Status of the neuromyelitis optica spectrum disorder in Latin America.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) is an increasing diagnostic and therapeutic challenge in Latin America (LATAM). Despite the heterogeneity of this population, ethnic and socioeconomic commonalities exist, and epidemiologic studies from the region have had a limited geographic and population outreach. Identification of some aspects from the entire region are lacking. OBJECTIVES: To determine ethnic, clinical characteristics, and utilization of diagnostic tools and types of therapy for patients with NMOSD in the entire Latin American region. METHODS: The Latin American Committee for Treatment and Research in MS (LACTRIMS) created an exploratory investigational survey addressed by Invitation to NMOSD Latin American experts identified through diverse sources. Data input closed after 30 days from the initial invitation. The questionnaire allowed use of absolute numbers or percentages. Multiple option responses covering 25 themes included definition of type of practice; number of NMOSD cases; ethnicity; utilization of the 2015 International Panel criteria for the diagnosis of Neuromyelitis optica (IPDN); clinical phenotypes; methodology utilized for determination of anti-Aquaporin-4 (anti- AQP4) antibodies serological testing, and if this was performed locally or processed abroad; treatment of relapses, and long-term management were surveyed. RESULTS: We identified 62 investigators from 21 countries reporting information from 2154 patients (utilizing the IPDN criteria in 93.9% of cases), which were categorized in two geographical regions: North-Central, including the Caribbean (NCC), and South America (SA). Ethnic identification disclosed Mestizos 61.4% as the main group. The most common presenting symptoms were concomitant presence of optic neuritis and transverse myelitis in 31.8% (p=0.95); only optic neuritis in 31.4% (more common in SA), p<0.001); involvement of the area postrema occurred in 21.5% and brain stem in 8.3%, both were more frequent in the South American cases (p<0.001). Anti-AQP4 antibodies were positive in 63.9% and anti-Myelin Oligodendrocyte Glycoprotein (MOG) antibodies in 4.8% of total cases. The specific laboratorial method employed was not known by 23.8% of the investigators. Acute relapses were identified in 81.6% of cases, and were treated in 93.9% of them with intravenous steroids (IVS); 62.1% with plasma exchange (PE), and 40.9% with intravenous immunoglobulin-G (IVIG). Therapy was escalated in some cases due to suboptimal initial response. Respondents favored Rituximab as long-term therapy (86.3%), whereas azathioprine was also utilized on 81.8% of the cases, either agent used indistinctly by the investigators according to treatment accessibility or clinical judgement. There were no differences among the geographic regions. CONCLUSIONS: This is the first study including all countries of LATAM and the largest cohort reported from a multinational specific world area. Ethnic distributions and phenotypic features of the disease in the region, challenges in access to diagnostic tools and therapy were identified. The Latin American neurological community should play a determinant role encouraging and advising local institutions and health officials in the availability of more sensitive and modern diagnostic methodology, in facilitating the the access to licensed medications for NMOSD, and addressing concerns on education, diagnosis and management of the disease in the community.

Short-segment transverse myelitis lesions in a cohort of Latin American patients with neuromyelitis optica spectrum disorders.

STUDY DESIGN: Multicenter retrospective study. OBJECTIVES: The aim was to determine the frequency and magnetic resonance imaging (MRI) features of short-segment transverse myelitis (STM) in patients with neuromyelitis optica spectrum disorders (NMOSD) during a myelitis attack. SETTING: Latin American diagnostic centres (Neuroimmunology Unit). A multicenter study from Argentina, Brazil and Venezuela was performed. METHODS: Seventy-six patients with NMOSD were included. We analyzed 346 attacks and reviewed spinal cord MRIs performed within 30 days from spinal attack onset. Sagittal and axial characteristics on cervical and thoracic MRI (1.5 tesla) were observed. Demographics, clinical, serological, and disability data were collected. RESULTS: Among the 76 patients with NMOSD, isolated STM was observed in 8% (n = 6), multisegmental lesions (longitudinally extensive transverse myelitis (LETM) + STM) in 28% (n = 21; 13 had at least one STM), LETM in 42% (n = 32), and normal spinal MRI in 22% (n = 17). However, isolated STM was increased by 10% in patients with NMOSD with spinal lesions (6 out of 59) with mean attacks of 2.5 (±0.83) and last follow-up expanded disability status scale (EDSS) of 3.1 (±2.63). Positive aquaporin 4 antibodies (AQP4-ab) were found in 50%. Upper-cervical lesion was most frequently observed (5 out of 6). Myelitis was preceded by ON in all isolated patients with STM. Only one had a positive gadolinium lesion and none of these had asymptomatic spinal cord lesion. CONCLUSION: Isolated STM does not exclude NMOSD diagnosis. Therefore, APQ4-ab testing could be useful during a myelitis attack with STM.

