Publications by authors named "Edgar Carnero Contentti"

59 Publications

The frequency of myelin oligodendrocyte glycoprotein antibodies in aquaporin-4-IgG-negative neuromyelitis optica spectrum disorders patients in Latin America.

Mult Scler Relat Disord 2021 Jun 30;54:103122. Epub 2021 Jun 30.

Centro de Esclerosis Múltiple de Buenos Aires (CEMBA), Buenos Aires, Argentina; Neurology Service, Hospital Universitario de CEMIC, Buenos Aires, Argentina.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msard.2021.103122DOI Listing
June 2021

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

Neurol Res 2021 Jul 9:1-6. Epub 2021 Jul 9.

Department of Neurology, Centro de esclerosis múltiple de Buenos Aires, Buenos Aires, Argentina.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/01616412.2021.1949686DOI Listing
July 2021

Family planning in Argentinian women with multiple sclerosis: An important yet seldom approached issue.

Mult Scler J Exp Transl Clin 2021 Apr-Jun;7(2):20552173211025312. Epub 2021 Jun 16.

Servicio de Neurología, Sanatorio Güemes, Buenos Aires, Argentina.

Background: The purpose of this study was to assess family planning (FP) among women with multiple sclerosis (WwMS).

Methods: We invited 604 WwMS to answer a survey focused on FP: a) Temporal relationship between pregnancy and the diagnosis of multiple sclerosis; b) History of FP; c) Childbearing desire; d) Information on family planning. Comparisons between pregnancy and not pregnancy after MS, as well as, planned and unplanned pregnancy were analyzed. Multivariate and univariate analyses were used to assess the impact of independent variables and FP.

Result: 428 (71.7%) WwMS completed the survey. A 19.1% got pregnant after MS diagnosis and we evaluated FP in the last pregnancy, 56.1% patients had a planned pregnancy. Professional addressing FP (OR = 0.27, 95%-CI 0.08-0.92, p = 0.03) and non-injection drug treatment before pregnancy (OR = 2.88, 95%-CI 1.01-8.21, p = 0.047) were independent predictors of unplanned pregnancy in our multivariate model. Among WwMS ≤ 40 years, 48.7% had future childbearing desire. Young age (p < 0.001), PDDS <3 (p = 0.018), disease duration <5 years (p = 0.02), not childbearing before MS diagnosis (p < 0.001) and neurologist addressing family planning (p = 0.01) were significantly associated with childbearing desire.

Conclusions: This research highlights that pregnancy remains an important concern among WwMS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/20552173211025312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216353PMC
June 2021

Interleukin-35 is a critical regulator of immunity during helminth infections associated with multiple sclerosis.

Immunology 2021 Jul 1. Epub 2021 Jul 1.

Neuroimmunology Unit, Department of Neuroscience, Hospital Alemán, Buenos Aires, Argentina.

Multiple sclerosis (MS) is currently thought to arise by interactions between genetic susceptibility and environmental factors. Infections in general trigger autoimmune responses causing clinical manifestations of disease. However, as a result of regulatory T (Treg)- and regulatory B (Breg)-cell induction, helminth infections tend to dampen disease activity. IL-35, the newest member of the IL-12 family, is an inhibitory cytokine composed of an EBI3β chain subunit, and an IL-12p35 subunit. The aim of this study was to investigate the role of IL-35 during parasite infections occurring in individuals with MS. Numbers of IL-35-producing Breg cells are higher in CSF from helminth-infected than from uninfected MS subjects, a finding associated with decreased MRI disease activity. Interestingly, stimulation of CD19 B cells with IL-35 promotes conversion of these cells to Breg cells producing both IL-35 and IL-10. Coculture of B cells from helminth-infected MS patients inhibits proliferation of Th1 and Th17 myelin peptide-specific T cells, as well as production of IFN-γ and IL-17. Following activation, CD4 CD25 Treg cells significantly upregulate expression of EBI3 and IL-12p35 mRNA. Furthermore, CD4 CD25 T cells activated in the presence of IL-35 induce a population of cells with regulatory function, known as iTR35. Finally, B cells from normal individuals cultured in vitro in the presence of the helminth antigen SEA increase expression of the transcription BATF, IRF4 and IRF8, acquiring a pattern similar to that of IL-35 Breg cells. These data highlight the important immunoregulatory effects of IL-35 on both Breg and Treg cells, observed in helminth-infected MS subjects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/imm.13389DOI Listing
July 2021

Status of the neuromyelitis optica spectrum disorder in Latin America.

Mult Scler Relat Disord 2021 Jun 15;53:103083. Epub 2021 Jun 15.

