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Trigeminal neuralgia is a severe facial pain disorder that is difficult to treat. Erenumab, a monoclonal antibody against the calcitonin gene-related peptide (CGRP) receptor, has proven efficacy in migraine. Erenumab modulates sensory processing in peripheral trigeminal pain pathways in mice and was reported to be effective for patients with trigeminal neuralgia in open-label studies. We aimed to evaluate the efficacy of erenumab in patients with trigeminal neuralgia.We did a randomised, double-blind, placebo-controlled trial in adults (aged 18-85 years) with idiopathic or classic trigeminal neuralgia as defined by the 3rd edition of the International Classification of Headache Disorders. The trial was based at the Danish Headache Center, Copenhagen University Hospital. Eligible participants had no clinically significant cerebrovascular or cardiovascular disease, had self-reported pain intensity of at least 4 on the 11-point Numeric Rating Scale (0=no pain, 10=worst pain imaginable), and had at least three daily pain paroxysms. After a 1-week pre-screening period, patients entered a 4-week baseline period. Participants who met pain inclusion criteria at the end of the baseline period were randomly assigned (1:1) to receive subcutaneous injections of either erenumab 140 mg or placebo and entered the 4-week follow-up period. Randomisation was done in blocks of 10 using a computer-generated schedule by a third-party company. Participants and assessors were masked to treatment allocation, and erenumab and placebo were packed in identical prefilled syringes. The primary outcome was the number of responders, defined as patients who had a reduction of at least 30% in mean average daily pain intensity during the follow-up period compared with during the baseline period, analysed in the intention-to-treat population. This trial is registered with the European Union Drug Regulating Authorities Clinical Trials Database, EudraCT number 2019-000848-95.We assessed 860 patients for suitability and excluded 741 between Oct 28, 2019, and Sept 13, 2021. 119 participants entered a 1-week pre-screening period and 26 were excluded, 93 participants entered a 4-week baseline period with 13 excluded before randomisation, and 80 participants were randomly assigned to erenumab 140 mg (n=40) or placebo (n=40). There was no difference between groups in the number of responders at 4 weeks in the intention-to-treat population (14 [35%] of 40 with erenumab vs 18 [45%] of 40 with placebo; estimated effect size -10% [95% CI -31 to 11]; p=0·36). 20 (50%) of 40 participants reported adverse events in each group. The most common adverse events were constipation (28%) and headache (10%) in the erenumab group, and headache (13%), constipation (10%), and abdominal pain (10%) in the placebo group.Erenumab did not reduce pain intensity compared with placebo in patients with trigeminal neuralgia and CGRP probably does not have an important role in paroxysmal pain. Well tolerated, effective treatments in trigeminal neuralgia are still needed.Novartis.

Objective: We investigated whether telephone follow-up consultations could lead to appropriate adjustment of treatments and a higher degree of patient satisfaction among patients with migraine and tension-type headache (TTH). Background: Migraine and TTH are disabling headache forms requiring optimized treatment. Methods: In a prospective, non-randomized, quality control study with controls comparing telephone-interview intervention (TeII) with business-as-usual (BAU) treatment, we included newly referred patients with migraine and/or TTH. The TeII group was contacted by telephone by healthcare professionals at 8 and 16 weeks after the first visit addressing headache treatment. Electronic questionnaires were sent to all participants before the first visit and after 6 months. Predefined outcomes were number of patients with change in preventive and acute medication; change in headache frequency; migraine frequency; scores from the eight-item Headache Under-Response to Treatment (HURT-8) questionnaire, Insomnia Severity Index (ISI), and Hospital Anxiety and Depression Scale (HADS); and patient satisfaction after 6 months. Results: From May 2020 to April 2021, there were 230 patients enrolled in the TeII program, whereof 96 patients were included in the analysis. For the BAU group, 91 patients with similar sex and age distribution were identified via medical-record reviews in the same period. More patients in the TeII group than in the BAU group had a change in acute medication (27/96 [28%] vs. five of 91 [6%], p < 0.001) and preventive medication (28/96 [29%] vs. 12/91 [13%], p = 0.006). Headache days per month decreased in the TeII group (−4.6, 95% confidence interval [CI] −6.5 to −2.7; p = 0.001) and the BAU group (−2.5, 95% CI −4.6 to −0.4; p = 0.018), without significant difference between the groups (p = 0.080). There was no difference in migraine frequency between the groups (TeII: 1.0 day, 95% CI, −1.3 to 1.0; BAU: 1.0 day, 95% CI, −2.5 to 0.5; p = 0.718) or HURT-8 score (TeII: 10.5, 95% CI 9.5–11.5; BAU: 13.0, 95% CI 11.7–14.2; p = 0.053). There were no changes in the ISI score (TeII: 1.0, interquartile range [IQR] 6; p = 0.152; BAU: 0.5, IQR 4.5; p = 0.824), HADS-Anxiety score (TeII: −5, IQR 5.3; p = 0.186; BAU: 1.0, IQR 4.0; p = 0.445), or HADS-Depression score (TeII: 0.0, IQR 3.0; p = 0.163; BAU: 0.0, IQR 2.0; p = 0.303) in any of the groups. There was a higher degree of patient satisfaction in the TeII group compared with the BAU group in treatment (median [IQR] score 4 [3–5] vs. 3 [3–4], p < 0.001), headache improvement (median [IQR] 3 [2–4] vs. 2 [1–3], p = 0.002), the headache program (median [IQR] 4 [3–5] vs. 3 [3–4], p < 0.001), and information (median [IQR] 4 [3–5] vs. 3 [3–4], p = 0.005). Conclusion: Patients with migraine and/or TTH benefit from a telephone follow-up approach within the first 6 months of their treatment course in terms of more efficient treatment and higher patient satisfaction.

Introduction Intravenous fosphenytoin is widely used for acute exacerbation of trigeminal neuralgia, however, few studies have investigated this treatment. We aimed to examine the efficacy and side effects of initial intravenous fosphenytoin plus oral tapering of phenytoin for exacerbation of trigeminal neuralgia. Methods Consecutive patients with primary trigeminal neuralgia were included in this prospective observational 90-days follow-up study. Data were collected using standardized interviews before, at 24 hours, day 7, 30 and 90 post loading dose. The primary outcome was the proportion of responders defined as a 50% reduction in pain intensity 24 hours post loading dose. Results We included 15 patients. Nine patients (60%) were responders. Pain intensity 24 hours post loading dose was reduced by 5.00 points on the numerical rating scale (p Conclusion Intravenous fosphenytoin relieves trigeminal neuralgia pain in most patients and provides a window for titrating prophylactic trigeminal neuralgia medications or planning neurosurgery. The decision to administer intravenous fosphenytoin should be taken with support from trigeminal neuralgia experts and involves considerations of co-morbidities and other treatment options for acute exacerbation of trigeminal neuralgia. Clinical Trial: Preregistered (ClinicalTrials.gov Identifier: NCT03712254

Background A previous European Headache Federation (EHF) guideline addressed the use of monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway to prevent migraine. Since then, randomized controlled trials (RCTs) and real-world evidence have expanded the evidence and knowledge for those treatments. Therefore, the EHF panel decided to provide an updated guideline on the use of those treatments. Methods The guideline was developed following the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. The working group identified relevant questions, performed a systematic review and an analysis of the literature, assessed the quality of the available evidence, and wrote recommendations. Where the GRADE approach was not applicable, expert opinion was provided. Results We found moderate to high quality of evidence to recommend eptinezumab, erenumab, fremanezumab, and galcanezumab in individuals with episodic and chronic migraine. For several important clinical questions, we found not enough evidence to provide evidence-based recommendations and guidance relied on experts’ opinion. Nevertheless, we provided updated suggestions regarding the long-term management of those treatments and their place with respect to the other migraine preventatives. Conclusion Monoclonal antibodies targeting the CGRP pathway are recommended for migraine prevention as they are effective and safe also in the long-term.

