RESUMO
OBJECTIVE: External ventricular drains (EVDs) are commonly used in the neurosurgical population. However, very few pediatric neurosurgery studies are available regarding EVD-associated infection rates with antibiotic-impregnated EVD catheters. The authors previously published a large pediatric cohort study analyzing nonantibiotic-impregnated EVD catheters and risk factors associated with infections. In this study, they aimed to analyze the EVD-associated infection rate after implementation of antibiotic-impregnated EVD catheters. METHODS: A retrospective observational cohort of pediatric patients (younger than 18 years of age) who underwent a burr hole for antibiotic-impregnated EVD placement and who were admitted to a quaternary care ICU between January 2011 and January 2019 were reviewed. The ventriculostomy-associated infection rate in patients with antibiotic-impregnated EVD catheters was compared to the authors' historical control of patients with nonantibiotic-impregnated EVD catheters. RESULTS: Two hundred twenty-nine patients with antibiotic-impregnated EVD catheters were identified. Neurological diagnostic categories included externalization of an existing shunt (externalized shunt) in 34 patients (14.9%); brain tumor (tumor) in 77 patients (33.6%); intracranial hemorrhage (ICH) in 27 patients (11.8%); traumatic brain injury (TBI) in 6 patients (2.6%); and 85 patients (37.1%) were captured in an "other" category. Two of 229 patients (0.9% of all patients) had CSF infections associated with EVD management, totaling an infection rate of 0.99 per 1000 catheter days. This is a significantly lower infection rate than was reported in the authors' previously published analysis of the use of nonantibiotic-impregnated EVD catheters (0.9% vs 6%, p = 0.00128). CONCLUSIONS: In their large pediatric cohort, the authors demonstrated a significant decline in ventriculostomy-associated CSF infection rate after implementation of antibiotic-impregnated EVD catheters at their institution.
Assuntos
Antibacterianos/uso terapêutico , Catéteres/efeitos adversos , Derivações do Líquido Cefalorraquidiano/efeitos adversos , Ventriculostomia/efeitos adversos , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Drenagem/efeitos adversos , Feminino , Humanos , Lactente , Infecções/líquido cefalorraquidiano , Infecções/tratamento farmacológico , Masculino , Procedimentos Neurocirúrgicos/efeitos adversos , Estudos RetrospectivosRESUMO
Infections and inflammatory processes have been associated with the development of schizophrenia and affective disorders; however, no study has yet systematically reviewed all available studies on cerebrospinal fluid (CSF) immune alterations. We aimed to systematically review the CSF immunological findings in schizophrenia spectrum and affective disorders. We identified all studies investigating CSF inflammatory markers in persons with schizophrenia or affective disorders published prior to March 23, 2017 searching PubMed, CENTRAL, EMBASE, Psychinfo, and LILACS. Literature search, data extraction and bias assessment were performed by two independent reviewers. Meta-analyses with standardized mean difference (SMD) including 95% confidence intervals (CI) were performed on case-healthy control studies. We identified 112 CSF studies published between 1942-2016, and 32 case-healthy control studies could be included in meta-analyses. Studies varied regarding gender distribution, age, disease duration, treatment, investigated biomarkers, and whether recruitment happened consecutively or based on clinical indication. The CSF/serum albumin ratio was increased in schizophrenia (1 study [54 patients]; SMD = 0.71; 95% CI 0.33-1.09) and affective disorders (4 studies [298 patients]; SMD = 0.41; 95% CI 0.23-0.60, I2 = 0%), compared to healthy controls. Total CSF protein was elevated in both schizophrenia (3 studies [97 patients]; SMD = 0.41; 95% CI 0.15-0.67, I2 = 0%) and affective disorders (2 studies [53 patients]; SMD = 0.80; 95% CI 0.39-1.21, I2 = 0%). The IgG ratio was increased in schizophrenia (1 study [54 patients]; SMD = 0.68; 95% CI 0.30-1.06), whereas the IgG Albumin ratio was decreased (1 study [32 patients]; SMD = -0.62; 95% CI -1.13 to -0.12). Interleukin-6 (IL-6) levels (7 studies [230 patients]; SMD = 0.55; 95% CI 0.35-0.76; I2 = 1%) and IL-8 levels (3 studies [95 patients]; SMD = 0.46; 95% CI 0.17-0.75, I2 = 0%) were increased in schizophrenia but not significantly increased in affective disorders. Most of the remaining inflammatory markers were not significantly different compared to healthy controls in the meta-analyses. However, in the studies which did not include healthy controls, CSF abnormalities were more common, and two studies found CSF dependent re-diagnosis in 3.2-6%. Current findings suggest that schizophrenia and affective disorders may have CSF abnormalities including signs of blood-brain barrier impairment and inflammation. However, the available evidence does not allow any firm conclusion since all studies showed at least some degree of bias and vastly lacked inclusion of confounding factors. Moreover, only few studies investigated the same parameters with healthy controls and high-quality longitudinal CSF studies are lacking, including impact of psychotropic medications, lifestyle factors and potential benefits of anti-inflammatory treatment in subgroups with CSF inflammation.
