Frequency and Patterns of Brain Infarction in Patients With Embolic Stroke of Undetermined Source: NAVIGATE ESUS Trial.

BACKGROUND AND PURPOSE: The spectrum of brain infarction in patients with embolic stroke of undetermined source (ESUS) has not been well characterized. Our objective was to define the frequency and pattern of brain infarcts detected by magnetic resonance imaging (MRI) among patients with recent ESUS participating in a clinical trial. METHODS: In the NAVIGATE ESUS trial (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source), an MRI substudy was carried out at 87 sites in 15 countries. Participants underwent an MRI using a specified protocol near randomization. Images were interpreted centrally by those unaware of clinical characteristics. RESULTS: Among the 918 substudy cohort participants, the mean age was 67 years and 60% were men with a median (interquartile range) of 64 (26-115) days between the qualifying ischemic stroke and MRI. On MRI, 855 (93%) had recent or chronic brain infarcts that were multiple in 646 (70%) and involved multiple arterial territories in 62% (401/646). Multiple brain infarcts were present in 68% (510/755) of those without a history of stroke or transient ischemic attack before the qualifying ESUS. Prior stroke/transient ischemic attack (P<0.001), modified Rankin Scale score >0 (P<0.001), and current tobacco use (P=0.01) were associated with multiple infarcts. Topographically, large and/or cortical infarcts were present in 89% (757/855) of patients with infarcts, while in 11% (98/855) infarcts were exclusively small and subcortical. Among those with multiple large and/or cortical infarcts, 57% (251/437) had one or more involving a different vascular territory from the qualifying ESUS. CONCLUSIONS: Most patients with ESUS, including those without prior clinical stroke or transient ischemic attack, had multiple large and/or cortical brain infarcts detected by MRI, reflecting a substantial burden of clinical stroke and covert brain infarction. Infarcts most frequently involved multiple vascular territories. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02313909.

Ultrasonography Grading of Internal Carotid Artery Disease: Multiparametric German Society of Ultrasound in Medicine (DEGUM) versus Society of Radiologists in Ultrasound (SRU) Consensus Criteria.

PURPOSE: We sought to determine the diagnostic agreement between the revised ultrasonography approach by the German Society of Ultrasound in Medicine (DEGUM) and the established Society of Radiologists in Ultrasound (SRU) consensus criteria for the grading of carotid artery disease. MATERIALS AND METHODS: Post-hoc analysis of a prospective multicenter study, in which patients underwent ultrasonography and digital subtraction angiography (DSA) of carotid arteries for validation of the DEGUM approach. According to DEGUM and SRU ultrasonography criteria, carotid arteries were independently categorized into clinically relevant NASCET strata (normal, mild [1-49 %], moderate [50-69 %], severe [70-99 %], occlusion). On DSA, carotid artery findings according to NASCET were considered the reference standard. RESULTS: We analyzed 158 ultrasonography and DSA carotid artery pairs. There was substantial agreement between both ultrasonography approaches for severe (κw 0.76, CI95 %: 0.66-0.86), but only fair agreement for moderate (κw 0.38, CI95 %: 0.19-0.58) disease categories. Compared with DSA, both ultrasonography approaches were of equal sensitivity (79.7 % versus 79.7 %; p = 1.0) regarding the identification of severe stenosis, yet the DEGUM approach was more specific than the SRU approach (70.2 % versus 56.4 %, p = 0.0002). There was equality of accuracy parameters (p > 0.05) among both ultrasonography approaches for the other ranges of carotid artery disease. CONCLUSION: While the sensitivity was equivalent, false-positive identification of severe carotid artery stenosis appears to be more frequent when using the SRU ultrasonography approach than the revised multiparametric DEGUM approach.

Inadvertent hypothermia after endovascular therapy is not associated with improved outcome in stroke due to anterior circulation large vessel occlusion.

