Circadian rhythm of ischaemic core progression in human stroke.

INTRODUCTION: Experimental stroke studies suggest an influence of the time of day of stroke onset on infarct progression. Whether this holds true after human stroke is unknown, but would have implications for the design of randomised controlled trials, especially those on neuroprotection. METHODS: We pooled data from 583 patients with anterior large-vessel occlusion stroke from three prospectively recruited cohorts. Ischaemic core and penumbra volumes were determined with CT perfusion using automated thresholds. Core growth was calculated as the ratio of core volume and onset-to-imaging time. To determine circadian rhythmicity, we applied multivariable linear and sinusoidal regression analysis adjusting for potential baseline confounders. RESULTS: Patients with symptom onset at night showed larger ischaemic core volumes on admission compared with patients with onset during the day (median, 40.2 mL vs 33.8 mL), also in adjusted analyses (p=0.008). Sinusoidal analysis indicated a peak of core volumes with onset at 11pm. Core growth was faster at night compared with day onset (adjusted p=0.01), especially for shorter onset-to-imaging times. In contrast, penumbra volumes did not change across the 24-hour cycle. DISCUSSION: These results suggest that human infarct progression varies across the 24-hour cycle with potential implications for the design and interpretation of neuroprotection trials.

CT after interhospital transfer in acute ischemic stroke: Imaging findings and impact of prior intravenous contrast administration.

Objectives: Large vessel occlusion (LVO) stroke patients routinely undergo interhospital transfer to endovascular thrombectomy capable centers. Imaging is often repeated with residual intravenous (IV) iodine contrast at post-transfer assessment. We determined imaging findings and the impact of residual contrast on secondary imaging. Anterior circulation LVO stroke patients were selected out of a consecutive cohort. Directly admitted patients were contrast naïve, and transferred patients had previously received IV iodine contrast for stroke assessment at the referring hospital. Two independent readers rated the visibility of residual contrast on non-contrast computed tomography (CT) after transfer and assessed the hyperdense vessel sign. Multivariate linear regression analysis was used to investigate the association of the Alberta Stroke Program Early CT score (ASPECTS) with prior contrast administration, time from symptom onset (TFSO), and CTP ischemic core volume in both directly admitted and transferred patients. Results: We included 161 patients, with 62 (39%) transferred and 99 (62%) directly admitted patients. Compared between these groups, transferred patients had a longer TFSO-to-imaging at our institution (median: 212 vs. 75 min, p < 0.001) and lower ASPECTS (median: 8 vs. 9, p < 0.001). Regression analysis presented an independent association of ASPECTS with prior contrast administration (ß = -0.25, p = 0.004) but not with TFSO (ß = -0.03, p = 0.65). Intergroup comparison between transferred and directly admitted patients pointed toward a stronger association between ASPECTS and CTP ischemic core volume in transferred patients (ß = -0.39 vs. ß = -0.58, p = 0.06). Detectability of the hyperdense vessel sign was substantially lower after transfer (66 vs. 10%, p < 0.001). Conclusion: Imaging alterations due to residual IV contrast are frequent in clinical practice and render the hyperdense vessel sign largely indetectable. Larger studies are needed to clarify the influence on the association between ASPECTS and ischemic core.

Computed Tomography Perfusion Deficit Volumes Predict Functional Outcome in Patients With Basilar Artery Occlusion.

Background and Purpose: Basilar artery occlusion is associated with high morbidity and mortality. Optimal imaging and treatment strategy are still controversial and prognosis estimation challenging. We, therefore, aimed to determine the predictive value of computed tomography perfusion (CTP) parameters for functional outcome in patients with basilar artery occlusion in the context of endovascular treatment. Methods: Patients with basilar artery occlusion who underwent endovascular treatment were selected from a prospectively acquired cohort. Ischemic changes were assessed with the posterior-circulation Acute Stroke Prognosis Early Computed Tomography Score on noncontrast computed tomography, computed tomography angiography (CTA) source images, and CTP maps. Basilar artery on CTA score, posterior-circulation CTA score, and posterior-circulation collateral score were evaluated on CTA. Perfusion deficit volumes were quantified on CTP maps. Good functional outcome was defined as modified Rankin Scale score ≤3 at 90 days. Statistical analysis included binary logistic regressions and receiver operating characteristics analyses. Results: Among 49 patients who matched the inclusion criteria, 24 (49.0%) achieved a good outcome. In univariate analysis, age, National Institutes of Health Stroke Scale score on admission, posterior cerebral artery involvement, absence of or hypoplastic posterior communicating arteries, basilar artery on CTA score, posterior-circulation Acute Stroke Prognosis Early Computed Tomography Score, and perfusion deficit volumes on all CTP parameter maps presented significant association with functional outcome (P<0.05). In multivariate analyses, Basilar artery on CTA score, posterior-circulation Acute Stroke Prognosis Early Computed Tomography Score (odds ratio range, 1.31­2.10 [95% CI, 1.00­7.24]), and perfusion deficit volumes on all CTP maps (odds ratio range, 0.77­0.98 [95% CI, 0.63­1.00]) remained as independent outcome predictors. Cerebral blood flow deficit volume yielded the best performance for the classification of good clinical outcome with an area under the curve of 0.92 (95% CI, 0.84­0.99). Age and admission National Institutes of Health Stroke Scale had lower discriminatory power (area under the curve, <0.7). Conclusions: CTP imaging parameters contain prognostic information for functional outcome in patients with stroke due to basilar artery occlusion and may identify patients with higher risk of disability at an early stage of hospitalization.

Decomposing Acute Symptom Severity in Large Vessel Occlusion Stroke: Association With Multiparametric CT Imaging and Clinical Parameters.