Hospital Universitario de Maracaibo y Policlínica Maracaibo, Maracaibo, Venezuela.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msard.2021.103083DOI Listing
June 2021

Real-world experience of ocrelizumab in multiple sclerosis patients in Latin America.

Arq Neuropsiquiatr 2021 04;79(4):305-309

Centro de Esclerosis Múltiple de Buenos Aires, Buenos Aires, Argentina.

Background: Despite the abundance of information concerning ocrelizumab in phase III clinical trials, there is scarce evidence regarding real-world patient profiles.

Objective: The aim of this study was to investigate patient profiles, effectiveness and persistence with treatment among patients who used ocrelizumab for treatment of multiple sclerosis in Latin America.

Methods: This was a retrospective multicenter study in Argentina, Chile and Mexico. Medical record databases on patients who received ocrelizumab were analyzed. Demographic and clinical variables were described, along with effectiveness outcomes, which included the proportions of patients free from clinical relapses, from disability progression and from new or enlarging T2 or T1 gadolinium-enhancing lesions, on annual magnetic resonance imaging.

Results: A total of 81 patients were included. The most frequent phenotype was relapsing-remitting MS, in 64.2% of the patients. The mean age at study entry was 41.3 ± 12.0 years and 51.8% were women. A total of 38% had had relapse activity during the 12 months before starting on ocrelizumab, with a mean relapse rate of 1.3 ± 0.6 during that period. 75% were free from clinical relapses and 91% were free from gadolinium-enhancing lesions in the relapsing-remitting course. Ocrelizumab discontinuation during the first 12 months was observed in three patients (3.7%). The mean persistence observed during the first-year follow-up was 338 ± 24 days.

Conclusions: Our study is in line with previous randomized clinical trials and recent real-world studies describing patient profiles, effectiveness and persistence regarding ocrelizumab treatment in multiple sclerosis patients in Latin America.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1590/0004-282X-ANP-2020-0339DOI Listing
April 2021

COVID-19 in Argentine teriflunomide-treated multiple sclerosis patients: First national case series.

Mult Scler Relat Disord 2021 May 30;53:103049. Epub 2021 May 30.

Centro de Esclerosis Múltiple de Buenos Aires, CABA; Argentina; Servicio de Neurología, Hospital Universitario CEMIC, Buenos Aires, Argentina.

We report COVID-19 presentation, course and outcomes in teriflunomide-treated MS patients in Argentina.

Methods: descriptive, retrospective, multicentre, study that included MS patients receiving teriflunomide who developed COVID-19, with clinical follow-up at reference MS centres, also listed in a nationwide registry.

Results: Eighteen MS patients on teriflunomide treatment, from eight MS centres developed COVID-19. The mean age was 41,2 years and 72% of them were female; 94% had diagnosis of relapsing-remitting MS and 6% presented a radiologically isolated syndrome. Median EDSS was 2 (range 0-5.5). The average time on teriflunomide therapy was 3 years. COVID-19 diagnosis was confirmed with nasal swab in 61%. None required hospitalization and they completely recovered from the acute-phase within 7-14 days. All the patients continued their teriflunomide therapy during COVID-19 course. No MS relapses occurred during or after COVID-19 course.

Conclusion: Our report adds to the evidence that COVID-19 is mild in patients receiving teriflunomide therapy and that continuing with teriflunomide therapy during Sars-CoV-2 infection is safe and advisable for MS patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msard.2021.103049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164731PMC
May 2021

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

Mult Scler Relat Disord 2021 May 24;53:103038. Epub 2021 May 24.

nstituto Nacional de Neurología y Neurocirugía "MVS", Ciudad de México, México.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msard.2021.103038DOI Listing
May 2021

Aggressive multiple sclerosis in Argentina: Data from the nationwide registry RelevarEM.

J Clin Neurosci 2021 Jul 1;89:360-364. Epub 2021 Jun 1.

Neuroimmunology Unit, Department of Neuroscience, Hospital Aleman, Buenos Aires, Argentina.

The objectives of the present study were to describe the frequency of aggressive multiple sclerosis (aMS) as well as to compare clinical and radiological characteristics in aMS and non-aMS patients included in RelevarEM (NCT03375177).

Methods: The eligible study population and cohort selection included adult-onset patients (≥18 years) with definite MS. AMS were defined as those reaching confirmed EDSS ≥ 6 within 5 years from symptom onset. Confirmation was achieved when a subsequent EDSS ≥ 6 was recorded at least six months later but within 5 years of the first clinical presentation. AMS and non-aMS were compared using the χ2 test for categorical and the Mann-Whitney for continuous variables at MS onset and multivariable analysis was performed using forward stepwise logistic regression with baseline characteristics at disease onset.

