Biomedical subjects

J C Tonn

Publications and source records attributed to J C Tonn.

At least 37 records · Page 2Linked to original sources

PubMed2002

Sequential MRI and MR spectroscopy in embolized meningiomas: correlation with surgical and histopathological findings.

The preoperative embolization of meningiomas is commonly used to facilitate surgery. The purpose of this study was to evaluate the morphological and metabolic changes in embolized meningiomas and to correlate the results with surgical and histopathological findings. In a prospective study, 36 patients with intracranial meningiomas were included. The extent of devascularization was assessed by angiography and MR volumetry. MRI and MR spectroscopy (MRS) were performed before and sequentially after embolization. At surgery, blood loss was measured and intraoperative duplex-mode ultrasound was applied to identify avascular tumor portions. Histopathological specimens were evaluated for the histological subtype, localization and extent of necrotic tumor portions. Postembolization MRI revealed a variable pattern of secondary revascularization and devascularization with an early onset following embolization. In all patients, peripheral secondary enhancement was present which histopathologically represented a thin layer of vital tumor tissue. MRS revealed lactate in devascularized areas immediately after embolization. Lipids were not observed before the 3rd day after embolization and were always associated with avascular and soft tissue at the time of surgery. Embolized meningiomas feature a variable dynamic with the potential for revascularization and secondary devascularization. Lipid signals indicate avascular and soft tissue at surgery. In case of delayed surgery, MRI and MRS should be performed in order to exclude revascularization and to establish the fatty degeneration of the meningioma.

Embolization, Therapeutic↗

PubMed2002

Human medulloblastomas lack point mutations and homozygous deletions of the hSNF5/INI1 tumour suppressor gene.

Medulloblastomas (MBs) are malignant primitive neuroectodermal tumours (PNETs) of the cerebellum occurring predominantly in childhood. The association of monosomy of chromosome 22 with MB is controversial. Atypical teratoid/rhabdoid tumours (AT/RTs) of the brain share clinical and histological features with MBs and supratentorial PNETs (sPNETs). In particular, AT/RTs can be misdiagnosed as MBs and sPNETs because AT/RTs frequently contain areas of primitive neuroepithelial cells similar to PNETs. Recently, mutations of the tumour suppressor gene hSNF5/INI1, located on 22q11.23, have been described in AT/RTs, MBs and sPNETs, with conflicting data on the prevalence of hSNF5/INI1 mutations in the latter entities. Therefore, we screened MBs for point mutations and homozygous deletions of the hSNF5/INI1 tumour suppressor gene. In 90 MBs, no mutations of the hSNF5/INI1 gene were identified. Thus, our study virtually rules out hSNF5/INI1 as a tumour suppressor gene involved in the pathogenesis of medulloblastoma.

Adolescent↗

PubMed2002

Molecular genetic analysis of the TP53, PTEN, CDKN2A, EGFR, CDK4 and MDM2 tumour-associated genes in supratentorial primitive neuroectodermal tumours and glioblastomas of childhood.

Supratentorial primitive neuroectodermal tumours (sPNETs) are malignant central nervous system tumours of childhood which are histologically characterized by poorly differentiated neuroepithelial cells with the capacity for divergent differentiation into glial, neuronal, myogenic or melanotic lines. The histological differential diagnosis between sPNET and glioblastoma multiforme (GBM) may be difficult, particularly as GBMs can sometimes demonstrate a poorly differentiated PNET-like phenotype. To identify molecular genetic markers that may distinguish sPNET and GBM, we investigated 12 cerebral sPNETs and six GBMs from paediatric patients for genetic alterations of the TP53, PTEN, CDKN2A, EGFR, CDK4 and MDM2 genes, as well as for allelic loss on chromosome arms 10q and 17p. Mutations of the TP53 tumour suppressor gene were found in one of 12 sPNETs (8%) and two of six GBMs (33%). None of the sPNETs but two of six GBMs (33%, including one GBM with a TP53 mutation) showed allelic losses on chromosome arm 17p. PTEN mutations were detected in one of 12 sPNET (8%) and one of six GBMs (17%). None of the sPNETs and GBMs carried a homozygous deletion involving the CDKN2A tumour suppressor gene. No amplification of the EGFR, CDK4 or MDM2 proto-oncogenes was detected. Taken together, our results indicate that paediatric GBMs differ from sPNETs by a higher incidence of allelic losses on 17p and TP53 mutations. In addition, the patterns of genetic alterations in sPNETs and paediatric GBMs appear to be distinct from those in cerebellar medulloblastomas and adult GBMs, respectively.

