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Keywords:

  • glutamate;
  • glutamine;
  • migraine;
  • pathophysiology;
  • proton magnetic resonance spectroscopy

Background

Glutamate (Glu) and glutamine (Gln) are strongly compartmentalized (in neurons for Glu and in astrocytes for Gln). The visual cortex is the brain region with a higher neuron/astrocyte ratio (the highest neuronal density and the relatively lowest density of astrocytes). Elevations in extracellular Glu or potassium above certain thresholds are likely candidates to be the final common steps in the multiple distinct processes that can lead to cortical spreading depression. Astrocytes play a key role in this phenomenon, by acting as a sink for extracellular Glu and potassium, as well as generally acting as a buffer for the ionic and neurochemical changes that initiate and propagate cortical spreading depression.

Objective

The purpose of this study was to quantify Glu and Gln to generate Glu/Gln ratios in women with migraine during the interictal state compared with healthy control women.

Methods

Twenty-seven patients with migraine (8 with aura and 19 without aura) and 19 matched healthy controls were included in the study. We performed proton magnetic resonance spectroscopy in the anterior paracingulate cortex and occipital cortex (OC). Spectral analysis was performed by LCModel, allowing a separation of Glu and Gln using a 3T machine.

Results

The main result was a significantly higher Glu/Gln ratio in the OC of migraine patients compared with healthy control subjects (4.87 for migraineurs [standard deviation (SD) = 2.74] and 3.42 for controls [SD = 1.52], P = .042). We also observed higher Glu levels (6.98 for migraineurs [SD = 0.85] and 6.22 for controls [SD = 0.97], P = .007) and Glu/creatine + phosphocreatine ratio (1.18 for migraineurs [SD = 0.18] and 1.00 for controls [SD = 0.16], P = .001) in anterior paracingulate cortex in migraine patients but saw no differences in Glu/Gln ratio (2.79 for migraineurs [SD = 1.11] and 2.63 for controls [SD = 1.61], P = .68).

Conclusion

These findings are consistent with glutamatergic differences in migraine patients during the interictal period compared with healthy controls. We hypothesize that an increased Glu/Gln ratio could arise from neuronal–glial coupling of glutamatergic metabolism differences or an increased neuron/astrocyte ratio in the OC.