Modification of post-traumatic epilepsy by fecal microbiota transfer.

It has been well established that traumatic brain injury (TBI) modifies the composition of gut microbiome. Epilepsy, which represents one of the common sequelae of TBI, has been associated with dysbiosis. Earlier study showed that the risk of post-traumatic epilepsy (PTE) after lateral fluid percussion injury (LFPI) in rats can be stratified based on pre-existing (i.e., pre-TBI) gut microbiome profile. In the present study, we examined whether fecal microbiota transfer (FMT) from naïve rats with different prospective histories of PTE would affect the trajectory of PTE in recipients. Fecal samples were collected from naïve adult male Sprague-Dawley rats, followed by LFPI. Seven months later, upon four weeks of vide-EEG monitoring (vEEG), the rats were categorized as those with and without PTE. Recipients were subjected to LFPI, followed by FMT from donors with and without impending PTE. Control groups included auto-FMT and no-FMT subjects. Seven month after LFPI, recipients underwent four-week vEEG to detect spontaneous seizures. After completing vEEG, rats of all groups underwent kindling of basolateral amygdala. Fecal microbiota transfer from donors with impending PTE exerted mild-to-moderate pro-epileptic effects in recipients, evident as marginal increase in multiple spontaneous seizure incidence, and facilitation of kindling. Analysis of fecal samples in selected recipients and their respective donors confirmed that FMT modified microbiota in recipients along the donors' lines, albeit without full microbiome conversion. The findings provide further evidence that gut microbiome may actively modulate the susceptibility to epilepsy.

Fungal and Bacterial Microbiome in Sinus Mucosa of Patients with and without Chronic Rhinosinusitis.

OBJECTIVES: Dysbiosis of the sinonasal microbiome has been implicated in the pathogenesis of chronic rhinosinusitis (CRS). However, the mycobiome remains largely understudied, and microbial alterations associated with specific CRS subtypes have yet to be delineated. The objective of this study is to investigate the fungal and bacterial microbiome of sinus mucosa in CRS patients with and without nasal polyposis (CRSwNP and CRSsNP) versus healthy controls. METHODS: Sinus mucosa was obtained from 92 patients (31 CRSsNP, 31 CRSwNP, and 30 controls) undergoing endoscopic sinus/skull base surgery. Data regarding demographics, Lund-MacKay scores, and histopathology were collected. Fungal and bacterial microbiome analysis was performed utilizing internal transcribed spacer amplicon and 16S rRNA sequencing. RESULTS: Beta diversity of the sinonasal mycobiome differed significantly between CRS and controls (p = 0.001) and between CRSwNP and controls (p = 0.049), but not between CRSwNP and CRSsNP (p = 0.32) nor between CRSsNP and controls (p = 0.06). With respect to the bacterial microbiome, significantly lower alpha diversity was observed between CRS and controls (p < 0.001), CRSwNP versus controls (p < 0.001), and CRSsNP versus controls (p < 0.001). Beta diversity was also significantly different at the genus level between CRSwNP and CRSsNP (p = 0.019), CRSwNP and controls (p = 0.002)), and CRSsNP and controls (p < 0.001). However, alpha and beta diversity did not differ significantly between CRS patients with/without eosinophils or correlate with Lund-MacKay scores. CONCLUSIONS: Differences in mycobiota diversity in CRS patients in comparison with controls suggest that alterations in the mycobiome may contribute to disease pathogenesis. Our findings also confirmed that diminished diversity among bacterial communities is associated with CRS and that significant differences are present in microbial composition between CRSwNP and CRSsNP. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:1054-1062, 2024.

[Core data set for real world data in multiple sclerosis: customization for latin america from a global task force recommendation]. / Core data set para la generación de datos de la vida real en esclerosis múltiple: adaptación de una iniciativa global para América Latina.

