Differential risk factor profile and neuroimaging markers of small vessel disease between lacunar ischemic stroke and deep intracerebral hemorrhage.

Background: Lacunar ischemic stroke (LIS) and deep intracerebral hemorrhage (dICH) are two stroke phenotypes of deep perforator arteriopathy. It is unclear what factors predispose individuals with deep perforator arteriopathy to either ischemic or hemorrhagic events. Objectives: We aimed to investigate risk factors and neuroimaging features of small vessel disease (SVD) associated with LIS versus dICH in a cross-sectional study. Methods: We included patients with clinically presenting, magnetic resonance imaging-confirmed LIS or dICH from two tertiary hospitals between 2010 and 2021. We recorded vascular risk factors and SVD markers, including lacunes, white matter hyperintensities (WMH), perivascular spaces (PVS), and cerebral microbleeds (CMB). Logistic regression modeling was used to determine the association between vascular risk factors, SVD markers, and stroke phenotype. We further created WMH probability maps to compare WMH distribution between LIS and dICH. Results: A total of 834 patients with LIS (mean age 61.7 ± 12.1 years) and 405 with dICH (57.7 ± 13.2 years) were included. Hypertension was equally frequent between LIS and dICH (72.3% versus 74.8%, p = 0.349). Diabetes mellitus, hyperlipidemia, smoking, and prior ischemic stroke were more associated with LIS [odds ratio (OR) (95% confidence interval (CI)), 0.35 (0.25-0.48), 0.32 (0.22-0.44), 0.31 (0.22-0.44), and 0.38 (0.18-0.75)]. Alcohol intake and prior ICH were more associated with dICH [OR (95% CI), 2.34 (1.68-3.28), 2.53 (1.31-4.92)]. Lacunes were more prevalent in LIS [OR (95% CI) 0.23 (0.11-0.43)], while moderate-to-severe basal-ganglia PVS and CMB were more prevalent in dICH [OR (95% CI) 2.63 (1.35-5.27), 4.95 (2.71-9.42)]. WMH burden and spatial distribution did not differ between groups. Conclusion: The microangiopathy underlying LIS and dICH reflects distinct risk profiles and SVD features, hence possibly SVD subtype susceptibility. Prospective studies with careful phenotyping and genetics are needed to clarify the mechanisms underlying this difference.

Association of Serum Macrophage Migration Inhibitory Factor with 3-Month Poor Outcome and Malignant Cerebral Edema in Patients with Large Hemispheric Infarction.

BACKGROUND: We aimed to investigate the associations of macrophage migration inhibitory factor (MIF), toll-like receptors 2 and 4 (TLR2/4), and matrix metalloproteinase 9 (MMP9) with 3-month poor outcome, death, and malignant cerebral edema (MCE) in patients with large hemispheric infarction (LHI). METHODS: Patients with LHI within 24 h of onset were enrolled consecutively. Serum MIF, TLR2/4, and MMP9 concentrations on admission were measured. Poor outcome was defined as a modified Rankin Scale score of ≥ 3 at 3 months. MCE was defined as a decreased level of consciousness, anisocoria and midline shift > 5 mm or basal cistern effacement, or indications for decompressive craniectomy during hospitalization. The cutoff values for MIF/MMP9 were obtained from the receiver operating characteristic curve. RESULTS: Of the 130 patients with LHI enrolled, 90 patients (69.2%) had 3-month poor outcome, and MCE occurred in 55 patients (42.3%). Patients with serum MIF concentrations ≤ 7.82 ng/mL for predicting 3-month poor outcome [adjusted odds ratio (OR) 2.827, 95% confidence interval (CI) 1.144-6.990, p = 0.024] also distinguished death (adjusted OR 4.329, 95% CI 1.841-10.178, p = 0.001). Similarly, MMP9 concentrations ≤ 46.56 ng/mL for predicting 3-month poor outcome (adjusted OR 2.814, 95% CI 1.236-6.406, p = 0.014) also distinguished 3-month death (adjusted OR 3.845, 95% CI 1.534-9.637, p = 0.004). CONCLUSIONS: Lower serum MIF and MMP9 concentrations at an early stage were independently associated with 3-month poor outcomes and death in patients with LHI. These findings need further confirmation in larger sample studies.

The association between hypertensive angiopathy and cerebral amyloid angiopathy in primary intracerebral hemorrhage.

