Background of the Sociedad Neurológica Argentina: Current state and concerns about neurologic education

Neurology in Argentina emerged toward the end of the 19th century, following the origin of the specialty in Europe. Its development can be divided into 3 periods. The first is the specialty of neurology as part of internal medicine. Doctoral theses and publication about neurologic topics are found early in the history of medicine, but merged into internal medicine. The second period is the foundation of clinical neurology under the typical European influence, mainly French, when the first neurologists appear. This period started in 1885 with the creation of the Hospital San Roque de Buenos Aires' first nervous diseases department. Its first chair was José María Ramos Mejía, MD. In 1887, 5 years after Jean-Martin Charcot was awarded the chair of neurology at the Salpêtrière in Paris, Ramos Mejía became the first professor of neurology in South America, at the University of Buenos Aires. The third period is the emergence of subspecialty practices. During the 1970s—reflecting the North American influence—there was a new paradigm favoring the division of different disciplines. Specialists in epilepsy, stroke, headache, dementia, and multiple sclerosis, among others, began to emerge.Fil: Correale, Jorge. Fundación Para la Lucha Contra las Enfermedades Neurológicas de la Infancia. Instituto de Investigaciones Neurológicas "Raúl Carrea"; ArgentinaFil: Allegri, Ricardo Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Centro Neurológico Tucumán. Departamento de Neurología; ArgentinaFil: Pelli Noble, Raúl Federico. Fundación Para la Lucha Contra las Enfermedades Neurológicas de la Infancia. Instituto de Investigaciones Neurológicas "Raúl Carrea"; Argentin

A plain language summary on assessing the long-term effectiveness of cladribine tablets in people living with relapsing multiple sclerosis: The CLASSIC-MS study

Cladribina; Multiple sclerosis; RelapsesCladribina; Esclerosi múltiple; RecaigudesCladribina; Esclerosis múltiple; RecaídasWhat is this summary about? Previous studies have shown that people living with multiple sclerosis (MS) treated with cladribine tablets have fewer relapses (where new symptoms occur or existing symptoms get worse for 24 hours or more) and delayed disability progression (slowing down of the disease getting worse). The CLASSIC-MS study looked at the long-term effectiveness of treatment with cladribine tablets in people living with MS who had taken part in the original CLARITY and CLARITY Extension clinical studies. What were the results? Results showed that people treated with cladribine tablets maintained their mobility (the ability to move freely) for longer and experienced other positive effects long after their treatment ended, including being less likely to need further treatment for their MS. What do the results mean? The results obtained from CLASSIC-MS show that the benefits of taking cladribine tablets carry on even when patients stop taking the treatment

Changes in the Care of Neurological Diseases During the First Wave of the COVID-19 Pandemic: A Single Private Center Study in Argentina

Introduction: Healthcare systems are struggling to cope with the rapid evolution of the COVID-19 pandemic. In Argentina, the pandemic is advancing despite prolonged lockdown measures. We aim to analyze the impact of the easing of lockdown measures in the number of visits to the emergency department (ED), and outpatient consultations (OC) to a tertiary neurological center. Methods: We compared the number of ED visits with the social mobility overtime. We also compared the number of OC, and the geographic distribution of patients' addresses between 2019 and 2020. Results: ED visits decreased 48.33% (n = 14,697 in 2019 vs. n = 7,595 in 2020). At the beginning of the lockdown, the social mobility decreased in pharmacies/groceries, and workplaces, along with a reduction in the number of ED visits. With the easing of lockdown restrictions, the social mobility decreased in residential places, slightly increased in workplaces and almost return to normal in pharmacies/groceries. Variations in ED visits correlate better with social mobility in workplaces (coef. =0.75, p < 0.001) than in groceries/pharmacies (coef. =0.68, p < 0.001). OC decreased 43%. Fourteen percent of OC were tele consults. This was associated with an increase of the geographical area of influence of our center (standard distance of 109 km in 2019 and 127 km in 2020). Conclusions: Despite an increase in social mobility, the number of ED visits and OC to an Argentinian tertiary neurological center remain worrisomely low. The pandemic catalyzed the introduction of telemedicine in our country. This has also allowed patients from distant zones to gain access to specialized neurological care.Fil: Calandri, Ismael L.. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Hawkes, Maximiliano Alberto. University of Nebraska; Estados UnidosFil: Marrodan, Mariano. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Ameriso, Sebastian Francisco. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Correale, Jorge. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Allegri, Ricardo Francisco. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia. Instituto de Neurociencias - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Neurociencias; Argentin

