[Core data set for real world data in multiple sclerosis: customization for latin america from a global task force recommendation]. / Core data set para la generación de datos de la vida real en esclerosis múltiple: adaptación de una iniciativa global para América Latina.

INTRODUCTION: The primary objective of the core data set is to reduce heterogeneity and promote harmonization among data sources in EM, thereby reducing the time needed to execute real life data collection efforts. Recently, a group led by the Multiple Sclerosis Data Alliance has developed a core data set for collecting real-world data on multiple sclerosis (MS) globally. Our objective was to adapt this global data set to the needs of Latin America, so that it can be implemented by the registries already developed and in the process of development in the region. MATERIAL AND METHODS: A working group was formed regionally, the core data set created globally was adapted (translation process into Spanish, incorporation of regional variables and consensus on variables to be used). Consensus was obtained through the remote Delphi methodology of a round of questionnaires and remote discussion of the core data set variables. RESULTS: A total of 25 professionals from Latin America carried out the adaptation process between November 2022 and July 2023. Agreement was established on a core data set of nine categories and 45 variables, version 2023 to suggest its implementation in developed or developing registries, and MS cohorts in the region. CONCLUSION: The core data set seeks to harmonize the variables collected by registries and cohorts in MS in Latin America in order to facilitate said collection and allow collaboration between sources. Its implementation will facilitate real life data collection and collaboration in the region.

TITLE: Core data set para la generación de datos de la vida real en esclerosis múltiple: adaptación de una iniciativa global para América Latina.Introducción. Los objetivos primarios del core data set son reducir la heterogeneidad y promover la armonización entre las fuentes de datos en la esclerosis múltiple (EM), reduciendo así el tiempo necesario para ejecutar esfuerzos en la recolección de datos de vida real. Recientemente, un grupo liderado por la Multiple Sclerosis Data Alliance ha desarrollado un core data set para la recolección de datos del mundo real en EM a nivel global. Nuestro objetivo ha sido adaptar y consensuar este conjunto de datos globales a las necesidades de América Latina para que pueda ser implementado por los registros ya desarrollados y en proceso de desarrollo en la región. Material y métodos. Se conformó un grupo de trabajo regionalmente y se adaptó el core data set creado globalmente (proceso de traducción al español, incorporación de variables regionales y consenso sobre variables que se iban a utilizar). El consenso se obtuvo a través de la metodología Delphi remoto de ronda de cuestionarios y discusión a distancia de las variables del core data set. Resultados. Veinticinco profesionales de América Latina llevaron adelante el proceso de adaptación entre noviembre de 2022 y julio de 2023. Se estableció un acuerdo sobre un core data set de nueve categorías y 45 variables, versión 2023, con la sugerencia de implementarlo en registros desarrollados o en vías de desarrollo y cohortes de EM en la región. Conclusión. El core data set busca armonizar las variables recolectadas por los registros y las cohortes de EM en América Latina con el fin de facilitar dicha recolección y permitir una colaboración entre fuentes. Su implementación facilitará la recolección de datos de vida real y la colaboración en la región.

Uveitis intermedia as the initial presentation of a primary lymphoma of the central nervous system.

Primary central nervous system lymphoma is one of the most infrequent brain tumours, accounting for 3% of primary central nervous system neoplasms. In addition to its low prevalence, clinical presentation is usually nonspecific, leading to diagnostic delay. Intraocular involvement occurs in 15% of cases, and disease onset in this location is even rarer. We present a case of a patient with intermediate uveitis as the first clinical manifestation of this neoplasm.

Uveitis intermedia as the initial presentation of a primary lymphoma of the central nervous system. / Uveítis intermedia como presentación inicial de un linfoma primario del sistema nervioso central.

Primary central nervous system lymphoma is one of the most infrequent brain tumours, accounting for 3% of primary central nervous system neoplasms. In addition to its low prevalence, clinical presentation is usually nonspecific, leading to diagnostic delay. Intraocular involvement occurs in 15% of cases, and disease onset in this location is even rarer. We present a case of a patient with intermediate uveitis as the first clinical manifestation of this neoplasm.

