A 46-year old gentleman was admitted to hospital after having been found unconscious in his home. Past medical history included malignant melanoma that had been radically excised 9 years previously and the patient, after several controls, was believed to be in remission. There was no record of excessive alcohol- or other drug abuse.
On admission the patient presented with a Glasgow Coma Score (GCS) of 3, a dilated left pupil, bilaterally brisk reflexes, and positive Babinski sign. There were no signs of neck stiffness, fever, petechiae, or trauma. S-100B was not acquired on admission (Figure 1). A CT scan showed a left-sided chronic subdural hemorrhage (SDH), resulting in a midline shift of 15 mm (Figure 2).
Evacuation of the subdural hematoma was performed. Intra-operatively, the pressure within the hematoma was noted to be low. The brain parenchyma failed to resume its natural position after the evacuation. The first S-100B sample was obtained post-operatively 4 h and 22 min after the paramedics were alerted. S-100B was elevated (1.9 mug/l; Figure 1). The patient did not respond as well as is expected after an SDH evacuation. A follow-up CT scan on day 2 revealed a persistent midline-shift, as well as new occipital infarcts, assumed to be secondary to cerebral herniation.
The patient improved to a GCS of 9 (E1 + M6 + V2; E, Eye; M, Motor response; V, Voice) on day 2. On day 4, the patient deteriorated, GCS 6 (E1 + M4 + V1). A CT scan revealed an increased midline-shift, so a re-evacuation was performed later the same day and an intra-cranial pressure (ICP) monitor (Codman ) was inserted. The dura was thicker than normal and the subdural mass did not look like a conventional hematoma, so samples were acquired for further pathological examination. Post-operatively the patient demonstrated a refractory critically unstable ICP ranging 15-30 mmHg and an increasing midline-shift on CT scan. Therapeutic management included hyperosmotic fluid, deep sedation with Midazolam, Morphine and Propofol, and hypothermia therapy. To facilitate treatment an external ventricular drain (EVD) was inserted. The S-100B levels were followed twice a day and showed an unusual peak of 22 mug/l (normal range <0.11 mug/l) on day 5 (Figure 1).
Other sources of the extreme S-100B levels, including encephalitis, new cerebral infarctions, and extra-cerebral sources such as malignant melanoma, were pursued. Further head CT scans, including CT-angiography, showed no new findings. An EEG did not show any epileptic activity, MRI confirmed multiple infarcts, more than previously detected (Figure 3) yet no other information regarding the dura. A CT scan of thorax and abdomen showed widespread lung and liver metastases (not shown). Later day 5, a decompressive left-sided hemicraniectomy was performed (Figure 1, point E).
While the S-100B declined post-operatively, the patient's ICP was still refractory unstable and the midline-shift remained 15-16 mm (Figure 4). Despite optimized neurosurgical intensive care, the patient showed steadily increasing ICP so treatment was finally withdrawn. The patient passed away on day 8 of his hospital stay due to brain herniation.
The pathologist reported that extensive granulomatous tissue was noted within the hematoma and dura during the re-evacuation. The histopathological examination showed cells positive for S-100, Melan A, and HMB45, making metastases of malignant melanoma most probable. An autopsy confirmed malignant melanoma metastasis within the lungs, pleura, and lymphatic system. Metastatic tumor growth was also found in the brain parenchyma, dura, gallbladder, and kidneys.
The protein S-100B is an increasingly used biomarker within neurosurgery and neurointensive care. The calcium-binding protein, which is synthesized and released by cells mainly found in the CNS (Moore,), is primarily an astrocytic protein but is also located in other cells of the CNS, such as neurons, oligodendrocytes, and choroid plexus epithelium (Steiner et al.,).
Both serum and CSF S-100B have been proposed to be valuable biomarkers of traumatic brain injury (TBI; Herrmann et al.,). In the early process, S-100B can help estimate the extent of the primary injury (Herrmann et al.,; Savola et al.,), monitor potential secondary insults (Raabe et al.,; Bellander et al.,) and be an asset in outcome prediction (Herrmann et al.,; Savola et al.,; Thelin et al., submitted).
Increased S-100B levels have also been found in patients suffering from ischemic cerebrovascular insults (Jonsson et al.,; Foerch et al.,). Vasospasm and long-term outcome in subarachnoid hemorrhages have been shown to correlate to increased levels of S-100B (Oertel et al.,). CNS infections may alter S-100B levels such as viral and bacterial meningoencephalitis and neuroborreliosis (Lins et al.,) and herpes simplex encephalitis (Studahl et al.,).
Clinically, S-100B is also the most widely used biomarker in malignant melanoma patients (Smit et al.,). The main use is monitoring of advance disease, staining of histopathological samples and to evaluate the efficacy of therapy (Martenson et al.,; Smit et al.,; Egberts et al.,).
Serum samples of S-100B were obtained on admission to Karolinska University Hospital and approximately every 12 h (06:00 and 18:00). All serum samples were arterial and analyzed using an automatic electro-chemiluminescence immunoassay (Elecsys S-100B ; Roche Diagnostics, Penzberg, Germany) method. The serum levels of S-100B and NSE, and radiological findings, were acquired using the medical files from the hospital database system Take Care  (CompuGroup Medical Sweden AB, Farsta, Sweden). The ICP was acquired using ICU-Pilot  (Dipylon Medical, Solna, Sweden).