Publications by authors named "Edgardo Cristiano"

96 Publications

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

Mult Scler Relat Disord 2021 Mar 7;51:102886. Epub 2021 Mar 7.

Centro de esclerosis múltiple de Buenos Aires, Argentina; Servicio de Neurología, Hospital Universitario de CEMIC, Buenos Aires, Argentina.

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.
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http://dx.doi.org/10.1016/j.msard.2021.102886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937038PMC
March 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.
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http://dx.doi.org/10.3389/fimmu.2021.628024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7950315PMC
February 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 Jan 7;49:102742. Epub 2021 Jan 7.

Sección de Neuroinmunología y Enfermedades Desmielinizantes, Servicio de Neurología - Hospital de Clínicas José de San Martín, CABA; Servicio de Neurología, Hospital Universitario de CEMIC, CABA.

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

Effect of Disease-Modifying Therapy on Disability in Relapsing-Remitting Multiple Sclerosis Over 15 Years.

Neurology 2021 02 28;96(5):e783-e797. Epub 2020 Dec 28.

From CORe (T.K., I.D., S.S., C.M.), Department of Medicine, University of Melbourne; MS Centre (T.K., I.D., S.S., C.M.), Department of Neurology, Royal Melbourne Hospital, Australia; Karolinska Institute (T.S.), Stockholm, Sweden; Department of Neuroscience (T.S., V.J., A.v.d.W., O.S., H.B.), Central Clinical School, Monash University, Melbourne; Burnet Institute (T.S.), Melbourne, Australia; Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), General University Hospital and Charles University in Prague, Czech Republic; Department of Basic Medical Sciences, Neuroscience and Sense Organs (M. Trojano), University of Bari, Italy; Hospital Universitario Virgen Macarena (G.I.), Sevilla, Spain; Department of Neuroscience, Imaging and Clinical Sciences (A.L.), University "G. d'Annunzio," Chieti; Department of Biomedical and Neuromotor Sciences (A.L.), University of Bologna, IRCCS Istituto delle Scienze Neurologiche di Bologna, Italy; Hopital Notre Dame (A.P., M.G., P.D.), Montreal; CHUM and Universite de Montreal (A.P., M.G., P.D.); CISSS Chaudière-Appalache (P.G.), Levis, Canada; Department of Neurology (V.J., A.v.d.W., O.S., H.B.), Alfred Hospital, Melbourne, Australia; Neuro Rive-Sud (F. Grand'Maison), Quebec, Canada; Department of Neuroscience (P.S., D.F.), Azienda Ospedaliera Universitaria, Modena, Italy; Isfahan University of Medical Sciences (V.S.), Isfahan, Iran; Amiri Hospital (R. Alroughani), Kuwait City, Kuwait; Zuyderland Ziekenhuis (R.H.), Sittard, the Netherlands; Medical Faculty (M. Terzi), 19 Mayis University, Samsun; KTU Medical Faculty Farabi Hospital (C.B.), Karadeniz Technical University, Trabzon, Turkey; School of Medicine and Public Health (J.L.-S.), University Newcastle; Department of Neurology (J.L.-S.), John Hunter Hospital, Newcastle, Australia; UOC Neurologia (E.P.), Azienda Sanitaria Unica Regionale Marche-AV3, Macerata, Italy; Cliniques Universitaires Saint-Luc (V.V.P.), Brussels, Belgium; University of Parma (F. Granella); C. Mondino National Neurological Institute (R.B.), Pavia; Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino (D.S.), Italy; Flinders University (M. Slee), Adelaide; Westmead Hospital (S.V.), Sydney, Australia; Nemocnice Jihlava (R. Ampapa), Czech Republic; University of Queensland (P.M.), Brisbane; Royal Brisbane and Women's Hospital (P.M.), Brisbane, Australia; Hospital Germans Trias i Pujol (C.R.-T.), Badalona, Spain; CSSS Saint-Jérôme (J.P.), Canada; Hospital Universitario Donostia (J.O.), Paseo de Begiristain, San Sebastián, Spain; Hospital Italiano (E.C.), Buenos Aires, Argentina; Brain and Mind Centre (M.B.), University of Sydney, Australia; INEBA-Institute of Neuroscience Buenos Aires (M.L.S.), Argentina; Hospital de Galdakao-Usansolo (J.L.S.-M.), Galdakao, Spain; Liverpool Hospital (S. Hodgkinson), Sydney, Australia; Jahn Ferenc Teaching Hospital (C.R.), Budapest, Hungary; Craigavon Area Hospital (S. Hughes), UK; Jewish General Hospital (F.M.), Montreal, Canada; Deakin University (C.S.), Geelong; Monash Medical Centre (E.B.), Melbourne, Australia; South East Trust (O.G.), Belfast, UK; Perron Institute (A.K.), University of Western Australia, Nedlands; Institute of Immunology and Infectious Diseases (A.K.), Murdoch University; Sir Charles Gairdner Hospital (A.K.), Perth, Australia; Department of Neurology (T.C.), Faculty of Medicine, University of Debrecen, Hungary; Bombay Hospital Institute of Medical Sciences (B.S.), Mumbai, India; St Vincents Hospital (N.S.), Fitzroy, Melbourne, Australia; Veszprém Megyei Csolnoky Ferenc Kórház zrt (I.P.), Veszprem, Hungary; Royal Hobart Hospital (B.T.), Australia; Semmelweis University Budapest (M. Simo), Hungary; Central Military Emergency University Hospital (C.-A.S.), Bucharest; Titu Maiorescu University (C.-A.S.), Bucharest, Romania; BAZ County Hospital (A.S.), Miskolc, Hungary; and Box Hill Hospital (H.B.), Melbourne, Australia.

