Search Results (654)

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 and Objectives: Migraine is a chronic, throbbing type of headache that affects large populations worldwide. This condition is associated with neuroinflammation. Materials and Methods: In this study, polymorphism analyses were performed by KASP PCR. Serum interleukin-6 (IL-6) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels were measured using kits based on the enzyme-linked immunosorbent assay (ELISA) principle. Results: In the APE1 Asp148Glu (rs1130409) gene polymorphism analysis, the frequency of the mutant G (Glu) allele was 93.1% and 48.0% in the control and migraine populations, respectively, while the frequency of the wild-type T (Asp) allele was 6.9% and 52.0% (p < 0.001). The frequency of the T/T (Asp/Asp) genotype was high in the migraine group (p < 0.001), while the frequency of the G/G (Glu/Glu) genotype was higher in the control group at 86.2%, compared to the migraine group (p < 0.001). The total frequency of the T/G+ G/G (Asp/Glu+Glu/Glu) composite genotype was determined to be 65.9% in the control group and 34.1% in the migraine group (p < 0.001). There was no statistical difference in allele and genotype frequency between the control and migraine groups for the XRCC1 Arg399Gln (rs25487) gene polymorphism. Serum 8-OHdG and IL-6 levels were comparable between the groups, with no statistically significant differences observed. Conclusions: Future studies with larger and more homogeneous populations are needed to further elucidate the potential interactions between inflammatory processes and DNA damage in migraine. Consideration of attack duration and environmental exposures may improve interpretation of biomarker variability. Expanding the analysis to additional DNA repair gene polymorphisms may also contribute to a better understanding of the molecular background of migraine and the evaluation of potential biomarkers. Full article

The role of the catechol-O-methyltransferase (COMT) Val158Met rs4680 polymorphism in altered pain processing in headaches is controversial. The aim of this study was to investigate the influence of the Val158Met rs4680 polymorphism in conditioned pain modulation (CPM) in women with migraine. A case-control study including 70 women with chronic migraine, 70 with episodic migraine and 70 pain-free women was conducted. Pressure pain thresholds (PPTs) at the temporalis muscle, lateral epicondyle, and tibialis anterior were bilaterally assessed. Heat (HPT) and cold (CPT) pain thresholds at the frontalis muscle were also assessed. Subsequently, CPM was evaluated immediately after a one-minute cold-pressor test paradigm on changes obtained in PPTs, HPT and CPT. Thus, after amplifying Val158Met polymorphism by polymerase chain reaction, genotype frequencies (Val/Val, Val/Met, or Met/Met) and allele distributions were identified. The distribution of Val158Met genotypes (p = 0.097) was not significantly different among women with episodic migraine, chronic migraine and pain-free controls. The results revealed significant group*time*Val 158Met interactions for PPTs at the temporalis (Wilk’s λ = 0.917, F [4, 193] = 4.377, p = 0.002, n²p = 0.083, 1 − β = 0.930) and lateral epicondyle (Wilk’s λ = 0.892, F [4, 193] = 5.870, p < 0.001, n²p = 0.108, 1 − β = 0.982), as well as CPT (Wilk’s λ = 0.872, F [4, 193] = 7.111, p < 0.001, n²p = 0.128, 1 − β = 0.995) or HPT (Wilk’s λ = 0.921, F [4, 193] = 4.133, p = 0.003, n²p = 0.079, β − 1 = 0.914), but not for the PPT at tibialis anterior (Wilk’s λ = 0.983, F [4, 193] = 0.834, p = 0.505, n²p = 0.017, 1 − β = 0.263). Women with chronic migraine with the Met/Met genotype exhibited reduced CPM indexes for PPT, CPT, or HPT at the temporalis (trigeminal area) than those with the Val/Val genotype. This study showed that CPM deficit is higher in women with migraine with the Met/Met genotype, but this association is mostly present in the symptomatic (trigeminal) area in the chronic form of the disease. No association of the Met/Met genotype with CPM was seen in healthy controls. Full article

