Migraine and Related Headache Syndromes

Transcription

1 neurology Board Review Manual Statement of Editorial Purpose The Hospital Physician Neurology Board Review Manual is a peer-reviewed study guide for residents and practicing physicians preparing for board examinations in neurology. Each manual reviews a topic essential to the current practice of neurology. PUBLISHING STAFF PRESIDENT, Group PUBLISHER Bruce M. White editorial director Debra Dreger ASSociaTe EDITOR Rita E. Gould EDITORial assistant Farrawh Charles executive vice president Barbara T. White executive director of operations Jean M. Gaul PRODUCTION Director Suzanne S. Banish PRODUCTION assistant Kathryn K. Johnson ADVERTISING/PROJECT manager Patricia Payne Castle sales & marketing manager Deborah D. Chavis NOTE FROM THE PUBLISHER: This publication has been developed without involvement of or review by the American Board of Psychiatry and Neurology. Endorsed by the Association for Hospital Medical Education Migraine and Related Headache Syndromes Editor: Alireza Atri, MD, PhD Instructor in Neurology, Harvard Medical School, Assistant in Neurology, Memory Disorders Unit, Massachusetts General Hospital, Boston, MA Associate Editor: Tracey A. Milligan, MD Instructor in Neurology, Harvard Medical School, Associate Neurologist, Brigham and Women s and Faulkner Hospitals, Boston, MA Contributor: Paul B. Rizzoli, MD, FAAN Instructor in Neurology, Harvard Medical School, Associate Neurologist, Brigham and Women s and Faulkner Hospitals, Clinical Director, John R. Graham Headache Center, Faulkner Hospital, Boston, MA Table of Contents Introduction Approach to Evaluation of Headache Migraine Management Tension-type Headache Chronic Daily Headache Cluster Headache References Cover Illustration by Kathryn K. Johnson Copyright 2006, Turner White Communications, Inc., Strafford Avenue, Suite 220, Wayne, PA ,. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, mechanical, electronic, photocopying, recording, or otherwise, without the prior written permission of Turner White Communications. The preparation and distribution of this publication are supported by sponsorship subject to written agreements that stipulate and ensure the editorial independence of Turner White Communications. Turner White Communications retains full control over the design and production of all published materials, including selection of appropriate topics and preparation of editorial content. The authors are solely responsible for substantive content. Statements expressed reflect the views of the authors and not necessarily the opinions or policies of Turner White Communications. Turner White Communications accepts no responsibility for statements made by authors and will not be liable for any errors of omission or inaccuracies. Information contained within this publication should not be used as a substitute for clinical judgment. Neurology Volume 10, Part 4

2 Neurology Board Review Manual Migraine and Related Headache Syndromes Paul B. Rizzoli, MD, FAAN INTRODUCTION Headache as a symptom is nearly ubiquitous. Under certain circumstances of pattern, frequency, severity, and other factors, the symptom may qualify for a diagnosis of a primary headache disorder. These headache disorders are among the most common and most debilitating conditions known, 1,2 and their effect on productivity and quality of life is staggering. In the United States alone, estimates are that 23 million individuals have severe, limiting migraine, resulting in lost productivity of more than $1 billion per year and accounting for 10 million physician office visits annually. 3 Under other circumstances, the symptom of headache may reflect an underlying illness or condition (ie, a secondary headache). Differentiating between primary and secondary headache is the first and most critical step in the diagnostic process. Headache syndromes, especially primary headache syndromes, will be encountered by practitioners in nearly every aspect of clinical medicine. This review focuses on the classification, diagnosis, and management of some of the more common primary headache syndromes. CLASSIFICATION OF HEADACHE The current most widely used system for classifying headache is that of International Headache Society (IHS), the International Classification of Headache Disorders, Second Edition (ICHD-II), revised in The ICHD-II is designed primarily to afford diagnostic consistency for research purposes. As such, the system classifies headache based on characteristics alone without regard to associated features such as age, sex, family history, or life stressors. Part 1 classifies primary headache (ie, those with no other known cause) as 1 of 4 main types: migraine, tension-type headache, cluster headache and other trigeminal autonomic cephalalgias (TAC), and other primary headaches. Migraine is further subclassified as migraine with or without aura (which can include either the traditional visual aura or sensory symptoms), retinal migraine, complications of migraine, or probable migraine. Tension-type headache is further subclassified as infrequent, frequent, chronic, or probable. Cluster headaches are grouped with the relatively rare conditions of paroxysmal hemicrania, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT syndrome), and probable TAC. Finally, other primary headaches include both common and uncommon conditions: stabbing, cough, exertional, hypnic, and thunderclap headaches; headache associated with sexual activity; hemicrania continua; and new daily persistent headache. Secondary headaches, of which there are many, comprise Part 2 of the ICHD-II. Nonetheless, the major utility of the system resides in Part 1, where most of the research efforts have typically been directed and research in headache surged after the implementation of the original IHS system. From a clinical standpoint, the ICHD-II classification system is difficult to apply in practice. For example, headache types such as chronic daily headache and menstrual migraine do not appear in the system, although these diagnoses remain in wide clinical use. Menstrual migraine does not easily fit into the system because it includes a trigger in the individual patient and thus is not descriptive of the headache itself; it has since been added to the appendix of the 2004 classification. Chronic migraine and chronic tension-type headache appear in the system, along with a category for new daily persistent headache, but not chronic daily headache. 5 COMMON HEADACHE SYNDROMES: EPIDEMIOLOGY AND CLINICAL CHARACTERISTICS Migraine Migraine is a common, chronic, and in some instances progressive genetic neurologic disorder characterized by episodic symptomatology often triggered by environmental variables that, as a common thread, tend to disturb the migraineur s homeostatic balances. Thus, changes in weather, time zone, sleep states, hormonal status, and stress level all tend to be reported as triggers. The potency of the trigger seems to reflect the speed and magnitude of the change (eg, a rapidly approaching low pressure system is more often reported as a trigger than is a slowly developing high pressure system). The menstrual trigger, as another example, is attributed to the rapid fall in estrogen levels just prior to menses. 6 Hospital Physician Board Review Manual

