Evaluation of S-100b as a specific marker for neuronal damage due to minor head trauma.
ABSTRACT Management of patients with minor head trauma (MHT) continues to be debated in the literature. Measurement of S-100b in serum has been introduced into the discussion as an additional screening tool for intracerebral injuries because routine cranial computed tomography (CCT) of a large number of patients causes logistic difficulties, and the neurologic examination is often impaired by a high frequency of coincidental intoxication. The aim of our study was to determine the diagnostic value of measuring S-100b in the serum of MHT patients to identify risk groups. Additional validity should be aquired by a comparison with plasma levels of polymorphonuclear neutrophil (PMN) elastase an established general trauma marker. A series of 52 patients with MHT were included in the prospective study. At admission the patients underwent a routine CCT scan to detect intracerebral lesions, and blood samples were drawn to investigate circulating levels of S-100b and PMN elastase. For comparison, data for a positive control group of 10 severe head trauma patients (initial Glasgow Coma Scale score < 8) and for a negative control group with 20 healthy volunteers were obtained. The interval between MHT and admission to our hospital was 73.4 +/- 47.0 minutes. The initial S-100b serum levels of MHT patients were 0.470 +/- 0.099 ng/ml, those of the positive control group were 7.16 +/- 3.77 ng/ml, and those of the negative control group were 0.05 +/- 0.01 ng/ml. Relevant pathologic CCT scans were detected in 28.8% of MHT patients; one patient of that group was subjected to immediate surgical intervention (1.9%). At a cut-off point of 0.1 ng/ml, the sensitivity of positive S-100b levels reached 100% and the specificity 40.5%. Plasma levels of PMN elastase reached 60.52 +/- 10.75 ng/ml in the MHT group, 66.4 +/- 14.92 ng/ml in the severely head-injured group, and 23.26 +/- 1.53 ng/ml in the negative control group. Serum levels of S-100b seem to be a highly sensitive but not very specific marker for isolated neurotrauma. Measurement of this parameter may be helpful as an additional screening tool to identify high risk groups in the cohort of MHT patients.
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ABSTRACT: Brain–specific proteins (BSP) are each relatively specific for particular cell–types within the nervous system. The BSP studied were glial fibrillary acidic protein (GFAP) and S100B for the astrocyte, ferritin for microglia and neurofilaments (Nf) for the axon. BSP are released into the extracellular fluid (ECF) following cellular destruction and during phases of high cellular activity such as astrocytic or microglial activation. ECF BSP equilibrate with those in the cerebrospinal fluid (CSF). This allows us to quantify BSP from the CSF and estimate the overall average of axonal damage (CSF Nf), astrocytic and microglia activation (respectively CSF S100B, CSF ferritin) and astrogliosis (CSF GFAP). New enzyme linked immunoabsorbant assays (ELISA) have been developed for measuring Nf and GFAP in the CSF. Previously established ELISAs have been used to measure S100B and ferritin. It has been shown that spinal cord atrophy in a mouse model of autoimmune encephalomyelitis (EAE) was paralleled by a decrease of Nf indicating loss of axons, and an increase in GFAP indicating astrogliosis. These findings have been confirmed and extended in a human post–mortem study where BSP levels were quantified in multiple sclerosis (MS) lesions of different age and activity. S100B and Nf were associated with acute lesions, ferritin was elevated in all lesion types, while GFAP was increased in both acute and chronic lesions. CSF BSP levels were then quantified in a cross–sectional study of MS patients with the aim of distinguishing clinical subgroups, such as relapsing remitting (RR), primary progressive (PP) and secondary progressive (SP) disease. In addition an attempt was made to relate CSF BSP levels to grades of disability using clinical scales including Kurtzke’s EDSS, an ambulation index (AI) and the 9–hole PEG test (9HPT). It was shown that CSF S100B was higher in RR MS while CSF ferritin was elevated in PP MS patients. The S100B:ferritin ratio emphasised the distinction between the MS subtypes. CSF GFAP was higher in poorly ambulating (AI) and severely disabled (EDSS) patients. CSF GFAP correlated with the EDSS in SP MS patients. This suggests that gliosis is an important feature in SP MS. CSF Nf levels were quantified in a longitudinal study at baseline and at 3–year follow–up. It was shown that more SP/PP than RR MS patients experienced an increase in CSF Nf levels over this time, suggesting cumulative axonal damage in this subgroup. RR MS patients who had elevated CSF Nf levels at baseline had a worse clinical course, suggesting that initial high CSF Nf levels in RR MS patients are a poor prognostic sign. CSF Nf levels at follow–up correlated with the EDSS, AI and 9HPT suggesting that axonal pathology in MS is a dynamic process possibly balancing features of de- and regenerative activities.
