Golden Hour Intravenous Thrombolysis for Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

OBJECTIVES: The benefits of intravenous thrombolysis are time-dependent, with maximum efficacy when administered within the first "golden" hour after onset. Nevertheless, the impact of golden hour thrombolysis has not been well quantified. METHODS: Medline, Embase, and Web of Science databases were systematically searched from inception to August 27, 2023. We included studies that reported safety and efficacy outcomes of ischemic stroke patients treated with intravenous thrombolysis in the golden hour versus later treatment window. The primary outcome was an excellent functional outcome, defined as a modified Rankin Scale score of 0-1 at 90 days. The secondary efficacy outcome was a good functional outcome (defined as modified Rankin Scale score of 0-2). The main safety outcome was symptomatic intracerebral hemorrhage. RESULTS: Seven studies involving 78,826 patients met the selection criteria. Golden hour thrombolysis was associated with higher odds of 90-day excellent functional outcomes (OR 1.40, 95% CI 1.16-1.67) and 90-day good functional outcomes (OR 1.38, 95% CI 1.13-1.69) compared with thrombolysis outside the golden hour. The number needed to treat to benefit for golden hour thrombolysis to reduce disability by at least 1 level on the modified Rankin Scale per patient was 2.6. Rates of symptomatic intracerebral hemorrhage and mortality were similar between groups. INTERPRETATION: Golden hour thrombolysis significantly improved acute ischemic stroke outcomes. The findings provide rationale for intensive efforts aimed at expediting thrombolytic therapy within the golden hour window following the onset of acute ischemic stroke. ANN NEUROL 2024;96:582-590.

Endovascular Therapy for Stroke Due to Basilar-Artery Occlusion.

BACKGROUND: The effectiveness of endovascular therapy in patients with stroke caused by basilar-artery occlusion has not been well studied. METHODS: We randomly assigned patients within 6 hours after the estimated time of onset of a stroke due to basilar-artery occlusion, in a 1:1 ratio, to receive endovascular therapy or standard medical care. The primary outcome was a favorable functional outcome, defined as a score of 0 to 3 on the modified Rankin scale (range, 0 to 6, with 0 indicating no disability, 3 indicating moderate disability, and 6 indicating death) at 90 days. The primary safety outcomes were symptomatic intracranial hemorrhage within 3 days after the initiation of treatment and mortality at 90 days. RESULTS: A total of 300 patients were enrolled (154 in the endovascular therapy group and 146 in the medical care group). Intravenous thrombolysis was used in 78.6% of the patients in the endovascular group and in 79.5% of those in the medical group. Endovascular treatment was initiated at a median of 4.4 hours after stroke onset. A favorable functional outcome occurred in 68 of 154 patients (44.2%) in the endovascular group and 55 of 146 patients (37.7%) in the medical care group (risk ratio, 1.18; 95% confidence interval [CI], 0.92 to 1.50). Symptomatic intracranial hemorrhage occurred in 4.5% of the patients after endovascular therapy and in 0.7% of those after medical therapy (risk ratio, 6.9; 95% CI, 0.9 to 53.0); mortality at 90 days was 38.3% and 43.2%, respectively (risk ratio, 0.87; 95% CI, 0.68 to 1.12). CONCLUSIONS: Among patients with stroke from basilar-artery occlusion, endovascular therapy and medical therapy did not differ significantly with respect to a favorable functional outcome, but, as reflected by the wide confidence interval for the primary outcome, the results of this trial may not exclude a substantial benefit of endovascular therapy. Larger trials are needed to determine the efficacy and safety of endovascular therapy for basilar-artery occlusion. (Funded by the Dutch Heart Foundation and others; BASICS ClinicalTrials.gov number, NCT01717755; Netherlands Trial Register number, NL2500.).

Economic Evaluation of a Mobile Stroke Unit Service in Germany.

