Search

Background: Mechanical thrombectomy is a cornerstone treatment for acute ischemic stroke (AIS) with large vessel occlusion (LVO), yet the optimal technique remains debated. The SOFIA/SOFIA PLUS catheter has emerged as a promising tool for direct aspiration thrombectomy., Purpose: This prospective multi-center study, adhering Good-Clinical-Practice guidelines, aimed to evaluate the safety and efficacy of the SOFIA/SOFIA PLUS catheter for direct aspiration as a first-line treatment technique in patients with acute anterior circulation LVO., Materials and Methods: Between 10/2017 and 12/2021, 246 consecutive patients presenting with AIS due to anterior circulation LVO were enrolled from 14 European centers. Primary treatment with SOFIA catheters was performed within 6 h of symptom onset. Clinical and radiological data were collected, and statistical analyses were conducted., Results: The mean age of the included patients was 71.6 ± 13.9 years, with 44.7% being male. Primary aspiration achieved complete recanalization in 72.8% of patients, with functional independence observed in 63.8% after 90 days. Secondary outcomes included a median NIHSS of 4 at 24 h post-procedure, median ASPECTS of 7 on follow-up imaging, and a mortality rate of 24.4% at 90 days. No device malfunctions were observed, and the rate of symptomatic intracranial hemorrhage was 4.4%., Conclusion: Primary aspiration with the SOFIA/SOFIA PLUS catheter demonstrates favorable safety and efficacy profiles in the treatment of anterior circulation LVO. These findings support the utilization of this technique as a first-line approach in mechanical thrombectomy for AIS, contributing to the growing body of evidence endorsing the effectiveness of direct aspiration thrombectomy in stroke management., Competing Interests: GT has received compensation by the University Heidelberg for activities as member of the CEC within the study, and fees as consultant or lecturer from Acandis, Alexion, Amarin, Astra Zeneca, Bayer, Boehringer Ingelheim, BristolMyersSquibb, Daiichi Sankyo, Portoly, Stryker outside this study. GM reports consulting fees from Microvention Europe, Stryker Neurovascular, Balt SAS, Sim and Cure and paid lectures from Medtronic, Phenox, Cerenovus, Bracco. All of these were outside this study. AP is the principal investigator of the SEALANT study sponsored by Microvention. MM received research grants from Acandis, Balt, Medtronic, Microvention, Phenox, Stryker* (*industry payments are made to the research fund of the institution), receives payment or honoraria for lectures from Balt, Medtronic, Stryker* (*industry payments are made to the research fund of the institution). SESAME was an investigator-initiated study (IIT). A grant for conducting the study was provided by Microvention. However, Microvention did not exert any influence on the study’ design. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Neuberger, Marnat, Barreau, Pitrone, Caragliano, Killer-Oberpfalzer, Pfaff, Maurer, Berlis, Bokkers, Uyttenboogaart, Sourour, Clarençon, Wodarg, Cognard, Bohner, Trenkler, Spelle, Weber, Nouri, Bonekamp, Thomalla, Fiehler, Bendszus and Möhlenbruch.)

Introduction: The deterioration of white matter pathways is one of the hallmarks of the ageing brain. In theory, this decrease in structural integrity leads to disconnection between regions of brain networks and thus to altered functional connectivity and a decrease in cognitive abilities. However, in many studies, associations between structural and functional connectivity are rather weak or not observed at all. System segregation, defined as the extent of partitioning between different resting state networks has increasingly gained attention in recent years as a new metric for functional changes in the aging brain. Yet there is a shortage of previous reports describing the association of structural integrity and functional segregation., Methods: Therefore, we used a large a large sample of 2,657 participants from the Hamburg City Health Study, a prospective population-based study including participants aged 46-78 years from the metropolitan region Hamburg, Germany. We reconstructed structural and functional connectomes to analyze whether there is an association between age-related differences in structural connectivity and functional segregation, and whether this association is stronger than between structural connectivity and functional connectivity. In a second step, we investigated the relationship between functional segregation and executive cognitive function and tested whether this association is stronger than that between functional connectivity and executive cognitive function., Results: We found a significant age-independent association between decreasing structural connectivity and decreasing functional segregation across the brain. In addition, decreasing functional segregation showed an association with decreasing executive cognitive function. On the contrary, no such association was observed between functional connectivity and structural connectivity or executive function., Discussion: These results indicate that the segregation metric is a more sensitive biomarker of cognitive ageing than functional connectivity at the global level and offers a unique and more complementary network-based explanation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Schulz, Petersen, Cheng and Thomalla.)

Introduction: Although people spend most of the day in their home environment, the focus of research in environmental psychology to date has been on factors outside the home. However, it stands to reason that indoor quality likewise has an impact on psychological well-being. Therefore, the present study addresses the question of whether the subjective evaluation of home environmental parameters are related to self-reported anxiety and whether they can additionally explain variance beyond the usual sociodemographic and general lifestyle variables., Methods: Data from the Hamburg City Health Study (first 10,000 participants) was analyzed. A subsample of N = 8,886 with available GAD-7 anxiety data was selected, and hierarchical regression models were computed, with demographic data entered first, followed by variables concerning lifestyle/habits and finally variables of the subjective evaluation of home environment., Results: Using the integrated model, we were able to explain about 13% of the variance in self-reported anxiety scores. This included both the demographic, lifestyle, and subjective evaluation of home environment variables. Protection from disturbing night lights, a greater sense of security, less disturbing noises, brighter accommodations, and a satisfactory window view explained almost 6% of the variance and was significantly associated with lower anxiety scores., Conclusion: The home as a place of refuge plays an increasingly important role as home office hours rise. It is therefore crucial to identify domestic factors contributing to people's mental well-being. The subjective evaluation of one's home environment has proven influential over and above modifiable lifestyle variables., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Weber, Mascherek, Augustin, Cheng, Thomalla, Hoven, Harth, Augustin, Gallinat and Kühn.)

