Publications by authors named "Jinsheng Zeng"

120 Publications

Machine Learning for Predicting Motor Improvement After Acute Subcortical Infarction Using Baseline Whole Brain Volumes.

Neurorehabil Neural Repair 2021 Nov 1:15459683211054178. Epub 2021 Nov 1.

Department of Electrical and Electronic Engineering, 255310Southern University of Science and Technology, Shenzhen, China.

Neuroimaging biomarkers are valuable predictors of motor improvement after stroke, but there is a gap between published evidence and clinical usage. In this work, we aimed to investigate whether machine learning techniques, when applied to a combination of baseline whole brain volumes and clinical data, can accurately predict individual motor outcome after stroke. Upper extremity Fugl-Meyer Assessments (FMA-UE) were conducted 1 week and 12 weeks, and structural MRI was performed 1 week, after onset in 56 patients with subcortical infarction. Proportional recovery model residuals were employed to assign patients to proportional and poor recovery groups (34 vs 22). A sophisticated machine learning scheme, consisting of conditional infomax feature extraction, synthetic minority over-sampling technique for nominal and continuous, and bagging classification, was employed to predict motor outcomes, with the input features being a combination of baseline whole brain volumes and clinical data (FMA-UE scores). The proposed machine learning scheme yielded an overall balanced accuracy of 87.71% in predicting proportional vs poor recovery outcomes, a sensitivity of 93.77% in correctly identifying poor recovery outcomes, and a ROC AUC of 89.74%. Compared with only using clinical data, adding whole brain volumes can significantly improve the classification performance, especially in terms of the overall balanced accuracy (from 80.88% to 87.71%) and the sensitivity (from 92.23% to 93.77%). Experimental results suggest that a combination of baseline whole brain volumes and clinical data, when equipped with appropriate machine learning techniques, may provide valuable information for personalized rehabilitation planning after subcortical infarction.
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http://dx.doi.org/10.1177/15459683211054178DOI Listing
November 2021

Population-Average Brain Templates and Application to Automated Voxel-Wise Analysis Pipelines for Cynomolgus Macaque.

Neuroinformatics 2021 Sep 14. Epub 2021 Sep 14.

Department of Neurology and Stroke Center, Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital, Sun Yat-Sen University, National Key Clinical Department and Key Discipline of Neurology, No. 58 Zhongshan Road 2, Guangzhou, 510080, China.

The growing number of neuroimaging studies of cynomolgus macaques require extending existing templates to facilitate species-specific application of voxel-wise neuroimaging methodologies. This study aimed to create population-averaged structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) templates for the cynomolgus macaques and apply the templates in fully automated voxel-wise analyses. We presented the development of symmetric and asymmetric MRI and DTI templates from a sample of 63 young male cynomolgus monkeys with the use of optimized template creation approaches. We also generated the associated average tissue probability maps and Diffeomorphic Anatomical Registration using Exponentiated Lie Algebra templates for use with the Statistical Parametric Mapping (SPM), as well as the average fractional anisotropy/skeleton targets for incorporation into tract-based spatial statistics (TBSS) framework. Both asymmetric and symmetric templates in a standardized coordinate space demonstrated low bias and high contrast. Fully automated processing using SPM was accomplished for all native MRI datasets and demonstrated outstanding performance regarding skull-stripping, segmentation, and normalization when using the MRI templates. Automated normalization to the DTI template was excellently achieved for all native DTI images using the TBSS pipeline. The cynomolgus MRI and DTI templates are anticipated to provide a common platform for precise single-subject data analysis and facilitate comparison of neuroimaging findings in cynomolgus monkeys across studies and sites. It is also hoped that the procedures of template creation and fully-automated voxel-wise frameworks will provide a straightforward avenue for investigating brain function, development, and neuro-psychopathological disorders in non-human primate models.
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http://dx.doi.org/10.1007/s12021-021-09545-4DOI Listing
September 2021

Nervous and Muscular Adverse Events after COVID-19 Vaccination: A Systematic Review and Meta-Analysis of Clinical Trials.

Vaccines (Basel) 2021 Aug 23;9(8). Epub 2021 Aug 23.

Department of Neurology, The First Affiliated Hospital, Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, Sun Yat-sen University, Guangzhou 510080, China.

Nervous and muscular adverse events (NMAEs) have garnered considerable attention after the vaccination against coronavirus disease (COVID-19). However, the incidences of NMAEs remain unclear. We aimed to calculate the pooled event rate of NMAEs after COVID-19 vaccination. A systematic review and meta-analysis of clinical trials on the incidences of NMAEs after COVID-19 vaccination was conducted. The PubMed, Medline, Embase, Cochrane Library, and Chinese National Knowledge Infrastructure databases were searched from inception to 2 June 2021. Two independent reviewers selected the study and extracted the data. Categorical variables were analyzed using Pearson's chi-square test. The pooled odds ratio (OR) with the corresponding 95% confidence intervals (CIs) were estimated and generated with random or fixed effects models. The protocol of the present study was registered on PROSPERO (CRD42021240450). In 15 phase 1/2 trials, NMAEs occurred in 29.2% vs. 21.6% ( < 0.001) vaccinated participants and controls. Headache and myalgia accounted for 98.2% and 97.7%, and their incidences were 16.4% vs. 13.9% (OR = 1.97, 95% CI = 1.28-3.06, = 0.002) and 16.0% vs. 7.9% (OR = 3.31, 95% CI = 2.05-5.35, < 0.001) in the vaccine and control groups, respectively. Headache and myalgia were more frequent in the newly licensed vaccines (OR = 1.97, 95% CI = 1.28-3.06, = 0.02 and OR = 3.31, 95% CI = 2.05-5.35, < 0.001) and younger adults (OR = 1.40, 95% CI = 1.12-1.75, 0.003 and OR = 1.54, 95% CI = 1.20-1.96, < 0.001). In four open-label trials, the incidences of headache, myalgia, and unsolicited NMAEs were 38.7%, 27.4%, and 1.5%. Following vaccination in phase 3 trials, headache and myalgia were still common with a rate of 29.5% and 19.2%, although the unsolicited NMAEs with incidence rates of ≤ 0.7% were not different from the control group in each study. Following the vaccination, NMAEs are common of which headache and myalgia comprised a considerable measure, although life-threatening unsolicited events are rare. NMAEs should be continuously monitored during the ongoing global COVID-19 vaccination program.
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http://dx.doi.org/10.3390/vaccines9080939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402736PMC
August 2021

Longitudinal changes in the inferior cerebellar peduncle and lower limb motor recovery following subcortical infarction.

BMC Neurol 2021 Aug 17;21(1):320. Epub 2021 Aug 17.

Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University; Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, No. 58, Zhongshan Road 2, Guangzhou, Guangdong, China.

Background: The cerebellum receives afferent signals from spinocerebellar pathways regulating lower limb movements. However, the longitudinal changes in the spinocerebellar pathway in the early stage of unilateral supratentorial stroke and their potential clinical significance have received little attention.

