RESUMO
The impact of the group B streptococcus (GBS)-induced maternal inflammation on offspring's brain has not yet been investigated despite GBS being one of the most frequent bacteria colonizing or infecting pregnant women. According to our hypothesis GBS-induced maternal immune activation plays a role in offspring perinatal brain damage and subsequent neurodisabilities such as autism. Using a new preclinical rat model of maternal inflammation triggered by inactivated GBS, we demonstrated placental, neuropathological and behavioral impacts on offspring. GBS-exposed placentas presented cystic lesions and polymorphonuclear infiltration located within the decidual/maternal side of the placenta, contrasting with macrophagic infiltration and necrotic areas located in the labyrinth/fetal compartment of the placenta after lipopolysaccharide-induced maternal inflammation. Brain damage featured lateral ventricles widening, predominately in the male, reduction of periventricular external capsules thickness, oligodendrocyte loss, and disorganization of frontoparietal subcortical tissue with no glial proliferation. Autistic hallmarks were found in offspring exposed to GBS, namely deficits in motor behavior, social and communicative impairments, i.e. profound defects in the integration and response to both acoustic and chemical signals that are predominant modes of communication in rats. Surprisingly, only male offspring were affected by these combined autistic-like traits. Our results show for the first time that materno-fetal inflammatory response to GBS plays a role in the induction of placental and cerebral insults, remarkably recapitulating cardinal features of human autism such as gender dichotomy and neurobehavioral traits. Unlike other models of prenatal inflammatory brain damage (induced by viral/toll-like receptor 3 (TLR3) or Gram-negative/TLR4), maternal inflammation resulting from GBS/TLR2 interactions induced a distinctive pattern of chorioamnionitis and cerebral injuries. These results also provide important evidence that beyond genetic influences, modifiable environmental factors play a role in both the occurrence of autism and its gender imbalance.
Assuntos
Transtorno Autístico/etiologia , Lesões Encefálicas/patologia , Encéfalo/patologia , Placenta/metabolismo , Infecções Estreptocócicas/microbiologia , Streptococcus agalactiae , Animais , Animais Recém-Nascidos , Comportamento Animal , Encéfalo/efeitos dos fármacos , Encéfalo/microbiologia , Lesões Encefálicas/microbiologia , Feminino , Lipopolissacarídeos/farmacologia , Masculino , Fibras Nervosas Mielinizadas/efeitos dos fármacos , Fibras Nervosas Mielinizadas/patologia , Gravidez , RatosRESUMO
The fragile X syndrome usually results from CGG repeats expansion and methylation of the FMR1 gene leading to the absence of expression of its encoded protein, fragile X mental retardation protein (FMRP). Therefore, its diagnosis is traditionally based on the detection of these molecular alterations. As an alternative, FMRP-based screening methods have been proposed over the years. Most of them are based on immunohistochemistry analyses applied to a restricted number of lymphocytes (100) or hair roots (10-20) with limited diagnosis potential. In this study, we describe a truly quantitative approach using a new model, the blood platelet, which can be recovered easily with very high purity (99.9%). FMRP levels in platelets were first measured in a control population (n = 124) and reference values were established. FMRP measurements were also performed in confirmed fragile X subjects. Receiver operating characteristic curve analysis has shown that our test can easily discriminate fragile X males and females from controls (area under curve, AUC = 0.948). Cognitive functions were also assessed in these individuals using age-specific Wechsler Intelligence Scales for Children and the Vineland Adaptive Behavior Scales. A proportional relationship between FMRP levels, intelligence quotient and adaptive behavior was observed among fragile X individuals, suggesting that our test would be able to detect fragile X cases and may predict cognitive functions.
