International Journal of Stroke最新文献

Background: Stroke is a leading cause of global mortality and disability, with a disproportionately high burden in low- and middle-income countries. Access to intravenous thrombolysis (IVT) and endovascular treatment (EVT) remains extremely limited.

Aims: We evaluated the spatial distribution and geographic accessibility of stroke centers in India.

Methods: Data on IVT capable (IVT-C) and EVT capable (EVT-C) stroke centers were collected in March 2021 from thrombectomy devices and pharmaceutical industry providers, respectively. Data were collated and geocoded to compare and calculate zonal statistics and state/union territory (UT) summaries using descriptive statistics. Data on population centers were obtained from the Survey of India website. For estimating driving times, we used the Google Distance Matrix API to find the driving distance between each population center and its nearest stroke facility. Subsequently, population coverages were estimated as a proportion of the population having access to stroke centers for each time interval and based on the population projection for the year 2020 and compared across states.

Results: A total of 566 IVT-C stroke centers were spread across 26 states and UTs, of which 361 (63%) were EVT-C. Ten UTs lacked stroke centers. The average stroke centers per million (SCPM) population was 0.41 and 0.26 for IVT-C and EVT-C, respectively. Median distances to the nearest IVT-C and EVT-C centers were 115 km (interquartile range (IQR): 66-175) and 131 km (IQR: 79-198), respectively. Access within 1 h to an IVT-C and an EVT-C center was available to 26.3% and 20.6% of the Indian population, respectively.

Conclusions: Access to stroke care in India is poor, with critical regional disparities as reflected by the low SCPM population, long driving times, and a small population with access within the golden hour. There is an urgent need to establish IVT-C and EVT-C stroke centers in the existing poorly served regions of India to increase access and improve outcomes for stroke patients.

Background: Observational studies have shown that selective serotonin reuptake inhibitors are associated with an increased risk of bone fractures, but the association can be confounded by indication and other sources of systematic bias that can be minimised in randomised controlled trials (RCTs).

Aim: Our aim was to report the rate, site, context, and predictors of fractures after stroke, and whether the fractures modified the effect of fluoxetine on modified Rankin score (mRS) at six months in an individual patient data meta-analysis of 5907 patients enrolled in three RCTs of fluoxetine (20mg for six months) for stroke recovery.

Methods: We classified fractures by treatment allocation, site (and thus likelihood of osteoporosis) and context, then performed multivariable analyses to explore independent predictors of fractures. We explored whether the trend towards a poorer mRS at 6 months was explained by a fracture excess. Risk of bias was assessed using GRADE.

Results: Among 5907 patients randomised at a mean of 6.6 days (SD3.6) post-stroke onset and followed for six months, the number with fractures at 6 months was 93 (3.15%) in the fluoxetine group vs 41 (1.39%) in the control group (difference 1.76%, 95% CI 0.10 to 2.51%). 128 patients with fractures were suitable for further analyses. Of these 102 (80%) were in sites typically affected by osteoporosis; 115 (90%) were associated with falls and one (1%) with a seizure. Independent fracture risk factors were female sex (hazard ratio (HR) 1.96; 95% CI 1.37 to 2.81, p=0.0002), age>70 years (HR 2.30, 95% CI 1.52 to 3.49, p<0.001), previous fractures (HR 0.63 for no previous fractures, 95% CI 0.42 to 0.94, p=0.0227), and randomised treatment (fluoxetine) (HR 2.39; 95% CI 1.64 to 3.49, p<0.001). The common odds ratio for the effect of fluoxetine on mRS at 6 months was unchanged after excluding fracture patients. Risk of bias was high for imprecision.

Conclusion: Fractures were more common in the fluoxetine group but the absolute risk of fractures was small and risk estimates were imprecise. Most fractures occurred with a fall, and in osteoporotic locations. Fractures did not modify the effect of fluoxetine on functional outcome.

background: : Intravenous thrombolysis (IVT) for acute ischemic stroke (AIS) related to underlying intracranial artery dissection (IAD) poses potential risks, including the exacerbation of intramural hematoma and the rupture of the dissected arterial wall. However, the safety of IVT in this specific population remains uncertain.

aims:: This study aimed to assess whether IAD is associated with an increased risk of intracranial hemorrhage (ICH) following IVT and to evaluate its impact on functional outcomes.

