Search

Introduction: The triglyceride-glucose (TyG) index is reported to be related to poor functional outcomes and all-cause mortality post-stroke. However, the association between TyG index and recurrent stroke after acute ischemic stroke (AIS) has not been well described. We aimed to identify whether the TyG index was associated with 1-year recurrent stroke after AIS. Methods: Baseline patient information was collected at admission, and the TyG index was calculated. Recurrent stroke events were followed up at 1, 3, 6, and 12 months after diagnosis. We then examined the association between the TyG index and risk of 1-year recurrent stroke using multivariable Cox regression models and restricted cubic spline analyses. Results: Among 2,288 participants, the mean TyG index was 8.8 ± 0.7. Those in the fourth quartile (Q4) demonstrated higher recurrent stroke risk than those in Q1 (adjusted hazard ratio [HR] = 1.63; 95% confidence interval [CI], 0.98–2.72; p = 0.059). Subgroup analysis revealed a sex-specific association between TyG index and recurrent stroke (p for interaction = 0.022). Additionally, restricted cubic splines analyses showed a nonlinear association between the TyG index and 1-year recurrent stroke. In females, patients in the Q4 had a 2.95-fold increased recurrent stroke risk than did patients in the Q1 (adjusted HR = 2.95; 95% CI: 1.09–7.94; p = 0.032); the risk increased when the TyG index was >8.73. However, no significant correlation was observed in males. Conclusion: A nonlinear association was found between the TyG index and 1-year recurrent stroke risk. Subsequently, a high TyG index could predict an increased 1-year recurrent stroke risk in female AIS patients. [ABSTRACT FROM AUTHOR]

Background: Stroke is an important cause of death and disability worldwide, ranking second in the cause of death, and it is thought to be related to genetic factors. The purpose of our study is to investigate the association between CASZ1, WNT2B and PTPRG single nucleotide polymorphisms (SNPs) and stroke risk in the Chinese population. Methods: We recruited 1418 volunteers, comprised of 710 stroke cases and 708 controls in this study. We used MassARRAY iPLEX GOLD method to genotype the three SNPs on CASZ1, WNT2B and PTPRG. Logistic regression was used to analyse the association between these SNPs and stroke, and odds ratios (ORs) and 95% confidence intervals (CIs) were then calculated. What's more, the interactions among SNPs were predicted by multi‐factor dimensionality reduction (MDR) analysis. Results: This research demonstrated that CASZ1 rs880315 and PTPRG rs704341 were associated with reduced stroke susceptibility. More precisely, CASZ1 rs880315 was associated with reduced stroke susceptibility in people aged ≤64 years and women. PTPRG rs704341 was associated with reduced stroke susceptibility in people aged >64 years, women, non‐smokers and non‐drinkers. Conversely, WNT2B rs12037987 was related to elevated stroke susceptibility in people aged >64 years, women and non‐smokers. In addition, CASZ1 rs880315, WNT2B rs12037987 and PTPRG rs704341 had a strong redundancy relationship. Conclusion: Our study concludes that CASZ1 rs880315, WNT2B rs12037987 and PTPRG rs704341 are associated with stroke, and the study provides a basis for assessing genetic variants associated with stroke risk in the Han Chinese population. [ABSTRACT FROM AUTHOR]

S100B is an essential biomarker in the early diagnosis and treatment monitoring of brain injury. However, the traditional clinical diagnostic assay for S100B detection requires a complex operation or large equipment, which limits its application for rapid point-of-care tests (POCT). This study aimed to establish a lateral-flow immunoassay (LFIA) strip test system for S100B determination. PSS-MA-GoldMag nanoparticles were conjugated with anti-S100B antibodies as probes. Using this antibody-nanoparticle composite, an LFIA system based on magnetic quantification was established for S100B detection. For the evaluation of the performance of this LFIA system in clinical practice, 216 clinical samples were assayed using the LFIA test system and a commercial ECLI kit. Using the LFIA system, reliable results could be obtained in 30 min with a detection limit of 0.05 ng mL−1. The coefficient of variation (CV) was <13.8% and <14.03% for intra- and inter-assay precision, respectively. The recoveries were between 95.1 and 107.3%. The relative deviation of the interference experiments was <10%. In the analysis of clinical samples, the result indicated that the sera level of S100B in the detection group did not correlate with gender (p = 0.564 > 0.05) or age (p = 0.083 > 0.05). There is a good correlation between the novel method and the Elecsys®, with a determination coefficient of R2 0.9566, p > 0.05. The Bland–Altman analysis between the two ways shows that the 95% confidence bands between the two methods in measuring S100B were −0.27 ng mL−1 to +0.29 ng mL−1 with a mean difference of +0.006 ng mL−1. These results indicated that the novel LFIA system could be a simple, rapid, convenient, and accurate method for S100B determination. [ABSTRACT FROM AUTHOR]

