|This section is written for doctors, but will give a
better understanding to sufferers and laypersons as well. In addition,
it may help many to formulate questions to take to their physicians at
their next visit to the doctorﾕs office. To our members in the
medical community, we hope this section addresses some of your questions
regarding cluster headaches.
Excerpt from Evans RW, Saunders Manual of
Neurologic Practice, Elsevier
Science, Phildelphia, 2003, with permission.
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EPIDEMIOLOGY AND RISK FACTORS
- About 0.4% of the general population
- Male:female ratio of 5:1
- Can occur at any age including childhood and
adolescence (rare before the age of 10) but usually begins in the
third or fourth decade of life
- 90% have episodic cluster and 10% chronic (cluster
period lasts for more than one year without remission or remission
lasts less than 14 days).
ETIOLOGY AND PATHOPHYSIOLOGY
- Incompletely understood
- Genetic factors in some cases
- Positive family history in 7%.
- First degree relatives have a 14-fold increased
risk of cluster headache
- Activation of the trigeminovascular system as
in migraine may explain the pain
- Autonomic features due to activation of the
cranial parasympathetic fibers
- Fibers originate from first-order neurons within
the superior salivatory nucleus which has a functional brainstem
connection to the trigeminal nucleus caudalis
- These fibers travel with the seventh cranial
nerve and synapse in the pterygopalatine ganglia
- Post-ganglionic fibers provide vasomotor and
secretomotor innervation to the cerebral blood vessels and the lacrimal
and nasal mucosal glands, respectively
- A postganglionic Horners syndrome during
attacks is indicative of involvement of the carotid sympathetic pleux
- The cavernous carotid artery , where the parasympathetic,
sympathetic, and trigeminal fibers converge, is a likely location
- The circadian, circannual, and seasonal rhythmicity
of cluster suggests a periodic disturbance of the suprachiasmatic
nucleus of the hypothalamus
- Hypothalamic abnormalities have been demonstrated
in PET scan and morphometric MR imaging studies
- Individual cluster attacks occur during attack
phases or cluster periods
- Most patients have one to two annual cluster
periods with each lasting between one and three months
- Some patients have a seasonal propensity
- Remission usually last between 6 months to
- Circadian periodicity
- Usually one to two attacks per day although
some patients will have up to eight attacks per day
- In individuals, the attacks usually occur
at the same time each day.
- The most common times of onset are 1-2
am, 1-3 pm, and 9 pm.
- The nocturnal attacks may correlate with
the onset of the first period of rapid eye movement sleep.
- Symptoms and signs
- Unilateral severe pain with the most common
sites, in order of decreasing frequency, orbital, retroorbital,
temporal, supraorbital, and infraorbital.
- The headache may alternate sides between
cluster periods or rarely within the same period.
- Pain described as constant, boring, pressing,
burning, or stabbing and, about 30%, describe throbbing or pulsating
- There is a rapid onset of 5-15 minutes and
usually short duration of 30-45 minutes although a minority may
have pain persisting up to 3 hours (and rarely longer).
- During attacks, most patients prefer to walk,
sit, kneel, stand, or jogging in place. Many find it difficult to
lie down and feel restless and agitated.
- Autonomic symptoms are present in over 97%
- Lacrimation and conjunctival injection are
each present in 80%
- Ipsilateral congestion or clear drainage
of the nares present in 75%
- A partial Horners syndrome with a slight
ipsilateral ptosis or miosis or a combination of both is present
in about 65% of cases and may persist between attacks in later
stages of the disorder in some patients
- Increased forehead sweating may occur in
a minority of patients during attacks.
- Erythema of the eyelid or a circumscribed
area of the face or forehead may be present
- Nausea, light, and noise sensitivity present
in some patients. Occasionally, a visual aura may precede the headache.
- Precipitating factors
- Small quantities of alcohol can trigger attacks
during cluster periods but not during remission
- Nitroglycerin and histamine can trigger attacks
during cluster periods
KEY CLINICAL FEATURES
- Unilateral severe pain
- Usually 30-45 minutes but up to 3 hours duration
- Ipsilateral lacrimation and conjunctival injection in 80%
- Ipsilateral congestion or clear nares drainage in 75%
- Partial Horners during headache in 65%
- Symptomatic or secondary
- Can be due to head trauma or iatrogenic trauma
(orbital enucleation and dental extraction)
- A variety of pathologists have been associated
with cluster-like headaches which are usually atypical because of
the lack of periodicity or response to medications or the presence
of abnormal neurological signs
- Include arteriovenous malformations, aneurysms,
sphenoid sinusitis, parasellar tumors, upper cervical cord meningioma
and infarction, subdural hematoma, cerebral metastases, and temporal
- Cluster headaches can usually be diagnosed based
upon the clinical criteria without the need for neuroimaging
- Neuroimaging , preferably MRI, may be considered
for patients with the following:
- A pattern of clusterlike headache that does
not conform to the clinical criteria
- Onset of cluster headache after age 40
- A progressive pattern of headaches
- Chronic cluster headache
- Any focal neurologic deficit other than Horners
KEY INDICATIONS FOR CONSIDERING NEUROIMAGING
- Clusterlike headache that does not conform to the clinical
- Onset of cluster headache after age 40
- Progressive pattern of headaches
- Chronic cluster headache
- Any focal neurologic deficit other than Horners sytndrome
- 4. Cluster-migraine and cluster-tic
- Migraine can occur with cluster features such
as recurring cluster periods and diurnal periodicity and shorter
duration than migraine but without autonomic features or Horners
associated with cluster.
