Biomedical subjects

Walter A Hall

Publications and source records attributed to Walter A Hall.

At least 19 recordsLinked to original sources

PubMed2007

Intracranial therapy of glioblastoma with the fusion protein DTAT in immunodeficient mice.

A gene splicing technique was used to create a hybrid fusion protein DTAT encoding the 390 amino acid portion of diphtheria toxin (DT(390)), a linker, and the downstream 135-amino terminal fragment portion of human urokinase plasminogen activator. DTAT was assembled to target human glioblastoma cell lines in a murine intracranial model. Previously published in vitro studies demonstrated that DTAT was highly selective and toxic to human glioblastoma cell lines in a flank tumor model. The purpose of this study was to determine the toxicity, specificity and possible therapeutic efficacy of DTAT in an intracranial model. Convection enhanced delivery of DTAT resulted in about a 16-fold increase in maximum tolerated dose. Intracranial administration of DTAT on an every-other-day basis in nude mice with established U87 MG brain tumors resulted in significant reductions in tumor volume and significantly prolonged survival (p < 0.0001). Magnetic resonance imaging proved to be a powerful tool in mice and rats for demonstrating tumor growth in a xenograft intracranial model, assessing the efficacy of DTAT in tumor volume reduction and detecting DTAT-associated intracranial toxicity and vascular damage. These results suggest that the DTAT recombinant fusion protein is highly effective in an intracranial model and DTAT might be an effective treatment for glioblastoma.

Animals↗

PubMed2007

Efficacy of an osmotic pump delivered, GM-CSF-based tumor vaccine in the treatment of upper aerodigestive squamous cell carcinoma in rats.

PURPOSE: Upper aerodigestive tract (UADT) cancer has not experienced significant overall survival improvement for over 20 years, and no successful treatments for systemic disease exist. Most patients with UADT cancer experience immune suppression, therefore immune restorative therapies may offer promise for these patients. We presently tested the efficacy of granulocyte macrophage-colony stimulating factor (GM-CSF) delivered via 28-day continuous infusion pump, in combination with irradiated tumor cells, in a flank model of UADT cancer. METHODS: Five groups of rats were inoculated with syngeneic mucosally derived squamous carcinoma cells (FAT-7). Osmotic minipumps were implanted in the contralateral flank to deliver GM-CSF at 0 (PBS), 0.1, 1, 10, or 100 ng/day (n = 6 per group) for 28 days; 10(6) irradiated FAT-7 cells (ITC) were injected at the site of the GM-CSF infusion on days 0, 3, 7, 14, and 21 immune infiltrates in tumors were analyzed. RESULTS: Rats that received 10 or 100 ng/day GM-CSF/ITC had a significantly slower tumor growth rate compared to those who received 0, 0.1, or 1 ng/day (ANOVA, P < 0.01). There were increased CD 4+, CD 8+, and CD 68+ cells in tumors of GM-CSF/ITC treated animals over controls. CONCLUSION: GM-CSF (10 or 100 ng/day) delivered locally via osmotic pump with ITC slows the growth rate of mucosally derived squamous cell carcinoma in rats while improving immune cell infiltrates. The efficacy of locally delivered GM-CSF immunotherapy in this model may be a first step toward this immunotherapy strategy for humans.

Animals↗

PubMed2006

Expression of MHC I and NK ligands on human CD133+ glioma cells: possible targets of immunotherapy.

Mounting evidence suggests that gliomas are comprised of differentiated tumor cells and brain tumor stem cells (BTSCs). BTSCs account for a fraction of total tumor cells, yet are apparently the sole cells capable of tumor initiation and tumor renewal. BTSCs have been identified as the CD133-positive fraction of human glioma, whereas their CD133-negative daughter cells have limited proliferative ability and are not tumorogenic. It is well established that the bulk tumor mass escapes immune surveillance by multiple mechanisms, yet little is known about the immunogenicity of the CD133-positive fraction of the tumor mass. We investigated the immunogenicity of CD133-positive cells in two human astrocytoma and two glioblastoma multiforme samples. Flow cytometry analyses revealed that the majority of CD133-positive cells do not express detectable MHC I or natural killer (NK) cell activating ligands, which may render them resistant to adaptive and innate immune surveillance. Incubating CD133-positive cells in interferon gamma (INF-gamma) significantly increased the percentage of CD133-positive cells that expressed MHC I and NK cell ligands. Furthermore, pretreatment of CD133-positive cells with INF-gamma rendered them sensitive to NK cell-mediated lysis in vitro. There were no consistent differences in immunogenicity between the CD133-positive and CD133-negative cells in these experiments. We conclude that CD133-posistive and CD133-negative glioma cells may be similarly resistant to immune surveillance, but that INF-gamma may partially restore their immunogenicity and potentiate their lysis by NK cells.

