Abstract:Objective To characterize the features of patent foramen ovale(PFO)-related cryptogenic stroke using diffusion-weighted imaging(DWI)and to investigate the correlation between infarct size and cardiac CT characteristics of PFO.Methods A retrospective,consecutive cohort study was conducted on acute ischemic stroke patients admitted to Neurology Department of Xuanwu Hospital,Capital Medical University from January 2022 to September 2024.Patients were categorized into PFO group,arterio-arterial embolism(AAE)group,and atrial fibrillation(AF)group based on etiological diagnosis.Baseline clinical data,including age,height,body mass index,admission National Institutes of Health stroke scale(NIHSS)score,history of old cerebral infarction,hypertension,diabetes mellitus,coronary heart disease,dyslipidemia,and smoking history were collected and compared.All patients underwent head MR within 24 h of admission.DWI was used to analyze and compare infarct characteristics across the three groups,including lesion number(single or multiple),location(cortical+subcortical,deep white matter,cortical+subcortical+deep white matter,cerebellum+thalamus+brainstem),size(≥15 mm or＜15 mm,based on maximum transverse diameter;for multiple lesions,if any lesion had a maximum diameter≥15 mm,it was categorized as≥15 mm),infarcted vascular territory(anterior,posterior,or both circulations),and specific arterial supply(anterior cerebral artery,middle cerebral artery,posterior cerebral artery,basilar artery,posterior inferior cerebellar artery,superior cerebellar artery,anterior choroidal artery,or multiple arteries).Patients in the PFO group additionally underwent cardiac CT to measure PFO-related parameters:tunnel length,width,height,septum secundum thickness,and fossa ovalis length.Spearman correlation analysis was performed to evaluate the relationship between infarct size and PFO cardiac CT features.Results A total of 232 acute ischemic stroke patients were included(mean age[57±17]years,ranged 19-86 years;141 males,91 females),comprising 116 in the PFO group,36 in the AAE group,and 80 in the AF group.(1)The proportion of males in the PFO group was higher than that in the AF group,it was lower than that in the AAE group.The age,body mass index and proportions of patients with hypertension,diabetes,hyperlipidemia,coronary heart disease were all lower than those in the other two groups(both P＜0.016 7),while other baseline characteristics showed no significant differences(all P＞0.05).(2)The PFO group exhibited a higher proportion of multiple infarcts compared to the AAE group(83.62％[97/116]vs.61.11％[22/36],P＜0.016 7),but a lower proportion than the AF group(83.62％[97/116]vs.98.75％[79/80],P＜0.016 7).The PFO group also showed a significantly higher proportion of cortical+subcortical infarcts(47.41％[55/116]vs.11.11％[4/36]and 6.25％[5/80],respectively,both P＜0.016 7)and infarcts with a maximum diameter＜15 mm compared to both AAE and AF groups(66.38％[77/116]vs.36.11％[13/36]and 11.25％[9/80],respectively,both P＜0.016 7).Furthermore,the PFO group had a lower proportion of anterior circulation infarcts(27.59％[32/116]vs.69.44％[25/36]in AAE group and 67.50％[54/80]in AF group,both P＜0.016 7),but a higher proportion of posterior circulation infarcts(62.07％[72/116]vs.16.67％[6/36]in AAE group and 8.75％[7/80]in AF group,both P＜0.016 7).Specifically,middle cerebral artery infarcts were less common in the PFO group(18.97％[22/116]vs.66.67％[24/36]in AAE group and 52.50％[42/80]in AF group,both P＜0.016 7),while posterior cerebral artery infarcts were more common(48.28％[56/116]vs.8.33％[3/36]in AAE group and 8.75％[7/80]in AF group,both P＜0.016 7).(3)Spearman correlation analysis revealed that infarct size was negatively correlated with PFO tunnel length(rs=-0.429,P=0.029),fossa ovalis length(rs=-0.408,P=0.038),and septum secundum thickness(rs=-0.525,P=0.006),but not correlated with PFO width or height(both P＞0.05).Conclusions PFO-related cryptogenic stroke is predominantly characterized by multiple small infarcts,primarily located in the cortical+subcortical regions and posterior circulation.Infarct size was found to be negatively correlated with PFO tunnel length,fossa ovalis length,and septum secundum thickness.Comprehensive assessment integrating DWI and cardiac CT features may facilitate the identification of PFO-related stroke.These findings warrant further validation through larger,prospective studies.

