Redefining migraine prevention: early treatment with anti-CGRP monoclonal antibodies enhances response in the real world.

BACKGROUND: Anti-CGRP monoclonal antibodies (anti-CGRP MAbs) are approved and available treatments for migraine prevention. Patients do not respond alike and many countries have reimbursement policies, which hinder treatments to those who might respond. This study aimed to investigate clinical factors associated with good and excellent response to anti-CGRP MAbs at 6 months. METHODS: European multicentre, prospective, real-world study, including high-frequency episodic or chronic migraine (CM) patients treated since March 2018 with anti-CGRP MAbs. We defined good and excellent responses as ≥50% and ≥75% reduction in monthly headache days (MHD) at 6 months, respectively. Generalised mixed-effect regression models (GLMMs) were used to identify variables independently associated with treatment response. RESULTS: Of the 5818 included patients, 82.3% were females and the median age was 48.0 (40.0-55.0) years. At baseline, the median of MHD was 20.0 (14.0-28.0) days/months and 72.2% had a diagnosis of CM. At 6 months (n=4963), 56.5% (2804/4963) were good responders and 26.7% (1324/4963) were excellent responders. In the GLMM model, older age (1.08 (95% CI 1.02 to 1.15), p=0.016), the presence of unilateral pain (1.39 (95% CI 1.21 to 1.60), p<0.001), the absence of depression (0.840 (95% CI 0.731 to 0.966), p=0.014), less monthly migraine days (0.923 (95% CI 0.862 to 0.989), p=0.023) and lower Migraine Disability Assessment at baseline (0.874 (95% CI 0.819 to 0.932), p<0.001) were predictors of good response (AUC of 0.648 (95% CI 0.616 to 0.680)). These variables were also significant predictors of excellent response (AUC of 0.691 (95% CI 0.651 to 0.731)). Sex was not significant in the GLMM models. CONCLUSIONS: This is the largest real-world study of migraine patients treated with anti-CGRP MAbs. It provides evidence that higher migraine frequency and greater disability at baseline reduce the likelihood of responding to anti-CGRP MAbs, informing physicians and policy-makers on the need for an earlier treatment in order to offer the best chance of treatment success.

High-frequency episodic migraine: Time for its recognition as a migraine subtype?

BACKGROUND: High-frequency episodic migraine (HFEM) has gained attention in the field of headache research and clinical practice. In this narrative review, we analyzed the available literature to assess the evidence that could help decide whether HFEM may represent a distinct clinical and/or biological entity within the migraine spectrum. METHODS: The output of the literature search included 61 papers that were allocated to one of the following topics: (i) socio-demographic features and burden; (ii) clinical and therapeutic aspects; (iii) pathophysiology; and (iv) classification. RESULTS: Multiple features differentiate subjects with HFEM from low-frequency episodic migraine and from chronic migraine: education, employment rates, quality of life, disability and psychiatric comorbidities load. Some evidence also suggests that HFEM bears a specific profile of activation of cortical and spinal pain-related pathways, possibly related to maladaptive plasticity. CONCLUSIONS: Subjects with HFEM bear a distinctive clinical and socio-demographic profile within the episodic migraine group, with a higher disease burden and an increased risk of transitioning to chronic migraine. Recognizing HFEM as a distinct entity is an opportunity for the better understanding of migraine and the spectrum of frequency with which it can manifest, as well as for stimulating further research and more adequate public health approaches.

Association of anti-calcitonin gene-related peptide with other monoclonal antibodies for different diseases: A multicenter, prospective, cohort study.

