Intravenous Thrombolysis Before Thrombectomy Improves Functional Outcome After Stroke Independent of Reperfusion Grade.

BACKGROUND: We studied the association of bridging intravenous thrombolysis (IVT) before thrombectomy for anterior circulation large-vessel occlusion and functional outcome and scrutinized its dependence on grade of reperfusion and distal thrombus migration. METHODS AND RESULTS: We included consecutive patients with anterior circulation large-vessel occlusion from our prospective registry of thrombectomy-eligible patients treated from January 1, 2017 to January 1, 2023 at a tertiary stroke center in Germany in this retrospective cohort study. To evaluate the association of bridging IVT and functional outcome quantified via modified Rankin Scale score at 90 days we used multivariable logistic and lasso regression including interaction terms with grade of reperfusion quantified via modified Thrombolysis in Cerebral Infarction (mTICI) scale and distal thrombus migration adjusted for demographic and cardiovascular risk profiles, clinical and imaging stroke characteristics, onset-to-recanalization time and distal thrombus migration. We performed sensitivity analysis using propensity score matching. In our study population of 1000 thrombectomy-eligible patients (513 women; median age, 77 years [interquartile range, 67-84]), IVT emerged as a predictor of favorable functional outcome (modified Rankin Scale score, 0-2) independent of modified mTICI score (adjusted odds ratio, 0.49 [95% CI, 0.32-0.75]; P=0.001). In those who underwent thrombectomy (n=812), the association of IVT and favorable functional outcome was reproduced (adjusted odds ratio, 0.49 [95% CI, 0.31-0.74]; P=0.001) and was further confirmed on propensity score analysis, where IVT led to a 0.35-point decrease in 90-day modified Rankin Scale score (ß=-0.35 [95 CI%, -0.68 to 0.01]; P=0.04). The additive benefit of IVT remained independent of modified mTICI score (ß=-1.79 [95% CI, -3.43 to -0.15]; P=0.03) and distal thrombus migration (ß=-0.41 [95% CI, -0.69 to -0.13]; P=0.004) on interaction analysis. Consequently, IVT showed an additive association with functional outcome in the subpopulation of patients undergoing thrombectomy who achieved successful reperfusion (mTICI ≥2b; ß=-0.46 [95% CI, -0.74 to -0.17]; P=0.002) and remained beneficial in those with unsuccessful reperfusion (mTICI ≤2a; ß=-0.47 [95% CI, -0.96 to 0.01]; P=0.05). CONCLUSIONS: In thrombectomy-eligible patients with anterior circulation large-vessel occlusion, IVT improves functional outcome independent of grade of reperfusion and distal thrombus migration.

Intravenous Thrombolysis by Telestroke in the 3- to 4.5-h Time Window.

Background: While intravenous thrombolysis (IVT) in ischemic stroke can be safely applied in telestroke networks within 3 h from symptom onset, there is a lack of evidence for safety in the expanded 3- to 4. 5-h time window. We assessed the safety and short-term efficacy of IVT in acute ischemic stroke (AIS) in the expanded time window delivered through a hub-and-spoke telestroke network. Methods: Observational study of patients with AIS who received IVT at the Stroke Eastern Saxony Telemedical Network between 01/2014 and 12/2015. We compared safety data including symptomatic intracerebral hemorrhage (sICH; according to European Cooperative Acute Stroke Study II definition) and any intracerebral hemorrhage (ICH) between patients admitted to telestroke spoke sites and patients directly admitted to a tertiary stroke center representing the hub of the network. We also assessed short-term efficacy data including favorable functional outcome (i.e., modified Rankin Scale ≤ 2) and National Institutes of Health Stroke Scale (NIHSS) at discharge, hospital discharge disposition, and in-hospital mortality. Results: In total, 152 patients with AIS were treated with IVT in the expanded time window [spoke sites, n = 104 (26.9%); hub site, n = 48 (25.9%)]. Patients treated at spoke sites had less frequently a large vessel occlusion [8/104 (7.7) vs. 20/48 (41.7%); p < 0.0001], a determined stroke etiology (p < 0.0001) and had slightly shorter onset-to-treatment times [210 (45) vs. 228 (58) min; p = 0.02] than patients who presented to the hub site. Both cohorts did not display any further differences in demographics, vascular risk factors, median baseline NIHSS scores, or median baseline Alberta stroke program early CT score (p > 0.05). There was no difference in the frequency of sICH (4.9 vs. 6.3%; p = 0.71) or any ICH (8.7 vs. 16.7%; p = 0.15). Neither there was a difference regarding favorable functional outcome (44.1 vs. 39.6%; p = 0.6) nor median NIHSS [3 (5.5) vs. 2.5 (5.75); p = 0.92] at discharge, hospital discharge disposition (p = 0.28), or in-hospital mortality (9.6 vs. 8.3%; p = 1.0). Multivariable modeling did not reveal an association between telestroke and sICH or favorable functional outcome (p > 0.05). Conclusions: Delivery of IVT in the expanded 3- to 4.5-h time window through a telestroke network appears to be safe with equivalent short-term functional outcomes for spoke-and-hub center admissions.

