MAGNETIC resonance spectroscopy may reveal attack-related metabolic changes in migraine, but current evidence remains limited and inconsistent.
Magnetic Resonance Spectroscopy in Migraine Attacks
Magnetic resonance spectroscopy offers a noninvasive way to measure brain neurochemicals and metabolites during active migraine attacks, a phase that remains difficult to study in vivo. In a systematic review of ictal-phase magnetic resonance spectroscopy studies, available evidence suggested that migraine attacks may be associated with altered cerebral energy metabolism, particularly in visual cortical and brainstem regions.
The review included eight studies published between 1988 and 2022, comprising five proton magnetic resonance spectroscopy investigations and three phosphorus magnetic resonance spectroscopy studies. Brain regions assessed included the occipital cortex, pons, frontal cortex, basal ganglia, and parieto-occipital areas. However, differences in study design, imaging protocols, brain regions, field strength, and metabolite outcomes prevented quantitative synthesis.
Metabolic Changes Outweigh Neurotransmitter Signals
Across proton magnetic resonance spectroscopy studies, occipital cortex findings included ictal elevations in total choline and total N-acetyl aspartate in individual reports, alongside lower glutathione concentrations. One study focused on the pons found increased total creatine and total N-acetyl aspartate during provoked migraine attacks, while pontine glutamate remained unchanged.
Phosphorus magnetic resonance spectroscopy studies pointed more consistently toward altered cerebral energy metabolism. Reported findings included reduced phosphocreatine-related ratios and increased inorganic phosphate measures during attacks, changes interpreted as possible markers of increased neuronal energy demand.
Notably, ictal glutamate changes were not consistently observed, and evidence for reproducible shifts in excitatory or inhibitory neurotransmission remains weak. This distinction is clinically important because migraine pathophysiology is often framed around cortical excitability, neurotransmitter signaling, and altered sensory processing.
Future Migraine Research Needs Standardized MRS
The evidence base remains small and methodologically heterogeneous. Sample sizes ranged from a single participant to 34 participants with migraine, and some studies drew from overlapping cohorts. Several investigations were cross-sectional, limiting the ability to separate stable migraine traits from attack-specific metabolic changes.
Future studies should prioritize longitudinal ictal and interictal imaging within the same participants, standardized acquisition protocols, correction for multiple comparisons, and careful control for medication effects. More targeted assessment of pain-processing regions, including the anterior cingulate cortex, insula, somatosensory cortex, and thalamus, may also help clarify whether magnetic resonance spectroscopy can identify clinically meaningful migraine biomarkers.
For now, magnetic resonance spectroscopy suggests that migraine attacks involve altered brain energy metabolism, but reliable attack-related metabolic signatures have not yet been established.
Reference
Radutiu DI et al. Magnetic resonance spectroscopy during migraine attacks: A systematic review. Cephalalgia. 2026;46(5):3331024261441576.
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