Biochemical analysis of the cerebrospinal fluid: evidence for catastrophic energy failure and oxidative damage preceding brain death in severe head injury: a case report.

OBJECTIVES: To compare biochemical and clinical parameters in a case of fatal severe traumatic brain injury (TBI) with secondary insult. DESIGN AND METHODS: A TBI patient was catheterized for intracranial pressure (ICP) monitoring and cerebrospinal fluid (CSF) analysis of ascorbate, malondialdehyde, oxypurines, and nucleosides. RESULTS: Oxidative brain damage preceded ATP catabolite increment in the CSF even with ICP below 20 mm Hg. Sustained oxidative stress caused irreversible energy state derangement followed by a refractory ICP rise. Massive oxypurine and nucleoside release was recorded 36 h before brain death. CONCLUSIONS: Molecular events, detected by biochemical CSF analysis and preceding modification of clinical parameters in severe TBI with secondary insult, are discussed.

[Monoamines, monoamine metabolites, neuron specific enolase and myelin basic protein concentrations in cerebrospinal fluid of resuscitated patients].

Changes of monoamines, monoamine metabolites, neuron specific enolase (NSE) and myelin basic protein (MBP) levels in cerebrospinal fluid were measured in 8 patients for up to 7 days after cardiopulmonary resuscitation. The outcomes were assessed by the Glasgow Outcome Scale. One showed good recovery 3 developed a persistent vegetate state (PVS) and 4 became brain dead (BD). The concentration of NSE increased to a peak about 3 days after resuscitation, then gradually decreased. MBP also showed an increase with time up to 7 days. The time course suggests that neuronal and/or axonal damage progresses for several days after hypoxic or anoxic brain insult. NSE and MBP in the BD group were higher than those in the PVS group, thus CSF levels may be prognostic with regard to hypoxic brain injury. Tyrosine, dopamine, 3-methoxytyramine (3-MT), 3-dihydroxy-4-phenylacetic acid (DOPAC), homovanillic acid (HVA), vanillylmanderic acid (VMA), normetanephrine (NMN), metanephrine (MN), 3-methoxy-4-hydroxyphenylglycol (MHPG), vanillic acid (VA), tryptophan and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were analyzed by HPLC with an electrochemical detector. Concentrations changed within 2 or 3 days after resuscitation, so concentrations at that period may indicate neuronal damage. However, there are some cases with abnormal NSE and MBP levels without abnormal monoamine levels, suggesting that differences in concentrations are not the consequence of the amount of affected neurons, but of the sites of regions.

[An increase in cerebrospinal fluid ubiquitin in human global brain ischemia--a prognostic marker for anoxic-ischemic encephalopathy].

The prognostic value of ubiquitin levels in cerebrospinal fluid (CSF) was studied in human global brain ischemia (anoxic-ischemic encephalopathy). Twenty four samples were collected from 13 patients who were resuscitated from cardio-pulmonary arrest and survived for at least 1 day. The outcome was classified according to the Glasgow Outcome Scale (GOS1-5). The ubiquitin levels (normal: 14.3 +/- 1.1 ng/ml, mean +/- S.E.M.) in neurologically symptomatic patients (GOS1-4) were 151 +/- 32.5 ng/ml on day 1-2 and elevated to 1,960 +/- 849 ng/ml on day 3-4. The Spearman's rank correlation of ubiquitin levels on day 3-4 and the GOS was -0.855, showing a better correlation than CSF neuron-specific enolase levels (r = -0.846). Ubiquitin is a heat shock protein associated with the degradation of abnormal cellular proteins. Thus, the elevation of CSF ubiquitin levels represents both its overproduction by a cytoprotective response to brain ischemia and its leakage from the damaged tissue. The present study suggests that the measurement of CSF ubiquitin level is useful for the early prognostic assessment of global brain ischemia.

Maternal brain death during pregnancy.

A case of a 36-year-old woman diagnosed brain dead secondary to pneumococcal meningitis at 27 weeks of gestation is presented. In spite of aggressive therapy, supportive intensive care was possible for only 36 h. Signs of fetal distress appeared and a cesarean section was performed. The complexity of supportive care and its ethical implications are discussed.

Critical evaluation of postmortem changes in human autopsy cisternal fluid. Enzymes, electrolytes, acid-base balance, glucose and glycolysis, free amino acids and ammonia. Correlation to total brain ischemia.

By studying early postmortem changes in cerebrospinal fluid (CSF) it is possible to draw conclusions as to premortem focal brain cell injury and terminal brain ischemia. Cisternal fluid (CF) from 40 different adult cadavers with no known neurological disorder was analyzed and compared with known in vivo values. They were divided into four groups (n = 10 in each group), CF samples taken 2, 4, 10, and 24 h after death. The enzyme activity of CK and CK-BB (EC 2.7.3.2) increased linearly and statistically significantly 4-24 h postmortem (P < 0.001) the 2 h values being already 10 to 20 times higher than in vivo, LD and its isoenzymes 1 to 3 (EC 1.1.1.27) distinctly 10 to 24 h after death. Glucose and pyruvate concentrations in the CF declined, as did Na+ and Cl-. Lactate and K+ increased over time. The earliest statistically significant changes between different timepoints were seen in lactate, pyruvate and K+ concentrations. The GABA concentration was already more than 170 times at 2 h postmortem, and glutamate more than 20 times higher than in vivo. The concentrations of alanine, glycine, lysine, histidine, isoleucine, phenylalanine, and tyrosine were 2 to 3 times higher at 2 h postmortem than during life. The concentrations of all amino acids and ammonia increased linearly and statistically significantly (P < 0.001) in the CF 4 to 24 h postmortem.

Diagnóstico precoce da morte cerebral através do exame do líquido cefalorraquidiano: estudo em pacientes críticos com especial referência ao comportamento dos íons potássio e magnésio após a morte

O comportamento dos níveis liquóricos dos íons potássio e magnésio foi estudado prospectivamente em quatro pacientes comatosos com extensas lesöes do SNC e em quatro pacientes com morte cerebral diagnosticada nas últimas 24 horas e confirmada por EEC isoelétrico. Nos pacientes comatosos, os resultados foram K(mEq/l) - 2,4; 2,7; 2,7; 2,8 (média 2,65); Mg (mg/dl) - 2,6; 2,6; 2,4; 2,48 (média 2,52). Estes achados reafirmam a grande estabilidade das concentraçöes liquóricas de k e Mg no homem, mesmo após grave dano ao SNC. Houve uma grande variabilidade dos níveis de cátions encontrados logo após a morte cerebral. Em apenas um caso o diagnóstico näo foi seguido de aumento significativo do teor de K no LCR (2, 2; 3,1; 3, 4; 6,5 - 3,8 mEq/1). Os níveis de Mg näo demonstraram tendência clara a elevaçäo, mas os valores encontrados tenderam a dispersäo ampla (2,8; 2,8; 18; 1,6 - média 2,25 mg/dl). A integridade cerebral parece depender do controle estrito dos níveis de K e Mg no LCR. O achado de valores fora destes limites em um pacientes comatoso preenchendo critérios clínicos de morte cerebral poderia permitir seu diagnóstico precoce. Esta sugestäo exige, porém, maior número de doentes, incluindo condiçöes complicadoras, como choque, intoxicaçöes exógenas e hipotermia. O risco da punçäo espinhal neste contexto também exige investigaçäo. O achado ocasional de níveis normais de K e de valores muito variáveis de Mg sugere a persistência de mecanismos de captaçäo celular ativa dos íons, possivelmente de origem medular