Stroke frequency, associated factors, and clinical features in primary systemic vasculitis: a multicentric observational study.

OBJECTIVES: The cerebral vessels may be affected in primary systemic vasculitis (PSV), but little is known about cerebrovascular events (CVEs) in this population. This study aimed to determine the frequency of CVEs at the time of diagnosis of PSV, to identify factors associated with CVEs in PSV, and to explore features and outcomes of stroke in patients with PSV. METHODS: Data from adults newly diagnosed with PSV within the Diagnostic and Classification Criteria in VASculitis (DCVAS) study were analysed. Demographics, risk factors for vascular disease, and clinical features were compared between patients with PSV with and without CVE. Stroke subtypes and cumulative incidence of recurrent CVE during a prospective 6-month follow-up were also assessed. RESULTS: The analysis included 4828 PSV patients, and a CVE was reported in 169 (3.50%, 95% CI 3.00-4.06): 102 (2.13% 95% CI 1.73-2.56) with stroke and 81 (1.68% 95% CI 1.33-2.08) with transient ischemic attack (TIA). The frequency of CVE was highest in Behçet's disease (9.5%, 95% CI 5.79-14.37), polyarteritis nodosa (6.2%, 95% CI 3.25-10.61), and Takayasu's arteritis (6.0%, 95% CI 4.30-8.19), and lowest in microscopic polyangiitis (2.2%, 95% CI 1.09-3.86), granulomatosis with polyangiitis (2.0%, 95% CI 1.20-3.01), cryoglobulinaemic vasculitis (1.9%, 95% CI 0.05-9.89), and IgA-vasculitis (Henoch-Schönlein) (0.4%, 95% CI 0.01-2.05). PSV patients had a 11.9% cumulative incidence of recurrent CVE during a 6-month follow-up period. CONCLUSION: CVEs affect a significant proportion of patients at time of PSV diagnosis, and the frequency varies widely among different vasculitis, being higher in Behçet's. Overall, CVE in PSV is not explained by traditional vascular risk factors and has a high risk of CVE recurrence.

Neglect scoring modifications in the National Institutes of Health Stroke Scale improve right hemisphere stroke lesion volume prediction.

BACKGROUND: The National Institutes of Health Stroke Scale (NIHSS) does not equitably assess stroke severity in the two cerebral hemispheres. By attributing a maximum of two points for neglect and seven for language, it undervalues right hemisphere deficits. We aimed to investigate if NIHSS equally predicts right hemisphere lesion volumes in patients with and without neglect, and if a modification of the neglect scoring rules could increase its predictive capacity. METHODS: We analyzed a prospective cohort of acute right middle cerebral artery ischemic stroke patients. First, we calculated the correlation between NIHSS scores and lesion volume and analyzed the partial correlation of neglect. Then, we applied different modifications in the neglect scoring rules and investigated how they interfered with lesion volume predictive capacity. RESULTS: A total of 162 ischemic stroke patients were included, 108 with neglect and 54 without. The correlation between lesion volume and NIHSS was lower in patients with neglect (r = 0.540 vs. r = 0.219, p = 0.004) and neglect was a statistically significant covariate in the partial correlation analysis between NIHSS and lesion volume (p = 0.017). With the neglect score tripled and with the duplication or triplication of all neglect modalities, the correlation was significantly higher than with the standard NIHSS (p = 0.043, p = 0.005, p = 0.001, respectively). With these modifications, neglect was no longer a significant covariable in the partial correlation between lesion volume and NIHSS. CONCLUSION: A modification of NIHSS neglect scoring might improve the scale's capacity to predict lesion volume.

Stroke and Recent Myocardial Infarction, Reduced Left Ventricular Ejection Fraction, Left Ventricular Thrombus, and Wall Motion Abnormalities.

