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OBJECTIVE: Susac syndrome (SuS), multiple sclerosis (MS), and primary angiitis of the central nervous system (PACNS) present diagnostic challenges due to overlapping clinical features. We aimed to enhance diagnostic precision by developing the SPAMS (SuS, PACNS, MS) score, a practical radiological tool. METHODS: This multicenter study included 99 patients (43 SuS, 37 MS, 19 PACNS) from South American countries. Relevant MRI features were identified through an elastic-net model determined key variables. RESULTS: The SPAMS score assigned 2 points for snowball lesions, 1 point for spokes-like lesions, or if there are more than 4 lesions in the corpus callosum, corpus callosum involvement, or cerebellar involvement. It subtracted 1 point if gadolinium-enhancing lesions or 4 points if Dawson's fingers are present. Bootstrapping validated the optimal cutoff at 2 points, exhibiting a diagnostic performance of area under the curve = 0.931, sensitivity = 88%, specificity = 89%, positive predictive value = 88%, negative predictive value = 89%, and accuracy = 88%. INTERPRETATION: When specific MRI findings coexisted, the SPAMS score differentiated SuS from MS and PACNS. Access to MRI and standard protocol sequences makes it a valuable tool for timely diagnosis and treatment, potentially preventing disability progression and severe clinical outcomes. ANN NEUROL 2024.
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BACKGROUND AND OBJECTIVES: Primary-progressive multiple sclerosis (PPMS) is characterized by gradual neurological deterioration without relapses. This study aimed to investigate the clinical impact of gender and age at disease onset on disease progression and disability accumulation in patients with this disease phenotype. METHODS: Secondary data from the RelevarEM registry, a longitudinal database in Argentina, were analyzed. The cohort comprised patients with PPMS who met inclusion criteria. Statistical analysis with multilevel Bayesian robust regression modeling was conducted to assess the associations between gender, age at onset, and Expanded Disability Status Scale (EDSS) score trajectories. RESULTS: We identified 125 patients with a confirmed diagnosis of PPMS encompassing a total of 464 observations. We found no significant differences in EDSS scores after 10 years of disease progression between genders (-0.08; credible interval (CI): -0.60, 0.42). A 20-year difference in age at onset did not show significant differences in EDSS score after 10 years of disease progression (0.281; CI: -0.251, 0.814). Finally, we also did not find any clinically relevant difference between gender EDSS score with a difference of 20 years in age at onset (-0.021; CI: -0.371, 0.319). CONCLUSION: Biological plausibility of gender and age effects does not correlate with clinical impact measured by EDSS score.
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Esclerosis Múltiple Crónica Progresiva , Esclerosis Múltiple , Humanos , Masculino , Femenino , Niño , Esclerosis Múltiple Crónica Progresiva/diagnóstico , Edad de Inicio , Teorema de Bayes , Recurrencia Local de Neoplasia , Progresión de la EnfermedadRESUMEN
BACKGROUND: We assessed the effectiveness, safety and patient-reported outcomes (PROs) of dimethyl fumarate (DMF) in real-world clinical practice in patients with multiple sclerosis (PwMS) from Argentina. METHODS: We conducted a multicenter ambispective cohort study in Argentina between September 2020 and March 2023. Changes in annualized relapse rate (ARR), Expanded Disability Status Scale (EDSS) score, magnetic resonance imaging (MRI), no evidence of disease activity (NEDA), PROs (depression, anxiety, fatigue, burden of treatment and quality of life), and safety data were collected at clinical visits performed every 6 months for at least 24 months. RESULTS: We included 161 PwMS (64% female). DMF treatment was associated with a significant reduction in ARR from baseline after 24 months of treatment (from 0.87 to 0.23, p < 0.001). Disability progression was observed in 27.9% vs. 9.3% pre- and post-DMF, and disability improvement was found in 13% of patients from baseline to month 24. MRI activity was significantly reduced compared with baseline. Fatigue, depression, and quality of life scores were significantly improved from baseline to 24 months. Flushing was the most frequent adverse event reported in 19.2%. No significant reduction was observed in the hospitalization rate pre- and post-DMF (19.8% vs. 5.6%, p = 0.32). During follow-up, 135 (83%) patients were relapse-free, 110 (68.3%) were MRI free activity (Gad + lesion) and 108 (67%) reached NEDA. CONCLUSIONS: DMF significantly reduced disease activity in PwMS from Argentina with a good safety profile in real-world settings. A significant impact on the quality of life during follow-up was found.
