To explore the correlation between blood urea nitrogen/albumin (B/A) ratio, central nervous system specific protein S100 (S100β), cardiac troponin I (cTnI) and the severity assessment and prognosis in patients with moderate-to-severe acute carbon monoxide poisoning (ACMP). A retrospective cohort study was performed, enrolling patients with moderate-to-severe ACMP admitted to the Harrison International Peace Hospital from March 1, 2023 to December 31, 2025 as the study subjects. Baseline clinical data at admission were recorded, including coma duration, time from poisoning to presentation, etc. Blood routine examination, electrolyte levels, liver function, blood glucose, C-reactive protein (CRP), blood lactic acid (Lac), blood urea nitrogen (BUN), albumin (Alb), cTnI, S100β, as well as BUN, Alb, cTnI, S100β at admission and 3 days after admission were collected, and the B/A ratio was calculated. Patients were followed up for 60 days to assess clinical prognosis. According to the severity of the patients' condition, they were stratified into the moderate poisoning group and the severe poisoning group; further, based on the occurrence of delayed carbon monoxide encephalopathy (DEACMP) during the 60-day follow-up, they were divided into the good prognosis group and the poor prognosis group. Pearson correlation analysis was used to explore the associations of B/A ratio, S100β, and cTnI with the severity of ACMP patients and the occurrence of DEACMP; stepwise logistic regression analysis was used to analyze the influencing factors of DEACMP occurrence in ACMP patients; receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of B/A ratio, S100β, cTnI, and their combined detection for DEACMP occurrence in ACMP patients. A total of 178 patients with moderate-to-severe ACMP were enrolled, including 91 in the moderate poisoning group and 87 in the severe poisoning group; 157 in the good prognosis group and 21 in the poor prognosis group. In terms of disease severity, compared with the moderate poisoning group, the severe poisoning group had faster pulse and respiratory rates upon admission, longer coma duration and time from poisoning to treatment, higher levels of blood glucose, CRP, Lac, and BUN, and lower Alb levels (all P<0.05). In addition, the B/A ratio, S100β, and cTnI levels in the severe poisoning group were all higher than those in the moderate poisoning group at admission and 3 days after admission (all P<0.05). Compared with admission, the B/A ratio increased and the cTnI level decreased in the moderate poisoning group at 3 days after admission (both P<0.05), while S100β showed no significant change. In the severe poisoning group, there was no statistically significant difference in the B/A ratio, S100β, and cTnI levels at 3 days after admission compared to those at admission. In terms of prognosis, compared with the good prognosis group, the poor prognosis group had longer coma duration and time from poisoning to treatment at admission, a higher proportion of severe poisoning patients, higher levels of blood glucose, CRP, Lac, and BUN, and lower Alb levels (all P<0.05). In addition, the B/A ratio, S100β, and cTnI levels at admission and 3 days after admission were higher in the poor prognosis group than in the good prognosis group (all P<0.05). Correlation analysis showed that the B/A ratio, S100β, and cTnI levels at admission and 3 days after admission were correlated with the severity of ACMP and the occurrence of DEACMP (both P<0.05). Stepwise logistic regression analysis showed that the elevated B/A ratio [at admission: odds ratio (OR)=1.272, 95% confidence interval (95%CI)=1.028-1.573; on admission day 3: OR=1.170, 95%CI was 0.947-1.463], S100β (on admission: OR=1.065, 95%CI was 1.007-1.127; on admission day 3: OR=1.112, 95%CI was 1.060-1.165), and cTnI (on admission: OR=1.358, 95%CI was 1.055-1.748; on admission day 3: OR=1.201, 95%CI was 1.008-1.432) at admission and 3 days after admission were all risk factors for DEACMP in patients with ACMP (all P<0.05). ROC curve analysis showed that the area under the curve (AUC) for the combined prediction of DEACMP occurrence using B/A ratio, S100β, and cTnI on admission and on admission day 3 were 0.872 and 0.904, respectively. The sensitivities were 95.2% and 85.7%, respectively, and the specificities were 68.8% and 80.3%, respectively. The combined prediction efficacy of the three markers on admission was superior to that of the degree of intoxication and individual detection of the three markers, and the combined prediction efficacy of the three markers on admission day 3 was superior to that of the degree of intoxication, coma duration, and individual prediction of the three markers. Furthermore, the combined detection of the three markers on admission day 3 had a superior predictive efficacy compared to that on admission (all P<0.05). Patients with moderate to severe ACMP are at higher risk of developing DEACMP when their early circulating levels of the B/A ratio, S100β, and cTnI are elevated. Combined detection of these three biomarkers facilitates early screening for DEACMP, with the highest predictive value observed at 3 days after admission.