BACKGROUND AND PURPOSE: Although there is extensive evidence about the safety of monoclonal antibodies against calcitonin gene-related peptide (anti-CGRP mAbs) in combination with traditional drugs, scarce data are available on the safety of their combination with other mAbs. This study aimed to evaluate the 6-month effectiveness and tolerability of anti-CGRP mAbs in combination with other mAbs for different diseases. METHODS: Patients included in the Italian Headache Registry and treated concomitantly with an anti-CGRP mAb and another mAb were included. Effectiveness outcomes for migraine included reduction from baseline of monthly headache days (MHDs), Migraine Disability Assessment (MIDAS) score, Headache Impact Test-6 (HIT-6) scores, and Patients' Global Impression of Change (PGIC) scale. Adverse events (AEs) were recorded. RESULTS: Thirty-eight patients were included. In 27 patients (71.1%), the anti-CGRP mAb was added to a previously ongoing mAb. Nine patients (23.7%) discontinued one of the two mAbs before the end of treatment (seven discontinued the anti-CGRP mAb and two the other mAb). One patient discontinued for AEs. Anti-CGRP mAbs were discontinued due to ineffectiveness (n = 5, 55.5%) and one each (11.1%) for clinical remission and lost to follow-up. MHDs significantly decreased from baseline to 3 months (p < 0.0001) and 6 months (p < 0.001), as did the MIDAS and the HIT-6 scores at 3 and 6 months (p < 0.001). For anti-CGRP mAbs, 27.4% of patients reported PGIC ≥ 5 at 3 months and 48.3% at 6 months. Mild AEs associated with introduction of a second mAb were detected in six patients (15.8%). CONCLUSIONS: In this real-world study, anti-CGRP mAbs showed safety and effectiveness when administered concomitantly with other mAbs.

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

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

Differences in Trunk Acceleration-Derived Gait Indexes in Stroke Subjects with and without Stroke-Induced Immunosuppression.

Background: Stroke-induced immunosuppression (SII) represents a negative rehabilitative prognostic factor associated with poor motor performance at discharge from a neurorehabilitation unit (NRB). This study aims to evaluate the association between SII and gait impairment at NRB admission. Methods: Forty-six stroke patients (65.4 ± 15.8 years, 28 males) and 42 healthy subjects (HS), matched for age, sex, and gait speed, underwent gait analysis using an inertial measurement unit at the lumbar level. Stroke patients were divided into two groups: (i) the SII group was defined using a neutrophil-to-lymphocyte ratio ≥ 5, and (ii) the immunocompetent (IC) group. Harmonic ratio (HR) and short-term largest Lyapunov's exponent (sLLE) were calculated as measures of gait symmetry and stability, respectively. Results: Out of 46 patients, 14 (30.4%) had SII. HR was higher in HS when compared to SII and IC groups (p < 0.01). HR values were lower in SII when compared to IC subjects (p < 0.01). sLLE was lower in HS when compared to SII and IC groups in the vertical and medio-lateral planes (p ≤ 0.01 for all comparisons). sLLE in the medio-lateral plane was higher in SII when compared to IC subjects (p = 0.04). Conclusions: SII individuals are characterized by a pronounced asymmetric gait and a more impaired dynamic gait stability. Our findings underline the importance of devising tailored rehabilitation programs in patients with SII. Further studies are needed to assess the long-term outcomes and the role of other clinical features on gait pattern.

Peripheral Endocannabinoid Components and Lipid Plasma Levels in Patients with Resistant Migraine and Co-Morbid Personality and Psychological Disorders: A Cross-Sectional Study.

Resistant migraine characterizes those patients who have failed at least three classes of migraine prophylaxis. These difficult-to-treat patients are likely to be characterized by a high prevalence of psychological disturbances. A dysfunction of the endocannabinoid system (ECS), including alteration in the levels of endocannabinoid congeners, may underlie several psychiatric disorders and the pathogenesis of migraines. Here we explored whether the peripheral gene expression of major components of the ECS and the plasma levels of endocannabinoids and related lipids are associated with psychological disorders in resistant migraine. Fifty-one patients (age = 46.0 ± 11.7) with resistant migraine received a comprehensive psychological evaluation according to the DSM-5 criteria. Among the patients, 61% had personality disorders (PD) and 61% had mood disorders (MD). Several associations were found between these psychological disorders and peripheral ECS alterations. Lower plasma levels of palmitoiletanolamide (PEA) were found in the PD group compared with the non-PD group. The MD group was characterized by lower mRNA levels of diacylglycerol lipase α (DAGLα) and CB2 (cannabinoid-2) receptor. The results suggest the existence of peripheral dysfunction in some components of the ECS and an alteration in plasma levels of PEA in patients with resistant migraine and mood or personality disorders.

