Increased Serum EphrinA1 Is Associated with Parenchymal Hematoma after Ischemic Stroke.

INTRODUCTION: Previous preclinical studies reported that the level of serum EphrinA1 was associated with blood-brain barrier disruption; however, its role in predicting parenchymal hematoma (PH) after ischemic stroke is underexplored. We aimed to explore the association between the level of serum EphrinA1 and PH in patients with ischemic stroke. METHODS: Patients with ischemic stroke after onset from West China Hospital, Sichuan University, were prospectively enrolled between January 2017 and December 2019. The level of serum EphrinA1 at baseline was measured after admission. PH was diagnosed as hematoma within the infarct territory detected on the brain CT/MRI scans within 7 days after onset but not on the initial scan according to European Cooperative Acute Stroke Study (ECASS) III criteria. The association between the level of serum EphrinA1 and PH after ischemic stroke was assessed by multiple logistic regression analysis. RESULTS: A total of 667 patients were included in the final analysis. The mean age was 67.20 ± 14.31 years, and 57.87% (368/667) were males. Of the 667 patients, 65 (9.75%) patients had PH. The median of EphrinA1 on admission was 82.83 ng/mL (IQR, 70.11-93.75 ng/mL). Compared with patients without PH, those with PH had a higher level of serum EphrinA1 (p = 0.024). Patients were divided into 3 categories based on EphrinA1 tertiles (T1, <79.11 ng/mL, n = 223; T2, 79.11-93.75 ng/mL, n = 222; and T3, >93.75 ng/mL, n = 222). After adjusting for age, sex, atrial fibrillation, smoking, statins, antiplatelets, Trail of Org 10172 in Acute Stroke Treatment (TOAST) classification and National Institutes of Health Stroke Scale (NIHSS) score ≥15, patients in the second and third EphrinA1 tertiles showed a significant increase in PH compared with those in the lowest tertile (OR 2.44, 95% CI: 1.10-5.40, p = 0.028; OR 2.61, 95% CI: 1.19-5.74, p = 0.017, respectively). Additionally, adjusting for reperfusion therapy (thrombolysis and/or endovascular therapy), only patients in the highest group (tertile 3) had a significantly higher risk of PH compared to the lowest group (OR 2.30, 95% CI: 1.03-5.13, p = 0.042). CONCLUSION: Higher serum EphrinA1 is independently associated with a higher risk of PH after ischemic stroke. Future studies with larger sample sizes are needed to validate our findings and elucidate the potential role of EphrinA1 in PH.

Acute Cerebral Microinfarcts in Acute Ischemic Stroke: Imaging and Clinical Significance.

BACKGROUND: Limited data exist on the significance of acute cerebral microinfarcts (A-CMIs) in the context of acute ischemic stroke (AIS). We aimed to determine the profile and prognostic significance of A-CMIs on magnetic resonance imaging (MRI) in patients presenting with AIS. METHODS: A prospective single-center series of patients with AIS who had 3T MRIs between March 2013 and December 2019. The presence, number, and location of A-CMIs on diffusion-weighted imaging, and markers of cerebral small vessel disease (CSVD), macroinfarcts features, and etiology were classified as cardioembolism (CE) or large artery atherosclerosis (LAA) or none. RESULTS: Among 273 patients, A-CMIs were detected in 130 patients (47.6%), of whom cortical A-CMIs were found in 95 (73.0%) patients. Patients with A-CMIs were significantly older, less likely to have diabetes mellitus, and more likely to have atrial fibrillation and an embolic source (CE or LAA) compared to other patients. Patients with A-CMI had a higher frequency of macroinfarcts (diameter >20 mm), more often multiple and distributed in single or multiple vessel territories than other patients. An embolic source (LAA or CE) was independently associated with cortical A-CMIs (LAA adjusted odds ratio [aOR] 4.0 95% confidence interval [CI] 1.6-9.5; CE aOR 2.5, 95% CI 1.1-5.6), whereas lacunes were independently related to subcortical A-CMIs (aOR 2.6, 95% CI 1.2-5.8). CONCLUSIONS: We have shown A-CMIs occur in cortical and subcortical regions in nearly half of AIS patients, where microembolism and CSVD are, respectively, the key presumed etiological mechanism.

Retinal microvasculature and cerebral hemodynamics in patients with internal carotid artery stenosis.