BACKGROUND AND PURPOSE: Hypothermia may be neuroprotective in acute ischemic stroke. Patients with anterior circulation large vessel occlusion (acLVO) are frequently hypothermic after endovascular therapy (EVT). We sought to determine whether this inadvertent hypothermia is associated with improved outcome. METHODS: We extracted data of consecutive patients (January 2016 to May 2019) who received EVT for acLVO from our prospective EVT register of all patients screened for EVT at our tertiary stroke center. We assessed functional outcome at 3 months and performed multivariate analysis to calculate adjusted risk ratios (aRRs) for favorable outcome (modified Rankin Scale scores = 0-2) and mortality across patients who were hypothermic (<36°C) and patients who were normothermic (≥36°C to <37.6°C) after EVT. Moreover, we compared the frequency of complications between these groups. RESULTS: Among 837 patients screened, 416 patients received EVT for acLVO and fulfilled inclusion criteria (200 [48.1%] male, mean age = 76 ± 16 years, median National Institutes of Health Stroke Scale score = 16, interquartile range [IQR] = 12-20). Of these, 209 patients (50.2%) were hypothermic (median temperature = 35.2°C, IQR = 34.7-35.7) and 207 patients were normothermic (median temperature = 36.4°C, IQR = 36.1-36.7) after EVT. In multivariate analysis, hypothermia was not associated with favorable outcome (aRR = 0.99, 95% confidence interval [CI] = 0.75-1.31) and mortality (aRR = 1.18, 95% CI = 0.84-1.66). More hypothermic patients suffered from pneumonia (36.4% vs. 25.6%, p = 0.02) and bradyarrhythmia (52.6% vs. 16.4%, p < 0.001), whereas thromboembolic events were distributed evenly (5.7% vs. 6.8%, not significant). CONCLUSIONS: Inadvertent hypothermia after EVT for acLVO is not associated with improved functional outcome or reduced mortality but is associated with an increased rate of pneumonia and bradyarrhythmia in patients with acute ischemic stroke.

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

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

Universal laboratory testing for SARS-CoV-2 in hyperacute stroke during the COVID-19 pandemic.

OBJECTIVE: Stroke patients are thought to be at increased risk of Coronavirus Disease 2019 (COVID-19). To evaluate yield of universal laboratory testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in acute stroke patients and its impact on hyperacute stroke care. METHODS: Between weeks 14 and 18 in 2020, a protected code stroke protocol including infection control screening and laboratory testing for SARS-CoV-2 was prospectively implemented for all code stroke patients upon arrival to the emergency department. If infection control screen was positive, patients received protective hygienic measures and laboratory test results were available within four hours from testing. In patients with negative screen, laboratory results were available no later than the next working day. Door-to-imaging times of patients treated with thrombolysis or thrombectomy were compared with those of patients treated during the preceding weeks 1 to 13 in 2020. RESULTS: During the 4-weeks study period, 116 consecutive code stroke patients underwent infection control screen and laboratory testing for SARS-CoV-2. Among 5 (4.3%) patients whose infection control screen was positive, no patient was tested positive for SARS-CoV-2. All patients with negative infection control screens had negative test results. Door-to-imaging times of patients treated with thrombolysis and/or thrombectomy were not different to those treated during the preceding weeks (12 [9-15] min versus 13 [11-17] min, p = 0.24). CONCLUSIONS: Universal laboratory testing for SARS-CoV-2 provided useful information on patients' infection status and its implementation into a protected code stroke protocol did not adversely affect hyperacute stroke care.

Decompressive Hemicraniectomy in Elderly Patients With Space-Occupying Infarction (DECAP): A Prospective Observational Study.

