Diabetes insipidus secondary to tuberculous meningoencephalitis with hypothalamic involvement extending to the hypophysis: a case report

Abstract The involvement of Mycobacterium tuberculosis in the central nervous system (CNS) is an uncommon and devastating manifestation of tuberculosis. We report a case of disseminated tuberculosis presenting as meningoencephalitis, hypothalamic involvement with extension to the hypophysis, and secondary insipidus diabetes diagnosed at autopsy.

Utilidad de la cuantificación de carga viral de VIH en líquido cefalorraquídeo, a propósito de un caso / Clinical utility of HIV viral load assessment in cerebral spinal fluid, a case report

Resumen La detección de virus en el líquido cefalorraquídeo (LCR) en pacientes infectados por VIH con carga viral (CV) indetectable en el plasma se ha denominado escape viral. Estas fugas pueden ser asintomáticas o asociadas con enfermedad neurológica. La discordancia de la carga viral de VIH entre plasma y LCR evidenciaría la presencia de distintos compartimentos del virus, con la posibilidad de identificar quasiespecies con mutaciones específicas que confieran resistencia a la TARV. Presentamos el caso clínico de un paciente con infección por VIH en etapa SIDA y una tuberculosis diseminada que presentó un cuadro neurológico manifestado por cefalea y un síndrome convulsivo, en que se encontró una discordancia entre la CV para VIH en plasma y LCR. El estudio genotípico del virus obtenido del LCR identificó nuevas mutaciones que determinaron un cambio de la TARV, con evolución posterior satisfactoria.

Detection of virus in cerebrospinal fluid (CSF) in HIV-infected patients with HIV viral load (VL) undetectable in plasma has been termed viral escape. These leaks may be asymptomatic from a neurological point of view, similar to plasma blips, or associated with neurological disease, with discordant VL between plasma and CSF, and may be evidence of a compartmentalization of the virus and the possibility of identifying quasispecies with mutations that confer resistance to ART. We present the case of a man with AIDS and disseminated tuberculosis who presented neurological symptomatology evidenced by headache and convulsive syndrome, who presented a discordance between plasma and CSF HIV VL; the genotypic test of the virus, obtained by lumbar puncture, identified new mutations that determined a change in ART with subsequent satisfactory evolution.

La gran simuladora: tuberculosis meníngea: caso clínico / The Great Simulator: Meningeal Tuberculosis: Clinical Case

La Tuberculosis (TB) es la enfermedad infec-to-contagiosa más importante del mundo, asociada a alta morbimortalidad, principal-mente es pulmonar, sin embargo puede afec-tar otros órganos y tejidos. La Organización Mundial de la Salud (OMS) 2015, estimó un millón de niños con TB en el mundo y 169,000 fallecidos. Según la OMS, Hondu-ras ocupa el octavo lugar en carga de tuber-culosis en el hemisferio occidental. Estos datos reflejan que continúa siendo un proble-ma de salud pública prioritario. En países de alta endemicidad, la principal barrera es la pobreza y el escaso acceso al sistema sani-tario. La incidencia de tuberculosis meníngea (TBM) se relaciona directamente con la prevalencia de TB pulmonar (TBP) y aunque solo representa alrededor del 1% de los casos de TB y 5%-10% de TB extrapulmonar, su presencia es preocupante por su elevada tasa de mortalidad (30%) en aquellos pacien-tes que reciben tratamiento óptimo y de secuelas graves en el 50% de los sobrevi-vientes, por lo que el factor más importante que influye en el pronóstico es el diagnóstico precoz y el inicio temprano de tratamiento específico. El diagnóstico de la TBM con frecuencia representa un desafío para el médico; se necesita un alto grado de sospe-cha clínica para no retrasar el diagnóstico y tratamiento puesto que el cuadro clínico es inespecífico, heterogéneo y aunque el examen del líquido cefalorraquídeo (LCR) aporta datos sugestivos, habitualmente se inicia tratamiento empírico sin tener certeza de que el diagnóstico será confirmado. Las The Great Simulator: Meningeal Tuberculosis: Clinical CaseLa Gran Simuladora: Tuberculosis Meníngea: Caso Clínicomanifestaciones clínicas y su duración son de vital importancia para su sospecha...(AU)