Objective: To determine the association between the burden of cerebral small vessel disease (CSVD) due to hypertensive angiopathy (HA) and cerebral amyloid angiopathy (CAA) on MRI in patients with primary intracerebral hemorrhage (ICH). Methods: Patients with primary ICH admitted to our center from March 2012 to November 2021 were consecutively enrolled. We used multivariate binary and ordinal regression analyses to assess the association between HA-CSVD burden and CAA-CSVD burden. Lobar cerebral microbleeds (CMBs) were categorized into three level of severity: 0-1, 2-4, and ≥ 5 lobar CMBs. A high CAA-CSVD score was defined as a CAA-CSVD score of ≥3. Results: Overall, 222 participants (mean age 59.88 ± 13.56) were included into analysis. Age and ICH etiology differed among different lobar CMB severity and between the presence and absence of high CAA-CSVD score (all p < 0.05). Positive associations between HA-related markers and both lobar CMB severity and high CAA-CSVD score (p < 0.05 for the presence of lacune, deep CMBs ≥5, the presence of WMH, and HA-CSVD score) were observed in univariate analysis. These associations remained significant after adjusting for age, sex, ICH etiology, and potential vascular risk factors. The distribution of CAA-CSVD score was significantly different between patients with and without CMBs ≥5 (adjusted OR 2.351, 95% CI 1.242-4.455, p = 0.009) after correcting for age, sex, ICH etiology, and vascular risk factors. Conclusion: Our study provides evidence of an association between HA-CSVD and CAA-CSVD in patients with primary ICH, which needs to be verified in future studies.

The attitudes of postgraduate medical students towards the curriculum by degree type: a large-scale questionnaire survey.

BACKGROUND: Chinese medical schools have offered both professional and academic degrees for postgraduate students. However, there is limited information about the attitudes of professional-degree and academic-degree students. We aimed to examine the attitudes of full-time postgraduate students towards the curriculum, stratified by degree type. METHODS: A 29-item online questionnaire was distributed to postgraduate students in West China School of Medicine of Sichuan University in 2020. The questionnaire was designed to collect students' demographic characteristics, attitudes towards curricular provision and content, and classroom organization. A comparison was made between groups based on degree type (academic degree versus professional degree). RESULTS: Overall, 645 out of 908 students at West China School of Medicine completed the questionnaire. Comparing with students pursuing academic degrees, professional-degree students were more interested if the curriculum included specialized knowledge and clinical skills, and expressed concerns over the excessive compulsory courses and inadequate optional courses (p < 0.001), particularly prominent among first-year postgraduate students. Besides, a greater proportion of professional-degree students thought the curriculum was conflict with clinical work to some extent, and they also rated taking attendance in class as less reasonable (p < 0.01). Conversely, students pursuing academic degrees expressed that the courses were inadequate in interdisciplinary curriculum and had some crossover or repetition, and they assigned a higher importance rating for the curriculum when comparing professional-degree students (all p < 0.05). CONCLUSIONS: Different attitudes toward the curriculum are observed between students pursuing professional degrees and those pursuing academic degrees. This study provides benchmark data for future postgraduate course reforms in China.

Pathological Changes of Small Vessel Disease in Intracerebral Hemorrhage: a Systematic Review and Meta-analysis.

In intracerebral hemorrhage (ICH) with pathology-proven etiology, we performed a systematic review and meta-analysis to elucidate the association between cerebral amyloid angiopathy (CAA) and arteriolosclerosis, and directly compared MRI and pathological changes of markers of cerebral small vessel disease (CSVD). Studies enrolling primary ICH who had received an etiological diagnosis through biopsy or autopsy were searched using Ovid MEDLINE, PubMed, and Web of Science from inception to June 8, 2022. We extracted pathological changes of CSVD for each patient whenever available. Patients were grouped into CAA + arteriolosclerosis, strict CAA, and strict arteriolosclerosis subgroups. Of 4155 studies identified, 28 studies with 456 ICH patients were included. The frequency of lobar ICH (p<0.001) and total microbleed number (p=0.015) differed among patients with CAA + arteriolosclerosis, strict CAA, and strict arteriolosclerosis. Concerning pathology, severe CAA was associated with arteriolosclerosis (OR 6.067, 95% CI 1.107-33.238, p=0.038), although this association was not statistically significant after adjusting for age and sex. Additionally, the total microbleed number (median 15 vs. 0, p=0.006) was higher in ICH patients with CAA evidence than those without CAA. The pathology of CSVD imaging markers was mostly investigated in CAA-ICH. There was inconsistency concerning CAA severity surrounding microbleeds. Small diffusion-weighted imaging lesions could be matched to acute microinfarct histopathologically. Studies that directly correlated MRI and pathology of lacunes, enlarged perivascular spaces, and atrophy were scarce. Arteriolosclerosis might be associated with severe CAA. The pathological changes of CSVD markers by ICH etiology are needed to be investigated further.

Echocardiographic correlates of MRI imaging markers of cerebral small-vessel disease in patients with atrial-fibrillation-related ischemic stroke.