PURPOSE OF REVIEW: To review the evidence regarding stroke and recent myocardial infarction (MI), reduced left ventricular ejection fraction, left ventricular thrombus (LVT), and wall motion abnormalities (WMA). RECENT FINDINGS: The risk of ischemic stroke associated with acute MI has been greatly reduced with reperfusion treatments that improved myocardium salvage. Acute ischemic stroke is an uncommon complication of diagnostic coronary angiography and percutaneous coronary intervention. For established LVT, anticoagulation is superior to antiplatelet medications to reduce the risk of ischemic stroke. The duration of anticoagulation should be at least 3 to 6 months. Direct oral anticoagulants have been used off-label in this context. In patients with low ejection fraction or WMA, there is no evidence that anticoagulation is superior to antiplatelet treatment in preventing ischemic stroke. In patients with ischemic stroke and recent MI (< 3 months), type of MI (STEMI or NSTEMI), timing, and location should be considered when deciding whether intravenous thrombolysis should be used for stroke treatment. Mechanical thrombectomy should be considered as a therapeutic alternative to intravenous thrombolysis in patients with acute ischemic stroke due to large-vessel occlusion and recent MI. Most guidelines regarding prevention of ischemic stroke in patients with these cardiac causes of stroke are derived from expert opinion. There is a need for high quality evidence to support stroke prevention treatments in these patients.

Deep Learning-Based Extraction of Biomarkers for the Prediction of the Functional Outcome of Ischemic Stroke Patients.

Accurately predicting functional outcomes in stroke patients remains challenging yet clinically relevant. While brain CTs provide prognostic information, their practical value for outcome prediction is unclear. We analyzed a multi-center cohort of 743 ischemic stroke patients (<72 h onset), including their admission brain NCCT and CTA scans as well as their clinical data. Our goal was to predict the patients' future functional outcome, measured by the 3-month post-stroke modified Rankin Scale (mRS), dichotomized into good (mRS ≤ 2) and poor (mRS > 2). To this end, we developed deep learning models to predict the outcome from CT data only, and models that incorporate other patient variables. Three deep learning architectures were tested in the image-only prediction, achieving 0.779 ± 0.005 AUC. In addition, we created a model fusing imaging and tabular data by feeding the output of a deep learning model trained to detect occlusions on CT angiograms into our prediction framework, which achieved an AUC of 0.806 ± 0.082. These findings highlight how further refinement of prognostic models incorporating both image biomarkers and clinical data could enable more accurate outcome prediction for ischemic stroke patients.

Sensitivity and Accuracy of Doppler Ultrasound compared to CT Angiography for the Diagnosis of Carotid Webs: Systematic Review.

INTRODUCTION: Carotid webs (CaW) are increasingly recognized as a cause of cryptogenic acute ischemic stroke (AIS). Due to the risk of recurrent ischemic stroke associated with CaW, it is important to identify them. Although several studies report digital subtraction angiography (DSA) and computerized tomography angiography (CTA) to be better at diagnosing CaW than Doppler ultrasound (DUS), it remains to be defined which is the best radiological method to diagnose CaW. Our aim was to evaluate sensitivity and accuracy of DUS compared to CTA for CaW diagnosis. METHODS: We searched PUBMED and EMBASE databases from inception through August 2022. We included studies with patients with CaW diagnosed by DUS and/or CTA, in which both methods were used in each patient. Demographic characteristics, diagnostic reports of each method and histology reports were collected. Descriptive analysis and sensitivity and accuracy estimates were made to evaluate DUS compared to CTA. RESULTS: We included 27 articles in the systematic review (121 patients with CaW). DUS identified 94 patients with CaW and CTA 116 patients. DUS missed diagnosis in 22.3% (27 patients) and CTA did not identified CaW detected by DUS in 4.13% (5 patients). Accuracy rate between DUS and CTA was 73.6% (95% CI 64.8 to 81.2%). Sensitivity of DUS to diagnose CaW compared to CTA was 76.7% (95% CI 68.0 to 84.1%). Most common misdiagnosis with DUS were normal exam (44.4%), atherosclerosis (22.2%) and dissection (22.2%). CONCLUSION: The sensitivity and accuracy of DUS to diagnosis of CaW were moderate. It might detect CaW in some cases in which it was not identified by CTA. Increase recognition of CaW and specific ultrasound protocols may enhance diagnosis of CaW by DUS.

