A task force for diagnosis and treatment of people with Alzheimer's disease in Latin America.

Alzheimer's disease (AD) represents a substantial burden to patients, their caregivers, health systems, and society in Latin America and the Caribbean (LAC). This impact is exacerbated by limited access to diagnosis, specialized care, and therapies for AD within and among nations. The region has varied geographic, ethnic, cultural, and economic conditions, which create unique challenges to AD diagnosis and management. To address these issues, the Americas Health Foundation convened a panel of eight neurologists, geriatricians, and psychiatrists from Argentina, Brazil, Colombia, Ecuador, Guatemala, Mexico, and Peru who are experts in AD for a three-day virtual meeting to discuss best practices for AD diagnosis and treatment in LAC and create a manuscript offering recommendations to address identified barriers. In LAC, several barriers hamper diagnosing and treating people with dementia. These barriers include access to healthcare, fragmented healthcare systems, limited research funding, unstandardized diagnosis and treatment, genetic heterogeneity, and varying social determinants of health. Additional training for physicians and other healthcare workers at the primary care level, region-specific or adequately adapted cognitive tests, increased public healthcare insurance coverage of testing and treatment, and dedicated search strategies to detect populations with gene variants associated with AD are among the recommendations to improve the landscape of AD.

Transient Global Amnesia Recurrence: Prevalence and Risk Factor Meta-analysis.

Background and Objectives: Transient global amnesia (TGA) is an acute amnestic disorder with unclear pathophysiology. Although considered a benign phenomenon, the possibility of a recurrence is a major concern for the patient. Our objective is to identify the prevalence and risk factors of relapse to help clinicians counsel patients about it. Methods: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidance, we screened 1,658 studies from MEDLINE, Lilacs, and Embase databases, published from 1985 to April 2021, in English or Spanish. We included 36 observational case-control and cohort studies that included patients with TGA according to the Caplan or Hodges and Warlow diagnostic criteria. We performed a meta-analysis with a random effect model for proportions and calculation of odds ratio (OR) for identified risk factors. Methodological quality was assessed according to the Newcastle-Ottawa scale. Results: We identified 4,514 TGA cases and 544 recurrence events (12.73%). A follow-up had no effect on its variance. We identified a statistically significant association between recurrence and sexual activity as a trigger, a personal history or current state of migraine and depression (OR 1,481 95% CI [1.0341-2.1222] p = 0.04; OR = 2.0795 95% CI [1.3892-3.1128] p = 0.003; and OR = 4.4871 95% CI [1.890-10.651] p = 0.0288, respectively). Discussion: The analysis showed that approximately 1 of 8 participants may experience recurrence, with an increased risk in the case of a history or current state of migraine, depression, or sexual intercourse before the event. A personal history of migraine and depression was associated with 2 and 4 times risk, respectively.

Working Group Recommendations for the Practice of Teleneuropsychology in Latin America.

OBJECTIVE: Teleneuropsychology (teleNP) could potentially expand access to services for patients who are confined, have limited personal access to healthcare, or live in remote areas. The emergence of the COVID-19 pandemic has significantly increased the use of teleNP for cognitive assessments. The main objective of these recommendations is to identify which procedures can be potentially best adapted to the practice of teleNP in Latin America, and thereby facilitate professional decision-making in the region. METHOD: Steps taken to develop these recommendations included (1) formation of an international working group with representatives from 12 Latin American countries; (2) assessment of rationale, scope, and objectives; (3) formulation of clinical questions; (4) evidence search and selection; (5) evaluation of existing evidence and summary; and (6) formulation of recommendations. Levels of evidence were graded following the Oxford Centre for Evidence-Based Medicine system. Databases examined included PubMed, WHO-IRIS, WHO and PAHO-IRIS, Índice Bibliográfico Español en Ciencias de la Salud (IBCS), and LILACS. RESULTS: Working group members reviewed 18,400 titles and 422 abstracts and identified 19 articles meeting the criteria for level of evidence, categorization, and elaboration of recommendations. The vast majority of the literature included teleNP tests in the English language. The working group proposed a series of recommendations that can be potentially best adapted to the practice of teleNP in Latin America. CONCLUSIONS: There is currently sufficient evidence to support the use of videoconferencing technology for remote neuropsychological assessments. These recommendations will likely contribute to the advancement of teleNP research and practice in the region.

