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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.

Objective/background The great auricular nerve (GAN) is a major sensory branch of the cervical plexus. Painful great auricular neuropathy causes pain circumscribed to the inferior preauricular region, the jaw angle, the ventral pinna, and the mastoid region. Methods We present a 46-year-old woman experiencing facial pain in the bilateral preauricular and infra-auricular region, constant, of abrasive quality without any other associated symptomatology that is triggered or aggravated with cephalic movements, cervical turn, mandibular movement, and palpation on the affected area. Results Symptomatic treatment with analgesics, anti-inflammatories, and neuropathic preventive medications was ineffective. However, nerve block anesthetic treatment resulted in complete pain remission. Conclusion Great auricular neuropathy is an uncommon cause of facial pain; our case report is the first bilateral occurrence reported to date. It should be suspected in patients with circumscribed shooting or lancinating paroxysmal pain in the territory of the GAN. It is characterized by the aggravation of pain with cervical movements and complete relief after anesthetic blockade.

Background The COVID-19 pandemic leads to disruptions of health services worldwide. To evaluate the particular impact on neurological services a rapid review was conducted. Methods Studies reporting the provision of neurological services during the pandemic and/or adopted mitigation strategies were included in this review. PubMed and World Health Organization’s (WHO) COVID-19 database were searched. Data extraction followed categories used by WHO COVID-19 pulse surveys and operational guidelines on maintaining essential health services during COVID-19. Findings The search yielded 1101 articles, of which 369 fulfilled eligibility criteria, describing data from 210,419 participants, being adults (81%), children (11.4%) or both (7.3%). Included articles reported data from 105 countries and territories covering all WHO regions and World Bank income levels (low income: 1.9%, lower middle: 24.7%, upper middle: 29.5% and high income; 44.8%). Cross-sectoral services for neurological disorders were most frequently disrupted (62.9%), followed by emergency/acute care (47.1%). The degree of disruption was at least moderate for 75% of studies. Travel restrictions due to lockdowns (81.7%) and regulatory closure of services (65.4%) were the most commonly reported causes of disruption. Authors most frequently described telemedicine (82.1%) and novel dispensing approaches for medicines (51.8%) as mitigation strategies. Evidence for the effectiveness of these measures is largely missing. Interpretation The COVID-19 pandemic affects all aspects of neurological care. Given the worldwide prevalence of neurological disorders and the potential long-term neurological consequences of COVID-19, service disruptions are devastating. Different strategies such as telemedicine might mitigate the negative effects of the pandemic, but their efficacy and acceptability remain to be seen.

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. Supplementary Information The online version contains supplementary material available at 10.1007/s10072-021-05180-8.

Headache disorders are the most prevalent neurological conditions in the Sub-Saharan Africa and the second cause of disability. In this study, we analyze the knowledge about headache disorders and their management among Cameroonian healthcare providers. We conducted an interventional study with a prospective cohort design. Cameroonian health care providers from the whole country were invited. The evaluation was based on a questionnaire that was done before and after a 4-day educational course. The study included 42 participants, 52.4% female, aged 36.8 years. Participants treated a median of 240 monthly patients. Headache was reported as the most frequent neurological condition in their clinics (34%). Mean number of neurological patients seen per week was 69.3, among them 20 were headache patients. At baseline, only 35.8% correctly mentioned at least one primary headache, increasing to 78.6% after the course (p = 0.002). Secondary headaches were correctly identified by 19.0% at baseline and 40.5% after the course (p = 0.01). Clinical history was considered sufficient for headache diagnosis by 57.1% before and 78.6% after (p = 0.5). Correct red flags were mentioned at baseline by only 14.3% of participants, increasing to 40.5% after the course (p = 0.005). At baseline, the preferred symptomatic was paracetamol (47.6%) and Non-Steroidal Anti-Inflammatory Drugs (9.5%), changing to 23.8 and 66.7% after the course (p = 0.05 and

