RESUMO
Iron deficiency affects nearly 2 billion people worldwide, with pregnant women and young children being most severely impacted. Sustained anemia during the first year of life can cause cognitive, attention and motor deficits, which may persist despite iron supplementation. We conducted iTRAQ analyses on cerebrospinal fluid (CSF) from infant monkeys (Macaca mulatta) to identify differential protein expression associated with early iron deficiency. CSF was collected from 5 iron-sufficient and 8 iron-deficient anemic monkeys at weaning age (6-7 months) and again at 12-14 months. Despite consumption of iron-fortified food after weaning, which restored hematological indices into the normal range, expression of 5 proteins in the CSF remained altered. Most of the proteins identified are involved in neurite outgrowth, migration or synapse formation. The results reveal novel ways in which iron deficiency undermines brain growth and results in aberrant neuronal migration and connections. Taken together with gene expression data from rodent models of iron deficiency, we conclude that significant alterations in neuroconnectivity occur in the iron-deficient brain, which may persist even after resolution of the hematological anemia. The compromised brain infrastructure could account for observations of behavioral deficits in children during and after the period of anemia.
Assuntos
Anemia Ferropriva/líquido cefalorraquidiano , Proteínas do Líquido Cefalorraquidiano/análise , Proteômica/métodos , Fatores Etários , Anemia Ferropriva/complicações , Anemia Ferropriva/dietoterapia , Anemia Ferropriva/embriologia , Animais , Dano Encefálico Crônico/líquido cefalorraquidiano , Dano Encefálico Crônico/etiologia , Resinas de Troca de Cátion , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia por Troca Iônica/métodos , Feminino , Compostos Ferrosos/administração & dosagem , Compostos Ferrosos/uso terapêutico , Alimentos Fortificados , Macaca mulatta , Masculino , Desnutrição/fisiopatologia , Modelos Animais , Proteínas do Tecido Nervoso/líquido cefalorraquidiano , Proteínas do Tecido Nervoso/deficiência , Fragmentos de Peptídeos/análise , Gravidez , Complicações na Gravidez/fisiopatologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , DesmameRESUMO
Perinatal brain damage may result in impaired neurological development in extremely preterm infants. The underlying pathophysiological mechanisms are complex, and biomarkers of prognostic value are not available. The aim of this study was to analyze soluble Fas (sFas) concentrations in the cerebrospinal fluid (CSF) representative for involvement of apoptotic processes in preterm infants developing posthemorrhagic hydrocephalus (PHHC) and to link them to white matter damage (WMD) diagnosed by cranial ultrasound. A total of 29 preterm infants with PHHC were included in the study; 17 of them had signs of cystic WMD (cWMD) on ultrasound examinations. CSF samples were obtained at first ventriculostomy, and results were compared to those of a reference group of 24 preterm and term infants without neurologic diseases. sFas concentrations were elevated in CSF samples of PHHC patients compared to the reference group. In patients with cWMD, sFas concentrations were significantly higher than in patients without cWMD. These results indicate that apoptosis via the Fas pathway is involved in the pathogenesis of cWMD in the context of PHHC, and that sFas in the CSF may serve as a marker of cWMD development.
