NLRP3 Activation Contributes to Memory Impairment in an Experimental Model of Pneumococcal Meningitis.

Bacterial meningitis is considered a life-threatening condition with high mortality rates. In response to the infection, signaling cascades, producing pro-inflammatory mediators trigger an exacerbated host immune response. Another inflammatory pathway occurs through the activation of inflammasomes. Studies highlight the role of the NLR family pyrin domain containing 3 (NLRP3) in central nervous system disorders commonly involved in neuroinflammation. We aimed to investigate the role of NLRP3 and its inhibitor MCC950 on neurochemical, immunological, and behavioral parameters in the early and late stages of experimental pneumococcal meningitis. For this, adult male Wistar rats received an intracisternal injection of Streptococcus pneumoniae or artificial cerebrospinal fluid as a placebo. The animals were divided into control/saline, control/MCC950, meningitis/saline, and meningitis/MCC950. Immediately after the meningitis induction, the animals received 140 ng/kg MCC950 via intracisternal injection. For the acute protocol, 24 h after induction, brain structures were collected to evaluate cytokines, NLRP3, and microglia. In the long-term group, the animals were submitted to open field and recognition of new objects tests at ten days after the meningitis induction. After the behavioral tests, the same markers were evaluated. The animals in the meningitis group at 24 h showed increased levels of cytokines, NLRP3, and IBA-1 expression, and the use of the MCC950 significantly reduced those levels. Although free from infection, ten days after meningitis induction, the animals in the meningitis group had elevated cytokine levels and demonstrated behavioral deficits; however, the single dose of NLRP3 inhibitor rescued the behavior deficits and decreased the brain inflammatory profile.

[Autoimmune chronic meningitis secondary to pneumococcal meningitis. Report of one case]. / Meningitis crónica autoinmune secundaria a meningitis aguda por neumococo. Caso clínico.

Pneumococcal meningitis produces several inflammatory disorders in susceptible subjects. A worsening of meningitis can occur on the fourth day of evolution in relation with the withdrawal of steroids. Other complications include the development of inflammatory signs in the post-acute stage of infection associated with disseminated vasculitis of the cerebral blood vessels and, even later, an autoimmune chronic meningitis. All these inflammatory complications are well controlled with the use of steroids. We report a 53-year-old woman with pneumococcal meningitis that had a good response to treatment with antibiotics and steroids. On the four day, after the steroids were discontinued, she complained of headache, became confused, and had an abnormal cerebrospinal fluid (CSF), report CT angiography showed signs of arteritis. She improved when the steroids were re-started. She was discharged in good condition but after slow tapering of the steroids over a four-month period she had a relapse of all her symptoms and had a gait disturbance. On readmission, she had an inflammatory CSF, there were no signs of infection and the cerebral MRI showed meningeal thickening with ventricular space enlargement. She improved again with steroids and she is now well on high-dose steroids but deteriorates each time the steroids are stopped. She experienced both acute and sub-acute inflammatory responses and finally developed a chronic meningitis responsive, and is dependent on steroids.

Meningitis crónica autoinmune secundaria a meningitis aguda por neumococo: caso clínico / Autoimmune chronic meningitis secondary to pneumococcal meningitis: report of one case

Pneumococcal meningitis produces several inflammatory disorders in susceptible subjects. A worsening of meningitis can occur on the fourth day of evolution in relation with the withdrawal of steroids. Other complications include the development of inflammatory signs in the post-acute stage of infection associated with disseminated vasculitis of the cerebral blood vessels and, even later, an autoimmune chronic meningitis. All these inflammatory complications are well controlled with the use of steroids. We report a 53-year-old woman with pneumococcal meningitis that had a good response to treatment with antibiotics and steroids. On the four day, after the steroids were discontinued, she complained of headache, became confused, and had an abnormal cerebrospinal fluid (CSF), report CT angiography showed signs of arteritis. She improved when the steroids were re-started. She was discharged in good condition but after slow tapering of the steroids over a four-month period she had a relapse of all her symptoms and had a gait disturbance. On readmission, she had an inflammatory CSF, there were no signs of infection and the cerebral MRI showed meningeal thickening with ventricular space enlargement. She improved again with steroids and she is now well on high-dose steroids but deteriorates each time the steroids are stopped. She experienced both acute and sub-acute inflammatory responses and finally developed a chronic meningitis responsive, and is dependent on steroids.