The epidemiology of primary autoimmune diseases of the central nervous system is poorly described in Caribbean and Afro-descendant children. We studied the incidence, clinical and biological characteristics, immunological profiles, and prognosis of these diseases in Martinique. We conducted a descriptive, retrospective, monocentric, population-based study from January 2010 to July 2024 including all children aged 0-17 years hospitalized for autoimmune encephalitis, multiple sclerosis, neuromyelitis optica spectrum disorder (NMOSD), or myelin oligodendrocyte glycoprotein-associated disease (MOGAD) in the pediatric units of the Martinique University Hospital. The sequelae were assessed using an Expanded Disability Status Scale score. Twenty-five children were hospitalized for primary autoimmune disease of the CNS in Martinique and 16% were admitted to intensive care. The median age at onset was 14 years (2-17 years). The incidence rates found were 0.34 per 100,000 person-years (95% confidence interval 0.09-0.88) for NMOSD and 0.52 per 100,000 person-years (0.19-1.13) for MOGAD, and 0.60 per 100,000 person-years (0.24-1.24) for multiple sclerosis. The immunological profile of NMOSD/MOGAD was 70% seropositive (4 aquaporin-4 and 3 myelin oligodendrocyte glycoprotein). First-line treatment was high-dose corticosteroid therapy in most cases (88%). Long-term sequelae were rare in our population and mortality was null. Our study showed an increase in the incidence of NMOSD diseases compared to international studies and no significant difference in the incidence rates of the other autoimmune disorders of the CNS in children. Outcomes were comparable to European and North American countries in our population. The immunological profile showed a high proportion of anti-aquaporin-4 antibodies compared to the literature.
Myelin enables rapid action potential conduction and axonal support, and its disruption underlies diverse neurological disorders. Its assessment is essential for studying development, plasticity, and repair of the nervous system (NS), and for diagnosing demyelinating diseases and evaluating remyelination therapies. Multiple histological methods detect myelin, each with trade-offs in sensitivity, cost, and reproducibility. Among them, Eriochrome Cyanine R (EC-R) is a simple, affordable myelin stain widely used in thin sections, but remains poorly standardized, and underexplored in thick vibratome sections. Here we describe and validate a simple, inexpensive, solvent-free EC-R protocol for central and peripheral nervous system tissue across seven vertebrate species and multiple demyelinating conditions. The method replaces subjective microscopic differentiation with fixed, time-controlled incubations scaled to section thickness, improving reproducibility. Using perfusion and immersion-fixed samples, we show that the protocol yields homogeneous myelin labeling with sharp white/gray matter contrast in whole brains, cortical slabs, spinal cord, and peripheral nerves. Thick sections stained with EC-R preserve 3-dimensional tissue architecture, resolve single myelinated axons and intracortical bands, and can be combined with Nissl-like counterstains and immunohistochemistry. Developmental series in neonatal rats reveal expected PNS-CNS myelination gradients, while experimental demyelination models and naturally occurring diseases (canine distemper and human multiple sclerosis) illustrate the method's ability to delineate lesion cores, perilesional gradients, and associated glial and immune activation. This standardized EC-R approach provides a robust and versatile tool for comparative neuroanatomy, experimental neuropathology, and translational studies of myelination, demyelination, and remyelination, as well as for the clinical diagnosis of myelin-related disorders.
We sought to improve test utilization for 8 autoimmune antibody panels. Three interventions (test ordering guidance, clinical pathway guidance, and duplicate test blocking) were implemented at 6-month intervals. Over 3 years, we recorded trends in test volumes, duplicate tests, and positive results. We conducted chart reviews for two 3-month periods 1 year apart to assess the impact on patient Antibody Prevalence in Epilepsy and Encephalopathy (APE2) scores. Comparing the first 6 months with the last 6 months of the 3-year study, we observed a 36.5% decrease in overall test volume and a 95.5% reduction in duplicate tests. The final true-positive rate based on clinical diagnosis was low, however, at only 1.6% (40/2550) of tests performed and 1.3% (24/1883) of patients tested. Performance did not improve over the study period. Chart reviews (n = 194) showed only 8 of 106 (7.5%) patients had an APE2 score of at least 4 in January through March 2023, and 12 of 88 (13.6%) met this threshold in January through March 2024. Two of 20 total patients with an APE2 score of at least 4 had a new diagnosis of autoimmune central nervous system disease compared with 0 of 174 patients with a score below 4 (P < .001), affirming the predictive value of the scorecard. Although reductions in test volume and duplicate testing were observed, clinicians continued to order a substantial number of tests for patients whose clinical picture was not suggestive of autoimmune epilepsy or encephalopathy. Although there was some improvement in appropriate ordering when assessed by retrospective APE2 scores, this value did not reach statistical significance.
