Search Results (118)

Background and Objectives: Greater occipital nerve pulsed radiofrequency (GON-PRF) is an effective neuromodulatory treatment for migraine; however, evidence directly comparing unilateral and bilateral approaches remains limited. This prospective randomized controlled trial compared the clinical efficacy of ultrasound-guided proximal GON-PRF performed unilaterally versus bilaterally at the C2 level in patients with migraine. Materials and Methods: A total of 187 patients were randomized to receive unilateral (n = 91) or bilateral (n = 96) ultrasound-guided proximal GON-PRF without concomitant local anesthetic or corticosteroids. Per-protocol analyses included 78 and 88 participants in the unilateral and bilateral groups, respectively. The primary outcome was the change in monthly headache days (MHD) from baseline to 6 months. Secondary outcomes included Visual Analog Scale (VAS) scores, acute medication days (AMD), Headache Impact Test-6 (HIT-6) scores, Migraine Disability Assessment (MIDAS) grades, and Global Perceived Effect (GPE) scores. Longitudinal outcomes were analyzed using multivariable Generalized Estimating Equations (GEE). Results: Of the 187 randomized participants, 166 completed the 6-month follow-up and were included in the per-protocol analysis. Both groups demonstrated significant improvements in all outcomes throughout follow-up (all p < 0.001). At month 6, the Bilateral Group showed lower MHD values (median [IQR]: 7.0 [6.0] vs. 10.0 [6.0], p = 0.030), a higher ≥50% MHD responder rate (77.3% vs. 55.1%, p = 0.003), and lower AMD values (p = 0.024). Adjusted GEE analyses demonstrated significant treatment effects favoring the Bilateral Group for average VAS (p = 0.047) and HIT-6 (p = 0.004). GPE scores also favored the Bilateral Group at month 6 (p = 0.044). No procedure-related complications occurred. Conclusions: Both unilateral and bilateral ultrasound-guided proximal GON-PRF provided significant clinical improvement in patients with migraine. However, bilateral treatment demonstrated superior longitudinal outcomes, including lower headache frequency, reduced acute medication use, higher ≥50% MHD responder rates, and greater patient-reported improvement. These findings remained consistent after adjustment for baseline covariates. Full article

Background: A substantial proportion of patients with chronic migraine (CM) with previous failures among oral standard-of-care migraine medications do not respond to monoclonal antibodies targeting the calcitonine gene related peptide pathway (CGRP-mAbs), leaving limited evidence-based options for subsequent preventive strategies. The present multicentre real-world study evaluated the effectiveness of onabotulinumtoxin-A (BoNT-A) in CM patients with previous CGRP-mAb failure and multiple prior oral preventive failures. Methods: This prospective, observational, non-randomized multicentre study enrolled patients with CM who had failed ≥3 classes of oral preventive treatments and ≥1 CGRP-mAb due to lack of efficacy or intolerance. Participants received BoNT-A according to the PREEMPT “follow-the-pain” paradigm every three months and were followed for 6 months. Co-primary outcomes were change in monthly headache days (MHD) after three and six months and ≥50% MHD responder rates at both time points. Results: Fifty-three patients were analysed (85% female, aged 48.5 ± 15.2 years, range 20–73). Compared to the baseline, at the third month and sixth month, MHD decreased from 22.83 (SD 6.74) to 15.38 (SD 7.91; p < 0.001) and 14.55 (SD 9.35; p < 0.001), respectively. The percentages of participants achieving the response status in MMD at the third month and sixth month were 30% and 45%, respectively. In the third and sixth months, 22 patients (41.5%) and 27 patients (50.9%), respectively, converted from chronic to episodic migraine, while the prevalence of medication-overuse headache decreased from 81.1% of patients at baseline to 45.3% and 43.4%, respectively. Migraine-related impact and disability scores improved over follow-up, alongside improvements in anxiety and depressive symptoms and in migraine-specific quality of life. Conclusions: The present findings support the use of BoNT-A in difficult-to-treat patients with CM following CGRP-mAb failure and provide further evidence that its therapeutic effects may rely on mechanisms that are at least partially distinct from, and potentially complementary to, those of CGRP-targeted therapies. Full article

