Chronic Chronic Cluster Headache Research Articles

CGRP-Targeted Therapy for Episodic and Chronic Cluster Headache.

Chronic cluster headache (CH) substantially affects patients' quality of life, and treatment remains challenging. The current article reviewed controlled studies for new treatment options targeting calcitonin gene-related peptide (CGRP) or its receptors in CH and discussed the current gaps and future directions for the treatment of chronic CH. Two anti-CGRP monoclonal antibodies (i.e., galcanezumab and fremanezumab) completed randomized-control trials for efficacy for the preventive treatment of episodic and chronic CH. Galcanezumab was effective for preventing episodic CH but not chronic CH. Fremanezumab was ineffective in preventing episodic and chronic CH. Studies for other anti-CGRP monoclonal antibodies and CGRP antagonists are still pending for results. There are no randomized controlled trials for CGRP-targeted therapies that showed efficacy for chronic CH prevention. The different responses to galcanezumab between episodic and chronic CH may be due to the study design, i.e., the allowance of concomitant preventive therapies in the chronic CH study but not in the episodic CH study. Another reason for the discrepancies is the different roles and sensitivity of CGRP in chronic CH.

Occipital Nerve Stimulation Tested in Medication-Refractory Chronic Cluster Headache

In chronic cluster headache (CH), as opposed to episodic CH, the attacks occur year-round. Chronic CH is also harder to treat, highlighted by recent

Long-term Outcomes of Computerized Tomography-Guided Sphenopalatine Ganglion-Targeted Pulsed Radiofrequency for Refractory Cluster Headache.

To further evaluate the efficacy and safety of computerized tomography-guided sphenopalatine ganglion-targeted pulsed radiofrequency treatment for patients with refractory episodic and chronic cluster headache (CH). Forty-five patients with refractory episodic CH and 14 patients with chronic CH who underwent computerized tomography-guided sphenopalatine ganglion-targeted pulsed radiofrequency between January 2011 and December 2018 at the Beijing Tiantan Hospital were included and analyzed in this retrospective cohort study. A total of 59 patients underwent 106 computerized tomography-guided pulsed radiofrequency procedures throughout the observational period. Effective remission was observed in 95.6% and 64.3% of patients with refractory episodic and chronic CH, respectively. Repeated computerized tomography-guided sphenopalatine ganglion-targeted pulsed radiofrequency procedures for recurrent CH was also proven to be effective. No severe side effects or complications were observed in this study. The computerized tomography-guided sphenopalatine ganglion-targeted pulsed radiofrequency procedure is an effective, safe, and repeatedly effective strategy for refractory CH. For patients who have not responded to conservative treatment, this minimally invasive intervention is a reliable alternative.

Suboccipital steroid injection alone as a preventive treatment for cluster headache

BackgroundSuboccipital steroid injection can be used as a preventive treatment for episodic and chronic cluster headache (CH). In recent studies, prophylactic treatment has been used in addition to suboccipital steroid injection. In this study, we aimed to investigate the effectivity of the sole use of rapid- and long-acting steroid injections without prophylactic treatment in patients with episodic and chronic CH. MethodsThe retrospective study included 51 patients with episodic and chronic CH that underwent greater occipital nerve (GON) blockade with a single dose of rapid- and long-acting steroid injection without additional prophylactic treatment. The frequency, severity, and duration of attacks after GON blockade as well as the side effects and long-term outcomes were reviewed. ResultsIn 28 (54.9%) patients, no attack occurred after GON blockade and cluster bouts were aborted. Mean duration of attacks was 86.67 ± 37.45 min before the treatment. However, in the 23 patients that had at least one attack after GON blockade, the mean duration of attacks was 31.73 ± 36.10 min between post-treatment days 0–3, 29.35 ± 40.49 min between post-treatment days 4–10, 28.48 ± 42.17 min between post-treatment days 11–28, and 35.65 ± 46.55 min after the post-treatment day 28 (p < 0.001). Moreover, 10 (37.04%) out of 27 patients with episodic CH who periodically had one or two cluster bouts in a year had no CH attack at the time of the expected subsequent cluster bout. ConclusionGON blockade is a practical, reliable, and cost-effective treatment option for patients with episodic and chronic CH. Moreover, GON blockade is highly effective in reducing headache attacks and even aborting cluster bouts in CH patients without requiring additional prophylactic treatment.

Deep brain stimulation in headache.

Deep brain stimulation of the posterior hypothalamic area was first introduced in 2000 to treat drug-refractory chronic cluster headache (CH). So far, hypothalamic stimulation has been employed in 79 patients suffering from various forms of intractable short-lasting unilateral headache forms, mainly trigeminal autonomic cephalalgias. The majority were (88.6%) chronic CH, including one patient who suffered from symptomatic chronic CH-like attacks; the remaining were short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT), one had paroxysmal hemicranias and one symptomatic trigeminal neuralgia. Overall, after a mean follow up of 2.2 years, 69.6% (55) hypothalamic-stimulated patients showed a ≥50% improvement. These observations need confirmation in randomised, controlled trials. A key role of the posterior hypothalamic area in the pathophysiology of unilateral short-lasting headaches, possibly by regulating the duration rather than triggering the attacks, can be hypothesised. Because of its invasiveness, hypothalamic stimulation can be proposed only after other, less-invasive, neurostimulation procedures have been tried.