Background and objectives: Atrial fibrillation (AF) has been linked to dementia risk, partly explained by cerebral small vessel disease (CSVD). Since AF and cardiovascular comorbidities were associated with cardiac dysfunction, we aimed to determine the association between echocardiographic parameters and neuroimaging markers of CSVD in patients with AF-related ischemic stroke. Methods: This cross-sectional study enrolled patients with AF-related ischemic stroke from March 2013 to December 2019 who underwent transthoracic echocardiography and brain 3T MRI, including T1, T2, Flair, and SWI imaging sequences. We assessed the presence of lacunes and cerebellar microbleeds (CMBs), the severity of white matter hyperintensity (WMH) scored by the Fazekas scale (0-6), and the severity of enlarged perivascular spaces (EPVS) in basal ganglia (BG) and centrum semiovale (CSO) classified into three categories (0-10, 10-25, and >25). CSVD burden was rated on a 0-to-4 ordinal scale. Generalized linear regression analysis and post hoc comparisons with Bonferroni correction were performed to assess the association between various echocardiographic parameters and these lesions, adjusted for demographics and potential confounders. Results: 119 patients (68.38 ± 12.692 years; male 45.4 %) were included for analysis, of whom 55 (46.2%) had lacunes, 40 (33.6%) had CMBs, and median severity for WMH, BG-EPVS, CSO-EPVS, and CSVD burden were 2 (IQR: 1-3), 1 (IQR: 1-2), 1 (IQR: 0-1), and 1 (IQR: 1-2) respectively. In multivariable, fully adjusted models, left ventricular posterior wall thickness (LVPW) was associated with a higher risk of lacunes (RR 1.899, 95% CI: 1.342-2.686) and CSVD burden (RR = 2.081, 95%CI: 1.562-2.070). Right atrial diameter (RAD) was associated with greater CSO-EPVS (RR = 2.243, 95%CI: 1.234-4.075). No echocardiographic parameters were revealed to be associated with CMBs and WMH. Conclusion: In patients with AF-related ischemic stroke, LVPW is associated with a higher risk of lacunes and CSVD burden, while RAD was associated with greater CSO-EPVS. Larger studies are required to determine these associations and to elucidate if these associations can help facilitate cognitive evaluation and brain MRI screening.

Leukoaraiosis Distribution and Cerebral Collaterals: A Systematic Review and Meta-Analysis.

Background and Objective: Microvascular failure might result in the collapse of cerebral collaterals. However, controversy remains regarding the role of leukoaraiosis (LA) in collateral recruitment. We, therefore, performed a systematic review and meta-analysis of the association between LA and cerebral collaterals. Methods: Ovid Medline, PubMed, Embase, Web of Science, and three Chinese databases were searched from inception to August 2021. Two types of cerebral collaterals, including Circle of Willis (CoW) and leptomeningeal collaterals (LC), were investigated separately. Random effect models were used to calculate the pooled odds ratio (OR). Meta-regression and subgroup analyses were performed to explore the potential sources of heterogeneity. Results: From 14 studies (n = 2,451) that fulfilled our inclusion criteria, data from 13 could be pooled for analysis. Overall, there was a significant association between severe LA and incomplete CoW (pooled OR 1.66, 95% CI 1.18-2.32, p = 0.003), with low heterogeneity (I 2 = 5.9%). This association remained significant in deep LA (pooled OR 1.48, 95% CI 1.04-2.11, p = 0.029, I 2 = 0), but not periventricular LA. Similarly, there was a significant association between LA and LC (pooled OR 1.73, 95% CI 1.03-2.90, p = 0.037), but with high heterogeneity (I 2 = 67.2%). Meta-regression indicated a negative association of sample size with the effect sizes (p = 0.029). In addition, most of the studies (7/9) included into the analysis of the relationship of severe LA with poor LC enrolled subjects with large vessel occlusion stroke, and this relationship remained significant when pooling the seven studies, but with high heterogeneity. Conclusion: Severe LA is associated with a higher prevalence of poor collaterals. This association is robust for CoW but weak for LC. Further studies are required to explore the underlying mechanisms.

Circle of Willis Morphology in Primary Intracerebral Hemorrhage.

We aimed to study the distribution of Circle of Willis (CoW) morphology and its association with intracerebral hemorrhage (ICH) etiology and cerebral small vessel disease (CSVD) burden. Patients with primary ICH who had brain MRIs were consecutively enrolled between March 2012 and January 2021. CoW morphology, CSVD features and the combined CSVD burden (including global CSVD burden, total hypertensive arteriopathy [HA] burden, and total cerebral amyloid angiopathy [CAA] burden) were assessed. CoW morphology included poor CoW (defined as CoW score 0-2), incomplete CoW, and complete fetal-variant of the posterior communicating artery (CFPcoA). Among 296 patients enrolled, 215 were included in the analysis. There was no significant difference among HA-, CAA-, and mixed-ICH in each CoW morphology. Exploratory subgroup analyses suggested that poor CoW was associated with a greater incidence of HA-ICH and low incidence of mixed ICH in patients aged < 60 years, while mixed ICH occurred more frequently in patients with CFPcoA, especially in those without hypertension history (all p < 0.050). Additionally, incomplete CoW was correlated with a larger incidence of lacunes (adjusted OR [adOR] 2.114, 95% CI 1.062-4.207), microbleeds ≥ 5 (adOR 2.437, 95% CI 1.187-5.002), and therefore the combined CSVD burden (adOR 1.194, 95% CI 1.004-1.419 for global CSVD burden, adOR 1.343, 95% CI 1.056-1.707 for total CAA burden), independent of modifiable vascular risk factors, but not age and sex. The CoW might therefore have a potential impact on ICH etiology and is associated with a greater CSVD burden. Our findings are novel, and need to be verified in future studies.

