Neurological Sciences最新文献

Neurodegenerative disorders like Parkinson's disease (PD) are defined by the gradual degeneration of neurons across various regions of the central nervous system, which ultimately leads to brain dysfunction in the affected patients. The utilization of stem cell-based approaches, encompassing fetal ventral mesencephalic cells, human embryonic stem cells (hESCs), and human induced pluripotent stem cells (hiPSCs), holds great promise for PD patients. The modeling of neurodegenerative diseases using stem cells provides a valuable platform to screen potential therapeutic agents and investigate disease mechanisms. However, the common clinical use of stem cell therapies is hindered by related ethical concerns, the risk of immunological rejection, and the lack of established grafting protocols. The conversion of differentiated adult cells into induced pluripotent stem cells (iPSCs) has sparked renewed optimism for the progress of cell-based replacement therapeutic approaches. This review highlights the recent progress in the application of stem cell technologies, specifically the utilization of hiPSCs, for the treatment of PD. Additionally, the review discusses the potential of hiPSCs in PD, which can facilitate the translation of iPSC-based approaches into clinical settings for PD treatment.

Background: Data regarding management of patients already on an antiplatelet when presenting with an ischaemic stroke or transient ischaemic attack (TIA) are limited. This secondary analysis of the triple antiplatelets for reducing dependency in ischaemic stroke (TARDIS) trial explored clinical outcomes across prior antiplatelet groups.

Methods: TARDIS was an international prospective-randomised open-label blinded-endpoint trial assessing 30 days of triple vs. guideline antiplatelet therapy in patients with acute ischaemic stroke or TIA. The number of pre-stroke/TIA antiplatelet agents was collected pre-randomisation. The primary outcome was the combined incidence of, and dependency from, any recurrent stroke (using the modified Rankin Scale) or TIA within 90 days analysed using ordinal logistic regression with adjustment for prognostic factors. Baseline imaging features of brain frailty were adjudicated centrally by neuroimaging experts.

Results: 1080/3096 (34.9%) participants were on an antiplatelet agent prior to their stroke/TIA and were older, more likely to be male, had more co-morbidities and dependency, and more baseline imaging features of brain frailty than those not on prior antiplatelets. They had a higher incidence of, and dependency from, recurrent stroke or TIA at day 90: 86 (8%) vs. 112 (5.6%), adjusted common OR 1.40, 95%CI 1.02-1.92, p = 0.036; the result was neutralised when adjusted for brain frailty. Randomisation to triple vs. guideline therapy did not influence this effect.

Conclusions: Participants taking prior antiplatelets were frailer and had a higher incidence and severity of recurrent stroke or TIA at 90 days compared with those not on prior antiplatelets prior to adjustment for brain frailty.

Trial registration: ISRCTN47823388.

Background and purpose: In recent years, resting-state functional magnetic resonance imaging (rs-fMRI) has been widely used in the study of Parkinson's disease (PD), but the findings have not yet reached consensus. Besides, no studies have been conducted to standardize meta-analyses by combining the amplitude of low-frequency fluctuation (ALFF), fractional amplitude of low-frequency fluctuation (fALFF), and regional homogeneity (ReHo) functional indicators of PD.

Methods: A whole-brain voxel-wise meta-analysis was performed on resting-state functional imaging studies that explored differences in spontaneous functional brain activity between individuals with PD and healthy controls (HCs) using the Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) software.

Results: A total of 59 independent functional imaging studies (88 datasets) with 2591 individuals with PD and 1804 HCs were included. The results of the main meta-analysis revealed decreased resting-state regional functional activity in the left lenticular nucleus, the putamen, and the left supplementary motor area in PD patients compared to HCs, and no brain regions with significantly increased functional activity were identified. In the subsequent jackknife sensitivity analyses, these results showed high robustness and no significant heterogeneity or publication bias was observed.

Conclusion: This functional meta-analysis not only revealed robust and consistent brain regions with altered spontaneous functional activity in PD, but also helped to deepen our understanding of the complex neuropathological mechanisms of PD.

Introduction: The Romberg Test (RT) is a traditional bedside test of static balance. However, its nonspecific original description and focus on proprioceptive deficits have limited its diagnostic utility for vestibular dysfunction. We used gyroscopic measurements of trunk sway at the body's center of mass, time to fall, and a Subjective Instability score (SI) to gain more detailed insights than the binary outcomes typically used in clinical practice.

Objective: To evaluate whether specific patterns of sway and sway perception during the RT and its variants differentiate individuals with vestibular and proprioceptive deficits from healthy controls (HC).