3 Most episodes of migraine typically but not always include headache among the symptoms. Varied clinical presentations are recognized, although stereotyped features often characterize migraine events in the individual patient. Most commonly, the headache is characterized as a lateralized (but not side-locked), moderate to severe throbbing pain lasting hours to days. The headache is associated with photophobia and phonophobia and often with nausea but less likely with vomiting. Incidence (rate of onset of new cases) studies indicate that migraine onset is earlier in boys than girls. 3 In males, the incidence peaks around age 10 years and declines thereafter, with new-onset migraine becoming uncommon in males in their 20s. The incidence in females increases dramatically at or after menarche, surpassing the incidence in boys, and peaks in the later teens. 3 Prevalence (portion of the population with migraine) is better studied. Overall migraine prevalence is highest among those between the ages of 25 and 55 years. In this age-group, migraine is more common than diabetes, hypertension, and asthma combined. 7 Peak prevalence of migraine in the United States is approximately 18% in women and 6% in men, 3 for an approximate total of 28 million Americans. Disability studies show that about half of migraine patients are severely disabled during an attack and 75% of patients have some reduction in functional ability during an attack. 8,9 Thus, migraine is a common and disabling condition affecting about a quarter of the U.S. population during their most productive years, producing a significant burden upon the patient, the health care system, and society as a whole. Cluster Headache Cluster headache, in contrast to migraine, is for the most part strictly unilateral and periorbital in location and is severe one of the most severe of any described pains. The episodic attack is shorter than a migraine, lasting minutes to hours, but may recur more than once a day. Attacks tend to cluster for weeks or months and then not to recur for periods up to a year or more. Characteristic signs of ipsilateral autonomic dysfunction including conjunctival injection, lacrimation, rhinorrhea, or eyelid edema tend to accompany the pain (Figure). Cluster headache occurs throughout the world. Prevalence studies vary, with a high of about 400 cases per 100,000 in the United States 10 to a low of 56 per 100,000 in San Marino. 11 Although a relatively rare form of primary headache, cluster headache is as common or more common than multiple sclerosis, an illness that has an estimated prevalence of 400,000 cases Figure. Patient during a right-sided cluster headache, showing ipsilateral autonomic changes. in the United States per the National MS Society (www. nationalmssociety.org/about%20ms.asp) and that receives significantly greater public attention. Tension-type Headache When mild and infrequent, tension-type headache is generally not considered a health issue. An infrequent, mild tension-type headache is often regarded as a regular or normal headache, for which care is not generally sought. It is usually bilateral and often frontal in location and is not usually throbbing. Typically missing are the associated sick features of nausea, photophobia and phonophobia, and exertional increase that characterize migraine. However, there is significant overlap between the 2 types of headaches, and many individuals describe both migraine and tension-type headache at different times. When frequent (1 15 headaches per month) or chronic (> 15 headaches per month), tension-type headache constitutes a major health problem. Prevalence of episodic tension-type headache is approximately 38% of the population and of chronic tension-type headache is 2% to 3%. 12 APPROACH TO EVALUATION OF HEADACHE The first goal in the diagnosis of headache is to differentiate primary from secondary headache. The history and physical examination are the primary elements used to make the diagnosis, supplemented with Neurology Volume 10, Part 4

4 Table 1. Key Components of the Headache History Past history of headache-related symptoms during: Childhood Grade school Teenage years (menarche) After high school (ie, 20s, 30s) Pregnancies Current headache history Features of a typical headache Onset (eg, sudden or slow, with waking, wakes from sleep, onset in afternoon) Aura, prodrome, postdrome Frequency, severity, duration Character of the pain (eg, steady, throbbing, sharp, dull) Associated symptoms (eg, photophobia, phonophobia, nausea, vomiting) Triggering, aggravating/alleviating features (eg, weather change, menstrual period, stress, time change, foods) Sleep pattern (fragmented and/or nonrefreshing sleep?) Activity level (gauge of headache severity; what does headache keep patient from doing?) Family history of headache testing as appropriate. The following case illustrates when to worry and when not to worry a critical distinction when evaluating the headache patient. CASE 1 PRESENTATION A 34-year-old woman is referred to a neurologist for evaluation of a headache that has persisted for the past 3 months. The headache occurs daily and is associated with nausea without vomiting, photophobia, and phonophobia. The patient reports that the headache at times has awakened her at night and is present when she wakes up. She smokes and takes oral contraceptives. A detailed headache history from the patient is positive for childhood carsickness and for an onset of headaches with migrainous features when the patient was in her 20s. The headaches have slowly progressed in frequency and severity over the years, culminating in her current pattern. The patient also reports that her mother and sister have experienced recurrent sick headaches. Aside from being obese, the patient s physical examination is normal, including vision and funduscopic examination. What questions are important in determining how worrisome this patient s headache is? Headache History A thorough headache history is the most important feature in the initial evaluation of the headache patient and will set the stage for much of the decision making to follow. A structured, systematic approach to obtaining the history will ensure that the physician has a platform on which to base a diagnosis of primary headache. An incomplete history increases the possibility of an erroneous diagnosis of a secondary headache, which unnecessarily heightens diagnostic concern. Thus, the history is vital not only to avoiding the pitfalls of headache diagnosis but to avoiding unnecessary, costly, and possibly risky evaluations. It is useful to obtain a time-based headache history from the patient (Table 1). The headache history should start with questions about childhood headache symptoms (carsickness, abdominal pain, headache), followed by detailed questioning for migraine-related symptoms during each level of school and then each decade beyond school, with attention as appropriate to headache associated with such events as menarche, pregnancy, marriage, job changes, and the like. The current headache history is then added to this foundation. Family history of migraine is also clinically useful and a supportive feature in the evaluation. Danger Signs Emergent causes of headache should be kept in mind during every headache evaluation. 13 Headache that is associated with systemic symptoms, secondary risk factors, or change of mental status; new-onset headache in an elderly patient; or a change in an established headache pattern may suggest developing intracranial pathology or a systemic process (eg, temporal arteritis). Such findings always warrant further evaluation and perhaps hospital admission. Guidelines from the American Academy of Neurology (AAN) further suggest that headache that rapidly increases in frequency, is associated with discoordination or focal neurologic signs or symptoms, or that awakens the patient from sleep could also signal intracranial pathology as the cause and therefore may warrant further investigation. 14 Physical and Neurologic Examinations In most primary headache patients, the physical and neurologic examinations will be normal. Components of these examinations that may help in differentiating primary from secondary headache include vital signs (fever and hypertension), funduscopic examination (papilledema from increased intracranial pressure or a focal mass lesion), palpation of the head and neck for tenderness Hospital Physician Board Review Manual

