CLUSTER

Cluster headache (CH), also known as "suicide headache," is characterized by a distinctive behavior during attacks. In 80% to 90% of cases, patients are restless and constantly moving in a vain attempt to relieve pain. They often perform complex, stereotyped actions. During attacks, CH sufferers do not want to be touched, stroked, or comforted and frequently moan a great deal, cry, or even scream. They sometimes indulge in violent, self-hurting behavior. Restlessness is a highly sensitive and highly specific parameter for CH and has been included among the signs and symptoms accompanying pain of the disorder in the Second Edition of the International Classification of Headache Disorders. A few hypotheses on pathophysiology of restlessness are addressed in this paper.
Comments: The IHCD-II added "a sense of restlessness or agitation" to the 'C' criteria for the diagnosis of cluster, symptoms from which at least one is necessary. The other 'C' criteria are dysautonomic signs, but the addition of agitation adds emphasis to the prominence of this manifestation of cluster.—Stewart J. Tepper, MD
Given the postulated involvement of hypothalamic nuclei in cluster and the stereotyped nature of the behavior, perhaps this could be considered the behavioral correlate of autonomic activity?—David S. Millson, MD     

Chronic cluster headache: a review

Cluster headache (CH) is a rare but severe headache disorder characterised by repeated unilateral head pain attacks accompanied by ipsilateral autonomic features. In episodic CH, there are periods of headache attacks with pain–free intervals of weeks, months or years in between. A minority of patients have the chronic form, without pain–free intervals between the headache attacks. Chronic CH can occur as primary or secondary chronic CH; the rarest form is episodic CH arising from chronic CH. In this article, we give a review of the chronic forms of CH and focus on demographics, clinical manifestations, social habits, predictive factors, head injury, genetics, neuroimaging and therapy. It is remarkable that little is known about risk factors that make CH chronic.     

Cataract in chronic cluster headache: two case reports and review of the literature

Cluster headache (CH) consists of attacks of severe, unilateral orbital/supraorbital/temporal pain, lasting for 15–180 min, occurring once or more times a day, and associated with ipsilateral conjunctival injection, lacrimation and other symptoms. Cataract is clouding of the lens of the eye causing a progressive and painless loss of vision. We describe the cases of two men (not relative, but with the same last name, which originates from north-eastern Italy) that in young adult age, after years of suffering from chronic CH, developed cataract on the same side of the pain attacks. Patient 1 was diagnosed as having cataract 18 years after the onset of episodic (and subsequently chronic) CH. Patient 2 began suffering from chronic CH at the age of 44 years and after 8 years he developed cataract. This is the first report of cataract in patient suffering of CH and occurring in the eye affected by the pain attack. No financial support received.     

Cluster headache and SUNCT: similarities and differences

SUNCT is probably a distinct syndrome, although it shares some common features with cluster headache (CH): male sex preponderance, clustering of attacks, unilaterality of headache without sideshift, pain of non-pulsating type with its maximum in the periocular area, ipsilateral autonomic phenomena (e.g. conjunctival injection, lacrimation, rhinorrhea, increased forehead sweating), systemic blood pressure increment with heart rate decrement, blood flow velocity decrement in the middle cerebral artery, and hyperventilation. In spite of these similarities, SUNCT syndrome differs clearly from CH as regards a number of clinical variables, such as duration, intensity, frequency, and nocturnal preponderance of attacks. The two syndromes also differ markedly as regards precipitation of attacks, the usual age at onset, and efficacy of various treatment alternatives. Laboratory investigations have disclosed differences as regards presence or absence of Horner-like picture and possibily also the respiratory sinus arrhythmia pattern. All in all, these differences seem sufficiently ponderous to make it likely that SUNCT syndrome and CH differ essentially. SUNCT seems to be a “neuralgiform” headache, but different from trigeminal neuralgia. Received: 2 April 2001 / Accepted: 23 July 2001     

Chronic cluster headache: New and emerging treatment options

Cluster headache (CH) is a primary headache syndrome characterized by short-lasting unilateral head pain attacks accompanied by ipsilateral oculofacial autonomic phenomena. Approximately 20% of CH patients have the chronic form and need continuous medical care. In the chronic form, attacks continue unabated for years, often on a daily basis, resulting in severe debilitation. It is a common experience that drug treatments are able to control or prevent the attacks in approximately 80% of chronic CH patients. In the remaining 20% of chronic cases, drugs are ineffective. Until recently, the etiology of CH was poorly understood and this hampered the development of new therapies. However, we have now gained a much improved understanding of the peripheral and central mechanisms giving rise to the pain in CH and this has inspired the development of new treatment approaches, which, although still in the initial phases of validation, appear to be very promising. Among these, the novel approach based on hypothalamic deep brain stimulation is one of the most promising.     

