s39 Clinical Neurology and Neuromrgety, 94 (Suppl.) (1992) S39 -S40 (B 1992 Elsevier Science Publishers B.V. All rights resewed 0303~8467/92/$05.00 CNN 00102
Migraine: questions and thoughts J.N. Blau National Hospital for Neurology and Neurosurgery, Queen Square, London WCIN 3 BG (UX)
Key words: Migraine Dear George “Question everything at least once, including that 2 + 2 = 4” - an invaluable aphorism from Georg Lichtenberg with whom you have a number of things in common: your first name, you are both thoroughly grounded in your own fields, philosophy, i.e. deep thinking, a great sense of humor, and full of penetrating witticisms. The right question being the essence of advancing a subject and seeing how we, and others, can go wrong, let me pose and explore a few questions, on which I would like to hear your views. 1. How did Harold Wolff convince himselj and the whole medical profession, of the incorrect notion that migraine headaches were due to extracranial vasodilatation? Hughlings Jackson said that it took 50 years to get a bad idea out of medicine and a 100 years to get a good idea into medicine (Critchley, personal communication). I have no doubt that Wolff’s postulated mechanism for migraine plus the hedging phrase “a vascular headache of the migraine type” (which I suspect was his) certainly hindered progress for at least 40 years. Talking to doctors who worked for Harold Wolff I have learnt that he had migraine himself, that he sat in his office during attacks with a finger pressing on his superficial temporal artery to lessen (not abolish) his headache, and that he did not allow, let alone invite, criticism of himself. Reading his original paper with Tunis [l], he presented “selected tracings” to illustrate his hypothesis. However, even on his own illustrations it is evident that 36 to 48 hours before the onset of headache, the amplitude of the tracings of the superficial temporal artery were the same as at the height of an attack - graded 7+ out of 10. Hence the temporal artery pulsations are, as you put it, a Correspondence to: J.N. Blau, MD, FRCP, FRCPath, National Hospital for Neurology and Neurosurgery, Queen Square, London WClN BG, U.K.
line example of “mental torsion-dystonia”. We know that the majority of patients lie still during a migraine because head movement increases the headache, indeed any practicing neurologist knows that headache, vomiting and photophobia, as well as the jolt manoeuvre are characteristic of meningeal irritation. Of course many doctors interested in migraine have that condition themselves. Is that good or bad? Good because it makes them more human; bad because often it is the only type that they are prepared to accept. 2. What gave you the idea that neuroglia may be involved in the migraine process [2]? I believe this is a brilliant idea and, as most original thoughts, totally neglected. I say brilliant because neuroglia constitute a vast cellular system in the brain, and as Einstein said “God does not play with dice” - which means that neuroglia must have some function in relation to neurones. Your idea was that glia mop up potassium ions released from overstimulated neurones, and that the released potassium spreads from the excited focus, let us say in the occipital cortex, and then permeates adjacent areas, producing the migrating teichopsia or enlarging scotoma. Next you propose astrocytic swelling accounting for “my brain feels swollen” or “my skull feels as if it is bursting open” which patients so often describe, Here, perhaps, we can modify the truism “listen to the patient he is telling you the diagnosis” to “listen to the patient she is telling you the mechanism”. Unfortunately our recent studies on four patients examined with MRI during and between migraine attacks failed to demonstrate any oedema [3]. I need hardly add that the hardened research worker is never put off by failure but strives on: the method is probably inadequate to show microscopic changes. Nevertheless, why do we not take the next step - to the heart of the matter?