Background/Objectives: The aim of this pilot study was to evaluate the feasibility of developing individualized machine learning models using nocturnal wearable-derived autonomic nervous system (ANS) and sleep metrics to predict next-day headache risk in patients with migraine. We also examined the associations between nocturnal ANS and sleep measures and patient-reported outcome measures (PROMs) related to nociplastic pain, migraine burden, and non-restorative sleep (NRS). Methods: Adults with migraine wore the wrist-worn Empatica EmbracePlus^® wearable during sleep and completed daily headache diaries for approximately 4 weeks (N = 10). Participants also completed daily headache diaries and PROMs assessing nociplastic pain, migraine burden, and non-restorative sleep. Personalized machine learning (ML) models were developed to predict next-day headache using nocturnal ANS activity (e.g., pulse rate variability (PRV), electrodermal activity (EDA), respiratory rate (RR)) and sleep metrics (e.g., interruptions, duration, awakenings). Model performance was evaluated using area under the receiver operating characteristic and precision–recall curves (AUROC, AUPRC), sensitivity, specificity, accuracy, and precision. Spearman correlations assessed the relationship between wearable-derived metrics and patient-reported outcome measurements of sleep quality (PROMIS-Fatigue, PROMIS-Sleep Disturbance) and a surrogate marker of nociplastic pain (Fibromyalgia (FM) Score). Results: 9 out of 10 participants wore the EmbracePlus device for at least the target duration of four weeks. For the next-day headache prediction, model performance varied between individuals; area under the ROC curve (AUROC) ranged from 28.2% to 81.2%. Nocturnal measures of EDA were strongly correlated with the FM score (Spearman’s rho = 0.72–0.75, p < 0.05). Conclusions: Phasic EDA may warrant further investigation as a potential physiological indicator related to nociplastic pain mechanisms and next-day headache. However, these findings are preliminary, and larger multicenter trials are needed to confirm results of this pilot study. Full article

Background/Objectives: Migraine and Hashimoto’s thyroiditis (HT) are frequently comorbid, implying shared biological pathways. Selenium and myoinositol are involved in migraine pathophysiology, and their supplementation has been shown to improve thyroid function, particularly in individuals with HT. This study aimed to evaluate the impact of combined myoinositol and selenium (MYSE) supplementation on thyroid function and migraine outcomes in patients with migraine and HT. Methods: We conducted a retrospective study on a cohort of 163 adults with migraine comorbid with HT who received a 6-month MYSE supplementation. Thyroid parameters, namely thyrotropin (TSH), free thyroxine (fT4), and free triiodothyronine (fT3), and migraine features, namely monthly migraine days (MMDs), monthly migraine attacks (MMAs), and monthly symptomatic drug use (MSDs), were assessed at baseline and at follow-up. Because Shapiro–Wilk testing showed that all thyroid and migraine outcomes deviated significantly from normality, pre–post comparisons were evaluated with the Wilcoxon signed-rank test, between-group comparisons with the Mann–Whitney U test, and a three-tier non-parametric strategy (Aligned Rank Transform with ART-C contrasts, the Brunner–Langer non-parametric mixed model, and a trimmed-means between-within ANOVA) to analyze time × migraine × gender, adjusted for age and illness duration. Spearman rank correlations with percentile-bootstrap 95% confidence intervals were computed, and both robust MM-regression and rank-based Jaeckel regression were carried out. Another analysis stratified participants by baseline thyroid status: euthyroid vs. subclinical hypothyroidism (SCH). Results: After six months of MYSE supplementation, significant reductions were observed in TSH (median 3.60 → 2.80 mIU/L, Wilcoxon p < 0.001, rank-biserial r = −0.94), MMDs (14 → 11, p < 0.001, r = −0.99), and MSDs (14 → 11, p < 0.001, r = −0.99), while fT4 increased slightly (1.30 → 1.50 ng/dL, p < 0.001) and fT3 remained stable. For MMAs, a small effect was detected by the paired Wilcoxon test (p = 0.002) but the main effect of time did not survive adjustment in any of the three covariate-adjusted mixed models (ART p = 0.079; nparLD p = 0.55; WRS2 p = 0.084). Chronic migraine patients had higher baseline and follow-up headache burden but experienced greater reductions in MMDs. The percentage reduction in TSH was positively correlated with improvement in MMDs (Spearman ρ = 0.45, bootstrap 95% CI 0.31–0.57, p < 0.001) and was the only significant predictor in both robust MM-regression (β = 0.28, p < 0.001) and rank-based regression (β = 0.25, p < 0.001). The TSH–MMD association held within each thyroid-status stratum separately (ρ = 0.42 in euthyroid, ρ = 0.51 in SCH; p < 0.001 for both), indicating an individual-level signal rather than a between-group artefact. Conclusions: MYSE supplementation was associated with improved thyroid parameters and a meaningful reduction in migraine burden among patients with migraine and HT. The association between TSH reduction and headache improvement supports the hypothesis of an endocrine–metabolic contribution to migraine severity and warrants confirmation in prospective controlled trials. It also supports the clinical value of assessing and addressing thyroid function in this population. 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: Headache is a frequent but often underestimated complaint in patients with sarcoidosis. In clinical practice, headache is commonly interpreted as secondary to neurosarcoidosis, potentially overlooking the presence of primary headache disorders, particularly migraine. The prevalence and clinical relevance of migraine in sarcoidosis remain insufficiently characterized. Objective: To investigate the prevalence and clinical characteristics of migraine in patients with sarcoidosis and to explore its association with pulmonary functional outcomes. Methods: The OUtcome and Clinical characteristics of primary Headache in patients with Sarcoidosis (OUCH!) Study is a multicenter, retrospective, observational study including adult patients evaluated at pulmonology outpatient clinics and headache centers between January 2019 and January 2021. Demographic, clinical, radiological, and pulmonary function data were collected. Patients were stratified according to the presence or absence of migraine. Pulmonary function parameters were compared using non-parametric statistical tests. Results: Seventy-two patients with sarcoidosis were included; 21 (29.2%) were diagnosed with migraine. Migraine prevalence was higher than expected for the general population. Pulmonary involvement was the most frequent disease manifestation. Patients with migraine showed significantly lower DLCO values compared with those without migraine (median (IQR): 55 (40–70) vs. 78 (65–90); p = 0.0009). No significant differences were observed in spirometric parameters or radiological patterns between groups. Conclusions: Migraine is a common comorbidity in sarcoidosis and is associated with reduced DLCO, suggesting a link with greater functional disease burden rather than structural lung damage. Migraine should be recognized as a primary headache disorder in this population, rather than automatically attributed to neurosarcoidosis. These findings support a multidisciplinary, patient-centered approach and warrant prospective studies to clarify shared inflammatory, vascular, and neuroimmune mechanisms. Full article

