Lori K Sargeant, MD,
Consulting Staff, Summa Emergency Associates,
Inc
Nothing to disclose.
Coauthor(s)
Michelle Blanda, MD,,
Chair, Department of Emergency Medicine,
Summa Health System Akron City/St. Thomas Hospital; Professor
of Emergency Medicine, Northeastern Ohio Universities College
of Medicine
Nothing to disclose.
Specialty Editor(s)
Edward A Michelson, MD,
Associate Professor, Program Director,
Department of Emergency Medicine, University Hospital Health
Systems in Cleveland
Nothing to disclose.
Francisco Talavera, PharmD, PhD,
Senior Pharmacy Editor,
eMedicine
eMedicine Salary Employment
J Stephen Huff, MD,
Associate Professor, Emergency Medicine and
Neurology, Department of Emergency Medicine, University of
Virginia Health Sciences Center
Nothing to disclose.
John D Halamka, MD, MS,
Associate Professor of Medicine, Harvard
Medical School, Beth Israel Deaconess Medical Center; Chief
Information Officer, CareGroup Healthcare System and Harvard
Medical School; Attending Physician, Division of Emergency
Medicine, Beth Israel Deaconess Medical
Center
Nothing to disclose.
Chief Editor
Steven C Dronen, MD, FAAEM,
Chair, Department of Emergency Medicine,
LeConte Medical Center
Nothing to disclose.
Background
Cluster headache, also known as histamine headache, is a form of neurovascular headache. Attacks usually are severe and unilateral and typically are located at the temple and periorbital region. The pain is typically associated with ipsilateral lacrimation, nasal congestion, conjunctival injection, miosis, ptosis, and lid edema. Each headache is brief in duration, typically lasting a few moments to 2 hours. Cluster refers to a grouping of headaches, usually over a period of several weeks. To fulfill criteria for diagnosis, patients must have had at least 5 attacks occurring from 1 every other day to 8 per day and no other cause for the headache.
The 2 existing forms of cluster headache are (1) episodic clusters with at least 2 cluster phases lasting 7 days to 1 year separated by a cluster-free interval of 1 month or longer, and (2) chronic form, in which the clusters occur more than once a year without remission or the cluster-free interval is less than 1 month.
The pathophysiology of cluster headaches is not well understood. Some proposed mechanisms are described here.
Hemodynamic: Vascular dilatation may play a role, but blood flow studies are inconsistent. Extracranial blood flow (hyperthermia and increased temporal artery blood flow) increases but following the onset of pain. Vascular change is considered secondary to primary neuronal discharge.
Trigeminal nerve: The trigeminal nerve may be responsible for neuronal discharge causing cluster headaches. Substance P neurons carry sensory and motor impulses in the maxillary and ophthalmic divisions of the nerve. These connect with the sphenopalatine ganglion and interior carotid perivascular sympathetic plexus. Somatostatin inhibits substance P and reduces the duration and intensity of cluster headaches.
Circadian rhythm: Cluster headaches often recur at the same time every day, suggesting that the hypothalamus, which controls circadian rhythms, may be the site of activation.
Serotonin: This is not as striking as in migraines, but some changes are seen.
Histamine: Although evidence supporting a causative role is inconsistent, cluster headaches may be precipitated with small amounts of histamine. Antihistamines do not abort cluster headaches.
Mast cells: Increased numbers of mast cells have been found in the skin of painful areas of some patients, but this finding is inconsistent.
Incidence is estimated to be 2-9% of migraine sufferers, making it relatively uncommon compared with classic migraines. Prevalence in males is 0.4-1%.
International
Incidence in the United Kingdom is equivalent to that of multiple sclerosis.
Mortality/Morbidity
No reported mortality is directly associated with cluster headaches, although suicides have been reported in cases where attacks are frequent and severe. The intensity of the attacks often leads those who experience cluster headaches to miss time from activities such as work or school.
Race
Cluster headaches may be underdiagnosed in black women, but ethnic differences have not been studied.
Sex
This condition is more common in males than in females. The male-to-female ratio was 6:1 in the 1960s but now is 2:1.
