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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: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 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.

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.

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.

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.

Background and Purpose— Cerebral microbleeds (CMB) and white matter lesions (WML) are cerebral small vessel diseases. Hypertension is considered the most important risk factor. Its mechanism is not yet clarified. Our study assessed the association of blood pressure variability (BPV) with CMB and WML progression. Methods— Patients with a history of ischemic stroke within 1 to 6 months were consecutively recruited and followed-up for 12 to 18 months. Blood pressure was measured monthly and controlled to a target level. BPV was quantified by the maximum, standard deviation, coefficient of variation, successive variation, standard deviation independent of mean, and successive variation independent of mean. Magnetic resonance imaging was performed at baseline and the end of the study. CMB and WML were rated using Microbleed Anatomic Rating Scale and Age-Related White Matter Changes scales, respectively. Multiple logistic analyses assessed BPV associations with CMB and WML development. Results— Of 720 patients recruited, 500 and 584 had follow-up results for CMB and WML, respectively; 13.2% and 48.1% showed CMB and WML progression, respectively, over a median of 14 months. Patients with CMB had a higher mean, maximum, standard deviation, coefficient of variation, successive variation, standard deviation independent of the mean, and successive variation independent of the mean in either systolic blood pressure or diastolic blood pressure ( P Conclusion— BPV independently predicts CMB progression in deep and infratentorial regions. Clinical Trial Registration Information— URL: http://www.clinicaltrials.gov . Unique identi-fier: NCT00202020.

Objective: Uncertainty exists over the size of potential beneficial effects of medical treatments targeting hematoma growth in intracerebral hemorrhage (ICH). We report associations of hematoma growth parameters on clinical outcomes in the pilot phase, Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT1) (ClinicalTrials.gov NCT00226096). Methods: In randomized patients with both baseline and 24-hour brain CT (n = 335), associations between measures of absolute and relative hematoma growth and 90-day poor outcomes of death and dependency (modified Rankin Scale score 3–5) were assessed in logistic regression models, with data reported as odds ratios (OR) and 95% confidence intervals (CI). Results: A total of 10.7 mL (1 SD) increase in hematoma volume over 24 hours was strongly associated with poor outcome (adjusted OR 1.72, 95% CI 1.19–2.49; p = 0.004). An association was also evident for relative growth (adjusted OR 1.67, 95% 1.22–2.27; p = 0.001 for 1 SD increase). The analyses were adjusted for age, sex, achieved systolic blood pressure, elevated NIH Stroke Scale score (≥14), hematoma location, baseline hematoma volume, intraventricular extension, antithrombotic therapy, baseline glucose, time from ICH to baseline CT scan, and time from baseline to repeat CT scan. A 1 mL increase in hematoma growth was associated with a 5% (95% CI 2%–9%) higher risk of death or dependency. Conclusion: Medical treatments, such as rapid intensive blood pressure lowering, could achieve ∼2–4 mL absolute attenuation of hematoma growth. There is hope that this could translate into modest but still clinically worthwhile (∼10%–20% better chance) outcome from ICH.

Background: pH sensitive polyethylene glycol-urokinase nanogels(PEG-UK) was reported previously as a new form of UK, which could release UK at certain pH value and has the same thrombolytic effect as naked UK on human clots in vitro. In this study, we evaluated its effect in rat model of ischemic stroke and further investigated possible mechanisms. Methods: Persistent middle cerebral artery occlusion were induced in adult Sprague-Dawley rats. pH distribution in the brain was mapped at 1 hour after ischemia through Needle type pH micro sensor and pH Optica Micro system. Thrombolytic effect of PEG-UK, such as dynamic levels of D-dimer, neurological deficts and infarction volume, were examined respectively. In spite of the overall performances, possible mechanisms were also explored, for example, the permeability of blood-brain barrier(BBB) reflected by Evans Blue(EB) leakage, BBB’s integrity via matrix metalloproteinase 9 (MMP9), tissue inhibitor of metalloproteinase protein-1 (TIMP-1) and Claudin5, and extent of apoptosis and neurotoxicity standed by Caspase9 and N-methyl-D-aspartic acid receptor 1(NMDAR1). Results: In ischemic hemisphere, pH value near cortex was obviously lower than that in deeper white matter. Averagely, occlusion for 1 hour induced the decline of pH value for about 0.49, and the lowest value reached to 6.32. Treatment with PEG-UK brought obvious alleviation of neurological deficts in acute phase( P =0.001). A significant reduction of relative infarction volume was also proved in PEG-UK rats( P P =0.001). What’s more, the sustain of the expression of TIMP-1( P =0.032) and Claudin5( P P P P =0.013) in PEG-UK treated rats were much less. Conclusions: Our findings indicated that treatment with PEG-UK ameliorated the severity of ischemic stroke, accompanied by neuroprotection through keeping the integrity of BBB and inhibiting apoptosis and neurotoxicity. PEG-UK may further inhibit hemorrhagic transformation by its BBB protection effect.