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.

Transient global amnesia: clinical features and prognostic factors suggesting recurrence.

OBJECTIVE: The risk of recurrence of new amnesia events in patients having previously experienced transient global amnesia (TGA) ranges between 2.9-23.8%. Our objective was to search for recurrence predictors in TGA patients. METHODS: Retrospective analysis to identify recurrence predictors in a cohort of 203 TGA patients from a single center in Buenos Aires, Argentina, diagnosed between January 2011 and March 2017 Clinical features and complementary studies (laboratory results, jugular vein Doppler ultrasound and brain MRI) were analyzed. Comparison between patients with recurrent versus single episode TGA was performed, applying a multivariate logistic regression model. RESULTS: Mean age at presentation was 65 years (20-84); 52% were female. Median time elapsed between symptom onset and ER visit was two hours, with the average episode duration lasting four hours. Mean follow-up was 22 months. Sixty-six percent of patients referred to an identifiable trigger. Jugular reflux was present in 66% of patients; and 22% showed images with hippocampus restriction on diffusion-weighted MRI. Eight percent of patients had TGA recurrence. Patients with recurrent TGA had a more frequent history of migraine than patients without recurrence (37.5% vs. 14%; p = 0.03). None of the other clinical characteristics and complementary studies were predictors of increased risk of recurrence. CONCLUSIONS: Patients with migraine may have a higher risk of recurrent TGA. None of the other clinical characteristics evaluated allowed us to predict an increased risk of recurrence. Although the complementary studies allowed us to guide the diagnosis, they did not appear to have a significant impact on the prediction of recurrence risk.

Transient global amnesia: clinical features and prognostic factors suggesting recurrence / Amnesia global transitoria: características clínicas y factores pronósticos sugestivos de recurrencia

ABSTRACT The risk of recurrence of new amnesia events in patients having previously experienced transient global amnesia (TGA) ranges between 2.9-23.8%. Objective: Our objective was to search for recurrence predictors in TGA patients. Methods: Retrospective analysis to identify recurrence predictors in a cohort of 203 TGA patients from a single center in Buenos Aires, Argentina, diagnosed between January 2011 and March 2017 Clinical features and complementary studies (laboratory results, jugular vein Doppler ultrasound and brain MRI) were analyzed. Comparison between patients with recurrent versus single episode TGA was performed, applying a multivariate logistic regression model. Results: Mean age at presentation was 65 years (20-84); 52% were female. Median time elapsed between symptom onset and ER visit was two hours, with the average episode duration lasting four hours. Mean follow-up was 22 months. Sixty-six percent of patients referred to an identifiable trigger. Jugular reflux was present in 66% of patients; and 22% showed images with hippocampus restriction on diffusion-weighted MRI. Eight percent of patients had TGA recurrence. Patients with recurrent TGA had a more frequent history of migraine than patients without recurrence (37.5% vs. 14%; p = 0.03). None of the other clinical characteristics and complementary studies were predictors of increased risk of recurrence. Conclusions: Patients with migraine may have a higher risk of recurrent TGA. None of the other clinical characteristics evaluated allowed us to predict an increased risk of recurrence. Although the complementary studies allowed us to guide the diagnosis, they did not appear to have a significant impact on the prediction of recurrence risk.