Background and Clinical Significance: Migraine is a common yet debilitating condition that significantly impacts personal lives, productivity, and the healthcare system. Pharmacological interventions provide relief for some migraine sufferers, but for others, are ineffective or accompanied by side effects. Emerging evidence implicates autonomic nervous system dysfunction in migraine pathophysiology, suggesting that mind–body interventions may offer a simple, cost-free therapeutic option. Case Presentation: A 61-year-old woman presented with severe daily migraines that had persisted for years despite medication and dietary changes. Upon starting a regular 10 min slow diaphragmatic breathing practice, her migraines ceased immediately. At a 12-month follow-up, she had only experienced two minor headaches and reported improvements in both daily functioning and quality of life. Conclusions: These findings underscore the potential role of autonomic imbalance in chronic migraine and the preliminary feasibility of breathing interventions as an accessible, low-risk treatment that may, for some, surpass medication in efficacy. Breathing practices may offer a viable alternative to pharmaceutical interventions that benefits both patients and healthcare systems alike. Full article

Background: Migraine is a highly prevalent neurological disorder associated with substantial disability and socioeconomic burden. Although pharmacological therapies remain the mainstay of treatment, their effectiveness may be limited by incomplete response and adverse effects. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a non-invasive neuromodulatory technique that may modulate cortical excitability and pain-processing networks involved in migraine pathophysiology. This systematic review aimed to evaluate the current evidence regarding the efficacy and safety of rTMS compared with sham stimulation in individuals with migraine. Methods: A systematic search was conducted in PubMed (MEDLINE), PsycNet, and Ovid (including MEDLINE and Embase) from database inception to December 2025 in accordance with PRISMA 2020 guidelines. Studies investigating rTMS in adults with migraine and including a sham comparator were eligible for inclusion. Data regarding study design, participant characteristics, rTMS parameters, outcomes, and adverse events were extracted using a predefined template. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Results: Seven studies comprising a total of 301 participants were included. Most trials evaluated high-frequency rTMS targeting the dorsolateral prefrontal cortex. Across studies, rTMS was generally associated with reductions in migraine frequency and severity compared with sham stimulation, although results varied depending on stimulation parameters and study design. Treatment was consistently well tolerated, with only mild and transient adverse effects reported. However, considerable heterogeneity was observed in diagnostic criteria, stimulation protocols, outcome measures, and follow-up duration. Conclusions: Preliminary evidence suggests that rTMS may represent a promising and well-tolerated neuromodulatory approach for migraine management. Nevertheless, methodological variability, limited sample sizes, and concerns regarding risk of bias restrict definitive conclusions. Larger randomized controlled trials with standardized protocols and longer follow-up periods are needed to clarify the clinical role of rTMS in migraine treatment. Full article