Non-invasive vagus nerve stimulation for PREVention and Acute treatment of chronic cluster headache (PREVA): A randomised controlled study.

BackgroundChronic cluster headache (CH) is a debilitating disorder for which few well-controlled studies demonstrate effectiveness of available therapies. Non-invasive vagus nerve stimulation (nVNS) was examined as adjunctive prophylactic treatment of chronic CH.MethodsPREVA was a prospective, open-label, randomised study that compared adjunctive prophylactic nVNS (n = 48) with standard of care (SoC) alone (control (n = 49)). A two-week baseline phase was followed by a four-week randomised phase (SoC plus nVNS vs control) and a four-week extension phase (SoC plus nVNS). The primary end point was the reduction in the mean number of CH attacks per week. Response rate, abortive medication use and safety/tolerability were also assessed.ResultsDuring the randomised phase, individuals in the intent-to-treat population treated with SoC plus nVNS (n = 45) had a significantly greater reduction in the number of attacks per week vs controls (n = 48) (−5.9 vs −2.1, respectively) for a mean therapeutic gain of 3.9 fewer attacks per week (95% CI: 0.5, 7.2; p = 0.02). Higher ≥50% response rates were also observed with SoC plus nVNS (40% (18/45)) vs controls (8.3% (4/48); p < 0.001). No serious treatment-related adverse events occurred.ConclusionAdjunctive prophylactic nVNS is a well-tolerated novel treatment for chronic CH, offering clinical benefits beyond those with SoC.

Success, failure, and putative mechanisms in hypothalamic stimulation for drug-resistant chronic cluster headache

Drug-resistant chronic cluster headache (CH) is an unremitting illness with excruciatingly severe headaches that occur several times daily. Starting in 2000, a total of 19 patients with long-lasting chronic CH, with multiple daily attacks unresponsive to all known prophylactics, received stimulation of the posterior inferior hypothalamic area ipsilateral to the pain as treatment. We report long-term follow-up (median 8.7years, range 6–12years) in 17 patients. Long-lasting improvement occurred in 70% (12 of 17): 6 are persistently almost pain-free; another 6 no longer experience daily attacks but rather episodic CH interspersed with long-lasting remissions. In 5 of 6 almost pain-free patients, the stimulators have been off for a median of 3years (range 3–4years). Five patients did not improve: 4 had bilateral CH, and 3 developed tolerance after experiencing relief for 1–2years. Adverse events are electrode displacement (n=2), infection (electrode n=3; generator n=1), electrode malpositioning (n=1), transient nonsymptomatic third ventricle hemorrhage (n=1), persistent slight muscle weakness on one side (n=1), and seizure (n=1). This exceptionally long follow-up shows that hypothalamic stimulation for intractable chronic CH produces long-lasting improvement in many patients. Previous experience was limited to a median of 16months. Important new findings are as follows: stimulation is well tolerated for many years after implantation; after several years during which stimulation was necessary for relief, a persistent almost pain-free condition can be maintained when stimulation is off, suggesting that hypothalamic stimulation can change disease course; tolerance can occur after marked long-lasting improvement; and bilateral chronic CH seems to predict poor response to hypothalamic stimulation.

Costs of hypothalamic stimulation in chronic drug-resistant cluster headache: preliminary data

In about 20% of chronic cluster headache (CH) cases, drugs may become ineffective. Under these circumstances, steroids and triptans are frequently employed leading to fearful side effects in one and high costs in the other. The direct costs of drug-resistant chronic CH are mainly due to frequent medical consultations and frequent use of expensive drugs. In recent years, hypothalamic stimulation has been employed to treat drug-resistant chronic CH patients suffering multiple daily attacks and long-term results from different centres show a 60% overall benefit. Nine years since the introduction of this technique, we attempt a preliminary analysis of the direct costs of hypothalamic stimulation based on patients treated at our centre. We estimated the following direct costs as follows: cost of neurosurgery plus cost of equipment (electrode, connection and impulse generator = 25,000 euro), cost of hospital admissions in long-term follow-up (2,000 euro per admission), cost of single sumatriptan injection (25 euro). Number of daily sumatriptan injections in the year before and for each year after hypothalamic implantation was obtained from headache diaries. To estimate the saving due to the reduction in sumatriptan consumption following hypothalamic stimulation, we calculated the following for each year of follow-up after surgery: number of sumatriptan injections in the year before surgery minus number of sumatriptan injections in each year, updated to December 2008. In our 19 implanted patients, the costs of neurosurgery plus cost of equipment were 475,000 euro; the costs of hospital admissions during follow up were 250,000 euro. Reduction in sumatriptan consumption resulted in a total saving of 3,573,125 euro. Hence, in our 19 patients, the sumatriptan saving (3,573,125 euro) minus the direct costs due to operation and follow up hospitalisations (475,000 + 250,000) euro is equal to 2,848,125 euro. These preliminary results indicate that hypothalamic stimulation is associated with marked reduction of direct costs in the management of complete drug-resistant chronic CH.