Tuberculous meningitis in childhood: new aspects of neurologic complications / Meningite tuberculosa na infância: novos aspectos das complicações neurológicas

Tuberculous Meningitis (TBM) is a severe manifestation of tuberculosis that represents 1% of the cases of infection by Mycobacterium tuberculosis. Children are among the other age groups the most affected and when present, HIV-1 is responsible for poorer prognosis. It was carried out a search on the databases of Pubmed, Lilacs and Scielo, looking for articles that approach the principals news aspects of neurologic complications caused by TBM. The literature cite as major neurologic findings the hydrocephalus in approximately 80% patients, meningeal irritation, coma, seizures, intracranial pressure signs, cranial nerve palsy, hemiparesis and disorders in the movement. Neurologic sequelae occur in up to 50% of survivors and early diagnosis is crucial to reduce the occurrence of major functional losses. In this way, discussions presenting more specific methods for TBM as well as better assessment of the signs and symptoms of the disease is necessary for a better prognosis and lower mortality rate of these patients.

A meningite tuberculosa (MTB) é uma manifestação grave da tuberculose que representa 1% dos casos de infecção por Mycobacterium tuberculosis. As crianças estão as faixas etárias mais afetadas e quando presente, o HIV-1 é responsável pelo pior prognóstico. Foi realizada uma revisão de bancos de dados Pubmed, Lilacs e Scielo, à procura de artigos que abordem os principais aspectos das complicações neurológicas causadas pela MTB. Os principais achados neurológicos compreendem a hidrocefalia em aproximadamente 80% dos pacientes, irritação meníngea, coma, convulsões, sinais de pressão intracraniana, paralisia de nervo craniano, hemiparesia e distúrbios movimento. Sequelas neurológicas ocorrem em até 50% dos sobreviventes e o diagnóstico precoce é crucial para reduzir a ocorrência de perdas. Desta forma, as discussões apresentando métodos mais TBM, bem como uma melhor avaliação dos sinais e sintomas da doença é necessária para um melhor prognóstico e menor taxa de mortalidade desses pacientes.

Tuberculous meningitis: a report of 60 adult cases / Meningitis tuberculosa: reporte de 60 casos adultos

OBJECTIVE: This was to evaluate the history, clinical and laboratory findings, outcome and prognosis of patients with tuberculous meningitis (TBM). METHOD: Between 1998 and 2009, 60 patients with TBM were evaluated, retrospectively. RESULT: Overall, 60 patients were selected, of which 33 (55%) were male. The patients' ages ranged from 14 to 62 years. In the majority of the patients, disease was in an advanced stage on admission (66% in stage III according to the British Research Council neurological criteria). The rate of complications was highest among patients in stages II and III with an overall mortality rate of 6.6% (n= 2 of stage II patients and n= 2 of stage III patients). CONCLUSIONS: Earlier admission of the patients with TBM could provide better outcomes with regard to sequelae and mortality. Fatal cases presented with rapid deterioration and were refractory to treatment.

OBJETIVO: El propósito de este trabajo fue evaluar la historia, los hallazgos clínicos y de laboratorio, la evolución, y la prognosis de pacientes con meningitis tuberculosa (MTB). MÉTODO: Entre 1998 y 2009, se evaluaron 60 pacientes con TBM, retrospectivamente. RESULTADOS: En general, se seleccionaron 60pacientes, de los cuales 33 (55%) fueron varones. La edad de los pacientes osciló de 14 a 62 años. En la mayoría de los pacientes, la enfermedad se encontraba en etapa avanzada al momento del ingreso (66% en la etapa III de acuerdo con los criterios neurológicos del Consejo Británico de Investigación). La tasa de complicaciones fue más alta entre los pacientes en las etapas IIy III con una tasa de mortalidad general de 6.6% (n = 2 en los pacientes de etapa IIy n = 2 en los pacientes de etapa III). CONCLUSIONES: El ingreso temprano de los pacientes con MTB podría proporcionar mejores resultados con respecto a las secuelas y la mortalidad. Los casos fatales se presentaron con deterioro rápido y fueron refractarios al tratamiento.

