Migraine Research Articles

A multi-centre, tolerability study of a cannabidiol-enriched Cannabis Herbal Extract for chronic headaches in adolescents: The CAN-CHA protocol

Introduction Cannabis products have been used in the management of headaches in adults and may play a role in pediatric chronic pain. Canadian pediatricians report increasing use of cannabis for the management of chronic headaches, despite no well-controlled studies to inform its dosing, safety, and effectiveness. The aim of our clinical trial is to determine the dosing and safety of a Cannabidiol (CBD)-enriched Cannabis Herbal Extract (CHE) for the treatment of chronic headaches in adolescents. Methods and analysis Youth, parents, and an expert steering committee co-designed this tolerability study. Twenty adolescents (aged 14 to 17 years), with a chronic migraine diagnosis for more than 6 months that has not responded to other therapies will be enrolled into an open label, dose escalation study across three Canadian sites. Study participants will receive escalating doses of a CBD-enriched CHE (MPL-001 with a THC:CBD of 1:25), starting at 0.2–0.4 mg/kg of CBD per day and escalating monthly up to 0.8–1.0 mg/kg of CBD per day. The primary objective of this study is to determine the safety and tolerability of CBD-enriched CHE in adolescents with chronic migraine. Secondary objectives of this study will inform the development of subsequent randomized controlled trials and include investigating the relationship between the dose escalation and change in the frequency of headache, impact and intensity of pain, changes in sleep, mood, function, and quality of life. Exploratory outcomes include investigating steady-state trough plasma levels of bioactive cannabinoids and investigating how pharmacogenetic profiles affect cannabinoid metabolism among adolescents receiving CBD-enriched CHE. Discussion This protocol was co-designed with youth and describes a tolerability clinical trial of CBD-enriched CHE in adolescents with chronic headaches that have not responded to conventional therapies. This study is the first clinical trial on cannabis products in adolescents with chronic headaches and will inform the development of future comparative effectiveness clinical trials. Trial registration CAN-CHA trial is registered with ClinicalTrials.gov with a number of register NCT05337033.

Patients' Experiences During the Long Journey Before Initiating Migraine Prevention with a Calcitonin Gene-Related Peptide (CGRP) Monoclonal Antibody (mAb).

Migraine is under-diagnosed and under-treated. Many people with migraine do not seek medical care, and those who do may initially receive a different diagnosis and/or be dissatisfied with provided care on their journey before treatment with a CGRP-mAb (calcitonin-gene-related-peptide monoclonal antibody). This is a cross-sectional, self-reported, online survey of subjects in Lilly's Emgality® Patient Support Program in 2022. Questionnaires collected insights into subjects' prior experiences with migraine and interactions with healthcare professionals before receiving CGRP-mAbs. Of the 250 participants with episodic and 250 with chronic migraine, 90% were female and white with a mean age of 26.2years (±11.9) at diagnosis and 40.6 (±12.0) years at survey enrollment. Many participants (71%) suspected they had migraine before diagnosis, with 31% reluctant to seek help. Of these, approximately one-third were unaware of treatment, did not think that a physician could do anything more for migraine, would not take them seriously, or were reluctant due to a previous unhelpful experience. Participants mainly received information from friends/family (47%) or the internet (28%). Participants initially sought treatment due to an increase in migraine frequency (77%), attacks interfering with work or school (75%), or increased pain intensity (74%). Subjects saw a mean of 4.1 (±4.3) healthcare providers before migraine diagnosis, and 20% of participants previously received a different diagnosis. Participants reported migraine causes included stress/anxiety/depression (42%), hormonal changes (30%), nutrition (20%), and weather (16%). Acute treatment of migraine included prescription (82%) and over-the-counter (50%) medications, changes in nutrition (62%), adjusting fluid intake (56%), and relaxation techniques (55%). Preventive medications included anticonvulsants (61%), antidepressants (44%), blood pressure-lowering medications (43%), and botulinum toxin A injections (17%). Most discontinuations were due to lack of efficacy or side effects. People with migraine describe reluctance in seeking health care, and misunderstandings seem common especially in the beginning of their migraine journey. Graphical abstract available for this article.

