Cephalalgia最新文献

BackgroundChronic migraine (CM) is highly disabling, and many patients fail to respond to monotherapy with approved preventive treatments. OnabotulinumtoxinA (BoNTA) and atogepant act on distinct but complementary targets within the trigeminovascular system and may exert additive or synergistic effects when used together. Real-world data on their combination remain scarce.MethodsWe prospectively analyzed adult patients with CM who had received at least three prior BoNTA cycles and initiated atogepant 60 mg/day for a minimum of 24 weeks as add on to BoNTA. Co-primary outcomes were changes in monthly migraine days (MMDs) and ≥50% response rate at 24 weeks. Secondary outcomes included disability, medication use, tolerability and subgroup comparisons by prior monoclonal antibodies exposure.ResultsAmong 101 patients, 82 completed 24 weeks of co-treatment. Mean MMDs decreased by 6.5 days (p < 0.001) and 45.1% of patients achieved a ≥50% reduction. Acute medication days decreased by 6.0 (p < 0.001) and Headache Impact Test-6 scores improved significantly (mean change: -4.0; p < 0.001). Patient's Global Impression of Change scores indicated moderate-to-great improvement. Anti-calcitonin gene-related peptide naïve patients experienced larger reductions in MMDs (-7.75 vs. -5.87) and disability scores compared to non-naïve patients. Multivariable analysis identified only baseline acute medication use as predictor of response. Adverse events were mild and consistent with known safety profiles for both drugs separately; no novel safety concerns emerged.ConclusionsThe addition of atogepant to BoNTA might be effective and well tolerated in real-world setting, including CM patients previously exposed to multiple preventives. Prospective controlled trials and health-economic evaluations are warranted to validate these observations and inform future clinical guidelines.

BackgroundIt is becoming increasingly evident that the vasculature is implicated in migraine pathophysiology. Calcitonin gene-related peptide (CGRP) acts as one of the key migraine mediators through various mechanisms that includes endothelium-mediated cerebral vessel vasodilation. Endothelial cells express mechanosensitive Piezo1 channels and have been suggested to play a role in migraine pathophysiology. However, the crosstalk between these two migraine-related signalling pathways remains unclear.MethodsWe measured intracellular calcium (Ca²⁺) in human induced pluripotent stem cell-derived endothelial cells (hiPSC-ECs), after exposure to Yoda1, a specific Piezo1 channel agonist, with and without CGRP. In addition, we investigated the effects of CGRP and Yoda1 on cellular remodelling by staining for focal adhesion (FA) protein paxillin using immunocytochemistry.ResultsOur data suggest that a one-hour sensitization of hiPSC-ECs with CGRP followed by application of Yoda1 leads to a higher intracellular Ca²⁺ level compared to when Yoda1 and CGRP are acutely applied separately or combined, suggesting at least indirect crosstalk between the two signalling pathways in the vascular system. CGRP receptor antagonist BIBN4096 significantly reduced the intracellular Ca²⁺ level under this sensitization protocol, confirming effective CGRP pathway blockade. The results also show that a one-hour sensitization of CGRP and Piezo1 activation affects cellular remodelling as evidenced by an increased number and area size of paxillin FA points per cell in hiPSC-ECs.ConclusionsWe have generated a human cell assay based on iPSC-derived endothelial cells and provided some evidence for crosstalk between mechanosensitive Piezo1 channels and CGRP in our hiPSC-EC system, which shows the potential for in vitro modelling of vascular implications relevant to migraine.

