Migraine Outcomes Research Articles

Anxiety and Depressive Symptoms and Disorders in Children and Adolescents With Migraine

Though it is presumed that children and adolescents with migraine are at risk of internalizing symptoms and disorders, high-level summative evidence to support this clinical belief is lacking. To determine if there is an association between internalizing symptoms and disorders and migraine in children and adolescents. A librarian-led, peer-reviewed search was performed using MEDLINE, Embase, PsycINFO, and CINAHL databases (inception to March 28, 2022). Case-control, cohort, and cross-sectional studies on the association between internalizing symptoms and disorders and migraine in children and adolescents 18 years or younger were eligible. Two investigators independently completed abstract and full-text screening, data extraction, and quality appraisal using the Newcastle-Ottawa scales. Studies were pooled with random-effects meta-analyses using standardized mean differences (SMD) or odds ratios (OR) with 95% CIs. Where sufficient data for pooling were unavailable, studies were described qualitatively. The primary outcome was migraine diagnosis; additional outcomes included migraine outcomes and incidence. Associations between these outcomes and internalizing symptoms and disorders were evaluated. The study team screened 4946 studies and included 80 studies in the systematic review. Seventy-four studies reported on the association between internalizing symptoms and disorders and migraine, and 51 studies were amenable to pooling. Meta-analyses comparing children and adolescents with migraine with healthy controls showed: (1) an association between migraine and anxiety symptoms (SMD, 1.13; 95% CI, 0.64-1.63); (2) an association between migraine and depressive symptoms (SMD, 0.67; 95% CI, 0.46-0.87); and (3) significantly higher odds of anxiety disorders (OR, 1.93, 95% CI, 1.49-2.50) and depressive disorders (OR, 2.01, 95% CI, 1.46-2.78) in those with, vs without, migraine. Stratification of results did not reveal differences between clinical vs community/population-based samples and there was no evidence of publication bias. Twenty studies assessing the association between internalizing symptoms or disorders and migraine outcomes (n = 18) or incident migraine (n = 2) were summarized descriptively given significant heterogeneity, with minimal conclusions drawn. In this study, children and adolescents with migraine were at higher risk of anxiety and depression symptoms and disorders compared with healthy controls. It may be beneficial to routinely screen children and adolescents with migraine for anxiety and depression in clinical practice. It is unclear whether having anxiety and depressive symptoms or disorders has an affect on migraine outcomes or incidence.

Development and validation of a novel model for characterizing migraine outcomes within real-world data

BackgroundIn disease areas with ‘soft’ outcomes (i.e., the subjective aspects of a medical condition or its management) such as migraine or depression, extraction and validation of real-world evidence (RWE) from electronic health records (EHRs) and other routinely collected data can be challenging due to how the data are collected and recorded. In this study, we aimed to define and validate a scalable framework model to measure outcomes of migraine treatment and prevention by use of artificial intelligence (AI) algorithms within EHR data.MethodsHeadache specialists defined descriptive features based on routinely collected clinical data. Data elements were weighted to define a 10-point scale encompassing headache severity (1–7 points) and associated features (0–3 points). A test data set was identified, and a reference standard was manually produced by trained annotators. Automation (i.e., AI) was used to extract features from the unstructured data of patient encounters and compared to the reference standard. A threshold of 70% close agreement (within 1 point) between the automated score and the human annotator was considered to be a sufficient extraction accuracy. The accuracy of AI in identifying features used to construct the outcome model was also evaluated and success was defined as achieving an F1 score (i.e., the weighted harmonic mean of the precision and recall) of 80% in identifying encounters.ResultsUsing data from 2,006 encounters, 11 features were identified and included in the model; the average F1 scores for automated extraction were 92.0% for AI applied to unstructured data. The outcome model had excellent accuracy in characterizing migraine status with an exact match for 77.2% of encounters and a close match (within 1 point) for 82.2%, compared with manual extraction scores—well above the 70% match threshold set prior to the study.ConclusionOur findings indicate the feasibility of technology-enabled models for validated determination of soft outcomes such as migraine progression using the data elements typically captured in the real-world clinical setting, providing a scalable approach to credible EHR-based clinical studies.Graphical

Pain sensitivities predict prophylactic treatment outcomes of flunarizine in chronic migraine patients: A prospective study.

