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There are many causes of bilateral thalamic lesions, but few cases of dural arteriovenous fistula (DAVF) associated with such lesions have been reported previously. Here, we describe an adult man with reversible rapid progressive dementia (RPD) in whom bilateral thalamic lesions were caused by a DAVF that had six supply arteries and drained into both the venous sinus and cortical veins. A 53-year-old man presented with memory decline and abnormal behavior. Head computed tomography (CT) revealed insignificant low density in the bilateral thalami and high density in the right occipital lobe. Brain magnetic resonance imaging showed hyperintensities in the thalami on T2-weighted images. Magnetic resonance venogram revealed no sign of the straight sinus, but multiple tortuous vessels in the cistern of the vein of Galen. Digital subtraction angiography revealed DAVFs near the tentorium cerebelli draining into the vein of Galen, which caused the vasogenic oedema of the thalami. The patient was then treated by transarterial embolization of the feeders. He gradually recovered after the surgery. RPD with bithalamic lesions caused by DAVF is rare but reversible. Therefore, the early recognition and intervention of DAVFs is crucial for the good prognosis of patients so that fistulas can be embolized in time.

Chronic cerebral hypoperfusion, a major vascular contributor to vascular cognitive impairment and dementia, can exacerbate small vessel pathology. Connexin43, the most abundant gap junction protein in brain tissue, has been found to be critically involved in the pathological changes of vascular cognitive impairment and dementia caused by chronic cerebral hypoperfusion. However, the precise mechanisms underpinning its role are unclear. We established a mouse model via bilateral common carotid arteries stenosis on connexin43 heterozygous male mice and demonstrated that connexin43 improves brain blood flow recovery by mediating reparative angiogenesis under chronic cerebral hypoperfusion, which subsequently reduces the characteristic pathologies of vascular cognitive impairment and dementia including white matter lesions and irreversible neuronal injury. We additionally found that connexin43 mediates hypoxia inducible factor-1α expression and then activates the PKA signaling pathway to regulate vascular endothelial growth factor-induced angiogenesis. All the above findings were replicated in bEnd.3 cells treated with 375 µM CoCl2 in vitro. These results suggest that connexin 43 could be instrumental in developing potential therapies for vascular cognitive impairment and dementia caused by chronic cerebral hypoperfusion.

Stroke is the leading cause of adult disability and death worldwide. Mitochondrial dysfunction has been recognized as a marker of neuronal death during ischemic stroke. Maintaining the function of mitochondria is important for improving the survival of neurons and maintaining neuronal function. Damaged mitochondria induce neuronal cell apoptosis by releasing reactive oxygen species (ROS) and pro-apoptotic factors. Mitochondrial fission and fusion processes and mitophagy are of great importance to mitochondrial quality control. This paper reviews the dynamic changes in mitochondria, the roles of mitochondria in different cell types, and related signaling pathways in ischemic stroke. This review describes in detail the role of mitochondria in the process of neuronal injury and protection in cerebral ischemia, and integrates neuroprotective drugs targeting mitochondria in recent years, which may provide a theoretical basis for the progress of treatment of ischemic stroke. The potential of mitochondrial-targeted therapy is also emphasized, which provides valuable insights for clinical research.

Alzheimer's disease (AD), a progressive neurodegenerative disorder, is a leading global health concern for individuals and society. However, the potential mechanisms underlying the pathogenesis of AD have not yet been elucidated. Currently, the most widely acknowledged hypothesis is amyloid cascade owing to the brain characteristics of AD patients, including great quantities of extracellular β-amyloid (Aβ) plaques and intracellular neurofibrillary tangles (NFTs). Nevertheless, the amyloid cascade hypothesis cannot address certain pathologies that precede Aβ deposition and NFTs formation in AD, such as aberrant calcium homeostasis, abnormal lipid metabolism, mitochondrial dysfunction and autophagy. Notably, these earlier pathologies are closely associated with mitochondria-associated membranes (MAMs), the physical structures connecting the endoplasmic reticulum (ER) and mitochondria, which mediate the communication between these two organelles. It is plausible that MAMs might be involved in a critical step in the cascade of earlier events, ultimately inducing neurodegeneration in AD. In this review, we focus on the role of MAMs in the regulation of AD pathologies and the potential molecular mechanisms related to MAM-mediated pathological changes in AD. An enhanced recognition of the preclinical pathogenesis in AD could provide new therapeutic strategies, shifting the modality from treatment to prevention.

Background Extraventricular neurocytoma (EVN) is a rare neurocytoma occurring in the brain parenchyma outside the ventricular system that shares similar biological behaviors and histopathologic characteristics with central neurocytoma. Reports of EVN localized in the brainstem and cerebellum are relatively uncommon. In addition, few cases with radiotherapy as the only treatment have been reported and their outcomes were unclear. Case Description We report a case of pathologically confirmed EVN of the brainstem and cerebellum in a 43-year-old male who presented with unprovoked nausea and dizziness. The patient received radiotherapy only and showed a favorable outcome during the 2-year follow-up period. Conclusions These results suggest that patients with EVN who are treated with radiotherapy without surgery may have a favorable prognosis.

Background and Purpose: There is limited information on symptomatic intracranial hemorrhage (sICH) in stroke patients without thrombolysis. This study aimed to evaluate the risk factors of sICH and the association between sICH and the prognosis at 3 and 12 months in acute ischemic stroke patients without thrombolysis.Methods: Data originated from the Chinese Acute Ischemic Stroke Treatment Outcome Registry. Univariate analysis and multivariate logistic regression were used to screen the risk factors of sICH. Multivariable logistic regression models were used to assess the association of sICH with poor outcome and all-cause mortality.Results: Totally, 9,484 patients were included, of which 69 (0.73%) had sICH. Atrial fibrillation (odds ratio [OR], 3.682; 95% confidence interval [CI], 1.945–6.971; p < 0.001), history of tumors (OR, 2.956; 95% CI, 1.115–7.593; p = 0.024), and the National Institutes of Health Stroke Scale (NIHSS) score on admission ([6–15: OR, 2.344; 95% CI, 1.365–4.024; p = 0.002] [>15: OR, 4.731; 95% CI, 1.648–13.583; p = 0.004]) were independently associated with sICH. After adjustment of the confounders, patients with sICH had a higher risk of poor outcome (OR, 1.983; 95% CI, 1.117–3.521; p = 0.018) at 3 months and that of all-cause mortality at 3 (OR, 6.135; 95% CI, 2.328–16.169; p < 0.001) and 12 months (OR, 3.720; 95% CI, 1.513–9.148; p = 0.004).Conclusion: sICH occurred in 0.73% of acute ischemic stroke patients without thrombolysis and was associated with a worse prognosis at 3 and 12 months. Atrial fibrillation, history of tumors, and NIHSS score at admission were independent risk factors of sICH.

With over 2 million new cases annually, stroke is associated with the highest disability-adjusted life-years lost of any disease in China. The burden is expected to increase further as a result of population ageing, an ongoing high prevalence of risk factors (eg, hypertension), and inadequate management. Despite improved access to overall health services, the availability of specialist stroke care is variable across the country, and especially uneven in rural areas. In-hospital outcomes have improved because of a greater availability of reperfusion therapies and supportive care, but adherence to secondary prevention strategies and long-term care are inadequate. Thrombolysis and stroke units are accepted as standards of care across the world, including in China, but bleeding-risk concerns and organisational challenges hamper widespread adoption of this care in China. Despite little supporting evidence, Chinese herbal products and neuroprotective drugs are widely used, and the increased availability of neuroimaging techniques also results in overdiagnosis and overtreatment of so-called silent stroke. Future efforts should focus on providing more balanced availability of specialised stroke services across the country, enhancing evidence-based practice, and encouraging greater translational research to improve outcome of patients with stroke.

