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Results: The biomarkers S 100 neuron specific enolase, neurofilament light chain, and Glial fibrillary acidic protein are significantly increased in cases of (experimental) spinal cord injury. Furthermore, increased serum concentrations of S 100 have been correlated with an unfavourable functional outcome. Although biomarkers in SCI show promising results, considerations and shortcomings, such as polytrauma, haemolysis, extracerebral sources, and poor resuscitation, must be studied in greater detail before biomarkers can be utilised in the clinical care of SCI.
Conclusions: Quantitative standards for determining the extent of SCI during the acute phase must be developed and Elite Mens Byron Maxwell jersey validated. Youth Brad Smith Byron Maxwell jersey jersey Even though increased concentrations of neurochemical biomarkers have been identified in patients Elite Black Darren Sproles jersey with SCI, these do not yet provide a sensitive prognostic tool. Considering the limited availability of sensitive prognostic tools, neurochemical biomarkers of SCI should be evaluated and validated in future clinical trials.
Keywords: biomarkers, spinal cord injury, cerebrospinal fluid, serum, trauma
Top of pageIntroductionIn traumatic spinal cord injury (SCI), much effort has been put into the evaluation of SCI severity and prediction of recovery potential. Interventions for the recovery of function following SCI include a combination of pharmacological,1 surgical2 and rehabilitation3 approaches. The benefits of these interventions, however, are not univocal in clinical trials. It is assumed that patients Elite Youth Brandon Graham jersey with more severe SCI respond differently to neuroprotective interventions than do patients with less severe SCI.3 An accurate prediction of the initial damage of the spinal cord that differentiates between the different severities of SCI may help physicians in Authenitc Youth Darren Sproles jersey choosing an available or experimental neuroprotective intervention in the very acute phase.
Conventional magnetic resonance imaging (MRI) is currently the best imaging modality for evaluating traumatic SCI during the very acute phase.4 Although several MRI findings such Youth Donnie Jones jersey as parenchymal hemorrhage, transection and longer lesion length correlate with less favorable neurological outcomes, the findings on neurological examinations are most predictive of outcomes.5 Prediction of functional outcome by means of the American Spinal Injury Association (ASIA) motor scores is considered to be reliable and prognostic in patients with motor complete SCI when tested 72 after the initial trauma.6, 7 Combining Elite Brad Smith jersey the results of MRI and initial neurological examination results in an even better prediction of the recovery of motor scores.8, 9 However, early ASIA examinations (for Kids Byron Maxwell Womens Brad Smith jersey jersey example, within 72 post injury) are considered unreliable.6
Therefore, an early, accurate diagnostic test with the purpose of indicating neuroprotective interventions is preferable. Conventional MRI appears to be restricted to assessing macroscopic changes in the injured spinal cord, as it does not adequately address axonal injury in the white matter. As the degree and localization Elite Black Byron Maxwell jersey of injured and spared white matter primarily determine functioning Authenitc Darren Sproles jersey after SCI, MRI has limited success as a prognostic tool.5 MRI is largely a qualitative measure Authenitc Black Brandon Graham jersey and quantitative standards, in relation to functional SCI outcomes, will need to be developed and validated.3
A new approach for evaluating the primary cord damage in the acute phase may be the assessment of biomarker concentrations in the cerebrospinal fluid (CSF). Trauma to the spinal cord causes an acute physical injury with neuronal necrosis. This is followed by a secondary axonal degeneration and further degeneration or death of nerve cells by either apoptosis or necrosis, processes that may last between days and weeks. As the spinal cord is surrounded by the CSF, damage to the spinal cord may lead to the release of proteins and metabolites from the nervous tissue into the CSF. This process allows for the study of of SCI in the CSF.10, 11, 12 A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal or pathologic processes or pharmacologic responses to a therapeutic intervention.13
Biomarkers of SCI can be approached in two ways: (1) a direct survey of primary Authenitc Blue Byron Maxwell jersey structural damage using a specific unique marker (or markers) of tissue damage, and (2) measure aspects of the cellular, Elite Blue Brandon Graham Authenitc Blue Brad Smith jersey jersey biochemical or molecular cascades in the secondary injury (or repair) response phase.14 An ideal prognostic central nervous system (CNS) biochemical marker should have all of the following properties:15There has been growing interest in biomarkers as indicators of tissue destruction in CNS diseases. Several studies have indicated that monitoring the levels of neuron , myelin or astroglia specific proteins in the serum and CSF may be a useful approach for evaluating the severity of non traumatic CNS injury.11, 12, 16, 17
Several studies have been published concerning the use of biomarkers in CSF and serum of patients with traumatic brain injury.18, 19, 20, 21 A recent review discussed the role of biomarkers in traumatic brain injury.14 In the field of SCI, however, there is no review on the value of biomarkers.
