Respuesta autoinmune en individuos infectados por el virus ZIKA (RAIZ) / Autoinmune response in people infected with ZIKA viruS (RAIZ)

En el presente artículo se presenta una revisión de los principales resultados del proyecto RAIZ, acrónimo de "Respuesta autoinmune en individuos infectados por el virus Zika", originado por dos eventos mutuamente relacionados, la asociación entre un virus emergente en el continente, el virus Zika (vZika), y una enfermedad neuromuscular poco prevalente en Colombia, el síndrome de Guillain-Barré. Después de la llegada del virus al país se observó que las zonas donde se reportaban brotes del virus, se documentaba un aumento en los casos de síndrome de Guillain-Barré y otros síndromes neurológicos, que generó un gran interés para entender los mecanismos subyacentes de la infección asociados con autoinmunidad neurológica. Mediante la realización del primer estudio de casos y controles de Zika, Guillain-Barré y otros síndromes neurológicos, se comprobó dicha asociación en Colombia. A lo largo del proyecto, además, se investigaron los principales mecanismos asociados, mediante estudios de seroprevalencia de otras infecciones, inmunológicos y genéticos

This article presents a review of the main results of the RAIZ project, acronym of "Autoimmune response in individuals infected with the Zika virus", originated by two mutually related events: the association between an emerging virus on the continent, the Zika virus (vZika), and a neuromuscular disease not very prevalent in Colombia, the Guillain-Barré syndrome. After the arrival of the virus in the country it was observed that in the areas of outbreaks an increase of cases of Guillain-Barré syndrome and other neurological syndromes was documented, which generated a great interest in the understanding of the underlying mechanisms of the infection associated with neurological autoimmunity. By conducting the first case-control study on Zika, Guillain-Barré and other neurological syndromes in Colombia, the association was verified. Throughout the project, the main associated mechanisms were addressed through analyses of other infections, immunological analysis and the first genome-wide association study

A comprehensive analysis and immunobiology of autoimmune neurological syndromes during the Zika virus outbreak in Cúcuta, Colombia.

We have focused on the epidemiology and immunobiology of Zika virus (ZIKV) infection and factors associated with the development of Guillain-Barré syndrome (GBS) and other neurological syndromes in Cúcuta, the capital of North Santander department, Colombia. Data of patients with ZIKV disease reported to the national population-based surveillance system were used to calculate the basic reproduction number (R0) and the attack rates (ARs) as well as to develop epidemiological maps. Patients with neurological syndromes were contacted and their diagnoses were confirmed. A case-control study in which 29 patients with GBS associated with ZIKV compared with 74-matched control patients with ZIKV infection alone was undertaken. Antibodies against arboviruses and other infections that may trigger GBS were evaluated. The estimated value of R0 ranged between 2.68 (95% CI 2.54-2.67) to 4.57 (95% CI 4.18-5.01). The sex-specific ARs were 1306 per 100,000 females, and 552 per 100,000 males. A non-linear interaction between age and gender on the ARs was observed. The incidence of GBS in Cúcuta increased 4.41 times secondary to ZIKV infection. The lag time between ZIKV infection and neurological symptoms was 7 days (interquartile range 2-14.5). Patients with GBS appeared to represent a lower socioeconomic status and were living near to environmentally contaminated areas. All GBS patients were positive for IgG antibodies against both ZIKV and Dengue virus, and 69% were positive for Chikungunya virus. Noteworthy, GBS was associated with a previous infection with M. pneumoniae (OR: 3.95; 95% CI 1.44-13.01; p = 0.006). No differences in antibody levels against C. jejuni, Epstein-Barr virus and cytomegalovirus were observed. High rates of cranial nerves involvement and dysautonomia were present in 82% and 75.9%, respectively. Intensive care unit (ICU) admission was necessary in 69% of the GBS patients. Most of the patients disclosed a high disability condition (Hughes grade 4). Dysautonomia was the main risk factor of poor GBS prognosis (i.e., ICU admission and disability). Thirteen patients were diagnosed with other neurological syndromes different to GBS (6 with transverse myelitis, 3 with encephalitis, 3 with peripheral facial palsy and one with thoraco-lumbosacral myelopathy). Our data confirm an increased transmission of ZIKV in Cúcuta, and provide support to the view that severe neurological syndromes are related to ZIKV disease. The complex ways by which previous infections and socioeconomic status interact to increase the risk of GBS in people infected by ZIKV should be further investigated.

