Search Results (61)

The neuropeptide calcitonin gene-related peptide (CGRP), especially α-CGRP, is central in migraine pathophysiology. Although CGRP is a therapeutic target and potential biomarker, inconsistencies in measurement procedures need to be further studied for reliable results. This study aims to analyze factors influencing plasma CGRP measurement. Chronic migraine (CM) patients were recruited in our Headache Unit. Blood samples were collected before and during treatment with CGRP monoclonal antibodies, processed and stored. Levels of CGRP were measured with isoform-specific enzyme-linked immunosorbent assay (ELISA) tests. Statistical tests were used to assess concentration changes and group differences. The addition of protease inhibitors (PIs) to plasma samples significantly increased α-CGRP level detection, with a smaller effect on β-CGRP. No correlation was found between the α- and β-CGRP levels in plasma. The plasma-PI samples showed higher CGRP concentrations than in serum. The α-CGRP levels decreased during treatment while the β-CGRP levels remained stable. α-CGRP and age correlated negatively, but no sex-related differences were observed either for α- or β-CGRP. PI improved CGRP detection in plasma. The α-CGRP levels, which were influenced by age, decreased with specific treatment, suggesting its potential role as a biomarker. In contrast, β-CGRP remained stable, suggesting independent regulation of both isoforms. Full article

Migraine is a neurovascular paroxysmal disorder characterized by neurogenic inflammation and has a remarkable impact on the quality of life. The Food and Drug Administration (FDA) approved onabotulinumtoxin A in 2010 for the prophylactic treatment of chronic migraine. Today, in its 4th decade, it is approved in 100 countries for 15 main indications. Its mechanism of action, based on the inhibition of neurotransmitter release from primary sensory neurons, is very complex: it affords antinociception, but it also has an analgesic effect on neuropathic pain conditions and reduces the need for rescue medications. Genetic variants have been investigated for their potential role in the pathogenesis and clinical expression of migraine and of the response to treatments. These studies primarily involved genes associated with vascular regulation and cardiovascular pathology, including those encoding angiotensin-converting enzyme (ACE) and methylenetetrahydrofolate reductase (MTHFR). However, epigenetics and, particularly, genetic and epigenetic modifications are still poorly studied in terms of understanding the mechanisms implicated in susceptibility to migraine, aura, chronification and response to symptomatic and preventive treatments. In particular, the aim of the present study is to gather evidence on the genetic variants and epigenetic modifications affecting the pathway of the calcitonin gene-related peptide (CGRP), the target of onabotulinumtoxin A and of all the novel monoclonal antibodies. Full article

Headache disorders are among the most prevalent and disabling neurological conditions worldwide, affecting more than three billion individuals and contributing to a substantial socioeconomic burden. Despite the availability of pharmacologic treatments such as triptans, NSAIDs, and CGRP monoclonal antibodies, a significant proportion of patients remain refractory or intolerant to these therapies. The sphenopalatine ganglion (SPG), a parasympathetic neural structure in the pterygopalatine fossa, is increasingly recognized as a critical node in the pathophysiology of primary headache disorders. SPG blocks—using local anesthetics, neurolytic agents, or electrical neuromodulation—offer a minimally invasive therapeutic approach by disrupting nociceptive transmission and autonomic activation. This narrative review synthesizes the anatomical and physiological rationale for SPG intervention, details various procedural techniques, evaluates clinical evidence across headache subtypes, and explores future research directions. Conditions covered include migraine, cluster headache, tension-type headache, trigeminal neuralgia, and persistent idiopathic facial pain. With expanding evidence and evolving technologies, SPG-targeted interventions have the potential to reshape the management of refractory headaches and facial pain syndromes. Full article

