The effect of robot-assisted versus standard training on motor function following subacute rehabilitation after ischemic stroke - protocol for a randomised controlled trial nested in a prospective cohort (RoboRehab).

BACKGROUND: Body weight unloaded treadmill training has shown limited efficacy in further improving functional capacity after subacute rehabilitation of ischemic stroke patients. Dynamic robot assisted bodyweight unloading is a novel technology that may provide superior training stimuli and continued functional improvements in individuals with residual impairments in the chronic phase after the ischemic insult. The aim of the present study is to investigate the effect of dynamic robot-assisted versus standard training, initiated 6 months post-stroke, on motor function, physical function, fatigue, and quality of life in stroke-affected individuals still suffering from moderate-to-severe disabilities after subacute rehabilitation. METHODS: Stroke-affected individuals with moderate to severe disabilities will be recruited into a prospective cohort with measurements at 3-, 6-, 12- and 18-months post-stroke. A randomised controlled trial (RCT) will be nested in the prospective cohort with measurements pre-intervention (Pre), post-intervention (Post) and at follow-up 6 months following post-intervention testing. The present RCT will be conducted as a multicentre parallel-group superiority of intervention study with assessor-blinding and a stratified block randomisation design. Following pre-intervention testing, participants in the RCT study will be randomised into robot-assisted training (intervention) or standard training (active control). Participants in both groups will train 1:1 with a physiotherapist two times a week for 6 months (groups are matched for time allocated to training). The primary outcome is the between-group difference in change score of Fugl-Meyer Lower Extremity Assessment from pre-post intervention on the intention-to-treat population. A per-protocol analysis will be conducted analysing the differences in change scores of the participants demonstrating acceptable adherence. A priori sample size calculation allowing the detection of the minimally clinically important between-group difference of 6 points in the primary outcome (standard deviation 6 point, α = 5% and ß = 80%) resulted in 34 study participants. Allowing for dropout the study will include 40 participants in total. DISCUSSION: For stroke-affected individuals still suffering from moderate to severe disabilities following subacute standard rehabilitation, training interventions based on dynamic robot-assisted body weight unloading may facilitate an appropriate intensity, volume and task-specificity in training leading to superior functional recovery compared to training without the use of body weight unloading. TRIAL REGISTRATION: ClinicalTrials.gov. NCT06273475. TRIAL STATUS: Recruiting. Trial identifier: NCT06273475. Registry name: ClinicalTrials.gov. Date of registration on ClinicalTrials.gov: 22/02/2024.

COVID-19-associated cerebral microbleeds in the general population.

Cerebral microbleeds are frequent incidental findings on brain MRI and have previously been shown to occur in Coronavirus Disease 2019 (COVID-19) cohorts of critically ill patients. We aimed to determine the risk of having microbleeds on medically indicated brain MRI and compare non-hospitalized COVID-19-infected patients with non-infected controls. In this retrospective case-control study, we included patients over 18 years of age, having an MRI with a susceptibility-weighted sequence, between 1 January 2019 and 1 July 2021. Cases were identified based on a positive reverse transcriptase polymerase chain reaction test for SARS-CoV-2 and matched with three non-exposed controls, based on age, sex, body mass index and comorbidities. The number of cerebral microbleeds on each scan was determined using artificial intelligence. We included 73 cases and 219 matched non-exposed controls. COVID-19 was associated with significantly greater odds of having cerebral microbleeds on MRI [odds ratio 2.66 (1.23-5.76, 95% confidence interval)], increasingly so when patients with dementia and hospitalized patients were excluded. Our findings indicate that cerebral microbleeds may be associated with COVID-19 infections. This finding may add to the pathophysiological considerations of cerebral microbleeds and help explain cases of incidental cerebral microbleeds in patients with previous COVID-19.

Artificial intelligence for MRI stroke detection: a systematic review and meta-analysis.

