Multimodal digital health treatments for Chronic Migraine associated with Medication Overuse Headache: a literature appraisal and results of a single-arm open trial (the BE-HOME program).

BACKGROUND: Mindfulness-based treatments gained popularity for migraine treatment. In this manuscript we report the results of a single-arm open pilot study that evaluated the impact of a multimodal web-based intervention combining home-based medication withdrawal, patients' education, and online mindfulness-based interventions. We aimed to address whether our program had the ability to show a change in the observed parameters and the study should therefore be intended as an early phase trial. METHODS: Consecutive patients with chronic migraine associated with medication overuse headache were enrolled, followed-up for 12 months, in a program that included home-based medication withdrawal, education on the correct use of drugs and lifestyle issues, prescription of tailored pharmacological prophylaxis, and attendance to six online mindfulness-based sessions. We tested the effect of the program on improving headache frequency, medication intake, quality of life (QoL), headache impact, depression, self-efficacy, and pain catastrophizing. RESULTS: A total of 37 patients completed the study (10 dropped out). We observed a large improvement in headache frequency, medication intake, headache impact, and QoL, a moderate improvement in pain catastrophizing and a mild improvement in depression symptoms; 70% to 76% of patients achieved 50% or more reduction in headache frequency from baseline to each follow-up (p < .01). CONCLUSIONS: The results of our multimodal program showed significant improvements in headache frequency, medication intake, and patient-reported outcomes. Future studies are needed to better identify patients who might benefit most from Digital Health Interventions and to demonstrate at least an equivalence in outcome with in-person programs carried out in hospital settings.

Gender-related stress factors and emotional perception in migraine: a structured online questionnaire in migraine patients and controls.

BACKGROUND: While migraine is markedly prevalent in women, gender-related phenotype differences were rarely assessed. For this reason, we investigated, through a multicenter observational cross-sectional study, based on an online questionnaire, gender-related differences in stress factors, emotions, and pain perception in migraine patients and controls and their impact on migraine severity. METHODS: The study was designed as an online questionnaire. The link was emailed to healthy subjects (C) and migraine patients (MIG) (age 18-75, education ≥ 13 years) recruited during the first visit in 8 Italian Headache Centers adhering to Italian Society for Headache Study (SISC). The questionnaire included personal/social/work information, the Perceived Stress Scale, the Romance Quality Scale, the Emotion Regulation Questionnaire, the Beck Anxiety Inventory, the Body Perception Questionnaire, the pain perception, and a self-assessment of migraine severity in the last 3 months. RESULTS: 202 MIG and 202 C completed the survey. Independently from gender, migraine was characterized by higher pain sensitivity and more severe partner relationships. The female gender, in MIG, exhibited higher anxiety scores, body awareness, and reduced emotional suppression. Body awareness and emotional suppression were discriminating factors between genders in control and migraine groups without relevant influence on disease features. Perceived perception of migraine severity was similar between genders. CONCLUSION: Gender-related emotional and stress factors did not contribute to delineate a distinct phenotype in migraine men and women. The possible impact of emotional and stress factors characterizing genders could be considered for a single case-tailored therapeutic approach.

Real-world effectiveness of Anti-CGRP monoclonal antibodies compared to OnabotulinumtoxinA (RAMO) in chronic migraine: a retrospective, observational, multicenter, cohort study.

