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ABSTRACT: Surgery for chronic subdural hematoma (CSDH) is performed to relieve brain displacement and high intracranial pressure (ICP). However, the intraoperative impression is often that the pressure inside the CSDH is low, despite marked clinical symptoms. We wanted to quantify the CSDH pressure and relate this to radiological and clinical characteristics. This prospective, population-based study of unilateral CSDHs was conducted over a 3-year period. CSDHs that were secondary to other conditions, re-operations, or CSDHs requiring other procedures than burr hole craniostomy under local anesthesia were excluded. Subdural pressure registration was performed via a simple manometric technique, and full compliance with a standardized protocol was mandatory. Sixty patients were included (mean age 76.2 years; for men, 77.4, and for women, 72.9). The mean pressure in the CSDHs was 15.2 cm H(2)O (range, 0-40) with no gender difference. Men had significantly larger volumes (mean 158.1 vs. 103.2 cm(3)) and midline shifts (mean 1.04 vs. 0.68 cm) than did women. Large hematomas with large midline shifts had higher pressures and more often required repeat surgery. With a patient's increasing age, the volumes and midline shifts seemed to become larger, whereas the pressures became lower. We did not find an association between repeat surgery and pressure or age. Our results are generally in line with those of previous studies reporting quantitative pressure registrations. However, there are important disparities regarding methodology, not least when comparing with various subjective scales that are widely used in clinical practice. A mean subdural pressure of 15.2 cm H(2)O is probably within the range of a normal ICP.
Journal of neurotrauma 06/2011; 29(1):137-42. · 4.25 Impact Factor
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ABSTRACT: This article provides a review of the transcriptomic expression profiling studies that have been performed on meningiomas so far. We discuss some future prospects and challenges ahead in the field of gene expression profiling.
We performed a systematic search in the PubMed and EMBASE databases in May 2010 using the following search terms alone or in combination: "meningioma", "microarray analysis", "oligonucleotide array sequence analysis", or "gene expression profiling". Only original research articles in English that had used RNA hybridized to high-resolution microarray chips to generate gene expression profiles were included.
We identified 13 articles matching the inclusion criteria. All studies had been performed during the last decade.
The main results of the studies can be grouped in three categories: (1) several groups have identified meningioma-specific genes and genes associated with the three WHO grades, and the main histological subtypes of grade I meningiomas; (2) one publication has shown that the general transcription profile of samples of all WHO grades differs in vivo and in vitro; (3) one report provides evidence that microarray technology can be used in an automated fashion to classify tumors. Due to lack of consensus on how microarray data are presented, possible general trends found across the studies are difficult to extract. This could obstruct the discovery of important genes and pathways universally involved in meningioma biology.
Acta Neurochirurgica 03/2011; 153(3):447-56. · 1.52 Impact Factor
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ABSTRACT: The vestibular nerve is the predilection site for schwannomas. Few transcriptomic studies have been performed on solely sporadic vestibular schwannomas (VSs).
To detect genes with altered expression levels in sporadic VSs.
We studied 25 VSs and 3 tibial nerves (controls) with the ABI 1700 microarray platform. Significance analysis of microarrays was performed to explore differential gene expression. Selected genes were validated with quantitative reverse transcriptase polymerase chain reaction. A tissue microarray was constructed for immunohistochemistry. Neurofibromatosis type II cDNA was sequenced for mutations.
The VSs formed 2 clusters based on the total expression of 23,055 genes. Tumor size, previous Gamma Knife surgery, neurofibromatosis type II mutations, and cystic tumors were distributed equally in both. Significance analysis of microarrays detected 1650 differentially expressed genes. On the top 500 list, several cancer-related genes with an unrecognized role in VSs were down-regulated: CAV1, TGFB3, VCAM1, GLI1, GLI2, PRKAR2B, EPHA4, and FZD1. Immunohistochemistry showed no CAV1 expression in the VSs. The ERK pathway was the central core in the network linking the differentially expressed genes. The previously reported VS candidate genes SPARC, PLAT, and FGF1 were up-regulated. Nineteen of 25 VSs had NF2 mutations.
