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Background Patients presenting with large baseline infarctions are often excluded from mechanical thrombectomy (MT) due to uncertainty surrounding its effect on outcome. We hypothesized that computed tomography perfusion (CTP)- based selection may be predictive of functional outcome in low Alberta Stroke Program Early CT Score (ASPECTS) patients. Methods This was a double- center, retrospective analysis of patients presenting with ASPECTS≤5 who received multimodal admission CT imaging between May 2015 and June 2020. The predicted ischemic core (pCore) was defined as a reduction in cerebral blood flow (rCBF), while mismatch volume was defined using time to maximum (Tmax). The pCore perfusion mismatch ratio (CPMR) was also calculated. These parameters (pCore, mismatch volume, and CPMR), as well as a combined radiological score consisting of ASPECTS and collateral status (ASCO score), were tested in logistic regression and receiver operating characteristic (ROC) analyses. The primary outcome was favorable modified Rankin Scale (mRS) at discharge (≤3). Results A total of 113 patients met the inclusion criteria. The median ischemic core volume was 74.1 mL (IQR 43.8--121.8). The ASCO score was associated with favorable outcome at discharge (aOR 3.7, 95% CI 1.8 to 10.7, P=0.002), while no association was observed for the CTP parameters. A model including the ASCO score also had significantly higher area under the curve (AUC) values compared with the CTP- based model (0.88 vs 0.64, P=0.018). Conclusions The ASCO score was superior to the CTP- based model for the prediction of good functional outcome and could represent a quick, practical, and easily implemented method for the selection of low ASPECTS patients most likely benefit from MT. [ABSTRACT FROM AUTHOR]

Aim: In acute large vessel occlusions, endovascular therapy (EVT) achieves flow restoration in the majority of cases; however, EVT fails to achieve sufficient reperfusion in a substantial minority of patients. This study aimed to identify predictors of failed reperfusion. Methods: In this study 2211 patients from the German Stroke Registry who received EVT for anterior circulation stroke were retrospectively analyzed. Failure of reperfusion was defined as thrombolysis in cerebral infarction (TICI) grades 0/1/2a, and sufficient reperfusion as TICI 2b/3. In 1629 patients with complete datasets, associations between failure of reperfusion and baseline clinical data, comorbidities, location of occlusion, and procedural data were assessed with multiple logistic regression. Results: Failure of reperfusion occurred in 371 patients (16.8%) and was associated with the following locations of occlusion: cervical internal carotid artery (ICA, adjusted odds ratio, OR 2.01, 95% confidence interval, CI 1.08–3.69), intracranial ICA without carotid T occlusion (adjusted OR 1.79, 95% CI 1.05–2.98), and M2 segment (adjusted OR 1.86, 95% CI 1.21–2.84). Failed reperfusion was also associated with cervical ICA stenosis (>70% stenosis, adjusted OR 2.90, 95% CI 1.69–4.97), stroke of other determined etiology by TOAST (Trial of ORG 10172 in acute stroke treatment) criteria (e.g. nonatherosclerotic vasculopathies, adjusted OR 2.73, 95% CI 1.36–5.39), and treatment given outside the usual working hours (adjusted OR 1.41, 95% CI 1.07–1.86). Successful reperfusion was associated with higher Alberta stroke program early CT score (ASPECTS) on initial imaging (adjusted OR 0.85, 95% CI 0.79–0.92), treatment with the patient under general anesthesia (adjusted OR 0.72, 95% CI 0.54–0.96), and concomitant ICA stenting in patients with ICA stenosis (adjusted OR 0.20, 95% CI 0.11–0.38). Conclusion: Several factors are associated with failure of reperfusion, most notably occlusions of the proximal ICA and low ASPECTS on admission. Conversely, stent placement in the proximal ICA was associated with reperfusion success. [ABSTRACT FROM AUTHOR]

