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Background To date, no studies have used hypnosis to examine and manage the potential emotional causes of multiple sclerosis (MS) in the scientific field; therefore, we decided to compare the effectiveness of hypnoanalysis and guided imagery for determining and manage these emotional causes. Methods Fifteen participants with severe MS were included and assigned into 2 groups: hypnoanalysis and guided imagery. In the hypnoanalysis group, the participants underwent 10 hypnotic sessions to understand events related to the cause of the disease, which were restructured (the events were modified by adding the psychological resources that each involved person needed); in addition, other techniques were used to investigate the causes and solutions according to the participants’ unconscious. The guided imagery group received 10 group sessions of body relaxation and guided imagery, which were recorded for practice at home. Outcome measures, namely, disability (the Expanded Disability Status Scale, EDSS), quality of life (QoL, measured with the SF-36) and number of relapses, were evaluated 4 months previous the intervention, at baseline, post-intervention, and 3 months later. Results Hypnoanalysis revealed that stressful events and psychoemotional maladaptive patterns acted as causal, detonating, or aggravating factors of disease, and psychoemotional changes were the most frequent and varied solutions. No changes were observed in disability between the two groups. The guided imagery group showed an improvement in 2 subscales of QoL when compared with the hypnoanalysis group (which disappeared at the follow-up); this difference is probably due to the increased number of sessions and probably due to psychoemotional maladaptive patterns being more frequently mentioned than difficult circumstances in life and/or unsolved past events. However, the techniques used in hypnoanalysis were effective in understanding the potential emotional causes of MS, which showed high intra- and inter-participant consistency. Conclusions The daily use of guided imagery overcame the restructuring of negative past events to improve QoL in patients with MS. Trial registration ACTRN12618002024224 (retrospectively registered)

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 disability and neurological damage. The present work evaluated LTL and mtDNA-CN in 75 relapsing-remittent MS (RRMS) patients 50 of whom had an Expanded Disability Status Scale (EDSS) 0 to 3 (mild-moderate disability), and 25 had an EDSS of 3.5 to 7 (severe disability). Absolute LTL and absolute mtDNA-CN were measured via real-time polymerase chain reaction (qPCR). The LTL and mtDNA-CN were significantly lower in RRMS severe disability than in RRMS mild-moderate disability (3.924 ± 0.124 vs 2.854 ± 0.092, p

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).

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.

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.

Macrophage migration inhibitory factor (MIF) is a cytokine associated with tissue damage in multiple autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis and psoriatic arthritis. The role of MIF in multiple sclerosis (MS) and the contribution of its polymorphisms are unknown in our population. Therefore, we decided to investigate the genetic association of -794 CATT5-8 (rs5844572) and -173 G>C (rs755622) MIF polymorphisms with MS, clinical variables and MIF serum levels in the population of western Mexico. 230 MS patients diagnosed according to McDonald criteria and 248 control subjects (CS) were recruited for this study, both polymorphisms were genotyped by PCR and PCR-RFLP and MIF serum levels were measured by ELISA kit. Severity and progression of MS were evaluated by EDSS and MSSS scores, respectively. Genotypes carrying the 5 repeats alleles of -794 CATT5-8MIF polymorphism present higher MIF serum levels in comparison with no carriers, and the presence of 5,7 heterozygous genotype contribute to the increase of disease severity and damage progression in MS patients. Notably when we stratified by sex, an effect of risk alleles (7 repeats and -173*C) of both MIF polymorphisms on EDSS and MSSS scores on males was found (p

The percutaneous isolated hepatic perfusion utilizes a venovenous bypass to administer high-dose chemotherapy exclusively in the liver, getting depurated through a hemofilter before returning to the systemic circulation. The hepatic perfusion is managed under general anesthesia and invasive monitoring as a result of very abrupt changes in venous return and vascular resistances because of the isolation of the hepatic territory and absorption of circulating catecholamines by the hemofilter. We report a case in which we describe the technique, physiologic implications, anesthetic, and goal-directed hemodynamic management for this procedure.

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.