Objective: To test the hypothesis that immunotherapy prevents long-term disability in relapsing-remitting multiple sclerosis (MS), we modeled disability outcomes in 14,717 patients.

Methods: We studied patients from MSBase followed for ≥1 year, with ≥3 visits, ≥1 visit per year, and exposed to MS therapy, and a subset of patients with ≥15-year follow-up. Marginal structural models were used to compare the cumulative hazards of 12-month confirmed increase and decrease in disability, Expanded Disability Status Scale (EDSS) step 6, and the incidence of relapses between treated and untreated periods. Marginal structural models were continuously readjusted for patient age, sex, pregnancy, date, disease course, time from first symptom, prior relapse history, disability, and MRI activity.

Results: A total of 14,717 patients were studied. During the treated periods, patients were less likely to experience relapses (hazard ratio 0.60, 95% confidence interval [CI] 0.43-0.82, = 0.0016), worsening of disability (0.56, 0.38-0.82, = 0.0026), and progress to EDSS step 6 (0.33, 0.19-0.59, = 0.00019). Among 1,085 patients with ≥15-year follow-up, the treated patients were less likely to experience relapses (0.59, 0.50-0.70, = 10) and worsening of disability (0.81, 0.67-0.99, = 0.043).

Conclusion: Continued treatment with MS immunotherapies reduces disability accrual by 19%-44% (95% CI 1%-62%), the risk of need of a walking aid by 67% (95% CI 41%-81%), and the frequency of relapses by 40-41% (95% CI 18%-57%) over 15 years. This study provides evidence that disease-modifying therapies are effective in improving disability outcomes in relapsing-remitting MS over the long term.

Classification Of Evidence: This study provides Class IV evidence that, for patients with relapsing-remitting MS, long-term exposure to immunotherapy prevents neurologic disability.
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http://dx.doi.org/10.1212/WNL.0000000000011242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884998PMC
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.

Neuroimmunology Unit - FLENI, Montañeses 2325, CABA, 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.
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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.
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http://dx.doi.org/10.1016/j.msard.2020.102664DOI Listing
January 2021

[Clinical and demographic aspects of secondary progressive multiple sclerosis in Argentina].

Medicina (B Aires) 2020 ;80(6):606-610

Centro de Esclerosis Múltiple de Buenos Aires, Argentina.

The objective of the study was to describe the clinical and demographic aspects of patients with secondary progressive multiple sclerosis (SPMS) included in the Argentine MS Registry (RelevarEM, Clinical Trials registry number 03375177). RelevarEM is a longitudinal, strictly observational registry of patients with MS and neuromyelitis optica spectrum disorders. Clinical and demographic aspects were described in patients with SPMS and compared with relapsing remitting MS patients (RRMS). A total of 1723 patients with MS were included (1605, 93.2% RRMS and 118, 6.8%, SPMS). In SPMS, the median age was 53 (inter quartile range [IQR] 47-62) years, 67% were women, median disease duration of 19.5 (IQR 14-26) years, median EDSS (expanded disability status scale) 6.5 and 48.3% were under treatment for their MS. Only 23.7% of patients with SPMS were actively working and 86% had a disability certificate; 35.6% of patients with SPMS presented new lesions in MRI and 5% had clinical relapses during the past 12 months of the registry entry showing a significantly lower disease activity compared with RRMS (p < 0.01).
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December 2020

High birth weight and risk of multiple sclerosis: A multicentre study in Argentina.

Mult Scler Relat Disord 2021 Jan 12;47:102628. Epub 2020 Nov 12.

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

Background: Multiple sclerosis (MS) is now recognized as a multifactorial disease in which genetic and environmental factors intervene. Considerable efforts have been made to identify external risk factors present in childhood, adolescence and youth, though only a few perinatal risk factors have been positively associated with MS. Previously, we found an association between high birth weight and MS in male patients in a small study in Argentina. The present research was designed to further assess the association between high birth weight and MS in a larger sample of patients, using an extensive and validated general population database as control.

