Five hundred and fifty-four patients with episodic cluster headache (ECH) and chronic cluster headache (CCH) were examined between 1963 and 1997. Mean age at onset was significantly higher in women with CCH compared with women with ECH and in men with ECH or CCH. In women with CCH age at onset was evenly distributed from 10 to 69 years, whereas in men with CCH and in both sexes with ECH, there was a peak when they were in their 20s. In women with ECH a second peak of onset occurred in their 50s. Although not statistically significant, primary CCH started later in women (mean 50.8 years) than secondary CCH (mean 35.5 years). There was a significant variation in the male : female ratio with respect to age at onset, being largest between 30 and 49 years of age (ECH 7.2 : 1; CCH 11.0 : 1) and lowest after 50 (ECH 2.3 : 1; CCH 0.6 : 1). During the observation period of more than 30 years there was a trend towards a decreasing male preponderance; the male : female ratio was significantly higher among patients with onset before rather than after 1970. The proportion of episodic vs. chronic CH did not change during the study period. The nature of the sex- and age-related pattern of cluster headache onset remains to be elucidated but mechanisms associated with sex hormone regulation, perhaps of hypothalamic origin, may be involved, as well as environmental factors related to lifestyle.

The major objective of the present study was to estimate genetic and environmental influences on recurrent headaches in prepubescent twins. A nationwide cohort of 8 to 9-year-old Swedish twins (n = 1,480) was screened for nonsymptomatic and recurrent headaches through a questionnaire mailed to their parents (75% response frequency). Among positives, 79% of headaches were classified as migraine or tension-type headache in close accordance with the International Headache Society criteria. The prevalences of migraine and nonmigrainous headaches were 2.4% and 11.3%, respectively, and without significant differences between the sexes or zygosity types. Inheritance on liability to recurrent headaches was estimated to 70% (a2 = 0.70, 95% CI = 0.54-0.82) for boys and girls but the genetic effect was found to be uncorrelated between the sexes. We conclude that genetic and individual specific effects are important for recurrent headaches of migrainous and nonmigrainous types in prepubescent children, and that different genetic etiologies might exist for boys and girls.

Glyceryl trinitrate (GTN) is known to induce single extra attacks of cluster headache (CH) during active cluster periods, most probably via actions of nitric oxide (NO). Induction of whole periods of CH by organic nitrates has, however, attracted little attention in the literature. We report on eight patients with episodic CH and coexistent effort-induced angina pectoris. Cases 1-6 had been free of their headaches for many years but got recurrence of CH within a few weeks after the administration of long-acting organic nitrates (isosorbide-dinitrate, isosorbide-5-mononitrate or slow-release GTN) aimed at treating their chest pains. These nitrate-induced headache periods were more severe and had a longer duration than the previous spontaneous ones. Furthermore, one of the subjects and two additional cases experienced a marked reduction of their anginal attacks during successive CH periods. Exercise time to effort-induced angina was increased in all three patients and one of them revealed a markedly elevated threshold for eliciting ischaemic cardiac symptoms by standardized physical exercise on a cycle ergometer. We hypothesize whether extra CH periods elicited by sustained nitrate therapy and remission of angina pectoris during active clusters are caused by central mechanisms involving inhibition of sympathetic tone and effects on both cranial vessels and cardiac functions.

Twin Res. 2002;5:277‐286. To explore age‐related mechanisms in the expression of recurrent headache, we evaluated whether genetic and environmental influences are a function of the reporting age using questionnaire information that was gathered in 1973 for 15‐ to 47‐year‐old Swedish twins (n  =  12,606 twin pairs). Liability to mixed headache (mild migraine and tension‐type headache) was explained by non‐additive genetic influences (49%) in men aged from 15 to 30 years and additive genetic plus shared environmental influences (28%) in men aged from 31 to 47 years. In women, the explained proportion of variance, which was mainly due to additive genetic effects, ranged from 61% in adolescent twins to 12% in twins aged from 41 to 47 years, whereas individual specific environmental variance was significantly lower in twins aged from 15 to 20 years than in twins aged from 21 to 30 years. Liability to migrainous headache (more severe migraine) was explained by non‐additive genetic influences in men, 32% in young men and 45% in old men, while total phenotypic variance was significantly lower in young men than in old men. In women, the explained proportion of variance ranged from 91% in the youngest age group to 37% in the oldest age group, with major contributions from non‐additive effects in young and old women (15‐20 years and 41‐47 years, respectively) and additive genetic effects in intermediate age groups (21‐40 years). While total variance showed a positive age trend, genetic variance tended to be stable across age groups, whereas individual specific environmental variance was significantly lower in adolescent women as compared to older women. Comment: Does this mean that most of the genetic contribution to headache in women is likely to occur during adolescence, which would be in agreement with the peak incidence? Some clinical interpretation would be helpful here. DSM