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Abstract Background Randomized clinical trials have demonstrated efficacy and safety of erenumab. The aim of this study is to evaluate the effectiveness and safety of erenumab in a real-world setting in French patients with migraine associated with extreme unmet needs. Methods This is a one year-prospective real-word study with enrolment of all consecutive adult patients included in the FHU InovPain registry who participated in a compassionate erenumab use program. Results Of 144 patients included, 140 patients (82.1% female / mean age of 50.9 ± 11.4) received at least one dose of erenumab and were concerned by effectiveness and safety assessment. All patients had failed 11 oral preventive treatments. Most of them suffered from chronic migraine (88.6%) and presented a medication overuse (90.7%) at baseline. Thirty-eight (27.1%) discontinued treatment during the 12-month follow-up, with 22 (15.7%), 11 (7.9%) and 5 (3.6%) patients before 3, 6 or 9 months of treatment. The proportion of ≥ 50% responders at M3, M6, M9 and M12 was 74/140 (52.9%), 69/118 (58.5%), 61/107 (57.0%) and 60/102 (58.8%) respectively. At M3, the rate of reversion from chronic migraine to episodic migraine was 57.3% and the rate of transition from medication overuse to non-overuse was 46.5%. For monthly migraine days, the median (IQR) was 18.0 (13.0–26.0), 9.0 (5.0–17.0), 7.5 (5.0–14.0), 8.0 (5.0–12.5) and 8.0 (5.0–12.0) at M0, M3, M6, M9 and M12 respectively. For HIT-6 score, the median (IQR) was 68.0 (63.8–73.3), 60.0 (54.0–65.0), 60.0 (50.3–53.0), 59.0 (50.0–63.0) and 58.0 (50.0–62.9) at M0, M3, M6, M9 and M12 respectively. Fifty-three (37.9%) patients reported at least one of the following adverse events: cutaneous erythema and/or pain at the injection site for 42 (30%) patients, constipation for 22 (15.7%) patients, muscle spasm for 2 (1.4%) patients, alopecia for one (0.7%) patient and blood pressure increase in one (0.7%) patient. There was no serious adverse event. One female patient became pregnant after 5 months of exposure to erenumab with a safe evolution after treatment discontinuation. Conclusion This first French real-world study related to migraine prevention with CGRP-mAbs confirms effectiveness and safety of erenumab in patients with extreme unmet needs.

Abstract Background Preliminary evidence suggests that several headache disorders may be associated with glymphatic dysfunction. However, no studies have been conducted to examine the glymphatic activity in migraine chronification. Purposes To investigate the glymphatic activity of migraine chronification in patients with episodic migraine (EM) and chronic migraine (CM) using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) method. Methods In this cross-sectional study, patients with EM, CM, and healthy controls (HCs) were included. All participants underwent a standard brain magnetic resonance imaging (MRI) examination. Bilateral DTI-ALPS indexes were calculated for all participants and compared among EM, CM, and HC groups. Correlations between the DTI-ALPS index and clinical characteristics were analyzed. Results A total of 32 patients with EM, 24 patients with CM, and 41 age- and sex-matched HCs were included in the analysis. Significant differences were found in the right DTI-ALPS index among the three groups (p = 0.011), with CM showing significantly higher values than EM (p = 0.033) and HCs (p = 0.015). The right DTI-ALPS index of CM group was significantly higher than the left DTI-ALPS index (p = 0.005). And the headache intensity was correlated to DTI-ALPS index both in the left hemisphere (r = 0.371, p = 0.011) and in the right hemisphere (r = 0.307, p = 0.038), but there were no correlations after Bonferroni correction. Conclusions Glymphatic system activity is shown to be increased instead of impaired during migraine chronification. The mechanism behind this observation suggests that increased glymphatic activity is more likely to be a concomitant phenomenon of altered vascular reactivity associated with migraine pathophysiology rather than a risk factor of migraine chronification.

Abstract Background Amygdala, an essential element of the limbic system, has served as an important structure in pain modulation. There is still a lack of clarity about altered cerebral perfusion of amygdala in migraine. This study aimed to investigate the perfusion variances of bilateral amygdala in episodic migraine (EM) and chronic migraine (CM) using multi-delay pseudo-continuous arterial spin-labeled magnetic resonance imaging (pCASL-MRI). Methods Twenty-six patients with EM, 55 patients with CM (33 CM with medication overuse headache (MOH)), and 26 age- and sex-matched healthy controls (HCs) were included. All participants underwent 3D multi-delay pCASL MR imaging to obtain cerebral perfusion data, including arrival-time-corrected cerebral blood flow (CBF) and arterial cerebral blood volume (aCBV). The CBF and aCBV values in the bilateral amygdala were compared among the three groups. Correlation analyses between cerebral perfusion parameters and clinical variables were performed. Results Compared with HC participants, patients with CM were found to have increased CBF and aCBV values in the left amygdala, as well as increased CBF values in the right amygdala (all P 0.05). In patients with CM, the increased perfusion parameters of bilateral amygdala were positively correlated with MIDAS score after adjustments for age, sex, and body mass index (BMI). Conclusion Hyperperfusion of bilateral amygdala might provide potential hemodynamics evidence in the neurolimbic pain network of CM.

Abstract To determine specific resting-state network patterns underlying alterations in chronic migraine, we employed oscillatory connectivity and machine learning techniques to distinguish patients with chronic migraine from healthy controls and patients with other pain disorders. This cross-sectional study included 350 participants (70 healthy controls, 100 patients with chronic migraine, 40 patients with chronic migraine with comorbid fibromyalgia, 35 patients with fibromyalgia, 30 patients with chronic tension-type headache, and 75 patients with episodic migraine). We collected resting-state magnetoencephalographic data for analysis. Source-based oscillatory connectivity within each network, including the pain-related network, default mode network, sensorimotor network, visual network, and insula to default mode network, was examined to determine intrinsic connectivity across a frequency range of 1–40 Hz. Features were extracted to establish and validate classification models constructed using machine learning algorithms. The findings indicated that oscillatory connectivity revealed brain network abnormalities in patients with chronic migraine compared with healthy controls, and that oscillatory connectivity exhibited distinct patterns between various pain disorders. After the incorporation of network features, the best classification model demonstrated excellent performance in distinguishing patients with chronic migraine from healthy controls, achieving high accuracy on both training and testing datasets (accuracy > 92.6% and area under the curve > 0.93). Moreover, in validation tests, classification models exhibited high accuracy in discriminating patients with chronic migraine from all other groups of patients (accuracy > 75.7% and area under the curve > 0.8). In conclusion, oscillatory synchrony within the pain-related network and default mode network corresponded to altered neurophysiological processes in patients with chronic migraine. Thus, these networks can serve as pivotal signatures in the model for identifying patients with chronic migraine, providing reliable and generalisable results. This approach may facilitate the objective and individualised diagnosis of migraine.