The Primary Headaches as a Reflection of Genetic Darwinian Adaptive Behavioral Responses

(Headache 2010;50:273‐289) Objective.— The objective of this study is to present a view of the primary headaches as genetically determined behavioral responses consistent with sickness behavior and defense reaction, respectively. Background and Design.— A review of the literature bearing on the behavioral, humoral, and functional imaging aspects of the primary headaches shows that migraine and cluster headache (CH) are pain conditions characterized by different behaviors during the attacks. Here it is postulated that the behavioral responses to migraine and CH are evolutionary conserved reactions consistent with sickness behavior and defense reaction. Results.— The sickness behavior observed during migraine attacks is a pan‐mammalian adaptive response to internal and external stressors, characterized by withdrawal and motor quiescence, sympatho‐inhibition and lethargy, in which visceral pain signals a homeostatic imbalance of the body and/or brain. In contrast, the defense reaction in CH consists of a fight‐or‐flight reaction, with motor restlessness and agitation, in which pain is exteroceptive in kind. Conclusion.— These different behavioral responses are thus specific to different kinds of pain, distinguished by the behavioral significance of the pain (visceral pain in migraine vs exteroceptive pain in CH), and imply brain matrices involving different networks in the brainstem, hypothalamus, and forebrain regions that engender evolutionarily conserved adaptive genetic responses. Cytokines play an important role in their development. Predictions and limitations of the hypothesis are discussed together with implications for genetic studies on headaches.     

Cluster Belly: A Variant of Irritable Bowel Syndrome

Cluster headache (CH) and irritable bowel syndrome (IBS) are pain disorders that possess relationships with circadian rhythms. However, they have not been compared to assess similarities that could yield pathophysiologic insights. A young male adult with periodic episodes of abdominal pain highly reminiscent of CH is described. Since childhood, he experienced severe attacks featuring excruciating, abdominal pain accompanied by prominent restlessness, lasting 30‐120 minutes, occurring in the evening and in discrete 2‐ to 8‐week periods, interspersed with remissions where typical triggers did not lead to attacks. Although all of the patient's symptoms fell within the spectrum of IBS, the semiology was highly evocative of CH, based on the attack duration, restlessness, periodicity, and selective vulnerability to particular triggers only during attack periods. A subset of patients thought to have IBS may feature similar attack profiles and could suggest the importance of the hypothalamus in its pathophysiology, akin to CH.     

Cluster headache--acute and prophylactic therapy

Cluster headache (CH) pain is the most severe of the primary headache syndromes. It is characterized by periodic attacks of strictly unilateral pain associated with ipsilateral cranial autonomic symptoms. The majority of patients have episodic CH, with cluster periods that typically occur in a circannual rhythm, while 10% suffer from the chronic form, with no significant remissions between cluster periods. Sumatriptan injection or oxygen inhalation is the first-line therapy for acute CH attacks, with the majority of patients responding to either treatment. The calcium channel blocker verapamil is the drug of choice for CH prevention. Other drugs that may be used for this purpose include lithium carbonate, topiramate, valproic acid, gabapentin, and baclofen. Transitional prophylaxis, most commonly using corticosteroids, helps to control the attacks at the beginning of a cluster period. Peripheral neural blockade is effective for short-term pain control. Recently, the therapeutic options for refractory CH patients have expanded with the emergence of both peripheral (mostly occipital nerve) and central (hypothalamic) neurostimulation. With the emergence of these novel treatments, the role of ablative surgery in CH has declined.     