BackgroundGreater occipital nerve block (GONB) has become an established treatment for migraine. Though numerous systematic reviews and randomised control trials (RCTs) are cited as supporting evidence, the quality and consistency of this data remains unclear.MethodsAn umbrella review of systematic reviews investigating GONB for migraine was conducted. Additionally, an independent systematic review and meta-analysis of relevant RCTs was performed in accordance with PRISMA guidelines. Both evaluated MEDLINE ('PubMed'), Embase, and CENTRAL databases.ResultsNine relevant systematic reviews were identified; all had significant limitations and/or contained methodological errors. The reviews had been cited 256 times. None were eligible for statistical analysis.Sixteen RCTs (930 patients) and seven RCTs (401 patients) were included for qualitative and quantitative analyses respectively. Studies were heterogeneous in their methodologies. No serious adverse effects were identified. With moderate certainty, local anaesthetic (LA) GONB reduces headache severity in acute migraine attacks at 30 min (-2.08; p < 0.001). With low certainty, weekly bilateral LA GONB injections reduce headache severity (-1.33; p < 0.001) and monthly headache days (-4.46; p < 0.001) at one month for chronic migraine. Sustained benefits of GONB remain unclear. Data was insufficient to analyse the efficacy of steroid GONB, LA-steroid GONB, nor unilateral GONB for chronic migraine, and GONB - of any type - for episodic migraine.ConclusionsThere is limited RCT evidence supporting GONB for the treatment of migraine. Existing systematic reviews should be interpreted with caution. RCTs with homogeneous methodologies are required to evaluate GONB in the management of disability in migraine.Trial RegistrationPROSPERO registration ID: CRD42024595492.

BackgroundEvoked potentials are widely used to investigate sensory and nociceptive processing abnormalities in migraine. However, electrophysiological distinctions between migraine subtypes remain insufficiently characterized in the literature. The aim was to systematically review and summarize neurophysiological abnormalities in evoked potential studies (visual, auditory, brainstem, somatosensory and laser) in migraine patients, with a particular focus on latency, amplitude, habituation and clinical correlations across subtypes and healthy controls.MethodsFollowing PRISMA guidelines, we searched PubMed, EMBASE and Web of Science for studies, terms included "Migraine Disorders," "Migraine," "Vestibular Diseases" and "Evoked Potentials", which were published from 2000 to 2024 were included. Risk of bias was assessed using a modified Newcastle-Ottawa Scale.ResultsIn total, 813 studies were screened, resulting in 55 studies meeting the inclusion criteria. Patients with migraine with aura demonstrated higher amplitudes and asymmetry of visual evoked potentials compared to those with migraine without aura. Habituation deficits were particularly evident across all types of evoked potentials. A few studies compared chronic and episodic migraine, reporting higher brainstem and somatosensory evoked potential amplitudes in chronic migraine.ConclusionsMigraine patients have a consistent habituation deficit on all evoked potential parameters. Migraine with aura and chronic migraine may have higher cortical excitability. Further research with larger sample sizes, standardized methodologies and an accurate comparison of migraine phases will enlighten our understanding of the migraine subtypes.Trial RegistrationPROSPERO ID: CRD42024502803.

BackgroundMany guidelines list migraine with aura (MwA) as a contraindication to estrogen-containing combined hormonal contraceptives (CHCs) due to vascular risks. However, current evidence is based on small sample studies with potential influence by confounding factors. Additionally, few studies have examined the vascular risk associated with modern CHCs with lower dose estrogen, particularly in relation to aura status. The present study aims to investigate the vascular risk of modern CHCs in women with migraine with and without aura.MethodsWe used a de-identified electronic medical record database with 120 million patients across multiple health systems in the United States of America. We included female patients aged 18-45 years who received a migraine diagnosis code, had at least three office visits within three years, and were prescribed at least one migraine-specific medication within 6 months following the first outpatient visit. All data after 2010 were included. Patients with prior cardiovascular events were excluded. Our composite endpoint consisted of acute ischemic stroke, acute myocardial infarction, deep vein thrombosis/pulmonary embolism and intravenous thrombolytic administration. We stratified our analysis according to CHC exposure and aura status and compared the incidence of the endpoint with high-dimensional propensity score-matching between CHC users and non-users in (i) the overall cohort, (ii) MwA and (iii) migraine without aura (MwoA); between MwA and MwoA in (iv) patients prescribed CHCs; and in (v) those without CHC prescriptions.ResultsWe included 5535 patients who received CHC prescriptions and 21,520 who did not. 114 (2.06%) of CHC users and 547 (2.54%) of CHC non-users had at least one vascular event. With propensity score-matched comparison, the composite endpoint did not significantly differ between CHC and non-CHC in the overall migraine group, those with MwA and the MwoA group. In those prescribed CHC, MwA and MwoA did not differ in all the outcomes. For CHC non-users, MwA was associated with a higher incidence of acute ischemic stroke (hazard ratio = 2.45; 95% confidence interval = 1.58-3.78; p < 0.001; n = 6201 in each group) and the composite endpoint (hazard ratio = 1.34; 95% confidence interval = 1.08-1.67; p = 0.008).ConclusionsOur real-world study showed that exposure to modern CHC was not associated with a significant increase in vascular risk in women aged 18-45 years with migraine, MwA or MwoA who have no prior cardiovascular events. However, in those who never received CHC, MwA was associated with higher vascular risks compared to MwoA. While limitations exist using large scale electronic medical record databases for analysis, our results suggest that carefully designed prospective studies should be conducted to reassess the vascular risk associated with CHC use in women with migraine, especially MwA.

