Unsatisfactory response to acute medications does not affect the medication overuse headache development in pediatric chronic migraine.

BACKGROUND: Chronic migraine (CM) negatively impacts the quality of life of 2 to 4% of pediatric patients. In adults, CM is frequently linked to medication overuse headache (MOH), but there is a much lower prevalence of MOH in children. A suboptimal response to acute therapies may lead to their reduced use, thus preventing MOH development in children and adolescents. The frequency of patients with CM who do not respond to acute therapies was examined in the present study. We investigated whether the prevalence of MOH was different between responders and non-responders. We also examined whether patients receiving prophylactic therapy had an improved response to acute therapy. Finally, we investigated if there was a difference in the frequency of psychiatric comorbidities between responders and non-responders. METHODS: We retrospectively analysed clinical data of all chronic pediatric migraineurs under the age of 18 referred to the Headache Centre at Bambino Gesù Children Hospital in June 2021 and February 2023. ICHD3 criteria were used to diagnose CM and MOH. We collected demographic data, including the age at onset of migraine and the age of the CM course. At baseline and after 3 months of preventive treatment, we evaluated the response to acute medications. Neuropsychiatric comorbidities were referred by the children's parents during the first attendance evaluation. RESULTS: Seventy patients with CM were assessed during the chosen period. Paracetamol was tried by 41 patients (58.5%), NSAIDs by 56 patients (80.0%), and triptans by 1 patient (1.4%). Fifty-one participants (73%) were non-responder to the abortive treatment. The presence of MOH was detected in 27.1% of the whole populations. Regarding our primary aim, MOH was diagnosed in 29% of non-responder patients and 22% of responders (p > 0.05). All patients received preventative treatment. After 3 months of preventive pharmacological therapy, 65.4% of patients who did not respond to acute medications achieved a response, while 34.6% of patients who were non-responder remain non-responder (p < 0.05). Prophylactic therapy was also effective in 69% of patients who responded to acute medication (p < 0.05). Psychiatric comorbidities were detected in 68.6% of patients, with no difference between responders and non-responders (72.2% vs. 67.3%; p = 0.05). CONCLUSIONS: Despite the high prevalence of unresponsiveness to acute therapies in pediatric CM, it does not act as a protective factor for MOH. Moreover, responsiveness to acute drugs is improved by pharmacological preventive treatment and it is not affected by concomitant psychiatric comorbidities.

Sleep disturbances and behavioral symptoms in pediatric Sotos syndrome.

Background: Sotos syndrome (SoS) is a rare overgrowth genetic disease caused by intragenic mutations or microdeletions of the NSD1 gene located on chromosome 5q35. SoS population might present cognitive impairment and a spectrum of behavioral characteristics, with a worse profile in patients with microdeletion. Although patients with SoS are known to have impaired sleep habits, very little data are available. The present study aimed to assess the prevalence of sleep disorders (SDs) in a pediatric cohort of patients with SoS and their correlation with neuropsychiatric profiles. Methods: We included patients with a SoS diagnosis and age < 18 years; all patients underwent a comprehensive neuropsychological assessment, including evaluation of cognition, adaptive functions through the Adaptive Behavior Assessment System-Second Edition (ABAS-II), and behavioral problems using the Achenbach Child Behavior Checklist (CBCL) and Conners' Parent Rating Scale-Revised (CPRS-R:L) questionnaire. To investigate the presence of SD parents, the Sleep Disturbance Scale for Children (SDSC) was completed. Results: Thirty-eight patients (M 61%, F 39%, mean age 11.1 ± 4.65 years) were included in the study. Although only two had a prior SD diagnosis, 71.1% (N = 27) exhibited pathological scores on SDSC. No statistically significant associations were found between positive SDSC results and genetic microdeletion, intellectual disability (ID), or other medical conditions/treatments. However, a positive correlation emerged between SDSC scores and Conners' Global Index (p = 0.048) and Restless/Impulsive (p = 0.01) scores, CBCL externalizing (p = 0.02), internalizing (p = 0.01), and total scores (p = 0.05). Conversely, a negative linear relationship was observed between the SDSC score and the ABAS GAC and ABAS CAD scores (p = 0.025). Conclusion: We detected an SD in 71.1% of our sample, with a positive relation between SD and internalizing and externalizing symptom levels, especially hyperactivity and impulsivity. Our study demonstrated a high prevalence of SD in pediatric patients with SoS, highlighting that all patients should be screened for this problem, which has a great impact on the quality of life of patients and their families.