BACKGROUND: Lower global disability and higher quality of life among ischemic stroke patients was found to be associated with the dispatch of mobile stroke units (MSUs) among patients eligible for recanalizing treatments in the Berlin_Prehospital Or Usual Delivery of stroke care (B_PROUD) study. The current study assessed the cost-utility and cost-effectiveness of additional MSU dispatch using data from this prospective, controlled, intervention study. METHODS: Outcomes considered in the economic evaluation included quality-adjusted life years (QALYs) derived from the 3-level version of EQ-5D (EQ-5D-3L) and modified Rankin Scale (mRS) scores for functional outcomes 3-months after stroke. Costs were prospectively collected during the study by the MSU provider (Berlin Fire Brigade) and the B_PROUD research team. We focus our results on the societal perspective. As we aimed to determine the economic consequences of the intervention beyond the study's follow-up period, both care costs and QALYs were extrapolated over 5 years. RESULTS: The additional MSU dispatch resulted in an incremental €40,984 per QALY. The best-case scenario and the worst-case scenario yielded additional costs of, respectively, €24,470.76 and €61,690.88 per QALY. In the cost-effectiveness analysis, MSU dispatch resulted in incremental costs of €81,491 per survival without disability. The best-case scenario and the worst-case scenario yielded additional costs of, respectively, €44,455.30 and €116,491.15 per survival without disability. INTERPRETATION: Among patients eligible for recanalizing treatments in ischemic stroke, MSU dispatch was associated with both higher QALYs and higher costs and is cost-effective when considering internationally accepted thresholds ranging from an additional €40,000 to €80,000 per QALY. ANN NEUROL 2023;93:942-951.

Effect of Mobile Stroke Unit Dispatch in all Patients with Acute Stroke or TIA.

OBJECTIVE: To determine the effect of additional mobile stroke unit (MSU) dispatch on functional outcomes among the full spectrum of stroke patients, regardless of subtype or potential contraindications to reperfusion therapies. METHODS: We used data from the nonrandomized Berlin-based B_PROUD study (02/2017 to 05/2019), in which MSUs were dispatched based solely on availability, and the linked B-SPATIAL stroke registry. All patients with final stroke or transient ischemic attack (TIA) diagnoses were eligible. The intervention under study was the additional dispatch of an MSU, an emergency physician-staffed ambulance equipped to provide prehospital imaging and thrombolytic treatment, compared to conventional ambulance alone. The primary outcome was the 3-month modified Rankin Scale (mRS) score, and the co-primary outcome was a 3-tiered disability scale. We identified confounders using directed acyclic graphs and obtained adjusted effect estimates using inverse probability of treatment weighting. RESULTS: MSUs were dispatched to 1,125 patients (mean age: 74 years, 46.5% female), while for 1,141 patients only conventional ambulances were dispatched (75 years, 49.9% female). After confounding adjustment, MSU dispatch was associated with more favorable 3-month mRS scores (common odds ratio [cOR] = 0.82; 95% confidence interval [CI]: 0.71-0.94). No statistically significant association was found with the co-primary outcome (cOR = 0.86; 9% CI: 0.72-1.01) or 7-day mortality (OR = 0.94; 95% CI: 0.59-1.48). INTERPRETATION: When considering the entire population of stroke/TIA patients, MSU dispatch improved 3-month functional outcomes without evidence of compromised safety. Our results are relevant for decision-makers since stroke subtype and treatment eligibility are unknown at time of dispatch. ANN NEUROL 2023;93:50-63.

A Managed Care System with Telemedicine Support for Neurological Emergencies.

OBJECTIVES: Telemedicine is frequently used to provide remote neurological expertise for acute stroke workup and was associated with better functional outcomes when combined with a stroke unit system-of-care. We investigated whether such system-of-care yields additional benefits when implemented on top of neurological competence already available onsite. METHODS: Quality improvement measures were implemented within a "hub-and-spoke" teleneurology network in 11 hospitals already provided with onsite or telestroke expertise. Measures included dedicated units for neurological emergencies, standardization of procedures, multiprofessional training, and quality-of-care monitoring. Intervention effects were investigated in a controlled study enrolling patients insured at 3 participating statutory health insurances diagnosed with acute stroke or other neurological emergencies. Outcomes during the intervention period between November 2017 and February 2020 were compared with those pre-intervention between October 2014 and March 2017. To control for temporal trends, we compared outcomes of patients with respective diagnoses in 11 hospitals of the same region. Primary outcome was the composite of up-to-90-day death, new disability with the need of ambulatory or nursing home care, expressed by adjusted hazard ratio (aHR). RESULTS: We included 1,418 patients post-implementation (55% female, mean age 76.7 ± 12.8 year) and 2,306 patients pre-implementation (56%, 75.8 ± 13.0 year, respectively). The primary outcome occurred in 479/1,418 (33.8%) patients post-implementation and in 829/2,306 (35.9%) pre-implementation. The aHR for the primary outcome was 0.89 (95% confidence interval [CI]: 0.79-0.99, p = 0.04) with no improvement seen in non-participating hospitals between post- versus pre-implementation periods (aHR 1.04; 95% CI: 0.95-1.15). INTERPRETATION: Implementation of a multicomponent system-of-care was associated with a lower risk of poor outcomes. ANN NEUROL 2023;93:511-521.