Behavioral Response to Headache: A Comparison Between Migraine and Tension-type Headache

OBJECTIVE: To compare patients with migraine and tension-type headache in their behavior during the attacks and the maneuvers used to relieve the pain. BACKGROUND: Patients with headache often perform nonpharmacological measures to relieve the pain, but it is not known if these behaviors vary with the diagnosis, clinical features, and pathogenesis. METHODS: One hundred consecutive patients with either migraine (n = 72 ) or tension-type headache (n = 28) were questioned (including the use of a checklist) concerning their usual behavior during the attacks and nonpharmacological maneuvers performed to relieve the pain. The results of the two types of headache were compared. RESULTS: Patients with migraine tended to perform more maneuvers than individuals with tension-type headache (mean, 6.2 versus 3). These maneuvers included pressing and applying cold stimuli to the painful site, trying to sleep, changing posture, sitting or reclining in bed (using more pillows than usual to lay down), isolating themselves, using symptomatic medication, inducing vomiting, changing diet, and becoming immobile during the attacks. The only measure predominantly reported by patients with tension-type headache was scalp massage. However, the benefit derived from these measures was not significantly different between the two groups (except for a significantly better response to isolation, local pressure, local cold stimulation, and symptomatic medication in migraineurs). CONCLUSIONS: The behavior of patients during headache attacks varies with the diagnosis. Measures that do not always result in pain relief are performed to prevent its worsening or to improve associated symptoms. These behavioral differences may be due to the different pathogenesis of the attacks or to different styles of dealing with the pain. They can also aid the differential diagnosis between headaches in doubtful cases.     

Electrical Stimulation of Sphenopalatine Ganglion for Acute Treatment of Cluster Headaches

(Headache 2010;50:1164‐1174) Introduction.— Cluster headaches (CH) are primary headaches marked by repeated short‐lasting attacks of severe, unilateral head pain and associated autonomic symptoms. Despite aggressive management with medications, oxygen therapy, nerve blocks, as well as various lesioning and neurostimulation therapies, a number of patients are incapacitated and suffering. The sphenopalatine ganglion (SPG) has been implicated in the pathophysiology of CH and has been a target for blocks, lesioning, and other surgical approaches. For this reason, it was selected as a target for an acute neurostimulation study. Methods.— Six patients with refractory chronic CH were treated with short‐term (up to 1 hour) electrical stimulation of the SPG during an acute CH. Headaches were spontaneously present at the time of stimulation or were triggered with agents known to trigger clusters headache in each patient. A standard percutaneous infrazygomatic approach was used to place a needle at the ipsilateral SPG in the pterygopalatine fossa under fluoroscopic guidance. Electrical stimulation was performed using a temporary stimulating electrode. Stimulation was performed at various settings during maximal headache intensity. Results.— Five patients had CH during the initial evaluation. Three returned 3 months later for a second evaluation. There were 18 acute and distinct CH attacks with clinically maximal visual analog scale (VAS) intensity of 8 (out of 10) and above. SPG stimulation resulted in complete resolution of the headache in 11 attacks, partial resolution (>50% VAS reduction) in 3, and minimal to no relief in 4 attacks. Associated autonomic features of CH were resolved in each responder. Pain relief was noted within several minutes of stimulation. Conclusion.— Sphenopalatine ganglion stimulation can be effective in relieving acute severe CH pain and associated autonomic features. Chronic long‐term outcome studies are needed to determine the utility of SPG stimulation for management and prevention of CH.     

Oxygen therapy influences episodic cluster headache and related cutaneous brush and cold allodynia

Cluster headache (CH) is characterized by a series of sudden attacks of short-lasting severe headache pain with ipsilateral autonomic features, including lacrimation, rhinorrhea, localized sweating, eyelid edema, and partial or complete Horner's syndrome. Just like in migraine, brush allodynia has been described for CH and for short lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) syndrome. Administration of normobaric oxygen is part of the standard therapy for CH attacks. Here, we describe a young male with a first CH attack and the influence of oxygen on pain and concomitant cutaneous allodynia.     