5 (noted in some tension-type headaches), range of motion of the neck (cervicogenic headache and meningismus), deep tendon reflexes and Babinski testing (focal intracranial process), and gait and balance testing (eg, to detect ataxia associated with posterior fossa pathology). What is the differential diagnosis at this point? Differential considerations in this case could include a new-onset migraine, pseudotumor cerebri or another cause of increased intracranial pressure, or intracranial (arterial or venous) vascular disease. Given the patient s overweight condition, history of smoking, and oral contraceptive use and the fact that pseudotumor cerebri has been noted in the absence of papilledema, 15 it would not be unreasonable to consider a diagnosis of pseudotumor. Furthermore, the headache in intracranial hypertension may have features of migraine. 16 However, the patient s headache history (symptoms, timeline, family history) would lead one to focus more on a primary headache syndrome as the most likely diagnosis, in particular a form of migraine. The presumptive diagnosis here would be migraine that has transformed into a daily pattern. Transformed migraine in this patient indicates that there is a prior history of intermittent headache meeting the criteria for (probable) migraine without aura that has progressed to a daily or near-daily frequency. Often, with development of chronicity, some of the migrainous features become less distinct. The ICHD-II criteria for diagnosis of migraine without aura are shown in Table 2. What role do diagnostic tests play in the evaluation of patients with headache? Is any testing indicated for this patient, or should initiation of therapy for presumed migraine be the next step? Diagnostic Testing Given the frequency of migraine, the routine use of diagnostic studies in its evaluation would be extremely burdensome and thus is discouraged. When needed, the most useful studies are structural, mainly magnetic resonance imaging (MRI) and computed tomography (CT). From a clinical perspective, MRI of the brain overall provides more information than does CT, although the latter may be more readily available and more appropriate in the emergency department if hemorrhage is a concern. With specific relation to headache, MRI can show relevant findings such as an Arnold-Chiari malformation (which can produce headache), meningeal enhancement (which can be associated with lowpressure headache), hydrocephalus, tumor (intra- or Table 2. ICHD-II Diagnostic Criteria for Migraine Without Aura A. At least 5 attacks fulfilling criteria B D B. Headache attacks lasting 4 72 hours (untreated or unsuccessfully treated) C. Headache has at least 2 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, climbing stairs) D. During headache at least 1 of the following: 1. Nausea and/or vomiting 2. Photophobia and phonophobia E. Not attributed to another disorder Reproduced by permission of Blackwell Science, Inc., from International Headache Society. International classification of headache disorders. 2nd edition. Cephalalgia 2004:24 Suppl 1:24 5. extra-axial or extracranial), sinus disease, stroke-like changes (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy [CADASIL]), arteriovenous malformation, angioma, or an unruptured aneurysm (which although not often a cause of headache is nonetheless of critical diagnostic importance). From an evidence-based perspective, current AAN guidelines suggest that neuroimaging should be considered in patients with nonacute headache and an unexplained abnormal finding on the neurologic examination ; there was no clear evidence to establish MRI or CT as the preferred imaging modality. 17 Weaker evidence supports the use of imaging in patients with atypical headache features, when the strict definition of a primary headache disorder is not met or when there is a coexisting risk factor. Although electroencephalograms often show minor nonspecific abnormalities in migraine patients, this procedure is not recommended as a routine diagnostic test for migraine. 18 Lumbar puncture retains a small but significant role in the headache evaluation to identify acute or chronic infections or inflammatory conditions and as an adjunctive method to evaluate for the presence of hemorrhage. Regarding the case patient, a reasonable approach would be to treat her initially for migraine and, if treatment fails to produce the expected response, to consider further evaluation at that point. If an evaluation lacks all the features necessary for a confident diagnosis of migraine, probable may be added to the diagnosis. Neurology Volume 10, Part 4

6 Table 3. Goals of Acute Migraine Management Treat attacks rapidly and consistently without recurrence Restore the patient s ability to function Minimize the use of back-up and rescue medications* Optimize self-care and reduce subsequent use of resources Be cost-effective for overall management Have minimal or no adverse events Adapted with permission from 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 [published erratum appears in Neurology 2000;56:142]. Neurology 2000;55:756. *A rescue medication is used at home when other treatments fail and permits the patient to achieve relief without the discomfort and expense of a visit to the physician s office or emergency department. The term probable migraine has replaced the older designation, migrainous. Both terms were chosen to denote a migraine attack that lacks 1 essential diagnostic criterion. Most authors believe this is a form of migraine that can respond in similar fashion to migraine that meets all diagnostic criteria. Therefore, it seems safest to be guided by a careful history and physical examination, followed by a plan for treatment and an assessment of the response. CASE 1 CONCLUSION The patient is started on acute and preventive pharmacotherapy for her daily headache and remains improved when seen in follow-up 1 year later. MIGRAINE MANAGEMENT CASE 2 PRESENTATION A 47-year-old woman, referred to a neurologist, presents for evaluation of frequent (3 4 per week) headache. She has been using over-the-counter analgesics to treat her headaches but reports only minimal benefit from the medications. The patient does not recall any significant childhood headache or related symptoms apart from carsickness, and she reports no family history of migraine. She completed 6 pregnancies without headache and recalls no instances of menstrual headache in her 20s. In her early 30s, she began to experience frequent headaches described as lateralized retro-orbital pains. The headaches are preceded by scintillating scotomata and associated with nausea and photophobia. Her medical history is otherwise notable only for mild asthma treated with albuterol as needed. She does not smoke and is not on any hormone therapy. Her general physical and neurologic examinations are normal. What is the most likely diagnosis for this patient s headache syndrome? Using the ICHD-II, this patient would qualify for a diagnosis of migraine with aura. Aura includes fully reversible visual, sensory, or speech disturbances. Visual and sensory disturbances may be positive (flickering lights, pins and needles) or negative (visual loss, numbness) in character. Unusual features in the case patient s history include a relatively late onset of headache and the lack of a family history. Each of the primary headache classifications includes a qualification that the symptoms not be explained by any other condition, and, although this is very likely a primary headache condition, a positive response to acute and/or preventive therapy for migraine would provide additional reassurance. Of note, this patient reports no history of menstrual worsening of her headache. Patients with menstrual-related migraine (ie, headaches that are present at other times but are worsened by the menstrual cycle, usually at menses) or menstrual migraine (ie, headaches that occur only in relation to the menstrual cycle) usually present with a pattern of migraine without aura. Thus, if this patient had reported a menstrual-related headache pattern, she probably would have also reported that her menstrual headaches lacked an aura. CASE 2 CONTINUED The patient is advised that she is likely experiencing migraine and therapy is recommended to see if her headache improves. Because of the frequency of her headache, preventive therapy with verapamil is recommended. Although open to trying migraine prophylaxis, the patient is concerned about how to manage her headaches when they occur. What are options for acute treatment of migraine symptoms? Was verapamil an appropriate choice for migraine prevention in this patient? Acute Symptomatic Therapy Acute migraine management should ideally meet the goals outlined in Table 3. Acute treatment of migraine should be tailored to the severity of the attack and the nature and degree of associated symptoms (stratified care). 14 It may be useful for the patient to have an array of therapies to help manage the spectrum of symptoms. Flexibility in approach is useful. For Hospital Physician Board Review Manual

