[Complementary and supplementary procedures in the treatment of headache]. / Komplementäre und ergänzende Verfahren in der Kopfschmerztherapie.

In Germany, headache is one of the illnesses that most frequently leads to health impairments and to consultation with physicians. Even in children, headache is often associated with restricted activities of daily life. Nevertheless, the level of care for headache disorders is disproportionate to the medical needs. As a result, patients regularly use complementary and supportive therapeutic procedures. This review shows the procedures currently used for primary headache in childhood and adulthood, the methodological approaches and existing scientific evidence. The safety of the therapeutic options is also classified. These methods include physiotherapy, neural therapy, acupuncture, homeopathy, phytotherapy and the intake of dietary supplements. For children and adolescents with headaches, there are studies in the field of dietary supplements for coenzyme Q10, riboflavin, magnesium and vitamin D, which indicate specific effects in the reduction of headaches.

Therapeutic Exercise Parameters, Considerations, and Recommendations for Migraine Treatment: An International Delphi Study.

OBJECTIVE: The goal of this study was to reach consensus about the best exercise prescription parameters, the most relevant considerations, and other recommendations that could be useful for prescribing exercise to patients with migraine. METHODS: This was an international study conducted between April 9, 2022 and June 30, 2022. An expert panel of health care and exercise professionals was assembled, and a 3-round Delphi survey was performed. Consensus was reached for each item if an Aiken V Validity Index ≥ 0.7 was obtained. RESULTS: The study included 14 experts who reached consensus on 42 items by the third round. The most approved prescription parameters were 30 to 60 minutes of exercise per session, 3 days per week of moderate-intensity continuous aerobic exercise, and relaxation and breathing exercises for 5 to 20 minutes every day. When considering an exercise prescription, initial exercise supervision should progress to patient self-regulation; catastrophizing, fear-avoidance beliefs, headache-related disability, anxiety, depression, physical activity baseline level, and self-efficacy could influence the patients' exercise participation and efficacy; and gradual exposure to exercise could help improve these psychological variables and increase exercise efficacy. Yoga and concurrent exercise were also included as recommended interventions. CONCLUSION: From the experts in the study, exercise prescriptions should be adapted to patients with migraine considering different exercise modalities, such as moderate-intensity aerobic exercise, relaxation, yoga, and concurrent exercise, based on the patients' preferences and psychological considerations, level of physical activity, and possible adverse effects. IMPACT: The consensus reached by the experts can help prescribe exercise accurately to patients with migraine. Offering various exercise modalities can improve exercise participation in this population. The evaluation of the patients' psychological and physical status can also facilitate the adaptation of the exercise prescription to their abilities and diminish the risk of adverse events.

A Digital Therapeutic Allowing a Personalized Low-Glycemic Nutrition for the Prophylaxis of Migraine: Real World Data from Two Prospective Studies.

Migraine is a headache disorder associated with a high socioeconomic burden. The digital therapeutic sinCephalea provides an individualized low-glycemic diet based on continuous glucose measurement and is intended to provide a non-pharmacological migraine prophylaxis. We performed two prospective studies with migraine patients who used sinCephalea over a period of 16 weeks. The patients used a headache diary and recorded their migraine-related daily life impairments using the assessment tools HIT-6 and MIDAS for a pre versus post comparison. In addition, continuous glucose data of patients were compared to healthy controls. In both studies, patients reported a reduction of headache and migraine days as well as reductions in HIT-6 and MIDAS scores. More specifically, migraine days decreased by 2.40 days (95% CI [-3.37; -1.42]), HIT-6 improved by 3.17 points (95% CI [-4.63; -1.70]) and MIDAS by 13.45 points (95% CI [-22.01; -4.89]). Glucose data suggest that migraine patients have slightly increased mean glucose values compared to healthy controls, but drop into a glucose range that is below one's individual standard range before a migraine attack. In conclusion, sinCephalea is a non-pharmacological, digital migraine prophylaxis that induces a therapeutic effect within the range of pharmacological interventions.

Peripheral nerve stimulation registry for intractable migraine headache (RELIEF): a real-life perspective on the utility of occipital nerve stimulation for chronic migraine.

