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Background and purpose To investigate the reliability and accuracy of Alberta Stroke Program Early Computed Tomography Scores (ASPECTS) derived from flatpanel detector computed tomography pooled blood volume maps compared to non-contrast computed tomography and multidetector computed tomography perfusion cerebral blood volume maps. Methods ASPECTS from pooled blood volume maps were evaluated retrospectively by two experienced readers for 37 consecutive patients with acute middle cerebral artery (MCA) M1 occlusion who underwent flatpanel detector computed tomography perfusion imaging before mechanical thrombectomy between November 2016 and February 2019. For comparison with ASPECTS from non-contrast computed tomography and cerebral blood volume maps, a matched-pair analysis according to pre-stroke modified Rankin scale, age, stroke severity, site of occlusion, time from stroke onset to imaging and final modified thrombolysis in cerebral infarction (mTICI) was performed in a separate group of patients who underwent multimodal computed tomography prior to mechanical thrombectomy between June 2015 and February 2019. Follow-up ASPECTS were derived from either non-contrast computed tomography or from magnetic resonance imaging (in seven patients) one day after mechanical thrombectomy. Results Interrater agreement was best for non-contrast computed tomography ASPECTS (w-kappa = 0.74, vs. w-kappa = 0.63 for cerebral blood volume ASPECTS and w-kappa = 0.53 for pooled blood volume ASPECTS). Also, accuracy, defined as correlation between acute and follow-up ASPECTS, was best for non-contrast computed tomography ASPECTS (Spearman ρ = 0.86 (0.65–0.97), P Conclusion Non-contrast computed tomography ASPECTS outperformed both pooled blood volume ASPECTS and cerebral blood volume ASPECTS in accuracy and reliability. Importantly, relevant infarct overestimation was observed more often in pooled blood volume ASPECTS than cerebral blood volume ASPECTS, limiting its present clinical applicability for acute stroke imaging.

Purpose Unfavorable vascular anatomy can impede thrombectomy in patients with acute ischemic stroke. The aim of this study was to determine the prevalence of aortic arch types, aortic arch branching patterns and supra-aortic arterial tortuosity in stroke patients with large vessel occlusion. Methods Computed tomography (CT) and magnetic resonance (MR) images of all stroke patients in an institutional thrombectomy registry were retrospectively reviewed. Aortic arch types and branching patterns of all patients were determined. In patients with anterior circulation stroke, the prevalence of tortuosity (elongation, kinking or coiling) of the supra-aortic arteries of the affected side was additionally assessed. Results A total of 1705 aortic arches were evaluated. Frequency of aortic arch types I, II and III were 777 (45.6%), 585 (34.3%) and 340 (19.9%), respectively. In 1232 cases (72.3%), there was a normal branching pattern of the aortic arch. The brachiocephalic trunk and the left common carotid artery had a common origin in 258 cases (15.1%). In 209 cases (12.3%), the left common carotid artery arose from the brachiocephalic trunk. Of 1598 analyzed brachiocephalic trunks and/or common carotid arteries, 844 (52.8%) had no vessel tortuosity, 592 (37.0%) had elongation, 155 (9.7%) had kinking, and 7 (0.4%) had coiling. Of 1311 analyzed internal carotid arteries, 471 (35.9%) had no vessel tortuosity, 589 (44.9%) had elongation, 150 (11.4%) had kinking, and 101 (7.7%) had coiling. Conclusion With 20%, type III aortic arches are found in a relevant proportion of stroke patients eligible for mechanical thrombectomy. Nearly half of the stroke patients present with supra-aortic arterial tortuosity, mostly arterial elongation.

BACKGROUND AND PURPOSE Trimethylamine-N-oxide (TMAO) is a biomarker of the gut microbiome and correlates with the risk of cardiovascular diseases. However, conflicting data exist on the specific role of TMAO in ischaemic stroke patients. We aimed to analyze the time course of TMAO levels in stroke patients compared with controls. METHODS In this prospective, case-control study, patients suffering from ischaemic stroke (onset

International audience; BACKGROUND: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. METHODS: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0-1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0-2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4-6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. FINDINGS: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10-2·03]; p=0·011), with low heterogeneity across studies (I(2)=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05-1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06-2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4-6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52-1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03-4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [\textless1%], adjusted OR 5·58 [1·22-25·50]; p=0·024). INTERPRETATION: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death. FUNDING: None.

BACKGROUND Telemedical services can be used to complement on-site services when demand for specialists exceeds supply or when specialists are not evenly distributed across health systems. Using stroke as an example, this study aimed to explore how patients and staff experience telestroke cooperation in a stroke network in Germany. METHODS We conducted a qualitative multi-method and multi-centre study combining 32 non-participant observations at one hub and four spoke hospitals with 26 semi-structured interviews with hub and spoke staff as well as stroke patients and relatives. Observation protocols and interview transcripts were analysed to identify barriers and facilitators to telestroke cooperation from the perspectives of staff, patients and relatives. RESULTS In terms of barriers to telestroke cooperation, we found technological problems, providing the treatment for one patient from two sites, competing priorities between telestroke and in-house duties in the spoke hospitals, as well as difficulties in participating in the teleneurological examination via a videoconferencing system for older and disabled patients. In terms of facilitators, we found an overall very positive perception of telestroke provision by patients, good professional relationships within the network, and sharing of neurological expertise to be experienced as helpful for telestroke cooperation. CONCLUSIONS We recommend better integration of telemedical services into the care pathway, fostering relationships within the network, improved technological support and resources, and more emphasis within networks, in public awareness efforts as well as in academia on the evaluation of telemedical services from the perspectives of patients and relatives, especially older patients and patients with disabilities.

