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A double-blind trial of dihydroergotamine (DHE) nasal spray compared with placebo was carried out in patients with cluster headache. Twenty-five patients were included in the trial. In three patients, all receiving DHE, the pain attacks ceased after five attacks. In the other 22 patients, 133 attacks were treated with placebo and 137 attacks with DHE nasal spray (dosage, 1 mg of DHE). The trial showed that the treatment given has no effect on the attack frequency or the duration of the single attack. However, the treatment had a significant effect on the intensity of the single attacks. It can be concluded that the trial should be repeated, using a larger dosage of DHE. This should be ethically justifiable, since none of the patients had any adverse reactions locally in the mucous membrane of the nose or systemically.

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We investigated the familial occurrence of cluster headache in 370 probands with cluster headache, diagnosed according to the operational diagnostic criteria of the international Headache Society. Seven probands belonged to three families. A positive family history of cluster headache was found in 7% (25 of 366) of the families. Compared with the general population, the first- and second-degree relatives of the 370 probands with cluster headache had a 14- and 2-fold increased risk of having cluster headache, after standardization for sex and age. This increased familial risk strongly suggests that cluster headache has a genetic cause. The patterns of segregation were assessed by complex segregation analysis performed with the computer program, POINTER. The segregation analysis suggests that cluster headache has an autosomal dominant gene with a penetrance of 0.30 to 0.34 in males and 0.17 to 0.21 in females. The gene is present in 3% to 4% of males and 7% to 10% of females with cluster headache.

Eighty-one patients were diagnosed as having migraine, tension headache or both according to previously used criteria. Then we performed a standardized interview to determine the frequency and severity of headache characteristics used in the new operational diagnostic criteria of the International Headache Society (IHS). In every patient the original diagnosis fulfilled also the IHS criteria, but in 9 patients the criteria were only fulfilled in half or less of the attacks, and applying the IHS criteria they also achieved an additional diagnosis. In one patient these attacks did not fulfill the pain criteria and in 8 (4 migraine, 4 tension headache) they did not fulfill the criteria for accompanying symptoms. Overall the IHS criteria are sensitive and specific, but they may possibly be improved with regard to accompanying symptoms. The present study suggests that recording of frequency and graded severity of characteristics using a headache diary may further improve the distinction between the different types of headache.

Our recent description of a 17- and 2-fold increased risk of cluster headache among first- and second-degree relatives, respectively, strongly suggests that cluster headache has a genetic cause. Eighteen families with familial occurrence of cluster headache according to the criteria of the International Headache Society were included. Clinical intra- and interfamilial variability of cluster headaches was analyzed in 44 cases (31 males and 13 females) from 18 families. None of the families showed a distinctive pattern of symptoms except for the two families with chronic cluster headache. Their affected male relatives had a high number (1-8) of attacks per day in their cluster periods. Children had a significantly lower age at onset than parents (p = 0.018), but it is uncertain whether this is a real phenomenon or caused by memory bias. However, the possible existence of anticipation is important in the search for the gene. Co-occurrence of migraine with and without aura was not increased in familial cases of cluster headache compared with the prevalence of migraine with and without aura in the Danish population, implying different etiologies. Our results suggest that episodic, chronic and chronic cluster headaches evolved from episodic have a common etiology and genetic heterogeneity is unlikely on clinical grounds.

One hundred and twenty seven patients with cluster headache have been compared with 122 patients with migraine. Twenty of the patients with cluster headache have had migraine attacks but only 2 still have migraine attacks after the onset of cluster headache. No migraine patients had cluster headache. Among the 127 patients with cluster headache, one of the parents suffered from cluster headache in 4.7% of the cases. Among the 122 patients with migraine, 0.8% had a parent with cluster headache. Among the 122 patients with migraine 54.9% had parents with migraine, and in the cluster headache group 23.6% of the patients had one parent with migraine. The coexistence of migraine and cluster headache is rare. The two types of headache, as far as the heredity pattern is concerned, are independent entities.