Background: Migraine is a disabling neurological disorder in which neuropeptides, particularly pituitary adenylate cyclase-activating polypeptide (PACAP), play pathogenic roles. The kynurenine pathway (KP) is increasingly implicated in migraine-related glutamatergic and neuroinflammatory mechanisms. Previously, we showed that the neuroprotective metabolite kynurenic acid attenuates PACAP overexpression following trigeminovascular activation. This study investigated the effects of kynurenine aminotransferase II (KAT-II) inhibition on PACAP expression and KP metabolites during trigeminal sensitization. Methods: Rats received Complete Freund’s Adjuvant (CFA) or saline injection into the right whisker pad. KAT-II inhibitor PF-04859989 (16 and 32 mg/kg) or saline was administered intraperitoneally 72 h later. Blood samples and nucleus trigeminus caudalis (TNC) were collected for PACAP and KP quantification. Results: CFA treatment induced significant PACAP overexpression in the TNC and altered peripheral KP metabolite levels. PF-04859989 further increased PACAP expression, reaching significance at the 16 mg/kg dose, whereas no significant additional effect was observed at 32 mg/kg. In parallel, treatment with PF-04859989 altered peripheral KP metabolite concentrations in the peripheral inflammatory model, predominantly at the lower dose. Conclusions: This study demonstrates that KAT-II inhibition by PF-04859989 modulates PACAP signaling and KP metabolism under trigeminal inflammatory conditions. These findings support KP–PACAP interactions and may identify novel migraine-related therapeutic targets. Full article

Background/Objectives: Chronic migraine is a disabling neurological disorder that significantly impairs quality of life. Interventional procedures, including greater occipital nerve (GON) block and sphenopalatine ganglion (SPG) block, are increasingly used as adjuncts to standard pharmacological treatment. The aim of this study was to compare the effectiveness of GON and SPG blocks in patients with chronic migraine. Methods: This retrospective observational study included 50 patients diagnosed with chronic migraine according to the International Classification of Headache Disorders, 3rd edition (ICHD-3). Patients were assigned to either a GON block group or an SPG block group. Monthly migraine days, pain intensity measured using the Visual Analog Scale (VAS), and migraine-related disability assessed with the Headache Impact Test-6 (HIT-6) and Migraine Disability Assessment (MIDAS) questionnaires were evaluated before treatment and after completion of two procedures. Results: Both GON and SPG blocks were associated with significant reductions in monthly migraine days, pain intensity, and disability scores. A greater reduction in monthly migraine days was observed in patients treated with GON block compared with those treated with SPG block. Conclusions: Both GON and SPG blocks may represent effective adjunctive treatment options for patients with chronic migraine. In this study, GON block was associated with a greater reduction in migraine frequency, although further prospective studies are needed to confirm these findings. Full article

Background: Monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway represent an effective preventive treatment for chronic migraine, including in patients with multiple prior therapeutic failures. However, a substantial proportion of patients exhibit a suboptimal or delayed response. The role of personality traits in modulating treatment response remains poorly understood. Methods: In this prospective observational study, adults with chronic migraine received anti-CGRP monoclonal antibodies and were followed for 12 months. Monthly headache days (MHDs), monthly acute medication use (MAM), and disability scores (MIDAS and HIT-6) were recorded at baseline and at 3, 6, and 12 months. Responders were defined as patients achieving a ≥50% reduction in monthly headache days (MHDs) compared with baseline. Changes in disability measures were evaluated as secondary clinical outcomes. Personality traits were assessed using the Millon Clinical Multiaxial Inventory-III. Results: Thirty-eight patients were included, of whom 71% had medication overuse headaches. Responder rates increased over time (31.6% at 3 months and 39.5% at 12 months). Histrionic traits (37.5% vs. 6.7%, p = 0.048) and dysthymic features (21.4% vs. 0%, p = 0.046) were significantly more prevalent among non-responders. Conclusions: Histrionic and dysthymic personality features were associated with a lower likelihood of response to anti-CGRP therapy in patients with chronic migraine. Given the exploratory design, limited sample size, and absence of correction for multiple comparisons, these findings should be considered preliminary and hypothesis-generating. Further studies in larger cohorts are needed to confirm these observations. Full article

