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Objective: Although metabolic abnormalities are implicated in the etiology of neurodegenerative diseases, their role in the development of amyotrophic lateral sclerosis (ALS) remains a subject of controversy. We aimed to identify the association between metabolic syndrome (MetS) and the risk of ALS. Methods: This study included 395,987 participants from the UK Biobank to investigate the relationship between MetS and ALS. Cox regression model was used to estimate hazard ratios (HR). Stratified analyses were performed based on gender, body mass index (BMI), smoking status, and education level. Mediation analysis was conducted to explore potential mechanisms. Results: In this study, a total of 539 cases of ALS were recorded after a median follow‐up of 13.7 years. Patients with MetS (defined harmonized) had a higher risk of developing ALS after adjusting for confounding factors (HR: 1.50, 95% CI: 1.19–1.89). Specifically, hypertension and high triglycerides were linked to a higher risk of ALS (HR: 1.53, 95% CI: 1.19–1.95; HR: 1.31, 95% CI: 1.06–1.61, respectively). Moreover, the quantity of metabolic abnormalities showed significant results. Stratified analysis revealed that these associations are particularly significant in individuals with a BMI <25. These findings remained stable after sensitivity analysis. Notably, mediation analysis identified potential metabolites and metabolomic mediators, including alkaline phosphatase, cystatin C, γ‐glutamyl transferase, saturated fatty acids to total fatty acids percentage, and omega‐6 fatty acids to omega‐3 fatty acids ratio. Interpretation: MetS exhibits a robust association with an increased susceptibility to ALS, particularly in individuals with a lower BMI. Furthermore, metabolites and metabolomics, as potential mediators, provide invaluable insights into the intricate biological mechanisms. ANN NEUROL 2024;96:788–801 [ABSTRACT FROM AUTHOR]

Background: Diabetic peripheral neuropathy (DPN) constitutes a debilitating complication associated with diabetes. Although, the past decade has seen rapid developments in understanding the complex etiology of DPN, there are no approved therapies that can halt the development of DPN, or target the damaged nerve. Therefore, clarifying the pathogenesis of DPN and finding effective treatment are the crucial issues for the clinical management of DPN. Aims: This review is aiming to summary the current knowledge on the pathogenesis of DPN, especially the mechanism and application of inflammatory response. Methods: We systematically summarized the latest studies on the pathogenesis and therapeutic strategies of diabetic neuropathy in PubMed. Results: In this seminal review, the underappreciated role of immune activation in the progression of DPN is scrutinized. Novel insights into the inflammatory regulatory mechanisms of DPN have been unearthed, illuminating potential therapeutic strategies of notable clinical significance. Additionally, a nuanced examination of DPN's complex etiology, including aberrations in glycemic control and insulin signaling pathways, is presented. Crucially, an emphasis has been placed on translating these novel understandings into tangible clinical interventions to ameliorate patient outcomes. Conclusions: This review is distinguished by synthesizing cutting‐edge mechanisms linking inflammation to DPN and identifying innovative, inflammation‐targeted therapeutic approaches. [ABSTRACT FROM AUTHOR]

Background Methods Results Interpretation Previous studies have observed liver abnormalities in amyotrophic lateral sclerosis (ALS) patients. This study aimed to investigate whether early signs of liver disease, measured by magnetic resonance imaging‐derived iron‐corrected T1‐mapping (cT1), are risk factors for developing ALS.cT1 and proton density fat fraction were measured and automatically analyzed using LiverMultiScan® software. The Fibrosis‐4 index was calculated using an established formula based on age and blood markers. Cox proportional hazard models were used to examine the relationship between liver disease, liver biomarkers, and incident ALS.In a cohort of 533,707 individuals from UK Biobank, 24 ALS cases were identified among 28,328 participants with liver disease during the follow‐up period. Among a total of 33,959 individuals with complete liver imaging data, 15 incident ALS cases were observed during a median follow‐up period of 5.6 years. Individuals with liver disease had a higher risk of developing ALS, with an adjusted hazard ratio of 7.35 (95% CI 4.47–12.09; p < 0.001). An increase in cT1 was also associated with a higher risk of ALS. After adjusting for age, sex, Townsend deprivation index, smoking status, alcohol intake frequency, body mass index, proton density fat fraction, Fibrosis‐4, and metabolic syndrome, an increase in cT1 remained significantly associated with a higher risk of ALS, with an adjusted hazard ratio of 3.15 (95% CI 1.79–5.55) per 1‐SD increase. Sensitivity analyses confirmed these robust results.Liver disease activity, indicated by cT1, increases the risk of developing ALS, independent of metabolic syndrome, liver fat, or fibrosis. ANN NEUROL 2024 [ABSTRACT FROM AUTHOR]

Background and Aims Methods Results Interpretation Little is known about the ability of serological biomarkers to monitor clinical outcomes in patients with Guillain‐Barré syndrome (GBS). The objective of this study was to determine the associations of liver function, easily available and convenient biomarkers, with the clinical course and outcome of severe GBS in patients.A prospective data collection was conducted in a cohort of 343 GBS patients from multi‐centers between September 2019 and December 2023. Serum samples were obtained at four‐time points for mechanical ventilation (MV) patients and two‐time points for non‐MV patients. The primary endpoint was the need for MV during hospitalization, while secondary outcomes included the ability to walk independently and the mortality at 26‐week follow‐up.(i) A total of 208 patients were eligible, of whom 50 required MV with a median (interquartile range) ventilation duration of 15 (8–27) days. (ii) Hypohepatia, as evidenced by reduced total protein (OR 0.913 [95% CI 0.862–0.967]) and albumin (0.775 [0.679–0.884]) 1 week after treatment, along with raised liver enzymes (2.732 [1.007–7.413]), was associated with the risk of MV after adjusting for confounders. (iii) After 26‐week follow‐up, patients with hypohepatia were less likely to regain independent walking and exhibited higher mortality in survival analysis (all log‐rank p < .05). (iv) In a cross‐sectional study spanning up to 4 years of follow‐up, patients with prolonged MV (≥15 days) experienced a longer time to regain independent ambulation than those with shorter MV (167 [46–316] vs. 69 [24–106], p = .036). However, no relationships between liver function and prolonged MV were revealed.Dynamically monitoring hepatic metabolism and promptly adjusting, it can aid the improvement of GBS in patients. [ABSTRACT FROM AUTHOR]