Telemedical stroke care significantly improves patient outcome in rural areas: Long-term analysis of the German NEVAS network.

BACKGROUND: Comprehensive stroke centers (CSC) offer state-of-the-art stroke care in metropolitan centers. However, in rural areas, sufficient stroke expertise is much scarcer. Recently, telemedical stroke networks have offered instant consultation by stroke experts, enabling immediate administration of intravenous thrombolysis (IVT) on-site and decision on thrombectomy. While these immediate decisions are made during the consult, the impact of the network structures on stroke care in spoke hospitals is still not well described. AIMS: This study was performed to determine if on-site performance in rural hospitals and patient outcome improve over time through participation and regular medical staff training within a telemedical stroke network. METHODS: In this retrospective study, we analyzed data from stroke patients treated in four regional hospitals within the telemedical Neurovascular Network of Southwest Bavaria (NEVAS) between 2014 and 2019. We only included those patients that were treated in the regional hospitals until discharge at home or to neurorehabilitation. Functional outcome (modified Rankin scale) at discharge, mortality rate and periprocedural intracranial hemorrhage served as primary outcome parameters. Door-to-imaging and door-to-needle times were secondary outcome parameters. RESULTS: In 2014-2019, 5,379 patients were treated for acute stroke with 477 receiving IVT. Most baseline characteristics were comparable over time. For all stroke patients, door-to-imaging times increased over the years, but significantly improved for potential IVT candidates and those finally treated with IVT. The percentage of patients with door-to-needle time <30 min increased from 10% to 25%. Clinical outcome at discharge improved for all stroke patients treated in the regional hospitals. Particularly for patients treated with IVT, good clinical outcome (modified Rankin scale 0-2) at discharge increased from 2014 to 2019 by 19% and mortality rates dropped from 13% to 5%. CONCLUSIONS: 24-h/7-day telemedical support and regular on-site medical staff training within a structured telemedicine stroke network such as NEVAS significantly improve on-site stroke care in rural areas, leading to a considerable benefit in clinical outcome. DATA ACCESS STATEMENT: The data that support the findings of this study are available upon reasonable request and in compliance with the local and international ethical guidelines.

KCNA2 IgG autoimmunity in neuropsychiatric diseases.

BACKGROUND: Autoantibodies against the potassium voltage-gated channel subfamily A member 2 (KCNA2) have been described in a few cases of neuropsychiatric disorders, but their diagnostic and pathophysiological role is currently unknown, imposing challenges to medical practice. DESIGN / METHODS: We retrospectively collected comprehensive clinical and paraclinical data of 35 patients with KCNA2 IgG autoantibodies detected in cell-based and tissue-based assays. Patients' sera and cerebrospinal fluid (CSF) were used for characterization of the antigen, clinical-serological correlations, and determination of IgG subclasses. RESULTS: KCNA2 autoantibody-positive patients (n = 35, median age at disease onset of 65 years, range of 16-83 years, 74 % male) mostly presented with cognitive impairment and/or epileptic seizures but also ataxia, gait disorder and personality changes. Serum autoantibodies belonged to IgG3 and IgG1 subclasses and titers ranged from 1:32 to 1:10,000. KCNA2 IgG was found in the CSF of 8/21 (38 %) patients and in the serum of 4/96 (4.2 %) healthy blood donors. KCNA2 autoantibodies bound to characteristic anatomical areas in the cerebellum and hippocampus of mammalian brain and juxtaparanodal regions of peripheral nerves but reacted exclusively with intracellular epitopes. A subset of four KCNA2 autoantibody-positive patients responded markedly to immunotherapy alongside with conversion to seronegativity, in particular those presenting an autoimmune encephalitis phenotype and receiving early immunotherapy. An available brain biopsy showed strong immune cell invasion. KCNA2 autoantibodies occurred in less than 10 % in association with an underlying tumor. CONCLUSION: Our data suggest that KCNA2 autoimmunity is clinically heterogeneous. Future studies should determine whether KCNA2 autoantibodies are directly pathogenic or develop secondarily. Early immunotherapy should be considered, in particular if autoantibodies occur in CSF or if clinical or diagnostic findings suggest ongoing inflammation. Suspicious clinical phenotypes include autoimmune encephalitis, atypical dementia, new-onset epilepsy and unexplained epileptic seizures.

Intensive heart rhythm monitoring to decrease ischemic stroke and systemic embolism-the Find-AF 2 study-rationale and design.