BackgroundReal-world studies have shown the sustained therapeutic effect and favourable safety profile of OnabotulinumtoxinA (BoNTA) in the long term and up to 4 years of treatment in chronic migraine (CM). This study aims to assess the safety profile and efficacy of BoNTA in CM after 5 years of treatment in a real-life setting.MethodsWe performed a retrospective chart review of patients with CM in relation to BoNTA treatment for more than 5 years in 19 Spanish headache clinics. We excluded patients who discontinued treatment due to lack of efficacy or poor tolerability.Results489 patients were included [mean age 49, 82.8% women]. The mean age of onset of migraine was 21.8 years; patients had CM with a mean of 6.4 years (20.8% fulfilled the aura criteria). At baseline, patients reported a mean of 24.7 monthly headache days (MHDs) and 15.7 monthly migraine days (MMDs). In relation to effectiveness, the responder rate was 59.1% and the mean reduction in MMDs was 9.4 days (15.7 to 6.3 days; p

ObjectiveThis real-world study aimed to investigate how onabotulinumtoxinA affects the outcome of migraine, along with accompanying anxiety, depression, and bruxism among a group of patients with chronic migraine (CM) and define predictors of good response.MethodsPatients diagnosed with CM who received onabotulinumtoxinA were included in this single-center, real-world retrospective cohort study. Monthly headache days (MHDs), monthly migraine days (MMDs), headache intensity (numeric rating scale-NRS) and headache characteristics were evaluated at baseline and 12 weeks post-treatment. Patient-reported outcome measures (PROMs) included Migraine Disability Assessment Scale (MIDAS), Headache Impact Test-6 (HIT-6) scores, 12-item Allodynia Symptom Checklist (ASC-12), Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI). Response to onabotulinumtoxinA (% reduction in MHDs) and treatment-related adverse events (TRAEs) were also evaluated. OnabotulinumA was applied to the masseter muscles in patients complaining of bruxism.ResultsA total of 72 patients (mean ± SD age: 36.3 ± 8.5 years; 91.7% were female) diagnosed with CM were included. OnabotulinumtoxinA revealed significant decrease in median (IQR) MHDs [from 20(15–25) at baseline to 6(4–10), p

Background: Chronic periodontitis (CP) is a chronic inflammatory disease, primarily caused by microbial infections and characterized by immune system dysfunction. The latter ultimately leads to the progressive destruction of the alveolar bone supporting the teeth in the jawbones. Chronic migraine (CM) is a complex disorder characterized by repetitive episodes of moderate to severe headaches that unfold over hours to days. The episodes are usually unilateral and generally associated with nausea and light and/or sound stimuli sensitivity. The disease is a common cause of disability and loss of working hours, as it significantly burdens the patient's daily life. CP and CM association is clinically relevant as both involve inflammatory mechanisms and immune dysfunction. Aim: To systematically review the literature on the epidemiological association between CP and CM in adults. Methods: The study protocol followed the PRISMA 2020 statement. The design of the study adhered to the Cochrane methodology. A comprehensive literature search was conducted in PubMed, Scopus, and Cochrane databases, as well as a manual search and evaluation of gray literature sources. The Review Manager (RevMan) 5.4 software was used for the meta-analysis. The effect size of the outcome was expressed as odds ratio (OR) with a 95 % confidence interval (CI), providing a measure of the association between CP and CM. The Chi-square test and I2 statistic were employed to assess heterogeneity among the included studies. The inclusion criteria were English language, observational (case-control) design, and report of the diagnostic criteria for CP and CM. Duplicate entries were excluded. The reliability and quality of the included studies were assessed using the Newcastle-Ottawa Scale (NOS) and GRADE tools. Two independent reviewers performed all evaluations and a third resolved discrepancies. Results: The meta-analysis included three observational studies with 522 participants. CM patients were 2.82 times more likely to be diagnosed with CP compared with healthy controls. This association was statistically significant (OR 2.82, 95 % CI 1.96–4.05, p < 0.0001); however, the external generalizability is limited because of the examination of data originating from populations with specific ethnic backgrounds. Conclusion: A high prevalence of CP was found among patients with CM compared with healthy controls. Healthcare professionals should be aware of the correlation between these pathological conditions to provide patients with high-quality care through an effective and comprehensive diagnostic and therapeutic approach.

Background: Migraine has a negative impact on patients’ quality of life, with the frequency of attacks being associated with greater disability and poorer health status. Frequent migraine-type headaches require prophylactic treatment, which has so far been of limited effectiveness until advent of calcitonin gene-related peptide (CGRP) monoclonal antibody.Materials and Methods: A prospective analysis was conducted of data from 41 migraine patients who experienced 4 or more monthly migraine days (MMD) longer than three months. At the beginning of the study, treatment with monoclonal antibodies against CGRP (fremanezumab 225 mg or erenumab 70 or 140 g per month) was prescribed according to the indications. The effect of the medications was evaluated after 3-month period.Results: The mean age of patients was 37.17 (±11.78) years. It was found that 17 patients (41.5%) had episodic migraine (EM) and 24 (58.5%) had chronic migraine (CM). Fremanezumab was prescribed to 26 patients (63.4%) and erenumab to 15 patients (36.6%); among the latter, 13 patients used 70 mg/month and 2 patients used 140 mg/month. Three months after treatment, CM changed to EM for 19 patients (79.2%), 27 patients (65.9%) had ≥50% reduction in the number of MMD and total migraine disability assessment (MIDAS) score was reduced by >50% in 31 patients (75.6%). Also, all areas of quality of life of patients were improved after 3 months continued treatment compared to baseline.Conclusions: For more than half the patients using fremanezumab or erenumab after 3-month period, MMD decreased by ≥50% and total MIDAS score by >50 points. All areas of quality of life were improved after prophylactic treatment of migraine.

IntroductionCalcitonin gene-related peptide (CGRP) plays an important role in cerebral vasodilation, so here we aim to quantify the impact of CGRP monoclonal antibody (mAb) therapy on cerebral hemodynamics.MethodsIn 23 patients with chronic and episodic migraine, cerebral hemodynamic monitoring was performed (1) prior to and (2) 3-months into CGRP-mAb therapy. Transcranial Doppler monitored cerebral blood flow velocity (CBFv) in the middle cerebral artery (MCA) and posterior cerebral artery (PCA), from which cerebrovascular reactivity (CVR) and cerebral autoregulation (CA; Mx-index) were calculated.ResultsCA was similar off and on treatment, in the MCA (p = 0.42) and PCA (p = 0.72). CVR was also unaffected by treatment, in the MCA (p = 0.38) and PCA (p = 0.92). CBFv and blood pressure were also unaffected. The subgroup of clinical responders (>50% reduction in migraine frequency) exhibited a small reduction in MCA-CBFv (6.0 cm/s; IQR: 1.1–12.4; p = 0.007) and PCA-CBFv (8.9 cm/s; IQR: 6.9–10.3; p = 0.04).DiscussionDynamic measures of cerebrovascular physiology were preserved after 3 months of CGRP-mAb therapy, but a small reduction in CBFv was observed in patients who responded to treatment. Subgroup findings should be interpreted cautiously, but further investigation may clarify if CBFv is dependent on the degree of CGRP inhibition or may serve as a biomarker of drug sensitivity.