Arterial hypertension in the chronic evolution of migraine: bystander or risk factor? An overview.

BACKGROUND: Several risk factors are associated with the chronic evolution of migraine. Clinical and preclinical studies have provided data about the role of hypertension (HT) as one of the potential modifiable risk factors of chronic migraine (CM). This review is focused on the biological and clinical evidence supporting common mechanisms underlying HT and migraine and the potential role of HT in the transition from episodic to chronic migraine. METHODS: We conducted a narrative review from a literature search covering the available evidence from studies investigating: i) the role of HT in the transition to CM in clinical practice; ii) the biological mechanisms potentially underpinning the association between HT and evolution to CM; iii) the role of antihypertensive medications in migraine prophylaxis. RESULTS: HT proved to be at the base of multiple mechanisms underlying migraine and migraine chronicization. Endothelial dysfunction, blood-brain barrier alterations, calcitonin gene-related peptide signaling, and renin-angiotensin-aldosterone system dysregulation are involved in the worsening effect of HT on migraine frequency, and the role of HT in the transition to CM is supported by clinical observations. CONCLUSIONS: The observed evidence supports HT contribution to CM evolution due to shared pathophysiologic mechanisms. While a bidirectional influence appears to be ascertained, data are still lacking about the one-way role of HT as direct risk factor for CM transition. Further research is needed to confirm a causal role of HT in this process.

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.

Expression of miR-155 in monocytes of people with migraine: association with phenotype, disease severity and inflammatory profile.

BACKGROUND: miR-155 is involved in the generation and maintenance of inflammation and pain, endothelial function and immune system homeostasis, all functions that are relevant for migraine. The present study aims to assess the levels of miR-155 in migraine subtypes (episodic and chronic) in comparison to age- and sex-matched healthy controls. METHODS: This is a cross-sectional, controlled, study involving three study groups: I) episodic migraine (n = 52, EM), II) chronic migraine with medication overuse (n = 44, CM-MO), and III) healthy controls (n = 32, HCs). We assessed the interictal gene expression levels of miR-155, IL-1ß, TNF-α, and IL-10 in peripheral blood monocytes using rtPCR. The monocytic differentiation toward the M1 (pro-inflammatory) or M2 (anti-inflammatory) phenotypes was assessed in circulating monocytes with flow cytometry analysis and cell sorting. RESULTS: miR-155 gene expression was higher in CM-MO group (2.68 ± 2.47 Relative Quantification - RQ) when compared to EM group (1.46 ± 0.85 RQ, p = 0.006) and HCs (0.44 ± 0.18 RQ, p = 0.001). In addition, miR-155 gene expression was higher in EM group when compared to HCs (p = 0.001). A multivariate analysis confirmed the difference between EM and CM-MO groups after correction for age, sex, smoking habit, preventive treatment, aura, presence of psychiatric or other pain conditions. We found higher gene expression of IL-1ß, TNF-α, and lower gene expression of IL-10 in migraine participants when compared to HCs (p = 0.001 for all comparisons). TNF-α and IL-10 genes alterations were more prominent in CM-MO when compared to EM participants (p = 0.001). miR-155 positively correlated with IL-1ß (p = 0.001) and TNF-α (p = 0.001) expression levels. Finally, in people with CM-MO, we described an up-regulated percentage of events in both M1 and M2 monocytic profiles. CONCLUSIONS: Our study shows for the first time a specific profile of activation of miR-155 gene expression levels in monocytes of selected migraine subpopulations, more pronounced in subjects with CM-MO. Interestingly, mir-155 expression correlated with markers of activation of the inflammatory and immune systems. The CM-MO subpopulation showed a peculiar increase of both pro-inflammatory and anti-inflammatory monocytes which worths further investigation. TRIAL REGISTRATION: www. CLINICALTRIALS: gov . (NCT05891808).

A Case of Anti-Ma2 Encephalitis Presenting with Pendular Torsional Nystagmus.

