Serum myelin basic protein as a marker of brain injury in aneurysmal subarachnoid haemorrhage.

BACKGROUND: Myelin basic protein (MBP) is the second most abundant protein in central nervous system myelin. Since the 1980s, it has been regarded as a marker of brain tissue injury in both trauma and disease. There have been no recent reports regarding MBP in aneurysmal subarachnoid haemorrhage (SAH). METHODS: One hundred four SAH patients with ruptured aneurysms underwent endovascular treatment within 24 h of rupture, and 156 blood samples were collected: 104 on days 0-3, 32 on days 4-6 and 20 on days 9-12 post-SAH. MBP levels were assayed using ELISA and compared with the clinical status on admission, laboratory results, imaging findings and treatment outcome at 3 months. RESULTS: MBP levels on days 0-3 post-SAH were significantly higher among poor outcome patients (p < 0.001), non-survivors (p = 0.005), patients who underwent intracranial intervention (p < 0.001) and patients with intracerebral haemorrhage (ICH; p < 0.001). On days 4-6 post-SAH, significantly higher levels were found following intracranial intervention (p = 0.009) and ICH (p = 0.039). There was clinically relevant correlation between MBP levels on days 0-3 post-SAH and 3-month Glasgow Outcome Scale (cc = - 0.42) and also ICH volume (cc = 0.48). All patients who made a full recovery had MBP levels below detection limit on days 0-3 post-SAH. Following endovascular aneurysm occlusion, there was no increase in MBP in 86 of the 104 patients investigated (83%). CONCLUSIONS: The concentration of MBP in peripheral blood after intracranial aneurysm rupture reflects the severity of the brain tissue injury (due to surgery or ICH) and correlates with the treatment outcome. Endovascular aneurysm occlusion was not followed by a rise in MBP in most cases, suggesting the safety of this technique.

Predicting mortality in subarachnoid haemorrhage based on first-week routine blood tests.

Accurate prognosis of outcome in subarachnoid haemorrhage (SAH) identifies salvageable poor-grade patients. Widely available and independent prognostic factors are needed, thus value of six routine blood tests is established. Prospectively collected database of 116 aneurysmal SAH patients was reviewed for white blood cell (WBC) count and concentration of C-reactive protein (CRP), sodium, potassium, glucose and haemoglobin on day 0, 1, 2, 3-4 and 5-7 post-SAH. All patients were admitted within 24 h, treated endovascularly within 48 h and assessed neurologically at admission and at three months post-SAH. Multivariate logistic regression and receiver operating curve were analyzed for each type of parameter assessed on specific day post-SAH. We have identified three different types of blood tests with the largest area under the curve (AUC). The three types of parameters identified as the most accurate, independent prognostic factors for mortality are WBC count on day 1 (p < 0.01 with AUC of 0.82); sodium level on day 2 (p < 0.05 with AUC of 0.81) and CRP level on day 3-4 (p < 0.05 with AUC of 0.74). Cut-off values of 12.88 × 103/µl, 155 mmol/l and 142.7 mg/l (respectively) exceeded on indicated time points predict patient's death with 96.7% specificity and 68.8% sensitivity. Early alterations in routine blood tests provide an accurate prognosis of death in SAH independently from well-established prognostic tools.

Clusterin, a New Cerebrospinal Fluid Biomarker in Severe Subarachnoid Hemorrhage: A Pilot Study.