Abstract:Sneddon syndrome is a rare neurocutaneous disorder that primarily affects small-and medium-sized arteries.Its clinical manifestations include livedo racemosa and recurrent cerebral ischemic events,and it may also involve multiple organs such as the heart,spleen,and kidneys.This disease can lead to early-onset stroke,making it a rare cause of stroke in young adults.This article reported a case of a young female patient who experienced two cerebral infarctions within one month.Genetic testing identified a homozygous mutation in the adenosine deaminase 2 gene,confirming the diagnosis of Sneddon syndrome.This case serves as a reference to improve clinical recognition of this disease.

Abstract:Objective To investigate the clinical and genetic characteristics of infantile early-onset Moyamoya disease associated with ring finger protein 213(RNF213)gene variants.Methods This study included retrospective,consecutive case series of infantile early-onset Moyamoya disease admitted to the Department of Pediatric Neurology,Wuhan Children's Hospital,Tongji Medical College,Huazhong University of Science and Technology,between June 2020 and June 2024.General and clinical data were collected,including sex,age,chief complaint,admission time,history of present illness,personal history,family history,neurological physical examination,auxiliary investigations,diagnosis/treatment course,and follow-up status.Genetic testing results of the patients and their parents were analyzed.Mutation sites were screened and annotated through bioinformatics analysis,and suspicious variants were validated by Sanger sequencing.The molecular evolutionary genetics analysis software MEGA(v11.0)was used for amino acid sequence alignment and conservation analysis of identified missense mutations.Based on the protein structure databases,the three-dimensional structure of the missense proteins was obtained through cryo-electron microscopy.The identified missense mutations were mapped onto this structure,and PyMOL(v2.0.6)was used for protein structure visualization and hydrogen bond analysis at variant sites.Results(1)Three infants with early-onset Moyamoya disease were enrolled(1 male,2 females).Initial symptoms included epileptic seizures,transient ischemic attacks,or acute cerebral infarction.Genetic testing revealed RNF213 missense mutations in all three patients:patient 1 carried p.Arg4810Lys and p.Thr1727Met(both maternally inherited);patient 2 carried p.Arg4810Lys(paternally inherited);patient 3 carried a de novo p.Lys4136Gln mutation(both parents were wild-type).All patients underwent indirect cerebral revascularization.Postoperatively,epileptic seizures and cerebral ischemic events gradually resolved,the modified Rankin scale scores at the last follow-up were 2,1,and 2,respectively.(2)The amino acid residues threonine 1727(THR1727),lysine 4136(LYS4136),and arginine 4810(ARG4810)in the RNF213 protein were absolutely conserved across all three patients.Compared to wild-type ARG4810,the p.Arg4810Lys mutation occurred within an α-helix and reduced internal hydrogen bond interactions by one.The p.Thr1727Met mutation reduced hydrogen bonding by one compared to wild-type THR1727.The p.Lys4136Gln mutation reduced hydrogen bonding by one relative to wild-type LYS4136 and altered residues connecting two α-helices.Conclusions Infantile early-onset Moyamoya disease has insidious onset,severe progression,and diverse clinical manifestations,making it prone to misdiagnosis.RNF213 gene p.Arg4810Lys,p.Thr1727Met and p.Lys4136Gln mutations contribute to the pathogenesis of Moyamoya disease by affecting molecular mechanisms underlying its protein function.Early genetic testing for RNF213 variants aids clinical diagnosis.Indirect cerebral revascularization may benefit the affected infants.These findings require further validation through large-scale,prospective,multicenter studies.

