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.

CSF Proteomics of Patients with Hydrocephalus and Subarachnoid Haemorrhage.

BACKGROUND: The pathophysiology of brain injury following aneurysmal subarachnoid haemorrhage (SAH) is associated with numerous mediators. The aim of the study is to analyse protein changes after SAH in cerebrospinal fluid (CSF) using mass spectrometry (MS). METHODS: CSF samples were obtained from forty-four control subjects, seven good outcome and ten poor outcome SAH patients. CSF samples were collected at specific time intervals after SAH (days 1, 5 and 10). MALDI-TOF (Matrix Assisted Laser Desorption/Ionization Time-of-Flight) and ClinProTools software were utilised for MS, MS/MS (Mass Spectrometry) spectra collection and analysis. Selected masses were identified. The MALDI-TOF profiling experiments allowed for the targeted selection of potential markers in SAH. The study was performed in three steps by comparison of CSF samples: (1) from the control group and SAH patients (both good and poor outcome groups); (2) collected on days 1, 5 and 10 within the groups of poor SAH and good SAH patients, respectively; (3) from poor outcome SAH and good outcome patients at days 1, 5 and 10. RESULTS: 15 new proteins whose CSF level is alternated by SAH presence, SAH treatment outcome and time passed since aneurysm rupture were identified. CONCLUSIONS: We demonstrated new proteins which might play a role in different stages of subarachnoid haemorrhage and could be a new target for further investigation.

Occipitocervical Fusion: An Updated Review.

Occipitocervical fusion (OCF) is indicated for instability at the craniocervical junction (CCJ). Numerous surgical techniques, which evolved over 90 years, as well as unique anatomic and kinematic relationships of this region present a challenge to the neurosurgeon. The current standard involves internal rigid fixation by polyaxial screws in cervical spine, contoured rods and occipital plate. Such approach precludes the need of postoperative external stabilization, lesser number of involved spinal segments, and provides 95-100% fusion rates. New surgical techniques such as occipital condyle screw or transarticular occipito-condylar screws address limitations of occipital fixation such as variable lateral occipital bone thickness and dural sinus anatomy. As the C0-C1-C2 complex is the most mobile portion of the cervical spine (40% of flexion-extension, 60% of rotation and 10% of lateral bending) stabilization leads to substantial reduction of neck movements. Preoperative assessment of vertebral artery anatomical variations and feasibility of screw insertion as well as visualization with intraoperative fluoroscopy are necessary. Placement of structural and supplemental bone graft around the decorticated bony elements is an essential step of every OCF procedure as the ultimate goal of stabilization with implants is to provide immobilization until bony fusion can develop.

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.

Corrigendum: Amino Acids in Cerebrospinal Fluid of Patients With Aneurysmal Subarachnoid Haemorrhage: An Observational Study.

[This corrects the article on p. 438 in vol. 8, PMID: 28894433.].

Amino Acids in Cerebrospinal Fluid of Patients with Aneurysmal Subarachnoid Haemorrhage: An Observational Study.

BACKGROUND: The authors are aware of only one article investigating amino acid concentrations in cerebrospinal fluid (CSF) in patients with ruptured intracranial aneurysms, and this was published 31 years ago. Since then, both management of subarachnoid haemorrhage (SAH) and amino acid assay techniques have seen radical alterations, yet the pathophysiology of SAH remains unclear. OBJECTIVE: To analyse the pattern of concentrations of amino acids and related compounds in patients with different outcomes following aneurysmal SAH. METHODS: 49 CSF samples were collected from 23 patients on days 0-3, 5, and 10 post-SAH. Concentrations of 33 amino acids and related compounds were assayed by liquid chromatography tandem mass spectrometry in patients with good [Glasgow Outcome Scale (GOS) 1-3] and poor (GOS 4-5) outcome. RESULTS: Of the 33 compounds assayed, only hydroxyproline and 3-aminoisobutyric acid appeared not to increase significantly following SAH. In poor outcome patients, we found significantly higher concentrations of aspartic acid (p = 0.038), glutamic acid (p = 0.038), and seven other compounds on days 0-3 post-SAH; glutamic acid (p = 0.041) on day 5 post-SAH, and 2-aminoadipic acid (p = 0.033) on day 10 post-SAH. The most significant correlation with GOS at 3 months was found for aminoadipic acid on day 10 post-SAH (cc = -0.81). CONCLUSION: Aneurysmal rupture leads to a generalised increase of amino acids and related compounds in CSF. The patterns differ between good and poor outcome cases. Increased excitatory amino acids are strongly indicative of poor outcome.

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.

Correction: Soluble Toll-Like Receptors 2 and 4 in Cerebrospinal Fluid of Patients with Acute Hydrocephalus following Aneurysmal Subarachnoid Haemorrhage.

[This corrects the article DOI: 10.1371/journal.pone.0156171.].

Soluble Toll-Like Receptors 2 and 4 in Cerebrospinal Fluid of Patients with Acute Hydrocephalus following Aneurysmal Subarachnoid Haemorrhage.

