eMedicine Specialties > Neurology > Headache and Pain
Cluster Headache: Treatment & Medication
Updated: Sep 4, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
Pharmacologic management of cluster headache (CH) may be classified as abortive/symptomatic or preventive/prophylactic. See Medication section for a detailed discussion.
Other agents that have been used to treat CH are olanzapine8 and kudzu.9 Their effectiveness has not been determined.
Surgical Care
- Invasive nerve blocks and ablative neurosurgical procedures (eg, percutaneous radiofrequency, trigeminal gangliorhizolysis, rhizotomy) all have been implemented successfully in cases of refractory CH. Percutaneous radiofrequency ablation may achieve success in 50% of patients, with fair-to-good results in 20% and failure in about 30%. Side effects include facial dysesthesia, corneal sensory loss, and anesthesia dolorosa.
- Gamma-knife radiosurgery has provided a less invasive alternative for pervasive CH.
- Botulinum toxin injections to manage cluster headaches have produced limited success.10
- Greater occipital nerve block may be beneficial in aborting CH.8
- Deep brain stimulation with implantation of stimulating electrodes under stereotactic guidance into the ipsilateral posterior inferior hypothalamus has emerged as a potential option for chronic CH refractory to pharmacological treatment.11,12,13,14 This technique is invasive and is associated with significant risk of complications, including intracranial hemorrhage.15
- Recently, sphenopalatine ganglion stimulation has shown effectiveness in selected patients with chronic CH.16
Medication
The pharmacologic management of CH may be divided into abortive/symptomatic and preventive/prophylactic strategies. Abortive therapy is directed at stopping or reducing the severity of an acute attack, while prophylactic agents are used to reduce the frequency and intensity of individual headache exacerbations. Due to the fleeting, short-lived nature of the attacks, effective prophylactic therapy should be considered the cornerstone of treatment. The prophylactic therapy should start at the onset of a CH cycle and continue until the patient is headache free for at least 2 weeks. The agent then may be tapered slowly to prevent recurrences.Abortive Agents: Oxygen
These agents are administered to abort an attack of CH. Because of the duration of the attacks, they must provide immediate relief.
High-flow oxygen
Inhalation of high-flow, concentrated oxygen extremely effective for aborting CH attack. Precise mechanism of action poorly understood. Effective alternative to ergotamine. Despite immediate availability of oxygen in ED, its widespread use in outpatient setting limited by impracticality.
Adult
6-8 L/min concentrated (100%) oxygen by face mask for no longer than 15 min
Pediatric
Not established
None reported
None reported
Pregnancy
A - Fetal risk not revealed in controlled studies in humans
Precautions
Inspired oxygen concentrations between 50-100% have a substantial risk of lung damage
Abortive Agents: Triptans
These agents may reduce the inflammation associated with migraine headaches.
Zolmitriptan (Zomig, Zomig-ZMT); Intranasal zolmitriptan (Zomig Nasal Spray)
As selective agonists of serotonin 5HT1 receptors in cranial arteries, cause vasoconstriction and reduce inflammation associated with antidromic neuronal transmission in CH. Can reduce severity of headache within 15 min of SC injection. Intranasal form recently introduced in US, offering attractive alternative to self-injections.
Adult
2.5-5 mg PO; repeat after 2 h prn; not to exceed 10 mg/d; 5 mg intranasally prn may repeat in 2 h prn
Nasal spray: Administer 5 mg (as a single puff) intranasally; if headache recurs, may repeat dose after 2 h, not to exceed 10 mg/24 h
Pediatric
Not established
Not to be used on the same day as another ergot derivative or triptan; toxicity increases when administered concomitantly with ergot-containing drugs, selective serotonin reuptake inhibitors, and MAOIs
Documented hypersensitivity; ischemic heart disease; uncontrolled hypertension; use of MAOIs in last 2 wk
Pregnancy
Precautions
May cause facial flushing, numbness, paresthesias, and chest pain of noncardiac origin; significant elevation in blood pressure, including hypertensive crisis, has been reported in patients without history of hypertension; peripheral vascular ischemia, colonic ischemia with abdominal pain, and bloody diarrhea have occurred
Naratriptan (Amerge, Naramig)
As selective agonists of serotonin 5HT1 receptors in cranial arteries, cause vasoconstriction and reduce inflammation associated with antidromic neuronal transmission in CH. Can reduce severity of headache within 15 min of SC injection.
