Bio

Clinical Focus


  • Neurological Surgery
  • Neuro-Oncology
  • Pediatric Vascular Disease
  • Neurosurgery
  • Brain and Spinal Cord Tumors

Academic Appointments


Administrative Appointments


  • Endowed Professor, Neurosurgery & Pediatric Neurosurgery (2004 - Present)
  • Division Chief, Pediatric Neurosurgery (2004 - Present)
  • Director, Regional Pediatric Neurosurgery (2004 - Present)
  • Co-Director Children's Brain Tumor Center, Neuroscience Institute (2007 - Present)

Honors & Awards


  • President, California Association of Neurosurgeons (2005-2006)
  • Preuss Award, Congress of Neurological Surgeons (1987)
  • Distinguished Achievement Award, Hydrocephalus Association (July 2008)

Professional Education


  • Fellowship:Univ of California San Francisco (1978) CA
  • Internship:Tulane University School of Medicine (1971) LA
  • Residency:Tulane University (1977) LA
  • Board Certification: Pediatric Neurological Surgery, American Board of Pediatric Neurological Surgery (1996)
  • Board Certification: Neurological Surgery, American Board of Neurological Surgery (1980)
  • Medical Education:Tulane University School of Medicine (1970) LA
  • Fellowship, University of CA, San Francisco, Neuro-Oncology (1978)
  • Medicine, Tulane University, Neurosurgery (1976)
  • MD, Tulane University, Medicine (1970)

Research & Scholarship

Clinical Trials


  • Phase I Rindopepimut After Conventional Radiation in Children w/ Diffuse Intrinsic Pontine Gliomas Not Recruiting

    This is a research study of patients with diffuse intrinsic pontine gliomas. We hope to learn about the safety and efficacy of treating pediatric diffuse intrinsic pontine glioma patients with the EGFRvIII peptide vaccine after conventional radiation.

    Stanford is currently not accepting patients for this trial. For more information, please contact Christina Huang, 650-723-0574.

    View full details

Teaching

2013-14 Courses


Publications

Journal Articles


  • Hedgehog-responsive candidate cell of origin for diffuse intrinsic pontine glioma PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Monje, M., Mitra, S. S., Freret, M. E., Raveh, T. B., Kim, J., Masek, M., Attema, J. L., Li, G., Haddix, T., Edwards, M. S., Fisher, P. G., Weissman, I. L., Rowitch, D. H., Vogel, H., Wong, A. J., Beachy, P. A. 2011; 108 (11): 4453-4458

    Abstract

    Diffuse intrinsic pontine gliomas (DIPGs) are highly aggressive tumors of childhood that are almost universally fatal. Our understanding of this devastating cancer is limited by a dearth of available tissue for study and by the lack of a faithful animal model. Intriguingly, DIPGs are restricted to the ventral pons and occur during a narrow window of middle childhood, suggesting dysregulation of a postnatal neurodevelopmental process. Here, we report the identification of a previously undescribed population of immunophenotypic neural precursor cells in the human and murine brainstem whose temporal and spatial distributions correlate closely with the incidence of DIPG and highlight a candidate cell of origin. Using early postmortem DIPG tumor tissue, we have established in vitro and xenograft models and find that the Hedgehog (Hh) signaling pathway implicated in many developmental and oncogenic processes is active in DIPG tumor cells. Modulation of Hh pathway activity has functional consequences for DIPG self-renewal capacity in neurosphere culture. The Hh pathway also appears to be active in normal ventral pontine precursor-like cells of the mouse, and unregulated pathway activity results in hypertrophy of the ventral pons. Together, these findings provide a foundation for understanding the cellular and molecular origins of DIPG, and suggest that the Hh pathway represents a potential therapeutic target in this devastating pediatric tumor.

    View details for DOI 10.1073/pnas.1101657108

    View details for Web of Science ID 000288450900040

    View details for PubMedID 21368213

  • Fronto-orbital advancement using an en bloc frontal bone craniectomy. Neurosurgery Guzman, R., Looby, J. F., Schendel, S. A., Edwards, M. S. 2011; 68 (1): 68-74

    Abstract

    Fronto-orbital advancement is a procedure commonly performed in craniofacial centers for coronal and metopic suture synostosis. Several variations of the technique have been reported.To describe our modifications to the anterior cranioplasty procedure and the results of our surgical series.Using our craniofacial database, we retrospectively analyzed the records of all patients undergoing fronto-orbital advancement for craniosynostosis. The same team of neurosurgeons and plastic surgeons performed all procedures. Demographic data, operative time, blood loss, length of stay, and clinical outcome were analyzed.Of 248 patients treated for craniosynostosis, a total of 70 patients underwent fronto-orbital advancement. Nineteen presented with metopic, 26 with unilateral coronal, 17 with bilateral coronal, and 8 with multiple synostosis. Median age at surgery was 6.5 months. Mean operative time was 210 minutes; mean blood loss was 167 mL; and length of stay was 4.5 days. A positive correlation was found between operative time and blood loss (r = 0.1, P < .01) and age at surgery and blood loss (r = 0.3, P < .0001). There was a minor morbidity rate of 2.9%. A good reconstruction was obtained in all patients using our en bloc fronto-orbital advancement without any midline osteotomies at a mean follow-up of 15 months.A team approach and the application of a standardized surgical technique should make it safer to operate in young children, shorten the surgical time, and lead to a reduction in blood loss. Reconstructing the frontal bone as an entire unit yielded excellent correction for coronal and metopic synostosis.

    View details for DOI 10.1227/NEU.0b013e31820780cd

    View details for PubMedID 21206324

  • Epilepsy surgery following brain tumor resection in children Clinical article JOURNAL OF NEUROSURGERY-PEDIATRICS Tian, A. G., Edwards, M. S., Williams, N. J., Olson, D. M. 2011; 7 (3): 229-234

    Abstract

    Intractable epilepsy following successful brain tumor surgery in children may have several underlying causes such as residual tumor, cortical dysplasia, and gliosis. The authors reviewed the cases of children who had previously undergone resection of a brain tumor only to have medically refractory seizures postoperatively.The authors performed a retrospective case review of 9 children who underwent brain tumor surgery 2-13 years before undergoing a second surgery to try and control their seizures.Eight of 9 children had seizures at the time of tumor presentation. Tumor types included ganglioglioma, dysembryoplastic neuroepithelial tumor, pilocytic astrocytoma, oligodendroglioma, ependymoma, and choroid plexus papilloma. All patients achieved a seizure-free interval before intractable seizures recurred. After the second operation, 3 children were seizure free, 1 only had auras, 2 had rare complex partial seizures, and 3 continued to have relatively frequent seizures, although the frequency and severity were reduced. Seven of 9 patients had pathology showing residual tumor.Epilepsy surgery following earlier brain tumor surgery can provide substantial benefit with reduced seizure number and severity. Despite reassuring brain imaging results, residual tumor was present more often than expected in pathological specimens.

    View details for DOI 10.3171/2010.12.PEDS10293

    View details for Web of Science ID 000287676800004

    View details for PubMedID 21361758

  • Primary Pediatric Skull Tumors PEDIATRIC NEUROSURGERY Gephart, M. G., Colglazier, E., Paulk, K. L., Vogel, H., Guzman, R., Edwards, M. S. 2011; 47 (3): 198-203

    Abstract

    To review the pathological distribution of pediatric primary skull tumors, and to determine the diagnostic value of lesion location, patient age and lesion size.A retrospective chart review identified 51 consecutive pediatric patients with 54 primary skull tumors, treated between 2005 and 2010.The most common diagnoses were dermoid cysts (n = 34) and fibrous dysplasia (n = 5). While dermoid tumors could reside anywhere (sensitivity = 0.41), a midline lesion had a specificity of 0.9 and a positive predictive value of 0.88. All of the fibrous dysplasia lesions were laterally placed, with a negative predictive value (NPV) of 1. Patient age < or >5 years had a high sensitivity and NPV for dermoid cysts and fibrous dysplasia, respectively. Size appeared to be sensitive (0.91, 0.8), but not specific (0.6, 0.78), with good NPV (0.8, 0.97) when considering dermoid cysts (?2 cm) or fibrous dysplasia (>2 cm), respectively.Dermoid cysts followed by fibrous dysplasia are the most common primary skull tumors. Lesion location, patient age and lesion size give important clues as to the diagnosis. For the majority of cases, a clinical diagnosis based on CT is sufficient for presurgical evaluation.

    View details for DOI 10.1159/000330544

    View details for Web of Science ID 000300098800006

    View details for PubMedID 22301489

  • Stereotactic radiosurgery for pediatric intracranial arteriovenous malformations: the University of California at San Francisco experience JOURNAL OF NEUROSURGERY Smyth, M. D., Sneed, P. K., Ciricillo, S. F., Edwards, M. S., Wara, W. M., Larson, D. A., Lawton, M. T., Gutin, P. H., McDermott, M. W. 2002; 97 (1): 48-55

    Abstract

    Stereotactic radiosurgery for arteriovenous malformations (AVMs) is an accepted treatment option, but few reports have been published on the results of this treatment in children. In this study the authors describe a series of pediatric patients with a minimum follow-up duration of 36 months.From 1991 to 1997, 40 children (26 boys and 14 girls) with AVMs were treated with radiosurgery at the University of California at San Francisco (UCSF). Follow-up information was available for 31 children (20 boys and 11 girls) in whom the median age at initial treatment was 11.2 years (range 3.4-17.5 years). The median follow-up duration was 60 months (range 6-99 months). Sixteen percent of the AVMs were Spetzler-Martin Grade II; 68%, Grade III; 10%, Grade IV; and 6%, Grade V. The mean volume of the AVMs was 5.37 cm3 and the median volume was 1.6 cm3. The mean marginal dose of radiation was 16.7 Gy and the median dose was 18 Gy (range 12-19 Gy). Angiography performed in 26 children confirmed obliteration of the AVM nidus in nine patients (35%), partial response in 16 patients (62%), and no response in one patient (4%). In five patients who refused angiography, magnetic resonance (MR) imaging revealed obliteration in two patients and partial response in three patients, bringing the overall obliteration rate associated with initial radiosurgery to 35%. Logistic regression analysis confirmed a significant correlation between marginal dose prescription and response (p = 0.025); in AVMs that received at least 18 Gy there was a 10-fold increase in the obliteration rate (63%) over AVMs that received a lower dose. Lesions smaller than 3 cm3 were associated with a six-fold increased obliteration rate (53%) over lesions larger than 3 cm3 (8%), but AVM volume was not a statistically significant predictor of response (p = 0.09). Twelve patients have since undergone repeated radiosurgery and are currently being followed up with serial MR imaging studies (in five cases, the AVM is now obliterated). During the follow-up period (1918 patient-months) there were eight hemorrhages in five patients, with a cumulative posttreatment hemorrhage rate of 3.2%/patient/year in the 1st year and a rate of 4.3%/patient/year over the first 3 years. There were two permanent neurological complications (6%) and no deaths in this study.The lower overall obliteration rate reported in this series is most likely due to the larger mean AVM volumes treated at UCSF as well as conservative dose-volume prescriptions delivered to children. Significantly higher obliteration rates were observed when a marginal radiation dose of at least 18 Gy was delivered. The permanent complication rate is low and should encourage those treating children to use doses similar to those used in adults.

    View details for Web of Science ID 000176665000008

    View details for PubMedID 12134932

  • Prognostic role for diffusion-weighted imaging of pediatric optic pathway glioma. Journal of neuro-oncology Yeom, K. W., Lober, R. M., Andre, J. B., Fisher, P. G., Barnes, P. D., Edwards, M. S., Partap, S. 2013; 113 (3): 479-483

    Abstract

    Optic pathway glioma (OPG) has an unpredictable course, with poor correlation between conventional imaging features and tumor progression. We investigated whether diffusion-weighted MRI (DWI) predicts the clinical behavior of these tumors. Twelve children with OPG (median age 2.7 years; range 0.4-6.2 years) were followed for a median 4.4 years with DWI. Progression-free survival (time to requiring therapy) was compared between tumors stratified by apparent diffusion coefficient (ADC) from initial pre-treatment scans. Tumors with baseline ADC greater than 1,400 × 10(-6) mm(2)/s required treatment earlier than those with lower ADC (log-rank p = 0.002). In some cases, ADC increased leading up to treatment, and declined following treatment with surgery, chemotherapy, or radiation. Baseline ADC was higher in tumors that eventually required treatment (1,562 ± 192 × 10(-6) mm(2)/s), compared with those conservatively managed (1,123 ± 114 × 10(-6) mm(2)/s) (Kruskal-Wallis test p = 0.013). Higher ADC predicted earlier tumor progression in this cohort and in some cases declined after therapy. Evaluation of OPG with DWI may therefore be useful for predicting tumor behavior and assessing treatment response.

    View details for DOI 10.1007/s11060-013-1140-4

    View details for PubMedID 23673514

  • Diffusion-Weighted MRI: Distinction of Skull Base Chordoma from Chondrosarcoma. AJNR. American journal of neuroradiology Yeom, K. W., Lober, R. M., Mobley, B. C., Harsh, G., Vogel, H., Allagio, R., Pearson, M., Edwards, M. S., Fischbein, N. J. 2013; 34 (5): 1056-1061

    Abstract

    Chordoma and chondrosarcoma of the skull base are rare tumors with overlapping presentations and anatomic imaging features but different prognoses. We hypothesized that these tumors might be distinguished by using diffusion-weighted MR imaging.We retrospectively reviewed 19 patients with pathologically confirmed chordoma or chondrosarcoma who underwent both conventional and diffusion-weighted MR imaging. Differences in distributions of ADC were assessed by the Kruskal-Wallis test. Associations between histopathologic diagnosis and conventional MR imaging features (T2 signal intensity, contrast enhancement, and tumor location) were assessed with the Fisher exact test.Chondrosarcoma was associated with the highest mean ADC value (2051 ± 261 × 10(-6) mm(2)/s) and was significantly different from classic chordoma (1474 ± 117 × 10(-6) mm(2)/s) and poorly differentiated chordoma (875 ± 100 × 10(-6) mm(2)/s) (P < .001). Poorly differentiated chordoma was characterized by low T2 signal intensity (P = .001), but other conventional MR imaging features of enhancement and/or lesion location did not reliably distinguish these tumor types.Diffusion-weighted MR imaging may be useful in assessing clival tumors, particularly in differentiating chordoma from chondrosarcoma. A prospective study of a larger cohort will be required to determine the value of ADC in predicting histopathologic diagnosis.

    View details for DOI 10.3174/ajnr.A3333

    View details for PubMedID 23124635

  • Using bioabsorbable fixation systems in the treatment of pediatric skull deformities leads to good outcomes and low morbidity CHILDS NERVOUS SYSTEM Gephart, M. G., Woodard, J. I., Arrigo, R. T., Lorenz, H. P., Schendel, S. A., Edwards, M. S., Guzman, R. 2013; 29 (2): 297-301

    Abstract

    Bioabsorbable fixation systems have been widely employed in pediatric patients for cranial reconstruction, obviating the complications of hardware migration and imaging artifact occurring with metallic implants. Recent concern over complications unique to bioabsorbable materials, such as inflammatory reaction and incomplete resorption, necessitates additional conclusive studies to further validate their use in pediatric neurosurgery and craniofacial surgery. Likewise, long-term follow-up in this clinical cohort has not previously been described.We included consecutive pediatric patients under the age of 2, from Lucile Packard Children's Hospital, who underwent cranial vault reconstruction with the use of a bioabsorbable fixation system between 2003 and 2010. Hospital records were queried for patient characteristics, intraoperative data, and postoperative complications.Ninety-five patients with the following preoperative pathologies were analyzed: craniosynostosis (87), cloverleaf skull (5), frontonasal dysplasia (1), and frontonasal encephalocele (2). Median age was 6 months (range 1-24 months). Average case duration was 204 minutes (range 40-392 min), with median of 154 mL blood loss (range 30-500 mL). Ninety-three percent of patients had 1-4 plates implanted with 48% receiving three plates. The median number of screws used was 59 (range 0-130). The median length of hospital stay was 4 days (range 2-127 days) with an average follow-up of 22 months (five postoperative visits). The complications related to hardware implantation included swelling (1%) and broken hardware (1%), the latter of which required reoperation.The bioabsorbable fixation systems for cranial vault reconstruction in children less than 2 years of age is safe with tolerable morbidity rates.

    View details for DOI 10.1007/s00381-012-1938-y

    View details for Web of Science ID 000314028100019

    View details for PubMedID 23099613

  • Extravascular Papillary Endothelial Hyperplasia Mimicking Neoplasm After Radiosurgery: Case Report NEUROSURGERY Karamchandani, J., Vogel, H., Fischbein, N., Gibbs, I., Edwards, M. S., Harsh, G. 2012; 70 (4): E1043-E1048

    Abstract

    Papillary endothelial hyperplasia (PEH) is a rare form of exuberant reactive endothelial proliferation that can mimic neoplasm. We report the largest series of patients with histologically confirmed intracranial extravascular PEH developing in the field of previous treatment with stereotactic radiosurgery.We collected the clinical, radiological, surgical, and pathological findings from 4 patients in whom intracranial extravascular PEH developed after treatment with stereotactic radiosurgery. In all patients, the development of an enlarging hemorrhagic mass lesion at the site of previous radiotherapy on magnetic resonance imaging was radiographically suspicious for neoplasm and prompted biopsy or resection. All 4 patients elected to undergo biopsy or surgical resection. Histological examination of the biopsy and resection specimens in all patients demonstrated the classic features of PEH.The interval to the development of PEH ranged from 5 months to 6 years, 10 months. Clinical follow-up was available for 3 of the 4 patients. None of these 3 patients have demonstrated evidence of recurrence during a mean follow-up period of 22 months (range, 15-30 months). These patients share common radiological features, potentially allowing preoperative diagnosis and improved guidance of clinical management. These cases suggest a link between radiosurgery and the development of PEH. These findings also suggest that PEH should be considered in the differential diagnosis for patients treated with radiosurgery in whom a hemorrhagic mass lesion subsequently develops at or near the site of previous treatment. We think that complete surgical excision is the best treatment for intracranial PEH.

    View details for DOI 10.1227/NEU.0b013e31822e81f9

    View details for Web of Science ID 000301934000010

    View details for PubMedID 22426048

  • Ventricular Access Devices Are Safe and Effective in the Treatment of Posthemorrhagic Ventricular Dilatation prior to Shunt Placement PEDIATRIC NEUROSURGERY Tian, A. G., Hintz, S. R., Cohen, R. S., Edwards, M. S. 2012; 48 (1): 13-20

    Abstract

    Intraventricular hemorrhage of prematurity (IVH) is a diagnosis that has become more frequent in recent years. Advances in medical care have led to survival of increasingly premature infants, as well as infants with more complex medical conditions. Treatment with a ventricular access device (VAD) was reported almost 3 decades ago; however, it is unclear how effective this treatment is in the current population of premature infants. At our institution (from 2004 to present), we treat posthemorrhagic hydrocephalus (PHH) with a VAD. In order to look at safety and efficacy, we retrospectively combed the medical records of premature children, admitted to Lucile Packard Children's Hospital from January 2005 to December 2009, and identified 310 premature children with IVH. Of these, 28 children required treatment for PHH with a VAD. There were no infections associated with placement of these devices and a very low rate of other complications, such as need for repositioning (7.41%) or replacement (3.75%). Our data show that treatment with a VAD is very safe, with few complications and can be used to treat PHH in this very complex infant population.

    View details for DOI 10.1159/000337876

    View details for Web of Science ID 000309885700003

    View details for PubMedID 22832699

  • Management of Pediatric Intracranial Arteriovenous Malformations: Experience With Multimodality Therapy NEUROSURGERY Darsaut, T. E., Guzman, R., Marcellus, M. L., Edwards, M. S., Tian, L., Do, H. M., Chang, S. D., Levy, R. P., Adler, J. R., Marks, M. P., Steinberg, G. K. 2011; 69 (3): 540-556

    Abstract

    Successful management of pediatric arteriovenous malformations (AVMs) often requires a balanced application of embolization, surgery, and radiosurgery.To describe our experience treating pediatric AVMs.We analyzed 120 pediatric patients (< 18 years of age) with AVMs treated with various combinations of radiosurgery, surgery, and endovascular techniques.Between 1985 and 2009, 76 children with low Spetzler-Martin grade (1-3) and 44 with high-grade (4-5) AVMs were treated. Annual risk of hemorrhage from presentation to initial treatment was 4.0%, decreasing to 3.2% after treatment initiation until confirmed obliteration. Results for AVM obliteration were available in 101 patients. Initial single-modality therapy led to AVM obliteration in 51 of 67 low-grade (76%) and 3 of 34 high-grade (9%) AVMs, improving to 58 of 67 (87%) and 9 of 34 (26%), respectively, with further treatment. Mean time to obliteration was 1.8 years for low-grade and 6.4 years for high-grade AVMs. Disabling neurological complications occurred in 4 of 77 low-grade (5%) and 12 of 43 high-grade (28%) AVMs. At the final clinical follow-up (mean, 9.2 years), 48 of 67 patients (72%) with low-grade lesions had a modified Rankin Scale score (mRS) of 0 to 1 compared with 12 of 34 patients (35%) with high-grade AVMs. On multivariate analysis, significant risk factors for poor final clinical outcome (mRS ? 2) included baseline mRS ? 2 (odds ratio, 9.51; 95% confidence interval, 3.31-27.37; P < .01), left-sided location (odds ratio, 3.03; 95% confidence interval, 1.11-8.33; P = .03), and high AVM grade (odds ratio, 4.35; 95% confidence interval, 1.28-14.28; P = .02).Treatment of pediatric AVMs with multimodality therapy can substantially improve obliteration rates and may decrease AVM hemorrhage rates. The poor natural history and risks of intervention must be carefully considered when deciding to treat high-grade pediatric AVMs.