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Theory of Mind (ToM) is the ability to infer one's own and others' mental states. Growing research indicates that ToM is impaired in Chronic Migraine with Medication Overuse (CM + MO). However, the research in this field has been conducted using static scenario-based tasks, often failing to test mentalization in everyday situations and measuring only performance accuracy. We filled this gap by administering the Movie for the Assessment of Social Cognition (MASC) to subjects with CM + MO compared to episodic migraine (EM). This test allows us to assess both affective and cognitive ToM and which, in addition to being accurate, also analyzes the type of error in attribution of mental states, distinguishing between hypo-mentalization and hyper-mentalization. Thirty patients suffering from CM + MO and 42 from EM were enrolled. Results showed that CM + MO patients were less accurate in mental state attribution than EM. In addition, compared to EM, CM + MO individuals were more impaired in the affective ToM dimensions and committed more errors of hypo-mentalization. In conclusion, the application of MASC in patients with CM + MO allowed for the detection of an alteration in their ability to correctly draw conclusions about other people's mental states. This latter contributes critically to appropriate social reactions and also, possibly, to satisfactory social interactions. [ABSTRACT FROM AUTHOR]

Eptinezumab, a monoclonal antibody that targets calcitonin gene-related peptide (CGRP), was recently approved in Europe for the prophylactic treatment of migraine in adults who have at least four migraine days a month. Eptinezumab is administered by intravenous infusion every 12 weeks. During recent months, a considerable amount of evidence from eptinezumab trials has been published. The aim of this review is to describe the existing evidence on the tolerability, safety and efficacy of eptinezumab in patients with migraine. Data from randomized (PROMISE-1, PROMISE-2, RELIEF and DELIVER) and open-label (PREVAIL) phase 3 clinical trials have demonstrated the favorable effect of eptinezumab in migraine symptoms from first day of treatment. These studies showed that eptinezumab results in an overall reduction in mean monthly migraine days (MMDs), increases in the =50% and = 75% migraine responder rates (MRRs) and improvements in patient-reported outcome measures in both patients with episodic migraine (EM) and with chronic migraine (CM), including patients who failed previous preventive treatments. The RELIEF trial also showed that eptinezumab, within 2 h of administration, reduced headache pain, migraineassociated symptoms and acute medication use when administered during a migraine attack. Eptinezumab benefits manifested as early as day 1 after dosing and with the subsequent doses lasted up to at least 2 years. Treatment-emergent adverse events reported by =2% of patients included upper respiratory tract infection and fatigue. Current evidence demonstrates that eptinezumab has a potent, fast-acting, sustained migraine preventive effect in patients with EM and CM. Eptinezumab has also shown to be well tolerated, supporting its use in the treatment of patients with migraine and inclusion in the current migraine therapeutic options. [ABSTRACT FROM AUTHOR]

Background: The reimbursement of erenumab in Spain and other European countries is currently restricted because of the cost of this novel therapy to patients with migraine who have experienced previous failures to traditional preventive treatments. However, this reimbursement policy should be preferably based on cost-effectiveness studies, among other criteria. This study performed a cost-effectiveness analysis of erenumab versus topiramate for the prophylactic treatment of episodic migraine (EM) and versus placebo for chronic migraine (CM). Methods: A Markov model with a 10-year time horizon, from the perspective of the Spanish National Healthcare System, was constructed based on data from responder and non-responder patients. A responder was defined as having a minimum 50% reduction in the number of monthly migraine days (MMD). A hypothetical cohort of patients with EM with one or more prior preventive treatment failures and patients with CM with more than two treatment failures was considered. The effectiveness score was measured as an incremental cost per quality-adjusted life year (QALY) gained and cost per migraine day (MD) avoided. Data from clinical outcomes and patient characteristics were obtained from erenumab clinical trials (NCT02066415, STRIVE, ARISE, LIBERTY and HER-MES). Deterministic and probabilistic sensitivity analyses were performed to validate the robustness of the model. Results: After a 10-year follow-up, the estimated QALYs were 5.88 and 6.11 for patients with EM treated with topiramate and erenumab, respectively. Erenumab showed an incremental cost per patient of €4,420 vs topiramate. For CM patients, erenumab resulted in 0.756 QALYs gained vs placebo; and an incremental cost of €1,814. Patients treated with erenumab achieved reductions in MD for both EM and CM (172 and 568 MDs, respectively). The incremental cost per QALY gained with erenumab was below the Spanish threshold of €30,000/QALY for both health and societal perspectives (EM €19,122/QALY and CM €2,398/QALY). Conclusions: Erenumab is cost-effective versus topiramate as a preventive treatment for EM and versus placebo for patients with CM from the perspective of the Spanish National Health System. [ABSTRACT FROM AUTHOR]

Introduction: The efficiency of The International Classification of Headache Disorders (ICHD-3) in reflecting patients' disability has recently been questioned. This prompts consideration that clinical features beyond pain may more accurately indicate the extent of underlying brain impairment than the mere frequency of headache days. Important cognitive dysfunctions and psychological impairment have been reported in burdensome cases of migraine, and the presence of these alterations has been associated with biological changes in the nervous system. This study aimed to compare migraine-related disability within a specific patient group, classified using ICHD-3 criteria or classified based on findings from a neuropsychological evaluation using machine learning. Additionally, a complementary voxel-based morphometry (VBM) comparison was conducted to explore potential neuroanatomical differences between the resulting groups. Patients and methods: The study included episodic and chronic migraine patients seeking consultation at a specialized headache department. A neuropsychological evaluation protocol, encompassing validated standardized tests for cognition, anxiety, depression, perceived stress, and headache-related impact (HIT-6) and disability (MIDAS), was administered. Results from this evaluation were input into an automated K-means clustering algorithm, with a predefined K=2 for comparative purposes. A supplementary Voxel-based Morphometry (VBM) evaluation was conducted to investigate neuroanatomical contrasts between the two distinct grouping configurations. Results: The study involved 111 participants, with 49 having chronic migraine and 62 having episodic migraine. Seventy-four patients were assigned to cluster one, and 37 patients were assigned to cluster two. Cluster two exhibited significantly higher levels of depression, anxiety, and perceived stress, and performed worse in alternating and focalized attention tests. Differences in HIT-6 and MIDAS scores between episodic and chronic migraine patients did not reach statistical significance (HIT-6: 64.39 (±7,31) vs 62.92 (±11,61); p= 0. 42 / MIDAS: 73.63 (±68,61) vs 84.33 (±63,62); p=0.40). In contrast, patients in cluster two exhibited significantly higher HIT-6 (62.32 (±10,11) vs 66.57 (±7,21); p=0.03) and MIDAS (68.69 (±62,58) vs 97.68 (±70,31); p=0.03) scores than patients in cluster one. Furthermore, significant differences in grey matter volume between the two clusters were noted, particularly involving the precuneus, while differences between chronic and episodic migraine patients did not withstand correction for multiple comparisons. Conclusions: The classification of migraine patients based on neuropsychological characteristics demonstrates a more effective separation of groups in terms of disability compared to categorizing them based on the chronic or episodic diagnosis of ICHD-3. These findings could reveal biological changes that might explain differences in treatment responses among apparently similar patients. [ABSTRACT FROM AUTHOR]