Impact of the coronavirus disease 2019 pandemic on stroke teleconsultations in Germany in the first half of 2020.

BACKGROUND AND PURPOSE: The effects of the coronavirus disease 2019 (COVID-19) pandemic on telemedical care have not been described on a national level. Thus, we investigated the medical stroke treatment situation before, during, and after the first lockdown in Germany. METHODS: In this nationwide, multicenter study, data from 14 telemedical networks including 31 network centers and 155 spoke hospitals covering large parts of Germany were analyzed regarding patients' characteristics, stroke type/severity, and acute stroke treatment. A survey focusing on potential shortcomings of in-hospital and (telemedical) stroke care during the pandemic was conducted. RESULTS: Between January 2018 and June 2020, 67,033 telemedical consultations and 38,895 telemedical stroke consultations were conducted. A significant decline of telemedical (p < 0.001) and telemedical stroke consultations (p < 0.001) during the lockdown in March/April 2020 and a reciprocal increase after relaxation of COVID-19 measures in May/June 2020 were observed. Compared to 2018-2019, neither stroke patients' age (p = 0.38), gender (p = 0.44), nor severity of ischemic stroke (p = 0.32) differed in March/April 2020. Whereas the proportion of ischemic stroke patients for whom endovascular treatment (14.3% vs. 14.6%; p = 0.85) was recommended remained stable, there was a nonsignificant trend toward a lower proportion of recommendation of intravenous thrombolysis during the lockdown (19.0% vs. 22.1%; p = 0.052). Despite the majority of participating network centers treating patients with COVID-19, there were no relevant shortcomings reported regarding in-hospital stroke treatment or telemedical stroke care. CONCLUSIONS: Telemedical stroke care in Germany was able to provide full service despite the COVID-19 pandemic, but telemedical consultations declined abruptly during the lockdown period and normalized after relaxation of COVID-19 measures in Germany.

Endovascular therapy for anterior circulation large vessel occlusion in telestroke.

INTRODUCTION: Recent exploratory analysis suggested comparable outcomes among stroke patients undergoing endovascular therapy (EVT) for anterior circulation large vessel occlusion, whether selected via the telestroke network or admitted directly to an EVT-capable centre. We further studied the role of telemedicine in selection of ischaemic stroke patients potentially eligible for EVT. METHODS: We prospectively included consecutive ischaemic stroke patients with anterior circulation large vessel occlusion who underwent EVT at our neurovascular centre (January 2016 to March 2018). We compared safety and efficacy including symptomatic intracerebral haemorrhage (sICH), successful reperfusion (mTICI 2b/3), 90-day favourable outcome (mRS ≤ 2) and 90-day survival between patients transferred from telestroke hospitals and patients directly admitted. RESULTS: Of 280 potentially EVT-eligible patients, 72/129 (56%) telestroke and 91/151 (60%) direct admissions eventually underwent EVT (age 76 (66-82) years, median (interquartile range), 46% men, NIHSS score 17 (13-20)). Telestroke patients had larger pre-EVT infarct cores (ASPECTS: 7 (6-8) vs. 8 (7-9); p < 0.0001) and shorter door-to-groin puncture times (71 (56-84) vs. 101 (79-133) min; p < 0.0001) than directly admitted patients. sICH (2.8% vs. 1.1%; p = 0.58), successful reperfusion (81% vs. 77%; p = 0.56), 90-day favourable outcome (25% vs. 29%; p = 0.65) and 90-day survival (73% vs. 67%; p = 0.39) rates were comparable among telestroke and direct admissions. DISCUSSION: Our data underpins the important role of telemedicine in identifying acute ischaemic stroke patients lacking immediate access to EVT-capable stroke centres. Stroke patients selected via telemedicine and those directly admitted had comparable chances of favourable outcomes after EVT for large vessel occlusion.

Acute endovascular treatment delivery to ischemic stroke patients transferred within a telestroke network: a retrospective observational study.