Psychopathological variables in chronic migraine patients with different therapeutic approach: psychological profile differences and impact on therapeutic efficacy in real life

Psychopathological variables in chronic migraine patients with different therapeutic approach: psychological profile differences and impact on therapeutic efficacy in real life

Repetitive transcranial magnetic stimulation in new daily persistent headache patients: a single arm open label study

BackgroundNew daily persistent headache (NDPH) is a continuous, unremitting headache from onset that yields suboptimal results with traditional medicines. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising non-invasive treatment for other headache disorders, such as migraine, and neuromodulation has not been well-studied in NDPH. The objective of the study was to evaluate the efficacy of rTMS in reducing the frequency and severity of headaches, and associated anxiety and depressive symptoms in NDPH patients.MethodsThis was an open label prospective, single arm, interventional pilot study conducted between October 2022 and September 2023. All eligible participants received 10 Hz rTMS (600 pulses, 10 trains), delivered to the left prefrontal cortex for three consecutive days. The post-rTMS headache severity was recorded weekly for four weeks and headache free days/functional disability, PHQ-9, and GAD-7 scores at the end of four weeks and compared with pre-rTMS parameters. The primary outcome was defined by ≥ 50% reduction in headache severity on Visual Analogue Scale (VAS) score, decrease in headache days from the baseline and secondary outcome was ≥ 6 point reduction in HIT-6 score at 4 weeks.ResultsFifty NDPH patients (mean [SD] age, 35.06 [13.91] years; 31 females [62%]) participated in this study. Thirty-five patients (70%) reported ≥ 50% improvement in pain severity (p-value < 0.001), with a mean reduction of 10.84 (4.88) headache days per 28 days from a baseline of 28 headache days (p-value < 0.001). Thirty-eight patients (76%) reported a ≥ 6 point’s reduction in HIT score at 4 weeks. Maximum improvement in the above parameters was observed in NDPH patients with chronic migraine. Two patients reported intolerance to the sound of the rTMS. The median (IQR) PHQ-9 and GAD-7 scores reduced from 11.5(3.75,20) to 7(2,15) (p-value < 0.001) and 10(3,14) to 5.5(0,9) (p-value < 0.001) respectively.ConclusionrTMS was well tolerated and effective in reducing pain severity, headache days and headache related disability, depressive and anxiety symptoms.Trial registrationCTRI/2023/05/053247.

Real-World Evidence of the Safety and Effectiveness of Atogepant Added to OnabotulinumtoxinA for the Preventive Treatment of Chronic Migraine: A Retrospective Chart Review.

Combination use of atogepant and onabotulinumtoxinA has the potential to be more effective than either alone for the preventive treatment of chronic migraine (CM) due to their complementary mechanisms of action. This analysis collected real-world data to evaluate the safety, tolerability, and effectiveness of adding atogepant to onabotulinumtoxinA as a combination preventive treatment for CM. This retrospective, longitudinal, multicenter chart review included adults with CM who received ≥ 2 consecutive cycles of onabotulinumtoxinA before ≥ 1month of onabotulinumtoxinA and atogepant combination treatment. Charts at atogepant prescription (index date) and two subsequent onabotulinumtoxinA treatment visits (~ 3 and ~ 6 months post-index) were reviewed for change from baseline in monthly headache days (MHDs), ≥ 50% reduction in MHDs, discontinuation rates, and adverse events (AEs). Of the 55 charts that met safety analysis criteria, 31 had data on headache days at index and first post-index visit and were eligible for effectiveness analysis (mean age 46.7years, 94.5% female). For those with data available prior to onabotulinumtoxinA treatment (n = 25), the mean MHD was 24.0 days, reduced by 8.15 days after onabotulinumtoxinA treatment. After atogepant was added, MHD was incrementally reduced by 4.53 days and 8.75 days from index date to the first (N = 31) and second (N = 23) post-index onabotulinumtoxinA treatment visit, respectively. A ≥ 50% reduction in MHDs was achieved by 45.2% of patients ~ 3months post-index. Atogepant and onabotulinumtoxinA were discontinued by 16.1% and 6.5% of patients, respectively. In the safety population, 32.7% of patients experienced ≥ 1 AE. No serious AEs were reported. This real-world study of patients with CM demonstrated that adding atogepant to onabotulinumtoxinA as a combination preventive treatment for CM was effective by providing an additional reduction in MHDs over ~ 3 and ~ 6months of combination treatment. Safety results were consistent with the known safety profiles of onabotulinumtoxinA and atogepant, with no new safety signals identified.

