Search Results (482)

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

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: 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: 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

Vestibular migraine (VM) commonly causes recurrent vertigo, but diagnosing and managing it can be difficult due to symptom overlap with other vestibular and headache disorders. This review provides a comprehensive update on VM, beginning with the diagnostic criteria established by the International Headache Society and the Bárány Society, who have increased awareness of this condition. While the pathophysiology is not yet completely understood, there is evidence of a complex interaction between the nociceptive and vestibular systems. Treatment approaches are primarily empirical and lack robust, high-quality evidence. Often, antihistamines and benzodiazepines are used for quick symptom relief, while the efficacy of triptans is still uncertain. Preventive measures include lifestyle changes, vestibular rehabilitation, oral migraine prophylactics, Botulinum toxin type A, and, more recently, CGRP-targeted therapies. Due to diagnostic uncertainties and the absence of standardised treatment protocols, further research—particularly randomised controlled trials—is crucial for establishing evidence-based guidelines. Full article

The review compares the principles of organization of the brain and immune system, two important organs developed over 500 million years in multicellular organisms, including humans. It summarizes the latest results from research in neurosciences and immunology concerning intercellular communication. While in the brain, intercellular communication is primarily based on exchange of electrical signals, this is not the case in the immune system. The question, therefore, arises as to whether nature developed two entirely different systems of organization. It will be demonstrated that a few basic principles of brain and immune responses are organized in a different way. A majority of intercellular communications, however, such as the formation of synapses, are shown to have many similarities. Both systems are intimately interconnected to protect the body from the1 dangers of the outside and the inside world. During homeostasis, all systems are in regulatory balance. A new hypothesis states that the central systems surrounded by bone, namely the central nervous system (CNS) and the central immune system (CIS), are based on three types of stem cells and function in an open but autonomous way. T cell immune responses to antigens from blood and cerebrospinal fluid protect the system and maintain neuroimmune homeostasis. The newly discovered tunneling nanotubes and extracellular vesicles are postulated to play an important role in crosstalk with already known homeostasis regulators and help in cellular repair and the recycling of biologic material. Three examples are selected to illustrate dysfunctions of homeostasis, namely migraine, multiple sclerosis, and brain cancer. The focus on these different conditions provides deep insights into such neurological and/or immunological malfunctions. Technological advances in neurosciences and immunology can enable neuroimmunomodulation and the development of new treatment possibilities. Full article

Objectives: This study aims to identify the effectiveness of exercise in chronic tension-type headache and chronic migraine. Methods: The PICOS (Population, Intervention, Comparator, Outcomes, Study design) strategy was followed, where P—patients with chronic tension-type headache or chronic migraine; I—exercise; C—conventional treatment; O—pain reduction; and S—RCTs (randomized controlled trials) and quasi-experimental trials. Studies with a high risk of bias according to the RoB 2 (Risk of Bias) scale and with a score < 6 according to the PEDro (Physiotherapy Evidence Database) scale were excluded. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement was followed. The databases Pubmed, Web of Science, and Scopus were searched in November 2024. The PEDro and RoB2 scales were used to assess the risk of bias and internal validity of the studies. The results were synthesized qualitatively. Results: Ten studies with a total sample of 848 subjects were analyzed, comparing therapeutic interventions with an exercise versus conventional treatment. In most of the studies, the exercise group significantly outperformed the control group in pain reduction. Discussion: The findings suggest that exercise improves central pain modulation and reinforces the potential of body strategies such as postural integration. The main limitations found were the limited evidence on exercise’s role in chronic tension-type headache or migraine and the risk of bias due to the difficulty of blinding patients, therapists, and evaluators. Conclusions: The studies analyzed have shown that exercise could be an effective strategy to support the management of chronic tension-type headache and migraine. Full article

Magnesium is an essential mineral involved in hundreds of biochemical reactions, with particular relevance to maintaining neural homeostasis, modulating neurotransmitter systems, and regulating inflammatory and oxidative stress mechanisms. This comprehensive review aims to evaluate the potential role of magnesium in the pathophysiology and treatment of three prevalent neurological and psychiatric disorders—depression, migraine, and Alzheimer’s disease—as well as its broader implications for cognitive health. Current research suggests that magnesium deficiency is associated with the development of depression, as magnesium influences glutamatergic and GABAergic neurotransmission, as well as the activity of the hypothalamic–pituitary–adrenal (HPA) axis, both of which play critical roles in stress responses and mood regulation. Additionally, magnesium’s anti-inflammatory properties may contribute to the alleviation of depressive symptoms. In the context of migraine’s pathophysiology, magnesium plays a role in regulating cerebral vascular tone, modulating the trigeminovascular system, and reducing neuronal hyperexcitability, which may explain the observed correlation between magnesium levels and the incidence of migraines. Regarding Alzheimer’s disease, preclinical and epidemiological studies suggest that magnesium may contribute to modulating neurodegenerative processes and preserving cognitive function; however, due to the heterogeneity of the current findings, further longitudinal and interventional studies are necessary to determine its precise clinical relevance. This review aims to enhance the understanding of the relationship between magnesium and these disorders through a narrative review of relevant clinical studies. The findings may provide insights into the potential therapeutic applications of magnesium and guide the future directions of the research into the prevention and treatment of depression, migraine, and Alzheimer’s disease and overall cognitive health. Full article

Background: Hypothyroidism is defined as a deficiency of thyroid hormones and is further classified into primary, secondary, and tertiary types, based on the root cause of the deficiency. Migraine is a primary headache disorder, characterized by unilateral, pulsating pain, lasting from 4 to 72 h, accompanied by symptoms such as photophobia, phonophobia, nausea, and emesis and sometimes preceded by specific aura phenomena. Both diseases are more prevalent in women than in men. While the primary focus of this systematic review was on the relationship between hypothyroidism and migraine, we also included relevant data on headaches in general when they provided valuable context or mechanistic insight. Methods: This systematic review aimed to summarize the current knowledge about the relationship between migraine and hypothyroidism. The Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines were applied. Screening of two databases led to including 29 relevant studies in the review. Results: Studies demonstrated that migraine and disturbed thyroid function may influence one another. The positive correlation between migraine and hypothyroidism, mainly Hashimoto’s disease, was presented in several studies. Moreover, some research identified this correlation in pediatric populations. Finally, the effects of levothyroxine use, a treatment applied in hypothyroidism, on migraine course were presented. Conclusions: A better understanding of the correlation between migraine and hypothyroidism may lead to an increase in the understanding of the pathogenesis of both disorders and positively impact clinical practice. Full article