Cerebral cavernous malformations (CCMs) are one of the most common types of vascular malformation, which are featured enlarged and irregular small blood vessels. The cavernous cavities are merely composed of a single layer of endothelial cells and lack other support tissues, such as elastic fibers and smooth muscle, which make them elastic. CCMs may develop in sporadic or familial forms with autosomal dominant inheritance. Mutations have been identified in three genes: KRIT1, MGC4607, and PDCD10. Here, we report a typical case of CCMs in a 44-year-old woman associated with a novel mutation in PDCD10 gene. The patient, diagnosed with CCMs, has been suffering from headache for several months. Analyses of the Whole Exome Sequencing revealed a novel disease-associated mutation in the already known disease-associated PDCD10 gene. This mutation consists a nucleotide deletion (c.212delG) within the exon 4, resulting in premature protein termination (p.S71Tfs*18). This novel mutation significantly enriches the spectrum of mutations responsible for CCMs, providing a new evidence for further clarifying the genotype-phenotype correlations in CCMs patients.

We report the case of a patient with chronic type A aortic dissection (AD), who had been admitted, 18 months ago, to another hospital with acute chest-tearing pain accompanied with transient loss of consciousness. His symptoms resolved but he reported after discharge a toothache and fluctuating right mandibular pain. He presented to our outpatient clinic because his facial pain aggravated. Physical examination demonstrated a bruit over the right carotid artery. Transthoracic echocardiography and carotid sonography demonstrated aortic dissection extending into the extracranial right internal carotid artery (ICA), which was tortuous. The patient refused surgery. This case reminds us that AD can involve the extracranial ICA, and that long-term survival is possible with type A acute AD without treatment. Carotid ultrasonography is noninvasive, inexpensive, easily performed, and can lead to the detection of chronic type A AD extending to the extracranial ICA.

Objective: This study evaluated iron overload after intracerebral hemorrhage (ICH) using ESWAN sequences.Methods: This single-center prospective observational cohort study enrolled supratentorial ICH patients. MRI was obtained with a 3.0-T scanner at day 1, day 14, day 30, and follow-up (300 days or later). R2* mapping was generated based on the ESWAN. R2* value of the ipsilateral side represented iron deposition, and the R2* value of the contralateral side served as control. R2* value was adjusted by volume and used to assess total iron overload. Brain edema was measured on T2 FLAIR-weighted images. Brain atrophy was calculated as the contralateral hemisphere volume minus the injured hemisphere volume.Results: Twnety-seven patients with a spontaneous supratentorial ICH were included in this analysis. The ipsilateral R2* value was 40.27 ± 11.62, 41.92 ± 13.56, and 60.89 ± 14.09 at days 1, 14, and 30, respectively. The R2* value was significantly higher in the ICH side than the contralateral side (p < 0.01). Increased R2* value was seen on day 30 compared to day 14 (p < 0.01). The R2* value showed logistic decay with the distance to the hematoma margin (p < 0.01). Brain edema at day 14 and brain atrophy at follow-up correlated with R2* value adjusted by volume at day 14 (p < 0.01).Conclusions: After ICH, the iron deposition in the perihematomal region was progressively increased during the first month. R2* value adjusted by volume predicted acute brain edema and chronic brain atrophy.

OBJECTIVE We investigated the characteristics and relationship of co-existing intracranial artery stenosis (ICAS) and extracranial carotid atherosclerosis in an asymptomatic rural population in northern China. METHODS Asymptomatic residents ≥ 30 years old in 13 villages underwent simultaneous cervical vascular and transcranial Doppler ultrasound. ICAS was defined as ≥ 50% stenosis. Extracranial carotid atherosclerosis severity was classified as increased intimal medial thickness (IMT), plaques, and a plaque with ≥ 50% extracranial artery stenosis (ECAS). Demographic details, medical history, and blood biochemistry results were collected. The relationship between ICAS and extracranial carotid atherosclerosis severity was determined using the chi-square trend test and binary logistic regression analysis. RESULTS A total of 2598 asymptomatic participants were included; 122 (4.7%) had ICAS, 1071 (41.2%) had extracranial carotid atherosclerosis, and 84 (3.2%) had co-existing extracranial carotid atherosclerosis and ICAS. Those with co-existing ICAS and extracranial carotid atherosclerosis were older (P = 0.006) and had a higher hypertension (HTN) and diabetes mellitus (DM) prevalence (P

Background: Sphingolipids mainly consist of ceramides (Cer), sphingomyelins (SM) and glycosphingolipids. Sphingolipids are related with coronary heart disease and metabolic disease, but there’re few studies about cerebrovascular disease. The purpose was to detect sphingolipids in plasma of patients with large artery atherosclerosis (LAA) cerebrovascular disease and cerebral small vessel disease (CSVD) to explore the similarities and differences of pathogenesis of the two subtypes. Methods: 20 patients with LAA cerebrovascular disease, 20 patients with age-related CSVD, 10 patients with Fabry disease and 14 controls were enrolled from October 2017 to January 2019. Ultra-high performance liquid chromatography-quadruple-time-of-flight mass spectrometry/mass spectrometry was used to determine sphingolipids. Univariate combined with multivariate analysis was used for comparison. Receiver operating characteristic curves were used to determine sensitivities and specificities. Results: 276 sphingolipids were detected, including 39 Cer, 3 ceramide phosphates, 72 glycosphingolipids and 162 SM. (1) Cer (d36:3), Cer (d34:2), Cer (d38:6), Cer (d36:4) and Cer (d16:0/18:1) were increased in LAA; SM (d34:1), Cer (d34:2), Cer (d36:4), Cer (d16:0/18:1), Cer (d38:6), Cer (d36:3) and Cer (d32:0) were increased in age-related CSVD. (2) Cer (d36:4) and SM (d34:1) were increased in age-related CSVD compared with LAA. (3) Total trihexosyl ceramides were increased in Fabry group compared with control (P Conclusions: Ceramides are increased in both LAA and age-related CSVD, which may be related to similar risk factors and pathophysiological process of arteriosclerosis; SM is increased in both age-related CSVD and Fabry disease, suggesting that increased SM may be associated with CSVD. Glycosphingolipids, trihexosylceramides in particular, are increased in Fabry disease.

Background: Dural arteriovenous fistula (DAVF), characterized by abnormally direct connections between meningeal arteries and meningeal veins or dural venous sinuses, is a rare subtype among the intracranial arteriovenous malformations. Although the clinical manifestations of DAVF are very variable depending on the locations and size of venous drainage, parkinsonism and urinary incontinence are rarely reported. Here, we present a rare case with parkinsonism and urinary incontinence secondary to DAVF. Case presentation: A 50-year-old man was admitted for a progressively worsening weakness of his left lower limb over a year with urinary incontinence for four months. Neurological examination revealed rigidity and bradykinesia of the left upper limb without an obvious tremor. Magnetic resonance imaging exhibited diffuse white matter hyperintensities in bilateral centrum semiovale. Cranial magnetic resonance venography revealed extensive tortuous venous malformations. Digital subtraction angiography exhibited multiple bilaterally distributed DAVF in the superior sagittal sinus, supplied by bilateral occipital arteries and superficial temporal arteries. In the one year follow-up, the patient with multiple DAVF bilaterally distributed was completely cured after endovascular treatment according to the symptoms and the follow-up imaging results. Conclusion: this report enriches the clinical presentations of DAVF with parkinsonism and urinary incontinence, which is a crucial diagnostic clue to be aware of the possibility. Moreover, these rare symptoms can be relieved by timely endovascular treatment.