Development of cognition decline in non-acute symptomatic patients with cerebral small vessel disease: Non-Acute Symptomatic Cerebral Ischemia Registration study (NASCIR)-rationale and protocol for a prospective multicentre observational study.

INTRODUCTION: Headaches, dizziness and memory loss of unspecific causes are the most common non-acute ischemia symptoms in the ageing population, which are often associated with cerebral small vessel disease (CSVD) imaging markers; however, there is insufficient evidence concerning their association with the development of cognitive decline. This study aims to investigate risk factors, clinical course, cerebral and retinal imaging changes, proteomics features of non-symptomatic ischaemia symptomatic patients with cognitive decline. METHODS AND ANALYSIS: The Non-Acute Symptomatic Cerebral Ischemia Registration study is a multicentre, registry-based, prospective observational study, is designed to investigate the cognitive decline in non-acute ischaemia symptomatic patients. We will recruit 500 non-acute ischaemia symptomatic patients from four tertiary hospitals in China. For this study, non-acute ischaemia symptoms will be defined as headaches, dizziness and memory loss. Patients with headaches, dizziness or memory loss over 50 years of age will be included. Clinical features, cognitive assessment, cerebral and retinal imaging data, and a blood sample will be collected after recruitment. Patients will be followed up by structured telephone interviews at 1, 2, 3, 4, 5 years after recruitment. This study will improve our knowledge of the development of cognitive decline in non-acute ischaemia symptomatic patients and factors affecting the cognitive outcomes, which will eventually elucidate underlying pathways and mechanisms of cognitive decline in these patients and facilitate the optimisation of individualised interventions for its prevention and treatment. ETHICS AND DISSEMINATION: Ethics approval is obtained from The Biomedical Research Ethics Committee of West China Hospital, Sichuan University (Reference No. 2016 (335)). We will present our findings at national and international conferences and peer-reviewed journals in stroke and neurology. TRIAL REGISTRATION NUMBER: ChiCTR-COC-17013056.

Higher cerebral small vessel disease burden is associated with smaller hematoma volume in mixed-location intracerebral hemorrhage.

OBJECTIVE: To study the relationship between cerebral small vessel disease (CSVD) and hematoma volume in mixed-location intracerebral hemorrhage (ICH), and non-mixed ICH (hypertensive arteriopathy/cerebral amyloid angiopathy-related ICH). METHODS: We consecutively collected patients with primary ICH with MRI. Mixed-location ICH was defined as having ICH or cerebral microbleeds (CMBs) in both lobar and deep regions. CSVD markers including lacunes, white matter hyperintensities (WMH), CMBs, and enlarged perivascular spaces (EPVS) were assessed on brain MRI during hospitalization. Multivariable binary logistic regression (≥30 ml vs. <30 ml) and linear regression analyses (log-transformed hematoma volume as dependent variable) were implemented to explore the association between CSVD and hematoma volume. RESULTS: Of the 167 included patients, 69 (41.3%) had mixed-location ICH, with higher prevalence of lacune, more CMB count, higher WMH score and total CSVD score than those with non-mixed ICH (all p < .001). Higher WMH score was associated with lower risk of hematoma volume ≥30 ml (adjusted OR 0.521, 95% CI 0.299-0.908, p = .021) in patients with mixed-location ICH. Also, multivariable linear regression showed the association of smaller hematoma volume with higher CSVD burden, especially in mixed-location ICH (ß = -0.349, p = .019 for CMB ≥ 5; ß = -0.183, p < .001 for WMH score; ß = -0.456, p = .002 for EPVS>20 in basal ganglia and/or centrum semiovale; ß = -0.256, p = .002 for CSVD score), while these relationships were not observed in non-mixed ICH. CONCLUSIONS: Higher CSVD burden is associated with smaller hematoma volume in mixed-location ICH, but not in non-mixed ICH, which is novel and needs further studies with larger sample size to confirm our results and explore the underlying mechanisms.

Cerebral Small Vessel Disease Load Predicts Functional Outcome and Stroke Recurrence After Intracerebral Hemorrhage: A Median Follow-Up of 5 Years.