Ultrasonographic Vasospasm and Outcome of Posterior Reversible Encephalopathy and Cerebral Vasoconstriction Syndromes.

PURPOSE: Posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS) are often complicated by vasospasm and ischemia. Monitoring with transcranial color-coded Doppler (TCCD) could be useful, but its role is not established. We studied the incidence of ultrasonographic vasospasm (uVSP) in PRES/RCVS and its relationship with ischemic lesions and clinical outcome. MATERIALS AND METHODS: We conducted a multicenter retrospective study of all patients with PRES/RCVS from 2008 to 2020 who underwent TCCD and magnetic resonance imaging (MRI). TCCD exams were analyzed for uVSP. Diffusion-weighted MRI was analyzed for positive lesions (DWI-positive). Functional outcome was assessed by modified Rankin scale (mRS) at 90 days. The associations with outcomes were determined by logistic regression. RESULTS: We included 80 patients (mean age of 46 (standard deviation, 17) years; 66% females; 41 with PRES, 28 with RCVS and 11 with overlap phenotype). uVSP was detected in 25 (31%) patients. DWI-positive lesions were more often detected in uVSP-positive than uVSP-negative patients (36% vs. 15%; adjusted odds ratio [aOR] 4.05 [95% CI 1.06 - 15.5], P=0.04). DWI-positive lesions were independently associated with worse functional prognosis (mRS 2-6, 43% vs. 10%; aOR, 10 [95% CI 2.6 - 43], P<0.01). Having additional uVSP further increased the odds of a worse outcome (P interaction=0.03). CONCLUSION: Ultrasonographic vasospasm was detected in a third of patients with PRES/RCVS and was associated with brain ischemic lesions. TCCD bedside monitoring can help to stratify patients at risk for cerebral ischemia, a strong predictor of functional outcome.

Diagnosis of atrial fibrillation in young patients with ischemic stroke: A systematic review and meta-analysis.

INTRODUCTION: The recommended cardiac rhythm evaluation to determine the etiology of ischemic stroke (IS) is similar in all patients regardless of their age and includes an electrocardiogram and at least a 24-hour heart rhythm monitoring. However, it is known that the main causes of IS vary according to patients' age. There is a higher preponderance of arterial dissections and patent foramen ovale in younger patients, while atrial fibrillation (AF) is more common in older patients. AIMS: To determine the proportion of AF in young IS reported in the literature and determine if young IS patients found to have AF had known structural cardiac pathology. METHODS: Systematic review of the literature searching PubMed and Embase for articles published since their inception to August 2020. Inclusion criteria were studies including at least 10 patients, aged 14-50 years-old, clinical or radiological diagnosis of IS and quantification of patients found to have AF. We conducted a meta-analysis using a random-effects model and calculated pooled proportions with 95% confidence intervals. RESULTS: 8331 articles were screened, 154 were selected for full-text review. 43 studies were included in our final analysis (902800 patients). The proportion of AF in young IS overall was 3.1% [95%CI 2.4-3.7], I2 93.88%. Sub-analysis revealed a proportion of AF of 3.8% [95% CI 0.3-7.3] in lower-middle-income economies, versus 5.4% [95% CI 3-7.9] in upper-middle-income economies, and 2.2% [95% CI 1.6-2.8] in high-income economies. Only 3 studies mentioned the proportion of patients with AF that had structural cardiac pathology. CONCLUSION: The proportion of AF in young IS was low. More studies are needed to better understand if young IS patients diagnosed with AF had a priori known structural cardiac pathology that could increase the probability of finding AF. This could lead to a reevaluation of the need for 24 hours cardiac rhythm evaluation in young patients without cardiac pathology.

Update on Biomarkers Associated with Large-Artery Atherosclerosis Stroke.