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We aimed to evaluate the incidence of SARS-CoV-2 breakthrough infection of SARS-CoV-2 vaccines in people with MS (PwMS) on high-efficacy disease-modifying therapies (HET) included in the national MS registry in Argentina (RelevarEM). METHODS: Non-interventional, retrospective cohort study that collected information directly from RelevarEM. Adult PwMS who had been treated for at least 6 months with a HET (ocrelizumab, natalizumab, alemtuzumab, cladribine) who had received at least two doses of SARS-CoV-2 vaccines available in Argentina were included. Full course of vaccination was considered after the second dose of the corresponding vaccines. Cumulative incidence of SARS-CoV-2 infection was reported for the whole cohort by Kaplan-Meier survival curves (which is expressed in percentage) as well as incidence density (which is expressed per 10.000 patients/day with 95% CI). RESULTS: Two hundred twenty-eight PwMS were included. Most frequent first and second dose received was AstraZeneca vaccine, followed by Sputnik vaccine. Most frequent HETs used in included patients were cladribine in 79 (34.8%). We found an incidence density of breakthrough COVID-19 infection of 3.5 × 10.000 patients/day (95% CI 2.3-6.7) after vaccination in Argentina. We described the incidence rate after vaccination for every HET used, it being significantly higher for ocrelizumab compared with other HETs (p = 0.005). Only five patients presented a relapse during the follow-up period with no differences regarding the pre-vaccination period. CONCLUSIONS: We found an incidence density of breakthrough COVID-19 infection of 3.5 × 10.000 patients/day (95% CI 2.3-6.7) after vaccination in Argentina.
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Infección Irruptiva , COVID-19 , Esclerosis Múltiple , Adulto , Humanos , Argentina/epidemiología , Cladribina , Vacunas contra la COVID-19/uso terapéutico , Incidencia , Estudios RetrospectivosRESUMEN
Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease of the central nervous system characterized by severe attacks of optic neuritis, myelitis, and/or area postrema. Advances in understanding the pathophysiology of NMOSD have led to improved diagnostic and therapeutic approaches. There has been a notable increase in research efforts worldwide, including in Latin America (LATAM). In recent years, LATAM has witnessed a surge in research on NMOSD, resulting in a growing body of evidence on various aspects such as epidemiology, clinical manifestations, paraclinical features (including AQP4-IgG [Aquaporin-4-immunoglobulin G] and imaging), acute and long-term treatment strategies, as well as accessibility to diagnostic tests. This narrative review aims to present the most relevant findings from different NMOSD cohorts in LATAM, providing a comprehensive overview of the current understanding of the disease in the region, while considering its unique characteristics and challenges. LATAM-focused evidence is crucial for adding valuable information to the international dataset and is therefore summarized in this review.
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Neuromielitis Óptica , Humanos , América Latina/epidemiología , Neuromielitis Óptica/diagnóstico , Neuromielitis Óptica/epidemiología , Neuromielitis Óptica/terapia , Estudios de Cohortes , Investigación BiomédicaRESUMEN
Neuromyelitis optica spectrum disorder (NMOSD) is a devastating antibody-mediated condition of the central nervous system. As in other autoimmune diseases, there is considerable evidence to suggest that NMOSD arises from complex interactions between genetic susceptibility and environmental factors. However, whether factors like aquaporin-4-Antibody production initiate NMOSD attacks, currently remains unclear, and requires further investigation. Infectious diseases have also been proposed as possible environmental factors associated with NMOSD onset or relapses, some of which are more common in Asia and Latin America than in Europe and North America, in parallel with the higher incidence of NMOSD in these geographic locations. In this review, we examine current evidence on specific infections and vaccines associated with NMOSD onset and/or attacks, as well as the most recent data on gut microbiome composition and SARS-CoV-2 infection in NMOSD patients.
