Migraine and Other Headache Disorders pdf

Migraine and Other
Headache Disorders
DK5905_half-series-title-02 4/3/06 1:33 PM Page A
NEUROLOGICAL DISEASE AND THERAPY
Advisory Board
Gordon H. Baltuch, M.D., Ph.D.
Department of Neurosurgery
University of Pennsylvania
Philadelphia, Pennsylvania, U.S.A.
Louis R. Caplan, M.D.
Professor of Neurology
Harvard University School of Medicine
Beth Israel Deaconess Medical Center
Boston, Massachusetts, U.S.A.
Mark A. Stacy, M.D.
Movement Disorder Center
Duke University Medical Center
Durham, North Carolina, U.S.A.
Mark H. Tuszynski, M.D., Ph.D.
Professor of Neurosciences
Director, Center for Neural Repair
University of California—San Diego
La Jolla, California, U.S.A.
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1. Handbook of Parkinson’s Disease,
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3. Familial Alzheimer’s Disease: Molecular Genetics and Clinical Perspectives,
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5. Therapy of Parkinson’s Disease,
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6. Handbook of Sleep Disorders,
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7. Epilepsy and Sudden Death,
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8. Handbook of Multiple Sclerosis,
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9. Memory Disorders: Research and Clinical Practice,
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10. The Medical Treatment of Epilepsy,
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11. Cognitive Disorders: Pathophysiology and Treatment,
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12. Handbook of Amyotrophic Lateral Sclerosis,
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13. Handbook of Parkinson’s Disease: Second Edition, Revised and Expanded,
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14. Handbook of Pediatric Epilepsy,
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15. Handbook of Tourette’s Syndrome and Related Tic and Behavioral Disorders,
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16. Handbook of Cerebellar Diseases,

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17. Handbook of Cerebrovascular Diseases,
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18. Parkinsonian Syndromes,
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19. Handbook of Head and Spine Trauma,
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36. Handbook of Neurotoxicology,
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38. Handbook of Autonomic Nervous System Dysfunction,
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Amos D. Korczyn
39. Handbook of Dystonia,
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40. Etiology of Parkinson’s Disease,
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41. Practical Neurology of the Elderly,
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48. Management of Acute Stroke,
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50. Handbook of Ataxia Disorders,
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56. Dopamine Receptors and Transporters: Function, Imaging,
and Clinical Implication, Second Edition,
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58. Handbook of Stereotactic and Functional Neurosurgery,
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59. Handbook of Parkinson’s Disease: Third Edition,
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62. Drug-Induced Movement Disorders,
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63. Therapy of Parkinson’s Disease: Third Edition, Revised and Expanded,
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64. Epilepsy: Scientific Foundations of Clinical Practice,
edited by Jong M. Rho,
Raman Sankar, and José E. Cavazos
65. Handbook of Tourette’s Syndrome and Related Tic and Behavioral Disorders:
Second Edition,
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66. Handbook of Cerebrovascular Diseases: Second Edition, Revised and Expanded,

edited by Harold P. Adams, Jr.
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75. Neurogenetics: Scientific and Clinical Advances,
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76. Epilepsy Surgery: Principles and Controversies,
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77. Clinician's Guide To Sleep Disorders,
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78. Amyotrophic Lateral Sclerosis,
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79. Duchenne Muscular Dystrophy: Advances in Therapeutics,
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80. Handbook of Multiple Sclerosis, Fourth Edition,
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81. Brain Embolism,
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82. Handbook of Secondary Dementias,
edited by Roger Kurlan
83. Parkinson's Disease: Genetics and Pathogenesis,
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84. Migraine,
Russell Lane and Paul Davies
85. Migraine and Other Headache Disorders,
edited by Richard B. Lipton
and Marcelo E. Bigal
DK5905_half-series-title 4/5/06 4:13 PM Page E

Richard B. Lipton
Albert Einstein College of Medicine
New York, New York, U.S.A.
Marcelo E. Bigal
Albert Einstein College of Medicine