Intracranial and extracranial large-artery atherosclerosis (LAA) are a main cause of ischemic stroke. Biomarkers may aid in the diagnosis of LAA and help to stratify patients' risk of stroke. We performed a narrative review of the literature, mainly published in the last five years, with the aim of identifying biomarkers associated either with intracranial or extracranial LAA in humans. Several potential biomarkers of LAA, mainly related to lipidic pathways and inflammation, have been studied. Diagnostic biomarkers of LAA were evaluated by measuring biomarkers levels in patients with LAA stroke and other stroke etiologies. Some biomarkers were associated with the functional prognosis of LAA stroke patients. Increased levels of IL-6 and sLOX-1 were associated with a risk of progression of carotid atherosclerotic disease. Findings support the notion that the immune system plays a central role in the pathogenesis of LAA. Overall, in most studies, results were not externally validated. In the future, biomarkers could be useful for the selection of patients for clinical trials. To adopt these biomarkers in clinical practice, we will need robust multicentric studies proving their reproducibility and a clear practical applicability for their use.

Follow-Up by Transcranial Doppler After Rupture of a Giant Intracranial Aneurysm.

Giant intracranial aneurysms (GIA) are rare and manifest primarily through subarachnoid hemorrhage (SAH), cerebral ischemia, or progressive symptoms of mass effect. Transcranial Doppler (TCD) can be used to monitor cerebral vasospasm after treatment of intracranial aneurysm allowing the adjustment of therapeutics and avoiding complications. The authors present a clinical case of a patient with a ruptured intracranial giant aneurysm in which TCD was essential to monitor vasospasm and intracranial hypertension (IH). A 53-year-old male was admitted due to a sudden headache and impaired consciousness, left hemiparesis, and dysarthria. Cerebral CT scan and CT angiography at admission showed a giant aneurysm of the right middle cerebral artery (MCA) with extensive and diffuse intraventricular SAH of Fisher grade IV and Hunt and Hess grade 4. Clipping, placement of an intracranial pressure sensor, and external ventricular drain (EVD) were performed on the same day, with difficulty in preserving the M2 branch and complicated by postoperative extensive right MCA ischemia. On day three of hospitalization, TCD revealed an increased pulsatility index (>1.5) with clinical deterioration leading to re-intervention for a decompressive craniectomy. On day six, a TCD follow-up was performed to monitor blood flow complications, and particularly vasospasm, showing a severe increase in middle blood flow velocity (MBFV) in the right MCA of 205 cm/s and Lindegaard Index > 6. Daily surveillance by TCD was maintained to guide clinical management since the attempt to withdraw the EVD led to clinical deterioration with subsequent worsening of vasospasm. Improvement occurred after surgery as ventriculoperitoneal shunt insertion was performed. TCD had a major role in the clinical orientation of SAH as well as in intracranial pressure management and was decisive to establish long-term treatment.

Time perception changes in stroke patients: A systematic literature review.

Introduction: Time perception comprises the subjective experience of passing of time and of the duration of an event. Although already described in some neurological and psychiatric conditions, there is a paucity of details regarding this neurocognitive change in stroke patients. We aimed to describe time perception dysfunction in stroke patient. Methods: We performed a systematic review of the literature in Pubmed, PsycInfo and EMBASE including manuscripts from their inception until December 2020. We collected data regarding the type of time perception that was detected, type of stroke, most common location of lesions, evaluation tests that were used and time of evaluation after stroke onset. Results: A total of 27 manuscripts were selected, concerning a total of 418 patients (n = 253 male; 60.5%). Most manuscripts (n = 21) evaluated patients with ischaemic lesions (n = 407; 97.4%). The majority referred to evaluations between 2 months and seven years after stroke. Underestimation in temporal evaluation in sub- and supra-second was the most common dysfunction (n = 165; 41.7%). Overestimation of time (n = 116; 27.8%) and impaired time interval comparison (n = 88; 22.2%) were also found. Most patients had right hemisphere lesions (n = 219 patients; 52.4%). Common reported lesion locations included the thalamus, insula, basal ganglia, dorsolateral prefrontal cortex, parietal cortex including supramarginal, angular gyrus and right inferior parietal cortex and cerebellum. Conclusion: There are multiple stroke locations associated with time perception dysfunction, which highlights the complex system involved in time perception. There is still scarce knowledge about specific time perception deficits after stroke. Most studies rely in psychometric analysis without clear clinical and functional translation, namely regarding impact on daily activities.