Methods: We present an analytical observational, multicentre, population-based, and case-control study. A total of 637 patients (cases) with confirmed MS diagnosis attending five MS specialized centres in Argentina were included. Birth weight (BW) data was recalled by the patient's mother, which is a validated approach. A two-way comparison was performed. First, we used the standard categories of high, adequate and low BW in grams. Then, we applied the weight percentile distribution to provide reproducible results for further research. For a proper assessment and comparison of variables, we adopted the guidelines of the American Academy of Pediatrics for neonate classification according to gestational weeks and to BW in grams. The neonate's BW distribution of the general population was used as control. For the purposes of the study, we adapted Urquía's et al. curves, which are based on an extensive database of all the live births registered in the country from 2003 to 2007. To measure the magnitude of the proportional differences between low, adequate and high BW, the odds ratio (OR) and their 95% confidence interval (CI) were estimated. The mean BW and percentile values for each sex were compared using a z-Normal test. The respective MS patients and general population BW distribution curves by sex were compared between each other.

Results: Cases and controls were comparable in their demographic, geographic and environmental characteristics. Males showed higher BW than females both in the MS patients and the general population groups. When we applied the sex stratified analysis separately, we found that males in the MS group showed an almost seven times higher risk of high birth weight than males from the general population (OR 6.58 [95% CI 4.81-8.99]). Female patients showed an almost five times higher risk of high BW than their respective controls (OR 4.5 [95% CI 3.06-6.58]). The comparison based on the BW percentile distribution confirmed that MS patients showed higher BW than the general population. This result reached statistical significance from the 75 percentile onwards for both sexes.

Conclusion: In summary, our findings suggested that high BW could be one of the earliest risk factors for MS in life. If this results were reproduced in other centres, high birth weight would emerge as a novel and very early risk factor, potentially modifiable in utero or immediately postpartum, representing a unique opportunity to prevent the disease in future generations.
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http://dx.doi.org/10.1016/j.msard.2020.102628DOI Listing
January 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.
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http://dx.doi.org/10.1016/j.msard.2020.102558DOI Listing
November 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.

Centro Universitario de Esclerosis Múltiple, Hospital Dr. J. M. Ramos Mejía, Facultad de Medicina-UBA, Urquiza 609, C1221ADC, Buenos Aires City, 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.
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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.
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http://dx.doi.org/10.1016/j.msard.2020.102428DOI Listing
October 2020

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

Mult Scler 2021 Apr 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.
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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.

Hospital Italiano de Buenos Aires, 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.
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http://dx.doi.org/10.1016/j.msard.2020.102147DOI Listing
August 2020

Early clinical markers of aggressive multiple sclerosis.

Brain 2020 05;143(5):1400-1413

CORe Unit, Department of Medicine, University of Melbourne, Melbourne, Australia.

Patients with the 'aggressive' form of multiple sclerosis accrue disability at an accelerated rate, typically reaching Expanded Disability Status Score (EDSS) ≥ 6 within 10 years of symptom onset. Several clinicodemographic factors have been associated with aggressive multiple sclerosis, but less research has focused on clinical markers that are present in the first year of disease. The development of early predictive models of aggressive multiple sclerosis is essential to optimize treatment in this multiple sclerosis subtype. We evaluated whether patients who will develop aggressive multiple sclerosis can be identified based on early clinical markers. We then replicated this analysis in an independent cohort. Patient data were obtained from the MSBase observational study. Inclusion criteria were (i) first recorded disability score (EDSS) within 12 months of symptom onset; (ii) at least two recorded EDSS scores; and (iii) at least 10 years of observation time, based on time of last recorded EDSS score. Patients were classified as having 'aggressive multiple sclerosis' if all of the following criteria were met: (i) EDSS ≥ 6 reached within 10 years of symptom onset; (ii) EDSS ≥ 6 confirmed and sustained over ≥6 months; and (iii) EDSS ≥ 6 sustained until the end of follow-up. Clinical predictors included patient variables (sex, age at onset, baseline EDSS, disease duration at first visit) and recorded relapses in the first 12 months since disease onset (count, pyramidal signs, bowel-bladder symptoms, cerebellar signs, incomplete relapse recovery, steroid administration, hospitalization). Predictors were evaluated using Bayesian model averaging. Independent validation was performed using data from the Swedish Multiple Sclerosis Registry. Of the 2403 patients identified, 145 were classified as having aggressive multiple sclerosis (6%). Bayesian model averaging identified three statistical predictors: age > 35 at symptom onset, EDSS ≥ 3 in the first year, and the presence of pyramidal signs in the first year. This model significantly predicted aggressive multiple sclerosis [area under the curve (AUC) = 0.80, 95% confidence intervals (CIs): 0.75, 0.84, positive predictive value = 0.15, negative predictive value = 0.98]. The presence of all three signs was strongly predictive, with 32% of such patients meeting aggressive disease criteria. The absence of all three signs was associated with a 1.4% risk. Of the 556 eligible patients in the Swedish Multiple Sclerosis Registry cohort, 34 (6%) met criteria for aggressive multiple sclerosis. The combination of all three signs was also predictive in this cohort (AUC = 0.75, 95% CIs: 0.66, 0.84, positive predictive value = 0.15, negative predictive value = 0.97). Taken together, these findings suggest that older age at symptom onset, greater disability during the first year, and pyramidal signs in the first year are early indicators of aggressive multiple sclerosis.
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http://dx.doi.org/10.1093/brain/awaa081DOI Listing
May 2020

Brain magnetic resonance imaging features in multiple sclerosis and neuromyelitis optica spectrum disorders patients with or without aquaporin-4 antibody in a Latin American population.