[Argentinean consensus guidelines on the identification and clinical care of secondary progressive multiple sclerosis]. / Consenso sobre la identificación y seguimiento de la esclerosis múltiple secundaria progresiva en Argentina.

INTRODUCTION: The identification, diagnosis, follow-up, and treatment of patients with secondary progressive multiple sclerosis (SPMS) show significant differences between health care professionals in Argentina. AIM: To provide consensus recommendations on the management of patients with SPMS in Argentina to optimize patient care. DEVELOPMENT: A panel of expert neurologists from Argentina dedicated to the diagnosis and care of multiple sclerosis patients gathered during 2019 and 2020 to carry out a consensus recommendation on the diagnosis and treatment of SPMS patients in Argentina. To achieve consensus, the methodology of 'formal consensus-RAND/UCLA method' was used. Recommendations were established based on published evidence and the expert opinion. Recommendations focused on how to define SPMS and how to follow SPMS patients. CONCLUSION: The recommendations of this consensus guidelines attempt to optimize the care of SPMS patients in Argentina.

TITLE: Consenso sobre la identificación y seguimiento de la esclerosis múltiple secundaria progresiva en Argentina.Introducción. Existen diferencias significativas en el diagnóstico, la identificación y el seguimiento de pacientes con esclerosis múltiple secundaria progresiva (EMSP) entre los profesionales de la salud a cargo de su tratamiento. Objetivo. Proveer recomendaciones sobre el tratamiento de los pacientes con EMSP en Argentina con el fin de optimizar su cuidado. Desarrollo. Un grupo de neurólogos expertos en esclerosis múltiple de Argentina elaboró un consenso para el tratamiento de pacientes con EMSP en la región mediante metodología de ronda de encuestas a distancia y reuniones presenciales. Se establecieron 33 recomendaciones basadas en la evidencia publicada y en el criterio de los expertos que participaron. Las recomendaciones se enfocaron en el diagnóstico y el seguimiento de los pacientes con EMSP. Conclusión. Las recomendaciones establecidas en el presente consenso permitirían optimizar el cuidado y el seguimiento de los pacientes con EMSP en Argentina.

Disease activity impacts disability progression in primary progressive multiple sclerosis.

BACKGROUND: Although solid information on the natural history of primary progressive multiple sclerosis (PPMS) is available, evidence regarding impact of disease activity on PPMS progression remains controversial. OBJECTIVE: To describe the clinical characteristics, presence or absence of MRI activity, and natural history of a PPMS cohort from two referral centers in Argentina and assess whether clinical and/or radiological disease activity correlated with disability worsening. METHODS: Retrospective study conducted at two MS clinics in Buenos Aires, Argentina, through comparative analysis of patients with and without evidence of disease activity. RESULTS: Clinical and/or radiologic activity was presented in 56 (31%) of 178 patients. When stratified by age at onset, we found that for every 10 years of increase in age at onset, risk of reaching EDSS scores of 4 and 6 increased by 26% and 31%, respectively (EDSS 4: HR 1.26, CI 95%: 1.06-1.50; EDSS 6: HR 1.31, CI 95%: 1.06-1.62). Patients who presented clinical exacerbations reached EDSS scores of 6, 7 and 8 faster than those without associated exacerbations (p = 0.009, p = 0.016 and p = 0.001, respectively). Likewise, patients who presented gadolinium-enhancing lesions during the course of disease reached EDSS scores of 7 earlier (p = 0.002). CONCLUSION: Older age at onset and presence of clinical and/or radiological disease activity correlated with accelerated disability progression in this cohort of PPMS patients.

Brain volume loss and no evidence of disease activity over 3 years in multiple sclerosis patients under interferon beta 1a subcutaneous treatment.