We aimed to assess the differences in quantitative sensory testing between chronic migraine and healthy controls and to explore the association between pain sensitivities and outcomes in chronic migraine following preventive treatment. In this prospective open-label study, preventive-naïve chronic migraine and healthy controls were recruited, and cold, heat, mechanical punctate, and pressure pain thresholds over the dermatomes of first branch of trigeminal nerve and first thoracic nerve were measured by quantitative sensory testing at baseline. Chronic migraines were treated with flunarizine and treatment response was defined as ≥50% reduction in the number of monthly headache days over the 12-week treatment period. Eighty-four chronic migraines and fifty age-and-sex-matched healthy controls were included in the analysis. The chronic migraine had higher cold pain thresholds over the dermatomes of the first branch of trigeminal nerve and the first thoracic nerve (p < 0.001 and < 0.001), lower pressure pain thresholds over the dermatomes of the first thoracic nerve (p = 0.003), heat pain thresholds over the dermatomes of the first branch of the trigeminal nerve and the first thoracic nerve (p < 0.001 and p = 0.015) than healthy controls. After treatment, 24/84 chronic migraine had treatment response. The responders with relatively normal pain sensitivity had higher heat pain thresholds over the dermatome of the first branch of the trigeminal nerve (p = 0.002), mechanical punctate pain thresholds over the dermatomes of the first branch of the trigeminal nerve (p = 0.023), and pressure pain thresholds over the dermatomes of the first branch of the trigeminal nerve (p = 0.026) than the hypersensitive non-responders. Decision tree analysis showed that patients with mechanical punctate pain threshold over the dermatomes of the first branch of the trigeminal nerve > 158 g (p = 0.020) or heat pain threshold over the dermatome of the first branch of the trigeminal nerve > 44.9°C (p = 0.002) were more likely to be responders. Chronic migraine were generally more sensitive compared to healthy controls. Preventive treatment with flunarizine should be recommended particularly for chronic migraine who have relatively normal sensitivity to mechanical punctate or heat pain.Trial registration: This study was registered on ClinicalTrials.gov (Identifier: NCT02747940).

QP3: Impact of Pharmacist Interventions on Patient Outcomes in Migraine and Cluster Headaches

"QP3: Impact of Pharmacist Interventions on Patient Outcomes in Migraine and Cluster Headaches." Journal of Pain & Palliative Care Pharmacotherapy, 35(4), p. 236

Erenumab dosage for migraine prevention: An evidence-based narrative review with recommendations.

Therapeutic monoclonal antibodies against the calcitonin gene-related peptide (CGRP) receptor or its ligand have changed the landscape of treatment options for migraine. Erenumab is the first and only fully human monoclonal antibody designed to target and block the CGRP receptor. It is approved by the Food and Drug Administration for preventive treatment of migraine in adults. The recommended dose of erenumab is 70mg monthly, with guidance that some patients may benefit from the 140mg monthly dose. There is a need for information to guide clinical practice on the comparative efficacy and safety of these two dosing options. To evaluate therapeutic and tolerability differences between erenumab 70 and 140mg based on evidence from published literature. This narrative review evaluates therapeutic and tolerability differences between erenumab 70 and 140mg based on a literature search using PubMed interface, Embase and Ovid MEDLINE(R) databases. The key search terms included migraine, AMG 334, AMG334, erenumab, erenumab-aooe, and Aimovig. The search was limited to English language articles or conference abstracts published up to May 2021. From the literature search, we retrieved 23 relevant articles/conference abstracts (19 articles [5 randomized, double-blind studies] and 4 conference abstracts) for inclusion in this narrative review. Although the recommended starting dosage of erenumab is 70mg, this narrative review of the literature indicates that some patients may benefit from a dosage of 140mg erenumab once monthly-especially those with difficult-to-treat disease and prior treatment failures. The evidence indicates that erenumab at 140mg has a numerically better efficacy than 70mg across a broad spectrum of migraine outcomes, including preventing progression to chronic migraine. Cumulative data from the literature support a therapeutic gain with an increase from erenumab 70 to 140mg and a rationale for initiating 140mg in selected patients.