Mult Scler Relat Disord 2020 Jul 14;42:102049. Epub 2020 Mar 14.

Servicio de Neurología, Hospital Italiano de Buenos Aires, Argentina, Gascón 450, Buenos Aires C 1181 Argentina.

Introduction: There is scarce evidence comparing the behavior in magnetic resonance (MRI) between positive and negative aquaporin-4 antibody neuromyelitis optica spectrum disorders (P-NMOSD and NNMOSD, respectively). The aim of this study was to describe and compare MRI features through a quantitative and qualitative analysis between P-NMOSD and NNMOSD patients in a cohort from Latin American (LATAM) patients.

Methods: We retrospectively reviewed the MRI and medical records of NMOSD patients as defined by the 2015 validated diagnostic criteria, and with at least 3 years of follow-up from disease onset (first symptom). We included patients from Argentina, Brazil and Venezuela. To be included, NMOSD patients must have had AQP4-ab status measured by a cell-based assay. Brain MRIs were obtained for each participant at disease onset and every 12 months for 3 years. Demographics, clinical and MRI variables (T2 lesion volume [T2LV], lesion distribution, cortical thickness [CT] and percentage of brain volume loss [PBVL]) were analyzed and compared between groups (P-NMOSD; NNMOSD) at disease onset and follow-up. A multiple sclerosis (MS) control group of patients was also included.

Results: We included 24 P-NMOSD, 15 NNMOSD and 35 MS patients. No differences in age, gender and follow-up time were observed between groups. Nor were differences found in lesion distribution at disease onset or in brain volumes during follow-up between P-NMOSD and NNMOSD patients (T2LV = 0.43, CT = 0.12, PBVL p = 0.45). Significant differences were observed in lesion distribution at disease onset, as well as in brain volumes during follow-up between NMOSD and MS (T2LV = p<0.001, CT = p<0.001, PBVL p = 0.01).

Conclusion: Different MRI features were observed between MS and NMOSD. However, no quantitative nor qualitative differences were observed between P-NMOSD and NNMOSD, not allowing us to differentiate NMOSD conditions by MRI.
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http://dx.doi.org/10.1016/j.msard.2020.102049DOI Listing
July 2020

Differential white and gray matter damage in highly active multiple sclerosis: A prospective cohort study.

J Clin Neurosci 2020 Apr 27;74:65-68. Epub 2020 Jan 27.

Centro de Esclerosis Múltiple de Buenos Aires, Hospital Italiano de Buenos Aires, Argentina. Electronic address:

We analyze the differential brain volume changes in highly active multiple sclerosis (HAMS) vs. non-HAMS patients during the disease onset.

Methods: HAMS was defined as: a) patients with 1 relapse in the previous year and at least 1 T1 gadolinium-enhancing lesion or 9 or more T2 lesions while on therapy with other disease modifying treatment (DMD); or b) patients with 2 or more relapses in the previous year, whether on DMD or not. High-resolution T1 weighted MRI scans were acquired at onset and every 12 months for 2 years. Lesion load and brain volume measurements were determined. At onset, gray matter volume (GMV) and white matter volume (WMV) tissue volumes were calculated using the SIENAX. Longitudinal changes were estimated by using SIENA to calculate the percentage of brain volume loss. Differences between volumes per group at onset and at the end of the follow up were established.

Results: 64 patients, mean age 38.4 years, 35 (57%) women were included. A total of 14 (21%) were classified as HAMS. At onset, HAMS patients showed lower GMV and WMV volume compared with non-HAMS patients (p = 0.003 and p = 0.01, respectively). During the follow up, HAMS patients showed a higher decrease in GM volume compared with non-HAMS patients (-0.61 vs. - 0.77, p < 0.001) independent from new lesion as well as relapse rate activity during follow up.

Conclusion: HAMS increased rates of GMV atrophy over 24 months compared to non-HAMS patients independent from relapse rate and new T2 lesions.
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http://dx.doi.org/10.1016/j.jocn.2020.01.062DOI Listing
April 2020

Multiple sclerosis and neuromyelitis optica spectrum disorders in Argentina: comparing baseline data from the Argentinean MS Registry (RelevarEM).