Using microarray technology, we identified novel genes and pathways with a putative role in VSs, confirmed previous candidate genes, and found cancer-related genes with no reported role in VSs. Among these, down-regulation of CAV1 at both the mRNA and protein levels is of particular interest because this tumor suppressor normally is expressed in Schwann cells.
Neurosurgery 10/2010; 67(4):998-1019; discussion 1019. · 2.79 Impact Factor
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ABSTRACT: Arachnoid cysts (AC) are filled with liquid very similar to cerebrospinal fluid (CSF). The mechanisms of fluid accumulation have remained unknown; previous studies have however indicated both fluid secretion and a one-way valve as a mechanism. If the filling was caused by fluid secretion, mechanisms similar to those underlying CSF production would be anticipated. We have investigated the expression levels of all genes known to be involved in mammalian CSF production in surgically removed AC. Based on mRNA microarray analysis of AC and normal arachnoid tissue, we extracted the RNA expression profiles of all genes known to code for proteins involved in CSF production. A selection of genes was further investigated with quantitative real-time polymerase chain reaction (qRT-PCR). For selected CSF production proteins, electron microscopic immunogold techniques (EM) and Western blots were performed. Seven genes were expressed in both cysts and controls. The gene encoding the Na(+)-K(+)-2Cl(-) cotransporter NKCC1 was significantly up-regulated in AC. Gene expression data were supported by Western blot. EM demonstrated NKCC1 expressed at the plasma membranes of the cyst-lining cells. This result points at secretion as the main mechanism of cyst filling, and NKCC1 as the key candidate of fluid transport. Based on these findings, we hypothesize that selective NKCC1 inhibitors could be used in preventing expansion of temporal AC.
Experimental Neurology 08/2010; 224(2):424-8. · 4.70 Impact Factor
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ABSTRACT: Intracranial arachnoid cysts (AC) are membranous sacs filled with CSF-like fluid that are commonly found in the temporal fossa. The majority of ACs are congenital. Typical symptoms are headache, dizziness, and dyscognition. Little is known about genes that contribute to the formation of the cyst membranes.
In order to identify differences in gene expression between normal arachnoid membrane (AM) and cyst membrane, we have performed a high-resolution mRNA microarray analysis. In addition we have screened DNA from AC samples for chromosomal duplications or deletions using DNA microarray-based copy number variation analysis.
The transcriptome consisting of 33096 gene probes showed a near-complete similarity in expression between AC and AM samples. Only nine genes differed in expression between the two tissues: ASGR1, DPEP2, SOX9, SHROOM3, A2BP1, ATP10D, TRIML1, NMU were down regulated, whereas BEND5 was up regulated in the AC samples. Three of the AC samples had unreported human DNA copy number variations, all DNA gains.
Extending results of previous anatomical studies, the present study has identified a small subset of differentially expressed genes and DNA alterations in arachnoid cysts compared to normal arachnoid membrane.
Cerebrospinal Fluid Research 02/2010; 7:6. · 1.81 Impact Factor
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ABSTRACT: Working with patients with intracranial aneurysms, we have developed a clinical suspicion that there may be differences in the rupture rate of aneurysms depending on the aneurysm's anatomical location. The aim of the study was to examine the anatomical distribution of ruptured and unruptured intracranial aneurysms in a defined population.
We retrospectively included all patients with an aneurysm treated in our institution between 1 January 1990 and 31 December 1999, and collected the relevant data from the individual patient files. With the Koivisto categories for aneurysm location, we gathered the aneurysms into four categories: ACA, MCA, ICA, and VBA.
Four hundred forty-four aneurysms were included in the study: 361 in SAH patients and 83 in patients without SAH. ACA aneurysms were over-represented in the ruptured group (36.0% vs. 9.6%, p < 0.0001). MCA aneurysms were more frequent in the unruptured group (51.8% vs. 29.6%, p < 0.0002). Ruptured ACA aneurysms were over-represented among males (p < 0.0001), whereas ruptured ICA aneurysms were more frequent among females (p < 0.0001). Ruptured aneurysms in the posterior circulation were more frequently found on the left side (p < 0.0001).
This study shows that the anatomical distribution of aneurysms is different in SAH patients compared with patients with unruptured aneurysms. Haemodynamic features of the vessel of origin may explain the differences we have found. Furthermore, this study suggests that it is of particular importance to treat patients with incidentally found ACA aneurysms.
