Redefining migraine prevention: early treatment with anti-CGRP monoclonal antibodies enhances response in the real world.

BACKGROUND: Anti-CGRP monoclonal antibodies (anti-CGRP MAbs) are approved and available treatments for migraine prevention. Patients do not respond alike and many countries have reimbursement policies, which hinder treatments to those who might respond. This study aimed to investigate clinical factors associated with good and excellent response to anti-CGRP MAbs at 6 months. METHODS: European multicentre, prospective, real-world study, including high-frequency episodic or chronic migraine (CM) patients treated since March 2018 with anti-CGRP MAbs. We defined good and excellent responses as ≥50% and ≥75% reduction in monthly headache days (MHD) at 6 months, respectively. Generalised mixed-effect regression models (GLMMs) were used to identify variables independently associated with treatment response. RESULTS: Of the 5818 included patients, 82.3% were females and the median age was 48.0 (40.0-55.0) years. At baseline, the median of MHD was 20.0 (14.0-28.0) days/months and 72.2% had a diagnosis of CM. At 6 months (n=4963), 56.5% (2804/4963) were good responders and 26.7% (1324/4963) were excellent responders. In the GLMM model, older age (1.08 (95% CI 1.02 to 1.15), p=0.016), the presence of unilateral pain (1.39 (95% CI 1.21 to 1.60), p<0.001), the absence of depression (0.840 (95% CI 0.731 to 0.966), p=0.014), less monthly migraine days (0.923 (95% CI 0.862 to 0.989), p=0.023) and lower Migraine Disability Assessment at baseline (0.874 (95% CI 0.819 to 0.932), p<0.001) were predictors of good response (AUC of 0.648 (95% CI 0.616 to 0.680)). These variables were also significant predictors of excellent response (AUC of 0.691 (95% CI 0.651 to 0.731)). Sex was not significant in the GLMM models. CONCLUSIONS: This is the largest real-world study of migraine patients treated with anti-CGRP MAbs. It provides evidence that higher migraine frequency and greater disability at baseline reduce the likelihood of responding to anti-CGRP MAbs, informing physicians and policy-makers on the need for an earlier treatment in order to offer the best chance of treatment success.

Prevalence of cranial autonomic symptoms in frequent episodic tension-type headache: A post hoc analysis of the cross-sectional Migraine in Poland study.

BACKGROUND: Cranial autonomic symptoms (CASs) include lacrimation, conjunctival injection, rhinorrhea, nasal congestion, facial flushing or sweating, ptosis, and myosis. These symptoms may be associated with trigeminal autonomic cephalalgias (TACs) and migraine. OBJECTIVES: The aim of the study was to assess whether CASs are also reported by patients with frequent episodic tension-type headache (eTTH). MATERIAL AND METHODS: A cross-sectional online survey of a large Polish population was conducted between August 2021 and June 2022. The analysis assessed diagnostic criteria for migraine and eTTH, as well as the presence of allodynia, headache-related disability and symptoms of depression. RESULTS: The survey involved 3,225 respondents (age: 13-80 years, mean (M) = 38.9 years; 87.1% female). A total of 166 individuals met the diagnostic criteria for isolated frequent eTTH without migraine or probable migraine with or without aura. Allodynia was present during the majority of attacks in 40 (24.1%) eTTH subjects, while 86 (51.8%) eTTH respondents reported at least 1 CAS during their headache attacks. The presence of at least 1 CAS was more prevalent in migraine than in eTTH (p = 0.001). The respondents with at least 1 CAS during eTTH attacks reported a higher burden associated with pain (p = 0.024) and higher Patient Health Questionnaire-9 (PHQ-9) scores (p = 0.016). CONCLUSIONS: The prevalence of retrospectively reported CASs was high among individuals with eTTH, which may potentially contribute to diagnostic errors. Cranial autonomic symptoms in eTTH do not appear to be caused by severe pain or central sensitization.

MuSK Myasthenia Gravis-Potential Pathomechanisms and Treatment Directed against Specific Targets.

Myasthenia gravis (MG) is an autoimmune disease in which autoantibodies target structures within the neuromuscular junction, affecting neuromuscular transmission. Muscle-specific tyrosine kinase receptor-associated MG (MuSK-MG) is a rare, often more severe, subtype of the disease with different pathogenesis and specific clinical features. It is characterized by a more severe clinical course, more frequent complications, and often inadequate response to treatment. Here, we review the current state of knowledge about potential pathomechanisms of the MuSK-MG and their therapeutic implications as well as ongoing research in this field, with reference to key points of immune-mediated processes involved in the background of myasthenia gravis.

