Hypnic Headache - What do we know in 2022?

BACKGROUND: Hypnic Headache, also known as "alarm clock headache", is a rare primary headache disorder. It is characterized by frequently recurring headache attacks, which only develop during sleep, especially nighttime sleep. OBJECTIVE: This article gives a narrative review on the current knowledge about Hypnic Headache with a focus on secondary Hypnic Headache. METHODS: Based on literature research, using Pubmed and Google Scholar, latest case reports, studies, and systematic reviews about Hypnic Headache were analyzed and summarized focusing on therapeutic options and causes of secondary Hypnic Headache. CONCLUSION: Hypnic Headache mainly occurs in elderly patients. However, younger patients and children may also suffer from Hypnic Headache. Many different causes of secondary Hypnic Headache are described in the literature and ought to be ruled out before diagnosing primary Hypnic Headache. The pathophysiology of primary Hypnic Headache remains unclear, but a dysfunction of the hypothalamus seems to play a key role.

The prevalence of hypnic headache in Iceland.

OBJECTIVE: To determine the prevalence of hypnic headache. BACKGROUND: The exact prevalence of hypnic headache is unknown since there are no published population-based prevalence studies. METHODS: This study was a pilot for the SAGA cohort study, a population-based study on life stressors and various indices of health. Of 1398 invited adults, 921 (66%) participated; 402 men (average age 45.6 years, SD 13.2) and 519 women (52.6 years, SD 11.1). Subjects answered a headache questionnaire including a screening question for hypnic headache. "Do you have a headache that occurs only during sleep and causes wakening?". Diagnosis of hypnic headache was made by clinical interview using ICHD-3 criteria. RESULTS: Among 921 participants, six screened positive for hypnic headache, of those two 0.22% (95% CI 0.06-0.79%) had probable hypnic headache and none had definite hypnic headache. CONCLUSION: Confirming that hypnic headache is rare, these data suggest a 0.22% prevalence of probable hypnic headache.

Hypnic Headache Due to Hypoglycemia: A Case Report.

Hypnic headache (HH) is a rare primary headache disorder and pathophysiology is still poorly understood. It is considered a chronobiological disorder in almost all published cases. Few secondary cases have been described so far. We report a case of a 64-year-old woman presenting headaches exclusively during sleep and fulfilling the diagnostic criteria for HH, but a 72-hour glucose monitoring showed hypoglycemia episodes related to the onset of headaches. To our knowledge, this is the first report of symptomatic HHs associated with hypoglycemia and it suggests direct evidence of HH due to a metabolic disorder.

Case report of an alleviation of pain symptoms in hypnic headache via greater occipital nerve block.

Background Hypnic headache is a rare primary headache disorder with a few hundred described cases so far. Due to the fact that this headache disease is rare, there are no placebo-controlled oral medication studies. After all reported oral medication failed to control pain symptoms of a hypnic headache disease, we were able to reduce pain intensity and frequency via two greater occipital nerve (GON) blocks. Case We report on a 74-year-old patient diagnosed with hypnic headache in our headache outpatient department two years ago. Over a course of nine months none of the recommended oral drugs had an effect in pain alleviation and we decided to try an occipital nerve injection therapy. Two GON-blocks then led to a stable and significant pain reduction over the course of six months during monthly follow-ups. Conclusion GON block can be a successful therapeutic approach for the treatment of hypnic headache when oral medication fails.

No Pattern Alteration in Single Nocturnal Melatonin Secretion in Patients With Hypnic Headache: A Case-Control Study.