Introduction Medical treatments for trigeminal neuralgia secondary to multiple sclerosis have low efficacy and tolerability and scientific evidence regarding efficacy of neurosurgery is scarce. We aimed to assess neurosurgical outcome and complications in trigeminal neuralgia secondary to multiple sclerosis. Methods Patients with trigeminal neuralgia secondary to multiple sclerosis who underwent microvascular decompression, glycerol rhizolysis or balloon compression were prospectively and consecutively included from 2012 to 2019. Preoperatively, we systematically obtained clinical characteristics and performed a 3.0 Tesla MRI. Follow-up at three, six and 12 months was performed by independent assessors. Results We included 18 patients. Of the seven patients treated with microvascular decompression, two patients (29%) had an excellent outcome (both had neurovascular contact with morphological changes), three patients (43%) had a good outcome, one patient (14%) had treatment failure and one patient (14%) had a fatal outcome. Three patients (43%) had major complications. Of 11 patients treated with percutaneous procedures, seven patients (64%) had an excellent or good outcome with major complications in three patients (27%). Conclusion Percutaneous procedures provided acceptable outcome and complication rates and should be offered to the majority of patients with trigeminal neuralgia secondary to multiple sclerosis who need surgery. Microvascular decompression is less effective and has a higher complication rate in trigeminal neuralgia secondary to multiple sclerosis compared to microvascular decompression in classical and idiopathic trigeminal neuralgia. Microvascular decompression should only be considered in patients with trigeminal neuralgia secondary to multiple sclerosis when they have neurovascular contact with morphological changes.

Objectives To investigate previous treatment and clinical characteristics in migraine and tension-type headache patients at their first visit to a tertiary headache center. Methods This was a cross-sectional study using data obtained from electronic questionnaires and medical charts. Migraine and tension-type headache patients were investigated at their first visit to the Danish Headache Center. Results Out of 382 patients the main diagnoses of primary headaches were: 36% with episodic migraine, 43% with chronic migraine, 3% with episodic tension-type headache and 17% with chronic tension-type headache. The majority had attempted non-pharmacological treatment options such as physiotherapy (episodic migraine: 53%, chronic migraine: 68%, episodic tension-type headache: 50%, chronic tension-type headache: 65%) and acupuncture: (episodic migraine: 45%, chronic migraine: 62%, episodic tension-type headache: 17%, chronic tension-type headache: 51%). The majority of migraine patients had tried no more than one triptan (episodic migraine: 71%, chronic migraine: 66%). In total, 35% of episodic migraine and 19% of chronic migraine patients as well as 50% of episodic tension-type headache and 41% of chronic tension-type headache patients had never tried preventive medication. The headache under-response to treatment (HURT) questionnaire score was higher in chronic migraine (score 15) and chronic tension-type headache (score 16) patients than the episodic forms ( P Conclusions Headache patients had attempted several non-pharmacological treatments prior to their first visit at a tertiary headache center in Denmark. The limited use of acute and preventive treatment before the first visit demonstrates a need for better treatment at the primary and secondary care level.

Background Clinical trials have shown that erenumab is effective and well-tolerated for the preventive treatment of chronic migraine. To extend the results from clinical trials, we assessed the real-world efficacy and safety of erenumab in patients with chronic migraine from the outpatient clinic at the Danish Headache Center. Methods A 52-week, single-center, prospective, observation study of erenumab in adults with chronic migraine who are eligible for treatment with monoclonal antibodies against CGRP or its receptor in Denmark. The primary outcome was defined as proportion of patients who achieved ≥ 30% reduction in monthly migraine days (MMDs) from baseline to weeks 9–12. Results A total of 300 adult patients with chronic migraine were enrolled and received at least one dose of erenumab. At baseline, the mean (SD) number of monthly headache days was 23 ± 4.9 and mean number of MMDs was 16.8 ± 6.4. Of 300 enrolled patients, 273 (91.0%) patients completed 12 weeks of treatment, and 119 (39.7%) completed 52 weeks of treatment. The number of patients who achieved ≥ 30% reduction in MMDs from baseline to weeks 9–12 was 195 (71.4%) of 273 patients. Sustained ≥ 30% reduction in MMDs at all assessment periods throughout the 52-week treatment period was achieved by 102 (34%) of 300 patients. Adverse events occurred in 220 (73.3%) out of 300 patients. The most common adverse event was constipation. Treatment discontinuation due to lack of tolerability occurred in 41 (13.7%) patients. Conclusions Among adult patients with chronic migraine and previous failure of medications for migraine prevention, erenumab was found to be effective and well-tolerated.

Objectives Tension-type headache (TTH) is the most prevalent primary headache disorder. We assessed the cross-sectional impact of TTH on health related quality of life (HRQoL) in a general population. We also examined the association of HRQoL scores with headache frequency, disability, medication overuse, poor self-rated health, psychiatric comorbidity, and pain sensitivity in individuals with TTH. Methods A sample of 547 subjects completed a headache diagnostic interview, the SF-12 to calculate physical (PCS) and mental (MCS) health component scores, depression (major depression inventory [MDI]) and neuroticism (Eysenck Personality Questionnaire) measures. We defined the following headache diagnosis categories: pure TTH, pure migraine, and coexistent headache (TTH + migraine). Cases were further classified into chronic (≥15) or episodic ( Results Using generalized linear models (GLM) adjusted for age, sex and education, both PCS-12 and MCS-12 scores varied in groups distinguished by migraine and TTH status; scores were lower for individuals with coexistent headache (TTH + migraine; n=83), followed by pure TTH (n=97) and pure migraine (n=43) compared to the no headache group (n=324) (p≤0.001). In analyses considering chronicity, PCS-12 scores were lower in chronic coexistent headache followed by pure chronic TTH (CTTH), episodic migraine +/− episodic TTH (ETTH) and pure ETTH than in the no headache group (p≤0.001). MCS-12 scores were lower in pure CTTH, followed by chronic coexistent headache, episodic migraine +/− ETTH and pure ETTH compared to the no headache group (p≤0.001). Multiple regression models showed that in TTH, lower PCS-12 scores were associated with age (p=0.04), female sex (p=0.02), and poor self-rated health (p≤0.001). Lower MCS-12 scores in TTH were associated with depression (p≤0.001). Conclusions In a population sample, TTH, and to higher degree CTTH, are associated with decreased HRQoL.