Results: A total of 2158 patients with MS were included: 74 aMS and 2084 non-aMS. The prevalence of aMS in our cohort was 3.4% (95%CI 2.7-4.2). AMS were more likely to be male (p = 0.003), older at MS onset (p < 0.001), have primary progressive MS (PPMS) phenotype (p = 0.03), multifocal presentation (p < 0.001), and spinal cord as well as infratentorial lesions at MRI during disease onset (p = 0.004 and p = 0.002, respectively).

Conclusion: 3.4% of our patient population could be considered aMS. Men, patients older at symptom onset, multifocal presentation, PPMS phenotype, and spinal cord as well as brainstem lesions on MRI at clinical presentation all had higher odds of having aMS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jocn.2021.05.047DOI Listing
July 2021

Employment status in people with relapsing multiple sclerosis from Argentina: Impact of disability and neuropsychological factors.

Work 2021 ;68(4):1171-1177

Neuroimmunology Unit, Department of Neuroscience, Hospital Alemán, Buenos Aires, Argentina.

Background: Unemployment is common in people with multiple sclerosis (PwMS) and might be prevented if factors associated with work loss are identified.

Objective: We aimed to assess the impact of multiple sclerosis (MS) on employment status in a cohort of PwMS from Argentina and to evaluate their association with anxiety, depression, fatigue and disability.

Methods: A cross-sectional study was conducted to assess employment in PwMS using an anonymous, self-administered questionnaire, which also included the Hospital Anxiety and Depression Scale, Fatigue Severity Scale and Expanded Disability Status Scale. The data was compared between employed (full-time vs. part-time) vs. unemployed (looking for vs. not looking for work) PwMS. Univariate and multivariate models were designed to identify factors independently associated with unemployment.

Results: Among the 167 PwMS, 120 (71.6%, full-time = 65%) were employed, and 47 (28.4%, looking for work = 27.6%) were currently unemployed. Age, gender, and duration of disease were similar in both groups. Univariate analysis showed that anxiety, depression, fatigue and disability were significantly associated with unemployed PwMS. However, only disability (OR = 1.36 (1.08-1.70), p = 0.007) was independently associated with unemployment after applying multivariate analysis (logistic regression).

Conclusion: Nearly one-third of PwMS from this sample in Argentina were unemployed. Neuropsychological factors and disability were associated with unemployment status.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/WOR-213446DOI Listing
June 2021

Emerging drugs for the treatment of adult MOG-IgG-associated diseases.

Expert Opin Emerg Drugs 2021 Jun 25;26(2):75-78. Epub 2021 Apr 25.

Department of Neurology, Fleni, Buenos Aires, Argentina.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14728214.2021.1919082DOI Listing
June 2021

Use of cannabis in patients with multiple sclerosis from Argentina.

Mult Scler Relat Disord 2021 Jun 6;51:102932. Epub 2021 Apr 6.

Neurology Department, Hospital J.M. Ramos Mejía, Faculty of Medicine, University of Buenos Aires, Buenos Aires, Argentina.

Background: The use of cannabis to treat some symptoms of neurological diseases, including multiple sclerosis (MS), has increased worldwide. We aimed to assess the use of cannabis in patients with MS (PwMS) from Argentina, its reasons and patients' perceptions on the management of MS symptoms. Additionally, we assessed their association with socio-demographic and clinical aspects.

Methods: A cross-sectional online survey that included 281 PwMS from Argentina was conducted. Screening instruments: Demographics and clinical data, health-related QoL (MS Impact Scale-29), Fatigue Severity Scale, The Hospital Anxiety and Depression Scale, sleep disorders, physical disability (self-administrated Expanded Disability Status Scale) and medical or recreational cannabis use were evaluated. A logistic regression model was carried out.

Results: Current users (cannabis was used within the past year) was reported in 34.2% and former users (had tried cannabis but not used it within the past year) in 22.7%. Daily cannabis use was reported in 31.3% (current + former users) of the studied cohort, 41.9% started their use after MS diagnosis and 54.3% of them had never discussed about cannabis use with their neurologist. Recreational use was reported in 47.5%. Younger (age below 30 years) PwMS (OR = 2.39, p = 0.03), presence of chronic pain (OR = 2.42, p = 0.002) and current alcohol intake (OR = 3.33, p = 0.001) were predictors of current cannabis use in our multivariate model.