Background: Energy metabolism disorders and neurogenic inflammation play important roles in the central sensitization to chronic migraine (CM). AMP-activated protein kinase (AMPK) is an intracellular energy sensor, and its activation regulates inflammation and reduces neuropathic pain. However, studies on the involvement of AMPK in the regulation of CM are currently lacking. Therefore, this study aimed to explore the mechanism underlying the involvement of AMPK in the central sensitization to CM. Methods: Mice with recurrent nitroglycerin (NTG)-induced CM were used to detect the expression of AMPK protein in the trigeminal nucleus caudalis (TNC). Following intraperitoneal injection of the AMPK activator 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR) and inhibitor compound C, the mechanical pain threshold, activity level, and pain-like behaviors in the mice were measured. The expression of calcitonin gene-related peptide (CGRP) and cytokines, M1/M2 microglia, and NF-κB pathway activation were detected after the intervention. Results: Repeated NTG injections resulted in a gradual decrease in AMPK protein expression, and the negative regulation of AMPK by increased ubiquitin-like plant homeodomain and RING finger domain 1 (UHRF1) expression may counteract AMPK activation by increasing ADP/ATP. AICAR can reduce the hyperalgesia and pain-like behaviors of CM mice, improve the activity of mice, reduce the expression of CGRP, IL-1β, IL-6, and TNF-α in the TNC region, and increase the expression of IL-4 and IL-10. Moreover, AMPK in TNC was mainly located in microglia. AICAR could reduce the expression of inducible NO synthase (iNOS) in M1 microglia and increase the expression of Arginase 1 (Arg1) in M2 microglia by inhibiting the activation of NF-κB pathway. Conclusions: AMPK was involved in the central sensitization of CM, and the activation of AMPK reduced neuroinflammation in NTG-induced CM mice. AMPK may provide new insights into interventions for energy metabolism disorders and neurogenic inflammation in migraine. [ABSTRACT FROM AUTHOR]

The article focuses on investigating clinical outcomes among youth with continuous headache, revealing improvements in headache status within 3–4 months after receiving multidisciplinary treatment, despite moderate average headache severity. It is discussed that treatment utilization shifted towards increased use of pill-based preventive treatments and decreased engagement in nonpharmacologic strategies, highlighting potential treatment preferences and priorities among this population.

Background: Women show increased prevalence and severity of migraine compared to men. Whether small molecule calcitonin gene-related peptide receptor (CGRP-R) antagonists (i.e., gepants) and monoclonal antibodies targeting either the CGRP-R or the CGRP peptide might show sexually dimorphic outcomes for acute and preventive therapy has not been established. Methods: We conducted a subpopulation analysis of available published data from FDA reviews to evaluate potential sex differences in the response rates of ubrogepant, rimegepant and zavegepant for acute migraine therapy. Available data from FDA reviews of erenumab, fremanezumab, galcanezumab and eptinezumab, approved CGRP-R and CGRP monoclonal antibodies and of atogepant were examined for prevention outcomes based on patient sex. Preventive outcomes were analyzed separately for patients with episodic migraine and chronic migraine. Results: In women, the three approved gepants produced statistically significant drug effects regardless of dose tested on the FDA mandated co-primary endpoints, the proportion of patients achieving two-hour pain-freedom and the proportion of patients free of their most bothersome symptom at two hours post-dose. In women, the average placebo-subtracted two-hour pain-freedom proportion was 9.5% (CI: 7.4 to 11.6) and the average numbers needed to treat was 11. The free from most bothersome symptom at two hours outcomes were also significant in women. The gepant drugs did not reach statistically significant effects on the two-hour pain-freedom endpoint in the men, with an average drug effect of 2.8% (CI: −2.5 to 8.2) and an average number needed to treat of 36. For freedom from most bothersome symptom at two hours post-dose endpoint, differences were not significant in male patients. The treatment effect in each of the gepant studies was always numerically greater in women than in men. In evaluation of prevention outcomes with the antibodies or atogepant using the change from the specified primary endpoint (e.g., monthly migraine days), the observed treatment effect for episodic migraine patients almost always favored drug over placebo in both women and men. For chronic migraine patients the treatment effects of antibodies were similar in men and women and always favored the drug treated group. Conclusion/Interpretation: Small molecule CGRP-R antagonists are effective in acute migraine therapy in women but available data do not demonstrate effectiveness in men. CGRP-targeting therapies are effective for migraine prevention in both male and female episodic migraine patients but possible sex differences remain uncertain. In male and female chronic migraine patients, CGRP/CGRP-R antibodies were similarly effective. The data highlight possible differential effects of CGRP targeted therapies in different patient populations and the need for increased understanding of CGRP neurobiology in men and women. [ABSTRACT FROM AUTHOR]

Background: Migraine is a disabling neurologic disease that can fluctuate over time in severity, frequency, and acute medication use. Harris Poll Migraine Report Card was a US population-based survey to ascertain quantifiable distinctions amongst individuals with current versus previous high-frequency headache/migraine and acute medication overuse (HFM+AMO). The objective of this report is to compare self-reported experiences in the migraine journey of adults with HFM+AMO to those who previously experienced HFM+AMO but currently have a sustained reduction in headache/migraine frequency and acute medication use. Methods: An online survey was available to a general population panel of adults (≥18 years) with migraine per the ID Migraine™ screener. Respondents were classified into "current HFM+AMO" (within the last few months had ≥8 headache days/month and ≥10 days/month of acute medication use; n=440) or "previous HFM+AMO" (previously had HFM+AMO, but within the last few months had ≤7 headache days/month and ≤9 days/month of acute medication use; n=110). Survey questions pertained to demographics, diagnosis, living with migraine, healthcare provider (HCP) communication, and treatment. Results: Participants in the current HFM+AMO group had 15.2 monthly headache days and 17.4 days of monthly acute medication use in last few months compared to 4.2 and 4.1 days for the previous HFM+AMO group, respectively. Overall, current preventive pharmacologic treatment use was low (15-16%; P>0.1 for current vs previous) in both groups. Previous HFM+AMO respondents reported better current acute treatment optimization. More respondents with current (80%) than previous HFM+AMO (66%) expressed concern with their current health (P<0.05). More than one-third of both groups wished their HCP better understood their mental/emotional health (current 37%, previous 35%; P>0.1 for current vs previous) and 47% (current) to 54% (previous) of respondents worried about asking their HCP too many questions (P>0.1 for current vs previous). Conclusion: Apart from optimization of acute medication, medical interventions did not significantly differentiate between the current and previous HFM+AMO groups. Use of preventive pharmacological medication was low in both groups. Adults with current HFM+AMO more often had health concerns, yet both groups expressed concerns of disease burden. Optimization of acute and preventive medication and addressing mental/emotional health concerns of patients are areas where migraine care may impact outcomes regardless of their disease burden. [ABSTRACT FROM AUTHOR]