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ABSTRACT: S100B, established as prevalent protein of the central nervous system, is a peripheral biomarker for blood-brain barrier disruption and often also a marker of brain injury. However, reports of extracranial sources of S100B, especially from adipose tissue, may confound its interpretation in the clinical setting. The objective of this study was to characterize the tissue specificity of S100B and assess how extracranial sources of S100B affect serum levels. The extracranial sources of S100B were determined by analyzing nine different types of human tissues by ELISA and Western blot. In addition, brain and adipose tissue were further analyzed by mass spectrometry. A study of 200 subjects was undertaken to determine the relationship between body mass index (BMI) and S100B serum levels. We also measured the levels of S100B homo- and heterodimers in serum quantitatively after blood-brain barrier disruption. Analysis of human tissues by ELISA and Western blot revealed variable levels of S100B expression. By ELISA, brain tissue expressed the highest S100B levels. Similarly, Western blot measurements revealed that brain tissue expressed high levels of S100B but comparable levels were found in skeletal muscle. Mass spectrometry of brain and adipose tissue confirmed the presence of S100B but also revealed the presence of S100A1. The analysis of 200 subjects revealed no statistically significant relationship between BMI and S100B levels. The main species of S100B released from the brain was the B-B homodimer. Our results show that extracranial sources of S100B do not affect serum levels. Thus, the diagnostic value of S100B and its negative predictive value in neurological diseases in intact subjects (without traumatic brain or bodily injury from accident or surgery) are not compromised in the clinical setting.PLoS ONE 09/2010; 5(9). DOI:10.1371/journal.pone.0012691 · 3.53 Impact Factor
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ABSTRACT: S100B is a calcium-binding protein that is produced primarily by astrocytes. Increased serum S100B protein levels reflect neurological damage. Autoimmunity may have a role in the pathogenesis of autism in some patients. Autoantibodies may cross the blood-brain barrier and combine with brain tissue antigens, forming immune complexes and resulting in neurological damage. We are the first to investigate the relationship between serum levels of S100B protein, a marker of neuronal damage, and antiribosomal P protein antibodies in autistic children. Serum S100B protein and antiribosomal P antibodies were measured in 64 autistic children in comparison to 46 matched healthy children. Autistic children had significantly higher serum S100B protein levels than healthy controls (P < 0.001). Children with severe autism had significantly higher serum S100B protein than patients with mild to moderate autism (P = 0.01). Increased serum levels of antiribosomal P antibodies were found in 40.6% of autistic children. There were no significant correlations between serum levels of S100B protein and antiribosomal P antibodies (P = 0.29). S100B protein levels were elevated in autistic children and significantly correlated to autistic severity. This may indicate the presence of an underlying neuropathological condition in autistic patients. Antiribosomal P antibodies may not be a possible contributing factor to the elevated serum levels of S100B protein in some autistic children. However, further research is warranted to investigate the possible link between serum S100B protein levels and other autoantibodies, which are possible indicators of autoimmunity to central nervous system in autism.Journal of Neuroinflammation 03/2012; 9(1):54. DOI:10.1186/1742-2094-9-54 · 4.90 Impact Factor