Conclusion: A high prevalence of use of cannabis in PwMS from Argentina was observed. Demographic, symptoms and lifestyle factors predict cannabis use. Identifying the presence and severity of these conditions would contribute to a better MS management and treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msard.2021.102932DOI Listing
June 2021

An Abnormally High Neutrophil-to-Lymphocyte Ratio Is Not an Independent Outcome Predictor in AQP4-IgG-Positive NMOSD.

Front Immunol 2021 23;12:628024. Epub 2021 Feb 23.

Centro de Esclerosis Múltiple de Buenos Aires (CEMBA), Buenos Aires, Argentina.

Background: The neutrophil-to-lymphocyte ratio (NLR) has been investigated in many autoimmune conditions as a biomarker of inflammation and/or disease activity. The role of NLR in AQP4-IgG-positive neuromyelitis optica spectrum disorders (NMOSD) is far from clear. In this study, NLR was evaluated in patients with AQP4-IgG-positive NMOSD at disease onset and its prognostic impact was subsequently assessed.

Methods: In this multicenter study, we retrospectively included all recent/newly diagnosed treatment-naïve patients with AQP4-IgG-positive NMOSD (n=90) from three different countries in Latin America (LATAM): Argentina, Ecuador, and Mexico. NLR was compared between AQP4-IgG-positive NMOSD and healthy controls (HC, n = 365). Demographic, clinical, paraclinical (including imaging), and prognostic data at 12 and 24 months were also evaluated. Multivariate regression analysis was used to describe and identify independent associations between the log-transformed NLR and clinical (relapses and EDSS) and imaging (new/enlarging and/or contrast-enhancing MRI lesions) outcomes.

Results: NLR was higher in NMOSD patients during the first attack compared with HC (2.9 ± 1.6 vs 1.8 ± 0.6; p<0.0001). Regardless of immunosuppressant's initiation at disease onset, NLR remained higher in NMOSD patients at 12 (2.8 ± 1.3; p<0.0001) and 24 (3.1 ± 1.6; p<0.0001) months. No association was found at 12 and 24 months between the log-transformed NLR and the presence of relapses, new/enlarging and/or contrast-enhancing MRI lesions, and/or physical disability.

Conclusions: In this cohort of LATAM patients with AQP4-IgG-positive NMOSD, NLR was abnormally high in attacks but also during follow-up. However, a high NLR was not an independent predictor of clinical or imaging outcomes in our models.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.628024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7950315PMC
February 2021

Radiologically isolated syndrome: from biological bases to practical management.

Neurol Sci 2021 Apr 25;42(4):1335-1344. Epub 2021 Jan 25.

Clínica de Esclerosis Múltiple, Hospital Ramos Mejía, Buenos Aires, Argentina.

Background: Technological advances and greater availability of magnetic resonance imaging have prompted an increment on incidental and unexpected findings within the central nervous system. The concept of radiologically isolated syndrome characterizes a group of subjects with images suggestive of demyelinating disease in the absence of a clinical episode compatible with multiple sclerosis. Since the description of this entity, many questions have arisen; some have received responses but others remain unanswered. A panel of experts met with the objective of performing a critical review of the currently available evidence. Definition, prevalence, biological bases, published evidence, and implications on patient management were reviewed. Thirty to 50% of subjects with radiologically isolated syndrome will progress to multiple sclerosis in 5 years. Male sex, age < 37 years old, and spinal lesions increase the risk. These subjects should be evaluated by a multiple sclerosis specialist, carefully excluding alternative diagnosis. An initial evaluation should include a brain and complete spine magnetic resonance, visual evoked potentials, and identification of oligoclonal bands in cerebrospinal fluid. Disease-modifying therapies could be considered when oligoclonal bands or radiological progression is present.

Conclusion: At present time, radiologically isolated syndrome cannot be considered a part of the multiple sclerosis spectrum. However, a proportion of patients may evolve to multiple sclerosis, meaning it represents much more than just a radiological finding.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10072-021-05069-6DOI Listing
April 2021

What percentage of AQP4-ab-negative NMOSD patients are MOG-ab positive? A study from the Argentinean multiple sclerosis registry (RelevarEM).

Mult Scler Relat Disord 2021 Apr 7;49:102742. Epub 2021 Jan 7.

Hospital Central de Mendoza, Mendoza.

Background: Myelin oligodendrocyte glycoprotein antibodies (MOG-ab) have been described in aquaporin-4-antibodies(AQP4-ab)-negative neuromyelitis optica spectrum disorder (NMOSD) patients. We aimed to evaluate the percentage of AQP4-ab-negative NMOSD patients who are positive for MOG-ab in a cohort of Argentinean patients included in RelevarEM (Clinical Trials registry number NCT03375177).

