- Email: [email protected]
Sleep-Related Headaches
Sleep-Related Headaches Jeanetta C. Rains,
PhD
a,
*, J. Steven Poceta,
MD
b
KEYWORDS Sleep apnea headache Insomnia Migraine Cluster Hypnic headache Psychiatric comorbidity Treatment algorithm KEY POINTS Irrespective of diagnosis, chronic daily, morning, or “awakening” headache patterns are soft signs of a sleep disorder. Sleep apnea headache may emerge de novo or may present as an exacerbation of cluster, migraine, tension-type, or other headache. Insomnia is the most prevalent sleep disorder in chronic migraine and tension-type headache, and increases risk for depression and anxiety. Sleep disturbance (eg, sleep loss, oversleeping, schedule shift) is an acute headache trigger for migraine and tension-type headache. Snoring and sleep disturbance are independent risk factors for progression from episodic to chronic headache.
INTRODUCTION
Epidemiologic and clinical studies have associated sleep disorders with specific headache diagnoses (ie, migraine, tension-type, cluster, hypnic) and nonspecific headache patterns (ie, chronic daily, “awakening,” or morning headache). Irrespective of sleep disorders, acute sleep dysregulation is one of the most commonly reported headache triggers for episodic migraine and tension-type headache. Chronobiologic patterns have been identified in hypnic, cluster, and migraine headaches. Common neuroanatomic regulatory brain systems, mostly in the hypothalamus, help account for the interplay of sleep and headache. Headache has been associated with a wide range of respiratory and nonrespiratory sleep disorders.1,2 Most epidemiologic studies characterized headache according to frequency or proximity to sleep (ie, chronic daily, awakening, or morning headache) rather than formal diagnoses per the International Classification of Headache
Conflicts of interest: The authors have nothing to disclose. a Center for Sleep Evaluation, Elliot Hospital, 185 Queen City Avenue, Manchester, NH 03102, USA; b Division of Neurology, Sleep Center, Scripps Clinic, 10666 North Torrey Pines Road, La Jolla, CA 92037, USA * Corresponding author. E-mail address: [email protected] Neurol Clin 30 (2012) 1285–1298 http://dx.doi.org/10.1016/j.ncl.2012.08.014 neurologic.theclinics.com 0733-8619/12/$ – see front matter Ó 2012 Elsevier Inc. All rights reserved.
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Disorders, 2nd Edition (ICHD-II).3 Awakening headache has been most often studied and robustly linked to obstructive sleep apnea (OSA). The relative risk for chronic headache was shown to be increased at least 2- to 3-fold by sleep apnea; the odds ratio (OR) increased at least 8-fold in the case of cluster headache. Thus, although the average headache sufferer probably would not be diagnosed with OSA, patients with cluster and chronic headache not otherwise specified are 2 distinct subgroups at significant risk for OSA. Insomnia, circadian rhythm disorders, parasomnias, and daytime sleepiness were also shown to increase risk for chronic headache. Insomnia is the most common sleep disorder associated with migraine and tension-type headache. Insomnia (and to a lesser degree hypersomnia) is also a hallmark symptom of mood and anxiety disorders. Patients with migraine and chronic tension-type headache are 2- to 5-fold more likely than controls to experience depression or anxiety.4 Specifically, in migraineurs the lifetime incidence for major depression is 22% to 32% and for an anxiety disorder is 51% to 58%. Psychiatric comorbidity portends poorer long-term headache outcomes. Thus, the presence of insomnia in a patient experiencing chronic headaches warrants screening for psychiatric comorbidity. Notwithstanding sleep disorders, sleep loss and oversleeping are acute headache triggers. Stress, menstruation, and fasting are other common triggers. A literature review identified lack of sleep as a trigger in 48% to 74% of migraineurs (5 studies) and 26% to 72% of patients with tension-type headache (2 studies), and oversleeping as a trigger in 25% to 32% (3 studies) of migraineurs and 13% (1 study) of those with tension-type headache.5 The relationship between sleep duration and headache was confirmed prospectively in time series research by Houle and colleagues6 and found to be nonlinear, with the extreme ends of the sleep distribution (ie, short [<6 hours] and long sleep duration [>8.5 hours]) associated with increased headache intensity, whereas average sleep duration (7–8 hours) was associated with reduced headache. An interaction effect with stress was noted, suggesting sleep may be a moderating variable in the stress/headache relationship. EPIDEMIOLOGY AND RISK FACTORS
Chronic daily or awakening headache patterns have been shown to occur in 4% to 6% of the general population compared with 18% to 60% of obstructive sleep apneics and 18% of insomniacs.2 Epidemiologic research has shown that snorers and apneics exhibit headache, especially daily headache, more frequently than controls in crosssectional studies, with the relative risk increased at least 2- to 3-fold. Two specific subgroups seem to be at highest risk for OSA: patients with cluster and those with chronic headache patterns. A study of 37 patients with cluster headache who underwent polysomnography identified an 8.4-fold increase in the incidence of OSA relative to age- and gender-matched controls (58% vs 14%, respectively), and this risk increased more than 24-fold among patients with a body mass index (BMI) greater than 25 kg/m2.7 Likewise, Mitsikostas and colleagues8 identified OSA in 29% (21/ 72) of patients with severe headache who were refractory to standard treatments and were diagnosed with medication overuse and cluster and chronic tension-type headache. Insomnia occurs in half to two-thirds of migraineurs typically seen in neurology or specialty headache practices. In a cross-sectional study, Boardman and colleagues9 identified a dose–response relationship between headache and sleep (eg, trouble falling or staying asleep, feeling tired or worn out); among 2662 respondents, headache frequency increased with mild (age/gender-adjusted OR, 2.4 [1.7–3.2]), moderate (OR,
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3.6 [2.6–5.0]), and severe (OR, 7.5 [4.2–13.4]) sleep complaints. A relationship between insomnia and migraine persists after controlling for depression and anxiety.10 Circadian rhythm disorders and parasomnias (eg, nightmares, bruxism, sleepwalking) are at least 2-fold more frequent among individuals with daily headache compared with controls.11 Likewise, excessive daytime sleepiness seems to be increased in patients with migraine. A case-control study showed a 3-fold increase in pathologic daytime sleepiness based on questionnaires among migraineurs (14%) compared with controls (5%).12 DIFFERENTIAL DIAGNOSIS
Several diagnoses should be considered in cases of headache that emerge preferentially during or after sleep (Box 1). Sleep Apnea Headache
Sleep apnea headache is the only headache secondary to a sleep disorder recognized by the ICHD-II, coded under the major classification “headache attributed to disorder of homeostasis” and the subclassification of “headache attributed to hypoxia or hypercapnia.” Although OSA would account for most cases, diagnosis includes central sleep apnea, Cheyne-Stokes respiration, obesity hypoventilation syndrome, and mixed and complex sleep apnea syndromes. The diagnostic criteria and presumed mechanisms have yet to be validated and a sizable proportion of cases do not fulfill the criteria. Empirically, sleep apnea headache may present as migraine, tension, cluster, or unclassifiable; as bilateral (53%) or unilateral (47%); located frontal (33%), frontotemporal (28%), or temporal (16%); with pressing/tightening pain in most patients (79%); and with mild (47%), moderate (37%), or severe (16%) intensity.13 Headaches remit within 30 minutes of waking (criterion A.3) in only 40% of cases. Hypnic Headache
By definition, hypnic headache is confined to sleep and is known to occur in the mid to latter portion of the night, often between 1:00 and 3:00 AM, and less commonly during daytime naps. Because of the regularity of onset, it has been called “alarm clock” headache. Pain is usually mild to moderate, but may be severe.14 Hypnic headache is rare (only 174 cases were reported in the literature by 2011; <0.1% of specialty headache clinic cases). A meta-analysis of data pooled from 71 cases of hypnic headache published in the medical literature revealed an average duration of 67 44 minutes, a frequency of 1.2 0.9 per each 24 hours, and that 60% were bilateral and usually moderate in severity.15 Polysomnography has not isolated hypnic headache to a specific sleep stage, although anecdotal reports have suggested an association between hypnic headaches and OSA or rapid eye movement (REM)–related oxygen desaturations.14 Cluster Headache
Characterized by distinct circadian and, in some cases, circannual patterns, cluster headaches occur in series for weeks or months, separated by remissions of several months or years. Most headaches occur between 9:00 PM and 10:00 AM. OSA is prevalent among patients with cluster headache, especially those who are overweight and obese. Exploding Head Syndrome
Classified under parasomnias by the International Classification of Sleep Disorders, 2nd Edition [ICSD-2],16 criteria for exploding head syndrome include waking from
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Box 1 ICHD-II diagnostic criteria for sleep apnea, hypnic, and cluster headaches3
10.1.3 SLEEP APNEA HEADACHE A. Recurrent headache with at least one of the following characteristics and fulfilling criteria C and D: 1. Occurs on more than 15 days per month 2. Bilateral, pressing quality and not accompanied by nausea, photophobia, or phonophobia 3. Each headache resolves within 30 minutes B. Sleep apnea (respiratory disturbance index 5) shown on overnight polysomnography C. Headache is present on awakening D. Headache ceases within 72 hours and does not recur after effective treatment of sleep apnea
4.5 HYPNIC HEADACHE Attacks of dull headache that always awaken the patient from asleep. A. Dull headache fulfilling criteria B through D B. Develops only during sleep and awakens patient C. At least 2 of the following characteristics: 1. Occurs on more than 15 times per month 2. Lasts 15 minutes or longer after waking 3. First occurs after 50 years of age D. No autonomic symptoms and no more than one of nausea, photophobia, or phonophobia E. Not attributed to another disorder
3.1 CLUSTER HEADACHEa A. At least 5 attacks fulfilling criteria B through D B. Severe or very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15 to 180 minutes if untreated C. Headache is accompanied by at least one 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 a Cluster headache is subclassified as 3.1.1 episodic (at least 2 cluster periods lasting 7–365 days and separated by pain-free remission periods of 1 month) or 3.1.2 chronic (attacks recur over >1 year without remission periods or with remission periods lasting <1 month). Modified from Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders. 2nd edition. Cephalalgia 2004;24(Suppl 1):1–151; with permission.