Background Ischemic stroke is a leading cause of morbidity and mortality. Thrombolytic therapy improves disability and survival rates; however, to be effective, it must be given within 4.5 h of onset. Moreover, thrombolytic therapy is frequently contraindicated. Therefore, alternative therapeutic options are required. In China, cinepazide maleate injection has been shown to improve the cerebral collateral circulation and further reduce disability in stroke patients; however, very few studies investigating this therapy have been conducted to date. Therefore, this study aimed to further confirm the efficacy and safety of cinepazide maleate injection in patients with acute ischemic stroke. Methods Patients with acute ischemic stroke were administered an intravenous infusion of 320 mg cinepazide maleate or placebo once daily for 14 days. All patients were also administered basic therapy (citicoline sodium). The primary efficacy endpoint was the proportion of patients with a modified Rankin scale (mRS) ≤2 on day 90. Secondary efficacy endpoints included Barthel Index ≥95. Safety was evaluated by recording all adverse events (AEs), monitoring laboratory parameters and vital signs, and electrocardiogram. Results In total, 937 patients with an acute ischemic stroke were included, with a mean (standard deviation, SD) National Institutes of Health Stroke Scale score of 8.8 (2.4) and a mean (SD) stroke onset of 30.9 (11.4) hours prior. Following treatment for 90 days, the proportion of patients with an mRS score ≤ 2 was significantly higher in the cinepazide maleate group than in the control group (60.9% vs. 50.1%; p = 0.0004). Moreover, the proportion of patients with a Barthel Index of ≥95 on day 90 was also significantly higher in the cinepazide maleate group than in the control group (53.4% vs. 46.7%; p = 0.0230). There were no statistically significant differences in safety parameters between the cinepazide maleate and control groups. Conclusions The results of this study show that cinepazide maleate injection is superior to placebo in improving neurological function and activities of daily living, reducing disability, and promoting functional recovery in patients with acute ischemic stroke. Cinepazide maleate injection was safe and well tolerated with no unexpected AEs reported. Trial registration Chinese Clinical Trial Registry CTR20160292 and ChiCTR1900023827. Retrospectively registered June 13, 2019.

Background Hereditary spastic paraplegia is a heterogeneous group of clinically and genetically neurodegenerative diseases characterized by progressive gait disorder. Hereditary spastic paraplegia can be inherited in various ways, and all modes of inheritance are associated with multiple genes or loci. At present, more than 76 disease-causing loci have been identified in hereditary spastic paraplegia patients. Here, we report a novel mutation in SPAST gene associated with hereditary spastic paraplegia in a Chinese family, further enriching the hereditary spastic paraplegia spectrum. Methods Whole genomic DNA was extracted from peripheral blood of the 15 subjects from a Chinese family using DNA Isolation Kit. The Whole Exome Sequencing of the proband was analyzed and the result was identified in the rest individuals. RaptorX prediction tool and Protein Variation Effect Analyzer were used to predict the effects of the mutation on protein tertiary structure and function. Results Spastic paraplegia has been inherited across at least four generations in this family, during which only four HSP patients were alive. The results obtained by analyzing the Whole Exome Sequencing of the proband exhibited a novel disease-associated in-frame deletion in the SPAST gene, and this mutation also existed in the rest three HSP patients in this family. This in-frame deletion consists of three nucleotides deletion (c.1710_1712delGAA) within the exon 16, resulting in lysine deficiency at the position 570 of the protein (p.K570del). This novel mutation was also predicted to result in the synthesis of misfolded SPAST protein and have the deleterious effect on the function of SPAST protein. Conclusion In this case, we reported a novel mutation in the known SPAST gene that segregated with HSP disease, which can be inherited in each generation. Simultaneously, this novel discovery significantly enriches the mutation spectrum, which provides an opportunity for further investigation of genetic pathogenesis of HSP.

Tissue reperfusion is a serious therapeutic strategy of ischemic stroke in addition to recanalization. In this work, we aimed to establish new urokinase-based therapeutics in order to dissolve large vessel thrombus together with microthrombi for stroke implications. Formulations consisted of free urokinase (UK), polyethylene glycol–crosslinked urokinase nanogel (PEG-UK), and a 1:1 mixture of UK and PEG-UK (PEG-UK+UK) were tested both in vitro and in vivo. In vitro experiments confirmed the pH-dependent release of PEG-UK in the PEG-UK+UK formulation. It was activated at pH 6.50, an environmental pH in the infarct brain tissue, owing to the dynamic crosslink property of PEG-UK. In vivo tests on a thromboembolic stroke rat model showed that the formulations containing UK, i.e., free UK and PEG-UK+UK, demonstrated better neurological scores and smaller infarction volumes within the time window, in which the PEG-UK+UK formulation relatively performed better. On the other hand, the formulations containing PEG-UK, i.e., PEG-UK and PEG-UK+UK, gained sufficient thrombolytic efficiency beyond the time window. Further investigation on the mechanism revealed that PEG-UK could reduce microthrombus in distal microcirculation, and its destructive effect was also less than that of free UK. The PEG-UK+UK formulation actually provided a “dual targeting” delivery of UK to both the large vessels and the microcirculation, which was beneficial to the treatment of cerebral ischemic stroke both within and beyond the therapeutic time window.

Purpose: We aimed to investigate the prevalence and clinical relevance of the parent artery plaque in acute lacunar stroke. Methods: This prospective, multi-center, observational study included patients with first-ever ischemic stroke within 72 hours of symptom onset. Patients were evaluated by three-dimensional T1-weighted high-resolution magnetic resonance imaging (HR-MRI) and conventional MRI sequences. We examined the presence of intracranial plaque, infarction patterns, and infarct volumes in all the patients with acute lacunar stroke. The outcome measurement was 90-day poor functional outcome (modified Rankin Scale >2). Results: Of the 756 patients included, 341(45.1%) patients had an acute lacunar stroke. There were 201 (58.9%, 201/341) patients with an infarct in deep basal ganglia area. Among them, 64 (31.8%, 64/201) patients had middle cerebral artery (MCA) plaques identified on HR-MRI. The patients with MCA plaque had a similar infarct volume ( 0.93ml vs. 0.88ml , p =0.9) with those without MCA plaque. However, they more likely had an infarct involving posterior limb of internal capsule (42.2%, 27/64 vs. 25.5%, 35/137, p =0.017 ) and had a higher prevalence of cerebral microbleed (68.8%, 44/64 vs. 40.1%, 55/137, p p =0.002) . After adjusting for age and National Institute of Health Stroke Scale (NIHSS) at admission, the presence of MCA plaque was independently associated with 90-day poor functional outcome (OR:3.44, [95% CI,1.26-9.42]). There were 102 (29.9%, 102/341) patients with an infarct in pons. Among them, 66 (64.7%, 66/102) patients had basilar artery (BA) plaques. Patients with BA plaque had a higher prevalence of moderate to severe BG-PVS (42.4%, 28/66 vs. 22.2%, 8/36, p =0.041). There were no differences between the patients with and without BA plaque regarding infarction volume and 90-day functional outcome. Conclusions: Parent artery plaque is common in patients with acute lacunar stroke. We propose the deep basal ganglia area infarct with MCA plaque as a unique lacunar stroke subtype with poor prognosis. Our data did not show the presence of BA plaque have an effect on the lacunar stroke prognosis.