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COVID-19 , Microbioma Gastrointestinal , Neuromielitis Óptica , Humanos , COVID-19/prevención & control , COVID-19/complicaciones , SARS-CoV-2 , Autoanticuerpos , Vacunación , Acuaporina 4RESUMEN
BACKGROUND: Recently, satralizumab (interleukin-6 receptor blocker) was approved for seropositive neuromyelitis optica spectrum disorder (NMOSD) patients. In SAkuraSky trial, mild neutropenia was reported in 15% of patients under satralizumab. Most neutropenias were transient; grade 3-4 was not related to serious infections. So far, no severe neutropenia (<100 cell/mm3) has been reported worldwide. METHODS: We present an aquaporin-4-antibody-positive NMOSD patient who developed severe febrile neutropenia 2 weeks after adding satralizumab to her azathioprine treatment. CONCLUSION: Analytic control for satralizumab is recommended at 4 weeks. However, we recommend this control at week 2, in order to closely monitor neutrophil count and prevent further complications.
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Neutropenia Febril , Neuromielitis Óptica , Humanos , Femenino , Neuromielitis Óptica/complicaciones , Neuromielitis Óptica/tratamiento farmacológico , Acuaporina 4 , Anticuerpos Monoclonales Humanizados , Autoanticuerpos , Neutropenia Febril/inducido químicamenteRESUMEN
BACKGROUND: Information on performance of multiple sclerosis (MS) diagnostic criteria is scarce for populations from Latin America, Asia, or the Caribbean. OBJECTIVE: To assess performance of revised 2017 McDonald criteria as well as evaluate genetic ancestry in a group of MS patients from Argentina experiencing a debut demyelinating event. METHODS: Demographic and clinical characteristics, cerebrospinal fluid (CSF), and magnetic resonance imaging (MRI) findings and new T2 lesions were recorded at baseline and during relapses. Diagnostic accuracy in predicting conversion to clinically defined MS (CDMS) based on initial imaging applying revised 2017 criteria was evaluated and genetic ancestry-informative markers analyzed. RESULTS: Of 201 patients experiencing their first demyelinating event (median follow-up 60 months), CDMS was confirmed in 67. We found 2017 diagnostic criteria were more sensitive (84% vs 67%) and less specific (14% vs 33%) than 2010 criteria, especially in a group of patients revised separately, presenting positive oligoclonal bands (88% vs 8%). Genetic testing performed in 128 cases showed 72% of patients were of European ancestry and 27% presented genetic admixture. CONCLUSION: 2017 McDonald criteria showed higher sensitivity and lower specificity compared with 2010 criteria, shortening both time-to-diagnosis and time-to-treatment implementation.