Introduction: Epilepsy is especially prevalent in developing countries: incidence and prevalence rates are at least twice as high as in our setting. Epilepsy is also highly stigmatised, and few resources are available for its management. Material and methods: We performed a descriptive observational study in December 2016, distributing a questionnaire on epilepsy management to healthcare professionals from 3 different hospitals in Cameroon. Data are presented as means or percentages. Results: Thirty-eight healthcare providers participated in the survey; 42.1% were female and mean age was 40.1 years (range, 22-62). Regarding the causes of epilepsy, 68.4% considered it a psychiatric condition, 34.2% a degenerative disease, 28.9% a hereditary condition, and 21.1% secondary to infection. In terms of management, 23.7% considered that thorough clinical history is sufficient to establish a diagnosis. Only 60.5% considered the clinical interview to be important for diagnosis, 52.6% considered EEG to be necessary, and 28.9% considered laboratory analyses to be important. Only 13.2% mentioned neuroimaging. In the treatment of pregnant women, 36.8% recommended folic acid supplementation, 65.8% believed antiepileptic treatment should be maintained, and only 39.5% recommended breastfeeding. Concerning treatment, the participants knew a mean of 2 antiepileptic drugs: phenobarbital was the best known (81.6%), followed by carbamazepine (55.3%) and valproic acid (28.9%). Conclusions: There is a need among healthcare professionals for education and information on the disease, its diagnosis, and management options, in order to optimise management and consequently improve patients’ quality of life. Resumen: Introducción: La epilepsia es una enfermedad prevalente en países en vías de desarrollo debido al mayor número de causas que pueden producirla, al menos duplicándose tanto incidencia como prevalencia en comparación con nuestro medio. Además, existe una gran estigmatización y los medios para su manejo son limitados. Material y métodos: Estudio observacional descriptivo mediante la realización de un cuestionario a profesionales sanitarios de 3 hospitales de Camerún, interrogando sobre factores relacionados con el manejo de la epilepsia, en diciembre de 2016. Se presentan los datos como media o porcentaje. Resultados: Participaron 38 profesionales sanitarios, de los cuales 42,1% eran mujeres, con una edad media de 40,1 años (rango 22-62). Respecto a la causa de la enfermedad, un 68,4% la considera psiquiátrica, 34,2% degenerativa, 28,9% hereditaria y 21,1% secundaria a una infección. En cuanto al manejo, un 23,7% consideraba suficiente la anamnesis para llegar al diagnóstico. Sólo un 60,5% consideraba la historia importante en el diagnóstico, 52,6% consideraba necesario un EEG, un 28,9% creía importantes las pruebas de laboratorio y un 13,2% la neuroimagen. Durante el embarazo, sólo un 36,8% considera importante asociar ácido fólico, sólo el 65,8% cree que hay que mantener el tratamiento y sólo un 39,5% creía recomendable la lactancia. Acerca del conocimiento de antiepilépticos, el número medio de fármacos conocido era de 2, siendo el más conocido el fenobarbital (81,6%) seguido de carbamacepina (55,3%) y ácido valproico (28,9%). Conclusiones: La educación y la mejor información sobre la enfermedad, su diagnóstico y las opciones de manejo son necesarias en los profesionales sanitarios para optimizar el manejo y con ello la calidad de vida de los pacientes.

No specific migraine biomarkers have been found in single‐modality MRI studies. We aimed at establishing biomarkers for episodic and chronic migraine using diverse MRI modalities. We employed canonical correlation analysis and joint independent component analysis to find structural connectivity abnormalities that are related to gray matter morphometric alterations. The number of streamlines (trajectories of estimated fiber‐tracts from tractography) was employed as structural connectivity measure, while cortical curvature, thickness, surface area, and volume were used as gray matter parameters. These parameters were compared between 56 chronic and 54 episodic migraine patients, and 50 healthy controls. Cortical curvature alterations were associated with abnormalities in the streamline count in episodic migraine patients compared to controls, with higher curvature values in the frontal and temporal poles being related to a higher streamline count. Lower streamline count was found in migraine compared to controls in connections between cortical regions within each of the four lobes. Higher streamline count was found in migraine in connections between subcortical regions, the insula, and the cingulate and orbitofrontal cortex, and between the insula and the temporal region. The connections between the caudate nucleus and the orbitofrontal cortex presented worse connectivity in chronic compared to episodic migraine. The hippocampus was involved in connections with higher and lower number of streamlines in chronic migraine. Strengthening of structural networks involving pain processing and subcortical regions coexists in migraine with weakening of cortical networks within each lobe. The multimodal analysis offers a new insight about the association between brain structure and connectivity., Planchuelo‐Gómez et al. associate structural connectivity with gray matter morphometry. In chronic and episodic migraine, strengthened connectivity with pain processing regions, and higher cortical curvature related to weakened connectivity within each lobe were found. These results give a new insight about migraine neuroimaging biomarkers.