Objective We aimed to evaluate the value of 3D pseudocontinuous arterial spin-labeling (pCASL) perfusion imaging detected crossed cerebellar diaschisis (CCD) at different stages of intracerebral hemorrhage (ICH). Materials and methods We assessed bilateral cerebral blood flow (CBF) values of different brain regions and the relationships between the CCD and clinical status of 16 ICH patients. Results The ICH patients had significantly lower CBF values in the contralateral cerebellum in acute, subacute and chronic stages. The subacute CCD had a significant correlation with clinical status. Conclusions 3D pCASL may be an ideal tool to study the phenomenon and clinical consequences of ICH with CCD.

Objective:To examine whether a change in serum total homocysteine (tHcy) levels is associated with first stroke risk in a post hoc analysis of the China Stroke Primary Prevention Trial (CSPPT).Methods:We analyzed 16,867 participants of the CSPPT with tHcy measurements at both baseline and exit visits. The primary outcome was first stroke. The secondary outcome was a composite of cardiovascular events consisting of cardiovascular death, myocardial infarction, and stroke. The percent decline in tHcy was calculated as [(baseline tHcy − exit tHcy)/baseline tHcy × 100].Results:Over the median treatment duration of 4.5 years, participants who developed a first stroke had a significantly lower percent decline in tHcy (β = −5.7; 95% confidence interval [CI] −8.8 to −2.6) compared to their counterparts. A 20% tHcy decline was associated with a reduction in stroke risk of 7% (hazard ratio [HR] 0.93; 95% CI 0.90–0.97). When percent decline in tHcy was assessed as tertiles, a significantly lower stroke risk was found in those in tertiles 2–3 (HR 0.79; 95% CI 0.64–0.97) compared with participants in tertile 1. Similar results were observed for the composite of cardiovascular events. The beneficial effect associated with greater tHcy reduction was observed across strata for age, sex, treatment group (with vs without folic acid), MTHFR C677T genotypes, baseline tHcy and serum folate levels, and blood pressure control.Conclusions:Percent lowering in tHcy was significantly associated with a reduction in first stroke risk in Chinese adults with hypertension, and if further confirmed, may serve as a useful indicator for folic acid treatment efficacy on stroke prevention.Clinicaltrials.gov identifier:NCT00794885.

Background The present study aimed to investigate the prevalence and risk factors for extracranial carotid artery stenosis (ECAS) and intracranial carotid artery stenosis (ICAS) simultaneously in asymptomatic Chinese pure rural population. Methods We analyzed 2589 asymptomatic subjects aged over 30 yr. by ultrasonography and transcranial Doppler simultaneously in 13 isolated villages by door-to-door investigation. Both ECAS and ICAS were defined as more than 50% stenosis. Demographics, medical history documentation, and investigation of biochemical results were performed for each subject. Univariate and multivariate logistic regression analyses were employed to assess the risk factors associated with ECAS and ICAS, respectively. Results One hundred twenty-two (4.7%) residents with ICAS and 56 (2.2%) with ECAS were found in 2589 subjects. Three factors emerged as independent risk factors for ICAS: age (95% confidence interval [CI] = 1.01–1.04, odds ratio [OR] = 1.07), hypertension (95% CI = 1.98–4.37, OR = 2.94), and diabetes mellitus (95% CI = 1.72–4.38, OR = 2.75). As for ECAS, five factors presented as independent risk factors: age (95% CI = 1.09–1.11, OR = 1.10), male sex (95% CI = 1.01–1.02, OR = 1.01), diabetes mellitus (95% CI = 1.10–2.12, OR = 1.53), systolic blood pressure (95% CI = 1.95–2.88, OR = 2.37), and total cholesterol (95% CI = 1.00–1.13, OR = 1.06). Conclusions ICAS and ECAS were relatively common among asymptomatic rural Chinese subjects. Although they shared similar risk factors, differences still existed between them.

A novel normal-phase UPLC-QToF MS method was developed for sphingolipids analysis, which was then applied to separate and identify seven classes of sphingolipids in plasma. The time-consuming of this novel method was much shorter than previous 2D LC–MS method, while the sensitivity, repeatability and resolution for sphingolipids analysis were better or comparable. Besides, the differences of lipids in human plasma among diabetes mellitus patients, diabetes mellitus associated with atherosclerosis patients and control subjects were also compared. Finally, 12 sphingolipids species were identified as the amounts of which in diabetes mellitus associated with atherosclerosis patients were significantly higher than them in diabetes mellitus patients (VIP >1.0, p value 1.5). As the isomers of GalCs and GluCs were successfully separated, it was found that five GluCs, rather than GalCs, were included in these 12 potential biomarkers. These results suggest the need to separate GalCs from GluCs, and also indicated that there may be some extra activation pathways of diabetes mellitus associated with atherosclerosis, different from the atherosclerosis pathway and the diabetes mellitus pathway, causing cardiovascular disease.

Rationale Stroke presents a serious health problem in China. Despite progresses made in recent years, there is still a lack of effective treatments for acute ischemic stroke (AIS) in clinical practices. Aims The Chinese Acute Ischemic Stroke Treatment Outcome Registry (CASTOR) is designed to evaluate the patterns and cost-effectiveness of current treatments for AIS in real-world settings in China. Design CASTOR is a prospective, multi-center study registered with ClinicalTrials.gov (NCT02470624) with a target sample size of 10,000 patients who are experiencing AIS. The patients are treated for AIS following the Chinese stroke guideline and local practice. Real-world data on treatment regimens, outcomes and costs are collected at baseline (Visit 1) and during subsequent visits (Visit 2 to Visit 5) after medication treatments. Outcome The primary objective of the present study is to analyze the current treatment status of AIS in real world settings. The secondary objectives include: 1) to compare the effectiveness of common treatment regimens, 2) to analyze the cost-effectiveness of different treatment regimens for AIS, 3) to analyze the incidence of adverse events and complications in enrolled patients with AIS, 4) to analyze the effect of Trial of Org 10,172 in Acute Stroke Treatment (TOAST) classification on the specific therapies during acute phase treatment period. Discussion In face of changing treatment patterns and increasing demand from medical insurers for cost-effectiveness data in China, a large-scale registry study examining the real-world patterns of AIS in hospitals is needed. The CASTOR study will help to find favorable cost-utility treatment regimens for AIS and improve the overall treatment outcome of Chinese patients with AIS. Electronic supplementary material The online version of this article (doi:10.1186/s12906-017-1863-4) contains supplementary material, which is available to authorized users.

