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KEY POINT: A The largest obstacle to designing a functional headache classification is the lack of reliable diagnostic...

Author: Morris Levin et al.

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KEY POINT:

A

The largest obstacle to designing a functional headache classification is the lack of reliable diagnostic tests for even such thoroughly studied illnesses as migraine and cluster headache.

CLASSIFICATION OF PRIMARY HEADACHES: CONCEPTS AND CONTROVERSIES Morris Levin

ABSTRACT Designing a comprehensive and practical classification schema for headache disorders has been an elusive goal for many reasons. The International Classification of Headache Disorders, 2nd Edition (ICHD-II) is the best attempt to date, but it, like its predecessor the ICHD-I, is plagued with a number of limitations. It was designed as both a research and clinical tool but can be frustrating for practitioners in either area. Primary headaches, such as migraine, chronic daily headache, and ‘‘other’’ headaches, such as new daily persistent headache, are particularly problematic sections of the classification. In addition, classification of a number of more complex (ie, where pathophysiology is poorly understood) secondary headaches, such as medication overuse and posttraumatic headaches, is also vexing. This chapter is an attempt to summarize the ICHD-II, focusing on primary headache types, and suggest best practices for usage of it.

INTRODUCTION

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Why Headache Classification? To properly study and effectively treat the various headache disorders, they must somehow be sorted. Arguably, the largest obstacle to designing a functional headache classification is the lack of reliable diagnostic tests for even such thoroughly studied illnesses as migraine and cluster headache. Any diagnostic system will therefore have to rely on subjective data, hence the descriptive approach to all headache classifications to date. In a rather circular type of logic, the only way to improve upon the methods of dividing various headache types is to subject the classification system itself to systematic study. To learn more about headaches, they must first be separated into more or less discrete categories,

then examined with the best tools available, next rearranged into more accurate categories based on evidence accumulated in this way, then reexamined, and so on. A number of pitfalls are easily encountered. First, there is the risk of making the classification too specific— the tendency of ‘‘splitters.’’ The ‘‘lumper’’ approach is equally fraught with risks. When categories are too broad, the results of analysis can be all but unusable since conclusions may be so general as to apply to virtually no individuals. Another large problem is to decide where to establish demarcations between diagnostic categories in the absence of evidence (ie, most of the time). Here, the opinions of experts are taken into account. But which experts? And the experts do often disagree. Another problem is

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

the reasonable assumption that most headache patients generally have one illness. This, however, may not be the result when applying a diagnostic schema based on morphological features that can occur with several headache types, leading to multiple diagnoses. On these grounds and others, the ICHD classifications (Headache Classification Subcommittee of the International Headache Society, 2004; Headache Classification Subcommittee of the International Headache Society, 1988) have been criticized (Bigal et al, 2004; Leone et al, 1998; Manzoni and Torelli, 2004; Olesen and Rasmussen, 1996; Pearce, 1996; Silberstein et al, 1995; Silberstein et al, 1994; Winner et al, 1997). Still, without a headache classification, research on pathophysiology, genetics, and treatment of headache disorders is essentially impossible. In addition, patients expect a diagnosis and prior to ICHD might well have received a different one from each physician they saw. Fields such as headache, where attempts at classification are evidence based, are those where the most efficient scientific progress is occurring. This chapter will focus on key areas of the ICHD classification of primary headaches rather than an exhaustive exploration of the 45 diagnostic entities contained therein. Tables for reference will be highlighted, and clinical examples of important diagnostic entities will be presented. Controversial areas as well as suggested revisions to the ICHD-II will be discussed. History of Classification Systems in Headache Headache classification began (as far as we know) with Aretaeus of Cappadocia in the first century, who divided headaches into cephalea (chronic, frequent, severe, long-lasting headaches) and cephalalgia (infrequent milder head-

aches). Thomas Willis, a founder of modern neurological thought, described in De Cephalalgia in 1672 headaches as ‘‘within or without the skull; universal or particular; short, continuous or intermittent; wandering or uncertain; before, behind or the side; and occasional or habitual.’’ Christian Baur in 1787 divided headaches into primary headaches (‘‘idiopathic’’) and secondary headaches (‘‘symptomatic’’), with a total of 84 categories, most of which have not withstood the test of time (Gladstone and Dodick, 2004; Isler, 1993; Pearce, 1986). The first significant modern attempt at classifying headache disorders was done by an ad hoc committee formed by the National Institutes of Health in 1962, which consisted of prestigious American thinkers in headache: Arnold Friedman, Knox Finley, John Graham, Charles Kunkle, Adrian Ostfeld, and Harold Wolff (Ad Hoc Committee on Classification of Headache of the National Institute of Health, 1962). This classification (Table 2-1) consisted of brief glossary-type definitions of a limited number of headache types. With its relatively vague diagnosis definitions, it required subjective interpretation and relied primarily on accepted ideas of headache diagnostic classes without much in the way of evidence to support them. This classification system, notable for strict differentiation between migraine headaches (pulsatile unilateral headaches with a vascular pathology) and tension headaches (with muscular pathophysiology) became accepted worldwide but by the 1970s began to be seen as more of an impediment than a help to advancing headache understanding. The International Headache Society (IHS), formed in 1982, embarked upon the task of classification by forming a classification committee in 1985 with Dr. Jes Olesen as the chairman. The IHS classification system was published


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" CLASSIFICATION OF PRIMARY HEADACHES

KEY POINT:

A

The effects of the International Classification of Headache Disorders were dramatic. It served to drive massive amounts of headache research, unified headache clinicians and researchers worldwide, and made a major first step in providing much-needed credibility and scientific rigor for the field of headache.

TABLE 2-1 Ad Hoc Committee on Classification of Headache of the National Institute of Health: Classification of Headache 1. Vascular headache A. Classic migraine B. Common migraine C. Cluster D. Hemiplegic, ophthalmoplegic migraine E. Lower-half headache 2. Muscle contraction headache 3. Combined headache: vascular and muscle contraction headache 4. Headache of nasal vasomotor reaction 5. Headache of delusional, conversion, or hypochondriacal states 6. Nonmigrainous vascular headaches 7. Traction headache 8. Headache due to overt cranial inflammation 9–13. Headache due to diseases of ear, nose, sinus, teeth 14. Cranial neuritides

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15. Cranial neuralgias Reprinted with permission from Ad Hoc Committee on Classification of Headache of the National Institute of Health. Classification of headache. JAMA; 1992;179:717–718. Copyright # 1992, American Medical Association. All rights reserved.

in 1988 (Headache Classification Committee of the International Headache Society, 1988). It was 96 pages long and consisted of 165 diagnoses. The effects of the ICHD were dramatic. It served to drive massive amounts of headache research, unified headache clinicians and researchers worldwide (it was trans-

lated into all major languages), and made a major first step in providing much-needed credibility and scientific rigor for the field of headache. In addition, a correspondence to the International Classification of Diseases of the World Health Organization further enabled uniformity and accuracy in diagnosis. The revision of the IHS classification was begun in 1999 (it had actually been planned for revision in 1993). After attempts were made to obtain input from headache and other specialists and a limited number of prepublication presentations occurred, the ICHD-II was published in Cephalalgia in January 2004 (Headache Classification Subcommittee of the International Headache Society, 2004). The ICHD-II is 160 pages long and contains approximately 200 diagnoses.

ICHD-II—BASIC ORGANIZATION Format The ICHD-II, like its predecessor, consists of several parts (Table 2-2). This edition includes the following: Part 1: primary headaches; Part 2: secondary headaches; Part 3: cranial neuralgias, central and primary facial pain and other headache; and the Appendix. Part 1, primary headaches, consists of 45 diagnostic categories in chapters 1 through 4 and includes migraine, tension-type headache, cluster headache and its relatives, and a group of ‘‘other primary headaches.’’ The first four groups are considered to have ‘‘no other causative disorder.’’ Part 2, secondary headaches, consists of 120 diagnostic categories in chapters 5 through 12 and includes headaches ‘‘caused by another disorder,’’ such as head trauma, vascular disease, abnormal intracranial pressure, mass lesions, hydrocephalus, and so on. These chapters also describe headaches


TABLE 2-2

International Classification of Headache Disorders Revised

Part 1: Primary Headaches, Chapters 1 Through 4 (No Other Causative Disorder) 1. Migraine 2. Tension-type headache 3. Cluster and its relatives (trigeminal autonomic cephalalgias) 4. Other primary headaches— exertional, hemicrania continua, hypnic headache, et al

due to processes involving a number of structures in and around the head, including the eyes, nose, sinuses, teeth, and neck. In addition, a brief chapter on headaches presumably caused by psychiatric disorders is included. Part 3 consists of 29 causes of facial pain or neuralgic illnesses as well as chapter 14, ‘‘empty for now,’’ to serve as something of a placeholder for any unclassifiable headache types. The appendix (Table 2-3) is an intriguing collection of suggested criteria for possible new entities, alternative diagnostic criteria for certain existing categories, and previously accepted

Part 2: Secondary Headaches, Chapters 5 Through 12 (Caused by Another Disorder) 5. Posttraumatic 6. Vascular disease 7. Other intracranial pathology, eg, abnormal intracranial pressure, neoplasm, hydrocephalus 8. Substances 9. Central nervous system infection 10. Homeostatic disorders, eg, hypoxia, hypertension, thyroid dysfunction 11. Cervicogenic; eyes; ears, nose, and throat; sinuses, mouth, teeth, temporomandibular joint 12. Psychiatric Part 3: Cranial Neuralgias, Central and Primary Facial Pain, Other Headaches 13. Neuralgias and neuropathy 14. Other headaches (no subheadings for now) Appendix Data from Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders: 2nd edition. Cephalalgia 2004;24(suppl 1):9–160.

International Classification of Headache Disorders, 2nd Edition, Appendix Contents

TABLE 2-3

1. Suggested criteria for possible new entities: For example, A1.1 Menstrual migraine A3.3 SUNA (short-lasting unilateral neuralgiform headache attacks with autonomic symptoms) 2. Alternative diagnostic criteria for certain categories (pending evidence): For example, A2 Two alternative tension-type headache diagnostic criteria 3. Some previously accepted disorders that have not been supported by evidence: For example, A.1.3.4 Alternating hemiplegia of childhood Data from Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders: 2nd edition. Cephalalgia 2004;24(suppl 1):9–160.


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KEY POINTS:

A

A

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Decisions about diagnoses and diagnostic criteria were made by International Headache Society subcommittees based on evidence, when possible, and expert opinion (consensus) when no evidence was available. In patients with more than one distinct type of headache, each headache type is coded separately.

related disorders, short descripdisorders that have not been suptions, explicit diagnostic criteria, ported by evidence. The appendix is notes and comments thus a list of fertile research topics and a vehicle for eventual incorporation of o Bibliography for the entire chapter with breakdown by subcategory new evidence into the next revision of the ICHD. For a particular diagnosis, all criteria Decisions about diagnoses and diag- must be fulfilled. Thus, to be considnostic criteria were made by the vari- ered orgasmic headache, 4.4.2, all of ous subcommittees based on evidence, the following must be true: when possible, and expert opinion A. Sudden severe (‘‘explosive’’) (consensus) when no evidence was headache available. (The choice of experts is an B. Occurs at orgasm obvious area of controversy.) C. Not attributed to another disorder A troublesome, but unavoidable In patients with more than one discomponent of the ICHD is that the tinct type of headache, each is coded definitions for headache disorders are separately, ie, a patient’s headache may symptom based for primary headaches, but etiology based for second- be coded as: ary headaches (which will presumably 1. 1.1 Migraine without aura, change when etiologies for primary 2. 2.2 Frequent episodic tension type headache, and headaches become known). 3. 8.2 Medication overuse headache Specificity in diagnosis is weighted higher than sensitivity. Precise incluIf a single headache type fulfills two sion and exclusion criteria for each different sets of explicit criteria, the use diagnosis are enumerated. The classifi- of other data is recommended, eg, hiscation is hierarchical, with a decimal tory of headache onset, family history, system for subdivision. For example, in menstrual relationship. the case of 5.2.2, chronic posttraumatic The classification of a patient’s headheadache attributed to mild head ache is based upon his or her current injury, 5 denotes posttraumatic head- phenomenology, or at least that occurache, 5.2 denotes chronic posttraumatic ring during the last year. This is a bit headache, and 5.2.2 denotes that this problematic since, for example, if the chronic posttraumatic headache was patient experienced different headache caused by mild head injury. types in the past, eg, migraine with The hierarchical format allows one to aura several years ago, the implication decide how detailed to make the may be drawn that the patient may diagnosis. The classification committee have the ‘‘trait’’ for migraine with aura. felt that in primary care settings, one to These considerations may be importwo digits of specificity would be useful tant in clinical as well as in research (eg, migraine without aura, 1.1) and that settings. for a researcher or specialist, a threeSecondary headaches (Part 2) should digit diagnosis would be more appro- begin to occur close in time to the priate (eg, typical aura with nonmigraine, causative disorder and disappear when 1.2.2). the cause is removed. The problem is Each chapter is organized with a that the cause may not be possible to standard order of information: eliminate. For these ambiguous situations, the ICHD encourages the use o General introduction of ‘‘probable’’ until further clarificao Subcategories, each including discussion of previously used terms, tion may be obtained (see below).


Nomenclature Chronic refers to frequency for some of the primary headache disorders— eg, chronic migraine and chronic tensiontype headache occur on more than 50% of days. But in cluster headache and paroxysmal hemicrania, ‘‘chronic’’ denotes the pattern of continuous vulnerability to individual attacks, eg, chronic cluster, as opposed to the more typical recurring cluster or hemicrania cycles (episodic). Finally, as is more typical in other pain terminology, ‘‘chronic’’ denotes the duration of the problem, eg, greater than 3 months for secondary headaches such as chronic posttraumatic headache. Aura is used for the well-described brief preheadache symptoms of migraine with aura and premonitory symptoms for the 2- to 48-hour period of forewarning before a migraine. The terms prodrome and warning symptoms are not used. Probable is the term used ubiquitously to indicate that generally all but one criterion has been met for a

particular diagnosis. For example, if a patient has recurrent headaches that seem ‘‘migrainous’’ (old term used in the ICHD-I) but fail to fulfill one of the four criteria for migraine, 1.6, probable migraine is used in place of migraine without aura, 1.1. Attributed to replaces the ‘‘associated with’’ phrase used for secondary headaches in ICHD-I to imply a causal link between the underlying disorder and the headache. (The problem of proving causality will lead to frequent ‘‘probable’’ secondary headache diagnoses.) All of the primary headache criteria include the requirement that the headache not be attributed to another disorder. Thus, in patients where doubt exists, two diagnoses are likely—a probable primary headache disorder as well as a probable secondary headache (Case 2-1).

KEY POINT:

A

All of the primary headache criteria include the requirement that the headache not be attributed to another disorder. Thus, in patients where there is doubt, two diagnoses are likely—a probable primary headache disorder as well as a probable secondary headache.

GENERAL MODELS FOR PRIMARY HEADACHES The generally held concepts of migraine, tension-type headache, and

Case 2-1 Headaches Following Trauma A 28-year-old man describes a recurrent syndrome of posterior headache pain. Although it may occur spontaneously, the headache can be induced by coughing or sneezing. The pain can last between several minutes and several hours. He remembers that these began in high school after he played in a ‘‘rough’’ football game and sustained a minor head injury (without concussion). Nausea is generally absent, but he states he sometimes gets ‘‘queasy.’’ Sexual intercourse does not induce headache. Medication, including indomethacin, has failed to relieve his headaches. His examination is entirely normal. Magnetic resonance imaging (MRI) scan reveals mild to moderate cerebellar tonsillar herniation. Comment. The obvious problem is to determine whether this young man’s headaches represent a primary headache disorder or are, instead, due to an Arnold Chiari malformation. According to the ICHD-II classification, headache attributed to Chiari malformation can be assigned only if the headaches disappear following surgical correction. Until then, one could use the ‘‘probable’’ diagnosis. The history of head trauma is intriguing as well, perhaps suggesting an additional secondary headache due to head trauma. New daily persistent headache (NDPH) is another possibility but would be difficult to support in the presence of a suspected instigating factor.


