Search

Introduction: Endovascular treatment (EVT) is a therapeutic option for cerebral venous thrombosis (CVT); however, its benefit over conservative medical management has not been proven. Whether the current patient selection practices are appropriate for EVT is unclear. Methods: This was a nationwide study of the 2016–2020 National Inpatient Sample database. Adult CVT patients and EVT treatments were identified. Patient demographics, medical comorbidities, CVT risk factors, and CVT manifestations were identified. Presence of radiographic signs of advanced and severe CVT (venous infarction, cerebral edema, and intracranial hemorrhage) was recorded. Primary and secondary outcomes were good discharge outcomes and in-hospital mortality, respectively. Results: A total of 17,130 CVT patients were identified, and 56.7% had good discharge outcomes, while 4.6% died during hospitalization. 945 (5.5%) received EVT, and EVT patients were more likely to have cerebral infarction (35.4 vs. 21.8%, p < 0.001), edema (35.4 vs. 20.1%, p < 0.001), and hemorrhage (37.6 vs. 19.7%, p < 0.001). After multivariable adjustments, EVT for patients without infarction, edema, or hemorrhage was moderately associated with higher odds of good outcomes (OR 1.86 [95% CI 0.98–3.53], p = 0.059) and resulted in zero deaths. However, with the increasing burden of radiographic signs of advanced CVT measured by the cumulative presence of infarction, edema, and hemorrhage, EVT was associated with decreasing odds of good outcomes and increasing odds of in-hospital mortality compared to medical management (interaction p = 0.046 and 0.029, respectively). Conclusions: EVT may lead to higher rates of favorable hospitalization outcomes in patients who have not yet developed overt parenchymal manifestations of backpressure changes; presence of infarction, edema, and hemorrhage may diminish the short-term effectiveness of EVT. [ABSTRACT FROM AUTHOR]

Introduction: Careful monitoring of patients who receive intravenous thrombolysis (IVT) for acute ischemic stroke (AIS) is resource-intensive, and potentially less relevant in those with mild degrees of neurological impairment who are at low risk of symptomatic intracerebral hemorrhage (sICH) and other complications. Methods: OPTIMISTmain is an international, multicenter, prospective, stepped wedge, cluster randomized, blinded outcome assessed trial aims to determine whether a less-intensity monitoring protocol is at least as effective, safe, and efficient as standard post-IVT monitoring in patients with mild deficits post-AIS. Clinically stable adult patients with mild AIS (defined by a NIHSS <10) who do not require intensive care within 2 h post-IVT are recruited at hospitals in Australia, Chile, China, Malaysia, Mexico, UK, USA, and Vietnam. An average of 15 patients recruited per period (overall 60 patient participants) at 120 sites for a total of 7,200 IVT-treated AIS patients will provide 90% power (one-sided α 0.025). The initiation of eligible hospitals is based on a rolling process whenever ready, stratified by country. Hospitals are randomly allocated using permuted blocks into 3 sequences of implementation, stratified by country and the projected number of patients to be recruited over 12 months. These sequences have four periods that dictate the order in which they are to switch from control (usual care) to intervention (implementation of low intensity monitoring protocol) to different clusters of patients in a stepped manner. Compared to standard monitoring, the low-intensity monitoring protocol includes assessments of neurological and vital signs every 15 min for 2 h, 2 hourly (vs. every 30 min) for 8 h, and 4 hourly (vs. every 1 h) until 24 h, post-IVT. The primary outcome measure is functional recovery, defined by the modified Rankin scale (mRS) at 90 days, a seven-point ordinal scale (0 [no residual symptom] to 6 [death]). Secondary outcomes include death or dependency, length of hospital stay, and health-related quality of life, sICH, and serious adverse events. Conclusion: OPTIMISTmain will provide level I evidence for the safety and effectiveness of a low-intensity post-IVT monitoring protocol in patients with mild severity of AIS. [ABSTRACT FROM AUTHOR]

Introduction: The treatment of acute ischemic stroke due to large artery vessel occlusion experienced a dramatic development within the last decade. This meta-analysis investigates the effectiveness of bridging therapy (BT) versus mechanical thrombectomy (MT) alone in treating acute ischemic stroke. Methods: Two independent reviewers assessed two-arm clinical trials from Scopus, PubMed, Web of Science, and the Cochrane Library up to January 2024. Data extraction and quality were evaluated using the ROBINS-2 tool. Our primary outcomes were improvement in NIHSS scores and 90-day modified Rankin Scale (mRS) score. Results: This meta-analysis, which included 2,638 participants from 8 randomized controlled trials, found that BT resulted in a greater improvement in NIHSS scores from baseline compared to endovascular treatment alone (mean difference [MD] 0.96, 95% confidence interval [CI]: [0.73–1.20], p < 0.00001). Additionally, BT group achieved successful recanalization more frequently before and after thrombectomy. Thrombectomy alone hat a shorter time from stroke onset to groin puncture compared to BT (MD 9.91, 95% CI: [4.31–15.52], p = 0.005). Functional outcomes, mortality rates, symptomatic intracerebral hemorrhage rates, and long-term recovery metrics, such as Barthel index and modified Rankin Scale scores, were comparable between both treatment approaches. Conclusion: BT is superior to endovascular treatment alone based on NIHSS score improvement and successful reperfusion rates before and after thrombectomy. Despite MT alone demonstrating a shorter time from stroke onset to groin puncture (MD of 9.91 min), it did not contribute to greater NIHSS improvement at 24 h and 7 days. Further trials with larger sample sizes are warranted to enhance precision in clinical guidance. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to determine predictors of early (END) and delayed neurological deterioration (DND) and their association with the functional outcome in patients with acute ischemic stroke (AIS) who participated in the international Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Methods: END and DND (without END) were defined as scores of a ≥2-point increase on the National Institutes of Health Stroke Scale (NIHSS) or a ≥1-point decrease on the Glasgow coma scale or death, from baseline to 24 h and 24–72 h, respectively. Multivariable logistic regression models were used to determine independent predictors of END and DND and their association with 90-day outcomes (dichotomous scores on the modified Rankin scale [mRS] of 2–6 vs. 0–1 and 3–6 vs. 0–2 and death). Results: Of 4,496 patients, 871 (19.4%) and 302 (8.4%) patients experienced END and DND, respectively. Higher baseline NIHSS score, older age, large-artery occlusion due to significant atheroma, cardioembolic stroke subtype, hemorrhagic infarction and parenchymatous hematoma within 24 h were all independent predictors for both END (all p ≤ 0.01) and DND (all p ≤ 0.024). Moreover, higher baseline systolic blood pressure (BP) (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.02–1.12), higher diastolic BP variability within 24 h (OR 1.07, 95% CI 1.04–1.09), patients from Asia (OR 1.25, 95% CI 1.03–1.52) were the only independent predictors for END. However, Asian ethnicity was negatively associated with DND (OR 0.64, 95% CI 0.47–0.86). Hemorrhagic infarction and parenchymatous hematoma within 24 h were the key predictors of END across all stroke subtypes. END and DND were all associated with a poor functional outcome at 90 days (all p < 0.001). Conclusion: We identified overlapping and unique demographic and clinical predictors of END and DND after thrombolysis for AIS. Both END and DND predict unfavorable outcomes at 90 days. [ABSTRACT FROM AUTHOR]

Introduction: The ongoing OPTIMISTmain study, an international, multicenter, stepped-wedge cluster randomized trial, aims to determine effectiveness and safety of low-intensity versus standard monitoring in thrombolysis-treated patients with mild-to-moderate acute ischemic stroke (AIS). An embedded process evaluation explored integration and impact of the intervention on care processes at participating US sites. Methods: A mixed-methods approach with quantitative and qualitative data was collected between September 2021 and November 2022. Implementer surveys were undertaken at pre- and post-intervention phases to understand the perceptions of low-intensity monitoring strategy. A sample of stroke care nurses were invited to participate in semi-structured interviews at an early stage of post-intervention. Qualitative data were analyzed deductively using the normalization process theory; quantitative data were tabulated. Results: Interviews with 21 nurses at 8 hospitals have shown low-intensity monitoring was well accepted as there were less time constraints and reduced workload for each patient. There were initial safety concerns over missing deteriorating patients and difficulties in changing established routines. Proper training, education, and communication, and changing the habits and culture of care, were key elements to successfully adopting the new monitoring care into routine practice. Similar results were found in the post-intervention survey (42 nurses from 13 hospitals). Nurses reported time being freed up to provide patient education (56%), daily living care (50%), early mobilization (26%), mood/cognition assessment (44%), and other aspects (i.e., communication, family support). Conclusions: Low-intensity monitoring for patients with mild-to-moderate AIS, facilitated by appropriate education and organizational support, appears feasible and acceptable at US hospitals. [ABSTRACT FROM AUTHOR]

