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.

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.

Consensus recommendations for the diagnosis and treatment of primary progressive multiple sclerosis in Latin America.

Despite the availability of a large amount of information regarding the management and care of relapsing remitting multiple sclerosis (RRMS) patients, there is scant information about recommendations on how to care for primary progressive MS (PPMS) patients. The objective of this study was to review how PPMS patients should be assessed and cared for in Latin America (LATAM). METHODS: A panel of neurology experts from LATAM dedicated to the diagnosis and care of MS patients gathered virtually during 2017 and 2018 to carry out a consensus recommendation on the diagnosis and treatment of PPMS patients in LATAM. To achieve consensus, the methodology of "formal consensus-RAND/UCLA method" was used. RESULTS: Recommendations focused on disease management, and specific and symptomatic disease treatment were determined. The main consensus was that the 2017 McDonald criteria should be used for diagnosis but that the exclusion of regional diseases is strongly recommended; that specific considerations should be taken regarding immunotherapy treatments used in MS due to the scarce evidence available; and that a general approach that considers symptomatic treatment and rehabilitation should be performed in affected patients to improve their status. CONCLUSIONS: The recommendations of these consensus guidelines attempt to optimize the health care and management of PPMS patients in LATAM.

Mediational Model of Multiple Sclerosis Impairments, Family Needs, and Caregiver Mental Health in Guadalajara, Mexico.

Individuals with multiple sclerosis (MS), especially those living in Latin America, often require assistance from family caregivers throughout the duration of the disease. Previous research suggests that family caregivers may experience positive and negative outcomes from providing care to individuals with MS, but few studies have examined the unmet needs of individuals providing care to family members with MS and how these unmet needs may mediate the relationship between MS symptoms and caregiver mental health. The current study examined the relationships among MS impairments (functional, neurological, cognitive, behavioral, and emotional), unmet family needs (household, informational, financial, social support, and health), and caregiver mental health (satisfaction with life, anxiety, burden, and depression) in a sample of 81 MS caregivers from Guadalajara, Mexico. A structural equation model demonstrated the mediational effect of unmet family needs on the relationship between MS impairments and caregiver mental health. These findings suggest that intervention research on MS caregivers in Latin America may consider focusing on caregiver mental health problems by addressing unmet family needs and teaching caregivers ways to manage the impairments of the individual with MS.

Effect of fish and olive oil on mitochondrial ATPase activity and membrane fluidity in patients with relapsing-remitting multiple sclerosis treated with interferon beta 1-b.

BACKGROUND: Multiple sclerosis (MS) is an inflammatory disease of the central nervous system associated with increased oxidative stress (OS) and mitochondrial alterations. Fish oil consumption has neuroprotective, antioxidant and anti-inflammatory effects in patients with relapsing-recurrent MS (RR-MS). OBJECTIVE: To evaluate changes in the hydrolytic activity of ATP synthase and mitochondrial membrane fluidity in patients with RR-MS who receive fish oil or olive oil as a dietary supplement. METHODS: Clinical, controlled, randomized, double-blind trial. Patients consumed fish oil or olive oil for one year. The hydrolytic activity of ATPase and the fluidity of the mitochondrial membrane of platelets were quantified. RESULTS: In patients with RR-MS, a decrease in the fluidity of mitochondrial membranes and an increase in the hydrolytic activity of ATP synthase was observed in comparison with healthy controls. After 6 or 9 months of treatment with fish oil or olive oil, respectively, these values were normalized. CONCLUSION: The consumption of fish oil and olive oil increases the fluidity of the mitochondrial membranes and decreases the catabolic activity of ATP synthase in platelets from patients with RR-MS.