PURPOSE: To investigate the relationship between retinal microvasculature and cerebral hemodynamics in patients with internal carotid artery (ICA) stenosis. METHODS: Patients with unilateral moderate or severe ICA stenosis(≥50%) from West China hospital, Sichuan university were consecutively and prospectively recruited enrolled in the current study. En face angiograms of the superficial vascular complex (SVC), deep vascular complex (DVC), superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP) were generated by automatic segmentation using swept-source optical coherence tomography angiography (SS-OCTA) to assess the retinal microvascular perfusion. The cerebral blood flow perfusion on bilateral middle cerebral artery territories measured at the basal ganglia level was assessed by brain computed tomography perfusion (CTP). CTP data were postprocessed to generate maps of different perfusion parameters including cerebral blood flow (CBF), cerebral blood volume (CBV), time to peak (TTP), mean transit time (MTT) and permeability surface(PS). Relative perfusion parameters (rPS, rCBF, etc.) were calculated as the ratio of the value on the contralateral side to that on the ipsilateral side. RESULTS: In the final analysis, 31 patients were included, of whom 11 patients had a moderate ICA stenosis (50-69%) and 20 with a severe ICA stenosis(≥70%). A total of 55 eyes were analyzed in the study, 27 eyes from the ipsilateral side (ie, side with stenosis) and 28 eyes from the contralateral side. In the patients with ICA stenosis, there was a strong correlation between the retinal microvascular perfusion of SVC with rCBV(B = 0.45, p = 0.03), rCBF(B = 0.26, p = 0.02) and rPS(B = 0.45, p < 0.001) after adjustment for age, sex and vascular risk factors. Similar correlations were also found between microvasculature in SVP and cerebral perfusion changes. There were no any significant associations of microvascular perfusion in both DVC and DCP with CTP parameters(all p > 0.05). CONCLUSIONS: Retinal perfusion changes in superficial vascular layer (SVC and SVP) were correlated with brain hemodynamic compromise in patients with unilateral moderate or severe ICA stenosis(≥50%). Given the limited size of our study, future studies with larger sample size are needed to confirm our findings.

Clinical features and imaging markers of small vessel disease in symptomatic acute subcortical cerebral microinfarcts.

BACKGROUND: As currently defined, recent small subcortical infarcts (RSSI) do not have a lower size boundary, and the smallest diffusion-weighted imaging (DWI) infarcts, which we term acute subcortical cerebral microinfarcts (As-CMI) with lesion diameter less than 5 mm, might have clinical implications distinct from RSSI. We aimed to investigate the distinct characteristics of As-CMI as compared to the larger size of RSSI regarding vascular risk factors, clinical manifestation, radiological markers of SVD distribution, and outcomes. METHODS: In a consecutive cohort, patients were selected with a magnetic resonance DWI-confirmed RSSI between January 2010 and November 2020. We measured axial infarct diameter and classified patients into two groups: The As-CMI group (diameter < 5 mm) versus the Larger RSSI group (diameter 5-20 mm). Clinical variables, including vascular risk factors, clinical symptoms/signs, lesion locations, and radiological markers of cerebral small vessel disease (SVD) on MRI were analyzed between the two groups. Patients were followed up for 12 months and functional outcomes were measured by the modified ranking scale (mRS). RESULTS: In a total of 584 patients with RSSI, 23 (3.9%) were defined as As-CMI. The most common neurological deficits with As-CMI were hemiparalysis (n = 20), followed by central facial/lingual palsy (n = 10) and hemidysesthesia (n = 10). Most As-CMIs were located in the basal ganglia (n = 11), followed by the thalamus (n = 5) and centrum semiovale (n = 4). No different regional distributions and symptoms/signs frequencies were found between the two groups except for a lower percentage of dysarthria in the As-CMI group (p = 0.008). In a multivariate analysis, patients with As-CMI were independently associated with the presence of lacunes (adjusted odds ratio [aOR] 2.88; 95% confidence interval [CI] 1.21-6.84), multiple lacunes (aOR 3.5, CI 1.29-9.48) and higher total SVD burden (aOR 1.68, CI 1.11-2.53). Patients with As-CMI did not show a better functional outcome after 12 months of follow-up. CONCLUSIONS: Patients with As-CMI had a non-specific clinical profile but a higher burden of SVD, indicating As-CMI might be s sign of more severe small vascular injury. Whether its vascular features are associated with worse cognitive outcomes requires further investigation.

