Role of S100
S100 proteins are a family of small, dimeric multigenic calcium-binding proteins comprising various combinations of α and β subunits. S100 proteins most commonly occur as S100A (α - α) or S100B (α - β [S100A1B] and β - β [S100BB]) subtypes. S100B is predominately confined to glial and Schwann cells and is the most well-studied subtype in TBI*. Both S100A1B and S100BB have been implicated in severe TBI.
Severe TBI invariably results in neuronal destruction and destabilization of the blood–brain barrier (BBB). These phenomena are accompanied by a release of S100B protein into the blood. S100B is measurable within minutes of a TBI, and can be detected for an extended period in the bloodstream. S100B is removed from the serum by the renal clearance pathway, with a half-life of 20 to 25 minutes.
A schematic representation of the blood-brain barrier (BBB) (adapted from Deetjen/Speckmann: Physiologie; München 1992; S100 added).
*Lower concentrations of S100 have been observed in chondrocytes, melanocytes, muscle tissue, and adipocytes.
- S100B testing can help determine which low-risk patients with minor head injury do not need a CT
A CT scan has high sensitivity for detecting intracranial injuries in patients with head injury. However, the technique is costly, exposes the patient to high doses of radiation, and clinically relevant lesions are found in less than 10% of cases of minor head injury. Several studies have demonstrated that a normal S100B level reliably predicts normal CT findings after minor head injury in adults.
Serum S100B increases almost immediately after a relevant brain injury, due to a brief breach of the blood–brain barrier. The best results for clinical use of S100B is in the field of minor head injuries. Due to the high specificity and high negative predictive value for neurosurgically relevant intracranial complications, it has been estimated that S100B could reduce the frequency of head CT by 30%, and still maintain patient safety.
The Scandinavian guidelines recommend that adult patients after mild head injury with GCS 14 and no risk factors (anticoagulant therapy or coagulation disorders, post-traumatic seizures, clinical signs of depressed or basal skull fracture, focal neurological deficits), or GCS 15 with loss of consciousness or repeated (≥2) vomiting and no other risk factors, can be sampled for analysis of S100B if less than 6 h have elapsed following trauma. If S100B is less than 0.10 μg/l, the patient may be discharged without a CT (moderate quality, strong recommendation). The evidence was initially of high quality.
- S100 levels predict short-, medium-, and long-term patient outcome
S100B is related to outcome prognosis. Serial measurement of S100B accurately predicts short-term mortality, with the strongest correlation with clinical outcome seen >84 hours after trauma.18 Comparison of time courses of S100B levels in patients with favorable and unfavorable outcomes also indicate that S100B values by day 2 after admission independently predict 12-month mortality.
- Monitoring progression of severe TBI with S100 assays
S100B protein is a marker that displays high clinical sensitivity for severe TBI, and the extent of S100B elevation has been found to be useful in predicting clinical outcome after brain injury.
- S100B levels correlate with the severity of brain damage
S100B concentrations in serum have been shown to be representative of the extent of primary brain damage, as corroborated by clinical scales of neurological status, subsequent CT examination, and neurological outcome.
- S100 levels may indicate secondary neurological deterioration in patients with severe TBI
Secondary neurological events are accompanied by an elevation in the serum levels of S100B, often visible earlier than when detected with diagnostic imaging. S100B levels have been shown to rise hours to days before changes in intracranial pressure or onset of cerebral hypoxia. S100B levels may be used to monitor comatose intensive care patients for neurological complications such as a new infarction, new hemorrhage, or a newly developed progressive disease.
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