methods: : This retrospective matched-pair cohort study used a nationwide inpatient database that includes discharge abstracts and administrative claims data in Japan. We included adult patients with AIS treated with IVT between July 2010 and July 2024. We excluded patients with carotid or vertebral artery dissections due to difficulties distinguishing between intracranial and extracranial involvement, those lacking premorbid/discharge modified Rankin Scale (mRS) data, and those who received intra-arterial thrombolysis. Patients with IAD were matched 1:4 with non-IAD controls based on age, sex, premorbid mRS, endovascular treatment (EVT), and teaching hospital status. We assessed ICH, functional independence at discharge (mRS 0-2), and in-hospital mortality using multivariable logistic regression with generalized estimating equations to account for clustering within matched pairs, adjusting for age, sex, premorbid mRS, body mass index, smoking history, hypertension, diabetes mellitus, atrial fibrillation, coagulopathy, Japan Coma Scale, EVT, and teaching hospital status.

results:: Of 83,139 patients with AIS treated with IVT, 242 (0.3%) had underlying IAD (median age 54 [46-67] years; 34% women). These patients were matched with 968 non-IAD controls. IAD was associated with a higher risk of ICH (odds ratio [OR], 3.18; 95% confidence interval [CI], 1.26-8.06) and a lower likelihood of functional independence at discharge (OR, 0.51; 95% CI, 0.37-0.72), but not with increased in-hospital mortality (OR, 1.09; 95% CI, 0.50-2.38).

conclusions:: Patients with underlying IAD may face an increased risk of ICH and a reduced chance of functional recovery following IVT compared to those without.

Background: The aim of the study was to examine the association between alcohol consumption and stroke in Nigeria and Ghana.

Methods: The study is a multicentre, case-control study. Cases included consenting adults 18 years of age and older with acute stroke and controls were age-and -gender -matched stroke -free adults. Alcohol consumption was self-reported. The participants were classified into three alcohol-drinking status, which included abstainers, former drinkers, and current drinkers. The current drinkers were further classified into different alcohol drinking levels, including infrequent, light, moderate, heavy, and binge drinkers. Conditional logistic regression was used to determine associations between the drinking status and stroke, and the association between the different levels of current alcohol consumption and stroke. Five models were evaluated. Model 1 was unadjusted. Model 2 was adjusted for demographic characteristics. Model 3 included Model 2, lifestyle and psychosocial characteristics. Model 4 included Model 3 and dietary characteristics. Model 5 included Model 4 and metabolic characteristics.

Results: A total of 7368 participants took part in the study. Half were stroke participants, and half were control participants. On the associations between drinking status and stroke, respectively, former drinkers showed no significant association with stroke. However, a significant association was observed between current drinkers and stroke in Models 1 and 2, with an odds ratio of 1.19 (95% CI: 1.04-1.38; p < 0.05) and 1.17 (95% CI: 1.01-1.36; p < 0.05), respectively. Regarding the various levels of current alcohol drinking and their association with stroke, no significant association was observed between light drinking and stroke in Model 5. In contrast, moderate drinkers, binge drinkers, and heavy drinkers showed a persistent and significant association with stroke respectively.

Conclusion: There is a significant association between stroke and current alcohol consumption, especially among heavy, binge, and moderate drinkers.

Background: Hematoma expansion (HE) occurs in one-fourth to one-third of patients with acute intracerebral hemorrhage (ICH) and is associated with worse outcomes. The co-localization of non-contrast computed tomography (NCCT) hypodensity and computed tomography angiography (CTA) spot sign, the so-called Black-&-White (B&W) sign, has been shown to have high predictive accuracy for HE in a single-center cohort. In this analysis, we aimed to validate the predictive accuracy of the B&W sign for HE in a multicenter cohort.

Methods: Acute ICH patients from the multicenter, observational PREDICT study (Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT) were included. Outcomes included HE (⩾6 mL or ⩾33%) and severe HE (⩾12.5 mL or >66%). The association between B&W sign and outcomes was assessed with multivariable regression analyses adjusted for baseline factors.

Results: Three hundred four patients were included, with 106 (34.9%) showing HE. The spot sign was present in 76 (25%) patients, the hypodensity sign in 119 (39.1%), and the B&W sign in 29 (9.5%). In the stratum with positive spot signs, patients with B&W signs experienced more frequent HE (79.3% vs 46.8%, p = 0.008), hematoma absolute growth (19.1 mL (interquartile range (IQR) = 6.4-40) vs 3.2 mL (IQR= 0-23.3), p = 0.018), and hematoma relative growth (92% (IQR = 16-151%) vs 24% (IQR= 0-69%), p = 0.038). There was a strong association between B&W sign and HE (adjusted odds ratio (OR) = 7.83 (95% confidence interval (CI) = 2.93-20.91)) and severe HE (adjusted OR = 5.67 (95% CI = 2.41-13.36)). The B&W sign yielded a positive predictive value of 79.3% (IQR = 61.7-90.1) for HE. Inter-rater agreement was moderate (k = 0.54).

Conclusion: The B&W sign is associated with an increased likelihood of HE and severe HE by approximately eightfold and fivefold, respectively.