BACKGROUND: Chronic migraine (CM) is a disabling condition with high prevalence in the general population. Until the recent approval of monoclonal antibodies targeting the calcitonin gene-related peptide (Anti-CGRP mAbs), OnabotulinumtoxinA (BoNT-A) was the only treatment specifically approved for CM prophylaxis. Direct comparisons between the two treatments are not available so far. METHODS: We performed an observational, retrospective, multicenter study in Italy to compare the real-world effectiveness of Anti-CGRP mAbs and BoNT-A. Patients with CM who had received either treatment according to Italian prescribing regulations were extracted from available clinical databases. Efficacy outcomes included the change from baseline in monthly headache days (MHD), MIgraine Disability ASsessment test (MIDAS), and monthly acute medications (MAM) evaluated at 6 and 12 months of follow-up. The primary outcome was MHD change from baseline at 12 months. Safety outcomes included serious adverse events (SAE) and treatment discontinuation. Unadjusted and adjusted models were used for the analyses. RESULTS: Two hundred sixteen potentially eligible patients were screened; 183 (86 Anti-CGRP mAbs; 97 BoNT-A) were included. One hundred seventy-one (80 Anti-CGRP mAbs; 91 BoNT-A) and 154 (69 Anti-CGRP mAbs; 85 BoNT-A) patients were included in the efficacy analysis at 6 and 12 months of follow-up, respectively. Anti-CGRP mAbs and BoNT-A both resulted in a mean MHD reduction at 6 (-11.5 and -7.2 days, respectively; unadjusted mean difference -4.3; 95%CI -6.6 to -2.0; p = 0.0003) and 12 months (-11.9 and -7.6, respectively; unadjusted mean difference -4.4; 95%CI -6.8 to -2.0; p = 0.0002) of follow-up. Similar results were observed after adjusting for baseline confounders. Anti-CGRP mAbs showed a significant MIDAS (-31.7 and -19.2 points, p = 0.0001 and p = 0.0296, respectively) and MAM reduction (-5.1 and -3.1 administrations, p = 0.0023 and p = 0.0574, respectively) compared to BoNT-A at 6 and 12 months. No SAEs were reported. One patient receiving fremanezumab discontinued treatment due to arthralgia. Treatment discontinuations, mainly for inefficacy, were comparable. CONCLUSION: Both Anti-CGRP mAbs and BoNT-A were effective in CM patients with Anti-CGRP mAbs presenting higher effect magnitude, with comparable safety. Still, BoNT-A remains a valuable option for CM patients with contraindications to Anti-CGRP mAbs or for frail categories who are candidates to local therapy with limited risk of systemic administration.

Longitudinal neurofunctional changes in medication overuse headache patients after mindfulness practice in a randomized controlled trial (the MIND-CM study).

BACKGROUND: Mindfulness practice has gained interest in the management of Chronic Migraine associated with Medication Overuse Headache (CM-MOH). Mindfulness is characterized by present-moment self-awareness and relies on attention control and emotion regulation, improving headache-related pain management. Mindfulness modulates the Default Mode Network (DMN), Salience Network (SN), and Fronto-Parietal Network (FPN) functional connectivity. However, the neural mechanisms underlying headache-related pain management with mindfulness are still unclear. In this study, we tested neurofunctional changes after mindfulness practice added to pharmacological treatment as usual in CM-MOH patients. METHODS: The present study is a longitudinal phase-III single-blind Randomized Controlled Trial (MIND-CM study; NCT03671681). Patients had a diagnosis of CM-MOH, no history of neurological and severe psychiatric comorbidities, and were attending our specialty headache centre. Patients were divided in Treatment as Usual (TaU) and mindfulness added to TaU (TaU + MIND) groups. Patients underwent a neuroimaging and clinical assessment before the treatment and after one year. Longitudinal comparisons of DMN, SN, and FPN connectivity were performed between groups and correlated with clinical changes. Vertex-wise analysis was performed to assess cortical thickness changes. RESULTS: 177 CM-MOH patients were randomized to either TaU group or TaU + MIND group. Thirty-four patients, divided in 17 TaU and 17 TaU + MIND, completed the neuroimaging follow-up. At the follow-up, both groups showed an improvement in most clinical variables, whereas only TaU + MIND patients showed a significant headache frequency reduction (p = 0.028). After one year, TaU + MIND patients showed greater SN functional connectivity with the left posterior insula (p-FWE = 0.007) and sensorimotor cortex (p-FWE = 0.026). In TaU + MIND patients only, greater SN-insular connectivity was associated with improved depression scores (r = -0.51, p = 0.038). A longitudinal increase in cortical thickness was observed in the insular cluster in these patients (p = 0.015). Increased anterior cingulate cortex thickness was also reported in TaU + MIND group (p-FWE = 0.02). CONCLUSIONS: Increased SN-insular connectivity might modulate chronic pain perception and the management of negative emotions. Enhanced SN-sensorimotor connectivity could reflect improved body-awareness of painful sensations. Expanded cingulate cortex thickness might sustain improved cognitive processing of nociceptive information. Our findings unveil the therapeutic potential of mindfulness and the underlying neural mechanisms in CM-MOH patients. TRIAL REGISTRATION: Name of Registry; MIND-CM study; Registration Number ClinicalTrials.gov identifier: NCT0367168; Registration Date: 14/09/2018.

