Abstract
Introduction
This special collection of Cephalalgia is dedicated to cluster headache and the other trigeminal autonomic cephalalgias (TACs). It is part of an initiative which was started by the Board of the International Headache Society some years ago to improve awareness of and activities for cluster headache. This decision was the consequence of the observation that cluster headache has always been neglected when compared to migraine. Cluster headache is not a rare disorder although its prevalence and that of the other TACs is much lower than the prevalence of migraine. These disorders are often devastating and impairing primary headache disorders, which deserve the full attention of research and clinical medicine.
Historical remarks
Even in early history, cluster headache was only rarely described while migraine was already well recognized. There are no reports on cluster headache in antiquity whereas migraine has already been described in the Corpus Hippocraticum (starting around 500 BC). The first clinical description of cases of cluster headache was published by Nicolaes Tulp (original Claes Pieterszoon, 1593–1674 in Amsterdam) in his textbook Observationes medicae in 1641 (1). The first description of cluster headache as a disorder and of the periodicity of cluster headache was published by Thomas Willis (1621–1675) in his textbook De anima brutorum in 1672 (2). The first description of probable paroxysmal hemicrania was published as Dissertatio medica inauguralis de hemicrania horologica in Magdeburg in 1747 by the physician Johann Christoph Ulrich Oppermann.
In the more modern history of the 20th century, the first description of cluster headache was given by Robert Bing (1878–1956, Basle) in his German textbook Lehrbuch der Nervenkrankheiten (1913), where he defined this condition as erythromelalgia of the face or as erythroprosopalgia (3). The next milestone was the first complete description of cluster headache as a disorder separate from typical migraine by the neurologist Wilfred Harris (1869–1960) in London. He regarded cluster headache as a subtype of migrainous neuralgia and called it ciliary neuralgia. He treated some patients successfully with an injection of alcohol at the infraorbital nerve and with subcutaneous ergotamine tartrate (4). Bayard T. Horton (1895-1980) was the first to describe cluster headache in the United States (USA) and called it erythromelalgia of the head (1939) and later histaminic cephalgia (1952), and he treated cluster headache with histamine (5,6).
The modern term cluster headache was first used by E. Charles Kunkle (1952), although he thought that cluster headache was a subtype of migraine (7). Cluster headache was integrated into the Headache Classification of the Ad-hoc-Committee in the USA (1962) in the chapter of vascular headaches (8). In the International Classification of Diseases (ICD) published by the World Health Organization, 10th edition, cluster headache was called Bing-Horton-Headache. In the ICD, 11th edition, this was changed to cluster headache.
Cluster headache has been included since the first edition of the International Classification of Headache Disorders (ICHD-1). The diagnostic criteria of cluster headache and its subtypes evolved in the next iterations of ICHD. A clear example is represented by the cut-off adopted for remission period to distinguish between the episodic and the chronic phenotypes, which was increased from a minimum of 14 days to a minimum of three months.
The other TACs were all first described as an entity and as a disorder by Ottar Sjaastad (1928–2022). He first published on paroxysmal hemicrania in 1974 (9), then on short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) syndrome in 1978 (10), and then on hemicrania continua in 1984 (11). The term TAC as an overarching name for these disorders was introduced by Peter Goadsby and Richard Lipton in 1997 (12).
Current research and clinical findings
In this issue, we are happy to present the up-to-date information on research and clinical findings of all TACs. Kim et al. focus on the epidemiology and clinical aspects of cluster headache (13). Meanwhile we have stable data on the prevalence and on the burden of cluster headache, and the clinical features are well known. Although there are some minor regional differences with respect to accompanying symptoms, the core features of cluster headache are very similar and very stable worldwide suggesting that this is a hereditary somatic brain disorder. The contribution by Belin and Barloese focuses on the aspects of genetics and on the striking chronobiology of cluster headache (14). The first relevant advances have been made in this field, in particular in genetical mapping. The authors provide a nice overview of the genes involved in chronobiology and sleep homeostasis and how their alteration may explain specific features of cluster headache.
Coppola et al. summarize the current knowledge on the pathophysiology of cluster headache (15). This includes the role of CGRP, the role of the hypothalamus, and the role of the trigeminovascular system. They also provide a critical appraisal of neurophysiological and neuroimaging data to disentangle the role of specific brain areas as well as of wider cerebral networks. Differences between migraine and cluster headache are elucidated showing that these two headache disorders may represent separate entities. Finally, Peng and Burish present the current evidence-based treatment which is separated into acute and prophylactic drug treatment and non-pharmacological treatment (16). Truly, since the introduction of subcutaneous sumatriptan for acute attack treatment of cluster headache in 1991, no specific advances have been made in the treatment of cluster headache. Even the new anti-CGRP antibodies which are so helpful in migraine are of poor efficacy in cluster headache, at least in the dosage given in the clinical trials. However, most patients can be treated effectively according to the recent treatment guidelines, e.g. published by the European Academy of Neurology (17).
Two articles are dedicated to the other TACs, one to hemicrania continua and paroxysmal hemicrania and one to SUNCT/SUNA syndrome. The first one by Bahra detailed several features of the so-called indomethacin-responsive TACs (18). She also comments on those headaches with a clinical picture suggestive for hemicrania continua or paroxysmal hemicrania, but without a clearcut response to indomethacin. These entities represent a diagnostic challenge for headache specialists and deserve attention from the scientific community. Finally, the paper by Kang and Cho provides a comprehensive overview of pathophysiological, clinical, and therapeutic aspects of SUNCT and SUNA (19). This group of TACs received scientific attention due to the debate on whether there are differences between SUNCT and SUNA or if they represent a single disease, namely short-lasting unilateral neuralgiform headache attacks (SUNHA). However, this was an academic debate without impact on the treatment. Particularly for these syndromes, efficacious treatment strategies are greatly needed.
Perspectives
We believe that cluster headache deserves more awareness in neurology, in pain medicine, and also in general medicine to make the correct diagnosis in an early stage of the disorder and to treat according to existing guidelines. Despite recent advances, diagnostic delay is still more than 10 years in over 20% of patients suffering from cluster headache. Research should be stimulated by the enormous burden caused by cluster headache and by ourselves as researchers in the field. Industry should be encouraged to perform clinical trials on cluster headache, guidelines on how to design such trials have recently published (20).
We have seen tremendous efforts to improve the treatment of migraine in the last decades. We have also seen, for example, tremendous efforts to improve the treatment of multiple sclerosis, a disorder with nearly the same worldwide prevalence as cluster headache, namely 0.1%. If we put more public and scientific focus on cluster headache, as it has been done in the past for multiple sclerosis, we could succeed in a better treatment for our patients.
