RESUMEN
RATIONALE: Group B Streptococcus (GBS) remains a principal pathogen causing neonatal sepsis and meningitis, particularly in premature infants with relatively insufficient immunity. Recurrence may occur uncommonly, largely associated with subclinical mucosal persistence or repetitive exposure to exogenous sources. White matter injury (WMI) including cystic periventricular leukomalacia (PVL) has been associated with intrauterine infection/inflammation, and neonatal infection as a more significant predictor including postnatal sepsis and recurrent infection, even without microbial neuroinvasion. Furthermore, clinical and experimental evidence of WMI by some bacteria other than GBS without central nervous system invasion has been reported. However, there is little evidence of WMI associated with neonatal GBS sepsis in the absence of meningitis in the literature. PATIENT CONCERNS: A newborn at 30+4 weeks' gestation with low birthweight presented with 2 episodes (with a 13-day interval with no antibiotic therapy) of neonatal sepsis culture-proven for GBS with early-onset presentation after clinical chorioamnionitis via vertical GBS transmission and the associated conditions including prematurity-related neonatal immunodeficiency and persistent mucosal GBS carriage after the first antibiotic treatment. The perinatal GBS infection was complicated by progressive WMI presenting with ventriculomegaly and cystic PVL without a definite evidence of meningitis, intraventricular hemorrhage, and documented cerebral hypoxia or hypoperfusion conditions including septic shock. DIAGNOSES: Recurrent group B streptococcal sepsis and cystic PVL with ventriculomegaly. INTERVENTIONS: Two episodes of GBS sepsis were treated with 15-day parenteral antibiotic therapy, respectively. OUTCOMES: Resolution of the recurrent GBS sepsis without further relapses, however, complicated by WMI and subsequent about 6âmonths delay in motor development at 12 months' corrected age. LESSONS: This case suggests WMI associated with GBS bacteremia without central nervous system entry by viable GBS and also shows that in premature infants, intrauterine GBS infection with no interventions may lead to extensive and persistent GBS colonization, early-onset and recurrent GBS disease, and WMI. Postnatal as well as intrauterine infection/inflammation controls with maternal prophylaxis may be pivotal for prevention and limiting the magnitude of neurologic injury.
Asunto(s)
Leucomalacia Periventricular/microbiología , Sepsis Neonatal/microbiología , Complicaciones Infecciosas del Embarazo/microbiología , Infecciones Estreptocócicas/complicaciones , Streptococcus agalactiae/aislamiento & purificación , Administración Intravenosa , Antibacterianos/administración & dosificación , Corioamnionitis/diagnóstico , Corioamnionitis/microbiología , Discapacidades del Desarrollo/diagnóstico , Discapacidades del Desarrollo/microbiología , Quimioterapia Combinada/métodos , Femenino , Humanos , Hidrocefalia/diagnóstico , Hidrocefalia/microbiología , Lactante , Recién Nacido de Bajo Peso , Recién Nacido , Recien Nacido Prematuro , Transmisión Vertical de Enfermedad Infecciosa , Leucomalacia Periventricular/diagnóstico , Leucomalacia Periventricular/patología , Imagen por Resonancia Magnética , Masculino , Edad Materna , Sepsis Neonatal/diagnóstico , Sepsis Neonatal/terapia , Embarazo , Complicaciones Infecciosas del Embarazo/diagnóstico , Recurrencia , Infecciones Estreptocócicas/diagnóstico , Infecciones Estreptocócicas/microbiología , Infecciones Estreptocócicas/transmisión , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/microbiología , Sustancia Blanca/patología , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: Magnetic resonance imaging (MRI) of the brain in scrub typhus meningoencephalitis is non-specific, and in the majority of the cases, conventional MRI fails to detect any abnormality. However, autopsy reports depict central nervous system involvement in almost all patients. There is therefore a need for research on the quantitative assessment of brain parenchyma that can detect microstructural abnormalities. The study aimed to assess the microstructural integrity changes of scrub typhus meningoencephalitis by using different diffusion tensor imaging (DTI) parameters. METHODS: This was a retrospective analysis of scrub typhus meningoencephalitis. Seven patients and seven age- and sex-matched healthy controls were included. Different DTI parameters such as apparent diffusion coefficient (ADC), fractional anisotropy (FA), relative anisotropy (RA), trace, volume ratio (VR) and geodesic anisotropy (GA) were obtained from six different regions of subcortical white matter at the level of the centrum semiovale. Intergroup significant difference was determined by one-way analysis of variance followed by Tukey's post hoc test. Receiver operating characteristic curves were constructed to determine the accuracy of the DTI matrices. RESULTS: There was a significant decrease in FA, RA and GA as well as an increase in ADC and VR in the subcortical white matter in patients with scrub typhus meningoencephalitis compared to controls (p < 0.001). The maximum sensitivity of the DTI parameters was 85.7%, and the maximum specificity was 81%. CONCLUSION: There was an alteration of subcortical white-matter integrity in scrub typhus meningoencephalitis that represents the axonal degeneration, myelin breakdown and neuronal degeneration. DTI may be a useful tool to detect white-matter abnormalities in scrub typhus meningoencephalitis in clinical practice, particularly in patients with negative conventional MRI.
