Tranexamic acid versus placebo in individuals with intracerebral haemorrhage treated within 2 h of symptom onset (STOP-MSU): an international, double-blind, randomised, phase 2 trial.

BACKGROUND: Tranexamic acid, an antifibrinolytic agent, might attenuate haematoma growth after an intracerebral haemorrhage. We aimed to determine whether treatment with intravenous tranexamic acid within 2 h of an intracerebral haemorrhage would reduce haematoma growth compared with placebo. METHODS: STOP-MSU was an investigator-led, double-blind, randomised, phase 2 trial conducted at 24 hospitals and one mobile stroke unit in Australia, Finland, New Zealand, Taiwan, and Viet Nam. Eligible participants had acute spontaneous intracerebral haemorrhage confirmed on non-contrast CT, were aged 18 years or older, and could be treated with the investigational product within 2 h of stroke onset. Using randomly permuted blocks (block size of 4) and a concealed pre-randomised assignment procedure, participants were randomly assigned (1:1) to receive intravenous tranexamic acid (1 g over 10 min followed by 1 g over 8 h) or placebo (saline; matched dosing regimen) commencing within 2 h of symptom onset. Participants, investigators, and treating teams were masked to group assignment. The primary outcome was haematoma growth, defined as either at least 33% relative growth or at least 6 mL absolute growth on CT at 24 h (target range 18-30 h) from the baseline CT. The analysis was conducted within the estimand framework with primary analyses adhering to the intention-to-treat principle. The primary endpoint and secondary safety endpoints (mortality at days 7 and 90 and major thromboembolic events at day 90) were assessed in all participants randomly assigned to treatment groups who did not withdraw consent to use any data. This study was registered with ClinicalTrials.gov, NCT03385928, and the trial is now complete. FINDINGS: Between March 19, 2018, and Feb 27, 2023, 202 participants were recruited, of whom one withdrew consent for any data use. The remaining 201 participants were randomly assigned to either placebo (n=98) or tranexamic acid (n=103; intention-to-treat population). Median age was 66 years (IQR 55-77), and 82 (41%) were female and 119 (59%) were male; no data on race or ethnicity were collected. CT scans at baseline or follow-up were missing or of inadequate quality in three participants (one in the placebo group and two in the tranexamic acid group), and were considered missing at random. Haematoma growth occurred in 37 (38%) of 97 assessable participants in the placebo group and 43 (43%) of 101 assessable participants in the tranexamic acid group (adjusted odds ratio [aOR] 1·31 [95% CI 0·72 to 2·40], p=0·37). Major thromboembolic events occurred in one (1%) of 98 participants in the placebo group and three (3%) of 103 in the tranexamic acid group (risk difference 0·02 [95% CI -0·02 to 0·06]). By 7 days, eight (8%) participants in the placebo group and eight (8%) in the tranexamic acid group had died (aOR 1·08 [95% CI 0·35 to 3·35]) and by 90 days, 15 (15%) participants in the placebo group and 19 (18%) in the tranexamic acid group had died (aOR 1·61 [95% CI 0·65 to 3·98]). INTERPRETATION: Intravenous tranexamic acid did not reduce haematoma growth when administered within 2 h of intracerebral haemorrhage symptom onset. There were no observed effects on other imaging endpoints, functional outcome, or safety. Based on our results, tranexamic acid should not be used routinely in primary intracerebral haemorrhage, although results of ongoing phase 3 trials will add further context to these findings. FUNDING: Australian Government Medical Research Future Fund.

Cerebral tau pathology in cerebral amyloid angiopathy.

Tau, a hallmark of Alzheimer's disease, is poorly characterized in cerebral amyloid angiopathy. We aimed to assess the clinico-radiological correlations between tau positron emission tomography scans and cerebral amyloid angiopathy. We assessed cerebral amyloid and hyperphosphorylated tau in patients with probable cerebral amyloid angiopathy (n = 31) and hypertensive small vessel disease (n = 27) using 11C-Pittsburgh compound B and 18F-T807 positron emission tomography. Multivariable regression models were employed to assess radio-clinical features related to cerebral tau pathology in cerebral amyloid angiopathy. Cerebral amyloid angiopathy exhibited a higher cerebral tau burden in the inferior temporal lobe [1.25 (1.17-1.42) versus 1.08 (1.05-1.22), P < 0.001] and all Braak stage regions of interest (P < 0.05) than hypertensive small vessel disease, although the differences were attenuated after age adjustment. Cerebral tau pathology was significantly associated with cerebral amyloid angiopathy-related vascular markers, including cortical superficial siderosis (ß = 0.12, 95% confidence interval 0.04-0.21) and cerebral amyloid angiopathy score (ß = 0.12, 95% confidence interval 0.03-0.21) after adjustment for age, ApoE4 status and whole cortex amyloid load. Tau pathology correlated significantly with cognitive score (Spearman's ρ=-0.56, P = 0.001) and hippocampal volume (-0.49, P = 0.007), even after adjustment. In conclusion, tau pathology is more frequent in sporadic cerebral amyloid angiopathy than in hypertensive small vessel disease. Cerebral amyloid angiopathy-related vascular pathologies, especially cortical superficial siderosis, are potential markers of cerebral tau pathology suggestive of concomitant Alzheimer's disease.

