Acute Cluster Headache Attacks Research Articles

202 Placebo-controlled intravenous nitroglycerin phenotyping of acute attacks of cluster headache

IntroductionCluster headache (CH) is characterised by attacks of excruciating unilateral headache, ipsilateral cranial autonomic symptoms (CAS) and/or agitation. Nitroglycerin (NTG) is known to induce CH. This study is the first single-blind placebo-controlled study using intravenous NTG in CH to characterise comprehensively NTG induced CH attacks.MethodsCH patients attended three study visits in total, first visit CH patients were unblinded and received intravenous NTG 0.5mcg/kg/min over 20 minutes, if successful they were asked to return for blinded visits either receiving NTG or placebo. The clinical phenotype was recorded. The study was approved by the NHS Research Ethics Committee.ResultsThirty-three patients participated, 24 completed all study visits. Nineteen episodic cluster headache (58%) and 14 chronic cluster headache (42%). NTG brought on CH attacks (n= 26, 79%), agitation (n= 24, 73%) and CAS (n= 31, 94%) in the unblinded NTG visit. NTG brought on CH attacks (n= 19, 76%), agitation (n= 20, 80%) and CAS (n= 21, 84%) in the blinded NTG visit. Only one participant had a spontaneous CH attack (4%) in the placebo visits, four participants reported unilateral CAS symptoms, and none had agitation.ConclusionWe demonstrate that intravenous NTG effectively triggers CH attacks.diana.wei@kcl.ac.uk

Update on Treatment of Cluster Headache

Cluster headache (CH) is characterized by severe unilateral short-lasting headache attacks, accompanying ipsilateral cranial autonomic symptoms or the sense of restlessness and agitation, or both. CH is a highly disabling primary headache disorder but often not optimally treated. High-flow oxygen and parenteral triptans are the most effective treatment to treat an acute CH attack. Transitional treatments include systemic steroid therapy and sub-occipital steroid injection. For preventive therapy, verapamil and lithium are recommended as first-line treatments. Novel treatments have appeared, such as neuromodulation and medication targeting calcitonin gene-related peptide (CGRP) or its receptor. Galcanezumab, the only anti-CGRP receptor monoclonal antibody with proven efficacy for the preventive treatment of episodic CH, represents an important advance for pharmacological treatment of CH. Neuromodulation strategies, such as the non-invasive vagus nerve stimulation and the sphenopalatine ganglion stimulation, have been proven effective in reducing the intensity and frequency of attacks, and also to be safe and well tolerated.

The use of oxygen in cluster headache treatment worldwide - a survey of the International Headache Society (IHS).

Background Oxygen is recommended for the treatment of acute cluster headache attacks. However, it is not available worldwide. Methods The International Headache Society performed a survey among its national member societies on the availability and the restrictions for oxygen in the treatment of cluster headache. Results Oxygen is reimbursed in 50% of all countries responding ( n = 22). There are additional restrictions in the reimbursement of the facial mask and with respect to age. Conclusion Oxygen for the treatment of cluster headache attack is not reimbursed worldwide. Headache societies should pressure national/public health authorities to reimburse oxygen for cluster headache in all countries.

Peripheral neurostimulation in primary headaches.

Peripheral neurostimulation techniques have emerged as promising treatments for patients with medically intractable, highly disabling chronic daily headaches including chronic migraine (CM) and chronic cluster headache (CCH) besides other less common headache syndromes. Encouraging controlled and open label data in medically intractable CM and trigeminal autonomic cephalalgias (TACs) have suggested a meaningful therapeutic role for occipital nerve stimulation (ONS). In view of the frequent occurrence of pain in the first branch of trigeminal nerve, percutaneous supraorbital nerve stimulation alone or in combination with ONS has been used successfully in open label series of CM and CCH patients. In view of its connections with the trigeminovascular system, the stimulation of the sphenopalatine ganglion has been used as a therapeutic target for the treatment of acute cluster headache attacks, with promising results. Preliminary data in patients with epilepsy and migraine have suggested a potential efficacy of vagus nerve stimulation in the treatment of primary headaches. Non-invasive devices targeting peripheral nerves have been developed and initial experience is emerging for the acute and preventive treatments of primary headache disorders. This review analyses the available evidence on the efficacy and safety of the different peripheral neurostimulation techniques.

Stimulation of the sphenopalatine ganglion in intractable cluster headache: expert consensus on patient selection and standards of care.

