Mild fever as a catalyst for consumption of the ischaemic penumbra despite endovascular reperfusion.

Cerebrovascular ischaemia is potentiated by hyperthermia, and even mild temperature elevation has proved detrimental to ischaemic brain. Infarction progression following endovascular reperfusion relates to multiple patient-specific and procedural variables; however, the potential influence of mild systemic temperature fluctuations is not fully understood. This study aims to assess the relationship between systemic temperatures in the early aftermath of acute ischaemic stroke and the loss of at-risk penumbral tissues, hypothesizing consumption of the ischaemic penumbra as a function of systemic temperatures, irrespective of reperfusion status. A cross-sectional, retrospective evaluation of a single-institution, prospectively collected endovascular therapy registry was conducted. Patients with anterior circulation, large vessel occlusion acute ischaemic stroke who underwent initial CT perfusion, and in whom at least four-hourly systemic temperatures were recorded beginning from presentation and until the time of final imaging outcome were included. Initial CT perfusion core and penumbra volumes and final MRI infarction volumes were computed. Systemic temperature indices including temperature maxima were recorded, and pre-defined temperature thresholds varying between 37°C and 38°C were examined in unadjusted and adjusted regression models which included glucose, collateral status, reperfusion status, CT perfusion-to-reperfusion delay, general anaesthesia and antipyretic exposure. The primary outcome was the relative consumption of the penumbra, reflecting normalized growth of the at-risk tissue volume ≥10%. The final study population comprised 126 acute ischaemic stroke subjects (mean 63 ± 14.5 years, 63% women). The primary outcome of penumbra consumption ≥10% occurred in 51 (40.1%) subjects. No significant differences in baseline characteristics were present between groups, with the exception of presentation glucose (118 ± 26.6 without versus 143.1 ± 61.6 with penumbra consumption, P = 0.009). Significant differences in the likelihood of penumbra consumption relating to systemic temperature maxima were observed [37°C (interquartile range 36.5 - 37.5°C) without versus 37.5°C (interquartile range 36.8 - 38.2°C) with penumbra consumption, P = 0.001]. An increased likelihood of penumbra consumption was observed for temperature maxima in unadjusted (odds ratio 3.57, 95% confidence interval 1.65 - 7.75; P = 0.001) and adjusted (odds ratio 3.06, 95% confidence interval 1.33 - 7.06; P = 0.009) regression models. Significant differences in median penumbra consumption were present at a pre-defined temperature maxima threshold of 37.5°C [4.8 ml (interquartile range 0 - 11.5 ml) versus 21.1 ml (0 - 44.7 ml) for subjects not reaching or reaching the threshold, respectively, P = 0.007]. Mild fever may promote loss of the ischaemic penumbra irrespective of reperfusion, potentially influencing successful salvage of at-risk tissue volumes following acute ischaemic stroke.

Clinical and Imaging Outcomes of Endovascular Therapy in Patients with Acute Large Vessel Occlusion Stroke and Mild Clinical Symptoms.

BACKGROUND: The minimal stroke severity justifying endovascular intervention remains elusive. However, a significant proportion of patients presenting with large vessel occlusion stroke (LVOS) and mild symptoms go untreated and face poor outcomes. We aimed to evaluate the clinical outcomes of patients presenting with LVOS and low symptom scores (National Institutes of Health Stroke Scale [NIHSS] score ≤8) undergoing endovascular therapy (ET). METHODS: We performed a retrospective analysis of a prospectively collected ET database between September 2010 and March 2016. Endovascularly treated patients with LVOS and a baseline NIHSS score ≤8 were included. Baseline patient characteristics, procedural details, and outcome parameters were collected. Efficacy outcomes were the rate of good outcome (90-day modified Rankin Scale score 0-2) and of successful reperfusion (modified Treatment in Cerebral Infarction [mTICI] score 2b-3). Safety was assessed by the rate of parenchymal hematoma (parenchymal hematoma type 1 [PH-1] and parenchymal hematoma type 2 [PH-2]) and 90-day mortality. Logistic regression was used to identify predictors of good clinical outcomes. RESULTS: A total of 935 patients were considered; 72 patients with an NIHSS score ≤8 were included. Median [IQR] age was 61.5 years [56.2-73.0]; 39 patients (54%) were men. Mean (SD) baseline NIHSS score, computed tomography perfusion core volume, and ASPECTS were 6.3 (1.5), 7.5 mL (16.1), and 8.5 (1.3), respectively. Twenty-eight patients (39%) received intravenous tissue plasminogen activator. Occlusions locations were as follows: 29 (40%) proximal MCA-M1, 20 (28%) MCA-M2, 6 (8%) ICA terminus, and 9 (13%) vertebrobasilar. Tandem occlusion was documented in 7 patients (10%). Sixty-seven patients (93%) achieved successful reperfusion (mTICI score 2b-3); 52 (72%) had good 90-day outcomes. Mean final infarct volume was 32.2 ± 59.9 mL. Parenchymal hematoma occurred in 4 patients (6%). Ninety-day mortality was 10% (n = 7). Logistic regression showed that only successful reperfusion (OR 27.7, 95% CI 1.1-655.5, p = 0.04) was an independent predictor of good outcomes. CONCLUSION: Our findings demonstrate that ET is safe and feasible for LVOS patients presenting with mild clinical syndromes. Future controlled studies are warranted.