Predicting ischemic stroke patients' prognosis changes using machine learning in a nationwide stroke registry.

Accurately predicting the prognosis of ischemic stroke patients after discharge is crucial for physicians to plan for long-term health care. Although previous studies have demonstrated that machine learning (ML) shows reasonably accurate stroke outcome predictions with limited datasets, to identify specific clinical features associated with prognosis changes after stroke that could aid physicians and patients in devising improved recovery care plans have been challenging. This study aimed to overcome these gaps by utilizing a large national stroke registry database to assess various prediction models that estimate how patients' prognosis changes over time with associated clinical factors. To properly evaluate the best predictive approaches currently available and avoid prejudice, this study employed three different prognosis prediction models including a statistical logistic regression model, commonly used clinical-based scores, and a latest high-performance ML-based XGBoost model. The study revealed that the XGBoost model outperformed other two traditional models, achieving an AUROC of 0.929 in predicting the prognosis changes of stroke patients followed for 3 months. In addition, the XGBoost model maintained remarkably high precision even when using only selected 20 most relevant clinical features compared to full clinical datasets used in the study. These selected features closely correlated with significant changes in clinical outcomes for stroke patients and showed to be effective for predicting prognosis changes after discharge, allowing physicians to make optimal decisions regarding their patients' recovery.

Prevalence and clinical features of carotid artery web in patients undergoing endovascular thrombectomy for acute ischemic stroke.

PURPOSE: Carotid artery web (CaW) is a rare focal fibromuscular dysplasia that can lead to embolic strokes with large vessel occlusion. This condition can be effectively treated with endovascular thrombectomy (EVT). Our study aims to assess the prevalence of CaW among patients with acute ischemic stroke (AIS) who underwent EVT and to compare the clinical characteristics of CaW with other carotid artery pathologies. METHODS: We enrolled consecutive patients with AIS who underwent EVT at a single medical center and two regional teaching hospitals in Taiwan from September 2014 to December 2021. We compared CaW with carotid dissection (CaD) and carotid large artery atherosclerosis (CaLAA) in terms of patient demographics and thrombus histological findings. RESULTS: Of the 576 AIS patients who underwent EVT, four (mean age: 50 years) were diagnosed with CaW, resulting in a prevalence of 0.69%. Among these four patients, three experienced successful reperfusion after EVT and achieved functional independence (defined as a modified Rankin Scale score ≤2) three months post-stroke. Importantly, none of the CaW patients suffered a recurrent stroke within one year. Patients with CaW were younger than those with CaD or CaLAA, and exhibited fewer vascular risk factors. Additionally, CaW was associated with distal occlusion sites. The thrombus composition in CaW patients was similar to that in CaD patients. CONCLUSIONS: In conclusion, CaW is a rare finding among Asian patients with carotid artery disease who undergo for AIS. It is more prevalent in younger patients with a limited number of vascular risk factors.

Impact of Early Mobilization on Patients With Acute Ischemic Stroke Treated With Thrombolysis or Thrombectomy: A Randomized Controlled Trial.

BACKGROUND: Early mobilization (EM) within 24 to 72 hours post-stroke may improve patients' performance and ability. However, after intravenous thrombolysis (IVT) or mechanical thrombectomy (MT), the increased risk of hemorrhagic complications impacts the implementation of early out-of-bed mobilization. Few studies have investigated EM after IVT or MT for acute ischemic stroke (AIS), and its impact in these patients is unknown. OBJECTIVE: To investigate the effect of EM on AIS treated with IVT or MT.|. METHODS: We recruited 122 patients with first AIS; 60 patients were treated with IVT, and 62 patients were treated with MT. For each IVT and MT cohort, the control groups received standard early rehabilitation, and the intervention groups received an EM protocol. The training lasted 30 minutes/day, 5 days/week until discharge. MAIN OUTCOMES MEASURES: The effectiveness of the interventions was evaluated using the motor domain of the Functional Independence Measure (FIM-motor) and the Postural Assessment Scale for Stroke Patients (PASS) at baseline, 2-week, 4-week, and 3-month post-stroke, the Functional Ambulation Category 2-week post-stroke, and the total length of stay at the stroke center. RESULTS: Both IVT and MT treatment groups showed improved FIM-motor and PASS scores over time; however, only the IVT EM group had significantly improved FIM-motor performance within 1 month after stroke than the control group. Conclusion. An EM protocol with the same intervention time and session frequency per day as in the standard care protocol was effective in improving the functional ability of stroke patients after IVT.

