Primary care doctor: Because of the patient's age and the
absence of a headache history, I first considered such secondary
causes as tumor and temporal arteritis. However,
MRI of the brain and erythrocyte sedimentation rate were
normal. I now suspect a sleep-related headache because
the attacks occur only at night and awaken the patient
from a sound sleep. How can I determine which type of
sleep-related headache is involved?
Headache specialist:The first step is to assess the severity,
pain location, and presence of autonomic features.
"Nocturnal attack" headaches include hypnic headache,
cluster headache, chronic and episodic paroxysmal hemicrania,
and SUNCT (short-lasting, unilateral, neuralgiform
hemicrania with conjunctival injection and tearing)
Patients with nocturnal attack headaches generally
describe the pain as throbbing or stabbing. Cluster headaches
and chronic and episodic paroxysmal hemicrania
produce very severe pain; hypnic headaches and SUNCT
syndrome headaches produce moderately severe pain.
syndrome headaches produce moderately severe pain.
The pain of cluster headaches, chronic and episodic
paroxysmal hemicrania, and SUNCT syndrome is typically
unilateral at the orbit or temple. Patients with hypnic
headaches commonly experience diffuse, dull or throbbing,
global pain; unilateral pain is rare.1-4
Sleep-related headaches- with the exception of hypnic
headaches-are associated with autonomic symptoms.
Doctor: Because my patient has no autonomic symptoms, hypnic headache is the most likely diagnosis. How common
is this type of headache?
Headache specialist: Raskin5 first described hypnic headache
as a rare condition that primarily affects elderly
women (the female-to-male ratio is 2:1).
Recently, researchers have proposed that hypnic
headache may be a spectrum disorder, because the headaches
range from mild, bilateral, 5-minute attacks to severe,
unilateral, throbbing attacks that can last up to 6
hours (Table).2Headache specialist: Researchers believe that fluctuations
in the levels of serotonin and other brain neurotransmitters
that occur during sleep can affect headaches.
In one study, researchers described the case of a
79-year-old woman with an 11-year history of nocturnal
headaches that suggested hypnic headache.6 A polysomnographic
study showed arousal at stage 3 slow wave sleep
because of a headache episode. Although this finding may
have been nonspecific, it suggests the possible relationship
between stage 3 slow wave sleep and hypnic headache.7
In another report, the author conducted overnight
polysomnographic studies of 3 patients with long-standing
hypnic headache.8 The results ranged from normal
to marked sleep insufficiency. A hypnic headache was revealed
in 1 patient who awoke from rapid eye movement
sleep at a time of severe oxygen desaturation. The author
suggested that formal sleep evaluation be considered for
patients with hypnic headache because there may be
pathophysiologic and therapeutic implications.
Doctor: What is the pathophysiology of hypnic headache?
Headache specialist:We don'tyet have all the answers.
Raskin wrote that the pathophysiology of the hypnic headache resembles that of the chronic form of cluster
headache (migrainous neuralgia).5 The mechanism of
these 2 syndromes may be similar because both appear to
involve the pacemaking mechanism in the hypothalamus
that controls circadian rhythm. This theory is supported
by the remarkable response of both types of headache to
lithium therapy. Since the hypothalamic pacemaker is
serotonergically innervated and lithium has been shown
to enhance serotonergic neurotransmission, it seems reasonable
to suppose that perturbed serotonergic neurotransmission
underlies both disorders.
Substantial laboratory evidence indicates that lithium
stabilizes and enhances serotonergic neurotransmission in
the hippocampus, the site at which serotonin receptors
are down-regulated during lithium treatment. This may
also slow and alter circadian rhythms.
Doctor: What dosage of lithium is recommended for patients
with hypnic headache? Are effective alternatives
Headache specialist: Hypnic headaches may be treated
with lithium at a starting dosage of 300 mg every night
that is slowly increased to 900 mg/d. However, the side
effects of lithium, such as tremor and impaired memory,
make it intolerable for some elderly patients.
Indomethacin may be an option for some patients
who are not helped by lithium. In one study, indomethacin
was effective in 7 patients with hypnic headache.9 Four
patients had a substantial reduction in the frequency and
severity of headaches, and 3 had complete suppression of
headaches. However, 2 of those 3 experienced severe daytime headaches, which resolved when indomethacin was
discontinued. Flunarizine, caffeine, or verapamil may also
be tried as an alternative to lithium.7,9
1. Gould JD, Silberstein SD. Unilateral hypnic headache: a case study. Neurology.
2. Dodick DW, Mosek AC, Campbell JK. The hypnic (“alarm clock”) headache
syndrome. Cephalalgia. 1998;18:152-156.
3. Ivanez V, Soler R, Barreiro P. Hypnic headache syndrome: a case with good
response to indomethacin. Cephalalgia. 1998;18:225-226.
4. Morales-Asin F, Mauri JA, Iniguez C, et al. The hypnic headache syndrome:
report of three new cases. Cephalalgia. 1998;18:157-158.
5. Raskin NH. The hypnic headache syndrome. Headache. 1988;38:534-536.
6. Arjona JA, Jimenez-Jimenez FJ, Vela-Bueno A, Tallon-Barranco A. Hypnic
headache associated with stage 3 slow wave sleep. Headache. 2000;40:753-754.
7. Evers S, Goadsby PJ. Hypnic headache: clinical features, pathophysiology,
and treatment. Neurology. 2003;60:905-909.
8. Dodick DW. Polysomnography in hypnic headache syndrome. Headache.
9. Dodick DW, Jones JM, Capobianco DJ. Hypnic headache: another indomethacin-
responsive headache syndrome? Headache. 2000;40:830-835.
10. Goadsby PJ, Lipton RB. A review of paroxysmal hemicranias, SUNCT syndrome
and other short-lasting headaches with autonomic feature, including new
cases. Brain. 1997;120:193-209.