Adolescent↗

PubMed2001

Deletions of AXIN1, a component of the WNT/wingless pathway, in sporadic medulloblastomas.

Medulloblastoma (MB) represents the most frequent malignant brain tumor in children. Most MBs appear sporadically; however, their incidence is highly elevated in two inherited tumor predisposition syndromes, Gorlin's and Turcot's syndrome. The genetic defects responsible for these diseases have been identified. Whereas Gorlin's syndrome patients carry germ-line mutations in the patched (PTCH) gene, Turcot's syndrome patients with MBs carry germ-line mutations of the adenomatous polyposis coli (APC) gene. The APC gene product is a component of a multiprotein complex controlling beta-catenin degradation. In this complex, Axin plays a major role as scaffold protein. Whereas APC mutations are rare in sporadic MBs, a hot-spot region of beta-catenin (CTNNB1) mutations was identified in a subset of MBs. To find out if Axin is also involved in the pathogenesis of sporadic MBs, we analyzed 86 MBs and 11 MB cell lines for mutations in the AXIN1 gene. Using single-strand conformation polymorphism analysis, screening for large deletions by reverse transcription-PCR, and sequencing analysis, a single somatic point mutation in exon 1 (Pro255Ser) and seven large deletions (12%) of AXIN1 were detected. This indicates that AXIN1 may function as a tumor suppressor gene in MBs.

Adolescent↗

PubMed2001

Somatic mutations of WNT/wingless signaling pathway components in primitive neuroectodermal tumors.

Primitive neuroectodermal tumors (PNETs) represent the most frequent malignant brain tumors in childhood. The majority of these neoplasms occur in the cerebellum and are classified as medulloblastomas (MB). Most PNETs develop sporadically; however, their incidence is highly elevated in patients carrying germline APC gene mutations. The APC gene encodes a central component of the WNT/wingless developmental signaling pathway. It regulates the levels of cytoplasmic beta-catenin protein that plays a central role in neural development and cell proliferation. We analyzed 87 sporadic PNETs and 10 PNET cell lines for mutations of the APC gene and beta-catenin (CTNNB1) gene using single strand conformational polymorphism (SSCP) and sequencing analysis. We examined the mutation cluster region of APC (codons 1255--1641) for germline variants and somatic mutations. The medulloblastoma cell line MHH-MED-2 carried a Glu1317Gln missense germline variant and a sporadic MB sample showed a somatic Pro1319Leu substitution. Mutational analysis of exon 3 of CTNNB1 uncovered 4 PNETs (4.8%) with somatic missense mutations. These mutations caused amino acid substitutions in 3 of 80 medulloblastomas (Ser33Phe, Ser33Cys and Ser37Cys) and 1 of 4 supratentorial PNETs (Gly34Val). All mutations affected GSK-3 beta phosphorylation sites of the degradation targeting box of beta-catenin and resulted in nuclear beta-catenin protein accumulation. Deletions of CTNNB1 were not detected by PCR amplification with primers spanning exons 1--5. Our data indicate that inappropriate activation of the WNT/wingless signaling pathway by mutations of its components may contribute to the pathogenesis of a subset of PNETs.

Adenomatous Polyposis Coli Protein↗

PubMed2001

Diagnosing dural metastases: the value of 1H magnetic resonance spectroscopy.