RESUMEN El riesgo de recurrencia de nuevos eventos de amnesia en pacientes que han experimentado previamente Amnesia Global Transitoria (AGT) oscila entre el 2.9-23.8%. Objetivo: Nuestro objetivo fue buscar predictores de recurrencia en pacientes con AGT. Métodos: Análisis retrospectivo de una cohorte de 203 pacientes con AGT de un único centro en Buenos Aires, Argentina, diagnosticados entre enero-2011 y marzo-2017 Se analizaron las características clínicas y los estudios complementarios (laboratorio, Doppler de vena yugular y RM encéfalo). Se comparó el grupo de AGT recurrente versus episodio único, aplicando un modelo de regresión logística multivariada. Resultados: la edad promedio de presentación fue de 65 años (20-84); 52% mujeres. La mediana del tiempo transcurrido entre el inicio de los síntomas y la visita a la sala de emergencia fue de 2 horas, con una duración promedio del episodio de 4 horas. El seguimiento medio fue de 22 meses. 66% de los pacientes tuvieron un desencadenante identificable. El reflujo yugular estuvo presente en el 66% de los pacientes y el 22% mostró imágenes restrictivas en DWI a nivel hipocampal. 8% de los pacientes presentaron recurrencia. Los pacientes con AGT recurrente tuvieron un historial de migraña más frecuente (37.5% vs. 14%; p=0.03). Ninguna de las otras características clínicas y estudios complementarios fueron predictores de mayor riesgo de recurrencia. Conclusiones: los pacientes con migraña pueden tener un mayor riesgo de recurrencia de AGT. Ninguna de las otras características clínicas evaluadas nos permitió predecir un mayor riesgo de recurrencia. Aunque los estudios complementarios nos permitieron orientar el diagnóstico, no pareció tener un impacto significativo en la predicción del riesgo de recurrencia.

Prevalence of amyloid-ß pathology in distinct variants of primary progressive aphasia.

OBJECTIVE: To estimate the prevalence of amyloid positivity, defined by positron emission tomography (PET)/cerebrospinal fluid (CSF) biomarkers and/or neuropathological examination, in primary progressive aphasia (PPA) variants. METHODS: We conducted a meta-analysis with individual participant data from 1,251 patients diagnosed with PPA (including logopenic [lvPPA, n = 443], nonfluent [nfvPPA, n = 333], semantic [svPPA, n = 401], and mixed/unclassifiable [n = 74] variants of PPA) from 36 centers, with a measure of amyloid-ß pathology (CSF [n = 600], PET [n = 366], and/or autopsy [n = 378]) available. The estimated prevalence of amyloid positivity according to PPA variant, age, and apolipoprotein E (ApoE) ε4 status was determined using generalized estimating equation models. RESULTS: Amyloid-ß positivity was more prevalent in lvPPA (86%) than in nfvPPA (20%) or svPPA (16%; p < 0.001). Prevalence of amyloid-ß positivity increased with age in nfvPPA (from 10% at age 50 years to 27% at age 80 years, p < 0.01) and svPPA (from 6% at age 50 years to 32% at age 80 years, p < 0.001), but not in lvPPA (p = 0.94). Across PPA variants, ApoE ε4 carriers were more often amyloid-ß positive (58.0%) than noncarriers (35.0%, p < 0.001). Autopsy data revealed Alzheimer disease pathology as the most common pathologic diagnosis in lvPPA (76%), frontotemporal lobar degeneration-TDP-43 in svPPA (80%), and frontotemporal lobar degeneration-TDP-43/tau in nfvPPA (64%). INTERPRETATION: This study shows that the current PPA classification system helps to predict underlying pathology across different cohorts and clinical settings, and suggests that age and ApoE genotype should be considered when interpreting amyloid-ß biomarkers in PPA patients. Ann Neurol 2018;84:737-748.

Perception of stroke symptoms and utilization of emergency medical services.

METHODS: Review of hospital records and structured telephone interviews of 100 consecutive stroke patients. Forward stepwise logistic regression was used for the statistical analysis. RESULTS: Seventy patients (75%) arrived at the hospital 4.5 hours after stroke symptoms onset. The use of EMS did not improve arrival times. Most patients who recognized their symptoms did not use EMS (p < 0.02). Nineteen patients (20%) were initially misdiagnosed. Eighteen of them were first assessed by non-neurologist physicians (p < 0.001). CONCLUSIONS: Our population showed a low level of stroke awareness. The use of EMS did not improve arrival times at the hospital and the non-utilization of the EMS was associated with the recognition of stroke symptoms. There was a concerning rate of misdiagnosis, mostly by non-neurologist medical providers.