OBJECTIVES: This systematic review and meta-analysis aimed to assess the stroke detection performance of artificial intelligence (AI) in magnetic resonance imaging (MRI), and additionally to identify reporting insufficiencies. METHODS: PRISMA guidelines were followed. MEDLINE, Embase, Cochrane Central, and IEEE Xplore were searched for studies utilising MRI and AI for stroke detection. The protocol was prospectively registered with PROSPERO (CRD42021289748). Sensitivity, specificity, accuracy, and area under the receiver operating characteristic (ROC) curve were the primary outcomes. Only studies using MRI in adults were included. The intervention was AI for stroke detection with ischaemic and haemorrhagic stroke in separate categories. Any manual labelling was used as a comparator. A modified QUADAS-2 tool was used for bias assessment. The minimum information about clinical artificial intelligence modelling (MI-CLAIM) checklist was used to assess reporting insufficiencies. Meta-analyses were performed for sensitivity, specificity, and hierarchical summary ROC (HSROC) on low risk of bias studies. RESULTS: Thirty-three studies were eligible for inclusion. Fifteen studies had a low risk of bias. Low-risk studies were better for reporting MI-CLAIM items. Only one study examined a CE-approved AI algorithm. Forest plots revealed detection sensitivity and specificity of 93% and 93% with identical performance in the HSROC analysis and positive and negative likelihood ratios of 12.6 and 0.079. CONCLUSION: Current AI technology can detect ischaemic stroke in MRI. There is a need for further validation of haemorrhagic detection. The clinical usability of AI stroke detection in MRI is yet to be investigated. CRITICAL RELEVANCE STATEMENT: This first meta-analysis concludes that AI, utilising diffusion-weighted MRI sequences, can accurately aid the detection of ischaemic brain lesions and its clinical utility is ready to be uncovered in clinical trials. KEY POINTS: There is a growing interest in AI solutions for detection aid. The performance is unknown for MRI stroke assessment. AI detection sensitivity and specificity were 93% and 93% for ischaemic lesions. There is limited evidence for the detection of patients with haemorrhagic lesions. AI can accurately detect patients with ischaemic stroke in MRI.

Long-term colchicine for the prevention of vascular recurrent events in non-cardioembolic stroke (CONVINCE): a randomised controlled trial.

BACKGROUND: Anti-inflammatory therapy with long-term colchicine prevented vascular recurrence in coronary disease. Unlike coronary disease, which is typically caused by atherosclerosis, ischaemic stroke is caused by diverse mechanisms including atherosclerosis and small vessel disease or is frequently due to an unknown cause. We aimed to investigate the hypothesis that long-term colchicine would reduce recurrent events after ischaemic stroke. METHODS: We did a randomised, parallel-group, open-label, blinded endpoint assessed trial comparing long-term colchicine (0·5 mg orally per day) plus guideline-based usual care with usual care only. Hospital-based patients with non-severe, non-cardioembolic ischaemic stroke or high-risk transient ischaemic attack were eligible. The primary endpoint was a composite of first fatal or non-fatal recurrent ischaemic stroke, myocardial infarction, cardiac arrest, or hospitalisation (defined as an admission to an inpatient unit or a visit to an emergency department that resulted in at least a 24 h stay [or a change in calendar date if the hospital admission or discharge times were not available]) for unstable angina. The p value for significance was 0·048 to adjust for two prespecified interim analyses conducted by the data monitoring committee, for which the steering committee and trial investigators remained blinded. The trial was registered at ClinicalTrials.gov (NCT02898610) and is completed. FINDINGS: 3154 patients were randomly assigned between Dec 19, 2016, and Nov 21, 2022, with the last follow-up on Jan 31, 2024. The trial finished before the anticipated number of outcomes was accrued (367 outcomes planned) due to budget constraints attributable to the COVID-19 pandemic. Ten patients withdrew consent for analysis of their data, leaving 3144 patients in the intention-to-treat analysis: 1569 (colchicine and usual care) and 1575 (usual care alone). A primary endpoint occurred in 338 patients, 153 (9·8%) of 1569 patients allocated to colchicine and usual care and 185 (11·7%) of 1575 patients allocated to usual care alone (incidence rates 3·32 vs 3·92 per 100 person-years, hazard ratio 0·84; 95% CI 0·68-1·05, p=0·12). Although no between-group difference in C-reactive protein (CRP) was observed at baseline, patients treated with colchicine had lower CRP at 28 days and at 1, 2, and 3 years (p<0·05 for all timepoints). The rates of serious adverse events were similar in both groups. INTERPRETATION: Although no statistically significant benefit was observed on the primary intention-to-treat analysis, the findings provide new evidence supporting the rationale for anti-inflammatory therapy in further randomised trials. FUNDING: Health Research Board Ireland, Deutsche Forschungsgemeinschaft (German Research Foundation), and Fonds Wetenschappelijk Onderzoek Vlaanderen (Research Foundation Flanders), Belgium.

Quality of early stroke care and long-term mortality in patients with acute stroke: A nationwide follow-up study.