Assuntos
Plaquetas/metabolismo , Proteína do X Frágil da Deficiência Intelectual/genética , Síndrome do Cromossomo X Frágil/genética , Adolescente , Adulto , Southern Blotting , Estudos de Casos e Controles , Criança , Pré-Escolar , Cognição , Estudos de Avaliação como Assunto , Feminino , Síndrome do Cromossomo X Frágil/diagnóstico , Testes Genéticos , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Adulto JovemRESUMO
Arteriopathies are the commonest cause of arterial ischaemic stroke (AIS) in children. Repeated vascular imaging in children with AIS demonstrated the existence of a 'transient cerebral arteriopathy' (TCA), characterized by lenticulostriate infarction due to non-progressive unilateral arterial disease affecting the supraclinoid internal carotid artery and its proximal branches. To further characterize the course of childhood arteriopathies, and to differentiate TCA from progressive arterial disease, we studied the long-term evolution of unilateral anterior circulation arteriopathy, and explored predictors of stroke outcome and recurrence. From three consecutive cohorts in London, Paris and Utrecht, we reviewed radiological studies and clinical charts of 79 previously healthy children with anterior circulation AIS and unilateral intracranial arteriopathy of the internal carotid bifurcation, who underwent repeated vascular imaging. The long-term evolution of arteriopathy was classified as progressive or TCA. Clinical and imaging characteristics were compared between both groups. Logistic regression modelling was used to determine possible predictors of the course of arteriopathy, functional outcome and recurrence. After a median follow-up of 1.4 years, 5 of 79 children (6%) had progressive arteriopathy, with increasing unilateral disease or bilateral involvement. In the others (94%), the course of arteriopathy was classified as TCA. In 23% of TCA patients, follow-up vascular imaging showed complete normalization, the remaining 77% had residual arterial abnormalities, with improvement in 45% and stabilization in 32%. Stroke was preceded by chickenpox in 44% of TCA patients, and in none of the patients with progressive arteriopathies. Most infarcts were localized in the basal ganglia. In 14 (19%) of TCA patients, transient worsening of the arterial lesion was demonstrated before the arteriopathy stabilized or improved. Thirteen TCA patients (18%) had a recurrent stroke or TIA. Thirty TCA patients (41%) had a good neurological outcome, compared with none of the five patients with progressive arteriopathy. Arterial occlusion, moyamoya vessels and ACA involvement were more frequent in progressive arteriopathies. Cortical infarct localization was significantly associated with poor neurological outcome (OR 6.14, 95% CI 1.29-29.22, P = 0.02), while there was a trend for occlusive arterial disease to predict poor outcome (OR 3.00, 95% CI 0.98-9.23, P = 0.06). Progressive arteriopathy was associated with recurrence (OR 18.77, 95%CI 1.94-181.97, P = 0.01). The majority of childhood unilateral intracranial anterior circulation arteriopathies (94%) have a course that is consistent with TCA, in which transient worsening is common. Although the arterial inflammation probably causing TCA is 'transient', most children are left with permanent arterial abnormalities and residual neurological deficits.
Assuntos
Doenças Arteriais Intracranianas/patologia , Adolescente , Angiografia Digital , Isquemia Encefálica/complicações , Isquemia Encefálica/patologia , Angiografia Cerebral , Varicela/complicações , Varicela/patologia , Criança , Pré-Escolar , Progressão da Doença , Feminino , Seguimentos , Herpesvirus Humano 3 , Humanos , Lactente , Doenças Arteriais Intracranianas/classificação , Doenças Arteriais Intracranianas/complicações , Trombose Intracraniana/complicações , Trombose Intracraniana/patologia , Ataque Isquêmico Transitório/complicações , Ataque Isquêmico Transitório/patologia , Imageamento por Ressonância Magnética , Masculino , Prognóstico , Recidiva , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/patologiaRESUMO
Genetically determined leukoencephalopathies comprise a group of rare inherited white matter disorders. The majority are progressive diseases resulting in early death. We performed a cross-sectional pilot study including 55 parents from 36 families to assess the level of stress experienced by parents of patients with genetically determined leukoencephalopathies, aged 1 month to 12 years. Thirty-four mothers and 21 fathers completed the Parenting Stress Index-4th Edition. One demographic questionnaire was completed per family. Detailed clinical data was gathered on all patients. Statistical analysis was performed with total stress percentile score as the primary outcome. Mothers and fathers had significantly higher stress levels compared with the normative sample; 20% of parents had high levels of stress whereas 11% had clinically significant levels of stress. Mothers and fathers had comparable total stress percentile scores. We identified pediatric behavioral difficulties and gross motor function to be factors influencing stress in mothers. Our study is the first to examine parental stress in this population and highlights the need for parental support early in the disease course. In this pilot study, we demonstrated that using the Parenting Stress Index-4th Edition to assess stress levels in parents of patients with genetically determined leukoencephalopathies is feasible, leads to valuable and actionable results, and should be used in larger, prospective studies.