BACKGROUND: Toll-like receptor (TLR) signalling begins early in subarachnoid haemorrhage (SAH), and plays a key role in inflammation following cerebral aneurysm rupture. Available studies suggest significance of endogenous first-line blockers of a TLR pathway-soluble TLR2 and 4. METHODS: Eighteen patients with SAH and acute hydrocephalus underwent endovascular coiling and ventriculostomy; sTLR2 and 4 levels were assayed in cerebrospinal fluid (CSF) collected on post-SAH days 0-3, 5, and 10-12. Release kinetics were defined. CSF levels of sTLR2 and 4 were compared with a control group and correlated with the clinical status on admission, the findings on imaging, the degree of systemic inflammation and the outcome following treatment. RESULTS: None of study group showed detectable levels of sTLR2 and 4 on post-SAH day 0-3. 13 patients showed increased levels in subsequent samples. In five SAH patients sTLR2 and 4 levels remained undetectable; no distinctive features of this group were found. On post-SAH day 5 the strongest correlation was found between sTLR2 level and haemoglobin level on admission (cc = -0.498, P = 0.037). On post-SAH day 10-12 the strongest correlation was revealed between sTLR2 and treatment outcome (cc = -0.501, P = 0.076). Remaining correlations with treatment outcome, status at admission, imaging findings and inflammatory markers on post-SAH day 5 and 10-12 were negligible or low (-0.5 ≤ cc ≤ 0.5). CONCLUSIONS: In the majority of cases, rupture of a cerebral aneurysm leads to delayed release of soluble TLR forms into CSF. sTLR2 and 4 seem to have minor role in human post-SAH inflammation due to delayed release kinetics and low levels of these protein.

HMGB1 Level in Cerebrospinal Fluid as a Marker of Treatment Outcome in Patients with Acute Hydrocephalus Following Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Attempts to clarify mechanisms of early brain injury in subarachnoid hemorrhage (SAH) revealed a high-mobility group box 1 (HMGB1) protein involvement in sterile inflammation initiated by aneurysm rupture. This study aims at assessing the prognostic value of HMGB1 in comparison with traditional biomarkers. METHODS: Ten patients with Fisher grade 4 SAH and acute hydrocephalus underwent endovascular coiling and ventriculostomy. HMGB1 level was measured in cerebrospinal fluid (CSF) samples collected on first, fifth, and 10th day. HMGB1 level in first sample was correlated with treatment outcome assessed in Glasgow outcome scale (GOS) at 3 months. Obtained results were compared with plasma inflammatory markers, clinical grading scales, and imaging grading scales. HMGB1 level in consecutive samples was analyzed in search of concentration trends correlating with patients' outcome. RESULTS: HMGB1 level in CSF of SAH patients, in contrast to control group, is significantly elevated (P < .001). Good (GOS > 3) and poor (GOS ≤ 3) outcome patients differ significantly in HMGB1 level on admission (P < .01). The strongest correlation to patients' outcome was found for Hunt and Hess scale (R = -.887, P < .01), HMGB1 level (R = -.859, P < .01), and World Federation of Neurological Surgeons scale (R = -.832, P < .01). Constant and high HMGB1 level of 10 ng/mL or more in consecutive CSF samples identifies nonsurvivors. CONCLUSIONS: HMGB1 protein is elevated in SAH patients. Changes in the concentration of HMGB1 in consecutive samples of the CSF correlate with outcome. Our results encourage further proteomic investigation.

Very late in-stent thrombosis 9 years after double stent treatment of fusiform basilar artery aneurysm.

Endovascular treatment seems to be the best approach to posterior circulation fusiform aneurysms. Double stent techniques are frequently used to occlude basilar artery dilations. Unfortunately, there is a limited number of studies that have followed up with patients over prolonged periods of time in order to evaluate delayed complications, such as stenosis, thrombosis or migration of stents. We present an unusual case of in-stent thrombosis 9 years after basilar artery aneurysm treatment to caution about complications associated with double stent implantation.

Extracranial Internal Carotid Artery Dissection Treated with Self-expandable Stents: A Single-Centre Experience.

PURPOSE: Treatment of choice for the internal carotid artery dissection (ICAD) is anticoagulation for three to 6 months. Endovascular procedures may be a promising alternative for patients (pts) with haemodynamic impairment, recurrent ischaemic symptoms or symptomatic pseudoaneurysms. Thus, the purpose of this study was to evaluate the efficacy and safety of carotid artery stenting in treatment of selected pts with extracranial ICAD. METHODS: This study involved 18 symptomatic pts with the mean age of 44.6 ± 10.4 years with ICAD treated with the use of self-expandable stents. Six months after primary procedures, pts were readmitted to hospital and physical examination followed by cerebral angiography was performed. In the late follow-up period, clinical evaluations completed by duplex Doppler ultrasonography were carried out every 6 months and at the end of the follow-up period. RESULTS: Nobody died and no life-threatening adverse events were observed during either the in-hospital stay or post-discharge follow-up period (median 21 months). Stent deployment immediately restored flow in the true lumen of ICA in all cases. However, residual blood flow through the false lumen was observed in one pt. Complete resolution of clinical symptoms was observed in 14 pts (78%), partial improvement in 2 (11%) and persistence of neurological deficit in 2 (11%). CONCLUSIONS: Implantation of self-expandable stents in treatment of selected extracranial ICAD cases is safe. This method may enable us to restore immediately and usually permanently proper arterial blood flow in the ICA and in consequence lead to significant clinical improvement in the late follow-up period.