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Background: The relationship between serum glycoprotein syndecan-1 and disease activity in rheumatoid arthritis (RA) is still unknown. This study aimed to evaluate whether serum syndecan-1 concentrations are associated with moderate/severe disease activity. Methods: Study Design: This was a cross-sectional study. Seventy-five adult women with RA were classified into (a) moderate/severe RA based on the disease activity score, using the erythrocyte sedimentation rate (DAS28-ESR ≥ 3.2, n = 50), and (b) RA in remission (DAS28-ESR < 2.6, n = 25). Twenty-five healthy women were taken as the reference group. Syndecan-1 levels were determined using enzyme-linked immunosorbent assay (ELISA). High values of serum syndecan-1 levels (≥24 ng/mL) were used to identify the utility values of this biomarker. Results: The patients with RA had higher levels of syndecan-1 than the controls (p < 0.001). RA patients with active disease had higher syndecan-1 levels than RA patients in remission (57.6 vs. 23.5 ng/mL, respectively; p = 0.002). High syndecan-1 concentrations demonstrated the following utility values for identifying disease activity: sensitivity, 84% (95%CI: 71-93); specificity, 52% (95%CI: 31-72); positive predictive value, 78% (95%CI: 70-84); and negative predictive value, 62% (95%CI: 44-77). Conclusions: High syndecan-1 levels have good sensitivity and positive predictive value for identifying disease activity; however, their specificity is limited. Future prospective studies are needed to assess whether syndecan-1 levels can predict treatment failure in RA.

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Background: Rheumatoid arthritis (RA) in elderly population represents a challenge for physicians in terms of therapeutic management. Methotrexate (MTX) is the first-line treatment among conventional synthetic-disease-modifying anti-rheumatic drugs (cs-DMARDs); however, it is often associated with adverse events (AEs). Therefore, the objective of this study was to identify the incidence and risk factors of MTX discontinuation due to AEs in elderly patients with RA in a long-term retrospective cohort study. Methods: Clinical sheets from elderly RA patients taking MTX from an outpatient rheumatology consult in a university centre were reviewed. To assess MTX persistence, we used Kaplan-Meir curves and Cox regression models to identify the risk of withdrawing MTX due to adverse events. Results: In total, 198 elderly RA patients who reported using MTX were included. Of them, the rates of definitive suspension of MTX due to AEs were 23.0% at 5 years, 35.6% at 10 years and 51.7% at 15 years. The main organs and system involved were gastrointestinal (15.7%) and mucocutaneous (3.0%). Factors associated with withdrawing MTX due to AEs were MTX dose ≥ 15 mg/wk (adjusted HR: 2.46, 95% CI: 1.22-4.96, p = 0.012); instead, the folic acid supplementation was protective for withdrawal (adjusted HR: 0.28, 95% CI: 0.16-0.49, p < 0.001). Conclusions: Higher doses of MTX increase the risk of withdrawals in elderly RA, while folic acid supplementation reduces the risk. Therefore, physicians working in therapeutic management for elderly patients using MTX must focus on using lower MTX doses together with the concomitant prescription of folic acid.

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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.

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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.

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Cognition is a set of brain processes that allow the individual to interact with their environment. Multiple sclerosis (MS) is a chronic inflammatory disease that affects the cerebral white matter of the brain cortex and spinal cord, leading to cognitive impairment (CI) in 40-60% of the patients. Many studies have determined that CI is linked to genetic risk factors. We aimed to evaluate the association between BDNF gene rs6265 polymorphism and cognitive impairment in Mexican patients with MS by performing a case-control study. Mestizo-Mexican patients diagnosed with MS based on McDonald's criteria were enrolled. Cases were MS patients with CI (n = 31) while controls were MS patients without CI (n = 31). To measure cognitive functioning in MS patients, a neuropsychological screening battery for MS (NSB-MS) was used. Genotyping of the rs6265 gene variant was performed using quantitative real-time PCR (qPCR) with TaqMan probes. The results showed no statistically significant differences in sociodemographic and disease variables between case and control groups. qPCR analysis showed that there were 68% Val/Val wild-type homozygotes, 29% Val/Met polymorphic heterozygotes, and 3% Met/Met polymorphic homozygotes. The presence of BDNF gene rs6265 polymorphism showed an increased probability (3.6 times) of global cognitive impairment.

