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RATIONALE AND KEY POINTS: Hospital admissions can be challenging for people with Parkinson's disease, in part because of the lack of understanding, among some healthcare professionals, of the importance of administering antiparkinsonian medicines on time. This article outlines the steps that nurses can take to optimise medicines management for people with Parkinson's disease who are admitted to hospital. • Pharmacotherapy is the primary treatment for Parkinson's disease and aims to increase dopamine levels in the brain to relieve symptoms. • People with Parkinson's disease require careful administration, titration, adjustment and monitoring of their antiparkinsonian medicines regimen, which is highly individualised. • It is crucial that people with Parkinson's disease take their antiparkinsonian medicines at exactly the right time, since the inaccurate timing of these medicines can have significant adverse health implications. REFLECTIVE ACTIVITY: 'How to' articles can help to update your practice and ensure it remains evidence-based. Apply this article to your practice. Reflect on and write a short account of: • How this article might improve your practice when undertaking medicines management for people with Parkinson's disease in hospital. • How you could use this information to educate nursing students or your colleagues on optimising medicines management for people with Parkinson's disease in hospital.

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OBJECTIVE: To systematically review the literature of existing evidence on the measurement properties of the Quality of Life in Neurological Disorders (Neuro-QoL) measurement system among neurorehabilitation populations. DATA SOURCES: The Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) guided this systematic review in which we searched nine electronic databases and registries, and hand-searched reference lists of included articles. STUDY SELECTION: Two independent reviewers screened selected articles and extracted data from 28 included studies. DATA EXTRACTION: COSMIN's approach guided extraction and synthesizing measurement properties evidence (insufficient, sufficient), and the modified GRADE approach guided synthesizing evidence quality (very-low, low, moderate, high) by diagnosis. DATA SYNTHESIS: Neuro-QoL has sufficient measurement properties when used by individuals with Huntington's disease, Multiple Sclerosis, Parkinson's disease, stroke, lupus, cognitive decline, and amyotrophic lateral sclerosis. The strongest evidence is for the first four conditions, where test-retest reliability, construct validity, and responsiveness are nearly always sufficient (GRADE: moderate-high). Structural validity is assessed only in multiple sclerosis and stroke but is often insufficient (GRADE: moderate-high). Criterion validity is sufficient in some stroke and Huntington's disease domains (GRADE: high). Item response theory analyses were reported for some stroke domains only. There is limited, mixed evidence for responsiveness and measurement error (GRADE: moderate-high), and no cross-cultural validity evidence CONCLUSIONS: Neuro-QoL domains can describe and evaluate patients with Huntington's disease, multiple sclerosis, Parkinson's disease, and stroke, but predictive validity evidence would be beneficial. In the other conditions captured in this review, a limited number of Neuro-QoL domains have evidence for descriptive use only. For these conditions, further evidence of structural validity, measurement error, cross-cultural validity and predictive validity would enhance the use and interpretation of Neuro-QoL.

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BACKGROUND: A field of study that uses telerehabilitation (TR) is neurorehabilitation; however, standards for medical and technological applications, medicolegal and ethical regulations, and other aspects of neuro-TR are still being developed. OBJECTIVE: To address the prerequisites and barriers for implementing TR in neurorehabilitation in the light of present findings. METHODS: A narrative review was conducted based on specific questions about the prerequisites for neuro-TR and barriers to its implication. According to a foreground search strategy in the context of neurorehabilitation using TR in neurological patient population, PubMed, EMBASE and Cochrane databases were searched and reviewed. RESULTS: Barriers and prerequisites for neuro-TR were mostly grouped under the categories of administrative/organizational, human (beneficiaries/providers), technical, and ethical. Apart from the technical framework, knowledge and the presence of an administrative leader responsible for overseeing TR are crucial prerequisites. The internet and technological constraints rank highest among the barriers. CONCLUSION: Since neuro-TR is relatively new with minimal guidelines and regulations, highly technologic, and lack of established practices, it is imperative to determine and fully comprehend the criteria for its uses. After the prerequisites are established, it is imperative to recognize and address implementation constraints, which may differ depending on the community's infrastructure and neurologic condition.