Trends in the prevalence and pharmacological management of migraine during pregnancy in the UK, 2000–2018

BackgroundMigraine is common in women of reproductive age. This study aimed to (1) describe the prevalence of migraine in pregnant women in the UK, (2) identify drugs commonly prescribed for...

"Code Headache": Development of a protocol for optimizing headache management in the emergency room.

Patients presenting at the emergency room (ER) with headache often encounter a hostile atmosphere and experience delays in diagnosis and treatment. The aim of this study was to design a protocol for the ER with the goal of optimizing the care of patients with urgent headache to facilitate diagnosis and expedite treatment. A narrative literature review was conducted via a MEDLINE search in October 2021. The "Code Headache" protocol was then developed considering the available characteristics and resources of the ER at a tertiary care center within the Spanish National Public Health system. The Code Headache protocol comprises three assessments: two scales and one checklist. The assessments identify known red flags and stratify patients based on suspected primary/secondary headaches and the need for pain treatment. Initial assessments, performed by the triage nurse, aim to first exclude potentially high morbidity and mortality etiologies (HEAD1 scale) and then expedite appropriate pain management (HEAD2 scale) based on scoring criteria. HEAD1 evaluates vital signs and symptoms of secondary serious headache disorders that can most benefit from earlier identification and treatment, while HEAD2 assesses symptoms indicative of status migrainosus, pain intensity, and vital signs. Subsequently, ER physicians employ a third assessment that reviews red flags for secondary headaches (grouped under the acronym 'PEACE') to guide the selection of complementary tests and aid diagnosis. The Code Headache protocol is a much needed tool to facilitate quick clinical assessment and improve patient care in the ER. Further validation through comparison with standard clinical practice is warranted.

Efficacy and Safety of Erenumab for Nonopioid Medication Overuse Headache in Chronic Migraine

Patients with chronic migraine and medication overuse headaches (CM-MOH) represent a particularly burdened subpopulation. This trial provides first, to our knowledge, American Academy of Neurology class I evidence for a preventive therapy in CM-MOH. To assess erenumab efficacy and safety in patients with nonopioid CM-MOH. This randomized, double-blind, parallel-group, placebo-controlled trial took place at 67 centers in North America, Europe, and Australia from October 7, 2019, to November 2, 2022. This report reflects the primary analysis conducted in January 2023, using a database snapshot from December 1, 2022, which contains the complete dataset of the double-blind treatment period (DBTP). Participants included adults with CM-MOH who had 1 or more preventive treatment failure(s). There were 992 participants screened and 620 participants enrolled (584 in nonopioid cohort and 36 in opioid cohort). Erenumab, 70 mg, 140 mg, or placebo, once monthly for 24 weeks. The primary end point was MOH remission at month 6. Secondary end points included change from baseline in mean monthly acute headache medication days (AHMD) at month 6 and sustained MOH remission throughout the DBTP. Safety end points were adverse events and changes in vital signs. The primary analysis population included 584 participants in the nonopioid-treated cohort with a mean age of 44 years and 482 participants were female (82.5%). Baseline demographics and disease characteristics were balanced across groups. At month 6, 134 participants in the erenumab, 140 mg group (69.1%) (odds ratio [OR], 2.01; 95% CI, 1.33-3.05; P < .001 vs placebo) and 117 in the erenumab, 70 mg group (60.3%) (OR, 1.37; 95% CI, 0.92-2.05; P = .13 vs placebo) achieved MOH remission vs 102 participants in the placebo group (52.6%). AHMD use was also reduced in the erenumab groups vs placebo. Least squares mean (standard error) change from baseline in average monthly AHMD was -9.4 (0.4) days in the erenumab, 140 mg group (difference from placebo, -2.7; 95% CI, -3.9 to -1.6; P < .001) and -7.8 (0.4) days in the erenumab, 70 mg group (difference from placebo, -1.2; 95% CI, -2.4 to -0.1; P = .03), vs -6.6 (0.4) days in the placebo group. MOH remission throughout the DBTP was sustained in 119 participants (61.3%,) 96 participants (49.5%), and 73 participants (37.6%) in the erenumab, 140 mg, 70 mg, and placebo groups, respectively. Adverse events were consistent with the known safety profile of erenumab. Treatment-emergent adverse events incidence in the combined erenumab group was 66.8% (259 participants; constipation 15.2% (59 participants) and COVID-19 13.9% (54 participants) were most common. In this study, monthly, 140 mg, erenumab injections safely and effectively achieved MOH remission in patients with nonopioid CM-MOH within 6 months. ClinicalTrials.gov Identifier: NCT03971071.

