Polysomnography in Hypnic Headache Syndrome. David W. Dodick, MD

Transcription

1 Case Report Polysomnography in Hypnic Headache Syndrome David W. Dodick, MD Hypnic headache syndrome is an unusual chronic headache that usually begins after age 60 years and occurs exclusively during sleep. Despite the relationship between the headache and sleep, no formal sleep evaluation with overnight polysomnography has been reported for this syndrome. Three patients with long-standing hypnic headache underwent overnight polysomnography. The results were quite variable, ranging from normal to marked sleep insufficiency. A hypnic headache was captured in one patient arising out of rapid eye movement sleep at a time of severe oxygen desaturation. Formal sleep evaluation should be considered in patients with hypnic headache because there may be pathophysiologic and therapeutic implications. Key words: headache, sleep test, pathophysiology, polysomnography, treatment Abbreviations: REM rapid eye movement, CPAP continuous positive airway pressure, OSA obstructive sleep apnea (Headache 2000;40: ) Hypnic headache syndrome is a rare, recurrent, benign headache disorder that occurs exclusively during sleep and usually begins after age 60 years. It was first characterized by Raskin 1 in 1988 in 6 patients who were awakened regularly from nocturnal sleep by a short-lasting headache. Since then, 35 more patients have been reported, and the clinical spectrum has expanded, as have the therapeutic options available. 2-7 Although it has been suggested that hypnic headache syndrome is likely a rapid eye movement (REM)- related sleep phenomenon, 1,8 no formal sleep evaluation with overnight polysomnography has been performed in any of the reported patients. The results of three patients with hypnic headache syndrome who underwent overnight polysomnography are reported and the implications of the findings discussed. From the Department of Neurology, Mayo Clinic Scottsdale, Ariz. Address all correspondence to Dr. David W. Dodick, Mayo Clinic Scottsdale, East Shea Boulevard, Scottsdale, AZ Accepted for publication May 21, CASE HISTORIES Patient 1. A 59-year-old airport machinist presented with a 9-year history of severe nocturnal headaches. They occurred only during nocturnal sleep and usually began between 30 minutes and 4 hours after he fell asleep. The pain was described as a steady throbbing headache of severe intensity that was usually located in the left temporal region. The headache often lasted 30 to 40 minutes but has persisted for up to 3 hours. The patient reported that he feels the need to get out of bed and sit upright during the headache. After the headache resolves, he usually goes back to sleep but often awakens several hours later with a similar headache. The headaches are not associated with nausea, vomiting, photophobia, phonophobia, or ipsilateral autonomic symptoms (lacrimation, rhinorrhea). None of the following nondrug and pharmacologic therapies were effective: ice, heat, oxygen by nasal cannula (7 L over 15 minutes), methysergide, prednisone, imipramine, clonazepam, verapamil, metoclopramide, sumatriptan (50-mg tablets and 20-mg nasal spray), indomethacin, and zolpidem tartrate. Lithium was helpful initially in slightly reducing the frequency of the headaches, but increasing dosages appeared to be necessary and dose-limiting side effects occurred so this treatment was discontin- 748

2 Headache 749 ued. Operations on the maxillary sinus were performed twice (1993 and 1998), but they did not improve the headaches. The patient had a history of snoring, but this improved after the sinus operation. There is no history of obstructive sleep apnea. His medical history is significant for a 20-pack-year history of tobacco use. He was not taking any medication at the time of his evaluation. The results of the general physical and neurologic examinations were normal. Gadolinium-enhanced magnetic resonance imaging (MRI) of the brain showed no abnormality. Overnight polysomnography revealed grade 5 snoring and severe obstructive apnea, with 31.3 REMrelated apneic spells per hour and a mean oxygen saturation (pulse oximetry) of 69.5% (low, 51.2%) during REM. The arousal index (number of arousals per hour) was 9.1, all of which were due to disordered breathing. The patient awoke with a severe headache 51 minutes after the onset of sleep, and this coincided with the onset of the first REM period. The patient received treatment with nasal continuous positive airway pressure (CPAP) (9 cm H 2 O pressure) and supplemental oxygen at 2 L. The headaches resolved immediately, and he has been headache-free for 6 months. Patient 2. A 68-year-old woman presented with a 6-year history of nocturnal headaches that awaken her from sleep. The headaches have occurred almost every night and usually begin between 3 am and 4 am. The headache is diffuse, constant (nonpulsatile), of moderate intensity, and without associated nausea, photophobia, phonophobia, ptosis, lacrimation, or rhinorrhea. The intensity increases if she remains supine, and the headache is better if she is upright or at an inclined angle. Typically, she gets out of bed and takes buffered aspirin, and the headache resolves within 30 to 60 minutes. About 30% of the time after she again falls asleep, she awakens with a similar headache. The patient usually is able to return to sleep and awaken without headache. She has a history of tension-type headaches that occur infrequently and are distinctly less severe than the nocturnal headaches. Her medical history is remarkable for a corneal transplant in 1998 and a lumbar diskectomy. She does not take any medication and has no family history of headache. The results of general physical and neurologic examinations were normal. Gadolinium-enhanced MRI of the brain showed no abnormality. The average blood pressure with ambulatory blood pressure monitoring was 137/67 mm Hg. Overnight polysomnography showed a sleep efficiency of only 66.4%. There was no evidence of significant sleep-disordered breathing or nocturnal oxygen desaturation and only mild (grade 1) snoring. Total sleep time was minutes, 14.2% of which was REM sleep. The