Migraine History and Outcomes in Military Pilots and Flight Surgeons.

BACKGROUND: Migraine is a common disorder with significant aeromedical implications. The variability and unpredictable nature of occurrences hampers accurate assessment of future risk. This uncertainty results in a necessarily conservative approach to aeromedical recommendations, which unfortunately may lead to over-restrictive dispositions. Limited long-term follow up information is available on migraine outcomes in pilots, particularly assessing for impact of potential modifiable aggravating factors.Methods: This retrospective study reviewed 159 U.S. Air Force pilots with migraine who had been granted aeromedical waivers. As a comparison group, 44 U.S. Air Force flight surgeons with migraine who had been granted aeromedical waivers were reviewed.Results: Migraine with aura and isolated migraine aura without headache accounted for the majority of migraine subtypes in both male and female subjects. Self-identified triggering factors were identified by 62% of subjects. The most commonly reported triggers were dietary factors, sleep disturbances, stress, caffeine intake, and hormonal factors. Sleep disturbances, stress, hormonal factors, and ethanol triggers were more frequently noted in female subjects. Self-reported positive response to trigger factor modification was noted in 54% of subjects. Subjects reported an average of only 3 migraine attacks in the previous year. Long-term follow up indicated continued aeromedical waiver in 91% of subjects.Discussion: The majority of subjects had migraine with aura or isolated migraine aura. Significant salutary response to modification of commonly-reported triggering factors was noted. These findings can be incorporated into individualized aeromedically-compatible management strategies to clarify symptom impact on aviation safety, improve symptom control, and increase the possibility of safe return to fly recommendations.Hesselbrock RR, Haynes JT. Migraine history and outcomes in military pilots and flight surgeons. Aerosp Med Hum Perform. 2022; 93(1):26-31.

Erenumab following treatment discontinuation

Current national regulations request a three months discontinuation following a 12 months treatment cycle with monoclonal antibodies targeting CGRP. Aim of the present study was to assess migraine outcome following erenumab discontinuation and subsequent re-treatment.

CGRP monoclonal antibodies early onset of efficacy following four weeks of treatment in chronic migraine

Various studies have documented a rapid onset of efficacy in migraine prevention for monoclonal antibodies targeting CGRP. Aim of the present study was to assess migraine outcome following the first 4 weeks of treatment in patients treated with erenumab 70 mg or galcanezumab 240 mg (loading dose).

Onabotulinumtoxin-a during COVID-19 pandemic: Long-term efficacy in chronic migraine

Current guidelines recommend regulare quarterly administration of Onabotulinumtoxin-A in chronic migraine patients. During the first Italian COVID-19 related quarantine period, as per national and international guidelines, Onabotulinumtoxin-A administrations were suspended, given its biological risk. Aim of the present study was to assess migraine outcome in patients in prophylaxis with Onabotulinumtoxin-A during COVID-19 related treatment suspension (March-May 2020).

Galcanezumab effectiveness on comorbid cluster headache and chronic migraine: a prospective case series.