Introduction: The aim of the study was to investigate the impact of time interval between start of intravenous thrombolysis (IVT) to start of endovascular thrombectomy (EVT) on stroke outcomes. Methods: Data from the Quality Improvement and Clinical Research (QuICR) provincial stroke registry from Alberta, Canada, were used to identify stroke patients who received IVT and EVT from January 2015 to December 2019. We assessed the impact of the time interval between IVT bolus to EVT puncture (needle-to-puncture times [NPT]) on outcomes. Radiological outcomes included successful initial recanalization (revised Arterial Occlusive Lesion 2b–3), successful initial and final reperfusion (modified thrombolysis in cerebral infarction 2b–3). Clinical outcomes were 90-day modified Rankin Scale (mRS) and mortality. Results: Of the 680 patients, 233 patients (median age: 73, 41% females) received IVT + EVT. Median NPT was 38 min (IQR, 24–60). Arrival during working hours was independently associated with shorter NPT (p < 0.001). Successful initial recanalization and initial and final reperfusion were observed in 12%, 10%, and 83% of patients, respectively. NPT was not associated with initial successful recanalization (OR 0.97 for every 10-min increase of NPT, 95% CI: 0.91–1.04), initial successful reperfusion (OR 1.01, 95% CI: 0.96–1.07), or final successful reperfusion (OR: 1.03, 95% CI: 0.97–1.08). Every 10-min delay in NPT was associated with lower odds of functional independence at 90 days (mRS ≤2; OR: 0.93; 95% CI, 0.88–0.97). Patients with shorter NPT (≤38 min) had lower 90-day mRS scores (median 1 vs. 3; OR: 0.54 [0.31–0.91]) and had lower mortality (6.1% vs. 21.2%; OR, 0.23 [0.10–0.57]) than the longer NPT group. Conclusion: Shorter NPT did not impact reperfusion outcomes but was associated with better clinical outcome. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to determine the safety and efficacy of intravenous (IV) alteplase at 0.6 mg/kg for patients with acute wake-up or unclear-onset strokes in clinical practice. Methods: This multicenter observational study enrolled acute ischemic stroke patients with last-known-well time >4.5 h who had mismatch between DWI and FLAIR and were treated with IV alteplase. The safety outcomes were symptomatic intracranial hemorrhage (sICH) after thrombolysis, all-cause deaths, and all adverse events. The efficacy outcomes were favorable outcome defined as an mRS score of 0–1 or recovery to the same mRS score as the premorbid score, complete independence defined as an mRS score of 0–1 at 90 days, and change in NIHSS at 24 h from baseline. Results: Sixty-six patients (35 females; mean age, 74 ± 11 years; premorbid complete independence, 54 [82%]; median NIHSS on admission, 11) were enrolled at 15 hospitals. Two patients (3%) had sICH. Median NIHSS changed from 11 (IQR, 6.75–16.25) at baseline to 5 (3–12.25) at 24 h after alteplase initiation (change, −4.8 ± 8.1). At discharge, 31 patients (47%) had favorable outcome and 29 (44%) had complete independence. None died within 90 days. Twenty-three (35%) also underwent mechanical thrombectomy (no sICH, NIHSS change of −8.5 ± 7.3), of whom 11 (48%) were completely independent at discharge. Conclusions: In real-world clinical practice, IV alteplase for unclear-onset stroke patients with DWI-FLAIR mismatch provided safe and efficacious outcomes comparable to those in previous trials. Additional mechanical thrombectomy was performed safely in them. [ABSTRACT FROM AUTHOR]

Introduction: The aims of this study were to evaluate the relationship of clinical and imaging baseline factors and treatment on the occurrence of early neurological improvement (ENI) in the WAKE-UP trial of MRI-guided intravenous thrombolysis in unknown onset stroke and to examine the association of ENI with long-term favorable outcome in patients treated with intravenous thrombolysis. Methods: We analyzed data from all patients with at least moderate stroke severity, reflected by an initial National Institutes of Health Stroke Scale (NIHSS) score ≥4 randomized in the WAKE-UP trial. ENI was defined as a decrease in NIHSS of ≥8 or a decline to zero or 1 at 24 h after initial presentation to the hospital. Favorable outcome was defined as a modified Rankin Scale score of 0–1 at 90 days. We performed group comparison and multivariable analysis of baseline factors associated with ENI and performed mediation analysis to evaluate the effect of ENI on the relationship between intravenous thrombolysis and favorable outcome. Results: ENI occurred in 93 out of 384 patients (24.2%) and was more likely to occur in patients who received treatment with alteplase (62.4% vs. 46.0%, p = 0.009), had smaller acute diffusion-weighted imaging lesion volume (5.51 mL vs. 10.9 mL, p ≤ 0.001), and less often large-vessel occlusion on initial MRI (7/93 [12.1%] versus 40/291 [29.9%], p = 0.014). In multivariable analysis, treatment with alteplase (OR 1.97, 95% confidence interval [CI] 0.954–1.100), lower baseline stroke volume (OR 0.965, 95% CI: 0.932–0.994), and shorter time from symptom recognition to treatment (OR 0.994, 95% CI: 0.989–0.999) were independently associated with ENI. Patients with ENI had higher rates of favorable outcome at 90-day follow-up (80.6% vs. 31.3%, p ≤ 0.001). The occurrence of ENI significantly mediated the association of treatment with a good outcome, with ENI at 24 h explaining 39.4% (12.9–96%) of the treatment effect. Conclusion: Intravenous alteplase increases the odds of ENI in patients with at least moderate stroke severity, especially when given early. In patients with large-vessel occlusion, ENI is rarely observed without thrombectomy. ENI represents a good surrogate early marker of treatment effect as more than a third of good outcome at 90 days is explained by ENI at 24 h. [ABSTRACT FROM AUTHOR]

When spontaneous cervical spinal epidural hematoma (SCEH) presents with hemiparesis, it can be misdiagnosed with ischemic stroke (IS), and the treatment of IS such as thrombolysis may deteriorate the symptoms of patients with SCEH, leading to worse sequelae or even death. We reported 3 SCEH patients who were initially suspected as IS in our center between Jun 2020 and April 2022 and analyzed their clinical characteristics together with 48 patients reported in the literature from Jan 1995 to April 2022. Two of the 3 SCEH patients had neck symptoms, while none of them presented cranial nerve symptoms. Cranial computed tomography (CT) scans were negative; however, abnormal signals in the cervical spinal canal were observed during cranial computed tomography angiography (CTA) and subsequent cervical CT confirmed the diagnosis of SCEH. All of them avoid mistreatment with recombinant tissue plasminogen activator (rt-PA). Subsequently, we analyzed the clinical characteristics of a total of 51 patients. Thirteen of them developed symptoms during activity. Neck pain was an important sign of SCEH because 35 patients had neck pain or neck discomfort. Sensory impairment was reported in a small proportion of patients (11/51), which varied a lot in the patients. Some special manifestations highly suggested spinal cord lesions and provided evidence for the early differential diagnosis of SCEH and stroke, but the incidence of which was quite low: ipsilateral Horner syndrome in 2 patients, Brown-Séquard syndrome in 2 cases, and Lhermitte's sign in 1 case. Only a minority (8/51) of the patients were correctly diagnosed at the emergency unit using cervical CT. Six patients were correctly diagnosed when performing CTA. A large portion of the cases (21/51) were first misdiagnosed as IS, but no responsible lesions were found on cranial magnetic resonance imaging (MRI), and subsequent cervical MRI confirmed the diagnosis. Sixteen patients were diagnosed with SCEH after the deterioration of symptoms. A total of 13 patients received rt-PA, and 10 of them had symptoms aggravation after thrombolysis. For patients with acute onset of hemiparesis but without cranial nerve symptoms, especially those accompanied by clinical features such as neck pain, ipsilateral Horner syndrome, Brown-Séquard syndrome, and Lhermitte's sign, SCEH should be highly suspected rather than stroke. Careful differential diagnosis should be performed with a comprehensive medical history and thorough physical examination. Cervical CT scan is a reasonable choice for quick differential diagnosis prior to administering potentially harmful therapy, especially rt-PA. [ABSTRACT FROM AUTHOR]

