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Johanna Barón-Sánchez,1 Álvaro Gutiérrez-Viedma,2 Marina Ruiz-Piñero,1 Alicia Pérez-Pérez,2 Ángel Luis Guerrero,1,3 María L Cuadrado2,4 1Headache Unit, Department of Neurology, Hospital Clínico Universitario de Valladolid, Valladolid, Spain; 2Department of Neurology, Hospital Clínico San Carlos, Madrid, Spain; 3Department of Medicine, School of Medicine, Universidad de Valladolid, Valladolid, Spain; 4Department of Medicine, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain Background: The first description of epicrania fugax (EF) reported brief painful paroxysms that start in posterior regions of the scalp and move forward to reach the ipsilateral forehead, eye, or nose. A backward variation, wherein pain stems from frontal areas and radiates to the posterior scalp, has also been acknowledged. We report four patients with features reminiscent of EF and the coexistence of forward and backward pain paroxysms.Methods: We considered all patients attending the headache outpatient office at two tertiary hospitals from March 2008 to March 2016. We enrolled four patients with paroxysms fulfilling criteria for EF and a combination of forward and backward radiations.Results: In all cases, pain paroxysms moved both in forward and backward directions with either a zigzag (n=2) or linear (n=2) trajectory. Three patients presented two stemming points, in the occipital scalp and forehead (n=2) or in the parietal area and eye (n=1), whereas the fourth patient only had a stemming point located in the parietal region. Pain quality was mainly stabbing, and its intensity was moderate (n=1) or severe (n=3). The duration of the paroxysms was highly variable (3–30 seconds), and two patients reported autonomic symptoms. Conclusion: The clinical picture presented by our patients does not fit with other types of known headache or neuralgia syndromes; we propose it corresponds to a bidirectional variant of EF. Keywords: epicrania, epicranial neuralgias, backward radiation, forward radiation

Abstract Background Recent in vivo and in vitro studies in non-neuronal and neuronal tissues have shown that different pathways of macrophage activation result in cells with different properties. Interleukin (IL)-6 triggers the classically activated inflammatory macrophages (M1 phenotype), whereas the alternatively activated macrophages (M2 phenotype) are anti-inflammatory. The objective of this study was to clarify the effects of a temporal blockade of IL-6/IL-6 receptor (IL-6R) engagement, using an anti-mouse IL-6R monoclonal antibody (MR16-1), on macrophage activation and the inflammatory response in the acute phase after spinal cord injury (SCI) in mice. Methods MR16-1 antibodies versus isotype control antibodies or saline alone were administered immediately after thoracic SCI in mice. SC tissue repair was compared between the two groups by Luxol fast blue (LFB) staining for myelination and immunoreactivity for the neuronal markers growth-associated protein (GAP)-43 and neurofilament heavy 200 kDa (NF-H) and for locomotor function. The expression of T helper (Th)1 cytokines (interferon (IFN)-γ and tumor necrosis factor-α) and Th2 cytokines (IL-4, IL-13) was determined by immunoblot analysis. The presence of M1 (inducible nitric oxide synthase (iNOS)-positive, CD16/32-positive) and M2 (arginase 1-positive, CD206-positive) macrophages was determined by immunohistology. Using flow cytometry, we also quantified IFN-γ and IL-4 levels in neutrophils, microglia, and macrophages, and Mac-2 (macrophage antigen-2) and Mac-3 in M2 macrophages and microglia. Results LFB-positive spared myelin was increased in the MR16-1-treated group compared with the controls, and this increase correlated with enhanced positivity for GAP-43 or NF-H, and improved locomotor Basso Mouse Scale scores. Immunoblot analysis of the MR16-1-treated samples identified downregulation of Th1 and upregulation of Th2 cytokines. Whereas iNOS-positive, CD16/32-positive M1 macrophages were the predominant phenotype in the injured SC of non-treated control mice, MR16-1 treatment promoted arginase 1-positive, CD206-positive M2 macrophages, with preferential localization of these cells at the injury site. MR16-1 treatment suppressed the number of IFN-γ-positive neutrophils, and increased the number of microglia present and their positivity for IL-4. Among the arginase 1-positive M2 macrophages, MR16-1 treatment increased positivity for Mac-2 and Mac-3, suggestive of increased phagocytic behavior. Conclusion The results suggest that temporal blockade of IL-6 signaling after SCI abrogates damaging inflammatory activity and promotes functional recovery by promoting the formation of alternatively activated M2 macrophages.

Backgrounds: We aim to evaluate changes in pressure pain sensitivity before and after cardiac surgery using topographical sensitivity maps utilizing a pressure algometer., Methods: Pressure pain thresholds over 17 thoracic points and 4 distant pain-free points were assessed in 70 patients (women: 29, age: 67.5 years), before and at 1, 3, and 7 postoperative days. Thoracic topographical pressure pain sensitivity maps were calculated at all follow-ups. Postoperative pain was recorded at each follow-up on a numerical pain rate scale., Results: Postoperative pain intensity decreased from 6.4 (SD 1.0) on the first postoperative day to 5.5 (SD 1.9) on the third and to 4.5 (SD 1.7) on the seventh day ( p < 0.001). The mixed-model ANOVA revealed that the lowest pressure pain thresholds were observed one day after surgery, increased slightly during follow-up, and were lower at the xiphoid process. Significant negative correlations between postoperative pain intensity and pressure pain thresholds were observed at each time point in thoracic measures (all, p < 0.01), but not with pressure pain thresholds from distant pain-free areas., Conclusions: Postoperative pain after cardiac surgery can be objectively quantified using algometry. Pressure pain hyperalgesia was associated with the intensity of postoperative pain.

Background: Despite the number of research studies regarding the individual burden of migraine, few studies have examined its impact on the patients' partners. We aim to assess migraine effects on the patients' partners on sentimental relationship, children relationship, friendship, and work, as well as the caregiver burden, anxiety and/or depression., Methods: A cross-sectional observational study was conducted through an online survey of partners of patients with migraine followed-up in 5 Headache Units. Questions about the 4 areas of interest and 2 scales (Hospital Anxiety and Depression Scale and Zarit scale) were included. Scores were compared against the population prevalence., Results: One hundred and fifty-five answers were analysed. Among the patient's partners 135/155 (87.1%) were men, with a mean age of 45.6 ± 10.1 years. Migraine's main effects on partners were observed in the sentimental relationship and items concerning children and friendships, with a minor impact at work. Partners showed a moderate burden (12/155 = 7.7% [4.1%-13.1%]), and a higher moderate-severe anxiety rate (23/155 = 14.8% [9.6%-21.4%]), and similar depression rate (5/155 = 3.2% [1.1%-7.3%]) compared to the National Health Survey., Conclusions: The burden of migraine impacts the partners' personal relationship, childcare, friendship and work. Moreover, certain migraine partners showed a moderate burden according to Zarit scale and higher anxiety levels than the Spanish population., (Copyright © 2023 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)

Diffusion Tensor Imaging (DTI) is the most employed method to assess white matter properties using quantitative parameters derived from diffusion MRI, but it presents known limitations that restrict the evaluation of complex structures. The objective of this study was to validate the reliability and robustness of complementary diffusion measures extracted with a novel approach, Apparent Measures Using Reduced Acquisitions (AMURA), with a typical diffusion MRI acquisition from a clinical context in comparison with DTI with application to clinical studies. Fifty healthy controls, 51 episodic migraine and 56 chronic migraine patients underwent single-shell diffusion MRI. Four DTI-based and eight AMURA-based parameters were compared between groups with tract-based spatial statistics to establish reference results. On the other hand, following a region-based analysis, the measures were assessed for multiple subsamples with diverse reduced sample sizes and their stability was evaluated with the coefficient of quartile variation. To assess the discrimination power of the diffusion measures, we repeated the statistical comparisons with a region-based analysis employing reduced sample sizes with diverse subsets, decreasing 10 subjects per group for consecutive reductions, and using 5,001 different random subsamples. For each sample size, the stability of the diffusion descriptors was evaluated with the coefficient of quartile variation. AMURA measures showed a greater number of statistically significant differences in the reference comparisons between episodic migraine patients and controls compared to DTI. In contrast, a higher number of differences was found with DTI parameters compared to AMURA in the comparisons between both migraine groups. Regarding the assessments reducing the sample size, the AMURA parameters showed a more stable behavior than DTI, showing a lower decrease for each reduced sample size or a higher number of regions with significant differences. However, most AMURA parameters showed lower stability in relation to higher coefficient of quartile variation values than the DTI descriptors, although two AMURA measures showed similar values to DTI. For the synthetic signals, there were AMURA measures with similar quantification to DTI, while other showed similar behavior. These findings suggest that AMURA presents favorable characteristics to identify differences of specific microstructural properties between clinical groups in regions with complex fiber architecture and lower dependency on the sample size or assessing technique than DTI., 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 © 2023 Martín-Martín, Planchuelo-Gómez, Guerrero, García-Azorín, Tristán-Vega, de Luis-García and Aja-Fernández.)