Liver fibrosis indices associated with substantial hematoma expansion in Chinese patients with primary intracerebral hemorrhage.

BACKGROUND: Whether liver fibrosis is associated with increased risk for substantial hematoma expansion (HE) after intracerebral hemorrhage (ICH) is still uncertain. We evaluated the association between various liver fibrosis indices and substantial HE in a Chinese population with primary ICH. METHODS: Primary ICH patients admitted to West China Hospital within 24 h of onset between January 2015 and June 2018 were consecutively enrolled. Six liver fibrosis indices were calculated, including aspartate aminotransferase (AST)-platelet ratio index (APRI), AST/alanine aminotransferase ratio-platelet ratio index (AARPRI), fibrosis-4 (FIB-4), modified fibrosis-4 (mFIB-4), fibrosis quotient (FibroQ) and Forns index. Substantial HE was defined as an increase of more than 33% or 6 mL from baseline ICH volume. The association of each fibrosis index with substantial HE was analyzed using binary logistic regression. RESULTS: Of 436 patients enrolled, about 85% showed largely normal results on standard hepatic assays and coagulation parameters. Substantial HE occurred in 115 (26.4%) patients. After adjustment, AARPRI (OR 1.26, 95% CI 1.00-1.57) and FIB-4 (OR 1.15, 95% CI 1.02-1.30) were independently associated with substantial HE in ICH patients within 24 h of onset, respectively. In ICH patients within 6 h of onset, each of the following indices was independently associated with substantial HE: APRI (OR 2.64, 95% CI 1.30-5,36), AARPRI (OR 1.55, 95% CI 1.09-2.21), FIB-4 (OR 1.35, 95% CI 1.08-1.68), mFIB-4 (OR 1.09, 95% CI 1.01-1.18), FibroQ (OR 1.08, 95% CI 1.00-1.16) and Forns index (OR 1.37, 95% CI 1.10-1.69). CONCLUSIONS: Liver fibrosis indices are independently associated with higher risk of substantial HE in Chinese patients with primary ICH, which suggesting that subclinical liver fibrosis could be routinely assessed in such patients to identify those at high risk of substantial HE.

[The Monitoring and Application of Transcranial Doppler Ultrasound in Patients with Severe Neurovascular Diseases].

OBJECTIVE: To investigate the monitoring effect and application of transcranial Doppler ultrasound (TCD) in patients with severe neurovascular cerebrovascular diseases. METHODS: From December 2016 to October 2018, 96 patients with cerebrovascular disease in Department of Neurology and ICU, West China Hospital, Sichuan University were monitored by bedside TCD, including the detection of bilateral middle cerebral arteries (MCAs) through temporal window, and the detection of the basilar artery (BA) through occipital window, characterized by the peak systolic blood flow velocity, peak diastolic blood flow velocity, average peak blood flow velocity, vascular pulsatility index, vascular pulsatility index, vascular resistance index and blood flow spectrum morphology in local hemodynamic changes. According to the monitoring results, it was divided into vasospasm group, increased blood flow group and insufficient blood supply group. Relevant data of monitoring results were analysed. RESULTS: Bedside TCD monitoring was successfully used to all cerebrovascular diseases patients. Among 96 patients, 37 patients (38.54%) had increased cerebral blood flow, 15 patients (15.62%) had cerebral vasospasm, and 93 patients had insufficient cerebral blood supply (90.62%, including insufficient blood supply to the MCA and BA). Patients mainly with cerebral aneurysm and hypertensive intracerebral hemorrhage types contributed the highest proportion of insufficient blood supply, followed by the increase of blood flow, and the incidence of vasospasm was relatively low. In cerebral aneurysm group and hypertensive intracerebral hemorrhage group, and differences in the incidence of insufficient blood supply, increased blood flow, and vasospasm were statistically significant ( P<0.05). CONCLUSION: The bedside TCD monitoring can assess the patient's craniocerebral hemodynamic information and provide a clinical guidance.

Early consciousness disorder in acute ischemic stroke: incidence, risk factors and outcome.

