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Abstract

Background

Hypnic headache is a neurological disorder characterized by recurrent headache attacks that occur exclusively during sleep, leading to awakening. Synthesizing the available epidemiological data might inform clinical decision-making.

Methods

We searched PubMed and Embase for observational studies on hypnic headache published between 1 May 2004, and 22 December 2022. Two investigators independently screened titles, abstracts, and full-text articles. We performed a random-effects meta-analysis with meta-regression to estimate the prevalence of hypnic headache and its clinical features based on epidemiologic data from population-based and clinic-based studies.

Results

Fourteen studies, one population-based and 13 clinic-based, met our eligibility criteria. The population-based study did not identify any people with hypnic headache. From 11 clinic-based studies, the pooled relative frequency of hypnic headache was 0.21% (95%CI, 0.13 to 0.35%; I² = 87%) in adult patients evaluated for headache. The pooled mean age of onset was 60.5 years, with a slight female predisposition. Hypnic headache was typically bilateral (71%), pressing (73%), of moderate (38%) or severe (44%) pain intensity, and lasted about 115 minutes per attack.

Conclusions

Our data should be cautiously interpreted due to between-study heterogeneity. The identified clinical presentation of hypnic headache can guide clinical diagnosis, in addition to the International Classification of Headache Disorders.

Keywords

Primary headache disorders International Classification of Headache Disorders rare headache disorders alarm clock headache

Introduction

Hypnic headache is a rare neurologic disorder that manifests clinically as recurrent attacks of headache developing only during sleep and causing wakening (1). The attacks last up to four hours and unlike trigeminal autonomic cephalalgias are not accompanied by cranial autonomic symptoms or restlessness (1). The disorder was first described in 1988 using the term ‘alarm clock headache’ and was later included in the 2nd edition of the International Classification of Headache Disorders (ICHD) (2).

Most epidemiologic data on hypnic headache come from clinic-based studies and among these reported estimates of its prevalence and clinical features vary considerably (3). This hampers a better understanding of the disorder and might result in misdiagnosis and failure to initiate appropriate treatment. There is therefore a need to provide a synthesis of the available epidemiologic data which, in turn, might facilitate more informed clinical decision-making.

Here, we perform a systematic review and meta-analysis to estimate the prevalence (or relative frequency) of hypnic headache and its clinical features based on epidemiologic data from population-based and clinic-based studies. We also critically appraise the methodologic quality of the studies included and outline directions for future research.

Methods

Search strategy

The present study was registered on PROSPERO (identifier: CRD42022379797) and carried out in accordance with the reporting Guidelines for Meta-Analyses of Observational Studies in Epidemiology (MOOSE) (4). PubMed and Embase were searched from 1 May 2004 to 22 December 2022, for observational studies reporting observational data on hypnic headache. The full search strategy is shown in Supplemental Table 1 (see Online Supplemental Materials). No language restrictions were applied, and reference lists of the originally identified articles were searched to assess whether any additional articles might warrant further review.

Selection criteria

Eligible studies were considered those that included observational data on the prevalence of hypnic headache or its clinical features in the adult general population. We also included studies with observational data on the relative frequency of hypnic headache or its clinical features in adult patients who were evaluated for headache in a clinical setting. The diagnosis of hypnic headache had to be made in accordance with the 2nd or 3rd edition (including beta version) of the International Classification of Headache Disorders (ICHD) (1,2,5) (see Table 1). The full list of inclusion and exclusion criteria are shown in Supplemental Table 3 (see Online Supplemental Materials).

Table 1.

Diagnostic criteria for hypnic headache according to different editions of the International Classification of Headache Disorders.

