RESUMO
BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is a common disorder that is accompanied by structural brain changes. This meta-analysis aimed to evaluate the effect of OSAS on the serum levels of astrocytic protein (S100B) and neuron-specific enolase (NSE) in observational studies. METHODS: A comprehensive search was performed in the PubMed/Medline, Web of Science, Scopus, ScienceDirect, and Cochrane Library databases to assess the serum level of S100B and/or NSE in patients with OSAS and/or controls. The quality of the study was evaluated by the Newcastle-Ottawa Scale (NOS). A random-effects model was performed using RevMan 5.3 with the mean difference (MD) and 95% confidence intervals (CIs). RESULTS: Out of 63 studies found in the mentioned databases and one identified by a manual search, nine studies were included and analyzed in this meta-analysis (three cross-sectional and six case-control studies). The analysis showed that the S100B [MD = 53.58 pg/ml, 95%CI: 1.81, 105.35; P = 0.04] and NSE levels [MD = 3.78 ng/ml, 95%CI: 2.07, 5.48; P < 0.0001] were significantly higher in patients than the controls. However, there were no significant differences between the S100B [MD = -28.00 pg/ml, 95%CI: - 79.48, 23.47; P = 0.29] and NSE levels [MD = 0.49 ng/ml, 95%CI: - 0.82, 1.80; P = 0.46]. CONCLUSIONS: This meta-analysis found elevated serum S100B and NSE levels in OSAS patients compared to the controls, which suggests that these markers may be used as peripheral indicators of brain damage in OSAS.
Assuntos
Dano Encefálico Crônico/sangue , Fosfopiruvato Hidratase/sangue , Subunidade beta da Proteína Ligante de Cálcio S100/sangue , Apneia Obstrutiva do Sono/sangue , Biomarcadores/sangue , Humanos , Estudos Observacionais como AssuntoRESUMO
Objectives- The prediction of patients at risk for poor clinical outcome after acute ischemic stroke remains challenging. An imbalance of coagulation factors may play an important role in progression and prognosis of these patients. In this systematic review, we assessed the current literature on hemostasis biomarkers and the association with poor clinical outcome in acute ischemic stroke. Approach and Results- A systematic search of Embase, Medline, Cochrane Library, Web of Science, and Google Scholar was performed on studies reporting on hemostasis biomarkers and clinical outcome after acute ischemic stroke. Studies were considered eligible if blood samples were collected within 72 hours after symptom onset. Additionally, clinical outcome should be assessed using a disability score (Barthel Index or modified Rankin scale). Methodological quality of included studies was assessed with an adapted version of the Quality Assessment of Diagnostic Accuracy Studies questionnaire. A total of 80 articles were read full text, and 41 studies were considered eligible for inclusion, reporting on 37 different hemostasis biomarkers. No single biomarker appeared to be effective in predicting poor clinical outcome in acute ischemic stroke patients. Conclusions- Based on current literature, no clear recommendations can be provided on which hemostasis biomarkers are a predictor of clinical outcome after acute ischemic stroke. However, some biomarkers show promising results and need to be further investigated and validated in large populations with clear defined study designs.
Assuntos
Biomarcadores/sangue , Isquemia Encefálica/sangue , Hemostasia , Doença Aguda , Anticorpos Antifosfolipídeos/sangue , Proteínas Sanguíneas/análise , Dano Encefálico Crônico/sangue , Dano Encefálico Crônico/etiologia , Isquemia Encefálica/complicações , Estudos de Casos e Controles , Ensaios Clínicos como Assunto , Estudos de Coortes , Avaliação da Deficiência , Humanos , Inibidor de Coagulação do Lúpus/sangue , Prognóstico , Reprodutibilidade dos Testes , Resultado do TratamentoRESUMO
OBJECTIVES: According to aquaporin-4 antibody (AQP4-Ab), neuromyelitis optica (NMO) can be divided into seropositive and seronegative subgroups. The purpose of this study was to a) compare the distribution of spinal cord and brain magnetic resonance imaging (MRI) lesions between seropositive and seronegative NMO patients; b) explore occult brain damage in seropositive and seronegative NMO patients; and c) explore the contribution of visible lesions to occult grey and white matter damage in seropositive and seronegative NMO patients. MATERIALS AND METHODS: Twenty-two AQP4-Ab seropositive and 14 seronegative NMO patients and 30 healthy controls were included in the study. Two neuroradiologists independently measured the brain lesion volume (BLV) and the length of spinal cord lesion (LSCL) and recorded the region of brain lesions. The normal-appearing grey matter volume (NAGM-GMV) and white matter fractional anisotropy (NAWM-FA) were calculated for each subject to evaluate occult brain damage. RESULTS: The seropositive patients displayed more extensive damage in the spinal cord than the seronegative patients, and the seronegative group had a higher proportion of patients with brainstem lesions (28.57%) than the seropositive group (4.55%, P=0.064). Both NMO subgroups exhibited reduced NAGM-GMV and NAWM-FA compared with the healthy controls. NAGM-GMV was negatively correlated with LSCL in the seropositive group (rs=-0.444, P=0.044) and with BLV in the seronegative group (rs=-0.768, P=0.002). NAWM-FA was also negatively correlated with BLV in the seropositive group (rs=-0.682, P<0.001). CONCLUSION: Our findings suggest that the occult brain damage in these two NMO subgroups may be due to different mechanisms, which need to be further clarified.