New York, New York, U.S.A.
New York London
Migraine and Other
Headache Disorders
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Preface
With this first edition of Migraine and Other Headache Disorders, we celebrate the
remarkable progress in the art and science of headache during the last decade. With
32 chapters by 54 leaders in the field, the book provides health care professionals
with practical approaches to patient care and reviews the scientific foundations of
headache. We emphasize migraine because of its high prevalence, enormous burden,
and the increasing availability of effective management strategies. At the same time,
we provide broad coverage of all the primary headache disorders. Finally, although
not focusing on specific subtypes of secondary headaches, we discuss strategies for
diagnosing and excluding the ominous causes of headache, based both on clinical
evaluation and, when appropriate, the use of diagnostic testing.
Our understanding of headache and the approach to treatment have been
transformed by insights from many places. Based on the Second Edition of the Inter-
national Classification of Headache Disorders, the book provides a series of diagnos-
tic algorithms intended to simplify clinical practice. We also present up-to-date
epidemiologic information on the primary headache disorders. Epidemiologic stud-
ies show that the overwhelming majority of headache sufferers who seek treatment in
primary care settings have migraine. Diagnosis becomes more efficient when that
fact is taken into account. Doctors should avoid oversimplifying the differential
diagnosis of the primary headaches, however.
Our understanding of migraine as a disorder has significantly evolved over the
past decade, based on genetic, epidemiologic, and translational studies. Once consid-
ered an episodic pain problem, treating the pain seemed like a sensible strategy. In the
past few years, many lines of evidence hav e suggested that migraine and other head-
ache disorders are best understood as chronic disorders with episodic manifestations.

Painful episodes are the most prominent manifestation of migraine. Nonetheless,
between attacks, there is an enduring predisposition to headache that characterizes
the migraine brain. Furthermore, migraine is not only a chronic disorder with epi-
sodic manifestations, it is sometimes a disorder that progresses in several ways. Pro-
gression may be clinical, as attacks increase in frequency until chronic or transformed
migraine develops. This clinical progression is sometimes accompanied by the devel-
opment of allodynia with sensitization as its presumed substrate. In addition, in some
individuals, morphological progression takes the form of deep white matter lesion or
posterior circulation strokes that increase with migraine attack frequency, probably
reflecting neuroplastic changes in the brain. Herein we highlight the emerging data
on progression and on the modifiable risk factors for migraine progression.
Progress in treatment has also taken several forms. Since 1990, ten new acute
treatments with a multiplicity of formulations and two preventive drugs have been
iii
approved. Many studies show that acute treatments work best if given early in the
attack. Combining acute treatments may improve treatment response in some indi-
viduals. In addition, recent epidemiologic data shows that, based on frequency and
disability criteria, preventive treatment should be offered or considered in about
40% of migraine sufferers. The same studies show that only 12% currently receive
preventive therapy. Preventive treatment decreases attack frequency and severity
and possibly prevents migraine progression. The use of specific acute agents that
act on the neural pathways of migraine pain, such as the triptans, dramatically
improve patient out comes.
Migraine and Other Headache Disorders highlights the treatment approaches
developed at some of the best headache clinics in the worl d. It also reflects many
of the strategies adopted at The Montefiore Headache Center. The Montefiore
Headache Center was the first headache specialty care center in the world, founded
in 1945 by Dr. Arnold Friedman, and it is where we are both proud to be.
We are extremely grateful to our mentors. Among them, Dr. Lipton wants to
thank Dr. Seymour Solomon, who directed The Montefiore Headache Center for a