Methods: RelevarEM is a longitudinal, strictly observational multiple sclerosis (MS) and NMOSD registry in Argentina. Of 3031 consecutive patients (until March 2020), 165 patients with phenotype of suspected NMOSD, whose relevant data for the purpose of this study were available, were included. Data on demographic, clinical, paraclinical and treatment in AQP4-ab (positive, negative and unknown) and MOG-ab (positive and negative) patients were evaluated.

Results: A total of 165 patients (79 AQP4-Ab positive, 67 AQP4-Ab negative and 19 unknown) were included. Of these, 155 patients fulfilled the 2015 NMOSD diagnostic criteria. Of 67 AQP4-Ab-negative patients, 36 (53.7%) were tested for MOG-Ab and 10 of them (27.7%) tested positive. Serum AQP4-ab levels were tested by means of cell-based assay (CBA) in 48 (35.2%), based on tissue-based indirect immunofluorescence assays in 58 (42.6%) and enzyme-linked immunosorbent assay in 4 (2.9%). All MOG-ab were tested by CBA. Optic neuritis (90%) was the most frequent symptom at presentation and optic nerve lesions the most frequent finding (80%) in neuroimaging of MOG-ab-associated disease. Of these, six (60%) patients were under immunosuppressant treatments at latest follow-up.

Conclusion: We observed that 27.7% (10/36) of the AQP4-ab-negative patients tested for MOG-ab were positive for this antibody, in line with results from other world regions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msard.2021.102742DOI Listing
April 2021

Time interval between disease onset and MS diagnosis during the last decades in Latin America.

Mult Scler Relat Disord 2021 Feb 10;48:102672. Epub 2020 Dec 10.

Department of Neurology, Fleni, Buenos Aires, Argentina.

The objective was to evaluate the interval from first symptom of multiple sclerosis (MS) to diagnosis with the introduction of MS diagnostic criteria in a Latin American (LATAM) population.

Methods: Patients with relapsing-remitting MS (RRMS) completed a survey in 12 LATAM countries. Date of disease onset (first relapse) and date of diagnosis (confirmed disease) were required. Survival probabilities were evaluated for 5 diagnosis epoch groups: group 1: 1983-2000 Poser; group 2: 2001-2004 McDonald's first version; group 3: 2005-2009 revisions of 2005; group 4: 2010-2016 revisions of 2010; and group 5: 2017-2019 revisions of 2017.

Results: 1188 (75.6% females) patients were included. Mean time from disease onset to diagnosis in group 1 was 21 ± 8 months; in group 2, 19 ± 7 months; in group 3, 16 ± 10 months; in group 4, 9.6 ± 8.5 months; and in group 5, 8.2 ± 10 months. Significant differences were observed between groups 1, 2, 3 vs. 4 and 5 (p<0.001), while no differences were observed between groups 4 and 5 (p=0.08).

Conclusion: We observed a significant shortening of time from MS onset to diagnosis with the adoption of new diagnostic criteria in LATAM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msard.2020.102672DOI Listing
February 2021

Absence of latitudinal gradient in oligoclonal bands prevalence in Argentina.

Mult Scler Relat Disord 2020 Nov 13;46:102582. Epub 2020 Oct 13.

Servicio de Neurología - Hospital San Bernardo, Salta, Argentina.

Background: Like MS prevalence, oligoclonal bands (OCB) frequency seems to follow a latitudinal gradient. Argentina is extensive, latitude-wise, and previous studies have not found an MS prevalence latitudinal gradient. Our aim is to describe OCB prevalence in MS, clinically isolated syndrome (CIS) and radiologically isolated syndrome (RIS) patients included in the Argentinean MS and NMOSD registry (RelevarEM) and to investigate if it follows a latitudinal gradient.

Methods: For each province, an average latitude was calculated, and OCB frequency was investigated. Multivariate logistical regression analysis and linear correlation were performed. Statistical analysis was repeated after excluding patients from centers using isoelectric focusing (IEF) in less than 95% of patients (CwIEF<95).

Results: We included 2866 patients. OCB where positive in 73.9% of patients. No association or correlation were found between OCB and latitude of residence, even after excluding patients from (CwIEF<95).

Conclusion: OCB positivity does not follow a latitudinal gradient in Argentina. Also, OCB positivity is lower than described in other world regions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msard.2020.102582DOI Listing
November 2020

Usage trend of oral drugs for multiple sclerosis patients in Argentina.