Assuntos
Dano Encefálico Crônico/líquido cefalorraquidiano , Hidrocefalia/líquido cefalorraquidiano , Doenças do Prematuro/líquido cefalorraquidiano , Hemorragias Intracranianas/complicações , Receptor fas/líquido cefalorraquidiano , Apoptose , Biomarcadores/líquido cefalorraquidiano , Dano Encefálico Crônico/diagnóstico por imagem , Dano Encefálico Crônico/etiologia , Humanos , Hidrocefalia/complicações , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/diagnóstico por imagem , Doenças do Prematuro/etiologia , Estudos Prospectivos , UltrassonografiaRESUMO
BACKGROUND: Central nervous system (CNS) irradiation has been replaced by systemic high-dose methotrexate (MTX) and intrathecal MTX in acute lymphoblastic leukemia treatment due to the risk of late effects. However, treatment without CNS irradiation might also cause brain damage. PROCEDURE: Cerebrospinal fluid (CSF) was analyzed in 121 patients in an attempt to detect CNS injury. Seventy-three samples were analyzed for neuron-specific enolase (NSE), 108 for glial fibrillary acidic protein (GFAp), 110 for neurofilament protein light chain (NFp), and 70 for ascorbyl radical (AsR). Samples were taken at day 0, 8, 15, and 29 during induction treatment, including intrathecal MTX. Levels at days 8, 15, and 29 were compared with the levels before treatment. RESULTS: NSE levels were 9.0 (+/-3.5) microg/L (mean (+/-SD)) at day 0, 15.0 (+/-5.3) at day 8 (P < 0.001), 13.6 (+/-4.7) at day 15 (P < 0.001) and 11.1 (+/-4.3) at day 29 (P < 0.001). GFAp were 177 (+/-98) ng/L at day 0, 206 (+/-101) at day 8 (P < 0.001), 200 (+/-106) at day 15 (n.s.) and 228 (+/-137) at day 29 (P < 0.001). NFp were below the detection limit 125 ng/L at day 0 in all 110 CSF samples analyzed, and increased significantly above the detection limit in 6/77 samples at day 8, in 11/84 at day 15 and in 22/91 at day 29. The AsR content did not change significantly. CONCLUSIONS: Levels of NSE, GFAp, and NFp increased in CSF, which can be interpreted as early signs of brain damage. AsR levels do not show any convincing signs of oxidative stress.
Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Biomarcadores/líquido cefalorraquidiano , Encéfalo/efeitos dos fármacos , Proteína Glial Fibrilar Ácida/líquido cefalorraquidiano , Metotrexato/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Dano Encefálico Crônico/líquido cefalorraquidiano , Dano Encefálico Crônico/induzido quimicamente , Lesões Encefálicas , Criança , Pré-Escolar , Ácido Desidroascórbico/análogos & derivados , Ácido Desidroascórbico/líquido cefalorraquidiano , Feminino , Humanos , Lactente , Masculino , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Fosfopiruvato Hidratase/líquido cefalorraquidiano , RadioimunoensaioRESUMO
BACKGROUND: Hashimoto's encephalopathy (HE) is a condition believed to complicate Hashimoto's thyroiditis (HT). The diagnosis is suspected in the presence of high levels of serum anti-thyroid antibodies. We have recently demonstrated that in patients with HE there is an intrathecal synthesis of anti-thyroid antibodies, and concluded that the diagnosis of HE should be based on this cerebrospinal fluid (CSF) finding. OBJECTIVE: getting an estimate of the prevalence of the disease, verifying the association with HT and investigating the pathogenetic role of anti-thyroid antibodies. METHODS: 34-months prospective study in a hospital setting serving a community of 150,000 people. Patients with unexplained symptoms of acute or subacute encephalopathy or myelopathy or with a history of thyroid disorders were selected for the measurement of anti-thyroid antibodies. In the presence of high serum levels of autoantibodies, the same tests were performed in the CSF. RESULTS: Twelve patients had increased concentrations of serum autoantibodies but HE was diagnosed only in nine patients. The estimated prevalence of HE is 2.1/100,000. Only six HE patients had also HT. Four patients received corticosteroids, five patients were not treated. Five patients improved, four patients spontaneously, one patient after corticosteroids. Repeated CSF examinations showed that the titer of CSF autoantibodies did not correlate with the clinical stage of the disease nor was influenced by corticosteroids. In addition, the course of symptoms was independent of therapy. CONCLUSIONS: The association of encephalopathy and high titers of anti-thyroid antibodies is not sufficient to make a diagnosis of HE. Independent of the clinical status of the thyroid gland, the intrathecal synthesis of autoantibodies is a distinctive marker of this elusive condition.
