Global uncertainty in the diagnosis of neurological complications of SARS-CoV-2 infection by both neurologists and non-neurologists: An international inter-observer variability study.

INTRODUCTION: Uniform case definitions are required to ensure harmonised reporting of neurological syndromes associated with SARS-CoV-2. Moreover, it is unclear how clinicians perceive the relative importance of SARS-CoV-2 in neurological syndromes, which risks under- or over-reporting. METHODS: We invited clinicians through global networks, including the World Federation of Neurology, to assess ten anonymised vignettes of SARS-CoV-2 neurological syndromes. Using standardised case definitions, clinicians assigned a diagnosis and ranked association with SARS-CoV-2. We compared diagnostic accuracy and assigned association ranks between different settings and specialties and calculated inter-rater agreement for case definitions as "poor" (κ ≤ 0.4), "moderate" or "good" (κ > 0.6). RESULTS: 1265 diagnoses were assigned by 146 participants from 45 countries on six continents. The highest correct proportion were cerebral venous sinus thrombosis (CVST, 95.8%), Guillain-Barré syndrome (GBS, 92.4%) and headache (91.6%) and the lowest encephalitis (72.8%), psychosis (53.8%) and encephalopathy (43.2%). Diagnostic accuracy was similar between neurologists and non-neurologists (median score 8 vs. 7/10, p = 0.1). Good inter-rater agreement was observed for five diagnoses: cranial neuropathy, headache, myelitis, CVST, and GBS and poor agreement for encephalopathy. In 13% of vignettes, clinicians incorrectly assigned lowest association ranks, regardless of setting and specialty. CONCLUSION: The case definitions can help with reporting of neurological complications of SARS-CoV-2, also in settings with few neurologists. However, encephalopathy, encephalitis, and psychosis were often misdiagnosed, and clinicians underestimated the association with SARS-CoV-2. Future work should refine the case definitions and provide training if global reporting of neurological syndromes associated with SARS-CoV-2 is to be robust.

Impact of the COVID-19 pandemic on the training of Spanish neurology residents

Introduction: The COVID-19 pandemic has transformed medical practice and severely disrupted the training of medical residents worldwide. The Spanish Society of Neurology conducted a study to assess its impact on the training of neurology residents in Spain. Method(s): We performed a descriptive, cross-sectional study through a survey distributed by e-mail to all neurology residents belonging to the Society. The survey included questions on demographic variables, care activity, and personal and educational impact of the pandemic, as well as respondents' expectations for the future of their work in the post-pandemic era. Result(s): Of 422 surveys sent, we received a total of 152 responses (36%);79 respondents (52%) were women and 73 (48%) were men. By year of residency, 51 respondents (33.6%) were in the fourth year, 45 (29.6%) in the third year, 28 (18.4%) in the second year, and 28 (18.4%) in the first year. A total of 139 respondents (90.8%) reported changes in hospital activity, and 126 (82.8%) considered the situation to have had a negative impact on their training, with 99 (64.7%) having lost non-recoverable rotations. Sixty-six percent of respondents (n=101) expressed a desire to extend their residency period. Conclusion(s): The pandemic has had an extremely severe impact on all areas of the health system, with trainee physicians being one of the most affected groups. Among neurology residents, the crisis has caused significant shortcomings in their training and clinical activities, through the suspension of specific rotations. A high percentage of respondents wished to extend the residency period.Copyright © 2021 Sociedad Espanola de Neurologia

Characterization and Analysis of Neurologic Adverse Events Associated with COVID-19 Vaccination

