Comparing RNA extraction methods to face the variations in RNA quality using two human biological matrices.

BACKGROUND: Nucleic acids, RNA among them, are widely used in biomedicine and Biotechnology. Because of their susceptibility to degradation by RNases, the handling and extraction process of RNA from cells and tissues require specialized personnel and standardized methods to guarantee high purity and integrity. Due to the diversity of techniques found in the market, a comparative study between different RNA extraction methods is useful to facilitate the best choice for the researcher or in research service platforms such as biobanks to see the traceability of the samples. METHODS AND RESULTS: In this study, we have compared seven different RNA extraction methods: manual (TRIzol™), semiautomated (QIAGEN™, Bio-Rad, Monarch®, and Canvax™), and fully automated (QIAcube™ and Maxwell®) processes, from two biological matrices: human Jurkat T cells and peripheral blood mononuclear cells (PBMC). Results showed marked differences in the RNA quality and functionality according to the method employed for RNA extraction and the matrix used. DISCUSSION: QIAcube™ and semi-automated extraction methods were perceived as the best options because of their lower variability, good functionality, and lower cost (P < 0.001). These data contribute to facilitating researchers or research service platforms (Biobanks) in decision-making practices and emphasize the relevance of the selection of the RNA extraction method in each experimental procedure or traceability study to guarantee both quality standards and its reproducibility.

Environmental exposure to pesticides and Amyotrophic Lateral Sclerosis in the South of Spain.

OBJECTIVE: To determine if there is a relationship between environmental exposure to pesticides and the prevalence of Amyotrophic Lateral Sclerosis (ALS) in Andalusia. METHOD: We carried out a case-control study using the logistic regression method to verify the relationship between the prevalence of ALS in the area exposed to pesticides versus the unexposed area, through the Odds Ratio statistical test. RESULTS: The study population consisted of 519 individuals diagnosed with ALS between January 2016 and December 2018 according to the CMBD (Minimum Basic Data Set) as cases. In the control group, we have 8,384,083 individuals obtained from data from the National Institute of Statistics (INE). The Odds Ratio (OR) was used as a measure of association between cases and controls, obtaining an OR between 0.76 and 1.08 for the confidence interval of the CI (95%). CONCLUSIONS: Despite the existence of various studies that suggest a possible association between environmental exposure to pesticides and the risk of Amyotrophic Lateral Sclerosis, our analysis of the Andalusian population did not find significant evidence of this association.

Environmental exposure to pesticides and Amyotrophic Lateral Sclerosis in the South of Spain / Exposición ambiental a pesticidas y esclerosis lateral amiotrófica en el sur de España

Objective: To determine if there is a relationship between environmental exposure to pesticides and the prevalence of Amyotrophic Lateral Sclerosis (ALS) in Andalusia. Method: We carried out a case–control study using the logistic regression method to verify the relationship between the prevalence of ALS in the area exposed to pesticides versus the unexposed area, through the Odds Ratio statistical test. Results: The study population consisted of 519 individuals diagnosed with ALS between January 2016 and December 2018 according to the CMBD (Minimum Basic Data Set) as cases. In the control group, we have 8,384,083 individuals obtained from data from the National Institute of Statistics (INE). The Odds Ratio (OR) was used as a measure of association between cases and controls, obtaining an OR between 0.76 and 1.08 for the confidence interval of the CI (95%). Conclusions: Despite the existence of various studies that suggest a possible association between environmental exposure to pesticides and the risk of Amyotrophic Lateral Sclerosis, our analysis of the Andalusian population did not find significant evidence of this association.(AU)