Meningitis y diseminación tuberculosa en paciente con el síndrome de inumodeficiencia adquirida (sida) / Meningitis and tuberculosis dissemination in acquired immunodeficiency syndrome (AIDS) patients

Las meningoencefalitis por gérmenes oportunistas ocupan un lugar importante dentro de la patología neurológica del paciente sida, Treponema pallidum y Mycobacterium tuberculosis dentro de las bacterias, Cryptococcus neoformans dentro de los hongos, Toxoplasma gondii dentro de los protozoos y el Papovirus JC dentro de los virus, son de los gérmenes mas frecuentes dentro de cada grupo. También en los pacientes inmunodeprimidos en general y en particular en el paciente sida, se han encontrado con cierta frecuencia infecciones mixtas, precisamente por el gran deterioro en su barrera inmunológica. La meningitis tuberculosa (MTB) es la forma mas grave en que se manifiesta la tuberculosis extrapulmonar, pues la inespecificidad de sus síntomas, la lentitud en el diagnóstico etiológico y las severas secuelas neurológicas que puede producir sobre todo en este tipo de paciente, hacen de esta enfermedad un importante problema de salud, tanto en países desarrollados como en los que están en vías de desarrollo. En este estudio se describe el ¨primer caso¨ meningitis e infección diseminada por Mycobacterium tuberculosis en paciente cubano infectado por el virus de inmunodeficiencia humana

Meningoencephalitis due to opportunistic germs has an important place among the neurological diseases in AIDS patient. Treponema pallidum and Mycobacterium tuberculosis (bacteria), Cryptococcus neoformans (fungi), Toxoplasma gondii (protozoa), and Papovirus JC (virus) are the most frequently germs found in each group. Likewise, in immunodepressed patients in general and in HIV/AIDS patients in particular, mixed infections have been frequently found, basically as a consequence of the patient’s deteriorated immunological barrier. Tuberculosis meningitis (TBM) is the most severe form of presentation of the extrapulmonary tuberculosis. Its unspecific symptoms, the delay in the etiological diagnosis, and the severe neurological sequelae that can appear in this specific type of patient make of this disease an important health problem, in both developed and developing countries. This study describes the "first case" of meningitis and disseminated infection by Mycobacterium tuberculosis in a Cuban patient infected by the human immunodeficiency virus

Profile of tuberculous meningitis with or without HIV infection and the predicators of adverse outcome / Perfil de la meningitis tuberculosa con o sin infección por VIH y predictores de la evolución clínica adversa

OBJECTIVES: To compare the clinical, radiological and cerebrospinal fluid (CSF) findings, at hospital admission, among adult patients with tuberculous meningitis (TBM) with or without HIV infection and to identify the factors that predict adverse outcome at six months. METHODS: A total of 82 adult patients with TBM were included (40 HIV-positive and 42 HIV-negative). Several clinical (duration of illness, Glasgow Coma Scale score, presence of high temperature, headache, cranial nerve or sphincter abnormality, seizures and endocrine dysfunction), radiological (presence of hydrocephalus, cerebral infarction and oedema, meningeal enhancement, granuloma) and cerebrospinal fluid parameters (glucose, protein, lactate, lymphocytes, neutrophils and adenosine deaminase values) were recorded along with CD4 count in the peripheral blood. Statistical analysis was performed using the chi-square test. Individual variables were evaluated as prognostic factors for adverse outcome in both groups by calculating the relative risk of association for each. RESULTS: Temperature more than 38.33ºC was more common in the HIV-negative group while seizures, hydrocephalus, cerebral infarction and low CD4 count occurred significantly more commonly in the HIV-positive group. Hydrocephalus had strong association with severe neurological deficit and seizure with death in both the groups. CONCLUSION: Several clinical and laboratory features of TBM in patients who are HIV-positive are distinctly different from those without HIV infection; some of these have an association with the probability of adverse outcome.