Assuntos
Inflamação/metabolismo , Transtornos do Humor/fisiopatologia , Esquizofrenia/fisiopatologia , Biomarcadores/líquido cefalorraquidiano , Líquido Cefalorraquidiano/imunologia , Líquido Cefalorraquidiano/metabolismo , Feminino , Humanos , Infecções/líquido cefalorraquidiano , Infecções/fisiopatologia , Inflamação/líquido cefalorraquidiano , Masculino , Transtornos do Humor/líquido cefalorraquidiano , Transtornos Psicóticos/líquido cefalorraquidiano , Transtornos Psicóticos/fisiopatologia , Esquizofrenia/líquido cefalorraquidianoRESUMO
In-vitro metabolite and drug detection rely on designed materials-based analytical platforms, which are universally used in biomedical research and clinical practice. However, metabolic analysis in bio-samples needs tedious sample preparation, due to the sample complexity and low molecular abundance. A further challenge is to construct diagnostic tools. Herein, we developed a platform using silver nanoshells. We synthesized SiO2@Ag with tunable shell structures by multi-cycled silver mirror reactions. Optimized nanoshells achieved direct laser desorption/ionization mass spectrometry in 0.5 µL of bio-fluids. We applied these nanoshells for disease diagnosis and therapeutic evaluation. We identified patients with postoperative brain infection through daily monitoring and glucose quantitation in cerebrospinal fluid. We measured drug distribution in blood and cerebrospinal fluid systems and validated the function of blood-brain/cerebrospinal fluid-barriers for pharmacokinetics. Our work sheds light on the design of materials for advanced metabolic analysis and precision diagnostics.Preparation of samples for diagnosis can affect the detection of biomarkers and metabolites. Here, the authors use a silver nanoparticle plasmonics approach for the detection of biomarkers in patients as well as investigate the distribution of drugs in serum and cerebral spinal fluid.
Assuntos
Técnicas de Laboratório Clínico , Nanoconchas/química , Prata , Encefalopatias/líquido cefalorraquidiano , Encefalopatias/diagnóstico , Glucose/líquido cefalorraquidiano , Humanos , Infecções/líquido cefalorraquidiano , Infecções/diagnóstico , Preparações Farmacêuticas/sangue , Preparações Farmacêuticas/líquido cefalorraquidiano , Farmacocinética , Complicações Pós-Operatórias/líquido cefalorraquidiano , Complicações Pós-Operatórias/diagnósticoRESUMO
Until now, the identification of micro-organisms has been based on the cultural and biochemical characteristics of bacterial and fungal species. Recently, Mass Spectrometry type Matrix-Assisted Laser Desorption Ionization-Time of Flight (MALDI-TOF MS) was developed in clinical microbiology laboratories. This new technology allows identification of micro-organisms directly from colonies of bacteria and fungi within few minutes. In addition, it can be used to identify germs directly from positive blood culture bottles or directly from urine samples. Other ways are being explored to expand the use of MALDI-TOF in clinical microbiology laboratories. Indeed, some studies propose to detect bacterial antibiotic resistance while others compare strains within species for faster strain typing. The main objective of this review is to update data from the recent literature for different applications of MALDI-TOF technique in microbiological diagnostic routine.