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Pre-hospital end-tidal carbon dioxide (EtCO2) monitoring and arterial to end-tidal carbon dioxide gradient (Pa-EtCO2) have been associated with mortality in patients with traumatic brain injury. Our study aimed to analyze the association between alveolar EtCO2 or Pa-EtCO2 and mortality in patients admitted in intensive care unit (ICU) with neurological injuries. In our retrospective analysis from using large de-identified ICU databases (MIMIC-III and -IV and eICU databases), we included 2872 ICU patients with neurological injuries, identified according to the International Classification of Diseases (ICD-9 and -10), who underwent EtCO2 monitoring. We performed logistic regression and extended Cox regression to assess the association between mortality and candidate covariates, including EtCO2 and Pa-EtCO2. In-hospital mortality was 26% (n = 747). In univariate analysis, both the Pa-EtCO2 gradient and EtCO2 levels during the first 24 h were significantly associated with mortality (for a 1 mmHg increase: OR = 1.03 [CI95 1.016-1.035] and OR = 0.94 [CI95 0.923-0.953]; p < 0.001). The association remained significant in multivariate analysis. The time-varying evolution of EtCO2 was independently associated with mortality (for a 1 mmHg increase: HR = 0.976 [CI95 0.966-0.985]; p < 0.001). The time-varying Pa-EtCO2 gradient was associated with mortality only in univariate analysis. In neurocritical patients, lower EtCO2 levels at admission and throughout the ICU stay were independently associated with mortality and should be avoided.

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BACKGROUND: Cardiovascular, respiratory, and nervous system diseases have high morbidity and mortality rates, but the causal relationship between air pollution and these diseases remains controversial. METHODS: We conducted a large-scale genome-wide association (GWAS) study using Mendelian randomization (MR) to investigate the association between air pollution like Nitrogen dioxide (NO2), Nitrogen oxides (NOX), Particulate matter with diameter<2.5µm (PM2.5), Particulate matter with diameter<10µm (PM10) and cardiovascular, respiratory, and nervous system diseases, including acute myocardial infarction, heart failure, asthma, chronic obstructive pulmonary disease (COPD), pneumonia, stroke and Parkinson's disease. This study included 337,199 patients with acute myocardial infarction, 178,726 patients with heart failure, 463,010 patients with asthma, 462,933 patients with COPD, 486,484 patients with pneumonia, 484,598 patients with stroke, and 482,730 patients with Parkinson's disease. All genetic tools were identified from GWAS. The association effects of environmental pollution and these diseases were investigated using MR analysis, sensitivity analysis with heterogeneity, pleiotropy test, and leave-one-out test. RESULTS: Our MR analysis showed the association between NOX and the development of COPD and stroke (Odds ratio (OR)=1.010, 95 % Confidence interval (CI): 1.000～1.020, P=0.046; OR=1.017, 95 %CI:1.003-1.031, P=0.019), the association between PM2.5 and the development of asthma, COPD and stroke (OR=1.013, 95 %CI:1.003-1.024, P=0.011; OR=1.010, 95 %CI:1.000-1.019, P=0.035; OR=1.019, 95 %CI:1.004-1.033, P=0.012). No significant associations were found between the rest of the air pollution exposures and diseases. Leave-one-out sensitivity analysis showed stable results. CONCLUSIONS: The study clarifies the relationship between air pollution and cardiovascular, respiratory, and nervous system diseases, providing valuable evidence for environmental pollution prevention and population health monitoring, and provides a clear direction and evidence for the subsequent investigation of the association between air pollution and diseases.

