Latin American consensus recommendations on the risk of infections in people with multiple sclerosis treated with disease modifying drugs.

INTRODUCTION: The emergence of several therapeutic options in multiple sclerosis (MS), which significantly modify the immune system functioning, has led to the need for the consideration of additional factors, such as risk of infections, in the decision-making process. The aim of these consensus recommendations was to discuss and perform a practical guide to Latin American neurologists on the risk of infections at diagnosis, follow-up and prior to initiation of DMDs. METHODS: A panel of Latin American neurologists, experts in demyelinating diseases and dedicated to management and care of MS patients, gathered during 2021 and 2022 to make consensus recommendations on the risk of infections in PwMS treated with DMDs in Latin America. The RAND/UCLA methodology was developed to synthesize the scientific evidence and expert opinions on health care topics and was used for reaching a formal agreement. RESULTS: Recommendations were established based on relevant published evidence and expert opinion, focusing on: 1- baseline infection disease and vaccination status; 2- opportunistic infections; 3- progressive multifocal leukoencephalopathy; 4- genitourinary system infections; 5- respiratory tract infections; 6- digestive system infections, 7-others local infections and 8- COVID-19. CONCLUSION: The recommendations of this consensus seek to optimize the care, management and treatment of PwMS in Latin America. The standardized evidence-based care of pwMS infections will allow better outcomes.

Hantavirus in Panama: Twenty Years of Epidemiological Surveillance Experience.

Twenty years have passed since the emergence of hantavirus zoonosis in Panama at the beginning of this millennium. We provide an overview of epidemiological surveillance of hantavirus disease (hantavirus pulmonary syndrome and hantavirus fever) during the period 1999-2019 by including all reported and confirmed cases according to the case definition established by the health authority. Our findings reveal that hantavirus disease is a low-frequency disease, affecting primarily young people, with a relatively low case-fatality rate compared to other hantaviruses in the Americas (e.g., ANDV and SNV). It presents an annual variation with peaks every 4-5 years and an interannual variation influenced by agricultural activities. Hantavirus disease is endemic in about 27% of Panama, which corresponds to agroecological conditions that favor the population dynamics of the rodent host, Oligoryzomys costaricensis and the virus (Choclo orthohantavirus) responsible for hantavirus disease. However, this does not rule out the existence of other endemic areas to be characterized. Undoubtedly, decentralization of the laboratory test and dissemination of evidence-based surveillance guidelines and regulations have standardized and improved diagnosis, notification at the level of the primary care system, and management in intensive care units nationwide.

An elevated parametric thyroid feedback quantile-based index is associated with atrial fibrillation.

Introduction: Atrial fibrillation is associated with hyperthyroidism. Within the euthyroid range, it is also associated with high thyroxine (fT4), but not with thyrotropin (TSH). We aim to describe differences in thyroid regulation, measured by the Parametric Thyroid Feedback Quantile-Based Index (PTFQI), between patients with atrial fibrillation and the general population. Materials and methods: Thyroid parameters (PTFQI, TSH, and fT4) of a sample of 84 euthyroid subjects with atrial fibrillation (cases) were compared to a reference sample of euthyroid healthcare patients (controls). We calculated age and sex adjusted ORs for atrial fibrillation across tertiles of these parameters. Also, within cases, we studied thyroid parameters association with clinical characteristics of the atrial fibrillation. Results: After adjusting for age and sex, fT4 and PTFQI were higher in subjects with atrial fibrillation when compared to the general sample (p<0.01 and p=0.01, respectively). Atrial fibrillation ORs of the third versus the first PTFQI tertile was 1.88(95%CI 1.07,3.42), and there was a gradient across tertiles (p trend=0.02). Among atrial fibrillation patients, we observed that higher PTFQI was associated with sleep apnea/hypopnea syndrome (OSAS) (p=0.03), higher fT4 was associated with the presence of an arrhythmogenic trigger (p=0.02) and with heart failure (p<0.01), and higher TSH was also associated with OSAS (p<0.01). Conclusions: Euthyroid subjects with atrial fibrillation have an elevation of the pituitary TSH-inhibition threshold, measured by PTFQI, with respect to the general population. Within atrial fibrillation patients, high PTFQI was associated with OSAS, and high fT4 with heart failure. These results hint of the existence of a relationship between thyroid regulation and atrial fibrillation.

Therapeutic strategies in NMOSD and MOGAD patients: A multicenter cohort study in Latin America.

