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.

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.

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.

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.

Older Adults' Risk Perception during the COVID-19 Pandemic in Lombardy Region of Italy: A Cross-sectional Survey.

During COVID-19 pandemic, older adults are the segment of the population at higher health risk. Given the important role the risk perception has in influencing both the behaviors and psychological well-being, it appears useful exploring this factor in this segment of the population. Despite different studies already described the factors influencing the risk perception, few focused on older adults. For this reason, we investigated risk perception in 514 people over 60 years during the lockdown. We administered a structured interview collecting socio-demographic information, sources of information used, actions undertaken to avoid contagion, and risk perception. Risk perception related to COVID-19 was significantly lower than the perceived risk associated with other threats, and it was correlated to the number of sources of information used but not to the actions undertaken. Furthermore, we found higher risk perception in who knew infected persons, and a negative correlation between the risk perception and age, with the over 75 perceiving a lower risk of getting infected compared to the younger participants. Our results should be taken as informative for future studies. Indeed, further studies on the older adults and the risk perception during emergencies are needed to better orient both communication and supporting strategies.

Employment in Myasthenia Gravis: A Systematic Literature Review and Meta-Analysis.

INTRODUCTION: Myasthenia gravis (MG) is an autoimmune disease whose period of typical onset is around 20-40 years (i.e., early onset), thus in the peak of working age, or around 60-80 years (i.e., late onset). However, the information on work-related issues and employment status are sparse and not systematically reported. Therefore, we performed a systematic literature review with meta-analysis to address the employment status of MG patients. METHODS: We searched for papers reporting employment status on participants with MG published between January 2000 and May 2019. Information on employment was extracted. Random-effects models were used to produce meta-analytic estimates for the proportion of employed patients. RESULTS: In total, 1,045 records were retrieved, of which 19 fitted the inclusion criteria. In total, 3,600 participants (average age 47.5, range 35-60) were included in the studies and 1,579 of them were employed. The proportion of employed patients varied from 28 to 82%, with an extreme heterogeneity between studies. Overall, the pooled proportion of workers was 50% (95% CI 41-60%). Subgroup analyses suggested a possible, although not significant, higher proportion of workers among women, younger participants, those with a higher level of education, shorter MG duration, and less frequently thymectomized, whereas a lower proportion was observed among those with generalized, bulbar, and respiratory symptoms. CONCLUSIONS: The results of our meta-analysis show that the percentage of employment is considerably low if we take into account that the mean age of MG patients involved in the included studies was around 48 years, thus in peak of working life. Therefore, it is important to understand what kind of influence MG exerts on work dynamics.

A Qualitative Study On Patients With Chronic Migraine With Medication Overuse Headache: Comparing Frequent And Non-Frequent Relapsers.

BACKGROUND: It is common clinical experience that, after structured withdrawal, some patients with chronic migraine and medication overuse headache (CM with MOH) are more prone than others to relapse and to be in need of further structured treatments. Our aim was to explore similarities and differences between frequent relapsers (FRs) and non-frequent relapsers (NFRs) by considering their point of view, perceptions, and perspective of their subjective experience with relapse into CM with MOH. METHODS: Patients were consecutively recruited on occasion of a structured withdrawal treatment and were interviewed individually about their headache experience and their perspectives on relapse into CM with MOH. We considered FR those patients requiring 2 or more structured withdrawals for MOH within 3 years. A narrative approach with no preconceived coding schemes was employed. To facilitate coding, categorization and organization of data the software QRS NVivo 11.0 was used: themes were defined as common to FR and NFR, or peculiar (by frequency or content) to one of the 2 groups. RESULTS: Sixteen patients (13 women; mean age of 53) were interviewed: 7 were classified as FRs. A total of 22 themes emerged from 552 single quotations (the 10 most relevant covered 82% of the entire body of quotations). Four themes were commonly reported by both FR and NFR patients, and 6 were peculiar to one group only. Common aspects included issues connected to the dilemma between disclosing, concealing and the feelings of isolation around MOH, the idea of being addicted to medication, presence of anxiety, and the attempt to use non-pharmacological therapies as an alternative to medication. Peculiar aspects included causal attribution (FRs attributed headache to uncontrollable factors); future expectations at the time point of withdrawal (FRs were generally resigned); high-performance functioning (FRs believed they are "forced" to reach high levels of performance as a consequence of others' inability); coping strategies (FRs tended to "passively accept" problems and showed avoidance-related behaviors). Moreover, FRs were less frequently aware of their problems and described more frequently depressive symptoms. CONCLUSIONS: Our results highlight that some differences between FR and NFR patients with CM and MOH exist. Frequent relapsers among patients with CM and MOH reported some important peculiarities of the lived experience of having chronic migraine; clinicians should recognize these psychosocial aspects such as social relationships, future expectations, the experience of illness, medication management, and how the withdrawal experience is regarded, as they may be associated with frequent relapse into MOH.

