The correlation between enlarged perivascular spaces and cognitive impairment in Parkinson's disease and vascular parkinsonism.

INTRODUCTION: The widespread use of brain magnetic resonance imaging (MRI) has revealed the correlation between enlarged perivascular spaces (EPVS) and cognitive impairment (CI). However, few studies have examined the correlation between MRI-visible EPVS and CI in patients with Parkinson's disease (PD) and vascular parkinsonism (VaP). This study explored how the number and main location of EPVS in PD and VaP are correlated with the occurrence of CI in these diseases to provide radiology markers and other evidence for early clinical diagnosis in a Chinese cohort. METHODS: Clinical data were prospectively collected from 77 patients: 26 patients clinically diagnosed with PD or probable PD, 19 patients clinically diagnosed with VaP, and 32 control subjects with normal cognitive function and no stroke or parkinsonism. The patients with PD and VaP were divided into a CI group and a no CI (NCI) group according to the Montreal Cognitive Assessment Beijing version (MoCA-BJ). The relevant clinical data were statistically analysed. RESULTS: The centrum semiovale (CSO)-EPVS, lacunes, Fazekas scores, global cortical atrophy scale (GCA) scores, Koedam posterior atrophy visual scale (KS) scores, and medial temporal atrophy (MTA) scores were higher in the PD-CI and VaP-CI groups than in the control group (adjusted P < 0.017). The number of basal ganglia (BG)-EPVS in the VaP group was higher than that in the PD and control groups (adjusted P < 0.017). BG-EPVS, Fazekas scores, GCA scores, KS scores, and MTA scores were higher in the VaP-CI group than in the PD-CI group (adjusted P < 0.017). Multivariate logistic regression analysis showed that the differences in BG-EPVS and Fazekas scores were not significant between PD-CI and VaP-CI patients (P > 0.05). CONCLUSION: VaP-CI results from multiple factors and is significantly associated with BG-EPVS, lacunes, white matter hyperintensities and brain atrophy. BG-EPVS can be used as an imaging marker to distinguish VaP-CI from PD-CI.

Noninvasive model for predicting future ischemic strokes in patients with silent lacunar infarction using radiomics.

BACKGROUND: This study aimed to investigate integrating radiomics with clinical factors in cranial computed tomography (CT) to predict ischemic strokes in patients with silent lacunar infarction (SLI). METHODS: Radiomic features were extracted from baseline cranial CT images of patients with SLI. A least absolute shrinkage and selection operator (LASSO)-Cox regression analysis was used to select significant prognostic factors based on ModelC with clinical factors, ModelR with radiomic features, and ModelCR with both factors. The Kaplan-Meier method was used to compare stroke-free survival probabilities. A nomogram and a calibration curve were used for further evaluation. RESULTS: Radiomic signature (p < 0.01), age (p = 0.09), dyslipidemia (p = 0.03), and multiple infarctions (p = 0.02) were independently associated with future ischemic strokes. ModelCR had the best accuracy with 6-, 12-, and 18-month areas under the curve of 0.84, 0.81, and 0.79 for the training cohort and 0.79, 0.88, and 0.75 for the validation cohort, respectively. Patients with a ModelCR score < 0.17 had higher probabilities of stroke-free survival. The prognostic nomogram and calibration curves of the training and validation cohorts showed acceptable discrimination and calibration capabilities (concordance index [95% confidence interval]: 0.7864 [0.70-0.86]; 0.7140 [0.59-0.83], respectively). CONCLUSIONS: Radiomic analysis based on baseline CT images may provide a novel approach for predicting future ischemic strokes in patients with SLI. Older patients and those with dyslipidemia or multiple infarctions are at higher risk for ischemic stroke and require close monitoring and intensive intervention.

Role of the score for the targeting of atrial fibrillation (STAF) combined with D-dimer in screening ischemic stroke patients with atrial fibrillation.

