Prevalence and clinical features of multiple sclerosis in Latin America

Multiple sclerosis (MS) in Latin America (LA) is considered to have a low to medium prevalence. However, accurate information on MS in LA is scarce. The aim of this study was to compare clinical characteristics among LA patients through a systematic review of the literature. A systematic search (Spanish, Portuguese and English) was done for all clinical studies of MS in humans (MEDLINE, PubMed, Scielo, BIREME, EMBASE and LILACS) up to May 2011 being focused on a well-defined Latin American population (peer-reviewed journal) following the MOOSE guidelines. The search strategy included combinations of different Mesh terms (two independent researchers). Classification of each article by using the Oxford Centre for Evidence-based Medicine – Levels of Evidence was done. The total number of patients per country for each specific characteristic was compiled. Chi-square test was used to compare the characteristics in the studies retrieved per country. There were 38 articles fulfilling the inclusion criteria, accounting for 4524 patients. Relapsing-remitting form was the most frequent in LA patients and the main initial symptom was motor, followed by optic neuritis and sensorial. A mild expanded disability status scale was the most prevalent in all LA countries. Factors accounting for differences in distribution and clinical course across LA countries include genetics, environment, diagnostic techniques, socioeconomic structure and medical facilities.     

MS in Latin America

During the last few years, there has been an increasing desire to study and expand current knowledge about the different aspects of Multiple Sclerosis (MS) in Latin America (LATAM). This report analyzes epidemiological data and specific aspects of MS in this region and aims to describe the current situation, based on the very few scientific publications that contain reliable information. Everything seems to indicate that MS in LATAM has some special characteristics that makes it different from what has been described in other areas of the world. Nevertheless, more thorough research has to be carried out in order to obtain conclusive data regarding the behaviour of the disease in LATAM.     

Influenza vaccination status in multiple sclerosis patients from Latin America

Journal of NeuroVirology - The objective of the present study was to identify the frequency of MS patients in Latin America (LATAM) that received the influenza vaccine during the most recent season...     

The prevalence of multiple sclerosis in the world: an update

The systematic study of multiple sclerosis (MS) in populations, started in 1929 by Sydney Allison, now consists of over 400 publications dealing with the prevalence of MS throughout the world. However, any attempt to redefine the pattern of geographical differences in MS frequency remains as difficult as ever. The comparison of prevalence studies carried out in different areas and times is made difficult by the variability in surveyed population sizes, age structures, ethnic origins and composition, and the difficult quantification of numerators, especially regarding the recognition of benign and very early cases. Additionally, complete case ascertainment depends on access to medical care, local medical expertise, number of neurologists, accessibility and availability of new diagnostic procedures, the degree of public awareness about MS, and the investigators' zeal and resources. Critical examination of the more recent data on MS prevalence leads to some revisions of previously held concepts, the most interesting of which is the appreciation of the greater influence of genetic factors on disease acquisition. The rarity of MS among Samis, Turkmen, Uzbeks, Kazakhs, Kyrgyzis, native Siberians, North and South Amerindians, Chinese, Japanese, African blacks and New Zealand Maoris, as well as the high risk among Sardinians, Parsis and Palestinians, clearly indicate that the different susceptibilities of distinct racial and ethnic groups are an important determinant of the uneven geographic distribution of the disease. The updated distribution of MS in Europe, showing many exceptions to the previously described north-south gradient, requires more explanation than simply a prevalence-latitude relationship. Prevalence data imply that racial and ethnic differences are important in influencing the worldwide distribution of MS and that its geography must be interpreted in terms of the probable discontinuous distribution of genetic susceptibility alleles, which can however be modified by environment. Because the environmental and genetic determinants of geographic gradients are by no means mutually exclusive, the race versus place controversy is, to some extent, a useless and sterile debate.     