Background: Uncertainty exists over the long-term prognostic significance of cerebral small vessel disease (CSVD) in primary intracerebral hemorrhage (ICH). Methods: We performed a longitudinal analysis of CSVD and clinical outcomes in consecutive patients with primary ICH who had MRI. Baseline CSVD load (including white matter hyperintensities [WMH], cerebral microbleeds [CMBs], lacunes, and enlarged perivascular spaces [EPVS]) was evaluated. The cumulative CSVD score was calculated by combining the presence of each CSVD marker (range 0-4). We followed participants for poor functional outcome [modified Rankin scale [mRS] ≥ 4], stroke recurrence, and time-varying survival during a median follow-up of 4.9 [interquartile range [IQR] 3.1-6.0] years. Parsimonious and fuller multivariable logistic regression analysis and Cox-regression analysis were performed to estimate the association of CSVD markers, individually and collectively, with each outcome. Results: A total of 153 patients were included in the analyses. CMBs ≥ 10 [adjusted OR [adOR] 3.252, 95% CI 1.181-8.956, p = 0.023] and periventricular WMH (PWMH) (adOR 2.053, 95% CI 1.220-3.456, p = 0.007) were significantly associated with poor functional outcome. PWMH (adOR 2.908, 95% CI 1.230-6.878, p = 0.015) and lobar CMB severity (adOR 1.811, 95% CI 1.039-3.157, p = 0.036) were associated with stroke recurrence. The cumulative CSVD score was associated with poor functional outcome (adOR 1.460, 95% CI 1.017-2.096) and stroke recurrence (adOR 2.258, 95% CI 1.080-4.723). Death occurred in 36.1% (13/36) of patients with CMBs ≥ 10 compared with 18.8% (22/117) in those with CMB < 10 (adjusted HR 2.669, 95% CI 1.248-5.707, p = 0.011). In addition, the cumulative CSVD score ≥ 2 was associated with a decreased survival rate (adjusted HR 3.140, 95% CI 1.066-9.250, p = 0.038). Conclusions: Severe PWMH, CMB, or cumulative CSVD burden exert important influences on the long-term outcome of ICH.

Neck Circumference Is Associated With Poor Outcome in Patients With Spontaneous Intracerebral Hemorrhage.

Objective: This study aimed to assess the association between neck circumference (NC) and functional outcome in intracerebral hemorrhage (ICH) patients. Methods: We prospectively analyzed data from ICH patients who received treatment at our institution from January 2018 to November 2019. Patients were categorized into two groups according to 180-day modified Rankin scale (MRS) scores. Univariate and multivariate analyses were performed to assess whether NC was associated with poor outcome in ICH patients. Receiver operating characteristic (ROC) curve analysis was performed to determine the significance of NC in predicting the functional outcome of ICH patients. Results: A total of 312 patients were enrolled in our study. Multivariate logistic regression analysis indicated that NC was an independent predictor of poor 180-day functional outcome [odds ratio (OR) = 1.205, 95% confidence interval (CI): 1.075-1.350, p = 0.001]. ROC analysis revealed that NC could predict poor functional outcome at 6 months. Conclusions: NC is an independent predictor of unfavorable functional outcome at 6 months in ICH patients.

Total Burden of Cerebral Small Vessel Disease in Recurrent ICH versus First-ever ICH.

The relationship between recurrent intracerebral hemorrhage (ICH) and total burden of cerebral small vessel disease (CSVD) is not completely investigated. We aimed to study whether recurrent intracerebral hemorrhage (ICH) had higher CSVD score than first-ever ICH. Lacunes, white matter hyperintensities (WMH), cerebral microbleeds (CMBs), enlarged perivascular spaces (EPVS), cortical superficial siderosis (cSS) and CSVD score were rated on brain magnetic resonance imaging (MRI) in primary ICH patients. Recurrent ICHs were confirmed by reviewing the medical records and MRI scans. Mixed hematomas were defined as follows: deep + lobar, deep + cerebellar, or deep + lobar + cerebellar. Of the 184 patients with primary ICH enrolled (mean age, 61.0 years; 75.5% men), recurrent ICH was present in 45 (24.5%) patients; 26.1% (48/184) had ≥2 hematomas, 93.8% (45/48) of which exhibited recurrent ICH. Mixed hematomas were identified in 8.7% (16/184) of patients and bilateral hematomas in 17.9% (33/184). All mixed hematomas and bilateral hematomas were from cases of recurrent ICH. Patients with mixed etiology-ICH were more likely to have recurrent ICH than patients with cerebral amyloid angiopathy (CAA) or hypertensive angiopathy (HA)-related ICH (36.8% vs17.8%, p=0.008). Multivariate ordinal regression analysis showed that the presence of recurrent ICH (p=0.001), ≥2 hematomas (p=0.002), mixed hematomas (p<0.00001), and bilateral hematomas (p=0.002) were separately significantly associated with a high CSVD score. Recurrent ICH occurs mostly among patients with mixed etiology-ICH and is associated with a higher CSVD burden than first-ever ICH, which needs to be verified by future larger studies.

Serum magnesium but not calcium was associated with hemorrhagic transformation in stroke overall and stroke subtypes: a case-control study in China.