ICHD-2	ICHD-3β	ICHD-3
A. Dull headache fulfilling criteria B-D B. Develops only during sleep, and awakens patient C. At least two of the following characteristics: 1. Occurs > 15 times per month 2. Lasts ≥ 15 min after waking 3. First occurs after age of 50 years D. No autonomic symptoms and no more than one of nausea, photophobia or phonophobia E. Not attributed to another disorder	A. Recurrent headache attacks fulfilling criteria B-E B. Developing only during sleep, and causing wakening C. Occurs > 10 times per month for > 3 months D. Last ≥ 15 min and up to four hours after waking E. No cranial autonomic symptoms or restlessness F. Not better accounted for by another ICHD-3 diagnosis	A. Recurrent headache attacks fulfilling criteria B-E B. Developing only during sleep, and causing wakening C. Occurring on ≥ 10 days/month for > 3 months D. Lasting from 15 minutes up to 4 hours after waking E. No cranial autonomic symptoms or restlessness F. Not better accounted for by another ICHD-3 diagnosis

ICHD: International Classification of Headache Disorders.

Study selection and data extraction

Two investigators (AGM and AA) independently screened the identified records by title, abstract, and full text. A pre-designed extraction sheet was then used by the two investigators (AGM and AA) to extract data independently. The supplemental material provides a full overview of the data items which were recorded for each study deemed eligible for inclusion (see Online Supplementary Table 4). A third investigator (RHC) was available for assistance if there were any discrepancies during the process of study selection and data extraction.

Risk of bias assessment

The Joanna Briggs Institute Critical Appraisal Instrument for Studies Reporting Prevalence Data was used to evaluate risk of bias (6). Two investigators (AGM and AA) independently carried out the risk of bias assessment for studies reporting on the prevalence (or relative frequency) of hypnic headache. The 9-item instrument has a range of 0 to 100%, with higher scores indicating lower risk of study bias. Studies were then categorized as high risk (≤49%), moderate risk (50%-69%), or low risk (≥70%).

Statistical analysis

Eligible studies were classified as either population-based or clinic-based, and data were analyzed separately for each. The term ‘prevalence’ was used for population-based data, and the term ‘relative frequency’ was used for clinic-based data. The primary outcomes were (I) the prevalence of hypnic headache in population-based studies and (II) the relative frequency of hypnic headache in adults who were evaluated for headache in clinic-based studies. The secondary outcomes were the prevalence of individual clinical features in adults with hypnic headache from population-based samples or the relative frequency of individual clinical features in adults with hypnic headache from clinical samples. Furthermore, the secondary outcomes also included the pooled mean age of onset, duration of attacks, and monthly headache days. A random-effects meta-analysis was performed for each outcome on the condition of their being available data from ≥3 studies with a total sample size of ≥30 participants. The random-effect meta-analysis accounted for between-study heterogeneity, and the inverse variance method or a logistic regression model on logit transformed data was used to calculate pooled estimates. Between-study heterogeneity was assessed using the I² statistics, with values ≥75% indicative of considerable heterogeneity (7). A meta-regression analysis was performed on the primary outcome to discern the factors responsible for heterogeneity amongst the included studies. Adhering to the Cochrane Handbook's guidelines, for every ten studies presenting the same outcome, a single explanatory variable was chosen (7). We conducted two separate meta-regression exploring 1) the ICHD editions as an explanatory variable for heterogeneity, and 2) the impact of prospective vs retrospective case ascertainment on heterogeneity. To identify risk of publication bias, we visualized data with a funnel plot and performed an Egger’s test. All statistical analyses were performed with R version 4.2.0 using “meta”, “metafor” and “metareg” packages.

Results

The database search identified 499 records, of which 362 articles were screened by title and abstract after removal of duplicates. Thirty-three articles were then selected for full-text review (see Figure 1). Of these, 14 studies (one population-based and 13 clinic-based) met the eligibility criteria and were included in the qualitative analysis (i.e., methodologic review) and/or quantitative analysis. The population-based study reported data on the prevalence of hypnic headache in the adult general population but did not provide data on individual clinical features of the disorder (8). Of the 13 included clinic-based studies (9 –21), 11 reported on the relative frequency of hypnic headache in adults who were evaluated for in a tertiary care setting (9 –18,21). Furthermore, six studies provided relative frequencies of individual clinical features of hypnic headache (see Table 2) (11,14,15,18 –20). Notably, ten of 14 studies recorded data retrospectively (9,11,14,15,17 –21 ), and the remaining four studies did so prospectively (10,12,13,16). The ICHD criteria for hypnic headache were applied by all included studies, with nine using the ICHD-2 criteria (10 –16,19,20) and five using the ICHD-3β or ICHD-3 criteria (8,9,17,18,21).