Introduction: High level of serum gut micro-devrived metabolite trimethylamine-N-oxide(TMAO) have recently been association with cardiovascular disease(CVD) and chronic kidney disease(CKD) risk. Hypothesis: Here, we aim to test the hypothesis that whether TMAO play a direct contributory role in progression of cerebral small disesase. Methods: First, we examined the plasma TMAO level in both subjects with and without cerebral small vessel diseases by liquid chromatography with on-line mass spectrometry (LC/MS) analysis. Further, SD rat were raised with either normal chow diet or normal chow diet supplemented with additional high amounts of TMAO. Animals were killed 14 weeks later and brains were preserved. Paraffin-embedded brain sections were stained using hematoxylin and eosin (HE), anti-claudin5 antibody and anti-ZO1 anti body. Results: It is reveals that TMAO level among cerebral small vessel disease is higher than that in normal control subjects. Results also shown that blood brain barrier was disrupted in high TMAO raised group and expression of tight juction proteins decreased. Sample size should be expanded in our following work. What’s more, cell model of blood brain barrier should be established to demonstrated the molecular mechanism of effect of TMAO. Conclusions: In conclusion, our study indicates that high serum level of TMAO is association with progression of cerebral small vessel diseases in poststroke patients and raised with diet supplemented with additional high amounts of TMAO lead to blood brain barrier disruption in vivo.

Background and Purpose— Limited information exists on the long-term consequences of stroke in China. We aimed to describe the profile and determinants of health-related quality of life among 12-month survivors of stroke. Methods— The ChinaQUEST (QUality Evaluation of Stroke care and Treatment) study was a prospective 62-hospital registry study of patients with acute stroke (ischemic stroke and intracerebral hemorrhage). Health-related quality of life was determined in 12-month survivors using a 35-item quality-of-life questionnaire (QOL-35) designed specifically for use in Chinese people. Proxy responses were used in those who were unable to personally complete the QOL-35. Results— A total of 4283 12-month stroke survivors completed assessments directly (1730 [40.4%]) or by a proxy (2553 [59.6%]). Mean (SD) health-related quality of life scores were higher in self-responders (70 [0.3] out of a best possible 100 score) than in proxy responders (60 [0.3]; P 19 000 CNY [approximately US $2714]; OR, 2.06; 95% CI, 1.37 to 3.10) and being disabled at discharge (OR, 3.65; 95% CI, 2.72 to 4.91). Proxy responders had similar predictive factors, including being disabled at discharge (OR, 4.99; 95% CI, 4.00 to 6.21), but income was not significant. Conclusions— In China, the strongest predictor of 12-month health-related quality of life after stroke is level of disability at hospital discharge. Level of income was another important factor. Health insurance schemes that offset the economic impact of stroke could help improve the health and well-being of Chinese people affected by stroke.