BACKGROUND: Limited data are available regarding clinical and social determinants influencing treatment outcomes among patients with central nervous system (CNS) tuberculosis (TB) in high-resource settings. METHODS: We performed a retrospective cohort study of patients with CNS TB from January 2011 to June 2022 at the San Francisco Department of Public Health TB Clinic and the University of California, San Francisco Medical Center. Data were abstracted from cases of confirmed or suspected CNS TB treated with anti-TB therapy. Logistic regression models were used to identify sociodemographic and clinical factors associated with mortality and functional and cognitive impairment among survivors. RESULTS: Of 54 cases of CNS TB, 26% were microbiologically-confirmed. 31% resided in the top 3 deciles of social disadvantage. Over a mean follow-up of 10.2 months, cumulative mortality was 22%. Among survivors, 40% exhibited functional impairment and 38% demonstrated moderate to severe cognitive dysfunction. In adjusted models, having public insurance (aOR 14.94, 95% CI 1.58-141.29, p = 0.018) or residing in a highly deprived neighborhood (aOR 7.66, 95% CI 1.46–40.22, p = 0.016) was associated with functional and cognitive impairment, respectively. Additional risk factors for adverse clinical outcomes included older age, diabetes mellitus, severe disease at presentation (e.g., altered mentation, requiring intubation) and hydrocephalus. CONCLUSIONS: In this high-resource setting, cumulative mortality and disability rates among patients treated for CNS TB were comparable to outcomes reported in studies from low and middle-income countries where TB is endemic. Although limited by the modest sample size, this study demonstrates a potential link between social disadvantage and poor CNS TB outcomes, highlighting persistent inequities in TB care even within a well-resourced health system. If these findings are confirmed in a larger study, implementing a comprehensive approach that addresses the social determinants of health affecting individuals at risk for TB will be essential to improving outcomes in this devastating infection.
To analyze the treatment response in patients with primary angiitis of the central nervous system (PACNS) in a large vasculitis cohort. In this single-center retrospective observational study, we assessed treatment, relapses, remission, and outcome of patients with PACNS. We pooled the patients' relapses under different treatments as well as various immunotherapies. Multivariate logistic regression analysis was performed to determine factors independently associated with relapse and those associated with good functional status. The time of observation was 96 months. The cohort comprised 80 patients, with 38 diagnosed with pathologically confirmed PACNS and 42 with clinically diagnosed PACNS, with a median follow-up duration of 18 months (range 3-96). Treatment comprised acute-phase induction therapy with high-dose corticosteroids, alone or combined with immunosuppressive agents, followed by remission-phase maintenance immunosuppressive therapy, primarily with cyclophosphamide, rituximab, or mycophenolate mofetil. Following treatment, 49 patients (61.3%) achieved remission and 70 (87.5%) attained favorable functional outcomes. The overall relapse rate was 35%. Group 3 demonstrated significantly higher baseline disease severity (p < 0.05). Multivariate analysis identified seizures and cognitive impairment as predictors of relapse. This study demonstrates that a majority of PACNS patients exhibit a favorable response to therapy. For patients presenting with more severe disease at diagnosis, long-term maintenance therapy following remission induction with glucocorticoids or immunosuppressive agents is required.
Multiple sclerosis is a chronic demyelinating disease of the central nervous system caused by an immune-mediated inflammatory process. Its aetiology remains unclear, and numerous pathogenetic theories have been proposed. The diversity of clinical manifestations and the lack of reliable biomarkers make diagnosis challenging. Serum neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) have been investigated as potential biomarkers for disease progression and response to disease-modifying therapies; however, their specificity and sensitivity remain variable, particularly in the presence of other conditions associated with neuronal damage and neurodegeneration. This retrospective study analysed serum NfL and GFAP levels in 149 patients with multiple sclerosis and 40 healthy controls. Additionally, the association between the two biomarkers was evaluated in patients with and without polyneuropathy to assess their reliability and prognostic value for disease severity and progression. Serum NfL was found to be a reliable marker of disease activity and progression. In contrast, GFAP demonstrated limited specificity and was not suitable as a single, independent biomarker. The presence of co-existing polyneuropathy influenced biomarker levels and complicated their interpretation. Serum NfL shows promise as a reliable biomarker for monitoring disease activity and progression in multiple sclerosis. However, GFAP should not be used independently due to its limited specificity. Co-existing polyneuropathy may further reduce the reliability of these biomarkers, highlighting potential diagnostic challenges in clinical practice.
To our knowledge, a systematic comparison of nutrients contribution to mortality in large scale cohort of middle-aged to elderly individuals has not yet been done. We aim to investigate the associations between most of the available nutrients and all-cause and disease-specific mortality, and explored their joint effect on mortality risk. A total of 208,312 participants from the UK Biobank (UKB) with baseline 24-hour dietary recall data were enrolled. Cox proportional hazards models were used for a nutrients-wide association analysis of all-cause mortality and disease-specific mortality. Mixed-effects analyses were further conducted to evaluate the combined effects of nutrients significantly associated with mortality risk by Bayesian kernel machine regression (BKMR) and Quantile G-Computation (Qgcomp) regression models. No significant associations were found between total energy, total protein, total lipid, or total carbohydrate intake and all-cause mortality risk. However, energy density was moderately and positively associated with all-cause mortality (HR=1.017, 95%CI: 1.004-1.030). Nutrient type and quality exhibited significant impacts: plant-derived protein (HR=0.995, 95%CI: 0.992-0.998), plant-derived lipids (HR=0.997, 95%CI: 0.995-0.999), were negatively associated with all-cause mortality. Among carbohydrates, starch, lactose, and intrinsic/milk sugars showed protective effects, while free sugars, non-milk extrinsic sugars, sucrose, and maltose were positively associated with increased mortality risk. For minerals and vitamins, copper, manganese, total iron, non-haem iron, vitamin E, riboflavin, biotin, and pantothenic acid exhibited inverse associations with all-cause mortality. Mixed-effects analyses revealed cumulative inverse trends of beneficial nutrients and positive trends of harmful nutrients on mortality risk, with manganese, maltose, biotin, and niacin being key contributors. Disease-specific analysis showed that energy density and certain sugars were positively associated with neoplasms mortality; multiple sugars were linked to nervous system disease mortality; and alcohol, maltose were positively associated with digestive system disease mortality, while most macronutrients, minerals, vitamins, and fibre had protective effects. Sodium and chloride were positively associated with circulatory system disease mortality. Total intake of major macronutrients was not significantly associated with mortality risk, but nutrient type and quality played critical roles. Plant-derived nutrients, specific minerals, vitamins, dietary fibre, and natural carbohydrates were protective against mortality, whereas refined sugars and high energy density were detrimental. These findings highlight the importance of dietary quality in reducing mortality risk and provide evidence for developing targeted dietary recommendations.