Guillain-Barré syndrome in Colombia: where do we stand now?

Guillain-Barré syndrome (GBS) is a rapid-onset muscle weakness disease caused by the immune-mediated damage of the peripheral nervous system. Since there is an increase incidence of GBS cases in Latin America, particularly in Colombia, and most of them are currently preceded by Zika virus (ZIKV) infection, we aimed to assess the available evidence of the disease in Colombia through a systematic literature review. Out of 51 screened abstracts, only 16 corresponded to articles that met inclusion criteria, of which 15 were case reports or case series. A total of 796 cases of GBS were reported in the included articles. The majority of patients were males (66.8 %) and younger than 50 years old (94 %). An infectious disease before the onset of GBS was registered in 31 % of patients, with gastrointestinal or respiratory symptoms being the most frequently observed. In those cases in which electrodiagnostic tests were performed, the most common subphenotype was acute inflammatory demyelinating polyneuropathy (17 %). Death was reported in 15 % of patients. Data regarding GBS in Colombia is scant and heterogeneous. Taking into account the burden of the disease and the recent rise of GBS cases associated with ZIKV, a careful patient evaluation and a systematic collection of data are warranted. A form to data gathering is proposed.

Presentación de una paciente con síndrome de Morgagni-Stewart-Morel / Presentation of a Patient with Morgagni-Stewart-Morel Syndrome

El síndrome de Morgagni-Stewart-Morel es una rara enfermedad que se caracteriza por hiperostosis frontal interna bilateral asociada a alteraciones metabólicas, psiquiátricas, hipertensión arterial y disfunción de pares craneales de etiología no definida. Se presentó una paciente femenina de 73 años, hipertensa, diabética, obesa, con trastornos psiquiátricos; padeciendo de cefalea, hiposmia e hipoacusia y se constató tomográficamente el engrosamiento frontal interno en relación con el estadio A de la clasificación de Hershkovitz de dicha enfermedad.

Morgagni-Stewart-Morel Syndrome is a rare disease characterized by bilateral hyperostosis frontalis interna associated to metabolic and psychiatric disorders, with hypertension and cranial nerve dysfunction of undefined etiology. A female patient of 73 years, hypertensive, diabetic, obese, was presented with psychiatric disorders; suffering from headache, hyposmia and hearing loss. In the tomographic study a stage A of Hershkovitz classification of the disease was found.

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.

Polineuropatía y miopatía en el paciente crítico revisión de la literatura / Polyneuropathy and myopathy in critically ill patients - a literature review

La polineuropatía y la miopatía del paciente crítico son complicaciones frecuentes en la UCI que se caracterizan por debilidad muscular generalizada incluyendo la limitación en el destete de la ventilación mecánica, prolongando la estancia hospitalaria y el riesgo de otras complicaciones. Causan discapacidad crónica en los sobrevivientes de la enfermedad crítica debido a cambios funcionales y estructurales en las fibras nerviosas y musculares resultando en la degeneración del nervio axonal, pérdida de miosina del músculo, hipoxia celular y necrosis muscular, lo que conduce a la inexcitabilidad eléctrica de nervios y músculos, con debilidad muscular reversible. El diagnóstico se realiza mediante la clínica, estudios electrofisiológicos y biopsia muscular. El control metabólico y de factores de riesgo reducirian la gravedad de las complicaciones y la rehabilitación temprana en la unidad podría acelerar la recuperación funcional y la independencia de los pacientes...