Effect of fish and olive oil on mitochondrial ATPase activity and membrane fluidity in patients with relapsing-remitting multiple sclerosis treated with interferon beta 1-b / Efecto del aceite de pescado en la actividad hidrolítica de la ATPasa y en la fluidez de la membrana mitocondrial en pacientes con esclerosis múltiple remitente-recurrente tratados con interferón beta 1-b

Background: Multiple sclerosis (MS) is an inflammatory disease of the central nervous system associated with increased oxidative stress (OS) and mitochondrial alterations. Fish oil consumption has neuroprotective, antioxidant and anti-inflammatory effects in patients with relapsing-recurrent MS (RR-MS). Objective: To evaluate changes in the hydrolytic activity of ATP synthase and mitochondrial membrane fluidity in patients with RR-MS who receive fish oil or olive oil as a dietary supplement. Methods: Clinical, controlled, randomized, double-blind trial. Patients consumed fish oil or olive oil for one year. The hydrolytic activity of ATPase and the fluidity of the mitochondrial membrane of platelets were quantified. Results: In patients with RR-MS, a decrease in the fluidity of mitochondrial membranes and an increase in the hydrolytic activity of ATP synthase was observed in comparison with healthy controls. After 6 or 9 months of treatment with fish oil or olive oil, respectively, these values were normalized. Conclusion: The consumption of fish oil and olive oil increases the fluidity of the mitochondrial membranes and decreases the catabolic activity of ATP synthase in platelets from patients with RR-MS (AU)

Introducción: la esclerosis multiple (EM) es una enfermedad inflamatoria del sistema nervioso central asociada con estrés oxidativo (EO) y alteraciones mitocondriales. El aceite de pescado tiene efectos neuroprotectores, antioxidantes y antiinflamatorios en pacientes con EM remitente-recurrente (EM-RR). Objetivo: evaluar los cambios en la actividad hidrolítica de la ATPasa y de la fluidez de membrana mitocondrial en pacientes con EM-RR que reciben aceite de pescado o aceite de oliva como suplemento alimenticio. Métodos: ensayo clínico, controlado, aleatorizado, doble ciego. Los pacientes consumieron aceite de pescado o aceite de oliva durante un año. Se cuantifico la actividad hidrolítica de la ATPasa y la fluidez de la membrana mitocondrial de plaquetas. Resultados: en pacientes con EM-RR hay una disminución de la fluidez de las membranas mitocondriales y un incremento de la actividad hidrolítica de la ATPasa en comparación con controles sanos. Después de 6 y 9 meses de tratamiento con aceite de oliva y de aceite de pescado, respectivamente, los valores se normalizaron y se mantuvieron así hasta el fin del estudio. Conclusión: el consumo de aceite de pescado y aceite de oliva incrementan la fluidez de membrana y disminuye la actividad catabólica de la ATP sintasa en pacientes con EM-RR (AU)

Environmental noise exposure modifies astrocyte morphology in hippocampus of young male rats.

BACKGROUND: Chronic exposure to noise induces changes on the central nervous system of exposed animals. Those changes affect not only the auditory system but also other structures indirectly related to audition. The hippocampus of young animals represents a potential target for these effects because of its essential role in individuals' adaptation to environmental challenges. OBJECTIVE: The aim of the present study was to evaluate hippocampus vulnerability, assessing astrocytic morphology in an experimental model of environmental noise (EN) applied to rats in pre-pubescent stage. MATERIALS AND METHODS: Weaned Wistar male rats were subjected to EN adapted to the rats' audiogram for 15 days, 24 h daily. Once completed, plasmatic corticosterone (CORT) concentration was quantified, and immunohistochemistry for glial fibrillary acidic protein was taken in hippocampal DG, CA3, and CA1 subareas. Immunopositive cells and astrocyte arborizations were counted and compared between groups. RESULTS: The rats subjected to noise exhibited enlarged length of astrocytes arborizations in all hippocampal subareas. Those changes were accompanied by a marked rise in serum CORT levels. CONCLUSIONS: These findings confirm hippocampal vulnerability to EN and suggest that glial cells may play an important role in the adaptation of developing the participants to noise exposure.

Effect of fish oil on glutathione redox system in multiple sclerosis.

