Migraine Research Articles

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.

The association between dietary antioxidant quality score and intensity and frequency of migraine headaches among women: a cross-sectional study

BackgroundMigraine is an episodic disorder and a frequent form of headache. An impaired balance between free radical production and an impaired antioxidant defense system leading to oxidative damage may play a major role in migraine etiology. We sought to investigate whether dietary antioxidant quality score (DAQS) is associated with migraine intensity and frequency among women suffering from migraine.MethodsThis cross-sectional study was conducted on 265 women. The data related to anthropometric measures and dietary intake were collected. DAQS score was calculated based on FFQ (food frequency questionnaire) vs. the reference daily intake (RDI) quantity. To measure migraine intensity, the migraine disability assessment questionnaire (MIDAS) and visual analog scale (VAS) were used. The frequency of headaches was defined as the days the participants had headaches in the last month and a 30-day headache diary was used.ResultsThe results of the study demonstrated that VAS, MIDAS, and frequency of headaches were reduced significantly from the low DAQS (poor quality of antioxidants) to high DAQS (high quality of antioxidants) after adjusting covariates. Also, multinomial regression showed there was an inverse association between higher DAQS and the frequency of headaches. In the adjusted model, subjects with the higher DAQS were 69% less likely to have moderate migraine disability, compared with those with the lower DAQS. Linear regression showed, there was an inverse association between vitamin C intake and the grades of pain severity.َAlso in a crude model, a negative association was found between vitamin E and the frequency of headaches.ConclusionIn conclusion, Participants with higher DAQS had lower migraine intensity and headache frequency. In addition, the consumption of vitamin C may potentially associate with decreasing the severity of headaches. Dietary antioxidants should be monitored closely in individuals suffering from migraine.

Case Series and Literature Review of Up-to-date Surgical Management of Occipital Neuralgia.

Nerve decompression is an emerging surgical treatment option for patients with occipital neuralgia. However, limited research is available on the efficacy of this treatment in South Korea. This retrospective study evaluates the efficacy of nerve decompression surgery in patients with chronic migraines, specifically focusing on occipital neuralgia, in South Korea. Between January 2019 and December 2022, six patients diagnosed with occipital neuralgia, who had not responded to conservative treatments, underwent nerve decompression surgery. This procedure, performed under local anesthesia, involved decompression of the greater and/or lesser occipital nerves. Patient data were analyzed for headache frequency and intensity (using the Numeric Rating Scale [NRS]) and the decrease in oral medications needed postsurgery. Results showed significant improvement in headache symptoms postsurgery, with the average preoperative NRS score of 7.9 dropping to 3.7 postoperatively. Additionally, the average number of medications used decreased from 3.2 to 1.3. No significant surgical complications were reported. The study highlights the potential of nerve decompression as an effective treatment for occipital neuralgia, particularly in cases resistant to traditional medical management.

Changes in use of acute and preventive medications for migraine after erenumab initiation over 12 months: A United States retrospective cohort study.

To assess changes in real-world use of acute and preventive medications for migraine over a 12-month follow-up period in the United States following initiation of the anti-calcitonin gene-related peptide (CGRP) pathway monoclonal antibody (mAb) erenumab. Early assessments of real-world use of acute and preventive medications for migraine after initiation of erenumab have been limited to 6 months of follow-up. This retrospective cohort study used data from the IQVIA open-source longitudinal prescription (LRx) and medical (Dx) claims databases. Adult patients with an initial claim (index date) for erenumab between May 2018 and April 2020 were identified. Among 201,176 patients who met inclusion criteria, the mean (standard deviation [SD]) age was 47.5 (13.8) years and 85.6% (n = 172,153) were female. Most patients used one or more acute (88.4%; n = 177,795) and one or more traditional preventive (86.1%; n = 173,225) medications during the 12-month pre-index period. Adherence to erenumab (proportion of days covered [PDC] ≥0.80) was 40.2% (n = 80,927) with an overall mean (SD) PDC of 0.60 (0.34). Among all patients, 70.0% (n = 140,809) discontinued erenumab. After accounting for 24.7% (n = 49,720) of patients who restarted erenumab, discontinuation without reinitiation was observed in 45.3% (n = 91,089) of total patients. Switching to a different anti-CGRP pathway mAb was observed in 13.1% (n = 26,446) of total patients. Among 177,795 patients with pre-index use of one or more acute migraine medication class, 86.5% (n = 153,788) had post-index use of the same class, and 56.7% (87,134/153,788) of them discontinued one or more class of acute medication in the 12-month follow-up period. Similarly, among 173,225 patients with pre-index use of one or more traditional migraine preventive medication class, 67.7% (n = 117,274) had post-index use of the same class, and 46.7% (54,790/117,274) of them discontinued one or more class of traditional preventive medication in the 12-month follow-up period. In this long-term study, we observed the discontinuation of both acute and preventive medications for migraine post-erenumab initiation.