Short report: Autistic symptoms in Sotos syndrome, preliminary results from a case-control study.

BACKGROUND: An extremely heterogeneous neuropsychological phenotype has been reported in Sotos Syndrome (SoS), including socio-communicative and behavioral difficulties referred to Autism Spectrum Disorder (ASD). Nonetheless, to date, only few data are available on the topic. AIM: To investigate ASD symptoms within a sample of children with SoS in comparison to a matched control group of individuals with idiopathic ASD. METHODS: A convenience sample of SoS (n = 33, age: 9.8 ± 4.1) and ASD (n = 33, age: 9.9 ± 4.1), was included. Autistic symptoms' assessment was performed through the administration of the Autism Diagnostic Observation Schedule-Second Edition- ADOS-2, the Social Responsiveness Scale -SRS and the Social Communication Questionnaire-SCQ. RESULTS: 72.7% of SoS children presented mild to moderate levels of ASD symptoms as measured by the ADOS-2. Oneway ANOVA analysis showed that SoS individuals presenting lower IQ demonstrated higher ASD symptom's level (p = 0.01). No statistically significant differences emerged between the SoS and ASD groups within the SRS total score domain (p = 0.95). CONCLUSIONS AND IMPLICATIONS: Our results support the evidence for an increased risk for ASD in SoS, suggesting that the ASD symptoms' assessment should be regularly performed in SoS children, with subsequent important implications in terms of therapeutic strategies and later outcome.

White matter hyperintensities in migraine are not mediated by a dysfunction of the glymphatic system-A diffusion tensor imaging magnetic resonance imaging study.

OBJECTIVE: We assessed whether brain magnetic resonance imaging (MRI) markers of glymphatic function are altered in patients with migraine and brain white matter hyperintensities (WMHs). BACKGROUND: The glymphatic system is responsible for the outflow of waste products from the brain. An impaired glymphatic system has been associated with WMH; however, this impairment has not been shown in patients with migraine. METHODS: The present cross-sectional study included consecutive patients with migraine from a single tertiary headache center. Glymphatic function was assessed by measuring the diffusion tensor imaging along the perivascular space (DTI-ALPS) technique, resulting in an index value. WMHs were assessed and quantified by using the Scheltens semi-quantitative score. RESULTS: We included 147 patients (120 women [81.6%]) with a median (interquartile range [IQR]) age of 45 (36-50) years. In all, 74 (50.3%) patients had WMHs. The median (IQR) ALPS index was similar in patients with WMHs compared with those without, at 2.658 (2.332-3.199) versus 2.563 (2.222-3.050) (p = 0.344). The Scheltens score did not correlate with ALPS index (rho = 0.112, p = 0.268). CONCLUSIONS: Our results suggest that the presence of WMHs is not associated with an impairment in the glymphatic system in patients with migraine. Although negative and worthy of further confirmation, our finding has implications for the understanding of the nature of WMH in patients with migraine.

Cognitive, adaptive and behavioral profile in Sotos syndrome children with 5q35 microdeletion or intragenic variants.

Sotos syndrome (SoS) is a congenital overgrowth syndrome with variable degree of intellectual disability caused in the 90% of cases by pathogenetic variants of the Nuclear receptor binding SET Domain protein1 (NSD1) gene. NSD1 gene functions can be abrogated by different genetic alterations (i.e., small intragenic pathogenic variants like deletions/insertions, nonsense/missense pathogenic variants, partial gene deletions and whole deletions or microdeletion of 5q35 chromosomal region). Therefore, correlation of the genotype-phenotype with a possible contribution of more implicated genes to the medical, cognitive and behavioral profile is a topic of great interest. Although a more severe learning disability has been described in individuals with 5q35 microdeletion when compared to individuals with NSD1 intragenic pathogenic variants a fully delineated cognitive and behavioral phenotype has not been described yet. The importance of providing clinical characterization in relation to the genotype comes from the necessity to early identify children more at risk of developing psychopathological disorders. We characterize the cognitive, adaptive and behavioral phenotype of a pediatric sample of 64 individuals affected by SoS, performing a standardized neuropsychological evaluation. Secondly, we compare cognitive-behavioral profiles of SoS individuals carrying and not carrying the 5q35 microdeletion. SoS participants were characterized by a mild cognitive impairment of both Intellectual Quotient and adaptive skills in association to borderline symptoms of attention deficit. Our results suggest that the 5q35 microdeletion is associated with lower scores specifically concerning the cognitive, adaptive functioning and behavioral domains. However, longitudinal studies are necessary to confirm these findings and delineate a developmental trajectory of SoS.