INTRODUCTION: The primary objective of the core data set is to reduce heterogeneity and promote harmonization among data sources in EM, thereby reducing the time needed to execute real life data collection efforts. Recently, a group led by the Multiple Sclerosis Data Alliance has developed a core data set for collecting real-world data on multiple sclerosis (MS) globally. Our objective was to adapt this global data set to the needs of Latin America, so that it can be implemented by the registries already developed and in the process of development in the region. MATERIAL AND METHODS: A working group was formed regionally, the core data set created globally was adapted (translation process into Spanish, incorporation of regional variables and consensus on variables to be used). Consensus was obtained through the remote Delphi methodology of a round of questionnaires and remote discussion of the core data set variables. RESULTS: A total of 25 professionals from Latin America carried out the adaptation process between November 2022 and July 2023. Agreement was established on a core data set of nine categories and 45 variables, version 2023 to suggest its implementation in developed or developing registries, and MS cohorts in the region. CONCLUSION: The core data set seeks to harmonize the variables collected by registries and cohorts in MS in Latin America in order to facilitate said collection and allow collaboration between sources. Its implementation will facilitate real life data collection and collaboration in the region.

TITLE: Core data set para la generación de datos de la vida real en esclerosis múltiple: adaptación de una iniciativa global para América Latina.Introducción. Los objetivos primarios del core data set son reducir la heterogeneidad y promover la armonización entre las fuentes de datos en la esclerosis múltiple (EM), reduciendo así el tiempo necesario para ejecutar esfuerzos en la recolección de datos de vida real. Recientemente, un grupo liderado por la Multiple Sclerosis Data Alliance ha desarrollado un core data set para la recolección de datos del mundo real en EM a nivel global. Nuestro objetivo ha sido adaptar y consensuar este conjunto de datos globales a las necesidades de América Latina para que pueda ser implementado por los registros ya desarrollados y en proceso de desarrollo en la región. Material y métodos. Se conformó un grupo de trabajo regionalmente y se adaptó el core data set creado globalmente (proceso de traducción al español, incorporación de variables regionales y consenso sobre variables que se iban a utilizar). El consenso se obtuvo a través de la metodología Delphi remoto de ronda de cuestionarios y discusión a distancia de las variables del core data set. Resultados. Veinticinco profesionales de América Latina llevaron adelante el proceso de adaptación entre noviembre de 2022 y julio de 2023. Se estableció un acuerdo sobre un core data set de nueve categorías y 45 variables, versión 2023, con la sugerencia de implementarlo en registros desarrollados o en vías de desarrollo y cohortes de EM en la región. Conclusión. El core data set busca armonizar las variables recolectadas por los registros y las cohortes de EM en América Latina con el fin de facilitar dicha recolección y permitir una colaboración entre fuentes. Su implementación facilitará la recolección de datos de vida real y la colaboración en la región.

Development of the oral resistome during the first decade of life.

Antibiotic overuse has promoted the spread of antimicrobial resistance (AMR) with significant health and economic consequences. Genome sequencing reveals the widespread presence of antimicrobial resistance genes (ARGs) in diverse microbial environments. Hence, surveillance of resistance reservoirs, like the rarely explored oral microbiome, is necessary to combat AMR. Here, we characterise the development of the paediatric oral resistome and investigate its role in dental caries in 221 twin children (124 females and 97 males) sampled at three time points over the first decade of life. From 530 oral metagenomes, we identify 309 ARGs, which significantly cluster by age, with host genetic effects detected from infancy onwards. Our results suggest potential mobilisation of ARGs increases with age as the AMR associated mobile genetic element, Tn916 transposase was co-located with more species and ARGs in older children. We find a depletion of ARGs and species in dental caries compared to health. This trend reverses in restored teeth. Here we show the paediatric oral resistome is an inherent and dynamic component of the oral microbiome, with a potential role in transmission of AMR and dysbiosis.

The gut microbiota in anxiety and depression - A systematic review.

Growing evidence indicates the community of microorganisms throughout the gastrointestinal tract, (i.e., gut microbiota), is associated with anxiety and depressive disorders. We present the first systematic review of the gut microbiota in anxiety disorders, along with an update in depression. Consideration of shared underlying features is essential due to the high rates of comorbidity. Systematic searches, following PRISMA guidelines, identified 26 studies (two case-control comparisons of the gut microbiota in generalised anxiety disorder, 18 in depression, one incorporating both anxiety/depression, and five including symptom-only measures). Alpha and beta diversity findings were inconsistent; however, differences in bacterial taxa indicated disorders may be characterised by a higher abundance of proinflammatory species (e.g., Enterobacteriaceae and Desulfovibrio), and lower short-chain fatty acid producing-bacteria (e.g., Faecalibacterium). Several taxa, and their mechanisms of action, may relate to anxiety and depression pathophysiology via communication of peripheral inflammation to the brain. Although the gut microbiota remains a promising target for prevention and therapy, future research should assess confounders, particularly diet and psychotropic medications, and should examine microorganism function.

