A subgroup of migraineurs experience aura, typically before the onset of head pain, with some of their attacks and there are several lines of evidence that cortical spreading depression is the pathophysiological substrate. In early clinical observations, it was noted that the progression of aura symptoms is consistent with a process transiently compromising cortical function at a speed of about 3 mm per minute [
8]. Leao suggested that cortical spreading depression (CSD), advancing at the identical speed over the cortex, was the electrophysiological correlate of visual aura in humans. By now, the existence of CSD in humans has been proven using electrophysiological methods [
9‐
11] and human imaging studies [
12,
13]. A possible link between CSD and headache has been provided by the observation that CSD can activate trigeminal meningeal afferents [
14], although contradictory data also exist [
15]. Hence, CSD could not only induce aura symptoms, but also explain the head pain in patients with aura. This view is not supported by recent controlled trials which show that tonabersat, a possible gap-junction blocker and inhibitor of CSD [
16], does not prevent migraine headache [
17] but can prevent migraine aura [
18]. It has been suggested that CSD also has a role in migraine without aura but the tonabersat studies suggest this is less likely. Silent aura, the occurrence of CSD confined to regions not clinically eloquent and still activating trigeminal afferents, is a tempting concept when looking for a unifying concept of migraine with and without aura. However, as noted above in the study by Hauge
et al. [
18], tonabersat was ineffective in migraine without aura and, as the drug reduced the frequency of aura attacks, this result clearly challenges the concept of the silent aura [
18]. Moreover, in a recent case series, three patients were described who reported that their auras resolved when migraine preventives were started, while in parallel they experienced a worsening of the frequency of their migrainous headaches [
19]. Finally, the sequence of a migraine attack has probably already been initiated long before the actual onset of CSD and aura. Migraine attacks often start with a typical premonitory phase when patients complain of tiredness, reduced concentration, irritability, yawning and other non-headache symptoms hours to days before the onset of aura and headache [
20,
21]. At this point, many patients can predict the onset of a full-blown migraine attack and the start with non-headache symptoms underlines that migraine is much more than an isolated pain disorder.