A history of prior subarachnoid hemorrhage is often absent in patients with superficial siderosis (SS). A past history of trauma is common. Prior intradural surgery may be an additional risk factor. Xanthochromia or the presence of red blood cells in the CSF is a common finding. Only rarely does angiography demonstrate the bleeding source. The presence of a fluid-filled collection in the spinal canal is a common finding on MRI and is likely related to the SS. With longitudinally extensive cavities, a dynamic CT myelogram may help localize the defect and direct the site of laminectomy. Surgical repair of a dural defect, if present, should be considered. Surgical correction of bleeding should be documented by CSF examination months after surgery. Friable vessels in the dural defect are a possible source of the chronic bleeding.

Object Various studies report outcomes of vestibular schwannoma (VS) surgery, but few studies have compared outcomes across the various approaches. The authors conducted a systematic review of the available data on VS surgery, comparing the different approaches and their associated complications. Methods MEDLINE searches were conducted to collect studies that reported information on patients undergoing VS surgery. The authors set inclusion criteria for such studies, including the availability of follow-up data for at least 3 months, inclusion of preoperative and postoperative audiometric data, intraoperative monitoring, and reporting of results using established and standardized metrics. Data were collected on hearing loss, facial nerve dysfunction, persistent postoperative headache, CSF leak, operative mortality, residual tumor, tumor recurrence, cranial nerve (CN) dysfunction involving nerves other than CN VII or VIII, and other neurological complications. The authors reviewed data from 35 studies pertaining to 5064 patients who had undergone VS surgery. Results The analyses for hearing loss and facial nerve dysfunction were stratified into the following tumor categories: intracanalicular (IC), size (extrameatal diameter) < 1.5 cm, size 1.5–3.0 cm, and size > 3.0 cm. The middle cranial fossa approach was found to be superior to the retrosigmoid approach for hearing preservation in patients with tumors < 1.5 cm (hearing loss in 43.6% vs 64.3%, p < 0.001). All other size categories showed no significant difference between middle cranial fossa and retrosigmoid approaches with respect to hearing loss. The retrosigmoid approach was associated with significantly less facial nerve dysfunction in patients with IC tumors than the middle cranial fossa method was; however, neither differed significantly from the translabyrinthine corridor (4%, 16.7%, 0%, respectively, p < 0.001). The middle cranial fossa approach differed significantly from the translabyrinthine approach for patients with tumors < 1.5 cm, whereas neither differed from the retrosigmoid approach (3.3%, 11.5%, and 7.2%, respectively, p = 0.001). The retrosigmoid approach involved less facial nerve dysfunction than the middle cranial fossa or translabyrinthine approaches for tumors 1.5–3.0 cm (6.1%, 17.3%, and 15.8%, respectively; p < 0.001). The retrosigmoid approach was also superior to the translabyrinthine approach for tumors > 3.0 cm (30.2% vs 42.5%, respectively, p < 0.001). Postoperative headache was significantly more likely after the retrosigmoid approach than after the translabyrinthine approach, but neither differed significantly from the middle cranial fossa approach (17.3%, 0%, and 8%, respectively; p < 0.001). The incidence of CSF leak was significantly greater after the retrosigmoid approach than after either the middle cranial fossa or translabyrinthine approaches (10.3%, 5.3%, 7.1%; p = 0.001). The incidences of residual tumor, mortality, major non-CN complications, residual tumor, tumor recurrence, and dysfunction of other cranial nerves were not significantly different across the approaches. Conclusions The middle cranial fossa approach seems safest for hearing preservation in patients with smaller tumors. Based on the data, the retrosigmoid approach seems to be the most versatile corridor for facial nerve preservation for most tumor sizes, but it is associated with a higher risk of postoperative pain and CSF fistula. The translabyrinthine approach is associated with complete hearing loss but may be useful for patients with large tumors and poor preoperative hearing.

The response to epilepsy surgery during the 1st follow-up year is a reliable indicator of the long-term Engel Class I postoperative outcome. This finding may have important implications for patient counseling and postoperative discontinuation of anticonvulsant medications.