Bugs and Brains, the Gut and Mental Health Study: a mixed-methods study investigating microbiota composition and function in anxiety, depression and irritable bowel syndrome.

INTRODUCTION: Research has highlighted relationships between the micro-organisms that inhabit our gastrointestinal tract (oral and gut microbiota) with host mood and gastrointestinal functioning. Mental health disorders and functional gastrointestinal disorders co-occur at high rates, although the mechanisms underlying these associations remain unclear. The Bugs and Brains Study aims to investigate complex relationships between anxiety/depression and irritable bowel syndrome (IBS) in two ways. First, its primary component will compare the gut and oral microbiota in females with anxiety/depression and/or IBS relative to controls, and investigate underlying physiological, endocrine and immune factors, as well as associations with diet and psychosocial factors. In an ancillary component, the study will also investigate gastrointestinal and mental health symptoms in a larger sample, and explore relationships with diet, exercise, oral health, substance use, medical history, early life adversity and psychosocial factors. METHODS AND ANALYSIS: The Bugs and Brains Study aims to recruit 160 females to the primary component: (1) 40 controls; (2) 40 participants with a depressive/anxiety disorder, but no IBS; (3) 40 participants with IBS, but no depressive/anxiety disorder and (4) 40 participants with both depressive/anxiety disorder and IBS. Participation is completed within 1 month, and involves comprehensive questionnaires, anthropometrics, a diagnostic clinical interview, collection of two saliva samples, and stool, urine and hair samples. This study aims to use a systems biology approach to characterise oral and gut microbial composition and function using 16S rRNA gene sequencing and nuclear MR spectroscopy. As part of the ancillary component, it will collect questionnaire data from 1000 participants aged 18-40 years, capturing mental health, gastrointestinal health, oral health, diet and psychosocial factors. ETHICS AND DISSEMINATION: Approval was granted by the University of Melbourne Human Research Ethics Committee (#1749221). All participants voluntarily provided informed consent. Results will be published in peer-reviewed journals and presented at scientific conferences.

[Argentinean consensus guidelines on the identification and clinical care of secondary progressive multiple sclerosis]. / Consenso sobre la identificación y seguimiento de la esclerosis múltiple secundaria progresiva en Argentina.

INTRODUCTION: The identification, diagnosis, follow-up, and treatment of patients with secondary progressive multiple sclerosis (SPMS) show significant differences between health care professionals in Argentina. AIM: To provide consensus recommendations on the management of patients with SPMS in Argentina to optimize patient care. DEVELOPMENT: A panel of expert neurologists from Argentina dedicated to the diagnosis and care of multiple sclerosis patients gathered during 2019 and 2020 to carry out a consensus recommendation on the diagnosis and treatment of SPMS patients in Argentina. To achieve consensus, the methodology of 'formal consensus-RAND/UCLA method' was used. Recommendations were established based on published evidence and the expert opinion. Recommendations focused on how to define SPMS and how to follow SPMS patients. CONCLUSION: The recommendations of this consensus guidelines attempt to optimize the care of SPMS patients in Argentina.

TITLE: Consenso sobre la identificación y seguimiento de la esclerosis múltiple secundaria progresiva en Argentina.Introducción. Existen diferencias significativas en el diagnóstico, la identificación y el seguimiento de pacientes con esclerosis múltiple secundaria progresiva (EMSP) entre los profesionales de la salud a cargo de su tratamiento. Objetivo. Proveer recomendaciones sobre el tratamiento de los pacientes con EMSP en Argentina con el fin de optimizar su cuidado. Desarrollo. Un grupo de neurólogos expertos en esclerosis múltiple de Argentina elaboró un consenso para el tratamiento de pacientes con EMSP en la región mediante metodología de ronda de encuestas a distancia y reuniones presenciales. Se establecieron 33 recomendaciones basadas en la evidencia publicada y en el criterio de los expertos que participaron. Las recomendaciones se enfocaron en el diagnóstico y el seguimiento de los pacientes con EMSP. Conclusión. Las recomendaciones establecidas en el presente consenso permitirían optimizar el cuidado y el seguimiento de los pacientes con EMSP en Argentina.