INTRODUCTION: High quality of early stroke care is essential for optimizing the chance of a good patient outcome. The quality of care may be monitored by process performance measures (PPMs) and previous studies have found an association between fulfilment of PPMs and short-term mortality. However, the association with long-term mortality remains to be determined. We aimed to evaluate the association between fulfilment of PPMs and long-term mortality for patients with acute stroke in Denmark. PATIENTS AND METHODS: We used data from Danish health care registers between 2008 and 2020 to identify all patients admitted with incident stroke (haemorrhagic (ICH) or ischaemic stroke). The quality of early stroke care was assessed using 10 PPMs. Mortality was compared using Cox proportional hazard ratios, risk ratios computed using Poisson regression, and standardized relative survival. RESULTS: We included 102,742 patients; 9804 cases of ICH, 88,591 cases of ischaemic stroke, and 4347 cases of unspecified strokes. The cumulative 10-year mortality risk was 56.8%. Fulfilment of the individual PPMs was associated with adjusted hazard rate ratios of death between 0.76 and 0.96. Patients with 100% fulfilment of all PPMs had a lower 10-year post-stroke mortality (adjusted risk ratio 0.90) compared to the patients with 0%-49% fulfilment and a standardized relative survival of 81.3%, compared to the general population. CONCLUSION: High quality of early stroke care was associated with lower long-term mortality following both ICH and ischaemic stroke, which emphasizes the importance of continued attention on the ability of stroke care providers to deliver high quality of early care.

Prognosis and antithrombotic practice patterns in patients with recurrent and transient atrial fibrillation following acute coronary syndrome: A nationwide study.

BACKGROUND: First-time detected atrial fibrillation (AF) is associated with aggravated prognosis in patients admitted with acute coronary syndrome (ACS). Yet, among patients surviving beyond one year after ACS, it remains unclear how the recurrence of AF within the initial year after ACS affects the risk of stroke. METHODS: With Danish nationwide data from 2000 to 2021, we identified all patients with first-time ACS who were alive one year after discharge (index date). Patients were categorized into: i) no AF; ii) first-time detected AF during ACS admission without a recurrent hospital contact with AF (transient AF); and iii) first-time detected AF during ACS admission with a subsequent recurrent hospital contact with AF (recurrent AF). From index date, two-year rates of ischemic stroke were compared using multivariable adjusted Cox regression analysis. Treatment with antithrombotic therapy was assessed as filled prescriptions between 12 and 15 months following ACS discharge. RESULTS: We included 139,137 patients surviving one year post ACS discharge: 132,944 (95.6%) without AF, 3920 (2.8%) with transient AF, and 2273 (1.6%) with recurrent AF. Compared to those without AF, the adjusted two-year hazard ratios of ischemic stroke were 1.45 (95% CI, 1.22-1.71) for patients with transient AF and 1.47 (95% CI: 1.17-1.85) for patients with recurrent AF. Prescription rates of oral anticoagulation increased over calendar time, reaching 68.3% and 78.7% for transient and recurrent AF, respectively, from 2019 to 2021. CONCLUSION: In patients surviving one year after ACS with first-time detected AF, recurrent and transient AF were associated with a similarly increased long-term rate of ischemic stroke.

Emergency Medical Services dispatcher recognition of stroke: A systematic review.

PURPOSE: Stroke treatments are time-sensitive, and thus early and correct recognition of stroke by Emergency Medical Services is essential for outcomes. This is particularly important with the adaption of mobile stroke units. In this systematic review, we therefore aimed to provide a comprehensive overview of Emergency Medical Services dispatcher recognition of stroke. METHODS: The review was registered on PROSPERO and the PRISMA guidelines were applied. We searched PubMed, Embase, and Cochrane Review Library. Screening and data extraction were performed by two observers. Risk of bias was assessed using the QUADAS-2 instrument. FINDINGS: Of 1200 papers screened, 24 fulfilled the inclusion criteria. Data on sensitivity was reported in 22 papers and varied from 17.9% to 83.0%. Positive predictive values were reported in 12 papers and ranged from 24.0% to 87.7%. Seven papers reported specificity, which ranged from 20.0% to 99.1%. Six papers reported negative predictive value, ranging from 28.0% to 99.4%. In general, the risk of bias was low. DISCUSSION: Stroke recognition by dispatchers varied greatly, but overall many patients with stroke are not recognised, despite the initiatives taken to improve stroke literacy. The available data are of high quality, however Asian, African, and South American populations are underrepresented. CONCLUSION: While the data are heterogenous, this review can serve as a reference for future research in emergency medical dispatcher stroke recognition and initiatives to improve prehospital stroke recognition.

Diagnosing cancer-associated ischemic stroke: A systematic review of hematological biomarkers.