Cluster headache (CH) and migraine are recurrent painful primary cephalalgies, typically with different clinical appearance and some shared features, such as unilateral pain, common triggers and response to triptans and/or monoclonal antibodies against the calcitonin gene-related peptide (CGRP) pathway. Common pathophysiological mechanisms are proposed in CH and migraine, including the role of the trigeminal-vascular system with its most representative neuropeptide, CGRP. Very few case series have been conducted so far investigating anti-CGRP treatments in patients with comorbid CH and migraine, and no cases have been reported which assess both CH and chronic migraine outcomes. We describe 4 patients with both chronic migraine and cluster headache, with or without failure to preventive medications. Galcanezumab (240mg loading dose, followed by 120mg monthly) was used for at least a 3-month treatment, demonstrating improvement in both migraine and CH outcomes (i.e. migraine days, CH attacks, Headache Impact Test -6 item score, acute medications use), achieving sustained clinical benefit. No adverse events were reported. Taking into account the role of CGRP in migraine and CH pathophysiology, a usually well-tolerated treatment with CGRP blockade could be a rationale-based option to treat patients with coexisting chronic migraine and cluster headache. Additional studies are needed to assess the role of anti-CGRP drugs in episodic and chronic CH treatment, as well as to establish correct timing and patient prerequisites to begin therapy.

Efficacy and Safety of Migraine Surgery: A Systematic Review and Meta-analysis of Outcomes and Complication Rates.

The objectives of this study are to assess the efficacy and safety of peripheral nerve surgery for migraine headaches and to bibliometrically analyze all anatomical studies relevant to migraine surgery. Migraines rank as the second leading cause of disability worldwide. Despite the availability of conservative management options, individuals suffer from refractive migraines which are associated with poor quality of life. Migraine surgery, defined as the peripheral nerve decompression/trigger site deactivation, is a relatively novel treatment strategy for refractory migraines. EMBASE and the National Library of Medicine (PubMed) were systematically searched for relevant articles according to the PRISMA guidelines. Data was extracted from studies which met the inclusion criteria. Pooled analyses were performed to assess complication rates. Meta-analyses were run using the random effects model for overall effects and within subgroup fixed-effect models were used. A total of 68 studies (38 clinical, 30 anatomical) were included in this review. There was a significant overall reduction in migraine intensity (P < 0.001, SE = 0.22, I2 = 97.9), frequency (P < 0.001, SE = 0.17, I2 = 97.7), duration (P < 0.001, SE = 0.15, I2 = 97), and migraine headache index (MHI, P < 0.001, SE = 0.19, I2 = 97.2) at follow-up. A total of 35 studies reported on migraine improvement (range: 68.3%-100% of participants) and migraine elimination (range: 8.3%-86.5% of participants). 32.1% of participants in the clinical studies reported complications for which the most commonly reported complications being paresthesia and numbness, which was mostly transient, (12.11%) and itching (4.89%). This study demonstrates improved migraine outcomes and an overall decrease in MHI as well as strong evidence for the safety profile and complication rate of migraine surgery.

Outcomes of Migraine and Tension-Type Headache in Children and Adolescents.

The aim of our study was to evaluate the long-term outcomes of pediatric migraine and TTH in a clinical setting. We conducted a cohort study. Pediatric patients who visited the pediatric neurology clinic due to diagnoses of migraine or TTH were contacted by phone 8–10 years after their initial diagnosis and interviewed about their outcomes. Of 147 children, we were able to reach 120 (81%) patients. Of these 120 patients, 59 were seen initially due to migraine and 61 due to TTH. For the migraine patients, headaches improved in 48 (81.4%) and worsened in four (6.8%). Regarding diagnosis at follow-up, 59% still had migraine, 17% had TTH, and 23% were headache-free. Aura and photophobia were significantly associated with persistence of a migraine diagnosis. For the TTH patients, headaches improved in 49 (81.7%) and worsened in nine (15.0%). Regarding diagnosis at follow-up, 36.7% still had TTH, 18.3% had migraine, and 45% were headache-free. Of the patients with TTH, 36.7% retained their initial diagnosis compared to 59.3% among the migraine patients. Most pediatric patients presenting with migraine or TTH will experience a favorable outcome over 10 years, with TTH patients having twice the chance of complete resolution.

