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

Rivaroxaban or aspirin for patent foramen ovale and embolic stroke of undetermined source: a prespecified subgroup analysis from the NAVIGATE ESUS trial

Background: Patent foramen ovale (PFO) is a contributor to embolic stroke of undetermined source (ESUS). Subgroup analyses from previous studies suggest that anticoagulation could reduce recurrent stroke compared with antiplatelet therapy. We hypothesised that anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, would reduce the risk of recurrent ischaemic stroke compared with aspirin among patients with PFO enrolled in the NAVIGATE ESUS trial. Methods: NAVIGATE ESUS was a double-blinded, randomised, phase 3 trial done at 459 centres in 31 countries that assessed the efficacy and safety of rivaroxaban versus aspirin for secondary stroke prevention in patients with ESUS. For this prespecified subgroup analysis, cohorts with and without PFO were defined on the basis of transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE). The primary efficacy outcome was time to recurrent ischaemic stroke between treatment groups. The primary safety outcome was major bleeding, according to the criteria of the International Society of Thrombosis and Haemostasis. The primary analyses were based on the intention-to-treat population. Additionally, we did a systematic review and random-effects meta-analysis of studies in which patients with cryptogenic stroke and PFO were randomly assigned to receive anticoagulant or antiplatelet therapy. Findings: Between Dec 23, 2014, and Sept 20, 2017, 7213 participants were enrolled and assigned to receive rivaroxaban (n=3609) or aspirin (n=3604). Patients were followed up for a mean of 11 months because of early trial termination. PFO was reported as present in 534 (7·4%) patients on the basis of either TTE or TOE. Patients with PFO assigned to receive aspirin had a recurrent ischaemic stroke rate of 4·8 events per 100 person-years compared with 2·6 events per 100 person-years in those treated with rivaroxaban. Among patients with known PFO, there was insufficient evidence to support a difference in risk of recurrent ischaemic stroke between rivaroxaban and aspirin (hazard ratio [HR] 0·54; 95% CI 0·22–1·36), and the risk was similar for those without known PFO (1·06; 0·84–1·33; pinteraction=0·18). The risks of major bleeding with rivaroxaban versus aspirin were similar in patients with PFO detected (HR 2·05; 95% CI 0·51–8·18) and in those without PFO detected (HR 2·82; 95% CI 1·69–4·70; pinteraction=0·68). The random-effects meta-analysis combined data from NAVIGATE ESUS with data from two previous trials (PICSS and CLOSE) and yielded a summary odds ratio of 0·48 (95% CI 0·24–0·96; p=0·04) for ischaemic stroke in favour of anticoagulation, without evidence of heterogeneity. Interpretation: Among patients with ESUS who have PFO, anticoagulation might reduce the risk of recurrent stroke by about half, although substantial imprecision remains. Dedicated trials of anticoagulation versus antiplatelet therapy or PFO closure, or both, are warranted. Funding: Bayer and Janssen

Embolic strokes of undetermined source: prevalence and patient features in the ESUS Global Registry

Background: Recent evidence supports that most non-lacunar cryptogenic strokes are embolic. Accordingly, these strokes have been designated as embolic strokes of undetermined source (ESUS). Aims: We undertook an international survey to characterize the frequency and clinical features of ESUS patients across global regions. Methods: Consecutive patients hospitalized for ischemic stroke were retrospectively surveyed from 19 stroke research centers in 19 different countries to collect patients meeting criteria for ESUS. Results: Of 2144 patients with recent ischemic stroke, 351 (16%, 95% CI 15% to 18%) met ESUS criteria, similar across global regions (range 16% to 21%), and an additional 308 (14%) patients had incomplete evaluation required for ESUS diagnosis. The mean age of ESUS patients (62 years; SD = 15) was significantly lower than the 1793 non-ESUS ischemic stroke patients (68 years, p ≤ 0.001). Excluding patients with atrial fibrillation (n = 590, mean age = 75 years), the mean age of the remaining 1203 non-ESUS ischemic stroke patients was 64 years (p = 0.02 vs. ESUS patients). Among ESUS patients, hypertension, diabetes, and prior stroke were present in 64%, 25%, and 17%, respectively. Median NIHSS score was 4 (interquartile range 2–8). At discharge, 90% of ESUS patients received antiplatelet therapy and 7% received anticoagulation. Conclusions: This cross-sectional global sample of patients with recent ischemic stroke shows that one-sixth met criteria for ESUS, with additional ESUS patients likely among those with incomplete diagnostic investigation. ESUS patients were relatively young with mild strokes. Antiplatelet therapy was the standard antithrombotic therapy for secondary stroke prevention in all global regions