Objective: Medication overuse headache (MOH) was recently shown to be associated with leaky gut in rodents. We aimed to investigate whether chronic migraine (CM) patients with MOH have elevated lipopolysaccharide levels and inflammatory molecules in blood circulation. Materials and methods: The study included women participants (40 CM patients with NSAID overuse headache, 35 episodic migraine (EM) patients, and 20 healthy non-headache sufferers). Migraine duration, monthly migraine headache days, MigSCog, HADS-D, HADS-A, and HIT-6 scores were recorded. Serum samples were collected to measure circulating LPS, LPS binding protein (LBP), tight junction protein occludin, adherens junction protein vascular endothelial cadherin (VE-cadherin), CGRP, HMGB1, HIF-1α, IL-6, and IL-17 levels. Results: Serum LPS, VE-Cadherin, CGRP, HIF-1α, and IL-6 levels were significantly higher in the CM + MOH group compared to the EM group and healthy controls while serum LBP and HMGB1 were higher in the CM + MOH group compared to healthy controls. IL-17 and occludin levels were comparable between the three groups. Serum HMGB1 levels in EM patients were higher compared to the control group. Mig-SCog and HIT-6 scores were higher in the CM + MOH group compared to EM patients. HADS-A and HADS-D scores were significantly higher in the CM + MOH group compared to EM patients and healthy controls, and they were also higher in EM patients compared to healthy subjects. LPS levels were correlated with VE-cadherin and occludin levels. The number of monthly migraine headache days was positively correlated with serum LPS, HIF-1α, VE-cadherin, and IL-6 levels, HADS-A, HADS-D, HIT-6, and MigSCog scores. Conclusion: We have evidence for the first time that CM + MOH is associated with elevated serum LPS and LBP levels suggestive of LPS leak into the systemic circulation. Higher levels of nociceptive and/or pro-inflammatory molecules such as HMGB1, HIF-1α, IL-6, and CGRP may play a role in trigeminal sensitization and neurobiology of MOH. Intestinal hyperpermeability and consequent inflammatory response should be considered as a potential contributory factor in patients with MOH. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: We primarily aimed to ascertain whether treatment with OnabotulinumtoxinA (BoNTA) might influence the extent of the interictal burden and cutaneous allodynia in patients with chronic migraine (CM). Methods: Seventy CM patients, who received three consecutive cycles of BoNTA, were studied. The interictal burden was assessed with the Migraine Interictal Burden Scale (MIBS-4), while cutaneous allodynia was examined with the Allodynia Symptom Checklist (ASC-12) together with PI-NRS VAS to obtain hair brushing scores, and then these were compared from baseline (T0) to the last efficacy evaluation follow-up (T1). Efficacy outcomes, mostly mean headache days (MHD) and "Headache Impact Test" scores, were also assessed between T0 and T1. Results: BONTA improved the interictal burden, with a decrease in MIBS-4 scoring by an average of −7 at T1, compared to baseline (p < 0.001). The percentage of patients with a moderate/severe interictal burden was substantially decreased. Likewise, BoNTA reduced the extent of cutaneous allodynia, with a significant reduction in both the ASC-12 (1 vs. 6; p < 0.001) and PI-NRS VAS (1 vs. 5; p < 0.001) to hair brushing median scores at T1, compared to baseline. Reduced MHD rates were significantly associated with a smaller interictal burden at T1. The efficacy of BoNTA, with a significant reduction in MHD and HIT-6 scores at T1 compared to T0, was re-confirmed. Conclusions: BoNTA resulted in a statistically significant reduction in the interictal burden and also improved cutaneous allodynia. The reduction in ictal burden was associated with the down-scaling of the interictal burden. Hence, BoNTA improved the full spectrum of migraine impairment by diminishing the clinical expression of central sensitization. [ABSTRACT FROM AUTHOR]

Objective: To evaluate self‐reported substance user profiles for individuals with migraine and compare these to the general population. Background: There is increasing attention to lifestyle influences such as substance use as presumed migraine triggers. Methods: Data on substance use were collected by survey in a large migraine cohort and from the biannual survey in the general Dutch population for substances. A representative cohort of Dutch patients with migraine (n = 5176) and the Dutch general population (n = 8370) was included. Patients with migraine were subdivided into episodic (EM) and chronic migraine (CM). Substance consumption was compared between the general population and patients with migraine, and between migraine subgroups after standardization for sex and level of education. Results: Included patients with migraine were 83.4% female (4319/5176) and had a mean (standard deviation) age of 44.8 (11.3) years. Patients with migraine reported less illicit drug use (odds ratio [OR] 0.48, 95% confidence interval [CI] 0.42–0.55; p < 0.001), less current and lifetime smoking (OR 0.60, 95% CI 0.55–0.65; p < 0.001 and OR 0.75, 95% CI 0.71–0.79; p < 0.001), and less current alcohol consumption (OR 0.66, 95% CI 0.62–0.70; p < 0.001) compared with the general population. Prevalence of substance use was compared between CM and EM participants and showed higher illicit drug use (OR 1.73, 95% CI 1.11–2.69; p = 0.011), higher current smoking (OR 1.61, 95% CI 1.22–2.11; p < 0.001) but less alcohol use (OR 0.54, 95% CI 0.43–0.68; p < 0.001) for participants with CM compared with EM. No differences were found for a history of smoking (OR 1.18, 95% CI 0.92–1.50, p = 0.19). Conclusions: Individuals with migraine are less likely to use illicit drugs, smoke, or drink alcohol compared with the general population. Patients with CM less often consume alcohol, while they more often use illicit drugs and smoke compared to those with EM. [ABSTRACT FROM AUTHOR]

Objective: To determine the effect of the introduction of the calcitonin gene–related peptide monoclonal antibodies (CGRP mAbs) in 2018 on the prescribing of older medications for the prevention of chronic migraine. Background: Prior to 2018, the preventive treatment of migraine borrowed from medications intended to treat other illnesses with the last medication, onabotulinumtoxinA, receiving Food and Drug Administration (FDA) approval for the prevention of chronic migraine in 2010. The FDA approval of three CGRP mAbs in 2018 provided the ideal natural experiment to assess how the introduction of these medications, and a fourth in 2020, affected the generally stable migraine preventive medications market. Methods: We performed a retrospective cohort analysis using the aggregated de‐identified data of 6595 patients. The percentage of patients with chronic migraine who had been prescribed one of ten most prescribed oral preventive medications or onabotulinumtoxinA, or any of the four CGRP mAbs, were calculated relative to the total number of patients with chronic migraine who received a prescription for any medication from our clinic during the pre‐CGRP mAb years of 2015–2017 and post‐approval years of 2019–2021. Results: We observed a statistically significant decrease in the prescription of the top 10 most prescribed medications after the introduction of the CGRP mAbs overall (1456/3144, 46.3%, to 1995/4629, 43.1%, p = 0.001), as well as with most individual medications, including large decreases in verapamil (230/3144, 7.3%, to 125/4629, 2.7%; p < 0.001), the tricyclic antidepressants (494/3144, 15.7%, to 532/4629, 11.5%; p < 0.001), topiramate (566/3144, 18.0%, to 653/4629, 14.1%; p < 0.001), and onabotulinumtoxinA (861/3144, 27.4%, to 1134/4629, 24.5%; p = 0.001). Conclusion: The introduction of the CGRP mAbs during 2018 resulted in a decrease in utilization of most oral medications and onabotulinumtoxinA for the prevention of migraine. Future work should continue to observe how the prescription patterns of these medications evolve with time. [ABSTRACT FROM AUTHOR]