BACKGROUND: Decompressive hemicraniectomy improves survival rates and functional outcome in patients with space-occupying middle cerebral artery (MCA) infarction. We sought to determine clinical outcomes in elderly patients with MCA infarction treated with hemicraniectomy and to identify factors associated with functional outcome. METHODS: We performed a prospective, single-center observational study aiming to include patients aged ≥ 61 years with large MCA infarction treated with hemicraniectomy. The primary endpoint was the functional outcome according to modified Rankin Scale (mRS) score at 6 months after hemicraniectomy. Secondary endpoints included outcome measures at 12 months. A pooled analysis of individual patient data from the single-center cohort and a DESTINY 2 trial subgroup was performed to identify factors associated with functional status at 12 months. RESULTS: We included 40 MCA infarction patients who underwent hemicraniectomy between 2012 and 2017 at our university hospital (median [IQR] patient age 64 [62-67] years, National Institutes of Health Stroke Scale score 17 [16-21]). The dominant hemisphere was affected in 22/40 patients. Hemicraniectomy was performed within 31 [23-53] h of symptom onset. At 6 months after hemicraniectomy, 6/40 patients (15%) were moderately or moderately severely disabled (mRS score 3 or 4), 19 (47.5%) severely disabled (mRS score 5), and 15 (37.5%) had died. Compared to surgically treated DESTINY 2 patients, the single-center patients less likely exhibited favorable functional outcome at 6 months (mRS scores 0-4; odds ratio 0.239 [95% CI 0.082-0.696]). Case-fatality rate at 12 months was 43%. In a pooled analysis including 79 patients from DECAP and DESTINY 2, no significant associations of baseline and treatment factors with the clinical status at 12 months were observed. CONCLUSIONS: In this single-center cohort of elderly patients with space-occupying MCA infarction and decompressive hemicraniectomy, the probability for survival without severe disability was low. Lethality at 6 and 12 months was comparable to previously reported data from a randomized trial.

Validation of Multiparametric Ultrasonography Criteria with Digital Subtraction Angiography in Carotid Artery Disease: A Prospective Multicenter Study.

PURPOSE: The German Society of Ultrasound in Medicine (DEGUM) recently revised its multiparametric criteria for duplex ultrasonography (DUS) grading of internal carotid artery (ICA) disease. We determined the diagnostic accuracy of the revised DEGUM criteria for ultrasonography grading of ICA disease in a prospective multicenter study. MATERIALS AND METHODS: We evaluated consecutive patients who underwent digital subtraction angiography of the extracranial carotid arteries at four tertiary care hospitals. Blinded investigators graded ICA disease according to DEGUM-recommended ultrasonography criteria and calculated NASCET-type percent stenosis from angiography images. Endpoints included overall classification accuracy, prediction of clinically relevant disease categories and between-test agreement in the continuous range of percent stenosis. RESULTS: A total of 121 patients (median age: 69 [IQR, 16] years; 74 % men; median time between DUS and angiography: 1 day [IQR, 2]) provided 163 DUS-angiography carotid artery pairs. The classification accuracy of the DEGUM criteria to predict stenosis within 10 % increments as compared to angiography was 34.9 % (95 % CI, 28.0 - 42.6). The sensitivity of DUS for the detection of moderate (50 - 69 %) and severe (70 - 99 %) stenosis was 35 % and 81 %, with an overall accuracy of 73 % and 74 %, respectively. The specificity was 89 % and 69 %, respectively. Considering the continuous spectrum of the disease (0 - 100 %), the Bland-Altman interval limit of agreement was 51 %. CONCLUSION: At laboratories experienced with ultrasound grading of the extracranial ICA, the revised DEGUM multiparametric ultrasonography criteria do not eliminate the need for a confirmatory test for the identification of clinically relevant grades of the disease.

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

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

Case management-based post-stroke care for patients with acute stroke and TIA (SOS-Care): a prospective cohort study.