Introduction: Headache is a frequent cause of consultation; it is important to detect patients with secondary headache, particularly high-risk secondary headache. Such systems as the Manchester Triage System (MTS) are used for this purpose. This study aims to evaluate the frequency of undertriage in patients attending the emergency department due to headache., Material and Methods: We studied a series of consecutive patients who came to the emergency department with headache and presenting some warning sign, defined as the presence of signs leading the physician to request an emergency neuroimaging study and/or assessment by the on-call neurologist. The reference diagnosis was established by neurologists. We evaluated the MTS triage level assigned and the presence of warning signs that may imply a higher level than that assigned., Results: We registered a total of 1120 emergency department visits due to headache, and 248 patients (22.8%) were eligible for study inclusion. Secondary headache was diagnosed in 126 cases (50.8% of the sample; 11.2% of the total), with 60 cases presenting high-risk secondary headache (24.2%; 5.4%). According to the MTS, 2 patients were classified as immediate (0.8%), 26 as very urgent (10.5%), 147 as urgent (59.3%), 68 as normal (27.4%), and 5 as not urgent (2%). The percentage of patients undertriaged was 85.1% in the very urgent classification level and 23.3% in the urgent level., Conclusion: During the study period, at least one in 10 patients attending the emergency department due to headache had secondary headache; one in 20 had high-risk secondary headache. The MTS undertriaged most patients with warning signs suggesting a potential emergency., (Copyright © 2020 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)

Headache is among the most frequently reported symptoms after resolution of COVID-19. We assessed structural brain changes using T1- and diffusion-weighted MRI processed data from 167 subjects: 40 patients who recovered from COVID-19 but suffered from persistent headache without prior history of headache (COV), 41 healthy controls, 43 patients with episodic migraine and 43 patients with chronic migraine. To evaluate gray matter and white matter changes, morphometry parameters and diffusion tensor imaging-based measures were employed, respectively. COV patients showed significant lower cortical gray matter volume and cortical thickness than healthy subjects (p < 0.05, false discovery rate corrected) in the inferior frontal and the fusiform cortex. Lower fractional anisotropy and higher radial diffusivity (p < 0.05, family-wise error corrected) were observed in COV patients compared to controls, mainly in the corpus callosum and left hemisphere. COV patients showed higher cortical volume and thickness than migraine patients in the cingulate and frontal gyri, paracentral lobule and superior temporal sulcus, lower volume in subcortical regions and lower curvature in the precuneus and cuneus. Lower diffusion metric values in COV patients compared to migraine were identified prominently in the right hemisphere. COV patients present diverse changes in the white matter and gray matter structure. White matter changes seem to be associated with impairment of fiber bundles. Besides, the gray matter changes and other white matter modifications such as axonal integrity loss seemed subtle and less pronounced than those detected in migraine, showing that persistent headache after COVID-19 resolution could be an intermediate state between normality and migraine., (© 2022. The Author(s).)

Onabotulinumtoxin A (onabotA) has shown efficacy in chronic migraine (CM), with good tolerability and a low rate of adverse effects, most of them not severe. The aim of this study is to evaluate tolerability and adverse effects of onabotA in clinical practice and to analyze if there is a relationship between tolerability to treatment administration, adverse effects' (AEs) occurrence and clinical response. We included patients with CM that received treatment with onabotA for the first time. Tolerability to treatment was evaluated by a 0-10 numeric rating scale (0: worst possible, 10: optimal tolerability). We assessed the presence of AEs by using a standardized questionnaire. Treatment response was based on the 50 and 75% responder rate between weeks 20 and 24, compared with the baseline, according to headache diaries. We analyzed whether the tolerability was associated with a higher frequency of AEs or a higher probability of clinical response. We included 105 patients, 87.7% female, with an age of 43.9 ± 10.7 years. Mean tolerability was 7.8/10 and 7.2/10 in the first and second onabotA administration, respectively. AEs were reported by (first-second) 71.4-68.6% patients. The percentage of patients with a 50% response was 56.3%. There was no association between tolerability and AEs' occurrence or clinical response.

Aim: To evaluate the diagnostic accuracy of the SNNOOP10 list in the detection of high-risk headaches., Methods: Patients that visited the Hospital Clínico San Carlos (Madrid) emergency department due to headache that were allocated to a Manchester Triage System level between critical and urgent were prospectively included but retrospectively analysed. A researcher blind to the patients' diagnosis administered a standardised questionnaire and afterwards a neurologist blind to the questionnaire results diagnosed the patient according to the International Classification of Headache Disorders. The primary endpoint was to assess the sensitivity of the SNNOOP10 list in the detection of high-risk headaches. Secondary endpoints included the evaluation of the sensitivity, specificity, positive predictive value, negative predictive value and area under the curve of each SNNOOP10 item., Results: Between April 2015 and October 2021, 100 patients were included. Patients were 44 years old (inter-quartile range: 33.6-64.7) and 57% were female. We identified 37 different diagnoses. Final diagnosis was a primary headache in 33%, secondary headache in 65% and cranial neuralgia in 2%. There were 46 patients that were considered as having high-risk headache. Patients from the primary headache group were younger and more frequently female. Sensitivity of SNNOOP10 list was 100% (95% confidence interval: 90.2%-100%). The items with higher sensitivity were neurologic deficit or disfunction (75.5%), pattern change or recent onset of the headache (64.4%), onset after 50 years (64.4%). The most specific items were posttraumatic onset of headache (94.5%), neoplasm in history (89.1%) and systemic symptoms (89%). The area under the curve of the SNNOOP10 list was 0.66 (95% CI: 0.55-0.76)., Conclusion: The red flags from the SNNOOP10 list showed a 100% sensitivity in the detection of high-risk headache disorders.

Background: Sensitization mechanisms are thought to play a role in the perception of pain in people with cluster headache. No study has investigated the relation between the spatial extent of pain in cluster headache and measures of sensitization or other clinical features., Objective: Our aim was to investigate if the size of the painful area in people with cluster headache relates to widespread pressure sensitivity, headache features, and psychological outcomes., Methods: Forty men with episodic cluster headache reported their symptoms on a digital body chart and pain extent was calculated. Pressure pain thresholds were assessed locally over the temporalis muscle and the C5-C6 joint and at a remote site over the tibialis anterior to assess widespread pressure sensitivity. Clinical features of headache attacks, and anxiety/depressive levels were also assessed. Patients were assessed during a period of remission 6 months after their last pain attack and after treatment discontinuation., Results: Thirty-two (80%) and thirty (75%) patients reported their headaches in the orbital and the frontal areas, respectively. No significant associations (rho values ranging from -0.228 to 0.187, P values ranging from 0.157 to 0.861) were found between pain extent and pressure pain thresholds in trigeminal, extra-trigeminal, and distant pain-free areas, headache clinical features, and anxiety and depressive levels., Conclusion: Pain extent in the trigemino-cervical area was not related to the degree of pressure pain sensitivity or headache features in men with episodic cluster headache during a period of remission.