Early Intubation in Endovascular Therapy for Basilar Artery Occlusion: A Post Hoc Analysis of the BASICS Trial.

BACKGROUND: The optimal anesthetic management for endovascular therapy (EVT) in patients with posterior circulation stroke remains unclear. Our objective was to investigate the impact of early intubation in patients enrolled in the BASICS trial (Basilar Artery International Cooperation Study). METHODS: BASICS was a multicenter, randomized, controlled trial that compared the efficacy of EVT compared with the best medical care alone in patients with basilar artery occlusion. In this post hoc analysis, early intubation within the first 24 hours of the estimated time of basilar artery occlusion was examined as an additional covariate using regression modeling. We estimated the adjusted relative risks (RRs) for favorable outcomes, defined as modified Rankin Scale scores of 0 to 3 at 90 days. An adjusted common odds ratio was estimated for a shift in the distribution of modified Rankin Scale scores at 90 days. RESULTS: Of 300 patients in BASICS, 289 patients were eligible for analysis (151 in the EVT group and 138 in the best medical care group). compared with medical care alone, EVT was related to a higher risk of early intubation (RR, 1.29 [95% CI, 1.09-1.53]; P<0.01), and early intubation was negatively associated with favorable outcome (RR, 0.61 [95% CI, 0.45-0.84]; P=0.002). Whereas there was no overall treatment effect of EVT on favorable outcome (RR, 1.22 [95% CI, 0.95-1.55]; P=0.121), EVT was associated with favorable outcome (RR, 1.34 [95% CI, 1.05-1.71]; P=0.018) and a shift toward lower modified Rankin Scale scores (adjusted common odds ratio, 1.63 [95% CI, 1.04-2.57]; P=0.033) if adjusted for early intubation. CONCLUSIONS: In this post hoc analysis of the neutral BASICS trial, early intubation was linked to unfavorable outcomes, which might mitigate a potential benefit from EVT by indirect effects due to an increased risk of early intubation. This relationship may be considered when assessing the efficacy of EVT in patients with basilar artery occlusion in future trials.

The Effect of Mobile Stroke Unit Care on Functional Outcomes: An Application of the Front-door Formula.

BACKGROUND: The Berlin-based B_PROUD study was designed to assess the effect of mobile stroke unit (MSU) dispatch among ischemic stroke and transient ischemic attack (TIA) patients without contraindications to reperfusion treatments. However, a large proportion of patients for whom the MSU was dispatched did not ultimately receive MSU care. We estimated the causal effect of additional MSU care on 3-month functional outcomes among B_PROUD patients for whom an MSU was dispatched. METHODS: We used data from the B_PROUD study (1 February 2017-8 May 2019). Given the presence of exposure-outcome unmeasured confounding, we used the front-door formula to identify the distribution of modified Rankin scale (mRS) outcomes under two hypothetical interventions: (1) receiving additional MSU care and (2) only receiving conventional care. We considered the time from dispatch to thrombolysis as the full mediator and adjusted for exposure-mediator and mediator-outcome confounding. We used a parametric estimator to estimate the common odds ratio (cOR) and 95% bootstrapped confidence intervals (CI). RESULTS: We included in total 768 ischemic stroke/TIA patients with MSU dispatch. The MSU was canceled for 180 (23%) patients, whereas 588 (77%) received MSU care. The unadjusted association between the care group and mRS favored conventional care (cOR = 1.7; 95% CI = 1.2, 2.3); however, after applying the front-door formula, the mRS distribution favored MSU care (cOR = 0.88; 95% CI = 0.81, 0.96). CONCLUSIONS: Receiving MSU care was associated with better functional outcomes than conventional care only, compatible with the hypothesized beneficial effect of MSU care on poststroke outcomes, among stroke and TIA patients without contraindications to reperfusion treatments.

Association of cerebrospinal fluid brain-binding autoantibodies with cognitive impairment in post-COVID-19 syndrome.