The aim of this literature review is to describe the current status of neurochemical biomarkers and their potential diagnostic value from either experimental models or patient series of acute SCI. This review focuses on the markers that survey direct structural damage.
Top of pageMethodsClinical and experimental studies that included biomarkers investigating direct structural damage in serum and CSF after an SCI in humans or animals were eligible for this review.
We searched MEDLINE (PubMed interface), EMBASE and reference lists of the included articles published between 1966 and November 2008. In MEDLINE, we used a combination of the following search terms: diagnosis, spinal cord, trauma, biomarker, cerebrospinal fluid Youth Brandon Graham jersey and serum. Furthermore, the references of retrieved publications were checked manually for additional studies that could potentially meet the inclusion criteria.
Top of pageResultsThe search strategy resulted in 250 potentially relevant articles from MEDLINE. The search in other databases yielded no additional relevant articles. A review of the titles, abstract and the full text resulted in the inclusion of 18 articles. Twelve studies investigated biomarkers in humans22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32 and six studies investigated biomarkers in animals.33, 34, 35, 36, 37, 38 Relatively few studies have been performed in which biomarkers in serum and CSF after SCI were investigated. For those that have been conducted, S 100 and neuron specific enolase (NSE) have especially received attention. An overview is shown in Tables 1 and 2. Compared with the control group, the NSE levels in serum and CSF were significantly increased at 6 after the induced SCI. The NSE levels in the two graded injured groups did not differ significantly. Another study simulating ischemic SCI using thoracoabdominal aortic Elite Black Brad Smith jersey cross clamping in 10 dogs identified significantly elevated NSE levels in CSF during clamping and reperfusion.35
Time dependency of biomarkersCao et al.38 evaluated the relationship between the protein levels of NSE and S 100 in serum and CSF and the severity of acute SCI in an animal model. Eighty Sprague rats were divided into four groups: control group, mild SCI group, moderate SCI group and severe SCI group. Graded SCI was provided using a weight drop model from different heights. Serum and CSF samples were collected at different time points. When compared with the control group, the concentrations of NSE and S 100 were significantly (P increased at 2 after SCI and reached maximum levels at 6 The NSE and S 100 levels in the moderate and severe SCI groups were significantly higher (P than the NSE and S 100 levels in the mild SCI group. At 24 after injury, the NSE and S 100 levels in the serum and CSF were still significantly higher than those in the control group. However, after 24 the graded SCI groups did not differ significantly.
It is hypothesized that the peak in the concentration of NSE and S 100 after 6 reflects a mechanical disruption of the spinal cord. Furthermore, the concentration of NSE and S 100 is positively correlated with the grade of the SCI. This study indicates that the NSE and S 100 alterations are time dependent and positively correlated with the severity of the trauma. Although the correlations between the neurophysiological findings and radiographic abnormalities and changes of biomarkers after trauma were not assessed, this study suggests that both biomarkers reflect neuronal and glial damage induced during the acute phase of SCI.
Nerve root injury Although a nerve root compression is not a CNS injury, the role of biomarkers in nerve root injury is addressed. From earlier studies, it is known that a breakdown of the blood barrier occurs in compressed nerve roots.41 This may result in a detectable elevation of biomarkers in CSF.
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