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

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

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

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.

Neurofilament light chain levels in pregnant multiple sclerosis patients: a prospective cohort study.

BACKGROUND AND PURPOSE: Neurofilament light chain is a cytoskeletal protein of neurons. Its levels are increasingly recognized as measures of neuroaxonal damage. The aim of this study was to explore serum neurofilament light chain (sNfL) levels in multiple sclerosis (MS) patients and healthy controls during pregnancy and puerperium. METHODS: This was a prospective, longitudinal, single-center study. sNfL concentration was assessed using a highly sensitive single-molecule array during pregnancy and in puerperium, in a cohort of 39 pregnant patients with relapsing multiple sclerosis (P-MS). Twenty-one healthy pregnant women (HPW) served as a control group. Eight P-MS suffered relapses during pregnancy (P-MS-R) in the first or second trimesters. RESULTS: No differences in pregnancy and delivery data were observed between P-MS and HPW. P-MS showed higher sNfL values than HPW in the first trimester, independently of the presence (P = 0.002) or not (P = 0.02) of relapses during pregnancy. However, in the third trimester, only P-MS-R showed higher sNfL values than HPW (P = 0.001). These differences extended to the puerperium, where P-MS-R showed higher sNfL values than those with no relapses during gestation (P = 0.02). CONCLUSION: These data strongly suggest that sNfL levels reflect MS activity during pregnancy. Additionally, the absence of relapses during pregnancy may have a beneficial effect on neurodegeneration during puerperium.

Genes differentially expressed by methylprednisolone in vivo in CD4 T lymphocytes from multiple sclerosis patients: potential biomarkers.

Intravenous methylprednisolone (IVMP) is the gold standard treatment in acute relapses of multiple sclerosis. Knowing the response to IVMP in advance could facilitate earlier selection of patients for subsequent courses of therapy. However, molecular mechanisms and changes in gene expression induced by methylprednisolone remain unknown. The aim of the study was to identify in vivo differentially expressed genes in relapsing-remitting multiple sclerosis patients after 3-6 days of treatment with IVMP. For this purpose, whole-genome transcription profiling of CD4+ T lymphocytes was performed before and after treatment with IVMP in 8 relapsing-remitting multiple sclerosis patients during relapse using Human GE 4x44K v2 microarrays. Differentially expressed genes were identified using a paired t test on GeneSpring v13.0 software. A P-value <0.001 and a twofold change were considered significant. Microarray data were confirmed using real-time PCR. Microarray revealed changes in gene expression: four genes were downregulated (B3GNT3, ZNF683, IFNG and TNF) and seven upregulated (DEFA4, CTSG, DEFA8P, AZU1, MPO, ELANE and PRTN3). Pathway analysis revealed the transforming growth factor-ß signaling pathway to be affected. Comparison with previously published data on in vitro methylprednisolone-regulated genes showed that SMAD7, TNF and CHI3L1 were also downregulated in vivo in relapsing-remitting multiple sclerosis patients. In summary, we performed the first in vivo transcriptome analysis in CD4+ T lymphocytes before and after the treatment with IVMP in patients with multiple sclerosis. Identification of differentially expressed genes in patients receiving IVMP could improve our understanding of the molecular mechanisms underlying the therapeutic effects of IVMP and highlight potential biomarkers of the response to IVMP.

Identificación de los factores que influyen en el retraso intrahospitalario del inicio de trombólisis intravenosa en el ictus agudo en un hospital terciario / Factors associated with in-hospital delays in treating acute stroke with intravenous thrombolysis in a tertiary centre

Objetivo: Identificar los factores que influyen en el tiempo puerta-aguja (tiempo P-A) en la administración de trombólisis intravenosa (TIV) en un hospital terciario para diseñar futuras estrategias que acorten los tiempos. Métodos: Estudio retrospectivo de pacientes tratados con TIV entre 2009 y 2012. Analizamos la relación entre el tiempo P-A y los siguientes factores: edad, sexo, antecedentes personales, tiempo inicio-puerta, activación de código ictus extrahospitalario (CIE), glucemia y presión arterial basal, NIHSS basal, realización de angio-TC o estudio neurosonológico previo, hora de llegada al hospital, día de la semana y año del ictus. Resultados: Hubo un total de 239 pacientes tratados. Tiempos de actuación en min (mediana [rango intercuartílico]): tiempo inicio-puerta 84 (60-120); tiempo puerta-TC 17 (13-24,75) tiempo TC-aguja 34 (26-47); tiempo puerta-aguja 52 (43-70); tiempo inicio-aguja 145 (120-180). El tiempo P-A fue significativamente menor con la activación del CIE: 51 vs. 72 (p = 0,008), y mayor con la realización de angio-TC: 59 vs. 48,5 (p = 0,004) y con tiempo inicio-puerta < 90 min: 58 vs. 48 (p = 0,003). En el análisis de regresión lineal múltiple 2 factores redujeron significativamente el tiempo P-A: la activación de CIE (reducción=26,3%; p < 0,001) y el tiempo inicio-puerta (por cada 30 min de tiempo inicio-puerta, el tiempo P-A se acortó 4,7 min; p = 0,02). Por el contrario realizar una angio-TC aumentó un 13,4% el tiempo P-A (p = 0,03). Los demás factores no influyeron significativamente en el tiempo P-A. Conclusiones: La realización de angio-TC y el «efecto de las 3 h» son 2 factores que retrasan el inicio de la TIV en nuestro hospital. Por el contrario el CIE reduce claramente los tiempos P-A. Los resultados de este estudio nos han permitido identificar qué factores retrasan nuestra actuación y servirán en un futuro para intentar disminuir los tiempos P-A en nuestro hospital