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cluster headache have been maintained in the ICHD-II. As would be expected, however, borderlands between them have been sacrificed. Some headaches are grouped into the cluster headache chapter (ICHD-II chapter 3) without clear linkage to cluster headache (eg, short duration, unilateral, neuralgic, conjunctival injection, and tearing [SUNCT]). ICHD-II chapter 4, Other Primary Headaches, includes many headaches that are not necessarily related to one another (eg, cough headache, hypnic headache, hemicrania continua, and NDPH). Hence, boundaries can be seen as arbitrary and not implying shared or similar causation. The one unifying feature to primary headaches is their unknown link to any other disease process. However, this begs the question of how to conceive of such things as typical ‘‘migrainoid’’ or cluster headaches newly occurring in the setting of a systemic illness or postulated secondary cause. Again, classifications force distinctions that at best may not be significant or at worst may be quite misleading. Neuralgias are presented in a completely separate part of the classification, although a case can be made that some of these fulfill the spirit of the concept of primary headache disorder. And this section contains symptomatic neuralgias such as Tolosa Hunt syndrome and postherpetic neuralgia, which can properly be considered secondary headache disorders. MIGRAINE AND ITS RELATIVES Migraine diagnosis depends on a relatively complex set of criteria (Table 2-4). In practice, the diagnosis is not difficult, but a number of patients with migraine will likely receive the diagnosis of probable migraine if ICHD criteria are strictly applied. Commonly reported migraine accompaniments such as nausea and light and sound sensitivity are expected criteria, but exercise

International Classification of Headache Disorders, 2nd Edition, 1.1 Migraine Without Aura

TABLE 2-4

A. At least five attacks fulfilling criteria B through D B. Headache attacks lasting 4 to 72 hours (untreated or unsuccessfully treated) C. Headache has at least two of the following characteristics: 1. Unilateral location 2. Pulsating quality 3. Moderate or severe pain intensity 4. Aggravation by or causing avoidance of routine physical activity (eg, walking or climbing stairs) D. During headache at least one of the following: 1. Nausea and/or vomiting 2. Photophobia and phonophobia E. Not attributed to another disorder Data from Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders: 2nd edition. Cephalalgia 2004;24(suppl 1):9–160.

intolerance, pulsation, and unilaterality are believed by many to be much less significant clues. Moderate or severe pain intensity is rather broad, and the requirement for both photosensitivity and phonosensitivity seems rather stringent to some. The migraine with aura category, 1.2, includes the odd-sounding terms aura with migraine, aura with nonmigraine, and aura without headache (Tables 2-5 and 2-6). The rationale behind this classification was to find a consistent way to evaluate the unusual patient


KEY POINT:

International Classification of Headache Disorders, 2nd Edition, 1.2 Migraine With Aura—Subtypes

TABLE 2-5

1.2.1 Typical aura with migraine headache 1.2.2 Typical aura with nonmigraine headache 1.2.3 Typical aura without headache 1.2.4 Familial hemiplegic migraine 1.2.5 Sporadic hemiplegic migraine 1.2.6 Basilar-type migraine Data from Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders: 2nd edition. Cephalalgia 2004;24(suppl 1):9–160.

with typical aura but whose headache type otherwise did not meet migraine criteria. It is very conceivable to assign tension-type headache, 2.1, and aura with nonmigraine, 1.2.2, to the same patient. Most examiners would consider the aura proof of migraine pathophysiology, and hence this begs the question of whether migraine criteria are too strict. Motor auras are placed in the separate hemiplegic migraine categories with the implication that motor auras are different from other auras, a concept suggested, although certainly not proven, by genetic studies of hemiplegic migraine (Carrera et al, 2001; De Fusco et al, 2003). Still, the criteria for the migraine chapter seem useful and do distinguish significant subtypes (Eriksen et al, 2004). As stated above, migrainelike headaches that meet all criteria save one are best termed probable migraine. Ophthalmoplegic migraine, once felt to be a primary headache, is now relegated to the neuralgia section

A TABLE 2-6 International Classification of Headache Disorders, 2nd Edition, 1.2.1 Typical Aura With Migraine Headache A. At least two attacks fulfilling criteria B through D B. Aura consisting of at least one of the following, but no motor weakness:

Motor auras are placed in the separate hemiplegic migraine categories with the implication that motor auras are different from other auras.

1. Fully reversible visual symptoms including positive features (eg, flickering lights, spots, or lines) and/or negative features (eg, loss of vision) 2. Fully reversible sensory symptoms including positive features (eg, pins and needles) and/or negative features (eg, numbness) 3. Fully reversible dysphasic speech disturbance C. At least two of the following: 1. Homonymous visual symptoms and/or unilateral sensory symptoms 2. At least one aura symptom develops gradually over 5 minutes and/or different aura symptoms occur in succession over 5 minutes 3. Each symptom lasts 5 and 60 minutes D. Headache fulfilling criteria B through D for 1.1 Migraine without aura begins during the aura or follows aura within 60 minutes E. Not attributed to another disorder Data from Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders: 2nd edition. Cephalalgia 2004;24(suppl 1):9–160.


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KEY POINT:

A

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There is no diagnostic category that applies to the oftenencountered patient with previous intermittent migraine who evolves to a condition with frequent headaches, many of which have minimal migraine features.

(13.17) based on suggestive evidence that the entity is more closely related to neuralgic syndromes. Basilar (type) migraine and retinal migraine are listed in the migraine chapter, however. Basilar migraine should have symptoms and or signs suggestive of the posterior cerebral circulation, such as bilateral visual symptoms, dysarthria, vertigo, hearing loss, diplopia, or ataxia (Table 2-7). Retinal migraine, of course, requires symptoms referable to one eye. Primary chronic daily headache, defined as headaches on 15 or more days per month (not due to underlying systemic or cranial pathology), is clearly an important public health problem with a surprisingly high prevalence— probably 4% worldwide. This category consists of a mixture of several disorders, including a chronic form of migraine, chronic tension-type headache, hemicrania continua, and NDPH. Chronic migraine, 1.5.1, requires that all headaches meet criteria for migraine (Table 2-8). Many objections have been made to this requirement for chronic migraine since there is thus no diagnostic category that applies to the often-encountered patient with previous intermittent migraine who evolves to a condition with frequent headaches, many of which have minimal migraine features (Case 2-2). This condition was initially termed transformed migraine by Mathew in 1982 and was included by Silberstein and Lipton in their commonly accepted classification of chronic daily migraine (Mathew et al, 1982; Silberstein et al, 1994) (Table 2-9). So where do these patients fit in the ICHD-II? Most, by virtue of the fact that migrainous features are sparse, will receive the ICHD diagnosis of chronic tension-type headache. Those who have been using frequent antiheadache medication will also, or instead, be diagnosed as probable

International Classification of Headache Disorders, 2nd Edition, 1.2.6 Basilar-type Migraine

TABLE 2-7

A. At least two attacks fulfilling criteria B through D B. Aura consisting of at least two of the following fully reversible symptoms, but no motor weakness: 1. Dysarthria 2. Vertigo 3. Tinnitus 4. Hypacusia 5. Diplopia 6. Visual symptoms simultaneously in both temporal and nasal fields of both eyes 7. Ataxia 8. Decreased level of consciousness 9. Simultaneously bilateral paraesthesias C. At least one of the following: 1. At least one aura symptom develops gradually over 5 minutes and/or different aura symptoms occur in succession over 5 minutes 2. Each aura symptom lasts 5 and 60 minutes D. Headache fulfilling criteria B through D for 1.1 Migraine without aura begins during the aura or follows aura within 60 minutes E. Not attributed to another disorder Data from Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders: 2nd edition. Cephalalgia 2004;24(suppl 1):9–160.


TABLE 2-8 International Classification of Headache Disorders, 2nd Edition, 1.5.1 Chronic Migraine A. Headache fulfilling criteria C and D for 1.1 Migraine without aura on 15 days/ month for >3 months B. Not attributed to another disorder Data from Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders: 2nd edition. Cephalalgia 2004;24(suppl 1):9–160.

medication overuse headache pending resolution of the headache after discontinuation of analgesic medication. (Interestingly, in one study of 50 consecutive chronic daily headaches seen

in a tertiary headache clinic, all those felt to represent transformed migraine could actually be made to fit the chronic migraine category of ICHD-II if histories were taken very carefully [Levin et al, 2005]). The American Headache Society proposed a revised category of chronic migraine in an attempt to include these patients, with the softened requirement of only the majority of headaches meeting strict migraine criteria or responding to migraine-specific medication. The IHS Classification Committee agreed to include this set of criteria as an appendix diagnosis (Headache Classification Committee et al, 2006) (Table 2-10). Status migrainosus, 1.5.2, which refers to the uncommon condition of persistent migraine without abatement for 72 hours, also requires that migraine criteria be met. Here the requirement

Case 2-2 Chronic Daily Headache A 32-year-old woman with a 20-year history of severe throbbing headaches associated with nausea, photophobia, phonophobia, and exercise intolerance is referred to a tertiary headache treatment clinic because of increasing frequency of headaches to a near-daily occurrence. Many of her headaches are now nonnauseating, and phonophobia is less common. She notes that stress seems to intensify the headache, but she has identified no other triggers. Headaches have led her to take several over-the-counter medications (‘‘sometimes every day’’), which fortunately are allowing her to continue to function at her job as a receptionist. She states that she sometimes uses no medication because she gets ‘‘sick of it’’ for several weeks on end. She is on no other medication other than an oral contraceptive and has no other medical illnesses of which she is aware. Examination is unremarkable. Comment. The apparently frequent use of over-the-counter medications is very suggestive of medication overuse headache, but the persistence of headache when she abstains is problematic. The headache morphology is more typical of tension headache, but the history of migraine (as well as family history) suggests an underlying migraine pathophysiology. This patient’s most appropriate ICHD-II diagnoses would be (1) probable medication overuse headache, 8.2; (2) probable chronic tension type headache, 2.3; and (3) a history of migraine headache without aura, 1.1. It may be difficult to ascertain whether the headaches have improved sufficiently after analgesics are removed to permit a diagnosis of chronic tension-type headache. Furthermore, the migraine history and features are so suggestive here that use of proposed new criteria for chronic migraine (Table 2-10) is a compelling alternative.


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TABLE 2-9

"

Silberstein-Lipton Chronic Daily Headache Classification

Transformed Migraine With medication overuse Without overuse

"

Chronic Tension-type Headache With overuse Without overuse

"

New Daily Persistent Headache With overuse Without overuse

"

children), 1.3.2; and benign paroxysmal vertigo, 1.3.3 (Case 2-3). Finally, the worrisome migraineinduced stroke, migrainous infarction, 1.5.4, is included in the complications of migraine portion of the chapter. This diagnosis now requires both the persistence of aura symptoms for more than 60 minutes and MRI changes consistent with stroke in the appropriate brain region. TENSION-TYPE HEADACHE Not only is the pathophysiology of tensiontype headache not well understood, but even the epidemiology is somewhat unclear. In most studies tensiontype headache is much more prevalent that migraine, with an apparent

Hemicrania Continua With overuse Without overuse

From Silberstein SD, Lipton RB, Goadsby PJ. Headache in clinical practice. 2nd ed. London: Martin Dunitz, 2002. Reproduced by permission of Routledge/Taylor & Francis Group, LCC.

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seems sensible, but the longer the migraine persists unabated, the more likely migrainous features will fade with primarily pain remaining, so here too there may be unnecessary stringency in applying migraine criteria. Pure menstrual migraine and menstrually related migraine are in the appendix (A1.1.1, A1.1.2). Some have recommended inclusion of these subtypes of triggered migraine in the migraine chapter proper. Three childhood ‘‘migraine’’ syndromes exist in the ICHD-II migraine chapter, ostensibly because they are felt to be precursors of migraine. These include cyclical vomiting (spells of nausea and vomiting up to 5 days in duration), 1.3.1; abdominal migraine (recurrent abdominal pain with varying degrees of nausea in school age

Proposed International Headache Society Appendix Criteria for a Revised Chronic Migraine Category

TABLE 2-10

A. Headache on 15 or more days each month B. Diagnosis of migraine without aura 1.1 C. Eight or more headaches per month meeting criteria for 1.1 migraine without aura or 1.2 migraine with aura, or responsive to migraine-specific medication before complete migraine symptomatology develops D. No medication overuse headache, no chronic tension-type headache, no cluster headache, no new daily persistent headache E. No underlying pathology Headache Classification Committee, Olesen J, Bousser MG, Diener HC, et al. New appendix criteria open for a broader concept of chronic migraine. Cephalalgia 2006;26:742–746. Copyright # 2006. Reprinted with permission from Blackwell Publishing.


KEY POINTS:

A

Case 2-3 Childhood Pain A 12-year-old boy has a 5-year history of recurrent bouts of abdominal pain and nausea. He has also had consistent motion sickness. He recently began having unilateral temporal headaches with nausea, blurred vision, and photophobia, responsive to oral triptan medication. Extensive diagnostic evaluation has been negative, including MRI of the head and electroencephalogram. Comment. This patient seems to fit the 1.3 childhood periodic syndromes that are commonly precursors of migraine category, in particular, abdominal migraine, 1.3.2. Interestingly, he is also beginning to develop migraine. Key points here, however, are to avoid the trap of assuming the gastrointestinal symptoms are benign and to maintain vigilance in the event that new data surface to suggest possible systemic illness.

lifetime prevalence approaching 80%. Thus, tension-type headache is an important pressing public health problem. Despite this, a paucity of research on tension-type headache has been done, which probably derives in large part from the underrepresentation of tension-type headache in specialty and academic settings. The ICHD criteria for tension-type headache are notable for their vagueness and requirements for nonexistence of certain features (Table 2-11). ICHD divides tensiontype headache into three broad categories based on frequency: 2.1 Infrequent episodic tension-type headache—headache episodes on less than 1 day per month on average 2.2 Frequent episodic tension-type headache—headache episodes on 1 to 14 days per month on average 2.3 Chronic tension-type headache—headache episodes on 15 or more days per month on average Because of their arbitrariness these frequency-based categories have been controversial. Chronic tension-type headache classification, like chronic migraine, requires that tension-type headache occurs on 15 days per month or more

(Table 2-12). The prevalence of this diagnosis is really unknown, but it is likely that when patients with chronic daily headache who meet revised chronic migraine criteria are excluded (as well as those with medication overuse), the occurrence of chronic tensiontype headache is uncommon. Also controversial are the subcategories of each of the three tensiontype headache types: tension-type headache with pericranial muscle contraction and tension-type headache without pericranial muscle contraction. No consistent evidence (despite concerted efforts) documents that tension-type headache is more prone to muscle contraction than any other headache type, so the presence or absence of it may not be meaningful (Jensen, 1999; Sandrini et al, 1994).

A

The ICHD criteria for tension-type headache are notable for their vagueness and requirements for nonexistence of certain features. The term trigeminal autonomic cephalalgia was coined to include three headache types that are felt to be somehow related: cluster headache, paroxysmal hemicrania, and SUNCT.

CLUSTER HEADACHE AND TRIGEMINAL AUTONOMIC CEPHALALGIA The term trigeminal autonomic cephalalgia was coined to include three headache types that are felt to be somehow related: cluster headache, paroxysmal hemicrania, and SUNCT. All have headache brevity in common


43


TABLE 2-11 International Classification of Headache Disorders, 2nd Edition, 2.1 Infrequent Episodic Tension-type Headache A. At least 10 episodes occurring on Alpha2 >Beta. y DA2 >DA1. Mathew NT. The abortive treatment of migraine. In: Gallagher RM, ed. Drug therapy for headache. New York: Marcel Dekker, 1991:95–114. Reprinted with permission from Taylor and Francis.


