Occipital Nerve Stimulation for Refractory Chronic Cluster Headache: A Cost-Effectiveness Study.

INTRODUCTION: Occipital nerve stimulation (ONS) is proposed to treat refractory chronic cluster headache (rCCH), but its cost-effectiveness has not been evaluated, limiting its diffusion and reimbursement. MATERIALS AND METHODS: We performed a before-and-after economic study, from data collected prospectively in a nation-wide registry. We compared the cost-effectiveness of ONS associated with conventional treatment (intervention and postintervention period) to conventional treatment alone (preintervention period) in the same patients. The analysis was conducted on 76 rCCH patients from the French healthcare perspective at three months, then one year by extrapolation. Because of the impact of the disease on patient activity, indirect cost, such as sick leave and disability leave, was assessed second. RESULTS: The average total cost for three months was €7602 higher for the ONS strategy compared to conventional strategy with a gain of 0.07 quality-adjusted life-years (QALY), the incremental cost-effectiveness ratio (ICER) was then €109,676/QALY gained. The average extrapolated total cost for one year was €1344 lower for the ONS strategy (p = 0.5444) with a gain of 0.28 QALY (p < 0.0001), the ICER was then €-4846/QALY gained. The scatter plot of the probabilistic bootstrapping had 80% of the replications in the bottom right-hand quadrant, indicating that the ONS strategy is dominant. The average indirect cost for three months was €377 lower for the ONS strategy (p = 0.1261). DISCUSSION: This ONS cost-effectiveness study highlighted the limitations of a short-time horizon in an economic study that may lead the healthcare authorities to reject an innovative strategy, which is actually cost-effective. One-year extrapolation was the proposed solution to obtain results on which healthcare authorities can base their decisions. CONCLUSION: Considering the burden of rCCH and the efficacy and safety of ONS, the demonstration that ONS is dominant should help its diffusion, validation, and reimbursement by health authorities in this severely disabled population.

Occipital nerve stimulation improves the quality of life in medically-intractable chronic cluster headache: Results of an observational prospective study.

Background Occipital nerve stimulation (ONS) has been proposed to treat chronic medically-intractable cluster headache (iCCH) in small series of cases without evaluation of its functional and emotional impacts. Methods We report the multidimensional outcome of a large observational study of iCCH patients, treated by ONS within a nationwide multidisciplinary network ( https://clinicaltrials.gov NCT01842763), with a one-year follow-up. Prospective evaluation was performed before surgery, then three and 12 months after. Results One year after ONS, the attack frequency per week was decreased >30% in 64% and >50% in 59% of the 44 patients. Mean (Standard Deviation) weekly attack frequency decreased from 21.5 (16.3) to 10.7 (13.8) ( p = 0.0002). About 70% of the patients responded to ONS, 47.8% being excellent responders. Prophylactic treatments could be decreased in 40% of patients. Functional (HIT-6 and MIDAS scales) and emotional (HAD scale) impacts were significantly improved, as well as the health-related quality of life (EQ-5D). The mean (SD) EQ-5D visual analogic scale score increased from 35.2 (23.6) to 51.9 (25.7) ( p = 0.0037). Surgical minor complications were observed in 33% of the patients. Conclusion ONS significantly reduced the attack frequency per week, as well as the functional and emotional headache impacts in iCCH patients, and dramatically improved the health-related quality of life of responders.

Refractory chronic cluster headache: a consensus statement on clinical definition from the European Headache Federation.

Chronic cluster headache (CCH) often resists to prophylactic pharmaceutical treatments resulting in patients' life damage. In this rare but pragmatic situation escalation to invasive management is needed but framing criteria are lacking. We aimed to reach a consensus for refractory CCH definition for clinical and research use. The preparation of the final consensus followed three stages. Internal between authors, a larger between all European Headache Federation members and finally an international one among all investigators that have published clinical studies on cluster headache the last five years. Eighty-five investigators reached by email. Proposed criteria were in the format of the International Classification of Headache Disorders III-beta (description, criteria, notes, comments and references). Following this evaluation eight drafts were prepared before the final. Twenty-four (28.2%) international investigators commented during two rounds. Refractory CCH is described in the present consensus as a situation that fulfills the criteria of ICHD-3 beta for CCH with at least three severe attacks per week despite at least three consecutive trials of adequate preventive treatments. The condition is rare, but difficult to manage and invasive treatments may be needed. The consensus addresses five specific clinical and paraclinical diagnostic criteria followed by three notes and specific comments. Although refractory CCH may be not a separate identity these specific diagnostic criteria should help clinicians and investigators to improve patient's quality of life.

