Regional cerebral perfusion during the premonitory phase of triggered migraine: A double‐blind randomized placebo‐controlled functional imaging study using pseudo‐continuous arterial spin labeling

Objective To identify changes in regional cerebral blood flow (CBF) associated with premonitory symptoms (PS) of nitroglycerin (NTG)‐triggered migraine attacks. Background PS could provide insights into attack initiation and alterations in neuronal function prior to headache onset. Methods We undertook a functional imaging study using a double‐blind placebo‐controlled randomized approach in patients with migraine who spontaneously experienced PS, and in whom PS and migraine‐like headache could be induced by administration of NTG. All study visits took place in a dedicated clinical research facility housing a monitoring area with clinical beds next to a 3Tesla magnetic resonance imaging scanner. Fifty‐three patients with migraine were enrolled; imaging on at least one triggered visit was obtained from 25 patients, with 21 patients completing the entire imaging protocol including a placebo visit. Whole brain CBF maps were acquired using 3D pseudo‐continuous arterial spin labeling (3D pCASL). Results The primary outcome was that patients with migraine not taking preventive treatment (n = 12) displayed significant increases in CBF in anterior cingulate cortex, caudate, midbrain, lentiform, amygdala and hippocampus (p