Cost per treatment responder analysis of atogepant compared to rimegepant for the preventive treatment of episodic migraine.

To estimate the number needed to treat and cost per additional responder for atogepant and rimegepant versus placebo for the preventive treatment of episodic migraine (EM) in the United States. Migraine has an enormous impact on a person's daily activities and quality of life, and results in significant clinical and economic burden to both individuals and society. It is important to understand the comparative efficacy and economic value of oral calcitonin gene-related peptide receptor antagonists (gepants) for preventive treatment of EM. Currently, atogepant and rimegepant are US Food and Drug Administration approved for preventive treatment of migraine (rimegepant for EM and atogepant for EM and for chronic migraine). In the absence of head-to-head trials, we utilized an indirect treatment comparison on efficacy data from clinical trials conducted for the preventive treatment of EM. We estimated number needed to treat, a valuable metric used in clinical practice to compare treatment efficacy, and cost per additional responder, which can be used to establish the cost effectiveness of a treatment. An indirect treatment comparison was conducted to compare the efficacy of atogepant 60 mg once daily and rimegepant 75 mg once every other day as preventive treatments for EM using published data from the registrational trials of atogepant (ADVANCE) and rimegepant (BHV3000-305). The efficacy outcome of interest was ≥50% reduction from baseline in mean monthly migraine/headache days (≥50% responder rate), which was variably defined for a base case and two scenario analyses. Number needed to treat and cost per additional responder versus placebo were calculated and compared between both treatments (weeks 9-12 in the base case analysis; weeks 1-12 and 9-12 for atogepant and during weeks 9-12 for rimegepant in the scenario analyses). In the base case analysis, ≥50% responder rates were 64.9% (95% confidence interval [CI], 53.9-74.5) for atogepant and 51.8% (95% CI, 42.9-60.6) for rimegepant, compared to 44.1% (95% CI, 39.4-49.0) for placebo. The median number needed to treat versus placebo in the base case scenario was 4.8 (95% CI, 3.1-9.0) for atogepant compared to 13.0 (95% CI, 5.9-75.1) for rimegepant. The cost per additional responder versus placebo in the base case scenario was estimated to be $15,823 (95% CI, $11,079-$29,516) for atogepant compared to $73,029 (95% CI, $32,901-$422,104) for rimegepant. Results of the two scenario analyses were consistent with the base case analysis. Atogepant had substantially lower numbers needed to treat and costs per additional responder versus placebo than rimegepant for the preventive treatment of EM across all evaluated scenarios. These analyses suggest that atogepant may be more cost effective than rimegepant for the preventive treatment of EM. Limitations include differences in inclusion/exclusion criteria and in reporting of the ≥50% responder rates between trials.

Transcriptomic changes in the hypothalamus of mice with chronic migraine: Activation of pathways associated with neuropathic inflammation and central sensitization

Chronic migraine is a common central nervous system disorder characterized by recurrent, pulsating headaches. However, the extent and mechanisms of hypothalamic involvement in disease progression have not been thoroughly investigated. Herein, we created a chronic migraine mouse model using repeated intraperitoneal injections of nitroglycerin. We performed transcriptomic sequencing on the hypothalamus of mice with chronic migraine and control mice under normal physiological conditions, followed by differential gene set enrichment and functional analysis of the data. Additionally, we examined the intrinsic connection between chronic migraine and sleep disorders using transcriptomic sequencing data from sleep-deprived mice available in public databases. We identified 39 differentially expressed genes (DEGs) in the hypothalamus of a mouse model of chronic migraine. Functional analysis of DEGs revealed enrichment primarily in signaling transduction, immune-inflammatory responses, and the cellular microenvironment. A comparison of the transcriptomic data of sleep-deprived mice revealed two commonly expressed DEGs. Our findings indicate that the hypothalamic DEGs are primarily enriched in the PI3K/AKT/mTOR pathway and associated with the NF-κB/NLRP3/IL-1 β pathway activation to maintain the central sensitization of the chronic migraine. Chronic migraine-induced gene expression changes in the hypothalamus may help better understand the underlying mechanisms and identify therapeutic targets.