Western and Asian features of multiple sclerosis in Mexican Mestizos

OBJECTIVES: The objective of this study was to compare the clinical expression of MS in Mexican Mestizos with that of patients of European or Asian descent; as well as to compare the annual frequency of new cases with that observed in the previous decades. PATIENTS AND METHODS: All patients with diagnosis of definite MS seen at the National Institute of Neurology and Neurosurgery of Mexico from January 1993 to December 2003 were studied (n=312). Sociodemographic and clinical characteristics were compared with reports of patients from either Western or Asian origin; the long-term disability score was analyzed according to gender, age of onset of MS and the initial symptom. RESULTS: The clinical expression of MS in Mexican Mestizos shares some characteristics with both, Asian and Western forms of MS indicating that the genetic composition of Mexican Mestizos participates in the clinical expression of the disease. Also, at the prevalence date, the mean age of patients and the duration of the disease were lower in our patients than in MS patients from endemic countries suggesting a true increasing incidence in recent times, rather than only improved case ascertainment. CONCLUSIONS: Clinical expression of MS in Mexican Mestizos shows the coexistence of some features common in European and in Asian cases.     

Exploratory analysis of the genetics of impulse control disorders in Parkinson's disease using genetic risk scores

ObjectiveTo study the association between impulse control disorders (ICDs) in Parkinson's disease (PD) and genetic risk scores (GRS) for 40 known or putative risk factors (e.g. depression, personality traits).BackgroundIn absence of published genome-wide association studies (GWAS), little is known about the genetics of ICDs in PD. GRS of related phenotypes, for which large GWAS are available, may help shed light on the genetic contributors of ICDs in PD.MethodsWe searched for GWAS on European ancestry populations with summary statistics publicly available for a broad range of phenotypes, including other psychiatric disorders, personality traits, and simple phenotypes. We separately tested their predictive ability in two of the largest PD cohorts with clinical and genetic available: the Parkinson's Progression Markers Initiative database (N = 368, 33% female, age range = [33–84]) and the Drug Interaction With Genes in Parkinson's Disease study (N = 373, 40% female, age range = [29–85]).ResultsWe considered 40 known or putative risk factors for ICDs in PD for which large GWAS had been published. After Bonferroni correction for multiple comparisons, no GRS or the combination of the 40 GRS were significantly associated with ICDs from the analyses in each cohort separately and from the meta-analysis.ConclusionAlbeit unsuccessful, our approach will gain power in the coming years with increasing availability of genotypes in clinical cohorts of PD, but also from future increase in GWAS sample sizes of the phenotypes we considered. Our approach may be applied to other complex disorders, for which GWAS are not available or limited.     

Epidemiology of multiple sclerosis in U.S. veterans: V. Ancestry and the risk of multiple sclerosis

Self-reported ancestry data for the U.S. population from the 1980 decennial census and multiple sclerosis (MS) risk data derived from a large series of World War II white male veterans with MS and matched controls were aggregated on a state level and analyzed to determine the relationship between ancestry and MS risk. A significant portion of the state-by-state variation in MS risk is explainable statistically by differences in ancestry among state populations, even when geographic latitude is included in analyses. In the main, Swedish and other Scandinavian ancesty is most consistently associated with places with increased MS risk. In some analyses, Italian, French, and (to a lesser extent) Scottish ancestries are also associated with increased risk, whereas English and Dutch ancestries are each associated with decreased risk, but most of these non-Scandinavian correlations may effect predomininatly geography per se. These findings provide evidence that ancestry of the resident population, a confounded measure of genetic susceptibility and cultural evironment, is part of the complicated picture of MS as a disease of place.     

Nursing home residents with multiple sclerosis: comparisons of African American residents to white residents at admission

This research profiles African American residents with multiple sclerosis (MS) at admission to the nursing facility and compares them to profiles of white residents with MS using the Minimum Data Set (MDS). We analysed MDS admission assessments for 1367 African Americans with MS and 9294 whites with MS. African American residents with MS were significantly younger at admission than white residents with MS, with almost one half of these African Americans 50 years or younger compared to only one quarter of these whites. African American residents with MS were significantly more physically disabled and cognitively impaired at admission than white residents with MS. Although there were significant racial differences in disability, there were no significant racial differences among these MS residents in the use of various therapies provided by qualified therapists. These observed racial differences among MS residents in disease manifestations, severity, progression and disability are due to multiple variables and point out the need for more research. By combining discoveries from genetics, immunology, epidemiology and virology we can gain a better understanding of the complex pathophysiology of MS and develop more effective treatments and preventive measures. Our findings also indicate potential racial disparities in the use of MS-related care, illustrating that a greater outreach effort may be needed to evaluate and treat African Americans with MS.     

