Views and Perspectives

Views and Perspectives Clinical, Anatomical, and Physiologic Relationship Between Sleep and Headache David W. Dodick, MD; Eric J. Eross, MD; James M. Parish, MD The intimate relationship between sleep and headache has been recognized for centuries, yet the relationship remains clinically and nosologically complex. Headaches associated with nocturnal sleep have often been per- ceived as either the cause or result of disrupted sleep. An understanding of the anatomy and physiology of both conditions allows for a clearer understanding of this complex relationship and a more rational clinical and thera- peutic approach. Recent biochemical and functional imaging studies in patients with primary headache disorders has lead to the identification of potential central generators which are also important for the regulation of normal sleep architecture. Medical conditions (e.g. obstructive sleep apnea, depression) that may disrupt sleep and lead to nocturnal or morning headache can often be identified on clinical evaluation or by polysomnography. In contrast, primary headache disorders which often occur during nocturnal sleep or upon awakening, such as migraine, cluster headache, chronic paroxysmal hemicrania, and hypnic headache, can readily be diagnosed through clinical evaluation and managed with appropriate medication. These disorders, when not associated with co-morbid mood disorders or medications/analgesics overuse, seldom lead to significant sleep disruption. Identifying and classifying the specific headache disorder in patients with both headache and sleep disturbances can facilitate an appropriate diagnostic evaluation. Patients with poorly defined nocturnal or awakening headaches should undergo polysomnography to exclude a treatable sleep disturbance, especially in the absence of an underlying psychological disorder or analgesic overuse syndrome. In patients with a well defined primary headache disorder, unless there are compelling historical or examination findings suggestive of a primary sleep disturbance, a formal sleep evaluation is seldom necessary. Key words: headache, hypnic, hypothalamus, sleep, sleep apnea Abbreviations: CH cluster headache, CPH chronic paroxysmal hemicrania, OSA obstructive sleep apnea, PLMS period leg movements of sleep, REM rapid eye movement, NREM nonrapid eye movement, SCN suprachiasmatic nuclei (Headache 2003;43:282-292) That a relationship exists between sleep and matic. The great neurologic clinicians of the 19th and headaches has been known for more than a century, 20th centuries recognized that sleep deprivation and yet the exact nature of this association remains enig- excessive sleep were both associated with headache in general, and with migraine in particular, yet sleep itself has long been known as a powerful method to From the Department of Neurology (Drs. Dodick and Eross) and the Division of Pulmonary Medicine (Dr. Parish), Mayo terminate an attack. As early as 1853, Romberg Clinic, Scottsdale, Ariz. wrote that “The attack is generally closed by a pro- Printed in part for the American Academy of Neurology found and refreshing sleep” and Liveing remarked in Course Syllabus in 1999. 1873 that for an acute attack of migraine “The most 1,2 Address all correspondence to Dr. David W. Dodick, Depart- frequent termination by far is in sleep.” ment of Neurology, Mayo Clinic, 13400 East Shea Boulevard, In contrast, several well-described primary head- Scottsdale, AZ 85259. ache disorders, such as migraine, cluster headache Accepted for publication October 23, 2002. (CH), and chronic paroxysmal hemicrania (CPH), 282 Headache 283 may occur mainly during either nocturnal or diurnal Table 2.—Relationship Between Headache and Sleep* sleep. Moreover, hypnic headache syndrome appears to occur exclusively during sleep. These findings Headache is a symptom of a primary sleep disturbance suggest that the physiology of sleep itself may be re- Sleep disturbance is a symptom of a primary headache lated somehow to the mechanism underlying an disorder Sleep disturbance and heqadache are symptoms of an acute headache attack in a biologically predisposed unrelated medical disorder individual. Sleep disturbance and headache are both manifestations of a similar underlying pathogenesis CLASSIFICATION Controversy often implies two opposing and con- *Data from Paiva et al.3 tentious viewpoints, each of which is debated and dis- puted by those espousing the other side. However, controversy can also refer to an issue still open to mary sleep disturbance.3 In other words, the relation- question or under discussion. Such is the case with ship is one of “guilt by causation.” sleep and headache, especially because of the sparse Unfortunately, many studies analyzing the rela- research on the subject. The complex