As the "Circle Turns Round" Back to Neurovascular Basis in Migraine
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《美国整骨期刊》
We are in the midst of an evolution of thinking about migraine headache as we move through the first decade of the 21st century. This evolution, however, has been in progress for more than 100 years. At the close of the 19th century, Living termed migraine a "neurologic storm."1 For many years thereafter the neurologic basis of migraine held sway until the advent of the work on ergotamine by Harold G. Wolff, MD, among others.
Wolff's pioneering work certainly could hardly be duplicated, from inserting mercury-filled balloons into the nasal sinuses to study the amount of pressure required to cause pain to his having neurosurgeons drill burr holes in the skulls of his patients with migraine during their attacks so that he could study what happens within the skull during a migraine. That was in the days before magnetic resonance imaging (MRI), positive-emission tomography (PET), and single photon emission computer tomography (SPECT). Wolff's studies led him to believe in the vascular theories he suggested in migraine.2
Over time, the pendulum swung again, or rather, the circle more turned round and we ended back at viewing migraine as having a neurologic basis. This time, however, our understanding of biology and biochemistry improved, and we came to recognize the interplay between the neurologic and vascular systems in creating the symptomatology of migraine. As we have moved from the end of the 20th century into the 21st century, our ability to use noninvasive tools such as MRI, PET, and SPECT, and biochemical markers opened our clinical eyes to the subtle interplays in systems and symptoms. Thus, we have gained new understanding of neurovascular mechanisms of migraine, and we are beginning to appreciate the ramifications of these findings for treatment, as well as to examine the implications for the prognosis of migraine's impact on our patients for years to come. And, that is what brings us to this special issue.
The articles in this supplement, written by physicians—DOs as well as MDs—recognized as leaders in headache research and treatment, address four seemingly widely disparate, but truly interlinked, topics.
Andrew D. Hershey, MD, PhD, and Paul K. Winner, DO, the president elect of the American Headache Society, address the issue of pediatric migraine. Next, George R. Nissan, DO, and Merle L. Diamond, MD, two of my colleagues from the Diamond Headache Clinic in Chicago, provide a review of advances in migraine treatment, both conceptually as well as specifically. Next, David M. Biondi, DO, discusses cervicogenic headache. As you will have seen from Drs Nissan and Diamond's review, Dr Biondi's article has great significance in our approach to patients with a challenging headache problem. Last, Stephen D. Silberstein, MD, president of the American Headache Society, discusses the diagnostic and basic treatment considerations in patients with chronic headache.
Migraine may afflict the young and old and has its most devastating effect all too often on those at their peak of productivity in their 30s, 40s, and 50s. Beginning in childhood in a small percentage of the population, the numbers quickly increase as adolescence begins. Epidemiologic studies suggest that many of these children with migraine will continue to have headaches for many years.
The US Food and Drug Administration has encouraged research of new therapeutic agents in the pediatric age group. While the studies in migraine are proving newer agents safe, they have met challenges in proving efficacy because of high placebo response rates. This may be an artifactual issue related to study design and the clinical setting in which many teenagers treat their headaches, that is, at school. Early education of this age group in proper migraine therapy with medication and self-help techniques needs to be encouraged, and long-term studies of these efforts need to be conducted to determine the potential impact on altering the natural history of migraine.
By the time patients in their adult years have had migraine for a number of years, processes such as central sensitization and cutaneous allodynia become more common and the risk factors associated with lifestyle and comorbid medical and psychological illnesses may contribute to the potential for migraine's becoming increasingly refractive to treatment to both medications for acute attacks and to preventive therapy. Just having migraine over the course of years may in itself be a risk factor for this process. Early intervention in the acute attack of migraine may change the outcome if achieved before patients become allodynic. How this impacts the patient over the course of time has yet to be elucidated. Clinically, an attempt to reduce the overall frequency of migraine through preventive techniques appears to improve short-term therapeutic outcomes and may be beneficial for the long-term prognosis.
Although some patients with episodic migraine convert to a chronic stage each year, fewer revert from the chronic stage to episodic migraine. The reasons for these transitions to chronic headache are being understood with increasing clarity, but we can only surmise that improvements in quality of care and resolution of risk factors for chronic headache may play a role in such transitions.
Factors that play a role in the problem in migraine management include misdiagnosis. We need to consider overlap presentations, which may be driven by neuroanatomic issues, in our approach to patients with headache. Although some would tend to put all the patients with daily headaches into a single group, it is important to be able to clinically distinguish between them. We need to identify factors that contribute to the development of the daily headache and treat patients accordingly, as this approach by itself may allow for resolution of the daily headache phase. Additionally, therapeutics that work well for one disorder such as migraine may not work well for another such as tension-type headache including when the disorder becomes chronic, as seen in the work with botulinum toxin type A and other agents, as well.