Background Five randomized controlled trials recently demonstrated efficacy of endovascular treatment in acute ischemic stroke. Telestroke networks can improve stroke care in rural areas but their role in patients undergoing endovascular treatment is unknown. Aim We compared clinical outcomes of endovascular treatment between anterior circulation stroke patients transferred after teleconsultation and those directly admitted to a tertiary stroke center. Methods Data derived from consecutive patients with intracranial large vessel occlusion who underwent endovascular treatment from January 2010 to December 2014 at our tertiary stroke center. We compared baseline characteristics, onset-to-treatment times, symptomatic intracranial hemorrhage, in-hospital mortality, reperfusion (modified Treatment in Cerebral Infarction 2b/3), and favorable functional outcome (modified Rankin scale ≤ 2) at discharge between patients transferred from spoke hospitals and those directly admitted. Results We studied 151 patients who underwent emergent endovascular treatment for anterior circulation stroke: median age 70 years (interquartile range, 62-75); 55% men; median National Institutes of Health Stroke Scale score 15 (12-20). Of these, 48 (31.8%) patients were transferred after teleconsultation and 103 (68.2%) were primarily admitted to our emergency department. Transferred patients were younger (p = 0.020), received more frequently intravenous tissue plasminogen activator (p = 0.008), had prolonged time from stroke onset to endovascular treatment initiation (p < 0.0001) and tended to have lower rates of symptomatic intracranial hemorrhage (4.2% vs. 11.7%; p = 0.227) and mortality (8.3% vs. 22.6%; p = 0.041) than directly admitted patients. Similar rates of reperfusion (56.2% vs. 61.2%; p = 0.567) and favorable functional outcome (18.8% vs. 13.7%; p = 0.470) were observed in telestroke patients and those who were directly admitted. Conclusions Telestroke networks may enable delivery of endovascular treatment to selected ischemic stroke patients transferred from remote hospitals that is equitable to patients admitted directly to tertiary hospitals.

Telemedical Brain Computed Tomography Misinterpretation by Stroke Neurologists Is Not Associated with Thrombolysis-Related Intracranial Hemorrhage.

BACKGROUND: The Stroke Eastern Saxony Network (SOS-NET) provides telecare for acute stroke patients. Stroke neurologists recommend intravenous thrombolysis based on clinical assessment and cerebral computed tomography (CT) evaluation using Alberta Stroke Program Early CT score (ASPECTS). We sought to assess whether ASPECTS misinterpretation by stroke neurologists was associated with thrombolysis-related symptomatic intracranial hemorrhage (sICH). METHODS: We retrospectively analyzed consecutive SOS-NET patients treated with thrombolytics from July 2007 to July 2012. Experienced neuroradiologists re-evaluated CT scans blinded to clinical information providing reference standard. We defined ASPECTS underestimation as ASPECTS stroke neurologist--ASPECTS neuroradiologist more than 1 point. Primary outcome was sICH by European Cooperative Acute Stroke Study II criteria. Secondary outcome was unfavorable outcome at discharge defined as modified Rankin Scale scores 3 or more. RESULTS: Of 1659 patients with acute ischemic stroke, thrombolysis was performed in 657 patients. Complete primary outcome and imaging data were available for 432 patients (median age, 75; interquartile range [IQR], 12 years; National Institutes of Health Stroke Scale score, 12 [IQR, 11]; 52.8% women). Nineteen patients (4.4%) had sICH, and 259 patients (60.0%) had an unfavorable outcome at discharge. Interobserver agreement between ASPECTS assessment was fair (κ = .51). ASPECTS underestimation was neither associated with sICH (adjusted odds ratio (OR), 1.32; 95% confidence interval (CI), .36-4.83, P = .68) nor unfavorable outcome (adjusted OR, 1.10; 95% CI, .47-2.54; P = .83). CONCLUSIONS: Despite fair interrater agreement between stroke neurologists and expert neuroradiologists, underestimation of ASPECTS by the former was not associated with thrombolysis-related sICH in our telestroke network.

Emergency transfer of acute stroke patients within the East Saxony telemedicine stroke network: a descriptive analysis.

BACKGROUND: Telemedicine may facilitate the selection of stroke patients who require emergency transfer to a comprehensive stroke center to receive additional therapies other than intravenous tissue plasminogen activator. AIMS AND/OR HYPOTHESIS: We sought to analyze frequency, patient characteristics, and specific therapies among emergently transferred patients within the telemedical Stroke East Saxony Network. METHODS: We reviewed consecutive patients who were transferred emergently from remote spoke sites to hub sites. Certified stroke neurologists performed teleconsultations 24/7, with access to high-speed videoconferencing and transfer of brain images. Emergent transfers were initiated when considered necessary by the stroke neurologist. RESULTS: In 2009 and 2010, we conducted 1413 teleconsultations and subsequently recommended transfer in 339 (24%) patients [mean age 64 ± 14 years, 54% males, median National Institutes of Health Stroke Scale score 5 (interquartile range, IQR 12). The mean teleconsultation-to-arrival time was 1·7 ± 0·8 h (median 1·6 h). Sixty-eight (20%) transferred patients had a nonstroke diagnosis. The remaining 271 (80%) patients had stroke diagnoses [ischemic stroke, 114 (34%); transient ischemic attack, 8 (2%); and intracranial haemorrhage, 149 (44%)]. Forty (35%) ischemic stroke patients received tissue plasminogen activator at spoke sites ('drip and ship'). Of the 240 stroke patients emergently transferred to the main hub site, 119 (49·6%) received at least one specific stroke therapy. CONCLUSIONS: A remarkable number of stroke patients can be transferred within a telemedical network to enable the delivery of specific stroke therapies that require advanced multispecialty expertise. Whether associated logistic efforts and costs have an impact on patients' clinical outcomes needs to be evaluated.