Adult
1-2.5 mg PO q4h prn for headache; not to exceed 5 mg/d
Pediatric
Not established
Oral contraceptives may significantly increase naratriptan concentrations and prolonged vasospastic reactions may occur, avoid concurrent use within 24 h of each other; toxicity may increase when administered concomitantly with ergot-containing drugs, selective serotonin reuptake inhibitors, and MAOIs
Documented hypersensitivity; ischemic heart disease; uncontrolled hypertension; cerebrovascular or peripheral vascular syndromes; severe renal impairment (CrCl < 15 mL/min); severe hepatic impairment (Child-Pugh grade C)
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Chest, jaw or neck tightness may occur after 5-HT1 agonist administration; atypical sensations over precordium (pain, tightness, pressure, heaviness) may occur (rarely associated with arrhythmias or ischemic ECG changes); evaluate patients with signs or symptoms suggestive of angina for presence of CAD or predisposition to Prinzmetal variant angina before receiving additional doses; monitor ECG if dosing resumed and similar symptoms recur
Sumatriptan succinate (Imitrex)
As selective agonists of serotonin 5HT1 receptors in cranial arteries, cause vasoconstriction and reduce inflammation associated with antidromic neuronal transmission in CH. Can reduce severity of headache within 15 min of SC injection. Intranasal form recently introduced in US, offering attractive alternative to self-injections.
Adult
6 mg SC, followed by second injection prn at least 1 h after first; not to exceed 2 injections/d
25-100 mg PO, followed by second dose 2 h later prn; not to exceed 300 mg/d 1 spray (5-20 mg) in 1 nostril or 1 spray (5 mg) in each nostril; may repeat in 2 h prn; not to exceed 40 mg/d
Pediatric
Not established
Toxicity increases when administered concomitantly with ergot-containing drugs, selective serotonin reuptake inhibitors, and MAOIs
Documented hypersensitivity; ischemic heart disease; uncontrolled hypertension
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Hypertensive crisis, coronary artery vasospasm, cardiac arrest, peripheral ischemia, and bloody diarrhea may occur rarely when administering medication
Rizatriptan (Maxalt, Maxalt-MLT)
Selective agonist for serotonin 5-HT1 receptors in cranial arteries and suppresses the inflammation associated with migraine headaches.
Adult
5-10 mg PO q2h prn for headache; not to exceed 30 mg/d
Pediatric
Not established
Toxicity increases when administered concomitantly with ergot-containing drugs, selective serotonin reuptake inhibitors, and MAOIs
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Hypertensive crisis, coronary artery vasospasm, cardiac arrest, peripheral ischemia, bloody diarrhea, and death may occur when administering this medication
Almotriptan (Axert)
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.
Adult
6.25-12.5 mg PO at onset of headache; may repeat once, not to exceed 25 mg/d
Pediatric
<12 years: Not recommended
>12 years: Administer as in adults
Toxicity may increase when used within 24 h of ergotamines or other 5-HT agonists; coadministration with SSRIs may cause weakness, hyperreflexia, or incoordination; CYP450-3A4 inhibitors (eg, ketoconazole, itraconazole, ritonavir, erythromycin) may increase plasma concentration and subsequent toxicity
Documented hypersensitivity; hemiplegic or basilar migraine; ischemic heart disease; uncontrolled hypertension
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Decrease dose and do not exceed 12.5 mg/d in renal or hepatic impairment
Frovatriptan (Frova)
Used to treat acute migraine. Selective 5-HT1B/1D receptor agonist with long half-life of 24 h and low headache recurrence rate within 24-hour period of taking the drug. 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.