Acta Neurochirurgica 05/2009; 151(12):1569-74. · 1.52 Impact Factor
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ABSTRACT: Meningiomas of WHO grade I can usually be cured by surgical resection. However, some tumors may, despite their benign appearance, display invasive growth behavior. These tumors constitute a difficult clinical problem to handle. By histology alone, bone invasive meningiomas may be indistinguishable from their noninvasive counterparts. In this study we have examined the protein spectra in a series of meningiomas in search of protein expression patterns that may distinguish between bone invasive and noninvasive meningiomas. Tumor tissue from 13 patients with fibrous (6 invasive and 7 noninvasive) and 29 with meningothelial (10 invasive and 19 noninvasive) grade I meningiomas were analyzed by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI). Multivariate statistical methods were applied for data analyses. Comparing the protein spectra from invasive and noninvasive fibrous meningioma we found 22 peaks whose intensities were significantly different between the two groups (P < 0.001). Based on the expression pattern of these peaks we were able to perfectly separate the two entities (area under ROC curve = 1.0). In meningothelial meningioma the same comparison yielded six significantly differentially expressed peaks (P < 0.001), which to a large degree separated the invasive from noninvasive tissue (area under ROC curve = 0.873). By analyzing the protein spectra in benign meningiomas we could differentiate between invasive and noninvasive growth behavior in both fibrous and meningothelial meningiomas of grade I. A possibility for early identification of invasive grade I meningiomas may have a strong influence on the follow-up policy and the issue of early or late radiotherapy.
Journal of Neuro-Oncology 04/2009; 94(3):321-31. · 3.21 Impact Factor
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ABSTRACT: In order to investigate pathways that may influence on tumour development in meningiomas, we performed high throughput microarray analysis of the RNA expression and DNA copy number of 22 WHO grade I and five WHO grade II meningiomas. Since meningiomas derive from arachnoid cap cells, we used samples from four patients operated for arachnoid cysts as control tissue.
The expression of the tumour suppressor gene WW containing oxidoreductase (WWOX) was down-regulated, and the thymidylate synthase (TYMS) oncogene was up-regulated in all meningiomas as compared to arachnoid cysts. Unsupervised RNA cluster analysis showed that fibrous meningiomas gathered in two clusters, and thus were more homogeneous than the other meningiomas. The other histological subgroups could not be linked to any uniform gene expression signatures. Rearrangements were most abundant on chromosomes 1 and 22, but were identified on all except chromosome 16. The fibrous and mixed meningiomas generally had chromosomal deletions. Duplications were more frequent in the meningothelial meningiomas. WHO grade II meningiomas had increased chromosomal instability.
Decreased expression of the WWOX tumour suppressor gene and increased expression of the TYMS oncogene may be of importance for the development of human intracranial meningiomas. We have identified several genes (BMPR1B, DMD, RAMP1) with expression signatures specific for fibrous meningiomas. CGH analysis revealed distinct chromosomal patterns in relation to the histological subtypes of the meningiomas.
Journal of Neuro-Oncology 08/2008; 88(3):251-9. · 3.21 Impact Factor
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ABSTRACT: A right-handed woman of 90, taking aspirin 160 mg daily, suffered acute neck pain radiating to the shoulders, with right side hemiparesis and numbness occurring minutes thereafter. On admission 2.5 hrs later, examination showed paresis and hyporeflexia of the right limbs accompanied by neck stiffness and vertebral tenderness in level C7. Acute stroke was the initial working diagnosis. Cerebral CT was normal. Symptoms progressed with left arm numbness and left ancle clonus, and eight hours after symptom onset there was bilateral plantar inversion, reduced skin prick sensibility below C4, bladder paresis and anal sphincter hypotonia. CT myelography revealed an intraspinal mass extending from C2 to C6. 14 hours after symptom onset, a spinal epidural haematoma was removed by spinal laminectomy. Recovery and functional outcome was good. Symptoms, work-up and treatment are discussed with reference to previous publications.
Tidsskrift for den Norske laegeforening 09/2006; 126(15):1931-3.