Introduction: Cerebral small vessel disease (SVD) burden includes increased risk of poor functional outcomes after acute ischemic stroke (AIS). We aimed to investigate the impact of cerebral SVD on 3-month functional outcomes in patients with AIS who received endovascular treatment (EVT) and to determine whether SVD is associated with futile reperfusion (FR). Methods: Using a multicenter stroke registry, we analyzed consecutive patients with AIS with either intracranial and/or extracranial anterior circulation large artery occlusion, who were treated with EVT and achieved successful reperfusion (thrombolysis in cerebral infarction grade 2b–3). The cerebral SVD burden was evaluated using baseline brain magnetic resonance imaging using a modified Fazekas score (mFS). The main outcome variable was FR, defined as poor functional outcomes (modified Rankin scale 3–6) at 3 months after stroke, despite successful recanalization. Secondary outcomes included stroke progression/recurrence and any hemorrhagic transformation. Results: Among 10,890 patients with AIS, 577 (5.3%) received EVT within 12  h of onset, including 354 who met study eligibility criteria. FR was observed in 191 patients (53.5%) and was positively associated with SVD burden. After adjustment for covariates including age, sex, stroke etiology, initial stroke severity, collateral status, Alberta stroke program early CT score, initial serum glucose, systemic blood pressure, and vascular risk factors, mFS grade 3 was significantly associated with FR (odds ratio: 3.93, 95% confidence interval: 1.602–9.619; p = 0.003). Conclusions: We demonstrated that cerebral SVD assessed with baseline brain MRI is associated with the futility of successful recanalization after EVT and any hemorrhagic transformation but not with early stroke progression or recurrence. Nevertheless, our findings do not justify withholding EVT in otherwise eligible patients with AIS based on the presence of severe SVD. [ABSTRACT FROM AUTHOR]

Background and Purpose: Telemedicine for stroke patients' care (telestroke [TS]) has grown notably in recent decades and may offer advantages during health crisis. Hospital admissions related to stroke have decreased globally during the COVID-19 pandemic, but scarce information is available regarding the effect of COVID-19 in TS. Using a population-based TS registry, we investigated the impact of the first year of the COVID-19 pandemic throughout our TS network in Santiago, Chile. Methods: Stroke codes evaluated after the onset of COVID-19 restrictions in Chile (defined as March 15, 2020) were compared with those evaluated in 2019. We analyzed differences between number of stroke codes, thrombolysis rate, stroke severity, and time from the stroke onset to hospital admission. Results: We observed that the number of stroke codes and the number of patients undergoing reperfusion therapy did not change significantly (p = 0.669 and 0.415, respectively). No differences were found with respect to the median time from the stroke onset to admission (p = 0.581) or in National Institutes of Health Stroke Scale (NIHSS) scores (p = 0.055). The decision-making-to-needle time was significantly shorter in the COVID-19 period (median 5 min [IQR 3–8], p < 0.016), but no significant changes were found at the other times. Conclusions: This study demonstrates the potential of adapting TS to extreme situations such as the COVID-19 pandemic, as well as the importance of establishing networks that facilitate patient access to quality treatments. [ABSTRACT FROM AUTHOR]

Background: Previous literature has identified a survival advantage in acute ischemic stroke (AIS) patients with elevated body mass indices (BMIs), a phenomenon termed the "obesity paradox." Objective: The aim of this study was to evaluate the independent association between obesity and clinical outcomes following AIS. Methods: Weighted discharge data from the National Inpatient Sample were queried to identify AIS patients from 2015 to 2018. Multivariable logistic regression and Cox proportional hazards modeling were performed to evaluate associations between obesity (BMI ≥ 30) and clinical endpoints following adjustment for acute stroke severity and comorbidity burden. Results: Among 1,687,805 AIS patients, 216,775 (12.8%) were obese. Compared to nonobese individuals, these patients were younger (64 vs. 72 mean years), had lower baseline NIHSS scores (6.9 vs. 7.9 mean score), and a higher comorbidity burden. Multivariable analysis demonstrated independent associations between obesity and lower likelihood of mortality (adjusted odds ratio [aOR] 0.76, 95% confidence interval [CI]: 0.71, 0.82, p < 0.001; hazard ratio 0.84, 95% CI: 0.73, 0.97, p = 0.015), intracranial hemorrhage (aOR 0.87, 95% CI: 0.82, 0.93, p < 0.001), and routine discharge to home (aOR 0.97, 95% CI: 0.95, 0.99; p = 0.015). Mortality rates between obese and nonobese patients were significantly lower across stroke severity thresholds, but this difference was attenuated among high severity (NIHSS > 20) strokes (21.6% vs. 23.2%, p = 0.358). Further stratification of the cohort into BMI categories demonstrated a "U-shaped" association with mortality (underweight aOR 1.58, 95% CI: 1.39, 1.79; p < 0.001, overweight aOR 0.64, 95% CI: 0.42, 0.99; p = 0.046, obese aOR 0.77, 95% CI: 0.71, 0.83; p < 0.001, severely obese aOR 1.18, 95% CI: 0.74, 1.87; p = 0.485). Sub-cohort assessment of thrombectomy-treated patients demonstrated an independent association of obesity (BMI 30–40) with lower mortality (aOR 0.79, 95% CI: 0.65, 0.96; p = 0.015), but not with routine discharge. Conclusion: This cross-sectional analysis demonstrates a lower likelihood of discharge to home as well as in-hospital mortality in obese patients following AIS, suggestive of a protective effect of obesity against mortality but not against all poststroke neurological deficits in the short term which would necessitate placement in acute rehabilitation and long-term care facilities. [ABSTRACT FROM AUTHOR]

Background: Presentation with mild symptoms is a common reason for intravenous thrombolysis (IVT) nonuse among acute ischemic stroke (AIS) patients. We examined the impact of IVT on the outcomes of mild AIS over time. Methods: Using the Paul Coverdell National Stroke Program data, we examined trends in IVT utilization from 2010 to 2019 among AIS patients presenting with National Institutes of Health Stroke Scale (NIHSS) scores ≤5. Outcomes adjudicated included rates of discharge to home and ability to ambulate independently at discharge. We used generalized estimating equation models to examine the effect of IVT on outcomes of AIS patients presenting with mild symptoms and calculated adjusted odds ratio (AOR) with 95% confidence intervals (CI). Results: During the study period, 346,762 patients presented with mild AIS symptoms. Approximately 6.2% were treated with IVT. IVT utilization trends increased from 3.7% in 2010 to 7.7% in 2019 (p < 0.001). Patients treated with IVT had higher median NIHSS scores upon presentation (IVT 3 [2, 4] vs. no IVT 2 [0, 3]). Rates of discharge to home (AOR 2.06, 95% CI: 1.99–2.13) and ability to ambulate at time of discharge (AOR 1.82, 95% CI: 1.76–1.89) were higher among those treated with IVT. Conclusion: There was an increased trend in IVT utilization among AIS patients presenting with mild symptoms. Utilization of IVT increased the odds of being discharged to home and the ability to ambulate at discharge independently in patients with mild stroke. [ABSTRACT FROM AUTHOR]

Background: It has been 50 years since the first explorations of the physiology of cerebral ischemia by measuring cerebral blood flow (CBF), and 25 years since the approval of tissue plasminogen activator for treating acute ischemic stroke. My personal career began and matured during those eras. Here, I provide my perspective on the evolution of acute stroke research and treatment from 1971 to the present, with some in-depth discussion of the National Institutes of Neurologic Disease and Stroke (NINDS) tissue-type plasminogen activator (tPA) stroke trial and development of mobile stroke units. Summary: Studies of CBF and metabolism in acute stroke patients revealed graded tissue injury that was dependent on the duration of ischemia. Subsequent animal research unraveled the biochemical cascade of events occurring at the cellular level after cerebral ischemia. After a decade of failed translation, the development of a relatively safe thrombolytic allowed us to achieve reperfusion and apply the lessons from earlier research to achieve positive clinical results. The successful conduct of the NINDS tPA stroke study coupled with positive outcomes from companion tPA studies around the world created the specialty of vascular neurology. This was followed by an avalanche of research in imaging, a focus on enhancing reperfusion through thrombectomy, and improving delivery of faster treatment culminating in mobile stroke units. Key Messages: The last half century has seen the birth and evolution of successful acute stroke treatment. More research is needed in developing new drugs and catheters to build on the advances we have already made with reperfusion and also in evolving our systems of care to get more patients treated more quickly in the prehospital setting. The history of stroke treatment over the last 50 years exemplifies that medical "science" is an evolving discipline worth an entire career's dedication. What was impossible 50 years ago is today's standard of care, what we claim as dogma today will be laughed at a decade from now, and what appears currently impossible will be tomorrow's realities. [ABSTRACT FROM AUTHOR]