Fibromyalgia syndrome (FMS) is a chronic condition characterised by the presence of complex multiple symptoms, often accompanied by psychiatric comorbidities and sleep problems. The wide spectrum of symptoms and comorbid problems complicates treatment and management of the ensuing disability and symptoms. Physiotherapy approaches and mind-body practices including yoga and mindfulness are among the non-pharmacological treatment methods commonly used in FMS treatment. While there is initial evidence for these interventions, definitive conclusions about their effectiveness are still lacking and research on their combined effectiveness is limited. Therefore, this study aims to evaluate the effectiveness of a multimodal integrative protocol, the PhYoMind (PYM) intervention, which combines specific physical therapy modalities with yoga and mindfulness practices on the overall impact of fibromyalgia and functional impairment. This monocentric study uses a parallel-group (1:1) randomised controlled design, in which the outcome assessor and statistician are blinded to group allocation. Individuals with a clinical diagnosis of FMS (n=40) will be included in the study (Cohen's f=0.675; α=0.05; power=0.80). Participants will be randomised to receive either PYM intervention in addition to Home Exercise (HE) programme or HE programme alone. The intervention period for both groups will last 8 weeks; PYM sessions will be held twice a week for 75 min each. The primary outcome is the broad disease impact and functional impairments measured by the total score of the Fibromyalgia Impact Questionnaire. Secondary outcomes include central sensitivity, as assessed by the Central Sensitisation Index; autonomic nervous system function, as measured objectively by heart rate variability; pain perception (current, average, worst), as assessed by the Visual Analogue Scale; fatigue, as assessed by the Multidimensional Fatigue Inventory; stress, as assessed by the Perceived Stress Scale; and sleep quality as assessed by the Pittsburgh Sleep Quality Index. Adherence and adverse events will be assessed for both interventions. Repeated measures ANOVA will be used to analyse the effect of time, intervention group and their interaction on primary and secondary outcomes under an intention-to-treat principle. Ethics approval was granted from the Ethics Committee at the Medical Faculty of Eberhard Karls Tuebingen University and at the University Hospital of Tuebingen (260/2025BO2) on 30 April 2025. The trial will be conducted in accordance with the updated principles of the Declaration of Helsinki. The study's findings will be disseminated and documented in a peer-reviewed publication, adhering to the Consolidated Standards of Reporting Trials guidelines. After completion of the study and publication of the results, participants who are interested will be offered a brief summary of the aggregated study findings. NCT07145788.
Glioblastoma (GBM) is the most aggressive and biologically heterogeneous tumor of the central nervous system, associated with dismal prognosis and frequent recurrence. Amplification of the epidermal growth factor receptor (EGFR) and EGFRvIII mutation are common alterations, yet their prognostic significance remains unclear. This systematic review evaluated whether clinical evidence supports a predictive association between EGFR amplification or EGFRvIII mutation and response to EGFR-targeted therapy in adults with recurrent GBM. PubMed, Embase and the Cochrane Library were searched (2010-2025) for studies of adults with recurrent GBM treated with EGFR-targeted therapies, with outcomes stratified by EGFR amplification and/or EGFRvIII. Screening, data extraction and risk-of-bias assessment were performed independently. Twelve studies (565 patients) met inclusion criteria. EGFR amplification was assessed in 11 studies and EGFRvIII in six using FISH, qPCR, RT-PCR, or NGS. Median overall survival ranged from 5.7 to 10.3 months and progression-free survival from 1.7 to 6.0 months, with no consistent survival benefit observed. EGFR amplification and EGFRvIII mutation have not demonstrated reliable predictive value for EGFR-targeted therapy in recurrent GBM. The available evidence is largely derived from heterogeneous, single-arm studies, limiting robust assessment of biomarker specific treatment response and therefore these alterations are not recommended to be used to guide off-trial treatment decisions in recurrent GBM.Protocol Registration: www.crd.york.ac.uk/prospero identifier is CRD420251071466. Recurrent glioblastoma is when a brain tumor called glioblastoma comes back after treatment or starts growing again after a period of improvement. Many of these tumors have changes in a gene called epidermal growth factor receptor (EGFR), including EGFR amplification and EGFRvIII mutations, but it is still unclear whether these changes help identify patients who might benefit from EGFR-targeted treatments.This review brought together the available clinical studies that looked specifically at adults with recurrent glioblastoma and EGFR-related gene changes. It focused only on studies that reported results for patients with these EGFR gene changes and the outcome of a number of different EGFR-targeted treatment protocols. Overall, the review found no clear or lasting benefit from EGFR-targeted therapies in patients with these tumor changes.The findings show that despite strong biological reasons to target EGFR, the current evidence does not support EGFR alterations as reliable markers of treatment response in recurrent glioblastoma. The review also highlights major differences in how these gene changes are tested and how trials are designed, making results hard to compare. Better standardized testing and more carefully designed clinical trials are needed to determine whether EGFR-targeted treatment has a true role in precision treatment for this disease.ARTICLE HIGHLIGHTSEGFR amplification and EGFRvIII mutation should not guide off-trial treatment in rGBM.Biomarker testing and outcome reporting remain highly heterogeneous across trials.Future trials require appropriate control arms and standardized prospective biomarker testing.
