INTRODUCTION:Glomerular hyperfiltration has previously been associated with cardiovascular events and mortality but has scarcely been investigated in patients with stroke. PATIENTS AND METHODS:We used pooled data from an individual patient data meta-analysis of prospective, cohort studies of stroke or TIA populations. For this analysis, we included participants from study sites that collected estimated glomerular filtration rate (eGFR) at stroke presentation. Using Cox proportional hazards regression, we investigated the risk of death, any stroke and vascular death according to glomerular hyperfiltration, defined as having an eGFR greater than the age- and sex-adjusted 95th percentile. We also investigated these outcomes according to eGFR as a continuous variable, modelled using fractional polynomials. RESULTS:A total of 11,175 patients (mean age 70.7 years, 42% female) were included in the analysis, 554 (4.9%) with hyperfiltration. Compared to the normofiltration group (absence of hyperfiltration and eGFR ≥ 60 mL/min/1.73 m2), the hyperfiltration group had a higher rate of all-cause death, 147 per 1000 person-years (95% CI, 119-180) vs 61 (95% CI, 57-66). Compared to normofiltration, hyperfiltration was independently associated with the risk of death from any cause (adjusted hazard ratio [HR] 1.76; 95% CI, 1.46-2.11; P < .001) and the risk of vascular death (adjusted HR 1.68; 95% CI, 1.29-2.17; P < .001). There were non-linear associations of eGFR with risk of death and vascular death, with increasing risk at both low and high eGFR (Pnon-linearity < .001 for both). DISCUSSION AND CONCLUSION:Glomerular hyperfiltration was associated with a 76% increased risk of death and a 68% increased risk of vascular death in multivariable models adjusted for age, sex and comorbidities. Glomerular hyperfiltration may be associated with adverse health outcomes, specifically in patients with ischaemic stroke. Further research is needed to confirm these findings.
Abstract Background and aims Multiple randomized control trials have shown that thrombectomy for ischemic stroke resulting from large vessel occlusion (LVO) reduces disability and is cost effective. There remains uncertainty whether thrombectomy for patients with pre-stroke disability (modified Rankin Score/mRS3-4) is similarly effective, as prior meta-analysis (n=14) included cases of mRS2 among those classified as pre-stroke disability. This study aimed to meta-analyse the outcomes of thrombectomy for LVO in those with moderate disability (mRS3-4). Methods We searched Pubmed, Medline and Clinicaltrials.gov using search terms "stroke", "large vessel occlusion", "disability", "prestroke disability", or "pre-stroke disability" on 4/1/2026. From 384 studies, we included those with >90 patients or if there were extractable data on cases with mRS3-4. Analyses were conducted in R using the meta and metafor packages. Results Of 27 studies, two duplicates were excluded. In the remaining 25 studies, 5084/60199 patients with a pre-stroke disability (10.6%, 95% CI 7.8-13.7, I2=99.3%) received thrombectomy. Mean age was 81.0±2.8years. The majority were female 64.9% (95% CI 61.8-67.9%, I2=97.2%). Return to baseline occurred in 27.3% (95% CI 23.2-31.5%, I2=98.9%) and symptomatic intracerebral hemorrhage occurred in 6.5% (95% CI 5.5-7.7%, I2=94.8%). Mortality was 39.5% (95% CI 34.0-45.1%, I2=99.4%). Conclusions The proportion of patients with pre-stroke disability treated by thrombectomy in LVO registries remains low while a modest proportion of the patients returned to baseline following thrombectomy. Surprisingly a large proportion of patients in registries were female, reversing trends seen previously. The high heterogeneity (I2) suggests a large variation in results, and further work in the form of a trial is needed. Conflict of interest Jason Vuong: nothing to disclose, Shaloo Singhal: nothing to disclose, Michael Valente: nothing to disclose, Angelos Sharobeam: nothing to disclose, Lubna Shakhatreh: nothing to disclose, Andy Lim: nothing to disclose, Peter Mitchell: nothing to disclose, Bernard Yan: nothing to disclose, Henry Ma: nothing to disclose, Thanh Phan: nothing to disclose.
