Evaluation of the concomitant use of prophylactic treatments in patients with migraine under anti-calcitonin gene-related peptide therapies: The PREVENAC study.

BACKGROUND AND PURPOSE: Anti-calcitonin gene-related peptide (CGRP) therapies are recent preventive therapies approved for both episodic and chronic migraine. One of the measures of effectiveness is the withdrawal of other preventive treatments. The objective of this study is to quantify the impact of anti-CGRP drugs in concomitant preventive treatment in patients with migraine. METHODS: This was an observational, retrospective, multicenter cohort study with patients from nine national headache units. Patients with migraine undergoing treatment for at least 6 months with anti-CGRP antibodies, who were initially associated with some preventive treatment (oral and/or onabotulinumtoxinA) were included. Demographic and clinical variables were collected, as well as variables related to headache. Differences according to withdrawal or nonwithdrawal were evaluated. RESULTS: A total of 408 patients were included, 86.52% women, 48.79 (SD = 1.46) years old. Preventive treatment was withdrawn in 43.87% (179/408), 20.83% partially and 23.04% totally. In 27.45% (112/408), it was maintained exclusively due to comorbidity and in 28.6% (117/408) due to partial efficacy. The most frequent time of withdrawal was between 3 and 5 months after the start of treatment. The baseline characteristics associated with nonwithdrawal were comorbidities: insomnia, hypertension and obesity, chronic migraine, and medication overuse. In the multivariate analysis, the absence of high blood pressure, a greater number of preventive treatments at the start, and a lower number of migraine days/month after anti-CGRP treatment were independently associated with withdrawal of the treatment (p < 0.05). CONCLUSIONS: Anti-CGRP antibodies allow the withdrawal of associated preventive treatment in a significant percentage of patients, which supports its effectiveness in real-life conditions.

Effectiveness, tolerability, and response predictors of preventive anti-CGRP mAbs for migraine in patients over 65 years old: a multicenter real-world case-control study.

OBJECTIVE: To evaluate clinical characteristics, effectiveness, and tolerability of preventive anti- calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) in the elderly. Anti-CGRP mAbs have demonstrated efficacy and safety in patients with migraine although there is limited information regarding the elderly. DESIGN: We performed a multicenter case-control study of cases (patients over 65 years old) and controls (sex-matched patients under 55 years old) with migraine receiving anti-CGRP mAbs. METHODS: We included the demographic characteristics, effectiveness-reduction in the number of monthly headache days (MHD) and monthly migraine days (MMD), 30%, 50%, and 75% responder rates-and treatment emergent adverse events (TEAEs). The primary endpoint was the 50% response rate regarding MHD at weeks 20-24; exploratory 50% response predictors in the elderly were evaluated. RESULTS: In total, 228 patients were included: 114 cases , 114 controls-. Among cases 84.2% (96/114) were women, 79.8% (91/114) CM; mean age of cases 70.1 years old (range: 66-86); mean age of controls was 42.9 years old(range: 38-49). Cases had a higher percentage of vascular risk factors (P < .05),older age of onset (P < .001) and more reported prior preventive treatments (P < .001). Regarding effectiveness in cases, 50% response rate was achieved by 57.5% (42/73) at 20-24 weeks, with lower reduction in the MHD at 8-12 weeks (5 [7.2], 8 [9.1]; P = .001) and a higher reduction in MMD at 20-24 weeks (10.7 [9.1], 9.2 [7.7]; P = .04) compared to the control group. The percentage of TEAEs was similar in the 2 groups. Diagnosis of episodic migraine (EM) (P = .03) and lower number of MHD at baseline (P = .001) were associated with a 50% response in the elderly in univariate analysis. CONCLUSIONS: Our study provides real world evidence of effectiveness and safety of anti-CGRP mAbs for migraine in patients without upper age-limit and possible predictors of anti-CGRP response in the elderly.

Real-World Evaluation of the Tolerability to Onabotulinum Toxin A: The RETO Study.

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.

Amitriptyline for post-COVID headache: effectiveness, tolerability, and response predictors.