BACKGROUND: Migraine is common and ranked as the first cause of disability in people under fifty. Despite significant advances in its pharmacological treatment, it often remains intractable. Neuromodulation is one option considered in the management of those patients. OBJECTIVE: To assess the safety and efficacy of neuromodulation in the treatment of intractable chronic migraine using the Abbott occipital nerve stimulator. METHODS: Recruitment took place in 18 centres in 6 countries. Patients over the age of 18 who had failed three or more preventative drugs, had at least moderate disability based on MIDAS or HIT-6 score and were implanted with an Abbott neurostimulator were included in the study. Patients were followed up for a maximum of 24 months. Data were collected on adverse events, headache relief, headache days, quality of life, migraine disability, satisfaction and quality of life. RESULTS: One hundred twelve patients were included, 79 female and 33 male, with 45 patients reaching the maximum follow-up of 24 months. At 3 months, 33.7% were satisfied or very satisfied with the procedure with 43.0% reporting improved or greatly improved quality of life. 67.5% indicated that they would undergo the procedure again with satisfaction peaking at 9 months when 49.3% were satisfied or very satisfied with the procedure. At 24 months, 46.7% of available patients were satisfied or very satisfied with the procedure-18% of enrolled patients. The adverse events were however frequent with incidences of 37%, 47% and 31% respectively for hardware-, biological and stimulation-related side effects. CONCLUSION: Neuromodulation can be beneficial for selected patients with intractable chronic migraine although frequent complications have been consistently reported across studies. Further research focusing on development of better hardware and technique optimisation and in particular reliable randomised trials with significantly longer follow-ups are warranted in this field.

An Integrative Cognitive Behavioral Therapy Program for Adults With Migraine: A Feasibility Study.

OBJECTIVE: To present a novel cognitive behavioral therapy program that was developed exclusively for adults with migraine, and to assess the feasibility of this program. BACKGROUND: Unlike previous efforts, we combined different approaches of behavioral therapy into one program: relaxation therapy, cognitive behavioral therapy, trigger management. METHODS: The treatment program consists of 7 sessions (including psychoeducation, lifestyle counseling, coping with fear of attacks, trigger management, and stress management). The research was conducted in a single-group study with N = 9 completers (age: M = 41.6, SD = 17.6 years; N = 8 female, N = 1 male; N = 5 migraine without aura, N = 2 migraine with aura, N = 2 chronic migraine). After each of the group therapy sessions, evaluation questionnaires were filled out, and individual qualitative interviews were conducted after completion of the program. RESULTS: The treatment program was very well accepted. Every session was rated as comprehensible, and overall satisfaction with the sessions was high. Participants greatly appreciated having access to a specific treatment, exclusively addressing migraine. CONCLUSIONS: The idea of combining several approaches of behavioral therapy into a specific treatment program for migraine seems to be feasible and promising. A randomized controlled trial to determine the efficacy of our program is currently running.

Changes in medication cost observed in chronic cluster headache patients treated with sphenopalatine ganglion (SPG) stimulation: Analysis based on 1-year data from the Pathway R-1 Registry.

Background On-demand stimulation of the sphenopalatine ganglion (SPG) by means of an implantable neurostimulation system has been shown to be a safe and effective therapy for treatment-refractory cluster headache patients. Our objective was to estimate changes in cluster headache medication cost observed in SPG-treated chronic patients. Methods Detailed patient-level data of 71 chronic patients treated with the Pulsante® SPG Microstimulator System were available from the Pathway R-1 Registry through 12 months' follow-up. We used utilization data of preventive and acute medications reported at baseline, 3, 6, 9, and 12 months to estimate annualized drug costs for SPG-treated patients and compared it to baseline. Cost estimates for all drug/dosage combinations were developed based on German medication prices for 2016. Results In the base case analysis, mean annual acute and preventive medication costs decreased from €14,178 to €6924 (-€7254; -51%), and €559 to €328 (-€231; -41%), respectively, leading to total estimated annual drug cost savings of €7484, 97% of which were attributable to acute medications. Conclusions Our analysis suggests that SPG stimulation for the treatment of chronic cluster headache is associated with pronounced reductions in cluster headache medication usage that might lead to sizable annual savings in medication costs.

Long-term effectiveness of sphenopalatine ganglion stimulation for cluster headache.