Comparing Low- or Standard-Dose Alteplase in Endovascular Thrombectomy: Insights From a Nationwide Registry.

BACKGROUND: Timely intravenous thrombolysis and endovascular thrombectomy are the standard reperfusion treatments for large vessel occlusion stroke. Currently, it is unknown whether a low-dose thrombolytic agent (0.6 mg/kg alteplase) can offer similar efficacy to the standard dose (0.9 mg/kg alteplase). METHODS: We enrolled consecutive patients in the multicenter Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke who had received combined thrombolysis (within 4.5 hours of onset) and thrombectomy treatment from January 2019 to April 2023. The choice of low- or standard-dose alteplase was based on the physician's discretion. The outcomes included successful reperfusion (modified Thrombolysis in Cerebral Infarction score, 2b-3), symptomatic intracerebral hemorrhage, 90-day modified Rankin Scale score, and 90-day mortality. The outcomes between the 2 groups were compared using multivariable logistic regression and inverse probability of treatment weighting-adjusted analysis. RESULTS: Among the 2242 patients in the Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke, 734 (33%) received intravenous alteplase. Patients in the low-dose group (n=360) were older, had more women, more atrial fibrillation, and longer onset-to-needle time compared with the standard-dose group (n=374). In comparison to low-dose alteplase, standard-dose alteplase was associated with a lower rate of successful reperfusion (81% versus 87%; adjusted odds ratio, 0.63 [95% CI, 0.40-0.98]), a numerically higher incidence of symptomatic intracerebral hemorrhage (6.7% versus 3.9%; adjusted odds ratio, 1.81 [95% CI, 0.88-3.69]), but better 90-day modified Rankin Scale score (functional independence [modified Rankin Scale score, 0-2], 47% versus 31%; adjusted odds ratio, 1.91 [95% CI, 1.28-2.86]), and a numerically lower mortality rate (9% versus 15%; adjusted odds ratio, 0.73 [95% CI, 0.43-1.25]) after adjusting for covariates. Similar results were observed in the inverse probability of treatment weighting-adjusted models. The results were consistent across predefined subgroups and age strata. CONCLUSIONS: Despite the lower rate of successful reperfusion and higher risk of symptomatic intracerebral hemorrhage with standard-dose alteplase, standard-dose alteplase was associated with a better functional outcome in patients receiving combined thrombolysis and thrombectomy.

Sex Differences in the Role of Multimorbidity on Poststroke Disability: The Taiwan Stroke Registry.

BACKGROUND AND OBJECTIVES: Multimorbidity is common in patients who experience stroke. Less is known about the effect of specific multimorbidity patterns on long-term disability in patients with stroke. Furthermore, given the increased poststroke disability frequently seen in female vs male patients, it is unknown whether multimorbidity has a similar association with disability in both sexes. We assessed whether specific multimorbidity clusters were associated with greater long-term poststroke disability burden overall and by sex. METHODS: In the Taiwan Stroke Registry, an ongoing nationwide prospective registry, patients with first-ever ischemic stroke were enrolled; this analysis is restricted to those individuals surviving to at least 6 months poststroke. Using a hierarchical clustering approach, clusters of prestroke multimorbidity were generated based on 16 risk factors; the algorithm identified 5 distinct clusters. The association between clusters and 12-month poststroke disability, defined using the modified Rankin Scale (mRS), was determined using logistic regression models, with additional models stratified by sex. The longitudinal association between multimorbidity and functional status change was assessed using mixed-effects models. RESULTS: Nine-thousand eight hundred eighteen patients with first-ever ischemic stroke were included. The cluster with no risk factors was the reference, "healthier" risk group (N = 1,373). Patients with a cluster profile of diabetes, peripheral artery disease (PAD), and chronic kidney disease (CKD) (N = 1882) had significantly greater disability (mRS ≥ 3) at 1 month (OR [95% CI] = 1.36 [1.13-1.63]), 3 months (OR [95% CI] = 1.27 [1.04-1.55]), and 6 months (OR [95% CI] = 1.30 [1.06-1.59]) but not at 12 months (OR [95% CI] = 1.16 [0.95-1.42]) than patients with a healthier risk factor profile. In the sex-stratified analysis, the associations with this risk cluster remained consistent in male patients (OR [95% CI] = 1.42 [1.06-1.89]) at 12 months, who also had a higher comorbidity burden, but not in female patients (OR [95% CI] = 0.95 [0.71-1.26]), who had higher proportions of severe strokes and severe disability (p-interaction = 0.04). DISCUSSION: Taiwanese patients with multimorbidity, specifically the concurrent presence of diabetes, PAD, and CKD, had higher odds of a worse functional outcome in the first 6 months poststroke. Clusters of multimorbidity may be less informative for long-term disability in female patients. Further studies should evaluate other mechanisms for worse disability in female patients poststroke.