OBJECTIVE: To investigate headache-related serum melatonin levels and melatonin excretion rhythmicity in patients with hypnic headache (HH). BACKGROUND: Strict sleep dependency of headache attacks is a pathognomonic feature of HH. Changes in melatonin levels, a marker for circadian rhythm, are assumed to play a pivotal role in the pathophysiology of HH. METHODS: Serum melatonin levels were acquired in nine patients with HH and nine age- and gender-matched healthy controls over a 20-hour time period (12 pm, 4 pm, 7 pm, 10 pm, time of headache, and 8 am). RESULTS: No significant changes of melatonin levels could be detected comparing HH patients and healthy controls. Melatonin excretion rhythmicity was not significantly altered in patients with HH (Mean melatonin level in ng/mL ± SD, patients vs controls at 12 pm: 21.5 ± 9.5 vs 13.6 ± 6.3 [P = .077], 4 pm: 18.4 ± 8.4 vs 14.0 ± 4.7 [P = .222], 7 pm: 19.4 ± 5.1 vs 15.1 ± 4.5 [P = .094], 10 pm: 59.5 ± 45.0 vs 29.4 ± 12.7 [P =.136], headache time: 96.9 ± 68.3 vs 49.1 ± 22.8 [P = .94], and 8 am: 31.6 ± 18.3 vs 26.7 ± 15.6 [P = .489]). CONCLUSION: This study is not able to confirm a significant role of melatonin concentration changes in the pathophysiology of HH and vetoes that melatonin deficiency plays a major role in the pathophysiology of the disorder.

Long-Term Outcomes and Clinical Characteristics of Hypnic Headache Syndrome: 40 Patients Series From a Tertiary Referral Center.

OBJECTIVE: Hypnic headaches (HHs) are unique because of late life onset and characteristic periodic nocturnal awakening. We retrospectively identified 40 cases at a tertiary headache referral center over the course of 6 years and assessed response to conventional treatments. METHODS: This was a retrospective study in which patients were identified using primary and secondary ICD-9 diagnostic codes of HHs (339.81) from October 2008 until December 2014 using the International Classification of Headache Disorders II and III-beta criteria for diagnosis. Baseline characteristics were collected. Primary outcome was response to medications divided into 4 categories: complete response (headaches completely gone), moderate response (≥50% decrease in frequency), partial response (<50% decrease in frequency), no response. RESULTS: Forty (40) patients (80% females) were identified with HHs, and mean follow-up was 929 days (range 42-2555). Average age of headache onset was 62 years (range 44-86). Twenty (50%) patients had previous history of migraine, 5% had bilateral cranial autonomic features, and 40% underlying sleep abnormalities. The average duration per day and frequency per month of headaches were 186 minutes (range 30-720 minutes) and 21 days (range 5-30), respectively. Among 15 different medications tried, the best response was seen with lithium (7/10 [70%] complete response and 2/10 [20%] moderate response). With caffeine, there was a complete response in 6/21 (28%) and moderate response in 9/21 (43%) subjects. A telephone follow-up survey revealed that 5 patients in the bedtime caffeine group also benefited from taking a caffeinated drink at the time of awakening. CONCLUSIONS: HH is an infrequent primary headache disorder that can present with cranial autonomic features. It can persist for years in the elderly. Lithium appeared to be the most effective treatment option, followed by caffeine at bedtime. Caffeine ingestion on awakening with an HH also demonstrated benefit. Cervicogenic headaches in the elderly and presence of active migraine are major confounders in the diagnosis of HHs.

Case Report: Coexistence of SUNCT and Hypnic Headache in the Same Patient.

BACKGROUND: Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and hypnic headache (HH) are two exceedingly rare and distinctly classified primary headaches. The hypothalamus seems to be a crucial region involved in the pathophysiology of both conditions, but no cases of SUNCT and HH co-occurrence have been described so far. CASE RESULTS: A 49-year-old woman who has been suffering from SUNCT for years, with alternation of symptomatic periods and remissions, developed a new headache with different clinical features, presenting exclusively during sleep and with a dramatic responsiveness to caffeine, that met the diagnostic criteria for HH. CONCLUSIONS: The available literature suggests that SUNCT and HH are different conditions but the association in the same patient that we describe supports the concept that they are not mutually exclusive. Further studies are needed to establish if they share a common pathophysiological mechanism.