The relationship between migraine and Hashimoto's thyroiditis: a single center experience.

Introduction: Hashimoto's thyroiditis (HT) is nowadays the leading cause of hypothyroidism with high and still growing prevalence in general population, but there are lack of data regarding migraine and HT connection. Methods: The aim of this study was to analyze the prevalence of HT in migraine and to check if the presence of HT influence migraine severity. This retrospective observational cohort study involved consecutive migraine patients consulted at our Headache Center with diagnosis of migraine. Electronic charts of patients were collected, including data on migraine type, presence of cranial autonomic symptoms (CAS), monthly migraine days (MMD), medication overuse headache (MOH), and the presence of comorbidities including HT. Results: We found 928 eligible migraine patients, 88.7% were women. The mean age was 36.09 years. 592 (63.8%) were diagnosed with episodic migraine (EM), the rest with chronic migraine (CM). MOH was additionally diagnosed in 258 (27.8%) patients. The duration of migraine was 15.99 years. 106 (11.4%) was diagnosed with HT, 148 (15.9%) with hypothyroidisms, while 84 (9.05%) had both diagnosis. Migraine patients with HT were significantly older (p < 0.001), were more frequently women (p = 0.0017), had longer duration of migraine (p < 0.001), had CAS more frequently (<0.001), developed CM (p = 0.0169) and depression more frequently (p = 0.0047) and had more MMD (p = 0.0195) as compared with individuals without HT. According to our multivariate logistic model, the presence CM was positively associated with HT (OR 1.76, p = 0.045), MOH and duration of migraine, while negatively associated with aura. Conclusion: HT is very prevalent in migraine patients. This is the first study considering migraine and HT to be comorbid and suggesting that HT may influence the course of migraine causing its chronification.

The impact of primary headaches on disability outcomes: a literature review and meta-analysis to inform future iterations of the Global Burden of Disease study.

BACKGROUND: The burden and disability associated with headaches are conceptualized and measured differently at patients' and populations' levels. At the patients' level, through patient-reported outcome measures (PROMs); at population level, through disability weights (DW) and years lived with a disability (YLDs) developed by the Global Burden of Disease Study (GBD). DW are 0-1 coefficients that address health loss and have been defined through lay descriptions. With this literature review, we aimed to provide a comprehensive analysis of disability in headache disorders, and to present a coefficient referring to patients' disability which might inform future GBD definitions of DW for headache disorders. METHODS: We searched SCOPUS and PubMed for papers published between 2015 and 2023 addressing disability in headache disorders. The selected manuscript included a reference to headache frequency and at least one PROM. A meta-analytic approach was carried out to address relevant differences for the most commonly used PROMs (by headache type, tertiles of medication intake, tertiles of females' percentage in the sample, and age). We developed a 0-1 coefficient based on the MIDAS, on the HIT-6, and on MIDAS + HIT-6 which was intended to promote future DW iterations by the GBD consortium. RESULTS: A total of 366 studies, 596 sub-samples, and more than 133,000 single patients were available, mostly referred to cases with migraine. Almost all PROMs showed the ability to differentiate disability severity across conditions and tertiles of medication intake. The indexes we developed can be used to inform future iterations of DW, in particular considering their ability to differentiate across age and tertiles of medication intake. CONCLUSIONS: Our review provides reference values for the most commonly used PROMS and a data-driven coefficient whose main added value is its ability to differentiate across tertiles of age and medication intake which underlie on one side the increased burden due to aging (it is likely connected to the increased impact of common comorbidities), and by the other side the increased burden due to medication consumption, which can be considered as a proxy for headache severity. Both elements should be considered when describing disability of headache disorders at population levels.

Health equity, care access and quality in headache - part 1.

Current definitions of migraine that are based mainly on clinical characteristics do not account for other patient's features such as those related to an impaired quality of life, due to loss of social life and productivity, and the differences related to the geographical distribution of the disease and cultural misconceptions which tend to underestimate migraine as a psychosocial rather than neurobiological disorder.Global differences definition, care access, and health equity for headache disorders, especially migraine are reported in this paper from a collaborative group of the editorial board members of the Journal of Headache and Pain. Other components that affect patients with migraine, in addition to the impact promoted by the migraine symptoms such as stigma and social determinants, are also reported.