Erenumab Discontinuation After 12-Month Treatment

To assess migraine outcome after 12-month treatment with erenumab and compare patients who underwent 3-month erenumab discontinuation following the first treatment cycle with those who continued monthly administrations. This is a multicentric observational study in patients with migraine in treatment with erenumab. After a full 12-month treatment cycle (T12), patients could either continue or discontinue erenumab for at least 3 months. Patients who underwent treatment discontinuation were assessed after 3 months (T15) to decide whether to start retreatment. Patients were then assessed following at T16 and T18. Thirty consecutive patients were enrolled. Nineteen patients underwent treatment suspension at T12 up to T15, whereas 11 continued prophylaxis. At T15, patients who discontinued treatment documented significantly more migraine days (17.06 ± 6.5 vs 4.8 ± 2.5; p < 0.0001) and analgesics consumption (14.8 ± 9.2 vs 4.6 ± 2.5; p = 0.002), compared with those who continued treatment. After retreatment, at T16, patients who had previously undergone discontinuation documented a significant improvement in terms of migraine days (9.01 ± 4.4 vs 17.06 ± 6.5; p < 0.0001) and analgesics consumption (9.6 ± 7.3 vs 14.8 ± 9.2; p = 0.004). Such improvement was even greater at T18, comparable with T12. After treatment discontinuation, a rapid migraine worsening was found, despite the high clinical response during treatment and at retreatment, which might be secondary to an untimely interruption of a potentially disease-modifying pharmacologic intervention. Although clinical improvement was documented after retreatment, given the high frequency and degree of worsening during discontinuation, it seems plausible-even ethical-to re-evaluate current timing of discontinuation. This study provides Class III evidence that people with migraine discontinuing erenumab migraine prophylaxis after 12 months were more likely to have an increase in nonresponder status and migraine days than those who continued treatment.

Migraine and Mood in Children.

Migraine is one of the most prevalent headache disorders in children and negatively influences their quality of life. Physical, social, and school functioning are negatively affected. Mood changes are common in migraineurs and may happen before, during, or after a migraine headache. Children with migraine are not exempt from mood swings. The majority of mood changes occur during the prodromal phase, manifesting as a psychobiological response, e.g., difficulty thinking, trouble concentrating, irritability, higher or lower energy, confusion, and depression. A bi-directional relationship between migraine and mood has been proposed, but mechanisms are not clear. Collectively, a maladaptive stress response has been suggested to explain the inability to balance homoeostatic changes when facing various stressors. Recognizing mood changes and monitoring mood patterns in children with migraine, for example, by various apps and so-called mood monitors, is valuable for better management. A multidisciplinary intervention has been recommended to reduce migraine disability, improve coping strategies, and reduce chronification risks in children with migraine. Pharmacological and non-pharmacological strategies are both available and effective. Biofeedback, relaxation, and cognitive-behavioral therapy yield positive outcomes in pediatric migraine. Developing healthy lifestyle habits (diet, exercise, sleep) also seems to improve migraine in this population.

A systematic review and meta-analyses on the prevalence of pregnancy outcomes in migraine treated patients: a contribution from the IMI2 ConcePTION project.

The present study aims to summarize the safety profile of the medications used to treat migraine during pregnancy by performing a systematic review and meta-analyses. The term "migrain*" combined with pregnancy terms were used to search Embase, PubMed, PsychInfo, Scopus, and Web of Science through 31 December 2020. Pooled prevalences of untreated and treated migraine patients were estimated using MetaXL software. Pooled odds ratios (OR) using random effects models were estimated in RevMan 5. All the identified studies assessed medications used to treat acute migraine. The pooled prevalence of adverse pregnancy outcomes in patients prescribed any migraine medication ranged from 0.4% (95% CI 0.2-0.7%) for stillbirth to 12.0% (95%CI 7.8-16.9%) for spontaneous abortions. Among untreated patients with migraine, the pooled prevalence of the assessed pregnancy outcomes ranged from 0.6% (95% CI: 0-1.7%) for stillbirth to 10.4% (95% CI: 8.9-12%) for gestational age < 37weeks. Given the limited data, it was only possible to perform OR meta-analyses for triptans. The adjusted ORs for triptan users compared the general population were: for major malformations 1.07 (95%CI: 0.83-1.39, p = 0.60); birth weight < 2500g 1.18 (95%CI: 0.94-1.48, p = 0.16); gestational age < 37weeks 1.49 (95% CI: 0.37-6.08, p = 0.58). In conclusion, triptans do not appear to increase the risk of pregnancy outcomes when compared to the general population. It was not possible to assess other migraine medications. Further studies are needed to investigate the safety of individual medications of acute and prophylactic migraine treatment among pregnant women.

