Experiencia con el Biofire FilmArray® para meningitis/encefalitis infecciosa en una institución de alta complejidad en Bogotá, Colombia / Experience with the Biofire FilmArray® for infectious meningitis/encephalitis in a high complexity institution in Bogotá, Colombia

Introducción: La meningoencefalitis infecciosa (MEI) es una emergencia neurológica con importante morbimortalidad. El panel Biofire FilmArray? para meningitis/encefalitis (FAME) en el líquido cefalorraquídeo (LCR) ha demostrado ser una valiosa herramienta para el diagnóstico etiológico de la MEI, facilitando una terapia antimicrobiana dirigida. El objetivo es determinar el impacto del panel FAME en las decisiones terapéuticas antimicrobianas en pacientes con sospecha de MEI en las primeras 24 horas de la valoración clínica. Pacientes y métodos: Estudio observacional descriptivo que comenta las manifestaciones cínicas, los resultados de neuroimágenes y paraclínicos, y la antibioticoterapia de pacientes con sospecha de MEI. Se realizó un análisis del impacto que tiene el FAME en la terapia antimicrobiana en las primeras 24 horas de la valoración clínica de los pacientes. Resultados: Se incluyó a 44 pacientes. El tiempo promedio para obtener el resultado del panel FAME en el LCR fue de nueve horas, con un 20,4% (9/44) de pruebas positivas. En las primeras 24 horas de la valoración clínica, su resultado tuvo impacto en las decisiones terapéuticas antimicrobianas en el 75% (33/44) de los casos. En pacientes con alta sospecha clínica de MEI, el resultado del FAME permitió cambiar la terapia empírica inicial a una dirigida en el 15% (3/20) y suspender la terapia empírica inicial en el 35% (7/20) de los sujetos. En pacientes con baja sospecha clínica de MEI, su resultado permitió que al 25% (6/24) se le confirmara la sospecha y se le iniciara antibioticoterapia dirigida; y que al 70,8% (17/24) se le descartara el diagnóstico y no se le iniciara tratamiento. Conclusiones: El resultado del panel FAME en el LCR tiene alto impacto en la toma de decisiones terapéuticas antimicrobianas en las primeras 24 horas de la valoración clínica. Sin embargo, su interpretación debe hacerse con el contexto clínico, la epidemiología local y otros estudios diagnósticos.(AU)

Introduction: Infectious meningoencephalitis (IME) is a neurological emergency with a significant rate of morbidity and mortality. The Biofire FilmArray® meningitis/encephalitis (FAME) panel for testing in cerebrospinal fluid (CSF) has proven to be a valuable tool for the aetiological diagnosis of IME, facilitating targeted antimicrobial therapy. The aim is to determine the impact of the FAME panel on antimicrobial therapeutic decisions in patients with suspected IME in the first 24 hours of clinical assessment. Patients and methods: This is a descriptive observational study that comments on the clinical manifestations, the neuroimaging and paraclinical findings, and the antibiotic therapy of patients with suspected IME. An analysis was performed to determine the impact of FAME on antimicrobial therapy in the first 24 hours of the clinical assessment of patients. Results: Altogether 44 patients were included. The average time required to obtain the result of the FAME panel for testing in CSF was nine hours, with 20.4% (9/44) of tests yielding positive results. Within 24 hours of clinical assessment, their outcome had an impact on antimicrobial treatment decisions in 75% (33/44) of cases. In patients with a high clinical suspicion of IME, the result of FAME made it possible to change the initial empirical therapy to a targeted therapy in 15% (3/20) of cases and to discontinue the initial empirical therapy in 35% (7/20) of the subjects. In patients with low clinical suspicion of IME, their result allowed 25% (6/24) to have their suspicion confirmed and they were started on targeted antibiotic therapy; in contrast, 70.8% (17/24) had their diagnosis ruled out and were not started on treatment. Conclusions: The result of the FAME panel for testing in CSF has a high impact on antimicrobial therapeutic decisions within 24 hours of clinical assessment. However, it must be interpreted with the clinical context, local epidemiology and other diagnostic studies.(AU)

Recurrent Meningitis in Congenital Inner Ear Malformation.

Spontaneous cerebrospinal fluid otorrhea is very rare. Because of nonspecific symptoms, it is usually diagnosed when complications such as meningitis occur. Cerebrospinal fluid leak may be caused by cochlea malformation, which permits nonphysiological communication between subarachnoid space and tympanomastoid cavity. Nearly 20% of congenital sensorineural hearing loss is connected with inner ear bone malformation. We present a case of 40-year-old man suffering since early childhood from recurrent meningitis and right ear deafness, caused by congenital internal ear malformation. For many years, patient with sensorineural hearing loss had not undergone diagnostic radiology; computed tomography scans of the temporal bone had not been performed. Developing meningitis in early childhood was regarded as the reason for deafness.

Pitfalls in the diagnosis of meningitis in neonates and young infants: the role of lumbar puncture.