The midfacial segment pain: little known disorder in need of scientific evaluation.

Despite its inclusion in the International Classification of Orofacial Pain, tension-type orofacial pain has little support in the scientific literature. However, a similar-in-phenotype orofacial pain perceived in the middle segment of the face has been described by few case series from mostly ear, nose and throat clinics. The authors of these descriptions used the term 'midfacial segment pain'. Patients had no significant sinonasal disorder in these studies, but experienced symmetrical pain perceived mostly over the maxillary and ethmoid sinuses. No aura or autonomic symptoms were present apart from mild nasal congestion or rhinorrhoea in some individuals. This description appears similar to tension-type headache, but with midfacial location. In this viewpoint, we indicate a need to fill this gap in scientific knowledge and propose a multicentre interdisciplinary study that would give a detailed description of this type of orofacial pain.

Real-world effectiveness of fremanezumab in patients with migraine switching from another mAb targeting the CGRP pathway.

This is a summary of the research article entitled "Real-world effectiveness of fremanezumab in patients with migraine switching from another mAb targeting the CGRP pathway: A subgroup analysis of the Finesse Study".The discovery of calcitonin gene-related peptide (CGRP) as a therapeutic target in migraine has been one of the greatest achievements in neurology in recent years. Specific antibodies against CGRP bind to it either via a receptor (erenumab) or ligand (fremanezumab, galcanezumab, eptinezumab). Monoclonal antibodies (mAbs) are effective, safe and welltolerated drugs that have been approved for prophylactic treatment if there are at least 4 days with migraine per month. However, in clinical practice, the failure of treatment with mAbs has been observed, and thus the question arises whether it is worthwhile to include treatment using an antibody with a different mechanism of action.The Finesse Study was designed to evaluate the efficacy of fremanezumab in patients with a history of prior treatment failure with other mAbs against the CGRP pathway. Among the 153 patients with priorly failed mAbs, switching to fremanezumab led to a ≥50% reduction in the number of days with migraine per month in 42.8% of patients. The conclusion emphasizes that switching to another antibody should be considered in patients with prior therapy failure.

Prevalence of headaches and their relationship with obstructive sleep apnea (OSA) - Systematic review and meta-analysis.

Obstructive sleep apnea (OSA) is one of the most common sleep disorders; however, there are inconsistent results about the connection and occurrence of primary and secondary headaches in OSA. Therefore, the primary objectives were to estimate the prevalence and potential relationship between all types of headaches and OSA. A systematic review was conducted according to PRISMA 2020 guidelines. Studies were searched in PubMed, Embase, and Web of science up to July 2023. The Joanna Briggs Institute tool assessed the risk of bias. 1845 articles were identified, and 23 studies describing 15,402 patients were included. Pooled prevalence of all headaches in OSA was 33% (95% CI: 0.25-0.41), 33% for morning headaches (95% CI: 0.24-0.45), 25% for sleep apnea headaches (95% CI: 0.18-0.34), 19% for tension-type headache (95% CI: 0.15-0.23), and 16% for migraine (95% CI: 0.09-0.26). Relative risk for the occurrence of headache in OSA patients compared to the non-OSA people was 1.43 (95% CI: 0.92-2.25). OSA females and males had morning headaches with similar frequency. The prevalence of headaches in OSA was moderate. OSA did not increase the risk of headache. There is a need to conduct further studies focused on bidirectional connections between sleep disorders and headaches.

Health equity, care access and quality in headache - part 2.