Effect of glatiramer acetate on conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Glatiramer acetate, approved for the treatment of relapsing-remitting multiple sclerosis, reduces relapses and disease activity and burden monitored by MRI. We assessed the efficacy of early treatment with glatiramer acetate in delaying onset of clinically definite multiple sclerosis. METHODS: In this randomised, double-blind trial, undertaken in 80 sites in 16 countries, 481 patients presenting with a clinically isolated syndrome with unifocal manifestation, and two or more T2-weighted brain lesions measuring 6 mm or more, were randomly assigned to receive either subcutaneous glatiramer acetate 20 mg per day (n=243) or placebo (n=238) for up to 36 months, unless they converted to clinically definite multiple sclerosis. The randomisation scheme used SAS-based blocks stratified by centre, and patients and all personnel were masked to treatment assignment. The primary endpoint was time to clinically definite multiple sclerosis, based on a second clinical attack. Analysis was by intention to treat. A preplanned interim analysis was done for data accumulated from 81% of the 3-year study exposure. This study was registered with ClinicalTrials.gov, number NCT00666224. FINDINGS: All randomly assigned participants were analysed for the primary outcome. Glatiramer acetate reduced the risk of developing clinically definite multiple sclerosis by 45% compared with placebo (hazard ratio 0.55, 95% CI 0.40-0.77; p=0.0005). The time for 25% of patients to convert to clinically definite disease was prolonged by 115%, from 336 days for placebo to 722 days for glatiramer acetate. The most common adverse events in the glatiramer acetate group were injection-site reactions (135 [56%] glatiramer acetate vs 56 [24%] placebo) and immediate post-injection reactions (47 [19%] vs 12 [5%]). INTERPRETATION: Early treatment with glatiramer acetate is efficacious in delaying conversion to clinically definite multiple sclerosis in patients presenting with clinically isolated syndrome and brain lesions detected by MRI. FUNDING: Teva Pharmaceutical Industries, Israel.

The human gut microbiota and depression: widely reviewed, yet poorly understood.

BACKGROUND: A large number of existing reviews have discussed the role of the gut microbiota in affective disorders, though syntheses have been overwhelmingly narrative in their focus. METHOD: In this correspondence, we compliment Sanada et al. (2020) on their recent systematic review of the gut microbiota in Major Depressive Disorder (MDD), the first to incorporate a meta-analysis. We also comment on how this synthesis should be extended in future research. RESULTS: Sanada et al. (2020) conducted a meta-analysis of alpha diversity in participants with MDD compared to controls, whereby they unexpectedly observed no significant difference between groups. A meta-analysis was only able to be performed on alpha diversity indices. Future research should consider research quality, other forms of depression, incorporate comprehensive meta-analyses, where possible, as well as investigate associations between anxiety/depression symptom measures and the gut microbiota. LIMITATIONS: Further consideration of papers which incorporate functional analyses (e.g., metabolomics) is required to integrate this body of literature. CONCLUSIONS: Research investigating the microbiota-gut-brain axis in affective disorders has been met with great enthusiasm, offering promising direction for novel therapeutics in conditions such as depression. We encourage further systematic reviews in this space, particularly which consider research quality and incorporate comprehensive meta-analyses.

Feeling down? A systematic review of the gut microbiota in anxiety/depression and irritable bowel syndrome.

Background Anxiety/depression and irritable bowel syndrome (IBS) are highly prevalent and burdensome conditions, whose co-occurrence is estimated between 44 and 84%. Shared gut microbiota alterations have been identified in these separate disorders relative to controls; however, studies have not adequately considered their comorbidity. This review set out to identify case-control studies comparing the gut microbiota in anxiety/depression, IBS, and both conditions comorbidly relative to each other and to controls, as well as gut microbiota investigations including measures of both IBS and anxiety/depression. Methods Four databases were systematically searched using comprehensive search terms (OVID Medline, Embase, PsycINFO, and PubMed), following PRISMA guidelines. Results Systematic review identified 17 studies (10 human, 7 animal). Most studies investigated the gut microbiota and anxiety/depression symptoms in IBS cohorts. Participants with IBS and high anxiety/depression symptoms had lower alpha diversity compared to controls and IBS-only cohorts. Machine learning and beta diversity distinguished between IBS participants with and without anxiety/depression by their gut microbiota. Comorbid IBS and anxiety/depression also had higher abundance of Proteobacteria, Prevotella/Prevotellaceae, Bacteroides and lower Lachnospiraceae relative to controls. Limitations A large number of gut microbiota estimation methods and statistical techniques were utilized; therefore, meta-analysis was not possible. Conclusions Well-designed case-control and longitudinal studies are required to disentangle whether the gut microbiota is predicted as a continuum of gastrointestinal and anxiety/depression symptom severity, or whether reported dysbiosis is unique to IBS and anxiety/depression comorbidity. These findings may inform the development of targeted treatment through the gut microbiota for individuals with both anxiety/depression and IBS.