patient did not experience a headache during the study. Treatment was initiated with indomethacin, 25 mg, at bedtime, and during the next 2 weeks, she experienced only three nocturnal headaches. The dosage was increased to 75 mg of sustained-release indomethacin, and this eliminated the nocturnal headaches. However, daytime headaches developed, beginning around noon and continuing throughout the day. These headaches resolved after indomethacin was discontinued. Treatment with melatonin, 3 mg, at bedtime was begun, and headache severity decreased from moderate to mild and duration decreased to 15 to 20 minutes. The dose was increased to 6 mg, which rendered her headache-free over a 4-month period. Patient 3. A 46-year-old optometrist presented with a 7-year history of nocturnal headaches, which occurred approximately 4 nights per week and usually awakened him from sleep between 4 am and 6 am. Only an occasional headache began earlier in the night (2 am). The headaches were generalized, of moderate severity, described as dull and steady, and lasted between 2 and 4 hours, although rarely they resolved over a 6-hour period. No vomiting, photophobia, or phonophobia was associated with the headaches, but he occasionally experienced nausea. Alcohol ingestion the night before may have exacerbated the headache. The patient often arose from bed and usually took a shower. Ibuprofen taken symptomatically and amitriptyline for prophylaxis had no effect. His wife has complained about his snoring, but this had decreased over the year before his evaluation. His medical history was notable for hyperlipidemia, and his family history was significant for migraine (sister and mother). He was taking atorvastatin (Lipitor), and ibuprofen as needed. The results of

3 750 October 2000 general physical and neurologic examinations were normal. Gadolinium-enhanced MRI of the brain and cervical spine did not show any abnormality. Overnight polysomnography demonstrated minimal snoring only when the patient slept on his back. Very occasional snort arousals were noted with the patient supine, but apnea or hypopnea was not found. Only 7% of 14 arousals per hour were breathingrelated. Periodic limb movements were not seen. Sleep efficiency was low at 82%, because of 70 minutes of wakefulness related to dyspepsia. The patient did not report any headache. Overall, the study showed no evidence for significant sleep-disordered breathing events. Neither a trial of caffeine (cup of coffee) before bedtime nor 3 mg of melatonin at bedtime alleviated his headaches. Treatment with sustained-release indomethacin, 75 mg, each evening was initiated in October 1998, and the patient has been headache-free for 12 months. COMMENTS The three cases reported herein are the first examples of stereotyped hypnic headache in which overnight polysomnography was performed. These studies showed a spectrum of findings. That a relationship exists between headache and sleep has been known for more than a century, yet the exact nature of this relationship is an enigma. A paradoxical relationship between migraine and sleep has been recognized for some time. Although a change in the amount of sleep (deprivation or excess) often triggers an attack of migraine, sleep itself has long been known to be a powerful method for terminating an attack. Several well-defined primary headache syndromes such as cluster headache and chronic paroxysmal hemicrania may predominate during nocturnal sleep, and migraine frequently occurs during sleep or upon awakening. 9 However, nowhere is the relationship between sleep and headache better illustrated than in hypnic headache syndrome, in which the headache occurs only during sleep and at no other time. Because of this exclusive relationship, hypnic headache syndrome offers perhaps the best opportunity to analyze and to begin to clarify the relationship between headache and sleep. To date, 41 patients with this syndrome have been reported; yet none of them were reported to have had a formal sleep evaluation. 1-8 In the present series, a nocturnal headache was captured in only one patient (patient 1). This patient had stereotyped nocturnal headaches almost nightly for 9 years, and trials of multiple medications had failed except for lithium, which initially provided some benefit. While undergoing polysomnography, the patient awoke with a typical headache during the onset of the first REM period, at which time there was severe oxygen desaturation due to obstructive sleep apnea (OSA). Because of the patient s obesity, history of snoring, and mild daytime sleepiness, an underlying sleep-related breathing disorder might have been suspected; however, the snoring and mild daytime sleepiness were not prominent and were elicited only after careful historical inquiry. Although most reviews of OSA have listed headache as a common symptom, the characteristic clinical features of the headaches have not been well defined. The association is based on several small case series that have indicated that about 36% of patients with OSA report morning headaches The largest review, based on a detailed sleep questionnaire and polysomnographic results, reported an 18% incidence of morning headache among patients with OSA, compared with 6% among controls and 26% to 30% among patients with other sleep-related breathing disorders or primary sleep disorders. 13 In a prospective study of 19 patients with headache with snoring, apnea, or excessive daytime somnolence, 17 had OSA; of the 14 patients given CPAP, 4 had marked improvement in headache severity and 3 had moderate improvement. 14 Most of these patients had mixed or vascular headaches, and it was not clear whether any had strictly nocturnal headache. Because of the marked and sustained response of patient 1 to CPAP and supplemental oxygen, it is clear that oxygen desaturation was important in the genesis of his headaches. However, it is unlikely to be the only factor. He did not complain of headache on awakening or during the day, which is associated more commonly with OSA. Although he had severe OSA and desaturation during all stages of sleep, it was only during REM sleep that his headache began.