Frequency of brain MRI abnormalities in neuromyelitis optica spectrum disorder at presentation: A cohort of Latin American patients.

BACKGROUND: Brain magnetic resonance imaging (BMRI) lesions were classically not reported in neuromyelitis optica (NMO). However, BMRI lesions are not uncommon in NMO spectrum disorder (NMOSD) patients. OBJECTIVE: To report BMRI characteristic abnormalities (location and configuration) in NMOSD patients at presentation. METHODS: Medical records and BMRI characteristics of 79 patients with NMOSD (during the first documented attack) in Argentina, Brazil and Venezuela were reviewed retrospectively. RESULTS: BMRI abnormalities were observed in 81.02% of NMOSD patients at presentation. Forty-two patients (53.1%) showed typical-NMOSD abnormalities. We found BMRI abnormalities at presentation in the brainstem/cerebellum (n = 26; 32.9%), optic chiasm (n = 16; 20.2%), area postrema (n = 13; 16.4%), thalamus/hypothalamus (n = 11; 13.9%), corpus callosum (n = 11; 13.9%), periependymal-third ventricle (n = 9; 11.3%), corticospinal tract (n = 7; 8.8%), hemispheric white matter (n = 1; 1.2%) and nonspecific areas (n = 49; 62.03%). Asymptomatic BMRI lesions were more common. The frequency of brain MRI abnormalities did not differ between patients who were positive and negative for aquaporin 4 antibodies at presentation. CONCLUSION: Typical brain MRI abnormalities are frequent in NMOSD at disease onset.

Consenso venezolano para el uso de la resonancia magnética en el diagnóstico y seguimiento de pacientes con esclerosis múltiple / Venezuelan consensus guidelines on the use of magnetic resonance in diagnosis and follow up of patients with multiple sclerosis

Introducción. El uso de la resonancia magnética (RM) en el diagnóstico y seguimiento de pacientes con esclerosis múltiple (EM) se ha incrementado considerablemente durante los últimos años. Diversos grupos de trabajo internacionales han intentado clarificar y normativizar el uso de la RM tanto en el momento del diagnóstico como durante el seguimiento de los pacientes. Sin embargo, en muchas ocasiones se extrapolan datos de otras regiones que no contemplan la realidad de cada lugar o son difíciles de implementar. Objetivo. Elaborar un consenso venezolano para el uso de la RM en el diagnóstico y seguimiento de pacientes con EM. Desarrollo. Un grupo de expertos de Venezuela, conformado por neurólogos y radiólogos, mediante metodología de ronda de encuestas a distancia y reuniones presenciales, llevó adelante la elaboración del consenso pretendido para el uso de la RM en el diagnóstico y seguimiento de pacientes con EM en Venezuela. Se establecieron 17 recomendaciones basadas en la evidencia publicada y en el criterio de los expertos que participaron. Las recomendaciones se enfocaron en el papel de las técnicas convencionales de RM, así como en el de la medición de la atrofia cerebral en pacientes con EM, tanto en el momento del diagnóstico como durante el seguimiento. Conclusión. Las recomendaciones establecidas en el presente consenso permitirán optimizar el cuidado y el seguimiento de los pacientes con EM en Venezuela (AU)