The World Health Organization Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders and the headache revolution: from headache burden to a global action plan for headache disorders.

The World Health Organization (WHO) Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders was developed by WHO to address the worldwide challenges and gaps in provision of care and services for people with epilepsy and other neurological disorders and to ensure a comprehensive, coordinated response across sectors to the burden of neurologic diseases and to promote brain health across life-course. Headache disorders constitute the second most burdensome of all neurological diseases after stroke, but the first if young and midlife adults are taken into account. Despite the availability of a range of treatments, disability associated with headache disorders, and with migraine, remains very high. In addition, there are inequalities between high-income and low and middle income countries in access to medical care. In line with several brain health initiatives following the WHOiGAP resolution, herein we tailor the main pillars of the action plan to headache disorders: (1) raising policy prioritization and strengthen governance; (2) providing effective, timely and responsive diagnosis, treatment and care; (3) implementing strategies for promotion and prevention; (4) fostering research and innovation and strengthen information systems. Specific targets for future policy actions are proposed. The Global Action Plan triggered a revolution in neurology, not only by increasing public awareness of brain disorders and brain health but also by boosting the number of neurologists in training, raising research funding and making neurology a public health priority for policy makers. Reducing the burden of headache disorders will not only improve the quality of life and wellbeing of people with headache but also reduce the burden of neurological disorders increasing global brain health and, thus, global population health.

Different personality profiles in patients with cluster headache: a data-driven approach.

INTRODUCTION: Cluster headache (CH) is usually comorbid to mood spectrum disorders, but the psychopathological aspects are poorly explored. We aimed at identifying discrete profiles of personality traits and their association with clinical features. METHODS: Based on the personality scales of the Millon Clinical Multiaxial Inventory-III, principal component analysis (PCA) identified psychological patterns of functioning of 56 CH patients. PCA outcomes were used for hierarchical cluster analysis (HCA) for sub-groups classification. RESULTS: Eighty-seven percent of patients had personality dysfunctions. PCA found two bipolar patterns: (i) negativistic, sadic-aggressive, borderline, and compulsive traits were distinctive of the psychological dysregulation (PD) dimension, and (ii) narcissistic, histrionic, avoidant, and schizoid traits loaded under the social engagement (SE) component. PD was associated with disease duration and psychopathology. SE was related to educational level and young age. HCA found three groups of patients, and the one with high PD and low SE had the worst psychological profile. CONCLUSIONS: Personality disorders are common in CH. Our data-driven approach revealed distinct personality patterns which can appear differently among patients. The worst combination arguing against mental health is low SE and high PD. Linking this information with medical history may help clinicians to identify tailored-based therapeutic interventions for CH patients.

Efficacy of mindfulness added to treatment as usual in patients with chronic migraine and medication overuse headache: a phase-III single-blind randomized-controlled trial (the MIND-CM study).

BACKGROUND: Mindfulness gained considerable attention for migraine management, but RCTs are lacking. We aimed to assess the efficacy of a six-sessions mindfulness-based treatment added to treatment as usual (TaU) in patients with Chronic Migraine (CM) and Medication Overuse Headache (MOH) on headache frequency, medication intake, quality of life, disability, depression and anxiety, cutaneous allodynia, awareness of inner states, work-related difficulties, and disease cost. METHODS: In this Phase-III single-blind RCT carried out in a specialty Italian headache center, 177 patients with CM and MOH were randomized 1:1 to either TaU (withdrawal from overused drugs, education on proper medication use and lifestyle issues, and tailored prophylaxis) or mindfulness-based intervention added to TaU (TaU + MIND). The mindfulness-based intervention consisted of six group session of mindfulness practice and 7-10 min daily self-practice. The primary endpoint was the achievement of ≥ 50% headache frequency reduction at 12 months compared to baseline, and was analyzed on an intention-to-treat principle using Pearson's Chi-Squared test. Secondary endpoints included medication intake, quality of life (QoL), disability, depression and anxiety, cutaneous allodynia, awareness of inner states, work-related difficulties, and disease cost. The secondary endpoints were analyzed using per-protocol linear mixed models. RESULTS: Out of the 177 participants 89 were randomized to TaU and 88 to TaU + MIND. Patients in the TaU + MIND group outperformed those in TaU for the primary endpoint (78.4% vs. 48.3%; p < 0.0001), and showed superior improvement in headache frequency, QoL and disability, headache impact, loss of productive time, medication intake, and in total, indirect and direct healthcare costs. CONCLUSIONS: A mindfulness-based treatment composed of six-week session and 7-10 min daily self-practice added on to TaU is superior to TaU alone for the treatment of patients with CM and MOH. TRIAL REGISTRATION: MIND-CM was registered on clinicaltrials.gov (NCT03671681) on14/09/2018.