In patients with acute ischemic stroke, we aimed to investigate whether microvascular changes, as indexed by capillary transit time heterogeneity (CTH), contribute to the decline of the chance for favorable outcome over time and whether they are a predictor of an intracranial hemorrhage (ICH). We retrospectively calculated CTH maps for 131 consecutive patients with acute ischemic stroke due to large vessel occlusion of the anterior circulation who had a relevant MRI PWI-DWI mismatch and were treated with endovascular thrombectomy (ET). Multivariable logistic regressions were conducted with favorable outcome (mRS ≤ 2 after 3 months) and occurrence of an ICH as dependent variables and the volume of mildly elevated CTH as independent variable adjusted for age, successful recanalization, hypertension, diabetes, atrial fibrillation, NIHSS score on admission, DWI lesion volume, and symptom-onset-to-treatment time (OTT). A larger volume of mildly elevated CTH was a positive predictor of favorable outcome (OR 1.17; 1.03–1.33; p = 0.019) and a negative predictor of ICH (OR 0.83; 0.73–0.96; p = 0.009). As expected, successful recanalization (OR 5.54; 1.8–17; p = 0.003), low NIHSS on admission (OR 0.9; 0.82–1.00; p = 0.045), short OTT (OR 0.96; 0.94–0.99; p = 0.006), and low DWI volume (OR 0.68; 0.49–0.94; p = 0.021) were also predictors of favorable outcome, whereas other negative predictors of ICH were atrial fibrillation (OR 2.69; 1.10–6.57; p = 0.030), high NIHSS score on admission (OR 1.10 (1.01–1.19); p = 0.030), and large DWI volume (OR 1.51; 1.17–1.19; p = 0.002). An increased volume of mildly elevated CTH is a positive predictor of favorable outcome and a negative predictor for ICH in patients with acute ischemic stroke and mismatch undergoing ET. • The classification of potentially salvageable tissue and infarct core based on traditional net perfusion parameters (as Tmax or CBF) does not account for the microvascular distribution of blood. • However, the microvascular distribution of blood, as indexed by the capillary transit time heterogeneity (CTH), directly affects the availability of oxygen within the hypoperfused tissue and should therefore be respected in acute ischemic stroke imaging. • In our study, mildly elevated CTH is found to be a positive predictor for a favorable clinical outcome and a negative predictor for the occurrence of an intracranial hemorrhage in patients with acute ischemic stroke and homogenous mismatch who underwent ET.

Background: Transient ischemic attack (TIA) needs further diagnostic evaluation to prevent future ischemic stroke. However, prophylaxis can be harmful in elderly if the diagnosis is wrong. We aimed at characterizing differences in TIA mimics in younger and older patients to enhance diagnostic accuracy in elderly patients.Methods: In a dedicated neurological emergency room (nER) of a tertiary care University hospital, patients with transient neurological symptoms suspicious of TIA (70 years using descriptive, univariable, and multivariable statistics.Results: From November 2018 until August 2019, 386 consecutive patients were included. 271 (70%) had cardiovascular risk factors and all patients received cerebral imaging, mostly CT [376 (97%)]. There was no difference in the rate of diagnosed TIA between the age groups [85 (46%) vs. 58 (39%); p = 0.213].TIA mimics in the elderly were more often internal medicine diseases [35 (19%) vs. 7 (5%); p < 0.001] and epileptic seizures [48 (26%) vs. 24 (16%); p = 0.032] but less often migraine [2 (1%) vs. 20 (13%); p < 0.001]. The most frequent symptoms in all patients were aphasia and dysarthria [107 (28%) and 92 (24%)]. Sensory impairments were less frequent in elderly patients [23 (11%) vs. 54 (30%); p < 0.001]. Impaired consciousness and orientation were independent predictors for TIA mimics (p < 0.001) whereas facial palsy (p < 0.001) motor weakness (p < 0.001), dysarthria (p = 0.022) and sensory impairment (p < 0.001) were independent predictors of TIA.Conclusion: TIA mimics in elderly patients are more likely to be internal medicine diseases and epilepsy compared to younger patients. Excluding internal medicine diseases seems to be important in elderly patients. Facial palsy, motor weakness, dysarthria and sensory impairment are associated with TIA.

Despite successful recanalization of large-vessel occlusions in acute ischemic stroke, individual patients profit to a varying degree. Dynamic susceptibility-weighted perfusion and dynamic T1-weighted contrast-enhanced blood-brain barrier permeability imaging may help to determine secondary stroke injury and predict clinical outcome. We prospectively performed perfusion and permeability imaging in 38 patients within 24 h after successful mechanical thrombectomy of an occlusion of the middle cerebral artery M1 segment. Perfusion alterations were evaluated on cerebral blood flow maps, blood-brain barrier disruption (BBBD) visually and quantitatively on ktrans maps and hemorrhagic transformation on susceptibility-weighted images. Visual BBBD within the DWI lesion corresponded to a median ktrans elevation (IQR) of 0.77 (0.41–1.4) min−1 and was found in all 7 cases of hypoperfusion (100%), in 10 of 16 cases of hyperperfusion (63%), and in only three of 13 cases with unaffected perfusion (23%). BBBD was significantly associated with hemorrhagic transformation (p

Supplemental material, sj-pdf-1-neu-10.1177_19714009211015771 for Accuracy and reliability of PBV ASPECTS, CBV ASPECTS and NCCT ASPECTS in acute ischaemic stroke: a matched-pair analysis by Arne Potreck, Alina Falbesaner, Fatih Seker, Charlotte S Weyland, Sibu Mundiyanapurath, Sabine Heiland, Martin Bendszus and Johannes AR Pfaff in The Neuroradiology Journal