Introduction: This study assesses the association of comorbidity burden and polypharmacy with self-reported quality of life after stroke., Patients and Methods: We performed a post-hoc analysis of a prospective, single-center, observational study of outcome evaluation by patient-reported outcome measures in stroke clinical practice. Consecutive patients with acute ischemic stroke (AIS) were enrolled and self-reported health-related quality of life (HrQoL) was assessed 90 days after acute stroke using the Patient-reported Outcomes Measurement Information System 10-Question Short-Form (PROMIS-10). Comorbidities at baseline were assessed by the Charlson Comorbidity Index (CCI). Polypharmacy was defined as medication intake of ≥5 at baseline. We used linear regression analysis to study the association of CCI, polypharmacy and other clinical covariates with HrQoL after stroke., Results: Of 781 patients (median age 76 years, 48.4% female) enrolled, 30.2% had a CCI Score ≥2, and 31.5% presented with polypharmacy. At follow up, 71 (9.1%) had died. In 409 (52.4%) reached for outcome evaluation, Global Physical Health T-Score was 43.8 ± 10 and Global Mental Health T-Score was 43.5 ± 8.76, indicating lower HrQoL than the average population. A CCI Score ≥2, higher NIHSS Score, female sex, dependency on others for dressing, toileting and mobility before index stroke, atrial fibrillation and hypertension were independent predictors of worse physical and mental health outcomes, while polypharmacy was not., Conclusion: In patients with AIS, high comorbidity burden and polypharmacy are frequent. Comorbidity burden at admission is independently associated with worse self-reported physical and mental health three months after stroke., Competing Interests: Author CG reports personal fees from Amgen, Bayer Vital, Bristol-Myers Squibb, Boehringer Ingelheim, Sanofi Aventis, Abbott, and Prediction Biosciences outside the submitted work. Author GT reports receiving consulting fees from Acandis, grant support, and lecture fees from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb/Pfizer and Daiichi Sankyo, and consulting fees and lecture fees from Stryker outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Heinze, Lebherz, Rimmele, Frese, Jensen, Barow, Lettow, Kriston, Gerloff, Härter and Thomalla.)

Background: Successful reperfusion (mTICI 2c/3) and low number of passes are key determinants for good clinical outcome in acute large vessel occlusion. While final mTICI 2c/3 reperfusion is superior to partial reperfusion (mTICI 2b) it remains unclear if this is also true for the subgroup of patients with early mTICI 2b (achieved in ≤2 retrieval attempts) reperfusion who are secondarily improved to mTICI 2c/3. This study was designed to examine if early mTICI2b should be continued or stopped during mechanical thrombectomy (MT)., Methods: Nine hundred and thirteen ischemic stroke patients who received MT were retrospectively analyzed. Angiography runs following each recanalization attempt were scored for mTICI. The patients with early mTICI 2b reperfusions were dichotomized in "TICI2b-stopped" (MT withdrawal after mTICI 2b was achieved with first or second retrieval) and "TICI2b-continued" (MT was continued after mTICI 2b was achieved with first or second retrieval). Functional outcome was obtained after 90 days using the modified Rankin scale (mRS90)., Results: Of 362 Patients with a M1-occlusion, 100 patients fulfilled the inclusion criteria with an early mTICI 2b. 78/100 patients were included in the "TICI2b-stopped" group and 22/100 patients were in the "TICI2b-continued" group. Of these 22 patients, none had a final mTICI score lower than 2b and 11 patients had a final mTICI score of 2c/3. Regarding good functional outcome at mRS90, "TICI2b-continued" showed by trend a slight advantage of 40.1 vs. 35.6% in "TICI2b-stopped" but in multivariate logistic regression analysis adjusted for confounders, no significant difference was found between the two groups (OR 0.75, 95% CI 0.19-2.87, p = 0.67). Symptomatic intracranial hemorrhage was significantly higher in "TICI2b-continued" compared to "TICI2b-stopped" (31.8 vs. 10.3%, p = 0.031)., Conclusion: Successfully improving an early mTICI 2b to mTICI 2c/3 reperfusion is possible in a substantial number of patients and might improve functional outcome. However, an increase in symptomatic intracranial hemorrhage (SICH) due to further retrieval attempts may diminish the potential functional benefit to continue early mTICI 2b. To support this finding, further investigation with more power is needed to account for the low number of events regarding SICH., Competing Interests: Author GT reports personal fees from Acandis, grants and personal fees from Bayer, personal fees from Bristol Myers Squibb/Pfizer, personal fees from Boehringer Ingel-heim, personal fees from Daiichi Sankyo, personal fees from Portola, and personal fees from Stryker outside the submitted work. Author JF reports grants and personal fees from Acandis, grants and personal fees from Cerenovus, grants and personal fees from Medtronic, grants and personal fees from Microvention, personal fees from Penumbra, and personal fees from Phenox outside the submitted work, and chief executive officer of Eppdata. Author FF reports personal fees from Eppdata GmbH outside the sub-mitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Steffen, Van Horn, McDonough, Deb-Chatterji, Alegiani, Thomalla, Fiehler and Flottmann.)

Introduction: Higher white blood cell (WBC) count is associated with poor functional outcome in acute ischemic stroke (AIS). However, little is known about whether the association is modified by treatment with intravenous alteplase., Methods: WAKE-UP was a randomized controlled trial of the efficacy and safety of magnetic resonance imaging [MRI]-based thrombolysis in unknown onset stroke. WBC count was measured on admission and again at 22-36 h after randomization to treatment (follow-up). Favorable outcome was defined by a score of 0 or 1 on the modified Rankin scale (mRS) 90 days after stroke. Further outcome were stroke volume and any hemorrhagic transformation (HT) that were assessed on follow-up CT or MRI. Multiple logistic regression analysis was used to assess the association between outcome and WBC count and treatment group., Results: Of 503 randomized patients, WBC count and baseline parameters were available in 437 patients (μ = 64.7 years, 35.2% women) on admission and 355 patients (μ = 65.1 years, 34.1% women) on follow-up. Median WBC count on admission was 7.6 × 10 9 /L (interquartile range, IQR, 6.1-9.4 × 10 9 /L) and 8.2 × 10 9 /L (IQR, 6.7-9.7 × 10 9 /L) on follow-up. Higher WBC count both on admission and follow-up was associated with lower odds of favorable outcome, adjusted for age, National Institutes of Health (NIH) Stroke Scale Score, temperature, and treatment (alteplase vs. placebo, adjusted odds ratio, aOR 0.85, 95% confidence interval [CI] 0.78-0.94 and aOR 0.88, 95% CI 0.79-0.97). No interaction between WBC count and treatment group was observed ( p = 0.11). Furthermore, WBC count on admission and follow-up was significantly associated with HT (aOR 1.14, 95% CI 1.05-1.24 and aOR 1.13, 95% CI 1.00-1.26). Finally, WBC count on follow-up was associated with larger stroke volume (aOR 2.57, 95% CI 1.08-6.07)., Conclusion: Higher WBC count is associated with unfavorable outcome, an increased risk of HT, and larger stroke volume, independent of treatment with alteplase. Whether immunomodulatory manipulation of WBC count improves stroke outcome needs to be tested., Trial Registration: ClinicalTrials.gov Identifier: NCT01525290., Competing Interests: EB, BC, AK, FB, NN, MEb, MEn, JF, VT, RL, KM, SP, CS, CG, and GT report grants from European Union 7th Framework Program during the conduct of the study. MEn reports grants from Bayer and fees paid to the Charité from AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Daiichi Sankyo, Amgen, GSK, Sanofi, Covidien, Novartis, Pfizer and funding from DFG under Germany's Excellence Strategy – EXC-2049 – 390688087, BMBF, DZNE, DZHK, EU, Corona Foundation, and Fondation Leducq, all outside the submitted work. JF reports personal fees from Abbvie, AC Immune, Artemida, Bioclinica/Clairo, Biogen, BMS, Brainomic, Daiichi-Sankyo, Eisai, F.Hoffmann-La Roche AG, Eli Lilly, Guerbet, Ionis Pharmaceuticals, IQVIA, Janssen, Julius Clinical, Jung Diagnostics, Lysogene, Premier Research and Tau Rx, all outside the submitted work. CS reports grants from Novo Nordisk Foundation and Health Research Foundation of Central Denmark Region outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Barow, Quandt, Cheng, Gelderblom, Jensen, Königsberg, Boutitie, Nighoghossian, Ebinger, Endres, Fiebach, Thijs, Lemmens, Muir, Pedraza, Simonsen, Gerloff and Thomalla.)