A nine-year-old boy manifested with headache, progressive mild cognitive decline and hemiparesis, but without clinical epileptic seizures (with abnormal EEG waves). Brain magnetic resonance imaging (MRI) showed bilateral cortical lesions mainly on the right hemisphere, and new lesions developed in frontal, parietal, occipital and temporal lobes around the old lesions presenting as a lace-like or ring-like enhancement in T1 with contrast over a disease course of five years. A suspected diagnosis of primary angiitis of the central nervous system was initially considered. Treated with high-dose corticosteroids, intravenous immunoglobulins and monthly pulse cyclophosphamide, his symptoms worsened with the intracranial lesion progression. Brain biopsy of the right frontal lobe was performed nearly five years after onset; prominent neuronal loss, a microglial nodule, as well as parenchymal and perivascular lymphocytic infiltrate within the cortex were found, which coincided with RE pathology changes. Encouragingly, after a regimen of rituximab, lesions on the follow-up brain MRI tended to be stable. Apparently, it was immune-mediated, but did not strictly fit any known disease entity, although it was similar to RE. We summarize this unique case, including clinical characteristics, imaging and pathology findings. We also discuss the diagnosis and treatment, focusing on comparison to RE as well as other possible neurological diseases. [ABSTRACT FROM AUTHOR]

Background: In recent years, alkaline phosphatase (ALP) has been considered as one of the independent risk factors of acute ischemic stroke (AIS) and leads to worse clinical outcomes in patients with renal failure. In this study, we aim to investigate whether serum ALP level is associated with poor early-term prognosis in relationship of AIS patients with preserved renal function.Methods: A prospectively collected database of AIS patients hospitalized in the Xi'an district of China from January to December, 2015 was analyzed. The demographics, serum ALP levels and stroke outcomes of all patients at 3 months were reviewed. Patients were routinely followed-up for 3 months. Serum ALP level was analyzed as a continuous variable and quintiles (Q1-Q5). Multivariate logistic regression model and a two-piecewise linear regression model were used to investigate the relationship and to determine the threshold effect regarding serum ALP levels and poor 3-month prognosis of AIS patients with preserved renal function.Results: Overall, 1922 AIS patients were enrolled with 62.3% of them being men. The risk of having a poor 3-month prognosis was significantly increased in Q1, Q2, Q3 and Q5, when compared to that in Q4 being as the reference. The highest risk was noted in Q5 (odds ratio 2.21, 95% confidence interval: 1.32-3.73, P = 0.003) after being adjusted for confounders. Further analysis revealed a J-shaped curvilinear relationship between ALP levels and a poor 3-month prognosis of strokes (optimal threshold ALP level = 90 U/L). The relationship between both parameters was not significantly affected by age, sex, drinking, hypertension and leukocyte count (stratified by 10 × 109/L) (P for interaction > 0.05).Conclusions: Serum ALP was noted as an independent risk factor for a poor 3-month prognosis of AIS patients with preserved renal function. ALP levels higher than 90 U/L could cause an increased risk of a poor 3-month prognosis. [ABSTRACT FROM AUTHOR]