AimThe diagnostic criteria for chronic migraine, which are based on the total number of monthly headache days, are the subject of ongoing debate. The present study aimed to investigate and compare the burden of disease and quality of life between high-frequency episodic migraine and chronic migraine, using data from the large population-based PopHEAD study.MethodsPopHEAD is a population-based cross-sectional study in the Norwegian county of Vestfold and Telemark performed in 2023. Among 28,753 randomly selected adults (aged 18-70 years) invited to complete an electronic questionnaire, 8265 (28.7%) participants responded. The questionnaire was a modified version of the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation questionnaire, and migraine was classified using a diagnostic algorithm that has been validated by telephone interview in this population. High-frequency episodic migraine was classified according to newly proposed criteria, and chronic migraine according to International Classification of Headache Disorders, 3rd edition (ICHD-3) criteria. Using linear regression for continuous variables and logistic regression for binary outcomes, we compared the disease burden and quality of life between participants classified with high-frequency episodic migraine and those with chronic migraine. The analysis was conducted in two steps: a primary analysis adjusted for age and sex, as well as a second analysis with an additional adjustment for monthly migraine days.ResultsOf the 8265 responders, 225 had high-frequency episodic migraine and 349 had chronic migraine. Compared to the high-frequency episodic migraine group, the chronic migraine group had more monthly migraine days (17.9 vs. 9.7, p < 0.001) and headache days (20.8 vs. 9.9, p < 0.001). The chronic migraine group also used more acute medication (p < 0.001). In analyses adjusted for age and sex, participants with chronic migraine reported greater disease burden across almost all measures, including work and social impairment, and had a lower quality of life (p < 0.01). With additional adjustment for monthly migraine days, no significant differences in disease burden were found between the two groups, except from days missed from household work (p = 0.03).ConclusionsThe higher disease burden observed in chronic migraine compared to high-frequency episodic migraine was fully explained by the higher number of monthly migraine days in the chronic migraine group. Our findings support previous suggestions to simplify the ICHD-3 criteria for chronic migraine by basing it solely on the number of monthly migraine days.