Background and Purpose: As outcomes for acute ischemic stroke (AIS) vary according to clinical profile and management approaches, we aimed to determine disparities in clinical outcomes between Asian and non-Asian participants of the international, Enhanced Control of Hypertension and Thrombolysis Stroke study (ENCHANTED). Methods: ENCHANTED was a multicenter, prospective, partial-factorial, randomized, open trial of low-dose (0.6 mg/kg) versus standard-dose (0.9 mg/kg) alteplase, and intensive (target systolic blood pressure [SBP] 130–140 mm Hg) or guideline-recommended (<180 mm Hg) BP management, in thrombolysis-eligible AIS patients. Logistic regression models were used to examine the associations with outcomes of death or disability (modified Rankin scale [mRS] scores 2–6), major disability (mRS 3–5), death, and intracranial hemorrhage (ICH), with adjustment prognostic factors, alteplase dose, and mean SBP over 1–24 h. Results: Among 4,551 thrombolyzed AIS patients (mean age 66.7 years, 37.8% female), there were 65.4% Asians who were younger, fewer female, and with less atrial fibrillation, hypercholesterolemia, premorbid symptoms, and concomitant antihypertensive, antithrombotic and statin treatment, and more prior stroke, compared to non-Asians. Frequencies of hypertension, coronary artery disease, and diabetes mellitus were comparable between groups. Asian patients were less likely to be admitted to an acute stroke unit and receive early mobilization by a therapist or rehabilitation but more likely to receive intensive care. There were no significant differences between Asians and non-Asians in functional outcome (defined by mRS scores 2–6 or 3–5; adjusted odds ratio [OR] 1.00, 95% confidence interval [CI] 0.85–1.19 [p = 0.958] and OR 0.95, 95% CI 0.80–1.13 [p = 0.572], respectively), or death (OR 1.25, 95% CI 0.95–1.65; p = 0.116), despite Asians having greater odds of ICH (OR 1.51, 95% CI 1.23–1.86; p = 0.0001) and neurological deterioration within 24 h (OR 1.58, 95% CI 1.18–2.12; p = 0.002). Conclusions: Within the context of an international clinical trial of thrombolyzed AIS patients, demography, risk factors, management, and odds of early neurological deterioration and ICH, all differ between Asian and non-Asian participants. However, patterns of functional recovery are similar between these major regional groups. [ABSTRACT FROM AUTHOR]

BackgroundLesion patterns may predict prognosis after acute ischemic stroke within the middle cerebral artery (MCA) territory; yet it remains unclear whether such imaging prognostic factors are related to patient outcome after intravenous thrombolysis.AimsThe aim of this study is to investigate the clinical outcome after intravenous thrombolysis in acute MCA ischemic strokes with respect to diffusion-weighted imaging (DWI) lesion patterns.MethodsConsecutive acute ischemic stroke cases of the MCA territory treated over a 7-year period were retrospectively analyzed. All acute MCA stroke patients underwent a MRI scan before intravenous thrombolytic therapy was included. DWI lesions were divided into 6 patterns (territorial, other cortical, small superficial, internal border zone, small deep, and other deep infarcts). Lesion volumes were measured by dedicated imaging processing software. Favorable outcome was defined as modified Rankin scale (mRS) of 0-2 at 90 days.ResultsAmong the 172 patients included in our study, 75 (43.6%) were observed to have territorial infarct patterns or other deep infarct patterns. These patients also had higher baseline NIHSS score (p < 0.001), a higher proportion of large cerebral artery occlusions (p < 0.001) and larger infarct volume (p < 0.001). Favorable outcome (mRS 0-2) was achieved in 89 patients (51.7%). After multivariable analysis, groups with specific lesion patterns, including territorial infarct and other deep infarct pattern, were independently associated with favorable outcome (OR 0.40; 95% CI 0.16-0.99; p = 0.047).ConclusionsSpecific lesion patterns predict differential outcome after intravenous thrombolysis therapy in acute MCA stroke patients.

Background: The COVID-19 pandemic lockdown (CPL) lead to a significant decrease in emergency admissions worldwide. We performed a timely analysis of ischemic stroke (IS) and related consultations using the telestroke TEMPiS "working diagnosis" database prior (PL), within (WL), and after easing (EL) of CPL. Methods: Twelve hospitals were selected and data analyzed regarding IS (including intravenous thrombolysis [intravenous recombinant tissue plasminogen; IV rtPA] and endovascular thrombectomy [EVT]) and related events from February 1 to June 15 during 2017–2020. In addition, we aimed to correlate events to various mobile phone mobility data. Results: Following the significant reduction of IS, IV rtPA, and EVT cases during WL compared to PL in 2020 longitudinally (p values <0.048), we observed increasing numbers of consultations, IS, recommendations for EVT, and IV rtPA with the network in EL over WL not reaching PL levels yet. Absolute numbers of all consultations paralleled best to mobility data of public transportation over walking and driving mobility. Conclusions: While the decrease in emergency admissions including stroke during CPL can only be in part attributed by patients not seeking medical attention, stroke awareness in the pandemic, and direct COVID-19 triggered stroke remains of high importance. The number of consultations in TEMPiS during the lockdown parallels best with mobility of public transportation. As a consequence, exposure to common viruses, well-known triggers for acute cerebrovascular events and other diseases, are reduced and may add to the decline in stroke consultations. Further studies comparing national responses toward the course of the COVID-19 pandemic and stroke incidences are needed. [ABSTRACT FROM AUTHOR]

Background: The evolution of the symptomatic intracranial occlusion during transfers from primary stroke centers (PSCs) to comprehensive stroke centers (CSCs) for endovascular treatment (EVT) is not widely known. Our aim was to identify factors related to partial or complete recanalization (REC) at CSC arrival in patients with a documented large vessel occlusion (LVO) in PSC transferred for EVT evaluation to better define the workflow at CSC of this group of patients. Methods: We conducted an observational, multicenter study from a prospective, government-mandated, population-based registry of stroke patients with documented LVO at PSC transferred to CSC for EVT from January 2017 to June 2019. The primary end point was defined as partial or complete REC that precluded EVT at CSC arrival (REC). We evaluated the association between baseline, treatment variables and time intervals with the presence of REC. Results: From 589 patients, the rate of REC at CSC was 10.5% in all LVO patients transferred from PSC to CSC for EVT evaluation. On univariate analysis, lower PSC-NIHSS (median 12vs.16, p = 0.001), tPA treatment at PSC (13.7 vs. 5.0%; p = 0.001), presence of M2 occlusion on PSC (16.8 vs. 9%; p = 0.023), and clinical improvement at CSC arrival (21.7 vs. 9.6% p = 0.001) were associated with REC at CSC. On multivariate analysis, clinical improvement at CSC arrival (p < 0.001, OR: 5.96 95% CI: 2.5–13.9) and PSC tPA treatment predicted REC (p = 0.003, OR: 4.65, 95% CI: 1.73–12.4). Conclusion: REC at CSC arrival occurs exceptionally in patients with a documented LVO on PSC. Repeating a second vascular study before EVT would not be necessary in most patients. Despite its modest effect, tPA treatment at PSC was an independent predictor of REC. [ABSTRACT FROM AUTHOR]

Background and Purpose: The influence of specific brain lesions on health-related quality of life (HRQoL) after acute ischemic stroke (AIS) is uncertain. We aimed to identify imaging predictors of poor HRQoL in alteplase-treated participants of the alteplase dose arm of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Methods: ENCHANTED was an international trial of low- versus standard-dose intravenous alteplase in AIS patients, with functional outcome (modified Rankin scale [mRS]) and HRQoL on the 5-dimension European Quality of Life Scale (EQ-5D) assessed at 90 days post-randomization. Brain images were analyzed centrally by trained assessors. Multivariable logistic regression was undertaken in the study population randomly divided (2:1) into training (development) and validation (performance) groups, with age (per 10-year increase), ethnicity, baseline National Institutes of Health Stroke Scale (NIHSS) score, diabetes mellitus, premorbid function (mRS score 0 or 1), and proxy respondent, forced into all models. Data are presented with odds ratios (ORs) and 95% confidence intervals (CIs). Results: Eight prediction models were developed and validated in 2,526 AIS patients (median age 67.5 years; 38.4% female; 61.7% Asian) with complete brain imaging and 90-day EQ-5D utility score data. The best performance model included acute ischemic changes in the right (OR 1.69, 95% CI: 1.24–2.29) and deep (OR 1.50, 95% CI: 1.03–2.19) middle cerebral artery (MCA) regions. Several background features of brain frailty – atrophy, white matter change, and old infarcts – were significantly associated with adverse physical but not emotional HRQoL domains. Conclusions: In thrombolysed AIS patients, right-sided and deep ischemia within the MCA territory predict poor overall HRQoL, whilst features of old cerebral ischemia are associated with reduced physical HRQoL. [ABSTRACT FROM AUTHOR]

