Journal of Central Nervous System Disease最新文献

Cognitive impairment encompasses a spectrum of disorders marked by acquired deficits in cognitive function, potentially leading to diminished daily functioning and work capacity, often accompanied by psychiatric and behavioral disturbances. Alzheimer's disease (AD) and Post-stroke cognitive impairment (PSCI) are significant causes of cognitive decline. With the global population getting older, AD and PSCI are becoming major health concerns, underscoring the critical necessity for successful treatment options. In recent years, various non-invasive biophysical stimulation techniques, including ultrasound, light, electric, and magnetic stimulation, have been developed for the treatment of central nervous system diseases. Preliminary clinical studies have demonstrated the feasibility and safety of these techniques. This review discuss the impact of 40 Hz multisensory stimulation on cerebral function, behavioral outcomes, and disease progression in both animal models and individuals exhibiting cognitive deficits, such as AD and PSCI. Furthermore, it summarizes the potential neural pathways involved in this therapeutic modality by synthesizing evidence from a variety of studies within the field. Subsequently, it evaluates the existing constraints of this technique and underscores the potential advantages of 40 Hz multisensory stimulation therapy for individuals with cognitive deficits, with the goal of enhancing the management and care of AD and PSCI.

Background: In conjunction with more sensitive culture and molecular diagnostic testing modalities, simultaneous or sequential infection with more than 1 vector borne zoonotic pathogen is being increasingly documented in human patients. On a frequent basis, many people are exposed to apparently healthy, but infected, domestic and wild animals, the arthropod vectors with which these animals have co-evolved, and the bacterial, protozoal and other pathogens for which various animals are reservoirs. Unsuspected zoonotic transmission by scratch, bite, or vector exposures can result in chronic, indolent, or potentially life-threatening infections.

Methods: In December 2016, at 2 years of age, a male child residing in Ontario, Canada received facial scratches from a feral cat. In August 2018, seizures began 8 days after the child developed a focal, suspected insect bite rash. In June 2019, potential mold toxicity in the child's bedroom was assessed by fungal culture and urinary mycotoxin assays. Beginning in January 2022, Bartonella spp. serology (indirect fluorescent antibody assays), polymerase chain reaction (PCR) amplification, DNA sequencing, and enrichment blood and brain cultures were used on a research basis to assess Bartonella spp. bloodstream and central nervous system (brain biopsy) infection. In 2024, using recently developed PCR and DNA sequencing targets, Babesia species infection was retrospectively assessed due to the rash observed in 2018.

Results: Although there was historical cat and suspected tick exposures, serological testing for Bartonella henselae and Borrelia burgdorferi were repeatedly negative. Sequential neurodiagnostic testing partially supported a diagnosis of Rasmussen's encephalitis. Astrogliosis was the only brain biopsy histopathological abnormality. Bartonella henselae DNA was amplified and sequenced from enrichment cultures of brain tissue. Retrospectively, Babesia odocoilei and Babesia divergens-like MO-1 infections were confirmed by amplification and sequencing of DNA extracted from enrichment blood cultures processed in January 2022, from blood and brain tissue cultures in June 2022, and blood in January and June 2023.

Conclusions: Infection with B. henselae, B. odocoilei, and B. divergens-like MO-1, complicated by mycotoxin exposure, created a complex clinical scenario for this child, his parents, and his doctors.

Under normal physiological conditions, gut microbiota and host mutually coexist. They play key roles in maintaining intestinal barrier integrity, absorption, and metabolism, as well as promoting the development of the central nervous system (CNS) and emotional regulation. The dysregulation of gut microbiota homeostasis has attracted significant research interest, specifically in its impact on neurological and psychiatric disorders. Recent studies have highlighted the important role of the gut- brain axis in conditions including Alzheimer's Disease (AD), Parkinson's Disease (PD), and depression. This review aims to elucidate the regulatory mechanisms by which gut microbiota affect the progression of CNS disorders via the gut-brain axis. Additionally, we discuss the current research landscape, identify gaps, and propose future directions for microbial interventions against these diseases. Finally, we provide a theoretical reference for clinical treatment strategies and drug development for AD, PD, and depression.

Background: Mild acute ischemic stroke (AIS), characterized by a National Institutes of Health Stroke Scale (NIHSS) score of 5 or less, can lead to significant long-term disabilities. Reperfusion therapies like intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT) are commonly used in AIS, but their efficacy and safety in mild stroke cases remain unclear.