Aging is accompanied by structural brain changes that are thought to underlie cognitive decline and dementia. Yet little is known regarding the association between increasing age, structural brain damage, and alterations of functional brain connectivity. The aim of this study was to evaluate whether cortical thickness and white matter damage as markers of age-related structural brain changes are associated with alterations in functional connectivity in non-demented healthy middle-aged to older adults. Therefore, we reconstructed functional connectomes from resting-state functional magnetic resonance imaging (MRI) (rsfMRI) data of 976 subjects from the Hamburg City Health Study, a prospective population-based study including participants aged 45-74 years from the metropolitan region Hamburg, Germany. We performed multiple linear regressions to examine the association of age, cortical thickness, and white matter damage quantified by the peak width of skeletonized mean diffusivity (PSMD) from diffusion tensor imaging on whole-brain network connectivity and four predefined resting state networks (default mode, dorsal, salience, and control network). In a second step, we extracted subnetworks with age-related decreased functional connectivity from these networks and conducted a mediation analysis to test whether the effect of age on these networks is mediated by decreased cortical thickness or PSMD. We observed an independent association of higher age with decreased functional connectivity, while there was no significant association of functional connectivity with cortical thickness or PSMD. Mediation analysis identified cortical thickness as a partial mediator between age and default subnetwork connectivity and functional connectivity within the default subnetwork as a partial mediator between age and executive cognitive function. These results indicate that, on a global scale, functional connectivity is not determined by structural damage in healthy middle-aged to older adults. There is a weak association of higher age with decreased functional connectivity which, for specific subnetworks, appears to be mediated by cortical thickness., Competing Interests: The authors declare that this study received funding from Amgen, Astra Zeneca, Bayer, Badischen Anilin & Sodafabrik (BASF), Novartis, Pfizer, Schiller, Siemens, and Unilever. The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication., (Copyright © 2022 Schulz, Mayer, Schlemm, Frey, Malherbe, Petersen, Gallinat, Kühn, Fiehler, Hanning, Twerenbold, Gerloff, Cheng and Thomalla.)

Maintaining optimal cognitive functioning throughout the lifespan is a public health priority. Evaluation of cognitive outcomes following interventions to promote and preserve brain structure and function in older adults, and associated neural mechanisms, are therefore of critical importance. In this randomized controlled trial, we examined the behavioral and neural outcomes following mindfulness training ( n = 72), compared to a cognitive fitness program ( n = 74) in healthy, cognitively normal, older adults (65-80 years old). To assess cognitive functioning, we used the Preclinical Alzheimer Cognitive Composite (PACC), which combines measures of episodic memory, executive function, and global cognition. We hypothesized that mindfulness training would enhance cognition, increase intrinsic functional connectivity measured with magnetic resonance imaging (MRI) between the hippocampus and posteromedial cortex, as well as promote increased gray matter volume within those regions. Following the 8-week intervention, the mindfulness training group showed improved performance on the PACC, while the control group did not. Furthermore, following mindfulness training, greater improvement on the PACC was associated with a larger increase in intrinsic connectivity within the default mode network, particularly between the right hippocampus and posteromedial cortex and between the left hippocampus and lateral parietal cortex. The cognitive fitness training group did not show such effects. These findings demonstrate that mindfulness training improves cognitive performance in cognitively intact older individuals and strengthens connectivity within the default mode network, which is particularly vulnerable to aging affects. Clinical Trial Registration: [https://clinicaltrials.gov/ct2/show/NCT02628548], identifier [NCT02628548]., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sevinc, Rusche, Wong, Datta, Kaufman, Gutz, Schneider, Todorova, Gaser, Thomalla, Rentz, Dickerson and Lazar.)

Background and Aims: Fluid-attenuated inversion recovery (FLAIR) hyperintense vessels (FHVs) on MRI are a radiological marker of vessel occlusion and indirect sign of collateral circulation. However, the clinical relevance is uncertain. We explored whether the extent of FHVs is associated with outcome and how FHVs modify treatment effect of thrombolysis in a subgroup of patients with confirmed unilateral vessel occlusion from the randomized controlled WAKE-UP trial. Methods: One hundred sixty-five patients were analyzed. Two blinded raters independently assessed the presence and extent of FHVs (defined as the number of slices with visible FHV multiplied by FLAIR slice thickness). Patients were then separated into two groups to distinguish between few and extensive FHVs (dichotomization at the median <30 or ≥30). Results: Here, 85% of all patients ( n = 140) and 95% of middle cerebral artery (MCA) occlusion patients ( n = 127) showed FHVs at baseline. Between MCA occlusion patients with few and extensive FHVs, no differences were identified in relative lesion growth ( p = 0.971) and short-term [follow-up National Institutes of Health Stroke Scale (NIHSS) score; p = 0.342] or long-term functional recovery [modified Rankin Scale (mRS) <2 at 90 days poststroke; p = 0.607]. In linear regression analysis, baseline extent of FHV (defined as a continuous variable) was highly associated with volume of hypoperfused tissue (β = 2.161; 95% CI 0.96-3.36; p = 0.001). In multivariable regression analysis adjusted for treatment group, stroke severity, lesion volume, occlusion site, and recanalization, FHV did not modify functional recovery. However, in patients with few FHVs, the odds for good functional outcome (mRS) were increased in recombinant tissue plasminogen activator (rtPA) patients compared to those who received placebo [odds ratio (OR) = 5.3; 95% CI 1.2-24.0], whereas no apparent benefit was observed in patients with extensive FHVs (OR = 1.1; 95% CI 0.3-3.8), p -value for interaction was 0.11. Conclusion: While the extent of FHVs on baseline did not alter the evolution of stroke in terms of lesion progression or functional recovery, it may modify treatment effect and should therefore be considered relevant additional information in those patients who are eligible for intravenous thrombolysis. Clinical Trial Registration: Main trial (WAKE-UP): ClinicalTrials.gov, NCT01525290; and EudraCT, 2011-005906-32. Registered February 2, 2012., Competing Interests: JBF reports consulting and advisory board fees from BioClinica, Cerevast, Abbvie, AC Immune, Artemida, Brainomix, Biogen, BMS, Daiichi-Sankyo, Guerbet, Ionis Pharmaceuticals, Julius Clinical, Eli Lilly, Tau Rx, and EISAI outside the submitted work. MEn reports grants from Bayer and fees paid to the Charité from Bayer, Boehringer Ingelheim, BMS, Daiichi Sankyo, Amgen, GSK, Sanofi, Covidien, Novartis, and Pfizer, all outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Grosch, Kufner, Boutitie, Cheng, Ebinger, Endres, Fiebach, Fiehler, Königsberg, Lemmens, Muir, Nighoghossian, Pedraza, Siemonsen, Thijs, Wouters, Gerloff, Thomalla and Galinovic.)

