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BACKGROUND AND PURPOSE: Prior observational studies have suggested a strong correlation between sarcopenia and stroke, but the causal link between them remains uncertain. This study aims to investigate the associations between genetically predicted sarcopenia-related traits and stroke using a two-step Mendelian randomization (MR) approach. METHODS: Genome-wide association study (GWAS) summary data for sarcopenia-related traits were acquired from the UK Biobank. Genetic associations for ischemic stroke (IS) and its subtypes were selected from the MEGASTROKE consortium comprising European ancestry participants. GWAS summary data for cerebral hemorrhage were obtained from the FinnGen consortium, including intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH). MR estimates were calculated using the inverse-variance weighted (IVW) method. The robustness of results was assessed for heterogeneity and pleiotropy of individual single nucleotide polymorphisms (SNPs). RESULTS: Higher appendicular lean mass (ALM) exhibited a potential causal association with a reduced incidence of large artery atherosclerosis (LAA) (odds ratio [OR] = 0.81, 95% confidence interval [CI]:0.71-0.93; P = 0.003) and small vessel disease (SVD) (OR = 0.83, 95% CI:0.74-0.94; P = 0.002). The associations of ALM with IS and ICH were compromised after adjusting for body fat and physical activity with multivariable MR. Two-step MR mediation analysis explored 33 candidate mediators, among which hypertension and SBP accounted for more than 10% of the mediation proportion in the relationship between ALM and stroke and its subtypes. CONCLUSION: Our research findings indicate that lower ALM is associated with a increased risk of stroke . It is necessary to explore the specific protective mechanisms of higher ALM for preventing stroke occurrence.
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OBJECTIVE: This study aims to explore the frequency and influencing factors of asymptomatic spinal lesions (ASLs) and their impact on subsequent relapses in patients with AQP4-IgG-positive NMOSD (AQP4-NMOSD) in a real-world setting. METHODS: We retrospectively reviewed clinical information and spinal MRI data from AQP4-NMOSD patients who had at least one spinal cord MRI during their follow-ups. Kaplan-Meier curves and Cox proportional hazards models were employed to ascertain potential predictors of remission ASLs and to investigate factors associated with subsequent relapses. RESULTS: In this study, we included 129 patients with AQP4-NMOSD and reviewed 173 spinal MRIs during attacks and 89 spinal MRIs during remission. Among these, 6 ASLs (3.5%) were identified during acute attacks, while 8 ASLs (9%) were found during remission. Remission ASLs were linked to the use of immunosuppressive agents, particularly conventional ones, whereas no patients using rituximab developed ASLs (p = 0.005). Kaplan-Meier curve analysis indicated that patients with ASLs had a significantly higher relapse risk (HR = 4.658, 95% CI: 1.519-14.285, p = 0.007) compared to those without. Additionally, the use of mycophenolate mofetil (HR = 0.027, 95% CI: 0.003-0.260, p = 0.002) and rituximab (HR = 0.035, 95% CI: 0.006-0.203, p < 0.001) significantly reduced the relapse risk. However, after accounting for other factors, the presence of ASLs did not exhibit a significant impact on subsequent relapses (HR = 2.297, 95% CI: 0.652-8.085, p = 0.195). INTERPRETATION: ASLs may be observed in patients with AQP4-NMOSD. The presence of ASLs may signify an underlying inflammatory activity due to insufficient immunotherapy. The administration of immunosuppressive agents plays a key role in the presence of remission ASLs and the likelihood of subsequent relapses.