Psoralidin (PSO) is a natural phenolic coumarin extracted from the seeds of Psoralea corylifolia L. Growing preclinical evidence indicates that PSO has anti‐inflammatory, anti‐vitiligo, anti‐bacterial, and anti‐viral effects. Growth arrest‐specific gene 6 (GAS6) and its receptor, Axl, modulate cellular oxidative stress, apoptosis, survival, proliferation, migration, and mitogenesis. Notably, the neuroprotective role of the GAS6/Axl axis has been identified in previous studies. We hypothesize that PSO ameliorates cerebral hypoxia/reoxygenation (HR) injury via activating the GAS6/Axl signaling. We first confirmed that PSO was not toxic to the cells and upregulated GAS6 and Axl expression after HR injury. Moreover, PSO exerted a marked neuroprotective effect against HR injury, represented by restored cell viability and cell morphology, decreased lactate dehydrogenase (LDH) release, and reactive oxygen species (ROS) generation. Furthermore, PSO pretreatment also elevated the levels of nuclear factor‐related factor 2 (Nrf‐2), NAD(P)H dehydrogenase quinone‐1 (NQO1), heme oxygenase‐1 (HO‐1), silent information regulator 1 (SIRT1), peroxisome proliferator‐activated receptor coactivator 1α (PGC‐1α), nuclear respiratory factor 1 (NRF1), uncoupling protein 2 (UCP2), and B‐cell lymphoma 2 (BCl2) both in the condition of baseline and HR injury. However, GAS6 siRNA or Axl siRNA inhibited the neuroprotective effects of PSO. Our findings suggest that PSO pretreatment attenuated HR‐induced oxidative stress, apoptosis, and mitochondrial dysfunction in neuroblastoma cells through the activation of GAS6/Axl signaling. [ABSTRACT FROM AUTHOR]

Background: To analyze disease generalization in patients with ocular myasthenia gravis (OMG) treated with immunosuppression compared with patients without immunosuppression treatment. Methods: In this retrospective cohort study, we analyzed data from patients with OMG at seven medical centers in China from January 1, 2015 to May 1, 2019 and compared disease generalization in patients (treated with immunosuppression vs. not treated) within 2 years of disease onset using raw and inverse probability of treatment weighting (IPTW) analyses. Results: In the study population of 813 patients with OMG, 425 (52.3%) with immunosuppression had a mean (SD) onset age of 50.0 (15.1) years, and 188 (44.2%) were women. The remaining 388 (47.7%) patients were not immunosuppressed (mean age, 48.4 [15.0] years; 185 [47.7%] women). Disease generalization developed in 122 (31.4%) and 37 (8.7%) patients in the non‐immunosuppression and immunosuppression groups, respectively. Relative to non‐immunosuppression, immunosuppression was associated with a lower risk of generalization in a multivariable‐adjusted Cox model (hazard ratio [HR] 0.27; 95% confidence interval [CI] 0.18–0.40; p < 0.001) and IPTW‐weighted Cox model (HR 0.28; 95% CI 0.19–0.42; p < 0.001). In sensitivity analyses, longer duration of immunosuppression was associated with a lower risk of generalization (HR 0.90 for every 1‐month increase; 95% CI 0.87–0.92; p < 0.001; IPTW‐adjusted). Combination therapy with steroids and non‐steroidal immunosuppressants showed superior efficacy in reducing the risk of generalization (HR 0.14; 95% CI 0.07–0.26; p < 0.001). Conclusion: Immunosuppression significantly reduced the 2‐year risk of generalization in patients with OMG. [ABSTRACT FROM AUTHOR]

Neuronal intranuclear inclusion disease (NIID) is a rare and slowly progressive neurodegenerative disease characterized by the presence of eosinophilic neuronal intranuclear inclusions. The clinical manifestations of NIID are diverse, and the most common initial feature in cases of sporadic NIID is dementia. Herein, we report an adult female with keratitis as the initial presentation with subsequent bilateral limb tremor, gait disturbances, overemotional behavior, sweating and constipation. Diffusion-weighted imaging (DWI) showed hyperintensity in the bilateral fronto-parieto-occipital corticomedullary junction. Skin biopsy specimens revealed eosinophilic hyaline intranuclear inclusions in fibroblast cells, sweat gland cells and adipose cells. In vivo confocal microscopy of the cornea indicated the absence of corneal nerves in both affected eyes. The patient's diagnosis of NIID was based on the presence of intranuclear inclusions in biopsied skin and the characteristic high-intensity signal in the corticomedullary junction obtained with DWI. This case report emphasizes that the clinical heterogeneity of NIID and an examination of the corneal nerves may offer valuable clues to its early diagnosis in some patients. [ABSTRACT FROM AUTHOR]

