Frequency of cognitive impairment in patients with neuromyelitis optica spectrum disorder in Mexico.

Background: Between 29% and 67% of neuromyelitis optica spectrum disorder patients have cognitive alterations. Objective: To assess the frequency of cognitive impairment in patients with neuromyelitis optica spectrum disorder in Mexico using the Brief International Cognitive Assessment for Multiple Sclerosis. Methods: We evaluated 40 neuromyelitis optica spectrum disorder patients and 40 healthy controls from Mexico. Results: 28 (70.0%) patients with neuromyelitis optica spectrum disorder had cognitive impairment in two or more cognitive domains. Student´s T test showed statistically poor performance by neuromyelitis optica spectrum disorder patients compared to healthy controls on all three neuropsychological test scores. This significant difference was observed on the Symbols Digit Modalities Test (t = 8.875; p ≤ 0.001); California Verbal Learning Test-II memory (t = 10.418; p ≤ 0.001); and Brief Visuospatial Memory Test Revised (t = 6.123; p ≤ 0.001). Conclusions: This study showed that 70% of neuromyelitis optica spectrum disorder patients exhibited cognitive impairment in two or more cognitive domains. Determining the frequency of cognitive impairment will guide the decision of Neuropsychologists in planning cognitive rehabilitation across various domains.

Validation of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) in individuals with multiple sclerosis from Mexico.

BACKGROUND: Cognitive impairment is observed in 43-70 % of Multiple sclerosis (MS) patients. One of the most widely used batteries for cognitive assessment in this population is the Brief International Cognitive Assessment for MS (BICAMS). The objective of this study was to validate and assess the reliability of the BICAMS in a Mexican population with MS and to obtain and provide regression-based norms. METHODS: One hundred healthy controls (HCs) and 100 patients with multiple sclerosis participated in the present study, and groups were matched for age, years of education and sex. Subjects completed all three tests of the BICAMS. Test-retest measures were obtained from 30 patients to test reliability. RESULTS: The sample´s average age was 43.39 ± 6.03 years old, and the average years of education was 12.55 ± 2.52 years. Approximately 63 % of the participants were female. The groups did not differ in age, years of education, or sex. The MS group performed significantly worse than the HCs group on all three neuropsychological tests. A significant difference was observed for the SDMT (t = 10.166; p=<0.001), CVLT-II (t = 10.949; p=<0.001), and BVMT-R (t = 2.636; p = 0.009). For all comparisons, the effect size (d) for each test was calculated as follows: SDMT= 0.58 and CVLT-II= 0.61. The test-retest coefficients for each test were as follows: SDMT: r = 0.95; CVLT-II: r = 0.84; and BVMT-R = 0.81. CONCLUSION: The BICAMS can provide information on cognitive impairment in MS patients, and this information can be used by neuropsychologists for cognitive rehabilitation in different domains.

Risk factors associated with permanent disability in neuromyelitis optica spectrum disorders.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease of the central nervous system. In NMOSD, a relapse results in increased disability. OBJECTIVE: To assess risk factors associated with permanent disability (PD) in patients with neuromyelitis optica spectrum disorders (NMOSD). METHODS: We evaluated 34 cases (who developed permanent disability) and 33 controls. The assessment included the following variables: sociodemographic data and characteristics of the disease. Logistic regression analysis was performed to adjust variables associated with PD. RESULTS: fifty-one percent developed PD during follow-up; 15 (22%) developed permanent visual disability, 13 (19%) developed permanent motor disability and 6 (9%) were restricted to wheelchair. Factors associated with PD in the crude analysis were: age at onset ≥ 50 years (OR 3.95, 95% IC 1.12-13.94, p= 0.032), time from onset to diagnosis ≥ 12 months (OR 3.30, 95% IC 1.13-9.64, p= 0.029), time from onset to treatment ≥ 60 months (OR 4.16, 95% IC 1.03-16.85, p= 0.045), EDSS ≥ 4.0 at the first appointment (OR 3.21, 95% IC 1.18-8.76, p= 0.022) and severe relapses during disease evolution (OR 5.72, 95% IC 1.98-16.57, p= 0.001). Factors associated with PD in the adjusted analysis were: age at onset ≥ 50 years (OR 5.82, 95% IC 1.30-26.05, p= 0.021), time from onset to diagnosis ≥ 12 months (OR 5.43, 95% IC 1.47-20.08, p= 0.011) and severe relapses during disease evolution (OR 6.65, 95% IC 1.98-22.31, p= 0.002). CONCLUSION: Half of patients with NMOSD may develop PD during disease evolution. Age of onset ≥ 50 years, delay to diagnosis ≥12 months and initial EDSS ≥ 4.0 constitute the strongest risk factors for PD.

