Keywords::
Sleep apnea headache is an infrequent form of secondary headache in spite of the prevalence of its causal condition, the sleep apnea. Its real prevalence is uncertain for several reasons: differences of the studies (population-based or clinical studies), differences of diagnostic criteria used in the past years and the frequent alternative, even incorrect, use of morning headache instead of sleep apnea headache (being the second a subgroup of the first, that in turn is a unspecific condition).
Headache present at the awakening in the morning, after the nocturnal sleep, has been found associated with a great number of clinical conditions including sleep disorders, primary headache transformation/chronification, psychological distress, intracranial hypertension, and so on.
The recent classification ICHD III, of which the beta version is already available, has introduced some changes with respect to the second version (ICHD II–2004) in an effort to consolidate useful and precise diagnostic criteria, indispensable to select patients affected by sleep apnea headache, a fundamental step to investigate its epidemiology and pathophysiology.
In both ICHD-II Citation[1] and ICHD-III Citation[2] classification, the secondary headache group included the group ‘10 headache attributed to homeostasis disorders’ that in turn included the subgroup ‘10.1 headache attributed to hypoxia and/or hypercapnia’ of which the subsubgroup 10.1.3 of the ICHD-II and the 10.1.4 of ICHD-III is labelled as ‘sleep apnea headache.’
For ICHD II, sleep apnea headache is a recurrent headache with at least one of the following characteristics (>15 days per month; bilateral, pressing quality and not accompanied by nausea, photophobia or phonophobia; each headache resolves within 30 min), which occurs in subjects with polysomnographic demonstration of sleep apnea (Respiratory Disturbance Index ≥5) in which headache is present upon awakening and which ceases within 72 h and does not recur after effective treatment of sleep apnea. In the comment to ICHD-II 10.1.3 diagnostic criteria, it is put in evidence that “although morning headache is significantly more common in patients with sleep apnoea than in the general population, headache present upon 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 apnoea.”
In ICHD-III (beta version), 10.1.4 sleep apnea headache is described as a morning headache, usually (though nonmandatorily) bilateral and with a duration of <4 h, caused by sleep apnea that resolves with successful treatment of the sleep apnea. Also according to ICHD-III 10.1.4 diagnostic criteria, sleep apnea headache has to be present on awakening after sleep; in a patient with demonstrated sleep apnea (Apnea Hypopnea Index ≥5) and fulfilling Criterion C, the fundamental one to define the cause–effect link between a certain headache and the presence of sleep apnea. The Criterion C (evidence of causation) requires at least two of the following:
• Headache has developed in temporal relation to the onset of sleep apnea;
• Either or both of the following:
– Headache has worsened in parallel with worsening of sleep apnea;
– Headache has significantly improved or remitted in parallel with improvement in or resolution of sleep apnea
• Headache has at least one of the following three characteristics:
– Recurs on >15 days per month;
– All of the following: bilateral location; pressing quality; and not accompanied by nausea, photophobia or phonophobia;
– Resolves within 4 h.
Comparing the two versions, the major modification is the duration of sleep headache attacks that increases from 30 min to 4 h.
The removal of Criterion D of ICHD-II is only apparent: it has been transformed in a part of the C criterion of ICHD-III. In fact, even if someone may suppose that now we may diagnose sleep apnea headache even if it remains unchanged notwithstanding a successful treatment of the sleep apneas, the cause–effect relationship between sleep apneas and headache has to be mandatorily demonstrated: we have to demonstrate that the headache onset is the consequence of the apneas onset, or we have to show that the headache worsen when the frequency/severity of apneas increases and/or it improves when the frequency/severity of apneas decreases.
The importance of the demonstration of the causation link between sleep apneas and headache is unchanged, but now it may also be demonstrated in the opposite way: that is Criterion C – headache has worsened in parallel with worsening of sleep apnea.
Probably, the D criterion of the ICHD-II was clearer and reduced the possibility of ‘subjective’ interpretations: headache that ceases within 72 h and that does not recur, after effective treatment of sleep apnea is unambiguous, whereas “headache has developed in temporal relation to the onset of sleep apnoea and/or either or both of (a) headache has worsened in parallel with worsening of sleep apnoea, (b) headache has significantly improved or remitted in parallel with improvement in or resolution of sleep apnoea,” does not specify the required amount of the improving/worsening neither the temporal interval between apnea variation and consequent headache change. We hope that this reduced precision in criteria will not induce additional confusion in the diagnostic phase.