Background: We aim to explore the effect of the score for the targeting of atrial fibrillation (STAF) combined with the serum D-dimer (DD) level in screening acute ischemic stroke patients with atrial fibrillation (AF). Methods: This study is a retrospective case observation study. This study consecutively selected patients with acute ischemic stroke who were hospitalized in the Department of Neurology at Zhuhai Hospital Affiliated with Jinan University from February 2019 to February 2021. Venous blood was drawn from all patients within 24 hours of hospitalization for DD detection. In accordance with the medical records, the patients were classified into an AF group and a non-AF group and were scored according to the STAF standard. A combined test method was used to estimate the diagnostic screening value of the STAF combined with the DD value for acute ischemic stroke patients with AF.

Genomic characteristics of two strains of ESBL-producing Klebsiella pneumoniae ST268 isolated from different samples of one patient.

OBJECTIVES: This study reports the whole-genome sequences of two strains of extended-spectrum beta-lactamase (ESBL)-producing and multidrug-resistant (MDR) K. pneumoniae ST268 and explores their acquired antibiotic resistance genes (ARGs) and the mobile genetic elements (MGEs). METHODS: Two strains of K. pneumoniae ST268 were isolated from different samples of one patient. Assessment of antimicrobial susceptibility was performed, and then whole-genome sequencing was conducted. Acquired ARGs, insertion sequences, and transposons harboured by the two strains of K. pneumoniae ST268 were identified, and then the genetic contexts associated with the ARGs were analysed systematically. RESULTS: Two strains of K. pneumoniae ST268 were found to carry the 118.6-kb hybrid IncFIIK:IncQ1:repBR1701 plasmid. All the acquired ARGs carried by the IncF plasmid were found to be situated on the 25.3-kb MDR region bracketed by ISKpn19 and IS26, which was widely present in the plasmids in 14 STs of strains in K. pneumoniae but also in IncF plasmids from Shigella flexneri and Klebsiella quasipneumoniae. Notably, the IncF plasmids harbouring the 25.3-kb MDR region were geographically distributed mainly in China, and the pKP161637-1/pKP160802-1 in our study was the first report on the IncF plasmid carrying the 25.3-kb MDR region bracketed in K. pneumoniae ST268. CONCLUSIONS: Two strains of ESBL-producing K. pneumoniae ST268 with a MDR IncF plasmid were identified in a hospital in China. The ARGs were identified on the 25.3-kb MDR region, bracketed by ISKpn19 and IS26, of the IncF plasmids, which were present not only in the K. pneumoniae but also in the S. flexneri and K. quasipneumoniae.

VX-765 Alleviates ß-Amyloid Deposition and Secondary Degeneration in the Ipsilateral Hippocampus and Ameliorates Cognitive Decline after Focal Cortical Infarction in Rats.

Focal cortical infarction leads to secondary degeneration of the ipsilateral hippocampus, which is associated with poststroke cognitive impairment. VX-765 is a potent small-molecule caspase-1 inhibitor that protects against central nervous system diseases. The present study aimed to determine the protective effects of VX-765 on ß-amyloid (Aß) deposition and secondary degeneration in the hippocampus as well as cognitive decline after cortical infarction. Sprague-Dawley rats were used to establish a distal middle cerebral artery occlusion (dMCAO) model and randomly divided into the vehicle and VX-765 groups. Rats in the vehicle and VX-765 groups, respectively, were subcutaneously injected with VX-765 (50 mg/kg/d) and an isopycnic vehicle once a day for 28 days, starting 1 h after dMCAO. At the end of this 28-day period, cognitive impairment was evaluated with the Morris water maze, and secondary hippocampal damage was evaluated with Nissl staining and immunostaining methods. Neuronal damage and pyroptosis were detected by TUNEL and immunoblotting. The results revealed that VX-765 treatment ameliorated poststroke cognitive dysfunction after ischemia. VX-765 reduced Aß deposition, neuronal loss, and glial activation compared with the vehicle control. In addition, VX-765 treatment increased BDNF levels and normalized synaptophysin protein levels in the hippocampus after cortical infarction. Notably, VX-765 treatment significantly reduced the expression of the pyroptosis-related molecules caspase-1, NLRP3, apoptosis-associated speck-like protein (ASC), gasdermin D, IL-1ß, and IL-18. Additionally, VX-765 significantly decreased the numbers of TUNEL-positive cells and the levels of Bax and cleaved caspase-3 (cC3) and enhanced the levels of Bcl-2 and Bcl-xl after ischemia. Inflammatory pathways, such as the NF-κB and mitogen-activated protein kinase (MAPK) pathways, were inhibited by VX-765 treatment after ischemia. These findings revealed that VX-765 reduced Aß deposition, pyroptosis, and apoptosis in the ipsilateral hippocampus, which may be associated with reduced secondary degeneration and cognitive decline following focal cortical infarction.