Introduction A demyelinating plaque and neurovascular contact with morphological changes have both been suggested to contribute to the etiology of trigeminal neuralgia secondary to multiple sclerosis (TN-MS). The aim of this study was to confirm or refute whether neurovascular contact with morphological changes is involved in the etiology of TN-MS. Methods We prospectively enrolled consecutive TN-MS patients from the Danish Headache Center. Clinical characteristics were collected systematically. MRI scans were done using a 3.0 Tesla imager and were evaluated by the same experienced blinded neuroradiologist. Results Sixty-three patients were included. Fifty-four patients were included in the MRI analysis. There was a low prevalence of neurovascular contact with morphological changes on both the symptomatic side (6 (14%)) and the asymptomatic side (4 (9%)), p = 0.157. Demyelinating brainstem plaques along the trigeminal afferents were more prevalent on the symptomatic side compared to the asymptomatic side (31 (58%) vs. 12 (22%), p Conclusion The primary cause of TN-MS is demyelination along the intrapontine trigeminal afferents. As opposed to classical trigeminal neuralgia, neurovascular contact does not play a role in the etiology of TN-MS. Microvascular decompression should generally not be offered to patients with TN-MS. The study was registered at ClinicalTrials.gov (number NCT04371575)

Objectives We aimed to investigate whether coexistent self-reported neck pain influences cephalic and extracephalic pain sensitivity in individuals with migraine and tension-type headache (TTH) in relation to diagnosis and headache frequency. Methods A population of 496 individuals completed a headache interview based on ICHD criteria, providing data collected by self-administered questionnaires, assessments of pericranial total tenderness score (TTS) and pressure pain thresholds (PPT). Stimulus-response (SR) functions for pressure vs. pain were recorded. Presence of neck pain in the past year was assessed by the self-administered questionnaire. We categorized participants by primary headache type. We also categorized participants into 3 groups by headache frequency: chronic (≥15) or episodic ( Results Individuals with chronic followed by episodic headache had higher TTS than controls (overall p≤0.001). The difference between chronic and episodic headache subgroups was significant in the group with neck pain (p≤0.001) but not in the group without neck pain. In individuals with neck pain, mean TTS was higher in coexistent headache (migraine and TTH), 23.2 ± 10.7, and pure TTH, 17.8 ± 10.3, compared to pure migraine, 15.9 ± 10.9 and no headache 11.0 ± 8.3 (overall p Conclusions Coexistent neck pain is associated with greater pericranial tenderness in individuals with chronic headache and to a lesser degree in those with episodic headache. Sensitization may be a substrate or consequence of neck pain and primary headache, but a longitudinal study would be needed for further clarification.

BACKGROUND Combined withdrawal and early preventive medication was the most effective treatment for medication overuse headache (MOH) within the first 6 months in a previous study, but results from a longer follow-up period are lacking. OBJECTIVE (1) To measure the efficacy at 1 year of three different treatment approaches to MOH; (2) to compare withdrawal and early preventives (W+P), preventives with potential withdrawal therapy after 6 months (P+pW), and withdrawal with delayed potential preventives (W+pP); and (3) to identify predictors of chronic headache after 1 year. METHODS Patients with MOH and migraine and/or tension-type headache were randomly assigned to one of the three outpatient treatments. Headache calendar and questionnaires were filled out. Primary outcome was a reduction in headache days/month after 1 year. RESULTS Of 120 patients, 96 completed 1-year follow-up, and all were included in our analyses. Overall headache days/month were reduced from 24.6 (23.4-25.8) to 15.0 (13.0-17.0) (p

Headache and facial pain are among the most common, disabling and costly diseases in Europe, which demands for high quality health care on all levels within the health system. The role of the Danish Headache Society is to educate and advocate for the needs of patients with headache and facial pain. Therefore, the Danish Headache Society has launched a third version of the guideline for the diagnosis, organization and treatment of the most common types of headaches and facial pain in Denmark. The second edition was published in Danish in 2010 and has been a great success, but as new knowledge and treatments have emerged it was timely to revise the guideline. The recommendations for the primary headaches and facial pain are largely in accordance with the European guidelines produced by the European Academy of Neurology. The guideline should be used a practical tool for use in daily clinical practice for primary care physicians, neurologists with a common interest in headache, as well as other health-care professionals treating headache patients. The guideline first describes how to examine and diagnose the headache patient and how headache treatment is organized in Denmark. This description is followed by sections on the characteristics, diagnosis and treatment of each of the most common primary and secondary headache disorders and trigeminal neuralgia. The guideline includes many tables to facilitate a quick overview. Finally, the particular challenges regarding migraine and female hormones as well as headache in children are addressed.

Objective This meta-analysis evaluates pressure pain sensitivity values in symptomatic and distant pain-free areas comparing individuals with tension-type headache to controls. Databases and data treatment Electronic databases were searched for cross-sectional or prospective case-control studies comparing pressure pain thresholds in patients with tension-type headache to headache-free controls. Data were extracted by three reviewers. The methodological quality was assessed by the Newcastle-Ottawa Quality Assessment Scale. Meta-analyses of trigeminal, extra-trigeminal (neck) and distant pain-free areas in tension-type headache were compared to headache-free controls. Frequency of tension-type headache and gender were taken into account. Results Twenty studies were included. Patients with tension-type headache exhibited lower pressure pain thresholds than headache-free controls: Trigeminal (MD −49.11 kPa, 95% CI −66.05 to −32.17), cervical spine (MD −88.17 kPa, 95% CI −108.43 to −67.92) and distant pain-free areas (MD −98.43 kPa, 95% CI −136.78 to −60.09). Differences were significant for chronic, episodic, and mixed episodic and chronic tension-type headache within the trigeminal and neck (symptomatic areas), but only significant for chronic tension-type headache (MD −102.86, 95% CI −139.47 to −66.25 kPa) for distant pain-free areas. In general, women had lower pressure pain thresholds than men. The methodological quality ranged from fair (45%) to good (40%). The results showed a high heterogeneity and publication bias. Conclusion This first meta-analysis addressing pressure pain thresholds differences in symptomatic and distant pain-free areas between patients with tension-type headache and controls found low to moderate evidence supporting the presence of pressure pain hypersensitivity in the trigeminal and neck areas in tension-type headache in comparison with headache-free controls. Sensitivity to pressure pain was widespread only in chronic, not episodic, tension-type headache (moderate evidence). Registration number: https://doi.org/10.17605/OSF.IO/R29HY

Migraine is the second largest cause of years lost to disability globally among all diseases, with a worldwide prevalence over 1 billion. Despite the global burden of migraine, few classes of therapeutics have been specifically developed to combat migraine. After 30 years of translational research, calcitonin gene-related peptide (CGRP) inhibitors have emerged as a promising new tool in the prevention of migraine. Like all new therapeutics; however, we have limited real-world experience and CGRP has several known systemic actions that warrant consideration. This article provides a narrative review of the evidence for CGRP antagonists and summarises the known and potential side effects that should be considered.