Genome‐wide association studies of bipolar disorder: A systematic review of recent findings and their clinical implications

Recent advances in molecular genetics have enabled assessments of the associations among genetic variants (e.g., single‐nucleotide polymorphisms) and susceptibility for complex diseases, including psychiatric disorders. Specifically, genome‐wide association studies (GWAS), meta‐analyses of the GWAS summary statistics, and mega‐analyses (which use raw data, not summary statistics) of GWAS have provided revolutionary results and have identified numerous susceptibility genes or single‐nucleotide polymorphisms. By using several tens of thousands of subjects, >40 genes have been identified as being associated with susceptibility for bipolar disorder so far. The purpose of this systematic review was to summarize the recent findings of bipolar disorder GWAS and discuss their clinical implications.     

The three new pathways leading to Alzheimer's disease

Genome-wide association studies (GWAS) promise a significant impact on the understanding of late-onset Alzheimer's disease (LOAD) as the genetic components have been estimated to account for 60-80% of the disease. The recent publication of results from large GWAS suggests that LOAD is now one of the best-understood complex disorders. Four recent large LOAD GWAS have resulted in the identification of nine novel loci. These genes are CLU--clusterin, PICALM--phosphatidylinositol-binding clathrin assembly protein, CR1--complement receptor 1, BIN1--bridging integrator 1, ABCA7--ATP-binding cassette transporter, MS4A cluster--membrane-spanning 4-domains subfamily A, CD2AP--CD2-associated protein, CD33--sialic acid-binding immunoglobulin-like lectin and EPHA1--ephrin receptor A1. Collectively, these genes now explain around 50% of LOAD genetics and map on to three new pathways linked to immune system function, cholesterol metabolism and synaptic cell membrane processes. These three new pathways are not strongly linked to the amyloid hypothesis that has driven so much recent thinking and open up avenues for intensive research with regard to the potential for therapeutic intervention.     

Multiple sclerosis in G: genes and geography

Multiple sclerosis (MS) shows uneven geographic distribution globally as well as within countries. In epidemiological studies we have previously demonstrated that there is a high-risk focus for MS in the southern Ostrobothnian region of western Finland. In genetic studies we recently identified haplotypes that associate with MS specifically in patients originating from southern Ostrobothnia suggesting a founder effect. Such haplotypes can be used as molecular tools for tracing common ancestry between patients in different geographic locations. In addition to providing clues to the historical origin, such a genetic archeological approach should help narrow the size of the shared haplotype, thus facilitating the identification of etiological variants and possibly define a superfamily of MS patients with common pathogenetic mechanisms.     

Genetisches Profil der Multiplen Sklerose: Risikogene und die ?dunkle Materie“

Multiple sclerosis (MS) is a genetically complex disease caused by the interplay of genetic and environmental factors. While it shows substantial familial accumulation, there is no evidence for typical Mendelian transmission within families. Instead, MS risk is likely governed by dozens to hundreds of genetic variants, which can also be present in the general population. The strongest genetic risk factor for MS was identified 40 years ago and lies within the HLA locus. It increases the risk of developing MS by two- to threefold. Within the last few years, genome-wide association studies (GWAS) have led to the identification of nearly 60 additional genetic risk loci. Each of these loci yields a modest to moderate risk increase (odds ratios of 1.1-1.3). Even in combination, however, the currently known risk variants merely account for a small fraction of the disease's heritability. It is likely that a major fraction of genetic MS risk that cannot be explained by GWAS, sometimes termed the "dark matter" of GWAS, is caused by other factors, such as structural variations of the genome, rare sequence variants, or inherited epigenetic modifications.     

