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.
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.
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).
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.
ClinicalTrials.gov NCT01855035.
Summary 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.
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.
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).
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.
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.
Despite the presence of neural stem cells and ongoing neurogenesis in some regions of the adult mammalian brain, neurons are not replaced in most brain regions after injury. With the aim to unravel ...factors contributing to the failure of neurogenesis in the injured cerebral cortex, we examined the expression of cell fate determinants after acute brain injuries, such as stab wound or focal ischemia, and in a model of chronic amyloid deposition. Although none of the neurogenic factors, such as Pax6, Mash1, Ngn2, was detected in the injured parenchyma, we observed a strong up-regulation of the bHLH transcription factor Olig2, but not Olig1, upon acute and chronic injury. To examine the function of Olig2 in brain lesion, we injected retroviral vectors containing a dominant negative form of Olig2 into the lesioned cortex 2 days after a stab wound. Antagonizing Olig2 function resulted in a significant number of infected cells generating immature neurons that were not observed after injection of the control virus. These data, therefore, imply Olig2 as a repressor of neurogenesis in cells reacting to brain injury and open innovative perspectives toward evoking endogenous neuronal repair.
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—URLhttps://www.clinicaltrials.gov. Unique identifierNCT01855035.
Glial fibrillary acidic protein (GFAP) is a biomarker candidate indicative of intracerebral hemorrhage (ICH) in patients with symptoms of acute stroke. GFAP is released rapidly in the presence of ...expanding intracerebral bleeding, whereas a more gradual release occurs in ischemic stroke. In this study the diagnostic accuracy of plasma GFAP was determined in a prospective multicenter approach.
Within a 1-year recruitment period, patients suspected of having acute (symptom onset<4.5 h before admission) hemispheric stroke were prospectively included into the study in 14 stroke centers in Germany and Switzerland. A blood sample was collected at admission, and plasma GFAP was measured by use of an electrochemiluminometric immunoassay. The final diagnosis, established at hospital discharge, was classified as ICH, ischemic stroke, or stroke mimic.
The study included 205 patients (39 ICH, 163 ischemic stroke, 3 stroke mimic). GFAP concentrations were increased in patients with ICH compared with patients with ischemic stroke median (interquartile range) 1.91 μg/L (0.41-17.66) vs 0.08 μg/L (0.02-0.14), P<0.001. Diagnostic accuracy of GFAP for differentiating ICH from ischemic stroke and stroke mimic was high area under the curve 0.915 (95% CI 0.847-0.982), P<0.001. A GFAP cutoff of 0.29 μg/L provided diagnostic sensitivity of 84.2% and diagnostic specificity of 96.3% for differentiating ICH from ischemic stroke and stroke mimic.
Plasma GFAP analysis performed within 4.5 h of symptom onset can differentiate ICH and ischemic stroke. Studies are needed to evaluate a GFAP point-of-care system that may help optimize the prehospital triage and management of patients with symptoms of acute stroke.
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.
Nucleosomes, complexes of DNA and histone proteins, are released during cell death into the blood circulation. Elevated serum and plasma levels have been found in various forms of cancer, but also in ...autoimmune diseases and acute situations such as stroke, trauma, and during sepsis. Here, the clinical relevance of circulating nucleosomes for diagnosis, staging, prognosis, and therapeutic monitoring of cancer is reviewed. Several studies have shown that levels of nucleosomes are significantly higher in serum and plasma of cancer patients in comparison to healthy controls. However, because of elevations of nucleosome levels in patients with benign diseases relevant for differential diagnosis, they are not suitable for cancer diagnosis. Concerning tumor staging, nucleosome levels correlate with tumor stage and presence of metastases in gastrointestinal cancer, but not in other tumor types. Prognostic value of circulating nucleosomes is found in lung cancer in univariate analyses, but not in multivariate analyses. Circulating nucleosomes are most informative for the monitoring of cytotoxic therapy. Strongly decreasing levels are mainly found in patients with remission of disease, whereas constantly high or increasing values are associated with progressive disease during chemo‐ and radiotherapy. In addition, therapy outcome is already indicated by the nucleosomal course during the first week of chemo‐ and radiotherapy in patients with lung, pancreatic, and colorectal cancer as well as in hematologic malignancies. Despite their non‐tumor‐specificity, kinetics of nucleosomes are valuable markers for the early estimation of therapeutic efficacy and may be helpful to adapting early cancer therapy in the future.
OBJECTIVETo 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).
METHODSThis 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.
RESULTSMT was performed in 410 patients221 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.
CONCLUSIONDS 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.
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.
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).
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 (β = 0.37, p < .01), 6 months (β = 0.43, p < .01) and 12 months (β = 0.44, p < .01) post-stroke compared to baseline. HADS anxiety scores after 3 months (β = −0.22, p < .01) and 12 months (β = −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.
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-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01855035.
•HRQoL and anxiety improved significantly within the first 3 months after stroke.•Older patients and females reported reduced HRQoL and depression or anxiety.•Surprisingly, there was a small positive effect of AF on HRQoL and anxiety.•Most serious strokes are associated with reduced short-term post-stroke HRQoL.•This negative effect of stroke severity on HRQoL disappears at 12 months post stroke.
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