BACKGROUND AND AIM: Patients suffering from cancer are reported to have an increased risk of ischemic stroke (IS). We aimed to identify cancer-associated biomarkers found to differentiate between IS associated with cancer from those not associated with cancer. SUMMARY OF REVIEW: We performed a systematic search of PubMed and EMBASE databases according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The study is reported in PROSPERO (#CRD42022355129). In total, 5563 papers were screened, of which 49 papers were included. Seven biomarkers were identified which had the potential to differentiate between patients who had cancer or stroke or both conditions. D-dimer was the most frequently monitored biomarker, and high levels were significantly associated with cancer-related strokes in (42/44) studies. Fibrinogen was significantly associated with cancer-related strokes in 11/27 studies. A higher level of C-reactive protein, investigated in 19 studies, was associated with cancer-related strokes, but conclusive multivariate analysis was not performed. Finally, the four cancer-associated antigens CA125, CA153, CA199, and carcinoembryonic antigen were only reported on in three to six studies, respectively. These studies all originated from the Guangxi province in China. CA125 was associated with an increased risk of IS in four of six studies. CONCLUSION: Increased D-dimer seems associated with cancer-related IS. CRP may also be a candidate as a cancer-associated stroke biomarker, but this requires further verification. Fibrinogen and the more specific cancer biomarkers have not yet been proven helpful for detecting cancer-related strokes.

A retrospective study on machine learning-assisted stroke recognition for medical helpline calls.

Advanced stroke treatment is time-dependent and, therefore, relies on recognition by call-takers at prehospital telehealth services to ensure fast hospitalisation. This study aims to develop and assess the potential of machine learning in improving prehospital stroke recognition during medical helpline calls. We used calls from 1 January 2015 to 31 December 2020 in Copenhagen to develop a machine learning-based classification pipeline. Calls from 2021 are used for testing. Calls are first transcribed using an automatic speech recognition model and then categorised as stroke or non-stroke using a text classification model. Call-takers achieve a sensitivity of 52.7% (95% confidence interval 49.2-56.4%) with a positive predictive value (PPV) of 17.1% (15.5-18.6%). The machine learning framework performs significantly better (p < 0.0001) with a sensitivity of 63.0% (62.0-64.1%) and a PPV of 24.9% (24.3-25.5%). Thus, a machine learning framework for recognising stroke in prehospital medical helpline calls may become a supportive tool for call-takers, aiding in early and accurate stroke recognition.

Diagnostic test accuracy study of a commercially available deep learning algorithm for ischemic lesion detection on brain MRIs in suspected stroke patients from a non-comprehensive stroke center.

PURPOSE: To estimate the ability of a commercially available artificial intelligence (AI) tool to detect acute brain ischemia on Magnetic Resonance Imaging (MRI), compared to an experienced neuroradiologist. METHODS: We retrospectively included 1030 patients with brain MRI, suspected of stroke from January 6th, 2020 to 1st of April 2022, based on these criteria: Age ≥ 18 years, symptoms within four weeks before the scan. The neuroradiologist reinterpreted the MRI scans and subclassified ischemic lesions for reference. We excluded scans with interpretation difficulties due to artifacts or missing sequences. Four MRI scanner models from the same vendor were used. The first 800 patients were included consecutively, remaining enriched for less frequent lesions. The index test was a CE-approved AI tool (Apollo version 2.1.1 by Cerebriu). RESULTS: The final analysis cohort comprised 995 patients (mean age 69 years, 53 % female). A case-based analysis for detecting acute ischemic lesions showed a sensitivity of 89 % (95 % CI: 85 %-91 %) and specificity of 90 % (95 % CI: 87 %-92 %). We found no significant difference in sensitivity or specificity based on sex, age, or comorbidities. Specificity was reduced in cases with DWI artifacts. Multivariate analysis showed that increasing ischemic lesion size and fragmented lesions were independently associated with higher sensitivity, while non-acute lesion ages lowered sensitivity. CONCLUSIONS: The AI tool exhibits high sensitivity and specificity in detecting acute ischemic lesions on MRI compared to an experienced neuroradiologist. While sensitivity depends on the ischemic lesions' characteristics, specificity depends on the image quality.

Dispatcher Stroke/TIA Recognition in Emergency Medical Call Center and Out-of-Hours Service Calls in Copenhagen, Denmark.