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sleep or the wake–sleep transition with a sense of noise or explosion that is usually frightening to the patient and is notable for the absence of pain. The syndrome is not included in ICHD-II headache diagnoses because of the absence of pain, but the condition is often described among rare or short-lived headache disorders and may present to headache or sleep specialists. PATHOPHYSIOLOGY
Brennan and Charles17 recently described brain mechanisms that may underlie the relationship between sleep and headache. The central nervous system anatomy that generates sleep and alertness is centered in the monoaminergic and cholinergic nuclei in the basal forebrain and the brainstem interacting with the thalamus and the hypothalamus. The arousal-associated tuberomammillary nucleus, locus coeruleus, and dorsal and median raphe are inhibited by the ventrolateral preoptic nucleus of the hypothalamus viag-aminobutyric acid (GABA) and galanin. Adenosine, considered an endogenous somnogen, activates ventral lateral preoptic neurons in the hypothalamus, which induces sleep and is part of the homeostatic regulation of sleep and wake. In addition to the homeostatic drive for sleep and wake, a circadian mechanism exists to determine the likelihood of sleep at any point in the 24-hour day, and many headache syndromes also demonstrate circadian tendencies. The anatomy of headache and head pain is even more widespread, involving cervical inputs to the trigeminal nucleus caudalis, hypothalamus, periaqueductal gray (PAG) region, thalamus, cerebral cortex, cranial vessels. Several potential sites of interaction exist between the sleep and pain systems, notably in the hypothalamus and PAG. The ventrolateral portion of the PAG in particular, as mentioned by Brennan, is a region with both sleep and pain functions. Stimulation of this region of the PAG has affected motor behavior (quiescence) and the likelihood of REM sleep, and is also antinociceptive. The importance of the hypothalamus in the anatomic and physiologic underpinnings of migraine, cluster, and sleep mechanisms has been reviewed.1 The evidence for involvement of the hypothalamus in headache and sleep is suggested partly by the anatomy. For example, the hypothalamus is the site of the suprachiasmatic nucleus, the major circadian pacemaker in the brain; its nuclei contains hypocretin cells, in which loss of function is pathogenic in narcolepsy. Furthermore, the hypothalamus has extensive connections with the PAG matter, spinal nociceptive neurons, and the reticular system, and hence plays a regulatory role in pain and headache. Clinical aspects of the headache process also suggest involvement of the hypothalamus, such as the autonomic activation, yawning, and sleepiness associated with migraine. Direct imaging evidence shows hypothalamic activation in cluster headache and brainstem activation in migraine headache.18,19 A recent study assessed sleep using polysomnography in 3 patients with refractory chronic cluster headache before and after posterior hypothalamic deep brain stimulation.20 After deep brain stimulation, the expected improvement in headaches was associated with improved sleep efficiency and duration and decreased periodic limb movements in sleep. The timing of the circadian rhythm as measured by the temperature cycle was not altered. The clinical relationship between sleep and headache is defined by the fact that patients overwhelmingly identify sleep as a trigger for migraine. Several plausible mechanisms explain an effect of sleep on the likelihood of headache occurrence and its severity. For example, assessment of pain response in both humans and animals generally demonstrates a lower threshold after partial or complete sleep deprivation.21,22 The nature of this link and its underlying mechanisms are not clear.
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For example, REM sleep deprivation seems to have different effects from total sleep deprivation. Furthermore, one study suggested that sleep disruption is more likely to affect pain measures than is sleep restriction.23 In this study, groups of women were randomized to sleep overnight with either hourly interruptions or no interruptions. The interrupted group experienced increased spontaneous bodily pain and a significant loss of pain inhibition compared with the sleep-deprived (but continuous sleep) group. To the extent that headache pain is mediated by the same systems as bodily pain, which is not entirely clear because headache is a unique type of spontaneous pain syndrome, sleep duration and interruption seem to have the potential to alter the headache threshold. CLINICAL FEATURES AND DIAGNOSIS
Diagnosis begins with a thorough clinical interview, examining the headache history and patterns in relation to the sleep cycle. History may be supplemented by standardized questionnaires, a prospective diary, and objective monitoring. Headache History
A thorough headache history will obtain information on headache onset and course, chronology, pain characteristics, severity, frequency/duration/intensity, prodromes and auras, associated symptoms, precipitants, and past treatments,24 and will yield a specific ICHD-II diagnosis. Sleep History
Headache history may be examined in the context of a 24-hour sleep/wake cycle, considering presleep routine, sleep period (eg, sleep latency, duration of sleep relative to time in bed, mid-cycle and early morning awakenings), nocturnal symptoms (eg, respiratory, movement, waking), daytime functioning (eg, napping, alertness vs sleepiness, fatigue), and behavioral measures or substances to promote sleep or wakefulness. Useful information may be obtained from not only the patient but also the spouse or other observer. Patients who complain of insomnia should be questioned about internal and environmental contributors, such as (1) bedroom not conducive to sleep (eg, light, noise, television, cell phones, or other stimulation), (2) irregular sleep schedule, (3) napping or resting during the day, (4) medications and substances (eg, caffeine, alcohol, nicotine), and (5) emotional or cognitive arousal. Prediction Equations and Questionnaires
Risk for OSA,25 insomnia, and other sleep disorders may be assessed with validated tools. The most widely used tool for OSA is the Berlin Sleep Questionnaire, which yields a positive predictive value of 89%, and is based on neck circumference, habitual snoring or witnessed apnea, and hypertension.26 The STOP-Bang questionnaire was initially developed for screening presurgical patients for sleep apnea risk,27 but was more recently validated in the general medical population,28,29 and includes snoring, tiredness/sleepiness, observed apnea, blood pressure, BMI, age, neck circumference, and gender. Sleep Diary
A comprehensive diary for self-monitoring incidence of headache, sleep patterns, and other triggers of headache, such as stress, mood, and diet, is available elsewhere.30 Prospective sleep diaries are the most commonly used tool for diagnosing insomnia or circadian rhythm disorders and identifying headache triggers.
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Polysomnography
Attended polysomnography provides well-validated objective measures of sleep and wakefulness under standardized conditions, and normative data are available for a variety of sleep-disordered populations and normal controls. Typically, polysomnography is needed to confirm sleep-related breathing disorders, narcolepsy or idiopathic hypersomnia, and potentially injurious parasomnias. In uncomplicated cases in which a high pretest suspicion exists without confounding comorbidities, unattended and abbreviated portable monitoring may be sufficient to confirm OSA. TREATMENT
The following 6 recommendations follow the proposed headache management algorithm31 (Fig. 1) and the authors’ assessment of empiric evidence based on ICHD-II headache diagnoses and diagnosis-specific risk for sleep and psychiatric disorders. First, headache should be diagnosed according to standard criteria. Consider systematically diagnosing primary and secondary headaches according to ICHD-II criteria. Determine headache frequency (eg, chronic vs episodic). Second, a sleep history should be obtained. Consider headache symptoms in relation to the 24-hour sleep history; proximity to sleep (awakening headache); snoring; sleep schedule regularity; abnormal sleep duration (especially 6 hours or >8 hours); sleep hygiene; insomnia (difficulty initiating or maintaining or nonrestorative sleep); sleepiness; parasomnias and other perturbations of sleep (eg, restless legs, bruxism, nocturia); and daytime sequela, such as emotional and cognitive complaints. Third, sleep apnea headache should be ruled out in high-risk headache diagnoses. Patients diagnosed with cluster, hypnic, or any headache diagnosis that presents as chronic daily or awakening should be examined for symptoms and risk factors suggestive of sleep apnea (Box 2). Sleep apnea headache may represent an exacerbation of preexisting migraine or tension-type headache. STOP-Bang or other screening tools may prompt sleep specialist consultation or polysomnography. Confirmed OSA warrants treatment according to sleep medicine evidence-based guidelines32 using continuous positive airway pressure (CPAP), oral appliances, surgical intervention, or conservative management calibrated to symptoms. Conservative treatments alone are unlikely to be the preferred treatment for sleep apnea headache. Although headache would be expected to improve with treatment of sleep apnea, no basis exists to withhold headache treatment during the process of sleep evaluation or treatment. Concurrent headache treatment is usually indicated. Avoiding sedation with hypnotics or opiates is prudent until adherence to CPAP or other effective treatment for OSA is established. Treatment of headache that persists despite treatment of OSA depends on the exact headache diagnosis, but standard headache treatments apply for types such as migraine and cluster. Reevaluation of headache diagnosis and severity is recommended 1 month after sleep apnea treatment. After treatment is established, narcotic and sedative-hypnotics can be considered. Fourth, the presence of chronic headache and comorbid insomnia should be determined. Patients with chronic migraine and chronic tension-type headache are at particular risk for insomnia. Patients with chronic headache should be screened for insomnia, particularly those who are refractory to standard treatments (eg, receiving prophylaxis, experiencing withdrawal from medication overuse). Patients with
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Standard headache evaluation with 24-hour headache history
Determine ICHD-II headache diagnosis
Sleep Apnea Headache (suspect any frequent “awakening headache”)
Cluster Headache
Hypnic Headache
Chronic Migraine
Chronic Tension-Type (or frequent episodic)
Migraine +/- aura (episodic; <15/ days per month)
Tension-Type (episodic and infrequent)
Sleep history & screening tools
OSA, other sleep breathing disorder; narcolepsy or (primary) hypersomnia; parasomnia
Hypersomnia (secondary)
Insomnia
Circadian Rhythm
No sleep disorder or complaint
Psychiatric Disorder Diagnostic testing and/or sleep consult
Referral to specialist for Cognitive-behavior therapy
Behavioral sleep modification
Psychiatric consult and/or treatment
“Headache trigger” self-management
Fig. 1. Algorithm for management of sleep-related headache. (Adapted from Rains JC, Poceta JS. Sleep and headache. Curr Treat Options Neurol 2010;12:1–15; with permission.)