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 The COVID-19 pandemic outbreak has dramatically disrupted healthcare systems. Two rapid WHO pulse surveys studied disruptions in mental health services, but did not particularly focus on neurology. Here, a global survey was conducted and addresses the impact of the pandemic on neurology services. Methods A cross-sectional study was carried out in which 34 international neurological associations were asked to distribute the survey to national associations. The responses represented the national situation, in November–December 2020, with regard to the main disrupted neurological services, reasons and the mitigation strategies implemented as well as the disruption on training of residents and on neurological research. A comparison with the situation in February–April 2020, first pandemic wave, was also requested. Findings 54 completed surveys came from 43 countries covering all the 6 WHO regions. Overall, neurological services disruption was reported as mild by 26%, moderate by 30%, complete by 13% of associations. The most affected services were cross-sectoral neurological services (57%) and neurorehabilitation (56%). The second wave of the pandemic, however, was associated with the improvement of service provision for diagnostics services (44%) and for neurorehabilitation (41%). Governmental directives were the major cause of services’ disruption (56%). Mitigation strategies were mostly established through telemedicine (48%). Almost half of respondents reported a significant impact on neurological research (48%) and educational activities (60%). Most associations (67%) were not involved in decision making for neurological patients’ issues by their national government. Interpretation The COVID-19 pandemic affects neurological services and raises the universal need for the development of neurological health care at the policy, systems and services levels. A global national plan on mitigation strategies for disruption of neurological services during pandemic situations should be established and neurological scientific and patients associations should get involved in decision making. Supplementary Information The online version contains supplementary material available at 10.1007/s00415-021-10641-3.

Background: Series of patients with SARS‐CoV‐2 infection report headache in 6%‐15% of cases, although some data suggest that the actual frequency is higher, and that headache is not associated with fever. No study published to date has analyzed the characteristics of headache in these patients. Objective: To analyze the characteristics of COVID‐19 related headaches. Methods: We conducted a survey of Spaniard healthcare professionals who have been infected by SARS‐CoV‐2 and presented headache during the course of the disease. The survey addressed respondents’ medical history and headache characteristics, and we analyzed the association between both. Results: We analyzed the responses of a sample of 112 healthcare professionals. History of migraine was reported by 20/112 (17.9%) of respondents, history of tension‐type headache by 8/112 (7.1%), and history of cluster headache was reported by a single respondent; 82/112(73.2%) of respondents had no history of headache. Headache presented independently of fever, around the third day after symptom onset. The previous history of migraine was associated with a higher frequency of pulsating headache (20% in patients with previous migraine vs 4.3% in those with no history of migraine, P = .013). Conclusion: Headache is often holocranial, hemicranial, or occipital, pressing, and worsens with physical activity or head movements. Because the characteristics of the headache and the associated symptoms are heterogeneous in our survey, we suggest that several patterns with specific pathophysiological mechanisms may underlie the headache associated with COVID‐19.

Introduction: When a patient is diagnosed with primary headache or craniofacial neuralgia in the emergency department or in primary care, and is referred to a neurologist due to the complexity of the case, it is useful to know whether additional examination should be sought and the priority (urgent, preferential, or normal) with which the patient should be seen. This will avoid unnecessary delays in patients with disabling headache and where organic causes are suspected.In order to issue recommendations on this matter, the Spanish Society of Neurology's Headache Study Group has decided to create a series of agreed recommendations constituting a referral protocol for patients with headache and/or craniofacial neuralgia. Development: Young neurologists with an interest and experience in headache were invited to draft a series of practical guidelines in collaboration with the Spanish Society of Neurology's Headache Study Group Executive Committee. For practical reasons, the document was divided into 2 articles: this first article focuses on primary headaches and craniofacial neuralgias and the second on secondary headaches. In order for the recommendations to be helpful for daily practice they follow a practical approach, with tables summarising referral criteria, examinations to be performed, and referral to other specialists. Conclusions: We hope to offer a guide and tools to improve decision-making regarding patients with headache, identifying complementary tests to prioritise and referral pathways to be followed, in order to avoid duplicated consultations and delayed diagnosis and treatment. Resumen: Introducción: Cuando tras una correcta anamnesis y exploración neurológica se diagnostica a un paciente con una cefalea primaria o una neuralgia craneofacial en urgencias o atención primaria y se decide derivar a neurología por complejidad es útil conocer si además se deberían solicitar exploraciones complementarias y la preferencia (urgente, preferente o normal) con la que se debería derivar para que el paciente llegue a la consulta del neurólogo sin demoras innecesarias en pacientes con dolores incapacitantes o con sospecha de organicidad.Por este motivo, el Grupo de Estudio de Cefalea de la Sociedad Española de Neurología, ha decidido crear unas recomendaciones consensuadas que establezcan un protocolo de derivación de pacientes con cefalea y/o neuralgias craneofaciales. Desarrollo: Se ha contactado con neurólogos jóvenes con interés y experiencia en cefalea y con la Junta Directiva del Grupo de Estudio de Cefalea de la Sociedad Española de Neurología que han desarrollado este documento que, por razones prácticas, se ha dividido en 2 artículos. Esta primera centrada en las cefaleas o neuralgias craneofaciales primarias y una segunda que se focaliza en las cefaleas secundarias. El enfoque es práctico con tablas que resumen los criterios de derivación con exploraciones complementarias y otros especialistas a los que derivar, para que sea útil y facilite su uso en nuestra práctica asistencial diaria. Conclusiones: Esperamos ofrecer una guía y herramientas para mejorar la toma de decisiones ante un paciente con cefalea, valorando exploraciones a priorizar y qué circuitos seguir para así evitar la duplicación de consultas y retrasos en el diagnóstico y en el tratamiento.