Objectives The sphenopalatine ganglion (SPG) plays a pivotal role in cluster headache (CH) pathophysiology as the major efferent parasympathetic relay. We evaluated the long-term effectiveness of SPG stimulation in medically refractory, chronic CH patients. Methods Thirty-three patients were enrolled in an open-label follow-up study of the original Pathway CH-1 study, and participated through 24 months post-insertion of a microstimulator. Response to therapy was defined as acute effectiveness in ≥ 50% of attacks or a ≥ 50% reduction in attack frequency versus baseline. Results In total, 5956 attacks (180.5 ± 344.8, range 2-1581 per patient) were evaluated. At 24 months, 45% ( n = 15) of patients were acute responders. Among acute responders, a total of 4340 attacks had been treated, and in 78% of these, effective therapy was achieved using only SPG stimulation (relief from moderate or greater pain or freedom from mild pain or greater). A frequency response was observed in 33% ( n = 11) of patients with a mean reduction of attack frequency of 83% versus baseline. In total, 61% (20/33) of all patients were either acute or frequency responders or both. The majority maintained their therapeutic response through the 24-month evaluation. Conclusions In the population of disabled, medically refractory chronic CH patients treated in this study, SPG stimulation is an effective acute therapy in 45% of patients, offering sustained effectiveness over 24 months of observation. In addition, a maintained, clinically relevant reduction of attack frequency was observed in a third of patients. These long-term data provide support for the use of SPG stimulation for disabled patients and should be considered after medical treatments fail, are not tolerated or are inconvenient for the patients.

Cluster headache attack remission with sphenopalatine ganglion stimulation: experiences in chronic cluster headache patients through 24 months.

BACKGROUND: Cluster headache (CH) is a debilitating headache disorder with severe consequences for patient quality of life. On-demand neuromodulation targeting the sphenopalatine ganglion (SPG) is effective in treating the acute pain and a subgroup of patients experience a decreased frequency of CH attacks. METHODS: We monitored self-reported attack frequency, headache disability, and medication intake in 33 patients with medically refractory, chronic CH (CCH) in an open label follow-up study of the original Pathway CH-1 study. Patients were followed for at least 24 months (average 750 ± 34 days, range 699-847) after insertion of an SPG microstimulator. Remission periods (attack-free periods exceeding one month, per the ICHD 3 (beta) definition) occurring during the 24-month study period were characterized. Attack frequency, acute effectiveness, medication usage, and questionnaire data were collected at regular clinic visits. The time point "after remission" was defined as the first visit after the end of the remission period. RESULTS: Thirty percent (10/33) of enrolled patients experienced at least one period of complete attack remission. All remission periods followed the start of SPG stimulation, with the first period beginning 134 ± 86 (range 21-272) days after initiation of stimulation. On average, each patient's longest remission period lasted 149 ± 97 (range 62-322) days. The ability to treat acute attacks before and after remission was similar (37 % ± 25 % before, 49 % ± 32 % after; p = 0.2188). Post-remission headache disability (HIT-6) was significantly improved versus baseline (67.7 ± 6.0 before, 55.2 ± 11.4 after; p = 0.0118). Six of the 10 remission patients experienced clinical improvements in their preventive medication use. At 24 months post insertion headache disability improvements remained and patient satisfaction measures were positive in 100 % (10/10). CONCLUSIONS: In this population of 33 refractory CCH patients, in addition to providing the ability to treat acute attacks, neuromodulation of the SPG induced periods of remission from cluster attacks in a subset of these. Some patients experiencing remission were also able to reduce or stop their preventive medication and remissions were accompanied by an improvement in headache disability.

Cost-effectiveness analysis of non-invasive vagus nerve stimulation for the treatment of chronic cluster headache.

