Diagnostic characteristics of Xpert MTB/RIF assay for the diagnosis of tuberculous meningitis and rifampicin resistance in Southern Brazil.

BACKGROUND: The timely diagnosis of tuberculous meningitis (TBM) is challenging. Molecular diagnostic tools are necessary for TBM, particularly in low- and middle-income countries. OBJECTIVES: We aimed to calculate the diagnostics characteristics of Xpert MTB/RIF for the detection of Mycobacterium tuberculosis in the cerebrospinal fluid (CSF) and the frequency of rifampicin (RIF)-resistance in the CSF samples. METHODS: A total of 313 consecutive CSF samples were studied and categorized into TBM definite, probable, possible, or not TBM cases based on the clinical, laboratory, and imaging data. RESULTS: For the definite TBM cases (n=7), the sensitivity, specificity, efficiency, and positive likelihood ratio were 100, 97, 97, and 38%, respectively. However, for the TBM definite associated with the probable cases (n=24), the sensitivity decreased to 46%. All CSF samples that were Xpert MTB/RIF-positive were RIF susceptible. CONCLUSION: Xpert MTB/RIF showed high discriminating value among the microbiology-proven TBM cases, although the values for the probable and possible TBM cases were reduced. Xpert MTB/RIF contributes significantly to the diagnosis of TBM, mainly when coupled with the conventional microbiological tests and clinical algorithms.

Diagnostic characteristics of Xpert MTB/RIF assay for the diagnosis of tuberculous meningitis and rifampicin resistance in Southern Brazil / Características diagnósticas do Xpert MTB/RIF para o diagnóstico de meningite tuberculosa e resistência à rifampicina no Sul do Brasil

ABSTRACT Background: The timely diagnosis of tuberculous meningitis (TBM) is challenging. Molecular diagnostic tools are necessary for TBM, particularly in low- and middle-income countries. Objectives: We aimed to calculate the diagnostics characteristics of Xpert MTB/RIF for the detection of Mycobacterium tuberculosis in the cerebrospinal fluid (CSF) and the frequency of rifampicin (RIF)-resistance in the CSF samples. Methods: A total of 313 consecutive CSF samples were studied and categorized into TBM definite, probable, possible, or not TBM cases based on the clinical, laboratory, and imaging data. Results: For the definite TBM cases (n=7), the sensitivity, specificity, efficiency, and positive likelihood ratio were 100, 97, 97, and 38%, respectively. However, for the TBM definite associated with the probable cases (n=24), the sensitivity decreased to 46%. All CSF samples that were Xpert MTB/RIF-positive were RIF susceptible. Conclusion: Xpert MTB/RIF showed high discriminating value among the microbiology-proven TBM cases, although the values for the probable and possible TBM cases were reduced. Xpert MTB/RIF contributes significantly to the diagnosis of TBM, mainly when coupled with the conventional microbiological tests and clinical algorithms.

RESUMO Introdução: O diagnóstico da meningite tuberculosa (TBM) é desafiador. Ferramentas de diagnóstico molecular são necessárias para esse diagnóstico, particularmente em países de baixa e média renda. Objetivos: Calcular as características diagnósticas do Xpert MTB/RIF para a detecção de Mycobacterium tuberculosis no líquido cefalorraquidiano (LCR) e a frequência de resistência à rifampicina (RIF) nas amostras do LCR. Métodos: Um total de 313 amostras consecutivas de LCR foram estudadas e categorizadas em casos de TBM definida, provável, possível ou não TBM, com base nos dados clínicos, laboratoriais e de imagem. Resultados: Para os casos definidos de TBM (n=7), sensibilidade, especificidade, eficiência e razão de verossimilhança positiva foram de 100, 97, 97 e 38%, respectivamente. No entanto, para os casos de TBM definidos associados aos prováveis (n=24), a sensibilidade diminuiu para 46%. Todas as amostras de LCR que foram positivas para Xpert MTB/RIF foram suscetíveis a RIF. Conclusão: O Xpert MTB/RIF mostrou alto valor discriminante entre os casos TBM comprovados por microbiologia, porém o valor nos casos prováveis e possíveis de TBM foram reduzidos. O Xpert MTB/RIF contribui significativamente para o diagnóstico de TBM, principalmente quando associado aos testes microbiológicos convencionais e algoritmos clínicos.