BACKGROUND: We analyzed the effects of the SARS-CoV-2 pandemic on neurologic emergencies, depending on the patients' triage score in a setting with relatively few COVID-19 cases and without lack of resources. METHODS: Consecutive patients of a tertiary care center with a dedicated neurologic emergency room (nER) were analyzed. The time period of the first lockdown in Germany (calendar weeks 12-17, 2020) was retrospectively compared to the corresponding period in 2019 regarding the number of patients presenting to the nER, the number of patients with specific triage scores (Heidelberg Neurological Triage Score), the number of patients with stroke, and the quality of stroke care. RESULTS: A total of 4330 patients were included. Fewer patients presented themselves in 2020 compared to 2019 (median [interquartile range] per week: 134 [118-143] vs. 187 [182-192]; p = 0.015). The median numbers of patients per week with triage 1 (emergent) and 4 (non-urgent) were comparable (51 [43-58] vs. 59 [54-62]; p = 0.132, and 10 [4-16] vs. 16 [7-18]; p = 0.310, respectively).The median number of patients per week declined in categories 2 and 3 in 2020 (41 [37-45] vs. 57 [52-61]; p = 0.004, and 28 [23-35] vs. 61 [52-63]; p = 0.002, respectively. No change was observed in the absolute number of strokes (138 in 2019 and 141 in 2020). Quality metrics of stroke revascularization therapies (symptom-to-door time, door-to-needle time or relative number of therapies) and stroke severity remained constant. CONCLUSION: During the lockdown period in 2020, the number of patients with emergent symptoms remained constant, while fewer patients with urgent symptoms presented to the nER. This may imply behavioral changes in care-seeking behavior.

Background An extended time window for intravenous thrombolysis (IVT) for acute stroke patients up to 9 hours from symptom onset has been established in recent trials, excluding patients who received mechanical thrombectomy (MT). We therefore investigated whether combined therapy with IVT and MT (IVT+MT) is safe in patients with ischemic stroke and large vessel occlusion (LVO) in an extended time window. Methods We retrospectively analyzed patients with anterior circulation ischemic stroke and LVO who were treated within 4.5 to 9 hours after symptom onset using MT with or without IVT. Primary endpoint was the occurrence of any intracranial hemorrhage (ICH). Multivariable logistic regression was used to adjust for potential confounders. Results In total, 168 patients were included in the study, 44 (26%) were treated with IVT+ MT. 133 (79%) patients had a M1-/distal carotid artery occlusion. Median ASPECT-Score was 8 (IQR 7-10) and complete reperfusion (mTICI 2b-3) was achieved in 132 (79%) patients. 18 (41%) of the patients in the IVT+MT group developed any ICH vs. 45 (36%) patients in the direct MT group (p=0.587). Symptomatic ICH occurred in 5 (11%) patients with IVT+MT vs. 8 (6%) patients receiving direct MT (p=0.295). In multivariable analysis, IVT+MT was not an independent predictor of ICH (adjusted for NIHSS, degree of reperfusion, symptom-onset-to-treatment time and therapy with tirofiban; OR 0.95 [95% CI 0.43-2.08], p=0.896). Conclusion Mechanical thrombectomy in stroke patients seems to be safe with combined intravenous thrombolysis within 4.5 to 9 hours after onset as it did not significantly increase the risk for intracranial hemorrhage.

Additional file 1: Table S1. Comparison of PaCO2 and PaO2 by delayed cerebral ischemia (DCI; n = 150).

Background While both hypercapnia and hypocapnia are harmful in patients with subarachnoid hemorrhage (SAH), it is unknown whether high-normal PaCO2 values are better than low-normal values. We hypothesized that high-normal PaCO2 values have more detrimental than beneficial effects on outcome. Methods Consecutive patients with aneurysmal subarachnoid hemorrhage (aSAH) requiring mechanical ventilation treated in a tertiary care university hospital were retrospectively analyzed regarding the influence of PaCO2 on favorable outcome, defined as modified Rankin scale score

Neurological syndromes are underrepresented in existing triage systems which are not validated for neurological patients; therefore, we developed and validated the new Heidelberg Neurological Triage System (HEINTS) in a prospective, single-center observational study. Patients were triaged according to the new triage system by nurses and physicians (stage 1) as well as trained nurses (stage 2). In stage 1, all patients presenting to the neurological emergency room (ER) were triaged by nurses and physicians. In stage 2, three specially trained nurses triaged patients according to HEINTS. The main outcomes comprised interrater agreement between nurses’ and physicians’ triage (stage 1), sensitivity and specificity to detect emergencies (stages 1 and 2), and improvement in triage quality as a result of training (stage 2), as well as correlation of HEINTS with hospital admissions and resource utilization. In stage 1 (n = 2423 patients), sensitivity and specificity to detect neurological emergencies were 84.2% (SD 0.8%) and 85.4% (SD 0.8%) for nurses, as well as 92.4% (SD 0.6%) and 84.1% (SD 0.9%) for physicians, respectively. The interrater-reliability between nurses and physicians in stage 1 was moderate [Cohen’s kappa 0.44, standard deviation (SD) 0.02]. In stage 2 (n = 506 patients), sensitivity of trained nurses increased to 94.3% (SD 1.0%), while specificity decreased to 74.8% (SD 1.9%). Correlation of HEINTS triage with hospital admission and resource utilization in both stages was highly significant. HEINTS predicted hospital admissions and resource utilization. Agreement between nurses and physicians was moderate. HEINTS, applied by physicians and by nurses after training, reliably detected neurological emergencies.

