An Exploratory Survey on the Care for Ataxic Patients in the American Continents and the Caribbean.

Little is known about access of rare disease carriers to health care. To increase this knowledge, the Pan American Hereditary Ataxia Network (PAHAN) conducted an exploratory survey about care for hereditary ataxias in American continents and the Caribbean. A questionnaire was sent to health professionals about the hereditary ataxias identified; access to care; and local teaching and research. The number of ataxics under current care per 100,000 inhabitants was subtracted from the expected overall prevalence of 6/100,000, to estimate the prevalence of uncovered ataxic patients. Local Human Development Indexes (HDI) were used to measure socio-economic factors. Twenty-six sites participated. Twelve sites had very high, 13 had high, and one site had medium HDI. Participants reported on 2239 and 602 patients with spinocerebellar ataxias and recessive forms under current care. The number of patients under current care per inhabitants varied between 0.14 and 12/100,000. The estimated prevalence of uncovered ataxic patients was inversely proportional to HDIs (rho = 0.665, p = 0.003). Access to diagnosis, pre-symptomatic tests, and rehabilitation were associated with HDIs. More and better molecular diagnostic tools, protocols and guidelines, and professional training for ataxia care were the top priorities common to all respondents. Evidence of inequalities was confirmed. Lower HDIs were associated with high potential numbers of uncovered ataxic subjects, and with lack of molecular diagnosis, pre-symptomatic testing, and rehabilitation. More and better diagnostic tools, guidelines, and professional training were priorities to all sites. PAHAN consortium might help with the last two tasks.

Peripheral Nervous System Manifestations Associated with COVID-19.

PURPOSE OF REVIEW: The present review discusses the peripheral nervous system (PNS) manifestations associated with coronavirus disease 2019 (COVID-19). RECENT FINDINGS: Nerve pain and skeletal muscle injury, Guillain-Barré syndrome, cranial polyneuritis, neuromuscular junction disorders, neuro-ophthalmological disorders, neurosensory hearing loss, and dysautonomia have been reported as PNS manifestations in patients with COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19. COVID-19 has shown syndromic complexity. Not only does SARS-CoV-2 affect the central nervous system but also it involves the PNS. The PNS involvement may be due to dysregulation of the immune system attributable to COVID-19. Here we review the broad spectrum of PNS involvement of COVID-19.

Spinocerebellar ataxia type 2 has multiple ancestral origins.

INTRODUCTION: Spinocerebellar ataxia type 2 (SCA2) is a dominant neurodegenerative disorder due to expansions of a CAG repeat tract (CAGexp) at the ATXN2 gene. Previous studies found only one ancestral haplotype worldwide, with a C allele at rs695871. This homogeneity was unexpected, given the severe anticipations related to SCA2. We aimed to describe informative ancestral haplotypes found in South American SCA2 families. METHODS: Seventy-seven SCA2 index cases were recruited from Brazil, Peru, and Uruguay; 263 normal chromosomes were used as controls. The SNPs rs9300319, rs3809274, rs695871, rs1236900 and rs593226, and the STRs D12S1329, D12S1333, D12S1672 and D12S1332, were used to reconstruct haplotypes. RESULTS: Eleven ancestral haplotypes were found in SCA2 families. The most frequent ones were A-G-C-C-C (46.7 % of families), G-C-C-C-C (24.6 %) and A-C-C-C-C (10.3 %) and their mean (sd) CAGexp were 41.68 (3.55), 40.42 (4.11) and 45.67 (9.70) (p = 0.055), respectively. In contrast, the mean (sd) CAG lengths at normal alleles grouped per haplotypes G-C-G-A-T, A-G-C-C-C and G-C-C-C-C were 22.97 (3.93), 23.85 (3.59), and 30.81 (4.27) (p < 0.001), respectively. The other SCA2 haplotypes were rare: among them, a G-C-G-A-T lineage was found, evidencing a G allele in rs695871. CONCLUSION: We identified several distinct ancestral haplotypes in SCA2 families, including an unexpected lineage with a G allele at rs695871, a variation never found in hundreds of SCA2 patients studied worldwide. SCA2 has multiple origins in South America, and more studies should be done in other regions of the world.

National stroke management plan in Uruguay: Challenges and opportunities.