Background: Treatment with OnabotulinumtoxinA (BoNT-A) is effective as a preventive treatment for chronic migraine (CM). Preclinical studies suggest that the mechanism of action of BoNT-A in migraine is based on blocking unmyelinated C fibers. We aimed to investigate whether the muscle-relaxing effect of BoNT-A is associated with the preventive mechanism in patients with chronic migraine by measuring the stiffness, pain thresholds, and tenderness of the BoNT-A-applied muscles. Methods: A total of 22 patients with CM who were already in BoNT-A treatment participated in this longitudinal prospective study. Pericranial muscle stiffness was measured using ultrasound shear wave elastography, which measures the speed of shear waves propagating through the muscle. Pressure pain thresholds (PPT) were obtained via algometry, and muscle tenderness was measured via manual palpation. Measurements were made before BoNT-A injections and six weeks after the treatment. The measurements were performed while the muscles were maximally relaxed. The patients also completed daily diaries on headache and neck pain. Results: No change was observed in muscle stiffness (p = 0.737) or pericranial muscle tenderness (p = 0.400). The PPT over the trapezius muscles increased from 250 kPa before treatment to 304 kPa six weeks after treatment (p = 0.027). No change was observed on the temporalis muscles (p = 0.200) nor the non-dominant index finger (p = 0.067). BoNT-A decreased neck pain (p = 0.008) and headache (p = 0.007). Conclusions: The findings suggest that BoNT-A leads to the desensitization of cutaneous and muscle nociceptors in the head and neck regions, whereas muscle relaxation might not be an important part of the anti-migraine effect. [ABSTRACT FROM AUTHOR]

In chronic migraine with medication overuse (CM-MOH), sensitization of visual cortices is reflected by (i) increased amplitude of stimulus-evoked responses and (ii) habituation deficit during repetitive stimulation. Both abnormalities might be mitigated by inhibitory transcranial neurostimulation. Here, we tested an inhibitory quadripulse repetitive transcranial magnetic stimulation (rTMS-QPI) protocol to decrease durably visual cortex excitability in healthy subjects (HS) and explored its therapeutic potential in CM-MOH patients. Pattern-reversal visual evoked potentials (VEP) were used as biomarkers of effect and recorded before (T1), immediately after (T2), and 3 h after stimulation (T3). In HS, rTMS-QPI durably decreased the VEP 1st block amplitude (p < 0.05) and its habituation (p < 0.05). These changes were more pronounced for the P1N2 component that was modified already at T2 up to T3, while for N1P1 they were significant only at T3. An excitatory stimulation protocol (rTMS-QPE) tended to have an opposite effect, restricted to P1N2. In 12 CM-MOH patients, during a four-week treatment (2 sessions/week), rTMS-QPI significantly reduced monthly headache days (p < 0.01). In patients reversing from CM-MOH to episodic migraine (n = 6), VEP habituation significantly improved after treatment (p = 0.005). rTMS-QPI durably decreases visual cortex responsivity in healthy subjects. In a proof-of-concept study of CM-MOH patients, rTMS-QPI also has beneficial clinical and electrophysiological effects, but sham-controlled trials are needed. [ABSTRACT FROM AUTHOR]

Background: Neuroinflammation, mediated by the activation of microglia, contributes to central sensitization, which is associated with the development of chronic migraine (CM). TREM1 receptors amplify the inflammatory response. However, their relationship to CM is unclear. Thus, this study endeavoured to elucidate the exact role of TREM1 in CM. Methods: Nitroglycerin (NTG) was repeatedly administered intraperitoneally to establish the CM model. Mechanical and thermal sensitivities were assessed using von Frey filaments and hot plate assays. Using Western blotting, TREM1, NF-κB pathway, NLRP3 inflammasome components, and proinflammatory cytokines were all detected. Immunofluorescence was used to examine the cellular distribution of TREM1 and NLRP3, the number of microglia, immunoreactivity, and morphological changes. We examined the effects of TREM1 antagonists (LR12) and NF-κB inhibitors (PDTC) on pain behaviour, as well as the production of c-fos and CGRP. Additionally, we investigated whether LR12 and PDTC affect the activation of microglia and the NLRP3 inflammasome. We synthesized siRNA and TREM1-overexpressing plasmids to transfect BV2 cells treated with LPS and normal BV2 cells and treated TREM1-overexpressing BV2 cells with PDTC. The NF-κB pathway, NLRP3 inflammasome components, and proinflammatory cytokines were quantified using Western blotting. Results: Following NTG administration, the expression of TREM1 was significantly upregulated and exclusively localized in microglia in the TNC, and was well co-localized with NLRP3. Furthermore, activation of the classical NF-κB pathway was observed. Pre-treatment with LR12 and PDTC effectively attenuated mechanical hypersensitivity, suppressed the expression of c-fos and CGRP, and inhibited NF-κB activity in CM mice. Additionally, inhibition of TREM1 and NF-κB activity mitigated NTG-induced microglia and NLRP3 activation, as well as proinflammatory cytokines production. In vitro, knockdown of TREM1 resulted in attenuated activation of the NF-κB pathway following lipopolysaccharide (LPS) treatment and reduced expression of NLRP3 inflammasome components as well as proinflammatory cytokines. After TREM1 overexpression, the NF-κB pathway was activated, NLRP3 inflammasome components and proinflammatory cytokines were upregulated, and PDTC reversed this phenomenon. Conclusions: Our findings suggest that TREM1 regulates microglia and NLRP3 activation via the NF-κB pathway, thereby contributing to central sensitization and implicating its involvement in chronic migraine pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Migraine is a common cause of disability and loss of work. Migraine attacks are a complex brain event that unfolds over hours to days, in a recurrentmanner.A high frequency of migraine attacks can lead to frequent intake of acute medication, which may result in medication-overuse headache. Therefore, prophylaxis of migraine is justified as an important goal. Objective: To study and compare the clinical effectiveness and side effects of various migraine prophylactic drugs. Materials and methods: The patients fulfilling the inclusion and exclusion criteria were enrolled into this randomized, single blind study carried out in the patients visiting the Neurology OPD of Gauhati Medical College and Hospital, Guwahati from November 2022 to October 2023and were prescribed one of the following migraine prophylactic drugs-propranolol, amitriptyline, divalproex and desvenlafaxine. The initial four weeks were used for drug dose titration to minimum effective or maximum tolerable dosage and after optimal dose titration, the following 12 weeks were used to assess the efficacy of the drugs. MIDAS(Migraine Disability Assessment Score) questionnaire and Headache Impact Test-6(HIT-6) along with drug diary were used to assess the pre and post drug intervention quality of life which will help in assessing the efficacy of the drugs being used. Results: The study had a total of 100 patients with a median age of 28 years, with most of the patients presenting in the third decade of life. The male to female ratio was 1:2.3. The mean MIDAS scores at day 0 and at 3 months for the propranolol group were 18.9 and 7.20; for amitriptyline group it was 16.43 and 8.21, for divalproex it was 16.28 and 9.77, and for desvenlafaxine it was 17.5 and 8.5 respectively. The mean HIT-6 scores at day 0 and at 3 months for the propranolol group were 54.52 and 41.60; for theamitriptyline group it was 52.85 and 45.33, for divalproex it was 53.2 and 44.71, and for desvenlafaxine it was 52.18 and 42.26 respectively. All the 4 groups had comparable reduction in headache burden and number of headache days permonth based on mean MIDAS and HIT-6 scores. Conclusion: All the 4 groups had comparable reduction in headache burden and number of headache days per month based on mean MIDAS and HIT-6 scores and on t-test there was no significant difference in the mean scores between the groups indicating similar efficacy of the drugs used in the study. There were no adverse or side effects noted in any of the patients. [ABSTRACT FROM AUTHOR]