Barriers to care in episodic and chronic migraine: Results from the Chronic Migraine Epidemiology and Outcomes Study.

To assess rates of and factors associated with traversing fundamental barriers to good medical outcomes and pharmacologic care in individuals with episodic migraine (EM) and chronic migraine (CM), including socioeconomic status and race. Barriers to good outcomes in migraine include the lack of appropriate medical consultation, failure to receive an accurate diagnosis, not being offered a regimen with acute and preventive pharmacologic treatments (if indicated), and not avoiding medication overuse. The Chronic Migraine Epidemiology and Outcomes (CaMEO) Study was a longitudinal Internet-based survey. Respondents who met criteria for migraine consistent with the International Classification of Headache Disorders, 3rd edition, had a Migraine Disability Assessment score≥6, and provided health insurance coverage status were included in this analysis. Successfully traversing each barrier to care and the effects of sociodemographic characteristics were examined. Among 16,789 respondents with migraine, 9184 (54.7%; EM: 7930; CM: 1254) were eligible. Current headache consultation was reported by 27.6% (2187/7930) of EM and 40.8% (512/1254) of CM respondents. Among consulters, 75.7% (1655/2187) with EM and 32.8% (168/512) with CM were accurately diagnosed. Among diagnosed consulters, 59.9% (992/1655) with EM and 54.2% (91/168) with CM reported minimally appropriate acute and preventive pharmacologic treatment. Among diagnosed and treated consulters, in the EM group 31.8% (315/992) and in the CM group 74.7% (68/91) met medication overuse criteria. Only 8.5% (677/7930) of EM and 1.8% (23/1254) of CM respondents traversed all four barriers. Higher income was positively associated with likelihood of traversing each barrier. Blacks and/or African Americans had higher rates of consultation than other racial groups. Blacks and/or African Americans and multiracial people had higher rates of acute medication overuse. Efforts to improve care should focus on increasing consultation and diagnosis rates, improving the delivery of all appropriate guideline-based treatment, and avoidance of medication overuse.

Tracking Migraine Digitally: The Future of Migraine Management

ObjectiveThis study was conducted to understand the impact of tracking migraine via an app on patient-provider communication and migraine outcomes as well as patient perspectives of the app. MethodsData collected were (1) patient-reported via a smartphone app developed for tracking migraines and (2) provided by integrated delivery networks. ResultsResults contribute to the understanding that migraines place substantial physical and functional burden on people and highlight the role that tracking symptoms may play to improve migraine management. ConclusionsDigital tools, such as apps, aid in communication between patients and health care providers, possibly enhancing patient knowledge and understanding of their migraines and health care providers being able to better treat patients.

Different Chinese patent medicine therapies for migraine: A protocol for systematic review and network meta-analysis.

Background:Migraine is a clinically high incidence rate of neurovascular disease. It is a recurrent headache. It is characterized by nausea, vomiting, fear of voice, and photophobia. Nowadays, a large number of randomized controlled clinical studies have shown that Chinese patent medicine has the advantages of good curative effect and high safety in the treatment of migraine. However, due to the variety of proprietary Chinese medicines, their relative effectiveness and safety have not yet been verified. Therefore, this study will use the network meta-analysis method to verify the effectiveness and safety of different kinds of Chinese patent medicines in the treatment of migraine.Methods:All randomized controlled trials of Toutongning capsule, Yangxue Qingnao granule, naoxintong capsules, Tianmagouteng granules in the treatment of migraine were searched from PubMed, Cochrane Library, web of science, EMBASE, sinomed, CNKI, Wanfang database, VIP. The retrieval time is from the establishment of the database to November 18, 2020. In order to avoid omission, we will manually retrieve relevant references and conference papers. According to the inclusion and exclusion criteria, we evaluated the quality and risk of all the retrieved literatures. Methodological quality assessment and bias risk will be assessed using the Cochrane bias risk tool. Revman 5.3, WinBUGS 1.4.3, and stata14.2 software will be used for all data analysis.Results:This study will directly or indirectly compare the effectiveness of different interventions on migraine outcome indicators, and rank the effectiveness. The main outcome measures included total effective rate (total effective rate = rocovery + obvious effective + effective/total number of cases × 100%), visual analogue scale (VAS) score, and secondary outcome indicators included analgesic effect evaluation index and quality of life scale.Conclusion:To provide evidence for evidence-based medicine and clinical researchers to choose more effective Chinese patent medicines to treat migraine.