Epigenetic Modifications and Therapy in Multiple Sclerosis

Breakthroughs in genetic studies, like whole human genome sequencing and genome-wide association studies (GWAS), have richened our knowledge of etiopathology of autoimmune diseases (AID) through discovery of genetic patterns. Nonetheless, the precise etiology of autoimmune diseases remains largely unknown. The lack of complete concordance of autoimmune disease in identical twins suggests that non-genetic factors also play a major role in determining disease susceptibility. Although there is no certain definition, epigenetics has been known as heritable alterations in gene function without changes in the nucleotide sequence. DNA methylation, histone modifications, and microRNA-associated gene expression suppression are the central mechanisms for epigenetic regulations. Multiple sclerosis (MS) is a disorder of the central nervous system (CNS), characterized by both inflammatory and neurodegenerative features. Although studies on epigenetic alterations in MS only began in the past decade, a mounting number of surveys suggest that epigenetic changes may be involved in the initiation and development of MS, probably through bridging the effects of environmental risk factors to genetics. Arming with clear understanding of epigenetic dysregulations underpins development of epigenetic therapies. Identifying agents inhibiting the enzymes controlling epigenetic modifications, particularly DNA methyltransferases and histone deacetylases, will be promising therapeutic tool toward MS. In the article underway, it is aimed to go through the recent progresses, attempting to disclose how epigenetics associates with the pathogenesis of MS and how can be used as therapeutic approach.     

Ethnic heterogeneity of the factor XIII Val34Leu polymorphism

A polymorphism in the coagulation factor XIII gene (FXIII Val34Leu) has been recently described to confer protection for arterial and venous thrombosis and to predispose to intracerebral hemorrhage. At present it is known that FXIII Val34Leu is prevalent in Caucasians, but information upon its distribution in different ethnic groups is scarce. We investigated the prevalence of FXIIIVal34Leu in 450 unrelated subjects of four ethnic groups: 97 Caucasians (Brazilians of European descent and Portuguese), 149 Blacks (Brazilians, and Africans from Cameroon, Zaire and Angola), 40 Asians (Japanese descendents) and 164 Amerindians from South America. PCR amplification of exon 2 of FXIII gene followed by MseI restriction-digestion was employed to define the genotypes. FXIIIVal34Leu was detected in 44.3% of the Caucasians, in 28.9% of the Blacks, in 2.5% of the Asians and in 51.2% of the Amerindians. These data confirm that FXIII Val34Leu is highly prevalent in Caucasians and indicate that it is rarer in populations of African origin. The very high frequency among Amerindians indicates that FXIII Val34Leu is not absent among Asians, and since it has a very low prevalence in Japanese, a heterogeneity in its distribution in Asia may be inferred. Taken together, our data showed that FXIII Val34Leu exhibits a significant ethnic heterogeneity, a finding that is relevant for studies relating this polymorphism with thrombotic and bleeding disorders.     

Insights into the genetics of gastroesophageal reflux disease (GERD) and GERD‐related disorders

Gastroesophageal reflux disease (GERD) is associated with obesity and hiatal hernia, and often precedes the development of Barrett's esophagus (BE) and esophageal adenocarcinoma (EA). Epidemiological studies show that the global prevalence of GERD is increasing. GERD is a multifactorial disease with a complex genetic architecture. Genome‐wide association studies (GWAS) have provided initial insights into the genetic background of GERD. The present review summarizes current knowledge of the genetics of GERD and a possible genetic overlap between GERD and BE and EA. The review discusses genes and cellular pathways that have been implicated through GWAS, and provides an outlook on how future molecular research will enhance understanding of GERD pathophysiology.     

Parental bonding and anxiety: Differences between African American and European American college students

Empirical evidence suggests that early home environments characterized by low care and high overprotection are positively associated with the adult expression of anxiety. While available evidence supports this position for European Americans, there has been no examination of the relationship between perceived parental rearing practices and anxiety among African Americans despite the theoretical assertion that African American parenting environments may be characterized as somewhat more overprotective than European Americans. This study investigated the relationship between maternal rearing patterns and trait and state measures of anxiety and depression among a sample of 59 African American and 55 European American college students. Results indicated that both groups reported similar levels of anxiety, depression, perceived care, and perceived overprotection. European Americans exhibited the typical pattern of a negative relationship between anxiety, depression, and care and a positive relationship between anxiety and overprotection. African Americans evidenced a similar negative relationship between anxiety, depression, and care, but no relationship between anxiety, depression, and overprotection. Furthermore, specific aspects of ethnic identity (i.e., ethnic achievement, ethnic behaviors) were found to be negatively associated with measures of trait anxiety among African Americans but not European Americans.     