BACKGROUND AND OBJECTIVES:Enlarged perivascular spaces (EPVSs) in the basal ganglia (BG-EPVS) are an important marker of cerebral small vessel disease (cSVD), and EPVS in the centrum semiovale (CSO-EPVS) are part of the diagnostic criteria for cerebral amyloid angiopathy. We aimed to investigate associations of EPVS with reduced estimated glomerular filtration rate (eGFR) and glomerular hyperfiltration (higher than normal eGFR), which have scarcely been studied previously. METHODS:In this cross-sectional study, we used pooled individual patient data from the Microbleeds International Collaborative Network which includes patients with ischemic stroke or transient ischemic attack. We investigated associations of impaired kidney function, defined as an eGFR of 30-60 or <30 mL/minute/1.73 m2, and glomerular hyperfiltration, defined as eGFR above the age-adjusted and sex-adjusted 95th centile, with BG-EPVS and CSO-EPVS severity. EPVS were rated according to a validated 5-point ordinal scale, and combined cSVD burden was rated using a validated 5-point ordinal scale with 1 point assigned for the presence of each of the following: severe white matter hyperintensities, ≥1 cerebral microbleed, ≥1 lacune, and BG-EPVS ≥11. Normal glomerular filtration was defined as eGFR ≥60 without hyperfiltration. We used multivariable ordinal logistic regression models to estimate risk of increased EPVS and cSVD burden severity adjusted for age, sex, and comorbidities. RESULTS:Seven thousand two hundred fifty-four patients (mean age 71 ± 13 years, 43% female) were included in the analysis, 357 with glomerular hyperfiltration, 1,692 with eGFR 30-60, and 256 with eGFR <30. Compared with normal glomerular filtration, hyperfiltration was independently associated with BG-EPVS (adjusted odds ratio [aOR] 1.38, 95% CI 1.11-1.70, p < 0.001) and CSO-EPVS (aOR 1.34, 95% CI 1.08-1.64, p = 0.011). Associations of eGFR 30-60 and eGFR <30 with EPVS were not statistically significant. Compared with normal glomerular filtration, eGFR <30 (aOR 1.27, 95% CI 1.03-1.57) was independently associated with increased cSVD burden, but eGFR 30-60 (aOR 1.06, 95% CI 0.95-1.20) and hyperfiltration (aOR 1.15, 95% CI 0.98-1.34) were not. DISCUSSION:Glomerular hyperfiltration was independently associated with EPVS severity, in both the basal ganglia and centrum semiovale. eGFR <30 was independently associated with total cSVD burden. A key limitation was a lack of repeated eGFR measurements.
Background and objectives The most common cause of convexity subarachnoid hemorrhage (cSAH) in younger patients (younger than 60 years) is reversible cerebral vasoconstriction syndrome (RCVS). Evidence on the long-term outcomes of future vascular events and functional outcome after cSAH due to RCVS is limited. We aimed to assess the rates and baseline predictors of our primary outcomes (cSAH, intracerebral hemorrhage (ICH), and ischemic stroke), functional outcome, and mortality after cSAH attributed to RCVS. Methods Individual patient data pooled analysis in patients with cSAH attributed to RCVS. A systematic literature search was conducted in PubMed and EMBASE. Two independent reviewers screened studies and extracted data. Quality assessment was assessed using the Newcastle-Ottawa Scale. Early events during the accepted time frame of an RCVS episode (<3 months) were classified as progression rather than recurrence. Follow-up was truncated at 5 years. Primary outcomes were recurrent cSAH, ICH, and ischemic stroke. Secondary outcomes were mortality and functional status measured by modified Rankin Score (mRS). Results We identified 21 eligible cohorts finally including 138 patients from 9 collaborative centers, which provided individual patient data. The mean age was 49.3 +/- 12.1 years, and 110 (79.7%) were female. During a mean follow-up of 1.8 years, annual rates were cSAH recurrence 0.81% (95% CI 0.1-2.91), ICH 0.81% (95% CI 0.1-2.91), and ischemic stroke 0.81% (95% CI 0.1-2.91). Progression during the initial episode (shortly after admission) occurred in 10 patients for cSAH, 2 for ICH, and 8 for ischemic stroke, respectively. Of 106 patients (76.8%) with available outcome data, 100 (94.3%) achieve a mRS of <= 1 at follow-up, indicating no significant disability. Two patients died (annual rate 0.5%, 95% CI 0.09-2.9): one within 10 days and the other within 2 months of the cSAH. Discussion Our data suggest a favorable prognosis for most patients after RCVS-associated cSAH with low rates of recurrent events and a high proportion achieving functional independence. Major limitations include retrospective data collection and potential selection bias from centers providing individual patient data. Nevertheless, these findings provide prognostic information to inform clinical practice.