Assuntos
Dano Encefálico Crônico/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Neuromielite Óptica/diagnóstico por imagem , Medula Espinal/diagnóstico por imagem , Encéfalo/patologia , Dano Encefálico Crônico/sangue , Dano Encefálico Crônico/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuromielite Óptica/complicações , Neuromielite Óptica/patologia , Medula Espinal/patologiaRESUMO
OBJECTIVE: Our aim was to explore the association between plasma cytokines and febrile status epilepticus (FSE) in children, as well as their potential as biomarkers of acute hippocampal injury. METHODS: Analysis was performed on residual samples of children with FSE (n = 33) as part of the Consequences of Prolonged Febrile Seizures in Childhood study (FEBSTAT) and compared to children with fever (n = 17). Magnetic resonance imaging (MRI) was obtained as part of FEBSTAT within 72 h of FSE. Cytokine levels and ratios of antiinflammatory versus proinflammatory cytokines in children with and without hippocampal T2 hyperintensity were assessed as biomarkers of acute hippocampal injury after FSE. RESULTS: Levels of interleukin (IL)-8 and epidermal growth factor (EGF) were significantly elevated after FSE in comparison to controls. IL-1ß levels trended higher and IL-1RA trended lower following FSE, but did not reach statistical significance. Children with FSE were found to have significantly lower ratios of IL-1RA/IL-1ß and IL-1RA/IL-8. Specific levels of any one individual cytokine were not associated with FSE. However, lower ratios of IL-1RA/IL-1ß, IL-1RA/1L-6, and IL-1RA/ IL-8 were all associated with FSE. IL-6 and IL-8 levels were significantly higher and ratios of IL-1RA/IL-6 and IL-1RA/IL-8 were significantly lower in children with T2 hippocampal hyperintensity on MRI after FSE in comparison to those without hippocampal signal abnormalities. Neither individual cytokine levels nor ratios of IL-1RA/IL-1ß or IL-1RA/IL-8 were predictive of MRI changes. However, a lower ratio of IL-1RA/IL-6 was strongly predictive (odds ratio [OR] 21.5, 95% confidence interval [CI] 1.17-393) of hippocampal T2 hyperintensity after FSE. SIGNIFICANCE: Our data support involvement of the IL-1 cytokine system, IL-6, and IL-8 in FSE in children. The identification of the IL-1RA/IL-6 ratio as a potential biomarker of acute hippocampal injury following FSE is the most significant finding. If replicated in another study, the IL-1RA/IL-6 ratio could represent a serologic biomarker that offers rapid identification of patients at risk for ultimately developing mesial temporal lobe epilepsy (MTLE).
Assuntos
Biomarcadores/sangue , Dano Encefálico Crônico/sangue , Citocinas/sangue , Hipocampo/diagnóstico por imagem , Hipocampo/fisiopatologia , Convulsões Febris/sangue , Estado Epiléptico/sangue , Dano Encefálico Crônico/diagnóstico por imagem , Criança , Pré-Escolar , Epilepsia do Lobo Temporal/sangue , Feminino , Humanos , Lactente , Recém-Nascido , Proteína Antagonista do Receptor de Interleucina 1/sangue , Interleucina-1beta/sangue , Interleucina-6/sangue , Interleucina-8/sangue , Masculino , Fatores de Risco , Convulsões Febris/diagnóstico por imagem , Estado Epiléptico/diagnóstico por imagemRESUMO
Neurophysiological and neurological dysfunction is usually experienced for a short period of time in patients with mild traumatic brain injury (mTBI). However, around 15 % of patients exhibit symptoms months after TBI. Phospholipid (PL) changes have been observed in plasma from mTBI patients at chronic stages, suggesting a role in TBI pathology. We examined long-term plasma phospholipid profiles in a mouse model of mTBI to determine their translational value in reproducing PL changes observed in mTBI patients. Plasma samples were collected at an acute timepoint (24 h post-injury) and at several chronic stages (3, 6, 12 and 24 months post-injury) from injured mice and sham controls. Phospholipids were identified and quantified using liquid chromatography/mass spectrometry analysis. In accordance with human data, we observed significantly lower levels of several major PL classes in mTBI mice compared to controls at chronic timepoints. Saturated, monounsaturated and polyunsaturated fatty acids (PUFAs) were differently regulated over time. As PUFA levels were decreased at 3 months, we measured levels of malondialdehyde to assess lipid peroxidation, which we found to be elevated at this timepoint. Ether-containing PE species were elevated at 24 h post-injury and decreased relative to controls at chronic stages. Arachidonic acid and docosahexaenoic acid-containing species were significantly decreased within all PL classes at the chronic stages. Our findings are similar to changes in PL levels observed in human mTBI subjects. Chronic TBI biomarkers have received little attention, even though disabilities at this stage can be of major importance. Our study provides information on biochemical abnormalities that persist long after the initial injury; these abnormalities may provide useful insight into the continuing pathogenesis and serve as diagnostic biomarkers.