Background and Objectives: Recognition of stroke/TIA symptoms by emergency medical services (EMS) is instrumental in providing timely recanalization treatments. We assessed the recognition of stroke/TIA by EMS via the emergency medical call center (EMCC) dispatchers and out-of-hours health service (OOHS) dispatchers. Methods: In a registry study, based on 2015-2020 data from the Copenhagen EMS, we calculated sensitivity, positive predictive value (PPV), specificity, and negative predictive value (NPV) of dispatcher suspicion of stroke or transient ischemic attack (TIA) and compared against discharge diagnosis. Results: We included 462,029 contacts to EMCC and 2,573,865 contacts to OOHS. In total, 19,798 contacts had a stroke or TIA diagnosis at hospital discharge. Sensitivity was 0.64 for EMCC dispatchers and 0.25 for OOHS. PPV was 0.28 for EMCC and 0.22 for OOHS; specificity was 0.96 for EMCC and >0.99 for OOHS, and NPV was 0.99 for EMCC and >0.99 for OOHS. Sensitivity improved over the period of the study from 0.62 to 0.68 for EMCC and from 0.20 to 0.25 for OOHS. PPV did not change over the period for EMCC and decreased from 0.26 to 0.19 for OOHS. Both EMCC and OOHS more frequently overlooked stroke in women, in patients calling more than 3 hours after symptom onset, and for more severe strokes. For OHHS, advanced age correlated with lower recognition. Discussion: As the first study reporting on OOHS setting dispatcher stroke/TIA recognition, we find a need for the improvement of stroke/TIA recognition both in EMCC and in OOHS. Solutions may include specific training of dispatchers, public awareness campaigns, and new technological solutions.

Testing the cognitive effects of tadalafil. Neuropsychological secondary outcomes from the PASTIS trial.

Cerebral small vessel disease (SVD) is a major cause of cognitive impairment in older people. As secondary endpoints in a phase-2 randomised clinical trial, we tested the effects of single administration of a widely-used PDE5 inhibitor, tadalafil, on cognitive performance in older people with SVD. In a double-blinded, placebo-controlled, cross-over trial, participants received tadalafil (20 mg) and placebo on two visits ≥ 7 days apart (randomised to order of treatment). The Montreal Cognitive Assessment (MOCA) was administered at baseline, alongside a measure to estimate optimal intellectual ability (Test of Premorbid Function). Then, before and after treatment, a battery of neuropsychological tests was administered, assessing aspects of attention, information processing speed, working memory and executive function. Sixty-five participants were recruited and 55 completed the protocol (N = 55, age: 66.8 (8.6) years, range 52-87; 15/40 female/male). Median MOCA score was 26 (IQR: 23, 27], range 15-30). No significant treatment effects were seen in any of the neuropsychological tests. There was a trend towards improved performance on Digit Span Forward (treatment effect 0.37, C.I. 0.01, 0.72; P = 0.0521). We did not identify significant treatment effects of single-administration tadalafil on neuropsychological performance in older people with SVD. The trend observed on Digit Span Forward may help to inform future studies. Clinical trial registration: http://www.clinicaltrials.gov. Unique identifier: NCT00123456, https://eudract.ema.europa.eu. Unique identifier: 2015-001,235-20NCT00123456.

Long-Term Incidence of Ischemic Stroke After Transient Ischemic Attack: A Nationwide Study From 2014 to 2020.

BACKGROUND: The short-term incidence of ischemic stroke after a transient ischemic attack (TIA) is high. However, data on the long-term incidence are not well known but are needed to guide preventive strategies. METHODS: Patients with first-time TIA (index date) in the Danish Stroke Registry (January 2014-December 2020) were included and matched 1:4 with individuals from the background population and 1:1 with patients with a first-time ischemic stroke on the basis of age, sex, and calendar year. The incidences of ischemic stroke and mortality from index date were estimated by Aalen-Johansen and Kaplan-Meier estimators, respectively, and compared between groups using multivariable Cox regression. RESULTS: We included 21 500 patients with TIA, 86 000 patients from the background population, and 21 500 patients with ischemic stroke (median age, 70.8 years [25th-75th percentile, 60.8-78.7]; 53.1% males). Patients with TIA had more comorbidities than the background population, yet less than the control stroke population. The 5-year incidence of ischemic stroke after TIA (6.1% [95% CI, 5.7-6.5]) was higher than the background population (1.5% [95% CI, 1.4-1.6], P<0.01; hazard ratio, 5.14 [95% CI, 4.65-5.69]) but lower than the control stroke population (8.9% [95% CI, 8.4-9.4], P<0.01; hazard ratio, 0.58 [95% CI, 0.53-0.64]). The 5-year mortality for patients with TIA (18.6% [95% CI, 17.9-19.3]) was higher than the background population (14.8% [95% CI, 14.5-15.1], P<0.01; hazard ratio, 1.26 [95% CI, 1.20-1.32]) but lower than the control stroke population (30.1% [95% CI, 29.3-30.9], P<0.01; hazard ratio, 0.41 [95% CI, 0.39-0.44]). CONCLUSIONS: Patients with first-time TIA had an ischemic stroke incidence of 6.1% during the 5-year follow-up period. After adjustment for relevant comorbidities, this incidence was approximately 5-fold higher than what was found for controls in the background population and 40% lower than for patients with recurrent ischemic stroke.