3. Can neurones themselves of migraine?
be over-stimulated
as the cause
I am sure you will say immediately that is where Gowers put the trouble 141. So he did but “if I have seen further it is by standing on the shoulders of giants” Newton’s remark to Robert Hook in 1675 -- and WCcannot do much better than that, can we? I would like to hear your thoughts on how we calculate that 2 i- 2 = 4. My own view is that this computation is carried out by neurones themselves which need neurotransmitters to act in unison; but it is not the ncurotransmitters or the synapses that are responsible for mental or, for that matter, physical activities. I cannot understand the current emphasis of neurotransmitters as the mechanism of all brain activity. Perhaps because they are measurable, or, more likely fashionable, neurotransmitters are the current bandwagon to which depression, anorexia nervosa, obsessive compulsive behavior, hunger, sleep and migraine are attributed - a panacea for the intellectually destitute. Even if these conditions were curable by 5-HT antagonists (which they are not) it does not follow that neurotransmitters are the active agents. (Pharmacologists on this basis would argue that the effective treatment of pneumonia with penicillin means that the patient was penicillin deficient!) To me neurotransmitters are like hospital administrators, busily sending memoranda to various departments but someone else has to do the work. People also forget that “science is built up of facts, as a house, but an ac&umulation of facts is no more science that a heap of stones is a house”, as stated by Poincare
many years ago [5]. Of course, there arc plenty of pebble gatherers around. Returning to migraine and patients’ expcricnces, the stimuli for attacks include stress, hunger, alcohol, too much or too little sleep, heat, light, noise, travel and shopping. All these stimuli go straight to the neurones, not to platelets and not to blood vessels. Yes, vessels are involved in the process but secondary - remember Gowers analogy with blushing? Of course, neurones are hard to investigate, and it is easy to get a paper, or get rich quickly, or a grant out of neurotransmitters, but good research is difficult and good ideas are hard to come by. So George I hope you will keep actively thinking and writing in your retirement when I suspect you will have a little more time and feel freer not having to run your department. Perhaps you will let me have a reply to some of the notions I have put to you here. My best wishes for your continuing neuronal activity. As ever, Nat
References Tunis MM, Wolff IIG. Am J Med Sci 1952; 224: 56.5~5%. Bruyn GW. In Amery WK, Van Neuten JM, Wauquier A (eds.), The Pharmacological Basis of Migraine Therapy. London: Pitman, 1984; 267-278. Barnes D, Blau JN, Kingsley DPE, Kendall BE. Lancet 1991; 337: 135940. Gowers WR. A Manual of Diseases of the Nervous System, vat II. London: Churchill, 1888; 774-795. Poincarg II. Science and Hypothesis. New York: Dover, 1952; 141.
Migraine: questions and thoughts J.N. Blau National Hospital for Neurology and Neurosurgery, Queen Square, London WCIN 3 BG (UX)
Key words: Migraine Dear George “Question everything at least once, including that 2 + 2 = 4” - an invaluable aphorism from Georg Lichtenberg with whom you have a number of things in common: your first name, you are both thoroughly grounded in your own fields, philosophy, i.e. deep thinking, a great sense of humor, and full of penetrating witticisms. The right question being the essence of advancing a subject and seeing how we, and others, can go wrong, let me pose and explore a few questions, on which I would like to hear your views. 1. How did Harold Wolff convince himselj and the whole medical profession, of the incorrect notion that migraine headaches were due to extracranial vasodilatation? Hughlings Jackson said that it took 50 years to get a bad idea out of medicine and a 100 years to get a good idea into medicine (Critchley, personal communication). I have no doubt that Wolff’s postulated mechanism for migraine plus the hedging phrase “a vascular headache of the migraine type” (which I suspect was his) certainly hindered progress for at least 40 years. Talking to doctors who worked for Harold Wolff I have learnt that he had migraine himself, that he sat in his office during attacks with a finger pressing on his superficial temporal artery to lessen (not abolish) his headache, and that he did not allow, let alone invite, criticism of himself. Reading his original paper with Tunis [l], he presented “selected tracings” to illustrate his hypothesis. However, even on his own illustrations it is evident that 36 to 48 hours before the onset of headache, the amplitude of the tracings of the superficial temporal artery were the same as at the height of an attack - graded 7+ out of 10. Hence the temporal artery pulsations are, as you put it, a Correspondence to: J.N. Blau, MD, FRCP, FRCPath, National Hospital for Neurology and Neurosurgery, Queen Square, London WClN BG, U.K.