Background: Hemorrhagic transformation (HT) is an important complication of intravenous thrombolysis with alteplase. HT can show a wide range from petechiae to parenchymal hematoma with mass effect with varying clinical impact. We studied clinical and imaging characteristics of patients with HT and evaluated whether different types of HT are associated with functional outcome. Methods: We performed a post-hoc analysis of WAKE-UP, a multicenter, randomized, placebo-controlled trial of MRI-guided intravenous alteplase in unknown onset stroke. HT was assessed on follow-up MRI or CT and diagnosed as hemorrhagic infarction type 1 and type 2 (HI1 and HI2, combined as HI), and parenchymal hemorrhage type 1 and type 2 (PH1 and PH2, combined as PH). Severity of stroke symptoms was assessed using the National Institutes of Health Stroke Scale (NIHSS) at baseline. Stroke lesion volume was measured on baseline diffusion weighted imaging (DWI). Primary endpoint was a favorable outcome defined as a modified Rankin Scale score 0-1 at 90 days. Results: Of 483 patients included in the analysis, 95 (19.7%) showed HI and 21 (4.4%) had PH. Multiple logistic regression analysis identified treatment with alteplase (OR, 2.08 [95% CI, 1.28-3.40]), baseline NIHSS score (OR, 1.11 [95% CI, 1.05-1.17]), DWI lesion volume (OR, 1.03 [95% CI, 1.01-1.05]), baseline glucose levels (OR, 1.01 [95% CI, 1.00-1.01]) and atrial fibrillation (OR, 3.02 [95% CI, 1.57-5.80]) as predictors of any HT. The same parameters predicted HI. Predictors of PH were baseline NIHSS score (OR, 1.11 [95% CI, 1.01-1.22]) and as a trend treatment with alteplase (OR, 2.40 [95% CI, 0.93-6.96]). PH was associated with lower odds of favorable outcome (OR 0.25, 95% [CI 0.05-0.86]), while HI was not. Conclusion: Our results indicate that HI is associated with stroke severity, cardiovascular risk factors and thrombolysis. PH is a rare complication, more frequent in severe stroke and with thrombolysis. In contrast to HI, PH is associated with worse functional outcome. The impact of HT after MRI-guided intravenous alteplase for unknown onset stroke on clinical outcome is similar as in the trials of stroke thrombolysis within a known early time-window., (Copyright © 2020 Jensen, Schlemm, Cheng, Lettow, Quandt, Boutitie, Ebinger, Endres, Fiebach, Fiehler, Galinovic, Thijs, Lemmens, Muir, Nighoghossian, Pedraza, Simonsen, Gerloff and Thomalla.)

Background: Thrombus fragmentation causing distal emboli is a feared complication during mechanical thrombectomy (MT). We aimed to investigate the impact of procedural parameters and thrombus properties on the incidence of peripheral emboli after MT for large vessel occlusions (LVO). Methods: We performed a prospective analysis of patients with LVO stroke successfully treated with MT, defined as a score of 2b, 2c, or 3 on the thrombolysis in cerebral infarction (TICI) scale. A follow-up MRI including high-resolution diffusion-weighted imaging (DWI) was performed within 24 h following MT. The primary endpoint was the number and volume of peripheral emboli, classified as punctuate DWI lesions distant to the diffusion-restricted core lesion. Further analysis included the influence of baseline characteristics, procedural and outcome parameters, and thrombus properties on peripheral emboli. Results: Thirty-seven patients with successful MT met the inclusion criteria. Use of a balloon guide catheter (BGC) and TICI were the only independent predictors for a reduced number of peripheral emboli. The use of a BGC led to a significant reduction in the number and volume of peripheral emboli, with a median number/volume of peripheral emboli of 4.5/287 μl (IQR 1.25-8.25/76-569 μl) vs. 12/938 μl (IQR 4-19/242-1,836 μl). In cases where BGC was not employed, the number of peripheral emboli increased with decreasing TICI scores. Conclusions: BGC-aided MT reduces the number of peripheral emboli in successful but incomplete reperfusion (TICI 2b and 2c). The effectiveness of this strategy therefore goes above and beyond that which can be demonstrated by the TICI score alone., (Copyright © 2020 Schönfeld, Kabiri, Kniep, Meyer, McDonough, Sedlacik, Ernst, Broocks, Faizy, Schön, Cheng, Thomalla, Fiehler and Hanning.)

Background: Diagnosis of primary angiitis of the central nervous system (PACNS) and discrimination of PACNS from its mimics, e. g., reversible cerebral vasoconstriction syndrome (RCVS) or moyamoya disease (MMD) as non-inflammatory vasculopathies, still remain challenging. Circulating endothelial cells (CEC) are well-established markers for endothelial damage and potential biomarkers in PACNS. This study aimed to investigate if CECs may also help to distinguish an active PACNS from its important differentials (RCVS, MMD). Methods: CECs were assessed in 47 subjects. Twenty-seven patients with PACNS were included, seven with an active disease (aPACNS), 20 in remission (rPACNS). Seven patients with RCVS/MMD were analyzed. Thirteen healthy subjects served as controls (HC). CECs were measured by immunomagnetic isolation from peripheral venous blood. Mann-Whitney- U -Tests were applied for between-group comparisons. The Benjamini-Hochberg-procedure was applied to adjust for multiple comparisons. Results: In aPACNS, CECs were significantly elevated compared to HC (480 vs. 40 CEC/ml, p < 0.001) and rPACNS (54 CEC/ml, p < 0.001). RCVS/MMD patients showed higher CEC levels (288 CEC/ml) than HC ( p < 0.001), but lower than those in aPACNS ( p = 0.017). An adjustment for multiple comparisons confirmed prior significant differences. An increased CEC value (cut-off 294 CEC/ml) is indicative for an active PACNS [sensitivity 100%, 95% confidence interval (CI) 63-100%; specificity 93%, CI 81-98%]. Conclusions: CECs may serve as biomarkers for diagnosis, treatment monitoring, and also for differential diagnosis of PACNS. CECs seem to be a marker of endothelial injury with higher levels in inflammatory than non-inflammatory vasculopathies. Larger patient samples are required to corroborate these findings., (Copyright © 2020 Deb-Chatterji, Pinnschmidt, Duan, Haeussler, Rissiek, Gerloff, Thomalla and Magnus.)