Mult Scler Relat Disord 2021 Jan 2;47:102664. Epub 2020 Dec 2.

Centro Universitario de Esclerosis Múltiple, Hospital JM Ramos Mejía. Electronic address:

Introduction: Over the past decade, numerous disease modifying drugs (DMDs) for relapsing- remitting multiple sclerosis (RRMS) have been approved in Argentina. The use of oral DMDs (oDMDs) has increased in recent years, although real-life data in our region is limited. We aimed to describe the tendency in the use of oDMDs (as first treatment option or after switch) in relationship with their approval in Argentina.

Methods: A retrospective study in a cohort of MS patients from five Argentinian MS centers was conducted. Regarding the availability of different oDMDs in Argentina, we define three periods (P1-3): P1: 2012 - 2014; P2: 2015 - 2017 and P3: 2018 - 2020. An analysis was performed comparing between these three periods to assess the tendency for oDMDs use over time.

Result: The most frequently prescribed treatment as first DMD was: interferon beta 1a (40%) in P1, fingolimod (37.3%) in P2 and also fingolimod (35%) in P3. We found an increase in the use of oDMTs as initial treatment over time (P1: 17.7%, P2: 63.9% and P3: 65.0%; Chi-square = 41.9 p <0.01). We also found a tendency to increase the use of oDMTs after a first switch (P1: 45.5%, P2: 60.1% and P3 78.3%). Multivariate analysis showed that disease evolution (OR=1.06, p=0.04), and year of treatment initiation (OR=1.01 p<0.01) were independently associated with choice of oDMTs.

Conclusion: This study identified an increasing tendency for the use of oDMDs as initial treatment of RMS in relationship with their approval in Argentina.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msard.2020.102664DOI Listing
January 2021

Spinal cord and brain MRI should be routinely performed during follow-up in patients with NMOSD - Yes.

Mult Scler 2021 01 3;27(1):13-15. Epub 2020 Nov 3.

Department of Neurology, FLENI, Buenos Aires, Argentina.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1352458520960804DOI Listing
January 2021

Coping strategies used by patients with relapsing multiple sclerosis from Argentina: correlation with quality of life and clinical features.

Neurol Res 2021 Feb 10;43(2):126-132. Epub 2020 Oct 10.

Neuroimmunology Unit, Department of Neuroscience, Hospital Alemán , Buenos Aires, Argentina.

Background: Multiple sclerosis (MS) is a chronic neurodegenerative and inflammatory disease. The adaptation to MS depends on the effectiveness of coping, which moderates the process of adaptation and psychological well-being.

Objectives: We aimed to analyze the coping strategies of an Argentinean population of patients with MS (PwMS) and their association with clinical variables and health-related quality of life (QoL).

Methods: A nationwide cross-sectional study. Screening instruments: Demographics and clinical data, coping strategies (Brief Coping Orientation to Problems Experienced, [COPE-28]), health-related QoL (MS Impact Scale, [MSIS-29]), Fatigue Severity Scale, and physical disability (self-administrated Expanded Disability Status Scale, [EDSS]).

Results: We included 249 PwMS. Most responders were female (74.7%) with a mean age at survey of 38.6 (±10.7) and had a MS duration of 7.3 years (range: 1-43 years) and a mean EDSS of 1.9 (±1.8). Younger age (r = -0.17), active MS (r = 0.25), higher fatigue (r = 0.22), MSIS-29 total (r = 0.34), MSIS-physical (r = 0.26), MSIS-psychological scores (r = 0.44), higher scores for perception of both severity of MS (r = 0.12) and wheelchair-dependency (r = 0.14) correlated significantly with the use of maladaptive coping strategies. However, active MS (β2.10, p = 0.01), MSIS-psychological score (β0.28, p < 0.0001), high education level (β - 1.15, p = 0.04), and EDSS (β - 0.84, p = 0.0001) were independent predictors of the utilization of maladaptive coping strategies after having applied multivariate analysis via linear regression.

Conclusions: Maladaptive coping strategies used by PwMS are associated with relevant clinical aspects of the disease and with worse health-related QoL scores.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/01616412.2020.1831304DOI Listing
February 2021

Acute optic nerve lesions in first-ever NMOSD-related optic neuritis using conventional brain MRI: A Latin American multicenter study.

Mult Scler Relat Disord 2020 Nov 2;46:102558. Epub 2020 Oct 2.

Centro de Esclerosis Múltiple de Buenos Aires (CEMBA), Buenos Aires, Argentina.