Figure 1.

Flow diagram.

Table 2.

Characteristics of the included studies reporting on the prevalence or relative frequency of hypnic headache and its clinical features.

Author	Year	Journal	ICHD Version	Setting	Parti-cipants	Participants with HH, n (%)	Monthly Headache Days, mean (SD)	Usage
Eliasson et al.	2020	Cephalalgia	ICHD-3	Population-based	921	0 (0%)	Not reported	Prevalence
Lupi et al.	2018	Cephalalgia	ICHD-3	Clinic-based	20083	31 (0.15%)	Not reported	Relative frequency
Rammo-han et al.	2021	Neurology India	ICHD-2/ICHD-3β	Clinic-based	14562	11 (0.07%)	20.36 (11.67)	Relative frequency and clinical characteristics
Silva-Néto et al.	2014	Neurological Sciences	ICHD-2	Clinic-based	11360	25 (0.22%)	Not reported	Relative frequency and clinical characteristics
Liang et al.	2008	Cephalalgia	ICHD-2	Clinic-based	6106	17 (0.28%)	Not reported	Relative frequency and clinical characteristics
Carvalho Felicio et al.	2006	Arq Neuropsiquiatr.	ICHD-2	Clinic-based	3328	24 (0.72%)	Not reported	Relative frequency and clinical characteristics
Ruiz et al.	2013	Neurologia	ICHD-2	Clinic-based	1868	6 (0.32%)	Not reported	Relative frequency
Song et al.	2016	Journal of Clinical Neurology	ICHD-3β	Clinic-based	1627	1 (0.06%)	Not reported	Relative frequency
Mulero et al.	2012	Neurologia	ICHD-2	Clinic-based	1180	13 (1.1%)	14.5 (7.6)	Relative frequency
Zanchin et al.	2005	The Journal of Headache and Pain	ICHD-2	Clinic-based	775	3 (0.4%)	Not reported	Relative frequency
Ramón et al.	2013	European Neurology	ICHD-2	Clinic-based	528	1 (0.19%)	Not reported	Relative frequency
Lobo et al.	2022	Cephalalgia	ICHD-3	Clinic-based	162	1 (0.6%)	Not reported	Relative frequency
Holle et al.	2011	Cephalalgia	ICHD-2	Clinic-based	30	15 (50%)	23	Clinical features
Manni et al.	2004	Neurology	ICHD-2	Clinic-based	10	10 (100%)	Not reported	Clinical features

ICHD: International Classification of Headache Disorder, HH: hypnic headache, SD: standard derivation.

Prevalence and relative frequency of hypnic headache

The prevalence of hypnic headache was evaluated in one Icelandic population-based study (8), in which 921 adults aged 20 to 69 years were enrolled from the general population. The participants had been identified using national registries and cancer screening programs. The authors found that none met the ICHD-3β criteria for hypnic headache, whilst two (0.2%) of 921 participants had probable hypnic headache.

Eleven clinic-based studies, comprising a total of 110 patients, reported on the relative frequency of hypnic headache among adults who were evaluated for headache in a tertiary care setting (see Table 2). The pooled relative frequency of hypnic headache was found to be 0.21% (95% CI, 0.13 to 0.35%; I² = 86%) (see Figure 2) (9 –18,21). Visual inspection of the funnel plot indicated slight asymmetry, however, Egger’s test for asymmetry was negative (P = 0.8232) (see Figure 3).

Figure 2.