Assuntos
Dano Encefálico Crônico/sangue , Lesões Encefálicas Traumáticas/sangue , Fosfolipídeos/sangue , Animais , Ácidos Araquidônicos/sangue , Biomarcadores , Encéfalo/metabolismo , Dano Encefálico Crônico/etiologia , Lesões Encefálicas Traumáticas/complicações , Ácidos Docosa-Hexaenoicos/sangue , Inflamação , Peroxidação de Lipídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Peroxissomos/metabolismo , Distribuição Aleatória , Fatores de TempoRESUMO
BACKGROUND AND PURPOSE: Brain-derived neurotrophic factor (BDNF) plays important roles in brain plasticity and repair, and it influences stroke outcomes in animal models. Circulating BDNF concentrations are lowered in patients with traumatic brain injury, and low BDNF predicts poor recovery after this injury. We sought to investigate whether circulating concentrations of BDNF are altered in the acute phase of ischemic stroke and whether they are associated with short- or long-term functional outcome. METHODS: Serum concentrations of BDNF were measured in the Sahlgrenska Academy Study on Ischemic Stroke. The main outcomes were modified Rankin Scale (mRS) good (mRS score of 0-2) versus poor (mRS score of 3-6) at 3 months and 2 years after stroke, and good (mRS score of 0-2) versus poor (mRS score of 3-5) at 7 years after stroke. RESULTS: Acute concentrations of BDNF were significantly lower in ischemic stroke cases (n=491) compared with controls (n=513). BDNF concentrations were not significantly associated with 3-month outcome. However, patients with BDNF in the lowest tertile had an increased risk of experiencing a poor outcome both at 2-year and 7-year follow-up, and these associations were independent of vascular risk factors and stroke severity (odds ratio, 2.6; confidence intervals, 1.4-4.9; P=0.002 and odds ratio, 2.1; confidence intervals, 1.1-3.9; P=0.028, respectively). CONCLUSIONS: Circulating concentrations of BDNF protein are lowered in the acute phase of ischemic stroke, and low levels are associated with poor long-term functional outcome. Further studies are necessary to confirm these associations and to determine the predictive value of BDNF in stroke outcomes.
Assuntos
Isquemia Encefálica/sangue , Fator Neurotrófico Derivado do Encéfalo/sangue , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/epidemiologia , Biomarcadores/sangue , Dano Encefálico Crônico/sangue , Dano Encefálico Crônico/etiologia , Isquemia Encefálica/terapia , Comorbidade , Diabetes Mellitus/epidemiologia , Feminino , Seguimentos , Humanos , Hiperlipidemias/epidemiologia , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Modelos Cardiovasculares , Curva ROC , Recuperação de Função Fisiológica , Fatores de Risco , Fatores Sexuais , Fumar/epidemiologia , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: Neuropsychiatric (NP) lupus, a common manifestation of systemic lupus erythematosus (SLE), is still insufficiently understood, in part, because of the lack of specific biomarkers. Neuron specific enolase (NSE), an important neuronal glycolytic enzyme, shows increased serum levels following acute brain injury, and decreased serum levels in several chronic disorders of the nervous system, including multi infarct dementia, multiple sclerosis and depression. The aim of the study was to evaluate serum NSE levels in SLE patients with and without nervous system involvement, and in healthy controls, and to assess the correlation of NSE serum levels of patients with neuropsychiatric systemic lupus erythematosus (NPSLE) with clinical parameters. METHODS: The study comprised 47 SLE patients and 28 controls. SLE activity was assessed using the Systemic Lupus Activity Measure (SLAM). A neurologist and a psychiatrist examined all patients. NP involvement was diagnosed according to strict NPSLE criteria proposed by Ainiala and coworkers, as modification to American College of Rheumatology (ACR) nomenclature and case definitions. NSE serum levels were determined by use of an immunoassay. RESULTS: Mean NSE serum concentrations in patients with NPSLE were significantly lower than in non-NPSLE patients (6.3 ± 2.6 µg/L vs. 9.7 ± 3.3 µg/L, p < 0.01) and in controls (8.8 ± 3.3 µg/L, p < 0.05). There were significant negative correlations between NSE serum levels and SLE activity (r = -0.42, p < 0.05) and the number of NPSLE manifestations diagnosed (-0.37; p = 0.001). CONCLUSION: Decreased serum concentrations of NSE may reflect chronic neuronal damage with declined metabolism of the nervous tissue in patients with NPSLE.
Assuntos
Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/psicologia , Fosfopiruvato Hidratase/sangue , Adulto , Idoso , Biomarcadores/sangue , Dano Encefálico Crônico/sangue , Estudos de Casos e Controles , Feminino , Humanos , Vasculite Associada ao Lúpus do Sistema Nervoso Central/sangue , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Masculino , Transtornos Mentais/sangue , Transtornos Mentais/líquido cefalorraquidiano , Transtornos Mentais/etiologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Adulto JovemRESUMO
The onset of hyperammonemia due to the flow of ammonia-rich portal vein blood through a portal-systemic shunt causes a type of encephalopathy known as chronic portal-systemic shunt encephalopathy (CPSE). We herein report two cases of CPSE that presented with opposite changes in the blood ammonia concentrations during hemodialysis. It is curious that the encephalopathy was ameliorated by hemodialysis in case 1, but not case 2. Therefore, it is necessary to recognize CPSE and assess the blood ammonia concentrations in dialysis patients who develop a disturbance of consciousness, even if the serum transaminase level is normal.