Rethinking headache as a global public health case model for reaching the SDG 3 HEALTH by 2030.

The 2030 Agenda for Sustainable Development sets out, through 17 Sustainable Development Goals (SDGs), a path for the prosperity of people and the planet. SDG 3 in particular aims to ensure healthy lives and promote well-being for all at all ages and includes several targets to enhance health. This review presents a "headache-tailored" perspective on how to achieve SDG 3 by focusing on six specific actions: targeting chronic headaches; reducing the overuse of acute pain-relieving medications; promoting the education of healthcare professionals; granting access to medication in low- and middle-income countries (LMIC); implementing training and educational opportunities for healthcare professionals in low and middle income countries; building a global alliance against headache disorders. Addressing the burden of headache disorders directly impacts on populations' health, as well as on the possibility to improve the productivity of people aged below 50, women in particular. Our analysis pointed out several elements, and included: moving forward from frequency-based parameters to define headache severity; recognizing and managing comorbid diseases and risk factors; implementing a disease management multi-modal management model that incorporates pharmacological and non-pharmacological treatments; early recognizing and managing the overuse of acute pain-relieving medications; promoting undergraduate, postgraduate, and continuing medical education of healthcare professionals with specific training on headache; and promoting a culture that favors the recognition of headaches as diseases with a neurobiological basis, where this is not yet recognized. Making headache care more sustainable is an achievable objective, which will require multi-stakeholder collaborations across all sectors of society, both health-related and not health-related. Robust investments will be needed; however, considering the high prevalence of headache disorders and the associated disability, these investments will surely improve multiple health outcomes and lift development and well-being globally.

Mindfulness and other behavioral approaches.

Mindfulness and other behavioral approaches have demonstrated efficacy in treatment of different kinds of chronic pain condition and migraine in particular. Such treatments are of particular utility in the treatment of chronic forms of migraine, also associated to medication overuse headache, in reason of the relevant comorbidity - and bidirectional relationship - between migraine, and two of the most common associated conditions, namely anxiety and depression. Second, in reason of the impact that such treatments may have on behavioral issues that might promote MOH maintenance, including external locus of control and self-efficacy. Although the specific mechanism of action of these approaches has not been clarified yet, the absence of side effects and their effectiveness make these options suitable for different categories of frail patients and also for patients during therapy with medication if we want to improve the efficacy of medications itself. The use of these approaches has to be encouraged for clinicians and for patients to treat at the best pain condition and migraine and to improve the efficacy of the new medication for migraine prevention.

Management of chronic migraine with medication overuse by web-based behavioral program during the COVID-19 emergency: results at 12 months.

BACKGROUND: The study had been initiated because of restrictions put in place to control the spread of coronavirus in Milan in March 2020 that impacted clinical activities at our tertiary headache center in Milan (Foundation IRCSS Carlo Besta Neurological Institute). Treatment efforts were modified to make use of telephonic and internet communication to maintain care of our patients. METHODS: Nineteen patients had undergone our withdrawal protocol for medication overuse headache and were scheduled for follow-up that included pharmacological prophylaxis combined with behavioral therapy and mindfulness, generally performed in small group face-to-face sessions. A behavioral program was organized for them by technology modality (smartphone) due to the pandemic restrictions. RESULTS: The results concern 12-month follow-up. The clinical indexes showed migraine days per month 20.6 (± 6) pre vs 11.2 (± 3.1 at 12 months); medications intake per month 19.4 (± 5.8) pre vs 9.0 (± 4.6) at 12 months; MIDAS 67.7 (± 52.6) pre vs 71.1 (± 60) at 12 months; HIT-6 66.2 (± 5.3) pre vs 62.2 (± 5.9). CONCLUSION: The present study confirmed literature data, supporting the behavioral approach combined to traditional therapies as a novel method to follow patients and guarantee their benefit, also when applied using technology by telemedicine or smartphone.

