Department of Neurology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Obstructive sleep apnea syndrome (OSAS) is a common disorder characterized by recurrent apnea during sleep. Nocturnal laboratory-based polysomnography (PSG) is the gold standard test for diagnosis of OSA. The sufferers may complain from daytime sleepiness, snoring or occasional headaches. Serious consequences such as cardiovascular complications, stroke or symptoms of depression may complicate the syndrome. Headache prevalence due to sleep apnea is estimated 1%-2% in general population and affects 2%-8% of middle age population. Morning headache is more common in the OSAS patients. OSAS patients present with various characteristics of morning headache. Treatment with continuous positive airway pressure usually reduces headache. The pathophysiologic background for a relation between obstructive sleep apnea and morning headache is multifactorial. Some theories have been proposed for OSAS-related headaches such as changing oxygen saturation during sleep, cerebral vasodilation and increased intracranial pressure due to cerebral vasodilation, sleep disruption and depression but the definite cause of headaches in OSAS patients is not yet clear.
Introduction Obstructive sleep apnea syndrome (OSAS) is a relatively common disorder characterized by recurrent episodes of apnea or hypopnea for at least 10 seconds during sleep. The term apnea means the complete pause of airflow. Hypopnea is referred to the partial airflow pause terminated in oxygen desaturation or arousal. As a consequence, sleep disruption and daytime sleepiness constitute the main clinical features. Snoring is also common among patients with OSAS and occurs due to increased resistance in the pharyngeal airflow pathway. Association between OSAS and various chronic conditions has been proved. Obesity, cognitive disorders, cardiovascular diseases, chronic obstructive pulmonary disease (COPD), hypertension, glucose intolerance and psychological disorders such as depression and anxiety are some of these diseases (1,2). The disease definition and its severity are ascertained by the apnea–hypopnea index (AHI), which is defined as apneas and/or hypopneas per hour of sleep (1). OSAS refers to AHI equal or more than 5/hour. The American Academy of Sleep Medicine (AASM) classified OSAS severity based on AHI and the degree of sleepiness (Table 1) (3).
Obesity leads to upper airway narrowing by mechanical pressure or structural changes. Several studies show that OSAS is a state of oxidative stress. Free radical production (especially superoxide) in OSAS intensifies atherosclerosis and endothelial damage (4). The treatment of choice in severe sleep apnea is continuous positive airway pressure (CPAP) (1). While this potentially life-threatening condition is common, many of the patients remain unrecognized (5). Thus, updating the knowledge about various clinical features of this syndrome is of great value. This article aims to review the studies regarding headache as one of the clinical presentation of OSAS.
Sleep apnea and headaches Previous studies showed a strong association between sleep apnea and headache and there is growing evidence about hypothalamus involvement in this disorder. In 1970, a relationship has been described between sleep stage and headache (6). Some types of headache are present during rapid eye movement (REM) sleep. Locus ceruleus, periaqueductal gray matter (PAG) and dorsal raphe nucleus function reduce during REM and they might be the fundamental causes of headaches (7). These headaches divide into two classes including the first group with headaches correlated with OSAS and the second group consists of headaches associated with insomnia (8). Initially, it is crucial to rule out secondary headaches. International headache society (IHS) defined OSAS headaches as a compressive pain occurred on awaking, without nausea, photophobia and phonophobia, accompanied by AHI more than 5 (9). Sleep apnea headache prevalence is estimated 1%-2% in general population and 2% -8% in middle age (10). Recently, polysomnography findings improve our knowledge about sleep related headaches. Various pathophysiological theories have been proposed for sleep apnea headaches such as changing in oxygen saturation during sleep, cerebral vasodilation, increased intracranial pressure (ICP), sleep fragmentation or depression. However, the exact cause of this type of headache still remains unclear (11).