    View details for DOI 10.1227/NEU.0b013e3182181c00

    View details for Web of Science ID 000293586200005

    View details for PubMedID 21430584

  • Liposomal cytarabine for central nervous system embryonal tumors in children and young adults JOURNAL OF NEURO-ONCOLOGY Partap, S., Murphy, P. A., Vogel, H., Barnes, P. D., Edwards, M. S., Fisher, P. G. 2011; 103 (3): 561-566

    Abstract

    To assess the tolerability and efficacy of liposomal cytarabine (LC), an encapsulated, sustained-release, intrathecal (IT) formulation of cytosine arabinoside, in de novo and relapsed central nervous system (CNS) embryonal tumors in children and young adults. We studied retrospectively all patients less than age 30 at our institution treated consecutively with LC for medulloblastoma (MB), primitive neuroectodermal tumor (PNET), and atypical teratoid rhabdoid tumor (ATRT). Seventeen patients received LC (2 mg/kg up to 50 mg, every 2 weeks to monthly) at diagnosis of high-risk CNS embryonal tumor (2 PNET, 3 ATRT) or relapse of MB (12 MB; 9 had leptomeningeal metastases). Sixteen patients received concurrent systemic chemotherapy. A total of 108 doses were administered (IT 82, intraventricular 26) with a mean of six (range 1-16) treatments per patient. Only three administrations were associated with adverse effects of arachnoiditis or headache. None developed malignant cerebrospinal fluid (CSF) cytology while receiving LC. All the six evaluable patients with malignant CSF cytology and treated with at least two doses cleared their CSF (mean 3 doses, range 1-5). Median overall survival in relapse patients was 9.1 months. Five patients (4 de novo and 1 relapsed) remain alive in complete remission for a median 26.8 months from first LC. Liposomal cytarabine is an easily administered, well-tolerated, and active drug in patients with high-risk embryonal neoplasms. One-third of our cohort remains in remission from otherwise fatal diagnoses. Our findings warrant a phase II trial of LC in newly diagnosed or recurrent CNS embryonal tumors.

    View details for DOI 10.1007/s11060-010-0419-y

    View details for Web of Science ID 000291703000018

    View details for PubMedID 20859651

  • Perioperative posterior reversible encephalopathy syndrome in 2 pediatric neurosurgery patients with brainstem ependymoma Report of 2 cases JOURNAL OF NEUROSURGERY-PEDIATRICS Gephart, M. G., Taft, B. P., Giese, A., Guzman, R., Edwards, M. S. 2011; 7 (3): 235-237

    Abstract

    Posterior reversible encephalopathy syndrome (PRES) has been described in pediatric neurooncology patients, although it has not been documented perioperatively in pediatric neurosurgery patients not actively receiving chemotherapy. Recently at the authors' facility, 2 cases of PRES were diagnosed perioperatively in children with brainstem ependymoma. Both patients had presented with hypertension, altered mental status, and seizures and demonstrated MR imaging features consistent with PRES. The patients were treated with antiseizure and antihypertension medications, leading to improvement in both clinical symptoms and neuroimaging findings. These cases are the first to document PRES in perioperative pediatric neurosurgery patients not actively receiving chemotherapy. Both patients had ependymoma involving the brainstem, which may have led to intra- and perioperative hemodynamic instability (including hypertension) and predisposed them to this syndrome. An awareness of PRES in similar scenarios will aid in the prevention, diagnosis, and treatment of pediatric neurosurgery patients with this syndrome.

    View details for DOI 10.3171/2010.12.PEDS10299

    View details for Web of Science ID 000287676800005

    View details for PubMedID 21361759

  • Extravascular Papillary Endothelial Hyperplasia Mimicking Neoplasm Following Radiosurgery. Neurosurgery Karamchandani, J., Vogel, H., Fischbein, N., Gibbs, I., Edwards, M. S., Harsh, G. 2011

    Abstract

    BACKGROUND AND IMPORTANCE:: Papillary endothelial hyperplasia (PEH) is a rare form of exuberant reactive endothelial proliferation that can mimic neoplasm. We report the largest series of patients with histologically confirmed intracranial extravascular PEH developing in the field of prior treatment with stereotactic radiosurgery. CLINICAL PRESENTATION:: We collected the clinical, radiological, surgical, and pathologic findings in four cases of patients who developed intracranial extravascular PEH following treatment with stereotactic radiosurgery. In all cases the development of an enlarging hemorrhagic mass lesion in the site of prior radiotherapy on MRI was radiographically suspicious for neoplasm and prompted biopsy or resection. In all four cases the patients elected to undergo biopsy or surgical resection. Histologic examination of the biopsy and resection specimens in all cases demonstrated the classic features of PEH. CONCLUSION:: The interval to the development of PEH ranged from five months to six years and ten months. Clinical follow up was available for three of the four patients. None of these three patients has demonstrated evidence of recurrence during a mean follow-up period of 22 months (15-30 months). These cases share common radiological features, potentially allowing for pre-operative diagnosis and improved guidance of clinical management. These cases suggest a link between radiosurgery and the development of PEH. These findings also suggest that PEH should be considered in the differential diagnosis for patients treated with radiosurgery who subsequently develop a hemorrhagic mass lesion at or near the site of prior treatment. We think that complete surgical excision is the best treatment for intracranial PEH.

    View details for PubMedID 21937944

  • Loss of SMARCB1/INI1 expression in poorly differentiated chordomas ACTA NEUROPATHOLOGICA Mobley, B. C., McKenney, J. K., Bangs, C. D., Callahan, K., Yeom, K. W., Schneppenheim, R., Hayden, M. G., Cherry, A. M., Gokden, M., Edwards, M. S., Fisher, P. G., Vogel, H. 2010; 120 (6): 745-753

    Abstract

    Chordomas are malignant neoplasms that typically arise in the axial spine and primarily affect adults. When chordomas arise in pediatric patients they are more likely to display unusual histological features and aggressive behavior. We noted the absence of SMARCB1/INI1 expression by immunohistochemistry in an index case of poorly differentiated chordoma of the sacrum, leading us to further examine SMARCB1/INI1 expression as well as that of brachyury, a highly specific marker of notochordal differentiation, in 3 additional poorly differentiated chordomas of the clivus, 10 typical chordomas, and 8 atypical teratoid/rhabdoid tumors (AT/RTs). All 4 poorly differentiated chordomas and all AT/RTs lacked nuclear expression of SMARCB1/INI1, while the 10 typical chordomas maintained strong nuclear SMARCB1/INI1 immunoreactivity. All 10 typical and 4 poorly differentiated chordomas expressed brachyury; all 8 AT/RTs were brachyury immunonegative. Cytogenetic evaluation utilizing FISH probes near the SMARCB1/INI1 locus on chromosome 22q was also performed in all of the poorly differentiated chordomas in this series. Three of the four poorly differentiated chordomas had evidence for deletion of this region by FISH. Analysis of the SMARCB1/INI1 gene sequence was performed using formalin-fixed paraffin-embedded tissue in all cases and no point mutations were observed. In summary, all poorly differentiated chordomas in this series showed the absence of SMARCB1/INI1 expression, and were reliably distinguished from AT/RTs, clinically by their characteristic primary sites of origin and pathologically by strong nuclear brachyury expression. Our findings reveal a likely role for SMARCB1/INI1 in a subset of chordomas with aggressive features.

    View details for DOI 10.1007/s00401-010-0767-x

    View details for Web of Science ID 000284593200005

    View details for PubMedID 21057957

  • Langerhans cell histiocytosis in a 5-month-old presenting with biparietal masses Case report JOURNAL OF NEUROSURGERY-PEDIATRICS Pricola, K. L., Karamchandani, J., Vogel, H., Dahl, G. V., Yeom, K. W., Edwards, M. S., Guzman, R. 2010; 6 (4): 393-397

    Abstract

    Langerhans cell histiocytosis (LCH) is a rare proliferative disorder that occurs most commonly in the pediatric population as a result of pathological clonal proliferation of Langerhans cells with subsequent damage and destruction to surrounding tissue. Clinically, LCH presents in a variety of ways, which often results in prolonged time to diagnosis and subsequently poorer outcomes. In this case report, the authors describe an unusually early presentation of multisystem LCH in a patient at birth, which resulted in a 5-month delay to diagnosis and treatment. This patient presented both atypically young and with an uncommon initial manifestation of multisystem disease with multiple soft-tissue swellings rather than early skin involvement. Additionally, this patient had an unusual radiographic appearance with biparietal skull destruction on initial skull radiographs and biparietal soft-tissue lesions on CT resembling cephalohematoma at 3 months of age. The clinical and radiological evaluation, pathology, and treatment strategies are discussed, with particular attention paid to the importance of further workup of atypical nonresolving cephalohematomas to prevent disease progression and poorer outcomes.

    View details for DOI 10.3171/2010.7.PEDS10149

    View details for Web of Science ID 000282244400020

    View details for PubMedID 20887116

  • Pineal Parenchymal Tumor of Intermediate Differentiation: Clinicopathological Report and Analysis of Epidermal Growth Factor Receptor Variant III Expression NEUROSURGERY Li, G., Mitra, S., Karamchandani, J., Edwards, M. S., Wong, A. J. 2010; 66 (5): 963-968

    Abstract

    Epidermal growth factor receptor (EGF) receptor gene amplification is commonly seen in cancer and is the target of many therapies. EGF receptor variant III (EGFRvIII) is the most common variant of the EGF receptor and has been detected in a large percentage of patients with glioblastoma multiforme but not in normal brain. Therapies targeting EGFRvIII are currently being investigated in clinical and preclinical trials.A 14-year-old girl who presented with headaches was found to have a pineal parenchymal tumor of intermediate differentiation. We review the histopathological properties that led to the diagnosis of this tumor. EGF receptor gene amplification and EGFRvIII expression have not been analyzed in pineal tumors. We investigated EGF receptor gene status and EGFRvIII expression in this patient's tumor.Tumor tissue was obtained and analyzed with flow cytometry, reverse-transcriptase polymerase chain reaction, and Western blot analysis. EGFRvIII was detected by all 3 methods. The tumor was further analyzed by fluorescence in situ hybridization, which did not reveal EGF receptor gene amplification.This is the first report of EGFRvIII expression in a pineal tumor. It is interesting that this variant is detected in the absence of EGF receptor gene amplification. A larger study evaluating the presence of EGFRvIII in pineal tumors is needed.

    View details for DOI 10.1227/01.NEU.0000367726.49003.F1

    View details for Web of Science ID 000276970800026

    View details for PubMedID 20404701

  • Intramedullary papillary ependymoma with choroid plexus differentiation and cerebrospinal fluid dissemination to the brain Case report JOURNAL OF NEUROSURGERY-PEDIATRICS Dulai, M. S., Caccamo, D. V., Briley, A. L., Edwards, M. S., Fisher, P. C., Lehman, N. L. 2010; 5 (5): 511-517

    Abstract

    This 8-year-old girl presented with a papillary ependymoma in the thoracic spinal cord. Resection was followed by recurrence at the primary site and later in the lumbosacral thecal sac, followed by cerebrospinal fluid dissemination to the brain approximately 5 years after her initial presentation. The tumor showed cytological and immunohistochemical features overlapping those of classic ependymomas and choroid plexus tumors similar to those seen in uncommon supratentorial papillary ependymomas, also known as papillary tumors of the pineal region. The histopathological and clinical courses of this rare spinal papillary ependymoma exhibiting mixed ependymal and choroid plexus-like differentiation are discussed.

    View details for DOI 10.3171/2009.12.PEDS09130

    View details for Web of Science ID 000277131500016

    View details for PubMedID 20433266

  • Intraventricular metaplastic meningioma in a child: case report and review of the literature NEUROPATHOLOGY Dulai, M. S., Khan, A., Edwards, M. S., Vogel, H. 2009; 29 (6): 708-712

    Abstract

    Childhood meningiomas are rare and display important differences from adult forms. We report the first case of an intraventricular metaplastic meningioma arising in a child. A 7-year-old female underwent resection of an enhancing tumor arising within the left lateral ventricle. It was composed of monomorphic cells embedded within an abundant myxoid stroma. The cells demonstrated epithelial membrane antigen and vimentin immunoreactivity. Ultrastructural analysis demonstrated intermediate filaments, complex intercellular interdigitations and desmosomes, and a diagnosis of myxoid (metaplastic) meningioma was rendered. This case reflects the higher incidence of intraventricular meningiomas in childhood and greater incidence of intraventricular meningiomas in the left lateral ventricle. Recognition of the grade I myxoid meningioma in this case is paramount since chordoid meningiomas, which share similar histologic features, are of a higher grade and worse prognosis.

    View details for DOI 10.1111/j.1440-1789.2009.01008.x

    View details for Web of Science ID 000271713800010

    View details for PubMedID 19389075

  • Vein of Galen malformation NEUROSURGICAL FOCUS Hoang, S., Choudhri, O., Edwards, M., Guzman, R. 2009; 27 (5)

    Abstract

    A vein of Galen malformation is a rare intracranial vascular lesion affecting the pediatric population. Its poor prognosis has been significantly improved with the development of endovascular embolization. In this paper the authors review the developmental mechanisms, clinical pathophysiology, and the available data on the management and outcome of the disease.

    View details for DOI 10.3171/2009.8.FOCUS09168

    View details for Web of Science ID 000271373800008

    View details for PubMedID 19877798

  • Successful treatment of severe cerebral vasospasm following hemorrhage of an arteriovenous malformation JOURNAL OF NEUROSURGERY-PEDIATRICS Pendharkar, A. V., Guzman, R., Dodd, R., Cornfield, D., Edwards, M. S. 2009; 4 (3): 266-269

    Abstract

    The authors describe the case of a 13-year-old boy who presented with an intraventricular hemorrhage caused by a left trigonal arteriovenous malformation. After an initial recovery, the patient experienced complete right-sided paresis on posthemorrhage Day 6. Severe cerebral vasospasm was found on MR angiography and confirmed on conventional cerebral angiography. Intraarterial nicardipine injection and balloon angioplasty were successfully performed with improved vasospasm and subsequent neurological recovery. Cerebral vasospasm should be considered in the differential diagnosis for neurological deterioration following an arteriovenous malformation hemorrhage, and aggressive treatment can be administered to prevent ischemia and further neurological deficits.

    View details for DOI 10.3171/2009.4.PEDS09126

    View details for Web of Science ID 000269223300012

    View details for PubMedID 19772412

  • Papillary Tumor of the Spinal Cord Report of 2 Cases AMERICAN JOURNAL OF SURGICAL PATHOLOGY Mobley, B., Kalani, M. S., Harsh, G. R., Edwards, M. S., Vogel, H. 2009; 33 (8): 1191-1197

    Abstract

    Intramedullary spinal cord tumors constitute a small fraction of central nervous system tumors in the pediatric population; of these, the majority are ependymomas or astrocytomas. We report 2 pediatric spinal cord tumor cases with unique morphologic and immunohistochemical features. The first patient presented at age 7 with an intramedullary tumor of the thoracic spine. She suffered lumbar, cerebellar, and temporal lobe recurrences despite surgical resection and radiation. The second patient presented at age 17 with an intramedullary tumor of the cervical spine. The tumor recurred locally and in the cerebellum. Magnetic resonance imaging studies demonstrated gadolinium enhancement in each case. Microscopy showed papillary and solid cytoarchitecture with monomorphous epithelioid cells arranged around vascular papillae. Immunohistochemistry in each case revealed diffuse epithelial membrane antigen, cytokeratin, and E-cadherin reactivity. Glial fibrillary acidic protein staining was focal in case 1 and completely negative in case 2. Neural cell adhesion molecule showed patchy membranous reactivity and synaptophysin was negative. Electron microscopy showed ependymal differentiation. The clinical features, including propensity for recurrence and remote subarachnoid spread, and the pathologic features of these tumors are reminiscent of papillary tumor of the pineal region, ependymoma, and choroid plexus papilloma. The cases presented may constitute a new neoplastic entity within the recently described spectrum of central nervous system tumors with ependymal features.

    View details for Web of Science ID 000268850300010

    View details for PubMedID 19417584

  • Recurring osteoma within a calcium phosphate bone cement cranioplasty: case report. Neurosurgery Hayden, M. G., Guzman, R., Dulai, M. S., Mobley, B. C., Edwards, M. S. 2009; 64 (4): E775-6

    Abstract

    We present a unique case of a recurrent osteoma within a cranioplasty performed with calcium phosphate bone cement.The patient is a 7-year-old boy who had initially undergone a craniotomy for resection of a frontal cranial tumor followed by a cranioplasty with artificial bone matrix. On routine follow-up evaluation 2 years later, the patient had a mass expanding from the cranioplasty.At the time of reoperation, the patient was found to have a histopathologically confirmed recurrent osteoma within the artificial bone matrix. The patient later underwent repair of the frontal cranial defect using a patient-specific implant.We discuss this unusual case, treatment, and possible causes. We believe that a safety margin and curettage of the resection border as well as resection of the overlying periosteum might prevent recurrence.

    View details for DOI 10.1227/01.NEU.0000339126.47870.43

    View details for PubMedID 19349808

  • Tethered cord syndrome: nationwide inpatient complications and outcomes. Neurosurgical focus Lad, S. P., Patil, C. G., Ho, C., Edwards, M. S., Boakye, M. 2007; 23 (2): E3-?

    Abstract

    Previous investigations of health outcome after spinal surgery for tethered cord syndrome (TCS) have been single-institution studies. The aim of this study was to report inpatient complications and outcomes on a nationwide level.The Nationwide Inpatient Sample (NIS) was used to identify patients who underwent spinal surgery for TCS in the US between 1993 and 2002. Patients who had a primary diagnosis of TCS (ICD-9 742.59) and also underwent spinal laminectomies were included in this study. Multivariate analysis was performed to analyze the effects of patient and hospital characteristics on variables such as mortality rate, nonfatal complications, LOS, and adverse outcomes in general (defined as death or discharge to an institution rather than home).The NIS sample included data on 9733 patients with TCS who underwent surgery. The means for mortality rate, complication rate, and LOS, respectively, were 0.0005%, 9.48%, and 5.6 days. Postoperative hemorrhages or hematomas (mean rate 2.3%) were the most common complications reported. Age and complications were the only significant predictors of adverse outcome on multivariate analysis. Patients older than 65 years had a threefold increase in risk of adverse outcome compared with patients 18 to 44 years of age. On average, one postoperative complication led to a 3-day increase in mean LOS and added more than $9000 to hospital charges.This study provides a national perspective on inpatient complications and outcomes after spinal surgery for TCS in the United States. The authors have demonstrated the impact of age, complications, and medical comorbidities on the outcome of surgery for patients with this common disorder.

    View details for PubMedID 17961009

  • Multiple aneurysms in childhood JOURNAL OF VASCULAR SURGERY English, W. P., Edwards, M. S., Pearce, J. D., Mondi, M. M., Hundley, J. C., Hansen, K. J. 2004; 39 (1): 254-259

    Abstract

    Arterial aneurysms in children are rare. When present, they are often associated with connective tissue disorders or arteritidies. Idiopathic aneurysms occurring at multiple sites throughout the arterial tree are rare, with only ten cases reported. This report describes a case of multiple arterial aneurysms of uncertain origin involving upper-extremity, extracranial cerebrovascular, aortoiliac, and renal arteries in a 14-year-old boy. The clinical presentation, vascular reconstruction, pathologic findings, and a brief review of the literature are described.

