Cluster Headache

Michael Pohlen, M.D.
Joseph S. Kass, M.D., J.D.
Siddharth Kapoor, M.D.

Basic Information

Definition

The term cluster headache refers to attacks of severe, unilateral pain that is orbital, supraorbital, temporal, or any combination of these sites, lasting 15 to 180 minutes, and occurring from once every other day to eight times a day. The attacks are associated with one or more ipsilateral signs and symptoms of parasympathetic activation: conjunctival injection, lacrimation (Fig. 1), nasal congestion, rhinorrhea, forehead and facial sweating, miosis, ptosis, or eyelid edema. Most patients are restless or agitated during an attack.

FIG.1

This 43-year-old man with cluster headaches suffers from nightly right-sided unrelenting, severe, stabbing unilateral periorbital pain for 45 minutes to 3 hours accompanied by ipsilateral tearing and nasal discharge, along with ptosis and miosis (a partial Horner syndrome). Note that the ptosis prompts compensatory elevation of the eyebrow.

From Kaufman DM, et al.: *Kaufman’s clinical neurology for psychiatrists*, ed 8, Philadelphia, 2017, Elsevier.

Synonyms

Headache, cluster
Ciliary neuralgia
Erythromelalgia of the head
Erythroprosopalgia of Bing
Horton’s headache

ICD-10CM CODES
G44.001	Cluster headache syndrome, unspecified, intractable
G44.009	Cluster headache syndrome, unspecified, not intractable
G44.011	Episodic cluster headache, intractable
G44.019	Episodic cluster headache, not intractable
G44.021	Chronic cluster headache, intractable
G44.029	Chronic cluster headache, not intractable

Epidemiology & Demographics

Incidence

Estimated to occur in 0.05% to 1% of the population

Predominant Sex

Occurs in males at least five times more commonly than in females

Predominant Age

Peak age of onset between 20 and 40 yr

Genetics

May be inherited in up to 20% of cases, although uncertainty exists over the mode or modes of inheritance.

Physical Findings & Clinical Presentation

•

During attack: conjunctival injection, lacrimation, nasal congestion, rhinorrhea, facial sweating, Horner’s syndrome.
•

In contrast to migraine sufferers, patients are agitated and active during an attack.
•

Symptoms associated with an attack remain ipsilateral during the attack but may switch sides from one attack to the next.
•

Permanent partial Horner’s syndrome in 5% of patients; otherwise examination is normal.

Etiology

Activation of the posterior hypothalamic gray matter resulting in trigeminal activation coupled with parasympathetic activation. The pathophysiology remains controversial.

Diagnosis

Per the International Classification of Headache Disorders, 3rd edition, the diagnosis of cluster headache requires all of the following:

•

At least five attacks of severe or very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15 to 180 minutes.
•

Frequency of every other day to eight per day; they may cluster seasonally or at a certain time in a patient’s life.
•
Headache is accompanied by a sense of restlessness or agitation and/or at least one of the following (ipsilateral):
1. 1.
  
  Conjunctival injection and/or lacrimation
2. 2.
  
  Nasal congestion and/or rhinorrhea
3. 3.
  
  Eyelid edema
4. 4.
  
  Forehead and facial sweating
5. 5.
  
  Forehead and facial flushing
6. 6.
  
  Miosis and/or ptosis
7. 7.
  
  Sensation of fullness in the ear
8. 8.
  
  Restlessness or agitation

A diagnosis of episodic cluster headache requires the above criteria plus attacks that occur in bouts, also called cluster periods. These periods last 1 week to 1 year and are separated by attack-free intervals lasting at least 1 month.

A diagnosis of chronic cluster headache requires meeting the criteria for cluster headache plus at least 1 year of attacks without a pain-free interval of at least 1 month.

Differential Diagnosis

•

Migraine
•

Trigeminal neuralgia
•

Primary stabbing headache
•

Temporal arteritis
•

Post-herpetic neuralgia
•

Venous sinus thrombosis
•

Carotid-cavernous fistula or other cavernous sinus lesions
•

Other trigeminal autonomic cephalalgias
•

Section II describes the differential diagnosis of headaches

Workup

Diagnosis is made clinically.

Imaging Studies

•

None, unless history or examination suggests focal neurologic deficit or headaches change in character or are of new onset.
•

MRI of the brain along with vascular imaging may be necessary to exclude secondary headaches at the time of initial diagnosis.

Treatment

Nonpharmacologic Therapy

Avoidance of alcohol, histamine, nitroglycerin, and tobacco during clusters

Abortive Rx

•

Inhalation of 100% oxygen by face mask at a flow rate of 12 L/min or greater for 15 min aborts the attack in 60% to 80% of patients.
•

In approximately 75% of patients, subcutaneous or nasal triptans (e.g., sumatriptan, zolmitriptan) will result in freedom from pain within 20 minutes. Only injectable and nasal formulations achieve a response that is rapid enough to be efficacious.
•

Cafergot, octreotide, intranasal lidocaine, or dihydroergotamine may abort an attack or prevent one if given just before a predictable episode. An attack typically resolves before oral analgesics can take effect, although indomethacin and other NSAIDs may be effective in prolonged attacks.

Prophylaxis Rx

For patients with episodic cluster headache, prophylactic treatment should be started at the onset of the cluster period and tapered at its end. Patients with chronic cluster headache should be started on prophylactic treatment at increasing doses until good control is achieved. Preventative therapy should begin with verapamil. Alternative treatment options are also listed below.

•

Verapamil: Start at 240 mg/day; increase up to 960 mg/day as tolerated. Dosing three times per day may be more effective than extended release. First-degree AV block may develop with escalating doses, so ECG should be checked.
•

Topiramate: up to 50 mg bid; can be used as add-on to verapamil.
•

Lithium: 200 mg tid with frequent monitoring and adjustment to maintain therapeutic serum level of 0.4 to 1 mEq/L. Equally effective as verapamil, but with more side effects.
•

Ergotamine tartrate: 3 to 4 mg/day during clusters.
•

Melatonin: 10 mg per night. Evidence is weak and comes from scattered case reports.
•

Prednisone: 60 mg PO daily for 1 wk followed by taper; headaches can return during taper.
•

Greater and lesser occipital nerve blocks, with the use of local anesthetics including lidocaine and bupivacaine along with steroids like Depo-Medrol, dexamethasone, or triamcinolone, may be used to shorten the duration of the cluster period. Consensus guidelines from the American Headache Society have been published recently.
•

There is emerging evidence for benefit of a sphenopalatine ganglion block that may be available at some centers for both treatment and prophylaxis of cluster attacks.

Disposition

Headache-free periods tend to increase with increasing age.

Referral

Refractory cluster headaches may require referral to a headache specialist.

Pearls & Considerations

Comments

•

Cluster headaches are divided into episodic (attacks lasting up to 1 year with more than 1 month pain-free periods) and chronic (>1 year without remission). Episodic cluster headache is six times more common than the chronic form.
•

Home oxygen therapy is reasonable for cluster headache sufferers.

Ferri – Cluster Headache