PURPOSE: This study describes the therapeutic strategies in NMOSD and MOGAD adopted by neurologists to treat both conditions in Latin America (LATAM) with main focus on rituximab (RTX) and the disease outcome. METHODS: retrospective study in a cohort of NMOSD and MOGAD patients followed in specialized MS/NMOSD centers from eight countries and 14 LATAM reference centers. Demographics and clinical characteristics were collected. RTX strategies on naïve (for rituximab) patients were summarized as follows: scheme A: two 1000 mg infusions 15 days apart and repeated every 6 months; scheme B: four 375 mg/m2 infusions every week for 4 weeks and repeated every 6 months; scheme C: one 1000 mg infusions and repeated every 6 months; scheme D: other scheme used. Relapse rate and adverse events during follow-up were analyzed considering the different RTX schemes. Poisson and logistic regression analysis were used to assess baseline aspects and disease activity during follow-up. RESULTS: A total of 217 patients were included. 197 were NMOSD patients (164, 83.2% AQP4-IgG seropositive and 16.7% seronegative) and 20 were MOGAD patients. The most frequent long-term treatment was RTX in both groups (48.2% and 65% for NMOSD and MOGAD patients, respectively). The most common RTX regimen used in 79 (83.1%) patients was two 1000 mg infusions 15 days apart and repeat every 6 months. Relapses under RTX treatment were observed in 21 (22.1%) patients. Relapses after RTX treatment were associated with higher EDSS (OR 1.75, 95%CI 1.44-2.34, p = 0.03) and higher ARR pre-RTX (OR = 2.17, 95% CI 1.72-3.12, p = 0.002) but not with RTX regimen (OR = 1.10, 95% CI 0.89-1.21, p = 0.60). CONCLUSION: the most strategy used in LATAM was RTX with two 1000 mg infusions 15 days apart. Relapses during follow up were not associated with RTX regimen used.

Frequency of NMOSD misdiagnosis in a cohort from Latin America: Impact and evaluation of different contributors.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) misdiagnosis (i.e. the incorrect diagnosis of patients who truly have NMOSD) remains an issue in clinical practice. We determined the frequency and factors associated with NMOSD misdiagnosis in patients evaluated in a cohort from Latin America. METHODS: We retrospectively reviewed the medical records of patients with NMOSD, according to the 2015 diagnostic criteria, from referral clinics in six Latin American countries (Argentina, Chile, Paraguay, Colombia, Ecuador, and Venezuela). Diagnoses prior to NMOSD and ultimate diagnoses, demographic, clinical and paraclinical data, and treatment schemes were evaluated. RESULTS: A total of 469 patients presented with an established diagnosis of NMOSD (73.2% seropositive) and after evaluation, we determined that 56 (12%) patients had been initially misdiagnosed with a disease other than NMOSD. The most frequent alternative diagnoses were multiple sclerosis (MS; 66.1%), clinically isolated syndrome (17.9%), and cerebrovascular disease (3.6%). NMOSD misdiagnosis was determined by MS/NMOSD specialists in 33.9% of cases. An atypical MS syndrome was found in 86% of misdiagnosed patients, 50% had NMOSD red flags in brain and/or spinal magnetic resonance imaging (MRI), and 71.5% were prescribed disease-modifying drugs. CONCLUSIONS: NMOSD misdiagnosis is relatively frequent in Latin America (12%). Misapplication and misinterpretation of clinical and neuroradiological findings are relevant factors associated with misdiagnosis.

Mielinosis extrapontina: reporte de un caso de síndrome de desmielinización osmótica

Introducción: El síndrome de desmielinización osmótica es una entidad clínica la cual supone un reto diagnóstico por su curso en muchos casos silentes y por su cuadro clínico que se presenta típicamente de manera tardía. Se describen dos tipos de desmielinización osmótica que pueden presentarse de manera aislada o simultánea: la mielinosis central pontina y la mielinosis extrapontina. Caso clínico: femenina de 21 años sin antecedentes personales con episodio convulsivo tónico clónico por primera vez en su vida. Se le encuentra a su ingreso un nivel de sodio sérico disminuido, razón por la cual se inicia la corrección intravenosa del mismo. Cursó con cefaleas persistentes y vómitos a las 48 horas posterior a la corrección del sodio, y se realizó una resonancia magnética cerebral que evidenció datos de mielinosis extrapontina. Conclusión: La corrección rápida de los niveles de sodio se asocia a la posibilidad de desarrollar mielinosis pontina. La precaución en la corrección de la hiponatremia es la piedra angular para prevenir el desarrollo de esta condición. (provisto por Infomedic International)