Effect of Rituximab Compared with Natalizumab and Fingolimod in Patients with Relapsing-Remitting Multiple Sclerosis: A Cohort Study.

The objective of this study was to evaluate the clinical files of patients with RRMS who started rituximab (RTX) compared with a second-line treatment (natalizumab (NTZ) or fingolimod (FTY)). This was a historical cohort study. We compared the effect according to the Expanded Disability Status Scale (EDSS) and the number of relapses in RRMS patients receiving these treatments after a mean period of 12 months. We found a statistically significant difference (p < 0.001) when comparing the EDSS scores and the annual relapse rates of patients receiving RTX with those receiving NTZ or FTY. This study is essential for our clinical practice, since patients with limited treatment options represent a challenge with regard to the management of their medical care. However, clinical trials and prospective studies with long follow-up periods are necessary to provide sufficient evidence on the efficacy of RTX and thus include this treatment in the therapeutic profile of patients with MS.

Neuromyelitis optica spectrum disorder in Western Mexico.

BACKGROUND: Neuromyelitis Optica Spectrum Disorders (NMOSD) are a group of inflammatory diseases of the Central Nervous System (CNS) that primarily affect the optic nerve and spinal cord, usually with a severe and relapsing course. Due to the scarce information in non-Caucasian populations, we aimed to describe incidence, prevalence, and main clinical characteristics of NMOSD in a defined region in Mexico. MATERIALS AND METHODS: Descriptive, retrospective analysis of all reported cases of NMOSD attended in the neurology department of the UMAE-HE, CMNO, IMSS, the biggest third level hospital in Western Mexico. We searched the electronic medical records of the hospital for patients with a diagnosis of NMO, and reviewed all cases to confirm if they fulfilled NMOSD 2015 diagnostic criteria. Data were collected through a structured form. We described adjusted incidence and prevalence according to the WHO method, for the IMSS affiliated total population in Jalisco state in 2019. RESULTS: 67 NMOSD patients were included in the analysis of clinical data, with a mean age at onset of symptoms of 36 years ((Rivera et al., 2008-65). Most patients were female (74.6%). 53 patients living in Jalisco by the end of 2019 were included in the analysis of prevalence and incidence. Adjusted prevalence was 0.71/100,000 (95% CI 0.55-0.92), while adjusted incidence was 1.87/1,000,000 person-years (95% CI 1.11-3.16). In the full cohort, the first symptom of NMOSD was optic neuritis in 49.3% of the patients, followed by transverse myelitis (23.9%) and area postrema syndrome (10.4%). 62 patients relapsed in a mean follow-up of 2 years (0-7). 5 patients with less than 6 months of follow up had not relapsed. 55.2% of the patients were AQP4-IgG +, 14.9% AQP4-IgG -, and 29.9% unknown status. CONCLUSIONS: Although NMOSD prevalence is similar to other reports around the world, incidence is higher than in Caucasian populations. We believe that this high incidence is related to an increased awareness of the disease in the era of new NMOSD treatments. Recurrent disease is very frequent in our cohort.

Practical issues concerning the use of Magnetic Resonance Imaging in Multiple Sclerosis in Latin America: Discussion from 16 centres on behalf of the Foro Latam EM Study Group.