The purpose of this study was to assess the value of MRI, MR spectroscopy (MRS) and intra-arterial angiography in the preoperative diagnosis of extra-axial dural-based masses. We prospectively studied 54 patients who underwent preoperative MRI, MRS and angiography. Histologically there were 50 meningiomas and four dural metastases. MRI and angiography did not allow reliable differentiation between meningiomas and metastases. MRS showed elevated choline/creatine ratios in both meningiomas and metastases, but there were prominent lipid signals in all metastases and a lactate peak in two. This spectroscopic pattern was not found in meningiomas. However, following embolisation, they showed similar spectra, due to ischaemia and necrosis. We therefore believe MRS to be valuable in differential diagnosis of dural metastases and meningiomas prior to embolisation.

Aged↗

PubMed2001

Indications for a tumor suppressor gene at 22q11 involved in the pathogenesis of ependymal tumors and distinct from hSNF5/INI1.

Ependymomas account for approximately 9% of all neuroepithelial tumors and represent the most frequent neuroepithelial tumors of the spinal cord. In adults, allelic loss of chromosome arm 22q occurs in up to 60% of the cases studied. Some of these tumors show an altered neurofibromatosis type 2 (NF2) gene; in others, NF2 appears to be unaffected, indicating the involvement of another tumor suppressor gene. Recently, the tumor suppressor gene hSNF5/INI1, located on 22q11.23, has been shown to contribute to the pathogenesis of renal and extrarenal rhabdoid tumors. In addition, this gene may be responsible for a new hereditary syndrome predisposing to a variety of tumors designated "rhabdoid predisposition syndrome." In the present study, we analyzed a series of 53 ependymal tumors of 48 patients [4 myxopapillary ependymomas (WHO grade I), 3 subependymomas (WHO grade I), 18 ependymomas (WHO grade II), 21 anaplastic ependymomas (WHO grade III) and 2 ependymoblastomas (WHO grade IV)] for mutations and homozygous deletions in the coding region of the hSNF5/INI1 gene and for allelic loss of its flanking chromosomal regions in 39 ependymal tumors of 35 patients. Allelic loss was detected in 11 of 35 informative primary ependymal tumors (31%) with a common region of overlap covered by the markers D22S257 and D22S310 on 22q11 including the marker D22S301. However, a detailed molecular analysis of 53 ependymal tumors for mutations and homozygous deletion of the hSNF5/INI1 gene revealed no alterations. We conclude that the hSNF5/INI1 gene is not involved in the pathogenesis of human ependymal tumors with allelic loss on chromosome arm 22q and an intact NF2 locus. In addition, our study localizes a putative ependymoma tumor suppressor gene(s) to a domain of chromosome arm 22q flanked by the microsatellite markers D22S257 and D22S310.

Adolescent↗

PubMed2001

Analysis of the TSC2 gene in human medulloblastoma.

Medulloblastoma (MB) represents the most frequent malignant brain tumor of childhood. Recent studies have shown that deregulation of developmental control genes may play an important role in its pathogenesis. Tuberous sclerosis is associated with hamartomas and cortical tubers, consisting of both glial and neuronal cellular components. MBs can also show markers of these lineages, raising the question of the potential involvement of TSC genes in these malignant tumors. Here we investigated tuberous sclerosis 2 (TSC2), one of the two genes responsible for tuberous sclerosis, in sporadic MBs. We analyzed MBs for allelic losses at the TSC2 locus and for the frequency of a polymorphism first described in gangliogliomas. Sixty-eight MBs were examined for this polymorphism located in intron 4, 3 base pairs 5' to the first coding nucleotide of exon 5. The distribution of the alleles was significantly different in MBs as compared to 208 control samples, (P=0.0017, Chi-square test). In MBs the frequency of the rare allele (A2) was 0.184 (18.4%), whereas in the control group it occurred in a frequency of 8.7%. Microsatellite analysis of the TSC2 region in 50 tumors did not identify allelic losses. TSC2 mRNA transcript was detectable via reverse transcription-PCR in all tumors as well as in normal cerebellum. Northern blot analysis of an MB cell line homozygous for the rare allele of the polymorphism and two other cell lines homozygous for the frequent allele revealed normal splicing patterns and normal expression levels of the TSC2 transcript. These findings may indicate that the presence of the rare TSC2 allele is associated with a predisposition for the development of MBs.