Background: Acute stroke patients are usually transported to the nearest hospital regardless of their required level of care. This can lead to increased pressure on emergency departments and treatment delay. Objective: The aim of the study was to explore the benefit of a mobile stroke unit (MSU) in the UK National Health Service (NHS) for reduction of hospital admissions. Methods: Prospective cohort audit observation with dispatch of the MSU in the East of England Ambulance Service area in Southend-on-Sea was conducted. Emergency patients categorized as code stroke and headache were included from June 5, 2018, to December 18, 2018. Rate of avoided admission to the accident and emergency (A&E) department, rate of admission directly to target ward, and stroke management metrics were assessed. Results: In 116 MSU-treated patients, the following diagnoses were made: acute stroke, n = 33 (28.4%); transient ischaemic attacks, n = 13 (11.2%); stroke mimics, n = 32 (27.6%); and other conditions, n = 38 (32.8%). Pre-hospital thrombolysis was administered to 8 of 28 (28.6%) ischaemic stroke patients. Pre-hospital diagnosis avoided hospital admission for 29 (25.0%) patients. As hospital treatment was indicated, 35 (30.2%) patients were directly triaged to the stroke unit, 1 patient (0.9%) even directly to the catheter laboratory. Thus, only 50 (43.1%) patients required transfer to the A&E department. Moreover, the MSU enabled thrombolysis with a median dispatch-to-needle time of 42 min (interquartile range, 40–60). Conclusion: This first deployment of an MSU in the UK NHS demonstrated improved triage decision-making for or against hospital admission and admission to the appropriate target ward, thereby reducing pressure on strained A&E departments. [ABSTRACT FROM AUTHOR]

Background and Aim: The risk/benefit profile of intravenous thrombolysis (IVT) prior to endovascular thrombectomy (EVT) in acute ischemic stroke is still unclear. We provide a systematic review and meta-analysis including studies comparing direct EVT (dEVT) vs. bridging treatment (IVT + EVT), defining the impact of treatment timing and eligibility to IVT on functional status and mortality. Methods: Protocol was registered with PROSPERO (CRD42019135915) and followed PRISMA guidelines. PubMed, EMBASE, and Cochrane Central were searched for randomized controlled trials (RCTs), retrospective, and prospective studies comparing IVT + EVT vs. dEVT in adults (≥18) with acute ischemic stroke. Primary endpoint was functional independence at 90 days (modified Rankin Scale <3); secondary endpoints were (i) good recanalization (thrombolysis in cerebral infarction >2a), (ii) mortality, and (iii) symptomatic intracranial hemorrhage (sICH). Subgroup analysis was performed according to study type, eligibility to IVT, and onset-to-groin timing (OGT), stratifying studies for similar OGT. ORs for endpoints were pooled with meta-analysis and compared between reperfusion strategies. Results: Overall, 35 studies were included (n = 9,117). No significant differences emerged comparing patients undergoing dEVT and bridging treatment for gender, hypertension, diabetes, National Institute of Health Stroke Scale score at admission. Regarding primary endpoint, IVT + EVT was superior to dEVT (OR 1.44, 95% CI 1.22–1.69, p < 0.001, pheterogeneity<0.001), with number needed to treat being 18 in favor of IVT + EVT. Results were confirmed in studies with similar OGT (OR 1.66; 95% CI 1.21–2.28), shorter OGT for IVT + EVT (OR 1.53, 95% CI 1.27–1.85), and independently from IVT eligibility (OR 1.53, 95% CI 1.29–1.82). Mortality at 90 days was higher in dEVT (OR 1.38; 95% CI 1.09–1.75), but no significant difference was noted for sICH. However, considering data from RCT only, reperfusion strategies had similar primary (OR 0.91, 95% CI 0.6–1.39) and secondary endpoints. Differences in age and clinical severity across groups were unrelated to the primary endpoint. Conclusions: Compared to dEVT, IVT + EVT associates with better functional outcome and lower mortality. Post hoc data from RCTs point to substantial equivalence of reperfusion strategies. Therefore, an adequately powered RCTs comparing dEVT versus IVT + EVT are warranted. [ABSTRACT FROM AUTHOR]

Objective: To determine the extent to which the effects of intensive blood pressure (BP) lowering are modified by doses of alteplase in thrombolysis-eligible acute ischemic stroke (AIS) patients. Methods: Prespecified analyses of the Enhanced Control of Hypertension and Thrombolysis Stroke Study for patients enrolled in both arms: (i) low-dose (0.6 mg/kg body weight) or standard-dose (0.9 mg/kg) alteplase and (ii) intensive (target systolic BP [SBP] 130–140 mm Hg) or guideline-recommended (target SBP <180 mm Hg) BP management. The primary outcome was functional recovery, measured by a shift in scores on modified Rankin scale at 90 days. The safety outcome was any intracranial hemorrhage (ICH). Results: There were 925 participants (mean age 67 years, 39% female, 77% Asian) randomized to both arms: 242 randomly assigned to guideline/standard-dose (GS); 234 to guideline/low-dose (GL); 227 to intensive/standard-dose (IS); and 222 to intensive/low-dose (IL). Overall, average SBP levels within 24 h were lower in the low-dose compared to standard-dose alteplase group (146 and 144 vs. 151 and 150 mm Hg, for GS and GL vs. IS and IL, respectively, p < 0.0001). There was no heterogeneity of the effects of BP lowering (intensive vs. guideline) on functional recovery between standard-dose (OR 0.81, 95% CI 0.59–1.12) and low-dose alteplase (1.06, 0.77–1.47; p = 0.25 for interaction). Similar results were observed for ICH (p = 0.50 for interaction). Conclusions: In thrombolysis-treated patients with predominantly mild-to-moderate severity AIS, intensive BP lowering neither improve functional recovery, either with low- or standard-dose intravenous alteplase, nor beneficially interact with low-dose alteplase in reducing ICH. Trial Registration: The trial is registered with ClinicalTrials.gov (NCT01422616). [ABSTRACT FROM AUTHOR]

Introduction: The management of acute ischemic stroke in patients on direct oral anticoagulants (DOACs) is challenging. However, the substance-specific plasma level could guide treatment decisions on recanalization therapies. We present a plasma-level-based protocol for emergency treatment of stroke patients on oral anticoagulants. Bleeding complications and clinical outcome for patients on DOACs are reported and compared to patients on vitamin K antagonists (VKAs). Methods: In patients with acute ischemic stroke and suspected use of DOACs within 48 h prior to hospital admission, plasma levels were measured using the calibrated Xa-activity (apixaban, edoxaban, rivaroxaban) or the Hemoclot®-assay (dabigatran). Levels <50 ng/mL were supportive for thrombolysis, while high values >100 ng/mL excluded patients from recombinant tissue plasminogen activator use. For patients on VKAs, the cutoff was set at international normalized ratio of 1.7. Endovascular thrombectomy of a large vessel occlusion was performed independently from coagulation testing. Consecutive patients were included in an observational registry. Results: Five hundred and twenty-two patients (261 on VKAs and 261 on DOACs) were included. Thirty patients (11.5%) on VKAs and 24 (9.2%) on DOACs received thrombolysis, followed by mechanical thrombectomy in 10 and 14 patients, respectively. Seventeen patients in each group received thrombectomy only. Symptomatic intracranial hemorrhage associated with thrombolysis occurred in 1 patient on VKA (3.3%) and 1 on DOAC (4.2%; p = 0.872). The turnaround time of specific assays did not show a significant delay in comparison to standard coagulation parameters. Conclusion: DOAC plasma levels could support decisions on emergency treatment of ischemic stroke. Systemic thrombolysis below suggested thresholds appears preliminary feasible and safe without an excess in bleeding complications. [ABSTRACT FROM AUTHOR]

Background and Objectives: This paper aims to describe and compare the characteristics of 2 stroke populations in Singapore and in St. Louis, USA, and to document thrombolysis rates and contrast factors associated with its uptake in both populations. Methods: The stroke populations described were from the Singapore Stroke Registry (SSR) in -Singapore and the Cognitive Rehabilitation Research Group Stroke Registry (CRRGSR) in St. Louis, MO, USA. The registries were compared in terms of demographics and stroke risk factor history. Logistic regression was used to determine factors associated with thrombolysis uptake. Results: A total of 39,323 and 8,106 episodes were recorded in SSR and CRRGSR, respectively, from 2005 to 2012. Compared to CRRGSR, patients in SSR were older, male, and from the ethnic majority. Thrombolysis rates in SSR and CRRGSR were 2.5 and 8.2%, respectively, for the study period. History of ischemic heart disease or atrial fibrillation was associated with increased uptake in both populations, while history of stroke was associated with lower uptake. For SSR, younger age and males were associated with increased uptake, while having a history of smoking or diabetes was associated with decreased uptake. For CRRGSR, ethnic minority status was associated with decreased uptake. Conclusions: The comparison of stroke populations in Singapore and St Louis revealed distinct differences in clinicodemographics of the 2 groups. Thrombolysis uptake was driven by nonethnicity demographics in Singapore. Ethnicity was the only demographic driver of uptake in the CRRGSR population, highlighting the need to target ethnic minorities in increasing access to thrombolysis. [ABSTRACT FROM AUTHOR]