Background (1): Headache is a prevalent symptom experienced during ongoing SARS-CoV-2 infection, but also weeks after recovery. Whether cardio-pulmonary dysfunction contributes causally to headache persistence is unknown. Methods (2): We conducted a case-control analysis nested in a prospective cohort study. Individuals were recruited from August 2020 to December 2020. Patients were grouped according to the presence or absence of long-COVID headache for three months after COVID-19 resolution. We compared demographic data, clinical variables, cardio-pulmonary laboratory biomarkers, quality of life, and cardio-pulmonary function between groups. Results (3): A cohort of 70 COVID-19 patients was evaluated. Patients with headaches (n = 10; 14.3%) were more frequently female (100% vs. 58.4%; p = 0.011) and younger (46.9 ± 8.45 vs. 56.13 ± 12 years; p = 0.023). No between-group differences in laboratory analysis, resting echocardiography, cardio-pulmonary exercise test, or pulmonary function tests were observed. Conclusion (4): In this exploratory study, no significant differences in cardio-pulmonary dysfunction were observed between patients with and without long-COVID headache during mid-term follow-up.

Introduction: To determine whether preoperative symptomatic neurological complication (SNC) predicts a worse prognosis of patients with active left-sided infective endocarditis who required early surgery. Methods: We conducted a retrospective chart review and analyzed risk factors for SNCs and immediate, medium-term, and long-term mortality in patients with active left-sided infective endocarditis who required early surgery (median follow-up: 70.5 months). Results: Of 212 included patients, preoperative SNCs occurred in 22.1%. Independent risk factors for preoperative SNC included early hospital admission (<10 days after symptoms onset), duration of antibiotic therapy <7 days, vegetation diameter > 30 mm, preoperative chronic therapy with steroids, and peripheral embolism. A new postoperative SNC occurred in 12.7% of patients. No significant differences related to preoperative or postoperative SNCs were observed in postoperative mortality (29.8% vs. 31.5%) or during follow-up. No significant differences in postoperative mortality were observed between hemorrhagic or ischemic SNCs. There was a non-significant trend to increased mortality in patients who underwent surgery within 7 days of presenting with SNC (55.5%) compared to those who underwent surgery more than 7 days after SNC (33.3%) ( P = 0.171). Concomitant risk of mortality or postoperative hemorrhagic transformation increased when surgery is required during the first week after preoperative SNC (77.5% vs. 25%) ( P = 0.017). Conclusions: Patients with active left-sided infective endocarditis who need early hospital admission are at a higher risk of SNC. Mortality is higher in patients who underwent surgery within 7 days of SNC, but mortality of early surgery is acceptable after the first week of preoperative ischemic or hemorrhagic complication. We have not been able to demonstrate that preoperative nor postoperative SNCs predicted a reduced immediate, medium-term, or long-term survival in the population analyzed in this study., 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 © 2021 Carrascal, Segura, Velasco and Guerrero.)

Background: Face-to-face procedures have been postponed during COVID-19 pandemic. We aim to evaluate the impact of onabotulinumtoxinA follow-up delay in migraine during COVID-19 pandemic., Methods: Subjective worsening, intensity of migraine attacks, and frequency of headache and migraine were retrospectively compared between patients with unmodified and interrupted onabotulinumtoxinA follow-up in Headache Units., Results: We included 67 patients with chronic migraine or high-frequency episodic migraine under onabotulinumtoxinA treatment, 65 (97.0%) female, 44.5 ± 12.1 years old. Treatment administration was voluntarily delayed in 14 (20.9%) patients and nine (13.4%) were unable to continue follow-up. Patients with uninterrupted follow-up during lockdown presented 7.6 and 8.1 less monthly days with headache (adjusted p = 0.017) and migraine attacks (adjusted p = 0.009) compared to patients whose follow-up was interrupted, respectively., Conclusion: Involuntary delay of onabotulinumtoxinA follow-up in patients with migraine due to COVID-19 pandemic was associated with a higher frequency of headache and migraine attacks. Safe administration of onabotulinumtoxinA during lockdown should be promoted., (© 2021. Fondazione Società Italiana di Neurologia.)

Objective: Previous studies have demonstrated that emotional stress, changes in lifestyle habits and infections can worsen the clinical course of migraine. We hypothesize that changes in habits and medical care during coronavirus disease 2019 (COVID-19) lockdown might have worsened the clinical course of migraine., Design: Retrospective survey study collecting online responses from migraine patients followed-up by neurologists at three tertiary hospitals between June and July 2020., Methods: We used a web-based survey that included demographic data, clinical variables related with any headache (frequency) and migraine (subjective worsening, frequency, and intensity), lockdown, and symptoms of post-traumatic stress., Results: The response rate of the survey was 239/324 (73.8%). The final analysis included 222 subjects. Among them, 201/222 (90.5%) were women, aged 42.5 ± 12.0 (mean±SD). Subjective improvement of migraine during lockdown was reported in 31/222 participants (14.0%), while worsening in 105/222 (47.3%) and was associated with changes in migraine triggers such as stress related to going outdoors and intake of specific foods or drinks. Intensity of attacks increased in 67/222 patients (30.2%), and it was associated with the subjective worsening, female sex, recent insomnia, and use of acute medication during a headache. An increase in monthly days with any headache was observed in 105/222 patients (47.3%) and was related to symptoms of post-traumatic stress, older age and living with five or more people., Conclusions: Approximately half the migraine patients reported worsening of their usual pain during the lockdown. Worse clinical course in migraine patients was related to changes in triggers and the emotional impact of the lockdown., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Academy of Pain Medicine.All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

OnabotulinumtoxinA is one of the main preventive treatments for chronic migraine. Despite that up to one third of patients with chronic migraine suffer from daily headache, these individuals have hardly been studied. We conducted a prospective cohort study, including patients with chronic migraine and treated with OnabotulinumtoxinA according to the PREEMPT paradigm. The primary endpoint was to assess whether patients with chronic migraine and daily headache had a different response after three sessions of OnabotulinutoxinA than patients without daily headache. The secondary endpoint was to analyse the presence of predictive factors that could be associated with a higher response to OnabotulinumtoxinA. Patients with daily headache had a reduction of 14.9 (SD: 9.7) headache days per month, patients with 22-29 headache days a reduction of 10.6 (SD: 9.9) days, and patients with 15-21 headache days a reduction of 8.6 (SD: 7.1) days ( p < 0.001). In the univariate regression analysis, a higher number of headache days per month at baseline was associated with higher odds of reduction in the number of headache days per month after OnabotulinumtoxinaA treatment (OR: 0.474, 95% CI: 0.278-0.670, p < 0.001). This association was maintained in the multivariate regression analysis (OR: 0.540, 95% CI: 0.333-0.746, p < 0.001). In our sample, daily headache was not associated with a worse response to OnabotulinumtoxinA treatment. A higher frequency of headache at baseline was a predictor of better response to OnabotulinumtoxinA treatment.