Introduction: Osmotic demyelination syndrome is a clinical entity which poses a diagnostic challenge because of its often-silent course and its clinical picture which typically presents late. We describe two types of osmotic demyelination that can occur in isolation or simultaneously: central pontine myelinosis and extrapontine myelinosis. Case report: 21-year-old female with no personal history with tonic-clonic seizure episode for the first time in her life. On admission she was found to have a decreased serum sodium level, for which reason intravenous sodium correction was started. He presented with persistent headaches and vomiting 48 hours after sodium correction, and a brain MRI was performed, which showed evidence of extrapontine myelinosis. Conclusion: Rapid correction of sodium levels is associated with the possibility of developing pontine myelinosis. Caution in correcting hyponatremia is the cornerstone in preventing the development of this condition. (provided by Infomedic International)

Diagnosis and classification of optic neuritis.

There is no consensus regarding the classification of optic neuritis, and precise diagnostic criteria are not available. This reality means that the diagnosis of disorders that have optic neuritis as the first manifestation can be challenging. Accurate diagnosis of optic neuritis at presentation can facilitate the timely treatment of individuals with multiple sclerosis, neuromyelitis optica spectrum disorder, or myelin oligodendrocyte glycoprotein antibody-associated disease. Epidemiological data show that, cumulatively, optic neuritis is most frequently caused by many conditions other than multiple sclerosis. Worldwide, the cause and management of optic neuritis varies with geographical location, treatment availability, and ethnic background. We have developed diagnostic criteria for optic neuritis and a classification of optic neuritis subgroups. Our diagnostic criteria are based on clinical features that permit a diagnosis of possible optic neuritis; further paraclinical tests, utilising brain, orbital, and retinal imaging, together with antibody and other protein biomarker data, can lead to a diagnosis of definite optic neuritis. Paraclinical tests can also be applied retrospectively on stored samples and historical brain or retinal scans, which will be useful for future validation studies. Our criteria have the potential to reduce the risk of misdiagnosis, provide information on optic neuritis disease course that can guide future treatment trial design, and enable physicians to judge the likelihood of a need for long-term pharmacological management, which might differ according to optic neuritis subgroups.

Characteristics of migraine in patients with headache disorders: A clinic-based study from Central American and Caribbean countries.

OBJECTIVE: The objective of the study was to measure the proportion of patients who consulted for headache and of those who had a final diagnosis of migraine. We also assessed the proportion and characteristics of patients with migraine and the impact of migraine on the daily activities and the professional and social lives of patients visiting private/public medical centers in Guatemala, Costa Rica, Panama, and the Dominican Republic. BACKGROUND: Underdiagnosis of migraine is high in Central America and Caribbean urban communities. However, there is limited knowledge on characteristics of headache disorders for the appropriate classification of migraine, which is a prerequisite for targeted treatment. Hence, there is a need to improve migraine awareness among patients and medical professionals in this region. METHODS: Central America and Caribbean countries epidemioLogy study of Migraine (CALM) was a non-interventional, cross-sectional, multinational study in adults aged 18-65 years with a history of or current headache. The primary outcome was the proportion of patients with migraine visiting medical centers due to headache disorders. Using a specially designed migraine survey questionnaire, patients self-reported migraine characteristics, duration, and severity of attacks and impact on work and social life. RESULTS: Of the 313 enrolled patients, 308 (98.4%) completed the study. Approximately 75.3% (232/308) of patients with headache visiting medical centers had migraine, with episodic migraine being the most common (193 [83.2%]). Overall, 34/308 (11.0%) patients had a new diagnosis of migraine. Among patients with migraine, 66 (28.4%) had a history of migraine for ≥20 years and 59 (25.4%) experienced severe pain. Overall, 52.2% (121/232) of patients reported that migraine affected their professional life and 78.4% (182/232) reported an impact on social life. CONCLUSION: The CALM study establishes that a high proportion of patients with migraine had a long duration and high severity of migraine attacks, leading to a direct impact on work/social life as well as on costs incurred by patients in these countries.

