migraine-resuscitation of the vascular theory

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Editorial Migraine-Resuscitation of the Vascular Theory John Edmeads, M.D. When physicians seeking to explain migraine began to look past the Galenical miasma of humours and spirits, they came upon the circulatory system, newly illuminated for them by William Harvey (1628). Thomas Willis (1621-1675) hypothesized that "megri m" was due to dilatation of cephalic blood vessels. The migraine aura waited two centuries for its explanation, till 1870 when Airy, analyzing his own symptoms, suggested "a temporary suspension of function...among the nerve cells of the visual senso rium...due to vascular congestion." P.W. Latham in 1872 believed "a contraction of the vessels of the head and anemia of the parts they supply" to be "the immediate occasion of the paroxysm, and the cause of the earlier symptoms and particularly of t he disorder of sight; while the headache"... is due... "to a secondary hyperemia. "1 Latham's friend and colleague, Edward Liveing, disagreed, and argued that migraine was caused by "nerve storms" which were the result of "a discharging lesions of con volutions evolved out of the optic thalamus." He regarded migraine as "primarily nervous" and held that any disturbance of the circulation which attended it was an effect of the nervous disorder. 2 Thus, a century ago, the lines were drawn between the supporters of the vascular theory and those of the neurogenic theory, and the controversy was brisk. This was a battle of hypotheses and authorities. There was no experimental evidence, for there had been no experiments. The observations of Maier and of Tzank in the 1920's that migraine could be aborted by ergotamine were as close to experiment as anyone had gone, and were enormously influential. Ergotamine was then regarded as having primari ly vascular effects, and its efficacy in dispelling migraine seemed strong evidence that migraine had to be a vascular disorder. The subsequent body of laboratory investigation by Harold Wolff and his colleagues proceeded from this assumption, and am assed much evidence which established the supremacy of the vascular theory. Ironically, it was a study of cerebral blood flow that rescued the neurogenic theory from oblivion and put the vascular theory into the discard. In 1981, using an advanced technology which permitted simultaneous and rapidly repeatable sampling of reg ional cerebral blood flow (rCBF) in 254 areas of cerebral hemisphere, Jes Olesen and his colleagues in Copenhagen described "spreading oligemia" during attacks of classic migraine. 3 Brief hyperemia was followed by a longer lasting tide of decreased r CBF which spread forwards from the occipital region, traversing the cortex at a velocity of 2-3 millimeters per minute and, importantly, trespassing the boundaries of distribution of the larger blood vessels, making it unlikely that the oligemia was related to spasm. Though Olesen et al were cautious in interpreting this finding, commentators seized upon it eagerly, pointing to the similarity to the cortical spreading depression of Leao and to the calculations of Lash-Icy 4 that his visual auras seemed to reflect a spreading neurophysiologic process traversing his occipital cortex at 2-3 millimeters per minute; and stating that migraine had to be a neurogenic phenomenon. Reinforcing the renaissance of the neurogenic theory was the work of La nce and his colleagues 5 which demonstrated that in the animal stimulation of the locus caeruleus could produce changes in cerebral blood flow similar to those recorded in man in migraine. For the past seven years the neurogenic theory has ruled supreme. Clinical observations have been explained in neurophysiologic terms, and the efficacy of anti-migraine drugs has been attributed to their effect on the brain rather than on the vascula r system. It is doubly ironic, therefore, that it is another paper on rCBF from Copenhagen that may have torn the foundations away from the current upsurge of the neurogenic theory. Tom Skyhoj Olsen and Niels Lassen, report in this issue of HEADACHE their anal ysis of the effects of Compton scatter on the interpretation of rCBF studies in migraine. They point out that "the recording of a low flow area which spreads to involve larger and larger areas of the brain does not mean that such a spreading process actually exists. As a matter of fact this phenomenon may reflect the presence of a territory with a fixed size in which CBF gradually decreases with time. Spreading may, thus, be an artefact caused by the effect of Compton scatter in a period when CB F decreases in a territory of constant size." "Having been interpreted as favouring a neurogenic origin of classic migraine, the data are also, with the Compton effect in mind, compatible with a vascular genesis.'' 6 This paper is published as the first in HEADACHE for 1989 because we feel that this position reflects its potential significance. This editorial is cast in historical terms because we feel that only a long view will put the paper of Skyhoj Olsen and Lassen into perspective. Theories and interpretations come and go. The observed phenomena of migraine remain. As the poet Robert Frost said, "Most of the change we think we see in life is due to truths being in and out of favour." If we swing between vascular and neurogenic views of migraine, it is probably because

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Editorial

Migraine-Resuscitation of the Vascular Theory

John Edmeads, M.D.