BACKGROUND: Cluster headache (CH) is a debilitating condition that is generally associated with substantial health care costs. Few therapies are approved for abortive or prophylactic treatment. Results from the prospective, randomised, open-label PREVA study suggested that adjunctive treatment with a novel non-invasive vagus nerve stimulation (nVNS) device led to decreased attack frequency and abortive medication use in patients with chronic CH (cCH). Herein, we evaluate whether nVNS is cost-effective compared with the current standard of care (SoC) for cCH. METHODS: A pharmacoeconomic model from the German statutory health insurance perspective was developed to estimate the 1-year cost-effectiveness of nVNS + SoC (versus SoC alone) using data from PREVA. Short-term treatment response data were taken from the clinical trial; longer-term response was modelled under scenarios of response maintenance, constant rate of response loss, and diminishing rate of response loss. Health-related quality of life was estimated by modelling EQ-5D™ data from PREVA; benefits were defined as quality-adjusted life-years (QALY). Abortive medication use data from PREVA, along with costs for the nVNS device and abortive therapies (i.e. intranasal zolmitriptan, subcutaneous sumatriptan, and inhaled oxygen), were used to assess health care costs in the German setting. RESULTS: The analysis resulted in mean expected yearly costs of €7096.69 for nVNS + SoC and €7511.35 for SoC alone and mean QALY of 0.607 for nVNS + SoC and 0.522 for SoC alone, suggesting that nVNS generates greater health benefits for lower overall cost. Abortive medication costs were 23 % lower with nVNS + SoC than with SoC alone. In the alternative scenarios (i.e. constant rate of response loss and diminishing rate of response loss), nVNS + SoC was more effective and cost saving than SoC alone. CONCLUSIONS: In all scenarios modelled from a German perspective, nVNS was cost-effective compared with current SoC, which suggests that adjunctive nVNS therapy provides economic benefits in the treatment of cCH. Notably, the current analysis included only costs associated with abortive treatments. Treatment with nVNS will likely promote further economic benefit when other potential sources of cost savings (e.g. reduced frequency of clinic visits) are considered. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT01701245 , 03OCT2012.

Integrated care for chronic migraine patients: epidemiology, burden, diagnosis and treatment options.

Migraine is a common neurological disorder, characterised by severe headaches. Epidemiological studies in the USA and Europe have identified a subgroup of migraine patients with chronic migraine. Chronic migraine is defined as ≥15 headache days per month for ≥3 months, in which ≥8 days of the month meet criteria for migraine with or without aura, or respond to treatment specifically for migraine. Chronic migraine is associated with a higher burden of disease, more severe psychiatric comorbidity, greater use of healthcare resources, and higher overall costs than episodic migraine (<15 headache days per month). There is a strong need to improve diagnosis and therapeutic treatment of chronic migraine. Primary care physicians, as well as hospital-based physicians, are integral to the identification and treatment of these patients. The latest epidemiological data, as well as treatment options for chronic migraine patients, are reviewed here.

Cost-effectiveness of stimulation of the sphenopalatine ganglion (SPG) for the treatment of chronic cluster headache: a model-based analysis based on the Pathway CH-1 study.

BACKGROUND: In the recent Pathway CH-1 study, on-demand stimulation of the sphenopalatine ganglion (SPG) by means of an implantable neurostimulation system was proven to be a safe and effective therapy for the treatment of chronic cluster headache. Our objective was to assess the cost-effectiveness of SPG stimulation in the German healthcare system when compared to medical management. METHODS: Clinical data from the Pathway CH-1 study were used as input for a model-based projection of the cost-effectiveness of SPG stimulation through 5 years. Medical management as the comparator treatment was modeled on the basis of clinical events observed during the baseline period of CH-1. The costs of treatment were derived from a previously published cluster headache costing study and 2014 medication, neurostimulator, and procedure costs. We computed the 5-year incremental cost-effectiveness ratio (ICER) in euros per quality-adjusted life year (QALY), with costs and effects discounted at 3 % per year. RESULTS: SPG stimulation was projected to add 0.325 QALYs over the study period, while adding €889 in cost, resulting in a 5-year ICER of €2,736 per QALY gained. Longer follow-up periods, higher baseline attack frequency, and higher utilization of attack-aborting medications led to overall cost savings. SPG stimulation was found either cost-effective or cost-saving across all scenarios investigated in sensitivity analyses. CONCLUSIONS: Our model-based analysis suggests that SPG stimulation for the treatment of chronic cluster headache, under the assumption of sustained therapy effectiveness, leads to meaningful gains in health-related quality of life and is a cost-effective treatment strategy in the German healthcare system.

Improvement of migraine symptoms with a proprietary supplement containing riboflavin, magnesium and Q10: a randomized, placebo-controlled, double-blind, multicenter trial.