Background and Purpose— The prognostic significance of subarachnoid extension of intracerebral hemorrhage was determined in the INTEnsive blood pressure Reduction in Acute Cerebral hemorrhage Trial (INTERACT2) study. Methods— INTERACT2 was an open randomized controlled trial of early intensive compared with guideline-recommended blood pressure lowering in patients with elevated systolic blood pressure within 6 hours of intracerebral hemorrhage. Independent predictors of death or major disability (scores 3–6 on the modified Rankin Scale) at 90 days were analyzed in logistic regression models. Results— Of 2582 participants, 192 (7%) had subarachnoid extension, which was associated with larger hematoma volumes ( P P P P P =0.62). Conclusions— Subarachnoid extension of intracerebral hemorrhage is associated with poor prognosis, which is determined by a larger volume of the underlying intraparenchymal hematoma. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00716079.

Objective: The purpose of this study was to evaluate the safety and efficacy of hydroxyurea (HU) in spinal muscular atrophy (SMA) in a randomized, double-blind, placebo-controlled trial. Methods: Twenty-eight patients with type 2 SMA and 29 patients with type 3 SMA were randomly assigned (2:1) to receive HU or matching placebo for 18 months. HU was initiated at 10 mg/kg/day with an 8-week titration to 20 mg/kg/day. Subjects were assessed at baseline (T0) and monthly for the first 2 months (T1–T2) and then every 2 months throughout treatment (T3–T10) and posttreatment periods (T11–T13). The primary outcome measures were the Gross Motor Function Measure (GMFM), Manual Muscle Test (MMT), and serum full-length survivor motor neuron (flSMN) mRNA. The secondary outcome measures were Modified Hammersmith Functional Motor Scale and forced vital capacity (FVC). Results: Fifty-five patients completed this trial, which lasted from March 2007 to June 2009. Except for neutropenia, we found no differences in adverse events between the 2 groups. Compared with the placebo group, the HU group had −1.88 for GMFM (p = 0.11), −0.55 for MMT (p = 0.49), and 2.17 for flSMN mRNA (p = 0.13). Similarly, we found no difference in mean improvement of the secondary endpoints. Both groups had a trend toward a decline in FVC with little change in strength and motor function. Conclusion: Under the current regimen and schedule, HU brought about no improvement in patients with type 2 and 3 SMA, and its main side effect was neutropenia. Classification of evidence: This trial provides Class I evidence that HU 20 mg/kg/day does not effectively treat SMA.

The pilot phase of the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT) showed that rapid blood pressure (BP) lowering can attenuate hematoma growth in acute intracerebral hemorrhage. We sought to define the systolic BP level associated with greatest attenuation of hematoma growth. INTERACT included 404 patients with computed tomographic–confirmed intracerebral hemorrhage, elevated systolic BP (150 to 220 mm Hg), and capacity to commence BP lowering treatment within 6 hours of onset. Computed tomography was done at baseline and at 24 hours using standardized techniques, with digital images analyzed centrally, blinded to clinical data. Associations of baseline and achieved on-treatment (mean during the first 24 hours) systolic BP levels with the primary outcome of increase in hematoma volume were explored. There were 346 patients with duplicate computed tomographic scans. There was no significant association between baseline systolic BP levels and either the absolute or proportional growth in hematoma volume ( P trend=0.26 and 0.12, respectively). By contrast, achieved on-treatment systolic BP levels in the first 24 hours were clearly associated with both absolute and proportional hematoma growth (both P trend=0.03). Maximum reduction in hematoma growth occurred in the one third of participants with the lowest on-treatment systolic BP levels (median: 135 mm Hg). Intensive BP reduction to systolic levels between 130 and 140 mm Hg is likely to provide the maximum protection against hematoma growth after intracerebral hemorrhage.

Background and Purpose— We aimed to describe the uptake of proven secondary prevention strategies for ischemic stroke in urban China. Methods— In a prospective, multicenter, hospital-based registry of 4782 cases of acute ischemic stroke in China during 2006, the use of secondary prevention regimens was evaluated before hospital discharge and 3 and 12 months after stroke. Logistic regression analysis was performed to determine associations between various baseline variables and in-hospital use of antihypertensive, antiplatelet, and lipid-lowering therapies, and to identify variables associated with their continuation at 12 months. Results— In-hospital initiation of antihypertensive (63%), antiplatelet (81%), and lipid-lowering (31%) therapies was influenced favorably by previous use and comorbid cardiovascular risk factors and unfavorably by stroke severity. Antihypertensive use was well-maintained during follow-up, whereas use of antiplatelet and lipid-lowering therapy decreased (66% and 17%, respectively; P Interpretation— There was a high level of uptake of secondary prevention for ischemic stroke in this nationwide sample of hospitalized patients in urban China. However, use of antiplatelet and lipid-lowering therapy declined substantially after discharge, apparently related to misperceptions of subsequent disease risk by both doctors and patients.