BACKGROUND: Headache disorders are a global public health concern affecting diverse populations. This review examines headache service organizations in low-, middle-, and high-income countries. It addresses global challenges in pharmacological headache treatment, with a focus on safety, tolerability, reproductive and child health, and outlines disparities in accessing innovative treatments worldwide. MAIN BODY: Organized headache services are essential due to the wide prevalence and varying severity of headache disorders. The tiered headache service model is globally recognized, although its implementation varies based on financial and workforce considerations. Headache burden affects well-being, causing disability, economic challenges, and work limitations, irrespective of location or income. All nations still require improved diagnosis and treatment, and the majority of countries face obstacles including limited access, awareness, economic barriers, and inadequate health policies. Provided adequate internet availability, telemedicine could help improve health equity by expanding access to headache care, since it can offer patients access to services without lengthy waiting times or extensive travel and can provide healthcare unavailable in underserved areas due to staff shortages. Numerous health disparities restrict global access to many headache medications, especially impacting individuals historically excluded from randomized controlled trials, such as those with cardiovascular and cerebrovascular conditions, as well as pregnant women. Furthermore, despite advancements in researching migraine treatments for young patients, the options for treatment remain limited. Access to headache treatment relies on factors like medication availability, approval, financial coverage, and healthcare provider expertise. Inadequate public awareness leads to neglect by policymakers and undertreatment by patients and healthcare providers. Global access discrepancies are exacerbated by the introduction of novel disease-specific medications, particularly impacting Asian, African, and Latin American nations excluded from clinical trials. While North America and Europe experience broad availability of migraine treatments, the majority of countries worldwide lack access to these therapies. CONCLUSIONS: Healthcare disparities, treatment access, and medication availability are concerning issues in headache medicine. Variations in national healthcare systems impact headache management, and costly innovative drugs are widening these gaps. Healthcare practitioners and experts should acknowledge these challenges and work towards minimizing access barriers for equitable global headache care in the future.

What to do with non-responders to CGRP(r) monoclonal antibodies: switch to another or move to gepants?

In this editorial we aim to provide potential therapeutic options in patients who do not benefit from treatment with CGRP(r) monoclonal antibodies. Based on current real-life studies and analysis of practical and economic aspects, we will analyze the potential benefits of changing CGRP-targeted treatment.

Sinonasal symptoms in migraine without aura: results from the cross-sectional 'Migraine in Poland' study.

Background: Migraine without aura (MwoA) is often mistaken for rhinosinusitis. The purpose of this study was to assess the prevalence of sinonasal symptoms, sinusitis-targeting medication use and burden of migraine in a large group of people with MwoA attacks accompanied by rhinologic symptoms. Methods: Data was collected in a cross-sectional online survey based on an adapted population-based study questionnaire. The analysis included the prevalence of rhinorrhea, mucopurulent nasal discharge, nasal congestion, facial pressure and tenderness to palpation, hyposmia/anosmia and osmophobia. Results: 1,679 (52.73%) MwoA people were identified among 3,225 respondents (women n = 2,809, 87.10%) aged 13-80 years (median age 39; standard deviation 10.4). 1004/1679 (59.8%) migraine patients reported one or more rhinologic symptoms and 341/1679 (20.3%) MwoA respondents had symptoms that met rhinosinusitis clinical diagnostic criteria during their headache attacks. In migraine patients, osmophobia was associated with hyposmia [n = 141 (12.7%) vs. n = 41 (7.2%); p = 0.001] and a sensation of unpleasant smells [n = 216 (19.4%) vs. n = 45 (8.5%); p = 0.001], while facial tenderness to palpation was associated with facial allodynia [n = 532 (50.4%) vs. n = 211 (33.9%); p < 0.001]. People with migraine accompanied by rhinosinusitis-like symptoms experienced more disease burden and used 'sinus medications' more often. Conclusion: MwoA patients with rhinosinusitis-like symptoms during migraine attacks require cautious assessment, especially that some symptoms seem to have little value in distinguishing between these disorders (i.e., facial tenderness, hyposmia), while many of these patients have a greater disease burden and therefore often choose medications targeting rhinologic instead of neurologic mechanisms.

Hereditary Spastic Paraplegia Type 11-Clinical, Genetic and Neuroimaging Characteristics.

Hereditary spastic paraplegia (HSP) is a heterogeneous group of genetically determined diseases, characterised by progressive spastic paraparesis of the lower limbs, associated with degeneration of the corticospinal tract and the posterior column of the spinal cord. HSP occurs worldwide and the estimated prevalence is about 1-10/100,000, depending on the geographic localisation. More than 70 genes responsible for HSP have been identified to date, and reports of new potentially pathogenic variants appear regularly. All possible patterns of inheritance (autosomal dominant, autosomal recessive, X-linked and mitochondrial) have been described in families of HSP patients. Among the autosomal recessive forms of HSP (AR-HSP), hereditary spastic paraplegia type 11 is the most common one. We present a patient with diagnosed HSP 11, with a typical clinical picture and characteristic features in additional diagnostic tests.