quarter of a century, for being a wonderful mentor and teacher. He’d also like to
thank his mentors and collaborators in research, particularly Drs. Philip Holzman,
W. Allen Hauser, and Walter F. Stewart. Dr. Bigal wants to acknowledge
Drs. Speciali and Bordini, from Brazil, and the teams at The New England Center
for Headache (Rapoport, Sheftell, and Tepper) and at M ontefiore (Lipton and
Solomon) for their help and direction. We also want to thank the authors of the
chapters in this book for their excellent work.
Finally, we owe special thanks to our families, particularly our wives (Amy
Natkins Lip ton and Janaı
´
na Maciel Bigal) and children (Lianna Lipton, Justin
Lipton, Luı
´
sa Bigal, and Hanna Bigal) for supporting us through evenings and week-
ends spent writing and editing as we prepared this book.
Finally, to our readers, we hope this book furthers your efforts to improve the
lives of headache sufferers. These common and disabling disorders are tremendously
gratifying to treat. In a field where cures are rare, we can none theless help patients by
empowering them with tools that relieve pain, restore their ability to function, and,
perhaps, prevent disease pro gression.
Richard B. Lipton
Marcelo E. Bigal
iv Preface
Contents
Preface . . . . iii
Contributors . . . . xv
1. Headache—Classification . . . . . . . . 1
Marcelo E. Bigal and Richard B. Lipton
Introduction . . . . 1
An Overview of the ICHD-2 . . . . 1

Classification of the Primary Headaches . . . . 5
Secondary Headaches . . . . 14
Headache Attributed to Head and/or Neck Trauma . . . . 14
Headache Attributed to Cranial or Cervical
Vascular Disorders . . . . 14
Headache Attributed to Nonvascular Intracranial Disorders . . . . 15
Headache Attributed to a Substance or Its Withdrawal . . . . 15
Headache Attributed to Infection . . . . 15
Headache Attributed to Disorders of Homeostasis . . . . 15
Headache or Facial Pain Attributed to Disorders of Cranium,
Neck, Eyes, Ears, Nose, Sinuses, Teeth, Mouth, or
Other Facial or Cranial Structures . . . . 16
Headache Attributed to Psychiatric Disorders . . . . 16
Cranial Neuralgias and Central Causes of Facial Pain . . . . 16
Controversies in the Classification of Primary Chronic Daily
Headaches of Long Duration . . . . 16
References . . . . 17
2. The Epidemiology and Impact of Migraine . . . 23
Richard B. Lipton and Marcelo E. Bigal
Introduction . . . . 23
The Epidemiology of Migraine . . . . 23
The Burden of Migraine . . . . 31
Probable Migraine—An Important Migraine Subtype . . . . 32
Conclusions . . . . 33
References . . . . 34
v
3. Progressive Headache: Epidemiology, Natural History, and
Risk Factors . . . 37
Ann I. Scher
Introduction . . . . 37

Classification . . . . 37
Chronic Daily Headache Epidemiology and Natural History . . . . 38
Demographic Factors Associated with Chronic
Daily Headache . . . . 38
Other Factors Associated with Chronic Daily Headache
Prevalence or Incidence . . . . 39
Conclusion . . . . 42
References . . . . 42
4. Comorbidity of Migraine . 45
Nancy C. P. Low and Kathleen Ries Merikangas
Introduction . . . . 45
Methodology of Comorbidity Studies . . . . 45
Evidence for Migraine Comorbidity . . . . 46
Conclusion . . . . 53
References . . . . 54
5. Pain Sensitivity: Intracranial and Extracranial Structures . . . . . . . . 61
Todd D. Rozen
Anatomy of Head Pain . . . . 61
References . . . . 65
6. Pathophysiology of Aura . 67
M. Sanchez del Rio and U. Reuter
Introduction . . . . 67
Neurophysiological Mechanisms . . . . 67
Imaging Studies . . . . 72
Molecular Mechanisms . . . . 72
Occipital Cortex Excitability . . . . 74
Genetics . . . . 75
Conclusions . . . . 76
References . . . . 77
7. Pathophysiology of Migraine . . . . . 81