Neurol Sci 2020 Jun 20;41(6):1513-1519. Epub 2020 Jan 20.

Sanatorio Güemes, CABA, Argentina.

The objective of this study was to describe and compare the baseline epidemiological data of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) patients included in RelevarEM (Clinical Trials registry number NCT03375177).

Methods: RelevarEM is a longitudinal, strictly observational MS and NMOSD registry in Argentina. Epidemiological and comorbidity data from MS and NMOSD patients were described and compared. For comorbidities, the Charlson comorbidity index (CCI) was used to calculate the burden at entry. CCI was stratified in 0 and ≥ 1 and described for the entire cohort.

Results: A total of 1588 and 75 MS and NMOSD patients (respectively) were included. For MS patients, the mean age was 42 ± 7 years, female sex 65.3%, mean EDSS 2, and mean disease duration 8 ± 6 years. In NMOSD, the mean age was 40 ± 7 years, female sex 78.7%, mean disease duration 5 ± 3.5 years, and mean EDSS 2.5. The most frequent MS phenotype was RRMS in 82.4%. In MS, the CCI was 0 in 85.8.2% while ≥ 1 was in 14.2% of patients. Regarding phenotype stratification, CCI ≥ 1 was 3.9% in CIS, 13.5% in RRMS, 28.7% in SPMS, and 17.4% in PPMS (p < 0.001 between groups). In NMOSD, the CCI was 0 in 64% while ≥ 1 was in 36%. The MS/NMOSD ratio found was 21/1.

Conclusions: This is the first analysis of the longitudinal Argentinean registry of MS and NMOSD describing and comparing conditions that contributes to provide reliable real-world data in the country.
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http://dx.doi.org/10.1007/s10072-019-04230-6DOI Listing
June 2020

New MRI lesions and topography at 6 months of treatment initiation and disease activity during follow up in relapsing remitting multiple sclerosis patients.

Neurol Res 2020 Feb 20;42(2):148-152. Epub 2020 Jan 20.

Servicio de Neurología, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.

: The objective of this study was to assess if the presence of new lesions and their topography on the reference MRI have a prognostic value regarding disease activity during the follow up in relapsing remitting multiple sclerosis (RRMS) patients.: Retrospective cohort study that included patients with RRMS who had a reference MRI (performed at 6 months from the onset of a DMT) and radiological and clinical follow up for at least two years. We identified the number of new MRI lesions and their topography at reference MRI and during the follow up. Cox proportional hazards model analysis was used to evaluate the association between new lesions on reference MRI and the appearance of new lesions and/or clinical relapses at 24-month follow-up.: 56 patients were included, 13 (23.2%) showed new lesions in the reference MRI. The presence of new lesions at reference MRI predicted the occurrence of new lesions at month 24 (HR 3.1, CI 95% 2.5-5.8). The number of lesions and the infratentorial topography at reference MRI were associated with an increased risk of new radiological activity during follow up (HR 3.5, IC95% 3.1-6.1 and HR 2.4, IC95% 1.9-2.7 respectively).: New lesions at the reference MRI in terms of number and topography increase the risk of radiological disease activity during the follow up.
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http://dx.doi.org/10.1080/01616412.2019.1710415DOI Listing
February 2020

Clinical features and prognosis of late-onset neuromyelitis optica spectrum disorders in a Latin American cohort.

J Neurol 2020 May 13;267(5):1260-1268. Epub 2020 Jan 13.

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

Background: We aimed to assess the clinical, paraclinical, imaging and prognostic features of patients with late-onset neuromyelitis optica spectrum disorder (LO-NMOSD; ≥ 50 years at disease onset) LO-NMOSD, compared with early onset-NMOSD (EO-NMOSD, ≤ 49 years at disease onset), in Latin American (LATAM).

Methods: We retrospectively reviewed the medical records of patients with NMOSD, as defined using the 2015 validated diagnostic criteria. We included patients from Argentina, Brazil and Venezuela. They were divided into: LO-NMOSD and EO-NMOSD and comparison among the groups were performed.

Results: Among these 140 NMOSD patients, 24 (17.1%) were LO-NMOSD; 64% were positive for aquaporin-4 antibodies; and 41.5% of this population cohort was non-Caucasian. Severe disability [expanded disability status scale (EDSS) ≥ 6] at the last follow-up and presence of comorbidities were significantly associated with LO-NMOSD, compared with EO-NMOSD. LO-NMOSD patients had a shorter median time to EDSS ≥ 4 than EO-NMOSD patients (46 vs. 60 months; log-rank test p = 0.0006). Furthermore, we observed a positive correlation between age at onset and EDSS score at the last follow-up (Spearman r = 0.34, p < 0.0001).

Conclusion: LO-NMOSD patients from LATAM developed early severe disability, compared with EO-NMOSD. Therefore, age at onset could have important implications for the long-term prognosis of NMOSD patients.
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http://dx.doi.org/10.1007/s00415-020-09699-2DOI Listing
May 2020

Do clinical trials for new disease modifying treatments include real world patients with multiple sclerosis?

