II. Pathophysiology

  1. Migraine Variant
  2. Postulated mechanisms
    1. Vascular dilation
    2. Trigeminal Nerve stimulation
    3. Circadian rhythm association (onset of Cluster Headaches often occurs during sleep)

III. Types: Trigeminal Autonomic Cephalalgia

  1. Cluster Headache
    1. Episodic (90%)
      1. At least 2 cluster periods each lasting one week or more (but less than one year)
      2. Remission periods last at least one month
    2. Chronic (10%)
      1. Headaches occur for more than one year
      2. Remissions last <1 month
  2. Cluster Headache Variants
    1. Short-Lasting Unilateral Neuralgiform Headache Attacks with Conjunctival Injection or Tearing (SUNCT Headache)
      1. Very brief (<4 minute) recurrent cluster-like Headaches
    2. Paroxysmal Hemicrania
      1. Brief cluster-like Headaches <30 minutes relieved with Indomethacin
    3. Hemicrania Continua
      1. Continuous cluster-like Headache relieved with Indomethacin

IV. Epidemiology

  1. Uncommon Headache type
    1. Contrast with the much more common Primary Headaches (i.e. Migraine Headache, Tension Headache)
    2. Prevalence of episodic Cluster Headache
      1. Lifetime: 1 in 1000
      2. One year: 53 per 100,000
  2. Much more common in men
    1. Episodic Cluster Headache: 4 to 1 male to female ratio
    2. Chronic Cluster Headache: 15 to 1 male to female ratio
  3. Age of onset
    1. Male: 20 to 40 years old
    2. Female: Onset peaks in 60s (especially in black women)
  4. Hereditary
    1. Autosomal Dominant inheritance pattern in 5% of Cluster Headache patients
    2. First degree relative with Cluster Headache confers up to a nearly 40 fold increase in Cluster Headache risk
    3. Associated with the HCRTR2 gene

V. Risk Factors

VI. Symptoms

  1. Characteristics
    1. Deep pain
    2. Burning, stabbing, or lancinating type pain
  2. Severity
    1. Excruciating pain
    2. Patient may even consider Suicide (hence the common name, "Suicide Headache")
  3. Location
    1. Unilateral Headache typically behind one eye
    2. May be orbital, supraorbital or temporal pain
    3. Radiates to upper teeth, jaw or neck
  4. Timing
    1. At least 5 attacks within 10 days
    2. Occurs from every other day to as often as multiple daily episodes up to 8 per day
    3. Headaches last 15 to 180 minutes
    4. Usually recur at same time of day each day
    5. May awaken patient from sleep (esp. onset of REM)
    6. Recurrence over >1 year without remission of >1 month
      1. However, in those meeting initial criteria for Cluster Headaches, later remissions may last for months to years
  5. Triggers
    1. Sleep Apnea
    2. Vasodilators
      1. Nitroglycerin
      2. Alcohol
      3. Histamine
  6. Associated with at least one of the following
    1. Lacrimation
    2. Ipsilateral forehead or facial Flushing or sweating
    3. Ipsilateral Nasal Discharge
    4. Affected eye red with dilated Conjunctival vessels (Conjunctival injection)
    5. Restlessness, pacing or rocking head in hands
    6. Horner's Syndrome (30% of cases)
      1. Ipsilateral Ptosis
      2. Ipsilateral pupillary constriction (Miosis)

VII. Evaluation

VIII. Imaging

  1. MRI Brain with and without contrast
    1. Recommended for all Trigeminal Autonomic Cephalalgia including Cluster Headaches
    2. Obtain even if no other Headache Red Flag present

IX. Diagnosis

  1. Characteristics: Five or more Headaches meeting the following criteria
    1. Severe to very severe unilateral orbital, supraorbital or temporal pain lasting 15-180 minutes if untreated
    2. Headaches occur from every other day to eight times daily
    3. Headache with at least one of the following ipsilateral autonomic symptoms
      1. Conjunctival injection or Lacrimation
      2. Nasal congestion or Rhinorrhea
      3. Eyelid Edema
      4. Forehead and facial sweating
      5. Miosis or Ptosis
      6. Restlessness or Agitation
  2. Timing
    1. Episodic Cluster Headache
      1. Two or more cluster periods lasting 7-365 days and separated by pain-free remissions >3 month
    2. Chronic Cluster Headache
      1. Episodes recur for more than 1 year without remission or with remission <3 month
  3. References
    1. (2018) Cephalgia 38(1):1-211 [PubMed]