BACKGROUND: Neurological symptoms, in particular cognitive deficits, are common in post-COVID-19 syndrome (PCS). There is no approved therapy available, and the underlying disease mechanisms are largely unknown. Besides others, autoimmune processes may play a key role. DESIGN: We here present data of a prospective study conducted between September 2020 and December 2021 and performed at two German University hospitals with specialized Neurology outpatient clinics. Fifty patients with self-reported cognitive deficits as main complaint of PCS and available serum and CSF samples were included. Cell-based assays and indirect immunofluorescence on murine brain sections were used to detect autoantibodies against intracellular and surface antigens in serum and CSF and analyzed for associations with cognitive screening assessment. RESULTS: Clearly abnormal cognitive status (MoCA ≤ 25/30 points) was only seen in 18/50 patients with self-reported cognitive deficits. Most patients (46/50) had normal routine CSF parameters. anti-neuronal autoantibodies were found in 52 % of all patients: n = 9 in serum only, n = 3 in CSF only and n = 14 in both, including those against myelin, Yo, Ma2/Ta, GAD65 and NMDA receptor, but also a variety of undetermined epitopes on brain sections. These included cerebral vessel endothelium, Purkinje neurons, granule cells, axon initial segments, astrocytic proteins and neuropil of basal ganglia or hippocampus as well as a formerly unknown perinuclear rim pattern. Pathological MoCA results were associated with the presence of anti-neuronal antibodies in CSF (p = 0.0004). CONCLUSIONS: Autoantibodies targeting brain epitopes are common in PCS patients and strongly associate with pathological cognitive screening tests, in particular when found in CSF. Several underlying autoantigens still await experimental identification. Further research is needed to inform on the clinical relevance of these autoantibodies, including controlled studies that explore the potential efficacy of antibody-depleting immunotherapy in PCS.

Mobile Stroke Units: Evidence, Gaps, and Next Steps.

Mobile stroke units (MSUs) are specialized ambulances equipped with the personnel, equipment, and imaging capability to diagnose and treat acute stroke in the prehospital setting. Over the past decade, MSUs have proliferated throughout the world, particularly in European and US cities, culminating in the formation of an international consortium. Randomized trials have demonstrated that MSUs increase stroke thrombolysis rates and reduce onset-to-treatment times but until recently it was uncertain if these advantages would translate into better patient outcomes. In 2021, 2 pivotal, large, controlled clinical trials, B_PROUD and BEST-MSU, demonstrated that as compared with conventional emergency care, treatment aboard MSUs was safe and led to improved functional outcomes in patients with stroke. Further, the observed benefit of MSUs appeared to be primarily driven by the higher frequency of ultra-early thrombolysis within the golden hour. Nevertheless, questions remain regarding the cost-effectiveness of MSUs, their utility in nonurban settings, and optimal infrastructure. In addition, in much of the world, MSUs are currently not reimbursed by insurers nor accepted as standard care by regulatory bodies. As MSUs are now established as one of the few proven acute stroke interventions with an effect size that is comparable to that of intravenous thrombolysis and stroke units, stroke leaders and organizations should work with emergency medical services, governments, and community stakeholders to determine how MSUs might benefit individual communities, and their optimal organization and financing. Future research to explore the effect of MSUs on intracranial hemorrhage and thrombectomy outcomes, cost-effectiveness, and novel models including the use of rendezvous transports, helicopters, and advanced neuroimaging is ongoing. Recommended next steps for MSUs include reimbursement by insurers, integration with ambulance networks, recognition by program accreditors, and inclusion in registries that monitor care quality.

Patient-Centered Outcomes in a Randomized Trial Investigating a Multimodal Prevention Program After Transient Ischemic Attack or Minor Stroke: The INSPiRE-TMS Trial.

BACKGROUND: The INSPiRE-TMS trial (Intensified Secondary Prevention Intending a Reduction of Recurrent Events in Transient Ischemic Attack and Minor Stroke Patients) investigated effects of a multicomponent support program in patients with nondisabling stroke or transient ischemic attack. Although secondary prevention targets were achieved more frequently in the intensified care group, no significant differences were seen in rates of recurrent major vascular events. Here, we present the effects on prespecified patient-centered outcomes. METHODS: In a multicenter trial, we randomized patients with modifiable risk factors either to the intensified or conventional care alone program. Intensified care was provided by stroke specialists and used feedback and motivational interviewing strategies (≥8 outpatient visits over 2 years) aiming to improve adherence to secondary prevention targets. We measured physical fitness, disability, cognitive function and health-related quality of life by stair-climbing test, modified Rankin Scale, Montreal Cognitive Assessment, and European Quality of Life 5 Dimension 3 Level during the first 3 years of follow-up. RESULTS: Of 2072 patients (mean age: 67.4years, 34% female) assessed for the primary outcome, patient-centered outcomes were collected in 1,771 patients (877 intensified versus 894 conventional care group). Physical fitness improved more in the intensified care group (mean between-group difference in power (Watt): 24.5 after 1 year (95% CI, 5.5-43.5); 36.1 after 2 years (95% CI, 13.1-59.7) and 29.6 (95% CI, 2.0-57.3 after 3 years). At 1 year, there was a significant shift in ordinal regression analysis of modified Rankin Scale in favor of the intensified care group (common odds ratio, 1.23 [95% CI, 1.03-1.47]) but not after 2 (odds ratio, 1.17 [95% CI, 0.96-1.41]) or 3 years (odds ratio, 1.16 [95% CI, 0.95-1.43]) of follow-up. However, Montreal Cognitive Assessment and European Quality of Life 5 Dimension scores showed no improvement in the intensified intervention arm after 1, 2, or 3 years of follow-up. CONCLUSIONS: Patients of the intensified care program group had slightly better results for physical fitness and modified Rankin Scale after 1 year, but none of the other patient-centered outcomes was significantly improved. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01586702.