Antibodies against the neuronal protein Ma2 have been reported in a peculiar form of paraneoplastic encephalitis with prominent involvement of the limbic, brainstem, and diencephalic structures and usually associated with germ cell testicular, lung, or breast cancer. The diagnosis is frequently challenged by atypical clinical manifestations including parkinsonism, sleep disturbances, hypothalamic-pituitary dysfunctions, and motor neuron-like syndrome. In recent years, the advent of monoclonal antibodies targeting immune checkpoints has deeply changed the treatment of different tumors, especially melanoma and lung cancer. However, given their nature, an increasing number of neurological immune-related adverse events, including ocular motor abnormalities, have been described. Here, we report a woman with advanced non-small cell lung cancer treated with anti-PD-L1 durvalumab, presenting with an isolated pendular torsional nystagmus, in association with anti-Ma2 antibodies. This peculiar case widens our knowledge on the clinical presentation of anti-Ma2 encephalitis associated with checkpoint inhibitors.

Who cares about migraine? Pathways and hurdles in the European region - access to care III.

BACKGROUND: Migraine is a highly prevalent primary headache disorder and a leading cause of disability. Difficulties in access to care during diagnostic and therapeutic journey contribute to the disease burden. Several target-specific drugs have reached the market in the past four years and have modified the treatment paradigm in migraine. The aim of this study is to provide an updated snapshot of the pathways and hurdles to care for migraine in different European countries by directly asking patients. METHODS: In 2021 the European Migraine and Headache Alliance proposed a 39-item questionnaire that was administered online to an adult migraine population in European countries. Questions were focused on socio-demographic and migraine data, access to diagnosis and treatment, disease-related burden and the main channel for disease information. RESULTS: A total of 3169 questionnaires were returned from 10 European countries. Responders were predominantly females, age range 25-59 years, with a migraine history longer than 10 years in 82% of cases, and with at least 8 headache days per month in 57% of cases. Respondents reported limitations in social, working and personal life during both the ictal and interictal phase. The activities mostly impaired during the attacks were driving (55%), cooking or eating (42%), taking care of family/childcare (40%) and getting medicines at the pharmacy (40%). The most frequently reported unmet need was the long delay between the first visit and migraine diagnosis: 34% of respondents had to see ≥ 4 specialists before being correctly diagnosed, and between the diagnosis and treatment prescription: > 5 years in 40% of cases. The most relevant needs in terms of quality of life were the desire for a lower migraine frequency, an effective treatment and a greater involvement in society. CONCLUSIONS: Data from the present survey point to the existence and persistence of multiple hurdles that result in significant limitations to access to care and to the patients' social life. A close cooperation between decision makers, healthcare workers and patients is needed to overcome these barriers.

Oculo-vestibular signs in experimentally induced migraine attacks: an exploratory analysis.

Vestibular symptoms accompanying headache are quite common in migraine patients. Based on the association of vertigo with migraine, vestibular migraine was included in the appendix of the 3rd edition of the International Classification of Headache Disorders as a possible migraine subtype worthy of further investigation. In this post hoc, exploratory analysis, we investigated the occurrence of oculo-vestibular signs (OVSs) during experimentally induced migraine attacks in 24 episodic migraine patients and 19 healthy controls exposed to sublingual nitroglycerin (NTG - 0.9 mg). A comprehensive clinical examination was performed at baseline, at the onset of the migraine-like attack, and immediately before hospital discharge (180 minutes after NTG administration). Three of the 13 migraine patients who developed a spontaneous-like migraine attack during the hospital observation period (23.1%) also developed OVSs during the induction test. Noteworthy, none of the patients with a negative induction test developed OVSs and no OVSs were reported in healthy subjects at any time point. The exploratory nature of our study does not allow to draw definite conclusions on the possible implications of a vestibular dysfunction in migraine pathophysiology. Our results however suggest that NTG administration may lend itself to investigate vestibular dysfunction in migraine, at least in a subset of patients. The present findings represent a starting point for designing future ad hoc and well-powered studies.

Does MIDAS reduction at 3 months predict the outcome of erenumab treatment? A real-world, open-label trial.

