Headache, Cluster

Basics

Description

  • A primary headache disorder characterized by circadian and circannual episodes consisting of multiple attacks of severe, unilateral sharp, searing, or piercing pain typically localized to the periorbital and/or temporal areas
  • It is the most common headache among trigeminal autonomic cephalgias (TACs)
  • Accompanied by signs of ipsilateral parasympathetic autonomic activation as well as restlessness or agitation
  • Autonomic symptoms: signs of parasympathetic hyperactivity (ipsilateral lacrimation, eye redness, nasal congestion) and sympathetic hypoactivity (ipsilateral ptosis and miosis)
  • Individual attacks occur from once every other day up to 8 times per day and can last 15 to 180 min/day if untreated.
  • Attacks usually occur in series (cluster periods) that are often seasonal, lasting for weeks or months, and are separated by remission periods usually lasting months to years.
  • About 10–15% of patients have chronic symptoms without remission periods (i.e., chronic cluster headache [cCH]).

Epidemiology

Prevalence

1-year prevalence: 53/100,000

  • Gender: male > female; 4.3:1 overall
  • Mean age of onset: 30 years; women often develop cluster headache (CH) earlier in life (20s).

Etiology and Pathophysiology

Complex and incompletely understood; possible mechanisms include the following:

  • Activation of the trigeminovascular and parasympathetic system which leads to the release of neurokinins and vasodilatory peptides including vasoactive intestinal peptide (VIP), and calcitonin gene-related peptide (CGRP)
  • Posterior hypothalamus activation; hypothalamic-midbrain-brainstem interconnections may trigger an attack by activating trigeminal nociceptive pathways through increased parasympathetic outflow.
  • Alterations in the descending pain modulation network and disordered pain modulation during cluster periods
  • Dysregulation of areas of the brain related to circadian rhythm and chronobiology, including the pineal gland, suprachiasmatic nucleus, and other “clock” areas

Genetics

  • Autosomal dominant in 5% of cases; otherwise, recessive or multifactorial
  • First-degree relatives are 5 to 18 times more likely, and second-degree relatives are 1 to 3 times more likely to be affected by cluster headaches.
  • >50% with migraine and 18% with CH in family history
  • Association of core circadian genes and other clock-controlled genes (CCGs), which have a circadian pattern of expression

Risk Factors

  • Age: 70% onset before age 30 years
  • Cigarette smoking or childhood exposure to cigarette smoke
  • History of head trauma

Commonly Associated Conditions

  • Depression (24%) with increased risk of suicide
  • History of migraine, frequently in female patients; medication-overuse headache
  • Asthma (9%)
  • Sleep apnea (30–80%)

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