Expression of endoplasmic reticulum stress proteins is a candidate marker of brain metastasis in both ErbB-2+ and ErbB-2- primary breast tumors.

The increasing incidence of breast cancer brain metastasis in patients with otherwise well-controlled systemic cancer is a key challenge in cancer research. It is necessary to understand the properties of brain-tropic tumor cells to identify patients at risk for brain metastasis. Here we attempt to identify functional phenotypes that might enhance brain metastasis. To obtain an accurate classification of brain metastasis proteins, we mapped organ-specific brain metastasis gene expression signatures onto an experimental protein-protein interaction network based on brain metastatic cells. Thirty-seven proteins were differentially expressed between brain metastases and non-brain metastases. Analysis of metastatic tissues, the use of bioinformatic approaches, and the characterization of protein expression in tumors with or without metastasis identified candidate markers. A multivariate analysis based on stepwise logistic regression revealed GRP94, FN14, and inhibin as the best combination to discriminate between brain and non-brain metastases (ROC AUC = 0.85, 95% CI = 0.73 to 0.96 for the combination of the three proteins). These markers substantially improve the discrimination of brain metastasis compared with ErbB-2 alone (AUC = 0.76, 95% CI = 0.60 to 0.93). Furthermore, GRP94 was a better negative marker (LR = 0.16) than ErbB-2 (LR = 0.42). We conclude that, in breast carcinomas, certain proteins associated with the endoplasmic reticulum stress phenotype are candidate markers of brain metastasis.

In vivo proton magnetic resonance spectroscopy of intraventricular tumours of the brain.

The aim of this study was to assess the usefulness of proton MR spectroscopy in the diagnosis of intraventricular tumours. Fifty-two intraventricular tumours pertaining to 16 different tumour types were derived from our database. All cases had single-voxel proton MR spectroscopy performed at TE at both 30 and 136 ms at 1.5 T. The Mann-Whitney U test was used to search for the most discriminative datapoints each tumour type. Characteristic trends were found for some groups: high Glx and Ala in meningiomas (p < 0.001 and p < 0.01, respectively), high mobile lipids in metastasis (p < 0.001), high Cho in PNET (p < 0.001), high mI + Gly in ependymoma (p < 0.001), high NAC (p < 0.01) in the absence of the normal brain parenchyma pattern in colloid cysts, and high mI/Gly and Ala in central neurocytoma. Proton MR spectroscopy provides additional metabolic information that could be useful in the diagnosis of intraventricular brain tumors.

Identification of the sensorimotor cortex with functional MRI: frequency and actual contribution in a neurosurgical context.

BACKGROUND AND PURPOSE: We assessed the actual frequency of motor functional MRI (fMRI) in a neurosurgical environment and estimated the extent to which it aided surgeons' identifications of the sensorimotor cortex. METHODS: During five consecutive years, an fMRI protocol aimed at generating a selective activation of the hand cortical area was prescribed to 147 patients showing a centrally located space-occupying lesion, which represents 6.7% of all assisted surgical candidates showing an intracranial mass. Three senior neurosurgeons indicated the position of the sensorimotor cortex on two different anatomical displays, reporting confidence ratings for each decision. RESULTS: The sensorimotor cortex could not be identified in 16.5% of cases using conventional anatomical MRI, and in 15% of cases using 3-dimensional reconstructions. In an additional 12.5% of cases, the neurosurgeons were not confident when they correctly identified the sensorimotor cortex. The tumor distorting effect on central region anatomy significantly contributed to sensorimotor cortex misidentification. fMRI, by contrast, showed a selective activation indicating the position of the sensorimotor cortex in all but 4% of cases. CONCLUSIONS: In our neurosurgical environment, fMRI was prescribed to a selected group of surgical candidates showing a centrally located brain lesion. Compared to conventional anatomical imaging, fMRI does appear to improve the identification of sensorimotor cortex.

Contralateral hearing loss after vestibular schwannoma surgery: case report.