Cancer stem cells (CSCs) or cancer initiating cells (CICs) maintain self-renewal and multilineage differentiation properties of various tumors, as well as the cellular heterogeneity consisting of several subpopulations within tumors. CSCs display the malignant phenotype, self-renewal ability, altered genomic stability, specific epigenetic signature, and most of the time can be phenotyped by cell surface markers (e.g., CD133, CD24, and CD44). Numerous studies support the concept that non-stem cancer cells (non-CSCs) are sensitive to cancer therapy while CSCs are relatively resistant to treatment. In glioblastoma stem cells (GSCs), there is clonal heterogeneity at the genetic level with distinct tumorigenic potential, and defined GSC marker expression resulting from clonal evolution which is likely to influence disease progression and response to treatment. Another level of complexity in glioblastoma multiforme (GBM) tumors is the dynamic equilibrium between GSCs and differentiated non-GSCs, and the potential for non-GSCs to revert (dedifferentiate) to GSCs due to epigenetic alteration which confers phenotypic plasticity to the tumor cell population. Moreover, exposure of the differentiated GBM cells to therapeutic doses of temozolomide (TMZ) or ionizing radiation (IR) increases the GSC pool both in vitro and in vivo. This review describes various subtypes of GBM, discusses the evolution of CSC models and epigenetic plasticity, as well as interconversion between GSCs and differentiated non-GSCs, and offers strategies to potentially eliminate GSCs.

Examination of tissue sections using desorption electrospray ionization (DESI)-MS revealed phospholipid-derived signals that differ between gray matter, white matter, gliomas, meningiomas, and pituitary tumors, allowing their ready discrimination by multivariate statistics. A set of lower mass signals, some corresponding to oncometabolites, including 2-hydroxyglutaric acid and N-acetylaspartic acid, was also observed in the DESI mass spectra, and these data further assisted in discrimination between brain parenchyma and gliomas. The combined information from the lipid and metabolite MS profiles recorded by DESI-MS and explored using multivariate statistics allowed successful differentiation of gray matter (n = 223), white matter (n = 66), gliomas (n = 158), meningiomas (n = 111), and pituitary tumors (n = 154) from 58 patients. A linear discriminant model used to distinguish brain parenchyma and gliomas yielded an overall sensitivity of 97.4% and a specificity of 98.5%. Furthermore, a discriminant model was created for tumor types (i.e., glioma, meningioma, and pituitary), which were discriminated with an overall sensitivity of 99.4% and a specificity of 99.7%. Unsupervised multivariate statistics were used to explore the chemical differences between anatomical regions of brain parenchyma and secondary infiltration. Infiltration of gliomas into normal tissue can be detected by DESI-MS. One hurdle to implementation of DESI-MS intraoperatively is the need for tissue freezing and sectioning, which we address by analyzing smeared biopsy tissue. Tissue smears are shown to give the same chemical information as tissue sections, eliminating the need for sectioning before MS analysis. These results lay the foundation for implementation of intraoperative DESI-MS evaluation of tissue smears for rapid diagnosis. ambient ionization | MS imaging | multivariate statistics | pathology | neurosurgery M S is increasingly being used in medicine (e.g., in clinical chemistry, pharmaceutical development, and proteomics). Ambient ionization methods generate ions under atmospheric conditions, with minimal to no sample preparation (1). Desorption electrospray ionization (DESI), an ambient method that uses a spray of charged solvent as the projectile, provides rapid chemical information while preserving tissue and cellular morphology, allowing subsequent histopathology on the same specimen (2). This feature allows integration of DESI-MS into current workflows and postacquisition pathology. DESI-MS has been used to study prostate cancer (3), bladder cancer (4), kidney cancer (5), seminoma (6), lymphoma (7), gastrointestinal cancer (8), and others. In each case, the recorded pattern of lipid signals allows the differentiation of cancer from normal tissue. DESI-MS has been previously used to explore chemical differences among glioma subtypes, grades, and tumor cell concentrations (relative percentage of tumor compared with parenchyma) (9, 10). Meningiomas have also been studied previously and were distinguished from normal dura mater (11).T...

Focal cortical dysplasias are a distinct subgroup of malformations of cortical development and have a favorable outcome after resection. The epileptogenic zone often extends beyond the abnormality found on neuroimaging. Resection of the epileptogenic zone guided by histopathologically proven clear margins is associated with an improved seizure outcome.

