Headache in sleep apnea syndrome: Epidemiology and pathophysiology

Abstract

This review investigates the relation between obstructive sleep apnea and sleep apnea headache, migraine and tension-type headache. Focus is made on studies from the general population with interviews conducted by a physician and obstructive sleep apnea confirmed by polysomnography.

Obstructive sleep apnea syndrome is observed in 3% of the middle-aged population. The prevalence of sleep apnea headache in this population is 12%–18%, while morning headache with similar symptomatology as sleep apnea headache occur in 5%–8% of the general population. People with sleep apnea headache did have significantly more minutes below 90% oxygen saturation (23.1 min vs. 1.9 min, p = 0.002), higher level of average oxygen desaturation (5.9% vs. 4.5%, p < 0.001) and lower average of the lowest oxygen saturation (80.9% vs. 88.5%, p < 0.001) than people with morning headache. A comparison of those with obstructive sleep apnea with or without sleep apnea headache showed no significant differences. Thus, oxygen desaturation alone cannot explain the pathophysiology of sleep apnea headache.

Obstructive sleep apnea and migraine, and obstructive sleep apnea and tension-type headache are not related in the general population.

The cause of sleep apnea headache remains to be elucidated.

Introduction

Hypnic headache is defined as one that awakens one during night (1). The only other primary headache that awakes one during night is cluster headache. If migraine and/or tension-type headache develops during the night the patient wakes up with that headache in the morning. Sleep apnea headache is characterized by morning headache thought to be secondary to obstructive sleep apnea (1).

The present review investigates the relation between obstructive sleep apnea and sleep apnea headache, morning headache, migraine and tension-type headache as well as the epidemiology and pathophysiology of sleep apnea headache. Focus is placed on studies from the general population with clinical interviews and examination by a physician, and obstructive sleep apnea documented by polysomnography. These preferences were made in order to minimize biases as questionnaires and lay interviews are usually less precise than an interview by a physician, and self-reports of sleep pattern are less precise than polysomnography in relation to obstructive sleep apnea.

Search strategy

PubMed was searched using the phrases “sleep apnea and headache and population” and “sleep apnea and migraine and population.” This search was supplemented with papers from the authors’ files.

Obstructive sleep apnea

Obstructive sleep apnea is characterized by partly or complete obstruction of the upper airways during sleep causing repeated airflow cessation (hypopnea and/or apnea), oxygen desaturation and sleep disruption. The sleep disruption does not fully awaken the person.

Obstructive sleep apnea is defined by an apnea hypopnea index (AHI) of ≥ 5 based on the polysomnography recording. It is calculated by dividing the number of apneic events by the number of hours of sleep. It is subdivided into mild (5≤ and <15 per hour), moderate (15≤ and <30 per hour) and severe (30 ≤ per hour) sleep apnea depending on the frequency. The majority have only minor symptoms and signs in addition to snoring, hypopnea and apnea. However, if the obstructive sleep apnea causes daytime fatigue, excessive daytime sleepiness, or reduced cognitive function due to unrefreshed sleep, it is called obstructive sleep apnea syndrome.

Obstructive sleep apnea is associated with obesity, i.e. high body mass index (BMI) in adults, and is associated with obesity and/or adenotonsillar hypertrophy in children, as the influence of adenoid size decreases in adolescents (2).

Obstructive sleep apnea may also appear for only a short period of time, for instance, during upper respiratory infection with or without adenotonsillar hypertrophy or under the influence of alcohol, benzoediazepines, morphinomimetics and other drugs that relax body tone and/or interfere normal arousal.

Prevalence of obstructive sleep apnea

Obstructive sleep apnea is very common: The prevalence is 20% in middle-aged adults from the general population, i.e. one of every five people (3–5). The prevalence is less in children and the elderly. Although obstructive sleep apnea syndrome is less common than obstructive sleep apnea, it is still a prevalent disorder among middle-aged adults, with an estimated prevalence of 3% in the general population, with men affected twice as often as women (3,6).

Definition of sleep apnea headache and morning headache

Sleep apnea headache is usually a universal morning headache of less than four hours’ duration caused by sleep apnea. The International Classification of Headache Disorders (ICHD), third edition (beta) diagnostic criteria are shown in Table 1 (1). The sleep apnea headache should have a causal relation to sleep apnea, while the frequency and specific headache characteristics are not mandatory for the diagnosis. The sleep apnea headache should recur >15 days/month, while headache characteristics are those of tension-type headache in relation to pain location and quality, and accompanying symptoms are not allowed.

Table 1.

The International Classification of Headache Disorders III β (ICHD-3 beta) diagnostic criteria for sleep apnea headache.

A. Headache present on awakening after sleep and fulfilling criterion C

B. Sleep apnea (apnea-hypopnea index ≥ 5) has been diagnoseda

C. Evidence of causation demonstrated by at least two of the following:

1. headache has developed in temporal relation to the onset of sleep apnea

2. either or both of the following:

a) headache has worsened in parallel with worsening of sleep apnea

b) headache has significantly improved or remitted in parallel with improvement in or resolution of sleep apnea

3. headache has at least one of the following three characteristics:

a) recurs on >15 days per month

b) all of the following:

(i) bilateral location

(ii) pressing quality

(iii) not accompanied by nausea, photophobia or phonophobia

c) resolves within four hours

D. Not better accounted for by another ICHD-3 diagnosis.

^aThe apnea-hypopnea index is calculated by dividing the number of apneic events by the number of hours of sleep (5–15/hours = mild; 15–30/hours = moderate; >30/hours = severe).

Morning headache is similar to that of sleep apnea headache, but it is not caused by obstructive sleep apnea.