OBJECTIVE: To describe a case of contralateral hearing loss (CHL) in vestibular schwannoma (VS) surgery and to discuss the factors potentially related with this complication. CLINICAL PRESENTATION: A 48-year-old man awakened with complete bilateral hearing loss after an uneventful retrosigmoid excision of a 20 mm left-sided VS. The patient had no complaints of vertigo or facial palsy on the contralateral side. The hearing loss proved to be endocochlear in origin and no improvement was observed after a 24-month follow-up period. DISCUSSION: CHL in VS surgery is not commonly reported but can occur frequently as a subclinical phenomenon if it is specially addressed. The cause is a compensatory endolymphatic hydrops generated by the loss of cerebrospinal fluid. In this circumstance, the hearing loss is usually reversible within 3 months, but irreversible cases have been described. Vascular damage to the cochlea can be another explanation in irreversible cases. The significance of other potential factors described in the literature as a cause of CHL in VS surgery is less clear. CONCLUSION: A case of CHL after VS surgery is presented. The hearing loss proved to be endochlear in origin and irreversible in nature. Irreversible damage to the cochlea resulting from loss of cerebrospinal fluid or vascular injury is probably related in this case reported.

Brain tumor classification by proton MR spectroscopy: comparison of diagnostic accuracy at short and long TE.

BACKGROUND AND PURPOSE: Different TE can be used for obtaining MR spectra of brain tumors. The purpose of this study was to determine the influence of the TE used in brain tumor classification by comparing the performance of spectra obtained at two different TE (30 ms and 136 ms). METHODS: One hundred fifty-one studies of patients with brain tumors (37 meningiomas, 12 low grade astrocytomas, 16 anaplastic astrocytomas, 54 glioblastomas, and 32 metastases) were retrospectively selected from a series of 378 consecutive examinations of brain masses. Single voxel proton MR spectroscopy at TE 30 ms and 136 ms was performed with point-resolved spectroscopy in all cases. Fitted areas of nine resonances of interest were normalized to water. Tumors were classified into four groups (meningioma, low grade astrocytoma, anaplastic astrocytoma, and glioblastoma-metastases) by means of linear discriminant analysis. The performance of linear discriminant analysis at each TE was assessed by using the leave-one-out method. RESULTS: Tumor classification was slightly better at short TE (123 [81%] of 151 cases correctly classified) than at long TE (118 [78%] of 151 cases correctly classified). Meningioma was the only group that showed higher sensitivity and specificity at long TE. Improved results were obtained when both TE were considered simultaneously: the suggested diagnosis was correct in 105 (94%) of 112 cases when both TE agreed, whereas the correct diagnosis was suggested by at least one TE in 136 (90%) of 151 cases. CONCLUSION: Short TE provides slightly better tumor classification, and results improve when both TE are considered simultaneously. Meningioma was the only tumor group in which long TE performed better than short TE.

Prognostic implication of clinical, radiologic, and pathologic features in patients with anaplastic gliomas.

BACKGROUND: The clinical evolution of anaplastic glioma (anaplastic astrocytoma, oligodendroglioma, and oligoastrocytoma) is variable. Previous studies merged patients with anaplastic glioma and the much more common glioblastoma multiforme. Therefore, the conclusions on prognostic factors reflected in part the consequences of an analysis in a heterogeneous population. METHODS: To identify clinical, neuroradiologic, pathologic, and molecular factors with prognostic significance, we analyzed 95 treated patients with a histologic diagnosis of anaplastic glioma. Variables included age, gender, clinical manifestations at diagnosis (seizures, focal neurologic deficit, and cognitive changes), computed tomographic (CT) scan characteristics (diffuse, ring, and no enhancement), tumor location, extent of resection, histopathology, postoperative Karnofsky performance status (KPS) score, adjuvant chemotherapy, tumor response, proliferation index (Ki-67 expression), and p53, p16, pRb, and epidermal growth factor receptor immunohistochemical expression. RESULTS: Ninety-five patients with a histologic diagnosis of anaplastic astrocytoma (73%), anaplastic oligoastrocytoma (16.6%), or anaplastic oligodendroglioma (10.4%) constituted the basis of this study. Median overall survival was 29 months. Multivariate analysis revealed that an age of 49 years or younger (P < 0.03), postoperative KPS score of 80 or higher (P < 0.007), absence of ring enhancement (P = 0.03), and a proliferation index of 5.1% or lower (P = 0.044) were independently associated with longer survival. The presence of an oligodendroglial component was associated with better prognosis in the univariate analysis (P = 0.009), although this lost power in the multivariate analysis. CONCLUSIONS: In addition to previously recognized prognostic variables such as age and KPS score, CT ring enhancement and tumor proliferation index were identified as independent predictors of survival in a homogeneous series of patients with anaplastic gliomas.