Objective: To characterize the incidence and spectrum of neurological adverse events (AE) after COVID-19 vaccination. Background: The devastating COVID-19 pandemic has led to 230 million people diagnosed and greater than 4.8 million deaths worldwide. Widespread vaccination efforts have resulted in administration of over 6 million vaccine doses to curb the significant health and socioeconomic impacts of the disease. While there are numerous reports of adverse events following COVID-19 vaccine, there is limited characterization of the spectrum of neurological AEs post-vaccination. Design/Methods: Data was gathered from the publicly available Vaccine Adverse Event Reporting System (VAERS), a passive reporting system not implying causality. Among individuals who received the J&J, Moderna, and Pfizer vaccines from 1/1/2021-6/14/2021, 314,610 adverse events were reported and these were reviewed by Neurology trained clinicians to determine the presence of various neurological AEs (40 conditions coded). Results: 306,473,169 COVID vaccine dose were administered in the USA during the study period with 314,610 total AEs (0.10%) and 105,930 neurological AEs (0.03%) reported. J&J vaccine was associated with the most AEs (17,670, 0.15%), followed by Moderna (42656, 0.03%) and Pfizer (42267, 0.03%). On average more events were reported in women (71%) and a majority occurred after the first dose (54%). < 1 events were reported per million vaccine doses for serious neurological conditions such as Bell's palsy (0.0007%), Guillain-Barre syndrome (0.00009%), cerebral venous thrombosis (0.00005%), transverse myelitis (0.00003%), and acute disseminated encephalomyelitis (0.00006%). Overall neurological complications following vaccine were drastically lower than complications post-COVID infection (14-80%). Conclusions: Adverse neurological events following COVID-19 vaccination are extremely rare and significantly less common than adverse neurological effects following SARS-CoV-2 infection. Current evidence suggests that along with being up to 100,000 times more likely to experience a major complication from COVID infection vs. vaccine, the risk of neurological complication is up to 5000 times more likely from infection itself.

[Effect of treatment with benzodiazepines on the hospital prognosis of Coronavirus disease 2019]. / Efecto del tratamiento con benzodiacepinas en el pronóstico hospitalario de la enfermedad por coronavirus 2019.

INTRODUCTION: The consequences of the use of of benzodiazepines in coronavirus disease 2019 have not yet been studied. We compared the hospital prognosis of patients hospitalized for coronavirus disease 2019 in benzodiazepine users and non-users. PATIENTS AND METHODS: Observational study with a retrospective cohort design. All consecutive patients admitted with a confirmed diagnosis of coronavirus disease 2019 were included. The patients under chronic treatment with benzodiazepines at the time of admission were studied and compared with non-users. The primary objective was to analyze the mortality of patients who used chronic benzodiazepines at the time of admission and compare them with those who did not use them. The secondary objective was to analyze the risk of severe disease due to coronavirus 2019, acute respiratory distress syndrome and admission to the Intensive Care Unit in both groups of patients. RESULTS: We included 576 patients, 138 (24.0%) used benzodiazepines. After adjusting for sex, age, baseline situation and all the different variables between both groups, benzodiazepine users did not show a higher odds of mortality (OR: 1,1, IC 95%: 0,7-1,9, p = 0,682) or higher risk of severe disease due to coronavirus 2019 (OR: 1.2, 95% CI: 0.7-1.8, p = 0.523). They also did not have a higher risk of acute respiratory distress syndrome (OR: 1.2, IC 95%: 0.8-1.9, p = 0.315) or more admission to the Intensive Care Unit (OR: 0.8, 95% CI: 0.4-1.4, p = 0.433). CONCLUSION: In our sample, treatment with benzodiazepines at the time of admission was not associated with a worse hospital prognosis in patients with coronavirus disease 2019.

TITLE: Efecto del tratamiento con benzodiacepinas en el pronóstico hospitalario de la enfermedad por coronavirus 2019.Introducción. Las consecuencias del consumo de benzodiacepinas en el marco de la la enfermedad por coronavirus 2019 (COVID-19) no se habían estudiado hasta ahora. En el presente estudio se comparó el pronóstico hospitalario de pacientes ingresados por COVID-19 que tomaban benzodiacepinas con el de otros ingresados por idéntico motivo que no las tomaban. Pacientes y métodos. Estudio observacional de cohortes retrospectivo. En el estudio se admitió a todos los pacientes consecutivos ingresados con un diagnóstico confirmado de COVID-19. Se estudió a los pacientes que en el momento del ingreso estaban en tratamiento crónico con benzodiacepinas en comparación con otros que no las tomaban. El objetivo principal fue analizar la mortalidad de dichos pacientes con uso crónico de benzodiacepinas y compararla con la mortalidad de los que no tomaban. El objetivo secundario fue analizar en ambos grupos de pacientes el riesgo de padecer un cuadro grave por COVID-19, el síndrome de dificultad respiratoria aguda o el ingreso en la unidad de cuidados intensivos. Resultados. Se admitieron 576 pacientes, 138 (24,0%) de los cuales tomaban benzodiacepinas. Después del ajuste por sexo, edad, situación inicial y todas las variables diferentes entre ambos grupos, los pacientes que tomaban benzodiacepinas no mostraron una probabilidad mayor de muerte (odds ratio: 1,1; IC 95%: 0,7-1,9; p = 0,682) ni un riesgo más acusado de COVID-19 grave (odds ratio: 1,2; IC 95%: 0,7-1,8; p = 0,523). Tampoco presentaron un riesgo mayor de síndrome de dificultad respiratoria aguda (odds ratio: 1,2; IC 95%: 0,8-1,9; p = 0,315) ni de ingreso en la unidad de cuidados intensivos (odds ratio: 0,8; IC 95%: 0,4-1,4; p = 0,433). Conclusión. En esta muestra de pacientes con COVID-2019, el tratamiento con benzodiacepinas en el momento del ingreso no apareció asociado con un empeoramiento del pronóstico hospitalario.