    View details for DOI 10.1016/j.jvs.2003.07.019

    View details for Web of Science ID 000187840600051

    View details for PubMedID 14718849

  • Hyperfractionated craniospinal radiation therapy for primitive neuroectodermal tumors: Results of a phase II study INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Prados, M. D., Edwards, M. S., Chang, S. M., Russo, C., Davis, R., Rabbitt, J., Page, M., Lamborn, K., Wara, W. M. 1999; 43 (2): 279-285

    Abstract

    To report the results of a Phase II study of hyperfractionated craniospinal radiation therapy, with and without adjuvant chemotherapy for primitive neuroectodermal brain tumors (PNETs) and malignant ependymomas.Newly diagnosed PNET or malignant ependymomas were treated with hyperfractionated craniospinal radiation therapy. The primary tumor site was treated to a dose of 72 Gy, with 30 Gy given to the rest of the craniospinal axis. The fraction size was 1.0 Gy, given twice a day. Patients with poor risk factors also received adjuvant chemotherapy with CCNU, cisplatin, and vincristine. Patients had follow-up for survival, time to tumor progression, and patterns of relapse.A total of 39 patients (21 males/18 females) were treated between March 12, 1990 and October 29, 1992. The median age was 16 years (range 3-59 years). Tumor types included 25 medulloblastomas, 5 pineoblastomas, 5 cerebral PNETs, 1 spinal cord PNET, and 3 malignant ependymomas. Twenty cases were staged as poor-risk and received adjuvant chemotherapy following radiation. Three-year progression-free survival (PFS) was 60% and 63% for poor-risk and good-risk patients, respectively. Overall 3-year survival for these groups was 70% and 79%, respectively. For the 25 patients with medulloblastoma, there were 16 good-risk and 9 poor-risk patients. Three-year PFSs were 63% and 56%, respectively. The 5-year survival for good-risk medulloblastoma was 69% with 43.7% of these patients having failures outside the primary site.Survival in patients with good-risk medulloblastoma was no better than that seen in previous studies with single-fraction radiation, and the rate of failure outside the primary site is excessive. Those with poor-risk features had comparable survival to that seen in patients with good risk factors, but these patients were treated with chemotherapy, and the role that hyperfractionated radiation played in their outcome is uncertain.

    View details for Web of Science ID 000078564800005

    View details for PubMedID 10030250

  • Long-term benefits of early neurosurgery for lipomyelomeningocele JOURNAL OF UROLOGY Wu, H. Y., Kogan, B. A., Baskin, L. S., Edwards, M. S. 1998; 160 (2): 511-514

    Abstract

    Our previous experience with early neurosurgery for lipomyelomeningocele revealed that patients undergoing repair before age 1.5 years were more likely to have normal bladder function. We evaluate the durability of the urological benefits in patients with lipomyelomeningocele with longer followup.A retrospective chart review was performed on all patients who underwent urodynamic testing before and after primary neurosurgical repair of lipomyelomeningocele. A total of 43 patients presented between 1983 and 1995 with at least 12 months of followup (median 68, range 15 to 167).Of the 43 patients 36 (84%) maintained stable clinical and urodynamic function, and 7 (16%) had late deterioration, which occurred between 9 months and 8 years postoperatively. Of 19 patients with normal urodynamic studies preoperatively 14 (74%) maintained normal function. Overall, 14 of 43 patients (33%) with lipomyelomeningocele had normal bladder and sphincter function during followup. The principal predictor of long-term normal bladder function was preoperative urodynamic status, since urodynamic studies were preoperatively normal in 13 of 14 patients (93%) who maintained normal bladder and sphincter function. Late neurosurgery was equally efficacious if urodynamic studies were normal.Our data continue to support early diagnosis and neurosurgical intervention in patients with lipomyelomeningocele, since there is a higher likelihood of normal preoperative function that can be preserved. Furthermore, the results are durable in 84% of cases. However, close followup is necessary, since deterioration can occur up to 8 years postoperatively.

    View details for Web of Science ID 000074928200075

    View details for PubMedID 9679919

  • Endovascular treatment of mural-type vein of Galen malformations JOURNAL OF NEUROSURGERY Von Halbach, V., Dowd, C. F., Higashida, R. T., Balousek, P. A., Ciricillo, S. F., Edwards, M. S. 1998; 89 (1): 74-80

    Abstract

    In this study the authors report on the results of endovascular treatment for mural-type vein of Galen malformations (VGMs) in a group of infants.Eight children (six infants and two neonates) who suffered from symptoms caused by a mural-type VGM were treated by means of endovascular therapy. Their age at the time of treatment ranged from 13 days to 19 months (mean 7.6 months). Two neonates and three infants who presented with hydrocephalus and increased head circumference, one of whom was stabilized with a shunt, underwent elective closure of the malformations 3, 4, 6, 6, and 13 months later, respectively. Two patients presented with hemorrhage; one had an intraventricular hemorrhage (IVH) on the 1st day of life and one, a 5-month-old infant, suffered a large parenchymal hemorrhage and an IVH; both patients were immediately cured by means of endovascular techniques. One child presented with a seizure and cortical venous drainage that were treated immediately. Eleven separate treatment sessions were conducted; eight via transarterial femoral access and the remaining three via a transvenous approach. Two patients were treated by using transfemoral transvenous embolization with fibered coils, and one patient required a transtorcular transvenous approach to permit complete closure of the fistula with electrolytically detachable coils. The embolic devices used included silk suture emboli (three patients), electrolytically detachable coils (three patients), and fibered platinum coils (seven patients). In seven patients, complete closure was demonstrated on postembolization arteriographic studies. The eighth patient had stagnant flow in a giant 6-cm varix treated with arterial and venous coils but has not yet undergone follow-up studies. Late follow-up arteriography was performed in four patients at times ranging from 11 to 24 months postprocedure. In one patient, thrombosis of the malformation and shrinkage of the varix were confirmed on follow-up computerized tomography scanning. The remaining three patients have not yet undergone follow-up angiographic examination. Two asymptomatic complications occurred, including separation of the distal catheter, which was removed with a snare device, and a single platinum coil that embolized to the lung, producing no symptoms in 101 months of clinical follow up. The follow-up period ranged from 3 to 105 months, with a mean of 52 months.Endovascular therapy is the treatment of choice for mural-type VGMs and offers a high rate of cure with low morbidity.

    View details for Web of Science ID 000074325600011

    View details for PubMedID 9647175

  • Influence of a child's sex on medulloblastoma outcome JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Weil, M. D., Lamborn, K., Edwards, M. S., Wara, W. M. 1998; 279 (18): 1474-1476

    Abstract

    Aggressive treatment of medulloblastoma, the most common pediatric brain tumor, has not improved survival. Identifying better prognostic indicators may warrant less morbid therapy.To investigate the role of sex on outcome of medulloblastoma.Retrospective study of significant factors for survival with a median follow-up of 82 months.University medical center.A total of 109 consecutive, pediatric patients treated for primary medulloblastoma from 1970 to 1995 with surgery and postoperative radiotherapy and, after 1979, chemotherapy.Factors independently associated with survival.The final multivariate model predicting improved survival included sex (hazard ratio, 0.52; 95% confidence interval [CI], 0.29-0.92; P=.03; favoring female), metastases at presentation (hazard ratio, 2.01; 95% CI, 1.14-3.52; P=.02), and extent of surgical resection (hazard ratio, 0.60; 95% CI, 0.34-1.04; P=.07; favoring greater resection). The overall, 5-year freedom from progression was 40% and survival was 49%. Radiotherapy dose (P=.72), and chemotherapy (P=.90) did not significantly affect a disease outcome.The sex of the child was an important predictor for survival of medulloblastoma; girls had a much better outcome. The difference in survival between sexes should be evaluated in prospective, clinical trials.

    View details for Web of Science ID 000073463500038

    View details for PubMedID 9600483

  • Endoscopic third ventriculocisternostomy: MR assessment of patency with 2-D cine phase-contrast versus T2-weighted fast spin echo technique PEDIATRIC NEUROSURGERY Fischbein, N. J., Ciricillo, S. F., Barr, R. M., McDermott, M., Edwards, M. S., Geary, S., Barkovich, A. J. 1998; 28 (2): 70-78

    Abstract

    To determine if fast spin-echo T2 (FSE) is of equal value to flow-sensitive 2D cine phase-contrast (CPC) to assess patency of endoscopic third ventriculocisternostomies (VC).We reviewed clinical charts and MR scans of 27 patients who underwent third VC for treatment of obstructive hydrocephalus. Thirty-nine postoperative scans included both sequences and were assessed for the presence or absence of flow-related signal changes.In 28 cases, FSE, CPC, and clinical findings suggested patency. In 1 case, CPC and FSE suggested occlusion, which was confirmed clinically and operatively. In the remaining cases, FSE showed better clinical correlation than did CPC.The assessment of third VC patency with FSE, a sequence available on most clinical scanners without a requirement for special hardware and software, is at least as sensitive in the qualitative assessment of VC function as CPC.

    View details for Web of Science ID 000075076300004

    View details for PubMedID 9693335

  • Adult medulloblastoma: An analysis of survival and prognostic factors CANCER JOURNAL Le, Q. T., Weil, M. D., Wara, W. M., Lamborn, K. R., Prados, M. D., Edwards, M. S., Gutin, P. H. 1997; 3 (4): 238-245

    Abstract

    This analysis aimed to review the experience in the management of adult medulloblastoma at the University of California, San Francisco, and to identify important prognostic factors for survival and posterior fossa control.We performed a retrospective review of 34 adult patients, age > or = 15, with cerebellar medulloblastoma treated with radiotherapy at the University of California, San Francisco from 1970 to 1994. All patients underwent a surgical procedure (complete resection in 17, subtotal resection in 10, and biopsy alone in seven), followed by craniospinal irradiation. Most patients treated after 1979 also received chemotherapy. Twenty were classified as poor-risk due to either incomplete resection or evidence of disease outside of the posterior fossa at diagnosis.The 5-year posterior fossa control and overall survival rates were 61% and 58%, respectively. The majority of relapses occurred in the posterior fossa (14 of 17). Multivariate analysis revealed that age (favoring older patients), gender (favoring female patients), and extent of disease at diagnosis (favoring localized disease) were important prognostic factors for posterior fossa control. There was a trend toward improved posterior fossa control with higher radiation dose to the posterior fossa in patients with a complete resection. Gender and extent of disease at presentation were significant prognostic factors for survival. The 5-year survival rates were 92% for female patients versus 40% for male patients, and 67% for patients with localized disease versus 25% for those with disseminated disease. The prognosis following recurrence was poor; all died of the disease.Survival for adult medulloblastoma was comparable to its pediatric counterpart. In patients with localized disease at presentation, gender (favoring female patients) and age (favoring older patients) were important prognostic factors for posterior fossa control and survival. In patients with disseminated disease at presentation, the prognosis is poor, and innovative therapy is needed to improve survival.

    View details for Web of Science ID A1997XN19200009

    View details for PubMedID 9263630

  • Idiopathic hypothalamic diabetes insipidus, pituitary stalk thickening, and the occult intracranial germinoma in children and adolescents JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Mootha, S. L., Barkovich, A. J., Grumbach, M. M., Edwards, M. S., Gitelman, S. E., Kaplan, S. L., Conte, F. A. 1997; 82 (5): 1362-1367

    Abstract

    We report nine consecutive children and adolescents [five females and four males; aged 2 yr 8 months (m) to 18 yr 1 m] studied over the last 5 yr with idiopathic central diabetes insipidus. In addition to vasopressin deficiency, anterior pituitary hormone deficiencies were detected, either on evaluation at presentation or during follow-up studies over the following 3 yr. Four patients had an increased concentration of plasma PRL. One patient had multiple pituitary hormone deficiencies at diagnosis, and two others developed the same by 21 m of follow-up. Brain magnestic resonance imaging scans, performed at presentation, were originally interpreted as normal in four of nine patients, except for absence of the bright posterior pituitary signal; after retrospective review, two of nine were considered normal. All of the brain magnetic resonance imaging (MRI) scans showed positive findings by 14 m of follow-up. The first abnormal finding in all patients was isolated pituitary stalk thickening. Evaluation of cerebrospinal fluid (CSF) for hCG was positive in three of eight evaluated patients; the three positive CSF values were found at presentation and 3 and 9 m after presentation. All eight patients assessed were negative for CSF alpha-fetoprotein and cytology, and no patient had serum tumor markers. Transsphenoidal biopsy of the lesion in seven of nine patients showed a germinoma in six patients and inflammatory cells in one. The six patients with documented germinoma comprise 31% of the intracranial germinomas diagnosed in this age group at the University of California-San Francisco during the last 5 yr. The patient with mononuclear inflammatory cells on biopsy along with one other patient have had spontaneous resolution of their stalk thickening. So-called "idiopathic" central diabetes insipidus warrants close follow-up to determine the etiology, especially if anterior pituitary hormone deficiencies are detected. Normal brain MRI scans or scans that show isolated pituitary stalk thickening merit follow-up with serial contrast enhanced brain MRI for the early detection of an evolving occult hypothalamic-stalk lesion. CSF evaluation is recommended at presentation because elevated CSF hCG may precede MRI abnormalities.

    View details for Web of Science ID A1997WX55100009

    View details for PubMedID 9141516

  • Treatment of pediatric low-grade gliomas with a nitrosourea-based multiagent chemotherapy regimen JOURNAL OF NEURO-ONCOLOGY Prados, M. D., Edwards, M. S., Rabbitt, J., Lamborn, K., Davis, R. L., Levin, V. A. 1997; 32 (3): 235-241

    Abstract

    Between March 9, 1984 and January 29, 1992, 42 children with newly diagnosed symptomatic or previously diagnosed progressive low-grade gliomas received outpatient chemotherapy as their primary treatment. This study was a single arm, phase II trial designed to estimate the time to tumor progression and toxicity of this regimen. Procarbazine, 6-thioguanine, and dibromodulcitol were given before lomustine (CCNU) and vincristine was given 1 and 3 weeks after CCNU. Patients were treated for six treatment cycles or until the tumor progressed, whichever came first. Twenty-three patients had juvenile pilocytic astrocytomas, 11 had astrocytomas, one had oligodendroglioma, one had ganglioglioma, and six had radiographically diagnosed low-grade gliomas. The mean age of the patients was 5 years (median, 3 years). The median time to treatment failure was 132 weeks (95% confidence interval: 106, 186 weeks). Only eight patients have died the estimated 5-year survival rate is 78% (95% confidence interval, 60% 87%). There were two episodes of grade 4 neutropenia, and three episodes of grade 4 thrombocytopenia. This regimen was safe, able to be delivered in the outpatient setting, and produced prolonged periods of disease stabilization in children with low-grade gliomas.

    View details for Web of Science ID A1997WJ07900007

    View details for PubMedID 9049885

  • Primary intracerebral osteosarcoma: A case report JOURNAL OF NEURO-ONCOLOGY Bauman, G. S., Wara, W. M., Ciricillo, S. F., Davis, R. L., Zoger, S., Edwards, M. S. 1997; 32 (3): 209-213

    Abstract

    Primary intracerebral sarcomas are rare tumors. Malignant fibrous histiocytoma and fibrosarcoma are the predominant histologies. A 3 year old girl with a primary, intraparenchymal cerebral osteosarcoma, the second case reported in the literature, is described. Partial surgical resection, systemic chemotherapy and radio-surgery has provided tumor control at 18 months. Treatment issues are discussed.

    View details for Web of Science ID A1997WJ07900004

    View details for PubMedID 9049882

  • Treatment of high-risk medulloblastoma and other primitive neuroectodermal tumors with reduced dose craniospinal radiation therapy and multi-agent nitrosourea-based chemotherapy PEDIATRIC NEUROSURGERY Prados, M. D., Wara, W., Edwards, M. S., Ater, J., Rabbit, J., Lamborn, K., Davis, R., Levin, V. A. 1996; 25 (4): 174-181

    Abstract

    To investigate toxicity, and progression-free survival (PFS) of children and adults with newly diagnosed medulloblastoma, pineoblastoma, and other primitive neuroectodermal tumors (PNET) with a combined modality regimen of radiation therapy and adjuvant nitrosourea-based chemotherapy.Between 1984 and 1992, 34 evaluable patients with newly diagnosed tumors were treated with chemotherapy and radiotherapy according to a single-arm phase II study. One cycle of chemotherapy was given prior to and for 6 cycles following craniospinal radiotherapy (CSA). Procarbazine, 6-thioguanine, and dibromodulcitol were given before lomustine (CCNU) to enhance CCNU-induced tumor cell kill and to reduce alkyltransferase repair of ethylated DNA. Vincristine was given 1 and 3 weeks after CCNU to kill cells that began to cycle after the challenge of the first four drugs. Chemotherapy was given in the outpatient setting. CSA radiation was planned to deliver a dose of 54 Gy to the primary tumor site and 24 Gy to the rest of the neuroaxis. Additional radiation was given to bulky disease outside the primary site if present. Hydroxyurea was used during radiotherapy as a radiosensitizer.Patients treated included 27 with medulloblastoma, 5 with pineoblastoma, and 2 with supratentorial PNET. All but 3 medulloblastoma cases were considered high risk either because of bulky residual disease remaining after surgery and/or metastatic disease detected during staging. For the 34 patients, 24 have progressed, 20 have died. Overall estimated PFS was 55% at 3 years and 35% at 5 years. The 5-year survival estimate is 56%. One patient had inadequate staging to determine M stage. Of the remaining 33 patients, there were 19 patients who had metastatic disease at diagnosis (M1 or higher stage) who had a 3- and 5-year PFS of 42 and 21% respectively and 5-year survival of 42%. There were 14 patients who had negative staging (M0 stage) who had a 3- and 5-year PFS of 69 and 52% respectively and 5-year survival of 71%. Of the 27 patients with medulloblastoma, 15 had M1 or higher stage. These 15 patients had a 5-year PFS and overall survival of only 20 and 40% respectively. Medulloblastoma patients with M0 staging had a 5-year PFS and overall survival of 52 and 73% respectively. Overall toxicity was primarily due to mild hematological toxicity and related to the use of the chemotherapy.The results using this therapy in high-risk groups of patients does not offer any improvement over results reported in other recent studies. The reason for these results may be due to the lowered craniospinal radiation dose.

    View details for Web of Science ID A1996XQ73000002

    View details for PubMedID 9293544

  • Comparison of bromodeoxyuridine uptake and MIB 1 immunoreactivity in medulloblastomas determined with single and double immunohistochemical staining methods JOURNAL OF NEURO-ONCOLOGY Onda, K., Davis, R. L., Edwards, M. S. 1996; 29 (2): 129-136

    Abstract

    We examined the growth potential of 17 medulloblastomas by single and double immunohistochemical staining with bromodeoxyuridine (BUdR) and MIB 1, a monoclonal antibody for Ki-67 protein, in serial sections of ethanol-fixed, paraffin-embedded tissues; we also assessed the heterogeneity of the immunoreactivity in the tumors. In the most active areas, the BUdR labeling index (LI) was 6.8 to 26.9% (HCl hydrolysis) and 7.5 to 28.8% (microwave heating), and the MIB 1 proliferating cell index (PCl) was 14.9 to 56.5%. Linear regression analysis showed that the BUdR LI correlated with the MIB 1 PCI (p < 0.001). The ratio of MIB 1-positive to BUdR-positive cells was 2.2 +/- 0.4 by both single and double staining. BUdR-positive nuclei were heterogeneously distributed in all cases, especially in areas with scattered foci of necrosis. Three tumors had areas with many MIB 1-positive but few BUdR-positive nuclei; these areas were associated with recent tumor necrosis. However, in most of the tumors, the densities of BUdR-positive and MIB 1-positive cells changed concomitantly from area to area. These changes were clearly shown by double immunostaining. Thus, transcapillary passage of BUdR does not appear to be impeded in most medulloblastomas. This study suggests that MIB 1 immunostaining provides essentially the same data as BUdR labeling for assessing the proliferative potential of medulloblastomas.

    View details for Web of Science ID A1996VB11800002

    View details for PubMedID 8858517

  • Long-term follow-up after high-activity I-125 brachytherapy for pediatric brain tumors PEDIATRIC NEUROSURGERY Sneed, P. K., Russo, C., SCHARFEN, C. O., Prados, M. D., Malec, M. K., Larson, D. A., Lamborn, K. R., Lamb, S. A., Voss, B., Weaver, K. A., Phillips, T. L., Gutin, P. H., Wara, W. M., Edwards, M. S. 1996; 24 (6): 314-322

    Abstract

    A retrospective review including long-term follow-up (4.6-12.0 years) was performed of all 28 pediatric patients who underwent high-activity 125I brachytherapy at the University of California, San Francisco, for primary or recurrent brain tumors from 1980 until 1991. There were 4 glioblastomas, 11 high-grade nonglioblastoma multiforme (NGM) malignant gliomas, 10 contrast-enhancing low-grade NGM, 2 choroid plexus carcinomas, and 1 rhabdomyosarcoma. The 13 survivors included 7 of 8 patients with primary high-grade NGM, 2 of 3 patients with primary low-grade NGM, and 3 of 7 patients with recurrent low-grade NGM. Necrosis (with or without tumor) was identified in 17 of 22 reoperated patients. The mean Karnofsky performance status was 88 +/- 9 at the time of brachytherapy, 87 +/- 7 at 3 years, and 87 +/- 9 in 11 patients alive at 6-12 years. Brachytherapy is a useful modality for treating selected pediatric brain tumors, and although focal necrosis is a common sequela, it does not tend to have a major impact on the Karnofsky performance status, if the implant site is amenable to reoperation.