Assuntos
Amônia/sangue , Dano Encefálico Crônico/sangue , Dano Encefálico Crônico/etiologia , Diálise Renal/efeitos adversos , Idoso , Dano Encefálico Crônico/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Veia Porta , Resultado do TratamentoRESUMO
BACKGROUND: Data regarding immunomodulatory effects of parenteral n-3 fatty acids in sepsis are conflicting. In this study, the effect of administration of parenteral n-3 fatty acids on markers of brain injury, incidence of sepsis-associated delirium, and inflammatory mediators in septic patients was investigated. METHODS: Fifty patients with sepsis were randomized to receive either 2 ml/kg/day of a lipid emulsion containing highly refined fish oil (equivalent to n-3 fatty acids 0.12 mg/kg/day) during 7 days after admission to the intensive care unit or standard treatment. Markers of brain injury and inflammatory mediators were measured on days 1, 2, 3 and 7. Assessment for sepsis-associated delirium was performed daily. The primary outcome was the difference in S-100ß from baseline to peak level between both the intervention and the control group, compared by t-test. Changes of all markers over time were explored in both groups, fitting a generalized estimating equations model. RESULTS: Mean difference in change of S-100ß from baseline to peak level was 0.34 (95% CI: -0.18-0.85) between the intervention and control group, respectively (P = 0.19). We found no difference in plasma levels of S-100ß, neuron-specific enolase, interleukin (IL)-6, IL-8, IL-10, and C-reactive protein between groups over time. Incidence of sepsis-associated delirium was 75% in the intervention and 71% in the control groups (risk difference 4%, 95% CI -24-31%, P = 0.796). CONCLUSION: Administration of n-3 fatty acids did not affect markers of brain injury, incidence of sepsis-associated delirium, and inflammatory mediators in septic patients.
Assuntos
Dano Encefálico Crônico/prevenção & controle , Delírio/prevenção & controle , Ácidos Graxos Ômega-3/uso terapêutico , Óleos de Peixe/uso terapêutico , Sepse/complicações , Idoso , Biomarcadores , Dano Encefálico Crônico/sangue , Dano Encefálico Crônico/etiologia , Proteína C-Reativa/análise , Delírio/sangue , Delírio/etiologia , Emulsões , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-3/efeitos adversos , Ácidos Graxos Ômega-3/farmacologia , Feminino , Óleos de Peixe/administração & dosagem , Óleos de Peixe/efeitos adversos , Óleos de Peixe/farmacologia , Seguimentos , Humanos , Hipertrigliceridemia/induzido quimicamente , Mediadores da Inflamação/sangue , Interleucinas/sangue , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Fosfopiruvato Hidratase/sangue , Subunidade beta da Proteína Ligante de Cálcio S100/sangue , Sepse/sangueRESUMO
PURPOSE OF REVIEW: Early prognostication in acute brain damage remains a challenge in the realm of critical care. There remains controversy over the most optimal methods that can be utilized to predict outcome. The utility of recently reported prognostic biomarkers and clinical methods will be reviewed. RECENT FINDINGS: Recent guidelines touch upon prognostication techniques as part of management recommendations. In addition to novel laboratory values, there have been few reports on the use of clinical parameters, diagnostic imaging techniques, and electrophysiological techniques to assist in prognostication. SUMMARY: Although encouraging, newer markers are not capable of providing accurate estimates on outcomes in acute injuries of the central nervous system. Traditional markers of prognostication may not be applicable in the light of newer and effective therapies (i.e. hypothermia). Substantial research in the field of outcome determination is in progress, but these studies need to be interpreted with caution.
Assuntos
Dano Encefálico Crônico/sangue , Lesões Encefálicas/sangue , Cuidados Críticos , Eletrofisiologia/métodos , Parada Cardíaca/sangue , Neuroimagem/métodos , Biomarcadores/sangue , Dano Encefálico Crônico/mortalidade , Dano Encefálico Crônico/fisiopatologia , Lesões Encefálicas/mortalidade , Lesões Encefálicas/fisiopatologia , Proteína C-Reativa/metabolismo , Tomada de Decisões , Medicina Baseada em Evidências , Potenciais Somatossensoriais Evocados , Família , Feminino , Parada Cardíaca/mortalidade , Parada Cardíaca/fisiopatologia , Humanos , Hipotermia Induzida , Masculino , Atividade Motora , Proteínas de Neoplasias/sangue , Fatores de Crescimento Neural/sangue , Guias de Prática Clínica como Assunto , Prognóstico , Ordens quanto à Conduta (Ética Médica) , Subunidade beta da Proteína Ligante de Cálcio S100 , Proteínas S100/sangue , Componente Amiloide P Sérico/metabolismoRESUMO
OBJECTIVES: The aim of this study was to determine the added value of the serum biomarkers S100 and neuron-specific enolase to clinical characteristics for predicting outcome after out-of-hospital cardiac arrest. BACKGROUND: Serum S100 beta (S100B) and neuron-specific enolase concentrations rise after brain injury. METHODS: A prolective observational study was conducted among all adult survivors of nontraumatic out-of-hospital cardiac arrest admitted to 1 hospital (April 3, 2008 to April 3, 2011). Three blood samples (on arrival and on days 1 and 3) were drawn for biomarkers, contingent on survival. Follow-up continued until in-hospital death or discharge. Outcomes were defined as good (Cerebral Performance Category score 1 or 2) or poor (Cerebral performance category score 3 to 5). RESULTS: A total of 195 patients were included (65.6% men, mean age 73 ± 16 years), with presenting rhythms of asystole in 61.5% and ventricular tachycardia or ventricular fibrillation in 24.1%. Only 43 patients (22.0%) survived to hospital discharge, 26 (13.3%) with good outcomes. Patients with good outcomes had significantly lower S100B levels at all time points and lower neuron-specific enolase levels on days 1 and 3 compared with those with poor outcomes. Independent predictors at admission of a good outcome were younger age, a presenting rhythm of ventricular tachycardia or ventricular fibrillation, and lower S100B level. Predictors on day 3 were younger age and lower day 3 S100B level. The area under the receiver-operating characteristic curve of the admission-day model was 0.932 with and 0.880 without biomarker data (p = 0.027 for the difference). CONCLUSIONS: Risk stratification after out-of-hospital cardiac arrest using both clinical and biomarker data is feasible. The biomarkers, although adding an ostensibly modest 5.2% to the area under the receiver-operating characteristic curve, substantially reduced the level of uncertainty in decision making. Nevertheless, current biomarkers cannot replace societal considerations in determining acceptable levels of uncertainty. (Protein S100 Beta as a Predictor of Resuscitation Outcome; NCT00814814).