BACKGROUND:Patients with chronic kidney disease are at increased risk of stroke and frequently have cerebral microbleeds. Whether such patients also encounter an increased risk of recurrent stroke has not been firmly established. We aimed to determine whether impaired kidney function is associated with the risk of recurrent stroke, and microbleed presence, distribution and severity. METHODS:We used pooled data from the Microbleeds International Collaborate Network to investigate associations of impaired kidney function, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Our primary outcome was a composite of recurrent ischaemic stroke (IS) and intracranial haemorrhage (ICrH). Secondary outcomes included: (1) individual components of the primary outcome; (2) modification of the primary outcome by microbleed presence or anticoagulant use and (3) microbleed presence, distribution and severity. RESULTS:11 175 patients (mean age 70.7±12.6, 42% female) were included, of which 2815 (25.2%) had impaired kidney function. Compared with eGFR ≥60, eGFR <60 was associated with a higher risk of the primary outcome (adjusted HR, aHR 1.33 (95% CI 1.14 to 1.56), p<0.001) and higher rates of the recurrent IS (aHR 1.33 (95% CI 1.12 to 1.58)). Reduced eGFR was not associated with ICrH risk (aHR 1.07 (95% CI 0.70 to 1.60)). eGFR was also associated with microbleed presence (adjusted OR, aOR 1.14 (95% CI 1.03 to 1.26)) and severity (aOR 1.17 (95% CI 1.06 to 1.29)). Compared with having no microbleeds, eGFR was lower in those with strictly lobar microbleeds (adjusted mean difference (aMD) -2.10 mL/min/1.73 cm2 (95% CI -3.39 to -0.81)) and mixed microbleeds (aMD -2.42 (95% CI -3.70 to -1.15)), but not strictly deep microbleeds (aMD -0.67 (95% CI -1.85 to 0.51)). CONCLUSIONS:In patients with IS or transient ischaemic attack, impaired kidney function was associated with a higher risk of recurrent stroke and higher microbleeds burden, compared with those with normal kidney function. Further research is needed to investigate potential additional measures for secondary prevention in this high-risk group.
Introduction: Following posterior cerebral artery stroke, infarcts causing quadrantanopia are thought to be smaller than those causing homonymous hemianopia. We investigated whether these two presentations were different due to the varying involvement of the striate, extrastriate cortex, or geniculocalcarine tract. METHODS:Patients with unilateral posterior cerebral artery infarcts on magnetic resonance imaging and visual field defects, as identified by automated visual field perimetry, were included. Infarcts were manually segmented and registered to a standard brain template to facilitate comparison. Infarct volume and infarct involvement with geniculocalcarine fiber tracts were calculated in patients with hemianopia and quadrantanopia. RESULTS:There were twenty-two patients: 15 patients with homonymous hemianopia (median age 68 [interquartile range, 55-76 years old]) and 7 with superior quadrantanopia (median age 40 [interquartile range, 30-56 years old]). Infarct volume significantly differed between the two groups: hemianopia 34.6 mL (interquartile range, 21.6-56.3 mL) versus superior quadrantanopia 15.5 mL (interquartile range, 7.2-24.1 mL), p = 0.026. There was significantly greater involvement of infarct with the geniculocalcarine tracts in the hemianopia group, 5.7 mL (interquartile range, 2.3-8.2 mL) than the superior quadrantanopia group, 2.0 mL (interquartile range, 1.2-2.7 mL), p = 0.042. Infarct involvement with cuneus and the calcarine cortex also significantly differed between the two groups (p ≤ 0.01). CONCLUSION:In posterior cerebral artery infarction, sparing of the superior calcarine cortex, cuneus, and superior paraventricular geniculocalcarine tract differentiated superior quadrantanopia from homonymous hemianopia. .
Background and aimRapid outpatient evaluation and treatment of TIA in structured clinics have been shown to reduce stroke recurrence. It is unclear whether short-term downtrends in TIA incidence and admissions have had enduring impact on TIA clinic activity. This study aims to measure the impact of the pandemic on hospitals with rapid TIA clinics.MethodsRelevant services were identified by literature search and contacted. Three years of monthly data were requested – a baseline pre-COVID period (April 2018 to March 2020) and an intra-COVID period (April 2020 to March 2021). TIA presentations, ischemic stroke presentations, and reperfusion trends inclusive of IV thrombolysis (IVT) and endovascular thrombectomy (EVT) were recorded. Pandemic impact was measured with interrupted time series analysis, a segmented regression approach to test an effect of an intervention on a time-dependent outcome using a defined impact model.ResultsSix centers provided data for a total of 6,231 TIA and 13,191 ischemic stroke presentations from Australia (52.1%), Canada (35.0%), Italy (7.6%), and England (5.4%). TIA clinic volumes remained constant during the pandemic (2.9, 95% CI –1.8 to 7.6, p = 0.24), as did ischemic stroke (2.9, 95% CI –7.8 to 1.9, p = 0.25), IVT (−14.3, 95% CI −36.7, 6.1, p < 0.01), and EVT (0, 95% CI –16.9 to 16.9, p = 0.98) counts. Proportion of ischemic strokes requiring IVT decreased from 13.2 to 11.4% (p < 0.05), but those requiring EVT did not change (16.0 to 16.7%, p = 0.33).ConclusionThis suggests that the pandemic has not had an enduring effect on TIA clinic or stroke service activity for these centers. Furthermore, the disproportionate decrease in IVT suggests that patients may be presenting outside the IVT window during the pandemic – delays in seeking treatment in this group could be the target for public health intervention.