Age
Cluster headaches usually begin in middle adult life. The mean age of onset is 30 years for men and later for women.
No aura exists as in migraines. Periodicity is the most striking characteristic. Typically, a patient experiences 1-2 cluster periods per year, each lasting 2-3 months.
Pain - Described as lancinating and severe
Sudden onset - Peaks in 10-15 minutes
Unilateral facial - Remains on the same side during the cluster period
Duration - 10 minutes to 3 hours per episode
Character - Boring and lancinating, as if eye is being pushed out
Distribution - First and second divisions of the trigeminal nerve (Approximately 18-20% of patients complain of pain in the extratrigeminal areas [eg, back of the neck, along carotid artery].)
Frequency - May occur several times a day for 1-4 months (often nocturnal)
Periodicity - Circadian regularity in 47%
Remission - Long symptom-free intervals occur in some patients. The average remission is 2 years but ranges from 2 months to 20 years.
Lacrimation (84-91%) or conjunctival injection
Nasal stuffiness (48-75%) or rhinorrhea
Ipsilateral eyelid edema
Ipsilateral miosis or ptosis
Ipsilateral forehead and facial perspiration (26%)
Physical examination findings should be normal except for the lacrimation and conjunctival injection that may occur. Ptosis can also be seen. Accompanying findings are consistent with ipsilateral autonomic features characterized by cranial parasympathetic activation and sympathetic hypofunction. The presence of other abnormalities suggests another etiology for the headache.
Subcutaneous injection of histamine provokes attacks in 69% of patients.
Attacks are triggered in some patients by stress, allergens, seasonal changes, or nitroglycerin.
Alcohol induces attacks during a cluster but not during remission. Of patients with cluster headache, 80% are heavy smokers and 50% have history of heavy ethanol use.
Oxygen (8 L/min for 10 min or 100% by mask) may abort the headache if used early.
Mechanism of action is unknown.
Sumatriptan[1, 3, 2]
Sumatriptan is the most studied of the triptans in cluster headache. Subcutaneous injections can be effective, in large part, due to the rapidity of onset. Studies have indicated that intranasal administration is more effective than placebo but not as effective as injections. No evidence suggests that they are effective orally. Typical dose is 6 mg SQ with the ability to repeat in 24 hours. Nasal spray (20 mg) may also be used.
Early studies are encouraging.
Dihydroergotamine
Can be abortive agent
IV/IM; self-injections
Intranasal 0.5 mg bilaterally[2]
Analgesics/narcotics: Oral route levels are inadequate until attack is complete but often are helpful for residual soreness. Abuse potential does exist.
Civamide and capsaicin: When applied to the nasal mucosa of patients with cluster headaches, a clinically significant decrease occurred in the number and severity of cluster headaches. Nasal burning was the most common adverse effect.
Lidocaine: 1 mL of a 10% solution placed on a swab in each nostril for 5 minutes is possibly helpful.
Diagnosis and treatment guidelines are available from the American College of Emergency Physicians and National Headache Foundation.[4, 3]
The goal of pharmacotherapy is to prevent the attack or alter it once it is underway. An accurate diagnosis is required when therapy is being considered.
5-HT1 receptor agonists such as sumatriptan or dihydroergotamine (DHE) with metoclopramide are often the first line of treatment. Parenteral opiates may be used if relief is inadequate. Antihistamines, such as chlorpromazine, do not appear to be helpful in relieving cluster headache symptoms. Tricyclic antidepressants are more helpful as prophylaxis of other headache syndromes. Beta-blockers may worsen bradycardia occurring during the cluster attack.
These agents are effective for cluster headaches that do not respond to lithium. They are intended for intermittent use during acute flare-ups. High doses of corticosteroids can ease pain within 8-12 h, with maximum effectiveness in 2-3 d.
Clinical Context:
May suppress factors producing headaches. Should be used for short-lasting cluster attacks and not for prolonged therapy. More than 50% of patients show improvement.
Clinical Context:
Antidopaminergic drug that blocks postsynaptic mesolimbic dopamine receptors, has anticholinergic effect, and can depress reticular activating system, possibly responsible for relieving nausea and vomiting.