Uso prático da AbobotulinumtoxinA no tratamento de espasticidade em crianças com paralisia cerebral / Practical use of AbobotulinumtoxinA for the treatment of spasticity in children with cerebral palsy

AbobotulinumtoxinA (ABO) tem sido utilizada para o tratamento da espasticidade em crianças com paralisia cerebral (PC). Seu uso requer uma administração cuidadosa, quanto à dosagem, seleção de locais de aplicação, intervalo entre aplicações, eficácia e segurança. Este foi o primeiro painel de especialistas no tratamento da espasticidade que desenvolveu um guia sobre questões gerais relacionadas a terapêutica de médicos que utilizam ABO, incluindo a indicação da dosagem a ser aplicada por músculo. O tratamento deve ser iniciado o mais rápido, idealmente entre dois e seis anos de idade. Uma avaliação clínica deve identificar os músculos espásticos e determinar o objetivo: melhora funcional, analgesia, facilidade de cuidados e posicionamento, prevenção da luxação dos quadris, melhora da marcha e postura, facilitação do processo de educação, maior participação social e/ou melhora estética. Os pré-requisitos para alcançar bons resultados são a seleção muscular adequada, a dosagem de ABO e a técnica de injeção. Muitos padrões patológicos comuns podem ser tratados se vários músculos forem simultaneamente injetados em uma única sessão de tratamento; O planejamento da dose de ABO por músculo deve levar em consideração a dosagem máxima em unidades por músculo e a dose de ABO máxima total por sessão (30 U / kg de peso corporal do paciente, não superior a 1000 U). Após a aplicação, as crianças devem ser submetidas a programas de fisioterapia e terapia ocupacional, focadas em orientações domiciliares e em orientações para a família, aumentando as chances de ganho terapêutico. O tratamento com ABO é multidisciplinar e requer abordagens integradas

AbobotulinumtoxinA (ABO) has been used for the treatment of spasticity in children with cerebral palsy (CP). Its use requires careful administration, regarding dosing, selection of local of application, interval between applications and efficacy and safety monitoring. This was the first panel of experts on the treatment of spasticity, which developed a guide to provide an overview on important issues related to therapeutic strategies adopted by physicians using ABO, including its dosage to be applied per muscle.Treatment should be initiated as soon as possible, ideally between two and six years old. A clinical evaluation should identify muscles presenting spastic activity, and determine desired outcome: improvement of function, esthetics/aspect, pain treatment, easing care and positioning, preventing hips dislocation, improvement of walking and posture, and to provide conditions for education and social participation. Pre-requisites to achieve good results are adequate muscle selection, adequate ABO dosage and exact injection technique. Many common pathological patterns can be adequately treated if several muscles are simultaneously injected in a single treatment session; planning ABO dosage per muscle should take into consideration the maximum dosage in units per muscle and the total maximum ABO dosage per session (30 U/kg patient´s body weight, not exceeding 1000 U).After application children should be submitted to physical therapy and occupational therapy, focused on home therapy, and family involvement, increasing chances of therapeutic gain. Treatment with ABO is multidisciplinary and requires integrated approaches

Long-term follow-up of four patients with Langer-Giedion syndrome: clinical course and complications.

Long-term observations of individuals with the so-called Langer-Giedion (LGS) or tricho-rhino-phalangeal type II (TRPS2) are scarce. We report here a on follow-up of four LGS individuals, including one first described by Andres Giedion in 1969, and review the sparse publications on adults with this syndrome which comprises ectodermal dysplasia, multiple cone-shaped epiphyses prior to puberty, multiple cartilaginous exostoses, and mostly mild intellectual impairment. LGS is caused by deletion of the chromosomal segment 8q24.11-q24.13 containing among others the genes EXT1 and TRPS1. Most patients with TRPS2 are only borderline or mildly cognitively delayed, and few are of normal intelligence. Their practical skills are better than their intellectual capability, and, for this reason and because of their low self-esteem, they are often underestimated. Some patients develop seizures at variable age. Osteomas on processes of cervical vertebrae may cause pressure on cervical nerves or dissection of cerebral arteries. Joint stiffness is observed during childhood and changes later to joint laxity causing instability and proneness to trauma. Perthes disease is not rare. Almost all males become bald at or soon after puberty, and some develop (pseudo) gynecomastia. Growth hormone deficiency was found in a few patients, TSH deficiency so far only in one. Puberty and fertility are diminished, and no instance of transmission of the deletion from a non-mosaic parent to a child has been observed so far. Several affected females had vaginal atresia with consequent hydrometrocolpos.