X. Differential Diagnosis

  1. Migraine Headache
    1. Common features do not distinguish from cluster
      1. Aura occurs in 14% of Cluster Headaches
      2. Photophobia occurs in >50% of Cluster Headaches
  2. Hemicrania Continua (or Paroxysmal Hemicrania)
    1. Cluster-type Headache with brief duration (2-30 minutes)
    2. More common in women ages 30-40 years old
    3. Responds well to Indomethacin
  3. Brief Neuralgiform Headache with Conjunctivitis
    1. Unilateral Headache with Conjunctival injection and tearing
    2. Episodes last <4 minutes with recurrence from 3 to 200 times daily
    3. More common in men ages 35 to 65 years old
    4. Refractory to most Headache treatment strategies
  4. Orbital Myositis
    1. Similar to Cluster Headache with longer duration
  5. Tension Headache
  6. Trigeminal Neuralgia

XI. Management: Nonpharmacologic measures

  1. Relaxation Techniques
  2. Cognitive-behavior therapy
  3. Treat comorbid Mood Disorders
  4. Tobacco Cessation
  5. Alcohol cessation

XII. Management: Abortive Treatment for Acute Cluster Headache

  1. See Migraine Treatment
  2. First line agents
    1. Triptan Agents
      1. Sumatriptan (Imitrex)
        1. Intranasal 20 mg (may repeat once in 24 hours)
        2. Subcutaneous: 6 mg SC (may repeat once after 1 hour)
          1. Significant pain relief with 6 mg dose in 75% of patients by 15 minutes (NNT 2.4)
          2. Higher dose (12 mg) adds adverse effects without additional benefit
      2. Zolmitriptan
        1. Oral: 5 mg orally (may repeat once in 24 hours)
        2. Intranasal 10 mg (two sprays of the 5 mg Inhaler)
          1. Significant pain relief in 63% of patients by 30 minutes (NNT 2.8)
    2. Oxygen Inhalation
      1. Apply 100% via nonrebreather Face Mask at 12-15 Liters per minute for 15-20 minutes
      2. Complete relief in 78% of patients
      3. Cohen (2009) JAMA 302(22): 2451-7 [PubMed]
  3. Second-line agents
    1. Intranasal Lidocaine 4-10% solution
      1. Dose: 1 ml intranasally
        1. Aplied with cotton swab bilaterally for 5 minutes
      2. May be repeated twice in 15 minutes prn
      3. Relieves pain within 5-15 minutes
      4. Costa (2000) Cephalalgia 20:85-91 [PubMed]
    2. Indomethacin
      1. Dose: 25-50 mg tid prn
      2. Effective in Hemicrania Continua (or Paroxysmal Hemicrania)
      3. May have delayed benefit
      4. May be reasonable to administer with other management to improve sustained relief
  4. Agents with weaker evidence
    1. Intranasal Dihydroergotamine 0.5 mg bilateral nares
      1. Reduces Headache severity
      2. Does not decrease cluster frequency or duration
      3. Andersson (1986) Cephalalgia 6:51-4 [PubMed]
    2. Intranasal Capsaicin
      1. Applied to ipsilateral nostril bid for 7 days
      2. Marks (1993) Cephalalgia 13:114-6 [PubMed]
    3. Octreotide (Sandostatin)