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 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.

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 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: Headache is identified as a common post-COVID sequela experienced by COVID-19 survivors. The aim of this pooled analysis was to synthesize the prevalence of post-COVID headache in hospitalized and non-hospitalized patients recovering from SARS-CoV-2 infection. Methods: MEDLINE, CINAHL, PubMed, EMBASE, and Web of Science databases, as well as medRxiv and bioRxiv preprint servers, were searched up to 31 May 2021. Studies or preprints providing data on post-COVID headache were included. The methodological quality of the studies was assessed using the Newcastle-Ottawa Scale. Random effects models were used for meta-analytical pooled prevalence of post-COVID headache. Data synthesis was categorized at hospital admission/symptoms' onset, and at 30, 60, 90, and ≥180 days afterwards. Results: From 9573 studies identified, 28 peer-reviewed studies and 7 preprints were included. The sample was 28,438 COVID-19 survivors (12,307 females; mean age: 46.6, SD: 17.45 years). The methodological quality was high in 45% of the studies. The overall prevalence of post-COVID headache was 47.1% (95% CI 35.8–58.6) at onset or hospital admission, 10.2% (95% CI 5.4–18.5) at 30 days, 16.5% (95% CI 5.6–39.7) at 60 days, 10.6% (95% CI 4.7–22.3) at 90 days, and 8.4% (95% CI 4.6–14.8) at ≥180 days after onset/hospital discharge. Headache as a symptom at the acute phase was more prevalent in non-hospitalized (57.97%) than in hospitalized (31.11%) patients. Time trend analysis showed a decreased prevalence from the acute symptoms’ onset to all post-COVID follow-up periods which was maintained afterwards. Conclusion: This meta-analysis found that the prevalence of post-COVID headache ranged from 8% to 15% during the first 6 months after SARS-CoV-2 infection.

Objective To investigate the association of headache during the acute phase of SARS-CoV-2 infection with long-term post-COVID headache and other post-COVID symptoms in hospitalised survivors. Methods A case-control study including patients hospitalised during the first wave of the pandemic in Spain was conducted. Patients reporting headache as a symptom during the acute phase and age- and sex-matched patients without headache during the acute phase participated. Hospitalisation and clinical data were collected from medical records. Patients were scheduled for a telephone interview 7 months after hospital discharge. Participants were asked about a list of post-COVID symptoms and were also invited to report any additional symptom they might have. Anxiety/depressive symptoms and sleep quality were assessed with the Hospital Anxiety and Depression Scale and the Pittsburgh Sleep Quality Index. Results Overall, 205 patients reporting headache and 410 patients without headache at hospitalisation were assessed 7.3 months (Standard Deviation 0.6) after hospital discharge. Patients with headache at onset presented a higher number of post-COVID symptoms (Incident Rate Ratio: 1.16, 95% CI: 1.03–1.30). Headache at onset was associated with a previous history of migraine (Odd Ratio: 2.90, 95% Confidence Interval: 1.41–5.98) and with the development of persistent tension-type like headache as a new post-COVID symptom (Odd Ratio: 2.65, 95% CI: 1.66–4.24). Fatigue as a long-term symptom was also more prevalent in patients with headache at onset (Odd Ratio: 1.55, 95% CI: 1.07–2.24). No between-group differences in the prevalence of anxiety/depressive symptoms or sleep quality were seen. Conclusion Headache in the acute phase of SARS-CoV-2 infection was associated with higher prevalence of headache and fatigue as long-term post-COVID symptoms. Monitoring headache during the acute phase could help to identify patients at risk of developing long-term post-COVID symptoms, including post-COVID headache.

Background Headache is a frequent symptom following COVID-19 immunization with a typical onset within days post-vaccination. Cases of cerebral venous thrombosis (CVT) have been reported in adenovirus vector-based COVID-19 vaccine recipients. Findings We reviewed all vaccine related CVT published cases by April 30, 2021. We assessed demographic, clinical variables and the interval between the vaccination and onset of headache. We assessed whether the presence of headache was associated with higher probability of death or intracranial hemorrhage. We identified 77 cases of CVT after COVID-19 vaccination. Patients’ age was below 60 years in 74/77 (95.8%) cases and 61/68 (89.7%) were women. Headache was described in 38/77 (49.4%) cases, and in 35/38 (92.1%) was associated with other symptoms. Multiple organ thrombosis was reported in 19/77 (24.7%) cases, intracranial hemorrhage in 33/77 (42.9%) cases and 19/77 (24.7%) patients died. The median time between vaccination and CVT-related headache onset was 8 (interquartile range 7.0–9.7) days. The presence of headache was associated with a higher odd of intracranial hemorrhage (OR 7.4; 95% CI: 2.7–20.8, p p = 0.213). Conclusion Delayed onset of headache following an adenovirus vector-based COVID-19 vaccine is associated with development of CVT. Patients with new-onset headache, 1 week after vaccination with an adenovirus vector-based vaccine, should receive a thorough clinical evaluation and CVT must be ruled out.