Meningitis occurs frequently in neonates and can lead to a number of acute, severe complications and long-term disabilities. An early diagnosis of neonatal meningitis is essential to reduce mortality and to improve outcomes. Initial clinical signs of meningitis are often subtle and frequently overlap with those of sepsis, and current haematologic tests do not distinguish sepsis from meningitis. Thus, lumbar puncture (LP) remains the gold standard for the diagnosis of meningitis in infants, and this procedure is recommended in clinical guidelines. Nevertheless, in clinical practice, LP is frequently deferred or omitted due to concerns regarding hypothetical adverse events or limited experience of the performer. Future studies should assess whether a combination of clinical findings and select haematologic tests at disease onset can identify those neonates with the highest risk of meningitis who should undergo LP. Furthermore, clinicians should be convinced that the actual benefits of an early diagnosis of meningitis far outweigh the hypothetical risks associated with LP.

Endoscopic cyst fenestration in the treatment of multiloculated hydrocephalus in children.

OBJECTIVES: The treatment of multiloculated hydrocephalus is a difficult problem in pediatric neurosurgery. Definitive treatment is surgical, yet the approach remains controversial. The author has therefore reviewed his results with endoscopic cyst fenestration (ECF) in the management of this disease. METHODS: The author presents the largest series to date of 24 patients with multiloculated hydrocephalus who were treated endoscopically. The group included 10 boys and 14 girls with a mean age of 12.5 months. Uniloculated hydrocephalus was not included in this study because it is a different entity that would be better studied separately. RESULTS: Neonatal meningitis was the most common cause (in 9 patients), followed by intraventricular hemorrhage (in 6 patients), postoperative gliosis (in 6 patients), and multiple neuroepithelial cysts (in 3 patients). Multiplanar magnetic resonance images made early diagnosis possible and are indicated if the computed tomography scan shows disproportionate hydrocephalus. Surgical treatment included ECF (in 24 patients), endoscopic revision of a malfunctioning preexisting shunt (in 6 patients), placement of a new shunt (in 15 patients), and third ventriculostomy (in 3 patients). The ECF was easily performed in all cases through devascularization of the cyst wall by coagulation to prevent recurrence. The results are encouraging with improvement of hydrocephalus in 18 patients (75%). The need for shunt insertion was avoided in 3 patients (12.5%). Endoscopy reduced shunt revision rate from 2.9 per year before fenestration to 0.2 per year after fenestration. During the overall mean follow-up period (30 months), repeated ECF was necessary in 8 patients (33%). Six (75%) of these 8 patients had already undergone shunt treatment before endoscopy. Endoscopic complications were minimal (2 cerebrospinal fluid leaks and 2 minor arterial hemorrhages), and there were no deaths (0%). CONCLUSIONS: An ECF procedure is recommended in the treatment of multiloculated hydrocephalus because it is effective, simple, minimally invasive, and associated with low morbidity and mortality rates.

Chronic infantile neurological cutaneous and articular syndrome is caused by mutations in CIAS1, a gene highly expressed in polymorphonuclear cells and chondrocytes.

Chronic infantile neurological cutaneous and articular (CINCA) syndrome is a severe chronic inflammatory disease of early onset, characterized by cutaneous symptoms, central-nervous-system involvement, and arthropathy. In the present study, we report, in seven unrelated patients with CINCA syndrome, distinct missense mutations within the nucleotide-binding site of CIAS1, a gene encoding cryopyrin and previously shown to cause Muckle-Wells syndrome and familial cold urticaria. Because of the severe cartilage overgrowth observed in some patients with CINCA syndrome and the implications of polymorphonuclear cell infiltration in the cutaneous and neurological manifestations of this syndrome, the tissue-specific expression of CIAS1 was evaluated. A high level of expression of CIAS1 was found to be restricted to polymorphonuclear cells and chondrocytes. These findings demonstrate that CIAS1 missense mutations can result in distinct phenotypes with only a few overlapping symptoms and suggest that this gene may function as a potential inducer of apoptosis.

Central nervous system infections in the pediatric population.

Central nervous system infections and sequelae in the pediatric population may present differently depending on the patient's stage of development. Infections contracted from conception through the neonatal period may affect central nervous system formation, whereas infections acquired later tend to cause parenchymal destruction. This article discusses congenital, focal parenchymal, extra-axial, and diffuse parenchymal infections and their effect on the developing brain.

Identification of regions of the Escherichia coli chromosome specific for neonatal meningitis-associated strains.

Specific virulence factors associated with the pathogenesis of Escherichia coli strains causing neonatal meningitis (ECNM), such as the K1 capsular polysaccharide, the S fimbriae, and the Ibe10 protein, have been previously identified. However, some other yet unidentified factors are likely to be involved in the pathogenesis of ECNM. To identify specialized unique DNA regions associated with ECNM virulence, we used the representational difference analysis technique. The genomes of two strains belonging to nonpathogenic phylogenetic group A of the ECOR reference collection were subtracted from E. coli strain C5, isolated from a case of neonatal meningitis. Strain C5 belongs to the phylogenetic group B2 as do the majority of ECNM. We have isolated and mapped 64 DNA fragments which are specific for strain C5 and not found in nonpathogenic strains. Of these clones, 44 were clustered in six distinct regions on the chromosome. The sfa and ibe10 genes were located in regions 2 and 6, respectively. A group of genes (cnf1, hra, hly, and prs) known to be present in a pathogenicity island of the uropathogenic strain E. coli J96 colocalized with region 6. The occurrence of these DNA regions was tested in a set of meningitis-associated strains and in a control group composed of non-meningitis-associated strains belonging to the same B2 group. Regions 1, 3, and 4 were present in 91, 82, and 81%, respectively, of the meningitis strains and in 40, 13, and 47% of the control strains. Together, these data suggest that regions 1, 3, and 4 code for factors associated with the ability of E. coli to invade the meninges of neonates.