    View details for Web of Science ID A1996VX56800006

    View details for PubMedID 8988497

  • Skull base and calvarial deformities: Association with intracranial changes in craniofacial syndromes AMERICAN JOURNAL OF NEURORADIOLOGY Tokumaru, A. M., Barkovich, A. J., Ciricillo, S. F., Michael, S. B. 1996; 17 (4): 619-630

    Abstract

    To analyze the skull and brain malformations in patients with craniofacial syndromes.A retrospective analysis of imaging studies of 21 children with craniofacial anomalies (8 with Apert syndrome, 6 with Pfeiffer syndrome, 4 with Crouzon syndrome, 1 with Robert syndrome, 1 with Coffin-Lowry-syndrome, and 1 with Saethre-Chotzen syndrome) was carried out using CT (21 patients), MR imaging (9 patients), and MR venography (2 patients). A series of qualitative and quantitative assessments of the skull base and intracranial structures was performed.Skull base abnormalities were present in all patients. Intracranial abnormalities included ventriculomegaly, frank hydrocephalus, callosal anomalies, hypoplasia/absence of the septum pellucidum, hypoplasia/dysplasia of the hippocampus, dysplasias or distortions of the cerebral cortex, and parenchymal hemorrhage. The anomalies of the corpus callosum, septum pellucidum, and hippocampus appeared primary, whereas the others may have been the result of brain distortion by the calvarial anomaly. MR imaging was more useful than CT for evaluating brain abnormalities. In the two patients in whom it was performed, MR venography showed anomalies of the venous system, indicating that venous anomalies, possibly related to the skull base hypoplasia, may contribute to the intracranial abnormalities.A wide range of neuroimaging abnormalities are present in the craniofacial syndromes. Some of these are clearly primary, whereas others appear to be related to the small skull base and sutural synostoses. MR venography may prove useful in defining the cause of some of the associated anomalies.

    View details for Web of Science ID A1996UF80100003

    View details for PubMedID 8730180

  • Gamma knife radiosurgery in children PEDIATRIC NEUROSURGERY Baumann, G. S., Wara, W. M., Larson, D., Sneed, P. K., Gutin, P. H., Ciricillo, S. F., McDermott, M. W., Park, E., Stalpers, L. J., Verhey, L. J., Smith, V., Petti, P. L., Edwards, M. S. 1996; 24 (4): 193-201

    Abstract

    52 pediatric patients were treated with radiosurgery at the University of California, San Francisco. Arteriovenous malformations were treated in 27 patients. Complete obliteration was noted in 4 of 12 patients imaged more than 2 years after radiosurgery. Arteriovenous malformation rebleed was noted in 1 patient. Symptomatic T2 changes were noted in 2 patients. Among 29 neoplasms treated in 25 patients, local control was noted in 5 of 7 low-grade gliomas, 5 of 14 high-grade gliomas, 4 of 5 craniopharyngiomas and 3 of 3 sarcomas. Three patients treated for neoplasms developed necrosis after radiosurgery.

    View details for Web of Science ID A1996VE18500005

    View details for PubMedID 8873161

  • Evolution of high-intensity basal ganglia lesions on T1-weighted MR in neurofibromatosis type 1 AMERICAN JOURNAL OF NEURORADIOLOGY Terada, H., Barkovich, A. J., Edwards, M. S., Ciricillo, S. F. 1996; 17 (4): 755-760

    Abstract

    To characterize the temporal evolution of the foci of T1 shortening in basal ganglia lesions in patients with neurofibromatosis type 1 (NF-1).A retrospective review of MR images of 37 patients with NF-1 revealed 8 patients in whom regions of T1 shortening were noted in the basal ganglia. We reviewed sequential images obtained in these selected patients with special attention to chronological changes in the foci of T1 shortening and their relationship to changes on T2-weighted images.Regions of short T1 in the globus pallidus were observed in 8 patients. In 2 of 3 patients in whom foci of T1 shortening were not identified on the initial imaging study, T1 shortening developed and T2 prolongation diminished after an initial increase. In the third patient, T1 and T2 prolongation appeared simultaneously. Sequential scans in the other 5 patients, in whom areas of increased signal intensity in the globus pallidus were present on both T1-weighted and T2-weighted images on the initial MR examination, showed a diminution in the size of the region of T2 prolongation in 2 patients, an increase in the size of the region of T2 prolongation in 1 patient, a mixed pattern of change in the size of the region of T2 prolongation in 1 patient, and no change in the region of T2 prolongation in 1 patient. During the periods of these T2 changes, the areas of T1 shortening showed no significant interval change.The foci of prolonged T2 relaxation in the basal ganglia appear to evolve in a manner similar to the foci of T2 prolongation in the white matter of the posterior fossa. However, the corresponding foci of short T1 in the basal ganglia may evolve with a different time course. In some patients, the foci of short T1 develop at a later time than the T2 prolongation and progress; these foci of short T1 do not appear to regress over periods as long as 90 months. Possible causes of the T1 shortening are remyelination and calcification.

    View details for Web of Science ID A1996UF80100023

    View details for PubMedID 8730197

  • Lower urinary tract function in ambulatory children with spina bifida BRITISH JOURNAL OF UROLOGY Mevorach, R. A., Bogaert, G. A., Baskin, L. S., Lazzaretti, C. C., Edwards, M. S., Kogan, B. A. 1996; 77 (4): 593-596

    Abstract

    To investigate lower urinary tract function in ambulatory children with myelomeningocele.The urological course of 45 children with myelomeningocele who walked either independently (19 children) or with ankle-foot orthotics (26 children) was reviewed. Follow-up ranged from 9 months to 13.5 years (mean 4.75 years).A normal pattern of voiding was observed both clinically and during urodynamic evaluation in only three of the 45 children, with the remainder displaying neurogenic lower urinary tract dysfunction. The independent walkers and those with orthotics did not differ in the spectrum of lower urinary tract dysfunction or other variables. Those patients with persistent incontinence underwent an initial urodynamic evaluation when older (mean 3.7 years versus 6.4 weeks in those who were continent).Ambulatory children with myelomeningocele suffer the full spectrum of lower urinary tract dysfunction. Given the potential danger of untreated lower urinary tract dysfunction, ambulatory children with myelomeningocele should receive the same diagnostic and therapeutic attention as their peers with more overt neurological deficits.

    View details for Web of Science ID A1996UF13700022

    View details for PubMedID 8777626

  • Radiologic classification of brain stem tumors: Correlation of magnetic resonance imaging appearance with clinical outcome PEDIATRIC NEUROSURGERY Fischbein, N. J., Prados, M. D., Wara, W., Russo, C., Edwards, M. S., Barkovich, A. J. 1996; 24 (1): 9-23

    Abstract

    Although tumors of the brain stem have traditionally been classified as a single entity, these tumors are increasingly being recognized as a heterogeneous group, with some subgroups having better prognoses for long-term survival. Although several systems for classification of brain stem tumors have been proposed, none have been based on data derived from contrast-enhanced magnetic resonance (MR) imaging. In this review, we present a classification scheme based on our review of the literature and of the MR scans of 64 patients with brain stem tumors. In addition, we assess the contribution of gadolinium to the classification of brain stem tumors and correlate the various tumor subtypes, based on MR appearance, with prognosis. Our results suggest that the most important factor in determining prognosis based on MR characteristics is whether the tumor is diffuse or focal. Focal tumors have an excellent prognosis regardless of the site of tumor origin. Diffuse tumors of the mesencephalon and pons have a significantly poorer prognosis than focal tumors (p = 0.0013), with diffuse pontine tumors having the worst prognosis. Differentiation of diffuse and focal medullary tumors was difficult, possibly explaining the lack of significant difference in the survival of patients with diffuse versus focal medullary tumors. The presence or absence of enhancement after the administration of paramagnetic contrast has no significant relation with outcome, overall or within specific tumor subgroups.

    View details for Web of Science ID A1996UT87800004

    View details for PubMedID 8817611

  • STEREOTAXIC INSERTION OF AN OMMAYA RESERVOIR - TECHNICAL NOTE CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES McDermott, M. W., Ciricillo, S. F., Gutin, P. H., Edwards, M. S. 1995; 22 (3): 235-238

    Abstract

    Stereotactic insertion of catheters into deep-seated tumors or developmental cysts is easily accomplished, but connecting the catheter to an Ommaya reservoir while maintaining catheter position can be difficult. We describe a technique for easy placement of a catheter-Ommaya reservoir construct with one pass.Standard stereotactic imaging is performed. The distance from the outer table of the skull to the target point is measured. A catheter-Ommaya reservoir construct is assembled to this length and directed to the target position with a standard Cosman-Robert-Wells (CRW) stereotactic frame.Use of this technique placed catheters into tumor or developmental cysts accurately and with no surgical complications in 12 patients.This technique is simple, safe, reliable, and requires no special equipment. It avoids the risk of dislodging the catheter when it is being connected to the Ommaya reservoir, reducing the chances of cyst leakage and collapse.

    View details for Web of Science ID A1995RQ31800011

    View details for PubMedID 8529178

  • RADIATION-THERAPY FOR PRIMARY INTRACRANIAL GERM-CELL TUMORS INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Wolden, S. L., Wara, W. M., Larson, D. A., Prados, M. D., Edwards, M. S., Sneed, P. K. 1995; 32 (4): 943-949

    Abstract

    To evaluate the diagnosis, therapy, and survival of patients with intracranial germ-cell tumors. To define the role of prophylactic craniospinal irradiation and chemotherapy necessary to impact on survival.Forty-eight patients with surgically confirmed or suspected primary intracranial germ-cell tumors treated at UCSF between 1968-1990 were reviewed. Thirty-four patients had a pathologic diagnosis, including 24 germinomas, 3 malignant teratomas, 2 choriocarcinomas, 1 embryonal carcinoma, 1 endodermal sinus tumor, and 3 mixed tumors. Information obtained included histology, location, cerebrospinal fluid (CSF) cytology, alpha-fetoprotein (AFP), and beta-human chorionic gonadotropin (B-HCG), metastatic evaluation, radiation details, survival, and sites of failure. Minimum follow-up time was 2 years and ranged to a maximum of 24 years, with a median of 8 years.Median age at diagnosis was 16 years with 36 males and 12 females. Ten of 32 patients had elevated B-HCG at diagnosis; 6 of 29 had elevations of AFP. Cerebrospinal fluid cytology was negative in 35 of 36 patients evaluated; myelography or spinal MRI was positive in only 1 of 31 patients studied. Five-year actuarial disease-free survival after irradiation was 91% for germinomas, 63% for unbiopsied tumors, and 60% for nongerminoma germ-cell tumors with doses of 50-54 Gy to the local tumor site with or without whole-brain or whole-ventricular irradiation. Routine prophylactic cranio-spinal axis irradiation was not given with a spinal only failure rate of 2%. Eleven of 48 patients have expired, with an actuarial 5-year survival rate of 100% for germinomas, 79% for nonbiopsied tumors, and 80% for nongerminoma germ-cell tumors.With complete diagnostic craniospinal evaluation, spinal irradiation is not necessary. Cure rates for germinomas are excellent with irradiation alone. Multidrug chemotherapy is necessary with irradiation for nongerminoma germ-cell tumors. Histology is the most important prognostic factor; therefore, all patients should have surgical conformation of their diagnosis so that appropriate treatment can be given.

    View details for Web of Science ID A1995RL55500005

    View details for PubMedID 7607968

  • THE TREATMENT OF BRAIN-STEM AND THALAMIC GLIOMAS WITH 78 GY OF HYPERFRACTIONATED RADIATION-THERAPY INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Prados, M. D., Wara, W. M., Edwards, M. S., Larson, D. A., Lamborn, K., Levin, V. A. 1995; 32 (1): 85-91

    Abstract

    To see whether increasing the dose of hyperfractionated radiation therapy from 72 to 78 Gy would increase survival time in patients with gliomas, particularly those with brain stem or thalamic tumors.Seventy-eight patients with a clinical and radiographic diagnosis of a brain stem or thalamic glioma were enrolled in a trial to receive 78 Gy (1.0 Gy twice a day). Six patients with disease in other sites were also treated. The initial response to therapy was determined by comparing pretreatment magnetic resonance images and neurological examinations with those obtained within 2 weeks of completing therapy; subsequent responses were determined from bimonthly follow-up images. Time-to-tumor progression was measured from the date radiation therapy began until the date of documented radiographic or clinical progression. Survival time was measured from the date radiation therapy began until the date of death. Cox proportional hazards analysis was used to estimate the effects of specific variables on survival.Of 81 evaluable patients, 68 received > or = 76 Gy, 10 received between 70 and 75 Gy, and 3 received between 60 and 68 Gy. The overall response or stabilization rate was 70.4%. Tumor size decreased in 30.8% of patients; 39.5% had stable disease, and 29.6% had immediate progression. The median survival time was 12.7 months (16.1 months for adults and 10.8 months for children). The median time to tumor progression was 9.0 months (11.4 months for adults and 8.4 months for children). A duration of symptoms < or = 2 months and a diffuse lesion were each associated with shorter survival and progression times.For patients with brain stem or thalamic gliomas, increasing the dose of radiation therapy from 72 to 78 Gy did not significantly improve survival. Different treatment strategies are clearly needed.

    View details for Web of Science ID A1995QU49000011

    View details for PubMedID 7619124

  • NEUROENDOSCOPY WESTERN JOURNAL OF MEDICINE McDermott, M. W., Ciricillo, S. F., Edwards, M. S. 1995; 162 (3): 261-262

    View details for Web of Science ID A1995QN08700016

    View details for PubMedID 7725717

  • A SUBTLE SIGN OF SPINAL-CORD LIPOMA CLINICAL PEDIATRICS Koch, S. E., Koch, T. K., Edwards, M. S. 1995; 34 (3): 156-157

    View details for Web of Science ID A1995QM64800007

    View details for PubMedID 7774142

  • RADIATION-INDUCED TELANGIECTASIA IN THE BRAIN SIMULATES CRYPTIC VASCULAR MALFORMATIONS AT MR-IMAGING RADIOLOGY GAENSLER, E. H., Dillon, W. P., Edwards, M. S., Larson, D. A., Rosenau, W., Wilson, C. B. 1994; 193 (3): 629-636

    Abstract

    To analyze the magnetic resonance (MR) imaging, clinical, and pathologic features of radiation-induced telangiectasia of the brain.The clinical and radiation therapy records were reviewed of 20 patients who developed focal hypointense lesions on T2-weighted MR images obtained after radiation therapy of the central nervous system. Pathologic material was reviewed in six patients.Eleven patients had solitary lesions, and nine had multiple foci on MR images. Fourteen of the 20 patients were less than 20 years old. The appearance ranged from small hypointense foci to larger regions of acute hemorrhage. Hematomas occurred at the site of a previously identified focus of T2 shortening in five patients. Pathologic findings included ectatic thin-walled vessels surrounded by hemosiderin and gliosis, with minimal evidence of necrosis.Radiation-induced telangiectasia in the brain results in varying amounts of hemorrhage and, occasionally, parenchymal hematomas, and may appear similar to cryptic vascular malformations on T2-weighted MR images.

    View details for Web of Science ID A1994PT55300012

    View details for PubMedID 7972799

  • PROGRESSION OF MULTIPLE CRYPTIC VASCULAR MALFORMATIONS ASSOCIATED WITH ANOMALOUS VENOUS DRAINAGE - CASE-REPORT JOURNAL OF NEUROSURGERY Ciricillo, S. F., Dillon, W. P., Fink, M. E., Edwards, M. S. 1994; 81 (3): 477-481

    Abstract

    The case of a young girl with a pericallosal venous malformation associated with multiple cryptic vascular malformations (CVM's) is described. The presenting cryptic malformation, which hemorrhaged, was completely excised, but the venous malformation was not. Routine follow-up magnetic resonance images obtained over the past 9 years have documented the development of multiple new cryptic malformations along the radicles of the venous malformation. Magnetic resonance imaging and cerebral angiography revealed venous outflow obstruction at the junction of the venous malformation with the straight sinus. The association of CVM's with anomalous venous drainage patterns and the role of venous hypertension in the pathogenesis of cryptic malformations are discussed. This case suggests that CVM's associated with a venous malformation may recur and new ones may develop if the venous malformation is not excised, particularly if venous hypertension is also present. The likelihood of a surgical cure in these patients may depend on complete excision of both anomalies, which is rarely feasible because of the potentially devastating results of resecting a venous malformation. Alternative treatments for patients with both types of lesions are discussed.

    View details for Web of Science ID A1994PC76200021

    View details for PubMedID 8057159

  • TREATMENT OPTIONS AND PROGNOSIS FOR MULTICENTRIC JUVENILE PILOCYTIC ASTROCYTOMA JOURNAL OF NEUROSURGERY Mamelak, A. N., Prados, M. D., OBANA, W. G., Cogen, P. H., Edwards, M. S. 1994; 81 (1): 24-30

    Abstract

    Little is known about the risk of developing multicentric disease in patients with juvenile pilocytic astrocytoma (JPA), and even less about its prognosis. Only five cases have been reported. Between 1986 and 1992, the authors treated 90 patients with either primary or recurrent JPA, 11 of whom developed multicentric spread. Ten patients had primary tumors in the hypothalamic region, eight were under 4 years of age at initial diagnosis, all had initially undergone a subtotal resection or biopsy, and 10 received postoperative multiagent chemotherapy or irradiation for residual disease. Multicentric spread was discovered immediately to 108 months after initial diagnosis; nine patients were asymptomatic at the time. Most patients received chemotherapy for the multicentric disease, which was found throughout the craniospinal axis. During 21 to 148 months of follow-up monitoring, seven patients had stabilization or regression of multicentric disease and four died. Patients with hypothalamic region tumors were 23 times more likely to develop multicentric spread than were those with primary tumors located elsewhere (p < 0.001). Based on this review, it is concluded that multicentric spread of JPA occurs more frequently than was previously recognized. In patients with subtotally resected JPA and several years of follow-up review via magnetic resonance imaging, the incidence of recurrence in a site different from the original was 12%. Patients with subtotally resected JPA in the hypothalamic region should be considered to be at high risk for developing multicentric spread. Chemotherapy appears useful in stabilizing multicentric disease. Earlier detection and intervention may result in longer disease-free survival in patients with multicentric spread of JPA.

    View details for Web of Science ID A1994NR68200005

    View details for PubMedID 8207524

  • INTRACRANIAL MENINGIOMAS OF THE FIRST 2 DECADES OF LIFE JOURNAL OF NEUROSURGERY Germano, I. M., Edwards, M. S., Davis, R. L., Schiffer, D. 1994; 80 (3): 447-453

    Abstract

    Meningiomas arising in the first two decades of life are uncommon and their characteristics are controversial. Some authors believe meningiomas in younger patients occur in different locations, have more malignant histological features, and have a worse prognosis than those in adults. To address this controversy, the authors retrospectively reviewed 23 cases of meningiomas in patients under 21 years of age at diagnosis who were operated on at the University of Turin (1948 to 1990) or at the University of California, San Francisco (1970 to 1989). These tumors represented 2.9% of all tumors in this age group and 1.8% of all meningiomas during the study period at the two institutions. There were 14 males and nine females. The mean age at surgery was 13.3 +/- 5.6 years; nine cases occurred in the first decade and 14 in the second. The most common neurological symptoms were a focal neurological deficit (33%) and seizures (25%). Seventy percent of the tumors were supratentorial. A gross total resection was performed in 60% of the cases. Histologically, the majority (74%) of the tumors were meningothelial or mixed. An increased number of mitoses was observed in 33% of the tumors, focal necrosis in 29%, and invasion of adjacent brain in 14%; however, none of the tumors was classified as a Grade III (anaplastic) meningioma. All patients are alive without evidence of recurrent disease 3 to 22 years (mean +/- standard deviation: 10 +/- 7.3 years) after surgery. This study confirms the rarity of meningiomas of the first two decades of life and the absence of the female predominance associated with meningiomas in adults. The location and histological features of these tumors are similar to those in adults; they have a low recurrence rate, and the outcome and survival rate are excellent.

    View details for Web of Science ID A1994MY48300005

    View details for PubMedID 8113857

  • HYPERFRACTIONATED CRANIOSPINAL RADIATION-THERAPY FOR PRIMITIVE NEUROECTODERMAL TUMORS - EARLY RESULTS OF A PILOT-STUDY INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Prados, M. D., Wara, W. M., Edwards, M. S., Cogen, P. H. 1994; 28 (2): 431-438

    Abstract

    To report the early results of hyperfractionated craniospinal radiation therapy with and without adjuvant chemotherapy for primitive neuroectodermal brain tumors (PNETs).Thirty-nine patients with PNETs were classified as good-risk (23) or poor-risk (16), based on postoperative magnetic resonance imaging and a cytological examination of cerebrospinal fluid. All patients received hyperfractionated craniospinal radiation therapy; poor-risk patients subsequently received adjuvant chemotherapy with cisplatin, lomustine, and vincristine. The first six patients received 72 Gy to the primary tumor site and 24 Gy to the rest of the craniospinal axis. Subsequent patients received 30 Gy to the craniospinal axis.During a median of 1.9 years of follow-up (range 4 months to 3.5 years), there have been ten treatment failures in 39 patients, five in the good-risk group and five in the poor-risk group. Three failures occurred in the primary tumor site in areas that received 72 Gy; two were in poor-risk patients with residual disease after surgery; one was in a good-risk patient who had a gross total resection. Three failures occurred in the spine and craniospinal fluid of patients treated with 24 Gy. Four occurred in areas treated to 30 Gy; two of these were in areas thought to be undertreated because of treatment planning errors. Adjuvant chemotherapy was difficult to give to poor-risk patients because of poor bone marrow recovery, even with relatively low doses of lomustine (75 mg/m2).We think a dose of 24 Gy to the craniospinal axis is inappropriate because three of the six patients who received it had treatment failures outside the primary site. Whether 30 Gy is an appropriate dose for good-risk patients is still unclear. Even after a dose of 30 Gy, chemotherapy was difficult to give; this potentially limits the impact of adjuvant chemotherapy in poor-risk patients. Further follow-up is necessary to evaluate the use of hyperfractionated radiation therapy alone or with chemotherapy in patients with PNETs.