Validation of a self-reported instrument to assess work-related difficulties in patients with migraine: the HEADWORK questionnaire.

BACKGROUND: The degree to which work-related difficulties are recognized in headache research is poor and often carried out with inadequate information such as "reduced ability to work as usual", which do not capture at all the variety of difficulties and the factors that impact over them. The aim of this paper is to present the validation of the HEADWORK questionnaire, which addresses the amount and severity of difficulties in work-related tasks and the factors that impact over them. METHODS: We developed a set of items based on a previous literature review and patients' focus groups and tested it on a wide set of patients with episodic and chronic migraine attending eight different Italian headache centers. HEADWORK factor structure was assessed with exploratory and confirmatory factor analysis; internal consistency and construct validity were addressed as well. RESULTS: The validation sample (N = 373) was mostly composed of patients with episodic migraine without aura (64.3%) and of females (81%). Factor analysis retrieved two different scales: "Work-related difficulties", composed of eleven items which explain 67.1% of the total variance, and "Factors contributing to work difficulties", composed of six items which explain 52.1% of the total variance. Both HEADWORK subscales have good measurement properties, with higher scores being associated to higher disability, lower quality of life, lower productivity, higher headache frequency and pain intensity. CONCLUSIONS: HEADWORK is a 17-item, two-scale questionnaire addressing the impact of migraine on work-related difficulties in terms of difficulties in general or specific skills, and the factors contributing to these difficulties, defined as negative impact on work tasks. It can be used to address disability weights for the purpose of calculating the burden of migraine, and to assess the balance between therapeutic and side effects of medication on productivity.

Quality of life, functioning and participation of children and adolescents with visual impairment: A scoping review.

BACKGROUND: Vision has a key role in children's neuromotor, cognitive and social development. Children with visual impairment attain developmental milestones at later stages and are at higher risk of developing psychological disorders and social withdrawn. AIMS: We performed a scoping review to summarize the mostly used instruments assessing the impact of visual impairment on quality of life, functioning and participation of children and adolescents. In addition, the main findings of the included studies are discussed. METHODS AND PROCEDURES: We searched for papers assessing quality of life, functioning and participation of children and adolescents with visual impairment from 0 to 18 years old conducted between 2000 and 2023. OUTCOMES AND RESULTS: In total, 69 studies met the inclusion criteria and were included in the review. Child self-report, caregivers-proxy and self-report questionnaires as well as interviews were used. The results showed that quality of life, functioning and participation are significantly reduced in children and adolescents with visual impairment, and that the impact depends on different factors (e.g., severity of the impairment, age). CONCLUSIONS AND IMPLICATIONS: Considering the significant impact of visual impairment on quality of life, functioning and participation on this population, it is fundamental to develop integrated and multi-dimensional assessment programs that evaluate the impact of visual impairment on those dimensions considering different contexts of life (e.g., family, school, leisure time). WHAT THIS PAPER ADDS?: The present review aims to give an overview of what is known about the impact of visual impairment on quality of life, functioning and participation of children and adolescents. We assumed a biopsychosocial perspective which, in line with the definition of health by the International Classification of Functioning, Disability and Health (WHO, 2001), considered how body functions and structures, functioning, participation and environmental factors dynamically interact to define the health, or the disease, status of a person at a certain moment of life. We reported the most used instruments for the assessment of quality of life, participation, and functioning, with a specific interest on Patient-Reported Outcome Measures and self-report measures. By reporting the different instruments used, we gave a broad overview about the available tools that can be used in clinical as well as in research field to assess quality of life, functioning and participation in this population. Additionally, the review of the existing literature allowed us to demonstrate that those dimensions are negatively impacted by visual impairment and thus they should be considered in the assessment programs. Specifically, there is the need to provide more integrated assessment programs that investigate the impact of visual impairment on children and adolescents' social and emotional wellbeing, everyday functioning and social relationship, considering their subjective experience together with the one of caregivers, teachers, health care professionals, and other relevant adults involved in their life. Additionally, it is essential to plan and implement multidimensional assessment programs that consider how all areas of life are differently impacted by visual impairment.

