Screening for Fatal Traumatic Brain Injuries in Cerebrospinal Fluid Using Blood-Validated CK and CK-MB Immunoassays.

A single, specific, sensitive biochemical biomarker that can reliably diagnose a traumatic brain injury (TBI) has not yet been found, but combining different biomarkers would be the most promising approach in clinical and postmortem settings. In addition, identifying new biomarkers and developing laboratory tests can be time-consuming and economically challenging. As such, it would be efficient to use established clinical diagnostic assays for postmortem biochemistry. In this study, postmortem cerebrospinal fluid samples from 45 lethal TBI cases and 47 controls were analyzed using commercially available blood-validated assays for creatine kinase (CK) activity and its heart-type isoenzyme (CK-MB). TBI cases with a survival time of up to two hours showed an increase in both CK and CK-MB with moderate (CK-MB: AUC = 0.788, p < 0.001) to high (CK: AUC = 0.811, p < 0.001) diagnostic accuracy. This reflected the excessive increase of the brain-type CK isoenzyme (CK-BB) following a TBI. The results provide evidence that CK immunoassays can be used as an adjunct quantitative test aid in diagnosing acute TBI-related fatalities.

Cardiac biomarkers in blood, and pericardial and cerebrospinal fluids of forensic autopsy cases: A reassessment with special regard to postmortem interval.

Previous studies suggested possible application of postmortem biochemistry of myocardial biomarkers to the investigation of sudden cardiac death; however, differences from clinical findings should be considered in autopsy materials. The present study involved a comprehensive investigation of cardiac troponin T and I (cTnT and cTnI), and creatine kinase MB (CK-MB) in cardiac and peripheral external iliac venous blood, pericardial fluid (PCF) and cerebrospinal fluid (CSF) for reassessment, with special regard to the estimated postmortem interval in relation to the cause of death, reviewing a large number of forensic autopsy cases (n=1923). These cardiac biomarkers showed cause-of-death- and postmortem-time-dependent differences: blood and PCF levels of each marker were higher in hyperthermia (heatstroke), bathwater drowning and chronic congestive heart disease in cases of postmortem interval (PMI) <12h. After 12h postmortem, these markers were also higher in fatal drug abuse, spontaneous cerebral/subarachnoid bleeding, electrocution and pulmonary embolism. In addition, most other causes of death, including ischemic heart disease, showed substantial elevations, while these markers remained low in acute hemorrhagic death from sharp instrument injury, hypothermia (cold exposure) and sea-/freshwater drowning during PMI of <48h. CSF cTnI and CK-MB showed similar findings. There was no difference between myocardial infarction and other causes of death to be discriminated, including asphyxiation, drowning and fire fatality. These findings are similar to clinical observations in critical ill patients, suggesting that elevated cardiac biomarkers cannot be a specific finding for death from acute ischemic heart disease, but indicate the severity of myocardial injury in postmortem investigation.

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.

Combined analyses of creatine kinase MB, cardiac troponin I and myoglobin in pericardial and cerebrospinal fluids to investigate myocardial and skeletal muscle injury in medicolegal autopsy cases.

Creatine kinase-MB (CK-MB), cardiac troponin I (cTnI) and myoglobin (Mb) are biochemical markers of myocardial injury; however, Mb is more abundant in skeletal muscles. The present study involved analysis of these markers in pericardial and cerebrospinal fluids (PCF and CSF) from serial medicolegal autopsy cases (n=295, within 48h) to examine their efficacy in determining the cause of death. Although these markers showed a slight postmortem time-dependent elevation, except for CK-MB in CSF, the distribution depended on the cause of death. Mb levels in PCF and CSF were higher in fatal hyperthermia (heat stroke) and methamphetamine abuse, and CK-MB in both fluids was also higher in the latter. In psychotropic drug intoxication, CK-MB, cTnI and Mb were higher in PCF, but only cTnI was elevated in CSF. In electrocution and cerebrovascular disease, each marker was higher in PCF and also relatively high in CSF. PCF cTnI level was higher in acute pulmonary embolism without significant elevation of any other markers, whereas CSF CK-MB was higher in acute blunt brain injury death and methamphetamine abuse. In most cases of delayed brain injury death, hypothermia (cold exposure) and pneumonia, these markers were low or intermediate in both PCF and CSF; however, sudden cardiac death, asphyxiation and fire fatality cases showed few characteristic findings. These observations suggest that combined analyses of these markers in postmortem PCF and CSF, in addition to blood samples, are helpful for evaluating the severity of myocardial and/or skeletal muscle damage in death processes, in particular for investigating deaths due to hyperthermia, hypothermia, electrocution and intoxication.

Analysis of cardiac troponins and creatine kinase MB in cerebrospinal fluid in medicolegal autopsy cases.

Previous studies suggested the usefulness of postmortem cardiac troponin (cTn) and creatine kinase MB (CKMB) levels in blood and pericardial fluid for investigating myocardial damage in the death process. The present study investigated the postmortem levels in cerebrospinal fluid (CSF), using serial medicolegal autopsy cases (n=257, within 48h postmortem). For CSF, the postmortem increase was slight for cTnT and cTnI, and was not significant for CKMB. A moderate correlation was seen between cTnT and cTnI levels (r=0.598, p<0.0001), whereas the correlations of cTnT and cTnI with CKMB were insignificant. The correlation between peripheral blood and CSF levels was significant for cTnT and cTnI, but insignificant for CKMB. Marked concomitant increases in CSF cTnT and cTnI levels were seen for protracted asphyxiation and hyperthermia (heat stroke). In addition, marked elevation of CSF cTnI was detected in some cases of acute cardiac death. Increased CKMB was apparently independent of the cause of death, and was frequently seen in acute or subacute deaths. These findings suggest that CSF levels of cTnT and cTnI are useful for investigating the progress and duration of myocardial damage in the death process. CKMB may be used as a marker of persistent hypoxic myocardial damage before death.