Methods: Diffusion tensor imaging and Fugl-Meyer assessment of lower limb were performed 1, 4, and 12 weeks after onset in 33 patients with acute subcortical infarction involving the supratentorial areas, and in 33 healthy subjects. We evaluated group differences in diffusion metrics in the bilateral inferior cerebellar peduncle (ICP) and analyzed the correlation between ICP diffusion metrics and changes to the Fugl-Meyer scores of the affected lower limb within 12 weeks after stroke.

Results: Significantly decreased fractional anisotropy and increased mean diffusivity were found in the contralesional ICP at week 12 after stroke compared to controls (all P < 0.01) and those at week 1 (all P < 0.05). There were significant fractional anisotropy decreases in the ipsilesional ICP at week 4 (P = 0.008) and week 12 (P = 0.004) compared to controls. Both fractional anisotropy (r = 0.416, P = 0.025) and mean diffusivity (r = -0.507, P = 0.005) changes in the contralesional ICP correlated with changes in Fugl-Meyer scores of the affected lower limb in all patients.

Conclusions: Bilateral ICP degeneration occurs in the early phase of supratentorial stroke, and diffusion metric values of the contralesional ICP are useful indicators of affected lower limb function after supratentorial stroke.
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http://dx.doi.org/10.1186/s12883-021-02346-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369783PMC
August 2021

Association between aspirin-induced hemoglobin decline and outcome after acute ischemic stroke in G6PD-deficient patients.

CNS Neurosci Ther 2021 10 8;27(10):1206-1213. Epub 2021 Aug 8.

Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China.

Aims: The risk of hemoglobin decline induced by low-dose aspirin in glucose-6-phosphate dehydrogenase (G6PD) deficiency remains unknown, and its influence on stroke outcome remains to be investigated. This study aimed to evaluate the effect of G6PD deficiency on hemoglobin level during aspirin treatment and its association with outcome after acute ischemic stroke.

Methods: In total, 279 patients (40 G6PD-deficient and 239 G6PD-normal) with acute ischemic stroke treated with aspirin 100 mg/day from a cohort study were examined. The primary safety endpoint was a hemoglobin decline ≥25 g/L or 25% from baseline within 14 days after aspirin treatment. Poor outcomes were defined as a modified Rankin Scale score ≥2 at 3 months. The χ test was used to compare stroke outcomes, and multivariate logistic regression analyses were performed to analyze the association between hemoglobin level and outcomes.

Results: The G6PD-deficient group had lower baseline hemoglobin and tended to develop comorbid pulmonary infection more frequently (p < 0.05). The proportion of patients with hemoglobin decline ≥25 g/L or 25% from baseline (15.0% vs. 3.3%; p = 0.006) and anemia (30.0% vs. 14.6%; p = 0.016) after aspirin treatment was higher in the G6PD-deficient group, which was accompanied by a more significant bilirubin increase. The rate of poor functional outcomes at 3 months after acute ischemic stroke was higher in the G6PD-deficient group (Risk ratio = 1.31 [95% confidence interval (CI) = 1.10-1.56]; p = 0.017). Confounder-adjusted analysis showed that lower hemoglobin levels (odds ratio = 0.98 [95% CI = 0.96-0.99]; adjusted p = 0.009) increased the risk of poor functional outcomes.

Conclusion: Hemoglobin decrease with bilirubin increase after aspirin treatment in patients with G6PD deficiency suggests hemolysis, which may influence stroke prognosis. The risk of hemoglobin decline should be carefully monitored in G6PD-deficient patients with ischemic stroke taking aspirin.
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http://dx.doi.org/10.1111/cns.13711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446213PMC
October 2021

Topological Alterations in White Matter Structural Networks in Blepharospasm.

Mov Disord 2021 Jul 28. Epub 2021 Jul 28.

Department of Neurology, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Background: Accumulating evidence indicates regional structural changes in the white matter (WM) of brains in patients with blepharospasm (BSP); however, whether large-scale WM structural networks undergo widespread reorganization in these patients remains unclear.

Objective: We investigated topology changes and global and local features of large-scale WM structural networks in BSP patients compared with hemifacial spasm (HFS) patients or healthy controls (HCs).

Methods: This cross-sectional study applied graph theoretical analysis to assess deterministic diffusion tensor tractography findings in 41 BSP patients, 41 HFS patients, and 41 HCs. WM structural connectivity in 246 cortical and subcortical regions was assessed, and topological parameters of the resulting graphs were calculated. Networks were compared among BSP, HFS, and HCs groups.

Results: Compared to HCs, both BSP and HFS patients showed alterations in network integration and segregation characterized by increased global efficiency and modularity and reduced shortest path length. Moreover, increased nodal efficiency in multiple cortical and subcortical regions was found in BSP and HFS patients compared with HCs. However, these differences were not found between BSP and HFS patients. Whereas all participants showed highly similar hub distribution patterns, BSP patients had additional hub regions not present in either HFS patients or HCs, which were located in the primary head and face motor cortex and basal ganglia.

Conclusions: Our findings suggest that the large-scale WM structural network undergoes an extensive reorganization in BSP, probably due to both dystonia-specific abnormalities and facial hyperkinetic movements. © 2021 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28736DOI Listing
July 2021

Impact of stroke center certification on rt-PA thrombolysis after acute ischemic stroke in South China from 2015 to 2020.

Int J Stroke 2021 Jul 20:17474930211031440. Epub 2021 Jul 20.

Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Background And Purpose: In China, stroke center certification was launched in 2015, but little is known about its impact on intravenous thrombolysis. This study aimed to evaluate the effects of stroke center certification on the use of intravenous thrombolysis during a five-year period in South China.

Methods: We retrospectively collected data regarding the use of recombinant tissue plasminogen activator (rt-PA) in 21 cities of Guangdong from 2015 to 2020. The annual thrombolysis rate was defined as the number of patients who underwent intravenous rt-PA therapy divided by the number of those who had acute ischemic stroke within the same year. The density of stroke centers was calculated as the number of stroke centers divided by the corresponding residents. Spearman's correlation analysis was used to determine the correlations between the annual thrombolysis rates and the number/density of stroke centers. Paired -test was used to compare differences in growth in annual thrombolysis rates before and after having stroke centers.

Results: From 2015 to 2020, the annual rt-PA thrombolysis rates of Guangdong increased from 1.4% to 7.2%, which was accompanied by an increase in the number of stroke centers from 0 to 82 and density of stroke centers from 0.00 to 0.71 per million population. The average annual rt-PA use in stroke centers was higher than that in non-stroke centers from 2016 to 2020 (all  < 0.05). There was a positive correlation of annual thrombolysis rates with the number of stroke centers ( = 1.00,  = 0.0028) and with the density of stroke centers in the 21 cities from 2018 to 2020 (all  < 0.05). The growth in annual thrombolysis rates significantly accelerated at the city-level after having stroke centers (1.55%/y vs. 0.77%/y,  < 0.001).