Sleep disorders are a widespread condition in patients with Parkinson's disease (PD), which has been linked to a deregulation of the circadian cycle and therefore of the clock genes. The aim of this study was to evaluate the effect of melatonin (MEL) on the PER1 and BMAL1 clock genes in patients with PD. A double-blind, cross-over, placebo-controlled randomized clinical trial pilot study was conducted in 26 patients with stage 1–3 PD according to the Hoehn & Yahr scale, who received either 25 mg of MEL or a placebo at noon and 30 min before bedtime for three months. The relative expression of the PER1 and BMAL1 genes was measured, as well as the presence of daytime, nocturnal, and global sleepiness, and the progression of PD. The levels of the PER1 and BMAL1 genes at baseline were 0.9 (0.1–3) vs. 0.56 (0.1−2.5), respectively; while after the intervention with MEL or placebo the BMAL1 levels increased to 2.5 (0−3.70) vs. 2.2 (0.10–3.30), respectively (d = 0.387). Fifty percent (50 %) of patients had daytime sleepiness and sixty-five percent (65 %) had abnormal nighttime sleepiness, yet neither group showed changes after the intervention. Patients with PD exhibited an alteration in the levels of the clock genes: MEL increased the levels of BMAL1, but the PER1 levels remained unchanged.

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.

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.

Background and objective Women with multiple sclerosis (MS) who intend to get pregnant are often advised to discontinue disease modifying therapy (DMT) prior to conception. This recommendation is not based on medical evidence and may interfere with disease control by immunomodulatory drugs. The present study was designed to help discuss the effect of DMT for MS on pregnancy and on disease course. Patients and methods Retrospective data from 152 pregnancies of 132 women with MS were collected by the physician in charge of the case. All data were entered into a specific file for qualitative and quantitative statistical analysis. Results From the total group of patients, 89 pregnancies occurred without any exposure to MS drugs, while 61 pregnancies occurred with at least eight weeks of exposure to MS immunomodulatory drugs. The rate of obstetric and neonatal complications was similar in both groups, except for the newborn weight and height which was smaller for mothers receiving medications. Mothers’ post-delivery relapse rate and EDSS scores in the follow-up period were significantly higher in the absence of treatment. Conclusion It is possible that, with further such supportive data, international guidelines on MS treatment in young women who intend to get pregnant may need to be revised.

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.

Objetivo: Estima-se que haja aproximadamente 50.000 pessoas com a forma remitente-recorrente da esclerose múltipla na América Latina. Os algoritmos de tratamento norte-americanos e europeus não levam em consideração nossas peculiaridades regionais, nem a dificuldade no acesso ao tratamento por parte dos pacientes. Métodos: O Fórum Latino-americano de Esclerose Múltipla é um grupo de especialistas independente e suprainstitucional, que avaliou as mais recentes evidências científicas sobre a eficácia e a segurança das drogas modificadoras do curso da doença. Foram avaliados também o acesso ao tratamento e os programas de farmacovigilância de cada um dos oito países representados no Fórum. Resultados: Uma lista específica de recomendações baseadas em evidências científicas foi estabelecida para a América Latina. Também foram discutidas perspectivas de futuros tratamentos para esclerose múltipla. Conclusões: O presente estudo representou um esforço dos representantes de oito países latino-americanos em discutir um assunto que não pode ser adaptado para uso em nossa região diretamente a partir de recomendações de tratamento europeias ou norte-americanas. Objective: It is estimated that circa 50,000 individuals have relapsing-remitting multiple sclerosis in Latin America. European and North- American algorithms for the treatment of multiple sclerosis do not foresee our regional difficulties and the access of patients to treatment. Methods: The Latin American Multiple Sclerosis Forum is an independent and supra-institutional group of experts that has assessed the latest scientific evidence regarding efficacy and safety of disease-modifying treatments. Accesses to treatment and pharmacovigilance programs for each of the eight countries represented at the Forum were also analyzed. Results: A specific set of guidelines based upon evidence-based recommendations was designed for Latin America. Future perspectives of multiple sclerosis treatment were also discussed. Conclusions: The present paper translated an effort from representatives of eight countries discussing a matter that cannot be adapted to our region directly from purely European and North-American guidelines for treatment.