Methods: We assessed 18 patients with chronic imbalance, divided into three groups: unilateral vestibular loss, bilateral vestibular loss, and isolated sensory predominant peripheral neuropathy (SPPN). Six healthy individuals served as HCs. All participants underwent clinical history, physical examination, and ancillary nerve conduction and vestibular tests when appropriate. Each performed eight stance tasks with simultaneous SI scoring and trunk sway recording.

Results: Trunk sway for eyes closed on foam was significantly greater in vestibulopathy than in neuropathy patients (p < 0.05). Conversely, SPPN patients showed greater imbalance on firm ground (eyes closed) than on foam. SPPN patients also had the greatest mismatch between objective and subjective instability on firm ground. Tandem tasks were less useful for group differentiation. No correlation was found between fall direction and the more hypofunctioning vestibulo-ocular reflex (VOR) side in vestibular patients.

Conclusion: The main distinguishing feature between vestibular and somatosensory ataxia across tasks are the differing sway patterns between firm and foam surfaces.

Background: Previous studies have found substantial heterogeneity in the effects of physical activity (PA) of different intensities on cognitive function. This study aimed to explore the association between PA levels and cognitive impairment and clarify the dose-response relationship among older adults in China.

Methods: This was a cross-sectional study, using data from the 2018 China Health and Retirement Longitudinal Study (CHARLS). We explored the association between PA levels and cognitive impairment using logistic regression, subgroup analysis, and restrictive cubic spline (RCS) analysis.

Results: Among the 3354 older participants, those who performed moderate intensity PA (MPA) showed a significant association with decreased odds ratio (OR) of cognitive impairment after adjusting for all confounding factors (OR = 0.58, 95% CI: 0.43 ~ 0.80). Subgroup analysis demonstrated consistent effects across all subgroups (P > 0.05). The results of the RCS analysis revealed a non-linear "J"-shaped dose-response relationship between PA levels and cognitive impairment (P _nonlinear < 0.05), with the lowest OR at around 1600 MET-min/wk.

Conclusion: MPA has greater benefits for cognitive function compared to light intensity PA, whereas vigorous intensity PA does not appear to offer additional protective benefits. PA is a dose-dependent factor associated with cognitive impairment in Chinese older adults, and approximately 1,600 MET-min/wk represents the optimal PA level for minimizing the risk of cognitive impairment. These findings can help offer more scientific PA recommendations to reduce or delay the development of cognitive impairment in older adults.

Background: Botulinum toxin (BoNT) is first-line therapy for cervical dystonia (CD), yet treatment response is heterogeneous. Patient-centered outcomes may be better captured by Goal Attainment Scaling (GAS) than by examiner-rated motor scales. We aimed to identify clinical factors influencing BoNT response in CD using GAS.

Methods: We conducted a retrospective two-center study including adults with CD treated with BoNT between January 2011 and August 2025. Treatment response was assessed using GAS T-scores. The primary outcome was achieving GAS ≥ 50 after the first session; the secondary outcome was achieving GAS > 50 in at least one session during follow-up.

Results: Eighty-seven patients were included (74.7% female; median age 68 years; median follow-up 4 years). Patients with focal cervical dystonia were significantly more likely to achieve a GAS score ≥ 50 after the first treatment session than those with non-focal forms (segmental, multifocal, or generalized dystonia; OR 5.667; 95% CI 1.853-17.326; p = 0.001). Failure to achieve a GAS score > 50 was significantly associated with the presence of other neurological disorders (OR 0.284; p = 0.020) or concomitant movement disorders (OR 0.211; p = 0.010). Ultrasound guidance was not associated with higher GAS scores.

Conclusion: Focal dystonia and absence of neurological comorbidities were associated with better BoNT response. Ultrasound guidance did not confer measurable benefit in this real-world cohort. GAS may support individualized treatment evaluation in CD.

Background: Parkinson's disease (PD) is one of the most common neurodegenerative disorders, characterized by motor symptoms in addition to non-motor symptoms that significantly impact the quality of life. While levodopa remains the gold standard for PD treatment, chronic use is associated with motor complications, including the "wearing-off" phenomenon and dyskinesia. IPX203, a novel extended-release carbidopa-levodopa (CD-LD) formulation, combines immediate-release granules with extended-release effects to maintain therapeutic plasma levels longer, potentially improving motor symptom management for PD patients.

Methods: A computer literature search of PubMed, Scopus, Web of Science, Google Scholar, and Cochrane Library was conducted using relevant keywords. Records were screened for eligible studies and data were extracted and synthesized using Review Manager version 4.5 for Windows. Sensitivity analysis was conducted to investigate the efficacy of IPX203 against IR CD-LD.