Recognition of visual symptoms in stroke: a challenge to patients, bystanders, and Emergency Medical Services.

BACKGROUND: Identification of visual symptoms as a sign of acute stroke can be challenging for both first line healthcare professionals and lay persons. Failed recognition of visual symptoms by medical dispatchers at the Emergency Medical Dispatch Center (EMDC-112) or personnel at the Out-of-Hours Health Service (OOHS) may delay stroke revascularization. We aimed to identify correct system response to visual symptoms in emergency calls. METHODS: Phone calls from patient or bystander to the EMDC-112 or OOHS, which included visual symptoms on patients later verified with stroke/Transient ischemic attack (TIA) diagnosis, were analyzed. Data were stratified according to hospitalization within and after 4.5 h from symptom onset. Descriptive and multiple logistic regression analysis were performed. RESULTS: Of 517 calls identified, 290 calls fulfilled inclusion criteria. Only 30% of the patients received correct visitation by the medical dispatchers and referral to the hospital by a high-priority ambulance. Correct visitation was associated with early contact (adjusted OR: 2.37, 95% CI: 1.11, 5.03), contact to the EMDC-112 (adjusted OR: 3.18, 95% CI: 1.80, 5.62), and when the medical dispatcher asked additional questions on typical stroke symptoms (adjusted OR: 6.36, 95% CI: 3.01, 13.43). No specific visual symptom was associated with stroke recognition and fast hospitalization. CONCLUSIONS: First line healthcare professionals had significant problems in identifying visual symptoms as a sign of acute stroke and eliciting correct response. This highlights an urgent need to improve knowledge of visual symptoms in acute stroke and emphasize correct response to stroke symptoms in general.

The left atrial appendage closure by surgery-2 (LAACS-2) trial protocol rationale and design of a randomized multicenter trial investigating if left atrial appendage closure prevents stroke in patients undergoing open-heart surgery irrespective of preoperative atrial fibrillation status and stroke risk.

BACKGROUND: Current recommendations regarding the use of surgical left atrial appendage (LAA) closure to prevent thromboembolisms lack high-level evidence. Patients undergoing open-heart surgery often have several cardiovascular risk factors and a high occurrence of postoperative atrial fibrillation (AF)-with a high recurrence rate-and are thus at a high risk of stroke. Therefore, we hypothesized that concomitant LAA closure during open-heart surgery will reduce mid-term risk of stroke independently of preoperative AF status and CHA2DS2-VASc score. METHODS: This protocol describes a randomized multicenter trial. Consecutive participants ≥18 years scheduled for first-time planned open-heart surgery from cardiac surgery centers in Denmark, Spain, and Sweden are included. Both patients with a previous diagnosis of paroxysmal or chronic AF, as well as those without AF, are eligible to participate, irrespective of their CHA2DS2-VASc score. Patients already planned for ablation or LAA closure during surgery, with current endocarditis, or where follow-up is not possible are considered noneligible. Patients are stratified by site, surgery type, and preoperative or planned oral anticoagulation treatment. Subsequently, patients are randomized 1:1 to either concomitant LAA closure or standard care (ie, open LAA). The primary outcome is stroke, including transient ischemic attack, as assigned by 2 independent neurologists blinded to the treatment allocation. To recognize a 60% relative risk reduction of the primary outcome with LAA closure, 1,500 patients are randomized and followed for 2 years (significance level of 0.05 and power of 90%). CONCLUSIONS: The LAACS-2 trial is likely to impact the LAA closure approach in most patients undergoing open-heart surgery. TRIAL REGISTRATION: NCT03724318.

Visual symptoms in acute stroke - A systematic review of observational studies.