Relationship between pain severity, satisfaction with life and the quality of sleep in Polish adults with temporomandibular disorders.

BACKGROUND: Temporomandibular disorders (TMD) pose a serious health problem that can have a negative effect on patients' lives, impair work performance, and result in work absences and restrictions in daily activities. OBJECTIVES: The aim of this observational, cross-sectional study was to evaluate the level of satisfaction with life among Polish patients with TMD and to assess the influence of pain severity on this parameter. A secondary goal was to investigate sleep quality within this patient group and explore its relationship with pain. MATERIAL AND METHODS: A total of 219 patients from the Outpatient Clinic for Temporomandibular Disorders at the University Dental Polyclinic in Wroclaw, Poland, participated in this study. These individuals underwent a clinical examination using the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) protocol and completed 2 validated questionnaires, namely the Satisfaction With Life Scale (SWLS) and the Pittsburgh Sleep Quality Index (PSQI). Furthermore, the patients were assessed for the severity of masseter muscle pain (MMP) and temporal muscle pain (TMP), and the average pain in these muscles (AMP) was calculated. Subsequently, a statistical analysis was performed on the collected data. RESULTS: The group of patients with average satisfaction with life exhibited significantly higher levels of MMP (p = 0.025) and AMP (p = 0.044) as compared to the high-satisfaction group. Regarding sleep quality, 50.23% of the patients experienced poor sleep quality. Poor sleep quality was found to be statistically associated with higher levels of TMP (p = 0.032) and AMP (p = 0.028). Moreover, women demonstrated significantly worse sleep quality as compared to men (p = 0.002). The findings indicate that PSQI has a greater impact on SWLS than vice versa. CONCLUSIONS: Due to a large number of TMD patients experiencing poor sleep quality and the associated reduced life satisfaction, these parameters should be considered as influential factors that modify the management of patients with TMD.

Relationship between alcohol and primary headaches: a systematic review and meta-analysis.

BACKGROUND: Headache is one of the most common neurological symptoms. Many previous studies have indicated a relationship between primary headaches and alcohol. Drinking has been associated with increased risk of tension-type headache (TTH) and migraine. However, recently published studies have not confirmed this relationship. The existing literature is inconclusive; however, migraine patients avoid alcohol. Therefore, the primary objective was to provide a reliable assessment of alcohol intake in people with primary headaches; the secondary objective was to identify any potential relationship between alcohol consumption and headache risk. METHODS: This study was based on PubMed, Embase and Web of Science database searches performed on 11 July 2023. This systematic review was registered in PROSPERO (CRD42023412926). Risk of bias for the included studies was assessed using the Joanna Briggs Institute critical appraisal tools. Meta-analyses were performed using Statistica software. The Risk Ratio (RR) was adopted as the measure of the final effect. Analyses were based on a dichotomous division of the respondents into "non-drinkers" and "drinkers" for headache patients and matched non-headache groups. RESULTS: From a total of 1892 articles, 22 were included in the meta-analysis. The majority demonstrated a moderate or high risk of bias. The first part of the meta-analysis was performed on data obtained from 19 migraine studies with 126 173 participants. The risk of migraine in alcohol drinkers is approximately 1.5 times lower than in the group of non-drinkers (RR = 0.71; 95% CI: 0.57-0.89). The second part involved 9 TTH studies with 28 715 participants. No relationship was found between TTH diagnosis and alcohol consumption (RR = 1.09; 95% CI: 0.93-1.27). Two of the included cluster-headache articles had inconclusive results. CONCLUSIONS: Alcohol consumption and migraine are inversely correlated. The exact mechanism behind this observation may indicate that migraine leads to alcohol-avoidance, rather than alcohol having any protective role against migraine. There was no relationship between TTH and drinking. However, further studies related to primary headaches and alcohol consumption with low risk of bias are required. Additionally, patients and physicians should consider the latest medical data, in order to avoid the myths about alcohol consumption and primary headaches.

Future targets for migraine treatment beyond CGRP.