Results: Four RCTs with a total of 712 patients were eligible for the final analysis. The mean difference (MD) of change in the main outcomes from baseline to endpoint favored IPX203 over IR CD-LD (UPDRS) (MD = -6.80, 95% CI: [-9.38, -4.23]; p < 0.00001). change in the off time favored IPX203 over IR CD-LD after sensitivity analysis (MD = -2.42, 95% CI: [-3.12, -1.71]; P < 0.00001). The mean difference (MD) of change in the " good on" time favored IPX203 over IR CD-LD after sensitivity analysis (MD = 2.15, 95% CI: [1.45, 2.86]; P < 0.00001). None of the adverse events were significantly higher in the case of IPX203 compared to IR CD-LD.

Conclusion: IPX203 shows a significant potential in improving motor functions, reducing "off" time while increasing "good on" time. This makes IPX203 a valuable addition to current PD treatment strategies.

Objective: Epidemiological studies have suggested that single nucleotide polymorphisms (SNPs) in the interleukin-10 (IL-10) gene may contribute to the etiology of multiple sclerosis (MS). However, the results to date have been inconsistent, even contradictory.

Methods: A meta-analysis was conducted to investigate the potential association between IL-10 SNPs and MS susceptibility. Five English-language databases (PubMed, Embase, Web of Science, CNKI, and Wanfang) were searched for relevant studies. Crude odds ratios (OR) and 95% confidence intervals (CI) were calculated to assess the relationship between IL-10-1082 A > G (rs1800896), -819T > C (rs1800871), -592 A > C (rs1800872) polymorphisms, their haplotypes, and MS susceptibility. Publication bias, sensitivity analyses, and cumulative analyses were performed to evaluate the robustness and reliability of the findings.

Results: Fourteen articles (30 independent case-control studies) were included, revealing significant associations between the - 1082 A > G polymorphism and MS susceptibility in the general population (G vs. A: OR = 1.14, 95%CI = 1.05-1.24, P = 0.002, I² = 18.6%; AG vs. AA: OR = 1.32, 95%CI = 1.15-1.52, P < 0.001, I² = 36.1%; GG vs. AA: OR = 1.30, 95%CI = 1.10-1.55, P = 0.003, I² = 25.0%; AG + GG vs. AA: OR = 1.31, 95%CI = 1.15-1.49, P < 0.001, I² = 35.8%) and several subgroup models. Furthermore, the mutant GCC haplotype also exhibited a significant risk on MS susceptibility.

Conclusion: In summary, this current meta-analysis suggested that the IL-10 gene polymorphisms may be the substantial factors for the development of MS.

Introduction: Reperfusion Treatment(RT) options for Acute Ischemic Stroke(AIS) within 24 hours include: intravenous thrombolysis(IVT)(within 4.5 hours) and/or mechanical thrombectomy(MT). The utilization of benefits in 'real world' scenario, especially in Lower-Middle Income countries(LMICs) is not known. We aimed to determine the 'real-world' utilization and effectiveness of RT.

Patients and methods: In a single-center prospective cohort study, we collected data of all AIS patients coming within 24 hours. Patients receiving RT(IVT/MT/both) and those who were ineligible and received medical management (MM) were compared for the clinical, radiological characteristics and outcomes at 90-days assessed by modified Rankin Scale (mRS). The secondary outcomes were poor outcome at 90 days(mRS 3-6), Barthel Index(BI), Caregiver Strain Index(CSI), Stroke Specific Quality of Life(SSQoL) and mortality.

Results: In the study period (January 2022-September 2023), there were 302 patients. The mean age was 55.9(SD:15.7) years and majority were males (64.9%). Patients who underwent RT (42.7%(129/302)) had similar clinical characteristics, except for lesser time to presentation, better Glasgow Coma Scale(GCS), and better median ASPECTS. IVT was given to 33.4%(101/302) and MT in 14.6%(44/302). The mRS at 90-days was significantly better in the RT group (RT:1(0;3), MM:3(1;5);P <0.001). RT was an independent protective factor (OR: 0.3(0.2;0.4); p-value:<0.001) for worse outcome (mRS 3-6). Other factors associated with mRS 3-6 at 90-days in multivariate analysis were high NIHSS and low ASPECTS at presentation.

Conclusions: RT is feasible and effective in LMICs. Since the burden of stroke is increasing in LMICs and mean age of stroke is lower, post-stroke disability prevention by RT is an important intervention.