Assuntos
Autoanticorpos/líquido cefalorraquidiano , Dano Encefálico Crônico/líquido cefalorraquidiano , Dano Encefálico Crônico/imunologia , Líquido Cefalorraquidiano/imunologia , Glândula Tireoide/imunologia , Tireoidite Autoimune/imunologia , Adolescente , Corticosteroides/uso terapêutico , Adulto , Idoso , Autoanticorpos/sangue , Autoanticorpos/imunologia , Dano Encefálico Crônico/epidemiologia , Líquido Cefalorraquidiano/metabolismo , Comorbidade , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Glândula Tireoide/fisiopatologia , Tireoidite Autoimune/epidemiologiaRESUMO
OBJECT: Hydrocephalus is characterised by elevated intracranial pressure (ICP) and gives rise to brain damage. The aim of this study was to investigate the significance of brain specific proteins as markers in the evaluation of brain damage in hydrocephalus. Therefore we determined the levels of four brain specific proteins in cerebrospinal fluid (CSF) and serum of symptomatic hydrocephalic patients. METHODS: During 41 CSF shunt-operations (both primarily placed shunts and shunt-revisions) CSF and blood samples were obtained and analysed for neuron-specific enolase (NSE), S-100b, glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP). The results were compared with an age-matched control group. Patients with varying clinical symptoms, denoting different levels of increased intracranial pressure prior to surgery, were included in this study. RESULTS: We observed significantly increased CSF-levels of S-100b and GFAP in the hydrocephalic patients, whereas NSE and MBP were markedly increased only in patients with very severe symptoms. Serum levels of all proteins were only minimally increased and did not correlate with CSF-levels. The slightly elevated levels of CSF-NSE in most of the patients suggest only subtle neuronal damage, which is not related to permanent neurological symptoms. The elevated levels of S-100b and GFAP are indicative of a reactive astrogliosis, which has also been demonstrated in histopathological studies. No demyelination seems to occur, according to the normal levels of MBP observed in this study. CONCLUSIONS: Although CSF levels of brain specific proteins are elevated in hydrocephalic patients, indicating brain damage due to hydrocephalus, neither CSF- nor serum-concentrations of brain specific proteins seem to be valuable tools in the clinical evaluation of the severity of hydrocephalus.
Assuntos
Dano Encefálico Crônico/sangue , Dano Encefálico Crônico/líquido cefalorraquidiano , Proteína Glial Fibrilar Ácida/sangue , Proteína Glial Fibrilar Ácida/líquido cefalorraquidiano , Hidrocefalia/sangue , Hidrocefalia/líquido cefalorraquidiano , Proteína Básica da Mielina/sangue , Proteína Básica da Mielina/líquido cefalorraquidiano , Fosfopiruvato Hidratase/sangue , Fosfopiruvato Hidratase/líquido cefalorraquidiano , Proteínas S100/sangue , Proteínas S100/líquido cefalorraquidiano , Adolescente , Dano Encefálico Crônico/etiologia , Criança , Pré-Escolar , Feminino , Humanos , Hidrocefalia/complicações , Masculino , Fatores de Crescimento Neural , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Subunidade beta da Proteína Ligante de Cálcio S100 , Índice de Gravidade de DoençaRESUMO
Two siblings with familial encephalopathy, calcification of the basal ganglia, and cerebrospinal fluid lymphocytosis, constituting the triad of Aicardi-Goutieres syndrome, are reported. This syndrome resembles congenital intrauterine infections, which must be meticulously excluded. Aicardi-Goutieres syndrome is extremely rare and is being reported from the Arab world for the first time to our knowledge.
Assuntos
Doenças dos Gânglios da Base/genética , Dano Encefálico Crônico/genética , Calcinose/genética , Atrofia , Doenças dos Gânglios da Base/líquido cefalorraquidiano , Doenças dos Gânglios da Base/diagnóstico , Dano Encefálico Crônico/líquido cefalorraquidiano , Dano Encefálico Crônico/diagnóstico , Calcinose/líquido cefalorraquidiano , Calcinose/diagnóstico , Córtex Cerebral/patologia , Criança , Pré-Escolar , Aberrações Cromossômicas , Mapeamento Cromossômico , Cromossomos Humanos Par 3 , Consanguinidade , Diagnóstico Diferencial , Feminino , Seguimentos , Genes Recessivos/genética , Humanos , Lactente , Recém-Nascido , Linfocitose/líquido cefalorraquidiano , Linfocitose/diagnóstico , Linfocitose/genética , Masculino , Síndrome , Tomografia Computadorizada por Raios XRESUMO
To evaluate the spectrum and regulation of matrix metalloproteinases (MMPs) in bacterial meningitis (BM), concentrations of MMP-2, MMP-3, MMP-8, and MMP-9 and endogenous inhibitors of metalloproteinases (TIMP-1 and TIMP-2) were measured in the cerebrospinal fluid (CSF) of 27 children with BM. MMP-8 and MMP-9 were detected in 91% and 97%, respectively, of CSF specimens from patients but were not detected in control patients. CSF levels of MMP-9 were higher (P<.05) in 5 patients who developed hearing impairment or secondary epilepsy than in those who recovered without neurological deficits. Levels of MMP-9 correlated with concentrations of TIMP-1 (P<.001) and tumor necrosis factor-alpha (P=.03). Repeated lumbar punctures showed that levels of MMP-8 and MMP-9 were regulated independently and did not correlate with the CSF cell count. Therefore, MMPs may derive not only from granulocytes infiltrating the CSF space but also from parenchymal cells of the meninges and brain. High concentrations of MMP-9 are a risk factor for the development of postmeningitidal neurological sequelae.