Background and Purpose: Recently, acute intracranial stenting (ICS) has gained more interest as a potential bailout strategy for large vessel occlusions (LVO) that are refractory to thrombectomy. However, there are currently no reports on ICS in patients with moderately severe stroke discussing the question if implementing a permanent stent is feasible and leads to improved recanalization after failed thrombectomy. Methods: We analyzed a large multicenter database of patients receiving ICS for anterior circulation LVO after failed thrombectomy. Inclusion criteria were defined as: Moderately severe stroke (National Institute Health Stroke Scale (NIHSS) ≤9 on admission), anterior circulation LVO, acute ICS after failed stent retriever MT. Primary endpoint was the rate of improved successful recanalization after ICS defined as a modified Thrombolysis In cerebral Infarction (mTICI) score≥2b. Favorable neurological outcome was defined as an early neurological improvement (ENI) of 4 points or reaching 0 with respect to baseline NIHSS. Results: Forty-one patients met the inclusion criteria. A median of 2 retrievals were performed (IQR 1-4) prior decision-making for ICS. ICS led in 90.2% (37/41) of cases to a final mTICI≥2b with significant improvement ( p < 0.001) after the last retrieval attempt. The median NIHSS decreased ( p = 0.178) from 7 (IQR 3.5-8) on admission to 2.5 (IQR 0-8.25) at discharge. ENI was observed in 47.4% (18/38). sICH occurred in 4.8% (2/41). Conclusion: ICS after failed thrombectomy appears to effectively improve recanalization rates in patients with moderately severe strokes. Thus, ICS should be considered also for patients with baseline NIHSS ≤9 if thrombectomy fails., (Copyright © 2020 Meyer, Fiehler, Thomalla, Krause, Lowens, Rothaupt, Kim, Heo, Yeo, Andersson, Kabbasch, Dorn, Chapot, Stracke and Hanning.)

Background: The "smoking paradox" indicates that patients with acute ischemic stroke (AIS) who smoke at the time of their stroke may have a better prognosis after intravenous thrombolysis than non-smokers. However, findings are inconsistent and data analyzing the effect of smoking on treatment efficacy of intravenous thrombolysis are scarce. Methods: We performed a pre-specified post-hoc subgroup analysis of the Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke (WAKE-UP) trial that randomized AIS patients with unknown time of symptom onset who had diffusion-weighted imaging-fluid attenuation inversion recovery (DWI-FLAIR) mismatch to either alteplase or placebo. Patients were categorized as current smokers or non-smokers (including former smokers and never-smokers). Baseline demographic and clinical characteristics, as well as clinical and imaging follow-up data were analyzed according to smoking status. Results: Four hundred and eighty six patients were included in the analysis. Current smokers (133, 27.4%) were younger (60.1 ± 13.0 vs. 67.2 ± 10.3 years; p < 0.001) and less often had arterial hypertension (45.0% vs. 56.8%; p = 0.02) or atrial fibrillation (3.8% vs. 15.3%; p < 0.001). The acute stroke presentation was more often due to large vessel occlusion among current smokers (27.1 vs. 16.2%; p = 0.01), and smokers had a trend towards more severe strokes (National Institutes of Health Stroke Scale score>10 in 27.1% vs. 19.5%; p = 0.08). The treatment effect of alteplase, quantified as odds ratio for a favorable outcome (modified Rankin Scale [mRS] score at 90 days of 0 or 1), did not differ between current smokers and non-smokers ( p -value for interaction: 0.59). After adjustment for age and stroke severity, neither the proportion of patients with favorable outcome, nor the median mRS score at 90 days differed between current smokers and non-smokers. When additional potential confounders were included in the model, the median mRS score was higher in current smokers than in non-smokers (cOR of better outcome for current smokers vs. non-smokers: 0.664 [0.451-0.978], p = 0.04). Conclusions: In patients with mild to moderate MRI-proven AIS and unknown time of symptom onset with DWI-FLAIR mismatch, current smokers had worse functional outcome as compared to non-smokers. Current smoking did not modify the treatment effect of alteplase. Clinical Trial registration: Main trial (WAKE-UP): ClinicalTrials.gov, NCT01525290; and EudraCT, 2011-005906-32. Registered 02 February 2012., (Copyright © 2019 Schlemm, Kufner, Boutitie, Nave, Gerloff, Thomalla, Simonsen, Ford, Lemmens, Muir, Nighoghossian, Pedraza, Ebinger and Endres.)

Introduction: In WAKE-UP (Efficacy and Safety of MRI-based Thrombolysis in Wake-Up Stroke), patients with an acute stroke of unknown onset time were randomized to treatment with intravenous alteplase or placebo, guided by MRI. Methods: In this exploratory post-hoc secondary analysis we compared clinical and imaging data, as well as treatment effects and safety of intravenous thrombolysis between patients with infra- vs. supratentorial stroke. Results: Forty-eight out of 503 randomized patients (9.5%) presented with a stroke involving the cerebellum or brainstem. Patients with infratentorial stroke were younger compared to patients with supratentorial stroke (mean age 60 vs. 66 years), more frequently male (85 vs. 62%), and less severely affected (median NIHSS 4.5 vs. 6.0). There was no heterogeneity for treatment effect between supratentorial (OR 1.67 95% CI 1.11-2.51) and infratentorial (OR 1.31 95% CI 0.41-4.22) sub-groups (test for interaction p = 0.70). In patients with infratentorial stroke, favorable outcome [a score of 0-1 on the modified Rankin scale (mRS) at 90 days] was observed in 12/22 patients (54.5%) in the alteplase group and in 13/25 patients (52.0%) in the placebo group ( p = 0.59). The primary safety endpoint (death or mRS 4-6 at day 90) occurred in three patients of the alteplase group (13.6%) and three patients in the placebo group (12.0%); p = 0.74. Discussion: WAKE-UP was underpowered for demonstrating treatment effect in subgroup analyses however, based on our current results, there is no evidence to recommend withholding MRI-guided thrombolysis in patients with unknown onset stroke of infratentorial localization., (Copyright © 2019 Galinovic, Boutitie, Fiebach, Villringer, Cheng, Ebinger, Endres, Fiehler, Ford, Thijs, Lemmens, Muir, Nighoghossian, Pedraza, Simonsen, Roy, Gerloff and Thomalla.)