Background/Objectives: Migraines contain neurological and gastrointestinal manifestations. The first specific migraine preventive drugs, CGRP monoclonal antibodies (mAbs), though efficacious and very well-tolerated in general, induce constipation as their main adverse event. Our goal was to analyze the role of the two isoforms of CGRP in the development of constipation in patients treated with mABs. Methods: We prospectively measured by ELISA circulating alpha- and beta-CGRP levels in 133 high-frequency episodic/chronic migraine patients before and three months after mAbs treatment and correlated these levels with a number of clinical variables, including the development of constipation during this treatment. Results: Twelve patients (9.0%) noticed de novo constipation with mAbs. Demographics, efficacy end-points, profile of preventive treatment, and comorbidities, with the exception of anxiety/depression, were superimposable between patients with or without emergent constipation. Basal alpha-CGRP levels (49.5 [29.2–73.8] pg/mL) significantly decreased at month three of treatment (40.5 [20.4–61.0] pg/mL; p < 0.0001), both in patients with and without emergent constipation. Pre-treatment circulating beta-CGRP levels (4.0 [2.1–6.2] pg/mL) remained unchanged after three months of treatment (4.3 [2.5–6.0] pg/mL; p = 0.574) in the whole series but were selectively reduced in patients with emergent constipation (p = 0.034). Conclusions: This is the first work exploring the role of the two isoforms of CGRP in the pathophysiology of constipation with mAbs. Our results suggest that the antagonism on the alpha-CGRP isoform plays a relevant role in the antimigraine action of mABs but not in the development of constipation. By contrast, the specific reduction in beta-CGRP levels in patients with emergent constipation supports the role of beta-CGRP antagonism in the development of this adverse event. Full article

Background: Migraine is associated with structural brain abnormalities, including cortical thickness changes. Anti-calcitonin gene-related peptide monoclonal antibodies (anti-CGRP mAbs) are a novel therapy for migraine prevention, but their effects on cortical structures are poorly understood. Methods: In this prospective age- and sex-matched controlled study, 30 migraine patients receiving either anti-CGRP mAbs (fremanezumab) (n = 15) or oral preventive medications (n = 15) underwent 3T MRI scans before and after treatment. Treatment response was defined as a ≥50% reduction in monthly headache days after 3 months. Cortical thickness was analyzed across 46 cortical regions, comparing patients treated with anti-CGRP mAbs to those receiving oral preventive treatment, as well as responders to non-responders within the anti-CGRP group. Results: Cortical thickness changes did not differ significantly between the anti-CGRP and oral treatment groups. However, among patients receiving anti-CGRP mAbs, responders showed significant decreases in cortical thickness compared to non-responders, particularly in the right caudal anterior cingulate (p = 0.026) and left rostral middle frontal cortex (p = 0.007). These cortical changes correlated with treatment response to anti-CGRP mAbs (β = −0.429, 95% CI [−0.777, −0.081], p = 0.016 in the right caudal anterior cingulate; β = −0.224, 95% CI [−0.390, −0.057], p = 0.008 in the left rostral middle frontal cortex). Conclusions: This exploratory study, based on a small sample size, suggests that cortical thickness changes may be associated with treatment response to anti-CGRP mAbs rather than with CGRP mAb treatment itself. Further studies with larger cohorts are needed to confirm these findings. Full article

Background/Objectives: Pediatric chronic migraine (CM) is a debilitating condition with challenging management due to diagnostic complexities and a lack of evidence-based treatment. Calcitonin gene-related peptide (CGRP)-targeted therapies have transformed adult CM management, but their use in pediatric populations is underexplored. This study evaluated the safety and efficacy of CGRP-targeted therapies combined with structured lifestyle modifications in Korean pediatric patients with CM. Methods: This retrospective study examined 10 pediatric CM patients treated at Gangnam Severance Hospital from 2021 to 2024. Inclusion criteria were as follows: (1) Pediatric Migraine Disability Assessment Scale (PedMIDAS) score ≥ 30, (2) >2 failed preventive therapies, and (3) ≥8 migraine days per month. Patients received CGRP monoclonal antibodies or antagonists, alongside sleep, dietary, and exercise interventions. Changes in migraine burden, neuropsychological outcomes, and adherence to lifestyle interventions were assessed over 12 months. Results: Migraine frequency significantly decreased from a median of 26.5 to 14 days per month (p < 0.001); PedMIDAS scores declined from 58.5 to 48.0 (p = 0.037); and acute analgesic use was reduced from 14 to 5 days per month (p < 0.001). Adherence to lifestyle interventions improved significantly (p < 0.001). No serious adverse events were reported, and minor side effects, such as injection site pain and dizziness, were self-limiting. Conclusions: CGRP-targeted therapies, combined with structured lifestyle modifications, safely and effectively reduce migraine burden in pediatric CM patients. These therapies have facilitated sustainable improvements in management and support their integration into comprehensive pediatric CM care. This study highlights the importance of integrating pharmacologic and lifestyle-based approaches for holistic pediatric migraine management. Full article

