Trigeminal neuralgia.

Trigeminal neuralgia (TN) is a facial pain disorder characterized by intense and paroxysmal pain that profoundly affects quality of life and presents complex challenges in diagnosis and treatment. TN can be categorized as classical, secondary and idiopathic. Epidemiological studies show variable incidence rates and an increased prevalence in women and in the elderly, with familial cases suggesting genetic factors. The pathophysiology of TN is multifactorial and involves genetic predisposition, anatomical changes, and neurophysiological factors, leading to hyperexcitable neuronal states, central sensitization and widespread neural plasticity changes. Neurovascular compression of the trigeminal root, which undergoes major morphological changes, and focal demyelination of primary trigeminal afferents are key aetiological factors in TN. Structural and functional brain imaging studies in patients with TN demonstrated abnormalities in brain regions responsible for pain modulation and emotional processing of pain. Treatment of TN involves a multifaceted approach that considers patient-specific factors, including the type of TN, with initial pharmacotherapy followed by surgical options if necessary. First-line pharmacological treatments include carbamazepine and oxcarbazepine. Surgical interventions, including microvascular decompression and percutaneous neuroablative procedures, can be considered at an early stage if pharmacotherapy is not sufficient for pain control or has intolerable adverse effects or contraindications.

Challenges in the management of new daily persistent headache at a tertiary headache center-A retrospective real-world evidence study.

OBJECTIVE: In this retrospective cross-sectional real-world evidence study from the Danish Headache Center (DHC), a national tertiary headache center in Denmark, we sought to identify potential pharmacological agents for the treatment of new daily persistent headache (NDPH). BACKGROUND: NDPH is an enigmatic headache disorder with abrupt onset and chronic duration for which evidence-based treatments are lacking. NDPH is a diagnosis of exclusion, for which secondary headaches must be ruled out and the etiology remains idiopathic. The sparse investigations of this disorder have not yielded a pathophysiological basis and no effective treatment for NDPH has been found. METHODS: All patients with an NDPH diagnosis at the DHC were enrolled (n = 64). First, we reviewed the records of all patients with an NDPH diagnosis to evaluate whether they fulfilled the diagnostic criteria. Next, we extracted all the trialled acute and prophylactic pharmacological interventions for the included patients. Then, pharmacological interventions that had been tried in ≥ 20 patients were analyzed post hoc with efficacy as the outcome, which was stratified in five effect categories ("no effect," "partial effect," "full effect," "partial effect and cessation due to adverse events," and "full effect and cessation due to adverse events"). Descriptive statistical analysis was performed, and the results were schematically presented (see Table 2). RESULTS: Fifty-one patients out of 64 were found to fulfill NDPH criteria and were included in the study. The drugs tried by ≥ 20 patients were amitriptyline (n = 34), candesartan (n = 27), and mirtazapine (n = 20). No patients experienced a complete effect with these drugs while 9% (3/34), 26% (7/27), and 15% (3/20) experienced a partial effect with no adverse events that led to treatment discontinuation, respectively. The remaining patients experienced either no effect or a partial effect with adverse events leading to treatment discontinuation. CONCLUSION: In this study we add real-world evidence to suggest that prophylactic drugs conventionally used for treating chronic migraine and chronic tension-type headache have limited utility for treating NDPH; however, a partial response in 26% of patients using candesartan and 15% of patients using mirtazapine warrants further investigation in randomized double-blinded placebo-controlled trials.

Pericranial Muscle Stiffness, Pain Thresholds, and Tenderness during a Treatment Cycle of OnabotulinumtoxinA for Chronic Migraine Prevention.

BACKGROUND: Treatment with OnabotulinumtoxinA (BoNT-A) is effective as a preventive treatment for chronic migraine (CM). Preclinical studies suggest that the mechanism of action of BoNT-A in migraine is based on blocking unmyelinated C fibers. We aimed to investigate whether the muscle-relaxing effect of BoNT-A is associated with the preventive mechanism in patients with chronic migraine by measuring the stiffness, pain thresholds, and tenderness of the BoNT-A-applied muscles. METHODS: A total of 22 patients with CM who were already in BoNT-A treatment participated in this longitudinal prospective study. Pericranial muscle stiffness was measured using ultrasound shear wave elastography, which measures the speed of shear waves propagating through the muscle. Pressure pain thresholds (PPT) were obtained via algometry, and muscle tenderness was measured via manual palpation. Measurements were made before BoNT-A injections and six weeks after the treatment. The measurements were performed while the muscles were maximally relaxed. The patients also completed daily diaries on headache and neck pain. RESULTS: No change was observed in muscle stiffness (p = 0.737) or pericranial muscle tenderness (p = 0.400). The PPT over the trapezius muscles increased from 250 kPa before treatment to 304 kPa six weeks after treatment (p = 0.027). No change was observed on the temporalis muscles (p = 0.200) nor the non-dominant index finger (p = 0.067). BoNT-A decreased neck pain (p = 0.008) and headache (p = 0.007). CONCLUSIONS: The findings suggest that BoNT-A leads to the desensitization of cutaneous and muscle nociceptors in the head and neck regions, whereas muscle relaxation might not be an important part of the anti-migraine effect.