Stroke accounts for 5.5% of the national Global Burden of Disease (GBD) and ~2,000 deaths per year in Uruguay. To respond to this medical emergency, the Ministry of Public Health (MPH) of Uruguay devised the National Stroke Plan (NSP). Scientific associations, universities, scholars, and patient organizations, both at the national and international levels, took part in the process, which ended with the generation of the national stroke management guidelines, including measures based on the best evidence available. This was accompanied by presidential regulatory decrees and several ordinances that set the foundations of the legal framework for their implementation as of 2020. Forty-two Stroke Ready Centers (SRC) and seven Comprehensive Stroke Centers (CSC) were strategically established and interlinked to ensure compliance with international accessibility recommendations, offering, in turn, the required training for their healthcare teams. A pre-hospital care protocol was also created for all countrywide mobile units. For NSP assessment, stroke was included as a "Care Goal (objective)" for the whole health system, providing the involved healthcare organizations with a financial incentive for compliance with the basic objectives related to the treatment of hyper acute stroke. The NSP came into force during the COVID-19 pandemic and, considering the special circumstances imposed, it made it possible to maintain hyper acute medical care and increase population access to recanalization treatment, particularly mechanical thrombectomy. The purpose of this article is to share our experience in the development of the NSP by describing some preliminary outcomes.

Fighting Against Stroke in Latin America: A Joint Effort of Medical Professional Societies and Governments.

Introduction: Stroke is one of the leading causes of death in Latin America, a region with countless gaps to be addressed to decrease its burden. In 2018, at the first Latin American Stroke Ministerial Meeting, stroke physician and healthcare manager representatives from 13 countries signed the Declaration of Gramado with the priorities to improve the region, with the commitment to implement all evidence-based strategies for stroke care. The second meeting in March 2020 reviewed the achievements in 2 years and discussed new objectives. This paper will review the 2-year advances and future plans of the Latin American alliance for stroke. Method: In March 2020, a survey based on the Declaration of Gramado items was sent to the neurologists participants of the Stroke Ministerial Meetings. The results were confirmed with representatives of the Ministries of Health and leaders from the countries at the second Latin American Stroke Ministerial Meeting. Results: In 2 years, public stroke awareness initiatives increased from 25 to 75% of countries. All countries have started programs to encourage physical activity, and there has been an increase in the number of countries that implement, at least partially, strategies to identify and treat hypertension, diabetes, and lifestyle risk factors. Programs to identify and treat dyslipidemia and atrial fibrillation still remained poor. The number of stroke centers increased from 322 to 448, all of them providing intravenous thrombolysis, with an increase in countries with stroke units. All countries have mechanical thrombectomy, but mostly restricted to a few private hospitals. Pre-hospital organization remains limited. The utilization of telemedicine has increased but is restricted to a few hospitals and is not widely available throughout the country. Patients have late, if any, access to rehabilitation after hospital discharge. Conclusion: The initiative to collaborate, exchange experiences, and unite societies and governments to improve stroke care in Latin America has yielded good results. Important advances have been made in the region in terms of increasing the number of acute stroke care services, implementing reperfusion treatments and creating programs for the detection and treatment of risk factors. We hope that this approach can reduce inequalities in stroke care in Latin America and serves as a model for other under-resourced environments.

Prodromal symptoms in epileptic patients: clinical characterization of the pre-ictal phase.

Although recent advances in seizure anticipation have been achieved with the development of several biomathematical electroencephalographic (EEG) methods, pre-ictal clinical phenomena have not been extensively investigated. The aim of the study was to thoroughly analyze premonitory or prodromal symptoms (PS) in a randomly selected sample of 100 adult epileptic patients. A semi-structured protocol was used for in-person interviews to both patients and observers. PS were found in 39% of patients, the most frequent ones being behavioral, cognitive and mood changes. Both patients with focal and generalized epilepsies reported prodromes, although they were more frequently found in the former group. PS were mostly perceived preceding complex partial and generalized tonic-clonic seizures. Prodromal symptoms were reported to have an insidious onset and their duration ranged from 30min to several hours. The potential value of prodromes in seizure anticipation would allow the use of preventive and therapeutic measures, including drugs, neurostimulation procedures and behavioral intervention.