Background and Purpose— CD163, a receptor for hemoglobin, is involved in hemoglobin clearance after intracerebral hemorrhage (ICH). In contrast to microglial/macrophage CD163, neuronal CD163 hemoglobin has not been well studied. This study examined the expression of neuronal CD163 in a pig model of ICH and in vitro rat cortical neurons and the impact of deferoxamine on that expression. Methods— There were 2 parts to this study. In the in vivo part, piglets had injection of autologous blood into the right frontal lobe. The time course of CD163 expression and the effect of deferoxamine on the expression of CD163 after ICH were determined in the grey matter. In the in vitro part, the levels of CD163 and neuronal death and the effect of deferoxamine were examined in rat cortical neurons culture treated with hemoglobin. Results— CD163-positive cells were found, and the CD163 protein levels were upregulated in the ipsilateral grey matter after ICH. The CD163 levels peaked at days 1 and 3. The CD163-positive cells were colocated with NeuN-positive, heme oxygenase-2–positive, and terminal deoxynucleatidyl transferase dUTP nick end labeling–positive cells. Deferoxamine treatment attenuated ICH-induced CD163 upregulation and significantly reduced both brain CD163 and hemoglobin levels at day 3. Treating neuronal cultures with hemoglobin for 24 hours resulted in CD163 upregulation and increased cell death. Deferoxamine significantly attenuated the hemoglobin-induced neuronal death and CD163 upregulation. Conclusions— CD163 is expressed in neurons and upregulated after ICH. Deferoxamine reduced ICH-induced CD163 upregulation and brain cell death in vivo and hemoglobin-induced CD163 upregulation and neuronal death in vitro.

The relation between obesity and stroke outcome has been disputed. This study was aimed to determine the association of body mass index (BMI) with mortality and functional outcome in patients with acute ischemic stroke. Data were from a national, multi-centre, prospective, hospital-based register: the ChinaQUEST (Quality Evaluation of Stroke Care and Treatment) study. Of 4782 acute ischemic stroke patients, 282 were underweight (BMI 2), 2306 were normal-weight (BMI 18.5 to 2), 1677 were overweight (BMI 24 to 2) and 517 were obese (BMI ≥ 28 kg/m2). The risks of death at 12 months and death or high dependency at 3 and 12 months in overweight (HR: 0.97, 95% CI: 0.78–1.20; OR: 0.93, 95% CI: 0.80–1.09; OR: 0.95, 95% CI: 0.81–1.12) and obese patients (HR: 1.07, 95% CI: 0.78–1.48; OR: 0.96, 95% CI: 0.75–1.22; OR: 1.06, 95% CI: 0.83–1.35) did not differ from normal-weight patients significantly after adjusting for baseline characteristics. Underweight patients had significantly increased risks of these three outcomes. In ischemic stroke patients, being overweight or obese was not associated with decreased mortality or better functional recovery but being underweight predicted unfavourable outcomes.

Stroke is a major cause of mortality and long-term disability worldwide. The study of biomarkers and pathogenesis is vital for early diagnosis and treatment of stroke. In the present study, a continuous-flow normal-phase/reversed-phase two-dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry (NP/RP 2D LC-QToF/MS) method was employed to measure lipid species in human plasma, including healthy controls and lacunar infarction (LI) patients. As a result, 13 lipid species were demonstrated with significant difference between the two groups, and a "plasma biomarker model" including glucosylceramide (38:2), phosphatidylethanolamine (35:2), free fatty acid (16:1), and triacylglycerol (56:5) was finally established. This model was evaluated as an effective tool in that area under the receiver operating characteristic curve reached 1.000 in the discovery set and 0.947 in the validation set for diagnosing LI patients from healthy controls. Besides, the sensitivity and specificity of disease diagnosis in validation set were 93.3% and 96.6% at the best cutoff value, respectively. This study demonstrates the promising potential of NP/RP 2D LC-QToF/MS-based lipidomics approach in finding bio-markers for disease diagnosis and providing special insights into the metabolism of stroke induced by small vessel disease. Graphical abstract Flow-chart of the plasma biomarker model establishment through biomarker screening and validation.

Introduction: In this study we investigated the relationships between anti-ganglioside antibodies and Guillain–Barre syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP). Methods: Samples from 48 Chinese patients diagnosed with GBS and 18 patients diagnosed with CIDP were retrospectively reviewed. Results: In the GBS patients, 62.5% were classified as having acute inflammatory demyelinating polyneuropathy (AIDP), 27.1% were found to have acute motor axonal neuropathy (AMAN), and 10.4% were unclassified. Serum IgG anti-ganglioside antibodies were detected in 46.2% of the AMAN patients and in 6.7% of the AIDP patients (P < 0.05); 5.6% of the 18 CIDP patients were IgG antibody positive, and 27.8% were IgM antibody positive. Facial palsy and sensory impairment were significantly associated with IgM antibodies. Conclusions: These results suggest that IgG anti-GM1 antibodies are associated with AMAN, but not with AIDP, and that IgM antibodies against GM1, GM2, and GM3 are associated with facial nerve palsy. Muscle Nerve 55: 470–475, 2017

Background and Purpose— We sought to determine whether folic acid supplementation can independently reduce the risk of first stroke associated with elevated total cholesterol levels in a subanalysis using data from the CSPPT (China Stroke Primary Prevention Trial), a double-blind, randomized controlled trial. Methods— A total of 20 702 hypertensive adults without a history of major cardiovascular disease were randomly assigned to a double-blind daily treatment of an enalapril 10-mg and a folic acid 0.8-mg tablet or an enalapril 10-mg tablet alone. The primary outcome was first stroke. Results— The median treatment duration was 4.5 years. For participants not receiving folic acid treatment (enalapril-only group), high total cholesterol (≥200 mg/dL) was an independent predictor of first stroke when compared with low total cholesterol (P =0.001). Folic acid supplementation significantly reduced the risk of first stroke among participants with high total cholesterol (4.0% in the enalapril-only group versus 2.7% in the enalapril–folic acid group; hazard ratio, 0.69; 95% confidence interval, 0.56–0.84; P P =0.982). The effect was greater among participants with elevated total cholesterol ( P for interaction=0.024). Conclusions— Elevated total cholesterol levels may modify the benefits of folic acid therapy on first stroke. Folic acid supplementation reduced the risk of first stroke associated with elevated total cholesterol by 31% among hypertensive adults without a history of major cardiovascular diseases. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00794885.

Endoplasmic reticulum (ER) stress is essential for brain ischemia/reperfusion (I/R) injury. However, whether it contributes to I/R-induced blood-brain barrier (BBB) injury remains unclear. cilostazol exerts protective effects toward I/R-induced BBB injury, with unclear mechanisms. This study explored the potential role of ER stress in I/R-induced endothelial cell damage and determined whether the therapeutic potential of cilostazol, with respect to I/R-induced endothelial cell damage, is related to inhibition of ER stress. We found that exposing brain endothelial cells (bEnd.3) to oxygen-glucose deprivation/reoxygenation (OGD/R) significantly activated ER stress and diminished the barrier function of cell monolayers; treatment with the ER stress inhibitor 4-phenylbutyric acid (4-PBA) or cilostazol prevented OGD/R-induced ER stress and preserved barrier function. Furthermore, OGD/R induced the expression and secretion of matrix metalloproteinase-9 and nuclear translocation of phosphorylated NF-κB. These changes were partially reversed by 4-PBA or cilostazol treatment. In vivo, 4-PBA or cilostazol significantly attenuated I/R-induced ER stress and ameliorated Evans blue leakage and tight junction loss. These results demonstrate that I/R-induced ER stress participates in BBB disruption. Targeting ER stress could be a useful strategy to protect the BBB from ischemic stroke, and cilostazol is a promising therapeutic agent for this process.-Nan, D., Jin, H., Deng, J., Yu, W., Liu, R., Sun, W., Huang, Y. Cilostazol ameliorates ischemia/reperfusion-induced tight junction disruption in brain endothelial cells by inhibiting endoplasmic reticulum stress.