Rare autosomal dominant mutations result in familial Alzheimer's disease (FAD) with a relatively consistent age of onset within families. This provides an estimate of years until disease onset (relative age) in mutation carriers. Increased AD risk has been associated with differences in functional magnetic resonance imaging (fMRI) activity during memory tasks, but most of these studies have focused on possession of apolipoprotein E allele 4 (APOE4), a risk factor, but not causative variant, of late-onset AD. Evaluation of fMRI activity in presymptomatic FAD mutation carriers versus noncarriers provides insight into preclinical changes in those who will certainly develop AD in a prescribed period of time. Adults from FAD mutation-carrying families (nine mutation carriers, eight noncarriers) underwent fMRI scanning while performing a memory task. We examined fMRI signal differences between carriers and noncarriers, and how signal related to fMRI task performance within mutation status group, controlling for relative age and education. Mutation noncarriers had greater retrieval period activity than carriers in several AD-relevant regions, including the left hippocampus. Better performing noncarriers showed greater encoding period activity including in the parahippocampal gyrus. Poorer performing carriers showed greater retrieval period signal, including in the frontal and temporal lobes, suggesting underlying pathological processes.

Objective: The prevalence of multiple sclerosis (MS) in Latin America varies across different studies but an intermediate risk and increased frequency of the disease have been reported in recent years. The circumstances of Latin American countries are different from those of Europe and North America, both in terms of differential diagnoses and disease management. Methods: An online survey on MS was sent to 855 neurologists in nine Latin American countries. A panel of nine experts in MS analyzed the results. Results: Diagnostic and therapeutic recommendations were outlined with special emphasis on the specific needs and circumstances of Latin America. The experts proposed guidelines for MS diagnosis, treatment, and follow up, highlighting the importance of considering endemic infectious diseases in the differential diagnoses of MS, the identification of patients at high risk of developing MS in order to maximize therapeutic opportunities, early treatment initiation, and cost-effective control of treatment efficacy, as well as global assessment of disability. Conclusions: The experts recommended that healthcare systems allocate a longer consultation time for patients with MS, which must be conducted by neurologists trained in the management of the disease. All drugs currently approved must be available in all Latin American countries and must be covered by healthcare plans. The expert panel supported the creation of a permanent forum to discuss future clinical and therapeutic recommendations that may be useful in Latin American countries.

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.

Objective: To determine theβ-amyloid precursor protein (βAPP) isoforms ratio as a risk factor for Alzheimer’s Disease and to assess its relationship with demographic and genetic variables of the disease.Methods: Blood samples from 26 patients fulfilling NINCDS-ADRDA diagnostic criteria for AD and 46 healthy control subjects were collected for Western blotting forβAPP. A ratio ofβAPP isoforms, in optical densities, between the upper band (130 Kd) and the lower bands (106–110 Kd) was obtained. Odds ratios were obtained to determine risk factor of this component.Results:βAPP ratio on AD subjects was lower than that of control subjects: 0.3662 ± 0.1891 vs. 0.6769 ± 0.1021 (mean ± SD, pβAPP ratio (βAPP ratio on EOAD subjects of 0.3965 ± 0.1916 was found vs. 0.3445 ± 0.1965 on LOAD subjects (p>0.05).Conclusions: AlteredβAPP isoforms is a high risk factor for Alzheimer’s disease, although it has no influence on the time of onset of the disease.

Objective.—The objective of this study was to document the clinical characteristics of migraine and patterns of medication use in residents ≥15 years old in 12 Latin American urban communities. Background.—Few large-scale population studies have established the symptoms and disability associated with migraine with or without aura in Latin American urban communities or the pattern of medication use in these regions. Methods.—In this study, subjects in 12 urban communities, from 6 Latin American countries, were surveyed with a validated face-to-face interview questionnaire based on International Headache Society criteria for migraine. The questionnaire was completed during face-to-face interviews with headache sufferers within selected households and included questions about migraine symptoms, migraine-related disability, and the use of health-care resources and medications to treat migraines. Results.—Of the 8618 people available for screening, 62% suffered from headaches. Of individuals with migraine, 42% reported consulting a health-care professional about their headaches. Of the migraineurs, 94.2% reported moderate to severe pain. Associated symptoms of nausea or vomiting, photophobia, phonophobia, and osmophobia were common during migraine attacks in 30.3, 76.4, 85.1, and 47.7% of subjects, respectively. The majority of subjects suffered between one and eight migraines each month. Although no previous diagnosis of migraine was reported by 65% of headache sufferers, migraineurs lost an average of 8 days in the preceding 3 months in any of the following areas: school, work, household chores, and/or social, family, or leisure activities. The agents used most widely to treat migraine were paracetamol and salicylates, while nonsteroidal anti-inflammatory drugs, dypirone, and ergotamines were also commonly used. Medication use varied widely among countries, but was predominantly nonprescription. Conclusions.—Migraine is a common disorder in Latin American urban communities imposing significant burden on individuals, families, and communities. The magnitude of the impact and the range of activities affected by migraine are similar to those of previous reports in other regions. The preponderance of nonprescription medications and the scarcity of migraine-specific triptans from the study findings are especially striking.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system associated with demyelination and axonal loss eventually leading to neurodegeneration. MS exhibits many of the hallmarks of an inflammatory autoimmune disorder including breakdown of the blood–brain barrier (BBB). The BBB is a complex organization of cerebral endothelial cells, pericytes and their basal lamina, which are surrounded and supported by astrocytes and perivascular macrophages. In pathological conditions, lymphocytes activated in the periphery infiltrate the central nervous system to trigger a local immune response that ultimately damages myelin and axons. Cytotoxic factors including pro-inflammatory cytokines, proteases, and reactive oxygen and nitrogen species accumulate and may contribute to myelin destruction. Dysregulation of the BBB and transendothelial migration of activated leukocytes are among the earliest cerebrovascular abnormalities seen in MS brains and parallel the release of inflammatory cytokines. In this review we establish the importance of the role of the BBB in MS. Improvements in our understanding of molecular mechanism of BBB functioning in physiological and pathological conditions could lead to improvement in the quality of life of MS patients.