Enfermedad de Huntington en población panameña, 2007-2021

Introducción: La enfermedad de Huntington (EH) es un desorden neurodegenerativo autosómico dominante caracterizado por disfunción progresiva motora, cognitiva y psiquiátrica1. No se conoce la prevalencia de EH en Centro América (2-11). En Panamá no se han reportado estudios sobre esta Enfermedad. El objetivo es estimar la prevalencia de EH en población panameña. Metodología: Se realizó un estudio descriptivo de casos con EH entre 2007 y 2021 en un hospital de tercer nivel. Se incluyeron individuos panameños, mayores de 15 años, un caso por familia, con cuadro clínico sugestivo, con o sin antecedentes familiares, resonancia magnética cerebral y prueba genética HTT positiva. Estos casos fueron incluidos en el Registro Nacional de Enfermedad de Huntington. Resultados: Presentamos 11 casos índice, 6 femeninos.  Se estima una prevalencia de 0.25 x 100000 habitantes, edad promedio 40 años (rango 23-63), media 43±12.4, la edad de inicio 29 años (rango 14-43), media 27±11.13, presentación juvenil 3 casos. Se detectaron 91 sintomáticos de 185 familiares, transmisión predominante paterna, todos heterocigóticos. Alelo normal entre 13-23 repeticiones de CAG, mientras que alelo mutante oscila entre 41 y 59 repeticiones de CAG. Conclusión: Este es el primer reporte de la EH en población panameña, la prevalencia estimada es baja de 0.25 x 100000 habitantes. Estudios futuros deberán realizarse para conocer la prevalencia en Panamá y Centro América además de determinar el origen ancestral de esta población. (provisto por Infomedic International)

Introduction: Huntington´s disease (HD) is an autosomal dominant neurodegenerative disorder characterized by progressive motor, cognitive and psychiatric dysfunction. HD prevalence in Panama or in Central America is unknown. This will be the first report in Panamá about HD. Metodology: The objective is to estimate HD prevalence in Panamanian population. A retrospective, descriptive study of patients with HD between 2007 and 2021 was conducted. Panamanians > 15 years, 1 case per family, with typical clinical symptoms, with or without family history, brain magnetic resonance and positive genetic test and then included in the National registry of Huntington Disease. Results: Eleven index cases were presented, 6 women. The mean age was 40 years (range 23-63), median 43±12.4, sex ratio was 5:6, the onset age was 29 years (range 14-43), median 27±11.13. 3 cases in young patients. 91 symptomatic cases out of 185 relatives, with a dominant paternal transmission, all heterozygous. Normal allele between 13-23 CAG repetitions, while the mutant allele ranges between 41 and 59 CAG repetitions. Conclusions: This is the first HD report in Panamanian population, with a low estimated prevalence of 0.25 x 100,000. The aim of this study is to promote HD research in Panama and Central America and determine the ancestral origin of this population. (provided by Infomedic International)

A Cross-Sectional Study Examining the Parametric Thyroid Feedback Quantile Index and Its Relationship with Metabolic and Cardiovascular Diseases.

Background: The usual inverse correlation between thyrotropin (TSH) and thyroid hormone disappears in syndromes of central resistance to thyroid hormone, where both are high. TSH and thyroid hormone are also simultaneously high when there is an elevation of the set point of the thyroid regulation axis. This can be estimated with indices, such as the Parametric Thyroid Feedback Quantile-based Index (PTFQI), which was designed for the general population. The PTFQI is positively associated with diabetes prevalence, but association with other pathologies has not been yet explored. The aim of this project was to explore the potential relationship of the PTFQI with metabolic and cardiovascular disease in a sample of ambulatory adult patients from Spain. Methods: A cross-sectional study was carried out among the patients who underwent thyroid hormones measurement (6434 measurements from September to November 2018 in a central laboratory in Spain). We retrospectively reviewed clinical records of a subgroup of adults aged >18 years with normal TSH and free thyroxine (fT4) belonging to groups that represent extreme PTFQI (n = 661). Individuals with known conditions interfering the thyroid axis were excluded (remaining n = 296). Logistic and linear regression models adjusted for age and sex were used to calculate odds ratio (OR) of diseases and differences of clinical parameters, and 95% confidence intervals [CI]. Results: Across levels with higher PTFQI, there was an increase in the prevalence of type 2 diabetes (High vs. Low PTFQI OR: 2.88 [CI: 1.14-7.86], p-Trend = 0.02), ischemic heart disease (16.4% vs. 0%, unadjusted Haldane-Anscombe corrected OR: 23.90 [CI: 1.36-21.48], adjusted p-Trend = 0.04), atrial fibrillation (OR: 8.13 [CI: 1.33-158.20], p-Trend = 0.05), and hypertension (OR: 3.19 [CI: 1.14-9.94], p-Trend = 0.05). While the prevalence of type 2 diabetes was similarly associated with TSH and fT4, ischemic heart disease, atrial fibrillation, and hypertension were more strongly associated with the differences in fT4 values. Conclusions: Type 2 diabetes, ischemic heart disease, atrial fibrillation, and hypertension may be associated with a higher central regulation set point for thyroid hormone. These findings should be confirmed in other populations.