BACKGROUND: Migraine is a disabling and chronic neurovascular headache disorder. Trigeminal vascular activation and release of calcitonin gene-related peptide (CGRP) play a pivotal role in the pathogenesis of migraine. This knowledge has led to the development of CGRP(-receptor) therapies. Yet, a substantial proportion of patients do not respond to these treatments. Therefore, alternative targets for future therapies are warranted. The current narrative review provides a comprehensive overview of the pathophysiological role of these possible non-CGRP targets in migraine. FINDINGS: We covered targets of the metabotropic receptors (pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP), amylin, and adrenomedullin), intracellular targets (nitric oxide (NO), phosphodiesterase-3 (PDE3) and -5 (PDE5)), and ion channels (potassium, calcium, transient receptor potential (TRP), and acid-sensing ion channels (ASIC)). The majority of non-CGRP targets were able to induce migraine-like attacks, except for (i) calcium channels, as it is not yet possible to directly target channels to elucidate their precise involvement in migraine; (ii) TRP channels, activation of which can induce non-migraine headache; and (iii) ASICs, as their potential in inducing migraine attacks has not been investigated thus far. Drugs that target its receptors exist for PACAP, NO, and the potassium, TRP, and ASIC channels. No selective drugs exist for the other targets, however, some existing (migraine) treatments appear to indirectly antagonize responses to amylin, adrenomedullin, and calcium channels. Drugs against PACAP, NO, potassium channels, TRP channels, and only a PAC1 antibody have been tested for migraine treatment, albeit with ambiguous results. CONCLUSION: While current research on these non-CGRP drug targets has not yet led to the development of efficacious therapies, human provocation studies using these targets have provided valuable insight into underlying mechanisms of migraine headaches and auras. Further studies are needed on these alternative therapies in non-responders of CGRP(-receptor) targeted therapies with the ultimate aim to pave the way towards a headache-free future for all migraine patients.

Migraine symptoms, healthcare resources utilization and disease burden in a large Polish migraine cohort : Results from 'Migraine in Poland'-a nationwide cross-sectional survey.

BACKGROUND: The Migraine in Poland study is the first large scale nationwide cross-sectional online survey of symptoms, approaches to management, treatment patterns, quality of life, and sociodemographic characteristics of the Polish migraine patients' cohort, conducted from August 2021 to June 2022. METHODS: A cross-sectional online survey was designed based on the American Migraine Prevalence and Prevention (AMPP) Study. Participants were recruited through broad advertisement through various channels. The survey included questions allowing for the diagnosis of migraine without aura (MwoA) based on the third edition of the International Classification of Headache Disorders (ICHD-3). Moreover, the questionnaire assessed sociodemographic and headache features, comorbidities, consultation rates with medical professionals, as well as the use of abortive or preventive treatment, including non-pharmacological methods, psychological symptoms and the burden of migraine. RESULTS: A structured online questionnaire was submitted by 3225 respondents aged 13 to 80 (mean age 38.9, 87.1% women). In this group 1679 (52.7%) of participants fulfilled ICHD-3 diagnostic criteria for MwoA, which was in most cases (88.3%) confirmed by a medical professional in the past. In this group the average number of monthly headache days was 4.7, while 47.8% of participants had at least 4 migraine days per month. Mean Migraine Disability Assessment score was 42.65 (median 32). Among MwoA respondents, 1571 (93.6%) had consulted their headache with a medical professional in the past - mostly neurologists (n = 1450 (83.4%) and primary care physicians (n = 1393 (82.9%). In the MwoA cohort, 1553 (92.5%) of participants declared the current use of some form of treatment, although only 193 (11.5%) respondents were currently on preventive medications. The most prevalent comorbidities included: chronic rhinitis (37.1%), allergies (35.9%) and low blood pressure (26.9%). Anxiety (20.4%) and depression (21.3%) were highly prevalent among participants. CONCLUSIONS: People with migraine in Poland face similar difficulties as their peers in other countries. Despite relatively high access to neurologist consultations and good diagnosis accuracy, migraine still poses diagnostic and therapeutic difficulties. In this context, migraine undertreatment in Polish population must be underlined, especially in context of high disease burden.

Efficiency of occlusal splint therapy on orofacial muscle pain reduction: a systematic review.