Comparison of the blink reflex in classical and idiopathic trigeminal neuralgia.

BACKGROUND: Previous findings indicate that the blink reflex is useful to distinguish between primary (classical/idiopathic) and secondary trigeminal neuralgia. No prior studies have investigated whether the blink reflex could identify differences in electrophysiological responses between classical and idiopathic trigeminal neuralgia. With this in mind, we investigated the blink reflex in a cohort of classical and idiopathic trigeminal neuralgia patients. METHODS: Participants were consecutively enrolled in the study. According to magnetic resonance imaging findings, the patients were subgrouped into either classical or idiopathic trigeminal neuralgia. Assessors were blinded to the subgroup and pain side, and the blink reflex was examined to assess R1 and R2 latencies, as well as the area under the curve. RESULTS: The study group constituted of 55 patients with primary trigeminal neuralgia: 25 patients with classical trigeminal neuralgia and 30 patients with idiopathic trigeminal neuralgia. None of the blink reflex latencies (R1 and R2) or the area under the curve significantly differed between the two subgroups when adjusted for age and sex (p > 0.05). CONCLUSIONS: Our findings suggest that the blink reflex cannot be used to differentiate classical and idiopathic trigeminal neuralgia patients, and that both subgroups may share common pathophysiological mechanisms.Trial Registration: ClinicalTrials.gov Identifier: NCT05328661.

Real-world evidence on the economic implications of CGRP-mAbs as preventive treatment of migraine.

BACKGROUND: Calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) are approved in Europe as preventive treatment of migraine in patients with at least four monthly migraine days. Migraine gives rise to direct healthcare expenditures, but most of the economic burden of migraine is socioeconomic. Evidence on the socioeconomic implications of CGRP-mAbs is, however, limited. There is an increasing interest in supplementing evidence from randomised controlled trials (RCTs) with real-world evidence (RWE) to aid clinical decision making and inform decision making for migraine management. The objective of this study was to generate RWE on the health economic and socioeconomic implications of administering CGRP-mAbs to patients with chronic migraine (CM) and episodic migraine (high-frequency episodic migraine (HFEM), and low-frequency episodic migraine (LFEM)). METHODS: Real-world data (RWD) on Danish patients with CM, HFEM, and LFEM were collected via two Danish patient organisations and two informal patient networks and used in a tailored economic model. Treatment effects of CGRP-mAbs on health economic and socioeconomic outcomes were estimated using a sub-sample of patients with CM who receive CGRP-mAb treatment. RESULTS: A total of 362 patients (CM: 199 [55.0%], HFEM: 80 [22.1%], LFEM: 83 [22.9%]) were included in the health economic model (mean age 44.1 ± 11.5, 97.5% female, 16.3% received treatment with CGRP-mAbs), and 303 patients were included in the socioeconomic model (15.2% received treatment with CGRP-mAbs). Health economic savings from initiating CGRP-mAb treatment totalled €1,179 per patient with CM per year on average (HFEM: €264, LFEM: €175). Socioeconomic gains from initiating CGRP-mAb treatment totalled an average gross domestic product (GDP) gain of €13,329 per patient with CM per year (HFEM: €10,449, LFEM: €9,947). CONCLUSION: Our results indicate that CGRP-mAbs have the potential to reduce both health economic expenditures and the socioeconomic burden of migraine. Health economic savings are used as a basis for health technology assessments (HTAs) of the cost-effectiveness of new treatments, which implies that important socioeconomic gains may not be given enough importance in decision making for migraine management.

Efficacy of surgical treatment in patients with trigeminal neuralgia secondary to multiple sclerosis: A prospective study of 18 cases with evaluation of outcome and complications by independent evaluators.

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.

Pain sensitivity in relation to frequency of migraine and tension-type headache with or without coexistent neck pain: an exploratory secondary analysis of the population study.