Background: Anti-CGRP (receptor) antibodies are approved for the preventive treatment of migraines and are increasingly used due to their favorable safety profile and potent efficacy. However, as CGRP is one of the most potent vasodilators, concerns have been raised regarding the possible impact of these drugs on arterial blood pressure. Methods: We present a retrospective cohort study at a tertiary headache center including a total of 259 patients with episodic and chronic migraine who received anti-CGRP antibody treatment for migraine prevention. Blood pressure was measured in a hospital using a standardized setting at baseline and at least at two follow-up visits. Significant increase in blood pressure was defined as an increase in systolic blood pressure ≥ 20 mmHg and/or an increase in diastolic blood pressure ≥ 10 mmHg from the baseline value. Results: Mean age of our population was 39.9 years (±12.1), and 217 (83.8%) were female. Blood pressure measurements between T0 and T2, incorporating all CGRP-antibody groups, showed a significant reduction in systolic (−3.3 mmHg; p = 0.001) and diastolic blood pressure (−2.3 mmHg; p = 0.021), respectively. The repeated-measures generalized linear model analysis revealed no significant variations between the CGRP antibodies relative to blood pressure. The most robust factor predicting systolic hypertensive measurements in the course of anti-CGRP antibody treatment was pre-existing hypertension at baseline (sum of mean squares 7.4; p = 0.019). Conclusions: Our data indicate that treatment with anti-CGRP (receptor) antibodies does not significantly increase blood pressure. However, it seems to be important to monitor patients with pre-existing arterial hypertension. Full article

Background/Objectives: Lasmiditan is a newly developed drug for the acute treatment of migraine attacks, but factors associated with its efficacy remain unclear. This study aimed to confirm the efficacy of lasmiditan started at 50 mg under various dosing conditions and identify factors associated with its efficacy. Methods: There are four reasons for prescribing lasmiditan: as an add-on to triptan, if triptan is ineffective, if triptan produces side effects, and when triptan is contraindicated. Lasmiditan was administered at a dose of 50 mg. The efficacy of lasmiditan was defined as the disappearance of headache or a 50% or greater reduction in headache intensity within two hours after dosing. This study included 108 patients with migraines who took lasmiditan. Results: The results for efficacy and the side effects of lasmiditan were as follows: effective without side effects (22), effective with mild side effects (32), ineffective (14), and severe side effects (40). The efficacy rate of lasmiditan 50 mg was 50.0% (54/108). The following factors were found to be associated with lasmiditan’s efficacy: sex, migraine classification, calcium channel blockers, and anti-calcitonin gene-related peptide monoclonal antibody (CGRP-mAb) treatment. The overall incidence of side effects was 66.7%, and the dropout rate was 37.0%. Somnolence was more prevalent in the effective group, and other side effects were more prevalent in patients who dropped out due to the side effects of lasmiditan. Conclusions: Lasmiditan is likely to be effective in males with severe migraine classification and receiving CGRP-mAb treatment. If mild somnolence is a side effect, the drug can be continued and may be effective. Full article

Background: Fremanezumab was the third CGRP antibody available in our hospital. This examination of our experience with fremanezumab is focused on identifying the predictors of response. Methods: This was a prospective observational study in which we included high-frequency episodic/chronic migraine (HF/CM) patients who were prescribed fremanezumab during the year 2023. Our research involved collecting data on their demographic details, diagnoses made, treatments received, prophylactic measures taken in the past, and any comorbid conditions present. The number of headaches was documented for one quarter prior to and after the initiation of fremanezumab. Results: Eighty-nine patients received fremanezumab (86.5% female, 45.8 ± 12.5 years old, 70.1% naive). The headache days decreased from 21.1 ± 7.6 to 12.4 ± 11.2 days during the initial three months of the treatment, and a total of 55 patients (61.8%) exhibited a response rate of ≥50%. Six out of ten patients refractory to erenumab for at least 6 months responded to fremanezumab. Totals of 17 and 26 patients had been treated at least with galcanezumab or erenumab. The elements influencing non-response were as follows: prior failure to respond to both erenumab and galcanezumab (p < 0.0001), HF/CM length (11.9 ± 7.1 years in non-responders vs. 5.8 ± 4.8 in responders; p < 0.001), the presence of fibromyalgia (p < 0.001), anxiety–depression (p < 0.001), an almost daily headache baseline (>28 days/month) (p < 0.0001), and analgesic overuse (p < 0.0001). The response rate was unaffected by age and experience. After a multivariate logistic analysis, almost daily headaches (p < 0.001), a length of HF/CM > 6 years (p = 0.015), and anxiety–depression (p = 0.017) remained significant. Fremanezumab showed excellent tolerance. Conclusions: These real-life results confirm the efficacy of fremanezumab. The main factors associated with a lack of response were almost daily/daily headaches and a disease duration > 6 years. Half of the patients who failed to respond to erenumab improved on fremanezumab, making it sensible to switch to a treatment with a different mechanism of action, but trying a third anti-CGRP treatment in patients with no response to both a receptor-targeted and a ligand-targeted CGRP antibody hardly seems justifiable from our experience. Full article