Background and Purpose— The Intensive Blood Pressure Reduction In Acute Cerebral Haemorrhage Trial (INTERACT) study suggests that early intensive blood pressure (BP) lowering can attenuate hematoma growth at 24 hours after intracerebral hemorrhage. The present analyses aimed to determine the effects of treatment on hematoma and perihematomal edema over 72 hours. Methods— INTERACT included 404 patients with CT-confirmed intracerebral hemorrhage, elevated systolic BP (150 to 220 mm Hg), and capacity to start BP-lowering treatment within 6 hours of intracerebral hemorrhage. Patients were randomly assigned to an intensive (target systolic BP 140 mmHg) or standard guideline-based management of BP (target systolic BP 180 mm Hg) using routine intravenous agents. Baseline and repeat CTs (24 and 72 hours) were performed using standardized techniques with digital images analyzed centrally. Outcomes were increases in hematoma and perihematomal edema volumes over 72 hours. Results— Overall, 296 patients had all 3 CT scans available for the hematoma and 270 for the edema analyses. Mean systolic BP was 11.7 mm Hg lower in the intensive group than in the guideline group during 1 to 24 hours. Adjusted mean absolute increases in hematoma volumes (mL) at 24 and 72 hours were 2.40 and 0.15 in the guideline group compared with −0.74 and −2.31 in the intensive group, respectively, an overall difference of 2.80 (95% CI, 1.04 to 4.56; P =0.002). Adjusted mean absolute increases in edema volumes (mL) at 24 and 72 hours were 6.27 and 10.02 in the guideline group compared with 4.19 and 7.34 in the intensive group, respectively, for an overall difference of 2.38 (95% CI, −0.45 to 5.22; P =0.10). Conclusion— Early intensive BP-lowering treatment attenuated hematoma growth over 72 hours in intracerebral hemorrhage. There were no appreciable effects on perihematomal edema.

Rationale An acute presentation with diffuse magnetic resonance imaging lesions can have a broad differential. Demyelination and malignancy are important considerations. Therefore, sometimes it is hard to differentiate glioma from some demyelinating diseases solely on imaging because of the similar clinical presentation and imaging features. Detection of highly specific serum autoantibody marker aquaporin-4 (AQP4)-IgG positivity has helped to define a category of neuromyelitis optica spectrum disorders (NMOSD), but the test of AQP4 antibody has not been reported in patients with glioma. Patients concerns and diagnoses We report a case of a 56-year-old woman with cerebrospinal fluid (CSF) positive aquaporin-4 antibodies with initial response to immune therapy and secondary deterioration. A surgical biopsy revealed an anaplastic astrocytoma. Interventions and outcomes After the admission the patient was treated with a short course of intravenous steroid agents. After anaplastic astrocytoma was diagnosed, she began to receive a radiation treatment and soon later experienced a clinical deterioration with frequent epilepsy seizure and disturbance of consciousness within a few months. Lesson This case indicates that tumors could lead to polyclonal antibody responses as in this case with aquaporin-4 and myelin oligodendrocyte glycoprotein antibodies. The absence of a typical clinical phenotype and lack of sustained response to immunotherapy should alert the clinical suspicion of an alternative diagnosis. When AQP4 antibody was detected positive in CSF of a patient but negative in serum, differential diagnosis should especially be considered.