Abstract:Objective To investigate cortical morphological changes and structural covariance network(SCN)topological features in patients with visuospatial neglect(VSN)after stroke.Methods A retrospective analysis was conducted on acute stroke patients admitted consecutively to the Department of Rehabilitation Medicine,Xuanwu Hospital,Capital Medical University,from December 2023 to February 2025.General and clinical data were collected and compared,including age,sex,stroke type(hemorrhagic or ischemic),and time from stroke onset to first brain MRI.All patients were assessed for VSN using the line bisection task,line cancellation test,and star cancellation test.Patients with VSN were assigned to the VSN group,and those without VSN to the non-VSN group.Brain MRI was used to collect patients' brain structural images.T1-weighted MRI data were processed using Freesurfer for whole-brain segmentation.Based on the Desikan-Killiany atlas,the cortex was parcellated into 68 regions per hemisphere,total intracranial volume and cortical parameters were extracted,including cortical area(CA),mean cortical curvature(CC),cortical thickness(CT),and cortical volume(CV).A region-specific asymmetry index(AI)was calculated for cortical parameters of each brain regions using(left-right)/(left+right)to assess cortical lateralization.Analyze the SCN of each cortical parameters through covariance matrix to reflect covariation pattern of each brain region's structural morphological alternations.SCN were constructed separately for each cortical parameter based on inter-regional Pearson correlation coefficients(absolute values),with intracranial volume,age,and sex controlled via linear regression.The resulting 68×68 SCN matrices were transformed into binary networks across a sparsity range of 0.1 to 0.4(in 0.01 steps),and graph theoretical analysis were performed.Permutation tests were used to compare the global and local graph theoretical metrics of cortical SCN under each cortical parameters with different sparsity.Global metrics included clustering coefficient,path length,small-worldness parameters(normalized clustering coefficient[Gamma],normalized path length[Lambda],and small-world index[Sigma]),global efficiency,and average local efficiency.Local metrics included nodal degree,betweenness centrality,and nodal efficiency.Results(1)A total of 109 acute stroke patients were included(81 males,28 females,aged 30-80 years,mean[64±9]years),with 54 in the VSN group and 55 in the non-VSN group.No significant differences were found in age,sex,stroke type,or time from stroke onset to MRI between two groups(all P＞0.05).(2)Comparison of cortical features(of different brain regions)between two groups showed significantly larger CA in the right insular surface area in the VSN group(2 466.50[2 143.75,2 662.50]mm2 vs.2 128.00[1 961.00,2 479.00)]mm2,P=0.037).No significant differences were observed in other regions or metrics(all P＞0.05).The VSN group has significantly lower AI values for CT in the right isthmus cingulate gyrus(-0.01[-0.05,0.03]vs.0.02[-0.01,0.06],P=0.028)and postcentral gyrus(-0.02[-0.04,0.00]vs.0.00[-0.02,0.02],P=0.026).No significant AI differences were observed in other regions or metrics(all P＞0.05).(3)For global network metrics:in the CA-based VSN,compared with the non-VSN group,Sigma values were significantly higher in the VSN group across multiple sparsity thresholds and at the average sparsity level(P＜0.01).In the CT-based SCN,Lambda values were significantly higher in the VSN group at most sparsity thresholds and at the average level(P=0.004).In the CC-based SCN,clustering coefficient and average local efficiency were significantly lower in the VSN group across most sparsity thresholds and average sparsity(P＜0.01).No significant differences were found in global metrics within the CV-based SCN.(4)For local metrics:in the CV-based SCN,compared with the non-VSN group,the VSN group showed significantly lower nodal efficiency in the left inferior temporal gyrus at most sparsity thresholds and at the average level(0.35[0.29,0.50]vs.0.65[0.51,0.72],P＜0.01).No significant differences in local metrics were observed in other SCN between the two groups.Conclusions Patients with VSN exhibit abnormal cortical morphology and SCN topology,characterized by reduced overall integration efficiency and weakened local connectivity,alongside enhanced small-worldness and possible compensatory reorganization.The conclusions of this study require further validation in multicenter,large-scale,prospective studies.

Abstract:Objective To investigate the correlation between enlarged perivascular spaces(EPVS)in different regions and glymphatic system(GS)function with cognitive function in patients with recent subcortical small infarction(RSSI).Methods A retrospective study was conducted by consecutively enrolling patients with RSSI who were hospitalized in the Department of Neurology at the Third Affiliated Hospital of Nanjing Medical University(Changzhou Second People's Hospital)from December 2023 to December 2024.Baseline and clinical data were collected,including age,sex,body mass index(BMI),history of smoking and alcohol consumption,hypertension,diabetes mellitus,atrial fibrillation,coronary heart disease,and laboratory indicators(including homocysteine,total cholesterol,triglycerides,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,glycated hemoglobin,uric acid,and creatinine).Cognitive function was assessed within 7 d of onset using the mini-mental state examination(MMSE)and Montreal cognitive assessment(MoCA)scale,which covers seven cognitive domains:visuospatial and executive functioning,naming,attention,language,abstraction,memory,and orientation.All patients underwent brain MRI within 3 d of admission,including diffusion tensor imaging(DTI)sequences.The DTI along the perivascular space(DTI-ALPS)post-processing tool was used to calculate the DTI-ALPS index on both sides,and the mean value was taken as an indicator to evaluate overall GS function.The volumes of EPVS in the basal ganglia(BG)and centrum semiovale(CSO)were measured.EPVS severity was visually rated based on Potter's method(on a scale range from 0 to 4)and categorized into a none-to-mild(grades 0-1)and a moderate-to-severe(grades 2-4)group.Patients were further classified by region into a BG-EPVS and a CSO-EPVS subgroups under each severity group.