Differences in lobar microbleed topography in cerebral amyloid angiopathy and hypertensive arteriopathy.

Lobar cerebral microbleeds are a characteristic neuroimaging finding in cerebral amyloid angiopathy (CAA) but can also be found in hypertensive arteriolosclerosis. We aimed to investigate whether CAA is more associated with intracortical lobar microbleeds than hypertensive arteriosclerosis. Ninety-one survivors of spontaneous intracerebral hemorrhage with at least one lobar microbleed were included and underwent brain MRI and amyloid PET. We categorized lobar microbleeds as intracortical, juxtacortical, or subcortical. We assessed the associations between the lobar microbleed categories and microangiopathy subtypes or cerebral amyloid load based on the Pittsburgh Compound-B PET standardized uptake value ratio (SUVR). Patients with CAA had a higher prevalence of intracortical lobar microbleeds (80.0% vs. 50.8%, P = 0.011) and lower prevalence of subcortical lobar microbleeds (13.3% vs. 60.1%, P < 0.001) than patients with hypertensive arteriolosclerosis. Strictly intracortical/juxtacortical lobar microbleeds were associated with CAA (OR 18.9 [1.9-191.4], P = 0.013), while the presence of subcortical lobar microbleeds was associated with hypertensive arteriolosclerosis (OR 10.9 [1.8-68.1], P = 0.010). Amyloid retention was higher in patients with strictly intracortical/juxtacortical CMBs than those without (SUVR = 1.15 [1.05-1.52] vs. 1.08 [1.02-1.19], P = 0.039). Amyloid retention positively correlated with the number of intracortical lobar microbleeds (P < 0.001) and negatively correlated with the number of subcortical lobar microbleeds (P = 0.018). CAA and cortical amyloid deposition are more strongly associated with strictly intracortical/juxtacortical microbleeds than subcortical lobar microbleeds. Categorization of lobar microbleeds based on anatomical location may help differentiate the underlying microangiopathy and potentially improve the accuracy of current neuroimaging criteria for cerebral small vessel disease.

Dynamic changes and lifetime effect of functional disability profiles for stroke patients: real-world evidence from South Korea.

PURPOSE: This work aimed to investigate the long-term dynamic changes of functional disabilities and estimate lifetime outcomes of different functional disabilities after a stroke, using real-world data from a nationally representative South Korean cohort. METHODS: Patients aged 18 and above with ischemic and hemorrhagic strokes were identified from the Korea Health Panel (KHP) data (2008-2018). Functional disabilities were repeatedly measured for patients aged 55 and over for the prevalence of disabilities associated with activities of daily living (ADL), and kernel smoothing means were estimated for each item. The lifetime survival function of stroke patients in Korea was adopted from another study utilizing the National Health Insurance Service of Korea's national sample cohort. By multiplying the disability-free proportion with the survival function throughout life, disability-free life expectancy (DFLE) for each ADL item was estimated. The loss-of-DFLE was calculated by subtracting the DFLE from age-, sex-, and calendar year-matched referents simulated from Korean life tables. RESULTS: The KHP dataset included 466 stroke patients. The overall functional disability needs increased over time after stroke diagnosis. DFLE was lowest for bathing (10.1 years for ischemic stroke and 12.8 years for hemorrhagic stroke), followed by those for dressing and washing. Loss-of-DFLE was highest for bathing for ischemic and hemorrhagic strokes (7.2 and 10.7 years, respectively), indicating that this task required the most assistance for stroke patients compared with the other tasks. DFLEs were slightly lower than the quality-adjusted life expectancy of stroke patients. CONCLUSION: Our findings provide valuable insights for resource allocation and policy decisions in long-term stroke care, potentially enhancing the quality of life for stroke survivors and caregivers.

Impact of cerebral small vessel disease burden and drug level at admission on direct oral anticoagulant associated intracerebral hemorrhage.