relationship be- tionship between sleep and headache have not ade- tween sleep and headache has led to various models quately defined their headache populations. First, the of potential interaction (Tables 1 and 2) that attempt headache populations are often described simply as to enhance our understanding of these disorders and “chronic” headache sufferers rather than being classi- ensure accurate diagnosis and management.3,4 fied into diagnostic categories. Second, the term Several investigators have concluded that “chronic chronic itself is not defined. Chronicity can be de- headache sufferers” often present with complex sleep fined either by the duration of a headache disorder disturbances that may be related to the headaches.5-7 (more than 6 months) or by the frequency of head- In addition, morning or nocturnal headaches have ache attacks (on more than 15 days per month). been found to be related often or frequently to a pri- These two parameters differ profoundly, particularly with respect to their potential effects on sleep. Fi- nally, little evidence is available on the frequency of Table 1.—Extent of Relationship Between comorbid illness (eg, depression, anxiety, medical Sleep and Headache* conditions) that may contribute to either the headaches, the sleep disturbance, or both. Sleep-related headaches (during or after sleep) In contrast, clearly defined primary headache Sleep-phase–related headaches III, IV, rapid eye movement: migraine disorders in isolation are rarely associated with major Rapid eye movement: cluster headache, chronic paroxysmal sleep disturbances, despite their occurrence predomi- hemicrania nantly or even exclusively during sleep.4 Further- Length of sleep and headaches Excessive deep sleep more, when specific sleep disorders are associated Lack of sleep with headaches, the headaches are often easily distin- Sleep disruption guished from the major headache syndromes and fre- Sleep relieves headaches Migraine and other types of headaches quently are accompanied by other features (eg, ex- Sleep disorders and headaches cessive daytime somnolence, cognitive impairment, Sleep apnea and headaches Somnambulism and headaches depression, anxiety) or by extensive sleep disruption. Other parasomnias and headaches Given the substantial clinical, anatomic, and bio- Effect of headaches on sleep logic overlap between the physiology of sleep and the Minimal to major sleep disruption Dreams and headaches pathophysiology of headache, their frequent association can be considered to be one of “guilt by associa- *Data from Sahota and Dexter.4 Reprinted with permission of tion.” However, their relationship might be defined the American Headache Society. more accurately by the following three paradigms: 284 March 2003 1. Headache is the result of disrupted noctur- In an earlier study of 288 consecutive patients at- nal sleep or the underlying process that dis- tending a headache clinic, Paiva and colleagues found rupts sleep. that 49 (17%) complained of nocturnal or early morn- a. Obstructive sleep apnea (OSA) or noc- ing headaches.7 Of this group, 26 (53%) were diag- turnal hypoxia or hypercarbia nosed with an identifiable sleep disorder, such as OSA, b. Restless legs syndrome or periodic leg PLMS, psychophysiologic insomnia, or fibromyalgia. movements of sleep (PLMS) Treatment directed toward the underlying sleep dis- c. Psychophysiologic insomnia order led to overall amelioration or improvement in d. Chronic pain syndrome or fibromyalgia the headaches of most patients, except in the group e. Depression or anxiety with PLMS. Although Paiva and colleagues con- 2. Headache is the “cause” of a disturbance cluded that headaches occurring during the night or of nocturnal sleep. early morning are often related to a sleep disturbance,7 a. Chronic tension-type headache (more they did not delineate the frequency or characteris- than 15 headache days per month for tics of headaches. more than 6 months) Still earlier, Paiva and colleagues had studied 25 b. Chronic migraine with or without anal- patients with nocturnal or early morning headaches,3 gesic abuse or depression or anxiety 21 of whom had subjective sleep complaints. Of these 3. Headache and sleep are intrinsically re- 21, 13 had a change in their headache diagnosis after lated by anatomy and physiology. overnight polysomnography,3 leading to final diag- a. Migraine noses that consisted of OSA, PLMS, fibromyalgia, or b. Cluster headache insomnia associated with chronic substance abuse. c. Chronic Paroxysmal Hemicrania These patients had presented with a variety of head- d. Hypnic headache ache diagnoses, including tension-type, “mixed tension-vascular,” and headaches caused by substance Headache as a Result of Sleep Disruption.—Head-

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