Objective: This study aims to determine which factors are associated with delays in door-to needle (DTN) time in our hospital. This will help us design future strategies to shorten time to treatment with intravenous thrombolysis (IVT). Methods: Retrospective analysis of a prospective cohort of patients with ischaemic stroke treated with IVT in our hospital between 2009 and 2012. We analysed the relationship between DTN time and the following variables: age, sex, personal medical history, onset-to-door time, pre-hospital stroke code activation, blood pressure and blood glucose level, National Institutes of Health Stroke Scale (NIHSS), computed tomography angiography (CTA) and/or doppler/duplex ultrasound (DUS) performed before IVT, time to hospital arrival, and day of the week and year of stroke. Results: Our hospital treated 239 patients. Median time to treatment in minutes (IQR): onset-to-door, 84 (60-120); door-to-CT, 17 (13-24.75); CT-to needle, 34 (26-47); door-to-needle, 52 (43-70); onset-to-needle, 145 (120-180). Door-to-needle time was significantly shorter when code stroke was activated, at 51 vs. 72 min (P = 0.008), and longer when CTA was performed, at 59 vs. 48.5 min (P = 0.004); it was also longer with an onset-to-door time < 90 min, at 58 vs. 48 min (P = 0.003). The multivariate linear regression analysis detected 2 factors affecting DTN: code stroke activation (26.3% reduction; P < 0.001) and onset-to-door time (every 30 min of onset-to-door delay corresponded to a 4.7min increase in DTN time [P = 0.02]). On the other hand, CTA resulted in a 13.4% increase in DTN (P = 0.03). No other factors had a significant influence on door-to-needle time. Conclusions: This study enabled us to identify CTA and the «3-hour effect» as the 2 factors that delay IVT in our hospital. In contrast, activating code stroke clearly reduces DTN. This information will be useful in our future attempts to reduce door-to-needle times

Factors associated with in-hospital delays in treating acute stroke with intravenous thrombolysis in a tertiary centre. / Identificación de los factores que influyen en el retraso intrahospitalario del inicio de trombólisis intravenosa en el ictus agudo en un hospital terciario.

OBJECTIVE: This study aims to determine which factors are associated with delays in door-to needle (DTN) time in our hospital. This will help us design future strategies to shorten time to treatment with intravenous thrombolysis (IVT). METHODS: Retrospective analysis of a prospective cohort of patients with ischaemic stroke treated with IVT in our hospital between 2009 and 2012. We analysed the relationship between DTN time and the following variables: age, sex, personal medical history, onset-to-door time, pre-hospital stroke code activation, blood pressure and blood glucose level, National Institutes of Health Stroke Scale (NIHSS), computed tomography angiography (CTA) and/or doppler/duplex ultrasound (DUS) performed before IVT, time to hospital arrival, and day of the week and year of stroke. RESULTS: Our hospital treated 239 patients. Median time to treatment in minutes (IQR): onset-to-door, 84 (60-120); door-to-CT, 17 (13-24.75); CT-to needle, 34 (26-47); door-to-needle, 52 (43-70); onset-to-needle, 145 (120-180). Door-to-needle time was significantly shorter when code stroke was activated, at 51 vs. 72min (P=0.008), and longer when CTA was performed, at 59 vs. 48.5min (P=0.004); it was also longer with an onset-to-door time<90min, at 58 vs. 48min (P=0.003). The multivariate linear regression analysis detected 2 factors affecting DTN: code stroke activation (26.3% reduction; P<0.001) and onset-to-door time (every 30min of onset-to-door delay corresponded to a 4.7min increase in DTN time [P=0.02]). On the other hand, CTA resulted in a 13.4% increase in DTN (P=0.03). No other factors had a significant influence on door-to-needle time. CONCLUSIONS: This study enabled us to identify CTA and the «3-hour effect¼ as the 2 factors that delay IVT in our hospital. In contrast, activating code stroke clearly reduces DTN. This information will be useful in our future attempts to reduce door-to-needle times.