Assuntos
Técnicas de Apoio para a Decisão , Fatores de Crescimento Neural/sangue , Parada Cardíaca Extra-Hospitalar/sangue , Fosfopiruvato Hidratase/sangue , Proteínas S100/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Dano Encefálico Crônico/sangue , Dano Encefálico Crônico/mortalidade , Feminino , Humanos , Israel , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Parada Cardíaca Extra-Hospitalar/mortalidade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Curva ROC , Ressuscitação , Subunidade beta da Proteína Ligante de Cálcio S100RESUMO
OBJECTIVES: The purpose of this study was to investigate neuropeptides in patients presenting with symptoms of acute cerebrovascular disease. BACKGROUND: The precursor neuropeptides proenkephalin A (PENK-A) and protachykinin (PTA) are markers of blood-brain barrier integrity and have been recently discussed in vascular dementia and neuroinflammatory disorders. METHODS: In a prospective observational study, we measured plasma PENK-A and PTA concentrations in 189 consecutive patients who were admitted with symptoms of acute stroke. Plasma concentrations were determined by sandwich immunoassay; lower detection limits were 15.6 pmol/l (PENK-A) and 22 pmol/l (PTA). Clinical outcome was assessed at 3 months for mortality, major adverse cerebro/cardiovascular events, and functional outcome (modified Rankin scale). RESULTS: PENK-A was significantly elevated in patients with ischemic stroke (n = 124; 65.6%) compared to patients with transient ischemic attack (n = 16; 8.5%) and to patients with nonischemic events (n = 49; 25.9%): median (interquartile range), stroke 123.8 pmol/l (93 to 160.5); transient ischemic attack 114.5 pmol/l (85.3 to 138.8); and nonischemic event 102.8 pmol/l (76.4 to 137.6; both groups vs. stroke p < 0.05). High concentrations of PENK-A, but not PTA, were related to severity of stroke as assessed by National Institutes of Health Stroke Scale (NIHSS [r = 0.225; p = 0.002]) and to advanced functional disability (modified Rankin Scale score 3 to 6 vs. 0 to 2: 135.1 pmol/l [99.2 to 174.1] vs. 108.9 pmol/l [88.6 to 139.5]; p = 0.014). After adjusting for age, NIHSS, and brain lesion size (computed tomography), PENK-A predicted mortality (hazard ratio [HR] for log-10 PENK-A in pmol/l: 4.52; 95% confidence interval [CI]: 1.1 to 19.0; p < 0.05) and major adverse cerebro/cardiovascular events (HR: 6.65; 95% CI: 1.8 to 24.9; p < 0.05). Patients in the highest quartile of PENK-A (cutoff >153 pmol/l) had an increased risk of mortality (HR: 2.40; 95% CI: 1.02 to 5.40; p < 0.05) and of major adverse cerebro/cardiovascular events (HR: 2.23; 95% CI: 1.10 to 4.54; p < 0.05). CONCLUSIONS: PENK-A is a prognostic biomarker in the acute phase of ischemic stroke. Elevated PENK-A concentrations are associated with ischemic stroke, severity of cerebral injury, and may have prognostic value for fatal and nonfatal events.
Assuntos
Biomarcadores/sangue , Dano Encefálico Crônico/sangue , Dano Encefálico Crônico/mortalidade , Isquemia Encefálica/sangue , Isquemia Encefálica/mortalidade , Infarto Cerebral/sangue , Infarto Cerebral/mortalidade , Encefalinas/sangue , Precursores de Proteínas/sangue , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Avaliação da Deficiência , Feminino , Seguimentos , Humanos , Arteriosclerose Intracraniana/sangue , Arteriosclerose Intracraniana/mortalidade , Ataque Isquêmico Transitório/sangue , Ataque Isquêmico Transitório/mortalidade , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Taquicininas/sangueRESUMO
OBJECTIVE: To evaluate if type 2 diabetes mellitus (DM) constitutes a prognostic factor for death and severe disability in patients with aneurysm clipping after subarachnoid hemorrhage (ASH), in an Intensive Care Unit (ICU). MATERIAL AND METHODS: This is a cohort study in patients who were admitted to the ICU between December-2009 and June-2010; 20 with DM (exposed group) and 40 without DM (non-exposed group). Mortality was quantified during ICU stay. At ICU discharge, severe disability was measured through the Glasgow Outcome Scale (category 2); and Glasgow Coma Scale was used to estimate the difference in consciousness level between ICU arrival and discharge. Descriptive statistics and Kaplan Meier survival curves were performed. RESULTS: Mean age was similar between groups (55.8 +/- 11 and 55.6 +/- 15 years, respectively, p = 0.40). A vegetative state was present in one patient without DM. The Glasgow Coma Scale score at ICU entry was 14.1 +/- 1.4 and at discharge, 12.0 +/- 3.6 in the exposed group (p = 0.01); and 13.9 +/- 2.0 us. 13.5 +/- 2.6, in the non-exposed group, respectively (p = 0.45). There were 3 deaths in patients with DM and 5, in patients without DM (p > 0.05); survival time was 12 (95%CI 7, 16) and 10 days (95%CI 7, 13), respectively. Mean glucose remained higher in patients who died at the ICU (p < 0.001). Hydrocephaly was present in 6 exposed patients and 2, non-exposed (p = 0.007). Additionally, 7 and 5 with and without DM, respectively registered a positive blood culture (p = 0.04). CONCLUSIONS: DM was not associated with higher mortality in ICU patients, but hyperglycemia was; thus, it is essential that the intensive care provider watches closely the glycemic control.