AC133 Antigen↗

PubMed2006

Delivery of chemotherapy and antibodies across the blood-brain barrier and the role of chemoprotection, in primary and metastatic brain tumors: report of the Eleventh Annual Blood-Brain Barrier Consortium meeting.

Although knowledge of molecular biology and cellular physiology has advanced at a rapid pace, much remains to be learned about delivering chemotherapy and antibodies across the blood-brain barrier (BBB) for the diagnosis and treatment of central nervous system (CNS) disease. A meeting, partially funded by an NIH R13 grant, was convened to discuss the state of the science, current knowledge gaps, and future directions in the delivery of drugs and proteins to the CNS, for the treatment of primary and metastatic brain tumors. Meeting topics included CNS metastases and the BBB, and chemoprotection and chemoenhancement in CNS disorders. The discussions regarding CNS metastases generated possibilities of chemoprotection as a means not only to decrease treatment-related toxicity but also to increase chemotherapy dose intensity. The increasing incidence of sanctuary brain metastasis from breast cancer, in part due to the difficulty of monoclonal antibodies (mAbs) such as herceptin to cross the BBB, was one of the most salient "take home" messages of the meeting.

Animals↗

PubMed2006

Intracranial therapy of glioblastoma with the fusion protein DTIL13 in immunodeficient mice.

A fusion protein consisting of human interleukin-13 and the first 389 amino acids of diphtheria toxin was assembled in order to target human glioblastoma cell lines in a murine intracranial model. In vitro studies to determine specificity indicated that the protein called DTIL13 was highly selective for human glioblastoma. In vivo, the maximum tolerated dose of DTIL13 was 1 microg/injection given every other day and repeated for 3 days. Doses that exceeded this amount resulted in weight loss and liver damage as determined by histology and enzyme assay. Experiments in IL-4 receptor knockout mice revealed that liver toxicity was receptor-related. This same dose given to nude mice with established U373 MG brain tumors resulted in significant reductions in tumor volume and significantly prolonged survival (p<0.0001). Magnetic resonance imaging (MRI) proved to be extremely useful in (i) determining the ability of DTIL13 to reduce tumor size and (ii) for studying toxicity since diffusion-weighted and gradient echo-weighted MRI revealed that vascular leak syndrome was not a limiting toxicity at this dose. These results suggest that DTIL13 is as effective in an intracranial rodent model as it was in a flank model in previous studies and that DTIL13 might be an effective treatment for glioblastoma multiforme.

Animals↗

PubMed2006

Efficacy of antiangiogenic targeted toxins against glioblastoma multiforme.

OBJECT: Because the prognosis for patients with glioblastoma multiforme (GBM) remains poor, investigators have focused on developing new and more effective treatment modalities. Targeted toxins represent a new class of compounds composed of a potent protein toxin and a carrier ligand that will recognize cell surface antigens located on target tissue. A recombinant fusion protein was created that contains the translocation and catalytic portions of diphtheria toxin that are responsible for cell entry and killing, respectively, fused to the noninternalizing aminoterminal fragment portion of human plasminogen activator. This diptheria toxin-uPA fusion protein (DTAT) has the advantage over other fusion proteins of targeting malignant glioma cells and the endothelial cells of the neovasculature that express the urokinase-type plasminogen activator receptor (uPAR). Another protein, DTAT13, was synthesized to target uPAR on the neovasculature and the uPAR and interleukin-13 receptor-expressing GBM cells. The authors describe the in vitro and in vivo efficacy of DTAT and DTAT13 against GBM. METHODS: The in vitro cytotoxicity of DTAT and DTAT13 was measured using cell proliferation assays. In vivo studies were performed in which DTAT, DTAT13, or a control protein was injected directly into GBM flank tumors in athymic nude mice. Tumor volume was assessed over time and analyzed using the Student t-test. The systemic organ effects of DTAT and DTAT13 were examined functionally and histologically in tumor-free C57BL/6 mice. In vitro, DTAT and DTAT13 were found to be highly potent and selective against U118MG, U87MG, and U373MG GBM cell lines and human umbilical vein endothelial cells. In vivo, DTAT and DTAT13 both caused a statistically significant (p < 0.05) regression of U87MG GBM flank tumors when administered every other day at 10 mg/day for five doses. No tumor regression was seen in control animals. Both DTAT and DTAT13 had little effect on histological findings in the liver, kidney, spleen, and lungs. Serum analysis did not demonstrate an effect on blood urea nitrogen levels, but liver alanine aminotransferase levels rose to statistically significant (p = 0.046) but not life-threatening levels. Also, DTAT13 was less toxic than DTAT in studies of mortality rates. CONCLUSIONS: Both DTAT and DTAT13 might have potential for clinical application against GBM because of their ability to target both the tumor cells and neovasculature simultaneously with an absence of serious systemic side effects. The discovery that DTAT13 was less toxic than DTAT indicated that the bispecific fusion protein might target a broader subset of antigenetically diverse patients with tumors while reducing the systemic exposure to toxin that would be necessary if two agents were administered separately.