BACKGROUND: Headache is one of the most frequently reported symptoms in post-COVID patients. The clinical phenotype of COVID-19 headache combines phenotypic features of both tension-type headache (TTH) and migraine. We aimed to assess the effectiveness, side effects and predictors of amitriptyline (AMT) response in a real-world study setting. METHODS: We performed an observational multicentric study with a retrospective cohort. All consecutive patients with confirmed COVID-19 infection who received AMT for post-COVID headache from March 2020 to May 2021 were included. Response was evaluated by the reduction in the number of headache days per month (HDM) between weeks 8 and 12, compared with the baseline. We explored which variables were associated with a higher probability of response to AMT. RESULTS: Forty-eight patients were eligible for the study, 40/48 (83.3%) females, aged 46.85 (SD: 13.59) years. Patients had history of migraine 15/48 (31.3%) or TTH 5/48 (10.4%). The mean reduction of HDM was 9.6 (SD: 10.9; 95% CI 6.5, 12.7) days. Only 2/48 (5%) of patients discontinued AMT due to poor tolerability. History of TTH (10.9, 95% CI 1.3, 20.6) and nausea (- 8.5, 95% CI - 14.6, - 2.5) were associated with AMT response. CONCLUSIONS: This study provides real-world evidence of the potential benefit of AMT in patients with post-COVID-19 headache, especially in patients with history of TTH and without concomitant nausea.

Machine-learning-based approach for predicting response to anti-calcitonin gene-related peptide (CGRP) receptor or ligand antibody treatment in patients with migraine: A multicenter Spanish study.

BACKGROUND AND PURPOSE: Several variables have been reported to be associated with anti-calcitonin gene-related peptide (CGRP) receptor or ligand antibody response, but with differing results. Our objective was to determine whether machine-learning (ML)-based models can predict 6-, 9- and 12-month responses to anti-CGRP receptor or ligand therapies among migraine patients. METHODS: We performed a multicenter analysis of prospectively collected data from patients with migraine receiving anti-CGRP therapies. Demographic and clinical variables were collected. Response rates in the 30% to 50% range, or at least 30%, in the 50% to 75% range, or at least 50%, and response rate of at least 75% regarding the reduction in the number of headache days per month at 6, 9 and 12 months were calculated. A sequential forward feature selector was used for variable selection and ML-based predictive models for the response to anti-CGRP therapies at 6, 9 and 12 months, with model accuracy not less than 70%, were generated. RESULTS: A total of 712 patients were included, 93% were women, and the mean (SD) age was 48 (11.6) years. Eighty-four percent of patients had chronic migraine. ML-based models using headache days/month, migraine days/month and the Headache Impact Test (HIT-6) yielded predictions with an F1 score range of 0.70-0.97 and an area under the receiver-operating curve score range of 0.87-0.98. SHAP (SHapley Additive exPlanations) summary plots and dependence plots were generated to evaluate the relevance of the factors associated with the prediction of the above-mentioned response rates. CONCLUSIONS: Our results show that ML models can predict anti-CGRP response at 6, 9 and 12 months. This study provides a predictive tool that can be used in a real-world setting.

Patients and general practitioners assessment of the main outcomes employed in the acute and preventive treatment of migraine: a cross sectional study.

BACKGROUND: We aim to describe and compare patients and general practitioners' opinions about the different variables related to acute and preventive treatment for migraine. PATIENTS AND METHODS: An observational descriptive study was performed. Patients with episodic migraine and general practitioners, from our healthcare area, were invited to answer a survey about the different variables related to migraine treatment. They were asked for their opinions on the different variables, and to consider the desired efficacy in percentage terms and the desired action times of treatment. RESULTS: Fifty-five patients and fifty-five general practitioners were selected. Effectiveness was considered the most important variable for symptomatic and preventive treatment. Cost was considered the least important variable. Patients desired percentage of efficacy was 84.0% (±16.7%) for symptomatic treatment and 79.9% (±17.1%) for preventive treatment. General practitioners desired percentage of efficacy was 75.0% (±14.0) for symptomatic treatment and 70.4% (±14.3) for preventive treatment. For symptomatic treatment the desired action time for pain cessation was selected as 27.5 min (±13.8) for patients and 24.0 min (±18.3) for GPs. For preventive treatment the desired action time for effect was 7.1 days (±4.5) for patients and 13.9 days (±8.9) for general practitioners. CONCLUSION: The most important endpoints were, for acute: effectiveness, a short action time and a persistent effect. For prophylactic: effectiveness, sustained effect and tolerability. Both patients and general practitioners agreed on the most and least preferred endpoints. Desired percentage of efficacy was above 75% for both symptomatic and preventive treatment; and the desired action time was below 30 min for acute treatment and 2 weeks for preventive treatment.