Importance Medication overuse headache (MOH) is a disabling, globally prevalent disorder representing a well-known and debated clinical problem. Evidence for the most effective treatment strategy is needed. Objective To compare 3 treatment strategies for MOH. Design, Setting, and Participants This open-label, randomized clinical trial with 6 months of follow-up was conducted in the tertiary sector at the Danish Headache Center, Glostrup, from October 25, 2016, to June 28, 2019. Of 483 patients with MOH referred during the inclusion period, 195 met the criteria consisting of migraine and/or tension-type headache, 18 years or older, eligibility for outpatient treatment, no severe physical or psychiatric disorder, no other addiction, and not pregnant or breastfeeding. Of these, 75 refused participation and 120 were included. Data were analyzed from July 3 to September 6, 2019. Interventions Random assignment (1:1:1 allocation) to 1 of the 3 outpatient treatments consisting of (1) withdrawal plus preventive treatment, (2) preventive treatment without withdrawal, or (3) withdrawal with optional preventive treatment 2 months after withdrawal. Main Outcomes and Measures The primary outcome was change in headache days per month after 6 months. Predefined secondary outcomes were change in monthly migraine days, use of short-term medication, pain intensity, number of responders, patients with remission to episodic headache, and cured MOH. Results Of 120 patients, 102 (mean [SD] age, 43.9 [11.8] years; 81 women [79.4%]) completed the 6-month follow-up. Headache days per month were reduced by 12.3 (95% CI, 9.3-15.3) in the withdrawal plus preventive group, by 9.9 (95% CI, 7.2-12.6) in the preventive group, and by 8.5 (95% CI, 5.6-11.5) in the withdrawal group (P = .20). No difference was found in reduction of migraine days per month, use of short-term medication, or headache intensity. In the withdrawal plus preventive group, 23 of 31 patients (74.2%) reverted to episodic headache, compared with 21 of 35 (60.0%) in the preventive group and 15 of 36 (41.7%) in the withdrawal group (P = .03). Moreover, 30 of 31 patients (96.8%) in the withdrawal plus preventive group were cured of MOH, compared with 26 of 35 (74.3%) in the preventive group and 32 of 36 (88.9%) in the withdrawal group (P = .03). These findings corresponded to a 30% (relative risk, 1.3; 95% CI, 1.1-1.6) increased chance of MOH cure in the withdrawal plus preventive group compared with the preventive group (P = .03). Conclusion and Relevance All 3 treatment strategies were effective, but based on these findings, withdrawal therapy combined with preventive medication from the start of withdrawal is recommended as treatment for MOH. Trial Registration ClinicalTrials.gov Identifier:NCT02993289

Introduction Persistent idiopathic facial pain (PIFP) is a poorly understood chronic orofacial pain disorder and a differential diagnosis to trigeminal neuralgia. To address the lack of systematic studies in PIFP we here report clinical characteristics and neuroimaging findings in PIFP. Methods Data collection was prospective and standardized in consecutive PIFP patients. All patients underwent 3.0 MRI. Results In a cohort of 53 PIFP patients, the average age of onset was 44.1 years. PIFP was found in more women 40 (75%) than men 13 (25%), p Conclusion PIFP is separated from trigeminal neuralgia both with respect to the clinical characteristics and neuroimaging findings, as NVC was not associated to PIFP.

Following publication of the original article [1], the authors notified us of some misreported data due to the publication of the EVOLVE-2 trial (Cephalalgia. 2018;38:1442–1454), which substantially changed the level of evidence of galcanezumab for the prevention of episodic migraine. All changes are marked in bold and with red in Figure 1 and Figure 2. Please note that the final recommendations remain unchanged.

Background Medication-overuse headache leads to high disability and decreased quality of life, and the best approach for withdrawal has been debated. Aim To compare change in disability and quality of life between two withdrawal programs. Methods We randomized medication-overuse headache patients to program A (two months without acute analgesics or migraine medications) or program B (two months with acute medications restricted to two days/week) in a prospective, outpatient study. At 6 and 12 months, we measured disability and headache burden by the Headache Under-Response to Treatment index (HURT). We estimated quality of life by EUROHIS-QOL 8-item at 2-, 6-, and 12-month follow-up. Primary endpoint was disability change at 12 months. Results We included 72 medication-overuse headache patients with primary migraine and/or tension-type headache. Fifty nine completed withdrawal and 54 completed 12-month follow-up. At 12-month follow-up, 41 patients completed HURT and 38 completed EUROHIS-QOL 8-item. Disability reduction was 25% in program-A and 7% in program-B ( p = 0.027). Headache-burden reduction was 33% in program-A and 3% in program-B ( p = 0.005). Quality of life was increased by 8% in both programs without significant difference between the programs ( p = 0.30). At 2-month follow-up, quality of life increased significantly more in program-A than program-B ( p = 0.006). Conclusion Both withdrawal programs reduced disability and increased quality of life. Withdrawal without acute medication was the most effective in reducing disability in medication-overuse headache patients. Trial registration Clinicaltrials.gov (NCT02903329).

BACKGROUND: Trigeminal neuralgia (TN) is an extremely painful condition, which can be difficult to diagnose and treat. In Europe, TN-patients are managed by many different specialities. Therefore, there is a great need for comprehensive European guidelines for management of TN. The European Academy of Neurology asked an expert panel to develop recommendations for a series of questions that are essential for daily clinical management of patients with TN.METHODS: We performed a systematic review of the literature and developed recommendations based on GRADE, where feasible, if not a good practice statement was given.RESULTS: We recommend the use of the most recent classification system, which diagnoses TN as primary TN, either classical or idiopathic depending on the degree of neurovascular contact, or as secondary TN caused by pathology other than neurovascular contact. An MRI, using a combination of three high-resolution sequences, should be performed as part of work up in TN patients, because no clinical characteristics can exclude secondary TN. If MRI is not possible, trigeminal reflexes can be used. Neurovascular contact plays an important role in primary TN, but demonstration of a neurovascular contact should not be used to confirm the diagnosis of TN. Rather, it may help to decide if and when a patient should be referred for microvascular decompression. In acute exacerbations of pain, intravenous infusion of fosphenytoin or lidocaine can be used. For long-term treatment we recommend carbamazepine or oxcarbazepine as drugs of first choice. Lamotrigine, gabapentin, botolinum toxin type A, pregabalin, baclofen and phenytoin may be used either alone or as add-on therapy. We recommend that patients should be offered surgery if pain is not sufficiently controlled medically or if medical treatment is poorly tolerated. Microvascular decompression is recommended as first-line surgery in patients with classical TN. No recommendation can be given for choice between any neuroablative treatments or between them and microvascular decompression in patients with idiopathic TN. Neuroablative treatments should be the preferred choice if MRI does not demonstrate any neurovascular contact. Treatment for patients with secondary TN should in general follow the same principles as for primary TN. In addition to medical and surgical management, we recommend that patients are offered psychological and nursing support.CONCLUSIONS: Compared with previous TN guidelines, there are important changes regarding diagnosis and imaging. These allow better characterization of patients and help in decision making regarding the planning of medical and surgical management. Recommendations on pharmacological and surgical management have been updated. There is a great need for future research on all aspects of TN, including pathophysiology and management. This article is protected by copyright. All rights reserved.

Background Prognosis of medically treated trigeminal neuralgia patients is assumed to be poor, but the evidence is lacking. Thus, prospective real-life studies of medical management of trigeminal neuralgia are warranted. Methods This was an observational study. Patients were consecutively enrolled in a structured management program at a specialist centre for facial pain. Optimisation of medical treatment, physiotherapy, psychotherapy, and advice from trained nurses, were parts of the program. Medically intractable patients were referred for neurosurgery. Data-collection was prospective using standardised schemes and patient surveys. The aim was to describe the two-year outcome of medical treatment at the specialist centre. The primary outcome was a 50% reduction in the overall burden of pain according to a Numerical Rating Scale (NRS) after two years. Results A total of 186 primary TN patients were enrolled in the program of which 103 patients remained medically managed and completed the two-year follow-up. Fifty patients were treated surgically within the first two years of follow-up. Half of the medically managed patients (53 (51%)), had more than a 50% reduction in the overall burden of pain over the two-year period. The overall burden of pain on NRS decreased from mean 5.34 to 3.00, p

BACKGROUND AND AIM: Monoclonal antibodies acting on the calcitonin gene-related peptide or on its receptor are new drugs to prevent migraine. Four monoclonal antibodies have been developed: one targeting the calcitonin gene-related peptide receptor (erenumab) and three targeting the calcitonin gene-related peptide (eptinezumab, fremanezumab, and galcanezumab). The aim of this document by the European Headache Federation (EHF) is to provide an evidence-based and expert-based guideline on the use of the monoclonal antibodies acting on the calcitonin gene-related peptide for migraine prevention.METHODS: The guideline was developed following the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. The working group identified relevant questions, performed systematic review and analysis of the literature, assessed the quality of available evidence, and wrote recommendations. Where the GRADE approach was not applicable, expert opinion was provided.RESULTS: We found low to high quality of evidence to recommend eptinezumab, erenumab, fremanezumab, and galcanezumab in patients with episodic migraine and medium to high quality of evidence to recommend erenumab, fremanezumab, and galcanezumab in patients with chronic migraine. For several clinical questions, there was not enough evidence to provide recommendations using the GRADE approach and recommendations relied on experts' opinion.CONCLUSION: Monoclonal antibodies acting on the calcitonin gene-related peptide are new drugs which can be recommended for migraine prevention. Real life data will be useful to improve the use of those drugs in clinical practice.