ObjectiveTo explore the experiences of patients suffering from new daily persistent headache (NDPH) regarding the diagnostic process, treatment and medical care.DesignA qualitative phenomenological study was conducted.SettingA specialised headache unit at two university hospitals in Spain between February 2017 and December 2018.ParticipantsPatients diagnosed with NDPH according to the International Classification of Headache disorders (third beta edition).MethodsPurposeful sampling was performed. Data were collected using unstructured and semistructured interviews, researchers’ field notes and patients’ drawings. An inductive thematic analysis was used to identify significant emerging themes from interviews, field notes and descriptions of patients’ drawings. Also, Guillemin’s proposal was used to analyse the contents of drawings.ResultsNineteen patients with a mean age of 45.3 were recruited. Four main themes emerged: (1) Seeking a diagnosis, patients visit many doctors without receiving a clear answer and their diagnosis is delayed; (2) Self-medication—minimising pill intake, medication is ineffective, and therefore, some patients discontinue treatment, or are flexible with how they take medication; (3) Trying other non-pharmacological options, many patients turn to other therapies and complementary and/or alternative therapies as a second option, however these are ineffective and (4) Medical care, with two subthemes, referrals and lacking continuity of care, and building the doctor–patient relationship. Patients describe how the referral breaks the continuity of care, and how they identify the traits of a doctor who is approachable and which behaviours the doctor should avoid when caring for patients.ConclusionsAn in-depth knowledge of the beliefs and expectations of patients with NDPH will allow the professional to establish a relationship of trust, which will improve the patients’ knowledge of which therapies are the most appropriate, and to establish expectations based on the relationship with the doctor, and not only on patients’ beliefs.

Acute and post-acute neurological symptoms, signs and diagnoses have been documented in an increasing number of patients infected by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which causes Coronavirus Disease 2019 (COVID-19). In this review, we aimed to summarize the current literature addressing neurological events following SARS-CoV-2 infection, discuss limitations in the existing literature and suggest future directions that would strengthen our understanding of the neurological sequelae of COVID-19. The presence of neurological manifestations (symptoms, signs or diagnoses) both at the onset or during SARS-CoV-2 infection is associated with a more severe disease, as demonstrated by a longer hospital stay, higher in-hospital death rate or the continued presence of sequelae at discharge. Although biological mechanisms have been postulated for these findings, evidence-based data are still lacking to clearly define the incidence, range of characteristics and outcomes of these manifestations, particularly in non-hospitalized patients. In addition, data from low- and middle-income countries are scarce, leading to uncertainties in the measure of neurological findings of COVID-19, with reference to geography, ethnicity, socio-cultural settings, and health care arrangements. As a consequence, at present a specific phenotype that would specify a post-COVID (or long-COVID) neurological syndrome has not yet been identified. Supplementary Information The online version contains supplementary material available at 10.1007/s00415-021-10848-4.

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.

ObjectiveTo investigate the association of pre-existing migraine in patients hospitalised and who recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with the presence of post-coronavirus disease (COVID) symptoms.BackgroundNo study has investigated the role of migraine as a risk factor for development of post-COVID symptoms.MethodsA case-control study including individuals hospitalised during the first wave of the pandemic (from February 20 to May 31, 2020) was conducted. Patients with confirmed previous diagnosis of migraine were considered cases. Two age- and sex-matched individuals without a history of headache per case were also recruited as controls. Hospitalisation/clinical data were collected from hospital medical records. Patients were scheduled for a telephone interview. A list of post-COVID symptoms was systematically evaluated, but participants were invited to freely report any symptom. The Hospital Anxiety and Depression Scale and the Pittsburgh Sleep Quality Index were used to assess anxiety/depressive symptoms and sleep quality. Multivariable conditional logistic regression models were constructed.ResultsOverall, 57 patients with confirmed diagnosis of migraine and 144 non-migraine controls who had recovered from COVID-19 were assessed at 7.3 months (SD 0.6) after hospital discharge. The number of post-COVID symptoms in the migraine group was significantly greater (OR 1.70, 95% CI 1.29–2.25, P < 0.001) than in the non-migraine group. Fatigue was significantly more prevalent (OR 2.89, 95% CI 1.32–6.32, P = 0.008) in the migraine group. However, no between-groups difference in the prevalence of headache as a post-COVID symptom was detected.ConclusionPatients with a history of migraine who recovered from COVID-19 exhibited more long-term fatigue as post-COVID sequelae than those without migraine. Some of the pathophysiological changes associated with migraine could predispose to the occurrence of post-COVID symptoms.