Objetivo: Analizar si existe una relación entre la exposición ambiental a pesticidas y la prevalencia de esclerosis lateral amiotrófica (ELA) en Andalucía. Métodos: Realizamos un estudio de casos y controles con regresión logística para esclarecer la relación entre la prevalencia de ELA en el área expuesta a pesticidas vs. el área sin exposición, mediante el cálculo de razón de probabilidades (odds ratio [OR]). Resultados: Incluimos un grupo de casos, con 519 individuos diagnosticados de ELA entre enero de 2016 y diciembre de 2018, obtenidos del conjunto mínimo básico de datos, y un grupo control con 8.384.083 individuos obtenidos de la base de datos del Instituto Nacional de Estadística. Se utilizó la OR para medir la asociación entre casos y controles, con un intervalo de confianza del 95% de 0,76-1,08. Conclusiones: A pesar de que varios estudios sugieren una posible asociación entre la exposición ambiental a pesticidas y un aumento en el riesgo de ELA, nuestro estudio sobre la población andaluza no halló datos significativos en favor de dicha hipótesis.(AU)

Functional outcomes of patients with NORSE and FIRES treated with immunotherapy: A systematic review.

OBJECTIVE: To determine the frequency of good functional outcomes in patients with NORSE and FIRES treated with immunotherapy. METHODS: We performed a systematic search of the MedLine and EMBASE databases to gather studies including at least 5 patients with NORSE or FIRES and at least one patient treated with immunotherapy, and reporting functional outcomes. Good functional outcome was defined as a modified Rankin Scale (mRS) score ≤ 2 (or an equivalent measure) at the last available follow-up assessment. Only patients with known functional outcomes were included in the analysis. RESULTS: We analyzed 16 studies including a total of 161 patients with NORSE. Six studies were carried out only with FIRES patients (n = 64). Of the 161 patients with NORSE, 141 (87.5%) received immunotherapy. Outcome data were available for 135, 56 of whom (41.4%) achieved good functional outcomes. Twenty-four of the 58 patients with FIRES treated with immunotherapy and for whom outcome data were available achieved good functional outcomes (41.3%). Mortality rates in patients with NORSE and FIRES treated with immunotherapy were 20/121 (16.5%) and 6/58 (10.3%), respectively. By type of immunotherapy, good functional outcomes were achieved in 36/89 patients receiving glucocorticoids (40.4%), 27/71 patients receiving IV immunoglobulins (38%), 11/37 patients treated with plasma exchange (29.7%), 5/17 patients receiving rituximab (29.4%), and 2/13 patients receiving cyclophosphamide (15.3%). CONCLUSION: Despite the lack of randomised clinical trials, immunotherapy is frequently prescribed to patients with NORSE and FIRES. However, rates of functional dependence and mortality remain high in these patients. Second-line therapies achieved lower rates of good outcomes, probably because they were administered to patients with more severe, refractory disease.

Fracaso de un anticuerpo monoclonal anti-CGRP en el tratamiento de la migraña. ¿Tiene sentido probar otro? / Failure of an anti-CGRP monoclonal antibody in the treatment of migraine. Is it worthwhile trying another one?

Introducción: La migraña es una enfermedad neurológica altamente prevalente y la búsqueda de un tratamiento eficaz que mejore la calidad de vida del paciente es fundamental. En 2018 se aprobaron en España los anticuerpos monoclonales anti-CGRP como tratamiento preventivo, y han demostrado eficacia al reducir el número de crisis de migraña al mes frente a placebo. Pacientes y métodos: Estudio descriptivo y retrospectivo de 14 pacientes con migraña episódica de alta frecuencia y crónica, en seguimiento en nuestra unidad de cefaleas, en los que se ha realizado el cambio de un monoclonal anti-CGRP por ineficacia. Se han recogido datos epidemiológicos y variables relacionadas con la respuesta a ambos fármacos, como los días de cefalea al mes y los días de migraña al mes, además de escalas validadas de calidad de vida (Migraine Disability Assessment Scale y Headache Impact Test-6). Resultados: El 50% de los pacientes son varones, con una mediana de edad de 46,5, y el 92% estaba diagnosticado de migraña crónica. Se realizó un seguimiento de entre seis y 12 meses tras el cambio de tratamiento en el 91,6%, y se observó mejoría significativa en el 33% de los pacientes. Además, en el 50% se objetivó respuesta inicial tras tres dosis con el primer monoclonal. Conclusiones: En nuestra serie, el 66% de los pacientes que no respondieron a un primer fármaco respondió inicialmente al cambio, y esta mejoría se mantuvo en el 36%. Se precisan estudios más amplios para aclarar esta diferencia de respuesta a los distintos anticuerpos monoclonales anti-CGRP.(AU)