BackgroundEmerging evidence highlights the role of microRNAs (miRNAs) in epigenetic mechanisms related to migraine pain. The expression of miR-382-5p and miR-34a is higher in serum and peripheral blood mononuclear cells of people with migraine, but limited data is available regarding their possible alteration in other cell subtypes. Several lines of evidence support a monocyte dysfunction in migraine pathophysiology. To gain deeper insights into cell-specific miRNAs expression in migraine individuals with different disease severity, this study aims to determine the expression levels of miR-34a and miR-382-5p in monocytes.MethodsThis cross-sectional, controlled study included 47 participants with episodic migraine (EM, 72.3% females, 41.4 ± 10.7 years), 32 with chronic migraine with medication overuse (CM-MO, 81.3% females, 46.1 ± 10.9 years) and 30 healthy controls (HCs, 66.7% females, 42.9 ± 14.8 years). We assessed interictal monocyte-specific miR-382-5p and miR-34a expression by qRT-PCR, normalizing the expression with U6 RNA (relative quantification - RQ).ResultsmiR-382-5p monocytic expression was higher in EM (4.21 ± 1.41 RQ) and CM-MO (6.80 ± 4.37 RQ) when compared to HCs (2.02 ± 0.64 RQ) (p = 0.005 for all comparisons). miR-34a monocytic expression was higher in EM (4.50 ± 1.62 RQ) and CM-MO (6.47 ± 1.87 RQ) when compared to HCs (1.94 ± 0.81 RQ, p = 0.005 for all comparisons). Expression of miR-382-5p and miR-34a were higher in CM-MO when compared to EM (p = 0.005 for both comparisons). After adjusting for age, sex, ongoing preventive medications, presence of anxiety or depressive symptoms, and smoking habit, a logistic regression model confirmed the differences in the monocytic expression of miR-34a and miR-382-5p between EM and CM-MO participants.ConclusionsOur findings underscore the relevance of miR-34a and miR-382-5p in migraine pathophysiology, as evidenced by their altered expression in monocytes from migraine participants compared to HCs. These miRNAs were also associated with disease severity, being higher in CM-MO when compared to EM individuals.Trial RegistrationThe study protocol was registered at ClinicalTrials.gov (NCT05891808).

Background/AimPost-traumatic headache often resembles migraine or tension-type headache, but distinct phenotype and clinical characteristics necessitate further delineation. We aimed to characterize the clinical phenotype, headache patterns, associated features and comorbidities, medication patterns and functional impact of post-traumatic headache in an adult population following mild traumatic brain injury.MethodsThis is a cross-sectional analysis of a cohort of adults with post-traumatic headache after mild traumatic brain injury, by any mechanism, evaluated by a neurologist at an outpatient specialized concussion and headache center in Ontario, Canada between February 2021 and October 2023. Data were collected through standardized pre- and during-visit questionnaires. Descriptive statistics are presented.ResultsAmong 405 patients assessed by a neurologist for post-traumatic headache, median time since injury was 37 days (IQR: 13-126). Most patients reported headache 26 + days per month (292, 72.1%). Headache was continuous in 114 (28.1%), whereas in 215 (53.1%) it lasted hours to days. Headache location was unilateral in 174 (43.0%) and bilateral in 159 (39.3%). Headache quality was described as pulsating/throbbing in 260 (64.2%). The median severity was 7/10 (IQR 5-8). Aggravation by routine physical activity was reported in 287 (70.9%), nausea/vomiting in 279 (69.0%), photophobia in 358 (88.4%) and phonophobia in 337 (83.2%). There was no positional preference for 147 patients (36.3%), while 216 (53.3%) preferred lying down/reclined. Acute medication use frequency was reported as 3 + days per week in 218 (53.8%) and daily in 143 (35.3%). Within this cohort, 201 (49.6%) endorsed one or more psychiatric comorbidities. Only 66 (16.3%) had returned to full work/school attendance, while 169 (41.7%) were completely off usual occupational activities post-injury. One hundred seventy-eight (44.0%) reported pending litigation or insurance claims related to their injury, and/or having a work-related injury. Among the 183 (45.2%) who had undergone neuroimaging, 160 (87.9%) studies were reportedly normal, while there were 13 (7.1%) incidental findings and eight (4.3%) injury-related.DiscussionWhile select migraine features such as photophobia, phonophobia and worsening with routine physical activity are common in post-traumatic headache, there are also distinct features, including daily or near daily headache of long duration. The latter may suggest early sensitization in post-traumatic headache. There is an associated high risk of medication overuse headache, given frequent administration of acute medications, as well as high rates of psychiatric comorbidities and functional impairment. Future studies should aim to further delineate the longitudinal clinical, pathophysiological, and treatment response differences between post-traumatic headache and primary migraine.