Assuntos
Leucoencefalopatias/psicologia , Pais/psicologia , Estresse Psicológico/psicologia , Adulto , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Projetos Piloto , Inquéritos e QuestionáriosRESUMO
A critical issue in animal models of perinatal brain injury is to adapt the pertinent pathophysiological scenarios to their corresponding developmental window in order to induce neuropathological and behavioral characteristics reminiscent to perinatal cerebral palsy (CP). A major problem in most of these animal models designed up to now is that they do not present motor deficits characteristic of CP. Using a unique rat paradigm of prenatal inflammation combined to an early postnatal hypoxia-ischemia pertinent to the context of very early premature human newborns, we were interested in finding out if such experimental conditions might reproduce both histological damages and behavioral deficits previously described in the human context. We showed that exposure to lipopolysaccharide (LPS) or hypoxia-ischemia (H/I) induced behavioral alterations in animals subjected to forced motor activity. When both LPS and H/I aggressions were combined, the motor deficits reached their highest intensity and affected both spontaneous and forced motor activities. LPS+H/I-exposed animals also showed extensive bilateral cortical and subcortical lesions of the motor networks affecting the frontal cortices and underlying white matters fascicles, lenticular nuclei and the substantia nigra. These neuropathological lesions and their associated motor behavioral deficits are reminiscent of those observed in very preterm human neonates affected by subsequent CP and validate the value of the present animal model to test new therapeutic strategies which might open horizons for perinatal neuroprotection.
Assuntos
Paralisia Cerebral/etiologia , Hipóxia-Isquemia Encefálica/complicações , Lipopolissacarídeos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Fatores Etários , Animais , Animais Recém-Nascidos , Comportamento Animal , Proteínas de Ligação ao Cálcio/metabolismo , Contagem de Células , Modelos Animais de Doenças , Feminino , Lateralidade Funcional , Proteína Glial Fibrilar Ácida/metabolismo , Hipóxia-Isquemia Encefálica/patologia , Resposta de Imobilidade Tônica/fisiologia , Locomoção/fisiologia , Masculino , Proteínas dos Microfilamentos , Gravidez , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos , Ratos Endogâmicos Lew , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
Chorioamnionitis and intrauterine growth retardation (IUGR) are risk factors for cerebral palsy (CP). Common bacteria isolated in chorioamnionitis include group B Streptococcus (GBS) serotypes Ia and III. Little is known about the impact of placental inflammation induced by different bacteria, including different GBS strains. We aimed to test the impact of chorioamnionitis induced by two common GBS serotypes (GBSIa and GBSIII) on growth and neuromotor outcomes in the progeny. Dams were exposed at the end of gestation to either saline, inactivated GBSIa or GBSIII. Inactivated GBS bacteria invaded placentas and triggered a chorioamnionitis featured by massive polymorphonuclear cell infiltrations. Offspring exposed to GBSIII - but not to GBSIa - developed IUGR, persisting beyond adolescent age. Male rats in utero exposed to GBSIII traveled a lower distance in the Open Field test, which was correlating with their level of IUGR. GBSIII-exposed rats presented decreased startle responses to acoustic stimuli beyond adolescent age. GBS-exposed rats displayed a dysmyelinated white matter in the corpus callosum adjacent to thinner primary motor cortices. A decreased density of microglial cells was detected in the mature corpus callosum of GBSIII-exposed males - but not females - which was correlating positively with the primary motor cortex thickness. Altogether, our results demonstrate a causal link between pathogen-induced acute chorioamnionitis and (1) IUGR, (2) serotype- and sex-specific neuromotor impairments and (3) abnormal development of primary motor cortices, dysmyelinated white matter and decreased density of microglial cells.