TABLE 5-8

Dihydroergotamine Mesylate Versus Ergotamine Tartrate: Clinical Comparisons

Safety/Efficacy Measure

Dihydroergotamine Mesylate

Ergotamine Tartrate

5-hydroxytryptamine 1 (5-HT1) activity

++

++

Arterial vasoconstriction

+

+++

Venoconstriction

++

++

-Adrenergic antagonist activity

++

+

Nausea/vomiting

+

+++

Uterotonic effects

+

++

Pain relief

+++

+++

Headache recurrence

+

++

Rebound headache

0

++

0 indicates none; + mild; ++ moderate; +++ prominent. Adapted from Lipton RB. Ergotamine tartrate and dihydroergotamine mesylate: safety profiles. Headache 1997;37:S33–S41. Copyright # 1997. Reprinted with permission from Blackwell Publishing.

mucosa and a high first-pass metabolism, in contrast to the absolute bioavailability of intramuscular (IM) DHE (100%) (Little et al, 1982). The absolute bioavailability of DHE following intranasal (IN) administration is approximately 40% (Bigal and Tepper, 2003). Peak plasma levels occur approximately 1 to 2 minutes after intravenous (IV) administration, 24 minutes after IM administration, and 30 to 60 minutes after IN administration. IN administration of DHE avoids firstpass hepatic metabolism (Ziegler et al, 1994). Both IN and parenteral administration of DHE are reasonable. Studies published in the 1990s have shown comparable efficacy between SC and IM administrations (Winner et al, 1993). Anecdotally, clinicians advise patients to mix DHE with 0.25 mL to 0.50 mL of 1% to 2% lidocaine in the same syringe (they are miscible) to reduce injection-site burning. The patient will need training to selfadminister DHE by IM or SC injection, starting with a single injection of

DHE 1 mg, which may be repeated, if needed, after 60 minutes. Once again, titration to a subnauseating dose is important. Maximum dosing is 3 mg/d, 21 mg per week. Dosing of IN DHE is one spray (0.5 mg) into each nostril (without sniffing) at the first sign of migraine, followed 15 minutes later by an additional spray into each nostril. Thus, the total dose administered is 2 mg in four sprays. The maximum recommended dose is 4 mg per attack (Raskin, 1988). The utility of DHE nasal spray is limited clinically by relatively low efficacy and high frequency of prolonged nasal stuffiness. The advantage of ergots is that once headache relief is established, recurrence of migraine is low. In randomized clinical trials, oral ET was found superior to placebo but inferior to oral sumatriptan 100 mg (Tfelt-Hansen, 2001; Tfelt-Hansen et al, 2000). IN DHE was found superior to placebo but less effective than SC and IN sumatriptan, at least for initial response. Recurrence was lower


99

" ACUTE TREATMENT OF MIGRAINE

Case 5-5 Patient E wakes up with a vomiting migraine, takes a 100-mg sumatriptan tablet, and only partially holds it down. She calls and says she needs a rescue medication. What options does she have to avoid a trip to the emergency department? Comment. The easiest rescue would be sumatriptan SC, since forms of sumatriptan can be mixed. This can be supplemented with a neuroleptic suppository, since she is vomiting. If she comes to the office, parenteral ketorolac, steroids, or valproate can also be used.

with IN DHE than with sumatriptan (Winner et al, 1996). In summary, the issues for use of ergots are as follows: (1) They cannot TABLE 5-9

be mixed with each other or triptans. (2) They are difficult to use, requiring titration of dose. (3) ET is highly associated with medication overuse

Parenteral Acute Treatments for Migraine for Use in Clinic or Emergency Department

Medication

Dose

Route

Other Facts

Dihydroergotamine 1-mg or maximum SC, IM, IV May be mixed with subnauseating dose lidocaine in SC or IM dosing; recurrence is low; nonsedating; contraindicated with vascular disease

100

Sumatriptan

6 mg

SC

Nonsedating; contraindicated with vascular disease

Metoclopramide

10 mg

IV

Risk of extrapyramidal effects and mild sedation

Promethazine

25 mg to 50 mg

IM, IV

Risk of extrapyramidal effects and sedation

Prochlorperazine

10 mg

IV

Risk of extrapyramidal effects and sedation

Droperidol

2.5 mg to 5.0 mg

IV

Risk of QT prolongation, extrapyramidal effects and sedation

Ondansetron

4 mg to 8 mg

IV

Nonsedating antinauseant

Ketorolac

30-mg IV, 60-mg IM IM, IV

Nonsedating

Dexamethasone

4 mg to 10 mg

Nonsedating

Valproate

500 mg to 1000 mg IV

Nonsedating

Magnesium

1g

Nonsedating; works best for patients with migraine with aura

IM, IV

IV

SC = subcutaneous; IM = intramuscular; IV = intravenous.


headache (Saper, 1987). (4) Adverse events can be significant. (5) They are not clearly superior to the more convenient triptans, except with respect to IV DHE. Both triptans and ergots are contraindicated in the setting of vascular disease, and when vascular risk factors are present, a functional workup should be undertaken prior to administering the first dose in the office. As noted, both triptans and ergots are vasoconstrictive. Also, both triptans and ergots are contraindicated in hemiplegic and basilar-type migraine within 24 hours of each other. RESCUE AND EMERGENCY TREATMENT As noted above in the section on opioids, the use of narcotics as rescue treatment for status migrainosus should be avoided. In an outpatient setting, when a migraine appears to spiral out of control due to late or inadequate treatment, this author rec-

ommends use of SC sumatriptan, repetitive DHE nasal spray, or a brief several-day course of steroids, such as dexamethasone (Case 5-5). In the clinic or emergency department, a variety of IM or IV treatments can be used together or separately, with the only contraindication that of mixing triptans and ergots in the same day, and that of avoiding triptans and ergots in patients with vascular disease. Rescue treatments are listed with doses in Table 5-9. CONCLUSIONS Acute treatment of migraine involves stratified care and preferential use of migraine-specific medications for those with disabling migraines. Nonspecific treatment is probably less effective for severe migraine, and ergots are more difficult to use. Rescue can involve medications from multiple classes, including triptans or ergots, neuroleptics, steroids, nonsteroidal anti-inflammatories, valproate, and magnesium.

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Carasso RL, Yehuda S. The prevention and treatment of migraine with an analgesic combination. Br J Clin Pract 1984;38:25–27.

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Dahlof C, Bjorkman R. Diclofenac-K (50 and 100 mg) and placebo in the acute treatment of migraine. Cephalalgia 1993;13:117–123. A typical well-controlled nonsteroidal anti-inflammatory drug (NSAID) trial for acute treatment.

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Diener HC, Pffafenrath V, Pageler L, et al. The fixed combination of acetylsalicylic acid, paracetamol and caffeine is more effective than single substances and dual combination for the treatment of headache: a multicentre, randomized, double-blind, single-dose, placebo-controlled parallel group study. Cephalalgia 2005;25:776–787. A superb factorial study in which the components of aspirin/amphetamine/caffeine (AAC) are compared with the combination and placebo.

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Dowson AJ, Tepper SJ, Baos V, et al. Identifying patients who require a change in their current acute migraine treatment: the Migraine Assessment of Current Therapy (Migraine-ACT) questionnaire. Curr Med Res Opin 2004;20:1125–1135. The validation study on Migraine Assessment of Current Therapy (Migraine-ACT).

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Gawel MJ, Szalai JF, Stiglick A, et al. Evaluation of analgesic agents in recurring headache compared with other clinical pain models. Clin Pharmacol Ther 1990;47:504–508. A thoughtful guide to analgesic treatment in headache.

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Iversen HK, Nielsen TH, Olesen J, Tfelt-Hansen P. Arterial responses during migraine headaches. Lancet 1990;336:837–839.

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102

Winner of the Wolff award for best headache research of 2005, this is a must-read study describing the effects of NSAIDs on central sensitization and of the deleterious effects of opioids in treating acute migraine.

"

Kellstein DE, Lipton RB, Geetha R, et al. Evaluation of a novel solubilized formulation of ibuprofen in the treatment of migraine headache: a randomized, double-blind, placebo-controlled, dose-ranging study. Cephalalgia 2000;20:233–243. The regulatory trial for the indication of ibuprofen in the acute treatment of migraine.


"

Kimball RW, Friedman AP, Vallejo E. Effect of serotonin in migraine patients. Neurology 1960;10:107–111. Early description of serotonin effects.

"

Limmroth V, Przywara S. Analgesics. In: Diener HC, ed. Drug treatment of migraine and other headaches. New York: Karger, 2000:30–43.

"

Lipton RB. Ergotamine tartrate and dihydroergotamine mesylate: safety profiles. Headache 1997;37:S33–S41.

"

Lipton RB, Goadsby PJ, Sawyer JPC, et al. Migraine: diagnosis and assessment of disability. Rev Contemp Pharmacother 2000a;11:63–73. Introduction of the Migraine Disability Assessment Scale (MIDAS).

"

Lipton RB, Stewart WF. Acute migraine therapy: do doctors understand what patients with migraine want from therapy? Headache 1999;39:S20–S26. Establishes sustained pain free as the appropriate clinical goal in acute treatment.

"

Lipton RB, Stewart WF, Ryan RE Jr, et al. Efficacy and safety of acetaminophen, aspirin and caffeine in alleviating migraine headache pain: three double-blind, randomized, placebo-controlled trials. Arch Neurol 1998;55:210–217. Regulatory trial for the indication of AAC in the acute treatment of migraine.

"

Lipton RB, Stewart WF, Stone AM, et al. Stratified care vs. step care strategies for migraine. The Disability in Strategies of Care (DISC) Study: a randomized trial. JAMA 2000b;284:2599–2605. A must-read study of the requirement for disability assessment in the decision on acute migraine treatment.

"

Little PJ, Jennings GL, Skews H, Bobik A. Bioavailability of dihydroergotamine in man. Br J Clin Pharmacol 1982;13:785–790.

"

Massiou H, Serrurier D, Lasserre O, Bousser MG. Effectiveness of oral diclofenac in the acute treatment of common migraine attacks; a double-blind study versus placebo. Cephalalgia 1991;11:59–63.

"

Mathew NT. Dosing and administration of ergotamine tartrate and dihydroergotamine. Headache 1997;37:S26–S32.

"

Mathew NT. The abortive treatment of migraine. In: Gallagher RM, ed. Drug therapy for headache. New York: Marcel Dekker, 1991:95–114.

"

Mu¨Iler-Schweinitzer E. Pharmacological actions of the main metabolites of dihydroergotamine. Eur J Clin Pharmacol 1984;26:699–705.

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Mu¨ller-Schweinitzer E, Weidmann H. Basic pharmacological properties. In: Berde B, Schild HO, eds. Ergot alkaloids and related compounds. Berlin: Springer-Verlag, 1978:87–232.

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Rapoport A, Lipton R, Williams P, Sawyer J. Cost-effectiveness of stratified care in the management of migraine. Value Health 2000a;3:80. Post-hoc pharmacoeconomic analysis of the Disability in Strategies of Care (DISC) study.


103


"

Rapoport A, Williams P, Sawyer J. Stratified care: cost-efficient in the management of migraine. Headache 2000b;40:426. Post-hoc pharmacoeconomic analysis of the DISC study.

"

Rapoport AM, Tepper SJ, Bigal ME, Sheftell FD. The triptan formulations: how to match patients and products. CNS Drugs 2003;17:431–447.

"

Raskin NH. Headache. 2nd ed. New York: Churchill Livingstone, 1988.

"

Saper JR. Ergotamine dependency–a review. Headache 1987;27:435–438. Classic review.

"

Sculpher M, Millson D, Meddis D, Poole L. Cost-effectiveness analysis of stratified versus stepped care strategies for acute treatment of migraine: the Disability in Strategies for Care (DISC) Study. Pharmacoeconomics 2002;20:91–100. The largest and best post-hoc pharmacoeconomic analysis of the DISC study.

"

Sheftell FD, Dahlof CG, Brandes JL, et al. Two replicate randomized, double-blind, placebo-controlled trials of the time to onset of pain relief in the acute treatment of migraine with a fast-disintegrating/rapid-release formulation of sumatriptan tablets. Clin Ther 2005;27:407–417. Onset study for the RT sumatriptan tablets.

"

Sheftell FD, Weeks RE, Rapoport AM, et al. Subcutaneous sumatriptan in a clinical setting: the first 100 consecutive patients with acute migraine in a tertiary care center. Headache 1994;34:67–72. First study to note decreased effectiveness of sumatriptan late in attacks.

"

Silberstein SD. Practice parameter: evidence-based guidelines for migraine headache (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2000;55:754–762. The American Academy of Neurology (AAN)/American Headache Society/ US Headache Consortium Guidelines with links to federally funded technical reports on prophylaxis, acute treatment, imaging, and nonpharmacological treatments.

"

Silberstein SD. The pharmacology of ergotamine and dihydroergotamine. Headache 1997;37:S15–S25.

"

Silberstein SD, McCrory DC. Opioids. In: Diener HC, ed. Drug treatment of migraine and other headaches. New York: Karger, 2000:222–236.

"

Silberstein SD, Young WB. Safety and efficacy of ergotamine tartrate and dihydroergotamine in the treatment of migraine and status migrainosus. Working Panel of the Headache and Facial Pain Section of the American Academy of Neurology. Neurology 1995;45:577–584.

104

A must-read, the professional guideline recommendations on ergots of the AAN.

"

Snow V, Weiss K, Wall EM, et al. Pharmacologic management of acute attacks of migraine and prevention of migraine headache. Ann Intern Med 2002;137:840–849. More of the US Headache Consortium Guidelines, this time published in the internal medicine literature.


"

Stewart WF, Lipton RB, Whyte MS, et al. An international study to assess reliability of the Migraine Disability Assessment (MIDAS) score. Neurology 1999;53:988–994.

"

Tepper SJ, Baos V, Dowson AJ, et al. The Migraine Assessment of Current Therapy (Migraine-ACT) Questionnaire: further investigation of study methodology and results. Headache Care 2005;2:27–32.

"

Tepper SJ, Meddis D. Reducing the cost of impairment of normal activities due to migraine: a stratified care approach. Headache 2000;40:434.

"

Tepper SJ, Rapoport AM. The triptans: a summary. CNS Drugs 1999;12:403–417.

"

Tfelt-Hansen P. Ergotamine, dihydroergotamine: current uses and problems. Curr Med Res Opin 2001;17:S30–S34. A review with the personal point of view of the author about the current uses and problems of ergotamine and dihydroergotamine.

"

Tfelt-Hansen P, Olesen J. Paracetamol (acetaminophen) versus acetylsalicylic acid in migraine. Eur Neurol 1980;19:163–165.

"

Tfelt-Hansen P, Saxena PR, Dahlof C, et al. Ergotamine in the acute treatment of migraine: a review and European consensus. Brain 2000;123:9–18. Presents the European consensus regarding the treatment of migraine with ergotamine.

"

Uzogara E, Sheehan DV, Manschreck TC, Jones KJ. A combination drug treatment for acute common migraine. Headache 1986;26:231–236.

"

Ware JE, Bayliss MS, Dahloff C, et al. Developing short static assessments from the Headache Impact Test (HIT) item pool. Cephalalgia 2000;20:308. Provides the Headache Impact Test, another validated disability assessment tool.

"

Winner P, Dalessio D, Mathew N, et al. Office-based treatment of acute migraine with dihydroergotamine mesylate. Headache 1993;33:471–475. Study on outpatient use of dihydroergotamine.

"

"

Winner P, Ricalde O, Le Force B, et al. A double-blind study of subcutaneous dihydroergotamine vs subcutaneous sumatriptan in the treatment of acute migraine. Arch Neurol 1996;53:180–184. Wolff HG. Headache and other head pain. New York: Oxford University Press, 1963. The classic text.

"

Ziegler D, Ford R, Kriegler J, et al. Dihydroergotamine nasal spray for the acute treatment of migraine. Neurology 1994;44:447–453. Regulatory trial for indication of nasal dihydroergotamine for acute migraine treatment.


105

CHRONIC DAILY HEADACHE AND ITS SUBTYPES Marcelo E. Bigal, Fred D. Sheftell

ABSTRACT Chronic daily headache is one of the more frequently seen headache syndromes at major tertiary care centers worldwide as well as in office practices of general neurologists. One of the major classification approaches subdivides chronic daily headache into four headache types: transformed or chronic migraine, chronic tension-type headache, new daily persistent headache, and hemicrania continua. In this chapter the authors review the clinical features and classification of the chronic daily headaches, as well as the pathophysiology of chronic daily headache with a focus on chronic migraine. Effective treatment regimens will be discussed, which include the following steps: (1) education and support to the patient, establishing expectations and a follow-up plan; (2) use of nonpharmacological and behavioral therapies; (3) discontinuation of overused and potentially offending medications plus caffeine by outpatient or inpatient detoxification procedures; and (4) institution of a program of acute care and preventive pharmacological therapy.