Cluster headache, hypothalamus, and orexin

Cluster headache (CH) is a highly disabling condition resulting in severe, recurrent unilateral bouts of pain and accompanying autonomic symptoms. This review describes some current views regarding the underlying pathophysiology covering the pain and cranial autonomic (parasympathetic) activation, and highlights the potential importance of the hypothalamus in CH. The hypothalamus is known to modulate many functions and has been shown to be involved in the pathophysiology of a variety of primary headaches, including CH. Hypothalamic structures are likely to underlie the circadian and circannual periodicity of attacks and contribute to the pain and autonomic disturbances. We discuss the hypothalamic involvement in CH and modulation of trigeminovascular processing and examine the emerging involvement of the hypothalamic orexinergic system as a possible key pathway in CH pathophysiology.     

The electrophysiology of cluster headache

Cluster headache (CH) is a neurovascular headache disease characterized by recurrent, strictly unilateral, severe pain attacks. Despite its typical clinical features, including circadian rhythm of the attacks and ipsilateral autonomic dysfunction, the underlying pathophysiology of CH is still unclear. Electrophysiological data point to central disinhibition of the trigeminal nociceptive system as one of the key mechanisms of CH pain. Therefore, altered habituation pattern and changes within trigeminal-facial neuronal circuits due to central sensitization seem to be involved. One biochemical correlate is probably represented in dysfunctions of serotonergic raphe nuclei-hypothalamic pathways. Structural and functional imaging data show an alteration of hypothalamic structures in CH patients, supporting the hypothesis that the hypothalamus, according to its function as a circadian pacemaker, plays a pivotal role in CH pathology. Cortical and brainstem reflexes are reviewed to illuminate the pathophysiology of CH.     

Biological markers of cervicogenic headache

Upper cervical pain is frequent in different primary headaches and not sufficient evidence for cervicogenic headache (CH). Biological markers should help to differentiate CH from other headache disorders. In most cases, imaging techniques of the cervical spine are not helpful for the diagnosis of CH. Symptoms and signs of neck involvement, such as a mechanical precipitation of attacks, a restriction in range of motion of the cervical spine, and the existence of ipsilateral neck, shoulder, or arm pain, seem to be reasonably valid for the diagnosis of CH, but its reliability and validity should be confirmed in larger studies. Positive diagnostic blockades of cervical structures or its nerve supply are not specific for CH. Neurophysiological investigations give some insight into the pathophysiological mechanisms of CH but are not diagnostic. In CH, calcitonin gene-related peptide levels do not differ between the symptomatic and the asymptomatic side, between the jugular and the cubital blood, and between days with and without headache. There is no evidence for an activation of the trigeminovascular system in CH. It can be concluded that CH is not just a migraine variant triggered by neck dysfunction but a functional entity.     

Paroxysmal Hemicrania: An Update

Paroxysmal hemicrania (PH) is an underreported and underdiagnosed primary headache disorder. It usually begins in the third or fourth decade of life. The recent observations indicate that it is equally prevalent in both males and females. PH is characterized by severe, strictly unilateral head pain attacks that occur in association with ipsilateral autonomic features. The attacks in PH are shorter and more frequent compared with cluster headache (CH) but otherwise PH and CH have similar clinical features. The hallmark of PH is the absolute cessation of the headache with indomethacin. However, a range of drugs may show partial to complete relief in certain groups of patients. Neuromodulatory procedures, such as greater occipital nerve blockade, blockade of sphenopalatine ganglion and neurostimulation of the posterior hypothalamus, are reserved for refractory PH.     

SUNCT: a new case with some unusual features

A healthy 22–year–old man complained of primary stabbing headache (PSH) for about two months. The headache recurred after one year and after a month the pain took on the characteristics of short–lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT). This patient shows some unusual features: juvenile onset, miosis during attacks as part of autonomic phenomena and close temporal relationship with stressful events. The association between PSH and SUNCT may be interpreted as the coexistence of two different headaches or that the PSH is a forerunner to the SUNCT.     

Cold as an adjunctive therapy for headache

We report the results of a study conducted recently at the Diamond Headache Clinic, Chicago, on the effectiveness of application of cold as an adjunctive therapy for acute headache. Ninety clinic outpatients were divided evenly into three groups according to headache type--migraine, cluster, and mixed. They used the standard headache medication for two attacks and the standard medication plus application of cold with a reusable, frozen gel pack for two attacks. There was no significant difference in patient response to the gel pack by headache type. Seventy-one percent of patients considered the pack effective; 52% reported an immediate decrease in pain, and 63% reported an overall decrease in pain. Seventy-one percent of patients intended to use the gel pack in the future. Use of such gel packs, which are available commercially, does not damage the skin. Our study indicates that cold application does provide some symptomatic relief of headache; it may also offer psychological alleviation of the pain.     