7 example, if the patient s history is that of headache that builds quickly, there is not much room for error in the selection of a treatment and an early dose of a triptan medication may be warranted. If the history includes early severe nausea that could complicate later management due to gastroparesis, treatment may need to be initiated with an antiemetic. Generally, treatment should be adequate for the individual event, and early and aggressive management is recommended in order to stop the event and return the patient to a pain-free state. However, it should be noted that early and frequent use of overly strong therapies can lead to early depletion of medication supply, medication overuse, and possible toxicity. Accepted acute therapies for migraine are shown in Table The triptans, of which sumatriptan was the first widely available agent, dominate Group 1 as strong and specific therapies for the severe acute headache. Monthly quantities are limited to avoid possible toxicity, especially cardiac ischemia, and also due to cost. The triptans have proved remarkably safe and efficacious in clinical practice. 19 Ergot preparations remain available and effective and have a role in management but probably as a group produce somewhat more side effects than do the triptans. Moderate headaches are often well managed with anti-inflammatory medications. Combination analgesics containing butalbital are useful for mild to moderate pain, but their use should be limited and monitored to avoid overuse. As mentioned, antiemetics may play an adjunctive role. Regular use of narcotic analgesics is discouraged in the acute management of headache as their efficacy is limited and the risks are high. Narcotics are used as rescue medications in some circumstances. Preventive Therapy Frequent headache is one of the indications of the need to add daily preventive therapy to acute symptomatic therapy for migraine. Preventive therapy can also be considered when the frequency of headache rises above approximately 2 per month, a frequency that is present in more than half of migraine patients. 20 Other indications for prophylaxis include headache of long duration (> 48 hours), disabling headache, or prolonged aura. If acute symptomatic medications are poorly tolerated, contraindicated, or subject to abuse, prophylactic therapy may be indicated. Preventive therapy combined with acute symptomatic therapy for migraine clearly improves outcome, reduces associated disability, and decreases medical costs compared with acute symptomatic therapy alone. 21 General principles of preventive therapy are as shown in Table Table 4. Selected Acute Symptomatic Therapies for Migraine Group 1 (best evidence*) Specific All triptan medications PO, SC, IN DHE IV plus antiemetic; DHE IV, IN, IM, SC without antiemetic Nonspecific Acetaminophen, aspirin, plus caffeine PO Aspirin PO Ibuprofen PO Naproxen sodium PO Prochlorperazine IV Group 2 (moderate evidence) Acetaminophen plus caffeine PO Butalbital, aspirin, caffeine, plus codeine PO Chlorpromazine IM, IV Metoclopramide IV Isometheptene PO Naproxen PO Prochlorperazine IM, PR Group 3 (conflicting evidence) Butalbital, aspirin, plus caffeine PO Metoclopramide IM, PR DHE = dehydroergotamine; IM = intramuscular; IN = intranasal; IV = intravenous; PO = oral; PR = rectal; SC = subcutaneous. *Evidence from double-blind, placebo-controlled studies. Choices for migraine prophylaxis include a wide variety of medications (Table 6), including β-adrenergic blockers (propranolol, metoprolol, timolol), calcium channel blockers (verapamil), tricyclic antidepressants (primarily amitriptyline), and antiepileptic agents (valproate, topiramate). 14 Although there is no clear triage for treatment, it is not uncommon for verapamil or propranolol to be the first choice for prevention of migraine with aura. 22,23 Given the case patient s history of asthma, verapamil would be preferred over propranolol. CASE 2 CONTINUED The patient is started on daily verapamil, with antiinflammatory medications prescribed for mild to moderate headaches and a triptan prescribed for treatment of more severe attacks. The patient obtains good results from this regimen. About 10 years after diagnosis, the patient experiences what she initially perceives as a change in her headache pattern, with a persistent visual aura and only a mild associated headache. She had previously Neurology Volume 10, Part 4

8 Table 5. General Principles of Preventive Medication Use Medication use Initiate therapy with medications that have the highest level of evidence-based efficacy Initiate therapy with the lowest effective dose of the drug; increase dosage slowly until clinical benefits are achieved in the absence of, or until limited by, adverse event Give each drug an adequate trial; it may take 2 to 3 months to achieve clinical benefit Avoid interfering medications (eg, overuse of acute medications) Use of a long-acting formulation may improve compliance Evaluation Monitor the patient s headache through a headache diary Re-evaluate therapy; if after 3 to 6 months headaches are well controlled, consider tapering or discontinuing treatment Take coexisting conditions into account* Select a drug that will treat the coexistent condition and migraine, if possible Establish that the treatments being used for migraine are not contraindicated for the coexistent disease Establish that the treatments being used for coexistent conditions do not exacerbate migraine Beware of all drug interactions Adapted with permission from 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 [published erratum appears in Neurology 2000;56:142]. Neurology 2000;55:756. *Comorbid/coexisting conditions that are more common in persons with migraine include stroke, myocardial infarction, Raynaud s phenomenon, epilepsy, and affective and anxiety disorders. These conditions present both treatment opportunities and limitations. experienced typical scintillating scotomata followed by headache. The new pattern consists of recurrent flashing lights. She then develops a persistent visual field cut, for which she is evaluated. MRI of the brain shows a new left occipital stroke. Is there an association between this patient s stroke and her migraine history? What is the next step in the evaluation? There appears to be an association between stroke and migraine, although multiple epidemiologic studies have produced conflicting results and the resulting picture is a bit muddled. Convincing case-controlled studies show some increased risk in women smokers with migraine who also use oral contraceptives 24 ; however, even in these special circumstances the risk of stroke is very low. Stroke may occur in a patient with a history of migraine, or, as in this case, the stroke may seem to Table 6. Selected Preventive Therapies for Migraine* Group 1 (best evidence/efficacy with least side effects) Amitriptyline Divalproex sodium Propranolol/ timolol Topiramate Group 2 (moderate evidence/ efficacy/ side effects) Atenolol/ metoprolol/ nadolol Verapamil Aspirin Ketoprofen Naproxen/ naproxen sodium Fluoxetine Gabapentin Feverfew/ magnesium/vitamin B 2 Group 3 (clinical evidence of efficacy only) Bupropion Imipramine Mirtazepine Nortriptyline Paroxetine Sertraline Venlafaxine Cyproheptadine (especially in children) Indomethacin (in certain headache subtypes) *Groups are based on evidence, efficacy, and side-effect profile. emerge from or mimic aspects of the patient s acute migraine. In such an instance, the diagnosis of migrainous infarction is used. Notwithstanding this possible association, the recommended evaluation in this patient would be the same as in any patient with new-onset stroke. CASE 2 CONTINUED Further evaluation of the patient discloses a patent foramen ovale (PFO) by transthoracic echocardiogram. What is the relationship between PFO and migraine? How should this patient be managed? A recent study has reported a higher than expected frequency of PFO in patients with a history of migraine with aura. 25 This association may not extend to other forms of migraine or to tension-type headache. There may also be an association between PFO, migraine with aura, and stroke. 26 Thus, it is not a complete surprise that these features occurred together in this patient. In managing the case patient, it is reasonable to evaluate her for closure of the PFO based on the suspicion Hospital Physician Board Review Manual

