Longitudinal changes in neurometabolites in pediatric migraine across child development: a pilot study

Migraine severely impacts quality of life in children and adolescents and has been identified as the most important cause of neurological disability in youth. There is evidence that an imbalance between brain excitation (glutamate) and inhibition (GABA) is one of the driving factors behind migraine attacks. During adolescence, changes to glutamatergic and GABAergic neurons occur. It is therefore perhaps unsurprising that adolescence is also a transitory time for migraine, with changes in incidence and associated symptoms. However, there is a lack of research into interactions between brain chemistry changes and progression of migraine during the adolescent period. In this longitudinal study, magnetic resonance spectroscopy (MRS) was used to measure metabolite levels in the thalamus, sensorimotor cortex and visual cortex over two sessions (on average 3 years apart) in participants ages 7-18y. We show that a decrease in thalamic GABA levels over time is related to new onset migraine in previously unaffected adolescents (t(41.4) = 2.79, p = 0.008) and increased disease burden in those who previously experienced migraine (b=-0.01, SE = 0.003, p < 0.001). This provides new evidence for a role of thalamic GABA early in migraine onset and progression, and a potential target for new treatments.