Introduction. The clinical use of magnetic resonance (MR) in patients with multiple sclerosis (MS) has advanced markedly over the past few years. Several groups around the world have developed consensus guidelines about the role of MR in MS at diagnosis and during follow up. However, in some regions is difficult to extrapolate the recommendations. Aim. To provide recommendations for the implementation of MR in MS patients at diagnosis and follow up in Venezuela. Development. A group of experts from Venezuela that included neurologists and radiologists, by using the online surveys methodology as well as face to face meetings developed the intended consensus for the use of MR during the diagnosis and follow up of MS patients in Venezuela. Seventeen recommendations were established based on published evidence and the expert opinion. Recommendations focused on the role of conventional MR techniques and brain atrophy measurement in MS patients both at diagnosis and during follow-up. Conclusions. The recommendations of this consensus guidelines attempts to optimize the health care and management of patients with MS in Venezuela (AU)

Calidad de las estadísticas de mortalidad en la provincia Camagüey según cuantificación de causas de muertes imprecisas / Quality of the statistics of mortality in Camagüey province according to quantification of imprecise causes of death

Fundamento: la certificación de las causas de muerte es uno de los procederes más antiguos que existen en la práctica médica. Una correcta certificación reviste una gran importancia pues a partir de su análisis se derivan acciones desde regionales hasta internacionales para a través de programas de salud elevar la calidad de vida de la población. Objetivo: evaluar la calidad de las estadísticas de mortalidad en la provincia Camagüey en los últimos 15 años, a partir de la cuantificación de causas básicas de muerte imprecisas o no deseadas consignadas en los certificados médicos de defunción. Métodos: se realizó un estudio descriptivo transversal retrospectivo de las estadísticas de mortalidad en la provincia Camagüey, que abarcó el universo de certificados médicos de defunción registrados entre los años 2000 y 2014. Se realizó una revisión documental y se definieron los indicadores de calidad por grupos de códigos asignados a la causa básica de muerte. Resultados: en la provincia Camagüey en los 15 años estudiados (2000-2014) ocurrieron 85 770 defunciones según residencia, de ellas el 6,74 % fueron codificadas con causa básica de muerte imprecisa o no deseada. El quinquenio 2005-2009 fue el de mayor incidencia en la certificación de este tipo de causa básica, con una tendencia al descenso para los últimos cinco años. Al analizar el valor puntual de los 15 años estudiados, solo en cinco la razón de cambio respecto al año índice (2000) fue superior a 1,30 o sea, que se incrementó en más de un 30 % respecto al año índice. Conclusiones: la certificación médica de las causas básicas de muerte imprecisas o indeseadas en la provincia Camagüey es baja y ha presentado una tendencia a la disminución en el último quinquenio.

Background: the certification of causes of death is one of the most ancient procedures in medical practice. A correct certification has a great importance since regional and international actions derive from its analysis for raising the quality of life of people by means of health programs. Objective: to asses the quality of the statistics of mortality in Camagüey province in the last 15 years from the quantification of undesirable or imprecise basic causes of death recorded on the medical death certificates. Method: a descriptive, cross-sectional, retrospective study of the statistics of mortality was conducted in the province of Camagüey including the universe of medical death certificates between the years 2000 and 2014. A documentary review was made and the quality indicators were defined by code groups assigned to the basic cause of death. Results: in Camagüey province, in the studied 15 years (2000-2014), 85 770 deaths happened according to residence; the 6, 74 % of them were codified as undesirable or imprecise basic cause of death. The five-year period 2005-2009 presented the greatest incidence in the certification of this type of basic cause with a tendency to increase in the last five years. Of the 15 years studied, in five years the ratio of change was higher than 1, 30 when analysing the precise value of every year with respect to the rate year (2000), i.e. that it increased in more than a 30 % with respect to the rate year. Conclusions: the medical certification of the undesirable or imprecise basic causes of death in Camagüey province is low and has presented a tendency to decrease in the last five-year period.