INTRODUCTION: Direct oral anticoagulant (DOAC)-associated intracerebral hemorrhage (ICH) is a catastrophic complication. The aim of this study was to investigate the association between computed tomography (CT)-based cerebrovascular small vessel disease (SVD) burden and DOAC-ICH as well as the DOAC concentration upon hospital admission and ICH outcome. PATIENTS AND METHODS: The study included two cohorts: (1) DOAC-ICH: patients who suffered from DOAC-ICH and underwent drug level measurements upon admission; (2) DOAC-non-ICH: stable DOAC users who underwent head CT without ICH during treatment. We categorized the DOAC levels of the DOAC-ICH patients as low (<50 ng/mL), medium (50-300 ng/mL), and high (>300 ng/mL). The CT-based SVD burden (including white matter lesions [WML], lacunes, and cerebral atrophy) was evaluated, and SVD scores (range, 0-3) were used to evaluate SVD severity. RESULTS: A total of 43 DOAC-ICH patients and 177 DOAC-non-ICH patients were enrolled. DOAC-ICH patients were more likely to have WML, lacunes, or cerebral atrophy compared to DOAC-non-ICH patients. After adjustment, the SVD burden was associated with DOAC-ICH, with a higher risk of more severe SVD (SVD score of 2; odds ratio [OR], 10.3 [3.17, 33.3]; score of 3; OR, 16.8 [4.50, 62.6]). The proportions of patients with high, medium, and low drug levels in the DOAC-ICH group were 16.3%, 55.8%, and 27.9%, respectively. Additionally, the high-level group displayed a larger hematoma size and had worse functional outcomes at 3 months than the other two groups. DISCUSSION AND CONCLUSION: The severity of SVD burden was associated with DOAC-ICH. Furthermore, high DOAC levels in ICH were associated with unfavorable clinical outcomes. To address the potential selection bias from these two cohorts, a prospective study to investigate the co-contribution of drug levels and SVD to DOAC-ICH is essential.

Associations of Cerebral Small Vessel Disease on the Features of Hematoma and Hematoma Expansion in Intracerebral Hemorrhage.

INTRODUCTION: Several early noncontrast CT (NCCT) signs of spontaneous intracerebral hemorrhage (ICH) can predict hematoma expansion (HE). However, the associations of underlying cerebral small vessel disease (SVD) on early NCCT signs and HE have been less explored. METHODS: We conducted an analysis of all patients with spontaneous supratentorial ICH and received follow-up imaging between 2016 and 2020 at a stroke center. The early NCCT signs were categorized as shape or density signs. HE was defined as an increase in hematoma volume ≥6 mL or 33% from baseline. The severity of SVD was assessed by both a 3-point CT-based and a 4-point magnetic resonance imaging (MRI)-based SVD score. Regression models were used to examine the associations between SVD score and hematoma volume, NCCT signs, and HE. RESULTS: A total of 328 patients (median age: 64 years; 38% female) were included. The median baseline ICH volume was 8.6 mL, with 38% of the patients had shape signs and 52% had density signs on the initial NCCT. Higher MRI-SVD scores were associated with smaller ICH volumes (p = 0.0006), fewer shape (p = 0.001), or density signs (p = 0.0003). Overall, 16% of patients experienced HE. A higher MRI-SVD score was inversely associated with HE (adjusted odds ratio 0.71, 95% CI: 0.53-0.96). Subgroup analysis revealed that this association was primarily observed in patients who were younger (<65 years), male, had deep hemorrhage, or did not meet the criteria for cerebral amyloid angiopathy diagnosis. CONCLUSIONS: In patients with spontaneous ICH, a more severe SVD was associated with smaller hematoma volume, fewer NCCT signs, and a lower risk of HE. Further research is required to investigate why a higher burden of severely diseased cerebral small blood vessels is associated with less bleeding.

Modifiable vascular risk factors contribute to stroke in 1080 NOTCH3 R544C carriers in Taiwan Biobank.