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.

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.

Multiple sclerosis (MS) is a chronic inflammatory disease, which leads to focal plaques of demyelination and tissue injury in the central nervous system. Oxidative stress is also thought to promote tissue damage in multiple sclerosis. Current research findings suggest that omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapenta-enoic acid (EPA) and docosahexaenoic acid (DHA) contained in fish oil may have anti-inflammatory, antioxidant, and neuroprotective effects. The aim of the present work was to evaluate the efficacy of fish oil supplementation on serum proinflammatory cytokine levels, oxidative stress markers, and disease progression in MS. 50 patients with relapsing-remitting MS were enrolled. The experimental group received orally 4 g/day of fish oil for 12 months. The primary outcome was serum TNFαlevels; secondary outcomes were IL-1β1b, IL-6, nitric oxide catabolites, lipoperoxides, progression on the expanded disability status scale (EDSS), and annualized relapses rate (ARR). Fish oil treatment decreased the serum levels of TNFα, IL-1β, IL-6, and nitric oxide metabolites compared with placebo group (P≤0.001). There was no significant difference in serum lipoperoxide levels during the study. No differences in EDSS and ARR were found.Conclusion.Fish oil supplementation is highly effective in reducing the levels of cytokines and nitric oxide catabolites in patients with relapsing-remitting MS.

Alzheimer's disease (AD) is an age-related disorder characterized by deposition of amyloid β-peptide (Aβ) and degeneration of neurons in brain regions such as the hippocampus, re‐ sulting in progressive cognitive dysfunction. The causes of Alzheimer's disease (AD) have not been fully discovered, there are three main hypotheses to explain the phenomenon: a) The deficit of acetylcholine; b) The accumulation of beta-amyloid (Aβ and / or tau protein; and c) Metabolic disorders.

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.

The incidence and prevalence of multiple sclerosis (MS) varies geographically as shown through extensive epidemiological studies performed mainly in developed countries. Nonetheless, scant data is available in Latin America and the Caribbean (LAC). The objective of this review is to assess epidemiological data of MS in LAC. We conducted a systematic review of published articles and gray literature from January 1995 to May 2011. Twenty-two studies met the inclusion criteria after full-text review. Incidence data were found in only three studies and ranged from 0.3 to 1.9 annual cases per 100,000 person-years. Prevalence was reported in 10 studies and ranged from 0.83 to 21.5 cases per 100,000 inhabitants. The most prevalent subtype of MS was the relapsing–remitting form (48% to 91% of the series). No data about mortality were found. This study showed low frequency for MS in LAC compared with North American and European countries. The role of environmental and genetic factors should be well studied, providing new insights about its etiology.