Male Reproductive Health - study of a sperm donor population.

OBJECTIVE: Every individual has the right to a safe and satisfactory sex and reproductive life. Therefore, several countries have made efforts to make Reproductive Health resources available to their populations. However, few results have been published regarding the policies implemented in Portugal. This study looked into the reproductive health status of the Portuguese male population. METHODS: Sperm donor candidates from the Portuguese Public Gamete Bank registered between 2011 and 2018 were included in the study. Spermogram findings were evaluated with respect to sociodemographic and risk factors. RESULTS: This is the first study performed in this population. We found that sperm quality has decreased throughout the last nine years, and that spermatozoa progressive motility is inversely correlated with the body mass index. An association between drug use and decreased sperm pH was also found. CONCLUSIONS: Changes in sperm quality have important consequences in male fertility. Most of the identified causes of decreased sperm quality are modifiable factors and should therefore be addressed since an early age.

European Stroke Organisation - European Society for Minimally Invasive Neurological Therapy expedited recommendation on indication for intravenous thrombolysis before mechanical thrombectomy in patients with acute ischaemic stroke and anterior circulation large vessel occlusion.

Six randomized controlled clinical trials have assessed whether mechanical thrombectomy (MT) alone is non-inferior to intravenous thrombolysis (IVT) plus MT within 4.5 hours of symptom onset in patients with anterior circulation large vessel occlusion (LVO) ischaemic stroke and no contraindication to IVT. An expedited recommendation process was initiated by the European Stroke Organisation (ESO) and conducted with the European Society of Minimally Invasive Neurological Therapy (ESMINT) according to ESO standard operating procedure based on the GRADE system. We identified two relevant Population, Intervention, Comparator, Outcome (PICO) questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence and wrote evidence-based recommendations. Expert opinion was provided if insufficient evidence was available to provide recommendations based on the GRADE approach. For stroke patients with anterior circulation LVO directly admitted to a MT-capable centre ('mothership') within 4.5 hours of symptom onset and eligible for both treatments, we recommend IVT plus MT over MT alone (moderate evidence, strong recommendation). MT should not prevent the initiation of IVT, nor should IVT delay MT. In stroke patients with anterior circulation LVO admitted to a centre without MT facilities and eligible for IVT ≤4.5 hrs and MT, we recommend IVT followed by rapid transfer to a MT capable-centre ('drip-and-ship') in preference to omitting IVT (low evidence, strong recommendation). Expert consensus statements on ischaemic stroke on awakening from sleep are also provided. Patients with anterior circulation LVO stroke should receive IVT in addition to MT if they have no contraindications to either treatment.

Obesity and the Risk of Cryptogenic Ischemic Stroke in Young Adults.

OBJECTIVES: We examined the association between obesity and early-onset cryptogenic ischemic stroke (CIS) and whether fat distribution or sex altered this association. MATERIALS AND METHODS: This prospective, multi-center, case-control study included 345 patients, aged 18-49 years, with first-ever, acute CIS. The control group included 345 age- and sex-matched stroke-free individuals. We measured height, weight, waist circumference, and hip circumference. Obesity metrics analyzed included body mass index (BMI), waist-to-hip ratio (WHR), waist-to-stature ratio (WSR), and a body shape index (ABSI). Models were adjusted for age, level of education, vascular risk factors, and migraine with aura. RESULTS: After adjusting for demographics, vascular risk factors, and migraine with aura, the highest tertile of WHR was associated with CIS (OR for highest versus lowest WHR tertile 2.81, 95%CI 1.43-5.51; P=0.003). In sex-specific analyses, WHR tertiles were not associated with CIS. However, using WHO WHR cutoff values (>0.85 for women, >0.90 for men), abdominally obese women were at increased risk of CIS (OR 2.09, 95%CI 1.02-4.27; P=0.045). After adjusting for confounders, WC, BMI, WSR, or ABSI were not associated with CIS. CONCLUSIONS: Abdominal obesity measured with WHR was an independent risk factor for CIS in young adults after rigorous adjustment for concomitant risk factors.