BACKGROUND: Little is known about the incidence and risk factors of early consciousness disorder (ECD) in patients with acute ischemic stroke, or about how ECD may affect complications and outcomes. METHODS: Patients admitted to our hospital within 24 h of onset of acute ischemic stroke were consecutively enrolled. ECD was evaluated clinically and using the Glasgow coma scale. Multivariate analysis was used to identify risk factors of ECD, as well as associations between ECD and clinical outcomes. RESULTS: Of the 569 patients enrolled, 199 (35 %) had ECD. Independent risk factors of ECD were advanced age (OR 1.027, 95 % CI 1.007 to 1.048), National Institutes of Health Stroke Score on admission (OR 1.331, 95 % CI 1.257 to 1.410), and massive cerebral infarct (OR 3.211, 95 % CI 1.642 to 6.279). ECD was associated with higher frequency of stroke-related complications (83.4 % vs. 31.1 %, P < 0.001) and higher in-hospital mortality (17.1 % vs. 0.5 %, P < 0.001). ECD independently predicted 3-month death/disability (OR 3.272, 95 % CI 1.670 to 6.413). CONCLUSIONS: ECD is prevalent in Chinese patients with acute ischemic stroke. Risk factors include advanced age, stroke severity, and massive cerebral infarct. ECD is associated with higher frequency of stroke-related complications and 3-month death/disability.

Fibrates for secondary prevention of cardiovascular disease and stroke.

BACKGROUND: Fibrates are a class of drugs characterised by mainly lowering high triglyceride, raising high-density lipoprotein (HDL) cholesterol, and lowering the small dense fraction of low-density lipoprotein (LDL) cholesterol. Their efficacy for secondary prevention of serious vascular events is unclear, and to date no systematic review focusing on secondary prevention has been undertaken. OBJECTIVES: To assess the efficacy and safety of fibrates for the prevention of serious vascular events in people with previous cardiovascular disease (CVD), including coronary heart disease and stroke. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 9, 2014) on the Cochrane Library, MEDLINE (OVID, 1946 to October week 1 2014), EMBASE (OVID, 1980 to 2014 week 41), the China Biological Medicine Database (CBM) (1978 to 2014), the Chinese National Knowledge Infrastructure (CNKI) (1979 to 2014), Chinese Science and Technique Journals Database (VIP) (1989 to 2014). We also searched other resources, such as ongoing trials registers and databases of conference abstracts, to identify further published, unpublished, and ongoing studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in which a fibrate (for example gemfibrozil, fenofibrate) was compared with placebo or no treatment. We excluded RCTs with only laboratory outcomes. We also excluded trials comparing two different fibrates without a placebo or no-treatment control. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, assessed risk of bias, and extracted the data. We contacted authors of trials for missing data. MAIN RESULTS: We included 13 trials involving a total of 16,112 participants. Eleven trials recruited participants with history of coronary heart disease, two trials recruited participants with history of stroke, and one trial recruited participants with a mix of people with CVD. We judged overall risk of bias to be moderate. The meta-analysis (including all fibrate trials) showed evidence for a protective effect of fibrates primarily compared to placebo for the primary composite outcome of non-fatal stroke, non-fatal myocardial infarction (MI), and vascular death (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.83 to 0.94; participants = 16,064; studies = 12; I(2) = 45%, fixed effect). Fibrates were moderately effective for preventing MI occurrence (RR 0.86, 95% CI 0.80 to 0.93; participants = 13,942; studies = 10; I(2) = 24%, fixed effect). Fibrates were not effective against all-cause mortality (RR 0.98, 95% CI 0.91 to 1.06; participants = 13,653; studies = 10; I(2) = 23%), death from vascular causes (RR 0.95, 95% CI 0.86 to 1.05; participants = 13,653; studies = 10; I(2) = 11%, fixed effect), and stroke events (RR 1.03, 95% CI 0.91 to 1.16; participants = 11,719; studies = 6; I(2) = 11%, fixed effect). Excluding clofibrate trials, as the use of clofibrate was discontinued in 2012 due to safety concerns, the remaining class of fibrates were no longer effective in preventing the primary composite outcome (RR 0.90, 95% CI 0.79 to 1.03; participants = 10,320; studies = 7; I(2) = 50%, random effects). However, without clofibrate data, fibrates remained effective in preventing MI (RR 0.85, 95% CI 0.76 to 0.94; participants = 8304; studies = 6; I(2) = 47%, fixed effect). There was no increase in adverse events with fibrates compared to control. Subgroup analyses showed the benefit of fibrates on the primary composite outcome to be consistent irrespective of age, gender, and diabetes mellitus. AUTHORS' CONCLUSIONS: Moderate evidence showed that the fibrate class can be effective in the secondary prevention of composite outcome of non-fatal stroke, non-fatal MI, and vascular death. However, this beneficial effect relies on the inclusion of clofibrate data, a drug that was discontinued in 2002 due to its unacceptably large adverse effects. Further trials of the use of fibrates in populations with previous stroke and also against a background treatment with statins (standard of care) are required.