Background: The relationship between baseline fasting blood glucose (FBG) levels and 1-year stroke recurrence in non-diabetic patients with acute cerebral infarction (ACI) is unclear. We aimed to clarify this relationship in non-diabetic patients with ACI. Methods: Baseline FBG levels and related information of the patients were collected at admission and the events of stroke recurrence were followed up 1, 3, 6, and 12 months after the patients were discharged. Baseline FBG levels were analyzed as continuous variables and quartiles (Q1–Q4). Multivariate Cox regression models and a two-piecewise linear regression model were used to investigate the relationship and determine the threshold effect between baseline FBG levels and 1-year stroke recurrence in non-diabetic patients with ACI. Results: Overall, 1,634 non-diabetic patients with ACI were enrolled. After adjusting for potential confounding factors, the hazard is 2.24-fold higher in Q4 than those in Q2, being considered the reference in non-diabetic patients with ACI [hazard ratio (HR) = 2.24, 95%CI: 1.08–4.65, P = 0.031]. Plotting hazard ratios over baseline FBG levels suggested a J-shaped relationship for 1-year stroke recurrence. Further analysis revealed that the nadir value of baseline FBG levels is 4.6 mmol/L. The relationship was more significant in patients with atrial fibrillation than in those without (P for interaction = 0.009). Conclusion: Lower and higher baseline FBG levels may lead to an increased risk of 1-year stroke recurrence in non-diabetic patients with ACI as shown by a J-shaped curve with a nadir value of 4.6 mmol/L. [ABSTRACT FROM AUTHOR]

Anti-contactin-associated protein-like 2 (CASPR2) antibody-associated autoimmune encephalitis is commonly characterized by limbic encephalitis with clinical symptoms of mental and behavior disorders, cognitive impairment, deterioration of memory, and epilepsy. The classical lesions reported are located at the medial temporal lobe or hippocampus, whereas prominent brainstem lesions have not been addressed to date. Herein, we reported two patients mimicking progressive brainstem infarction with severe neurological manifestations. On brain magnetic resonance imaging (MRI), prominent brainstem lesions were noted, although multifocal lesions were also shown in the juxtacortical and subcortical white matters, basal ganglia, hippocampus, and cerebellar hemisphere. Unexpectedly and interestingly, both cases had detectable CASPR2 antibodies in sera, and an exclusive IgG1 subclass was documented in the further analysis. They were treated effectively with aggressive immunosuppressive therapies including corticosteroids, intravenous immunoglobulin G, and rituximab, with the first case achieving a rapid remission and the other undergoing a slow but gradual improvement. To the best of our knowledge, this is the first report on prominent brainstem involvement with definite MRI lesions in anti-CASPR2 antibody-associated autoimmune encephalitis, which helps to expand the clinical spectrum of this rare autoimmune disease and update the lesion patterns in the CNS. [ABSTRACT FROM AUTHOR]

This study aims to investigate the association between thymectomy and the risk of generalization in patients with ocular myasthenia gravis (MG). Data on patients with ocular MG from seven neurological centers in China were retrospectively reviewed. Ocular MG naïve to immunotherapy was categorized according to whether thymectomy was performed (thymectomized group vs. nonsurgical group). Patients in the thymectomized group all underwent surgery within 2 years since ocular symptom onset. The main outcome measure was the generalization. The follow-up period was defined from the date of ocular symptom onset to the date of generalization confirmation, immunotherapy initiation, or last follow-up (defined as 60 months). Of 519 eligible patients (mean [SD] age, 48.7 [15.2] years, 46.6% women), 31 (23.7%) of 131 generalized in the thymectomized group and 122 (31.4%) of 388 did in the nonsurgical group during a median follow-up of 19 months (IQR 8.0–50.0). Thymectomy was independently associated with reduced generalization risk (adjusted HR 0.41, 95% CI 0.25–0.66, P < 0.001). Multivariable stratified analysis also verified this association across the subgroups. Kaplan–Meier curves showed that the 5-year cumulative rate was significantly lower in the thymectomized group than in the nonsurgical group. To conclude, thymectomy may be considered effective in modifying the progression from ocular to generalized MG irrespective of thymoma. [ABSTRACT FROM AUTHOR]

