Socioeconomic, health-care access and clinical determinants of disease severity in Multiple Sclerosis in Chile.

BACKGROUND: MS severity may be affected by genetic, patient-related, disease-related and environmental factors. Socioeconomic status, including income and healthcare access, amongst others, may also have a role in affecting diagnostic delay or therapy prescription. In Chile, two main healthcare systems exist, public-healthcare and private-healthcare, nonetheless universal care laws (e.g., access to High Efficacy Therapy-HET), including both systems, have been recently enacted for people with MS. OBJECTIVE: To assess the role of Socioeconomic Conditions (SEC), clinical variables and public health policies on the impact of disease severity of MS patients in Chile. METHODS: Multicentric, observational, cross-sectional study including patients from two reference centres (1 national reference centre from the private-health system and 1 regional reference centre from the public-health system). SEC and clinical variables included healthcare insurance (private or public), subclassification of health insurance according to monthly income, sex, age at onset, diagnostic delay, disease duration, diagnosis before HET law (as a proxy of HET delay), and current HET treatment. Progression Index (PI), EDSS ≥6.0 and Progressive MS diagnosis were used as outcome measures. Multivariable binary logistic regression was performed. RESULTS: We included 604 patients (460 private-health, 144 public-health), 67% women, 100% white/mestizo, 88% RRMS, mean age 42±12 years, mean age at onset 32±11 years, mean disease duration 10±6 years, median diagnostic delay 0 (0-34) years, 86% currently receiving any DMT, 55% currently receiving HET, median EDSS at last visit of 2.0 (0-10), and median PI 0.17 (0-4.5). Lower monthly income was associated with higher EDSS and higher PI. In the multivariable analysis, public-healthcare (OR 10.2), being diagnosed before HET-law (OR 4.89), longer diagnostic delay (OR 1.26), and older age at onset (OR 1.05) were associated with a higher risk of PI>0.2, while current HET (OR 0.39) was a protective factor. Diagnosis before HET-law (OR 7.59), public-healthcare (OR 6.49), male sex (OR 2.56), longer disease duration (OR 1.2) and older age at onset (OR 1.1) were associated with a higher risk of Progressive MS. Public-healthcare (OR 5.54), longer disease duration (OR 1.14) and older age at onset (OR 1.08) were associated with a higher risk of EDSS ≥6.0 while current treatment with HET had a trend as being a protective factor (OR 0.44, p = 0.05). CONCLUSION: MS severity is impacted by non-modifiable factors such as sex and age at onset. Interventions focused on shortening diagnostic delay and encouraging early access to high-efficacy therapies, as well as initiatives that may reduce the disparities inherent to lower socioeconomic status, may improve outcomes in people with MS.

[Neuromyelitis optica spectrum disorders: profile of a cohort according to the 2015 diagnostic criteria]. / Espectro de neuromielitis optica: descripcion de una cohorte segun los criterios diagnosticos de 2015.

INTRODUCTION: The new 2015 criteria for neuromyelitis optica spectrum disorders (NMOSD) have been recently incorporated in the study of different international cohorts. AIM: To describe clinical-radiological characteristics and prognostic factors in patients with NMOSD according to the 2015 criteria. PATIENTS AND METHODS: Retrospective analysis of 36 patients diagnosed with NMOSD according to serologic AQP4 status (positive, negative, unknown and negative + unknown). Clinical and radiological characteristics were compared and possible disability prognostic factors were evaluated. RESULTS: AQP4 were positive in 7 patients, negative in 12 and unknown in 17. Age of presentation was 36.6 ± 16 years, with higher female proportion (4:1). Mean disease duration was 7.4 ± 7.6 years. Most frequent presenting symptoms were acute myelitis (61%), optic neuritis (33%) and area postrema syndrome (11%). Most frequent MRI lesion was longitudinally extensive transverse myelitis (75%). All patients received acute treatment during attacks, and preventive treatment was used in 81% (azathioprine and rituximab mostly prescribed). Median EDSS was 2.0 at the end of follow-up. No differences were observed in any of the variables comparing serologic status. Age of first attack was prognostic, with direct correlation with EDSS. First attack in < 30 years was protective, meanwhile > 50 years old patients had increased risk of disability. CONCLUSIONS: The 2015 criteria allow the description and classification of NMOSD patients within different cohorts. Age of first attack seems to be a prognostic factor for developing disability.