BACKGROUND: The high incidence of stroke recurrence necessitates effective post-stroke care. This study investigates the effectiveness of a case management-based post-stroke care program in patients with acute stroke and TIA. METHODS: In this prospective cohort study, patients with TIA, ischemic stroke or intracerebral hemorrhage were enrolled into a 12-month case management-based program (SOS-Care) along with conventional care. Control patients received only conventional care. The program included home and phone consultations by case managers, focusing on education, medical and social needs and guideline-based secondary prevention. The primary outcome was the composite of stroke recurrence and vascular death after 12 months. Secondary outcomes included vascular risk factor control at 12 months. RESULTS: From 11/2011 to 12/2020, 1109 patients (17.9% TIA, 77.5% ischemic stroke, 4.6% intracerebral hemorrhage) were enrolled. After 85 (7.7%) dropouts, 925 SOS-Care patients remained for comparative analysis with 99 controls. Baseline characteristics were similar, except for fewer males and less frequent history of dyslipidemia in post-stroke care. At 12 months, post-stroke care was associated with a reduction in the composite endpoint compared to controls (4.9 vs. 14.1%; HR 0.30, 95% CI 0.16-0.56, p < 0.001), with consistent results in ischemic stroke patients alone (HR 0.32, 95% CI 0.17-0.61, p < 0.001). Post-stroke care more frequently achieved treatment goals for hypertension, dyslipidemia, diabetes, BMI and adherence to secondary prevention medication (p < 0.05). CONCLUSIONS: Case management-based post-stroke care may effectively mitigate the risk of vascular events in unselected stroke patients. These findings could guide future randomized trials investigating the efficacy of case management-based models in post-stroke care.

The impact of mechanical devices for lifting and transferring of patients on low back pain and musculoskeletal injuries in health care personnel-A systematic review and meta-analysis.

OBJECTIVES: Heavy lifting in nursing is highly associated with low back pain (LBP) and musculoskeletal injuries (MSI). We aimed to evaluate the impact of mechanical devices used for patient lifting and transferring on risk of LBP and MSI of health care personnel. METHODS: We conducted a systematic review and meta-analysis. The literature search was performed during 1st and 12th September 2021 using 17 electronic databases and handsearching of bibliographies of included studies. Twenty studies were included in the qualitative synthesis and eight studies with in total 2087 participants in the meta-analysis. Dependent on the study design, risk of bias was assessed by Cochrane RoB 2.0, EPOC, and MINORS. We conducted random-effects meta-analyses assessing Hedges's g and 95% CI of MSI rate, perceived LBP, and peak compressive spinal load. We calculated prediction intervals and conducted a cost-benefit analysis (CBA). RESULTS: All outcomes showed significant, adjusted pooled effect sizes (MSI rate: g = 1.11, 95% CI 0.914-1.299; perceived LBP: g = 1.54, 95% CI -0.016-3.088; peak compressive spinal load: g = 1.04, 95% CI -0.315 to 2.391). True effect sizes in 95% of all comparable populations fell in the following prediction intervals: MSI rate = -1.07-3.28, perceived LBP = -0.522-3.594, and peak compressive spinal load = -15.49 to 17.57. CBA revealed cost-benefit ratios of 1.2 and 3.29 between cumulative total savings and investment costs of intervention. CONCLUSIONS: Prediction intervals confirmed strong true effect sizes for MSI rate and perceived LBP in 95% of all comparable populations but not for peak compressive spinal load. Mechanical lifting and transferring devices displayed a favorable cost-benefit ratio and should be considered for clinical implementation.

Intravenous thrombolysis and endovascular therapy for acute ischemic stroke in COVID-19: a systematic review and meta-analysis.

Background: The impact of COVID-19 on clinical outcomes in acute ischemic stroke patients receiving reperfusion therapy remains unclear. We therefore aimed to synthesize the available evidence to investigate the safety and short-term efficacy of reperfusion therapy in this patient population. Methods: We searched the electronic databases MEDLINE, Embase and Cochrane Library Reviews for randomized controlled trials and observational studies that investigated the use of intravenous thrombolysis, endovascular therapy, or a combination of both in acute ischemic stroke patients with laboratory-confirmed COVID-19, compared to controls. Our primary safety outcomes included any intracerebral hemorrhage (ICH), symptomatic ICH and all-cause in-hospital mortality. Short-term favorable functional outcomes were assessed at discharge and at 3 months. We calculated pooled risk ratios (RR) and 95% confidence intervals (CI) using DerSimonian and Laird random-effects model. Heterogeneity was evaluated using Cochran's Q test and I2 statistics. Results: We included 11 studies with a total of 477 COVID-19 positive and 8,092 COVID-19 negative ischemic stroke patients who underwent reperfusion therapy. COVID-19 positive patients exhibited a significantly higher risk of experiencing any ICH (RR 1.54, 95% CI 1.16-2.05, p < 0.001), while the nominally increased risk of symptomatic ICH in these patients did not reach statistical significance (RR 2.04, 95% CI 0.97-4.31; p = 0.06). COVID-19 positive stroke patients also had a significantly higher in-hospital mortality compared to COVID-19 negative stroke patients (RR 2.78, 95% CI 2.15-3.59, p < 0.001). Moreover, COVID-19 positive stroke patients were less likely to achieve a favorable functional outcome at discharge (RR 0.66, 95% CI 0.51-0.86, p < 0.001) compared to COVID-19 negative patients, but this difference was not observed at 3-month follow-up (RR 0.64, 95% CI 0.14-2.91, p = 0.56). Conclusion: COVID-19 appears to have an adverse impact on acute ischemic stroke patients who undergo reperfusion therapy, leading to an elevated risk of any ICH, higher mortality and lower likelihood of favorable functional outcome. Systematic review registration: PROSPERO, identifier CRD42022309785.