Objective: Linear headache has been recently described as an episodic or chronic unilateral pain distributed along a fixed linear trajectory, which combines some characteristics of epicrania fugax and nummular headache. The aim of this study was to describe the clinical characteristics and therapeutic response of a series of 16 new patients., Design: This is an observational study with a series of cases., Setting: The study period encompassed June 2014 to June 2019. Demographic, clinical, and therapeutic response data were recorded., Methods: We included all consecutive patients who presented pain with the following characteristics: sharply contoured, fixed in size and shape, with linear shape, without movement along a trajectory, and not circumscribed to the territory of any nerve., Results: Twelve patients were women, and four were men. The mean age at onset was 40.1 years. Pain was described as pressing in seven patients, burning in five, and electric or stabbing in two each. Symptomatic treatment had been used by 13 patients (81.2%), with analgesics being the most frequent treatment used. Thirteen patients received preventive treatment. The response to oral medications and anesthetic blockade was insufficient. OnabotulinumtoxinA was used in six cases, with an optimal (>75%) response observed in half., Conclusion: Linear headache appears to be a distinct headache syndrome from epicrania fugax or nummular headache. Preventive treatment is often required. The drug with the best response was onabotulinumtoxinA., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Academy of Pain Medicine.All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Headache is a leading reason for presentation to the emergency department (ED) with migraine being the most frequently headache. To ensure the adequate staffing of healthcare providers during peak times of headache visits, we analyzed the temporal distribution of emergency department visits in patients presenting with headache and/or migraine. Research design and methods: The authors conducted an ecological study, including all consecutive visits to the ED for headache. Patients were classified according to the IHS Classification. We analyzed circadian, circaseptan and circannual patterns for number of visits, comparing migraine patients with other headache patients. Results: There were 2132 ED visits for headache, including primary headache in 1367 (64.1%) cases; migraine in 963 (45.2%); secondary headache in 404 (18.9%); and unspecified headache in 366 (17.1%). The circadian pattern showed peaks around 11:00-13:00 and 17:00-19:00, with visits during the night shift 45% less frequent (p < 0.001). The circaseptan pattern showed a peak on Monday-Tuesday and a low point on Sunday (p < 0.007). The circannual pattern peaked in March and decreased in June. Conclusions: ED visits for headache showed specific circadian, circaseptan and circannual variations. No differences were found in these patterns when comparing migraine patients to other headache patients.

Introduction: The evaluation of red flags is crucial for the accurate the diagnosis of headache disorders, especially for thunderclap headache. We analysed if secondary headache disorders were adequately ruled out in patients that presented to the emergency room with thunderclap headache., Methods: In this retrospective cohort study, we screened all patients that visited the emergency room for headache, including those that described thunderclap headache. We measured the frequency with which secondary causes were not adequately ruled out. We analysed the order of the exams, the final diagnosis, and the time elapsed between arrival, initial request for imaging, and the completion of the imaging., Results: We screened 2132 patients, and 42 (1.9%) fulfilled eligibility criteria. Mean age was 43.1 ± 17.1 years, and 57% of patients were female. For 22 (52.4%) patients, the work-up was incomplete. Vascular study was missing in 16 (38.1%) patients, cerebrospinal fluid evaluation in nine (21.4%), and magnetic resonance imaging in seven (16.7%), with multiple assessments missing in six (14.3%). There were ten different combinations in which the exams were performed, with the most frequent being the second exam's cerebral spinal fluid evaluation in 18 (52.9%) and the computed tomography angiogram in 10 (29.4%). A secondary cause of thunderclap headache was found in 16 (38.1%) patients, and four (9.5%) had a primary headache diagnosis after an adequate and complete study., Conclusions: Thunderclap onset was described in one of every 50 patients that visited the emergency room for headache. More than half of these patients were not adequately managed. More than a third of thunderclap headache patients had a secondary cause.

To date, two randomized, controlled studies support the use of candesartan for migraine prophylaxis but with limited external validity. We aim to evaluate the effectiveness and tolerability of candesartan in clinical practice and to explore predictors of patient response. Retrospective cohort study including all patients with migraine who received candesartan between April 2008-February 2019. The primary endpoint was the number of monthly headache days during weeks 8-12 of treatment compared to baseline. Additionally, we evaluated the frequency during weeks 20-24. We analysed the percentage of patients with 50% and 75% response rates and the retention rates after three and 6 months of treatment. 120/4121 patients were eligible, aged 45.9 [11.5]; 100 (83.3%) female. Eighty-four patients (70%) had chronic migraine and 53 (42.7%) had medication-overuse headache. The median number of prior prophylactics was 3 (Inter-quartile range 2-5). At baseline, patients had 20.5 ± 8.5 headache days per month, decreasing 4.3 ± 8.4 days by 3 months (weeks 12-16) and by 4.7 ± 8.7 days by 6 months (paired Student's t-test, p < 0.001). The percentage of patients with a 50% response was 32.5% at 3 months and 31.7% at 6 months, while the retention rate was 85.0% and 58.3%. The number of prior treatments (Odds ratio 0.79, 95% CI 0.64-0.97) and the presence of daily headache (Odds ratio 0.39, 95% CI 0.16-0.97) were associated with a lower probability of response. Candesartan showed beneficial effects in the preventive treatment of migraine in clinical practice, including patients with chronic migraine, medication-overuse headache and resistance to prior prophylactics.

Background : Triptanophobia is the excessive and inadequately justified concern about potential risks of triptans. We evaluated causes and consequences of nonuse of triptans in chronic migraine (CM) Methods : Case-control study. We included CM patients firstly referred to aheadache unit. Patients were cases or controls depending on whether they were triptan naïve, or not. We analyzed if nonuse of triptans was justified by formal contraindications or adverse events. We assessed if triptan naïve patients had higher frequency of vascular risk factors (VRF), contraceptive drugs or older age. Results : We included 941 patients, 247 (26.2%) triptan users. Triptans had been discontinued due to tolerability in 116 patients (12.3%), being 578 patients (61.4%) triptan naïve. Formal contraindications were found in 23 patients (2.4%). Frequency of VRF, contraceptive drugs or age did not differ between the groups (p > 0.1). Triptan users consumed symptomatic medications fewer days/month (13.9 vs 17.1, p < 0.001), were under prophylactic treatment more frequently (79.4% vs 34.8%, p < 0.001) and had medication overuse headache less frequently (55.1% vs. 63.0%, p = 0.03). Conclusion : Triptans were not used by three-quartersof CM patients. Nonuse of triptans was not justified by tolerability, frequency of contraindications, or frequency of VRF. Expert opinion : In the present study, we evaluated causes and consequences of the nonuse of triptans in CM sufferers. We analyzed frequency of triptan use in CM patients. We compared, between triptan users and triptan naïve patients, the presence of contraindications, frequency of vascular risk factors, and differences in management prior to the referral to a headache unit.

Objective: The analysis of particular (electroencephalographic) EEG frequency bands has revealed new insights relative to the neural dynamics that, when studying the EEG spectrum as a whole, would have remained hidden. This study is aimed at characterizing spectral resting state EEG patterns for assessing possible differences of episodic and chronic migraine during the interictal period. For that purpose, a novel methodology for analyzing specific frequencies of interest was performed., Methods: Eighty-seven patients with migraine (45 with episodic and 42 with chronic migraine) and 39 age- and sex-matched controls performed a resting-state EEG recording. Spectral measures were computed using conventional frequency bands. Additionally, particular frequency bands were determined to distinguish between controls and migraine patients, as well as between migraine subgroups., Results: Frequencies ranging from 11.6 Hz to 12.8 Hz characterized migraine as a whole, with differences evident in the central and left parietal regions (controlling for false discovery rate). An additional band between 24.1 Hz and 29.8 Hz was used to discriminate between migraine subgroups. Interestingly, the power in this band was positively correlated with time from onset in episodic migraine, but no correlation was found for chronic migraine., Conclusions: Specific frequency bands were proposed to identify the spectral characteristics of the electrical brain activity in migraine during the interictal stage. Our findings support the importance of discriminating between migraine subgroups to avoid hiding relevant features in migraine., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Headache is a common symptom in systemic infections, and one of the symptoms of the novel coronavirus disease 2019 (COVID-19). The objective of this study was to characterize the phenotype of COVID-19 headache via machine learning. Methods: We performed a cross-sectional study nested in a retrospective cohort. Hospitalized patients with COVID-19 confirmed diagnosis who described headache were included in the study. Generalized Linear Models and Principal Component Analysis were employed to detect associations between intensity and self-reported disability caused by headache, quality and topography of headache, migraine features, COVID-19 symptoms, and results from laboratory tests. Results: One hundred and six patients were included in the study, with a mean age of 56.6 ± 11.2, including 68 (64.2%) females. Higher intensity and/or disability caused by headache were associated with female sex, fever, abnormal platelet count and leukocytosis, as well as migraine symptoms such as aggravation by physical activity, pulsating pain, and simultaneous photophobia and phonophobia. Pain in the frontal area (83.0% of the sample), pulsating quality, higher intensity of pain, and presence of nausea were related to lymphopenia. Pressing pain and lack of aggravation by routine physical activity were linked to low C-reactive protein and procalcitonin levels. Conclusion: Intensity and disability caused by headache attributed to COVID-19 are associated with the disease state and symptoms. Two distinct headache phenotypes were observed in relation with COVID-19 status. One phenotype seems to associate migraine symptoms with hematologic and inflammatory biomarkers of severe COVID-19; while another phenotype would link tension-type headache symptoms to milder COVID-19., 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 © 2020 Planchuelo-Gómez, Trigo, de Luis-García, Guerrero, Porta-Etessam and García-Azorín.)

