Retrospective analysis of existing LC-MS/MS raw data from migraine patients: Investigation of changes in amino acid derivatives (arginine, histidine, 1-methylhistidine, and 3-methylhistidine) associated with BoNT-a treatment

Migraine is a chronic neurovascular disorder that markedly impairs quality of life. Although the clinical efficacy of botulinum toxin type A (BoNT-A) is well established, accompanying metabolic changes remain insufficiently characterized. In this retrospective study, coded serum data from 30 patients with chronic migraine and 30 age- and sex-matched healthy controls were reanalyzed. In the migraine cohort, pre-treatment values were compared with measurements obtained 1 month after BoNT-A, and clinical response was assessed using the Visual Analog Scale (VAS) and monthly attack frequency. After BoNT-A, VAS decreased from 8.17±1.29 to 1.63±1.35 and monthly attacks from 10.63±5.27 to 1.07±1.05. In parallel, histidine increased from 51.66±10.19 to 60.87±5.90 µmol/L and 3-methylhistidine decreased from 0.97±0.43 to 0.70±0.18 µmol/L, while arginine showed no significant change. In subgroup analyses, men exhibited a larger VAS reduction than women, whereas smoking status was not associated with clinical or biochemical response. Change in histidine was not correlated with VAS improvement; however, baseline histidine independently predicted VAS change in robust multiple linear regression. In ROC analysis, histidine (AUC=0.789) and 3-methylhistidine (AUC=0.714) demonstrated moderate-to-good discrimination between chronic migraine and controls. Keywords: migraine; botulinum toxin type A; LC–MS/MS; amino acid metabolism; histidine; 3-methylhistidine; retrospective analysis