Cluster headaches (CH) are a rare form of severe disabling headache. CH is characterized by episodes of severe unilateral pain in the orbital, supraorbital and/or temporal areas that last from 15 to 180 minutes, with recurrence up to 8 times daily. It is accompanied by local signs and symptoms of autonomic dysfunction occurring on the side, such as conjunctival redness, tearing eyes, nasal congestion, rhinorrhea, sweating of the face and forehead, myosis, ptosis, and edema of the eyelid. The attacks occur in series lasting weeks or months. The attacks are extremely painful, so that CH is also commonly called suicide headache. There are two forms of CH: episodic CH, characterized by alternating active periods, with daily or almost daily attacks lasting from 7 days to one year, and remission periods lasting one month or more that are totally symptom free; and chronic CH, in which attacks recur for greater than one year without remission or with remissions lasting less than one month. CH mainly affects young adults, predominantly males (M/F sex ratio = 4) and available evidence suggests that it is a lifelong disorder in the majority of patients, but with longer remission periods over time.
Although, the exact pathogenesis of this condition remains unclear, the underlying abnormality is in the posterior hypothalamus with subsequent trigeminovascular and cranial autonomic activation. Alcohol, nicotine, exercise, and elevated environmental temperature are recognized as triggers of CH. The treatment of CH is only symptomatic. The only two treatments of attacks with proven efficacy are subcutaneous sumatriptan and oxygen inhalation.
CH has traditionally been considered a sporadic disease. Recently, however, a familial recurrence has been appreciated as several CH cases have been observed in family pedigrees. Furthermore, family studies indicate that first-degree relatives of CH probands carry a 5- to 18-fold and the second degree relatives carry a 1- to 3-fold increased relative risk of the disease. CH has been considered a probable autosomal dominant disease with a penetrance of 0.3-0.34 in males and 0.17-0.21 in females. However, autosomal recessive pattern has been suggested in certain families. In addition, the hypocretin receptor 2 (HCRTR2) G1246A polymorphism has been associated with the risk for cluster headache.