Assuntos
Paralisia Cerebral/etiologia , Corioamnionite/microbiologia , Retardo do Crescimento Fetal/fisiopatologia , Placenta/microbiologia , Efeitos Tardios da Exposição Pré-Natal/microbiologia , Infecções Estreptocócicas/complicações , Streptococcus agalactiae/patogenicidade , Animais , Animais Recém-Nascidos , Comportamento Animal , Lesões Encefálicas/etiologia , Lesões Encefálicas/patologia , Paralisia Cerebral/patologia , Feminino , Masculino , Placenta/imunologia , Gravidez , Ratos , Infecções Estreptocócicas/microbiologiaRESUMO
BACKGROUND: Group B streptococcus (GBS) is the main bacteria that infects pregnant women and can cause abortion and chorioamnionitis. The impact of GBS effects on human trophoblast cells remains largely elusive, and actions toward anti-inflammatory strategies in pregnancy are needed. A potent anti-inflammatory molecule, uvaol is a triterpene from olive oil and its functions in trophoblasts are unknown. We aimed to analyze biomechanical and functional effects of inactivated GBS in trophoblast cells, with the addition of uvaol to test potential benefits. METHODS: HTR-8/SVneo cells were treated with uvaol and incubated with inactivated GBS. Cell viability and death were analyzed. Cellular elasticity and topography were accessed by atomic force microscopy. Nitrite production was evaluated by Griess reaction. Nuclear translocation of NFkB p65 was detected by immunofluorescence and Th1/Th2 cytokines by bead-based multiplex assay. RESULTS: GBS at 108â¯CFU increased cell death, which was partially prevented by uvaol. Cell stiffness, cytoskeleton organization and morphology were changed by GBS, and uvaol partially restored these alterations. Nuclear translocation of NFkB p65 began 15â¯min after GBS incubation and uvaol inhibited this process. GBS decreased IL-4 secretion and increased IL-1ß, IFN-γ and IL-2, whereas uvaol reverted this. CONCLUSIONS: The increased inflammation and cell death caused by GBS correlated with biomechanical and cytoskeleton changes found in trophoblast cells, while uvaol was effective its protective role. GENERAL SIGNIFICANCE: Uvaol is a natural anti-inflammatory product efficient against GBS-induced inflammation and it has potential to be acquired through diet in order to prevent GBS deleterious effects in pregnancy.
Assuntos
Streptococcus agalactiae/patogenicidade , Triterpenos/farmacologia , Trofoblastos/efeitos dos fármacos , Trofoblastos/microbiologia , Animais , Transporte Biológico , Fenômenos Biomecânicos , Morte Celular , Linhagem Celular , Núcleo Celular/metabolismo , Sobrevivência Celular , Chlorocebus aethiops , Citocinas/metabolismo , Feminino , Humanos , NF-kappa B/metabolismo , Nitritos/metabolismo , Gravidez , Células Th1/metabolismo , Trofoblastos/metabolismo , Células VeroRESUMO
Neuroimaging and management advances require review of indications for excluding cerebral venous sinus (sinovenous) thrombosis (CSVT) in children. Our goals were to examine (i) clinical presentations of CSVT, (ii) prothrombotic risk factors and other predisposing events, (iii) clinical and radiological features of brain lesions in CSVT compared with arterial stroke, and (iv) predictors of outcome. We studied 42 children with CSVT from five European paediatric neurology stroke registries. Patients aged from 3 weeks to 13 (median 5.75) years (27 boys; 64%) presented with lethargy, anorexia, headache, vomiting, seizures, focal signs or coma and with CSVT on neuroimaging. Seventeen had prior chronic conditions; of the 25 previously well patients, 23 had recent infections, eight became dehydrated and six had both. Two children had a history compatible with prior CSVT. Anaemia and/or microcytosis (21 probable iron deficiency, five haemolytic, including two with sickle cell disease and one with beta-thalassaemia) was as common (62%) as prothrombotic disorder (13/21 screened). High factor VIII and homozygosity for the thermolabile methylene tetrahydrofolate reductase polymorphism were the commonest prothrombotic disorders. The superficial venous system was involved in 32 patients, the deep in six, and both in four. Data on the 13 children with bland infarction and the 12 with haemorrhage in the context of CSVT were compared with those from 88 children with ischaemic (AIS) and 24 with haemorrhagic (AHS) arterial stroke. In multiple logistic regression, iron deficiency, parietal infarction and lack of caudate involvement independently predicted CSVT rather than arterial disease. Five patients died, three acutely, one after recurrence and one after 6 months being quadriparetic and blind. Follow-up ranged from 0.5 to 10 (median 1) years. Twenty-six patients (62%) had sequelae: pseudotumour cerebri in 12 and cognitive and/or behavioural disabilities in 14, associated with epilepsy in three, hemiparesis in two and visual problems in two. Eighteen patients, including six with haemorrhage, were anticoagulated. Older age [odds ratio (OR) 1.54, 95% confidence limits (CI) 1.12, 2.13, P = 0.008], lack of parenchymal abnormality (OR 0.17, 95% CI 0.02, 1.56, P = 0.1), anticoagulation (OR 24.2, 95% CI 1.96, 299) and lateral and/or sigmoid sinus involvement (OR 16.2, 95% CI 1.62, 161, P = 0.02) were independent predictors of good cognitive outcome, although the last predicted pseudotumour cerebri. Death was associated with coma at presentation. Of 19 patients with follow-up magnetic resonance (MR) venography, three had persistent occlusion, associated with anaemia and longer prodrome. A low threshold for CT or MR venography in children with acute neurological symptoms is essential. Nutritional deficiencies may be modifiable risk factors. A paediatric anticoagulation trial may be required, after the natural history has been further established from registries of cases with and without treatment.