Angiogenesis Inhibitors↗

PubMed2006

Convection-enhanced delivery: targeted toxin treatment of malignant glioma.

Historically, malignant gliomas are perhaps the most difficult intracranial neoplasms to treat. Surgery, radiation therapy, and traditional chemotherapy have not been able to significantly alter the course of this disease. By definition, these tumors are located in the protected space of the cranial vault, where the blood-brain barrier prevents most therapies from gaining access. Because of the difficulty in treating this disease, new, innovative treatments and alternative delivery techniques for those therapies are needed. Targeted toxins are fusion proteins that represent a novel medical treatment for these cancers that is under development. However, the efficacy of these agents is dependent on the method of delivery to the tumor. The administration of targeted toxins requires image-guided placement of catheters, either within the tumor or into the adjacent infiltrated brain, and positive pressure infusion. The term that has been applied to this microinfusion technique is convection-enhanced delivery (CED). This infusion method was first attempted via direct intratumoral infusion in nude mouse flank tumor models of human malignant glioma. After significant development of this delivery technique in animal models, the successful demonstration of in vivo efficacy of targeted toxins in Phase I and II clinical trials was reported. Currently, ongoing targeted toxin trials are being conducted at academic health centers to define the best clinical practice for CED. This work involves refining the details of delivery such as infusion rate, duration of treatment, and drug dosing. The early results of CED of targeted toxins supports their continued investigation, as few other treatment modalities have produced durable results in the fight against gliomas.

Animals↗

PubMed2006

Identification of EGFRvIII-derived CTL epitopes restricted by HLA A0201 for dendritic cell based immunotherapy of gliomas.

The type III variant of the epidermal growth factor receptor (EGFRvIII) mutation is present in 20-25% of patients with glioblastoma multiforme (GBM). EGFRvIII is not expressed in normal tissue and is therefore a suitable candidate antigen for dendritic cell (DC) based immunotherapy of GBM. To identify the antigenic epitope(s) that may serve as targets for EGFRvIII-specific cytotoxic T lymphocytes (CTLs), the peptide sequence of EGFRvIII was screened with two software programs to predict candidate epitopes restricted by the major histocompatibility complex class I subtype HLA-A0201, which is the predominant subtype in most ethnic groups. Three predicted peptides were constructed and loaded to mature human DCs generated from peripheral blood monocytes. Autologous CD8+ T cells were stimulated in vitro with the EGFRvIII peptide-pulsed DCs. One of the three peptides was found to induce EGFRvIII-specific CTLs as demonstrated by IFN-gamma production and cytotoxicity against HLA-A0201+ EGFRvIII transfected U87 glioma cells. These results suggest that vaccination with EGFRvIII peptide-pulsed DCs or adoptive transfer of in vitro elicited EGFRvIII-specific CTLs by EGFRvIII peptide-pulsed DCs are potential approaches to the treatment of glioma patients.

Brain Neoplasms↗

PubMed2006

Immunotoxin pharmacokinetics: a comparison of the anti-glioblastoma bi-specific fusion protein (DTAT13) to DTAT and DTIL13.

