Cluster Headache

	© Michael John Coleman

From Saunders Manual of Neurologic Practice; by Randolph W. Evans, MD, advisor to MAGNUM. The purpose of this section is to supply our members with the latest medical information regarding Cluster Headaches. Although MAGNUM keeps its focus on Migraine disease, cluster is a close cousin, and can exist as a co-morbid condition. MAGNUM is also concerned with ALL headache disorders as well as pain public health issues.

Excerpt from Evans RW, Saunders Manual of Neurologic Practice, Elsevier Science, Phildelphia, 2003, with permission.

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EPIDEMIOLOGY AND RISK FACTORS

1. About 0.4% of the general population
2. Male:female ratio of 5:1
3. 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
4. 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

1. Incompletely understood
2. Genetic factors in some cases
1. Positive family history in 7%.
2. First degree relatives have a 14-fold increased risk of cluster headache
3. Activation of the trigeminovascular system as in migraine may explain the pain
4. Autonomic features due to activation of the cranial parasympathetic fibers
1. Fibers originate from first-order neurons within the superior salivatory nucleus which has a functional brainstem connection to the trigeminal nucleus caudalis
2. These fibers travel with the seventh cranial nerve and synapse in the pterygopalatine ganglia
3. Post-ganglionic fibers provide vasomotor and secretomotor innervation to the cerebral blood vessels and the lacrimal and nasal mucosal glands, respectively
5. A postganglionic Horner’s syndrome during attacks is indicative of involvement of the carotid sympathetic pleux
1. The cavernous carotid artery , where the parasympathetic, sympathetic, and trigeminal fibers converge, is a likely location
6. The circadian, circannual, and seasonal rhythmicity of cluster suggests a periodic disturbance of the suprachiasmatic nucleus of the hypothalamus
1. Hypothalamic abnormalities have been demonstrated in PET scan and morphometric MR imaging studies

CLINICAL FEATURES

1. Periodicity
1. Individual cluster attacks occur during attack phases or cluster periods
2. Most patients have one to two annual cluster periods with each lasting between one and three months
3. Some patients have a seasonal propensity
4. Remission usually last between 6 months to 2 years
5. Circadian periodicity
1. Usually one to two attacks per day although some patients will have up to eight attacks per day
2. In individuals, the attacks usually occur at the same time each day.
1. The most common times of onset are 1-2 am, 1-3 pm, and 9 pm.
2. The nocturnal attacks may correlate with the onset of the first period of rapid eye movement sleep.
2. Symptoms and signs
1. Unilateral severe pain with the most common sites, in order of decreasing frequency, orbital, retroorbital, temporal, supraorbital, and infraorbital.
1. The headache may alternate sides between cluster periods or rarely within the same period.
2. Pain described as constant, boring, pressing, burning, or stabbing and, about 30%, describe throbbing or pulsating
2. 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).
3. 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.
4. Autonomic symptoms are present in over 97%
1. Lacrimation and conjunctival injection are each present in 80%
2. Ipsilateral congestion or clear drainage of the nares present in 75%
3. A partial Horner’s 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
4. Increased forehead sweating may occur in a minority of patients during attacks.
5. Erythema of the eyelid or a circumscribed area of the face or forehead may be present
5. Nausea, light, and noise sensitivity present in some patients. Occasionally, a visual aura may precede the headache.
3. Precipitating factors
1. Small quantities of alcohol can trigger attacks during cluster periods but not during remission
2. Nitroglycerin and histamine can trigger attacks during cluster periods

KEY CLINICAL FEATURES Periodicity 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 Horner’s during headache in 65%

DIFFERENTIAL DIAGNOSIS

1. Symptomatic or secondary cluster headache
1. Can be due to head trauma or iatrogenic trauma (orbital enucleation and dental extraction)
2. 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
1. Include arteriovenous malformations, aneurysms, sphenoid sinusitis, parasellar tumors, upper cervical cord meningioma and infarction, subdural hematoma, cerebral metastases, and temporal arteritis.
2. Cluster headaches can usually be diagnosed based upon the clinical criteria without the need for neuroimaging
3. Neuroimaging , preferably MRI, may be considered for patients with the following:
1. A pattern of clusterlike headache that does not conform to the clinical criteria
2. Onset of cluster headache after age 40
3. A progressive pattern of headaches
4. Chronic cluster headache
5. Any focal neurologic deficit other than Horner’s syndrome

KEY INDICATIONS FOR CONSIDERING NEUROIMAGING Clusterlike headache that does not conform to the clinical criteria Onset of cluster headache after age 40 Progressive pattern of headaches Chronic cluster headache Any focal neurologic deficit other than Horner’s sytndrome