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.

Primary cough headache, primary exertional headache, and primary headache associated with sexual activity: a clinical and radiological study.

INTRODUCTION: The purposes of this study are to describe clinical features of primary cough headache, primary exertional headache, and primary headache associated with sexual activity and to evaluate potential association with abnormalities in the cerebral or cervical venous circulation. METHODS: This multicentre, observational, non-interventional consecutive cohort study included patients fulfilling ICHD-II criteria for primary cough headache (N = 10), primary exertional headache (N = 11), or primary headache associated with sexual activity (N = 20), as well as 16 headache-free controls. Each patient was evaluated clinically and underwent craniocervical MRV of the cranial circulation. All scans were interpreted centrally by blinded raters, using the Farb criteria proposed for idiopathic intracranial hypertension. Stenosis was defined as a Farb score <3 in left or right transverse sinuses or jugular veins. RESULTS: In all primary headache groups, headaches were most frequently diffuse, severe, or very severe. Headache duration was significantly shorter in patients with cough headache (median 6.5 versus 20 and 60 min). An exploitable magnetic resonance venogram was obtained for 36 patients. Stenosis was detected in none of the control group, but in 5/7 patients with primary cough headache group, 2/10 patients with primary exertion headache, and 12/19 patients with primary headache associated with sexual activity. The frequency of stenosis was significantly different from the control group in the primary cough headache and primary headache associated with sexual activity groups. CONCLUSIONS: Headaches provoked by cough and sexual activity are possibly associated with venous abnormalities in a significant subgroup of affected patients. As the literature shows conflicting results, this venous stenosis can be considered as a promoting factor.

Framing education on headache disorders into the Global Burden of Disease Study 2010. The European Headache Federation stands ready.

Framing education on headache disorders into the Global Burden of Disease Study 2010. The European Headache Federation stands ready.

Rizatriptan for treatment of acute migraine in patients taking topiramate for migraine prophylaxis.

OBJECTIVE: To assess efficacy and tolerability of rizatriptan orally disintegrating tablet (ODT) for treatment of acute migraine in patients using topiramate for migraine prophylaxis. BACKGROUND: There are limited data from prospective controlled trials demonstrating the benefit of triptans in patients who experience migraine attacks while taking prophylactic medication. METHODS: This was a worldwide, randomized, placebo-controlled, double-blind, multiple-attack study in adults with a >1-year history of migraine taking a stable dose of topiramate for migraine prophylaxis and experiencing ≥2 moderate/severe attacks per month. Participants treated 3 moderate/severe attacks in crossover fashion (2 with rizatriptan 10-mg ODT, 1 with placebo) following random assignment to 1 of 3 treatment sequences. The primary end point was 2-hour pain relief. RESULTS: Two-hour pain relief was significantly greater with rizatriptan compared with placebo (55.0% vs 17.4%, P < .001). Response rates also favored rizatriptan for sustained pain relief from 2-24 hours (32.6% vs 11.1%, P < .001), 2-hour pain freedom (36.0% vs 6.5%, P < .001), normal functional ability at 2 hours (42.2% vs 12.7%, P < .001), and overall treatment satisfaction at 24 hours (60.8% vs 33.6%, P < .001). Few participants reported adverse experiences (16 [15.8%] with rizatriptan, 3 [3.2%] with placebo); none were serious. CONCLUSION: Rizatriptan 10-mg ODT was superior to placebo at all pain end points for treatment of acute migraine in patients using topiramate for migraine prophylaxis. Rizatriptan was generally well tolerated in this population. These results are comparable with those from clinical trials in patients not using prophylaxis, suggesting that the use of topiramate does not affect the efficacy or tolerability of rizatriptan for acute migraine treatment.

Headaches secondary to psychiatric disorders (HSPD): a retrospective study of 87 patients.