BACKGROUND: In Italy, monoclonal antibodies targeting the CGRP pathway are subsidized for the preventive treatment of high frequency and chronic migraine (CM) in patients with a MIgraine Disability ASsessment (MIDAS) score ≥ 11. Eligibility to treatment continuation requires a ≥ 50% MIDAS score reduction at three months (T3). In this study, we evaluate whether a ≥ 50% MIDAS score reduction at T3 is a reliable predictor of response to one-year erenumab treatment. METHODS: In this prospective, open-label, real-world study, 77 CM patients were treated with erenumab 70-140 mg s.c. every 28 days for one year (T13). We collected the following variables: monthly migraine days (MMDs), monthly headache days (MHDs), days of acute medication intake, MIDAS, HIT-6, anxiety, depression, quality of life and allodynia. Response to erenumab was evaluated as: i) average reduction in MMDs during the 1-year treatment period; and ii) percentage of patients with ≥ 50% reduction in MMDs during the last 4 weeks after the 13th injection (RespondersT13). RESULTS: Erenumab induced a sustained reduction in MMDs, MHDs and intake of acute medications across the 12-month treatment period, with 64.9% of patients qualifying as RespondersT13. At T3, 55.8% of patients reported a ≥ 50% reduction in MIDAS score (MIDASRes) and 55.4% of patients reported a ≥ 50% reduction in MMDs (MMDRes). MIDASRes and MMDRes patients showed a more pronounced reduction in MMDs during the 1-year treatment as compared to NON-MIDASRes (MIDASRes: T0: 23.5 ± 4.9 vs. T13: 7.7 ± 6.2; NON- MIDASRes: T0: 21.6 ± 5.4 vs. T13: 11.3 ± 8.8, p = 0.045) and NON-MMDRes (MMDRes: T0: 23.0 ± 4.5 vs. T13: 6.6 ± 4.8; NON-MMDRes: T0: 22.3 ± 6.0 vs. T13: 12.7 ± 9.2, p < 0.001) groups. The percentage of RespondersT13 did not differ between MIDASRes (74.4%) and NON-MIDASRes (52.9%) patients (p = 0.058), while the percentage of RespondersT13 was higher in the MMDRes group (83.3%) when compared to NON-MMDRes (42.9%) (p = 0.001). MMDRes predicted the long-term outcome according to a multivariate analysis (Exp(B) = 7.128; p = 0.001), while MIDASRes did not. Treatment discontinuation based on MIDASRes would have early excluded 36.0% of RespondersT13. Discontinuation based on "either MIDASRes or MMDRes" would have excluded a lower percentage (16%) of RespondersT13. CONCLUSION: MIDASRes only partly reflects the 12-month outcome of erenumab treatment in CM, as it excludes more than one third of responders. A criterion based on the alternative consideration of ≥ 50% reduction in MIDAS score or MMDs in the first three months of treatment represents a more precise and inclusive option. TRIAL REGISTRATION: The trial was retrospectively registered at www. CLINICALTRIALS: gov (NCT05442008). CGRP: Calcitonin Gene Related Peptide. MIDAS: MIgraine Disability Assessment. MMDs: monthly migraine days. MIDASRes: Patients with a MIDAS score reduction of at least 50% at T3. MMDRes: Patients with a MMDs reduction of at least 50% at T3. ResponderT13: Patients with a MMDs reduction from baseline of at least 50% in the last 4 weeks of observation period (after 13 erenumab administrations). T0: First erenumab administration. T3, T6, T9, T12: Follow-up visits at three, six, nine, and twelve months after first erenumab administration. T13: Last visit of the protocol.

COVID-19 in patients with myasthenia gravis: Epidemiology and disease course.

