Enhanced activity of the glutamatergic system has been linked to migraine pathophysiology. The present study aimed to assess the involvement of the glutamatergic system in the onset of attacks. We... Show moreEnhanced activity of the glutamatergic system has been linked to migraine pathophysiology. The present study aimed to assess the involvement of the glutamatergic system in the onset of attacks. We provoked attacks by infusion of glyceryl trinitrate (GTN; 0.5 mu g/kg/min over 20 min) in 24 female episodic migraineurs without aura and 13 female age-matched healthy controls. Over the course of a single day participants were scanned three times at fixed time slots (baseline before GTN infusion, 90 min and 270 min after start of GTN infusion). Single volume proton magnetic resonance spectra (H-1-MRS) were acquired at 7 Tesla from a volume of interest (VOI, 2x2x3 cm) in the visual cortex. We assessed the concentrations of glutamate, its major precursor glutamine, and its product gamma-aminobutyric acid (GABA) over the course of a provoked attack. The preictal state was defined as the period after GTN infusion until the migraine-like headache started, independent of possible experienced premonitory symptoms, and the ictal state was defined as the period with provoked migraine-like headache. Data were analyzed using a linear mixed-effect model for repeated measures. Glutamate and glutamine levels did not change from interictal to the preictal and ictal state. GABA levels increased from interictal towards the preictal state for migraine patients compared with healthy controls. We conclude that high resolution 7T MRS is able to show changes in the glutamatergic system towards a triggered migraine attack, by revealing an increased GABA concentration associated with the onset of a migraine attack. Show less
Spontaneous and pharmacologically provoked migraine attacks are frequently preceded by nonheadache symptoms called premonitory symptoms. Here, we systematically evaluated premonitory symptoms in... Show moreSpontaneous and pharmacologically provoked migraine attacks are frequently preceded by nonheadache symptoms called premonitory symptoms. Here, we systematically evaluated premonitory symptoms in migraine patients and healthy controls after glyceryl trinitrate (GTN) infusion. In women with migraine without aura (n = 34) and age-matched female controls (n = 24), we conducted systematically a semistructured interview assessing 21 possible premonitory symptoms every 15 minutes in the 5 hours after GTN infusion (0.5 mu g/kg/min over 20 minutes). Migraine-like headaches occurred in 28/34 (82.4%) migraineurs (GTN responders). After GTN, 26/28 (92.9%) responders, 6/6 (100%) nonresponders, and 13/24 (54.2%) controls reported at least one possible premonitory symptom. Concentration difficulties (P= 0.011), yawning (P= 0.009), nausea (P= 0.028), and photophobia (P= 0.001) were more frequently reported by those migraineurs who developed a migraine-like attack vs healthy controls. Importantly, concentration difficulties were exclusively reported by those who developed a migraine-like attack. Thus, our findings support the view that GTN is able to provoke the naturally occurring premonitory symptoms and show that yawning, nausea, photophobia, and concentration difficulties are most specific for an impending GTN-induced migraine-like headache. We suggest that these symptoms may also be helpful as early warning signals in clinical practice with concentration difficulties exclusively reported by those who develop a migraine-like attack. Show less