Conclusions: Stroke center certification may partially drive the increased use of rt-PA thrombolysis. Stroke center certification should be continually promoted to facilitate access to intravenous thrombolysis for patients with acute ischemic stroke.
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http://dx.doi.org/10.1177/17474930211031440DOI Listing
July 2021

Machine-learning method for localization of cerebral white matter hyperintensities in healthy adults based on retinal images.

Brain Commun 2021 Jul 3;3(3):fcab124. Epub 2021 Jun 3.

Margaret KL Cheung Research Centre for Management of Parkinsonism, Therese Pei Fong Chow Research Centre for Prevention of Dementia and Gerald Choa Neuroscience Centre, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China.

Retinal vessels are known to be associated with various cardiovascular and cerebrovascular disease outcomes. Recent research has shown significant correlations between retinal characteristics and the presence of cerebral small vessel disease as measured by white matter hyperintensities from cerebral magnetic resonance imaging. Early detection of age-related white matter changes using retinal images is potentially helpful for population screening and allow early behavioural and lifestyle intervention. This study investigates the ability of the machine-learning method for the localization of brain white matter hyperintensities. All subjects were age 65 or above without any history of stroke and dementia and recruited from local community centres and community networks. Subjects with known retinal disease or disease influencing vessel structure in colour retina images were excluded. All subjects received MRI on the brain, and age-related white matter changes grading was determined from MRI as the primary endpoint. The presence of age-related white matter changes on each of the six brain regions was also studied. Retinal images were captured using a fundus camera, and the analysis was done based on a machine-learning approach. A total of 240 subjects are included in the study. The analysis of various brain regions included the left and right sides of frontal lobes, parietal-occipital lobes and basal ganglia. Our results suggested that data from both eyes are essential for detecting age-related white matter changes in the brain regions, but the retinal parameters useful for estimation of the probability of age-related white matter changes in each of the brain regions may differ for different locations. Using a classification and regression tree approach, we also found that at least three significant heterogeneous subgroups of subjects were identified to be essential for the localization of age-related white matter changes. Namely those with age-related white matter changes in the right frontal lobe, those without age-related white matter changes in the right frontal lobe but with age-related white matter changes in the left parietal-occipital lobe, and the rest of the subjects. Outcomes such as risks of severe grading of age-related white matter changes and the proportion of hypertension were significantly related to these subgroups. Our study showed that automatic retinal image analysis is a convenient and non-invasive screening tool for detecting age-related white matter changes and cerebral small vessel disease with good overall performance. The localization analysis for various brain regions shows that the classification models on each of the six brain regions can be done, and it opens up potential future clinical application.
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http://dx.doi.org/10.1093/braincomms/fcab124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249101PMC
July 2021

Is Cerebral Amyloid-β Deposition Related to Post-stroke Cognitive Impairment?

Transl Stroke Res 2021 Dec 30;12(6):946-957. Epub 2021 Jun 30.

Department of Neurology, The First Affiliated Hospital, Sun Yat-Sen University; Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, No. 58 Zhongshan Road 2, Guangzhou, 510080, China.

Approximately two-thirds of ischemic stroke patients suffer from different levels of post-stroke cognitive impairment (PSCI), but the underlying mechanisms of PSCI remain unclear. Cerebral amyloid-β (Aβ) deposition, a pathological hallmark of Alzheimer's disease, has been discovered in the brains of stroke patients in some autopsy studies. However, less is known about the role of Aβ pathology in the development of PSCI. It is hypothesized that cerebral ischemic injury may lead to neurotoxic Aβ accumulation in the brain, which further induces secondary neurodegeneration and progressive cognitive decline after stroke onset. In this review, we summarized available evidence from pre-clinical and clinical studies relevant to the aforementioned hypothesis. We found inconsistency in the results obtained from studies in rodents, nonhuman primates, and stroke patients. Moreover, the causal relationship between post-stroke cerebral Aβ deposition and PSCI has been uncertain and controversial. Taken together, evidence supporting the hypothesis that brain ischemia induces cerebral Aβ deposition has been insufficient so far. And, there is still no consensus regarding the contribution of cerebral amyloid pathology to PSCI. Other non-amyloid neurodegenerative mechanisms might be involved and remain to be fully elucidated.
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http://dx.doi.org/10.1007/s12975-021-00921-5DOI Listing
December 2021

Machine Learning for Predicting Individual Severity of Blepharospasm Using Diffusion Tensor Imaging.

Front Neurosci 2021 13;15:670475. Epub 2021 May 13.

Department of Information, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

Accumulating diffusion tensor imaging (DTI) evidence suggests that white matter abnormalities evaluated by local diffusion homogeneity (LDH) or fractional anisotropy (FA) occur in patients with blepharospasm (BSP), both of which are significantly correlated with disease severity. However, whether the individual severity of BSP can be identified using these DTI metrics remains unknown. We aimed to investigate whether a combination of machine learning techniques and LDH or FA can accurately identify the individual severity of BSP. Forty-one patients with BSP were assessed using the Jankovic Rating Scale and DTI. The patients were assigned to non-functionally and functionally limited groups according to their Jankovic Rating Scale scores. A machine learning scheme consisting of beam search and support vector machines was designed to identify non-functionally versus functionally limited outcomes, with the input features being LDH or FA in 68 white matter regions. The proposed machine learning scheme with LDH or FA yielded an overall accuracy of 88.67 versus 85.19% in identifying non-functionally limited versus functionally limited outcomes. The scheme also identified a sensitivity of 91.40 versus 85.87% in correctly identifying functionally limited outcomes, a specificity of 83.33 versus 83.67% in accurately identifying non-functionally limited outcomes, and an area under the curve of 93.7 versus 91.3%. These findings suggest that a combination of LDH or FA measurements and a sophisticated machine learning scheme can accurately and reliably identify the individual disease severity in patients with BSP.
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http://dx.doi.org/10.3389/fnins.2021.670475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155629PMC
May 2021

Retraction Note: In-hospital cerebrovascular complications following orthotopic liver transplantation: A retrospective study.

BMC Neurol 2021 Apr 10;21(1):155. Epub 2021 Apr 10.

Department of Neurology and Stroke Centre, First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan Road 2, Guangzhou, 510080, PR China.

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http://dx.doi.org/10.1186/s12883-021-02175-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035757PMC
April 2021

Aspirin Therapy in Cardiovascular Disease with Glucose-6-Phosphate Dehydrogenase Deficiency, Safe or Not?

Am J Cardiovasc Drugs 2021 Jul 14;21(4):377-382. Epub 2020 Dec 14.

Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University; Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Southern China International Cooperation Base for Early Intervention and Functional Rehabilitation of Neurological Diseases, No. 58 Zhongshan Road 2, Guangzhou, 510080, China.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme defect, which may present as acute hemolysis, neonatal jaundice, or chronic hemolysis. Ingestion of fava beans, as well as infection and certain drugs, are the most typical causes of acute hemolysis in people with G6PD deficiency. Aspirin, the cornerstone in current therapies for the prevention of cardiovascular disease (CVD), is occasionally reported to induce acute hemolysis in G6PD-deficient individuals. G6PD deficiency is typically asymptomatic and many CVD patients with this enzyme defect start to take long-term aspirin therapy without G6PD activity examination; however, no consensus on the safety of aspirin in this population has been reached. A few studies have reported on this issue and produced contradictory results. In this review, we discuss the possible mechanisms of aspirin-induced hemolysis, and summarize clinical evidence regarding the safety of aspirin in subjects with G6PD deficiency.
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http://dx.doi.org/10.1007/s40256-020-00460-8DOI Listing
July 2021

Predisposing factors and radiological features in patients with internal carotid artery dissection or vertebral artery dissection.

BMC Neurol 2020 Dec 10;20(1):445. Epub 2020 Dec 10.

Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, No.58 Zhongshan Road 2, Guangzhou, 510080, China.

Background: Cervicocerebral artery dissection is an important cause of ischemic stroke in young and middle-aged individuals. However, very few studies have compared the differential features between internal carotid artery dissection (ICAD) and vertebral artery dissection (VAD), including both cervical and intracranial artery dissections. We conducted a study to investigate the predisposing factors and radiological features in patients with ICAD or VAD.

Methods: All cases diagnosed with cervicocerebral artery dissection, ICAD, or VAD were identified through a medical records database, between January 2010 and January 2020. Baseline characteristics, predisposing factors, and radiological features of ICAD versus VAD were compared.

Results: A total of 140 patients with cervicocerebral artery dissection were included in the study, including 84 patients in the ICAD group and 56 in the VAD group. The mean age of patients in the ICAD and VAD groups was 43.37 ± 14.01 and 41.00 ± 12.98 years old, respectively. Patients with ICAD were more likely to be men compared with VAD (85.71% vs. 67.86%, p = 0.012). The frequency of hypertension, diabetes, smoking, drinking, and cervical trauma did not differ between ICAD and VAD. Dissections of ICAD were more frequently at the extracranial portions of the artery compared with those of VAD (70.24% vs. 44.64%, p = 0.003). In contrast, dissections of VAD were more common in the intracranial artery (55.36% vs. 29.76%, p = 0.003). Radiologically, double lumen (36.90% vs. 19.64%, p = 0.029) and intimal flap (11.90% vs. 1.79%, p = 0.029) were more frequently observed in ICAD than in VAD, and dissecting aneurysms were less frequent (13.10% vs. 26.79%, p = 0.041).

Conclusions: The distributions of cervical and intracranial artery dissections were different between ICAD and VAD. The frequencies of radiological features detected in patients with ICAD and VAD also differed.
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http://dx.doi.org/10.1186/s12883-020-02020-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731460PMC
December 2020

Stent-Assisted Angioplasty in Spontaneous Bilateral Extracranial Internal Carotid Artery Dissection.

Front Neurol 2020 13;11:582253. Epub 2020 Nov 13.

Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Internal carotid artery dissection (ICAD) results from a tear in the intima or rupture of the vasa vasorum with bleeding within the media resulting in separation of the vessel wall layers and a false lumen. It may cause arterial stenosis, occlusion, or dissecting pseudoaneurysm. Currently, the treatment of ICAD is controversial, including drug therapy and endovascular stent implantation. Simultaneous spontaneous dissection of bilateral carotid artery is rarely reported. We reported a 39-year-old-man with bilateral ICAD. Although the long-term durability of endovascular stent remains to be determined, for ICAD failed with active drug treatment and combined with hemodynamic impairment, early endovascular stent should be considered.
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http://dx.doi.org/10.3389/fneur.2020.582253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691571PMC
November 2020

Structural Brain Changes in Blepharospasm: A Cortical Thickness and Diffusion Tensor Imaging Study.

Front Neurosci 2020 29;14:543802. Epub 2020 Oct 29.

Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China.

White matter abnormalities in blepharospasm (BSP) have been evaluated using conventional intra-voxel metrics, and changes in patterns of cortical thickness in BSP remain controversial. We aimed to determine whether local diffusion homogeneity, an inter-voxel diffusivity metric, could be valuable in detecting white matter abnormalities for BSP; whether these changes are related to disease features; and whether cortical thickness changes occur in BSP patients. Diffusion tensor and structural magnetic resonance imaging were collected for 29 patients with BSP and 30 healthy controls. Intergroup diffusion differences were compared using tract-based spatial statistics analysis and measures of cortical thickness were obtained. The relationship among cortical thickness, diffusion metric in significantly different regions, and behavioral measures were further assessed. There were no significant differences in cortical thickness and fractional anisotropy between the groups. Local diffusion homogeneity was higher in BSP patients than controls, primarily in the left superior longitudinal fasciculus, corpus callosum, left posterior corona radiata, and left posterior thalamic radiata ( 0.05, family-wise error corrected). The local diffusion homogeneity values in these regions were positively correlated with the Jankovic rating scale ( = 0.416, = 0.031) and BSP disability index ( = 0.453, = 0.018) in BSP patients. These results suggest that intra- and inter-voxel diffusive parameters are differentially sensitive to detecting BSP-related white matter abnormalities and that local diffusion homogeneity might be useful in assessing disability in BSP patients.
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http://dx.doi.org/10.3389/fnins.2020.543802DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658539PMC
October 2020

Regional High Wall Shear Stress Associated With Stenosis Regression in Symptomatic Intracranial Atherosclerotic Disease.

Stroke 2020 10 4;51(10):3064-3073. Epub 2020 Sep 4.

Shenzhen Research Institute, The Chinese University of Hong Kong, China (X.L.).

Background And Purpose: Understanding the mechanisms underlying progression/regression of symptomatic intracranial atherosclerotic stenosis (sICAS) will inform secondary prevention of the patients. Focal wall shear stress (WSS) may play an important role, which, however, had seldom been investigated.

Methods: Patients with acute ischemic stroke or transient ischemic attack (TIA) attributed to 50% to 99% intracranial atherosclerotic stenosis were recruited. All patients underwent cerebral computed tomography angiography at baseline, and a computational fluid dynamics model was built based on computed tomography angiography to simulate blood flow and quantify WSS in the vicinity of the sICAS lesion. All patients received optimal medical treatment and a second computed tomography angiography at 1 year. The change in the luminal stenosis from baseline to 1 year in sICAS was defined as progression (increased >10%), quiescence (±10%), or regression (decreased >10%). Associations between baseline WSS metrics and sICAS regression were analyzed.