9 that the stroke was related to the PFO. In the meantime, there does not seem to be a contraindication to adding aspirin for secondary stroke prevention, although there is no clear evidence that it will be protective. Her migraines themselves have been fairly well controlled; therefore, a change in her headache management is not indicated. There has been a suggestion that closure of the PFO improves migraine control, sometimes dramatically. 27 However, the evidence so far is not strong enough to allow recommendation for closure of a PFO as a therapeutic strategy for migraine. Should patients diagnosed with migraine with aura be routinely evaluated by echocardiography to exclude the possibility of PFO? The case patient, with documented migraine with aura, subsequently developed an occipital stroke, evaluation of which disclosed a PFO. Migraine and PFO are both common conditions that are likely to coincide, although perhaps more frequently than can be explained by chance. As PFO by itself is often thought not to require therapy, most individuals with both conditions can be managed simply with attention to the migraine. Thus, routine evaluation for PFO a condition that will not require management is not recommended. TENSION-TYPE HEADACHE If migraine with or without aura is viewed as being at one end of a pathologic spectrum, tension-type headache might lie at the other end (ie, 2 clinical expressions of the same underlying pathology). One argument for this view is that tension-type headache may occur along with migraine in the same individual. In patients with both diagnoses, tension-type headache may share some of the characteristics of migraine, including clinical symptoms, family history, and an often complete response to migraine-specific acute symptomatic medications. Another view, however, simply has the 2 common headache types, each with a presumed separate pathology, occurring in the same individual. Either way, headache characteristics and qualities may form a continuum in a given individual, which the following case illustrates. CASE 3 PRESENTATION A 31-year-old right-handed woman with a previous diagnosis of migraine presents to a new neurologist to establish follow-up after moving to the area. She had requested transfer of her records, but they had not arrived at the time of her initial visit. The patient denies childhood carsickness, abdominal pain, or headache but reports a positive family history of migraine in her mother and sister. Throughout grade school and junior high school, the patient did not note particularly significant headache, although after menarche, she developed bad menstrual cramps. Headaches began in high school and continued through college but were easily controlled by overthe-counter medications. Frequency was about 2 per month. The patient cannot recall if the headaches were related to her menstrual cycle and she can only vaguely describe them, but she believes that they were always on the left and generally were not limiting. In her 20s, she began to experience migraine characterized as a more severe, limiting headache. She recalls no specific triggers but reports general life changes during this time. She was evaluated neurologically and was tried on multiple medications. She does not recall a specific diagnosis, and she never settled on any particular regimen of medication. Head CT and MRI were reportedly normal. She is currently experiencing 2 headaches per month, with a constant dull underlying daily headache in between. The severe headaches occasionally occur as a prodrome of neck pain followed by development of a steady, boring, sharp or stabbing left temporal pain not increased by activity, unassociated with aura, and lasting up to 2 days. Local pressure in the left temporal region may transiently relieve the pain. Associated symptoms include occasional nausea. The patient reports that her stress level influences her headaches. With regard to stress, she says that she worries a lot about the future and her career. In addition, she has experienced occasional panic attacks. She describes her sleep as unrefreshing and says she is usually tired during the day. What is the diagnosis in this patient? Based on the information obtained so far, the case patient would not fulfill the criteria for diagnosis of migraine without aura. Perhaps details in her past medical records would clarify the issue. However, it is common for more than 1 headache type to be present in an individual, either at the same time or over time. This patient s more recent symptoms are suggestive of a frequent episodic tension-type headache (Table 7), perhaps beginning to develop into a chronic tension-type headache. Depending upon how the history of daily pain is factored in, she could qualify for a diagnosis of either frequent episodic or chronic tension-type headache. CASE 3 CONTINUED The initial evaluation of the patient also reveals a past medical history notable for depression and anxiety Neurology Volume 10, Part 4

10 Table 7. ICHD-II Diagnostic Criteria for Frequent Episodic Tension-type Headache A. At least 10 episodes occurring on 1 or more but less than 15 days per month for at least 3 months ( 12 and <180 days per year) and fulfilling criteria B D B. Headache lasting from 30 minutes to 7 days C. Headache has at least 2 of the following characteristics: 1. Bilateral location 2. Pressing/tightening (non-pulsating) quality 3. Mild or moderate intensity 4. Not aggravated by routine physical activity such as walking or climbing stairs D. Both of the following: 1. No nausea or vomiting (anorexia may occur) 2. No more than one of photophobia or phonophobia E. Not attributed to another disorder Adapted with permission of Blackwell Science, Inc., from International Headache Society. International classification of headache disorders. 2nd edition. Cephalalgia 2004:24 Suppl 1:38. but negative for asthma, bipolar disorder, cerebrovascular disease, diabetes mellitus, epilepsy, or other conditions. Physical examination shows a head forward posture and bilateral stylomastoid region tenderness to palpation. What other features may be contributing to the headache symptoms in this patient? Associated musculoskeletal conditions (eg cervical spondylosis, cervical degenerative disease, chronic cervical strain) are often present in headache patients and can complicate headache treatment. 28 Note that musculoskeletal complaints are not part of the diagnostic criteria for tension-type headache and here act simply as comorbid features. Attention to musculoskeletal issues as well as the headaches seems to improve the overall chances of treatment success. 29 In this patient, postural changes and muscle tenderness were both present. Physical therapy may have a role in this patient s management. The patient also reported daytime somnolence and sleep symptoms, which may represent a mild nonspecific sleep disorder associated with migraine or could suggest a separate and confounding sleep disorder. If symptoms do not improve with treatment of the migraine, overnight polysomnography can be considered. Depression and anxiety are both comorbid with migraine but are not an extension of migraine. 30 Treatment of these conditions may be required, however, in order for the migraine therapy to be fully effective. How should this patient be managed? Preventive Therapy Certainly, daily preventive therapy is indicated for this patient. Choices would be the same as those outlined for migraine prophylaxis (Table 6). As previously noted, no hard and fast rules exist for determining which preventive medications to use in which situations. However, amitriptyline might be a reasonable first choice for this case patient. Amitriptyline is effective preventive therapy in all forms of headache but is considered more often in tension-type headache. 31 As with all the preventive medications, the mechanisms of action with amitriptylene are multiple, and which effects specifically are responsible for the antiheadache effect are unknown. What does seem clear is that the amitriptyline is not functioning as an antidepressant as it treats the headache. Effective doses appear to be in the range of 10 to 75 mg nightly. At the antidepressant doses of approximately 100 mg or more nightly, the drug does not appear to control headache. In fact, the migraine pattern may reappear if the medication is pushed into the antidepressant range. In addition to reduction in headache, amitriptyline seems to treat the associated sleep disturbance in migraine and is helpful in preventing the headaches that are reported with waking. The major adverse effect associated with the medication is persistent drowsiness on waking that can linger into the day. This side effect may necessitate stopping the medication, although reducing the dose to 5 or even 2.5 mg (by breaking the tablet) can result in efficacy with tolerable side effects. Even if amitriptyline does not control the headache on its own, it may be best to leave it in place to treat the sleep disorder and add another preventive medication. Other tricyclic medications such as nortriptyline and imipramine are effective but to a lesser degree. Acute Symptomatic Therapy Acute symptomatic therapy is almost always indicated in addition to preventive therapy, although typically these acute therapies appear more effective than before (most likely because the severity of the headache is reduced by the preventive therapy) and are needed less frequently. For mild to moderate pain, an anti-inflammatory medication (typically a nonsteroidal anti-inflammatory drug) will suffice. This agent also might be mixed with something mild such as acetaminophen/dichloralphenazone/ isometheptene. The combination of agents may be more effective at aborting a headache than any single agent alone. For more severe headaches, a triptan medication is indicated. 10 Hospital Physician Board Review Manual