Background/Aim: Endovascular thrombectomy may be performed in anticoagulated patients taking vitamin-K antagonists (VKA) or direct-acting oral anticoagulants (DOAC) in whom the use of intravenous tissue plasminogen activator (tPA) is contraindicated. We aimed to investigate the efficacy and safety of mechanical thrombectomy specifically in anticoagulated patients ineligible for thrombolysis. Methods: We performed a retrospective analysis of a prospectively collected database of consecutive ischaemic stroke patients undergoing mechanical thrombectomy from January 2008 to June 2017. Patients receiving any dose of intravenous or intra-arterial thrombolysis were excluded. Patients taking oral anticoagulants (VKAs or DOACs) were compared with non-anticoagulated patients. Outcomes compared between groups included the rate of intracerebral haemorrhage (ICH) on follow-up imaging (ICHany), symptomatic ICH, functional independence at 90 days (modified Rankin scale score, 0–2), mortality, and post-treatment recanalization (Thrombolysis in Cerebral Infarction score ≥2b). Results: In all, 102 patients undergoing mechanical thrombectomy without prior thrombolysis were included in the study. Sixty-six (64.7%) patients were not anticoagulated, 23 (22.5%) patients were taking VKAs, and 13 (12.7%) patients were taking DOACs. There were no significant differences in the rate of ICHany (11.1 vs. 13.6%, p = 0.93) or sICH (2.8 vs. 1.5%, p = 0.14) in anticoagulated patients compared to non-anticoagulated patients. No cases of sICH were observed among patients taking DOACs. After 90 days of follow-up, the rates of functional independence (50.0 vs. 43.1%) and mortality (27.8 vs. 25.8%) were also similar between the anticoagulation and the non-anticoagulation groups. Conclusion: Mechanical thrombectomy appears to be safe and effective in anticoagulated patients ineligible for thrombolysis, with observed haemorrhage rates similar to those of patients not on anticoagulant therapy. However, further multicentre prospective studies are needed, due to the rising number of patients on warfarin and DOACs worldwide. [ABSTRACT FROM AUTHOR]

Objectives: The study aimed to evaluate the impact of a telestroke network on acute stroke care in Catalonia, by measuring thrombolysis rates, access to endovascular treatment, and clinical outcome of telestroke patients in a population-based study. Methods: Telestroke network was implemented on March 2013 and consists of 12 community hospitals and 1 expert stroke neurologist 24 h/7 day, covering a population of 1.3 million inhabitants. Rest of the population (6.2 million) of Catalonia is covered by 8 primary stroke centers (PSC) and 6 comprehensive stroke centers (CSC). After a 2-way videoconference and visualization of neuroimaging on a web platform, the stroke neurologist decides the therapeutic approach and/or to transfer the patient to another facility, entering these data in a mandatory registry. Simultaneously, all patients treated with reperfusion therapies in all centers of Catalonia are prospectively recorded in a mandatory and audited registry. Results: From March 2013 to December 2015, 1,206 patients were assessed by telestroke videoconference, of whom 322 received intravenous thrombolysis (IVT; 33.8% of ischemic strokes). Baseline and 24 h NIHSS, rate of symptomatic hemorrhage, mortality, and good outcome at 3 months were similar compared to those who received IVT in PSC or CSC (2,897 patients in the same period). The door-to-needle time was longer in patients treated through telestroke, but was progressively reduced from 2013 to 2015. Percentage of patients receiving thrombectomy after IVT was similar in patients treated through telestroke circuit, compared to those treated in PSC or CSC (conventional circuit). Population rates of IVT*100,000 inhabitants in Catalonia increased from 2011 to 2015, especially in areas affected by the implementation of telestroke network, achieving rates as high as 16 per 100,000 inhabitants. Transfers to another facility were avoided after telestroke consultation in 46.8% of ischemic, 76.5% of transient ischemic attacks, and 23.5% of hemorrhages. Conclusions: Telestroke favors safe and effective thrombolysis, helps to increase the population rate of IVT, and avoids a large number of interhospital transfers. [ABSTRACT FROM AUTHOR]

Background: The actions and responses of the hospital personnel during acute stroke care in the emergency department (ED) may differ according to the severity of a patient's stroke symptoms. We investigated whether the time from arrival at ED to various care steps differed between patients with minor and non-minor stroke who were treated with intravenous tissue plasminogen activator (IV tPA). Methods: We included consecutive patients who received IV tPA during a 1.5 year-period in 5 hospitals. Minor stroke was defined as a National Institutes of Health Stroke Scale (NIHSS) score < 5. We compared various intervals from arrival at the ED to treatment between patients with minor stroke and those with non-minor stroke (NIHSS score ≥5). Delayed treatment was defined as a door-to-needle time > 40 min. Results: During the study period, 356 patients received IV tPA treatment. The median door-to-needle time was significantly longer in the minor stroke group than it was in the non-minor stroke group (43 min [interquartile range [IQR] 35.5–55.5] vs. 37 min [IQR 30–46], p < 0.001). The minor stroke group had a significantly longer door-to-notification time (7 min [IQR 4.5–12] vs. 5 min [IQR 3–8], p < 0.001) and door-to-imaging time (20 min [IQR 15–26.5] vs. 16 min [IQR 11–21], p < 0.001) than did the non-minor stroke group. However, the imaging-to-needle time was not different between the groups. Multivariable analyses revealed that minor stroke was associated with delayed treatment (OR 2.54 [95% CI 1.52–4.30], p = 0.001). Conclusions: Our findings show that the door-to-needle time was longer in patients with minor stroke than it was in those with non-minor stroke, mainly owing to delayed action in the initial steps of neurology notification and imaging. Our findings suggest that some quality improvement initiatives are necessary for patients with suspected stroke with minor symptoms. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to demonstrate that the median door-to-needle (DTN) time for intravenous tissue plasminogen activator (tPA) treatment can be reduced to 45 min in a primary stroke centre with MRI-based screening for acute ischaemic stroke (AIS). Methods: From February 2015 to February 2017, the stroke unit of Perpignan general hospital, France, implemented a quality-improvement (QI) process. During this period, patients who received tPA within 4.5 h after AIS onset were included in the QI cohort. Their clinical characteristics and timing metrics were compared each semester and also with those of 135 consecutive patients with AIS treated by tPA during the 1-year pre-QI period (pre-QI cohort). Results: In the QI cohort, 274 patients (92.5%) underwent MRI screening. While the demographic and baseline characteristics were not significantly different between cohorts, the median DTN time was significantly lower in the QI than in the pre-QI cohort (52 vs. 84 min; p < 0.00001). Within the QI cohort, the median DTN time for each semester decreased from 65 to 44 min (p < 0.00001) and the proportion of treated patients with a DTN time ≤45 min increased from 25 to 58.9% (p < 0.0001). Overall, DTN time improvement was associated with a better outcome at 3 months (patients with a modified Rankin Scale score between 0 and 2: 61.8% in the QI vs. 39.3% in the pre-QI cohort; p < 0.0001). Conclusions: A QI process can reduce the DTN within 45 min with MRI as a screening tool. [ABSTRACT FROM AUTHOR]

Background and Purpose: Driven by the positive results of randomized, controlled trials of endovascular stroke therapies (EVT) in stroke patients with large vessel occlusion, different approaches to speed up the workflow for EVT candidates are currently being implemented worldwide. We aimed to assess the effect of a simple stroke network-wide workflow improvement project, primarily focusing on i.v. thrombolysis, on process times for patients undergoing EVT. Methods: In 2015, we conducted a network-wide, peer-to-peer acute stroke workflow improvement program for i.v. thrombolysis with the main components of implementing a binding team-based algorithm at every stroke unit of the regional network, educating all stroke teams about non-technical skills and providing a stroke-specific simulation training. Before and after the intervention we recorded periprocedural process times, including patients undergoing EVT at the 3 EVT-capable centers (January – June 2015, n = 80 vs. July 2015 – June 2016, n = 184). Results: In this multi-centric evaluation of 268 patients receiving EVT, we observed a relevant shortening of the median time from symptom onset to EVT specifically in patients requiring secondary transfer by almost an hour (300 min, 25–75% interquartile range [IQR] 231–381 min to 254 min, IQR 215.25–341 min; p = 0.117), including a reduction of the median door-to-groin time at the EVT-capable center in this patient group by 15.5 min (59 min, IQR 35–102 min to 43.5 min, IQR 27.75–81.25 min; p = 0.063). In patients directly admitted to an EVT-capable center, the median door-to-groin interval was reduced by 10.5 min (125 min, IQR 83.5–170.5 min to 114.5 min, IQR 66.5–151 min; p = 0.167), but a considerable heterogeneity between the centers was observed (p < 0.001). Conclusions: We show that a simple network-wide workflow improvement program primarily directed at fast i.v. thrombolysis also accelerates process times for EVT candidates and is a promising measure to improve the performance of an entire stroke network. [ABSTRACT FROM AUTHOR]