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Box 2 OSA: symptoms, risk factors, diagnosis, and treatment Clinical symptoms Habitual snoring Witnessed apnea Wake gasping or choking Morning headache Hypersomnia (or less often insomnia) Night sweats Nocturia Risk factors Overweight to obese (increased BMI, neck, chest, hips, and waist measurements) Male gender (less after menopause) Age (positive correlation) Family history Craniofacial morphology Oral anatomy (increased Mallampati score [Likert scale range, 1–4], tonsillar size [Likert scale range, 0–4]) Neuromuscular disorders Substance use (eg, tobacco, alcohol, sedatives) Screening procedures Questionnaires Prediction equations Screening overnight airflow, respiratory effort, and/or pulse oximetry Diagnostic testing Attended polysomnography Home or portable unattended cardiopulmonary monitoring Treatment options CPAP Surgery (eg, uvulopalatopharyngoplasty, tonsillectomy, tracheostomy, maxillomandibular surgery) Oral appliances (tongue retaining devices, mandibular advancement) Conservative measures Positional therapy to avoid supine sleep Weight loss Avoidance of alcohol, muscle relaxants, anxiolytics, sedatives, hypnotics, narcotics, and other medications that induce respiratory suppression
episodic migraine and tension-type headache may also benefit from screening for insomnia and other sleep disorders when their history suggests a significant sleep complaint or daytime sleepiness. Those with insomnia or poor sleep hygiene should be encouraged to undergo behavioral sleep regulation, which has been shown to
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significantly improve chronic migraine.33 The 5-component intervention used by Calhoun and Ford33 instructed patients to (1) schedule consistent bedtime that allows 8 hours in bed; (2) eliminate watching television, reading, or listening to music in bed; (3) use a visualization technique to shorten time to sleep onset; (4) move supper at least 4 hours before bedtime and limit fluids within 2 hours of bedtime; and (5) discontinue naps. Referral for more-intensive behavioral insomnia treatments may be needed. Although behavioral treatments are considered the preferred treatment for chronic insomnia, pharmacologic treatments may be indicated. No studies show that headache improves solely with pharmacologic treatment for insomnia, but pharmacologic treatment for insomnia may be warranted on a case-by-case basis. Benzodiazepines and nonbenzodiazepine hypnotics are effective, and some evidence shows that antidepressant medications are effective, although benefits must be weighed against potential adverse effects. No data are available to recommend a particular sleep aid for patients with headache among the available hypnotics, anxiolytics, or sedating antidepressants used to manage insomnia, but treatment should be tailored to symptom patterns. Choice of sedative-hypnotic, if used, depends on the nature of the insomnia, comorbid medical and psychiatric diagnoses, prior experience with hypnotics, substance abuse history, and pharmacokinetic properties of the drug (Tmax, half-life, side-effect profile, dependency risk). Drug choice also depends on whether the insomnia pattern involves sleep onset, maintenance (frequent awakenings at several time points in the night), or early morning awakening. Fifth, the presence of psychiatric comorbidities should be determined. Individuals with chronic migraine and tension-type headache are at risk for a psychiatric disorder, and screening for mood and anxiety disorders is warranted, especially when either insomnia or hypersomnia is present. Psychiatric symptoms impact choice of sedating versus alerting versus neutral pharmacologic agents.4 Sixth, sleep-related triggers of episodic headache should be identified. All patients with headache, and particularly those with episodic migraine and tension-type headache, may benefit from inclusion of sleep variables in trigger management. Prospective sleep diaries track the regularity, duration, and quality of sleep. The diary is the most commonly used systematic self-report tool for identifying headache triggers. Steps to manage headache triggers include 1. Prospective self-monitoring using the daily diary to record headache onset (or exacerbation in the case of chronic daily headache) along with common headache precipitants. Sleep variables of importance may be identified initially on interview but often may include daily monitoring of sleep schedule, quality and duration of sleep, daytime sleepiness, and napping. 2. Identifying triggers or events that result in a headache within 24 hours of exposure. Definite triggers cause headache 50% of time, possible triggers 25% to 50% of the time, and unlikely triggers less than 25% of the time. 3. Prioritizing triggers. Patients should be encouraged to address 2 or 3 of the most important triggers rather than undertake major lifestyle changes that often result in nonadherence. Ongoing self-monitoring allows patients to observe the outcome of behavior changes, which provides opportunities for refinement of strategies and reinforcement of self-management skills, and a sense of mastery and self-control of headache (self-efficacy). 4. Self-management skills. Patients may eliminate avoidable triggers, such as diet; modify their sleep environments (eg, light, noise); or predict and prepare for uncontrollable triggers (eg, menstrual).
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PROGNOSIS
Sleep regulation may improve headache. In the case of sleep apnea headache, headache improved or resolved in one-third to half of cases based on case series and uncontrolled studies,34–37 with few controlled trials.38 Few trials exist, and whether either hypnotics or behavioral insomnia therapies improve headache is unclear. However, a recent randomized controlled trial33 showed improvement in chronic migraine after a 12-week behavioral sleep intervention compared with a sham intervention; headache change was proportionate to the number of sleep behaviors changed (dose–response relationship). By the sixth week of treatment, 35% of the treatment group reverted from chronic to episodic headache compared with none of the controls. After treatment, the treatment group significantly improved over the control group in headache frequency (39% vs 12%) and index (28% vs –3%).
Case study: sleep apnea headache A 62-year-old man presented with daily headache that occurred “90% of the time” on awakening from the nocturnal sleep period and “25% to 50%” of the time when awakening from daytime naps. Pain was bilateral and temporal, throbbing, and moderate (5–6 on 10-point pain scale). No nausea or vomiting, aggravation with exertion, or phonophobia were experienced, but he did experience photophobia. Headache improved in 1 to 2 hours after waking with ibuprofen and/or acetaminophen and hydrocodone, or otherwise persisted “all morning” untreated. He had a history of cluster headache, treated prophylactically with verapamil. The most recent cluster phase was 6 months prior. Past medical history included asthma, hypertension, hyperlipidemia, gastroesophageal reflux, osteoarthritis, sinusitis, above-the-knee amputation for complications of methicillin-resistant Staphylococcus aureus after knee replacement in 2001 (without his prosthesis on motorized scooter). Medications included Symbicort, albuterol, furosemide, omeprazole, simvastatin, verapamil, isosorbide mononitrate, Losartan, and labetalol. His BMI was 42 kg/m2 (height, 69 in; weight, 285 lb); neck circumference was 20 in; and Mallampati score was 3 to 4. He wore dentures. His blood pressure was 150/84 mm Hg. He had no edema or clubbing and no focal neurologic deficits. He described his sleep history as “no trouble falling asleep, but my problem is staying asleep.” His presleep routine included dozing on the couch while watching television. He was in bed from 10:00 PM until 6:00 or 7:00 AM. His sleep latency was estimated at 2 minutes. His wife slept in a separate room because of his snoring. His family witnessed heroic snoring and apparent apneic events. His sleep was interrupted by nocturia 3 times per night, nightmares, sipping water for dry mouth, waking self from snoring, and pain awakenings. He denied worry or anticipation of poor sleep. He denied engaging in alerting activities in bed. He estimated sleeping only 3 to 4 hours net per night, although he was in bed 8 to 9 hours. He would awaken unrefreshed and would be dozing in the chair within 1 hour of waking. He napped ad-lib, falling to sleep during periods of inactivity, including while “holding my grandchild” and in social settings. He had a history of drowsy driving, which included a single-car, probably sleepiness-related motor vehicle accident 12 years ago at 4 PM while driving home from work. His score on the Epworth Sleepiness Scale was 17 (out of a maximum 24 possible), which was indicative of hypersomnia. His family history of sleep disorders included a son who was treated with CPAP for sleep apnea. Headache diagnoses included probable sleep apnea headache versus chronic tension-type headache versus medication overuse headache and history for episodic cluster headache. Polysomnography indicated OSA, he met all criteria on the STOP-Bang (1snoring, 1tiredness, 1observed apnea, 1hypertension, 1BMI, 1age, 1neck circumference >17 in, 1male gender), and he was diagnosed with nocturia. A split-night sleep study was conducted after OSA was diagnosed and deemed severe. During the initial approximately 3.5 hours of testing, the patient showed an apnea-hypopnea index of 65 events per hour, with oxygen desaturation to 66% and respiratory-related arousals. His CPAP was titrated to 14 cm H2O, with normalization of respiratory
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parameters in REM and non-REM sleep while supine. Sleep architecture included 5.3 hours net sleep, 71% of which occurred in bed, with 21% slow wave or stage 3 sleep and an extended REM cycle after CPAP, suggesting REM rebound. His arousal index was 38.3 and was mostly associated with pre-CPAP respiratory events. No periodic limb movements or other abnormalities were observed. He was prescribed CPAP at 14 cm H2O. At 30-day follow-up, his daily headaches were resolved and his subjective sleep and nocturia were improved. His objective CPAP adherence was 100% (30 of 30 days), with a mean daily use of 4 hours and 40 minutes per night. Daytime sleepiness was improved but not resolved, with a score on the Epworth Sleepiness Scale of 12 of 24. His treatment plan included long-term CPAP use, monitoring of mild persistent sleepiness, weight management, and determining whether treatment of apnea impacted cluster recurrence.
