Long-term neurological outcomes of burn injury and the potential mediating role of plasma metabolite profiles and brain structural alterations: A prospective cohort study.

BACKGROUND

Burn injury is a common traumatic event that can lead to long-term neurological sequelae, yet the underlying mechanisms remain poorly understood. We aimed to investigate the associations between burn injury and long-term neurological outcomes, and to examine the potential mediating roles of plasma metabolite profiles and brain structural alterations.

METHODS

We conducted a prospective cohort study using data from UK Biobank. Neurological outcomes-including stroke, limb weakness, hearing loss, cognitive decline, depression, anxiety, and insomnia-were assessed. Plasma metabolomics were profiled using NMR spectroscopy, and brain structural metrics were derived from MRI in a subset of participants. Mediation analyses evaluated whether metabolite or brain structural changes explained the associations between burn injury and neurological outcomes. An updated review was performed to contextualize our findings based on our previous study.

RESULTS

Burn injury was associated with significantly increased risks of stroke (hazard ratio [HR]: 1.67; 95% confidence interval [CI]: 1.42-1.97), limb weakness (HR: 1.45; 95% CI: 1.16-1.81), hearing loss (HR: 1.48; 95% CI: 1.20-1.83), cognitive decline (HR: 1.42; 95% CI: 1.11-1.80), anxiety (HR: 1.33; 95% CI: 1.10-1.59), and insomnia (HR: 3.60; 95% CI: 2.69-4.80). Plasma metabolite profiling revealed persistent alterations in lipoprotein subclasses, fatty acid composition, and amino acid metabolites, several of which partially mediated associations with stroke and limb weakness. Burn injury was also linked to widespread white matter microstructural abnormalities and reduced cortical gray matter volume; however, brain structural changes did not mediate the neurological risks.

CONCLUSIONS

Burn injury is associated with elevated long-term neurological risks, accompanied by persistent metabolic and neurobiological alterations. Metabolic dysregulation partially mediates neurovascular outcomes, while structural brain changes may reflect parallel or secondary processes.