Background Previous studies found low serum levels of nociceptin in migraine patients but high serum levels of calcitonin gene-related peptide (CGRP). CGRP can elicit migraine-like headache. Medication-Overuse Headache (MOH) often has migraine features and can mimic chronic migraine. We therefore hypothesized that as in migraine, serum levels of nociceptin would be lower and CGRP serum levels higher in MOH patients compared with those in healthy volunteers. We hypothesized that the serum levels would normalize after detoxification. Methods Seventeen MOH patients, hereof 70.6% with chronic migraine and MOH, and 30 sex and age matched headache-free controls were included. MOH patients underwent a 2-month outpatient detoxification program and after 6 months, 10 patients and 19 controls were retested. Blood samples were analyzed blinded. Results We found no differences in the levels of nociceptin and CGRP between MOH patients and controls (P = 0.65 and P = 0.59). The mean headache frequency reduction was 43% and 70% of patients reverted to episodic headache after 6 months, but the levels of nociceptin and CGRP were unchanged (P = 0.71 and P = 0.82). Conclusion In contrast to previous findings in migraine patients, we found normal serum levels of nociceptin and CGRP in MOH patients. Thus, we find no evidence that the increased headache frequency of MOH patients could be caused by altered nociceptin and CGRP levels. This underlines the importance of identifying medication overuse in chronic headache and treating the MOH.

IntroductionThere is a lack of high-quality prospective, systematic studies using independent assessors of outcome of microvascular decompression as treatment for trigeminal neuralgia.MethodsClinical characteristics and outcome data were recorded prospectively from consecutive classical trigeminal neuralgia patients, using standardized interviews. Degree of neurovascular contact was evaluated by a 3.0 Tesla MRI blinded to symptomatic side. Patients were assessed before and 12 months after surgery by a neurologist.ResultsTwenty-six men and 33 women completed 12 months follow-up. Forty-one patients (69%) had an excellent outcome (no pain, no medication). Ten (18%) patients had a good outcome. Eight (12%) patients had no improvement or had worsening of pain. MRI showed neurovascular contact with morphological changes in 34 patients (58%). Odds ratio between neurovascular contact with morphological changes and excellent outcome was 4.4 (Cl 1.16–16.26), p = 0.029. Odds ratio between male sex and excellent outcome was 11.38 (Cl 2.12–59.52), p = 0.004. No significant association was found between excellent outcome and concomitant persistent pain, current age or disease duration.ConclusionNeurovascular contact with morphological changes and male sex are positive predictive factors for outcome of microvascular decompression. The findings enable clinicians to better inform patients before surgery.

Background There is lack of evidence on how to detoxify medication-overuse headache. Aim To compare the effect of complete stop of acute medication with restricted intake. Methods Medication-overuse headache patients were included in a prospective, outpatient study and randomized to two months’ detoxification with either a) no analgesics or acute migraine-medication (program A), or b) acute medication restricted to two days/week (program B). Detoxification was followed by preventives if indicated. Patients were followed up at 2, 6 and 12 months. Percentage reduction in headache days/month after 6 months was the primary outcome. Results We included 72 medication-overuse headache patients with a primary migraine and/or tension-type headache diagnosis. Fifty-nine completed detoxification, 58 (81%) were followed up at month 6 and 53 (74%) at month 12. At month 6, program A reduced headache days/month by 46% (95% CI 34–58) compared with 22% (95% CI 11–34) in program-B ( p = 0.005), and 70% in program A versus 42% in program B were reverted to episodic headache ( p = 0.04). Migraine-days/month were reduced by 7.2 in program A ( p Conclusion Both detoxification programs were very effective. Detoxification without analgesics or acute migraine-medication was the most effective program. Trial registration Clinicaltrials.gov (NCT02903329).

Background Previous studies demonstrated that a severe neurovascular contact (NVC) causing displacement or atrophy of the trigeminal nerve is highly associated with classical trigeminal neuralgia (TN). There are no studies describing the association between the clinical characteristics of TN and severe NVC. Methods Clinical characteristics were prospectively collected from consecutive TN patients using semi-structured interviews in a cross-sectional study design. We evaluated 3.0 Tesla MRI blinded to the symptomatic side. Results We included 135 TN patients. Severe NVC was more prevalent in men (75%) compared to women (38%) ( p Conclusions Severe NVC was much more prevalent in men than in women, who may more often have other disease etiologies causing or contributing to TN. Severe NVC was not associated with age or with duration of disease.

Summary Background Current standard of care for trigeminal neuralgia is treatment with the sodium channel blockers carbamazepine and oxcarbazepine, which although effective are associated with poor tolerability and the need for titration. BIIB074, a Nav1.7-selective, state-dependent sodium-channel blocker, can be administered at therapeutic doses without titration, and has shown good tolerability in healthy individuals in phase 1 studies. We therefore assessed the safety and efficacy of BIIB074 in patients with trigeminal neuralgia in a phase 2a study. Methods We did a double-blind, multicentre, placebo-controlled, randomised withdrawal phase 2a trial in 25 secondary care centres in Denmark, Estonia, France, Germany, Italy, Latvia, Lithuania, Romania, South Africa, Spain, Switzerland, and the UK. After a 7-day run-in phase, eligible patients aged 18–80 years with confirmed trigeminal neuralgia received open-label, BIIB074 150 mg three times per day, orally, for 21 days. Patients who met at least one response criteria were then randomly assigned (1:1) to BIIB074 or placebo for up to 28 days in a double-blind phase. We used an interactive web response system to assign patients with a computer-generated schedule, with stratification (presence or absence of existing pain medication). Patients, clinicians, and assessors were masked to treatment allocation. The primary endpoint was the difference between groups in the number of patients classified as treatment failure during the double blind phase assessed in the modified intention-to-treat population. We assessed safety in all patients who received one or more doses of BIIB074. This study is registered with ClinicalTrials.gov (NCT01540630) and EudraCT (2010-023963-16). Findings The first patient was enrolled on April 23, 2012, and the last patient completed the study on February 26, 2014. We enrolled 67 patients into the open-label phase; 44 completed open-label treatment, and 29 were randomly assigned to double-blind treatment (15 to BIIB074 and 14 to placebo). During the double-blind phase, five (33%) patients assigned to BIIB074 versus nine (64%) assigned to placebo were classified as treatment failures (p=0·0974). BIIB074 was well tolerated, with similar adverse events in the double-blind phase to placebo. Headache was the most common adverse event with BIIB074 in the open-label phase (in 13 [19%] of 67 patients), followed by dizziness (in six [9%] patients). In the double-blind phase, headache, pyrexia, nasopharyngitis, sleep disorder, and tremor were the most frequent adverse events in patients assigned to BIIB074 (in one [7%] of 15 patients for each event), and headache, dizziness, diarrhoea, and vomiting were the most frequent adverse events in patients assigned to placebo (in one [7%] of 14 patients for each event). No severe or serious adverse events were reported in the BIIB074 group during the double-blind phase. One patient assigned to placebo reported intestinal adhesions with obstruction as a severe and serious adverse event, which was considered as unrelated to study medication. Interpretation The primary endpoint of treatment failure was not significantly lower in the BIIB074 group than in the placebo group. However, our findings provide a basis for continued investigation of BIIB074 in patients with trigeminal neuralgia in future clinical trials. Funding Convergence Pharmaceuticals.