Primary angiitis of the central nervous system (PACNS) is an inflammatory brain disease affecting the medium and small vessels of the CNS. Although recent data of patients with PACNS have advanced the understanding of the disease, the diagnosis remains challenging. Clinical presentation of PACNS is broad and unspecific and the majority of the diagnostic approaches are hallmarked by a low specificity. Thus, PACNS is commonly misdiagnosed. In addition, due to its potential aggressive course which may be altered by an adequate immunosuppressive treatment, delineation from other vasculopathies and PACNS mimics is crucial. New diagnostic tools and biomarkers which increase specificity and facilitate the diagnosis for patients with suspected PACNS are highly desirable. This short review summarizes the current procedures within the diagnostic process and aims to illustrate its difficulties and challenges. Furthermore, it highlights emerging biomarkers in the cerebrospinal fluid and peripheral venous blood as well as novel potential imaging tools that may corroborate the diagnosis. With new imaging techniques and a panel of biomarkers the certainty of the diagnosis may be increased and diagnostic processes more accelerated in the future.

Background and Purpose: Intracranial hemorrhage (ICH) remains a major complication of endovascular treatment (ET) in acute stroke. The aim of this study was to identify clinical and imaging predictors for ICH in patients with acute ischemic stroke undergoing successful ET. Methods: We performed a retrospective analysis of patients with large vessel occlusion in the anterior circulation who underwent successful ET at our university medical center between 2015 and 2018. ICH was diagnosed on non-enhanced CT and a binary outcome was defined: ICH occurrence in the immediate post-interventional phase within 12-36 h (yes/no). The impacts of clinical, radiological, and interventional parameters on outcome were assessed in logistic regression models. Results: One hundred and seven patients fulfilled the inclusion criteria. 37 (34.6%) showed an ICH of which 7 (6.5%) patients were diagnosed as symptomatic and 30 (28.04%) as asymptomatic. Multivariable regression analyses identified a lower ASPECTS (adjusted odds ratio (OR) 1.95, 95%CI: 1.4-3.63, P = 0.037), low collateral score (adjusted OR 0.12, 95%CI: 0.03-0.49, P = 0.003) and high Net Water Uptake (NWU) (adjusted OR 1.56, 95%CI: 2.34-1.03, P = 0.007) as independent predictors of ICH after successful ET. Conclusions: CT-based quantitative NWU, ASPECTS, and collateral score mediate tissue vulnerability and are reliable independent predictors of a bleeding event after successful ET. This imaging-based prediction model might be useful for early stratification of patients at high risk of a bleeding event after ET, especially with low ASPECTS.

Robust and reliable stroke lesion segmentation is a crucial step toward employing lesion volume as an independent endpoint for randomized trials. The aim of this work was to develop and evaluate a novel method to segment sub-acute ischemic stroke lesions from fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) datasets. After preprocessing of the datasets, a Bayesian technique based on Gabor textures extracted from the FLAIR signal intensities is utilized to generate a first estimate of the lesion segmentation. Using this initial segmentation, a customized voxel-level Markov random field model based on intensity as well as Gabor texture features is employed to refine the stroke lesion segmentation. The proposed method was developed and evaluated based on 151 multi-center datasets from three different databases using a leave-one-patient-out validation approach. The comparison of the automatically segmented stroke lesions with manual ground truth segmentation revealed an average Dice coefficient of 0.582, which is in the upper range of previously presented lesion segmentation methods using multi-modal MRI datasets. Furthermore, the results obtained by the proposed technique are superior compared to the results obtained by two methods based on convolutional neural networks and three phase level-sets, respectively, which performed best in the ISLES 2015 challenge using multi-modal imaging datasets. The results of the quantitative evaluation suggest that the proposed method leads to robust lesion segmentation results using FLAIR MRI datasets only as a follow-up sequence.

Background and Purpose: The immediate decrease of the apparent diffusion coefficient (ADC) is the main characteristic change of water diffusion in acute ischemic stroke. There is only limited information on the time course of diffusion parameters in different tissue compartments of cerebral ischemia. Materials and Methods: In a longitudinal study, we examined 21 patients with acute ischemic stroke by diffusion tensor imaging within 5 h after symptom onset, 3 h later, 2 days, and 1 month after symptom onset. Acute diffusion lesion and the fluid-attenuated inversion recovery (FLAIR) after 2 days were used as volumes of interest to define persistent core, lesion growth, and reversible acute diffusion lesion. For all diffusion parameters ratios between the stroke lesion VOIs and the mirror VOIs were calculated for each time point. ADC ratio, fractional anisotropy ratios, and eigenvalues ratios were measured in these volumes of interest and in contralateral mirror regions at each time points. Results: In the persistent core, ADC ratio (0.772) and all eigenvalues ratios were reduced on admission up to 1 day after stroke and increased after 1 month (ADC ratio 1.067). Within the region of infarct growth time course of diffusion parameter changes was similar, but delayed. In the brain area with reversible diffusion lesion, a partial normalization of diffusion parameters over the time was observed, while after 1 month diffusion parameters did not show the signature of healthy brain tissue. There were significantly different trends for all parameters over time between the three tissue compartments. Conclusion: Diffusion tensor imaging displays characteristic changes of water diffusion in different tissue compartments over time in acute ischemic stroke. Even regions with reversible diffusion lesion show diffusion signatures of persisting tissue alterations.

Structural brain imaging has continuously furthered our knowledge how different pathways of the human motor system contribute to residual motor output in stroke patients. Tract-related microstructure of pathways between primary and premotor areas has been found to critically influence motor output. The motor network is not restricted in connectivity to motor and premotor areas but these brain regions are densely interconnected with prefrontal regions such as the dorsolateral (DLPFC) and ventrolateral (VLPFC) prefrontal cortex. So far, the available data about the topography of such direct pathways and their microstructural properties in humans are sparse. To what extent prefrontal-premotor connections might also relate to residual motor outcome after stroke is still an open question. The present study was designed to address this issue of structural connectivity of prefrontal-premotor pathways in 26 healthy, older participants (66 ± 10 years old, 15 male) and 30 well-recovered chronic stroke patients (64 ± 10 years old, 21 males). Probabilistic tractography was used to reconstruct direct fiber tracts between DLPFC and VLPFC and three premotor areas (dorsal and ventral premotor cortex and the supplementary motor area). Direct connections between DLPFC/VLPFC and the primary motor cortex were also tested. Tract-related microstructure was estimated for each specific tract by means of fractional anisotropy and alternative diffusion metrics. These measures were compared between the groups and related to residual motor outcome in the stroke patients. Direct prefrontal-premotor trajectories were successfully traceable in both groups. Similar in gross anatomic topography, stroke patients presented only marginal microstructural alterations of these tracts, predominantly of the affected hemisphere. However, there was no clear evidence for a significant association between tract-related microstructure of prefrontal-premotor connections and residual motor functions in the present group of well-recovered stroke patients. Direct prefrontal-motor connections between DLPFC/VLPFC and the primary motor cortex could not be reconstructed in the present healthy participants and stroke patients.