Intraoperative desorption electrospray ionization-mass spectrometry (DESI-MS) is used to characterize tissue smears by comparison with a library of DESI mass spectra of pathologically determined tissue types. Measurements are performed in the operating room within 3 min. These mass spectra provide direct information on tumor infiltration into white or gray brain matter based on N-acetylaspartate (NAA) and on membrane-derived complex lipids. The mass spectra also indicate the isocitrate dehydrogenase mutation status of the tumor via detection of 2-hydroxyglutarate, currently assessed postoperatively on biopsied tissue using immunohistochemistry. Intraoperative DESI-MS measurements made at surgeon-defined positions enable assessment of relevant disease state of tissue within the tumor mass and examination of the resection cavity walls for residual tumor. Results for 73 biopsies from 10 surgical resection cases show that DESI-MS allows detection of glioma and estimation of high tumor cell percentage (TCP) at surgical margins with 93% sensitivity and 83% specificity. TCP measurements from NAA are corroborated by indirect measurements based on lipid profiles. Notably, high percentages (>50%) of unresected tumor were found in one-half of the margin biopsy smears, even in cases where postoperative MRI suggested gross total tumor resection. Unresected tumor causes recurrence and malignant progression, as observed within a year in one case examined in this study. These results corroborate the utility of DESI-MS in assessing surgical margins for maximal safe tumor resection. Intraoperative DESI-MS analysis of tissue smears, ex vivo, can be inserted into the current surgical workflow with no alterations. The data underscore the complexity of glioma infiltration.e describe the rapid analysis of neurological tissue smears by desorption electrospray ionization-mass spectrometry (DESI-MS) in the operating room (OR) from 10 subjects who underwent glioma resection. Biopsied tissue specimens from surgeon-defined positions in the tumor and the walls of the resection cavity were smeared onto glass microscope slides and sprayed with charged solvent droplets to extract molecules from the unprocessed tissue while the splashed secondary droplets were vacuumed into a customized ion-trap mass spectrometer modified for use in the OR at Indianapolis IU (Indiana University) Health Methodist Hospital. Three separate items of information were sought from the DESI mass spectra: (i) tissue type, specifically whether glioma, white brain matter, gray brain matter, or mixtures of these types; (ii) isocitrate dehydrogenase (IDH) status, i.e., whether or not this enzyme carries a characteristic mutation, the presence of which is associated with more favorable prognosis; and (iii) the tumor cell percentage (TCP) in the sampled biopsy as a measure of tumor infiltration (the latter is arguably the most actionable intraoperatively and the one for which the least information is currently available).The infiltrative nature of most gliomas, as well as visu...

abbreviatioNs BBB = blood-brain barrier; GTR = gross-total resection; IQR = interquartile range; NHA = normal human astrocyte; PBS = phosphate-buffered saline; PDGF = platelet-derived growth factor; PDGFB = PDGF beta; PDGFR = PDGF receptor; PDGFRA = PDGFR alpha; RCAS = replication-competent avian sarcoma-leukosis; RFP = red fluorescent protein; tva = tumor virus A. 6 Department of Pathology and Laboratory Medicine, Indiana University; and 7 Goodman Campbell Brain and Spine, Department of Neurological Surgery, Indiana University, Indianapolis, Indiana obJect Intravenous fluorescein sodium has been used during resection of high-grade gliomas to help the surgeon visualize tumor margins. Several studies have reported improved rates of gross-total resection (GTR) using high doses of fluorescein sodium under white light. The recent introduction of a fluorescein-specific camera that allows for high-quality intraoperative imaging and use of very low dose fluorescein has drawn new attention to this fluorophore. However, the ability of fluorescein to specifically stain glioma cells is not yet well understood. methods The authors designed an in vitro model to assess fluorescein uptake in normal human astrocytes and U251 malignant glioma cells. An in vivo experiment was also subsequently designed to study fluorescein uptake by intracranial U87 malignant glioma xenografts in male nonobese diabetic/severe combined immunodeficient mice. A genetically induced mouse glioma model was used to adjust for the possible confounding effect of an inflammatory response in the xenograft model. To assess the intraoperative application of this technology, the authors prospectively enrolled 12 patients who underwent fluorescein-guided resection of their high-grade gliomas using low-dose intravenous fluorescein and a microscope-integrated fluorescence module. Intraoperative fluorescent and nonfluorescent specimens at the tumor margins were randomly analyzed for histopathological correlation. results The in vitro and in vivo models suggest that fluorescein demarcation of glioma-invaded brain is the result of distribution of fluorescein into the extracellular space, most likely as a result of an abnormal blood-brain barrier. Glioblastoma tumor cell-specific uptake of fluorescein was not observed, and tumor cells appeared to mostly exclude fluorescein. For the 12 patients who underwent resection of their high-grade gliomas, the histopathological analysis of the resected specimens at the tumor margin confirmed the intraoperative fluorescent findings. Fluorescein fluorescence was highly specific (up to 90.9%) while its sensitivity was 82.2%. False negatives occurred due to lack of fluorescence in areas of diffuse, low-density cellular infiltration. Margins of contrast enhancement based on intraoperative MRI-guided StealthStation neuronavigation correlated well with fluorescent tumor margins. GTR of the contrast-enhancing area as guided by the fluorescent signal was achieved in 100% of cases based on postoperative MRI. coNclusioNs Fluorescein sodiu...