Association between serum calcium and magnesium versus hemorrhagic transformation (HT) remains to be identified. A total of 1212 non-thrombolysis patients with serum calcium and magnesium collected within 24 h from stroke onset were enrolled. Backward stepwise multivariate logistic regression analysis was conducted to investigate association between calcium and magnesium versus HT. Calcium and magnesium were entered into logistic regression analysis in two models, separately: model 1, as continuous variable (per 1-mmol/L increase), and model 2, as four-categorized variable (being collapsed into quartiles). HT occurred in 140 patients (11.6%). Serum calcium was slightly lower in patients with HT than in patient without HT (P = 0.273). But serum magnesium was significantly lower in patients with HT than in patients without HT (P = 0.007). In logistic regression analysis, calcium displayed no association with HT. Magnesium, as either continuous or four-categorized variable, was independently and inversely associated with HT in stroke overall and stroke of large-artery atherosclerosis (LAA). The results demonstrated that serum calcium had no association with HT in patients without thrombolysis after acute ischemic stroke. Serum magnesium in low level was independently associated with increasing HT in stroke overall and particularly in stroke of LAA.

Acupuncture for acute stroke.

BACKGROUND: Sensory stimulation via acupuncture has been reported to alter activities of numerous neural systems by activating multiple efferent pathways. Acupuncture, one of the main physical therapies in Traditional Chinese Medicine, has been widely used to treat patients with stroke for over hundreds of years. This is the first update of the Cochrane Review originally published in 2005. OBJECTIVES: To assess whether acupuncture could reduce the proportion of people with death or dependency, while improving quality of life, after acute ischemic or hemorrhagic stroke. SEARCH METHODS: We searched the Cochrane Stroke Group trials register (last searched on February 2, 2017), the Cochrane Central Register of Controlled Trials Ovid (CENTRAL Ovid; 2017, Issue 2) in the Cochrane Library, MEDLINE Ovid (1946 to February 2017), Embase Ovid (1974 to February 2017), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) EBSCO (1982 to February 2017), the Allied and Complementary Medicine Database (AMED; 1985 to February 2017), China Academic Journal Network Publishing Database (1998 to February 2017), and the VIP database (VIP Chinese Science Journal Evaluation Reports; 1989 to February 2017). We also identified relevant trials in the Chinese Clinical Trial Registry (last searched on Feburuary 20, 2017), the World Health Organization (WHO) International Clinical Trials Registry Platform (last searched on April 30, 2017), and Clinicaltrials.gov (last searched on April 30, 2017). In addition, we handsearched the reference lists of systematic reviews and relevant clinical trials. SELECTION CRITERIA: We sought randomized clinical trials (RCTs) of acupuncture started within 30 days from stroke onset compared with placebo or sham acupuncture or open control (no placebo) in people with acute ischemic or hemorrhagic stroke, or both. Needling into the skin was required for acupuncture. Comparisons were made versus (1) all controls (open control or sham acupuncture), and (2) sham acupuncture controls. DATA COLLECTION AND ANALYSIS: Two review authors applied the inclusion criteria, assessed trial quality and risk of bias, and extracted data independently. We contacted study authors to ask for missing data. We assessed the quality of the evidence by using the GRADE approach. We defined the primary outcome as death or dependency at the end of follow-up . MAIN RESULTS: We included in this updated review 33 RCTs with 3946 participants. Twenty new trials with 2780 participants had been completed since the previous review. Outcome data were available for up to 22 trials (2865 participants) that compared acupuncture with any control (open control or sham acupuncture) but for only six trials (668 participants) that compared acupuncture with sham acupuncture control. We downgraded the evidence to low or very low quality because of risk of bias in included studies, inconsistency in the acupuncture intervention and outcome measures, and imprecision in effect estimates.When compared with any control (11 trials with 1582 participants), findings of lower odds of death or dependency at the end of follow-up and over the long term (≥ three months) in the acupuncture group were uncertain (odds ratio [OR] 0.61, 95% confidence interval [CI] 0.46 to 0.79; very low-quality evidence; and OR 0.67, 95% CI 0.53 to 0.85; eight trials with 1436 participants; very low-quality evidence, respectively) and were not confirmed by trials comparing acupuncture with sham acupuncture (OR 0.71, 95% CI 0.43 to 1.18; low-quality evidence; and OR 0.67, 95% CI 0.40 to 1.12; low-quality evidence, respectively).In trials comparing acupuncture with any control, findings that acupuncture was associated with increases in the global neurological deficit score and in the motor function score were uncertain (standardized mean difference [SMD] 0.84, 95% CI 0.36 to 1.32; 12 trials with 1086 participants; very low-quality evidence; and SMD 1.08, 95% CI 0.45 to 1.71; 11 trials with 895 participants; very low-quality evidence). These findings were not confirmed in trials comparing acupuncture with sham acupuncture (SMD 0.01, 95% CI -0.55 to 0.57; low-quality evidence; and SMD 0.10, 95% CI -0.38 to 0.17; low-quality evidence, respectively).Trials comparing acupuncture with any control have reported little or no difference in death or institutional care at the end of follow-up (OR 0.78, 95% CI 0.54 to 1.12; five trials with 1120 participants; low-quality evidence), death within the first two weeks (OR 0.91, 95% CI 0.33 to 2.55; 18 trials with 1612 participants; low-quality evidence), or death at the end of follow-up (OR 1.08, 95% CI 0.74 to 1.58; 22 trials with 2865 participants; low-quality evidence).The incidence of adverse events (eg, pain, dizziness, faint) in the acupuncture arms of open and sham control trials was 6.2% (64/1037 participants), and 1.4% of these (14/1037 participants) discontinued acupuncture. When acupuncture was compared with sham acupuncture, findings for adverse events were uncertain (OR 0.58, 95% CI 0.29 to 1.16; five trials with 576 participants; low-quality evidence). AUTHORS' CONCLUSIONS: This updated review indicates that apparently improved outcomes with acupuncture in acute stroke are confounded by the risk of bias related to use of open controls. Adverse events related to acupuncture were reported to be minor and usually did not result in stopping treatment. Future studies are needed to confirm or refute any effects of acupuncture in acute stroke. Trials should clearly report the method of randomization, concealment of allocation, and whether blinding of participants, personnel, and outcome assessors was achieved, while paying close attention to the effects of acupuncture on long-term functional outcomes.