Rivaroxaban or aspirin for patent foramen ovale and embolic stroke of undetermined source: a prespecified subgroup analysis from the NAVIGATE ESUS trial

Background: Patent foramen ovale (PFO) is a contributor to embolic stroke of undetermined source (ESUS). Subgroup analyses from previous studies suggest that anticoagulation could reduce recurrent stroke compared with antiplatelet therapy. We hypothesised that anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, would reduce the risk of recurrent ischaemic stroke compared with aspirin among patients with PFO enrolled in the NAVIGATE ESUS trial. Methods: NAVIGATE ESUS was a double-blinded, randomised, phase 3 trial done at 459 centres in 31 countries that assessed the efficacy and safety of rivaroxaban versus aspirin for secondary stroke prevention in patients with ESUS. For this prespecified subgroup analysis, cohorts with and without PFO were defined on the basis of transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE). The primary efficacy outcome was time to recurrent ischaemic stroke between treatment groups. The primary safety outcome was major bleeding, according to the criteria of the International Society of Thrombosis and Haemostasis. The primary analyses were based on the intention-to-treat population. Additionally, we did a systematic review and random-effects meta-analysis of studies in which patients with cryptogenic stroke and PFO were randomly assigned to receive anticoagulant or antiplatelet therapy. Findings: Between Dec 23, 2014, and Sept 20, 2017, 7213 participants were enrolled and assigned to receive rivaroxaban (n=3609) or aspirin (n=3604). Patients were followed up for a mean of 11 months because of early trial termination. PFO was reported as present in 534 (7·4%) patients on the basis of either TTE or TOE. Patients with PFO assigned to receive aspirin had a recurrent ischaemic stroke rate of 4·8 events per 100 person-years compared with 2·6 events per 100 person-years in those treated with rivaroxaban. Among patients with known PFO, there was insufficient evidence to support a difference in risk of recurrent ischaemic stroke between rivaroxaban and aspirin (hazard ratio [HR] 0·54; 95% CI 0·22–1·36), and the risk was similar for those without known PFO (1·06; 0·84–1·33; pinteraction=0·18). The risks of major bleeding with rivaroxaban versus aspirin were similar in patients with PFO detected (HR 2·05; 95% CI 0·51–8·18) and in those without PFO detected (HR 2·82; 95% CI 1·69–4·70; pinteraction=0·68). The random-effects meta-analysis combined data from NAVIGATE ESUS with data from two previous trials (PICSS and CLOSE) and yielded a summary odds ratio of 0·48 (95% CI 0·24–0·96; p=0·04) for ischaemic stroke in favour of anticoagulation, without evidence of heterogeneity. Interpretation: Among patients with ESUS who have PFO, anticoagulation might reduce the risk of recurrent stroke by about half, although substantial imprecision remains. Dedicated trials of anticoagulation versus antiplatelet therapy or PFO closure, or both, are warranted. Funding: Bayer and Janssen