Calidad de las estadísticas de mortalidad en la provincia Camagüey según cuantificación de causas de muertes imprecisas / Quality of the statistics of mortality in Camagüey province according to quantification of imprecise causes of death

Fundamento: la certificación de las causas de muerte es uno de los procederes más antiguos que existen en la práctica médica. Una correcta certificación reviste una gran importancia pues a partir de su análisis se derivan acciones desde regionales hasta internacionales para a través de programas de salud elevar la calidad de vida de la población.Objetivo: evaluar la calidad de las estadísticas de mortalidad en la provincia Camagüey en los últimos 15 años, a partir de la cuantificación de causas básicas de muerte imprecisas o no deseadas consignadas en los certificados médicos de defunción.Métodos: se realizó un estudio descriptivo transversal retrospectivo de las estadísticas de mortalidad en la provincia Camagüey, que abarcó el universo de certificados médicos de defunción registrados entre los años 2000 y 2014. Se realizó una revisión documental y se definieron los indicadores de calidad por grupos de códigos asignados a la causa básica de muerte.Resultados: en la provincia Camagüey en los 15 años estudiados (2000-2014) ocurrieron 85 770 defunciones según residencia, de ellas el 6,74 porciento fueron codificadas con causa básica de muerte imprecisa o no deseada. El quinquenio 2005-2009 fue el de mayor incidencia en la certificación de este tipo de causa básica, con una tendencia al descenso para los últimos cinco años. Al analizar el valor puntual de los 15 años estudiados, solo en cinco la razón de cambio respecto al año índice (2000) fue superior a 1,30 o sea, que se incrementó en más de un 30 porciento respecto al año índice.Conclusiones: la certificación médica de las causas básicas de muerte imprecisas o indeseadas en la provincia Camagüey es baja y ha presentado una tendencia a la disminución en el último quinquenio (AU)

Background: the certification of causes of death is one of the most ancient procedures in medical practice. A correct certification has a great importance since regional and international actions derive from its analysis for raising the quality of life of people by means of health programs.Objective: to asses the quality of the statistics of mortality in Camagüey province in the last 15 years from the quantification of undesirable or imprecise basic causes of death recorded on the medical death certificates.Method: a descriptive, cross-sectional, retrospective study of the statistics of mortality was conducted in the province of Camagüey including the universe of medical death certificates between the years 2000 and 2014. A documentary review was made and the quality indicators were defined by code groups assigned to the basic cause of death.Results: in Camagüey province, in the studied 15 years (2000-2014), 85 770 deaths happened according to residence; the 6, 74 percent of them were codified as undesirable or imprecise basic cause of death. The five-year period 2005-2009 presented the greatest incidence in the certification of this type of basic cause with a tendency to increase in the last five years. Of the 15 years studied, in five years the ratio of change was higher than 1, 30 when analysing the precise value of every year with respect to the rate year (2000), i.e. that it increased in more than a 30 percent with respect to the rate year.Conclusions: the medical certification of the undesirable or imprecise basic causes of death in Camagüey province is low and has presented a tendency to decrease in the last five-year period (AU)

Central Nervous System Idiopathic Inflammatory Demyelinating Disorders in South Americans: A Descriptive, Multicenter, Cross-Sectional Study.