Meningitis and pneumococcal pyomyositis in a child with intramuscular hemangiomas: an autopsy case report.

Pyomyositis is the bacterial infection of skeletal muscle, usually accompanied by abscesses. The main etiologic agent is Staphylococcus aureus. There are rare cases attributed to Streptococcus pneumoniae. This paper presents an autopsy of a four year old child with multiple congenital intramuscular hemangiomas that developed pneumococcal pyomyositis associated with meningitis. The authors propose the hypothesis that patients with hemangiomas, mainly the intramuscular type, may also represent a risk group for pyomyositis. The possibility of respiratory/meningeal co-infection, might also be considered even if the clinical picture is restricted to the muscular system.

[Stroke in paediatric patients with sickle-cell anaemia]. / Ictus en pacientes pediátricos con anemia falciforme.

INTRODUCTION: Sickle-cell anaemia is the severe homozygotic form of drepanocytosis, a genetic disorder that often occurs among black people and which is characterised by the production of haemoglobin S, chronic hemolytic anaemia and tissue ischaemia due to alterations in blood flow. A quarter of the patients presented neurological manifestations; 8-10% of children will have a stroke. AIM. To analyse the cases of stroke in children with sickle-cell anaemia in our centre. PATIENTS AND METHODS: We conducted a retrospective descriptive study of children with sickle-cell anaemia and stroke. RESULTS: Five patients (two Dominicans and three Guineans) with sickle-cell anaemia and stroke; one patient suffered two episodes of stroke. The mean age was 27 months. Five of the episodes were ischaemic infarctions. Stroke was the initial form of presentation of drepanocytosis on three occasions. Two of the strokes occurred within a context of pneumococcal meningitis. Four of the patients had previously reported fever. The initial clinical picture was hemiparesis in four cases. Mean haemoglobin on diagnosing the stroke was 6.5 g/dL. Transcranial ultrasound imaging revealed alterations in three patients and, in all the patients, magnetic resonance imaging revealed lesions, which were bilateral in half the cases. Following the stroke, a hypertransfusion regimen protocol was established and only one patient presented a new stroke. This same patient went on to develop moya-moya disease and was submitted to an indirect revascularisation; the patient progressed well, without presenting any new ischaemic events. CONCLUSIONS: Drepanocytosis is a disease that is emerging in our setting as a result of immigration. It should be suspected in cases of paediatric strokes associated to anaemia, above all in black children under the age of five who were not submitted to neonatal screening.

TITLE: Ictus en pacientes pediatricos con anemia falciforme.Introduccion. La anemia falciforme es la forma homocigota, grave, de drepanocitosis, un trastorno genetico, frecuente en raza negra, caracterizado por la produccion de hemoglobina S, anemia hemolitica cronica e isquemia tisular por alteracion del flujo sanguineo. Una cuarta parte de los pacientes presenta manifestaciones neurologicas; el 8-10% de los niños sufrira un ictus. Objetivo. Analizar los casos de ictus en niños con anemia falciforme en nuestro centro. Pacientes y metodos. Estudio descriptivo retrospectivo de niños con anemia falciforme e ictus. Resultados. Se recogieron cinco pacientes (dos dominicanos y tres guineanos) con anemia falciforme e ictus; un paciente sufrio dos episodios ictales. La edad media fue de 27 meses. Cinco episodios fueron infartos isquemicos. El ictus fue la forma de inicio de la drepanocitosis en tres ocasiones. Dos de los ictus ocurrieron en un contexto de meningitis neumococica. En cuatro pacientes hubo fiebre previa. La clinica inicial fue hemiparesia en cuatro casos. La hemoglobina media al diagnostico de ictus fue de 6,5 g/dL. En tres pacientes se hallaron alteraciones en la ecografia transcraneal y, en todos los pacientes, lesiones en la resonancia magnetica, que en la mitad eran bilaterales. Tras el ictus se inicio un protocolo de regimen hipertransfusional, y solo un paciente presento un nuevo ictus, que desarrollo un sindrome moya-moya y fue sometido a una revascularizacion indirecta, con buena evolucion, sin presentar nuevos eventos isquemicos posteriores. Conclusiones. La drepanocitosis es una enfermedad emergente en nuestro medio debido a la inmigracion. Debe sospecharse en ictus pediatricos asociados a anemia, sobre todo en menores de 5 años de raza negra no sometidos a cribado neonatal.