Adult
2.5 mg PO once at onset of migraine attack
Pediatric
Not established
Toxicity may increase when used within 24 h of ergotamines or other 5-HT agonists; coadministration with SSRIs may cause weakness, hyperreflexia, or incoordination
Documented hypersensitivity; hemiplegic or basilar migraine; ischemic heart disease; uncontrolled hypertension
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Hypertensive crisis, coronary artery vasospasm, cardiac arrest, peripheral ischemia, bloody diarrhea, and death may occur
Eletriptan (Relpax)
Selective serotonin agonist. Specifically acts at 5-hydroxytryptamine 1B/1D/1F (5-HT1B/1D/1F) receptors on intracranial blood vessels and sensory nerve endings to relieve pain associated with acute headaches.
Adult
20-40 mg/dose PO at onset of headache; if initial dose ineffective, may repeat dose once after 2 h; not to exceed 80 mg/d
Pediatric
<18 years: Not established
Potent CYP450 3A4 inhibitors (eg, ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir) may increase toxicity; concurrent administration with ergot-containing drugs may increase vasospastic reactions
Documented hypersensitivity; severe hepatic impairment; age >65 y; administration within 72 h of potent CYP450 3A4 inhibitors
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Patients with known or suspected coronary artery disease may have increased risk of myocardial ischemia, infarction, or other cardiac or cerebrovascular events (5-HT1 agonists may cause coronary vasospasm)
Abortive Agents: Ergot Alkaloids
These agents are highly effective in relieving acute CH pain.
Dihydroergotamine (D.H.E. 45 injection, Migranal)
Available in IV or intranasal preparations, tends to cause less arterial vasoconstriction than ergotamine tartrate.
Adult
Up to 2 mg IV; not to exceed 2 mg/dose or 6 mg/wk 1 mg IM/SC at first sign of onset; not to exceed 3 mg total 1 spray (0.5 mg) into each nostril; not to exceed 6 sprays/d or 8 sprays/wk
Pediatric
Not established
May increase effects of heparin; erythromycin, clarithromycin, nitroglycerin, propranolol, and troleandomycin may increase toxicity
Documented hypersensitivity; within 24 h of sumatriptan, zolmitriptan, other serotonin agonists, or ergotlike agents; use of MAOIs within last 2 wk
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Use caution in patients with hypertension, angina, peripheral vascular disease, or impaired renal or hepatic function
Ergotamine (Cafatine, Cafergot, Cafetrate, Ercaf)
Vasoconstrictor of smooth muscle in cranial blood vessels, alpha-adrenergic blocker, and nonselective 5-HT agonist. PR or SL preparations of ergotamine tartrate preferred to PO because of immediate onset of action. Avoid exceeding maximum dosage guidelines to prevent rebound headaches.
Adult
2 tabs PO at first sign of onset, followed by 1 tab q30min prn; not to exceed 6 tabs/attack or 10 tabs/wk 1 tab SL at first sign of onset, followed by 1 tab q30min prn; not to exceed 3 tabs/24h or 5 tabs/wk 1 supp PR at first sign of onset, followed by second dose prn after 1 h; not to exceed 2 supp/attack or 5 supp/wk
Pediatric
Not established
Erythromycin, troleandomycin, and other macrolide antibiotics may increase toxicity
Documented hypersensitivity
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Use caution in patients with history of hypertension or coronary or peripheral arterial insufficiency; use caution in elderly persons, as may precipitate angina or MI or aggravate intermittent claudication; avoid prolonged administration or excessive dosage, since increases danger of ergotism or gangrene; patients who take for extended periods may become dependent
Abortive Agents: Anesthetics
Local anesthetics stabilize the neuronal membrane so the neuron is less permeable to ions. This prevents initiation and transmission of nerve impulses, thereby producing the local anesthetic action.
Intranasal lidocaine 4% (Xylocaine)
An experimental abortive therapy in CH, blocks conduction of nerve impulses by decreasing neuronal membrane's permeability of sodium ions, which results in inhibition of depolarization and blockade of conduction. Effective in 2 separate clinical trials. Intranasal administration of lidocaine drops requires specific and, for many patients, difficult technique.
Adult
4% solution intranasally; actual dose not established
Pediatric
Not established
May enhance effects of succinylcholine
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Use extreme caution in patients with marked hypoxia, severe respiratory depression, or bradycardia
Oral Opioids and Other Analgesics
The short-lived and unpredictable character of CH precludes the effective use of oral narcotics or analgesics. Despite their lack of efficacy, these substances are abused by some CH sufferers.
