Cluster Headache: What's New?

BACKGROUND: Cluster headache is a highly disabling primary headache disorder which is widely described as the most painful condition a human can experience. AIM: To provide an overview of the clinical characteristics, epidemiology, risk factors, differential diagnosis, pathophysiology and treatment options of cluster headache, with a focus on recent developments in the field. METHODS: Structured review of the literature on cluster headache. RESULTS: Cluster headache affects approximately one in 1000 of the population. It is characterised by attacks of severe unilateral head pain associated with ipsilateral cranial autonomic symptoms, and the tendency for attacks to occur with circadian and circannual periodicity. The pathophysiology of cluster headache and other primary headache disorders has recently become better understood and is thought to involve the hypothalamus and trigeminovascular system. There is good quality evidence for acute treatment of attacks with parenteral triptans and high flow oxygen; preventive treatment with verapamil; and transitional treatment with oral corticosteroids or greater occipital nerve injection. New pharmacological and neuromodulation therapies have recently been developed. CONCLUSION: Cluster headache causes distinctive symptoms, which once they are recognised can usually be managed with a variety of established treatments. Recent pathophysiological understanding has led to the development of newer pharmacological and neuromodulation therapies, which may soon become established in clinical practice.

Cluster headache.

Cluster headache is an excruciating, strictly one-sided pain syndrome with attacks that last between 15 minutes and 180 minutes and that are accompanied by marked ipsilateral cranial autonomic symptoms, such as lacrimation and conjunctival injection. The pain is so severe that female patients describe each attack as worse than childbirth. The past decade has seen remarkable progress in the understanding of the pathophysiological background of cluster headache and has implicated the brain, particularly the hypothalamus, as the generator of both the pain and the autonomic symptoms. Anatomical connections between the hypothalamus and the trigeminovascular system, as well as the parasympathetic nervous system, have also been implicated in cluster headache pathophysiology. The diagnosis of cluster headache involves excluding other primary headaches and secondary headaches and is based primarily on the patient's symptoms. Remarkable progress has been achieved in developing effective treatment options for single cluster attacks and in developing preventive measures, which include pharmacological therapies and neuromodulation.

[Positioning of headache units in the field of neurology: the importance of OnabotulinumtoxinA and other therapies in the treatment of headaches]. / Posicionamiento de las unidades de cefalea en el ambito de la neurologia: la importancia de la OnabotulinumtoxinA y otras terapias en el tratamiento de la cefalea.

Chronic migraine is a disease that affects 0.5-2.5% of the population, depending on the statistics that are analysed and the definition of chronic migraine that is used. It is extraordinarily disabling, since it does not allow the sufferer to carry out any of their scheduled personal, professional or social activities, and it has a great impact on the patients' quality of life, as measured on disability, quality of life and impact on daily activities scales. Yet, nowadays there are treatments that have proven to be effective in cases of chronic migraine, such as OnabotulinumtoxinA. It is a treatment that is well tolerated and with a high rate of efficacy. Yet it is not only a therapeutic tool, but in the world of headaches it has also opened up the doors to invasive treatments, to the learning of techniques and, in short, to placing headaches in referral units that are usually located in tertiary care hospitals. Furthermore, it has also helped to overcome the idea that patients with headache should be visited exclusively by primary care physicians or general neurologists. This is an opportunity to redefine the field of study and the care for headaches that must be seized. In the future, this is going to be complemented by novel treatments with neurostimulation and probably with monoclonal antibodies against the calcitonin gene-related peptide. A revolution has begun in our knowledge and capacity to act. It is our duty to give it the importance and usage it deserves both for our patients and for us as specialists.