Background/Objectives: Migraine is common in women and is associated with significant disability and reduced quality of life. Type D personality, characterized by negative affectivity and social inhibition, has been linked to poorer outcomes in chronic illnesses; however, its association with migraine-related impact and functioning in women has not been fully clarified. This study examined the associations of Type D personality with headache impact and overall functioning in women with migraine, with an exploratory focus on the indirect statistical associations involving psychological symptoms, pain severity, and age. Methods: In this cross-sectional study, 204 women with migraine were assessed. Type D personality was measured using the DS14, headache impact using the HIT-6, and functioning using the FAST. Anxiety and depression were measured with the HADS, and pain severity with a visual analog scale. Analyses included group comparisons, correlations, exploratory mediation analyses, and moderation analyses. Results: Type D personality was present in 41.2% of participants. Women with Type D personality had more chronic migraine, physical comorbidities, lower education and employment, and greater functional impairment. Type D personality was correlated with headache impact, functional impairment, anxiety, and depression. Anxiety and pain severity showed significant indirect statistical associations in the relationship between Type D personality and headache impact, while depression showed a significant indirect statistical association in the relationship between Type D personality and functioning. Age moderated the association between Type D personality and headache impact, with a stronger association observed in older women. Conclusions: In women with migraine, Type D personality was associated with greater functional impairment, whereas its association with headache impact was attenuated after adjustment for relevant clinical and psychological factors. Psychological symptoms and pain severity showed significant indirect statistical associations with migraine-related outcomes; however, causal inferences cannot be drawn due to the cross-sectional design. These findings highlight the potential clinical relevance of assessing personality traits and psychological symptoms in women with migraine. Full article

Background/Objectives: Migraine is a common neurovascular disorder associated with substantial disability. Increasing evidence suggests that hypoxia-related signaling, endothelial dysfunction, and nitric oxide metabolism contribute to its pathophysiology. This study investigated the relationships between hypoxia-inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor A (VEGF-A), and arginine pathway metabolites in chronic migraine. Methods: In this observational study, fasting ethylenediaminetetraacetic acid (EDTA) plasma samples were obtained from 28 patients with chronic migraine and 28 healthy controls. Arginine, citrulline, and ornithine concentrations were quantified by liquid chromatography–tandem mass spectrometry, whereas HIF-1α and VEGF-A were measured using enzyme-linked immunosorbent assays. Group comparisons, receiver operating characteristic analyses, and Firth penalized logistic regression models were performed. Results: Patients with chronic migraine exhibited significantly higher VEGF-A and HIF-1α concentrations than controls (both FDR-adjusted p ≤ 0.001). VEGF-A demonstrated excellent discrimination of migraine status (AUC = 0.973), whereas HIF-1α showed good discriminatory performance (AUC = 0.794). The arginine-to-citrulline ratio was higher (FDR-adjusted p = 0.032) and ornithine concentrations were lower (FDR-adjusted p = 0.043) in migraine patients. In multivariable analyses, VEGF-A (OR = 14.46), HIF-1α (OR = 5.83), and ornithine (OR = 0.28) remained independently associated with migraine status. Conclusions: Chronic migraine was associated with elevated circulating HIF-1α and VEGF-A concentrations together with alterations in arginine metabolism. These exploratory findings suggest that hypoxia-responsive signaling, endothelial activation, and nitric oxide-related metabolic pathways may represent interconnected biological processes associated with chronic migraine. Larger longitudinal and externally validated studies are required to confirm these observations and clarify their potential clinical relevance. Full article