Objectives This study aims to investigate the cost incurred by people travelling to the neurology outpatient clinic of a large metropolitan hospital. As outpatients are a substantial portion of a hospital’s demographic, we aimed to understand the patient experience of various commuters.Methods We conducted an observational study collecting demographic details and travel information for how people attended the neurology clinic of Monash Medical Centre. Statistical analysis was performed using R. 165 participants were randomly selected and interviewed in-person. Data were collected via an anonymous questionnaire. The study was approved by the Monash Health Human Ethics Research Committee.Results 155 responses were included in the analysis. Patients paid an average of $A16.64 to travel to Monash Medical Centre. Drivers paid on average $A16.70 and those taking public transport paid on average $A9.64, with the maximum cost overall being $A120.00. For patients driving to hospital, parking accounted for 60% of their travel costs. The average to Monash Medical centre was 20.82 km with the maximum being 190.88 km. Distance from hospital was correlated with a higher cost of travel (p<0.001, Spearman’s rank correlation coefficient=0.48). There was also an inverse association between distance from hospital and socioeconomic status (p<0.001, Spearman’s rank correlation coefficient=−0.26).Conclusion Travelling to hospital can be a costly endeavour. Driving is the most popular form of transport, but a large portion of the cost involved is hospital parking. Further research should be conducted at other tertiary centres with larger samples.
ImportanceDual antiplatelet therapy (DAPT) appears to be an effective treatment option for minor (nondisabling) acute ischemic stroke. This conclusion is based on trials that include both transient ischemic attack (TIA) and minor stroke; however, these 2 conditions may differ.ObjectiveTo compare DAPT regimens specifically for minor stroke.Data SourcesPubMed was searched for randomized clinical trials published up to November 4, 2023. Search terms strategy included TIA, transient ischemic attack, minor stroke, or moderate stroke, with the filter randomized controlled trial. Unpublished data on minor stroke were sourced from authors and/or institutions.Study SelectionTrials testing DAPT within the first 24 hours of a minor stroke (defined as a National Institutes of Health Stroke Scale score ≤5) were included by consensus. Of 1508 studies screened, 6 (0.3%) initially met inclusion criteria and were reviewed.Data Extraction and SynthesisThe study was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines by multiple observers. Bayesian fixed-effect network meta-analysis was conducted. Secondary analysis performed for high-risk TIA alone.Main Outcomes and MeasuresTreatments were ranked using a probability measure called surface under the cumulative rank curve (SUCRA). The primary outcome was subsequent ischemic stroke at 90 days. Secondary outcomes included major hemorrhage, mortality, and hemorrhagic stroke. The number needed to treat (NNT) and number needed to harm (NNH) were obtained.ResultsFive trials were included that described 28 148 patients, of whom 22 203 (78.9%) had a minor stroke. Of these, 13 995 (63.0%) were in DAPT groups and 8208 (37.0%) in aspirin (acetylsalicylic acid) groups. Aspirin and ticagrelor had a 94% probability of being the superior treatment for minor stroke (SUCRA, 0.94) for the primary outcome. Both aspirin and ticagrelor (NNT, 40; 95% CI, 31-64) and aspirin and clopidogrel (NNT, 58; 95% CI, 39-136) were superior to aspirin alone in the prevention of recurrent ischemic stroke at 90 days. Both treatments had higher rates of major hemorrhage than aspirin alone (NNH for aspirin and ticagrelor, 284; 95% CI, 108-1715 vs NNH for aspirin and clopidogrel, 330; 95% CI, 118-3430), but neither had increased risk of hemorrhagic stroke or death. For high-risk TIA, ticagrelor and aspirin had a 60% probability (SUCRA, 0.60) and clopidogrel and aspirin had a 40% probability (SUCRA 0.40) of being a superior treatment; neither was optimum, but both were superior to aspirin alone for the primary outcome.Conclusions and RelevanceThese findings suggest that DAPT with aspirin and ticagrelor has higher probability of being the superior treatment among patients with minor stroke when presence of CYP2C19 loss-of-function alleles has not been excluded. For patients with TIA, the superiority of aspirin and ticagrelor vs aspirin and clopidogrel was not demonstrated.