Introduction: Trimethylamine-N-oxide (TMAO ) is a biomarker of the gut microbiome and has been reported to be associated with cardiovascular diseases. However, there have been conflicting reports regarding its association with ischemic stroke. As TMAO values could be elevated before stroke or change after stroke we aimed at analyzing the early time course of TMAO values after acute ischemic stroke. Methods: In this prospective ongoing case-control study, we included patients with ischemic stroke within the first 24 hours after last-seen-well and control patients treated for other neurologic disorders with only few cardiovascular risk factors at a tertiary care university hospital. The TMAO-values on admission and after 48 hours were analyzed. Patients and controls were excluded if they were treated with antibiotics within the last 30 days and if they were treated with probiotics or chemotherapy. Results: 99 patients have been recruited so far (63 stroke patients and 36 controls). The median NIHSS score in stroke patients was 3 (interquartile range: 1-8). 89% of the stroke patients vs. 94% of the control group had a normal kidney function. Stroke patient had significantly higher median TMAO values compared to control patients: 5.4 (3.0-8.0) vs. 2.8 (1.6-5.0) μmol/l, p=0.002. Interestingly, there was a significant decrease in TMAO values in stroke patients from admission to 48 hours after the stroke (median decrease 0.7 (0.6-4.2) p=0.004), which was not found for the control group (median decrease 0.1 (-0.9-1.3), p=0.758). In consequence, there was no significant difference between the groups for the TMAO-values after 48 hours (3.4 (2.5-5.1) vs. 3.0 (1.6-4.5) μmol/l, p=0.081). Conclusion: This study emphasizes the importance of the TMAO time course after stroke. TMAO values decrease dramatically within the first days after stroke which makes it essential to standardize the time point of analysis to ensure comparability in future studies.

Purpose Chemical exchange sensitive spin-lock and related techniques allow to observe the uptake of administered D-glucose in vivo. The exchange-weighting increases with the magnetic field strength, but inhomogeneities in the radiofrequency (RF) field at ultrahigh field whole-body scanners lead to artifacts in conventional spin-lock experiments. Thus, our aim was the development of an adiabatically prepared T1ρ-based imaging sequence applicable to studies of glucose metabolism in tumor patients at ultrahigh field strengths. Methods An adiabatically prepared on-resonant spin-lock approach was realized at a 7 Tesla whole-body scanner and compared with conventional spin-lock. The insensitivity to RF field inhomogeneities as well as the chemical exchange sensitivity of the approach was investigated in simulations, model solutions and in the human brain. Results The suggested spin-lock approach was shown to be feasible for in vivo application at ultrahigh field whole-body scanners and showed substantially improved image quality compared with conventional spin-lock. The sensitivity of the presented method to glucose was verified in model solutions and a glucose contrast was observed in a glioblastoma patient after intravenous administration of glucose solution. Conclusion An adiabatically prepared spin-lock preparation was presented that enables a homogeneous and chemical exchange sensitive T1ρ-based imaging at ultra-high field whole-body scanners, e.g., for T1ρ-based dynamic glucose enhanced MRI. Magn Reson Med 78:215–225, 2017. © 2016 International Society for Magnetic Resonance in Medicine

Background and purpose Internal carotid artery (ICA) stenosis can lead to cerebral hypoperfusion and is a common cause of stroke. As susceptibility weighted imaging (SWI) has been used for penumbra imaging in acute ischemic stroke, we aimed at analyzing hypoperfusion using SWI in patients with ICA stenosis. Material and methods Clinical characteristics, asymmetric cortical vessel sign (more and/or larger, hypointense asymmetric cortical vessels) on SWI, Doppler sonography results and diffusion weighted imaging (DWI) lesion volume were retrospectively analyzed in patients with ICA stenosis. In a subgroup of patients, volume of prolonged time to peak and volume of prolonged time to peak of the residue curve (Tmax) were measured as reference standard. Outcome was assessed as modified Rankin score at discharge. Results 104 patients were included. Median age was 72 and median degree of stenosis 70% according to NASCET. 13% had a asymmetric cortical vessel sign. These patients had a higher degree of stenosis (80% vs. 70%, p = 0.004), were more often symptomatic (93% vs. 61%, p = 0.020) and had higher DWI volume (7.3 ml vs. 0.2 ml, p = 0.011). Specificity for the prediction of DWI lesions was 86%. Also, patients with asymmetric cortical vessel sign had lower rates of favorable outcome (mRS = 0–2; 57% vs. 82%, p = 0.033) and volumes of Tmax ≥ 4 s, ≥6 s, ≥8 s, ≥10 s and TTP ≥ 2 s, ≥4 s, ≥6 s were significantly higher. In multivariate analysis, asymmetric cortical vessel sign was an independent negative predictor of favorable outcome (mRS 0–2; OR 0.184; CI [0.039; 0.875] p = 0.033). Conclusion In patients with ICA stenosis, asymmetric cortical vessel sign is a sign of clinically relevant hypoperfusion.

Background and Purpose Safety and efficacy of endovascular thrombectomy (EVT) in patients with mild stroke syndromes is unclear, especially in distal vessel occlusions. Methods We analysed in our stroke database (HeiReKa) between 2002 and April 2019 safety and efficacy of EVT compared to intravenous thrombolysis (IVT) in patients with occlusions distal to the M1 segment of the middle cerebral artery and the top of the basilar artery who presented with a National Institute of Health Stroke Scale (NIHSS) below 6. Excellent (good) outcome was defined as modified rankin scale (mRS) 0-1 (0-2) or return to baseline mRS (good) after 3 months. Safety endpoints were mortality after 3 months and intracranial hemorrhage according to the Heidelberg Bleeding Classification (HBC). Results Of 4167 patients 94 met the inclusion criteria. Sixty-four patients were allocated to the IVT group and 30 to the EVT group of which 15 also received IVT; three patients (4.6%) in the IVT group received rescue EVT. Baseline characteristics did not differ but more M2 occlusions were found in the EVT group (93.3% vs. 64.1%, p = 0.02). Intracranial bleeding occurred more often in EVT patients (HBC class 2: 13.3% vs. 1.6%, p = 0.01). Excellent and good outcome were not significantly different (75% vs. 70%, p = 0.65 and 87.5% vs. 73.3%, p = 0.14). Mortality was significantly lower in IVT patients (1.6% vs. 13.3%, p = 0.04). Conclusion Rates of excellent and good outcome after IVT or EVT were almost similar, but safety parameters were increased after EVT. EVT may be considered in selected patients after careful risk/benefit analysis.

