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
• 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)
• Patients often pace the floor during an acute attack because lying down seems to exacerbate the pain.
• Individual attacks occur from once every other day up to 8 times per day and can last 15 to 180 minutes per 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 remissions (i.e., chronic cluster headache [cCH]).

Epidemiology

Prevalence
Prevalence: 53/100,000

• Gender: male > female; 4.3:1 overall
• Mean age of onset: 30 years; women often develop CH earlier in life (20s).
• Episodic/chronic ratio: 6:1

Etiology and Pathophysiology

Complex and incompletely understood, possible mechanisms include the following:

• Activation of the trigeminovascular system, which leads to the release of vasodilatory peptides including substance P, neurokinin, and calcitonin gene-related peptide (CGRP)
• Posterior hypothalamus activation and the hypothalamic-brainstem-cerebellar 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

Genetics

• Autosomal dominant in 5% of cases; otherwise, recessive or multifactorial
• First-degree relatives are 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

Risk Factors

• Male gender
• 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%)