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.

The EMPOWER Occupational e-Mental Health Intervention Implementation Checklist to Foster e-Mental Health Interventions in the Workplace: Development Study.

BACKGROUND: Occupational e-mental health (OeMH) interventions significantly reduce the burden of mental health conditions. The successful implementation of OeMH interventions is influenced by many implementation strategies, barriers, and facilitators across contexts, which, however, are not systematically tracked. One of the reasons is that international consensus on documenting and reporting the implementation of OeMH interventions is lacking. There is a need for practical guidance on the key factors influencing the implementation of interventions that organizations should consider. Stakeholder consultations secure a valuable source of information about these key strategies, barriers, and facilitators that are relevant to successful implementation of OeMH interventions. OBJECTIVE: The objective of this study was to develop a brief checklist to guide the implementation of OeMH interventions. METHODS: Based on the results of a recently published systematic review, we drafted a comprehensive checklist with a wide set of strategies, barriers, and facilitators that were identified as relevant for the implementation of OeMH interventions. We then used a 2-stage stakeholder consultation process to refine the draft checklist to a brief and practical checklist comprising key implementation factors. In the first stage, stakeholders evaluated the relevance and feasibility of items on the draft checklist using a web-based survey. The list of items comprised 12 facilitators presented as statements addressing "elements that positively affect implementation" and 17 barriers presented as statements addressing "concerns toward implementation." If a strategy was deemed relevant, respondents were asked to rate it using a 4-point Likert scale ranging from "very difficult to implement" to "very easy to implement." In the second stage, stakeholders were interviewed to elaborate on the most relevant barriers and facilitators shortlisted from the first stage. The interview mostly focused on the relevance and priority of strategies and factors affecting OeMH intervention implementation. In the interview, the stakeholders' responses to the open survey's questions were further explored. The final checklist included strategies ranked as relevant and feasible and the most relevant facilitators and barriers, which were endorsed during either the survey or the interviews. RESULTS: In total, 26 stakeholders completed the web-based survey (response rate=24.8%) and 4 stakeholders participated in individual interviews. The OeMH intervention implementation checklist comprised 28 items, including 9 (32.1%) strategies, 8 (28.6%) barriers, and 11 (39.3%) facilitators. There was widespread agreement between findings from the survey and interviews, the most outstanding exception being the idea of proposing OeMH interventions as benefits for employees. CONCLUSIONS: Through our 2-stage stakeholder consultation, we developed a brief checklist that provides organizations with a guide for the implementation of OeMH interventions. Future research should empirically validate the effectiveness and usefulness of the checklist.

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 impact of primary headaches on disability outcomes: a literature review and meta-analysis to inform future iterations of the Global Burden of Disease study.

BACKGROUND: The burden and disability associated with headaches are conceptualized and measured differently at patients' and populations' levels. At the patients' level, through patient-reported outcome measures (PROMs); at population level, through disability weights (DW) and years lived with a disability (YLDs) developed by the Global Burden of Disease Study (GBD). DW are 0-1 coefficients that address health loss and have been defined through lay descriptions. With this literature review, we aimed to provide a comprehensive analysis of disability in headache disorders, and to present a coefficient referring to patients' disability which might inform future GBD definitions of DW for headache disorders. METHODS: We searched SCOPUS and PubMed for papers published between 2015 and 2023 addressing disability in headache disorders. The selected manuscript included a reference to headache frequency and at least one PROM. A meta-analytic approach was carried out to address relevant differences for the most commonly used PROMs (by headache type, tertiles of medication intake, tertiles of females' percentage in the sample, and age). We developed a 0-1 coefficient based on the MIDAS, on the HIT-6, and on MIDAS + HIT-6 which was intended to promote future DW iterations by the GBD consortium. RESULTS: A total of 366 studies, 596 sub-samples, and more than 133,000 single patients were available, mostly referred to cases with migraine. Almost all PROMs showed the ability to differentiate disability severity across conditions and tertiles of medication intake. The indexes we developed can be used to inform future iterations of DW, in particular considering their ability to differentiate across age and tertiles of medication intake. CONCLUSIONS: Our review provides reference values for the most commonly used PROMS and a data-driven coefficient whose main added value is its ability to differentiate across tertiles of age and medication intake which underlie on one side the increased burden due to aging (it is likely connected to the increased impact of common comorbidities), and by the other side the increased burden due to medication consumption, which can be considered as a proxy for headache severity. Both elements should be considered when describing disability of headache disorders at population levels.