line example of “mental torsion-dystonia”. We know that the majority of patients lie still during a migraine because head movement increases the headache, indeed any practicing neurologist knows that headache, vomiting and photophobia, as well as the jolt manoeuvre are characteristic of meningeal irritation. Of course many doctors interested in migraine have that condition themselves. Is that good or bad? Good because it makes them more human; bad because often it is the only type that they are prepared to accept. 2. What gave you the idea that neuroglia may be involved in the migraine process [2]? I believe this is a brilliant idea and, as most original thoughts, totally neglected. I say brilliant because neuroglia constitute a vast cellular system in the brain, and as Einstein said “God does not play with dice” - which means that neuroglia must have some function in relation to neurones. Your idea was that glia mop up potassium ions released from overstimulated neurones, and that the released potassium spreads from the excited focus, let us say in the occipital cortex, and then permeates adjacent areas, producing the migrating teichopsia or enlarging scotoma. Next you propose astrocytic swelling accounting for “my brain feels swollen” or “my skull feels as if it is bursting open” which patients so often describe, Here, perhaps, we can modify the truism “listen to the patient he is telling you the diagnosis” to “listen to the patient she is telling you the mechanism”. Unfortunately our recent studies on four patients examined with MRI during and between migraine attacks failed to demonstrate any oedema [3]. I need hardly add that the hardened research worker is never put off by failure but strives on: the method is probably inadequate to show microscopic changes. Nevertheless, why do we not take the next step - to the heart of the matter?
3. Can neurones themselves of migraine?
be over-stimulated
as the cause
I am sure you will say immediately that is where Gowers put the trouble 141. So he did but “if I have seen further it is by standing on the shoulders of giants” Newton’s remark to Robert Hook in 1675 -- and WCcannot do much better than that, can we? I would like to hear your thoughts on how we calculate that 2 i- 2 = 4. My own view is that this computation is carried out by neurones themselves which need neurotransmitters to act in unison; but it is not the ncurotransmitters or the synapses that are responsible for mental or, for that matter, physical activities. I cannot understand the current emphasis of neurotransmitters as the mechanism of all brain activity. Perhaps because they are measurable, or, more likely fashionable, neurotransmitters are the current bandwagon to which depression, anorexia nervosa, obsessive compulsive behavior, hunger, sleep and migraine are attributed - a panacea for the intellectually destitute. Even if these conditions were curable by 5-HT antagonists (which they are not) it does not follow that neurotransmitters are the active agents. (Pharmacologists on this basis would argue that the effective treatment of pneumonia with penicillin means that the patient was penicillin deficient!) To me neurotransmitters are like hospital administrators, busily sending memoranda to various departments but someone else has to do the work. People also forget that “science is built up of facts, as a house, but an ac&umulation of facts is no more science that a heap of stones is a house”, as stated by Poincare
many years ago [5]. Of course, there arc plenty of pebble gatherers around. Returning to migraine and patients’ expcricnces, the stimuli for attacks include stress, hunger, alcohol, too much or too little sleep, heat, light, noise, travel and shopping. All these stimuli go straight to the neurones, not to platelets and not to blood vessels. Yes, vessels are involved in the process but secondary - remember Gowers analogy with blushing? Of course, neurones are hard to investigate, and it is easy to get a paper, or get rich quickly, or a grant out of neurotransmitters, but good research is difficult and good ideas are hard to come by. So George I hope you will keep actively thinking and writing in your retirement when I suspect you will have a little more time and feel freer not having to run your department. Perhaps you will let me have a reply to some of the notions I have put to you here. My best wishes for your continuing neuronal activity. As ever, Nat
References Tunis MM, Wolff IIG. Am J Med Sci 1952; 224: 56.5~5%. Bruyn GW. In Amery WK, Van Neuten JM, Wauquier A (eds.), The Pharmacological Basis of Migraine Therapy. London: Pitman, 1984; 267-278. Barnes D, Blau JN, Kingsley DPE, Kendall BE. Lancet 1991; 337: 135940. Gowers WR. A Manual of Diseases of the Nervous System, vat II. London: Churchill, 1888; 774-795. Poincarg II. Science and Hypothesis. New York: Dover, 1952; 141.