Displasia de Mondini asociada a meningitis bacteriana recurrente, correlación clínico-imagenológica / Mondini dysplasia associated to recurrent bacterial meningitis-a clinical and imaging correlation

Se describe la displasia de Mondini asociada a pérdida auditiva y meningitis bacteriana recurrente. La malformación de Mondini representa el 30 por ciento de las anomalías congénitas del oído interno, puede ser unilateral o bilateral, y su principal característica consiste en el desarrollo coclear incompleto, causante de grados variables de hipoacusia neurosensorial. Se considera que la ocurrencia de esta malformación se produce por disrupción del desarrollo embrionario durante la séptima semana de gestación, en la cual se detiene el desarrollo coclear. Se presenta el caso de una niña de 12 años, atendida en los Servicios de Pediatría y Otorrinolaringología del Hospital Pediátrico Universitario William Soler, por presentar 3 infecciones meningoencefálicas, en las cuales se aisló Streptococcus pneumoniae serotipo 19F, y se constató hipoacusia neurosensorial severa en el oído izquierdo. La tomografía axial computarizada de alta resolución del oído (cortes axiales y coronales), evidenció la malformación coclear y vestibular, con presencia de tejido en el oído medio que se comunicaba directamente con el oído interno del lado izquierdo a nivel de la ventana oval. Se destaca la importancia de la sospecha clínica de displasia de Mondini, y el impacto científico de la tomografía computarizada del hueso temporal, para el diagnóstico precoz de fístula congénita en el oído interno asociada a meningitis bacteriana recurrente(AU)

Mondini dysplasia associated to hearing loss and recurrent bacterial meningitis was described in this paper. Mondini malformation accounts for 30 percent of congenital anomalies in the inner ear, either unilateral or bilateral, and its main characteristic is the incomplete cochlear development causing various grades of neurosensory hypoacusis. It is considered that the occurrence of this malformation results from the disruption of the embryonal development on the 7th week of gestation when the cochlear development ceases. This is the case of 12 years-old girl who was attended to at the pediatric and otorhinolaryngology service of William Soler" university pediatric hospital because she presented with three meningoencephalic infections from which Streptococcus pneumonia serotype 19F was isolated. It was also confirmed that she suffered severe neurosensory hypoacusis in her left ear. High-resolution computerized axial tomography of the ear (axial and coronal planes) evinced the cochlear and vestibular malformation, with tissue of the middle ear communicating directly with the inner ear of the left size at the oval window. This paper underlined the importance of the clinical suspicion of Mondini disease, and the scientific impact of the computerized axial tomography of the temporal bone in order to early diagnose the congenital fistula in the inner ear associated to recurrent bacterial meningitis(AU)

Displasia de Mondini asociada a meningitis bacteriana recurrente, correlación clínico-imagenológica / Mondini dysplasia associated to recurrent bacterial meningitis-a clinical and imaging correlation

Se describe la displasia de Mondini asociada a pérdida auditiva y meningitis bacteriana recurrente. La malformación de Mondini representa el 30 por ciento de las anomalías congénitas del oído interno, puede ser unilateral o bilateral, y su principal característica consiste en el desarrollo coclear incompleto, causante de grados variables de hipoacusia neurosensorial. Se considera que la ocurrencia de esta malformación se produce por disrupción del desarrollo embrionario durante la séptima semana de gestación, en la cual se detiene el desarrollo coclear. Se presenta el caso de una niña de 12 años, atendida en los Servicios de Pediatría y Otorrinolaringología del Hospital Pediátrico Universitario William Soler, por presentar 3 infecciones meningoencefálicas, en las cuales se aisló Streptococcus pneumoniae serotipo 19F, y se constató hipoacusia neurosensorial severa en el oído izquierdo. La tomografía axial computarizada de alta resolución del oído (cortes axiales y coronales), evidenció la malformación coclear y vestibular, con presencia de tejido en el oído medio que se comunicaba directamente con el oído interno del lado izquierdo a nivel de la ventana oval. Se destaca la importancia de la sospecha clínica de displasia de Mondini, y el impacto científico de la tomografía computarizada del hueso temporal, para el diagnóstico precoz de fístula congénita en el oído interno asociada a meningitis bacteriana recurrente