Characterization of opioidergic mechanisms related to the anti-migraine effect of vagus nerve stimulation

Vagus nerve stimulation (VNS) is a promising neuromodulation approach used in the treatment of migraine, whose therapeutic mechanism is largely unknown. Previous studies suggest that VNS's anti-nociceptive effects may, in part, involve engaging opioidergic mechanisms. We used a validated preclinical model of head pain, with good translational outcomes in migraine, acute intracranial-dural stimulation, which has responded to invasive VNS.We tested the effects of μ (MOR), δ (DOR) and κ (KOR) opioid receptor agonists in this model, and subsequently the effects of opioid receptor antagonists against VNS-mediated neuronal inhibition. MOR, DOR, and KOR agonists all inhibited dural-evoked trigeminocervical neuronal responses. Both DOR and KOR agonists also inhibited ongoing spontaneous firing of dural responsive neurons. Both DOR and KOR agonists were more efficacious than the MOR agonist in this model. We confirm the inhibitory effect of invasive VNS and demonstrate that this effect was prevented by a broad-spectrum opioid receptor antagonist, and by a highly selective DOR antagonist. Our data confirm the role of MOR in dural-trigeminovascular neurotransmission and additionally provide evidence of a role of both DOR and KOR in dural-nociceptive transmission of trigeminocervical neurons. Further, the results here provide evidence of engagement of opioidergic mechanisms in the therapeutic action of VNS in headache, specifically the DOR. These studies provide further support for the important role of the DOR in headache mechanisms, and as a potential therapeutic target. The data begin to dissect the mode of action of the analgesic effects of VNS in the treatment of primary headache disorders.

Early outcomes of migraine after erenumab discontinuation: data from a real-life setting.

Monoclonal antibodies targeting the calcitonin gene-related peptide, including erenumab, are migraine-specific preventive treatments, whose long-term effectiveness has still to be evaluated in real-life settings. We assessed early outcomes of erenumab discontinuation after a 52-week treatment in patients with a continuous positive response to the drug. We evaluated the early outcomes after treatment completion in migraineurs from a real-life multicenter register. All patients received monthly erenumab for 52weeks and attended a 8-week follow-up after treatment completion. Primary outcomes were responder rates and changes in monthly migraine days (MMDs), acute medications days (AMDs), and pain intensity on a Numerical Rating Scale (NRS score) during weeks 1-4 after erenumab treatment completion. The 32 included patients reported a decrease in MMDs, AMDs, and NRS score during the last 4weeks of treatment compared with baseline (P<0.001). During weeks 1-4 after treatment completion, all the outcome measures increased compared with the last 4weeks of treatment (P < 0.001) despite staying lower than baseline (MMDs and AMDs P < 0.001, NRS score P = 0.005). Over the same time frame, 18 (56%) patients maintained a ≥ 50% reduction from baseline in MMDs. At week 4 after treatment completion, 10 (31%) patients restarted treatment due to disease rebound to baseline levels. More than half patients had an early disease worsening, while the remaining patients maintained their responder status during weeks 1-4 after treatment completion. Further studies might identify predictors of prolonged response to erenumab and define the optimal treatment duration according to patients' characteristics.