Introduction: Headache is a common symptom of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this study, we aimed to characterize the phenotype of headache attributed to SARS-CoV-2 infection and to test the International Classification of Headache Disorders (ICHD-3) phenotypic criteria for migraine and tension-type headache., Methods: The study design was a cross-sectional study nested in a cohort. We screened all consecutive patients that were hospitalized and had a positive SARS-CoV-2 test. We included patients that described headache if the headache was not better explained by another ICHD-3 diagnosis. Patients were interviewed by two neurologists., Results: We screened 580 patients and included 130 (mean age 56 years, 64% female). Headache was the first symptom of the infection in 26% of patients and appeared within 24 hours in 62% of patients. The headache was bilateral in 85%, frontal in 83%, and with pressing quality in 75% of patients. Mean intensity was 7.1, being severe in 64%. Hypersensitivity to stimuli occurred in 57% of patients. ICHD-3 criteria for headache attributed to systemic viral infection were fulfilled by 94% of patients; phenotypic criteria for migraine were fulfilled by 25% of patients, and tension-type headache criteria by 54% of patients., Conclusion: Headache attributed to SARS-CoV-2 infection in hospitalized patients has severe intensity, frontal predominance and oppressive quality. It occurs early in the course of the disease. Most patients fulfilled ICHD-3 criteria for headache attributed to systemic viral infection; however, the phenotype might resemble migraine in a quarter of cases and tension-type headache in half of the patients.

Objective: This study evaluates different parameters describing the gray matter structure to analyze differences between healthy controls, patients with episodic migraine, and patients with chronic migraine., Design: Cohort study., Setting: Spanish community., Subjects: Fifty-two healthy controls, 57 episodic migraine patients, and 57 chronic migraine patients were included in the study and underwent T1-weighted magnetic resonance imaging acquisition., Methods: Eighty-four cortical and subcortical gray matter regions were extracted, and gray matter volume, cortical curvature, thickness, and surface area values were computed (where applicable). Correlation analysis between clinical features and structural parameters was performed., Results: Statistically significant differences were found between all three groups, generally consisting of increases in cortical curvature and decreases in gray matter volume, cortical thickness, and surface area in migraineurs with respect to healthy controls. Furthermore, differences were also found between chronic and episodic migraine. Significant correlations were found between duration of migraine history and several structural parameters., Conclusions: Migraine is associated with structural alterations in widespread gray matter regions of the brain. Moreover, the results suggest that the pattern of differences between healthy controls and episodic migraine patients is qualitatively different from that occurring between episodic and chronic migraine patients., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Headache is a frequent cause of consultation; it is important to detect patients with secondary headache, particularly high-risk secondary headache. Such systems as the Manchester Triage System (MTS) are used for this purpose. This study aims to evaluate the frequency of sub-triage in patients attending the Emergency Department due to headache., Material and Methods: We studied a series of consecutive patients who came to the Emergency Department with headache and presenting some warning sign, defined as the presence of signs leading the physician to request an emergency neuroimaging study and/or assessment by the on-call neurologist. The reference diagnosis was established by neurologists. We evaluated the MTS triage level assigned and the presence of warning signs that may imply a higher level than that assigned., Results: We registered a total of 1,120 emergency department visits due to headache, and 248 patients (22.8%) were eligible for study inclusion. Secondary headache was diagnosed in 126 cases (50.8% of the sample; 11.2% of the total), with 60 cases presenting high-risk secondary headache (24.2%; 5.4%). According to the MTS, two patients were classified as immediate (0.8%), 26 as very urgent (10.5%), 147 as urgent (59.3%), 68 as normal (27.4%), and five as not urgent (2%). The percentage of patients under-triaged was 85.1% in the very urgent classification level and 23.3% in the urgent level., Conclusion: During the study period, at least one in 10 patients attending the Emergency Department due to headache had secondary headache; one in 20 had high-risk secondary headache. The MTS under-triaged most patients with warning signs suggesting a potential emergency., (Copyright © 2020 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.)

The white matter state in migraine has been investigated using diffusion tensor imaging (DTI) measures, but results using this technique are conflicting. To overcome DTI measures, we employed ensemble average diffusion propagator measures obtained with apparent measures using reduced acquisitions (AMURA). The AMURA measures were return-to-axis (RTAP), return-to-origin (RTOP) and return-to-plane probabilities (RTPP). Tract-based spatial statistics was used to compare fractional anisotropy, mean diffusivity, axial diffusivity and radial diffusivity from DTI, and RTAP, RTOP and RTPP, between healthy controls, episodic migraine and chronic migraine patients. Fifty healthy controls, 54 patients with episodic migraine and 56 with chronic migraine were assessed. Significant differences were found between both types of migraine, with lower axial diffusivity values in 38 white matter regions and higher RTOP values in the middle cerebellar peduncle in patients with a chronic migraine ( p < 0.05 family-wise error corrected). Significantly lower RTPP values were found in episodic migraine patients compared to healthy controls in 24 white matter regions ( p < 0.05 family-wise error corrected), finding no significant differences using DTI measures. The white matter microstructure is altered in a migraine, and in chronic compared to episodic migraine. AMURA can provide additional results with respect to DTI to uncover white matter alterations in migraine., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript or in the decision to publish the results.

Objective: In this study, we aimed to evaluate the frequency of the main red flags in patients with headache who do have Covid-19., Background: Headache is one of the most frequent neurologic symptoms of Coronavirus disease 2019 (Covid-19). Diagnosis of secondary headache disorders is still based on the presence of red flags., Design and Methods: Cross-sectional study of hospitalized patients with confirmed Covid-19 disease. We interrogated every patient about the presence of headache and if so, a headache expert conducted a structured interview assessing the presence and type of the main red flags. We evaluated the presence of laboratory abnormalities on admission., Results: We screened 576 consecutive patients, 130/576 (22.6%) described headache, and 104 were included in the study. Mean age of patients was 56.7 (standard deviation: 11.2) and 66/104 (63.4%) were female. Red flags concerning prior medical history were present in 79/104 (76.0%) cases, and those related to the headache itself were observed in 99/104 (95.2%) patients. All patients 104/104 (100%) described systemic symptoms and 86/104 (82.7%) some neurologic symptoms. Laboratory results were abnormal in 98/104 (94.2%) cases. The most frequent red flags were fever, in 93/104 (89.4%) patients, cough, in 89/104 (85.6% cases), and increased C-reactive protein in 84/100 (84.0%) cases., Conclusion: In patients with Covid-19 that described the headache red flags were present in most cases. There was not any universal red flag, being necessary the comprehensive evaluation of all of them., (© 2020 American Headache Society.)

Background: Epicrania fugax consists of brief paroxysms of pain, which radiate in a line or in zigzag trajectory across the surface of the scalp or the face., Methods: A prospective, descriptive study was performed in five patients presenting with an epicrania fugax-type pain with extracephalic irradiation., Results: All patients were women, and the mean age at onset was 59.8 (standard deviation, 10.9). They had unilateral paroxysms of electrical pain starting at a particular point in the head (parietal, n = 3; vertex, n = 1; frontal, n = 1) and rapidly radiating downwards in a lineal trajectory to reach extracephalic regions (ipsilateral limbs, n = 2; shoulder, n = 2; low neck, n = 1) in 1-3 seconds. Pain intensity was moderate or severe. Three patients had nummular headache at the point where the paroxysms originated. One patient had spontaneous remission, and four patients achieved complete or almost complete response with therapy (onabotulinumtoxinA, n = 2; indomethacin, n = 1; amitriptyline, n = 1; lamotrigine, n = 1)., Conclusion: The spectrum of epicrania fugax may include paroxysms with extracephalic irradiation. The propagation of pain beyond the head and the face supports the involvement of central mechanisms in the pathophysiology of this entity.