INTRODUCTION Chronic daily headache is a clinical syndrome defined by primary headaches that occur for 4 or more hours a day on 15 or more days a month over more than 3 months (Mathew et al, 1987; Saper, 1982; Silberstein, 1993). Chronic daily headache is one of the more common presentations to headache specialty care centers and afflicts 4% to 5% of the general population (Castillo et al, 1999; Scher et al, 1998). Most patients with chronic daily headache report frequent and severe impairment of their role functioning and well-being (Spierings et al, 2000), highlighting the important impact of this group of headaches on quality of life. The burden of chronic daily headache is severe. Studies show that subjects with chronic daily headache have significantly lower health-related quality of life scores when compared with pa-

KEY POINT:

A

Chronic daily headache is a clinical syndrome defined by primary headaches that occur for 4 or more hours a day on 15 or more days a month over more than 3 months.

tients with episodic headaches (Bigal et al, 2003). As a syndrome, chronic daily headache has been included in neither the first nor the second edition of the International Classification of Headache Disorders (ICHD-I and ICHD-II) (Headache Classification Subcommittee of the International Headache Society, 1988; Headache Classification Subcommittee of the International Headache Society, 2004). As a consequence, several separate proposals for their classification have emerged. The Silberstein and Lipton criteria have been most widely used (Silberstein et al, 1996). The Silberstein and Lipton criteria divided primary chronic daily headache into transformed migraine, chronic tension-type headache, new daily persistent headache, and hemicrania continua, and subclassified each of these into subtypes ‘‘with medication


133

" CHRONIC DAILY HEADACHE AND SUBTYPES

KEY POINTS:

A

A

Chronic daily headache is usually subdivided into chronic or transformed migraine, chronic tension-type headache, new daily persistent headache, and hemicrania continua. The prevalence of chronic daily headache in the population ranges from 2.4% to 4.7%.

overuse’’ or ‘‘without medication overuse’’ (Table 7-1). Of these, the ICHD-I (Headache Classification Committee of the International Headache Society, 1988) classification included only chronic tension-type headache, while the ICHD-II (Headache Classification Subcommittee of the International Headache Society, 2004) has detailed diagnostic criteria for all four types of primary chronic daily headache of long duration. Evidence, however, suggested that the ICHD-II scheme remained cumbersome and not intuitive in the classification of adults with chronic daily headache (Bigal et al, 2004a; Silberstein et al, 1996). As a consequence, revised criteria for chronic migraine was proposed (Bigal et al, 2006). Recently, a revised version of the criteria for chronic migraine, endorsed by the ICHD-II (Headache Classification Committee of

TABLE 7-1

Silberstein-Lipton Criteria for Classification of Chronic Daily Headache

Daily or Near-daily Headache Lasting > 4 Hours for >15 Days Per Month 1.8 Transformed Migraine

134

1.8.1 With overuse 1.8.2 Without overuse 2.2 Chronic Tension-type Headache 2.2.1 With overuse 2.2.2 Without overuse 4.7 New Daily Persistent Headache 4.7.1 With overuse 4.7.2 Without overuse 4.8 Hemicrania Continua 4.8.1 With overuse 4.8.2 Without overuse

the International Headache Society, 2006), has been published as well and will be discussed herein. Since transformed migraine, as defined by Silberstein and Lipton, and chronic migraine, as defined by the ICHD-II, refer to analogous disorders representing the result of episodic migraine that progressed over time, and since accepted criteria for chronic migraine were just recently published, both definitions will be addressed in this chapter. Clinical features of the other chronic daily headaches will be discussed as well as strategies for the treatment of chronic daily headache. Potential prospects for avoiding the development of chronic daily headache will be emphasized. Since medication overuse is a strong risk factor for the development of chronic daily headache, this chapter is complemented by the chapter Medication Overuse Headache. EPIDEMIOLOGY OF CHRONIC DAILY HEADACHES The prevalence of chronic daily headache is remarkably consistent among studies, ranging from 2.4% (Hagen et al, 2000) to 4.7% (Castillo et al, 1999). In the United States, the prevalence is 4.1%. In the population, transformed migraine and chronic tension-type headache are equally prevalent (both around 2%) (Scher et al, 1998). The prevalence of new daily persistent headache and hemicrania continua is unknown. Clinic-based studies show that chronic daily headache accounts for about 10% to 20% of the patients in European headache clinics although, according to Dowson and colleagues (2005), this is likely an underestimation. In the United States, studies show that from 50% to 80% of all patients presenting to a headache clinic have chronic daily headache (Bigal et al, 2004a; Mathew, 1993). In this setting, transformed migraine/chronic migraine (transformed migraine and


chronic migraine refer to the same condition; the terms will be used synonymously in this chapter) is by far the most common type of chronic daily headache. In a study by Mathew (1993), 77% of the patients with chronic daily headache had transformed migraine. In a large study conducted at the New England Center for Headache, transformed migraine represented 87.4% of the cases of chronic daily headache seen in a headache specialty center (Bigal et al, 2004a). The relative frequency of the different headache subtypes presenting to a headache clinic is different in adults and in adolescents. Chronic tensiontype headache and new daily persistent headache are more common in adolescents than in adults (respectively, 10.0% versus 0.9% and 20.0% versus 10.0%), transformed migraine is more common in adults, and hemicrania continua is equally rare (Bigal et al, 2005a). Furthermore, the clinical presentation, as discussed below, of transformed migraine is different in adolescents than in adults. Adolescents with transformed migraine have a higher frequency of migraine attacks than adults (Bigal et al, 2005b). CLINICAL CHARACTERIZATION OF CHRONIC DAILY HEADACHES Transformed Migraine/ Chronic Migraine Patients with transformed migraine/ chronic migraine typically have a history of migraine. It is more frequent in women with a history of migraine without aura. Subjects usually report a process of transformation over months or years, and as headache increases in frequency, associated symptoms become less severe and frequent. The process of transformation frequently ends in a pattern of daily or nearly daily headache that resembles chronic tension-type headache, with some attacks of full-migraine superimposed

(Mathew et al, 1987; Rapoport et al, 1996; Saper, 1982; Scher et al, 1998; Silberstein, 1993). In the clinical setting, migraine transformation most often is related to acute medication overuse, but transformation may occur without overuse. In the more general population, most cases of transformed migraine are not related to medication overuse (Scher et al, 1998). Multiple risk factors may be involved in these cases (see section on risk factors for the development of chronic daily headache). The Silberstein and Lipton criteria basically define transformed migraine as those cases that satisfy two situations (Table 7-2) as follows: (1) The headache is not a chronic daily headache and develops de novo in a previously headache-free subject (if a chronic daily headache develops de novo, the diagnosis is new daily persistent headache). (2) The headache has one of the three following links with migraine: (A) a history of International Headache Society–defined migraine; (B) a period of escalating headache frequency; and (C) concurrent superimposed attacks of migraine that fulfill the International Headache Society criteria. Recent proposed modifications for these criteria, which will most likely be endorsed by the International Headache Society, are listed in Table 7-2. The ICHD-II included criteria for chronic migraine that required 15 or more days of migraine per month (Headache Classification Subcommittee of the International Headache Society, 2004), but these criteria were restrictive in clinical practice and research (Bigal et al, 2006; Bigal et al, 2004a). As a consequence of the many research studies showing that ICHD-II criteria for chronic migraine were cumbersome, the International Headache Society has recently revised the criteria for chronic migraine. The new criteria will be moved to the appendix, awaiting evidence to support their

KEY POINTS:

A

A

A

A

A

In the United States, the prevalence of chronic daily headache is 4.1%. In the population, chronic or transformed migraine and chronic tension-type headache are equally prevalent; new daily persistent headache and hemicrania continua are rare. In specialty care, chronic/ transformed migraine is by far the most common chronic daily headache subtype. Chronic/ transformed migraine is a chronic daily headache that does not develop abruptly. Subjects with chronic/ transformed migraine usually report a process of transformation over months or years.


135


KEY POINT:

A

As headache increases in frequency, associated symptoms become less severe and frequent.

TABLE 7-2

International Classification of Headache Disorders (2006) Revised and Silberstein-Lipton Diagnostic Criteria for Primary Chronic Daily Headache

Silberstein-Lipton From 1996 Transformed Migraine

ICHD-II Revised Chronic Migraine

Daily or almost daily (>15 days per month) head pain for >1 month

Diagnostic criteria: Headache on 15 days per month for >3 months

Average headache duration of > 4 hours per day (if untreated) At least one of the following: (1) History of episodic migraine meeting any IHS criteria 1.1 to 1.6 (2) History of increasing headache frequency with decreasing severity of migrainous features over at least 3 months (3) Headache at some time meets IHS criteria for migraine 1.1 to 1.6 other than duration

Does not meet criteria for new daily persistent headache (4.7) or hemicrania continua (4.8)

Occurring in a patient with at least five prior migraine attacks On 8 days per month, for at least 3 months, headache fills criteria for migraine (C1 and/or C2) (1) Unilateral Throbbing Moderate or severe Aggravated by physical activity Nausea and/or vomiting Photophobia and phonophobia (2) Treated or relieved with triptans or ergotamine compounds No medication overuse and not attributable to other causative disorder

IHS = International Headache Society.

136

utility (Table 7-2). Basically, chronic migraine is classified as 15 days or more of headache per month and 8 or more days of migraine or use of acute migraine medications. If patients are overusing acute medication, they should be classified as having medication overuse headache (Case 7-1). Phenotype of chronic/transformed migraine. Differences exist regarding the clinical presentation of transformed migraine in adolescents and adults. Most adults with transformed migraine have fewer than 15 days of full-blown migraine per month and more days of headache resembling tension-type headache than of migraine. In contrast, transformed migraine in adolescents is replete with

migraine attacks. Also, most adults with transformed migraine overuse acute medication (84.0%), while most adolescents (58.9%) do not (Bigal et al, 2004b). Phenotype of chronic/transformed migraine changes over time. In a recent study of 402 subjects with transformed migraine, the proportion of migraine attacks decreased with age (with a proportional increase of tension-type headache attacks), from 71% below the age of 30 years to 22% at age 60 or above. It was higher in those with shorter interval from the onset of migraine to the onset of chronic daily headache (less than 5 years, P=.003), and in those with a more recent onset of chronic daily headache (less than


KEY POINTS:

A

Case 7-1 A 42-year-old woman started to have attacks of headache when she was in her teens. At that time, attacks were related to menstruation and were bilateral, severe, and throbbing. Nausea, as well as photophobia, was always present. Phonophobia was sometimes also present. She remembers that, when she was 20, she started to have attacks unrelated to menstruation as well. She used no medication to prevent her headaches and used ibuprofen as her acute therapy. When she was in her 30s, she realized that her headaches were becoming more frequent. At that time, the headaches were moderate or severe most of the days, and she started to use ibuprofen almost daily. Her primary care doctor prescribed propranolol at a dose of 40 mg 2 times a day to prevent her headaches. Since then she has also used amitriptyline and verapamil, with no success. She now has headache every day. About 5 times per month (and always during her menstrual cycle) the headaches are severe and associated with nausea, photophobia, and phonophobia. On most of the other days the headache is mild and without associated symptoms. She uses ibuprofen only to treat the severe headaches. She is married, obese (body mass index of 32), and without symptoms of depression. She has also been investigated for arthritis. Because of her obesity, verapamil was switched to topiramate 100 mg/d. With this treatment she remitted to episodic migraine and now has eight headache days per month. Comment. This case illustrates the process of transformation from episodic to chronic migraine and, as discussed in the text, includes some points that deserve to be emphasized: (1) The phenotype of migraine/ chronic migraine changes over time. Just after transformation, most attacks resemble migraine. As time evolves, the attacks become less typical and resemble tension-type headache. (2) Of the risk factors for transformation, this patient is obese and has arthritis.

6 years, P3 months C. At least two of the following pain characteristics: 1. Bilateral location 2. Pressing/tightening (nonpulsating) quality 3. Mild or moderate intensity 4. Not aggravated by routine physical activity such as walking or climbing D. Both of the following: 1. No more than one of photophobia, phonophobia, or mild nausea 2. Neither moderate or severe nausea nor vomiting E. Not attributed to another disorder

relatively abrupt onset of an unremitting primary chronic daily headache; ie, a patient without a previous headache syndrome develops a chronic daily headache that does not remit. The patient’s remembering the circumstances, place, and date that the headache began is a pathognomonic feature. It is the new onset of this primary daily headache that is the most important feature (Rozen, 2003). The clinical features of the pain are not considered in making the diagnosis, which simply requires absence of history of evolution from migraine or episodic tension-type headache (Table 7-4) (Silberstein et al, 1996). The ICHD-II addresses new daily persistent headache as a single diagnosis in those with a new-onset chronic daily headache that resembles chronic tension-type headache. A new-onset chronic daily headache with migrainous features cannot be classified as new daily persistent headache according to the ICHD-II criteria, whereas the Silberstein and Lipton classification allows this diagnosis in patients with headache features of migraine or epi-

sodic tension-type headache if the disorder arises abruptly (Case 7-3). Hemicrania Continua Hemicrania continua is an uncommon primary headache disorder first described as a syndrome by Sjaastad and Spierings (1984). This daily and continuous strictly unilateral headache is defined by its absolute response to therapeutic doses of indomethacin. Pain is moderate with exacerbations of increased severity, and autonomic symptoms accompany these exacerbations although less prominently than in cluster headache and chronic paroxysmal hemicrania. Some bilateral or alternating side cases have been reported (Case 7-4). PATHOPHYSIOLOGY OF CHRONIC DAILY HEADACHES Although the source of pain in primary chronic daily headache is unknown and may be dependent on the subtype, recent studies suggest that the following mechanisms, alone or in


KEY POINT:

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Case 7-3 A 19-year-old college student presents to a headache clinic stating that exactly 6 months ago he started to have daily headaches. The onset was abrupt. He only had occasional headaches before this. He can precisely remember the day of onset. At that time he reports that he was under a great deal of stress because of examinations. He denies head trauma, fever, and systemic symptoms currently and at onset. He is a poor historian and provides no other relevant information. Because he had a new-onset headache, his neurologist ordered extensive investigation, including brain neuroimaging (magnetic resonance imaging), chest computed tomographic scan, serological tests, screenings for infectious diseases, including Lyme disease, and thyroid hormones. Since he is overweight, a spinal tap was performed as well. All tests were normal. The headache calendar shows that in the past month the patient has had 15 headaches that were mild and sounded like tension-type headache, 12 headaches that reached moderate severity and usually met criteria for probable migraine, and three severe migraine headaches. He has already used amitriptyline, propranolol, topiramate, and levetiracetam, all prescribed by his neurologists, with no success. He uses no acute medications. He says that nothing helps. He is frustrated and anxious. He is being treated with topiramate and propranolol but continues to have daily headaches. Comment. Primary CDHs may start de novo without evolving from episodic forms. In such cases, the diagnosis should be NDPH. Although the ICDH-II states that NDPH attacks resemble tension-type headaches most of the time, not infrequently patients with NDPH will report plenty of migraine symptoms. NDPH is often a refractory headache subtype.

combination, contribute to the process (Welch and Goadsby, 2002): (1) abnormal excitation of peripheral nociceptive afferent fibers in the meninges; (2) enhanced responsiveness of trigeminal nucleus caudalis neurons; (3) decreased pain modulation from higher centers, such as the periaqueductal gray matter; (4) spontaneous central pain generated by activation of the ‘‘on cells’’ in the medulla; (5) decreased serotonin levels; and (6) central sensitization. Since transformed migraine is the most important chronic daily headache in the clinical setting, the following discussion will review possible mechanisms involved in the transformation. Chronic Migraine as the Result of Progression of Disease Recent evidence suggests that a subgroup of migraine sufferers may have

The pathophysiology of chronic daily headache is poorly known.

a clinically progressive disorder (Scher et al, 2003). An imaging study has shown that iron deposition occurs in the periaqueductal gray area in subjects with chronic headaches (Welch et al, 2001). The periaqueductal gray area is related to a descending analgesic network and is important in controlling pain by providing endogenous analgesia. It is closely related to the trigeminal nucleus caudalis. In this study, the iron levels were increased in migraine sufferers, compared with controls, and in chronic daily headache sufferers compared with migraineurs. These findings may be directly attributable to iron-catalyzed, free-radical cell damage. Iron deposition may reflect progressive neuronal damage related to recurrent migraine attacks. It can be hypothesized that repetitive central sensitization of the trigeminal neurons


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For chronic/ transformed migraine, repetitive central sensitization of the trigeminal neurons may be associated with neuronal damage, predisposing to disease progression.