We described a female patient with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis occurring sequentially with neuromyelitis optica spectrum disorders (NMOSD). The 19-year-old patient initially presented a diencephalic syndrome with aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) and brain lesions which involving bilateral medial temporal lobes and periependymal surfaces of the third ventricle on magnetic resonance imaging (MRI). Ten months later, the patient developed cognitive impairment, psychiatric symptoms and dyskinesia with left basal ganglia lesions on brain MRI. Meanwhile, the anti-NMDAR antibodies were positive in the patient's serum and cerebrospinal fluid, while the screening tests for an ovarian teratoma and other tumors were all negative. Hence, the patient was diagnosed NMOSD and anti-NMDAR encephalitis followed by low-dose rituximab treatment with a good response. This case was another evidence for demyelinating syndromes overlapping anti-NMDAR encephalitis in Chinese patients.

Background Although chronic kidney disease has been linked to cerebral small-vessel disease (CSVD), a definite relationship between them has not been established. This study assessed whether low estimated glomerular filtration is associated with risk of different subtypes of CSVDs. Methods Electronic databases were systematically searched for studies reporting an odds ratio of the association between low estimated glomerular filtration and CSVD risk. Sixteen studies, including 10,534 participants, were identified. A fix effects model was applied and odds ratios (ORs) with 95% confidence intervals were presented. Results Overall, risk of CSVDs was greater in individuals with low estimated glomerular filtration (OR = 2.20). Stratified analyses consistently showed significant associations across different subtypes, with pooled OR being greatest in subjects with silent cerebral infarction (SCI) (OR = 2.71) and cerebral microbleed (OR = 2.70). A pooled estimate of studies showing OR as a continuous variable showed results consistent with the former analysis (OR = .98 per standard deviation decrease) in low estimated glomerular filtration. Conclusions This study revealed that low estimated glomerular filtration was significantly associated with risk of CSVDs. Low estimated glomerular filtration was most strongly associated with SCI (OR = 2.71) among subtypes of CSVDs.

pH-sensitive polyethylene glycol-conjugated urokinase nanogels (PEG-UKs) were previously reported to be a new form of UK nanogels that could release UK at certain pH values. In this study, we evaluated the effect of PEG-UK targeted to ischemic tissue with microcirculation failure in rat model of ischemic stroke and investigated the possible mechanisms of action.Surgeries were performed to induce persistent middle cerebral artery (MCA) occlusion in adult Sprague-Dawley rats. The pH distribution in the brain was mapped 1h after ischemia using a needle-type pH micro sensor. The release curve of active UK from PEG-UK was also mapped by a continuous measurement of the peripheral blood. The thrombolytic effects of PEG-UK, when it was administrated 1h after occlusion, including dynamic changes in the D-dimer level, neurological deficits and infarction volume, were observed. Next, the possible mechanisms underlying these effects were explored, including the BBB integrity and the extent of apoptosis and neurotoxicity. Additionally, the long-term effects of PEG-UK during the four weeks after treatment were evaluated using the dynamic changes in the body weights and clinical scores and the numbers of deaths and hemorrhagic transformations (HTs). To evaluate the systemic side effects of PEG-UK, the fluctuations of cytokines in the liver and kidney were evaluated.On average, MCA occlusion for 1h induced an approximately 0.49 decline in the pH value (from 7.12 to 6.73), and the lowest value was 6.32 in the predominantly affected region around the cortex. PEG suspended the release of UK from PEG-UK into the circulation. When it was administrated 1h after occlusion, PEG-UK treatment clearly reduced the severity of neurological deficits in the acute phase (P=0.001). The relative infarct volume also decreased significantly in PEG-UK rats (P0.001). As to the integrity of BBB, the EB leakage in the PEG-UK group was reduced (P=0.001). Maintenance of the expression of TIMP-1 (P=0.032) and claudin5 (P0.001) and inhibition of MMP9 upregulation (P0.001) were observed through both immunohistochemistry and Western blot in the PEG-UK group. Moreover, the expression of both NMDAR1 (P0.001) and Caspase9 (P=0.013) in PEG-UK-treated rats was reduced. As to the long-term prognosis, the rats in PEG-UK group recovered faster and better, and the numbers of deaths and HTs were not increased. No significant fluctuation in IL-1β and TNF-α was found in the PEG-UK-treated rats during the four post-treatment weeks. When PEG-UK was administrated 2.5h after occlusion, no clearly better outcomes were observed; however, the number of HTs was not increased.Treatment with PEG-UK decreased the severity of ischemic stroke by improving ischemic brain tissue and protecting the BBB and by inhibiting apoptosis and decreasing neurotoxicity. PEG-UK could further inhibit HT through its BBB protection effect. The administration of PEG-UK also improved the long-term prognosis and had no obvious systemic side effects in rats. Our data provide new insights into the thrombolytic treatment of ischemic stroke.

The protective effect of high-density lipoprotein (HDL) on endothelial function is impaired in patients with type 2 diabetes mellitus (T2DM), which may result in atherosclerotic complications. Naoxintong (NXT) is a compound preparation that includes Radix Astragali, Angelicae sinensis, Radix Paeoniae Rubra and Ligusticum wallichii. It is widely administered in China to prevent atherosclerotic complications. In the present study, NXT was administered to 69 patients with T2DM. HDLs were isolated from patient blood samples prior to and following the intervention. In vitro endothelial functions of HDL, including proliferation, migration, angiogenesis, and anti-apoptosis were investigated by bromodeoxyuridine, wound healing, Transwell and Matrigel tube formation assays on human umbilical vein endothelial cells (HUVECs). The results from the present study demonstrated that HUVECs treated with HDL isolated from diabetic patients following NXT therapy exhibited increased proliferative effects (10–27%; P

Background Olfactory testing is a useful tool in the differential diagnosis of Parkinson's Disease (PD). Although fast and easy to use, the high intercultural variability of odor detection limits the world-wide use of the most common test sets. Objective The aim of this study was to test one of the most commonly used olfactory tests (Sniffin' Sticks 12-identification test) in an adapted version for a Chinese population of healthy subjects and PD patients. Methods For this purpose, cohorts of 39 Chinese and 41 German PD patients as well as 70 Chinese and 100 German healthy subjects have been examined both with the original and the adapted version of the Sniffin' Sticks test, the latter being designed according to the regional culture. Results The adapted Chinese version of the Sniffin' Sticks 12 identification test proved to discriminate Chinese PD patients from controls with a high specificity but relatively low sensitivity. Yet not all odor exchanges would have been necessary as the original odors including liquorice and coffee showed an equally high identification rate in the Chinese and German cohorts. Conclusions The results showed that the newly adapted test could be used as a screening test for PD related olfactory dysfunction in a Chinese population. However further investigation will be necessary to optimize the selection of odors for the Chinese version of the test.