BackgroundMigraine headache and complex regional pain syndrome share mechanisms, such as neuroinflammation, central sensitization and loss of inhibitory pain controls, that could provoke or exacerbate symptoms in both disorders. In the present study, it was hypothesized that headaches would worsen after the onset of complex regional pain syndrome and that limb pain would be more severe in patients with co-morbid headaches than in patients who remained headache-free. Notably, complex regional pain syndrome is associated with ipsilateral cranial symptoms such as photophobia and forehead hyperalgesia. Whether shared mechanisms might drive these symptoms was also explored.MethodsEighty-eight patients with complex regional pain syndrome were asked about their previous and current headache experience. The spatial distribution of pain was quantified from pain drawings, and hyperalgesia to mechanical and thermal stimulation was assessed in the limbs and forehead. In addition, the visual discomfort threshold was measured separately for each eye.ResultsSixty-six percent of patients reported that headaches (primarily migraine) had developed or worsened after the onset of complex regional pain syndrome and 22 percent now had daily or near-daily headaches. Limb pain and hyperalgesia were greater in such cases than in those with stable headaches or who remained headache-free. Photophobia and forehead hyperalgesia were greater ipsilateral than contralateral to symptoms of complex regional pain syndrome in patients with stable or worsening headaches but were symmetrical in headache-free patients. In addition, photophobia was symmetrical in patients with recurrent tension-type headaches. Patients with worsening headaches were younger at the onset of complex regional pain syndrome than patients with stable headaches or who were headache-free, in line with greater vulnerability to migraine in younger than older adults. In a subgroup of patients, the pain of complex regional pain syndrome extended from the upper limb to the ipsilateral dorsal cervical region, a documented source of pain in migraine. However, headaches ipsilateral to complex regional pain syndrome also recurred in patients with lower limb pain, indicating involvement of other pain mechanisms.ConclusionsTogether, the findings indicate that headaches with features of migraine develop after the onset of complex regional pain syndrome. In turn, this is associated with ipsilateral cranial symptoms and heightened limb pain. We suggest that shared pathophysiology increases susceptibility to ipsilateral cranial symptoms and exacerbates pain in both disorders, potentially in a positive loop. Breaking this cycle might permit otherwise intractable symptoms and pain to subside.

BackgroundMigraine and gynecological conditions, such as endometriosis (EDM) and polycystic ovarian syndrome (PCOS), are highly prevalent among females and appear to influence each other, with a potential shared pathophysiological mechanism. Therefore, this study aims to provide a comprehensive summary of the current evidence regarding the relationship between migraine and EDM/PCOS from a clinical perspective.MethodsA systematic review was conducted using four databases (MEDLINE(Pubmed), EMBASE (Elsevier), Web of Science and Cochrane Library) along with searches in the grey literature. The protocol was registered prospectively on the PROSPERO platform (CRD42024628010). The primary search was performed on 4 December 2024. Eligible studies included observational studies that compared two or more groups of females with migraine, EDM and/or PCOS diagnosis. The modified Newcastle-Ottawa Scale was used to assess the quality of the included studies. Data extraction was performed and results systematically analyzed.ResultsFrom an initial 408 identified studies, a final selection of 15 was analyzed (14 focused on EDM and 1 on PCOS) with a total of 289,519 individuals included. All selected studies achieved a score of 6 or higher on the mNOS. When comparing females with and without EDM, the prevalence of migraine reached up to 44.7%, with females affected with EDM having up to a five-fold increased risk of developing migraine (adjusted odds ratio = 5.35, 95% confidence interval = 2.11-16.4). When comparing females with and without migraine, a higher prevalence and risk of EDM was observed, with rates reaching 53.4% and an adjusted odds ratio up to 10.5 (95% confidence interval = 2.2-51.4). Mixed findings were found regarding the influence of EDM on migraine characteristics, as well as the impact of migraine in EDM-related symptoms and disease severity. Females with migraine and EDM exhibited higher scores in disability assessment tools (Headache Impact Test-6, 30-item Endometriosis Health Profile), suggesting a greater disease burden. Due to the limited data, no conclusions could be drawn regarding a link between PCOS and migraine.ConclusionsAlthough further high-quality research is required to better understand the underlying mechanisms linking migraine, EDM and PCOS, the current evidence supports a significant association between migraine and endometriosis.Trial Registration: PROSPERO Registration ID: CRD42024628010.