Feasibility and effect of mindfulness approach by web for chronic migraine and high-frequency episodic migraine without aura at in adolescents during and after COVID emergency: preliminary findings.

BACKGROUND: Migraine disorders are common among adolescents: however, the efficacy of medical prophylaxis is limited in this population. This study reports preliminary findings on the feasibility and effect of a mindfulness-based intervention delivered via web for adolescents with chronic migraine (CM) and high-frequency episodic migraine (HFEM) without aura. METHODS: Patients with CM or HFEM received six session of a mindfulness-based treatment and were followed-up for 6 months as part of a larger study. Repeated measure analyses were carried out to test the effect of this behavioral intervention. RESULTS: A total of 12 patients were included in this analysis. A significant improvement was observed up to 6 months for headache frequency, symptoms of depression, and catastrophizing, and up to 3 months for patients' disability. No change was detected for patients' anxiety level. CONCLUSIONS: The results of our study provides initial support to the hypothesis that patients' education and mindfulness-based programs can be very useful in populations of adolescents with CM or HFEM.

Addressing the cost of chronic and episodic migraine and its main drivers: a short-term longitudinal analysis from a third-level Italian center.

BACKGROUND: Chronic migraine (CM) is one of the most disabling neurological diseases, often associated to medication overuse headache (MOH). These patients make high use of pharmacological and non-pharmacological treatments, and experience high work-related indirect costs. The aim of this study was to address and compare the main driver of cost associated to CM-MOH and EM, and to evaluate the effect of improvement in migraine profile on disease cost. METHODS: We selected patients with baseline CM-MOH who reverted to an episodic pattern by 3 months after structured withdrawal. Paired sample t-test was used to explore the variation in headache frequency and its costs. Regression models were run to address the impact of single cost categories on total migraine cost. RESULTS: A total of 261 patients were included. Significant reductions in headache frequency and its costs were observed, with the exception of medical prophylaxis cost. The cost of migraine from chronic to episodic pattern is reduced by 533€ per month and 80% of this reduction is accountable to reduced indirect costs, i.e., loss of productive time. CONCLUSIONS: The results of our study open to future considerations on future approaches to the treatment of CM-MOH in which new migraine-specific treatments, i.e., monoclonal antibodies, should be combined with other pharmacological and non-pharmacological ones.

Applying a biopsychosocial model to migraine: rationale and clinical implications.

Migraine is a complex condition in which genetic predisposition interacts with other biological and environmental factors determining its course. A hyperresponsive brain cortex, peripheral and central alterations in pain processing, and comorbidities play a role from an individual biological standpoint. Besides, dysfunctional psychological mechanisms, social and lifestyle factors may intervene and impact on the clinical phenotype of the disease, promote its transformation from episodic into chronic migraine and may increase migraine-related disability.Thus, given the multifactorial origin of the condition, the application of a biopsychosocial approach in the management of migraine could favor therapeutic success. While in chronic pain conditions the biopsychosocial approach is already a mainstay of treatment, in migraine the biomedical approach is still dominant. It is instead advisable to carefully consider the individual with migraine as a whole, in order to plan a tailored treatment. In this review, we first reported an analytical and critical discussion of the biological, psychological, and social factors involved in migraine. Then, we addressed the management implications of the application of a biopsychosocial model discussing how the integration between non-pharmacological management and conventional biomedical treatment may provide advantages to migraine care.

Acceptance and commitment therapy for high frequency episodic migraine without aura: Findings from a randomized pilot investigation.

