Medicine (RMH) - Research Publications
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ItemToo Good to Treat? Ischemic Stroke Patients with Small Computed Tomography Perfusion Lesions May Not Benefit from Thrombolysis(WILEY-BLACKWELL, 2016-08)OBJECTIVE: Although commonly used in clinical practice, there remains much uncertainty about whether perfusion computed tomography (CTP) should be used to select stroke patients for acute reperfusion therapy. In this study, we tested the hypothesis that a small acute perfusion lesion predicts good clinical outcome regardless of thrombolysis administration. METHODS: We used a prospectively collected cohort of acute ischemic stroke patients being assessed for treatment with IV-alteplase, who had CTP before a treatment decision. Volumetric CTP was retrospectively analyded to identify patients with a small perfusion lesion (<15ml in volume). The primary analysis was excellent 3-month outcome in patients with a small perfusion lesion who were treated with alteplase compared to those who were not treated. RESULTS: Of 1526 patients, 366 had a perfusion lesion <15ml and were clinically eligible for alteplase (212 being treated and 154 not treated). Median acute National Institutes of Health Stroke Scale score was 8 in each group. Of the 366 patients with a small perfusion lesion, 227 (62%) were modified Rankin Scale (mRS) 0 to 1 at day 90. Alteplase-treated patients were less likely to achieve 90-day mRS 0 to 1 (57%) than untreated patients (69%; relative risk [RR] = 0.83; 95% confidence interval [CI], 0.71-0.97; p = 0.022) and did not have different rates of mRS 0 to 2 (72% treated patients vs 77% untreated; RR, 0.93; 95% CI, 0.82-1.95; p = 0.23). INTERPRETATION: This large observational cohort suggests that a portion of ischemic stroke patients clinically eligible for alteplase therapy with a small perfusion lesion have a good natural history and may not benefit from treatment. Ann Neurol 2016;80:286-293.
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ItemThe blood pressure paradox in acute ischemic stroke(WILEY, 2019-03)OBJECTIVE: To explore the association of poststroke baseline blood pressure with cerebral collateral flow and functional outcome in acute ischemic patients with large vessel occlusion/stenosis. METHODS: Patients identified with large vessel occlusion/stenosis with baseline multimodal computed tomography, follow-up imaging, and complete clinical profiles were included. A 90-day modified Rankin Scale of 0-1 was defined as an excellent functional outcome. Cerebral collateral flow was quantified by the volume ratio of tissue within the delay time >3 seconds perfusion lesion with severely delayed contrast transit (delay time >3 seconds/delay time >6 seconds). RESULTS: There were 306 patients included in this study. With every increase of 10 mmHg in baseline systolic blood pressure, the odds of achieving an excellent functional outcome decreased by 12% in multivariate analysis (odds ratio = 0.88, p = 0.048). Conversely, increased baseline blood pressure was associated with better collateral flow. In subgroup analysis of patients with major reperfusion, higher blood pressure was associated with decreased infarct growth and a better clinical outcome, and vice versa in patients without reperfusion. INTERPRETATION: Higher baseline blood pressure in acute ischemic stroke patients with large vessel occlusion/stenosis was associated with better collateral flow. However, for patients without reperfusion, higher baseline blood pressure was associated with increased infarct growth, leading to an unfavorable clinical outcome. The relationship between blood pressure and outcomes is highly dependent on reperfusion, and active blood pressure-lowering treatment may be inappropriate in acute ischemic stroke patients prior to reperfusion treatment. ANN NEUROL 2019;85:331-339.