Assessment and Therapeutic Modulation of Heart Rate Variability: Potential Implications in Patients with COVID-19.

Cardiac damage has been attributed to SARS-CoV-2-related pathology contributing to increased risk of vascular events. Heart rate variability (HRV) is a parameter of functional neurocardiac integrity with low HRV constituting an independent predictor of cardiovascular mortality. Whether structural cardiac damage translates into neurocardiac dysfunction in patients infected with SARS-CoV-2 remains poorly understood. Hypothesized mechanisms of possible neurocardiac dysfunction in COVID-19 comprise direct systemic neuroinvasion of autonomic control centers, ascending virus propagation along cranial nerves and cardiac autonomic neuropathy. While the relationship between the autonomic nervous system and the cytokine cascade in general has been studied extensively, the interplay between the inflammatory response caused by SARS-CoV-2 and autonomic cardiovascular regulation remains largely unclear. We reviewed the current literature on the potential diagnostic and prognostic value of autonomic neurocardiac function assessment via analysis of HRV including time domain and spectral analysis techniques in patients with COVID-19. Furthermore, we discuss potential therapeutic targets of modulating neurocardiac function in this high-risk population including HRV biofeedback and the impact of long COVID on HRV as well as the approaches of clinical management. These topics might be of particular interest with respect to multimodal pandemic preparedness concepts.

Pathophysiology of Cardiac Injury in COVID-19 Patients with Acute Ischaemic Stroke: What Do We Know So Far?-A Review of the Current Literature.

With the onset of the COVID-19 pandemic, it became apparent that, in addition to pulmonary infection, extrapulmonary manifestations such as cardiac injury and acute cerebrovascular events are frequent in patients infected with SARS-CoV-2, worsening clinical outcome. We reviewed the current literature on the pathophysiology of cardiac injury and its association with acute ischaemic stroke. Several hypotheses on heart and brain axis pathology in the context of stroke related to COVID-19 were identified. Taken together, a combination of disease-related coagulopathy and systemic inflammation might cause endothelial damage and microvascular thrombosis, which in turn leads to structural myocardial damage. Cardiac complications of this damage such as tachyarrhythmia, myocardial infarction or cardiomyopathy, together with changes in hemodynamics and the coagulation system, may play a causal role in the increased stroke risk observed in COVID-19 patients. These hypotheses are supported by a growing body of evidence, but further research is necessary to fully understand the underlying pathophysiology and allow for the design of cardioprotective and neuroprotective strategies in this at risk population.

Optimizing Time Management for Drip-and-Ship Stroke Patients Qualifying for Endovascular Therapy-A Single-Network Study.