Daily Headache in Chronic Migraine Is a Predictive Factor of Response in Patients Who Had Completed Three Sessions of OnabotulinumtoxinA.

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.

Frequency and phenotype of headache in covid-19: a study of 2194 patients.

To estimate the frequency of headache in patients with confirmed COVID-19 and characterize the phenotype of headache attributed to COVID-19, comparing patients depending on the need of hospitalization and sex, an observational study was done. We systematically screened all eligible patients from a reference population of 261,431 between March 8 (first case) and April 11, 2020. A physician administered a survey assessing demographic and clinical data and the phenotype of the headache. During the study period, 2194 patients out of the population at risk were diagnosed with COVID-19. Headache was described by 514/2194 patients (23.4%, 95% CI 21.7-25.3%), including 383/1614 (23.7%) outpatients and 131/580 (22.6%) inpatients. The headache phenotype was studied in detail in 458 patients (mean age, 51 years; 72% female; prior history of headache, 49%). Headache was the most frequent first symptom of COVID-19. Median headache onset was within 24 h, median duration was 7 days and persisted after 1 month in 13% of patients. Pain was bilateral (80%), predominantly frontal (71%), with pressing quality (75%), of severe intensity. Systemic symptoms were present in 98% of patients. Headache frequency and phenotype was similar in patients with and without need for hospitalization and when comparing male and female patients, being more intense in females.Trial registration: This study was supported by the Institute of Health Carlos III (ISCIII), code 07.04.467804.74011 and Regional Health Administration, Gerencia Regional de Salud, Castilla y Leon (GRS: 2289/A/2020).

Linear Headache: A Novel Entity or a Variant of Nummular Headache? Clinical Characteristics and Treatment Response in a Series of 16 Patients.

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.

Neurological symptoms in Covid-19 patients in the emergency department.

BACKGROUND: Coronavirus disease 2019 (Covid-19) might present neurological symptoms. We aimed to evaluate the frequency of them at the moment of emergency department (ED) visit and their impact in the prognosis. METHODS: Retrospective cohort study including all consecutive hospitalized cases between March 8th and April 11th, 2020. Covid-19 diagnosis was confirmed by polymerase chain reaction test and/or serology. We compared, in patients with and without neurological symptoms on admission, demographic, clinical presentation, and frequency and type of abnormal laboratory values. We analyzed the variables that were associated with in-hospital all-cause mortality by Cox-regression log-rank test. RESULTS: We included 576 hospitalized patients, 250 (43.3%) female, aged 67.2 years. At the moment of ED visit, 320 (55.6%) described neurological symptoms, including anosmia (146, 25.3%), myalgia (139, 24.1%), headache (137, 23.8%), and altered mental status (98, 17.0%). Neurological symptoms started the first symptomatic day in 198 (54.2%) cases. Patients with neurological symptoms presented later to the ED (7.9 versus. 6.6 days, p = .019). Only four (0.6%) cases had no typical Covid-19 general symptoms, and only six (1.9%) had a normal laboratory results, for a sensitivity of 98.7% (95% confidence interval (CI): 96.6%-99.6%) and 98.1% (95% CI: 95.7%-99.2%), respectively. In the multivariate Cox-regression of mortality predictors, anosmia (HR: 0.358, 95%CI: 0.140-0.916) and altered mental status (HR: 1.867, 95%CI: 1.162-3.001) were significant. CONCLUSION: Neurological symptoms were the most frequent extrapulmonary symptoms. They were present in half of the Covid-19 patients at the time of the ED visit. Anosmia on admission was an independent predictor of lower in-hospital mortality and altered mental status on admission predicted in-hospital mortality.

Real world effectiveness and tolerability of candesartan in the treatment of migraine: a retrospective cohort study.

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.

Migraña crónica con cefalea diaria. Revisión de la bibliografía / Chronic migraine with daily headache. Literature review