Shifting acute stroke management to the prehospital setting.

PURPOSE OF REVIEW: The earlier the treatment, the better the outcomes after acute ischemic stroke. Optimizing prehospital care bears potential to shorten treatment times. We here review the recent literature on mothership vs. drip-and-ship as well as mobile stroke unit concepts. RECENT FINDINGS: Mobile stroke units result in the shortest onset-to-treatment times in mostly urban settings. SUMMARY: Future research should focus on further streamlining processes around mobile stroke units, especially improving dispatch algorithms and improve referral for endovascular therapy.

Cardiac Troponin and Recurrent Major Vascular Events after Minor Stroke or Transient Ischemic Attack.

OBJECTIVE: This study was undertaken to investigate whether high-sensitivity cardiac troponin T (hs-cTnT) is associated with major adverse cardiovascular events (MACE) in patients with minor stroke or transient ischemic attack (TIA), and whether this association differs after risk stratification based on the Age, Blood Pressure, Clinical Features, Duration of Symptoms, Diabetes (ABCD2 ) score. METHODS: INSPiRE-TMS was a randomized controlled trial allocating patients with minor stroke or TIA to an intensified support program or conventional care. In this post hoc analysis, participants were categorized using hs-cTnT levels (5th generation; Roche Diagnostics, Manheim, Germany; 99th percentile upper reference limit [URL] = 14ng/l). Vascular risk was stratified using the ABCD2 score (lower risk = 0-5 vs higher risk = 6-7). Cox proportional hazard regression was performed using covariate adjustment and propensity score matching (PSM) for the association between hs-cTnT and MACE (stroke/nonfatal coronary event/vascular death). RESULTS: Among 889 patients (mean age = 70 years, 37% female), MACE occurred in 153 patients (17.2%) during a mean follow-up of 3.2 years. hs-cTnT was associated with MACE (9.3%/yr, >URL vs 4.4%/yr, ≤URL, adjusted hazard ratio [HR] = 1.63 [95% confidence interval (CI) = 1.13-2.35], adjusted HR [Q4 vs Q1 ] = 2.57 [95% CI = 1.35-4.97], adjusted HR [log-transformed] = 2.31 [95% CI = 1.37-3.89]). This association remained after PSM (adjusted HR = 1.76 [95% CI = 1.14-2.72]). There was a significant interaction between hs-cTnT and ABCD2 category for MACE occurrence (pinteraction  = 0.04). In the lower risk category, MACE rate was 9.5%/yr in patients with hs-cTnT > URL, which was higher than in those ≤URL (3.8%/yr) and similar to the overall rate in the higher risk category. INTERPRETATION: hs-cTnT levels are associated with incident MACE within 3 years after minor stroke or TIA and may help to identify high-risk individuals otherwise deemed at lower risk based on the ABCD2 score. If confirmed in independent validation studies, this might warrant intensified secondary prevention measures and cardiac diagnostics in stroke patients with elevated hs-cTnT. ANN NEUROL 2021;90:901-912.

Association Between Use of a Flying Intervention Team vs Patient Interhospital Transfer and Time to Endovascular Thrombectomy Among Patients With Acute Ischemic Stroke in Nonurban Germany.