Oral microbiome composition, but not diversity, is associated with adolescent anxiety and depression symptoms.

PURPOSE: Depression and anxiety are highly prevalent disorders, whose significant burden is compounded by the presence of oral disease. Mental health disorders and oral health may be associated via changes to the oral microbiome, involving increased pro-inflammatory communication and cortisol in saliva. The present study provides the first culture-independent investigation of the oral microbiome considering depression and anxiety symptoms in adolescence, a critical age where these conditions begin to emerge and co-occur. It also investigates whether inflammation and cortisol moderate these relationships. METHODS: Participants (N = 66) aged 14-18 years (69.70% female) self-reported oral health, depression and anxiety symptoms, and collected saliva samples across two days. Saliva was assayed for cortisol and C-reactive protein (CRP), and used for 16S rRNA gene sequencing to estimate the oral microbiome. Multivariate statistical analyses examined associations. RESULTS: Overall diversity of the oral microbiome did not differ between adolescents by anxiety or depression grouping (low versus high symptoms), and was not associated with symptom measures. Depression and anxiety symptoms were instead associated with differential abundance of specific bacterial taxa, including Spirochaetaceae, Actinomyces, Treponema, Fusobacterium and Leptotrichia spp. Several host mood-microbial relationships were moderated by proposed mechanisms, including salivary cortisol and CRP. CONCLUSIONS: Oral microbiome composition, but not diversity, was associated with adolescent anxiety and depression symptoms. Longitudinal studies considering these associations would improve mechanistic understanding. This research indicates that adolescence remains an essential developmental period to identify early targets for intervention.

Prevalence of multiple sclerosis in Buenos Aires, Argentina using the capture-recapture method.

BACKGROUND: Scarce data exist about multiple sclerosis (MS) prevalence in South America. The objective of the study is to determine the prevalence of MS in a high populated area from Argentina (Greater Buenos Aires Metropolitan area) using the capture-recapture methodology. METHODS: Greater Buenos Aires is the generic denomination that refers to the megalopolis comprised by the autonomous city of Buenos Aires and the surrounding conurbation of the province of Buenos Aires. The study was carried out taking July 1996 as the prevalence month. We used capture-recapture method to estimate the prevalence of MS cross matching registries from four MS Centers. RESULTS: A total of 803 registries were obtained from the four lists. Log-linear model for capture-recapture method was used to analyze the data. The population of the area based on the 1990 census was 12,594,974; the number of MS cases estimated amongst sources interactions were between 1833 and 2359; the prevalence estimated ranged from 14 to 19.8 cases per 100,000 inhabitants. CONCLUSIONS: This is the first study to provide epidemiological data on the prevalence of MS in a large population in Argentina (Greater Buenos Aires Metropolitan area). Further epidemiological studies will clarify the true prevalence of MS in South America.

Therapeutic outcome 3 years after switching of immunomodulatory therapies in patients with relapsing-remitting multiple sclerosis in Argentina.

Switching treatment may be beneficial in patients with relapsing-remitting multiple sclerosis (RRMS) who respond inadequately to first-line immunomodulatory therapy. The objective of this study was to evaluate clinical outcomes after switching treatment in such patients. This prospective longitudinal observational study included 114 patients with RRMS who failed first-line monotherapy and were switched treatments after 3 years. Every 3 months, patients underwent a full neurological examination. Outcome was compared between the 3-year Before Switch and After Switch treatment periods. The primary outcome measure was the annualized relapse rate; secondary outcome measures were the proportion of relapse-free patients and the median change in Expanded Disability Status Scale (EDSS). Patients were switched either from low-dose to high-dose interferon-beta (IFNbeta; n = 31), from IFNbeta to glatiramer acetate (GA; n = 52) or mitoxantrone (n = 13), or from GA to IFNbeta (n = 16). In 3 years after switching, annualized relapse rates fell by 57-78% according to the group. The proportion of relapse-free patients varied from 56% to 81%. Least improved was observed in patients switching between INFbeta preparations. Median EDSS scores remained stable in all groups except the GA to IFNbeta switchers. In conclusion, patients who fail first-line immunomodulatory therapy generally benefit from switching to another class of immunomodulatory therapy.