Proton magnetic resonance spectroscopy ((1)H MRS) of human brain tumours: assessment of differences between tumour types and its applicability in brain tumour categorization.

Our objective was to evaluate the usefulness of proton magnetic resonance spectroscopy ((1)H MRS) in categorizing brain tumours. In vivo single-voxel (1)H MRS at an echo time of 136 ms was performed in 108 patients with brain neoplasms that included 29 meningiomas (MEN), 15 low-grade astrocytomas (LGA), 12 anaplastic astrocytomas (AA), 25 glioblastomas (GBM) and 27 metastases (MET). Time-domain fitted areas of nine resonances were evaluated in all spectra. Twenty-five additional tumours were prospectively included as independent test set. Differences in at least two resonances were found in all pairwise comparisons of tumour groups except in GBM vs MET. Large lipid resonance at 1.30 ppm was found to be characteristic of GBM and MET, and alanine was characteristic of MEN. Significant differences were found between LGA and AA in choline-containing compounds and total creatine resonances. When implemented in a stepwise algorithm, these findings correctly classified 84% (21 of 25) tumours in the independent test set. Some additional utility was found in glycine/myo-inositol at 3.55 ppm for bilateral differentiation between GBM and MET (9 of 11, 82% correct classification in the test set). (1)H MRS provides useful information to categorize the most common brain tumours that can be implemented in clinical practice with satisfactory results.

Adult primitive neuroectodermal tumor: proton MR spectroscopic findings with possible application for differential diagnosis.

PURPOSE: To assess the utility of proton magnetic resonance (MR) spectroscopy in the clinical categorization of primitive neuroectodermal tumors (PNETs) in adults. MATERIALS AND METHODS: In vivo proton MR spectroscopy was performed with an echo time of 136 msec in nine adults with PNET, and findings were retrospectively compared with spectroscopic findings of 22 meningiomas, 12 low-grade astrocytomas, eight anaplastic astrocytomas, 23 glioblastomas, and 21 metastases. Nine resonances were semiquantitatively evaluated. Statistical analysis was performed by using Kruskal-Wallis and Mann-Whitney U tests. The Hochberg correction was applied for multiple comparisons. Results were prospectively validated in 24 tumors of the six types included in the study. RESULTS: The resonances of choice for identifying PNET were alanine (P <.001) and glutamate and glutamine (P =.004), both decreased with respect to meningioma; choline increased with respect to low-grade (P <.001) and anaplastic astrocytoma (P =.055); and lipids at 1.30 ppm decreased and choline and other trimethyl-amine-containing compounds increased with respect to glioblastoma (P <.001 and P =.004, respectively) and metastasis (P <.001 and P =.021, respectively). We developed an algorithm for bilateral differential diagnosis between PNET and other tumor types. The leave-one-out method was used to test the five possible differential situations in the retrospective data set, with the following results: PNET versus meningioma, 31/23/5/3 (number of total/correct/unclassifiable/incorrect procedures); PNET versus low-grade astrocytoma, 21/19/2/0; PNET versus anaplastic astrocytoma, 17/6/9/2; PNET versus glioblastoma, 32/28/2/2; and PNET versus metastasis, 30/27/1/2. In total, 131 consecutive procedures produced 103 (79%) correct classifications and nine (7%) misclassifications. Twenty-five (78%) of 32 possible procedures in the prospective independent test set produced correct classifications and four (13%) produced incorrect classifications. CONCLUSION: In vivo proton MR spectroscopy provides useful information in clinical differentiation between PNETs and common brain tumors in adults.