TITLE: Espectro de neuromielitis optica: descripcion de una cohorte segun los criterios diagnosticos de 2015.Introduccion. Los nuevos criterios diagnosticos de 2015 del espectro de neuromielitis optica (NMO) estan comenzando a utilizarse en diferentes poblaciones en el mundo. Objetivo. Describir las caracteristicas clinicorradiologicas y pronosticas de pacientes diagnosticados de NMO con los criterios de 2015. Pacientes y metodos. Analizamos retrospectivamente 36 pacientes diagnosticados de NMO con los actuales criterios. Se generaron cuatro grupos segun la serologia de antiacuaporina 4 (positivos, negativos, desconocidos y negativos mas desconocidos agrupados). Se compararon sus caracteristicas clinicorradiologicas y se evaluaron posibles variables pronosticas de discapacidad. Resultados. Encontramos siete pacientes seropositivos, 12 negativos y 17 desconocidos. La edad de inicio fue de 36 ± 16 años, con mayor proporcion de mujeres (4 a 1). La duracion de la enfermedad fue de 7,4 ± 7,6 años. Los sintomas iniciales mas frecuentes fueron mielitis (61%), neuritis optica (33%) y sindrome del area postrema (11%). La lesion mas frecuente en la resonancia magnetica fue la mielitis longitudinalmente extensa (75%). Todos los pacientes recibieron tratamiento agudo, y el preventivo se utilizo en el 81%; la azatioprina y el rituximab fueron los que mas se usaron. La mediana de la Expanded Disability Status Scale (EDSS) fue de 2 al final del seguimiento. No hubo diferencias significativas en las variables clinicorradiologicas entre los distintos grupos de pacientes. La edad de inicio fue pronostica y presenta correlacion directa con la EDSS. El inicio antes de los 30 años fue protector y, despues de los 50 años, un factor de riesgo para mayor discapacidad. Conclusiones. Los actuales criterios permiten describir diferentes cohortes. La edad de inicio parece ser un factor pronostico para desarrollar discapacidad.

Reduction of beta-amyloid-induced neurotoxicity on hippocampal cell cultures by moderate acidosis is mediated by transforming growth factor beta.

Progression of Alzheimer's disease (AD) is associated with chronic inflammation and microvascular alterations, which can induce impairment of brain perfusion because of vascular pathology and local acidosis. Acidosis can promote amyloidogenesis, which could further contribute to neurodegenerative changes. Nevertheless, there is also evidence that acidosis has neuroprotective effects in hypoxia models. Here we studied the effect of moderate acidosis on beta-amyloid (Abeta)-mediated neurotoxicity. We evaluated morphological changes, cell death, nitrite production and reductive metabolism of hippocampal cultures from Sprague-Dawley rats exposed to Abeta under physiological (pH 7.4) or moderate acidosis (pH 7.15-7.05). In addition, because transforming growth factor beta (TGFbeta) 1 is neuroprotective and is induced by several pathophysiological conditions, we assessed its presence at the different pHs. The exposure of hippocampal cells to Abeta induced a conspicuous reduction of neurites' arborization, as well as increased neuronal death and nitric oxide production. However, Abeta neurotoxicity was significantly attenuated when hippocampal cultures were kept at pH 7.15-7.05, showing a 68% reduction on lactate dehydrogenase release compared with cultures exposed to Abeta at pH 7.4 (P<0.01). Similarly, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide reduction increased 3.5-fold (P<0.05), and Abeta-induced nitrite production was reduced by 65% when exposed to moderate acidosis compared with basal pH media (P<0.05). At the same time, moderate acidosis decreased intracellular TGFbeta1 precursor (latency associated protein-TGFbeta1) and increased up to fourfold TGFbeta1 bioactivity, detecting a 43% increase in the active TGFbeta levels in cultures exposed to Abeta and moderate acidosis. Inhibition of TGFbeta signaling abolished the neuroprotective effect of moderate acidosis. Our results show that moderate acidosis protected hippocampal cells from Abeta-mediated neurotoxicity through the increased activation and signaling potentiation of TGFbeta.