Societal and personal impact of migraine.

Migraine is one of the main causes of years lived with disability (YLDs) worldwide, as showed in the Global Burden of Diseases Study. Its influence on patients' life is relevant and pervasive, with a specific impact on social, family, and work functioning, considering that migraine mainly affects adults under the age of 50. Several studies demonstrated that relations inside the family as well as in every social context are negatively influenced by migraine. According to the results of studies and surveys from different countries, patients' daily activities are often limited during migraine attacks, particularly in terms of performance in social and domestic activities and in terms of reduced productivity in work and school duties. Also an interictal burden is present. Migraineurs are conditioned by the fear of the next attack, often suffer from comorbid conditions such as anxiety and depression, and are subject to different forms of stigma. Consequently, migraine implies relevant costs for the individuals and for society, with higher figures for indirect costs (related to reduced participation and to limited productivity) than indirect costs (related to drugs, medical visits, examinations, and hospitalization).

A Single-Group Study on the Effect of OnabotulinumtoxinA in Patients with Chronic Migraine Associated with Medication Overuse Headache: Pain Catastrophizing Plays a Role.

Pain catastrophizing and cutaneous allodynia are commonly altered in patients with chronic migraine associated with medication overuse headache (CM-MOH) and tend to improve in parallel with clinical improvement. The relation between pain catastrophizing and cutaneous allodynia is poorly understood in patients with CM-MOH receiving OnabotulinumtoxinA therapy. In this single-arm open-label longitudinal observational study, patients with CM-MOH were assigned to structured withdrawal and then administered OnabotulinumtoxinA (5 sessions on a three-month basis, 195 UI per 31 sites). Headache frequency, medication intake, disability, impact, cutaneous allodynia and pain catastrophizing were evaluated with specific questionnaires. In total, 96 patients were enrolled and 79 completed the 12-month follow-up. With the exclusion of cutaneous allodynia and the magnification subscale of the pain catastrophizing questionnaire, all variables showed significant improvement by the sixth month, which was maintained at 12 months. Reduction of pain catastrophizing, and particularly of its helplessness subscale, was a significant predictor of reduction in headache frequency and medication intake. Pain catastrophizing is often implicated in the clinical improvement in patients with CM-MOH receiving behavioral treatments, but, in this study, also showed a role in patients receiving OnabotulinumtoxinA; combining OnabotulinumtoxinA and behavioral treatments specifically addressing pain catastrophizing might further enhance patients' clinical outcome.

Psychosocial factors as main predictors of quality of life 5 years after stroke: a cross-sectional study from a third-level Italian center.

Stroke causes a significant reduction in health-related quality of life (HRQoL), and studies addressing its predictors often rely on models with few variables. This study aimed to assess the degree to which health status, health habits, and features of the environment predict HRQoL in stroke survivors with stable clinical condition. WHO Quality of Life questionnaire for old-Age subjects (WHOQOL-AGE) was used to assess HRQoL. We ran a multivariable linear regression to predict WHOQOL-AGE variation, entering measures of health state, bad habits, healthy behaviors, physical environment features, and social support. Patients were stroke survivors with a stable clinical condition, distance from acute event of more than 6 months, and National Institutes of Health Stroke Scale (NIHSS) of 10 or less. A total of 122 participants (47 females, 97 with ischemic stroke) were enrolled, the mean age was 64.1, mean NIHSS 2.9, and mean distance from the acute event was 5.1 years. State anxiety (ß = -0.202), trait anxiety (ß = -0.232), depression (ß = -0.255), social support (ß = 0.247), and functional independence (ß = -0.210) predicted WHOQOL-AGE variation (Adj. R2 = 0.549). Our results show that psychological symptoms, reduced social network, and functional dependence together have a negative impact on HRQoL. These elements, which are partly stroke-specific, should be taken into account in the recovery process to enhance patients' health outcomes.