Objectives: This meta-analysis aims to clarify the prevalence of mild AIS and evaluate the outcomes of reperfusion therapy, specifically IVT and EVT, in terms of functional recovery, mortality, stroke recurrence, and adverse events such as symptomatic intracerebral hemorrhage (sICH), intracerebral hemorrhage (ICH), and early neurological deterioration (END).

Design: A meta-analysis was conducted following PRISMA guidelines to combine and assess the results of independent studies examining the use of reperfusion therapies in patients with mild AIS.

Data sources and methods: A systematic search of PubMed, Embase, and Cochrane databases was performed. Studies assessing mild AIS prevalence and the outcomes of reperfusion therapy were included. Random effects modelling was applied to evaluate associations between reperfusion therapy and clinical outcomes at 90 days.

Results: Fifty-six studies, including 474 778 patients, were analyzed. The pooled prevalence of mild stroke was 54% among all AIS cases, 29% in IVT-treated patients, and 9% in EVT-treated patients. Reperfusion therapy was associated with significantly increased odds of sICH (OR 2.92), ICH (OR 2.20), and END (OR 2.37). However, no significant association was found with excellent functional outcomes (OR 0.93), good functional outcomes (OR 0.91), mortality (OR 1.14), or stroke recurrence (OR 0.93) at 90 days. Variations were observed between different reperfusion subgroups.

Conclusion: Mild AIS is prevalent, and reperfusion therapy in these cases is linked to higher rates of adverse events without a clear benefit in functional outcomes or mortality. These findings support the need for selective reperfusion therapy in mild stroke patients. The proposed SAFE framework-Selective use of IVT, Assessment of individual factors, Focus on EVT for large vessel occlusion (LVO), and Establishment of region-specific guidelines-may help guide clinical decisions. Further research should refine patient selection criteria and explore adjunctive therapies.

Background: Parkinson's Disease (PD) varies widely among individuals, and Artificial Intelligence (AI) has recently helped to identify three disease progression subtypes. While their clinical features are already known, their gene expression profiles remain unexplored.

Objectives: The objectives of this study were (1) to describe the transcriptomics characteristics of three PD progression subtypes identified by AI, and (2) to evaluate if gene expression data can be used to predict disease subtype at baseline.

Design: This is a retrospective longitudinal cohort study utilizing the Parkinson's Progression Markers Initiative (PPMI) database.

Methods: Whole blood RNA-Sequencing data underwent differential gene expression analysis, followed by multiple pathway analyses. A Machine Learning (ML) classifier, namely XGBoost, was trained using data from multiple modalities, including gene expression values.

Results: Our study identified differentially expressed genes (DEGs) that were uniquely associated with Parkinson's disease (PD) progression subtypes. Importantly, these DEGs had not been previously linked to PD. Gene-pathway analysis revealed both distinct and shared characteristics between the subtypes. Notably, two subtypes displayed opposite expression patterns for pathways involved in immune response alterations. In contrast, the third subtype exhibited a more unique profile characterized by increased expression of genes related to detoxification processes. All three subtypes showed a significant modulation of pathways related to the regulation of gene expression, metabolism, and cell signaling. ML revealed that the progression subtype with the worst prognosis can be predicted at baseline with 0.877 AUROC, yet the contribution of gene expression was marginal for the prediction of the subtypes.

Conclusion: This study provides novel information regarding the transcriptomics profiles of PD progression subtypes, which may foster precision medicine with relevant indications for a finer-grained diagnosis and prognosis.

Background: Parkinson's disease (PD) is one of the most common neurodegenerative disorders. Previous research has confirmed that isofraxidin can reduce macrophage expression and inhibit peripheral inflammation. However, its effects on the central nervous system remain underexplored.

Objective: This study aims to determine whether isofraxidin offers protective effects against PD.

Methods: To assess the effects of isofraxidin, motor performance changes in LPS-induced PD mice were evaluated using rotarod, pole-climbing, and beam-walking tests. Striatal damage was examined through [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) positron emission tomography (PET) imaging, and dopaminergic neurotoxicity was assessed using tyrosine hydroxylase (TH) staining. Microglial accumulation and activation were monitored with Iba-1 staining, while LPS-induced inflammation was examined via TNF-α and IL-1β staining.