OBJECTIVES People with migraine and tension-type headache (TTH) have psychiatric comorbidities. We aimed to test differences in mental health constructs by type and frequency of primary headache and associated pain sensitivity. MATERIALS AND METHODS Data on headache features, neuroticism (Eysenck Personality Questionnaire) and depression (Major Depression Inventory) were obtained from 547 individuals classified into chronic (≥15) or episodic (

Introduction Trigeminal neuralgia (TN) is characterized by touch-evoked unilateral brief shock-like paroxysmal pain in one or more divisions of the trigeminal nerve. In addition to the paroxysmal pain, some patients also have continuous pain. TN is divided into classical TN (CTN) and secondary TN (STN). Etiology and pathophysiology Demyelination of primary sensory trigeminal afferents in the root entry zone is the predominant pathophysiological mechanism. Most likely, demyelination paves the way for generation of ectopic impulses and ephaptic crosstalk. In a significant proportion of the patients, the demyelination is caused by a neurovascular conflict with morphological changes such as compression of the trigeminal root. However, there are also other unknown etiological factors, as only half of the CTN patients have morphological changes. STN is caused by multiple sclerosis or a space-occupying lesion affecting the trigeminal nerve. Differential diagnosis and treatment Important differential diagnoses include trigeminal autonomic cephalalgias, posttraumatic or postherpetic pain and other facial pains. First line treatment is prophylactic medication with sodium channel blockers, and second line treatment is neurosurgical intervention. Future perspectives Future studies should focus on genetics, unexplored etiological factors, sensory function, the neurosurgical outcome and complications, combination and neuromodulation treatment as well as development of new drugs with better tolerability.

Objective To describe the clinical characteristics in classical trigeminal neuralgia (TN) with concomitant persistent pain and to investigate whether TN with concomitant persistent pain represents a distinct phenotype. Background There has been much debate about the possible pathophysiological and clinical importance of concomitant persistent pain in TN. This has led to subgrouping of TN into forms with and without concomitant persistent pain in the recent 3rd International Classification of Headache Disorders beta classification. Methods In this cross-sectional study, data on the clinical characteristics were systematically and prospectively collected from consecutive TN patients. Results A total of 158 consecutive TN patients were included. Concomitant persistent pain was present in 78 patients (49%). The average intensity of concomitant persistent pain was 4.6 (verbal numerical rating scale). The concomitant persistent pain was present at onset or early in the disease course. Patients with concomitant persistent pain were on average 6.2 (P = .008) years younger at onset, but the 2 groups had the same duration of disease (P = .174). There was a preponderance of women in TN with (P

Objective The objective of this article is to investigate whether headache-related disability, depression and anxiety can be reduced by detoxification and prophylactic treatment in patients with medication-overuse headache (MOH). Methods Patients with MOH were included from six centres in Europe and Latin America in a seven-month cohort study. Before and six months after treatment, the degree of disability was measured by the Migraine Disability Assessment (MIDAS) questionnaire, while anxiety and depression were measured by the Hospital Anxiety and Depression Scale (HADS). Results A total of 694 patients with MOH were included, of whom 492 completed the study. Headache days were reduced by 58.4% from 23.6 to 9.8 days per month at six months ( p Conclusions Disability, depression and anxiety were considerably reduced in patients with MOH by detoxification and prophylactic treatment. This emphasises the urgent need for increased awareness about avoiding overuse of headache medications and demonstrates that not only headache frequency but also disability are remarkably improved by adequate intervention.

BackgroundHuman and animal models suggest that central sensitisation plays a role in medication-overuse headache (MOH). We aimed to study pain perception in MOH patients before and a year after withdrawal.MethodsWe examined pain perception in 35 MOH patients before and two, six and 12 months after detoxification. For baseline comparison, we tested 40 healthy controls. We measured cephalic and extra-cephalic pressure-pain thresholds and supra-threshold pressure-pain scores and extra-cephalic pain thresholds, supra-threshold pain scores and temporal summation for electrical stimulation.ResultsOf the 35 patients, 21 patients completed the entire study and remained cured of MOH. Statistically significant differences between patients and healthy controls were found in cephalic pressure-pain thresholds (137.3 kPa vs. 170 kPa, p ConclusionThe central nervous system is sensitised in patients with MOH. For the first time we demonstrate that the pain perception continues to normalise up to a year after detoxification. This emphasises the importance of detoxification and follow-up to prevent relapse.

Objective To examine whether detoxifying patients with medication-overuse headache can reduce long-term medication costs. Background Direct costs of medications in medication-overuse headache have been reported to be very high but have never been calculated on the basis of exact register data. Long-term economic savings obtained by detoxification have never been investigated. Methods We conducted a registry-based observational retrospective follow-up study on 336 medication-overuse headache patients treated and discharged from the Danish Headache Center over a 2-year period. By means of the Danish Register of Medicinal Product Statistics, we collected information on the costs and use of prescription-only medication 1 year before admission and 1 year after discharge from Danish Headache Center. Results The average medication costs per patient per year decreased with 24%, from US$971 before treatment to US$737 after (P = .001), and the average medication use decreased with 14.4% (P = .02). Savings were most pronounced for patients overusing triptans. In this group, the average medication costs per patient per year decreased with 43% (P

The diagnostic criteria of the third International Classification of Headache Disorders state that there should be no neurological deficits in patients with classical trigeminal neuralgia (TN) at clinical examination. However, studies demonstrating sensory abnormalities at bedside examination in TN patients have questioned this. Our aim was to examine whether TN patients without sensory abnormalities at neurological examination have sensory abnormalities at quantitative sensory testing (QST) and whether there were any QST differences between TN with and without concomitant persistent pain. Thirty-six TN patients were investigated with the standardized QST protocol by the German Research Network on Neuropathic Pain. The investigators were blinded to presence of concomitant persistent pain and symptomatic side. Based on comparison to the German Research Network on Neuropathic Pain controls, z scores were calculated to process frequency analyses and Z-profiles. We found increased mechanical detection threshold on the symptomatic side (47.2% vs 0%, P = 0.008), asymptomatic side (33.3% vs 0%, P = 0.011), and hand (36% vs 0%, P < 0.001) in TN compared with controls. The Z-profiles demonstrated increased mechanical detection threshold on the symptomatic side compared with the asymptomatic side (-2.980 vs -2.166, P = 0.040). Thermal and mechanical hyperalgesia was detected bilaterally in the face and the hand. Trigeminal neuralgia patients with concomitant persistent pain tended to have higher mean z score values compared to TN with purely paroxysmal pain indicative of decreased detection thresholds. Trigeminal neuralgia patients with no sensory abnormalities at neurological examination had generalized subclinical hypoesthesia, which was more pronounced on the symptomatic side, and thermal and mechanical hyperalgesia. This could indicate pain-induced hypoesthesia and sensitization induced by central mechanisms.