INTRODUCCIÓN: A pesar de suponer un número no desdeñable de casos, los pacientes con migraña crónica y cefalea diaria son frecuentemente excluidos de los grandes ensayos clínicos terapéuticos. Estos individuos apenas han sido estudiados en la bibliografía y podrían presentar características específicas. DESARROLLO: Un tercio de los pacientes con migraña crónica podría sufrir cefalea todos los días del mes, lo que supone hasta un 1,7-3,3% de los pacientes atendidos en una consulta de neurología general. Al ser excluidos de la mayor parte de los estudios, apenas hay información sobre sus características clínicas y respuesta al tratamiento, y pueden tener una historia de migraña más prolongada y una diferente respuesta al tratamiento. Los pacientes con migraña crónica y cefalea diaria podrían presentar mecanismos fisiopatológicos complejos que favorezcan la manifestación diaria de la migraña. El manejo de estos pacientes es un reto terapéutico, y se ha propuesto la utilidad de la onabotulinumtoxinA. CONCLUSIONES: Los pacientes con migraña crónica y cefalea diaria pueden presentar características clínicas y terapéuticas específicas. Nuevos estudios podrían llevar a plantear su consideración diferenciada de la migraña crónica

INTRODUCTION: Despite representing a significant number of cases, patients with chronic migraine and daily headache are frequently excluded from large therapeutic clinical trials. These individuals have hardly been studied and could have specific properties. Body. A third of patients with chronic migraine may suffer from headaches every day, representing up to 1.7 - 3.3% of patients in a general neurology consultation. These patients are excluded from most studies, so little information is available. They may have a longer lasting migraine and different response to treatment. Patients with chronic migraine and daily headache may have complex pathophysiological mechanisms that favor the daily manifestation of migraine. The management of these patients is a therapeutic challenge, and OnabotulinumtoxinA may be useful. CONCLUSION: Patients with chronic migraine and daily headache may have specific clinical and therapeutic characteristics. New studies could lead to differentiate it from chronic migraine

Triptanophobia in migraine: A case-control study on the causes and consequences of the nonuse of triptans in chronic migraine patients.

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.

Anosmia is associated with lower in-hospital mortality in COVID-19.

BACKGROUND: Anosmia is common in Coronavirus disease 2019, but its impact on prognosis is unknown. We analysed whether anosmia predicts in-hospital mortality; and if patients with anosmia have a different clinical presentation, inflammatory response, or disease severity. METHODS: Retrospective cohort study including all consecutive hospitalized patients with confirmed Covid-19 from March 8th to April 11th, 2020. We determined all-cause mortality and need of intensive care unit (ICU) admission. We registered the first and worst laboratory parameters. Statistical analysis was done by multivariate logistic and linear regression. RESULTS: We included 576 patients, 43.3% female, and aged 67.2 years in mean. Anosmia was present in 146 (25.3%) patients. Patients with anosmia were more frequently females, younger and less disabled and had less frequently hypertension, diabetes, smoking habit, cardiac and neurological comorbidities. Anosmia was independently associated with lower mortality (OR: 0.180, 95% CI: 0.069-0.472) and ICU admission (OR: 0.438, 95% CI: 0.229-0.838, p = 0.013). In the multivariate analysis, patients with anosmia had a higher frequency of cough (OR: 1.96, 95%CI: 1.18-3.28), headache (OR: 2.58, 95% CI: 1.66-4.03), and myalgia (OR: 1.74, 95% CI: 1.12-2.71). They had higher adjusted values of hemoglobin (+0.87, 95% CI: 0.40-1.34), lymphocytes (+849.24, 95% CI: 157.45-1541.04), glomerular filtration rate (+6.42, 95% CI: 2.14-10.71), and lower D-dimer (-4886.52, 95% CI: -8655.29-(-1117.75)), and C-reactive protein (-24.92, 95% CI: -47.35-(-2.48)). CONCLUSIONS: Hospitalized Covid-19 patients with anosmia had a lower adjusted mortality rate and less severe course of the disease. This could be related to a distinct clinical presentation and a different inflammatory response.

Frequency and Type of Red Flags in Patients With Covid-19 and Headache: A Series of 104 Hospitalized Patients.

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.

Neurological Comorbidity Is a Predictor of Death in Covid-19 Disease: A Cohort Study on 576 Patients.