Relationship of myofascial trigger points with related disability, anxiety, and depression in patients with migraine headaches

BackgroundMigraine affects one in ten individuals worldwide and is the second leading cause of disability. Studies have shown an association between migraine and the musculoskeletal system, and myofascial trigger points (MTrPs) play an essential role. Additionally, those with myofascial pain have been proven to experience higher levels of depression and anxiety. Understanding the association between MTrPs and migraine is crucial for developing targeted treatment strategies. Additionally, recognizing the link between MTrPs and migraine-related depression and anxiety underscores the importance of a holistic approach to migraine management. By addressing both musculoskeletal and neurological factors, healthcare providers can provide more effective and personalized care for migraine patients. This study aims to determine the association between MTrPs with migraine-related disability, anxiety, depression, and migraine characteristics.MethodsThis cross-sectional study included 68 migraine patients from an outpatient neurology clinic. The number of MTrPs was determined through examination by an experienced neurologist during a migraine-free period using the recommended international criteria. We evaluated anxiety and depression with the Hospital Anxiety and Depression Scale (HADS) and disability with the Migraine Disability Assessment Scale (MIDAS).ResultsWe enrolled 68 patients (22 males) with a mean age of 36.23 ± 9.63 years. The mean number of MTrPs was 2.75 ± 2.934. MTrPs were positively correlated with severity (CC: 0.576, P-value < 0.001). There was no association between MTrPs and HADS-D or MIDAS, but migraine patients with abnormal HADS-A scores had more MTrPs than patients with normal HADS-A scores (0.6 ± 0.84 vs 3.56 ± 3.11, P-value:0.013).ConclusionsThe number of MTrPs is associated with higher anxiety levels and headache intensity. Further research could investigate the impact of MTrP-based therapies on anxiety among individuals suffering from migraines.

Comparison of two methods of greater occipital nerve block in patients with chronic migraine: ultrasound-guided and landmark-based techniques

BackgroundMigraine is a primary headache defined as moderate-to-severe pain lasting 4 to 72 h, ranking 2nd among the disabling conditions for both genders regardless of the age and the greater occipital nerve (GON) block has been reported as an efficient treatment method for migraine. The present study aims to evaluate and compare the efficiency of the two methods of GON block, i.e., the ultrasound (US)-guided technique and the landmark-based technique.MethodHaving a prospective and randomized design, the study assigned the patients with chronic migraine into two groups after which a neurologist performed landmark-based GON block in the first group while an algologist performed US-guided GON block in the second group. During the 3-month follow-up period, the number of days with pain, the duration of pain, the number of analgesic drugs taken in a month, and Visual Analogue Scale (VAS) scores were compared with the values ​​before treatment and at the 1st week, 1st month, and 3rd month after treatment.ResultsUS-guided GON block group included 34 patients while there were 32 patients in the landmark-based GON block group. US-guided GON block group showed significantly reduced VAS scores and frequency of attacks compared to the landmark-based GON block group at Month 1 after the procedure. After a 3-month follow-up period of the two groups, the frequency of attacks, analgesic intake and the duration of attacks were lower in both groups compared to the baseline. At 3-month follow-up, the mean of VAS scores decreased from 9,47 ± 2,69 to 4,67 ± 1,9 in US-guided GON block group and from 9,46 ± 0,98 to 7 ± 2,5 in the landmark-based GON block group.ConclusionIt was determined that both US-guided and landmark-based GON block were efficient techniques in patients with chronic migraine. US-guided GON block technique resulted in lower VAS scores, shorter durations of pain, lower frequencies of attack, and lower intake of analgesics compared to the landmark-based GON block technique.