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ItemWhite Matter Degeneration after Ischemic Stroke: A Longitudinal Diffusion Tensor Imaging Study(WILEY, 2019-01)BACKGROUND AND PURPOSE: Degeneration of gray matter and subcortical structures after ischemic stroke has been well described. However, little is known about white matter degeneration after stroke. It is unclear whether white matter degeneration occurs throughout the whole brain, or whether patterns of degeneration occur more in specific brain areas. METHODS: We prospectively collected National Institutes of Health Stroke Scale (NIHSS) scores and diffusion tensor imaging (DTI) in patients with acute ischemic stroke within the first week after onset (baseline), and at 1 and 3 months. DTI was processed to produce maps of fractional anisotropy, apparent diffusion coefficients, and axial and radial diffusivity. DTI parameters in specified regions-of-interest corresponding to items on the NIHSS were calculated and changes over time were assessed using linear mixed-effect modeling. RESULTS: Seventeen patients were included in the study. Mean age (SD) was 71 (11.7) years, and median (IQR) baseline NIHSS 9 (5-13.3). Changes over time were observed in both visual cortices, contralesional primary motor cortex, premotor cortex, and superior temporal gyrus (P < .05). Changes in the ipsilesional motor cortex and inferior parietal lobule were only seen in patients with scores on the respective NIHSS-items (P < .05). No significant changes in global white matter diffusivity parameters were identified (P > .05). CONCLUSION: White matter changes after stroke may be localized rather than a global phenomenon.
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ItemGrowth Hormone Deficiency Is Frequent After Recent Stroke(FRONTIERS MEDIA SA, 2018-09-06)Introduction: The incidence of pituitary dysfunction after severe ischemic stroke is unknown, however given the increasing attention to pituitary dysfunction after neurological injuries such as traumatic brain injury, this may represent a novel area of research in stroke. Methods: We perform an arginine and human growth hormone releasing hormone challenge on ischemic stroke patients within a week of symptom onset. Results: Over the study period, 13 patients were successfully tested within a week of stroke (baseline NIHSS 10, range 7-16). Overall, 9(69%) patients had a poor response, with 7(54%) of these patients meeting the criteria for had human growth hormone deficiency. Other measures of pituitary function were within normal ranges. Conclusion: After major ischemic stroke, low GH levels are common and may play a role in stroke recovery.
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ItemReview of Stroke Thrombolytics(KOREAN STROKE SOC, 2013-05)The cornerstone of acute ischemic stroke treatment relies on rapid clearance of an offending thrombus in the cerebrovascular system. There are various drugs and different methods of assessment to select patients more likely to respond to treatment. Current clinical guidelines recommend the administration of intravenous alteplase (following a brain noncontract CT to exclude hemorrhage) within 4.5 hours of stroke onset. Because of the short therapeutic time window, the risk of hemorrhage, and relatively limited efficacy of alteplase for large clot burden, research is ongoing to find more effective and safer reperfusion therapy, as well as focussing on refinement of patient selection for acute reperfusion treatment. Studies using advanced imaging (incorporating perfusion CT or diffusion/perfusion MRI) may allow us to use thrombolytics, or possibly endovascular therapy, in an extended time window. Recent clinical trials have suggested that Tenecteplase, used in conjunction with advanced imaging selection, resulted in more effective reperfusion than alteplase, which translated into increased clinical benefit. Studies using Desmoteplase have suggested its potential benefit in a sub-group of patients with large artery occlusion and salveageable tissue, in an extended time window. Other ways to improve acute reperfusion approaches are being actively explored, including endovascular therapy, and the enhancement of thrombolysis by ultrasound insonation of the clot (sono-thrombolysis).