Critical illness polyneuropathy and myopathy are frequent complications in patients admitted to the ICU distinguished by generalized muscle weakness which hinders weaning from mechanical ventilation thus prolonging length of hospitalization and posing a higher risk of other complications. They cause chronic disability in survivors of critical illness due to functional and structural changes in nervous and muscular fibers resulting in axonal degeneration, loss of myosin filaments, cell hypoxia and muscle necrosis leading to nerve and muscle electrical inexcitability causing reversible muscle weakness. Clinical features and electrophysiologic testing or muscle biopsy are the gold standard for diagnosis. Controlling metabolic factors and risk factors could reduce serious complications and rehabilitation at an early stage of the ICU stay could improve functional recovery and patient independence...

Miopatía y mononeuritis múltiple asociadas con mieloma múltiple / Myopathy and multiplex mononeuritis associated to multiple myeloma

El mieloma múltiple (MM) hace parte del grupo de las gammapatías monoclonales y es el resultado de la proliferación maligna de un clon de células plasmáticas. La neoplasia por sí misma, sus productos metabólicos y la respuesta inmunológica del huésped son responsables de las manifestaciones clínicas que comprenden: el compromiso óseo, la susceptibilidad a infecciones, la retención de nitrogenados, anemia e hipercalcemia y manifestaciones neurológicas diversas. El compromiso del sistema nervioso central está dado por la presencia de plasmocitomas, mielomatosis leptomeníngea y síndrome de hiperviscosidad. Las manifestaciones relacionadas con el sistema nervioso periférico incluyen dolor lumbar asociado a radiculopatía y fracturas espinales al igual que compromiso motor y sensitivo resultante de la afección del nervio periférico y del músculo; estos últimos se producen por múltiples factores como alteraciones metabólicas, efectos adversos debidos al tratamiento de la enfermedad o a la presencia de infecciones oportunistas. Parte de la etiología del compromiso neuromuscular se explica también por factores inmunológicos propios de la enfermedad que generan anticuerpos contra los componentes estructurales, capaces de desencadenar las manifestaciones clínicas. Informamos un caso donde las manifestaciones neurológicas conducen al diagnóstico de mieloma múltiple; es llamativa la presentación en forma de mononeuritis múltiple y compromiso miopático, hallazgos poco frecuentes en esta entidad. Se plantea la etiología inmune como el factor desencadenante de las manifestaciones clínicas.

Criptococosis ocasionada por crytococcus neoformans variedad gatti / Cryptococcosis for crytococcus neoformans var. gatti

Introducción y objetivo: Cryptococcus neoformans, agente etiológico de la criptococosis presenta dos variedades (neoformans y gattii), las cuales causan diferentes formas clínicas, específicas para la variedad. Estas diferencias tienen relación con el hospedero, su respuesta inmune, los hallazgos clínicos, paraclínicos y de evolución. El objetivo del trabajo fue establecer las características clínicas y de laboratorio en pacientes colombianos afectados por la var. gattii, destacando su morbimortalidad. Diseño: estudio observacional descriptivo. Métodos: se analizaron las historias de 20 pacientes con afección sistémica por C. neoformans var. gattii diagnosticados entre 1988 y 1999. Se consignaron los datos demográficos, la procedencia, la información clínica, la evolución, las secuelas y el tratamiento. Resultados: quince pacientes fueron hombres y cinco mujeres, con edad promedio de 32 años; cuatro de ellos eran menores de 12 años. Los pacientes procedían de ocho departamentos; 12 de ellos de Norte de Santander. Los síntomas meníngeos motivaron la consulta en 18 pacientes y la afección pulmonar (criptococoma) en los dos restantes pero, posteriormente, éstos presentaron compromiso meníngeo. Los síntomas predominantes (más del 55 por ciento) fueron cefalea, vómito y fiebre. El 80 por ciento de los pacientes fueron considerados inmunocompetentes. El curso de la enfermedad fue severo ya que siete (35 por ciento) pacientes murieron un mes después del diagnóstico y otros siete sufrieron pérdida de la agudeza visual y/o de la visión. Conclusiones: se destaca la severidad de la afección por la var. gattii, su mortalidad y la morbilidad, lo cual señala la necesidad de un pronto diagnóstico de la variedad infectante de C. neoformans.