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Imagen de Difusión Tensora/métodos , Meningoencefalitis/diagnóstico por imagen , Meningoencefalitis/microbiología , Tifus por Ácaros/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/microbiología , Adulto , Anisotropía , Femenino , Humanos , Masculino , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
Structural and molecular myelination deficits represent early pathological features of Huntington disease (HD). Recent evidence from germ-free (GF) animals suggests a role for microbiota-gut-brain bidirectional communication in the regulation of myelination. In this study, we aimed to investigate the impact of microbiota on myelin plasticity and oligodendroglial population dynamics in the mixed-sex BACHD mouse model of HD. Ultrastructural analysis of myelin in the corpus callosum revealed alterations of myelin thickness in BACHD GF compared to specific-pathogen free (SPF) mice, whereas no differences were observed between wild-type (WT) groups. In contrast, myelin compaction was altered in all groups when compared to WT SPF animals. Levels of myelin-related proteins were generally reduced, and the number of mature oligodendrocytes was decreased in the prefrontal cortex under GF compared to SPF conditions, regardless of genotype. Minor differences in commensal bacteria at the family and genera levels were found in the gut microbiota of BACHD and WT animals housed in standard living conditions. Our findings indicate complex effects of a germ-free status on myelin-related characteristics, and highlight the adaptive properties of myelination as a result of environmental manipulation.
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Enfermedad de Huntington/microbiología , Proteínas de la Mielina/metabolismo , Vaina de Mielina/patología , Sustancia Blanca/microbiología , Animales , Bacterias/aislamiento & purificación , Cuerpo Calloso/metabolismo , Cuerpo Calloso/microbiología , Modelos Animales de Enfermedad , Enfermedad de Huntington/patología , Ratones Transgénicos , Vaina de Mielina/metabolismo , Plasticidad Neuronal/fisiología , Oligodendroglía/metabolismo , Corteza Prefrontal/metabolismo , Sustancia Blanca/patologíaRESUMEN
We investigated the contributions of commensal bacteria to brain structural maturation by magnetic resonance imaging and behavioral tests in four and 12 weeks old C57BL/6J specific pathogen free (SPF) and germ free (GF) mice. SPF mice had increased volumes and fractional anisotropy in major gray and white matter areas and higher levels of myelination in total brain, major white and grey matter structures at either four or 12 weeks of age, demonstrating better brain maturation and organization. In open field test, SPF mice had better mobility and were less anxious than GF at four weeks. In Morris water maze, SPF mice demonstrated better spatial and learning memory than GF mice at 12 weeks. In fear conditioning, SPF mice had better contextual memory than GF mice at 12 weeks. In three chamber social test, SPF mice demonstrated better social novelty than GF mice at 12 weeks. Our data demonstrate numerous significant differences in morphological brain organization and behaviors between SPF and GF mice. This suggests that commensal bacteria are necessary for normal morphological development and maturation in the grey and white matter of the brain regions with implications for behavioral outcomes such as locomotion and cognitive functions.