Mondini dysplasia associated to hearing loss and recurrent bacterial meningitis was described in this paper. Mondini malformation accounts for 30 percent of congenital anomalies in the inner ear, either unilateral or bilateral, and its main characteristic is the incomplete cochlear development causing various grades of neurosensory hypoacusis. It is considered that the occurrence of this malformation results from the disruption of the embryonal development on the 7th week of gestation when the cochlear development ceases. This is the case of 12 years-old girl who was attended to at the pediatric and otorhinolaryngology service of William Soler" university pediatric hospital because she presented with three meningoencephalic infections from which Streptococcus pneumonia serotype 19F was isolated. It was also confirmed that she suffered severe neurosensory hypoacusis in her left ear. High-resolution computerized axial tomography of the ear (axial and coronal planes) evinced the cochlear and vestibular malformation, with tissue of the middle ear communicating directly with the inner ear of the left size at the oval window. This paper underlined the importance of the clinical suspicion of Mondini disease, and the scientific impact of the computerized axial tomography of the temporal bone in order to early diagnose the congenital fistula in the inner ear associated to recurrent bacterial meningitis

Inhibition of matrix metalloproteinases-2 and -9 prevents cognitive impairment induced by pneumococcal meningitis in Wistar rats.

Pneumococcal meningitis is a relevant clinical disease characterized by an intense inflammatory reaction into the subarachnoid and ventricular spaces, leading to blood-brain barrier breakdown, hearing loss, and cognitive impairment. Matrix metalloproteinases (MMPs) are capable of degrading components of the basal laminin, thus contributing to BBB damage and neuronal injury. In the present study, we evaluated the effects of MMP-2, MMP-9, and MMP-2/9 inhibitors on BBB integrity, learning, and memory in Wistar rats subjected to pneumococcal meningitis. The animals underwent a magna cistern tap and received either 10 µL sterile saline as a placebo or an equivalent volume of a Streptococcus pneumoniae suspension at a concentration of 5 × 10(9)cfu/mL. The rats were randomized into different groups that received adjuvant treatment with MMP-2, MMP-9 or MMP-2/9 inhibitors. The BBB integrity was evaluated, and the animals were habituated to open-field and object recognition tasks 10 days after meningitis induction. Adjuvant treatments with inhibitors of MMP-2 or MMP-2/9 prevented BBB breakdown in the hippocampus, and treatments with inhibitors of MMP-2, MMP-9 or MMP-2/9 prevented BBB breakdown in the cortex. Ten days after meningitis induction, the animals that received adjuvant treatment with the inhibitor of MMP-2/9 demonstrated that animals habituated to the open-field task faster and enhanced memory during short-term and long-term retention test sessions in the object recognition task. Further investigation is necessary to provide support for MMP inhibitors as an alternative treatment for bacterial meningitis; however, these findings suggest that the meningitis model could be a good research tool for studying the biological mechanisms involved in the behavioral alterations associated with pneumococcal meningitis.

