Higher fibrinogen and neutrophil-to-lymphocyte ratio are associated with the early poor response to intravenous thrombolysis in acute ischemic stroke.

Background: Inflammation and platelet activation play pivotal roles in acute ischemic stroke (AIS) pathogenesis. Early response to thrombolysis is a vital indicator for the long-term prognosis of AIS. However, the correlation between fibrinogen or the neutrophil-to-lymphocyte ratio (NLR) and the early response to intravenous thrombolysis in patients with AIS remains unclear. Methods: AIS patients undergoing intravenous thrombolysis were enrolled between January 2018 and May 2023. Blood cell counts were sampled before thrombolysis. A good response was defined as a National Institutes of Health Stroke Scale (NIHSS) score decreased ≥4 or complete recovery 24 h after thrombolysis treatment. A poor response was defined as any increase in the NIHSS score or a decrease in the NIHSS score <4 at the 24 h after thrombolysis treatment compared with that at admission. Logistic regression analysis was performed to explore the relationship of the fibrinogen level and NLR with a poor thrombolysis response. Receiver operating characteristic (ROC) analysis was used to assess the ability of the fibrinogen level and NLR to discriminate poor responders. Results: Among 700 recruited patients, 268 (38.29%) were diagnosed with a good response, and 432 (61.71%) were diagnosed with a poor response to intravenous thrombolysis. A binary logistic regression model indicated that an elevated fibrinogen level (odds ratio [OR], 1.693; 95% confidence interval [CI] 1.325-2.122, P < 0.001) and NLR (OR, 1.253; 95% CI, 1.210-2.005, P = 0.001) were independent factors for a poor response. The area under the curve (AUC) values for the fibrinogen level, NLR and fibrinogen level combined with the NLR for a poor response were 0.708, 0.605, and 0.728, respectively. Conclusions: Our research indicates that the levels of fibrinogen and NLR at admission can be used as a prognostic factor to predict early poor response to intravenous thrombolysis.

Study on the Clinical Features of Parkinson's Disease With Probable Rapid Eye Movement Sleep Behavior Disorder.

Objective: To investigate the clinical features and factors associated with Parkinson's disease (PD) patients with probable rapid eye movement sleep behavior disorder (PD-pRBD). Methods: A total of 2,440 patients with clinically established or clinically probable PD were divided into two groups: PD-pRBD and PD without pRBD (PD-NRBD), according to the RBD questionnaire-Hong Kong. Data collection included demographic data, basic clinical history, and motor and non-motor symptoms. Based on the onset time of pRBD and the motor symptoms in PD, PD-pRBD patients were further divided into the pRBD prior to PD (PD-prRBD) group and the pRBD posterior to PD (PD-poRBD) group. Clinical features were compared between the PD-pRBD and PD-NRBD groups, as well as the PD-prRBD and PD-poRBD groups. The associated factors of pRBD were also explored. Results: The prevalence of pRBD was 41.4% (1,010 out of the total of 2,440) in our PD cohort. Further, compared with the PD-NRBD group, the PD-pRBD group had longer disease duration and more severe motor symptoms. Moreover, the PD-pRBD group had significantly higher levodopa equivalent daily dose and a higher ratio of dyskinesia, wearing-off, and offset of the Hoehn-Yahr stage. The scores on the non-motor symptom rating scale (NMSS), cognitive impairment, Parkinson's disease sleep scale (PDSS), excessive daytime sleepiness, constipation, hyposmia, depression, and the 39-item Parkinson's disease questionnaire also appeared worse in the PD-pRBD group. Significant differences in the educational level, disease duration, disease progression, Unified Parkinson's Disease Rating Scale (UPDRS)-II, UPDRS-III, tremor, rigidity, bradykinesia, posture gait, frozen gait, levodopa equivalent daily dose, dyskinesia, wearing-off, Hoehn-Yahr stage, NMSS-6, PDSS, and communication score widely existed between the PD-prRBD and PD-poRBD groups. Late-onset PD, long disease duration, high UPDRS-I score, high NMSS-4 score, low PDSS score, constipation, and hyposmia were all identified as the risk factors for PD-pRBD. Conclusions: Compared with the PD-NRBD group, the PD-pRBD group may have more severe motor symptoms, motor complications, and non-motor symptoms as well as a substandard quality of life. Further, late-onset PD, long disease duration, high UPDRS-I score, high NMSS-4 score, low PDSS score, constipation, and hyposmia can be risk factors for RBD in PD. Differences also occurred between the PD-prRBD and PD-poRBD groups.

Alzheimer's disease susceptibility genes modify the risk of Parkinson disease and Parkinson's disease-associated cognitive impairment.