Results: Among 39 patients (median age 62 years; 27 males), sICAS luminal stenosis progressed, remained quiescent and regressed in 6 (15.4%), 15 (38.5%), and 18 (46.2%) cases, respectively. A higher maximum WSS and larger high-WSS area, throughout the sICAS lesion or obtained separately in the proximal and distal parts of the lesion, were independently associated with regression of luminal stenosis in sICAS over 1 year.

Conclusions: A majority of sICAS lesions regress or stay quiescent in the luminal stenosis over 1 year after stroke under optimal medical treatment, when higher focal WSS may facilitate stenosis regression. Further studies of the effects of hemodynamics including WSS in altering plaque vulnerability and stroke risks are needed.
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http://dx.doi.org/10.1161/STROKEAHA.120.030615DOI Listing
October 2020

Safety and efficacy of low-dose aspirin in ischemic stroke patients with different G6PD conditions.

Int J Stroke 2021 06 2;16(4):411-419. Epub 2020 Sep 2.

Department of Neurology and Stroke Center, The First Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China.

Background And Purpose: Aspirin is the first recommended antiplatelet agent to prevention secondary stroke, but its safety and efficacy in stroke patients with glucose-6-phosphate dehydrogenase deficiency remain unclear. We sought to evaluate its safety and efficacy in ischemic stroke patients with and without glucose-6-phosphate dehydrogenase deficiency.

Methods: Patients with ischemic stroke receiving aspirin (100 mg/day) for three months were recruited for a multicenter, prospective, cohort study. Blood glucose-6-phosphate dehydrogenase activity was examined after stroke. Safety outcomes including acute hemolysis, moderate-to-severe bleeding, and death (vascular, all-cause), and efficacy outcome indicated as stroke recurrence were evaluated at three months. Risk factors associated with moderate-to-severe bleeding and all-cause death were determined using multivariate or Cox regression analysis.

Results: Among the included 1121 patients, 81 of 130 glucose-6-phosphate dehydrogenase deficient and 576 of 991 glucose-6-phosphate dehydrogenase normal patients received aspirin for three months. Acute hemolysis was observed in one of the glucose-6-phosphate dehydrogenase deficient and in none of the glucose-6-phosphate dehydrogenase normal patients ( = 0.876). The rates of moderate-to-severe bleeding were 2.5% and 0.3% ( = 0.045), and the percentages of all-cause death were 6.2% and 1.4% ( = 0.008) in the glucose-6-phosphate dehydrogenase deficient and glucose-6-phosphate dehydrogenase normal patients. Stroke recurrence rate was similar in the two groups (2.5% vs. 1.7%;  = 0.608). Glucose-6-phosphate dehydrogenase deficiency was significantly associated with increased risk of moderate-to-severe bleeding (adjust  = 0.048) and all-cause death during aspirin use (adjust  = 0.008).

Conclusions: Long-term low-dose aspirin therapy might relate to worse safety outcomes in patients with glucose-6-phosphate dehydrogenase deficiency and large clinical trials are needed to further confirm these findings.
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http://dx.doi.org/10.1177/1747493020950903DOI Listing
June 2021

Hypersensitivity of Vps33B mutant flies to non-pathogenic infections is dictated by aberrant activation of p38b MAP kinase.

Traffic 2020 09 3;21(9):578-589. Epub 2020 Aug 3.

Department of Neuroscience, UT Southwestern Medical Center, Dallas, Texas, USA.

Loss of the arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome-linked Vps33B protein results in exaggerated inflammatory responses upon activation of receptors of the innate immune system in both vertebrates and flies. However, little is known about the signaling elements downstream of these receptors that are critical for the hypersensitivity of Vps33B mutants. Here, we show that p38b MAP kinase contributes to the enhanced inflammatory responses in flies lacking Vps33B. Loss of p38b mitogen-activated protein kinase (MAPK) reduces enhanced inflammatory responses and prolongs the survival of infected Vps33B deficient flies. The function of p38 MAPK is not limited to its proinflammatory effects downstream of the PGRP-LC receptor as p38 also modulates endosomal trafficking of PGRP-LC and phagocytosis of bacteria. Expression of constitutively active p38b MAPK, but not dominant negative p38b MAPK enhances accumulation of endocytosed PGRP-LC receptors or phagocytosed bacteria within cells. Moreover, p38 MAPK is required for induction of macropinocytosis, an alternate pathway for the downregulation of immune receptors. Together, our data indicate that p38 MAPK activates multiple pathways that can contribute to the dysregulation of innate immune signaling in ARC syndrome.
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http://dx.doi.org/10.1111/tra.12756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682251PMC
September 2020

Glucose-6-phosphate dehydrogenase deficiency and stroke outcomes.

Neurology 2020 09 10;95(11):e1471-e1478. Epub 2020 Jul 10.

From Section II (S.X.), Department of Neurology (Z.O., Y.C., J.L., F.O., G.L., S.T., W.H., J.Z.), The First Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou; Department of Epidemiology and Biostatistics (X.G.), School of Public Health, Guangdong Pharmaceutical University; Department of Neurology and Stroke Center (Y.Z.), The First Affiliated Hospital of Jinan University, Guangzhou; Department of Neurology (Z.L.), The First Affiliated Hospital of Guangxi Medical University, Nanning; and Department of Neurology (W.D.), Meizhou Hospital Affiliated to Sun Yat-sen University, China.

Objective: To assess the risk of glucose-6-phosphate dehydrogenase (G6PD) on stroke prognosis, we compared outcomes between patients with stroke with and without G6PD deficiency.

Methods: The study recruited 1,251 patients with acute ischemic stroke. Patients were individually categorized into G6PD-deficiency and non-G6PD-deficiency groups according to G6PD activity upon admission. The primary endpoint was poor outcome at 3 months defined by a modified Rankin Scale (mRS) score ≥2 (including disability and death). Secondary outcomes included the overall mRS score at 3 months and in-hospital death and all death within 3 months. Logistic regression and Cox models, adjusted for potential confounders, were fitted to estimate the association of G6PD deficiency with the outcomes.

Results: Among 1,251 patients, 150 (12.0%) were G6PD-deficient. Patients with G6PD deficiency had higher proportions of large-artery atherosclerosis (odds ratio [OR] 1.53, 95% confidence interval [CI] 1.09-2.17) and stroke history (OR 1.93, 95% CI 1.26-2.90) compared to the non-G6PD-deficient group. The 2 groups differed significantly in the overall mRS score distribution (adjusted common OR 1.57, 95% CI 1.14-2.17). Patients with G6PD deficiency had higher rates of poor outcome at 3 months (adjusted OR 1.73, 95% CI 1.08-2.76; adjusted absolute risk increase 13.0%, 95% CI 2.4%-23.6%). The hazard ratio of in-hospital death for patients with G6PD-deficiency was 1.46 (95% CI 1.37-1.84).