UNLABELLED: Multiple sclerosis (MS) is a chronic, inflammatory and autoimmune disease of the central nervous system. Dysregulation of glutathione homeostasis and alterations in glutathione-dependent enzyme activities are implicated in the induction and progression of MS. Evidence suggests that Omega-3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory, antioxidant and neuroprotective effects. The aim of the present work was to evaluate the effect of fish oil on the activity of glutathione reductase (GR), content of reduced and oxidized glutathione, and GSH/GSSG ratio in MS. 50 patients with relapsing-remitting MS were enrolled. The experimental group received orally 4 g/day of fish oil for 12 months. Fish oil supplementation resulted in a significant increase in n-3 fatty acids and a decrease n-6 fatty acids. No differences in glutathione reductase activity, content of reduced and oxidized glutathione, and GSH/GSSG ratio were found. CONCLUSION: Glutathione reductase activity was not significantly different between the groups; however, fish oil supplementation resulted in smaller increase in GR compared with control group, suggesting a possible effect on antioxidant defence mechanisms.

A 2-year observational study of patients with relapsing-remitting multiple sclerosis converting to glatiramer acetate from other disease-modifying therapies: the COPTIMIZE trial.

Studies suggest that patients with relapsing-remitting multiple sclerosis (RRMS) who do not benefit from other disease-modifying treatments (DMTs) may benefit from converting to glatiramer acetate (GA). COPTIMIZE was a 24-month observational study designed to assess the disease course of patients converting to GA 20 mg daily from another DMT. Eligible patients had converted to GA and had received prior DMT for 3-6 months, depending on the reasons for conversion. Patients were assessed at baseline and at 6, 12, 18, and 24 months. In total, 672 patients from 148 centers worldwide were included in the analysis. Change of therapy to GA was prompted primarily by lack of efficacy (53.6 %) or intolerable adverse events (AEs; 44.8 %). Over a 24-month period, 72.7 % of patients were relapse free. Mean annual relapse rate decreased from 0.86 [95 % confidence interval (CI) 0.81-0.91] before the change to 0.32 (95 % CI 0.26-0.40; p < 0.0001) at last observation, while the progression of disability was halted, as the Kurtzke Expanded Disability Status Scale (EDSS) scores remained stable. Patients improved significantly (p < 0.05) on measures of fatigue, quality of life, depression, and cognition; mobility scores remained stable. The results indicate that changing RRMS patients to GA is associated with positive treatment outcomes.

Prevalence of Dementia, Emotional State and Physical Performance among Older Adults in the Metropolitan Area of Guadalajara, Jalisco, Mexico.

Background. Dementia affects memory, thinking, language, judgment, and behavior. Depression, is common in older adults with dementia. The concomitance of dementia and depression increases disability with impaired activities of daily living (ADL), increasing the chances of institutionalization and mortality. Methods. Cross-sectional study of a population 60 years and older who live in the State of Jalisco, Mexico. A total of 1142 persons were assessed regarding their cognitive function, emotional state, and physical performance. Door-to-door interview technique was assigned in condition with multistage probability random sampling. Cognitive function, depression and functional disability were assessed by applying standardized Minimental State Examination (Folstein), Geriatric Depression Scale, and the Katz index, respectively. Diagnosis of dementia was performed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, the Fourth Edition. Data were analyzed using SPSS software. Results. Prevalence of demency was 9.5% (63.35% women, and 36.7% men). Demency was associated with being woman, being older than 70 years, low level of education, not having the economic benefit of retirement, being single or living without a partner, low level of education, suffering from depression and have functional disability in ADL. Conclusion. Dementia is more common in women and is related to depression and disability.

Immunology and oxidative stress in multiple sclerosis: clinical and basic approach.