Assuntos
Trombose dos Seios Intracranianos/diagnóstico , Trombose dos Seios Intracranianos/etiologia , Adolescente , Anticoagulantes/uso terapêutico , Criança , Pré-Escolar , Doença Crônica , Diagnóstico Diferencial , Feminino , Humanos , Lactente , Recém-Nascido , Hipertensão Intracraniana/terapia , Imageamento por Ressonância Magnética , Masculino , Prognóstico , Recidiva , Sistema de Registros , Fatores de Risco , Trombose dos Seios Intracranianos/tratamento farmacológico , Acidente Vascular Cerebral/diagnóstico , Trombofilia/etiologia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
We studied 43 children with extensive brain gyral anomalies diagnosed radiologically and defined by (a) the absence or paucity of sulci over cortical areas affecting at least two lobes in each hemisphere, and (b) the absence or reduction of interdigitation between gray and white matter. We correlated the clinical, EEG, and genetic findings with the imaging features. A seemingly homogeneous group of patients (group A, n = 30) presented a common imaging pattern characterized by four features: (1) a thickened neocortex, (2) widened lateral ventricles, (3) apparent verticalization and widening of sylvian fissures, and (4) bilateral and symmetric distribution of the abnormalities. Another group of patients (group B, n = 13) exhibited heterogeneous imaging anomalies, termed "nonlissencephalic brain malformation," differing in at least one of the following four ways from the radiologic criteria defining group A: absence of verticalization of sylvian fissures (n = 12), thin neocortex (n = 2), normal-size lateral ventricles (n = 2), and asymmetric brain defects (n = 3). In group A, some clinical features had a significantly lower frequency (p < or = 0.01) than in group B: microcephaly, a complete lack of postural development, and intractable epilepsy. There was a significant relationship, but only in group A, between the degree of gyral anomalies and the extent of neurodevelopmental delay. Some EEG patterns (rapid rhythms and delta-theta rhythms) were highly specific for the group A patients. There was lower risk of familial recurrence in group A (recurrence of convolutional anomalies was 3.5% of sibship in group A versus 44% of sibship in group B, p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Córtex Cerebral/anormalidades , Córtex Cerebral/fisiopatologia , Criança , Eletroencefalografia , Feminino , Humanos , Lactente , MasculinoRESUMO
BACKGROUND: Periventricular leukomalacia (PVL) affects the developing white matter of neonatal brain. Inflammatory and infectious conditions are implicated in the cause of PVL. METHODS: The authors investigated the in situ expression of proinflammatory cytokines (interleukin-1beta and -6, tumor necrosis factor alpha [TNFalpha]), adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1) and inflammatory cell markers (CD68, leukocyte common antigen, human leukocyte antigen II) in 19 neonatal brains with PVL. The authors compared the findings with matched non-PVL brains. RESULTS: The inflammatory reaction detected at the early stage of PVL extends until the latest phase of cystic cavitation, though at an attenuated level. There is high expression of TNFalpha and to a lesser extent interleukin-1beta; interleukin-6 remains undetectable. Cytokine immunoreactivity is detected in PVL cases both with and without infection. However, cytokine production was higher with infection. A different pattern of cytokine expression was observed in anoxic brains without PVL: TNFalpha immunoreactivity was significantly lower than the PVL group. CONCLUSIONS: An immune-mediated inflammatory process may play a role in PVL. TNFalpha, a myelinotoxic factor, may be the major mediator.
Assuntos
Encéfalo/imunologia , Encéfalo/metabolismo , Citocinas/metabolismo , Encefalite/imunologia , Encefalite/metabolismo , Leucomalácia Periventricular/imunologia , Leucomalácia Periventricular/metabolismo , Antígenos de Superfície/metabolismo , Encéfalo/patologia , Paralisia Cerebral/imunologia , Paralisia Cerebral/metabolismo , Paralisia Cerebral/patologia , Feminino , Humanos , Recém-Nascido , Interleucina-1/metabolismo , Interleucina-6/metabolismo , Leucomalácia Periventricular/patologia , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Neuroglia/metabolismo , Neuroglia/patologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Proinflammatory cytokines were reported to be implicated in the pathogenesis of perinatal white matter lesions. The authors document for the first time the in situ detection of interleukin-2 and interleukin-2 receptor (IL-2R) in these human white matter lesions. These results suggest that interleukin-2, reported to be toxic to oligodendrocytes and myelin, could play a role in the molecular cascade leading to white matter damage in periventricular leukomalacia.