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Esclerosis Múltiple , Humanos , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/genética , Esclerosis Múltiple/líquido cefalorraquídeo , Argentina , Imagen por Resonancia Magnética , Asia , Bandas Oligoclonales/líquido cefalorraquídeoRESUMEN
BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) misdiagnosis (i.e. the incorrect diagnosis of patients who truly have NMOSD) remains an issue in clinical practice. We determined the frequency and factors associated with NMOSD misdiagnosis in patients evaluated in a cohort from Latin America. METHODS: We retrospectively reviewed the medical records of patients with NMOSD, according to the 2015 diagnostic criteria, from referral clinics in six Latin American countries (Argentina, Chile, Paraguay, Colombia, Ecuador, and Venezuela). Diagnoses prior to NMOSD and ultimate diagnoses, demographic, clinical and paraclinical data, and treatment schemes were evaluated. RESULTS: A total of 469 patients presented with an established diagnosis of NMOSD (73.2% seropositive) and after evaluation, we determined that 56 (12%) patients had been initially misdiagnosed with a disease other than NMOSD. The most frequent alternative diagnoses were multiple sclerosis (MS; 66.1%), clinically isolated syndrome (17.9%), and cerebrovascular disease (3.6%). NMOSD misdiagnosis was determined by MS/NMOSD specialists in 33.9% of cases. An atypical MS syndrome was found in 86% of misdiagnosed patients, 50% had NMOSD red flags in brain and/or spinal magnetic resonance imaging (MRI), and 71.5% were prescribed disease-modifying drugs. CONCLUSIONS: NMOSD misdiagnosis is relatively frequent in Latin America (12%). Misapplication and misinterpretation of clinical and neuroradiological findings are relevant factors associated with misdiagnosis.
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Errores Diagnósticos , Esclerosis Múltiple , Neuromielitis Óptica , Humanos , Acuaporina 4 , Encéfalo/patología , América Latina/epidemiología , Imagen por Resonancia Magnética/métodos , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/epidemiología , Neuromielitis Óptica/diagnóstico por imagen , Neuromielitis Óptica/epidemiología , Estudios RetrospectivosRESUMEN
BACKGROUND: We aimed to assess the frequency of new asymptomatic lesions on brain and spinal imaging (magnetic resonance imaging (MRI)) and their association with subsequent relapses in a large cohort of neuromyelitis optica spectrum disorder (NMOSD) patients in Argentina. METHODS: We retrospectively reviewed 675 MRI (225 performed during an attack and 450 during the relapse-free period (performed at least 3 months from the last attack)) of NMOSD patients who had at least 2 years of clinical and MRI follow-up since disease onset. Kaplan-Meier (KM) curves were used for depicting time from remission MRI to subsequent relapse. RESULTS: We included 135 NMOSD patients (64.4% were aquaporin-4-immunoglobulin G (AQP4-IgG)-positive). We found that 26 (19.26%) and 66 (48.88%) of patients experienced at least one new asymptomatic MRI lesion during both the relapse-free period and attacks, respectively. The most frequent asymptomatic MRI lesions were optic nerves followed by short-segment myelitis during the relapse-free period and attacks. KM curves did not show differences in the time taken to develop a new relapse. CONCLUSION: Our findings showed that new asymptomatic lesions are relatively frequent. However, the presence of new asymptomatic MRI lesions during the relapse-free period and at relapses was not associated with a shorter time to developing subsequent relapses.
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Neuromielitis Óptica , Humanos , Neuromielitis Óptica/diagnóstico por imagen , Neuromielitis Óptica/complicaciones , Estudios Retrospectivos , Estudios de Seguimiento , Encéfalo/diagnóstico por imagen , Acuaporina 4 , Imagen por Resonancia Magnética , AutoanticuerposRESUMEN
OBJECTIVES: We aimed to determinate the frequency of this association and compare the features of neuromyelitis optica spectrum disorder (NMOSD) with and without associated autoimmune diseases (AD) in a Latin American (LATAM) population in clinical practice. METHODS: We retrospectively reviewed the medical records of patients with NMOSD according to the 2015 diagnostic criteria. Patients from Argentina (n=77), Brazil (n=46), and Venezuela (n=17) were enrolled and classified into two groups as follows: with AD or without AD. Clinical, paraclinical (including aquaporin-4 antibodies (AQP4-ab) status), magnetic resonance imaging (MRI), and prognosis data were analyzed and compared. Kaplan-Meier (KM) and the Nelson-Aalen estimator analyses were performed to estimate both time and the cumulative hazard risk of disability reaching an EDSS≥4; and time for the first recurrence. RESULTS: Out of 140 patients, 33 (23.5%) patients had associated an AD at presentation. The most frequent associated AD was Hashimoto disease (n=10) followed by lupus (n=7) and Sjogren's syndrome (n=6). However, rituximab use (42.4% vs. 21.5%, p=0.02), female gender (82.2% vs. 100%, p=0.006), corticospinal lesions on MRI (0% vs. 12.5%, p=0.01) at onset, and positivity for antinuclear antibodies (21.2% vs. 48.4%, p=0.03) were significantly associated with NMOSD patients with AD in comparison to NMOSD patients without AD. No differences were found in other clinical and paraclinical aspects between groups. KM and Nelson-Aalen estimator analyses did not show differences between groups. CONCLUSION: NMOSD patients associated with AD were observed in 23.5%. In addition, NMOSD patients with and without associated AD were similar in most evaluated features.