The glymphatic system plays a critical role in brain waste clearance and has been implicated in neurodegenerative diseases. Primary angle-closure glaucoma (PACG) is increasingly recognized as a neurodegenerative disorder extending beyond the eye. This study aimed to investigate glymphatic system function in patients with PACG using diffusion tensor imaging analysis along the perivascular space (DTI-ALPS). This cross-sectional study included patients with PACG and age- and sex-matched healthy controls. All participants underwent magnetic resonance imaging, including diffusion tensor imaging. The DTI-ALPS index was calculated to assess glymphatic function. Group differences and correlations with disease severity were analyzed. Patients with PACG showed a significantly lower whole-brain DTI-ALPS index compared with healthy controls (1.50 ± 0.14 vs 1.60 ± 0.15, P = .030; Cohen d = 0.63). Lower DTI-ALPS values were significantly correlated with worse visual field mean deviation and thinner retinal nerve fiber layer thickness (P < .05). Glymphatic system function appears to be impaired in PACG and is associated with disease severity. These findings provide further evidence supporting the concept of glaucoma as a neurodegenerative disease involving the central nervous system.
Invasive fungal infection (IFI) represents a significant global health challenge, particularly in paediatric populations, due to high mortality and severe long-term sequelae. This study aimed to characterize the epidemiological patterns and quantify the disease burden of IFI among hospitalised children in China. Data were obtained from the face sheets of discharge medical records collected between 2016 and 2022 from 30 tertiary children's hospitals, aggregated into the FUTang Updating medical REcords (FUTURE) database. Sociodemographic variables, disease spectrum, pathogen distribution, potential risk factors, length of stay (LOS), and overall disease burden among children with IFI were systematically analysed. A total of 1250 IFI cases were identified, revealing an upward trend in incidence since 2019. The pathogen distribution among the 485 episodes with available microbiological data included Candida (25.36%; 123/485), Aspergillus (23.71%; 115/485), Cryptococcus (22.06%; 107/485), Pneumocystis (21.44%; 104/485), Mucor (4.12%; 20/485), Talaromyces (1.24%; 6/485), Histoplasma (0.82%; 4/485), Blastomyces (0.62%; 3/485), and Sporotrichum (0.62%; 3/485). Disseminated infections accounted for 5.76% (72/1250) of all IFI. Among the 1178 non-disseminated IFI cases, pneumonia (73.34%, 864/1178), central nervous system (CNS) infections (15.53%, 183/1178), and bloodstream infections (8.66%, 102/1178) were the predominant disease types. The most prevalent risk factors were haematological malignancies and myelosuppression. Overall, 181 patients died during their hospitalisation, representing a mortality rate of 14.48%. The incidence of IFI among hospitalised children in tertiary centres in China has risen since 2019, with Candida, Aspergillus, and Cryptococcus identified as the predominant pathogens. These infections are associated with considerable mortality (14.48%). The findings highlight the urgent need for enhanced surveillance, earlier diagnosis, and targeted therapeutic strategies to reduce morbidity and mortality in this high-risk population.
During the first months following diagnosis and treatment of childhood-onset craniopharyngioma, a substantial proportion of patients experience rapid and marked weight gain. This frequently progresses to severe hypothalamic obesity, which results from hypothalamic injury caused either by the tumor itself or by therapeutic interventions. Hypothalamic obesity should be regarded as one manifestation within the broader clinical spectrum of hypothalamic syndrome. Given the pivotal role of hypothalamic nuclei in maintaining physiological homeostasis, hypothalamic syndrome encompasses a wide range of disturbances, including hypothalamic-pituitary hormone deficiencies, disruption of circadian rhythms, impaired regulation of hunger, satiety, and thirst, as well as thermoregulatory dysfunction and cognitive, sleep-related, and psychosocial impairments. Consequently, affected individuals often develop persistent obesity, chronic fatigue, excessive daytime sleepiness, and mood disturbances, which may contribute to social withdrawal, academic challenges, reduced participation in daily activities, and impaired quality of life. Over time, these patients are at increased risk for metabolic syndrome, cardiovascular disease, sustained reductions in quality of life, and premature mortality. Historically, the management of hypothalamic syndrome has been challenging for both patients and clinicians, as conventional obesity treatments, including lifestyle modification, dietary interventions, and physical activity, have shown limited long-term efficacy. Pharmacological approaches have likewise been unsatisfactory, either due to insufficient effectiveness or unacceptable adverse effects leading to their withdrawal from clinical use. The therapeutic impact of central nervous system stimulants and glucagon-like peptide-1 receptor agonists in acquired hypothalamic obesity remains inconsistent and subject to ongoing debate. Recent findings from a randomized controlled trial provide, for the first time, encouraging evidence that setmelanotide, a melanocortin-4 receptor agonist, may substantially improve outcomes in patients with hypothalamic dysfunction associated with hypothalamic obesity. The emergence of a safe and effective pharmacological therapy that addresses not only metabolic abnormalities but also key psychosocial features, such as hyperphagia and overall quality of life, may represent a significant advancement in the management of this complex condition and offers the potential to meaningfully improve outcomes in this highly burdened and underserved patient population.