Mult Scler Relat Disord 2020 Jan 3;39:101931. Epub 2020 Jan 3.

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

We often see that clinical and demographic characteristics of real-world studies (RWS) do not differ from patients included in randomized controlled trials (RCT).

Objective: to compare clinical and demographic aspects of patients included in RCT and RWS that evaluated new disease modifying treatment in multiple sclerosis (MS).

Methods: a systematic non-language-restricted literature search of RCT and RWS that evaluated new disease modifying treatments (natalizumab, alemtuzumab, ocrelizumab, fingolimod, teriflunomide, dimethyl fumarate and cladribine) from January 2005 to January 2019. Demographic and clinical data were extracted, described and compared.

Results: 18 RCT and 73 RWS were included. We found no differences in clinical and demographic aspects between RCT and RWS except in the frequency of naïve patients included in RCT vs. RWS 65.6% (95%CI 52-74) vs. 36.4% (95%CI 21-46), respectively, (p = 0.013) at study entry, as well as for the inclusion of patients that used previous treatment 34.4% (95%CI 22-41) vs. 63.6% (95%CI 53-74) in RCT and RWS, respectively,(p = 0.007) at study entry.

Conclusion: We did not observe significant differences in most clinical and demographic aspects of included patients in RCT and RWS. Studies that include the full spectrum of MS patients followed in clinical practice are needed.
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http://dx.doi.org/10.1016/j.msard.2020.101931DOI Listing
January 2020

Consensus recommendations on the management of multiple sclerosis patients in Argentina.

J Neurol Sci 2020 Feb 2;409:116609. Epub 2019 Dec 2.

Department of Neurology, Institute for Neurological Research Dr Raul Carrea, FLENI, Argentina.

Introduction: During the last 20 years, multiple sclerosis (MS) disease has seen major changes with new diagnostic criteria, a better identification of disease phenotypes, individualization of disease prognosis and the appearance of new therapeutic options in relapsing remitting as well as progressive MS. As a result, the management of MS patients has become more complex and challenging. The objective of these consensus recommendations was to review how the disease should be managed in Argentina to improve long-term outcomes in MS patients.

Methods: A panel of 36 experts in neurology from Argentina, dedicated to the diagnosis and care of MS patients, gathered both virtually and in person during 2018 and 2019 to carry out a consensus recommendation on the management of MS patients in Argentina. To achieve consensus, the methodology of "formal consensus-RAND/UCLA method" was used.

Results: Recommendations focused on diagnosis, disease prognosis, tailored treatment, treatment failure identification and pharmacovigilance process.

Conclusions: The recommendations of these consensus guidelines attempt to optimize the health care and management of patients with MS in Argentina.
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http://dx.doi.org/10.1016/j.jns.2019.116609DOI Listing
February 2020

An asymptomatic new lesion on MRI is a relapse and should be treated accordingly - Yes.

Mult Scler 2019 12 1;25(14):1842-1843. Epub 2019 Nov 1.

Servicio de Neurología, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina; Centro de Esclerosis Múltiple de Buenos Aires, Buenos Aires, Argentina.

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http://dx.doi.org/10.1177/1352458519855723DOI Listing
December 2019

Redefining the Multiple Sclerosis Severity Score (MSSS): The effect of sex and onset phenotype.

Mult Scler 2020 11 31;26(13):1765-1774. Epub 2019 Oct 31.

Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.

Background: The Multiple Sclerosis Severity Score (MSSS) is a widely used measure of the disability progression rate. However, the global MSSS may not be the best basis for comparison between all patient groups.

Objective: We evaluated sex-specific and onset phenotype-specific MSSS matrices to determine if they were more effective than the global MSSS as a basis for comparison within these subsets.

Methods: Using a large international dataset of multiple sclerosis (MS) patient records and the original MSSS algorithm, we constructed global, sex-specific and onset phenotype-specific MSSS matrices. We compared matrices using permutation analysis.

Results: Our final dataset included 30,203 MS cases, with 28.9% males and 6.5% progressive-onset cases. Our global MSSS matrix did not differ from previously published data ( > 0.05). The progressive-onset-specific matrix differed significantly from the relapsing-onset-specific matrix ( < 0.001), with lower MSSS attributed to cases with the same Expanded Disability Status Score (EDSS) and disease duration. When evaluated with a simulation, using an onset-specific MSSS improved statistical power in mixed cohorts. There were no significant differences by sex.

Conclusion: The differences in the disability accrual rate between progressive- and relapsing-onset MS have a significant effect on MSSS. An onset-specific MSSS should be used when comparing the rate of disability progression among progressive-onset cases and for mixed cohorts.
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http://dx.doi.org/10.1177/1352458519881994DOI Listing
November 2020

Risk of secondary progressive multiple sclerosis: A longitudinal study.