Visual Disturbances Spectrum in Pediatric Migraine.

Migraine is a complex neurological disorder with partially unknown pathophysiological mechanisms. The prevalence in childhood ranges from 7.7% to 17.8%, thus representing the most frequent primary headache. In half of the cases, migraine is accompanied or preceded by various neurological disturbances, among which the visual aura is the best known. In literature, other conditions, such as Alice in Wonderland Syndrome and Visual Snow syndrome, are characterized by visual manifestations and are often associated with migraine. The aim of this narrative review is to describe the spectrum of visual disturbances in pediatric migraine and their pathophysiological mechanisms.

Real Life Data on OnabotulinumtoxinA for Treatment of Chronic Migraine in Pediatric Age.

BACKGROUND: The use of OnabotulinumtoxinA (OBT-A) for the treatment of chronic migraine (CM) in adults represents a therapy with the greatest efficacy and safety data. However, we have little evidence on the use of OBT-A in children or adolescents. The present study aims to describe the experience with OBT-A in the treatment of CM in adolescents in an Italian third-level headache center. METHODS: The analysis included all patients under the age of 18 treated with OBT-A for CM at the Bambino Gesù Children's Hospital. All patients received OBT-A following the PREEMPT protocol. Subjects were classified as good responders if a greater than 50% reduction in the monthly frequency of attacks was observed, partial responders if the reduction was between 30 and 50%, and non-responders if it was <30%. RESULTS: The treated population consisted of 37 females and 9 males with a mean age of 14.7 years. Before starting OBT-A, 58.7% of the subjects had attempted prophylactic therapy with other drugs. From OBT-A initiation to the last clinical observation, the mean duration of follow-up was 17.6 ± 13.7 SD (range: 1-48) months. The number of OBT-A injections were 3.4 ± 3 SD. Sixty eight percent of the subjects responded to treatment within the first three administrations of OBT-A. Proceeding with the number of administrations, a progressive improvement in frequency was further observed. CONCLUSIONS: The use of OBT-A in pediatric age can have benefits in terms of reduction in the frequency and intensity of headache episodes. Furthermore, treatment with OBT-A has an excellent safety profile. These data support the use of OBT-A in the treatment of childhood migraine.

Cranial autonomic symptoms and response to monoclonal antibodies targeting the Calcitonin gene-related peptide pathway: A real-world study.

Objective: Cranial autonomic symptoms (CAS), including conjunctival injection, tearing, nasal congestion or rhinorrhea, eyelid edema, miosis or ptosis, and forehead or facial sweating ipsilateral to headache, are often reported by patients with migraine during headache attacks. CAS is a consequence of the activation of the trigeminovascular system, which is the target of monoclonal antibodies acting on the CGRP pathway. Therefore, we hypothesized that patients with CAS might have higher trigeminovascular activation than those without CAS leading to a better response to anti-CGRP treatments. Methods: We performed a prospective analysis including patients with episodic or chronic migraine treated with anti-CGRP monoclonal antibodies (i.e., erenumab, fremanezumab, and galcanezumab) between 2019 and 2021. The observation period included a 12-week baseline before treatment with anti-CGRP antibodies and a 12-week treatment follow-up. We evaluated the prevalence of CAS in our cohort and compared disease characteristics and treatment response (i.e., 12-week monthly headache days and 0-29, 30-49, 50-74, 75-99, and 100% monthly headache days reduction from baseline) among patients with and without CAS using the χ2 test, Kruskal-Wallis test, and Mann-Whitney U-test. Results: Out of 136 patients, 88 (65%) had CAS. Both patients with and without CAS reported a significant decrease in monthly headache days from baseline. During the 12-week follow-up, the median difference in monthly headache days from baseline was higher in patients with CAS (-10, IQR-15 to-6) than in those without CAS (6, IQR 12 to 3; P = 0.009). However, the proportions of patients with 0 to 29, 30 to 49, 50 to 74, 75 to 99, and 100% response rates did not differ between the two groups. Conclusions: In our cohort, the presence of CAS was associated with a greater response to monoclonal antibodies targeting the CGRP pathway. CAS could be a clinical marker of trigeminovascular activation and thus be related to a better response to CGRP treatments.

Excellent Response to OnabotulinumtoxinA: Different Definitions, Different Predictors.