Hematoma espinal epidural espontáneo: estudio retrospectivo de una serie de 13 casos / Spontaneous spinal epidural haematoma: A retrospective study of a series of 13 cases

Introducción: El hematoma espinal epidural espontáneo (HEEE) tiene una incidencia estimada de un caso por millón de habitantes al año. Se considera espontáneo cuando no se logra relacionar ninguna causa de forma directa con su aparición. Objetivo: Describir una muestra de pacientes con HEEE y analizar las variables relacionadas con el pronóstico funcional del mismo. Pacientes y métodos: Estudio retrospectivo de pacientes diagnosticados de HEEE en nuestro centro entre 2001 y 2013. Resultados: Trece pacientes, 7 varones, con edad media de 71 años. El 62% presentaba hipertensión arterial (HTA) y el 54% utilizaba anticoagulantes orales, teniendo una razón normalizada internacional > 3 el 57% de ellos. La presentación clínica más frecuente fue dolor en columna vertebral (85%). El 92% asoció déficit neurológico en forma de síndrome sensitivo-motor (70%), motor puro (15%) o sensitivo puro (7%). Cinco pacientes recibieron tratamiento quirúrgico y 8 fueron tratados de forma conservadora. Al año, 3 de los pacientes tratados de forma quirúrgica y 4 de los de manejo conservador tenían una puntuación igual o menor de 2 en la Escala Rankin Modificada. Se observó peor pronóstico en pacientes anticoagulados, en hematomas de mayor extensión, en hematomas localizados en región lumbar y cuando el compromiso motor inicial era mayor. Conclusiones: La edad avanzada, la HTA y la anticoagulación son los principales factores asociados con el HEEE. La presentación típica consiste en dolor en la columna vertebral seguido de déficit motor. En pacientes con déficits motores establecidos, el tratamiento quirúrgico dentro de las primeras 24 h parece ser la mejor opción terapéutica

Introduction: Spontaneous spinal epidural haematoma (SSEH) has an estimated incidence of one per million inhabitants. It is classified as spontaneous when no identifiable cause can be linked to its onset. Objective: To describe a sample of patients with SSEH and analyse variables related to its functional prognosis. Patients and methods: Retrospective study carried out in patients diagnosed with SSEH between 2001 and 2013 in our hospital. Results: We included 13 subjects (7 men) with a mean age of 71 years. Of the total, 62% had hypertension and 54% were treated with oral anticoagulants; of the latter, 57% had an International Normalised Ratio above 3. The most frequent manifestation was spinal column pain (85%). Nearly all subjects presented an associated neurological deficit, whether sensory-motor (70%), pure motor (15%), or pure sensory (7%). Five patients underwent surgical treatment and 8 had conservative treatment. After one year, 3 of the patients treated surgically and 4 of those on conservative treatment had a score of 2 or lower on the modified Rankin Scale. Poorer prognosis was observed in patients with anticoagulant therapy, large haematomas, location in the lumbar region, and more pronounced motor disability at onset. Conclusions: Old age, hypertension, and anticoagulant therapy are the main risk factors for SSEH. The typical presentation consists of back pain with subsequent motor deficit. In patients with established motor symptoms, surgical treatment within the first 24 hours seems to be the best option

Spontaneous spinal epidural haematoma: a retrospective study of a series of 13 cases.

INTRODUCTION: Spontaneous spinal epidural haematoma (SSEH) has an estimated incidence of one per million inhabitants. It is classified as spontaneous when no identifiable cause can be linked to its onset. OBJECTIVE: To describe a sample of patients with SSEH and analyse variables related to its functional prognosis. PATIENTS AND METHODS: Retrospective study carried out in patients diagnosed with SSEH between 2001 and 2013 in our hospital. RESULTS: We included 13 subjects (7 men) with a mean age of 71 years. Of the total, 62% had hypertension and 54% were treated with oral anticoagulants; of the latter, 57% had an International Normalised Ratio above 3. The most frequent manifestation was spinal column pain (85%). Nearly all subjects presented an associated neurological deficit, whether sensory-motor (70%), pure motor (15%), or pure sensory (7%). Five patients underwent surgical treatment and 8 had conservative treatment. After one year, 3 of the patients treated surgically and 4 of those on conservative treatment had a score of 2 or lower on the modified Rankin Scale. Poorer prognosis was observed in patients with anticoagulant therapy, large haematomas, location in the lumbar region, and more pronounced motor disability at onset. CONCLUSIONS: Old age, hypertension, and anticoagulant therapy are the main risk factors for SSEH. The typical presentation consists of back pain with subsequent motor deficit. In patients with established motor symptoms, surgical treatment within the first 24hours seems to be the best option.