BACKGROUND: Atrial fibrillation (AF) is one of the most frequent causes of stroke. Several randomized trials have shown that prolonged monitoring increases the detection of AF, but the effect on reducing recurrent cardioembolism, ie, ischemic stroke and systemic embolism, remains unknown. We aim to evaluate whether a risk-adapted, intensified heart rhythm monitoring with consequent guideline conform treatment, which implies initiation of oral anticoagulation (OAC), leads to a reduction of recurrent cardioembolism. METHODS: Find-AF 2 is a randomized, controlled, open-label parallel multicenter trial with blinded endpoint assessment. 5,200 patients ≥ 60 years of age with symptomatic ischemic stroke within the last 30 days and without known AF will be included at 52 study centers with a specialized stroke unit in Germany. Patients without AF in an additional 24-hour Holter ECG after the qualifying event will be randomized in a 1:1 fashion to either enhanced, prolonged and intensified ECG-monitoring (intervention arm) or standard of care monitoring (control arm). In the intervention arm, patients with a high risk of underlying AF will receive continuous rhythm monitoring using an implantable cardiac monitor (ICM) whereas those without high risk of underlying AF will receive repeated 7-day Holter ECGs. The duration of rhythm monitoring within the control arm is up to the discretion of the participating centers and is allowed for up to 7 days. Patients will be followed for at least 24 months. The primary efficacy endpoint is the time until recurrent ischemic stroke or systemic embolism occur. CONCLUSIONS: The Find-AF 2 trial aims to demonstrate that enhanced, prolonged and intensified rhythm monitoring results in a more effective prevention of recurrent ischemic stroke and systemic embolism compared to usual care.

The structured ambulatory post-stroke care program for outpatient aftercare in patients with ischaemic stroke in Germany (SANO): an open-label, cluster-randomised controlled trial.

BACKGROUND: Patients with ischaemic stroke are at risk of recurrent stroke. In this study, we aimed to compare the effect of a structured ambulatory post-stroke care programme versus usual care on recurrent vascular events and death and control of cardiovascular risk factors. METHODS: We did a prospective, open-label, cluster-randomised controlled trial (SANO) at stroke centres in regions of Germany. A cluster was defined as a region in which acute stroke care is provided by a participating stroke centre. Patients were eligible for participation if they were aged 18 years or older, had no severe disabilities before the index stroke (modified Rankin scale 0-1), had at least one modifiable cardiovascular risk factor, and presented within 14 days of symptom onset of their first ischaemic stroke. The participating regions were randomly assigned (1:1) to the intervention and control group (usual care) by the statistician using block randomisation (block sizes of six), stratified by rural and urban regions. In intervention regions, a cross-sectoral multidisciplinary network was established to provide a 1-year organisational and patient-centred intervention. Due to the type of intervention, masking of participants and study physicians was not possible. Endpoint adjudication was performed by an independent endpoint adjudication committee who were masked to cluster allocation. The primary endpoint was a composite of recurrent stroke, myocardial infarction, and all-cause death within 12 months after baseline assessment, assessed in the modified intention-to-treat (mITT) population, which included all patients who did not withdraw consent and completed the primary endpoint assessment at 12 months. This study was registered with the German Clinical Trials Register, DRKS00015322. FINDINGS: Between Jan 1, 2019 and Dec 22, 2020, 36 clusters were assessed for eligibility, of which 30 were randomly assigned to the intervention group (n=15 clusters) or control group (n=15 clusters). No clusters dropped out of the study. 1203 (86%) of 1396 enrolled patients in the intervention group and 1283 (92%) of 1395 enrolled patients in the control group were included in the mITT population. The primary endpoint was confirmed in 64 (5·3%) of 1203 patients in the intervention group and 80 (6·2%) of 1283 patients in the control group (unadjusted odds ratio [OR] 0·80 [95% CI 0·49-1·30]; adjusted OR [aOR] 0·95 [95% CI 0·54-1·67]). All-cause deaths occurred in 31 (2·4%) of 1203 patients in the intervention group and 12 (1·0%) of 1283 patients in the control group. The incidence of serious adverse events was higher in the intervention group (266 [23·1%] of 1151) than the control group (106 [9·2%] of 1152). Falls (134 [11·4%] of 1203 patients in the intervention group; 39 [3·3%] of 1152 patients in the control group), hypertensive crisis (55 [4·7%]; 34 [2·8%]), and diagnosis of depression (51 [4·3%]; 13 [1·1%]) were the most frequent adverse events in both groups. No differences were identified in the rate of readmission to hospital between groups. INTERPRETATION: No differences were identified between patients with ischaemic stroke in the intervention group and control group with regard to the incidence of vascular events 1 year after baseline assessment, despite positive effects with regard to the control of some cardiovascular risk factors. Longer-term effects and other potentially favourable effects on stroke-related sequelae and quality of life require further evaluation. FUNDING: Innovation Fund of the Federal Joint Committee.

Levels and dynamics of estimated glomerular filtration rate and recurrent vascular events and death in patients with minor stroke or transient ischemic attack.