Assuntos
Técnicas de Laboratório Clínico/métodos , Técnicas Microbiológicas/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Animais , Bactérias/química , Bactérias/classificação , Técnicas de Laboratório Clínico/normas , Testes Diagnósticos de Rotina/métodos , Testes Diagnósticos de Rotina/normas , Fungos/química , Fungos/classificação , Humanos , Infecções/líquido cefalorraquidiano , Infecções/microbiologia , Infecções/urina , Testes de Sensibilidade Microbiana , Técnicas Microbiológicas/normas , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/normasRESUMO
BACKGROUND: Bolt-kit systems are increasingly used as an alternative to conventional external cerebrospinal fluid (CSF) drainage systems. Since 2009 we regularly utilize bolt-kit external ventricular drainage (EVD) systems with silver-bearing catheters inserted manually with a hand drill and skull screws for emergency ventriculostomy. For non-emergency situations, we use conventional ventriculostomy with subcutaneous tunneled silver-bearing catheters, performed in the operating room with a pneumatic drill. This retrospective analysis compared the two techniques in terms of infection rates. METHODS: 152 patients (aged 17-85 years, mean=55.4 years) were included in the final analysis; 95 received bolt-kit silver-bearing catheters and 57 received conventionally implanted silver-bearing catheters. The primary endpoint combined infection parameters: occurrence of positive CSF culture, colonization of catheter tips, or elevated CSF white blood cell counts (>4/µl). Secondary outcome parameters were presence of microorganisms in CSF or on catheter tips. Incidence of increased CSF cell counts and number of patients with catheter malposition were also compared. RESULTS: The primary outcome, defined as analysis of combined infection parameters (occurrence of either positive CSF culture, colonization of the catheter tips or raised CSF white blood cell counts >4/µl)was not significantly different between the groups (58.9% bolt-kit group vs. 63.2% conventionally implanted group, p=0.61, chi-square-test). The bolt-kit group was non-inferior and not superior to the conventional group (relative risk reduction of 6.7%; 90% confidence interval: -19.9% to 25.6%). Secondary outcomes showed no statistically significant difference in the incidence of microorganisms in CSF (2.1% bolt-kit vs. 5.3% conventionally implanted; p=0.30; chi-square-test). CONCLUSIONS: This analysis indicates that silver-bearing EVD catheters implanted with a bolt-kit system outside the operating room do not significantly elevate the risk of CSF infection as compared to conventional implant methods.
Assuntos
Cateteres de Demora/efeitos adversos , Drenagem/efeitos adversos , Infecções/etiologia , Ventriculostomia/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cateteres de Demora/microbiologia , Drenagem/instrumentação , Feminino , Humanos , Infecções/líquido cefalorraquidiano , Infecções/microbiologia , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Cytokines and cytokine receptor concentrations increase in plasma and cerebrospinal fluid (CSF) of patients following subarachnoid haemorrhage (SAH). The relationship between plasma and CSF cytokines, and factors affecting this, are not clear. METHODS: To help define the relationship, paired plasma and cerebrospinal fluid (CSF) samples were collected from patients subject to ventriculostomy. Concentrations of key inflammatory cytokines, interleukin (IL)-1ß, IL-1 receptor antagonist (IL-1Ra), IL-1 receptor 2, IL-6, IL-8, IL-10, tumour necrosis factor (TNF)-α, and TNF receptors (TNF-R) 1 and 2 were determined by immunoassay of CSF and plasma from 21 patients, where samples were available at three or more time points. RESULTS: Plasma concentrations of IL-1ß, IL-1Ra, IL-10, TNF-α and TNF-R1 were similar to those in CSF. Plasma TNF-R2 and IL-1R2 concentrations were higher than in CSF. Concentrations of IL-8 and IL-6 in CSF were approximately10 to 1,000-fold higher than in plasma. There was a weak correlation between CSF and plasma IL-8 concentrations (r = 0.26), but no correlation for IL-6. Differences between the central and peripheral pattern of IL-6 were associated with episodes of ventriculostomy-related infection (VRI). A VRI was associated with CSF IL-6 >10,000 pg/mL (P = 0.0002), although peripheral infection was not significantly associated with plasma IL-6. CONCLUSIONS: These data suggest that plasma cytokine concentrations cannot be used to identify relative changes in the CSF, but that measurement of CSF IL-6 could provide a useful marker of VRI.