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BACKGROUND: Adults with physical or intellectual disability are less active than those without disability. OBJECTIVE: To review literature regarding sport participation in adults with physical or intellectual disability. Specifically, to examine characteristics of available studies including participants, interventions, outcomes, and impact. METHODS: A scoping review was completed. Searches of 6 databases and a trial registry plus citation tracking were undertaken. Two independent reviewers screened items for eligibility and extracted data about the studies, participants, interventions, and outcomes. A single reviewer extracted data to quantify impacts of sport participation, classified as favorable, insignificant, or unfavorable. RESULTS: 164 studies involving 11,642 participants were included. Most studies (128/164) used a cross-sectional design. Most participants were men (81%) with physical disability (135/164), and spinal cord injury was the most prevalent underlying health condition (54%). Most studies evaluated a mix of sports (83/164) in a disability-specific context (159/164), with basketball or wheelchair basketball being the most common individual sport (28/164). Physical impairment was the most frequently reported outcome domain (85/334 results). Sports participation impact was classified as 55% favorable, 42% insignificant, and 3% unfavorable. CONCLUSIONS: There were many favorable and few unfavorable outcomes for participation in sport for adults with physical or intellectual disability. More research is needed to address the evidence gaps of gender, health condition, and type of sport, and to use more rigorous research designs to evaluate the effects of sport participation. While new evidence is generated, we suggest adults with physical or intellectual disability be encouraged to engage in sport. REGISTRATION: PROSPERO registration number CRD42018104379.

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BACKGROUND: Multiple sclerosis is a common inflammatory neurological disease among young adults and is the tenth leading cause of the global burden of disease. Existing common treatments such as pharmacological and palliative therapies do not control the neurodegenerative process or cure multiple sclerosis. Numerous epidemiological surveys, randomised controlled trials, and systematic reviews with meta-analyses support the effects of physical activity on health-related outcomes among patients with multiple sclerosis. Moreover, bibliometric analysis can provide a broad evidence synthesis beyond systematic reviews and meta-analyses, allowing researchers and other stakeholders to obtain a one-stop overview of this research field. Therefore, this bibliometric analysis aims to provide insight into the knowledge structure of the field of physical activity for multiple sclerosis over the past three decades, and to predict emerging research trends. METHODS: This study strictly complied with step-by-step guidelines of bibliometric analysis, combining performance analysis and science mapping. Four indexes from the Web of Science Core Collection were selected as data sources, and articles and review articles in the field of physical activity for multiple sclerosis from 1994 to 2023 were included in this analysis. Mircrosoft Excel, RStudio, VOSviewer 1.6.20, and CiteSpace 6.3.R1 (64-bit) Advanced were used to perform performance analysis and science mapping. RESULTS: Over the past three decades, this field published a total of 1,271 documents, with the scientific output showing a rapid upward trend over the past two decades. Robbert W Motl was the most prolific author in this field, with a total of 300 publications. The USA contributed nearly half of the publications in this field (549 documents), and the University of Illinois System was the institution with the highest number of publications (222 documents). Multiple Sclerosis and Related Disorders was the journal that published the highest number of documents in this field (117 documents), while more than a third of this field's publications were included in the category: Clinical Neurology (438 documents). The Reference co-citation analysis identified three main research trends, including shifts in research methodology, changes in health outcomes in randomised controlled trials, and shifts in different types of physical activity interventions. Combining the results from reference co-citation analysis and citation burst analysis, the combination of behaviour change technique and telerehabilitation may be the emerging research trend. CONCLUSION: This bibliometric analysis identifies rapid growth in the field of physical activity for multiple sclerosis over the past two decades. Moreover, the combination of performance analysis and science mapping provides insight into knowledge structure in this field and informed future research trends for researchers and the relevant stakeholders.