Assuntos
Barreira Hematoencefálica , Dano Encefálico Crônico/líquido cefalorraquidiano , Infecções por Haemophilus/líquido cefalorraquidiano , Haemophilus influenzae , Metaloproteinase 8 da Matriz/líquido cefalorraquidiano , Metaloproteinase 9 da Matriz/líquido cefalorraquidiano , Meningites Bacterianas/líquido cefalorraquidiano , Meningite Meningocócica/líquido cefalorraquidiano , Meningite Pneumocócica/líquido cefalorraquidiano , Dano Encefálico Crônico/patologia , Criança , Pré-Escolar , Seguimentos , Infecções por Haemophilus/patologia , Humanos , Lactente , Metaloproteinase 2 da Matriz/líquido cefalorraquidiano , Metaloproteinase 3 da Matriz/líquido cefalorraquidiano , Meningites Bacterianas/patologia , Meningite Meningocócica/patologia , Meningite Pneumocócica/patologia , Neisseria meningitidis , Estudos Retrospectivos , Punção Espinal , Streptococcus pneumoniae , Fatores de Tempo , Inibidor Tecidual de Metaloproteinase-1/líquido cefalorraquidiano , Inibidor Tecidual de Metaloproteinase-2/líquido cefalorraquidiano , Fator de Necrose Tumoral alfa/análiseRESUMO
We measured the level of myelin basic protein (MBP) in the cerebrospinal fluid (CSF) of patients with various kinds of tumors, including malignant tumors, using radioimmunoassay. The CSF had been obtained by lumbar puncture through an Ommaya reservoir or a shunt device placed in the lateral ventricle. The level of MBP was high (> 4 ng/ml) in the patients with meningeal dissemination of malignant tumors, but in those who showed a good response to chemotherapy and/or radiation, it decreased or returned to the normal level, with improvement on the computed tomography and magnetic resonance imaging, cytological, general CSF, and neurological findings. Of seven malignant gliomas without CSF dissemination, six showed an elevated level of MBP before selective intra-arterial chemotherapy with a combination of etoposide and cisplatin administered via a microcatheter placed at A1, M1, P1-P2, and the basilar top. All CSF specimens obtained during the period of the intra-arterial chemotherapy showed an abnormally high (> 4 ng/ml) level of MBP that exceeded the prechemotherapy level. The MBP level decreased or returned to normal in the patients with a good response to chemotherapy after intra-arterial chemotherapy. In some patients with multiple metastatic brain tumors, the MBP level was elevated before treatment and returned to normal after treatment (surgical removal, chemotherapy, and/or irradiation) in all except one. Thus, there was a clear correlation between the timing of treatment and changes in imaging studies and MBP levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Biomarcadores Tumorais/líquido cefalorraquidiano , Neoplasias Encefálicas/líquido cefalorraquidiano , Neoplasias Meníngeas/líquido cefalorraquidiano , Proteína Básica da Mielina/líquido cefalorraquidiano , Adulto , Idoso , Astrocitoma/líquido cefalorraquidiano , Astrocitoma/diagnóstico , Astrocitoma/secundário , Astrocitoma/terapia , Dano Encefálico Crônico/líquido cefalorraquidiano , Dano Encefálico Crônico/diagnóstico , Dano Encefálico Crônico/terapia , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Terapia Combinada , Irradiação Craniana , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Seguimentos , Glioblastoma/líquido cefalorraquidiano , Glioblastoma/diagnóstico , Glioblastoma/secundário , Glioblastoma/terapia , Humanos , Infusões Intra-Arteriais , Linfoma de Células B/líquido cefalorraquidiano , Linfoma de Células B/diagnóstico , Linfoma de Células B/terapia , Linfoma Difuso de Grandes Células B/líquido cefalorraquidiano , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/terapia , Masculino , Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/secundário , Neoplasias Meníngeas/terapia , Meningioma/líquido cefalorraquidiano , Meningioma/diagnóstico , Meningioma/secundário , Meningioma/terapia , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
In a cohort of victims of traumatic brain injury, 18 out of 50 patients had a plasma tumour necrosis factor (TNF) concentration above 2 pg/ml within 24 h of injury (mean 12.19, SD 45.96 pg/ml). Twenty-six had CSF samples available of which 17 demonstrated TNF concentrations above 1 pg/ml (mean 3.98, SD 3.61 pg/ml). We conclude that traumatized brain parenchyma is a significant source of TNF activity and implicate the cytokine in cellular metabolic derangements following head injury.
