In Context
Focal point Migraine and headache Harold George Wolff (1898–1962) is considered as a pioneer of modern headache and migraine research, but his career in medicine almost didn’t happen; before taking up a place at Harvard University, he worked in a government fishery, and even contemplated taking holy orders.1 From early in his career, Wolff’s research focused on the neurogenic control of vasoconstriction and vasodilation in migraine and other headache, and he was one of the first neurologists to support the vascular hypothesis, postulating that preheadache phenomena were produced by cerebral vasoconstriction, whereas the headache itself was due to vasodilation of the external carotid arteries and enhanced by subsequent secretion of vasoactive polypeptides in the tissues surrounding the vessels.2 Although vasoactive peptides, such as calcitoningene related peptide, still are implicated in the pathophysiology of migraine (possiblly as a response to the activation of the trigeminovascular system that leads to headache), the aura is now thought to be most likely caused by cortical spreading depression.3 Spreading depression of activity in the cortex was first characterised in 1944 by Aristides Leão4 during experiments to investigate the cortical electrogram readings seen in experimental epilepsy. In these, Leão noted that a marked and prolonged reduction in the spontaneous distinct electrical activity in regions of the cerebral cortex was elicited in response to a brief period of repetitive electrical stimulation. However, the conceptual link between Leão’s spreading depression and migraine was made only some 40 years later, when John Pearce5 cautiously commented on the similarity between the rate of spreading depression and the observed spread of the aura of classic migraine, raising the possibilities that spreading depression was the initiating event in migraine and that migraine was a cerebral disorder.
Steven Goodrick 1 2 3
4 5
Blau JN. H G Wolff: the man and his migraine. Cephalalgia 2004; 24: 215–22. Wolff HG. Headache and other head pain. New York: Oxford University Press, 1963. Ferrari MD, Klever RR, Terwindt GM, Ayata C, van den Maagdenberg AMJM. Migraine pathophysiology: lessons from mouse models and human genetics. Lancet Neurol 2015; 14: 65–80. Leão AAP. Spreading depression of activity in the cerebral cortex. J Neurophysiol 1944; 7: 359–90. Pearce JMS. Is migraine explained by Leão’s spreading depression? Lancet 1985; 326: 763–66.
www.thelancet.com/neurology Vol 14 January 2015
Lifeline Victor Villemagne is an associate professor at the Department of Medicine at the University of Melbourne, Australia. After a post-doctorate in nuclear medicine at the Johns Hopkins School of Medicine (Baltimore, MD, USA), he continued his research at the National Institute on Drug Abuse, National Institutes of Health, and University of Pittsburgh (PA, USA). His main research interest is the in-vivo imaging of brain pathology in ageing and neurodegenerative disorders. What would be your advice to a newly qualified doctor? Follow the Hippocratic injunction: primun non nocere.
See Review page 114
Who was your most influential teacher, and why? There were two: Angel Faretta and Henry N Wagner Jr. They both opened my eyes, one by teaching me how to progress from æsthetics to metaphysics in a Kierkegaardian way; the other by teaching me a wise and discerning approach to interpreting PET scans. How do you relax? Reading G K Chesterton, listening to Richard Wagner, and watching John Ford movies. What is your favourite film, and why? The Searchers by John Ford. Ford always reminds us of what the world should have been. His art, like all high art, ennobles the soul. What are you currently reading? Starting The Temple of the Golden Pavillion by Yukio Mishima, half-way through The Emperor’s Tomb by Joseph Roth, and finishing The Confederacy of Dunces by John Kennedy Toole. In which other place would you like to live and why? San Gimignano, Italy. It is a town that conveys the liberating feeling that the world can’t reach you up there… while enjoying a great wine and a fantastic meal. Do you believe there are other life forms in the Universe? Certainly. The taxonomy is already available in the Cælestis hierarchia by Dionysius the Areopagite. What was the most memorable comment you ever received from a referee? That my writing was “slightly melodramatic”. I almost took offense to it because it was not true…I am always overly melodramatic. You can have dinner tonight with a famous person of your choice (dead or alive), who would it be? Oscar Wilde. What is the naughtiest thing you have ever done? If you were caught what, if anything, did you learn? When I was about 10, I forged my father’s signature on a school report. Of course, I was caught. I learned I needed more practice. 35