XIII. Management: Prophylaxis for Episodic Cluster Headaches

  1. See Migraine Prophylaxis
  2. Verapamil
    1. First-line agent for prophylaxis (best evidence)
    2. Obtain baseline EKG
    3. Dosing
      1. Minimum effective dose is 240 mg (as a single dose or in divided doses)
      2. Start: 80 mg orally three times daily (or XR at 240 mg orally once daily)
      3. Titrate: Increase to 120 to 160 mg orally three times daily (or up to XR at 480 mg orally once daily)
  3. Corticosteroids
    1. Consider as Bridging Therapy from acute cluster Headache Management to prophylaxis
    2. Prednisone 50 mg for 1-3 days and then tapering over 10-14 days
  4. Suboccipital Corticosteroid Injection
  5. Other agents (variable efficacy)
    1. Indomethacin 25-50 mg three times daily
    2. Anticonvulsants
      1. Valproic Acid
      2. Topiramate (Topamax)
      3. Gabapentin (Neurontin)
  6. Avoid agents with serious adverse effects
    1. Methylsergide
      1. No longer recommended due to systemic fibrosis

XIV. Management: Prophylaxis for Chronic Cluster Headaches

  1. Verapamil
    1. See dosing above under prophylaxis of episodic Cluster Headache
  2. Lithium
    1. Dose: 300-600 mg/day initially (Maximum 900 mg/day)
    2. Base dose on serum Lithium levels
    3. Requires careful monitoring (Lithium level, TSH, Renal Function)
  3. Galcanezumab (Emgality)
    1. CGRP Antagonist FDA approved for Cluster Headaches
    2. Consider if refractory to other measures (very expensive)
  4. Refractory management
    1. Deep Brain Stimulation

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Related Studies

Ontology: Cluster Headache (C0009088)