Blotting, Northern↗

PubMed2001

Medulloblastoma displays distinct regional matrix metalloprotease expression.

Matrix metalloproteases (MMPs) play an important role in tissue remodeling and neoangiogenesis during tumor progression. Little is known about the presence and regional distribution of MMPs in medulloblastomas. Based on immunohistochemical, immunocytochemical and zymographical analysis is the present study illustrates the differential pattern of MMP expression for the medulloblastoma compared to that of glioma and ependymoma. In 10 examined medulloblastoma tumors gelatinase-A was strongly expressed by clusters of tumor cells. Gelatinase-B was, similar to glioma and ependymoma, predominantly found around endothelial cells. The DAB signal for macrophage metalloelastase was seen around macrophages and matrilysin was expressed by single tumor cells. Stromelysin-1 protein was detected in medulloblastoma but not in glioma or ependymoma. From the presented data it follows that each tumor entity might display its own characteristic MMP expression pattern.

Astrocytoma↗

PubMed2001

Extraneural metastases of primary brain tumors.

Extraneural metastasis (ENM) of primary brain tumors is arare occurence. Based on acritical analysis of the literature the present review focuses on illustrating special common features of these tumors with regard to immunological, cytokinetical and tumorbiological issues. In this respect much can be learned from the specific conditions following organ transplantation which is extensively discussed.

Adult↗

PubMed2001

Production of MMPs in human cerebral endothelial cells and their role in shedding adhesion molecules.

Matrix metalloproteinases (MMPs) are Zn2+-endopeptidases that seem to play an important role in chronic inflammatory diseases of the central nervous system by disrupting the blood-brain barrier (BBB) and mediating the destruction of myelin components. We therefore investigated the influence of the pro-inflammatory cytokine TNF-alpha. on the expression and activation of several MMPs in human cerebral endothelial cells (HCEC). HCEC constitutively express MMP-2 and MMP-3 mRNA, but only MMP-3 is upregulated on mRNA and protein level after TNF-alpha stimulation. MMP-9 and MMP-12 mRNA could only be detected under inflammatory conditions. Furthermore, MMPs are involved in shedding of cell surface molecules. We therefore investigated the influence of MMPs on the release of soluble adhesion molecules using marimastat, a specific broad-spectrum MMP inhibitor and other protease inhibitors like aprotinin or leupeptin. Only marimastat inhibited the TNF-alpha mediated release of sVCAM-1 in the supernatants of HCEC. Western blot results of culture supernatants supported the time dependent release of the complete extracellular portion of the VCAM-1 molecule. These data suggest that MMPs produced by HCEC are actively involved in the shedding of soluble adhesion molecules at the BBB.

Alternative Splicing↗

PubMed2000

Targeting angiogenesis inhibits tumor infiltration and expression of the pro-invasive protein SPARC.