From wakefulness to sleep: migraine and hypnic headache association in a series of 23 patients.

OBJECTIVES/BACKGROUND: We analyzed characteristics of hypnic headache (HH), migraine and the relationship between both headaches in 23 patients. HH is an uncommon primary headache characterized by exclusively sleep-related attacks. Concurrence of other headaches, mainly migraine, has been reported, but relationship between both syndromes has rarely been considered. METHODS: We prospectively collected data in a headache outpatient office from January 2008 to September 2013. Demographic data and migraine and hypnic headache mean features were assessed. RESULTS: Twenty-three out of 2500 (0.92%) were diagnosed with HH or probable HH, and 16 of them (69.5%) had a history of migraine. Mean age at onset of HH and migraine was 56.2 ± 9.3 and 24.6 ± 12.2 years, respectively. In 12 cases, migraine attacks disappeared at 56.7 ± 9.8 years old. Regarding the relationship between both syndromes, in 10 patients, migraine disappeared and HH began immediately after. In 1 case there was a pain-free period, and in 5 an overlap between both headaches was registered. CONCLUSION: A history of migraine is common in HH patients in our series. Most frequent transition pattern was an immediate change between both syndromes. Hypnic headache and migraine might share a common pathophysiological predisposition.

Description of series of 10 patients with hypnic headache: Discussion of the diagnostic criteria.

INTRODUCTION: Hypnic headache is a rare primary headache. The diagnostic criteria of the International Headache Classification (IHS) for this condition are discussed, as they have been modified in the new edition of the 2013. PATIENTS AND METHODS: The clinical characteristics, and fulfilment of the criteria of the IHS classification in a series of 10patients diagnosed in our Headaches Clinic, are analyzed. RESULTS: The mean age of onset of symptoms was 52.1years (SD: 13.4; range: 28-69). The pain was reported as oppressive in 60% of the patients, and as sharp in 30%. The headache was described as holocranial in 60% and hemicranial in 40%. They occurred exclusively during night-time sleep in 80% of the patients. The mean duration of headache was 136.5minutes (range: 10-480). The mean number of days per month was 16.4 (range: 3-30), and 50% had less than 15 headache days per month. No patient had autonomic manifestations, 70% had phonophobia, 50% had photophobia, and 50% had both. All of them (100%) had a VAS score equal to or higher than 8. CONCLUSIONS: The criteria for hypnic headache of the new classification are best suited to the characteristics of these patients. Our results show the major changes in the criteria: pain is not always dull, headache frequency may be less than 15days a month, and it can occur in people under age 50. There may be phonophobia or photophobia only, or both. Although it does not form part of the diagnostic criteria, the pain intensity in our series was higher than described.

Pathophysiology of hypnic headache.

BACKGROUND: Hypnic headache (HH) is a rare primary headache disorder that is characterized by strictly sleep related headache attacks. PURPOSE: The underlying pathophysiology of HH is mainly enigmatic but some clinical characteristics such as circadian rhythmicity and caffeine responsiveness may point toward possible underlying mechanisms. METHOD: Current studies that deal with the pathophysiology of HH are summarized. Data on cerebral imaging, sleep, electrophysiology studies, effectiveness of drugs, and symptomatic headache types are discussed to illuminate underlying pathophysiologic mechanisms. CONCLUSION: HH can be clearly differentiated by its clinical presentation as well as imaging and electrophysiological study results from other primary headaches such as migraine or cluster headache. The underlying pathophysiology is still enigmatic but a hypothalamic involvement seems to be likely.

Hypnic headache: a review of clinical features, therapeutic options and outcomes.