population working or living in agriculture settings may experience important exposure to pesticides and other agents. Although some health effects associated with them are well known, for others (e.g., neurological diseases and lymphoid, hematopoietic and related tissue cancers) additional epidemiological evidence is needed. to investigate mortality for neurological diseases and cancer in workers employed in agriculture in Italy. case-control study using mortality data linked with working histories retrieved from the Italian National Social Insurance archive. countrywide mortality data from 2005 to 2018 were used. Cases were blue-collar workers with primary/middle school education who died from selected causes; controls were individuals with the same characteristics, but died from all other causes. Each participant was assigned to the economic sector in which he/she worked for the longest period. Cause-specific mortality odds ratios (MORs) adjusted for age class, educational level, year of death, and region of residence were estimated using logistic regression models in which exposure of interest was "ever/never" (or length of employment) in agriculture using the service sectors as (unexposed) reference category. Analyses were adjusted for or stratified by gender. MORs for causes of death within the groups of mental, behavioural and neurodevelopmental disorders (F01-F99), diseases of the nervous system (G00-G99), and malignant neoplasms (C00-C96)Results: about 64,000 workers employed in agriculture were included and compared with a control group of 107,000 workers in the service sector. Elevated mortality risk in agriculture workers was found for spinal muscular atrophy (MOR 1.26; 95%CI 1.03-1.56; 261 deaths) and Parkinson's disease (PD) (MOR 1.16; 95%CI 1.00-1.34; 742 deaths). As for cancer mortality, positive associations were found for non-follicular lymphoma (NFL) (MOR 1.59; 95%CI 1.03-2.46; 82 deaths), multiple myeloma (MM) (MOR 1.42; 95%CI 1.22-1.65; 546 deaths), and myeloid leukaemia (ML) (MOR 1.36; 95%CI 1.16-1.60; 474 deaths), as well as for stomach (MOR 1.30; 95%CI 1.20-1.41; 1,732 deaths), prostate (MOR 2.03; 95%CI 1.85-2.24, 1,582 deaths), and brain and central nervous system cancer (MOR 1.30; 95%CI 1.13-1.50; 601 deaths). PD, NFL, ML, cancers of skin, of connective and soft tissue, of prostate and of brain were found to involve mainly men. employment in agriculture has been associated with various health risks, some of which may be attributed to pesticides exposure. Although the use of the different agronomic categories of pesticides changed over time and some active ingredients were prohibited or limited, their health effects remain of concern for their large use, demanding further focused investigations and preventive measures.
Parkinson's disease (PD) is a rapidly growing global health challenge, with prevalence projected to reach 13-14 million cases by 2040. While aging and improved diagnostic awareness partly explain this trend, mounting evidence implicates environmental factors as critical contributors. This review synthesizes current literature on exposures such as pesticides, solvents, heavy metals, air pollutants, and infectious agents, emphasizing their mechanistic links to neurodegeneration. These factors interact with genetic susceptibility and aging, supporting the "multiple-hit" hypothesis, which posits that PD arises from cumulative insults rather than a single cause. Mitochondrial dysfunction, oxidative stress, neuroinflammation, and impaired protein clearance emerge as convergent pathways underlying dopaminergic vulnerability. Recent findings highlight viral infections-particularly SARS-CoV-2-as potential triggers or amplifiers of PD pathogenesis, raising concerns about long-term neurological sequelae following pandemics. Beyond individual toxins, the exposome concept underscores the lifelong interplay of physical, chemical, and social exposures in shaping disease risk. Climate-related changes, including increased air pollution and wildfire frequency, further compound these risks, suggesting a systemic dimension to PD etiology. Understanding these complex interactions is essential for developing preventive strategies, refining experimental models, and informing public health policies aimed at mitigating environmental contributions to neurodegeneration. This multifactorial perspective offers a foundation for future research targeting modifiable risk factors and resilience mechanisms in PD. Parkinson’s disease (PD) is a brain disorder that affects movement and is becoming more common worldwide. While aging and genetics play a role, research shows that environmental factors—such as pesticides, air pollution, industrial chemicals, and even certain infections—may also increase the risk of developing PD. This article explains how these factors can damage brain cells over time. For example, pesticides and solvents can harm the parts of the brain that control movement. Air pollution and heavy metals may also contribute to brain inflammation and stress. Infections like influenza and COVID-19 could act as “triggers,” making the brain more vulnerable to damage later in life. Scientists call this the “multiple-hit” theory, meaning PD often results from a combination of aging, genes, and environmental exposures rather than a single cause. The review also introduces the concept of the “exposome,” which looks at all the things we are exposed to throughout life—chemicals, air quality, diet, and even stress—and how they interact with our biology. Understanding these links can help researchers find ways to prevent PD, improve treatments, and guide public health policies. In short, Parkinson’s disease is not just about getting older or having certain genes. It may also be influenced by what we breathe, eat, and encounter in our environment. By studying these factors, we can work toward reducing risks and protecting brain health.