The impact of an early strict nationwide lockdown on the pattern of consultation for neurological diseases

A massive disruption of healthcare systems, a profound economic depressionand a distressing social situation [1]. Most countries enteredinto a lockdown in an attempt to slow the spread of the virus once theywere already suffering a serious hit. Based on the experience observed in Europe, Argentina closed its borders on March 15thonly one week afterthe firstperson died of COVID-19, and implemented an early nationwidelockdown limiting the circulation of 90% of its population, on March20th, with 128 cases and 3 deaths of COVID-19 [2-3]. Most health careresources were reassigned in anticipation of a catastrophic situation. Themassive communication media and the medical community warned thepopulation about the necessity of avoiding ?non-urgent? consults to theemergency rooms to avoid the overload of the system.To evaluate the impact of the national lockdown policy during theCOVID-19 pandemic,we compared the pattern of consultation to a tertiaryneurological center.Patients who attended to our ED have primaryneurological complaints or presented chronic neurological conditionswith varied medical problems. The period evaluated was the quarantineperiod (March 20st to April 26th 2020) with the same timeframeof 2019.Descriptive summaries are presented as mean or median (standarddeviation, SD) for continuous variables and proportions for categoricalvariables. The t-test or Mann-Whitney test were used to comparequantitative variables as appropriate. Pearson Chi-Square test or Fisher´sexact test were used to comparefrequencies of categorical variables asappropriate.A p-value < 0.05 was considered significant. The statisticalanalysis was performed with R-3.6.1, and the tydiverse, ggpubr, andggplot2 packages. This research has been approved by the Institutional Ethics Committee.Fil: Calandri, I.L.. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Hawkes, Maximiliano Alberto. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Marrodán, María Dolores. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Ameriso, Sebastian Francisco. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Correale, Jorge. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Allegri, Ricardo Francisco. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

La Cognición Social en la Esclerosis Múltiple Temprana: Enfoque neuropsicológico y anatómico

Cognitive impairment and deficits in social cognition (SC) are frequent in patients with multiple sclerosis (MS). The aim of the present work is to study SC in patients with early MS and to analyze its neuroanatomical correlation. Thirty-four patients with relapsing remitting MS, with ≤ 2 years of disease progression and EDSS and ≤2, and 30 healthy control subjects matched for age, sex, and educational level were recruited. Subjects performed a comprehensive neuropsychological assessment (Rao BRB). SC was assessed using the International Affective Picture System IAPS, The Eyes in the Mind Test, the Empathy Quotient, and the Faux Pas Test. The anatomical correlation of patients with deficits in social cognition was studied through brain MRI and voxel-based morphometric for which cortical reconstruction and volumetric segmentation were performed using Freesurfer processing software. Patients showed significant deficits in executive functions, verbal memory and language tests. SC assessment showed that patients presented greater difficulties in the Faux Pas Test (p = 0.023), The Mind in the Eyes Test (p = 0.014), and presented a positive bias in the interpretation of neutral images of the IAPS (P = 0.023). Furthermore, patients with CS deficits presented less cortical thickness in areas of the right supramarginal gyrus, pars opercularis, and anterior cingulum

Iron metabolism in oligodendrocytes and astrocytes: friend or foe?