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BACKGROUND: Patients with genetic deficiency of the adaptor protein complex 4 (AP-4) exhibit earlyonset developmental delay, spastic diplegia, intellectual disability, speech impairment. The phenotype overlaps with other hereditary spastic paraplegias and cerebral palsies. Febrile seizures are common at onset. Epilepsy has been described in more than half of cases, arising in early infancy often with status epilepticus, but no typical seizure semiology or electroencephalographic features have been identified thus far. PURPOSE: We aimed to specifically investigate the epileptological characteristics of the syndrome to unveil possible biomarkers of seizure development and prognosis in AP-4 deficiency. METHODS: Observational cohort study on patients with bi-allelic pathogenic variants in AP-4 subunits and epilepsy. We focused on the seizure semiology, electroencephalographic characteristics and response to antiseizure medications. RESULTS: Patients harboured pathogenic variants in AP4S1 (n = 5) or AP4M1 (n = 1). The phenotype included spastic paraparesis, intellectual disability, speech/language impairment, microcephaly, and MRI evidence of hypoplasia of the corpus callosum. In 66 % of the patients, febrile seizures preceded the onset of epilepsy, which spanned from infancy to adolescence (range=14 months-13 years). Absences (66 %) and focal motor seizures (50 %) were common. No patient met the criteria for drug-resistance. Peculiar electroencephalographic features arose after the epilepsy onset and persisted at long-term follow-up: bilateral and asynchronous focal discharges combined with independent diffuse spike-wave-discharges (100 %) and reflex abnormalities (66 %). CONCLUSION: In AP-4 complex disease, epilepsy could arise beyond early infancy, until adolescence, with variable combination of generalized and focal seizures. The prognosis was favourable. We observed a common electroencephalographic signature - combined focal/generalized and reflex abnormalities - which may constitute a biomarker of AP-4 deficiency with epilepsy, applicable to inform genetic testing and disentangle the differential diagnosis.

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The underlying mechanisms of diseases affecting the central nervous system (CNS) remain unclear, limiting the development of effective therapeutic strategies. Remarkably, cellular senescence, a biological phenomenon observed in cultured fibroblasts in vitro, is a crucial intrinsic mechanism that influences homeostasis of the brain microenvironment and contributes to the onset and progression of CNS diseases. Cellular senescence has been observed in disease models established in vitro and in vivo and in bodily fluids or tissue components from patients with CNS diseases. These findings highlight cellular senescence as a promising target for preventing and treating CNS diseases. Consequently, emerging novel therapies targeting senescent cells have exhibited promising therapeutic effects in preclinical and clinical studies on aging-related diseases. These innovative therapies can potentially delay brain cell loss and functional changes, improve the prognosis of CNS diseases, and provide alternative treatments for patients. In this study, we examined the relevant advancements in this field, particularly focusing on the targeting of senescent cells in the brain for the treatment of chronic neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, and multiple sclerosis) and acute neurotraumatic insults (e.g., ischemic stroke, spinal cord injury, and traumatic brain injury).

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Objectives. This study aimed to evaluate the influence of individual characteristics (sex, age, body mass index [BMI] and smoking habits) on the tolerance time, pain ratings and rewarming time of hand cold stress testing (CST). Methods. We included 153 subjects (63% men) working in a Swedish open-pit mine (participation rate 41%). The right hand was immersed in 3 °C circulating water for up to 45 s. Pain ratings were registered every fifth second using a visual analog scale. Results. The tolerance time (mean ± standard deviation) was 35 ± 12 s for men and 29 ± 14 s for women (p = 0.007). The youngest age group (18-29 years) had the longest tolerance time, while the oldest group (54-65 years) had the shortest (p = 0.005). Women had significantly higher pain ratings than men after 5, 10 and 25 s. The group with the highest BMI had the shortest rewarming time (p < 0.001). Conclusions. Age and sex influenced the tolerance time of hand CST, while only sex affected the pain ratings and BMI the rewarming time. When performing CST in future studies, these parameters should be considered.

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In the last ten years, stem cell (SC) therapy has been extensively used to treat a range of conditions such as degenerative illnesses, ischemia-related organ dysfunction, diabetes, and neurological disorders. However, the clinical application of these therapies is limited due to the poor survival and differentiation potential of stem cells (SCs). Extracorporeal shock wave therapy (ESWT), as a non-invasive therapy, has shown great application potential in enhancing the proliferation, differentiation, migration, and recruitment of stem cells, offering new possibilities for utilizing ESWT in conjunction with stem cells for the treatment of different systemic conditions. The review provides a detailed overview of the advances in using ESWT with SCs to treat musculoskeletal, cardiovascular, genitourinary, and nervous system conditions, suggesting that ESWT is a promising strategy for enhancing the efficacy of SC therapy for various diseases.