INTRODUCTION/AIMS: Coronavirus disease 2019 (COVID-19), a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has become a global pandemic. Patients with myasthenia gravis (MG), often treated with immunosuppressants, might be at higher risk of developing COVID-19 and of demonstrating a severe disease course. We aimed to study prevalence and describe features of COVID-19 in MG patients. METHODS: In May 2020, we conducted telephonic interviews with MG patients followed at our referral center. We collected structured data regarding MG and COVID-19, which was diagnosed as probable or confirmed according to the European Centre for Disease Prevention and Control case definition. We compared confirmed-COVID-19 prevalence calculated from the beginning of the pandemic in MG patients with that of the overall Pavia district. RESULTS: We interviewed 162 MG patients (median age, 66 y; interquartile range 41-77; males 59.9%), 88 from the Pavia district. Three patients had SARS-CoV-2-confirmed by polymerase chain reaction and eight had probable-COVID-19. In the Pavia district, the prevalence of confirmed-COVID-19 among MG patients (1/88, 1.14%) and overall population (4777/546 515, 0.87%) did not differ (P = .538). Higher Myasthenia Gravis Foundation of America clinicalclass and the need for recent rescue treatment, but not ongoing immunosuppressive treatments, were associated with COVID-19 risk. Of 11 MG patients with probable/confirmed-COVID-19, 3 required ventilator support, and 2 elderly patients died of COVID-19 respiratory insufficiency. Only 1 of11 patients experienced worsening MG symptoms, which improved after increasing their steroid dose. DISCUSSION: The risk of COVID-19 in MG patients seems to be no higher than that of the general population, regardless of immunosuppressive therapies. In our cohort, COVID-19 barely affected MG course.

Psychological predictors of negative treatment outcome with Erenumab in chronic migraine: data from an open label long-term prospective study.

BACKGROUND: Monoclonal antibodies (mABs) targeting the calcitonin gene-related peptide (CGRP) pathway represent the first disease-specific preventive migraine therapy. Growing evidence suggests that they are effective in the preventive treatment of difficult-to-treat patients. In this study, we evaluated the psychological predictors of the outcome of treatment with the anti-CGRP monoclonal antibody erenumab in patients with chronic migraine (CM). METHODS: Seventy-five patients with CM who had already failed at least 3 preventive therapies received erenumab every 28 days for a period of 12 months. Before the first administration, patients received a full psychological evaluation using The Structured Clinical Interview for DSM-5 Clinician Version (SCID-5-CV) to assess personality disturbances (primary outcome), mood and anxiety disorders, and as well specific questionnaires to evaluate alexithymia traits, childhood traumas, and current stressors (secondary outcomes). RESULTS: After 12 months of treatment, 53 patients reported a reduction of at least 50% in headache days/per month (Responders), whereas 22 did not (Non Responders). When compared to Responders, Non Responders were characterized by a higher prevalence of personality disorders belonging to Cluster C (avoidant, dependent, and obsessive-compulsive) (77% vs 37%, p = .001). Non Responders were also characterized by a higher prevalence of anxiety disorders (90% vs 60%, p = 0.007), showed more alexithymic traits (51.7 ± 13.7 vs 42.9 ± 14.3, p = 0.017), and reported a higher number of 'at least serious' current stressors (3.2 ± 4.0 vs 0.8 ± 1.4, p < .0001) than Responders. At the multivariate analysis, higher prevalence of Cluster C personality disorders (OR 3.697; p = 0.05) and higher number of 'at least serious' life events (OR 1.382; p = 0.017) arose as prognostic factors of erenumab failure. CONCLUSIONS: Erenumab confirmed its effectiveness in a population of difficult-to-treat migraine. The presence of "anxious-fearful" personality together with current stressors and anxiety represent negative predictors of treatment outcome. TRIAL REGISTRATION: The study protocol was registered at clinicaltrials.gov ( NCT04361721 ).

Direct antivirals and cognitive impairment in hepatitis C: a clinical-neurophysiologic study.