Peter J. Goadsby
Introduction . . . . 81
Migraine—Explaining the Clinical Features . . . . 81
Genetics of Migraine . . . . 82
Familial Hemiplegic Migraine (FHM) . . . . 82
Migraine Aura . . . . 83
Headache—Anatomy . . . . 83
Headache Physiology—Peripheral Connections . . . . 84
vi Contents
Headache Physiology—Central Connections . . . . 86
Central Modulation of Trigeminal Pain . . . . 88
What Is Migraine? . . . . 89
References . . . . 90
8. Allodynia and Sensitization in Migraine . . . . . 99
William B. Young, Avi Ashkenazi, and Michael L. Oshinsky
Introduction . . . . 99
Sensory Processing by the Nervous System . . . . 100
Sensitization of the Dorsal Horn . . . . 100
Rat Model of Migraine Headache and Allodynia . . . . 102
Human Studies of Allodynia in Pain Disorders
Other Than Migraine . . . . 103
Human Studies of Allodynia in Migraine . . . . 104
Time Course of Sensitization in Migraine . . . . 106
The Effect of Allodynia on Treatment Outcome . . . . 106
The Effect of Treatment on Allodynia . . . . 107
Allodynia in Headache Disorders Other Than Migraine . . . . 107
Conclusion . . . . 108
References . . . . 108
9. Genetics of Migraine and Other Primary Headaches . . . 113
Gisela M. Terwindt, Esther E. Kors, Joost Haan, Kaate R. J. Vanmolkot,

Rune R. Frants, Arn M. J. M. van den Maagdenberg, and
Michel D. Ferrari
Introduction—Genetic Studies on Headache . . . . 113
The Clinical Spectrum of the CACNA1A Gene Mutations . . . . 114
The Clinical Spectrum of the ATP1A2 Gene . . . . 118
Sporadic Hemiplegic Migraine . . . . 120
Genetic Susceptibility in Migraine . . . . 120
Cluster Headache . . . . 123
Tension-Type Headache . . . . 123
Concluding Remarks . . . . 123
References . . . . 124
10. Identification or Exclusion of Secondary Headaches . . 131
Randolph W. Evans and R. Allan Purdy
Introduction . . . . 131
General Indications for Neuroimaging for Headaches . . . . 132
Neuroimaging for Headaches with a Normal
Neurological Examination . . . . 132
Neuroimaging for Migraine . . . . 133
Evaluation of the Acute Severe New-Onset Headache (‘‘First or
Worst Headaches’’) . . . . 135
Headaches Over the Age of 50 Years . . . . 138
New Daily Headaches . . . . 140
References . . . . 141
Contents vii
11. Differential Diagnosis of Primary Headaches:
An Algorithm-Based Approach . . . 145
Richard B. Lipton and Marcelo E. Bigal
Introduction . . . . 145
Approaching a Patient with Headache . . . . 145
Conclusions . . . . 152

References . . . . 152
12. Diagnostic and Severity Tools for Migraine . 155
Marcelo E. Bigal and Richard B. Lipton
Introduction . . . . 155
Screening for Migraine . . . . 156
Assessing Migraine-Related Disability . . . . 159
Assessing Psychological Comorbidity . . . . 163
Assessing Ongoing Treatment . . . . 163
Conclusion . . . . 165
References . . . . 165
Appendix: The PRIME-MD Questionnaire . . . . 167
13. Migraine Without Aura . 173
Fred Sheftell and Roger Cady
Introduction—Migraine Without Aura: An Underdiagnosed and
Undertreated Disorder . . . . 173
The ICHD-2 Criteria for Migraine Without Aura . . . . 174
Migraine in Clinical Practice . . . . 177
The Convergence Hypothesis . . . . 181
Menstrually Related Migraine . . . . 182
Conclusion . . . . 183
Illustrative Case History . . . . 184
References . . . . 184
14. Migraine with Aura . . . . 189
Malene Kirchmann Eriksen and Jes Olesen
Introduction . . . . 189
Classification . . . . 189
Migraine with Typical Aura . . . . 192
Familial and Sporadic Hemiplegic Migraine . . . . 197
Basilar-Type Migraine . . . . 198
Differential Diagnoses . . . . 199