Background: Renal dysfunction (RD) may be associated with poor outcome in ischemic stroke patients treated with mechanical thrombectomy (MT), but data concerning this important and emerging comorbidity do not exist so far. Here, we investigated the influence of RD on postprocedural intracerebral hemorrhage (ICH), clinical outcome, and mortality in a large prospectively collected cohort of acute ischemic stroke patients treated with MT. Methods: Consecutive patients with anterior-circulation stroke treated with MT between October 2010 and January 2016 were included. RD was defined as glomerular filtration rate (GFR) <60 mL/min/1.73 m². In a prospective database, clinical characteristics were recorded and brain images were analyzed for the presence of ICH after treatment in all patients. Clinical outcome was assessed by the modified Rankin Scale (mRS) after 3 months. To evaluate associations between clinical factors and outcomes uni- and multivariate regression analyses were conducted. Results: In total, 505 patients fulfilled all inclusion criteria (female: 49.7%, mean age: 71.0 years). RD at admission was present in 20.2%. RD patients were older and had cardiovascular risk factors more often. Multivariate regression analysis after adjustment for age, stroke severity, diabetes, hypertension, GFR, previous stroke, MT alone, or additional thrombolysis and recanalization results revealed that lower GFR was not independently associated with poor outcome (mRS 3-6; OR 1.13, 95% CI 0.99-1.28; p = 0.072) or ICH. However, lower GFR at admission was associated with a higher risk of mortality (OR 1.15, 95% CI 1.01-1.31; p = 0.038). Compared to admission, GFR values were higher at discharge (mean: 77.9 vs. 80.8 mL/min/1.73 m²; p = 0.046). Conclusions: We did not find evidence for an association of lower GFR with an increased risk of poor outcome and ICH, but lower GFR was a determinant of 90-day mortality after endovascular stroke treatment. Our findings encourage also performing MT in this relevant subgroup of acute ischemic stroke patients. [ABSTRACT FROM AUTHOR]

Background and Purpose: Thrombin-activatable fibrinolysis inhibitor (TAFI) activation following thrombolysis may affect thrombolysis effectiveness in acute ischemic stroke (AIS). To support this hypothesis, we propose to study the relationship between TAFI consumption, activated/inactivated TAFI (TAFIa/ai) and stroke severity and outcome in 2 groups of AIS patients, one treated and one untreated with intravenous recombinant tissue type plasminogen activator (rt-PA). Methods: In this prospective, longitudinal, multicenter, observational study, we aimed to study the association between TAFIa/ai and stroke outcome. TAFI levels were sequentially measured in patients treated with intravenous rt-PA thrombolysis (T), and in patients not given any thrombolytic therapy (NT). Baseline reference values were established in healthy subjects matched for age and gender. The National Institutes of Health Stroke Scale (NIHSS) score assessed at baseline and on day 2 was dichotomized into 2 severity groups (0-7 vs. >7). The modified Rankin Scale (mRS) score at day 90 was dichotomized for favorable (0-1) and unfavorable (2-6) outcomes. Results: A total of 109 patients were included, with 41 receiving rt-PA. At admission, patients had higher TAFIa/ai levels than reference. A significant increase in TAFIa/ai levels was observed at the end of thrombolysis (mean change from baseline of 963%) and lasted up to 4 h (191%). Higher TAFIa/ai levels were associated with a more severe day 2 NIHSS score (p = 0.0098 at T2h post thrombolysis) and an unfavorable mRS score from T48h (p = 0.0417) to day 90 (p = 0.0046). In NT patients, higher TAFIa/ai levels at admission were associated with a more severe stroke, as assessed by day 2 NIHSS score (p = 0.0026) and mRS score (p = 0.0003). Conclusion: These data demonstrate a consistent relationship between TAFI levels and early clinical severity during rt-PA treatment. [ABSTRACT FROM AUTHOR]

Background: There has been no large-scale trial comparing endovascular treatment (add-on EVT) after intravenous tissue plasminogen activator (IV tPA) and IV tPA alone in acute ischemic stroke (AIS) caused by internal carotid artery occlusion (ICAO). We aimed at investigating the effectiveness and safety of add-on EVT after IV tPA in AIS patients with ICAO. Methods: Between March 2010 and March 2013, 3,689 consecutive ischemic stroke patients who were hospitalized within 4.5 h of onset were identified using a prospective stroke registry at 11 centers in Korea. Among them, patients with persistent ICAO after receiving IV tPA and whose 3-month modified Rankin Scale (mRS) was available were finally enrolled. A propensity score analysis with inverse-probability of treatment weighting was used to eliminate baseline imbalances between those receiving add-on EVT and IV tPA alone. Results: Among 264 patients enrolled in this study (mean age 71.4; male 56.4%; median National Institute of Health Stroke Scale score 15), 117 (44.3%) received add-on EVT. The add-on EVT group had a higher frequency of favorable outcome on the mRS ≤ 2 (35.0 vs. 18.4%; adjusted OR (aOR) 2.79; 95% CI 1.66-4.67) and lower mortality (17.9 vs. 35.4%; aOR 0.24; 95% CI 0.13-0.42) at 3 months, when compared to the IV tPA-alone group. Add-on EVT did not significantly increase the risk of symptomatic hemorrhage (5.1 vs. 4.1%; aOR 1.01; 95% CI 0.37-2.70). The rate of successful recanalization (thrombolysis in cerebral infarction grade ≥ 2b) in the add-on EVT group was 69.2%. Conclusions: Compared to an IV tPA alone, add-on EVT can improve clinical outcomes in patients with symptomatic ICAO within 4.5 h of onset without a significant increase of symptomatic hemorrhage. [ABSTRACT FROM AUTHOR]

Background: The Preventive Antibiotics in Stroke Study (PASS), a randomized open-label masked endpoint trial, showed that preventive ceftriaxone did not improve functional outcome at 3 months in patients with acute stroke (adjusted common OR 0.95; 95% CI 0.82-1.09). Post-hoc analyses showed that among patients who received intravenous thrombolysis (IVT), patients who received ceftriaxone had a significantly better outcome as compared with the control group. This study aimed to gain more insight into the characteristics of these patients. Methods: In PASS, 2,550 patients were randomly assigned to preventive antibiotic treatment with ceftriaxone or standard care. In current post-hoc analysis, 836 patients who received IVT were included. Primary outcome included functional status on the modified Rankin Scale, analyzed with adjusted ordinal regression. Secondary outcomes included infection rate and symptomatic intracerebral hemorrhage (sICH) rate. Results: For all patients in PASS, the p value for the interaction between IVT and preventive ceftriaxone regarding functional outcome was 0.03. Of the 836 IVT-treated patients, 437 were administered ceftriaxone and 399 were allocated to the control group. Baseline characteristics were similar. In the IVT subgroup, preventive ceftriaxone was associated with a significant reduction in unfavorable outcome (adjusted common OR 0.77; 95% CI 0.61- 0.99; p = 0.04). Mortality at 3 months was similar (OR 0.75; 95% CI 0.48-1.18). Preventive ceftriaxone was associated with a reduction in infections (OR 0.43; 95% CI 0.28-0.66), and a trend towards an increased risk for sICH (OR 3.09; 95% CI 0.85-11.31). Timing of ceftriaxone administration did not influence the outcome (aOR 1.00; 95% CI 0.98-1.03; p = 0.85). Conclusions: According to the post-hoc analysis of PASS, preventive ceftriaxone may improve the functional outcome in IVT-treated patients with acute stroke, despite a trend towards an increased rate of post-IVT-sICH. [ABSTRACT FROM AUTHOR]