Background: Calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) are a breakthrough migraine treatment, but long-term compliance under limited public insurance coverage has not been well known. This study explores one-year treatment patterns and outcomes of CGRP mAbs using real-world data. Methods: This multicenter retrospective study included migraine patients treated with CGRP monoclonal antibodies (CGRP mAbs) from July 2022 to June 2023. Treatment discontinuation was defined as a gap of over 60 days between injections. Among patients with 12 months of follow-up, adherence was measured using the Proportion of Days Covered (PDC), calculated as the ratio of days covered to the follow-up duration, with PDC ≥ 80% indicating good adherence. Efficacy was also assessed, defined as a ≥50% reduction in monthly headache days and acute medication use. Results: The study included 140 patients (mean age 44.6 ± 12.1 years; 82.9% female). Migraine without aura was predominant (93.6%), and 65.0% had chronic migraine. CGRP mAbs discontinuation occurred in 71.4% of patients, primarily due to headache improvement (22.9%) or lack of efficacy (15.0%). Among 81 patients with 12 months of follow-up, good adherence was observed in 40.7% of patients. Among these patients, 60.6% achieved a ≥50% reduction in monthly headache days, and 51.9% showed a ≥50% reduction in monthly acute medication use. Conclusions: More than two-thirds of patients discontinued the CGRP mAb within 1 year, so these findings emphasize the need for strategies to improve adherence and optimize follow-up plans to enhance patient support. Full article

Background/Objectives: Migraines are a common neurological disorder that significantly impact women, especially during their reproductive years. Hormonal, neurological, and lifestyle factors shape migraine patterns, with fluctuations during menstruation, pregnancy, perimenopause, and menopause influencing migraine prevalence and severity. This expert opinion explores current challenges, therapeutic strategies, and future directions for personalized care, addressing the limited inclusion of women in clinical research across different life stages. Methods: In order to focus on hormonal influences, pharmacological and non-pharmacological therapies, including CGRP monoclonal antibodies, neuromodulation, and lifestyle interventions, a comprehensive analysis of literature, in particular on clinical trials, real-world studies, and guidelines on migraine management was performed. Emerging digital tools and AI-based approaches were also evaluated to improve personalized care for women with migraine. Results: Hormonal therapies, including contraceptives and HRTs, present both risks and benefits, particularly for women with migraines with aura, highlighting the need for individualized approaches. Advances in CGRP-targeted therapies have shown effectiveness in preventing refractory migraines. Non-pharmacological treatments, such as neuromodulation, acupuncture, and lifestyle adjustments, further expand the treatment landscape. However, research gaps remain, particularly regarding hormonal influences on migraines during pregnancy and menopause. Conclusions: Future research should prioritize female-specific clinical trials to better understand the impact of hormonal changes on migraines. Tailored therapies combining pharmacological, non-pharmacological, and digital solutions are essential for improving care. A multidisciplinary approach integrating personalized medicine, technological advancements, and patient education is crucial to optimizing outcomes and enhancing quality of life for women with migraine. Full article

Migraine and stroke are neurological disorders with significant global prevalence and impact. Recent advances in migraine therapy have focused on the calcitonin gene-related peptide (CGRP) pathway. This review examines the shared pathomechanisms between migraine and stroke, with emphasis on the role of CGRP. We analyze the current literature on CGRP’s functions in cerebrovascular regulation, edema formation, neuroinflammation, and neuroprotection. CGRP acts as a potent vasodilator and plays a crucial role in trigeminovascular activation during migraine attacks. In stroke, CGRP has demonstrated neuroprotective effects by improving collateral circulation and reducing ischemia-reperfusion injury. Concerns have been raised about the potential impact of CGRP inhibitors on stroke risk and outcomes. Studies in animals suggest that CGRP receptor antagonists may worsen cerebral ischemia by impairing collateral flow. We discuss the implications of these findings for the use of CGRP-targeting therapies in migraine patients, especially those at increased risk of stroke. Additionally, we explore the complex interplay between CGRP, endothelial function, and platelet activity in both conditions. This review highlights the need for further research to elucidate the long-term cerebrovascular safety of CGRP pathway inhibitors and to identify potential subgroups of migraine patients who may be at higher risk of adverse cerebrovascular events with these novel therapies. Full article