DTAT13, a novel recombinant bispecific immunotoxin (IT) consisting of truncated diphtheria toxin, an amino-terminal (AT) fragment of the urokinase-type plasminogen activator (uPa), and a fragment of human IL-13 was assembled in order to target receptors on glioblastoma multiforme (GBM) and its associated neovasculature. Previous in vitro studies confirmed the efficacy of DTAT13 against various GBM cell lines expressing both IL-13 receptor or uPA receptor, and previous in vivo testing demonstrated the efficacy of DTAT13 in significantly inhibiting a range of xenograft tumors and showed that DTAT13 was 160- and 8-fold less toxic to the parental fusion IT, DTAT and DTIL13, respectively. To further understand the properties of DTAT13, pharmacokinetic/biodistribution experiments were performed. Binding analysis revealed that the IL-13 domain functioned independently of the uPA domain and that the K (d) for each binding domain was essentially the same as that of DTIL13 and DTAT. Flow cytometry studies indicated that DTAT13 bound better than DTAT or DTIL13. Analysis of the rate of protein synthesis inhibition in U87 MG cells by DTAT13 compared to DTAT revealed a faster rate of inhibition with DTAT13 compared to DTAT. The rate of protein synthesis inhibition of DTAT13 was identical to that of DTIL13 in U373 MG cells. Intracranial biodistribution studies revealed that DTAT13 was able to cross to the contralateral hemisphere unlike DTIL13 but similar to DTAT. These studies show that DTAT13 has properties encompassing those of both DTIL13 and DTAT and warrants further consideration for clinical development.

Animals↗

PubMed2006

Intraoperative magnetic resonance imaging-guided neurosurgery at 3-T.

OBJECTIVE: Between 1997 and 2004, more than 700 neurosurgical procedures were performed in a 1.5-T magnetic resonance-guided therapy suite. During this period, the concept of high-field intraoperative magnetic resonance imaging (MRI) was validated, as was a new surgical guidance tool, the Navigus (Image-guided Neurologics, Melbourne, FL), and its methodology, prospective stereotaxy. Clinical protocols were refined to optimize surgical techniques. That implementation, the "Minnesota suite," has recently been revised, and a new suite with a 3-T MRI scanner has been developed. METHODS: On the basis of experience at the initial 1.5-T suite, a new suite was designed to house a 3-T MRI scanner with wide surgical access at the rear of the scanner (opposite the patient couch). Use of electrocautery, a fiberoptic headlamp, a power drill, and MRI-compatible neurosurgical cutlery was anticipated by inclusion of waveguides and radiofrequency filter panels that penetrate the MRI suite's radiofrequency shield. An MRI-compatible head holder was adapted for use on the scanner table. A few items exhibiting limited ferromagnetism were used within the magnetic field, taking strict precautions. RESULTS: During the initial procedures (all magnetic resonance-guided neurobiopsies), the new suite functioned as anticipated. Although metallic artifact related to titanium needles is more challenging at 3 T than at 1.5 T, it can be contained even at 3 T. Similar to 1.5 T, such artifact is best contained when the device is oriented along B0, the main magnetic field. Surgical needles, disposable scalpels, and disposable razors, despite being minimally ferromagnetic, were easily controlled by the surgeon. CONCLUSION: An intraoperative magnetic resonance-guided neurosurgical theater has been developed with a 3-T MRI scanner. Intraoperative imaging is feasible at this field strength, and concerns regarding specific absorption rate can be allayed. Infection control procedures can be designed to permit neurosurgery within this environment. Despite the increase in magnetic field strength, safety can be maintained.

Brain Diseases↗

PubMed2006

Convection-enhanced delivery of targeted toxins for malignant glioma.

Malignant gliomas represent a difficult treatment challenge for the neuro-oncologist and the neurosurgeon. These tumours continue to be refractory to standard therapies, such as surgery, radiotherapy and conventional chemotherapy, and new therapeutic options are clearly needed. Therefore, investigators have recently taken a new direction and started to engineer compounds such as recombinant cytotoxins, antiangiogenesis factors and genetic delivery vectors. However, these promising new agents are all dependent on an effective distribution method in order to bypass the blood-brain barrier. Convection-enhanced delivery (CED) allows for the administration of targeted toxins and other agents directly into the brain at the site of a tumour via catheters placed with the aid of stereotactic or image-guided surgery. The use of this technique is gaining momentum as a newly accepted treatment modality where little else has produced durable results in the fight against gliomas. Direct intratumoural infusion was first performed in nude mouse flank tumour models of human malignant glioma. After significant testing in preclinical animal studies, this method of delivery was followed by the successful demonstration of in vivo efficacy in Phase I and II clinical trials. Currently, this technique is being used in the investigational setting at academic medical centres where investigators are starting to define the best practice for CED. Fundamental issues in this method of delivery such as rate of infusion, cannula size, infusate concentration and tissue-cannula sealing time shape the current discussion in the literature. Targeted toxin therapy represents one of the newest and most promising treatments for this unfortunate patient population, with proven clinical efficacy administered through CED, which is a novel approach to drug delivery.