Persistence, effectiveness, and tolerability of anti-calcitonin gene-related peptide monoclonal antibodies in patients with chronic migraine.

To evaluate, in patients with chronic migraine (CM) in real-world conditions, the persistence, effectiveness, and tolerability of erenumab, fremanezumab, and galcanezumab anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies (mAbs) and the persistence and effects of switching. Anti-CGRP mAbs represent a novel therapeutic approach to the management of CM; however, real-world data on persistence, effectiveness, and tolerability, especially after switching, are scarce. This was a retrospective observational cohort study including all patients with CM treated with erenumab, fremanezumab, and/or galcanezumab in a tertiary hospital between January 2019 and December 2022. Treatment persistence was measured as the number of days between treatment start and end dates or the end of follow-up and also as a percentage of persistent patients at 3, 6, and 12 months; effectiveness as a ≥50% reduction in monthly migraine days (MMD); and tolerability as the number and type of adverse events. Included were 281 patients (383 treatments) with CM (91.5% [257/281] female) receiving anti-CGRP mAbs. Median (interquartile range [IQR]) treatment persistence was 267 (103-550) days. At 12 months, persistence was greater for the first (66.7%) compared to the second (49.8%) and third (37.2%) anti-CGRP mAb treatments (hazard ratio [HR] = 1.93, 95% confidence interval [CI]: 1.35-2.74; HR = 2.75, 95% CI: 1.69-4.47, respectively). Persistence minimum observed median (IQR) was also greater for the first (291 [112-594] days) compared to both the second (188 [90-403] days; p < 0.001) and third (167 [89-352] days; p < 0.001) anti-CGRP mAb treatments. For the first anti-CGRP mAb treatment, there were no differences in persistence among the different drugs. In terms of effectiveness of the first, second, and third anti-CGRP mAb treatments, a ≥50% reduction in MMD was achieved by 57.6% (117/203), 25.0% (11/44), and 11.8% (2/17) of patients, respectively, at 3 months, and by 55.8% (87/156), 29.6% (8/27), and 12.5% (1/8) of patients, respectively, at 6 months. At 12 months, no significant effectiveness differences were observed among anti-CGRP mAb treatments. As for tolerability, 55 adverse events were reported by 43 (15.3%) patients, mostly mild and leading to treatment discontinuation in only 14 (5.0%) patients. The most common adverse events were constipation, injection site reaction, and pruritus. Erenumab patients (3%, 3/99) experienced a higher rate of discontinuation for constipation. Our findings showed a 12-month higher treatment persistence with the use of a first anti-CGRP mAb treatment when the switch to a second treatment was due to ineffectiveness or severe side events. This persistence was lower after a second or third anti-CGRP. Additionally, in terms of effectiveness, the first anti-CGRP treatment achieved a higher response in terms of ≥50% reduction in MMD; however, some patients may benefit from a switching strategy. Finally, the tolerability profile for anti-CGRP mAbs was favorable. Further studies are needed to identify predictors of response after switching from the first anti-CGRP mAb treatment.

The impact of botulinum toxin on the health, physical condition, and mental well-being of individuals suffering from chronic migraines

The impact of botulinum toxin on the health, physical condition, and mental well-being of individuals suffering from chronic migraines

Predictors of migraine interictal burden: The hidden role of subjective memory complaints.