Introduction: Headache is one of the most frequent neurologic manifestations in COVID-19. We aimed to analyze which symptoms and laboratory abnormalities were associated with the presence of headache and to evaluate if patients with headache had a higher adjusted in-hospital risk of mortality., Methods: Retrospective cohort study. We included all consecutive patients admitted to the Hospital with confirmed SARS-CoV-2 infection between March 8th and April 11th, 2020. We collected demographic data, clinical variables and laboratory abnormalities. We used multivariate regression analysis., Results: During the study period, 576 patients were included, aged 67.2 (SD: 14.7), and 250/576 (43.3%) being female. Presence of headache was described by 137 (23.7%) patients. The all-cause in-hospital mortality rate was 127/576 (20.0%). In the multivariate analysis, patients with headache had a lower risk of mortality (OR: 0.39, 95% CI: 0.17-0.88, p = 0.007). After adjusting for multiple comparisons in a multivariate analysis, variables that were independently associated with a higher odds of having headache in COVID-19 patients were anosmia, myalgia, female sex and fever; variables that were associated with a lower odds of having headache were younger age, lower score on modified Rankin scale, and, regarding laboratory variables on admission, increased C-reactive protein, abnormal platelet values, lymphopenia and increased D-dimer., Conclusion: Headache is a frequent symptom in COVID-19 patients and its presence is an independent predictor of lower risk of mortality in COVID-19 hospitalized patients.

Cerebral venous sinus thrombosis (CVST) is a cause of secondary headache with substantial morbimortality. Headache dominates the clinical presentation, but no typical phenotype has been described. We aim to evaluate the presence of red flags in headache in patients with confirmed CVST at the moment of emergency department (ED) presentation.Retrospective STROBE compliant cohort study including patients with confirmed CVST that consulted because of headache at the ED. We analyzed presence and type of red flags at the moment of consult. We evaluated whether CVST was suspected at the moment of imaging request and analyzed delay in the diagnosis.Nineteen patients fulfilled inclusion and exclusion criteria. Mean age was 48.5 years, 47.4% were female. All the studied patients exhibited at least 1 red flag, being abnormal neurological examination the most frequent (79%), followed by the presence of other neurological symptoms (68%), alarm data related with headache phenotype (63%), or risk factors concerning prior medical history (47%). Temporal pattern of the headache was acute in 42.1%, thunderclap in 31.6%, and subacute in 26.3%. In none patient CVST was the specific suspicion when imaging was requested. Median time since headache onset and ED presentation was 84 hours, being different in patients with associated symptoms (48 hours) when compared with isolated headache patients (168 hours). Time since ED presentation and the diagnosis also differed between the 2 groups, being more prolonged in patients with an isolated headache at presentation.Headache attributed with CVST did not exhibit any distinctive phenotype, but all the patients presented some red flag, being abnormal neurological examination the most frequent.

Objective: To identify possible structural connectivity alterations in patients with episodic and chronic migraine using magnetic resonance imaging data., Methods: Fifty-four episodic migraine, 56 chronic migraine patients and 50 controls underwent T1-weighted and diffusion-weighted magnetic resonance imaging acquisitions. Number of streamlines (trajectories of estimated fiber-tracts), mean fractional anisotropy, axial diffusivity and radial diffusivity were the connectome measures. Correlation analysis between connectome measures and duration and frequency of migraine was performed., Results: Higher and lower number of streamlines were found in connections involving regions like the superior frontal gyrus when comparing episodic and chronic migraineurs with controls ( p  < .05 false discovery rate). Between the left caudal anterior cingulate and right superior frontal gyri, more streamlines were found in chronic compared to episodic migraine. Higher and lower fractional anisotropy, axial diffusivity, and radial diffusivity were found between migraine groups and controls in connections involving regions like the hippocampus. Lower radial diffusivity and axial diffusivity were found in chronic compared to episodic migraine in connections involving regions like the putamen. In chronic migraine, duration of migraine was positively correlated with fractional anisotropy and axial diffusivity., Conclusions: Structural strengthening of connections involving subcortical regions associated with pain processing and weakening in connections involving cortical regions associated with hyperexcitability may coexist in migraine.

Background: White matter alterations have been observed in patients with migraine. However, no microstructural white matter alterations have been found particularly in episodic or chronic migraine patients, and there is limited research focused on the comparison between these two groups of migraine patients., Methods: Fifty-one healthy controls, 55 episodic migraine patients and 57 chronic migraine patients were recruited and underwent brain T1-weighted and diffusion-weighted MRI acquisition. Using Tract-Based Spatial Statistics (TBSS), fractional anisotropy, mean diffusivity, radial diffusivity and axial diffusivity were compared between the different groups. On the one hand, all migraine patients were compared against healthy controls. On the other hand, patients from each migraine group were compared between them and also against healthy controls. Correlation analysis between clinical features (duration of migraine in years, time from onset of chronic migraine in months, where applicable, and headache and migraine frequency, where applicable) and Diffusion Tensor Imaging measures was performed., Results: Fifty healthy controls, 54 episodic migraine and 56 chronic migraine patients were finally included in the analysis. Significant decreased axial diffusivity (p < .05 false discovery rate and by number of contrasts corrected) was found in chronic migraine compared to episodic migraine in 38 white matter regions from the Johns Hopkins University ICBM-DTI-81 White-Matter Atlas. Significant positive correlation was found between time from onset of chronic migraine and mean fractional anisotropy in the bilateral external capsule, and negative correlation between time from onset of chronic migraine and mean radial diffusivity in the bilateral external capsule., Conclusions: These findings suggest global white matter structural differences between episodic migraine and chronic migraine. Patients with chronic migraine could present axonal integrity impairment in the first months of chronic migraine with respect to episodic migraine patients. White matter changes after the onset of chronic migraine might reflect a set of maladaptive plastic changes.

Objectives: This study aimed to explore the views and experiences of a group of Spanish patients suffering from new daily persistent headache (NDPH)., Methods: A qualitative descriptive study was conducted with patients diagnosed with NDPH. Purposeful sampling was performed among patients attending a specialized Headache Unit at 2 university hospitals between February 2017 and December 2018. In total, 18 patients (11 women, 7 men; mean age 45.3, standard deviation 10.6) with a median duration of illness of 70 months (interquartile range, 24-219) were recruited to this study. Data were collected through in-depth interviews, researchers' field notes and patients' drawings. Thematic analysis was used to identify emerging themes., Results: Three main themes were identified: (1) the origin of the illness and seeking answers; (2) characteristics of the pain; and (3) the impact of pain on patients' lives. The patients precisely recalled the time of onset and the trigger of the pain. Pain was constantly present, although it varied in form. At the onset, pain was perceived as a sign of alarm while, over time, it became an invisible illness. The headache commonly had a major impact on everyday life and could cause lifestyle changes. In addition, pain could be emotionally disruptive and could also lead to family estrangement and a search for solitude., Conclusions: Our results provide insight into how NDPH is experienced, which may be helpful in managing NDPH patients. In our cohort, patients identified precipitating events but sought answers regarding the origin of their illness and their pain. Pain was a continuous sensation that had a major impact on patients' daily lives and emotions., (© 2019 American Headache Society.)