Current controversies and future considerations Sleep has been identified among risk factors for transformation from episodic to chronic headache in a sort of “disease progression” model. Lipton and Pan39 originally postulated that migraine might be conceptualized as a chronic progressive disorder. The progression or “chronification” of headache from episodic to “chronic daily headache” is a well-described clinical phenomenon, in which episodic migraine transforms to chronic daily headache over the span of months or years. Potential mechanisms for headache chronification have been described elsewhere,40 but progression is thought to be a consequence of the cortical spreading depression mechanisms that generate the migraine attacks; a function of the activations generated by the attacks, such as lesions in the periaqueductal gray area; and genetic and/or environmental risk factors. Snoring and sleep disturbance specifically were identified among risk factors for progression. Scher and colleagues41 found that patients with chronic daily headache were 3.3-fold more likely to be daily snorers than controls; the association was independent of headache type, gender, or age; and obesity was an independent risk factor for progression. These investigators and Wiendels and colleagues42 have also identified sleep disturbance as a significant risk factor for progression. Other risk factors included medication overuse, stress, psychiatric comorbidity, and obesity. Understanding the link between risk factors and headache may yield novel preventive and therapeutic approaches in the management of headache. Sleep and other modifiable risk factors may be potential targets for primary or secondary headache prevention rather than solely variables for management. Although yet untested in patients with headache, snoring interventions and sleep regulation strategies could be considered for prevention. The natural history of sleep-disordered breathing indicates a progression of simple snoring to OSA, influenced by aging and weight gain. Interventions aimed at weight loss, conservative measures for snoring, and basic sleep regulation warrant consideration. Longitudinal studies in the future would help determine if sleep regulation can reduce the risk of headache progression, but a fundamental shift from management to prevention could be realized currently.
REFERENCES
1. Poceta JS, Rains JC. Sleep and headache syndromes. Sleep Med Clin 2008;3(3): 427–41. 2. Rains JC, Poceta JS, Penzien DB. Sleep and headaches. Curr Neurol Neurosci Rep 2008;8:167–75. 3. Headache Classification Subcommittee of the International Headache Society. The international classification of headache disorders, second edition. Cephalalgia 2004;24(Suppl 1):1–151. 4. Smitherman TA, Maizels M, Penzien DB. Headache chronification: screening and behavioral management of comorbid depressive and anxiety disorders. Headache 2008;48:45–50.
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5. Martin PR, MacLeod C. Behavioral management of headache triggers: avoidance of triggers is an inadequate strategy. Clin Psychol Rev 2009;29:483–95. 6. Houle TT, Butschek RA, Turner DP. Stress and sleep predict headache severity in chronic headache sufferers. Pain, in press. 7. Nobre ME, Leal AJ, Filho PM. Investigation into sleep disturbance of patients suffering from cluster headache. Cephalalgia 2005;25(7):488–92. 8. Mitsikostas DD, Vikelis M, Viskos A. Refractory chronic headache associated with obstructive sleep apnoea syndrome. Cephalalgia 2007;28(2):139–43. 9. Boardman HF, Thomas E, Millson DS, et al. Psychological, sleep, lifestyle, and comorbid associations with headache. Headache 2005;45(6):657–69. 10. Vgontzas A, Lihong C, Merikangas KR. Are sleep difficulties associated with migraine attributable to anxiety and depression? Headache 2008;48(10):1451–9. 11. Ohayon MM. Prevalence and risk factors of morning headaches in the general population. Arch Intern Med 2004;164(1):97–102. 12. Barbanti P, Fabbrini G, Aurilia C, et al. A case-control study on excessive daytime sleepiness in episodic migraine. Cephalalgia 2007;27(10):1115–9. 13. Alberti A, Mazzotta G, Gallinella E, et al. Headache characteristics in obstructive sleep apnea and insomnia. Acta Neurol Scand 2005;111:309–16. 14. Holle D, Wessendorf TE, Zaremba S, et al. Serial polysomnography in hypnic headache. Cephalalgia 2011;31(3):286–90. 15. Evers S, Goadsby PJ. Hypnic headache: clinical features, pathophysiology, and treatment. Neurology 2003;60(6):905–9. 16. American Academy of Sleep Medicine. The International classification of sleep disorders. diagnostic and coding manual. 2nd edition. Westchester (IL): American Academy of Sleep Medicine; 2005. 17. Brennan KC, Charles A. Sleep and headaches. Semin Neurol 2009;29(4):406–18. 18. Aurora SK, Barrodale PM, Tipton RL, et al. Brainstem dysfunction in chronic migraine as evidenced by neurophysiological and positron emission tomography studies. Headache 2007;47(7):996–1003 [discussion: 1004–7]. 19. May A, Matharu M. New insights into migraine: application of functional and structural imaging. Curr Opin Neurol 2007;20(3):306–9. 20. Vetrugno R, Pierangeli G, Leone M, et al. Effect on sleep of posterior hypothalamus stimulation in cluster headache. Headache 2007;47(7):1085–90. 21. Wei H, Zhao W, Wang YX, et al. Pain-related behavior following REM sleep deprivation in the rat: influence of peripheral nerve injury, spinal glutamatergic receptors and nitric oxide. Brain Res 2007;1148:105–12. 22. Roehrs T, Hyde M, Blaisdell B, et al. Sleep loss and REM sleep loss are hyperalgesic. Sleep 2006;29(2):145–51. 23. Smith MT, Edwards RR, McCann UD, et al. The effects of sleep deprivation on pain inhibition and spontaneous pain in women. Sleep 2007;30(4):494–505. 24. Silberstein SD, Lipton RB, Dalessio DJ. Overview, diagnosis, and classification of headache. In: Silberstein SD, Lipton RB, Dodick DW, editors. Wolff’s headache and other head pain. 8th edition. Oxford University Press; 2007. 25. Abrishami A, Khajehdehi A, Chung F. A systematic review of screening questionnaires for obstructive sleep apnea. Can J Anaesth 2010;57(5):423–38. 26. Flemons WW, Whitelaw WA, Brant R, et al. Likelihood ratios for a sleep apnea clinical prediction rule. Am J Respir Crit Care Med 1994;150(5 Pt 1):1279–85. 27. Chung F, Yegneswaran B, Liao P, et al. STOP questionnaire: a tool to screen patients for obstructive sleep apnea. Anesthesiology 2008;108:812–21. 28. Ong TH, Raudha S, Fook-Chong S, et al. Simplifying STOP-Bang: use of a simple questionnaire to screen for OSA in an Asian population. Sleep Breath 2010;14:371–6.
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29. Silva GE, Vana KD, Goodwin JL, et al. Identification of patients with sleep disordered breathing: comparing the Four-Variable screening tool, STOP, STOP-Bang, and Epworth Sleepiness Scales. J Clin Sleep Med 2011;7(5):467–72. 30. Rains JC, Poceta JS. Headache and sleep disorders: review and clinical implications for headache management. Headache 2006;46(9):1344–61. 31. Rains JC, Poceta JS. Sleep and headache. Curr Treat Options Neurol 2010;12:1–15. 32. Morgenthaler TI, Kapen S, Lee-Chiong T, et al. Practice parameters for the medical therapy of obstructive sleep apnea. Sleep 2006;29(8):1031–5. 33. Calhoun AH, Ford S. Behavioral sleep modification may revert transformed migraine to episodic migraine. Headache 2007;47(8):1178–83. 34. Barloese M, Jennum P, Knudsen S, et al. Cluster headache and sleep, is there a connection? A review. Cephalalgia 2012;32(6):481–91. 35. Nath Zallek S, Chervin RD. Improvement in cluster headache after treatment for obstructive sleep apnea. Sleep Med 2000;1(2):135–8. 36. Paiva T, Farinha A, Martins A, et al. Chronic headaches and sleep disorders. Arch Intern Med 1997;157(15):1701–5. 37. Chervin RD, Zallek SN, Lin X, et al. Sleep disordered breathing in patients with cluster headache. Neurology 2000;54(12):2302–6. 38. Kiely JL, Murphy M, McNicholas WT. Subjective efficacy of nasal CPAP therapy in obstructive sleep apnoea syndrome: a prospective controlled study. Eur Respir J 1999;13(5):1086–90. 39. Lipton RB, Pan J. Is migraine a progressive disease? JAMA 2004;291(4):493–4. 40. Bigal M, Lipton RB. Concepts and mechanisms of migraine chronification. Headache 2008;48:7–15. 41. Scher AI, Lipton RB, Stewart WF. Habitual snoring as a risk factor for chronic daily headache. Neurology 2003;60(8):1366. 42. Wiendels NJ, Neven AK, Rosendaal FR, et al. Chronic frequent headache in the general population: prevalence and associated factors. Cephalalgia 2006; 26(12):1434–42.