4 Headache 751 Several primary headache disorders, such as cluster headache, chronic paroxysmal hemicrania, and migraine, occur predominantly during REM sleep. 9 It has also been proposed that hypnic headache syndrome is likely a REM-related phenomenon, because of the timing of the headaches, their occurrence during daytime naps, the propensity for the headache to recur cyclically throughout the night at almost 2-hour intervals, and the propensity for some patients to awaken with a headache during a vivid dream. 1,2,8,15 Possibly the changes in cerebral blood flow, intraocular pressure, and oxygen tension that occur during REM sleep are magnified in patients with OSA. This constellation of factors may precipitate headache in predisposed persons. Rapid eye movement sleep is associated with increased cerebral blood flow, decreased systemic concentrations of serotonin, profound sympathetic activation, and marked changes in the activity of neurons in the dorsal raphe and locus ceruleus nuclei. 16 Activity in these nuclei is greatest during arousal, decreases during quiet waking, decreases further during non-rem sleep, and is absent during REM sleep. In conjunction with the periaqueductal gray matter, the dorsal raphe and locus ceruleus nuclei represent an integral part of the central antinociceptive network and recently have become the focus of studies of migraine. Positron emission tomographic studies have demonstrated persistent activity in the region of these nuclei both during and immediately after a migraine attack, 17 suggesting that the brain stem regions crucial for regulating the stage of sleep may also have a pivotal role in either the initiation or termination of an acute attack of migraine. Indeed, migraine may well be a defect in the normal control mechanisms for suppressing nociceptive input, because in experimental animals these nuclei gate trigeminal nociceptive information. In patient 2, overnight polysomnography showed a marked decrease in sleep efficiency. Ironically, the patient s subjective report was that this was one of the best night s sleep she had had in a long time. This is not altogether unexpected because sleep in the elderly is characterized by a sharp decrease in slow wave sleep and an increase in nocturnal awakenings. The elderly also appear to have a disturbance in sleep-wake rhythms, with increased napping during the day and possibly an advanced sleep phase pattern. 18 Although it is debated whether total 24-hour sleep time is reduced, nocturnal sleep does diminish in old age. This disturbance in circadian sleep-wake rhythms mirrors the decrease in the number of cells in the suprachiasmatic nucleus (site of the biological clock) and the decrease in the nocturnal secretion of melatonin that occur with advancing age. 19 In light of the increasing data that support a role for melatonin in the pathogenesis and therapy for several headache disorders, including cluster headache and migraine, the remarkable and sustained response that patient 2 had to melatonin treatment underscores the important relationship between the circadian biology of the sleep-wake cycle and the genesis of certain primary headache disorders This patient represents the first reported case of hypnic headache responsive to melatonin. Patient 3, a 46-year-old man, is one of the youngest patients reported with hypnic headache syndrome; most of the reported patients have been older than 60 years. Although this patient had a history of snoring, the overnight polysomnographic results were normal. This finding suggests an intrinsic relationship between sleep and headache and is contrary to the proposal that morning or nocturnal headaches are often or frequently related to a primary sleep disturbance, a viewpoint which is based on studies that involved patients with chronic ill-defined headaches (vascular, tension, mixed, and psychogenic), often with analgesic abuse Also, these studies frequently did not control for other coexisting conditions such as depression, anxiety, or other medical problems, which themselves lead to syndromes of insufficient sleep. On the contrary, clearly defined episodic primary headache syndromes are rarely associated with significant sleep disruption or sleep disorders, despite the fact they may occur predominantly or even exclusively during sleep. In summary, a detailed sleep history is an important part of the evaluation of patients with hypnic headaches. Although most patients with a well-defined primary headache syndrome in which attacks are prominent during sleep or upon awakening are unlikely to have a major sleep disorder, overnight polysomnography may provide important clinical information that

