It remains unclear if principal components of the local cerebral stroke immune response can be reliably and reproducibly observed in patients with acute large-vessel-occlusion (LVO) stroke. We prospectively studied a large independent cohort of n = 318 consecutive LVO stroke patients undergoing mechanical thrombectomy during which cerebral blood samples from within the occluded anterior circulation and systemic control samples from the ipsilateral cervical internal carotid artery were obtained. An extensive protocol was applied to homogenize the patient cohort and to standardize the procedural steps of endovascular sample collection, sample processing, and laboratory analyses. N = 58 patients met all inclusion criteria. (1) Mean total leukocyte counts were significantly higher within the occluded ischemic cerebral vasculature (I) vs. intraindividual systemic controls (S): +9.6%, I: 8114/µL ± 529 vs. S: 7406/µL ± 468, p = 0.0125. (2) This increase was driven by neutrophils: +12.1%, I: 7197/µL ± 510 vs. S: 6420/µL ± 438, p = 0.0022. Leukocyte influx was associated with (3) reduced retrograde collateral flow (R2 = 0.09696, p = 0.0373) and (4) greater infarct extent (R2 = 0.08382, p = 0.032). Despite LVO, leukocytes invade the occluded territory via retrograde collateral pathways early during ischemia, likely compromising cerebral hemodynamics and tissue integrity. This inflammatory response can be reliably observed in human stroke by harvesting immune cells from the occluded cerebral vascular compartment.

BackgroundEvidence of the consequences of different prehospital pathways before mechanical thrombectomy (MT) in large vessel occlusion stroke is inconclusive. The aim of this study was to investigate the infarct extent and progression before and after MT in directly admitted (mothership) versus transferred (drip and ship) patients using the Alberta Stroke Program Early CT Score (ASPECTS).MethodsASPECTS of 535 consecutive large vessel occlusion stroke patients eligible for MT between 2015 to 2019 were retrospectively analyzed for differences in the extent of baseline, post-referral, and post-recanalization infarction between the mothership and drip and ship pathways. Time intervals and transport distances of both pathways were analyzed. Multiple linear regression was used to examine the association between infarct progression (baseline to post-recanalization ASPECTS decline), patient characteristics, and logistic key figures.ResultsASPECTS declined during transfer (9 (8–10) vs 7 (6-9), p<0.0001), resulting in lower ASPECTS at stroke center presentation (mothership 9 (7–10) vs drip and ship 7 (6–9), p<0.0001) and on follow-up imaging (mothership 7 (4–8) vs drip and ship 6 (3–7), p=0.001) compared with mothership patients. Infarct progression was significantly higher in transferred patients (points lost, mothership 2 (0–3) vs drip and ship 3 (2–6), p<0.0001). After multivariable adjustment, only interfacility transfer, preinterventional clinical stroke severity, the degree of angiographic recanalization, and the duration of the thrombectomy procedure remained predictors of infarct progression (R2=0.209, p<0.0001).ConclusionsInfarct progression and postinterventional infarct extent, as assessed by ASPECTS, varied between the drip and ship and mothership pathway, leading to more pronounced infarction in transferred patients. ASPECTS may serve as a radiological measure to monitor the benefit or harm of different prehospital pathways for MT.

Temporary hypercapnia has been shown to increase cerebral blood flow (CBF) and might be used as a therapeutical tool in patients with severe subarachnoid hemorrhage (SAH). It was the aim of this study was to investigate the optimum duration of hypercapnia. This point is assumed to be the time at which buffer systems become active, cause an adaptation to changes of the arterial partial pressure of carbon dioxide (PaCO2) and annihilate a possible therapeutic effect. In this prospective interventional study in a neurosurgical ICU the arterial partial pressure of carbon dioxide (PaCO2) was increased to a target range of 55 mmHg for 120 min by modification of the respiratory minute volume (RMV) one time a day between day 4 and 14 in 12 mechanically ventilated poor-grade SAH-patients. Arterial blood gases were measured every 15 min. CBF and brain tissue oxygen saturation (StiO2) were the primary and secondary end points. Intracranial pressure (ICP) was controlled by an external ventricular drainage. Under continuous hypercapnia (PaCO2 of 53.17 ± 5.07), CBF was significantly elevated between 15 and 120 min after the start of hypercapnia. During the course of the trial intervention, cardiac output also increased significantly. To assess the direct effect of hypercapnia on brain perfusion, the increase of CBF was corrected by the parallel increase of cardiac output. The maximum direct CBF enhancing effect of hypercapnia of 32% was noted at 45 min after the start of hypercapnia. Thereafter, the CBF enhancing slowly declined. No relevant adverse effects were observed. CBF and StiO2 reproducibly increased by controlled hypercapnia in all patients. After 45 min, the curve of CBF enhancement showed an inflection point when corrected by cardiac output. It is concluded that 45 min might be the optimum duration for a therapeutic use and may provide an optimal balance between the benefits of hypercapnia and risks of a negative rebound effect after return to normal ventilation parameters.Trial registration: The study was approved by the institutional ethics committee (AZ 230/14) and registered at ClinicalTrials.gov (Trial-ID: NCT01799525). Registered 01/01/2015.