Assuntos
Dano Encefálico Crônico/líquido cefalorraquidiano , Lesões Encefálicas/líquido cefalorraquidiano , Fator de Necrose Tumoral alfa/líquido cefalorraquidiano , Adolescente , Adulto , Idoso , Barreira Hematoencefálica/fisiologia , Dano Encefálico Crônico/diagnóstico , Dano Encefálico Crônico/cirurgia , Edema Encefálico/líquido cefalorraquidiano , Edema Encefálico/diagnóstico , Edema Encefálico/cirurgia , Lesões Encefálicas/diagnóstico , Lesões Encefálicas/cirurgia , Hemorragia Cerebral/líquido cefalorraquidiano , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/cirurgia , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Escala de Coma de Glasgow , Humanos , Masculino , Pessoa de Meia-IdadeAssuntos
Dano Encefálico Crônico/líquido cefalorraquidiano , Encefalopatias/líquido cefalorraquidiano , Proteínas do Líquido Cefalorraquidiano/análise , Neoplasias Encefálicas/líquido cefalorraquidiano , Criança , Pré-Escolar , Eletroforese em Gel de Ágar , Encefalite/líquido cefalorraquidiano , Epilepsia/líquido cefalorraquidiano , Feminino , Humanos , Lactente , Masculino , Meningite/líquido cefalorraquidianoRESUMO
S-100 protein was determined by Particle Counting ImmunoAssay in the CSF of patients with various neurological disorders. With a limit of sensitivity of 2.5 micrograms/l this brain-specific protein was detected only in samples from patients with acute damage of the central nervous system, particularly in compression of the spinal cord by tumour, ischaemic disorders, subarachnoïd bleeding and haematoma, and viral or suspected viral infections. Our results support the assumption that S-100 is a reliable index of central nervous system damage and that changes in its concentration could have a prognostic value.
Assuntos
Dano Encefálico Crônico/diagnóstico , Doenças do Sistema Nervoso Central/diagnóstico , Proteínas do Tecido Nervoso/líquido cefalorraquidiano , Proteínas S100/líquido cefalorraquidiano , Dano Encefálico Crônico/líquido cefalorraquidiano , Doenças do Sistema Nervoso Central/líquido cefalorraquidiano , Eletroforese em Gel de Poliacrilamida , Humanos , PrognósticoAssuntos
Dano Encefálico Crônico/etiologia , Encéfalo/metabolismo , Leucemia Linfoide/terapia , Metotrexato/efeitos adversos , Radioterapia/efeitos adversos , Fosfatase Ácida/líquido cefalorraquidiano , Aspartato Aminotransferases/líquido cefalorraquidiano , Encéfalo/efeitos dos fármacos , Encéfalo/efeitos da radiação , Dano Encefálico Crônico/líquido cefalorraquidiano , Carboidratos/líquido cefalorraquidiano , Proteínas do Líquido Cefalorraquidiano/análise , Criança , Creatina Quinase/líquido cefalorraquidiano , AMP Cíclico/líquido cefalorraquidiano , Humanos , L-Lactato Desidrogenase/líquido cefalorraquidiano , Leucemia Linfoide/metabolismoRESUMO
A study of the incidence of fat-laden cells (compound granular corpuscles) in the cerebrospinal fluid in infants indicating that a high level of these cells (over 40% of cells) is invariably associated with a bad prognosis and lower levels of these cells can give a useful indication of brain damage in children with meningitis and ventriculitis.