Introduction: Migraine is a highly prevalent neurological disease and the search for an effective treatment to improve the patient’s quality of life is essential. In 2018, anti-CGRP monoclonal antibodies were approved in Spain as a preventive treatment, and have proved to be effective in reducing the number of migraine crisis per month compared to placebo. Patients and methods: We conducted a descriptive and retrospective study of 14 patients suffering from high-frequency or chronic episodic migraine, under follow-up in our headache unit, in whom an anti-CGRP monoclonal was changed due to its ineffectiveness. Epidemiological data and variables related to the response to both drugs were collected, such as headache days per month and migraine days per month, as well as validated quality of life scales (Migraine Disability Assessment Scale and Headache Impact Test-6). Results: 50% of patients were males, with a median age of 46.5 years and 92% were diagnosed with chronic migraine. A follow-up of 6 to 12 months after the change of treatment was performed in 91.6% and significant improvement was observed in 33% of the patients. In addition, 50% had an initial response after three doses of the first monoclonal drug. Conclusions: In our series, 66% of patients who did not respond to a first drug responded initially to the switch and this improvement was maintained in 36% of them. Larger studies are needed to clarify this difference in response to different anti-CGRP monoclonal antibodies.(AU)

[Failure of an anti-CGRP monoclonal antibody in the treatment of migraine. Is it worthwhile trying another one?] / Fracaso de un anticuerpo monoclonal anti-CGRP en el tratamiento de la migraña. ¿Tiene sentido probar otro?

INTRODUCTION: Migraine is a highly prevalent neurological disease and the search for an effective treatment to improve the patient's quality of life is essential. In 2018, anti-CGRP monoclonal antibodies were approved in Spain as a preventive treatment, and have proved to be effective in reducing the number of migraine crisis per month compared to placebo. PATIENTS AND METHODS: We conducted a descriptive and retrospective study of 14 patients suffering from high-frequency or chronic episodic migraine, under follow-up in our headache unit, in whom an anti-CGRP monoclonal was changed due to its ineffectiveness. Epidemiological data and variables related to the response to both drugs were collected, such as headache days per month and migraine days per month, as well as validated quality of life scales (Migraine Disability Assessment Scale and Headache Impact Test-6). RESULTS: 50% of patients were males, with a median age of 46.5 years and 92% were diagnosed with chronic migraine. A follow-up of 6 to 12 months after the change of treatment was performed in 91.6% and significant improvement was observed in 33% of the patients. In addition, 50% had an initial response after three doses of the first monoclonal drug. CONCLUSIONS: In our series, 66% of patients who did not respond to a first drug responded initially to the switch and this improvement was maintained in 36% of them. Larger studies are needed to clarify this difference in response to different anti-CGRP monoclonal antibodies.

TITLE: Fracaso de un anticuerpo monoclonal anti-CGRP en el tratamiento de la migraña. ¿Tiene sentido probar otro?Introducción. La migraña es una enfermedad neurológica altamente prevalente y la búsqueda de un tratamiento eficaz que mejore la calidad de vida del paciente es fundamental. En 2018 se aprobaron en España los anticuerpos monoclonales anti-CGRP como tratamiento preventivo, y han demostrado eficacia al reducir el número de crisis de migraña al mes frente a placebo. Pacientes y métodos. Estudio descriptivo y retrospectivo de 14 pacientes con migraña episódica de alta frecuencia y crónica, en seguimiento en nuestra unidad de cefaleas, en los que se ha realizado el cambio de un monoclonal anti-CGRP por ineficacia. Se han recogido datos epidemiológicos y variables relacionadas con la respuesta a ambos fármacos, como los días de cefalea al mes y los días de migraña al mes, además de escalas validadas de calidad de vida (Migraine Disability Assessment Scale y Headache Impact Test-6). Resultados. El 50% de los pacientes son varones, con una mediana de edad de 46,5, y el 92% estaba diagnosticado de migraña crónica. Se realizó un seguimiento de entre seis y 12 meses tras el cambio de tratamiento en el 91,6%, y se observó mejoría significativa en el 33% de los pacientes. Además, en el 50% se objetivó respuesta inicial tras tres dosis con el primer monoclonal. Conclusiones. En nuestra serie, el 66% de los pacientes que no respondieron a un primer fármaco respondió inicialmente al cambio, y esta mejoría se mantuvo en el 36%. Se precisan estudios más amplios para aclarar esta diferencia de respuesta a los distintos anticuerpos monoclonales anti-CGRP.