Inter-rater and intra-rater reliability of the airway diameter measured by sonography.

INTRODUCTION: Sonography has gained a broad field of applications in current anesthetic practice. During airway management, it could have an important role, because it allows real-time measurement of anatomical aspects and a functional evaluation with high safety profile. However, assessment of the reliability and precision of these measurements is critical if sonography is used as a clinical diagnostic tool. The aim of the study was to estimate inter-rater and intra-rater reliability of the airway diameter measured by sonography in heathy volunteers. METHODS: We conducted a cross-sectional study during 2015 on healthy adult volunteers. Using sonography, transverse internal diameter of subglottic space was measured twice by two blinded sonographers. RESULTS: Agreement was classified as very good for intra-rater measurements (ICC = 0.84) and good for the inter-rater measurements (ICC = 0.71). The 95% CI of agreement limits for the intra-rater measurements were inferior to those for the inter-rater measurements. CONCLUSIONS: Ultrasound measurement is a reliable and precise method to measure the internal subglottic diameter of the airway. Ultimately, this method may provide clinicians valuable information regarding airway diameter in adults and may help to guide treatment options.

La ateromatosis aórtica aumenta el riesgo de ataque cerebrovascular isquémico / Aortic atheromatosis increases the risk of ischemic stroke

Antecedentes: el ataque cerebrovascular isquémico (ACVi) es causa de mortalidad y discapacidad importante en adultos, siendo la cardioembolia, sobre todo por fibrilación auricular (FA), una etiología importante. Se conocen otras etiologías, cardíacas y no cardíacas, que no siempre pueden definirse, refiriéndose como probables o posibles de cardioaortoembolia. El rol de alguna de ellas, como la ateromatosis aórtica (AA), continúa siendo discutido. Objetivo: analizar fuentes posibles de cardioaortoembolia en pacientes con ACVi reciente. Material y método: estudio caso-control. Se analizaron 100 sujetos con ACVi de menos de 30 días de evolución estudiados prospectivamente con ecocardiograma transesofágico (ETE), entre febrero de 2012 y marzo de 2014. Se apareó cada caso según edad, sexo, presencia de flutter/FA y ausencia de prótesis valvular cardíaca, con un control que se buscó retrospectiva y aleatoriamente entre sujetos con ETE estudiados entre 2010 y 2015 sin ACVi. Se compararon variables binarias mediante test de McNemar y las cuantitativas por test de t pareado; se realizó regresión logística múltiple para ACVi con variables clínicas y hallazgos de ETE y p < 0,1 en el análisis univariado. Se consideró significativo p < 0,05. Variables cuantitativas se expresan en media y desvío estándar (DE) y nominales en valor absoluto y porcentaje, índice de probabilidad (OR) en su valor e intervalo de confianza (IC) 95%. Resultados: se formaron finalmente 76 pares caso-control. Edad casos: 64,3±1,4 y control 64,9±1,3 años (p=0,19); 39 mujeres (51,3%) y 15 sujetos (19,7%) con flutter/FA en cada grupo (p=1). No hubo diferencias significativas según factores de riesgo cardiovascular (FRCV) globales (p=0,06) ni alcoholismo (p=0,80); se encontraron diferencias significativas en la prevalencia de dislipemia (p=0,03) e hipertensión arterial (HTA) (p <0,05). Las indicaciones principales del ETE en los controles fueron: previo a cardioversión eléctrica de FA, sospecha de endocarditis, y valoración de valvulopatía mitral. La ateromatosis aórtica proximal y compleja (AAPC) (p=0,002, OR 5,5, IC95% 1,9-15,9) y la AA en forma global (p=0,001, OR 4,1, IC95% 1,8-9,3), además de la dislipemia (p=0,02, OR 2,8 IC95% 1,2-6,4), se asociaron significativamente con la presencia de ACVi en el análisis multivariado. Conclusión: la AA aumenta significativamente las chances de ACVi y las quintuplica cuando es proximal y compleja. La dislipemia se asoció a ACVi.