Results: Isofraxidin pre-treatment significantly improved LPS-induced motor dysfunction, as evidenced by better performance in the rotarod, pole-climbing, and beam-walking tests. [¹⁸F]FDG PET imaging showed that isofraxidin restored glucose uptake in the striatum, countering LPS-induced damage. Furthermore, Iba-1 staining revealed that isofraxidin markedly inhibited LPS-induced microglial activation and accumulation. TNF-α and IL-1β staining indicated a reduction in inflammation with isofraxidin treatment. Additionally, TH staining supported the neuroprotective role of isofraxidin on dopaminergic neurons.

Conclusions: Isofraxidin exhibits notable neuroprotective properties by mitigating LPS-induced parkinsonian behaviors, microglial activation, inflammation, and dopaminergic neuron damage. These results highlight isofraxidin's potential as a therapeutic intervention for PD.

Background: Sneddon's syndrome is a rare thrombotic vasculopathy characterized by the coexistence of both cerebrovascular events and livedo reticularis.

Objective: This review aims to raise awareness among physicians by discussing the whole clinical spectrum of the disease. Typically, Sneddon syndrome presents in middle-aged women with a cerebrovascular accident and a preexisting skin rash, which is livedo reticularis. Diagnosis is primarily clinical, relying on a high index of suspicion. Management focuses mainly on reducing the risk of cerebral infarctions and alleviating symptoms.

Conclusion: Further research is necessary to better understand the disease's nature, which will contribute to improving early diagnosis and optimal management.

Stroke is a significant health concern impacting society and the health care system. Reperfusion therapy for acute ischemic stroke and standard rehabilitative therapies may not always be effective at improving post-stroke neurological function, and developing alternative strategies is particularly important. Vagus nerve stimulation (VNS) is a treatment option currently approved by the Food and Drug Administration (FDA) for intractable epilepsy, refractory depression, primary headache disorders, obesity, and moderate to severe upper-limb motor dysfunction in chronic ischemic stroke patients. Moreover, VNS has demonstrated potential efficacy in various conditions, including autoimmune diseases, disorders of consciousness, Alzheimer's disease, Parkinson's disease, traumatic brain injury, stroke, and other diseases. Although the popularity and application of VNS continue to increase rapidly, the field generally lacks a consensus on the optimal stimulation parameters. The stimulation parameters for VNS are directly related to the clinical outcome, and determining the optimal stimulation conditions for VNS has become an essential concern in its clinical application. This review summarizes the current evidence on VNS for stroke in preclinical models and clinical trials in humans, paying attention to the current types and stimulation parameters of VNS, highlighting the mechanistic pathways involved in the beneficial effects of VNS, critically evaluating clinical implementation challenges and proposing some suggestions for its future research directions. Achieving safe and effective clinical transformation of VNS requires further animal and clinical studies to determine the optimal stimulation parameters and therapeutic mechanisms.

Background: The paddle lead (PL) and cylindrical lead (CL) remain the main implant categories in spinal cord stimulation (SCS) for treating neuropathic pain. Surgeons often complain about the greater trauma associated with PL implantation, while percutaneous endoscopic technique offers a promising approach for minimizing the trauma associated to PL implantation. However, there remains a dearth of real-world case study on endoscopy-assisted CL implantation.

Purpose: This study aimed to demonstrate the endoscopic-assisted approach and outcomes of CL implantation in SCS for managing neuropathic pain.

Research design: A retrospective case series.

Study sample: Patients aged 18 years and above with chronic neuropathic pain persisting for at least three months, refractory to standardized conservative treatment, were enrolled between January 2021 and March 2023.

Data collection and analysis: The surgical key steps including puncture, working cannula placement, endoscopic laminotomy and endoscopic CL introduction were demonstrated. Characteristics as demographics, follow-up time, visual analog scale (VAS) score, pain disability index (PDI) score and patient-reported outcomes measurement information system (PROMIS) scale were assessed.

Results: Successful CL implantation under endoscopy was achieved in all patients, including 3 with failed back surgery syndrome, 2 with complex regional pain syndrome and 2 with chronic pelvic pain. No spinal cord injuries, dural tears, lead migration, lead fractures, or postoperative infections were observed. VAS score of regional pain, PDI score as well as PROMIS of patient's quality of life were all significantly improved after surgery.

Conclusion: Percutaneous endoscope-assisted CL implantation offered a new alternative technique for SCS in managing neuropathic pain.