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Unmasking the Cause of an "Alarm Clock" Headache

Unmasking the Cause of an "Alarm Clock" Headache

Primary care doctor: Because of the patient's age and the absence of a headache history, I first considered such secondary causes as tumor and temporal arteritis. However, MRI of the brain and erythrocyte sedimentation rate were normal. I now suspect a sleep-related headache because the attacks occur only at night and awaken the patient from a sound sleep. How can I determine which type of sleep-related headache is involved? Headache specialist:The first step is to assess the severity, pain location, and presence of autonomic features. "Nocturnal attack" headaches include hypnic headache, cluster headache, chronic and episodic paroxysmal hemicrania, and SUNCT (short-lasting, unilateral, neuralgiform hemicrania with conjunctival injection and tearing) syndrome. Patients with nocturnal attack headaches generally describe the pain as throbbing or stabbing. Cluster headaches and chronic and episodic paroxysmal hemicrania produce very severe pain; hypnic headaches and SUNCT syndrome headaches produce moderately severe pain.

syndrome headaches produce moderately severe pain. The pain of cluster headaches, chronic and episodic paroxysmal hemicrania, and SUNCT syndrome is typically unilateral at the orbit or temple. Patients with hypnic headaches commonly experience diffuse, dull or throbbing, global pain; unilateral pain is rare.1-4 Sleep-related headaches- with the exception of hypnic headaches-are associated with autonomic symptoms.

Doctor: Because my patient has no autonomic symptoms, hypnic headache is the most likely diagnosis. How common is this type of headache? Headache specialist: Raskin5 first described hypnic headache as a rare condition that primarily affects elderly women (the female-to-male ratio is 2:1). Recently, researchers have proposed that hypnic headache may be a spectrum disorder, because the headaches range from mild, bilateral, 5-minute attacks to severe, unilateral, throbbing attacks that can last up to 6 hours (Table).2Headache specialist: Researchers believe that fluctuations in the levels of serotonin and other brain neurotransmitters that occur during sleep can affect headaches.

In one study, researchers described the case of a 79-year-old woman with an 11-year history of nocturnal headaches that suggested hypnic headache.6 A polysomnographic study showed arousal at stage 3 slow wave sleep because of a headache episode. Although this finding may have been nonspecific, it suggests the possible relationship between stage 3 slow wave sleep and hypnic headache.7 In another report, the author conducted overnight polysomnographic studies of 3 patients with long-standing hypnic headache.8 The results ranged from normal to marked sleep insufficiency. A hypnic headache was revealed in 1 patient who awoke from rapid eye movement sleep at a time of severe oxygen desaturation. The author suggested that formal sleep evaluation be considered for patients with hypnic headache because there may be pathophysiologic and therapeutic implications. Doctor: What is the pathophysiology of hypnic headache? Headache specialist:We don'tyet have all the answers. Raskin wrote that the pathophysiology of the hypnic headache resembles that of the chronic form of cluster headache (migrainous neuralgia).5 The mechanism of these 2 syndromes may be similar because both appear to involve the pacemaking mechanism in the hypothalamus that controls circadian rhythm. This theory is supported by the remarkable response of both types of headache to lithium therapy. Since the hypothalamic pacemaker is serotonergically innervated and lithium has been shown to enhance serotonergic neurotransmission, it seems reasonable to suppose that perturbed serotonergic neurotransmission underlies both disorders. Substantial laboratory evidence indicates that lithium stabilizes and enhances serotonergic neurotransmission in the hippocampus, the site at which serotonin receptors are down-regulated during lithium treatment. This may also slow and alter circadian rhythms. Doctor: What dosage of lithium is recommended for patients with hypnic headache? Are effective alternatives available? Headache specialist: Hypnic headaches may be treated with lithium at a starting dosage of 300 mg every night that is slowly increased to 900 mg/d. However, the side effects of lithium, such as tremor and impaired memory, make it intolerable for some elderly patients. Indomethacin may be an option for some patients who are not helped by lithium. In one study, indomethacin was effective in 7 patients with hypnic headache.9 Four patients had a substantial reduction in the frequency and severity of headaches, and 3 had complete suppression of headaches. However, 2 of those 3 experienced severe daytime headaches, which resolved when indomethacin was discontinued. Flunarizine, caffeine, or verapamil may also be tried as an alternative to lithium.7,9


1. Gould JD, Silberstein SD. Unilateral hypnic headache: a case study. Neurology. 1997;49:1749-1751.
2. Dodick DW, Mosek AC, Campbell JK. The hypnic (“alarm clock”) headache syndrome. Cephalalgia. 1998;18:152-156.
3. Ivanez V, Soler R, Barreiro P. Hypnic headache syndrome: a case with good response to indomethacin. Cephalalgia. 1998;18:225-226.
4. Morales-Asin F, Mauri JA, Iniguez C, et al. The hypnic headache syndrome: report of three new cases. Cephalalgia. 1998;18:157-158.
5. Raskin NH. The hypnic headache syndrome. Headache. 1988;38:534-536.
6. Arjona JA, Jimenez-Jimenez FJ, Vela-Bueno A, Tallon-Barranco A. Hypnic headache associated with stage 3 slow wave sleep. Headache. 2000;40:753-754.
7. Evers S, Goadsby PJ. Hypnic headache: clinical features, pathophysiology, and treatment. Neurology. 2003;60:905-909.
8. Dodick DW. Polysomnography in hypnic headache syndrome. Headache. 2000;40:748-752.
9. Dodick DW, Jones JM, Capobianco DJ. Hypnic headache: another indomethacin- responsive headache syndrome? Headache. 2000;40:830-835.
10. Goadsby PJ, Lipton RB. A review of paroxysmal hemicranias, SUNCT syndrome and other short-lasting headaches with autonomic feature, including new cases. Brain. 1997;120:193-209.
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