Improvements in our ability to study migraine's pathophysiology and develop sound therapeutic approaches based on these studies may lead to altering the long-term prognosis for patients with this disorder. Migraine is the leading cause of painful disability in the United States in this age; yet, our appreciation for it often has been clouded by outmoded ideas of disease management and lack of understanding of optimal therapeutic utilization.
It is hoped that the concepts and information presented in this series of articles will enhance your knowledge of migraine and its treatment and improve the well-being of your patients.
Footnotes
Dr Freitag has received grants and/or conducted research for Abbott Laboratories; Allergan; AstraZeneca; Bristol-Myers Squibb; CAPNIA; Elan Pharmaceuticals; Eli Lilly and Company; EpiCept; GlaxoSmithKline; Merck & Co, Inc; Novartis; NPS Pharmaceuticals; and Ortho-McNeil Pharmaceuticals. He has served as a consultant to Abbott Laboratories; Allergan; AstraZeneca; Bristol-Myers Squibb; CAPNIA; Elan Pharmaceuticals, Inc; Eli Lilly and Company; EpiCept; GlaxoSmithKline; Interpharm Pharmaceuticals; Medpointe Pharmaceuticals; Merck & Co, Inc; Novartis; NPS Pharmaceuticals; Ortho-McNeil Pharmaceuticals; Pozen, Inc; Solvay Pharmaceuticals; and Xcel Pharmaceuticals. Dr Freitag has also served on the speakers bureau of Abbott Laboratories; AstraZeneca; Bristol-Myers Squibb; GlaxoSmithKline, Medpointe Pharmaceuticals; Merck & Co,Inc; Ortho-McNeil Pharmaceuticals; Pfizer Inc; and Xcel Pharmaceuticals.
This continuing medical education publication supported by an unrestricted educational grant from Merck & Co, Inc
Dr Freitag is associate director of the Diamond Headache Clinic in Chicago, Ill; an affiliate instructor in the Department of Family Medicine at Midwestern University's Chicago College of Osteopathic Medicine in Downers Grove, Ill; and a clinical associate professor in the Department of Family Medicine at Rosalind Franklin University of Medicine and Science/Chicago Medical School in North Chicago, Ill.
References
1. Living E. On Megrim, Sick Headache, and Some Allied Disorders: A Contribution to the Pathophysiology of Nerve-Storms. London, England: J and A Churchill; 1873:335 -395.
2. Wolff HG. Headache and Other Head Pain. New York, NY: Oxford University Press; 1948:261 -286.(Frederick G. Freitag, DO)
Wolff's pioneering work certainly could hardly be duplicated, from inserting mercury-filled balloons into the nasal sinuses to study the amount of pressure required to cause pain to his having neurosurgeons drill burr holes in the skulls of his patients with migraine during their attacks so that he could study what happens within the skull during a migraine. That was in the days before magnetic resonance imaging (MRI), positive-emission tomography (PET), and single photon emission computer tomography (SPECT). Wolff's studies led him to believe in the vascular theories he suggested in migraine.2
Over time, the pendulum swung again, or rather, the circle more turned round and we ended back at viewing migraine as having a neurologic basis. This time, however, our understanding of biology and biochemistry improved, and we came to recognize the interplay between the neurologic and vascular systems in creating the symptomatology of migraine. As we have moved from the end of the 20th century into the 21st century, our ability to use noninvasive tools such as MRI, PET, and SPECT, and biochemical markers opened our clinical eyes to the subtle interplays in systems and symptoms. Thus, we have gained new understanding of neurovascular mechanisms of migraine, and we are beginning to appreciate the ramifications of these findings for treatment, as well as to examine the implications for the prognosis of migraine's impact on our patients for years to come. And, that is what brings us to this special issue.
The articles in this supplement, written by physicians—DOs as well as MDs—recognized as leaders in headache research and treatment, address four seemingly widely disparate, but truly interlinked, topics.
Andrew D. Hershey, MD, PhD, and Paul K. Winner, DO, the president elect of the American Headache Society, address the issue of pediatric migraine. Next, George R. Nissan, DO, and Merle L. Diamond, MD, two of my colleagues from the Diamond Headache Clinic in Chicago, provide a review of advances in migraine treatment, both conceptually as well as specifically. Next, David M. Biondi, DO, discusses cervicogenic headache. As you will have seen from Drs Nissan and Diamond's review, Dr Biondi's article has great significance in our approach to patients with a challenging headache problem. Last, Stephen D. Silberstein, MD, president of the American Headache Society, discusses the diagnostic and basic treatment considerations in patients with chronic headache.