Neuromyelitis Optica Spectrum Disorder in Central America and the Caribbean: A Multinational Clinical Characterization Study.

Here, a study of NMOSD in Central America and the Caribbean with a multinational collaborative, multicentric and descriptive approach involving 25 institutions from 9 countries is presented. Demographics, clinical manifestations, expanded disability scale status (EDSS), brain and spinal cord MRI, serological anti-AQP4-IgG and anti-MOG-IgG antibodies, and cerebrospinal fluid (CSF) oligoclonal bands were included. A central serological repository utilized the cell-based assay. The specimens outside of this network employed diverse methodologies. Data were collected at the Gorgas Commemorative Institute of Health Studies (ICGES), Panama, and included 186 subjects, of which 84% were females (sex ratio of 5.6:1). Mestizos constituted 72% of the study group. The median age was 42.5 years (IQR: 32.0-52.0). Associated autoimmune diseases (8.1%) were myasthenia gravis, Sjögren's syndrome and systemic lupus erythematosus. The most common manifestation was optic neuritis-transverse myelitis (42.5%). A relapsing course was described in 72.3% of cases. EDSS scores of 0-3.5 were reported in 57.2% of cases and higher than 7.0 in 14.5%. Positive anti-AQP4-IgG antibody occurred in 59.8% and anti-MOG-IgG antibody in 11.5% of individuals. Antibody testing was lacking for 13.4% of patients. The estimated crude prevalence of NMOSD from Panama and the Dominican Republic was 1.62/100,000 (incidence of 0.08-0.41) and 0.73/100,000 (incidence 0.02-0.14), respectively. This multinational study contributes additional insights and data on the understanding of NMOSD in this Latin American region.

Multiple sclerosis care units in Latin America: Consensus recommendations about its objectives and functioning implementation.

OBJECTIVE: Currently, there are several reasons to promote worldwide the concept of multiple sclerosis care units (MSCU) for a better management of affected patients. Ideally, the MSCU should have some human and technical resources that distinguish and improve the care of affected patients; however, local, and regional aspects should be considered when recommending how these units should operate. The objective of these consensus recommendations was to review how MSCU should work in Latin America to improve long-term outcomes in MS patients. METHODS: A panel of neurology experts from Latin America dedicated to the diagnosis and care of MS patients gathered virtually during 2019 and 2020 to carry out a consensus recommendation about objectives and functioning implementation of MSCU in Latin America. To achieve consensus, the methodology of "formal consensus-RAND/UCLA method" was used. RESULTS: Recommendations focused on the objectives, human and technical resources, and the general functioning that MSCU should have in Latin America. CONCLUSIONS: The recommendations of these consensus guidelines attempt to optimize the health care and management of MS patients by setting how MSCU should work in our region.

Multiple sclerosis and neuromyelitis optica spectrum disorder testing and treatment availability in Latin America.

BACKGROUND: The objective of our study was to describe the availability of diagnostic tests and treatment for MS and NMOSD in Latin America (LATAM). METHODS: A survey instrument was used in a sample of physicians from LATAM countries. The goal of the survey was to understand availability of: 1) imaging tests for diagnosing MS and NMOSD and its barriers; 2) diagnostic laboratory tests for diagnosing MS and NMOSD and its barriers; and 3) treatments for MS and NMOSD in the acute and chronic phases of the disease. RESULTS: Responses were received from 80 physicians. AQP4-ab test was available in 54% of the countries and MOG-ab test in 42%. All of countries had available use of high doses of intravenous methylprednisolone, oral steroids, plasmapheresis, and intravenous immunoglobulins for relapses. For NMOSD, 93% of the countries were able to use azathioprine and mycophenolate mofetil, and 87% rituximab. In MS, 93% of countries had available to them IFN beta, 69% glatiramer acetate, 75% teriflunomide, 93% fingolimod, 69% dimethyl-fumarate, 75% cladribine, 69% natalizumab, 93% ocrelizumab and 81% alemtuzumab. The most common challenge and barrier identified was the cost of medications. CONCLUSION: The present study allows an understanding of the delivery of care for MS and NMOSD in the region.