    View details for Web of Science ID A1994MP98100013

    View details for PubMedID 8276658

  • PEDIATRIC CRYPTIC VASCULAR MALFORMATIONS - PRESENTATION, DIAGNOSIS AND TREATMENT PEDIATRIC NEUROSURGERY Ciricillo, S. F., Cogen, P. H., Edwards, M. S. 1994; 20 (2): 137-147

    Abstract

    Since the advent of magnetic resonance (MR) imaging, angiographically occult or 'cryptic' vascular malformations (CVMs) have been detected with increasing frequency in the pediatric population. The natural history of these lesions is uncertain and treatment remains controversial. We respectively reviewed the presentation, radiology, treatment and outcome of 37 pediatric patients with CVMs seen at our institution between 1982 and 1992. MR imaging was diagnostic in all patients studied. Angiography was negative in 20 of 21 patients studied, while 1 teenage girl was found to have a venous malformation. Total surgical excision was the treatment goal in all patients presenting with symptomatic CVMs. There has been no surgical mortality. Perioperative complications occurred in one third of the patients but quickly resolved in most cases. Only 2 patients with multiple CVMs, including brainstem lesions, who presented with progressive neurologic deficits were clearly worse following surgery. Six of seven patients with radiation-induced CVMs have remained asymptomatic with close radiographic follow-up, while 1 patient with a hemorrhage has required surgical evacuation. We conclude that CVMs occur more commonly in the pediatric population than previously assumed. Patients presenting with seizures or hemorrhage should undergo craniotomy with the goal of complete excision. Radiation therapy plays no role in the treatment of these lesions and may actually result in their formation. Careful clinical and radiological follow-up is critical to assess the completeness of surgical removal and to evaluate progression of lesions in patients with multiple or radiation-induced CVMs treated conservatively.

    View details for Web of Science ID A1994MY04800003

    View details for PubMedID 8161487

  • FOCAL BRAIN-STEM ASTROCYTOMAS CAUSING SYMPTOMS OF INVOLVEMENT OF THE FACIAL-NERVE NUCLEUS - LONG-TERM SURVIVAL IN 6 PEDIATRIC CASES JOURNAL OF NEUROSURGERY Edwards, M. S., Wara, W. M., Ciricillo, S. F., Barkovich, A. J. 1994; 80 (1): 20-25

    Abstract

    Six children with a history of isolated facial nerve dysfunction or dizziness and nausea were treated for brain-stem glioma between 1984 and 1992. Computerized tomography and/or magnetic resonance (MR) imaging showed a focal, uniformly enhancing mass involving the facial nerve nucleus of the pons. All patients underwent biopsy; the histological diagnosis was juvenile pilocytic astrocytoma in five cases. In the remaining case the biopsy was nondiagnostic, although the surgeon believed that the lesion was a glioma. Postoperatively, five patients underwent conventional focal megavoltage radiation therapy (180 to 200 cGy/day) over a period of 5 1/2 weeks to a total dose of approximately 5400 cGy. One child's family refused radiation therapy; she remained well and stable for 4 years, despite persistent facial weakness, and was eventually lost to follow-up review. Four irradiation-treated patients had complete resolution of their tumors on MR images and have had no evidence of neuropsychological or neuroendocrinological deficits during 4 1/2 to 8 years of follow-up evaluation. Patients whose neuroradiological studies show a lesion resembling those in this series should undergo biopsy and, if the histology of a low-grade tumor (in particular, a juvenile pilocytic astrocytoma) is confirmed, should then receive focal radiation therapy with conventional megavoltage dosages.

    View details for Web of Science ID A1994MQ15400003

    View details for PubMedID 8271016

  • SELECTED INDICATIONS FOR AND APPLICATIONS OF MAGNETIC-RESONANCE ANGIOGRAPHY IN CHILDREN PEDIATRIC NEUROSURGERY Maas, K., Barkovich, A. J., Dong, L., Edwards, M. S., Piecuch, R. E., Charlton, V. 1994; 20 (2): 113-125

    Abstract

    The purpose of this study was to investigate the efficacy and practicality of magnetic resonance angiography (MRA) in evaluating pediatric cerebrovascular disorders. A retrospective evaluation was performed of MR angiograms in 20 pediatric patients with cerebrovascular pathology. When appropriate, comparisons were made with duplex ultrasonography or conventional catheter angiography. MRA accurately assessed the patency of carotid reanastomoses in 8 babies who had previously undergone extracorporeal membrane oxygenation (ECMO). In 6 patients with moyamoya syndrome, MRA accurately evaluated stenotic intracranial carotid and circle of Willis arteries and progressive enlargement of the superficial temporal and middle cerebral arteries after revascularization procedures, and thus obviated the need for sequential angiograms. Thrombi and emboli were identified in 4 of 5 patients with symptoms and imaging evidence of an acute stroke. Two-dimensional time-of-flight MR venograms, acquired in both axial and coronal planes, were useful for preoperative venous mapping in a patient with an occipital encephalocele and detecting venoocclusive disease. MRA provided diagnostically useful information in a spectrum of pediatric cerebrovascular disorders. It can be used as the initial vascular imaging modality for patients with imaging evidence of acute cerebrovascular event, to evaluate progression of chronic vasoocclusive disease, to evaluate vessel patency following intracranial revascularization surgery, and for visualization of the venous circulation.

    View details for Web of Science ID A1994MY04800001

    View details for PubMedID 8161486

  • TREATMENT OF GIANT INTRADURAL (PERIMEDULLARY) ARTERIOVENOUS-FISTULAS NEUROSURGERY Halbach, V. V., Higashida, R. T., Dowd, C. F., Fraser, K. W., Edwards, M. S., Barnwell, S. L., Livingston, K., Hopkins, L. N., Berenstein, A. 1993; 33 (6): 972-980

    Abstract

    Ten patients with giant intradural spinal arteriovenous fistulas (perimedullary Types II and III) were treated with embolization alone (three patients) or in combination with surgery (seven patients). Their ages at the time of treatment ranged from 2 to 40 years, with a mean of 19.5 years. The indications for treatment included progressive myelopathy in five patients, spinal subarachnoid hemorrhage in four, and acute paraplegia in one. Associated conditions included Rendu-Osler-Weber syndrome in two patients, and Cobb's syndrome in two patients. In one patient, the cause of the fistula may have been related to epidural anesthesia traumatizing a low tethered cord. Angiographically, the fistulas were subclassified in three groups: a single-hole fistula supplied by a single feeding medullary artery (three patients); a single-hole fistula supplied by multiple medullary arteries (three patients); and multiple separate fistulas supplied by multiple medullary arteries (four patients). Eight patients were classified as perimedullary Type III and two as perimedullary Type II. Embolic agents were delivered from transarterial routes in 14 procedures and transvenous routes in 2 procedures. A total of 16 embolizations and 8 operations were performed in 10 patients. Seven patients were cured of their fistula (as demonstrated by angiography), two patients had 5% residual filling and are scheduled for future therapy. One refused a follow-up angiographic examination. Complications related to embolization included rupture of the anterior spinal artery by a detachable balloon, resulting in transient worsening of paraplegia with recovery to baseline. Transient worsening of symptoms after surgery was common, but all patients returned to baseline or better. Dramatic improvement was observed in four patients.(ABSTRACT TRUNCATED AT 250 WORDS)

    View details for Web of Science ID A1993MK21300003

    View details for PubMedID 8134010

  • MANAGEMENT OF INTRACRANIAL AND SPINAL-CORD VASCULAR-LESIONS IN CHILDREN WESTERN JOURNAL OF MEDICINE Edwards, M. S., Halbach, V. V. 1993; 158 (2): 182-182

    View details for Web of Science ID A1993KM08800015

    View details for PubMedID 8434474

  • Pineal tumors. Neurosurgery clinics of North America Baumgartner, J. E., Edwards, M. S. 1992; 3 (4): 853-862

    Abstract

    Tissue diagnosis is necessary for optimal treatment of pineal region tumors in children. Preoperative staging should include craniospinal MR imaging with and without gadolinium DTPA enhancement, CSF sampling for cytology, and measurement of biologic tumor markers in serum and CSF. Surgical approach is determined by results of preoperative MR imaging and the extent of resection by the results of staging and intraoperative frozen-section histopathologic evaluation. There is no longer a role for the radiation test dose (2000 cGy) in the management of these tumors. Postoperative treatment is based on histopathology and extent of disease. Benign tumors are treated with surgery only, and nondisseminating focal tumors with surgery and focal radiation therapy. Non-germinoma malignant germ cell tumors are best treated with neoadjuvant chemotherapy followed by radiation therapy given focally for focal disease; craniospinal radiation therapy is reserved for patients with evidence of disseminated disease at the completion of induction chemotherapy.

    View details for PubMedID 1392580

  • PROLIFERATIVE CHARACTERISTICS OF JUVENILE PILOCYTIC ASTROCYTOMAS DETERMINED BY BROMODEOXYURIDINE LABELING NEUROSURGERY Ito, S., Hoshino, T., Shibuya, M., Prados, M. D., Edwards, M. S., Davis, R. L., Sawaya, R., Morantz, R. A. 1992; 31 (3): 413-419

    Abstract

    Bromodeoxyuridine (BUdR) labeling studies were performed to characterize the biological and clinical behavior of 50 juvenile pilocytic astrocytomas (JPAs) from 47 patients. Each patient received an i.v. infusion of BUdR before tumor resection; the excised tumor specimens were stained by the immunoperoxidase method with anti-BUdR monoclonal antibody to determine the BUdR labeling index (LI), or percentage of S-phase cells. The BUdR LI ranged from 0.22 to 4.3% (less than 1% in 34 and greater than or equal to 1% in 16; mean +/- SE, 1.05 +/- 0.13%). Tumors from younger patients often had higher LIs, but as the age of the patients increased, the frequency of tumors with LIs greater than or equal to 1% decreased. Tumors from male patients had higher LIs than those from female patients (1.36 +/- 0.20% [SE] vs. 0.75 +/- 0.13%; P less than 0.01), and tumors in the cerebellum had higher LIs than those in the hypothalamus (1.39 +/- 0.24% vs. 0.87 +/- 0.15%; P less than 0.05). The LI did not correlate with the gross appearance of the tumor (solid or cystic) or with outcome after the initial diagnosis. Overall, there was no difference in the LIs of primary and recurrent tumors. Four tumors (3 primary and 1 recurrent) that recurred after subtotal resection had a higher mean LI than 32 tumors that did not recur after subtotal resection (2.6 +/- 0.7% vs. 0.74 +/- 0.09%; P less than 0.005). None of 14 totally resected tumors (mean LI, 1.3 +/- 0.2%) has recurred.(ABSTRACT TRUNCATED AT 250 WORDS)

    View details for Web of Science ID A1992JN83400005

    View details for PubMedID 1407423

  • CELL-KINETICS OF MEDULLOBLASTOMAS CANCER Ito, S., Hoshino, T., Prados, M. D., Edwards, M. S. 1992; 70 (3): 671-678

    Abstract

    Cell kinetics and clinical behavior were correlated for 22 primary and 10 recurrent or metastatic medulloblastomas from 30 patients.Twenty-six patients received bromodeoxyuridine (BUdR) intravenously during craniotomy; excised specimens were stained by the immunoperoxidase method. The BUdR labeling index (LI) was calculated. Four patients received a pulse of tritiated thymidine; LI was calculated autoradiographically.The mean LI for 32 tumors (11.7 +/- 1.3% standard error) indicated high proliferative potential. LI appeared higher in tumors from younger patients and those in the cerebellar hemisphere as compared with those in the cerebellar vermis. LI did not correlate with survival time. In six BUdR-labeled tumors labeled with iododeoxyuridine, the S-phase duration was 6.1-11.3 hours (mean, 8.0 +/- 0.8 hours); the potential doubling time was 25-82 hours. The actual doubling time, estimated in three cases from serial imaging, was 20-24 days. A cell loss factor of approximately 0.90 was assumed.A high LI may reflect rapid medulloblastoma growth, but survival seemed more dependent on sensitivity to radiation therapy.

    View details for Web of Science ID A1992JF19600019

    View details for PubMedID 1623482

  • PREDICTING THE RECURRENCE OF EPENDYMOMAS FROM THE BROMODEOXYURIDINE LABELING INDEX CHILDS NERVOUS SYSTEM Asai, A., Hoshino, T., Edwards, M. S., Davis, R. L. 1992; 8 (5): 273-278

    Abstract

    The usefulness of histopathological grading in predicting the prognosis of patients with ependymomas is controversial. To clarify the discrepancy between the histological malignancy and the prognosis of these tumors, we estimated the proliferative potential of 32 intracranial and intraspinal ependymomas and correlated the findings with the clinical behavior. Each patient received an intraoperative infusion of bromodeoxyuridine (BUdR, 200 mg/m2 i.v.) before tumor removal; the BUdR labeling index (LI), or percentage of BUdR-labeled cells, was determined immunohistochemically in excised specimens. The mean BUdR LI (+/- SD) of intracranial malignant ependymomas was 4.1 +/- 2.8%. Nonmalignant intracranial and intraspinal ependymomas and subependymomas had mean LIs of 1.5 +/- 0.9%, 1.1 +/- 0.3%, and less than 1%, respectively. Overall, 44% of the tumors recurred. There were no statistically significant differences in the recurrence rates of intracranial and intraspinal ependymomas, including subependymomas (43% and 44%, respectively), or of intracranial ependymomas with LIs greater than 1.0% and less than 1.0% (67% and 44%, respectively). However, the early recurrence rate (within 24 months after treatment) of tumors with LIs greater than 1.0% was higher than that of tumors with LIs of less than 1.0% (100% vs. 25%, P less than 0.05). The BUdR LI also showed a statistically significant inverse correlation with the time to recurrence. These findings indicate that BUdR LI reflects the proliferative potential of individual ependymomas and can be used to help predict the recurrence and estimate the prognosis of these tumors.

    View details for Web of Science ID A1992JJ83600007

    View details for PubMedID 1394266

  • PROLIFERATIVE POTENTIAL AND OUTCOME IN PEDIATRIC ASTROCYTIC TUMORS JOURNAL OF NEURO-ONCOLOGY Prados, M. D., Krouwer, H. G., Edwards, M. S., Cogen, P. H., Davis, R. L., Hoshino, T. 1992; 13 (3): 277-282

    Abstract

    In 43 pediatric patients (29 male, 14 female) with primary astrocytic tumors of the central nervous system (CNS), the correlation was evaluated between outcome and proliferative potential, measured by the bromodeoxyuridine (BrdU) labeling index (LI). Twenty-five patients had low-grade gliomas, 13 had anaplastic gliomas, and 5 had glioblastomas multiforme (GBM). All patients underwent surgery; 37 also had chemotherapy, radiation therapy, or both. The median BrdU LIs were less than 1% (range 0-9.3%) in low-grade gliomas, 2.3% (range 0-21.2%) in anaplastic gliomas, and 7.7% (range 0-21.3%) in GBM. Seven of eight patients with BrdU LI greater than 5% have died (median survival 29 weeks). Median survival has not been reached in patients with BrdU LI less than 1% (19/22 alive) or between 1% and 5% (12/13 alive) after median follow-up periods of 165 and 120 weeks, respectively. A high BrdU LI correlated with short survival (p = 0.0001); the association between malignant histology and short survival was weaker (p = 0.019). BrdU LI is therefore a significant predictor of outcome in patients with primary CNS astrocytomas and appears to be a stronger predictor than histology in patients with low-grade and anaplastic gliomas. More patients need to be studied to confirm these preliminary observations.

    View details for Web of Science ID A1992JE21000011

    View details for PubMedID 1325544

  • EVOLUTION OF WHITE MATTER LESIONS IN NEUROFIBROMATOSIS TYPE-1 - MR FINDINGS AMERICAN JOURNAL OF ROENTGENOLOGY Sevick, R. J., Barkovich, A. J., Edwards, M. S., Koch, T., Berg, B., Lempert, T. 1992; 159 (1): 171-175

    Abstract

    To characterize further the evolution of white matter lesions in neurofibromatosis type 1, we reviewed 68 MR images in 43 patients (age, 1-31 years), including 25 follow-up studies (mean interval, 27 months). Lesion number, location, morphology, signal characteristics, and contrast enhancement were assessed. Lesion characteristics and changes thereof were correlated with the patients' ages. Thirty-four patients (79%) had white matter lesions. These lesions were hyperintense on T2-weighted images, were isointense on T1-weighted images, and showed no mass effect or contrast enhancement in 31 patients; in three patients, T1-prolongation was observed (one with significant mass effect). None of the lesions evolved into a glioma. The most common locations were the cerebellum (49%), brainstem (22%), and internal capsule (19%). Nineteen patients had white matter lesions and follow-up studies. Lesions decreased in size or number in seven patients (average age, 13 years), showed no change in three (average age, 12 years), increased in size or number in four (average age, 5 years), and showed a mixed pattern (increased/decreased size/number) in four (average age, 7 years). White matter lesions in neurofibromatosis type 1 frequently increase in size or number early in childhood; this did not indicate neoplasia in our study. The lesions tend to resolve with increasing age. Lesion progression in a child more than 10 years old warrants close follow-up to rule out a neoplasm.

    View details for Web of Science ID A1992JA20000037

    View details for PubMedID 1609692

  • INVASIVE ASPERGILLOSIS IN NEONATES - REPORT OF 5 CASES AND LITERATURE-REVIEW PEDIATRIC INFECTIOUS DISEASE JOURNAL Rowen, J. L., Correa, A. G., Sokol, D. M., Hawkins, H. K., Levy, M. L., Edwards, M. S. 1992; 11 (7): 576-582

    View details for Web of Science ID A1992JC74600013

    View details for PubMedID 1528649

  • INVOLVEMENT OF MULTIPLE CHROMOSOME 17P LOCI IN MEDULLOBLASTOMA TUMORIGENESIS AMERICAN JOURNAL OF HUMAN GENETICS Cogen, P. H., DANESHVAR, L., Metzger, A. K., Duyk, G., Edwards, M. S., Sheffield, V. C. 1992; 50 (3): 584-589

    Abstract

    Loss of heterozygosity for sequences located on chromosome 17p in several tumor types is often associated with mutations in the tumor suppressor gene p53. We previously showed consistent deletion of chromosome 17p12-13.1 in medulloblastoma, a common childhood brain tumor. Using denaturing gradient gel electrophoresis and direct sequencing, we have detected p53 mutations in only two of 20 medulloblastoma specimens. Moreover, additional RFLP studies of these 20 specimens showed loss of heterozygosity at a more distal and distinct site, 17p13.3. Deletion of 17p almost invariably signified a negative prognosis. Our results suggest that p53 mutations may contribute to the pathogenesis of medulloblastoma in relatively few cases. The consistent deletion of other discrete loci on 17p suggests that additional or alternative tumor suppressor genes may contribute to the tumor's phenotype.

    View details for Web of Science ID A1992HH97400018

    View details for PubMedID 1347196

  • APPLICATIONS OF NEUROIMAGING IN HYDROCEPHALUS PEDIATRIC NEUROSURGERY Barkovich, A. J., Edwards, M. S. 1992; 18 (2): 65-83

    Abstract

    Hydrocephalus is a common problem in pediatric neurological and neurosurgical practices. In this manuscript, the common imaging appearances of hydrocephalus are discussed in relation to the underlying causes of the hydrocephalus. Moreover, specific findings seen on magnetic resonance imaging (MR) examinations are discussed and contrasted with those on computed x-ray tomography (CT) and ultrasound. Finally the imaging findings associated with treatment of hydrocephalus are discussed. In particular, analysis of shunt function, the diagnosis of shunt failure, and the complications of shunting are stressed.

    View details for Web of Science ID A1992JV55500003

    View details for PubMedID 1419845

  • NEUROCUTANEOUS MELANOSIS IN ASSOCIATION WITH THE DANDY-WALKER COMPLEX PEDIATRIC DERMATOLOGY KADONAGA, J. N., Barkovich, A. J., Edwards, M. S., Frieden, I. J. 1992; 9 (1): 37-43

    Abstract

    An infant had a giant congenital nevus, neurocutaneous melanosis (NCM), and a Dandy-Walker malformation of the brain. The diagnosis of NCM was suspected at 6 weeks of age when macrocephaly was noted, resulting in the discovery of hydrocephalus and a Dandy-Walker malformation. Serial magnetic resonance imaging scans demonstrated so-called T1 shortening in the pia or subarachnoid spaces surrounding the cerebellar vermis and in the temporal lobes anterior to the temporal horns. Eventually, a biopsy-proved melanoma developed in the anterior temporal lobe, in an area previously noted to have T1 shortening. Since meningeal cells have been shown experimentally to play a critical role in cerebellar development, we hypothesize that the association of NCM with a Dandy-Walker malformation may be due to meningeal melanosis disrupting the normal development of the cerebellum and fourth ventricle.