Case 7-4 A 52-year-old divorced woman presents to the clinic with a history of unilateral daily headaches for the past 4 years. Her headaches are always on the right side and are most severe around the eye. She says that most of the time the headache is mild, but once or twice a day it reaches moderate intensity and she needs to use analgesics. She says that the headache is dull, not throbbing, and sometimes is sharp and knifelike. She has been to several physicians, and she has used topiramate, gabapentin, carbamazepine, lamotrigine, and several antidepressants without improvement. When the pain is severe, she uses aspirin plus butalbital plus caffeine (Fiorinal) with no more than mild relief (she does not know if the medication helps or if the headache decreases in severity naturally). The headache is always present, and she gets relief only when she sleeps. All investigations are normal. She reports no other symptoms, including ptosis, red eye, or lacrimation. However, examination during an exacerbation reveals a red eye on the side of the pain. She responds completely and almost immediately to indomethacin, 75 mg twice daily. However, she cannot continue the medication because of gastrointestinal intolerance. Rofecoxib has provided good but not total response, but after the drug is withdrawn from the market, she resumes a lower dose of indomethacin. Comment. The fourth CDH subtype is HC. HC is a strictly unilateral CDH. Although the headache is not very severe, during exacerbations, ipsilateral autonomic symptoms may be seen. This headache is usually absolutely responsive to indomethacin, and this drug should be tried in any primary CDH that is side-locked.

correlates with iron deposition in the periaqueductal gray area, and therefore, migraine attacks predispose to disease progression. Evidence of migraine progression also comes from a recent neuroimaging study. Kruit and colleagues (2004) used a cross-sectional design to study Dutch adults aged 30 to 60 years. They showed that male subjects with migraine with aura were at an increased risk of posterior circulation infarct. Additionally, women with migraine, with or without aura, were at a higher risk of deep white matter lesions than controls. The white matter lesions increased with attack frequency, possibly demonstrating progression of the disease. Finally, in a longitudinal epidemiological study, Scher and colleagues (Scher et al, 2003; Scher et al, 2004) showed that over the course of 1 year, 3% of individuals with episodic headache (headache frequency

2 to 104 days per year) progressed to chronic daily headache. Burstein and colleagues showed that approximately 75% of migraine sufferers develop central sensitization (sensitization of the second order trigeminal neuron, which is clinically manifested by the development of cutaneous allodynia) during the course of a migraine attack (Burstein et al, 2000; Burstein and Jakubowski, 2004). Central sensitization appears to be associated with triptan refractoriness. Central sensitization explains the progression of attacks but also may play a role in the progression of the disease itself. It has been suggested that repeated central sensitization episodes are associated with permanent neuronal damage at the level of, or close to, the periaqueductal gray, with poor modulation of pain, refractoriness to preventive treatment, and disease progression.


Risk Factors for the Development of Chronic/Transformed Migraine Limited evidence exists about risk factors for migraine progression. A study found that the prevalence of chronic daily headache decreased slightly with age and was higher in women (odds ratio [OR]=1.65 [1.3–2.0]) and in divorced, separated, or widowed individuals (OR=1.50 [1.2–1.9]) (Saper et al, 1994; Saper et al, 2001). Chronic daily headache prevalence was inversely associated with educational level. Having less than a high-school education was associated with more than a threefold risk of chronic daily headache compared with those with a graduate school–level education (OR=3.56 [2.3– 5.6]). Chronic daily headache was also associated with a self-reported physician diagnosis of arthritis (OR=2.50 [1.9– 3.3]) or diabetes (OR=1.51 [1.01–2.3]), with previous head trauma, and with medication overuse (Scher et al, 2003). Importantly, the risk of new-onset chronic daily headache increased nonlinearly with baseline headache frequency; elevated risk was primarily limited to controls with more than about two headaches per month. Finally, the strongest risk factor for the development of chronic daily headache was obesity (OR=5.53, [1.4–21.8]). In most clinical studies of chronic daily headache, overuse of analgesics or other acute care medication figures prominently (Katsarava et al, 2001; Katsarava et al, 2004). This issue is discussed in detail under a separate review . in this issue of TREATMENT OF CHRONIC DAILY HEADACHE Principles of Treatment As with other lifelong illness, several fundamental management considerations are important for treatment success in patients with chronic daily headache.

Patients suffering from long-duration chronic daily headache often present not only with acute medication overuse, but also with psychiatric and somatic comorbidity, low frustration tolerance, and both physical and emotional dependence (Holroyd and Andrasik, 1982; Holroyd et al, 2001). In patients with primary chronic daily headache, it is important to identify the subtype of chronic daily headache and evaluate for the presence of analgesic overuse and comorbidities (including depression and anxiety). A combination of pharmacological, nonpharmacological, behavioral, and sometimes physical interventions is usually necessary for a favorable outcome. The essential features of an effective treatment regimen include a combination of the following steps (Penzien et al, 2002; Weeks, 1995; Weeks and Baskin, 1999):

KEY POINTS:

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A

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(1) Educating the patient, establishing expectations and a follow-up plan (This must include telling patients that they will worsen before improving.) (2) Using nonpharmacological therapies when appropriate: o Biofeedback and relaxation therapy o Cognitive behavioral therapy o Individual/family counseling as necessary o Dietary instructions, chronobiological therapy, and sleep hygiene o Daily exercise program (3) Identifying, addressing, and treating psychiatric and somatic comorbidities (4) Discontinuing all potentially offending medications and caffeine by outpatient or inpatient detoxification procedures (5) Instituting a program of acute care and preventive pharmacological therapy

A

Risk factors for migraine progression include high frequency of attacks, depression, snoring, other pain syndromes, and medication overuse. Obesity is a strong independent risk factor for migraine progression. For patients with chronic daily headache, a combination of pharmacological, nonpharmacological, behavioral, and sometimes physical interventions is usually necessary for a favorable outcome. Addressing risk factors for transformation, as well as aggressively treating those with risk factors, may be a rational preventive measure.


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Detoxification of those overusing medication is an essential step of treatment.

Discussion of the nonpharmacological treatment of chronic daily headache, as well as the treatment of comorbid disorders, is beyond the scope of this chapter. Addressing Risk Factors for Chronic/Transformed Migraine As discussed above, risk factors for developing chronic migraine have been identified. Some of them are not modifiable (gender, age, etc), but others (obesity, other pain syndromes, depression, caffeine and medication overuse, snoring) should be addressed even though it is not yet known whether this will translate into better outcomes once chronic migraine is already established (Table 7-5).

TABLE 7-5

Treatment of Medication Overuse Most studies suggest the benefit and necessity of detoxifying the patient from the overused medication (when present), followed by an intensive, longterm treatment plan. If patients discontinue their overused medications, they frequently improve considerably, and, if they do not, they are usually difficult to treat effectively (Bigal et al, 2004c; Diener et al, 1991; Grazzi et al, 2002). Basically, three outpatient approaches have been used for detoxification. The authors prefer the term ‘‘bridge’’ therapy, implying ‘‘bridging’’ from daily to intermittent use of as-needed medications. One approach is to taper the overused medication gradually while

Risk Factors for Chronic Daily Headache Development and Strategies to Address Them

Not Readily Modifiable

Modifiable

Strategies to Address Modifiable Risk Factors

Sex: female

Attack frequency

Preventive treatment

Low education/ socioeconomic status

Central sensitization

Early acute migraine interventions

Head injury

Obesity

Diet Using preventive medications that do not increase the weight

144 Medication overuse

Limiting the consumption of acute medications Preventive treatment Detoxification protocols

Stressful life events

Relaxation techniques Biofeedback Addressing depression when present

Snoring

Assessing sleep disturbances Treating sleep apnea when present


Selected Preventive Therapies for Migraine That May Be Used in the Treatment of Chronic Daily Headache

TABLE 7-6

Preventive Therapies Generic Treatment

Doses

Beta-blockers Atenolol*

25 mg to 100 mg

Metoprolol

50 mg to 200 mg

Nadolol

20 mg to 240 mg

Propranolol*

60 mg to 240 mg

Timolol Alpha2-agonists Clonidine

0.05 mg/d to 0.3 mg/d

Guanfacine

1 mg

Gabapentin

*

Levetiracetam Topiramate

*

Zonisamide

500 mg/d to 1500 mg/d

40 mg 3 times a day

Diltiazem

300 mg to 3000 mg

30 mg to 60 mg 3 times a day

Nisoldipine

1500 mg to 4500 mg

10 mg to 40 mg every day

Amlodipine

2.5 mg to 10 mg every day

50 mg to 200 mg 100 mg to 400 mg

Serotonergic agents Methylsergide* 2 mg to 12 mg Cyproheptadine 2 mg to 16 mg Pizotifen*

30 mg/d to 90 mg/d

Tricyclic antidepressants Amitriptyline* 20 mg to 150 mg 20 mg to 100 mg

Selective serotonin reuptake inhibitors Fluoxetine

10 mg to 40 mg

Sertraline

50 mg to 100 mg

Paroxetine

10 mg to 30 mg

Venlafaxine

37.5 mg to 225.0 mg

Mirtazapine

Calcium channel antagonists

Nimodipine

Monoamine oxidase inhibitors

Nortriptyline

10 mg to 30 mg

240 mg to 960 mg

Antidepressants

Phenelzine

*

Verapamil*

Anticonvulsants Divalproex sodium*

Continued

TABLE 7-6

15 mg to 45 mg

1.5 mg to 3 mg

Miscellaneous Montelukast sodium

10 mg to 20 mg

Lisinopril

10 mg to 40 mg

Botulinum 25 units to 150 units toxin A injection (intramuscular) Feverfew

50 mg/d to 82 mg/d

Chelated magnesium glycinate

400 mg/d to 600 mg/d

Riboflavin

100 mg/d

Petasites 75 mg*

75 mg bid or 50 tid

bid = 2 times a day. *Evidence for moderate efficacy from at least two well-designed placebocontrolled trials.


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Preventive treatment, associated with early acute treatment (no more than 3 times a week) and detoxification of overused medications may be the most effective treatment regimen.

an effective preventive therapy is established. The second strategy is to abruptly discontinue the overused drug, institute a transitional medication (bridge therapy) to break the cycle of headache, and subsequently taper the transitional medication. The third approach is to combine the two strategies by eliminating the rebound medication rapidly, adding a preventive medication rapidly, but also supplying a temporary bridge, to give the patient the maximum chance to improve without drastically worsening first. No matter what medication is being tapered, it is very useful to use a 3- to 7day taper of oral corticosteroids, either prednisone starting at 60 mg/d or dexamethasone starting at 4 mg/d to 12 mg/d. Alternatively, triptans or dihydroergotamines are frequently used as bridge therapies (Bonuccelli et al, 1996; Drucker and Tepper, 1998; Krymchantowski, 2003; Mathew et al, 1997; Raskin, 1986; Sheftell et al, 1999). Details on strategies for the treatment of medication overuse are discussed in the chapter Medication Overuse issue. Headache in this Establishing an Effective Preventive Treatment Most of the commonly used preventive agents for primary chronic daily headache have not been evaluated in welldesigned, double-blind studies. They are usually the same medications that are tried for migraine prevention. Table 7-6 summarizes the medications commonly used in chronic daily headache. The choice of a preventive drug is based on its proven efficacy, the

patient’s preferences and headache profile, the drug’s side effects, and the presence or absence of coexisting or comorbid disease. The clinician should select the drug with the best risk-tobenefit ratio for the individual patient and minimize the side effects that are most concerning to the patient. The reader is referred to the chapter Behavior Medicine for Chronic Headache: Overview and Practical Tools for the Practicing Physician, which covers refractory headache, and the chapter Diagnostic Testing and Secondary Causes of Headache, which covers behavioral approaches, for further discussion on the treatment of chronic daily headache, medication overuse, and behavioral and psychological factors related to these disorders. CONCLUSION Based on recent data, some episodic headaches (migraine, episodic tensiontype headaches) are now conceptualized not solely as episodic disorders, but as chronic-episodic and sometimes chronic-progressive disorders. Ongoing research and new emerging therapeutic strategies should consider this change in the conceptual model of migraine and chronic daily headaches. Preventing disease progression in migraine has already been added to the traditional goals of relieving pain and restoring patients’ ability to function. Emerging treatment strategies to prevent disease progression include risk factor modification, use of preventive therapies, and possibly the use of triptans as early as possible in the course of a migraine attack.


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Bigal ME, Rapoport AM, Tepper SJ, et al. The classification of chronic daily headache in adolescents—a comparison between the second edition of the International Classification of Headache Disorders and alternative diagnostic criteria. Headache 2005a;45:582–589. Study first suggesting that adolescents with transformed migraine have more migraine attacks than adults.

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Bigal ME, Sheftell FD, Rapoport AM, et al. Chronic daily headache: identification of factors associated with induction and transformation. Headache 2002;42:575–581. Study that shows that hypothyroidism is frequently associated with new daily persistent headache.

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Bigal ME, Tepper SJ, Sheftell FD, et al. Field testing alternative criteria for chronic migraine. Cephalalgia 2006;26:477–482. Several alternative criteria for chronic migraine were tested. Criteria that included 15 or more days of headache and 8 or more days of migraine or probable migraine performed better in clinical practice.


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Bigal ME, Tepper SJ, Sheftell FD, et al. Chronic daily headache: correlation between the 2004 and the 1988 International Headache Society diagnostic criteria. Headache 2004a;44:684–691. This study shows that the second edition of the International Headache Society criteria is still cumbersome in the classification of the chronic daily headaches despite improvement over the first edition.

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Bonuccelli U, Nuti A, Lucetti C, et al. Amitriptyline and dexamethasone combined treatment in drug-induced headache. Cephalalgia 1996;16: 198–200. Study testing a combination of a preventive medication and a bridge therapy in the management of medication overuse headache.

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Burstein R, Jakubowski M. Analgesic triptan action in an animal model of intracranial pain: a race against the development of central sensitization. Ann Neurol 2004;55:27–36. Description of the mechanisms of central sensitization.

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Burstein R, Yarnitsky D, Goor-Aryeh I, et al. An association between migraine and cutaneous allodynia. Ann Neurol 2000;47:614–624. Study showing that allodynia is the clinical hallmark of central sensitization.

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Drucker P, Tepper S. Daily sumatriptan for detoxification from rebound. Headache 1998;38:687–690.

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Grazzi L, Andrasik F, D’Amico D, et al. Behavioral and pharmacologic treatment of transformed migraine with analgesic overuse: outcome at 3 years. Headache 2002;42:483–490.

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Hagen K, Zwart JA, Vatten L, et al. Prevalence of migraine and non-migrainous headache—head-HUNT, a large population-based study. Cephalalgia 2000;20:900–906. Large epidemiological study assessing the prevalence of primary headaches, including chronic daily headaches, in Europe.


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Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders, 2nd edition. Cephalalgia 2004;24(suppl 1):9–160. Second edition of the classification system endorsed by the International Headache Society. Provides criteria for the chronic daily headaches, although the criteria for chronic migraine are still too restrictive.

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Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders. Cephalalgia 1988;8:(suppl 1)1–96. First edition of the classification system endorsed by the International Headache Society. The main criticism was the lack of criteria for the chronic daily headaches.

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Headache Classification Committee: Oelsen J, Bousser MG, Diener HC, et al. New appendix criteria open for a broader concept of chronic migraine. Cephalalgia 2006;26:742–746. Since the criteria for chronic migraine were too restrictive, the Classification Committee of the International Classification of Headache Disorders, Second Edition, elected to revise them, moving the criteria to the appendix. The new criteria now require 15 or more days of headache and 8 or more days of migraine or use of acute specific migraine medications in patients not overusing analgesics.

"

Holroyd KA, Andrasik F. A cognitive-behavioral approach to recurrent tension and migraine headache. In: Kendall PE, ed. Advances in cognitive-behavioral research and therapy. New York: Academic Press, 1982. Chapter reviewing the behavioral treatment of headaches.