OBJECTIVE: Atypical symptoms of stroke, such as non-specific visual symptoms, are a challenging aspect of acute stroke diagnostics. Among patients evaluated for stroke in the Emergency Department, 2-28% present with stroke chameleons, and 30-43% with stroke mimics. We aimed to identify the type of visual symptoms present in typical strokes, stroke mimics, and stroke chameleons. PATIENTS AND METHODS: By use of Preferred Reporting Items for Systematic Reviews and Meta-Analysis we searched PubMed and Embase for studies with reports of acute visual symptoms in typical strokes vs mimics or chameleons (PROSPERO protocol, ID CRD42022364749). Risk of bias was assessed by The Critical Appraisal Skills Program. RESULTS: Thirteen papers were included, comprising data from 9248 patients evaluated for stroke. Compared to mimics, visual symptoms in stroke presented more frequently as hemianopia (28.2% vs 4.8%, 7,4% vs 2.3%, 22% vs 0%), visual loss (11.6% vs 1.8%), visual field defect (11.6% vs 4%, 24% vs 2%, 19% vs 1.7%), eye movement disorder (19.4% vs 6.4%), eye deviation (9.6% vs 0.9%), gaze palsy (32.1% vs 8.6%), oculomotor disturbance (37% vs 0%), and visual inattention (17.5% vs 4%). Compared to strokes, mimics more often presented "non-systematized visual trouble" (10% vs 3%) and blurred vision (22% vs 5%), whereas "visual disturbance" was reported more often in stroke chameleons than in typical strokes (10% vs 3%). CONCLUSION: Detailed reports of visual symptoms were lacking in most studies, however blurred vision and "non-systematized visual trouble" were more frequent in mimics, "visual disturbance" in stroke chameleons, and negative visual symptoms such as visual field defects in typical strokes. A more systematic and detailed approach to visual symptoms may facilitate acute stroke recognition in patients with visual symptoms.

Quality in stroke care during the early phases of the COVID-19 pandemic: A nationwide study.

Introduction: Evidence-based early stroke care as reflected by fulfillment of process performance measures, is strongly related to better patient outcomes after stroke and transient ischemic attack (TIA). Detailed data on the resilience of stroke care services during the COVID-19 pandemic are limited. We aimed to examine the quality of early stroke care at Danish hospitals during the early phases of the COVID-19 pandemic. Materials and methods: We extracted data from Danish national health registries in five time periods (11 March, 2020-27 January, 2021) and compared these to a baseline pre-pandemic period (13 March, 2019-10 March, 2020). Quality of early stroke care was assessed as fulfilment of individual process performance measures and as a composite measure (opportunity-based score). Results: A total of 23,054 patients were admitted with stroke and 8153 with a TIA diagnosis in the entire period. On a national level, the opportunity-based score (95% confidence interval [CI]) at baseline for ischemic patients was 81.1% (80.8-81.4), for intracerebral hemorrhage (ICH) 85.5% (84.3-86.6), and for TIA 96.0% (95.3-96.1). An increase of 1.1% (0.1-2.2) and 1.5% (0.3-2.7) in the opportunity-based score was observed during the first national lockdown period for AIS and TIA followed by a decline of -1.3% (-2.2 to -0.4) in the gradual reopening phase for AIS indicators. We found a significant negative association between regional incidence rates and quality-of-care in ischemic stroke patients implying that quality decreases when admission rates increase. Conclusion: The quality of acute stroke/TIA care in Denmark remained high during the early phases of the pandemic and only minor fluctuations occurred.

Patient-tailored transcranial direct current stimulation to improve stroke rehabilitation: study protocol of a randomized sham-controlled trial.

BACKGROUND: Many patients do not fully regain motor function after ischemic stroke. Transcranial direct current stimulation (TDCS) targeting the motor cortex may improve motor outcome as an add-on intervention to physical rehabilitation. However, beneficial effects on motor function vary largely among patients within and across TDCS trials. In addition to a large heterogeneity of study designs, this variability may be caused by the fact that TDCS was given as a one-size-fits-all protocol without accounting for anatomical differences between subjects. The efficacy and consistency of TDCS might be improved by a patient-tailored design that ensures precise targeting of a physiologically relevant area with an appropriate current strength. METHODS: In a randomized, double-blinded, sham-controlled trial, patients with subacute ischemic stroke and residual upper-extremity paresis will receive two times 20 min of focal TDCS of ipsilesional primary motor hand area (M1-HAND) during supervised rehabilitation training three times weekly for 4 weeks. Anticipated 60 patients will be randomly assigned to active or sham TDCS of ipsilesional M1-HAND, using a central anode and four equidistant cathodes. The placement of the electrode grid on the scalp and current strength at each cathode will be personalized based on individual electrical field models to induce an electrical current of 0.2 V/m in the cortical target region resulting in current strengths between 1 and 4 mA. Primary endpoint will be the difference in change of Fugl-Meyer Assessment of Upper Extremity (FMA-UE) score between active TDCS and sham at the end of the intervention. Exploratory endpoints will include UE-FMA at 12 weeks. Effects of TDCS on motor network connectivity and interhemispheric inhibition will be assessed with functional MRI and transcranial magnetic stimulation. DISCUSSION: The study will show the feasibility and test the efficacy of personalized, multi-electrode anodal TDCS of M1-HAND in patients with subacute stroke patients with upper-extremity paresis. Concurrent multimodal brain mapping will shed light into the mechanisms of action of therapeutic personalized TDCS of M1-HAND. Together, the results from this trial may inform future personalized TDCS studies in patients with focal neurological deficits after stroke.