    View details for Web of Science ID A1992HJ83100007

    View details for PubMedID 1574474

  • HYPERFRACTIONATED RADIATION-THERAPY FOR GLIOMAS OF THE BRAIN-STEM IN CHILDREN AND IN ADULTS INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Shrieve, D. C., Wara, W. M., Edwards, M. S., Sneed, P. K., Prados, M. D., Cogen, P. H., Larson, D. A., Levin, V. A. 1992; 24 (4): 599-610

    Abstract

    Between February 1984 and September 1990, 60 patients with brainstem gliomas were treated with hyperfractionated radiotherapy in the Department of Radiation Oncology at the University of California, San Francisco. Forty-one children (< or = 18 years) and 19 adults were treated with 100 cGy twice daily with 4-8 hr between doses. Thirty-one patients (21 children and 10 adults) received total doses of 66-72 Gy and 29 patients (20 children and nine adults) received 74-78 Gy. Median follow-up was 208 weeks for all patients (214 weeks for children, 157 weeks for adults). Twenty-three patients (14 children and nine adults) were alive at the time of analysis, surviving 59-359 weeks following treatment. Median actuarial survival was 73.6 weeks overall (72 weeks for children, 190 weeks for adults; p = 0.43). Survival at 12 and 24 months was 65% and 38%, respectively (63% and 32%, for children; 68% and 53% for adults). All patients had pretreatment magnetic resonance imaging by which tumors were classified as either focal or diffuse. No significant pretreatment prognostic factors for adults were identified. In children, significant favorable prognostic factors on univariate analysis were older age (p = 0.001), tumor location in thalamus or midbrain (p = 0.002), focal appearance on MRI scan (p < 0.001) and duration of symptoms > 2 months prior to treatment (p < 0.001). Thirty-five patients had tumor biopsies, leading to a diagnosis in 33 (22 children and 11 adults). Children with moderately anaplastic astrocytomas survived significantly longer than those with glioblastoma multiforme or unbiopsied tumors (p < 0.001). Only duration of symptoms > 2 months remained significant as a favorable prognostic indicator for children on multivariate analysis (p < 0.001). Survival was not significantly different for patients receiving < or = 72 Gy and those receiving > 72 Gy (p = 0.18). No subgroup of patients showed significantly better survival with the higher dose. These findings indicate that hyperfractionated radiotherapy is effective treatment for adults and a subgroup of better prognosis children with brainstem gliomas. There is a subgroup of pediatric patients with extremely poor prognosis for whom even this aggressive treatment does little to extend survival. We conclude that there is no benefit to increasing total dose above 72 Gy for any of the groups analyzed.

    View details for Web of Science ID A1992JY08900003

    View details for PubMedID 1429081

  • METASTATIC JUVENILE PILOCYTIC ASTROCYTOMA - CASE-REPORT JOURNAL OF NEUROSURGERY OBANA, W. G., Cogen, P. H., Davis, R. L., Edwards, M. S. 1991; 75 (6): 972-975

    Abstract

    The authors report the case of a metastatic juvenile pilocytic astrocytoma of the hypothalamic region in a 10-year-old boy. Eight years after craniotomy and radiation therapy, the tumor spread via cerebrospinal fluid pathways to the left cerebellar tonsil and the lumbosacral region. Histological evaluation of both the original hypothalamic and the new lumbosacral masses showed features of a slow-growing juvenile pilocytic astrocytoma with no evidence of malignant transformation. The clinical implications and possible mechanisms of metastatic spread are discussed.

    View details for Web of Science ID A1991GQ94600021

    View details for PubMedID 1941128

  • NEUROLEPTIC MALIGNANT SYNDROME PEDIATRICS Edwards, M. S. 1991; 88 (5): 1074-1074

    View details for Web of Science ID A1991GM93400036

    View details for PubMedID 1796971

  • IDENTIFICATION OF A GERM-LINE MUTATION IN THE P53 GENE IN A PATIENT WITH AN INTRACRANIAL EPENDYMOMA PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Metzger, A. K., Sheffield, V. C., Duyk, G., DANESHVAR, L., Edwards, M. S., Cogen, P. H. 1991; 88 (17): 7825-7829

    Abstract

    We detected a germ-line mutation of the p53 gene in a patient with a malignant ependymoma of the posterior fossa. This mutation, which was found at codon 242, resulted in an amino acid substitution in a highly conserved site of exon 7 of the p53 gene; the same mutation was found in both the germ-line and the tumor tissue. This is the most common region of previously described somatic p53 mutations in tumor specimens and of the germ-line p53 mutations in patients with the Li-Fraumeni cancer syndrome. Evaluation of the patient's family revealed several direct maternal and paternal relatives who had died at a young age from different types of cancer. The association of a germ-line p53 mutation with an intracranial malignancy and a strong family history of cancer suggests that p53 gene mutations predispose a person to malignancy and, like retinoblastoma mutations, may be inherited.

    View details for Web of Science ID A1991GC99200078

    View details for PubMedID 1679237

  • ULTRASOUND-GUIDED ASPIRATION OF A NEONATAL BRAIN-ABSCESS CHILDS NERVOUS SYSTEM OBANA, W. G., Cogen, P. H., Callen, P. W., Edwards, M. S. 1991; 7 (5): 272-274

    Abstract

    The authors successfully treated a Serratia marcescens brain abscess in the right parieto-occipital region of a newborn infant born at 27 weeks' gestation and weighing 800 g. Bedside ultrasound-guided aspiration techniques and local anesthesia were used to treat the abscess.

    View details for Web of Science ID A1991GF16200007

    View details for PubMedID 1933928

  • MANAGEMENT OF CHIASMAL AND HYPOTHALAMIC GLIOMAS OF INFANCY AND CHILDHOOD WITH CHEMOTHERAPY JOURNAL OF NEUROSURGERY Petronio, J., Edwards, M. S., Prados, M., FREYBERGER, S., Rabbitt, J., Silver, P., Levin, V. A. 1991; 74 (5): 701-708

    Abstract

    Between March, 1983, and February, 1989, 19 infants or children with chiasmal/hypothalamic gliomas were treated with chemotherapy after either surgical or radiological diagnosis. The patients ranged in age from 15 weeks to 15.6 years (median 3.2 years) at the start of therapy. Twelve patients were treated immediately after diagnosis because of progressive symptoms, and seven received chemotherapy after either radiographic progression or clinical deterioration, including progressive visual loss or intracranial hypertension. Based on biopsy results, seven of these tumors were classified as juvenile pilocytic astrocytomas, two as astrocytomas, two as highly anaplastic astrocytomas, and one as a subependymal giant-cell astrocytoma. There was associated neurofibromatosis in four patients. The two initial patients were treated with either actinomycin D and vincristine or 5-fluorouracil, hydroxyurea, and 6-thioguanine. The remaining patients received nitrosourea-based therapy; 15 evaluable patients were treated with a five-drug regimen that included 6-thioguanine, procarbazine, dibromodulcitol, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), and vincristine and one received 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and 5-fluorouracil. Fifteen of the 18 evaluable patients initially managed with chemotherapy either responded to therapy or their condition stabilized. Median time to tumor progression has not been reached at a median follow-up period of 79 weeks (range 6.6 to 303 weeks), and no tumor-related death has occurred with a median follow-up period of 79 weeks (range 18 to 322 weeks) from the initiation of therapy. The four patients who failed therapy or whose disease progressed after chemotherapy were treated satisfactorily with radiation therapy. Initial improvement or stabilization of visual function was obtained in 16 patients. Endocrine function remained stable in all patients during treatment, although three patients required pharmacological treatment for endocrinopathy that was present at diagnosis. These preliminary results suggest that nitrosourea-based cytotoxic regimens are useful for the initial treatment of children with chiasmal/hypothalamic gliomas, and allow potentially harmful radiation therapy to be deferred until progression of disease.

    View details for Web of Science ID A1991FH45700002

    View details for PubMedID 1901597

  • Pediatric brain tumors. Current problems in pediatrics Warnick, R. E., Edwards, M. S. 1991; 21 (4): 129-173

    View details for PubMedID 1860343

  • HYPERFRACTIONATED IRRADIATION FOR ADULTS WITH BRAIN-STEM GLIOMAS INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Linstadt, D. E., Edwards, M. S., Prados, M., Larson, D. A., Wara, W. M. 1991; 20 (4): 757-760

    Abstract

    Hyperfractionated irradiation appears to have improved survival for pediatric patients with brainstem gliomas. However, the efficacy and safety of this technique are less well established for adults with brainstem tumors. In 1984 the UCSF Department of Radiation Oncology began treating adults with brainstem gliomas using 100 cGy fractions given twice daily to total doses ranging between 6600-7800 cGy (median dose 7200 cGy). By the end of 1989, a total of 14 patients had been irradiated with follow-up times for surviving patients ranging between 4-69 months (median follow-up 33 months). Tumor histologies included five moderately anaplastic astrocytomas, one highly anaplastic astrocytoma, and eight which were unbiopsied. At the time of this analysis, six patients had failed locally, with five dying as a result of recurrent tumor. There were no deaths caused by complications or intercurrent illness. The 3-year actuarial survival rate was 59%, with a corresponding 3-year actuarial local control rate of 48%. The projected median survival was in excess of 5 years, whereas the actuarial median time to progression was 31 months (134 weeks). The treatments were well tolerated: the mean pretreatment Karnofsky Performance Status was 74% (range 60-90%); at the end of treatment the mean KPS was 78% (range 60-100%). In terms of neurologic status, six patients improved by the end of treatment, seven were stable, and one experienced only minor deterioration without change in KPS. There were no significant long-term complications (specifically, no instances of either radiation brain necrosis or myelitis). Seven patients required prolonged steroid administration after completing radiotherapy; six of these eventually recurred locally. These results appear to be substantially better than those achieved using conventional radiotherapy regimens, and suggest that this technique merits further investigation.

    View details for Web of Science ID A1991FC80600016

    View details for PubMedID 2004952

  • LOW-DOSE CRANIOSPINAL RADIATION-THERAPY FOR MEDULLOBLASTOMA INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Halberg, F. E., Wara, W. M., FIPPIN, L. F., Edwards, M. S., Levin, V. A., Davis, R. L., PRADOS, M. B., Wilson, C. B. 1991; 20 (4): 651-654

    Abstract

    At the University of California, San Francisco, 65 children with medulloblastoma of the posterior fossa were treated postoperatively with craniospinal irradiation; the dose to the posterior fossa was 54 Gy. The 26 children initially treated had only radiation therapy, receiving 30 to 40 Gy to the spine and 40 to 50 Gy to the brain. Subsequently, 39 children were treated with low-dose craniospinal irradiation and chemotherapy; 24 to 30 Gy was directed to the whole brain and 24 to 26 Gy to the spinal axis. Chemotherapy generally consisted of procarbazine just before, and hydroxyurea during, radiation therapy. Poor-risk and good-risk patients (defined by tumor resection less than 75% or greater than 75%, positive or negative myelogram, positive or negative cerebrospinal fluid analysis, age less than or greater than 2 years, respectively) were evenly distributed between the low-dose and high-dose craniospinal radiation therapy groups. Median follow-up was 51 months (range, 24 to 228 months). Kaplan-Meier actuarial survival for all patients was 73% at 5 years, 70% at 10 years. Freedom from disease progression was 68% at 5 years, 65% at 10 years. Whereas poor-risk patients treated with low-dose craniospinal irradiation and chemotherapy had a 5-year survival of 58% and a 5-year freedom from disease progression of 39%, those figures in the comparable good-risk patients were 83% and 77%, respectively. For both good-risk and poor-risk patients, the posterior fossa was the primary site of recurrence. Tumors recurred in the frontal region, probably under blocks, in three patients receiving low-dose irradiation and in two receiving the higher dose. Reducing the dose of whole-brain and spinal irradiation and giving chemotherapy did not result in a higher rate of recurrence in the brain or spinal cord. Intellectual and social function appeared better in patients receiving the lower dose. We did not study whether chemotherapy benefitted good-risk patients. Craniospinal axis irradiation at a lower dose than conventionally used does not compromise local control or survival in patients with medulloblastoma, and may reduce toxicity.

    View details for Web of Science ID A1991FC80600001

    View details for PubMedID 2004939

  • BILATERAL RETINAL HAMARTOMAS IN NEUROFIBROMATOSIS TYPE-2 BRITISH JOURNAL OF OPHTHALMOLOGY Good, W. V., Brodsky, M. C., Edwards, M. S., Hoyt, W. F. 1991; 75 (3): 190-190

    Abstract

    We report a case of bilateral retinal hamartomas in a child with neurofibromatosis type 2. This unique case demonstrates that a diversity of retinal changes can occur in this disease.

    View details for Web of Science ID A1991EZ07900020

    View details for PubMedID 1901496

  • INTRACRANIAL ARACHNOID CYSTS IN CHILDREN - A COMPARISON OF THE EFFECTS OF FENESTRATION AND SHUNTING JOURNAL OF NEUROSURGERY Ciricillo, S. F., Cogen, P. H., Harsh, G. R., Edwards, M. S. 1991; 74 (2): 230-235

    Abstract

    The best operative intervention for children with arachnoid cysts remains the subject of controversy. Recent reports stress that craniotomy for cyst fenestration is associated with a low incidence of morbidity and mortality and may leave the child shunt-independent. The cases of 40 pediatric patients with arachnoid cysts treated between 1978 and 1989 are reported. Five children with mild symptoms and small cysts that remained stable on follow-up studies have not required surgical intervention. Of 15 patients with cysts initially treated by fenestration, 10 (67%) showed no clinical or radiographic improvement postoperatively and have undergone cyst-peritoneal (eight patients) or ventriculoperitoneal (VP) shunting (one patient), or revision of a VP shunt placed for hydrocephalus before cyst fenestration (one patient). Two other patients with existing VP shunts required no further procedures. Thus, only three (20%) of 15 patients initially treated by fenestration remain shunt-independent after a median follow-up period of 8 years. The 20 other patients were initially treated by cysts shunting and all improved postoperatively; shunt revision has been necessary in six (30%) of these 20 patients because of cysts recurrence. Cyst location influenced the success of shunt treatment; none of the seven middle cranial fossa cysts treated by shunting have required revision, but results with cysts in other locations were less favorable. In all locations, though, shunting was more successful than fenestration. It is concluded that cyst-peritoneal or cyst-VP shunting is the procedure of choice for arachnoid cysts in most locations, including those in the middle cranial fossa.

    View details for Web of Science ID A1991EU62200011

    View details for PubMedID 1988593

  • Magnetic resonance analysis of suprasellar tumors of childhood. Pediatric neurosurgery Kollias, S. S., Barkovich, A. J., Edwards, M. S. 1991; 17 (6): 284-303

    Abstract

    A retrospective analysis of the magnetic resonance (MR) images in 53 pediatric patients with pathologically proven suprasellar tumors was performed, in an attempt to identify the characteristic MR features of these tumors and assess the capability of MR to predict a histologic differentiation. The tumors analyzed included 29 astrocytomas, 11 craniopharyngiomas, 4 germinomas, 3 pituitary adenomas with suprasellar extension, 2 teratomas, 1 spindle cell tumor, 1 primitive neuroectodermal tumor, 1 arachnoid cyst and 1 chordoma of the clivus with suprasellar extension. Thirty patients received intravenous Gd-DTPA as part of their MR exam. Certain MR features, while not pathognomonic, are quite helpful in the differentiation of craniopharyngiomas from chiasmatic/hypothalamic astrocytomas. Presence of a high signal intensity component on T1-weighted images, cyst formation with macrocystic predominance, irregular, heterogeneous solid portion, and smooth ring cyst wall enhancement represent the key characteristics of craniopharyngiomas. Solid predominance with microcysts, long T1 and T2 relaxation times, intense enhancement after contrast administration and extension along the posterior optic pathways are the typical MR findings of chiasmatic/hypothalamic astrocytomas. Presence of diabetes insipidus in correlation with the MR findings of a well-marginated, round or lobular tumor with prolonged T1 and T2 relaxation times, which enhances strongly after Gd-DTPA administration may be the clue in the diagnosis of suprasellar germinomas. Teratomas can be separated from other pediatric suprasellar neoplasms on the basis of internal heterogeneity with presence of fat, calcium and various soft tissue densities. Tumors invading the suprasellar cistern by extension are easily differentiated by identification of the primary site of origin. The above features, while not pathognomonic, are quite helpful in making a specific diagnosis.

    View details for PubMedID 1668642

  • CONGENITAL NASAL MASSES - CT AND MR IMAGING FEATURES IN 16 CASES AMERICAN JOURNAL OF NEURORADIOLOGY Barkovich, A. J., VANDERMARCK, P., Edwards, M. S., Cogen, P. H. 1991; 12 (1): 105-116

    Abstract

    The imaging studies of 16 children with pathologically proved nasal encephaloceles (eight), nasal dermal sinuses/nasal dermoids (seven), and nasal cerebral heterotopias, more commonly known as nasal gliomas (one), were retrospectively reviewed and compared with normal control subjects to define the normal anatomy and analyze deformities caused by these lesions. Nasal encephaloceles were always identified as complex masses of mixed soft tissue and CSF intensity that were contiguous with intracranial structures. The nasal glioma appeared as a mixed-intensity mass that, on the basis of the CT scan, appeared to be continuous with intracranial structures. Nasal dermal sinuses could only be identified as they coursed through the skin and subcutaneous soft tissue. They could not be identified when intraosseous. Moreover, on CT and, particularly, on MR, a number of potential diagnostic pitfalls were encountered. The most important of these was the normal fat deposition that occurs within bone during normal maturation and during aeration of the frontal sinuses and nasal bones. These fatty changes can easily be mistaken for fatty tumors if they are not recognized as normal anatomic changes. Interestingly, the classic plain film findings for congenital nasal masses were present only in the encephaloceles and nasal glioma; dermoids and dermal sinuses showed none of the classic plain film findings. In the six patients who had both CT and MR, the masses were easily identified and characterized by each imaging method. Congenital nasal masses are well characterized by both CT and MR. It is important to understand the normal changes in the anatomy of the nasofrontal region in the pediatric age group to avoid false-positive diagnoses in this region.

    View details for Web of Science ID A1991EN93800022

    View details for PubMedID 1903239

  • MR APPEARANCE OF POSTOPERATIVE FOREIGN-BODY GRANULOMA - CASE-REPORT WITH PATHOLOGICAL CONFIRMATION AMERICAN JOURNAL OF NEURORADIOLOGY DEMARCO, J. K., McDermott, M. W., Dillon, W. P., Bollen, A., Edwards, M. S. 1991; 12 (1): 190-192

    View details for Web of Science ID A1991EN93800043

    View details for PubMedID 1899512

  • ANTIMIGRAINE TREATMENT FOR SLIT VENTRICLE SYNDROME NEUROSURGERY OBANA, W. G., Raskin, N. H., Cogen, P. H., Szymanski, J. A., Edwards, M. S. 1990; 27 (5): 760-763

    Abstract

    Slit ventricle syndrome is characterized by chronic or recurring headaches associated with subnormal ventricular volume in patients who have undergone shunt treatment for hydrocephalus. There appear to be at least three pathophysiological mechanisms that cause this syndrome: 1) intermittent shunt malfunction; 2) intracranial hypotension; and 3) paroxysms of increased intracranial pressure in the presence of normal shunt function. To treat seven patients with slit ventricle syndrome caused by paroxysms of elevated intracranial pressure, we successfully used antimigraine therapy rather than standard calvarial expansion procedures. None of these patients has required shunt revision or calvarial expansion during a mean follow-up period of 2 years. The symptoms of slit ventricle syndrome may be a form of "acquired" migraine in shunt patients. We suggest that, in clinically stable patients with normal shunt function, treatment against migraine may stabilize symptoms resulting from paroxysms of increased intracranial pressure. Such treatment may prevent unnecessary shunt revisions and/or calvarial expansion procedures.

    View details for Web of Science ID A1990EE94800014

    View details for PubMedID 2259406

  • DELETION MAPPING OF THE MEDULLOBLASTOMA LOCUS ON CHROMOSOME-17P GENOMICS Cogen, P. H., DANESHVAR, L., Metzger, A. K., Edwards, M. S. 1990; 8 (2): 279-285

    Abstract

    Isochromosome 17q has previously been observed consistently in cytogenetic studies of medulloblastoma, the most common posterior fossa neoplasm in children. We performed a restriction fragment length polymorphism (RFLP) investigation of medulloblastoma which showed a loss of chromosome 17p sequences in 45% of these tumors. This finding was predictive of a poor clinical response to treatment. A contiguous panel of markers permitted mapping of the deletion to 17p12-p13.1, the same chromosomal region for which loss of alleles has been shown in tumor specimens from patients with colon cancer, and the same region to which the p53 gene has been mapped. This suggests that medulloblastoma is associated with a recessive oncogene on chromosome 17p that may be involved in the genesis of several embryologically unrelated neoplasms and that the absence of this gene in tumor tissue has prognostic significance.