BACKGROUND: This systematic review aims to examine the existing original studies to determine the effectiveness of occlusal splints (OSs) in the management of orofacial myalgia and myofascial pain (MP) in comparison with no treatment or other interventions. MATERIALS AND METHODS: Based on the inclusion and exclusion criteria of this systematic review, randomized controlled trials were qualified, in which the effectiveness of occlusal splint therapy in the management of muscle pain was examined in comparison with no treatment or other interventions. This systematic review was conducted according to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020. The authors searched three databases (PubMed, CINAHL (The Cumulative Index to Nursing and Allied Health Literature) and Scopus) for English publications published between January 1, 2010, and June 1, 2022. The last database search was carried out on June 4, 2022. Data were extracted from the included studies and assessed for risk of bias using the revised Cochrane risk-of-bias tool for randomized trials. RESULTS: Thirteen studies were identified for inclusion in this review. In total, 589 patients were diagnosed with orofacial muscle pain who underwent education and various forms of therapy including different types of OSs, light emitting diode therapy, acupuncture, low-level laser therapy, device-supported sensorimotor training, Kinesio Taping, myofunctional therapy, and physical therapy. All studies included demonstrated a high risk of bias. CONCLUSIONS: There is insufficient evidence regarding whether OS therapy in the treatment of orofacial myalgia and MP offers an advantage over other forms of interventions or no treatment. Further reliable clinical studies in this area are needed to improve the quality of research, which should be performed with larger groups of blinded respondents and controls. CLINICAL RELEVANCE: Due to the large-scale nature of orofacial muscle pain, it is assumed that each dental clinician will meet patients with orofacial muscle pain repeatedly in daily practice; hence, the review of the effectiveness of OSs in the management of orofacial myalgia and MP is necessary.

The sense of stopping migraine prophylaxis.

INTRODUCTION: Migraine prophylactic therapy has changed over recent years with the development and approval of monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway. As new therapies emerged, leading headache societies have been providing guidelines on the initiation and escalation of such therapies. However, there is a lack of robust evidence looking at the duration of successful prophylaxis and the effects of therapy discontinuation. In this narrative review we explore both the biological and clinical rationale for prophylactic therapy discontinuation to provide a basis for clinical decision-making. METHODS: Three different literature search strategies were conducted for this narrative review. These include i) stopping rules in comorbidities of migraine in which overlapping preventives are prescribed, notably depression and epilepsy; ii) stopping rules of oral treatment and botox; iii) stopping rules of antibodies targeting the CGRP (receptor). Keywords were utilized in the following databases: Embase, Medline ALL, Web of Science Core collection, Cochran Central Register of Controlled Trials, and Google Scholar. DISCUSSION: Reasons to guide decision-making in stopping prophylactic migraine therapies include adverse events, efficacy failure, drug holiday following long-term administration, and patient-specific reasons. Certain guidelines contain both positive and negative stopping rules. Following withdrawal of migraine prophylaxis, migraine burden may return to pre-treatment level, remain unchanged, or lie somewhere in-between. The current suggestion to discontinue CGRP(-receptor) targeted mAbs after 6 to 12 months is based on expert opinion, as opposed to robust scientific evidence. Current guidelines advise the clinician to assess the success of CGRP(-receptor) targeted mAbs after three months. Based on excellent tolerability data and the absence of scientific data, we propose if no other reasons apply, to stop the use of mAbs when the number of migraine days decreases to four or fewer migraine days per month. There is a higher likelihood of developing side effects with oral migraine preventatives, and so we suggest stopping these drugs according to the national guidelines if they are well tolerated. CONCLUSION: Translational and basic studies are warranted to investigate the long-term effects of a preventive drug after its discontinuation, starting from what is known about the biology of migraine. In addition, observational studies and, eventually, clinical trials focusing on the effect of discontinuation of migraine prophylactic therapies, are essential to substantiate evidence-based recommendations on stopping rules for both oral preventives and CGRP(-receptor) targeted therapies in migraine.

Genetics of migraine: where are we now?

Migraine is a complex brain disorder explained by the interaction of genetic and environmental factors. In monogenic migraines, including familial hemiplegic migraine and migraine with aura associated with hereditary small-vessel disorders, the identified genes code for proteins expressed in neurons, glial cells, or vessels, all of which increase susceptibility to cortical spreading depression. The study of monogenic migraines has shown that the neurovascular unit plays a prominent role in migraine. Genome-wide association studies have identified numerous susceptibility variants that each result in only a small increase in overall migraine risk. The more than 180 known variants belong to several complex networks of "pro-migraine" molecular abnormalities, which are mainly neuronal or vascular. Genetics has also highlighted the importance of shared genetic factors between migraine and its major co-morbidities, including depression and high blood pressure. Further studies are still needed to map all of the susceptibility loci for migraine and then to understand how these genomic variants lead to migraine cell phenotypes.