The objective of our study was to evaluate the relationship of percentage of annualized brain volume loss (aBVL) and no evidence of disease activity (NEDA) in multiple sclerosis (MS) patients under interferon beta 1-a subcutaneous treatment (IFN-beta) during 3 years of follow up. Relapsing remitting MS (RRMS) patients, with less than three years from disease onset, expanded disability status scale (EDSS) ≤3 and in which IFN beta 1-a 44 mcg was indicated, were included. Demographic, clinical and structural parameters from the magnetic resonance (MR) during the 3 years of follow up were analyzed and compared between patients with and without NEDA (defined as the absence of: (a) three-month confirmed disability progression defined as an increase in EDSS score of 1.0; (b) confirmed relapses; and (c) new or enlarged T2 lesions and/or Gd+ lesions). A total of 87 patients, mean age 33 ±â€¯6 years were included. NEDA was reached by 39 patients at year 3. Percentage of aBVL from baseline to months 24 in NEDA patients was -1.1% vs. -1.54% in patients without NEDA (p < 0.001) and from baseline to month 36 it was -1.43% vs. -2.1% (p < 0.001) in patients with and without NEDA, respectively. At 3 years follow up, patients who received IFN beta 1a and were disease-free had lower percentage of aBVL compared to patients with disease activity.

[Primary lymphoma of the anterior pituitary in an immunocompetent patient]. / Linfoma primario de adenohipofisis en una paciente inmunocompetente.

TITLE: Linfoma primario de adenohipofisis en una paciente inmunocompetente.

Brain structural changes in patients in the early stages of multiple sclerosis with depression.

Some studies suggest an inflammatory mechanism associated with the presence of depression in multiple sclerosis (MS); however, there is little data concerning these findings. The purpose of this study was to investigate the presence of brain structural changes in patients with MS and depression and to compare them with patients suffering from MS without depression and healthy controls. METHODS: A case-control study that included patients with relapsing-remitting MS (RRMS) defined by validated criteria, over 18 years of age, with less than three years from disease onset, EDSS ≤ 3, with no history of previous depression and under immunomodulatory treatment with interferon beta, if any. A control group paired by age and gender was also included. Patients were clinically assessed to determine the presence of depression. Demographic clinical and structural aspects of parameters from the scan, such as lesion volume, total brain volume (TBV), white matter volume (WMV), neocortical gray matter volume (NGMV), and fractional anisotropy (FA) were analyzed. RESULTS: Sixty-five individuals were enrolled: 20 healthy controls, 22 patients with MS without depression, and 23 patients with MS with depression. Patients with MS and depression showed a lower TBV (P = 0.01), NGMV (0.01) together with an increase in lesion burden in T2 (P < 0.01) but not in T1 (P = 0.09) and no differences in global FA among groups (P = 0.23) and in WMV (P = 0.12). CONCLUSION: Patients with RRMS and depression had a reduced total brain volume and a significantly increased lesion burden at T2 MR than patients with RRMS without depression.

Gender ratio trends over time in multiple sclerosis patients from Argentina.

Several studies in multiple sclerosis (MS) suggest a trend of increasing disease frequency in women during the last decades. A direct comparison of gender ratio trends among MS populations from Argentina remains to be carried out. The objective of the study was to compare gender ratio trends, over a 50-year span in MS populations from Argentina. METHODS: multicenter study that included patients from 14 MS Centers of Argentina. Patients with definite MS with birth years ranging from 1940 to 1989 were included. Gender ratios were calculated by five decades based on year of birth and were adjusted for the F/M born-alive ratio derived from the Argentinean national registry of births. The F/M ratios were calculated using a multivariate logistic regression per five decades by the year of birth approach. Analyses were performed using Stata 10.1. RESULTS: 1069 patients were included. Gender ratios showed a significant increase from the first to the last decade in the whole MS sample (from 1.8 to 2.7; p value for trend=0.023). The Gender ratio did not show differences considering MS subtype. CONCLUSION: our study showed a modest increase of the F/M ratio (from 1.8 to 2.7) over time among patients affected by MS in Argentina.

Increasing prevalence of multiple sclerosis in Buenos Aires, Argentina.

