Noninvasive monitoring of evolving urinary metabolic patterns in neonatal encephalopathy.

BACKGROUND: Infants with moderate and severe neonatal encephalopathy (NE) frequently suffer from long-term adverse outcomes. We hypothesize that the urinary metabolome of newborns with NE reflects the evolution of injury patterns observed with magnetic resonance imaging (MRI). METHODS: Eligible patients were newborn infants with perinatal asphyxia evolving to NE and qualifying for therapeutic hypothermia (TH) included in the HYPOTOP trial. MRI was employed for characterizing brain injury. Urine samples of 55 infants were collected before, during, and after TH. Metabolic profiles of samples were recorded employing three complementary mass spectrometry-based assays, and the alteration of detected metabolic features between groups was assessed. RESULTS: The longitudinal assessment revealed significant perturbations of the urinary metabolome. After 24 h of TH, a stable disease pattern evolved characterized by the alterations of 4-8% of metabolic features related to lipid metabolism, metabolism of cofactors and vitamins, glycan biosynthesis and metabolism, amino acid metabolism, and nucleotide metabolism. Characteristic metabolomic fingerprints were observed for different MRI injury patterns. CONCLUSIONS: This study shows the potential of urinary metabolic profiles for the noninvasive monitoring of brain injury of infants with NE during TH. IMPACT: A comprehensive approach for the study of the urinary metabolome was employed involving a semi-targeted capillary electrophoresis-time-of-flight mass spectrometry (TOFMS) assay, an untargeted ultra-performance liquid chromatography (UPLC)-quadrupole TOFMS assay, and a targeted UPLC-tandem MS-based method for the quantification of amino acids. The longitudinal study of the urinary metabolome identified dynamic metabolic changes between birth and until 96 h after the initiation of TH. The identification of altered metabolic pathways in newborns with pathologic MRI outcomes might offer the possibility of developing noninvasive monitoring approaches for personalized adjustment of the treatment and for supporting early outcome prediction.

[THE SEARCH AFTER PROGNOSTIC TESTS OF DEVELOPMENT OF UROLITHIASIS OF PATIENTS WITH VERTEBRO-CEREBROSPINAL TRAUMA].

The article presents analysis of alterations of biochemical indicators in blood serum and day urine of 22 patients in acute and early periods after vertebro-cerebrospinal trauma. Out of total number of patients in 10 (main group) in post-traumatic period urolithiasis developed In 12 patients no signs of urolithiasis were detected These examinedpatients were included into comparative group. The reference group was composed with 20 healthy individuals. The concentration of urea, creatinine, uric acid, calcium and inorganic phosphate in blood serum and day urine were detected In patients of main group statistically significant increasing of levels of urea and creatinine was detected in blood serum relative to patients of comparative group. In examined patients of main group clearance of urea was reliably lower than both values of comparative group (up to 2.55 times; p < 0.05) and indicators of reference group (up to 3.75 times; p < 0.05). In patients of this group, clearance of uric acid also had reliable differences from indicators both in comparative group and reference group. Therefore, in patients in acute and early periods of vertebro- cerebrospinal trauma expressed disorders of biochemical indicators of blood serum and urine that can be referred to predictors of risk of development of urolithiasis in the following. The most informative tests were increasing of concentration of urea in blood serum more than 5.30 mmol/l (ratio of likelihood ofpositive test--4.26) and decreasing of clearance of uric acid and urea.

Urinary Biomarkers of Brain Diseases.

Biomarkers are the measurable changes associated with a physiological or pathophysiological process. Unlike blood, urine is not subject to homeostatic mechanisms. Therefore, greater fluctuations could occur in urine than in blood, better reflecting the changes in human body. The roadmap of urine biomarker era was proposed. Although urine analysis has been attempted for clinical diagnosis, and urine has been monitored during the progression of many diseases, particularly urinary system diseases, whether urine can reflect brain disease status remains uncertain. As some biomarkers of brain diseases can be detected in the body fluids such as cerebrospinal fluid and blood, there is a possibility that urine also contain biomarkers of brain diseases. This review summarizes the clues of brain diseases reflected in the urine proteome and metabolome.

A singular case of survival after acute methanol poisoning: toxicological and neuroimaging findings.