BACKGROUND: Hypnic headache (HH), first reported in 1988, is a rare sleep-related headache disorder. In 2013 a new diagnostic criteria was proposed for HH in the International Classification of Headache Disorders, the third version beta (ICHD-3ß). PURPOSE: This review aimed to update the clinical characteristics, therapeutic options and clinical outcomes in patients with HH and also validate the new diagnostic criteria. METHODS: Based on a literature search in the major medical databases, we analyzed all case reports or case series on HH that have been published since the first description by Raskin. Except for symptomatic patients, all reported patients were included regardless of which diagnostic criteria were adopted. Four studies that reported the field-testing results of the ICHD-2 criteria were selected to validate the new ICHD-3ß criteria. RESULTS: In total, 250 adult and five childhood patients are described in this review. The majority of patients were elderly and their ages of onset were typically more than 50 years old (92%). Approximately 7.7% of patients had some trigeminal autonomic features, which are not permitted in the ICHD-3ß criteria. Compared with the ICHD-2 criteria, the diagnostic rate under the new criteria increased from 65% to 85% in recently reported cases. Randomized control trials both for acute and prophylactic treatment are lacking. Based on observational studies, the most effective acute treatment is caffeine and prophylactic medications in use are lithium, caffeine and indomethacin. Without treatment, the disease course is usually protracted but spontaneous remission did occur in 12 patients (4.8%). In those treated with prophylactic agents, no recurrence was noted in 43% of patients, even following withdrawal of medication. CONCLUSIONS: The new ICHD-3ß criteria are more sensitive and exhaustive for HH than the ICHD-2 criteria. Prophylactic treatment provides better outcomes; however, randomized controlled studies for treatment are needed to further verify the efficacy of the different drugs.

Hypnic headache.

BACKGROUND: Hypnic headache (HH) is a rare primary headache characterized by strictly sleep-related headache attacks. METHODS: This paper reviews the pertinent literature on HH. RESULTS: Disease information is mainly based on case reports and small case series (around 250 cases) published since its first description in 1988 by Raskin. HH usually starts over the age of 50. Frequency of patients with HH among patients consulting tertiary headache care centers is estimated from 0.07% to 0.35%, but exact prevalence of HH is unknown. Diagnostic criteria were recently updated by the third edition of the International Classification of Headache Disorders beta version (ICHD-3). Recent data suggest a possible hypothalamic involvement. CONCLUSION: Development of clinical research is needed to better understand the mechanisms of HH and to optimize treatment. Evidence for treatment data are missing, so treatment recommendations are based only on case reports or smaller open case series and reflect clinical experience. Caffeine can be used first line for acute treatment. Lithium and caffeine are possibly effective in prevention.

Headache in the elderly: characteristics in a series of 262 patients.

INTRODUCTION: Although headache prevalence decreases in patients older than 65, headaches are a common complaint and their different clinical and therapeutic features must be understood. This article analyses the clinical characteristics of elderly patients treated in an outpatient headache unit. METHODS: We collected demographic and clinical data from patients treated in a tertiary hospital headache unit between January 2008 and May 2013. Headaches were codified according to the International Classification of Headache Disorders, 2nd edition (ICHD-2). RESULTS: Of a total of 1868 patients treated, 262 patients (14%, 189 women and 73 men) were older than 65 years. Ninety-nine (68 women, 31 men, 5.3% of the total) were over 75. Headaches began after the age of 65 in only 136 patients (51.9%). The 362 headaches were codified as follows: 23.8% as Group 1 (Migraine) and 28.7% as Group 2 (Tension-type headache). We diagnosed 58 (16%) secondary headaches; 26 (7.2%) were classified as Group 13 (Cranial neuralgias) and 23 (6.4%) in Group 14 (Other headaches). Symptomatic medication overuse was detected in 38 patients (14.5%). We also identified headaches considered typical in the elderly, including chronic migraine (41 cases), hypnic headache (6), occipital neuralgia (4), SUNCT (2), cervicogenic headache (1), primary cough headache (1), and giant cell arteritis (2). CONCLUSIONS: Elderly patients were frequently treated in our outpatient headache unit. Tension-type headache was the most common diagnosis in this population. Geriatric headache syndromes such as hypnic headache or occipital neuralgia were also represented in our series.