OBJECTIVE: We describe a sample of patients receiving a diagnosis of headache attributed to psychiatric disorder (HSPD). BACKGROUND: The international literature to date provides only a few case reports of patients presenting with HSPD. METHOD: A retrospective study of the medical records of all patients having received HSPD when consulting at a headache emergency center during 2009. RESULTS: Out of a total of 8479 patients seen during one year, 25 men and 62 women received an HSPD diagnosis (1.02%), mean age 40.3 ± 14 years. The psychiatric disorders concerned were: depressive disorder (n = 37), generalized anxiety (n = 25), panic disorder (n = 5), psychotic disorder (n = 5) undifferentiated somatoform disorder (n = 4), somatization disorder (n = 1), and posttraumatic stress disorder (n = 1). Data were missing for 10 patients. Whether the headache had occurred only during the evolution of a psychiatric disorder was not recorded for any of the patients. Headache description was tension type (n = 45), atypical (n = 23), and migraine (n = 19). Half of the sample were chronic daily headaches (n = 44), but only 14.8% (n = 13) presented with medication overuse. One-fourth of the patients suffered from pain in other parts of the body (n = 21), 40% had already had complementary investigations and consultations for their headache. CONCLUSION: This study shows that in practice HSPD diagnosis is rarely used. When used, International Classification of Headache Disorders, 2nd edition criteria are not strictly applied. The criterion "headache occurring only during the evolution of the psychiatric disorder" is not checked. Not only are atypical headaches considered but, in the majority of cases, HSPD diagnosis is given with tension-type or migraine-type headache. Even though psychotic disorder and somatization disorder are the only psychiatric disorders accepted for HSPD in the classification itself (International Classification of Headache Disorders, 2nd edition code 12), in clinical practice they are not frequently involved whereas depression and generalized anxiety are. It may call for the removal of those appendix diagnoses in the classification itself.

Long-Term Efficacy of Occipital Nerve Stimulation for Medically Intractable Cluster Headache.

BACKGROUND: Occipital nerve stimulation (ONS) has been proposed to treat refractory chronic cluster headache (rCCH) but its efficacy has only been showed in small short-term series. OBJECTIVE: To evaluate ONS long-term efficacy in rCCH. METHODS: We studied 105 patients with rCCH, treated by ONS within a multicenter ONS prospective registry. Efficacy was evaluated by frequency, intensity of pain attacks, quality of life (QoL) EuroQol 5 dimensions (EQ5D), functional (Headache Impact Test-6, Migraine Disability Assessment) and emotional (Hospital Anxiety Depression Scale [HAD]) impacts, and medication consumption. RESULTS: At last follow-up (mean 43.8 mo), attack frequency was reduced >50% in 69% of the patients. Mean weekly attack frequency decreased from 22.5 at baseline to 9.9 (P < .001) after ONS. Preventive and abortive medications were significantly decreased. Functional impact, anxiety, and QoL significantly improved after ONS. In excellent responders (59% of the patients), attack frequency decreased by 80% and QoL (EQ5D visual analog scale) dramatically improved from 37.8/100 to 73.2/100. When comparing baseline and 1-yr and last follow-up outcomes, efficacy was sustained over time. In multivariable analysis, low preoperative HAD-depression score was correlated to a higher risk of ONS failure. During the follow-up, 67 patients experienced at least one complication, 29 requiring an additional surgery: infection (6%), lead migration (12%) or fracture (4.5%), hardware dysfunction (8.2%), and local pain (20%). CONCLUSION: Our results showed that long-term efficacy of ONS in CCH was maintained over time. In responders, ONS induced a major reduction of functional and emotional headache-related impacts and a dramatic improvement of QoL. These results obtained in real-life conditions support its use and dissemination in rCCH patients.

Guidelines for the organization of headache education in Europe: the headache school II.

In order to promote education on headache disorders, European Headache Federation (EHF) in conjunction with National Headache Societies organizes educational courses meeting uniform standards according to previous published guidelines. Based on six headache summer schools' experience, an EHF subcommittee has reviewed these guidelines, and here the revised version is presented. The goals remain the same: quality courses that will attract physicians and neurologists seeking to increase their knowledge, skills, and understanding in the area of primary and secondary headache. Detailed guidelines, a day-to-day program, and a multiple-choice test battery have now been outlined. It is recommended to include practical sessions with patient interviews and hands-on demonstrations of non-pharmacological treatment strategies. For countries that want a 'low cost' education program, a Video School program of a similar scientific standard has been developed. To be certified for CME credits, patronage, and financial support from EHF, it is highly recommended to adhere to the suggested teaching strategies. We hereby aim to promote and professionalize the education in headache disorders and endorse the educational courses meeting uniform standards of excellence.

Impact of a public sensitization campaign on migraine management in France.