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.

Behavioral and psychological factors in individuals with migraine without psychiatric comorbidities.

BACKGROUND: It is well known that the course of migraine is influenced by comorbidities and that individual psychological characteristics may impact on the disease. Proper identification of psychological factors that are relevant to migraine is important to improve non-pharmacological management. This study aimed at investigating the relationship between psychological factors and migraine in subjects free of psychiatric comorbidities. METHODS: A sample of women with episodic (EM) and chronic migraine (CM) without history of psychiatric comorbidities were included in this cross-sectional study. The study also included female healthy controls (HC) without migraine or other primary headaches. We evaluated sleep, anxiety, depression, intolerance of uncertainty, decision making style and tendence to pain catastrophizing by validated self-report questionnaires or scales. Comparisons among groups were performed using ANOVA and Bonferroni post-hoc tests. Statistical significance was set at p < 0.05. RESULTS: A total of 65 women with EM (mean age ± SD, 43.9 ± 7.2), 65 women with CM (47.7 ± 8.5), and 65 HC (43.5 ± 9.0) were evaluated. In sleep domains, CM patients reported poorer overall sleep quality, more severe sleep disturbances, greater sleep medication use, higher daytime dysfunction, and more severe insomnia symptoms than HC. EM group showed better sleep quality, lower sleep disturbances and sleep medication use than CM. On the other hand, the analysis highlighted more severe daytime dysfunction and insomnia symptoms in EM patients compared to HC. In anxiety and mood domains, CM showed greater trait anxiety and a higher level of general anxiety sensitivity than HC. Specifically, CM participants were more afraid of somatic and cognitive anxiety symptoms than HC. No difference in depression severity emerged. Finally, CM reported a higher pain catastrophizing tendency, more severe feeling of helplessness, and more substantial ruminative thinking than EM and HC, whilst EM participants reported higher scores in the three above-mentioned dimensions than HC. The three groups showed similar decision-making styles, intolerance of uncertainty, and strategies for coping with uncertainty. CONCLUSIONS: Even in individuals without psychiatric comorbidities, specific behavioral and psychological factors are associated with migraine, especially in its chronic form. Proper identification of those factors is important to improve management of migraine through non-pharmacological strategies.

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.

The Enigma of New Daily Persistent Headache: What Solutions for Pediatric Age?

PURPOSE OF REVIEW: To analyze systematically the evidence currently available from the literature regarding the diagnosis, clinical characteristics, treatment and outcome of new daily persistent headache (NDPH). RECENT FINDINGS: NDPH is a primary headache characterized by an abrupt onset with continuous daily pain that can persist for many months. Although self-limiting forms have been described, NDPH is frequently associated with high disability even in children and adolescents. For this reason, it is very important to recognize it from a diagnostic point of view and to treat it. We found little specific data on NDPH in developmental age. Most of the therapy studies have been conducted on adults with conflicting data. Currently, pediatric NDPH therapy is based on experiences in adult patients and in individuals with other forms of primary chronic headache, hence the need for more pediatric studies to fill this information gap.

Different effects of air microembolism through patent foramen ovale in patients with migraine: A quantitative electroencephalogram case series.

Background: Literature suggests an association between patent foramen ovale (PFO) and migraine, mostly migraine with aura (MA). Previous data suggest that air microembolism through PFO can lead to bioelectrical abnormalities detectable at electroencephalogram (EEG) in patients with MA, thus suggesting a pathophysiological mechanism for the MA-PFO association. However, those data lack replication. Methods: Patients with MA or migraine without aura (MO) and large PFO underwent a 19-channel EEG recording before and after injection of air microbubbles. We compared EEG power before and after microbubble injection for each electrode location, for each frequency band (theta: 5-7 Hz; alpha: 8-12 Hz; beta: 13-30 Hz; lower gamma: 31-45 Hz), and for total global power (the average of EEG power at each location and frequency band). Results: We included 10 patients, four with MA and six with MO; six patients had medium-to-high migraine frequency (four or more monthly migraine days), while four had low frequency (one monthly migraine day). EEG power changes after air microembolism varied across patients. Considering the overall group, total global EEG power did not change; however, EEG power in the higher frequency ranges (beta and lower gamma) increased in patients with MA. Conclusions: We did not replicate the effects of air microembolism previously reported in patients with migraine. Aura status, migraine frequency, and medications might influence patients' response to microembolism. More refined EEG measurements are needed to clarify the dynamic role of PFO on migraine occurrence.