Factores asociados con la mortalidad por meningitis neumocócica en hospitales de La Habana / Factors associated with mortality due to pneumococcal meningitis in Havana hospitals

Introducción: la meningitis neumocócica constituye un serio problema de salud por su alta morbilidad, letalidad y graves secuelas. Objetivos: identificar algunos factores de riesgo asociados con la mortalidad por meningitis neumocócica. Métodos: se realizó un estudio de caso-control en 7 hospitales de La Habana (enero de 2002-diciembre de 2011) de 45 pacientes (0-86 años de edad), con meningitis neumocócica confirmada: 15 fallecidos (casos) y 30 sobrevivientes (controles), a partir de la vigilancia nacional de síndromes neurológicos bacterianos, historias clínicas, movimientos hospitalarios, tarjetas de enfermedades de declaración obligatoria y registros de laboratorio. Se midió la asociación (análisis bivariado y multivariado) de algunos factores con la muerte a través de la oportunidad relativa y su intervalo de confianza a 95 por ciento, considerando asociación cuando fue mayor o igual que 2. Resultados: la letalidad general resultó de 33,3 por ciento. La media entre el inicio de los síntomas y la consulta médica fue de 2,4 días; entre la consulta y el ingreso 0,5 días; entre el ingreso y el diagnóstico 0,4 días, y entre el diagnóstico y el tratamiento 0,2 días. La estadía hospitalaria media fue de 12,2 días. El análisis bivariado y multivariado mostró asociación significativa de la inconsciencia al ingreso, con la muerte. Otras variables se asociaron con el desenlace fatal pero no fueron significativas. Conclusiones: estar inconsciente al momento del ingreso es un factor de riesgo para la muerte por meningitis neumocócica, en los pacientes con esta enfermedad de los hospitales investigados en La Habana(AU)

Introduction: pneumococcal meningitis is a critical public health problem with a high rate of morbidity and mortality and serious sequelae. Objectives: identify some risk factors associated with mortality due to pneumococcal meningitis. Methods: a case-control study was conducted of 45 patients aged 0-86 with confirmed pneumococcal meningitis cared for in seven Havana hospitals from January 2002 to December 2011. Of the 45 patients studied, 15 had died (cases) and 30 had survived (controls). The study was based on national bacterial neurological syndrome surveillance data, medical records, hospital movements, notifiable disease cards and laboratory records. Association (bivariate and multivariate analysis) of some factors with death was measured through odds ratio with a confidence interval of 95 percent, considering it an association if greater than or equal to 2. Results: overall case-fatality rate was 33.3 percent. Mean time between the onset of symptoms and medical consultation was 2.4 days; between consultation and admission 0.5 day; between admission and diagnosis 0.4 day; and between diagnosis and treatment 0.2 day. Mean hospital stay was 12.2 days. Bivariate and multivariate analysis revealed a significant association between unconsciousness at admission and death. Other variables were associated with death as well, but they were not significant. Conclusions: being unconscious at admission is a risk factor for death due to pneumococcal meningitis in patients with this disease in the Havana hospitals studied(AU)

Attenuation of cognitive impairment by the nonbacteriolytic antibiotic daptomycin in Wistar rats submitted to pneumococcal meningitis.

BACKGROUND: Streptococcus pneumoniae is associated with neurologic sequels, such as, seizures, sensory-motor deficits, hearing loss, learning and memory impairment, which can occur in approximately 30 to 52% of surviving patients. Neuronal damage can be caused by intense inflammatory reaction and direct effects of the bacteria virulence factors. The aim of the present study was to evaluate the effects of the nonbacteriolytic antibiotic daptomycin versus ceftriaxone on behavioral parameters in adult Wistar rats submitted to pneumococcal meningitis. RESULTS: Ten days after induction we verified that the meningitis group with daptomycin treatment showed retention of aversive memory; it presented memory of the object recognition at short term and long term. In continuous multiple-trials step-down inhibitory avoidance task the meningitis group with ceftriaxone treatment required approximately two times more stimulus to reach the acquisition criterion when compared with meningitis group with daptomycin treatment. However, in the habituation memory test there were no differences in the number of crossings and rearings in training and task sessions demonstrating habituation impairment to the environment task in both meningitis groups. CONCLUSIONS: The evidence of the present study shows the potential alternative of the treatment with daptomycin in preventing learning and memory impairments caused by pneumococcal meningitis. Further investigations are necessary to provide support for evaluation of daptomycin as an alternative treatment of bacterial meningitis.