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.

Clonazepam for the management of sleep disorders.

BACKGROUND: The objectives of this review and meta-analysis of polysomnographic data are those to focus on the clinical use of clonazepam for the management of sleep disorders by re-analyzing clinical trials and randomized clinical trials which have been published in peer-reviewed journals. METHODS: A review of the literature including clinical trials and randomized controlled trials was performed in PubMed®, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement protocol. A random effects model meta-analysis was then carried out for the four more frequently reported polysomnographic measures: total sleep time, sleep latency, sleep efficiency, and periodic leg movement during sleep (PLMS) index. RESULTS: A total of 33 articles were retrieved and screened in full text, of which 18 met the criteria for review; among the latter, nine met the criteria for meta-analysis. The studies included in the review involved patients with insomnia, REM sleep behavior disorder, sleep bruxism, and restless leg syndrome or PLMS which reported, most often, an increase in total sleep time with clonazepam. A clear sleep-promoting effect of clonazepam was found also by meta-analysis. DISCUSSION AND CONCLUSIONS: Our results indicate that the pharmacological treatment of sleep disorders with clonazepam must always be personalized according to the type of patient, the risk of addiction and the concomitant presence of respiratory disorders are key factors to take into account. However, in light of the clinical evidence of the few studies in the literature on the different types of disorders, more studies on the use of clonazepam (also in association with first choice treatments) are definitely needed.

Quantification of retinal ganglion cell loss in patients with homonymous visual field defect due to stroke.

BACKGROUND: To quantify the degree of ganglion cell degeneration through spectral domain optical coherence tomography (SD-OCT) in adult patients with post-stroke homonymous visual field defect. METHODS: Fifty patients with acquired visual field defect due to stroke (mean age = 61 years) and thirty healthy controls (mean age = 58 years) were included. Mean deviation (MD) and pattern standard deviation (PSD), average peripapillary retinal nerve fibre layer thickness (pRNLF-AVG), average ganglion cell complex thickness (GCC-AVG), global loss volume (GLV) and focal loss volume (FLV) were measured. Patients were divided according to the damaged vascular territories (occipital vs. parieto-occipital) and stroke type (ischaemic vs. haemorrhagic). Group analysis was conducted with ANOVA and multiple regressions. RESULTS: pRNFL-AVG was significantly decreased among patients with lesions in parieto-occipital territories compared to controls and to patients with lesions in occipital territories (p = .04), with no differences with respect to stroke type. GCC-AVG, GLV and FLV differed in stroke patients and controls, regardless of stroke type and involved vascular territories. Age and elapsed time from stroke had a significant effect on pRNFL-AVG and GCC-AVG (p < .01), but not on MD and PSD. CONCLUSIONS: Reduction of SD-OCT parameters occurs following both ischaemic and haemorrhagic occipital stroke, but it is larger when the injury extends to parietal territories and increases as time since stroke increases. The size of visual field defect is unrelated to SD-OCT measurements. Macular GCC thinning appeared to be more sensitive than pRNFL in detecting retrograde retinal ganglion cell degeneration and its retinotopic pattern in stroke.

Surgical Complexity and Complications: The Need for a Common Language.