The solid growth of high-grade glioma appears to be critically dependent on tumor angiogenesis. It remains unknown, however, whether the diffuse infiltration of glioma cells into healthy adjacent tissue is also dependent on the formation of new tumor vessels. Here, we analyze the relationship between tumor angiogenesis and tumor cell infiltration in an experimental glioma model. C6 cells were implanted into the dorsal skinfold chamber of nude mice, and tumor angiogenesis was monitored by intravital fluorescence videomicroscopy. Glioma infiltration was assessed by the extent of tumor cell invasion into the adjacent chamber tissue and by expression of SPARC, a cellular marker of glioma invasiveness. To test the hypothesis that glioma angiogenesis and glioma infiltration are codependent, we assessed tumor infiltration in both the presence and the absence of the angiogenesis inhibitor SU5416. SU5416 is a selective inhibitor of the VEGF/Flk-1 signal-transduction pathway, a critical pathway implicated in angiogenesis. Control tumors demonstrated both high angiogenic activity and tumor cell invasion accompanied by strong expression of SPARC in invading tumor cells at the tumor-host tissue border. SU5416-treated tumors demonstrated reduced vascular density and vascular surface in the tumor periphery accompanied by marked inhibition of glioma invasion and decreased SPARC expression. A direct effect of SU5416 on glioma cell motility and invasiveness was excluded by in vitro migration and invasion assays. These results suggest a crucial role for glioma-induced angiogenesis as a prerequisite for diffuse tumor invasion and a possible therapeutic role for anti-angiogenic compounds as inhibitors of both solid and diffuse infiltrative tumor growth.

Angiogenesis Inhibitors↗

PubMed2000

Retinoids inhibit human glioma cell proliferation and migration in primary cell cultures but not in established cell lines.

OBJECTIVE: Retinoids are known to exhibit a broad spectrum of biological activities, and they participate in the onset of differentiation and the inhibition of growth in a wide variety of cancer cells. Some of these vitamin A derivatives are already in clinical use. However, data on retinoid actions in glial tumors are rather sparse. Therefore, we studied the effects of the natural retinoic acid (RA) forms all-trans-RA, 9-cis-RA, and 13-cis-RA on glioma cell lines and primary cultures from patients with glioblastomas multiforme. METHODS: Six human glioma cell lines, one rat glioma cell line, and 20 primary cultures established from biopsies from patients with glioblastomas multiforme were investigated. Tumor cell proliferation was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and cell-counting assays. Random migration out of tumor spheroids was quantified using a video-morphometry system. Invasion was investigated using a confrontational coculture test system. Retinoid receptor (RA receptor [RAR]alpha, -beta, and -gamma and retinoid X receptor [RXR]alpha, -beta, and -gamma) expression status was determined using reverse transcription-polymerase chain reaction studies. RESULTS: Treatment of five human glioma cell lines with the different retinoids at concentrations up to 10(-5) mol/L produced no reduction of proliferation, using various incubation times. For one human glioma cell line (U343MG-A) and one rat glioma cell line (C6), which were previously reported to be sensitive to retinoids, we could confirm strong inhibitory effects on proliferation and clear changes in morphological features after retinoid treatment. Application of the different retinoids to low-passage primary cultures of human glioblastomas resulted in marked inhibition of proliferation (30-95%) for all tested samples. Using three-dimensional spheroid cultures, we detected retinoid-induced decreases in cell migration (24-65%). Invasion was not affected by these vitamin A derivatives. In an analysis of the expression patterns for retinoid receptors (RARs and RXRs), all primary culture samples yielded positive results for RAR gamma and RXR alpha and negative results for RAR alpha, RAR beta, and RXR gamma, whereas the results of RXR beta expression were heterogeneous among different patients. The cell lines, irrespective of their RA sensitivities, did not exhibit any major differences in receptor expression. CONCLUSION: Retinoids strongly inhibit proliferation and migration in primary cultures of human glioblastomas multiforme. Our data support a clinical trial of retinoids for the treatment of human malignant gliomas. We observed that most established cell lines were not sensitive to RA. This difference between long-term cell lines and primary cultures cannot be explained by different retinoid receptor expression patterns.

Adult↗

PubMed2000

Quantitative parameters of intraoperative electromyography predict facial nerve outcomes for vestibular schwannoma surgery.