Acute methanol poisoning is a relatively uncommon and dangerous form of intoxication. It generally occurs after suicidal or accidental events and can be potentially fatal if not diagnosed and treated promptly. Here reported is the case of a 52-year-old Romanian man who survived acute methanol intoxication. Therefore, it was possible to monitor the clinical evolution, the arterial blood gas assay and toxicological research of methanol in blood and urine, as well as the brain damage by computed tomography and magnetic resonance imaging during a period of 20 days after the intake.

Effect of marijuana use on outcomes in traumatic brain injury.

Traumatic brain injury (TBI) is associated with significant morbidity and mortality. Several studies have demonstrated neuroprotective effects of cannabinoids. The objective of this study was to establish a relationship between the presence of a positive toxicology screen for tetrahydrocannabinol (THC) and mortality after TBI. A 3-year retrospective review of registry data at a Level I center of patients sustaining TBI having a toxicology screen was performed. Pediatric patients (younger than 15 years) and patients with a suspected nonsurvivable injury were excluded. The THC(+) group was compared with the THC(-) group with respect to injury mechanism, severity, disposition, and mortality. Logistic regression was used to determine independent associations with mortality. There were 446 cases meeting all inclusion criteria. The incidence of a positive THC screen was 18.4 per cent (82). Overall mortality was 9.9 per cent (44); however, mortality in the THC(+) group (2.4% [two]) was significantly decreased compared with the THC(-) group (11.5% [42]; P = 0.012). After adjusting for differences between the study cohorts on logistic regression, a THC(+) screen was independently associated with survival after TBI (odds ratio, 0.224; 95% confidence interval, 0.051 to 0.991; P = 0.049). A positive THC screen is associated with decreased mortality in adult patients sustaining TBI.

Post-acute brain injury urinary signature: a new resource for molecular diagnostics.

Heterogeneity within brain injury presents a challenge to the development of informative molecular diagnostics. Recent studies show progress, particularly in cerebrospinal fluid, with biomarker assays targeting one or a few structural proteins. Protein-based assays in peripheral fluids, however, have been more challenging to develop, in part because of restricted and intermittent barrier access. Further, a greater number of molecular variables may be required to inform on patient status given the multi-factorial nature of brain injury. Presented is an alternative approach profiling peripheral fluid for a class of small metabolic by-products rendered by ongoing brain pathobiology. Urine specimens were collected for head trauma subjects upon admission to acute brain injury rehabilitation and non-traumatized matched controls. An innovative data-independent mass spectrometry approach was employed for reproducible molecular quantification across osmolarity-normalized samples. The postacute human traumatic brain injury urinary signature encompassed 2476 discriminant variables reproducibly measured in specimens for subject classification. Multiple subprofiles were then discerned in correlation with injury severity per the Glasgow Comma Scale and behavioral and neurocognitive function per the Patient Competency Rating Scale and Frontal Systems Behavioral Scale. Identified peptide constituents were enriched for outgrowth and guidance, extracellular matrix, and post-synaptic density proteins, which were reflective of ongoing post-acute neuroplastic processes demonstrating pathobiological relevance. Taken together, these findings support further development of diagnostics based on brain injury urinary signatures using either combinatorial quantitative models or pattern-recognition methods. Particularly, these findings espouse assay development to address unmet diagnostic and theragnostic needs in brain injury rehabilitative medicine.

Neutrophil gelatinase-associated lipocalin as an early marker of acute kidney injury in patients with traumatic brain injury.

BACKGROUND: Recent studies have shown that urinary neutrophil gelatinase-associated lipocalin (NGAL) is rapidly up-regulated early after murine renal injury, and in patients after cardiac surgery or patients critically ill with multiple trauma. In this study, we evaluated urinary NGAL levels as a potential biomarker of early acute kidney injury (AKI) in patients with severe traumatic brain injury (TBI). METHODS: All patients with severe TBI admitted to our neurosurgical intensive care unit from March to September 2011 were enrolled prospectively. Urinary NGAL was measured using a chemiluminescent microparticle immunoassay upon admission and at 24 and 48 hours after TBI. The presence of AKI was defined by the Acute Kidney Injury Network (AKIN) criteria. RESULTS: Using AKIN criteria, a total of 13 patients were identified with AKI, an incidence of 24%. Those who subsequently developed AKI had a striking rise in urinary NGAL early after TBI and a sustained increase over the entire duration of the study. The urinary NGAL level of the AKI group was significantly higher than the group without AKI at all time points. Using a cutoff value of 53.9 ng/mL, the area under the receiver-operating characteristic curve for urinary NGAL at 48 hours was 0.876 with a sensitivity of 0.69 and specificity of 0.95. CONCLUSIONS: Increased urinary NGAL is associated with an increased occurrence of AKI in patients with severe TBI. It is possible that urinary NGAL could provide a screening tool for AKI immediately after severe TBI, and this may in turn allow early intervention to ameliorate the adverse effects of AKI.