Background: Few studies regarding MRI-defined acute optic nerve lesions (aONL) in patients with first-ever neuromyelitis optica spectrum disorder (NMOSD)-related optic neuritis (ON) have been reported worldwide and none of them was conducted in Latin America (LATAM). Therefore, we aimed to assess the frequency of aONL at disease onset using conventional brain MRI in LATAM.

Methods: We reviewed the medical records and brain MRIs (≤30 days from ON onset) of patients with ON as first lifetime NMOSD attack. Patients from Argentina (n=48), Ecuador (n=24), Brazil (n=22), Venezuela (n=10) and Mexico (n=8) were included, and further divided into two subgroups according to either presence (P-MRI) or absence (A-MRI) of aONL (T2 hyperintensity and/or contrast enhancement). Clinical, paraclinical, imaging and prognostic data were compared.

Results: A total of 112 patients were included and aONL were found in 86 (76.7%) at disease onset. Aquaporin-4 antibodies were detected in 69.6%. Non-Caucasian patients comprised 59.8% of the total cohort. In P-MRI, conventional brain MRI showed isolated or combined unilateral (54.4%, [8.5% of these aONL were associated with chiasmatic lesions]) and bilateral (46.6%, [35.9% of these aONL were associated with chiasmatic lesions]) lesions. Thus, 100% of chiasmatic lesions were associated with unilateral or bilateral lesions. No statistically significant differences were found in age, gender, ethnicity, clinical course, mean follow-up time, disability, and spinal cord MRI findings. However, rituximab use was higher in P-MRI than in A-MRI (p=0.006).

Conclusions: More than three quarters of LATAM patients with first-ever NMOSD-related ON have aONL detected by brain MRI. Unilateral lesions were the most common finding. Further studies including different ethnicities are needed to assess the generalizability of our results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msard.2020.102558DOI Listing
November 2020

Bruton's tyrosine kinase inhibitors: a promising emerging treatment option for multiple sclerosis.

Expert Opin Emerg Drugs 2020 12 21;25(4):377-381. Epub 2020 Sep 21.

Department of Neurology, Fleni , Buenos Aires, Argentina.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14728214.2020.1822817DOI Listing
December 2020

Clinical and demographic characteristics of primary progressive multiple sclerosis in Argentina: Argentinean registry cohort study (RelevarEM).

Neurol Sci 2020 Nov 25;41(11):3329-3335. Epub 2020 Aug 25.

Sinapsis, Centro Neurológico, La Pampa, Argentina.

Background: Primary progressive multiple sclerosis (PPMS) is an infrequent clinical form of multiple sclerosis (MS). Scarce information is available about PPMS in Latin America. The aim of this work is to describe the clinical and demographic characteristics of PPMS patients in Argentina.

Material And Methods: RelevarEM is a longitudinal, strictly observational registry in Argentina. Clinical and epidemiological data from PPMS patients were described.

Results: There were 144 cases of PPMS. They represented 7% of MS patients. The mean age was 44.1 years. The female:male ratio was 1.08. The mean Expanded Disability Status Scale (EDSS) score was 5.5 and the mean disease evolution time was 10.6 years. Oligoclonal bands were found in 72.9%. At the time of diagnosis, magnetic resonance imaging showed spinal cord lesions in 82.6% and contrast-enhancing brain lesions in 18.1% of patients. Almost one third of patients were treated with a disease-modifying drug, and ocrelizumab was the most frequently used (55.8%).

Conclusions: PPMS is an infrequent subtype of MS and its recognition is of the highest importance as it has its own evolution, treatment, and prognosis. The importance of our research resides in providing local data and contributing to a better understanding of PPMS and its treatment in Latin America.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10072-020-04680-3DOI Listing
November 2020

Latin American consensus recommendations for management and treatment of neuromyelitis optica spectrum disorders in clinical practice.

Mult Scler Relat Disord 2020 Oct 29;45:102428. Epub 2020 Jul 29.

Department of Neurology, Fleni, Buenos Aires, Argentina. Electronic address:

Background: During the last two decades, neuromyelitis optica spectrum disorder (NMOSD) has undergone important changes, with new diagnostic markers and criteria, better recognition of clinical phenotypes, better disease prognosis and new therapeutic approaches. Consequently, management of NMOSD patients in Latin American (LATAM) has become more complex and challenging in clinical practice. In making these consensus recommendations, the aim was to review how the disease should be managed and treated among LATAM patients, in order to improve long-term outcomes in these populations.

Methods: A panel of LATAM neurologists who are experts in demyelinating diseases and dedicated to management and care of NMOSD patients gathered virtually during 2019 and 2020 to make consensus recommendations on management and treatment of NMOSD patients in LATAM. To achieve this consensus, the RAND/UCLA methodology for reaching formal consensus was used.