[Acute bacterial and fungal neonatal meningitis]. / Méningites néonatales aiguës bactériennes et fongiques.

Neonatal meningitis has two closely related features: the mechanism of infection and the nature of the pathogen. When transmitted from mother to foetus, the infection is mainly caused by one of three microorganisms: Streptococcus group B, Escherichia coli or Listeria monocytogenes. It may occur before birth, in which case meningitis is of early onset and has a rather poor prognosis. When it occurs later, the infection is a pathological consequence of physiological bacterial colonization, and its symptoms and prognosis are those of post-natal meningitis. Post-natal infections are facilitated by a pre-existing pathology or by prematurity. The responsible organisms (Gram-positive or Gram-negative bacteria, or yeasts) are often multiresistant. Advances in biology provide increasingly clearer explanation of the cerebral complications that determine the medium- and long-term prognosis. The variety of organisms and their frequent resistance to antibacterials make it necessary to use antibiotics that possess an exceptionally broad spectrum.

[Congenital syphilitic meningomyelitis manifested in the adult]. / Méningo-myélite syphilitique congénitale révélée à l'âge adulte.

We report a case of neurosyphilis of the spinal cord in a 38-year-old-man presenting with urinary incontinence and Argyll-Robertson sign. Anamnesis revealed the congenital origin of the disease. Urodynamics findings were consistent with a conus medullaris involvement and CSF study revealed a specific lymphocytic meningitis. A specific spinal arteritis was found by angiography. A quarterly 15 to 20 days course of intravenous penicillin was then instituted during 2 years. A specific treatment of urinary symptoms resulted in complete disappearance of sphincter dyssynergia. Antibiotic therapy was followed by clinical improvement and regression of most of the CSF abnormalities.

Tabicamiento ventricualr en hidrocefalia / Ventricular septations in hydrocephalus

La formación del septum o tabiques en los ventriculos cerebrales suele presentarse en las meningoventriculitis tanto atriales como peritoneales. Se presentan 6 casos con estudios de tomografía computarizada (T.C.)

Infection of the fetus and the newborn: prevention, treatment and related handicap.

Congenital infection is uncommon and the cause of only a small proportion of handicap seen in children but some infections may be preventable or even treatable. As an example, the congenital rubella syndrome first described in the 1940s is preventable by use of the vaccine but cases still occur. It is hoped that with the introduction of the measles, mumps, rubella immunization for young children, rubella will become as rare in the UK as it is in the USA. Cytomegalovirus is now a more common cause of handicap than rubella but no vaccine has been developed. Although antiviral drugs are available for herpes simplex virus and vaccinia, infection mortality in the newborn is high, even following the use of these agents; many HSV infections in the newborn arise following primary and asymptomatic maternal infections so that treatment may start late in the course of the illness. The obstetrician needs to understand the natural history as well as possible investigations available for congenital infections. There may be warning signs which require action, such as herpetic lesions in the genital tract of the mother. Less specific abnormalities during pregnancy, such as intra-uterine growth retardation and spontaneous onset of preterm labour, may point to congenital infection. This chapter describes both antenatal and postnatal management of the major congenital infections. We have included recent research data that should influence clinical practice; studies on HSV which suggest that, for women with a history of recurrent infection, routine viral culture of the genital tract at the end of pregnancy is unnecessary; reports from both the USA and the UK that rubella immunization performed inadvertently during early pregnancy has not resulted in the congenital rubella syndrome. The chapter would not have been complete without a discussion of human immunodeficiency virus, of concern to the obstetrician and midwife. There is still much to be learned about the natural history of this infection in both the mother and infant.

Neuroradiological findings in multiloculated hydrocephalus.

The characteristic neuroradiological features of multiloculated hydrocephalus following neonatal meningitis and ventriculitis in five infants are presented. The role of ventriculography and computerized tomography in detecting multiloculated and enlarged ventricles and paraventricular cavities, as well as complete and incomplete septa, is emphasized for early diagnosis and surgical management. CT scan also provides clues indicating the presence of thin but not visualized septa. It is suggested that post-meningitic hydrocephalus should be repeatedly followed-up for detection of multiloculated transformation. Probably this entity occurs less uncommonly than was thought in the past. The CT scan appears the most helpful and safe procedure for the serial evaluation, but ventriculography may be usefully combined with it in order to plan the most suitable operative approach for fenestration of membranes.