Background/Objectives: This study aimed to examine the associations between diet-related quality of life (DRQOL) and psychological distress, autonomic dysfunction, and migraine in patients with dizziness and balance disorders. Methods: In this retrospective cross-sectional study, 122 patients (56 men, 66 women; mean age 40.4 ± 12.8 years, minimum 14, maximum 65) from the vertigo outpatient clinic at JR Tokyo General Hospital completed self-reported questionnaires. These included the DRQOL scale, Dizziness Handicap Inventory (DHI), Hospital Anxiety and Depression Scale (HADS), Self-rating Depression Scale (SDS), Orthostatic Dysregulation (OD) checklist, and migraine assessments (POUNDing [Pulsating, duration of 4–72 h, Unilateral, Nausea, Disabling], MIDAS, migraine screener). Correlational analyses, group comparisons, and receiver operating characteristic (ROC) analyses were conducted. Results: Higher DRQOL scores indicate poorer DRQOL. DRQOL scores showed positive correlations with psychological distress (SDS: ρ = 0.57; HADS-A: ρ = 0.50; HADS-D: ρ = 0.53; all p < 0.001) and OD severity (ρ = 0.50, p < 0.001) but not with age, DHI, or individual migraine indices. Migraine screener-positive patients had significantly higher DRQOL scores (p < 0.01). DRQOL alone showed modest ability to discriminate migraine screener-positive from migraine screener-negative patients (AUC = 0.65); discrimination improved to an AUC of 0.77 in a multivariable model that also included age and sex. Conclusions: DRQOL appears to capture psychological and autonomic symptom burden rather than vestibular or headache severity, suggesting that it may serve as a complementary, patient-centered metric that adds a multidimensional perspective to conventional vestibular and headache assessments. Full article

Background/Objective: Medication overuse headache (MOH) is a disabling secondary headache disorder that arises from an underlying primary headache, most commonly migraine. Although treatment reduces headache frequency and medication overuse, the interictal burden—the impact experienced between headache attacks—remains poorly characterized over the long term. This study evaluated interictal burden and clinical outcomes two years after MOH diagnosis. Methods: This study was derived from a prospective multicenter cohort of patients with MOH, using data from a single center. Of 149 patients enrolled between April 2020 and November 2022, 117 (78.5%) completed the two-year follow-up. Clinical characteristics, medication overuse, monthly headache days, and standardized questionnaires were assessed at baseline and follow-up. Interictal burden was evaluated at two years using the Migraine Interictal Burden Scale (MIBS-4), with scores ≥5 indicating severe burden. Results: At baseline, patients (81.2% female; median age, 45.0 years) reported a median of 16.0 monthly medication days (interquartile range, 13.0–23.0). Medication overuse decreased from 100% at baseline to 24.2% at one year and 17.1% at two years. Among 117 patients with available two-year MIBS-4 data, 25 (21.4%) had severe interictal burden. Compared with those without severe burden, these patients had greater headache-related impact and disability (HIT-6: 68.0 vs. 64.0, p = 0.019; MIDAS: 110.0 vs. 36.0, p = 0.002), higher psychological burden (PHQ-9: 11.0 vs. 8.0, p = 0.032; GAD-7: 7.0 vs. 4.0, p = 0.010), and were more likely to be current smokers (20.0% vs. 4.3%, p = 0.036). Notably, 14.4% of patients with resolved medication overuse still reported severe interictal burden. Conclusions: Two years after MOH diagnosis, severe interictal burden was observed in a substantial proportion of patients and was associated with greater baseline disability and psychological distress. These findings highlight the need for long-term monitoring and management beyond initial medication withdrawal. Full article

Background: Migraine (MIG) management guidelines support a comprehensive approach combining medication, therapeutic patient education (TPE), behavioral strategies, lifestyle changes, diet, and physical activity (PA). Objective: To present an innovative interdisciplinary outpatient model for individuals with MIG, focusing on PA, sedentary behavior, eating habits (EH), metabolic health, temporomandibular disorders, and postural dysfunctions. Design: A randomized controlled trial will enroll 200 adults with MIG over two years. Inclusion criteria are chronic MIG (≥15 attacks/month for ≥3 months) or high-frequency episodic MIG (8–14 attacks/month), physical inactivity, and independent walking ability. Exclusion criteria include contraindications to PA and lack of informed consent. Participants will be randomized to standard care (SC) or an intervention group receiving TPE plus three months of supervised exercise (EXE). All participants will receive an informational brochure with nutritional tips (included in SC) and undergo: (1) neurological examination, (2) validated questionnaires, (3) kinesiological and postural assessment, and (4) gnathological evaluation. The primary outcome is change in monthly MIG frequency at 6 and 12 months; additional outcomes include disability, quality of life, and intensity of MIG, PA levels, sedentary behavior, medication use, EH, functional capabilities, postural parameters, and temporomandibular disorder-related variables. Results: Hypothetically, the intervention may reduce monthly MIG frequency by approximately 15–20% relative to baseline. Improvements may also occur in disability, quality of life, medication use, lifestyle behaviors, and psychological and cardiometabolic parameters. Conclusions: This trial will evaluate whether adding supervised EXE and TPE to SC may improve MIG outcomes compared with SC alone, supporting a comprehensive management strategy. Full article