Background and Purpose— Stroke is a major health burden in China, but there are limited data on its economic effects on households. We aimed to examine the economic impact of stroke and to assess the influence of health insurance. Methods— In a nationwide, prospective, 62-hospital registry study of acute stroke in China, we recorded information on patient demographics, clinical features, socioeconomic factors, management, and costs of medical care. Information on out-of-pocket health expenses was obtained in surviving patients at 3- and 12-month follow-up. Catastrophic healthcare payments, defined as ≥30% of total household annual income, were estimated from reported household annual income. Results— Among 4739 3-month survivors of stroke with outcome data, average hospital and medication costs were 16 525 Chinese Yuan Renminbi (US $2361) and out-of-pocket costs were 14 478 Chinese Yuan Renminbi (US $2068). Overall, 3384 (71%) patients had experienced catastrophic out-of-pocket expenditure. Workers without health insurance were 7 times (OR, 6.9; 95% CI, 4.6 to 10.3) more likely to experience catastrophic payments than workers with insurance. Health insurance also protected against catastrophic payments in patients who were either retired or not working (no insurance: OR, 4.7; 95% CI, 3.1 to 7.2; OR, 1.82; 95% CI, 1.3 to 2.6, respectively). Conclusions— Because healthcare costs are high relative to income in China, families face considerable economic hardship after stroke. Health insurance protects families against catastrophic healthcare payments, thus highlighting the need to accelerate the ongoing process of building a comprehensive healthcare system in both urban and rural settings in China.

We studied 590 asymptomatic villagers aged > or =40 years in Liangbei County in central rural China and found 41 subjects (prevalence 6.9%) with intracranial atherosclerosis. In a multivariate analysis, the significant risk factors for intracranial stenosis were hypertension (OR 2.53; 95% CI 1.12 to 5.72), glycosuria (OR 3; 1.19 to 7.97), heart disease (OR 4; 1.39 to 11.6), and family history of stroke (OR 5.2; 1.38 to 20). Intracranial atherosclerosis is not uncommon among asymptomatic Chinese subjects.

Introduction: Debates exist in the impact of overweight and obesity on the outcome after stroke. Our study is aimed to investigate the relation between body mass index(BMI) and stroke outcome in a broad range of hospitalized patients with acute ischemic stroke in China. Methods: Data are from the ChinaQUEST (QUality Evaluation of Stroke Care and Treatment) study, a multi-centre, prospective, 62-hospital registry in China during 2006-07. Patients were categorized as underweight(BMI Results: There were 4782 patients with acute ischemic stroke enrolled in ChinaQUEST registry study. According to BMI, 282(5.9%) patients were of underweight, 2889(60.4%) were of normal weight, 1408(29.4%) were of overweight, and 203(4.2%) were obese. Outcome measures at 12 months were available in 4645 patients. The mortality was 21.3%(58/272) for underweight group, 10.6%(299/2810) for normal weight group, 8.5%(116/1365) for overweight group and 9.1%(18/198) for obesity group. The corresponding proportion of death or dependency was 45.6%(124/272), 30.9%(867/2810), 28.1%(384/1365) and 29.3%(58/198), respectively. After adjustment for all confounders, compared with patients of normal weight, odds ratio(95% confidence interval) of death at 12 months was 1.985(1.373-2.868) for underweight group, 0.952(0.738-1.229) for overweight group and 0.844(0.468-1.522) for obesity group. The corresponding odds ratio(95% confidence interval) of death or dependency at 12 months was 1.541(1.155-2.054), 1.004(0.853-1.181) and 0.837(0.578-1.211), respectively. Conclusion: In ischemic stroke patients, a J-shaped relationship between BMI and stroke outcome was observed. Underweight was associated with the highest risk for unfavorable outcome. No benefit of overweight and obesity on the survival or functional outcome over normal weight was found.

Background and purpose: Intraventricular haemorrhage (IVH) predicts outcome in acute intracerebral haemorrhage (ICH), but there is uncertainty over the strength of association and what clinically relevant threshold volume is relevant to prognosis. We aimed to elucidate risk associations of IVH and outcome in participants of the INTERACT2 study. Methods: INTERACT2 was an international, multicenter, prospective, open, blinded endpoint, randomized controlled trial of 2839 patients with ICH (3) at 90 days, were determined in logistic regression models. Results: Patients with ICH-IVH were significantly older, had greater clinical severity, and more with prior ischemic stroke and deep and large hematoma volume, after adjustment for other variables. Poor outcome occurred in 67% of ICH-IVH patients compared with 49% of ICH-alone patients (odds ratio [OR] 0.5, 95% confidence interval [CI] 0.42-0.60; p Conclusion: While a linear relation exists between IVH and outcome in ICH, a 5-10mL volume appears an appropriate cut-point for clinical-decisions over use of interventions with risk.

