Selective reduction of thalamic glutathione in migraine in the absence of detectable N-acetylaspartate alterations
Abstract
Background: Oxidative stress has been implicated in migraine pathophysiology, but direct evidence of brain antioxidant alterations and their relationship to neuronal integrity remains limited.
Methods: We conducted a cross-sectional proton magnetic resonance spectroscopy (1H-MRS) study measuring seven metabolites in a single thalamic voxel of 131 participants (left or right, selected for spectral quality): 36 healthy controls, 46 migraines without aura, 17 migraines with aura, and 32 tension-type headache patients.
Results: Glutathione (GSH) was the only metabolite showing significant group differences (Welch's F = 31.74, p 2 = 0.432). Thalamic GSH was reduced in migraine without aura (1.76 ± 0.16) and migraine with aura (1.70 ± 0.13) compared to healthy controls (2.07 ± 0.20), with large effect sizes (Cohen's d = 1.70 and 2.14, respectively). N-acetylaspartate (NAA), a marker of neuronal integrity, showed no group differences (p = 0.74). Equivalence testing showed that the GSH-NAA correlation was statistically equivalent to zero within predefined bounds (TOST p = 0.015), indicating that GSH reduction occurred in the absence of a detectable linear association with NAA in this sample. GSH demonstrated good diagnostic performance (AUC = 0.895, 95% CI 0.821-0.952; sensitivity 93.7%; specificity 69.4%), validated by permutation testing (p = 0.001).
Conclusions: These findings indicate selective thalamic GSH reduction in migraine in the absence of detectable NAA alterations.…
How strong is the evidence?
Evidence Hub reads this as a cross-sectional, done in people. Its evidence level is 4 of 5 (Low · observational). Observational designs can show an association but not prove cause. Reported size: 131 participants or records.
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