Definition (MSH) A primary headache disorder that is characterized by severe, strictly unilateral PAIN which is orbital, supraorbital, temporal or in any combination of these sites, lasting 15-180 min. occurring 1 to 8 times a day. The attacks are associated with one or more of the following, all of which are ipsilateral: conjunctival injection, lacrimation, nasal congestion, rhinorrhea, facial SWEATING, eyelid EDEMA, and miosis. (International Classification of Headache Disorders, 2nd ed. Cephalalgia 2004: suppl 1)
Concepts Disease or Syndrome (T047)
MSH D003027
ICD9 339.02, 339.00
ICD10 G44.0 , G44.02, G44.00, G44.029, G44.009
SnomedCT 193032002, 155048007, 55865003, 193034001, 267699004, 193031009, 193947008, 230473009
LNC LA15138-3
English Headaches, Cluster, CLUSTER HEADACHES, CLUSTER HEADACHE, Cluster Headaches, HEADACHE HISTAMINE, HEADACHE VASOMOTOR, HORTON'S HEADACHE, Headache, Cluster, Hortons Syndrome, Cluster Headache, cluster headache (diagnosis), cluster headache, Cluster headache syndrome, unspecified, Cluster headaches, Headaches cluster, Headache histamine, Headache vasomotor, Cephalgia, Histamine, Histamine Cephalgia, Cephalgias, Histamine, Histamine Cephalgias, Chronic Cluster Headache, Chronic Cluster Headaches, Cluster Headache, Chronic, Cluster Headaches, Chronic, Headache, Chronic Cluster, Headaches, Chronic Cluster, Ciliary Neuralgia, Neuralgia, Ciliary, Ciliary Neuralgias, Neuralgias, Ciliary, Cluster Headache Syndrome, Cluster Headache Syndromes, Headache Syndrome, Cluster, Headache Syndromes, Cluster, Syndrome, Cluster Headache, Syndromes, Cluster Headache, Horton Syndrome, Horton's Syndrome, Syndrome, Horton, Syndrome, Horton's, Migraine, Neuralgic, Migraines, Neuralgic, Neuralgic Migraine, Neuralgic Migraines, Cluster headache syn NOS, Cluster headache NOS, Chronic cluster headache NOS, Cluster headache syndrome NOS, Cluster Headache [Disease/Finding], horton's neuralgia, headache cluster, headaches cluster, hortons syndrome, Headache;cluster, chronic cluster headaches, clusters headache, migrainous neuralgia, cluster headache syndrome, headaches histamine, histamine cephalgia, horton's headache, cluster headaches, horton syndrome, horton's syndrome, headache histamine, chronic cluster headache, chronic cluster headache (diagnosis), cluster headache chronic, Cluster headache (disorder), Histamine headache, Cluster headache, Ciliary neuralgia, Histamine cephalgia, Horton's headache, Horton's neuralgia, Migrainous neuralgia, Cluster headache syndrome, Neuralgic migraine, Chronic cluster headache, Vasomotor headache, Chronic cluster headache (disorder), Ciliary neuralgia (disorder), Cluster headache syndrome (disorder), histamine headache, Horton, ciliary; neuralgia, cluster; headache, headache; cluster, headache; histamine, histamine; headache, migrainous; neuralgia, neuralgia; ciliary, neuralgia; migrainous, syndrome; cluster headache, Cluster headache (disorder) [Ambiguous], cluster; headache syndrome
Portuguese CEFALEIA HISTAMINICA, Cefaleias cluster, Cefaleia histamínica, Cefaleia vasomotora, Nevralgia tipo enxaqueca, CEFALEIA DE HORTON, CEFALEIA VASOMOTORA, CEFALEIAS EM SALVA, Cefaleia Histamínica, Cefaleia em Cacho, Cefalalgia Histamínica, Cefaleia de Horton, Cefalgia Histamínica, Enxaqueca Nevrálgica, Nevralgia Ciliar, Síndrome de Horton
Dutch hoofdpijn histamine, hoofdpijn cluster, migraineuze neuralgie, Hortonse hoofdpijn, hoofdpijn vasomotorisch, ciliair; neuralgie, cluster; hoofdpijn, histamine; hoofdpijn, hoofdpijn; cluster, hoofdpijn; histamine, migraine-achtig; neuralgie, neuralgie; ciliair, neuralgie; migraine-achtig, syndroom; clusterhoofdpijn, Cluster-hoofdpijnsyndroom, cluster hoofdpijn, cluster; hoofdpijnsyndroom, Ciliaire neuralgie, Clusterhoofdpijn, Histamine-cefalgie, Hoofdpijn, cluster-, Horton, neuralgie van, Neuralgie van Horton, Neuralgische migraine
French Neuralgie migraineuse, Algies vasculaires de la face, Céphalée vasomotrice, Céphalée de Horton, ALGIES VASCULAIRES DE LA FACE, CEPHALEE HISTAMINIQUE, CEPHALEE VASOMOTRICE, CEPHALEES DE HORTON, Céphalée vasculaire de Horton, Algie vasculaire de la face, Céphalée histaminique, AVF (Algie Vasculaire de la Face), Syndrome de Bing-Horton
German Cluster-Kopfschmerzen, vasomotorischer Kopfschmerz, Clusterkopfschmerzen, Histaminkopfschmerz, Horton-Kopfschmerzen, migraeneartige Neuralgie, CLUSTERKOPFSCHMERZEN, HISTAMINKOPFSCHMERZ, HORTONSCHER KOPFSCHMERZ, KOPFSCHMERZEN VASOMOTORISCH, Cluster-Kopfschmerz, Histamin-Kopfschmerz, Histaminbedingte Zephalgie, Horton-Syndrom, Kopfschmerz, Cluster-, Neuralgische Migraine, Ziliarneuralgie
Italian Cefalea da istamina, Nevralgia emicranica, Cefalee a grappolo, Cefalea vasomotoria, Cefalgia istaminica, Cefalea a grappolo cronica, Cefalea di Horton, Emicrania nevralgica, Neuralgia ciliare, Cefalea a grappolo
Spanish Cefalea vasomotora, Cefalea por histamina, Cefalea en brotes, Cefalea en acúmulos, Neuralgia migrañosa, Cefalea de Horton, cefalea crónica salvas, CEFALEA DE HORTON, CEFALEA HISTAMINICA, CEFALEA VASOMOTORA, cefalea vasomotora, cefalea acuminada (trastorno), cefalalgia histamínica, neuralgia con migraña, cefalea de Horton, cefalea acuminada (concepto no activo), cefalea acuminada, cefalea crónica salvas (trastorno), cefalea de Horton crónica, cefalea en acúmulos, cefalea en grupos, cefalea en racimos crónica, cefalea en racimos, cefalea en salvas (trastorno), cefalea en salvas crónica (trastorno), cefalea en salvas crónica, cefalea en salvas, cefalea en tandas crónica, cefalea en tandas, cefalea histaminérgica crónica, cefalea histaminérgica, cefalea histamínica crónica, cefalea histamínica, migraña neurálgica crónica, migraña neurálgica, neuralgia ciliar (trastorno), neuralgia ciliar, neuralgia de Horton, Cefalea en racimos, Cefalalgia en Racimos, Cefalalgia Histamínica, Cefalea Histamínica, Neuralgia Ciliar, Neuralgia Migrañosa, Síndrome de Horton
Swedish Klusterhuvudvärk
Japanese グンパツズツウ, ホートンズツウ, ケッカンウンドウセイズツウ, ヘンズツウセイシンケイツウ, グンハツズツウ, ヒスタミンセイズツウ, クラスター頭痛, 頭痛-群発, ヒスタミン性頭痛, ホートン症候群, ホートン頭痛, 片頭痛性神経痛, 群発頭痛, 自律神経性頭痛, 血管運動性頭痛, 錐体神経痛, ホルトン症候群, 群発性頭痛, 頭痛-自律神経性
Finnish Sarjoittainen päänsärky
Czech Cluster headache, Hortonova bolest hlavy, Histaminová bolest hlavy, Vazomotorická bolest hlavy, Migrenózní neuralgie, Hortonův syndrom, ciliární neuralgie, migréna sdružená, cluster headache, Bingova-Hortonova cefalea, klastrová bolest hlavy, Bingova-Hortonova bolest hlavy
Korean 송이두통 증후군
Polish Hemikrania naczynioporaźna, Neuralgia nerwu skalistego, Ból głowy klasterowy, Neuralgia nerwu rzęskowego, Ból głowy Hortona
Hungarian Cluster fejfájások, Horton-fejfájás, Migraines neuralgia, Histamin fejfájás, Vasomotoros fejfájás, Cluster fejfájás
Norwegian Hortons hodepine, Klasehodepine, Clusterhodepine