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Neuromielitis Óptica , Síndrome de Sjögren , Humanos , Femenino , Neuromielitis Óptica/complicaciones , Neuromielitis Óptica/diagnóstico por imagen , Neuromielitis Óptica/epidemiología , Acuaporina 4 , Estudios Retrospectivos , Autoanticuerpos , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/epidemiologíaRESUMEN
BACKGROUND: The use of telemedicine has quickly increased during of the COVID-19 pandemic. Given that unmet needs and barriers to multiple sclerosis (MS) care have been reported, telemedicine has become an interesting option to the care of these patients. The objective of these consensus recommendations was to elaborate a guideline for the management of people with MS using telemedicine in order to contribute to an effective and high-quality healthcare. METHODS: A panel of Argentinean neurologist's experts in neuroimmunological diseases and dedicated to the diagnosis, management,and care of MS patients gathered virtually during 2021 and 2022 to conduct a consensus recommendation on the use of telemedicine in clinical practice in adult people with MS. To reach consensus, the methodology of "formal consensus RAND/UCLA Appropriateness method" was used. RESULTS: Recommendations were established based on relevant published evidence and expert opinion focusing on definitions, general characteristics and ethical standards, diagnosis of MS, follow-up (evaluation of disability and relapses of MS), identification and treatment of relapses, and finally disease-modifying treatments using telemedicine. CONCLUSION: The recommendations of this consensus would provide a useful guide for the proper use of telemedicine for the assessment, follow-up, management, and treatment of people with MS. We suggest the use of these guidelines to all the Argentine neurologists committed to the care of people with MS.
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COVID-19 , Esclerosis Múltiple , Telemedicina , Humanos , Adulto , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/terapia , Esclerosis Múltiple/epidemiología , Consenso , Pandemias , RecurrenciaRESUMEN
The objective was to evaluate time to reach an EDSS of 4, 6, and 7 in NMOSD and MOGAD patients included in the Argentinean MS and NMOSD registry (RelevarEM, NCT 03,375,177). METHODS: NMOSD patients diagnosed according to 2015 criteria and with MOGAD were identified. Patients with at least 3 years of follow-up and periodic clinical evaluations with EDSS outcomes were included. AQP4-antibody and MOG-antibody status was recorded, and patients were stratified as seropositive and seronegative for AQP4-antibody. EDSS of 4, 6, and 7 were defined as dependent variables. Log rank test was used to identify differences between groups. RESULTS: Registry data was provided for a total of 137 patients. Of these, seventy-five presented AQP4-ab-positive NMOSD, 45 AQP4-ab-negative NMOSD, and 11 MOGAD. AQP4-ab status was determined by cell-based assay (CBA) in 72% of NMOSD patients. MOG-ab status was tested by CBA in all cases. Mean time to EDSS of 4 was 53.6 ± 24.5 vs. 63.1 ± 32.2 vs. 44.7 ± 32 months in seropositive, seronegative NMOSD, and MOGAD, respectively (p = 0.76). Mean time to EDSS of 6 was 79.2 ± 44.3 vs. 75.7 ± 48.6 vs. 54.7 ± 50 months in seropositive, seronegative NMOSD, and MOGAD (p = 0.23), while mean time to EDSS of 7 was 86.8 ± 54 vs. 80.4 ± 51 vs. 58.5 ± 47 months in seropositive, seronegative NMOSD, and MOGAD (p = 0.39). CONCLUSION: No differences were observed between NMOSD (seropositive and seronegative) and MOGAD in survival curves.