TITLE: Posicionamiento de las unidades de cefalea en el ambito de la neurologia: la importancia de la OnabotulinumtoxinA y otras terapias en el tratamiento de la cefalea.La migraña cronica es una enfermedad que afecta al 0,5-2,5% de la poblacion segun las estadisticas que se analicen y la definicion de migraña cronica que se adopte. Es extraordinariamente incapacitante, ya que no permite realizar las actividades personales, profesionales o sociales programadas, y tiene un gran impacto sobre la calidad de vida de los pacientes, medido en escalas de discapacidad, calidad de vida e impacto en la actividad diaria. Sin embargo, actualmente se dispone de tratamientos que han demostrado eficacia en la migraña cronica, como la OnabotulinumtoxinA. Es un tratamiento bien tolerado y con una tasa de eficacia elevada. Pero no es solo una herramienta terapeutica, sino que ha abierto las puertas en el mundo de la cefalea a la realizacion de tratamientos invasivos, al aprendizaje de tecnicas y, en definitiva, a situar la cefalea en unidades de referencia ubicadas, habitualmente, en hospitales de tercer nivel. Ademas, ha ayudado a eliminar el concepto de que los pacientes con cefalea deben ser atendidos exclusivamente por medicos de atencion primaria o neurologos generales. Esta es una oportunidad que debe aprovecharse para redimensionar el campo del estudio y asistencia de la cefalea. En el futuro, esto va a complementarse con novedosos tratamientos con neuroestimulacion y, probablemente, con anticuerpos monoclonales contra el peptido relacionado con el gen de la calcitonina. Se ha iniciado una revolucion en nuestro conocimiento y capacidad de actuacion. Es nuestro deber darle la importancia y uso que se merecen tanto para nuestros pacientes como para nosotros como especialistas.

Strictly unilateral headaches: considerations of a clinician.

The aim of the lecture is to draw attention to the role that clinical practice and clinical observation have had in stimulating research on the pathophysiology of cluster headache (CH) and other trigeminal autonomic cephalalgias (TACs). The symptoms of cluster headache-in particular the typical circadian periodicity of the headaches and the seasonal recurrence of cluster periods-were fundamental in shifting attention away from peripheral pathogenetic hypotheses to the idea that cluster headache could have a central origin. Initially, solid neuroendocrinological data pointed to hypothalamic involvement. For example, CH patients were shown to have alterations in biorhythms. Subsequently, modern functional neuroimaging techniques were able to demonstrate that the homolateral posterior hypothalamus is activated during TAC headaches, so implicating this region in TAC pathogenesis. It is known that the hypothalamus has a modulatory effect on nociceptive and autonomic pathways, particularly on the nociceptive trigeminovascular system. Future research should clarify whether the hypothalamus is the generator of TAC headaches, or whether it is activated in response to an alteration of the homeostatic equilibrium between limbic emotional-affective components and autonomic-nociceptive components modulated by the hypothalamus.

Use of cannabis among 139 cluster headache sufferers.

AIMS: A case report suggested the efficacy of cannabis to treat cluster headache (CH) attacks. Our aims were to study the frequency of cannabis use in CH patients, and the reported effects on attacks. METHODS: A total of 139 patients with CH attending two French headache centers filled out questionnaires. RESULTS: Sixty-three of the 139 patients (45.3%) had a history of cannabis use. As compared to nonusers, cannabis users were more likely to be younger (p < 0.001), male (p = 0.002) and tobacco smokers (p < 0.001). Among the 27 patients (19.4% of the total cohort) who had tried cannabis to treat CH attacks, 25.9% reported some efficacy, 51.8% variable or uncertain effects, and 22.3% negative effects. CONCLUSIONS: Cannabis use is very frequent in CH patients, but its efficacy for the treatment of the attacks is limited. Less than one third of self-reported users mention a relief of their attacks following inhalation. Cannabis should not be recommended for CH unless controlled trials with synthetic selective cannabinoids show a more convincing therapeutic benefit.

Aggressiveness in different presentations of cluster headache: results from a controlled multicentric study.

BACKGROUND: The hypothalamus has been discussed as a pivotal structure for both cluster headache (CH) and aggressiveness, but little is known about the extent of self-reported aggressiveness in patients with CH. PATIENTS AND METHODS: Twenty-six patients with chronic, 25 with active episodic and 22 with episodic CH outside the active period were examined interictally with a validated questionnaire quantifying factors of aggression and compared with 24 migraine patients and 31 headache-free volunteers. RESULTS: The ANOVA was significant for the subscale 'self-aggression/depression' (F(4, 123) = 5.771, p < 0.001) with significant differences between chronic and episodic CH and healthy volunteers. No significant changes were found for other subscales and the sum scale (F(4, 123) < 1.421, p > 0.230). Especially in the clinically most affected group of patients (chronic CH and active episodic CH), high levels of "self-aggression/depression" correlate with higher prevalence of depressive symptoms and higher impairment measured on an emotional and functional level. DISCUSSION: Self-aggressive and depressive cognitions with highest scores in chronic CH seem to be reactive as they correlate with depressive symptoms and impairment. They should be considered as an important therapeutic target since they impair the patient's life significantly.