When physicians seeking to explain migraine began to look past the Galenical miasma of humours andspirits, they came upon the circulatory system, newly illuminated for them by William Harvey (1628). ThomasWillis (1621-1675) hypothesized that "megrim" was due to dilatation of cephalic blood vessels. The migraineaura waited two centuries for its explanation, till 1870 when Airy, analyzing his own symptoms, suggested "atemporary suspension of function...among the nerve cells of the visual sensorium...due to vascularcongestion." P.W. Latham in 1872 believed "a contraction of the vessels of the head and anemia of the partsthey supply" to be "the immediate occasion of the paroxysm, and the cause of the earlier symptoms andparticularly of the disorder of sight; while the headache"... is due... "to a secondary hyperemia."1 Latham'sfriend and colleague, Edward Liveing, disagreed, and argued that migraine was caused by "nerve storms"which were the result of "a discharging lesions of convolutions evolved out of the optic thalamus." Heregarded migraine as "primarily nervous" and held that any disturbance of the circulation which attended itwas an effect of the nervous disorder.2

Thus, a century ago, the lines were drawn between the supporters of the vascular theory and those of theneurogenic theory, and the controversy was brisk. This was a battle of hypotheses and authorities. There wasno experimental evidence, for there had been no experiments. The observations of Maier and of Tzank in the1920's that migraine could be aborted by ergotamine were as close to experiment as anyone had gone, andwere enormously influential. Ergotamine was then regarded as having primarily vascular effects, and itsefficacy in dispelling migraine seemed strong evidence that migraine had to be a vascular disorder. Thesubsequent body of laboratory investigation by Harold Wolff and his colleagues proceeded from thisassumption, and amassed much evidence which established the supremacy of the vascular theory.

Ironically, it was a study of cerebral blood flow that rescued the neurogenic theory from oblivion and putthe vascular theory into the discard. In 1981, using an advanced technology which permitted simultaneousand rapidly repeatable sampling of regional cerebral blood flow (rCBF) in 254 areas of cerebral hemisphere,Jes Olesen and his colleagues in Copenhagen described "spreading oligemia" during attacks of classicmigraine.3 Brief hyperemia was followed by a longer lasting tide of decreased rCBF which spread forwardsfrom the occipital region, traversing the cortex at a velocity of 2-3 millimeters per minute and, importantly,trespassing the boundaries of distribution of the larger blood vessels, making it unlikely that the oligemia wasrelated to spasm. Though Olesen et al were cautious in interpreting this finding, commentators seized upon iteagerly, pointing to the similarity to the cortical spreading depression of Leao and to the calculations ofLash-Icy4 that his visual auras seemed to reflect a spreading neurophysiologic process traversing his occipitalcortex at 2-3 millimeters per minute; and stating that migraine had to be a neurogenic phenomenon.Reinforcing the renaissance of the neurogenic theory was the work of Lance and his colleagues5 whichdemonstrated that in the animal stimulation of the locus caeruleus could produce changes in cerebral bloodflow similar to those recorded in man in migraine.

For the past seven years the neurogenic theory has ruled supreme. Clinical observations have beenexplained in neurophysiologic terms, and the efficacy of anti-migraine drugs has been attributed to their effecton the brain rather than on the vascular system.

It is doubly ironic, therefore, that it is another paper on rCBF from Copenhagen that may have torn thefoundations away from the current upsurge of the neurogenic theory. Tom Skyhoj Olsen and Niels Lassen,report in this issue of HEADACHE their analysis of the effects of Compton scatter on the interpretation ofrCBF studies in migraine. They point out that "the recording of a low flow area which spreads to involve largerand larger areas of the brain does not mean that such a spreading process actually exists. As a matter of factthis phenomenon may reflect the presence of a territory with a fixed size in which CBF gradually decreaseswith time. Spreading may, thus, be an artefact caused by the effect of Compton scatter in a period when CBFdecreases in a territory of constant size." "Having been interpreted as favouring a neurogenic origin of classicmigraine, the data are also, with the Compton effect in mind, compatible with a vascular genesis.''6

This paper is published as the first in HEADACHE for 1989 because we feel that this position reflects itspotential significance. This editorial is cast in historical terms because we feel that only a long view will put thepaper of Skyhoj Olsen and Lassen into perspective. Theories and interpretations come and go. The observedphenomena of migraine remain. As the poet Robert Frost said, "Most of the change we think we see in life isdue to truths being in and out of favour." If we swing between vascular and neurogenic views of migraine, it isprobably because

both vascular and neurogenic mechanisms for migraine exist and are important.

REFERENCES

1. Liveing E: On Megrim Sick-Headache and Some Allied Disorders: A Contribution to the Pathology ofNerve-Storms. London. J & A Churchill. 1873. p 319.

2. Op Cit. p 391.

3. Olesen J, Larsen B, Lauritzen M: Focal hyperemia followed by spreading oligemia and impairedactivation of rCBF in classic migraine. Ann Neurol 9:344-352, 1981.

4. Lashley KS: Patterns of cerebral integration indicated by syndromes of migraine. Arch Neurol Psychiat46:331-339, 1941.

5. Lance JW, Lambert GA, Goadsby PJ, Duckworth JW: Brainstem influences on the cephaliccirculation: experimental data from cat and monkey of relevance to the mechanisms of migraine.Headache 23:258-265, 1985.

6. Skyhoj Olsen T, Lassen NA: Blood flow and vascular reactivity during attacks of classicmigraine-limitations of the Xe-133 intraarterial technique. Headache 29: 15-20, 1989.