BACKGROUND: Quality measurement and outcome assessment have recently caught an attention of the neurosurgical community, but lack of standardized definitions and methodology significantly complicates these tasks. OBJECTIVE: To identify a uniform definition of neurosurgical complications, to classify them according to etiology, and to evaluate them comprehensively in cases of intracranial tumor removal in order to establish a new, easy, and practical grading system capable of predicting the risk of postoperative clinical worsening of the patient condition. METHODS: A retrospective analysis was conducted on all elective surgeries directed at removal of intracranial tumor in the authors' institution during 2-year study period. All sociodemographic, clinical, and surgical factors were extracted from prospectively compiled comprehensive patient registry. Data on all complications, defined as any deviation from the ideal postoperative course occurring within 30 days of the procedure, were collected with consideration of the required treatment and etiology. A logistic regression model was created for identification of independent factors associated with worsening of the Karnofsky Performance Scale (KPS) score at discharge after surgery in comparison with preoperative period. For each identified statistically significant independent predictor of the postoperative worsening, corresponding score was defined, and grading system, subsequently named Milan Complexity Scale (MCS), was formed. RESULTS: Overall, 746 cases of surgeries for removal of intracranial tumor were analyzed. Postoperative complications of any kind were observed in 311 patients (41.7%). In 223 cases (29.9%), worsening of the KPS score at the time of discharge in comparison with preoperative period was noted. It was independently associated with 5 predictive factors-major brain vessel manipulation, surgery in the posterior fossa, cranial nerve manipulation, surgery in the eloquent area, tumor size >4 cm-which comprised MCS with a range of the total score from 0 to 8 (higher score indicates more complex clinical situations). Patients who demonstrated KPS worsening after surgery had significantly higher total MCS scores in comparison with individuals whose clinical status at discharge was improved or unchanged (3.24 ± 1.55 versus 1.47 ± 1.58; P < 0.001). CONCLUSION: It is reasonable to define neurosurgical complication as any deviation from the ideal postoperative course occurring within 30 days of the procedure. Suggested MCS allows for standardized assessment of surgical complexity before intervention and for estimating the risk of clinical worsening after removal of intracranial tumor. Collection of data on surgical complexity, occurrence of complications, and postoperative outcomes, using standardized prospectively maintained comprehensive patient registries seems very important for quality measurement and should be attained in all neurosurgical centers.

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.

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.

Neurological involvement associated with COVID-19 disease: a study on psychosocial factors.

BACKGROUND: Several people affected by COVID-19 experienced neurological manifestations, altered sleep quality, mood disorders, and disability following hospitalization for a long time. OBJECTIVE: To explore the impact of different neurological symptoms on sleep quality, mood, and disability in a consecutive series of patients previously hospitalized for COVID-19 disease. METHODS: We evaluated 83 patients with COVID-19 around 3 months after hospital discharge. They were divided into 3 groups according to their neurological involvement (i.e., mild, unspecific, or no neurological involvement). Socio-demographic, clinical data, disability level, emotional distress, and sleep quality were collected and compared between the three groups. RESULTS: We found that higher disability, depressive symptoms, and lower sleep quality in patients with mild neurological involvement compared to patients with unspecific and no neurological involvement. Differences between groups were also found for clinical variables related to COVID-19 severity. CONCLUSION: After 3 months from hospital discharge, patients with more severe COVID-19 and mild neurological involvement experienced more psychosocial alterations than patients with unspecific or no neurological involvement. Both COVID-19 and neurological manifestations' severity should be considered in the clinical settings to plain tailored interventions for patients recovering from COVID-19.

Strategies for Implementing Occupational eMental Health Interventions: Scoping Review.

BACKGROUND: The implementation of eMental health interventions, especially in the workplace, is a complex process. Therefore, learning from existing implementation strategies is imperative to ensure improvements in the adoption, development, and scalability of occupational eMental health (OeMH) interventions. However, the implementation strategies used for these interventions are often undocumented or inadequately reported and have not been systematically gathered across implementations in a way that can serve as a much-needed guide for researchers. OBJECTIVE: The objective of this scoping review was to identify implementation strategies relevant to the uptake of OeMH interventions that target employees and detail the associated barriers and facilitation measures. METHODS: A scoping review was conducted. The descriptive synthesis was guided by the RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) framework and the Consolidated Framework for Implementation Research. RESULTS: A total of 31 of 32,916 (0.09%) publications reporting the use of the web-, smartphone-, telephone-, and email-based OeMH interventions were included. In all, 98 implementation strategies, 114 barriers, and 131 facilitators were identified. The synthesis of barriers and facilitators produced 19 facilitation measures that provide initial recommendations for improving the implementation of OeMH interventions. CONCLUSIONS: This scoping review represents one of the first steps in a research agenda aimed at improving the implementation of OeMH interventions by systematically selecting, shaping, evaluating, and reporting implementation strategies. There is a dire need for improved reporting of implementation strategies and combining common implementation frameworks with more technology-centric implementation frameworks to fully capture the complexities of eHealth implementation. Future research should investigate a wider range of common implementation outcomes for OeMH interventions that also focus on a wider set of common mental health problems in the workplace. This scoping review's findings can be critically leveraged by discerning decision-makers to improve the reach, effectiveness, adoption, implementation, and maintenance of OeMH interventions.

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.

Headache onset after vaccination against SARS-CoV-2: a systematic literature review and meta-analysis.