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.

La cefalea es un síntoma frecuente en urgencias. Evaluamos la frecuencia y tipo de datos de alarma en pacientes que acudieron a urgencias y tuvieron un diagnóstico confirmado de trombosis de senos venosos cerebrales (TSVC) o enfermedad por coronavirus 2019 (Covid-19). También analizamos pacientes que fueron dados de alta de urgencias con un diagnóstico definitivo de cefalea tipo tensión (CTT). Todos los pacientes con TSVC o Covid-19 que acudieron a urgencias con cefalea tenía al menos un dato de alarma. La TSVC debe considerarse en el diagnóstico diferencial de los pacientes con cefalea y datos de alarma. En pacientes con cefalea de nueva aparición con datos de alarma durante 2020-2021, la presencia de una posible infección por Covid-19 debe ser considerada. La CTT está sobrediagnosticada en urgencias, los pacientes con un diagnóstico de CTT presentaron datos de alarma en un 80% de los casos, haciendo el diagnóstico de CTT incompatible., Departamento de Medicina, Dermatología y Toxicología, Doctorado en Investigación en Ciencias de la Salud

Introducción: Se han reportado casos de trombosis venosas cerebrales en personas vacunadas frente a COVID-19 con vacunas vectoriazadas con adenovirus no replicantes. Aportamos recomendaciones sobre el diagnóstico y manejo de pacientes con esta complicación. Método: El Grupo de Trabajo multidisciplinar, liderado por la Federación de Asociaciones Científico Médicas Españoles (FACME) y representado por distintas sociedades científicas, revisó la evidencia disponible publicada en la literatura y en los informes de la Agencia Europea del Medicamento. Se estableció una definición de caso sospechoso y recomendaciones diagnóstico-terapéuticas de la trombocitopenia trombótica inducida por la vacunación. Resultados: Se considera caso sospechoso aquella trombosis venosa cerebrales ocurridas entre 3 y 21 días tras la administración de vacunas no replicantes de adenovirus que presenten un valor de plaquetas inferior a 150.000 plaquetas por μL o un descenso del 50% respecto de la cifra previa. Los datos sugestivos de trombocitopenia trombótica inducida por la vacunación incluyen la presencia de anticuerpos anti-factor plaquetario tipo 4, la elevación de dímero-D cuatro veces por encima del límite superior de la normalidad o la ausencia de justificación de la trombosis. En su tratamiento, se recomienda administrar inmunoglobulina humana inespecífica intravenosa o realizar plasmaféresis en su defecto, evitar el uso de heparina, empleando como anticoagulantes argatroban, bivalirudina, fondaparinux, rivaroxaban o apixaban, y evitar la transfusión de plaquetas. Conclusiones: Las vacunas de vectores no replicantes de adenovirus pueden asociarse a trombosis venosas cerebrales con trombocitopenia, en cuyo manejo es importante el tratamiento del fenómeno disinmune y de la trombosis venosa cerebral.

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 &lt, 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 &lt, 0.001). This association was maintained in the multivariate regression analysis (OR: 0.540, 95% CI: 0.333–0.746, p &lt, 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 We propose a new outcome measure to assess the efficacy of migraine treatments translating the approach of the Global Burden of Disease studies from a societal to an individual level: Instead of calculating “years lived with disability”, we suggest estimating “time lost due to an attack”. Methods Time lost due to an attack is calculated by multiplying the duration and the degree of impaired functioning during an attack. Results Time lost due to an attack, different from other outcome measures, does not just focus on the short-term analgesic effects of treatments, but rather on the improvement of all migraine symptoms and restoration of functioning, also considering therapy-related impairment. Importantly, time lost due to an attack measures the entire time patients are not functioning normally, from onset to complete resolution. Conclusions Time lost due to an attack represents a new paradigm to assess migraine burden in single patients for a patient-centered evaluation of both acute and prophylactic treatments.

Background Epicrania fugax is included in the appendix of the International Classification of Headache Disorders and is characterized as recurrent brief attacks of linear or zigzag pain moving across the cranial surface, commencing and terminating in the distribution of different nerves. We present a new case of epicrania fugax in which the headache was the presenting symptom of a cerebellar abscess. Case report We present a 58-year-old woman with prior history of Chiari I malformation who underwent suboccipital craniectomy. Two weeks after surgery, she experienced paroxysmal pain episodes of 1–3 seconds, with constant linear trajectory from the right occipital surface to the right orbital region, remaining pain free between episodes. Cranial tomography showed a hypodense intraaxial lesion in the right cerebellar hemisphere. Magnetic Resonance Imaging exhibited intralesional bleeding and peripheral enhancement after gadolinium administration. Post-surgical cerebellar abscess was diagnosed and antibiotic therapy was started; the patient underwent urgent surgical drainage. Pain disappeared after the surgery and the patient remains pain free with 12 months of follow-up. Conclusion Posterior fossa abnormalities have been described as a possible cause of secondary epicrania fugax. The presence of red flags should encourage conducting of paraclinical tests to rule out a symptomatic form.