PhD
a,
*, J. Steven Poceta,
MD
b
KEYWORDS Sleep apnea headache Insomnia Migraine Cluster Hypnic headache Psychiatric comorbidity Treatment algorithm KEY POINTS Irrespective of diagnosis, chronic daily, morning, or “awakening” headache patterns are soft signs of a sleep disorder. Sleep apnea headache may emerge de novo or may present as an exacerbation of cluster, migraine, tension-type, or other headache. Insomnia is the most prevalent sleep disorder in chronic migraine and tension-type headache, and increases risk for depression and anxiety. Sleep disturbance (eg, sleep loss, oversleeping, schedule shift) is an acute headache trigger for migraine and tension-type headache. Snoring and sleep disturbance are independent risk factors for progression from episodic to chronic headache.
INTRODUCTION
Epidemiologic and clinical studies have associated sleep disorders with specific headache diagnoses (ie, migraine, tension-type, cluster, hypnic) and nonspecific headache patterns (ie, chronic daily, “awakening,” or morning headache). Irrespective of sleep disorders, acute sleep dysregulation is one of the most commonly reported headache triggers for episodic migraine and tension-type headache. Chronobiologic patterns have been identified in hypnic, cluster, and migraine headaches. Common neuroanatomic regulatory brain systems, mostly in the hypothalamus, help account for the interplay of sleep and headache. Headache has been associated with a wide range of respiratory and nonrespiratory sleep disorders.1,2 Most epidemiologic studies characterized headache according to frequency or proximity to sleep (ie, chronic daily, awakening, or morning headache) rather than formal diagnoses per the International Classification of Headache
Conflicts of interest: The authors have nothing to disclose. a Center for Sleep Evaluation, Elliot Hospital, 185 Queen City Avenue, Manchester, NH 03102, USA; b Division of Neurology, Sleep Center, Scripps Clinic, 10666 North Torrey Pines Road, La Jolla, CA 92037, USA * Corresponding author. E-mail address: [email protected] Neurol Clin 30 (2012) 1285–1298 http://dx.doi.org/10.1016/j.ncl.2012.08.014 neurologic.theclinics.com 0733-8619/12/$ – see front matter Ó 2012 Elsevier Inc. All rights reserved.
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Disorders, 2nd Edition (ICHD-II).3 Awakening headache has been most often studied and robustly linked to obstructive sleep apnea (OSA). The relative risk for chronic headache was shown to be increased at least 2- to 3-fold by sleep apnea; the odds ratio (OR) increased at least 8-fold in the case of cluster headache. Thus, although the average headache sufferer probably would not be diagnosed with OSA, patients with cluster and chronic headache not otherwise specified are 2 distinct subgroups at significant risk for OSA. Insomnia, circadian rhythm disorders, parasomnias, and daytime sleepiness were also shown to increase risk for chronic headache. Insomnia is the most common sleep disorder associated with migraine and tension-type headache. Insomnia (and to a lesser degree hypersomnia) is also a hallmark symptom of mood and anxiety disorders. Patients with migraine and chronic tension-type headache are 2- to 5-fold more likely than controls to experience depression or anxiety.4 Specifically, in migraineurs the lifetime incidence for major depression is 22% to 32% and for an anxiety disorder is 51% to 58%. Psychiatric comorbidity portends poorer long-term headache outcomes. Thus, the presence of insomnia in a patient experiencing chronic headaches warrants screening for psychiatric comorbidity. Notwithstanding sleep disorders, sleep loss and oversleeping are acute headache triggers. Stress, menstruation, and fasting are other common triggers. A literature review identified lack of sleep as a trigger in 48% to 74% of migraineurs (5 studies) and 26% to 72% of patients with tension-type headache (2 studies), and oversleeping as a trigger in 25% to 32% (3 studies) of migraineurs and 13% (1 study) of those with tension-type headache.5 The relationship between sleep duration and headache was confirmed prospectively in time series research by Houle and colleagues6 and found to be nonlinear, with the extreme ends of the sleep distribution (ie, short [<6 hours] and long sleep duration [>8.5 hours]) associated with increased headache intensity, whereas average sleep duration (7–8 hours) was associated with reduced headache. An interaction effect with stress was noted, suggesting sleep may be a moderating variable in the stress/headache relationship. EPIDEMIOLOGY AND RISK FACTORS
Chronic daily or awakening headache patterns have been shown to occur in 4% to 6% of the general population compared with 18% to 60% of obstructive sleep apneics and 18% of insomniacs.2 Epidemiologic research has shown that snorers and apneics exhibit headache, especially daily headache, more frequently than controls in crosssectional studies, with the relative risk increased at least 2- to 3-fold. Two specific subgroups seem to be at highest risk for OSA: patients with cluster and those with chronic headache patterns. A study of 37 patients with cluster headache who underwent polysomnography identified an 8.4-fold increase in the incidence of OSA relative to age- and gender-matched controls (58% vs 14%, respectively), and this risk increased more than 24-fold among patients with a body mass index (BMI) greater than 25 kg/m2.7 Likewise, Mitsikostas and colleagues8 identified OSA in 29% (21/ 72) of patients with severe headache who were refractory to standard treatments and were diagnosed with medication overuse and cluster and chronic tension-type headache. Insomnia occurs in half to two-thirds of migraineurs typically seen in neurology or specialty headache practices. In a cross-sectional study, Boardman and colleagues9 identified a dose–response relationship between headache and sleep (eg, trouble falling or staying asleep, feeling tired or worn out); among 2662 respondents, headache frequency increased with mild (age/gender-adjusted OR, 2.4 [1.7–3.2]), moderate (OR,
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3.6 [2.6–5.0]), and severe (OR, 7.5 [4.2–13.4]) sleep complaints. A relationship between insomnia and migraine persists after controlling for depression and anxiety.10 Circadian rhythm disorders and parasomnias (eg, nightmares, bruxism, sleepwalking) are at least 2-fold more frequent among individuals with daily headache compared with controls.11 Likewise, excessive daytime sleepiness seems to be increased in patients with migraine. A case-control study showed a 3-fold increase in pathologic daytime sleepiness based on questionnaires among migraineurs (14%) compared with controls (5%).12 DIFFERENTIAL DIAGNOSIS
Several diagnoses should be considered in cases of headache that emerge preferentially during or after sleep (Box 1). Sleep Apnea Headache
Sleep apnea headache is the only headache secondary to a sleep disorder recognized by the ICHD-II, coded under the major classification “headache attributed to disorder of homeostasis” and the subclassification of “headache attributed to hypoxia or hypercapnia.” Although OSA would account for most cases, diagnosis includes central sleep apnea, Cheyne-Stokes respiration, obesity hypoventilation syndrome, and mixed and complex sleep apnea syndromes. The diagnostic criteria and presumed mechanisms have yet to be validated and a sizable proportion of cases do not fulfill the criteria. Empirically, sleep apnea headache may present as migraine, tension, cluster, or unclassifiable; as bilateral (53%) or unilateral (47%); located frontal (33%), frontotemporal (28%), or temporal (16%); with pressing/tightening pain in most patients (79%); and with mild (47%), moderate (37%), or severe (16%) intensity.13 Headaches remit within 30 minutes of waking (criterion A.3) in only 40% of cases. Hypnic Headache
By definition, hypnic headache is confined to sleep and is known to occur in the mid to latter portion of the night, often between 1:00 and 3:00 AM, and less commonly during daytime naps. Because of the regularity of onset, it has been called “alarm clock” headache. Pain is usually mild to moderate, but may be severe.14 Hypnic headache is rare (only 174 cases were reported in the literature by 2011; <0.1% of specialty headache clinic cases). A meta-analysis of data pooled from 71 cases of hypnic headache published in the medical literature revealed an average duration of 67 44 minutes, a frequency of 1.2 0.9 per each 24 hours, and that 60% were bilateral and usually moderate in severity.15 Polysomnography has not isolated hypnic headache to a specific sleep stage, although anecdotal reports have suggested an association between hypnic headaches and OSA or rapid eye movement (REM)–related oxygen desaturations.14 Cluster Headache
Characterized by distinct circadian and, in some cases, circannual patterns, cluster headaches occur in series for weeks or months, separated by remissions of several months or years. Most headaches occur between 9:00 PM and 10:00 AM. OSA is prevalent among patients with cluster headache, especially those who are overweight and obese. Exploding Head Syndrome
Classified under parasomnias by the International Classification of Sleep Disorders, 2nd Edition [ICSD-2],16 criteria for exploding head syndrome include waking from
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Box 1 ICHD-II diagnostic criteria for sleep apnea, hypnic, and cluster headaches3
10.1.3 SLEEP APNEA HEADACHE A. Recurrent headache with at least one of the following characteristics and fulfilling criteria C and D: 1. Occurs on more than 15 days per month 2. Bilateral, pressing quality and not accompanied by nausea, photophobia, or phonophobia 3. Each headache resolves within 30 minutes B. Sleep apnea (respiratory disturbance index 5) shown on overnight polysomnography C. Headache is present on awakening D. Headache ceases within 72 hours and does not recur after effective treatment of sleep apnea
4.5 HYPNIC HEADACHE Attacks of dull headache that always awaken the patient from asleep. A. Dull headache fulfilling criteria B through D B. Develops only during sleep and awakens patient C. At least 2 of the following characteristics: 1. Occurs on more than 15 times per month 2. Lasts 15 minutes or longer after waking 3. First occurs after 50 years of age D. No autonomic symptoms and no more than one of nausea, photophobia, or phonophobia E. Not attributed to another disorder
3.1 CLUSTER HEADACHEa A. At least 5 attacks fulfilling criteria B through D B. Severe or very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15 to 180 minutes if untreated C. Headache is accompanied by at least one 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 a Cluster headache is subclassified as 3.1.1 episodic (at least 2 cluster periods lasting 7–365 days and separated by pain-free remission periods of 1 month) or 3.1.2 chronic (attacks recur over >1 year without remission periods or with remission periods lasting <1 month). Modified from Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders. 2nd edition. Cephalalgia 2004;24(Suppl 1):1–151; with permission.
