Nighttime Headache

A cadre of primary and secondary headache disorders have a predilection for stalking the night, striking in the wee hours, adding in pain and misery what they subtract in restful slumber (Case Study Presentation). Although far less common than that ubiquitous grand dame of headache disorders, migraine, these headache types need to be recognized because some are easily treatable (and treatment options vary wildly depending on the type) and others, if not detected, may be ominous.

Hypnic Headache

If this small but important group of nocturnal headache maladies had its own grand dame, it would be hypnic headache, an exclusively nighttime headache with alarm-clock-like precision of arrival (Box 1).1,2 Onset of hypnic headache is commonly after age 50 (reported average age of onset is 62, with a range of 30-84), and it is more common in woman. Estimates in the US and Germany are that 0.1% of primary headaches are hypnic, and time to diagnosis is 1 to 35 years (mean 5 years) after onset, suggesting hypnic headache is not well-recognized in the medical community. The pain may be unilateral or bilateral, often lasting a few hours, with an intensity described as mild in 4%, moderate in 60%, and severe in 37% of cases. Autonomic features are rare. Polysomnography reveals that hypnic headache occurs frequently during rapid eye movement (REM) sleep, often the first REM cycle of the night, corresponding to the observation that the pain of hypnic headache usually wakes people from a dream. Multiple attacks occurring during multiple REM phases have been reported. Unfortunately, there has been little research on hypnic headache, and the exact physiology remains to be elucidated.

Cluster Headache

More common in men than women, cluster headache (CH) occurs in about 0.1% of the population and has circadian and seasonal rhythmicity (Box 2).2,3 Although cluster attacks may occur during the day, the majority awaken the individual about 1 to 3 hours after they fall asleep with severe unilateral orbital pain and autonomic features such as eye tearing and redness, lid droop, and nasal congestion—all on the side of the pain. People with CH have been shown to be poor sleepers even between cluster cycles and to have lower circulating melatonin levels and a desynchrony between melatonin and cortisol compared with those without CH. At least 3 separate systems are involved in CH, including the trigeminovascular system, the autonomic nervous system (via the sphenopalentine ganglion), and the hypothalamus. The suprachiasmatic nucleus (SCN), which functions as a circadian clock, lies within the hypothalamus. Recently, a significant association was found between CH and a single nucleotide polymorphism (SNP: rs12649507) in the circadian locomotor output cycles kaput (clock) gene, which is expressed in the SCN.4

Other Primary Nocturnal Headaches

Migraine. There is also a circadian pattern for many who have migraine.5 When a nocturnal migraine strikes, it is often at the end of sleep—unlike hypnic headache or CH, which both tend to occur earlier. Approximately half of migraines begin between 4:00 am and 9:00 am, waking the individual with a headache that is often of maximal intensity and centrally sensitized and, thus, refractory to oral triptans. Injectable triptans are first-line treatment for these migraine attacks.

Bruxism. With or without temporomandibular joint (TMJ) disorder, bruxism (teeth grinding) may occur during sleep and cause nighttime headaches. Pain is usually dull moderate intensity bilateral and centered about the temples, midface, and forehead. Treatment includes nonsteroidal anti-inflammatories (NSAIDs), muscle relaxants, and the use of nighttime mouth guards. If masseter hypertrophy is detected, onobotulinumtoxinA injections are often useful.

Cervicogenic Headache. Frequently worse at night, cervicogenic headache wakes the individual with neck pain radiating to the occiput and anteriorly to the forehead and is caused by mechanical neck position during sleep. A comfortable, supportive pillow is helpful.

Obstructive Sleep Apnea. In addition to snoring and daytime sleepiness, obstructive sleep apnea (OSA) may cause nocturnal or awakening headache in approximately 50% of affected individuals.7 These mild-to-moderate severity headaches typically resolve within 72 hours of starting continuous positive airway pressure (CPAP).

Other Primary Headaches. Tension-type headache, hemicrania continua, and the trigeminal autonomic cephalalgias SUNCT and SUNA may also occur in the night. Idiopathic intracranial hypotension (pseudotumor cerebri) headache may be worse when lying down and can disrupt sleep. Less intuitively obvious, spontaneous intracranial hypotension may wake the affected individual in the wee hours of the morning (Linda Gray Leithe, MD, personal communication).

Secondary Headaches. Sinusitus, brain tumor (primary or metastatic), nocturnal hypertension, hypoglycemia, and medication overuse headache are secondary headaches with a predilection for nocturnal misbehavior.

Conclusion

There are many headaches that may occur at night, some of which can be intensely painful and intensely regular, preventing sleep and affecting quality of life significantly. Proper diagnostic workup is essential to determine which headache is causing bumps in the night.

Sleep well, readers!

1. Silva-Néto RP, Santos PEMS, Peres MFP. Hypnic headache: a review of 348 cases published from 1988 to 2018. J Neurol Sci. 2019;401:103-109.

2. Olesen J. Headache Classification Committee of the International Headache Society (IHS) the international classification of headache disorders, asbtracts. Cephalalgia. 2018;38(1):1–211

3. Nesbitt AD, Goadsby P J. Cluster headache. BMJ. 2012;344:e2407.

4. Gibson KF, Santos AD, Lund N, Jensen R, Stylianou IM. Genetics of cluster headache. Cephalalgia. 2019 Sep;39(10):1298-1312.

5. Burish MJ, Chen Z, Yoo S-H. Emerging relevance of circadian rhythms in headaches and neuropathic pain. Acta Physiol (Oxf). 2019;225(1):e13161.

6. Robbins MS; StarlingAJ, Pringsheim TM, Becker WJ, Schwedt TJ. Treatment of cluster headache: The American Headache Society evidence-based guidelines. Headache. 2016;56(7):1093-1106.

7. N. Foldvary, DO; et al. Do patients with obstructive sleep apnea wake up with headaches? Arch Intern Med. 1999;159(15):1765-1768.