1st Post-European Headache Federation Meeting: a review of the latest developments presented at the 2020 European Headache Federation Congress. / I Reunión Post-European Headache Federation: revisión de las novedades presentadas en el Congreso de la European Headache Federation de 2020.

INTRODUCTION: After the European Headache Federation (EHF) Congress, renowned Spanish neurologists specialised in migraine presented the most significant latest developments in research in this field at the Post-EHF Meeting. DEVELOPMENT: The main data presented concerning the treatment of chronic and episodic migraine were addressed, with attention paid more specifically to those related to preventive treatments and real-life experience in the management of the disease. An important review was carried out of the new therapeutic targets and the possibilities they offer in terms of understanding the pathophysiology of migraine and its treatment. An update was also presented of the latest developments in the treatment of migraine with fremanezumab, a monoclonal antibody recently authorised by the European Medicines Agency. Participants were also given an update on the latest developments in basic research on the pathology, as well as an overview of the symptoms of migraine and COVID-19. Finally, the repercussions of migraine in terms of its burden on the care and economic resources of the health system were addressed, along with its impact on society. CONCLUSIONS: The meeting summarised the content presented at the 14th EHF Congress, which took place in late June/early July 2020.

TITLE: I Reunión Post-European Headache Federation: revisión de las novedades presentadas en el Congreso de la European Headache Federation de 2020.Introducción. Tras la celebración del congreso de la European Headache Federation (EHF), reconocidos neurólogos españoles expertos en el tratamiento de la migraña expusieron en la Reunión Post-EHF las principales novedades presentadas en el congreso y relacionadas con ese ámbito. Desarrollo. Se abordan los principales datos presentados relacionados con el tratamiento de la migraña crónica y episódica; concretamente, los relacionados con los tratamientos preventivos y la experiencia en vida real en el manejo de la enfermedad. Se hizo una importante revisión de las nuevas dianas terapéuticas y las posibilidades que ofrecen en cuanto al conocimiento de la fisiopatología de la migraña y su tratamiento. Asimismo, se hizo una actualización de las novedades presentadas en el tratamiento de la migraña con fremanezumab, anticuerpo monoclonal recientemente autorizado por la Agencia Europea de Medicamentos. Se hizo una actualización de las novedades en investigación básica en la patología, así como una relación de los síntomas de migraña y COVID-19. Finalmente, se abordaron las implicaciones de la migraña en la carga sanitaria asistencial y económica, y su impacto en la sociedad. Conclusiones. En la reunión se hizo un resumen del contenido presentado en el 14 Congreso de la EHF, que tuvo lugar a finales de junio y principios de julio de 2020.

Infections as triggers of other central nervous system autoimmune disorders

Infectious diseases are often included in the differential diagnosis of many neurological disorders and syndromes. Besides the central and peripheral nervous system manifestations of microbiological agents, such as Zika virus, varicella zoster virus, herpes virus, Malaria, Epstein-Barr virus, West Nile virus influenza virus or recently severe acute respiratory syndrome coronavirus 2. Postinfectious manifestations of these agents cover autoimmune syndromes, including opsoclonus-myoclonus, cerebellitis, myelitis, acute demyelinating encephalomyelitis, and Bickerstaff brainstem encephalitis, among others. The frontier between acute and postinfectious is not always evident. The key diagnostic features will be summarized, including disease-specific antibodies, as anti- GQ1b in Bickerstaff encephalitis;and which ancillary exams might disentangle the presence of an acute infection or the evidence of a passed infection, such as oligoclonal bands or immunoglobulin M/G in serum or cerebrospinal fluid analysis. To date, different treatments have been proposed, including steroids, intravenous immunoglobulins, plasmapheresis or other immunotherapies, however evidence is limited, and evidence is relatively weak for most therapeutic options.