OBJETIVOS: Comparar los hallazgos clínicos, radiológicos y del líquido cefalorraquídeo (LCR) entre pacientes adultos con meningitis tuberculosa (MTB) con o sin infección de VIH en su ingreso al hospital, e identificar los factores que predicen la evolución clínica adversa en seis meses. MÉTODOS: Un total de 82 pacientes adultos con MTB fueron incluidos (40 VIH positivos y 42 VIH negativos). Se registraron varios parámetros: clínicos (duración de la enfermedad, puntuación de la Escala de Coma de Glasgow, presencia de alta temperatura, dolor de cabeza, anormalidad del esfínter o nervio craneal, o anormalidad del esfínter, convulsiones y disfunción endocrina); radiológicos (la presencia de hidrocefalia, infarto cerebral, edema, realce meníngeo, granuloma); y del líquido (glucosa, proteína, lactato, linfocitos, neutrófilos, y valores de adenosina deaminasa), junto con un conteo de CD4 en la sangre periférica. Se realizó un análisis estadístico usando la prueba de chi-cuadrado. La variable individual se evaluó como factor pronóstico de la evolución clínica en ambos, calculando el riesgo relativo de asociación para cada uno. RESULTADOS: Una temperatura de más de 38.33ºC fue más común en el grupo VIH negativo, mientras que convulsiones, hidrocefalia, infarto cerebral, y bajo conteo de CD4 ocurrieron significativamente más normalmente en el grupo VIH positivo. La hidrocefalia estuvo fuertemente asociada con un déficit neurológico severo y la convulsión con la muerte en ambos grupos. CONCLUSIÓN: Varias características clínicas y de laboratorio del MTB en pacientes que son VIH positivos, difieren claramente de aquellos con infección por VIH. Algunas de estas características se hallan asociadas con la probabilidad de una evolución clínica adversa.

Paradoxical reaction in tubercular meningitis resulting in involvement of optic radiation.

A 25-year-old woman was diagnosed to have tubercular meningitis (TBM) with a right parietal infarct. She responded well to four-drug anti-tubercular treatment (ATT), systemic steroids and pyridoxine. Steroids were tapered off in one and a half months; she was put on two-drug ATT after two months. Six months after initial diagnosis she presented with sudden, bilateral visual loss. Vision was 3/200 with afferent pupillary defect and un-recordable field in the right eye; vision was 20/60 in the left eye, pupillary reaction was sluggish and the field showed a temporal hemianopia. On reintroduction of systemic corticosteroids vision improved (20/120 in right eye and 20/30 in left eye) within three days; the field defects improved sequentially to a left homonymous hemianopia, then a left homonymous inferior quadrantonopia. A diagnosis of TBM, on treatment, with bilateral optic neuritis, and right optic radiation involvement was made. Since the patient had been off ethambutol for four months, the optic neuritis and optic radiation lesion were attributed to a paradoxical reaction to tubercular allergen, corroborated by prompt recovery in response to corticosteroids. This is the first report of optic radiation involvement in a paradoxical reaction in neuro-tuberculosis in a young adult.