Mult Scler 2020 01 9;26(1):79-90. Epub 2019 Aug 9.

CORe, Department of Medicine, The University of Melbourne, Melbourne, VIC, Australia/Department of Neurology, Royal Melbourne Hospital, Melbourne, VIC, Australia/L4 Centre, Melbourne Brain Centre at Royal Melbourne Hospital, Parkville, VIC, Australia.

Background: The risk factors for conversion from relapsing-remitting to secondary progressive multiple sclerosis remain highly contested.

Objective: The aim of this study was to determine the demographic, clinical and paraclinical features that influence the risk of conversion to secondary progressive multiple sclerosis.

Methods: Patients with adult-onset relapsing-remitting multiple sclerosis and at least four recorded disability scores were selected from MSBase, a global observational cohort. The risk of conversion to objectively defined secondary progressive multiple sclerosis was evaluated at multiple time points per patient using multivariable marginal Cox regression models. Sensitivity analyses were performed.

Results: A total of 15,717 patients were included in the primary analysis. Older age (hazard ratio (HR) = 1.02,  < 0.001), longer disease duration (HR = 1.01,  = 0.038), a higher Expanded Disability Status Scale score (HR = 1.30,  < 0.001), more rapid disability trajectory (HR = 2.82,  < 0.001) and greater number of relapses in the previous year (HR = 1.07,  = 0.010) were independently associated with an increased risk of secondary progressive multiple sclerosis. Improving disability (HR = 0.62,  = 0.039) and disease-modifying therapy exposure (HR = 0.71,  = 0.007) were associated with a lower risk. Recent cerebral magnetic resonance imaging activity, evidence of spinal cord lesions and oligoclonal bands in the cerebrospinal fluid were not associated with the risk of conversion.

Conclusion: Risk of secondary progressive multiple sclerosis increases with age, duration of illness and worsening disability and decreases with improving disability. Therapy may delay the onset of secondary progression.
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http://dx.doi.org/10.1177/1352458519868990DOI Listing
January 2020

Real-World Effectiveness and Safety of Fingolimod in Patients With Relapsing Remitting Multiple Sclerosis: A Prospective Analysis in Buenos Aires, Argentina.

Clin Neuropharmacol 2019 Sep/Oct;42(5):163-166

Sección Enfermedades Desmielinizantes, Servicio de Neurología, Hospital Italiano de Buenos Aires, Argentina.

Objectives: The aim of this prospective observational postmarketing study was to evaluate fingolimod effectiveness in a real-world setting in Buenos Aires, Argentina.

Methods: Relapsing remitting multiple sclerosis patients who had been prescribed fingolimod owing to treatment failure and had at least greater than or equal to 24 months of follow-up were included during August 2013 and June 2018. Three-monthly clinical evaluations and 12-monthly magnetic resonance were performed. Demographic and clinical variables were described as well as the safety and the effectiveness outcomes that included the proportion of patients free from clinical relapses, from disability progression, from new or enlarging T2 or T1 gadolinium-enhancing lesions on annual magnetic resonance imaging, and from any disease activity during the follow-up.

Results: A total of 97 patients were included (68% female [n = 66]; mean ± SD age, 30 ± 10.5 years; mean ± SD disease duration, 6.5 ± 3.1 years; mean ± SD Expanded Disability Status Scale, 3.5 ± 1; mean ± SD fingolimod use, 30 ± 13 months [range, 18-56 months]). One hundred percent (97) used previous disease-modifying therapy, mainly interferons (87%; n = 84). Fourteen patients (14.4%) discontinued/withdrew fingolimod (10 owing to disease activity and 4 owing to tolerance and personal decisions). Eighty-two percent were free from clinical relapses, and 85% were free from disability progression; 75% of patients remained free from new or newly enlarging T2 lesions, and 78% of patients were free from gadolinium enhancing lesions. The proportion of patients free from any disease activity was 54%.

Conclusions: The effectiveness of fingolimod in a newly real-world setting was consistent with information provided from phase III clinical trials.
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http://dx.doi.org/10.1097/WNF.0000000000000358DOI Listing
March 2020

The Argentinean multiple sclerosis registry (RelevarEM): Methodological aspects and directions.

Mult Scler Relat Disord 2019 Jul 15;32:133-137. Epub 2019 May 15.

Centro de esclerosis múltiple de Buenos Aires, Hospital Italiano de Buenos Aires, Gascón 450,1181, Buenos Aires, Argentina.

