Significance: To study whether and to what extent neuronal stem cells can be reprogrammed postnatally and in the adult is of great importance because they hold the potential to treat neurological diseases for which there are no remedies so far. In the postnatal brain, neurogenesis is restricted to two brain regions: The subventricular zone (SVZ) gives rise to new neurons that preferentially develop a GABAergic phenotype, whereas in the dentate gyrus, glutamatergic neurons are produced. In this study, we took recourse to virus-mediated gene expression, and by introducing a key gene that is normally expressed in glutamatergic pyramidal neurons into SVZ-derived stem cells, we changed their GABAergic fate.

BACKGROUND AND PURPOSE: Information of collateral flow may help to determine eligibility for thrombectomy. Our aim was to identify CT perfusion–based surrogate parameters of good collateral status in acute anterior circulation ischemic stroke. MATERIALS AND METHODS: In this retrospective study, we assessed the collateral status of 214 patients who presented with acute ischemic stroke due to occlusion of the MCA M1 segment or the carotid terminus. Collaterals were assessed on dynamic CTA images analogous to the multiphase CTA score by Menon et al. CT perfusion parameters (time-to-maximum, relative CBF, hypoperfusion intensity ratio, and CBV-index) were assessed with RAPID software. The Spearman rank correlation and receiver operating characteristic analyses were performed to identify the parameters that correlate with collateral scores and good collateral supply (defined as a collateral score of ≥4). RESULTS: The Spearman rank correlation was highest for a relative CBF < 38% volume (ρ = −0.66, P < .001), followed by the hypoperfusion intensity ratio (ρ = −0.49, P < .001), CBV-index (ρ = 0.51, P < .001), and time-to-maximum > 8 seconds (ρ = −0.54, P < .001). Good collateral status was better identified by a relative CBF < 38% at a lesion size <27 mL (sensitivity of 75%, specificity of 80%) compared with a hypoperfusion intensity ratio of 0.8 (sensitivity of 60%, specificity of 78%), and time-to-maximum > 8 seconds (sensitivity of 68%, specificity of 76%). CONCLUSIONS: Automated CT perfusion analysis allows accurate identification of collateral status in acute ischemic stroke. A relative CBF < 38% may be a better perfusion-based indicator of good collateral supply compared with time-to-maximum, the hypoperfusion intensity ratio, and the CBV-index.

Background and purpose: Vasospasm is a common complication of endovascular therapy (EVT). There is a lack of understanding of risk factors for periprocedural vasospasm. Here, we aimed to identify factors associated with vasospasm in patients with acute ischemic stroke who undergo EVT. Methods: We conducted a retrospective single-center analysis of patients receiving EVT for anterior circulation vessel occlusion between January 2015 and December 2021. Patients were excluded if they showed signs of intracranial atherosclerotic disease (ICAD) or if they underwent intra-arterial thrombolysis. Study groups were defined as patients developing vasospasm during EVT (V+) and patients who did not (V−). The study groups were compared in univariable analysis. Multivariable regression models were developed to predict the patient’s risk for developing vasospasm based on pre-identified potential prognostic factors. The secondary endpoint was clinical outcome defined as the modified Rankin Scale (mRS) difference between pre-stroke mRS and discharge mRS (delta mRS) and likelihood of successful reperfusion (TICI 2b/3). Results: In total, 132/1768 patients (7.5%) developed vasospasm during EVT. Vasospasm was more likely to occur in EVT with multiple thrombectomy attempts and after several stent retriever maneuvers. Factors associated with developing vasospasm were younger age (OR = 0.967, 95% CI = 0.96–0.98) and lower pre-stroke mRS (OR = 0.759, 95% CI = 0.63–0.91). The prediction model incorporating patient age, pre-stroke mRS, stent retriever thrombectomy attempts, and total attempts as prognostic factors was found to predict vasospasm with good accuracy (AUC = 0.714, 95% CI = 0.709–0.720). V+ patients showed higher median (IQR) delta mRS (2 (1–4) vs 2 (1–3); p = 0.014). There was no difference in successful reperfusion (TICI 2b-3) between those with or without vasospasm. Conclusion: Vasospasm was a common complication in EVT affecting younger and previously healthy patients. Presence of vasospasm did not reduce the likelihood of successful reperfusion. As independent predictors, patient age, pre-stroke mRS, thrombectomy maneuvers, and stent retriever attempts predict the occurrence of vasospasm during EVT with good accuracy.