References . . . . 199
15. Childhood Periodic Syndromes . . . 203
Vincenzo Guidetti, Federica Galli, Azzurra Alesini, and Federico Dazzi
Introduction . . . . 203
Cyclical Vomiting . . . . 204
RAP and Abdominal Migraine . . . . 206
BPV of Childhood . . . . 207
viii Contents
Benign Paroxysmal Torticollis . . . . 208
Alternating Hemiplegia of Childhood . . . . 209
Conclusion . . . . 209
References . . . . 210
16. Retinal, or ‘‘Monocular,’’ Migraine 213
Brian M. Grosberg and Seymour Solomon
Introduction . . . . 213
Diagnostic Criteria . . . . 213
Clinical Features . . . . 215
Epidemiology and Prognosis . . . . 217
Pathophysiology . . . . 218
Differential Diagnosis . . . . 218
Management . . . . 219
References . . . . 220
17. Status Migrainosus, Persistent Aura, Migraine-Associated Seizures
(‘‘Migralepsy’’), and Migrainous Infarction . . 223
Jessica Crowder, Curtis Delplanche, and John F. Rothrock
Introduction . . . . 223
Status Migrainosus . . . . 223
Prolonged Aura . . . . 227
Migralepsy . . . . 228
Migraine and Stroke . . . . 232

References . . . . 236
18. Principles of Headache Management . . . . . . 241
Marc S. Husid and Alan M. Rapoport
Introduction . . . . 241
Establishing the Diagnosis . . . . 242
Assessing Disability . . . . 252
Educating Patients . . . . 252
Establishing Realistic Expectations . . . . 254
Encouraging Patients to Become Active in Their Own Care . . . . 254
Headache Calendars . . . . 255
Developing an Appropriate, Individualized Treatment Plan . . . . 256
Why Headache Treatment Fails . . . . 256
Conclusion . . . . 257
References . . . . 258
Further Reading (Patient Education Resources) . . . . 258
Appendix 1 . . . . 260
19. Behavioral and Educational Approaches to the Management of Migraine:
Clinical and Public Health Applications . . . . 261
Kenneth A. Holroyd
Introduction . . . . 261
Behavioral Interventions . . . . 261
Contents ix
Treatment Delivery . . . . 263
Efficacy . . . . 264
Integrating Drug and Behavioral Treatments . . . . 265
Education for Self-Management . . . . 266
Community Applications . . . . 267
Conclusion . . . . 270
References . . . . 270
20. Nonspecific Migraine Acute Treatment . . . . 273

Abouch Krymchantowski and Stewart J. Tepper
Introduction . . . . 273
Simple Analgesics . . . . 274
Medications for the Treatment of Nausea . . . . 277
Combinations of NSAIDs and Triptans . . . . 278
Neuroleptics in the Treatment of Pain . . . . 279
OPIOIDS . . . . 279
Nonspecific vs. Specific Treatments . . . . 280
Conclusions . . . . 282
References . . . . 283
21. Specific Acute Migraine Treatment: Ergotamine and Triptans . . . . 289
Hans-Christoph Diener and Volker Limmroth
Introduction . . . . 289
Ergotamine . . . . 289
Ergotamine vs. Oral Triptans . . . . 290
Triptans . . . . 292
Conclusions . . . . 304
References . . . . 304
22. Preventive Treatment for Migraine 311
Stephen D. Silberstein
Introduction—Why and When to Use
Migraine-Preventive Medications . . . . 311
Mechanism of Action of Preventive Medications . . . . 313
Specific Migraine-Preventive Agents . . . . 315
Setting Treatment Priorities . . . . 345
References . . . . 347
23. Herbal Medicines and Vitamins . . . 363
Jean Schoenen and Delphine Magis
Introduction . . . . 363
Riboflavin . . . . 363