Kidney Dysfunction is Associated with a High Burden of Cerebral Small Vessel Disease in Primary Intracerebral Hemorrhage.

OBJECTIVES: To investigate the association of kidney function with the total burden of Cerebral Small Vessel Disease (CSVD) in primary Intracerebral Hemorrhage (pICH). METHODS: Cerebral magnetic resonance imagings of consecutively enrolled pICH patients were reviewed to assess for lacunes, White Matter Hyperintensity (WMH), Cerebral Microbleeds (CMBs) and Enlarged Perivascular Spaces (EPVS). Minor refinements to the CSVD score, namely modified CSVD score 1 and 2, were made by incorporating different weightings of CSVD markers. Kidney function was assessed using the estimated Glomerular Filtration Rate (eGFR). We used ordinal regression analysis to assess the association of kidney function with the CSVD score and modified scores. RESULTS: In the 108 patients included, the presence of lacunes, CMBs, MWH and basal ganglia EPVS>10 was 27.8%, 67.6%, 47.2% and 35.2%, respectively. In multivariable ordinal regression, a decreasing eGFR value was associated with an increased CSVD score [Odds Ratio (OR) 0.978, 95% Confidence Interval (CI) 0.962 to 0.995, P=0.013], modified CSVD score 1 (OR 0.973, 95% CI 0.957 to 0.990, P=0.002) and 2 (OR 0.969, 95% CI 0.953 to 0.986, P<0.001). The link between eGFR and the total burden of CSVD was significant in strictly deep pICH (P=0.011 for CSVD score; P=0.001 for modified score 1 and 2), but not strictly lobar pICH in subgroup analysis. CONCLUSIONS: Low eGFR is associated with a high burden of CSVD in patients with deep pICH, but not lobar pICH. Future studies are warranted to assess whether low eGFR is a potential therapeutic target for preventing the progress of CSVD burden for deep pICH.

The burden of non-symptomatic cerebral ischemia on MRI and its effect on clinical outcomes in patients with first-ever intracerebral hemorrhage.

PURPOSE: To compare the burden of non-symptomatic cerebral ischemia (NSCI) detected on magnetic resonance imaging (MRI) and computed tomography (CT), and assess the association of MRI-NSCI with clinical outcomes among patients with first-ever intracerebral hemorrhage (ICH). METHODS: Two thousand three hundred and five consecutive ICH patients admitted to our institution from May 2012 to October 2015 were retrospectively reviewed. Data on clinical characteristics and MRI/CT scans were collected during hospitalization. Information on clinical outcomes at three-month were also obtained. RESULTS: Three hundred and seventy-seven patients performed MRIs and 1966 had CTs during hospitalization. NSCI was detected in 152 (40.3%) patients with MRIs and in 638 (32.5%) with CTs. Comparing with CT, NSCI detected by MRI was more common (40.3% vs. 32.5%; P = 0.011), more likely to be multiple loci (93.4% vs. 79.6%; P < 0.001) and bilateral hemispheres (84.9% vs. 73.2%; P = 0.003). Furthermore, the presence of NSCI, multiple NSCI, bilateral NSCI and bilateral hematoma combined with bilateral NSCI were associated with poor outcomes (P < 0.001, P < 0.001, P < 0.001, P = 0.041, respectively) in univariate analysis. In multivariable logistic regression, bilateral hematoma combined with bilateral NSCI was still associated with poor outcomes (OR 3.983, 95% CI 1.172-13.539; P = 0.027). CONCLUSIONS: Compared with CT, NSCI on MRI tends to be multiple loci and located in bilateral hemispheres. The results of NSCI in ICH may be underestimated based on CT. In addition, the increased poor outcomes at three-month suggest that NSCI may play an important role in reducing clinical outcomes.

Cardiac troponin and cerebral herniation in acute intracerebral hemorrhage.