Labor asistencial del equipo de guardia de neurología en un hospital terciario de Madrid: análisis prospectivo durante un año / Workload of on-call emergency room neurologists in a Spanish tertiary care centre. A one-year prospective study

Introducción: El envejecimiento poblacional, el aumento en la demanda asistencial y la instauración de tratamientos avanzados para el ictus agudo han originado que las urgencias neurológicas crezcan en número y complejidad. A pesar de esto, muchos centros hospitalarios de España carecen de guardias específicas de Neurología. Métodos: Estudio prospectivo durante un año (agosto 2010-julio 2011), que describe la labor asistencial del equipo de guardia de Neurología del Hospital terciario Gregorio Marañón de Madrid. Se recogieron las características sociodemográficas, las principales afecciones, las pruebas diagnósticas y el flujo de los pacientes atendidos, utilizando un registro diario mediante una base de datos informatizada. Los resultados fueron comparados con la asistencia médica general en urgencias. Resultados: Se atendió a 3.234 pacientes (3,48% del total de urgencias médicas), con una media de 11,15 pacientes/día. La edad media fue de 59 años. Las enfermedades más frecuentes fueron la cerebrovascular (34%), epilepsia (16%) y cefalea (8%). La estancia media en urgencias fue de 7,17 h. La tasa de ingreso hospitalario fue del 40% (7,38% del total de ingresos urgentes por afección médica). Los principales destinos de los pacientes hospitalizados fueron Unidad de Ictus (39,5%) y la planta de Neurología (33%). Se realizaron 76 procedimientos trombolíticos o intravasculares en ictus agudos. El 70% de los pacientes fue valorado fuera del horario laboral. Conclusiones: La atención neurológica es frecuente, variada y compleja, representando un alto porcentaje sobre el total de paciente atendidos o ingresados en urgencias. Nuestros resultados justifican la presencia física de un neurólogo de guardia 24 h en urgencias

Introduction: Population ageing, the rising demand for healthcare, and the establishment of acute stroke treatment programs have given rise to increases in the number and complexity of neurological emergency cases. Nevertheless, many centres in Spain still lack on-call emergency neurologists. Methods: We conducted a retrospective study to describe the role of on-call neurologists at Hospital General Universitario Gregorio Marañon, a tertiary care centre in Madrid, Spain. Sociodemographic characteristics, most common pathologies, diagnostic tests, and destination of the patients attended were recorded daily using a computer database. Results were compared with the general care data from the emergency department. Results: The team attended 3234 patients (3.48% of the emergency department total). The mean number of patients seen per day was 11.15. The most frequent pathologies were stroke (34%), epilepsy (16%) and headache (8%). The mean stay in the emergency department was 7.17 hours. Hospital admission rate was 40% (7.38% of emergency hospital admissions). The main destinations for admitted patients were the stroke unit (39.5%) and the neurology department (33%). Endovascular or thrombolytic therapies were performed on 76 occasions. Doctors attended 70% of the patients during on-call hours. Conclusions: Emergency neurological care is varied, complex, and frequently necessary. Neurological cases account for a sizeable percentage of both patient visits to the emergency room and the total number of emergency admissions. The current data confirm that on-call neurologists available on a 24-hour basis are needed in emergency departments

Workload of on-call emergency room neurologists in a Spanish tertiary care centre. A one-year prospective study.

INTRODUCTION: Population ageing, the rising demand for healthcare, and the establishment of acute stroke treatment programs have given rise to increases in the number and complexity of neurological emergency cases. Nevertheless, many centres in Spain still lack on-call emergency neurologists. METHODS: We conducted a retrospective study to describe the role of on-call neurologists at Hospital General Universitario Gregorio Marañón, a tertiary care centre in Madrid, Spain. Sociodemographic characteristics, most common pathologies, diagnostic tests, and destination of the patients attended were recorded daily using a computer database. Results were compared with the general care data from the emergency department. RESULTS: The team attended 3234 patients (3.48% of the emergency department total). The mean number of patients seen per day was 11.15. The most frequent pathologies were stroke (34%), epilepsy (16%) and headache (8%). The mean stay in the emergency department was 7.17 hours. Hospital admission rate was 40% (7.38% of emergency hospital admissions). The main destinations for admitted patients were the stroke unit (39.5%) and the neurology department (33%). Endovascular or thrombolytic therapies were performed on 76 occasions. Doctors attended 70% of the patients during on-call hours. CONCLUSIONS: Emergency neurological care is varied, complex, and frequently necessary. Neurological cases account for a sizeable percentage of both patient visits to the emergency room and the total number of emergency admissions. The current data confirm that on-call neurologists available on a 24-hour basis are needed in emergency departments.