Status of the neuromyelitis optica spectrum disorder in Latin America.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) is an increasing diagnostic and therapeutic challenge in Latin America (LATAM). Despite the heterogeneity of this population, ethnic and socioeconomic commonalities exist, and epidemiologic studies from the region have had a limited geographic and population outreach. Identification of some aspects from the entire region are lacking. OBJECTIVES: To determine ethnic, clinical characteristics, and utilization of diagnostic tools and types of therapy for patients with NMOSD in the entire Latin American region. METHODS: The Latin American Committee for Treatment and Research in MS (LACTRIMS) created an exploratory investigational survey addressed by Invitation to NMOSD Latin American experts identified through diverse sources. Data input closed after 30 days from the initial invitation. The questionnaire allowed use of absolute numbers or percentages. Multiple option responses covering 25 themes included definition of type of practice; number of NMOSD cases; ethnicity; utilization of the 2015 International Panel criteria for the diagnosis of Neuromyelitis optica (IPDN); clinical phenotypes; methodology utilized for determination of anti-Aquaporin-4 (anti- AQP4) antibodies serological testing, and if this was performed locally or processed abroad; treatment of relapses, and long-term management were surveyed. RESULTS: We identified 62 investigators from 21 countries reporting information from 2154 patients (utilizing the IPDN criteria in 93.9% of cases), which were categorized in two geographical regions: North-Central, including the Caribbean (NCC), and South America (SA). Ethnic identification disclosed Mestizos 61.4% as the main group. The most common presenting symptoms were concomitant presence of optic neuritis and transverse myelitis in 31.8% (p=0.95); only optic neuritis in 31.4% (more common in SA), p<0.001); involvement of the area postrema occurred in 21.5% and brain stem in 8.3%, both were more frequent in the South American cases (p<0.001). Anti-AQP4 antibodies were positive in 63.9% and anti-Myelin Oligodendrocyte Glycoprotein (MOG) antibodies in 4.8% of total cases. The specific laboratorial method employed was not known by 23.8% of the investigators. Acute relapses were identified in 81.6% of cases, and were treated in 93.9% of them with intravenous steroids (IVS); 62.1% with plasma exchange (PE), and 40.9% with intravenous immunoglobulin-G (IVIG). Therapy was escalated in some cases due to suboptimal initial response. Respondents favored Rituximab as long-term therapy (86.3%), whereas azathioprine was also utilized on 81.8% of the cases, either agent used indistinctly by the investigators according to treatment accessibility or clinical judgement. There were no differences among the geographic regions. CONCLUSIONS: This is the first study including all countries of LATAM and the largest cohort reported from a multinational specific world area. Ethnic distributions and phenotypic features of the disease in the region, challenges in access to diagnostic tools and therapy were identified. The Latin American neurological community should play a determinant role encouraging and advising local institutions and health officials in the availability of more sensitive and modern diagnostic methodology, in facilitating the the access to licensed medications for NMOSD, and addressing concerns on education, diagnosis and management of the disease in the community.

Research priorities in multiple sclerosis in Latin America: A multi-stakeholder call to action to improve patients care: Research priorities in MS in LATAM.

As human and economic resources are limited, especially in Latin America (LATAM), it is important to identify research priorities to improve multiple sclerosis (MS) patients care in the region. The objective was to generate a multidisciplinary consensus on research priorities in MS for patients care in LATAM by involving healthcare professionals and MS patient associations. METHODS: consensus was reached through a four-step modified Delphi method designed to identify and rate research priorities in MS in LATAM. The process consisted of two qualitative assessments, a general ranking phase and a consensus meeting followed by a more detailed ranking phase RESULTS: a total of 62 participants (35 neurologists, 4 nurses, 12 kinesiologists, 7 neuropsychologists and 4 patient association members) developed the process. At the final ranking stage following the consensus meeting, each participant provided their final rankings, and the top priority research questions were outlined. 11 research priorities were identified focusing on healthcare access, costs of the disease, physical and cognitive evaluation and rehabilitation, quality of life, symptoms management, prognostic factors, the need of MS care units and patient's management in emergencies like COVID-19. CONCLUSION: this work establishes MS research priorities in LATAM from multiple perspectives. To pursue the actions suggested could launch the drive to obtain information that will help us to better understand the disease in our region and, especially, to better care for affected patients.