Forest plot of relative frequencies of hypnic headache in clinic-based studies.

Figure 3.

Funnel plot of relative frequencies of hypnic headache in clinic-based studies.

The meta-regression found a difference between studies applying ICHD-3 and ICHD-2 criteria (P < .001). The relative frequency of hypnic headache in studies applying ICHD-3 was decreased by a factor of 1.46. The heterogeneity can partly be attributed to the differences in ICHD iterations as this accounted for 43.4% of the heterogeneity. In meta-regression, the use of retrospective vs prospective data acquisition did not affect the heterogeneity (estimate -0.22, P = 0.71) (Online Supplemental Table 6).

Relative frequency of individual clinical features

Six clinic-based studies, comprising a total of 97 patients, provided data on the relative frequency of individual clinical features of hypnic headache (12 –14,17 –19). The mean age of disease onset was 60.5 years (95% CI, 54 to 67 years; I² = 86%), and 57% were females (95% CI, 42 to 70%; I² = 52%). The mean number of monthly attacks was 20 (95% CI, 16 to 25 attacks per month; I² = 51%), and the mean duration of each attack was 115 minutes (95% CI, 85 to 146 minutes; I² = 0%). Most attacks occurred at night (94%; 95% CI, 58 to 100%; I² = 20%) and were of bilateral location (71%; 95% CI, 60 to 80%; I² = 4%), pressing quality (73%; 95% CI, 44 to 90%; I² = 65%), and moderate (38%; 95% CI, 20% to 61%) or severe pain intensity (44%; 95% CI, 29% to 61%; I² = 59%). Accompanying symptoms to headache were phonophobia (20%; 95% CI, 12 to 32%; I² = 39%), photophobia (12%; 95% CI, 5 to 29%; I² = 0%), and nausea (14%; 95% CI, 7 to 27%; I² = 0%). Moreover, co-existing migraine was present in 25% of patients with hypnic headache (95% CI, 15 to 28%; I² = 12%), as determined from four studies (14,18 –20). Data on comorbid tension-type headache (TTH) was limited to one study, revealing that three of 11 patients experienced both disorders (18) (see Table 3).

Table 3.

Demographic and clinical characteristics of patients with hypnic headache.

Characteristics	Pooled Relative Frequency or Pooled Mean (CI 95%)	Heterogeneity, $I^{2}$ (CI 95%)	No. of Studies	No. of Patients with HH
Age of onset, years	60.5 (53.9; 67.1)	85.5% (68.0%; 93.4%)	5	86
Female, %	56.5 (41.8; 70.2)	51.7% (0.0%; 80.7%)	6	97
Frequency, attacks/month	20.3 (16.1; 24.5)	50.5% (0.0%; 85.7%)	3	45
Duration, minutes	115.4 (85.1; 145.8)	0.0%	2	26
Nocturnal, %	94.0 (57.8; 99.5)	20.4% (0.05; 65.0%)	6	97
Laterality, %
Unilateral	29.3 (20.5; 40)	3.7% (0.0%; 80.0%)	5	82
Bilateral	70.7 (60.0; 79.5)	3.7% (0.0%; 80.0%)	5	82
Pain intensity, %
Mild	5.8 (1.8; 16.5)	0.0% (0.0%; 74.6%)	6	97
Moderate	38 (19.6; 60.6)	66.1% (18.8%; 85.8%)	6	97
Severe	44 (28.6; 60.1)	59.2% (0.0%; 83.4%)	6	97
Pain quality, %
Stabbing	7.91 (2.0; 26.4)	0.0% (0.0%; 79.2%)	5	82
Pulsating	14.4 (6.5; 29.1)	45.0% (0.0%; 79.8%)	4	82
Pressing	72.5 (44.3; 89.7)	65.4% (17.0%; 85.6%)	6	97
Burning	1.5 (0.0; 10.0)	0.0% (0.0%; 84.7%)	4	65
Migraine-like features, %
Nausea	14.0 (6.6; 27.2)	0.0% (0.0%; 74.6%)	6	97
Photophobia	12.2 (4.6; 28.5)	0.0% (0.0%; 74.6%)	6	97
Phonophobia	20.0 (11.6; 32.4)	38.7% (0.0%; 75.7%)	6	97
Vomiting	0.0 (0.0; 100)	0.0% (0.0%; 79.2%)	5	72
Co-existing headache disorders, %
Migraine	25 (15;38)	12% (0.0%; 86.5%)	4	53

CI: confidence interval, HH: hypnic headache, No.: number.