Background: Ischemic stroke is an important cause of death and disability in adults; cardio-embolism especially due to atrial fibrillation is a major cause of cerebrovascular attack. Other cardiac and non-cardiac causes are known but it is not always possible to establish etiology. There are probable and possible sources of cardio-embolism. The causal role of some possible etiologies as aortic atheromatosis remains discussed. Objective: To analyze possible sources of cardio-aortoembolism in acute ischemic cerebrovascular attack patients. Method: Study Design: Case-control. 100 subjects with ischemic cerebrovascular attack and less than 30 days from diagnosis were prospectively studied with transesophageal echocardiography between February 2012 and March 2014. They were matched by age, sex and presence of flutter / atrial fibrillation and absence of cardiac valvar prosthesis. Each control was recruited randomly and looking back among subjects without history of cerebrovascular disease, with transesophageal echocardiography previously studied between 2010 and 2015. Binary variables were compared using the McNemar test and quantitative by paired test of t, multiple logistic regression was performed with ischemic stroke as outcome, taking in consideration clinical variables and echocardiographic findings. Quantitative variables are expressed as media and standard deviation and nominal as its percentage value, association value as odds ratio (OR), value and 95% confident interval (CI 95%) Results: 76 case-control pairs were finally included. Cases´ age: 64.3 ± 1.4 years and controls´ 64.9 ± 1.3 (p=0.19). 39 women (51.3%) and 15 (19.7% subjects) with flutter / atrial fibrillation in each group (p=1). No significant differences were found about global cardiovascular risk factors (p=0.06) or alcoholism (p=0,80); significant differences in the prevalence of dyslipidemia and hypertension (p=0.03; 0.05) were found. Main reasons for transesophageal echocardiography in controls were: for cardioversion of atrial fibrillation, suspected endocarditis and mitral valve rating. Proximal and complex aortic atheromatosis (p=0,002, OR 5,5, IC95% 1,9-15,9), and aortic atheromatosis in general (p=0,001, OR 4,1, IC95% 1,8-9,3) and dyslipidemia (p=0,02, OR 2,8 IC95% 1,2-6,4), were significantly associated with the presence of ischemic cerebrovascular attack in multivariate analysis. Conclusion: Aortic atheromatosis significantly increases the risk of ischemic stroke, five times when proximal and complex. Dyslipidemia is associated with ischemic cerebrovascular attack.

Relevancia clínica del ecocardiograma transesofágico en pacientes con ataque cerebrovascular isquémico: Estudio observacional, analítico / Clinical relevance of transesophageal echocardiography in patients with ischemic stroke: Observational, analytical study

Antecedentes: la búsqueda de cardioaortoembolia es prioritaria en pacientes con ataque cerebrovascular isquémico (ACVi). El ecocardiograma transesofágico (ETE) tiene mayor sensibilidad que el transtorácico (ETT) para detectar fuentes de cardioaortoembolia. Sin embargo, su indicación y relevancia no están totalmente definidas en la valoración inicial de estos pacientes. Objetivo: explorar la relevancia clínica de la realización sistemática de ETE en pacientes con ACVi. Método: estudio de corte transversal en el que 100 pacientes consecutivos con diagnóstico de ACVi, que otorgaron consentimiento, fueron incluidos prospectivamente entre febrero de 2012 y marzo de 2014. Dos cardiólogos independientes, ciegos entre sí, realizaron ETT y ETE durante el ingreso hospitalario de cada paciente. Otro cardiólogo, según la historia clínica, electrocardiograma (ECG) y ETT definió riesgo de embolia y tratamiento siguiendo pautas habituales. Según el resultado del ETE, se respondió: ¿Cambió la estimación de riesgo embólico? ¿Cambió la indicación terapéutica? Se consideró clínicamente relevante un número de ETE necesario (NEN) £ 10 y £ 15 por cada respuesta afirmativa, respectivamente. Secundariamente se estudió la capacidad diagnóstica del ETT versus ETE para cardioaortoembolia. Resultado: cincuenta hombres (50%); edad 64 ± 12 años, 18 con fibrilación auricular y 94 con infarto cerebral. NEN para cambiar una estimación de riesgo 2,85, IC 95% (2,3-3,9) y para cambiar un tratamiento 10, IC 95% (6,3-24,3). El ETT mostró una sensibilidad para fuente de cardioaortoembolia de 43,9% (IC 95% 31,0-56,7) y una especificidad de 81,4% (IC 95% 69,8-93,0) comparado con ETE tomado como gold standard. Conclusión: el ETE aporta información relevante para estimación de riesgo embólico y definición terapéutica en pacientes con ACVi, esto último sin significación estadística.