Chronic cluster headache (CCH) is a debilitating headache disorder with a significant impairment of the patients' lives. Within the past decade, various invasive neuromodulatory approaches have been proposed for the treatment of CCH refractory to standard preventive drug, but only very few randomized controlled studies exist in the field of neuromodulation for the treatment of drug-refractory headaches. Based on the prominent role of the cranial parasympathetic system in acute cluster headache attacks, high-frequency sphenopalatine ganglion (SPG) stimulation has been shown to abort ongoing attacks in some patients in a first small study. As preventive effects of SPG-stimulation have been suggested and the rate of long-term side effects was moderate, SPG stimulation appears to be a promising new treatment strategy. As SPG stimulation is effective in some patients and the first commercially available CE-marked SPG neurostimulator system has been introduced for cluster headache, patient selection and care should be standardized to ensure maximal efficacy and safety. As only limited data have been published on SPG stimulation, standards of care based on expert consensus are proposed to ensure homogeneous patient selection and treatment across international headache centres. Given that SPG stimulation is still a novel approach, all expert-based consensus on patient selection and standards of care should be re-reviewed when more long-term data are available.

Changes in Plasma Methionine-Enkephalin Levels Associated With a Cluster Headache Episode

Eighteen male cluster headache (CH) inpatients within a CH series participated in this research. Blood samples were drawn from patients at least 6-hour pain-free after the last acute CH episode and then shortly prior (SP), during, and soon after (SA) a new acute CH attack. Three healthy male, age-comparable drug-free volunteers served as controls; 5 samples were obtained from each of these individual over a 24-hour period. Individual patient's methionine-enkephalin (MET) plasma concentration showed significant changes, and in some subjects, dramatic changes, during the different phases of a single CH episode. Peptide levels followed a general pattern of higher plasma concentration SP to an acute CH attack, followed by decreased levels during the attack itself, and falling even further SA the acute episode. Consistently, 16 of the 18 patients tested showed pre-CH peptide levels significantly higher (arbitrarily the authors considered values 20% or more as "significant") than their own values obtained during the acute CH pain phase, with observed differences reaching 80% or more in 7 of these individuals. For about half of these patients, peptide concentration during the acute CH episode was significantly above the control's range (68.2-87.6 pg MET/mL; control's circulating MET concentration remaining essentially unchanged during a 24-hour period). MET levels were further decreased in essentially all of the post-CH samples, with values falling within (n = 6) or even further below than those in the control's range (n = 11). Neither age, time of CH occurrence, nor patient's use of a number of medications known for failing to influence plasma MET degradation kinetics seemed to significantly influence MET levels. These results might help in the biochemical characterization of the actual phases of a CH episode. Developing drugs modulating MET bioavailability could lead to novel antinociceptive agents useful for the treatment of CH's associated pain.

Pearls and pitfalls: Neurostimulation in headache

A variety of neuromodulatory approaches available today has broadened our therapeutic options significantly especially in drug refractory patients with chronic cluster headache and chronic migraine. It is a dynamic field with a current trend to non-invasive transcutaneous stimulation approaches. However, sound studies providing evidence for the widespread use of these novel approaches are sparse. For invasive approaches, occipital nerve stimulation is now widely considered the treatment of first choice in chronic trigeminal autonomic cephalgias and - with limitations - chronic migraine. Although equally effective, deep brain stimulation is considered second-line treatment in cluster headache because of its potentially life-threatening side effects. Most recently, stimulation of the sphenopalatine ganglion has also been shown to effectively abort acute cluster headache attacks. Interesting other upcoming approaches include transcutaneous supraorbital nerve stimulation and transcutaneous vagal nerve stimulation. Pearls and pitfalls of common invasive and non-invasive neuromodulatory approaches and open questions are summarised in this review along with recommendations for future studies.

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.

MO10 Beta-oscillations in the posterior hypothalamus are associated with acute cluster headache attacks

MO10 Beta-oscillations in the posterior hypothalamus are associated with acute cluster headache attacks

The Use of Radiolabelled Human Serum Albumin and SPECT/MRI Co-Registration to Study Inflammation in The Cavernous Sinus of Cluster Headache Patients

A sterile inflammation in the cavernous sinus was hypothesized to underlie cluster headache (CH). Neurogenic inflammation is accompanied by the extravasation of plasma proteins in the surrounding tissue. We tested the hypothesis of an inflammatory process in the cavernous sinus in CH patients using 99mTc-human serum albumin (HSA) and single photon emission computed tomography (SPECT). Six patients with episodic CH were enrolled. After baseline imaging, CH attacks were induced by IV injection of nitroglycerin. The patients remained untreated for 20 min. A second SPECT was performed after successful treatment. Region of interest (ROI) analysis was performed on the basis of coregistered MRI/SPECT data. There was no statistical difference between the 99mTc-HSA uptake in the ipsilateral cavernous sinus before and after induction of an acute CH attack. There was no evidence for 99mTc-HSA extravasation in the cavernous sinus during the active episode as compared with the remission phase. Our results do not support the hypothesis of an inflammation in the cavernous sinus.