Acute Transverse Myelitis (ATM):Clinical Review of 43 Patients With COVID-19-Associated ATM and 3 Post-Vaccination ATM Serious Adverse Events With the ChAdOx1 nCoV-19 Vaccine (AZD1222).

Introduction: Although acute transverse myelitis (ATM) is a rare neurological condition (1.34-4.6 cases per million/year) COVID-19-associated ATM cases have occurred during the pandemic. Case-finding methods: We report a patient from Panama with SARS-CoV-2 infection complicated by ATM and present a comprehensive clinical review of 43 patients with COVID-19-associated ATM from 21 countries published from March 2020 to January 2021. In addition, 3 cases of ATM were reported as serious adverse events during the clinical trials of the COVID-19 vaccine ChAdOx1 nCoV-19 (AZD1222). Results: All patients had typical features of ATM with acute onset of paralysis, sensory level and sphincter deficits due to spinal cord lesions demonstrated by imaging. There were 23 males (53%) and 20 females (47%) ranging from ages 21- to 73- years-old (mean age, 49 years), with two peaks at 29 and 58 years, excluding 3 pediatric cases. The main clinical manifestations were quadriplegia (58%) and paraplegia (42%). MRI reports were available in 40 patients; localized ATM lesions affected ≤3 cord segments (12 cases, 30%) at cervical (5 cases) and thoracic cord levels (7 cases); 28 cases (70%) had longitudinally-extensive ATM (LEATM) involving ≥4 spinal cord segments (cervicothoracic in 18 cases and thoracolumbar-sacral in 10 patients). Acute disseminated encephalomyelitis (ADEM) occurred in 8 patients, mainly women (67%) ranging from 27- to 64-years-old. Three ATM patients also had blindness from myeloneuritis optica (MNO) and two more also had acute motor axonal neuropathy (AMAN). Conclusions: We found ATM to be an unexpectedly frequent neurological complication of COVID-19. Most cases (68%) had a latency of 10 days to 6 weeks that may indicate post-infectious neurological complications mediated by the host's response to the virus. In 32% a brief latency (15 hours to 5 days) suggested a direct neurotropic effect of SARS-CoV-2. The occurrence of 3 reported ATM adverse effects among 11,636 participants in the AZD1222 vaccine trials is extremely high considering a worldwide incidence of 0.5/million COVID-19-associated ATM cases found in this report. The pathogenesis of ATM remains unknown, but it is conceivable that SARS-CoV-2 antigens -perhaps also present in the AZD1222 COVID-19 vaccine or its chimpanzee adenovirus adjuvant- may induce immune mechanisms leading to the myelitis.

COVID-19 in multiple sclerosis and neuromyelitis optica spectrum disorder patients in Latin America: COVID-19 in MS and NMOSD patients in LATAM.

BACKGROUND: There is no data regarding COVID-19 in Multiple Sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) patients in Latin America. OBJECTIVE: The objective of this study was to describe the clinical characteristics and outcomes of patients included in RELACOEM, a LATAM registry of MS and NMOSD patients infected with COVID-19. METHODS: RELACOEM is a longitudinal, strictly observational registry of MS and NMOSD patients who suffer COVID-19 and Dengue in LATAM. Inclusion criteria to the registry were either: (1) a biologically confirmed COVID-19 diagnosis based on a positive result of a COVID-19 polymerase chain reaction (PCR) test on a nasopharyngeal swab; or (2) COVID-19-typical symptoms (triad of cough, fever, and asthenia) in an epidemic zone of COVID-19. Descriptive statistics were performed on demographic and clinical variables. The cohort was later stratified for MS and NMOSD and univariate and multivariate logistic regression analysis was performed to identify variables associated with hospitalizations/intensive critical units (ICU) admission. RESULTS: 145 patients were included in the registry from 15 countries and 51 treating physicians. A total of 129 (89%) were MS patients and 16 (11%) NMOSD. 81.4% patients had confirmed COVID-19 and 18.6% were suspected cases. 23 (15.8%) patients were hospitalized, 9 (6.2%) required ICU and 5 (3.4 %) died due to COVID-19. In MS patients, greater age (OR 1.17, 95% CI 1.05 - 1.25) and disease duration (OR 1.39, 95%CI 1.14-1.69) were associated with hospitalization/ICU. In NMOSD patients, a greater age (54.3 vs. 36 years, p=<0.001), increased EDSS (5.5 vs 2.9, p=0.0012) and disease duration (18.5 vs. 10.3 years, p=0.001) were significantly associated with hospitalization/ICU. CONCLUSION: we found that in MS patients, age and disease duration was associated with hospitalization and ICU admission requirement, while age, disease duration and EDSS was associated in NMOSD.