- Cluster and trigeminal neuralgia may be present
at the same time in a patient
- Some patients may have three types of pain
attacks: trigeminal neuralgia-like, cluster-like, and neuralgic
pain immediately followed by a cluster-like headache.
- Chronic paroxysmal hemicrania and SUNCT (see
chapter brief head and facial pains)
- Acute (see chapter migraine for side effects
- Inhalation of 100% oxygen at a rate of 7-10 liters/minute
for 15-20 minutes with a loosely applied face mask is effective in
- Oxygen has a cerebral vasoconstrictive effect
and reduces calcitonin gene-related peptide release during attacks
- Sumatriptan 6 mg subcutaneous
- Effective in 90% of patients for 90% of their
- Efficacy within 15 minutes in up to 75%
- There is no tachyphylaxis or rebound effect
- Intranasal sumatriptan or oral triptans are less
- Intravenous dihydroergotamine (DHE) 1 mg may
provide relief in less than 10 minutes. Intramuscular and intranasal
administration take longer to work.
- Triptans and DHE should not be used within 24
hours of each other.
- Topical 4% lidocaine administered as nose drops
may be effective
- Patients lie supine with the head tilted backwards
toward the floor at 30 degrees and turned to the side of the headache.
- A nasal dropper may be used and the dose (1 mL
of 4% lidocaine) may be repeated once after 15 minutes.
- Butorphanol nasal spray might be tried if other
treatments are not effective or are contraindicated. There is a significant
potential for habituation and addiction.
KEY ACUTE TREATMENTS
- Inhalation of 100% oxygen
- Topical 4% lidocaine given as nose drops
- Butorphanol nasal spray (addiction potential)
- Transitional treatments
- Medications which may induce rapid suppression
of attacks during the time interval before a preventative is effective.
- Prednisone 60 mg daily for 3 days then 10 mg
decrements every 3 days given in the morning to prevent interference
- Ergotamine tartrate 1 mg orally twice a day including
a bedtime day if nocturnal attacks occur. Contraindicated in peripheral
and cardiovascular disease
- Ergotamine and triptans should not be used within
24 hours of each other.
- DHE 0.5- 1.0 mg subcutaneously or intramuscular
every 8-12 hours
- A greater occipital nerve block in the side ipsilateral
to the attacks with 120 mg of methylprednisolone and lidocaine may
produce a temporary remission
- Preventative medications (see migraine chapter
for information on side effects and contraindications)
- Verapamil is the drug of choice for episodic
and chronic types.
- Total daily dose starting at 120 240 mg
in three divided doses slowly increasing up to 480 mg. Doses up to
1200 mg per day have been used in chronic cluster headache
- Baseline and serial electrocardiograms are indicated
to monitor for the development of heart block when using dose of 240
mg per day or higher
- Methysergide for younger patients without contraindications
for episodic cluster ( 2 mg tid up to 12 mg daily). May be best to
avoid combining with ergotamine, DHE, or triptans because of potential
for additive vasoconstrictor effect.
- Divalproex sodium (500-2000 mg daily)
- Lithium carbonate (150-300 mg tid
- Used more for chronic than episodic cluster
- Need to closely monitor for side effects
- Topirimate (50-125 mg per day)
- Baclofen 10 mg tid
- Melatonin 10 mg at bedtime
- Topical capsaicin 0.025% cream applied via a
cotton-tipped applicator 0.5 inch up the nostril ipsilateral to the
side of the headache three times daily for 7 days might be effective.
- For chronic or intractable cases, can use combination
KEY PREVENTATIVE TREATMENTS
- Surgical treatment
- Total resistance to medical treatment
- Strictly unilateral pain
- Stable psychological and personality profiles
with low addiction potential.
- Percutaneous radiofrequency retrogasserian
- Good to excellent results in 70%
- Loss of facial sensation and corneal reflex
- V1 and V2 lesions adequate for orbital
- A repeat radiofrequency lesion can be made
for recurrence which occurs in 20% of patients.
- Transient complications include hyperacusis,
tinnitus, jaw deviation, chewing, and ice-pick pain
- Persistent complications include facial
anesthesia/hypesthesia, corneal anesthesia, and occasionally
- Gamma knife radiosurgery to lesion the trigeminal
nerve root may be an effective treatment.
- Percutaneous retrogasserian glycerol rhizolysis
may also be an effective treatment with much less risk for corneal
anesthesia or facial anesthesia compared to radiofrequency surgery.
The recurrence rate is about 40%.
About 20% of patients with episodic cluster can
evolve into a chronic pattern
About 30% of patients with the chronic type can
develop episodic cluster with remission periods.
Most patients will develop longer remission periods
with increasing age.
Bahra A, May A, Goadsby PJ. Cluster headache. A
prospective study with diagnostic implications. Neurology 58:354-361,
Evans RW, Mathew NT. Handbook of Headache. Philadelphia,
Olesen J, Tfelt-Hansen P, Welch KMA. The Headaches.
Second Edition. Philadelphia, Lippincott-Williams&Wilkins, 2000
Silberstein SD, Lipton RB, Dalessio DJ. Wolffs
Headache and Other Head Pain, Seventh Edition. New York, Oxford University