Migraine / PET Study

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Identifier 041-1
Title Migraine / PET Study
Creator Shirley H. Wray, M.D., Ph.D., FRCP, Professor of Neurology Harvard Medical School, Director, Unit for Neurovisual Disorders, Massachusetts General Hospital
Contributor Primary John C. Mazziotta, M.D., Ph.D, UCLA Brain Mapping Center, UCLA School of Medicine
Subject Migraine Headache; Regional Cerebral Blood Flow; Migraine Visual Aura
History In December 1994 the New England Journal of Medicine published a remarkable paper Bilateral Spreading Cerebral Hypoperfusion during Spontaneous Migraine Headache. Roger P. Woods, Marco Iacoboni and John C. Mazziotta. which is reproduced in part, and accompanied by a video illustration. Courtesy of John C. Mazziotta, M.D., Ph.D, UCLA Brain Mapping Center, UCLA School of Medicine. The subject was a 21 year old right handed woman who was recruited as a normal volunteer for the PET study of cerebral blood flow. As an adult, she had had headaches every one to two weeks, some of which were unilateral and associated with nausea, vomiting, or photophobia. Motion or glare from a computer terminal could cause or aggravate her headaches. She had never had migraine with aura or neurologic deficits, and she had no neurologic deficits before, during or after the PET study. The only other family member with headache was a cousin who had migraines. Twelve serial measurements of blood flow were made at 15-minute intervals with the subject in a darkened room, fixating her vision on a computer screen that presented a series of line drawings at a rate of 2/sec. A few minutes after the sixth measurement, she noted the gradual onset of a throbbing headache that she described as a sharp pain in the center of the back of her head, "as if someone had hit me there". The headache worsened with no change in location, during the six subsequent measurements. She also had nausea and photophobia. Interviewed after the study about any symptoms that might be interpreted as those of a migraine with aura, she indicated that during one measurement (the ninth-she thought) she had been unable to focus her vision clearly on the drawings on the screen, although she tried very hard to concentrate on doing so. She indicated otherwise she had looked fixedly at the screen with her eyes open throughout all the measurements. The subject continued to have headache, nausea, mild vertigo, and anorexia after returning home from the study and had headache and nausea for the entire next day, before her condition gradually returned to baseline. For each measurement of blood flow, the subject received an intravenous injection of 10 mCi (370 MBq) of water labeled with oxygen-15. Data were acquired for two minutes after the injection. As compared with shorter imaging times, this approach improves the signal-to-noise ratio but results in a nonlinear relation between blood flow and counts. Three different sets of visual stimuli - A, B, and C - were presented in the order ABCCBAABCCBA during the study. The subject was instructed to view these stimuli passively, maintaining visual fixation on a cross in the center of the screen. Visual fixation was verified immediately before and after each measurement. The PET images were registered to T1-weighted magnetic resonance imaging (MRI) scans as described by Woods RP, Mazziotta JC, Cherry SR. (MRI-PET registration with automated algorithm. J Comput Assist Tomogr 1993;17:536-546). The subdivisions of the images (voxels) that were of potential interest were those in which the blood flow was lowest and decreased the most (to a level at least 20 percent below the base-line value) in studies 7 through 12. Bilateral decreases in blood flow were evident in the subject's occipital regions in the first measurement after the onset of the headache (ie., the seventh measurement), and the decreases progressed anteriorly with time. The authors believe that the most plausible explanation for the blood-flow changes in their subject is that they were the result of spreading depression. Spreading depression, first described by Leao is a transient marked reduction in electrical activity in gray matter in animals that advances contiguously across the cortical surface; the rate of advance is consistent with the spread of symptoms during migraine with aura. It is associated with decreases in blood flow similar in magnitude and duration to those measured in the PET study. Spreading depression can move transcallosally to homologous regions of the opposite hemisphere in animals, and the authors postulate that transcallosal spread accounts for the bilaterality of the findings in their subject. The regions involved earliest were the visual areas known as Brodmann's areas 18 and 19, which are known to have interhemispheric connections through the corpus callosum. Although unilaterality of headache is one of the criteria used in diagnosing migraine, bilateral migraines with aura are well documented. A better understanding of the pathophysiologic features of spreading hypoperfusion would be of obvious clinical importance, since migraine can sometimes lead to ischemic stroke and since stroke can sometimes be aggravated by or associated with the development of migraine.