An observational, cross-sectional and monocentric study assessing psychological and cognitive features as main predictors of psychological well-being in stroke survivors.

Well-being is a relevant outcome after stroke, potentially impacted by mental health difficulties. We addressed the psychological and cognitive predictors of psychological well-being in a sample of 122 stroke survivors (75 males, 97 with ischemic stroke; mean age 64.1, mean NIHSS 2.9, mean distance from the acute event 5.1 years) admitted to the 'Carlo Besta' Neurological Institute. Trait anxiety (ß = -0.257), state anxiety (ß = -0.208) and symptoms of depression (ß = -0.484) significantly predicted well-being variation (Adj. R2 = 0.687). These potentially modifiable factors are promising targets for interventions to reduce the burden of illness and enhance the recovery process.

A Preliminary Analysis on the Feasibility and Short-Term Efficacy of a Phase-III RCT on Mindfulness Added to Treatment as Usual for Patients with Chronic Migraine and Medication Overuse Headache.

This preliminary analysis of a single-blind phase-III RCT aims to compare the feasibility and short-term efficacy of mindfulness as an add-on to treatment as usual (TaU) in the management of patients with chronic migraine (CM) and medication overuse headache (MOH). Patients were randomized to either TaU (structured withdrawal of overused drugs, patient education and pharmacological prophylaxis) or TaU + MIND, wherein patients additionally received six 90 min weekly group sessions of mindfulness-based therapy. Repeated measures analyses were used to test whether patients in the two arms showed different course with regard to headache frequency and medication intake over a three-month period. Drop-out rates were not different between the two groups: 6/89 (6.7%) and 9/88 (10.2%) among those in TaU and TaU + MIND, respectively. A significant effect of time for all variables was shown, together with a significant effect of time by group, favoring TaU + MIND condition for headache frequency (p = 0.025) and NSAID intake (p = 0.007), controlling for age and CM duration. In total, 45/83 (54.2%) and 69/79 (75.9%) of the patients allocated to TaU and TaU + MIND, respectively, achieved 50% or more headache-day reduction (chi-squared 8.38, p = 0.004). Our preliminary analysis indicates that adding six mindfulness-based sessions to TaU was feasible and showed short-term efficacy in the treatment of patients with CM and MOH.

Social Network and Environment as Determinants of Disability and Quality of Life in Aging: Results From an Italian Study.

Background: The increase in life expectancy is leading to a worldwide increase in chronic diseases and disability, with significant concern about their management and long-term care. Investigating the aging process using a bio-psychosocial perspective is essential to understanding how to reduce disability and improve the quality of life of aging people. This study aims to explore the role of social networks and built environment as predictors of disability and quality of life in the Italian population aged over 50 years. Materials and Methods: The research protocol is composed of several tools: World Health Organization Disability Assessment Scale 2.0 (WHODAS 2.0), World Health Organization Quality of Life Assessment in Aging (WHOQOL-AGE), Social Network Index (SNI), the Courage Built Environment Self-Reported Questionnaire (CBE-SR), and collection of sociodemographic information and information on health system coverage. Results: A total of 431 people were administered the protocol, and among them, 209 were males and 222 were females, with a mean age of 70 years. The majority of the sample reported earning a middle or high school diploma, and 60.6% of the sample declared to have a good health status. The results showed that people with a good social support network have higher levels of functioning and quality of life. However, the built environment did not significantly predict either disability or quality of life. Conclusions: These results could provide elements for dialogue with institutions and policymakers. This is fundamental to develop active policies aimed at the implementation of services and systems to promote healthy aging process.

Neurological and Mental Health Symptoms Associated with Post-COVID-19 Disability in a Sample of Patients Discharged from a COVID-19 Ward: A Secondary Analysis.