Use of urokinase in the treatment of tuberculous meningitis hydrocephalus

We present a patient with hydrocephalus after tuberculous meningitis successfully treated with urokinase. She presented with multiple episodes of headache, fever, and vomiting. She underwent external ventricular drainage and was treated with urokinase in addition to dexamethasone, acetazolamide, and 4 antituberculous drugs. She was evaluated clinically, radiologically, and by laboratory work-up. On short-term clinical follow-up [3 months], she was asymptomatic after the treatment with urokinase. She was radiologically evaluated 3 weeks after the treatment. An MRI of the brain showed a decrease in ventricular size. Urokinase can be considered as a safe and promising adjunctive treatment for tuberculous meningitis hydrocephalus

Catheter-related candidemia caused by Candida lipolytica in a child with tubercular meningitis.

Candida lipolytica is weakly pathogenic yeast, which is rarely isolated from the blood. We recovered this species from repeated blood samples and in the central venous catheter in a debilitated pediatric patient of tubercular meningitis. Identity was established on the basis of colony morphology and sugar assimilation tests (ID 32C assimilation profile). The fungemia and associated fever subsided after the removal of catheter and amphotericin B therapy. The data suggest that though of low virulence and usually a contaminant, C. lipolytica is emerging yeast pathogen in cases of catheter-related candidemia. Pathogenicity is indicated by isolation from repeated samples as in our case. Intensive therapy is recommended in cases not resolving spontaneously or responding to removal of catheter alone.

Multi drug resistant tuberculous meningitis in pediatric age group

Past decade has seen increase in cases of tuberculous meningitis [TBM] and multidrug resistance in such cases. The mortality rate for a mismanaged TBM is very high which increases manifold in presence of associated complicating factors. The present study was thus planned to evaluate the prevalence of MDR-TBM and look for associated complicating factors and carry out drug sensitivity pattern in all culture positive isolates. One hundred cerebro-spinal fluid [CSF] samples from children clinically suspected of having TBM were collected and processed for detection of Mycobacterium tuberculosis by conventional methods like Ziehl-Neelsen [ZN] staining, Lowenstein- Jensen [LJ] culture and newer method like BACTEC 460 TB culture. Antimicrobial susceptibility was performed on all culture positive isolates by BACTEC 460 TB system. Twenty two cases could be diagnosed as definitive TBM based on BACTEC culture. Of these 22 cases, six cases [27.3%] were positive by ZN staining and/or LJ culture. Of all isolates tested for drug sensitivity 18 were sensitive to all four drugs whereas 4 isolates were resistant to more than one drug. Since the prevalence of MDR-TBM is very high we conclude that all CSF samples should be subjected to sensitivity testing to diagnose it at an early time and determine its sensitivity pattern in view of its very high mortality

Factors associated to the positive cerebrospinal fuid culture in the tuberculous meningitis

Central nervous system involvement is the most common neurological complication in the course of tuberculosis. The lack of rapid and sensitive tests delays the early diagnosis. Here, we retrospectively reviewed the cerebrospinal fluid (CSF) examination of 30 patients with tuberculous meningitis confirmed by bacteriological tests (culture and/or polymerase chain reaction). The purpose of the present study was to determine the CSF parameters associated to the positive CSF culture for Mycobacterium tuberculosis in tuberculous meningitis. We found higher frequency of positive CSF culture in patients infected with HIV as well in patients with high number of neutrophils and high protein content (characteristic in the early or acute-stage patients), which suggests that the positive culture found in these patients may be associated with the presence of high bacillary load in CSF occurring in these stages.

A meningite tuberculosa é a complicação neurológica mais freqüente no curso da tuberculose. Entretanto, a carência de testes rápidos e sensíveis dificulta o diagnóstico precoce, contribuindo para o elevado índice de letalidade desta condição. Na presente análise, é feita revisão dos achados do líquido cefalorraquidiano (LCR) de 30 pacientes com o diagnóstico de meningite tuberculosa confirmado pelo exame bacteriológico. O objetivo do estudo consiste em caracterizar os parâmetros associados à positividade da cultura para Mycobacterium tuberculosis no LCR. Observamos maior freqüência de cultura positiva entre os pacientes infectados pelo HIV e naqueles que apresentam aumento de neutrófilos e da concentração de proteína no LCR. Nossos achados se justificam pelo fato de que na co-infecção com o HIV ocorre maior carga bacilífera em comparação aos pacientes não co-infectados. A presença de neutrofilorraquia e hiperproteinorraquia são marcadores de inflamação aguda, onde se supõe existir também maior concentração de bactérias no LCR.