Selection Paradigms for Large Vessel Occlusion Acute Ischemic Stroke Endovascular Therapy.

BACKGROUND: Optimal patient selection methods for thrombectomy in large vessel occlusion stroke (LVOS) are yet to be established. We sought to evaluate the ability of different selection paradigms to predict favorable outcomes. METHODS: Review of a prospectively collected database of endovascular patients with anterior circulation LVOS, adequate CT perfusion (CTP), National Institutes of Health Stroke Scale (NIHSS) ≥10 from September 2010 to March 2016. Patients were retrospectively assessed for thrombectomy eligibility by 4 mismatch criteria: Perfusion-Imaging Mismatch (PIM): between CTP-derived perfusion defect and ischemic core volumes; Clinical-Core Mismatch (CCM): between age-adjusted NIHSS and CTP core; Clinical-ASPECTS Mismatch (CAM-1): between age-adjusted NIHSS and ASPECTS; Clinical-ASPECTS Mismatch (CAM-2): between NIHSS and ASPECTS. Outcome measures were inclusion rates for each paradigm and their ability to predict good outcomes (90-day modified Rankin Scale 0-2). RESULTS: Three hundred eighty-four patients qualified. CAM-2 and CCM had higher inclusion (89.3 and 82.3%) vs. CAM-1 (67.7%) and PIM (63.3%). Proportions of selected patients were statistically different except for PIM and CAM-1 (p = 0.19), with PIM having the highest disagreement. There were no differences in good outcome rates between PIM(+)/PIM(-) (52.2 vs. 48.5%; p = 0.51) and CAM-2(+)/CAM-2(-) (52.4 vs. 38.5%; p = 0.12). CCM(+) and CAM-1(+) had higher rates compared to nonselected counterparts (53.4 vs. 38.7%, p = 0.03; 56.6 vs. 38.6%; p = 0.002). The abilities of PIM, CCM, CAM-1, and CAM-2 to predict outcomes were similar according to the c-statistic, Akaike and Bayesian information criterion. CONCLUSIONS: For patients with NIHSS ≥10, PIM appears to disqualify more patients without improving outcomes. CCM may improve selection, combining a high inclusion rate with optimal outcome discrimination across (+) and (-) patients. Future studies are warranted.

Computed Tomographic Perfusion Selection and Clinical Outcomes After Endovascular Therapy in Large Vessel Occlusion Stroke.

BACKGROUND AND PURPOSE: Different imaging paradigms have been used to select patients for endovascular therapy in stroke. We sought to determine whether computed tomographic perfusion (CTP) selection improves endovascular therapy outcomes compared with noncontrast computed tomography alone. METHODS: Review of a prospectively collected registry of anterior circulation stroke patients undergoing stent-retriever thrombectomy at a tertiary care center between September 2010 and March 2016. Patients undergoing CTP were compared with those with noncontrast computed tomography alone. The primary outcome was the shift in the 90-day modified Rankin scale (mRS). RESULTS: A total of 602 patients were included. CTP-selected patients (n=365, 61%) were younger (P=0.02) and had fewer comorbidities. CTP selection (n=365, 61%) was associated with a favorable 90-day mRS shift (adjusted odds ratio [aOR]=1.49; 95% confidence interval [CI], 1.06-2.09; P=0.02), higher rates of good outcomes (90-day mRS score 0-2: 52.9% versus 40.4%; P=0.005), modified Thrombolysis in Cerebral Infarction-3 reperfusion (54.8% versus 40.1%; P<0.001), smaller final infarct volumes (24.7 mL [9.8-63.1 mL] versus 34.6 mL [13.1-88 mL]; P=0.017), and lower mortality (16.6% versus 26.8%; P=0.005). When matched on age, National Institutes of Health Stroke Scale (NIHSS) score, and glucose (n=424), CTP remained associated with a favorable 90-day mRS shift (P=0.016), lower mortality (P=0.02), and higher rates of reperfusion (P<0.001). CTP better predicted functional outcomes in patients presenting after 6 hours (as assessed by comparison of logistic regression models: Akaike information criterion: 199.35 versus 287.49 and Bayesian information criterion: 196.71 versus 283.27) and those with an Alberta Stroke Program Early Computed Tomography Score ≤7 (Akaike information criterion: 216.69 versus 334.96 and Bayesian information criterion: 213.6 versus 329.94). CONCLUSIONS: CTP selection is associated with a favorable mRS shift in patients undergoing stent-retriever thrombectomy. Future prospective studies are warranted.