Hypothalamic Deep Brain Stimulation in Positron Emission Tomography

Recently, functional imaging data have underscored the crucial role the hypothalamus plays in cluster headache, one of the most severe forms of primary headache. This prompted the application of hypothalamic deep brain stimulation. Yet, it is not apparent how stimulation of an area that is thought to act as a pace-maker for acute headache attacks is able to prevent these attacks from occurring. We addressed this issue by examining 10 operated chronic cluster headache patients, using H2(15O)-positron emission tomography and alternately switching the hypothalamic stimulator on and off. The stimulation induced activation in the ipsilateral hypothalamic gray (the site of the stimulator tip), the ipsilateral thalamus, somatosensory cortex and praecuneus, the anterior cingulate cortex, and the ipsilateral trigeminal nucleus and ganglion. We additionally observed deactivation in the middle temporal gyrus, posterior cingulate cortex, and contralateral anterior insula. Both activation and deactivation are situated in cerebral structures belonging to neuronal circuits usually activated in pain transmission and notably in acute cluster headache attacks. Our data argue against an unspecific antinociceptive effect or pure inhibition of hypothalamic activity. Instead, the data suggest a hitherto unrecognized functional modulation of the pain processing network as the mode of action of hypothalamic deep brain stimulation in cluster headache.

Treatment of Cluster Headache Attacks With Less Than 6 mg Subcutaneous Sumatriptan

Subcutaneous (SQ) sumatriptan 6 mg is effective in the treatment of acute cluster headache attacks. However, patients sometimes benefit from a dose less than 6 mg. Therefore, we designed a prospective open study to evaluate how many patients benefit from a dose less than 6 mg SQ sumatriptan. We enrolled 81 consecutive patients with cluster headache and recorded their use of SQ sumatriptan and oxygen. Patients regularly using SQ sumatriptan 6 mg were advised to treat attacks with doses less than 6 mg and with oxygen. Efficacy and side effects of the different treatment options (6 mg, 3 mg, 2 mg, and oxygen) were evaluated. As a result, 74% of the patients using SQ sumatriptan 3 mg showed efficacy and 89% reported efficacy after 2 mg. Seventy-nine percent reported side effects after the use of SQ sumatriptan 6 mg (29% severe side effects). After the use of 2 mg SQ sumatriptan, only 50% of the patients reported side effects, none of these were classified as severe. Patients' preference was 41% for 6 mg sumatriptan, 28% for doses less than 6 mg, and 31% for oxygen. We conclude that sumatriptan in doses less than 6 mg can be effective in the acute treatment of cluster headache attacks. We suggest that patients should have experience in their individual efficacy of sumatriptan doses less than 6 mg.

A Case of Myocardial Infarction with Sumatriptan Use

Sumatriptan is widely used in the treatment of acute attacks of cluster headache. It is a serotonin-1 (5HT-1) agonist. Several studies have reported an association between sumatriptan use and myocardial infarction, possibly due to the generalized vasoconstrictive nature of this agent. We report a 16-year-old male patient presenting with acute inferior myocardial infarction after sumatriptan use without any known risk factors of coronary artery disease.

Wilfred Harris' early description of cluster headache.

Wilfred Harris was a London neurologist with a significant interest in the treatment of neuralgia. Harris' descriptions of what he called migrainous neuralgia were the first recorded of cluster headache in the English medical literature. He was probably one of the first to describe the cluster phenomenon itself and the effectiveness of ergotamine in treating acute attacks of cluster headache. His seminal contributions to the clinical and therapeutic spectrum of cluster headache are reviewed.

Hypothalamic involvement and activation in cluster headache.

Cluster headache is an episodic form of primary neurovascular headache that is both severe and relatively rare. It is characterized by episodes of headache with cranial parasympathetic activation and sympathetic impairment that come in bouts, or clusters. Its pathophysiology can be divided into understanding the attack phenotype and the biotype of the periodicity. Acute attacks of cluster headache are marked by trigeminal nerve-mediated pain and with cranial autonomic activation, trigeminal-autonomic cephalalgia; an activation that characterizes the phenotype of a group of headaches. The signature feature of cluster headache is its periodicity, the daily cycle of attacks when the patient is in an active bout, or the circumannual, or other period, cycling that distinguishes the on period from the off period. Functional brain imaging with positron emission tomography and structural imaging with voxel-based morphometry have identified an area in the posterior hypothalamic gray as key in understanding cluster headache. This area is subtly enlarged in its gray matter volume, active during an acute cluster headache but inactive when patients are challenged between bouts. Cluster headache is likely to be a form of primary neurovascular pain whose phenotypic expression relies on the trigeminal-autonomic reflex, with a biotype determined by the brain area, the posterior hypothalamus, in which the lesion seems to be located. Understanding both the phenotypic expression and the biotype will, respectively, enable better acute attack treatments and better preventative management of this horrible form of headache.