OBJECTIVES: To explore the association, if any, between the relationship between cardiac troponin and cerebral herniation after intracerebral hemorrhage (ICH). METHODS: Six hundred and eighty-seven consecutive ICH patients admitted to West China Hospital from May 1, 2014 to September 1, 2015 were retrospectively reviewed. Data on demographics, etiology, laboratory examinations at admission including serum cardiac troponin, computed tomography (CT) scans at admission and follow-up, and clinical outcomes were obtained. Using multiple logistic regression to identify the relationship of troponin and herniation. The association between troponin and hematoma volume was assessed using bivariate correlation and linear regression. RESULTS: Among 188 (27.4%) patients who underwent the test of serum cardiac troponin at admission, 16 (8.5%) demonstrated cerebral herniation. The median time from symptom onset to CT at admission and follow-up was 4 and 30.25 hr, respectively. In multivariate analysis, elevated troponin was independently associated with cerebral herniation (adjusted odds ratio [OR] 5.19; 95% confidence interval [CI], 1.08-24.93). And those with elevated troponin had larger hematoma volume at follow-up in bivariate correlation (correlation coefficient, .375, p = .003) and linear regression (ß, .370, 95% CI, 0.062-0.320, p = .005), higher National Institutes of Health Stroke Scale score (adjusted OR 2.06; 95% CI, 1.06-4.01, p = .033) and lower Glasgow Coma Scale score (adjusted OR 2.34; 95% CI, 1.17-4.68, p = .016) than those without. CONCLUSIONS: Elevated cardiac troponin was associated with an almost five-fold increased risk of cerebral herniation, but not in-hospital mortality. The possibility of cerebral herniation should be considered when ICH patients with large hematoma volume and elevated troponin.

Prognostic Significance of Intraventricular Hemorrhage in Vascular Structural Abnormality-Related Intracerebral Hemorrhage.

BACKGROUND: The prognostic significance of intraventricular hemorrhage (IVH) in patients with vascular structural abnormality-related intracerebral hemorrhage (VSARICH) is poorly understood. METHOD: We prospectively included consecutive patients diagnosed with VSARICH. Imaging of initial brain computed tomography (CT) scans within 48 hours of symptom onset was analyzed. The presence and severity of IVH were recorded. Severity of IVH was measured using the modified Graeb (mGraeb) score. Baseline characteristics and 3-month outcomes were compared between the IVH and non-IVH groups. Multivariate logistic regression was used to examine the independent association between IVH and 3-month outcomes. RESULTS: A total of 132 VSARICH patients were included for analysis, and 71 (53.8%) of them had IVH on initial CT imaging. IVH patients had a median mGraeb score of 15 (6-21), and compared to non-IVH patients, they had shorter delay to first CT scan and higher stroke severity on admission (all P ≤ .005). At 3 months, IVH patients had higher death rates (30.3% versus 7.0%; P = .001) and poor outcome rates (48.5% versus 21.1%; P = .002) than non-IVH patients. After multivariate analysis, IVH severity was associated with 3-month death (Model 1 OR 1.112, 95% CI [1.027-1.204], P = .009; Model 2 OR 1.110, 95% CI [1.027-1.200], P = .009) and poor outcome (Model 2 OR 1.053, 95% CI [1.001-1.108], P = .047), although no independent association between IVH presence and outcomes was observed. CONCLUSION: IVH severity measured by mGraeb score independently predicts death and poor functional outcome in patients with VSARICH.

Liver Function Indicators Performed Better to Eliminate Cardioembolic Stroke than to Identify It from Stroke Subtypes.

BACKGROUND: Identifying the etiology of ischemic stroke is essential to acute management and secondary prevention. The value of liver function indicators in differentiating stroke subtypes remains to be evaluated. METHODS: A total of 1333 acute ischemic stroke patients were included. Liver function indicators collected within 24 hours from stroke onset, including alanine aminotransferase, aspartate aminotransferase (AST), alkaline phosphatase, gamma-glutamyl transpeptidase (GGT), and bilirubin (BILI), were collapsed into quartiles (Q) and also dichotomized by Q1. Multivariate regression analysis was conducted to identify the independent association between liver function indicators and cardioembolic stroke (SCE). Area under the curve (AUC) of receiver operating characteristic analysis was conducted, and sensitivity (Sen), specificity (Spe), positive prospective value (PPV), and negative prospective value (NPV) were determined to evaluate the predictive value of liver function indicators for SCE. RESULTS: AST, GGT, and BILI were associated with SCE. After adjustment, only AST was related to SCE independently. The incidence of SCE in the Q1 of AST, GGT, and BILI, particularly in the Q1 of AST, was quite low. The ability of AST, GGT, and BILI to identify SCE was poor, with low AUC, Sen, and PPV. The value of AST, GGT, and BILI in eliminating SCE from stroke subtypes was good, with high Spe and moderate NPV, and was enhanced after combining each liver function indicator. CONCLUSIONS: Results of present study demonstrated that AST, GGT, and BILI, particularly AST, had a potential to eliminate SCE from stroke subtypes, and the ability of eliminating SCE would be strengthened after combining each liver function indicator together.