Background: Evidence for optimal medication-overuse headache treatment is lacking. Some experts suggest reduced symptomatic medication with prophylactics from the start of withdrawal, while others suggest a two-month drug-free period with multidisciplinary education. Aim: To examine the acceptability, feasibility and outcome of these two regimes in a non-randomised open-label study. Methods: Patients able to undergo outpatient detoxification, with medication-overuse headache that had previously been unsuccessfully treated by specialists and without significant co-morbidities were treated with (A) individual withdrawal with restricted symptomatic medication and prophylactics from Day 1 or (B) a two-month drug-free period and multidisciplinary education in groups. All patients received close one-year follow-up. Results: Eighty-six of 98 patients completed follow-up. Both treatments proved highly effective—80.0% of Group A and 85.4% of Group B were cured of medication-overuse headache. Headache-frequency reduction was 40.2% in Group A and 38.4% in group B. In 48.9% of group A and 48.8% of group B, headache-frequency reduction was >50%. Programme B required fewer resources from the staff and only 61.9% of these patients needed prophylactics after two months compared with 84.8% in programme A. Conclusions: Both structured detoxification programmes proved highly effective with one-year close follow-up in previously treatment-resistant patients with medication-overuse headache. We suggest multidisciplinary education for patients in groups and delaying initiation of prophylactics until after the detoxification.

Objective.— To evaluate the long-term efficacy of a structured, multidisciplinary treatment program in patients who had been treated unsuccessfully for medication overuse headache by specialists in an open-label design. Background.— Medication overuse headache is a common and disabling disease. Management is complicated by substantial treatment failure and relapse, and those who relapse and nonresponders to treatment are often excluded from studies on medication overuse headache. Methods.— Patients with medication overuse headache who had previously been unsuccessfully treated by specialists and referred to a specialized, tertiary headache centre were recruited. They underwent a structured 2-month detoxification program and were subsequently closely followed up for 10 months by a multidisciplinary team of physicians, nurses, physiotherapists, and psychologists. Results.— Eighty-six of 98 patients completed the study. Primary Outcome.— At 12-month follow-up, headache frequency was reduced by 39.3% (P

Headache and facial pain are among the most common, disabling and costly disorders in Europe. Correct diagnosis and treatment is important for achieving a high quality of care. As a national organisation whose role is to educate and advocate for the needs of patients with primary headaches, the Danish Headache Society has set up a task force to develop a set of guidelines for the diagnosis, organisation and treatment of the most common types of headaches and for trigeminal neuralgia in Denmark. The guideline was published in Danish in 2010 and has been a great success. The Danish Headache Society decided to translate and publish our guideline in English to stimulate the discussion on optimal organisation and treatment of headache disorders and to encourage other national headache authorities to produce their own guidelines. The recommendations regarding the most common primary headaches and trigeminal neuralgia are largely in accordance with the European guidelines produced by the European Federation of Neurological Societies. The guideline provides a practical tool for use in daily clinical practice for primary care physicians, neurologists with a common interest in headache, as well as other health-care professionals treating headache patients. The guideline first describes how to examine and diagnose the headache patient and how headache treatment is organised in Denmark. This description is followed by individual sections on the characteristics, diagnosis, differential diagnosis and treatment of each of the major headache disorders and trigeminal neuralgia. The guideline includes many tables to facilitate a quick overview. Finally, the particular problems regarding headache in children and headache in relation to female hormones and pregnancy are described.

BACKGROUND AND PURPOSE: Migrainous infarction (MI), i.e., an ischemic stroke developing during an attack of migraine with aura is rare and the knowledge of its clinical characteristics is limited. ...

Tension-type headache (TTH) is a disorder with high prevalence and significant impact on society. Understanding of pathophysiology of TTH is paramount for development of effective treatments and prevention of chronification of TTH. Our aim was to review the findings from pain perception studies of pathophysiology of TTH as well as to review the research of pathophysiology of TTH. Pain perception studies such as measurement of muscle tenderness, pain detection thresholds, pain tolerance thresholds, pain response to suprathreshold stimulation, temporal summation and diffuse noxious inhibitory control (DNIC) have played a central role in elucidating the pathophysiology of TTH. It has been demonstrated that continuous nociceptive input from peripheral myofascial structures may induce central sensitization and thereby chronification of the headache. Measurements of pain tolerance thresholds and suprathreshold stimulation have shown presence of generalized hyperalgesia in chronic tension-type headache (CTTH) patients, while DNIC function has been shown to be reduced in CTTH. One imaging study showed loss of gray matter structures involved in pain processing in CTTH patients. Future studies should aim to integrate pain perception and imaging to confirm this finding. Pharmacological studies have shown that drugs like tricyclic anti-depressant amitriptyline and nitric oxide synthase inhibitors can reverse central sensitization and the chronicity of headache. Finally, low frequency electrical stimulation has been shown to rapidly reverse central sensitization and may be a new modality in treatment of CTTH and other chronic pain disorders.

Background: Tension-type headache (TTH) is the most prevalent headache type and is causing a high degree of disability. Treatment of frequent TTH is often difficult. Objectives: To give evidence-based or expert recommendations for the different treatment procedures in TTH based on a literature search and the consensus of an expert panel. Methods: All available medical reference systems were screened for the range of clinical studies on TTH. The findings in these studies were evaluated according to the recommendations of the EFNS resulting in level A, B or C recommendations and good practice points. Recommendations: Non-drug management should always be considered although the scientific basis is limited. Information, reassurance and identification of trigger factors may be rewarding. Electromyography (EMG) biofeedback has a documented effect in TTH, whilst cognitive-behavioural therapy and relaxation training most likely are effective. Physical therapy and acupuncture may be valuable options for patients with frequent TTH, but there is no robust scientific evidence for efficacy. Simple analgesics and non-steroidal anti-inflammatory drugs are recommended for the treatment of episodic TTH. Combination analgesics containing caffeine are drugs of second choice. Triptans, muscle relaxants and opioids should not be used. It is crucial to avoid frequent and excessive use of analgesics to prevent the development of medication-overuse headache. The tricyclic antidepressant amitriptyline is drug of first choice for the prophylactic treatment of chronic TTH. Mirtazapine and venlafaxine are drugs of second choice. The efficacy of the prophylactic drugs is often limited, and treatment may be hampered by side effects.

Neurophysiological testing has become a valuable tool for investigating brain excitability and nociceptive systems in headache disorders. Previous reviews have suggested that most neurophysiological tests have limited value for headache diagnosis, but a vast potential for exploring the pathophysiology of headaches, the central effects of certain pharmacological treatments and phenotype-genotype correlations. Many protocols, however, lack standardization. This meta-analytical review of neurophysiological methods in migraine was initiated by a task force within the EUROHEAD project (EU Strep LSHM-CT-2004-5044837-Workpackage 9). Most of the neurophysiological approaches that have been used in headache patients are reviewed, i.e. evoked potentials, nociception-specific blink reflex, single-fibre electromyography, neuroimaging methods (functional MRI, PET, and voxel-based morphometry) and the nitroglycerin attack-provoking test. For each of them, we summarize the results, analyse the methodological limitations and propose recommendations for improved methodology and standardization of research protocols. The first part is devoted to electrophysiological methods, the second to neuroimaging techniques and the NTG test.