Migraine is a common and frequently disabling condition. Nevertheless, many migraine sufferers do not consult for migraine, are not medically followed up and self-treat the attacks. "Tour de France of migraine" consisted of free-access conferences held in six large towns in France following a wide public information campaign. This sensitization campaign aimed at providing participants with educational information on migraine disease and on current therapies. Headache sufferers were then invited to respond to two consecutive questionnaires delivered at the end of the conferences and 3 months later to assess the influence of the information delivered on their migraine management. Tour de France of migraine recruited mainly severe migraine sufferers, most of whom had already consulted and were medically followed up. However, migraine management was often suboptimal in these subjects since most of them found their acute treatment of attacks ineffective and only few of them received a prophylactic treatment. Three months after the conferences, more than half of respondents had consulted for headaches. There was a significant improvement in migraine-related disability, as reflected by a significant decrease in mean Headache Impact Test 6-item score, which might have been related to the higher proportion of subjects receiving a prophylactic treatment of migraine. The Tour de France of migraine campaign revealed the difficulty in sensitizing migraine sufferers towards the necessity of being medically followed up. Mainly patients with severe migraine attended the conferences and derived clinical benefit from the educational program. Other strategies should be developed to reach a wider population of migraine sufferers.

[New horizons for acute and prophylactic treatments of migraine]. / Les avancées dans les traitements de crise et de fond de la maladie migraineuse.

The current treatment of migraine attacks is triptans and NSAIDs, but the calcitonin gene-related peptide (CGRP) has emerged as a key neuropeptide target for migraine therapy. Despite an off target class effect on liver enzymes, two CGRP receptor antagonists, ubrogepant and rimegepant, remain in development, together with a 5-HT1F receptor agonist (lasmiditan), for which cardiovascular contraindications that limit the utility of triptans do not exist. Importantly, to avoid an excessive use of acute medication with the risk of medication overuse, prophylactic therapeutics are the best choice. To date, monoclonal antibodies which block CGRP actions are on the market all over the world but not yet in France. The research is very active in different directions and targets notably hypothalamic neuropeptides because the hypothalamus hosts many key neuropeptide systems that seem to play a role in migraine physiopathology. These neuropeptides include orexins, oxytocin, neuropeptide Y (NPY) and pituitary adenylate cyclase-activating polypeptide (PACAP). In addition, other promising drugs for the treatment of migraine are nitric oxide synthase inhibitors and acid-sensing ion channel (ASIC) blockers.

The clinical and radiological spectrum of reversible cerebral vasoconstriction syndrome. A prospective series of 67 patients.

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by the association of severe headaches with or without additional neurological symptoms and a 'string and beads' appearance on cerebral arteries, which resolves spontaneously in 1-3 months. We present the clinical, neuroimaging and outcome data of 67 consecutive patients prospectively diagnosed over 3 years in our institution with an angiographically confirmed RCVS. There were 43 females and 24 males with a mean age of 42 years (19-70). RCVS was spontaneous in 37% of patients and secondary in the 63% others, to postpartum in 5 and to exposure to various vasoactive substances in 37, mainly cannabis, selective serotonin-recapture inhibitors and nasal decongestants. The main pattern of presentation (94% of patients) was multiple thunderclap headaches recurring over a mean period of 1 week. In 51 patients (76%), headaches resumed the clinical presentation. Various complications were observed, with different time courses. Cortical subarachnoid haemorrhage (cSAH) (22%), intracerebral haemorrhage (6%), seizures (3%) and reversible posterior leukoencephalopathy (9%) were early complications, occurring mainly within the first week. Ischaemic events, including TIAs (16%) and cerebral infarction (4%), occurred significantly later than haemorrhagic events, mainly during the second week. Significant sex differences were observed: women were older, had more frequent single-drug exposure and a higher rate of stroke and cSAH. Sixty-one patients were treated by nimodipine: 36% had recurrent headaches, 7% TIAs and one multiple infarcts. The different time courses of thunderclap headaches, vasoconstriction and strokes suggest that the responsible vasospastic disorder starts distally and progresses towards medium sized and large arteries. No relapse was observed during the 16 +/- 12.4 months of follow-up. Our data suggest that RCVS is more frequent than previously thought, is more often secondary particularly to vasoactive substances, and should be considered in patients with recurrent thunderclap headaches, cSAH or cryptogenic strokes with severe headaches.

[Treatments of migraine]. / Traitement de la migraine.

During the 1980s, a new class of drugs for the acute treatment of migraine attacks was developed, the triptans. These agents are selective 5-HT1B/1D serotonin receptor agonists, and were developed in order to address the underlying biological mechanism of the migraine attack. French guidelines in migraine are available since 2002. It is recommended to use a stratified treatment approach during the first consultation with the use of NSAID in first line acute treatment and triptan in second line. It is also recommended to use prophylactic treatment when the patient experience frequent and/or severe migraine attack with a bad quality of life and a real impairment.

[Prescription of aspirin in recent acute painful disorders: results of a survey among French general practitioners]. / Prescription d'aspirine dans les douleurs aiguës récentes: résultats d'une enquête en médecine générale.

