Abstract
Introduction
Hypnic headache is a relatively rare and, most likely, underdiagnosed disorder originally described by Raskin in 1988 (1). From the small number of cases described since then, it is reasonable to conclude that most patients are women, aged 50 and over, who consistently wake up during the night with bilateral, nonpulsatile headache. The intensity of the headache is moderate to severe, not accompanied by autonomic phenomena, and lasts for 15 min to 6 h. The nightly, or nearly nightly pattern of the headache, always waking up the patient virtually at the same time, has rendered it the name ‘alarm-clock headache’ (2). It has also been described that an identical headache could wake the patient up during daytime naps (2).
The diagnosis is essentially one of exclusion, since many other headaches, primary and secondary alike, may waken up a patient. The diagnosis is usually made after years or even decades of a continuous pattern of headache during sleep, when other causes of headache have been excluded. Considering that patients with hypnic headache may also suffer from other forms of primary headache, the history and progression of the headache, as well as the diary, are essential for the correct diagnosis (2).
The pathogenesis of hypnic headache is still unknown. It has been postulated that hypnic headache could be a sleep disorder rather than a primary headache. Usually occurring in patients aged 50 and over, when the sleeping pattern may be physiologically and haemodynamically altered, this headache could be associated with particular phases of sleep, especially the REM stage (3). Very recently, three cases of hypnic headache underwent polysomnographic studies, and the results were variable (4). A recent case report of one case of hypnic headache showed arousal due to headache at stage three slow wave sleep (5). Reports are still coming on patients from different countries (6) and our aim is to add to the present literature with our series of eight Brazilian patients suffering from hypnic headache. These patients were evaluated at the Department of Neurology in Escola Paulista de Medicina, São Paulo, Brazil. These patients were diagnosed, evaluated, treated and are being clinically followed up at the Division for Diagnosis and Treatment of Headache.
Patients and methods
Eight patients were evaluated, seven females and one male. They all had the pattern typical for hypnic headache and other possible causes for their headaches were excluded. The diagnosis of hypnic headache was confirmed by diaries completed by the patients.
Results
The clinical characteristics of these eight patients are summarized in Table 1 and a short description of each case is detailed below. The average age was 58 years (range 51–74 years). On average, the diagnosis of hypnic headache was made six years after the headache started (range 1–15 years). Six of these patients had daily headache, while two woke up with the headache twice a week at least.
Clinical characteristics of eight consecutive patients presenting Hypnic headache syndrome
All patients had normal neurological examination and CT scans. They are still under our care.
Short description of cases
Case 1
Female, 59 years old, with approximately 10-year history of headache every night, always at 1:00am. The headache had always been severe in intensity, lasting one to six hours, located in the frontal area bilaterally and with a predominant burning sensation. The headache could happen during daytime naps and also while the patient was dreaming. No medication improved the headache, although walking and drinking coffee could bring some benefit. Lithium (600 mg/day) initially reduced the frequency of pain by 50%, but the headache relapsed to its original pattern after a couple of months. No other medication brought any benefit.
Case 2
Female, 58 years old, a 1-year history of headache every night, at variable hours, lasting 4–6 h. The headache was severe in intensity and throbbing in character, and it was felt all over the head. The headache did not occur during daytime naps and no relationship had been observed with dreams. Getting up from bed and walking around the room could give provide relief. Amitriptyline 50 mg/day caused mild improvement (<50% decrease in the frequency of headache), but as this was the only medication that brought any relief, the patient is still using it.
Case 3
Male, 55 years old, with 3 years of throbbing headache that invariably occurred at 05.00 and lasted for 4 h. The pain was felt in both temporal regions, and was of moderate intensity. The headache could happen during naps and dreams and could only be improved by walking and drinking coffee. Flunarizine 10 mg/day caused a transient improvement in the frequency of headache, and no other medication has brought any benefit. The patient remains with daily headache despite temporary improvements with one or other drug that has been tried.
Case 4
Female, 74 years old, with a 13-year history of daily headache, always at 01.00, usually moderate in intensity, although it could occasionally be incapacitating, and lasting 5–6 h. The same headache could happen during daytime naps but it was not observed during dreaming periods. The pain was located bilaterally in the frontal region, and it was tight in character. There could be an improvement in the intensity of the headache with simple analgesics (containing caffeine?) but the patient did not make use of such analgesics very often. Taken on a daily basis, atenolol 50 mg/day could bring an improvement to the headache, of the order of 50% decrease in frequency.
Case 5
Female, 55 years old, with one and a half years of headache at least twice a week, always waking her up, albeit at different hours. This was a severe headache, located at both parietal areas, lasting at least 30 min and felt like an intense pressure. Drinking coffee and walking around could provide some degree of relief. No relationship was observed with daytime naps or dreams and, with the exception of this persistent headache, the patient had never had any other headache at any time in her life. Mild improvement was obtained by associating Lithium 600 mg/day with amitriptyline 25 mg/day. The patient remains on these medications, having less intense and less frequent headaches.
Case 6
Female, 54 years old, with a 2-year history of headache waking her up at 03.00, at least twice a week. The headache was moderate in intensity, feeling like stabs all over the head. The pain lasted for one hour and did not happen during daytime naps or specifically while dreaming. The patient observed that getting up from bed and walking could improve the intensity of the pain. Moderate relief was felt with Lithium 300 mg/day, but the patient did not increase the dose and has chosen not to take it any longer. Other possible prophylactic drugs caused only temporary relief.
