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Introduction: The discovery of the role of the calcitonin gene-related peptide (CGPR) in migraine pathogenesis ushered in a new era in headache medicine. This evidence led to the development of small-molecule CGRP receptor antagonists and monoclonal antibodies targeting either CGRP or its receptor., Areas Covered: We will present selected aspects of the role of CGRP in the pathogenesis of migraine, the efficacy of CGRP-targeted treatment, and the still-open questions regarding the practical application of CGRP antagonists in headache medicine., Expert Opinion: CGRP-targeting drugs represent a transformative approach to migraine treatment, offering superior efficacy and tolerability compared to traditional therapies, they are a helpful addition to the treatment arsenal but also have their flaws and require further observation. Their availability provides new hope for migraine patients, particularly those who have not responded adequately to conventional treatments. Future directions for migraine care planning, especially for chronic migraine and medication-overuse headache, should include universal access to these specific and effective forms of therapy to prevent complications from the disease and its negative effects in many aspects of a patient's life.

Introduction: Upper respiratory tract infections (URTIs) are among the most common reasons for patients consulting a general practitioner (GP) during the infectious diseases season, with viruses being the predominant cause. The COVID-19 pandemic has significantly impacted GPs' perception of these infections. The pandemic's progression, especially with the emergence of the Omicron variant, has complicated the diagnosis and treatment of URTIs, with evolving symptoms., Aim: The aim of this study was to assess the differences in symptoms reported by patients with various infections, such as COVID-19, influenza, common cold, and post-viral rhinosinusitis, during the infectious diseases season of November 2023 to March 2024., Materials and Methods: The study was conducted in a primary health care clinic, providing care for a population of approximately 10,000 people, among adult patients presenting with URTI symptoms during the 2023/2024 infectious diseases season. Patients qualified for the study were swabbed for SARS-CoV-2, influenza A and B and respiratory syncytial virus (RSV) antigens. Symptoms were assessed with the use of a semi-structured questionnaire., Results: Of the 1810 patients presenting with symptoms of URTIs, 276 patients were included in the study. Among patients with COVID-19, symptoms of nasal obstruction ( p  = 0.005) and nasal discharge ( p  = 0.001) were less common than in those with influenza or common cold. However, these nasal symptoms were significantly more frequent among patients with COVID-19 who had confirmed previous immunization (COVID-19 history or vaccination) ( p  = 0.028)., Conclusion: The incidence of individual sinonasal symptoms varies significantly depending on the aetiological agent of the URTI. This observation may not only help clinicians make the correct diagnosis, but also suggests an inflammatory response in the nasal mucosa and paranasal sinuses that is dependent on the aetiological agent. The study also indicates that this response is altered within the same virus species following immunization., Limitations: The study's limitations include a small sample size (276 patients), focus on one season and one GP practice, and reliance on clinical signs and antigen tests. Nonetheless, the findings provide valuable insights. Further research with larger patient groups and extended follow-up periods is required to confirm these findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Straburzyński and Romaszko-Wojtowicz.)

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.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Nowaczewska, Straburzyński, Meder and Waliszewska-Prosół.)

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., Competing Interests: Declaration of competing interest All authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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., Competing Interests: Declaration of conflicting interestsThe authors declare that there are no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Aim of Study: This study aimed to compare headache and facial pain prevalence and headache phenotype among people with common upper respiratory tract infections (URTIs)., Clinical Rationale for Study: Headache is a common symptom in viral URTI, but its phenotyping has so far been limited to coronavirus disease 2019 (COVID-19) and influenza. Additionally, the prevalence of facial pain in URTIs has only rarely been discussed in scientific publications., Material and Methods: Patients with acute URTI symptoms were evaluated for headache phenotype using a semi-structured questionnaire. Antigen swab tests were performed in all participants., Results: The analysis included 276 URTI/APVRS (acute post-viral rhinosinusitis) episodes in 223 patients (136 women, 60.1%) aged 18-73 [mean 41.3 / median (25th, 75th) 40 / standard deviation 15.1]. Participants were diagnosed with: COVID-19 - 107/276 (38.8%); 'common cold' - 103/276 (37.3%); influenza - 36/276 (13.0%); or APVRS - 30/276 (10.9%). Headache was present in 183/276 (66.3%) and URTIs and facial pain in 107/276 (38.8%). Predictors of headache in URTIs included sinonasal symptoms (odds ratio (OR) 10.70, p < 0.001) and fever (OR 2.9, p = 0.004). Headache more often (p = 0.030) had a migraine-like phenotype in COVID-19 (27.4% (20/73) vs. 9.1% (10/110) and tension-type headache (TTH)-like phenotype in 'common cold' (75.4%, 49/64 vs. 61.3%, 73/119). Previous COVID-19 immunisation (vaccination or infection) was associated (p = 0.004) with a lower prevalence of migraine-like headache [6.3% (1/16) vs. 32.8% (19/58)]., Conclusions and Clinical Implications: Headache and facial pain are prevalent during URTIs, and are associated with general and sinonasal immune response rather than virus type. Headache phenotype may depend on the causative microorganism, but it can evolve in response to previous immunisation. Our study supports vaccination against COVID-19, as people with prior immunisation are probably less likely to experience migraine-like headache.