Background: Nummular headache is a primary headache characterised by superficial, coin-shaped pain. Superficial sensory fibre dysfunction might be involved in its pathophysiology. Considering the mechanism of action of onabotulinumtoxinA, it could be a reasonable option in treatment of nummular headache. The aim of the study was to evaluate the efficacy and tolerability of onabotulinumtoxinA in a series of nummular headache patients., Patients and Methods: This was an observational, prospective, non-randomized and open-label study. Nummular headache patients with at least 10 headache days in three preceding months were included. They were administered 25 units of onabotulinumtoxinA. The primary endpoint was the decrease of headache days per month, evaluated between weeks 20 to 24, compared with baseline. The secondary endpoints included reduction of intense headache days and acute treatment days evaluated between weeks 20-24 and weeks 8-12, compared with baseline. The 30%, 50% and 75% responder rates were determined, and tolerability described., Results: We included 53 patients, 67.9% females, with a median age of 54 years. Preventive treatment had been used previously in 60.4% of patients. The median diameter of the nummular headache was 5 cm. At baseline, the number of headache days per month was 24.5 (7.3); the number of intense headache days was 12.5 (10.1), and the number of acute treatment days was 12.8 (7.8). After onabotulinumtoxinA, the mean number of headache days per month decreased to 6.9 (9.3) between weeks 20 and 24 ( p  < 0.001). Secondary endpoints concerning intense headache days per month and acute treatment days per month were also statistically significant ( p  < 0.001). The 50% responder rate, evaluated between weeks 20 and 24, was 77.4% and the 75% responder rate was 52.8%. Concerning tolerability, 26 patients (49.1%) experienced an adverse event (AE), the commonest being injection-site pain in 12 cases (22.6%). There were no moderate or severe AEs., Conclusion: It was found that after injecting onabotulinumtoxinA, the number of headache days per month was reduced in nummular headache patients. The number of intense headache days per month and acute treatment days were also lowered. No serious adverse events occurred during treatment.

Background: The occipital neuralgia affects 3 out of every 100,000 people and includes the neuralgia of the greater occipital nerve (GON) and the neuralgia of the minor and third occipital nerves. These nerves emerge from the posterior branches of the first cervical roots, innervate the muscles of the nape, and provide the sensitivity of the scalp. The most frequent issue is not to find causes that justify neuralgia for what is usually idiopathic. The nerve that most often causes neuralgia is the GON that is usually wrongly called Arnold's nerve, so neuralgia is also called Arnold's neuralgia., Methods: We have reviewed the first description of occipital neuralgia., Results: Two Spanish doctors, José Benito Lentijo and Mateo Martínez Ramos, had already described in detail the neuralgia of the GON before Arnold was born. The first clinical case of occipital neuralgia due to GON involvement was published by them in a Spanish medical journal in 1821, and they called it cervico-suboccipital neuralgia., Conclusion: We claim in this article the role of these two Spanish doctors in the history of Neurology.

(1) Background: Spatial changes in pressure sensitivity have been described in migraine and tension-type headaches. Our aim was to determine differences in the spatial distribution of pressure pain sensitivity of the temporalis muscle between cluster headache (CH) patients and headache-free controls; (2) Methods: Pressure pain thresholds (PPTs) were determined over nine points covering the temporalis muscle in 40 men with episodic CH and 40 matched headache-free controls in a blinded fashion. Topographical pressure pain sensitivity maps were constructed based on interpolation of the PPTs. Patients were evaluated in a pain-free period (remission phase), at least 3 months from the last attack and without medication; (3) Results: The analysis of covariance (ANCOVA) found significant difference between points (F = 21.887; P < 0.001) and groups (F = 24.416; P = 0.602), but not between sides (F = 0.440; P = 0.508). No effect of depression (F = 0.014; P = 0.907) or anxiety (F = 0.696; F = 0.407) was observed. A post-hoc analysis revealed: 1) lower PPTs at all points in patients than in controls, 2) an anterior-to-posterior gradient in patients but not in controls, with lower PPTs located in the anterior column. Large between-groups effects were shown in all points (standardized mean difference, SMD > 0.8); (4) Conclusions: Bilateral pressure pain hypersensitivity to pressure pain in the temporalis muscle and an anterior-to-posterior gradient to pressure pain was observed in men with episodic CH.

Objective: Long-term real-life studies have supported a cumulative effect of OnabotulinumtoxinA (OnabotA) for the prophylactic treatment of chronic migraine (CM) during consecutive cycles, and individual adaptations have been described to improve clinical response., Methods: This was a cohort longitudinal retrospective study of consecutive adult patients from the Headache Unit of the Hospital Clínico Universitario de Valladolid and the Hospital Universitario de La Princesa (Madrid) on OnabotA treatment for chronic migraine from May 2012 to December 2017. All patients were followed for 24 weeks. Full-length response to OnabotA was defined as ≥50% reduction in headache days for at least 12 weeks, and wearing off response was defined as a clinical response but with duration shorter than 10 weeks. We have analyzed the incidence and clinical predictors of this wearing off response., Results: A total of 193 patients were included, of whom 91 (47.1%) were considered full-length responders and 45 (23.3%) wearing off responders. No statistically significant clinical predictors (including demographic variables and baseline headache characteristics) of full-length response or wearing off response were detected in our study. An increase in dose during the second treatment cycle was attempted in 68.9% of the wearing off patients, achieving a longer duration of response of up to 12 weeks in 74.2%., Conclusions: Wearing off response to OnabotA during the first treatment cycle is not uncommon in patients with CM. Increasing the dose in subsequent cycles could improve clinical response, but further multicenter long-term studies are needed to establish predictors and solutions to this problem., (© 2019 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

OnabotulinumtoxinA has been demonstrated to be effective as a preventive treatment in patients with chronic migraine (CM). Five years after the approval of onabotulinumtoxinA in Spain, the Headache Study Group of the Spanish Society of Neurology considered it worthwhile to gather a group of experts in treating patients with CM in order to draw up, based on current evidence and our own experience, a series of guidelines aimed at facilitating the use of the drug in daily clinical practice. For this purpose, we posed 12 questions that we ask ourselves as doctors, and which we are also asked by our patients. Each author responded to one question, and the document was then reviewed by everyone. We hope that this review will constitute a practical tool to help neurologists treating patients with CM., (Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Nummular headache (NH) is characterized by continuous or intermittent head pain, which remains confined to a round or oval shaped area of the scalp, generally 1 to 6 cm in diameter. Usually mild or moderate in intensity, some patients suffer severe acute exacerbations or continuous disabling pain. Areas covered: This article reviews epidemiological and clinical features of NH, the most recently proposed pathophysiological mechanisms, and state-of-the-art management according to the literature. Expert commentary: Information regarding true incidence and prevalence is lacking, but NH is a fairly common disorder in patients attending a headache clinic. Diagnostic work-up requires the exclusion of systemic and structural disease by a thorough physical examination, blood tests including immunology screening, and neuroimaging. No clinical trials have been conducted for NH, so the level of evidence for any treatment is low. Gabapentin seems to be the most effective oral medication; subcutaneous injection of the area with onabotulinum toxin type A also seems to be effective, and should be considered as an alternative to gabapentin.