Migraine and Its Equivalents: What Do They Share? A Narrative Review on Common Pathophysiological Patterns.

Migraine is the first in order of frequency of the neurological disorders, affecting both adult and paediatric populations. It is also the first cause of primary headaches in children. Migraine equivalents are periodic disorders that can be associated with migraine or considered as prognostic features of a future migraine manifestation. Despite the mechanisms underlying migraine and its equivalents are not entirely clear, several elements support the hypothesis of common pathophysiological patterns shared by these conditions. The aim of this review is thus to analyze the literature in order to highlight which currently known mechanisms may be common between migraine and its equivalents.

Migraine during COVID-19: Data from Second Wave Pandemic in an Italian Cohort.

OBJECTIVES: The study aims to assess the impact of the second COVID-19 pandemic wave on migraine characteristics. METHODS: This is an observational cross-sectional study conducted on migraine patients previously interviewed during the first Italian pandemic outbreak. A second structured telephone interview was conducted between 20 November 2020 and 18 January 2021. We compared migraine characteristics among T0 (before pandemic), T1 (during the first pandemic phase), and T2 (during the second pandemic phase). RESULTS: Among the 433 patients interviewed during the first pandemic phase, 304 cases were finally considered. One hundred forty-eight patients had a control visit between March 2020 and December 2020, 120 had an in-person visit, 14 by phone, the remainder used telemedicine software provided by the hospital. Frequency of headache, number of symptomatic drugs and headache intensity worsened during T2, compared to T0 and T1, especially in episodic migraine. Headache intensity increased relating to the negative emotional impact of the pandemic. Migraine management during the pandemic did not influence the clinical outcome. CONCLUSION: The prolongation of the pandemic seems to have a negative impact on migraine evolution. The arousal and negative psychological behavior toward the COVID-19 outbreak seem to worsen migraine.

Social Distancing in Chronic Migraine during the COVID-19 Outbreak: Results from a Multicenter Observational Study.

BACKGROUND: The restrictions taken to control the rapid spread of COVID-19 resulted in a sudden, unprecedented change in people's lifestyle, leading to negative consequences on general health. This study aimed to estimate the impact of such changes on migraine severity during 2020 March-May lockdown. METHODS: Patients affected by migraine with or without aura, diagnosed by expert physicians, completed a detailed interview comprehensive of: assessment of migraine characteristics; measure of physical activity (PA) levels; measure of the intake frequency of main Italian foods; the Insomnia Severity Index (ISI) questionnaire investigating sleep disorders. RESULTS: We included 261 patients with a mean age of 44.5 ± 12.3 years. During social distancing, 72 patients (28%) reported a headache worsening, 86 (33%) an improvement, and 103 (39%) a stable headache frequency. A significant decrease of the PA levels during COVID-19 quarantine in the whole study sample was observed (median total metabolic equivalent task (METs) decreased from 1170 to 510; p < 0.001). Additionally, a significant difference was reported on median ISI scores (from 7 to 8; p < 0.001), which were increased in patients who presented a stable or worsening headache. CONCLUSIONS: Our study confirmed that the restrictions taken during the pandemic have affected the practice of PA levels and sleep quality in migraine. Hence, PA and sleep quality should be assessed to find strategies for an improvement in quality of life.

Menstrual Headache in Women with Chronic Migraine Treated with Erenumab: An Observational Case Series.

BACKGROUND: We aimed to assess the differences between menstrual and non-menstrual headache in women with chronic migraine treated with erenumab. METHODS: We included fertile women from a single center. Patients were defined as responders to erenumab if reporting a ≥50% decrease in monthly headache days, as compared to pre-treatment for more than half of the treatment period. Premenstrual days were defined as the two days preceding menstruation, while menstrual days were defined as the first three days of menstruation. RESULTS: We included 18 women (11 erenumab responders and 7 erenumab non-responders) contributing to a total of 103 menstrual cycles and 2926 days. The proportion of headache days was higher in menstrual than in premenstrual and non-menstrual days in erenumab responders (34.4% vs. 14.8% vs. 16.3%, respectively; p < 0.001) and in erenumab non-responders (71.4% vs. 53.6% vs. 48.3%, respectively; p < 0.001). Headache days with ≥2 acute medications were higher in menstrual than in premenstrual or non-menstrual headache days in erenumab non-responders (p = 0.002) but not in erenumab responders (p = 0.620). CONCLUSIONS: Our data suggest that migraine is more frequent during than outside menstrual days even in women treated with erenumab.