Assuntos
Diabetes Mellitus Tipo 2/complicações , Mortalidade Hospitalar , Aneurisma Intracraniano/cirurgia , Hemorragia Subaracnóidea/cirurgia , Idoso , Bacteriemia/complicações , Bacteriemia/epidemiologia , Glicemia/análise , Dano Encefálico Crônico/sangue , Dano Encefálico Crônico/epidemiologia , Dano Encefálico Crônico/etiologia , Estudos de Coortes , Diabetes Mellitus Tipo 2/sangue , Feminino , Escala de Coma de Glasgow , Humanos , Hidrocefalia/sangue , Hidrocefalia/epidemiologia , Hidrocefalia/etiologia , Hiperglicemia/epidemiologia , Hiperglicemia/etiologia , Unidades de Terapia Intensiva/estatística & dados numéricos , Aneurisma Intracraniano/sangue , Aneurisma Intracraniano/complicações , Estimativa de Kaplan-Meier , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estado Vegetativo Persistente/sangue , Estado Vegetativo Persistente/epidemiologia , Estado Vegetativo Persistente/etiologia , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Prognóstico , Estudos Retrospectivos , Hemorragia Subaracnóidea/sangue , Hemorragia Subaracnóidea/complicaçõesRESUMO
OBJECTIVE: To evaluate the hypothesis that elevated levels of inflammation-related proteins in early postnatal blood predict impaired mental and motor development in extremely preterm infants. STUDY DESIGN: We measured concentrations of 25 inflammation-related proteins in blood collected on postnatal days 1, 7, and 14 from 939 infants born before 28 weeks gestation. An elevated level was defined as a concentration in the highest quartile for gestational age and day of blood collection. We identified impaired development at age 24 months using the Bayley Scales of Infant Development, Second Edition. The primary outcomes were scores on the Mental Scale or the Motor Scale of <55 (more than 3 SDs below the mean). RESULTS: For 17 of the 25 inflammation-related proteins, 1 or more statistically significant associations (P<.01) was found between an elevated blood level of the protein and a developmental impairment. Elevations on multiple days were more often associated with developmental impairment than were elevations present for only 1 day. The highest number of predictive elevations was found in day-14 blood. CONCLUSION: In extremely preterm infants, elevated levels of inflammation-related proteins in blood collected on postnatal days 7 and 14, especially when sustained, are associated with impaired mental and motor development at age 2 years.
Assuntos
Proteínas Sanguíneas/análise , Dano Encefálico Crônico/sangue , Deficiências do Desenvolvimento/etiologia , Idade Gestacional , Doenças do Prematuro/sangue , Dano Encefálico Crônico/complicações , Desenvolvimento Infantil , Pré-Escolar , Deficiências do Desenvolvimento/diagnóstico , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Inflamação , Fatores de RiscoRESUMO
Traumatic brain injury (TBI) is a major cause of morbidity and mortality, and early predictors of neurological outcomes are of great clinical importance. Cell free DNA (CFD), a biomarker used for the diagnosis and monitoring of several diseases, has been implicated as a possible prognostic indicator after TBI. The purpose of this study was to determine the pattern and timing of CFD levels after TBI, and whether a relationship exists between the level of CFD and brain edema and neurological outcomes. Thirty-nine Sprague-Dawley rats were randomly assigned to two groups: rats in group 1 (sham group) were anesthetized and had a scalp incision without TBI, and rats in group 2 were anesthetized and had a scalp incision with TBI, which was induced by using a weight drop model that causes diffuse brain injury. A neurological severity score (NSS) was assessed at 1, 24, and 48 h after TBI. CFD was measured via blood samples drawn at t=0 (baseline), 12, 24, 48, 72, and 120 h after TBI. At 48 h after TBI, brain edema was determined in a subgroup of 11 rats by calculating the difference between rats' wet and dry brain weight. The significance of comparisons between and within groups (CFD levels, brain water content, and NSS) were determined using the Kruskal-Wallis, Mann-Whitney and Student t test. The correlation between CFD levels and the NSS, as well as between CFD levels and the extent of brain edema, was calculated using the Spearman and Pearson tests, respectively. Compared with baseline levels, the CFD levels in rats subjected to TBI were significantly increased at 24 and 48 h after TBI (p<0.01 and p<0.05, respectively). A positive correlation was demonstrated between CFD levels 24 h following TBI and the extent of brain edema (r=0.63, p<0.05), as well as between CFD levels and the NSS (r=0.79, p<0.005). In this study, we demonstrated an increase in CFD levels after TBI, as well as a correlation between CFD levels and brain edema and NSS. CFD levels may provide a quick, reliable, and simple prognostic indicator of neurological outcome in animals after TBI. Its role in humans has not been clearly elucidated, but has potentially significant clinical implications.