Migraine may afflict the young and old and has its most devastating effect all too often on those at their peak of productivity in their 30s, 40s, and 50s. Beginning in childhood in a small percentage of the population, the numbers quickly increase as adolescence begins. Epidemiologic studies suggest that many of these children with migraine will continue to have headaches for many years.
The US Food and Drug Administration has encouraged research of new therapeutic agents in the pediatric age group. While the studies in migraine are proving newer agents safe, they have met challenges in proving efficacy because of high placebo response rates. This may be an artifactual issue related to study design and the clinical setting in which many teenagers treat their headaches, that is, at school. Early education of this age group in proper migraine therapy with medication and self-help techniques needs to be encouraged, and long-term studies of these efforts need to be conducted to determine the potential impact on altering the natural history of migraine.
By the time patients in their adult years have had migraine for a number of years, processes such as central sensitization and cutaneous allodynia become more common and the risk factors associated with lifestyle and comorbid medical and psychological illnesses may contribute to the potential for migraine's becoming increasingly refractive to treatment to both medications for acute attacks and to preventive therapy. Just having migraine over the course of years may in itself be a risk factor for this process. Early intervention in the acute attack of migraine may change the outcome if achieved before patients become allodynic. How this impacts the patient over the course of time has yet to be elucidated. Clinically, an attempt to reduce the overall frequency of migraine through preventive techniques appears to improve short-term therapeutic outcomes and may be beneficial for the long-term prognosis.
Although some patients with episodic migraine convert to a chronic stage each year, fewer revert from the chronic stage to episodic migraine. The reasons for these transitions to chronic headache are being understood with increasing clarity, but we can only surmise that improvements in quality of care and resolution of risk factors for chronic headache may play a role in such transitions.
Factors that play a role in the problem in migraine management include misdiagnosis. We need to consider overlap presentations, which may be driven by neuroanatomic issues, in our approach to patients with headache. Although some would tend to put all the patients with daily headaches into a single group, it is important to be able to clinically distinguish between them. We need to identify factors that contribute to the development of the daily headache and treat patients accordingly, as this approach by itself may allow for resolution of the daily headache phase. Additionally, therapeutics that work well for one disorder such as migraine may not work well for another such as tension-type headache including when the disorder becomes chronic, as seen in the work with botulinum toxin type A and other agents, as well.
Improvements in our ability to study migraine's pathophysiology and develop sound therapeutic approaches based on these studies may lead to altering the long-term prognosis for patients with this disorder. Migraine is the leading cause of painful disability in the United States in this age; yet, our appreciation for it often has been clouded by outmoded ideas of disease management and lack of understanding of optimal therapeutic utilization.
It is hoped that the concepts and information presented in this series of articles will enhance your knowledge of migraine and its treatment and improve the well-being of your patients.
Footnotes
Dr Freitag has received grants and/or conducted research for Abbott Laboratories; Allergan; AstraZeneca; Bristol-Myers Squibb; CAPNIA; Elan Pharmaceuticals; Eli Lilly and Company; EpiCept; GlaxoSmithKline; Merck & Co, Inc; Novartis; NPS Pharmaceuticals; and Ortho-McNeil Pharmaceuticals. He has served as a consultant to Abbott Laboratories; Allergan; AstraZeneca; Bristol-Myers Squibb; CAPNIA; Elan Pharmaceuticals, Inc; Eli Lilly and Company; EpiCept; GlaxoSmithKline; Interpharm Pharmaceuticals; Medpointe Pharmaceuticals; Merck & Co, Inc; Novartis; NPS Pharmaceuticals; Ortho-McNeil Pharmaceuticals; Pozen, Inc; Solvay Pharmaceuticals; and Xcel Pharmaceuticals. Dr Freitag has also served on the speakers bureau of Abbott Laboratories; AstraZeneca; Bristol-Myers Squibb; GlaxoSmithKline, Medpointe Pharmaceuticals; Merck & Co,Inc; Ortho-McNeil Pharmaceuticals; Pfizer Inc; and Xcel Pharmaceuticals.
This continuing medical education publication supported by an unrestricted educational grant from Merck & Co, Inc
Dr Freitag is associate director of the Diamond Headache Clinic in Chicago, Ill; an affiliate instructor in the Department of Family Medicine at Midwestern University's Chicago College of Osteopathic Medicine in Downers Grove, Ill; and a clinical associate professor in the Department of Family Medicine at Rosalind Franklin University of Medicine and Science/Chicago Medical School in North Chicago, Ill.
References
1. Living E. On Megrim, Sick Headache, and Some Allied Disorders: A Contribution to the Pathophysiology of Nerve-Storms. London, England: J and A Churchill; 1873:335 -395.
2. Wolff HG. Headache and Other Head Pain. New York, NY: Oxford University Press; 1948:261 -286.(Frederick G. Freitag, DO)