Etiology and Risk Factors of Posterior Circulation Infarction Compared with Anterior Circulation Infarction.

BACKGROUND: Many clinicians regard posterior circulation infarction (PCI) as different from anterior circulation infarction (ACI), leading them to apply different treatments. Few studies have validated this practice by directly comparing the etiology and risk factors of PCI and ACI. METHODS: We compared the etiology and risk factors of 2245 consecutive patients with a diagnosis of PCI or ACI confirmed by magnetic resonance imaging in the Chengdu Stroke Registry. Stroke etiology in each patient was classified according to Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. RESULTS: Our sample included 482 patients (21.5%) with PCI and 1763 (78.5%) with ACI. The most frequent etiology for both infarction types was small-artery occlusion, occurring in 37.6% of patients with PCI and 37.1% of those with ACI. Cardioembolism caused infarction in a significantly smaller proportion of patients with PCI (5.4%) than in patients with ACI (13.3%; odds ratio [OR] = .373; 95% confidence interval [CI], .245-.566). Frequencies of other stroke etiologies were similar between the 2 patient groups. Analysis of risk factor frequencies in the 2 groups showed hypertension to be the most common, occurring in 47.9% of patients in either group. Multivariable analysis identified 2 factors as conferring greater risk of PCI than ACI: male gender (OR = 1.392; 95% CI, 1.085-1.786) and diabetes mellitus (OR = 1.667; 95% CI, 1.275-2.180). The same analysis identified 2 factors as conferring greater risk of ACI: atrial fibrillation (OR = .530; 95% CI, .295-.951) and heart valve disease (OR = .433; 95% CI, .203-.922). Frequencies of other possible risk factors were similar between the 2 groups. CONCLUSIONS: These findings suggest that PCI and ACI are more similar than different in their etiology and risk factors and that the 2 types of infarction should be treated based more on etiology and risk factors than on their posterior or anterior localization.

A comparative study of fractional anisotropy measures and ICH score in predicting functional outcomes after intracerebral hemorrhage.

BACKGROUND: Improved prognostication during the acute phase of intracerebral hemorrhage (ICH) could influence goals of care. We investigated the utility of diffusion tensor imaging (DTI)-derived data obtained during the acute phase of ICH in predicting outcome, compared with the ICH score. METHODS: We measured fractional anisotropy (FA) values in 5 slices below the level of the lesion on the affected and unaffected corticospinal tracts (CST) and in the cerebral peduncles (CPs) in 32 patients with supratentorial ICH who had DTI MRI within 4 days after ictus. We calculated the FA ratio (rFA = FAaffected side/FAunaffected side), and examined the value of the ICH score and rFA in predicting functional outcome assessed by modified Ranking Scale (mRS) at follow-up, using ROC analyses. RESULTS: The rFA values at the CPs level, but not the 5 slices below the lesion, were significantly lower in the group with poor functional outcome (defined as mRS > 2) than in those with good functional outcome (0.96 ± 0.14 vs. 0.99 ± 0.08, p = 0.025). The ICH score had greater areas under ROC curve in predicting functional outcome compared to the mean rFA (AUC 0.74 vs. 0.44; p = 0.01 for mRS > 2; and 0.84 vs. 0.40; p < 0.001 for mRS > 3). CONCLUSIONS: The prognostic value of the ICH score surpassed that of DTI-derived data during the acute phase of ICH in this cohort of patients. Prospective and larger studies are needed to validate our findings and to assess the prognostic role of various DTI-derived measures at different times following ICH.

High blood pressure on admission in relation to poor outcome in acute ischemic stroke with intracranial atherosclerotic stenosis or occlusion.