To study the prevalence of osteoporosis, falls and fractures in adults with ischaemic stroke. Observational cohort study of adults aged ≥ 50 years admitted with ischaemic stroke over a 12-month period were invited to participate in a telephone interview one-year post-stroke to ascertain falls and fracture. A Fracture Risk After Ischaemic Stroke (FRAC-stroke) score was calculated. Of the 1267 patients admitted to the stroke unit between 1 January 2020 and 31 December 2020, 624 had a modified Rankin Score documented. Of these, 316 adults ≥ 50 years had ischaemic stroke and 131 consented to a telephone interview. Mean age was 72.4 ± 10.7 years and 36.6
Background Risk of recurrence after minor ischemic stroke is usually reported with transient ischemic attack. No previous meta‐analysis has focused on minor ischemic stroke alone. The objective was to evaluate the pooled proportion of 90‐day stroke recurrence for minor ischemic stroke, defined as a National Institutes of Health Stroke Scale severity score of ≤5. Methods and Results Published papers found on PubMed from 2000 to January 12, 2021, reference lists of relevant articles, and experts in the field were involved in identifying relevant studies. Randomized controlled trials and observational studies describing minor stroke cohort with reported 90‐day stroke recurrence were selected by 2 independent reviewers. Altogether 14 of 432 (3.2%) studies met inclusion criteria. Multilevel random‐effects meta‐analysis was performed. A total of 6 randomized controlled trials and 8 observational studies totaling 45 462 patients were included. The pooled 90‐day stroke recurrence was 8.6% (95% CI, 6.5–10.7), reducing by 0.60% (95% CI, 0.09–1.1; P =0.02) with each subsequent year of publication. Recurrence was lowest in dual antiplatelet trial arms (6.3%, 95% CI, 4.5–8.0) when compared with non‐dual antiplatelet trial arms (7.2%, 95% CI, 4.7–9.6) and observational studies 10.6% (95% CI, 7.0–14.2). Age, hypertension, diabetes, ischemic heart disease, or known atrial fibrillation had no significant association with outcome. Defining minor stroke with a lower National Institutes of Health Stroke Scale threshold made no difference – score ≤3: 8.6% (95% CI, 6.0–11.1), score ≤4: 8.4% (95% CI, 6.1–10.6), as did excluding studies with n<500%–7.3% (95% CI, 5.5–9.0). Conclusions The risk of recurrence after minor ischemic stroke is declining over time but remains important.
BackgroundWe proposed a Phase I dose escalation trial to assess the safety of allogeneic human amniotic epithelial cells (hAECs) in stroke patients with a view to informing the design for a Phase II trial.MethodsThe design is based on 3 + 3 dose escalation design with additional components for measuring MR signal of efficacy as well as the effect of hAECs (2–8 × 106/kg, i.v.) on preventing immunosuppression after stroke.ResultsEight patients (six males) were recruited within 24 h of ischemic stroke onset and were infused with hAECs. We were able to increase the dose of hAECs to 8 × 106 cells/kg (2 × 106/kg, n = 3; 4 × 106/kg, n = 3; 8 × 106/kg, n = 2). The mean age is 68.0 ± 10.9 (mean ± SD). The frequencies of hypertension and hyperlipidemia were 87.5%, diabetes was 37.5%, atrial fibrillation was 50%, ischemic heart disease was 37.5% and ever-smoker was 25%. Overall, baseline NIHSS was 7.5 ± 3.1, 7.8 ± 7.2 at 24 h, and 4.9 ± 5.4 at 1 week (n = 8). The modified Rankin scale at 90 days was 2.1 ± 1.2. Supplemental oxygen was given in five patients during hAEC infusion. Using pre-defined criteria, two serious adverse events occurred. One patient developed recurrent stroke and another developed pulmonary embolism whilst in rehabilitation. For the last four patients, infusion of hAECs was split across separate infusions on subsequent days to reduce the risk for fluid overload.ConclusionOur Phase I trial demonstrates that a maximal dose of 2 × 106/kg hAECs given intravenously each day over 2 days (a total of 4 × 106/kg) is safe and optimal for use in a Phase II trial.Clinical trial registrationClinicalTrials.gov, identifier ACTRN12618000076279P.