Telemedicine in the management of patients with headache: current situation and recommendations of the Spanish Society of Neurology's Headache Study Group. / Aplicación de la telemedicina en la asistencia a pacientes con cefaleas: situación actual y recomendaciones del Grupo de Estudio de Cefaleas de la Sociedad Española de Neurología.

INTRODUCTION: The COVID-19 pandemic has caused an unexpected boost to telemedicine. We analyse the impact of the pandemic on telemedicine applied in Spanish headache consultations, review the literature, and issue recommendations for the implementation of telemedicine in consultations. METHOD: The study comprised 3 phases: 1) review of the MEDLINE database since 1958 (first reported experience with telemedicine); 2) Google Forms survey sent to all members of the Spanish Society of Neurology's Headache Study Group (GECSEN); and 3) online consensus of GECSEN experts to issue recommendations for the implementation of telemedicine in Spain. RESULTS: COVID-19 has increased waiting times for face-to-face consultations, increasing the use of all telemedicine modalities: landline telephone (from 75% before April 2020 to 97% after), mobile telephone (from 9% to 27%), e-mail (from 30% to 36%), and video consultation (from 3% to 21%). Neurologists are aware of the need to expand the availability of video consultations, which are clearly growing, and other e-health and m-health tools. CONCLUSIONS: The GECSEN recommends and encourages all neurologists who assist patients with headaches to implement telemedicine resources, with the optimal objective of offering video consultation to patients under 60-65 years of age and telephone calls to older patients, although each case must be considered on an individual basis. Prior approval and advice must be sought from legal and IT services and the centre's management. Most patients with stable headache and/or neuralgia are eligible for telemedicine follow-up, after a first consultation that must always be held in person.

Clinical characterization of headache attributed to COVID-19: A series of 457 cases

Introduction: Headache is one of the most frequent symptoms of coronavirus disease 2019 (Covid-19). Most of the published series and cases described hospitalized patients, which could bias the results because of a more severe Covid-19. Objectives: In the present study we aim to describe the clinical phenotype of headache attributed to Covid-19 (HAC-19) including the full spectrum of patients, including cases managed both in primary care and hospital care. Methods:We screened the presence of headache all consecutive patients with a confirmed diagnosis of Covid-19, since the first hospitalized patient (March 8th, 2020) until April 11th. Patients with headache and capability to describe the headache phenotype were invited to participate. Diagnosis was confirmed by polymerase chain reaction test in all patients. A physician conducted a structured interview including demographic and clinical variables. Local ethics review board approved the study (PI 20- 1738). Results: A total of 138/576 (26.0%) hospitalized patients and 408/1690 (24.1%) primary care patients described headache, being.8 included in the study 105 and 352 of them. Mean age was 52.1±15.6 years, being 329 (72.0%) female, and 151 (33.0%) had pneumonia. Prior history of headache was described by 223 (48%) of patients, being migraine in 83 (18.2%). Headache was the first Covid-19 symptom in 126 (27.6%) patients and the mean duration of headache was 12.8 (16.1) days. The most frequent concomitant symptoms were olfactory disorders in 268 (58.6%) cases, followed by asthenia 335 (73.3%), cough 296 (64.8%), fever 259 (56.7%), and myalgia 223 (48.8%). Headache was the most bothersome Covid- 19 symptom in 69 (15.1%) cases, being the mean intensity 6.9±1.7. Patients estimated that headache allowed them to do 49.1±32.6% of their planned activities because of it. The headache was holocranial in 335 (73.3%), with frontal topography in 244 (53.4%), followed by temporal (121 (26.5%) and periocular in 97 (21.2%). Quality of pain was oppressive in 323 (70.7%) and throbbing in 66 (14.1%). Patients described avoidance of routine physical activity in 288 (63.0%) cases, photophobia in 150 (32.8%) cases, phonophobia in 146 (31.9%), and nausea in 69 (15.1%). The most frequently used symptomatic medication was paracetamol in 379 (82.9%), followed by ibuprofen in 70 (15.3%) and metamizole in 48 (10.5%). Conclusion: Headache is a frequent symptom in Covid- 19 disease. The clinical phenotype combines features from both tension-type headache and migraine, with moderate intensity and significant disability. A quarter of patients described headache as the first Covid-19 symptom.

Encephalopathy and encephalitis during acute SARS-CoV-2 infection. Spanish Society of Neurology COVID-19 Registry. / Encefalopatías y encefalitis durante la infección aguda por SARS-CoV2. Registro de la Sociedad Española de Neurología SEN COVID-19.

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 24hours 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.