Assuntos
Encéfalo/metabolismo , Encéfalo/patologia , Recém-Nascido/metabolismo , Recém-Nascido Prematuro , Interleucina-2/biossíntese , Citocinas/análise , Citocinas/biossíntese , Feminino , Humanos , Mortalidade Infantil , Recém-Nascido Prematuro/metabolismo , Interleucina-2/análise , Masculino , Estatísticas não ParamétricasRESUMO
The authors describe the clinical, radiologic, and pathologic features of a neonatal spinal neurenteric cyst (NC) presenting with long-lasting fever and acute myelopathy, and compare this observation with other infants reported in the literature. This observation shows that NC must be considered in the differential diagnosis of acute myelopathy with persistent fever in infancy. Fever is attributed to degenerative changes in the NC, triggering inflammatory cell infiltration and tumor necrosis factor alpha secretion.
Assuntos
Febre de Causa Desconhecida/etiologia , Defeitos do Tubo Neural/diagnóstico , Compressão da Medula Espinal/diagnóstico , Vértebras Torácicas/anormalidades , Consanguinidade , Diagnóstico Diferencial , Feminino , Humanos , Recém-Nascido , Defeitos do Tubo Neural/genética , Defeitos do Tubo Neural/patologia , Compressão da Medula Espinal/genética , Compressão da Medula Espinal/patologia , Vértebras Torácicas/patologiaRESUMO
Monocytes but not unstimulated lymphocytes adhered to human neurons and astrocytes in primary culture, as demonstrated by double labeling. The expression of VCAM-1 was higher on neurons than on astrocytes, whereas that of beta 1, alpha 1, alpha 2, alpha 4 and alpha 5 chains from the integrins and of ICAM-1 was identical on both types of cells. The expression on neurons of ICAM-1, but not of integrins, was up-regulated by exogenous tumor necrosis factor (TNF) alpha, interleukin (IL)-1 alpha and interferon (IFN)-gamma. The same was observed on astrocytes associated with a sharp increase in the expression of VCAM-1. Adhesion between monocytes and neurons or astrocytes was 80% inhibited by mAbs directed against the CR3 determinant on monocytes or against ICAM-1 on neural cells but not by any of the other mAbs against adhesion proteins that were tested. Finally, the level of endogenous production of IL-1 alpha and TNF alpha was greatly increased after the adhesion of monocytes to CNS cells.
Assuntos
Astrócitos/fisiologia , Citocinas/farmacologia , Molécula 1 de Adesão Intercelular/fisiologia , Antígeno de Macrófago 1/fisiologia , Monócitos/fisiologia , Neurônios/fisiologia , Anticorpos Monoclonais/imunologia , Adesão Celular/efeitos dos fármacos , Células Cultivadas , Humanos , Linfócitos/fisiologia , Magnésio/farmacologia , Temperatura , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
UNLABELLED: The haemorrhagic shock and encephalopathy syndrome (HSES) is a devastating disease. The aetiology of this syndrome is unknown, and, despite intensive treatment, the outcome is often fatal or associated with severe neurological sequelae. OBJECTIVE: To assess the neurological features and potential prognostic markers of the disease. DESIGN: Retrospective study. SETTING: Division of Neuropaediatrics in a children's university hospital. PATIENTS AND METHODS: Fourteen patients fulfilling the HSES criteria out of 42 children admitted with fever and shock to the Paediatric Intensive Care Unit between 1986 and 1994, were analysed for clinical, biological, neuroradiological, EEG and neuropathological findings. RESULTS: The patients (age range from 2 to 33 months) were found at night or in the morning either comatous (n = 3) or convulsing (n = 11). All but one were healthy before admission, although eight had had a brief prodromal infectious disease. All were febrile (mean body temperature 39.9 degrees C +/-0.9 degrees). Seasonal clustering during the winter months was observed. Coma and seizures with frequent status epilepticus were the main neurological manifestations. All children recovered from their multiple organ failure within a few days. Seven died (50%); four survivors had neurological sequelae (29%) with a developmental quotient (DQ) of 50% or less in three and a DQ of 75% in one and three infants (21%) had normal outcomes. Computed tomography (CT) displayed a diffuse area of low density mainly in the cerebral cortex and intraventricular and parenchymal haemorrhages. Magnetic resonance imaging (MRI) showed haemorrhagic cortical lesions. Postmortem examination of the brain conducted in three patients showed necrotic and haemorrhagic lesions, mainly in cortical areas. Comparison of the children with adverse outcome (death or neurological sequelae) with those with normal outcome revealed that predictors of poor outcome were status epilepticus (p = 0.003) and coma for more than 24 h (p = 0.01). Infants without disseminated intravascular coagulation, without a biphasic course and without brain hypodensities or haemorrhages on CT scans performed at least 4 days after onset had a normal neurodevelopmental outcome. CONCLUSION: The central nervous system appeared to be the main target of the HSES lesions. The most common outcome was brain death or severe brain damage. Further studies with a larger sample are necessary to determine whether the prognostic indicators we identified are reliable.