    View details for Web of Science ID A1990EA91200013

    View details for PubMedID 1979050

  • SERIAL ULTRASONOGRAPHIC EVALUATION OF NEONATAL VEIN OF GALEN MALFORMATIONS TO ASSESS THE EFFICACY OF INTERVENTIONAL NEURORADIOLOGICAL PROCEDURES NEUROSURGERY Ciricillo, S. F., Schmidt, K. G., Silverman, N. H., Hieshima, G. B., Higashida, R. T., Halbach, V. V., Edwards, M. S. 1990; 27 (4): 544-548

    Abstract

    Two-dimensional echocardiography complemented with color-flow imaging and pulsed Doppler ultrasound was used to evaluate one fetus and five neonates with a vein of Galen malformation who had severe high-output congestive heart failure and cranial bruits at birth. Intracranial blood flow through the vein of Galen malformations, cardiac status, and direction of aortic blood flow were assessed before and after staged interventional neuroradiological treatment with transarterial and transvenous embolization procedures. Color-flow imaging in each infant displayed the major vascular anatomy including feeding vessels and the patterns of filling of the vein of Galen malformations. Pulsed Doppler ultrasound performed on the descending aorta above the diaphragm showed the degree of diastolic flow reversal indicative of runoff into the vein of Galen malformations. A reduction in blood flow through the vein of Galen malformation was seen on color-flow imaging in four patients treated successfully by embolic procedures. The ratio of diastolic retrograde flow velocity in the descending aorta to systolic antegrade velocity decreased from 0.51 +/- 0.15 (mean +/- standard deviation) to 0.15 +/- 0.20 (P less than 0.05). Color-flow imaging and pulsed Doppler ultrasonography provided anatomical and pathophysiological information regarding cardiac hemodynamics and intracranial blood flow; with the patient's clinical status, these methods provided a reliable, noninvasive means to evaluate the effectiveness of therapy and the need for further treatment in neonates with vein of Galen malformations.

    View details for Web of Science ID A1990DZ55100007

    View details for PubMedID 2234356

  • INTERVENTIONAL NEURORADIOLOGICAL MANAGEMENT OF VEIN OF GALEN MALFORMATIONS IN THE NEONATE NEUROSURGERY Ciricillo, S. F., Edwards, M. S., Schmidt, K. G., Hieshima, G. B., Silverman, N. H., Higashida, R. T., Halbach, V. V. 1990; 27 (1): 22-28

    Abstract

    Since 1978, the authors have seen 14 neonates with vein of Galen malformations who were born with severe congestive heart failure. The 5 infants treated before 1983 underwent craniotomy and clipping of feeding vessels; all died in the perioperative period. Since 1983, 8 neonates have been treated with combined arterial and venous interventional neuroradiological techniques; 6 infants survived. Two-dimensional echocardiography, color Doppler flow imaging, and pulsed Doppler ultrasound were used to assess blood flow within the malformation before and after staged transluminal embolic procedures were performed. The results of the diagnostic studies and the clinical status of the infants were used to evaluate the success of embolic therapy and the need for further neuroradiological intervention.

    View details for Web of Science ID A1990DL50500003

    View details for PubMedID 2198486

  • MR IMAGING OF PINEAL TUMORS AMERICAN JOURNAL OF ROENTGENOLOGY Tien, R. D., Barkovich, A. J., Edwards, M. S. 1990; 155 (1): 143-151

    Abstract

    MR images of pineal region tumors were analyzed in 26 patients with histologically proved tumors: seven germ-cell tumors, six astrocytomas, five teratomas, three pineoblastomas, two meningiomas, one dermoid, one epidermoid, and one metastasis. In an attempt to identify specific MR characteristics of these lesions, Gd-DTPA was administered to six patients. CSF and blood serum were assayed for alpha-fetoprotein (AFP) and human chorionic gonadotropin-beta subunit (HCG-beta) in 18 patients. MR findings were correlated with age, sex, the presence of biochemical tumor markers, and surgical outcome. We found that the most important factors in the determination of tumor type were the patient's age and the tumor markers. Increased levels of both HCG-beta and AFP were specific for patients with malignant teratomas and undifferentiated germ-cell tumors. HCG-beta alone was elevated in the patient with choriocarcinoma; only AFP was elevated in the patient with an endodermal sinus tumor. Tumor markers were not present in other patients in this series. The tumor size and the presence of fat were also helpful in determining tumor type. Hemorrhage was rare, seen only in the patient with a choriocarcinoma. Gd-DTPA did not enhance diagnostic specificity but aided in the detection of tumor seeding through CSF. We conclude that, although MR is sensitive in the detection of pineal region tumors and provides superb anatomic detail, MR signal characteristics are usually nonspecific. Correlation with the patient's age and the tumor markers significantly improves diagnostic accuracy.

    View details for Web of Science ID A1990DK48700031

    View details for PubMedID 2162137

  • TRANSFEMORAL VENOUS EMBOLIZATION OF VEIN OF GALEN MALFORMATIONS AMERICAN JOURNAL OF NEURORADIOLOGY Dowd, C. F., Halbach, V. V., Barnwell, S. L., Higashida, R. T., Edwards, M. S., Hieshima, G. B. 1990; 11 (4): 643-648

    Abstract

    Three infants with vein of Galen malformations, all presenting with congestive heart failure, underwent a total of five embolization procedures that employed a percutaneous transfemoral venous approach to catheterize the vein of Galen. In one instance, direct retrograde catheterization of feeding arterial pedicles to the vein of Galen and embolization of the fistulous connections was achieved via this route. The indications for transfemoral venous treatment included persistent symptoms despite transarterial and transtorcular embolization in one patient, an unsuccessful transarterial embolization attempt (complicated by catheter fracture) in another, and the inadvisability of transarterial embolization because of an excessive number of feeding arteries in a third. Complete obliteration of the malformation was achieved in one patient and significant flow reduction in the other two. Vein of Galen perforation with the catheter tip complicated one procedure. All three patients were stable after clinical follow-ups (9-12 months). The transvenous route to the vein of Galen can be undertaken from a transfemoral approach, obviating surgical exposure of the torcular Herophili. In addition, we introduce the concept of direct retrograde catheterization of the feeding arteries to the vein of Galen malformation by a transfemoral venous approach, a procedure that has not been reported previously.

    View details for Web of Science ID A1990DL90400006

    View details for PubMedID 2114741

  • BLADDER FUNCTION IN PATIENTS WITH LIPOMYELOMENINGOCELE JOURNAL OF UROLOGY Foster, L. S., Kogan, B. A., Cogen, P. H., Edwards, M. S. 1990; 143 (5): 984-986

    Abstract

    We evaluated preoperative and postoperative bladder function in 31 consecutive patients who underwent definitive operative correction of lipomyelomeningocele. Of 12 patients less than 1.5 years old at operation, bladder function was normal preoperatively and postoperatively in 5 (42%) and normalized postoperatively in 4 (33%). In 5 patients (42%) abnormal urodynamic findings were the only sign of neurological abnormality. Of the 19 patients older than 1.5 years at operation bladder function was normal preoperatively and postoperatively in only 4 (21%), and normalized postoperatively in none. We conclude that the majority of patients with lipomyelomeningocele have bladder dysfunction, and that in some cases this dysfunction can be prevented and/or reversed by early neurosurgical intervention. Urodynamic assessment is helpful as part of the neurological evaluation and in directing patient care.

    View details for Web of Science ID A1990DB32000028

    View details for PubMedID 2329617

  • MANAGEMENT OF CHILDHOOD CEREBELLAR ASTROCYTOMA INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Larson, D. A., Wara, W. M., Edwards, M. S. 1990; 18 (4): 971-973

    View details for Web of Science ID A1990DB10800035

    View details for PubMedID 2323983

  • CRYPTIC VASCULAR MALFORMATIONS OF THE SPINAL-CORD - DIAGNOSIS BY MAGNETIC-RESONANCE-IMAGING AND OUTCOME OF SURGERY JOURNAL OF NEUROSURGERY Barnwell, S. L., Dowd, C. F., Davis, R. L., Edwards, M. S., Gutin, P. H., Wilson, C. B. 1990; 72 (3): 403-407

    Abstract

    The cases of seven patients with intramedullary, cryptic vascular malformations of the spinal cord are reported. In all patients, the clinical course was progressive; a Brown-Séquard syndrome was the most common presenting symptom complex. Magnetic resonance (MR) imaging was performed in all patients. The pattern seen most often was a focus of high signal (on both T1- and T2-weighted MR images) surrounded by a larger zone of low signal (best seen on T2-weighted images), and was remarkably similar for all patients. Six patients underwent surgical exploration; removal of the lesions halted the progression of symptoms in five patients, and one patient had worsened sensory function after surgery. Motor function did not decrease postoperatively in any patient. The one patient who refused surgery has continued to decline neurologically. Histopathological examination of surgical specimens showed a cavernous malformation in one patient, a venous malformation in one, venous varices in two, and organizing hematomas in two; these findings are markedly different from those in previously reported cases of cryptic vascular malformations.

    View details for Web of Science ID A1990CP70900007

    View details for PubMedID 2303875

  • ANEURYSMS OF THE PETROUS PORTION OF THE INTERNAL CAROTID-ARTERY - RESULTS OF TREATMENT WITH ENDOVASCULAR OR SURGICAL OCCLUSION AMERICAN JOURNAL OF NEURORADIOLOGY Halbach, V. V., Higashida, R. T., Hieshima, G. B., Dowd, C. F., Barnwell, S. L., Edwards, M. S., Melicharek, M. 1990; 11 (2): 253-257

    Abstract

    Seven patients with symptomatic aneurysms involving the petrous segment of the internal carotid artery were treated by endovascular techniques (six patients) or surgical ligation (one patient). Patients' ages at the time of treatment ranged from 7 to 62 years (mean, 30 years). The presenting symptoms were pain (seven patients), eighth nerve dysfunction (three patients), seventh nerve dysfunction (one patient), fifth nerve dysfunction (two patients), and bruit (one patient). Two patients, ages 7 and 19, respectively, presented with giant, partially thrombosed petrous aneurysms and had hemiatrophy of the body ipsilateral to the side of the aneurysm. Only one patient had a history of trauma; aneurysms in the remaining patients were presumed to be congenital in origin. In one patient with a saccular aneurysm, a balloon could be navigated into the aneurysm, obliterating it but preserving the parent artery. The remaining six patients had fusiform aneurysms with intraluminal thrombus and underwent proximal occlusion (four patients) or trapping procedure (two patients). In all patients, symptoms were alleviated after thrombosis of the aneurysm. The only complication was a transient visual loss in a hypercoagulable patient, occurring after carotid occlusion. Petrous carotid aneurysms can produce a wide clinical spectrum of signs and symptoms in younger patients; these aneurysms frequently are fusiform and contain chronic thrombus. They can be treated effectively by endovascular or surgical occlusive procedures.

    View details for Web of Science ID A1990CQ31600006

    View details for PubMedID 2107708

  • MANAGEMENT OF HYPOTHALAMIC GLIOMAS IN CHILDREN - AN ANALYSIS OF 33 CASES NEUROSURGERY Rodriguez, L. A., Edwards, M. S., Levin, V. A. 1990; 26 (2): 242-247

    Abstract

    The cases of 33 children with hypothalamic-chiasmatic gliomas are reviewed. Radiation therapy produced clinical or radiographic improvement in 11 (46%) of 24 patients. Progression was documented in 18 patients (54%). Overall, the median time to tumor progression was 60 months; it was 70 months in patients who received radiation therapy and 30 months in those who did not (P less than 0.05). Chemotherapy, either given initially or at the time of progression, caused the tumor to respond or to stabilize in 10 patients. Partial resection of the tumor led to improvement in 3 of 12 patients, obviating the need for a shunt in 2 of them; there were no deaths and postoperative morbidity was transient and minimal (diabetes insipidus, intraventricular hemorrhage, and left hemiparesis in one patient each). The 5- and 10-year survival probabilities were 93 and 74%, respectively. Patients with neurofibromatosis had a better prognosis.

    View details for Web of Science ID A1990CM11500010

    View details for PubMedID 2308672

  • Histologic evaluation of the coronal sutures in trigonocephaly. journal of craniofacial surgery Ousterhout, D. K., ESKENAZI, L., Golabi, M., Edwards, M. S. 1990; 1 (1): 15-17

    Abstract

    Thirteen cases of trigonocephaly, seven isolated and six syndromic cases, were evaluated by preoperative neurologic and genetic evaluation and by radiographic evaluation (CT scans). All 13 were treated in an identical surgical manner. Specimens from the coronal sutures were obtained during surgery for histologic evaluation. All of the isolated cases, except one, showed normal coronal sutures and had a good-to-excellent result from surgery. All of the syndromic or secondary cases showed an abnormality of the coronal sutures. Four of the six cases had bad results; two required subsequent surgical procedures. It is our opinion that if a coronal suture abnormality is noted on preoperative CT scans or if preoperative evaluation demonstrates an associated syndrome or CNS malformation, the results from surgery must be guarded.

    View details for PubMedID 2088559

  • INTRACEREBRAL ARTERIOVENOUS-FISTULAS ASSOCIATED WITH INTRAPARENCHYMAL VARIX IN CHILDHOOD - CASE-REPORTS NEUROSURGERY Barnwell, S. L., Ciricillo, S. F., Halbach, V. V., Edwards, M. S., Cogen, P. H. 1990; 26 (1): 122-125

    Abstract

    This report describes three children, each of whom developed an unusual malformation consisting of one or more intracerebral arteriovenous fistulas and a large intraparenchymal venous varix. Their clinical symptoms were similar to those produced by aneurysms of the vein of Galen: increasing head circumference, seizures, hemorrhage, and developmental delay. We treated each child with endovascular embolization and/or surgery and obtained complete closure of all fistulas without mortality.

    View details for Web of Science ID A1990CG53300017

    View details for PubMedID 2294462

  • REVISED CLASSIFICATION OF POSTERIOR-FOSSA CYSTS AND CYSTLIKE MALFORMATIONS BASED ON THE RESULTS OF MULTIPLANAR MR IMAGING AMERICAN JOURNAL OF ROENTGENOLOGY Barkovich, A. J., Kjos, B. O., Norman, D., Edwards, M. S. 1989; 153 (6): 1289-1300

    Abstract

    MR and clinical data on 31 patients with posterior fossa CSF collections were analyzed. A clear separation of these patients into classical categories was not possible because of new information obtained from the MR images. We present a new classification of these disorders. The Dandy-Walker malformation, Dandy-Walker variant, and mega-cisterna magna seem to represent a continuum of developmental anomalies of the posterior fossa. A possible embryologic basis for this continuum is suggested. Discrete posterior fossa CSF collections that are clearly separate from the fourth ventricle and vallecula are classified as posterior fossa cysts. Posterior fossa CSF collections that communicate with the fourth ventricle and are associated with cerebellar atrophy are classified as prominent cisterna magna. Both the Dandy-Walker complex and posterior fossa cysts can cause enlargement of the posterior fossa and scalloping of the inner table of the occipital bone. The Dandy-Walker complex presents with seizures, developmental delay, and enlarging head size; it requires CSF diversion when associated with hydrocephalus. Posterior fossa cysts present with symptoms of a posterior fossa mass; they generally require surgical resection. Prominent cisterna magna is a result of degenerative disorders and requires no surgical therapy. This new classification facilitates both diagnosis and therapy of these disorders. MR revealed that disorders previously referred to as the Dandy-Walker malformation, the Dandy-Walker variant, and the mega-cisterna magna actually are not separate entities, but appear to represent steps on a continuum of developmental anomalies of the posterior fossa. Because of this, we suggest a new term, the Dandy-Walker complex, be used to describe this continuum.

    View details for Web of Science ID A1989CA65600034

    View details for PubMedID 2816648

  • Survival and quality of life after interstitial implantation of removable high-activity iodine-125 sources for the treatment of patients with recurrent malignant gliomas. International journal of radiation oncology, biology, physics Leibel, S. A., Gutin, P. H., Wara, W. M., SILVER, P. S., Larson, D. A., Edwards, M. S., Lamb, S. A., Ham, B., Weaver, K. A., Barnett, C. 1989; 17 (6): 1129-1139

    Abstract

    Between January 1980 and January 1988, 95 evaluable patients with recurrent, unifocal, supratentorial malignant gliomas were reirradiated with high-activity iodine-125 sources implanted directly into tumor in afterloaded, removable catheters using computerized tomography-directed stereotaxy. A tumor dose of 5270-15,000 cGy was delivered at a maximum distance of 0.5 cm from the rim of the contrast-enhancing mass seen on CT scans. The median survival for the 50 patients with anaplastic astrocytoma was 81 weeks and for 45 patients with glioblastoma multiforme it was 54 weeks. The 18- and 36-month survival rates for patients with anaplastic astrocytoma were 46% and 28%, respectively; the 18- and 36-month survival rates for patients with glioblastoma multiforme were 22% and 8%, respectively. Because of clinical deterioration, increasing steroid dependency, and increasing mass effect at the implantation site seen on CT scans, necrotic tissue was excised from 47 patients (49%) at craniotomy; in some patients, tumor was mixed with necrotic tissue. The survival of reoperated patients was significantly longer compared with patients who did not undergo this procedure. Serial determination of the Karnofsky Performance Score (KPS) showed that there was no significant deterioration for the group as a whole during the 6 months immediately after implantation. At 18 months, 33 of the patients were alive; KPS ranged between 50 to 90 (mean 79) and 67% were steroid dependent. At 36 months, 18 patients were alive; 17 patients were evaluable with KPS that ranged between 40 to 90 (mean 76) and 53% were steroid dependent. Eleven of the 17 evaluable long-term survivors had a KPS of 80 or higher with a mean of 87. Interstitial brachytherapy may provide long-term survival in selected patients with recurrent malignant gliomas who have been irradiated previously with conventional teletherapy. The quality of life in the majority of long-term survivors appears to be quite satisfactory. Further attempts to control tumor growth using this modality appear to be warranted.

    View details for PubMedID 2557303

  • THE EFFECT OF BROMODEOXYURIDINE AND ULTRAVIOLET-LIGHT ON 9L RAT-BRAIN TUMOR-CELLS RADIATION RESEARCH Raffel, C., Edwards, M. S., Deen, D. F. 1989; 118 (3): 409-419

    Abstract

    Incorporation of the thymidine analog bromodeoxyuridine (BrdUrd) into DNA increases the sensitivity of a cell to uv light. We have examined the effect of uv light on cell killing and alkaline elution profiles in 9L rat brain tumor cells pretreated with BrdUrd. Combination treatment with BrdUrd and uv irradiation produced a dose enhancement ratio of 3.8 at the 10% survival level compared with uv-radiated control cells; cell killing depended on both the time of treatment and the concentration of BrdUrd used for incubation. Sequential treatment caused single-strand breaks and DNA-protein crosslinks in the portion of DNA containing BrdUrd; uv irradiation alone caused very few strand breaks and no DNA-protein crosslinks. Because of the presence of both lesions in cells treated with BrdUrd and uv light, it was possible to calculate crosslinking factors without using a charging X-ray dose to induce strand breaks, the method commonly used with crosslinking drugs. Results of repair studies suggested that single-strand breaks are repaired more rapidly than are DNA-protein crosslinks.

    View details for Web of Science ID A1989U948300003

    View details for PubMedID 2727268

  • HYPERFRACTIONATED RADIATION-THERAPY FOR BRAIN-STEM GLIOMA - A PHASE-I-II TRIAL JOURNAL OF NEUROSURGERY Edwards, M. S., Wara, W. M., Urtasun, R. C., Prados, M., Levin, V. A., Fulton, D., Wilson, C. B., Hannigan, J., Silver, P. 1989; 70 (5): 691-700

    Abstract

    Fifty-three patients (19 adults and 34 children) harboring brain-stem glioma were treated with hyperfractionated radiation therapy (100 cGy twice a day, 5 days/wk, to a total dose of 7200 cGy). For the entire group, the median time to tumor progression (TTP) was 59 weeks (adults 66 weeks, children 44 weeks) and the median survival time was 74 weeks (adults 92 weeks, children 64 weeks). Statistically significant prognostic factors associated with a decrease in TTP and median survival times (adults less than children) were: patient's age, a clinical history of less than 2 months, widespread brain-stem dysfunction, and a diffuse tumor as seen on magnetic resonance imaging. A finding of glioblastoma multiforme at histological analysis was associated with a statistical trend toward poorer survival, but in general tumor histology was not predictive of outcome. No evidence of an increase in acute or delayed radiation toxicity was seen with this fractionation schedule and total dose. This study suggests that hyperfractionation prolongs the TTP and survival time for many patients with brain-stem glioma. However, there remains a group of patients who are only moderately helped by this technique and for whom more aggressive treatment is warranted.