11 Nonpharmacologic Therapy Nonpharmacologic therapy, in particular physical therapy, may also be indicated for this patient. 32,33 In addition, biofeedback, acupuncture, and cognitive behavioral techniques all have demonstrated efficacy, 32,34 but these are neither universally available nor reliably covered by insurance. Moreover, it appears that their efficacy develops only over time and is usually dwarfed by response to pharmacotherapy. Therefore, these approaches should probably be reserved for extremely motivated or medication-averse patients. CHRONIC DAILY HEADACHE A challenging condition to treat, chronic daily headache is perhaps the most common reason for referral to a headache center, although these patients can also be found in general neurology clinics. The methodology to study these patients has improved, and with resulting increased attention and effort, our understanding of this condition is improving rapidly. CASE 4 PRESENTATION A 30-year-old, right-handed woman is referred to a neurologist for further evaluation of chronic daily headache. Her headaches began at menarche, were nonlimiting, and were treated with butalbital. In college, her headaches increased in severity and frequency. Amitriptyline was helpful initially, but she then required a dose increase with only marginal benefit and a side effect of weight gain. The patient saw several headache specialists and multiple medications were tried. She also tried acupuncture and physical therapy. From ages 22 to 26 years, there was no specific prescribed treatment for headaches and the patient stopped seeing physicians altogether out of frustration. She started swimming with benefit, but she continued to take over-the-counter medications daily for headache. She reports that for a short time during a stress-free retail job she had no headache at all. At age 24 years, she started working in the family business and, with increased stress, noted increased headache. She re-entered care and resumed medication trials. The patient currently is taking sertraline (50 mg) and amitriptyline (30 mg) prophylactically. She uses sumatriptan (100 mg, 18 per month) and acetaminophen/ aspirin/caffeine (3 5 per day). She is waking daily with headache and says that she needs painkillers just to get to work by 11:00 am. She describes a bilateral periorbital severe, dull, steady ache that increases over the day, is worse on the right, increases with exposure to sunlight and with movement or cough, and decreases with relaxation. She also reports worsening headache during menses. In addition, she reports migraine superimposed on this daily pain, characterized as lateralized throbbing headache with photophobia and phonophobia. There is no associated nausea or vomiting. Concerned about the daily pattern of headaches but also alert to the patient s daily use of medication, the neurologist s initial diagnostic considerations are transformed migraine and medication overuse headache. How do the diagnoses of chronic daily headache, transformed migraine, and medication overuse headache interrelate? Although clinically important, chronic daily headache creates diagnostic difficulty. The ICHD-II classification system recognizes chronic migraine (usually without aura) and chronic tension-type headache. However, when also present in these patients, medication overuse headache takes precedence over these diagnoses. Medication overuse is probable until it can be determined that withdrawal of the agent improved the headache, at which time the probable may be dropped. This is a cumbersome system that fails to easily capture many of the patients in the clinic. By contrast, chronic daily headache is an inclusive term not found in the classification system that is used to refer to the entire group of chronic headaches: chronic migraine (previously transformed migraine), chronic tension-type headache, new daily persistent headache, and medication overuse headache. Chronic daily headache remains a clinically useful shorthand by which to describe these patients. The interrelationships among these chronic conditions have not been fully elucidated. Chronic daily headache, defined as more than 15 days of headache per month, has a consistent prevalence of about 4% in most population studied and is twice as common in females. 35 Most cases of chronic daily headache likely represent the transformation of migraine or tension-type headache from an episodic to a chronic pattern, as appears to be the case in this patient. Statistically, conditions seen in headache patients that may be associated with an increased risk of development of chronic daily headache include asthma, hypertension, hypothyroidism, allergy, and daily caffeine use. 36 Risk factors for incident chronic daily headache include frequent headache and migraine, female gender, changes in body mass index, the presence of diabetes or arthritis, and a history of traumatic life events. 37 Many patients with chronic daily headache are thought to be overusing medication, which is also illustrated in this case. Medications associated with probable Neurology Volume 10, Part 4 11

12 Table 8. Medications Associated with Probable Medication Overuse Headache Ergotamine intake on 10 or more days per month Triptan intake (any formulation) on 10 or more days per month Simple analgesic intake on 15 or more days per month Opioid intake on 10 or more days per month Use of combination analgesic medications on 10 or more days per month Intake of any combination of ergotamine, triptans, analgesics, and/or opioids on 10 or more days per month without overuse of any single class medication overuse headache are shown in Table 8. Medication overuse is thought to itself produce headache in susceptible individuals and may interfere with the efficacy of preventive medications in the treatment of headache. As most of these patients are using some sort of medication, however, medication overuse is almost always an issue in this group. CASE 4 CONTINUED The neurologist discusses a potentially helpful new therapy, botulinum toxin A. The patient agrees to try the treatment and receives the first set of injections. At follow-up 6 weeks later, the patient reports that she has had a partial response to the injections, but her overall medication use was the same and her headaches for the most part continued to be severe. Furthermore, she recently was involved in an accident with injury to her shoulder, and she has had shoulder and neck pain ever since. She says she has been getting regular aerobic exercise, doing posture exercises, and seeing a chiropractor and acupuncturist. The neurologist s clinical impression at this point is chronic daily headache and chronic cervical strain with associated trigger points. The neurologist feels that increased work stress and seasonal influences may be contributing to a worsening of the patient s condition. Topiramate and venlafaxine are added to her regimen, with benefit, although venlafaxine produces sexual side effects, forcing a dose reduction. The patient does not tolerate an increase in the topiramate, so the medication dose cannot be increased. At this point, she is still using 8 acetaminophen/aspirin/caffeine tablets daily and reports poor sleep habits. She receives another set of botulinum toxin injections. Is this patient s progress satisfactory to this point? Treatment of chronic daily headache is a game of inches, not miles. Polypharmacy is almost always needed, and the risk of medication interactions and side effects increases proportionately. Not all patients are as proactive with lifestyle modifications as this individual, but self-directed behavior plus continued employment likely improve the overall prognosis for patients with chronic daily headache. What is the current role of botulinum toxin in the treatment of headache? Botulinum toxin may have a role in headache management, 38 although its overall place has yet to be determined. Studies to date have not shown a robust response and are thought to suffer from methodological flaws. Also, the mechanism of action of the toxin in headache has yet to be elucidated. Anecdotally, however, botulinum toxin injections have shown some promise and are well tolerated in most patients, with a minimum of adverse effects and essentially no concern for medication interactions. The clinical effect may not be noted initially but instead may develop over the first 2 to 3 sets of injections (performed no sooner than every 3 months). An interesting observation is that most responders report that when the therapy wears off, the headaches return to their prior intensity almost immediately. Also, this pattern occurs predictably in an individual at the same time after each injection. Botulinum toxin therapy remains investigational and extremely expensive. CASE 4 CONTINUED At follow-up 2 months later, the patient s headaches are even more uncontrolled, prompting her to agree to once again increase the doses of venlafaxine and topiramate. At the next visit, her headaches have improved, and the work stress that was thought to be the greatest determinant of level of headache activity has decreased. The neurologist informs her that a reduction in her medications could be considered once it is determined that she has had a sustained benefit. The patient remains improved at the next visit, which is attributed to the higher medication doses and to reduced work stress. However, she continues to report a menstrual worsening of headache that is unresponsive to any therapy. It is difficult to determine if the botulinum toxin therapy has been helpful; by using functionality as a proxy for headache activity, the patient has been more active at work and able to travel, so the therapy is considered beneficial and is continued. At the next visit, the patient once again remains improved on amitriptyline, topiramate, venlafaxine, and botulinum toxin. She reports that her headaches improved when she was on vacation but they did not 12 Hospital Physician Board Review Manual