Environmental exposure to pesticides and Amyotrophic Lateral Sclerosis in the South of Spain.

OBJECTIVE: To determine if there is a relationship between environmental exposure to pesticides and the prevalence of Amyotrophic Lateral Sclerosis (ALS) in Andalusia. METHOD: We carried out a case-control study using the logistic regression method to verify the relationship between the prevalence of ALS in the area exposed to pesticides versus the unexposed area, through the Odds Ratio statistical test. RESULTS: The study population consisted of 519 individuals diagnosed with ALS between January 2016 and December 2018 according to the CMBD (Minimum Basic Data Set) as cases. In the control group, we have 8,384,083 individuals obtained from data from the National Institute of Statistics (INE). The Odds Ratio (OR) was used as a measure of association between cases and controls, obtaining an OR between 0.76 and 1.08 for the confidence interval of the CI (95%). CONCLUSIONS: Despite the existence of various studies that suggest a possible association between environmental exposure to pesticides and the risk of Amyotrophic Lateral Sclerosis, our analysis of the Andalusian population did not find significant evidence of this association.

Case fatality of COVID-19 in patients with neurodegenerative dementia. / Análisis de letalidad por COVID-19 en pacientes con demencia neurodegenerativa.

INTRODUCTION: The elderly population is the group most threatened by COVID-19, with the highest mortality rates. This study aims to analyse the case fatality of COVID-19 in a cohort of patients with degenerative dementia. METHODS: We conducted a descriptive case-control study of a sample of patients diagnosed with primary neurodegenerative dementia. RESULTS: Twenty-four of the 88 patients with COVID-19 included in the study died: 10/23 (43.4%) patients diagnosed with dementia and 14/65 (21.5%) controls; this difference was statistically significant. DISCUSSION: Our results suggest that case fatality of COVID-19 is significantly higher among patients with primary degenerative dementia than in other patients with similar mean ages and comorbidities.

Miller-Fisher syndrome after SARS-CoV-2 infection.

INTRODUCTION: On March 11th, 2020, the WHO declared the SARS-Cov-2 pandemic. Syndromes have been detected in relation to COVID-19 such as encephalitis, acute necrotizing hemorrhagic encephalopathy and cerebrovascular complications. There are also cases of peripheral nervous system involvement. METHODS: Our case would be the 3rd patient with MFS associated with COVID-19 as far as we know. RESULTS: We present a 51 years old female diagnosed with MFS two weeks after COVID-19. RTPCR to SARS-CoV-2 was negative but IgG was positive. CONCLUSION: Most of the cases were mild or moderate with typical signs and symptoms. All were treated with IV immunoglobulin with good response in most cases. Despite the short evolution time of the cases surviving the current pandemic, the description of cases of post-infectious neurological syndromes suggests that this is probably not an infrequent complication in the subacute stage of Covid-19 disease.

Impact of SARS-CoV-2 infection on neurodegenerative and neuropsychiatric diseases: a delayed pandemic? / Influencia de la infección SARS-CoV-2 sobre enfermedades neurodegenerativas y neuropsiquiátricas: ¿una pandemia demorada?