Literature review Headaches are reported in at least 50 percent of OSAS sufferers (10) and may be the main complaint (12). Moreover, previous studies showed that morning headache was more common in habitual snorers (13). IHS classifies obstructive sleep apnea (OSA) headaches under the subgroup of “headache attributed to hypoxia and/or hypercapnia” (9). There are articles that show the role of intermittent hypoxia in pathophysiology of OSA headaches (14,15); however, the recent studies have made a question regarding such a relationship (10,12,15). Sleep fragmentation due to frequent apneas and arousals has been suggested as a cause of headaches (8). Furthermore, further investigation failed to show a significant difference between OSA patients with and without headaches regarding sleep efficiency (12,15) or a relationship between OSA severity and headaches (16-18). There is evidence that anxiety and depression are more common in patients with OSAS (19). Depression prevalence in OSAS population has been reported between 7% and 56% and higher depression score is associated with severe OSAS (4). While these patients take several medications for their psychological problems, they would benefit from sleep management policies (20). Therefore, headaches in OSAS patients may be attributed to simultaneous coincidence depression or anxiety disorders (12). According to IHS criteria, appropriate treatment of OSAS relieves OSA headaches (8). Several studies showed that the CPAP usage, the treatment of choice for OSAS, for a month could treat sleep apnea headaches (8,16).
Conclusion There is a strong link between morning headaches and OSAS. Although several mechanisms have been suggested as the pathophysiology, the definite cause of headaches in OSAS patients is not yet clear. Investigation for the existence of sleep apnea is recommended for individuals with morning headaches, especially in the presence of snoring, daytime sleepiness, hypertension or high BMI.
Acknowledgement We would like to thank Clinical Research Development Unit of Ghaem Hospital for their assistant in this manuscript.
Conflict of Interest The authors declare no conflict of interest.
Ho ML, Brass SD. Obstructive sleep apnea. Neurol Int. 2011;3:e15.
Rezaeetalab F, Rezaeitalab F, Dehestani V. Inhaled steroids reduce apnea-hypopnea index in overlap syndrome. Pneumologia. 2013;62:212-214.
American Academy of Sleep Medicine. International classification of sleep disorders: diagnostic and coding manual. 2nd ed. Darien: Amer Academy of Sleep Medicine; 2005.
Franco CM, Lima AM, Ataíde L Jr, et al. Obstructive sleep apnea severity correlates with cellular and plasma oxidative stress parameters and affective symptoms. J Mol Neurosci. 2012;47:300-310.
Fishman AP, Elias JA, Grripi MA, et al. Fishman’s pulmonary diseases and disorders. 4th ed. USA: McGraw-Hill; 2008.
Dexter JD, Weitzman ED. The relationship of nocturnal headaches to sleep stage patterns. Neurology. 1970;20:513-518.
Evers S, Barth B, Frese A, et al. Sleep apnea in patients with cluster headache: a case-control study. Cephalalgia. 2014;34:828-832.
Singh NN, Sahota P. Sleep-related headache and its management. Curr Treat Options Neurol. 2013;15:704-722.
IHS classification ICHD-II. 2013 May. Available from: http://ihs-classification.org/en.
Russell MB. Sleep apnea headache: a growing concern in an increasingly obese population? Expert Rev Neurother. 2013;13:1129-1133.
Evers S, Barth B, Frese A, et al. Sleep apnea in patients with cluster headache: a case-control study. Cephalalgia. 2014 ;34:828-832.
Rezaitalab F, Froughipour M, Sasannejad P, et al. The association of headaches with obstructive sleep apnea syndrome diagnose at the sleep laboratory of Ebn-e-Sina hospital in Mashhad. Medical Journal of Mashhad University of Medical Science. 2014;56:323-329.
Chen PK, Fuh JL, Lane HY, et al. Morning headache in habitual snorers: frequency, characteristics, predictors and impacts. Cephalalgia. 2011;31:829-836.
Greenough GP, Nowell PD, Sateia MJ. Headche complaints in relation to nocturnal oxygen saturation among patients withsleep apnea syndrome. Sleep Med. 2002; 3: 361-364.
Goder R, Friege L, Fritzer G, et al. Morning hradache in patients with sleep disorders: a systemic polysomnographic study. Sleep Med. 2003; 4: 385-391.
Johnson KG, Ziemba AM, Garb JL. Improvement in headaches with continuous positive airway pressure for obstructive sleep apnea: a retrospective analysis. Headache. 2013;53:333-343.
Kristiansen HA, Kværner KJ, Akre H, et al. Sleep apnoea headache in the general population. Cephalalgia. 2012;32:451-458.
Beiske KK, Russell MB, Stavem K. Prevalence and predictors of headache in patients referred to polysomnography. J Headache Pain. 2013;14:90.
Rezaeitalab F, Moharrari F, Saberi S, et al. The correlation of anxiety and depression with obstructive sleep apnea syndrome. J Res Med Sci. 2014;19:205-210.