Recent reports show that astrocytes (AST) are able to create a permissive environment for remyelination through their action on oligodendrocyte (OLG) precursor migration, proliferation, and differentiation. When disrupted, iron homeostasis negatively impacts OLG differentiation and impairs myelination. We demonstrate that iron deficiency (ID) affects not only OLG maturation but also AST. Using gestational iron deprivation, we studied OLG requirements for their progression to a mature myelinating state and energy metabolism in primary cultures of OLG and AST from newly born control and ID pups. In particular, oxygen consumption and extracellular acidification rates were measured using a Seahorse extracellular flux analyzer. Both ID AST and OLG exhibited decreased spare respiratory capacity, which indicates that maternal ID effectively induces mitochondrial dysfunction. Absence of glycogen granules was observed in ID AST and an increase in ROS production was detected in ID OLG. Mitochondrial fission was increased in ID AST, while fusion was prevalent in ID OLG. Electron microscopy also showed abnormal cristae in ID mitochondria in OLG as well as in AST. These findings further prove that the regulation of cell metabolism may impact cell fate decisions and maturation. An additional model of ID was developed by knocking down the divalent metal transporter 1 (DMT1), a multi-metal transporter with a primary role in iron transport and present in AST and OLG. OLG maturation was compromised in primary OPC cultures treated with conditioned medium from DMT1-silenced AST, which suggests that molecules secreted by AST may be affected.Fil: Pasquini, Juana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Rosato Siri, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Martino Adami, Pamela Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Guitart, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Marcora, Maria Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Morelli, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Correale, Jorge. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaLXVI Reunión anual de la Sociedad Argentina de Investigación Clínica; LXIX Reunión Anual de la Sociedad Argentina de Inmunología; LIII Reunión Anual de la Asociación Argentina de Farmacología Experimental y XI Reunión Anual de la Asociación Argentina de NanomedicinasArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina de InmunologíaAsociación Argentina de Farmacología ExperimentalAsociación Argentina de Nanomedicina

GAS6 signaling tempers Th17 development in patients with multiple sclerosis and helminth infection

Multiple sclerosis (MS) is a highly disabling neurodegenerative autoimmune condition in which an unbalanced immune response plays a critical role. Although the mechanisms remain poorly defined, helminth infections are known to modulate the severity and progression of chronic inflammatory diseases. The tyrosine kinase receptors TYRO3, AXL, and MERTK (TAM) have been described as inhibitors of the immune response in various inflammatory settings. We show here that patients with concurrent natural helminth infections and MS condition (HIMS) had an increased expression of the negative regulatory TAM receptors in antigen-presenting cells and their agonist GAS6 in circulating CD11bhigh and CD4+ T cells compared to patients with only MS. The Th17 subset was reduced in patients with HIMS with a subsequent downregulation of its pathogenic genetic program. Moreover, these CD4+ T cells promoted lower levels of the co-stimulatory molecules CD80, CD86, and CD40 on dendritic cells compared with CD4+ T cells from patients with MS, an effect that was GAS6-dependent. IL-10+ cells from patients with HIMS showed higher GAS6 expression levels than Th17 cells, and inhibition of phosphatidylserine/GAS6 binding led to an expansion of Th17 effector genes. The addition of GAS6 on activated CD4+ T cells from patients with MS restrains the Th17 gene expression signature. This cohort of patients with HIMS unravels a promising regulatory mechanism to dampen the Th17 inflammatory response in autoimmunity.Fil: Ortiz Wilczyñski, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Olexen, Cinthia Mariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Errasti, Andrea Emilse. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Schattner, Mirta Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Rothlin, Carla. University of Yale; Estados UnidosFil: Correale, Jorge. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Carrera Silva, Eugenio Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentin

Effects of systolic blood pressure on brain integrity in multiple sclerosis

Background: In MS patients, hypertension is associated with a delayed diagnosis and an increased risk of progression. Understanding the mechanisms of this association could potentially lead to improved prevention of disease progression. We aimed to establish whether high blood pressure contributes to white-matter injury and brain atrophy in MS. Methods: Cross-sectional study of 95 patients with RRMS. Estimates of fractional anisotropy, gray-matter volume and lesion load were obtained from 3T MRI. We used fractional anisotropy voxel-based statistics to establish the effect of blood pressure on white matter tracts. Additionally, we used voxel-based morphometry (VBM) to study the effect on gray matter integrity. Results: Only 29.5% had normal blood pressure levels, with 52.6% suffering from prehypertension and 17.9% with hypertension. Increasing systolic blood pressure was associated with damage to posterior white-matter tracts as well as greater levels of gray matter atrophy, in particular in the frontal cortex. Age-adjusted linear regression indicated that neither lesion volume (β = 0.002, 95%CI: 0.02-0.02; p = 0.85) or lesion number (β = -0.004, 95%CI: 0.03-0.02; p = 0.74) were associated with systolic blood pressure. Conclusions: Prehypertension and hypertension are frequent in MS. Increased blood pressure is related to white- and gray-matter integrity, both related to MS disability outcomes. These findings suggest attention to the control of blood pressure in MS patients.Fil: Dossi, Daiana. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Chaves, Hernán. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Heck, Evelyn Sabrina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Rodriguez Murua, Sofia. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ventrice, Fernando. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Bakshi, Rohit. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Quintana, Francisco Javier. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Correale, Jorge. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Farez, Mauricio Franco. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia. Instituto de Neurociencias - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Neurociencias; Argentin

Effects of Systolic Blood Pressure on Brain Integrity in Multiple Sclerosis

Background: In MS patients, hypertension is associated with a delayed diagnosis and an increased risk of progression. Understanding the mechanisms of this association could potentially lead to improved prevention of disease progression. We aimed to establish whether high blood pressure contributes to white-matter injury and brain atrophy in MS.Methods: Cross-sectional study of 95 patients with RRMS. Estimates of fractional anisotropy, gray-matter volume and lesion load were obtained from 3T MRI. We used fractional anisotropy voxel-based statistics to establish the effect of blood pressure on white matter tracts. Additionally, we used voxel-based morphometry (VBM) to study the effect on gray matter integrity.Results: Only 29.5% had normal blood pressure levels, with 52.6% suffering from prehypertension and 17.9% with hypertension. Increasing systolic blood pressure was associated with damage to posterior white-matter tracts as well as greater levels of gray matter atrophy, in particular in the frontal cortex. Age-adjusted linear regression indicated that neither lesion volume (β = 0.002, 95%CI: 0.02–0.02; p = 0.85) or lesion number (β = −0.004, 95%CI: 0.03–0.02; p = 0.74) were associated with systolic blood pressure.Conclusions: Prehypertension and hypertension are frequent in MS. Increased blood pressure is related to white- and gray-matter integrity, both related to MS disability outcomes. These findings suggest attention to the control of blood pressure in MS patients

Clinically relevant increases in serum neurofilament light chain and glial fibrillary acidic protein in patients with Susac syndrome

Background and purpose: Serum levels of neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) are promising neuro-axonal damage and astrocytic activation biomarkers. Susac syndrome (SS) is an increasingly recognized neurological condition and biomarkers that can help assess and monitor disease evolution are highly needed for the adequate management of these patients. sNfL and sGFAP levels were evaluated in patients with SS and their clinical relevance in the relapse and remission phase of the disease was assessed. Methods: As part of a multicentre study that enrolled patients diagnosed with SS from six international centres, sNfL and sGFAP levels were assessed in 22 SS patients (nine during a relapse and 13 in remission) and 59 age- and sex-matched healthy controls using SimoaTM assay Neurology 2-Plex B Kit. Results: Serum NfL levels were higher than those of healthy controls (p &lt; 0.001) in SS patients and in both subgroups of patients in relapse and in remission (p &lt; 0.001 for both), with significantly higher levels in relapse than in remission (p = 0.008). sNfL levels showed a negative correlation with time from the last relapse (r = -0.663; p = 0.001). sGFAP levels were slightly higher in the whole group of patients than in healthy controls (p = 0.046) and were more pronounced in relapse than in remission (p = 0.013). Conclusion: In SS patients, both sNFL and sGFAP levels increased compared with healthy controls. Both biomarkers had higher levels during clinical relapse and much lower levels in remission. sNFL was shown to be time sensitive to clinical changes and can be useful to monitor neuro-axonal damage in SS