2.7 mL, interquartile range 1.6-6.2 mL, p < 0.001). Perfusion-diffusion mismatch classification only rarely altered after adjusting the baseline DWI volume for apparent reversal. Visual comparison of acute DWI to subacute DWI or day 90 T2 identified minor regions of true DWI lesion reversal in only 6 of 93 patients.
True DWI lesion reversal is uncommon in ischemic stroke patients. The volume of apparent lesion reversal is small and would rarely affect treatment decisions based on perfusion-diffusion mismatch.
[Show abstract][Hide abstract] ABSTRACT: Previous data have suggested that diabetes and hyperglycemia predict poor outcome following stroke. We studied the prognostic impact of diabetes and admission blood glucose in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET).
EPITHET was a prospective randomized placebo-controlled trial of intravenous tissue plasminogen activator (tPA) in the 3- to 6-hour time window. A preexisting diagnosis of diabetes was noted and baseline serum glucose was measured.
Intravenous tPA attenuated infarct growth in non-diabetics, but not in diabetics (p = 0.029). In the tPA treatment group, admission blood glucose was higher among patients with poor functional outcome (p = 0.002).
Diabetes and hyperglycemia attenuate the effects of tPA on infarct evolution. Future thrombolytic trials should consider randomizing patients by subgroups based on diabetic status and serum glucose levels.
[Show abstract][Hide abstract] ABSTRACT: The mismatch between perfusion weighted images (PWI) and diffusion weighted images (DWI) using MR is increasingly being applied in patient selection for therapeutic trials. Two approaches to the calculation of the mismatch volume exist--the commonly used volumetric and the more precise co-registration method, the latter of which considers lesion topography. That there are differences in the mismatch volume analysed by each method and that these are time dependent was hypothesised.
Patients within 48 h of ischaemic stroke onset had baseline MR PWI/DWI mismatch and T2 outcome volumes at 3 months. Volumetric mismatch volume was defined as PWI minus DWI lesion. Co-registration mismatch volume was defined as the PWI defect lesion not overlapped by the co-registered DWI lesion.
72 patients of median age 74.0 years were studied. Median baseline MR was at 5.9 h (IQR 3.0, 20.4 h) after stroke onset. Consistent underestimation of the mismatch volume occurred using the volumetric method (volumetric median 9.3 ml, IQR 0, 63 ml; co-registration median 20.1 ml, IQR 3.2, 69.8 ml; p<0.0001). This difference increased with time from stroke onset (p = 0.006).
Volumetric analysis consistently underestimates the PWI/DWI mismatch volume compared with the more precise co-registration method. This effect increases with time.
Journal of neurology, neurosurgery, and psychiatry 05/2009; 80(9):991-6. · 4.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We systematically reviewed the literature to explore gender issues in acute stroke thrombolysis. The literature is inconsistent regarding the influence of gender on the timing of presentation to hospital, decision-making and utilization of acute thrombolysis among ischemic stroke patients, and hence any reported gender bias may be site-specific. Without treatment with thrombolysis, female stroke patients have a poorer clinical outcome compared to their male counterparts. Although some studies show that women have better clinical outcomes than men following intravenous thrombolysis, no gender difference is seen in others. Post-hoc analyses of relatively small studies show higher recanalisation rates in women than men following intravenous thrombolysis, and no gender difference in recanalisation rates following intra-arterial thrombolysis. Future thrombolytic trials should consider the effects of gender on both surrogate and clinical outcomes.
Journal of Clinical Neuroscience 03/2009; 16(4):501-4. · 1.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of thrombolytic therapy after acute ischemic stroke is salvage of the ischemic penumbra. Several imaging techniques have been used to identify the penumbra in patients who may benefit from reperfusion beyond the currently narrow 3-hour time-window for thrombolysis. We discuss the advantages and disadvantages of positron emission tomography (PET), single photon emission computed tomography (SPECT), MRI and CT scans. We comment on concepts of clinical-imaging mismatch models and we explore the implications for clinical trials.
Journal of Clinical Neuroscience 01/2009; 16(2):178-87. · 1.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although volume of intracerebral hemorrhage (ICH) is a predictor of mortality, it is unknown whether subsequent hematoma growth further increases the risk of death or poor functional outcome.
To determine if hematoma growth independently predicts poor outcome, the authors performed an individual meta-analysis of patients with spontaneous ICH who had CT within 3 hours of onset and 24-hour follow-up. Placebo patients were pooled from three trials investigating dosing, safety, and efficacy of rFVIIa (n = 115), and 103 patients from the Cincinnati study (total 218). Other baseline factors included age, gender, blood glucose, blood pressure, Glasgow Coma Score (GCS), intraventricular hemorrhage (IVH), and location.
Overall, 72.9% of patients exhibited some degree of hematoma growth. Percentage hematoma growth (hazard ratio [HR] 1.05 per 10% increase [95% CI: 1.03, 1.08; p < 0.0001]), initial ICH volume (HR 1.01 per mL [95% CI: 1.00, 1.02; p = 0.003]), GCS (HR 0.88 [95% CI: 0.81, 0.96; p = 0.003]), and IVH (HR 2.23 [95% CI: 1.25, 3.98; p = 0.007]) were all associated with increased mortality. Percentage growth (cumulative OR 0.84 [95% CI: 0.75, 0.92; p < 0.0001]), initial ICH volume (cumulative OR 0.94 [95% CI: 0.91, 0.97; p < 0.0001]), GCS (cumulative OR 1.46 [95% CI: 1.21, 1.82; p < 0.0001]), and age (cumulative OR 0.95 [95% CI: 0.92, 0.98; p = 0.0009]) predicted outcome modified Rankin Scale. Gender, location, blood glucose, and blood pressure did not predict outcomes.
Hematoma growth is an independent determinant of both mortality and functional outcome after intracerebral hemorrhage. Attenuation of growth is an important therapeutic strategy.