The effect of physical therapy integrated with pharmacotherapy on tension-type headache and migraine in children and adolescents

BackgroundTension-type headache (TTH) and migraine are prevalent neurological conditions in children and adolescents that significantly impact activity of daily living (ADL) and quality of life (QOL). Although physical therapy targeting cervical myofascial trigger points (MTrPs) on TTH and migraine has been extensively studied in adults, the efficacy in pediatric patients remains unexplored. The aim of this study is to reveal the effect of physical therapy integrated with pharmacotherapy on TTH and migraine in children and adolescents.MethodsWe conducted a prospective, observational cohort study recruiting consecutive patients aged 6 to 18 years with TTH and migraine with cervical MTrPs. They were classified into 4 types of headaches: frequent episodic TTH (FRTTH), chronic TTH (CTTH), episodic migraine (EM) and chronic migraine (CM). The once-weekly 40-minutes physical therapy session integrated with pharmacotherapy (integrated physical therapy) was continued until the treatment goals (headache days per week less than 2 days, headache impact test-6 (HIT-6) score to below of 50, and the ability to attend school daily) was achieved. Multifaceted assessments including headache frequency (headache days per week), headache intensity using the Visual Analogue Scale (VAS), pain catastrophizing score (PCS), hospital anxiety and depression scale (HADS) score, HIT-6 scores, and EuroQol 5 dimensions 5-level questionnaire (EQ-5D-5 L) scores, were conducted to evaluate the treatment effects.Results161 patients were enrolled in this study. 106 patients (65.8%) were diagnosed with TTH: 70 (66.8%) with FETHH, 36 (34.0%) with CTTH, and 55 patients (34.2%) were diagnosed with migraine: 43 patients (78.2%) with EM, 12 patients (21.8%) with CM. We observed significant improvements in headache frequency, headache intensity, PCS, HADS score, HIT-6 scores, and EQ-5D-5 L scores before and after the treatment in all 4 types of headaches. The average number of sessions required to achieve the treatment goals was 4 times (weeks) for patients with FETTH and EM, 5.5 for those with CTTH, and 7.5 for those with chronic migraine.ConclusionThe integrated physical therapy on pediatric TTH and migraine patients with the cervical MTrPs was significantly effective in reducing headache symptoms and improving ADL and QOL.

Idiopathic intracranial hypertension in Asians: a retrospective dual-center study

BackgroundThere have been limited data on idiopathic intracranial hypertension (IIH) in Asians and there remain uncertainties whether a cerebrospinal fluid (CSF) pressure of 250 mm CSF is an optimum diagnostic cutoff. The aims of the present study included (1) characterization of IIH patients in Taiwan, (2) comparisons among different diagnostic criteria for IIH, and (3) comparisons between patients with CSF pressures of > 250 and 200–250 mm CSF.MethodsThis retrospective study involved IIH patients based on the modified Dandy criteria from two tertiary medical centers in Taiwan. Clinical manifestations were retrieved from electronic medical records, and findings on ophthalmologic examination and magnetic resonance images (MRIs) were reviewed.ResultsA total of 102 patients (71 F/31 M, mean age 33.4 ± 12.2 years, mean CSF pressure 282.5 ± 74.5 mm CSF) were identified, including 46 (45.1%) with obesity (body-mass index ≥ 27.5), and 57 (62.6%) with papilledema. Overall, 80 (78.4%), 55 (53.9%), 51 (50.0%), and 58 (56.9%) patients met the Second and Third Edition of International Classification of Headache Disorders, Friedman, and Korsbæk criteria, respectively. Patients in the 200–250 mm CSF group (n = 40) were less likely to have papilledema (48.5% vs. 70.7%, p = 0.035), transient visual obscuration (12.5% vs. 33.9%, p = 0.005), and horizontal diplopia (10.0% vs. 30.6%, p = 0.006), and had fewer signs on MRIs (2.2 ± 1.3 vs. 2.8 ± 1.0, p = 0.021) when compared with those with CSF pressures > 250 mm CSF (n = 62). However, the percentages of patients with headache (95.0% vs. 87.1%, p = 0.109) at baseline, chronic migraine at six months (31.6% vs. 25.0%, p = 0.578), and visual field defect (86.7% vs. 90.3%, p = 0.709) were similar.ConclusionsIt was found that obesity and papilledema were less common in Asian IIH patients when compared with Caucasian patients. Although patients with CSF pressures of 200–250 mm CSF had a less severe phenotype, the risks of having headache or visual loss were comparable to those in the > 250 mm CSF group. It is possible that a diagnostic cutoff of > 200 mm CSF could be more suitable for Asians, although further studies are still needed.

Unravelling Migraine Stigma: A Comprehensive Review of Its Impact and Strategies for Change.