Introduction: Prognosis of Coronavirus disease 2019 (Covid-19) patients with vascular risk factors, and certain comorbidities is worse. The impact of chronic neurological disorders (CND) on prognosis is unclear. We evaluated if the presence of CND in Covid-19 patients is a predictor of a higher in-hospital mortality. As secondary endpoints, we analyzed the association between CND, Covid-19 severity, and laboratory abnormalities during admission. Methods: Retrospective cohort study that included all the consecutive hospitalized patients with confirmed Covid-19 disease from March 8th to April 11th, 2020. The study setting was Hospital Clínico, tertiary academic hospital from Valladolid. CND was defined as those neurological conditions causing permanent disability. We assessed demography, clinical variables, Covid-19 severity, laboratory parameters and outcome. The primary endpoint was in-hospital all-cause mortality, evaluated by multivariate cox-regression log rank test. We analyzed the association between CND, covid-19 severity and laboratory abnormalities. Results: We included 576 patients, 43.3% female, aged 67.2 years in mean. CND were present in 105 (18.3%) patients. Patients with CND were older, more disabled, had more vascular risk factors and comorbidities and fewer clinical symptoms of Covid-19. They presented 1.43 days earlier to the emergency department. Need of ventilation support was similar. Presence of CND was an independent predictor of death (HR 2.129, 95% CI: 1.382-3.280) but not a severer Covid-19 disease (OR: 1.75, 95% CI: 0.970-3.158). Frequency of laboratory abnormalities was similar, except for procalcitonin and INR. Conclusions: The presence of CND is an independent predictor of mortality in hospitalized Covid-19 patients. That was not explained neither by a worse immune response to Covid-19 nor by differences in the level of care received by patients with CND.

Factors associated with the presence of headache in hospitalized COVID-19 patients and impact on prognosis: a retrospective cohort study.

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.

Observational, open-label, non-randomized study on the efficacy of onabotulinumtoxinA in the treatment of nummular headache: The pre-numabot study.

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.

Clinical characteristics of nummular headache and differentiation between spontaneous and posttraumatic variant: an observational study.

BACKGROUND: Head trauma has been described as a precipitating event in Nummular Headache (NH). We aimed to describe the largest NH published series and compare characteristics between idiopathic and post-traumatic cases. METHODS: Patients attended in a Headache Unit in a tertiary hospital (January 2008-January 2018). NH diagnosed according to International Classification of Headache Disorders (ICHD) criteria. We prospectively considered clinical and epidemiological data, comparing idiopathic cases with those precipitated by a cranial trauma. RESULTS: We included 225 patients (145 women, 80 men) with NH. Median latency between onset and diagnosis was 10 months (IQR: 5-24). Symptomatic treatment was used in 190 patients (84.4%) among which 142 (74.7%) experienced response to it. Preventive treatment was necessary in 127 patients (51.4%), among which 95 (74.8%) achieved response. 29 patients (23 women, 6 men) described a head trauma related to beginning of pain. When comparing groups with or without previous trauma, age of onset was higher among post-traumatic patients (59.9 ± 17.4 vs 48.1 ± 18 years, p: 0.001). Allodynia upon palpation was encountered more frequently in trauma triggered painful areas (53.3% vs. 32.7%, p: 0.02). No other clinical characteristics differences were observed. CONCLUSION: Cranial trauma is not a rare trigger of NH. Patients with post-traumatic forms are older and the presence of allodynia is more frequent.

[Eugenics and anarchism in early libertarian neo-Malthusianism in Barcelona, 1896-1915]. / Eugenesia y anarquismo en el primer neomalthusianismo libertario barcelonés, 1896-1915.

Anarchist neo-Malthusianism is increasingly receiving historiographical attention. This article deals with the following question: Did early anarchist neo-Malthusianism in Barcelona have anything to do with eugenics? To what extent, and how? To answer this, the article examines the transnational nature of the anarchist movement, in which cities played an essential role. This is shown in the strong connection between the Barcelona group and the French one, which had inherited the teachings of Paul Robin. The article's thesis is that, although neo-Malthusianism and anarchism were different movements, the fact that they shared the goal of regenerating the species allows us to establish points of contact between them, even though the anarchists formally rejected eugenics on occasion.

El neomalthusianismo anarquista está recibiendo una creciente atención historiográfica. El artículo pretende abordar la siguiente pregunta: ¿Tuvo algo que ver el primer neomalthusianismo anarquista barcelonés con la eugenesia? ¿Hasta qué punto y cómo? Para responder a ello el artículo tiene en cuenta el carácter transnacional del movimiento anarquista en el que las ciudades ocupaban un lugar esencial. Cosa que se materializaba en la fuerte conexión entre el grupo barcelonés y el francés, heredero de las enseñanzas de Paul Robin. La tesis del artículo es que, aunque el neomalthusianismo y el anarquismo eran movimientos distintos, el hecho de que se comparta el objetivo de regenerar la especie permitía establecer puntos de contacto aun cuando ocasionalmente los anarquistas rechazaran formalmente a la eugenesia.