References 1. Afridi SK, Giffin NJ, Kaube H, Friston KJ, Ward NS, Frackowiak RSJ, Goadsby PJ. A Positron Emission Tomographic Study in Spontaneous Migraine. Arch Neurol 2005;62:1270-1275. http://www.ncbi.nlm.nih.gov/pubmed/16087768 2. Afridi SK, Matharu MS, Lee L, Kaube H, Friston KJ, Frackowiak RSJ, Goadsby PJ. A PET study exploring the laterality of brainstem activation in migraine using glyceryl trinitrate. Brain 2005;128:932-939. http://www.ncbi.nlm.nih.gov/pubmed/15705611 3. Bahra A, Matharu MS, Buchel C, Frackowiak RSJ, Goadsby PJ. Brainstem activation specific to migraine headache. Lancet 2001;357:1016-1017. http://www.ncbi.nlm.nih.gov/pubmed/11293599 4. Goadsby PJ, Lipton RB, Ferrari MD. Migraine - Current Understanding and Treatment. New Engl J Med 2002;346:257-270. http://www.ncbi.nlm.nih.gov/pubmed/11807151 5. Hadjikhani N, Sanchez del Rio M, Wu O, Schwartz D, Bakker D, Fischl B, Kwong KK, Cutrer FM, Rosen BR, Tootell RBH, Sorensen AG, Moskowitz MA. Mechanisms of migraine aura revealed by functional MRI in human visual cortex. Proc Natl Acad Sci USA 2001;98:4687-4692. http://www.ncbi.nlm.nih.gov/pubmed/11287655 6. Lauritzen M. Pathophysiology of the migraine aura: the spreading depression theory. Brain 1994;117:199-210. http://www.ncbi.nlm.nih.gov/pubmed/7908596 7. Leao AAP. Spreading depression of activity in the cerebral cortex. J Neurophysiol 1944;7:359-390. 8. Olesen J, Larsen B, Lauritzen M. Focal hyperemia followed by spreading oligemia and impaired activation of rCBF in classic migraine. Ann Neurol 1981;9:344-352. http://www.ncbi.nlm.nih.gov/pubmed/6784664 9. Storer RJ, Akerman S Goadsby PJ. Calcitonin gene-related peptide (CGRP) modulates nociceptive trigeminovascular transmission in the cat. Brit J Pharm 2004;142:1171-1181. http://www.ncbi.nlm.nih.gov/pubmed/15237097 10. Vijayan N, O'Brien MD, Blau JN, Rastegar D, Woods RP, Iacoboni M, Mazziotta JC, Olesen J. Spreading Cerebral Hypoperfusion during Migraine Headache. N Engl J Med 1995;332:1515-1518. http://www.ncbi.nlm.nih.gov/pubmed/7739695 http://www.ncbi.nlm.nih.gov/pubmed/7739696 http://www.ncbi.nlm.nih.gov/pubmed/7739697 http://www.ncbi.nlm.nih.gov/pubmed/7739698
Contributor Secondary Shirley H. Wray, MD, PhD, FRCP, Professor of Neurology, Harvard Medical School; Director, Unit for Neurovisual Disorders, Massachusetts General Hospital
Publisher Spencer S. Eccles Health Sciences Library, University of Utah
Type Image/MovingImage
Format video/mp4
Rights Management Copyright 2002. For further information regarding the rights to this collection, please visit: https://NOVEL.utah.edu/about/copyright
Holding Institution Spencer S. Eccles Health Sciences Library, University of Utah, 10 N 1900 E, SLC, UT 84112-5890
Collection Neuro-ophthalmology Virtual Education Library: NOVEL http://NOVEL.utah.edu
Language eng
ARK ark:/87278/s6613ww8
Setname ehsl_novel_shw
Date Created 2007-08-09
Date Modified 2017-11-22
ID 188606
Reference URL https://collections.lib.utah.edu/ark:/87278/s6613ww8
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