Purpose To evaluate the ability to detect intracerebral regions of increased glucose concentration at T1ρ-weighted dynamic glucose-enhanced (DGE) magnetic resonance (MR) imaging at 7.0 T. Materials and Methods This prospective study was approved by the institutional review board. Nine patients with newly diagnosed glioblastoma and four healthy volunteers were included in this study from October 2015 to July 2016. Adiabatically prepared chemical exchange-sensitive spin-lock imaging was performed with a 7.0-T whole-body unit with a temporal resolution of approximately 7 seconds, yielding the time-resolved DGE contrast. T1ρ-weighted DGE MR imaging was performed with injection of 100 mL of 20% d-glucose via the cubital vein. Glucose enhancement, given by the relative signal intensity change at T1ρ-weighted MR imaging (DGEρ), was quantitatively investigated in brain gray matter versus white matter of healthy volunteers and in tumor tissue versus normal-appearing white matter of patients with glioblastoma. The median signal intensities of the assessed brain regions were compared by using the Wilcoxon rank-sum test. Results In healthy volunteers, the median signal intensity in basal ganglia gray matter (DGEρ = 4.59%) was significantly increased compared with that in white matter tissue (DGEρ = 0.65%) (P = .028). In patients, the median signal intensity in the glucose-enhanced tumor region as displayed on T1ρ-weighted DGE images (DGEρ = 2.02%) was significantly higher than that in contralateral normal-appearing white matter (DGEρ = 0.08%) (P.0001). Conclusion T1ρ-weighted DGE MR imaging in healthy volunteers and patients with newly diagnosed, untreated glioblastoma enabled visualization of brain glucose physiology and pathophysiologically increased glucose uptake and may have the potential to provide information about glucose metabolism in tumor tissue.

Background Whether patients suffering from acute ischemic stroke and undergoing endovascular recanalization should be treated under general anesthesia (GA) or conscious sedation (CS) is a matter of debate. According to retrospective studies, GA appears to be associated with a worse outcome than CS. The underlying mechanisms are unknown, but hypotension and hypocapnia during GA have been suggested. There are no prospective data on this question. Methods We prospectively analyzed consecutive patients who were treated with endovascular recanalization from 11, 2013 to 03, 2014 regarding blood pressure, end-tidal carbon dioxide (etCO 2 ), cerebral oximetry (by near-infrared spectroscopy), ventilation parameters, response to commands, basic parameters (age, gender, percentage of posterior circulation stroke, National Institutes of Health Stroke Scale score [NIHSSS] on admission, NIHSSS at discharge, rate of successful recanalization [thrombolysis in cerebral infarction scale >2a], duration of intervention, symptom-to-recanalization time, and door-to-needle time), and medication used. Results Forty-four patients (29 under GA and 15 in CS) were included. Significant differences between the groups (GA versus CS) were found in the median dose of norepinephrine (.4 mg/hour versus .1 mg/hour, P = .003), mean systolic blood pressure (139.67 mm Hg versus 155.00 mm Hg, P = .003), mean duration of relative hypotension (systolic blood pressure P = .004), and mean etCO 2 values (37.29 mm Hg versus 27.33 mm Hg, P = .004). Conclusions In this small prospective study, patients under CS required less vasopressor medication and had a higher mean blood pressure than those under GA, but they also showed signs of hyperventilation. The impact of these physiological differences on outcome needs to be studied in randomized trials.

Background The optimal peri-interventional management of sedation and airway for endovascular stroke treatment (EST) appears to be a crucial factor for treatment success. According to retrospective studies, the widely favored general anesthesia with intubation seems to be associated with poor functional outcome compared to a slightly sedated non-intubated condition (conscious sedation). Method SIESTA is a monocentric, prospective, randomized parallel-group, open-label treatment trial with blinded endpoint evaluation (PROBE design). The study compares the non-intubated with the intubated state in patients receiving endovascular treatment of acute ischemic anterior circulation stroke. The primary endpoint is early neurological improvement as by National Institutes of Health Stroke Scale (NIHSS) after 24 h (difference between NIHSS on admission and NIHSS after 24 h). Secondary endpoints include: functional outcome after three-months as by modified Rankin Scale (mRS), mortality, parameters of ventilation and critical care, feasibility, and safety, i.e. complications related to endovascular stroke treatment. Conclusion The aims of this study are to prospectively clarify whether the non-intubated state of conscious sedation is feasible, safe, and superior with regard to early neurological improvement compared to the intubated state of general anesthesia in patients receiving acute endovascular stroke treatment.

Background and purposeEndovascular recanalization in ischemic stroke is often performed under general anesthesia. Some studies have shown a detrimental effect of general anesthesia. The reasons are unknown.MethodsThis was an observational study with retrospective and prospective phases. From 2008 to 2010, 60 patients treated by endovascular recanalization due to proximal vessel occlusion were analyzed with regard to ventilation parameters, blood gas values, blood pressure, and clinical parameters (pre-protocol phase). Subsequently, a protocol with target values for end-tidal CO2 (Petco2) and systolic blood pressure (SBP) was introduced and prospectively analyzed in 64 patients in 2012 (protocol phase).ResultsIn the pre-protocol phase, significant hypocapnia (2 values and 55% of SBP values (median) of the duration of intervention were within the predefined range. Severe hypocapnia and hypotension (SBP 2 values within 40–45 mm Hg, intracerebral hemorrhage, longer door to needle time, older age, unsuccessful recanalization, longer duration of endovascular treatment, and higher cumulative dose of norepinephrine were associated with an unfavorable outcome (modified Rankin Scale score >2). Intracerebral hemorrhage (OR 0.028, p=0.001), age (OR 0.9, p=0.013), and cumulative dose of norepinephrine (OR 0.142, p=0.003) were independent predictors of an unfavorable outcome.ConclusionsIn patients receiving endovascular stroke treatment under general anesthesia, the cumulative dose of norepinephrine was an independent predictor of an unfavorable outcome. Further studies are needed to evaluate the optimal management of blood pressure in these patients, and whether avoidance of catecholamines could partly explain the improved outcomes for patients treated under conscious sedation in retrospective studies.

