388 Cluster Headache
GENETICS: May be inherited in up to 20% of WORKUP
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, last-
ing 15 to 180 minutes, and occurring from once
every other day to eight times a day over a span
of weeks to months. The attacks are associated
with one or more ipsilateral signs and symp-
toms of parasympathetic activation: Conjunctival
injection, lacrimation (Fig. 1), nasal congestion,
rhinorrhea, forehead and facial sweating, miosis,
ptosis, or eyelid edema. Most patients are rest-
less or agitated during an attack.
SYNONYMS
Headache, cluster
Ciliary neuralgia
Erythromelalgia of the head
Erythroprosopalgia of Bing
Horton headache
ICD-10CM CODES
G44.001 Cluster headache syndrome,
unspecified, intractable
G44.009 Cluster headache syndrome,
unspecified, not intractable
G44.011 Episodic cluster headache, intrac-
table
G44.019 Episodic cluster headache, not
intractable
G44.021 Chronic cluster headache, intrac-
table
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
FIG. 1 This 43-year-old man with cluster head-
aches 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 eye-
brow. (From Kaufman DM, et al.: Kaufman’s clinical
neurology for psychiatrists, ed 8, Philadelphia, 2017,
Elsevier.)
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cases, although uncertainty exists over the
mode or modes of inheritance.
PHYSICAL FINDINGS & CLINICAL
PRESENTATION
• Many of the attacks are nocturnal and some
may be provoked by alcohol ingestion.
• During attack: Conjunctival injection, lacri-
mation, nasal congestion, rhinorrhea, facial
sweating, Horner 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 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 patho-
physiology 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 tempo-
ral pain lasting 15 to 180 minutes
• Frequency of every other day to eight per
day; they may cluster seasonally or at a cer-
tain 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. Conjunctival injection and/or lacrimation
2. Nasal congestion and/or rhinorrhea
3. Eyelid edema
4. Forehead and facial sweating
5. Forehead and facial flushing
6. Miosis and/or ptosis
7. Sensation of fullness in the ear
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 yr and are separated
by attack-free intervals lasting at least 1 month.
A diagnosis of chronic cluster headache
requires meeting the criteria for cluster head-
ache plus at least 1 yr 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
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 imag-
ing 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.
• Galcanezumab-gnlm is the first FDA-
approved medication for episodic clus-
ter headache in adults. First approved for
migraine, this injectable medication is a
humanized monoclonal antibody to calcitonin
gene-related peptide (CGRP), blocking its
binding to the CGRP receptor. It reduces the
average number of cluster headaches per
week from baseline compared to placebo.
• In approximately 75% of patients, subcuta-
neous 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 verap­
amil. 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 monitor-
ing and adjustment to maintain therapeutic
serum level of 0.4 to 1 mEq/L. Equally effec-
tive as verapamil, but with more side effects.
• Ergotamine tartrate: 3 to 4 mg/day during
clusters.
 Cluster Headache 389

• Melatonin: 10 mg per night. Evidence is weak DISPOSITION headache is six times more common than the
and comes from scattered case reports.
• Prednisone: 60 mg PO daily for 1 wk fol-
Headache-free periods tend to increase with
increasing age.
chronic form.
• Home oxygen therapy is reasonable for clus- C
lowed by taper; headaches can return dur- ter headache sufferers.
ing taper. REFERRAL
• Greater and lesser occipital nerve blocks, Refractory cluster headaches may require refer-
with the use of local anesthetics including ral to a headache specialist. SUGGESTED READINGS
lidocaine and bupivacaine along with steroids Available at ExpertConsult.com
like Depo-Medrol, dexamethasone, or triam-
cinolone, may be used to shorten the dura- PEARLS &
RELATED CONTENT
tion of the cluster period. Consensus guide- CONSIDERATIONS Cluster Headaches (Patient Information)
lines from the American Headache Society
have been published recently. COMMENTS

• 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.
and Disorders
Diseases
AUTHORS: Michael Pohlen, MD,
• Cluster headaches are divided into episodic Joseph S. Kass, MD, JD, FAAN, and
(attacks lasting up to 1 yr with more than Siddharth Kapoor, MD
1 month pain-free periods) and chronic
(>1 yr without remission). Episodic cluster

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For personal use only. No other uses without permission. Copyright ©2021. Elsevier Inc. All rights reserved.

These proofs may contain color figures. Those figures may print black and white in the final printed book if a color print product has not been planned. The color figures will appear in color
in all electronic versions of this book.
 Cluster Headache 389.e1

SUGGESTED READINGS
Goadsby PJ et al: Trial of galcanezumab in prevention of episodic cluster head-
ache, N Engl J Med 381:132-41, 2019.
Nesbitt AD, Goadsby PJ: Cluster headache, BMJ 344:e2407, 2012.
Weaver Agostoni J: Cluster headache, Am Fam Physician 88(2):122-128, 2013.

Downloaded for FK UMI Makassar (mahasiswafkumi01@gmail.com) at University of Muslim Indonesia from ClinicalKey.com by Elsevier on February 04, 2021.
For personal use only. No other uses without permission. Copyright ©2021. Elsevier Inc. All rights reserved.

These proofs may contain color figures. Those figures may print black and white in the final printed book if a color print product has not been planned. The color figures will appear in color
in all electronic versions of this book.