Conclusions: G6PD deficiency is associated with the risk of poor outcome at 3 months after ischemic stroke and may increase the risk of in-hospital death. These findings suggest the rationality of G6PD screening in patients with stroke.
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http://dx.doi.org/10.1212/WNL.0000000000010245DOI Listing
September 2020

Klippel-Trenaunay and Sturge-Weber Overlap Syndrome with KRAS and GNAQ mutations.

Ann Clin Transl Neurol 2020 07 2;7(7):1258-1264. Epub 2020 Jul 2.

Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, No.58 Zhongshan Road 2, Guangzhou, 510080, China.

Patients with combined phenotypes of Sturge-Weber syndrome and Klippel-Trenaunay syndrome have been reported, though the underlying genetic spectrum in these individuals remains to be elucidated. We reported the patient presenting with Klippel-Trenaunay and Sturge-Weber overlap syndrome in mainland China. Histopathologic study confirmed the hemangioma of vein and capillary. Co-existence of a novel somatic KRAS c.182_183 delins TC mutation and GNAQ c.548G>A mutation was identified in the affected skin tissue rather than paired peripheral blood. The somatic mutations of GNAQ and KRAS may affect MAPK-ERK signaling pathway, resulting in endothelial anomaly and blood vessel malformation.
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http://dx.doi.org/10.1002/acn3.51106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359123PMC
July 2020

Chinese Stroke Association guidelines for clinical management of cerebrovascular disorders: executive summary and 2019 update of clinical management of cerebral venous sinus thrombosis.

Stroke Vasc Neurol 2020 06 13;5(2):152-158. Epub 2020 May 13.

Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University; Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China

Aim: Cerebral venous sinus thrombosis (CVST) is a less common cerebrovascular disease that predominantly affects young patients. The incidence of CVST is 2-5/10 000 000/year, accounting for 0.5%-1% of all stroke. To reduce mortality and morbidity associated with CVST, Chinese Stroke Association commissioned the authors to write the current guideline on the management of CVST.

Methods: PubMed (MEDLINE), CNKI and Wanfang database were searched for studies related to CVST from 1 January 1990 to 31 July 2019. Data were synthesised by evidence tables. Each recommendation was fully discussed by the writing group members and reviewed by Chinese Stroke Association Stroke Fellow Committees. Levels of evidence grading algorithm of Chinese Stroke Association was used to grade each recommendation.

Results: This guideline mainly focuses on the diagnostic evaluation, therapeutic strategies and secondary prevention of CVST. CT/CTV and MRI/MRV are recommended in the initial imaging evaluation of patients with suspected CVST. Anticoagulation therapy with low-molecular weight heparin should be initiated in patients with CVST immediately. After the acute stage, warfarin is recommended for 3-6 months to prevent the recurrence of CVST and other venous thromboembolic events.

Conclusions: The guideline summarises the current evidence regarding the management of CVST, and provides references for diagnosis, treatment and secondary prevention of CVST in China.
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http://dx.doi.org/10.1136/svn-2020-000358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337369PMC
June 2020

Mutations of are responsible for sporadic cerebral cavernous malformation and lead to a mulberry-like cluster in zebrafish.

J Cereb Blood Flow Metab 2021 06 4;41(6):1251-1263. Epub 2020 Apr 4.

Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China.

Although familial forms of cerebral cavernous malformation are mainly attributed to three genes (, and ), no mutation is identified in sporadic cerebral cavernous malformation cases with a unique lesion, indicating additional genes for sporadic cerebral cavernous malformation. To screen the candidate genes, we conducted whole exome sequencing in 31 sporadic cerebral cavernous malformation patients and 32 healthy controls, and identified 5 affected individuals carrying 6 heterozygous deleterious mutations in but no mutation in healthy individuals. To further confirm was associated with cerebral cavernous malformation, we generated homozygous knockout zebrafish and found mutation of in zebrafish led to a mulberry-like cluster of disordered-flow vascular channels which was reminiscent of human cerebral cavernous malformation. In addition, we revealed and were significantly downregulated due to mutation through transcriptomic sequencing and RT-qPCR analysis. Based on the mulberry-like phenotype partly rescued by mRNA of as well as , we suggested that promoted mulberry-like cluster via downregulation of and . Altogether, we firstly demonstrate is a novel candidate gene for sporadic cerebral cavernous malformation and the mutation of is responsible for the mulberry-like cluster in zebrafish.
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http://dx.doi.org/10.1177/0271678X20914996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142133PMC
June 2021

Blockade of Nogo-A/Nogo-66 receptor 1 (NgR1) Inhibits Autophagic Activation and Prevents Secondary Neuronal Damage in the Thalamus after Focal Cerebral Infarction in Hypertensive Rats.

Neuroscience 2020 04 14;431:103-114. Epub 2020 Feb 14.

Department of Neurology and Stroke Center, The First Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China. Electronic address:

Focal cerebral infarction leads to autophagic activation, which contributes to secondary neuronal damage in the ipsilateral thalamus. Although Nogo-A deactivation enhances neuronal plasticity, its role in autophagic activation in the thalamus after ischemic stroke remains unclear. This study aimed to investigate the potential roles of Nogo-A/Nogo-66 receptor 1 (NgR1) in autophagic activation in the ipsilateral thalamus after cerebral infarction. Focal neocortical infarction was established using the middle cerebral artery occlusion (MCAO) method. Secondary damage in the ipsilateral thalamus was assessed by Nissl staining and immunostaining. The expression of Nogo-A, NgR1, Rho-A and Rho-associated coiled-coil containing protein kinase 1 (ROCK1) as well as autophagic flux were evaluated by immunofluorescence and immunoblotting. The roles of Nogo-A-NgR1 signaling in autophagic activation were determined by intraventricular delivery of an NgR1 antagonist peptide, NEP1-40, at 24 h after MCAO. The results showed that Nogo-A and NgR1 overexpression temporally coincided with marked increases in the levels of Beclin1, LC3-II and sequestosome 1 (SQSTM1)/p62 in the ipsilateral thalamus at seven and fourteen days after MCAO. In contrast, NEP1-40 treatment significantly reduced the expression of Rho-A and ROCK1 which was accompanied by marked reductions of LC3-II conversion as well as the levels of Beclin1 and SQSTM1/p62. Furthermore, NEP1-40 treatment significantly reduced neuronal loss and gliosis in the ipsilateral thalamus, and accelerated somatosensory recovery at the observed time-points after MCAO. These results suggest that blockade of Nogo-A-NgR1 signaling inhibits autophagic activation, attenuates secondary neuronal damage in the ipsilateral thalamus, and promotes functional recovery after focal cerebral cortical infarction.
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http://dx.doi.org/10.1016/j.neuroscience.2020.02.010DOI Listing
April 2020

Derlin-1 exhibits oncogenic activities and indicates an unfavorable prognosis in breast cancer.

Cell Biol Int 2020 Feb 26;44(2):593-602. Epub 2019 Nov 26.

Department of Oncology, The Second Affiliated Hospital of Nanchang University, 330006, Jiangxi, China.