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Holroyd KA, Penzien DB, Lipchik GL. Behavioral management of headache. In: Silberstein SD, Lipton RB, Dalessio DJ, eds. Wolff’s headache and other head pain. New York: Oxford University Press, 2001;562–598. Complete review of the nonpharmacological approach for the treatment of refractory headaches.

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Katsarava Z, Fritsche G, Muessig M, et al. Clinical features of withdrawal headache following overuse of triptans and other headache drugs. Neurology 2001;57:1694–1698. Seminal paper that describes the clinical features of the withdrawal period of several migraine acute medications.

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Katsarava Z, Schneeweiss S, Kurth T, et al. Incidence and predictors for chronicity of headache in patients with episodic migraine. Neurology 2004;62:788–790. Shows that in a headache clinic, the annual incidence of transformed migraine in subjects with migraine is 14%, higher than the 3% seen in the general population.

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Kruit MC, van Buchem MA, Hofman PA, et al. Migraine as a risk factor for subclinical brain lesions. JAMA 2004;291:427–434. Study showing that migraine with aura increases the chance for white matter lesions and posterior fossa subclinical ischemia.

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Lavados PM, Tenhamm E. Epidemiology of tension-type headache in Santiago, Chile: a prevalence study. Cephalalgia 1998;18:552–558. The epidemiology of chronic tension-type headache was not different than other studies in different countries.

"

Mathew NT. Transformed migraine. Cephalalgia 1993;13:78–83. Good review of the condition.

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Mathew NT, Ali S. Valproate in the treatment of persistent chronic daily headache. An open label study. Headache 1991;31:71–74. As in most open-label studies, valproate worked well in the treatment of transformed migraine.

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Mathew NT, Asgharnejad M, Peykamian M, Laurenza A. Naratriptan is effective and well tolerated in the acute treatment of migraine. Results of a double-blind, placebo-controlled, crossover study. The Naratriptan S2WA3003 Study Group. Neurology 1997;49:1485–1490. Clinical trial showing that naratriptan was effective as a rescue medication in the acute treatment of migraine. Data from this study were used to propose naratriptan as a prophylactic medication in subjects with chronic migraine.

"

Mathew NT, Reuveni U, Perez F. Transformed or evolutive migraine. Headache 1987;27:102–106. This study highlights the clinical features of migraine transformation.

"

Penzien DB, Rains JC, Andrasik F. Behavioral management of recurrent headache: three decades of experience and empiricism. Appl Psychophysiol Biofeedback 2002;27:163–181. Important paper critically reviewing the nonpharmacological management of headaches.

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Rapoport A, Stang P, Gutterman DL, et al. Analgesic rebound headache in clinical practice: data from a physician survey. Headache 1996;36:14–19. Survey among doctors with experience in chronic daily headache. A snapshot of chronic daily headache in US clinics.

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Raskin NH. Repetitive intravenous dihydroergotamine as therapy for intractable migraine. Neurology 1986;36:995–997. Proposes dihydroergotamine as an effective transitional therapy for patients with chronic daily headache and medication overuse.

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Rozen TD. New daily persistent headache. Curr Pain Headache Rep 2003;7:218–223. Review of new daily persistent headache, from clinical characterization to treatment.

"

Saper JR. The mixed headache syndrome: a new perspective. Headache 1982;22:284–286. Describes the clinical features of migraine transformation.


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Saper JR, Lake AE, Tepper SJ. Nefazodone for chronic daily headache prophylaxis: an open-label study. Headache 2001;41:465–474. Since many patients with chronic daily headache are refractory, several pilot studies tested new drugs for this syndrome.

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Saper JR, Silberstein SD, Lake AE 3rd, Winters ME. Double-blind trial of fluoxetine: chronic daily headache and migraine. Headache 1994;34:497–502. Discusses the efficacy of fluoxetine in the treatment of migraine and chronic daily headaches.

"

Scher AI, Stewart WF, Liberman J, Lipton RB. Prevalence of frequent headache in a population sample. Headache 1998;38:497–506. Epidemiological study on the prevalence of chronic daily headache in the United States.

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Scher AI, Stewart WF, Lipton RB. Caffeine as a risk factor for chronic daily headache: a population-based study. Neurology 2004;63:2022–2027.

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Scher AI, Stewart WF, Ricci JA, Lipton RB. Factors associated with the onset and remission of chronic daily headache in a population-based study. Pain 2003;106:81–89. Currently the only population-based study describing risk factors for chronic daily headache.

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Schwartz BS, Stewart WF, Simon D, Lipton RB. Epidemiology of tension-type headache. JAMA 1998;279:381–383. Describes the epidemiology of tension-type headache in the United States.

"

Sheftell FD, Rapoport AM, Coddon DR. Naratriptan in the prophylaxis of transformed migraine. Headache 1999;39:506–510. First pilot study assessing naratriptan in the prevention of chronic daily headache.

"

Silberstein SD. Tension-type and chronic daily headache. Neurology 1993;43:1644–1649. This study suggests that chronic daily headache and tension-type headache are not the same syndrome.

"

Silberstein SD, Lipton RB, Sliwinski M. Classification of daily and near-daily headaches: field trial of revised IHS criteria. Neurology 1996;47:871–875. Study presenting proposed criteria for the chronic daily headache subtypes, now used worldwide.

"

Sjaastad O, Spierings EL. ‘‘Hemicrania continua’’: another headache absolutely responsive to indomethacin. Cephalalgia 1984;4:65–70. First paper describing hemicrania continua.

"

Spierings EL, Ranke AH, Schroevers M, Honkoop PC. Chronic daily headache: a time perspective. Headache 2000;40:306–310. The authors present their personal experience in following subjects with chronic daily headache over several years.

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Weeks R. The difficult headache patient calls for a multifaceted approach. Neurol Rev 1995;3:15–16. This paper reviews the multidisciplinary approach required in the management of refractory headache syndromes, including chronic daily headache.


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Weeks R, Baskin SM. The patient who refused pharmacotherapy. In: Rapoport AM, Sheftell FD, Purdy RA, eds. Advanced therapy of headache. Saint Louis: Decker, 1999:119–124. Case-based chapter that describes the principles of the nonpharmacological treatment of migraine.

"

Welch KM, Goadsby PJ. Chronic daily headache: nosology and pathophysiology. Curr Opin Neurol 2002;15:287–295. Excellent review of the pathophysiology of chronic daily headache, correlating with implications on nosology.

"

Welch KM, Nagesh V, Aurora SK, Gelman N. Periaqueductal gray matter dysfunction in migraine: cause or the burden of illness? Headache 2001;41:629–637. Shows that migraine attacks are associated with iron deposition in the brain stem, providing a rationale for migraine progression.

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The intracranial vasculature and its innervation are essential components in the current understanding of the pathophysiology of headache.

HEADACHES AND THEIR RELATIONSHIP TO CEREBROVASCULAR AND CARDIOVASCULAR DISEASE Todd J. Schwedt, David W. Dodick

ABSTRACT The relationship between the cerebrovascular system and headache is multifaceted and incompletely understood. However, several important observations have been made. Head pain can be generated by stimulation of the intracranial vasculature. This is evident on an experimental level as well as with common vascular conditions. Headaches occur in association with ischemic strokes, cervical artery dissections, intracranial aneurysms, and following cervical or cranial vascular procedures. In addition, migraine has been identified as a risk factor for the development of vascular diseases such as ischemic stroke and cervical artery dissection. Patent foramen ovale, a structural cardiovascular disorder, is more common in patients with migraine with aura. In addition, certain rare migraine syndromes (aura without headache, hemiplegic migraine, retinal migraine, ophthalmoplegic migraine, and basilar-type migraine) may mimic stroke. Study of each of these entities will lead to a better understanding of the pathophysiology of headache and its relationship to the vascular system.

194

INTRODUCTION The intricate relationship between head pain and the cerebrovascular system has long been recognized. Initially, migraine pathophysiology was explained by a ‘‘vascular theory’’ of alterations of vasomotor tone. Migraine aura was thought to result from cerebral vasoconstriction leading to cerebral ischemia and neurological deficits. The head pain that followed was explained by reactive vasodilation. This theory persisted for many decades until the trigeminovascular system was described and recognition of the processes of neurogenic inflammation and sensitization of nociceptive trigeminal pathways

were understood. However, the intracranial vasculature and its innervation remain as essential components in our current understanding of the pathophysiology of headache. Several lines of evidence support the complex relationship between headache and the vasculature. Multiple headache types can be classified as primary vascular headaches, which are initiated by stimulation of the intracranial vasculature (Table 10-1). In addition, migraine is a risk factor for the development of vascular diseases, such as stroke and cervical artery dissection. Certain cardiovascular structural abnormalities, such as patent


TABLE 10-1

Vascular Headaches

" " " " "

Ischemic stroke

" " "

Postcarotid angioplasty

" " "

Cerebral arteritis

"

MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes)

"

Pituitary apoplexy

Arterial dissection Postcerebral angiography Postcarotid endarterectomy Postcoiling/postclipping of intracranial aneurysm

Intracranial hemorrhage Ruptured/unruptured vascular malformations

Cerebral venous thrombosis CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy)

Vestergaard et al, 1993). The majority of sensory nerves innervating the anterior circulation terminate in the trigeminal nucleus caudalis. Most of these sensory afferents project via the ophthalmic division of the trigeminal nerve (Mayberg et al, 1981). The posterior circulation sensory nerves terminate in the superior cervical ganglia and dorsal vagal ganglia with a smaller contribution from the trigeminal nucleus caudalis (Keller et al, 1985; Saito and Moskowitz, 1989). In animal models, stimulation of the intracranial arteries and dural venous sinuses results in activation of the trigeminovascular system. Superior sagittal sinus stimulation in the cat has been shown to cause measurable increases in metabolic activity and blood flow in the trigeminal nucleus caudalis, upper cervical dorsal horn,

KEY POINTS:

A

A

The intracranial vasculature is innervated by the parasympathetic, sympathetic, and sensory nervous systems. The majority of sensory nerves innervating the anterior circulation terminate in the trigeminal nucleus caudalis.

foramen ovale, occur with a higher prevalence in patients with migraine with aura. In fact, the distinction between primary cerebrovascular diseases and headache syndromes can be clouded at times with rare headache types that may mimic stroke. VASCULAR INNERVATION The intracranial vasculature is innervated by the parasympathetic, sympathetic, and sensory nervous systems (Figure 10-1). The sensory nervous system plays the predominant role in the generation of head pain. The density of sensory afferents is greatest in the proximal segments of the major intracranial arteries and in the posterior circulation (Kumral et al, 1995; O’Connor and van der Kooy, 1986;

195

FIGURE 10-1

Perivascular nerve fibers.

NA = nonadrenaline; NPY = neuropeptide Y; Ach = acetylcholine; CGRP = calcitonin gene-related peptide; NKA = neurokinin A; VIP = vasoactive intestinal polypeptide; PHI = peptide histidine isoleucine; NOS = nitric oxide synthase; V1 = first division of the trigeminal nerve; V2 = second division of the trigeminal nerve; V3 = third division of the trigeminal nerve; SPG = sphenopalatine ganglion; SCG = superior cervical ganglion; TNC = trigeminal nucleus caudalis; VII = seventh cranial nerve; SSN = superior salivatory nucleus; T2–T3 = second and third thoracic segments of the spinal cord.


" CEREBROVASCULAR/CARDIOVASCULAR DISEASE

KEY POINTS:

A

A

A

A

196

The posterior circulation sensory nerves terminate in the superior cervical ganglia and dorsal vagal ganglia with a smaller contribution from the trigeminal nucleus caudalis. Approximately 25% of stroke patients experience headache around the onset of stroke symptoms. Headaches more frequently occur with strokes that are large, in the posterior circulation, and hemorrhagic, and in patients with a history of a primary headache disorder. Headache is the most frequent presenting symptom of cervical artery dissection.

and the ventral posterior medial thalamus (VPM) (Goadsby et al, 1991). Furthermore, studies by Davis and Dostrovsky (1988) have identified thalamic neurons with orofacial inputs. These neurons are activated by stimulation of excitatory receptive fields on the face. The majority of these receptive fields are located in the distribution of the ophthalmic division of the trigeminal nerve. These same thalamic neurons are also excited by electrical stimulation of the middle meningeal artery and/or the superior saggital sinus. These data, in conjunction with a large body of experimental evidence, have led to the conclusion that nociceptive input at any portion of the trigeminovascular system, which of course includes the intracranial vasculature, may result in referred pain to the head, face, and neck. VASCULAR HEADACHES Ischemic Stroke Approximately 25% of stroke patients experience headache around the onset of stroke symptoms. (Ferro et al, 1995). In the clinical setting such headaches are commonly overlooked, often occurring in conjunction with more worrisome focal neurological symptoms. Approximately 50% of patients who develop headache with stroke have headache onset prior to the manifestation of other neurological deficits. Others develop headache coincident with or after onset of stroke symptoms. In patients with a preexisting primary headache disorder, the headache associated with stroke often resembles the patient’s preexisting headaches. For example, migraineurs may develop a migraine headache in the setting of their stroke. Other patients have onset of a new headache. These headaches are most often described as pressing or throbbing in quality, and, if unilateral, pain is usually ipsilateral to the

side of the stroke (Vestergaard et al, 1993). It has been suggested that frontal pain is more common with anterior circulation strokes and occipital pain is more common with posterior circulation strokes. Headaches more frequently occur with strokes that are large, in the posterior circulation, and hemorrhagic, and in patients with a history of a primary headache disorder (Kumral et al, 1995). Cervical Artery Dissection Headache is the most frequent presenting symptom of cervical artery dissection. Headache occurs with 60% to 95% of carotid artery dissections and about 70% of vertebral artery dissections (Silbert et al, 1995). Most commonly, headaches have a slow and gradual onset. However, about 20% of patients have a sudden and severe onset of pain consistent with a thunderclap headache (Mitsias and Ramadan, 1992). Headaches are typically located ipsilateral to the dissected artery. According to the International Headache Society (IHS), ipsilateral pain is a requirement for headache to be considered as secondary to cervical artery dissection (Headache Classification Subcommittee of the International Headache Society, 2004). Neck pain occurs in 50% of patients with vertebral artery and 25% of patients with carotid artery dissections. The median duration of headaches in both groups is 3 days. The vast majority of headaches associated with carotid dissection resolve within 1 week, while those of vertebral dissection may last up to 5 weeks. The occasional patient will develop chronic headaches. It is uncommon for patients with cervical artery dissection to present solely with headache and/ or neck pain. The majority of patients have additional neurological symptoms and signs, including amaurosis fugax, Horner’s syndrome, pulsatile tinnitus,


KEY POINT:

A

Case 10-1 A 38-year-old man with a history of migraine without aura presents after 1 day of left temporal, ear, and jaw pain. The pain started suddenly and has remained quite severe. It is described as constant, steady, and aching in quality. No associated photophobia, phonophobia, nausea, vomiting, or visual phenomena are present. However, a family member noticed that the patient’s left eyelid appeared to ‘‘droop.’’ On examination, the patient is noted to have mild ptosis of the left eyelid and pupillary asymmetry (right = 5 mm; left = 3 mm). No other neurological abnormalities are found. Magnetic resonance imaging (MRI) with diffusion images of the brain is normal. Magnetic resonance angiography of the cervical vessels reveals a long segment of tapering of the left internal carotid artery. MRI with fat saturation of the neck shows a double lumen in the left internal carotid artery that is semilunar shaped and hyperintense on T1- and T2-weighted images. Comment. Headaches are the most common presenting symptom of cervical artery dissection. No specific characteristics of dissection headaches differentiate them from other headache types. However, any new headache, especially if associated with neurological symptoms and/or signs, must prompt evaluation for underlying pathology. The majority of patients with cervical carotid artery dissections will have neurological features in addition to unilateral head, neck, or facial pain. Most commonly, these include Horner’s syndrome, amaurosis fugax, pulsatile tinnitus, dysgeusia, diplopia, or other focal neurological manifestations of stroke.

dysgeusia, diplopia, or other stroke manifestations (Case 10-1). Intracranial Aneurysms Headaches are common in patients with cerebral aneurysms prior to the diagnosis, at the time of diagnosis, at the time of treatment, and following treatment. Headache is the presenting symptom of unruptured cerebral aneurysm in approximately 33% of patients (International Study of Unruptured Intracranial Aneurysms Investigators, 1998). However, given the prevalence of headache and unruptured intracranial aneurysms in the general population and the frequency with which brain imaging is performed in patients with headache, it is not at all clear the percentage of patients in whom the aneurysm represents an incidental finding and is unrelated to the headache. Also, no specific head-

Patients with thunderclap headache must be evaluated for subarachnoid hemorrhage.

ache characteristics are associated with a high likelihood of discovering an unruptured aneurysm. Therefore, it is imperative to evaluate for associated neurological features, such as cranial nerve palsies, which provide evidence for an underlying lesion. Headache is more common in patients with aneurysm rupture, occurring in association with nausea and vomiting in 75% of patients (Fontanarosa, 1989). Headaches of subarachnoid hemorrhage are often sudden in onset and of severe intensity. Although thunderclap headaches have numerous causes, every patient presenting with such a headache should be evaluated for subarachnoid hemorrhage (Table 10-2, Figure 10-2). Headaches of subarachnoid hemorrhage are most often bilateral, and may be associated with neck stiffness and elevated body temperature. Severe pain is usually short-lived, lasting


197


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A

A

198

A history of a sentinel or warning headache is reported by 10% to 43% of patients with aneurysmal subarachnoid hemorrhage. Approximately 25% to 50% of patients with subarachnoid hemorrhage are initially misdiagnosed.