BACKGROUND AND PURPOSE: Impaired kidney function is associated with an increased risk of vascular events in acute stroke patients, when assessed by single measurements of estimated glomerular filtration rate (eGFR). It is unknown whether repeated measurements provide additional information for risk prediction. METHODS: The MonDAFIS (Systematic Monitoring for Detection of Atrial Fibrillation in Patients with Acute Ischemic Stroke) study randomly assigned 3465 acute ischemic stroke patients to either standard procedures or an additive Holter electrocardiogram. Baseline eGFR (CKD-EPI formula) were dichotomized into values of < versus ≥60 ml/min/1.73 m2 . eGFR dynamics were classified based on two in-hospital values as "stable normal" (≥60 ml/min/1.73 m2 ), "increasing" (by at least 15% from baseline, second value ≥ 60 ml/min/1.73 m2 ), "decreasing" (by at least 15% from baseline of ≥60 ml/min/1.73 m2 ), and "stable decreased" (<60 ml/min/1.73 m2 ). The composite endpoint (stroke, major bleeding, myocardial infarction, all-cause death) was assessed after 24 months. We estimated hazard ratios in confounder-adjusted models. RESULTS: Estimated glomerular filtration rate at baseline was available in 2947 and a second value in 1623 patients. After adjusting for age, stroke severity, cardiovascular risk factors, and randomization, eGFR < 60 ml/min/1.73 m2 at baseline (hazard ratio [HR] = 2.2, 95% confidence interval [CI] = 1.40-3.54) as well as decreasing (HR = 1.79, 95% CI = 1.07-2.99) and stable decreased eGFR (HR = 1.64, 95% CI = 1.20-2.24) were independently associated with the composite endpoint. In addition, eGFR < 60 ml/min/1.732 at baseline (HR = 3.02, 95% CI = 1.51-6.10) and decreasing eGFR were associated with all-cause death (HR = 3.12, 95% CI = 1.63-5.98). CONCLUSIONS: In addition to patients with low eGFR levels at baseline, also those with decreasing eGFR have increased risk for vascular events and death; hence, repeated estimates of eGFR might add relevant information to risk prediction.

Association of Intraventricular Fibrinolysis With Clinical Outcomes in Intracerebral Hemorrhage: An Individual Participant Data Meta-Analysis.

BACKGROUND: In patients with intracerebral hemorrhage (ICH), the presence of intraventricular hemorrhage constitutes a promising therapeutic target. Intraventricular fibrinolysis (IVF) reduces mortality, yet impact on functional disability remains unclear. Thus, we aimed to determine the influence of IVF on functional outcomes. METHODS: This individual participant data meta-analysis pooled 1501 patients from 2 randomized trials and 7 observational studies enrolled during 2004 to 2015. We compared IVF versus standard of care (including placebo) in patients treated with external ventricular drainage due to acute hydrocephalus caused by ICH with intraventricular hemorrhage. The primary outcome was functional disability evaluated by the modified Rankin Scale (mRS; range: 0-6, lower scores indicating less disability) at 6 months, dichotomized into mRS score: 0 to 3 versus mRS: 4 to 6. Secondary outcomes included ordinal-shift analysis, all-cause mortality, and intracranial adverse events. Confounding and bias were adjusted by random effects and doubly robust models to calculate odds ratios and absolute treatment effects (ATE). RESULTS: Comparing treatment of 596 with IVF to 905 with standard of care resulted in an ATE to achieve the primary outcome of 9.3% (95% CI, 4.4-14.1). IVF treatment showed a significant shift towards improved outcome across the entire range of mRS estimates, common odds ratio, 1.75 (95% CI, 1.39-2.17), reduced mortality, odds ratio, 0.47 (95% CI, 0.35-0.64), without increased adverse events, absolute difference, 1.0% (95% CI, -2.7 to 4.8). Exploratory analyses provided that early IVF treatment (≤48 hours) after symptom onset was associated with an ATE, 15.2% (95% CI, 8.6-21.8) to achieve the primary outcome. CONCLUSIONS: As compared to standard of care, the administration of IVF in patients with acute hydrocephalus caused by intracerebral and intraventricular hemorrhage was significantly associated with improved functional outcome at 6 months. The treatment effect was linked to an early time window <48 hours, specifying a target population for future trials.