Assuntos
Citocinas/sangue , Citocinas/líquido cefalorraquidiano , Infecções/diagnóstico , Receptores de Citocinas/metabolismo , Hemorragia Subaracnóidea/sangue , Hemorragia Subaracnóidea/líquido cefalorraquidiano , Adulto , Idoso , Feminino , Humanos , Infecções/sangue , Infecções/líquido cefalorraquidiano , Infecções/etiologia , Masculino , Pessoa de Meia-Idade , Ventriculostomia/efeitos adversos , Ventriculostomia/métodosRESUMO
OBJECTIVE: Intraventricular reservoirs (IVRs) are used to drain cerebrospinal fluid (CSF) in neonates with post-hemorrhagic ventricular dilatation (PHVD). The objectives of this case-control study were to evaluate changes in CSF parameters in serial IVR taps and to compare CSF parameters in culture-positive and -negative specimens. STUDY DESIGN: Clinical and laboratory data from serial (up to 7) reservoir taps at 5- to 8-day intervals were collected on preterm neonates with PHVD and IVR insertion. RESULT: The median (range) gestational age and birth weight of our cohort (n=52) was 26 (23 to 33) weeks and 796 (450 to 1620) grams. Significant decreases in percentage of CSF neutrophils and protein were noted in later taps, compared with the first tap at insertion of IVR. Five (9.6%) infants had positive CSF cultures on 10 occasions. Compared with negative specimens (n=266), the mean (s.d.) proportion of neutrophils in CSF (55% (33) vs 26% (23)) was significantly higher and ratio of CSF to serum glucose significantly lower (0.19 (0.08) vs 0.29 (0.13)) in culture-positive specimens (n=10). The area under the curve was 0.82 (95% confidence interval (CI) 0.72 to 0.93) for CSF white blood cell (WBC) count, 0.79 (95% CI 0.68 to 0.90) for CSF protein and 0.75 (95% CI 0.56 to 0.95) for percentage of neutrophils. The sensitivities and specificities for diagnosis of infection was 90 and 63% for CSF WBC count > 42 mm(-3), 89 and 58% for CSF protein at > 250 mg dl(-1) and 80 and 67% for CSF neutrophil proportion >31.5%. CONCLUSION: CSF parameters from IVR taps, specifically proportion of neutrophils and proteins are higher at insertion and progressively normalize over time. Although they vary widely, CSF WBC, protein and neutrophil proportion using higher cut-off values have good sensitivity in the diagnosis of infection.
Assuntos
Ventrículos Cerebrais/metabolismo , Proteínas do Líquido Cefalorraquidiano/análise , Doenças do Prematuro/líquido cefalorraquidiano , Recém-Nascido Prematuro/líquido cefalorraquidiano , Infecções/líquido cefalorraquidiano , Estudos de Casos e Controles , Ventrículos Cerebrais/microbiologia , Humanos , Lactente , Recém-Nascido , Neutrófilos , Sensibilidade e EspecificidadeRESUMO
Hashimoto's encephalopathy is an under-recognized and rare disease that presents a diagnostic conundrum since many features are suggestive of infectious etiologies and yet treatment is immunosuppressive medications. We describe a case of a male with a history of recurrent seizures who presented with a subacute onset of confusion, persistent leukocytosis and fever while on immunosuppressant therapy, whose response to high dose steroids was incomplete and who achieved a complete remission of all symptoms when plasmapheresis was initiated. A negative cerebrospinal fluid (CSF) and serum microbiological testing in a patient with an abnormal EEG, increased CSF protein, and elevated thyroid antibodies should prompt consideration of Hashimoto's encephalopathy. If after treating with high dose steroids, there is a sub-optimal clinical response, plasmapheresis should be considered.
Assuntos
Encefalopatias/diagnóstico , Encefalopatias/terapia , Doença de Hashimoto/diagnóstico , Doença de Hashimoto/terapia , Infecções/diagnóstico , Infecções/terapia , Encefalopatias/líquido cefalorraquidiano , Diagnóstico Diferencial , Encefalite , Doença de Hashimoto/líquido cefalorraquidiano , Humanos , Imunossupressores/uso terapêutico , Infecções/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade , Plasmaferese/métodos , RecidivaRESUMO
Proteins of the interleukin-1 (IL-1) system include the secreted agonist IL-1beta, and the receptor antagonist IL-1ra, both competing for binding to the IL-1 receptor (IL-1R). IL-1beta and IL-1ra are highly inducible under different forms of stress, such as excitatory neurotransmitter excess occurring during seizures, in infection and inflammation, and during neurotrauma. In each of these conditions induction of IL-1beta precedes that of IL-1ra, resulting in up to 10-20-fold elevation of IL-1beta concentrations. Consequently, IL-1beta induces the elevation of other proinflammatory molecules, including IL-6, IL-1R1, COX2, and iNOS, as well as of IL-1ra. Elevation of IL-1ra is of key importance for quenching the inflammatory response at the IL-1R1 as part of an autoregulatory loop. In seizures, IL-1ra is a strong anticonvulsant and in IL-1beta-dependent fever, a powerful antipyretic. In traumatic brain injury (TBI), the ability of patients to mount an IL-1ra response, as measured in the CSF, strongly correlated with the neurological outcome. Selective induction or pharmacological application of IL-1ra may be sparing neurons in seizures and neurotrauma.