The idiopathic inflammatory demyelinating disease (IIDD) spectrum has been investigated among different populations, and the results have indicated a low relative frequency of neuromyelitis optica (NMO) among multiple sclerosis (MS) cases in whites (1.2%-1.5%), increasing in Mestizos (8%) and Africans (15.4%-27.5%) living in areas of low MS prevalence. South America (SA) was colonized by Europeans from the Iberian Peninsula, and their miscegenation with natives and Africans slaves resulted in significant racial mixing. The current study analyzed the IIDD spectrum in SA after accounting for the ethnic heterogeneity of its population. A cross-sectional multicenter study was performed. Only individuals followed in 2011 with a confirmed diagnosis of IIDD using new diagnostic criteria were considered eligible. Patients' demographic, clinical and laboratory data were collected. In all, 1,917 individuals from 22 MS centers were included (73.7% female, 63.0% white, 28.0% African, 7.0% Mestizo, and 0.2% Asian). The main disease categories and their associated frequencies were MS (76.9%), NMO (11.8%), other NMO syndromes (6.5%), CIS (3.5%), ADEM (1.0%), and acute encephalopathy (0.4%). Females predominated in all main categories. The white ethnicity also predominated, except in NMO. Except in ADEM, the disease onset occurred between 20 and 39 years old, early onset in 8.2% of all cases, and late onset occurred in 8.9%. The long-term morbidity after a mean disease time of 9.28±7.7 years was characterized by mild disability in all categories except in NMO, which was scored as moderate. Disease time among those with MS was positively correlated with the expanded disability status scale (EDSS) score (r=0.374; p=<0.001). This correlation was not observed in people with NMO or those with other NMO spectrum disorders (NMOSDs). Among patients with NMO, 83.2% showed a relapsing-remitting course, and 16.8% showed a monophasic course. The NMO-IgG antibody tested using indirect immunofluorescence (IIF) with a composite substrate of mouse tissues in 200 NMOSD cases was positive in people with NMO (95/162; 58.6%), longitudinally extensive transverse myelitis (10/30; 33.3%) and bilateral or recurrent optic neuritis (8/8; 100%). No association of NMO-IgG antibody positivity was found with gender, age at onset, ethnicity, early or late onset forms, disease course, or long-term severe disability. The relative frequency of NMO among relapsing-remitting MS (RRMS) + NMO cases in SA was 14.0%. Despite the high degree of miscegenation found in SA, MS affects three quarters of all patients with IIDD, mainly white young women who share similar clinical characteristics to those in Western populations in the northern hemisphere, with the exception of ethnicity; approximately one-third of all cases occur among non-white individuals. At the last assessment, the majority of RRMS patients showed mild disability, and the risk for secondary progression was significantly superior among those of African ethnicity. NMO comprises 11.8% of all IIDD cases in SA, affecting mostly young African-Brazilian women, evolving with a recurrent course and causing moderate or severe disability in both ethnic groups. The South-North gradient with increasing NMO and non-white individuals from Argentina, Paraguay, Brazil and Venezuela confirmed previous studies showing a higher frequency of NMO among non-white populations.

Management of relapsing-remitting multiple sclerosis in Latin America: practical recommendations for treatment optimization.

The Latin American MS Experts' Forum has developed practical recommendations on the initiation and optimization of disease-modifying therapies in patients with relapsing-remitting multiple sclerosis (RRMS). The recommendations reflect the unique epidemiology of MS and the clinical practice environment in Latin American countries. Treatment response may be evaluated according to changes in relapses; progression, as assessed by the Expanded Disability Status Scale and the Timed 25-foot Walk; and lesion number on magnetic resonance imaging. Follow-up assessments are recommended every six months, or annually for stable patients. Cognitive function should be evaluated in all RRMS patients at baseline and annually thereafter. These recommendations are intended to assist clinicians in Latin America in developing a rational approach to treatment selection and sequencing for their RRMS patients.

COX-2 and sPLA2 inhibitory activity of aqueous extract and polyphenols of Rhizophora mangle (red mangrove).

The aqueous extract of Rhizophora mangle bark and its polyphenolic fractions showed remarkable in vitro antiinflammatory activity in a preliminary study. The low molecular weight fraction exhibited cyclooxygenase-2 inhibitory activity while the total aqueous extract and the low molecular weight fraction showed secretory phospholipase A(2) inhibitory activity.

Efficacy of Rhizophora mangle aqueous bark extract (RMABE) in the treatment of aphthous ulcers: a pilot study.