Cluster headache and the hypothalamus: causal relationship or epiphenomenon?

Typical clinical features of cluster headache (CH) include circadian/circannual rhythmicity and ipisilateral cranial autonomic features. This presentation has led to the assumption that the hypothalamus plays a pivotal role in this primary headache disorder. Several studies using neuroimaging techniques or measuring hormone levels supported the hypothesis of a hypothalamic involvement in the underlying pathophysiology of CH. Animal studies added further evidence to this hypothesis. Based on previous data, even invasive treatment methods, such as hypothalamic deep brain stimulation, are used for therapy. However, the principal question of whether these alterations are pathognomonic for CH or whether they might be detected in trigeminal pain disorders in general, in terms of an epiphenomenon, is still unsolved. This article summarizes studies on hypothalamic involvement in CH pathophysiology, demonstrates the involvement of the hypothalamus in other diseases and tries to illuminate the role of the hypothalamus based on this synopsis.

Mode of occurrence of traumatic head injuries in male patients with cluster headache or migraine: Is there a connection with lifestyle?

INTRODUCTION: Our study objective was to investigate the mode of occurrence of traumatic head injury in episodic cluster headache and migraine patients. METHODS: We conducted a retrospective study on 400 male patients, 200 with cluster headache (cases) and 200 with migraine (controls). We investigated the frequency and mode of occurrence of traumatic head injury and some lifestyle habits. RESULTS: The number of traumatic head injuries was significantly higher in cases than in controls (adjusted odds ratio [OR] = 2.0; 95% confidence interval [CI] = 1.5-2.8). Cases were more often responsible for the head traumas (adjusted OR = 2.6; 95% CI = 1.3-4.9) and reported a significantly higher proportion of injuries during scuffles or brawls (OR = 6.5; 95% CI = 2.9-14.8). Compared with other cluster headache patients, cases responsible for traumatic head injuries were more frequently heavy alcohol (p = .000), heavy tobacco (p = .03) and heavy coffee consumers (p = .003). CONCLUSIONS: Cluster headache patients (a) had traumatic head injuries more frequently than migraineurs; and (b) were more often responsible for them, perhaps due to particular behaviours related to their lifestyles.

Use of complementary and alternative medicine by patients with cluster headache: results of a multi-centre headache clinic survey.

OBJECTIVES: To evaluate the rates, pattern, satisfaction with, and presence of predictors of complementary and alternative medicine (CAM) use in a clinical population of patients with cluster headache (CH). DESIGN AND SETTING: One hundred CH patients attending one of three headache clinics were asked to undergo a physician-administered structured interview designed to gather information on CAM use. RESULTS: Past use of CAM therapies was reported by 29% of the patients surveyed, with 10% having used CAM in the previous year. Only 8% of the therapies used were perceived as effective, while a partial effectiveness was reported in 28% of CAM treatments. The most common source of recommendation of CAM was a friend or relative (54%). Approximately 62% of CAM users had not informed their medical doctors of their CAM use. The most common reason for deciding to try a CAM therapy was that it offered a "potential improvement of headache" (44.8%). Univariate analysis showed that CAM users had a higher income, had a higher lifetime number of conventional medical doctor visits, had consulted more headache specialists, had a higher number of CH attacks per year, and had a significantly higher proportion of chronic CH versus episodic CH. A binary logistic regression analysis was performed and two variables remained as significant predictors of CAM use: income level (OR=5.7, CI=1.6-9.1, p=0.01), and number of attacks per year (OR=3.08, CI=1.64-6.7, p<0.0001). CONCLUSION: Our findings suggest that CH patients, in their need of and quest for care, seek and explore both conventional and CAM approaches, even though only a very small minority finds them very satisfactory.

Cluster headache: the history of the Cluster Club and a review of recent clinical research.