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Conducta Animal , Encéfalo/crecimiento & desarrollo , Encéfalo/microbiología , Microbiota , Animales , Conducta Animal/fisiología , Encéfalo/diagnóstico por imagen , Recuento de Células , Femenino , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/crecimiento & desarrollo , Sustancia Gris/microbiología , Imagen por Resonancia Magnética , Masculino , Aprendizaje por Laberinto/fisiología , Ratones Endogámicos C57BL , Vaina de Mielina/microbiología , Neuronas/citología , Neuronas/microbiología , Tamaño de los Órganos , Conducta Social , Memoria Espacial/fisiología , Organismos Libres de Patógenos Específicos , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/crecimiento & desarrollo , Sustancia Blanca/microbiologíaRESUMEN
Microbial communities reside in healthy tissues but are often disrupted during disease. Bacterial genomes and proteins are detected in brains from humans, nonhuman primates, rodents and other species in the absence of neurological disease. We investigated the composition and abundance of microbiota in frozen and fixed autopsied brain samples from patients with multiple sclerosis (MS) and age- and sex-matched nonMS patients as controls, using neuropathological, molecular and bioinformatics tools. 16s rRNA sequencing revealed Proteobacteria to be the dominant phylum with restricted diversity in cerebral white matter (WM) from MS compared to nonMS patients. Both clinical groups displayed 1,200-1,400 bacterial genomes/cm3 and low bacterial rRNA:rDNA ratios in WM. RNAseq analyses showed a predominance of Proteobacteria in progressive MS patients' WM, associated with increased inflammatory gene expression, relative to a broader range of bacterial phyla in relapsing-remitting MS patients' WM. Although bacterial peptidoglycan (PGN) and RNA polymerase beta subunit immunoreactivities were observed in all patients, PGN immunodetection was correlated with demyelination and neuroinflammation in MS brains. Principal component analysis revealed that demyelination, PGN and inflammatory gene expression accounted for 86% of the observed variance. Thus, inflammatory demyelination is linked to an organ-specific dysbiosis in MS that could contribute to underlying disease mechanisms.
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Encéfalo/microbiología , Enfermedades Desmielinizantes/microbiología , Disbiosis/microbiología , Esclerosis Múltiple/microbiología , Proteobacteria/aislamiento & purificación , Sustancia Blanca/microbiología , Actinobacteria/clasificación , Actinobacteria/genética , Actinobacteria/aislamiento & purificación , Adulto , Anciano , Anciano de 80 o más Años , Autopsia , Encéfalo/patología , Estudios de Casos y Controles , Cianobacterias/clasificación , Cianobacterias/genética , Cianobacterias/aislamiento & purificación , ADN Bacteriano/genética , Enfermedades Desmielinizantes/patología , Disbiosis/patología , Femenino , Humanos , Inflamación , Masculino , Microbiota/genética , Persona de Mediana Edad , Esclerosis Múltiple/patología , Análisis de Componente Principal , Proteobacteria/clasificación , Proteobacteria/genética , ARN Ribosómico 16S/genética , Sustancia Blanca/patologíaRESUMEN
OBJECTIVE: We determined whether Gram-negative bacterial molecules are associated with Alzheimer disease (AD) neuropathology given that previous studies demonstrate Gram-negative Escherichia coli bacteria can form extracellular amyloid and Gram-negative bacteria have been reported as the predominant bacteria found in normal human brains. METHODS: Brain samples from gray and white matter were studied from patients with AD (n = 24) and age-matched controls (n = 18). Lipopolysaccharide (LPS) and E coli K99 pili protein were evaluated by Western blots and immunocytochemistry. Human brain samples were assessed for E coli DNA followed by DNA sequencing. RESULTS: LPS and E coli K99 were detected immunocytochemically in brain parenchyma and vessels in all AD and control brains. K99 levels measured using Western blots were greater in AD compared to control brains (p < 0.01) and K99 was localized to neuron-like cells in AD but not control brains. LPS levels were also greater in AD compared to control brain. LPS colocalized with Aß1-40/42 in amyloid plaques and with Aß1-40/42 around vessels in AD brains. DNA sequencing confirmed E coli DNA in human control and AD brains. CONCLUSIONS: E coli K99 and LPS levels were greater in AD compared to control brains. LPS colocalized with Aß1-40/42 in amyloid plaques and around vessels in AD brain. The data show that Gram-negative bacterial molecules are associated with AD neuropathology. They are consistent with our LPS-ischemia-hypoxia rat model that produces myelin aggregates that colocalize with Aß and resemble amyloid-like plaques.