European Stroke Organisation (ESO)-European Society for Minimally Invasive Neurological Therapy (ESMINT) expedited recommendation on indication for intravenous thrombolysis before mechanical thrombectomy in patients with acute ischemic stroke and anterior circulation large vessel occlusion.

Six randomized controlled clinical trials have assessed whether mechanical thrombectomy (MT) alone is non-inferior to intravenous thrombolysis (IVT) plus MT within 4.5 hours of symptom onset in patients with anterior circulation large vessel occlusion (LVO) ischemic stroke and no contraindication to IVT. An expedited recommendation process was initiated by the European Stroke Organisation (ESO) and conducted with the European Society of Minimally Invasive Neurological Therapy (ESMINT) according to ESO standard operating procedure based on the GRADE system. We identified two relevant Population, Intervention, Comparator, Outcome (PICO) questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and wrote evidence-based recommendations. Expert opinion was provided if insufficient evidence was available to provide recommendations based on the GRADE approach.For stroke patients with anterior circulation LVO directly admitted to a MT-capable center ('mothership') within 4.5 hours of symptom onset and eligible for both treatments, we recommend IVT plus MT over MT alone (moderate evidence, strong recommendation). MT should not prevent the initiation of IVT, nor should IVT delay MT. In stroke patients with anterior circulation LVO admitted to a center without MT facilities and eligible for IVT ≤4.5 hours and MT, we recommend IVT followed by rapid transfer to a MT capable-center ('drip-and-ship') in preference to omitting IVT (low evidence, strong recommendation). Expert consensus statements on ischemic stroke on awakening from sleep are also provided. Patients with anterior circulation LVO stroke should receive IVT in addition to MT if they have no contraindications to either treatment.

Risk of intracranial haemorrhage and ischaemic stroke after convexity subarachnoid haemorrhage in cerebral amyloid angiopathy: international individual patient data pooled analysis.

OBJECTIVE: To investigate the frequency, time-course and predictors of intracerebral haemorrhage (ICH), recurrent convexity subarachnoid haemorrhage (cSAH), and ischemic stroke after cSAH associated with cerebral amyloid angiopathy (CAA). METHODS: We performed a systematic review and international individual patient-data pooled analysis in patients with cSAH associated with probable or possible CAA diagnosed on baseline MRI using the modified Boston criteria. We used Cox proportional hazards models with a frailty term to account for between-cohort differences. RESULTS: We included 190 patients (mean age 74.5 years; 45.3% female) from 13 centers with 385 patient-years of follow-up (median 1.4 years). The risks of each outcome (per patient-year) were: ICH 13.2% (95% CI 9.9-17.4); recurrent cSAH 11.1% (95% CI 7.9-15.2); combined ICH, cSAH, or both 21.4% (95% CI 16.7-26.9), ischemic stroke 5.1% (95% CI 3.1-8) and death 8.3% (95% CI 5.6-11.8). In multivariable models, there is evidence that patients with probable CAA (compared to possible CAA) had a higher risk of ICH (HR 8.45, 95% CI 1.13-75.5, p = 0.02) and cSAH (HR 3.66, 95% CI 0.84-15.9, p = 0.08) but not ischemic stroke (HR 0.56, 95% CI 0.17-1.82, p = 0.33) or mortality (HR 0.54, 95% CI 0.16-1.78, p = 0.31). CONCLUSIONS: Patients with cSAH associated with probable or possible CAA have high risk of future ICH and recurrent cSAH. Convexity SAH associated with probable (vs possible) CAA is associated with increased risk of ICH, and cSAH but not ischemic stroke. Our data provide precise risk estimates for key vascular events after cSAH associated with CAA which can inform management decisions.