Background/Objectives: Monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway are effective drugs for migraine prevention. The worsening of symptoms after treatment discontinuation has raised the question of whether these agents are associated with sustained central neurophysiological adaptation. This study investigated treatment-associated changes in sensory processing and cortical network efficiency during preventive treatment with CGRP monoclonal antibodies (mAbs). Methods: Twenty-two patients with episodic migraine (21 female, 46.2 ± 13.8 years) and 22 age- and sex-matched healthy controls underwent visual and somatosensory evoked-potential (VEP, SSEP) assessments and quantitative electroencephalography (qEEG). Patients were investigated before treatment initiation (V0) and after 3 months of CGRP mAb treatment (V3). Healthy controls were assessed once. Results: The lack of habituation of VEPs at V0 shifted toward habituation at V3 following treatment with CGRP mAbs (Δslope: −0.37 ± 0.83, p = 0.03). VEP habituation at V3 no longer differed significantly from controls. SSEP amplitudes remained stable and did not differ significantly between groups across the study interval. Exploratory qEEG parameters indicated a less efficient cortical network organization at V0 that was no longer significantly different from controls at V3. Conclusions: Three months of CGRP mAb treatment was associated with a partial normalization of selected neurophysiological parameters, particularly VEP habituation and exploratory qEEG network measures. Given the study design and small sample size, these findings indicate adaptive changes in multi-domain processing, yet these should not be overinterpreted as proof of disease modification. 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: Migraine is a chronic illness that may impact the daily living and quality of life of affected individuals and might lead to excessive use of antimigraine medications. Quality of life in migraine patients is crucial, as it highlights the significant impact of migraines on daily activities, emotional well-being, and overall health. This study aims to assess the association between medication overuse headache and migraine-specific quality of life in migraine patients. Methods: A cross-sectional study was conducted at a neurology clinic in Riyadh, Saudi Arabia, from April 2025 to October 2025. Data about the quality of life were collected using the Migraine-Specific Quality of Life Questionnaire (MSQ). Medication overuse was identified using the International Classification of Headache Disorders, third edition (ICHD-3) criteria, and migraine severity was classified using the Migraine Symptom Severity Scale. Descriptive statistics were used to describe the study sample. Bivariate tests and multivariable linear regression were used to assess factors associated with MSQ. All statistical analyses were performed using SAS (ver. 9.4). Results: A total of 152 migraine patients were included, of whom 17.1% met the criteria for medication overuse headache (MOH). In bivariate analyses, MOH was significantly associated with lower Migraine-Specific Quality of Life (MSQ) scores across all domains (p < 0.001). Multiple adjusted linear regression confirmed MOH and migraine severity as the factors independently associated with reduced MSQ, with MOH associated with lower RR (β = –11.65), RP (β = –12.84), and EF (β = –16.23) scores (all p < 0.05). Conclusions: Medication overuse headache is common among migraine patients, affecting nearly one in six individuals in this study. It is strongly associated with increased migraine severity and a substantial reduction in quality of life across all domains. These findings highlight the critical need for early identification and appropriate management of medication overuse in clinical practice. Full article

Background: Menstrual migraine (MM), including pure menstrual migraine (PMM) and menstrually related migraine (MRM), is characterized by attacks occurring in close temporal association with menstruation and is often more severe, longer lasting, and less responsive to treatment than non-menstrual migraine. Prostaglandin-mediated inflammation and calcitonin gene-related peptide (CGRP) release play a key role in MM pathophysiology. Phycocyanin (PC) and palmitoylethanolamide (PEA) are nutraceutical compounds with anti-inflammatory, analgesic, and neuroprotective properties that may be beneficial as short-term perimenstrual prophylaxis. Objectives: To evaluate the effectiveness of an oral supplementation combining phycocyanin and palmitoylethanolamide as a short-term prophylaxis for menstrual migraine in a real-world clinical setting, a retrospective observational study without a control group was conducted in five Italian centers between May 2023 and June 2025. Methods: Clinical records of 800 women were reviewed, and 220 patients receiving perimenstrual supplementation with phycocyanin and palmitoylethanolamide were screened. Sixty-one women diagnosed with migraine without aura, according to the International Classification of Headache Disorders, met all inclusion criteria and were analyzed. Phycocyanin and palmitoylethanolamide were taken at a dosage of two capsules daily from five days before to five days after the onset of menstruation for three consecutive months. Outcomes during the perimenstrual window were compared with a three-month period without supplementation. Primary outcomes included migraine severity, frequency, and duration of the attacks; secondary outcomes included analgesic consumption and menstrual migraine-associated symptoms. Results: Among the 61 included patients, phycocyanin and palmitoylethanolamide supplementation was associated with a significant reduction in migraine severity across all monitored perimenstrual days (p < 0.0001). While the overall monthly frequency of migraine attacks did not change, the number of migraine days during the perimenstrual window significantly decreased from the first month of supplementation (p < 0.05). Moreover, migraine duration during the perimenstrual window was significantly reduced at one, two, and three months of phycocyanin and palmitoylethanolamide supplementation compared with baseline. Analgesic use and the number of days with migraine-associated symptoms (nausea, vomiting, photophobia/phonophobia) were also significantly reduced. Treatment was well tolerated. Conclusions: In this real-world retrospective study, perimenstrual supplementation with phycocyanin and palmitoylethanolamide was associated with reduced severity, duration, and perimenstrual frequency of menstrual migraine attacks, along with decreased analgesic use, suggesting a safe and potentially beneficial short-term prophylactic strategy for women with menstrual migraine. 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