Cerebral blood flow and arterial responses in migraine: history and future perspectives

Abstract

Introduction: It is largely accepted that migraine with aura (MA) is caused by cortical spreading depression (CSD) and that migraine without aura (MO) is not. This is mostly based on old studies of regional cerebral blood flow (rCBF) and studies of vascular responses. These studies are partly forgotten today and may, therefore, be worthwhile reviewing.

Methods: The review is based on the authors life-long involvement in these issues and his knowledge of the relevant literature plus scrutiny of reference lists of these papers.

Results: The strongest evidence for CSD in MA came from studies using intraarterial injection of 133-Xenon and recording from 254 areas of the relevant hemisphere. Measurements could be taken before and during development of an attack because the procedure triggered MA. The findings were identical to many features of CSD. They were confirmed using 133-Xenon Single Photon Emission Computerized Tomography (SPECT).It was shown that the generally accepted vasospastic theory of migraine was incorrect. Headache started while rCBF was decreased and did not change during later hyperperfusion. rCBF remained normal in MO but later studies have shown increase in areas also activated by other pain. Flow Was focally increased in the brain stem also after treatment of the pain. Dilatation of large cerebral arteries during MO attack was first shown with ultrasound and later confirmed by MR angiography which also showed a lack of dilatation of extracerebral arteries.

Discussion: Much has in later years been done using modern PET and MR techniques. These studies have confirmed the old studies and have added many new aspects which are not reviewed here. The final proof of CSD during MA and its absence during MO still awaits the definitive study.

Conclusion: Studies from the 1980ies and 1990ies caused a fundamental shift in our understanding of the vascular and cortical mechanisms of migraine. They remain a solid base for our current understanding and inspire further study.

Fig. 1

rCBF measured repeatedly during development of an attack of migraine aura. Top left shows a normal flow distribution in the hemisphere but during successive measurements numbered in the figure a blue area at the posterior pole of the hemisphere appears and it expands gradually forward. These changes are very similar to changes during CSD shown schematically on the right side of the figure. Adapted from Lauritzen et al. [15]

Fig. 2

SPECT study of spontaneous attack of migraine with aura. The top picture shows the initial low flow (blue colour) in the right occipital-parietal area. Below to the left the rCBF has changed into hyperperfusion (red and yellow colour). Finally rCBF is normal and symmetrical in the right sided picture. Modified from [21]

Fig. 3

Schematic drawing of events during and attack of MA. Initially rCBF decreases as the aura develops or even slightly before. After the aura has ended low flow continues into the headache phase. During that phase flow changes from low via normal to increased and it remains increased after the headache has disappeared. These changes and several other features ere totally incompatible with the vasospastic theory of migraine but in agreement with CSD as the underlying cause of the attack. Modified from [4]

Fig. 4

SPECT study of rCBF during an attack of MO. In all such cases rCBF remained normal and symmetrical with the resolution of the technique available that had been able to show focal changes in MA in every case. Subsequent studies with the higher resolution of PET has shown activation in the pain matrix secondary to the pain but nothing that resembles CSD. Modified from [5]