Risk of bias

We assessed risk of bias in the 11 clinic-based studies that reported on the relative frequency of hypnic headache in adults who were evaluated for headache (9 –18,21). Three studies had a moderate risk of bias (10,12,18), and eight studies had a high risk of bias (9,11,13 –17,21). All eleven studies failed to include an appropriate sample size and report a response rate. Most did not provide adequate information on subject selection and study setting. The risk of bias assessment is summarized in Supplementary Tables 2 and 5 (see Online Supplemental Materials).

Discussion

The results of our meta-analysis showed that the pooled relative frequency of hypnic headache was 0.21%, which corresponds to about one in every 450 patients who are evaluated for headache in tertiary care units. However, this pooled relative frequency was associated with considerable heterogeneity between the studies. Furthermore, the pooled relative frequency should be interpreted with caution given the studies’ poor quality and moderate to high risk of bias.

In the only population-based study (8), the prevalence of hypnic headache was 0.0% in 921 people, which highlights the challenges of investigating rare disorders in the general population.

Clinical characteristics

Our analysis revealed a distinct clinical phenotype of hypnic headache that may aid in its diagnosis beyond being strictly a sleep-related headache. Typically, hypnic headache presents around the age of 60.5 years, with a slight female predisposition. The headache is predominantly bilateral, pressing, and of moderate-to-severe pain intensity, lasting approximately two hours. Nausea (14%), photophobia (12%), and phonophobia (20%) were relatively infrequent accompanying symptoms, and no participants reported vomiting in any of the multiple studies analyzed. While this phenotype shares many similarities with that described in the ICHD-3 criteria, we observed two important distinctions. Specifically, we found that pain intensity was predominantly moderate-to-severe, and onset occurred around the age of 60 years, whereas in the ICHD-3 comments, pain intensity was typically described as mild to moderate, and onset occurred after the age of 50 years (1).

Methodological considerations

The considerable between-study heterogeneity in the pooled relative frequency of hypnic headache can be explained by several factors. First, the clinic-based studies used different ICHD criteria, with two studies using ICHD-3 (9,17), nine using ICHD-2 (10 –16,19,20), one using ICHD-3B (21) and one using a combination of ICHD-2 and ICHD-3β (18). The 2nd and 3rd editions of the ICHD differ in several respects (1,2). ICHD-3 has a few criteria that are more inclusive, as they allow for patients to experience a lower frequency of headaches per month (≥10 days/month vs ≥15), do not specify an age of onset, and allow for patients to report more than one of nausea, phonophobia, or photophobia (1). However, ICHD-3 is more exclusive in other regards, as it limits the duration of headache to four hours (1). This might enable ICHD-3 to better distinguish migraine from hypnic headache, as ICHD-2 allows patients to have prolonged headache (≥ 4 hours) with accompanying nausea (1,2). ICHD-2, therefore, overlaps with the diagnostic criteria for migraine, potentially explaining why the relative frequency was seemingly higher in studies applying ICHD-2. To investigate this, we conducted a meta-regression, which confirmed that studies using ICHD-2 criteria had a higher relative frequency of hypnic headache.