Alzheimer's disease is the most common neurodegenerative disorder worldwide characterized by considerable atrophy and an enlargement and coarsening of the sulci, amyloid formation in neuritic plaques and brain vessels (amyloid angiopathy), neurofibrillary tangles, and neuronal loss, particularly in the limbic and association cortices. In addition, deficits in cholinergic transmission and associated loss of cholinergic cell bodies, granulovacuolar degeneration and rod-shaped eosinophilic inclusions (Hirano bodies) are common in Alzheimer’s disease patients. Clinical symptoms are characterized by progressive worsening of memory, and cognitive impairment accompanied by one of the following symptoms: aphasia, apraxia, agnosia and disorders in the executive function (Selkoe, 2004). The pathophysiological mechanisms that underlie the neurodegenerative characteristic of Alzheimer's disease are yet to be completely understood, although many factors in disease pathogenesis have been identified, and several theories are emerged. In the last years, mitochondrial dysfunction has been considered as a potential factor implicated at some stage of the pathogenic process (Anandatheerthavarada et al., 2003; Sullivan & Brown, 2005

Background and aims . It has been suggested that mitochondrial dysfunction is relevant to Alzheimer disease (AD) and some mitochondrial haplogroups could be related to the risk of AD. Therefore, in this work we have genotyped mtDNA haplogroups in Mexican patients with AD and their respective matched controls. Methods: Haplotyping of 33 AD patients and 49 healthy control subjects was performed using polymerase chain reaction/digest identification of key polymorphic sites in the mitochondrial genome. Results: Mitochondrial haplogroup A is the most frequent in AD patients and controls followed by haplogroup B. The haplogroup C was the least frequent in the control group and it was absent in the AD group. The frequency of haplogroup D was significantly higher in the AD group than in the control group (p = 0.03). Conclusion: There is clear association between the frequency of haplogroup D and Alzheimer disease in the analyzed population from Guadalajara, Mexico. Interestingly the haplogroup C was absent in the AD group. These data requires further study in a larger population to identify these differences more clearly.

regard to APOE-related volumetric changes in mild cognitive impairment (MCI) and normal aging. The MTL is the earliest site of AD pathology, and autopsy studies have demonstrated that MTL pathophysiological changes occur in AD prodromal stages. Thus, we examined for APOE genotypic differences in cortical thickness in normally aging and MCI individuals in the following MTL structures: hippocampus, entorhinal cortex, fusiform gyrus, and parahippocampal gyrus. Methods: Fifty-nine nondemented participants were divided into demographically similar groups based on cognitive status (MCI: n 1⁄4 28; NC: n 1⁄4 29). APOE genotyping was conducted and Freesurfer-derived volumetric and cortical thickness values of MTL structures were compared across groups. Results: Despite no differences in hippocampal volumes or cortical thickness, participants possessing the e4 allele demonstrated significantly decreased thickness of the fusiform gyrus (p 1⁄4 .01), entorhinal cortex (p1⁄4 .002), and parahippocampal gyrus (p1⁄4 .04) relative to those without the e4 allele. Additionally, findings were considerably stronger in the right versus left hemisphere for all significant cortical thickness volumes (all pvalues < .01). Further, APOE-e4 status was predictive of MTL substructure thickness after adjusting for age, stroke risk, and hippocampal volumes. Conclusions: Possession of the APOE-e4 allele was strongly associated with cortical thickness of MTL substructures within our sample of nondemented older adults. Findings were independent of MCI status, hippocampal volumes, and stroke risk, suggesting that, even in the context of normal aging, possession of the APOE-e4 allele is associated with subtle alterations in cortical thickness in MTL structures implicated in the pathogenesis of AD. Interestingly, results revealed hemispheric differences by regional cortical thickness of MTL structures, suggesting a possible right hemisphere predilection for neurobiological changes associated with the APOE-e4 allele.

2 and Lesion Explorer 3 WMH segmentation was performed, with VichowRobin perivascular spaces excluded. To appreciate the 3-dimensional anatomy of WMH, PV-WMH was defined as any hyperintensity touching the ventricles in 3D, the remaining discrete WMSH were defined as DWWMH. Hypointense components within PV-WMH and DW-WMH of cerebrospinal fluid intensity on T1-based segmentation were considered to represent cystic necrosis. Volumetrics were obtained. Hypointense lesion volumes were expressed as percentage of WMH. Results: Mean percentage of hypointensities were as follows: periventricular (AD 2.2%, NC 0.37%); deep white (AD 2.16%, NC 1.6%), with the PV between group difference approaching significance (p .07). Total PV-WMH and DW-WMH volumes was significantly correlated in NC (r .62, p .019) but not in AD (r .32, p .24). However, DW and PV hypointensities did not show correlation (NC: r -.05, p .87; AD: r .24, p .39). Conclusions: The higher percentage of implied cystic necrosis in the PV distribution, and the differences in DW and PV correlations in AD and NC, suggests a different underlying pathology occurring in the periventricular regions of AD patients. It is recommended that future studies examining WMH should include PV and DW delineations as well as an additional T1-based hypointense segmentation to account for these lesions.