Background and Purpose The recent thrombectomy trials have shown that perfusion imaging is helpful in proper patient selection in thromboembolic stroke. In this study, we analyzed the correlation of pretreatment T max volumes in MR and CT perfusion with clinical outcome after thrombectomy. Methods Forty‐one consecutive patients with middle cerebral artery occlusion (MCA) or carotid T occlusion treated with thrombectomy were included. T max volumes at delays of >4, 6, 8, and 10 s as well as infarct core and mismatch ratio were automatically estimated in preinterventional MRI or CT perfusion using RAPID software. These perfusion parameters were correlated with clinical outcome. Outcome was assessed using modified Rankin scale at 90 days. Results In patients with successful recanalization of MCA occlusion, T max > 8 and 10 s showed the best linear correlation with clinical outcome (r = 0.75; p = .0139 and r = 0.73; p = .0139), better than infarct core (r = 0.43; p = .2592). In terminal internal carotid artery occlusions, none of the perfusion parameters showed a significant correlation with clinical outcome. Conclusions T max at delays of >8 and 10 s is a good predictor for clinical outcome in MCA occlusions. In carotid T occlusion, however, T max volumes do not correlate with outcome.

Introduction: Intravenous thrombolysis is the only approved pharmacological treatment for acute ischemic stroke. Due to strict license regulations, off-label treatment is common. We aimed to analyze the safety and efficacy of off-label thrombolysis. Methods: Retrospective analysis of 56258 patients from the Safe Implementation of Treatments in Stroke (SITS) thrombolysis registry was performed regarding 11 off-label criteria according to the European license for alteplase. Symptomatic intracranial hemorrhage (SICH) according to SITS was defined as primary safety endpoint and SICH according to the European Cooperative Acute Stroke Study II (ECASS II) definition and the National Institute of Neurological Disorders and Stroke (NINDS) definition as secondary safety endpoints. Favorable outcome, defined as modified Rankin Scale score 3 months after stroke between 0 and 2 was the primary efficacy endpoint. Multivariable logistic regression analyses after replacing missing values using multiple imputations were performed for the efficacy and safety endpoints. Results: In total, 16740 (30%) patients received off-label thrombolysis. SICH according to the SITS definition occurred in 1037 (1.8%) patients. The only two off-label criteria constituting independent positive and negative predictors for SICH according to the SITS definition were elevated blood pressure (OR 1.39; p=0.012) and minor stroke (OR 0.51; p=0.002). Very severe stroke, history of stroke and diabetes, age and high glucose levels were additional independent predictors of SICH according to the ECASS II and NINDS definition. Favorable outcome was found in 24834 patients (54.5%). Independent predictors of favorable outcome comprised of minor stroke (positive predictor) and very severe stroke, history of stroke and diabetes, age and elevated blood pressure (all negative predictors). Inclusion of SICH according to the ECASS II definition in the multivariable analysis did not change the OR of these off-label criteria. Conclusions: Thrombolysis appears to be safe and efficient for most of the off-label criteria. Individual risk-benefit evaluation should be performed before off-label thrombolysis, especially in patients with combinations of these off-label criteria.

Purpose To correlate histopathologic findings from biopsy specimens with their corresponding location within enhancing areas, non-enhancing areas and necrotic areas on contrast enhanced T1-weighted MRI scans (cT1). Materials and Methods In 37 patients with newly diagnosed glioblastoma who underwent stereotactic biopsy, we obtained a correlation of 561 1mm3 biopsy specimens with their corresponding position on the intraoperative cT1 image at 1.5 Tesla. Biopsy points were categorized as enhancing (CE), non-enhancing (NE) or necrotic (NEC) on cT1 and tissue samples were categorized as “viable tumor cells”, “blood” or “necrotic tissue (with or without cellular component)”. Cell counting was done semi-automatically. Results NE had the highest content of tissue categorized as viable tumor cells (89% vs. 60% in CE and 30% NEC, respectively). Besides, the average cell density for NE (3764 ± 2893 cells/mm2) was comparable to CE (3506 ± 3116 cells/mm2), while NEC had a lower cell density with 2713 ± 3239 cells/mm2. If necrotic parts and bleeds were excluded, cell density in biopsies categorized as “viable tumor tissue” decreased from the center of the tumor (NEC, 5804 ± 3480 cells/mm2) to CE (4495 ± 3209 cells/mm2) and NE (4130 ± 2817 cells/mm2). Discussion The appearance of a glioblastoma on a cT1 image (circular enhancement, central necrosis, peritumoral edema) does not correspond to its diffuse histopathological composition. Cell density is elevated in both CE and NE parts. Hence, our study suggests that NE contains considerable amounts of infiltrative tumor with a high cellularity which might be considered in resection planning.