Clinical and Nutritional Effectiveness of a Nutritional Protocol with Oligomeric Enteral Nutrition in Patients with Oncology Treatment-Related Diarrhea.

(1) Background: Poor nutritional status and diarrhea are common complications in cancer patients. (2) Methods: This multicenter, observational, prospective study evaluated the effectiveness of an oligomeric enteral nutrition (OEN) protocol in the improvement of nutritional status and reduction of diarrhea symptoms. Nutritional status was assessed with the Subjective Global Assessment (SGA), Body Mass Index (BMI) and albumin levels. Diarrhea was evaluated by the frequency and consistency of stools (Bristol Stool form scale). (3) Results: After 8 weeks of OEN protocol, the nutritional status improved in 48.3% of patients, with an increased proportion of patients at risk of malnourishment (+27.3%) at the expense of a decrease of moderately (-19.9%) and severely (-7.3%) malnourished patients (p < 0.001). Serum albumin and BMI significantly increased after 8 weeks of OEN treatment (p < 0.005). OEN showed a 71.1% effectiveness in the improvement of stool consistency. The mean number of stools per day significantly decreased from baseline (4.17 stools/day) to week 8 (1.42 stools/day; p = 0.0041). The nutritional status significantly improved even in those patients with persistent diarrhea. (4) Conclusion: The proposed OEN protocol seemed to be effective in improving the nutritional status, frequency and consistency of stools in patients with oncology treatment-related diarrhea even in persistent cases.

Impact of an Oral Nutritional Protocol with Oligomeric Enteral Nutrition on the Quality of Life of Patients with Oncology Treatment-Related Diarrhea.

(1) Background: Nutritional status can influence the quality of life (QoL) of cancer patients. (2) Methods: This subanalysis evaluated the impact of an oral oligomeric enteral nutrition (OEN) protocol on the QoL of patients with oncology treatment-related diarrhea (OTRD) in a multicenter, observational, prospective study (DIAPOENO study). QoL was assessed with the Nottingham Health Profile (NHP) at baseline and after eight weeks of OEN treatment. (3) In the overall population, all the NHP categories significantly improved after eight weeks of OEN treatment: energy levels (p < 0.001), pain (p < 0.001), emotional reactions (p < 0.001), sleep (p < 0.001), social isolation (p = 0.023), and physical abilities (p = 0.001). QoL improvement was higher in patients with improved or maintained nutritional status and in those with improved consistency of stools with the OEN protocol. However, QoL did not significantly improve in patients with worse nutritional status and with worse or maintained stool consistency with the OEN protocol. QoL improved regardless of disease severity. Multivariate logistic regression analysis showed that weight change was significantly associated with improved QoL (OR 2.90-5.3), except for social isolation, in models unadjusted and adjusted to age, sex, oncology treatment, and stool consistency. (4) Conclusion: In this subanalysis, the OEN protocol was associated with improved QoL.

Oligomeric Enteral Nutrition in Undernutrition, due to Oncology Treatment-Related Diarrhea. Systematic Review and Proposal of An Algorithm of Action.

Oncology treatment-related diarrhea and malnutrition appear together in oncological patients because of the disease itself, or the treatments that are administered for it. Therefore it is essential to carry out a nutritional treatment. Enteral nutrition formulas, containing peptides and medium chain triglycerides, can facilitate absorption in cases of malabsorption. There are few references to the use of enteral nutrition in the clinical society guidelines of patient management with oncology treatment-related diarrhea (OTRD). A bibliographic review of the studies with oligomeric enteral nutrition in OTRD found only nine studies with chemotherapy (all with the same oligomeric formula in which oral mucositis improves, while the rest of the outcomes show different results), and eight studies with radiotherapy (with different products and very heterogeneous results). We hereby present our action algorithm to supplement the diet of OTRD patients with an oligomeric enteral nutrition formula. The first step is the nutritional assessment, followed by the assessment of the functional capacity of the patient's intestine. With these two aspects evaluated, the therapeutic possibilities available vary in degrees of complexity: These will range from the usual dietary recommendations, to supplementation with oral oligomeric enteral nutrition, along with complete enteral nutrition with oligomeric formula, and up to potentially total parenteral nutrition.