The "interictal burden of migraine" (MIB) is a new concept that encompasses the overall impact of the disease between migraine episodes. However, the factors that contribute to this interictal burden are still unclear. This study aimed to identify explanatory factors of interictal burden in patients with migraine. This prospective cross-sectional observational including 200 patients with migraine (92% [n = 184] female, with a mean [standard deviation] age of 44.8 [12] years, 53% [n = 106] with chronic migraine) completed a clinical and questionnaire assessment targeting MIB, migraine impact, and depressive and cognitive complaints. More than three-fourths (76% [n = 152]) of patients had moderate-to-severe interictal burden. Higher interictal burden (MIB Scale ≥2) was associated with higher headache frequency (eight vs. 14, p = 0.001) and intensity (headache index score 17.0 vs. 30.0, p = 0.002), higher headache impact (six-item Headache Impact Test score 59.2 vs. 63.9, p = 0.001), and more subjective memory complaints (Subjective Memory Complaints Questionnaire [SMC] score 9.0 vs. 4.5, p = 0.001), as well as anxiety (Hospital Anxiety and Depression Scale (HADS)-Anxiety score 5 vs. 10, p < 0.001) and depression symptoms (HADS-Depression score 5 vs. 8, p < 0.001). Once accounted for these potential explanatory variables, subjective memory complaints and impact of headache during ictal phase remained as individual determinants of the interictal burden, with SMC explaining 15% (odds ratio 1.15, 95% confidence interval 1.03-1.28; p = 0.010) of the interictal burden. This finding highlights the need to consider cognitive complaints as part of the construct of interictal burden of these patients to refine the focus of their management.

Individuals With Chronic Migraine Present Changes in The Electromyographic Signal Oh The Head and Neck Flexors

Individuals With Chronic Migraine Present Changes in The Electromyographic Signal Oh The Head and Neck Flexors

Recent Development of Zolmitriptan Formulation in Migraine Therapy: Production, Metabolism and Pharmaceutical Aspects.

The triptans class of pharmaceuticals, which was created to treat acute migraine, is made up of indole-containing drugs that bind to a subset (1B/1D) of 5-hydroxytryptamine receptors and are agonists of serotonin receptors. At the moment, naratriptan, eletriptan, zolmitriptan, rizatriptan, almotriptan, and frovatriptan are the seven types of triptans available on the market. Among these are the FDA-approved triptans, Zolmitriptan and Sumatriptan, which are selective serotonin (5-hydroxytryptamine) agonists. Zolmitriptan, a synthetic tryptamine derivative and a well-known member of the triptan family, is available as an orally disintegrating tablet, nasal spray, and tablet. There are melt formulations of rizatriptan and zolmitriptan available on the market that are easier to use and absorb, comparable to regular pills. Recently, the FDA approved zolmitriptan, a medication with tolerability comparable to sumatriptan. Whereas zolmitriptan is only available as an oral melt or tablet, sumatriptan is available as a nasal spray, oral preparation, or self-injectable kit. The only known antimigraine drugs that were widely utilized before the triptan period were ergotamine and dihydroergotamine. However, zolmitriptan binds to plasma proteins only 25% of the time because of significant first-pass degradation. Researchers have looked into fresh ideas for solving this issue and innovations to overcome its pharmacokinetic difficulties. This article emphasizes the role of zolmitriptan in the treatment of migraines, highlighting its pharmacological properties, production, metabolism, and structural features.

Genetic variants associated with response to anti-CGRP monoclonal antibody therapy in a chronic migraine Han Chinese population