Images: Sleep-related painful erection with concomitant hypnic headache.

Sleep-related painful erection (SRPE) is a parasomnia defined by the repetition of painful erections during rapid eye movement (REM) sleep. Hypnic headache (HH) is a primary headache occurring exclusively at night, often during REM sleep. We report the observation of a 33-year-old man with simultaneous SRPE and HH. Physical examination was normal. Comprehensive urological and endocrine explorations excluded other organic differential diagnoses. Polysomnography revealed several awakenings in REM, due to SRPE and concurrent HH. Medication by baclofen at bedtime seemed to have resulted in a decrease in SRPE episodes, confirmed by polysomnography, but at the cost of excessive daytime sleepiness, and was discontinued by the patient. Caffeine intake at bedtime was proposed, but the patient was reluctant because he was concerned about worsening insomnia. At 9-month follow-up, the patient had accepted his medical condition and was coping with both SRPE and HH. He felt reassured and wished no "overmedicalization." To our knowledge, the coexistence of both conditions has not yet been reported, yet their frequencies might be underestimated. We hypothesize a common underlying pathophysiology with a possible dysfunction of the vascular control and/or the autonomic nervous system and that could involve the hypothalamus. Somnologists should be aware of SRPE, potentially overlapping with HHs. SRPE should be considered in case of sleep-maintenance insomnia. Patient reassurance seems to be central in the care process of SRPE. CITATION: Moreau A, Monnier L, Medde A, Bourgin P, Ruppert E. Images: sleep-related painful erection with concomitant hypnic headache. J Clin Sleep Med. 2024;20(5):837-839.

Hypnic headache.

BACKGROUND: Hypnic headache (HH) is a rare primary headache disorder that is characterised by strictly sleep-related headache attacks. PURPOSE: Because of the low prevalence of this headache disorder, disease information is mainly based on case reports and small case series. This review summarises current knowledge on HH in regard to clinical presentation, pathophysiology, symptomatic causes and therapeutic options. METHOD: We review all reported HH cases since its first description in 1988 by Raskin. Broadened diagnostic criteria were applied for patient selection that slightly deviate from the current ICHD-II criteria. Patients were allowed to describe the headache character to be other than dull. Additionally, accompanying mild trigemino-autonomic symptoms were permitted. CONCLUSIONS: Mainly elderly patients are affected, but younger patients and even children might also suffer from HH. Headache attacks usually last between 15 and 180 minutes, but some patients report headache attacks up to 10 hours. Almost all patients report motor activity during headache attacks. Cerebral MRI and 24-hour blood pressure monitoring should be performed in the diagnostic work-up of HH. Other primary headache disorders such as migraine and cluster headache may also present with sleep-related headache attacks and should be considered first. Caffeine taken as a cup of strong coffee seems to be the best acute and prophylactic treatment option.

Ecchordosis physaliphora presenting as hypnic headache.

Ecchordosis physaliphora (EP) is a rare benign congenital hamartomatous lesion originating from remnants of the notochord. EP has never been associated with hypnic headache before. We report for the first time two cases of EP associated with an hypnic headache. The latter is a form of sleep-related nocturnal headache whose pathogenesis has not been fully elucidated. A 61-year-old woman and a 41-year-old man had been complaining of a dull headache that woke them up every night for many months. In both cases, an enlarged cystic lesion in the prepontine cistern, compatible with ecchordosis physaliphora, was found on brain MRI. A diagnosis of hypnic headache secondary to EP was made. Ecchordosis physaliphora presenting as hypnic headache had never been described before. The low prevalence of both conditions (EP and HH) and their presence in two cases might suggest a possible causal association between the two conditions.

Case report: Hypnic headache responds to agomelatine-a potential prophylactic treatment option.

