Reduced thalamic glutathione in migraine: a MEGA-PRESS spectroscopy study

BACKGROUND: Migraine and tension-type headache (TTH) are highly prevalent primary headache disorders lacking objective diagnostic biomarkers. Oxidative stress has been implicated in migraine pathophysiology, with glutathione (GSH) serving as the brain's principal antioxidant. This study investigated whether thalamic GSH levels, measured using optimized MEGA-PRESS spectroscopy, could serve as a candidate biomarker for differentiating migraine from TTH. METHODS: This cross-sectional study enrolled 76 participants: 20 healthy controls (HC), 19 TTH patients, and 37 migraine patients (27 without aura, 10 with aura). Bilateral thalamic GSH was measured using MEGA-PRESS at 3T. Group comparisons employed one-way ANOVA with Tukey HSD post-hoc tests. Sex-stratified analyses were performed. ROC analysis evaluated diagnostic performance. RESULTS: Migraine patients showed significantly reduced thalamic GSH compared to both HC and TTH (left thalamus: F = 30.78, p < 0.001, η² = 0.457). Critically, no difference was found between HC and TTH groups. Sex-stratified analyses showed that GSH reduction was significant in both males and females. Left thalamic GSH showed good diagnostic accuracy for distinguishing migraine from both HC (AUC = 0.897) and TTH (AUC = 0.879). CONCLUSIONS: Thalamic GSH reduction appears to differentiate migraine from TTH in this sample, supporting a distinct role of oxidative stress in migraine pathophysiology. GSH may serve as a candidate biomarker for differentiating migraine from TTH. CLINICAL TRIAL NUMBER: Not applicable.