Background: search of cardiac and aortic source of emboli is crucial in managing acute cerebrovascular diseases (ACVD). Systematic use of transesophageal echocardiography (TEE) has not yet been defined, even though TEE is much more sensitive than transthoracic echocardiography (TTE). Purpose: to explore clinical relevance of systematic use of TEE in ACVD. Method: consecutive patients diagnosed with a new ischemic stroke or transient ischemic attack (TIA), have been assessed in-hospital between 2/2012 and 3/2014. Two independent cardiologists blinded to each other performed TTE and TEE. Another cardiologist, considering clinical history and TTE, determined embolic risk and established treatment according to clinical guidelines. Considering TEE result, these questions were answered: ¿Did TEE result change risk assessment? ¿Did TEE result change treatment indication (new drug indication, new goal for an old one or new intervention)?. It was considered as clinically relevant a needed number of TEE (NNT) £10 for risk assessment and £ 15 for treatment under each affirmative answer. Results: one hundred patients (50 men, age 64±12 years) were recruited; 18 patients with atrial fibrillation; 94 patients with stroke. NNT: 2,85 IC 95%(2,3- 3,9), to change one assessment and 10 IC 95%(6,3-24,3) to change one treatment. Diagnostic value of TTE vs TEE (as gold standard) was: TTE sensibility 43,9% (31,0-56,7) and specificity 81,4% (69,8-93,0). Conclusions: TEE gives clinically relevant information to change risk embolic assessment in TIA/stroke patients, but this information was not statistical significant in order to define treatment changes.

Unidad de ACV en el Hospital de Clínicas: comportamiento clínico-epidemiológico de los pacientes con ACV (2007-2012) / Stroke Unit at the Hospital de Clínicas: clinical-epidemiological behavior in patients with stroke (2007-2012)

Introducción: El ataque cerebrovascular (ACV) es una importante causa de mortalidad, discapacidad y demencia en el mundo y en nuestro país. Provoca un gran impacto económico ya sea por gastos directos o indirectos. Objetivos: Describir aspectos clínicos, factores de riesgo e indicadores que permiten un adecuado manejo del ACV en su tratamiento agudo. Material y Métodos: Se realizó un estudio descriptivo y prospectivo de los ACV ingresados en el Hospital de Clínicas, entre 2007 y 2012 aplicando un protocolo con escalas clínicas, etiopatogénicas y funcionales, con test estadísticos adecuados. Resultados: Se protocolizaron 784 pacientes: 75% infartos, 16% hemorragias y 9% AIT. La HTA fue el factor de riesgo más frecuente. Un tercio llegó a puerta antes de las 4,5 h. En infartos y AIT se disminuyeron los días de internación y se mejoró la funcionalidad a 6 meses. Conclusiones: La formación de equipos entrenados en el diagnóstico y tratamiento del ACV disminuyeron el tiempo de internación y mejoraron la funcionalidad de estos pacientes.

Introduction: The cerebrospinal fluid (CSF) fistula is defined as the abnormal leak of fluid from the skull to outside the body through an osteomeningeal gap, which allows the passage of organisms to the intra-cranial space, with the risk of infection, potentially life-threatening. Divided as traumatic and non-traumatic, the condition is relatively common, and poses great challenges to neurosurgeons. Objective: to present the first case of post-traumatic CSF fistula in Uruguay, assessed with cistern MRI with diagnostic purposes. Case report: the case described is that of a patient that received treatment at the University Hospital (Hospital de Clínicas). The case is used to illustrate the condition and review the latest controversial issues involved in the algorithms for the diagnosis and therapy of the condition. Discussion: the main controversial issues found included the following: when to start prophylactic antibiotic (ATB) therapy following diagnosis; imaging tests requested for diagnosis, and type of therapy prescribed. Conclusions: The review of literature leads us to conclude that a correct diagnosis requires the routine use of CT and MRI; if doubts persist, cistern MRI, endoscopy, or cistern CT are indicated. With regards the therapeutic algorithm, we conclude that therapy should be conservative, applying medical therapy for two to four weeks; surgery will be prescribed if the fistula persists after that. Antibiotic therapy is an option and not a recommendation.