INTRODUCTION: SARS-CoV-2 was first detected in December 2019 in the Chinese city of Wuhan and has since spread across the world. At present, the virus has infected over 1.7 million people and caused over 100 000 deaths worldwide. Research is currently focused on understanding the acute infection and developing effective treatment strategies. In view of the magnitude of the epidemic, we conducted a speculative review of possible medium- and long-term neurological consequences of SARS-CoV-2 infection, with particular emphasis on neurodegenerative and neuropsychiatric diseases of neuroinflammatory origin, based on the available evidence on neurological symptoms of acute SARS-CoV-2 infection. DEVELOPMENT: We systematically reviewed the available evidence about the pathogenic mechanisms of SARS-CoV-2 infection, the immediate and lasting effects of the cytokine storm on the central nervous system, and the consequences of neuroinflammation for the central nervous system. CONCLUSIONS: SARS-CoV-2 is a neuroinvasive virus capable of triggering a cytokine storm, with persistent effects in specific populations. Although our hypothesis is highly speculative, the impact of SARS-CoV-2 infection on the onset and progression of neurodegenerative and neuropsychiatric diseases of neuroinflammatory origin should be regarded as the potential cause of a delayed pandemic that may have a major public health impact in the medium to long term. Cognitive and neuropsychological function should be closely monitored in COVID-19 survivors.

Will neurological care change over the next 5 years due to the COVID-19 pandemic? Key informant consensus survey. / ¿Va a cambiar la neurología tras la pandemia de COVID-19 en los próximos 5 años? Estudio de enfoque mediante informadores clave.

INTRODUCTION: The COVID-19 pandemic will give rise to long-term changes in neurological care, which are not easily predictable. MATERIAL AND METHODS: A key informant survey was used to enquire about the changes expected in the specialty over the next 5 years. The survey was completed by heads of neurology departments with broad knowledge of the situation, having been active during the pandemic. RESULTS: Despite a low level of consensus between participants, there was strong (85%) and moderate consensus (70%) about certain subjects, mainly the increase in precautions to be taken, the use of telemedicine and teleconsultations, the reduction of care provided in in-person consultations to avoid the presence of large numbers of people in waiting rooms, the development of remote training solutions, and the changes in monitoring visits during clinical trials. There was consensus that there would be no changes to the indication of complementary testing or neurological examination. CONCLUSION: The key informant survey identified the foreseeable changes in neurological care after the pandemic.

Estudio observacional multicéntrico español sobre el empleo de fármacos antiepilépticos en consultas de neurología / Observational multicentre study into the use of antiepileptic drugs in Spanish neurology consultations

OBJETIVO: Cuantificar el tipo de fármacos antiepilépticos (FAE) empleados en epilepsia, en consultas de neurología. MATERIAL Y MÉTODO: Estudio descriptivo observacional sobre una muestra de 559 pacientes mayores de 14 años con epilepsia y en tratamiento farmacológico, recogidos en consultas ambulatorias por 47 neurólogos en España en mayo del año 2016. Para las clasificaciones clínicas de la epilepsia se utilizaron las de la Liga Internacional contra la Epilepsia (ILAE). Los FAE se clasificaron según el año de comercialización: clásicos (anteriores al 1990) y nuevos (los posteriores). Se realiza un análisis descriptivo de las variables cualitativas y cuantitativas. RESULTADOS: Demográficos: 54,6% mujeres; edad media 42,7 años; edad media de inicio de la epilepsia 22,4 años. Clínicos: predominan las crisis parciales: 75,7%; sintomáticas: 51,5% y con epilepsia farmacorresistente: 32,4%. Pacientes libres de crisis en el último año: 35,6%. Comorbilidad asociada: 59,2%. Tratamiento: número de FAE empleados 1103; 64,6% FAE nuevos. El 85,4% de los pacientes tratados con FAE nuevos. La media y el rango de FAE empleados: 2 (1-5). El 59,6% recibía politerapia. Los FAE más utilizados: levetiracetam (LEV) 42,6%, ácido valproico (VPA) 25,4%, lamotrigina 19,5%, carbamacepina 17,9% y lacosamida 17,5%. Ningún FAE fue empleado exclusivamente en monoterapia. El más utilizado en crisis generalizadas fue el VPA (48,2%) y en parciales, el LEV (43,2%). El VPA fue menos utilizado en mujeres. Los pacientes sin control de sus crisis (48,7%) o con comorbilidad asociada (45,6%) recibían la combinación de ambos tipos de FAE, en mayor porcentaje, que de forma aislada. CONCLUSIONES: La mayoría de los pacientes toman FAE nuevos. La asociación de ambos tipos de FAE se emplea en mayor medida en los pacientes sin control de sus crisis o con comorbilidad asociada