BACKGROUND: Non-medical, non-pharmacological and pharmacological treatments are recommended for the prevention of migraine. The purpose of this randomized double-blind placebo controlled, multicenter trial was to evaluate the efficacy of a proprietary nutritional supplement containing a fixed combination of magnesium, riboflavin and Q10 as prophylactic treatment for migraine. METHODS: 130 adult migraineurs (age 18 - 65 years) with ≥ three migraine attacks per month were randomized into two treatment groups: dietary supplementation or placebo in a double-blind fashion. The treatment period was 3 months following a 4 week baseline period without prophylactic treatment. Patients were assessed before randomization and at the end of the 3-month-treatment-phase for days with migraine, migraine pain, burden of disease (HIT-6) and subjective evaluation of efficacy. RESULTS: Migraine days per month declined from 6.2 days during the baseline period to 4.4 days at the end of the treatment with the supplement and from 6.2.days to 5.2 days in the placebo group (p = 0.23 compared to placebo). The intensity of migraine pain was significantly reduced in the supplement group compared to placebo (p = 0.03). The sum score of the HIT-6 questionnaire was reduced by 4.8 points from 61.9 to 57.1 compared to 2 points in the placebo-group (p = 0.01). The evaluation of efficacy by the patient was better in the supplementation group compared to placebo (p = 0.01). CONCLUSIONS: Treatment with a proprietary supplement containing magnesium, riboflavin and Q10 (Migravent® in Germany, Dolovent® in USA) had an impact on migraine frequency which showed a trend towards statistical significance. Migraine symptoms and burden of disease, however, were statistically significantly reduced compared to placebo in patients with migraine attacks.

Occipital nerve stimulation for intractable chronic cluster headache or migraine: a critical analysis of direct treatment costs and complications.

BACKGROUND: Occipital nerve stimulation (ONS) has been shown to be effective for selected patients with intractable headache disorders. We performed a prospective critical evaluation of complications and direct treatment costs. METHODS: Twenty-seven patients with chronic cluster headache (CCH, N = 24) or chronic migraine (CM, N = 3) underwent a trial phase with bilateral ONS and subsequent implantation of a permanent generator (IPG), if responsive to treatment according to predefined criteria. Procedural and long-term complications as well as direct treatment costs of neuromodulation therapy of ONS were recorded over a mean follow-up period of 20 months (range 5-47 months). RESULTS: Twenty-five of 27 patients (93%) responded to treatment. Twenty-one complications in 14 patients were identified, necessitating reoperation in 13 cases. Overall treatment costs were €761,043, including hardware-related costs of €506,019, costs for primary hospital care of €210,496, and complications related to hospitalization costs of €44,528. This results in a per case-based cost of €9445 for hospitalization and €18,741 for hardware costs, totaling €28,186. CONCLUSION: ONS for treatment of refractory CCH and CM is a cost-intensive treatment option with a significant complication rate. Nevertheless, patients with refractory primary headache disorders may experience substantial relief of pain attacks, and headache days, respectively.

Stimulation of the greater occipital nerve: anatomical considerations and clinical implications.

BACKGROUND: Stimulation of the greater occipital nerve has been employed for various intractable headache conditions for more than a decade. Still, prospective studies that correlate stimulation of the greater occipital nerve with outcome of patients with respect to alleviation of headache are sparsely found in literature. OBJECTIVE: To identify anatomical landmarks for a reproducible stimulation of the greater occipital nerve. For the clinical implication, the individual response to therapy of patients with refractory chronic cluster headache undergoing occipital nerve stimulation was correlated with the postoperative localization of the electrodes and with the distribution of the stimulation field. STUDY DESIGN: Prospective observational study, approved by the local research ethics board (09-4143). SETTING: University hospital, departments of neurosurgery and neurology, institute of anatomy and radiology. METHODS: Ten formaldehyde fixed human cadavers were dissected to identify the passage of the greater occipital nerve through the trapezius muscle. The distance to the external occipital protuberance was triangulated measuring the distance of the nerve from the nuchal midline and the protuberance. Between December 2008 and December 2011, 21 consecutive patients suffering from chronic cluster headache underwent surgery in terms of bilateral occipital nerve stimulation, with electrodes placed horizontally at the level of C1. The postoperative x-rays were compared with the acquired landmarks from the anatomical study. The distribution of the stimulation field was correlated to the individual response of each patient to the therapy and prospectively analyzed with regard to reduction of daily cluster attacks and relief of pain intensity at 3 months and at last follow-up. RESULTS: The greater occipital nerve crosses the trapezius muscle at a mean distance of 31 mm below the occipital external protuberance and 14 mm lateral to the midline as found in the anatomical subjects. The electrodes were targeted at this level in all of our patients and stimulated the greater occipital nerve in all patients. Eighteen of the patients (85.7%) reported a significant reduction of the frequency of their cluster attacks and/or declined intensity of pain during the attacks. Yet, 3 of 21 patients (14.3%) did not benefit from the stimulation despite an adequate spread of the stimulation over the occiput. The spread of the stimulation-induced paraesthesias over the occiput was not correlated to a reduction of cluster attacks, to the intensity of attacks, or to the response to treatment at all. LIMITATIONS: Single center non-randomized non-blinded study. CONCLUSIONS: From our study we conclude that a reproducible stimulation of the greater occipital nerve can be achieved by placing the electrodes parallel to the atlas, at about 30 mm distance to the external occipital protuberance. The response to the stimulation is not correlated to the field width of the paraesthesia. We, therefore, consider stimulation of the main trunk of the greater occipital nerve to be more important than a large field of stimulation on the occiput. Still, an individual response to the occipital nerve stimulation cannot be predicted even by optimal electrode placement.