Biomarkers predictive of atrial fibrillation in patients with cryptogenic stroke. Insights from the Nordic Atrial Fibrillation and Stroke (NOR-FIB) study.

BACKGROUND AND PURPOSE: There are currently no biomarkers to select cryptogenic stroke (CS) patients for monitoring with insertable cardiac monitors (ICMs), the most effective tool for diagnosing atrial fibrillation (AF) in CS. The purpose of this study was to assess clinically available biomarkers as predictors of AF. METHODS: Eligible CS and cryptogenic transient ischaemic attack patients underwent 12-month monitoring with ICMs, clinical follow-up and biomarker sampling. Levels of cardiac and thromboembolic biomarkers, taken within 14 days from symptom onset, were compared between patients diagnosed with AF (n = 74) during monitoring and those without AF (n = 185). Receiver operating characteristic curves were created. Biomarkers reaching area under the receiver operating characteristic curve ≥ 0.7 were dichotomized by finding optimal cut-off values and were used in logistic regression establishing their predictive value for increased risk of AF in unadjusted and adjusted models. RESULTS: B-type natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptide (NT-proBNP), creatine kinase, D-dimer and high-sensitivity cardiac troponin I and T were significantly higher in the AF than non-AF group. BNP and NT-proBNP reached the predefined area under the curve level, 0.755 and 0.725 respectively. Optimal cut-off values were 33.5 ng/l for BNP and 87 ng/l for NT-proBNP. Regression analysis showed that NT-proBNP was a predictor of AF in both unadjusted (odds ratio 7.72, 95% confidence interval 3.16-18.87) and age- and sex-adjusted models (odds ratio 4.82, 95% confidence interval 1.79-12.96). CONCLUSION: Several clinically established biomarkers were associated with AF. NT-proBNP performed best as AF predictor and could be used for selecting patients for long-term monitoring with ICMs.

High-intensity training in patients with lacunar stroke: A one-year follow-up.

OBJECTIVES: Physical inactivity is a major risk factor for stroke. It is a challenge for patients to initiate and adhere to regular exercise post-stroke. Early initiation of home-based high-intensity interval training (HIIT) may engage patients in physical activity, improve cardiorespiratory fitness, and reduce risk of recurrent stroke. MATERIALS AND METHODS: Post-intervention follow-up of patients with lacunar stroke, randomized to three-months HIIT including weekly motivational calls, or usual care. At follow-up (six- and 12-months post-stroke), we investigated changes in cardiorespiratory fitness, physical activity, fatigue, depression, mental well-being, stress, cognition, cardiovascular function, and recurrent stroke. RESULTS: We included 71 patients of whom 59 patients (mean age: 63.9 ± 8.8 years) completed six- and 12-month follow-up. No change was detected in cardiorespiratory fitness between groups from baseline to 12-months follow-up. At six months, vigorous-intensity activity (median hours/week [interquartile range]) was maintained in the intervention group (baseline, 0[0;2]; post-intervention, 2[0;3]; six-month, 2[0;4]) and increased in the usual care group (baseline, 0[0;1]; post-intervention, 1[0;2]; six-month, 1[0;3]), with no difference between groups. Vigorous-intensity activity declined to baseline levels at 12-months in both groups. Secondary outcomes improved from baseline to 12-months with no significant differences between groups. Similar rate of recurrent stroke (n=3) occurred in each group with a three-month delay in the intervention group. CONCLUSIONS: Early initiated HIIT did not increase long-term cardiorespiratory fitness, but increased time spent doing vigorous-intensity activities post-stroke. Decline to baseline activity level at 12 months warrants identification of motivators to initiate and sustain physical activity post-stroke.