OBJECTIVE: We compared the incremental effects of adding acceptance and commitment therapy (ACT) to pharmacological treatment as usual (TAU) in a sample of patients with high frequency episodic migraine without aura (HFEM), assessing impact on a spectrum of measures across multiple domains. BACKGROUND: Patients with HFEM are at risk of developing chronic migraine and medication overuse headache. ACT has been shown to be effective for the treatment of various chronic pain conditions, but little attention has been given to its therapeutic value in the management of recurring headaches. METHODS: In this single-blind (masking for outcome assessor), open-label, randomized clinical trial, 35 patients with HFEM, with a monthly headache frequency ranging from 9 to 14 days, were recruited at the headache center of C. Besta Neurological Institute and randomized to either TAU (patient education and pharmacological prophylaxis; n = 17) or TAU + ACT (n = 18). Patients assigned to the combined treatment arm additionally received six 90-min weekly group sessions of ACT therapy and two supplementary "booster" sessions. All patients were on a stable course of prophylactic medication in the 3 months prior to initiating either treatment. Monthly headache frequency served as the primary outcome measure, with all other data collected being considered as secondary measures (medication intake, disability, headache impact, anxiety and depression, catastrophizing, allodynia, cognitive inflexibility, pain acceptance, mindful attention and awareness). RESULTS: A total of 35 patients were enrolled: 17 randomized to TAU, of whom three dropped out, and 18 to TAU + ACT (no dropouts in this group). Headache frequency and medication intake decreased in both groups over 12 months, with patients in the TAU + ACT group showing statistically significant reduction earlier, that is, by month 3. Headache frequency was reduced by 3.3 days (95% CI: 1.4 to 5.2) among those randomized to ACT + TAU, whereas it increased by 0.7 days (95% CI: -2.7 to 1.3) among those randomized to TAU only (p = 0.007, partial η2  = 0.21), the difference being 4 days (95% CI: 1.2 to 6.8). Medication intake was reduced by 4.1 intakes (95% CI: 2.0 to 6.3) among those randomized to ACT + TAU and by 0.4 intakes (95% CI: -1.8 to 2.5) among those randomized to TAU only (p = 0.016; partial η2  = 0.17), the difference being 3.8 intakes (95% CI: 0.7 to 6.8). At 6 and 12 months, the variations were not different between the two groups for headache frequency and medication intake. The opposite was found for measures of headache impact and pain acceptance, where the differences over time favored patients allocated to TAU. Both groups improved with regard to measures of disability, anxiety and depression, catastrophizing, and cognitive inflexibility, whereas measures of allodynia and pain acceptance were stable over time. CONCLUSIONS: Our preliminary findings indicate that supplementing TAU with ACT can enhance the main clinical outcomes, namely headache frequency and medication intake of patients with HFEM.

Clinical features, disease progression, and use of healthcare resources in a large sample of 866 patients from 24 headache centers: A real-life perspective from the Italian chROnic migraiNe (IRON) project.

OBJECTIVE: To develop a dedicated Italian chronic migraine (CM) database (IRON project) to overcome disease misconceptions, improve clinical administration, reduce patients' burden, and rationalize economic resource allotment. BACKGROUND: Proper CM management requires a comprehensive appraisal of its full clinical, social, and economic complexity. METHODS: In this cross-sectional study, CM patients were screened in 24 certified headache centers with face-to-face interviews. Information on sociodemographic factors, medical history, characteristics of CM, and of prior episodic migraine (EM), and healthcare resource use was gathered using a semistructured web-based questionnaire. RESULTS: A total of 866 CM patients were enrolled. CM started ~20 years after EM onset (age at EM onset 17.4 ± 9.1 vs. age at CM onset 35.3 ± 12.5 [mean ± SD]). CM prophylaxis, used by 430/866 (49.6%) of the patients, was often ineffective, not tolerated, and prematurely discontinued. Medications and diagnostic workup, frequently inappropriate, were mostly subsidized by the Italian national health service. CM patients with ≥25 headache days/month revealed substantial clinical differences and heavier disability and economic burden compared with those with <25 headache days/month. CONCLUSIONS: CM is a heterogeneous headache disorder deserving more in-depth clinical characterization, sharper diagnostic criteria, and tailored treatments. CM registries are expected to improve clinical management, resulting in increased disease awareness, better healthcare resource allocation, and reduced economic burden.

Erenumab in the prevention of high-frequency episodic and chronic migraine: Erenumab in Real Life in Italy (EARLY), the first Italian multicenter, prospective real-life study.