OBJECTIVE: Facial nerve monitoring is an established method that is routinely used during cerebellopontine angle tumor surgery. The aim of this study was to determine quantitative electromyographic (EMG) parameters that were predictive of facial nerve outcomes. METHODS: In 137 patients with intra-/extrameatal vestibular schwannomas, the most proximal (the exit from the brainstem) and distal (the fundus of the internal auditory canal) parts of the facial nerve were stimulated after total tumor removal. A quantitative analysis of absolute values and ratios (proximal/distal) of evoked EMG parameters (amplitude, latency, and duration) was performed, and parameters were correlated with postoperative (1 and 6 wk and 6 mo) facial nerve function (FNF). RESULTS: Absolute values of EMG amplitudes were statistically correlated with FNF (P < 0.05). Amplitude ratios (proximal/distal) demonstrated an even greater predictive power. The risk of exhibiting facial palsy 6 months after surgery increased from 1.6% (amplitude ratio of >0.8) to 75% (ratio of <0.1). For EMG latencies, only the ratios revealed a significant correlation with FNF. The latency ratio-dependent risk of facial palsy after 6 months increased from 2.9% (ratio of <1.05) to 33% (ratio of >1.35). The durations of the muscle responses were not significantly correlated with clinical outcomes. CONCLUSION: The predictive power of the amplitudes and latencies of electrically evoked muscle responses could be improved by calculating proximal/distal ratios. The proximal/distal amplitude ratio proved to be the most powerful parameter for intraoperative assessment of postoperative FNF.

Adult↗

PubMed2000

Vascular endothelial growth factor-driven glioma growth and vascularization in an orthotopic rat model monitored by magnetic resonance imaging.

OBJECTIVE: The goal of the present study was to develop an orthotopic in vivo model for the investigation of vascular endothelial growth factor (VEGF)-dependent glioma growth and vascularization. METHODS: C6 glioma cells were infected with viruses encoding sense or antisense VEGF. Expression of the transgene was controlled by Northern blot analysis, Western blot analysis, and immunohistochemistry. Spheroids generated from both clones as well as from wild-type and mock-transfected cells were implanted in the brains of Sprague-Dawley rats. Growth and vascularization were assessed using magnetic resonance imaging after 7 and 11 days. Histology was studied using hematoxylin and eosin staining, immunohistochemistry with anti-von Willebrand staining, anti-VEGF, anti-CD8, and assessment of vessel density. RESULTS: Cell proliferation, migration, and invasion in vitro were very similar in all cell clones. Sense gliomas demonstrated by far the fastest growth in vivo, with intense contrast enhancement meeting criteria for highly malignant tumors. Histological examination revealed masses of von Willebrand- and VEGF-positive tumor vessels with a high vessel density. Antisense gliomas depicted the radiological features of low-grade gliomas, with slow growth and poor vascularization, although they were highly infiltrative. Wild-type and mock-transfected gliomas demonstrated similar growth and vascularization patterns intermediate between sense and antisense gliomas. Any influence of the allogeneic response of the hosts on different tumor sizes could be excluded. CONCLUSION: Our model elucidates glioma growth and vascularization as strongly VEGF dependent, which is consistent with human gliomas. Thus, this model is suitable for testing antiangiogenic strategies to interfere with the VEGF/VEGF receptor system, as well as for exploring VEGF-independent mechanisms using the antisense-transfected clone.

Animals↗

PubMed2000

Acoustic neuroma surgery as an interdisciplinary approach: a neurosurgical series of 508 patients.