Assuntos
Dano Encefálico Crônico/sangue , Edema Encefálico/sangue , Lesões Encefálicas/sangue , DNA/sangue , Animais , Biomarcadores/sangue , Dano Encefálico Crônico/diagnóstico , Dano Encefálico Crônico/patologia , Edema Encefálico/diagnóstico , Edema Encefálico/patologia , Lesões Encefálicas/diagnóstico , Lesões Encefálicas/patologia , Sistema Livre de Células/metabolismo , Sistema Livre de Células/patologia , Modelos Animais de Doenças , Masculino , Valor Preditivo dos Testes , Ratos , Ratos Sprague-DawleyRESUMO
Levels of antibodies AB (AB) to S100B and S100B protein were studied in the blood serum of children with different severity and outcomes of traumatic brain injury (TBI) from the 1st to 15-75th days after TBI. Severity and outcomes were assessed using the Glasgow Coma Scale (GCS). Patients were stratified by outcomes into the following groups: complete recovery (group 1), moderate disability (group 2), high disability (group 3), vegetative state (group 4) and fatal outcome (group 5). In patients of groups 1-3, the changes of S100B in the blood serum didn't depend on the severity of brain's damage; the significant increase of S100B protein levels in the 1st day was accompanied by the decrease to the normal range in the following 2-3 days. On the contrary, the levels of nAB in these groups increased starting from 3-5 days corresponding to the severity of brain's damage. The development of vegetative state was accompanied by low S100B and high AB to S100B levels in the blood serum. The maximal level of S100B protein and increased levels of AB were observed in patients with fatal outcome. In most patients with combined TBI, the levels of both parameters were higher compared to those with separate TBI.
Assuntos
Autoanticorpos/sangue , Dano Encefálico Crônico/diagnóstico , Lesões Encefálicas/diagnóstico , Fatores de Crescimento Neural/sangue , Proteínas S100/sangue , Biomarcadores/sangue , Dano Encefálico Crônico/sangue , Lesões Encefálicas/sangue , Criança , Escala de Coma de Glasgow , Humanos , Fatores de Crescimento Neural/imunologia , Subunidade beta da Proteína Ligante de Cálcio S100 , Proteínas S100/imunologiaRESUMO
Prematurity apnea remains a major clinical problem that requires treatment choices which are sometimes difficult. Prematurity apnea occurs in most infants of gestational age at birth less than 33 weeks. It is a developmental disorder which usually reflects a "physiological" immaturity of respiratory control. However, neonatal diseases may be associated and play an additive role, resulting in an increased incidence of apnea. Careful screening should therefore be performed in order to make sure that no other factor than immaturity is involved in the occurrence of apnea. Short apnea (less than 10s, without hypoxemia and bradycardia), due to immaturity, are not clinically relevant. More prolonged apnea, that last for more than 15 or 20s, and / or apnea associated with bradycardia or oxygen desaturation, results in short-term disturbances of cerebral haemodynamics and oxygenation, which may negatively impact on neurodevelopmental outcome. Evaluating the immediate severity of apnea and the risks that apnea may affect long-term outcome remains a challenge. The choice of treatments is based on a few evidences. Caffeine citrate, which reduces the incidence of apnea, has been used for decades. However, a thorough evaluation of risks and benefits of this medication has been performed only recently. Caffeine citrate was found to be safe and resulted in unexpected benefits. In treated infants, compared with controls, indeed, a decreased incidence of the following complications was recorded: bronchopulmonary dysplasia at 36 weeks of conceptional age, patent ductus arteriosus, cerebral palsy at 18 months of age. Nasal CPAP can be used in association with caffeine citrate, when the latter is not effective enough.
Assuntos
Apneia/etiologia , Doenças do Prematuro/etiologia , Apneia/sangue , Apneia/tratamento farmacológico , Bradicardia/sangue , Bradicardia/etiologia , Dano Encefálico Crônico/sangue , Dano Encefálico Crônico/prevenção & controle , Displasia Broncopulmonar/sangue , Displasia Broncopulmonar/prevenção & controle , Cafeína/efeitos adversos , Cafeína/uso terapêutico , Estimulantes do Sistema Nervoso Central/efeitos adversos , Estimulantes do Sistema Nervoso Central/uso terapêutico , Citratos/efeitos adversos , Citratos/uso terapêutico , Terapia Combinada , Pressão Positiva Contínua nas Vias Aéreas , Idade Gestacional , Humanos , Recém-Nascido , Doenças do Prematuro/sangue , Doenças do Prematuro/tratamento farmacológico , Triagem Neonatal , Oxigênio/sangue , Fatores de RiscoRESUMO
CONTEXT: Severe neonatal hyperbilirubinemia is associated with chronic bilirubin encephalopathy (kernicterus). OBJECTIVE: To systematically review the effectiveness of specific screening modalities to prevent neonatal bilirubin encephalopathy. METHODS: We identified studies through Medline searches, perusing reference lists and by consulting with US Preventive Services Task Force lead experts. We included English-language publications evaluating the effects of screening for bilirubin encephalopathy using early total serum bilirubin (TSB), transcutaneous bilirubin (TcB) measurements, or risk scores. Severe hyperbilirubinemia was used as a surrogate for possible chronic bilirubin encephalopathy, because no studies directly evaluated the latter as an outcome. We calculated the sensitivity and specificity of early TSB, TcB measurements, or risk scores in detecting hyperbilirubinemia. RESULTS: Ten publications (11 studies) were eligible. Seven (2 prospective) studies evaluated the ability of risk factors (n = 3), early TSB (n = 3), TcB (n = 2), or combinations of risk factors and early TSB (n = 1) to predict hyperbilirubinemia (typically TSB > 95th hour-specific percentile 24 hours to 30 days postpartum). Screening had good ability to detect hyperbilirubinemia: reported area-under-the-curve values ranged between 0.69 and 0.84, and reported sensitivities and specificities suggested similar diagnostic ability. Indirect evidence from 3 descriptive uncontrolled studies suggests favorable associations between initiation of screening and decrease in hyperbilirubinemia rates, and rates of treatment or readmissions for hyperbilirubinemia compared with the baseline of no screening. No study assessed harms of screening. CONCLUSIONS: Effects of screening on the rates of bilirubin encephalopathy are unknown. Although screening can predict hyperbilirubinemia, there is no robust evidence to suggest that screening is associated with favorable clinical outcomes.