Stimulation of the sphenopalatine ganglion (SPG) for cluster headache treatment. Pathway CH-1: a randomized, sham-controlled study.

BACKGROUND: The pain and autonomic symptoms of cluster headache (CH) result from activation of the trigeminal parasympathetic reflex, mediated through the sphenopalatine ganglion (SPG). We investigated the safety and efficacy of on-demand SPG stimulation for chronic CH (CCH). METHODS: A multicenter, multiple CH attack study of an implantable on-demand SPG neurostimulator was conducted in patients suffering from refractory CCH. Each CH attack was randomly treated with full, sub-perception, or sham stimulation. Pain relief at 15 minutes following SPG stimulation and device- or procedure-related serious adverse events (SAEs) were evaluated. FINDINGS: Thirty-two patients were enrolled and 28 completed the randomized experimental period. Pain relief was achieved in 67.1% of full stimulation-treated attacks compared to 7.4% of sham-treated and 7.3% of sub-perception-treated attacks ( P < 0.0001). Nineteen of 28 (68%) patients experienced a clinically significant improvement: seven (25%) achieved pain relief in ≥50% of treated attacks, 10 (36%), a ≥50% reduction in attack frequency, and two (7%), both. Five SAEs occurred and most patients (81%) experienced transient, mild/moderate loss of sensation within distinct maxillary nerve regions; 65% of events resolved within three months. INTERPRETATION: On-demand SPG stimulation using the ATI Neurostimulation System is an effective novel therapy for CCH sufferers, with dual beneficial effects, acute pain relief and observed attack prevention, and has an acceptable safety profile compared to similar surgical procedures.

Headache in children: update on complementary treatments.

Complementary and alternative medicine (CAM) is widely used by both physicians and patients with primary headache syndromes. Despite a considerable number of articles addressing CAM in primary headache syndromes, the overall evidence for CAM is still poor. The aim of this review was to give an overview of the current evidence of the main alternative therapies used in the treatment of primary headache syndromes of childhood. MEDLINE and Cochrane Library were systematically searched for articles dealing with complementary and alternative treatment or prophylaxis of headache and migraine published within the past 20 years.

Grey matter changes associated with medication-overuse headache: correlations with disease related disability and anxiety.

OBJECTIVES: Medication-overuse headache (MOH) is associated with psychiatric comorbidities. Neurobiological similarities to substance dependence have been suggested. This study investigated grey matter changes, focussing on pain and reward systems. METHODS: Using voxel-based morphometry, structural MRIs were compared between 29 patients with both, MOH and migraine, according to International Headache Society criteria, and healthy controls. The Migraine Disability Assessment (MIDAS) score was used. Anxiety and depression were screened for with the Hospital Anxiety and Depression Scale (HADS) and confirmed by a psychiatrist, using the Mini International Neuropsychiatric Interview. RESULTS: Nineteen patients (66%) had a present or past psychiatric disorder, mainly affective (N = 11) and anxiety disorders (N = 8). In all patients a significant increase of grey matter volume (GMV) was found in the periaqueductal grey matter of the midbrain, which correlated positively with the MIDAS and the HADS-anxiety subscale. A GMV increase was found bilaterally in the thalamus, and the ventral striatum. A significant GMV decrease was detected in frontal regions including orbitofrontal cortex, anterior cingulate cortex, the left and right insula, and the precuneus. CONCLUSION: These findings are consistent with dysfunction of antinociceptive systems in MOH, which is influenced by anxiety. Dysfunction of the reward system may be a neurobiological basis for dependence in a subgroup of MOH patients.