UNLABELLED: In 1996, the prevalence of multiple sclerosis (MS) for the metropolitan area of Buenos Aires using the capture-recapture method was estimated to be between 14 and 19.8 cases per 100,000 inhabitants. The aim of this study was to update the prevalence to 2014 following the same methodology. METHODS: Gran Buenos Aires is the denomination that refers to the megalopolis comprised by the autonomous city of Buenos Aires and the surrounding conurbation of the province of Buenos Aires. The study was carried out taking December 2014 as the prevalence month. We used the capture-recapture method to estimate the prevalence of MS cross-matching registries from 6 MS Centers from the metropolitan area of Buenos Aires. Log-linear model Poisson regression was used to estimate the number of affected MS patients not detected by any of the 6 sources considered. RESULTS: 1035 registries were obtained from the 6 lists from 910 different patients detected. The population of the area based on 2010 census was 12,806,866, the number of MS cases estimated amongst source interactions were 4901. The estimated prevalence was 38.2 per 100,000 inhabitants (95% CI 36.1-41.2). CONCLUSION: The study is an update almost 20 years after the first one in the area showing a significant increase in the previous reported prevalence. Our findings are in line with previous studies performed in other regions of the world.

Increasing incidence of multiple sclerosis among women in Buenos Aires: a 22 year health maintenance organization based study.

Studies in multiple sclerosis (MS) suggest a trend of increasing disease prevalence and incidence, and especially, a disproportional increase in the incidence of multiple sclerosis in women. The objective of this study was to evaluate the incidence of MS over 22 years and to determine the ratio in incidence of men to women in a health maintenance organization from Buenos Aires, Argentina. The population was made up of all members of a hospital-based HMO affiliated between January 1992 and December 2013. Each person was followed contributing time at risk. Cases with definite diagnosis of MS were included. Incidence density was calculated with 95 % confidence intervals and compared between women and men. 165,456 subjects were followed for a total of 1,488,575 person-years, of whom 42 developed MS. Incidence density was 3/100,000 person-years (95 % CI 2.1-3.5/100,000 person-years). During this period (1992-2013), the incidence rate in women increased from 1/100,000 (95 % CI 0.8-1.6) to 4.9/100,000 (95 % CI 4.1-5.4) (p < 0.001), while in men the incidence ranged from 1.4/100,000 (95 % CI 1-1.7) to 1.8 (1.3-2.1) (p = 0.16). Incidence density during the study period increased significantly in women but not in men. This is the first report of this phenomenon in Latin America region.

Disease onset in familial and sporadic multiple sclerosis in Argentina.

UNLABELLED: The present study was carried out to assess if there is an anticipation of age at onset in younger generations of familial multiple sclerosis (FMS) vs. sporadic MS (SMS) in Argentina. METHODS: multicenter study that included patients from 14 MS Centers of Argentina. Patients were considered as FMS if they had in their family at least one relative of first or second degree diagnosed with MS; otherwise, patients were considered to have SMS. We compared the age at onset between familial and sporadic cases as well as the age at onset between relatives from different generations in FMS vs. SMS. RESULTS: 1333 patients were included, 97 of them were FMS (7.3%). A lower age at onset in the younger generations of FMS cases was found compared with older generations of FMS as well as. SMS cases (24.1±3.7 years vs. 30.3±5.7 years, and 32.4±9.4 respectively; p<0.001). No differences were observed between older generations of FMS vs. SMS cases (p=0.12). CONCLUSION: we observed an anticipation of age at onset of MS in younger generations of patients with FMS vs. older generations of FMS and SMS.

Application of the McDonald 2010 criteria for the diagnosis of multiple sclerosis in an Argentinean cohort of patients with clinically isolated syndromes.

BACKGROUND: The International Panel on Diagnosis of Multiple Sclerosis has proposed new magnetic resonance imaging (MRI) criteria for the diagnosis of multiple sclerosis (MS) in patients with clinically isolated syndrome (CIS). We aimed to evaluate these new criteria in a cohort of patients from Buenos Aires, Argentina. METHODS: Patients with CIS, in whom MRI was performed within three months of onset of symptoms, were included between January 2005-June 2010. Poser or McDonald 2005 criteria were used as gold standard diagnostic criteria for MS. MRI was assessed by a blind evaluator identifying recently diagnostic MS criteria. New criteria sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were determined. RESULTS: Altogether 101 patients were included. Of these, 86 patients converted to MS (McDonald 2005/Poser) during the follow-up. The mean follow-up time was 7.3±3.2 years (range 1.8-11 years). Sensitivity was 84%, specificity 80%, PPV 96%, NPV 46% and accuracy 82%. The sub-analysis applied only to non-European descendants (mestizos, natives and zambos) showed a high level of accuracy for these new diagnostic criteria in this local ethnic/genetic population (sensitivity 77%, specificity 72%, PPV 94%, NPV 38%). CONCLUSIONS: This study assessing McDonald 2010 criteria in a Latin-American population may contribute to its international validation.