Assuntos
Lesões Encefálicas/metabolismo , Sistema Nervoso Central/patologia , Febre/metabolismo , Interleucina-1beta/fisiologia , Neurônios/patologia , Convulsões/metabolismo , Animais , Lesões Encefálicas/líquido cefalorraquidiano , Lesões Encefálicas/patologia , Sistema Nervoso Central/fisiologia , Modelos Animais de Doenças , Febre/líquido cefalorraquidiano , Febre/patologia , Humanos , Infecções/líquido cefalorraquidiano , Infecções/metabolismo , Infecções/patologia , Inflamação/líquido cefalorraquidiano , Inflamação/metabolismo , Inflamação/patologia , Proteína Antagonista do Receptor de Interleucina 1/biossíntese , Proteína Antagonista do Receptor de Interleucina 1/genética , Proteína Antagonista do Receptor de Interleucina 1/metabolismo , Interleucina-1beta/biossíntese , Interleucina-1beta/líquido cefalorraquidiano , Interleucina-1beta/genética , Camundongos , Camundongos Transgênicos , Neurônios/citologia , Neurotransmissores/biossíntese , Neurotransmissores/líquido cefalorraquidiano , Neurotransmissores/fisiologia , Convulsões/líquido cefalorraquidiano , Convulsões/patologiaRESUMO
New method of qualitative and quantitative analysis of nucleotides in human cerebrospinal fluid (CSF), based on the combination of extraction of purines and pyrimidines to the solid phase (SPE) and high-performance liquid chromatography (HPLC), was proposed. Use of SPE and lyophilization of samples allowed for the first time to detect the presence of di- and triphosphonucleotides in human CSF. Concentration of those compounds varied from 0.003 to 5.0 microM. Differences in the nucleotide mixture composition in human CSF detected with the new method are coupled with the neurological disorders and might be a basis for an efficient diagnostic tool.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Nucleosídeos/líquido cefalorraquidiano , Nucleotídeos/líquido cefalorraquidiano , Epilepsia/líquido cefalorraquidiano , Humanos , Infecções/líquido cefalorraquidiano , Doenças do Sistema Nervoso/líquido cefalorraquidiano , Nucleosídeos/isolamento & purificação , Nucleotídeos/isolamento & purificação , Dor/líquido cefalorraquidiano , Purinas/líquido cefalorraquidiano , Pirimidinas/líquido cefalorraquidiano , Doenças da Coluna Vertebral/líquido cefalorraquidiano , Acidente Vascular Cerebral/líquido cefalorraquidiano , Hemorragia Subaracnóidea/líquido cefalorraquidianoRESUMO
In neurons, 14-3-3 proteins regulate diverse processes, including signal transduction, neurotransmitter production, and apoptosis by binding to target proteins, but the role 14-3-3 proteins play in the pathogenesis of central nervous system (CNS) disease remains unclear. To examine the relationship between presence of 14-3-3 protein in cerebrospinal fluid (CSF) and encephalitis in the SIV/macaque model of HIV CNS disease, CSF levels of 14-3-3 protein were measured by quantitative immunoblotting throughout infection in 6 SIV-infected pigtailed macaques. Beginning during asymptomatic infection and continuing until death, CSF levels of 14-3-3 were elevated in 4 of 6 SIV-infected animals. Animals with 14-3-3 protein in CSF had the highest viral loads in the CSF after acute infection and the highest levels of both viral RNA and protein in brain (p < 0.001). In contrast, the presence of 14-3-3 protein in CSF was not associated with CNS microglial/macrophage activation measured by quantitative immunohistochemical staining for CD68 (p = 0.13). CSF levels of 14-3-3 protein may be a valuable marker of early neuronal damage, CNS viral replication, and CNS disease progression in HIV-infected individuals.