BackgroundAnti-calcitonin gene-related peptide (CGRP) monoclonal antibodies have emerged as promising therapeutic options for the treatment of chronic migraine. However, treatment response varies considerably among individuals, suggesting a potential role for genetic factors. This study aimed to identify genetic variants affecting the efficacy of anti-CGRP monoclonal antibody therapy in chronic migraine among the Han Chinese population in Taiwan to enhance treatment precision and to understand the genetic architecture of migraine.MethodsWe conducted a quantitative trait locus (QTL) association study in patients with chronic migraines from a tertiary medical center in Taiwan using the Taiwan Precision Medicine Array Chip. The patients received fremanezumab or galcanezumab for at least 12 weeks. Treatment efficacy was assessed based on the improvement rate in monthly migraine days. Genetic variants were identified, and their associations with treatment efficacy were examined through quantitative trait loci analysis, linkage disequilibrium studies, and functional annotations using the Gene Ontology database.ResultsSix single nucleotide polymorphisms (SNPs) relative variants were significantly associated with anti-CGRP therapy response (p < 1 × 10− 7): rs116870564, rs75244870, rs56216870, rs12938101, rs74655790, and rs149540851. These variants are located in or near genes, including LRRC4C, ATAD2B, and OXR1, which are involved in neuronal development, DNA-dependent ATPase activity, and oxidation-reduction processes, respectively. The rs116870564 variant in LRRC4C showed the strongest association (β = -0.551, p = 6.65 × 10− 9). The functional impact of these variants is attributed to their regulatory effects on gene expression, which are influenced by intron splicing regulation, transcription factors, and changes in chromatin structure.ConclusionThe identification of key genetic markers associated with response to anti-CGRP therapy emphasizes the importance of genetic variability in treatment efficacy. This could lead to more personalized chronic migraine management strategies and tailored therapeutic approaches based on individual genetic profiles. Further research in larger, diverse populations is warranted to validate these findings and refine our understanding of the role of CGRP in chronic migraine pathophysiology.Trial registrationNot applicable.

Alpha-asarone alleviates cutaneous hyperalgesia by inhibiting hyperexcitability and neurogenic inflammation via TLR4/NF-κB/NLRP3 signaling pathway in a female chronic migraine rat model

Migraine is a highly prevalent neurological disorder. Alpha-asarone (ASA), a major active component found in Acorus tatarinowii, plays a crucial role in analgesia and anti-inflammation for neuropathic pain. This study aimed to assess the efficacy of ASA against migraine and elucidate its potential mechanisms using a well-established inflammatory soup (IS) migraine female rat model. Mechanical pain thresholds were assessed daily before IS infusion, followed by post-infusion administration of ASA. Subsequently, spontaneous locomotor activities, exploratory behavior, short-term spatial memory, and photophobia were blindly evaluated after the final drug administration. The rats were then sacrificed for investigation into the underlying mechanisms of action. Network pharmacology was also employed to predict potential targets and pathways of ASA against migraine. The anti-inflammatory activity of ASA and pathway-related proteins were examined in BV2 cells stimulated with lipopolysaccharides (LPS). The results demonstrated that ASA ameliorated cutaneous hyperalgesia and photophobia while improving spatial memory and increasing exploratory behavior in IS rats. ASA attenuated central sensitization-related indicators and excessive glutamate levels while enhancing GABA synthesis. ASA rescued neuronal loss in the cortex and hippocampus of IS rats. Notably, the ability of ASA to improve spatial memory performance in the Y maze test was not observed with sumatriptan, a first-line treatment drug, suggesting the potential involvement of the TLR4 pathway. Moreover, ASA suppressed microglial activation, reduced pro-inflammatory factors, and downregulated TLR4, MyD88, p–NF–κB/NF-κB, NLRP3, caspase-1, IL-1β, and IL-18. Overall, ASA demonstrated its potential to alleviate hyperalgesia and improve behavioral performance in migraine rats by inhibiting hyperexcitability and microglia-related inflammation.

Effectiveness of combining greater occipital nerve block and pulsed radiofrequency treatment in patients with chronic migraine: a double-blind, randomized controlled trial