Migraine-related stigma is a pervasive issue impacting nearly half of chronic migraine patients, with significant consequences for their quality of life, disability and mental health. Despite its profound effects, migraine stigma remains under-recognised in both clinical practice and research. This narrative review explores the three primary types of stigmas affecting migraine patients: public, structural and internalised. Public stigma involves negative societal attitudes and stereotypes that trivialise the condition. Structural stigma is reflected in policies that restrict access to necessary care and resources. Internalised stigma occurs when patients absorb these negative views, leading to self-blame and diminished self-worth. Addressing these different types of stigmas is crucial for improving the understanding, diagnosis and treatment of migraine. Educational efforts, advocacy and policy reform are essential strategies in this context. A deep understanding of stigma is vital for developing effective interventions that enhance clinical management and patient quality of life. Ultimately, reducing stigma can lead to better health outcomes and a more comprehensive approach to migraine care.

Eicosapentaenoic acid versus placebo as adjunctive therapy in chronic migraine: A randomized controlled trial.

This study was conducted to assess the efficacy of daily 2000 mg eicosapentaenoic acid (EPA) supplementation in individuals with chronic migraine. Chronic migraine is characterized by a minimum of 15 headache days/month, necessitating a focus on preventive treatment strategies. EPA, a polyunsaturated fatty acid recognized for its anti-inflammatory properties, is examined for its potential effectiveness in chronic migraine management. A randomized, blinded, placebo-controlled trial of eligible participants with a confirmed diagnosis of chronic migraine were enrolled. The intervention group received 1000 mg of EPA twice daily for 8 weeks, while the control group received two placebo softgels. Symptoms were recorded at 4 and 8 weeks. The primary outcome was assessed using the Headache Impact Test-6 to evaluate changes in patients. Secondary outcomes encompassed migraine headache days, headache severity measured via a visual analog scale, and the number of consumed painkillers. Descriptive analyses were reported in mean (± standard deviation [SD]). A total of 60 patients were included in the study and finally, 56 patients completed the study according to the protocol, including 47 (84%) females. The data comparison at baseline did not show any significant difference between the two groups except in the number of patients using valproic acid as prophylaxis (21 patients in the EPA group, and 13 in the placebo group; p = 0.037). The results showed after 8 weeks, a mean (SD) difference of Headache Impact Test-6 in the EPA and placebo groups was -6.96 (3.34) and -4.43 (5.24), respectively (p = 0.084). Regarding migraine headache days, participants reported a mean (SD) -9.76 (4.15) and -4.60 (4.87) decline in days with headache, respectively (p < 0.001). The number of attacks per month after 8 weeks was 3.0 (95% confidence interval [CI] 2.0-4.0) and 4.0 (95% CI 3.0-6.0), respectively (p < 0.001). Regarding severity, there was no significant difference between the two groups (mean [SD] difference: -0.76 [1.13] and -0.73 [1.04], respectively; p = 0.906). In terms of adverse events, two patients in the EPA group reported intolerable nausea and vomiting, and one patient in the placebo group reported dizziness. This study's findings support the potential of a daily 2000 mg EPA as a prophylactic pharmacotherapy in chronic migraine management, specifically in mitigating migraine attacks, migraine headache days, and overall quality of life.

Effects of fremanezumab on migraine-associated symptoms and medication use in Japanese and Korean patients with episodic migraine: Exploratory endpoint analysis of a multicenter, randomized, double-blind, placebo-controlled trial.

