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BASICS

Description

  • Primary headache disorder with multiple severe, unilateral attacks localized to periorbital/temporal area.
  • Most common trigeminal autonomic cephalalgia (TAC).
  • Attacks accompanied by ipsilateral parasympathetic activation (lacrimation, conjunctival injection, nasal congestion) and sympathetic hypoactivity (ptosis, miosis).
  • Frequency: 1 attack every other day up to 8 per day, lasting 15–180 minutes untreated.
  • Cluster periods last weeks to months; remission typically months to years.
  • Chronic cluster headache (cCH) in 10-15% without remission.

Epidemiology

  • Prevalence: 53 per 100,000 annually.
  • Male predominance 4.3:1.
  • Mean onset ~30 years; women present earlier.
  • Episodic:chronic ratio ~6:1.

Etiology and Pathophysiology

  • Trigeminovascular activation releasing vasodilators: substance P, neurokinin, CGRP.
  • Posterior hypothalamus involvement triggers trigeminal nociceptive pathways via parasympathetic outflow.
  • Altered descending pain modulation.
  • Genetics: autosomal dominant in 5%, multifactorial otherwise.
  • Family history increases risk significantly.

Risk Factors

  • Age <30 (70% onset)
  • Smoking (active or passive exposure)
  • History of head trauma

Associated Conditions

  • Depression (24%), increased suicide risk.
  • Migraine history (common in females).
  • Asthma (9%)
  • Sleep apnea (30–80%)

DIAGNOSIS

Diagnostic Criteria (ICHD-3, 2018)

  • ≥5 attacks of unilateral orbital, supraorbital, and/or temporal pain lasting 15–180 min.
  • ≥1 ipsilateral autonomic symptom (lacrimation, conjunctival injection, nasal congestion, rhinorrhea, eyelid edema, forehead/facial sweating, miosis, ptosis).
  • Restlessness or agitation during attacks.
  • Frequency: 1 every other day to 8 per day during cluster period.
  • Episodic: ≥2 cluster periods lasting 7 days to 1 year, separated by ≥3 months pain-free.
  • Chronic: attacks ≥1 year without remission or remission <3 months.

History

  • Excruciating unilateral sharp, searing pain periorbital/temporal.
  • Ipsilateral autonomic symptoms.
  • Circadian pattern: attacks often at same time daily, often nocturnal.
  • Pacing or restlessness during attack.
  • Triggers: alcohol, nitroglycerin, sildenafil, histamine, strong odors.
  • Seasonal recurrence.

Physical Exam

  • Usually normal outside attacks.
  • During attacks: agitation, distress, ipsilateral conjunctival injection, lacrimation, eyelid edema, ptosis, miosis, nasal congestion, rhinorrhea.

Differential Diagnosis

  • Other TACs: paroxysmal hemicrania, SUNCT, hemicrania continua.
  • Hypnic headache, trigeminal neuralgia.
  • Migraine.
  • Temporal arteritis.
  • Herpes zoster.
  • Acute angle closure glaucoma.
  • Secondary cluster headache (vascular lesions, tumors, infections, inflammation).

DIAGNOSTIC TESTS

Tests

  • Diagnosis clinical; often delayed (median 5 years).
  • MRI/CT brain including pituitary and cavernous sinus to exclude mimics.

TREATMENT

General Measures

  • Avoid sleep habit changes.
  • Stop smoking.
  • Avoid alcohol and chemical triggers during cluster period.

Medications

Abortive (Acute)

  • Oxygen 100% at 12–15 L/min via nonrebreather mask; relief within 15 min.
  • Sumatriptan SubQ 6 mg (up to 12 mg/24 h); intranasal 20 mg (max 40 mg/24 h).
  • Zolmitriptan intranasal and oral formulations.
  • Noninvasive vagus nerve stimulation (FDA approved).

Cautions

  • Triptans contraindicated in ischemic cardiac disease, uncontrolled hypertension, stroke, peripheral vascular disease.

Second-line abortive

  • Intranasal lidocaine.
  • SubQ octreotide.

Transitional Therapy

  • Occipital nerve steroid injections (cortivazol 3.75 mg).
  • Oral prednisone taper (60–100 mg/day, taper ≤18 days).

Preventive Therapy

  • Verapamil: start 80 mg TID, titrate up to 480–960 mg/day.
  • Galcanezumab (monoclonal antibody against CGRP) monthly during cluster.
  • Lithium (600–1500 mg/day).
  • Topiramate, gabapentin (adjunctive).
  • Noninvasive vagus nerve stimulation.

Pregnancy Considerations

  • Oxygen first-line.
  • Use triptans and steroids with caution.
  • Avoid ergotamines.

Surgery and Other Procedures

  • Limited evidence for hyperbaric oxygen, CPAP, Botox.
  • Surgery or gamma knife for refractory cases.
  • Neuromodulation experimental and for refractory patients.

ONGOING CARE

Monitoring

  • Anticipate clusters; start prophylaxis early.
  • Monitor depression and suicide risk.

Lifestyle

  • Avoid alcohol.

Prognosis

  • Often chronic or unpredictable.
  • Attack frequency may decrease with age.
  • Possible progression from episodic to chronic.

Complications

  • Depression and suicide risk.

Clinical Pearls

  • Patients often agitated during attacks.
  • High-flow oxygen and triptans preferred over narcotics.
  • Injected triptans most effective.
  • Comprehensive treatment includes abortive, transitional, and prophylactic therapies.

References

  1. Diener HC, May A. Drug treatment of cluster headache. Drugs. 2022;82(1):33-42.
  2. Robbins MS, Starling AJ, Pringsheim TM, et al. Treatment of cluster headache: the American Headache Society evidence-based guidelines. Headache. 2016;56(7):1093-1106.
  3. Gordon A, Roe T, Villar-Martínez MD, et al. Effectiveness and safety profile of greater occipital nerve blockade in cluster headache: a systematic review. J Neurol Neurosurg Psychiatry. 2023;jnnp-2023-331066.
  4. Yuan H, Spare NM, Silberstein SD. Targeting CGRP for the prevention of migraine and cluster headache: a narrative review. Headache. 2019;59(Suppl 2):20-32.
  5. Bjørk MH, Kristoffersen ES, Tronvik E, et al. Management of cluster headache and other trigeminal autonomic cephalalgias in pregnancy and breastfeeding. Eur J Neurol. 2021;28(7):2443-2455.