Early hemolysis occurs in the hematoma within 24 h in rat model of intracerebral hemorrhage (ICH). The present study investigated the prevalence of early hemolysis in ICH patients using MRI and the relationship between early hemolysis and perihematomal edema. Thirty ICH patients were prospectively enrolled within 24 h of onset. All patients had cranial CT on admission. Cranial MRI with T2 FLAIR-weighted imaging and T2*-weighted imaging were undertaken at days 1 and 14. The evolution of a non-hypointense lesion on T2*-weighted images and the relationship between the volume of that non-hypointense lesion and perihematomal edema volume were investigated. MRI images of 15 patients were analyzed. The median hematoma volume was 16.3 ml on admission. All patients underwent a baseline MRI within 24 h of ICH onset and showed a non-hypointense lesion within the hematoma on T2*-weighted images. The volume of non-hypointense lesion on T2*-weighted image was 6.0 (8.9) ml at day 1 and 8.6 (17.3) ml at day 14. The absolute perihematomal edema volume was 16.0 (17.9) ml and 24.8 (27.5) ml at days 1 and 14, respectively. There was a linear correlation between non-hypointense T2* lesion and perihematomal edema volume at day 1 and day 14 (p

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small artery disease caused by NOTCH3 gene mutation. Here we report clinical, pathological and genetic profiles of 29 newly-diagnosed CADASIL patients, evaluation of the CADASIL scale in Chinese CADASIL patients, and reanalysis of all reported mainland Chinese patients with identified NOTCH3 gene mutation. We found two novel mutations (p.C134G and p.C291Y) and 13 reported NOTCH3 mutations in the newly-diagnosed group. CADASIL scale score was less than the cutoff score in 19 of 53 Chinese patients with NOTCH3 mutation, generating only a sensitivity of 64.1%. At the time of study, the total number of genetically confirmed CADASIL cases reached 158 from 97 unrelated mainland Chinese families, with 9/97 (9.3%) sporadic patients. The NOTCH3 gene mutation profile showed 43 mutations, with hotspots in exon 4, followed by exon 3. The considerable variability in onset age and CADASIL scale score in patients carrying the same NOTCH3 missense mutation suggested no obvious phenotype–genotype correlation. In conclusion, we report two novel mutations which expand the NOTCH3 mutational spectrum. Exons 4 and 3 are hotspots in mainland Chinese patients with NOTCH3 mutation. The low sensitivity of CADASIL scale in our patients group indicated that the CADASIL scale should be refined according to the clinical characteristics of Chinese CADASIL patients when used in Chinese populations.

Background Several simple clinical grading scores have been developed for intracerebral hemorrhage, primarily to predict 30-day mortality. Aims We aimed to determine the accuracy of three popular scores (original intracerebral hemorrhage, modified intracerebral hemorrhage, and intracerebral hemorrhage grading scale) on 30-day mortality and 90-day death or major disability, and whether the magnitude of benefit varies according to prognosis graded by the three predictive scores. Methods Data from the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial which included 2839 intracerebral hemorrhage patients (Results Among 2556 (90%) participants with available data, the modified intracerebral hemorrhage had the highest discrimination (receiver operator characteristic 0·75) for 90-day poor outcome compared with the original intracerebral hemorrhage (receiver operator characteristic 0·68) and intracerebral hemorrhage grading scale (receiver operator characteristic 0·69). All scores had good positive predictive value (approximately 80–90%) for poor outcome but poor sensitivity and positive predictive value for death. The scores do not clearly discriminate a patient group most likely to benefit from blood pressure lowering. Conclusions Intracerebral hemorrhage prognostic scores are not useful in defining patients at high probability of early death, but they are reliable for predicting poor outcome, defined by death or major disability. Potential benefits of early intensive blood pressure lowering are broadly applicable across grades of severity defined by such scores.

Background and Purpose— We developed and validated a simple algorithm to predict the risk of hematoma growth in acute spontaneous intracerebral hemorrhage (ICH) to better inform clinicians and researchers in their efforts to improve outcomes for patients. Methods— We analyzed data from the computed tomography substudies of the pilot and main phases of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials (INTERACT1 and 2, respectively). The study group was divided into a derivation cohort (INTERACT2, n=964) and a validation cohort (INTERACT1, n=346). Multivariable logistic regression was used to identify factors associated with clinically significant (≥6 mL) increase in hematoma volume at 24 hours after symptom onset. A parsimonious risk score was developed on the basis of regression coefficients derived from the logistic model. Results— A 24-point BRAIN score was derived from INTERACT2 (C-statistic, 0.73) based on baseline ICH volume (mL per score, ≤10=0, 10–20=5, >20=7), recurrent ICH (yes=4), anticoagulation with warfarin at symptom onset (yes=6), intraventricular extension (yes=2), and number of hours to baseline computed tomography from symptom onset (≤1=5, 1–2=4, 2–3=3, 3–4=2, 4–5=1, >5=0) predicted the probability of ICH growth (ranging from 3.4% for 0 point to 85.8% for 24 points) with good discrimination (C-statistic, 0.73) and calibration (Hosmer–Lemeshow P =0.82) in INTERACT1. Conclusions— The simple BRAIN score predicts the probability of hematoma growth in ICH. This could be used to improve risk stratification for research and clinical practice. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00226096 and NCT00716079.

The relationship between blood pressure(BP) and clinical outcome in patients with acute stroke is still controversial. The present study aimed to elucidate the impact of admission blood pressure on mortality in patients with acute stroke of different subtypes. Data were from ChinaQUEST (QUality Evaluation of Stroke Care and Treatment), a multicenter, prospective hospital registry study in 37 cities across China. A total of 6427 patients were admitted within 24 h of onset and after following up for 12 months, 5501 were included in the final analysis. Multivariate Cox regression model were used in data analysis. A “U-curve shaped” relationship was observed between admission systolic or diastolic BP and mortality at 12 months in the overall study population. Compared to first quartile, the Hazard ratio (HR) for the systolic BP of top quartile was 1.444 (95%CI 1.854–1.636), while the HR was 0.692 (95%CI 0.802–0.930) for the second quartile. Similar associations were observed when we applied admission diastolic BP. In subgroup analysis, the U-shaped effect was remained only in patients with intracranial hemorrhage (ICH). The HR for the systolic BP of top quartile was 2.274 (95%CI 1.878–2.755), while the HR was 0.751 (95%CI 0.571–0.986) for the second quartile. Moreover, admission diastolic BP of top quartile was significantly associated with elevated risk of death for patients with ischemic stroke caused by small vessel diseases (LACI)(HR 1.470; CI 1.040–2.078). In addition, we found a heterogeneity of the admission BP distribution among different subtypes, which may explain the “U-curve” effect.