Narcotics are not recommended in aborting cluster headaches.
Intranasal capsaicin
This experimental therapy successfully tested in clinical trials. Derived from chili peppers, induces release of substance P, principal chemomediator of pain impulses from periphery to CNS. After repeated applications, depletes neuron of substance P and prevents reaccumulation.
Adult
Few drops of capsaicin solution applied to ipsilateral nostril
Pediatric
Not established
None reported
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Avoid contact with eyes; irritant to mucosal membranes, should be used with caution; warn patients about nasal cavity irritation, burning, congestion, drainage, and sneezing while using
Prophylactic Agents: Calcium Channel Blockers
These agents inhibit the initial vasoconstrictive phase of CH.
Verapamil (Calan, Verelan, Covera-HS)
Perhaps most effective calcium channel blocker for CH prophylaxis, inhibits calcium ions from entering slow channels, select voltage-sensitive areas, or vascular smooth muscle, thereby producing vasodilation.
Adult
Immediate release: 120-360 mg/d PO divided tid/qid
Extended release form may be given qd
Pediatric
Not established
Phenobarbital, hydantoins, vitamin D, sulfinpyrazone, and rifampin may decrease serum concentrations by increasing hepatic metabolism; amiodarone may increase toxicity; beta blockers may increase cardiac depressant effects on AV conduction; cimetidine may increase serum levels; may increase cyclosporine, doxorubicin, theophylline, carbamazepine, vecuronium, and digoxin serum levels
Documented hypersensitivity; sinus bradycardia; cardiogenic shock; advanced heart block; ventricular tachycardia; congestive heart failure; atrial fibrillation or flutter associated with accessory conduction pathways
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Use caution in patients with sick-sinus syndrome, severe left ventricular dysfunction, hepatic or renal impairment, or hypertrophic cardiomyopathy; monitor ECG and blood pressure closely in patients with supraventricular tachycardia receiving IV therapy; adverse effects include constipation and water retention; patients intolerant of verapamil should try nimodipine, diltiazem, or nifedipine
Prophylactic Agents: Mood Stabilizers
Mechanism of action of lithium in CH is unclear, although preliminary evidence suggests that it may interfere with substance P and vasoactive intestinal peptide–induced arterial relaxation.
Lithium carbonate (Eskalith, Lithane, Lithobid, Lithonate, Lithotabs)
Effectively prevents CH (particularly in its more chronic forms) and treats bipolar mood disorder, another cyclic illness. Responses variable, but still recommended first-line agent in CH. Narrow therapeutic window requires close monitoring of levels and adverse effects. Plasma lithium level of 0.6-1.2 mEq/L measured at steady state, 12 h after last dose (ie, just before next dose), usually sought, but optimal plasma levels for prevention of CH not established. Thought effective in CH at serum concentrations lower than those required in bipolar disorder (0.3-0.8 mEq/L).
Adult
600-900 mg/d PO in divided doses; increase to 600-1200 mg/d divided bid/qid prn
Pediatric
Not established
Thiazide diuretics, NSAIDs, haloperidol, phenothiazines, neuromuscular blockers, carbamazepine, fluoxetine, and ACE inhibitors may increase serum levels and toxicity; theophylline, caffeine, and other xanthines decrease effects
Documented hypersensitivity; severe cardiovascular or renal disease
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Lithium toxicity can occur at therapeutic doses; use caution in patients with cardiovascular or thyroid disease, severe debilitation, dehydration, or sodium depletion, or in patients taking diuretics; adverse effects include tremor, polyuria, diarrhea, nausea, fatigue, weight gain, and thyroid dysfunction; renal toxicity with tubular damage and interstitial fibrosis may occur; CNS toxicity manifested by confusion and ataxia
Prophylactic Agents: Anticonvulsants
Efficacy in the prophylaxis of CH has been demonstrated in a few relatively small controlled studies. Unclear mechanism of action for the prevention of CH. May act by regulating central sensitization.
Divalproex sodium (Depakene, Depakote)
Few adequate studies available, with mixed results.