Background/Objectives: Migraine may be associated with structural changes in the brain, including the cerebellum and brainstem. Some of these changes reflect the brain’s plasticity in adapting to migraine-related alterations, but others may influence the severity of migraines and resistance to treatment. Some studies report changes in cortical thickness among migraine patients, and focal cortical dysplasia (FCD) has been considered a possible cause of these changes. We argued that FCD could contribute to the development of migraine and the severity of its symptoms. To date, there has been no consistent report of FCD occurring in migraine patients. Case: A 29-year-old woman presented with a history of at least 19 years of high-frequency episodic migraine without aura. She experienced motion sickness during childhood and adolescence. Her condition worsened last year, evolving into chronic migraine, which was partially controlled by medications such as amitriptyline and rizatriptan, leading to high-frequency episodic migraines. An MRI conducted in 2024 showed a small area of signal abnormality in the left occipital lobe, believed to represent cortical dysplasia. A follow-up MRI after three months showed no changes in this area. She is currently diagnosed with high-frequency episodic migraine and demonstrated severe migraine-related disability, with a MIDAS score of 25, and a severe impact on daily functioning, with a HIT-6 score of 65. Conclusions: The case involves a worsening migraine that was somewhat alleviated by a pharmacological intervention. FCD may contribute to brain hyperexcitability in this case and her motion-related problems during childhood and adolescence. FCD could also play a role in the increasing severity of her migraines and her partial resistance to medication. Full article

Background: Migraine is frequently associated with anxiety, depression, and reduced quality of life, contributing to substantial functional impairment. Objective: To examine longitudinal changes in affective symptoms, headache-related burden, and quality of life following repetitive transcranial magnetic stimulation (rTMS) in individuals with migraine. Methods: In this one-arm longitudinal study, 32 adults with migraine underwent 10 sessions of rTMS. Anxiety (HAMA), depression (HAMD), and migraine-specific quality of life were assessed at baseline, post-treatment, and 3-month follow-up, while headache impact (HIT-6) and disability (MIDAS) were evaluated at baseline and post-treatment. Repeated-measures analyses and paired comparisons were conducted. Results: Significant improvements over time were observed for anxiety, depression, and quality of life (all p < 0.001). Anxiety showed progressive improvement through follow-up, while depressive symptoms improved early with further consolidation at 3 months. Migraine-related quality of life increased significantly across all timepoints. Headache impact and disability decreased significantly following treatment (both p < 0.001), with large effect sizes. Conclusions: rTMS was associated with improvements in affective symptoms, migraine-related burden, and quality of life. However, given the one-arm design, these findings should be interpreted cautiously. Controlled studies are needed to confirm these results. Full article