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This study aimed to investigate the therapeutic potential of human adipose-derived mesenchymal stem cells (hADSCs) modified with recombinant adeno-associated virus (rAAV) carrying the vascular endothelial growth factor 165 (VEGF165) gene in peripheral nerve injury (PNI). The hADSCs were categorized into blank, control (transduced with rAAV control vector), and VEGF165 (transduced with rAAV VEGF165 vector) groups. Subsequently, Schwann cell differentiation was induced, and Schwann cell markers were assessed. The sciatic nerve injury mouse model received injections of phosphate-buffered saline (PBS group), PBS containing hADSCs (hADSCs group), rAAV control vector (control-hADSCs group), or rAAV VEGF165 vector (VEGF165-hADSCs group) into the nerve defect site. Motor function recovery, evaluated through the sciatic function index (SFI), and nerve regeneration, assessed via toluidine blue staining along with scrutiny of Schwann cell markers and neurotrophic factors, were conducted. Modified hADSCs exhibited enhanced Schwann cell differentiation and elevated expression of Schwann cell markers [S100 calcium-binding protein B (S100B), NGF receptor (NGFR), and glial fibrillary acidic protein (GFAP)]. Mice in the VEGF165-hADSCs group demonstrated improved motor function recovery compared to those in the other three groups, accompanied by increased fiber diameter, axon diameter, and myelin thickness, as well as elevated expression of Schwann cell markers (S100B, NGFR, and GFAP) and neurotrophic factors [mature brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF)] in the distal nerve segment. rAAV-VEGF165 modification enhances hADSC potential in PNI, promoting motor recovery and nerve regeneration. Elevated Schwann cell markers and neurotrophic factors underscore therapy benefits, providing insights for nerve injury strategies.

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Hematopoietic stem cell transplantation (HSCT) is a medical procedure used mainly for the treatment of onco-hematologic disorders. Over the last two decades, autologous HSCT has been explored for the treatment of neurologic autoimmune diseases (ADs), being multiple sclerosis (MS) the most frequent indication in this setting. HSCT is characterized by the sequential administration of a conditioning regimen (CR) and the infusion of hematopoietic stem cells (HSCs), previously collected either by the individual himself in the autologous transplant (AHSCT), or by a healthy donor in allogeneic HSCT. CR consists of the administration of high-dose chemotherapy and/or total body irradiation (TBI), that in ADs is usually associated with an immunodepleting serotherapy, either by an animal-derived polyclonal serum or a monoclonal antibody (MoAb), to induce intense immunosuppression. CRs are classified according to the European Society for Blood and Marrow Transplantation (EBMT) guidelines for HSCT in ADs in three grades of intensity according to the degrees of depletion of the hemato-lymphopoietic system induced. In the present chapter, after a brief overview of mobilization and CR adopted in the neurologic autoimmune setting, the role of chemotherapy in HSCT will be discussed, providing a historical perspective on the use of different regimens and summarizing the available evidence on potential associations between CR and outcomes.

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BACKGROUND: Primary central nervous system lymphoma is rare, and primary central nervous system T cell lymphoma is relatively uncommon, contributing to < 5% of all cases. Lymphomatosis cerebri, a rare subtype of primary central nervous system lymphoma, is characterized by extensive white-matter lesions on magnetic resonance imaging and nonspecific symptoms, such as cognitive decline and depression. Reports of lymphomatosis cerebri in adult T cell leukemia/lymphoma are limited. CASE PRESENTATION: A 49-year-old Japanese man gradually developed insomnia, anorexia, and weight loss over a 2-month period following work-related promotion. Initially diagnosed with depression, his condition rapidly deteriorated with cognitive decline and motor dysfunction. Despite various treatments, his symptoms persisted within a month. Upon admission, the presence of neurological abnormalities suggestive of a central nervous system disorder raised suspicion of a cerebral lesion. Diagnostic tests revealed extensive brain lesions on imaging and the presence of atypical lymphocytes (flower cells) in the cerebrospinal fluid. The patient was diagnosed with lymphomatosis cerebri due to adult T cell leukemia/lymphoma, a rare presentation in the literature. Due to irreversible brainstem damage and poor neurological prognosis, aggressive treatment was not initiated, and the patient died, with an autopsy confirming the diagnosis. CONCLUSION: Lymphomatosis cerebri with adult T cell leukemia/lymphoma is very rare. It is crucial to promptly consider lymphomatosis cerebri as a differential diagnosis, particularly in cases of rapid cognitive decline and poor treatment response. Recognition of lymphomatosis cerebri as an important differential diagnosis for cognitive decline, and depression is necessary for timely intervention and management. Further research is required to better understand this unique and rare presentation in adult T cell leukemia/lymphoma.