BackgroundPulsed radiofrequency (PRF) treatment targeting the greater occipital nerve (GON) has shown efficacy in treating various conditions. This double-blind, randomized controlled study aimed to evaluate the effects of combining PRF therapy with GON block (GONB) therapy in patients with chronic migraine.MethodsThe study consisted of two groups: GONB and GONB + PRF, each comprising 16 patients with chronic migraine. Using 0.5-Hz sensorial stimulation, a 5-cm-long radiofrequency needle was inserted under ultrasound guidance in both groups. Subsequently, all patients received a GONB by administering 2 mL of 0.25% bupivacaine. In the GONB + PRF group, patients underwent 4 min of PRF at 42℃, whereas the GONB group did not receive any PRF treatment. Follow-up examinations were performed at 1, 2, 3 and 6 months after the procedure to evaluate the frequency and severity of migraine attacks, number of headache days, and analgesic consumption.ResultsIn the GONB + PRF group, the visual analog scale (VAS) score, number of migraine attacks, number of headache days, and analgesic consumption were significantly lower compared to the GONB group (P < 0.05). Significant decreases (60%) in mean VAS scores, number of migraine attacks, number of headache days, and consumption of analgesic medications were observed in the GONB + PRF group at the 1-, 2-, 3-, and 6-month follow-ups compared with the pre-treatment period (P < 0.05).ConclusionsThe combination of GONB and PRF presents a promising new treatment option for patients with chronic migraine. This approach has demonstrated efficacy in minimizing analgesic use, decreasing the frequency of migraine attacks, reducing the number of headache days and decreasing the severity of migraine attacks.Trial RegistrationNCT05464212.

Proteome-wide Mendelian randomization identified potential drug targets for migraine

BackgroundMigraine is a highly prevalent and complex neurovascular disease. However, the currently available therapeutic drugs often fall to adequately meet clinical needs due to limited effectiveness and numerous undesirable side effects. This study aims to identify putative novel targets for migraine treatment through proteome-wide Mendelian randomization (MR).MethodsWe utilized MR to estimate the causal effects of plasma proteins on migraine and its two subtypes, migraine with aura (MA) and without aura (MO). This analysis integrated plasma protein quantitative trait loci (pQTL) data with genome-wide association studies (GWAS) findings for these migraine phenotypes. Moreover, we conducted a phenome-wide MR assessment, enrichment analysis, protein–protein interaction networks construction, and mediation MR analysis to further validate the pharmaceutical potential of the identified protein targets.ResultsWe identified 35 protein targets for migraine and its subtypes (p < 8.04 × 10–6), with prioritized targets showing minimal side effects. Phenome-wide MR identified novel protein targets—FCAR, UBE2L6, LATS1, PDCD1LG2, and MMP3—that have no major disease side effects and interacted with current acute migraine medication targets. Additionally, MMP3, PDCD1LG2, and HBQ1 interacted with current preventive migraine medication targets. The causal effects of plasma protein on migraine were partly mediated by plasma metabolites (proportion of mediation from 3.8% to 21.0%).ConclusionsA set of potential protein targets for migraine and its subtypes were identified. These proteins showed rare side effects and were responsible for biological mechanisms involved in migraine pathogenesis, indicating priority for the development of migraine treatments.

Exploring Facial Somatosensory Distortion in Chronic Migraine: The Role of Laterality and Emotion Recognition—A Cross-Sectional Study

Background: In addition to being highly distressing, chronic migraine headaches are a major socioeconomic challenge. Like other pain syndromes, migraine headaches are associated with psychological and physiological impairments, including sensorimotor and somatosensory deficits. Aim: This study aims to explore whether patients with high-frequency or chronic migraine differ from a healthy population in the areas of laterality recognition (LAT) and facial emotion recognition (FER) and whether there are correlations between these areas and central sensitization of pain and psychological components like stress, depression, anxiety, and alexithymia. Methods: Using a cross-sectional design, individuals with high-frequency or chronic (ICHD classification) migraine (migraine group MG = 45) and healthy individuals (control group CG = 25) were studied using LAT testing (hand, neck, and face); FER testing; and questionnaires, including the Central Sensitization Inventory (CSI) and the Toronto Alexithymia Scale (TAS-20). Results: Data from 70 participants were collected for analysis. Statistically significant differences were found only in the assessment of central sensitization (p &lt; 0.001). Weak to moderate monotonic correlations were found for the MG, especially between alexithymia detection (TAS-20) and facial emotion recognition (FER test). Discussion: The methodological procedure and its accompanying challenges can be seen as limitations of this study. The lack of significant effects must be mentioned, but the selection of the collected questionnaires, the uniform diagnostics, and the statistical processing of a large amount of data represent methodological strengths. Conclusion: The CSI and the TAS-20 could be used in combination with FER to assess chronic migraine. Implementing the described sensorimotor parameters as a therapeutic intervention requires further investigation.