[Sex-related differences in atrophy and lesion load in multiple sclerosis patients]. / Diferencias en la tasa de atrofia global y regional y del volumen lesional entre género en esclerosis múltiple.

INTRODUCTION: Previous studies showed gender-associated clinical and MRI differences in multiple sclerosis (MS) evolution. However, only few studies were done with non conventional MRI techniques and no one was done in a South American MS population. The aim of this study was to investigate gender differences according to nonconventional MRI measures in patients with MS from Buenos Aires, Argentina. METHODS: Relapsing-remitting MS patients (RRMS) with at least 6 years of follow up and an MRI at onset and at 6 years were included. Patients were assessed using nonconventional MRI measures: total brain volume (TBV), neocortical grey brain volume (GBV), white brain volume (WBV), lesion load (LL), % of brain volume change between onset and year 6 (% BVC) and regional brain volume change. Gender-related MRI differences were investigated using general linear model analysis. RESULTS: The 45 patients were included (25 female). Mean follow up time was 7.3 ± 0.2 years. No differences in age, EDSS at onset, DMD treatment, TBV, GBV, WBV neither LL were found between gender at baseline. Six years later, males showed a decrease in TBV (P=.002) and GBV (P ≤ 0.001) and an increase in LL (P=.02) and % BVC (P<.001) vs. females. Female patients showed a decrease in the volume of frontal subcortical region. DISCUSSION: This is the first study showing differences in brain volume changes between gender in MS patients from South America. Future studies will confirm our initial findings.

Oligoclonal bands in multiple sclerosis patients: worse prognosis?

INTRODUCTION: Cerebrospinal fluid (CSF) oligoclonal bands (OB) imply intrathecal immunoglobulin synthesis and B-cell immune process. There is scarce evidence of OB having a role in disease prognosis. The objective of the present study was to determine OB's prognostic value regarding disease progression. METHODS: Between January 1994 and January 2007, relapsing-remitting MS (RRMS) patients in which OB were determined were included. Demographic, clinical aspects and presence of OB were analyzed. We compared OB+ versus OB- patients regarding progression to expanded disability status scale (EDSS) of 6·0 and to secondary progressive MS (SPMS). Cox proportional hazard models were used to compare the outcome between groups. P values <0·05 were considered significant. RESULTS: One hundred and ninety-six patients were included. In 176 patients (90%), the CSF showed type II OB, 20 (10%) patients were OB negative. There were no differences between age, clinical presentation and EDSS at onset or in the immunomodulatory treatment received between OB+ and OB- patients. Sixty-two (31·6%) patients converted to SPMS during the follow-up, 59 (33·5%) were OB+ and 3 (15%) were OB-. EDSS of 6 was recorded in 56 (28·5%) patients during the follow-up; 54 (31%) were OB+ while only 2 (10%) OB- patients reached this outcome (reach SP phase, P = 0·032; HR: 2·2; 95% CI: 1·3-7·5 and EDSS of 6, P = 0·037; HR: 1·9; 95% CI: 1·3-8·5). CONCLUSION: We observed during the follow-up that OB- patients had a better prognosis and milder disability compared to OB+ patients.

Assessing the value of spinal cord lesions in predicting development of multiple sclerosis in patients with clinically isolated syndromes.