Effect on Sleep of Posterior Hypothalamus Stimulation in Cluster Headache

To evaluate the structure and quality of sleep and the circadian rhythm of body core temperature (BcT degrees ) in patients with drug-resistant chronic cluster headache (CH) before and during deep brain stimulation (DBS) of the posterior hypothalamus. Chronic CH is a severe primary headache and frequently associated with disturbances in sleep. Posterior hypothalamus DBS is performed as an effective treatment of drug-resistant chronic CH. The effects of posterior hypothalamus DBS on sleep and the circadian rhythm of BcT degrees are unknown. Three male patients with chronic drug-resistant CH underwent 48-hour consecutive polysomnography (PSG) by means of the VITAPORT system with determination of BcT degrees by means of a rectal probe. Recordings were done before electrode implantation in the posterior hypothalamus and after optimized DBS of posterior hypothalamus. Before electrode implantation PSG showed nocturnal CH attacks, reduced sleep efficiency, fragmented sleep and increased periodic limb movements in sleep (PLMS). During DBS nocturnal CH attacks were abolished and sleep efficiency and PLMS improved. BcT degrees circadian rhythm was normal both before and during DBS. Our data show that DBS of posterior hypothalamus in drug-resistant chronic CH is effective in curtailing nocturnal CH attacks, and is associated with improved sleep structure and quality. Chronic CH displays a normal circadian rhythm of BcT degrees, unchanged during hypothalamic DBS.

Acute hypothalamic stimulation and ongoing cluster headache attacks

Long-term hypothalamic stimulation is effective in improving drug-resistant chronic cluster headache (CH). We assessed acute hypothalamic stimulation to resolve ongoing CH attacks in 16 patients implanted to prevent chronic CH, investigating 136 attacks. A pain intensity reduction of > or =50% occurred in 25 of 108 evaluable attacks (23.1%). Acute hypothalamic stimulation is not effective in resolving ongoing CH attacks, suggesting that hypothalamic stimulation acts by complex mechanisms in CH prevention.

Sphenopalatine Endoscopic Ganglion Block: A Revision of a Traditional Technique for Cluster Headache

The diagnosis of chronic cluster headache (CH), the most painful form of headache, is based on typical clinical features characterized by strictly unilateral pain with no side shift and ipsilateral oculofacial autonomic phenomena. The attacks occur several times a day for periods of 1 to 2 months in the episodic form of the disease or less frequently on a daily basis in the chronic form. The pathogenesis of CH involves the activation of parasympathetic nerve structures located within the sphenopalatine ganglion (SPG), which explains many of the associated symptoms, whereas the activation of the ipsilateral hypothalamic gray matter may explain its typical circadian and circannual periodicity. A number of surgical approaches have been tried in cases of chronic CH resistant to pharmacologic therapy, of which SPG blockade has been shown to have certain efficacy. We have adopted a new technique based on endoscopic ganglion blockade that approaches the pterigo-palatine fossa by way of the lateral nasal wall and consists of the injection of a mixture of local anesthetics and corticosteroids, which was performed in 20 selected patients with chronic CH, according to the International Headache Society criteria (18 male, 2 female; mean age 40 yr), who were selected for SPG blockade because they were totally drug resistant. The symptoms improved significantly, but always only temporarily, in 11 cases. These results should be considered rather good because, unlike other frequently used techniques, SPG blockade is not invasive and should therefore always be attempted before submitting patients to more invasive surgical approaches.

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.

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.

Cluster headache in the male: sex steroid pattern and gonadotropic response to luteinizing hormone releasing hormone.

Serum testosterone, dihydrotestosterone, delta 4-androstendione and 17 beta-estradiol, sex hormone binding globulin (SHBG) and gonadotropic response to luteinizing hormone releasing hormone (LHRH) were studied in 34 male subjects with episodic or chronic cluster headache (CH). The sex steroid free fractions and those bound to SHBG and albumin were determined by a simulatory computerized method based on the mass action law. Individual steroid values were dispersed over a wide range in CH patients. Total, free and carrier protein-bound testosterone levels were significantly diminished only in chronic CH, where luteinizing hormone (LH) peak values after intravenous administration of LHRH were also decreased. Basal and peak follicle stimulating hormone (FSH) levels were significantly increased in episodic and in chronic CH groups, in comparison to healthy controls.