Derlin-1 is involved in the elimination of misfolded proteins and has been implicated in the progression of human cancers. However, its prognostic value and biological function in breast cancer remain unknown. Here, we show that Derlin-1 is overexpressed in breast cancer and exhibits oncogenic activities via interaction with UBE2C. Increased expression of Derlin-1 is correlated with lymph node metastasis, advanced clinical stage, and unfavorable overall survival in two cohorts containing over 1,000 patients. Multivariate analyses by the Cox regression model suggest Derlin-1 is an independent factor for poor prognosis. In vitro experiments demonstrate that Derlin-1 expression is transcriptionally upregulated by c-Myc. Ectopic expression of Derlin-1 promotes breast cancer cell proliferation and migration, whereas the knockdown of Derlin-1 results in the opposite phenotypes. Mechanistically, Derlin-1 directly binds to UBE2C to increase the phosphorylation of AKT and ERK. The treatment of UBE2C siRNA markedly attenuates Derlin-1-mediated cell growth and migration. Collectively, our data suggest Derlin-1 is a potential prognostic factor and functions as an oncogene in breast cancer.
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http://dx.doi.org/10.1002/cbin.11259DOI Listing
February 2020

Persistence of Gut Microbiota Dysbiosis and Chronic Systemic Inflammation After Cerebral Infarction in Cynomolgus Monkeys.

Front Neurol 2019 28;10:661. Epub 2019 Jun 28.

Department of Neurology and Stroke Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

The bidirectional interaction between the gut and brain after stroke through the immune-mediated pathway has been studied. However, the long-term effects of gut microbiota and systemic immune homeostasis after cerebral ischemia remain unclear. We examined long-term changes in the gut microbiota and systemic inflammatory cytokines after cerebral infarction in cynomolgus monkeys. Twelve monkeys underwent successful distal M1 segment of the left middle cerebral artery occlusion (MCAO) and were randomly and equally assigned to the MCAO-1.5 m, MCAO-6 m, and MCAO-12 m groups, which were sacrificed 1.5, 6, and 12 months after cerebral infarction induction, respectively. Four monkeys that underwent a sham operation were sacrificed 12 months later. The gut microbiota and short-chain fatty acids (SCFAs) were analyzed by 16S rDNA sequencing and gas chromatography mass spectrometry, respectively. Histological examinations of the transverse colon were performed. Plasma D-lactate, zonulin, lipopolysaccharide (LPS), tumor necrosis factor (TNF-α), interferon (IFN)-γ, and interleukin (IL)-6 were detected by immunoassay kits. The levels of the Bacteroidetes phylum and genus were significantly increased, while the Firmicutes phylum as well as the , and genera were decreased after cerebral infarction. Gut-originating SCFAs were significantly decreased 6 and 12 months after cerebral infarction ( < 0.05). We observed intestinal mucosal damage, evaluated by Chiu's score. Plasma D-lactate, zonulin, LPS, TNF-α, IFN-γ, and IL-6 were significantly increased after cerebral infarction ( < 0.05). Additionally, the increases in plasma LPS, TNF-α, IFN-γ, and IL-6 after cerebral infarction coincided with overgrowth of the Bacteroidetes phylum ( < 0.001). Cerebral infarction induces persistent host gut microbiota dysbiosis, intestinal mucosal damage, and chronic systemic inflammation in cynomolgus monkeys.
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http://dx.doi.org/10.3389/fneur.2019.00661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6611357PMC
June 2019

Neuronal loss without amyloid-β deposits in the thalamus and hippocampus in the late period after middle cerebral artery occlusion in cynomolgus monkeys.

Brain Pathol 2020 01 21;30(1):165-178. Epub 2019 Jul 21.

Department of Neurology and Stroke Center, National Key Clinical Department and Key Discipline of Neurology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Conflicting evidence exists regarding whether focal cerebral infarction contributes to cerebral amyloid-β (Aβ) deposition, as observed in Alzheimer's disease. In this study, we aimed to evaluate the presence of Aβ deposits in the ipsilateral thalamus and hippocampus 12 months post-stroke in non-human primates, whose brains are structurally and functionally similar to that of humans. Four young male cynomolgus monkeys were subjected to unilateral permanent middle cerebral artery occlusion (MCAO), and another four sham-operated monkeys served as controls. All monkeys underwent magnetic resonance imaging examination on post-operative day 7 to assess the location and size of the infarction. The numbers of neurons, astrocytes, microglia and the Aβ load in the non-affected thalamus and hippocampus ipsilaterally remote from infarct foci were examined immunohistochemically at sacrifice 12 months after operation. Thioflavin S and Congo Red stainings were used to identify amyloid deposits. Multiple Aβ antibodies recognizing both the N-terminal and C-terminal epitopes of Aβ peptides were used to avoid antibody cross-reactivity. Aβ levels in cerebrospinal fluid (CSF) and plasma were examined using enzyme-linked immunosorbent assay. The initial infarct was restricted to the left temporal, parietal, insular cortex and the subcortical white matter, while the thalamus and hippocampus remained intact. Of note, there were fewer neurons and more glia in the ipsilateral thalamus and hippocampus in the MCAO group at 12 months post-stroke compared to the control group (all P < 0.05). However, there was no sign of extracellular Aβ plaques in the thalamus or hippocampus. No statistically significant difference was found in CSF or plasma levels of Aβ , Aβ or the Aβ /Aβ ratio between the two groups (P > 0.05). These results suggest that significant secondary neuronal loss and reactive gliosis occur in the non-affected thalamus and hippocampus without Aβ deposits in the late period after MCAO in non-human primates.
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http://dx.doi.org/10.1111/bpa.12764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017993PMC
January 2020

A clinical research on the potential pathogenesis of somatic cancer related cerebral venous sinus thrombosis.

Medicine (Baltimore) 2019 May;98(19):e15134

Department of Neurology, The First Affiliated Hospital of Guangxi Medical University & Guangxi Key Laboratory Base of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-cerebrovascular Diseases, Nanning, 530021, Guangxi.

To investigate the pathogenesis of somatic solid cancer-related cerebral venous sinus thrombosis (CVST).A total of 174 patients with CVST were recruited from the hospital between January 2006 and December 2017 and divided into two groups: (1) somatic cancer-related CVST group, defined as active somatic solid cancer patients with acute CVST; (2) cancer group (CG), defined as active somatic solid cancer patients without CVST. The cancer group patients were age and gender-matched somatic cancer-related CVST group patients. In addition, the types and amount distribution of cancer in cancer group were also matched with somatic cancer-related CVST group patients.Compared to cancer group patients, somatic cancer-related CVST group patients had more intracranial metastasis, a higher platelet count, higher plasma D-dimer, carcinoembryonic antigen (CEA) and cancer antigen (CA) 125 levels, a greater platelet to lymphocyte ratio (PLR), and a greater platelet to neutrophil ratio (PNR). The risk for CVST in somatic cancer-related CVST group patients increased independently by 0.7% (odds ratio [OR] 1.007; 95% confidence interval [CI] 1.000, 1.015; P = .047) with a 1 ng/ml increase in D-dimer levels, by 4.6% (OR 1.046; 95% CI 1.011, 1.083; P = .010) with a 1 U/ml increase in CEA, by 2.7% (OR 1.027; 95% CI 1.003, 1.051; P = .025) with a 1 U/ml increase in CA125, and by 10.6% (OR 1.106; 95% CI 1.002, 1.220; P = .045) with a 1 unit increase in PNR.It was suggested that together impacts of elevated plasma D-dimer, CA125, CEA levels, and a greater PNR may lead to hypercoagulability and to trigger the development of cancer-related CVST.
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http://dx.doi.org/10.1097/MD.0000000000015134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6531122PMC
May 2019

Regional Shape Abnormalities in Thalamus and Verbal Memory Impairment After Subcortical Infarction.