5 752 October 2000 may have therapeutic relevance, especially when the history suggests an underlying sleep disorder. Obstructive sleep apnea can masquerade as hypnic headache, as demonstrated in patient 1, highlighting the importance of a careful sleep history and recognition of the risk factors for OSA. Melatonin and indomethacin may be effective therapies in this syndrome. Further study is necessary to help clarify the relationship between these headaches and REM sleep, which may help shed light generally on the biologic association between sleep and headache. REFERENCES 1. Raskin NH. The hypnic headache syndrome. Headache. 1988;28: Dodick DW, Mosek AC, Campbell JK. The hypnic ( alarm clock ) headache syndrome. Cephalalgia. 1998; 18: Ivanez V, Soler R, Barreiro P. Hypnic headache syndrome: a case with good response to indomethacin. Cephalalgia. 1998;18: Morales-Asin F, Mauri JA, Iniguez C, Espada F, Mostacero E. The hypnic headache syndrome: report of three new cases. Cephalalgia. 1998;18: Gould JD, Silberstein SD. Unilateral hypnic headache: a case study. Neurology. 1997;49: Queiroz LP, Coral LC. The hypnic headache syndrome a case report [abstract]. Cephalalgia. 1997; 17: Skobieranda FG, Lee TG, Solomon GD. The hypnic headache syndrome: six additional patients [abstract]. Cephalalgia. 1997;17: Newman LC, Lipton RB, Solomon S. The hypnic headache syndrome: a benign headache disorder of the elderly. Neurology. 1990;40: Sahota PK, Dexter JD. Sleep and headache syndromes: a clinical review. Headache. 1990;30: Guilleminault C, van den Hoed J, Mitler MM. Clinical overview of the sleep apnea syndromes. In: Guilleminault C, Dement WC, eds. Sleep Apnea Syndromes. New York: Alan R Liss; 1978: Mathew NT, Frost JD. Sleep apnea and other sleep abnormalities in primary headache disorders [abstract]. Headache. 1984;24: Boutros NN. Headache in sleep apnea. Tex Med. 1989;85: Aldrich MS, Chauncey JB. Are morning headaches part of obstructive sleep apnea syndrome? Arch Intern Med. 1990;150: Poceta JS, Dalessio DJ. Identification and treatment of sleep apnea in patients with chronic headache. Headache. 1995;35: Dodick DW. The hypnic headache syndrome. In: Gilman S, Goldstein GW, Waxman SG, eds. Neurobase. San Diego: Arbor Publishing; Somers VK, Dyken ME, Mark AL, Abboud FM. Sympathetic-nerve activity during sleep in normal subjects. N Engl J Med. 1993;328: Weiller C, May A, Limmroth V, et al. Brain stem activation in spontaneous human migraine attacks. Nat Med. 1995;1: Roth T, Roehrs TA, Carskadon MA, Dement WC. Daytime sleepiness and alertness. In: Kryger MH, Roth T, Dement WC, eds. Principles and Practice of Sleep Medicine. 2nd ed. Philadelphia: WB Saunders Co; 1994: Brzezinski A. Melatonin in humans. N Engl J Med. 1997;336: Brun J, Claustrat B, Saddier P, Chazot G. Nocturnal melatonin excretion is decreased in patients with migraine without aura attacks associated with menses. Cephalalgia. 1995;15: Leone M, D Amico D, Moschiano F, Fraschini F, Bussone G. Melatonin versus placebo in the prophylaxis of cluster headache: a double-blind pilot study with parallel groups. Cephalalgia. 1996;16: Leone M, Lucini V, D Amico D, et al. Twenty-fourhour melatonin and cortisol plasma levels in relation to timing of cluster headache. Cephalalgia. 1995;15: Nagtegaal JE, Smits MG, Swart AC, Kerkhof GA, van der Meer YG. Melatonin-responsive headache in delayed sleep phase syndrome: preliminary observations. Headache. 1998;38: Paiva T, Martins P, Batista A, Esperanca P, Martins I. Sleep disturbances in chronic headache patients: a comparison with healthy controls. Headache Q. 1994; 5: Paiva T, Batista A, Martins P, Martins A. The relationship between headaches and sleep disturbances. Headache. 1995;35: Paiva T, Farinha A, Martins A, Batista A, Guilleminault C. Chronic headaches and sleep disorders. Arch Intern Med. 1997;157: