Search Results (1,124)

Orofacial pain encompasses a spectrum of disorders ranging from musculoskeletal disorders, such as myofascial pain, and temporomandibular disorders to neuropathic situations, such as trigeminal neuralgia and painful post-traumatic trigeminal neuropathy, and neurovascular pain such as orofacial migraine and cluster orofacial pain. Each require tailored prophylactic pharmacotherapy, such as carbamazepine, gabapentin, pregabalin, amitriptyline, metoprolol, and topiramate. Yet a substantial subset of patients remains refractory. Botulinum toxin type A (BoNT-A) has demonstrated growing efficacy in the treatment of multiple forms of orofacial pain, which covers the whole range of these disorders. We describe the analgesic properties of BoNT-A for each of the three following orofacial pain disorders: neuropathic, myofascial, and neurovascular. Then, we conclude with a section on the neuromodulatory mechanisms of BoNT-A. This lays the basis for the generation of a hypothesis for the segmental therapeutic action of BoNT-A on the whole range of orofacial pain disorders. In addition, the advantage of BoNT-A for providing a safe sustained effect after a single application for chronic pain prophylaxis is discussed, as opposed to the daily use of current conventional prophylactic medications. Finally, we summarize the clinical applications of BoNT-A for chronic orofacial pain therapy. Full article

Background: Few studies have examined exercise-based treatments for migraine and tension-type headache (TTH), and even fewer have focused on strength training and chronic headache, as these present greater challenges. Objectives: This study aimed to evaluate the effectiveness of a group-based neck and shoulder strength training intervention combined with postural correction for patients with chronic headache. Methods: This prospective, single-arm, uncontrolled pilot study with a pre–post design included patients with chronic migraine (n = 10) and TTH (n = 12) who participated in an 8-week group-based program consisting of neck and shoulder strength training three times per week, along with instructions for postural correction. The primary outcome was change in headache frequency. Secondary outcomes included changes in the intensity and duration of headache, number of days of analgesic use, and functionality. Results: In total, 22 patients completed the intervention and were included in the analysis. Headache frequency decreased at follow-up for the overall group (r = 0.531; p = 0.014). In-depth analysis showed that 45% of participants experienced an average reduction of 38% in headache frequency. Additionally, large to moderate effect sizes were observed for the secondary outcomes. Conclusions: This is the first study to introduce a group-based exercise program targeting the neck and shoulder muscles, combined with postural correction and standard pharmacological treatment, for patients with chronic primary headache. It was found to be a safe, well-tolerated, useful, and promising intervention for improving headache frequency, duration, and functionality. Full article

Background: Hemiplegic migraine (HM) is a rare and severe subtype of migraine with a complex genetic basis. Although pathogenic variants in CACNA1A, ATP1A2, and SCN1A explain some familial cases, a significant proportion of patients remain genetically undiagnosed. Increasing evidence points to an overlap between migraine and cerebral small vessel disease (SVD), implicating vascular dysfunction in HM pathophysiology. Objective: This study aimed to identify rare or novel variants in genes associated with SVD in a cohort of patients clinically diagnosed with HM who tested negative for known familial hemiplegic migraine (FHM) pathogenic variants. Methods: We conducted a case-control association analysis of whole exome sequencing (WES) data from 184 unrelated HM patients. A targeted panel of 34 SVD-related genes was assessed. Variants were prioritised based on rarity (MAF ≤ 0.05), location (exonic/splice site), and predicted pathogenicity using in silico tools. Statistical comparisons to gnomAD’s Non-Finnish European population were made using chi-square tests. Results: Significant variants were identified in several SVD-related genes, including LRP1 (p.Thr4077Arg), COL4A1 (p.Pro54Leu), COL4A2 (p.Glu1123Gly), and TGFBR2 (p.Met148Leu and p.Ala51Pro). The LRP1 variant showed the strongest association (p < 0.001). All key variants demonstrated pathogenicity predictions in multiple computational models, implicating them in vascular dysfunction relevant to migraine mechanisms. Conclusions: This study provides new insights into the genetic architecture of hemiplegic migraine, identifying rare and potentially deleterious variants in SVD-related genes. These findings support the hypothesis that vascular and cellular maintenance pathways contribute to migraine susceptibility and may offer new targets for diagnosis and therapy. Full article

Many headaches at night arise due to primary headache disorders, which occur independently of other symptoms and are not caused by another medical condition. Primary headache disorders with nighttime attacks can include tension-type headaches, migraines, hypnic headaches, and cluster headaches. A hypnic headache is sometimes called an “alarm clock headache” because symptoms tend to arise at the same time of night. Apart from considering primary headaches, secondary causes of nighttime headaches should be considered and ruled out, in particular headaches secondary to intracranial hypertension, temporomandibular joint issues (like bruxism) and sleep apnea. Treatments vary based on headache type but often include a combination of medications and prevention strategies. This review article covers the basics of nighttime primary headaches in children, including pathophysiology, etiology, clinical features of the different forms and their treatment. It will also discuss the differences in headache features between children and adults. Full article

Background/Objectives: Migraine is a debilitating neurologic disorder with diet-related triggers. No studies exist on education on migraine in conjunction with an elimination diet as a non-pharmacologic management approach. Methods: Higher education students who self-reported migraine were enrolled in this observational, pilot feasibility study. At baseline, participants completed questionnaires on demographics, migraine disability, and their understanding of migraine and an elimination diet. After one month of self-paced, asynchronous, online modules, participants were reassessed on their understanding of migraine and an elimination diet. Two months later, participants completed follow-up questionnaires on migraine disability, whether they implemented components of the diet, and any barriers they encountered. Results: Of 66 students who completed baseline measures, 33 completed the modules and all questionnaires. Of participants who completed the study, 100% found the modules helpful in learning about migraine and an elimination diet; 57.6% incorporated aspects of the elimination diet into their lives. Participants had significant (p < 0.001) increases in knowledge both about migraine and an elimination diet. Participants had a potentially clinically significant decrease (14-point MIDAS drop, p = 0.10) in migraine symptoms after completing the educational intervention, with a greater decrease among participants who implemented the elimination diet. Conclusions: It is feasible to design and implement an education intervention on diet for higher education students, though loss to follow-up was high in this population. The majority of participants who completed the modules adopted aspects of an elimination diet, indicating its feasibility. Further studies with a larger sample size powered to assess the efficacy of this approach are needed. Full article

Background/Objectives: Migraine affects approximately 3–10% of school-aged children and up to 28% of adolescents, with prevalence increasing during adolescence. For pediatric specialty providers, increased awareness of this condition may influence patient care. This study examined pediatric dentists’ education, clinical exposure, and perceived knowledge gaps related to pediatric migraine, with the goal of identifying barriers to recognition and referral, as well as informing future training to support accurate diagnosis and interdisciplinary care. Methods: A 28-item electronic questionnaire was distributed to all members of the American Academy of Pediatric Dentistry, including pediatric dentists and postgraduate pediatric dental residents, assessing knowledge, beliefs, clinical experience, and interest in further training regarding pediatric headache/migraine management. Respondents with and without previous training were compared in terms of general understanding using t-tests; a linear regression model analyzed predictors of provider awareness regarding links between oral conditions and headache/migraine. Results: Among 315 respondents, the mean self-perceived awareness score was 2.7 ± 1.3 (on a 0–5 scale). The most frequently identified contributing factors were clenching (73.7%), bruxism (72.4%), and temporomandibular disorders (65.7%). Nearly all respondents (95.2%) reported no formal education on headache/migraine prevention, yet 78.1% agreed on the importance of understanding the relationship between oral health and headache/migraine. Respondents with prior training were significantly more aware (p < 0.001) than those without prior training. Educating families (p < 0.001), frequency of patient encounters with headache (p = 0.032), coordination with healthcare providers (p = 0.002), and access to appropriate management resources (p < 0.001) were significant predictors of providers’ awareness. Conclusions: Pediatric dental providers expressed strong interest in enhancing their knowledge of headache/migraine management, highlighting the value of integrating headache/migraine-related education into training programs and promoting greater interdisciplinary collaboration. Full article

Background: Pediatric-onset multiple sclerosis (POMS) is a rare but often more aggressive form of multiple sclerosis, associated with early cognitive impairment and significant impact on quality of life. Multiple sclerosis and primary headaches, particularly migraine, are well established in adults, but data on pediatric populations remain limited. Methods: The purpose of this retrospective study was to examine 64 POMS patients, divided into groups with and without headaches, to determine potential correlations between headache presence, age at POMS onset, and MRI lesion burden. Results: Headaches were reported by 78% of patients, predominantly migraines (68%), with a significantly higher prevalence in females (74%). No significant differences were found in age at MS onset or lesion load on brain MRI between patients with and without headaches. Among those with headaches, migraines represented a higher frequency of attacks and a greater need for prophylactic treatment compared to other headache types. Headache characteristics, including pain location and associated symptoms, showed no correlation with age at MS onset or lesion burden. Conclusions: These findings indicate that while headaches are common in POMS and more frequent in females, their presence and features do not appear to directly influence the clinical or neuroradiological course of the disease. Further research with larger cohorts and longitudinal follow-up is warranted to better understand the underlying mechanisms and long-term impact of headaches in pediatric MS. Full article

Background/Objectives: Cognitive dysfunction is frequently observed in chronic migraine (CM) patients, but the contributing medical and psychological factors remain unclear. This study investigated associations between the cognitive reserve and medical, psychological, and lifestyle factors in individuals with CM. Methods: A retrospective review was conducted at a tertiary referral center in Taiwan. Cognitive function was evaluated via the mini-mental state examination (MMSE), while anxiety and depression were evaluated via the Beck Anxiety and Depression Inventories. Clinical variables included monthly headache days, headache intensity (numerical rating scale), migraine-related disability, and use of preventive medications. Multivariable linear regression analyses were performed to identify independent predictors of the cognitive reserve after adjusting for relevant covariates. Results: Among 50 participants (86.0% women; mean age 42.48 ± 13.47 years), six (12.0%) exhibited objective cognitive impairment (MMSE < cutoff). After a covariate adjustment, higher headache intensity was significantly associated with a lower cognitive reserve in anxiety and depression models. Patients with objective cognitive impairment reported significantly higher levels of pain, anxiety, and depression. Conclusions: The headache intensity, anxiety, and depression were significantly linked to a lower cognitive reserve in CM patients. These findings highlight the importance of incorporating routine psychological and cognitive assessments in CM care and suggest potential targets for integrative treatment strategies. Full article

Background: Cannabidiol (CBD) has demonstrated potential as a therapeutic agent for muscle tension, pain, and sleep bruxism, yet its broader impact on comorbid conditions such as sleep disturbance and migraine disability remains underexplored. This study aimed to assess the effects of topical CBD on sleep quality and migraine-related disability in patients with bruxism-associated muscular pain. Methods: In a randomized, double-blind clinical trial, 60 participants with bruxism were allocated equally into three groups: control (placebo gel), 5% CBD gel, and 10% CBD gel. Participants applied the gel intraorally to the masseter muscles nightly for 30 days. Sleep quality and migraine-related disability were assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Migraine Disability Assessment Scale (MIDAS), respectively. Surface electromyography (sEMG) and the Bruxoff^® device were used for objective evaluation of muscle tension and bruxism intensity. Results: Both CBD treatment groups demonstrated statistically significant improvements in PSQI and MIDAS scores compared to the control group (p < 0.001). No significant differences were observed between the 5% and 10% CBD groups, suggesting comparable efficacy. The sEMG findings corroborated a reduction in muscle tension. Improvements in sleep and migraine outcomes were positively correlated with reductions in muscle activity and pain. Conclusions: Topical CBD gel significantly improved sleep quality and reduced migraine-related disability in patients with bruxism-associated muscular pain, supporting its role as a multifaceted therapeutic option in the management of TMD and related comorbidities. Further research is needed to confirm long-term benefits and determine optimal dosing strategies. Full article

Background: Migraine is a highly prevalent and disabling neurological disorder among university students that has significant impacts on personal and socioeconomic levels. Despite its impact, migraine remains underdiagnosed and undertreated. Objective: This study aimed to estimate the prevalence of probable migraine among university students in Greece and explore its association with sociodemographic data. Methods: A cross-sectional, questionnaire-based study was conducted between September 2023 and January 2024 among university students in Greece using a convenience sampling method. The Headache Screening Questionnaire—English Version (HSQ-EV) was used to screen for probable migraine, along with additional questions assessing demographic characteristics. Descriptive statistics and bivariate analyses were performed. Results: The prevalence of probable migraine was 20%. Female students were more likely to experience migraine compared to males. Migraine was also statistically significantly associated with marital status and employment status. In a multivariate logistic regression model including sex assigned at birth, age, educational level, marital status, and employment status, older age was independently associated with higher odds of migraine. Conclusions: Migraine is a prevalent health issue among university students in Greece, with clear gender and sociodemographic associations. Future studies with larger, more representative sample sizes and the use of validated diagnostic tools are needed to understand its determinants and inform targeted interventions. Full article

Background: Valproic acid (VPA) is a medication used to treat epilepsy, bipolar disorder, and migraine. If taken during pregnancy, it can cause neural tube defects (NTDs) and leads to offspring ASD behavioral phenotype. It has recently been found that early postnatal VPA exposure can also induce the ASD phenotype, but the details of model production and intervention still need further investigation. Dimethylmalonic acid (DMM), a competitive inhibitor of succinate dehydrogenase, blocks the key element succinate of OXPHOS, decreasing the secretion of anti-inflammatory cytokines and ROS production. However, it is still unclear whether DMM is involved in the repair of developmental brain injuries. Objectives: The aim of this study was to evaluate the intervention effect and optimal dosage of DMM on behavioral phenotypes using a neonatal mouse VPA autism model. Methods: This experiment consists of two parts. The first part observed the effects of different concentrations of VPA on the development and neurobehavioral phenotype of mice. The second part determined the intervention effect of DMM on a developmental VPA autism model and determined the optimal therapeutic dose. Results: We found that the 40 mg/mL concentration had a greater impact on the neural reflex damage in mice. Moreover, DMM treatment can partially improve the neurobehavioral damage in the VPA model, and 20 mg/kg has the best intervention effect. Conclusions: This study provides valuable model construction data for further exploring the mechanism of DMM treatment for an ASD phenotype induced by VPA exposure in neonates. Full article

Migraine is a neurovascular paroxysmal disorder characterized by neurogenic inflammation and has a remarkable impact on the quality of life. The Food and Drug Administration (FDA) approved onabotulinumtoxin A in 2010 for the prophylactic treatment of chronic migraine. Today, in its 4th decade, it is approved in 100 countries for 15 main indications. Its mechanism of action, based on the inhibition of neurotransmitter release from primary sensory neurons, is very complex: it affords antinociception, but it also has an analgesic effect on neuropathic pain conditions and reduces the need for rescue medications. Genetic variants have been investigated for their potential role in the pathogenesis and clinical expression of migraine and of the response to treatments. These studies primarily involved genes associated with vascular regulation and cardiovascular pathology, including those encoding angiotensin-converting enzyme (ACE) and methylenetetrahydrofolate reductase (MTHFR). However, epigenetics and, particularly, genetic and epigenetic modifications are still poorly studied in terms of understanding the mechanisms implicated in susceptibility to migraine, aura, chronification and response to symptomatic and preventive treatments. In particular, the aim of the present study is to gather evidence on the genetic variants and epigenetic modifications affecting the pathway of the calcitonin gene-related peptide (CGRP), the target of onabotulinumtoxin A and of all the novel monoclonal antibodies. Full article

Background and Objectives: Medication overuse headache (MOH) presents unique clinical challenges in older adults due to age-related changes and comorbidities. However, data on MOH characteristics and treatment responses in this population remain limited. This study investigated the clinical features, treatment patterns, and short-term outcomes of MOH in older patients. Methods: We analyzed data from the RELEASE registry, a nationwide, multicenter prospective cohort of MOH patients in South Korea. Participants were stratified into older (≥65 years) and younger (<65 years) groups. We compared clinical features, treatment patterns, and 3-month outcomes, and identified factors associated with treatment response in the older group. Results: Among 791 patients, 72 (9.1%) were older. Compared to younger patients, older patients reported more monthly headache days (30.0 vs. 27.0, p = 0.012), more days using acute medication (30.0 vs. 20.0, p < 0.001), and fewer headache-free days (0.0 vs. 3.0, p = 0.012). They also experienced more severe headache days (12.5 vs. 10.0, p = 0.056). Despite this, older patients showed lower disability, with significantly lower Migraine Disability Assessment scores (30.0 vs. 46.0, p < 0.001) and a trend toward lower Headache Impact Test-6 scores (64.5 vs. 66.0, p = 0.065). In multivariable analysis, poor adherence to preventive treatment (≤24%) was significantly associated with non-response (OR 0.13, 95% CI: 0.02–0.96, p = 0.045) at 3 months. Conclusions: Older patients with MOH showed distinct clinical features, including higher headache frequency and severity but relatively lower disability. Improving adherence to preventive treatment may enhance treatment response. Age-specific management strategies are needed. Full article

The prevalence of stroke in patients with migraine is higher than in the general population, suggesting certain shared mechanisms of pathogenesis. Migrainous infarction is a pronounced example of the migraine–stroke connection. Some cases of migraine with aura may be misdiagnosed as stroke, with subsequent mistreatment. Therefore, it is important to identify these shared mechanisms of pathogenesis contributing to the migraine–stroke connection to improve diagnosis and treatment. Sirtuins (SIRTs) are a seven-member family of NAD⁺-dependent histone deacetylases that can epigenetically regulate gene expression. Sirtuins possess antioxidant properties, making them a first-line defense against oxidative stress, which is important in the pathogenesis of migraine and stroke. Mitochondrial localization of SIRT2, SIRT3, and SIRT4 supports this function, as most reactive oxygen and nitrogen species are produced in mitochondria. In this narrative review, we present arguments that sirtuins may link migraine with stroke through their involvement in antioxidant defense, mitochondrial quality control, neuroinflammation, and autophagy. We also indicate mediators of this involvement that can be, along with sirtuins, therapeutic targets to ameliorate migraine and prevent stroke. Full article

Background: HM is a rare, severe form of migraine with aura, characterised by motor weakness and strongly influenced by genetic factors affecting the brain. While pathogenic variants in CACNA1A, ATP1A2, and SCN1A genes have been implicated in familial HM, approximately 75% of cases lack known pathogenic variants in these genes, suggesting a more complex genetic basis. Methods: To advance our understanding of HM, we applied a variant prioritisation approach using whole-exome sequencing (WES) data from patients referred for HM diagnosis (n = 184) and utilised PathVar, a bioinformatics pipeline designed to identify pathogenic variants. Our analysis incorporated two strategies for association testing: (1) PathVar-identified single nucleotide variants (SNVs) and (2) PathVar SNVs combined with missense and rare variants. Principal component analysis (PCA) was performed to adjust for ancestral and other unknown differences between cases and controls. Results: Our results reveal a sequential reduction in the number of genes significantly associated with HM, from 20 in the first strategy to 11 in the second, which highlights the unique contribution of PathVar SNVs to the genetic architecture of HM. PathVar SNVs were more distinctive in the case cohort, suggesting a closer link to the functional changes underlying HM compared to controls. Notably, novel genes, such as SLC38A10, GCOM1, and NXPH2, which were previously not implicated in HM, are now associated with the disorder, advancing our understanding of its genetic basis. Conclusions: By prioritising PathVar SNVs, we identified a broader set of genes potentially contributing to HM. Given that HM is a rare condition, our findings, utilising a sample size of 184, represent a unique contribution to the field. This iterative analysis demonstrates that integrating diverse variant schemes provides a more comprehensive view of the genetic factors driving HM. Full article