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.

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.

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 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.

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.

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.

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.

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.

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.

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.

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.

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.

Primary headache epidemiology in children and adolescents: a systematic review and meta-analysis.

INTRODUCTION: Headache is the most prevalent neurological manifestation in adults and one of the leading causes of disability worldwide. In children and adolescents, headaches are arguably responsible for a remarkable impact on physical and psychological issues, yet high-quality evidence is scarce. MATERIAL AND METHODS: We searched cross-sectional and cohort studies in Embase, Medline, Web of Science, and Cochrane databases from January 1988 to June 2022 to identify the prevalence of headaches in 8-18 years old individuals. The risk of bias was examined with the Joanna Briggs Institute (JBI) scale. A random-effects model was used to estimate the pooled prevalence of pediatric headache. Subgroup analyses based on headache subtypes were also conducted. RESULTS: Out of 5,486 papers retrieved electronically, we identified 48 studies that fulfilled our inclusion criteria. The pooled prevalence of primary headaches was 11% for migraine overall [95%CI: 9-14%], 8% for migraine without aura (MwoA) [95%CI: 5-12%], 3% for migraine with aura (MwA) [95%CI:2-4%] and 17% for tension-type headache (TTH) [95% CI: 12-23%]. The pooled prevalence of overall primary headache in children and adolescents was 62% [95% CI: 53-70%], with prevalence in females and males of 38% [95% CI: 16-66%] and 27% [95% CI: 11-53%] respectively. After the removal of studies ranked as low-quality according to the JBI scale, prevalence rates were not substantially different. Epidemiological data on less common primary headaches, such as trigeminal autonomic cephalalgias, were lacking. CONCLUSION: We found an overall remarkably high prevalence of primary headaches in children and adolescents, even if flawed by a high degree of heterogeneity. Further up-to-date studies are warranted to complete the picture of pediatric headache-related burden to enhance specific public interventions.

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.

COVID-19-related headache and innate immune response - a narrative review.

Headache is one of the most prevalent, although often underreported, symptoms of coronavirus disease 2019 (COVID-19). It is generally accepted that this symptom is a form of secondary headache due to systemic viral infection. There are several hypotheses that try to explain its aetiopathogenesis. One of the most compelling is related to innate immune response to viral infection. This rationale is supported by similarities to other viral infections and the temporal overlap between immunological reactions and headache. Moreover, several key factors in innate immunity have been shown to facilitate headache e.g. interferons, interleukin (IL) -1-ß, IL-6, and tumour necrosis factor. There is also a possibility that the virus causes headache by the direct activation of afferents through pattern recognition receptors (i.e. Toll-like receptor 7). Moreover, some data on post-COVID-19 headache and after vaccination against SARS-CoV-2 infection suggests a similar cytokine-mediated pathomechanism in these clinical situations. Future research should look for evidence of causality between particular immune response factors and headache. Identifying key molecules responsible for headache during acute viral infection would be an important step towards managing one of the most prevalent secondary headache disorders.

COVID-19-related headache and sinonasal inflammation: A longitudinal study analysing the role of acute rhinosinusitis and ICHD-3 classification difficulties in SARS-CoV-2 infection.

BACKGROUND: The genesis of headache in coronavirus disease 2019 (COVID-19) is currently unclear and the multitude of disease symptoms often further hinders locating the source of pain. Interestingly, many subjects with COVID-19 have symptoms of acute rhinosinusitis. The relation between nasal symptoms and headache in SARS-CoV-2 infection remains unknown. METHODS: This bi-center longitudinal study evaluated symptoms in consecutive COVID-19 patients in the participating practices. The first assessment was performed during the initial consultation after infection confirmation. That was followed up by a second consultation after a median 9 days. RESULTS: 130 patients were included in the study (80 women, 50 men; mean age 46.9 years). Headache was highly prevalent at the first visit (72%) and significantly associated with acute rhinosinusitis symptoms. The odds ratio for headache in subjects with rhinosinusitis was 3.5. Headache could be attributed to systemic viral infection in 96% and to acute rhinosinusitis in 51% of cases according to 3rd edition of the International Classification of Headache Disorders. Criterium C.3 (exacerbation of headache by pressure applied over paranasal sinuses) and C.4 (ipsilaterality of headache and sinusitis) had low sensitivity in headache attributed to acute rhinosinusitis. CONCLUSIONS: Nasal inflammation is associated with headache in COVID-19, although the pain mechanism lies probably in a systemic reaction to the virus. 3rd edition of the International Classification of Headache Disorders criteria for headache attributed to acute rhinosinusitis need adjusting to the current understanding of acute sinonasal infection.