Lessons from 8 years' experience of hypothalamic stimulation in cluster headache

Neuroimaging studies in cluster headache (CH) patients have increased understanding of attack-associated events and provided clues to the pathophysiology of the condition. They have also suggested stimulation of the ipsilateral posterior inferior hypothalamus as a treatment for chronic intractable CH. After 8 years of experience, stimulation has proved successful in controlling the pain attacks in almost 60% of chronic CH patients implanted at various centres. Although hypothalamic implant is not without risks, it has generally been performed safely. Implantation affords an opportunity to perform microrecordings of individual posterior hypothalamic neurons. These studies are at an early stage, but suggest the possibility of identifying precisely the target site by its electrophysiological characteristics. Autonomic studies of patients undergoing posterior hypothalamic stimulation provide further evidence that long-term stimulation is safe, revealing that it can cause altered modulation of the mechanisms of orthostatic adaptation without affecting the baroreflex, cardiorespiratory interactions or efferent sympathetic and vagal functions. Chronically stimulated patients have an increased threshold for cold pain at the site of the first trigeminal branch ipsilateral to the stimulated side; when the stimulator is switched off, changes in sensory and pain thresholds do not occur immediately, suggesting that long-term stimulation is required to induce sensory and nociceptive changes. Posterior inferior hypothalamic stimulation is now established as a treatment for many chronic CH patients. The technique is shedding further light on the pathophysiology of the disease, and is also providing clues to functioning of the hypothalamus itself.     

Placebo response in cluster headache trials: a review

Probably because of its relative rarity as primary headache, there are few well-controlled clinical trials on cluster headache (CH) patients. Due to the severity of the pain, the placebo response in CH has been considered to be small. During the eighties the first double-blind, placebo-controlled trials were reported, and placebo responses demonstrated. Here we review the placebo response in CH trials in order to assess its magnitude and consider how future studies can be optimized. Six trials were identified with a double-blind, placebo-controlled, cross-over design testing treatments of acute CH. For those with a primary endpoint set to no or mild headache the placebo responses varied from 7 to 42%. In five of seven prophylactic trials, using a double-blind, placebo-controlled, parallel-group design, the placebo was merely used to set a baseline for comparison. The placebo responses were reported in only two trials. Here the response varies from 14 to 43%, the lowest value was reported using the strict endpoint; cessation of headache attacks. We conclude that a placebo response exists in trials of drugs on CH patients. Furthermore, this placebo response is of the same magnitude as that seen in migraine studies. We recommend the use of IHS guidelines when designing new trials. The possibility of a genuine biological mechanism responsible for the placebo response is discussed.     

Migraine - Cluster Headache Syndrome

SYNOPSIS
The migraine-cluster headache syndrome is defined as headaches that are predominately of one type but with at least one major timing factor plus three lesser features of the other or five lesser features of the other (no more than one of the opposing features is a weak differential feature). The most important factors distinguishing migraine (M) from cluster headache (CH) are the timing of attacks (random occurrence versus clustering, frequency, duration, hour of onset) and the prodromal phenomena which occur with classical M, but are rarely seen with CH. Somewhat less significant differentiating characteristics are the associated symptoms of ipsilateral eye redness and tearing, nasal congestion and secretion, and partial Horner's syndrome which often accompany CH, in contrast to the symptoms of nausea and vomiting commonly associated with M. Also helpful in establishing the diagnosis are the quality, site and recurrent laterality of the pain, as well as its aggravating and ameliorating factors. Weak features in the differential diagnosis of M and CH are age of onset, sex, family history, and response to therapy.
Patients with M or CH seen at the Headache Unit of Montefiore Medical Center during the past two years were evaluated for the occurrence of the migraine-cluster headache syndrome. Nine (1.0%) of 923 patients with M had 4 or more features of CH and 5 (3.2%) of 154 patients with CH had 4 or 5 characteristics of M. In 4 patients symptoms of M and CH were blended in such a way neither headache predominated.