BNP and NT-proBNP Concentrations in Paired cerebrospinal Fluid and Plasma Samples of Patients with Traumatic Brain Injury.

BACKGROUND: The aim of this study was to investigate the secretion patterns of brain natriuretic peptide (BNP) and N-terminal-proBNP (NT-proBNP) after traumatic brain injury (TBI) and to analyze the source of them in cerebrospinal fluid (CSF). MATERIALS AND METHODS: We synchronously measured BNP and NT-proBNP concentrations in paired CSF and plasma samples from 22 moderate to severe TBI patients and 40 healthy control patients. The CSF and/or plasma ratio of albumin (QAlbumin) was calculated daily. The BNP and NT-proBNP levels of CSF and plasma were compared between TBI patients and control patients. RESULTS: CSF BNP and NT-proBNP levels peaked on day 3 after injury, as did the plasma BNP and NT-proBNP levels. The CSF BNP and NT-proBNP levels in TBI patients were elevated from day 1, which was significantly higher than control group (P < 0.05 and P < 0.01, respectively). However, in plasma, only NT-proBNP levels were significantly higher than in the control group from day 2 (P < 0.05). In addition, QBNP, defined as CSF BNP concentration and/or plasma BNP concentration, was significantly higher in TBI patients than in the control group (P < 0.01). However, QAlbumin remained within ranges of a mild to moderate dysfunction of blood-brain-barrier in TBI patients. CONCLUSIONS: CSF BNP concentrations are elevated and peak on day 3 after moderate to severe TBI. CSF BNP may originate from the brain and may be a potential biomarker of TBI.

Hyperthermia and postmortem biochemical investigations.

The postmortem diagnosis of heat-related deaths presents certain difficulties. Firstly, preterminal or terminal body temperatures are often not available. Additionally, macroscopic and microscopic findings are nonspecific or inconclusive and depend on survival duration after exposure. The diagnosis of hyperthermia is therefore essentially based on scene investigation, the circumstances of death, and the reasonable exclusion of other causes of death. Immunohistochemistry and postmortem biochemical investigations have been performed by several authors in order to better circumstantiate the physiopathology of hyperthermia and provide further information to confirm or exclude a heat-related cause of death. Biochemical markers, such as electrolytes, hormones, blood proteins, enzymes, and neurotransmitters, have been analyzed in blood and other biological fluids to improve the diagnostic potential of autopsy, histology, and immunohistochemistry. The aim of this article is to present a review of the medicolegal literature pertaining to the postmortem biochemical investigations that are associated with heat-related deaths.

Natriuretic pro-peptides in idiopathic intracranial hypertension.

Idiopathic intracranial hypertension is a disorder of unknown pathogenesis. Natriuretic peptides may be involved in intracranial pressure regulation, but cerebrospinal fluid (CNS) and plasma concentrations in this disorder are unknown. We evaluated venous and intrathecal concentrations of ANP, BNP and CNP precursor peptides in 40 patients with idiopathic intracranial hypertension and in 20 controls. Natriuretic pro-peptides were quantitated using processing-independent assays. In CSF, no differences in peptide concentrations between patients and controls were found (proANP: 239 + or - 23 vs 231 + or - 22 pmol/L, proBNP: <2 pmol/L in all, proCNP: 1079 + or - 318 vs 1138 + or - 323 pmol/L). In plasma, proCNP was lower in IIH compared with controls (35.3 + or - 4.8 pmol/L vs 43.8 + or - 5.9 pmol/L, p<0.0001). Moreover, plasma proBNP was significantly lower in patients compared with controls (47.1 + or -21.4 pmol/L vs 59.2 + or - 22.0 pmol/L, p = 0.045). There were no associations between peptide concentrations and ICP and BMI, respectively. Plasma proANP and proCNP increased during 3 months follow-up (p=0.01 and p=0.006), n=12. We suggest that decreased plasma proCNP concentration in idiopathic intracranial hypertension may reflect endothelial dysregulation of vascular tone and may be a marker in this disease. Further studies of proCNP and endothelial function are needed to establish such role.

Cerebrospinal fluid and serum NT-proBNP concentrations in children with epilepsy.

