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Unmasking the Cause of an "Alarm Clock" Headache


Primary care doctor: Because of the patient’s age and theabsence of a headache history, I first considered such secondarycauses as tumor and temporal arteritis. However,MRI of the brain and erythrocyte sedimentation rate werenormal. I now suspect a sleep-related headache becausethe attacks occur only at night and awaken the patientfrom a sound sleep. How can I determine which type ofsleep-related headache is involved?

THE DIALOGUE:Primary care doctor: Because of the patient's age and theabsence of a headache history, I first considered such secondarycauses as tumor and temporal arteritis. However,MRI of the brain and erythrocyte sedimentation rate werenormal. I now suspect a sleep-related headache becausethe attacks occur only at night and awaken the patientfrom a sound sleep. How can I determine which type ofsleep-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 generallydescribe the pain as throbbing or stabbing. Cluster headachesand chronic and episodic paroxysmal hemicraniaproduce very severe pain; hypnic headaches and SUNCTsyndrome headaches produce moderately severe pain.

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

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

In one study, researchers described the case of a79-year-old woman with an 11-year history of nocturnalheadaches that suggested hypnic headache.6 A polysomnographicstudy showed arousal at stage 3 slow wave sleepbecause of a headache episode. Although this finding mayhave been nonspecific, it suggests the possible relationshipbetween stage 3 slow wave sleep and hypnic headache.7In another report, the author conducted overnightpolysomnographic studies of 3 patients with long-standinghypnic headache.8 The results ranged from normalto marked sleep insufficiency. A hypnic headache was revealedin 1 patient who awoke from rapid eye movementsleep at a time of severe oxygen desaturation. The authorsuggested that formal sleep evaluation be considered forpatients with hypnic headache because there may bepathophysiologic 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 clusterheadache (migrainous neuralgia).5 The mechanism ofthese 2 syndromes may be similar because both appear toinvolve the pacemaking mechanism in the hypothalamusthat controls circadian rhythm. This theory is supportedby the remarkable response of both types of headache tolithium therapy. Since the hypothalamic pacemaker isserotonergically innervated and lithium has been shownto enhance serotonergic neurotransmission, it seems reasonableto suppose that perturbed serotonergic neurotransmissionunderlies both disorders.Substantial laboratory evidence indicates that lithiumstabilizes and enhances serotonergic neurotransmission inthe hippocampus, the site at which serotonin receptorsare down-regulated during lithium treatment. This mayalso slow and alter circadian rhythms.Doctor: What dosage of lithium is recommended for patientswith hypnic headache? Are effective alternativesavailable?Headache specialist: Hypnic headaches may be treatedwith lithium at a starting dosage of 300 mg every nightthat is slowly increased to 900 mg/d. However, the sideeffects of lithium, such as tremor and impaired memory,make it intolerable for some elderly patients.Indomethacin may be an option for some patientswho are not helped by lithium. In one study, indomethacinwas effective in 7 patients with hypnic headache.9 Fourpatients had a substantial reduction in the frequency andseverity of headaches, and 3 had complete suppression ofheadaches. However, 2 of those 3 experienced severe daytime headaches, which resolved when indomethacin wasdiscontinued. Flunarizine, caffeine, or verapamil may alsobe tried as an alternative to lithium.7,9




Gould JD, Silberstein SD. Unilateral hypnic headache: a case study.




Dodick DW, Mosek AC, Campbell JK. The hypnic (“alarm clock”) headachesyndrome.


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Ivanez V, Soler R, Barreiro P. Hypnic headache syndrome: a case with goodresponse to indomethacin.


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Morales-Asin F, Mauri JA, Iniguez C, et al. The hypnic headache syndrome:report of three new cases.


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Arjona JA, Jimenez-Jimenez FJ, Vela-Bueno A, Tallon-Barranco A. Hypnicheadache associated with stage 3 slow wave sleep.


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Dodick DW, Jones JM, Capobianco DJ. Hypnic headache: another indomethacin-responsive headache syndrome?


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