Coenzyme Q10 . . . . 366
Thioctic Acid (a-Lipoic Acid) . . . . 367
Feverfew (Tanacetum parthenium) . . . . 367
Butterbur (Petasites hybridus) . . . . 369
Magnesium . . . . 370
x Contents
Conclusions . . . . 370
References . . . . 371
24. Treatment of Migraine in Children and Adolescents . . . 375
Paul Winner
Introduction . . . . 375
Acute Treatment . . . . 376
Preventive Therapy . . . . 381
Conclusions . . . . 388
References . . . . 389
25. Inpatient Management and Invasive Treatment Strategies for Migraine
and Chronic Daily Headaches . . . . 393
Frederick G. Freitag
Introduction . . . . 393
Inpatient Treatment . . . . 393
Invasive Treatment of Migraine and Chronic
Daily Headaches . . . . 405
Conclusion . . . . 408
References . . . . 409
26. Migraine in the Emergency Department . . . . 413
Merle Diamond and Benjamin W. Friedman
Introduction . . . . 413
How to Approach a Patient with Acute Headache in the ED . . . . 414
Treatment . . . . 417
Specific Situations . . . . 422

Disposition . . . . 423
Status Migrainosus/Intractable Pain . . . . 425
References . . . . 426
27. Progression Forms of Migraine . . . 431
Marcelo E. Bigal and Richard B. Lipton
Introduction . . . . 431
Epidemiology of the CDH
S 432
Transformed Migraine . . . . 432
Prospects for Preventing Headache Progression . . . . 441
References . . . . 442
28. The Future of Migraine Therapies . 445
Todd Schwedt and David Dodick
Introduction . . . . 445
Trigeminal Receptor Targets . . . . 446
Adenosine Receptors . . . . 448
Drugs Targeting the ORL-1 Receptors . . . . 448
Vanilloid Receptors . . . . 449
Contents xi
Glutamate Receptors . . . . 449
CGRP Receptor Antagonists . . . . 450
NOS Inhibitors . . . . 450
Pharmacogenomics . . . . 451
Summary . . . . 452
References . . . . 453
29. Tension-Type Headache . 457
Rigmor Jensen
Introduction . . . . 457
The Epidemiology of TTH . . . . 458
The Clinical Presentation of TTH . . . . 460

Physical Examination in Subjects with TTH . . . . 462
Psychological Aspects of TTH . . . . 463
Pathophysiology . . . . 463
Treatment . . . . 464
References . . . . 465
30. Trigeminal Autonomic Cephalgias . 471
David Dodick
Introduction . . . . 471
Pathophysiology . . . . 471
Cluster Headache . . . . 473
Paroxysmal Hemicranias . . . . 484
SUNCT Syndrome . . . . 486
References . . . . 487
31. Other Primary Headaches . . . . . . 495
Lawrence C. Newman, Susan W. Broner, and Christine L. Lay
Introduction . . . . 495
Primary Stabbing Headache (ICHD-2 Code 4.1) . . . . 495
Primary Cough Headache (ICHD-2 Code 4.2) . . . . 496
Primary Exertional Headache (ICHD-2 Code 4.3) . . . . 497
Primary Headaches Associated with Sexual Activity
(ICHD-2 Code 4.4) . . . . 498
The Hypnic Headache Syndrome (ICHD-2 Code 4.5) . . . . 499
Primary Thunderclap Headache (ICHD-2 Code 4.6) . . . . 500
Hemicrania Continua (ICHD-2 Code 4.7) . . . . 501
New Daily-Persistent Headache (ICHD-2 Code 4.8) . . . . 503
Conclusion . . . . 505
References . . . . 505
32. When the Treatment of Headache Fails . . . . 509
Richard B. Lipton and Marcelo E. Bigal
Introduction . . . . 509

Reason 1: The Diagnosis Is Incomplete or Incorrect . . . . 509
xii Contents
Reason 2: Important Exacerbating Factors
May Have Been Missed . . . . 514
Reason 3: Pharmacotherapy May Be Inadequate . . . . 515
Reason 4: Nonpharmacologic Treatment
May Be Inadequate . . . . 517
Reason 5: Other Reasons for Treatment Failure . . . . 517
Conclusions . . . . 518
References . . . . 518
Index . . . . 523
Contents xiii

Contributors
Azzurra Alesini Department of Child and Adolescent Neurology and Psychiatry,
University of Rome La Sapienza, Rome, Italy
Avi Ashkenazi Department of Neurology, Jefferson Headache Center,
Thomas Jefferson University, Philadelphia, Pennsylvania, U.S.A.
Marcelo E. Bigal Department of Neurology, Albert Einstein College of Medicine,
The Montefiore Headache Center, New York, New York, and The New England
Center for Headach e, Stamford, Connecticut, U.S.A.
Susan W. Broner The Headache Institute, Roosevelt Hospital Center, New York,
New York, U.S.A.
Roger Cady Headache Care Center, Primary Care Network, Springfield,
Missouri, U.S.A.
Jessica Crowder Department of Neurology, University of South Alabama
College of Medicine, Mobile, Alabama, U.S.A.
Federico Dazzi Department of Child and Adolescent Neurology and Psychiatry,
University of Rome La Sapienza, Rome, Italy
Curtis Delplanche Department of Neurology, University of South Alabama

College of Medicine, Mobile, Alabama, U.S.A.
M. Sanchez del Rio Department of Neurology, Headache Program,
Hospital Ruber Inter national, Madrid, Spain
Merle Diamond Diamond Headache Clinic and Rosalyn Finch School of Medicine,
Chicago, Illinois, U.S.A.
Hans-Christoph Diener Department of Neurology, University of Duisburg-Essen,
Essen, Germany
David Dodick Mayo Clinic College of Medicine, Scottsdale, Arizona, U.S.A.
xv
Malene Kirchmann Eriksen Department of Neurology, The Danish Headache
Center, University of Copenhagen, Glostrup Hospital, Copenhagen, Denmark
Randolph W. Evans Department of Neurology and Neuroscience, Weill Medical
College of Cornell University, New York, New York, Department of Neurology,
The Methodist Hospital, and Baylor College of Medicine, Houston, Texas, U.S.A.
Michel D. Ferrari Department of Neurology, Leiden University Medical Center,
Leiden, The Netherlands
Rune R. Frants Department of Human Genetics, Leiden University Medical
Center, Leiden, The Netherlands
Frederick G. Freitag Diamond Headache Clinic, Chicago and Department of
Family Medicine, Chicago College of Osteopathic Medicine, Downers Grove and
Department of Family Medicine, Rosalind Franklin University of Medicine and
Science/Chicago Medical School, North Chicago, Illinois, U.S. A.
Benjamin W. Friedman Department of Emergency Medicine, Albert Einstein
College of Medicine, The Montefiore Headache Center, New York, New York,
U.S.A.
Federica Galli Department of Child and Adolescent Neurology and Psychiatry,
University of Rome La Sapienza, Rome, Italy
Peter J. Goadsby Institute of Neurology, The National Hospital for Neurology
and Neurosurgery, Queen Square, London, U.K.
Brian M. Grosberg Department of Neurology, The Montefiore Headache Center,

Albert Einstein College of Medicine, New York, New York, U.S.A.
Vincenzo Guidetti Department of Child and Adolescent Neurology and Psychiatry,
University of Rome La Sapienza, Rome, Italy
Joost Haan Department of Neurology, Leiden University Medical Center, Leiden,
and Department of Neurology, Rijnland Hospital, Leiderdorp,
The Netherlands
Kenneth A. Holroyd Psychology Department, Ohio University, Athens,
Ohio, U.S.A.
Marc S. Husid Department of Neurology, Walton Headache Center,
Medical College of Georgia, Augusta, Georgia, U.S.A.
Rigmor Jensen Department of Neurology, The Danish Headache Center,
University of Copenhagen, Glostrup Hospital, Glostrup, Denmark
Esther E. Kors Department of Neurology, Leiden University Medical Center,
Leiden, The Netherlands
xvi Contributors
Abouch Krymchantowski Outpatient Headache Unit, Instituto de Neurologia, and
Deolindo Couto, Headache Center of Rio, Rio de Janeiro, Brazil
Christine L. Lay The Headache Institute, Roosevelt Hospital Center, New York,
New York, U.S.A.
Volker Limmroth Department of Neurology, Cologne City Hospitals,
University of Cologne, Cologne, Germany
Richard B. Lipton Departments of Neurology, Epidemiology and Population
Health, Albert Einstein College of Medicine, and The Montefiore Headache Center,
New York, New York, U.S.A.
Nancy C. P. Low Section on Developmental Genetic Epidemiology, Mood and
Anxiety Disorders Program, Intramural Research Program, National Institute of
Mental Health, National Institutes of Health, Department of Health and Human
Services, Bethesda, Maryland, U.S.A.
Delphine Magis Departments of Neuroanatomy and Neurology, Headache
Research Unit, University of Lie