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Neuromielitis Óptica , Humanos , Neuromielitis Óptica/epidemiología , Acuaporina 4 , Argentina/epidemiología , Glicoproteína Mielina-Oligodendrócito , Autoanticuerpos , Sistema de RegistrosRESUMEN
INTRODUCTION: Neuromyelitis optica spectrum disorders (NMOSD) are rare but often devastating neuroinflammatory autoimmune diseases of the central nervous system. Acute treatment is critically important and it should be initiated early and aggressively, as relapses result in severe residual disability. Acute treatments are still based on clinical experience and observational studies. The most commonly used treatments are steroids and plasmapheresis. Several new treatments to improve management and recovery after relapses in NMOSD are currently under investigation. AREAS COVERED: This review discusses current and the most recent advances in active development of phase II/III clinical trials for acute treatment options and therapeutic strategies that can help management improvement of NMOSD during a relapse. These treatments include bevacizumab, ublituximab and HBM9161. EXPERT OPINION: NMOSD relapses require prompt evaluation and timely treatment to restore function and mitigate disability. Timing is critical. Plasmapheresis showed better outcomes in terms of recovery when compared to high-dose intravenous methylprednisolone alone. Some groups suggest that plasmapheresis could be considered as an initial treatment approach in different clinical scenarios due to its higher effectiveness. Future research and/or real-world data will establish the advantages and disadvantages of these new treatments and define the appropriate patient profile.
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Neuromielitis Óptica , Adulto , Humanos , Neuromielitis Óptica/tratamiento farmacológico , RecurrenciaRESUMEN
BACKGROUND AND PURPOSE: Optic neuritis (ON) is often the initial symptom of neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein-associated disease (MOGAD). We aimed to compare the frequency and pattern of chiasmatic lesions in MOGAD-related ON (MOGAD-ON) and NMOSD-related ON (NMOSD-ON) using conventional brain imaging (magnetic resonance imaging [MRI]) in Latin America (LATAM). METHODS: We reviewed the medical records and brain MRI (≤30 days from ON onset) of patients with a first event of MOGAD-ON and NMOSD-ON. Patients from Argentina (n = 72), Chile (n = 21), Ecuador (n = 31), Brazil (n = 30), Venezuela (n = 10) and Mexico (n = 82) were included. Antibody status was tested using a cell-based assay. Demographic, clinical, imaging and prognostic (as measured by the Visual Functional System Score [VFSS] of the Expanded Disability Status Scale) data were compared. RESULTS: A total of 246 patients (208 NMOSD and 38 MOGAD) were included. No differences were found in gender and ethnicity between the groups. We observed chiasmatic lesions in 66/208 (31.7%) NMOSD-ON and in 5/38 (13.1%) MOGAD-ON patients (p = 0.01). Of these patients with chiasmatic lesions, 54/66 (81.8%) and 4/5 had associated longitudinally extensive optic nerve lesions, 45/66 (68%) and 4/5 had bilateral lesions, and 31/66 (47%) and 4/5 showed gadolinium-enhancing chiasmatic lesions, respectively. A positive correlation was observed between VFSS and presence of bilateral (r = 0,28, p < 0.0001), chiasmatic (r = 0.27, p = 0.0001) and longitudinally extensive lesions (r = 0,25, p = 0.0009) in the NMOSD-ON group, but no correlations were observed in the MOGAD-ON group. CONCLUSIONS: Chiasmatic lesions were significantly more common in NMOSD than in MOGAD during an ON attack in this LATAM cohort. Further studies are needed to assess the generalizability of these results.