Most individual clinical features of hypnic headache demonstrated low heterogeneity, indicating their reliability as potential indicators for the disorder. However, some features such as age of onset, female gender, moderate and severe pain intensity, and a pressing character exhibited substantial heterogeneity, with values exceeding 50%. The observed heterogeneity could be due to various factors, such as differences in study design, sample characteristics, or diagnostic criteria. It is worth noting that the meta-analyses were based on small sample sizes, which increases the risk of bias in the I² statistic (22). Therefore, caution is advised when interpreting the between-study heterogeneity of the clinical features. Further studies with larger sample sizes are needed to ascertain the clinical presentation of hypnic headache.

An important observation is the paucity of data on hypnic headache and the presence of comorbid disorders, including other headache disorders. This is evident from the limited number of studies that have reported on the co-existence of hypnic headache with migraine and TTH. Given these glaring gaps, it is imperative for future research to delve into the co-existence of hypnic headache with other disorders. Such studies might not only assist in formulating a hypothesis on the neurobiologic underpinnings of hypnic headache but also provide a more comprehensive clinical picture, aiding in its diagnosis and management.

Differential diagnoses

To diagnose hypnic headache, it is necessary to differentiate it from other primary headache disorders such as migraine, tension-type headache (TTH), and cluster headache (1). This can be achieved through a comprehensive medical history, as the clinical examination is expected to be normal for all of these disorders. It is important for clinicians to be aware that some patients might have hypnic headache in addition to comorbid migraine, for instance.

Hypnic headache can be differentiated from migraine based on its strictly sleep-related presentation and the absence of accompanying symptoms such as nausea, vomiting, phonophobia, and photophobia, which are very commonly experienced during migraine attacks (23). Additionally, while migraine headaches are usually pulsating and unilateral, hypnic headaches are typically pressing and bilateral. There is also no reported data on hypnic headache, unlike migraine, being aggravated by routine physical activity. Furthermore, hypnic headache typically presents in individuals aged about 60.5 years, while migraine usually develops during adolescence or early adulthood (24). However, since migraine can be life-long, it is important to inquire about the age of onset to assess potential overlap between the two disorders, although data on this is scarce and requires further research.

Another differential diagnosis for hypnic headache is TTH, albeit clinical experience tells us that it is rare for patients with TTH to complain of headache causing awakening. Like hypnic headache, TTH often presents with bilateral and pressing pain (25). However, the duration of TTH can last from 30 minutes to seven days with a mild-to-moderate intensity, while the duration of hypnic headache is estimated to be 115 minutes and of moderate or severe pain intensity. Nonetheless, there might be some overlap in the intensity and duration, even if hypnic headache is generally more severe and shorter-lasting than TTH.

A less common differential diagnosis is cluster headache, which has an estimated prevalence of 0.1% in the general population (26). Like hypnic headache, cluster headache can occur at night (27), making it challenging to distinguish between the two disorders. Restlessness during some cluster headache attacks might resemble the motor activity reported in one study of patients with hypnic headache (18). However, motor activity in hypnic headache is less prominent and consists of aimless activities such as eating or watching television (18). Cranial autonomic symptoms and attack clustering are also distinguishing factors that exclude the diagnosis of hypnic headache. In addition, patients with cluster headache usually experience severe or very severe unilateral attacks (27), while hypnic headache typically presents as moderate or severe bilateral headaches. Our meta-analysis also found a slight female preponderance for hypnic headache, which differs from the 2.5:1 male-to-female ratio reported in cluster headache (28).

Future directions

Estimating the true prevalence of hypnic headache is challenging because almost all studies are based on clinical samples. Population-based studies adhering strictly to the ICHD criteria provide a more accurate estimate of the true prevalence. However, the sample size required for such studies will be in the tens of thousands to obtain robust estimates. This makes population-based studies less feasible and highlights the challenges of investigating hypnic headache in the general population.