Urine erythropoietin level is associated with kidney and brain injury in critically ill neonates.

BACKGROUND: Erythropoietin (EPO) is a glycoprotein hormone produced predominantly in the kidneys. The protective effect of exogenous EPO in hypoxic-ischemic brain injury has been thoroughly examined in neonates. However, the metabolism of endogenous EPO in neonates remains unclear. OBJECTIVES: We aimed to evaluate the concentration of urinary EPO (uEPO) in critically ill neonates and to identify possible clinical and laboratory variables that may be associated with uEPO levels. METHODS: The concentrations of EPO, cystatin-C, microalbumin, and α1-microglobulin in the first available urine sample during the initial 72 h of life were measured in 103 critically ill neonates. Clinical and laboratory data were collected for each neonate. RESULTS: There was a positive correlation between uEPO levels and urinary levels of cystatin-C (r = 0.265, p = 0.008), microalbumin (r = 0.422, p < 0.001), and α1-microglobulin (r = 0.421, p < 0.001). The concentration of uEPO was elevated in neonates who developed acute kidney injury (AKI) during the first week of life compared with those without AKI (p = 0.002) and was also elevated in neonates with brain injury, as demonstrated by ultrasound or magnetic resonance imaging, compared to neonates without brain injury (p = 0.008). An increased log10 uEPO level was associated with the occurrence of AKI (OR 2.70, p = 0.007) and brain injury (OR 2.33, p = 0.016). CONCLUSIONS: An increased urinary EPO level in the early postnatal period is significantly associated with kidney and brain injury in critically ill neonates.

Role of S100B protein in urine and serum as an early predictor of mortality after severe traumatic brain injury in adults.

S100B is a calcium-binding protein released into the blood from astroglial cells due to brain injury. Some authors have described a correlation between S100B serum concentration and severity of brain damage. There is not much information about the accuracy of urinary S100B for predicting outcome after severe traumatic brain injury (TBI). 55 patients with severe TBI were included in the study. Blood and urine samples were drawn to determine S100B levels on admission and on the subsequent 24, 48, 72 and 96 h. S100B concentrations (serum and urine) were significantly higher in patients who were dead a month after the accident compared to survivors. ROC-analysis showed that S100B at 24h post-severe TBI is a useful tool for predicting mortality (serum: AUC 0.958, urine: AUC 0.778). The best cut-offs for S100B were 0.461 µg/L and 0.025 µg/L (serum and urine respectively), with a sensitivity of 90% for both measurements and a specificity of 88.4% (serum) and 62.8% (urine). We can state that the determination of S100B levels both in urine and serum acts as a sensitive and an effective biomarker for the early prediction of mortality after severe TBI.

Biomarkers of brain damage in preterm infants.

OBJECTIVE: There is growing evidence on the usefulness of biomarkers in the early detection of preterm infants at risk for brain damage. However, among different tools Activin A, S100B protein and adrenomedullin assessment offer the possibility to investigate brain/multiorgan function and development. This could be especially useful in perinatal medicine that requires even more non-invasive techniques in order to fulfill the minimal handling in diagnostic and therapeutic strategy performance. MATERIALS AND METHODS: The concept of Unconventional Biological Fluid (UBF: urine and saliva) is becoming even stronger and regards the assessment in non-invasive biological fluids of biochemical markers involved in the cascade of events leading to brain damage. RESULTS: Activin A, S100B protein and adrenomedullin in UBF were increased in preterm newborns developing brain damage and/or ominous outcome. CONCLUSIONS: The present manuscript offers an update on the usefulness of Activin A, S100B protein an adrenomedullin in UBF as brain damage markers. The findings open a new cue on the use of these markers in daily neonatal intensive care unit (NICU) activities.

Multiple biomarkers and risk of clinical and subclinical vascular brain injury: the Framingham Offspring Study.