Results: The recommendations focused on diagnosis and differential diagnoses, disease prognosis, tailored treatment, identification of suboptimal treatment response and special circumstances management. They were based on published evidence and expert opinions.

Conclusions: The recommendations of these consensus guidelines seek to optimize management and specific treatment of NMOSD patients in LATAM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msard.2020.102428DOI Listing
October 2020

Decision-making on management of ms and nmosd patients during the COVID-19 pandemic: A latin american survey.

Mult Scler Relat Disord 2020 Sep 20;44:102310. Epub 2020 Jun 20.

Centro de Esclerosis Múltiple de Buenos Aires (CEMBA), CABA, Argentina.

Background: The emergence of COVID-19 and its vertiginous spreading speed represents a unique challenge to neurologists managing multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). The need for data on the impact of the virus on these patients grows rapidly. There is an urgent necessity of sharing information to enable evidence-based decision making on the clinical management. There are no data on what physicians are doing on clinical practice in Latin American countries.

Aim: to investigate current management opinion of Latin American MS and/or NMOSD expert neurologists based on their experience and recommendations.

Methods: we developed a voluntary web-based survey based on hypothetical situations that these patients may encounter, while taking into account the potential risk of developing severe COVID-19 infection.

Results: 60% of the experts had the possibility of monitoring their patients by telemedicine. Most neurologists postpone magnetic resonance. Laboratory blood tests delay is associated with the type of treatment. Platform therapies, dimethyl-fumarate and natalizumab are considered safe options to initiate in naive patients.

Conclusion: decision-making about MS and NMOSD patients has become even more complex in order to adapt to the COVID-19 pandemic. Risks and benefits should be taken into consideration throughout the patient follow-up.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msard.2020.102310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837246PMC
September 2020

Diagnostic uncertainty during the transition to secondary progressive multiple sclerosis: Multicenter study in Argentina.

Mult Scler 2021 04 2;27(4):579-584. Epub 2020 Jun 2.

Centro de Esclerosis Múltiple de Buenos Aires, Buenos Aires, Argentina.

Background: A period of diagnostic uncertainty often characterizes the clinical transition from relapsing to secondary progressive multiple sclerosis (SPMS).

Objective: The aim of this study was to describe the length of time required to reclassify relapsing-remitting MS (RRMS) patients who have clinically transitioned to SPMS (diagnosis uncertainty).

Methods: This is a retrospective multicenter cohort study conducted in Argentina, identifying in every center all patients with diagnosis of MS who transitioned from RRMS to SPMS during the follow-up. We identified the dates of the last definitive RRMS and first definitive SPMS diagnoses for diagnostic uncertainty. The time required to reclassify RRMS who transitioned to SPMS and the time from disease onset to reclassify SPMS were calculated using the Kaplan-Meier method.

Results: A total of 170 patients were included, where the mean age at disease onset (first symptom) was 36 ± 6 years; the length of time required to reclassify RRMS patients who transitioned to SPMS was 3.3 ± 1.1 years (range = 1-7 years); and the time from disease onset to classify SPMS was 19.4 ± 8.5 years (range = 16-35 years).

Conclusion: A period of diagnostic uncertainty regarding the transition from RRMS to SPMS was present in many of our patients, with a mean time of 3.3 years.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1352458520924586DOI Listing
April 2021

Consensus recommendations for family planning and pregnancy in multiple sclerosis in argentina.

Mult Scler Relat Disord 2020 Aug 4;43:102147. Epub 2020 May 4.

Instituto Lennox/Clínica Reina Fabiola, Córdoba, Argentina.

Background: Multiple sclerosis (MS) is the most common chronic immune-mediated neurological disorder in young adults, more frequently found in women than in men. Therefore, pregnancy-related issues have become an object of concern for MS professionals and patients. The aim of this work was to review the existing data to develop the first Argentine consensus for family planning and pregnancy in MS patients.

Methods: A panel of expert neurologists from Argentina engaged in the diagnosis and care of MS patients met both virtually and in person during 2019 to carry out a consensus recommendation for family planning and pregnancy in MS. To achieve consensus, the procedure of the "formal consensus-RAND/UCLA method" was used.

Results: Recommendations were established based on published evidence and expert opinion focusing on pre-pregnancy counseling, pregnancy, and postpartum issues.

Conclusion: The recommendations of these consensus guidelines are intended to optimize the management and treatment of MS patients during their reproductive age in Argentina.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msard.2020.102147DOI Listing
August 2020