Multidisciplinary rehabilitation for adult patients with stroke

Se estima que dos tercios de las personas que han sufrido un accidente cerebrovascular (ACV) tienen secuelas que condicionan su calidad de vida. La rehabilitación del ACV es un proceso complejo, que requiere de un equipo multidisciplinario de profesionales especializados (médicos, kinesiólogos, enfermeros, terapistas ocupacionales, fonoaudiólogos, neuropsicólogos y nutricionistas). Actualmente, las prácticas realizadas en rehabilitación son consecuencia de la combinación de evidencia y consenso, siendo la mayoría aportadas a través de guías internacionales de rehabilitación en ACV. El objetivo de esta revisión es ajustar las recomendaciones internacionales sobre rehabilitación a lo aplicado a la práctica diaria, a fin de unificar criterios en las recomendaciones y reducir la variabilidad de las prácticas empleadas. En este trabajo, se realizó una revisión de la literatura sobre las guías de rehabilitación en ACV realizadas en los últimos 10 años y cada apartado fue supervisado por distintos profesionales especializados en dichas áreas. Se analizaron los tiempos y organización necesaria para desarrollarla, las recomendaciones para la rehabilitación motora, cognitiva y visual, el tratamiento de la disfagia y nutrición, de las comorbilidades (trombosis venosa, úlceras cutáneas, dolor, trastornos psiquiátricos, osteoporosis) y las tareas necesarias para favorecer el retorno a las actividades de la vida diaria.It is estimated that two thirds of people who have suffered a stroke have sequels that condition their quality of life. The rehabilitation of the stroke is a complex process, which requires the multidisciplinary approach of specialized professionals (doctors, kinesiologists, nurses, occupational therapists, phonoaudiologists, neuropsychologists and nutritionists). Currently, the practices carried out are a consequence of the combination of evidence and consensus, most of them through international stroke rehabilitation guides. The objective of this review is to adjust the international recommendations on stroke rehabilitation to what is applied to daily practice, in order to unify the criteria of the recommendations and to reduce the variability of the practices carried out. This work is a review of the literature on stroke rehabilitation guides developed in the last 10 years. Each section was supervised by different professionals specialized in these areas. We analyze the time and organization necessary to develop rehabilitation, recommendations for motor, cognitive and visual rehabilitation, the management of dysphagia and nutrition, the approach of comorbidities (venous thrombosis, skin ulcers, pain, psychiatric disorders and osteoporosis) and the necessary tasks to favor the return to the activities of daily life.Fil: Alessandro, Lucas. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Olmos, Lisandro. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Bonamico, Lucas. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Muzio, Diana M.. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Ahumada, Martina H.. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Russo, María Julieta. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Allegri, Ricardo Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Gianella, Matias G.. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Campora, Horacio. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Delorme, Ricardo. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Vescovo, Maria Esther. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Lado, Vanina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Mastroberti, Liliana R.. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Butus, Ayelen. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Galluzzi, Hugo D.. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Décima, Graciela. 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; Argentin

Rivaroxaban for secondary stroke prevention in patients with embolic strokes of undetermined source : Design of the NAVIGATE ESUS randomized trial

Peer reviewe

Rivaroxaban versus aspirin for prevention of covert brain infarcts in patients with embolic stroke of undetermined source: NAVIGATE ESUS MRI substudy