BACKGROUND: We sought to identify factors for delayed drip-and-ship (DS) management in stroke patients transferred from primary hospitals to our comprehensive stroke center (CSC) for endovascular therapy (EVT). METHODS: We conducted a retrospective study of all patients transferred to our CSC for EVT between 2016 and 2020. We analyzed emergency and hospital records to assess DS process times and factors predictive of delays. We dichotomized the admission period to 2016−2017 and 2018−2020 according to the main process optimization, including the introduction of a prenotification call. RESULTS: We included 869 DS patients (median age 76 years (IQR 65−82), NIHSS 16 (IQR 11−21), 278 min (IQR 243−335) from onset to EVT); 566 were transferred in 2018−2020. Admission in 2016−2017, during on-call, longer tranfer distance, and general anesthesia were factors independently associated with delayed onset to EVT time (F(5, 352) = 14.76, p < 0.000). Other factors associated with delayed DS management were: transfer mode, primary hospital type, site of large-vessel occlusion, and intravenous thrombolysis. Total transfer time was faster for distances <50 km by ambulance and for distances >71 km by helicopter. CONCLUSION: Assessment of DS processes and times throughout the patient pathway allows identification of potentially modifiable factors for improvement of the very time-critical workflow for stroke patients.

Delayed Comprehensive Stroke Unit Care Attributable to the Evolution of Infection Protection Measures across Two Consecutive Waves of the COVID-19 Pandemic.

We aimed to assess how evidence-based stroke care changed over the two waves of the COVID-19 pandemic. We analyzed acute stroke patients admitted to a tertiary care hospital in Germany during the first (2 March 2020-9 June 2020) and second (23 September 2020-31 December 2020, 100 days each) infection waves. Stroke care performance indicators were compared among waves. A 25.2% decline of acute stroke admissions was noted during the second (n = 249) compared with the first (n = 333) wave of the pandemic. Patients were more frequently tested SARS-CoV-2 positive during the second than the first wave (11 (4.4%) vs. 0; p < 0.001). There were no differences in rates of reperfusion therapies (37% vs. 36.5%; p = 1.0) or treatment process times (p > 0.05). However, stroke unit access was more frequently delayed (17 (6.8%) vs. 5 (1.5%); p = 0.001), and hospitalization until inpatient rehabilitation was longer (20 (1, 27) vs. 12 (8, 17) days; p < 0.0001) during the second compared with the first pandemic wave. Clinical severity, stroke etiology, appropriate secondary prevention medication, and discharge disposition were comparable among both waves. Infection control measures may adversely affect access to stroke unit care and extend hospitalization, while performance indicators of hyperacute stroke care seem to be untainted.

Video-Oculography-Assisted Head Impulse Test and Caloric Testing for Detecting Stroke in Acute Vertigo Patients via Modified HINTS Plus.

BACKGROUND: We assessed whether detection of stroke underlying acute vertigo using HINTS plus (head-impulse test, nystagmus type, test of skew, hearing loss) can be improved by video-oculography for automated head-impulse test (V-HIT) analysis. METHODS: We evaluated patients with acute vestibular syndrome (AVS) presenting to the emergency room using HINTS plus and V-HIT-assisted HINTS plus in a randomized sequence followed by cranial MRI and caloric testing. Image-confirmed posterior circulation stroke or vertebrobasilar TIA were the reference standards to calculate diagnostic accuracy. We repeated statistical analysis for a third protocol that was composed post hoc by replacing the head-impulse test with caloric testing in the HINTS plus protocol. RESULTS: We included 30 AVS patients (ages 55.4 ± 17.2 years, 14 females). Of these, 11 (36.7%) had posterior circulation stroke (n = 4) or TIA (n = 7). Acute V-HIT-assisted HINTS plus was feasible and displayed tendentially higher accuracy than conventional HINTS plus (sensitivity: 81.8%, 95% CI 48.2-97.7%; specificity 31.6%, 95% CI 12.6-56.6% vs. sensitivity 72.7%, 95% CI 39.0-94.0%; specificity 36.8%, 95% CI 16.3-61.6%). The new caloric-supported algorithm showed high accuracy (sensitivity 100%, 95% CI 66.4-100%; specificity 66.7%, 95% CI 41-86.7%). CONCLUSIONS: Our study provides pilot data on V-HIT-assisted HINTS plus for acute AVS assessment and indicates the diagnostic value of integrated acute caloric testing.

Sertraline for Functional Recovery After Acute Ischemic Stroke: A Prospective Observational Study.