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sleep or the wake–sleep transition with a sense of noise or explosion that is usually frightening to the patient and is notable for the absence of pain. The syndrome is not included in ICHD-II headache diagnoses because of the absence of pain, but the condition is often described among rare or short-lived headache disorders and may present to headache or sleep specialists. PATHOPHYSIOLOGY
Brennan and Charles17 recently described brain mechanisms that may underlie the relationship between sleep and headache. The central nervous system anatomy that generates sleep and alertness is centered in the monoaminergic and cholinergic nuclei in the basal forebrain and the brainstem interacting with the thalamus and the hypothalamus. The arousal-associated tuberomammillary nucleus, locus coeruleus, and dorsal and median raphe are inhibited by the ventrolateral preoptic nucleus of the hypothalamus viag-aminobutyric acid (GABA) and galanin. Adenosine, considered an endogenous somnogen, activates ventral lateral preoptic neurons in the hypothalamus, which induces sleep and is part of the homeostatic regulation of sleep and wake. In addition to the homeostatic drive for sleep and wake, a circadian mechanism exists to determine the likelihood of sleep at any point in the 24-hour day, and many headache syndromes also demonstrate circadian tendencies. The anatomy of headache and head pain is even more widespread, involving cervical inputs to the trigeminal nucleus caudalis, hypothalamus, periaqueductal gray (PAG) region, thalamus, cerebral cortex, cranial vessels. Several potential sites of interaction exist between the sleep and pain systems, notably in the hypothalamus and PAG. The ventrolateral portion of the PAG in particular, as mentioned by Brennan, is a region with both sleep and pain functions. Stimulation of this region of the PAG has affected motor behavior (quiescence) and the likelihood of REM sleep, and is also antinociceptive. The importance of the hypothalamus in the anatomic and physiologic underpinnings of migraine, cluster, and sleep mechanisms has been reviewed.1 The evidence for involvement of the hypothalamus in headache and sleep is suggested partly by the anatomy. For example, the hypothalamus is the site of the suprachiasmatic nucleus, the major circadian pacemaker in the brain; its nuclei contains hypocretin cells, in which loss of function is pathogenic in narcolepsy. Furthermore, the hypothalamus has extensive connections with the PAG matter, spinal nociceptive neurons, and the reticular system, and hence plays a regulatory role in pain and headache. Clinical aspects of the headache process also suggest involvement of the hypothalamus, such as the autonomic activation, yawning, and sleepiness associated with migraine. Direct imaging evidence shows hypothalamic activation in cluster headache and brainstem activation in migraine headache.18,19 A recent study assessed sleep using polysomnography in 3 patients with refractory chronic cluster headache before and after posterior hypothalamic deep brain stimulation.20 After deep brain stimulation, the expected improvement in headaches was associated with improved sleep efficiency and duration and decreased periodic limb movements in sleep. The timing of the circadian rhythm as measured by the temperature cycle was not altered. The clinical relationship between sleep and headache is defined by the fact that patients overwhelmingly identify sleep as a trigger for migraine. Several plausible mechanisms explain an effect of sleep on the likelihood of headache occurrence and its severity. For example, assessment of pain response in both humans and animals generally demonstrates a lower threshold after partial or complete sleep deprivation.21,22 The nature of this link and its underlying mechanisms are not clear.
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For example, REM sleep deprivation seems to have different effects from total sleep deprivation. Furthermore, one study suggested that sleep disruption is more likely to affect pain measures than is sleep restriction.23 In this study, groups of women were randomized to sleep overnight with either hourly interruptions or no interruptions. The interrupted group experienced increased spontaneous bodily pain and a significant loss of pain inhibition compared with the sleep-deprived (but continuous sleep) group. To the extent that headache pain is mediated by the same systems as bodily pain, which is not entirely clear because headache is a unique type of spontaneous pain syndrome, sleep duration and interruption seem to have the potential to alter the headache threshold. CLINICAL FEATURES AND DIAGNOSIS
Diagnosis begins with a thorough clinical interview, examining the headache history and patterns in relation to the sleep cycle. History may be supplemented by standardized questionnaires, a prospective diary, and objective monitoring. Headache History
A thorough headache history will obtain information on headache onset and course, chronology, pain characteristics, severity, frequency/duration/intensity, prodromes and auras, associated symptoms, precipitants, and past treatments,24 and will yield a specific ICHD-II diagnosis. Sleep History
Headache history may be examined in the context of a 24-hour sleep/wake cycle, considering presleep routine, sleep period (eg, sleep latency, duration of sleep relative to time in bed, mid-cycle and early morning awakenings), nocturnal symptoms (eg, respiratory, movement, waking), daytime functioning (eg, napping, alertness vs sleepiness, fatigue), and behavioral measures or substances to promote sleep or wakefulness. Useful information may be obtained from not only the patient but also the spouse or other observer. Patients who complain of insomnia should be questioned about internal and environmental contributors, such as (1) bedroom not conducive to sleep (eg, light, noise, television, cell phones, or other stimulation), (2) irregular sleep schedule, (3) napping or resting during the day, (4) medications and substances (eg, caffeine, alcohol, nicotine), and (5) emotional or cognitive arousal. Prediction Equations and Questionnaires
Risk for OSA,25 insomnia, and other sleep disorders may be assessed with validated tools. The most widely used tool for OSA is the Berlin Sleep Questionnaire, which yields a positive predictive value of 89%, and is based on neck circumference, habitual snoring or witnessed apnea, and hypertension.26 The STOP-Bang questionnaire was initially developed for screening presurgical patients for sleep apnea risk,27 but was more recently validated in the general medical population,28,29 and includes snoring, tiredness/sleepiness, observed apnea, blood pressure, BMI, age, neck circumference, and gender. Sleep Diary
A comprehensive diary for self-monitoring incidence of headache, sleep patterns, and other triggers of headache, such as stress, mood, and diet, is available elsewhere.30 Prospective sleep diaries are the most commonly used tool for diagnosing insomnia or circadian rhythm disorders and identifying headache triggers.
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Polysomnography
Attended polysomnography provides well-validated objective measures of sleep and wakefulness under standardized conditions, and normative data are available for a variety of sleep-disordered populations and normal controls. Typically, polysomnography is needed to confirm sleep-related breathing disorders, narcolepsy or idiopathic hypersomnia, and potentially injurious parasomnias. In uncomplicated cases in which a high pretest suspicion exists without confounding comorbidities, unattended and abbreviated portable monitoring may be sufficient to confirm OSA. TREATMENT
The following 6 recommendations follow the proposed headache management algorithm31 (Fig. 1) and the authors’ assessment of empiric evidence based on ICHD-II headache diagnoses and diagnosis-specific risk for sleep and psychiatric disorders. First, headache should be diagnosed according to standard criteria. Consider systematically diagnosing primary and secondary headaches according to ICHD-II criteria. Determine headache frequency (eg, chronic vs episodic). Second, a sleep history should be obtained. Consider headache symptoms in relation to the 24-hour sleep history; proximity to sleep (awakening headache); snoring; sleep schedule regularity; abnormal sleep duration (especially 6 hours or >8 hours); sleep hygiene; insomnia (difficulty initiating or maintaining or nonrestorative sleep); sleepiness; parasomnias and other perturbations of sleep (eg, restless legs, bruxism, nocturia); and daytime sequela, such as emotional and cognitive complaints. Third, sleep apnea headache should be ruled out in high-risk headache diagnoses. Patients diagnosed with cluster, hypnic, or any headache diagnosis that presents as chronic daily or awakening should be examined for symptoms and risk factors suggestive of sleep apnea (Box 2). Sleep apnea headache may represent an exacerbation of preexisting migraine or tension-type headache. STOP-Bang or other screening tools may prompt sleep specialist consultation or polysomnography. Confirmed OSA warrants treatment according to sleep medicine evidence-based guidelines32 using continuous positive airway pressure (CPAP), oral appliances, surgical intervention, or conservative management calibrated to symptoms. Conservative treatments alone are unlikely to be the preferred treatment for sleep apnea headache. Although headache would be expected to improve with treatment of sleep apnea, no basis exists to withhold headache treatment during the process of sleep evaluation or treatment. Concurrent headache treatment is usually indicated. Avoiding sedation with hypnotics or opiates is prudent until adherence to CPAP or other effective treatment for OSA is established. Treatment of headache that persists despite treatment of OSA depends on the exact headache diagnosis, but standard headache treatments apply for types such as migraine and cluster. Reevaluation of headache diagnosis and severity is recommended 1 month after sleep apnea treatment. After treatment is established, narcotic and sedative-hypnotics can be considered. Fourth, the presence of chronic headache and comorbid insomnia should be determined. Patients with chronic migraine and chronic tension-type headache are at particular risk for insomnia. Patients with chronic headache should be screened for insomnia, particularly those who are refractory to standard treatments (eg, receiving prophylaxis, experiencing withdrawal from medication overuse). Patients with
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Standard headache evaluation with 24-hour headache history
Determine ICHD-II headache diagnosis
Sleep Apnea Headache (suspect any frequent “awakening headache”)
Cluster Headache
Hypnic Headache
Chronic Migraine
Chronic Tension-Type (or frequent episodic)
Migraine +/- aura (episodic; <15/ days per month)
Tension-Type (episodic and infrequent)
Sleep history & screening tools
OSA, other sleep breathing disorder; narcolepsy or (primary) hypersomnia; parasomnia
Hypersomnia (secondary)
Insomnia
Circadian Rhythm
No sleep disorder or complaint
Psychiatric Disorder Diagnostic testing and/or sleep consult
Referral to specialist for Cognitive-behavior therapy
Behavioral sleep modification
Psychiatric consult and/or treatment
“Headache trigger” self-management
Fig. 1. Algorithm for management of sleep-related headache. (Adapted from Rains JC, Poceta JS. Sleep and headache. Curr Treat Options Neurol 2010;12:1–15; with permission.)