Differential diagnosis of multiple sclerosis in Latin America.

Improvement of multiple sclerosis (MS) diagnoses leads to earlier and correct disease management. The differential diagnostic workup for MS comprises a large variety of medical conditions. There are general guidelines and criteria for diagnosing MS worldwide, but awareness of regional differences needs to be kept in mind. Latin American patients who are screened for MS diagnoses may require an approach that is not exactly the same as that used for patients in North America, western Europe or Asia. In the present review, the conditions that are important for the differential diagnoses of MS in Latin America are reviewed. They include infections, metabolic diseases, nutritional deficits and other autoimmune conditions that physicians in charge of these patients need to be familiar with.

Gender ratio trends over time in multiple sclerosis patients from Argentina.

Several studies in multiple sclerosis (MS) suggest a trend of increasing disease frequency in women during the last decades. A direct comparison of gender ratio trends among MS populations from Argentina remains to be carried out. The objective of the study was to compare gender ratio trends, over a 50-year span in MS populations from Argentina. METHODS: multicenter study that included patients from 14 MS Centers of Argentina. Patients with definite MS with birth years ranging from 1940 to 1989 were included. Gender ratios were calculated by five decades based on year of birth and were adjusted for the F/M born-alive ratio derived from the Argentinean national registry of births. The F/M ratios were calculated using a multivariate logistic regression per five decades by the year of birth approach. Analyses were performed using Stata 10.1. RESULTS: 1069 patients were included. Gender ratios showed a significant increase from the first to the last decade in the whole MS sample (from 1.8 to 2.7; p value for trend=0.023). The Gender ratio did not show differences considering MS subtype. CONCLUSION: our study showed a modest increase of the F/M ratio (from 1.8 to 2.7) over time among patients affected by MS in Argentina.

[The treatment of multiple sclerosis in Latin America: current practice and optimal standards. The findings of a survey among neurologists at an interactive workshop]. / Tratamiento de la esclerosis múltiple en Latinoamérica: práctica actual y estándares óptimos. Resultados de una encuesta a neurólogos durante un taller interactivo.

INTRODUCTION: Considerable progress has been made in the treatment of patients with relapsing-remitting multiple sclerosis (MS) over the last decade. Exactly how these changes are reflected in daily practice, however, is still not very well known. AIM: To hold interactive workshops so as to be able to evaluate the opinions of Latin-American neurologists about the therapeutic decisions taken with regard to MS. MATERIALS AND METHODS: By means of an interactive voting system, professionals attending each workshop replied to ten pre-established questions about when to start treatment, the use of magnetic resonance imaging (MRI) to supervise treatment, the definition of therapeutic failure and the role of treatment using immunosuppressants. The results were compared with those obtained in similar workshops attended by European and North American neurologists held six months earlier. RESULTS: The use of immunomodulators was considered to be useful in isolated demyelinating syndromes, as 40-50% endorsed their use in clinically stable patients. MRI was seen to be the most sensitive method of monitoring the effectiveness of the therapy -70.6% of them proposed the application of annual scans, which suggests a more frequent use in Latin America than in Europe or the USA. On defining therapeutic failure, the clinical criteria were more important than the MRI scan, and a switch from beta interferons to glatiramer acetate or vice versa was recommended. Treatment with immunosuppressants was considered to be useful in reducing the accumulated disability, but there was no agreement on how to use them. In Latin America, decisions about when to begin treatment seem to lie somewhere between the more favourable posture adopted in USA and the more conservative stance in Europe. CONCLUSIONS: This survey reflects the controversies that affect the therapeutic decisions concerning MS in Latin America and highlights the areas in which more data are needed to optimise the standards of treatment.

Increasing prevalence of multiple sclerosis in Buenos Aires, Argentina.