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Multiple sclerosis (MS) is a chronic and demyelinating disease with an autoimmune origin, which leads to neurodegeneration and progressive disability. Approximately 30 to 50% of patients do not respond optimally to disease-modifying therapies (DMTs), and therapeutic response may be influenced by genetic factors such as genetic variants. Therefore, our study aimed to investigate the association of the HLA-DRB1*0403 genetic variant and therapeutic response to DMTs in MS. We included 105 patients with MS diagnosis. No evidence of disease activity based on the absence of clinical relapse, disability progression or radiological activity (NEDA-3) was used to classify the therapeutic response. Patients were classified as follows: (a) controls: patients who achieved NEDA-3; (b) cases: patients who did not achieve NEDA-3. DNA was extracted from peripheral blood leukocytes. HLA-DRB1*0403 genetic variant was analyzed by quantitative polymerase chain reaction (qPCR) using TaqMan probes. NEDA-3 was achieved in 86.7% of MS patients treated with DMTs. Genotype frequencies were GG 50.5%, GA 34.3%, and AA 15.2%. No differences were observed in the genetic variant AA between patients who achieved NEDA-3 versus patients who did not achieve NEDA-3 (48.7% vs. 43.1%, p = 0.6). We concluded that in Mexican patients with MS, HLA-DRB1*0403 was not associated with the therapeutic response to DMTs.

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Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease that affects the nervous system. Peripheral blood leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNA-CN) are potential biomarkers of neurological disability and neural damage. Our objective was to assess the LTL and mtDNA-CN in relapsing-remitting MS (RRMS). We included 10 healthy controls, 75 patients with RRMS, 50 of whom had an Expanded Disability Status Scale (EDSS) from 0 to 3 (mild to moderate disability), and 25 had an EDSS of 3.5 to 7 (severe disability). We use the Real-Time Polymerase Chain Reaction (qPCR) technique to quantify absolute LTL and absolute mtDNA-CN. ANOVA test show differences between healthy control vs. severe disability RRMS and mild-moderate RRMS vs. severe disability RRMS (p = 0.0130). LTL and mtDNA-CN showed a linear correlation in mild-moderate disability RRMS (r = 0.378, p = 0.007). Furthermore, we analyzed LTL between RRMS groups with a ROC curve, and LTL can predict severe disability (AUC = 0.702, p = 0.0018, cut-off < 3.0875 Kb, sensitivity = 75%, specificity = 62%), whereas the prediction is improved with a logistic regression model including LTL plus age (AUC = 0.762, p = 0.0001, sensitivity = 79.17%, specificity = 80%). These results show that LTL is a biomarker of disability in RRMS and is correlated with mtDNA-CN in mild-moderate RRMS patients.

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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.

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BACKGROUND: Between 50-60% of Multiple Sclerosis (MS) patients have cognitive alterations. There are several batteries to assess cognitive impairments in MS, however, few exist for Latin Americans. The objective of this study is to evaluate the neuropsychological profile of Mexican people with MS (PwMS) and assess the utility of Norma Latina, a new battery for cognitive assessment in Latin America, in differentiating cognitive test performance between PwMS and healthy controls (HCs). METHODS: 100 PwMS and 100 HCs from Mexico were evaluated with the Norma Latina battery. The following analyses were conducted: 1) low-percentiles of each participant were calculated, 2) Area Under the Curve was used to determine whether the battery discriminated between PwMS and HCs, 3) four composite scores were calculated, and student's t-test was used to compare groups according to these domains. RESULTS: PwMS obtained a greater number of impaired scores compared to HCs, principally in executive function. The battery successfully discriminated between PwMS and HCs, with the strongest capacity to discriminate in the executive functions, and the weakest in memory. CONCLUSION: Establishing validation of a neuropsychological battery for Mexican PwMS will help to more accurately detect cognitive alterations, which will guide the decisions of professionals in terms of cognitive rehabilitation.