BACKGROUND: Optimal blood pressure (BP) management during endovascular stroke treatment is not well established. We studied whether an individualized approach for managing BP during endovascular stroke treatment gives a better clinical outcome than an approach with standardized systolic BP targets. METHODS: The INDIVIDUATE study (Individualized Blood Pressure Management During Endovascular Treatment of Acute Ischemic Stroke Under Procedural Sedation) is a randomized clinical trial with a prospective randomized open blinded end point (PROBE) design. Patients were recruited between October 1, 2020 and July 7, 2022 at a single center at a tertiary care university hospital. Patients were eligible, when they were suffering from acute ischemic stroke of the anterior circulation with occlusions of the internal carotid artery and middle cerebral artery and a National Institutes of Health Stroke Scale score of ≥8 receiving endovascular stroke treatment in procedural sedation. The intervention consists of an individualized BP management strategy, where preinterventional baseline systolic BP (SBP) values are used as intraprocedural BP targets. As a control, the standard treatment aims to maintain the intraprocedural SBP between 140 and 180 mm Hg. The main prespecified outcome is the proportion of favorable functional outcomes 90 days after stroke, defined as a modified Rankin Scale score of 0 to 2. RESULTS: Two hundred fifty patients were enrolled and included in the analysis, mean (SD) age was 77 (12) years, 142 (57%) patients were women, and mean (SD) National Institutes of Health Stroke Scale score on admission was 17 (5.2). In all, 123 (49%) patients were treated with individualized and 127 (51%) with standard BP management. Mean (SD) intraprocedural SBP was similar in the individualized versus standard BP management group (157 [19] versus 154 [18] mm Hg; P =0.16). The rate of favorable functional outcome after 3 months was not significantly different between the individualized versus the standard BP management group (25% versus 24%; adjusted odds ratio, 0.81 [95% CI, 0.41–1.61]; P =0.56). CONCLUSIONS: Among patients treated with endovascular stroke treatment due to an acute ischemic stroke of the anterior circulation, no significant difference was seen between the individualized BP management strategy, where intraprocedural SBP was targeted to baseline values, and the standardized regimen of targeting SBP between 140 and 180 mm Hg. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04578288.

Background: Optimal blood pressure (BP) management during endovascular stroke treatment in patients with large-vessel occlusion is not well established. We aimed to investigate associations of BP during different phases of endovascular therapy with reperfusion and functional outcome. Methods: We performed a post hoc analysis of a single-center prospective study that evaluated a new simplified procedural sedation standard during endovascular therapy (Keep Evaluating Protocol Simplification in Managing Periinterventional Light Sedation for Endovascular Stroke Treatment). BP during endovascular therapy in patients was managed according to protocol. Data from four different phases (baseline, pre-recanalization, post recanalization, and post intervention) were obtained, and mean BP values, as well as changes in BP between different phases and reductions in systolic BP (SBP) and mean arterial pressure (MAP) from baseline to pre-recanalization, were used as exposure variables. The main outcome was a modified Rankin Scale score of 0–2 three months after admission. Secondary outcomes were successful reperfusion and change in the National Institutes of Health Stroke Scale score after 24 h. Multivariable linear and logistic regression models were used for statistical analysis. Results: Functional outcomes were analyzed in 139 patients with successful reperfusion (defined as thrombolysis in cerebral infarction grade 2b–3). The mean (standard deviation) age was 76 (10.9) years, the mean (standard deviation) National Institutes of Health Stroke Scale score was 14.3 (7.5), and 70 (43.5%) patients had a left-sided vessel occlusion. Favorable functional outcome (modified Rankin Scale score 0–2) was less likely with every 10-mm Hg increase in baseline (odds ratio [OR] 0.76, P = 0.04) and pre-recanalization (OR 0.65, P = 0.011) SBP. This was also found for baseline (OR 0.76, P = 0.05) and pre-recanalization MAP (OR 0.66, P = 0.03). The maximum Youden index in a receiver operating characteristics analysis revealed an SBP of 163 mm Hg and MAP of 117 mm Hg as discriminatory thresholds during the pre-recanalization phase to predict functional outcome. Conclusions: In our protocol-based setting, intraprocedural pre-recanalization BP reductions during endovascular therapy were not associated with functional outcome. However, higher intraprocedural pre-recanalization SBP and MAP were associated with worse functional outcome. Prospective randomized controlled studies are needed to determine whether BP is a feasible treatment target for the modification of outcomes.

Background: Optimal blood pressure is not well established during endovascular therapy of acute ischemic stroke. Applying standardized blood pressure target values for every stroke patient might be a suboptimal approach. Aim: To assess whether an individualized intraprocedural blood pressure management with individualized blood pressure target ranges might pose a better strategy for the outcome of the patients than standardized blood pressure targets. Sample size: Randomization of 250 patients 1:1 to receive either standard or individualized blood pressure management approach. Methods and design: We conduct an explorative single-center randomized controlled trial with a PROBE (parallel-group, open-label randomized controlled trial with blinded endpoint evaluation) design. In the control group, intraprocedural systolic blood pressure target range is 140–180 mmHg. The intervention group is the individualized approach, which is maintaining the intraprocedural systolic blood pressure at the level on presentation (±10 mmHg). Study outcomes: The primary endpoint is the modified Rankin scale assessed 90 days +/− 2 weeks after stroke onset, dichotomized by 0–2 (favorable outcome) to 3–6 (unfavorable outcome). Secondary endpoints include early neurological improvement, infarction size, and systemic physiology monitor parameters. Discussion: An individualized approach for blood pressure management during thrombectomy could lead to a better outcome for stroke patients. The trial is registered at clinicaltrials.gov as ‘Individualized Blood Pressure Management During Endovascular Stroke Treatment (INDIVIDUATE)’ under NCT04578288.