Clinical decision support system using hierarchical fuzzy diagnosis model for migraine and tension-type headache based on International Classification of Headache Disorders, 3rd edition.

To determine whether the diagnostic ability of the newly designed hierarchical fuzzy diagnosis method is consistent with that of headache experts for probable migraine (PM) and probable tension-type headache (PTTH). Clinical decision support systems (CDSS) are computer systems designed to help doctors to make clinician decisions by information technology, and have proven to be effective in improving headache diagnosis by making medical knowledge readily available to users in some studies. However, one serious drawback is that the CDSS lacks the ability to deal with some fuzzy boundaries of the headache features utilized in diagnostic criteria, which might be caused by patients' recall bias and subjective bias. A hybrid mechanism of rule-based reasoning and hierarchical fuzzy diagnosis method based on International Classification of Headache Disorders, 3rd edition (ICHD-3) was designed and then validated by a retrospective study with 325 consecutive patients and a prospective study with 380 patients who were clinically diagnosed with migraine and TTH at the headache clinic of Chinese PLA General Hospital. The results of the diagnostic test in the retrospective study indicated that the fuzzy-based CDSS can be used in the diagnosis of migraine without aura (MO) (sensitivity 97.71%, specificity 100%), TTH (sensitivity 98.57%, specificity 100%), PM (sensitivity 91.25%, specificity 98.75%) and PTTH (sensitivity 90.91%, specificity 99.63%). While in the prospective study, the diagnostic performances were MO (sensitivity 91.62%, specificity 96.52%), TTH (sensitivity 92.17%, specificity 95.47%), PM (sensitivity 85.48%, specificity 98.11%) and PTTH (sensitivity 87.50%, specificity 98.60%). Cohen's kappa values for the consistency test were 0.984 ± 0.018 (MO), 0.991 ± 0.018 (TTH), 0.916 ± 0.051 (PM), 0.932 ± 0.059 (PTTH) in the retrospective study and 0.884 ± 0.047 (MO), 0.870 ± 0.055 (TTH), 0.853 ± 0.073 (PM), 0.827 ± 0.118 (PTTH) in the prospective study, which indicated good consistency with the fuzzy-based CDSS and the gold standard (p < 0.001). We developed a fuzzy-based CDSS performs much more similarly to expert diagnosis and performs better than the routine CDSS method in the diagnosis of migraine and TTH, and it could promote the application of artificial intelligence in the area of headache diagnosis.

Predictors of chronic migraine remission

BackgroundChronic migraine is a debilitating neurological condition that significantly impairs both individual and socioeconomic outcomes. The aim of the present study was to estimate the remission rates of chronic migraine to episodic migraine, and to identify potential predictors of chronic migraine remission. In addition, to assess impact of chronic migraine remission on headache related disability.ResultsOut of 300 individuals with chronic migraine (CM) who attended to our institution and continued for follow up in the period from the 1st of January 2021 up to the end of December 2022, approximately 82 cases (27.3%) had remitting CM, while 117 cases (39.0%) had persistent CM, and 101 cases (33.7%) had transitional CM. On multivariate model for detection of potential predictors of CM remission revealed that patients with lowest headache frequency (15–19 frequency/month) were much more likely to remit (OR = 577.826, 95% CI: 15.259 to 21,881.228, P = 0.001) than those with high-frequency CM (25–30 frequency/month), patients with non CM with allodynia (0–2) were more likely to remit (OR = 139.374, 95% CI: 4.634 to 419.879, P = 0.004) compared to those with moderate to severe CM with allodynia (≥ 6). Additionally, those using Topiramate or beta-blockers were more likely to achieve remission (OR = 23.325, 95% CI: 3.289 to 165.400, P = 0.002, and OR = 34.205, 95%CI: 3.591 to 325.842, P = 0.002, respectively), and also non-smokers were 11 times more likely to achieve remission compared to smokers (OR = 11.370, 95% CI: 1.702 to 75.934, P = 0.012).ConclusionThese findings identified several potential predictors of remission among patients with chronic headache. However, the majority of these prognostic factors are modifiable.