Aggressiveness in different presentations of cluster headache: results from a controlled multicentric study.

BACKGROUND: The hypothalamus has been discussed as a pivotal structure for both cluster headache (CH) and aggressiveness, but little is known about the extent of self-reported aggressiveness in patients with CH. PATIENTS AND METHODS: Twenty-six patients with chronic, 25 with active episodic and 22 with episodic CH outside the active period were examined interictally with a validated questionnaire quantifying factors of aggression and compared with 24 migraine patients and 31 headache-free volunteers. RESULTS: The ANOVA was significant for the subscale 'self-aggression/depression' (F(4, 123) = 5.771, p < 0.001) with significant differences between chronic and episodic CH and healthy volunteers. No significant changes were found for other subscales and the sum scale (F(4, 123) < 1.421, p > 0.230). Especially in the clinically most affected group of patients (chronic CH and active episodic CH), high levels of "self-aggression/depression" correlate with higher prevalence of depressive symptoms and higher impairment measured on an emotional and functional level. DISCUSSION: Self-aggressive and depressive cognitions with highest scores in chronic CH seem to be reactive as they correlate with depressive symptoms and impairment. They should be considered as an important therapeutic target since they impair the patient's life significantly.

Aerobic endurance training versus relaxation training in patients with migraine (ARMIG): study protocol for a randomized controlled trial.

BACKGROUND: Migraine is one of the most frequent headache diseases and impairs patients' quality of life. Up to now, many randomized studies reported efficacy of prophylactic therapy with medications such as beta-blockers or anti-epileptic drugs. Non-medical treatment, like aerobic endurance training, is considered to be an encouraging alternative in migraine prophylaxis. However, there is still a lack of prospective, high-quality randomized trials. We therefore designed a randomized controlled trial to evaluate the efficacy of aerobic endurance training versus relaxation training in patients with migraine (ARMIG). METHODS: This is a single-center, open-label, prospective, randomized trial. Sixty participants with migraine are randomly allocated to either endurance training or a relaxation group. After baseline headache diary documentation over at least 4 weeks, participants in the exercise group will start moderate aerobic endurance training under a sport therapist's supervision at least 3 times a week over a 12-week period. The second group will perform Jacobson's progressive muscle relaxation training guided by a trained relaxation therapist, also at least 3 times a week over a 12-week period. Both study arms will train in groups of up to 10 participants. More frequent individual training is possible. The follow-up period will be 12 weeks after the training period. The general state of health, possible state of anxiety or depression, impairments due to the headache disorder, pain-related disabilities, the headache-specific locus of control, and the motor fitness status are measured with standardized questionnaires. DISCUSSION: The study design is adequate to generate meaningful results. The trial will be helpful in gaining important data on exercise training for non-medical migraine prophylaxis. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov: NCT01407861.

Evaluating integrated headache care: a one-year follow-up observational study in patients treated at the Essen headache centre.

BACKGROUND: Outpatient integrated headache care was established in 2005 at the Essen Headache Centre in Germany. This paper reports outcome data for this approach. METHODS: Patients were seen by a neurologist for headache diagnosis and recommendation for drug treatment. Depending on clinical needs, patients were seen by a psychologist and/or physical therapist. A 5-day headache-specific multidisciplinary treatment programme (MTP) was provided for patients with frequent or chronic migraine, tension type headache (TTH) and medication overuse headache (MOH). Subsequent outpatient treatment was provided by neurologists in private practice. RESULTS: Follow-up data on headache frequency and burden of disease were prospectively obtained in 841 patients (mean age 41.5 years) after 3, 6 and 12 months. At baseline mean headache frequency was 18.1 (SD = 1.6) days per month, compared to measurement at 1 year follow-up a mean reduction of 5.8 (SD = 11.9) headache days per month was observed in 486 patients (57.8%) after one year (TTH patients mean: -8.5 days per month; migraine mean: -3.2 days per month, patients with migraine and TTH mean: -5.9 days per month). A reduction in headache days ≥ 50% was observed in 306 patients (36.4%) independent of diagnosis, while headache frequency remains unchanged in 20.9% and increase in 21.3% of the patient. CONCLUSION: Multidisciplinary outpatient headache centres offer an effective way to establish a three-tier treatment offer for difficult headache patients depending on clinical needs.