4. 4. Cluster-migraine and cluster-tic
1. Migraine can occur with cluster features such as recurring cluster periods and diurnal periodicity and shorter duration than migraine but without autonomic features or Horner’s associated with cluster.
2. Cluster-tic
1. Cluster and trigeminal neuralgia may be present at the same time in a patient
2. Some patients may have three types of pain attacks: trigeminal neuralgia-like, cluster-like, and neuralgic pain immediately followed by a cluster-like headache.
5. Chronic paroxysmal hemicrania and SUNCT (see chapter brief head and facial pains)

TREATMENT

1. Acute (see chapter migraine for side effects and contraindications)
1. 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 about 70%
1. Oxygen has a cerebral vasoconstrictive effect and reduces calcitonin gene-related peptide release during attacks
2. Sumatriptan 6 mg subcutaneous
1. Effective in 90% of patients for 90% of their attacks
2. Efficacy within 15 minutes in up to 75%
3. There is no tachyphylaxis or rebound effect
4. Intranasal sumatriptan or oral triptans are less efficacious.
3. Intravenous dihydroergotamine (DHE) 1 mg may provide relief in less than 10 minutes. Intramuscular and intranasal administration take longer to work.
1. Triptans and DHE should not be used within 24 hours of each other.
4. Topical 4% lidocaine administered as nose drops may be effective
1. Patients lie supine with the head tilted backwards toward the floor at 30 degrees and turned to the side of the headache.
2. A nasal dropper may be used and the dose (1 mL of 4% lidocaine) may be repeated once after 15 minutes.
5. 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 Triptans DHE Topical 4% lidocaine given as nose drops Butorphanol nasal spray (addiction potential)

2. Transitional treatments
1. Medications which may induce rapid suppression of attacks during the time interval before a preventative is effective.
2. Prednisone 60 mg daily for 3 days then 10 mg decrements every 3 days given in the morning to prevent interference with sleep
3. Ergotamine tartrate 1 mg orally twice a day including a bedtime day if nocturnal attacks occur. Contraindicated in peripheral and cardiovascular disease
4. Ergotamine and triptans should not be used within 24 hours of each other.
5. DHE 0.5- 1.0 mg subcutaneously or intramuscular every 8-12 hours
6. A greater occipital nerve block in the side ipsilateral to the attacks with 120 mg of methylprednisolone and lidocaine may produce a temporary remission
3. Preventative medications (see migraine chapter for information on side effects and contraindications)
1. Verapamil is the drug of choice for episodic and chronic types.
1. 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
2. Baseline and serial electrocardiograms are indicated to monitor for the development of heart block when using dose of 240 mg per day or higher
2. 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.
3. Divalproex sodium (500-2000 mg daily)
4. Lithium carbonate (150-300 mg tid
1. Used more for chronic than episodic cluster
2. Need to closely monitor for side effects
5. Topirimate (50-125 mg per day)
6. Baclofen 10 mg tid
7. Melatonin 10 mg at bedtime
8. 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.
9. For chronic or intractable cases, can use combination therapy.

KEY PREVENTATIVE TREATMENTS Verapamil Methysergide Divalproex sodium Lithium carbonate Topirimate Baclofen

4. Surgical treatment
1. Indications
   1. Total resistance to medical treatment
   2. Strictly unilateral pain
   3. Stable psychological and personality profiles with low addiction potential.
2. Percutaneous radiofrequency retrogasserian rhizotomy
   1. Good to excellent results in 70%
   2. Loss of facial sensation and corneal reflex required
   3. V1 and V2 lesions adequate for orbital pain
   4. A repeat radiofrequency lesion can be made for recurrence which occurs in 20% of patients.
   5. Transient complications include hyperacusis, tinnitus, jaw deviation, chewing, and ice-pick pain
   6. Persistent complications include facial anesthesia/hypesthesia, corneal anesthesia, and occasionally anesthesia dolorosa.
3. Gamma knife radiosurgery to lesion the trigeminal nerve root may be an effective treatment.
4. 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%.

PROGNOSIS

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.

REFERENCES

Bahra A, May A, Goadsby PJ. Cluster headache. A prospective study with diagnostic implications. Neurology 58:354-361, 2002

Evans RW, Mathew NT. Handbook of Headache. Philadelphia, Lippincott-Williams&Wilkins, 2000

Olesen J, Tfelt-Hansen P, Welch KMA. The Headaches. Second Edition. Philadelphia, Lippincott-Williams&Wilkins, 2000

Silberstein SD, Lipton RB, Dalessio DJ. Wolff’s Headache and Other Head Pain, Seventh Edition. New York, Oxford University Press, 2001