Background and purpose Patients with ischemic stroke and large vessel occlusion are assumed to benefit from endovascular therapy (ET) independent of the symptom onset-to-treatment time (OTT) if they present with a mismatch of diffusion- and perfusion-weighted imaging (DWI-PWI mismatch). We aimed at studying the influence of OTT on clinical outcome in these patients. Methods Retrospective database review in a tertiary care university hospital. All patients presented with proximal vessel occlusion of the anterior circulation and DWI-PWI mismatch. Primary outcome was the influence of OTT on modified Rankin scale (mRS) score three months after treatment, dichotomized in favourable (0–2) and unfavourable outcome (3–6). Secondary outcome was the effect of OTT on the shift of the mRS score. Patients treated within an early time window ( Results 139 patients were included. The rate of favourable outcome was significantly higher in patients who were treated in an early compared to those treated in a late time window (31 [49%] vs. 20 patients [27%], p = 0.005). Adjusted multivariate logistic regression revealed that late treatment was an independent negative predictor of favourable outcome (odds ratio 0.39, confidence interval [0.18–0.84]; p = 0.016). A shift towards higher mRS scores for late treatment was evident (p = 0.015). In sensitivity analysis, OTT remained an independent predictor when evaluated as continuous variable. These findings were confirmed in patients with a comparable DWI-PWI mismatch according to the definitions from large trials (DEFUSE 2, DEFUSE 3, SWIFT-PRIME, EXTEND-IA). Conclusion Outcome of patients with comparable DWI-PWI mismatch is time-dependent.

Background Gamma-aminobutyric-acid B (GABA-B)-receptor encephalitis represents a novel entity among autoimmune CNS disorders. Most cases are characterised by limbic encephalitis. Case report A 63-year-old patient presented with acute vertigo, nausea and vomiting, facial palsy and dysarthria. He developed dysphagia, gait ataxia and, finally, respiratory failure. Antibodies to GABA-B receptors were positive and declined under treatment with intravenous methylprednisolone and plasma exchange, followed by clinical improvement and stabilisation. Broad tumour screening revealed oesophageal carcinoma. Conclusion The spectrum of neurological manifestations and tumours associated with the paraneoplastic variant of anti-GABA-B-receptor encephalitis may be broader than previously reported.

Background: Prognostic signs for the identification of patients with acute spontaneous intracerebral hemorrhage (SICH) prone to hematoma expansion are limited. Contrast extravasation (spot signs, SpS) on computed tomographic angiography (CTA) may be a promising method to predict hematoma expansion in acute SICH. However, prospective data on the predictive value of the SpS on hematoma expansion and clinical outcome are still limited. We aimed to investigate associations between the presence of SpS, hematoma expansion, and clinical outcome in acute SICH. Methods: A prospective observational study was performed between 08/2008 and 08/2011. Patients with SICH presenting within 6 h of symptom onset were included. Patients with secondary hematomas, purely intraventricular hematomas, incomplete CT evaluation, hematoma evacuation prior to follow-up brain imaging, and incomplete follow-up data and those who refused to give consent for data analysis were excluded. CT and CTA brain imaging were carried out in all patients at baseline. After 24 h, follow-up brain imaging was performed. Hematoma location, hematoma volume, and substantial hematoma expansion were documented. CTA images were evaluated by two investigators for the presence of SpS. In all positive SpS cases, images were additionally reviewed by a third rater to achieve consensus for interpretating contrast extravasation. Clinical outcome was measured by the modified Rankin Scale (mRS) at discharge and at 3 months. Results: In total, 101 patients [median age 73 years (interquartile range 60-79); male 61.4%] were included in the analysis. Median time from onset to CTA was 128 min (interquartile range 90-209 min); median initial National Institute of Health Stroke Scale score was 16 (8-21). SpS were detected in 27 patients (26.7%). Cohen's kappa for the presence of SpS was 0.606, indicating moderate agreement. SpS patients had significantly higher initial hematoma volumes than patients without SpS (36.0 vs. 14.39 ml, p = 0.005). Hematoma expansion was significantly more frequent in SpS patients (59.3 vs. 21.6%, p < 0.001) and associated with the presence of SpS in the univariate analysis (OR 5.273; 95% CI 2.047-13.584, p = 0.001) and in multivariable analysis adjusted for the initial hematoma volume (OR 4.678, 95% CI 1.781-12.288, p = 0.002). Sensitivity of SpS to predict hematoma expansion was 0.5, specificity was 0.84. The positive likelihood ratio for SpS to predict hematoma expansion was 3.136 (95% CI 1.649-5.967), the negative likelihood ratio was 0.595 (95% CI 0.414-0.854). No difference in 3-month clinical outcome was observed between patients with and without SpS (median mRS score 4 and 4, p = 0.457). Conclusions: The clinical value of SpS needs to be further explored. Future studies should particularly focus on structured training procedures to identify SpS and measure the time needed to precisely assess the presence of SpS and on the prevalence of SpS in consecutive intracerebral hemorrhage populations.

Importance Optimal management of sedation and airway during thrombectomy for acute ischemic stroke is controversial due to lack of evidence from randomized trials. Objective To assess whether conscious sedation is superior to general anesthesia for early neurological improvement among patients receiving stroke thrombectomy. Design, Setting, and Participants SIESTA (Sedation vs Intubation for Endovascular Stroke Treatment), a single-center, randomized, parallel-group, open-label treatment trial with blinded outcome evaluation conducted at Heidelberg University Hospital in Germany (April 2014-February 2016) included 150 patients with acute ischemic stroke in the anterior circulation, higher National Institutes of Health Stroke Scale (NIHSS) score (>10), and isolated/combined occlusion at any level of the internal carotid or middle cerebral artery. Intervention Patients were randomly assigned to an intubated general anesthesia group (n = 73) or a nonintubated conscious sedation group (n = 77) during stroke thrombectomy. Main Outcomes and Measures Primary outcome was early neurological improvement on the NIHSS after 24 hours (0-42 [none to most severe neurological deficits; a 4-point difference considered clinically relevant]). Secondary outcomes were functional outcome by modified Rankin Scale (mRS) after 3 months (0-6 [symptom free to dead]), mortality, and peri-interventional parameters of feasibility and safety. Results Among 150 patients (60 women [40%]; mean age, 71.5 years; median NIHSS score, 17), primary outcome was not significantly different between the general anesthesia group (mean NIHSS score, 16.8 at admission vs 13.6 after 24 hours; difference, −3.2 points [95% CI, −5.6 to −0.8]) vs the conscious sedation group (mean NIHSS score, 17.2 at admission vs 13.6 after 24 hour; difference, −3.6 points [95% CI, −5.5 to −1.7]); mean difference between groups, −0.4 (95% CI, −3.4 to 2.7; P = .82). Of 47 prespecified secondary outcomes analyzed, 41 showed no significant differences. In the general anesthesia vs the conscious sedation group, substantial patient movement was less frequent (0% vs 9.1%; difference, 9.1%; P = .008), but postinterventional complications were more frequent for hypothermia (32.9% vs 9.1%; P P P = .03). More patients were functionally independent (unadjusted mRS score, 0 to 2 after 3 months [37.0% in the general anesthesia group vs 18.2% in the conscious sedation group P = .01]). There were no differences in mortality at 3 months (24.7% in both groups). Conclusions and Relevance Among patients with acute ischemic stroke in the anterior circulation undergoing thrombectomy, conscious sedation vs general anesthesia did not result in greater improvement in neurological status at 24 hours. The study findings do not support an advantage for the use of conscious sedation. Trial Registration clinicaltrials.gov Identifier:NCT02126085