Importance: The benefit of endovascular thrombectomy (EVT) for acute ischemic stroke is highly time-dependent, and it is challenging to expedite treatment for patients in remote areas. Objective: To determine whether deployment of a flying intervention team, compared with patient interhospital transfer, is associated with a shorter time to endovascular thrombectomy and improved clinical outcomes for patients with acute ischemic stroke. Design, Setting, and Participants: This was a nonrandomized controlled intervention study comparing 2 systems of care in alternating weeks. The study was conducted in a nonurban region in Germany including 13 primary telemedicine-assisted stroke centers within a telestroke network. A total of 157 patients with acute ischemic stroke for whom decision to pursue thrombectomy had been made and deployment of flying intervention team or patient interhospital transfer was initiated were enrolled between February 1, 2018, and October 24, 2019. The date of final follow-up was January 31, 2020. Exposures: Deployment of a flying intervention team for EVT in a primary stroke center vs patient interhospital transfer for EVT to a referral center. Main Outcomes and Measures: The primary outcome was time delay from decision to pursue thrombectomy to start of the procedure in minutes. Secondary outcomes included functional outcome after 3 months, determined by the distribution of the modified Rankin Scale score (a disability score ranging from 0 [no deficit] to 6 [death]). Results: Among the 157 patients included (median [IQR] age, 75 [66-80] y; 80 [51%] women), 72 received flying team care and 85 were transferred. EVT was performed in 60 patients (83%) in the flying team group vs 57 (67%) in the transfer group. Median (IQR) time from decision to pursue EVT to start of the procedure was 58 (51-71) minutes in the flying team group and 148 (124-177) minutes in the transfer group (difference, 90 minutes [95% CI, 75-103]; P < .001). There was no significant difference in modified Rankin Scale score after 3 months between patients in the flying team (n = 59) and transfer (n = 57) groups who received EVT (median [IQR] score, 3 [2-6] vs 3 [2-5]; adjusted common odds ratio for less disability, 1.91 [95% CI, 0.96-3.88]; P = .07). Conclusions and Relevance: In a nonurban stroke network in Germany, deployment of a flying intervention team to local stroke centers, compared with patient interhospital transfer to referral centers, was significantly associated with shorter time to EVT for patients with acute ischemic stroke. The findings may support consideration of a flying intervention team for some stroke systems of care, although further research is needed to confirm long-term clinical outcomes and to understand applicability to other geographic settings.

Stroke systems of care in high-income countries: what is optimal?

Stroke is a complex, time-sensitive, medical emergency that requires well functioning systems of care to optimise treatment and improve patient outcomes. Education and training campaigns are needed to improve both the recognition of stroke among the general public and the response of emergency medical services. Specialised stroke ambulances (mobile stroke units) have been piloted in many cities to speed up the diagnosis, triage, and emergency treatment of people with acute stroke symptoms. Hospital-based interdisciplinary stroke units remain the central feature of a modern stroke service. Many have now developed a role in the very early phase (hyperacute units) plus outreach for patients who return home (early supported discharge services). Different levels (comprehensive and primary) of stroke centre and telemedicine networks have been developed to coordinate the various service components with specialist investigations and interventions including rehabilitation. Major challenges include the harmonisation of resources for stroke across the whole patient journey (including the rapid, accurate triage of patients who require highly specialised treatment in comprehensive stroke centres) and the development of technology to improve communication across different parts of a service.

High frequency of cerebrospinal fluid autoantibodies in COVID-19 patients with neurological symptoms.

BACKGROUND: COVID-19 intensive care patients can present with neurological syndromes, usually in the absence of SARS-CoV-2 in cerebrospinal fluid (CSF). The recent finding of some virus-neutralizing antibodies cross-reacting with brain tissue suggests the possible involvement of specific autoimmunity. DESIGN: Blood and CSF samples from eleven critically ill COVID-19 patients presenting with unexplained neurological symptoms including myoclonus, oculomotor disturbance, delirium, dystonia and epileptic seizures, were analyzed for anti-neuronal and anti-glial autoantibodies. RESULTS: Using cell-based assays and indirect immunofluorescence on unfixed murine brain sections, all patients showed anti-neuronal autoantibodies in serum or CSF. Antigens included intracellular and neuronal surface proteins, such as Yo or NMDA receptor, but also various specific undetermined epitopes, reminiscent of the brain tissue binding observed with certain human monoclonal SARS-CoV-2 antibodies. These included vessel endothelium, astrocytic proteins and neuropil of basal ganglia, hippocampus or olfactory bulb. CONCLUSION: The high frequency of autoantibodies targeting the brain in the absence of other explanations suggests a causal relationship to clinical symptoms, in particular to hyperexcitability (myoclonus, seizures). Several underlying autoantigens and their potential molecular mimicry with SARS-CoV-2 still await identification. However, autoantibodies may already now explain some aspects of multi-organ disease in COVID-19 and can guide immunotherapy in selected cases.

The "Flying Intervention Team": A Novel Stroke Care Concept for Rural Areas.