Case 7
Female aged 51, who was seen because of acute episodes of unilateral cervical headache on the right side, spreading over the parietal area of the same side. The headache was associated with straining movements of the right arm. The patient was a schoolteacher who made continuous use of blackboard and chalk. Rofecoxib 50 mg/day and two sessions of C1-C2 blockade caused complete remission of this headache, though it returned six months later, also related to her work. When questioned, the patient reported yet another headache, with completely different features from the pain that had made her seek the present medical help. For one year and eight months the patient had been suffering from daily headaches, which invariably woke her up at 06.00, as well as during daytime naps. These were severe, bilateral headache episodes, located bilaterally over the frontal region, feeling like intense pressure. Mild relief could be obtained with getting up from bed, moving around and taking a dose of simple analgesics. She had previously consulted General Practitioners who had prescribed benzodiazepinic drugs to no avail. As yet, the patient has not benefited from any drugs prescribed on a prophylactic basis, although temporary improvement has been observed with amitriptyline and atenolol.
Case 8
Female, 62 years old, with a 15-year history of headache that woke her up every night, at different hours. The headache used to wake her up from daytime naps as well, and it could occur while dreaming. It felt like pressure all over the head and was of moderate intensity, lasting one to three hours. Mild relief could often be obtained by getting up from bed to walk. Moderate benefit was observed with indomethacin 50 mg and caffeine 100 mg taken together before bedtime, but the patient could not tolerate such treatment due to gastric pain.
Only one patient presented another form of headache associated with the disorder being studied. She was suffering from cervicogenic headache for two weeks and mentioned that this was clearly different from her usual ‘night headache’, which had started one year and eight months before.
All patients presented bilateral headache. The localization of the pain was very variable. While three patients agreed that the pain was in the frontal area, the other five patients reported the pain in other areas of the head. The quality of the pain was also variable. Two patients reported it to be pulsatile or throbbing, three patients said it had pressure or tightness qualities, one patient mentioned it as being like stabbing, and the other said it was a burning sensation. In all cases the headache lasted less than six hours.
Night sleep was the precipitating factor in all cases, while five patients also reported daytime naps as a possible precipitator. Five patients woke up always at the same time between 01.00 and 06.00 with the headache, while three patients could not specify that the headache always happened at exactly the same time of the night. None of the eight patients presented autonomic phenomena prior to, during, or after the headache.
Three patients reported that they could improve if they got up and moved around, while three others noticed that, apart from moving around, they would improve if they took coffee. Two patients observed a degree of headache relief if they took analgesics.
Five of these patients were treated with lithium carbonate 300–600 mg/day, before bedtime. In one case an excellent response, i.e. complete remission of headache, to this treatment was observed. In another patient, the response was satisfactory, i.e. a decrement of 50% in the headache frequency, and therefore lithium was maintained. Not responding to this treatment with lithium or in cases where lithium was not a suitable option, the other patients were treated with bromazepan, flunarizine, gabapentin, amitriptyline, valproic acid, indomethacin and beta-blockers. The follow up of this series of cases is still relatively short, but it is now over six months for all patients. We continue to pursue an adequate treatment for them, since some patients have shown initial improvement with one or other drug, but hypnic headache has relapsed during the follow up. Except for one case of complete remission of this nightly occurring headache, we have not observed any other case of headache suppression by medications or otherwise.
Discussion
In accordance with the more recent literature (1–3), the majority of our patients were women aged 51 or more. Frequency of headache, its location and the quality of pain were variable among our patients, but always the same for each patient. In some cases, the duration of pain was variable even for the same patient, and the time of occurrence was also variable for three of them. The severity of pain was considered at least moderate for the patients, who often had headache daily. As a consequence, quality of life and frustration with lack of diagnosis and therapeutic options rated highly among the patients in this group.
In accordance with the literature, our group of patients presented headache during daytime naps and sometimes relate it to dreaming (1). The relationship between headache or pain to dreams is intriguing to say the least (7–10). Dreams often happen during the REM stage of sleep, and they may happen in up to 40% of people during naps (11). Waking up with headaches at night from dreams and also from naps has already been observed by Dexter and Weitzman in 1970 (7) even before the initial description of the Hypnic Headache Syndrome by Raskin in 1988 (1). In 1975, Dexter and Riley (8) observed that in the REM stage, a more prolonged and severe pain might be necessary to arouse the individual from the inhibitory waking up mechanisms in action. We cannot elaborate further on the subject of headaches occurring during the REM stage of sleep in Hypnic Headache Syndrome as this evaluation has not yet been completed in our patients.
The majority of our patients reported headache relief if getting up and walking around as they woke up with pain. This finding may be related to an improvement of brain blood flow, which is known to change by posture, physical activity, and sleep stages through altered vascular tonus (12).
The most striking feature was the time taken to reach a diagnosis. It took at least one year for each case, and more than 10 years for three patients who had daily headaches at a specific time of the night. We believe that registration of headache patterns in diaries was the most important tool in our diagnosis. Once secondary causes of night headache were excluded, Hypnic Headache Syndrome was the obvious option.
With regard to treatment for this condition, except for one case of complete remission using lithium, we did not register any other such successful result. Therefore, we believe that a good response to lithium, caffeine or indomethacin cannot be part of the diagnostic criteria for this disease (13, 14).