Cognition was assessed in hepatitis C virus (HCV) patients, who did not meet the criteria for a minimal hepatic encephalopathy. Their liver function was compensated. We then disentangled potential cognitive changes associated with a sustained virologic response at 12 weeks (SVR-12), following treatment with direct antiviral agents (DAAs). We studied 23 selected HCV patients with a battery of standard neuropsychological tests, and with recordings of the P300 wave, a cerebral potential of "cognitive" significance. There was a baseline evaluation (T0) and a second one 6 months later (T1). We had 2 control groups of comparable age and sex, i.e., 15 patients suffering from non-alcoholic fatty liver disease (NAFLD) and 15 healthy subjects. At T0, we detected a significant (p < 0.05) cognitive impairment in the HCV group, which involved episodic and working memory, attention, visuospatial and verbal abilities, executive functions, and logic reasoning. The P300 latency was significantly (p < 0.05) delayed in the group. At T1, we observed some significant (p < 0.05) HCV recovery in given test domains, e.g., memory, executive functions, and reasoning. Accordingly, the P300 latency shortened significantly (p < 0.05). HCV patients exhibited subtle cognitive defects, somehow independent of their liver condition, possibly linked to direct or indirect brain involvement by the virus. These defects partly recovered following the SVR-12, as achieved through DAAs. The P300 wave was a valid neurophysiologic counterpart of these changes. DAAs can have a role in the early preservation of cognition in HCVs.

The role of stroke-induced immunosuppression as a predictor of functional outcome in the neurorehabilitation setting.

Stroke affects the interconnection between the nervous and immune systems, leading to a down-regulation of immunity called stroke-induced immunosuppression (SII). The primary aim of this study is to investigate SII role as a predictor of functional, neurological, and motor outcomes in the neurorehabilitation setting (NRB). We conducted a prospective observational study enrolling post-acute stroke patients hospitalized for neurorehabilitation. At NRB admission (T0) and discharge (T1), we assessed presence of SII (defined by a neutrophil-to-lymphocyte ratio ≥ 5) and we evaluated functional independence (Functional Independence Measure-FIM, Barthel Index-BI), motor performances (Tinetti Score, Hauser Ambulation Index) and neurological impairment (NIHSS). We enrolled 96 patients (45.8% females, 70.6 ± 13.9 years, 88.5% ischemic stroke). At T0, 15.6% of patients (15/96) had SII. When compared to immunocompetent patients (IC), the SII group was characterized by worse baseline functional independence, motor performances and neurological disability. The same was confirmed at T1 (FIM p = 0.012, BI p = 0.007, Tinetti p = 0.034, NIHSS p = 0.001). Neurological disability demonstrated a less pronounced improvement in SII (ΔNIHSS: SII: - 2.1 ± 2.3 vs. IC: - 3.1 ± 2.5, p = 0.035). SII group presented a higher percentage of infectious complications during the neurorehabilitation period (SII 80% vs. IC 25.9%; p = 0.001). SII may represent a negative prognostic factor in the neurorehabilitation setting. SII patients were characterized by poorer functional, motor, neurological performances and higher risk of infectious complications. ClinicaTrial registration: NCT05889169.

Searching for the Predictors of Response to BoNT-A in Migraine Using Machine Learning Approaches.

OnabotulinumtoxinA (BonT-A) reduces migraine frequency in a considerable portion of patients with migraine. So far, predictive characteristics of response are lacking. Here, we applied machine learning (ML) algorithms to identify clinical characteristics able to predict treatment response. We collected demographic and clinical data of patients with chronic migraine (CM) or high-frequency episodic migraine (HFEM) treated with BoNT-A at our clinic in the last 5 years. Patients received BoNT-A according to the PREEMPT (Phase III Research Evaluating Migraine Prophylaxis Therapy) paradigm and were classified according to the monthly migraine days reduction in the 12 weeks after the fourth BoNT-A cycle, as compared to baseline. Data were used as input features to run ML algorithms. Of the 212 patients enrolled, 35 qualified as excellent responders to BoNT-A administration and 38 as nonresponders. None of the anamnestic characteristics were able to discriminate responders from nonresponders in the CM group. Nevertheless, a pattern of four features (age at onset of migraine, opioid use, anxiety subscore at the hospital anxiety and depression scale (HADS-a) and Migraine Disability Assessment (MIDAS) score correctly predicted response in HFEM. Our findings suggest that routine anamnestic features acquired in real-life settings cannot accurately predict BoNT-A response in migraine and call for a more complex modality of patient profiling.