BACKGROUND AND AIM: Previous studies have suggested cardiovascular risk factors increase the risk of not only common sporadic stroke but also of stroke in patients with monogenic stroke disorders including CADASIL. We investigated the effects of the NOTCH3 Arg544Cys (R544C) variant and associated vascular risk factors on stroke in the Taiwanese population. METHODS: This study was conducted using data from the Taiwan Biobank, consisting of at least 130,000 Han Chinese participants. The genotype was derived from customized genome-wide arrays for 650,000 to 750,000 single-nucleotide polymorphisms (SNPs). Individuals with NOTCH3 R544C were subsequently matched with noncarriers based on the propensity score at a 1:10 ratio by demographic and cardiovascular risk factors. The odds ratio (OR) for stroke or other phenotypes in NOTCH3 R544C carriers and matched noncarriers was then calculated. Univariate and multivariate regression analyses were performed on cardiovascular risk factors in NOTCH3 R544C carriers with and without stroke. The polygenic risk score (PRS) model, adopted from the UK Biobank, was then applied to evaluate the role of NOTCH3 R544C in stroke. RESULTS: From the 114,282 participants with both genotype and questionnaire results, 1080 (0.95%) harbored the pathogenic NOTCH3 R544C variant. When compared to the matched controls (n = 10,800), the carriers presented with a history of stroke (OR: 2.52, 95% confidence interval (CI) (1.45, 4.37)), dementia (OR: 30.1, 95% CI (3.13, 289.43)), and sibling history of stroke (OR: 2.48, 95% CI (1.85, 3.34)) phenotypes. The risk of stroke increased with every 10-year increase in age (p = 0.006, Cochran-Mantel-Haenszel test). Among NOTCH3 R544C carriers, 16 (1.3%) of the 1080 carriers with a stroke history were older, male, and more likely to have hypertension, diabetes, dyslipidemia, and a family history of stroke. In the stepwise multivariate analysis, hypertension (OR: 11.28, 95% CI (3.54, 43.3)) and diabetes mellitus (OR: 4.10, 95% CI (1.31, 12.4)) were independently associated with stroke. Harboring the NOTCH3 R544C variant in the Taiwan Biobank is comparable with a 6.74 standard deviations increase in individual's polygenic risk score for stroke. CONCLUSION: While the NOTCH3 R544C variant alone increased the risk of stroke, modifiable vascular risk factors also played a role in the occurrence of stroke in Taiwanese community-dwelling individuals carrying the NOTCH3 variant.

Mild cognitive impairment estimation based on functional near-infrared spectroscopy.

Patients with mild cognitive impairment (MCI) are at a high risk of developing future dementia. However, early identification and active intervention could potentially reduce its morbidity and the incidence of dementia. Functional near-infrared spectroscopy (fNIRS) has been proposed as a noninvasive modality for detecting oxygenation changes in the time-varying hemodynamics of the prefrontal cortex. This study sought to provide an effective method for detecting patients with MCI using fNIRS and the Wisconsin card sorting test (WCST) to evaluate changes in blood oxygenation. The results revealed that all groups with a lower mini-mental state examination grade had a higher increase in HHb concentration during a modified WCST (MCST). The increase in the change in oxygenated hemoglobin concentration in the stroke group was smaller than that in the normal group due to weak cerebrovascular reactivity.

Patient and hospital characteristics associated with do-not-resuscitate/do-not-intubate orders: a cross-sectional study based on the Taiwan stroke registry.

BACKGROUND: Previous studies of do-not-resuscitate (DNR) or do-not-intubate (DNI) orders in stroke patients have primarily been conducted in North America or Europe. However, characteristics associated with DNR/DNI orders in stroke patients in Asia have not been reported. METHODS: Based on the Taiwan Stroke Registry, this nationwide cross-sectional study enrolled hospitalized stroke patients from 64 hospitals between 2006 and 2020. We identified characteristics associated with DNR/DNI orders using a two-level random effects model. RESULTS: Among the 114,825 patients, 5531 (4.82%) had DNR/DNI orders. Patients with acute ischemic stroke (AIS) had the highest likelihood of having DNR/DNI orders (adjusted odds ratio [aOR] 1.76, 95% confidence interval [CI] 1.61-1.93), followed by patients with intracerebral hemorrhage (ICH), and patients with subarachnoid hemorrhage (SAH) had the lowest likelihood (aOR 0.53, 95% CI 0.43-0.66). From 2006 to 2020, DNR/DNI orders increased in all three types of stroke. In patients with AIS, women were significantly more likely to have DNR/DNI orders (aOR 1.23, 95% CI 1.15-1.32), while patients who received intravenous alteplase had a lower likelihood (aOR 0.74, 95% CI 0.65-0.84). Patients with AIS who were cared for by religious hospitals (aOR 0.55, 95% CI 0.35-0.87) and patients with SAH who were cared for by medical centers (aOR 0.40, 95% CI 0.17-0.96) were significantly less likely to have DNR/DNI orders. CONCLUSIONS: In Taiwan, DNR/DNI orders increased in stroke patients between 2006 and 2020. Hospital characteristics were found to play a significant role in the use of DNR/DNI orders.

Cerebral amyloid deposition predicts long-term cognitive decline in hemorrhagic small vessel disease.