Background: Dorsolateral medullary infarction is a typical cerebral infarction which is characterized by Wallenberg's syndrome. Neurotrophic keratopathy is an uncommon consequence of dorsolateral medullary infarction. At present, the protocol is aimed to study the dynamic changes in corneal innervation and the ocular surface environment after dorsolateral medullary infarction.Methods: This study will involve consecutive data from all medical records of patients within 7 days of acute dorsolateral medullary infarction onset at the Departments of Neurology from 10 collaborating stroke centers. Eligible patients will mainly be characterized based on detailed physical examinations, multimodal imaging, and corneal related examinations and patients will be followed-up for 2 years. Neurotrophic keratopathy after dorsolateral medullary infarction is the primary endpoint. The dynamic histological corneal innervation and ocular surface environment after dorsolateral medullary infarction will be observed during the follow-up period.Discussion: This multicentric, prospective registry is the first to identify and characterize the dynamic changes of corneal innervation and the ocular surface environment after acute dorsolateral medullary infarction. The significance of the study is to emphasize that the curative effect is based on the doctors' identification of the disease in the earliest stage before irreversible damage occurs to the cornea.Trial Registration: The registry was registered ( ChiCTR-OPC-17,011,625 ) on June 11, 2017. [ABSTRACT FROM AUTHOR]

Background: The prevalence of stroke recurrence, disability, and all-cause mortality of patients with minor ischemic stroke (MIS) remains problematic. The aim of the present study was to identify risk factors associated with adverse outcomes at 1 year after MIS in the Xi'an region of China.Methods: This prospective cohort study included MIS patients above 18 years old with National Institutes of Health Stroke Scale (NIHSS) score ≤ 3 who were treated in any of four hospitals in Xi'an region of China between January and December 2015. The 1-year prevalence of stroke recurrence, disability, and all-cause mortality were evaluated, respectively. Multivariate logistic regression analysis was performed to assess the association between the identified risk factors and clinical outcomes.Results: In this study, 131(10.5%, 131/1252) patients were lost to follow-up at 1 year. A total of 1121 patients were included for analysis, the prevalence of stroke recurrence, disability, and all-cause mortality at 1 year after MIS were 3.4% (38/1121), 9.3% (104/1121), and 3.3% (37/1121), respectively. Multivariate logistic regression analysis identified age, current smoking, and pneumonia as independent risk factors for stroke recurrence. Age, pneumonia, and alkaline phosphatase were independent risk factors for all-cause mortality. Independent risk factors for disability were age, pneumonia, NIHSS score on admission, and leukocyte count.Conclusions: The 1-year outcomes of MIS in Xi'an region of China were not optimistic, especially with a high prevalence of disability. The present study indicated that age and pneumonia were the common independent risk factors affecting the 1-year outcomes of MIS in Xi'an region of China. [ABSTRACT FROM AUTHOR]

Gold magnetic nanoparticles (GoldMag) have attracted great attention due to their unique physical and chemical performances combining those of individual FeO and Au nanoparticles. Coating GoldMag with polymers not only increases the stability of the composite particles suspended in buffer but also plays a key role for establishing point-of-care optical tests for clinically relevant biomolecules. In the present paper, poly(4-styrenesulfonic acid-co-maleic acid) (PSS-MA), a negatively charged polyelectrolyte with both sulfonate and carboxylate anionic groups, was used to coat the positively charged GoldMag (30 nm) surface. The PSS-MA-coated GoldMag complex has a stable plasmon resonance adsorption peak at 544 nm. A pair of anti-D-dimer antibodies has been coupled on this GoldMag composite nanoparticle surface, and a target protein, D-dimer was detected, in the range of 0.3-6 μg/mL. The shift of the characteristic peak, caused by the assembly of GoldMag due to the formation of D-dimer-antibody sandwich bridges, allowed the detection. [ABSTRACT FROM AUTHOR]