Caracterização molecular de sorotipos não-vacinais de Streptococcus pneumoniae isolados de pacientes com meningite em Salvador, antes e após a implementação da vacina conjugada PCV-10 / Molecular characterization of non-vaccine serotypes of Streptococcus pneumoniae isolates from meningitis patients in Salvador, before and after implementation of the conjugate vaccine PCV-10

O advento das vacinas pneumocócicas conjugadas veio contribuir de forma decisiva para a redução da incidência dos casos de doença invasiva por S. pneumoniae em vários países do mundo. Em contrapartida, tem-se verificado um aumento de casos decorrentes de sorotipos não vacinais, que escapam da vacina e reduzem o seu efeito a partir da expansão de clones pré-existentes com consequente substituição de sorotipos e/ou do fenômeno de troca capsular (capsular switching). No Brasil, a vacina conjugada 10-valente (PCV10) foi introduzida no calendário nacional de imunização a partir de 2010. Este estudo teve como objetivo caracterizar através de técnicas fenotípicas e moleculares os sorotipos não-vacinais (SNVT) de S.pneumoniae, isolados de pacientes com meningite nos períodos anterior (janeiro/2008 - junho/2010) e posterior (julho/2010 - dezembro/2012) à implementação da vacina pneumocócica conjugada 10-valente (PCV10), na cidade de Salvador, Bahia. Os isolados de S. pneumoniae foram identificados através de métodos microbiológicos clássicos e a determinação do tipo capsular foi realizada através da técnica de Multiplex-PCR e/ou reação de Quellung. A sensibilidade a oito antimicrobianos foi realizada através da técnica de microdiluição em caldo e a caracterização genotípica por intermédio das técnicas de PFGE e MLST...

The licensure and subsequent widespread use of pneumococcal conjugate vaccines have contributed for the reduction in the overall incidence of invasive pneumococcal disease worldwide. However, the emergence of Streptococcus pneumoniae nonvaccine serotypes (SNVT), which escape from the vaccine by the expansion of pre-existing clones following serotype replacement and/or by capsular switching is a matter of concern. In 2010, Brazil introduced the 10-valent conjugate pneumococcal vaccine (PCV10) into its routine National Immunization Program. Our aim was to characterize the phenotypic and genotypic profile of S. pneumoniae non-vacine serotypes (SNVT) isolated from patients with meningitis before (January 2008 – June 2010) and after (July 2010 – December 2012) the introduction of PCV10 in Salvador, Bahia. The pneumococcal isolates were identified by classical microbiological methods and submitted to capsular deduction by multiplex-PCR and/or Quellung reaction. The antimicrobial susceptibility was performed the broth microdilution method. The genotypic profile was assessed by PFGE and MLST...

Imipramine reverses depressive-like parameters in pneumococcal meningitis survivor rats.

Pneumococcal meningitis is a severe infectious disease of the central nervous system, associated with acute inflammation and might cause damage to the host, such as deafness, blindness, seizure, and learning deficits. However, infectious diseases can play a significant role in the etiology of neuropsychiatric disturbances. In this context, we evaluated depressive-like parameters; corticosterone and ACTH levels in pneumococcal meningitis surviving rats. Wistar rats underwent a magna cistern tap receiving either 10 µL sterile saline or a Streptococcus pneumoniae suspension at the concentration of 5 × 10(9) cfu/mL. After 3 days of meningitis induction procedure, the animals were treated with imipramine at 10 mg/kg or saline for 14 days (3rd-17th day). The consumption of sweet food was measured for 7 days (10th-17th day). The meningitis group decreased the sucrose intake and increased the levels of corticosterone and ACTH levels in the serum and TNF-α in the cortex; however, the treatment with imipramine reverted the reduction of sweet food consumption, normalized hormonal levels and TNF-α in the cortex. Our results supported the hypothesis that the pneumococcal meningitis surviving rats showed depressive-like behavior and alterations in the hypothalamus-pituitary-adrenal axis.

Childhood acute bacterial meningitis: risk factors for acute neurological complications and neurological sequelae.