Long-Term Follow-up of Enhanced Holter-Electrocardiography Monitoring in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Prolonged electrocardiography (ECG)-monitoring in stroke patients improves the detection of paroxysmal atrial fibrillation (pAF). However, most randomized studies only had short follow-up. We aimed to provide 3-year follow-up data for AF detection and stroke recurrence risk. METHODS: We randomized 402 patients aged ≥60 years with acute ischemic strokes without AF to either enhanced and prolonged monitoring (EPM; 3×10-day Holter-ECG-monitoring) or standard-of-care (≥24 hours ECG-monitoring). The endpoint of the current analysis was AF within 36 months analyzed by intention to treat. Long-term follow-up was performed for 36 months. RESULTS: Two hundred and seventy-four patients (80%) participated in the extended follow-up (median duration of follow-up was 36 months [interquartile range, 12 to 36]). During the first 6 months, more AF was documented in the EPM arm compared to the control arm (13.5% vs. 5.1%; 95% confidence interval, 2.9% to 14.4%; P=0.004). During months 6 to 36, AF was less detected in the EPM intervention arm than in the control arm (2.0% vs. 7.3%; 95% confidence interval, 0.7% to 9.9%; P=0.028). Overall, the detection rate of AF within 36 months was numerically higher within the EPM group (15.0% vs. 11.1%, P=0.30). Numerically less patients in the EPM arm had recurrent ischemic strokes (5.5% vs. 9.1%, P=0.18), transient ischemic attacks (3.0% vs. 4.5%, P=0.44) or died (4.5% vs. 6.6%, P=0.37). CONCLUSIONS: Enhanced and prolonged ECG monitoring increased AF detection during the first six months, but there was significantly more clinical AF during months 6 to 36 observed in the usual-care arm. This suggests that EPM leads to an earlier detection of clinically relevant AF.

Trial design and pilot phase results of a cluster-randomised intervention trial to improve stroke care after hospital discharge - The structured ambulatory post-stroke care program (SANO).

INTRODUCTION: Previous studies showed insufficient control of cardiovascular risk factors (CVRF) and high stroke recurrence rates among ischemic stroke patients in Germany. Currently, no structured secondary prevention program exists in clinical routine. We present the trial design and pilot phase results of a complex intervention to improve stroke care after hospital discharge in Germany. PATIENTS AND METHODS: SANO is a cluster-randomized trial with 30 participating regions across Germany aiming to enrol 2,790 patients (drks.de, DRKS00015322). Study intervention combines both structural and patient-centred elements. Study development was based on the Medical Research Council framework for complex interventions. In 15 intervention regions, a cross-sectoral multidisciplinary network is established to enhance CVRF control as well as detection and treatment of post-stroke complications. Recommendations on CVRF are based on high-quality secondary prevention guidelines. Study physicians use motivational interviewing and agree with patients on therapeutic targets. While hospitalised, patients also receive dietary counselling and a health-passport to track their progress. During regular visits, CVRF management and potential complications are monitored. The intervention is compared to 15 regions providing usual care. The primary endpoint is the combination of recurrent stroke, myocardial infarction and death assessed 12 months after enrolment and adjudicated in a blinded manner. RESULTS: Eighteen patients were enrolled in a pilot phase that demonstrated feasibility of patient recruitment and study procedures. CONCLUSION: SANO is investigating a program to reduce outcome events after ischemic stroke by implementing a complex intervention. If successful, the program may be implemented in routine care on national level in Germany.

Health-related quality of life, anxiety and depression up to 12 months post-stroke: Influence of sex, age, stroke severity and atrial fibrillation - A longitudinal subanalysis of the Find-AFRANDOMISED trial.

BACKGROUND: Stroke can negatively impact the health-related quality of life (HRQoL). Anxiety or depression after stroke have been associated with poorer HRQoL, higher mortality and greater dependence in activities of daily living. We aimed to analyze HRQoL, anxiety and depressive symptoms in patients with and without atrial fibrillation (AF) up to 12 months post-stroke. METHODS: Find-AFRANDOMISED was a prospective, randomized multicenter study, which included 398 patients ≥60 years with acute cerebral ischemia. HRQoL data were collected using the 3-level EuroQol-5D (EQ-5D-3L) and Stroke Impact Scale (SIS-16). Anxiety and depressive symptoms were measured using the Hospital Anxiety and Depression Scale (HADS). The severity of stroke was measured using the modified Rankin Scale (mRS). RESULTS: In this study (mean age 72.7 ± 7.5 years, 40.2% females), there was a significant improvement in HRQoL using EQ-5D-3L after 3 months (ß = 0.37, p < .01), 6 months (ß = 0.43, p < .01) and 12 months (ß = 0.44, p < .01) post-stroke compared to baseline. HADS anxiety scores after 3 months (ß = -0.22, p < .01) and 12 months (ß = -0.28, p < .01) were significantly reduced. Older patients reported reduced HRQoL and more depressive symptoms. Females indicated lower HRQoL and more anxiety. mRS score at baseline was an independent predictor for HRQoL. There was a significant but small effect of AF on EQ-5D-3L and on HADS anxiety. CONCLUSIONS: Patients showed significant improvement in HRQoL and reduced anxiety after 3 and 12 months after stroke. We could demonstrate that the severity of stroke as well as sex and age impact long-term post-stroke HRQoL. CLINICAL TRIAL REGISTRATION: Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01855035.

Inter-hospital transfer for mechanical thrombectomy within the supraregional stroke network NEVAS.