AIMS: To analyse recent acute painful conditions for which general practitioners (GPs) would prescribe aspirin. METHODS: Prospective observational study investigating GPs' prescription of aspirin to adult patients with acute pain of < or =5 days of duration. Pain intensity was graded on a 100 mm visual analogue scale (VAS) prior to and at the 48th hour of aspirin therapy. RESULTS: 4765 patients (53.9% males), aged 42.6 +/- 14.7 years, with recent acute pain (2.2 +/- 1.2 days) were enrolled. Aspirin was prescribed at a mean daily dose of 3g, for musculoskeletal pain (40.8%), headaches and/or migraine (30.7%), ENT pain (23.2%) or dental pain (9.5%), some patients having complained of different types of pain. Pain relief was assessable in 3793 patients (79.6%). In this population, pain intensity was reduced by 65% within 48 hours, from 63.5 +/- 16.7 mm to 22.2 +/- 17.1 mm on the VAS. The rate of responders (decrease > or =75 % on VAS) was 39.6%; however it varied markedly across the different painful disorders. CONCLUSION: Our survey suggests that GPs may prescribe aspirin for acute pain states similar to those for which they prescribe over-the-counter non aspirin non steroidal anti-inflammatory drugs.

Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4).

Few studies have directly compared the clinical features of neuropathic and non-neuropathic pains. For this purpose, the French Neuropathic Pain Group developed a clinician-administered questionnaire named DN4 consisting of both sensory descriptors and signs related to bedside sensory examination. This questionnaire was used in a prospective study of 160 patients presenting with pain associated with a definite neurological or somatic lesion. The most common aetiologies of nervous lesions (n=89) were traumatic nerve injury, post herpetic neuralgia and post stroke pain. Non-neurological lesions (n=71) were represented by osteoarthritis, inflammatory arthropathies and mechanical low back pain. Each patient was seen independently by two experts in order to confirm the diagnosis of neuropathic or non-neuropathic pain. The prevalence of pain descriptors and sensory dysfunctions were systematically compared in the two groups of patients. The analysis of the psychometric properties of the DN4 questionnaire included: face validity, inter-rater reliability, factor analysis and logistic regression to identify the discriminant properties of items or combinations of items for the diagnosis of neuropathic pain. We found that a relatively small number of items are sufficient to discriminate neuropathic pain. The 10-item questionnaire developed in the present study constitutes a new diagnostic instrument, which might be helpful both in clinical research and daily practice.

Guidelines for the organization of headache education in Europe: the headache school.

According to its mission statement, one of the goals of the European Headache Federation (EHF) is to "educate Europe" about headache through the teaching of the key health personnel, such as young physicians and all those involved in headache management, about the seriousness of headache disorders. The countries of Europe share a close geographical proximity that facilitates international exchanges, particularly between university faculties. In recent years, this has, indeed, been the working basis of European educational endeavours in the field of headache. For a number of years, annual summer schools were organized in different European countries and a permanent Summer Headache School was set up in Cambridge (to be held every alternate year). The last summer headache school was held in Vilnius in 2002. In the past decade, a patronage scheme was also set up, which, combining two or more countries (one developed, one or more developing), allowed international exchanges of doctors and students for training purposes. In some centres, participants were also able to gain clinical practice and research experience by staying at the host institutions for extended periods of time. As a result of all this activity there have emerged, in Europe, "clusters" of people with a particular interest in headache. However, the rapid growth of insight into headache (new molecules, new headache categories, etc.) has contributed to a widening of the scientific gap between developing and developed countries. Moreover, in the past four years, due to the relative restriction of national/international drug company budgets, it has proved possible to organize only relatively inexpensive teaching courses. As a result, countries whose medical communities had been developing a "headache culture" now find themselves destined to be increasingly held back. Therefore, the EHF, in order to promote education on headache in Europe at national level, felt there was a need for guidelines for the organization of educational courses that meet uniform standards of excellence and in terms of code of conduct: guaranteed courses that will attract investors and those seeking to increase their knowledge, skills and understanding in the area of primary and secondary headache. The guidelines, presented here, specify the ideal length of a headache course, the number of lectures it should include, as well as the ideal number of participants and teachers. A sample course outline is provided, together with a checklist to help the organizers to meet the criteria for an EHF-approved headache school.

[Cluster headache treatment]. / Traitements de l'algie vasculaire de la face.

UNLABELLED: Acute treatment: sumatriptan, oxygen inhalation. Prophylactic treatment: verapamil, lithium carbonate. Transitional treatment. SURGICAL TREATMENT: deep brain stimulation, occipital nerve stimulation, stimulation of the sphenopalatin ganglion.