Lithium has been suggested as a therapy option because of the cyclical nature of cluster headaches, which is similar to the cyclical episodes in bipolar disorders.
Clinical Context:
Used to treat episodic and chronic cluster headache attacks. Mechanism of action unknown, although stabilization of biologic membranes may occur. Patients with chronic syndrome more responsive. Tendency for effect to wane after dramatic relief in first week.
These agents may alleviate headache pain by inhibiting prostaglandin synthesis, reducing serotonin release, and blocking platelet aggregation. Although the effects of NSAIDs in the treatment of headache pain tend to be patient specific, ibuprofen is usually the DOC for the initial therapy. Other options include naproxen, ketoprofen, and ketorolac.
Clinical Context:
Inhibits prostaglandin synthesis by decreasing activity of enzyme cyclooxygenase, which results in decreased formation of prostaglandin precursors.
Clinical Context:
NSAID; inhibits cyclooxygenase (COX), an early component of the arachidonic acid cascade, resulting in reduced synthesis of prostaglandins, thromboxanes, and prostacyclin. Elicits anti-inflammatory, analgesic, and antipyretic effects. Indicated for short-term (up to 5 d) management of moderate to moderately severe pain. Bioavailability of 31.5-mg intranasal dose (2 sprays) is approximately 60% of 30-mg IM dose. Intranasal spray delivers 15.75 mg per 100-µL spray; each 1.7-g bottle contains 8 sprays.
These are direct vasoconstrictors of smooth muscle in cranial blood vessels. Their activity depends on CNS vascular tone at the time of administration.
Clinical Context:
Has alpha-adrenergic antagonist and serotonin antagonist effects. Causes constriction of peripheral and cranial blood vessels. Oral administration of ergotamine not as effective as inhaled or sublingual routes in treatment of acute cluster attacks.
Clinical Context:
Used to treat acute migraine. Selective 5-HT1B/1D receptor agonist. Results in cranial vessel constriction, inhibition of neuropeptide release, and reduced pain transmission in trigeminal pathways.
Clinical Context:
Selective 5-HT1B/1D receptor agonist. Results in cranial vessel constriction, inhibition of neuropeptide release, and reduced pain transmission in trigeminal pathways. Has unique characteristics and benefits in the acute treatment of migraine. Studies demonstrate prolonged presence of frovatriptan in bloodstream, and few migraine patients experienced recurrence of headache within 24 h of taking frovatriptan.
Clinical Context:
As selective agonists of serotonin 5-HT1 receptors in cranial arteries, cause vasoconstriction and reduce inflammation associated with antidromic neuronal transmission in cluster headache. Can reduce severity of headache within 15 min of SC injection.
Clinical Context:
As selective agonists of serotonin 5-HT1 receptors in cranial arteries, cause vasoconstriction and reduce inflammation associated with antidromic neuronal transmission in cluster headache. Can reduce severity of headache within 15 min of SC injection.
Clinical Context:
Selective agonist for serotonin 5-HT1 receptors in cranial arteries and suppresses the inflammation associated with migraine headaches.
Popular in the 1940s and 1950s, histamine desensitization was introduced by Dr Horton at the Mayo Clinic. He treated patients with subcutaneous and intravenous injections. This treatment was based on the contention that metabolic derangement of histamine played an important role in producing cluster headaches.
This treatment is used very rarely at the present time.
Results were inconsistent. Minimal hard data exist on recurrence rates and follow-up duration.
The episodic nature of clusters was not recognized fully at that time. Therefore, spontaneous improvements were attributed to treatment.
Surgical
Various procedures are performed on trigeminal nerve or autonomic pathways, including alcohol injections and section or avulsion of nerves for chronic refractory cases.
Surgery is used if the patient has contraindications to medications or if medications are not effective. Surgery is used in strictly unilateral cases.
Radiofrequency thermocoagulation of trigeminal ganglion has had promising results in some patients with intractable pain.
[Guideline] Biondi D, Mendes P. Treatment of primary headache: cluster headache. In: Standards of care for headache diagnosis and treatment. Chicago (IL): National Headache Foundation. 2004;