Assuntos
Encefalopatias/fisiopatologia , Choque Hemorrágico/fisiopatologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encefalopatias/diagnóstico por imagem , Encefalopatias/patologia , Pré-Escolar , Coma , Progressão da Doença , Eletroencefalografia , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Prontuários Médicos , Necrose , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Convulsões , Choque Hemorrágico/diagnóstico por imagem , Choque Hemorrágico/patologia , Síndrome , Tomografia Computadorizada por Raios XRESUMO
We report a case of cerebellitis displaying a severe neurologic onset but with spontaneous recovery, challenging the use of immunomodulatory treatment.
Assuntos
Doenças Cerebelares/diagnóstico , Encefalomielite Aguda Disseminada/diagnóstico , Adjuvantes Imunológicos/uso terapêutico , Doenças Cerebelares/tratamento farmacológico , Cerebelo/patologia , Pré-Escolar , Encefalomielite Aguda Disseminada/tratamento farmacológico , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Exame Neurológico , Remissão EspontâneaRESUMO
Repeated clinical evaluation and cerebral arteriography during the evolution of ischemic strokes of idiopathic origin allowed us to characterize a transient cerebral arteriopathy. We retrospectively studied the clinical characteristics, course, and neuroimaging features of this disorder in nine children. Of 34 children with ischemic strokes seen consecutively between 1984 and 1995, 9 (26%) were diagnosed as having transient attack of the cerebral arterial wall, termed transient cerebral arteriopathy. All of these patients had previously been in good health. The mean age at the time of the first stroke was 6 years (range, 2 9/12 years to 13 4/12 years). All children presented with acute hemiplegia. A recurrence of the stroke took place 3 months at the latest after the initial infarct in three children (mean clinical follow-up 2 7/12 years). Cerebral imaging in all the patients showed small subcortical infarcts located in basal ganglia or internal capsule. Arteriography revealed multifocal lesions of the arterial wall (focal stenosis or segmental narrowing), mostly located in the initial parts of basal arteries of the carotid system. Longitudinal arteriographic follow-up showed initial worsening of these arterial lesions (n = 5) for a maximum duration of 7 months followed by complete regression (n = 2), improvement (n = 5), or stabilization of the lesions (n = 2). Five patients had a complete clinical recovery. Further studies are necessary to confirm a presumed inflammatory cause of this arteriopathy.
Assuntos
Artérias Cerebrais/diagnóstico por imagem , Transtornos Cerebrovasculares/diagnóstico por imagem , Ataque Isquêmico Transitório/diagnóstico por imagem , Doença Aguda , Adolescente , Transtornos Cerebrovasculares/complicações , Transtornos Cerebrovasculares/tratamento farmacológico , Criança , Pré-Escolar , Feminino , Humanos , Ataque Isquêmico Transitório/complicações , Ataque Isquêmico Transitório/prevenção & controle , Masculino , Inibidores da Agregação Plaquetária/uso terapêutico , RadiografiaRESUMO
Adenylosuccinase deficiency, an autosomal recessive inborn error of purine synthesis, was first described in 1984 by Jaeken and Van den Berghe (reviewed in J Inher Metab Dis 20;1997:193). The cardinal features are variable psychomotor delay often accompanied by epilepsy and autistic features. Diagnosis is made by detection of abnormal purine metabolites in body fluids. We report a girl who presented with early onset epilepsy, associated with acquired microcephaly and severe psychomotor retardation, as the most prominent symptoms.