The Correlation Among the Immunoglobulin G Synthesis Rate, IgG Index and Albumin Quotient in Guillain-Barré Syndrome and Chronic Inflammatory Demyelinating Polyradiculoneuropathy: A Retrospective Case-Control Study.

Background: The immunoglobulin G synthesis rate (IgG SR) and immunoglobulin G (IgG) index are indicators of abnormal intrathecal humoural immune responses, and the albumin quotient (QALB) is an indicator used to evaluate the completeness of the blood-cerebrospinal fluid barrier (BCB). No systematic reports regarding differences in Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are available. We assessed differences in the IgG SR, IgG index and QALB between GBS and CIDP patients in a Chinese cohort. Methods: A total of 234 patients were retrospectively enrolled in this study, and 167 clinically confirmed GBS and CIDP patients were selected. Meanwhile, 67 non-GBS and non-CIDP patients requiring cerebrospinal fluid (CSF) examination were enrolled as the control group. The IgG SR, IgG index and QALB were calculated using formulas. The relevant clinical data were subjected to statistical analysis. Results: Among the GBS and CIDP study groups and the control group, the QALB had the highest positive rate (80.00%) in the CIDP group (P < 0.01). The QALB stratification analysis showed that the ranges of 10 < QALB ≤ 30 were dominant in the GBS and CIDP groups, and the positive rate of CIDP was higher than that of GBS. Furthermore, a QALB ≤ 7 was dominant in the control group, and a QALB > 30 was dominant in the CIDP group. In receiver operating characteristic (ROC) curve analysis with the CIDP group as the trial group and the GBS group as the control group, the differences in the QALB were statistically significant (P < 0.01). To achieve a high specificity of 98~99%, the diagnostic cut-off value for the QALB was above 57.37 (sensitivity: 9.33%) or below 0.60 (sensitivity: 4.35%). Multivariate logistic regression analysis showed that the CIDP patients had a QALB higher than 57.37, and compared with that in the GBS patients, the difference in the QALB was statistically significant (P < 0.01). Conclusion: QALB elevation was associated with CIDP, while QALB values above 57.37 or below 0.60 had high specificity in differentiating between GBS and CIDP. In CIDP, the BCB is generally moderately to severely damaged; in GBS, the BCB is generally moderately damaged.

Combined therapy of intensive statin plus intravenous rt-PA in acute ischemic stroke: the INSPIRE randomized clinical trial.

OBJECTIVE: To investigate the safety and efficacy of intensive statin in the acute phase of ischemic stroke after intravenous thrombolysis therapy. METHODS: A total of 310 stroke patients treated with rt-PA were randomly scheduled into the intensive statin group (rosuvastatin 20 mg daily × 14 days) and the control group (rosuvastatin 5 mg daily × 14 days). The primary clinical endpoint was excellent functional outcome (mRS ≤ 1) at 3 months, and the primary safety endpoint was symptomatic intracranial hemorrhage (sICH) in 90 days. RESULTS: The intensive statin users did not achieve a favorable outcome in excellent functional outcome (mRS ≤ 1) at 3 months compared with controls (70.3% vs. 66.5%, p = 0.464). Intensive statin also not significantly improved the overall distribution of scores on the modified Rankin scale, as compared with controls (p = 0.82 by the Cochran-Mantel-Haenszel test). The incidence of primary safety endpoint events (sICH) in 90 days did not significantly differ between the intensive statin group and control group (0.6% vs. 1.3%, p > 0.999). CONCLUSION: The INSPIRE study indicated that intensive statin therapy may not improve clinical outcomes compared with the low dose of statin therapy in AIS patients undergoing intravenous thrombolysis, and the two groups had similar safety profile. CLINICAL TRIAL REGISTRATION: URL: http://www.chictr.org . Unique identifier: ChiCTR-IPR-16008642.