Nociceptive mechanisms in tension-type headache are poorly understood. The aim was to investigate the pain sensitivity of pericranial muscles and a limb muscle in patients with tension-type headache. Experimental muscle pain was induced by standardized infusions of 0.5 ml of 1 M hypertonic saline into two craniofacial muscles (anterior temporalis (TPA) and masseter (MAS)) and a limb muscle (anterior tibial (TA)) in 24 frequent episodic tension-type headache patients (FETTH), 22 chronic tension-type headache patients (CTTH) and 26 age and gender matched healthy subjects. Headache patients were examined twice, both on days with and on days without headache. The pressure pain thresholds (PPTs) were determined before and after infusions. The subjects continuously reported intensity of saline-induced pain on an electronic visual analogue scale (VAS) and the perceived area of pain was drawn on anatomical maps. Headache patients demonstrated significantly lower PPTs, higher saline-evoked VAS pain scores and greater pain areas than healthy subjects at all the tested muscle sites (P0.05). There was a significant gender difference for the PPTs in all three groups of participants (P0.05) and for VAS pain scores in the CTTH patients (P0.05). There was no difference in pain sensitivity between FETTH and CTTH or between patients with or without headache. In conclusion, the present study demonstrates the presence of generalized pain hypersensitivity both in FETTH and CTTH compared to controls which is unrelated to actual headache status and extends to include responses to longer-lasting stimuli which are clinically highly relevant. Gender differences in deep pain sensitivity seem to be a consistent finding both in healthy controls and patients with tension-type headache.

We recently reported an increase in prevalence and frequency of tension-type headache (TTH) over a 12-year period in the young Danish population. The aim of the present study was to analyse whether this increase was related to increased pain sensitivity. The study was a cross-sectional replicate of a large Danish population study. It compared 113 subjects aged 25-36 years in 2001, with 221 comparable subjects in 1989. Tenderness was considerably higher in 2001 than in 1989. When stratified according to presence of headache, the increase in tenderness was clinically and statistically significant only in women with frequent TTH. The pressure pain threshold was significantly lower in 2001 compared with 1989 in women with frequent TTH. The increase in tenderness in the population may predict an even higher prevalence of TTH in future. The changes support the hypothesis of central sensitization in TTH.

Aim To describe the frequency and number of premonitory symptoms (PS) in migraine, the co-occurrence of different PS, and their association with migraine-related factors. Methods In this cross-sectional study, a validated questionnaire was sent to Finnish migraine families between 2002 and 2013 to obtain data on 14 predefined PS, migraine diagnoses, demographic factors, and migraine characteristics. The estimated response rate was 80%. Results Out of 2714 persons, 2223 were diagnosed with migraine. Among these, 77% reported PS, with a mean number of 3.0 symptoms compared to 30% ( p Conclusion PS are experienced by a majority of migraineurs. More severe migraine is associated with a higher burden of PS. Since the material was not entirely representative of the general population of migraineurs, caution should be exercised in generalizing the results.

Background Optimal management of patients with classical trigeminal neuralgia (TN) requires specific treatment programs and close collaboration between medical, radiological and surgical specialties. Organization of such treatment programs has never been described before. With this paper we aim to describe the implementation and feasibility of an accelerated cross-speciality management program, to describe the collaboration between the involved specialties and to report the patient flow during the first 2 years after implementation. Finally, we aim to stimulate discussions about optimal management of TN. Methods Based on collaboration between neurologists, neuroradiologists and neurosurgeons a standardized program for TN was implemented in May 2012 at the Danish Headache Center (DHC). First out-patient visit and subsequent 3.0 Tesla MRI scan was booked in an accelerated manner. The MRI scan was performed according to a special TN protocol developed for this program. Patients initially referred to neurosurgery were re-directed to DHC for pre-surgical evaluation of diagnosis and optimization of medical treatment. Follow-up was 2 years with fixed visits where medical treatment and indication for neurosurgery was continuously evaluated. Scientific data was collected in a structured and prospective manner. Results From May 2012 to April 2014, 130 patients entered the accelerated program. Waiting time for the first out-patient visit was 42 days. Ninety-four percent of the patients had a MRI performed according to the special protocol after a mean of 37 days. Within 2 years follow-up 35 % of the patients were referred to neurosurgery after a median time of 65 days. Five scientific papers describing demographics, clinical characteristics and neuroanatomical abnormalities were published. Conclusion The described cross-speciality management program proved to be feasible and to have acceptable waiting times for referral and highly specialized work-up of TN patients in a public tertiary referral centre for headache and facial pain. Early high quality MRI ensured correct diagnosis and that the neurosurgeons had a standardized basis before decision-making on impending surgery. The program ensured that referral of the subgroup of patients in need for surgery was standardized, ensured continuous evaluation of the need for adjustments in pharmacological management and formed the basis for scientific research.

This open study evaluates the effectiveness and safety of topiramate for the prophylaxis of chronic tension-type headache. Fifty-one patients were enrolled, of whom 46 completed 24 weeks of treatment with topiramate. Daily dosing was titrated from 25 mg to 100 mg by treatment week 4. The primary efficacy parameter was headache frequency at weeks 13-24 compared with baseline. Headache frequency declined from 23.50 ± 5.32 days (baseline, mean, SD) to 12.58 ± 6.28 days at weeks 13-24 ( P < 0.0001), with frequency of severe headaches dropping from 8.18 to 3.14 days ( P < 0.0001). The average headache intensity dropped from 6.13 to 2.07 on the visual analogue scale ( P < 0.0001). These parameters were not significantly reduced at weeks 5-12. A 50% reduction in headache frequency was achieved in 73% of patients at weeks 13-24. Also improved were mood, sleep, quality of life (all parameters, P < 0.0001) as well as the Beck Depression Inventory-II ( P < 0.0001). In addition, a highly significant weight loss of 2.14 kg (mean) was observed between baseline (71.64 ± 10.65 kg) and week 24 [69.50 ± 10.04 kg (SD)] ( P < 0.0001). There were only few side-effects, none of these rated severe. The results provide preliminary confirmation of the efficacy and tolerability of topiramate in the prophylaxis of chronic tension-type headache.

Central sensitization is thought to play an important role in the chronification of tension-type headache and in the maintenance and exacerbation of the migraine attack. It has, however, almost exclusively been studied in highly selected patients from headache clinics. The aim of the present study was to evaluate pain perception in primary headaches in the general population. Stimulus–response functions for pressure versus pain, tenderness and pressure pain thresholds were studied in a random sample of 523 adults from the general population. All results were controlled for the effects of age and gender. The area under the stimulus–response function was increased in chronic- and frequent episodic tension-type headache compared with subjects without headache (p

Tension-type headache is the most common type of headache and, in its chronic form, one of the most neglected and difficult types of headache to treat. Recently published data will be reviewed.The prevalence of frequent tension-type headache increased significantly from 1989 to 2001, and several risk factors have been identified. The incidence decreases markedly with age. The prognosis is fairly favorable for the episodic forms. Chronic tension-type headache, coexisting migraine, sleep problems and not being married were identified as risk factors for a poor outcome. Previous reports of sensitization of the central nervous system in patients with chronic tension-type headache were confirmed by the findings of generalized pain hypersensitivity both in skin and in muscles, and of a decrease in the volume of gray matter in brain structures. A promising new animal model of tension-type headache has been developed. In addition, the efficacy of a prophylactic drug, mirtazapine, with fewer side-effects than the tricyclic antidepressants has been demonstrated.The new data on the prevalence, incidence and prognosis of tension-type headache are valuable for health care planning and in daily clinical practice. The increased knowledge with regard to abnormal central pain modulation, together with the development of an animal model, hold promise for much-needed improvements in the understanding of pathophysiological mechanisms and treatment.