Neurological Sciences最新文献

The CNS presents a unique challenge to therapeutic intervention due to its sophisticated organization, the protective blood-brain barrier (BBB), and the low regenerative potential of neural tissue. Over the last few decades, nanotechnology has emerged as a revolutionary technology capable of transforming the diagnosis and treatment of CNS diseases, thereby offering new hope to patients with previously incurable neurodegenerative diseases. This review highlights the therapeutic and diagnostic potential of newer types of nanomaterials-i.e., nanoliposomes (NLs), metallic nanoparticles (MNPs), and carbon nanotubes (CNTs)-which have been found to cross the blood-brain barrier (BBB) and deliver drugs with enhanced specificity and efficacy. Nanoparticle-based therapies have revolutionized drug delivery, gene therapy, in vivo imaging, and molecular profiling for CNS diseases. However, despite such advancements, hurdles remain, particularly in terms of biocompatibility, long-term safety, and site-specific activity within complex biological systems. Herein, we summarize recent advances in the construction of smart nanocarriers and multi-functional platforms for overcoming physiological and pharmacological challenges in CNS therapy. Finally, we emphasize the urgent need for interdisciplinary studies to unlock the full clinical potential of nanotechnology in neurology and answer outstanding questions regarding toxicity, immune responses, and scalability for human application.

Background: Agitation is one of the most distressing neuropsychiatric symptoms in patients with dementia due to Alzheimer's disease (AD), significantly impacting patients' quality of life and increasing caregiver burden. Brexpiprazole, a serotonin-dopamine modulator, shows promise for managing agitation. This meta-analysis evaluates the efficacy and safety in managing agitation associated AD.

Method: A comprehensive literature search was conducted across PubMed, Cochrane, Scopus, Embase and ClinicalTrials.gov from inception until January 2025. We pooled dichotomous outcomes as risk ratios (RR) and continuous outcomes as mean differences (MD) with 95% confidence intervals (CI), using random-effects models. Heterogeneity was assessed using I² and X² statistics. A p-value of < 0.05 was considered statistically significant. All the calculations were performed using RevMan 5.4.

Result: This meta-analysis included 4 studies involving 1440 patients (944 vs. 496) suffering from agitation associated with dementia in AD. Brexpiprazole significantly reduced agitation on CMAI (MD: -3.94 [-6.21 to -1.67], p < 0.001) and NPI-NH (MD: -0.67 [-1.08 to -0.26], p = 0.002) with optimal efficacy at 2-3 mg/day. SAS scores worsened slightly (MD: 0.38 [0.18-0.58], p = 0.0002) while MMSE (p = 0.06) and CGI-S (p = 0.06) remained stable. No significant differences emerged in serious adverse events, mortality, dizziness, or extrapyramidal effects (all p > 0.05).

Conclusion: Brexpiprazole effectively reduces agitation in AD without major safety concerns, though mild motor effects were noted. Study limitations include moderate heterogeneity and short trial durations. Future research should explore long-term outcomes and patient stratification.

Background: The Benefit Finding Scale (BFS) is a 17-item measure assessing the perception of positive contributions to one's life deriving from stressful and life-threatening conditions such as illnesses. We aimed to investigate construct validity (structural validity, measurement invariance between sub-samples, and convergent/divergent validity) and reliability (internal consistency) of the Italian version of the BFS in persons with multiple sclerosis (PwMS) and their caregivers.

Methods: We used confirmatory factor analysis (CFA) to assess structural validity in terms of the proposed three-factor structure of the BFS. We performed multi-group CFA to assess measurement invariance between PwMS and their caregivers. To assess convergent/divergent validity, we calculated correlations of the BFS subscales with instruments measuring affect (PANAS), life satisfaction (SWLS), social support (MSPSS), depression (BDI-II), and quality of life (SF-36 and MSQoL-54). To appraise internal consistency, we calculated Cronbach's alpha.

Results: A total of 1359 PwMS and their caregivers completed the study. The three-factor structure of the BFS showed good fit (RMSEA 0.06; CFI 0.92; SRMR 0.05). Configural, metric and scalar invariance were confirmed. Convergent/divergent validity was supported. The BFS showed good internal consistency for 'Acceptance and adjustment' (alpha 0.82), 'Family relations and sense of connectedness' (alpha 0.84) and 'Personal growth and authenticity' (alpha 0.85).

Conclusions: Results support the BFS as a valid and invariant three-factor measure of benefit finding among Italian PwMS and their caregivers. This scale use in clinical practice could help health professionals track participants' experience of positive changes under adverse circumstances, as assets in managing stress and promoting illness adjustment.

Background: The optimal timing for initiating direct oral anticoagulants (DOACs) after acute ischemic stroke or transient ischemic attack (TIA) in patients with nonvalvular atrial fibrillation (NVAF) remains uncertain.

Objective: To determine whether early initiation of DOACs is superior to delayed initiation in preventing new vascular events.

Methods: This guideline was developed using the GRADE approach and includes a systematic review and meta-analysis of four randomized controlled trials (TIMING, ELAN, OPTIMAS, START) enrolling 6,664 patients. Outcomes were selected via Delphi consensus. Meta-analyses used random-effects models, with certainty of evidence rated per GRADE methodology.

Results: Early DOAC initiation was associated with a trend toward fewer recurrent ischemic events (RR 0.77, 95% CI 0.52-1.14) and thromboembolic events (RR 0.73, 95% CI 0.50-1.06), with no increase in symptomatic intracranial hemorrhage (RR 0.93, 95% CI 0.44-1.97) or major extracranial bleeding (RR 0.84, 95% CI 0.42-1.69). Certainty of evidence was low due to imprecision. An individual patient data meta-analysis from CATALYST collaboration further supported early treatment in patients with minor to moderate stroke.

Recommendations: We recommend early DOAC initiation within 4 days in patients with minor to moderate stroke to prevent new vascular events. Early DOAC initiation over delayed treatment is indicated in patients with severe acute ischemic stroke to prevent new vascular events.

Conclusion: Early DOAC initiation appears safe and potentially more effective than delayed treatment, supporting a shift toward earlier anticoagulation in selected patients with NVAF and recent ischemic stroke.