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Previous evidence suggested that chronic pain is characterized by cognitive deficits, particularly in the social cognition domain. Recently, a new chronic pain classification has been proposed distinguishing chronic primary pain (CPP), in which pain is the primary cause of patients’ disease, and chronic secondary pain (CSP), in which pain is secondary to an underlying illness. The present study aimed at investigating social cognition profiles in the two disorders. We included 38 CPP, 43 CSP patients, and 41 healthy controls (HC). Social cognition was assessed with the Ekman-60 faces test (Ekman-60F) and the Story-Based Empathy Task (SET), whereas global cognitive functioning was measured with the Montreal Cognitive Assessment (MoCA). Pain and mood symptoms, coping strategies, and alexithymia were also evaluated. Correlations among clinical pain-related measures, cognitive performance, and psychopathological features were investigated. Results suggested that CSP patients were impaired compared to CPP and HC in social cognition abilities, while CPP and HC performance was not statistically different. Pain intensity and illness duration did not correlate with cognitive performance or psychopathological measures. These findings confirmed the presence of social cognition deficits in chronic pain patients, suggesting for the first time that such impairment mainly affects CSP patients, but not CPP. We also highlighted the importance of measuring global cognitive functioning when targeting chronic pain disorders. Future research should further investigate the cognitive and psychopathological profile of CPP and CSP patients to clarify whether present findings can be generalized as disorder characteristics.

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.

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.

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.

Background: Transcranial direct current stimulation was suggested to provide beneficial effects in chronic migraine, a condition often associated with medication overuse for which no long-term therapy is available. Methods: We conducted a randomised controlled trial to assess long-term efficacy of transcranial direct current stimulation. Adults diagnosed with chronic migraine and medication overuse were assigned to receive in a 1:1:1 ratio anodal, cathodal, or sham transcranial direct current stimulation daily for five consecutive days, along with standardised drug withdrawal protocol. Primary outcome was 50% reduction of days of headache per month at 12 months. Co-secondary outcomes were 50% reduction of days of headache per month at 6 months, reduction of analgesic intake per month, and change in disability and quality of life, catastrophising, depression, state and trait anxiety, dependence attitude and allodynia intensity. Patients were not allowed to take any migraine prophylaxis drug for the entire study period. Results: We randomly allocated 135 patients to anodal (44), cathodal (45), and sham (46) transcranial direct current stimulation. At 6 and 12 months, the percentage of reduction of days of headache and number of analgesics per month ranged between 48.5% and 64.7%, without differences between transcranial direct current stimulation (cathodal, anodal, or the results obtained from the two arms of treatment, anodal plus cathodal) and sham. Catastrophising attitude significantly reduced at 12 months in all groups. There was no difference for the other secondary outcomes. Conclusions: Transcranial direct current stimulation did not influence the short and long-term course of chronic migraine with medication overuse after acute drug withdrawal. Behavioral and educational measures and support for patients’ pain management could provide long-term improvement and low relapse rate. Trial registration number NCT04228809.

Background: Chronic migraine is a disabling condition that is currently underdiagnosed and undertreated. In this narrative review, we discuss the future of chronic migraine management in relation to recent progress in evidence-based pharmacological treatment. Findings: Patients with chronic migraine require prophylactic therapy to reduce the frequency of migraine attacks, but the only currently available evidence-based prophylactic treatment options for chronic migraine are topiramate and onabotulinumtoxinA. Improved prophylactic therapy is needed to reduce the high burden of chronic migraine in Italy. Monoclonal antibodies that target the calcitonin gene-related peptide (CGRP) pathway of migraine pathogenesis have been specifically developed for the prophylactic treatment of chronic migraine. These anti-CGRP/R monoclonal antibodies have demonstrated good efficacy and excellent tolerability in phase II and III clinical trials, and offer new hope to patients who are currently not taking any prophylactic therapy or not benefitting from their current treatment. Conclusions: Treatment of chronic migraine is a dynamic and rapidly advancing area of research. New developments in this field have the potential to improve the diagnosis and provide more individualised treatments for this condition. Establishing a culture of prevention is essential for reducing the personal, social and economic burden of chronic migraine.

Chronic tension-type headache (CTTH) is a clinical entity where high muscle tension level, in particular in the trapezium area, may induce a pain sensation in the same area. Quantu Molecular Resonance (QMR) has been proved to promote cell regeneration process through direct cell stimulation which is able to decrease local inflammatory reaction an consequently pain level. This study reports a clinical experience of QMR treatment for ten sion-type h eadache, a ssociated to I.A.R.A. (Incontro, Alleanza, Responsabil ità, Autonomia) model®, which increases consciousness of patients who can participate actively to QMR therapy. Treatment has been administrated by specialised nurses.

