HRV features as potential biomarkers for auxiliary diagnosis in epilepsy

Epilepsy affects around 70 million people worldwide, and diagnosis is often difficult and delayed, exposing patients to avoidable morbidity and psychosocial burden. Heart rate variability (HRV) is a non-invasive marker of autonomic nervous system function that may be altered in epilepsy and may support clinical decision-making. In this single-center case-control study, we recorded short-term HRV during a standardized cardiovascular autonomic reflex test including supine resting, deep-breathing and three challenges (active standing, Valsalva manoeuvre and sustained handgrip) in 200 adults with epilepsy and 200 age- and sex-matched healthy controls. Patients with epilepsy showed consistently lower HRV than controls. Using HRV and demographic features, we developed logistic regression models to distinguish epilepsy from health in an independent test set. A model integrating rest and sustained handgrip achieved the highest performance, although still only moderate (area under the curve 0.68; sensitivity 0.821; specificity 0.484). Standardized multi-paradigm HRV assessment may therefore provide a feasible, low-cost adjunct to support, but not replace, conventional diagnostic evaluation. However, the single-center design, relatively short recordings and inclusion of only healthy controls limit generalizability, and larger multicenter studies including patients with paroxysmal conditions that mimic epilepsy are needed to determine clinical utility.