BACKGROUND: Several biomarkers have been individually associated with vascular brain injury, but no prior study has explored the simultaneous association of a biologically plausible panel of biomarkers with the incidence of stroke/transient ischemic attack and the prevalence of subclinical brain injury. METHODS AND RESULTS: In 3127 stroke-free Framingham offspring (age, 59±10 years; 54% female), we related a panel of 8 biomarkers assessing inflammation (C-reactive protein), hemostasis (D-dimer and plasminogen activator inhibitor-1), neurohormonal activity (aldosterone-to-renin ratio, B-type natriuretic peptide, and N-terminal proatrial natriuretic peptides), and endothelial function (homocysteine and urinary albumin/creatinine ratio) measured at the sixth examination (1995-1998) to risk of incident stroke/transient ischemic attack. In a subset of 1901 participants with available brain magnetic resonance imaging (1999-2005), we further related these biomarkers to total cerebral brain volume, covert brain infarcts, and large white-matter hyperintensity volume. During a median follow-up of 9.2 years, 130 participants experienced incident stroke/transient ischemic attack. In multivariable analyses adjusted for stroke risk factors, the biomarker panel was associated with incident stroke/transient ischemic attack and with total cerebral brain volume (P<0.05 for both) but not with covert brain infarcts or white-matter hyperintensity volume (P>0.05). In backward elimination analyses, higher log-B-type natriuretic peptide (hazard ratio, 1.39 per 1-SD increment; P=0.002) and log-urinary albumin/creatinine ratio (hazard ratio, 1.31 per 1-SD increment; P=0.004) were associated with increased risk of stroke/transient ischemic attack and improved risk prediction compared with the Framingham Stroke Risk Profile alone; when the <5%, 5% to 15%, or >15% 10-year risk category was used, the net reclassification index was 0.109 (P=0.037). Higher C-reactive protein (ß=-0.21 per 1-SD increment; P=0.008), D-dimer (ß=-0.18 per 1-SD increment; P=0.041), total homocysteine (ß=-0.21 per 1-SD increment; P=0.005), and urinary albumin/creatinine ratio (ß=-0.15 per 1-SD increment; P=0.042) were associated with lower total cerebral brain volume. CONCLUSION: In a middle-aged community sample, we identified multiple biomarkers that were associated with clinical and subclinical vascular brain injury and could improve risk stratification.

Augmented creatinine clearance in traumatic brain injury.

BACKGROUND: Hypertonic saline and/or norepinephrine infusion are routinely used to achieve a desired cerebral perfusion pressure (CPP) in the management of traumatic brain injury (TBI). We hypothesized that creatinine clearances (CrCls) would be significantly augmented in this setting. METHODS: This was an observational cohort study in TBI patients older than 16 years with normal serum creatinine concentrations, requiring maintenance of CPP. Eight-hour urinary CrCl collections were performed while on and off active management. Demographic data, use of vasoactive medications, fluid balance, feeding regimen, and hemodynamic variables were recorded throughout the study period. Augmented CrCl was defined as >150 mL/min/1.73 m(2) in women and >160 mL/min/1.73 m(2) in men. RESULTS: Twenty patients were enrolled, and augmented clearances were demonstrated in 17 (85%). The mean maximum CrCl was 179 mL/min/1.73 m(2) while receiving CPP therapy (95% confidence interval [CI], 159-198), returning to a mean of 111 mL/min/1.73 m(2) (95% CI, 91-131; P < 0.001) when measured after discharge from the intensive care unit. The mean CrCl in the intensive care unit while not receiving CPP therapy was 150 mL/min/1.73 m(2) (95% CI, 134-167; P = 0.03). The mean time to reach peak CrCl while receiving active treatment was 4.7 days (95% CI, 3.0-6.4). In a multivariate analysis, norepinephrine use, saline loading, mean arterial blood pressure, and central venous pressure were associated with augmented CrCl on the day of measurement. CONCLUSIONS: Augmented CrCls are common in TBI patients receiving active management of CPP and persist even after discontinuation of such therapy. Further work is needed to clarify the impact of such clearances on renally excreted drugs in this setting.

Correlation between catecholamine levels and outcome in patients with severe head trauma.