BACKGROUND: Intracranial atherosclerotic stenosis is common in Asian, black, and Hispanic individuals. However, the management of blood pressure (BP) in the setting of acute stage in these patients is controversial. The present study aims to explore the relationship between BP on admission and outcomes in acute ischemic stroke patients with intracranial atherosclerotic stenosis or occlusion. METHODS: We prospectively registered consecutive cases of acute ischemic stroke from September 01, 2009, to August 31, 2011. Patients with severe intracranial stenosis or occlusion were included. Death or disability was followed up at the end of the third month. The multivariate logistic regression model was used to analyze the relationship between BP on admission and clinical outcomes. RESULTS: We included 215 cases, which accounted for 22.7% (215 of 946) of the total registered cases. The mean age was 60.44±13.23 years. The median time of symptoms onset to admission was 72 hours (2-270 hours). Patients with systolic blood pressure (SBP) of 120-159 mm Hg or diastolic BP of 70-89 mm Hg had the lowest death or disability. After adjustment of confounders, SBP of 160 mm Hg or more on admission was the independent predictor of death or disability at the third month (relative risk [RR], 2.89; 95% confidence interval [CI], 1.20-6.91). SBP less than 120 mm Hg on admission had a trend of increasing death or disability (RR, 1.96; 95% CI, .60-6.33). CONCLUSIONS: Higher BP on admission was associated with an increased risk of death or disability in patients with symptomatic intracranial artery stenosis or occlusion. It is reasonable that further studies on the effects of BP lowering in acute stroke include these patients.

Retinal Ischemic Perivascular Lesion Reflects Cerebral Small Vessel Disease Burden in Single Subcortical Infarction.

BACKGROUND: Retinal ischemic perivascular lesions (RIPLs) are an indicator of ischemia in the middle retina. We aimed to determine the relationship between RIPLs and single subcortical infarction (SSI). We also investigated the differences in cerebral small vessel disease imaging burden between groups with and without RIPLs in SSI. METHODS AND RESULTS: In this case-control study, we enrolled 82 patients with SSI and 72 nonstroke controls. All participants underwent magnetic resonance imaging and swept-source optical coherence tomography/optical coherence tomography angiography. Small vessel disease markers such as lacunes, cerebral microbleeds, white matter hyperintensity, and perivascular spaces were rated on brain imaging. RIPLs were assessed via swept-source optical coherence tomography. Optical coherence tomography angiography was used to measure the superficial vascular complex and deep vascular complex of the retina. After adjusting for risk factors, the presence of RIPLs was significantly associated with SSI (odds ratio [OR], 1.506 [95% CI, 1.365-1.662], P<0.001). Eyes with RIPLs showed lower deep vascular complex density (P=0.035) compared with eyes without RIPLs in patients with SSI. After adjusting for vascular risk factors, the presence of RIPLs in patients with SSI was associated with an increased periventricular white matter hyperintensity burden (ß=0.414 [95% CI, 0.181-0.647], P<0.001) and perivascular spaces-basal ganglia (ß=0.296 [95% CI, 0.079-0.512], P=0.008). CONCLUSIONS: RIPLs are associated with SSI independent of underlying risk factors. The relationship between the presence of RIPLs and small vessel disease markers provides evidence that RIPLs might be an additional indicator of cerebral ischemic changes.

Distinct alterations of retinal structure between thalamic and extra-thalamic subcortical infarction patients: A cross-sectional and longitudinal study.

AIMS: Cerebrovascular lesions in the primary visual cortex, the lateral geniculate nucleus, and the optic tract have been associated with retinal neurodegeneration via the retrograde degeneration (RD) mechanism. We aimed to use optical coherence tomography (OCT) to assess the effects of the strategic single subcortical infarction (SSI) location on retinal neurodegeneration and its longitudinal impacts. METHODS: Patients with SSI were enrolled and stratified by lesion location on cerebral MRI into the thalamic infarction group and extra-thalamic infarction group. Healthy controls from the native communities were also recruited. Retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) were quantified using OCT. Generalized estimating equation (GEE) models were used for cross-sectional analyses and linear mixed models for longitudinal analyses. P < 0.05 was considered statistically significant. RESULTS: We included a total of 283 eyes from 149 SSI patients. Of these, 115 eyes of 60 patients with follow-up were included in the longitudinal analyses. Cross-sectionally, thalamic-infarction patients had reduced retinal thickness compared with extra-thalamic infarction patients after adjustment for age, gender, disease duration, and vascular risk factors (p = 0.026 for RNFL, and p = 0.026 for GCIPL). Longitudinally, SSI patients showed greater retinal thinning compared with healthy controls over time (p = 0.040 for RNFL, and p < 0.001 for GCIPL), and thalamic infarction patients exhibited faster rates of GCIPL thinning in comparison with extra-thalamic infarction patients (p < 0.001). CONCLUSION: Our study demonstrates a distinct effect of subcortical infarction lesion site on the retina both at the early stage of disease and at the 1-year follow-up time. These results present evidence of significant associations between strategic infarction locations and retinal neurodegeneration. It may provide novel insights for further research on RD in stroke patients and ultimately facilitate individualized recovery therapeutic strategy.