TABLE 10-2

Thunderclap Headaches

" " " " " " "

Subarachnoid hemorrhage

" " "

Cerebral vasospasm

"

Primary headache associated with sexual activity

" "

Primary exertional headache

Sentinel leak Acute hypertensive crisis Cerebral venous thrombosis Cervical artery dissection Pituitary apoplexy Spontaneous intracranial hypotension

Retroclival hematoma Primary thunderclap headache

Primary cough headache

1 to 2 hours, followed by a less severe headache of longer duration. With small hemorrhages, headaches tend to resolve after 2 to 3 days, while those with larger hemorrhages last an average of 8 days. Additional neurological symptoms and signs are the rule and often include disorientation, nausea, vomiting, altered mentation, focal motor deficits, seizures, coma, cranial nerve palsies, papilledema, ocular hemorrhages, visual field deficits, and paresthesias. A history of a sentinel or warning headache is reported by 10% to 43% of patients with aneurysmal subarachnoid hemorrhage (Polmear, 2003). A sentinel headache is an episode of headache similar to that of subarachnoid hemorrhage that occurs prior to aneurysm rupture. Such headaches develop over a few seconds, reach maximal intensity within minutes, and endure for hours to days. Certain features of subarachnoid hemorrhage headaches, such as stiff neck, focal

neurological symptoms and signs, and alteration in consciousness, are usually absent. Warning headaches tend to occur days to weeks before aneurysm rupture. They are likely caused by small aneurysmal leaks or stretching of the aneurysm wall without seepage of blood into the subarachnoid space. In many cases, recognition of these headaches as early features of subarachnoid hemorrhage would allow for surgical or endovascular intervention and avoidance of a catastrophic event. However, sentinel headaches are often ignored by the patient or physician or misdiagnosed. Approximately 25% to 50% of patients with subarachnoid hemorrhage are initially misdiagnosed (Edlow and Caplan, 2000). According to a review by Edlow and Caplan (2000), misdiagnosis occurs because of failure to recognize the spectrum of possible presentations of subarachnoid hemorrhage, lack of knowledge regarding the limitations of computed tomography (CT), failure to perform lumbar puncture, or misinterpretation of cerebrospinal fluid (CSF) tests (Case 10-2). Postcarotid Endarterectomy, Postcerebral Angiography, and Postcoiling and Postclipping of Intracranial Aneurysm New headaches are a frequent complication following cerebral artery procedures such as carotid endarterectomy, cerebral angiography, and coiling/clipping of aneurysms (Ramadan et al, 1995; Schwedt et al, 2005; Tehindrazanarivelo et al, 1992). The characteristics of each headache type differ (Table 10-3). However, headaches must have onset in close temporal relationship to the procedure and usually are located ipsilateral to the site of intervention. The presence of a primary headache disorder prior to intervention has often been recognized as a risk factor for postprocedure headaches. In fact, stimulation of the cranial vasculature can result


KEY POINT:

A

FIGURE 10-2

Migraine has been identified as a risk factor for stroke.

Evaluation of suspected subarachnoid hemorrhage. SAH = subarachnoid hemorrhage; CSF = cerebrospinal fluid.

in initiation of a patient’s usual headache type. At other times, onset of a new type of headache occurs. Following carotid endarterectomy, severe unilateral headaches, sometimes in association with seizures and contralateral focal deficits, may be manifestations of a hyperperfusion syndrome. MIGRAINE AS A RISK FACTOR FOR CEREBROVASCULAR DISEASE Cerebral Infarction Migraine has been identified as a risk factor for stroke in multiple studies.

However, study conclusions have often been contradictory, and certain subpopulations of patients with migraine are at greater risk. Epidemiological studies have shown stroke to be more common in migraineurs with and without aura. This is especially true in women younger than 45 years of age who smoke and use oral contraceptives. In this patient group, the risk of stroke is increased 3 times in migraine without aura and 6 times in migraine with aura (Chang et al, 1999; Tzourio et al, 1995). A meta-analysis of observational studies between 1966 and June 2004 concluded that the


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200

The relative risk for ischemic stroke among patients with any type of migraine headache is 2.16.

Case 10-2 A 55-year-old man presents to the emergency department 36 hours after onset of a severe headache. He reports that he was in his usual state of health and suddenly had the sensation that he ‘‘got hit with a frying pan on the back of the head.’’ Initially, his headache was 10/10 in intensity, although it decreased in severity to 8/10 after the first few hours. His headache is diffuse, pressurelike, and associated with neck pain, nausea, vomiting, and photophobia. He reports that he has had headaches intermittently in the past but nothing like his current headache. He decided to come to the emergency department because he ‘‘just can’t take it anymore.’’ On examination, his blood pressure is 170/100 mm Hg and heart rate is 120 beats per minute. He has decreased range of motion at the neck, and such movements worsen his head pain. Otherwise, no abnormalities are visible on neurological examination. CT of the brain without contrast is normal. Lumbar puncture is performed. CSF reveals 3 white blood cells/uL, 120 red blood cells in tube 1 and 122 in tube 4, a protein of 85 mg/dL, and glucose of 32 mg/dL. Visual inspection is positive for xanthochromia, and spectrophotometry reveals a bilirubin peak. Comment. The classical headache associated with subarachnoid hemorrhage is sudden and severe. Headache may be associated with nausea, vomiting, photophobia, altered level of consciousness, seizures, motor or sensory deficits, cranial nerve palsies, and ocular hemorrhages. Initial evaluation should include an unenhanced brain CT, which has its highest sensitivity in detecting subarachnoid hemorrhage in the first 24 hours (approximately 98%) and then decreases over time (50% or less at 1 week). Patients clinically suspected to have subarachnoid hemorrhage with a normal CT must undergo a lumbar puncture with CSF analysis for the presence of red blood cells and xanthochromia. When lumbar puncture is inconclusive, spectrophotometry, if available, for detection of bilirubin is highly sensitive (greater than 95%).

relative risk for ischemic stroke among patients with any type of migraine headache is 2.16 (95% confidence interval [CI] 1.89 to 2.48) (Etminan et al, 2005). The relative risk for subjects with miTABLE 10-3 Procedure

graine with aura is 2.27 (1.61 to 3.19) while it is 1.83 (1.06 to 3.15) in patients without aura. This risk does not differ when corrected for age, but the use of oral contraception increases the risk of

Postvascular Intervention Headaches Frequency Onset

Severity Duration

Carotid 60% endarterectomy

1 week

Angiography

During procedure Severe to 2 hours

33%

Aneurysm 20% coiling/clipping

Immediately postoperative to 3 days

Mild

Average 3 days; maximum 1 month 72 hours

Moderate Chronic to severe


stroke eightfold. A cross-sectional, prevalence study of Dutch adults aged 30 to 60 years suggests that this increased risk of stroke is confined to the cerebellar region of the posterior circulation (Kruit et al, 2004). In this study, the highest risk was among migraine with aura patients with one or more attacks per month (odds ratio [OR] 15.8, 95% CI 1.8 to 140.0). Despite the presence of these imaging lesions, none of the patients in this study reported a history of stroke or transient ischemic attack, and none had relevant abnormalities on neurological examination. Contradictory to these results, a recent prospective cohort study of patients aged 45 years or older participating in the Women’s Health Study concluded that migraine (with and without aura) was not associated with total, ischemic, or hemorrhagic stroke (Kurth et al, 2005). However, subgroup analyses showed a minimal increase in risk of total and ischemic stroke for migraineurs with aura (3.8 additional cases per year per 10,000 women). True migrainous infarction defines stroke that results when deficits associated with a patient’s usual migraine aura become permanent. This classification must not be used to define the patient who has their usual migraine either before or at the time of a stroke. As discussed previously, headache with stroke, which may resemble a patient’s usual migraines, occurs in approximately 25% of all stroke patients. The IHS criteria for migrainous cerebral infarction are highlighted in Table 10-4. Although the evidence is reasonably clear that migraine is a risk factor for ischemic stroke, both during and remote from the ictus, and particularly in women during their childbearing years, the mechanism(s) remains unclear. It is likely that multiple mechanisms are involved, however. Evidence suggests that regional cerebral blood flow is reduced in migraineurs during

KEY POINT:

TABLE 10-4

Migrainous Infarction— International Headache Society Criteria

"

Present attack in a patient with migraine with aura is typical of previous attacks except that one or more aura symptoms persist for >60 minutes

"

Neuroimaging demonstrates ischemic infarction in a relevant area

"

Not attributed to another disorder

A

Migraine is a risk factor for the development of cervical artery dissection.

aura. Using perfusion-weighted MRI, Cutrer and colleagues (1998) demonstrated reductions in regional cerebral blood flow of up to 50%. Platelet hyperactivity and elevation in circulating von Willebrand factor (vWF) have been reported in migraineurs (D’Andrea et al, 1982). vWF is a large, endothelial glycoprotein that causes platelet aggregation by activating the platelet glycoprotein IIb-IIIa receptors for fibrinogen. It has been reported to be an independent risk factor for stroke (Folsom et al, 1999). Migraineurs with prior stroke had significantly higher vWF antigen and activity than controls. vWF antigen (126%) and activity (130%) were also significantly higher in migraineurs without stroke (Tietjen et al, 2001). It is conceivable, therefore, that these procoagulant abnormalities may increase the risk of stroke in migraine sufferers, especially during periods of hemodynamic stress (aura) or when other risk factors are present (cigarette smoking, hypertension, oral contraceptive pill use). Cervical Artery Dissection Migraine is a risk factor for the development of cervical artery dissection. A history of migraine is reported in


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A

202

An increased prevalence of patent foramen ovale occurs in patients with migraine with aura. PFOs are found in approximately 20% to 25% of the general population and in about 50% of patients with migraine with aura.

34% to 49% of patients with cervical artery dissection (d’Anglejan Chatillion et al, 1990; Tzourio et al, 2002). Even after adjusting for age, sex, and body mass index, a history of migraine is associated with an OR of cervical artery dissection of 3.6 (Tzourio et al, 2002). A meta-analysis of risk factors for cervical artery dissection lists migraine as one of the top four risk factors (Rubinstein et al, 2005). Others include aortic root diameter greater than 34 mm (OR 14.2), relative diameter change (greater than 11.8%) during the cardiac cycle of the common carotid artery (OR 10.0), and trivial neck trauma (OR 3.8). Patients with multiple dissections have a higher OR for migraine (OR 6.7) than patients with a single artery dissection (OR 2.9) (Tzourio et al, 2002). It is unclear why migraine is a risk factor for cervical artery dissection. One suggestion is that patients with migraine have abnormalities of the extracellular matrix. Increased levels of serum elastase activity, an enzyme involved in matrix degradation, have been measured in patients with migraine (Tzourio et al, 2000). Higher levels of extracellular matrix degradation and loss of vessel wall stability may certainly be associated with the risk of cervical artery dissection. However, there have been no additional studies supporting the role of matrix degradation in patients with migraine. PATENT FORAMEN OVALE AND MIGRAINE An increased prevalence of patent foramen ovale (PFO) occurs in patients with migraine with aura. PFO is the result of incomplete fusion of the atrial septum that normally occurs shortly after birth. It acts as a persistent connection between the right and left atria, allowing for right to left shunt. Shunting may occur at rest or with elevations in right atrial pressure during Valsalva. PFO

may be detected by transesophageal echocardiography, transthoracic echocardiography, or transcranial Doppler of the middle cerebral artery with peripheral injection of agitated saline. Transesophageal echocardiography is the most sensitive, albeit the most invasive, method. PFOs are found in approximately 20% to 25% of the general population and in about 50% of patients with migraine with aura. A prevalence study using transcranial Doppler sonography with agitated saline injection evaluated for PFO in 113 patients with migraine with aura, 53 patients with migraine without aura, and 25 age-matched nonmigraine controls (Anzola et al, 1999). PFO was identified in 48% of migraine with aura patients, 23% of migraine without aura patients, and 20% of control subjects. When comparing patients with migraine with aura to patients with migraine without aura, the OR of PFO is 3.13 (CI 1.41 to 7.04). Comparison of patients with migraine with aura to controls yields an OR of 3.66 (CI 1.21 to 13.25). No significant difference in the prevalence of PFO is found between patients with migraine without aura and controls. A study focusing on decompression illness in divers and PFO also examined the frequency of migraine (Wilmshurst and Nightingale, 2001). Of 120 patients with decompression illness and right-to-left shunt detected by transthoracic contrast echocardiography, migraine with aura in daily life occurred in 42 (35%). Migraine with aura was more common in patients with large shunts present at rest (38 of 80; 47.5%) than in those with smaller shunts and those only seen after Valsalva (4 of 40; 10%) and those with no shunt (11 of 80; 13.8%). The prevalence of migraine without aura did not significantly differ between groups. The authors conclude that the size of the right-to-left shunt is related to migraine prevalence. A follow-up study from the


same investigators examined an additional 119 patients with decompression illness and right-to-left shunt (Wilmshurst et al, 2005). Results were very similar in that patients with shunts more frequently had migraine with aura than those without shunts. Once again, this association did not exist for migraine without aura and was related to shunt size. Migraine with aura was 4.5 times more prevalent in those with large shunts as compared with those with no shunt (52.9% versus 11.8%). The prevalence of migraine with aura in patients with small shunts was similar to those without shunts. The prevalence with medium-sized shunts at rest and those that are large only with Valsalva was intermediate. In the Migraine Intervention with STARFlex1 Technology (MIST) trial currently underway in the United Kingdom, 60% of 147 patients enrolled have a right-to-left shunt, the majority of which were PFOs. In addition, more than 40% of the migraine patients studied had a large shunt, 6 times greater than what would be expected in the general population. Again, PFO was the most prevalent shunt seen in these patients with migraine, accounting for more than 85% of all large shunts detected. These data confirm previous studies and indicate a strong correlation between PFO and migraine headaches (Dowson et al, 2005). Several analyses of the effects of PFO closure on migraine have reported resolution or a decrease in the frequency of headaches in patients with migraine without and with aura. However, these studies are retrospective, uncontrolled, and may include subjects undergoing PFO closure for paradoxical cerebral embolism. Although results are promising, prospective, controlled analyses of PFO closure in patients with migraine need to be completed prior to drawing conclusions about such interventions.

Thus far, the exact relationship between migraine and PFO is not clear. The two conditions, both relatively common, may be co-inherited, or PFO may be a risk factor for the development of migraine. PFO acts as a conduit for paradoxical cerebral embolism, which may potentially trigger the migraine attack and could account for the increased incidence of cerebral MRI lesions in migraine patients. HEADACHE SYNDROMES THAT MIMIC STROKE Occasionally, the clinical features of migraine may mimic stroke. This may occur during attacks of migraine with aura, aura without headache, hemiplegic migraine, retinal migraine, ophthalmoplegic migraine, and basilar migraine.

KEY POINTS:

A

A

Occasionally, the clinical features of migraine may mimic stroke. Visual symptoms, followed by sensory, aphasic, and motor symptoms, are the most frequent migraine aura manifestations.