BACKGROUND: Endovascular treatment of large vessel occlusion in acute ischemic stroke patients is difficult to establish in remote areas, and time dependency of treatment effect increases the urge to develop health care concepts for this population. SUMMARY: Current strategies include direct transportation of patients to a comprehensive stroke center (CSC) ("mothership model") or transportation to the nearest primary stroke center (PSC) and secondary transfer to the CSC ("drip-and-ship model"). Both have disadvantages. We propose the model "flying intervention team." Patients will be transported to the nearest PSC; if telemedically identified as eligible for thrombectomy, an intervention team will be acutely transported via helicopter to the PSC and endovascular treatment will be performed on site. Patients stay at the PSC for further stroke unit care. This model was implemented at a telestroke network in Germany. Fifteen remote hospitals participated in the project, covering 14,000 km2 and a population of 2 million. All have well established telemedically supported stroke units, an angiography suite, and a helicopter pad. Processes were defined individually for each hospital and training sessions were implemented for all stroke teams. An exclusive project helicopter was installed to be available from 8 a.m. to 10 p.m. during 26 weeks per year. Key Messages: The model of the flying intervention team is likely to reduce time delays since processes will be performed in parallel, rather than consecutively, and since it is quicker to move a medical team rather than a patient. This project is currently under evaluation (clinicaltrials NCT04270513).

Association Between Dispatch of Mobile Stroke Units and Functional Outcomes Among Patients With Acute Ischemic Stroke in Berlin.

Importance: Effects of thrombolysis in acute ischemic stroke are time-dependent. Ambulances that can administer thrombolysis (mobile stroke units [MSUs]) before arriving at the hospital have been shown to reduce time to treatment. Objective: To determine whether dispatch of MSUs is associated with better clinical outcomes for patients with acute ischemic stroke. Design, Setting, and Participants: This prospective, nonrandomized, controlled intervention study was conducted in Berlin, Germany, from February 1, 2017, to October 30, 2019. If an emergency call prompted suspicion of stroke, both a conventional ambulance and an MSU, when available, were dispatched. Functional outcomes of patients with final diagnosis of acute cerebral ischemia who were eligible for thrombolysis or thrombectomy were compared based on the initial dispatch (both MSU and conventional ambulance or conventional ambulance only). Exposure: Simultaneous dispatch of an MSU (computed tomographic scanning with or without angiography, point-of-care laboratory testing, and thrombolysis capabilities on board) and a conventional ambulance (n = 749) vs conventional ambulance alone (n = 794). Main Outcomes and Measures: The primary outcome was the distribution of modified Rankin Scale (mRS) scores (a disability score ranging from 0, no neurological deficits, to 6, death) at 3 months. The coprimary outcome was a 3-tier disability scale at 3 months (none to moderate disability; severe disability; death) with tier assignment based on mRS scores if available or place of residence if mRS scores were not available. Common odds ratios (ORs) were used to quantify the association between exposure and outcome; values less than 1.00 indicated a favorable shift in the mRS distribution and lower odds of higher levels of disability. Results: Of the 1543 patients (mean age, 74 years; 723 women [47%]) included in the adjusted primary analysis, 1337 (87%) had available mRS scores (primary outcome) and 1506 patients (98%) had available the 3-tier disability scale assessment (coprimary outcome). Patients with an MSU dispatched had lower median mRS scores at month 3 (1; interquartile range [IQR], 0-3) than did patients without an MSU dispatched (2; IQR, 0-3; common OR for worse mRS, 0.71; 95% CI, 0.58-0.86; P < .001). Similarly, patients with an MSU dispatched had lower 3-month coprimary disability scores: 586 patients (80.3%) had none to moderate disability; 92 (12.6%) had severe disability; and 52 (7.1%) had died vs patients without an MSU dispatched: 605 (78.0%) had none to moderate disability; 103 (13.3%) had severe disability; and 68 (8.8%) had died (common OR for worse functional outcome, 0.73, 95% CI, 0.54-0.99; P = .04). Conclusions and Relevance: In this prospective, nonrandomized, controlled intervention study of patients with acute ischemic stroke in Berlin, Germany, the dispatch of mobile stroke units, compared with conventional ambulances alone, was significantly associated with lower global disability at 3 months. Clinical trials in other regions are warranted.

The role of cardiologists on the stroke unit.

Cardiologists need a better understanding of stroke and of cardiac implications in modern stroke management. Stroke is a leading disease in terms of mortality and disability in our society. Up to half of ischaemic strokes are directly related to cardiac and large artery diseases and cardiovascular risk factors are involved in most other strokes. Moreover, in an acute stroke direct central brain signals and a consecutive autonomic/vegetative imbalance may account for severe and life-threatening cardiovascular complications. The strong cerebro-cardiac link in acute stroke has recently been addressed as the stroke-heart syndrome that requires careful cardiovascular monitoring and immediate therapeutic measures. The regular involvement of cardiologic expertise in daily work on a stroke unit is therefore of high importance and a cornerstone of up-to-date comprehensive stroke care concepts. The main targets of the cardiologists' contribution to acute stroke care can be categorized in three main areas (i) diagnostics workup of stroke aetiology, (ii) treatment and prevention of complications, and (iii) secondary prevention and sub-acute workup of cardiovascular comorbidity. All three aspects are by themselves highly relevant to support optimal acute management and to improve the short-term and long-term outcomes of patients. In this article, an overview is provided on these main targets of cardiologists' contribution to acute stroke management.