The purpose of this study was to determine the value of spinal cord lesions as a predictive factor for conversion in clinically isolated syndrome (CIS) patients. Patients with CIS and without immunomodulatory treatment were prospectively included. Age at onset, sex, clinical syndrome at onset, oligoclonal bands, and presence, number and location of lesions on brain and spinal MRI were analyzed. Conversion to multiple sclerosis (MS) was the primary endpoint. Cox regression was used to compare outcomes between groups. A total of 75 patients were included: 53 (71%) women, mean age at onset 32.7 years (SD ± 7.5), mean follow-up time 72.5 months (SD ± 9; range 17-104 months). There were 11 (14.6%) patients with one focal spinal cord lesion, while 13 (17%) patients had two or more spinal cord lesions at the first scan during the onset of the disease. Of the 23 patients (30.6%) who converted to clinically definite MS (CDMS), 2 had a normal spinal cord MRI, 8 patients had one spinal cord lesion, and 13 had more than one lesion on MRI (p < 0.001). In multivariable analyses, one focal spinal cord lesion was significantly associated with increased risk of conversion to MS (p = 0.01, HR 3.5, CI 95% 2.1-6.9), while the presence of two or more focal spinal cord lesions was independently associated with a higher risk of conversion to MS (p < 0.001, HR 5.9, CI 95% 3.2-10.8). CIS patients with an abnormal baseline spinal cord MRI have a higher risk for developing clinically definite MS, independent of brain lesions as well as the presence of cerebrospinal fluid oligoclonal banding (OSF-OB) .

[Acute transverse myelitis in Buenos Aires, Argentina. A retrospective cohort study of 8 years follow up]. / Mielitis transversa aguda en Buenos Aires, Argentina. Estudio de una cohorte retrospectiva de 8 años de seguimiento.

INTRODUCTION: Epidemiological studies on acute transverse myelitis (ATM) in South America are scarce. The aim of our study was to describe demographic, clinical and para-clinical features of patients with ATM in a health care organisation in Buenos Aires. A further objective was to determine the aetiologies of ATM. METHODS: All patients diagnosed with ATM between June 1, 2002 and June 30, 2010 were retrospectively identified, using the Transverse Myelitis Consortium Working Group criteria. RESULTS: A total of 40 patients diagnosed with ATM, (24 females, 60%) were included. The mean follow-up was 57 ± 8 months. The principal cause of myelitis found was ATM secondary to demyelinating disease (55%). Idiopathic ATM was diagnosed in 15 (37.5%) cases in the sample. The majority of patients had an extensive cord lesion (50%) detectable with spinal MRI. CONCLUSION: There are few epidemiological studies concerning ATM in Argentina, and we believe that it is important to be aware of the manner in which this condition manifests itself in this region. We would therefore be able to compare them with studies previously published in other countries.

CD24 as a genetic modifier of disease progression in multiple sclerosis in Argentinean patients.

INTRODUCTION: Previous reports have shown that CD24 gene polymorphisms have an important role in the risk of development and progression of multiple sclerosis (MS). OBJECTIVE: To investigate the association between P226 polymorphisms (T/C), P1056 (A/G), P1527 (TG/del) and P1626 (A/G) of the CD24 gene and MS, comparing allele and genotype frequencies of patients versus controls. MATERIALS AND METHODS: We analyzed DNA samples from 102 MS patients and from 205 unrelated healthy individuals. DNA was extracted from peripheral blood and polymorphic regions were amplified by nested PCR. Genotyping was performed by restriction fragments length polymorphisms. Time from disease onset to reach EDSS 6 and time to conversion to secondary progressive phase (SP) were used as variables of survival as well as percentage of patients that reached those endpoints. We used the log Rank test for data comparison (significant p≤0.05). RESULTS: We found no differences between cases and controls in frequency of polymorphisms at the CD24 gene. 44.6% of patients with the AA genotype (P1626) reached an EDSS 6 vs 16% of patients with other genotypes (p<0.001, HR 3.2, 95% CI 1.4 to 7.4). 45.8% of patients with the AA genotype reached SPMS vs 16.7% without this genotype (p<0.001, HR 3.4, 95% CI 1.5 to 7.8). CONCLUSIONS: This study showed a strong association between the presence of AA genotype in the 1626 polymorphism of the CD24 gene and the risk of disease progression in MS patients.