Histamine, 0.16, 0.33 and 0.66 microgram/kg/min, was infused intravenously to 13 normal non-headache-prone volunteers, 10 patients with chronic muscle contraction headache and 25 patients with common migraine. In the normal group no patients developed pulsating headache. In the migraine group 13 patients developed severe, 9 patients moderate and 2 patients mild pulsating headache, and only 1 patient failed to develop headache at all. The muscle contraction headache patients responded intermediately. At each infusion rate the headache was of constant quality and severity as long as the infusion continued, but disappeared shortly after its termination. Injection of an H1 blocking agent, mepyramine, almost immediately abolished the headache. The H2 blocker cimetidine was much less effective, but still significantly better than placebo. The i.v. histamine infusion test is a useful model for the study of experimental vascular headache.

In the first three months of a 24-month open study to assess the safety and efficacy of subcutaneous sumatriptan 6 mg in the long-term acute treatment of cluster headache, 138 patients treated a maximum of two attacks daily each with a single 6 mg injection. A total of 6353 attacks were treated. Adverse events, reported in 28% of sumatriptan-treated attacks, were qualitatively similar to those seen in migraine long-term trials. Their incidence did not increase with frequent use of sumatriptan. There were no clinically significant treatment effects on vital signs, ECG recordings or laboratory parameters. Headache relief (a reduction from very severe, severe or moderate pain to mild or no pain) at 15 min was obtained for a median of 96% of attacks treated. There was no indication of tachyphylaxis, decrease in the speed of response, or increased frequency of attacks with long-term treatment. This study demonstrated that, in long-term use, subcutaneous sumatriptan 6 mg is a well-tolerated and effective acute treatment for cluster headache.

The purpose of this paper is to analyse methodological aspects of prophylactic drug trials in migraine. A study of ferrum quartz in 33 patients provided the necessary data base. Migraine definitions, relation between interval headache and migraine, and a number of other clinical problems are discussed. A headache diary is presented which to a certain extent allows a separation of internal headache and migraine attacks. Virtually all patients with frequent migraine attacks have interval headaches. A statistical model which allows a separation of time effects and treatment effects is presented. The inter-patient variability was much greater than intra-patient variability. This indicates that it will be difficult to obtain sufficient power with a non-crossover design. The relation between duration of treatment periods and the necessary number of patients is shown to be inversely related.

This multinational, multicenter, randomized, double-blind, placebo-controlled study in 169 patients investigated the effect of a 7-day period of preemptive treatment with oral sumatriptan (100 mg tid) on the frequency and severity of cluster headache attacks occurring during an established cluster headache period. Safety and tolerability were also assessed. Cluster headache patients who were not taking prophylactic medication and had experienced seven or more attacks in the preceding observation week, treated a cluster headache attack at home with subcutaneous sumatriptan 6 mg using an autoinjector device. Patients were then randomized to take sumatriptan 100 mg or placebo at 8-hourly intervals for a 7-day period. Cluster headaches occurring during this period could be treated 5 minutes after onset with rescue medication (100% oxygen or simple analgesics). Diary cards were used to record details of the cluster headache pattern during the observation and study treatment weeks. Preemptive oral treatment with sumatriptan 100 mg tid for 7 days did not produce a significant reduction in the number or severity of cluster headache attacks occurring during an established cluster headache period. Oral treatment with sumatriptan 100 mg tid over a 7-day period was not associated with an increased or altered adverse event profile from that previously reported.

A follow-up study of 40 patients (migraine 39, cluster headache 1) previously treated for ergotamine abuse was conducted. Their statements regarding ergotamine intake were checked using butalbital (contained in the suppositories abused by 90% of the patients) as a tracer, and later by contact with the family doctor. Eleven patients abused ergotamine again during a median observation time of 21 months. Nineteen patients had more than a 50% reduction in headache days after withdrawal and half of the patients were relieved of other symptoms of ergotamine toxicity. Even with a failure rate of approximately 25% it is concluded that efforts to withdraw after abuse of ergotamine are worthwhile.

After 31 years of suffering from headache attacks which in the last five years were indistinguishable from migrainous neuralgia (cluster headache), a 52‐year‐old man was treated for an invasive adenoma of the pituitary gland. During a two‐year follow‐up period he has not had one single attack of his usual headache. The case history may suggest a causal relationship between the adenoma and the headache attacks.

A rapidly rotating single-photon emission tomograph was used to study regional cerebral blood flow (rCBF) by 133-Xenon inhalation in 18 patients with cluster headache. Measurements were performed in all patients in the resting state. The patients were given alcohol and/or nitroglycerin to provoke an attack of cluster headache. In eight patients it was possible to obtain satisfactory measurements during their cluster headache attack. All patients had a normal resting CBF with a normal age regression. During the headache phase, no significant changes of mean CBF from baseline occurred. There were no focal changes in the individual patient, but the mean rCBF in all eight patients showed significantly increased rCBF in the central, basal region and a small part of the right parietotemporal region. These changes we interpret as pain activation. It may be concluded that changes in rCBF are not likely to play a pathophysiological role in the development of cluster headache attacks.

Cluster headache is a rare headache entity that predominantly occurs in younger males. The clinical features are characterized by sudden attacks of unilateral excruciating pain localized periorbitally, associated with ipsilateral autonomic symptoms. The attacks occur in periods: clusters. The pathophysiology is still unknown. Such vasodilating substances as histamine, nitroglycerin and alcohol may provoke attacks. These substances may be used as diagnostic tests, but the interpretation of a negative result must be careful, as the attacks can not be induced in a refractory period after spontaneous occurrence, or at the beginning and end of cluster periods. As symptomatic treatment, ergotamine is the drug of first choice. High attack frequency may lead to overconsumption with ergotisme and further increased frequency. In such cases and for nocturnal attacks, oxygen inhalations represent an alternative. As prophylactic treatment ergotamine, methysergide, lithium and prednisone have proved efficacious. Most patients benefit from such treatment and may become virtually free from attacks. It is, therefore, important to differentiate this headache entity from classical migraine, common migraine and trigeminal neuralgia.