Headache onset after vaccination against SARS-CoV-2: a systematic literature review and meta-analysis.

BACKGROUND: Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are used to reduce the risk of developing Coronavirus Disease 2019 (COVID-19). Despite the significant benefits in terms of reduced risk of hospitalization and death, different adverse events may present after vaccination: among them, headache is one of the most common, but nowadays there is no summary presentation of its incidence and no description of its main features. METHODS: We searched PubMed and EMBASE covering the period between January 1st 2020 and August 6th, 2021, looking for record in English and with an abstract and using three main search terms (with specific variations): COVID-19/SARS-CoV-2; Vaccination; headache/adverse events. We selected manuscript including information on subjects developing headache after injection, and such information had to be derived from a structured form (i.e. no free reporting). Pooled estimates and 95% confidence intervals were calculated. Analyses were carried out by vaccine vs. placebo, by first vs. second dose, and by mRNA-based vs. "traditional" vaccines; finally, we addressed the impact of age and gender on post-vaccine headache onset. RESULTS: Out of 9338 records, 84 papers were included in the review, accounting for 1.57 million participants, 94% of whom received BNT162b2 or ChAdOx1. Headache was generally the third most common AE: it was detected in 22% (95% CI 18-27%) of subjects after the first dose of vaccine and in 29% (95% CI 23-35%) after the second, with an extreme heterogeneity. Those receiving placebo reported headache in 10-12% of cases. No differences were detected across different vaccines or by mRNA-based vs. "traditional" ones. None of the studies reported information on headache features. A lower prevalence of headache after the first injection of BNT162b2 among older participants was shown. CONCLUSIONS: Our results show that vaccines are associated to a two-fold risk of developing headache within 7 days from injection, and the lack of difference between vaccine types enable to hypothesize that headache is secondary to systemic immunological reaction than to a vaccine-type specific reaction. Some descriptions report onset within the first 24 h and that in around one-third of the cases, headache has migraine-like features with pulsating quality, phono and photophobia; in 40-60% of the cases aggravation with activity is observed. The majority of patients used some medication to treat headache, the one perceived as the most effective being acetylsalicylic acid.

Neuromyelitis Optica Spectrum Disorder Treatment-Current and Future Prospects.

Neuromyelitis optica (NMO) is an immune-mediated demyelinative disorder of the central nervous system affecting mainly the optical nerves and the spinal cord. The recurrent course of the disease, with exacerbations and incomplete remissions, causes accumulating disability, which has a profound impact upon patients' quality of life. The discovery of antibodies against aquaporin 4 (AQP4) and their leading role in NMO etiology and the formulation of diagnostic criteria have improved appropriate recognition of the disease. In recent years, there has been rapid progress in understanding the background of NMO, leading to an increasing range of treatment options. On the basis of a review of the relevant literature, the authors present currently available therapeutic strategies for NMO as well as ongoing research in this field, with reference to key points of immune-mediated processes involved in the background of the disease.

Migraine and Sleep-An Unexplained Association?

Migraine and sleep disorders are common chronic diseases in the general population, with significant negative social and economic impacts. The association between both of these phenomena has been observed by clinicians for years and is confirmed by many epidemiological studies. Despite this, the nature of this relationship is still not fully understood. In recent years, there has been rapid progress in understanding the common anatomical structures of and pathogenetic mechanism between sleep and migraine. Based on a literature review, the authors present the current view on this topic as well as ongoing research in this field, with reference to the key points of the biochemical and neurophysiological processes responsible for both these disorders. In the future, a better understanding of these mechanisms will significantly expand the range of treatment options.

Pathophysiology of the Different Clinical Phenotypes of Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP).

Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common form of autoimmune polyneuropathy. It is a chronic disease and may be monophasic, progressive or recurrent with exacerbations and incomplete remissions, causing accumulating disability. In recent years, there has been rapid progress in understanding the background of CIDP, which allowed us to distinguish specific phenotypes of this disease. This in turn allowed us to better understand the mechanism of response or non-response to various forms of therapy. On the basis of a review of the relevant literature, the authors present the current state of knowledge concerning the pathophysiology of the different clinical phenotypes of CIDP as well as ongoing research in this field, with reference to key points of immune-mediated processes involved in the background of CIDP.