Animals↗

PubMed2005

Osmotic blood-brain barrier disruption chemotherapy for diffuse pontine gliomas.

The prognosis for patients with diffuse pontine gliomas (DPG) remains poor. New aggressive innovative treatments are necessary to treat this disease. From 1984 to 1998, eight patients (4M/4F), median age 11 years, with DPG were treated with monthly osmotic blood-brain barrier disruption (BBBD) chemotherapy using intraarterial carboplatin or methotrexate and intravenous cytoxan and etoposide. Patients presented for a median duration of 6 weeks with increased intracranial pressure, long tract signs, diplopia, ataxia, and nausea/vomiting. DPG was demonstrated on magnetic resonance (MR) imaging in seven patients and on CT in one. Two patients had biopsies that showed an astrocytoma and an anaplastic astrocytoma. Three tumors enhanced on MR imaging after contrast administration. Three patients had radiation therapy before BBBD chemotherapy and four afterwards. Two patients had chemotherapy (tamoxifen, topotecan) before BBBD chemotherapy and two afterwards. In general, patients were evaluated with MR imaging every 3 months to monitor for a response to treatment. The median number of chemotherapy cycles that were administered by BBBD was 10, mean 10. Three patients also received one, two, or three cycles of intraarterial chemotherapy without BBBD. One patient that was started on carboplatin was converted to methotrexate, and five that were started on the methotrexate protocol were later converted over to carboplatin. One patient received monthly methotrexate followed by 14 days of procarbazine and one patient started on methotrexate was switched to navelbine. MR imaging demonstrated two partial responses, five patients with stable disease, and one with disease progression. The median time to tumor progression was 15 months with the range from <1 to 40 months. The median survival from the time of diagnosis was 27 months, ranging from 7 to 80 months. The median survival time from the first BBBD or intraarterial treatment was 16.5 months, ranging from 5 to 69 months. One patient was lost to follow-up with an unknown date of death. Although the sample size is small, the TTP and survival times are longer than those previously reported in other DPG series. In addition, the ability to demonstrate stable disease or partial responses in DPG on MR imaging argues for the therapeutic benefit of BBBD chemotherapy. The enhanced delivery of chemotherapy afforded by osmotic BBBD supports the further examination of this treatment modality for patients with DPG.

Adolescent↗

PubMed2005

3-Tesla intraoperative MR imaging for neurosurgery.

Intraoperative magnetic resonance (MR) image-guided neurosurgery has been performed since 1994. Using a 1.5-Tesla (T) intraoperative MR imaging system, we have performed more than 750 interventional procedures. Having validated the safety and efficacy of this surgical technique that is relatively amenable to nearly all new in-hospital MR suites, we sought to adapt this approach at our sister hospital where a new short-bore 3-T MR suite was being installed. Using many of the lessons learned from our initial experience at 1.5-T, we designed a new interventional suite that would enable surgery to be performed entirely within a 3-T MR environment. All surgical instrumentation including electrocautery, fiberoptic headlamp, power drill, and ultrasonic aspirator was entirely MR-compatible. A few items with limited ferromagnetism were utilized within the magnetic field under strict precaution. From 2/04 to 7/05, those cases initially performed within the 3-T surgical suite included one drainage and reservoir placement for a cystic craniopharyngioma, five brain biopsies and two craniotomies; one for open brain biopsy and another for lesion resection. The craniopharyngioma was successfully aspirated and had the reservoir catheter placed within the cyst. All five brain biopsies yielded diagnostic tissue. The craniotomy for mass resection demonstrated radiation necrosis. Although the metallic artifact from the biopsy needle was more prominent than at 1.5-T, accurate image interpretation was possible. Surgical needles, disposable scalpel, disposable razor, and surgical stapler were minimally ferromagnetic and safely controlled by the surgeon. There were no adverse events associated with any procedure. MR-guided neurosurgery can be safely and effectively performed at 3-T. The surgical environment at 3-T is comparable to that present at 1.5-T.

Adult↗

PubMed2005

New frontiers in translational research in neuro-oncology and the blood-brain barrier: report of the tenth annual Blood-Brain Barrier Disruption Consortium Meeting.