Perception of stroke symptoms and utilization of emergency medical services / Percepción de los síntomas del accidente cerebrovascular y utilización de los servicios de emergencias médicos

ABSTRACT Lack of stroke awareness and slow activation of emergency medical services (EMS) are frequently reported reasons for delayed arrival to the hospital. We evaluated these variables in our population. Methods Review of hospital records and structured telephone interviews of 100 consecutive stroke patients. Forward stepwise logistic regression was used for the statistical analysis. Results Seventy patients (75%) arrived at the hospital 4.5 hours after stroke symptoms onset. The use of EMS did not improve arrival times. Most patients who recognized their symptoms did not use EMS (p < 0.02). Nineteen patients (20%) were initially misdiagnosed. Eighteen of them were first assessed by non-neurologist physicians (p < 0.001). Conclusions Our population showed a low level of stroke awareness. The use of EMS did not improve arrival times at the hospital and the non-utilization of the EMS was associated with the recognition of stroke symptoms. There was a concerning rate of misdiagnosis, mostly by non-neurologist medical providers.

RESUMO La falta de reconocimiento de los síntomas del accidente cerebrovascular (ACV) y la lenta activación de los servicios de emergencias médicos (SEM) son causas frecuentes de demoras en el arribo hospitalario. Nuestro objetivo fue evaluar ambas variables en nuestra población. Métodos Revisión de registros hospitalarios y entrevista telefónica estructurada de 100 pacientes consecutivos internados por ACV. El análisis estadístico se realizó mediante un modelo de regresión logística multivariada por pasos. Resultados Setenta pacientes (75%) arribaron al hospital luego de 4.5 horas del comienzo de los síntomas. El uso de los SEM no mejoró los tiempos de arribo al hospital (p < 0.02). Inicialmente, 19 pacientes (20%) recibieron un diagnóstico erróneo. Dieciocho de ellos fueron evaluados por médicos no neurólogos. (p < 0.001). Conclusiones El reconocimiento de los síntomas de ACV en nuestra población fue bajo. El uso de los SEM no mejoró los tiempos de arribo hospitalario y la no utilización de los mismos se asoció con el correcto reconocimiento de los síntomas por parte de los pacientes. La proporción de diagnósticos erróneos fue preocupante, fundamentalmente entre médicos no neurólogos.

Anti-inflammatory effects of melatonin in multiple sclerosis.

Melatonin is a hormone with complex roles in the pathogenesis of autoimmune disorders. Over the years, it has become clear that melatonin may exacerbate some autoimmune conditions, whereas it alleviates others such as multiple sclerosis. Multiple sclerosis is an autoimmune disorder characterized by a dysregulated immune response directed against the central nervous system. Indeed, the balance between pathogenic CD4(+) T cells secreting IFN-γ (TH 1) or IL-17 (TH 17); and FoxP3(+) regulatory T cells and IL-10(+) type 1 regulatory T cells (Tr1 cells) is thought to play an important role in disease activity. Recent evidence suggests that melatonin ameliorates multiple sclerosis by controlling the balance between effector and regulatory cells, suggesting that melatonin-triggered signaling pathways are potential targets for therapeutic intervention. Here, we review the available data on the effects of melatonin on immune processes relevant for MS and discuss its therapeutic potential.

Síndrome de superposición entre miastenia grave y miopatías inflamatorias idiopáticas / Overlap syndrome between myasthenia gravis and idiopathic inflammatory myopathies

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Perivenular brain lesions in a primate multiple sclerosis model at 7-tesla magnetic resonance imaging.

BACKGROUND Magnetic resonance imaging (MRI) can provide in vivo assessment of tissue damage, allowing evaluation of multiple sclerosis (MS) lesion evolution over time--a perspective not obtainable with postmortem histopathology. Relapsing-remitting experimental autoimmune encephalomyelitis (EAE) is an experimental model of MS that can be induced in the common marmoset, a small new world primate, and that causes perivenular white matter (WM) lesions similar to those observed in MS. METHODS Brain lesion development and evolution were studied in vivo and postmortem in four marmosets with EAE through serial T2- and T2*-weighted scans at 7-tesla. Supratentorial WM lesions were identified and characterized. RESULTS Of 97 lesions observed, 86 (88%) were clearly perivenular, and 62 (72%) developed around veins that were visible even prior to EAE induction. The perivenular configuration was confirmed by postmortem histopathology. Most affected veins, and their related perivascular Virchow-Robin spaces, passed into the subarachnoid space rather than the ventricles. CONCLUSION As in human MS, the intimate association between small veins and EAE lesions in the marmoset can be studied with serial in vivo MRI. This further strengthens the usefulness of this model for understanding the process of perivenular lesion development and accompanying tissue destruction in MS.