Purpose Mechanical thrombectomy (MT) is a highly effective therapy in patients with acute ischemic stroke due to large vessel occlusion (LVO). However, complete recanalization of the occluded vessel cannot be achieved in all patients, leading to poor clinical outcome. We analyzed the reasons for failed recanalization to help direct future improvements in therapy. Methods 648 consecutive stroke patients with LVO and an MT attempt were retrospectively analyzed for none or minimal recanalization, assessed according to the Thrombolysis in Cerebral infarction (TICI) score (0/1). Procedural parameters were evaluated in a standardized approach. Among other variables, number of retrieval attempts, devices, duration of the intervention, and rescue methods were analyzed. Results TICI 0/1 was observed in 72/648 patients (11%). in these patients, the thrombus could not be reached in 21% (n=15/72), was reached but not passed in 21% (n=15/72), and was reached and passed in 58% (n=42/72). Only a minor degree of initial recanalization was achieved in 19% (n=8/42) of patients with a reached occlusion during the course of the intervention. Furthermore, a higher number of passes with a single retriever device led to significant prolongation of the intervention. Therefore, major reasons for failed endovascular recanalization were difficult anatomical access and hard or resistant occlusions that might reflect hard thrombi or pre-existing atherosclerotic stenosis. Procedural complications such as dissection or perforation played a minor role. Conclusion in stroke patients with failed MT attempts, approximately 60% of occlusions can be passed. in such cases, rescue therapy might be considered to improve recanalization and clinical outcome. Further development of access devices might help in the remaining cases where the microcatheter could not be manipulated to or through the occlusion. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether oral administration of a standardised frankincense extract (SFE) is safe and reduces disease activity in patients with relapsing-remitting multiple sclerosis (RRMS).Methods: We performed an investigator-initiated, bicentric phase IIa, open-label, baseline-to-treatment pilot study with an oral SFE in patients with RRMS (NCT01450124). After a 4-month baseline observation phase, patients were treated for 8 months with an option to extend treatment for up to 36 months. The primary outcome measures were the number and volume of contrast-enhancing lesions (CEL) measured in MRI during the 4-month treatment period compared with the 4-month baseline period. Eighty patients were screened at two centres, 38 patients were included in the trial, 28 completed the 8-month treatment period and 18 of these participated in the extension period.Results: The SFE significantly reduced the median number of monthly CELs from 1.00 (IQR 0.75-3.38) to 0.50 (IQR 0.00-1.13; difference -0.625, 95% CI -1.25 to -0.50; P<0.0001) at months 5-8. We observed significantly less brain atrophy as assessed by parenchymal brain volume change (P=0.0081). Adverse events were generally mild (57.7%) or moderate (38.6%) and comprised mainly gastrointestinal symptoms and minor infections. Mechanistic studies showed a significant increase in regulatory CD4+ T cell markers and a significant decrease in interleukin-17A-producing CD8+ T cells indicating a distinct mechanism of action of the study drug.Interpretation: The oral SFE was safe, tolerated well and exhibited beneficial effects on RRMS disease activity warranting further investigation in a controlled phase IIb or III trial.Clinical Trial Registration: NCT01450124; Results. [ABSTRACT FROM AUTHOR]

Background and Purpose: In wake-up stroke, CT-based quantitative net water uptake (NWU) might serve as an alternative tool to MRI to guide intravenous thrombolysis with alteplase (IVT). An important complication after IVT is symptomatic intracerebral haemorrhage (sICH). As NWU directly implies ischaemic lesion progression, reflecting blood-brain barrier injury, we hypothesised that NWU predicts sICH in patients who had a ischaemic stroke undergoing thrombectomy with unknown onset., Methods: Consecutive analysis of all patients who had unknown onset anterior circulation ischaemic stroke who underwent CT at baseline and endovascular treatment between December 2016 and October 2020. Quantitative NWU was assessed on baseline CT. The primary endpoint was sICH. The association of NWU and other baseline parameters to sICH was investigated using inverse-probability weighting (IPW) analysis., Results: A total of 88 patients were included, of which 46 patients (52.3%) received IVT. The median NWU was 10.7% (IQR: 5.1-17.7). The proportion of patients with any haemorrhage and sICH were 35.2% and 13.6%. NWU at baseline was significantly higher in patients with sICH (19.1% vs 9.6%, p<0.0001) and the median Alberta Stroke Program Early CT Score (ASPECTS) was lower (5 vs 8, p<0.0001). Following IPW, there was no association between IVT and sICH in unadjusted analysis. However, after adjusting for ASPECTS and NWU, there was a significant association between IVT administration and sICH (14.6%, 95% CI: 3.3% to 25.6%, p<0.01)., Conclusion: In patients with ischaemic stroke with unknown onset, the combination of high NWU with IVT is directly linked to higher rates of sICH. Besides ASPECTS for evaluating the extent of the early infarct lesion, quantitative NWU could be used as an imaging biomarker to assess the degree of blood-brain barrier damage in order to predict the risk of sICH in patients with wake up stroke., Competing Interests: Competing interests: JF: German Ministry of Science and Education (BMBF), German Ministry of Economy and Innovation (BMWi), German Research Foundation (DFG), European Union (EU), Hamburgische Investitions- und Förderbank (IFB). GT: Grants by the European Union (Grant No. 278276 und 634809) and Deutsche Forschungsgemeinschaft (SFB 936, Projekt C2). AK: research collaboration agreement: Siemens Healthcare (company involved in CT/MRI distribution). All other authors reported no relationships with commercial firms whose products could be affected by the present study., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)