Ataque cerebrovascular isquémico en Uruguay: comunicación de los primeros 34 casos trombolizados en el Hospital de Clínicas / Ischemic stroke in Uruguay. First 34 cases of thrombolized patients at the Clinicas Hospital

Introducción: el ataque cerebrovascular (ACV) constituye un problema de salud en Uruguay y en el mundo. Se ha comprobado que la trombolisis intravenosa disminuye la morbimortalidad y las secuelas en los pacientes con ACV isquémicos agudos (nivel de evidencia IA). Objetivos: analizar los casos de ACV isquémico trombolizados en el Hospital de Clínicas y valorar la utilidad de un score de predicción de sangrado intracraneano sintomático en esta población. Material y método: estudio descriptivo, observacional y prospectivo. Población: pacientes trombolizados en el Hospital de Clínicas en el período 2010-2013. Se aplicó score predictivo de hemorragia sintomática a toda la población de trombolizados. Tests estadísticos: test de chi cuadrado, test de student, test de Wilcoxon, se consideraron diferencias estadísticamente significativas aquellas con una p < 0,05. Resultados: treinta y cuatro pacientes trombolizados, promedio de edad 67 años, mayoría mujeres, alto porcentaje de ACV graves, National Institute of Health Stroke Scale (NIHSS) promedio al ingreso: 11, con mejoría estadísticamente significativa al alta. Etiología principal: cardioembolia. Tiempo síntoma aguja promedio: 170 minutos. Hemorragia intracraneana: ocho pacientes (23,5%), fallecieron cuatro de ellos. El puntaje del score de sangrado no predijo el sangrado intracraneano. Conclusiones: en el Hospital de Clínicas, desde la inauguración de la Unidad de ACV, el porcentaje de infartos cerebrales trombolizados ha ido en aumento, siendo actualmente comparable a cifras internacionales. El tiempo síntoma-aguja es menor que en otros estudios. La trombolisis generó un beneficio estadísticamente significativo en la escala de NIHSS. El porcentaje de sangrados fue similar al descrito en la literatura...

Tromboprofilaxis y anticoagulación luego del ataque cerebrovascular hemorrágico / Thromboprophylaxis and anticoagulation after hemorrhagic stroke

El ataque cerebrovascular hemorrágico o hemorragia cerebral no traumática es una importante causa de mortalidad y morbilidad a nivel mundial y constituye el efecto adverso más temido de la terapia anticoagulante. Cuando ésta ocurre es significativamente más letal que otras hemorragias constituyendo el 90% de las muertes ocasionadas por sangrados en pacientes que reciben warfarina. La enfermedad tromboembólica es una complicación frecuente en los pacientes que han sufrido un ataque cerebrovascular lo que determina que la profilaxis y tratamiento de eventos tromboembólicos versus el riesgo de recurrencia de sangrado intracraneano constituya un verdadero desafio clínico-terapéutico. El objetivo de esta revisión es analizar la importancia de la enfermedad tromboembólica en los pacientes con hemorragia cerebral, la tromboprofilaxis y el manejo de los pacientes tratados con anticoagulantes orales y la oportunidad de reinicio de los mismos luego de una hemorragia cerebral reciente.

ABSTRACT: Arch Med Interna 2012 - 34(3):80-87 Hemorrhagic stroke or non traumatic cerebral hemorrhage is a significant cause of morbi-mortality globally, and it is the most dreaded adverse effect of anticoagulant therapy. When it does occur, it is significantly more lethal than other hemorrhages, and it accounts for 90% of the deaths that result from bleeding in patients receiving warfarin. Thromboembolic disease is a frequent complication in patients with stroke; therefore, balancing the prophylaxis and therapy of thromboembolic events with the risk of recurrence of intracranial bleeding becomes a true clinical and therapeutic challenge. The objective of this review is to discuss the importance of thromboembolic disease in patients presenting with cerebral hemorrhage, thromboprophylaxis and the management of the patients treated with oral anticoagulants, as well as the timing for resuming the administration of such agents after a recent cerebral hemorrhage.