BACKGROUND: To investigate the association between cerebral amyloid deposition and long-term cognitive outcomes in patients with hemorrhagic small vessel disease (SVD) and survivors of intracerebral hemorrhage (ICH). METHODS: Patients experiencing an ICH without overt dementia were prospectively recruited (n = 68) for brain MRI and Pittsburgh compound B (PiB) positron emission tomography scans at baseline. Cognitive function was assessed using the mini-mental status examination (MMSE) and clinical dementia rating after an overall median follow-up of 3.8 years. A positive amyloid scan was defined as a global PiB standardized uptake value ratio >1.2. Associations between follow-up cognitive outcomes and neuroimaging markers were explored using multivariable Cox regression models. RESULTS: PiB(+) patients were older (72.1 ± 7.8 vs. 59.9 ± 11.7, p = .002) and more frequently had cerebral amyloid angiopathy (CAA) (63.6% vs. 15.8%, p = .002) than PiB(-) patients. PiB(+) was associated with a higher risk of dementia conversion (32.9 vs. 4.0 per 100-person-years, hazard ratio [HR] = 15.7 [3.0-80.7], p = .001) and MMSE score decline (58.8 vs. 9.9 per 100-person-years, HR = 6.2 [1.9-20.0], p = .002). In the non-CAA subgroup (n = 52), PiB(+) remained an independent predictor of dementia conversion, p = .04). In the Cox models, PiB(+) was an independent predictor of dementia conversion (HR = 15.8 [2.6-95.4], p = .003) and MMSE score decline (HR = 5.7 [1.6-20.3], p = .008) after adjusting for confounders. CONCLUSIONS: Cerebral amyloid deposition potentially contributes to long-term cognitive decline in SVD-related ICH.

Interaction between cerebral small vessel disease, blood pressure, and remote ischemic lesions in acute spontaneous intracerebral hemorrhage.

BACKGROUND: Acute blood pressure (BP) reduction is the first-line treatment for acute spontaneous intracerebral hemorrhage (ICH); however, recent research suggests that intensive BP reduction along with cerebral small vessel disease (cSVD) is a risk factor for remote DWI lesions (RDWILs). We aimed to delineate the interplay between cSVD and BP reduction therapy on the risk of RDWILs. METHODS: We enrolled 303 patients who underwent brain magnetic resonance imaging within 7 days after acute spontaneous ICH. RDWILs were categorized as occurring in borderzone (BZ) or non-BZ areas. We examined the effect of cSVD, acute BP reduction, and their interaction on RDWILs. RESULTS: RDWILs were observed in 34 (11%) patients (59.8 ± 10.3-years-old, 24% male). RDWILs were associated with a larger acute weighted average mean arterial pressure (MAP) reduction in the initial 24 h after ICH onset and a higher total cerebral microbleed (CMB) count. Intensive MAP changes (odds ratio (OR) per 10 mmHg 1.76, 95% confidence interval (CI) 1.03-3.20), total CMBs burden (OR per 10 CMBs 1.21, 95% CI 1.08-1.39), and presence of lobar CMBs (OR 7.33, 95% CI 1.59-55.6) were risk factors for RDWILs at BZ, but not at non-BZ. Furthermore, a significant interaction was observed between lobar CMBs and MAP reduction on increased risk of RDWILs at BZ (p = 0.030). CONCLUSION: cSVD modulates the effect of acute BP reduction on the risk of RDWILs. Patients with extensive microangiopathy have a higher risk of developing cerebral ischemic changes in BZ during unstable hemodynamic status.

Association of Ferroptosis with Severity and Outcomes in Acute Ischemic Stroke Patients Undergoing Endovascular Thrombectomy: A Case-control Study.

Ferroptosis, an iron-dependent form of cell death, is characterized by intracellular accumulation of iron and reactive oxygen species-induced lipid peroxidation. Animal experiments have shown the important roles of ferroptosis in ischemic stroke, but the evidence in human stroke is insufficient. This prospective study evaluated the associations between plasma ferroptosis biomarkers at hyperacute stage and long-term outcomes in patients with acute ischemic stroke undergoing endovascular thrombectomy (EVT). The plasma samples were collected immediately before and after EVT (T1 and T2) and at 24 h (T3) for the 126 stroke patients and once for the 50 stroke-free control subjects. Compared with controls, stroke patients had higher 4-hydroxynonenal (4-HNE) levels at T1 and T2 while lower homocysteine and soluble transferrin receptor (sTfR) levels at T3. In stroke patients, higher National Institutes of Health Stroke Scale scores at admission were correlated with higher 4-HNE and lower sTfR levels. Lower Alberta Stroke Program Early CT (ASPECT) scores and larger infarct core volumes on CT perfusion before EVT were correlated with higher 4-HNE and homocysteine levels. After adjusting for significant parameters, homocysteine levels at T2 were significantly associated with poor functional outcome and mortality at 3 months. In the receiver operating characteristic (ROC) models, adding homocysteine levels at T2 and hemoglobin levels to the reference model for predicting poor functional outcome significantly increased the area under the ROC curve. In summary, this study provides evidence that ferroptosis is associated with stroke severity and outcomes in patients with acute ischemic stroke undergoing EVT.