Differences in Thyroid Function and Autoantibodies in the Development of Guillain-Barré Syndrome vs. Chronic Inflammatory Demyelinating Polyradiculoneuropathy.

Background: Both Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are neurodegenerative and inflammatory demyelination disorders. Sporadic reports showed that the increased levels of thyroid function and autoantibodies are associated with GBS, CIDP, or both, but no systematic study has been reported. We assessed the differences of thyroid function and autoantibodies between GBS and CIDP in a Chinese cohort. Methods: A total of 256 patients were enrolled in this study. 175 clinically confirmed GBS and CIDP patients were selected. Meanwhile, 81 patients hospitalized for diseases other than GBS or CIDP with mild symptoms were enrolled as a control group. Relevant clinical data, including thyroid function, and autoantibody examinations, were collected for statistical analysis. Results: In the comparison of thyroid function and autoantibody parameters, the levels of total thyroxine (TT4), thyroid peroxidase antibody (TPO-Ab), and thyroglobulin antibody (TG-Ab) in the GBS group were all higher than those in the CIDP and Control groups (P < 0.01). The thyroid antibody positive rates in the GBS and CIDP groups were 70.10 and 14.10%, respectively (P < 0.01). In the receiver operating characteristic (ROC) curve analysis, TT4, TPO-Ab, and TG-Ab were higher in the GBS group and lower in the CIDP group (P < 0.01). To achieve a high specificity of 97-99%, the diagnostic cutoff value of TPO-Ab was higher than 133 IU/mL (Sensitivity: 11.34%) or lower than 0.01 IU/mL (Sensitivity: 9.09%), while the diagnostic cutoff value of TG-Ab was higher than 261.1 IU/mL (Sensitivity: 2.06%) or lower than 0.46 IU/mL (Sensitivity: 11.69%). Multivariate logistic regression analysis showed that the differences in TPO-Ab were statistically significant between GBS patients with TPO-Ab was higher than 133 IU/mL and CIDP patients (P < 0.01); the differences in TG-Ab were statistically significant between GBS patients with TG-Ab was higher than 261.1 IU/mL and CIDP patients (P < 0.05). Conclusion: The elevation of thyroid autoantibodies was associated with GBS. TPO-Ab higher than 133 IU/mL or lower than 0.01 IU/mL and TG-Ab higher than 261.1 IU/mL or lower than 0.46 IU/mL had high specificity for differentiating between GBS and CIDP; therefore, TPO-Ab and TG-Ab can be used as biomarkers for the differential diagnosis of GBS and CIDP.

Diagnostic value of STAF score in combination with D-dimer in cardioembolism.

The aim of this study was to evaluate the diagnostic value of the Score for the Targeting of Atrial Fibrillation (STAF) in combination with the serum D-dimer (DD) levels in cardioembolism(CE).This study was a retrospective case-onlystudy, consecutively including patients with acute ischemic stroke. All patients were evaluated following the STAF scoring criteria and were classified according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) etiology classification criteria. A total of 317 patients were enrolled, including 37 CE cases (11.67%). STAF ≥5 showed a sensitivity of 89% and a specificity of 91% for the diagnosis of CE, whereas DD >791.30 ng/mL had a sensitivity of 58% and a specificity of 78%. When the STAF was used in combination with the DD level, the sensitivity was 95%, and the specificity was 100%.STAF score is an excellent tool for the diagnosis of CE when combined with DD, and can facilitate the etiological classification of acute ischemic stroke.

Cognitive Function Characteristics of Parkinson's Disease with Sleep Disorders.