Adult
Typically started at 500 mg PO qd; may titrate up to 3,000 mg/d (bid dosing for doses >1,500 mg)
Pediatric
Not established
Coadministration with cimetidine, salicylates, felbamate, and erythromycin may increase toxicity; rifampin may significantly reduce valproate levels; in pediatric patients, protein binding and metabolism of valproate decrease when taken concomitantly with salicylates; coadministration with carbamazepine may result in variable changes of carbamazepine concentrations with possible loss of seizure control; valproate may increase diazepam and ethosuximide toxicity (monitor closely); valproate may increase phenobarbital and phenytoin levels while either one may decrease valproate levels; valproate may displace warfarin from protein binding sites (monitor coagulation tests); may increase zidovudine levels in HIV seropositive patients
Documented hypersensitivity; liver impairment; urea cycle disorders; pregnancy (high risk of teratogenesis)
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Should be used with caution in patients with renal insufficiency, in elderly patients, and in patients with bleeding diathesis
Topiramate (Topamax)
Effective in several small prospective studies. Exact mechanism of action in CH headache unknown.
Adult
Typically started at 25 mg qhs; titrate up very slowly by 25-mg weekly increments to a bid dosing; target dose should be 100-200 mg/d
Pediatric
Not established
May increase phenytoin levels; use with ethosuximide may augment risk for CNS depression; may reduce effectiveness of estrogen-containing contraceptives; concomitant use with carbonic anhydrase inhibitors may increase risk of nephrolithiasis
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in patients with history of nephrolithiasis; caution in severe dehydration or diarrhea
Corticosteroids
These agents are extremely effective in terminating a CH cycle and in preventing immediate headache recurrence. High-dose prednisone is prescribed for the first few days, followed by a gradual taper. The simultaneous use of standard prophylactic agents (eg, verapamil) is recommended. The mechanism of action in CH is still subject to speculation.
Prednisone (Sterapred)
Very effective in aborting CH cycle or as intermediate prophylaxis (bridging therapy between acute and prophylactic agents). Effective for treatment of CH not responsive to lithium or methysergide. Effects in CH may occur via inhibition of prostaglandin synthesis. Long-term use not recommended.
Adult
40-60 mg/d PO in divided doses for 5 d, followed by slow taper over 2-4 wk
Pediatric
Not established
Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Documented hypersensitivity; systemic fungal infections or serious infections, except septic shock or tuberculous meningitis
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Use cautiously in patients with diabetes, hypothyroidism, cirrhosis, congestive heart failure, thromboembolic disorders, or ulcerative colitis; chronic use may lead to gastric ulceration, immunosuppression, electrolyte disturbances, weight gain, and osteopenia
Methysergide (Sansert)
Useful in patients unresponsive to lithium. Although of ergotamine chemical class, actions differ, since has minimal ergotaminelike vasoconstrictive properties and significantly greater serotoninlike properties. Very effective in episodic and chronic CH prophylaxis. Often effective in reducing pain frequency, particularly in younger patients with episodic CH. If no improvement after 3 wk, unlikely to be beneficial. Do not give continuously for > 6 mo. Drug-free interval of 3-4 wk must follow each 6-mo course. Product no longer available in the United States.
Adult
2-8 mg/d PO
Pediatric
Not established
None reported
Documented hypersensitivity; peripheral vascular disease; severe arteriosclerosis; pulmonary disease; severe hypertension; phlebitis; serious infections
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Use > 6 mo discouraged, because long-term therapy may cause retroperitoneal fibrosis and fibrotic thickening of cardiac valves (drug holiday recommended to avoid these effects); adverse GI reactions most commonly affect compliance; use caution in renal or hepatic impairment; adverse effects include leg cramps, paresthesias, edema, and skin discoloration
More on Cluster Headache |
| Overview: Cluster Headache |
| Differential Diagnoses & Workup: Cluster Headache |
 Treatment & Medication: Cluster Headache |
| Follow-up: Cluster Headache |
| References |
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Further Reading
Keywords
cluster headache, CH, Bing-Horton syndrome, histaminic cephalalgia, cluster migraine, paroxysmal nocturnal cephalalgia, red migraine, erythromelalgia of the head, sphenopalatine neuralgia, migrainous neuralgia, periorbital pain, Horton’s headache
