Hypnic Headache in Neuro-Ophthalmology

From EyeWiki

Disease Entity

Hypnic headaches (HH) are a rare subclass of primary headaches that occur around the same time every night, awakening the patient with an estimated prevalence of 0.07-1.4% in the general population.[1]

They are also known as “clockwise headaches” or “alarm clock headaches".[1] They typically occur within 2-8 hours after sleep onset and often occur during rapid eye movement (REM) sleep.[2] They typically last for more than 15 minutes[1] They have a broad range of symptoms in terms of pain severity and characteristic.[2] They are a rare form of primary headache.


This headache syndrome was first described by Neil Raskin in 1988. It was then recognized in 2004 by the International Classification of Headache Disorders within the “other primary headache” group.[1][3] Further description, data, and understanding of the disease since then, has only come through a variety of case reports published over the years.


The etiology of HH is unknown. Although arterial hypertension and migraine have been found as comorbidities for this condition, no specific structural lesions or metabolic dysfunction has been identified as the etiology for HH.[2]

One study of 71 patients with HH found a possible association with REM sleep.[1] During REM sleep, there is arterial hypertension and low oxygenation, and this has been hypothesized to be associated with headache onset. However, there is limited response to continuous positive airway pressure (CPAP) and oxygen supplementation in patients with HH, suggesting another mechanism.[1] Another component of REM sleep is the absence of activity in the dorsal raphe and locus coeruleus nuclei.[2] These structures in association with the periaqueductal gray in the brainstem are important components of the antinociceptive system. Thus, the underlying pathophysiology may be related to the decreased activity in these regions during REM sleep, increasing the pain threshold.

Since arterial hypertension is such a common comorbidity of HH, one study emphasized the importance of 24 hours ambulatory blood pressure monitoring in the evaluation of complaints of nocturnal headache. Particularly in populations where essential hypertension is a very frequent comorbidity, such as in elderly patients.[3][4]

Another theory involves the internal human chronobiological clock since HH occur during sleep typically at the same time.[1] The suprachiasmatic nucleus (SCN) acts as the pacemaker of this biological clock through secretion of melatonin.[2] With age, there are fewer cells in the SCN and resultant decreased melatonin. This may explain why the typical demographic is adults over the age of 50. The SCN has both afferent and efferent projections to the periaqueductal gray, which as stated previously, is involved in antinociception. Thus, it could be damage or diminished function of the SCN that causes HH. Melatonin and lithium, which indirectly increases melatonin, can be therapeutic in patients with HH. However, melatonin has been found to be less efficacious that lithium, suggesting an unknown additional mechanism for HH therapy.[1]

In addition to its association with the circadian rhythm, the suprachiasmatic nucleus is located in the hypothalamus. In patients with HH, loss of hypothalamic gray matter has been found on brain imaging. The hypothalamus has some involvement in pain-mediation, so impaired function in this region may be present in patients with HH.[1] One case was reported of development of HH in a 20-year-old woman after coiling and clipping of an aneurysm after subarachnoid hemorrhage.[4] The authors hypothesized that her subarachnoid hemorrhage and aneurysm coiling and clipping caused damage to her hypothalamic-pineal axis. This hypothalamic and pituitary damage is known to occur after subarachnoid hemorrhage.[5] The authors thus hypothesized that the subarachnoid hemorrhage and resultant aneurysmal clipping and coiling may have resulted in decreased SCN function and resultant HH.[4] There is also support for hypothalamic involvement in HH from symptoms of concomitant intense thirst during episodes. Some patients are thought to have diabetes insipidus during episodes, indicating the hypothalamus is implicated.[1]

Clinical Manifestations

HH have the characteristic feature of occurring only during sleep.[6] The timing is typically at the same time every night, manifesting 2 to 8 hours after sleep onset, and lasting for a duration of 15 minutes to 4 hours.[2] The location can be either unilateral or bilateral and it often occurs almost every night.[6] The pain is typically mild to moderate and characterized as dull, but it can be severe with a throbbing or stabbing quality. Unlike cluster headaches which have overlapping features, HH do not have autonomic symptoms. Additionally, HH are less likely to have the typical nausea, photophobia and phonophobia of migraines but can rarely present with these features.[2] Demographically, HH often occur in patients over the age of 50, but have been reported in children.[7] There seems to be no difference between male and female occurrences.[1]