Multiple sclerosis (MS) exhibits many of the hallmarks of an inflammatory autoimmune disorder including breakdown of the blood-brain barrier (BBB), the recruitment of lymphocytes, microglia, and macrophages to lesion sites, the presence of multiple lesions, generally being more pronounced in the brain stem and spinal cord, the predominantly perivascular location of lesions, the temporal maturation of lesions from inflammation through demyelination, to gliosis and partial remyelination, and the presence of immunoglobulin in the central nervous system and cerebrospinal fluid. Lymphocytes activated in the periphery infiltrate the central nervous system to trigger a local immune response that ultimately damages myelin and axons. Pro-inflammatory cytokines amplify the inflammatory cascade by compromising the BBB, recruiting immune cells from the periphery, and activating resident microglia. inflammation-associated oxidative burst in activated microglia and macrophages plays an important role in the demyelination and free radical-mediated tissue injury in the pathogenesis of MS. The inflammatory environment in demyelinating lesions leads to the generation of oxygen- and nitrogen-free radicals as well as proinflammatory cytokines which contribute to the development and progression of the disease. Inflammation can lead to oxidative stress and vice versa. Thus, oxidative stress and inflammation are involved in a self-perpetuating cycle.

Cost of care according to disease-modifying therapy in Mexicans with relapsing-remitting multiple sclerosis.

Limited data exist on the costs of care of patients with multiple sclerosis (MS) in low- to middle-income nations. The purpose of this study was to describe the economic burden associated with care of Mexican patients with relapsing-remitting MS in a representative sample of the largest institution of the Mexican public healthcare system. We analysed individual data of 492 patients (67% women) with relapsing-remitting MS registered from January 2009 to February 2011 at the Mexican Social Security Institute. Direct costs were measured about the use of diagnostic tests, disease-modifying therapies (DMTs), symptoms control, medical consultations, relapses, intensive care and rehabilitation. Four groups were defined according to DMT alternatives: (1) interferon beta (IFNß)-1a, 6 million units (MU); (2) IFNß-1a, 12MU; (3) IFNß-1b, 8MU; and (4) glatiramer acetate. All patients received DMTs for at least 1 year. The most frequently used DMT was glatiramer acetate (45.5%), followed by IFNß-1a 12MU (22.6%), IFNß-1b 8MU (20.7%), and IFNß-1a 6MU (11.2%). The mean cost of a specialised medical consultation was €74.90 (US $107.00). A single relapse had a mean total cost of €2,505.97 (US $3,579.96). No differences were found in annualised relapse rates and costs of relapses according to DMT. However, a significant difference was observed in total annual costs according to treatment groups (glatiramer acetate being the most expensive), mainly due to differences in unitary costs of alternatives. From the public institutional perspective, when equipotent DMTs are used in patients with comparable characteristics, the costs of DMTs largely determine the total expenses associated with care of patients with relapsing-remitting MS in a middle-income country.

Neural restrictive silencer factor and choline acetyltransferase expression in cerebral tissue of Alzheimer's Disease patients: A pilot study.

Decreased Choline Acetyltransferase (ChAT) brain level is one of the main biochemical disorders in Alzheimer's Disease (AD). In rodents, recent data show that the CHAT gene can be regulated by a neural restrictive silencer factor (NRSF). The aim of the present work was to evaluate the gene and protein expression of CHAT and NRSF in frontal, temporal, entorhinal and parietal cortices of AD patient brains. Four brains from patients with AD and four brains from subjects without dementia were studied. Cerebral tissues were obtained and processed by the guanidine isothiocyanate method for RNA extraction. CHAT and NRSF gene and protein expression were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. CHAT gene expression levels were 39% lower in AD patients as compared to the control group (p < 0.05, U test). ChAT protein levels were reduced by 17% (p = 0.02, U test). NRSF gene expression levels were 86% higher in the AD group (p = 0.001, U test) as compared to the control group. In the AD subjects, the NRSF protein levels were 57% higher (p > 0.05, U test) than in the control subjects. These findings suggest for the first time that in the brain of AD patients high NRSF protein levels are related to low CHAT gene expression levels.

Prevalence of Cognitive Impairment and Depression among a Population Aged over 60 Years in the Metropolitan Area of Guadalajara, Mexico.