Background: Neuroprotective and neurorestorative effects have been postulated for selective serotonin-reuptake inhibitors (SSRI). We hypothesized that sertraline, which is characterized by less severe adverse effects and more stable pharmacokinetics than classic SSRI, is associated with improved functional recovery in acute ischemic stroke patients with motor deficits. Methods: Prospective observational study of consecutive acute ischemic stroke patients who received sertraline for clinically suspected post-stroke depression (PSD) or at high risk for PSD. Eligibility comprised acute motor deficit caused by ischemic stroke (≥2 points on NIHSS motor items) and functional independence pre-stroke (mRS ≤1). Decision to initiate treatment with SSRI during hospital stay was at the discretion of the treating stroke physician. Patients not receiving sertraline served as control group. Favorable functional recovery defined as mRS ≤2 was prospectively assessed at 3 months. Multivariable logistic regression analysis was used to explore the effects of sertraline on 3-months functional recovery. Secondary outcomes were frequency of any and incident PSD (defined by BDI ≥10) at 3 months. Results: During the study period (03/2017-12/2018), 114 patients were assigned to sertraline (n = 72, 62.6%) or control group (n = 42, 37.4%). At study entry, patients in sertraline group were more severely neurologically affected than patients in the control group (NIHSS: 8 [IQR, 5-11] vs. 5 [IQR, 4-7]; p = 0.002). Also, motor NIHSS scores were more pronounced in sertraline than in control group (4 [IQR 2-7] vs. 2 [IQR 2-4], p = 0.001). After adjusting for age and baseline NIHSS, multivariable regression analysis revealed a significant association between sertraline intake and favorable functional outcome at 3 months (OR 3.10, 95% CI 1.02-9.41; p = 0.045). There was no difference between both groups regarding the frequency of any depression at 3 months (26/53 [49.1%] vs. 14/28 [50.0%] patients, p = 0.643, BDI ≥10). However, fewer incident depressions were observed in sertraline group patients compared to patients in control group (0/53 [0%] vs. 5/28 [17.9%] patients, p = 0.004). Conclusions: In this non-randomized comparison, early treatment with sertraline tended to favor functional recovery in patients with acute ischemic stroke. While exploratory in nature, this hypothesis needs further investigation in a clinical trial.

CT Angiography Manual Multiplanar Vessel Diameter Measurement vs. Semiautomated Perpendicular Area Minimal Caliber Computation of Internal Carotid Artery Stenosis.

Objective: To determine the diagnostic agreement of CT angiography (CTA) manual multiplanar reformatting (MPR) stenosis diameter measurement and semiautomated perpendicular stenosis area minimal caliber computation of extracranial internal carotid artery (ICA) stenosis. Methods: We analyzed acute cerebral ischemia CTA at our tertiary stroke center in a 12-month period. Prospective NASCET-type stenosis grading for each ICA was independently performed using (1) MPR to manually determine diameters and (2) perpendicular stenosis area with minimal caliber semiautomated computation to grade luminal constriction. Corresponding to clinically relevant NASCET strata, results were grouped into severity ranges: normal, 1-49%, 50-69%, and 70-99%, and occlusion. Results: We included 647 ICA pairs from 330 patients (median age of 74 [66-80, IQR]; 38-92 years; 58% men; median NIHSS 4 [1-9, IQR]). MPR diameter and semiautomated caliber measurements resulted in stenosis grades of 0-49% in 143 vs. 93, 50-69% in 29 vs. 27, 70-99% in 6 vs. 14, and occlusion in 34 vs. 34 ICAs (p = 0.003), respectively. We found excellent reliability between repeated manual CTA assessments of one expert reader (ICC = 0.997; 95% CI, 0.993-0.999) and assessments of two expert readers (ICC = 0.972; 95% CI, 0.936-0.988). For the semiautomated vessel analysis software, both intrarater reliability and interrater reliability were similarly strong (ICC = 0.981; 95% CI, 0.952-0.992 and ICC = 0.745; 95% CI, 0.486-0.883, respectively). However, Bland-Altman analysis revealed a mean difference of 1.6% between the methods within disease range with wide 95% limits of agreement (-16.7-19.8%). This interval even increased with exclusively considered vessel pairs of stenosis ≥1% (mean 5.3%; -24.1-34.7%) or symptomatic stenosis ≥50% (mean 0.1%; -25.7-26.0%). Conclusion: Our findings suggest that MPR-based diameter measurement and the semiautomated perpendicular area minimal caliber computation methods cannot be used interchangeably for the quantification of ICA steno-occlusive disease.