MAGNIMS-CMSC-NAIMS consensus recommendations on the use of MRI in patients with multiple sclerosis have been recently published, and they have been fundamental for improving patient care. Implementation of these and previous MAGNIMS recommendations have not been established in many countries. Addressing the local limitations behind these difficulties is needed. A panel of 14 MS neurologists from 16 different reference centres from Chile, Argentina, Mexico, Colombia, Ecuador, Panamá, Perú and Brazil met to discuss the current situation regarding the use of MRI in MS including a) Access and availability, b) Standardized acquisition protocols and reports, and c) Multicentric research potential.

Brain MRI volumetric changes in the follow-up of patients with anti-NMDAr encephalitis.

INTRODUCTION: Autoimmune anti-NMDAr encephalitis is an antibody-mediated disorder characterized by psychiatric symptoms followed by decreased consciousness, dysautonomia and seizures. The pathophysiology of the disease is related to the internalization of NR1 subtype NMDA receptors and the dysfunction of structures where they are abundant (frontotemporal and insular regions). Some reports suggest the existence of cerebral atrophy in the follow-up of these patients, with conflicting evidence regarding its presence and usefulness as a marker of prognosis. METHODS: In a longitudinal, observational study, all patients with the diagnosis of definite anti-NMDAr autoimmune encephalitis with initial and control MRI studies were included. Conventional MR Brain acquisition was performed using a 3-Tesla Skyra MRI System. Automated brain segmental analysis was performed using the Volbrain volumetry system. The differences between baseline MRI volumetric characteristics and volumetric measures at follow-up was assessed. RESULTS: 25 patients were included (mean age 26.6, SD 9.6). 44% were females. The mean time between the studies was 24 (SD 21.4, 3-24) months. Significant volume loss was identified in the total brain volume (- 0.02%, p = 0.029), cerebellar volume (- 0.27%, p = 0.048) and brainstem volume (- 0.16%, p = 0.021). CONCLUSIONS: This study supports previous observations regarding volume loss in several brain regions of patients with antiNMDAr encephalitis. Further analyses are required to understand the role of treatment and severe clinical forms, as well as the relationship between volume loss and functional outcome.

Low levels of alpha-synuclein in peripheral tissues are related to clinical relapse in relapsing-remitting multiple sclerosis: a pilot cross-sectional study.

The protein alpha-synuclein (α-Syn) has been linked to neuroinflammatory conditions. We investigated whether the presence of α-Syn in peripheral tissues is a surrogate of brain inflammatory status in a small group of relapsing-remitting multiple sclerosis (RRMS) patients in a pilot cross-sectional study. Skin biopsies and peripheral blood were sampled from 34 healthy controls and 23 MS patients for measurement of α-Syn levels. Within the RRMS group 15 patients were in remission, and 8 patients were in the relapsing phase. The protein α-Syn was evaluated by means of immunohistochemistry and flow cytometry in skin and nucleated blood cells, respectively. In the skin, α-Syn levels were lower in relapsing MS than in the other groups, both in positive area (p = .021) and staining intensity (p = .004). In blood, the percentage of α-Syn-positive lymphocytes and monocytes were not statistically different between study groups. Moreover, the use of systemic steroids did not affect α-Syn positivity in MS-relapse patients. Finally, epidermic Langerhans cells did not stain positively for α-Syn. Overall, the levels of α-Syn positivity were lower in inflammatory relapse of RRMS patients when measured in peripheral tissues. We discuss the role of α-Syn levels in inflammation according to the obtained results.

Novel Point Mutations and A8027G Polymorphism in Mitochondrial-DNA-Encoded Cytochrome c Oxidase II Gene in Mexican Patients with Probable Alzheimer Disease.