Multiple sclerosis (MS) is a common central nervous system disease among young adults worldwide and Finland is one of the high-risk MS regions in Europe. Fatigue affects around 80% of individuals with MS, with prevalence rising to 95% as the disease progresses. Fatigue significantly limits daily activities and is associated with poorer employment outcomes and reduced quality of life. The objective of this qualitative study is to explore the lived experiences of individuals with MS and conceptions of MS-related fatigue among physiotherapists. This qualitative study is part of a larger research project entitled 'Building conceptualisation and understanding of momentary fatigue and activity-related fatigability in daily life for people with multiple sclerosis' (EMA-FAMS), consisting of several studies conducted from 2024 to 2028. For this qualitative study, 10 individuals with relapsing-remitting MS will be interviewed using a phenomenological approach to collect their lived experiences of fatigue. Additionally, 15 physiotherapists with experience in MS rehabilitation will be interviewed using a phenomenographic approach to explore their conceptions of MS-related fatigue. All interviews will be conducted remotely during 2025-2026. Interview data will be analysed in two phases using interpretative phenomenological analysis (IPA) and phenomenographic analysis methods. The EMA-FAMS study project has obtained ethical approval from the Regional Medical Research Ethics Committee of the Helsinki University Hospital District (HUS/10011/2024), and all the participants will provide written consent. Findings of this study will be shared through peer-reviewed articles, at academic conferences and with public healthcare and healthcare professionals.
Ischemic stroke (IS), a predominant cerebrovascular disorder contributing to global disability and mortality, characterizes by a complex, multi-tiered cascade of pathological processes. As the primary innate immune cells within the central nervous system (CNS), microglia exhibit dual functional characteristics following ischemic injury, switching dynamically between pro-inflammatory detrimental phenotypes and anti-inflammatory reparative phenotypes in response to temporal progression, cellular phenotypic transformation, and changes in the local microenvironment. Consequently, therapeutic strategies targeting microglia have garnered considerable research interest, challenging the traditional neuron-centric therapeutic approaches. Microglia display a wide range of phenotypes, and the traditional M1/M2 classification is overly simplistic, failing to capture the full spectrum of their functional diversity. In contrast, single-cell RNA sequencing (scRNA-seq) technology has surpassed the limitations of bulk sequencing, providing a robust tool for elucidating microglial heterogeneity. Recent studies utilizing animal models of stroke have identified several subsets distinct from the conventional M1/M2-like subsets, including but no limited to ischemic stroke-associated microglia (ISAM), Prdx1 +SAM, Spp1 +microglia and SAM-foamy. The mechanisms underlying microglial heterogeneity encompass innate programming influenced by genetic background, dynamic remodeling of epigenetic modifications, metabolic reprogramming in response to extrinsic microenvironmental stress, and intercellular interaction networks. This review systematically examines, from the perspective of scRNA-seq, the biological functions of MG, the heterogeneity observed throughout their CNS life cycle development and regional homeostasis, the characteristics and regulatory mechanisms of heterogeneous microglial subpopulations following ischemic stroke, and potential therapeutic strategies and associated challenges. The aim is to provide a reference for the development of precise therapeutic strategies for IS. Ischemic stroke causes damage to brain tissue, and microglia play a crucial role in the process of injury repair. Previous studies suggested that these cells have a single function, but the emergence of single cell sequencing technology has enabled us to see that they actually belong to a “large family”. This family consists of various subtypes with different functions, and they are distributed in different locations in the brain tissue after stroke and have different marker genes. Some subtypes can clear damaged tissues and protect nerves, while others will aggravate inflammation and expand the damage area. Studying the characteristics and mechanism of action of these subtypes can help us find precise regulatory methods. For example, specifically activating protective subtypes and inhibiting harmful subtypes can provide new treatment options for ischemic stroke. This research has opened a personalized path for stroke treatment and is expected to benefit more patients.