Background: Prospective and case-control studies have demonstrated that memory loss and executive dysfunction occur early in Alzheimer disease (AD).Objective: To investigate these observations by the study of persons at risk for autosomal dominant forms of AD.Methods: Neuropsychological and genetic tests were performed on 51 nondemented at-risk members of 10 Mexican families with two distinct presenilin-1 (PS1) mutations. Test scores were compared between PS1 mutation carriers (MCs; n = 30) and noncarriers (NCs; n = 21) by analyses of variance, co-varying for family and specific mutation. Regression analyses were performed, taking into account age relative to the median age at dementia diagnosis in the family (adjusted age), gender, Beck Depression Inventory (BDI) scores, education, and number of APOE ε4 alleles. Subjects were divided into age tertiles and scores compared within these groups. Composite scores for Verbal Memory, Executive Function/Working Memory, Language, and Visuospatial Function were created, and these scores compared between MCs and NCs.Results: MCs performed worse than NCs on the Mini-Mental State Examination, Trails Making Tests A and B, Delayed Recall of a 10-Word List, and Wechsler Adult Intelligence Scale WAIS Block Design. In multiple linear regression analyses, BDI score, gender, and number of APOE ε4 alleles did not consistently affect test scores. The differences seen between MCs and NCs were due to differences in the oldest tertile. MCs had lower Visuospatial and Executive Function/Working Memory but not Verbal Memory or Language composite scores.Conclusions: This study is consistent with findings in sporadic Alzheimer disease of early problems with memory, visuospatial function, and particularly with executive function in PS1 mutation carriers. Depression, gender, and presence of an APOE ε4 allele did not demonstrate large influences on neuropsychological performance.

Although many Alzheimer's disease (AD) patients have a family history of the disease, it is rarely inherited in a predictable way. Functional magnetic resonance imaging (fMRI) studies of nondemented adults carrying familial AD mutations provide an opportunity to prospectively identify brain differences associated with early AD-related changes. We compared fMRI activity of 18 nondemented autosomal dominant AD mutation carriers with fMRI activity in eight of their noncarrier relatives as they performed a novelty encoding task in which they viewed novel and repeated images. Because age of disease onset is relatively consistent within families, we also correlated fMRI activity with subjects' distance from the median age of diagnosis for their family. Mutation carriers did not show significantly different voxelwise fMRI activity from noncarriers as a group. However, as they approached their family age of disease diagnosis, only mutation carriers showed increased fMRI activity in the fusiform and middle temporal gyri. This suggests that during novelty encoding, increased fMRI activity in the temporal lobe may relate to incipient AD processes.

Spanish-language screening tests that are sensitive to the early cognitive changes of Alzheimer's disease (AD) are needed. Persons known to be at 50% risk for young-onset AD due to presenilin-1 (PSEN1) mutations provide the opportunity to assess which measures on the Mini-mental State Examination (MMSE) are most sensitive to these early changes.We performed genetic and Spanish-language cognitive testing on 50 Mexican persons without dementia at risk for inheriting PSEN1 mutations. We then compared the performance on sub-items of the MMSE between PSEN1 mutation carriers (MCs) and non-carriers (NCs) using t-tests and Fisher's exact tests. Exploratory multiple logistic regression analyses were also performed.Twenty-nine persons were MCs and 21 NCs. NCs tended to achieve higher levels of education (p = 0.039) than did MCs. MCs tended to perform more poorly when spelling "MUNDO" backwards and on Orientation, particularly regarding the date. In multiple regression analyses the ability of backwards spelling to predict PSEN1 mutation status was reduced when education was included as an independent variable.Subjects in the earliest stage of PSEN1-related AD showed deficits on orientation to date and in divided attention when spelling backwards. It is unclear if educational level should be considered an associated feature or a con-founding variable in this population although it should be taken into account when considering performance on the MMSE task of divided attention. The relative lack of deficits on delayed recall of three words probably represents the insensitivity of this measure in early AD. This study supports the utility of autosomal dominant AD as a model of the more common sporadic form of the disorder.