Recent studies suggest that COVID-19 survivors may experience long-term health consequences: in particular, neurological and mental health symptoms might be associated with long-term negative outcomes. This study is a secondary analysis of a larger cohort study and aims to determine the extent to which neurological and mental health sequelae are associated with survivors' disability. Participants include COVID-19 survivors, with no pre-morbid brain conditions, who were discharged from the COVID-19 Unit of the ASST Spedali Civili Hospital between February and April 2020. At an average of 3.5 months after discharge, they were submitted to a neurological examination and completed the WHO Disability Assessment Schedule (WHODAS-12), the Hospital Anxiety and Depression Score, the Pittsburgh Sleep Quality Index and the Montreal Cognitive Assessment. Multivariable regression analysis was carried out to analyze variables that explain WHODAS-12 variation. In total, 83 patients (63 males, average age 66.9, 95% CI: 64.2-69.7) were enrolled; average WHODAS-12 was 13.2 (95% CI: 9.7-16.6). Cognitive dysfunction, anxiety, fatigue, and hyposmia/hypogeusia explained 28.8% of WHODAS-12 variation. These findings underline the importance and need for longitudinal follow-up assessments after recovery from COVID-19 and suggest the need for early rehabilitation of residual symptoms to enhance patients' functioning.

Effect of a Mindfulness-Based Intervention for Chronic Migraine and High Frequency Episodic Migraine in Adolescents: A Pilot Single-Arm Open-Label Study.

In this single-arm pilot open-label study we examined the effect of a mindfulness-based intervention on reduction of headache frequency after 12 months in adolescents aged 12-18 with chronic or high-frequency migraine without aura. Adolescents were recruited at the headache center of the C. Besta Neurological Institute and followed-up for 12 months. The mindfulness-based intervention was delivered in small groups and consisted of six weekly group sessions of guided meditation, and one booster session 15 days after. Patients filled in questionnaires assessing headache frequency (primary endpoint), medication intake, disability, anxiety, depression, catastrophizing, and caregivers' burden. Within-person ANOVA was used to address variation of endpoints over time. Thirty-five out of 37 patients completed the study for primary endpoints, and 33 for secondary endpoints. Headache frequency dropped from 21.3 (95% CI 18.5; 24.1) to 9.6 (95% CI 6.1; 13.1) days per month at 12 months (F = 30.5, p < 0.001); 23 patients out of 35 (65.7%) achieved a headache frequency reduction greater than or equal to 50%. Significant improvements were also reported for medication intake (F = 18.7, p < 0.001), disability (F = 3.8, p = 0.027), trait anxiety (F = 5.1, p = 0.009), symptoms of depression (F = 9.5, p < 0.001), and catastrophizing (F = 23.6, p < 0.001). In conclusions, our study shows a reduction of headache attacks in adolescents who follow a mindfulness-based program, suggesting benefit of this nonpharmacological approach.

Non-Pharmacological Approaches to Headaches: Non-Invasive Neuromodulation, Nutraceuticals, and Behavioral Approaches.

Significant side effects or drug interactions can make pharmacological management of headache disorders very difficult. Non-conventional and non-pharmacological treatments are becoming increasingly used to overcome these issues. In particular, non-invasive neuromodulation, nutraceuticals, and behavioral approaches are well tolerated and indicated for specific patient categories such as adolescents and pregnant women. This paper aims to present the main approaches reported in the literature in the management of headache disorders. We therefore reviewed the available literature published between 2010 and 2020 and performed a narrative presentation for each of the three categories (non-invasive neuromodulation, nutraceuticals, and behavioral therapies). Regarding non-invasive neuromodulation, we selected transcranial magnetic stimulation, supraorbital nerve stimulation, transcranial direct current stimulation, non-invasive vagal nerve stimulation, and caloric vestibular stimulation. For nutraceuticals, we selected Feverfew, Butterbur, Riboflavin, Magnesium, and Coenzyme Q10. Finally, for behavioral approaches, we selected biofeedback, cognitive behavioral therapy, relaxation techniques, mindfulness-based therapy, and acceptance and commitment therapy. These approaches are increasingly seen as a valid treatment option in headache management, especially for patients with medication overuse or contraindications to drug treatment. However, further investigations are needed to consider the effectiveness of these approaches also with respect to the long-term effects.