Background and Purpose: Acute ischemic stroke of the anterior circulation due to large vessel occlusion (LVO) is a multifactorial process, which causes neurologic symptoms of different degree. Our aim was to examine the impact of neuromorphologic and vascular correlates as well as clinical factors on acute symptom severity in LVO stroke. Methods: We selected LVO stroke patients with known onset time from a consecutive cohort which underwent multiparametric CT including non-contrast CT, CT angiography and CT perfusion (CTP) before thrombectomy. Software-based quantification was used to calculate CTP total ischemic and ischemic core volume. Symptom severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) upon admission. Multivariable regression analysis was performed to determine independent associations of admission NIHSS with imaging and clinical parameters. Receiver operating characteristics (ROC) analyses were used to examine performance of imaging parameters to classify symptom severity. Results: We included 142 patients. Linear and ordinal regression analyses for NIHSS and NIHSS severity groups identified significant associations for total ischemic volume [ß = 0.31, p = 0.01; Odds ratio (OR) = 1.11, 95%-confidence-interval (CI): 1.02-1.19], clot burden score (ß = -0.28, p = 0.01; OR = 0.76, 95%-CI: 0.64-0.90) and age (ß = 0.17, p = 0.04). No association was found for ischemic core volume, stroke side, collaterals and time from onset. Stroke topography according to the Alberta Stroke Program CT Score template did not display significant influence after correction for multiple comparisons. AUC for classification of the NIHSS threshold ≥6 by total ischemic volume was 0.81 (p < 0.001). Conclusions: We determined total ischemic volume, clot burden and age as relevant drivers for baseline NIHSS in acute LVO stroke. This suggests that not only mere volume but also degree of occlusion influences symptom severity. Use of imaging parameters as surrogate for baseline NIHSS reached limited performance underlining the need for combined clinical and imaging assessment in acute stroke management.

Performance of Automated Attenuation Measurements at Identifying Large Vessel Occlusion Stroke on CT Angiography.

PURPOSE: Computed tomography angiography (CTA) is routinely used to detect large-vessel occlusion (LVO) in patients with suspected acute ischemic stroke; however, visual analysis is time consuming and prone to error. To evaluate solutions to support imaging triage, we tested performance of automated analysis of CTA source images (CTASI) at identifying patients with LVO. METHODS: Stroke patients with LVO were selected from a prospectively acquired cohort. A control group was selected from consecutive patients with clinically suspected stroke without signs of ischemia on CT perfusion (CTP) or infarct on follow-up. Software-based automated segmentation and Hounsfield unit (HU) measurements were performed on CTASI for all regions of the Alberta Stroke Program Early CT score (ASPECTS). We derived different parameters from raw measurements and analyzed their performance to identify patients with LVO using receiver operating characteristic curve analysis. RESULTS: The retrospective analysis included 145 patients, 79 patients with LVO stroke and 66 patients without stroke. The parameters hemispheric asymmetry ratio (AR), ratio between highest and lowest regional AR and M2-territory AR produced area under the curve (AUC) values from 0.95-0.97 (all p < 0.001) for detecting presence of LVO in the total population. Resulting sensitivity (sens)/specificity (spec) defined by the Youden index were 0.87/0.97-0.99. Maximum sens/spec defined by the specificity threshold ≥0.70 were 0.91-0.96/0.77-0.83. Performance in a small number of patients with isolated M2 occlusion was lower (AUC: 0.72-0.85). CONCLUSION: Automated attenuation measurements on CTASI identify proximal LVO stroke patients with high sensitivity and specificity. This technique can aid in accurate and timely patient selection for thrombectomy, especially in primary stroke centers without CTP capacity.

Diaschisis revisited: quantitative evaluation of thalamic hypoperfusion in anterior circulation stroke.

PURPOSE: Ipsilateral thalamic diaschisis (ITD) refers to the phenomenon of thalamic hypoperfusion or hypometabolism due to a distant cerebral injury. To further investigate the characteristics and spectrum of ITD, we analyzed quantitative measurements of thalamic hypoperfusion in acute anterior circulation stroke. METHODS: We selected consecutive patients with large-vessel occlusion (LVO) anterior circulation stroke and available CT perfusion (CTP) examination on admission who underwent endovascular thrombectomy. Thalamic perfusion parameters on CTP were tested between ipsi- and contralesional thalamus and ischemic territory. Values were compared with thresholds from CTP analysis software. Associations of thalamic perfusion parameters with acute imaging and clinical data were determined in uni- and multivariate logistic regression analyses. RESULTS: Ninety-nine patients were included. All perfusion parameters indicated significant non-ischemic hypoperfusion of the thalamus, not reaching the levels of ischemia in the middle cerebral artery territory due to LVO (all p < 0.002). Multiple perfusion parameters exhibited significant association with ischemic lesion extent (relative cerebral blood flow [CBF]: ß =  - 0.23, p = 0.022; Δtime to drain: ß = 0.33, p < 0.001; ΔTmax: ß =  - 0.36, p < 0.001) and involvement of the Lentiform Nucleus (Δmean transit time: ß = 0.64, p = 0.04; Δtime to drain: ß = 0.81, p = 0.01; ΔTmax: ß =  - 0.82, p = 0.01). Symptom severity on admission exhibited minor significant association with reduction of thalamic CBF in uncorrected analysis (Odds ratio: 0.05, p = 0.049), but short- and long-term outcomes were unaffected by perfusion status. ITD reached guideline-based software-threshold levels in only one patient. CONCLUSIONS: ITD in acute stroke is a non-binary phenomenon affected by lesion extent and involvement of the lentiform nucleus. We found uncorrected association of ITD with early clinical presentation, but no association with short- or long-term outcome was evident. Relevant misclassification of ITD by guideline-based CTP software was not indicated, which needs further dedicated testing.