Infartos cerebrales e hidrocefalia secundaria a meningitis tuberculosa: revisión a partir de un caso clínico / Brain infarcts and hydrocephaly secondary to tuberculosis meningitis: clinic case review

La tuberculosis sigue siendo un importante problema y un tópico de la salud pública de magnitud considerable. La tuberculosis que compromete al sistema nervioso central es un importante y serio compromiso extrapulmonar. El infarto y la hidrocefalia cerebral son complicaciones graves de la meningitis tuberculosa y son de mal pronóstico. Presentamos a un paciente con tuberculosis miliar y compromiso meníngeo que cursa con infartos cerebrales múltiples e hidrocefalia. Él presentó una mala evolución y falleció.

Tuberculosis remains a major global problem and a public health issue of considerable magnitude.Tuberculosis involvement of the central nervous system is an important and serious type of extra pulmonary involvement.Cerebral infarction and hydrocephalus are serious complications of tuberculous meningitis and may worsen the prognosis.We present a patient of milliar tuberculosis and meningeal compromise that course with multiple cerebral infarcts and hydrocephalus. He had a poor outcome.

Cerebral salt wasting syndrome in a patient with tuberculous meningitis.

We report a case of a 65 year male with meningitis who had polyuria, severe hyponatremia, volume depletion and very high urinary sodium excretion. He was diagnosed to have cerebral salt wasting syndrome based on clinical and laboratory parameters.

Tuberculous meningoencephalomyelitis and coinfection with HTLV-I + HTLV-II: case report

Os vírus HTLV-I e HTLV-II são endêmicos em algumas regiões do Brasil, onde uma das doenças associadas, a paraparesia espástica tropical/mielopatia associada ao HTLV (PET/MAH), tem sido diagnosticada em significativo número de pacientes infectados. Nesses indivíduos, a prevalência de tuberculose é maior que na população geral, sugerindo que possa haver um maior risco para esta comorbidade. Relatamos o caso de um homem de 44 anos coinfectado HTLV-I + HTLV-II que desenvolveu meningoencefalomielite por Mycobacterium tuberculosis. O paciente apresentou recuperação clínica parcial, correção da disfunção de barreira hemato-liquórica e negativação no PCR, mediante o tratamento com corticoesteróides e tuberculostáticos.

Meningitis tuberculosa en adultos: análisis de 53 casos / Tuberculous meningitis in adults: review of 53 cases

La meningitis tuberculosa (MTBC) es la forma más grave de tuberculosis extrapulmonar. El amplio espectro del cuadro clínico y su poca especificidad dificultan su diagnóstico precoz, relacionándose directamente con mayor letalidad. El objetivo de este estudio es analizar las características clínicas de los pacientes con diagnóstico de MTBC en el Hospital de Enfermedades Infecciosas Dr. Lucio Córdova, de Santiago, Chile, entre 1995 y 2002. Se estudiaron 53 casos de MTBC en adultos, con una edad mediana de 39 años. Al ingreso 66 por ciento de los pacientes presentaba algún grado de compromiso de conciencia, pero sólo 30 por ciento la tríada sintomática clásica. El LCR mostró aumento de proteínas, glucosa baja y linfocitosis, en la mayoría de los casos. Treinta por ciento de los pacientes presentó co-infección con VIH; la letalidad en este grupo de pacientes fue mayor, 31 vs 17 por ciento del total de la muestra. La MTBC continúa siendo una enfermedad vigente. El diagnóstico de certeza precoz de esta patología no es posible con los métodos actuales, por lo que la sospecha clínica es importante.