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.

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 ...

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.

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.

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.

Background and purpose The COVID-19 (SARS-CoV-2) outbreak has disrupted residency programmes due to university and hospitals' priorities to face this emergency at all cost. Most research projects and clinical trials were temporarily stopped or postponed. The Resident and Research Fellow Section (RRFS) of the European Academy of Neurology (EAN) has decided to assess the impact of the COVID-19 pandemic on neurology training. Methods All EAN RRFS members were invited to fill out an online questionnaire of 40 items concerning their clinical involvement during the COVID-19 emergency, and the impact of the pandemic on their training (Appendix S1). Results Of the 227 RRFS members who completed the questionnaire, 222 were from Europe, and of those 111 were from Portugal, Italy or France. Responders highlighted that severe restrictions have been imposed to face this pandemic, including reduction of inpatient beds, prohibition of in-person visits and limitation to hospital access for patients' relatives. This was accompanied by an increase in email correspondence and phone calls with 50% of countries allowing telemedicine to reach outpatients. Seventy-nine per cent of the respondents felt that the pandemic will probably have a serious impact on their training and career. Conclusion The pandemic led to a disruption of neurology activities, including medical training and research. The long-run impact of these changes remains unknown, but it will probably change the way neurology practice and training will be organized for future generations.

Encephalopathy is a common complication of COVID-19 that can both be a challenge to manage and also negatively impacts prognosis. Whilst encephalopathy may be due to common systemic causes, such as hypoxia, COVID-19 has also been associated with more prolonged encephalopathy due to less common but nevertheless severe complications, such as inflammation of the brain parenchyma, cerebrovascular involvement and seizures, which may be disproportionate to COVID-19 severity and which require specific management. The aim of this review is to provide pragmatic guidance on the management of COVID-19 encephalopathy through a consensus agreement of the Global COVID-19 Neuro-Research Coalition. A systematic literature search of Medline, MedRxiv, and BioRx was conducted between 1st January 2020 and 11th June 2021 with additional review of references cited within the identified bibliographies. A modified Delphi-approach was then undertaken to develop recommendations along with a parallel approach to score the strength of both the recommendation and the supporting evidence. This manuscript presents analysis of contemporaneous evidence for definition, epidemiology, and pathophysiology of COVID-19 encephalopathy and practical guidance for clinical assessment, investigation, and acute and long-term management.

Resumen: Objetivos: Desde el inicio de la pandemia por el virus SARS-CoV2 la Sociedad Española de Neurología (SEN) creó un registro de afectación neurológica para informar al neurólogo clínico. Las encefalopatías y encefalitis fueron una de las complicaciones más descritas. Analizamos las características de las mismas. Pacientes y métodos: Estudio descriptivo retrospectivo, observacional multicéntrico, de pacientes con sintomatología compatible con encefalitis o encefalopatía, introducidos en el Registro SEN COVID-19 desde el 17 de marzo hasta el 6 de junio de 2020. Resultados: Se han registrado 232 casos con síntomas neurológicos, 51 casos de encefalopatía/encefalitis (21,9%). Ningún paciente era trabajador sanitario. Los síndromes más frecuentes fueron: cuadro confusional leve-moderado (33%) y encefalopatía grave o coma (9,8%). El tiempo medio entre el inicio de la infección y la clínica neurológica fue de 8,02 días. Punción lumbar en el 60,8% de pacientes; solo hubo un caso con PCR positiva. Resonancia craneal en el 47% de los pacientes (alterada en el 7,8% de ellos). Se realizó electroencefalograma en el 41,3% de los casos (alterado en el 61,9% de los mismos). Conclusiones: Las encefalopatías y encefalitis son dos de las complicaciones más frecuentes descritas en el SEN COVID-19. Más de un tercio de los pacientes presentó un cuadro de síndrome confusional leve o moderado. El tiempo medio de aparición de la sintomatología neurológica desde el inicio de la infección fue de 8 días (hasta 24 h antes en mujeres que en hombres). El electroencefalograma fue la prueba más sensible en estos pacientes, encontrando muy pocos casos con alteraciones en las pruebas de neuroimagen. Todos los pacientes que recibieron tratamiento con bolos de corticoides o inmunoglobulinas tuvieron una evolución favorable. Abstract: Objectives: Since the beginning of the COVID-19 pandemic, the Spanish Society of Neurology has run a registry of patients with neurological involvement for the purpose of informing clinical neurologists. Encephalopathy and encephalitis were among the most frequently reported complications. In this study, we analyse the characteristics of these complications. Patients and methods: We conducted a retrospective, descriptive, observational, multicentre study of patients with symptoms compatible with encephalitis or encephalopathy, entered in the Spanish Society of Neurology's COVID-19 Registry from 17 March to 6 June 2020. Results: A total of 232 patients with neurological symptoms were registered, including 51 cases of encephalopathy or encephalitis (21.9%). None of these patients were healthcare professionals. The most frequent syndromes were mild or moderate confusion (33%) and severe encephalopathy or coma (9.8%). The mean time between onset of infection and onset of neurological symptoms was 8.02 days. Lumbar puncture was performed in 60.8% of patients, with positive PCR results for SARS-CoV-2 in only one case. Brain MRI studies were performed in 47% of patients, with alterations detected in 7.8% of these. EEG studies were performed in 41.3% of cases, detecting alterations in 61.9%. Conclusions: Encephalopathy and encephalitis are among the complications most frequently reported in the registry. More than one-third of patients presented mild or moderate confusional syndrome. The mean time from onset of infection to onset of neurological symptoms was 8 days (up to 24 hours earlier in women than in men). EEG was the most sensitive test in these patients, with very few cases presenting alterations in neuroimaging studies. All patients treated with boluses of corticosteroids or immunoglobulins progressed favourably.