OBJECTIVE: To assess acute neurological complications and neurological sequelae of childhood acute bacterial meningitis in order to determine possible warning signs. METHODS: This retrospective study evaluated children with acute bacterial meningitis (between 1 month and 14 years of age) admitted between 2003 and 2006. RESULTS: Of the 44 patients studied, 17 (38.6%) had acute neurological complications. Seizure was the most frequent (31.8%) complication. Patients with acute neurological complications showed a higher frequency of lower neutrophil count (p = 0.03), seizure at admission (p < 0.01), and S. pneumoniae as the etiologic agent (p = 0.01). Risk factors for the development of acute neurological complications were S. pneumoniae (odds ratio [OR] = 6.4, confidence interval [CI] 1.7-24.7) and neutrophil count < 60% (p < 0.01). Of the 35 patients who were followed up, 14 had neurological sequelae (40%). Behavioral change (22.9%) was the most frequent sequela. Seizures at admission (OR = 5.6, CI 1.2-25.9), cerebrospinal fluid protein concentration > 200 mg/dL (p < 0.01), and cerebrospinal fluid glucose concentration/glycemia ratio (p < 0.01) were identified as risk variables for sequelae. CONCLUSION: Neutrophil count < 60%, seizure at admission, and S. pneumoniae as the etiologic agent were identified as warning signs for acute neurological complications, while protein levels, cerebrospinal fluid glucose concentration/glycemia ratio, and seizure at admission were seen as risk factors for neurological sequelae.

Dexamethasone treatment reverses cognitive impairment but increases brain oxidative stress in rats submitted to pneumococcal meningitis.

Pneumococcal meningitis is associated with a significant mortality rate and neurologic sequelae. The animals received either 10 µL of saline or a S. pneumoniae suspension and were randomized into different groups: sham: placebo with dexamethasone 0.7 mg/kg/1 day; placebo with dexamethasone 0.2 mg/kg/7 days; meningitis groups: dexamethasone 0.7 mg/kg/1 day and dexamethasone 0.2 mg/kg/7 days. Ten days after induction we evaluated memory and oxidative stress parameters in hippocampus and cortex. In the step-down inhibitory avoidance task, we observed memory impairment in the meningitis group with dexamethasone 0.2 mg/kg/7 days. The lipid peroxidation was increased in hippocampus in the meningitis groups with dexamethasone and in cortex only in the meningitis group with dexamethasone 0.2 mg/kg/7 days. The protein carbonyl was increased in hippocampus in the meningitis groups with dexamethasone and in cortex in the meningitis groups with and without dexamethasone. There was a decrease in the proteins integrity in hippocampus in all groups receiving treatment with dexamethasone and in cortex in all groups with dexamethasone (0.7 mg/kg/1 day). The mitochondrial superoxide was increased in the hippocampus and cortex in the meningitis group with dexamethasone 0.2 mg/kg/7 days. Our findings demonstrate that dexamethasone reverted cognitive impairment but increased brain oxidative stress in hippocampus and cortex in Wistar rats ten days after pneumococcal meningitis induction.

Meningite bacteriana aguda na infância: fatores de risco para complicações agudas e sequelas / Childhood acute bacterial meningitis: risk factors for acute neurological complications and neurological sequelae

OBJETIVO: Estudo retrospectivo que visa avaliar as complicações neurológicas agudas e sequelas neurológicas das meningites bacterianas agudas na infância, a fim de determinar possíveis sinais de alerta. MÉTODOS: Foram avaliadas crianças (entre 1 mês e 14 anos) internadas entre 2003 e 2006, com meningite bacteriana aguda. RESULTADOS: Dos 44 pacientes incluídos, 17 (38,6%) apresentaram complicações neurológicas agudas, sendo crise convulsiva a mais frequente (31,8%). Os pacientes com complicações neurológicas agudas apresentaram com mais frequência: menor contagem de neutrófilos (p = 0,03), crise convulsiva na admissão (p < 0,01) e S. pneumoniae como agente etiológico (p = 0,01). Os fatores de risco para o desenvolvimento de complicações neurológicas agudas foram: S. pneumoniae [razão de chances (odds ratio, OR) = 6,4; intervalo de confiança (IC) 1,7-24,7] e contagem de neutrófilos < 60% (p < 0,01). De 35 pacientes seguidos ambulatorialmente, 14 apresentaram sequelas neurológicas (40%), sendo alteração comportamental a mais frequente. A ocorrência de crise convulsiva na internação (OR = 5,6; IC 1.2-25,9), proteinorraquia > 200 mg/dL (p < 0,01) e menor relação glicorraquia/glicemia (p < 0,01) foram identificadas como variáveis de risco para sequelas. CONCLUSÃO: Contagem de neutrófilos < 60%, crise convulsiva na admissão e S. pneumoniae como agente etiológico foram identificados como sinais de alerta para a ocorrência de complicação neurológica aguda, enquanto que proteinorraquia, menor relação glicorraquia/glicemia e crise convulsiva na internação foram observados como fatores de risco para a ocorrência de sequelas neurológicas.