Objective: Previous studies suggest that trigger points (TrPs) contribute to migraine pain, but no data is available on the effects of TrPs on pressure pain sensitivity. Our objective was to investigate the association between the number of TrPs and widespread pressure hypersensitivity in women with episodic migraines., Methods: Ninety-five women with episodic migraines participated. Clinical features of migraines, that is, intensity, duration, frequency, and onset, were collected. Active and latent TrPs were bilaterally explored in the temporalis, masseter, suboccipital, sternocleidomastoid, upper trapezius, and splenius capitis musculature. Pressure pain thresholds (PPTs) were assessed over the trigeminal area (i.e., temporalis muscle), extratrigeminal (i.e., C5/C6 zygapophyseal joint), and a distant pain-free point (i.e., tibialis anterior muscle)., Results: Active TrPs in the temporalis and upper trapezius muscles were the most prevalent. The number of active but not latent TrPs was significantly and negatively associated with PPTs: the higher the number of active TrPs, the lower the widespread PPT and the more generalized sensitization., Conclusions: This study found that the number of active but not latent TrPs in head and neck and shoulder muscles was associated with widespread pressure hypersensitivity in women with episodic migraines, suggesting a potential contribution of active TrPs as contributors for sensitization processes in migraines., (© 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Background: Previous pilot studies suggest the presence of heterogeneous sensitivity to pressure in primary headaches without considering the frequency of headache episodes., Objective: To investigate the differences in topographical pressure pain sensitivity maps in the temporalis muscle between individuals with frequent episodic (FETTH) and chronic (CTTH) tension-type headache by controlling the presence of anxiety and depression., Methods: oPressure pain thresholds (PPTs) were assessed bilaterally from 9 points distributed over the temporalis muscle (3 points in the anterior portion, 3 in the middle portion, and the remaining 3 in the posterior portion of the muscle belly) in 113 patients with FETTH and 91 with CTTH in a blinded design. Topographical pressure pain sensitivity maps based on interpolation of the PPTs were constructed. Clinical features of headache were collected in a 4-week headache diary. Anxiety and depression (Hospital Anxiety and Depression Scale) were also assessed., Results: The multilevel analysis of covariance found significant difference in PPT levels between points (F = 47.649; P < 0.001), but not between groups (F = 0.801; P = 0.602) or sides (F = 0.331; P = 0.565). No significant effect of gender (F = 0.785; P = 0.667), depression (F = 0.515; P = 0.846), or anxiety (F = 0.639; P = 0.745) was observed. Post hoc comparisons revealed: (1) no differences between FETTH and CTTH; (2) no side-to-side differences; and (3) anterior-to-posterior gradient with the most sensitive points located in the anterior column, followed by those located in the central column and the posterior column of the muscle (all, P < 0.001)., Conclusions: This study confirmed an anterior-to-posterior gradient of sensitivity to pressure in both groups, with the highest sensitivity at the anterior part of the muscle. Further, we found similar pressure pain sensitivity in the trigeminal area in people with FETTH or CTTH with no association with depressive or anxiety levels., (© 2017 World Institute of Pain.)

Objective: To investigate differences in topographical pressure pain sensitivity maps of the scalp between patients with migraine and healthy controls considering the chronicity (episodic/chronic) and side (strictly unilateral/bilateral) of the symptoms., Background: It seems that the trigeminal area is sensitized in migraine. No study has investigated topographical pressure sensitivity maps of the scalp in patients with migraine., Methods: Pressure pain thresholds (PPTs) were assessed from 21 points distributed over the scalp in 86 patients with episodic migraine, 76 with chronic migraine, and 42 healthy age and matched healthy controls in a blinded design. Topographical pressure pain sensitivity maps based on interpolation of the PPTs were constructed. Clinical features of migraine, anxiety, and depression (Hospital Anxiety and Depression Scale, HADS) were collected., Results: The multivariate ANCOVA revealed significant differences in PPT between points (F = 55.674; P < .001) and groups (F = 5.316; P = .006), but not sides (F = 0.880; P = .417). No significant effect of gender (F = 0.897; P = .656), depression (F = 1.109; P = .220), or anxiety (F = 0.981; F = 0.569) was found. Post hoc comparisons revealed: (1) lower PPTs in both migraine groups than in healthy controls in all points (P < .001); (2) no significant differences between chronic or episodic migraine (P > .335) except for Fp1 (P = .045) and Fp2 (P = .017) points where subjects with chronic migraine had lower PPTs than those with episodic migraine; (3) no differences between bilateral/unilateral migraine (P > .417). An anterior to posterior gradient was found, with the lowest PPTs located in frontal regions and the highest PPTs in occipital areas (all groups, P < .001)., Conclusions: We found that patients with migraine exhibited generalized pressure pain hypersensitivity in the head as compared to healthy controls and that hypersensitivity was similar between episodic/chronic and unilateral/bilateral migraine. Topographical pressure pain sensitivity maps revealed an anterior to posterior gradient of pressure pain sensitivity in both migraine and control groups., (© 2016 American Headache Society.)

Objective: The aim of the present work is to analyze certain psychological features in a group of patients diagnosed with Epicrania fugax (EF; that has been recently included in the appendix of the International Classification of Headache Disorders, third edition, beta version), as well as their association with diverse demographic and clinical characteristics of the sample., Design: Case-control., Method: Perceived Stress Scale (PSS), Stress Coping (COPE), Big Five Personality Traits (NEO-FFI), Depression (BDI-II), and Trait Anxiety (STAI) were evaluated in 23 patients with EF and 23 matched healthy controls. Differences between EF patients and controls were analyzed using the Mann-Whitney U test. Differences in psychological features as a function of the demographic and clinical characteristics were examined using one-way Analysis of Variance (ANOVA), Mann-Whitney U test, or Pearson's correlations., Results: The two groups differed significantly from each other in Denial, Trait anxiety, and Depression. Low-frequency epicrania patients scored significantly higher than controls in Perceived stress, Neuroticism, Denial, Self-blame, Trait anxiety, and Depression and higher than high-frequency EF in Venting., Conclusions: The results initially suggest the absence of substantial differences between patients suffering of EF and healthy controls. On the contrary, low-frequency EF patients show a distinctive "negative (unhealthy) psychological profile," in opposition to high-frequency EF patients. This circumstance highlights the potential need to consider low- frequency EF patients as a target for psychological intervention in combination with the most common medical procedures. Longitudinal studies are necessary to correctly elucidate the influence of these psychological variables on the course of EF., (© 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Objective: To investigate widespread pressure hyperalgesia in the trigemino-cervical and extra-trigeminal (distant pain-free) regions in women with episodic and chronic migraine., Methods: Fifty-one women with episodic migraine, 52 women with chronic migraine, and 52 healthy women without headache history were recruited. Pressure pain thresholds (PPT) were bilaterally assessed over the trigeminal area (i.e., temporalis muscle), cervical area (i.e., C5/C6 zygapophyseal joint), and two extra-trigeminal areas (i.e., second metacarpal, tibialis anterior muscle) in a blinded design. Clinical features of migraine and anxiety/depression (Hospital Anxiety and Depression Scale, HADS) were also assessed., Results: The multivariate analysis of covariance (ANCOVA) revealed that PPTs were significantly decreased bilaterally over trigeminal and extra-trigeminal points in migraine patients compared to healthy women (all sites, P < 0.001). No differences between episodic and chronic migraine were observed (all, P > 0.919). The presence of neck pain (all, P > 0.282), anxiety (P > 0.425) or depression (all, P > 0.316) did not influence the results. The intensity of migraine pain was negatively associated with widespread pressure pain sensitivity: The greater the intensity of migraine attacks, the lower the widespread PPT levels, i.e., the greater the widespread sensitization., Conclusions: This study found similar widespread pressure hypersensitivity in women with episodic or chronic migraine suggesting that central manifestations are involved both in episodic and chronic migraine., (© 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: We aim to report 4 patients with brief pain paroxysms whose clinical features remind of typical epicrania fugax (EF), except for the direction along a transverse trajectory., Background: EF has been defined as a brief paroxysmal head pain, with stabbing quality, describing a linear or zig-zag trajectory across the surface of one hemicranium., Methods: We considered all patients attending the headache outpatient office at 3 tertiary hospitals from March 2008 to December 2015. We identified a total of 4 cases with dynamic pain paroxysms moving in coronal direction., Results: The mean age at onset was 49 years (range 34-75). All the patients suffered a dynamic pain from parietal or temporal areas to the contralateral ones, crossing the midline in a linear or zig zag trajectory, the entire sequence lasting 2-3 seconds. No triggers were identified. One patient noticed mild interictal tenderness at the stemming point. The frequency of the attacks varied from 2 per week to 1 every 2 months. No underlying disorders were identified by physical and neurological exams and neuroimaging and laboratory tests., Conclusions: Our patients presented with a paroxysmal head pain that might correspond to a transverse variant of EF. These observations may not only expand the EF phenotype but also reinforce the distinction between EF and pericranial neuralgias., (© 2016 American Headache Society.)