Some studies have shown that catecholamines and the changes in their levels during and after head trauma can be useful in predicting the outcome in head trauma patients. The goal of this study is to search for a probable relation between urine levels of catecholamines and prognosis in patients with severe head trauma. Fifty four patients with severe head trauma Glasgow Coma Scale (GCS < or = 8) on admission time were recruited in Imam Reza Hospital within one. These patients were included when having no major accompanying trauma in other organs. Twenty four hour urine was collected after admission and levels of metanephrine and nor-metanephrine were measured. The relation between urine levels of these metabolites with final outcome and also with GCS at admission, 24, 48 h and 1 week after admission and discharge time and Glasgow Outcome Scale (GOS) were studied. Fifty two patients, 48 males and 4 females with a mean age of 32.3 +/- 14.7 (3-72) years were included. The main underlying etiologies were motorcycle (46.2%) and car accidents (25%). Diffuse axonal injury, brain contusion and subdural hematoma were three main diagnoses (28.8, 17.3 and 15.4% of the cases, respectively). 19 (36.5%) of the patients expired within the study period. The mean level of metanephrine and normetanephrine in urine were 207.9 +/- 200.5 and 330.2 +/- 218.4 microg in 24 h, respectively. There was no meaningful relation between urine levels of these metabolites and any of GCS and GOS. There was also no meaningful relation between these parameters and final prognosis in patients.

Can admission S-100beta predict the extent of brain damage in head trauma patients?

BACKGROUND: As has been shown previously, S-100beta levels in serum can be a useful predictor of brain damage after head trauma. This pilot study was designed to investigate whether urine samples, which are much easier to obtain, could be used for the same purpose instead of serum samples. METHODS: Ninety-six consecutive patients admitted with head trauma were recruited in the study. After exclusion of 54 patients, mostly because of significant additional trauma, S-100beta levels were analyzed in serum and urine of 42 patients using a luminometric assay. A range for normal values was established based on samples from ten healthy volunteers. RESULTS: S-100beta serum levels increased proportional to the severity of the head trauma, as had been previously shown by several other groups. In many patients, initial increases in urine S-100beta levels were seen later than in serum, after which the kinetics of S-100beta levels in urine seemed to follow that established for serum levels. S-100beta values in urine were on average about 54% lower in urine than in serum. CONCLUSIONS: S-100beta levels in urine obtained on admission to the hospital are not a good indicator for the extent of brain damage. However, urine S-100beta levels obtained at later time points might be a useful indicator for the development of secondary brain injury.

Brain injury in glutaric aciduria type I: the value of functional techniques in magnetic resonance imaging.

BACKGROUND: Acute striatal necrosis is a devastating consequence of encephalopathic crisis in patients with glutaric aciduria type I (GA-I), but the mechanisms underlying brain injury are not completely understood. OBJECTIVE: To approach pathophysiological aspects of brain injury in GA-I by means of functional techniques in magnetic resonance imaging (MRI). PATIENTS AND METHODS: Four patients during an acute encephalopathic crisis and three asymptomatic siblings with GA-I underwent single-voxel hydrogen magnetic resonance spectroscopy (MRS) and brain MRI including gradient echo T1-weighted, FLAIR, T2-weighted and diffusion-weighted imaging. RESULTS: The study was performed between three and eight days after the onset of acute encephalopathic crisis. Isotropic diffusion images showed high signal changes with corresponding low apparent diffusion coefficient values within the putamen, caudate nuclei and globus pallidus (four patients), and the cerebral peduncles including the substantia nigra (one patient). The study disclosed normal findings in asymptomatic siblings. MRS showed decreased N-acetyl-aspartate/creatine ratio at the basal ganglia in encephalopathic patients when compared to a group of sex- and age-matched controls. CONCLUSIONS: Brain injury in GA-I is characterized by the presence of cytotoxic edema and reduced neuronal integrity by functional imaging techniques. Involvement of the basal ganglia may be asymmetrical in patients with unilateral motor disorder and may extent to the cerebral peduncles and substantia nigra, which may be responsible for the acute onset dystonia in some patients. Functional techniques failed to demonstrate any abnormalities in asymptomatic patients, which is in agreement with the integrity of basal ganglia structures observed by conventional MRI sequences.

Indicators of lean body mass catabolism: emphasis on the creatinine excretion rate.