OBJECTIVES: To evaluate an interdisciplinary concept (neurosurgery/ear, nose, and throat (ENT)) of treating acoustic neuromas with extrameatal extension via the retromastoidal approach. To analyse whether monitoring both facial nerve EMG and BAEP improved the functional outcome in acoustic neuroma surgery. METHODS: In a series of 508 patients consecutively operated on over a period of 7 years, functional outcome of the facial nerve was evaluated according to the House/Brackmann scale and hearing preservation was classified using the Gardner/Robertson system. RESULTS: Facial monitoring (396 of 508 operations) and continuous BAEP recording (229 of 399 cases with preserved hearing preoperatively) were performed routinely. With intraoperative monitoring, the rate of excellent/good facial nerve function (House/Brackmann I-II) was 88.7%. Good functional hearing (Gardner/Robertson 1-3) was preserved in 39.8%. CONCLUSION: Acoustic neuroma surgery via a retrosigmoidal approach is a safe and effective treatment for tumours with extrameatal extension. Functional results can be substantially improved by intraoperative monitoring. The interdisciplinary concept of surgery performed by ENT and neurosurgeons was particularly convincing as each pathoanatomical phase of the operation is performed by a surgeon best acquainted with the regional specialties.

Adolescent↗

PubMed2000

Treatment of progressive or recurrent pediatric malignant supratentorial brain tumors with herpes simplex virus thymidine kinase gene vector-producer cells followed by intravenous ganciclovir administration.

OBJECT: The outcome for children with recurrent malignant brain tumors is poor. The majority of patients die of progressive disease within months of relapse, and other therapeutic options are needed. The goal of this Phase I study was to evaluate the safety of in vivo suicide gene therapy in 12 children with recurrent, malignant, supratentorial brain tumors. METHODS: After optimal repeated tumor resection, multiple injections of murine vector-producing cells shedding murine replication-defective retroviral vectors coding the herpes simplex virus thymidine kinase type 1 (HSV-Tk1) gene were made into the rim of the resection cavity. Fourteen days after the vector-producing cells were injected, ganciclovir was administered for 14 days. The retroviral vector that was used only integrated and expressed HSV-Tk1 in proliferating cells, which are killed after a series of metabolic events lead to cell death. The median age of the patients was 11 years (range 2-15 years). Treated brain tumors included seven malignant gliomas, two ependyminomas, and three primitive neuroectodermal tumors. The patients were treated with one of three escalating dose concentrations of vector-producer cells. Four transient central nervous system adverse effects were considered possibly related to the vector-producing cells. In no child did permanent neurological worsening or ventricular irritation develop, and tests for replication-competent retroviruses yielded negative findings. CONCLUSIONS: This Phase I study demonstrates that in vivo gene therapy in which a replication-defective retroviral vector in murine vector-producing cells is delivered by brain injections can be performed with satisfactory safety in a select group of children with localized supratentorial brain tumors.

Adolescent↗

PubMed2000

MR spectroscopy in gliomatosis cerebri.

BACKGROUND AND PURPOSE: The diagnosis of gliomatosis cerebri with MR imaging is known to be difficult. We report on the value of MR spectroscopy in the diagnosis, grading, and biopsy planing in eight patients with histopathologically proved gliomatosis cerebri. METHODS: Patients underwent MR imaging and MR spectroscopy (single-voxel point-resolved spectroscopy [PRESS] at 1500/135, and chemical-shift imaging [CSI] PRESS at 1500/135) before open (n = 4) or stereotactic (n = 4) biopsy. In six patients who underwent CSI, biopsy samples were taken from regions of maximally elevated levels of choline/N-acetylaspartate (Cho/NAA). RESULTS: All patients showed elevated Cho/creatine (Cr) and Cho/NAA levels as well as varying degrees of decreased NAA/Cr ratios, which were most pronounced in the anaplastic lesions. In low-grade lesions, there was a maximum Cho/NAA ratio of 1.3, whereas in anaplastic tumors, the maximum Cho/NAA level was at least 2.5. Spectra in two patients with grade III lesions revealed a lactate peak; lactate and lipid signals were seen in two patients with grade IV lesions. Biopsy specimens from regions with maximally elevated levels of Cho/NAA showed dense infiltration of tumor cells. CONCLUSION: MR spectroscopy might be used to classify gliomatosis cerebri as a stable or a progressive disease indicating its potential therapeutic relevance.

Adolescent↗