Despite that different registries already exist in various countries in Europe and North America, no ongoing nationwide registry exists in Latin America (LATAM), a region where the disease behaves differently than in other regions. The objective of this document is to describe the methodology behind RelevarEM, the first nationwide MS registry in Argentina and LATAM. METHODS: In this article, we described the creation, implementation and data management of the nationwide MS registry in Argentina. The registry contains information on the structure, ethical aspects, implementation and variables of the registry (Clinical Trials registry number NCT NCT03375177). CONCLUSION: RelevarEM is the first MS nationwide registry in Argentina, as well as in LATAM, with the objective of providing reliable real-world data of MS in the country.
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http://dx.doi.org/10.1016/j.msard.2019.05.004DOI Listing
July 2019

Brain and spinal MRI features distinguishing MS from different AQP4 antibody serostatus NMOSD at disease onset in a cohort of Latin American patients.

Mult Scler 2020 07 24;26(8):945-954. Epub 2019 May 24.

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

Objective: We aimed to evaluate magnetic resonance imaging (MRI) previously used criteria (Matthews's criteria, MC) for differentiating multiple sclerosis (MS) from neuromyelitis optica spectrum disorders (NMOSD) in Caucasian and non-Caucasian populations (Argentina, Brazil and Venezuela) with positive (P-NMOSD), negative (N-NMOSD), and unknown (U-NMOSD) aquaporin-4 antibody serostatus at disease onset and to assess the added diagnostic value of spinal cord MRI in these populations.

Methods: We reviewed medical records, and MRIs were assessed by two blinded evaluators and were scored using MC. Short-segment transverse myelitis (STM) was added as a new criterion. MC sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined.

Results: We included 282 patients (MS = 188 and NMOSD = 94). MC applied to the entire cohort showed 97.8% sensitivity, 82.9% specificity, 92.0% PPV, and 95.1% NPV for differentiating MS from NMOSD. A subanalysis applied only to non-Caucasian (MS = 89 and NMOSD = 47) showed 100% sensitivity, 80.8% specificity, 90.8% PPV, and 100% NPV. Similar sensitivity, specificity, PPV, and NPV of MC for MS versus P-NMOSD ( = 55), N-NMOSD ( = 28), and U-NMOSD ( = 21) were observed.

Conclusion: MC distinguished MS from NMOSD of all serostatus in a Latin American cohort that included non-Caucasian populations. Addition of STM to MC did not raise the accuracy significantly.
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http://dx.doi.org/10.1177/1352458519849517DOI Listing
July 2020

[Clinical and radiological outcomes measures in progressive multiple sclerosis].

Medicina (B Aires) 2019 ;79(1):37-43

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

During recent years, the development of measures to assess the accumulation of disability and inflammatory activity in the progressive forms of multiple sclerosis (MS) has been a central point of research in various groups. Several instruments have been developed and implemented in order to accurately and early identify the activity and progression in this MS phenotype. Many of these tools, with greater or lesser sensitivity, have been used in clinical trials, although their use in healthcare practice is not entirely familiar to professionals involved in the care of patients with MS. The objective of this review is to describe the clinical and imaging evaluation measures implemented during the last years to identify the activity and the evolution of the disease in its progressive forms.
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March 2020

Validation of CSF free light chain in diagnosis and prognosis of multiple sclerosis and clinically isolated syndrome: prospective cohort study in Buenos Aires.

J Neurol 2019 Jan 1;266(1):112-118. Epub 2018 Nov 1.

Multiple Sclerosis Center of Buenos Aires, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.

Background: The objective was to evaluate the precision of kappa and lambda free light chains (KFLC and LFLC) in CSF for the diagnosis of multiple sclerosis (MS) and prognosis of clinically isolated syndrome (CIS).

Methods: CSF and serum samples from CIS, MS and other neurological non-MS disease were collected between 2015 and 2017. FLC concentrations were measured using immunoassay Freelite™. Results were correlated with the patients' diagnoses and ROC curve analysis was used to determine accuracy. In CIS patients, analysis of FLC were compared in CIS converters vs. non-converter during follow-up.

Results: In the MS group (n = 41), the optimal cut-off for KFLC determined was 7 mg/L, with a diagnostic sensitivity and specificity of 95% and 97%, respectively. The optimal cut-off for LFLC was 0.7 mg/L, with a diagnostic sensitivity and specificity of 71% and 81%, respectively. 36 CIS patients were included; mean follow-up time was 28 ± 9 months, and 22 (61.1%) patients converted to MS. The median concentration of CSF K and LFLCs at CIS diagnosis was slightly higher in CIS-converters compared to non-converters, but this did not reach statistical significance (KFLC: median 7 ± 5.3 mg/L vs. 5 ± 2.3 mg/L, p = 0.11; LFLC 0.7 ± 0.33 mg/L vs. 0.5 ± 0.23 mg/L p = 0.16). A strong correlation was observed between the concentration of K and L FLCs at diagnosis and the change in PBVC during follow-up (r = 0.72 and r = 0.65, respectively).

Conclusion: KFLCs have a high sensitivity and specificity for the diagnosis of MS. FLC concentrations at CIS diagnosis were not significantly higher in CIS-converters.
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http://dx.doi.org/10.1007/s00415-018-9106-2DOI Listing
January 2019