Instead of relying solely on population-based studies, future research can improve estimates of the relative frequencies of hypnic headache in clinic-based settings by implementing certain changes. Clinicians should consider that hypnic headache typically debuts at a later age and exhibits circadian variation, which fulfills the red flags that necessitate neuroimaging to exclude secondary headache disorders (29). Furthermore, hypnic headache is an exclusion diagnosis, and it is essential to rigorously rule out other possible headache disorders. In this regard, investigators should report the duration and characteristics of untreated headache attacks to exclude headache attacks of longer duration, as seen with migraine and TTH (1). Future studies should also report the age of onset, headache characteristics, motor activity, and aggravation from physical activity to improve the clinical characterization of hypnic headache. In addition, research is needed to ascertain the likely association of hypnic headache with poor sleep quality, given that headache on average caused awakening 20 times per month. This will require the use of sleep diaries or objective measures of sleep quality. Such evidence can, in turn, improve our understanding of hypnic headache and lead to better diagnosis and treatment.

An optimal treatment strategy for hypnic headache has yet to be established. Reported options include caffeine, lithium, and indomethacin, albeit the scientific evidence for using these treatments is very limited. It remains unclear whether hypnic headache responds to standard treatments for tension-type headache, migraine, or cluster headache. Therefore, interventional studies with well-defined outcomes are necessary to determine the most efficacious treatment for hypnic headache.

Limitations

This meta-analysis has several limitations. The included studies used various editions of the ICHD criteria, and the meta-regression analysis indicated that studies using ICHD-3 criteria reported lower relative frequencies of hypnic headache than those using ICHD-2.Moreover, case reports and studies with fewer than 10 participants were excluded to avoid overrepresentation of highly selected cases that might bias the results. Another concern is publication bias, as investigators who fail to identify cases with hypnic headache might not publish their findings. A funnel plot showed some asymmetry, indicating a possible publication bias in the form of a small study effect. However, the subsequent Egger’s test did not detect publication bias, although this test might be underpowered in small meta-analyses (30).

Conclusions

Our meta-analysis showed that hypnic headache was found in about 0.21% in patients who were evaluated for headache in tertiary care units. However, caution is necessary when interpreting the relative frequency due to considerable between-study heterogeneity and methodological limitations. In terms of clinical characteristics, our analysis found that patients with hypnic headache typically presented with moderate or severe, pressing, and bilateral headaches.

Key findings

The relative frequency of hypnic headache was found to be 0.21% of patients who were evaluated for headache in tertiary care units.

Hypnic headache typically presents as a sleep-awakening, moderate or severe, pressing, and bilateral headache. Patients were typically older with a mean of 60.5 years of age.

Estimates of prevalence and relative frequency are challenging to establish due to a general lack of reliable and robust epidemiological data.

Declarations of conflicting interest

The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: HMA reports personal fees from Pfizer, outside of the submitted work. FMA has received personal fees from Pfizer, Teva, Lundbeck, Novartis, and Eli Lilly, outside of the submitted work. FMA serves as an Associate Editor for Frontiers in Neurology, Frontiers in Pain Research, Acta Neurologica Scandinavica, and Headache Medicine. FMA is also President of the Danish Headache Society and serves on the Board of Directors of the European Headache Federation. HA reports personal fees from Lundbeck and Teva, outside of the submitted work. AGM, AA, and RHC declare no potential conflicts of interest.

Supplemental Material

sj-pdf-1-cep-10.1177_03331024231218389 - Supplemental material for Epidemiology and clinical features of hypnic headache: A systematic review and meta-analysis

Supplemental material, sj-pdf-1-cep-10.1177_03331024231218389 for Epidemiology and clinical features of hypnic headache: A systematic review and meta-analysis by Anna G. Melchior, Amenah Ayyoub, Rune Häckert Christensen, Haidar Muhsen Al-Khazali, Faisal Mohammad Amin and Håkan Ashina in Cephalalgia

Footnotes

Author contributions

HMA, RHC and HA conceived and designed (including search strategies) the review. AGM and AA performed the literature search. AGM wrote first and subsequent manuscript drafts. HA, RHC, HMA, FMA, and AA critically revised and reviewed the article for intellectual content. All authors approved the final version.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Håkan Ashina

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