BACKGROUND: Telemedicine stroke networks are mandatory to provide inter-hospital transfer for mechanical thrombectomy (MT). However, studies on patient selection in daily practice are sparse. METHODS: Here, we analyzed consecutive patients from 01/2014 to 12/2018 within the supraregional stroke network "Neurovascular Network of Southwest Bavaria" (NEVAS) in terms of diagnoses after consultation, inter-hospital transfer and predictors for performing MT. Degree of disability was rated by the modified Rankin Scale (mRS), good outcome was defined as mRS ≤ 2. Successful reperfusion was assumed when the modified thrombolysis in cerebral infarction (mTICI) was 2b-3. RESULTS: Of 5722 telemedicine consultations, in 14.1% inter-hospital transfer was performed, mostly because of large vessel occlusion (LVO) stroke. A total of n = 350 patients with LVO were shipped via NEVAS to our center for MT. While n = 52 recanalized spontaneously, MT-treatment was performed in n = 178 patients. MT-treated patients had more severe strokes according to the median National institute of health stroke scale (NIHSS) (16 vs. 13, p < 0.001), were more often treated with intravenous thrombolysis (64.5% vs. 51.7%, p = 0.026) and arrived significantly earlier in our center (184.5 versus 228.0 min, p < 0.001). Good outcome (27.5% vs. 30.8%, p = 0.35) and mortality (32.6% versus 23.5%, p = 0.79) were comparable in MT-treated versus no-MT-treated patients. In patients with middle cerebral artery occlusion in the M1 segment or carotid artery occlusion good outcome was twice as often in the MT-group (21.8% vs. 12.8%, p = 0.184). Independent predictors for performing MT were higher NIHSS (OR 1.096), higher ASPECTS (OR 1.28), and earlier time window (OR 0.99). CONCLUSION: Within a telemedicine network stroke care can successfully be organized as only a minority of patients has to be transferred. Our data provide clinical evidence that all MT-eligible patients should be shipped with the fastest transportation modality as possible.

Emergency carotid artery revascularization using Casper-RX stent: A single-center experience.

BACKGROUND: Casper-RX (MicroVention, Aliso Viejo, California, USA) is a dual-layer closed cell stent recently introduced as a carotid artery revascularization device. Although its effectiveness and safety has been proved in elective cases, there are contradictive results regarding its patency in emergency settings. The purpose of the study is to present our single-center experience with the Casper-RX stent in the emergency interventions. PATIENTS AND METHODS: Consecutive patients who underwent emergency carotid artery stenting using Casper-RX system with or without additional intracranial thrombectomy between August 2016 and June 2019 at our institution were included. Primary end point was the short-term patency of the carotid stents evaluated before hospital discharge by use of Doppler ultrasonography. RESULTS: Twenty-nine procedures performed on 28 patients were included in the study. All stents were patent on final angiograms. Acute stent occlusion was observed only in one case (3.4%) with a spontaneous cervical internal carotid artery dissection the day after the procedure. In 26 (89.6%) cases, an additional intracranial thrombectomy was performed with a successful recanalization rate of 96.1%. Seven adverse events occurred peri-/post-procedural: two cases (6.9%) with iatrogenic dissection of distal cervical internal carotid artery during intracranial thrombectomy, two parenchymal hematoma type 2 (6.8%), and three patients (10.3%) developed massive infarction. CONCLUSION: This study supports the safety and efficacy of the Casper-RX stent in emergency endovascular carotid artery revascularization procedures.

Drip and ship for mechanical thrombectomy within the Neurovascular Network of Southwest Bavaria.

OBJECTIVE: To determine feasibility and safety of stroke care organization within our Neurovascular Network of Southwest Bavaria (NEVAS) in a rural area with distances of up to 100 kilometers, we compared patients who underwent mechanical thrombectomy (MT) in large vessel occlusion admitted directly to our center (direct to center [DTC]) to patients who were transferred for MT via NEVAS (drip and ship [DS]). METHODS: This is a retrospective analysis of prospectively collected data of all MT patients between January 2015 and May 2018. Successful recanalization was defined as a thrombolysis in cerebral infarction score of 2b-3. Symptomatic intracerebral hemorrhage (sICH) was defined according to European Cooperative Acute Stroke Study 3. Modified Rankin Scale (mRS) score of 0-2 at 3 months indicated good outcome. RESULTS: MT was performed in 410 patients: 221 DTC and 189 DS. Median NIH Stroke Scale (NIHSS) score was 16 and premorbid mRS score was 0. Thrombolysis was applied in 62.2% with the same time from symptom onset in both groups (94.5 vs 95 minutes). Successful recanalization (79.3% vs 77.8%) and NIHSS score reduction from admission to discharge (16-7 vs 17-6) were comparable. Time delay from onset to revascularization was 96 minutes in DS (212 vs 308 minutes, p = 0.001). At follow-up, DTC patients had a trend to better outcome (33.5% vs 24.3%, p = 0.056). Neither sICH (6.3% vs 5.9%, p = 0.840) nor mortality (31.2% vs 34.4%, p = 0.387) differed between the groups. CONCLUSION: DS patients benefit from MT without relevant safety concerns, but with a trend to unfavorable outcome compared to DTC patients. These results suggest that DS is suitable to provide MT in rural areas where DTC is not possible.