To describe exploratory endpoints from a previous phase 2b/3 placebo-controlled trial conducted in Japan and Korea, specifically investigating the effect of fremanezumab or placebo on migraine-associated symptoms and acute headache medication use in patients with episodic migraine (EM). EM is associated with non-head pain symptoms, including nausea, vomiting, photophobia, or phonophobia, which contribute substantially to the disease burden, healthcare resource utilization, and impaired quality of life. Current EM treatments include a mix of nonspecific/migraine-specific acute headache medications, but medication overuse can induce headaches and progression from EM to chronic migraine (CM). In multiple phase 2b/3 trials, the monoclonal antibody fremanezumab significantly reduced the average number of monthly migraine days experienced by patients with EM/CM compared with placebo. This was a prespecified analysis of exploratory endpoints in a multicenter, randomized, double-blind, placebo-controlled, phase 2b/3 trial conducted in Japanese and Korean patients with EM (NCT03303092). Patients were randomized to receive fremanezumab, either monthly or quarterly, or matching placebo, administered subcutaneously at 4-week/28-day ("monthly") intervals to maintain blinding. Exploratory endpoints reported here were the mean change from baseline in the number of days/month with (i) the use of any acute headache medication, (ii) the use of any migraine-specific acute headache medication, (iii) nausea or vomiting, and (iv) photophobia and phonophobia. Overall, 357 Japanese and Korean patients with EM received either monthly (n = 121) or quarterly (n = 119) fremanezumab or placebo (n = 117). Compared with placebo, fremanezumab administered monthly or quarterly was associated with a significant reduction from baseline in the average number of days/month with acute headache medication use over three months (difference vs. placebo -2.81 [95% confidence interval (CI) -3.52, -2.11]; p < 0.001 and -2.79 [95% CI -3.50, -2.08]; p < 0.001, respectively). Similar findings were observed in the monthly average number of days with migraine-specific acute headache medications (difference vs. placebo with monthly and quarterly fremanezumab, -2.63 [95% CI -3.31, -1.95] for both; p < 0.001), the average number of days/month with nausea or vomiting (difference vs. placebo -1.09 [95% CI -1.60, -0.58]; p < 0.001 for monthly fremanezumab and -1.37 [95% CI -1.88, -0.86]; p < 0.001 for quarterly fremanezumab), and the average number of days with photophobia and phonophobia (difference vs. placebo -1.22 [95% CI -1.80, -0.65]; p < 0.001 and -1.64 [95% CI -2.22, -1.06]; p < 0.001, respectively). Monthly and quarterly administered fremanezumab effectively prevented EM in Japanese and Korean patients. Fremanezumab also improved other disease aspects including the need for acute headache medications and the frequency of migraine-associated symptoms.

Symptoms across the phases of the migraine cycle from the patient's perspective: Results of the MiCOAS qualitative study.

To better understand the breadth and frequency of symptoms across the phases of the migraine cycle using data captured from qualitative patient interviews conducted through the Migraine Clinical Outcome Assessment System (MiCOAS) project. People living with migraine experience a range of symptoms across the pre-headache, headache, post-headache, and interictal phases of the migraine cycle. Although clinical diagnostic criteria and clinical trial endpoints focus largely on cardinal symptoms or monthly migraine days, migraine symptom profiles are far more complex. As a part of the MiCOAS project, semi-structured qualitative interviews were undertaken to better understand the migraine-related symptomology from the patient's viewpoint. This concept elicitation study used iterative purposeful sampling to select 40 people with self-reported medical diagnosis of migraine for interviews that were conducted via audio-only web conferencing. Key topics related to migraine symptoms, including mood/emotion symptoms, were identified using content analysis. Interview transcripts were also coded to reflect the phase of migraine under discussion, so that patient experiences could be compared by phase. Forty participants (50%, n = 20 episodic migraine; 50%, n = 20 chronic migraine), aged from 21 to 70 years old reported a total of 60 unique symptoms, which were categorized into 30 broader symptom categories. Participants reported between 7 and 22 unique symptom categories across all phases. During pre-headache and headache, participants reported a median of 7.5 (interquartile range [IQR] = 5.5) and 8 (IQR = 4.0) different symptom categories compared to 4 (IQR = 3.0) and 1.5 (IQR = 2.5) for the post-headache and interictal periods, respectively. Head pain during the headache phase was the only universally reported symptom (100%, n = 40). Pooling across all phases, the next most reported symptoms were light sensitivity (93%, n = 37), nausea (88%, n = 35), irritability/impatience (83%, n = 24), sound sensitivity (80%, n = 32), and fatigue/exhaustion (80%, n = 32). One or more interictal symptoms were reported by 73% (n = 29) of participants and included mood/emotion symptoms, such as anxiety (30%, n = 12), depression (18%, n = 7), and anger (15%, n = 6), as well as cardinal symptoms, such as light sensitivity (13%, n = 5) and nausea (13%, n = 5). Patients experience a range of symptoms across the phases of the migraine cycle. Results often aligned with clinical expectations, but non-cardinal migraine-related symptoms were reported both inside and outside the headache phase, including between attacks. These discoveries highlight the importance of assessing a range of symptoms and timing when developing patient-reported outcome measures for migraine clinical trials.