Focal point Migraine and headache Harold George Wolff (1898–1962) is considered as a pioneer of modern headache and migraine research, but his career in medicine almost didn’t happen; before taking up a place at Harvard University, he worked in a government fishery, and even contemplated taking holy orders.1 From early in his career, Wolff’s research focused on the neurogenic control of vasoconstriction and vasodilation in migraine and other headache, and he was one of the first neurologists to support the vascular hypothesis, postulating that preheadache phenomena were produced by cerebral vasoconstriction, whereas the headache itself was due to vasodilation of the external carotid arteries and enhanced by subsequent secretion of vasoactive polypeptides in the tissues surrounding the vessels.2 Although vasoactive peptides, such as calcitoningene related peptide, still are implicated in the pathophysiology of migraine (possiblly as a response to the activation of the trigeminovascular system that leads to headache), the aura is now thought to be most likely caused by cortical spreading depression.3 Spreading depression of activity in the cortex was first characterised in 1944 by Aristides Leão4 during experiments to investigate the cortical electrogram readings seen in experimental epilepsy. In these, Leão noted that a marked and prolonged reduction in the spontaneous distinct electrical activity in regions of the cerebral cortex was elicited in response to a brief period of repetitive electrical stimulation. However, the conceptual link between Leão’s spreading depression and migraine was made only some 40 years later, when John Pearce5 cautiously commented on the similarity between the rate of spreading depression and the observed spread of the aura of classic migraine, raising the possibilities that spreading depression was the initiating event in migraine and that migraine was a cerebral disorder.
Steven Goodrick 1 2 3
4 5
Blau JN. H G Wolff: the man and his migraine. Cephalalgia 2004; 24: 215–22. Wolff HG. Headache and other head pain. New York: Oxford University Press, 1963. Ferrari MD, Klever RR, Terwindt GM, Ayata C, van den Maagdenberg AMJM. Migraine pathophysiology: lessons from mouse models and human genetics. Lancet Neurol 2015; 14: 65–80. Leão AAP. Spreading depression of activity in the cerebral cortex. J Neurophysiol 1944; 7: 359–90. Pearce JMS. Is migraine explained by Leão’s spreading depression? Lancet 1985; 326: 763–66.
www.thelancet.com/neurology Vol 14 January 2015
Lifeline Victor Villemagne is an associate professor at the Department of Medicine at the University of Melbourne, Australia. After a post-doctorate in nuclear medicine at the Johns Hopkins School of Medicine (Baltimore, MD, USA), he continued his research at the National Institute on Drug Abuse, National Institutes of Health, and University of Pittsburgh (PA, USA). His main research interest is the in-vivo imaging of brain pathology in ageing and neurodegenerative disorders. What would be your advice to a newly qualified doctor? Follow the Hippocratic injunction: primun non nocere.
See Review page 114
Who was your most influential teacher, and why? There were two: Angel Faretta and Henry N Wagner Jr. They both opened my eyes, one by teaching me how to progress from æsthetics to metaphysics in a Kierkegaardian way; the other by teaching me a wise and discerning approach to interpreting PET scans. How do you relax? Reading G K Chesterton, listening to Richard Wagner, and watching John Ford movies. What is your favourite film, and why? The Searchers by John Ford. Ford always reminds us of what the world should have been. His art, like all high art, ennobles the soul. What are you currently reading? Starting The Temple of the Golden Pavillion by Yukio Mishima, half-way through The Emperor’s Tomb by Joseph Roth, and finishing The Confederacy of Dunces by John Kennedy Toole. In which other place would you like to live and why? San Gimignano, Italy. It is a town that conveys the liberating feeling that the world can’t reach you up there… while enjoying a great wine and a fantastic meal. Do you believe there are other life forms in the Universe? Certainly. The taxonomy is already available in the Cælestis hierarchia by Dionysius the Areopagite. What was the most memorable comment you ever received from a referee? That my writing was “slightly melodramatic”. I almost took offense to it because it was not true…I am always overly melodramatic. You can have dinner tonight with a famous person of your choice (dead or alive), who would it be? Oscar Wilde. What is the naughtiest thing you have ever done? If you were caught what, if anything, did you learn? When I was about 10, I forged my father’s signature on a school report. Of course, I was caught. I learned I needed more practice. 35