Brain Natriuretic Peptide and Discovery of Atrial Fibrillation After Stroke: A Subanalysis of the Find-AFRANDOMISED Trial.

Background and Purpose- Diagnosing paroxysmal atrial fibrillation (pAF) can be challenging after acute ischemic stroke. Enhanced and prolonged Holter-ECG monitoring (EPM) improves the detection rate but is not feasible for all patients. We hypothesized that brain natriuretic peptide (BNP) may help to identify patients with stroke at high risk for pAF to select patients for EPM more effectively. Methods- Patients with acute cerebral ischemia ≥60 years presenting in sinus rhythm and without history of AF were included into a prospective, randomized multicenter study to receive either EPM (3× 10-day Holter-ECG) or usual stroke care diagnostic work-up. BNP plasma levels were measured on randomization and 3 months thereafter. Levels were compared between patients with and without pAF detected by means of EPM or usual care. Furthermore, the number needed to screen for EPM depending on BNP cut offs was calculated. Results- A total of 398 patients were analyzed. In 373 patients (93.7%), BNP was measured at baseline and in 275 patients (69.1%) after 3 months. pAF was found in 27 patients by means of EPM and in 9 patients by means of usual care (P=0.002). Median BNP was higher in patients with pAF as compared to patients without AF in both study arms at baseline (57.8 versus 28.3 pg/mL in the EPM arm, P=0.0003; 46.2 versus 27.7 pg/mL, P=0.28 in the control arm) and after 3 months (74.9 versus 31.3 pg/mL, P=0.012 in the EPM arm, 99.3 versus 26.3 pg/mL, P=0.02 in the control arm). Applying a cut off of 100 pg/mL, the number needed to screen was reduced from 18 by usual care to 3 by EPM. Conclusions- BNP measured early after ischemic stroke identifies a subgroup of patients with stroke at increased risk for AF, in whom EPM is particularly efficacious. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT01855035.

Functional Outcome Following Stroke Thrombectomy in Clinical Practice.

Background and Purpose- Endovascular treatment for large vessel occlusion in ischemic stroke has proven to be effective in large clinical trials. We aimed to provide real-world estimates of endovascular treatment reperfusion rates and functional outcome on a countrywide scale. Methods- Two thousand seven hundred ninety-four patients with large vessel occlusion were included into an investigator-initiated, industry-independent, prospective registry in 25 sites in Germany between June 2015 and April 2018. The primary outcome was the score on the modified Rankin Scale ranging from zero (no symptoms) to 6 (death) at 3 months. Secondary analyses included the prediction of a good outcome (modified Rankin Scale, 0-2). Dichotomized analyses of predictors were performed using logistic regression adjusted for potential confounders. Results- Median age was 75 years (interquartile range, 64-82); median National Institutes of Health Stroke Scale score was 15 (interquartile range, 10-19). Vessel occlusion was in the anterior circulation in 2265 patients (88%) and in the posterior circulation in 303 patients (12%). Intravenous alteplase before endovascular treatment was given in 1457 patients (56%). Successful reperfusion was achieved in 2143 subjects (83%). At 3 months, 854 patients (37%) showed a good outcome; mortality was 29%. There was no difference between anterior and posterior circulation occlusions (P=0.27). Significant predictors for a good outcome were younger age (odds ratio [OR], 1.06; 95% CI, 1.05-1.07), no interhospital transfer (OR, 1.39; 95% CI, 1.03-1.88), lower stroke severity (OR, 1.10; 95% CI, 1.08-1.13), smaller infarct size (OR, 1.26; 95% CI, 1.15-1.39), alteplase use (OR, 1.49; 95% CI, 1.08-2.06), and reperfusion success (OR, 1.69; 95% CI, 1.45-1.96). Conclusions- High rates of favorable outcome can be achieved on a countrywide scale by endovascular treatment. Mortality appears to be greater in the daily routine than otherwise reported by authors of large randomized trials. There were no outcome differences between the anterior and posterior circulation. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT03356392.

Economic evaluation of prolonged and enhanced ECG Holter monitoring in acute ischemic stroke patients.