The blood-brain barrier (BBB) presents a major obstacle to the treatment of malignant brain tumors and other central nervous system (CNS) diseases. For this reason, a meeting partially funded by an NIH R13 grant was convened to discuss recent advances and future directions in translational research in neuro-oncology and the BBB. Cell biology and transport across the BBB, delivery of agents to the CNS, neuroimaging, angiogenesis, immunotherapy, and gene therapy, as well as glioma, primary CNS lymphoma, and metastases to the CNS were discussed. Transport across the BBB relates to the neurovascular unit, which consists not only of endothelial cells but also of pericyte, glia, and neuronal elements.

Antineoplastic Agents↗

PubMed2005

Long-term follow-up of trigeminal neuralgia treatment using a linear accelerator.

While most of the studies examining radiosurgery for trigeminal neuralgia have used a Gamma Knife, a linear accelerator can also be utilized for treatment. We report on 20 patients with trigeminal neuralgia who received 23 treatments with a linear accelerator that delivered a maximum dose of 82.3-100 Gy. The median patient follow-up was 56.5 months, 70% of patients had received previous surgical treatment and 20% had secondary (nonessential) trigeminal neuralgia. Eight (35%) radiosurgery treatments resulted in complete pain relief; 5 (63%) patients with initial pain relief had pain recurrence at a mean time of 21.5 months. Ten (43%) patients reported a 50% or more decrease in pain severity but have not achieved a pain-free state. A total of 18 (78%) treatments resulted in no pain or a 50% or greater improvement in pain. Five treatments (22%) resulted in less than 50% improvement in pain. We conclude that linear accelerator stereotactic radiosurgery is a viable treatment option for trigeminal neuralgia patients, especially for patients who have not had a previous invasive treatment.

Adult↗

PubMed2005

Intraoperative MR imaging.

With the rapid evolution of technologic advances in neurosurgery, it is no surprise that the use of MR imaging to guide the performance of safe and effective surgical procedures is at the forefront of development. This article highlights the current capabilities of intraoperative MR-guided surgery for a variety of neurosurgical procedures and traces the evolution of the field to its present level of technical sophistication. The costs of intraoperative MR imaging and its future directions are discussed.

Biopsy↗

PubMed2005

1.5 T: spectroscopy-supported brain biopsy.

The technique for performing brain biopsy has evolved significantly over the last three decades. Intraoperative MRI guidance has enhanced the diagnostic rate for brain biopsy by now allowing neurosurgeons to compensate for brain shift while performing the procedure in near-real time. The development of a trajectory guide enables the neurosurgeon to determine a safe and accurate path for intraoperative MRI-guided brain biopsy and to secure the position of the needle within the target tissue. Magnetic resonance spectroscopy (MRS) has been used to help distinguish recurrent brain tumor from the effect of previous treatments by measuring specific metabolites within the area of concern. Combining the use of a trajectory guide with MRS should enhance the diagnostic yield for MRI-guided brain biopsy.

Biopsy↗

PubMed2005

Functional magnetic resonance imaging-guided resection of low-grade gliomas.

BACKGROUND: We sought to determine the safety and efficacy of using functional magnetic resonance imaging (fMRI) to guide the resection of low-grade gliomas (LGG). METHODS: From September 1997 to February 2003, fMRI was performed in 16 patients (age, 15-43 years) before an attempted surgical resection of LGG. Functional imaging was used to identify and coregister eloquent cortices pertinent to motor (10), speech (3), motor and speech (2), and short-term memory and speech (1) activation with respect to the tumor using a 1.5-T interventional MRI system. Intraoperatively acquired T(2)-weighted and turbo-fluid attenuated inversion recovery images were used to assess the completeness of surgical resection. RESULTS: Tumors included 10 oligodendrogliomas, 4 astrocytomas, 1 dysembryoplastic neuroepithelial tumor, and 1 pleomorphic xanthoastrocytoma. In every case, the preoperative brain activation study accurately determined the location of neurologic function. After surgery, one patient had a transient hemiparesis and another had a temporary apraxia. Ten patients had radiographically complete resections and 5 with oligodendrogliomas had incomplete resections because of the proximity of their tumors to functional areas. Only one patient with an astrocytoma in the motor strip received postoperative radiation therapy. To date, radiographic tumor progression has not been seen in any patient with either a partial or a complete resection with a median follow-up of 25 months (range, 12-87 months). CONCLUSIONS: Functional MRI was accurate for identifying areas of neurologic function before surgical resection of LGG. Patients with complete radiographic resections or with incompletely resected oligodendrogliomas can be safely followed radiographically after surgery. Radiation therapy was reserved for infiltrating astrocytomas that were not completely resectable.

Adolescent↗