Recent clinical trials provide robust evidence of non-inferiority of tenecteplase 0.25 mg/kg over alteplase 0.9 mg/kg in acute ischemic stroke treated within 4.5 h of time last known well. Aggregate data meta-analysis suggests likely superiority of tenecteplase with respect to excellent (modified Rankin Scale 0 or 1) outcomes at 90 days. Less complex single intravenous bolus administration of tenecteplase brings significant logistical benefits compared to alteplase. Real-world implementation data demonstrate reduced door-to-needle and door-to-puncture times, and potentially improved clinical outcomes. Avoiding the need for infusion pumps and monitoring reduces resource requirements and facilitates inter-hospital transfer. Guidelines favor tenecteplase over alteplase due to its logistical advantages. Transitioning services to tenecteplase requires consideration of education and training for all relevant staff (medical, nursing, pharmacy) and should address physician concerns. Use of stroke-specific tenecteplase 25 mg dose vials is strongly preferable to minimize the chance of dosing errors that might arise from use of cardiac-dose tenecteplase. Some off-label uses of alteplase are supported by positive randomized controlled trial data (wake-up and unknown onset stroke, and imaging-supported late window use 4.5-9 h after onset) while equivalent data for tenecteplase are less conclusive. Trial data comparing tenecteplase to control give relevant safety data for both wake-up / unknown onset stroke and for late time windows, and some efficacy data favor tenecteplase in a late time window. Given the weight of evidence for biologically similar efficacy and safety of tenecteplase 0.25 mg/kg, and potential for dosing errors, retention of alteplase for off-label indications should not be recommended.

Rationale: Early mortality in intracerebral hemorrhage (ICH) is due to hematoma volume (HV) expansion, and there are no effective treatments available other than reduction in blood pressure. Tranexamic acid (TXA) a hemostatic drug that is widely available and safe can be a cost-effective treatment for ICH, if proven efficacious.

Hypothesis: Administration of TXA in ICH patients when given within 4.5 h of symptom onset will reduce early mortality at 30 days.

Design: Indian Trial of Tranexamic acid in Spontaneous Intracerebral Haemorrhage (INTRINSIC trial) is a multicenter, randomized, open-label, trial enrolling patients aged more than 18 years presenting with non-traumatic ICH within 4.5 h of symptom onset or when last seen well. Study participants received 2 g of TXA administered within 45 min while control group received standard of care. Intensive blood pressure reduction as per INTERACT 2 protocol is followed is done in both groups. Study plans to recruit 3400 patients. Primary outcome is mortality at day 30. Secondary outcomes are radiological reduction in HV at 24 h from baseline, neurological impairment at day 7 or earlier (if discharged), and assessments of dependency and quality of life at day 90.

Summary: If proven to be beneficial, TXA will have a major impact on medical management of ICH.

Trial registration: Clinical Trial Registry India (CTRI/2023/03/050224) and Clinical Trials.gov (NCT05836831).

Background: In the Oxford Haemodynamic Adaptation to Reduce Pulsatility trial (OxHARP), sildenafil increased cerebrovascular reactivity but did not reduce cerebral pulsatility, a marker of vascular aging. This analysis of OxHARP tested whether these potentially causative mechanisms were independently associated with the severity of white matter hyperintensities (WMHs).

Aims: The aims were to determine independence of the relationship between severity of WMHs with both cerebral pulsatility and cerebrovascular reactivity in the same population.

Methods: OxHARP was a double-blind, randomized, placebo-controlled, crossover trial of phosphodiesterase inhibitors in patients with mild-to-moderate WMH and previous minor cerebrovascular events. It determined effects on cerebrovascular pulsatility and reactivity on transcranial ultrasound and reactivity on magnetic resonance imaging (MRI). Associations were determined between baseline ultrasound measures, and averaged MRI measures across follow-up, with the severity of WMH on clinical imaging (Fazekas or modified Blennow scores) and WMH volume in the MRI substudy, by ordinal and linear regression.

Results: In 75/75 patients (median 70 years, 78% male), cerebral pulsatility was associated with age (p < 0.001) whereas reactivity on ultrasound was not (p = 0.29). Severity of WMH in all participants was independently associated with decreased cerebrovascular reactivity and increased cerebral pulsatility (pulsatility p = 0.016; reactivity p = 0.03), with a trend to a synergistic interaction (p = 0.075). Reactivity on ultrasound was still associated with WMH after further adjustment for age (p = 0.017), but pulsatility was not (p = 0.31). Volume of WMH in the MRI substudy was also independently associated with both markers on ultrasound (pulsatility p = 0.005; reactivity p = 0.029) and was associated with reduced cerebrovascular reactivity within WMH on MRI (p < 0.0001).

Conclusion: WMHs are independently associated with cerebral pulsatility and reactivity, representing complementary potential disease mechanisms and treatment targets.