Association between functional network connectivity, retina structure and microvasculature, and visual performance in patients after thalamic stroke: An exploratory multi-modality study.

BACKGROUND AND OBJECTIVE: Neuro-ophthalmologic symptoms and retinal changes have been increasingly observed following thalamic stroke, and there is mounting evidence indicating distinct alterations occurring in the vision-related functional network. However, the intrinsic correlations between these changes are not yet fully understood. Our objective was to explore the altered patterns of functional network connectivity and retina parameters, and their correlations with visual performance in patients with thalamic stroke. METHODS: We utilized resting-state functional MRI to obtain multi-modular functional connectivity (FC), and optical coherence tomography-angiography to measure various retina parameters, such as the retinal nerve fiber layer (RNFL), ganglion cell-inner plexiform layer (GCIPL), superficial vascular complex (SVC), and deep vascular complex. Visual acuity (VA) was used as a metric for visual performance. RESULTS: We included 46 patients with first-ever unilateral thalamic stroke (mean age 59.74 ± 10.02 years, 33 males). Significant associations were found between FC of attention-to-default mode and SVC, RNFL, and GCIPL, as well as between FC of attention-to-visual and RNFL (p < .05). Both RNFL and GCIPL exhibited significant associations with FC of visual-to-visual (p < .05). Only GCIPL showed an association with VA (p = .038). Stratified analysis based on a disease duration of 6 months revealed distinct and significant linking patterns in multi-modular FC and specific retina parameters, with varying correlations with VA in each subgroup. CONCLUSION: These findings provide valuable insight into the neural basis of the associations between brain network dysfunction and impaired visual performance in patients with thalamic stroke. Our novel findings have the potential to inform future targeted and individualized therapies. However, further comprehensive studies are necessary to validate our results.

Association between cerebral microbleeds and cognitive function: a systematic review.

BACKGROUND: Cerebral microbleeds (MBs), defined as haemorrhagic microvascular lesions or microangiopathy in the brain, have traditionally been considered clinically silent. Recent studies, however, suggest that MBs are associated with a decline in cognitive function. OBJECTIVE: To determine whether an association between MBs and cognitive function exists, we conducted a systematic review of the literature using the Cochrane Library, MEDLINE, EMBASE and the China National Knowledge Infrastructure database. We also searched the reference lists of relevant studies and review articles. RESULTS: A total of seven studies were included. Qualitative meta-analysis of two studies suggested that the presence of MBs was significantly associated with cognitive impairment, while quantitative meta-analysis revealed an association between MBs and cognitive dysfunction in two studies (OR 3.06, 95% CI1.59 to 5.89) and implicated MBs as important in cognitive function decline in three other studies (standardised mean difference -1.06, 95% CI -2.10 to -0.02). MBs in the frontal or temporal region and the basal ganglia might also be related to cognitive dysfunction. CONCLUSIONS: These results suggest that rather than being clinically silent, cerebral MBs might be a factor inducing cognitive function decline.

Etiologic subtype predicts outcome in mild stroke: prospective data from a hospital stroke registry.

BACKGROUND: Few studies on whether etiologic subtype can predict outcome in mild stroke are available. The study aim to explore the effect of different etiologic subtype on prognosis of these patients. METHODS: We prospectively registered consecutive cases of acute ischemic stroke from September. 01, 2009 to August. 31, 2011. Patients with National Institute of Health Stroke Scale (NIHSS) ≦3 and within 30 days of symptom onset were included. All cause death or disability (defined as modified Rankin Scale >2) were followed up at 3 months. The multivariate logistical regression model was used to analyse relationship between etiologic subtype and clinical outcomes. RESULTS: We included 680 cases, which accounted for 41.1% (680/1655) of the total registered cases. Mean age were 62.54 ± 13.51 years, and males were 65.4%. The median time of symptoms onset to admission was 72 hours. 3.8% (26/680) of cases admitted within 3 hours and 4.7% (32/680) admitted within 4.5 hours. However, no patient received intravenous thrombolysis. Of included patients, 21.5% large-artery atherosclerosis, 40.6% small-vessel disease, 7.5% cardioembolisms, 2.2% other causes and 28.2% undetermined causes. The rate of case fatality and death/disability was 2.2% and 10.1% respectively at 3 months. After adjustment of potential confounders, such as age, sex, NIHSS on admission and vascular risk factors et al., cardioembolism (RR = 3.395;95%CI 1.257 ~ 9.170) was the predictor of death or disability at 3 months and small vessel occlusion (RR = 0.412;95%CI 0.202 ~ 0.842) was the protective factor of death or disability at 3 months. CONCLUSION: Different etiologic subtype can predict the outcome in patients with mild stroke and it can help to stratify these patients for individual decision-making.