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Box 2 OSA: symptoms, risk factors, diagnosis, and treatment Clinical symptoms Habitual snoring Witnessed apnea Wake gasping or choking Morning headache Hypersomnia (or less often insomnia) Night sweats Nocturia Risk factors Overweight to obese (increased BMI, neck, chest, hips, and waist measurements) Male gender (less after menopause) Age (positive correlation) Family history Craniofacial morphology Oral anatomy (increased Mallampati score [Likert scale range, 1–4], tonsillar size [Likert scale range, 0–4]) Neuromuscular disorders Substance use (eg, tobacco, alcohol, sedatives) Screening procedures Questionnaires Prediction equations Screening overnight airflow, respiratory effort, and/or pulse oximetry Diagnostic testing Attended polysomnography Home or portable unattended cardiopulmonary monitoring Treatment options CPAP Surgery (eg, uvulopalatopharyngoplasty, tonsillectomy, tracheostomy, maxillomandibular surgery) Oral appliances (tongue retaining devices, mandibular advancement) Conservative measures Positional therapy to avoid supine sleep Weight loss Avoidance of alcohol, muscle relaxants, anxiolytics, sedatives, hypnotics, narcotics, and other medications that induce respiratory suppression
episodic migraine and tension-type headache may also benefit from screening for insomnia and other sleep disorders when their history suggests a significant sleep complaint or daytime sleepiness. Those with insomnia or poor sleep hygiene should be encouraged to undergo behavioral sleep regulation, which has been shown to
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significantly improve chronic migraine.33 The 5-component intervention used by Calhoun and Ford33 instructed patients to (1) schedule consistent bedtime that allows 8 hours in bed; (2) eliminate watching television, reading, or listening to music in bed; (3) use a visualization technique to shorten time to sleep onset; (4) move supper at least 4 hours before bedtime and limit fluids within 2 hours of bedtime; and (5) discontinue naps. Referral for more-intensive behavioral insomnia treatments may be needed. Although behavioral treatments are considered the preferred treatment for chronic insomnia, pharmacologic treatments may be indicated. No studies show that headache improves solely with pharmacologic treatment for insomnia, but pharmacologic treatment for insomnia may be warranted on a case-by-case basis. Benzodiazepines and nonbenzodiazepine hypnotics are effective, and some evidence shows that antidepressant medications are effective, although benefits must be weighed against potential adverse effects. No data are available to recommend a particular sleep aid for patients with headache among the available hypnotics, anxiolytics, or sedating antidepressants used to manage insomnia, but treatment should be tailored to symptom patterns. Choice of sedative-hypnotic, if used, depends on the nature of the insomnia, comorbid medical and psychiatric diagnoses, prior experience with hypnotics, substance abuse history, and pharmacokinetic properties of the drug (Tmax, half-life, side-effect profile, dependency risk). Drug choice also depends on whether the insomnia pattern involves sleep onset, maintenance (frequent awakenings at several time points in the night), or early morning awakening. Fifth, the presence of psychiatric comorbidities should be determined. Individuals with chronic migraine and tension-type headache are at risk for a psychiatric disorder, and screening for mood and anxiety disorders is warranted, especially when either insomnia or hypersomnia is present. Psychiatric symptoms impact choice of sedating versus alerting versus neutral pharmacologic agents.4 Sixth, sleep-related triggers of episodic headache should be identified. All patients with headache, and particularly those with episodic migraine and tension-type headache, may benefit from inclusion of sleep variables in trigger management. Prospective sleep diaries track the regularity, duration, and quality of sleep. The diary is the most commonly used systematic self-report tool for identifying headache triggers. Steps to manage headache triggers include 1. Prospective self-monitoring using the daily diary to record headache onset (or exacerbation in the case of chronic daily headache) along with common headache precipitants. Sleep variables of importance may be identified initially on interview but often may include daily monitoring of sleep schedule, quality and duration of sleep, daytime sleepiness, and napping. 2. Identifying triggers or events that result in a headache within 24 hours of exposure. Definite triggers cause headache 50% of time, possible triggers 25% to 50% of the time, and unlikely triggers less than 25% of the time. 3. Prioritizing triggers. Patients should be encouraged to address 2 or 3 of the most important triggers rather than undertake major lifestyle changes that often result in nonadherence. Ongoing self-monitoring allows patients to observe the outcome of behavior changes, which provides opportunities for refinement of strategies and reinforcement of self-management skills, and a sense of mastery and self-control of headache (self-efficacy). 4. Self-management skills. Patients may eliminate avoidable triggers, such as diet; modify their sleep environments (eg, light, noise); or predict and prepare for uncontrollable triggers (eg, menstrual).
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PROGNOSIS
Sleep regulation may improve headache. In the case of sleep apnea headache, headache improved or resolved in one-third to half of cases based on case series and uncontrolled studies,34–37 with few controlled trials.38 Few trials exist, and whether either hypnotics or behavioral insomnia therapies improve headache is unclear. However, a recent randomized controlled trial33 showed improvement in chronic migraine after a 12-week behavioral sleep intervention compared with a sham intervention; headache change was proportionate to the number of sleep behaviors changed (dose–response relationship). By the sixth week of treatment, 35% of the treatment group reverted from chronic to episodic headache compared with none of the controls. After treatment, the treatment group significantly improved over the control group in headache frequency (39% vs 12%) and index (28% vs –3%).
Case study: sleep apnea headache A 62-year-old man presented with daily headache that occurred “90% of the time” on awakening from the nocturnal sleep period and “25% to 50%” of the time when awakening from daytime naps. Pain was bilateral and temporal, throbbing, and moderate (5–6 on 10-point pain scale). No nausea or vomiting, aggravation with exertion, or phonophobia were experienced, but he did experience photophobia. Headache improved in 1 to 2 hours after waking with ibuprofen and/or acetaminophen and hydrocodone, or otherwise persisted “all morning” untreated. He had a history of cluster headache, treated prophylactically with verapamil. The most recent cluster phase was 6 months prior. Past medical history included asthma, hypertension, hyperlipidemia, gastroesophageal reflux, osteoarthritis, sinusitis, above-the-knee amputation for complications of methicillin-resistant Staphylococcus aureus after knee replacement in 2001 (without his prosthesis on motorized scooter). Medications included Symbicort, albuterol, furosemide, omeprazole, simvastatin, verapamil, isosorbide mononitrate, Losartan, and labetalol. His BMI was 42 kg/m2 (height, 69 in; weight, 285 lb); neck circumference was 20 in; and Mallampati score was 3 to 4. He wore dentures. His blood pressure was 150/84 mm Hg. He had no edema or clubbing and no focal neurologic deficits. He described his sleep history as “no trouble falling asleep, but my problem is staying asleep.” His presleep routine included dozing on the couch while watching television. He was in bed from 10:00 PM until 6:00 or 7:00 AM. His sleep latency was estimated at 2 minutes. His wife slept in a separate room because of his snoring. His family witnessed heroic snoring and apparent apneic events. His sleep was interrupted by nocturia 3 times per night, nightmares, sipping water for dry mouth, waking self from snoring, and pain awakenings. He denied worry or anticipation of poor sleep. He denied engaging in alerting activities in bed. He estimated sleeping only 3 to 4 hours net per night, although he was in bed 8 to 9 hours. He would awaken unrefreshed and would be dozing in the chair within 1 hour of waking. He napped ad-lib, falling to sleep during periods of inactivity, including while “holding my grandchild” and in social settings. He had a history of drowsy driving, which included a single-car, probably sleepiness-related motor vehicle accident 12 years ago at 4 PM while driving home from work. His score on the Epworth Sleepiness Scale was 17 (out of a maximum 24 possible), which was indicative of hypersomnia. His family history of sleep disorders included a son who was treated with CPAP for sleep apnea. Headache diagnoses included probable sleep apnea headache versus chronic tension-type headache versus medication overuse headache and history for episodic cluster headache. Polysomnography indicated OSA, he met all criteria on the STOP-Bang (1snoring, 1tiredness, 1observed apnea, 1hypertension, 1BMI, 1age, 1neck circumference >17 in, 1male gender), and he was diagnosed with nocturia. A split-night sleep study was conducted after OSA was diagnosed and deemed severe. During the initial approximately 3.5 hours of testing, the patient showed an apnea-hypopnea index of 65 events per hour, with oxygen desaturation to 66% and respiratory-related arousals. His CPAP was titrated to 14 cm H2O, with normalization of respiratory
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parameters in REM and non-REM sleep while supine. Sleep architecture included 5.3 hours net sleep, 71% of which occurred in bed, with 21% slow wave or stage 3 sleep and an extended REM cycle after CPAP, suggesting REM rebound. His arousal index was 38.3 and was mostly associated with pre-CPAP respiratory events. No periodic limb movements or other abnormalities were observed. He was prescribed CPAP at 14 cm H2O. At 30-day follow-up, his daily headaches were resolved and his subjective sleep and nocturia were improved. His objective CPAP adherence was 100% (30 of 30 days), with a mean daily use of 4 hours and 40 minutes per night. Daytime sleepiness was improved but not resolved, with a score on the Epworth Sleepiness Scale of 12 of 24. His treatment plan included long-term CPAP use, monitoring of mild persistent sleepiness, weight management, and determining whether treatment of apnea impacted cluster recurrence.
