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Background Headache is a frequent symptoms of coronavirus disease 2019 (COVID-19). Its long-term evolution remains unknown. We aim to evaluate the long-term duration of headache in patients that presented headache during the acute phase of COVID-19. Methods This is a post-hoc multicenter ambisective study including patients from six different third-level hospitals between 1 March and 27 April 2020. Patients completed 9 months of neurological follow-up. Results We included 905 patients. Their median age was 51 (IQR 45–65), 66.5% were female, and 52.7% had a prior history of primary headache. The median duration of headache was 14 (6–39) days; however, the headache persisted after 3 months in 19.0% (95% CI: 16.5–21.8%) and after 9 months in 16.0% (95% confidence interval: 13.7–18.7%). Headache intensity during the acute phase was associated with a more prolonged duration of headache (Hazard ratio 0.655; 95% confidence interval: 0.582–0.737). Conclusion The median duration of headache was 2 weeks, but in approximately a fifth of patients it became persistent and followed a chronic daily pattern.

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 naive, or not. We analyzed if nonuse of triptans was justified by formal contraindications or adverse events. We assessed if triptan naive 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 naive. 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 naive patients, the presence of contraindications, frequency of vascular risk factors, and differences in management prior to the referral to a headache unit.

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.

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).

Background The presence of headache during the acute phase of COVID-19 could be associated with the innate response and the cytokine release. We aim to compare the cytokine and interleukin profile in hospitalized COVID-19 patients at the moment of admission with and without headache during the course of the disease. Methods An observational analytic study with a case control design was performed. Hospitalized patients from a tertiary hospital with confirmed COVID-19 disease were included. Patients were classified into the headache or the control group depending on whether they presented headache not better accounted for by another headache disorder other than acute headache attributed to systemic viral infection. Several demographic and clinical variables were studies in both groups. We determined the plasmatic levels of 45 different cytokines and interleukins from the first hospitalization plasma extraction in both groups. Results One hundred and four patients were included in the study, aged 67.4 (12.8), 43.3% female. Among them, 29 (27.9%) had headache. Patients with headache were younger (61.8 vs. 69.5 years, p = 0.005) and had higher frequency of fever (96.6 vs. 78.7%, p = 0.036) and anosmia (48.3% vs. 22.7%, p = 0.016). In the comparison of the crude median values of cytokines, many cytokines were different between both groups. In the comparison of the central and dispersion parameters between the two groups, GROa, IL-10, IL1RA, IL-21, IL-22 remained statistically significant. After adjusting the values for age, sex, baseline situation and COVID-19 severity, IL-10 remained statistically significant (3.3 vs. 2.2 ng/dL, p = 0.042), with a trend towards significance in IL-23 (11.9 vs. 8.6 ng/dL, p = 0.082) and PIGF1 (1621.8 vs. 110.6 ng/dL, p = 0.071). Conclusions The higher levels of IL-10 -an anti-inflammatory cytokine- found in our sample in patients with headache may be explained as a counteract of cytokine release, reflecting a more intense immune response in these patients.

Background Nummular headache (NH) is defined in the International Classification of Headache Disorders (ICHD) by the presence of localized pain circumscribed to a small round area of the scalp, not better accounted by any other diagnosis. As in many other primary headache disorders, secondary cases might occur. To date, 13 secondary cases have been published. We aim to present a long series of secondary NH and review the literature of symptomatic NH. Patients and methods Retrospective analysis of an observational prospective cohort in a headache unit located in a tertiary hospital. We included patients that fulfilled ICHD criteria and were attributed to a secondary cause. We describe the clinical characteristics, the underlying causes, and the response to treatment. Results We included 274 NH patients; eight of them (2.9%) were considered secondary. In one patient the underlying cause was subcutaneous, as for six cases the lesion was located in the bone (two hemangiomas, one osteoma, three different types of cysts), and in one was intracranial but closely related with internal diploe (cavernoma). Among our patients with secondary NH, a preventive therapy was not always needed and, when required, gabapentin or onabotulinumtoxinA were used with positive response. Conclusions Secondary NH phenotype overlaps primary NH. Therefore, we recommend routine imaging study in every NH patient. Concerning treatment, it was not necessary to remove the underlying lesion to control the pain and many cases responded to the same prophylactics as primary NH cases.

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.

[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.