Background: Although thrombolysis is considered to be the first-line treatment for ischemic stroke, there remains an ongoing controversy on the safety and efficacy of thrombolysis in cervical artery dissection (CAD). The aim of this meta-analysis was to assess observational data related to the safety and efficacy of thrombolysis in CAD-related ischemic stroke. Methods: We performed a systematic search of the efficacy of thrombolysis treatment in CAD-related ischemic stroke with appropriate observational studies identified for the study. The meta-analysis models in Comprehensive Meta-Analysis V2 software were applied to calculate the merged rates of favorable outcome (modified Rankin Scale, mRS 0-2), excellent outcome (mRS 0-1), intracranial hemorrhage (ICH), symptomatic ICH (SICH), mortality and recurrent stroke between thrombolysis and non-thrombolysis in CAD-related stroke. The difference of outcomes and adverse events between the 2 groups was compared by analyzing the pooled OR value and chi-square test using the software SPSS. Results: A total of 846 patients were identified from 10 studies (174 with thrombolysis; 672 with non-thrombolysis). The meta-analysis detected no significant statistical difference in the proportion of CAD-related stroke patients enjoying a favorable outcome at the 3 months' follow-up between the thrombolysis and non-thrombolysis groups (53.7 vs. 58.2%, OR 0.782, χ 2 = 0.594, p > 0.05); non-thrombolysis was slightly superior than thrombolysis in terms of excellent outcome (52.4 vs. 34.4%, OR 0.489, χ 2 = 9.143, p = 0.002). There was no significant difference in SICH, mortality and recurrent stroke rates between the 2 groups (all p > 0.05). ICH rate was higher in the thrombolysis group of CAD-related stroke patients compared to that in the non-thrombolysis group (12.3 vs. 7.4%, OR 2.647, χ 2 = 4.127, p = 0.042). Conclusion: Thrombolysis seems to be equally safe and will achieve an efficacy similar to the efficacy of non-thrombolysis in patients with acute ischemic stroke due to CAD. It is also as effective as thrombolysis in stroke from miscellaneous causes. Therefore, CAD patients experiencing a stroke should not be denied thrombolysis therapy. However, this will need to be confirmed in large-scale randomized studies, especially involving intravenous thrombolysis treatment. [ABSTRACT FROM AUTHOR]

Background: Body weight and body mass index (BMI) are regularly assessed factors in stroke patients for manifold reasons. However, their potential role specifically in intravenous thrombolysis has not been thoroughly examined. Methods: Data from 865 consecutive acute ischemic stroke patients treated with intravenous thrombolysis were analyzed. Patients were divided into different BMI categories (underweight, normal weight, overweight, obese) and compared based on the following factors: time window of treatment, clinical scores National Institute of Health Stroke Scale Score (NIHSS), modified Rankin scale (mRS) on admission and discharge, risk factors, stroke characteristics and thrombolysis complications. Recombinant tissue plasminogen activator (rtPA) doses relative to body weight and blood volume were also assessed. In a separate analysis, patients weighing up to 100 and >100 kg were compared. Results: Eighteen patients (2.1%) were underweight, 336 (38.8%) overweight, 194 (22.4%) obese and 317 (36.7%) had normal weight. Higher BMI category was associated with younger age, thrombolytic treatment later than 4.5 h, arterial hypertension, diabetes and higher relative rtPA dose relative to blood volume (p < 0.001). There were no significant differences concerning NIHSS and mRS scores or thrombolysis complications. Fortysix patients (5.3%) weighed over 100 kg. They were younger (p = 0.002) and treated later than patients under 100 kg (p < 0.001). Mean rtPA dose relative to body weight and to blood volume was significantly lower (0.7 vs. 0.9 mg/kg, p < 0.001 and 13 vs. 13.9 mg/l, p < 0.001). There was a marginal difference in NIHSS score improvement ≥ 4 points (26.1 vs. 40.2%, p = 0.038); otherwise, no outcome differences were found. Conclusion: BMI category does not significantly influence clinical outcome after thrombolysis. However, relevant NIHSS improvement was found more often in patients weighing up to 100 kg compared to those over 100 kg. Interestingly, patients with higher BMI or weight >100 kg were thrombolysed later than other patients. [ABSTRACT FROM AUTHOR]

Background: In the last 12 months, treatment of acute ischaemic stroke secondary to large vessel occlusion has undergone a paradigm shift. The success of endovascular surgery, and in particular, the use of stent-retrievers, is remarkable. Summary: Beyond percentages and p values, the endovascular trials demonstrated, in their similarities and their differences, the critical elements of successful intervention in acute ischaemic stroke. Patient selection based on non-invasive neuroimaging has emerged as a critical step in acute ischaemic stroke management. The more sophisticated imaging-based selection, those assessing collateral blood flow or ischaemic penumbra appear to be associated with better outcomes and possibly fewer complications. The importance of achieving effective, quality reperfusion is also demonstrated, in a remarkably linear fashion, across the 5 published trials. This may emerge as the single most important determinant of functional outcomes. While reperfusion may succeed time as the preeminent modifiable variable, it remains clear that achieving quality reperfusion in a timely manner should remain the goal of all acute stroke programs. Key Message: Comparing the recent successful endovascular stroke trials, both between one another, and to their unsuccessful predecessors, emphasizes the importance of patient selection, time and reperfusion. Highlighting these factors allows for a better understanding of the challenges facing clinicians and the changes required to be made in hospital systems in order to achieve a new standard of care in treating acute ischaemic stroke. [ABSTRACT FROM AUTHOR]

Background and Purpose: Acute Stanford type A aortic dissection (AAD) is a devastating aortic disease, and prompt diagnosis is sometimes difficult to make. Identification of AAD in suspected acute stroke patients is especially challenging. Nevertheless, the frequencies and predictive factors of AAD in suspected acute stroke patients have not been well investigated. The aim of this study was to elucidate the prevalence of and predictors for AAD in patients with suspected acute stroke. Methods: From January 2012 through January 2013, consecutive patients who visited our emergency department (ED) due to suspected acute (<24 h from onset) stroke were retrospectively enrolled. Clinical parameters including systolic blood pressure (SBP) and laboratory data were collected. Frequency of AAD in suspected acute stroke patients and acute ischemic stroke (AIS) subjects were assessed, and factors associated with AAD among AIS patients were investigated. Results: A total of 1,637 patients were included in this study. Five patients (0.31%, 95% CI 0.04-0.57) were diagnosed as having AAD. The prevalence of AAD in all AIS individuals during the study period was 1.09% (95% CI 0.14- 2.05), and AAD accounted for 1.70% (95% CI 0.05-3.36) of AIS patients who appeared at the hospital within 4 h from onset. Most AAD patients presented with disturbed consciousness, and none of the AAD patients complained of chest pain. Neck ultrasonography detected an intimal flap in AAD patients. Two AAD cases died soon after ED arrival. The remaining 3 were promptly diagnosed as having AAD in the ED and underwent emergency surgery; all were discharged with only mild neurological symptoms. Low SBP in the right arm (cut-off value ≤ 110 mm Hg, sensitivity 100%, specificity 94.4%) and high D-dimer level (cut-off value ≥ 5.0 μg/ml, sensitivity 100%, specificity 91.7%) had high predictive values for detecting AAD in patients with AIS presenting within 4 h from onset. Conclusions: AAD was seen in 0.31% of suspected acute stroke patients and 1.70% of AIS patients presenting within 4 h from onset. AAD patients who were initially suspected as having acute stroke had severe neurological symptoms, including disturbance of consciousness, did not complain of typical chest pain, and when emergency surgery was performed, favorable neurological and survival outcomes were achieved. Low SBP in the right arm and high Ddimer level could predict AAD. [ABSTRACT FROM AUTHOR]

Objectives: Young adults with ischemic stroke may present late to medical care, but the reasons for these delays are unknown. We sought to identify factors that predict delay in presentation. Methods: We performed a retrospective cohort study of adults aged 18-50 admitted to a single academic medical center between 2007 and 2012. Results: Eighty six of 141 (61%) young adults with ischemic stroke presented at the health center more than 4.5 h after stroke onset. Diabetes was associated with delays in presentation (p = 0.033, relative risk (RR) 1.4 (95% CI 1.1-1.8)), whereas systemic cancer was associated with early presentations (p = 0.033, RR 0.26 (95% CI 0.044-1.6)). Individuals who were single were more likely to present late than those who were married or living with a partner (p = 0.0045, RR 1.7 (95% CI 1.3-2.2)). Individuals who were unemployed were more likely to present late than those who were employed or in school (p = 0.020, RR 1.4 (95% CI 1.1-1.8)). Age (dichotomized as 18-35 and 36-50), race, home medications, other medical conditions (including common stroke mimics in young adults), and stroke subtype were not determinants of delay in presentation, although there was a trend toward delayed presentations in women (p = 0.076) and with low stroke severity (dichotomized as National Institutes of Health Stroke Scale (NIHSS) ≤ 5 and NIHSS >5, p = 0.061). Conclusions: A majority of young adults with ischemic stroke presented outside the time window for intravenous fibrinolysis. Diabetes, single status, and unemployed status were associated with delayed presentation. [ABSTRACT FROM AUTHOR]