Current controversies and future considerations Sleep has been identified among risk factors for transformation from episodic to chronic headache in a sort of “disease progression” model. Lipton and Pan39 originally postulated that migraine might be conceptualized as a chronic progressive disorder. The progression or “chronification” of headache from episodic to “chronic daily headache” is a well-described clinical phenomenon, in which episodic migraine transforms to chronic daily headache over the span of months or years. Potential mechanisms for headache chronification have been described elsewhere,40 but progression is thought to be a consequence of the cortical spreading depression mechanisms that generate the migraine attacks; a function of the activations generated by the attacks, such as lesions in the periaqueductal gray area; and genetic and/or environmental risk factors. Snoring and sleep disturbance specifically were identified among risk factors for progression. Scher and colleagues41 found that patients with chronic daily headache were 3.3-fold more likely to be daily snorers than controls; the association was independent of headache type, gender, or age; and obesity was an independent risk factor for progression. These investigators and Wiendels and colleagues42 have also identified sleep disturbance as a significant risk factor for progression. Other risk factors included medication overuse, stress, psychiatric comorbidity, and obesity. Understanding the link between risk factors and headache may yield novel preventive and therapeutic approaches in the management of headache. Sleep and other modifiable risk factors may be potential targets for primary or secondary headache prevention rather than solely variables for management. Although yet untested in patients with headache, snoring interventions and sleep regulation strategies could be considered for prevention. The natural history of sleep-disordered breathing indicates a progression of simple snoring to OSA, influenced by aging and weight gain. Interventions aimed at weight loss, conservative measures for snoring, and basic sleep regulation warrant consideration. Longitudinal studies in the future would help determine if sleep regulation can reduce the risk of headache progression, but a fundamental shift from management to prevention could be realized currently.
REFERENCES
1. Poceta JS, Rains JC. Sleep and headache syndromes. Sleep Med Clin 2008;3(3): 427–41. 2. Rains JC, Poceta JS, Penzien DB. Sleep and headaches. Curr Neurol Neurosci Rep 2008;8:167–75. 3. Headache Classification Subcommittee of the International Headache Society. The international classification of headache disorders, second edition. Cephalalgia 2004;24(Suppl 1):1–151. 4. Smitherman TA, Maizels M, Penzien DB. Headache chronification: screening and behavioral management of comorbid depressive and anxiety disorders. Headache 2008;48:45–50.
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5. Martin PR, MacLeod C. Behavioral management of headache triggers: avoidance of triggers is an inadequate strategy. Clin Psychol Rev 2009;29:483–95. 6. Houle TT, Butschek RA, Turner DP. Stress and sleep predict headache severity in chronic headache sufferers. Pain, in press. 7. Nobre ME, Leal AJ, Filho PM. Investigation into sleep disturbance of patients suffering from cluster headache. Cephalalgia 2005;25(7):488–92. 8. Mitsikostas DD, Vikelis M, Viskos A. Refractory chronic headache associated with obstructive sleep apnoea syndrome. Cephalalgia 2007;28(2):139–43. 9. Boardman HF, Thomas E, Millson DS, et al. Psychological, sleep, lifestyle, and comorbid associations with headache. Headache 2005;45(6):657–69. 10. Vgontzas A, Lihong C, Merikangas KR. Are sleep difficulties associated with migraine attributable to anxiety and depression? Headache 2008;48(10):1451–9. 11. Ohayon MM. Prevalence and risk factors of morning headaches in the general population. Arch Intern Med 2004;164(1):97–102. 12. Barbanti P, Fabbrini G, Aurilia C, et al. A case-control study on excessive daytime sleepiness in episodic migraine. Cephalalgia 2007;27(10):1115–9. 13. Alberti A, Mazzotta G, Gallinella E, et al. Headache characteristics in obstructive sleep apnea and insomnia. Acta Neurol Scand 2005;111:309–16. 14. Holle D, Wessendorf TE, Zaremba S, et al. Serial polysomnography in hypnic headache. Cephalalgia 2011;31(3):286–90. 15. Evers S, Goadsby PJ. Hypnic headache: clinical features, pathophysiology, and treatment. Neurology 2003;60(6):905–9. 16. American Academy of Sleep Medicine. The International classification of sleep disorders. diagnostic and coding manual. 2nd edition. Westchester (IL): American Academy of Sleep Medicine; 2005. 17. Brennan KC, Charles A. Sleep and headaches. Semin Neurol 2009;29(4):406–18. 18. Aurora SK, Barrodale PM, Tipton RL, et al. Brainstem dysfunction in chronic migraine as evidenced by neurophysiological and positron emission tomography studies. Headache 2007;47(7):996–1003 [discussion: 1004–7]. 19. May A, Matharu M. New insights into migraine: application of functional and structural imaging. Curr Opin Neurol 2007;20(3):306–9. 20. Vetrugno R, Pierangeli G, Leone M, et al. Effect on sleep of posterior hypothalamus stimulation in cluster headache. Headache 2007;47(7):1085–90. 21. Wei H, Zhao W, Wang YX, et al. Pain-related behavior following REM sleep deprivation in the rat: influence of peripheral nerve injury, spinal glutamatergic receptors and nitric oxide. Brain Res 2007;1148:105–12. 22. Roehrs T, Hyde M, Blaisdell B, et al. Sleep loss and REM sleep loss are hyperalgesic. Sleep 2006;29(2):145–51. 23. Smith MT, Edwards RR, McCann UD, et al. The effects of sleep deprivation on pain inhibition and spontaneous pain in women. Sleep 2007;30(4):494–505. 24. Silberstein SD, Lipton RB, Dalessio DJ. Overview, diagnosis, and classification of headache. In: Silberstein SD, Lipton RB, Dodick DW, editors. Wolff’s headache and other head pain. 8th edition. Oxford University Press; 2007. 25. Abrishami A, Khajehdehi A, Chung F. A systematic review of screening questionnaires for obstructive sleep apnea. Can J Anaesth 2010;57(5):423–38. 26. Flemons WW, Whitelaw WA, Brant R, et al. Likelihood ratios for a sleep apnea clinical prediction rule. Am J Respir Crit Care Med 1994;150(5 Pt 1):1279–85. 27. Chung F, Yegneswaran B, Liao P, et al. STOP questionnaire: a tool to screen patients for obstructive sleep apnea. Anesthesiology 2008;108:812–21. 28. Ong TH, Raudha S, Fook-Chong S, et al. Simplifying STOP-Bang: use of a simple questionnaire to screen for OSA in an Asian population. Sleep Breath 2010;14:371–6.
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29. Silva GE, Vana KD, Goodwin JL, et al. Identification of patients with sleep disordered breathing: comparing the Four-Variable screening tool, STOP, STOP-Bang, and Epworth Sleepiness Scales. J Clin Sleep Med 2011;7(5):467–72. 30. Rains JC, Poceta JS. Headache and sleep disorders: review and clinical implications for headache management. Headache 2006;46(9):1344–61. 31. Rains JC, Poceta JS. Sleep and headache. Curr Treat Options Neurol 2010;12:1–15. 32. Morgenthaler TI, Kapen S, Lee-Chiong T, et al. Practice parameters for the medical therapy of obstructive sleep apnea. Sleep 2006;29(8):1031–5. 33. Calhoun AH, Ford S. Behavioral sleep modification may revert transformed migraine to episodic migraine. Headache 2007;47(8):1178–83. 34. Barloese M, Jennum P, Knudsen S, et al. Cluster headache and sleep, is there a connection? A review. Cephalalgia 2012;32(6):481–91. 35. Nath Zallek S, Chervin RD. Improvement in cluster headache after treatment for obstructive sleep apnea. Sleep Med 2000;1(2):135–8. 36. Paiva T, Farinha A, Martins A, et al. Chronic headaches and sleep disorders. Arch Intern Med 1997;157(15):1701–5. 37. Chervin RD, Zallek SN, Lin X, et al. Sleep disordered breathing in patients with cluster headache. Neurology 2000;54(12):2302–6. 38. Kiely JL, Murphy M, McNicholas WT. Subjective efficacy of nasal CPAP therapy in obstructive sleep apnoea syndrome: a prospective controlled study. Eur Respir J 1999;13(5):1086–90. 39. Lipton RB, Pan J. Is migraine a progressive disease? JAMA 2004;291(4):493–4. 40. Bigal M, Lipton RB. Concepts and mechanisms of migraine chronification. Headache 2008;48:7–15. 41. Scher AI, Lipton RB, Stewart WF. Habitual snoring as a risk factor for chronic daily headache. Neurology 2003;60(8):1366. 42. Wiendels NJ, Neven AK, Rosendaal FR, et al. Chronic frequent headache in the general population: prevalence and associated factors. Cephalalgia 2006; 26(12):1434–42.