Alzheimer's disease, genes, and environment: the value of international studies.

OBJECTIVE: To describe the construction of a disease model incorporating both genetic an environmental factors in the etiology of Alzheimer's disease (AD), using data generated from the Indianapolis-Ibadan dementia project (I-IDP). METHOD: The I-IDP is a longitudinal comparative study of the prevalence and incidence o dementia in 2 communities: elderly African Americans living in Indianapolis, Indiana, an Yoruba living in Ibadan, Nigeria. RESULTS: African Americans are more than twice as likely as Yoruba to develop AD. Possible explanations for this finding include genetic factors: the possession of the apolipoprotein E epsilon4 allele does not increase risk for AD among Yoruba but confers a sligh increase in AD risk for African Americans. As well, environmental factors may play a role: African Americans have a higher risk of vascular risk factors than do Yoruba. CONCLUSIONS: International comparative studies, particularly those involving population from developing and developed countries, offer a unique opportunity for applying new in formation regarding population genetics to traditional AD risk factor research.     

Characteristics and comorbidity of ADHD sib pairs in the Central Valley of Costa Rica

BackgroundWhile genetic epidemiological studies demonstrate a substantial degree of genetic predisposition for attention-deficit/hyperactivity disorder (ADHD), they also suggest that the genetics are complex and may differ between populations or ethnic groups.ObjectiveThis study describes the phenomenology of siblings with ADHD from the genetically isolated population of the Central Valley of Costa Rica.MethodsRates of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)–defined ADHD subtypes and comorbid conditions were calculated in a sample of 157 ADHD-affected children (probands and siblings) recruited for genetic studies using standardized approaches. Sib-sib comparisons and logistic regressions were conducted to identify significant patterns of concordance.ResultsCombined-type ADHD (69.5%) was the most common subtype among probands, followed by the inattentive (27.4%), and hyperactive-impulsive (3.2%) subtypes. Anxiety disorders were prevalent (55.9%), as were disruptive behavior disorders (30.9%) and Tourette disorder (17.0%). Probands and siblings showed high sib-sib concordance for anxiety disorders.ConclusionsADHD in Costa Rica is similar in clinical and demographic characteristics to ADHD seen in other parts of the world, although the rates of co-occurring psychiatric disorders differ somewhat from those previously reported in Latin American samples. Comorbid anxiety is prevalent, with high rates of sib-sib concordance, and may represent a distinct, homogeneous subgroup suitable for genetic studies.     

Association between genetic variation in a region on chromosome 11 and schizophrenia in large samples from Europe

Recent molecular studies have implicated common alleles of small to moderate effect and rare alleles with larger effect sizes in the genetic architecture of schizophrenia (SCZ). It is expected that the reliable detection of risk variants with very small effect sizes can only be achieved through the recruitment of very large samples of patients and controls (that is tens of thousands), or large, potentially more homogeneous samples that have been recruited from confined geographical areas using identical diagnostic criteria. Applying the latter strategy, we performed a genome-wide association study (GWAS) of 1169 clinically well characterized and ethnically homogeneous SCZ patients from a confined area of Western Europe (464 from Germany, 705 from The Netherlands) and 3714 ethnically matched controls (1272 and 2442, respectively). In a subsequent follow-up study of our top GWAS results, we included an additional 2569 SCZ patients and 4088 controls (from Germany, The Netherlands and Denmark). Genetic variation in a region on chromosome 11 that contains the candidate genes AMBRA1, DGKZ, CHRM4 and MDK was significantly associated with SCZ in the combined sample (n=11?540; P=3.89 × 10(-9), odds ratio (OR)=1.25). This finding was replicated in 23?206 independent samples of European ancestry (P=0.0029, OR=1.11). In a subsequent imaging genetics study, healthy carriers of the risk allele exhibited altered activation in the cingulate cortex during a cognitive control task. The area of interest is a critical interface between emotion regulation and cognition that is structurally and functionally abnormal in SCZ and bipolar disorder.