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BACKGROUND: Multiple sclerosis affects more than 2 million people. Clinical decisions are performed under evidence-based medicine. The appearance of new disease-modifying therapies and changes in diagnostic criteria complicates the decision-making process in clinical practice. OBJECTIVES: To characterize the criteria for radiologically isolated syndrome (RIS), clinically isolated syndrome (CIS), and relapsing-remitting multiple sclerosis (RRMS) by Mexican neurologists in a real-world setting. METHODS: A two-round modified Delphi method (RAND/UCLA) was applied. RESULTS: In RIS, LP, spinal cord MRI and VEP should be included in diagnostic testing; DMT initiation is not necessary. A follow-up MRI within 3 months are recommended. In CIS, corticosteroid therapy should be initiated at first relapse; both simple and Gd-enhanced MRI is mandatory. LP, selective blood tests, and NMO-IgG/AQP4 antibodies should be performed as complementary. IFN beta or GA were the most suitable DMTs for treating high-risk CIS. Patients with RRMS should begin with DMT at diagnosis, include a follow-up MRI if a patient had 2 relapses within 6 months. GA and oral DMTs are the most eligible DMTs for mild RRMS. Monoclonal antibodies-based therapy is chosen when disability is present. Radiological criteria for switching DMT included >1 Gd+ lesion and >2 new T2 lesions. CONCLUSIONS: Although many coincidences, there are still many hollows in the medical attention of MS in Mexico. This consensus recommendation could be helpful to implement better evidence-based recommendations and guidelines in a real-world setting.

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INTRODUCTION: Multiple sclerosis is an inflammatory disease, where fibrin deposition and the impairment in its degradation have been shown to play an important role in the demyelination process. Tissue plasminogen activator (tPA) is a serine protease that enhances the conversion of plasminogen into its active form plasmin, the principal tPA inhibitor is the PAI-1. Several PAI-1 polymorphisms impact its gene expression and protein activity. Furthermore, the aim of this study was to investigate the association between the - 844 G>A, HindIII C>G, and 4G/5G PAI-1 polymorphisms and susceptibility to MS. MATERIAL AND METHODS: The study group included 400 Mexican mestizo subjects: 200 unrelated patients and 200 unrelated individuals identified as control subjects. The analysis of PAI-1 polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: A significant association was found between the CG genotype of the HindIII C>G PAI-1 polymorphism and susceptibility to MS (OR = 1.58, p = 0.03); moreover, the frequency of 5G allele and 5G/5G genotype of the 4G/5G PAI-1 polymorphism was statistically significant (OR = 1.36 and p = 0.04 and OR = 2.43 and p = 0.02, respectively). With respect to the relation between the scores of progression (EDSS) and severity (MSSS), no association was found between EDSS and genotypes of the PAI-1 polymorphisms analyzed. Regarding MSSS, male that carries genotype GA of the -844 G>A and genotype 4G/5G of the 4G/5G PAI-1 polymorphisms showed a significant association with an increase of media of MSSS in comparison with females (p = 0.01 in both cases).

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Cognitive impairment affects 40⁻60% of patients with multiple sclerosis. It may be present early in the course of the disease and has an impact on a patient's employability, social interactions, and quality of life. In the last three decades, an increasing interest in diagnosis and management of cognitive impairment has arisen. Neuropsychological assessment and neuroimaging studies focusing on cognitive impairment are now being incorporated as primary outcomes in clinical trials. However, there are still key uncertainties concerning the underlying mechanisms of damage, neural basis, sensitivity and validity of neuropsychological tests, and efficacy of pharmacological and non-pharmacological interventions. The present article aimed to present an overview of the assessment, neural correlates, and impact of cognitive impairment in multiple sclerosis.

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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.

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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.

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Biological drugs and nonbiological complex drugs with expired patents are followed by biosimilars and follow-on drugs that are supposedly similar and comparable with the reference product in terms of quality, safety and efficacy. Unlike simple molecules that can be copied and reproduced, biosimilars and follow-on complex drugs are heterogeneous and need specific regulations from health and pharmacovigilance agencies. A panel of 14 Latin American experts on multiple sclerosis from nine different countries met to discuss the recommendations regarding biosimilars and follow-on complex drugs for treating multiple sclerosis. Specific measures relating to manufacturing, therapeutic equivalence assessment and pharmacovigilance reports need to be implemented before commercialization. Physical, chemical, biological and immunogenic characterizations of the new product need to be available before clinical trials start. The new product must maintain the same immunogenicity as the original. Automatic substitution of biological and complex drugs poses unacceptable risks to the patient.

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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.

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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.

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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.

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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.

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