Migraine With Aura and Aura Without Headache The manifestations of migraine aura may mimic transient ischemic attacks or stroke. An analysis of 163 patients with migraine with aura by Russell and Olesen (1996) found that visual symptoms were the most frequent aura manifestations occurring in 99% of patients. This was followed by sensory symptoms in 31%, aphasic symptoms in 18%, and motor symptoms in 16%. Patients with several different aura symptoms had visual aura with almost all attacks. The typical visual aura consists of positive phenomena (scintillations) compared with the negative symptoms (scotoma) most commonly seen with stroke. In addition, visual changes of aura may have a slow progression corresponding to cortical spreading depression and may suggest involvement of more than one arterial territory. The typical sensory aura of migraine begins in the hand and then progresses to the arm, face, and tongue (cheiro-oral distribution). Tongue involvement is rare with ischemic stroke. In addition, the sensory symptoms in


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Hemiplegic migraine must meet criteria for migraine with aura and in addition, must meet some degree of paresis.

migraine are usually positive (paresthesias) as opposed to the negative sensory symptom (numbness) of stroke. Further differentiating the two entities, sensory deficits of slow onset that are progressive in distribution are uncommon with stroke. The typical motor aura is unilateral and involves the arm and hand. Paresis may start focally and then spread to involve additional muscles, a characteristic uncommon with ischemic stroke. Although visual and sensory auras usually resolve in less than 1 hour, motor phenomena may persist for hours or days. Table 10-5 summarizes features that help distinguish migraine aura from symptoms of cerebral ischemia. The distinction between migraine aura and cerebral ischemia can be even more challenging in patients who have aura without headache. Several names have been given to this condition, including acephalgic migraine, migraine equivalent, late-life migraine accompaniment, and, most recently, according to the IHS, typical aura without headache. According to IHS criteria, manifestations should include visual and/or sensory symptoms with or without speech involvement (Table 10-6). Symptoms should have a gradual onset, be completely reversible within 1 hour,

TABLE 10-5

and have no associated headache. Patients with aura without headache often are afflicted by migraine with aura or aura with nonmigraine headaches as well. Aura without headache is most commonly seen in patients with a history of migraine with aura. Hemiplegic Migraine Hemiplegic migraine may mimic stroke. Hemiplegic migraine must meet criteria for migraine with aura and in addition must involve some degree of paresis (Table 10-7). At least one aura symptom in addition to motor weakness is present. This may include sensory symptoms, speech disturbance, visual symptoms, imbalance, diplopia, or altered mental status. If the patient has a first- or second-degree relative with hemiplegic migraine, the diagnosis is familial hemiplegic migraine. In the absence of such a family history, the diagnosis is sporadic hemiplegic migraine. Approximately 50% of cases are familial, and the other 50% are considered sporadic. The weakness of hemiplegic migraine may be mild or consistent with complete hemiplegia. Although the aura usually lasts 1 to 2 hours, it may range from 10 minutes to several days or even weeks. Generally, this is

Migraine Aura Versus Cerebral Ischemia

Feature

Migraine Aura

Cerebral Ischemia

Onset

Slow progression

Sudden

Duration

15 to 60 minutes

Often shorter

Distribution

Spreads during attack

No spread

Visual symptoms

Positive—scotoma

Negative—visual loss

Sequential symptoms

Present (eg, visual, then sensory)

Absent

History of similar attacks

Present

Often absent

History of migraine

Present

Present or absent


TABLE 10-6

International Headache Society Criteria for Typical Aura Without Headache

A. At least two attacks fulfilling criteria B through D B. Aura consisting of at least one of the following, with or without speech disturbance but no motor weakness: 1. Fully reversible visual symptoms including positive features (flickering lights, spots, or lines) and/or negative features (loss of vision) 2. Fully reversible sensory symptoms including positive features (pins and needles) and/or negative features (numbness) C. At least two of the following: 1. Homonymous visual symptoms and/or unilateral sensory symptoms 2. At least one aura symptom develops gradually over 5 minutes and/or different aura symptoms occur in succession over 5 minutes 3. Each symptom lasts 5 and 60 minutes D. Headache does not occur during aura or follow aura within 60 minutes Data from Headache Classification Committee of The International Headache Society. The International Classification of Headache Disorders. 2nd edition. Cephalalgia 2004;24(suppl 1):9–160.

followed by migrainelike head pain. Onset of hemiplegic migraine is usually between 10 and 15 years of age with a reduction in frequency commonly seen in the third decade (Ducros et al, 2001). Familial hemiplegic migraine (FHM) is inherited in an autosomal domi-

nant pattern although with incomplete penetrance. Three genes have been identified as playing a role in this disease. Type 1 (FHM1) has been linked to CACNA1A located on chromosome 19p13 (Ophoff et al, 1996). CACNA1A codes for a pore-forming subunit of the neuronal P/Q type voltage-gated TABLE 10-7

International Headache Society Criteria for Hemiplegic Migraine

A. At least two attacks fulfilling criteria B and C B. Aura consisting of fully reversible motor weakness and at least one of the following: 1. Fully reversible visual symptoms including positive features (flickering lights, spots, or lines) and/or negative features (loss of vision) 2. Fully reversible sensory symptoms including positive features (pins and needles) and/or negative features (numbness) 3. Fully reversible dysphasic speech disturbance C. At least two of the following: 1. At least one aura symptom develops gradually over 5 minutes and/or different aura symptoms occur in succession over 5 minutes 2. Each aura symptom lasts 5 minutes and 3 months

8.2

Triptan overuse headache

Triptan intake (any formulation) on 10 days per month on a regular basis for >3 months

8.3

Analgesic overuse headache

Intake of simple analgesics on 15 days per month on a regular basis for >3 months

8.4

Opioid overuse headache

Opioid intake on 10 days per month on a regular basis for >3 months

8.5

Combination analgesic overuse headache

Intake of combination analgesic medications on 10 days per month on a regular basis for >3 months

8.6

Medication overuse headache attributed to combination of acute medications

Intake of any combination of ergotamine, triptans, analgesics, and/or opioids on 10 days per month on a regular basis for >3 months without overuse of any single class

8.7

Headache attributed to other medication overuse

Regular overuse for >3 months of a medication other than those described above

8.8

Probable medication overuse headache

Medication overuse has ceased within the last 2 months but headache has not so far resolved or has reverted to its previous pattern


Medications Frequently Associated With Medication Overuse Headache In a study conducted in the authors’ center, medication intake in subjects with medication overuse headache ranged from three tablets per week to 30 per day (mean = 5.2 per day). More than 10% of patients consumed more than 10 pills per day, and 4.4% of the patients took more than 15 pills per day. The majority of patients were overusing one (35.1%) or two (36.8%) substances other than caffeine, but 31.6% were overusing three or more. Investigators contrasted the medications involved in overuse, comparing patients whose first visit was more than 5 years before the study (before 1996) with those whose first visit was between 1996 and 2001. The drugs more frequently associated with acute care medication overuse, butalbital, acetaminophen, and opioids, remained the same during both periods of time. There were statistically significant reductions in NSAIDs (25.1% versus 10.1%, P5mg>placebo

minutes even after repetitive daily use for several months (Ekbom et al, 1995). Interestingly, sumatriptan appears to be 8% less effective in chronic cluster headache than in episodic cluster headache. Sumatriptan is contraindicated in patients with uncontrolled hypertension, history of myocardial infraction, or stroke. As almost all cluster patients have a strong history of cigarette smoking, the physician must closely monitor cardiovascular risk factors in these patients. Sumatriptan nasal spray (20 mg) has been shown to be more effective than placebo in the acute treatment of cluster attacks. In more than 80 patients tested, intranasal sumatriptan reduced cluster headache pain from very severe, severe, or moderate to mild or no pain at 30 minutes in 58% of sumatriptan users versus 30% of patients given placebo on the first attack treated, while the rates were 50% (sumatriptan)

versus 33% (placebo) after the second attack treated (van Vliet et al, 2001). Sumatriptan nasal spray appears to be efficacious for cluster headache but less effective than subcutaneous injection. Sumatriptan nasal spray should be considered a cluster headache abortive in patients who cannot tolerate injections or when situationally (eg, an office setting) injections would be considered socially unacceptable. In many instances cluster headache patients may need to use sumatriptan more than once in a day for days to weeks at a time. Controversy of whether patients with cluster headache can develop analgesic-rebound headache still exists. Hering-Hanit (2000) noted that the use of daily injectable sumatriptan in four cluster patients led to a marked increase in the frequency of cluster attacks 3 to 4 weeks after initiating treatment. Three patients experienced change in the character of the cluster headache, while two patients experienced prolongation of their cluster headache period. Withdrawal of sumatriptan reduced the frequency of headaches. Even though daily sumatriptan may benefit patients with cluster headache, the goal should be to have patients cluster free on preventive medication without the need to use abortives to achieve cluster-free status. Oxygen. Oxygen inhalation is an excellent abortive therapy for cluster headache. Typical dosing is 100% oxygen given via a nonrebreather face mask at 7 L/min to 10 L/min for 20 minutes. In some patients, oxygen is completely effective at aborting an attack if taken when the pain is at maximal intensity, while in others, the attack is only delayed for minutes to hours rather than completely alleviated. It is common for a cluster patient to be headache free while on oxygen but immediately redevelop pain when the oxygen is removed. Oxygen is overall a very attractive therapy as it is


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" TRIGEMINAL AUTONOMIC CEPHALALGIAS

KEY POINTS:

A

A

174

Patients with cluster headache should not be deemed refractory to oxygen therapy unless flow rates up to 15 L/min have been utilized. Transitional cluster therapy is a short-term preventive treatment that bridges the time between cluster diagnosis and the time when the true traditional maintenance preventive agent becomes efficacious.

completely safe and can be used multiple times during the day. Large oxygen tanks are prescribed for patient’s homes, while portable tanks can be taken to the work-place. In Kudrow’s (1981) landmark study using oxygen. 75% of patients responded to 100% oxygen at 7 L/min, although only 57% of older chronic cluster headache patients had relief. A recent study (Rozen et al, 1999) documented a gender difference in response to oxygen as only 59% of female cluster patients responded to oxygen whereas 87% of men did. In almost every textbook and article written on the subject of cluster headache treatment, patients are instructed to use 100% oxygen via a nonrebreather face mask at 7 L/min to 10 L/min. The rationale behind this prescribed oxygen flow rate is unknown but has become doctrine since the Kudrow (1981) study. Prescribing higher flow rates of oxygen up to 12 L/min has recently been suggested, but no documentation reports that this may improve efficacy. The abortive effect of higher oxygen flow rates (up to 15 L/min) in cluster headache patients refractory to standard oxygen therapy is unknown. Rozen (2004) recently documented three cluster headache patients who demonstrated no response to standard oxygen therapy but had complete cluster relief when exposed to higher oxygen flow rates of 15 L/min. From this clinical observation it appears that patients with cluster headache should not be deemed refractory to oxygen therapy unless flow rates up to 15 L/min have been utilized. Zolmitriptan. Zolmitriptan is one of the second-generation triptan compounds that has shown very good efficacy in migraine. In a double-blind controlled trial, the efficacy of 5 mg and 10 mg of oral zolmitriptan was tested versus placebo in the treatment of individual cluster headache attacks

(Bahra et al, 2000). A 2-point reduction on a 5-point pain intensity scale at 30 minutes was used as a positive response end point. Forty-seven percent of patients taking zolmitriptan 10 mg had a positive response versus 40% on 5 mg and 29% on placebo. The difference reached statistical significance for 10 mg of zolmitriptan versus placebo. Significantly more patients reported mild or no pain 30 minutes after treatment with 5 mg and 10 mg of zolmitriptan (57% and 60% respectively) than after placebo (42%). The response rates for zolmitriptan are not as dramatic as that seen with oxygen or injectable sumatriptan, but this is the first oral triptan to be shown to have efficacy as a cluster abortive and is an alternative treatment option in patients who cannot tolerate injections or intranasal preparations and have either failed oxygen or find it too difficult to use in acute situations. Zolmitriptan nasal spray has also shown efficacy for treating individual cluster attacks. Other. Other effective abortives include ergotamine suppositories and dihydroergotamine (DHE) nasal spray or intramuscular injection. Transitional Therapy Transitional cluster therapy is a shortterm preventive treatment that bridges the time between cluster diagnosis and when the true traditional maintenance preventive agent becomes efficacious. Transitional preventive agents are started at the same time the maintenance preventive medication is begun. The transitional preventive agent should provide the patient with almost immediate pain relief and allow the patient to be headache free or nearly headache free while the maintenance preventive medication dose is being raised to an effective level. When the transitional agent is tapered off, the maintenance preventive agent will have


kicked in; thus, the patient will have no gap in headache preventive coverage (Table 9-2). Corticosteroids. A short course of corticosteroids is the best-known transitional therapy for cluster headache. Typically within 24 to 48 hours of administration patients become cluster free, and by the time the steroid taper has ended, the patient’s main preventive agent has started to become effective. Prednisone or dexamethasone is the most typically used corticosteroid in cluster. A typical taper would be 80 mg of prednisone for the first 2 days followed by 60 mg for two days, 40 mg for 2 days, 20 mg for 2 days, 10 mg for 2 days, and then discontinuation. There is no set manner in which to dose corticosteroids in cluster headache. Kudrow (1980) noted that prednisone provided substantial cluster pain relief in 77% of 77 episodic cluster patients and partial improvement in another 12%. Patients with chronic cluster headache did not fare as well, with only 40% of 15 patients treated showing marked improvement.

TABLE 9-2

"

Transitional Treatment Options

Corticosteroids: prednisone taper; start 60 mg to 80 mg, taper over 10 to 12 days

"

Naratriptan: (2.5 mg) one tab bid for 7 days

"

Ergotamine (2 mg): one tab at bedtime or bid for 7 days

"

Dihydroergotamine (DHE): daily intramuscular injections (1 mg every day or bid) for 1 week, intravenous infusion of DHE 1 mg tid for 3 days

"

Occipital nerve blockade

bid = 2 times a day; tid = 3 times a day.

Dexamethasone at a dose of 4 mg twice a day for 2 weeks followed by 4 mg a day for 1 week has also been shown to be effective (Anthony and Daher, 1992). However, when dexamethasone or prednisone is tapered, the cluster attacks frequently recur. Therefore, corticosteroids are primarily useful for inducing a rapid remission in patients with episodic cluster headache, although they may provide a brief respite for patients with chronic cluster headache. Long-term use of corticosteroids in these patients must be resisted. Dihydroergotamine. Intravenous DHE is an attractive transitional treatment but is more labor intensive because patients either need to be admitted or brought to an outpatient infusion center for therapy. Typically within 1 or 2 days of repetitive DHE treatment, cluster attacks stop and will not return for days to months. This allows time for a maintenance preventive agent to be started, and when the effects of the DHE wear off, the true maintenance preventive agent’s effects have already kicked in. Mather and colleagues (1991) reported the use of repetitive intravenous DHE in 54 cluster patients (23 episodic, 31 chronic). At the same time DHE was initiated, a preventive agent was also started. Onehundred percent of patients had complete relief of attacks with DHE. At 3-month follow-up, 93% of the episodic patients remained cluster free and 7% demonstrated a 50% to 74% improvement. Of the chronic cluster patients, 44% were headache free at 3 months and another 52% showed at least a 50% improvement. While a patient is on DHE therapy, sumatriptan and other vasoconstrictive agents cannot be used concomitantly. Occipital nerve blockade. Anthony (1985) was the first to report on the use of occipital nerve blockade to arrest cluster headache attacks. Mitsias and


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" TRIGEMINAL AUTONOMIC CEPHALALGIAS

KEY POINT:

A

176

Continuing a preventive agent even after the patient has gone out of cycle does not appear to prevent a subsequent cluster period from starting.

colleagues (2001) recently treated 12 patients with greater occipital nerve blocks; a total of 24 blocks were performed on 24 attacks. Twenty-three (96%) were successful in completely aborting a cluster headache cycle within 7 days. Peres and colleagues (2002) treated 14 cluster headache patients with greater occipital nerve block as transitional therapy. The mean number of headache-free days was 13.1. Four patients (28.5%) had a good response, five (35.7%) a moderate response, and five (35.7%) no response. The greater occipital nerve block was well tolerated with no adverse events. Headache intensity, frequency, and duration were significantly decreased comparing the week before with the week after the nerve block (P

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