Assuntos
Dano Encefálico Crônico/prevenção & controle , Hiperbilirrubinemia Neonatal/diagnóstico , Kernicterus/prevenção & controle , Triagem Neonatal/métodos , Doença Aguda , Bilirrubina/sangue , Boston , Dano Encefálico Crônico/sangue , Dano Encefálico Crônico/epidemiologia , Feminino , Seguimentos , Humanos , Hiperbilirrubinemia Neonatal/sangue , Hiperbilirrubinemia Neonatal/epidemiologia , Incidência , Recém-Nascido , Kernicterus/sangue , Kernicterus/epidemiologia , Masculino , Valor Preditivo dos Testes , Medição de Risco , Índice de Gravidade de DoençaRESUMO
Effects of caffeic acid phenethyl ester (CAPE) on the serum S-100B levels were studied as an index for brain damage after permanent middle cerebral artery (MCA) occlusion in rabbits. Twenty rabbits were divided into four groups (n=5): control, sham, non-treatment and CAPE. The right MCA was occluded using a microsurgical procedure with bipolar coagulation and was then transected in non-treatment and CAPE groups. The rabbits in the sham group underwent a surgical procedure but the MCA was not occluded. No surgery was performed in the control group. CAPE was administered after MCA occlusion at the dose of 10 microg/kg, once a day intraperitoneally for 7 days in the CAPE group. Serum S-100B levels were determined on days 1, 2, 4 and 7. Serum S-100B level was significantly increased following permanent MCA occlusion. Posttreatment of CAPE significantly reduced the serum S-100B level. This study demonstrated that CAPE is capable of attenuating increased serum S-100B level induced by MCA occlusion in rabbits. CAPE may be useful as a neuroprotective agent.
Assuntos
Dano Encefálico Crônico/sangue , Ácidos Cafeicos/farmacologia , Infarto da Artéria Cerebral Média/sangue , Fatores de Crescimento Neural/sangue , Fármacos Neuroprotetores/farmacologia , Álcool Feniletílico/análogos & derivados , Proteínas S100/sangue , Animais , Biomarcadores/metabolismo , Dano Encefálico Crônico/tratamento farmacológico , Ácidos Cafeicos/uso terapêutico , Infarto da Artéria Cerebral Média/tratamento farmacológico , Injeções Intraperitoneais , Masculino , Fármacos Neuroprotetores/uso terapêutico , Álcool Feniletílico/farmacologia , Álcool Feniletílico/uso terapêutico , Coelhos , Subunidade beta da Proteína Ligante de Cálcio S100RESUMO
BACKGROUND: Microangiopathy-related cerebral damage (MARCD) is an entity of cerebrovascular disease based on arteriosclerosis in deep white matter, which includes lacunar infarction and white matter hyperintensity (WMH). As asymmetric dimethylarginine (ADMA), an endogenous inhibitor of the nitric oxide (NO) synthases, and homocysteine are both potential risk factors for arteriosclerosis, the plasma levels of these two substances were evaluated in individuals with MARCD. METHODS: Consecutive participants of a health examination (401 males and 311 females) were recruited for this cross-sectional study. All participants received an magnetic resonance imaging examination, and those with either lacunar infarction or WMH (grade > or =2) were classified into MARCD (+) (N = 146). The plasma ADMA concentration was measured with high performance liquid chromatography. The total homocysteine (tHcy) concentration was measured using a commercial kit. RESULTS: The ADMA level (P < 0.001), symmetric dimethylarginine (SDMA) level (P < 0.05) and L-arginine (Arg)/ADMA ratio (P < 0.01) differed significantly between MARCD (+) and (-) according to nonparametric Wilcoxon test, while the tHcy level did not (P = 0.37). Classic risk factors such as age, blood pressure, and the presence of hypertension differed significantly between the two groups as well. In the logistic analysis, the association of Arg/ADMA with MARCD remained significant (odds ratio and 95% confidence interval, 0.19 (0.05, 0.73), P < 0.05) even after adjusting for the effects of age and hypertension. CONCLUSIONS: ADMA and tHcy levels were studied in 712 subjects with or without MARCD. The Arg/ADMA ratio was suggested to be an independent risk factor for MARCD. A large-scale prospective study is warranted to confirm the causal relationship between Arg/ADMA and MARCD.