Radiologically isolated syndrome: from biological bases to practical management.

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.

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

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.

Consensus recommendations on the management of multiple sclerosis patients in 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.

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

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.

Argentinean recommendations on the identification of treatment failure in relapsing remitting multiple sclerosis patients.

One of the biggest challenges in multiple sclerosis (MS) is the definition of treatment response/failure in order to optimize treatment decisions in affected patients. The objective of this consensus was to review how disease activity should be assessed and to propose recommendations on the identification of treatment failure in RRMS patients in Argentina. METHODS: A panel of experts in neurology from Argentina, dedicated to the diagnosis and care of MS patients, gathered both virtually and in person during 2016 and 2017 to carry out a consensus recommendation on the identification of treatment failure in RRMS patients. To achieve consensus, the methodology of "formal consensus-RAND/UCLA method" was used. RESULTS: Recommendations were established based on published evidence and the expert opinion. Recommendations focused on disease management, disease activity markers and treatment failure identification were determined. Main consensus were: ≥2 relapses during the first year of treatment and/or ≥3 new or enlarged T2 or T1 GAD+ lesions and/or sustained increase of ≥2 points in EDSS or ≥100% in T25FW defines treatment failure in RRMS patients. CONCLUSIONS: The recommendations of this consensus guidelines attempts to optimize the health care and management of patients with MS in Argentina.

Prevalence and Geographical Variation of Prothrombin G20210A Mutation in Patients with Cerebral Vein Thrombosis: A Systematic Review and Meta-Analysis.

OBJECTIVES: To compare the prevalence of prothrombin G20210A in patients with objectively confirmed cerebral vein or cortical vein thrombosis against healthy controls, and evaluate geographical variations. DESIGN: Systematic review and meta-analysis of case control studies. METHODS: We conducted a systematic review of electronic databases including MEDLINE and EMBASE. The main outcome was the prevalence of prothrombin G20210A in patients with objectively confirmed cerebral vein or cortical vein thrombosis; we also analyzed individual country variations in the prevalence. The random-effects model OR was used as the primary outcome measure. RESULTS: In total 19 studies evaluated 868 cases of cerebral venous thrombosis and 3981 controls. Prothrombin G20210A was found in 103/868 of the patients with cerebral venous thrombosis and 105/3999 of the healthy controls [random effects pooled OR 5.838, 95% CI 3.96 to 8.58; I217.9%]. The prevalence of prothrombin G20210A was significantly elevated in Italian studies (OR 9.69), in Brazilian studies (OR 7.02), and in German studies (OR 3.77), but not in Iranian studies (OR 0.98). CONCLUSION: Prothrombin G20210A is significantly associated with cerebral venous thrombosis when compared to healthy controls, although this association is highly dependent on the country of origin.