Neurorehabil Neural Repair 2019 06 12;33(6):476-485. Epub 2019 May 12.

1 The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.

Subcortical infarcts can result in verbal memory impairment, but the potential underlying mechanisms remain unknown. We investigated the spatiotemporal deterioration patterns of brain structures in patients with subcortical infarction and identified the regions that contributed to verbal memory impairment. Cognitive assessment and structural magnetic resonance imaging were performed 1, 4, and 12 weeks after stroke onset in 28 left-hemisphere and 22 right-hemisphere stroke patients with subcortical infarction. Whole-brain volumetric analysis combined with a further-refined shape analysis was conducted to analyze longitudinal morphometric changes in brain structures and their relationship to verbal memory performance. Between weeks 1 and 12, significant volume decreases in the ipsilesional basal ganglia, inferior white matter, and thalamus were found in the left-hemisphere stroke group. Among those 3 structures, only the change rate of the thalamus volume was significantly correlated with that in immediate recall. For the right-hemisphere stroke group, only the ipsilesional basal ganglia survived the week 1 to week 12 group comparison, but its change rate was not significantly correlated with the verbal memory change rate. Shape analysis of the thalamus revealed atrophies of the ipsilesional thalamic subregions connected to the prefrontal, temporal, and premotor cortices in the left-hemisphere stroke group and positive correlations between the rates of those atrophies and the change rate in immediate recall. Secondary damage to the thalamus, especially to the left subregions connected to specific cortices, may be associated with early verbal memory impairment following an acute subcortical infarct.
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http://dx.doi.org/10.1177/1545968319846121DOI Listing
June 2019

Extracranial Artery Stenosis Is Associated With Total MRI Burden of Cerebral Small Vessel Disease in Ischemic Stroke Patients of Suspected Small or Large Artery Origins.

Front Neurol 2019 21;10:243. Epub 2019 Mar 21.

Department of Neurology and Stroke Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.

Extracranial artery stenosis (ECAS) is related to individual imaging markers of cerebral small vessel disease (cSVD). However, little has been reported on the association between ECAS and the total burden of cSVD as assessed by magnetic resonance imaging (MRI). The purpose of this study was to investigate the relationship between ECAS and cSVD burden in patients with ischemic stroke of suspected small or large artery origin. We reviewed consecutive patients with ischemic stroke of suspected small or large artery origin who underwent color Doppler ultrasonography and brain MRI. Bilateral extracranial cerebral arteries including common carotid artery, internal carotid artery (ICA), and proximal vertebral artery (VA, ostium, V2-3 segments) were assessed using color Doppler ultrasonography. ECAS severity was classified as no/mild stenosis, moderate stenosis, severe stenosis, or occlusion. The total cSVD score was assessed by awarding one point according to the load of each of these cSVD markers as determined using MRI; lacunar infarction, white matter hyperintensities, cerebral microbleeds, and enlarged perivascular spaces. The relationship between ECAS severity and cSVD burden according to MRI was examined. Two hundred and twenty one patients were included in this study (mean age 61 ± 12 years, 75.6% male). Hypertension, current smoking, hyperlipidaemia, and diabetic mellitus were frequent among the patients (67.4, 45.7, 43.9, and 36.7%, respectively), while the other vascular risk factors including previous stroke or TIA and alcohol excess were less frequent (19.0 and 15.4%, respectively). Patients with higher total cSVD burden was significantly older and had severer ECAS. The frequency of hypertension was significantly higher in patients with higher total cSVD burden. This analysis indicated that that increasing ECAS severity (from no stenosis through to 100%) was independently associated with increasing total cSVD score after adjusting for other vascular risk factors (odds ratio 1.76, 95% CI [1.16-2.69]). In this study, high levels of ECAS from ultrasound evidence were associated with coexisting advanced cerebral cSVD in ischemic stroke patients of suspected small or large artery origin. Further studies are required to determine if and how extracranial arterial imaging helps reduce cSVD burden or improves cognitive function.
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http://dx.doi.org/10.3389/fneur.2019.00243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437037PMC
March 2019

Retinal image analytics detects white matter hyperintensities in healthy adults.

Ann Clin Transl Neurol 2019 01 15;6(1):98-105. Epub 2018 Nov 15.

Clinical Trials and Biostatistics Lab CUHK Shenzhen Research Institute Shenzhen China.

Objective: We investigated whether an automatic retinal image analysis (ARIA) incorporating machine learning approach can identify asymptomatic older adults harboring high burden of white matter hyperintensities (WMH) using MRI as gold standard.

Methods: In this cross-sectional study, we evaluated 180 community-dwelling, stroke-, and dementia-free healthy subjects and performed ARIA by acquiring a nonmydriatic retinal fundus image. The primary outcome was the diagnostic performance of ARIA in detecting significant WMH on MRI brain, defined as age-related white matter changes (ARWMC) grade ≥2. We analyzed both clinical variables and retinal characteristics using logistic regression analysis. We developed a machine learning network model with ARIA to estimate WMH and its classification.

Results: All 180 subjects completed MRI and ARIA. The mean age was 70.3 ± 4.5 years, 70 (39%) were male. Risk factor profiles were: 106 (59%) hypertension, 31 (17%) diabetes, and 47 (26%) hyperlipidemia. Severe WMH (global ARWMC grade ≥2) was found in 56 (31%) subjects. The performance for detecting severe WMH with sensitivity (SN) 0.929 (95% CI from 0.819 to 0.977) and specificity (SP) 0.984 (95% CI from 0.937 to 0.997) was excellent. There was a good correlation between WMH volume (log-transformed) obtained from MRI versus those estimated from retinal images using ARIA with a correlation coefficient of 0.897 (95% CI from 0.864 to 0.922).

Interpretation: We developed a robust algorithm to automatically evaluate retinal fundus image that can identify subjects with high WMH burden. Further community-based prospective studies should be performed for early screening of population at risk of cerebral small vessel disease.
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http://dx.doi.org/10.1002/acn3.688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331948PMC
January 2019
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