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Neuromielitis Óptica , Neuritis Óptica , Acuaporina 4 , Autoanticuerpos , Humanos , América Latina , Imagen por Resonancia Magnética , Glicoproteína Mielina-Oligodendrócito , Neuritis Óptica/diagnóstico por imagenRESUMEN
Multiple sclerosis (MS) is currently thought to arise by interactions between genetic susceptibility and environmental factors. Infections in general trigger autoimmune responses causing clinical manifestations of disease. However, as a result of regulatory T (Treg)- and regulatory B (Breg)-cell induction, helminth infections tend to dampen disease activity. IL-35, the newest member of the IL-12 family, is an inhibitory cytokine composed of an EBI3ß chain subunit, and an IL-12p35 subunit. The aim of this study was to investigate the role of IL-35 during parasite infections occurring in individuals with MS. Numbers of IL-35-producing Breg cells are higher in CSF from helminth-infected than from uninfected MS subjects, a finding associated with decreased MRI disease activity. Interestingly, stimulation of CD19+ B cells with IL-35 promotes conversion of these cells to Breg cells producing both IL-35 and IL-10. Coculture of B cells from helminth-infected MS patients inhibits proliferation of Th1 and Th17 myelin peptide-specific T cells, as well as production of IFN-γ and IL-17. Following activation, CD4+ CD25+ Treg cells significantly upregulate expression of EBI3 and IL-12p35 mRNA. Furthermore, CD4+ CD25- T cells activated in the presence of IL-35 induce a population of cells with regulatory function, known as iTR35. Finally, B cells from normal individuals cultured in vitro in the presence of the helminth antigen SEA increase expression of the transcription BATF, IRF4 and IRF8, acquiring a pattern similar to that of IL-35 Breg cells. These data highlight the important immunoregulatory effects of IL-35 on both Breg and Treg cells, observed in helminth-infected MS subjects.
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Linfocitos B Reguladores/inmunología , Helmintiasis/inmunología , Interleucinas/metabolismo , Esclerosis Múltiple/complicaciones , Linfocitos T Reguladores/inmunología , Adulto , Animales , Linfocitos B Reguladores/metabolismo , Femenino , Helmintiasis/parasitología , Helmintos/inmunología , Helmintos/aislamiento & purificación , Interacciones Huésped-Parásitos , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/inmunología , Linfocitos T Reguladores/metabolismo , Células TH1/inmunología , Células Th17/inmunologíaRESUMEN
Neuromyelitis optica (NMO) is a chronic inflammatory autoimmune disease of the central nervous system (CNS) characterized by acute optic neuritis (ON) and transverse myelitis (TM). NMO is caused by a pathogenic serum IgG antibody against the water channel aquoporin 4 (AQP4) in the majority of patients. AQP4-antibody (AQP4-ab) presence is highly specific, and differentiates NMO from multiple sclerosis. It binds to AQP4 channels on astrocytes, triggering activation of the classical complement cascade, causing granulocyte, eosinophil, and lymphocyte infiltration, culminating in injury first to astrocyte, then oligodendrocytes followed by demyelination and neuronal loss. NMO spectrum disorder (NMOSD) has recently been defined and stratified based on AQP4-ab serology status. Most NMOSD patients experience severe relapses leading to permanent neurologic disability, making suppression of relapse frequency and severity, the primary objective in disease management. The most common treatments used for relapses are steroids and plasma exchange.Currently, long-term NMOSD relapse prevention includes off-label use of immunosuppressants, particularly rituximab. In the last 2 years however, three pivotal clinical trials have expanded the spectrum of drugs available for NMOSD patients. Phase III studies have shown significant relapse reduction compared to placebo in AQP4-ab-positive patients treated with satralizumab, an interleukin-6 receptor (IL-6R) inhibitor, inebilizumab, an antibody against CD19+ B cells; and eculizumab, an antibody blocking the C5 component of complement. In light of the new evidence on NMOSD pathophysiology and of preliminary results from ongoing trials with new drugs, we present this descriptive review, highlighting promising treatment modalities as well as auspicious preclinical and clinical studies.