IntroductionEndovascular therapy in acute ischemic stroke is safe and efficient. However, patients receiving oral anticoagulation were excluded in the larger trials.ObjectiveTo analyze the safety of endovascular therapy in patients with acute ischemic stroke and elevated international normalized ratio (INR) values.MethodsRetrospective database review of a tertiary care university hospital for patients with anterior circulation stroke treated with endovascular therapy. Patients with anticoagulation other than vitamin K antagonists were excluded. The primary safety endpoint was defined as symptomatic intracranial hemorrhage (sICH; ECASS II definition). The efficacy endpoint was the modified Rankin scale (mRS) score after 3 months, dichotomized into favorable outcome (mRS 0–2) and unfavorable outcome (mRS 3–6).Results435 patients were included. 90% were treated with stent retriever. 27 (6.2%) patients with an INR of 1.2–1.7 and 21 (4.8%) with an INR >1.7. 33 (7.6%) had sICH and 149 patients (34.3%) had a favorable outcome. Patients with an elevated INR did not have an increased risk for sICH or unfavorable outcome in multivariable analysis. The additional use of IV thrombolysis in patients with an INR of 1.2–1.7 did not increase the risk of sICH or unfavorable outcome. These results were replicated in a sensitivity analysis introducing an error of the INR of ±5%. They were also confirmed using other sICH definitions (Safe Implementation of Thrombolysis in Stroke (SITS), National Institute of neurological Disorders and Stroke (NINDS), Heidelberg bleeding classification).ConclusionsEndovascular therapy in patients with an elevated INR is safe and efficient. Patients with an INR of 1.2–1.7 may be treated with combined IV thrombolysis and endovascular therapy.

Chemical exchange sensitive spin-lock and related techniques allow to observe the uptake of administered D-glucose in vivo. The exchange-weighting increases with the magnetic field strength, but inhomogeneities in the radiofrequency (RF) field at ultrahigh field whole-body scanners lead to artifacts in conventional spin-lock experiments. Thus, our aim was the development of an adiabatically prepared TAn adiabatically prepared on-resonant spin-lock approach was realized at a 7 Tesla whole-body scanner and compared with conventional spin-lock. The insensitivity to RF field inhomogeneities as well as the chemical exchange sensitivity of the approach was investigated in simulations, model solutions and in the human brain.The suggested spin-lock approach was shown to be feasible for in vivo application at ultrahigh field whole-body scanners and showed substantially improved image quality compared with conventional spin-lock. The sensitivity of the presented method to glucose was verified in model solutions and a glucose contrast was observed in a glioblastoma patient after intravenous administration of glucose solution.An adiabatically prepared spin-lock preparation was presented that enables a homogeneous and chemical exchange sensitive T

Parameters of the ROC-Curve-Analysis. (DOCX 16 kb)

Background and purpose Intravenous thrombolysis (IVT) is the only approved pharmacological treatment for acute ischemic stroke. Off-label IVT for ischemic stroke is common. We aimed to analyse its safety in a large database. Methods This was a retrospective analysis of the safe implementation of treatments in stroke (SITS) thrombolysis registry with regard to 11 off-label criteria according to the European licence for alteplase. Symptomatic intracranial haemorrhage (SICH) according to SITS was defined as primary safety endpoint and SICH according to the European Cooperative Acute Stroke Study (ECASS II) definition and the National Institute of Neurological Disorders and Stroke definition as secondary safety endpoints. Multivariable logistic regression analyses after replacing missing values using multiple imputations were performed. Results Patients from 793 centres in 44 countries were included, mainly (95%) in Europe. A total of 56 258 patients who were treated with intravenous alteplase were included. Median age was 71 (IQR 61-78) years and median National Institutes of Health Stroke Scale score was 12 (IQR 7-17). A total of 16 740 (30%) patients received off-label IVT and 1037 (1.8%) patients suffered from SICH according to the SITS definition (SICH SITS). Median percentage of missing values per variable was 0.4%. The only two off-label criteria constituting independent positive and negative predictors for SICH SITS were high blood pressure (odds ratio, 1.39; 95% confidence interval, 1.08-1.80; P = 0.012) and minor stroke (odds ratio, 0.51; 95% confidence interval, 0.33-0.78; P = 0.002). Very severe stroke, previous stroke and diabetes, age and high glucose levels were additional independent predictors of SICH according to the ECASS II and National Institute of Neurological Disorders and Stroke definitions. Conclusions Thrombolysis appears to be safe with regard to SICH for most of the off-label criteria, especially for minor stroke, but is risky in patients with high blood pressure. Individual risk-benefit evaluation should be performed.