13 clear. After 6 more months of therapy, the patient is clearly better and able to work full-time reliably without missing multiple days. Is this outcome typical in patients with chronic daily headache? What is the prognosis for these patients? This patient s outcome thus far should probably be interpreted with a mixture of caution and optimism. Chronic daily headache has long been thought to have a relatively poor prognosis. As a complication of migraine, it is something we seek to prevent and why we adopt an aggressive stance in the management of episodic migraine. A significant number of spontaneous remissions in patients with chronic daily headache have recently been observed, boosting hope for improvement of a condition with a previously presumed poor prognosis. However, it is not yet clear when and if medications can be withdrawn after such improvement and whether further relapses are also part of the natural history of the illness in these patients. CLUSTER HEADACHE CASE 5 PRESENTATION A 56-year-old, left-handed man is referred to a headache clinic from a general neurologist for further evaluation of possible cluster headache. The patient denies childhood carsickness or abdominal pain but recalls headache onset in his teens in association with a positive family history of migraine. Headaches during his teen years were episodic, occurring for 1 to 2 months at a time every other night and then abating for about a year. The patient describes these headaches as left retro-orbital pains he treated with over-the-counter medications, application of a cold cloth, and rocking himself to sleep. Duration was about 1 hour. If he could sleep, he would wake without headache. Headaches are described as severe throbbing and aching, with pressure-like sensation. There was associated nausea and tearing of the left eye. This cluster pattern cleared in his late teens and then reappeared 5 to 7 years ago. Although initially more mild, the headache pattern is otherwise the same. Over time, however, the headaches have slowly increased in frequency and severity and have become associated with left-sided ptosis. Over the past 6 months, headaches have been occurring 3 times per day with a frequency of 3 days per week and duration of 1 to 2 hours. Onset is very rapid, intensity is severe, and an Table 9. ICHD-II Diagnostic Criteria for Cluster Headache A. At least 5 attacks fulfilling criteria B D B. Severe or very severe unilateral orbital, supraorbital and/or temporal pain lasting minutes if untreated C. Headache is accompanied by at least 1 of the following: 1. Ipsilateral conjunctival injection and/or lacrimation 2. Ipsilateral nasal congestion and/or rhinorrhea 3. Ipsilateral eyelid edema 4. Ipsilateral forehead and facial sweating 5. Ipsilateral miosis and/or ptosis 6. A sense of restlessness or agitation D. Attacks have a frequency from 1 every other day to 8 per day E. Not attributed to another disorder Reproduced by permission of Blackwell Science, Inc., from International Headache Society. International classification of headache disorders. 2nd edition. Cephalalgia 2004:24 Suppl 1:44. alcohol trigger is described. The patient has been using oxygen at home for treatment, which does shorten the duration of the headache. At times he also uses lidocaine nasal spray. He tried sumatriptan on one occasion without benefit. Short steroid courses have diminished but not aborted the headache. Verapamil (120 mg twice daily), used to treat hypertension, has not affected the headache. The patient does not smoke or use alcohol, the latter because it triggers his headache. Physical examination including vital signs is normal. Neurologic examination including detailed cranial nerve examination is also normal. Based on this history, what is the patient s diagnosis? This patient fits ICHD-II criteria for diagnosis of episodic cluster headache (Table 9). Cluster headache may be episodic or chronic. Episodic cluster, which represents 80% to 90% of cluster, is characterized by episodes of frequent (daily or greater) headaches interspersed with periods of remission, during which the patient is unable to get a headache. If 1 year passes without a remission, the pattern may be viewed as chronic cluster. Episodic cluster may evolve into a chronic pattern, or the chronic pattern may arise de novo. Based on the ICHD-II system, the case patient s headaches would not be considered chronic because the new pattern has been in place less than 1 year. CASE 5 CONTINUED A higher dose, longer course of steroids is given in an attempt to break the headache cycle. Propranolol Neurology Volume 10, Part 4 13