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., (© 2023. Springer-Verlag Italia S.r.l., part of Springer Nature.)

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., (© 2023. The Author(s).)

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-β, 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.

Background: Acute rhinosinusitis (ARS) is a common and well-defined disorder, primarily of viral aetiology, with rhinovirus and coronavirus accounting for more than 50% of viral ARS. The fight with COVID-19 pandemic resulted in an increased availability viral testing, which in turn allowed testing for presence of SARS-Cov-2 in all patients presenting common cold (or ARS) symptoms. The aim of this study was to assess the clinical characteristics of acute rhinosinusitis in patients diagnosed with COVID-19., Methodology/principal: This study is a post-hoc analysis. Patients symptoms were evaluated using a structured questionnaire twice: directly after a positive SARS-Cov-2 result and 7-12 days following the first evaluation. Subjects were asked about presence of nasal and systemic symptoms as well as headache., Results: A total of 130 COVID-19 symptomatic patients were recruited into the study, 58 (45%) patients met EPOS2020 diagnostic criteria for ARS. Of all ARS patients, 72% presented with rhinorrhoea, 69% with pain perceived over paranasal sinuses, 62% with nasal congestion, 52% with cough, 45% with olfactory dysfunction, 38% with fever, 33% with facial pressure and in 22% pain was exacerbated by sinus palpation., Conclusions: Half of COVID-19 subjects has ARS. The course of SARS-Cov-2 ARS does not seem to differ significantly from ARS of other aetiologies. Since ARS in the course of COVID-19 seems to meet the definition of ARS proposed by EPOS 2020, we hypothesize that substances validated for ARS treatment, such as intranasal corticosteroids could be effective in SARS-Cov-2 ARS.

The identification of patients who can benefit the most from the available preventive treatments is important in chronic migraine. We explored the rate of excellent responders to onabotulinumtoxinA in a multicenter European study and explored the predictors of such response, according to different definitions. A pooled analysis on chronic migraineurs treated with onabotulinumtoxinA and followed-up for, at least, 9 months was performed. Excellent responders were defined either as patients with a ≥75% decrease in monthly headache days (percent-based excellent responders) or as patients with <4 monthly headache days (frequency-based excellent responders). The characteristics of excellent responders at the baseline were compared with the ones of patients with a <30% decrease in monthly headache days. Percent-based excellent responders represented about 10% of the sample, whilst frequency-based excellent responders were about 5% of the sample. Compared with non-responders, percent-based excellent responders had a higher prevalence of medication overuse and a higher excellent response rate even after the 1st and the 2nd injection. Females were less like to be frequency-based excellent responders. Chronic migraine sufferers without medication overuse and of female sex may find fewer benefits with onabotulinumtoxinA. Additionally, the excellent response status is identifiable after the first cycle.

Introduction: Monoclonal antibodies (mAbs) showed efficacy in migraine prevention. The aim of this study was to check if baseline clinical parameters and cerebral blood flow (CBF) measured by transcranial Doppler (TCD) may help predict mAbs efficacy., Methods: Electronic charts of migraineurs treated with erenumab or fremanezumab, with baseline TCD evaluations were collected, including data on migraine type, pain localization, monthly migraine days (MMD), medication overuse headache (MOH), mean blood flow velocity (Vm), and pulsatility index (PI) in cerebral arteries., Results: A total of 123 patients were enrolled, mean age 38, 75 years, 87 with chronic migraine, 61 with MOH, 72 were good responders (GR), and reported ≥50% reduction in MMD, 43 ≥75% reduction in MMD. Baseline Vm values in MCAs were significantly lower in GR as compared with non-responders. MAbs responsiveness ≥50% was positively associated with unilateral pain localization (OR: 6.53, 95% CI: 2.01-23.93; p = 0.003) and HIT-6 score (OR: 1.14, 95% CI: 1.01-1.30; p = 0.036) whereas negatively associated with Vm in right MCA (OR: 0.96, 95% CI: 0.92-0.99; p = 0.012), and having no relatives with migraine (OR: 0.40, 95% CI: 0.16-0.95; p = 0.040)., Conclusions: Baseline Vm in MCA is lower in mAbs GR as compared with non-responders which may reflect increased secretion of CGRP with further vasodilation in GR. Simple clinical features and baseline CBF in anterior circulation might help to predict the patient's responsiveness., Competing Interests: MN and MS have received lecture honoraria from Novartis Poland Sp. z o.o. and Teva Pharmaceuticals Polska Sp. z o.o. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nowaczewska, Straburzyński, Waliszewska-Prosół, Meder, Janiak-Kiszka and Kaźmierczak.)

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 1 st 2020 and August 6 th , 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., (© 2022. The Author(s).)

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.