OBJECTIVE: To assess the effectiveness, safety, and tolerability of erenumab in a real-life migraine population, while trying to identify responsiveness predictors. BACKGROUND: Erenumab is a fully human Ig-2 monoclonal antibody blocking the calcitonin gene-related peptide receptor, indicated for migraine prophylaxis. Phase II and III trials demonstrated that erenumab is effective, safe, and well tolerated in the prevention of episodic and chronic migraine (CM), showing an early onset of action. METHODS: This is a multicenter, prospective, cohort, and real-life study. We considered for enrolment all consecutive patients aged 18-65 affected by high-frequency episodic migraine (HFEM) or CM, with or without medication overuse, visited at nine Italian Headache Centers from December 20, 2018 to September 30, 2019. Each patient was treated with erenumab 70 mg, administered subcutaneously every 4 weeks. Treatment duration was planned to last from 6 to 12 months, depending on the patient's response. The primary endpoint was the change in monthly migraine days (MMDs) at weeks 9-12 compared to baseline. Secondary endpoints included changes in monthly analgesics intake, ≥50%, ≥75%, and 100% responder rates and any variation in the Visual Analog Scale (VAS) and Headache Impact Test scores (HIT). RESULTS: In total, 372 migraine patients were treated with at least one dose of erenumab 70 mg. At weeks 9-12, erenumab decreased MMDs by 4.5 ± 4.1 days (mean ± SD) in patients with HFEM and by 9.3 ± 9.1 (mean ± SD) days in those with CM compared to baseline. At weeks 9-12 VAS score was reduced by 1.9 ± 1.9 (mean ± SD), HIT score by 10.7 ± 8.8 (mean ± SD), and median monthly analgesics intake passed from 12.0 (interquartile range [IQR] 10.0-14.0) to 5.0 (IQR 3.0-7.0) in HFEM. In CM patients, VAS was reduced by 1.7 ± 2.0 (mean ± SD), HIT by 9.7 ± 10.4 (mean ± SD), and median monthly analgesics intake passed from 20.0 (IQR 15.0-30.0) to 8.0 (IQR 5.0-15.0). At week 12, ≥50% responders were 60/101 (59.4%) for HFEM and 146/263 (55.5%) for CM, ≥75% responders were 17/101 (16.8%) and 59/263 (22.4%) and 100% responders 1/101 (1.0%) and 3/263 (1.1%), respectively. Erenumab responsiveness in HFEM was positively associated with unilateral pain localization (OR: 3.03, 95% CI: 1.24-7.40; p = 0.015), whereas in CM responsiveness was positively associated with and baseline migraine frequency (OR: 1.06, 95% CI:1.02-1.11; p = 0.031), dopaminergic symptoms (OR: 2.01, 95% CI: 1.14-3.52; p = 0.015), and negatively associated with psychiatric comorbidities (OR: 0.43, 95% CI: 0.20-0.93; p = 0.003). CONCLUSIONS: Erenumab 70 mg is effective, safe, and well tolerated in real life. Easily obtainable clinical features might be of help in predicting patient's responsiveness.

Withdrawal failure in patients with chronic migraine and medication overuse headache.

OBJECTIVES: The management of chronic migraine (CM) with Medication Overuse Headache (MOH) consists of withdrawal therapy, education on medications' use and prescription of prophylaxis. Little attention has been given to patients who fail in achieving a successful short-term outcome after withdrawal: we aim to describe predictors of failure. METHODS: Patients with CM and MOH were enrolled at the Neurological Institute C. Besta of Milano, and included if they completed the three months follow-up. Withdrawal failure was defined as the situation in which patients either did not revert from chronic to episodic migraine (EM), were still overusing acute medications, or both did not revert to EM and kept overusing acute medications. Predictors of failure were addressed with a logistic regression, and for all variables, the longitudinal course in the two groups was described. RESULTS: In 39, out of 137 patients, withdrawal was unsuccessful: the predictors included day-hospital-based withdrawal (OR: 2.37; 95% CI: 1.06-5.29), emergency room (ER) access before withdrawal (OR: 2.81; 95% CI: 1.13-6.94) and baseline headache frequency >69 days/three months (OR: 2.97; 95% CI: 1.32-6.65). Patients who failed withdrawal did not improve on medications intake, use of prophylactic and non-pharmacological treatments, symptoms of anxiety and depression. CONCLUSIONS: Patients who were treated in day-hospital, those who recently attended ER for headache, and those with more than 69 headache/3 months, as well as to those with relevant symptoms of anxiety and depression who did not improve should be closely monitored to reduce likelihood of non-improvement after structured withdrawal.

Life with chronic pain during COVID-19 lockdown: the case of patients with small fibre neuropathy and chronic migraine.