The 2023 Taiwan Stroke Society Guidelines for the management of patients with intracranial atherosclerotic disease.

Intracranial atherosclerotic disease (ICAD) is a major cause of ischemic stroke, especially in Asian populations, which has a high risk of recurrent stroke and cardiovascular comorbidities. The present guidelines aim to provide updated evidence-based recommendations for diagnosis and management of patients with ICAD. Taiwan Stroke Society guideline consensus group developed recommendations for management of patients with ICAD via consensus meetings based on updated evidences. Each proposed class of recommendation and level of evidence was approved by all members of the group. The guidelines cover six topics, including (1) epidemiology and diagnostic evaluation of ICAD, (2) nonpharmacological management of ICAD, (3) medical therapy for symptomatic ICAD, (4) endovascular thrombectomy and rescue therapy for acute ischemic stroke with underlying ICAD, (5) endovascular interventional therapy for postacute symptomatic intracranial arterial stenosis, and (6) surgical treatment of chronic symptomatic intracranial arterial stenosis. Intensive medical treatment including antiplatelet therapy, risk factor control, and life style modification are essential for patients with ICAD.

Association between modifiable vascular risk factors and rapid progression of postradiation carotid artery stenosis.

BACKGROUND: Postradiotherapy carotid vasculopathy is a clinically relevant complication in patients with head and neck cancer receiving radiotherapy. In this study, we investigated the factors associated with the development and progression of carotid artery stenosis (CAS) in such patients. METHODS: Patients who received radiotherapy for head and neck cancers between October 2011 and May 2019 at a medical center in Taiwan were eligible for inclusion in this study. This study included patients who underwent two consecutive carotid duplex examinations within an interval of 1 to 3 years. The factors associated with ≥50% CAS at baseline and follow-up were analyzed. RESULTS: In total, 694 patients (mean age, 57.8 ± 9.9 years; men, 75.2%; nasopharyngeal cancer, 73.3%) were included. The mean interval between radiotherapy and carotid duplex examination was 9.9 ± 5.9 years. At baseline, 103 patients had ≥50% CAS, which was significantly associated with tobacco smoking, hypercholesterolemia, and a prolonged interval between radiotherapy and carotid duplex examination. A total of 586 patients did not have CAS at baseline; of them, 68 developed ≥50% CAS during follow-up. Hypertension and hypercholesterolemia were identified as independent risk factors for CAS progression. CONCLUSION: Modifiable vascular risk factors, such as hypertension and hypercholesterolemia, appear to be significantly associated with the rapid progression of postradiotherapy CAS in patients with head and neck cancer.

Amyloid and tau PET in cerebral amyloid angiopathy-related inflammation two case reports and literature review.

Background: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a clinical syndrome characterized by MRI findings of amyloid-related imaging abnormalities-edema (ARIA-E) suggestive of autoimmune and inflammatory reaction and hemorrhagic evidence of cerebral amyloid angiopathy. The longitudinal variation of amyloid PET and its imaging association with CAA-ri are undetermined. Moreover, tau PET in CAA-ri has been rarely investigated. Method: We retrospectively described two cases of CAA-ri. We provided the temporal change of amyloid and tau PET in the first case, and the cross-sectional finding of amyloid and tau PET in the second case. We also performed a literature review of the imaging features of amyloid PET in reported cases of CAA-ri. Results: In the first case, an 88-year-old male presented with progressive consciousness and gait disturbances over 2 months. MRI showed disseminated cortical superficial siderosis. Amyloid PET prior to and after the CAA-ri revealed focally decreased amyloid load in the region of ARIA-E. In the second case, a 72-year-old male was initially suspected to have central nervous system cryptococcosis but later diagnosed with CAA-ri because of the characteristic MRI features and good response to corticosteroid treatment; a subsequent amyloid scan revealed positive amyloid deposition of the brain. Neither case suggested an association between the region of ARIA-E and higher amyloid uptake on PET before or after onset of CAA-ri. Our literature review revealed variable findings related to amyloid burden in post-inflammatory regions in previously reported CAA-ri cases with available amyloid PET. Our case is the first report of longitudinal changes on amyloid PET and show focal decreases in amyloid load after the inflammatory process. Conclusion: This case series highlights the need to better explore the potential of longitudinal amyloid PET in the understanding of the mechanisms of CAA-ri.