OBJECTIVE: To assess acute neurological complications and neurological sequelae of childhood acute bacterial meningitis in order to determine possible warning signs. METHODS: This retrospective study evaluated children with acute bacterial meningitis (between 1 month and 14 years of age) admitted between 2003 and 2006. RESULTS: Of the 44 patients studied, 17 (38.6%) had acute neurological complications. Seizure was the most frequent (31.8%) complication. Patients with acute neurological complications showed a higher frequency of lower neutrophil count (p = 0.03), seizure at admission (p < 0.01), and S. pneumoniae as the etiologic agent (p = 0.01). Risk factors for the development of acute neurological complications were S. pneumoniae (odds ratio [OR] = 6.4, confidence interval [CI] 1.7-24.7) and neutrophil count < 60% (p < 0.01). Of the 35 patients who were followed up, 14 had neurological sequelae (40%). Behavioral change (22.9%) was the most frequent sequela. Seizures at admission (OR = 5.6, CI 1.2-25.9), cerebrospinal fluid protein concentration > 200 mg/dL (p < 0.01), and cerebrospinal fluid glucose concentration/glycemia ratio (p < 0.01) were identified as risk variables for sequelae. CONCLUSION: Neutrophil count < 60%, seizure at admission, and S. pneumoniae as the etiologic agent were identified as warning signs for acute neurological complications, while protein levels, cerebrospinal fluid glucose concentration/glycemia ratio, and seizure at admission were seen as risk factors for neurological sequelae.

Depressive-like-behavior and proinflamatory interleukine levels in the brain of rats submitted to pneumococcal meningitis.

Bacterial meningitis due to Streptococcus pneumoniae is associated with a significant mortality rate and persisting neurologic sequelae including sensorymotor deficits, seizures, and impairments of learning and memory. The presence of proliferating bacteria within the subarachnoid and ventricular space compartments triggers an intense inflammatory host response. Proinflammatory mediators released in the process include tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, and all of which have been shown to contribute to the development of brain injury in bacterial meningitis. The animals underwent a magna cistern tap receiving either 10muL sterile saline as a placebo or an equivalent volume of a S. pneumoniae suspension at the concentration 5x10(9)cfu/mL. Ten days after induction we evaluated depressive-like behavior by using the forced swimming test and verified the levels of the TNF-alpha, IL-1beta, IL-6 and CINC-1 in the brain of rats induced to pneumococcal meningitis. In the forced swimming test we observed a significant increase in the immobility time in the meningitis group compared to the sham group (p<0.05). The TNFlevels were found increased in the prefrontal cortex (p<0.05, F=4.921), but not hippocampus. The IL-6, CINC-1 and IL-1beta levels presented no alteration in both prefrontal cortex and hippocampus 10 days after meningitis induction by S. pneumoniae. These findings suggest that the meningitis model could be a good research tool for the study of the biological mechanisms involved in the behavioral alterations secondary to pneumococcal meningitis.

Severe retinal hemorrhages in infants with aggressive, fatal Streptococcus pneumoniae meningitis.

Retinal hemorrhages in children occasionally accompany bacterial meningitis, usually due to hemophilus or meningococcal organisms. The hemorrhages may be intraretinal, usually in the posterior pole of the eye and few in number, or, more uncommonly, subhyaloid or vitreous. Pathogenesis may include vasculitis, disseminated intravascular coagulation, or intracranial hypertension. We report 2 cases of bilateral severe retinal hemorrhages in fatal Streptococcus pneumoniae meningitis.