Assuntos
Proteínas 14-3-3/líquido cefalorraquidiano , Doenças do Sistema Nervoso Central/líquido cefalorraquidiano , Síndrome de Imunodeficiência Adquirida dos Símios/líquido cefalorraquidiano , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Astrócitos/metabolismo , Astrócitos/virologia , Axônios/patologia , Axônios/virologia , Gânglios da Base/metabolismo , Gânglios da Base/virologia , Western Blotting/métodos , Células Cultivadas , Doenças do Sistema Nervoso Central/etiologia , Doenças do Sistema Nervoso Central/virologia , Modelos Animais de Doenças , Feto , Produtos do Gene tat/farmacologia , Proteína Glial Fibrilar Ácida/metabolismo , Humanos , Imuno-Histoquímica/métodos , Infecções/líquido cefalorraquidiano , Infecções/complicações , Infecções/virologia , Macaca nemestrina , Macrófagos/metabolismo , Macrófagos/virologia , Microglia/metabolismo , Microglia/virologia , Neurônios/metabolismo , Neurônios/virologia , RNA Mensageiro/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Síndrome de Imunodeficiência Adquirida dos Símios/complicações , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/isolamento & purificação , Vírus da Imunodeficiência Símia/fisiologia , Fatores de Tempo , Proteínas do Envelope Viral/metabolismoRESUMO
Carbonic anhydrase (CA) II is the predominant CA isoenzyme in the brain of mammals. We have recently developed a dual-label time-resolved immunofluorometric assay to quantify minute amounts of CA I and II in the cerebrospinal fluid (CSF). The present study was aimed at elucidating the clinical value of such measurements in the case of neurological disorders. Lumbar CSF samples were obtained from 111 patients suffering from various neurological diseases and from 97 control patients with no specific signs of central nervous system diseases. The highest CA II concentrations were found in patients with brain infarction (median 66.5 micrograms L-1, n = 20), whereas the control patients had markedly lower values (median 7.8 micrograms L-1, n = 97). Relative to a reference range calculated from the control material (10.2 +/- 17.2 micrograms L-1), the sensitivity of CA II measurement in differentiating brain infarction was 100%. Patients with transient ischaemic attack (median 11.2 micrograms L-1, n = 9), multiple sclerosis (median 14.7 micrograms L-1, n = 18) or epilepsy (median 20.3 micrograms L-1, n = 17) usually had CA II concentrations within the normal range, but those with central nervous system infection (n = 14), dementia (n = 19) or trigeminal neuralgia (n = 6) tended to have higher CA II levels in their CSF, the median values being 39.1 micrograms L-1, 45.5 micrograms L-1 and 44.0 micrograms L-1 respectively. The findings indicate that the concentration of CA II in the CSF marks disease activity in patients with brain damage. This finding could provide a basis for further studies estimating the value of CA II measurement as a new laboratory marker of diseases affecting the brain.
Assuntos
Anidrases Carbônicas/líquido cefalorraquidiano , Isoenzimas/líquido cefalorraquidiano , Doenças do Sistema Nervoso/líquido cefalorraquidiano , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Encéfalo/enzimologia , Infarto Cerebral/líquido cefalorraquidiano , Demência/líquido cefalorraquidiano , Epilepsia/líquido cefalorraquidiano , Humanos , Infecções/líquido cefalorraquidiano , Pessoa de Meia-Idade , Valores de Referência , Neuralgia do Trigêmeo/líquido cefalorraquidianoRESUMO
The expression of the costimulatory molecule B7-1 (BB-1; CD80) and its ligand CD28 was investigated on peripheral blood (PB) and cerebrospinal fluid (CSF) T and B lymphocytes and monocytes in 11 patients with relapsing-remitting multiple sclerosis (MS) 21 age-matched healthy controls and 10 patients with central nervous system (CNS) infectious disease (CID). Three channel flow cytometry was used with a novel gating technique in order to unambiguously identify the low numbers of B lymphocytes present in normal CSF. There was a significantly higher fraction of B7-1+ B lymphocytes in the CSF of patients with MS (72%) and CID (69%) when compared with healthy individuals (53%; p < 0.0001 and p < 0.002, respectively). Furthermore, two patients with a clinical picture of encephalitis showed a profoundly increased B7-1 expression on CSF monocytes. Comparison of absolute numbers of B7-1+ B lymphocytes/mL CSF between MS patients and healthy controls revealed a highly increased frequency of these cells among MS patients (235 cells/mL in MS patients versus 3.9 cells/mL in controls; p < 0.0001) with no overlap between the groups, which was otherwise seen for all other analyzed cell populations. We therefore hypothesize that activated B lymphocytes expressing high levels of B7-1 may be of pathogenetic importance in the development and maintenance of the MS disease.