HH can present to ophthalmologists as retrobulbar eye pain. In patients with isolated hypnic headache, ocular exam will be normal. There should be no significant radiographic findings on magnetic resonance imaging (MRI), and electroencephalogram (EEG) should be normal.[2] It is important to investigate secondary causes of headache and eye pain, as meningioma, pontine infarcts and pituitary adenomas have been reported to present with similar nighttime headaches.[1] Giant cell arteritis and obstructive sleep apnea should also be considered in the appropriate age demographic.[2]


Diagnostic Criteria

According to the International Classification of Headache Disorders 3rd edition (ICHD-3),[6] HH are a primary headache disorder characterized by recurrent headache attacks that occur only while the patient is sleeping, causing the patient to awaken and have a headache lasting up to 4 hours without symptoms associated with another disorder. The diagnostic criteria are as follows:

A. Recurrent headache attacks fulfilling criteria B-E

B. Developing only during sleep, and causing awakening

C. Occurring on ≥ 10 days/month for > 3 months

D. Lasting from 15 minutes up to four hours after waking

E. No cranial autonomic symptoms or restlessness

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


HH is a diagnosis of exclusion, per ICHD criteria.[6] Evaluation includes polysomnography, cerebral MRI, complete blood count, erythrocyte sedimentation rate, C-reactive protein, 24-hour blood pressure monitoring, urine metanephrines, dental exam, and toxicology screen.[8]

Differential Diagnosis

The following differentials should be considered in a patient presenting with headaches during sleep:[1][6]

  • Other primary headache disorders
    • Cluster headache
    • Migraines
  • Secondary causes of headache
    • Sleep apnea
    • Nocturnal hypertension
    • Medication overuse
    • Intracranial tumors: meningioma, pituitary adenoma
    • Infarction

Brain imaging and investigation of systemic disorders should be done to evaluate for the above diagnoses.



Lithium has been found to have the best efficacy for prophylaxis.[2] Calcium, melatonin, indomethacin, and caffeine have also been found to have some efficacy.[2] Typical medications for cluster headaches and migraines have not been found to be useful, such as subcutaneous sumatriptan and oxygen inhalation in the acute attacks.[1] Antidepressants, beta blockers, verapamil, and anticonvulsants have limited use and have not been shown to be effective.[1]


  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 Lanteri-Minet M, Donnet A. Hypnic headache. Curr Pain Headache Rep. 2010 Aug;14(4):309-15. doi: 10.1007/s11916-010-0124-8.
  2. 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 Evers S, Goadsby PJ. Hypnic headache: clinical features, pathophysiology, and treatment. Neurology. 2003;60:905–909.
  3. 3.0 3.1 Gil-Gouveia R, Goadsby PJ. Secondary "hypnic headache". J Neurol. 2007 May;254(5):646-54. doi: 10.1007/s00415-006-0424-4.
  4. 4.0 4.1 4.2 Aldred, M., Raviskanthan, S., Mortensen, P. W., & Lee, A. G. (2022). Hypnic Headaches in a Patient Post Coiling and Clipping of Intracranial Aneurysm. Journal of Neuro-Ophthalmology, 42(1), e415–e416. https://doi.org/10.1097/WNO.0000000000001284
  5. Schneider HJ, Kreitschmann-Andermahr I, Ghigo E, Stalla GK, Agha A. Hypothalamopituitary dysfunction following traumatic brain injury and aneurysmal subarachnoid hemorrhage: a systematic review. JAMA. 2007;298:1429–1438.
  6. 6.0 6.1 6.2 6.3 6.4 Headache Classification Committee of the International Headache Society (IHS). The international classification of headache disorders, 3rd edition. Cephalalgia. 2018;38:54–55.
  7. Silva-Néto RP, Almeida KJ. Hypnic headache in childhood: a literature review. J Neurol Sci. 2015;356:45–48.
  8. Holle D, Naegel S, Obermann M. Hypnic headache. Cephalalgia. 2013;33(16):1349-1357. doi:10.1177/0333102413495967
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