14 and topiramate are added to the verapamil for prevention, and zolmitriptan nasal spray is tried for acute symptoms, because of the history of lack of response to sumatriptan. Two weeks later, the patient reports improvement of his headaches but notes paresthesias in his fingers and mild confusion with word finding difficulty (recognized adverse events related to topirimate) as well as increased appetite and sleep disruption (side effects of prednisone treatment). The verapamil dose is increased, the prednisone is tapered, and topiramate is discontinued. What is the rationale for this approach? Verapamil is considered the drug of choice in the preventive treatment of both episodic and chronic cluster. 39 Higher doses are often needed, as much as 600 to 900 mg daily. At these doses, monitoring is required to avoid the complication of heart block. In this patient, however, combination therapy was attempted first in order to prevent the need for high doses of verapamil. Given the medication side effects as noted, it was decided to maximize the verapamil. Topirimate as used here is based only on anecdotal evidence. Other medications available in the United States for use in cluster headache prevention include lithium and corticosteroids. CASE 5 CONTINUED Two weeks later, the patient reports that the overall headache frequency has decreased but his headaches still occur daily. He reports another more nondescript daily headache as well. The verapamil is increased further, and the amount of zolmitriptan per month is also increased. Four weeks later, the patient has experienced only 9 headaches in the month, down from 3 nightly. Subsequently, headaches start to return and the verapamil is further increased. Three months later, the patient reports an increase in headache frequency and lithium is added. The patient is headache free for a short time on this combination of medications, but his headaches subsequently return. He is unable to tolerate the lithium side effects, and the medication is discontinued. The patient is then referred for evaluation for more invasive management. Is this history of concern, and is invasive management warranted? Cluster headache, although far less common than migraine, is not uncommon. Treatment of episodic cluster can be very rewarding. Unlike migraine, complete control of symptoms is sought, and in this way the management goals in cluster are more similar to those in trigeminal neuralgia. Management of chronic cluster is by contrast often very frustrating, and these are among the most difficult problems encountered in a headache clinic. Although many therapeutic options exist, including, for example, nerve blocks, getting control of this condition may be exceedingly difficult. More invasive measures, such as gamma knife, ablation procedures, or even deep brain stimulation are under investigation. The pattern illustrated by the history may suggest that the patient is transforming from an episodic to a chronic cluster pattern and is thus of concern. Aggressive management seems warranted to attempt to control symptoms and prevent progression. REFERENCES 1. Bigal ME, Lipton RB, Stewart WF. The epidemiology and impact of migraine. Curr Neurol Neurosci Rep 2004;4: Holmes WF, MacGregor EA, Dodick D. Migraine-related disability: impact and implications for sufferers lives and clinical issues. Neurology 2001;56(6 Suppl 1):S Lipton RB, Bigal ME. Migraine: epidemiology, impact and risk factors for progression. Headache 2005;45 Suppl 1:S3 S International Headache Society. International classification of headache disorders. 2nd edition. Cephalalgia 2004:24(Suppl 1): Nappi G, Granella F, Sandrini G, Manzoni GC. Chronic daily headache. How should it be included in the IHS classification? Headache 1999;39: Lichten EM, Lichten JB, Whitty A, Pieper D. The confirmation of a biochemical marker for women s hormonal migraine: the depo-oestradiol challenge test. Headache 1996;36: Lipton RB, Stewart WF, Diamond S, et al. Prevalence and burden of migraine in the United States: data from the American Migraine Study II. Headache 2001;41: Stewart WF, Lipton RB, Simon D. Work-related disability: results from the American migraine study. Cephalalgia 1996;16: Michel P, Dartigues JF, Lindousli A, Henry P. Loss of productivity and quality of life in migraine sufferers among French workers: results from the GAZEL cohort. Headache 1997;37: Swanson JW, Yanagihara T, Sang PE, et al. Incidence of cluster headaches: a population-based study in Olmsted County, Minnesota. Neurology 1994;44(3 Pt 1): D Alessandro R, Gamberini G, Benassi G, et al. Cluster headache in the Republic of San Marino. Cephalalgia 1986;6: Hospital Physician Board Review Manual

15 12. Schwartz BS, Stewart WF, Simon D, Lipton RB. Epidemiology of tension-type headache. JAMA 1998;279: Brandes JL. Headache diagnosis and testing. Proceedings of the 10th Congress of the International Headache Society; 2001 Jun 29; New York. 14. 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 [published erratum appears in Neurology 2000;56:142]. Neurology 2000;55: Spence JD, Amacher AL, Willis NR. Benign intracranial hypertension without papilledema: role of 24-hour cerebrospinal fluid pressure monitoring in diagnosis and management. Neurosurgery 1980;7: Mathew NT, Ravishankar K, Sanin LC. Coexistence of migraine and idiopathic intracranial hypertension without papilledema. Neurology 1996;46: Frishberg BM, Rosenberg JH, Matchar DB, et al. Evidencebased guidelines in the primary care setting: neuroimaging in patients with nonacute headache. American Academy of Neurology. Available at practice/index.cfm. Accessed 5 Oct Practice parameter: the electroencephalogram in the evaluation of headache (summary statement). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 1995;45: Ferrari MD, Roon KI, Lipton RB, Goadsby PJ. Oral triptans (serotonin 5-HT (1B/1D) agonists) in acute migraine treatment: a meta-analysis of 53 trials. Lancet 2001;358: Tepper SJ, Dahlof CG, Dowson A, et al. Prevalence and diagnosis of migraine in patients consulting their physician with a complaint of headache: data from the Landmark Study. Headache 2004;44: Loder E, Biondi D. General principles of migraine management: the changing role of prevention. Headache 2005;45 Suppl 1:S Olsson J-E, Behring HC, Forssman B, et al. Metoprolol and propranolol in migraine prophylaxis: a double-blind and multicentre study. Acta Neurol Scand 1984;70: Markley HG, Cheronis JC, Piepho RW. Verapamil prophylactic therapy of migraine. Neurology 1984;34: Tzourio C, Tehindrazanarivelo A, Iglesias S, et al. Casecontrol study of migraine and risk of ischaemic stroke in young women. BMJ 1995;310: Anzola GP, Magoni M, Guindani M, et al. Potential source of cerebral embolism in migraine with aura: a transcranial Doppler study. Neurology 1999;52: Milhaud D, Bogousslavsky J, van Melle G, Liot P. Ischemic stroke and active migraine. Neurology. 2001;57: Shapiro RE. Patent foramen ovale and migraine: why the flap? Headache 2006;46: Antonaci F, Ghirmai S, Bono G, et al. Cervicogenic headache: evaluation of the original diagnostic criteria. Cephalalgia 2001;21: Fernandez-de-las-Penas C, Alonso-Blanco C, Cuadrado ML, et al. Trigger points in the suboccipital muscles and forward head posture in tension-type headache. Headache 2006;46: Breslau N, Andreski P. Migraine, personality, and psychiatric comorbidity. Headache 1995;35: Bendtsen L, Jensen R, Olesen J. A non-selective (amitriptyline), but not a selective (citalopram) serotonin reuptake inhibitor is effective in the prophylactic treatment of chronic tension-type headache. J Neurol Neurosurg Psychiatry 1996;61: Carlsson J, Fahlcrantz A, Augustinsson LE. Muscle tenderness in tension headache treated with acupuncture or physiotherapy. Cephalalgia 1990;10: Triano JJ. Biomechanics of spinal manipulative therapy. Spine J 2001;1: Rains JC, Penzien DB, McCrory DC, Gray RN. Behavioral headache treatment: history, review of the empirical literature, and methodological critique. Headache 2005; 45 Suppl 2:S92 S Castillo J, Muñoz P, Guitera V, Pascual J. Epidemiology of chronic daily headache in the general population. Headache 1999;39: Bigal ME, Sheftell FD, Rapoport AM, et al. Chronic daily headache: identification of factors associated with induction and transformation. Headache 2002;42: 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: Wheeler AH. Botulinum toxin A, adjunctive therapy for refractory headaches associated with pericranial muscle tension. Headache 1998;38: Gabai IJ, Spierings EL. Prophylactic treatment of cluster headache with verapamil. Headache 1989;29: Copyright 2006 by Turner White Communications Inc., Wayne, PA. All rights reserved. Neurology Volume 10, Part 4 15

16 NOTES