Background. Cognitive impairment is an important clinical issue among elderly patients with depression and has a more complex etiology because of the variable rate of neurodegenerative changes associated with depression. The aim of the present work was to examine the prevalence of cognitive impairment and depression in a representative sample of adults aged ≥60 years. Methods. The presented work was a cross-sectional study on the prevalence of cognitive impairment and depression. Door-to-door interview technique was assigned in condition with multistage probability random sampling to obtain subjects that represent a population of the Guadalajara metropolitan area (GMA), Mexico. Cognitive function and depression were assessed by applying standardized Mini-Mental State Examination of Folstein (MMSE) and the Geriatric Depression Scale (GDS), respectively. Results. Prevalence of cognitive impairment was 13.8% (14.5% women, 12.6% men); no significant differences by gender and retired or pensioner were found. Prevalence of depression was 29.1% (33.6% women, 21.1% men); no significant differences by retired or pensioner were found. Cognitive impairment was associated with depression (OR = 3.26, CI 95%, 2.31-4.60). Prevalence of cognitive impairment and depression is associated with: being woman, only in depression being older than 75 years being married, and a low level of education. Conclusion. Cognitive impairment and depression are highly correlated in adults aged ≥60.

Effects of risk genes on BOLD activation in presymptomatic carriers of familial Alzheimer's disease mutations during a novelty encoding task.

Prior functional magnetic resonance imaging (fMRI) studies have found increased activity-related blood oxygen level-dependent (BOLD) signal in cognitively normal persons at genetic risk for Alzheimer's disease (AD). This has been interpreted as a compensatory response to incipient AD pathology. We studied the effects of fully penetrant familial Alzheimer's disease (FAD) mutations and apolipoprotein E (APOE) genotype on BOLD fMRI during a novelty encoding task in presymptomatic subjects. Twenty-three Mexican or Mexican-American persons at-risk for inheriting FAD mutations performed a block design novelty encoding task, and activation exhibited by FAD mutation carriers (MCs) was contrasted with that of noncarriers (NCs) and among APOE genotype groups. FAD MCs (n = 14) showed decreased BOLD activation in the anterior cingulate gyrus relative to 9 NCs. No increased activation was seen in MCs relative to NCs. Four APOE ε3/4 carriers demonstrated increased BOLD signal compared with 14 ε3/3 carriers in the occipital and perisylvian cortices bilaterally. There were no areas where ε3/3 carriers activated more than ε3/4 carriers. Our findings of increased fMRI activation associated with APOE genotype but not with FAD mutations suggest that APOE exerts an effect on the BOLD signal that is not readily explained as a compensatory phenomenon.

Tratamiento de la candiduria en pacientes en estado crítico: estudio comparativo entre fluconazol vía oral y anfotericina B en irrigación / Treatment of candiduria in the critically ill: comparative study between oral fluconazole and irrigated amphotericin B

La participación de origen micótico en el desarrollo de infecciones nosocomiales se ha incrementado de 1980 a 1990 de 6 a 10.4 por ciento en todos los sitios de infección. Para el tracto urinario la incidencia se ha elevado de 6.7 a 18.7 por ciento. Se compara la eficiencia y seguridad del fluconazol contra anfotericina B para erradicación de candiduria en pacientes en estado crítico: 1) fluconazol, 100 mg vía oral o vía sonda nasogástrica cada 12 horas, 2) anfotericina B, 25 mg en 1000 mL en solución de agua bidestilada para irrigación vesical continua cada 24 horas. Se trataron 15 pacientes por grupo. No hay diferencia entre ambas modalidades terapéuticas en el tiempo de erradicación de la funguria (p<0.05 t de student). En el grupo de irrigación vesical continua se presentó 20 por ciento de espisodios de fungemia, con deterioro clínico y aumento en la permanencia en la unidad. No se demostraron efectos colaterales en ninguna de las modalidades terapéuticas. Ante la posibilidad de diseminación o de estar tratando tópicamente un problema sistémico no se recomienda en este grupo de pacientes el empleo de anfotericina B en irrigación