Cluster Headache

See Also

Epidemiology

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: 124 per 100,000 (~1 in 1000)
  2. One year: 53 per 100,000
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
Age of onset
1. Rare in children under age 10 years old
2. Male: 20 to 40 years old
3. Female: Onset peaks in 60s (especially in black women)
Hereditary
1. Autosomal Dominant inheritance pattern in 5% of Cluster Headache patients
2. First degree relative with Cluster Headache confers 5 to 18 fold increase in Cluster Headache risk
3. Associated with the HCRTR2 gene

Pathophysiology

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

Types
Trigeminal Autonomic Cephalalgia

Cluster Headache (most common)
1. Severe unilateral Headaches (orbital, supraorbital or temporal) lasting up to 3 hours, as often as 8 times daily
  1. See Diagnosis below
2. Episodic (90%)
  1. At least 2 cluster periods each lasting one week or more (but less than one year)
  2. Remission periods last >3 months
3. Chronic (10%)
  1. Headaches occur for more than one year
  2. Remissions last <3 months
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

Risk Factors

Tobacco Abuse
Family History of Headache (esp. first degree relative with Cluster Headache)
Head Injury
Shift work
See triggers below

Symptoms
Cluster Headache

Characteristics
1. Deep pain
2. Burning, stabbing, or lancinating type pain
Severity
1. Excruciating pain
2. Patient may even consider Suicide (hence the common name, "Suicide Headache")
Location
1. Unilateral Headache typically behind one eye
2. May be orbital, supraorbital or temporal pain
3. Radiates to upper teeth, jaw or neck
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
Triggers
1. Sleep Apnea
2. Food containing nitrates
3. Nail varnisn
4. Petroleum
5. Vasodilators
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)

Evaluation

See Headache Evaluation

Imaging

Routine head imaging is no longer recommended
1. Previously MRI Brain with and without contrast was recommended in all Trigeminal Autonomic Cephalalgia
Indications for head imaging (Head CT or Brain MRI)
1. See Headache Red Flags
2. Sudden changes in Headache features
3. Signs of infection
4. Focal neurologic findings (e.g. weakness, Double Vision or Vision Loss, mental status changes)

Diagnosis
Cluster Headache

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 and or Ptosis
  6. Restlessness or Agitation
Timing
1. Episodic Cluster Headache
  1. Two or more cluster periods lasting 7-365 days and separated by pain-free remissions >3 months
2. Chronic Cluster Headache
  1. Episodes recur for more than 1 year without remission or with remission <3 months
References
1. (2018) Cephalgia 38(1):1-211 [PubMed]

Differential Diagnosis

Migraine Headache
1. Common Migraine features do not distinguish from Cluster Headache
  1. Aura occurs in 14% of Cluster Headaches
  2. Photophobia occurs in >50% of Cluster Headaches
2. Migraine Headaches are worsened with movement
  1. Contrast with Cluster Headaches in which patients are restless and agitated
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
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
Brief Neuralgiform Headache with cranial autonomic symptoms
Orbital Myositis
1. Similar to Cluster Headache with longer duration
Tension Headache
Trigeminal Neuralgia
1. Typically affects second and third branches of the Trigeminal Nerve (V2, V3)
2. In contrast when the first branch (V1) is affected, findings are consistent with Cluster Headache
Intracranial Mass (e.g. Pituitary Adenoma)

Management
Nonpharmacologic measures

Relaxation Techniques
Cognitive-behavior therapy
Treat comorbid Mood Disorders
Tobacco Cessation
Alcohol cessation

Management
Abortive Treatment for Acute Cluster Headache

See Migraine Treatment
First line agents
1. 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
    1. Cohen (2009) JAMA 302(22): 2451-7 [PubMed]
  3. Home use is often covered by private insurance but not by Medicare and medicaid
2. Triptan Agents
  1. See Triptans for adverse effects and contraindications
  2. Sumatriptan (Imitrex)
    1. Intranasal 20 mg (may repeat once in 24 hours)
      1. Slower onset than subcutaneous Sumatriptan
    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
  3. Zolmitriptan
    1. 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. Oral: 5 mg orally (may repeat once in 24 hours)
      1. Second line option limited to acute episodic Cluster Headache
Agents with weaker evidence
1. Intranasal Lidocaine 4-10% solution
  1. Dose: 1 ml intranasally
    1. Lidocaine 10% applied 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 three times daily 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
3. Octreotide (Sandostatin)
  1. 100 mcg/ml SC decreases Headache severity
  2. Matharu (2004) Ann Neurol 56(4): 488-94 [PubMed]
4. 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]
5. Intranasal Capsaicin
  1. Applied to ipsilateral nostril bid for 7 days
  2. Marks (1993) Cephalalgia 13:114-6 [PubMed]

Management
Transitional from Abortive to Prophylaxis

Suboccipital Corticosteroid Injection
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

Management
Prophylaxis for Cluster Headaches

See Migraine Prophylaxis
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)
Second-line agents when Verapamil is ineffective or contraindicated
1. Melatonin 10 mg orally daily
2. Nasal Civamide 50 mcg (not available in U.S.)
3. 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)
4. Galcanezumab (Emgality)
  1. CGRP Antagonist FDA approved for Cluster Headaches
  2. Consider if refractory to other measures (very expensive)
  3. In study was administered monthly for 3 months
    1. Goadsby (2019) N Engl J Med 381(2): 132-41 [PubMed]
Refractory management
1. Sphenopalatine Ganglion stimulation
  1. Shoenen (2013) Cephalgia 33(10): 816-30 [PubMed]
2. Gamma Knife Radiotherapy
  1. Kano (2011) J Neurosurg 114(6): 1736-43 [PubMed]
3. Noninvasive Vagal Nerve Stimulation (FDA approved)
Other agents (variable efficacy)
1. Indomethacin 25-50 mg three times daily
2. Anticonvulsants
  1. Topiramate (Topamax)
  2. Gabapentin (Neurontin)
Avoid agents not recommended due to lack of efficacy or with serious adverse effects
1. Valproic Acid
  1. Does not appear effective in Cluster Headaches
2. Methylsergide
  1. No longer recommended due to systemic fibrosis

References