OBJECTIVE: Rhizophora mangle aqueous bark extract (RMABE) (CIKRON-H), has been used as antiseptic and skin wound healing promoter. The present study was a randomised, single-blinded, placebo control trial conducted to asses the efficacy of RMABE in treating oral aphthous ulcers. RESEARCH DESIGN AND METHODS: Patients (n = 32) with aphthous ulcers were randomised to received placebo solution or RMABE topically, once a day, from Monday to Friday, until they healed. The efficacy of the treatment was evaluated by physician clinical observations (time to heal, change in condition), the quality of the patient's life and the tolerability through recording adverse effects. RESULTS: No demographic differences were noted between the two groups at base-line. Seven days after treatment, 12 of the 17 patients in the RMABE group (71%) were completely healed of their aphthous ulcers, with repaired mucosa and no symptoms of ulcers, compared with one in 15 patients in the placebo group (7%) (p < 0.0001). The time taken for the signs and symptoms of ulcers to diminish was also higher in the placebo than in RMABE-treatment group (erythema: placebo 10.54 +/- 1.24, RMABE 4.94 +/- 0.72 days, p = 0.0003; ardour: placebo 7.00 +/- 0.76, RMABE 2.93 +/- 0.49 days, p = 0.0001; and pain: placebo 7.43 +/- 1.21, RMABE 2.92 +/- 0.23 days, p = 0.0011). No subject showed any sign of adverse effects. CONCLUSIONS: These observations demonstrate that the R. mangle aqueous bark extract reduced the time to repair mucosal tissue, erythema, ardour and pain persistence. There was no evidence any adverse effects. This is the first time that the R. mangle extract has been reported to have mouth mucosa healing properties.

Prevalence of Candida albicans and Trichomonas vaginalis in pregnant women in Havana City by an immunologic latex agglutination test.

We aimed to estimate the prevalence of Candida albicans and Trichomonas vaginalis in immunocompetent pregnant women living in Havana City, Cuba, with or without symptoms of vaginitis, using a sample of 640 women from 6 Gyneco-obstetrics hospitals, which represents 2.5% of total yearly pregnant women. Diagnosis was made using a new latex agglutination kit (Newvagin C-Kure, La Habana, Cuba). Clinical sensitivity and specificity of this assay were validated against culture method, with 467 and 489 clinical specimens for Candida albicans and Trichomonas vaginalis, respectively. Results showed that the kit clinical sensitivity was 100% for Candida albicans and 86.7% for Trichomonas vaginalis compared with a clinical specificity of 93.3% for Candida albicans and 95.1% for Trichomonas vaginalis by culture. The prevalence of candidiasis was determined to be 42.3% (95% confidence interval [CI] 3.8%); the prevalence of trichomoniasis was 9.84% (95% CI 2.3%). In our sample, 48.7% of the women tested negative with respect to both candidiasis and trichomoniasis. Only 6.41% of the cases yielded inconclusive results. The test has high sensitivity, and our results indicate a relatively high prevalence of both infections. However, a significant difference (P < .001) was also observed in candidiasis and trichomoniasis prevalence among hospitals corresponding to the quantity of women with clinical vaginitis. No difference was observed between diabetics and nondiabetics, probably due to the special care of diabetic pregnant women. We conclude that the method is useful for this kind of vaginitis prevalence study and that candidiasis and trichomoniasis prevalences in pregnant women of Havana are 38.5% to 46.2 % (95% CI) and 7.5% to 12.1% (95% CI), respectively.

Diagnóstico de meningitis tuberculosa por la determinación de la actividad de adenosina deaminasa y la amplificación de secuencias nucleotídicas por PCR / Diagnosis of tubercular meningitis by detection of adenosine deaminase activity and amplification of nucleotide sequences with PCR

La tuberculosis meningea (TBM) es la forma más severa y letal de la tuberculosis. El diagnóstico bacteriológico rápido en TBM es casi imposible con los métodos convencionales. Por esto muchos pacientes son tratados con drogas anti-TBC sin tener un diagnóstico definitivo. Un método de diagnóstico más rápido y efectivo es necesario, para poder iniciar tratamiento a tiempo y evitar las secuelas neurológicas irreversibles o la muerte. En este trabajo se evaluó la actividad de la adenosina deaminasa (ADA) y amplificación de las secuencias IS6110 y mtp40 por reacción en cadena de la polimerasa (PCR), en líquido cerebroespinal de pacientes con meningitis crónica. Para la actividad de ADA > 8 U/L la sensibilidad fue de 80 por ciento y la especificidad de 91 por cieto. PCR para IS6110 mostró valores de sensibilidad de 80 por ciento y 97 por ciento de especificidad. La actividad de ADA y la PCR a partir de muestras de LCR son útiles como herramientas complementarias en el diagnóstico de TBM