Objective: Atrial fibrillation (AF) is a major cause for recurrent stroke, has severe impact on a patient's health and imposes a high economic burden for society. Current guidelines recommend 24 h ECG monitoring (standard-of-care, SoC) to detect AF after stroke to reduce the risk of future events. However, paroxysmal AF (PAF) is difficult to detect within this period as it occurs infrequently and unpredictably. In a randomized controlled trial (Find-AFRANDOMISED), prolonged and enhanced Holter ECG monitoring (EPM) revealed a significantly higher detection rate of AF compared to SoC, although its cost-effectiveness has not yet been investigated. Methods: Based on the data of FIND-AFRANDOMISED, an economic evaluation was conducted. One group received EPM for 10 days after the event, and at 3 and 6 months; the other group received SoC. Healthcare resource use and quality of life (QoL) data were measured at baseline, and after 6 and 12 months. Incremental costs and quality-adjusted life years (QALYs) between both groups were compared. Non-parametric bootstrapping and one-way-sensitivity analyses were performed. Results: A total of 281 patients with healthcare resource use and QoL data for all measurement points were considered in the economic evaluation (complete case analysis, CCA). The CCA yielded nonsignificant 315€ lower mean costs and 0.0013 less QALYs for patients receiving EPM with no statistically significant differences in any cost categories. Sensitivity analyses revealed robust results. Bootstrapping the results indicated moderate probability of cost-effectiveness. Conclusions: EPM yielded reduced not significantly different costs without affecting QoL and may be a useful strategy to detect PAF in acute ischemic stroke patients in time.

The cardiac diagnostic work-up in stroke patients-A subanalysis of the Find-AFRANDOMISED trial.

BACKGROUND: The cardiac diagnostic workup of stroke patients, especially the value of echocardiography and enhanced and prolonged Holter-ECG monitoring, is still a matter of debate. We aimed to analyse the impact of pathologies detected by echocardiography and ECG monitoring on therapeutic decisions and prognosis. METHODS: Find-AFRANDOMISED was a prospective multicenter study which randomised 398 acute ischemic stroke patients ≥ 60 years to enhanced and prolonged Holter-ECG monitoring or usual stroke unit care. This substudy compared therapeutic consequences of echocardiography and routine Holter-ECG or enhanced and prolonged Holter-ECG monitoring, respectively, and prognosis of patients with or without pathologic findings in echocardiography or Holter-ECG monitoring. RESULTS: 50.3% received enhanced and prolonged Holter-ECG monitoring and 49.7% routine ECG monitoring. 82.9% underwent transthoracic echocardiography (TTE), 38.9% transesophageal echocardiography (TEE) and 25.6% both procedures. 14/89 TEE pathologies and 1/90 TTE pathology led to a change in therapy, resulting in a number needed to change decision (NNCD) of 12 and 330 (p < 0.001), respectively. In comparison, enhanced and prolonged Holter-ECG monitoring found atrial fibrillation (AF) in 27 of 200 patients, and routine ECG monitoring in twelve of 198 patients, leading to therapeutic changes in all patients (NNCD 8 and 17, respectively, p < 0.001). CONCLUSIONS: Most changes in therapeutic decisions were triggered by enhanced and prolonged Holter-ECG monitoring, which should therefore play a more prominent role in future guidelines. Echocardiography identifies a patient group at high cardiovascular risk, but rarely result in therapeutic changes. Whether this patient group requires further cardiovascular workup remains unknown. This should be further investigated by interdisciplinary neurocardiologic teams and in appropriate future trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT01855035.

Position paper: ability to drive in cerebrovascular diseases.

The regulations for fitness to drive after a cerebrovascular accident in the German Driving License Regulations (FeV) and the German Evaluation Guidelines for Driving Ability (BGL). are not up to date with the current medical knowledge and not consistent with regulations regarding cardiovascular diseases. This position paper presented by six medical and neuropsychological societies in Germany provides a guideline for the assessment of driving ability after diagnosis of a cerebrovascular disease and addresses three major questions: If there is a functional limitation, how can it be compensated for? What is the risk of sudden loss of control while driving in the future? Are there behavioral or personality changes or cognitive deficiencies interfering with safety while driving? Recommendations for the assessment of driving ability in different cerebrovascular diseases are presented. This article is a translation of the position paper published in Nervenarzt: Marx, P., Hamann, G.F., Busse, O. et al. Nervenarzt 90(4): 388-398.

Holter-electrocardiogram-monitoring in patients with acute ischaemic stroke (Find-AFRANDOMISED): an open-label randomised controlled trial.