Background/aim: In this study, it was aimed to retrospectively compare the effect of greater occipital nerve (GON) block performed with ultrasonography using low (0.3%) and high (0.5%) concentrations of bupivacaine on pain scores and patient satisfaction in chronic migraine (CM). Materials and methods: The mean number of days with pain, the mean duration of pain in the attacks, and the highest numerical rating scale (NRS) scores recorded in the 1 month preblock and 1 and 3 months postblock of 80 patients (40 for Group 1, 0.3% bupivacaine; 40 for Group 2, 0.5% bupivacaine) who underwent ultrasonography-guided GON block were recorded from the patient file data. According to the protocol applied by our clinic, GON block was applied to each patient 6 times with the same procedures, in total. Results: While there was a statistically significant difference between the groups in terms of the number of days with pain and the maximum NRS score in the 1-month preblock evaluation (p = 0.01, p < 0.001), at 3 months postblock, no statistical difference was observed in terms of the number of days with pain, duration of pain, or NRS score (p = 0.961, p = 0.108, and p = 0.567). In the intragroup evaluations, at 3 months postblock, the number of days with pain decreased from 17.5 days to 7 days in Group 1 and from 24.0 days to 8.0 days in Group 2. The duration of pain and maximum NRS values were statistically significantly decreased in the intragroup evaluation in both groups pre and postblock. Conclusion: Complications arising from the procedure and the local anesthetic used are essential points to consider in applying GON block. In CM treatment using GON block application, a similar effect to the standard local anesthetic application (0.5%) can be achieved by administering local anesthetic at a lower dose (0.3%). [ABSTRACT FROM AUTHOR]

Background: Dry eye disease (DED) and migraine, two common disorders with public health concerns, may have a bidirectional relationship. Population-based studies have found that migraine patients have higher odds of DED and vice versa. We aimed to evaluate and compare the presence of DED symptoms and objective signs between migraine patients and non-migraine controls. Methods: This was a case-control study. We prospectively enrolled 60 consecutive migraine patients (30 episodic and 30 chronic) presenting in the medicine outpatient department, aged 18–65 years, and 60 non-migraine healthy controls visiting the ophthalmology department for refractive errors between February 2019 and June 2021. Consecutive migraine patients and non-migraine healthy controls were assessed in the ophthalmology department at Hindu Rao Hospital, Delhi by the Ocular Disease Surface Index (OSDI) questionnaire for DED symptoms and objectively by measuring tear break-up time (TBUT), Schirmer test (ST), and Fluorescein staining (FS). DED severity was assessed by the Odessey algorithm. Results: The mean OSDI score was significantly greater in migraineurs than in controls (31.2 ± 19.8 vs 22.7 ± 15.6; p = 0.010). 45% of migraineurs had DED compared to 18.3% in controls (p = 0.002), whereas 23.3% had severe DED compared to one (1.7%) in the control group (p < 0.001). Migraineurs, compared to controls, had significantly lower mean TBUT (10.1 ± 6.5 s versus 13.4 ± 5.8 s; p = 0.004), higher FS grade (1.57 ± 1.4 versus 0.92 ± 1.2; p = 0.008) and lower ST scores (11.5 ± 5.8 mm versus 14.2 ± 6.2 mm; p = 0.014). Migraineurs with DED, compared with those without DED, had longer migraine disease duration, higher frequency, pain severity, and disability. Compared to episodic migraine, chronic migraine patients had significantly lower TBUT (11.9 ± 5.9 vs 8.3 ± 6.7; p = 0.30) and higher OSDI scores (25.7 ± 20.1 vs 36.8 ± 18.2). Conclusions: This study showed that migraine patients had an increased presence of DED and severe DED compared to controls. Further, increased migraine severity and chronicity were associated with increased subjective symptoms and objective signs of DED. Migraine patients with DED were more disabled.CM patients had more DED symptoms and signs. [ABSTRACT FROM AUTHOR]

Since the high burden of chronic migraine (CM), it is challenging to identify the best prevention treatment. Based on the preclinical evidence about the different therapeutic targets of onabotulinumtoxinA (BT-A), acting on C-fibers, and anti-CGRP monoclonal antibodies (mAbs), acting on Aδ-fibers, the rationale of using alternative or combining therapies has been hypothesized. Until now, the association of BT-A and mAbs has been poorly investigated. This study evaluated whether mAbs are effective and safe in CM patients previously treated with BT-A, either as an alternative or add-on treatment. We enrolled 47 patients: according to the response to BT-A treatment, patients were defined as non-responder (NR) and partial-responder (PR). NR were shifted to mAbs. PR were randomly divided into those who added mAbs therapy (PR-P) and those who shifted treatment (PR-S), interrupting BT-A. Clinical variables were collected at baseline, after three and six months. Study results evidenced the efficacy of mAbs in improving clinical outcomes in CM patients, with a better response in the PR group. No statistically significant differences in clinical changes were observed between PR-P and PR-S groups. No safety concerns were raised in combined treatments. Preventive prophylaxis with mAbs is effective, even in difficult to treat CM patients. Further studies, with larger samples, are needed to highlight a potential additive effect of combined therapies. [ABSTRACT FROM AUTHOR]

The aim of present study is to assess postural alterations and musculoskeletal dysfunctions over all spine in patients with chronic migraine and chronic tension type headache, moreover to highlight the differences between these two forms of primary headache. A Cross sectional study was adopted to evaluate the musculoskeletal profile in patients with chronic migraine and with chronic tension type headache. The Bio photogrammetric evaluation was performed using the postural assessment software PAS/SAPO, while unilateral passive accessory intervertebral motion (PAIM s) were applied for manual examinations of spine segments from C0 to L5 vertebra. The One-way Analysis of Variance (ANOVA) test was used to compare the three groups with the software GraphPad InStat 3.06. A total of 60 patients were recruited, 20 for chronic tension type group, 20 for chronic migraine group and 20 healthy controls. The most interesting findings was that patients with chronic primary headaches presented postural alterations in all parameters (cranio-vertebral angle and lumbar-pelvic angle) and musculoskeletal dysfunctions in all spine with respect to healthy controls. Finally, the most clinically relevant finding was that no differences were found between chronic migraine and chronic tension type headache concerning the postural alterations nor the musculoskeletal dysfunctions. The sensitization acts as a substrate or consequence of these musculoskeletal dysfunctions in chronic primary headache. Therefore, non-pharmacological treatments targeted in the musculoskeletal system may be a good option in the management of chronic primary headache, especially when these therapies integrate various techniques that involve all spine. • Primary headaches presented musculoskeletal disorders throughout the spine. • ●No differences were found in postural alteration between the two primary headaches. • ●No differences were found in musculoskeletal disorders between the two primary headaches. [ABSTRACT FROM AUTHOR]