Background: Anti-calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) are clinically effective in preventing the migraine attacks, photophobia, and migraine auras associated with headaches. However, no study has yet investigated the effectiveness of CGRP mAbs in preventing migraine aura without headache. Case report: A female patient of 49 years old presented with a long history (since age 10) of photosensitivity and typical migraine auras without a headache. The symptoms slightly responded to oral medication, lomerizine chloride, but did not completely resolve. Just one day after the administration of galcanezumab, her photo-hypersensitivity and migraine aura had completely resolved. Consequently, the administration of the oral migraine preventive medication was discontinued. Monthly galcanezumab at a dose of 120 mg was continuously given and she did not re-experience any auras or headaches. Conclusions: The use of CGRP mAbs can be considered as a potential treatment in preventing migraine aura without headache. Currently, CGRP mAb is indicated only for migraines with and without auras. Given our findings and the promising effects of this medication for this migraine subtype, a large clinical trial is required to better assess the effects and potential adverse events of CGRP mAb in patients with migraine aura without headache. Full article

Post-traumatic headache (PTH) is a common and debilitating consequence of traumatic brain injury (TBI), often resembling migraine and tension-type headaches. Despite its prevalence, the optimal treatment for PTH remains unclear, with current strategies largely extrapolated from other headache disorders. This review evaluates the use of onabotulinumtoxin A (ONA) and anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) in the treatment of PTH. A comprehensive literature search was conducted on PubMed, including studies published up to September 2024, focusing on the efficacy, safety, and mechanisms of onabotulinumtoxin A and anti-CGRP mAbs in PTH. Both clinical trials and observational studies were reviewed. ONA, widely recognized for its efficacy in chronic migraine, has shown limited benefits in PTH with only one trial involving abobotulinumtoxin A in a cohort of 40 subjects. A phase 2 trial with fremanezumab, an anti-CGRP monoclonal antibody, failed to demonstrate significant efficacy in PTH, raising questions about the utility of targeting CGRP in this condition. ONA may offer advantages over anti-CGRP mAbs, not only in terms of its broader mechanism of action but also in cost-effectiveness and higher patient adherence. Both ONA and anti-CGRP mAbs are potential options for the management of PTH, but the current evidence is insufficient to establish clear guidelines. The negative results from the fremanezumab trial suggest that CGRP inhibition may not be sufficient for treating PTH, whereas onabotulinumtoxin A’s ability to target multiple pain pathways may make it a more promising candidate. Full article

Background: The advent of monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway has transformed the management of migraine, offering newfound optimism for clinicians and individuals with episodic migraine (EM) and chronic migraine (CM). While randomized controlled trials (RCTs) have provided crucial insights into the effectiveness and safety profiles of these treatments, their translation into real-world clinical practice remains a challenge. Objective: This review aims to conduct a comprehensive assessment of real-world studies, offering valuable insights tailored for practical application in clinical settings. Methods: We conducted a comprehensive literature search in PubMed, SCOPUS, and MEDLINE for real-life studies on erenumab, fremanezumab, and galcanezumab. Abstracts underwent rigorous screening by two reviewers for relevance. Data extraction from selected articles was performed using a standardized form, with verification by a second reviewer. Data synthesis was narrative, following PRISMA guidelines. Results: Our search included 61 pertinent studies conducted between 2019 and 1 March 2024. Real-world study designs demonstrated notable variability in the selection and inclusion of migraine patients, influenced by factors such as attack frequency, data collection criteria, and primary/secondary objectives. Key findings commonly reported considerable improvements in efficacy outcomes (migraine frequency, analgesic use, pain severity, and disability), high responder rates, and optimal safety and tolerability profiles. Conclusions: Real-world evidence underscores the role of anti-CGRP mAbs as targeted therapies for both CM and EM patients. The overall results indicate that the effectiveness and tolerability of anti-CGRP mAbs in real-world applications may exceed those observed in RCTs, an extraordinary finding in clinical neurology. Full article