Objective. The aim of this study was to investigate the cognitive function characteristics of Parkinson's disease (PD) with sleep disorders. Methods. Consecutive patients with PD (n = 96), patients with primary sleep disorders (n = 76), and healthy control subjects (n = 66) were assessed. The patients with PD were classified into sleep disorder (PD-SD) and non-sleep disorder (PD-NSD) groups. Results. Among 96 patients with PD, 69 were diagnosed with a sleep disorder. There were 38 sleep disorder cases, 31 RBD cases, and 27 NSD cases. On the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and MoCA subtests, patients in the PD-SD, primary sleep disorder, and PD-NSD groups exhibited lower scores than those in the control group. Moreover, the PD-SD patients exhibited more significant cognitive impairment than was observed in the primary sleep disorder patients. In the PD-SD subgroup, the attention scores on the MoCA and on MoCA subtests were lower in the PD with RBD group than in the PD with insomnia group. Conclusion. PD with sleep disorders may exacerbate cognitive dysfunction in patients. PD associated with different types of sleep disorders differentially affects cognitive functions, and patients with PD with RBD exhibited poorer cognitive function than was seen in patients with PD with insomnia.

The role of hs-CRP, D-dimer and fibrinogen in differentiating etiological subtypes of ischemic stroke.

The aim of this study was to evaluate the diagnostic value of the serum biochemical markers high-sensitivity C-reactive protein (hs-CRP), D-dimer (DD) and fibrinogen (Fg) in differentiating etiological subtypes of ischemic stroke. This study was a retrospective case-only study, consecutively including patients with acute ischemic stroke. All patients were classified into subtypes using the TOAST classification system. A total of 317 patients were evaluated. Hs-CRP and DD levels were significantly different among the subtypes and were the highest in CE, followed by LAA and SAA; no significant difference between the subtypes was found for Fg. Hs-CRP > 6.96 mg/L was classified as the CE subtype, with a sensitivity of 41% and a specificity of 74%; DD > 791.30 ng/mL was classified as CE, with a sensitivity of 58% and a specificity of 78%. The combination of hs-CRP and DD classification as CE yielded a sensitivity of 65% and a specificity of 91%. DD > 791.30 ng/mL was considered an independent predictive factor of CE. Hs-CRP and DD could be useful for identifying the etiological subtypes of acute ischemic stroke, especially for predicting CE. The diagnostic value of DD was higher than that of hs-CRP.

The influence of UGT2B7 genotype on valproic acid pharmacokinetics in Chinese epilepsy patients.

PURPOSE: The aim of this study was to investigate the distribution and frequency of genetic polymorphisms in uridine diphosphate glucuronosyltransferase-2B7 (UGT2B7) in epilepsy patients and to evaluate the effect of these on the metabolism of valproic acid (VPA). METHODS: Single nucleotide polymorphisms in UGT2B7 were investigated in 102 epilepsy patients using DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism analysis. The steady-state plasma concentrations of VPA were determined in these patients, who had received VPA (approx. 500-1000 mg/day) for at least 2 weeks. RESULTS: Fourteen patients had the CC genotype at UGT2B7 C802T, 46 carried CT, and 42 carried the TT genotype. At UGT2B7 G211T, 78 patients had the GG genotype, 23 carried GT, and one individual had the TT genotype. The standardized trough plasma concentration of VPA was much lower in those patients with a T allele at UGT2B7 C802T than in those with the CC genotype (TT, 2.11 ± 1.26; CT, 2.31 ± 1.25; CC, 3.02 ± 1.32 µg kg mL(-1) mg(-1), p < 0.01). However, UGT2B7 G211T polymorphisms had no influence on the plasma concentration of VPA (GG, 2.28 ± 1.32, GT, 2.303 ± 1.38 µg kg mL(-1) mg(-1)). CONCLUSION: These results suggested that UGT2B7 C802T may be an important determinant of individual variability in the pharmacokinetics of VPA and that it may be necessary to increase the VPA dose for individuals with a T allele in order to achieve the therapeutic range of 50-100 µg/mL.