Trial registration: clinicaltrials.org: https://classic.clinicaltrials.gov/ct2/show/NCT03855332.

Background and aims: The clinical evolution of acute ischemic stroke patients with isolated proximal posterior cerebral artery (PCA) occlusion treated with medical management alone has been poorly described. We aimed to determine the clinical and radiological factors associated with poor functional outcome in this population.

Methods: We conducted a multicenter international retrospective study of consecutive stroke patients with isolated occlusion of the first (P1) or second (P2) segment of PCA admitted within 6 h from symptoms onset in 26 stroke centers in France, Switzerland, and the United States, treated with the best medical management alone. Poor functional outcome was defined as a modified Rankin scale (mRS) ⩾2 at 3 months or no return to pre-stroke mRS. The associations between pretreatment variables and poor outcome were studied in univariable and then multivariable analyses, as well as the association between poor outcome and key follow-up radiological variables.

Results: Overall, 585 patients were included. The median age was 74 years (interquartile range (IQR) = 63-83), median National Institutes of Health Stroke Scale (NIHSS) was 6 (3-10), 80% received intravenous thrombolysis (IVT), and 22% and 78% had P1 and P2 occlusions, respectively. Poor outcome occurred in 56% of patients. In multivariable analysis focusing on pretreatment variables, age (adjusted odds ratio (OR) = 1.12 per 5-year increase [95% confidence interval (CI) = 1.05-1.20]; p = 0.001), NIHSS score (aOR = 1.12 per each point increase [1.08-1.18]; p < 0.001), infarct volume (aOR = 1.16 per 5 mL increase [1.07-1.25]; p < 0.001), and the lack of IVT use (aOR = 1.79 [1.10-2.94], p = 0.020) were independently associated with poor outcome. Regarding 24-h follow-up radiological variables, complete recanalization (defined as no clot in the vascular tree at or beyond the primary occlusive lesion, aOR = 0.37 [95% CI = 0.21-0.65], p < 0.001) and parenchymal hematoma occurrence (aOR = 2.37 [95% CI = 1.01-5.56], p = 0.048) were independently associated with poor 3-month outcome.

Conclusions: Poor outcome occurred in more than half of medically treated PCA-related acute stroke patients. Facilitating IVT use may improve functional outcome. Therapeutic approaches aimed at enhancing recanalization and reducing hemorrhagic transformation need to be studied in clinical trials.

Background: Intensive blood pressure (BP) management within 24 h after successful reperfusion following endovascular thrombectomy (EVT) is associated with worse functional outcomes than conventional BP management in Asian randomized controlled trials. Given the high prevalence of intracranial atherosclerotic stenosis (ICAS) in Asia, ICAS may influence these outcomes.

Aims: We aimed to assess whether ICAS affects the outcomes of intensive BP management after successful EVT.

Methods: We conducted a secondary analysis of the Outcome in Patients Treated With Intra-Arterial Thrombectomy-Optimal Blood Pressure Control trial, which enrolled participants from June 2020 to November 2022. Patients with anterior circulation large vessel occlusion (LVO) were stratified into ICAS-related and embolic LVO groups. Clinical outcomes for intensive (target systolic BP < 140 mm Hg) and conventional BP management (target systolic BP = 140-180 mm Hg) were analyzed in each group. The primary outcome was a favorable outcome, defined as a modified Rankin Scale score of 0 to 2 at 3 months. Safety outcomes included symptomatic intracerebral hemorrhage within 36 h and stroke-related death within 3 months.

Results: Among 192 patients, 59 were in the ICAS-related LVO group, and 133 were in the embolic LVO group. In the ICAS-related LVO group, the rate of achieving a favorable outcome at 3 months was 37.5% with intensive BP management and 55.6% with conventional management (adjusted odds ratio (OR) = 0.49 (95% confidence interval (CI) = 0.14 to 1.75); P = 0.27). In the embolic LVO group, these rates were 29.9% and 42.4%, respectively (adjusted OR = 0.64 (95% CI = 0.28 to 1.45); P = 0.29). No significant interaction was found (P for interaction = 0.68). In addition, the ICAS-related LVO group receiving intensive BP management had lower rates of successful reperfusion at 24 h compared to conventional management (67.7% vs. 91.7%; P = 0.03), while no significant difference was found in the embolic LVO group. A significant interaction effect on successful reperfusion at 24 h was observed between ICAS-related and embolic LVO groups (P for interaction = 0.04). No significant differences in safety outcomes were observed between intensive BP management and conventional management within both ICAS-related LVO and embolic LVO groups.

Conclusions: ICAS did not significantly affect outcomes of intensive BP management within 24 h after successful EVT. After successful reperfusion by EVT, intensive BP management should be avoided regardless of ICAS presence.

Data access statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.