BACKGROUND: The major stress response to critical illness leads to a catabolic state and loss of lean body mass. AIMS: To test whether an increased rate of creatinine excretion might provide unique and timely information to monitor cell catabolism; to relate this information to balances of cell constituents (nitrogen, potassium, phosphate and magnesium); to evaluate the effectiveness of nutritional therapy to reverse this catabolic process. DESIGN: Prospective observational study. METHODS: Children with severe traumatic brain injury admitted to the paediatric critical care units of The Hospital for Sick Children, Toronto, Canada and Hospital das Clínicas, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil were studied. Complete 24 h urine collections were obtained for measurement of creatinine excretion rate and daily balances of nitrogen, potassium, phosphate and magnesium. RESULTS: Seventeen patients were studied for 3-10 days. On Day 1, all had negative balances for protein and phosphate. Balances for these intracellular constituents became positive when protein intake was >/=1 g/kg/day and energy intake was >/=50% of estimated energy expenditure (P < 0.0001). Creatinine excretion rate was positively correlated with the urea appearance rate (r = 0.60; P < 0.0001), and negatively with protein balance (r = -0.45; P < 0.0001). Sepsis developed in four patients; before its clinical detection, there were negative balances for all intracellular markers and an abrupt rise in the excretion of creatinine. CONCLUSION: Negative balances of intracellular components and an increase in rate of creatinine excretion heralded the onset of catabolism.

Vasopressin serum levels and disorders of sodium and water balance in patients with severe brain injury

BACKGROUND: Disorders of water and sodium balance are frequently seen in patients with severe brain injury (SBI), and may worsen their prognosis. PURPOSE: To evaluate vasopressin (AVP) serum levels and sodium and water balance disorders during the first week post-injury in patients with SBI. METHOD: Thirty-six adult patients with SBI (admission Glasgow Coma Scale score < 8) and an estimated time of injury < 72 hours were prospectively studied. Clinical and laboratory data were recorded and AVP was measured in venous blood samples collected on the 1st, 2nd, 3rd and 5th days following inclusion. RESULTS: AVP serum levels remained within the normal range in SBI patients (either traumatic or non-traumatic), although tended to be greater in non-survivor than in survivor patients (p=0.025 at 3rd day). In-hospital mortality was 43 percent (15/36), and serum sodium and plasma osmolality variabilities were greater in non-survivor than in survivor patients during the observation period (p<0.001). CONCLUSION: AVP serum levels remained within the normal range values in these SBI patients, but those who died have shown higher incidence of abnormal sodium and water balance during the first week post-injury.

ANTECEDENTES: Desordens do balanço de água e sódio são frequentemente vistas em pacientes com lesão cerebral grave (LCG), podendo agravar o prognóstico. OBJETIVO: Avaliar os níveis séricos de vasopressina (AVP) e a incidência de distúrbios da água e sódio na primeira semana pós-lesão em pacientes com LCG. MÉTODO: Trinta e seis pacientes adultos com LCG (pontuação inicial na escala de coma de Glasgow < 8) e tempo estimado de lesão < 72h foram estudados prospectivamente. Dados laboratoriais e clínicos foram registrados e os níveis séricos de AVP foram mensurados no 1º, 2º, 3º e 5º dias pós-inclusão. RESULTADOS: A AVP manteve-se dentro da faixa de normalidade nestes pacientes, mas mostrando-se proporcionalmente mais elevada nos pacientes que não sobreviveram (p=0,025 no 3º dia). A mortalidade intra-hospitalar foi 43 por cento (15/36) e as variações do sódio e osmolalidade plasmáticos foram maiores nos pacientes que não sobreviveram durante o período de observação (p<0,001). CONCLUSÃO: Os níveis séricos de AVP mantiveram-se dentro da faixa de normalidade nestes pacientes com LCG, mas aqueles não sobreviventes mostraram maior incidência de anormalidades do balanço de água e sódio durante a primeira semana de evolução.

Vasopressin serum levels and disorders of sodium and water balance in patients with severe brain injury.

BACKGROUND: Disorders of water and sodium balance are frequently seen in patients with severe brain injury (SBI), and may worsen their prognosis. PURPOSE: To evaluate vasopressin (AVP) serum levels and sodium and water balance disorders during the first week post-injury in patients with SBI. METHOD: Thirty-six adult patients with SBI (admission Glasgow Coma Scale score < or= 8) and an estimated time of injury