UNLABELLED: In 1996, the prevalence of multiple sclerosis (MS) for the metropolitan area of Buenos Aires using the capture-recapture method was estimated to be between 14 and 19.8 cases per 100,000 inhabitants. The aim of this study was to update the prevalence to 2014 following the same methodology. METHODS: Gran Buenos Aires is the denomination that refers to the megalopolis comprised by the autonomous city of Buenos Aires and the surrounding conurbation of the province of Buenos Aires. The study was carried out taking December 2014 as the prevalence month. We used the capture-recapture method to estimate the prevalence of MS cross-matching registries from 6 MS Centers from the metropolitan area of Buenos Aires. Log-linear model Poisson regression was used to estimate the number of affected MS patients not detected by any of the 6 sources considered. RESULTS: 1035 registries were obtained from the 6 lists from 910 different patients detected. The population of the area based on 2010 census was 12,806,866, the number of MS cases estimated amongst source interactions were 4901. The estimated prevalence was 38.2 per 100,000 inhabitants (95% CI 36.1-41.2). CONCLUSION: The study is an update almost 20 years after the first one in the area showing a significant increase in the previous reported prevalence. Our findings are in line with previous studies performed in other regions of the world.

Disease onset in familial and sporadic multiple sclerosis in Argentina.

UNLABELLED: The present study was carried out to assess if there is an anticipation of age at onset in younger generations of familial multiple sclerosis (FMS) vs. sporadic MS (SMS) in Argentina. METHODS: multicenter study that included patients from 14 MS Centers of Argentina. Patients were considered as FMS if they had in their family at least one relative of first or second degree diagnosed with MS; otherwise, patients were considered to have SMS. We compared the age at onset between familial and sporadic cases as well as the age at onset between relatives from different generations in FMS vs. SMS. RESULTS: 1333 patients were included, 97 of them were FMS (7.3%). A lower age at onset in the younger generations of FMS cases was found compared with older generations of FMS as well as. SMS cases (24.1±3.7 years vs. 30.3±5.7 years, and 32.4±9.4 respectively; p<0.001). No differences were observed between older generations of FMS vs. SMS cases (p=0.12). CONCLUSION: we observed an anticipation of age at onset of MS in younger generations of patients with FMS vs. older generations of FMS and SMS.

Improved serological diagnosis of Poplar mosaic virus with monoclonal antibodies.

Poplar mosaic virus (PopMV) is widespread in all countries where poplar is grown, and causes severe economic losses in terms of quantity and quality of wood production. Control is based on indexing, aimed at the production of healthy propagation material. The currently used diagnostic method is double antibody sandwich (DAS) ELISA with polyclonal antibodies, which is relatively simple and inexpensive and more reliable than visual inspection of symptoms in the nurseries. However, this method also has disadvantages, mainly low sensitivity in relation to low concentration and irregular distribution of the virus in the plant. In this study, a new diagnostic method for PopMV based on production and use of a monoclonal antibody (Mab) in a triple antibody sandwich (TAS) ELISA, is presented. The TAS-ELISA with monoclonal antibodies was optimised by testing a range of reagent combinations and concentrations. PopMV was detected by the optimised TAS-ELISA with sensitivity more than 100 times higher than by DAS-ELISA with polyclonal antibodies. Six PopMV isolates from four European countries were detected with the same efficiency, indicating that no limitations to the practical use of the TAS-ELISA arise due to excessive epitope-specificity of the monoclonal antibody employed.

Infusion of donor-derived peripheral blood leukocytes after transplantation of cord blood progenitor cells can increase the graft-versus-leukaemia effect.

We describe the case of a child affected by acute lymphoblastic leukaemia who received adoptive immunotherapy after cord blood transplantation (CBT). The patient, transplanted in second relapse resistant to chemotherapy, still showed lung and costal leukaemic nodular lesions 2 months after CBT. For this reason, three infusions of donor peripheral blood leukocytes 1 x 10(7)/kg each were administered on days +60, +80 and +100. The procedure was well tolerated by both patient and donor, and a complete disappearance of the lung lesions was documented 2 months after the last infusion. The patient remains in continuous complete haematological remission 13 months after CBT. This experience suggests that adoptive immunotherapy may be safely employed after CBT in order to increase the contribution of immune-mediated anti-leukaemia effect.