Background The optimal range of blood pressure variability remains unclear. We aimed to stratify the degree of risk of stroke based on visit‐to‐visit systolic blood pressure (SBP) variability in a large Chinese hypertensive population in 32 communities. Methods and Results We retrospectively analyzed the data of 20 702 hypertensive patients from the China Stroke Primary Prevention Trial. The participants were randomized into 2 treatment groups to receive either enalapril or enalapril plus folic acid. Their blood pressures were measured every 3 months. The outcome was the first stroke. Three parameters of SBP variability were calculated: standard deviation, coefficient of variation, and average real variability. The records of first 4, 6, 8, 10 and 12 visits at which SBP was measured were used to calculate SBP variability and to predict subsequent stroke risk in adjusted Cox regression models. After median follow‐up of 4.5 years, 597 patients had experienced stroke. Visit‐to‐visit SBP variability was an independent predictor of subsequent stroke (eg, the hazard ratio for the highest quintile of average real variability [22.67–61.07 mm Hg] over 6 visits was 1.55, 95% CI 1.07–2.25, P =0.021), independent of mean SBP over the follow‐up period. Its value was more predictive when more blood pressure records were used. Conclusions Visit‐to‐visit SBP variability is an independent predictor of primary stroke in Chinese hypertensive patients. This predictive value depends on the number of blood pressure measurements used to calculate variability but is independent of mean SBP. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00794885.

Introdution: Intracranial artery atherosclerosis is an important cause of ischemic stroke, especially in people of Asian origin. Intraplaque hemorrhage is supposed to be a predictor of ischemic event. The goal of this study was to examine the occurrence of intraplaque hemorrhage in a large cohort of Chinese patients with acute ischemic stroke. Methods: Patients with first ever stroke within 72 hours from onset, confirmed by diffusion weighted imaging, were recruited from 16 medical centers. Conventional MRI, magnetic resonance angiography, HRMRI (including 3-dimentional T1 images and 2-dimentional T2 images), and SWI were performed. Intraplaque hemorrhage was identified if hyperintense signals on 3-dimentional T1 images of HRMRI were observed within intracranial plaques. Results: Six hundred and one patients (70% male, mean age 61±16 years old, mean NIHSS 6± 5) were enrolled. Median time from symptom onset to MRI was 44 ± 20 hours. Of them, 240(40%) were diagnosed with large artery atherosclerosis (LAA) stroke. Intracranial intraplaque hemorrhage was identified in 15 intracranial plaques of 13 patients with LAA stroke. Six plaques with intraplaque hemorrhage were asymptomatic and irrelevant to ischemic infarct lesions. In 2 patients, both symptomatic and asymptomatic intraplaque hemorrhage were observed. Conclusions: The prevalence of intracranial intraplaque hemorrhage was low (5.4%)in acute stroke patients. The clinical importance of asymptomatic intraplaque hemorrhage need further investigations.

Background: Pathology studies suggested obstruction of the origins of penetrating arteries by parent intracranial artery plaque can cause an infarct. Using high-resolution magnetic resonance imaging(HRMRI), intracranial plaque distribution can be identified in vivo. We aimed to investigate the occurrence rate of parent intracranial artery plaque in patients with acute penetrating artery territory infarcts. Methods: Patients with first ever stroke within 72 hours from onset, confirmed by diffusion weighted imaging, were recruited from 16 medical centers. Conventional magnetic resonance imaging (MRI), magnetic resonance angiography, HRMRI (including 3-dimentional T1 images and 2-dimentional T2 images) and susceptibility-weighted imaging were performed. All patients received thorough evaluations to determine the cause of stroke according to TOAST classifications. A plaque was identified if there was eccentric wall thickening, whereas the thinnest part was estimated to be less than 50% of the thickest point by visual inspection. The plaques within middle cerebral artery(MCA) were further classified based on their orientation being centered on the superior, inferior, dorsal, or ventral side of the vessel. Possible culprit plaques were defined if superior and/or dorsal MCA plaques ipsilateral to the infarcts were observed. The plaques within basilar artery were further classified based on their orientation being centered on the ventral, dorsal, or lateral sides of the vessel ( ipsilateral to infarcts, or contralateral to infarcts). Possible culprit plaques were defined if dorsal plaques or the plaques ipsilateral to brain stem infarcts were observed. Results: Six hundred and one patients (70% male, mean age 61±16 years old, mean NIHSS 6± 5) were enrolled. Two hundred and eighty-eight(48%) patients were diagnosed with penetrating artery territory infarcts. Of them, 139 patients(48%, 85 MCAs and 54 BAs) had a plaque within the parent intracranial artery of the infarcts. Most of the parent artery plaques(119,85%) were identified as possible culprit plaques. Conclusions: High occurrence rate of parent intracranial artery plaques was observed in patients with acute penetrating artery territory infarcts.

Background: The presence of luminal thrombus is associated with a high risk of stroke recurrence. Using high-resolution magnetic resonance imaging(HRMRI) and susceptibility-weighted imaging(SWI), luminal thrombus can be identified in vivo. We aimed to investigate the occurrence of luminal thrombus in patients with acute ischemic stroke. Methods: Patients with first ever stroke within 72 hours from onset, confirmed by diffusion weighted imaging, were recruited from 16 medical centers. Conventional MRI, magnetic resonance angiography, HRMRI (including 3-dimentional T1 images and 2-dimentional T2 images), and SWI were performed. Luminal thrombus was identified if isointense/hyperintense signals on 3-dimentional T1 images of HRMRI or susceptibility vessel sign on SWI were observed within the course of intracranial arteries. Results: Six hundred and one patients (70% male, mean age 61±16 years old, mean NIHSS 6± 5) were enrolled. Among them, 112 patients underwent recanalization therapies. Median time from symptom onset to MRI was 44 ± 20 hours. Luminal thrombus was identified in 138 (23%)patients. The occurrence rate of luminal thrombus was non-significantly different between the patients treated with and without recanalization therapies(16% vs.25%, p=0.054). Symptomatic luminal thrombus was more likely observed in large artery atherosclerosis stroke(121/240,50%) and cardicac stroke(11/36,31%) than other stroke subtypes (0/288 in lacunar stroke, 0/6 in stroke of undetermined etiology and 1/31 in cryptogenic stroke, P Conclusions: Luminal thrombus is common in patients with acute ischemic stroke within 72 hours from onset. Further studies are required to clarify whether in vivo thrombus imaging can predict early stroke recurrence.

Rationale: Detection of aquaporin-4 (AQP4) antibody in cerebrospinal fluid (CSF) was not suggested for the diagnosis of neuromyelitis opica spectrum disorders (NMOSD). However, some patients with NMOSD have only AQP4 antibody positive in CSF but not in serum with unknown cause. Besides, it is rarely reported that NMOSD complicated with renal clear cell carcinoma. So, the relationship between AQP4-Ab, NMOSD and malignant tumors warrants an investigation. Patients concerns: A 31-year-old female presented in our hospital with chief complaints of urinary retention and weakness in bilateral lower extremities for more than 10 days. Diagnoses: The patient was diagnosed as NMOSD by neuroimaging and laboratory examination, with AQP4 antibody positive only in CSF. Besides, asymptomatic clear cell carcinoma was also found in left kidney. Interventions: The patient underwent 2-month immunosuppressive therapy for NMOSD at first, including intravenous administration of immunoglobulin (IVIG) and methylprednisone, with oral drugs of predisone and tacrolimus. After that, Partial nephrectomy of left kidney was performed. Outcomes: The patient demonstrated almost complete remission for NMOSD after immunosuppressive therapy, and the renal tumor was cured by partial nephrectomy. Lesson: This case indicates that neuromyelitis optica (NMO)-IgG positive only in CSF could have potential association with the etiology of NMOSD, and renal clear cell carcinoma could be found complicated with NMOSD coincidently. Besides, it is necessary to examine NMO-IgG in CSF for patients suspicious with NMOSD, even when the serum test is negative, especially for those with complicated malignant tumors.