Relationship of vascular wall tension and autoregulation following traumatic brain injury.

BACKGROUND: The vascular wall tension (WT) of small cerebral vessels can be quantitatively estimated through the concept of critical closing pressure (CrCP), which denotes the lower limit of arterial blood pressure (ABP), below which small cerebral arterial vessels collapse and blood flow ceases. WT can be expressed as the difference between CrCP and intracranial pressure (ICP) and represent active vasomotor tone. In this study, we investigated the association of WT and CrCP with autoregulation and outcome of a large group of patients after traumatic brain injury (TBI). METHODS: We retrospectively analysed recordings of ABP, ICP and transcranial Doppler (TCD) blood flow velocity from 280 TBI patients (median age: 29 years; interquartile range: 20-43). CrCP and WT were calculated using the cerebrovascular impedance methodology. Autoregulation was assessed based on TCD-based indices, Mx and ARI. RESULTS: Low values of WT were found to be associated with an impaired autoregulatory capacity, signified by its correlation to FV-based indices Mx (R = -0.138; p = 0.021) and ARI (R = 0.118; p = 0.048). No relationship could be established between CrCP and any of the autoregulatory indices. Neither CrCP nor WT was found to correlate with outcome. CONCLUSIONS: Impaired autoregulation was found to be associated with a lower WT supporting the role of vasoparalysis in the loss of autoregulatory capacity. In contrast, no links between CrCP and autoregulation could be identified.

Prognostic significance of IL-8-STAT-3 pathway in astrocytomas: correlation with IL-6, VEGF and microvessel morphometry.

Malignant astrocytomas are highly vascular neoplasms characterized by a potent angiogenic and immunosuppressive phenotype. Th2-cytokines (IL-6/IL-8) are implicated as major regulators of glioma cell growth and invasiveness. STAT-3, a downstream transducer of cytokine signaling is positively associated with tumor angiogenesis. The present study aimed to investigate the expression of IL-8 and p-STAT-3 in 97 diffusely infiltrating astrocytomas of various grades, in relation to IL-6, VEGF, clinicopathological features, microvascular characteristics and patients' survival. IL-8 expression was localized in neoplastic cells, being associated with p-STAT-3 (p = 0.0013), IL-6 (p = 0.0004) and VEGF (p < 0.0001) around areas of necrosis as well as in perivascular inflammatory and endothelial cells. All the molecules under study correlated with tumor grade and degree of necrosis (p < 0.05, respectively). p-STAT-3, IL-8 and VEGF expression was positively associated with microvessel density (p = 0.0491, p < 0.0001 and p = 0.0118, respectively). Univariate analysis indicated that overexpression of IL-8 and IL-6 adversely affected survival in the entire cohort whereas increased p-STAT-3 expression was predictive of improved survival in high grade (III/IV) astrocytomas (p = 0.0032). In multivariate analysis only IL-8 expression (p = 0.043) retained its significance. The prognostic significance of IL-8 expression and its correlation with p-STAT-3 and VEGF implicates this novel signaling pathway in astroglial tumors progression providing new targets for effective immunotherapy.

A noninvasive estimation of cerebral perfusion pressure using critical closing pressure.

OBJECT: Cerebral blood flow is associated with cerebral perfusion pressure (CPP), which is clinically monitored through arterial blood pressure (ABP) and invasive measurements of intracranial pressure (ICP). Based on critical closing pressure (CrCP), the authors introduce a novel method for a noninvasive estimator of CPP (eCPP). METHODS: Data from 280 head-injured patients with ABP, ICP, and transcranial Doppler ultrasonography measurements were retrospectively examined. CrCP was calculated with a noninvasive version of the cerebrovascular impedance method. The eCPP was refined with a predictive regression model of CrCP-based estimation of ICP from known ICP using data from 232 patients, and validated with data from the remaining 48 patients. RESULTS: Cohort analysis showed eCPP to be correlated with measured CPP (R = 0.851, p < 0.001), with a mean ± SD difference of 4.02 ± 6.01 mm Hg, and 83.3% of the cases with an estimation error below 10 mm Hg. eCPP accurately predicted low CPP (< 70 mm Hg) with an area under the curve of 0.913 (95% CI 0.883-0.944). When each recording session of a patient was assessed individually, eCPP could predict CPP with a 95% CI of the SD for estimating CPP between multiple recording sessions of 1.89-5.01 mm Hg. CONCLUSIONS: Overall, CrCP-based eCPP was strongly correlated with invasive CPP, with sensitivity and specificity for detection of low CPP that show promise for clinical use.

Cerebral vasospasm affects arterial critical closing pressure.