The prevalence of sleep apnea headache and morning headache

A large Swedish cross-sectional study of people suffering from snoring and obstructive sleep apnea syndrome found that 18% experienced headache often or very often upon awakening, i.e. sleep apnea headache, while only 5% of the general population experienced the same type of headache (7). Thus, snoring and obstructive sleep apnea syndrome increase the risk of sleep apnea headache three- to four-fold.

A study of the general population of Germany, Italy, Portugal, Spain and the United Kingdom based on a structured telephone lay interviewer found that chronic morning headache was experienced by 7.6% of the participants, while 15.2% of those with breathing-related sleep disorders had chronic morning headache (8).

A Norwegian epidemiological survey of the general population based on polysomnography and an interview and examination by a physician found that 11.8% of the participants with obstructive sleep apnea had sleep apnea headache, while 4.6% of those without obstructive sleep apnea had morning headache with similar symptomatology as sleep apnea headache (9).

When using the cutoff of moderate (AHI ≥ 15) and severe (AHI ≥ 30) obstructive sleep apnea, the prevalence of sleep apnea headache was 11.6% (n = 19) and 13.3% (n = 11), respectively.

Obstructive sleep apnea and migraine in the general population

A Norwegian epidemiological survey of the general population investigated the association of obstructive sleep apnea and migraine. The participants underwent a clinical interview, a physical and a neurological examination by physicians, as well as in-hospital polysomnography (10). Migraine without aura and migraine with aura were diagnosed according to the ICHD, second edition (11). The prevalence of migraine without aura was 12.5% and that of migraine with aura was 6.8% among those with obstructive sleep apnea. The logistic regression analyses disclosed no relationship between migraine without aura and obstructive sleep apnea, or migraine with aura and obstructive sleep apnea. The adjusted odds ratio was 1.15 (95% confidence interval (CI) 0.65–2.06) for migraine without aura, and 1.15 (95% CI 0.95–2.39) for migraine with aura. The result did not change using a cutoff of moderate (AHI ≥ 15) and severe (AHI ≥ 30) obstructive sleep apnea. Thus, neither migraine without aura nor migraine with aura are related to obstructive sleep apnea in the general population (10).

Obstructive sleep apnea and tension-type headache in the general population

A Norwegian study compared the prevalence of headache in a clinic population referred for suspected sleep apnea syndrome and the general population (12). The clinic population completed a questionnaire about sleep and headache. Headache was more likely among patients admitted for polysomnography compared with the general population. In the multivariate analyses, this association was mainly restricted to those with complaints ≥7 days/months. Chronic headache (≥15 days/month) was seven times more common in those referred for suspected sleep apnea than in the general population.

There was no linear dose-response relationship between headache and severity of apnea.

Another Norwegian epidemiological survey investigated the relationship between tension-type headache and obstructive sleep apnea in the general population. The participants underwent a clinical interview, a physical and a neurological examination by physicians, as well as in-hospital polysomnography (13). Tension-type headache was diagnosed according to the ICHD, second edition (11). The prevalence of frequent tension type headache was 18.7%, and that of chronic tension-type headache was 2.1% in those with obstructive sleep apnea. The logistic regression analyses disclosed no significant relationship between tension-type headache and obstructive sleep apnea. The adjusted odds ratios was 0.95 (95% CI 0.55–1.62) for frequent tension-type headache, and was 1.91 (95% CI 0.37–9.85) for chronic tension-type headache. The result did not change using a cutoff of moderate (AHI ≥ 15) and severe (AHI ≥ 30) obstructive sleep apnea. Thus, the presence and severity of sleep apnea does not influence presence and frequency of tension-type headache in the general population.

Pathophysiology of sleep apnea headache and obstructive sleep apnea

The specific pathophysiology of sleep apnea headache is not precisely known. The ICHD-III beta added the following comment to the diagnostic criteria of sleep apnea headache (1): “Although morning headache is significantly more common in patients with sleep apnea than in the general population, headache present on awakening is a non-specific symptom which occurs in a variety of primary and secondary headache disorders, in sleep-related respiratory disorders other than sleep apnea (e.g. Pickwickian syndrome, chronic obstructive pulmonary disorder), and in other primary sleep disorders such as periodic leg movements of sleep. It is unclear whether the mechanism of 10.1.4 Sleep apnea headache is related to hypoxia, hypercapnia or disturbance in sleep.”

A Norwegian epidemiological survey of the general population found that excessive daytime sleepiness was equally frequent in those with sleep apnea headache and morning headache (54.3% vs. 54.5%) (9). Similarly there were no significant differences regarding total sleep time and average oxygen saturation, but those with sleep apnea headache did have significantly more minutes below 90% oxygen saturation (23.1 minutes vs. 1.9 minutes, p = 0.002), higher level of average oxygen desaturation (5.9% vs. 4.5%, p < 0.001) and lower average of the lowest oxygen saturation (80.9% vs. 88.5%, p < 0.001) as compared with participants with morning headache (9).

A comparison of those with obstructive sleep apnea with or without sleep apnea headache did not reveal significant differences in total sleep time, average oxygen saturation, minutes below 90% oxygen saturation (23.1 minutes vs. 22.4 minutes, p = 0.517), higher level of average oxygen desaturation (5.9% vs. 5.8%, p = 0.749) or lower average of the lowest oxygen saturation (80.9% vs. 81.8%, p = 0.571). Thus, oxygen desaturation alone cannot explain the pathophysiology of sleep apnea headache.

Pathophysiology of migraine/tension-type headache and obstructive sleep apnea

There is no causal relation between migraine and obstructive sleep apnea or between tension-type headache and sleep apnea (10,13). Thus, there is no pathophysiological link between migraine/tension-type headache and obstructive sleep apnea.