Background and Purpose— The goal of this article is to clarify the proportion of stroke subtypes in China, where stoke is the most common cause of death. Methods— A total of 16 031 first-ever strokes in subjects ≥25 years of age were identified in 1991 to 2000 from 17 Chinese populations through a community-based cardiovascular disease surveillance program in the China Multicenter Collaborative Study of Cardiovascular Epidemiology. World Health Organization diagnosis criteria were used for classification of stroke subtypes. Results— CT scan rate of stroke cases reached a satisfactorily high level only after 1996 in the study populations. In 8268 first-ever stroke events from 10 populations with CT scan rate >75% in 1996 to 2000, 1.8% were subarachnoid hemorrhage, 27.5% were intracerebral hemorrhage, 62.4% were cerebral infarction, and 8.3% were undetermined stroke. The proportion of intracerebral hemorrhage varied from 17.1% to 39.4% and that for cerebral infarction varied from 45.5% to 75.9% from population to population. The ratio of ischemic to hemorrhagic stroke ranged from 1.1 to 3.9 and averaged 2.0). The 28-day fatality rate was 33.3% for subarachnoid hemorrhage, 49.4% for intracerebral hemorrhage, 16.9% for cerebral infarction, and 64.6% for undetermined stroke. Conclusions— In our study, ischemic stroke was more frequent and its proportion was higher than hemorrhagic stroke in Chinese populations. Although hemorrhagic stroke was more frequent in Chinese than in Western populations, the variation in the proportion of stroke subtypes among Chinese populations could be as large as or larger than that between Chinese and Western populations.

Background and Purpose— The INTEnsive blood pressure Reduction in Acute Cerebral hemorrhage Trial (INTERACT) pilot study showed that early intensive blood pressure-lowering can attenuate hematoma growth in acute intracerebral hemorrhage. The present analysis aimed to determine the treatment effects on hematoma growth by time from intracerebral hemorrhage onset to randomization. Methods— Patients (N=404) with acute intracerebral hemorrhage and elevated systolic blood pressure were randomly assigned to intensive or guideline-based blood pressure management. Baseline and repeat CT (24 and 72 hours) were performed and changes in hematoma volume were assessed using generalized estimating equations. Results— Among 296 patients with all 3 CT scans available for analysis, reductions in proportional hematoma growth produced by randomized intensive blood pressure-lowering treatment over 72 hours decreased progressively with delays in initiation of study treatment: 22%, 17%, 9%, and 3% for quartile groups defined by time from onset to randomization of P trend=0.001). There were also smaller absolute reductions in hematoma growth with delays in initiation of study treatment (6.5 mL, 3.3 mL, 0.9 mL, and 0.6 mL), although the trend did not reach statistical significance ( P trend=0.12). Conclusions— Earlier initiation of intensive blood pressure-lowering treatment is likely to provide greater protection against hematoma growth in acute intracerebral hemorrhage. Clinical Trial Registration Information— http://www.clinicaltrials.gov , NCT002226096.