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 (<15 headache days/month) headache and controls. TTS, PPTs and the area under the SR curve were compared between subgroups using Generalized Linear Models with pairwise comparisons controlling for age and sex. 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<0.001). Temporal and finger PPTs did not statistically differ among the chronic headache, the episodic headache and controls in individuals with and without neck pain. Temporalis and trapezius SR-functions showed that tenderness was increased in individuals with chronic headache to higher degree than in those with episodic headache, and more so in those with neck pain. 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.

Microvascular decompression in trigeminal neuralgia - a prospective study of 115 patients.

BACKGROUND: Trigeminal neuralgia is a severe facial pain disorder. Microvascular decompression is first choice surgical treatment of patients with classical TN. There exist few prospective studies with an independent evaluation of efficacy and complications after MVD. OBJECTIVES: We aimed to assess outcome and complications after microvascular decompression from our center. METHODS: We prospectively recorded clinical characteristics, outcome, and complications from consecutive patients with either classical or idiopathic (only patients with a neurovascular contact) trigeminal neuralgia undergoing microvascular decompression. Neurovascular contact was evaluated by 3.0 Tesla MRI. Patients were assessed before and 3, 6, 12, and 24 months after surgery by independent assessors. RESULTS: Of 115 included patients, 86% had a clinically significant outcome (i.e., BNI I - BNI IIIb). There was a significant association between an excellent surgical outcome and the male sex (OR 4.9 (CI 1.9-12.8), p = 0.001) and neurovascular contact with morphological changes (OR 2.5 (CI 1.1-6.0), p = 0.036). Significantly more women (12/62 = 19%) than men (2/53 = 4%) had a failed outcome, p = 0.019. The most frequent major complications were permanent hearing impairment (10%), permanent severe hypoesthesia (7%), permanent ataxia (7%), and stroke (6%). Most patients (94%) recommend surgery to others. CONCLUSION: Microvascular decompression is an effective treatment for classical and idiopathic (only patients with a neurovascular contact) trigeminal neuralgia with a high chance of a long-lasting effect. The chance of an excellent outcome was highest in men and in patients with classical trigeminal neuralgia. Complications are relatively frequent warranting thorough patient evaluation and information preoperatively. TRIAL REGISTRATION: Clinical. TRIALS: gov registration no. NCT04445766 .

Telephone follow-up on treatment and patient satisfaction at a Danish tertiary headache center: A prospective study.

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.

Safety and efficacy of erenumab in patients with trigeminal neuralgia in Denmark: a double-blind, randomised, placebo-controlled, proof-of-concept study.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: Novartis.

European Headache Federation guideline on the use of monoclonal antibodies targeting the calcitonin gene related peptide pathway for migraine prevention - 2022 update.

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.

Real-world long-term efficacy and safety of erenumab in adults with chronic migraine: a 52-week, single-center, prospective, observational study.

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.

Treatment experiences and clinical characteristics in migraine and tension-type headache patients before the first visit to a tertiary headache center.

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 < 0.004). 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.

Intravenous fosphenytoin as treatment for acute exacerbation of trigeminal neuralgia: A prospective systematic study of 15 patients.

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 < 0.001), and at day 7 by 5.5 points (p < 0.001). The most common side effects were hypotension and dizziness. 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.

Treatment of medication overuse headache: Effect and predictors after 1 year-A randomized controlled trial.

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 < 0.0001), and only 11/96 patients (11%) relapsed. Reduction in monthly headache days was 10.3 days (95% CI: 6.7-13.9) in the W+P group, 10.8 days (95% CI: 7.6-14) in the P+pW group, and 7.9 days (95% CI: 5.1-10.7) in the W+pP group. No significant differences in treatment effect were seen between the three groups (p = 0.377). After 1 year, 39/96 (41%) had chronic headache. Predictors of chronic headache after 1 year were higher headache frequency (aOR 1.19; 1.09-1.31), more days with acute medication (aOR 1.11; 1.03-1.19), higher pain intensity (aOR 1.04; 1.01-1.08), and depression (aOR 4.7; 1.38-18.95), whereas higher self-rated health (aOR 0.61; 0.36-0.97) and high caffeine consumption (aOR 0.40; 0.16-0.96) were predictors of a lower risk of chronic headache. No adverse events were reported. CONCLUSIONS: All treatment strategies proved effective in treating MOH with a low relapse rate. The W+P strategy leads to the fastest effect, confirming earlier treatment recommendations. Identification of predictors for chronic headache may help identify more complex patients.

Reference programme: diagnosis and treatment of headache disorders and facial pain. Danish Headache Society, 3rd edition, 2020.

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.

Health-related quality of life in tension-type headache: a population-based study.

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 (<15 headache days/month). 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.

Calcitonin gene related peptide in migraine: current therapeutics, future implications and potential off-target effects.

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.