Neuronal oxidative stress (OS) injury has been proven to be associated with many neurodegenerative diseases, and thus, antioxidation treatment is an effective method for treating these diseases. Saikosaponin-D (SSD) is a sapogenin extracted from Bupleurum falcatum and has been shown to have many pharmacological activities. The main purpose of this study was to investigate whether and how SSD protects PC12 cells from HO-induced apoptosis. The non-toxic level of SSD significantly mitigated the HO-induced decrease in cell viability, reduced the apoptosis rate, improved the nuclear morphology, and reduced caspase-3 activation and poly ADP-ribose polymerase (PARP) cleavage. Additionally, exogenous HO-induced apoptosis by damaging the intracellular antioxidation system. SSD significantly slowed the HO-induced release of malonic dialdehyde (MDA) and lactate dehydrogenase and increased the activity of superoxide dismutase (SOD) and the total antioxidant capacity, thereby reducing apoptosis. More importantly, SSD effectively blocked HO-induced phosphorylation of extracellular-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38MAPK), and specific inhibitors of ERK, JNK, and p38-reduced OS injury and apoptosis, suggesting that SSD reduces OS injury and apoptosis via MAPK signalling pathways. Finally, we confirmed that SSD significantly reduced HO-induced reactive oxygen species (ROS) accumulation, and the ROS inhibitor blocked the apoptosis caused by MAPK activation and cellular oxidative damage. In short, our study confirmed that SSD reduces HO-induced PC12 cell apoptosis by removing ROS and blocking MAPK-dependent oxidative damage. [ABSTRACT FROM AUTHOR]

Rationale Epidemiological studies suggest that elevated homocysteine is linked to stroke and heart disease. However, the results of lowering homocysteine levels in reducing the risk of stroke recurrence are controversial. Aims The study aims to evaluate whether homocysteine-lowering therapy with folic acid and vitamins B6 and B12 reduces recurrent stroke events and other combined incidence of recurrent vascular events and vascular death in ischemic stroke patients of low folate regions. Design This is a multicenter, randomized, double-blinded, placebo-controlled trial. Patients ( n = 8000, α = 0·05, β = 0·10) within one-month of ischemic stroke (large-artery atherosclerosis or small-vessel occlusion) or hypertensive intracerebral haemorrhage with plasma homocysteine level ≥15 μmol/l will be enrolled. Eligible patients will be randomized by a web-based, random allocation system to receive multivitamins (folic acid 0·8 mg, vitamin B 6 10 mg, and vitamin B 12 500 μg) or matching placebo daily with a median follow-up of three-years. Study Outcomes Patients will be evaluated at six monthly intervals. The primary outcome event is the composite event 'stroke, myocardial infarction, or death from any vascular cause', whichever occurs first. Secondary outcome measures include nonvascular death, transient ischemic attack, depression, dementia, unstable angina, revascularization procedures of the coronary, and cerebral and peripheral circulations. Discussion This is the first multicenter randomized trial of secondary prevention for ischemic stroke in a Chinese population with a higher homocysteine level but without folate food fortification. [ABSTRACT FROM AUTHOR]

Background: Dorsolateral medullary infarction (Wallenberg syndrome) is rare in clinical practice; however, the subsequent corneal lesions are more uncommon. To our knowledge, only one such case was previously reported. We report a similar case with successful treatment and recovery, and analyse both cases to address the clinical features and outcomes of such syndrome.Case Presentation: A 43-year-old male presented with neurotrophic keratopathy one month after sustaining dorsolateral medullary infarction. The patient underwent amniotic membrane transplantation twice. Two-year follow-up observation revealed changes in nerve fibers and epithelial cells of corneal by laser confocal microscopy.Conclusion: By studying both cases, we confirm that neurotrophic keratopathy could be as a delayed-onset complication of Wallenberg syndrome. The recognition that neurotrophic keratopathy can follow dorsolateral medullary infarction could prevent the clinical misdiagnosis. [ABSTRACT FROM AUTHOR]