Early Management of OnabotulinumtoxinA Treatment in Chronic Migraine: Insights from a Real-Life European Multicenter Study.

INTRODUCTION: OnabotulinumtoxinA (BT-A) quarterly was the first treatment approved specifically for chronic migraine (CM). It is unclear whether three cycles are better than two to assess early BT-A response. METHODS: We performed a retrospective analysis on real-life prospectively collected data in 16 European headache centers. All the centers provided data on patients treated with BT-A for CM over the first three cycles of treatment. For each treatment cycle we defined patients as "good responders" if reporting a ≥ 50% reduction in monthly headache days compared with the three months before starting BT-A, "partial responders" if reporting a 30-49% reduction in monthly headache days, and "non-responders" if reporting a < 30% reduction in monthly headache days or stopping the treatment before the third cycle. RESULTS: We included 2879 patients. Seven hundred and eighty-four (64.6%) of the 1213 patients reporting a good response during the first and/or the second cycle had a good response during the third cycle; 309 (49.3%) of the 627 patients reporting a partial response (but no good response) during the first and/or the second cycle had a good response during the third cycle; only 65 (6.3%) of the 1039 patients who did not respond during both the first two cycles achieved a good response during the third cycle. Multivariate analyses showed that partial or good response during the first or the second cycle were independently associated with good response during the third cycle. CONCLUSIONS: Our data suggest that patients with CM responding to BT-A during the first two cycles will likely benefit from the third cycle of treatment, while the probability that non-responders to the first two cycles start responding during the third cycle is low. These results can help guide the individual decision to stop or continue treatment after the second cycle in patients who have not responded to the first two cycles.

Patterns of Migraine in Postmenopausal Women: A Systematic Review.

INTRODUCTION: Migraine prevalence is higher in fertile than in postmenopausal women. However, few literature data are available on the prevalence and characteristics of migraine after the menopause and on the effect of hormones in postmenopausal women with migraine. METHODS: We performed a systematic literature review of studies available on Scopus and Web of Science from the beginning off indexing until October 18th, 2020. We included both randomized trials and observational studies. RESULTS: We included 12 papers, six of which assessed the prevalence and characteristics of migraine in postmenopausal women, while the other six assessed the effect of hormones on migraine after the menopause. One of the studies was a randomized trial, while the remaining 11 were observational studies. Ten studies were clinic-based, while the remaining two were population-based. Studies assessing the prevalence and characteristics of migraine after the menopause reported inconsistent findings; in studies performed in headache clinics, likely affected by selection bias towards the most severe cases, a relevant proportion of women reported migraine worsening after the menopause. Studies assessing the effect of hormones on migraine after the menopause showed that postmenopausal hormone replacement therapy was invariably associated with migraine worsening, if containing estrogen. CONCLUSION: Our systematic review showed that migraine could be a relevant health problem in postmenopausal women, mostly in headache clinics. However, the available studies allow a limited assessment of the prevalence and characteristics of postmenopausal migraine. Further large studies are needed to better determine the burden of migraine after the menopause according to migraine characteristics and the impact of hormonal treatments.

Efficacy and safety of greater occipital nerve block for the treatment of cervicogenic headache: a systematic review.

INTRODUCTION: Cervicogenic headache (CGH) is a secondary headache disorder caused by cervical spine or neck soft tissue lesions. Despite few available evidence-based pharmacological treatments are available, greater occipital nerve blocks (GONBs) are considered as therapeutic option. AREA COVERED: In June 2020, we conducted a systematic review on Pubmed and Scopus, to summarize effectiveness and safety of GONBs in treating CGH. We included 5 observational studies and 3 nonrandomized trials reporting clinical outcomes of 140 CGH patients after GONBs. Authors performed unilateral GONBs during interictal phase (five studies) or during pain, injecting local anesthetic (four studies) or both local anesthetic and steroid (three studies) at variable timepoints. In 5 studies mean pain reduction ranged from -8.2 (at 2 weeks after the first block) to -0.1 (at 1 month after the third block); one study documented 66.6% reduction of pain intensity and another study documented a significant median reduction of pain intensity at 3 months (decreased from 5.5 to 2.3) and not at 9 months. Three studies reported minor adverse events. EXPERT OPINION: Few available studies suggest that GONBs are effective and safe in treating CGH. GONB is a high tolerable, low cost and repeatable procedure. Larger and randomized studies are needed.