History of migraine with aura and cortical spreading depression from 1941 and onwards

Abstract

Several personal descriptions of migraine with aura from 1870 onwards reported a slow, gradual progression of symptoms. Lashley in 1941 meticulously chartered his own auras and concluded that the symptomatology reflected a cortical process progressing with a speed of 3 mm/min across the primary visual cortex. Leão described cortical spreading depression (CSD) in rabbits in 1944 and noticed its similarity to the migraine aura. Despite these scattered pieces of evidence, the prevailing theory was that the migraine aura was caused by a vasospasm and cortical ischaemia. The advent of a technique for measurements of regional cerebral blood flow (rCBF) in 1974 made it possible to detect spreading oligaemia during migraine aura. Between 1981 and 1990 a series of studies of rCBF during migraine attacks showed reduced brain blood flow posteriorly spreading slowly and contiguously anteriorly and crossing borders of supply of major cerebral arteries. These observations refuted the ischaemic hypothesis. The human studies showed initial hyperaemia followed by prolonged hypoperfusion. The relation between aura and CSD was known to cause short-lasting, and therefore not obvious vasodilation and it was considerably strengthened by the demonstration of a long-lasting oligaemia in rats in the wake of CSD. In the primates CSD is not easily elicited, but it has in recent years been clearly demonstrated in patients with brain trauma and stroke. Finally, mutations for familial hemiplegic migraine have been expressed in mice and lower the threshold for CSD. The seminal papers on rCBF and CSD published in the 1980s caused a dramatic shift in our concepts of migraine aura. They moved attention from ischaemia to CSD and thereby to the brain itself, and paved the way for subsequent discoveries of brainstem mechanisms.

An Arterial Spin Labeling MRI Perfusion Study of Migraine without Aura Attacks

“…The visual aura has since then been consistently associated with a posteroanterior spreading wave of initial transient hyperperfusion followed by sustained hypoperfusion (CBF variation of −10 to −35%) (2) demonstrated in human subjects by different techniques [ 133 Xe, SPECT, PET, and perfusion weighted imaging (PWI)-MRI (3)]. It is nowadays widely accepted that CBF changes occurring during the aura are associated with cortical spreading depression-like phenomena (4). …”

Lyapunov analysis of the spatially discrete-continuous system dynamics

“…As an example we consider a simplified model, which describes dynamical mechanisms underlying the extreme physiological behaviors in brain cortex, such as spreading depression [51], migraine waves [52], and peri-infarct depolarization waves [53].…”

Migraine in the era of precision medicine

“…CSD is a self-propagating wave of neuronal and glial depolarization (22), which is identified as the reason of the neurological aura symptoms (23). CSD is initiated by massive increases in extracellular potassium ion concentration and excitatory glutamate.…”