Background: Covert brain infarcts are associated with important neurological morbidity. Their incidence in patients with embolic stroke of undetermined source (ESUS) is unknown. Aims: To assess the incidence of covert brain infarcts and cerebral microbleeds using MRI in a prospective substudy of the NAVIGATE ESUS randomized trial and to evaluate the effects of antithrombotic therapies. Methods: At 87 sites in 15 countries, substudy participants were randomly assigned to receive rivaroxaban 15 mg daily or aspirin 100 mg daily and underwent brain MRI near randomization and after study termination. The primary outcome was incident brain infarct (clinical ischemic stroke or covert brain infarct). Brain infarcts and microbleeds were ascertained centrally by readers unaware of treatment. Treatment effects were estimated using logistic regression. Results: Among the 718 substudy participants with interpretable, paired MRIs, the mean age was 67 years and 61% were men with a median of 52 days between the qualifying ischemic stroke and randomization and a median of seven days between randomization and baseline MRI. During the median (IQR) 11 (12) month interval between scans, clinical ischemic strokes occurred in 27 (4%) participants, while 60 (9%) of the remaining participants had an incident covert brain infarct detected by MRI. Assignment to rivaroxaban was not associated with reduction in the incidence of brain infarct (OR 0.77, 95% CI 0.49, 1.2) or of covert brain infarct among those without clinical stroke (OR 0.85, 95% CI 0.50, 1.4). New microbleeds were observed in 7% and did not differ among those assigned rivaroxaban vs. aspirin (HR 0.95, 95% CI 0.52–1.7). Conclusions: Incident covert brain infarcts occurred in twice as many ESUS patients as a clinical ischemic stroke. Treatment with rivaroxaban compared with aspirin did not significantly reduce the incidence of covert brain infarcts or increase the incidence of microbleeds, but the confidence intervals for treatment effects were wide. Registration: https://www.clinicaltrials.gov. Unique identifier: NCT 02313909

Deterioro cognitivo reversible y parkinsonismo con leucoencefalopatía por fístula arteriovenosa dural craneal

Parkinsonism and rapid cognitive impairment may have many causes, but only a few have specific treatment. Cranial dural arteriovenous fistula (DAVF) represents 10%-15% of intracranial arteriovenous malformations. Clinical manifestations depend on location and venous drainage. It is common the presence of pulsatile tinnitus, bruits and headache or headache and papilledema. Progressive cognitive decline is an unusual presentation due to bilateral thalamic edema or cortical venous hypertension. Endovascular or surgical treatment can reverse disease symptoms. We present a 74-year old man with rapidly progressive cognitive impairment and parkinsonism and a subsequent diagnosis of dural arteriovenous fistula (DAVF). Brain MRI revealed diffuse leukoencephalopathy probably attributable to elevated venous pressure. He was treated with partial embolization with Onix and left transverse sinus angioplasty. Following the procedure, there was a substantial reduction of venous pressure signs and remarkable clinical and imaging improvement, persisting at two years follow-up. This case represents an unusual presentation of DAVF. It is important to suspect the diagnosis of DAVF in cases with rapidly evolving cognitive impairment, parkinsonism and leukoencephalopathy as it can be reversible with early treatment.El parkinsonismo y deterioro cognitivo rápidamente evolutivo puede tener múltiples causas, pero solo unas pocas cuentan con un tratamiento específico. Las fístulas arteriovenosas durales (FAVD) representan el 10%-15% de las malformaciones vasculares intracraneales. Las manifestaciones clínicas dependen de la locación de la misma y del drenaje venoso. La presentación más frecuente es tinnitus, soplos y cefalea o cefalea y papiledema. El deterioro cognitivo es una presentación inusual y puede ser debido a edema bitalámico o hipertensión venosa cortical. El tratamiento endovascular o neuroquirúrgico puede revertir los síntomas. Presentamos un caso de un paciente de sexo masculino de 74 años de edad, con un cuadro de deterioro cognitivo rápidamente evolutivo y parkinsonismo con un diagnóstico subsecuente de FAVD. La resonancia de cerebro mostró leucoencefalopatía probablemente atribuible a elevación de la presión venosa intracerebral. El paciente fue tratado con embolización parcial con Onix y angioplastía del seno venoso transverso izquierdo. Posterior al procedimiento se observó una marcada mejoría clínica e imagenológica, siendo persistente a los dos años del seguimiento. Este caso representa una presentación atípica de FAVD. Es importante sospechar este diagnóstico en casos de deterioro cognitivo rápidamente evolutivo con parkinsonismo y leucoencefalopatía ya que puede ser reversible con un tratamiento temprano