Early detection of Parkinson's disease (PD) through speech analysis offers significant clinical advantages, yet no validated tools exist for Arabic-speaking populations, representing a critical gap in global healthcare. Previous studies have relied on limited machine learning (ML) classifiers and voice attributes, which may introduce bias and hinder effective technique discovery. To address this, we developed an optimal PD prediction pipeline by testing multiple ML classifiers and feature extraction methods. We created the first Arabic PD speech dataset, comprising 40 subjects (17 with PD and 23 controls), and validated our methodology on an independent Spanish cohort of 100 subjects. Feature extraction included traditional, audio-to-text, and deep voice features from a pre-trained Whisper model. We employed feature selection and dimensionality reduction techniques to refine the dataset dimensions. Final features were assessed using twelve classifiers with leave-one-out and k-fold cross-validation for robust performance evaluation. Shapley additive explanations (SHAP) were utilized to determine feature importance as vocal biomarkers. Linear Discriminant Analysis achieved optimal performance with 90% accuracy, precision, recall, and F1-score using leave-one-out cross-validation. Linear Support Vector Classification also performed well, achieving 87.7% precision and 87.5% recall. When tested on the independent Spanish dataset, our methodology attained 83% accuracy, confirming cross-linguistic generalizability. SHAP analysis indicated that audio-to-text features provide contextual insights on fluency and coherence, while traditional features effectively capture acoustic variations. This study establishes the first validated Arabic PD speech classification system and demonstrates its universal applicability, laying the groundwork for global speech-based PD screening. Parkinson’s disease (PD) affects how a person speaks, often causing changes in voice quality and fluency that are hard for the human ear to measure in early stages. While technology can analyze these changes to help doctors diagnose the disease early, most of this research has been done in English or European languages. This has created a gap in care for over 400 million Arabic speakers worldwide. In this study, we developed the first validated system specifically designed to detect Parkinson’s disease from Arabic speech. We recorded speech samples from individuals with Parkinson’s and healthy volunteers. We then used advanced computer programs (machine learning) to identify patterns in their voices. To make sure our tool works for everyone and not just one group, we also tested it on a different group of people speaking Spanish. Our system was able to identify Parkinson’s with 90% accuracy in the Arabic group and 83% accuracy in the Spanish group. This research is important because it shows that speech-based tools can work across different languages and cultures. Because this tool can run on simple technology like a smartphone, it could make Parkinson’s screening much more accessible and affordable, especially in areas where specialized doctors are hard to find. This is a major step toward using technology to provide fairer healthcare for people with neurological conditions globally.
CCHS is a rare disorder caused by PHOX2B gene variants. While CCHS hallmarks are hypoventilation and respiratory control dysfunction necessitating lifelong artificial ventilatory support, affected individuals also experience widespread, but less studied, autonomic nervous system (ANS) dysregulation. PHOX2B variants may be divided into moderate and severe groups based upon molecular and in silico data. The International CCHS Registry is a secure repository for longitudinal data from individuals with a PHOX2B variant-confirmed diagnosis, including information on seven systems served by the ANS (cardiovascular, gastrointestinal, neurological, ophthalmologic, renal/urinary, respiratory, sudomotor). Our objective was to analyze patient-reported symptoms (PRS) across all ANS-served systems and determine their relationship with PHOX2B variant severity. We hypothesized an increase in PRS in all organ systems in individuals with severe variants. This study analyzed completed initial surveys. Descriptive statistics were generated for all PRS, and by PHOX2B variant groups, with statistical comparison using the Wilcoxon Rank-Sum and Fisher's exact tests with Benjamini-Hochberg correction. Analysis of 148 surveys confirmed broad, multi-system ANS dysfunction in CCHS. Those with severe PHOX2B variants were more likely to report cardiovascular, gastrointestinal, neurological, respiratory, and ophthalmological system dysfunction compared to individuals with moderate variants. Individuals with severe PHOX2B variants reported significantly more symptoms in 6/7 organ systems than those with moderate variants. The individual-reported impact of CCHS varies by both PHOX2B variant severity and the ANS organ system/symptom manifestations. Beyond the traditional clinical focus on cardiorespiratory dysfunction, these results highlight other ANS-related systems that are critical for comprehensive clinical management and future therapeutic trial design.
Despite the estimated 776 million coronavirus disease 2019 (COVID-19) cases globally, little is known about its impact on immune-mediated neurological disorders such as neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody disorder (MOGAD). Scattered case reports, and reviews address this association, but none have collectively examined the impact of COVID-19 infection or vaccination on established and new-onset NMOSD and MOGAD. Reviewing all published reports of COVID-19 infection and vaccination in NMOSD and MOGAD from December 2019 to October 2024, this report examined the effects of infection and vaccination on patients with established disease and the occurrence of new-onset NMOSD and MOGAD. Outcomes associated with COVID-19 infection in NMOSD and MOGAD patients revealed similar hospitalization rates but a notable difference in deaths in NMOSD patients treated with rituximab. Following COVID-19 infection, twice as many patients developed new-onset MOGAD compared to NMOSD, with a similar larger number of patients who developed MOGAD than NMOSD post-COVID-19 vaccination. While the heavy female predominance in NMOSD is well-established, a greater ratio of male to female patients developed MOGAD post-infection and post-vaccination. Clinicians should closely monitor NMOSD patients with COVID-19 infection, particularly those receiving B-cell depleting therapies, among whom mortality was more frequently reported. The rise in NMOSD and MOGAD following COVID-19 infection and vaccination cases warrants further investigation of the underlying immunological mechanisms. Molecular mimicry and a bystander immune-mediated injury likely play a greater role in central nervous system damage than does direct viral injury.