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 headache red flags were present in most cases. There was not any universal red flag, being necessary the comprehensive evaluation of all of them.

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.

Background Triptanophobia is the excessive and inadequately justified concern about the potential risks of triptans. In this study we evaluate the possible causes of non-use of triptans in chronic migraine patients and the possible consequences. Results We included 941 patients, 86.2% female with a mean age of 39.9 years. Mean number of headache days per month was 24.1. The number of patients using triptans was 247 (26.2%). Triptans had been discontinued due to adverse events in 116 patients (12.3%), so 578 patients (61.4%) were triptan naïve. Formal contraindications were found in 23 patients (2.4%). Frequency of vascular risk factors, contraceptive use or age did not differ between the groups (p > 0.1). Participants with triptans used symptomatic medication fewer days per month (13.9 vs. 17.1, p

Supplemental material, sj-pdf-1-cep-10.1177_0333102420965146 for Phenotypic characterization of acute headache attributed to SARS-CoV-2: An ICHD-3 validation study on 106 hospitalized patients by Javier Trigo López, David García-Azorín, Álvaro Planchuelo-Gómez, Cristina García-Iglesias, Carlos Dueñas-Gutiérrez and Ángel L Guerrero in Cephalalgia

Objective Cranial pain is a condition that has a negative impact on human lives, and occipital neuralgia is among its causes. This study aims to evaluate the clinical characteristics and therapeutic results of a series of patients with occipital neuralgia. Design Prospective registry (observational study). Settings Headache outpatient clinic in a tertiary hospital. Subjects Sixty-eight cases. Methods Demographic and nosological characteristics have been analyzed, as well as treatment response of occipital neuralgia. All patients were recruited between January 2008 and January 2018, and the diagnosis of occipital neuralgia was made according to the International Headache Society (International Classification of Headache Disorders) criteria being utilized at the time of diagnosis. Results Sixty-eight patients were diagnosed with occipital neuralgia, which corresponded to 1.2% of the total number of patients (5,515) who visited our Headache Unit during the aforementioned period. Fifty-four (79.4%) of them were female. Baseline pain was present in 62 (91.1%) patients, and exacerbations in 42 (61.8%). Latency from onset (range) was 27.7 ± 56.1 (1–360) months. Conclusions Occipital neuralgia is an uncommon disorder in the sample explored. The prolonged latency between the onset of symptoms and diagnosis suggests that there should be an increased awareness of this disorder.

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 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 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.

Resumen Fundamento y objetivo La encefalitis limbica (EL) asociada a anticuerpos contra canales de potasio dependientes de voltaje (Ac-CKDV) es una entidad de reciente descripcion, en general no asociada a cancer y con buena respuesta al tratamiento inmunodepresor. Describimos las caracteristicas clinicas, radiologicas y el perfil evolutivo de una serie de pacientes en nuestro medio. Pacientes y metodo Analisis retrospectivo de variables demograficas, clinicas y evolutivas de una serie de pacientes con EL con Ac-CKDV y ausencia de anticuerpos onconeuronales. Resultados En un periodo de 10 anos se identificaron 13 pacientes; el 77% fueron varones y la mediana de edad de 67 anos (extremos 50–75). La mediana de presentacion fue de 10 semanas (extremos 1–24 semanas). Todos presentaron alteracion de la memoria episodica, un 77% crisis epilepticas y un 77% sindrome confusional o alteracion de la conducta. Un trastorno de conducta sueno-REM (TCSR) se detecto en 9 pacientes interrogados. La resonancia magnetica (RM) fue anormal en el 84,6%, el electroencefalograma (EEG) en el 91%, el liquido cefalorraquideo (LCR) en el 60% y se detecto hiponatremia en el 83% de los casos. Todos los pacientes recibieron tratamiento con inmunoglobulinas y/o glucocorticoides y el 61,5% quedo asintomatico o con sintomas minimos. Tras un seguimiento mediano de 24 meses (extremos 3–108 meses) ningun paciente desarrollo cancer. Conclusiones Las caracteristicas demograficas y clinicas de nuestra serie son similares a las ya publicadas y se confirma que se trata de una entidad con buena respuesta al tratamiento. La presentacion cronica y la normalidad de la RM no descarta el diagnostico sindromico y en estos casos la existencia de un TCSR, hiponatremia o un LCR inflamatorio resultan de especial ayuda diagnostica.