The pathogenic mechanism underlying Parkinson's disease (PD) and PD- Cognitive impairment (CI) remains elusive. Its potential link to the risk factors in Alzheimer's disease (AD) is unclear. In this study, we analyzed 16 CE-associated single nucleotide polymorphisms (SNPs) in twelve genes in a Chinese cohort of 450 PD cases and 449 controls. Among our 298 cases clinically evaluated for CI, 113 cases did not show CI signs (PD-NC), 86 cases had mildly cognitive impairment (PD-MCI) and 99 cases had dementia (PD-D). We found that the APOE ε4 allele is associated with a higher risk for PD-D. Gene-gene interaction analysis revealed that three significant gene-gene interactions, including BDNF and CLU, APOE and CR1, and DYRK1A and CD2AP increase the risk for PD. Because these SNPs are known genetic risk factors for AD, their contribution to PD and PD-D shown in this study suggests that PD/PD-D and AD may share convergent pathways in their pathogenesis through gene-gene interactions.

Altered Functional Brain Connectomes between Sporadic and Familial Parkinson's Patients.

Familial Parkinson's disease (PD) is often caused by mutation of a certain gene, while sporadic PD is associated with variants of genes which can influence the susceptibility to PD. The goal of this study was to investigate the difference between the two forms of PD in terms of brain abnormalities using resting-state functional MRI and graph theory. Thirty-one familial PD patients and 36 sporadic PD patients underwent resting-state functional MRI scanning. Frequency-dependent functional connectivity was calculated for each subject using wavelet-based correlations of BOLD signal over 246 brain regions from Brainnetome Atlas. Graph theoretical analysis was then performed to analyze the topology of the functional network, and functional connectome differences were identified with a network-based statistical approach. Our results revealed a frequency-specific (0.016 and 0.031 Hz) connectome difference between familial and sporadic forms of PD, as indicated by an increase in assortativity and decrease in the nodal strength in the left medial amygdala of the familial PD group. In addition, the familial PD patients also showed a distinctive functional network between the left medial amygdala and regions related to retrieval of motion information. The present study indicates that the medial amygdala might be most vulnerable to both sporadic and familial PD. Our findings provide some new insights into disrupted resting-state functional connectomes between sporadic PD and familial PD.

Identifying the presence of Parkinson's disease using low-frequency fluctuations in BOLD signals.

Parkinson's disease (PD) is a chronic, progressive, and degenerative neurological disorder that is characterized by the degeneration of dopamine neurons in the substantia nigra and the formation of intracellular Lewy inclusion bodies. Resting-state functional magnetic resonance imaging (RS-fMRI) has demonstrated evidence of changes in metabolic patterns in individuals with PD. The purpose of this study was to determine whether the presence of PD could be "predicted" based on resting fluctuations in the blood oxygenation level dependent signal. We utilized RS-fMRI to measure the amplitude of low-frequency fluctuation (ALFF) and the fractional ALFF (fALFF) in 51 patients with PD and 50 age- and sex-matched healthy controls. Compared with the healthy controls, the individuals with PD exhibited altered ALFFs in the bilateral lingual gyrus and left putamen and an altered fALFF in the right cerebellum posterior lobe. Support vector machines (SVMs), which comprise a supervised pattern recognition method that enables predictions at the individual level, were trained to separate individuals with PD from healthy controls based on the ALFF and fALFF. Using the leave-one-out cross-validation method to analyze our sample, we reliably distinguished the participants with PD from the controls with 92% sensitivity and 87% specificity. Overall, these findings suggest that the SVM-neuroimaging approach may be of particular clinical value because it enables the accurate identification of PD at the individual level. RS-fMRI should be considered for development as a biomarker and an analytical tool for the evaluation of PD.

RAB39B gene mutations are not linked to familial Parkinson's disease in China.

Recently, RAB39B mutations were reported to be a causative factor in patients with Parkinson's disease (PD). To validate the role of RAB39B in familial PD, a total of 195 subjects consisting of 108 PD families with autosomal-dominant (AD) inheritance and 87 PD families with autosomal-recessive (AR) inheritance in the Chinese Han population from mainland China were included in this study. We did not identify any variants in the coding region or the exon-intron boundaries of the gene by Sanger sequencing method in the DNA samples of 180 patients (100 with AD and 80 with AR). Furthermore, we did not find any variants in the RAB39B gene when Whole-exome sequencing (WES) was applied to DNA samples from 15 patients (8 with AD and 7 with AR) for further genetic analysis. Additionally, when quantitative real-time PCR was used to exclude large rearrangement variants in these patients, we found no dosage mutations in RAB39B gene. Our results suggest that RAB39B mutation is very rare in familial PD and may not be a major cause of familial PD in the Chinese Han Population.