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Autoanticuerpos/metabolismo , Inmunosupresores/uso terapéutico , Neuromielitis Óptica/tratamiento farmacológico , Neuromielitis Óptica/metabolismo , Animales , Anticuerpos Monoclonales Humanizados/farmacología , Acuaporina 4/inmunología , Acuaporina 4/metabolismo , Astrocitos/efectos de los fármacos , Astrocitos/inmunología , Astrocitos/metabolismo , Autoanticuerpos/efectos de los fármacos , Autoanticuerpos/inmunología , Azatioprina/farmacología , Azatioprina/uso terapéutico , Ensayos Clínicos Fase III como Asunto/métodos , Humanos , Inmunosupresores/farmacología , Neuromielitis Óptica/inmunologíaRESUMEN
The objective of the present study was to identify the frequency of MS patients in Latin America (LATAM) that received the influenza vaccine during the most recent season and the reasons related to non-vaccination. Cross-sectional study between November and December 2020 in a large cohort of MS patients from LATAM. Patients responded about recommendation of receiving influenza vaccine and the use of it as well as reasons for not using the vaccine. Four hundred twelve MS patients were included in the analysis. 47.3% of patients were recommended to receive the vaccine from the treating physician. Nearly 54% of patients did not receive the influenza vaccine, and the most frequent cause was that it was neither recommended nor mentioned by the treating physician (27.4%). Female gender (OR = 2.3, 95%CI 1.4-3.8, p = 0.001) was associated with an increased risk of recommendation, while a progressive form of MS and higher EDSS decreased the risk (OR = 0.49, 95%CI 0.27-0.90, p = 0.023; OR = 0.65, 95%CI 0.55-0.97, p = 0.02, respectively). Despite the evidence to recommend the influenza vaccine in MS patients, a limited number of patients in clinical practice received such recommendation.
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Gripe Humana , Esclerosis Múltiple , Estudios Transversales , Femenino , Humanos , Gripe Humana/prevención & control , América Latina , Esclerosis Múltiple/tratamiento farmacológico , VacunaciónRESUMEN
BACKGROUND: Multiple sclerosis (MS), is an emergent disease in Latin America (LATAM), which raises substantial socioeconomic challenges to a region where most countries remain as economies in development. OBJECTIVE: To assess barriers to access and utilization of MS care services in a regional cohort survey. METHODS: We conducted a cross-sectional study based on a self-reported survey. Patients with MS (PwMS) completed this regional survey in 12 Latin American (LATAM) countries. PwMS were also divided into those with healthcare insurance (including certain local national social security programs) and those without healthcare insurance (treated at public institutions). RESULTS: We surveyed 1469 PwMS and identified significant regional differences in relation to access to complementary tests, rehabilitation services, and prescription of disease-modifying therapies (DMTs). Between 44.4% and 73.5% of PwMS were unemployed and nearly 50% had completed higher education. PwMS receiving care from the private sector reported greater access to imaging, DMTs, and fewer problems obtaining DMTs compared to those treated at public institutions. Multivariate analysis showed that lack of private insurance (OR = 2.21, p < 0.001), longer MS duration (OR = 1.02, p = 0.001), lower level of education (OR = 0.66, p = 0.009), and unemployment (OR = 0.73, p = 0.03) were independently associated with inappropriate delivery of DMTs. CONCLUSION: These findings suggest barriers to access and utilization of MS care services across LATAM are prevalent. We identified several factors predicting unmet healthcare needs in PwMS.
Asunto(s)
Esclerosis Múltiple , Estudios de Cohortes , Estudios Transversales , Humanos , América Latina/epidemiología , Esclerosis Múltiple/terapia , Encuestas y CuestionariosRESUMEN
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.