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.

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.

[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.

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.

[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.

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.

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.

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.

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.

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.

Suboccipital steroid injections for transitional treatment of patients with more than two cluster headache attacks per day: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Suboccipital steroid injections can be used for preventive treatment of cluster headache but few data are available for the efficacy of this approach in clinical trials. We aimed to assess efficacy and safety of repeated suboccipital injections with cortivazol compared with placebo as add-on therapy in patients having frequent daily attacks. METHODS: In our randomised, double-blind, placebo-controlled trial at the Emergency Headache Centre in Paris, France, we enrolled adults aged 18-65 years with more than two cluster headache attacks per day. We randomly allocated patients to receive three suboccipital injections (48-72 h apart) of cortivazol 3·75 mg or placebo, as add-on treatment to oral verapamil in patients with episodic cluster headache and as add-on prophylaxis for those with chronic cluster headache, on the basis of a computer-generated list (blocks of four for each stratum). Injections were done by physicians who were aware of treatment allocation, but patients and the evaluating physician were masked to allocation. The primary outcome was reduction of the number of daily attacks to a mean of two or fewer in the 72 h period 2-4 days after the third injection. We assessed all patients who received at least one dose of study drug in the intention-to-treat analysis. This study is registered with ClinicalTrials.gov, number NCT00804895. FINDINGS: Between November, 2008, and July, 2009, we randomly allocated 43 patients (15 with chronic and 28 with episodic cluster headache) to receive cortivazol or placebo. 20 of 21 patients who received cortivazol had a mean of two or fewer daily attacks after injections compared with 12 of 22 controls (odds ratio 14·5, 95% CI 1·8-116·9; p=0·012). Patients who received cortivazol also had fewer attacks (mean 10·6, 95% CI 1·4-19·9) in the first 15 days of study than did controls (30·3, 21·4-39·3; mean difference 19·7, 6·8-32·6; p=0·004). We noted no serious adverse events, and 32 (74%) of 43 patients had other adverse events (18 of 21 patients who received cortivazol and 14 of 22 controls; p=0·162); the most common adverse events were injection-site neck pain and non-cluster headache. INTERPRETATION: Suboccipital cortivazol injections can relieve cluster headaches rapidly in patients having frequent daily attacks, irrespective of type (chronic or episodic). Safety and tolerability need to be confirmed in larger studies. FUNDING: None.

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.

Functional brain imaging of trigeminal neuralgia.

We used functional magnetic resonance imaging (fMRI) to analyze changes in brain activity associated with stimulation of the cutaneous trigger zone in patients with classic trigeminal neuralgia (CTN). Fifteen consecutive patients with CTN in the second or third division of the nerve, were included in this study. The fMRI paradigm consisted of light tactile stimuli of the trigger zone and the homologous contralateral area. Stimulation of the affected side induced pain in seven patients, but was not painful in eight patients on the day of the experiment. Painful stimuli were associated with significantly increased activity in the spinal trigeminal nucleus (SpV), thalamus, primary and secondary somatosensory cortices (S1, S2), anterior cingulate cortex (ACC), insula, premotor/motor cortex, prefrontal areas, putamen, hippocampus and brainstem. Nonpainful stimulation of the trigger zone activated all but three of these structures (SpV, brainstem and ACC). After a successful surgical treatment, activation induced by stimulation of the operated side was confined to S1 and S2. Our data demonstrate the pathological hyperexcitability of the trigeminal nociceptive system, including the second order trigeminal sensory neurons during evoked attacks of CTN. Such sensitization may depend on pain modulatory systems involving both the brainstem (i.e. periaqueductal gray and adjacent structures) and interconnected cortical structures (i.e. ACC). The fact that large portions of the classical 'pain neuromatrix' were also activated during nonpainful stimulation of the trigger zone, could reflect a state of maintained sensitization of the trigeminal nociceptive systems in CTN.

Acute headache in the emergency department.

In the acute setting, the primary objective is to decide whether the headache is primary, secondary but benign (for example a headache associated with a cold), or secondary to a potentially life-threatening cause (subarachnoid hemorrhage (SAH), bacterial meningitis, intracranial hypertension). The cornerstone of headache diagnosis is the interview with the patient, followed by a thorough physical examination. These two first clinical steps determine the need for investigation, immediate with inpatient care or on an outpatient basis, and the treatment to recommend, acutely and for future attacks in the case of primary headache. The indication for referral to a neurologist for long-term follow-up is assessed. Headaches can be separated into four groups: (1) recent onset and thunderclap; (2) recent onset with progressive installation: (3) well known to the patient and episodic (attacks with headache-free periods, as in episodic migraine or cluster headache); and (4) chronic daily headaches (more than 3 months, more than 15 days of headache per month). Headaches with a recent onset and judged unusual or worrisome by the patient (even one with frequent headaches) must raise the suspicion of a secondary cause and need to be investigated. Headaches that continue for months or years are more often primary, but secondary causes need to be ruled out in certain cases.

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.

The Emergency Headache Center at the Lariboisière Hospital: 7 years with more than 70,000 patients.

After 7 years and 70,000 patients of whom two-thirds women and one-third men, 77% aged 20-50 years, 90% residing in Paris or the suburban areas, we report our experience at the Lariboisière hospital Emergency headache Center. About two-thirds of our patients complained of primary headache, i.e., migraine, but the number of patients with secondary headache has progressively increased to account for about 17.3% of our current recruitment. Vascular headache, particularly after meningeal bleeding has been prevalent leading to an increased number of orders for laboratory and radiological investigations as well as hospitalizations.