The effect of cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage (SAH) on critical closing pressure (CrCP) has not been fully delineated. Using cerebral impedance methodology, we sought to assess the behavior of CrCP during CVS. As CrCP expresses the sum of intracranial pressure (ICP) and vascular wall tension, we also explored its role in reflecting changes in vascular tone occurring in small vessels distal to spasm. This retrospective analysis was performed using recordings from 52 patients, diagnosed with CVS through transcranial Doppler measurements. Critical closing pressure was calculated noninvasively using arterial blood pressure and blood flow velocity. Outcome was assessed at both discharge and 3 months after ictus with the Glasgow Outcome Scale. The onset of CVS caused significant decreases in CrCP (P=0.025), without any observed significant changes in ICP (P=0.134). Vasospasm induced asymmetry, with CrCP ipsilateral to CVS becoming significantly lower than contralateral (P=0.025). Unfavorable outcomes were associated with a significantly lower CrCP after the onset of CVS (discharge: P=0.014; 3 months after SAH: P=0.020). Critical closing pressure is reduced in the presence of CVS in both temporal and spatial assessments. As ICP remained unchanged during CVS, reduced CrCP most probably reflects a lower wall tension in dilated small vessels distal to spasm.

Complex interactions between the components of the PI3K/AKT/mTOR pathway, and with components of MAPK, JAK/STAT and Notch-1 pathways, indicate their involvement in meningioma development.

We investigated the significance of PI3K/AKT/mTOR pathway and its interactions with MAPK, JAK/STAT and Notch pathways in meningioma progression. Paraffin-embedded tissue from 108 meningioma patients was analysed for the presence of mutations in PIK3CA and AKT1. These were correlated with the expression status of components of the PI3K/AKT/mTOR pathway, including p85α and p110γ subunits of PI3K, phosphorylated (p)-AKT, p-mTOR, p-p70S6K and p-4E-BP1, as well as of p-ERK1/2, p-STAT3 and Notch-1, clinicopathological data and patient survival. A mutation in PIK3CA or AKT1 was found in around 9 % of the cases. Higher grade meningiomas displayed higher nuclear expression of p-p70S6K; higher nuclear and cytoplasmic expression of p-4E-BP1 and of Notch-1; lower cytoplasmic expression of p85αPI3K, p-p70S6K and p-ERK1/2; and lower PTEN Histo-scores (H-scores). PTEN H-score was inversely correlated with recurrence probability. In univariate survival analysis, nuclear expression of p-4E-BP1 and absence of p-ERK1/2 expression portended adverse prognosis, whereas in multivariate survival analysis, p-ERK1/2 expression emerged as an independent favourable prognostic factor. Treatment of the human meningioma cell line HBL-52 with the PI3K inhibitor LY294002 resulted in reduction of p-AKT, p-p70S6K and p-ERK1/2 protein levels. The complex interactions established between components of the PI3K/AKT/mTOR pathway, or with components of the MAPK, JAK/STAT and Notch-1 pathways, appear to be essential for facilitating and fuelling meningioma progression.

Comparative immunohistochemical analysis of aurora-A and aurora-B expression in human glioblastomas. Associations with proliferative activity and clinicopathological features.

In the present study, we carried out a comparative immunohistochemical analysis of aurora-A and aurora-B expression in 40 patients with primary glioblastomas, and attempted to identify any associations with Ki-67 index and the patients' clinical features. The impact of various treatment modalities and proliferative activity on patient outcome was also assessed. Immunohistochemistry was carried out using formalin-fixed and paraffin-embedded tissue sections. Aurora-A expression was higher in tumors with high Ki-67 expression (p=0.01) and was positively, though marginally, related to aurora-B expression (p=0.085). Aurora-B expression was not linked to Ki-67 expression (p=0.182). Lower aurora-A immunohistochemical expression, chemotherapy administration, and tumor localization in one lobe of the brain implied a greater probability of patient survival in univariate analysis (p=0.044, p=0.008, p=0.041, respectively). Ki-67 and aurora-B immunoreactivities were not associated with patient survival (p=0.918 and p=0.539, respectively). To our knowledge, for the first time, the association between aurora-A and aurora-B expression, the correlation of aurora-A with Ki-67 index, and the prognostic impact of aurora-A expression were assessed in glioblastomas. Although we addressed a prognostic connotation of aurora-A, we presume that aurora-A and aurora-B play a complicated role within glioblastomas. Further examinations of larger series are required, so that definite conclusions can be drawn.

Simultaneous occurrence of cerebellar medulloblastoma and pituitary adenoma: A case report.

PURPOSE: We present the unusual occurrence of two distinct neoplasms in a 42-year-old woman with an operated pituitary adenoma 18 years ago. METHODS: Clinical history, magnetic resonance imaging studies and histopathological findings were utilized for our diagnostic considerations. RESULTS: Concomitant presence of a cerebellar medulloblastoma secondary disseminated within the spinal canal and a pituitary macroadenoma, was identified. CONCLUSION: To the best of our knowledge, this is the first reported case in which these two neoplasms are simultaneously occurred in the same individual. A short review of the literature is performed.