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ItemPerfusion computed tomography to assist decision making for stroke thrombolysis(OXFORD UNIV PRESS, 2015-07-01)The use of perfusion imaging to guide selection of patients for stroke thrombolysis remains controversial because of lack of supportive phase three clinical trial evidence. We aimed to measure the outcomes for patients treated with intravenous recombinant tissue plasminogen activator (rtPA) at a comprehensive stroke care facility where perfusion computed tomography was routinely used for thrombolysis eligibility decision assistance. Our overall hypothesis was that patients with 'target' mismatch on perfusion computed tomography would have improved outcomes with rtPA. This was a prospective cohort study of consecutive ischaemic stroke patients who fulfilled standard clinical/non-contrast computed tomography eligibility criteria for treatment with intravenous rtPA, but for whom perfusion computed tomography was used to guide the final treatment decision. The 'real-time' perfusion computed tomography assessments were qualitative; a large perfusion computed tomography ischaemic core, or lack of significant perfusion lesion-core mismatch were considered relative exclusion criteria for thrombolysis. Specific volumetric perfusion computed tomography criteria were not used for the treatment decision. The primary analysis compared 3-month modified Rankin Scale in treated versus untreated patients after 'off-line' (post-treatment) quantitative volumetric perfusion computed tomography eligibility assessment based on presence or absence of 'target' perfusion lesion-core mismatch (mismatch ratio >1.8 and volume >15 ml, core <70 ml). In a second analysis, we compared outcomes of the perfusion computed tomography-selected rtPA-treated patients to an Australian historical cohort of non-contrast computed tomography-selected rtPA-treated patients. Of 635 patients with acute ischaemic stroke eligible for rtPA by standard criteria, thrombolysis was given to 366 patients, with 269 excluded based on visual real-time perfusion computed tomography assessment. After off-line quantitative perfusion computed tomography classification: 253 treated patients and 83 untreated patients had 'target' mismatch, 56 treated and 31 untreated patients had a large ischaemic core, and 57 treated and 155 untreated patients had no target mismatch. In the primary analysis, only in the target mismatch subgroup did rtPA-treated patients have significantly better outcomes (odds ratio for 3-month, modified Rankin Scale 0-2 = 13.8, P < 0.001). With respect to the perfusion computed tomography selected rtPA-treated patients (n = 366) versus the clinical/non-contrast computed tomography selected rtPA-treated patients (n = 396), the perfusion computed tomography selected group had higher adjusted odds of excellent outcome (modified Rankin Scale 0-1 odds ratio 1.59, P = 0.009) and lower mortality (odds ratio 0.56, P = 0.021). Although based on observational data sets, our analyses provide support for the hypothesis that perfusion computed tomography improves the identification of patients likely to respond to thrombolysis, and also those in whom natural history may be difficult to modify with treatment.
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ItemVisibility of CT Early Ischemic Change Is Significantly Associated with Time from Stroke Onset to Baseline Scan beyond the First 3 Hours of Stroke Onset(KOREAN STROKE SOC, 2017-09)BACKGROUND AND PURPOSE: Non-contrast brain computed tomography (NCCT) remains the most common imaging modality employed to select patients for thrombolytic therapy in acute ischemic stroke. The current study used the Alberta Stroke Program Early CT Score (ASPECTS) to identify early ischemic changes on brain NCCT imaging with the aim to investigate whether a relationship exists between time from symptoms onset to NCCT with the presence of early ischaemic change quantified by ASPECTS. METHODS: We studied 1,329 ischemic stroke patients who had NCCT within 8 hours of stroke onset. Patients were assessed to see if they had any ASPECTS lesion and if the rate of patients with a lesion increased with time using logistic regression. RESULTS: 30% patients had an ASPECTS <10 within the first 3 hours from symptom onset. Within the first 3 hours, the odds for a CT change (ASPECTS <10) per minute of time was 1.00 with 95% confidence interval (CI) (0.99 to 1.00) (P=0.266). After 3 hours, there was a significant increase in odds of ASPECTS <10 with increasing time. The odds of being ASPECTS positive increased 1% (odds ratio=1.01) per 1 minute of time with 95% CI (1.00 to 1.01) (P=0.002). CONCLUSIONS: We have identified that prior to first 3 hours of stroke there was no effect of time on odds of CT ischemic change; after the first 3 hours of stroke the odds increased with increasing time to CT scan. The occurrence of early ischemic change may be a marker of time from stroke onset rather than severity.