Background: Even after successful detoxification, 20-40% of subjects presenting chronic migraine with symptomatic medication overuse (CMwMO) relapse into medication overuse within one year. In this restrospective analysis on subjects referred to our center for detoxification, we investigated whether personality traits, dependency-like behaviors and pain coping styles predicted those who relapsed into medication overuse within the 12 months following the detoxification and those who did not.Methods: 63 patients with CMwMO were assessed for personality traits, mood and anxiety, pain coping styles and dependency-like behaviors prior-to and one year after a detoxification program.Results: Of the 42 subjects who attended 1-year follow-up interviews, 11 relapsed into medication overuse despite a temporary benefit from detoxification and did not show clinical or psychological improvement, instead reporting increased anxiety and unmodified perpetuation of severe dependency-like behaviors. In contrast, subjects who did not relapse into medication overuse had clinical improvements that generalized to untreated domains, including decreased depressive symptoms and dependency-like behaviors, although showing unmodified low internal control over pain.Conclusions: Subjects who did not fall into medication overuse throughout the 12 months following the detoxification showed improved clinical, affective and dependence-related outcomes, but not pain coping strategies. Conversely, subjects who relapsed within one year into CMwMO continued to experience significant disability, pain intensity, and dependency-like behaviors. We believe that the persistence of maladaptive pain coping strategies and residual symptomatology increase the risk for recurrent relapses, against which pharmacological interventions are only partially effective. Further studies investigating predictors of relapse are needed to inform multi-disciplinary interventions for CMwMO.

Psychiatric disorders in migraine patients have a higher prevalence than general population. The presence of psychiatric comorbidities may influence the complexity of the migraine pictures and be related to medication overuse. Severely impaired chronic migraineurs presenting with medication overuse are a challenge for headache clinics. Psychiatric comorbities, such as dependency-like behaviors, anxiety and mood symptoms, might account for headache-related disability and recurrent relapses into medication overuse after a successful detoxification. Within a sample of 63 chronic migraineurs with medication overuse and severe disability, we investigated to which extent clinical severity, affective states and attitudes about medication impact the overall functioning at time of detoxification. To unravel whether some of these factors could predict their long-term outcome, we followed and retest them 1 year after with drawal. We hypothesized that the detoxification would have led to a partial improvement and not modified the attitudes toward medication and dependence. Detoxification improves most of the clinical and affective measures, but does not free from significant levels of pain intensity and headache-related disability. The partial benefit from detoxification, the severity bias and the maladaptive cognitive profile led us to believe that subgroups of chronic-relapsing migraineurs deserve a multidisciplinary approach that addresses not only the reduction of clinical severity but also specific cognitive and behavioral impairments.

Patients with chronic migraine developing medication-overuse headache (MOH) show dependency-like behaviors such as loss of control over analgesics despite adverse consequences on headaches, high rates of relapse after withdrawal from symptomatic medications, and compromised social functioning. Neuroimaging research suggests a common pathophysiology between substance-use disorders and MOH, which involves functional alterations in fronto-striatal networks, particularly in the orbitofrontal region of prefrontal cortex. These findings could explain the impaired decision-making observed in substance-use disorders. We hypothesize that MOH could share fronto-striatal circuit dysfunction and relative decision- making deficit with addiction. We further examine whether this deficit is a persistent cognitive trait or a reversible consequence of medication overuse. This study shows a dataset of 50 patients with MOH before the detoxification. All patients underwent a complete neurological and psychiatric examination. Psychiatric examination consisted of a clinical interview, Structured Clinical Interview for DSM-IV TR Axis II Personality Disorders, Anxiety and Depression Hamilton Scales, Severity of Dependence Scale. The neurological examination included the migraine disability assessment questionnaire. Neuropsychological assessment of fronto-striatal circuits was investigated using the Iowa gambling task (IGT). Twenty patients monitored for any relapse into medication overuse had 12 months of follow-up. Our sample, characterized by high rates of disability and dependency-like behaviors, exhibited a deficit in IGT performance, indicating an overall impairment in decision-making. All the 20 patients showed neurological and psychiatric improvement at 12-month follow-up, notwithstanding the overuse relapse, but a persistent IGT deficit was found. To our knowledge this is the first study that assesses this cognitive function in patients with MOH. Medication-overuse headache seems to

Objective Orbitofrontal cortex (OFC) dysfunction and poor decision making have been described in patients with chronic migraine and medication overuse. These neurobiological underpinnings might explain dependency-like behaviors often described in this condition, such as loss of control over painkillers, high rates of relapse after detoxification, and compromised social functioning. We investigate whether the OFC impairment was a persistent trait in migraine, independent of clinical and affective features, a dynamic result of the need to cope with the increased pain and disability, or a temporary consequence of medication overuse. Methods For this purpose, we compared 40 chronic migraineurs with medication overuse, 40 episodic migraineurs, and 40 matched healthy controls. The examination consisted of a clinical interview, Anxiety and Depression Hamilton Scales, Severity of Dependence Scale, and Migraine Disability Assessment questionnaire. A neuropsychological assessment of orbitofrontal function was made through the Iowa Gambling Task (IGT). Chronic migraineurs with medication overuse were followed for a year after detoxification. Results We found an impaired decision-making performance among chronic and episodic migraineurs that seems independent of the patients' clinical and affective status. Contrary to the psychiatric and clinical improvement shown 1 year after the detox, CM patients exhibited a persistent IGT deficit. No significant differences in OFC functioning were found between the CM patients who relapsed into medication overuse after detox and those who did not. Conclusions The present findings suggest the presence of a persistent OFC dysfunction in migraine as a psychobiologic trait that is not influenced by the presence of medication overuse, the clinical severity of the disease, or the patient's affective status. Further studies are needed to elucidate the etiopathological role of OFC in migraine and medication overuse.