Ontology: Trigeminal Autonomic Cephalalgias (C1565172)

Definition (MSH) Primary headache disorders that show symptoms caused by the activation of the AUTONOMIC NERVOUS SYSTEM of the TRIGEMINAL NERVE. These autonomic features include redness and tearing of the EYE, nasal congestion or discharge, facial SWEATING and other symptoms. Most subgroups show unilateral cranial PAIN.
Concepts Disease or Syndrome (T047)
MSH D051303
SnomedCT 449814007
Czech nervus trigeminus - autonomní cefalalgie, trigeminální autonomní cefalalgie, nerv trojklaný - autonomní cefalalgie
Finnish Kolmoishermon autonomiset päänsäryt
Swedish Trigeminal autonom cefalalgi
English trigeminal autonomic cephalgia (diagnosis), trigeminal autonomic cephalgia, Trigeminal Autonomic Cephalalgias [Disease/Finding], Trigeminal autonomic cephalalgia (disorder), Trigeminal autonomic cephalgia, Trigeminal autonomic cephalalgia, Cephalalgia, Trigeminal Autonomic, Cephalalgias, Trigeminal Autonomic, Trigeminal Autonomic Cephalalgias, Trigeminal Autonomic Cephalalgia
Polish Bóle głowy związane z układem autonomicznym nerwu trójdzielnego, Bóle głowy trójdzielno-autonomiczne
Spanish cefalalgia autonómica del trigémino, cefalalgia autonómica del trigémino (trastorno), Cefalea Autónoma del Trigémino, Cefalea Autónoma Trigeminal, Cefalalgia Autónoma del Trigémino
Norwegian Autonom trigeminushodepine, Autonom trigeminusnevralgi
Portuguese Cefalalgias Autonômicas do Trigêmeo, Cefaleias Trigêmino-Autonômicas, Cefaleias Autonômicas do Trigêmeo, Cefalalgias Autonômicas Trigeminais, Cefalalgias Trigêmino-Autonômicas, Cefalgias Autonômicas do Trigêmeo, Cefalgias Trigêmino-Autonômicas
German Trigeminoautonome Kopfschmerzen
Italian Cefalalgie autonome del trigemino, Cefalee autonome del trigemino
French Céphalalgies autonomes du trijumeau, Céphalées trigémino-autonomiques