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ItemEvaluation of hyperacute infarct volume using ASPECTS and brain CT perfusion core volume(LIPPINCOTT WILLIAMS & WILKINS, 2017-06-13)OBJECTIVE: To compare the accuracy of Alberta Stroke Program Early Computed Tomography Score (ASPECTS) and CT perfusion to detect established infarction in acute anterior circulation stroke. METHODS: We performed an observational study in 59 acute anterior circulation ischemic stroke patients who underwent brain noncontrast CT, CT perfusion, and MRI within 100 minutes from CT imaging. ASPECTS scores were calculated by 4 blinded vascular neurologists. The accuracy of ASPECTS and CT perfusion core volume to detect an acute MRI diffusion lesion of ≥70 mL was evaluated using receiver operating characteristics analysis and optimum cutoff values were calculated using Youden J. RESULTS: Median ASPECTS score was 8 (interquartile range [IQR] 5-9). Median CT perfusion core volume was 22 mL (IQR 10.4-71.9). Median MRI diffusion lesion volume was 24.5 mL (IQR 10-63.9). No significant difference was found between the accuracy of CT perfusion and ASPECTS (c statistic 0.95 vs 0.87, p value for difference = 0.17). The optimum ASPECTS cutoff score to detect a diffusion-weighted imaging lesion ≥70 mL was <7 (sensitivity 0.74, specificity 0.86, Youden J = 0.60) and the optimum CT perfusion core volume cutoff was ≥50 mL (sensitivity 0.86, specificity 0.97, Youden J = 0.84). The CT perfusion core lesion covered a median of 100% (IQR 86%-100%) of the acute MRI lesion volume (Pearson R = 0.88; R2 = 0.77). CONCLUSIONS: We found no significant difference between the accuracy of CT perfusion and ASPECTS to predict hyperacute MRI lesion volume in ischemic stroke.
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ItemAssociation of Cortical Vein Filling with Clot Location and Clinical Outcomes in Acute Ischaemic Stroke Patients(NATURE PUBLISHING GROUP, 2016-12-05)Delay in cortical vein filling during the late-venous phase (delayed-LCVF) is characterized by opacification of cerebral veins despite contrast clearance from contralateral veins on dynamic computed tomography angiography (dCTA) in acute ischemic stroke (AIS) patients. The aim of the study was to investigate the associations of delayed-LCVF with clot location, reperfusion status at 24 hours, and 90-days functional outcome in AIS patients who received reperfusion therapy. A prospective cohort of AIS patients treated with intravenous thrombolysis was studied. Groupwise comparison, univariate, and multivariate regression analyses were used to study the association of delayed-LCVF with clot location and clinical outcomes. Of 93 patients (mean age = 72 ± 12 years) with hemispheric AIS included in the study, 46 (49%) demonstrated delayed-LCVF. Patients with delayed-LCVF demonstrated a significantly higher proportion of proximal occlusion (72% vs 13%, P =< 0.0001), and poor reperfusion at 24 hours (41% vs 11%, P = 0.001). The proportion of poor functional outcome at 90 days was not significantly different (22/56 (48%) vs 17/61 (36%), P = 0.297). The appearance of delayed-LCVF on baseline dCTA may be a surrogate for large vessel occlusion, and an early marker for poor 24-hour angiographic reperfusion.
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ItemTissue Is More Important than Time in Stroke Patients Being Assessed for Thrombolysis(FRONTIERS MEDIA SA, 2018-02-05)AIM: The relative prognostic importance of modern imaging profiles compared with standard clinical characteristics is uncertain in acute stroke patients. In this study, we aimed to compare baseline multimodal CT imaging measures with known clinical predictors of patient outcome at 3 months [modified Rankin scale (mRS)]. METHODS: We collected baseline, 24 h, and day 90 clinical and imaging data from acute ischemic stroke patients being assessed for thrombolytic therapy between 2010 and 2015 at a single center as part of a retrospective analysis. RESULTS: 561 patients presenting within 4.5 h of ischemic stroke onset who were eligible for thrombolysis based on standard clinical criteria were assessed. Acute infarct core volume on CTP was the strongest univariate predictor of patient outcome (mRS 0-2, R2 0.497, p < 0.001), followed by collateral grade (mRS 0-2, R2 0.281, p < 0.001). The strongest baseline clinical predictor of outcome was National Institutes of Health Stroke Scale (NIHSS) (mRS 0-2, R2 = 0.203, p < 0.001). Time to treatment (mRS 0-2, R2 0.096, p = 0.01) and age (mRS 0-2, R2 0.027, p = 0.013) were relatively weak univariate baseline clinical predictors of 3-month outcome. In multivariate analysis, acute infarct core volume and collateral grade were the only significant baseline predictors of 3-month disability (both p < 0.001). CONCLUSION: In patients assessed for thrombolysis by combined clinical and multimodal CT criteria within 4.5 h of onset, the size of the CTP infarct core and collateral grade on multimodal CT were highly predictive of patient outcome. Standard clinical variables, including time to treatment and NIHSS, were not as strongly predictive as multimodal CT variables.