In September 2003, a scientific meeting was held in Rome to revive the International Cluster Headache Research Group (or "Cluster Club") tradition. This group of specialists was originally formed in the late 1970s by Ottar Sjaastad in order to promote research ideas, and to generate papers and other important information in this field. Its meetings, the last of which had taken place in 1994, had been informal events at which there was ample time for lively discussion. The last decade of the 20th century brought a significant increase in clinical and experimental research into cluster headache (CH), and this review summarizes some of the results of this research. The male preponderance of CH has been shown to be progressively decreasing over the years. Revised clinical criteria and a modern classification have been presented. First-degree relatives of probands with CH have been shown to have an increased risk of suffering from CH compared with the general population. Genetic analysis suggests that an autosomal dominant gene plays a role in some families. Functional neuroimaging has contributed to a better understanding of the pathophysiology of the condition. Positron emission tomography during provoked attacks has shown activation of the ipsilateral inferior posterior hypothalamus and it has been suggested that CH might be a functional neurovascular disorder of pacemaker or circadian regions in the hypothalamic grey matter. Subcutaneously administered sumatriptan has emerged as a highly effective acute treatment, but, in our opinion, the emphasis should be on attack prevention. Deep brain stimulation of the inferior posterior hypothalamic grey matter seems to be very promising as a novel treatment targeting the presumed central origin of pain attacks.

Update on cluster headache.

PURPOSE OF REVIEW: Although cluster headache has traditionally been thought of as a vascular headache disorder, its periodicity suggests an involvement of central areas such as the hypothalamus. This review covers the past 3 years, which have seen remarkable progress in understanding the pathophysiology of circadian headache syndromes and have brought exciting news. RECENT FINDINGS: As more cluster headache patients are seen by headache specialists, new forms of this well-defined primary headache syndrome are being identified. In addition, we discuss recent findings with regard to abnormalities in the secretion of hormones, genetic influences, neuroimaging of cluster headache attacks, and the use of newer substances as preventive therapy in cluster headache. SUMMARY: We have entered a new diagnostic and therapeutic era in primary headache disorders. In recent reports, the use of deep brain stimulation of the hypothalamus has enabled intractable chronic cluster headache patients to be successfully operated upon. Further research in this field is urgently needed and the recent possibility of combining deep brain stimulation with positron emission tomography will certainly help to unravel the brain circuitry implicated in stimulation-produced analgesia. The time has come to use the evidence for a disorder of circadian rhythm in cluster headache to further the development of chronobiotics in the treatment of this disorder.

Primary and secondary chronic cluster headache: two separate entities?

The International Headache Society (IHS) classification divides chronic cluster headache (CH) into two subtypes: chronic CH unremitting from onset (CCHU) and chronic CH evolved from episodic (CCHE). The purpose of our study was to point out any similarities and differences between the two chronic CH subtypes and to determine whether or not they can be considered as two separate clinical entities. We reviewed data about 31 CCHE patients and 38 CCHU patients referred to the Parma Headache Centre between 1975 and 1999. Clinically, CCHE patients exhibited statistically significant differences from CCHU patients, i.e. earlier CH onset and duration of attacks varying more frequently between 120 and 180 min. From the point of view of lifestyle, heavy alcohol and coffee drinkers prevailed among CCHU patients, while CCHE patients were more frequently heavy smokers. Based on clinical features, it seems reasonable to suppose that chronic CH may occur as two distinct entities.

Possible predictive factors in the evolution of episodic to chronic cluster headache.

The purpose of our study was to identify general factors and distinctive clinical features differentiating patients with chronic cluster headache (CH) evolved from episodic CH and patients with episodic CH. Our study sample included 28 patients suffering from chronic CH evolved from episodic CH and 258 patients with episodic CH; all were referred to the Headache Center of Parma between December 1975 and June 1998. Patients with episodic CH were selected from all episodic CH referrals (n = 485) and selection was based on the duration of the disorder, which was to exceed the average period needed for an episodic form to turn into a chronic form (4.5 years for females and 7.0 years for males). At CH onset, the mean age for patients with chronic CH evolved from episodic CH was older than for those with episodic CH. Among patients with chronic CH, more were smokers or heavy drinkers, and had suffered a head injury. Clinically, episodic CH evolving into chronic CH was characterized by a high frequency of cluster periods, a larger proportion of patients with attacks not occurring strictly within cluster periods, and remission periods lasting less than 6 months. Possible predictive factors in the development of chronic CH appear to be CH onset from the third decade of life onward, the occurrence of more than one cluster period a year, and the short-lived duration of remission periods. The role played by head injury and cigarette smoking in the evolution of the disorder still cannot be established with certainty.