Systematic review and meta-analysis of the efficacy of sphingosine-1-phosphate (S1P) receptor agonist FTY720 (fingolimod) in animal models of stroke.

BACKGROUND AND PURPOSE: FTY720 (fingolimod) is a known sphingosine-1-phosphate (S1P) receptor agonist, which has been used in clinical trials for treating multiple sclerosis, renal transplantation, and decreasing reperfusion injury in heart, liver, and kidney. Most of these clinical trials have showed a positive effect. Especially, the trials of MS showed a reduction of relapse rate in FTY720-treated patients. Now, some animal experiments indicated that FTY720 could be a new compound available treatment for stroke patients by exerting neuroprotection via S1P1 mediated antiapoptotic mechanisms. Whether it could be effective in animals is unclear, so we conducted a systematic review to make it clear. METHODS: We conducted a systematic review and meta-analysis of the efficacy of FTY720 in animal models of focal cerebral ischemia by electronic and manual searches of the literature. Data on study quality, FTY720 dose, time of administration, and outcome measured as infarct volume or functional deficit were extracted. Data from all studies were analyzed by means of a standardized mean difference meta-analysis. RESULTS: Of the 19 identified studies, 9 were included. Among all the included studies, 178 animals were calculated for infarct size and 194 animals were assessed of neurological deficits. The methodological quality of the studies ranged from 2 to 10 according to a published 11-item quality scale. Of the nine studies selected, only one reported a negative result of FTY720. The result indicated that FTY720 reduced the infarct volume (SMD = -1.31, 95% CI -1.99 to -0.63) and improve the functional outcome (SMD = -1.61, 95% CI -2.17 to -1.05). CONCLUSIONS: The data we included supporting FTY720 was a candidate drug for stroke, but it should be considered with caution. More good quality experimental studies should be performed to evaluate the safety of FTY720 in the future. Whether FTY720 is effective in aged animals that mimicked human with comorbidities like diabetes and hypertension should also be deliberated.

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.

Retinal microvascular and structural changes in intracranial hypertension patients correlate with intracranial pressure.

AIMS: We aimed to evaluate the retinal microvascular and structural changes in intracranial hypertension (IH) patients compared with an age- and sex-matched control group. We also investigated the association between clinical parameters and retinal changes in IH patients. METHODS: Intracranial hypertension patients were divided into eyes with papilledema (IH-P) and eyes without papilledema (IH-WP). IH patients underwent lumbar puncture to measure intracranial pressure (ICP); visual acuity was performed using the Snellen chart. Optical coherence tomography (OCT) was used to image and measure the retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) while OCT angiography was used to image and measure the superficial vascular complex (SVC) and deep vascular complex (DVC). RESULTS: Intracranial hypertension patients showed reduced microvascular densities and thinner retinal thicknesses compared with the control group (all p < 0.001). Compared with the control group, IH-P showed reduced microvascular densities and thinner retinal thicknesses (all p < 0.001). IH-P showed reduced SVC density and thinner retinal thicknesses when compared with IH-WP (p = 0.008 for SVC, p = 0.025 for RNFL, and p = 0.018 for GCIPL). ICP correlated with the microvascular densities and GCIPL thickness in IH patients (p = 0.025 for GCIPL, p = 0.004 for SVC, and p = 0.002 for DVC). A significant association of ICP with SVC (p = 0.010) and DVC (p = 0.005) densities were also found in IH-P. CONCLUSIONS: Given the observed differences in these noninvasive retinal imaging markers, further research into their clinical utility in IH is needed.

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.