High prevalence of erectile dysfunction in male patients with acute stroke was associated with age but not to modifiable cardiovascular risk factors.

Background: Erectile dysfunction (ED) and stroke share common risk factors, and symptoms of ED often precede the development of clinical cardiovascular disease (CVD). However, little is known about how ED is associated with cardiovascular (CV) risk factors in patients who had a stroke and if concomitant ED is a marker of more severe CVD. Aims: We aimed to identify the prevalence of ED and CV risk factors in patients admitted with a stroke or transient ischaemic attack (TIA). Further, we wanted to test if self-reported ED associated with presence of CV risk factors, and if patients with ED had increased stroke severity compared with patients without ED. Methods: This was a post hoc analysis of data retrieved in a cross-sectional survey from two non-comprehensive stroke units in Denmark. Multiple logistic regression adjusted for covariates was performed to investigate the association between CV risk factors and self-reported ED. Results: We included 287 male patients of which 116 (40.4%) had self-reported ED. Advanced age was significantly associated with self-reported ED (reference ≤60 years: OR 3.93, 95% CI 1.84 to 8.37 for men 71-80 years and OR 4.61, 95% CI 1.92 to 11.08 for men >80 years). Self-reported ED was not significantly associated with CV risk factors or stroke severity. Discussion: Four in 10 men with acute stroke or TIA reported to have ED prior to their stroke, and this was associated with age rather than CV risk factors. Hence, self-reported ED was not restricted to the CVD load, nor was ED a risk marker for increased stroke severity. However, our population was of high age with well-established CVD, and the presence of ED may be a stroke risk marker in younger patients who had a stroke. Based on the prevalence, potential treatment of ED should be addressed in stroke recovery.

Cerebral blood flow and cognition after 3 months tadalafil treatment in small vessel disease (ETLAS-2): study protocol for a randomized controlled trial.

BACKGROUND: Targeted treatment is highly warranted for cerebral small vessel disease, a causal factor of one in four strokes and a major contributor to vascular dementia. Patients with cerebral small vessel disease have impaired cerebral blood flow and vessel reactivity. Tadalafil is a specific phosphodiesterase 5 inhibitor shown to improve vascular reactivity in the brain. METHODS: The ETLAS-2 trial is a phase 2 double-blind, randomized placebo-controlled, parallel trial with the feasibility of tadalafil as the primary outcome. The trial aims to include 100 patients with small vessel occlusion stroke or transitory ischemic attacks and signs of cerebral small vessel disease more than 6 months before administration of study medication. Patients are treated for 3 months with tadalafil 20 mg or placebo daily and undergo magnetic resonance imaging (MRI) to evaluate changes in small vessel disease according to the STandards for ReportIng Vascular changes on nEuroimaging (STRIVE) criteria as well as cerebral blood flow, cerebrovascular reactivity, and neurovascular coupling in a functional MRI sub-study. The investigation includes comprehensive cognitive testing using paper-pencil tests and Cambridge Neuropsychological Test Automated Battery (CANTAB) tests in a cognitive sub-study. DISCUSSION: The ETLAS-2 trial tests the feasibility of long-term treatment with tadalafil and explores vascular and cognitive effects in cerebral small vessel disease in trial sub-studies. The study aims to propose a new treatment target and improve the understanding of small vessel disease. Currently, 64 patients have been included and the trial is estimated to be completed in the year 2024. TRIAL REGISTRATION: Clinicaltrials.gov, NCT05173896. Registered on 30 December 2021.

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.

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.

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.

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.