Background: Migraine in older adults represents an increasingly relevant yet underrecognized clinical challenge in aging societies, where multimorbidity, frailty, and polypharmacy complicate both diagnosis and management. Although traditionally considered a disorder of younger individuals, migraine frequently persists or presents after the age of 60 with atypical features, contributing to diagnostic uncertainty. Methods: This narrative review, conducted in accordance with the SANRA principles, aims to provide a comprehensive overview of the epidemiology, clinical presentation, pathophysiology, and management of migraine in older adults, with particular emphasis on age-related complexities, therapeutic challenges, and unmet clinical needs. Results: Migraine in this population often presents with atypical or misleading features, such as aura without headache, vestibular symptoms, or overlap with cerebrovascular conditions, leading to delayed or incorrect diagnoses. The burden of disease is substantial, affecting physical function, mobility, cognition, emotional well-being, and social participation, and is further amplified by comorbid conditions including cardiovascular and metabolic disorders, mood disturbances, and chronic pain syndromes. Aging-related neurobiological changes, such as impaired pain modulation, endothelial dysfunction, and neuroinflammation, may influence disease expression and treatment response. Therapeutic management is challenged by contraindications, increased susceptibility to adverse drug effects, and the complexity of polypharmacy, highlighting the importance of individualized and non-pharmacological approaches. Conclusions: Migraine in older adults is a significant but often overlooked contributor to disability and reduced quality of life. Improved recognition of its unique clinical features and age-specific vulnerabilities is essential to optimize patient-centered care. Future research should prioritize the inclusion of older populations and the development of tailored, safe, and effective management strategies. Full article

Background: Migraine is a chronic neurological disorder with a high prevalence of psychiatric comorbidity, including anxiety and depression, which compound functional impairment and reduce health-related quality of life (HRQoL). Repetitive transcranial magnetic stimulation (rTMS) is a non-pharmacological neuromodulatory intervention targeting both pain and affective circuits; however, predictors of HRQoL improvement following rTMS remain poorly characterized. Methods: In this exploratory observational study, 32 adults with migraines underwent 10–40 rTMS sessions. Quality of life was assessed using the WHOQOL-BREF and Migraine-Specific Quality of Life Questionnaire (Migraine-QoL). Psychiatric burden, headache impact, and disability were evaluated using HAMA, HAMD, HIT-6, and MIDAS at baseline and post-intervention. Paired t-tests, Spearman correlations, and linear regression identified predictors of QoL change. Results: Both WHOQOL-BREF and Migraine-QoL improved significantly following rTMS (p < 0.001). Antipsychotic use was associated with greater overall QoL improvement (p = 0.026). Given the very small subgroup size (n = 7), this finding should be interpreted with extreme caution and considered hypothesis-generating only. Higher baseline HIT-6 and HAMA correlated with greater Migraine-QoL gains (p = 0.001 and p = 0.013). In multivariate regression, higher headache severity independently predicted Migraine-QoL improvement (R² = 0.514, p < 0.001). Conclusions: rTMS produced clinically meaningful QoL improvements in migraine. Headache burden emerged as an independent predictor, while associations with anxiety severity and antipsychotic use should be considered exploratory. Full article

Background: Sleep disturbance is a well-recognized contributor to headache burden, yet the specific sleep domains associated with disability may differ between episodic migraine (EM) and episodic cluster headache (ECH). Methods: In this prospective observational study, 20 EM patients, 21 ECH patients, and 18 age-, sex-, and BMI-matched healthy controls (HCs) were evaluated during interictal periods. None of the patients were receiving prophylactic headache treatment. Sleep was assessed using the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), and Sleep Hygiene Index (SHI). Psychological status was measured with the Hospital Anxiety and Depression Scale (HADS). Headache-related disability was assessed using the Headache Impact Test-6 (HIT-6) as a continuous outcome. Separate multivariable linear regression models were constructed for each headache group. Results: Both headache groups showed significantly impaired sleep and higher anxiety and depression scores compared with controls (all p < 0.001). HIT-6 scores did not differ between EM and ECH (p = 0.770 after Bonferroni correction). In multivariable regression, excessive daytime sleepiness (ESS) independently predicted disability in EM (B = 1.633, p = 0.033; R² = 0.571). In ECH, global sleep quality (PSQI; B = 0.701, p = 0.004) and sleep hygiene (SHI; B = 0.557, p = 0.033) were independently associated with HIT-6 (R² = 0.562). No significant multicollinearity was observed (all VIF < 2.5). Conclusions: Sleep disturbance is prevalent in both EM and ECH; however, the sleep domains associated with disability differ between phenotypes. Daytime sleepiness is more relevant in EM, whereas global sleep quality and sleep hygiene are more strongly associated with disability in ECH. These findings support a phenotype-specific approach to sleep assessment in headache management. Full article