Purpose: Manual rating of Cerebral microbleeds (CMBs) is time-consuming and inconsistent. Since the presence and number of CMBs have become a potential diagnostic and prognostic biomarker of stroke, an automatic identification method is required. We proposed a computer aided diagnosis (CAD) system for the detection of the CMBs on the magnetic resonance (MR) images automatically. Methods: Eighty-one patients were recruited in this study. CMBs on the MR T2* weighted images were manually rated according to the Microbleed Anatomic Rating Scale (MARS) criteria. Our automated method consisted of two steps: i) Pre-processing: After skull stripping, isolated islands of points were removed while holes were restored to avoid over segmentation. Local threshold segmentation was applied for the initial candidate selection. ii) Identification model: Seven features were extracted from each candidate: area, roundness, intensity, average of the boundary, contrast, shape-intensity and location-mark (according to the probability density templates calculated from the location information of the CMBs). For further identification of each candidate, Random Forest (RF) model was used to distinguish CMBs from the mimics. Results: A total of 337 CMBs in the 81 patients were studied. Comparing with the counting from the experienced doctors, high sensitivity of 92% (310/337) was achieved after pre-processing. The RF model eliminated most of the false-positives while maintaining a reliable sensitivity of 94% (291/310) and specificity of 96% (4272/4450). The area under the Receiver operating characteristic curve was 0.98 ± 0.02 for the detection model. In summary, this CAD system had an overall sensitivity of 86% (291/337) and specificity of 96% (4272/4450), producing only 2.2 false-positives per subject. Conclusion: This presented strategy is technically effective. The results indicate that it has the potential to be used for clinical detection of CMBs.

The development and innovation of new technique in metabonomics research and its application in medicine provides important resolution in screening biomarkers and targets for further investigation. The metabonomics research has unique advantages of facility, objection and reliability compared with other -omics studies. Lipidomics research was development based on metabonomics and has supreme merits in study of lipids related disease. Method: The carotid arthrosclerosis patients with stroke suffered before were recruited in this research. The items of lipid related laboratory examinations of these patients are normal because of well controlling under drug-taken. The peripheral blood of these patients was drawn and the plasma was isolated after centrifugation. The lipids from plasma were extracted by the standard Folch method. Then the lipids samples were injected for lipid profile analysis by 2D QoF LC/MS. The qualitative differentiations of these lipids were based on their m/z value, characteristic of the compounds fragmentation, direct and relative retention time of each lipid class. On the establishment of the lipids identification, we validated this newly 2D QoF LC/MS method following these measurements including its calibration equations, low of the detection and relative standard deviation. Result: Compared with native subjects, 518 different types of lipids molecular from 17 classes were identified from plasma of atherosclerosis patients by the method of 2D QoF LC/MS; The galactosylceramide and glucoceramide were identified separately although they were same of molecular weight; We proved that the levels of galactosylceramide, rather than glucoceramide were increasing in atherosclerotic stroke patients. Conclusion: the increasing levels of galactosylceramide in plasma of atherosclerosis patients hint that the immune effects induced by lipids play an important role in atherosclerosis.

Objectives It has been reported that aspirin is effective for primary stroke prevention in women, but not men. Here, we conducted subgroup analysis of pooled results of Cilostazol versus Aspirin for Secondary Ischemic Stroke Prevention [CASISP] in China (Lancet Neurol 7: 494 - 499, 2008) and Cilostazol Stroke Prevention Study 2 [CSPS 2] in Japan (Lancet Neurol 9: 959 - 968, 2010) to evaluate gender differences in the effects of cilostazol and aspirin in secondary stroke prevention. Methods The analysis included 2410 men (cilostazol 1200, aspirin 1210) and 981 women (cilostazol 497, aspirin 484) from the two independent studies. Incidences of stroke as well as baseline patient characteristics, were compared between men and women in each group. Subgroup analysis, with stroke as an endpoint, was also conducted regarding age (≥60 yrs vs Results At baseline, the rates of patients with smoking and drinking habits and with diabetes mellitus were higher in men versus women, and the rates of older (≥60 yrs) patients and those with hypertension and dyslipidemia were higher in women versus men in both the cilostazol group and aspirin group. However, there was no significant difference in the baseline characteristics of men or of women between the cilostazol and aspirin groups. In men, stroke was significantly reduced by cilostazol versus aspirin (cilostazol 2.89%/person·year, aspirin 4.50%/person·year; p=0.0032). But, in women, aspirin was slightly, though not significantly, more effective than cilostazol (2.40% vs. 2.66%; p=0.7498). Intracranial hemorrhage was also significantly reduced in men by cilostazol versus aspirin (p Conclusions Gender differences in efficacy of antiplatelet agents appear to exist for secondary stroke prevention. Cilostazol was more effective in men, but aspirin may be the first choice drug for women.