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INTRODUCTION: Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by lymphocytic infiltrates in the exocrine glands. Carpal tunnel syndrome (CTS) is suggested to be more frequent among SS patients than in the general population. The aim of this study was to seek associations between the CTS and the laboratory and clinical findings of SS patients. METHODS: Fifty patients diagnosed with primary SS (pSS) were examined. Clinical evaluation by a rheumatologist and electrophysiological studies were conducted. Data on laboratory tests results was collected. Control group consisted of 50 sex and age-matched individuals with osteoarthritis (OA). RESULTS: Out of 50 patients in the study group 27 (54%) were diagnosed with CTS. The prevalence of CTS among 50 individuals in the control group was 8%. Among pSS patients with CTS the joint involvement was not more common than in those from the non-CTS group [15 vs. 13 (p = 0.945)]. There was an expected difference in sleep disorders [18 vs. 9 (p = 0.012)] and paresthesia [23 vs. 13 (p = 0.024)]. The major finding was a significant difference in elevated beta2-microglobulin (B2MG) [23 vs. 13 (p = 0.024)]. Other studied factors, suggested in the literature as significant in the pSS-related neuropathy, were not statistically different between the groups. CONCLUSION: Our study confirms that CTS is more prevalent among pSS patients than in the general population and suggests that a new approach is required towards the pathogenesis of this phenomenon. We hypothesize that CTS is more associated with an overall disease activity than joint involvement as such.

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CONTEXT: Diabetic peripheral neuropathy (DPN) results in an enormous burden and reduces the quality of life for patients. Considering there is no specific drug for the management of DPN, traditional Chinese medicine (TCM) has increasingly drawn attention of clinicians and researchers around the world due to its characteristics of multiple targets, active components, and exemplary safety. OBJECTIVE: To summarize the current status of TCM in the treatment of DPN and provide directions for novel drug development, the clinical effects and potential mechanisms of TCM used in treating DPN were comprehensively reviewed. METHODS: Existing evidence on TCM interventions for DPN was screened from databases such as PubMed, the Cochrane Neuromuscular Disease Group Specialized Register (CENTRAL), and the Chinese National Knowledge Infrastructure Database (CNKI). The focus was on summarizing and analyzing representative preclinical and clinical TCM studies published before 2023. RESULTS: This review identified the ameliorative effects of about 22 single herbal extracts, more than 30 herbal compound prescriptions, and four Chinese patent medicines on DPN in preclinical and clinical research. The latest advances in the mechanism highlight that TCM exerts its beneficial effects on DPN by inhibiting inflammation, oxidative stress and apoptosis, endoplasmic reticulum stress and improving mitochondrial function. CONCLUSIONS: TCM has shown the power latent capacity in treating DPN. It is proposed that more large-scale and multi-center randomized controlled clinical trials and fundamental experiments should be conducted to further verify these findings.