Clinical significance of acute and chronic ischaemic lesions in multiple cerebral vascular territories.

OBJECTIVES: To investigate the association between acute and chronic ischaemic lesions in a multiple territory lesion pattern (MTLP) detected by 3-Tesla MRI and stroke aetiology, specifically atrial fibrillation-associated stroke. METHODS: We analysed data from the 1000+ study - a prospective, observational 3-Tesla MRI cohort study of consecutively included acute stroke patients. Acute and chronic lesions were detected by DWI and fluid-attenuated inversion recovery, respectively. Observers blinded to clinical data allocated lesions to the right anterior, left anterior or posterior circulation. Lesion pattern was categorised as MTLPa/c when more than one territory was affected by either acute or chronic lesions or as MTLPa when more than one territory was affected by acute lesions alone. RESULTS: Of the 1,000 included patients, an MTLPa/c was found in 43% and MTLPa in 24%. Advanced age (aOR=1.21 per 10 years, 95% CI 1.06-1.39), atrial fibrillation (aOR=1.44, 95% CI 1.06-1.94), aortic arch atherosclerosis (aOR=2.52, 95% CI 1.10-5.77), malignant disease (aOR=1.99, 95% CI 1.25-3.16) and lower estimated glomerular filtration rate (eGFR) (aOR=0.90 per 10 ml, 95% CI 0.84-0.97) were associated with MTLPa/c. Only malignant disease (aOR=2.03, 95% CI 1.27-3.23) and lower eGFR (aOR=0.91 per 10 ml, 95% CI 0.85-0.97) were associated with MTLPa. CONCLUSIONS: An MRI-detected multiple territory lesion pattern of acute and chronic ischaemic lesions is frequent and more often present in older patients and patients with atrial fibrillation, aortic arch atherosclerosis, malignant disease and lower eGFR. Considering not only acute but also chronic ischaemic lesions may facilitate identifying atrial fibrillation-associated or aorto-embolic stroke. KEY POINTS: • Brain imaging with MRI may help to determine the aetiology of stroke. • Of 1,000 stroke patients undergoing 3-Tesla MRI, 43% had acute and chronic ischaemic lesions in multiple cerebral vascular territories. • Atrial fibrillation, aortic arch atherosclerosis and malignant disease were associated with a multiple territory lesion pattern.

Ultraearly Intravenous Thrombolysis for Acute Ischemic Stroke in Mobile Stroke Unit and Hospital Settings.

Background and Purpose- Mobile stroke units (MSUs) are known to increase the proportion of acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT) in the first golden hour (GH) after onset compared with hospital settings (HS). However, because of the low number of AIS patients treated with intravenous thrombolysis within this ultraearly time window in conventional care, characteristics, and outcome of this subgroup of AIS patients have not been compared between MSU and HS. Methods- MSU-GH patients were selected from the Berlin-based MSU (STEMO [Stroke Emergency Mobile]), whereas HS-GH patients were selected from the SITS-EAST (Safe Implementation of Treatments in Stroke-East) registry. The outcome events of interest included the rates of favorable functional outcome (modified Rankin Scale scores of 0 or 1), distribution of the modified Rankin Scale scores, and mortality after 3 months between MSU-GH and HS-GH groups. Results- We identified 117 MSU-GH (38.4% of 305 MSU-treated patients) and 136 HS-GH (0.9% of 15 591 HS-treated patients) eligible patients without prestroke disability. No significant differences were documented in the rates of favorable functional outcome (51.3% versus 46.2%, P=0.487) and mortality (7.7% versus 9.9%, P=0.576) at 3 months, or in the distribution of 3-month modified Rankin Scale scores between the 2 groups ( P=0.196). In multivariable logistic regression analyses, adjusting for potential confounders, MSU treatment was not associated with a significantly different likelihood of favorable functional outcome (odds ratio, 1.84 for MSU patients; 95% CI, 0.86-3.96) or mortality (odds ratio, 0.95; 95% CI, 0.28-3.20) at 3 months. Conclusions- There is no evidence that safety and efficacy of ultraearly intravenous thrombolysis for AIS differs when used in MSUs or in HS.