`
ge, Lie
`
ge, Belgium
Kathleen Ries Merikangas Section on Developmental Genetic Epidemiology,
Mood and Anxiety Disorders Program, Intramural Research Program, National
Institute of Mental Health, National Institutes of Health, Department of Health and
Human Services, Bethesda, Maryland, U.S.A.
Lawrence C. Newman The Headache Institute, Roosevelt Hospital Center,
New York, New York, U.S.A.
Jes Olesen Department of Neurology, The Danish Headache Center, University of
Copenhagen, Glostrup Hospital, Copenhagen, Denmark
Michael L. Oshinsky Department of Neurology and Preclinical Research, Jefferson
Headache Center, Thomas Jefferson University, Philadelphia, Pennsylvania, U.S.A.
R. Allan Purdy Division of Neurology, Dalhousie University, and Queen
Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada
Alan M. Rapoport The New England Center for Headache, Stamford, Connecticut,
and Department of Neurology, Columbia University College of Physicians and
Surgeons, New York, New York, U.S.A.
U. Reuter Department of Neurology, Charite
´
, Universita
¨
tsmedizin Berlin,
Berlin, Germany
John F. Rothrock Department of Neurology, University of South Alabama
College of Medicine, Mobile, Alabama, U.S.A.
Todd D. Rozen Department of Neurol ogy, Michigan Head Pain and Neurological
Institute, Ann Arbor, Michigan, U.S.A.
Contributors xvii

Ann I. Scher Department of Preventive Medicine and Biometrics, Uniformed
Services University of the Health Sciences, Bethesda, Maryland, U.S.A.
Jean Schoenen Departments of Neuroanatomy and Neurology, Headache
Research Unit, University of Lie
`
ge, Lie
`
ge, Belgium
Todd Schwedt Department of Neurology, The Cleveland Clinic Foundation,
Cleveland, Ohio, U.S.A.
Fred Sheftell The New England Center for Headache, Stamford,
Connecticut, U.S.A.
Stephen D. Silberstein Department of Neurology, Jefferson Headache Cent er,
Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, U.S.A.
Seymour Solomon Department of Neurology, The Montefiore Headache Center,
Albert Einstein College of Medicine, New York, New York, U.S.A.
Stewart J. Tepper The New England Center for Headache, Stamford, and
Department of Neu rology, Yale University School of Medicine, New Haven,
Connecticut, U.S.A.
Gisela M. Terwindt Department of Neurology, Leiden University Medical Center,
Leiden, The Netherlands
Arn M. J. M. van den Maagdenberg Department of Neurology and Human
Genetics, Leiden University Medical Center, Leiden, The Netherlands
Kaate R. J. Vanmolkot Department of Human Genetics, Leiden University
Medical Center, Leiden, The Netherlands
Paul Winner Palm Beach Headache Center, and Nova Southeastern University,
Fort Lauderdale, Florida, U.S.A.
William B. Young Department of Neurology and Inpatient Program, Jefferson
Headache Center, Thomas Jefferson University, Philadelphia, Pennsylvania, U.S.A.
xviii Contributors