Effects of digitalized university curriculum-associated teaching on the equilibrium of autonomic neurophysiology and disposition of learners in medical school (EDUCATE-AND-LEARN): protocol for a randomized crossover study.

BACKGROUND: Homoeostasis of the autonomic nervous system (ANS) contributes to cognitive functional integrity in learners and can be greatly influenced by emotions and stress. While moderate stress can enhance learning and memory processes, long-term stress compromises learning performance in a face-to-face classroom environment. Integrative online learning and communication tools were shown to be beneficial for visualization and comprehension but their effects on the ANS are poorly understood. We aim to assess the effects of video conference-supported live lectures compared to on-site classroom teaching on autonomic functions and their association with learning performance. METHODS AND DESIGN: Fifty mentally and physically healthy medical students will be enrolled in a randomized two-period crossover study. Subjects will attend a seminar, which is held in face-to-face and simultaneously transmitted via videoconference. Subjects will be allocated in two arms in a randomized sequence determining the order in which both seminar settings will be attended. At baseline and throughout the interactive seminar subjects will undergo detailed autonomic testing comprising neurocardiac (heart rate variability), sudomotor (sympathetic skin response), neurovascular (laser Doppler flowmetry) and pupillomotor (pupillography) function. Furthermore, learning progress will be evaluated using pre- and post-tests on the seminar subject and emotions will be assessed using profile of mood state (POMS) questionnaire. STATISTICAL ANALYSIS: Carryover effects will be handled using a two-way repeated measures (mixed model). Between-group differences (baseline vs face-to-face vs videoconference) will be determined using one-way analysis of variance ANOVA followed by Student-Newman-Keul test. LIMITATIONS AND STRENGTHS: This study may elucidate complex interactions between autonomic and emotional dynamics during conventional on-site and video conference-based teaching, thus providing a basis for customized learning and teaching methods. Understanding and utilizing advanced distance learning strategies is particularly important during the current pandemic, which has been limiting on-site teaching dramatically in nearly all countries of the world.

Cerebrovascular Risk Profiles in a Saudi Arabian Cohort of Young Stroke Patients.

Background: The constantly increasing incidence of stroke in younger individuals substantiates an urgent need for research to elucidate underlying risk factors and etiologies. Heretofore, the vast majority of studies on stroke in the young have been carried out in European and North American regions. We aimed to characterize cerebrovascular risk profiles in a Saudi Arabic cohort of consecutive young stroke patients. Methods: We retrospectively analyzed data from consecutive ischemic stroke patients aged 15 to 49 years who underwent detailed cardiocerebrovascular evaluation at a tertiary stroke care center in Makkah, Saudi Arabia. Distributions of risk factors and stroke etiologies were assessed in the entire cohort and in two strata of very young (15-40 years) and young to middle-aged patients (41-49) to account for variability in suggested age cutoffs. Results: In the entire cohort [n = 63, ages 44 (34-47) median, interquartile range], dyslipidemia (71.4%) and small vessel occlusion (31.7%) displayed highest prevalence followed by diabetes (52.4%) and cardioembolism (19%). In very young patients, cardioembolism was the most prevalent etiology (27.3%). Risk profiles were similar between both age strata except for a higher prevalence of diabetes among the older cohort (31.8 vs. 63.4%, p = 0.01). Logistic regression identified diabetes as strongest predictor for association to the older strata (odds ratio = 4.2, 95% confidence interval = 1.2-14.1, p = 0.02). Conclusion: Cerebrovascular risk profiles and stroke etiologies in our cohort of young stroke patients differ from those of previous cohorts, suggesting the need for tailored prevention strategies that take into account local epidemiological data on cerebrovascular health.