Reliability of brain CT evaluation by stroke neurologists in telemedicine.

OBJECTIVE: To determine the reliability and therapeutic impact of standardized cerebral CT evaluation and quantification of early ischemic changes (EIC) with the Alberta Stroke Program Early CT Score (ASPECTS) by stroke neurologists in the Stroke Eastern Saxony Network (SOS-NET), which provides telemedical consultations for patients with acute ischemic stroke. METHODS: Two neuroradiologists re-evaluated all CT scans of consecutive SOS-NET patients in 2009 blinded to clinical information providing reference standard. We defined discrepant CT findings as all false-positive or false-negative EIC and brain pathology findings and ASPECTS deviations >1 point. We subsequently discussed the clinical impact of discrepant CT findings unblinded to clinical information. Weighted kappa (κ(w)) statistic was used to determine the interobserver agreement for ASPECTS. RESULTS: Of 582 patients, complete imaging data were available for 536 patients (351 cerebral ischemic events, 105 primary intracranial hemorrhages, and 80 stroke mimics). The neuroradiologists detected discrepant CT findings in 43 patients (8.0%) that were rated as clinically relevant in 9 patients (1.7%). Stroke neurologists recommended IV thrombolysis in 8 patients despite extensive EIC (ASPECTS ≤5). One of these patients had symptomatic intracranial hemorrhage. In 1 nonthrombolyzed patient, the stroke neurologist missed subdural hematoma. The interobserver agreement on ASPECTS between stroke neurologists and expert readers was substantial (κ(w) = 0.62; 95% confidence interval 0.54-0.71). CONCLUSIONS: Clinically relevant misinterpretation of the CT scans was rare in our acute telestroke service. ASPECTS is a reliable tool to assess the extent of EIC by stroke neurologists in telemedicine in real time.

Human mesenchymal stem cell proliferation and osteogenic differentiation during long-term ex vivo cultivation is not age dependent.

Mesenchymal stem cells (MSCs) are of major clinical interest for the development of cell-based strategies to treat musculoskeletal diseases including critical-size bone defects caused by trauma, degenerative disorders, or infections. Elderly people mainly suffer from critical-size bone defects from the rising incidence of trauma, osteoporosis, and arthroplasties. In this study we investigated the influence of donor age on proliferation and osteogenic differentiation in long-term ex vivo cultures of primary human MSCs from patients in different age groups. Fifteen patients (8 men/7 women) comprised three age groups: (I) <50 years, (II) 50-65 years, and (III) >65 years. MSCs harvested from bone marrow derived from routine surgical procedures were isolated and cultured in standard medium over eight passages. Osteogenic differentiation was induced by dexamethasone (10 nM), ascorbic acid (300 µM), and ß-glycerophosphate (3.5 mM). Osteogenic differentiation capacity of MSCs was quantified by alkaline phosphatase (ALP) activity, fluorescence-activated cell sorting (FACS) analysis of the surface markers CD9, CD90, CD54, CD166, CD105, CD44, and CD73, and RT-PCR for Coll I and II, Cbfa 1, ALP, OC, BSP1, and GAPDH genes characterized the phenotypic changes during monolayer expansion. In vitro chondrogenic differentiation was analyzed by immunohistochemistry and RT-PCR. Progenitor cells could be expanded in the long term from all bone marrow donations. FACS single staining analysis from MSCs showed no significant difference between the age groups. The surface antigen CD166 was predominantly found in all cell cultures independently of differentiation stage. Comparison of expanded and differentiated MSCs within a single age group showed that undifferentiated MSCs had higher CD44 levels. Osteogenic stimulation of MSCs was confirmed by measuring ALP activity. The highest ALP activity was found in probands of the age group >65 years. Additionally, we observed a tendency toward male-specific ALP increase during differentiation. Osteogenic marker gene expression in MSCs was detected by RT-PCR. No significant expression differences were detected between the three donor age groups. Micromass culture of MSCs resulted histologically and immunohistologically in a chondrogenic phenotype. Elderly osteoprogenitor cell donors are a highly clinically relevant patient population. In summary, cultivation leads to a reduced osteogenic differentiation capacity regardless of age. Because donor age does not affect osteogenic differentiation potential, it should not be used as an exclusion criterion for autologous transplantation of human adult MSCs.