BACKGROUND: Inflammation following subarachnoid hemorrhage (SAH) involves numerous mediators with biomarker properties. Preliminary studies indicated that clusterin, a multifunctional chaperon protein, was a potential biomarker in SAH. We aimed to clarify the status of clusterin in SAH. METHODS: From 27 patients with severe SAH, 47 cerebrospinal fluid (CSF) samples were collected 0-3, 5-7, and 10-14 days after SAH. Control CSF was collected from 25 age- and sex-matched healthy control subjects undergoing spinal anesthesia for minor surgery. Clusterin concentrations were assayed using enzyme-linked immunosorbent assay and compared with inflammatory markers, imaging findings, and treatment outcome. RESULTS: In healthy control subjects, mean CSF clusterin level (1908.5 ng/mL ± 36.0) was significantly higher than in the patient group (P < 0.001). In the patient group, mean clusterin level was 741.1 ng/mL ± 759.2 0-3 days, 601.6 ng/mL ± 507.2 5-7 days, and 639.2 ng/mL ± 446.8 10-14 days after SAH. Clusterin level failed to differentiate between good (Glasgow Outcome Scale 4-5) and poor (Glasgow Outcome Scale 1-3) outcomes 0-3 days and 10-14 days after SAH (P = 0.238 and P = 0.225), but significantly higher levels of CSF clusterin were found 5-7 days after SAH in patients with good outcome (P = 0.017). There was a significant correlation between CSF clusterin level 5-7 days after SAH and Glasgow Outcome Scale at 3 months (correlation coefficient = 0.633). The best correlation was found for World Federation of Neurological Societies scale (correlation coefficient = -0.741). CONCLUSIONS: SAH is associated with immediate decrease in CSF clusterin concentrations. Clusterin level at one point was a good predictor of outcome, and it may serve as a biomarker.

Increase of Soluble RAGE in Cerebrospinal Fluid following Subarachnoid Haemorrhage.

Receptors for advanced glycation end-products (RAGE) mediate the inflammatory reaction that follows aneurysmal subarachnoid haemorrhage. Soluble RAGE (sRAGE) may function as a decoy receptor. The significance of this endogenous anti-inflammatory mechanism in subarachnoid haemorrhage (SAH) remains unknown. The present study aims to analyse sRAGE levels in the cerebrospinal fluid (CSF) of SAH patients. sRAGE levels were assayed by ELISA kit in 47 CSF samples collected on post-SAH days 0-3, 5-7, and 10-14 from 27 SAH patients with acute hydrocephalus. CSF levels of sRAGE were compared with a control group and correlated with other monitored parameters. In the control group, the CSF contained only a trace amount of sRAGE. By contrast, the CSF of 20 SAH patients collected on post-SAH days 0-3 was found to contain statistically significant higher levels of sRAGE (mean concentration 3.91 pg/mL, p < 0.001). The most pronounced difference in CSF sRAGE levels between good and poor outcome patients was found on days 0-3 post-SAH but did not reach the significance threshold (p = 0.234). CSF sRAGE levels did not change significantly during hospitalisation (p = 0.868) and correlated poorly with treatment outcome, systemic inflammatory markers, and other monitored parameters. Our study revealed an early and constant increase of sRAGE level in the CSF of SAH patients.

Original Protocol Using Computed Tomographic Angiography for Diagnosis of Brain Death: A Better Alternative to Standard Two-Phase Technique?

BACKGROUND The application of computed tomographic angiography (CTA) for the diagnosis of brain death (BD) is limited because of the low sensitivity of the commonly used two-phase method consisting of assessing arterial and venous opacification at the 60th second after contrast injection. The hypothesis was that a reduction in the scanning delay might increase the sensitivity of the test. Therefore, an original technique using CTA was introduced and compared with catheter angiography as a reference. MATERIAL AND METHODS In a prospective multicenter trial, 84 clinically brain-dead patients were examined using CTA and catheter angiography. The sensitivities of original CTA technique, involving an arterial assessment at the 25th second and a venous assessment at the 40th second, and the standard CTA, involving an arterial and venous assessment at the 60th second, were compared to catheter angiography. RESULTS Catheter angiography results were consistent with the clinical diagnosis of BD in all cases. In comparison to catheter angiography, the sensitivity of original CTA technique was 0.93 (95%CI, 0.85-0.97; p<0.001) and 0.57 (95%CI, 0.46-0.68; p<0.001) for the standard protocol. The differences were statistically significant (p=0.03 for original CTA and p<0.001 for standard CTA). Decompressive craniectomy predisposes to a false-negative CTA result with a relative risk of 3.29 (95% CI, 1.76-5.81; p<0.001). CONCLUSIONS Our original technique using CTA for the assessment of the cerebral arteries during the arterial phase and the deep cerebral veins with a delay of 15 seconds is a highly sensitive test for the diagnosis of BD. This method may be a better alternative to the commonly used technique.