Cluster Headache

Epidemiology

Cluster headache, which is much less common than tension-type headache or migraine, affects
0.4 to 2.4 persons per 1000 in the general population. Unlike patients with migraine headaches,
those with cluster headaches usually seek medical consultation because of the intense pain that
accompanies their attacks. As a result, physicians encounter cluster headache more frequently
than would be predicted from its actual prevalence. The condition is more common in men than
in women (male-to-female ratio of 6:1) and usually begins in the third through the sixth decades
of life. Although cluster headaches may cease during pregnancy, attacks seldom correlate with
menses.

Pathobiology

The cause of cluster headaches is not defined. Like other vascular headaches, they are presumed
to develop from events that ultimately activate the trigeminovascular system. In the complete
form of the disease, patients with cluster headache manifest pain referred to the first and second
trigeminal divisions, sympathetic dysfunction (i.e., Horner's syndrome), sympathetic activation
(i.e., sweating of the forehead and face), and parasympathetic activation (i.e., lacrimation and
nasal congestion). This constellation of symptoms and signs is best explained by the presence of
a single lesion at the point at which fibers from the ophthalmic and maxillary trigeminal division
converge with projections from the superior cervical and sphenopalatine ganglia. This plexus is
located within the cavernous sinus, and narrowing of the cavernous carotid artery has been
observed in selected cases of cluster headache. PET-based functional imaging studies of blood
flow during acute cluster attacks show areas of increased flow in the inferior portion of the
hypothalamus on the same side as the headache. This finding is consistent with the clinical
cyclicity exhibited by cluster headaches reported by many patients.

There is an increased concordance of cluster headache in monozygotic twins. Moreover, studies

of relatives of patients with cluster headache have found a frequency 13 times higher than
expected by chance.

Clinical Manifestations

Cluster headaches consist of recurrent episodes of unilateral, orbital, supraorbital, or temporal

head pain usually accompanied by ipsilateral autonomic signs, including conjunctival injection,
lacrimation, rhinorrhea, nasal congestion, ptosis, miosis, eyelid edema, and facial sweating. The
attacks last 15 minutes to 3 hours and occur as infrequently as every other day to as frequently as
eight attacks per day. The syndrome derives its name from the characteristic clusters or periods
of frequent headaches that last weeks to months and are separated by periods of months or years
of headache-free remission. Chronic symptoms without remission may develop in about 10% of
patients. During a cluster period, the headache attacks often assume a temporal cyclicity, with
occurrence at almost the same time every day. Exposure to small amounts of nitrates or alcohol
may trigger an acute attack during a cluster period.

Treatment
During cluster headaches, oxygen inhalation (100%) delivered at a rate of 8 L/min for 15
minutes through a loose-fitting facemask is a safe and effective treatment of acute attacks,
particularly in patients younger than 50 years who have episodic cluster headaches. Patients
who respond to oxygen usually do so within 10 minutes. Inhalation of oxygen does not cause
nausea and is not contraindicated in patients with coronary artery disease or peripheral vascular
disease. Ergotamine tartrate, the classic treatment of cluster headache, is effective and well
tolerated by many patients. Because of more rapid absorption, sublingual administration (1 mg)
is generally preferred to oral administration (1 mg). Intranasal dihydroergotamine (1 mg)
reduces the severity of cluster headaches, but not their duration. Subcutaneous administration
of sumatriptan (6 mg), which is usually successful in alleviating acute cluster headaches,
reduces pain and conjunctival injection within 15 minutes in most patients. Vasoconstrictive
medications such as ergotamines and sumatriptan should be used with caution for cluster
headache in patients who are at increased risk for coronary artery disease.

For many years ergotamine tartrate was the only prophylactic agent used for cluster headache.
It is effective and well tolerated in doses of 2 to 4 mg/day given orally or by suppository. The
ergot derivative methysergide (4 to 8 mg/day) is effective in about 70% of episodic cases.
Retroperitoneal, pleural, or pericardial fibrosis is a severe potential side effect of long-term use.
Because patients with cluster headache generally require treatment for less than 2 to 3 months,
methysergide, if available, can be used with more safety than in migraine. Lithium carbonate,
which was effective in chronic cluster headache in more than 20 open-label clinical trials, may
also be beneficial in the episodic form of the disease. Because of the narrow range between
toxic and therapeutic doses, it is important to monitor the serum lithium level 12 hours after the
last dose. Average daily doses of lithium carbonate (600 to 900 mg) should be titrated
according to the serum lithium level; the usual therapeutic range is 0.3 to 0.8 mmol/L, but low
lithium levels may still be therapeutic. NSAIDs and thiazide diuretics may increase serum
lithium levels. Verapamil (240 to 480 mg/day) is often effective as a prophylactic agent against
cluster headache; it has relatively few side effects when compared with other prophylactic
agents, and a double-blind trial found it to be as effective as lithium. Prophylactic medication
dosages are usually tapered and then discontinued within 3 to 6 weeks after recurrent cluster
headaches cease.

Corticosteroids are often used to treat the episodic and the chronic forms of cluster headache,
even though evidence for their effectiveness is largely limited to open trials. Prednisone is
frequently used in dosages of 60 to 80 mg/day for 1 week, followed by a taper in dosage over a
period of 2 to 4 weeks.