BACKGROUND: Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are used to reduce the risk of developing Coronavirus Disease 2019 (COVID-19). Despite the significant benefits in terms of reduced risk of hospitalization and death, different adverse events may present after vaccination: among them, headache is one of the most common, but nowadays there is no summary presentation of its incidence and no description of its main features. METHODS: We searched PubMed and EMBASE covering the period between January 1st 2020 and August 6th, 2021, looking for record in English and with an abstract and using three main search terms (with specific variations): COVID-19/SARS-CoV-2; Vaccination; headache/adverse events. We selected manuscript including information on subjects developing headache after injection, and such information had to be derived from a structured form (i.e. no free reporting). Pooled estimates and 95% confidence intervals were calculated. Analyses were carried out by vaccine vs. placebo, by first vs. second dose, and by mRNA-based vs. "traditional" vaccines; finally, we addressed the impact of age and gender on post-vaccine headache onset. RESULTS: Out of 9338 records, 84 papers were included in the review, accounting for 1.57 million participants, 94% of whom received BNT162b2 or ChAdOx1. Headache was generally the third most common AE: it was detected in 22% (95% CI 18-27%) of subjects after the first dose of vaccine and in 29% (95% CI 23-35%) after the second, with an extreme heterogeneity. Those receiving placebo reported headache in 10-12% of cases. No differences were detected across different vaccines or by mRNA-based vs. "traditional" ones. None of the studies reported information on headache features. A lower prevalence of headache after the first injection of BNT162b2 among older participants was shown. CONCLUSIONS: Our results show that vaccines are associated to a two-fold risk of developing headache within 7 days from injection, and the lack of difference between vaccine types enable to hypothesize that headache is secondary to systemic immunological reaction than to a vaccine-type specific reaction. Some descriptions report onset within the first 24 h and that in around one-third of the cases, headache has migraine-like features with pulsating quality, phono and photophobia; in 40-60% of the cases aggravation with activity is observed. The majority of patients used some medication to treat headache, the one perceived as the most effective being acetylsalicylic acid.

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.

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.

Long-term neurological manifestations of COVID-19: prevalence and predictive factors.

BACKGROUND: Clinical investigations have argued for long-term neurological manifestations in both hospitalised and non-hospitalised COVID-19 patients. It is unclear whether long-term neurological symptoms and features depend on COVID-19 severity. METHODS: From a sample of 208 consecutive non-neurological patients hospitalised for COVID-19 disease, 165 survivors were re-assessed at 6 months according to a structured standardised clinical protocol. Prevalence and predictors of long-term neurological manifestations were evaluated using multivariate logistic regression analyses. RESULTS: At 6-month follow-up after hospitalisation due to COVID-19 disease, patients displayed a wide array of symptoms; fatigue (34%), memory/attention (31%) and sleep disorders (30%) were the most frequent. At neurological examination, 40% of patients exhibited neurological abnormalities, such as hyposmia (18.0%), cognitive deficits (17.5%), postural tremor (13.8%) and subtle motor/sensory deficits (7.6%). Older age, premorbid comorbidities and severity of COVID-19 were independent predictors of neurological manifestations in logistic regression analyses. CONCLUSIONS: Premorbid vulnerability and severity of SARS-CoV-2 infection impact on prevalence and severity of long-term neurological manifestations.

Outcome prediction in brain tumor surgery: a literature review on the influence of nonmedical factors.

The purpose of the present study was to review the existing data on preoperative nonmedical factors that are predictive of outcome in brain tumor surgery. Our hypothesis was that also the individual characteristics (e.g., emotional state, cognitive status, social relationships) could influence the postoperative course in addition to clinical factors usually investigated in brain tumor surgery. PubMed, Embase, and Scopus were searched from 2008 to 2018 using terms relating to brain tumors, craniotomy, and predictors. All types of outcome were considered: clinical, cognitive, and psychological. Out of 6.288 records identified, 16 articles were selected for analysis and a qualitative synthesis of the prognostic factors was performed. The following nonmedical factors were found to be predictive of surgical outcomes: socio-demographic (age, marital status, type of insurance, gender, socio-economic status, type of hospital), cognitive (preoperative language and cognitive deficits, performance at TMT-B test), and psychological (preoperative depressive symptoms, personality traits, autonomy for daily activities, altered mental status). This review showed that nonmedical predictors of outcome exist in brain tumor surgery. Consequently, individual characteristics (e.g., emotional state, cognitive status, social relationships) can influence the postoperative course in addition to clinical factors.