Introduction: Hypnic headache (HH) is a rare primary headache that is characterized by strict sleep-related attacks. However, the pathophysiology of HH remains unclear. The nocturnal nature of this activity suggests a hypothalamic involvement. The pathogenesis of HH may involve the brain structure that regulates circadian rhythms and is related to an imbalance between hormones, such as melatonin and serotonin. Currently, evidence-based medicine for HH pharmacotherapy is lacking. Acute and prophylactic treatment of HH is based on only a few case reports. Here, we report a case study in which agomelatine showed desirable responsiveness for the prophylactic treatment of HH for the first time. Case description: We present the case of a 58-year-old woman with a 3-year history of nocturnal left temporal pain that awakened her during the wee hours. Brain magnetic resonance imaging did not reveal any midline structural abnormalities associated with circadian rhythms. Polysomnography revealed headache-related awakening at approximately 5:40 am, after the last rapid eye movement phase. No sleep apnea-hypopnea events were observed, without oxygen saturation or blood pressure abnormalities. The patient was prescribed agomelatine 25 mg at bedtime as a prophylactic treatment. In the following month, the frequency and severity of the headaches decreased by 80%. After 3 months, the patient's headache completely resolved, and the medication was discontinued. Conclusion: HH only occurs during sleep in the real world, leading to substantial sleep disturbances in older populations. Headache center neurologists need to focus on the prophylactic treatment of patients before bedtime to avoid nocturnal awakening. Agomelatine is a potential prophylactic treatment option for patients with HH.

Caffeine for Headaches: Helpful or Harmful? A Brief Review of the Literature.

Consumption of caffeine in the diet, both daily and occasional, has a significant biological effect on the nervous system. Caffeine, through various and not yet fully investigated mechanisms, affects headaches. This is especially noticeable in migraine. In other headaches such as hypnic headache, post-dural puncture headache and spontaneous intracranial hypotension, caffeine is an important therapeutic agent. In turn, abrupt discontinuation of chronically used caffeine can cause caffeine-withdrawal headache. Caffeine can both relieve and trigger headaches.

Pediatric hypnic headache: a systematic review.

Introduction: Hypnic headache (HH) is a primary headache, and it is considered a rare condition in children. The underlying mechanisms of HH are not yet fully understood. This systematic review aims to provide a comprehensive description of the clinical features of all published cases of pediatric HH. It will also discuss the differences in headache features between children and adults, the increased diagnostic sensitivity of the new diagnostic criteria (ICHD-3), potential pathophysiological hypotheses explaining the higher incidence in adults, differential diagnoses, and therapeutic options for children. Methods: A systematic search was conducted to identify and analyze articles reporting cases of HH in patients under the age of 18. The search was performed in major medical databases including Cochrane Library, EBSCO, Embase, Medline, PubMed, Science Direct, Scopus, and Web of Science. The search covered the period from 1988 to April 2023. Relevant studies were screened for eligibility, and data extraction was performed using a standardized approach. Results: Seven children with HH were included in the analysis. The mean age of onset for headache attacks was 10 ± 4.3 years (range 3-15 years). The average time from the start of headaches to diagnosis was 15.8 ± 25.0 months (range 1-60 months). Headache features in children differed from those observed in adult HH patients. Children experienced throbbing/pulsating pain, while adults reported dull/pressure-like pain. Children also had lower frequency and shorter duration of attacks compared to adults. The use of ICHD-3 criteria appeared to be more sensitive and inclusive for diagnosing HH in children compared to the previous ICHD-2 criteria. The association of headache attacks with sleep suggests that HH may be a primary disorder with a chronobiological origin. Hypothalamic dysfunction and melatonin dysregulation, which are more prevalent in older individuals, could potentially explain the higher incidence of HH in adults. Other primary headaches and secondary causes should be ruled out. Melatonin prophylactic therapy may be considered for pediatric patients. Discussion: Further evaluation of the clinical features of HH in children is needed. The development of specific diagnostic criteria for pediatric cases could improve diagnostic rates and enhance the management of children with HH.