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INTRODUCTION: Psychiatric comorbidities have a significant impact on patients' quality of life and often go undetected in neurologic practice. The aim of this study was to describe and characterize psychiatric comorbidities among patients hospitalized due to a neurologic disorder in mainland Portugal. METHODS: A retrospective observational study was performed by analyzing hospitalization with a primary diagnosis of neurologic disorder defined as categories 76, 77, 79 - 85, 95, 109 of the Clinical Classification Software for International Classification of Diseases, Ninth Revision, Clinical Modification, occurring between 2008 and 2015 in adult patients (≥ 18 years of age). Psychiatric comorbidities were determined as the presence of a secondary diagnosis belonging to the Clinical Classification Software categories 650 to 670. RESULTS: A total of 294 806 hospitalization episodes with a primary diagnosis of a neurologic disorder were recorded in adult patients between 2008 - 2015 in Portuguese public hospitals. Approximately 26.9% (n = 79 442) of the episodes had a recorded psychiatric comorbidity (22.1%; 32.2%, female versus male hospitalizations). Patients with registered psychiatric comorbidities were younger (66.2 ± 16.2 vs 68.6 ± 17.2 with no psychiatric comorbidities, p < 0.001), presented lower all-cause in-hospital mortality rates, and significantly longer mean hospital stays. 'Delirium, dementia, amnestic and other cognitive disorders' were recorded in 7.4% (n = 21 965) of the hospitalizations, followed by alcohol-related disorders in 6.5% (n = 19 302) and mood disorders in 6.1% (n = 18 079). Epilepsy/seizures were the neurologic disorders with the highest proportion of recorded psychiatric comorbidities (39.9%). CONCLUSION: Psychiatric comorbidities were recorded in more than a quarter of the hospitalizations with a primary diagnosis of a Neurologic disorder. Psychiatric comorbidities varied among neurological disorders and were associated with different demographic and clinical features.

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Ginsenosides are the primary component discernible from ginseng, including Rb1, Rb2, Rd, Rg1, Rg2, and compound K, and so forth. They have been shown to have multiple pharmacological activities. In recent years, more and more studies have been devoted to the neuroprotection of various ginsenosides against neurological diseases and their potential mechanisms. This paper comprehensively summarizes and reviews the neuroprotective effects of various ginsenosides on neurological diseases, especially acute and chronic neurodegenerative diseases, and their mechanisms, as well as their potential therapeutic applications to promote neuroprotection in disease prevention, treatment, and prognosis. Briefly, ginsenosides exert effective neuroprotective effects on neurological conditions, including stroke, Alzheimer's disease, Parkinson's disease, and brain/spinal cord injuries through a variety of molecular mechanisms, including anti-inflammatory, antioxidant, and anti-apoptotic. Among them, some signaling pathways play important roles in related processes, such as PI3K/Akt, TLR4/NF-κB, ROS/TXNIP/NLRP3, HO-1/Nrf2, Wnt/ß-catenin, and Ca2+ pathway. In conclusion, the present study reviews the research progress on the neuroprotective effects of ginsenosides in the last decade, with the aim of furnishing essential theoretical underpinning and effective references for further research and exploration of the multiple medicinal values of Chinese herbal medicines and their small molecule compounds, including ginseng and panax ginseng. Because there is less evidence in the existing clinical studies, future research should be focused on clinical trials in order to truly reflect the clinical value of various ginsenosides for the benefit of patients.

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Central nervous system (CNS) disorders are one of the leading health problems today, accounting for a large proportion of global morbidity and mortality. Most these disorders are characterized by high levels of oxidative stress and intense inflammatory responses in degenerated neuronal tissues. While extensive research has been conducted on CNS diseases, but few breakthroughs have been made in treatment methods. To date, there are no disease-modifying drugs available for CNS treatment, underscoring the urgent need for finding effective medications. Bee venom (BV), which is produced by honeybee workers' stingers, has been a subject of interest and study across various cultures. Over the past few decades, extensive research has focused on BV and its therapeutic potentials. BV consists a variety of substances, mainly proteins and peptides like melittin and phospholipase A2 (PLA2). Research has proven that BV is effective in various medical conditions, including pain, arthritis and inflammation and CNS disorders such as Multiple sclerosis, Alzheimer's disease and Parkinson's disease. This review provides a comprehensive overview of the existing knowledge concerning the therapeutic effects of BV and its primary compounds on various CNS diseases. Additionally, we aim to shed light on the potential cellular and molecular mechanisms underlying these effects.

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