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 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.

We investigated if dynamic pressure pain sensitivity in the symptomatic area is associated with pressure sensitivity in local and distant pain-free areas in cluster headache (CH). A pressure algometry set consisting of 8 rollers with fixed pressure levels ranging from 500 to 5300 g was used to assess dynamic pressure pain sensitivity in men with episodic CH. Each roller was moved from an anterior-to-posterior direction over the temporalis muscle. The load level of the first painful roller was considered the dynamic pain threshold (DPT). Further, pain elicited during DPT (roller evoked pain) was also assessed. We used a pressure algometer to determine pressure pain thresholds (PPTs) over the temporalis muscle, C5/C6 joint, second metacarpal, and tibialis anterior. Patients were assessed in an asymptomatic (remission) phase, at least 6 months after their last cluster period and without taking pharmacological treatment. Forty men with episodic CH (mean age 42 years) were included. Both outcomes, DPTs (r = 0.781, P

We appreciate Dr. Goadsby's comment on our article.1 As we used an online questionnaire, we were not able to catch the differentiation between regular stabs, which could be—as Dr. Goadsby pointed out—interpreted as throbbing. In our questionnaire, patients were allowed to describe more than 1 pain quality, and within the 219 (19.8%) participants who described stabbing headache, 58 (26.5%) of them described throbbing pain as well. The frequency of typical migraine symptoms was even higher than in the group of patients with stabbing pain when compared with those with throbbing pain: unilateral pain (24.4% vs 12.2%), photophobia (48.3% vs 37.7%), phonophobia (66.3% vs 59.4%), osmophobia (29.1% vs 25.9%), nausea (54.1% vs 51.9%), or vomiting (30.8% vs 31%). Therefore, future studies should clarify the cadence of the stabs. In addition, we calculated the percentage of patients with at least 1 migrainous symptom in the entire sample, including throbbing or stabbing pain, photophobia, phonophobia, osmophobia, vomiting, cranial autonomic symptoms, or aggravation with movement, and we found that it was 91%. Both findings suggest that migraine features are common in patients with delayed alcohol-induced headache despite just a proportion of them fulfilling International Classification of Headache Disorders phenotypic criteria.

[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.

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

OBJECTIVE The aim of this study was to collect and rate Green Flags, that is, symptoms or pieces of information indicating that a patient is more likely to suffer from a primary than from a secondary headache. BACKGROUND When assessing headaches, a central question to be answered is whether the pain is primary or secondary to another disorder. To maximize the likelihood of a correct diagnosis, relevant signs and symptoms must be sought, identified, and weighed against each other. METHODS The project was designed as a Delphi study. In the first round, an expert panel proposed green flags that were rated anonymously in two subsequent rounds. Proposals with an average rating of 4.0 and higher on a scale from 0 to 5 reached consensus. RESULTS Five Green Flags reached consensus: (i) "The current headache has already been present during childhood"; (ii) "The headache occurs in temporal relationship with the menstrual cycle"; (iii) "The patient has headache-free days"; (iv) "Close family members have the same headache phenotype"; and (v) "Headache occurred or stopped more than one week ago." CONCLUSIONS We propose five Green Flags for primary headache disorders. None being a pathognomonic sign, we recommend searching for both Green Flags and Red Flags. If both are present, a secondary headache should be suspected. Overall, the application of the Green Flag concept in clinical practice is likely to increase diagnostic accuracy and improve diagnostic resource allocation. Prospective studies in clinical populations should be conducted to validate these Green Flags.

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.