BACKGROUND: Atrial fibrillation is a major risk factor for recurrent ischaemic stroke, but often remains undiagnosed in patients who have had an acute ischaemic stroke. Enhanced and prolonged Holter-electrocardiogram-monitoring might increase detection of atrial fibrillation. We therefore investigated whether enhanced and prolonged rhythm monitoring was better for detection of atrial fibrillation than standard care procedures in patients with acute ischaemic stroke. METHODS: Find-AFrandomised is an open-label randomised study done at four centres in Germany. We recruited patients with acute ischaemic stroke (symptoms for 7 days or less) aged 60 years or older presenting with sinus rhythm and without history of atrial fibrillation. Patients were included irrespective of the suspected cause of stroke, unless they had a severe ipsilateral carotid or intracranial artery stenosis, which were the exclusion criteria. We used a computer-generated allocation sequence to randomly assign patients in a 1:1 ratio with permuted block sizes of 2, 4, 6, and 8, stratified by centre, to enhanced and prolonged monitoring (ie, 10-day Holter-electrocardiogram [ECG]-monitoring at baseline, and at 3 months and 6 months of follow-up) or standard care procedures (ie, at least 24 h of rhythm monitoring). Participants and study physicians were not masked to group assignment, but the expert committees that adjudicated endpoints were. The primary endpoint was the occurrence of atrial fibrillation or atrial flutter (30 sec or longer) within 6 months after randomisation and before stroke recurrence. Because Holter ECG is a widely used procedure and not known to harm patients, we chose not to assess safety in detail. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01855035. FINDINGS: Between May 8, 2013, and Aug 31, 2014, we recruited 398 patients. 200 patients were randomly assigned to the enhanced and prolonged monitoring group and 198 to the standard care group. After 6 months, we detected atrial fibrillation in 14% of 200 patients in the enhanced and prolonged monitoring group (27 patients) versus 5% in the control group (nine of 198 patients, absolute difference 9·0%; 95% CI 3·4-14·5, p=0·002; number needed to screen 11). INTERPRETATION: Enhanced and prolonged monitoring initiated early in patients with acute ischaemic stroke aged 60 years or older was better than standard care for the detection of atrial fibrillation. These findings support the consideration of all patients aged 60 years or older with stroke for prolonged monitoring if the detection of atrial fibrillation would result in a change in medical management (eg, initiation of anticoagulation). FUNDING: Boehringer Ingelheim.

Glial Fibrillary Acidic Protein Serum Levels Distinguish between Intracerebral Hemorrhage and Cerebral Ischemia in the Early Phase of Stroke.

BACKGROUND: Recent studies have suggested that glial fibrillary acidic protein (GFAP) serum concentrations distinguish between intracerebral hemorrhage (ICH) and ischemic stroke (IS) shortly after symptom onset. In this prospective multicenter trial we validated GFAP in an independent patient cohort and assessed the quantitative relationship between GFAP release, bleeding size, and localization. METHODS: We included patients with a persistent neurological deficit (NIH Stroke Scale ≥4) suggestive of stroke within 6 h of symptom onset. Blood samples were drawn at hospital admission. GFAP serum concentrations were measured using an electrochemiluminometric immunoassay. Primary endpoint was the final diagnosis established at hospital discharge (ICH, IS, or stroke mimic). RESULTS: 202 patients were included (45 with ICH, 146 with IS, 11 stroke mimics). GFAP concentrations were significantly higher in ICH than in IS patients [median (interquartile range) 0.16 µg/L (0.04-3.27) vs 0.01 µg/L (0.01-0.01), P <0.001]. A GFAP cutoff of 0.03 µg/L provided a sensitivity of 77.8% and a specificity of 94.2% in distinguishing ICH from IS and stroke mimics [ROC analysis area under the curve 0.872 (95% CI, 0.802-0.942), P <0.001]. GFAP serum concentrations were positively correlated with ICH volume. Lobar ICH volumes were larger and thus associated with higher GFAP concentrations as compared to deep ICH. CONCLUSIONS: Serum GFAP was confirmed to be a biomarker indicating ICH in patients presenting with acute stroke symptoms. Very small ICH may be missed owing to less tissue destruction.

Chronic Cervicogenic Tinnitus Rapidly Resolved by Intermittent Use of Cervical Collar.

INTRODUCTION: Cervicogenic tinnitus is not a generally accepted pathogenetic subtype, which might be subsumed under the concept of somatosensory tinnitus. After the personal experience of therapy-resistant tinnitus in context with a cervical pain syndrome (CPS) and successful add-on treatment with cervical collar (CC), the idea was pursued in several individual treatments in patients. PATIENTS AND METHODS: Reporting one particular case with chronic tinnitus, considered untreatable, that rapidly improved with exclusive treatment by CC use. Thereafter, tinnitus was experimentally replicated by head inclination, the respective neck-head angles, and cerebral blood flow was measured. RESULTS: Chronic subjective tinnitus of a 20 years duration completely disappeared within 4 weeks with an intermittent short time application of CC. Thereafter, tinnitus was deliberately again induced by head inclination, set on with anterior tilt of 14°, reaching maximum strength by 23°. Tinnitus stopped with return to neutral head position. Blood flow in the vertebral arteries on both sides was unchanged during head inclination with prevalent tinnitus; however, blood flow was physiologically reduced with head rotation though not accompanied by tinnitus. DISCUSSION: In a single case of chronic tinnitus, we found that treatment with CC rapidly led to full remission. Blood flow reduction in vertebral arteries was unrelated to tinnitus. However, tinnitus could be resumed by constrained head postures. Experimental tinnitus replication (by inclination) points to an underscored role of upper posterior cervical muscle groups, matching with animal experiments, also in concert with other triggers including psychological factors.