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Abstract Introduction Erenumab, a fully human monoclonal antibody against the calcitonin gene-related peptide receptor, is approved in Japan for the prevention of adult migraine. This post-hoc analysis evaluated the efficacy of erenumab in Japanese patients with low-frequency episodic migraine (LFEM) versus those with high-frequency episodic migraine (HFEM) and chronic migraine (CM). Methods A pooled analysis of data from the 24-week double-blind treatment phases (DBTPs) of phase 2 and 3 studies evaluated the efficacy of once-monthly erenumab 70 mg in Japanese patients. Patients were categorized into subgroups by monthly migraine days (MMD): LFEM and HFEM/CM. The main efficacy outcomes were change from baseline in MMD, acute migraine-specific medication treatment days (MSMD), and six-item Headache Impact Test (HIT-6™) scores. Results Patients with migraine (n = 532) were included in the analysis (LFEM, n = 215; HFEM, n = 215; CM, n = 102). Overall, mean age was 44 years, 86.5% were female, and 63.3–88.2% had used or were taking migraine preventive treatment at baseline. Throughout the DBTP, the placebo-adjusted mean change from baseline in MMD, MSMD, and HIT-6 scores with erenumab was similar across LFEM and HFEM/CM subgroups. The proportion of patients achieving at least 50% or 75% reduction from baseline in MMD and MSMD was similar across migraine frequency groups. Reduction in MMD moderately correlated with improvement in HIT-6 scores in the LFEM and HFEM/CM groups. Furthermore, the proportion of patients converting from HFEM/CM to LFEM during the DBTP was higher in the erenumab group than in the placebo. Conclusion In Japanese patients with different migraine frequencies, erenumab treatment resulted in significant improvements in MMD, MSMD, and headache impact. This pooled analysis of data from phase 2 and 3 studies increases confidence that erenumab is efficacious in patients with high MMD, which is associated with increased disability.

Abstract Introduction Chronic migraine (CM) patients commonly take acute headache medications, often resulting in medication overuse (MO). This post hoc analysis evaluated the efficacy of fremanezumab in CM patients from Japan with and without MO, which is not yet established. Methods A multicenter, double-blind, parallel-group, phase 2b/3 trial randomized patients (1:1:1) to monthly fremanezumab via subcutaneous injection (initial dose: 675 mg, second/third doses: 225 mg), quarterly fremanezumab (initial dose: 675 mg, second/third doses: placebo), or placebo for 3 months. This post hoc analysis analyzed data from Japanese patients with and without MO (monthly use of acute headache medication ≥ 15 days, migraine-specific acute medication ≥ 10 days, or combination medication ≥ 10 days). Outcomes included the original primary endpoint of average headache days of moderate or greater severity per month (HDs), the proportion of patients with ≥ 50% reduction in HDs and the proportion of patients changing status from with to without MO. Results Of 479 patients enrolled, 320 (66.8%) had baseline MO. Monthly average HDs were significantly reduced versus placebo with fremanezumab in both patients with MO (mean [standard error] difference vs. placebo: monthly – 2.0 [0.6], p = 0.0012; quarterly – 1.8 [0.6], p = 0.0042) and without MO (– 1.6 [0.8], p = 0.0437; – 1.5 [0.8], p = 0.0441). Significantly more fremanezumab-treated patients with MO (monthly 28/108 [25.9%], p = 0.0040 quarterly 25/99 [25.3%], p = 0.0070) or without MO (18/50 [36.0%], p = 0.0132; and 21/60 [35.0%], p = 0.0126) had ≥ 50% reduction in HDs versus placebo (12/111 [10.8%] and 7/49 [14.3%], respectively). A significantly greater proportion of fremanezumab-treated patients reverted to no MO (monthly 50/108 [46.3%], p = 0.0115; quarterly 44/99 [44.4%], p = 0.0272) vs. placebo (33/111 [29.7%]). Conclusion Fremanezumab appears effective as preventive migraine treatment in Japanese CM patients with or without MO while also being beneficial in reducing MO.

Abstract Background Chronic migraine (CM) is a significant neurological condition affecting a substantial portion of the global population. The economic burden of CM includes both direct healthcare costs and indirect costs resulting from productivity losses and intangible impacts on patients’ quality of life. However, there is limited research that comprehensively evaluates all cost components associated with CM, highlighting the need for a systematic review. Methods We conducted a systematic literature search in databases including MEDLINE, Embase, and CINAHL to identify studies estimating the cost of illness of chronic migraines. The search was restricted to English language articles published from inception to October 2021, and only findings from Organisation for Economic Co-operation and Development (OECD) countries were included. Methodology features and key findings were extracted from the studies, and reported costs were converted to GBP for cross-country comparisons. Results Thirteen cost-of-illness studies on CM from various OECD countries were included in this review. The studies demonstrated substantial variations in monetary estimates, but consistently highlighted the considerable economic burden of CM. Direct costs, particularly hospitalisation and medication expenses, were identified as the highest contributors. However, indirect costs, such as productivity losses due to absenteeism and presenteeism, were often underexplored in the reviewed studies. Additionally, intangible costs related to emotional and social impacts on patients were largely overlooked. Conclusion Chronic migraine imposes a significant economic burden on individuals, healthcare systems, and society. Policymakers and healthcare stakeholders should consider both direct and indirect cost components, as well as intangible costs, in developing targeted strategies for effective CM management and resource allocation. Further research focusing on comprehensive cost assessments and sensitivity analyses is needed to enhance the understanding of CM’s economic implications and inform evidence-based healthcare policy decisions. Addressing these research gaps can alleviate the economic burden of CM and improve patient outcomes.

Abstract Background Migraine, a complex brain disorder, is regarded as a possible clinical manifestation of brain energy dysfunction. The trigeminovascular system is considered the basis for the pathogenesis of migraine, hence we depicted the proteomics profiling of key regions in this system, then focusing on protein alterations related to mitochondrial function. The aim of this study is to illustrate the role of mitochondria in migraine. Methods A mouse model of chronic migraine (CM) was established by repeated nitroglycerin (NTG) stimulation and evaluated by von-Frey filaments, a hot plate and a light-dark box. Differentially expressed proteins (DEPs) in some subcortical brain regions of the trigeminovascular system were screened through liquid chromatography-tandem mass spectrometry (LC‒MS/MS) to analyse the specificity of key signaling pathways in different brain regions. And then mitochondrial function, structure and dynamics were determined by qPCR, ELISA, and transmission electron microscope (TEM). Finally, the effect of mitochondrial intervention-Urolithin A (UA) on CM was investigated. Results Repeated NTG injection triggered photophobia, periorbital and hind paw allodynia in mice. The proteomics profiling of CM model showed that 529, 109, 163, 152 and 419 DEPs were identified in the thalamus, hypothalamus, periaqueductal grey (PAG), trigeminal ganglion (TG) and trigeminocervical complex (TCC), respectively. The most significant changes in the brain region-specific pathways pointed to thalamic mitochondrial impairment. NTG induced mitochondrial structural disruption, dysfunction and homeostatic dysregulation, which could be partially attenuated by UA intervention. Conclusion Our findings highlight the involvement of mitochondrial damage in the thalamus in central sensitization of CM, which provides evidence of possible metabolic mechanisms in migraine pathophysiology.