Background It is unknown whether technological advancement of stent-retriever devices influences typical observational indicators of safety or effectiveness. Methods Observational retrospective study of APERIO® (AP) vs. new generation APERIO® Hybrid (APH) (Acandis®, Pforzheim, Germany) stent-retriever device (01/2019–09/2020) for mechanical thrombectomy (MT) in large vessel occlusion (LVO) stroke. Primary effectiveness endpoint was successful recanalization eTICI (expanded Thrombolysis In Cerebral Ischemia) ≥ 2b67, primary safety endpoint was occurrence of hemorrhagic complications after MT. Secondary outcome measures were time from groin puncture to first pass and successful reperfusion, and the total number of passes needed to achieve the final recanalization result. Results A total of 298 patients with LVO stroke who were treated by MT matched the inclusion criteria: 148 patients (49.7%) treated with AP vs. 150 patients (50.3%) treated with new generation APH. Successful recanalization was not statistically different between both groups: 75.7% for AP vs. 79.3% for APH; p = 0.450. Postinterventional hemorrhagic complications and particularly subarachnoid hemorrhage as the entity possibly associated with stent-retriever device type was significantly less frequent in the group treated with the APH: 29.7% for AP and 16.0% for APH; p = 0.005; however, rates of symptomatic hemorrhage with clinical deterioration and in domo mortality were not statistically different. Neither the median number of stent-retriever passages needed to achieve final recanalization, time from groin puncture to first pass, time from groin puncture to final recanalization nor the number of cases in which successful recanalization could only be achieved by using a different stent-retriever as bail-out device differed between both groups. Conclusion In the specific example of the APERIO® stent-retriever device, we observed that further technological developments of the new generation device were not associated with disadvantages with respect to typical observational indicators of safety or effectiveness.

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BackgroundAim of this study was to investigate the time point at which the cerebral blood flow (CBF) enhancing effect of controlled hypercapnia in patients with severe aneurysmal subarachnoid hemorrhage (SAH) starts to extenuate. This point is assumed to be the time at which buffer systems become active and annihilate a possible therapeutic effect. MethodsIn this prospective interventional study in a neurosurgical ICU the arterial partial pressure of carbon dioxide (PaCO2) was increased to a target range of 50 - 55 mmHg for 120 minutes by modification of the respiratory minute volume (RMV) one time a day between day 4 and 14 in 12 mechanically ventilated poor-grade SAH-patients. Arterial blood gases were measured every 15 minutes. CBF and brain tissue oxygen saturation (StiO2) were the primary and secondary end points. Intracranial pressure (ICP) was controlled by an external ventricular drainage. ResultsUnder continuous hypercapnia (PaCO2 of 53.17 ± 5.07), CBF was significantly elevated between 15 and 120 minutes after the start of hypercapnia. During the course of the trial intervention, cardiac output also increased significantly. To assess the direct effect of hypercapnia on brain perfusion, the increase of CBF was corrected by the parallel increase of cardiac output. The maximum direct CBF enhancing effect of hypercapnia of 31% was noted at 45 minutes after the start of hypercapnia. Thereafter, the CBF enhancing slowly declined. No relevant adverse effects were observed. Conclusion CBF and StiO2 reproducibly increased by controlled hypercapnia in all patients. After 45 minutes, the curve of CBF enhancement showed an inflection point when corrected by cardiac output. Temporary hypercapnia of 45 minutes is, thus, likely to be the optimum duration for a therapeutic use and for a controlled comparative trial. Longer intervals bear the risk of a negative rebound effect after return to normal ventilation parameters and may be counterproductive inducing ischemia in a state of critical perfusion after SAH. Trial registrationThe study was approved by the institutional ethics committee (AZ 230/14) and registered at ClinicalTrials.gov (Trial-ID: NCT01799525). Registered 01 January 2015. Retrospectively registered.