Breath analysis of epilepsy patients using valproic acid

Valproic acid (VPA) is a widely used antiepileptic drug, but it can cause high blood ammonia levels (hyperammonemia). If not used, epileptic activity increases and the patient's health deteriorates. A two-way follow-up plan has been designed to monitor the patient's medication use and side effects. Breath test samples were collected from 15 healthy control individuals, 21 epilepsy patients receiving VPA treatment, and 25 participants using other medications using the Bosch BME688 metal-oxide sensor array and a machine learning-based "electronic nose" approach. The volatile organic compound (VOC) profiles obtained from the participants' breath samples were processed using an artificial intelligence algorithm to distinguish the group of patients using VPA from the healthy controls. The model demonstrated high discriminative power, achieving 83% classification accuracy and an F1 score of 0.76 through cross-validation. Additionally, the side effect of the medication, elevated blood ammonia levels, was measured using the ECSense electrochemical sensor in 15 healthy controls and 10 epilepsy patients receiving VPA treatment, along with blood VPA, blood ammonia, and breath ammonia concentrations. Statistical analyses revealed that blood ammonia levels in VPA-treated patients (median ~80 μg/dL) were significantly higher than those observed in healthy controls (median ~30 μg/dL) (p<0.001). Similarly, breath ammonia levels were also significantly higher in the VPA group compared to controls (p<0.001). An important finding was the strong positive correlation (r=+0.75) between breath and blood ammonia levels. The findings of this pilot study suggest that breath analysis can serve as a non-invasive method for monitoring the use and metabolic effects of VPA treatment.