(1)Univariate analyses were performed to compare baseline characteristics,DTI-ALPS index,and cognitive assessment scores between groups.Variables with P＜0.05 in univariate analyses were tested for multicollinearity using variance inflation factor.Variables without multicollinearity were included in multivariate Logistic regression to identify independent factors associated with BG-EPVS.To assess the robustness of the predictive value of the DTI-ALPS index,outlier diagnostics and exclusion were performed,followed by re-estimation of the Logistic regression model.Spearman's correlation analysis was used to examine the associations of BG-EPVS volume with the DTI-ALPS index,MMSE scale score,MoCA scale score,and each cognitive domain score.Mediation analysis was conducted to evaluate whether the DTI-ALPS index mediated the relationship between BG-EPVS volume and MoCA scale score.Results A total of 65 RSSI patients were included in the study,comprising 34 males and 3 1 females,aged 37 to 78 years,with a mean age of(53±15)years.Among them,30 patients were classified into the none-to-mild EPVS group and 35 into the moderate-to-severe EPVS group.For regional classification,34 were in the none-to-mild BG-EPVS group and 31 in the moderate-to-severe BG-EPVS group;36 were in the none-to-mild CSO-EPVS group and 29 in the moderate-to-severe CSO-EPVS group.(1)Univariate analysis showed,in both overall EPVS and BG-EPVS subgroup,the none-to-mild groups had lower age,lower proportions of male and hypertensive patients,and higher DTI-ALPS indices,MMSE scale scores,and MoCA scale scores than the moderate-to-severe groups(all P＜0.05).No significant differences were found in other baseline or clinical characteristics(all P＞0.05).In the CSO-EPVS subgroup,age was the only variable differed significantly between the none-to-mild group(significantly younger)and the moderate-to-severe group(P＜0.05),no other variables showed significant differences between the groups(all P＞0.05).(2)No multicollinearity was found among age,sex,hypertension,and the DTI-ALPS index through the multicollinearity analysis.Multivariate Logistic regression identified older age(OR,4.410,95％CI 1.211-16.025,P=0.024),male(OR,1.076,95％CI 1.001-1.156,P=0.048),and hypertension(OR,6.287,95％CI 1.635-24.167,P=0.007)as independent risk factors for moderate-to-severe BG-EPVS in RSSI patients,while a higher DTI-ALPS index was an independent protective factor(OR,0.002,95％CI 0.000-0.904,P=0.046).To assess the robustness of this model,six outlier cases were identified and excluded.After reanalysis,the negative association between the DTI-ALPS index and BG-EPVS risk remained significant(OR,0.050,95％CI 0.003-0.974,P=0.048).(3)Spearman correlation analysis revealed that the BG-EPVS volume in RSSI patients was negatively correlated with the DTI-ALPS index(rs=-0.842,P=0.007),MMSE scale score(rs=-0.491,P=0.033),MoCA scale score(rs=-0.563,P=0.018),and visuospatial/executive function score(rs=-0.596,P=0.001).No significant correlations were found between BG-EPVS volume and other cognitive domains,including naming,attention,language,abstraction,memory,and orientation(all P＞0.05).(4)Mediation analysis showed that the total effect size of BG-EPVS volume on MoCA scale score was-0.673,with a direct effect size of-0.537(account for 79.79％of the total effect size)and an indirect effect size via the DTI-ALPS index of-0.136(account for 20.21％).Conclusions In RSSI patients,age,sex,hypertension,and the DTI-ALPS index were identified as independent factors associated with the severity of BG-EPVS.BG-EPVS volume was negatively correlated with the DTI-ALPS index and cognitive function scores in RSSI patients.Moreover,the DTI-ALPS index mediated the relationship between BG-EPVS volume and cognitive function in RSSI patients.

Abstract:Due to aging of society,acceleration of urbanization and ubiquity of unhealthy lifestyles,the burden of stroke disease in China has witnessed a rapid escalation.Under the auspices of the National Health Commission,the prevention and treatment of stroke in China have received vigorous support from health authorities at all levels across the country,along with the proactive participation of disease prevention and management agencies,medical and health institutions,and the majority of medical staff,and achievied remarkable outcomes.The construction of stroke centers in China is administratively-driven.From 2021 to 2022,under the organization and promotion of health administration departments at all levels,the integration of resources,optimization of processes and collaboration among disciplines in medical institutions have been implemented,efficient treatment green channels have been established,standardized diagnosis and treatment services have been provided,and a"patient-centered"diagnosis and treatment model for specific stroke diseases has been established.The five-in-one stroke prevention and control system with Chinese characteristics has been initially accomplished,which encompasses"prevention,treatment,management,health and wellness".This summary provided the epidemiology of stroke,the advancement of stroke center construction,the evolution of appropriate technologies in stroke centers and the analysis of related indicators,and recapitulates the progress of stroke center work in 2022 and the outlook of future endeavors.