INTRODUCTION: The cardio-neuro-endocrine axis seems to be involved in the cascade of postictal events in children. The aim of this study was to assess the relationship between childhood epilepsy and cerebrospinal fluid (CSF) or serum concentrations of the N-terminal pro B-type natriuretic peptide (NT-proBNP) interictally. METHODS: A total of seventy-four children agreed to participate in the study. Twenty-two children with epilepsy and mild developmental delay (mean+/-SD [median] age 5.8+/-4.9 [4.3] years), 15 children with newly diagnosed multiple sclerosis (MS) (15.1+/-1.4 [15.3] years) and 37 children with cryptogenic mild developmental delay (8.0+/-4.6 [7.4] years), serving as controls, were eligible. RESULTS: In children with epilepsy, interictal CSF NT-proBNP concentrations were greater when compared to the MS group and to controls (mean+/-SD [median] 193.0+/-78.1 [176.0]ng/L vs. 147.8+/-60.2 [138.0]ng/L vs. 140.4+/-36.5 [134.0]ng/L; p=0.014 and p=0.009). In contrast, serum NT-proBNP concentrations and the CSF/serum NT-proBNP ratio did not differ between groups. DISCUSSION: Greater CSF NT-proBNP concentrations in children with epilepsy may reflect an unspecific activation of the cardio-neuro-endocrine system involving endocrinological stress-response mechanisms interictally. The relationship between epilepsy and the cardio-neuro-endocrine axis may further the understanding of seizure susceptibility in children as well as influences of epilepsy on central modulation of autonomic cardiovascular control.

Intrathecal and systemic concentration of NT-proBNP in patients with severe traumatic brain injury.

Outcome of patients suffering from traumatic brain injury (TBI) depends on the development of secondary brain damage. In this context, recent studies underlined the role of the natriuretic peptides- atrial natriuretic peptide and brain natriuretic peptide (BNP)-in aneurysmatic subarachnoidal hemorrhage (SAH). Especially BNP correlates with intracranial pressure and clinical outcome after SAH. Since its role in TBI remains unclear, the intracranial and systemic concentrations of N-terminal (NT)-proBNP were analyzed in patients suffering from severe TBI. We measured NT-proBNP levels in cerebrospinal fluid (CSF) and serum of 14 patients suffering from severe TBI (GCS15 mm Hg (n=6), the serum (800+/-150 pg/mL) and CSF levels (55+/-9 pg/mL) of NT-proBNP were significantly increased after 24 h, as compared to patients with ICP15 mm Hg. Further studies are currently performed to elucidate the physiologic role of NT-proBNP in TBI.

The neuro-cardio-endocrine response to acute subarachnoid haemorrhage.

OBJECTIVE: Whereas cardiac hormones increase after subarachnoid haemorrhage (SAH), and may contribute to sodium wastage and hyponatraemia, there is controversy concerning the relative roles of atrial natriuretic peptide (ANP) vs. brain natriuretic peptide (BNP) and the factors initiating their secretion. Noting previous work linking stress hormone responses with cardiac injury after SAH, we have studied responses in stress hormones, markers of cardiac injury and the temporal changes in ANP and BNP and related them to changes in sodium status post ictus and during recovery from acute SAH. DESIGN, PATIENTS, MEASUREMENTS: Eighteen patients with verified SAH of variable severity were studied in a single unit for a 14-day period post ictus under controlled conditions of sodium and fluid intake. All received a standardized protocol of daily dexamethasone and nimodipine throughout the study. Severity was graded using criteria of Hess and Hunt at admission. Stress hormones (AVP, catecholamines and admission plasma cortisol), markers of cardiac injury (ECG and daily plasma troponin T) and cardiac hormones (ANP and BNP) were measured daily and related to severity, plasma sodium and renin-aldosterone activity. Hormone levels (ANP, BNP and endothelin) in cerebrospinal fluid (CSF) were also measured in nine patients. RESULTS: Intense neurohormonal activation (AVP, cortisol and catecholamines) at admission was associated with increased levels of both plasma ANP and BNP whereas levels in CSF were unaffected. In individual patients plasma levels of ANP and BNP were strongly correlated (P < 0.001). Cardiac events (abnormal ECG and/or elevated troponin) occurred in six of seven patients graded severe but neither stress hormones nor cardiac peptides differed significantly in patients with mild (n = 11) vs. severe (n = 7) SAH. During the course of a progressive fall in plasma sodium concentration (P = 0.001), there was a delayed activation of renin-aldosterone which was inversely correlated with declining levels of plasma ANP/BNP (P < 0.002). CONCLUSIONS: Excessive secretion of both ANP and BNP occurs in all patients after acute subarachnoid haemorrhage and is unrelated to severity, stress hormone activation or markers of cardiac injury. Inhibition of renin-aldosterone by cardiac hormones may impair renal sodium conservation and contribute to developing hyponatraemia. In the absence of evidence for activation of natriuretic peptides within the brain, the prompt and consistent increase in both ANP and BNP strongly supports the view that the heart is the source of increased natriuretic peptide secretion after acute subarachnoid haemorrhage.