Assuntos
Antígeno B7-1/líquido cefalorraquidiano , Doenças do Sistema Nervoso Central/líquido cefalorraquidiano , Infecções/líquido cefalorraquidiano , Esclerose Múltipla/líquido cefalorraquidiano , Adolescente , Adulto , Idoso , Antígenos/análise , Antígenos/líquido cefalorraquidiano , Linfócitos B/metabolismo , Doenças do Sistema Nervoso Central/imunologia , Líquido Cefalorraquidiano/citologia , Encefalite/líquido cefalorraquidiano , Citometria de Fluxo , Humanos , Infecções/imunologia , Pessoa de Meia-Idade , Monócitos/metabolismo , Esclerose Múltipla/imunologia , Reprodutibilidade dos TestesRESUMO
Plaque-periplaque areas from MS brain tissue were explanted and propagated in tissue culture. The same in vitro techniques that successfully rescued measles virus from SSPE brain, papovavirus from PML brain, and HSV from normal human trigeminal ganglia, were applied. MS brain cells were also inoculated into chimpanzees, multiple rodent species, and embryonated hens eggs. No neurologic disease developed in experimentally infected animals, and no cytopathic effect was observed in explanted cells, or after cocultivation or fusion of MS brain cells with indicator cells. Further analysis of explanted and cocultivated cells by indirect immunofluorescence with various antiviral antisera prepared against viruses associated with post-infectious encephalomyelitis, as well as antisera to other ubiquitous viruses, failed to detect viral antigen. Finally, attempts to detect a latent enveloped virus in MS brain cells by 'superinfecting' MS brain cells in culture with vesicular stomatitis virus (VSV) did not reveal a VSV non-neutralizable fraction. Nevertheless, since oligoclonal bands (OGBs) in the CSF of patients with chronic infectious diseases of the CNS are directed against the causative agent, it is likely that OGBs in MS CSF are antibody directed against the agent or antigen that triggered disease. Although the relevant antibody may be scarce relative to irrelevant antibody in MS CSF, and only small amounts of an MS-specific antigen may be present in brain, this report provides a rationale for strategies proposed in our companion report by Owens et al which will allow detection of an MS-specific antigen or its cognate RNA in brain.
Assuntos
Encéfalo/virologia , Esclerose Múltipla/virologia , Humanos , Imunoglobulina G/líquido cefalorraquidiano , Infecções/líquido cefalorraquidiano , Esclerose Múltipla/epidemiologia , Sistema Nervoso/virologia , PrevalênciaRESUMO
The principal constituent of amyloid plaques found in the brains of individuals with Alzheimer's disease (AD) is a 39-42-amino-acid protein, amyloid beta protein (A beta). This study examined whether the measurement of A beta levels in CSF has diagnostic value. There were 108 subjects enrolled in this prospective study: AD (n = 39), non-AD controls (dementing diseases/syndromes; n = 20), and other (n = 49). CSF was obtained by lumbar puncture, and A beta concentrations were determined using a dual monoclonal antibody immunoradiometric sandwich assay. The mean A beta value for the AD group (15.9 +/- 6.8 ng/ml) was not significantly different from that for the non-AD control group (13.0 +/- 7.1 ng/ml; p = 0.07), and substantial overlap in results were observed. A beta values did not correlate with age (r = -0.05, p = 0.59), severity of cognitive impairment (r = 0.22, p = 0.21), or duration of AD symptoms (r = 0.14, p = 0.45). These findings are in conflict with other reports in the literature; discrepant results could be due to the instability of A beta in CSF. A beta immunoreactivity decays rapidly under certain conditions, particularly multiple freeze/thaw cycles. Use of a stabilizing sample treatment buffer at the time of lumbar puncture allows storage of CSF without loss of A beta reactivity. In conclusion, the total CSF A beta level is not a useful marker for current diagnosis of AD.
Assuntos
Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Proteínas do Líquido Cefalorraquidiano/análise , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/epidemiologia , Doenças Autoimunes/líquido cefalorraquidiano , Biomarcadores , Feminino , Humanos , Infecções/líquido cefalorraquidiano , Inflamação/líquido cefalorraquidiano , Masculino , Transtornos Mentais/líquido cefalorraquidiano , Doenças Metabólicas/líquido cefalorraquidiano , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/líquido cefalorraquidiano , Valor Preditivo dos Testes , Prevalência , Estudos ProspectivosRESUMO
In addition to microbial culture, cytology, and immunological studies, physicians rely on the clinical chemistry laboratory for biochemical analysis of patients' cerebrospinal fluid (CSF). However, apart from routine glucose and protein determinations, the clinical value of other CSF analytes is often unclear. Here, we review the literature pertaining to the use of CSF biochemical measurements in managing patients with infectious disease, neoplasia, stroke and trauma, and dementia. Although a small number of studies demonstrate potential usefulness of some markers, we conclude that, without further study, the data are insufficient to support the routine clinical use of most of the analytes examined.
