Although previous research has suggested that a greater body mass index (BMI) may be linked to a higher incidence of ankle–foot sprains, the causal relationship between BMI and these injuries has not been established. This study aims to determine the causal effect of BMI-related features on ankle–foot sprains using a two-sample Mendelian randomization (MR) analysis.

Exposure single-nucleotide polymorphisms were collected from Genetic Investigation of Anthropometric Traits (GIANT Consortium) for BMI, hip circumference (HIP), hip circumference adjusted for BMI (HIP_adjBMI), waist circumference (WC), waist circumference adjusted for BMI (WC_adjBMI), waist-to-hip ratio (WHR), and waist-to-hip ratio adjusted for BMI (WHR_adjBMI), encompassing a study population of more than 200​000 individuals. Furthermore, exposure statistics were gathered from MEC-IEU for body fat percentage (BFP), involving a study population of 454​633 individuals. Additionally, outcome statistics for ankle sprains were identified from FinnGen based on hospital discharge records (9141 cases and 290​508 healthy controls). Random-effect, inverse-variance weighted MR was used as the primary method.

BMI (β ​= ​0.173, p ​= ​0.035), BFP (β ​= ​0.341, p ​= ​9.08 ​× ​10⁻⁶), hip circumference (β ​= ​0.265, p ​= ​0.001), and WC (β ​= ​0.193, p ​= ​0.045) were found to have positive causal relationships with higher risk of ankle–foot sprains, whereas HIP_adjBMI, WC_adjBMI, WHR, and WHR_adjBMI were found to have no such effect. Additionally, no reverse causal effect was found between ankle–foot sprains and BMI or BFP.

A genetic predisposition to higher BMI-related features can lead to a higher risk of ankle–foot sprains, providing new insight into how to prevent ankle–foot sprains in middle-aged and elderly people.

Ankle proprioception deficits have been widely reported in patients with chronic ankle instability (CAI), but their central neuropathological mechanisms have not been fully discussed. So, we aimed to figure out whether the structural and functional features of the cerebellar vermis differed between patients with CAI and healthy controls, and are associated with proprioception deficits in patients.

Twenty-two patients and 25 control individuals were enrolled in a cross-sectional investigation. All participants underwent structural and resting-state functional magnetic resonance imaging scanning to calculate voxel-based morphometry (VBM) and fractional amplitude of low-frequency fluctuation (fALFF) of the vermis. Between-group comparisons of the ankle instability-related subregions of the vermis were performed. Correlation analyses were performed between the outcomes of the surviving subregions and the proprioceptive scores of the ankle inversion discrimination apparatus for landing test.

The subregion of vermis Ⅳ/Ⅴ survived the multiple comparison correction to reveal a lower VBM value in patients than in healthy controls (Cohen's d ​= ​−0.968). The patients also showed significantly higher fALFF (Cohen's d ​= ​0.666) in this subregion. After controlling the demographic features, the proprioceptive scores were significantly correlated with VBM (r ​= ​0.622) and fALFF values (r ​= ​−0.512) in the group of patients.

Patients with CAI have lower gray matter volume and higher activity intensity in the cerebellar vermis than healthy control. The more severe proprioception deficits were significantly associated with the vermal volume and activity, which might be able to facilitate future diagnoses and treatments for CAI.

Lateral ankle sprains (LAS) are associated with corticospinal pathway deficits. Existing evidence is primarily based on cross-sectional investigations and noncausal speculations. This study aims to determine whether maladaptive corticospinal pathway alterations occur pre- and postligament transection in LAS mouse models. Additionally, this study explores whether the alterations are more pronounced in adolescent mice than adults.

Twenty-four 8-week-old adolescent and twenty-four 24-week-old adult mice were randomly assigned to lateral ankle ligament transection or sham surgery. Diffusion-weighted imaging of the corticospinal pathway was performed presurgery and 8 weeks postsurgery. Fractional anisotropy (FA) values, reflecting fiber integrity within the corticospinal subregions of the medulla, pons, midbrain, and cerebrum, were extracted.

Overall, 41 mice completed repeated image acquisition. Before surgery, no significant group effects on FA within the four corticospinal subregions were detected in either adolescent or adult mice. Two months after surgery, the adolescent cohort displayed a significant reduction in FA in the medulla subregion following ankle ligament transection (β-baseline-adjusted ​= ​−0.083, 95% CI, −0.145 to −0.021, p-corrected ​= ​0.048). Conversely, no significant effects of ankle ligament transection on corticospinal FA were observed in the adult cohort.

The maladaptive alterations in the corticospinal tract could be observed in the adolescent LAS mouse model, characterized by reduced fiber integrity in the medulla subregion. While these results are derived from an animal model, they provide a foundation for future investigations into the mechanisms underlying neurological deficits following musculoskeletal injuries.

Ankle-foot sprains are the most common musculoskeletal injuries, which can impair balance and theoretically increase the risk of falls, but still, there is a lack of evidence supporting the direct association between ankle-foot sprains and the future risk of falls.

UK Biobank cohort was utilized to measure the association between ankle-foot sprains and fall risk with covariates adjusted. Then, the two-sample Mendelian randomization (MR) analysis was applied based on the genetically predicated ankle-foot sprains from FinnGen to validate causal relationship. Finally, genetically predicated cerebellar neuroimaging features were used to explore the mediating role of maladaptive neuroplasticity between ankle-foot sprains and falls by two-step MR analyses.

Patients with ankle-foot sprains history exhibited a slightly increased risk of falls than the matched controls before and after adjustment for covariates (odd ratio [OR] ranged from 1.632 to 1.658). Two-sample MR analysis showed that ankle-foot sprains led to a higher risk of falls (OR ​= ​1.036) and a lower fractional anisotropy of superior cerebellar peduncle (SCP) (left, β ​= ​−0.052; right, β ​= ​−0.053). A trend of mediating effect was observed for the fractional anisotropy of right SCP in the causal effects of ankle-foot sprains on falls (β ​= ​0.003).

The history of ankle-foot sprains is associated with a slightly increased risk of falls. These findings improve our understanding of the clinical consequences of ankle-foot sprains in terms of fall risk and suggest the importance of adopting more efficient strategies for managing residual functional deficits after the injuries.