Without the demonstration of the causal link between sleep apneas and sleep apnea headache, independently by the use of ICHD-II or ICHD-III criteria, patients included in the diagnosis of ‘sleep apnoea headache’ may be very different: headache may be migraine-, tension type- and probably also cluster-like. The Criterion A of ICHD-II version includes the description of symptoms of the sleep apnea headache attack (bilateral, pressing quality and not accompanied by nausea, photophobia or phonophobia), but this criterion states only that at least one of the three elements listed is needed for the diagnosis (>15 days per month and/or bilateral, pressing quality and not accompanied by nausea, photophobia or phonophobia and/or each headache resolves within 30 min). Consequently, using ICHD-II criteria, all patients with >15 days of morning headache and sleep apnea may fit the A1 criterion, independently by the characteristics of headache attack (Criterion A2). Also frequent attacks of short-lasting headache in the morning, independently by frequency and features, are satisfactory for this criterion. ICHD-III version describes sleep apnea headache as a morning headache, usually bilateral and with a duration of less than 4 h, but diagnostic criteria require that morning headache in a patient with demonstration of sleep apneas has to present (subcriterion C3) 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 and (iii) not accompanied by nausea, photophobia or phonophobia; c) resolves within 4 h. If Criteria C1 and C2 are observed, the diagnostic Criterion C3 is not essential. Additionally, even if only Criterion C1 or C2 is respected, C3 may be satisfied by frequency >15 days per month or by duration (maximum 4 h), independently by clinical features of the attack. Consequently, frequency of attacks, duration of attacks, clinical manifestations of attacks are alternatively required, not necessarily copresent, and, in consequence, substantially every kind of headache present on awakening after sleep in a sleep apnea patient, may be hypothesized as sleep apnea headache, but it can be diagnosed only if the causative relationship with apneas is demonstrated.
As paradoxical example, without a rigorous demonstration of the causation, we may wrongly diagnose as ‘sleep apnoea headache’ also a patient with sleep apnea, which complains a typical cluster-like headache that lasts 2 h (Criterion C3c), recurring everyday (Criterion C3a), in the morning on awakening (Criterion A) that appeared after the diagnosis of sleep apnea (Criterion C1). Moreover, it has been observed that sleep apneas are very frequent in both cluster headache Citation[3] and in patent foramen ovale Citation[4] that in turn is very frequent in cluster headache Citation[5,6]: in these patients, the copresence of sleep apneas and patent foramen ovale may have a cumulative effect on oxygen desaturation during night that is known to worsen cluster headache (that in fact is ameliorated by oxygen administration). Consequently, it is probable that in the hypothetic described case, some improvement of the headache condition may also be observed as a consequence of a valid treatment of the sleep apnea, with the risk to fit also the ICHD-III subcriterion for causation. If the application of new diagnostic criteria will enlarge the possibility of diagnostic confusion between primary headaches with sleep apneas and sleep apnea headache, then pathophysiological investigations will also be negatively influenced.
Only with the correct application of rigorous diagnostic criteria, we might try to identify the real epidemiology and pathophysiology of sleep apnea headache, which has been controversial until now, controversial probably as a consequence of dissimilar cohorts of patients studied in previous studies.
The evidence of causation is the fundamental element in all secondary headaches: primary headaches are more frequent than secondary headache, and symptoms are often similar. Consequently, a possible comorbidity has to be always excluded.
On the other hand, sleep apnea headache has to be excluded when we want to evaluate the effect of sleep apneas on the evolution of a pre-existing primary headache Citation[3,7], in studies of reciprocal interference of sleep apneas and primary headache Citation[8] or in a better definition of possible causes of morning headaches Citation[9].
And last but not least, the diagnostic element that is never taken in account by ICHD diagnostic criteria is the previous presence of a primary headache: the cephalalgic history of the patient may give important information about his/her brain predisposition to headache: multiple data have underlined that, for example, migraineurs brain is metabolically different, with a clear tendency to develop headache in the consequence of endogenous and exogenous situations, possibly including sleep apneas. It may be possible that the key to individuate sleep apnea headache pathophysiology (sleep apnea headache present only in a minority of sleep apnea patients, apparently without relationship with apnea severity) consists in a predisposition too (a ‘predisposed brain’).
Financial & competing interests disclosure
The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
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