Background: The aim of this prospective study was to investigate clinical deficits of patients with isolated cerebellar stroke applying a dedicated clinical score, the modified International Cooperative Ataxia Rating Scale (MICARS) and identifying factors that influence recovery. Methods: Fifteen patients with acute isolated cerebellar stroke received a standard stroke MRI on the day of admission and were clinically assessed using the mRS, NIHSS and the modified International Cooperative Ataxia Rating Scale (MICARS) on day 1, 3, 7, 30, and 90. A generalized linear model for repeated measures was employed to analyze the effect of stroke lesion location, volume, days after stroke, patient age, and MICARS score at admission on the total MICARS score. Results: Median patient age was 54 years, lesion location in most cases was right (87%) and in the PICA territory (11/15). Median lesion volume was 3.2 ml. Median NIHSS was 1. The median MICARS decreased from on day 1 with 23-4 at day 90. The generalized linear model identified MICARS score at day 1, lesion location, days after admission and the interaction of the last two on the total MICARS score, whereas there was no significant effect of stroke volume or patient age. Conclusions: Isolated cerebellar stroke can present with low NIHSS while more specific scales like the MICARS indicate a severe deficit. Patient age at onset of stroke and lesion volume had no significant effect on recovery from cerebellar symptoms as opposed to severity of symptoms at admission and lesion location.

Stroke is the second most common cause of death worldwide, responsible for 6.24 million deaths in 2015 (about 11% of all deaths). Three out of four stroke survivors suffer long term disability, as many cannot return to their prior employment or live independently. Eighty-seven percent of strokes are ischemic. As an increasing volume of ischemic brain tissue proceeds to permanent infarction in the hours following the onset, immediate treatment is pivotal to increase the likelihood of good clinical outcome for the patient. Triaging stroke patients for active therapy requires assessment of the volume of salvageable and irreversible damaged tissue, respectively. With Magnetic Resonance Imaging (MRI), diffusion-weighted imaging is commonly used to assess the extent of permanently damaged tissue, the core lesion. To speed up and standardize decision-making in acute stroke management we present a fully automated algorithm, ATLAS, for delineating the core lesion. We compare performance to widely used threshold based methodology, as well as a recently proposed state-of-the-art algorithm: COMBAT Stroke. ATLAS is a machine learning algorithm trained to match the lesion delineation by human experts. The algorithm utilizes decision trees along with spatial pre- and post-regularization to outline the lesion. As input data the algorithm takes images from 108 patients with acute anterior circulation stroke from the I-Know multicenter study. We divided the data into training and test data using leave-one-out cross validation to assess performance in independent patients. Performance was quantified by the Dice index. The median Dice coefficient of ATLAS algorithm was 0.6122, which was significantly higher than COMBAT Stroke, with a median Dice coefficient of 0.5636 ( p < 0.0001) and the best possible performing methods based on thresholding of the diffusion weighted images (median Dice coefficient: 0.3951) or the apparent diffusion coefficient (median Dice coefficeint: 0.2839). Furthermore, the volume of the ATLAS segmentation was compared to the volume of the expert segmentation, yielding a standard deviation of the residuals of 10.25 ml compared to 17.53 ml for COMBAT Stroke. Since accurate quantification of the volume of permanently damaged tissue is essential in acute stroke patients, ATLAS may contribute to more optimal patient triaging for active or supportive therapy.

Background and Aims: Assessment of ischemic lesions on computed tomography or MRI diffusion-weighted imaging (DWI) using the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is widely used to guide acute stroke treatment. However, it has never been defined how many voxels need to be affected to label a DWI-ASPECTS region ischemic. We aimed to assess the effect of various lesion load thresholds on DWI-ASPECTS and compare this automated analysis with visual rating., Materials and Methods: We analyzed overlap of individual DWI lesions of 315 patients from the previously published predictive value of fluid-attenuated inversion recovery study with a probabilistic ASPECTS template derived from 221 CT images. We applied multiple lesion load thresholds per DWI-ASPECTS region (>0, >1, >10, and >20% in each DWI-ASPECTS region) to compute DWI-ASPECTS for each patient and compared the results to visual reading by an experienced stroke neurologist., Results: By visual rating, median ASPECTS was 9, 84 patients had a DWI-ASPECTS score ≤7. Mean DWI lesion volume was 22.1 (±35) ml. In contrast, by use of >0, >1-, >10-, and >20%-thresholds, median DWI-ASPECTS was 1, 5, 8, and 10; 97.1% (306), 72.7% (229), 41% (129), and 25.7% (81) had DWI-ASPECTS ≤7, respectively. Overall agreement between automated assessment and visual rating was low for every threshold used (>0%: κ w  = 0.020 1%: κ w  = 0.151; 10%: κ w  = 0.386; 20% κ w  = 0.381). Agreement for dichotomized DWI-ASPECTS ranged from fair to substantial (≤7: >10% κ = 0.48; >20% κ = 0.45; ≤5: >10% κ = 0.528; and >20% κ = 0.695)., Conclusion: Overall agreement between automated and the standard used visual scoring is low regardless of the lesion load threshold used. However, dichotomized scoring achieved more comparable results. Varying lesion load thresholds had a critical impact on patient selection by ASPECTS. Of note, the relatively low lesion volume and lack of patients with large artery occlusion in our cohort may limit generalizability of these findings.

Post-stroke depression (PSD) affects approximately one-third of all stroke patients. It hinders rehabilitation and is associated with worse functional outcome and increased mortality. Since the identification of PSD is a significant clinical problem, clinicians and researchers have tried to identify predictors that indicate patients at risk of developing PSD. This also includes the research question whether there is an association between PSD and stroke lesion characteristics, e.g., lesion size and lesion location. Early studies addressing this question are largely limited by technical constraints and, thus, focused on simple lesion characteristics such as lesion side or proximity of the lesion to the frontal pole of the brain. More recent studies have addressed the impact of involvement of specific neuronal circuits in the stroke lesion. State-of-the-art methods of lesion symptom mapping to study PSD have only been applied to small patient samples. Overall, results are controversial and no clear pattern of stroke lesions associated with PSD has emerged, though there are findings suggesting that more frontal stroke lesions are associated with higher incidence of PSD. Available studies are hampered by methodological limitations, including drawbacks of lesion analysis methods, small sample size, and the issue of patient selection. These limitations together with differences in approaches to assess PSD and in methods of image analysis limit the comparability of results from different studies. To summarize, as of today no definite association between lesion location and PSD can be ascertained and the understanding of PSD rests incomplete. Further insights are expected from the use of modern lesion inference analysis methods in larger patient samples taking into account standardized assessment of possible confounding parameters, such as stroke treatment and reperfusion status.