Le traitement de l’algie vasculaire de la face

Introduction. – The cluster headache (CH) is one of the most severe types of head pain. It is a typical example of a periodic disease and the International Headache Society classification recognizes two forms of this disease: episodic and chronic CH. Its prevalence is about 0.1 to 0.4% in the general population. Current knowledge and key points. – Pathophysiology: A global hypothesis is still lacking to explain the pain, the vasodilation, the autonomic features (ipsilateral lacrimation, conjunctiva injection, rhinorrhea, partial Horner syndrome, etc.) and the periodicity of the CH. Pain and vasodilation seem secondary to an activation of the trigeminal vascular system and the periodicity of the attacks is thought to be due to a dysfunction of hypothalamic biologic clock mechanisms. Treatment of acute CH attacks: The most effective agents are oxygen inhalation and subcutaneous sumatriptan, a 5HT1B and D receptor agonist which has vasoconstrictor and anti-neurogenic inflammation properties by blocking the release from the trigeminal-sensitive fibers of neuropeptides such as CGRP and substance P. With subcutaneous sumatriptan, headache relief is very rapid, within 5 to 10 min. Prophylactic treatment of CH: The number of attacks per day varies from one to three, but some patients can have four to eight per day and acute treatments fail to provide sufficient relief or give rise to side-effects. Several different regimens have been proven effective. Future prospects and projects. – Contraindications and side-effects of the drugs limit the choice of the prophylactic treatment: corticosteroids in a tapering course, verapamil and methysergide are the most useful treatments of the episodic form. Lithium carbonate is more effective for the chronic stage of CH, but side-effects are often troublesome. Numerous other medications have been used for prophylaxis: valproate, capsaicin, beta-blockers. Unfortunately, double-blind studies are often lacking and are difficult to realize due to spontaneous variable remission of episodic CH. When adequate trials of drug therapies show a total resistance to the treatments, surgery may be considered. Radiofrequency trigeminal rhizotomy is the treatment of choice with 70% of beneficial effects. Risks and complications have to be discussed in balance with the benefit of the different surgical procedures.

PET and MRA findings in cluster headache and MRA in experimental pain.

Cluster headache (CH), like migraine, is still regarded as a vascular headache although in both conditions a CNS cause has been suggested. To examine neurovascular mechanisms in CH. The authors used functional imaging with PET to investigate 18 CH patients (25 to 62 years old). Ten were in the active period (nine patients with induced attacks and one with spontaneous attack) and eight were out of their bout. In addition, the authors studied spontaneous CH and experimental pain in volunteers using MR angiography. When an acute CH attack was triggered with nitroglycerin (NTG), activation occurred in the ipsilateral posterior inferior hypothalamic gray, the contralateral ventroposterior thalamus, the anterior cingulate cortex, the ipsilateral basal ganglia, the right anterior frontal lobe, and both insulae. In patients out of the bout who experienced only a mild NTG headache, activation was seen bilaterally in the insulae and frontal cortices, the anterior cingulate cortex, the right thalamus, and the left basal ganglia, but not in the hypothalamic gray area. In addition, the authors found a significant activation (vasodilatation) in the region of the major basal arteries that was caused in part by NTG but was also observed in the spontaneous case and could be induced by capsaicin injection into the forehead. Therefore, the vasodilatation is likely to be mediated by neural mechanisms involved in the acute CH attacks that are present in every human being. Dilatation of cranial vessels is not specific to any particular headache syndrome but generic to cranial neurovascular activation, probably mediated by the trigeminoparasympathetic reflex. These data confirm that CH is a CNS disorder best considered as a form of neurovascular headache.

Studies of Platelet Monoamine Oxidase Activity during an Acute Cluster Headache Attack.

Studies of Platelet Monoamine Oxidase Activity during an Acute Cluster Headache Attack.

Early Clinical Experience with Subcutaneous GR 43 175 in Acute Cluster Headache Attacks

Early Clinical Experience with Subcutaneous GR 43 175 in Acute Cluster Headache Attacks