INTRODUCTION: The study aims to quantify the types of antiepileptic drugs (AED) prescribed in neurology consultations. MATERIAL AND METHOD: This descriptive, observational study included a sample of 559 patients older than 14 years, diagnosed with epilepsy, and receiving pharmacological treatment. Data were collected at outpatient consultations by 47 Spanish neurologists in May 2016. Epilepsy was defined based on the International League Against Epilepsy classification. According to the year of marketing, AEDs were categorised as classic (before 1990) or new (after 1990). We performed a descriptive analysis of qualitative and quantitative variables. RESULTS: Female patients accounted for 54.6% of the sample. Mean age was 42.7 years; mean age of onset was 22.4. Regarding epilepsy type, 75.7% of patients experienced partial seizures, 51.5% were symptomatic,32.4% had refractory epilepsy, 35.6% had been seizure-free for the previous year, and 59.2% had associated comorbidities.A total of 1103 AED prescriptions were made; 64.6% of prescriptions were for new AEDs; 85.4% of patients received new AEDs. Patients received a mean of 2 AEDs (range, 1-5). A total of 59.6% of patients received polytherapy.The most frequently prescribed AEDs were levetiracetam (42.6%), valproic acid (25.4%), lamotrigine (19.5%), carbamazepine (17.9%), and lacosamide (17.5%). No AED was employed exclusively as monotherapy. The most frequently prescribed AEDs for generalised and partial seizures were valproic acid (48.2%) and levetiracetam (43.2%), respectively. Valproic acid was less frequently prescribed to female patients. Patients with refractory epilepsy or with associated comorbidities were more frequently prescribed a combination of new and classic AEDs (48.7% and 45.6%, respectively) than only one type of AED. CONCLUSIONS: The majority of patients received new AEDs. The combination of classic and new AEDs was more frequently prescribed to patients with refractory epilepsy or with associated comorbidities

Observational multicentre study into the use of antiepileptic drugs in Spanish neurology consultations. / Estudio observacional multicéntrico español sobre el empleo de fármacos antiepilépticos en consultas de neurología.

INTRODUCTION: The study aims to quantify the types of antiepileptic drugs (AED) prescribed in neurology consultations. MATERIAL AND METHOD: This descriptive, observational study included a sample of 559 patients older than 14 years, diagnosed with epilepsy, and receiving pharmacological treatment. Data were collected at outpatient consultations by 47 Spanish neurologists in May 2016. Epilepsy was defined based on the International League Against Epilepsy classification. According to the year of marketing, AEDs were categorised as classic (before 1990) or new (after 1990). We performed a descriptive analysis of qualitative and quantitative variables. RESULTS: Female patients accounted for 54.6% of the sample. Mean age was 42.7 years; mean age of onset was 22.4. Regarding epilepsy type, 75.7% of patients experienced partial seizures, 51.5% were symptomatic,32.4% had refractory epilepsy, 35.6% had been seizure-free for the previous year, and 59.2% had associated comorbidities.A total of 1103 AED prescriptions were made; 64.6% of prescriptions were for new AEDs; 85.4% of patients received new AEDs. Patients received a mean of 2 AEDs (range, 1-5). A total of 59.6% of patients received polytherapy.The most frequently prescribed AEDs were levetiracetam (42.6%), valproic acid (25.4%), lamotrigine (19.5%), carbamazepine (17.9%), and lacosamide (17.5%). No AED was employed exclusively as monotherapy. The most frequently prescribed AEDs for generalised and partial seizures were valproic acid (48.2%) and levetiracetam (43.2%), respectively. Valproic acid was less frequently prescribed to female patients. Patients with refractory epilepsy or with associated comorbidities were more frequently prescribed a combination of new and classic AEDs (48.7% and 45.6%, respectively) than only one type of AED. CONCLUSIONS: The majority of patients received new AEDs. The combination of classic and new AEDs was more frequently prescribed to patients with refractory epilepsy or with associated comorbidities.