OBJECTIVE: We aimed at investigating the impact of COVID-19-related distress on patients with chronic pain, highlighting the effects of changes in individual habits and public health care reconfiguration on physical and psychological health. METHODS: During the pandemic, 80 participants (25 patients with small fibre neuropathy (SFN), 42 patients with chronic migraine (CM) and 13 patients' healthy family members (HFM)) were asked to evaluate their COVID-19 complains, changes in habits and clinical management, behaviour, mood, loneliness, quality of life (QoL), physical and mental health and coping strategies. Data were analysed by Spearman rho correlations and Mann-Whitney U tests. RESULTS: Patients had lower QoL, lower physical health and higher catastrophizing attitude towards pain than HFM. During the pandemic, SFN patients referred greater decline in clinical symptoms, worries about contagion and discomfort for disease management changes than CM patients. In the SFN group, the higher levels of disability were associated with suffering from changes in neurologist-patient relationship. CM patients complained of agitation/anxiety that was related to feelings of loneliness, depressive mood and catastrophism. DISCUSSION: Despite similar complains of change in habits and worries about COVID-19 pandemic, SFN and CM patients had distinct reactions. In SFN patients, pandemic distress impacted on physical health with worsening of clinical conditions, especially suffering from changes in their care. In CM patients, pandemic distress affected behaviour, mainly with psychological frailty. This suggests the need to customize public health care for patients with distinct chronic pain conditions.

Narrative Medicine to integrate patients', caregivers' and clinicians' migraine experiences: the DRONE multicentre project.

BACKGROUND: Although migraine is widespread and disabling, stigmatisation and poor awareness of the condition still represent barriers to effective care; furthermore, research on migraine individual and social impact must be enhanced to unveil neglected issues, such as caregiving burden. The project investigated the migraine illness experience through Narrative Medicine (NM) to understand daily life, needs and personal resources of migraneurs, their caregivers and clinicians, and to provide insights for clinical practice. METHODS: The project involved 13 Italian headache centres and targeted migraneurs, their caregivers and migraine specialists at these centres. Written narratives, composed by a sociodemographic survey and illness plot or parallel chart, were collected through the project's webpage. Illness plots and parallel charts employed open words to encourage participants' expression. Narratives were analysed through Nvivo software, interpretive coding and NM classifications. RESULTS: One hundred and seven narratives were collected from patients and 26 from caregivers, as well as 45 parallel charts from clinicians. The analysis revealed migraine perception in social, domestic and work life within the care pathway evolution and a bond between chaos narratives and day loss due to migraine; furthermore, narratives suggested the extent of the caregiving burden and a risk of underestimation of migraine burden in patients' and caregivers' life. CONCLUSION: The project represents the first investigation on migraine illness experience through NM simultaneously considering migraneurs', caregivers' and clinicians' perspectives. Comparing narratives and parallel charts allowed to obtain suggestions for clinical practice, while NM emerged as able to foster the pursuing of migraine knowledge and awareness.

Neuro-telehealth for fragile patients in a tertiary referral neurological institute during the COVID-19 pandemic in Milan, Lombardy.

BACKGROUND: Lombardy was severely hit by the COVID-19 pandemic since February 2020 and the Health System underwent rapid reorganization. Outpatient clinics were stopped for non-urgent patients: it became a priority to manage hundreds of fragile neurological patients who suddenly had less reference points. In Italy, before the pandemic, Televisits were neither recognized nor priced. METHODS: At the Fondazione IRCCS Istituto Neurologico C. Besta, we reorganized outpatient clinics to deliver Neuro-telemedicine services, including Televisits and Teleneurorehabilitation, since March 2020. A dedicated Working Group prepared the procedure, tested the system, and designed satisfaction questionnaires for adults and children. RESULTS: After a pilot phase, we prepared a procedure for Telemedicine outpatient clinics which was approved by hospital directions. It included prescription, booking, consenting, privacy and data protection, secure connection with patients (Teams Microsoft 365), electronic report preparation and delivery, reporting, and accountability of the services. During the March-September 2020 period, we delivered 3167 Telemedicine services, including 1618 Televisits, to 1694 patients (972 adults, 722 children) with a wide range of chronic neurological disorders. We successfully administered different clinical assessment and scales. Satisfaction among patients and caregivers was very high. CONCLUSIONS: During the dramatic emergency, we were able to take care of more than 1600 patients by organizing Neuro-telehealth in a few weeks, lessening the impact of the pandemic on fragile patients with chronic neurological disorders; this strategy is now stably embedded in our care pathways. In Italy, Telehealth is at present recognized and priced and is becoming a stable pillar of the health system.