Assuntos
Adenilossuccinato Liase/deficiência , Encefalopatias Metabólicas Congênitas/complicações , Epilepsia/etiologia , Epilepsia/metabolismo , Microcefalia/etiologia , Microcefalia/metabolismo , Idade de Início , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/fisiopatologia , Encefalopatias Metabólicas Congênitas/diagnóstico , Encefalopatias Metabólicas Congênitas/patologia , Pré-Escolar , Progressão da Doença , Eletroencefalografia , Epilepsia/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Microcefalia/patologiaRESUMO
BACKGROUND: Neurogenic sphincter dysfunction may result from acute transverse myelopathy. The aim of this paper is to study the course of such a dysfunction and to propose management techniques. PATIENTS AND METHODS: The files of 21 children admitted at the mean age of 8 years 5 months (2 to 14 years, 8 months) for acute transverse myelopathy were retrospectively studied. RESULTS: Bladder sphincter dysfunction occurred in the first days of disease in 85% of these patients. Abnormal perception of micturition was one of the most constant and specific symptoms. Anorectal function was also impaired. Complete regressive course was noted in 38% of patients, minor sequellae in 39% and major sequellae beyond 6 months of course in 23%. None upper tract deterioration was noted after 3 years of course. Factors of favorable prognosis were early motor function recovery (especially recommencement of walking before 20 days) and early management of bladder dysfunction (inability to void had better prognosis than urinary incontinence). CONCLUSION: Early systematic bladder drainage in case of inability to void might be essential for improved prognosis.
Assuntos
Mielite Transversa/complicações , Bexiga Urinaria Neurogênica/etiologia , Doença Aguda , Adolescente , Canal Anal , Criança , Pré-Escolar , Árvores de Decisões , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Bexiga Urinaria Neurogênica/fisiopatologia , Bexiga Urinaria Neurogênica/terapiaRESUMO
BACKGROUND: Benign intracranial hypertension is due to an increased intracranial pressure of unknown cause. The initial symptoms, complications and associations with medical conditions are discussed. CASE REPORT: A 6-year-old girl developed symptoms of benign intracranial hypertension following reduction of oral corticosteroid therapy. Laboratory studies and head-computed tomographic scan were normal. Examination of the optic discs showed bilateral papilledema and the cerebrospinal fluid pressure was increased. The patient was given prednisone therapy 1 mg/kg daily initially, associated with acetazolamide, and removal of 25 mL of cerebrospinal fluid. All the symptoms resolved and the treatment was gradually decreased. The child developed no further visual failure. CONCLUSION: Benign intracranial hypertension with the risk of permanent visual loss is a complication underrecognized in children. All patients receiving large doses of the corticosteroids who complain of headache or blurring vision, particularly following a reduction of corticosteroid dosage, should have an ophtalmoscopic examination to exclude this complication.
Assuntos
Acetazolamida/uso terapêutico , Anti-Inflamatórios/efeitos adversos , Prednisona/efeitos adversos , Pseudotumor Cerebral/induzido quimicamente , Administração Oral , Anti-Inflamatórios/uso terapêutico , Criança , Terapia Combinada , Diuréticos/uso terapêutico , Feminino , Humanos , Síndrome Nefrótica/tratamento farmacológico , Prednisona/uso terapêutico , Pseudotumor Cerebral/diagnóstico , Pseudotumor Cerebral/terapia , Punção Espinal , Fatores de TempoRESUMO
BACKGROUND: Neuroradiological features of hypertensive encephalopathy are not yet well-known. PATIENTS AND METHODS: The clinical manifestations, neuroradiological aspects and treatment of four patients suffering from hypertensive encephalopathy were studied; special attention was paid to manifestations presented by one patient which appeared representative of the usual manifestations of hypertensive encephalopathy. RESULTS: The main clinical features were visual disturbances (n = 4); altered consciousness (n = 2) and seizures (n = 3). Visual disturbances resulted from cortical lesions (n = 4) associated with optic nerve damage and retinopathy (n = 2). Cerebral imaging showed low density images (CT scan) and hypersignal (MRI, T2 sequence) located in parieto-occipital cortical ribbon and adjacent white matter from the first 24 hours following the onset of neurologic symptoms. In the studied patient, the abnormal images resolved within 1 month after the onset of the disease. Unilateral infarction of the anterior visual pathway affected two patients in whom: 1) hypertension remaining undetected for a long time was revealed by neurological signs; 2) visual impairment was preceded by an hypotensive episode induced by antihypertensive therapy. CONCLUSIONS: Neuroradiological features of hypertensive encephalopathy are useful in establishing the diagnosis. A gradual reduction of blood pressure could prevent the risk of visual complications.