Assuntos
Líquido Cefalorraquidiano/química , Química Clínica , Neoplasias do Sistema Nervoso Central/líquido cefalorraquidiano , Líquido Cefalorraquidiano/fisiologia , Proteínas do Líquido Cefalorraquidiano/análise , Glucose/líquido cefalorraquidiano , Humanos , Infecções/líquido cefalorraquidiano , Doenças do Sistema Nervoso/líquido cefalorraquidianoAssuntos
Acetilcolinesterase/líquido cefalorraquidiano , Butirilcolinesterase/líquido cefalorraquidiano , Convulsões/enzimologia , Acetilcolinesterase/isolamento & purificação , Adulto , Doenças do Sistema Nervoso Central/líquido cefalorraquidiano , Doenças do Sistema Nervoso Central/enzimologia , Neoplasias do Sistema Nervoso Central/líquido cefalorraquidiano , Neoplasias do Sistema Nervoso Central/enzimologia , Feminino , Humanos , Infecções/líquido cefalorraquidiano , Infecções/enzimologia , Focalização Isoelétrica , Masculino , Meningite , Pessoa de Meia-Idade , Fenitoína/uso terapêutico , Convulsões/líquido cefalorraquidianoRESUMO
Cerebrospinal fluid glucose and cerebrospinal fluid:blood glucose ratios were compared in seven patients with post haemorrhagic hydrocephalus having lumbar puncture/ventricular tap as a therapeutic measure. A control group of 10 babies was used, without intraventricular haemorrhage, and having lumbar puncture as part of a septic screen. Of 50 separate taps in the patient group, 38% had blood glucose measured and 76% had CSF glucose measured. Median cerebrospinal fluid glucose was 1.2 mmol (range, 0.4-2.5 mmol/l) in the patient group and 3.1 mmol/l (range, 1.4-10.3 mmol/l) in the control group. The median cerebrospinal fluid:blood glucose ratio in the patient group was 0.235 (range, 0.07-0.53) and in the control group was 0.709 (range, 0.6-1.4). Hypoglycorrhachia appears to be a normal finding in patients with post haemorrhagic hydrocephalus and does not indicate infection in these infants. Measurement of cerebrospinal fluid:blood glucose ratio is not warranted when cerebrospinal fluid is drained purely as a therapeutic measure in these patients.
Assuntos
Glicemia/metabolismo , Hemorragia Cerebral/complicações , Glucose/líquido cefalorraquidiano , Hidrocefalia/complicações , Infecções , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Infecções/sangue , Infecções/líquido cefalorraquidiano , Valores de ReferênciaRESUMO
Cerebrospinal fluid (CSF) from patients with a variety of central nervous system (CNS) disorders was assayed for cytokines, prostaglandins, and autoantibodies. CSF interleukin-6 (IL-6) in patients with CNS infection (374.24 +/- 92.61 pg/mL) and neuropsychiatric systemic lupus erythematosus (NP-SLE) (71.40 +/- 5.89 pg/mL) were significantly higher than in patients with CNS inflammation (33.92 +/- 29.36 pg/mL) or controls (non-inflammatory CNS diseases) (4.35 +/- 3.00 pg/mL). Interleukin-1 beta, interferon alpha, and tumor necrosis factor alpha were undetectable in these samples: CSF prostaglandin E2 (PGE2) also exhibited similar patterns as IL-6. CSF immunoglobulin G (IgG) in patients with NP-SLE (8.84 +/- 1.80 mg/dL) was much higher than in patients with CNS infection (4.65 +/- 3.09 mg/dL), CNS inflammation (2.54 +/- 1.24 mg/dL), or controls (2.11 +/- 1.03 mg/dL). CSF autoantibodies against calf thymus antigens were present in patients with NP-SLE but not in patients with CNS infection as demonstrated by immunoblot. These results suggest that high IL-6 and PGE2 in CSF favors the diagnosis of CNS infection, while modestly elevated IL-6, high IgG, and autoantibodies against calf thymus antigens in CSF are the features of NP-SLE.