Mitochondrial dysfunction has been thought to contribute to Alzheimer disease (AD) pathogenesis through the accumulation of mitochondrial DNA mutations and net production of reactive oxygen species (ROS). Mitochondrial cytochrome c-oxidase plays a key role in the regulation of aerobic production of energy and is composed of 13 subunits. The 3 largest subunits (I, II, and III) forming the catalytic core are encoded by mitochondrial DNA. The aim of this work was to look for mutations in mitochondrial cytochrome c-oxidase gene II (MTCO II) in blood samples from probable AD Mexican patients. MTCO II gene was sequenced in 33 patients with diagnosis of probable AD. Four patients (12%) harbored the A8027G polymorphism and three of them were early onset (EO) AD cases with familial history of the disease. In addition, other four patients with EOAD had only one of the following point mutations: A8003C, T8082C, C8201T, or G7603A. Neither of the point mutations found in this work has been described previously for AD patients, and the A8027G polymorphism has been described previously; however, it hasn't been related to AD. We will need further investigation to demonstrate the role of the point mutations of mitochondrial DNA in the pathogenesis of AD.

Envejecimiento y metabolismo: cambios y regulación

Los estudios sobre los efectos del envejecimiento en la fisiología y el metabolismo cada vez son más, uno de sus objetivos es contribuir a instrumentar programas para mejorar la calidad de vida y prevenir discapacidades en la vejez. Es de gran importancia mencionar que durante el envejecimiento se presenta una desaceleración natural del metabolismo, se produce una serie de cambios en la regulación de la energía, lo que contribuye a la pérdida de peso y grasa; estos cambios en la regulación de la ingesta calórica contribuyen en un aumento de la susceptibilidad al desequilibrio energético tanto positivo como negativo, lo cual va asociado a un deterioro en la salud. Sin embargo, el llegar a la vejez, no es una sentencia de muerte para el metabolismo, por el contrario, éste puede ser controlado mediante el mantenimiento de un estilo de vida activo, aunado a esto investigaciones han demostrado que el metabolismo puede ser regulado mediante el papel que desempeña un sistema de reloj sincronizado (ritmos biológicos), el cual a su vez es modulado por varias proteínas reguladoras; esta relación garantiza que las células funcionen correctamente y por tanto el mantenerse saludables. El objetivo de esta revisión es aportar información actualizada sobre la regulación metabolismo-energía y su relación con la gran variedad de componentes involucrados en el gasto energético que acompañan al envejecimiento; analizar la regulación de este sistema para mejorar la calidad de vida y mantener la salud en la vejez.

Aging and metabolism: changes and regulation. Studies about the effects of aging in the physiology and metabolism are increasingly, one of its objectives is to help implement programs to improve the quality of life and prevent disability in elderly. It is relevant to mention that, during aging, there is a natural metabolic deceleration, a series of changes in the regulation of energy are produced, which contributes to loss of weight and fat; the changes in the regulation of caloric intake contribute to increase the susceptibility to energy imbalance both positive and negative, which is associated with a deterioration in health. However, to grow old, is not a death sentence for metabolism, on the other hand, it can be controlled by maintaining an active lifestyle, coupled with this, research has shown that the metabolism can be regulated by a synchronized clock (circadian rhythms), which is mediated by regulatory proteins, this relationship ensures the proper functioning of the cells and therefore good health. The aim of this review is to provide updated information on the energy- metabolism-regulation and its relationship with the great variety of components involved in energy expenditure that accompany aging, to analyze the regulation of this system to improve the quality of life and maintenance of health in old age.

[Aging and metabolism: changes and regulation]. / Envejecimiento y metabolismo: cambios y regulación.

Studies about the effects of aging in the physiology and metabolism are increasingly, one of its objectives is to help implement programs to improve the quality of life and prevent disability in elderly. It is relevant to mention that, during aging, there is a natural metabolic deceleration, a series of changes in the regulation of energy are produced, which contributes to loss of weight and fat; the changes in the regulation of caloric intake contribute to increase the susceptibility to energy imbalance both positive and negative, which is associated with a deterioration in health. However, to grow old, is not a death sentence for metabolism, on the other hand, it can be controlled by maintaining an active lifestyle, coupled with this, research has shown that the metabolism'can be regulated by a synchronized clock (circadian rhythms), which is mediated by regulatory proteins, this relationship ensures the proper functioning of the cells and therefore good health. The aim of this review is to provide updated information on the energy- metabolism-regulation and its relationship with the great variety of components involved in energy expenditure that accompany aging, to analyze the regulation of this system to improve the quality of life and maintenance of health in old age.