Purpose: 18 F-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) is a promising new tool for the identification of inflammatory, infectious, and neoplastic foci. The aim of our work was to evaluate the diagnostic value of FDG-PET/CT in patients treated on a neurological/neurosurgical ICU or stroke unit., Methods: We performed a single-center, 10-year, retrospective evaluation of the value of FDG-PET/CT in critically ill adult patients with severe neurological disease., Results: 42 patients underwent FDG-PET/CT. Of these, 15 were ventilated and 10 were under vasopressor support. We identified four indications for performing FDG-PET/CT: (1) excluding a paraneoplastic etiology in an otherwise unexplained encephalitis, encephalopathy or neuropathy, (2) detecting a large-vessel vasculitis in patients with ischemic stroke, (3) detecting an infectious focus in sepsis, and less frequently (4) evaluating cerebral metabolism. In 22 patients who were evaluated for an unknown malignancy, 5 scans revealed either a previously unknown tumor or unknown metastases of a previously treated malignancy. Of 11 patients investigated for large-vessel vasculitis, 2 showed an inflammation of arteries supplying the brain. Of six sepsis cases, FDG-PET/CT identified an infectious focus in four., Summary: We found FDG-PET/CT to be a helpful tool in critically ill neurological patients. The results of the FDG-PET/CT had direct therapeutic consequences in the 12 true-positive cases. In 24 of the 29 negative cases, FDG-PET/CT helped exclude alternative diagnoses and/or influenced therapy. Our findings demonstrate the feasibility and diagnostic benefit of FDG-PET/CT in this group of patients.

Assessment of ischemic stroke lesions on computed tomography (CT) or MRI using the Alberta Stroke Program Early CT Score (ASPECTS) is widely used to guide acute stroke treatment. We aimed to review the current evidence on ASPECTS. Originally, the score was developed for standardized lesion assessment on non-contrast CT (NCCT). Early studies described ASPECTS as a predictor of functional outcome and symptomatic intracranial hemorrhage after iv-thrombolysis with a threshold of ≤7 suggested to identify patients at high risk. Following studies rather pointed toward a linear relationship between ASPECTS and functional outcome. ASPECTS has also been applied to assess perfusion CT and diffusion-weighted MRI (DWI). Cerebral blood volume ASPECTS proved to be the best predictor of outcome, outperforming NCCT-ASPECTS in some studies. For DWI-ASPECTS varying thresholds to identify patients at risk for poor outcome were reported. ASPECTS has been used for patient selection in three of the five groundbreaking trials proving efficacy of mechanical thrombectomy published in 2015. ASPECTS values predict functional outcome after thrombectomy. Moreover, treatment effect of thrombectomy appears to depend on ASPECTS values being smaller or not present in low ASPECTS, while patients with ASPECTS 5-10 do clearly benefit from mechanical thrombectomy. However, as patients with low ASPECTS values were excluded from recent trials data on this subgroup is limited. There are several limitations to ASPECTS addressed in a growing number of studies. The score is limited to the anterior circulation, the template is unequally weighed and correlation with lesion volume depends on lesion location. Overall ASPECTS is a useful and easily applicable tool for assessment of prognosis in acute stroke treatment and to help guide acute treatment decisions regardless whether MRI or CT is used. Patients with low ASPECTS values are unlikely to achieve good outcome. However, methodological constraints of ASPECTS have to be considered, and based on present data, a clear cutoff value to define "low ASPECTS values" cannot be given.

Purpose: The aim of this study was to investigate the impact of a coexisting internal carotid artery (ICA) stenosis on lesion volumes as well as diffusion and perfusion parameters in acute ischemic stroke resulting from middle cerebral artery (MCA) occlusion., Material and Methods: Magnetic resonance imaging data of 32 patients with MCA occlusion with or without additional ICA stenosis imaged within 4.5 h of symptom onset were analyzed. Both groups consisted of 16 patients. Acute diffusion lesions were semi-automatically segmented in apparent diffusion coefficient (ADC) MRI datasets. Perfusion maps of cerebral blood volume (CBV), cerebral blood flow, mean transit time and T max were calculated using perfusion-weighted MRI datasets. Tissue-at-risk (TAR) volumes were generated by subtracting the ADC lesion from the hypoperfusion lesion defined by T max >6 s. Median ADC and perfusion parameter values were extracted separately for the diffusion lesion and TAR and used for statistical analysis., Results: No significant differences were found between the groups regarding the diffusion lesion and TAR volumes. Statistical analysis of diffusion and perfusion parameters revealed CBV as the only parameter with a significant difference (p = 0.009) contributing a small effect (η(2) = 0.11) to the group comparison with higher CBV values for the patient group with a coexisting ICA stenosis, while no significant effects were found for the other diffusion and perfusion parameters analyzed., Conclusion: The results of this study suggest that a coexisting ICA stenosis does not have a strong effect on tissue status or perfusion parameters in acute stroke patients except for a moderate elevation of CBV. This may reflect improved collateral circulation or ischemic preconditioning in patients with a pre-existing proximal stenosis balancing impaired perfusion from the stenosis.

About 25% of all strokes occur during sleep, i.e., without knowledge of exact time of symptom onset. According to licensing criteria, this large group of patients is excluded from treatment with received tissue-plasminogen activator, the only specific stroke treatment proven effective in large randomized trials. This paper reviews clinical and imaging characteristics of wake-up stroke and gives an update on treatment options for these patients. From clinical and imaging studies, there is evidence suggesting that many wake-up strokes occur close to awakening and thus, patients might be within the approved time-window of thrombolysis when presenting to the emergency department. Several imaging approaches are suggested to identify wake-up stroke patients likely to benefit from thrombolysis, including non-contrast CT, CT-perfusion, penumbral MRI, and the recent concept of diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR). A number of small case series and observational studies report results of thrombolysis in wake-up stroke, and no safety concerns have occurred, while conclusions on efficacy cannot be drawn from these studies. To this end, there are ongoing clinical trials enrolling wake-up stroke patients based on imaging findings, i.e., the DWI-FLAIR-mismatch (WAKE-UP) or penumbral imaging (EXTEND). The results of these trials will provide evidence to guide thrombolysis in wake-up stroke and thus, expand treatment options for this large group of stroke patients.