    View details for Web of Science ID A1989U335800005

    View details for PubMedID 2709109

  • PINEOCYTOMAS CANCER DISCLAFANI, A., Hudgins, R. J., Edwards, M. S., Wara, W., Wilson, C. B., Levin, V. A. 1989; 63 (2): 302-304

    Abstract

    Six cases of histologically proven pineocytoma are reported. The diagnosis was established by surgery in five cases and at autopsy in one. All patients received focal radiation therapy (4500 to 5400 cGy). Two patients had local recurrences at 1 and 48 months and subsequently died of tumor. A third patient died of Alzheimer's disease 29 years after the initial presentation. Three patients are alive with no evidence of disease at 21+, 52+, and 84+ months after treatment. Tumor dissemination occurred after a local recurrence in one patient. We found no evidence of recurrence outside the irradiated field unless there was an initial recurrence at the primary tumor site. We recommend postoperative staging for all patients with pineocytoma and focal radiation therapy if local disease alone is found. Craniospinal radiation therapy appears to be justified only if tumor dissemination is documented on staging tests.

    View details for Web of Science ID A1989R775500015

    View details for PubMedID 2910435

  • PROGNOSTIC IMPLICATIONS OF THE PROLIFERATIVE POTENTIAL OF LOW-GRADE ASTROCYTOMAS JOURNAL OF NEUROSURGERY Hoshino, T., Rodriguez, L. A., Cho, K. G., Lee, K. S., Wilson, C. B., Edwards, M. S., Levin, V. A., Davis, R. L. 1988; 69 (6): 839-842

    Abstract

    The proliferative potential of low-grade astrocytomas was estimated in 47 patients. Each patient received an intravenous infusion of bromodeoxyuridine (BUdR), 150 to 200 mg/sq m, at the time of craniotomy to label cells in deoxyribonucleic acid (DNA) synthesis; the percentage of S-phase cells, or BUdR labeling index (LI), of each tumor was determined immunohistochemically. In 29 patients (60%), the tumors had BUdR LI's of less than 1%, indicating a slow growth rate; only three (10%) of these patients died of recurrent tumor during a follow-up period of up to 3 1/2 years. In contrast, of the 18 patients (40%) whose tumors had BUdR LI's of 1% or more, 12 (67%) had a recurrence and nine died during the same follow-up period. These results show that the proliferative potential, as reflected by the BUdR LI, is an important prognostic factor that separates low-grade astrocytomas into two groups and provides a more scientific rationale for selecting treatment for individual patients.

    View details for Web of Science ID A1988R034200005

    View details for PubMedID 3193189

  • SYMPTOMATIC HYDROCEPHALUS - INITIAL FINDINGS IN BRAIN-STEM GLIOMAS NOT DETECTED ON COMPUTED TOMOGRAPHIC SCANS PEDIATRICS Raffel, C., Hudgins, R., Edwards, M. S. 1988; 82 (5): 733-737

    Abstract

    In a retrospective review of 85 patients younger than 18 years of age with a diagnosis of brainstem glioma treated between 1974 and 1987, seven (8.3%) initially had hydrocephalus and no evidence of tumor on CT scans. Intrinsic brain tumors, six in the pons and one in the diencephalon, were discovered later, either on follow-up CT scans or on magnetic resonance images obtained despite persistently normal CT scan findings. The initial radiologic study of choice for children and adolescents with hydrocephalus should be magnetic resonance imaging, including axial and sagittal T1- and T2-weighted images. If a CT scan is obtained first and hydrocephalus but not tumor is found, magnetic resonance image should be obtained to rule out the possible presence of an intrinsic brainstem tumor.

    View details for Web of Science ID A1988Q895300008

    View details for PubMedID 3186352

  • TREATMENT OF EXTRANEURAL METASTATIC MEDULLOBLASTOMA WITH A COMBINATION OF CYCLOPHOSPHAMIDE, ADRIAMYCIN, AND VINCRISTINE NEUROSURGERY Chamberlain, M. C., Silver, P., Edwards, M. S., Levin, V. A. 1988; 23 (4): 476-479

    Abstract

    Seven patients with extraneural metastases from medulloblastoma were treated with a combination of cytoxan, adriamycin, and vincristine (CAV). None of the patients had evidence of active neural axis disease. All patients with bone metastases responded with a reduction in bone pain and improvement on the radionuclide bone scan. One patient presenting with lymph node metastases showed initial reduction in the size of the palpable nodes. In this group, the median time to the development of extraneural metastasis was 18 months from the time of original diagnosis of central nervous system medulloblastoma. The median duration of response to CAV, after extraneural metastasis, was 17 months (4-65 months). Four of seven patients died of disease-related causes, one patient presumed well was lost to follow-up, and two of seven are still without evidence of active disease at 37 and 65 months. The combination of CAV is well tolerated and provides reasonably good palliation for extraneural medulloblastoma.

    View details for Web of Science ID A1988Q561100012

    View details for PubMedID 3200378

  • BROMODEOXYURIDINE - A COMPARISON OF ITS PHOTOSENSITIZING AND RADIOSENSITIZING PROPERTIES JOURNAL OF NEUROSURGERY Raffel, C., Deen, D. F., Edwards, M. S. 1988; 69 (3): 410-415

    Abstract

    The photo- and radiosensitizing properties of bromodeoxyuridine (BUdR) were assessed in vitro using the 9L rat brain tumor cell line. Pretreatment of 9L cells with 10 microM BUdR for 24 hours followed by irradiation with ultraviolet (UV) light resulted in a dose-enhancement ratio of 3.8:1 compared with UV radiation alone. X-radiation of BUdR-pretreated cells produced a dose-enhancement ratio of 1.7:1. Alkaline elution analysis of deoxyribonucleic acid (DNA) from cells treated with BUdR and UV irradiation showed the presence of DNA single-strand breaks and DNA-protein cross-links. Analysis of DNA from cells treated with BUdR and then x-irradiated showed no increase in DNA single-strand breaks compared with cells treated with x-radiation alone; no DNA-protein cross-links could be detected. The possible clinical relevance of these findings is discussed.

    View details for Web of Science ID A1988P874300017

    View details for PubMedID 3404239

  • PROLIFERATIVE CHARACTERISTICS OF INTRACRANIAL AND SPINAL TUMORS OF DEVELOPMENTAL ORIGIN CANCER Cho, K. G., DeArmond, S. J., Barnwell, S., Edwards, M. S., Hoshino, T. 1988; 62 (4): 740-748

    Abstract

    The proliferative potential of 17 intracranial and spinal tumors (six craniopharyngiomas, four chordomas, three mature teratomas, one immature teratoma, one embryonal carcinoma, one choriocarcinoma, and one dermoid tumor) was assessed. The patients received a 30-minute to 60-minute infusion of bromodeoxyuridine (BUdR) (200 mg/m2 intravenously [IV]) at the time of surgery but before a biopsy of the tumor was performed, to label cells in the DNA synthesis phase. The labeling index (LI) was calculated by determining the percentage of BUdR-labeled cells. The mean LI of the squamous epithelial elements of mature teratomas, craniopharyngiomas, and the dermoid tumor were 3.1 +/- 1.2%, 1.9 +/- 0.9%, and 2.9 +/- 1.9%, respectively. As in normal epithelium, the labeled cells were located in the basal layer. These results and the clinical findings suggest that the proliferation kinetics of these tumors are similar to those of normal skin and differ from those of rapidly growing malignant neoplasms. The other tissue elements (i.e., respiratory epithelium and cartilage) also demonstrated "organized" proliferation patterns similar to those of the corresponding normal tissues. An immature teratoma, an embryonal carcinoma, and a choriocarcinoma each had a high LI (24.6 +/- 5.3%, 32.3 +/- 3.8%, and 17.0 +/- 4.6%, respectively), and no organized pattern of proliferation was observed. In contrast, the mean LI of the four chordomas varied from 1.5% to 5.8%, and there was an even larger variation in the LI of different areas in individual tumors (from less than 1% to 7.5%). This finding suggests that even "slow-growing" chordomas sometimes can be locally aggressive and show a high incidence of recurrence, regardless of morphologic similarities.

    View details for Web of Science ID A1988P444300016

    View details for PubMedID 2840188

  • TREATMENT RESULTS OF JUVENILE PILOCYTIC ASTROCYTOMA JOURNAL OF NEUROSURGERY Wallner, K. E., Gonzales, M. F., Edwards, M. S., Wara, W. M., SHELINE, G. E. 1988; 69 (2): 171-176

    Abstract

    Treatment results for 36 patients with juvenile pilocytic astrocytoma treated from 1942 through 1985 at the University of California, San Francisco, were reviewed. Twenty-two tumors were located in the posterior fossa, 10 were in the hypothalamic region, and four were in the cerebral hemispheres. Twenty-eight patients were less than 18 years of age. The overall survival rate was 83% and 70% at 10 and 20 years, respectively. All 12 patients who had total tumor resection remain disease-free; only two of the 12 received postoperative irradiation. The 10- and 20-year freedom-from-progression for the 19 patients who had incomplete resection and received at least 40 Gy of postoperative irradiation was 74% and 41%, respectively. All patients who failed treatment had local recurrence. One patient developed diffuse meningeal seeding, after four local recurrences in the posterior fossa over a 23-year period. Six patients failed treatment and had a repeat biopsy at the time of recurrence or at postmortem examination, and three showed histological progression of the tumor to an anaplastic astrocytoma. Based on this study and others in the literature, a protocol has been adopted whereby patients who have total tumor resection are not treated with postoperative irradiation. Patients who have incomplete tumor resection and are older than 3 years of age are currently treated with postoperative partial-brain irradiation, to a dose of 45 to 60 Gy. In general, young children with incomplete resection are followed closely with computerized tomography or magnetic resonance imaging and are treated with chemotherapy or irradiation if tumor progression is documented.

    View details for Web of Science ID A1988P400500002

    View details for PubMedID 3392563

  • RADIOTHERAPY OF PRIMARY INTRACRANIAL GERMINOMAS - THE CASE AGAINST ROUTINE CRANIOSPINAL IRRADIATION INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Linstadt, D., Wara, W. M., Edwards, M. S., Hudgins, R. J., SHELINE, G. E. 1988; 15 (2): 291-297

    Abstract

    A retrospective study was performed on all patients with biopsy-proven intracranial germinomas and unbiopsied suprasellar or pineal region tumors treated during the past 30 years in the Department of Radiation Oncology, University of California, San Francisco. A total of 33 patients were treated: 13 with biopsy-proven germinomas, and 20 others who were unbiopsied. All patients were treated with megavoltage equipment; total dose varied between 40-55 Gy. Only two patients were treated with prophylactic spinal irradiation. No patient received initial or adjuvant chemotherapy. Follow-up times for biopsy-proven patients ranged from 0.5 to 16.7 years with a median 5.3 years. No biopsy-proven patient had a recurrence of the tumor or died; thus, actuarial relapse-free and determinate survivals at 5 years were 100%. Although only one patient in this group received prophylactic spinal irradiation, no patient failed in the spinal axis. The 20 unbiopsied patients had follow-up times ranging from 0.1 to 27.5 years with a median of 5.5 years. Six unbiopsied patients died: two from recurrent disease at the primary site, one from distant peritoneal metastases, two from complications of treatment, and one from intercurrent disease. For this group, actuarial relapse-free survival at 5 years was 72%; the corresponding determinate survival was 73%. Nineteen unbiopsied patients were treated without craniospinal irradiation. Only one developed spinal metastases. The results from this and other series indicate that the risk of spinal metastases from intracranial germinoma is too low to warrant routine prophylactic spinal irradiation. However, patients with gross tumor spill causing contamination of the CSF, malignant CSF cytology, or documented subependymal or subarachnoid metastases presumably are at higher risk for leptomeningeal failure. Craniospinal irradiation is recommended for these patients.

    View details for Web of Science ID A1988P791200006

    View details for PubMedID 3403312

  • THE PROLIFERATIVE POTENTIAL OF HUMAN EPENDYMOMAS MEASURED BY INSITU BROMODEOXYURIDINE LABELING CANCER Nagashima, T., Hoshino, T., Cho, K. G., Edwards, M. S., Hudgins, R. J., Davis, R. L. 1988; 61 (12): 2433-2438

    Abstract

    Twelve patients with ependymomas received a 30- to 60-minute intravenous infusion of bromodeoxyuridine (BrdU), 150 to 200 mg/m2 at surgery, to label tumor cells in the DNA synthesis phase. Labeled cells were detected in excised tumor specimens by indirect immunoperoxidase staining using anti-BrdU monoclonal antibody as the first antibody. The BrdU labeling index (LI, defined as the percentage of labeled cells in relation to the total number of cells scored) was calculated for each specimen. All four spinal cord ependymomas had a BrdU LI of less than 1%, which is consistent with our clinical experience that most such tumors grow slowly and have an excellent prognosis. Five of the eight intracranial ependymomas also had a low BrdU LI of approximately 1% or less, and three had a BrdU LI of 3.2%, 3.4%, and 4.8%. The latter three tumors, only one of which was diagnosed as a malignant ependymoma at the time of study, were either recurrent or recurred within 2 years after gross or subtotal removal. Cytologic analysis of cerebrospinal fluid (CSF) was performed in five cases; CSF seeding of tumor cells was found in only one patient, who had a malignant ependymoma. A high BrdU LI did not always correlate with CSF seeding. Measurement of the LI using BrdU and anti-BrdU monoclonal antibodies can provide more accurate information on the proliferative potential of individual tumors and may lead to a more rational grading system of ependymomas. The results of such studies do not always predict the potential for CSF seeding.

    View details for Web of Science ID A1988N713000006

    View details for PubMedID 3284636

  • PINEAL REGION TUMORS IN CHILDREN JOURNAL OF NEUROSURGERY Edwards, M. S., Hudgins, R. J., Wilson, C. B., Levin, V. A., Wara, W. M. 1988; 68 (5): 689-697

    Abstract

    The authors believe that the preferred treatment for pineal region tumors in children requires definitive surgery with a histological diagnosis and that a conservative approach consisting of shunting and radiation therapy no longer seems to be appropriate. The results are reported of a retrospective review of the presentation, treatment, and outcome of 36 children under the age of 18 years treated between 1974 and 1986. Eleven children had germinomas (two-cell type), seven had astrocytomas, and the remaining 18 had 15 histologically different tumor types. Surgery was performed on 30 patients; there were no deaths, but a 10% rate of persistent morbidity was found. The median follow-up period was 4 years. Nine (82%) of 11 patients with germinomas are alive without evidence of recurrence; one child died from recurrent tumor in the pineal region and another is presently being treated for recurrent tumor of the spinal cord. Six (86%) of the seven patients with astrocytoma are well after biopsy and radiation therapy. Of the remaining 18 children, five (28%) died from tumor progression. The cerebrospinal fluid (CSF) tumor markers alpha-fetoprotein and beta-human chorionic gonadotropin were helpful in determining the presence of malignant germ-cell tumors, particularly those with a poor prognosis. Magnetic resonance imaging was useful for diagnosis and for planning the operative approach. Magnetic resonance images showed the presence of pineal region tumors in four children with hydrocephalus who had no evidence of tumor on computerized tomography scans. Because the great variety of tumor types found in the pineal region must be treated in different ways and because improved microsurgical and stereotaxic surgical techniques have made mortality and morbidity rates acceptably low, a biopsy diagnosis should be obtained in all patients. Preoperative assessment of CSF tumor markers and cytology is useful for the identification of patients who have a poor prognosis.

    View details for Web of Science ID A1988N072500005

    View details for PubMedID 2451717

  • TREATMENT OF RECURRENT BRAIN-STEM GLIOMAS AND OTHER CENTRAL NERVOUS-SYSTEM TUMORS WITH 5-FLUOROURACIL, CCNU, HYDROXYUREA, AND 6-MERCAPTOPURINE NEUROSURGERY Rodriguez, L. A., Prados, M., Fulton, D., Edwards, M. S., Silver, P., Levin, V. 1988; 22 (4): 691-693

    Abstract

    Twenty-one patients with recurrent malignant central nervous system gliomas were treated with a combination of 5-fluorouracil, CCNU, hydroxyurea, and 6-mercaptopurine. Thirteen patients had brain stem gliomas, 3 patients had spinal cord gliomas, 3 patients had thalamic gliomas, and 2 patients had cerebellar astrocytomas. All patients had received radiation therapy, and 4 brain stem patients had also been treated with chemotherapy. Sixteen patients (76%) responded to treatment with either stabilization of disease or improvement. Nine of the 13 patients with brain stem gliomas (71%) had response or stabilization of disease. The median time to tumor progression (TTP) for the brain stem patients who responded or had stabilization of disease was 25 weeks. The median survival from recurrence for the brain stem glioma patients was 27 weeks. Patients with cerebellar, thalamic, and spinal cord tumors did very well, with an 87% response or stabilization of disease and a median TTP of 122 weeks.

    View details for Web of Science ID A1988M973100012

    View details for PubMedID 3374780

  • TREATMENT OF MEDULLOBLASTOMA WITH PROCARBAZINE, HYDROXYUREA, AND REDUCED RADIATION-DOSES TO WHOLE BRAIN AND SPINE JOURNAL OF NEUROSURGERY Levin, V. A., Rodriguez, L. A., Edwards, M. S., Wara, W., Liu, H. C., Fulton, D., Davis, R. L., Wilson, C. B., Silver, P. 1988; 68 (3): 383-387

    Abstract

    Forty-seven patients with medulloblastoma were treated postoperatively with procarbazine, followed by craniospinal radiation therapy in combination with hydroxyurea. The radiation dose to the posterior fossa was 55 Gy; the spinal cord received 25 Gy and the whole brain 25 to 35 Gy (mean 33 Gy). Seventeen tumors recurred. Only one initial recurrence was in the spinal subarachnoid space; 10 (59%) were in the posterior fossa, and four (24%) were supratentorial. The estimated 5-year disease-free survival probability was 55%; the 5-year overall survival rate was 66%. Myelotoxicity occurred in 38% of patients, but in only one case was it severe enough to warrant reducing the total dose of radiation. It was concluded that good-risk medulloblastoma patients may be treated with radiation dosages as low as 25 Gy to the spinal axis and to the whole brain without increasing the risk of recurrence outside the posterior fossa. Chemotherapy with procarbazine followed by radiation therapy and hydroxyurea during radiation therapy was well tolerated and may play a role in reducing radiation dosages outside the posterior fossa.

    View details for Web of Science ID A1988M305500006

    View details for PubMedID 3343610

  • REVERSIBLE TRUE PRECOCIOUS PUBERTY SECONDARY TO A CONGENITAL ARACHNOID CYST AMERICAN JOURNAL OF DISEASES OF CHILDREN Clark, S. J., VANDOP, C., Conte, F. A., Grumbach, M. M., Berger, M. S., Edwards, M. S. 1988; 142 (3): 255-256

    View details for Web of Science ID A1988M309000011

    View details for PubMedID 3344710

  • PARTIAL CHARACTERIZATION OF A SOLUBLE MITOGENIC FACTOR FROM MEDULLOBLASTOMA JOURNAL OF NEUROSURGERY Rutka, J. T., Hall, J., GIBLIN, J. R., DOUGHERTY, D. V., Edwards, M. S., Stern, R., Rosenblum, M. L. 1988; 68 (2): 251-258

    Abstract

    To determine how medulloblastoma cells might influence the proliferation and phenotype of normal stromal cells, normal human leptomeningeal cells were treated in culture with medulloblastoma-conditioned medium; their ability to incorporate tritiated thymidine and synthesize collagen was measured. The treated leptomeningeal cells had a significantly greater uptake of tritiated thymidine and grew faster than control leptomeningeal cells. Immunofluorescence studies demonstrated a greater intensity of staining for procollagen type III in the cell layer of the treated cultures than in control cultures; diethylaminoethyl (DEAE)-cellulose chromatography of the medium showed that the treated cells synthesized predominantly type III collagen, whereas control cells synthesized type I collagen. Analysis of the medulloblastoma-conditioned medium revealed that the soluble factor responsible for these effects in an acid- and heat-stable protein. The increased proliferation and altered collagen synthesis induced in leptomeningeal cell cultures by a soluble factor from a medulloblastoma are examples of how tumor and stromal elements interact, and may be related to the process of desmoplasia often observed in medulloblastomas in vivo.

    View details for Web of Science ID A1988L906400013

    View details for PubMedID 3339442

  • PRESSURE, BIOCHEMICAL, AND CULTURE CHARACTERISTICS OF CSF ASSOCIATED WITH THE INUTERO DRAINAGE OF VARIOUS FETAL CNS DEFECTS AMERICAN JOURNAL OF MEDICAL GENETICS SIMPSON, G. F., Edwards, M. S., Callen, P., FILLY, R. F., Anderson, R. L., Golbus, M. S. 1988; 29 (2): 343-351

    Abstract

    An attempt has been made to begin delineation of the in utero dynamics of fetal intracranial fluid in the presence of brain malformations. In a series of patients with fetal CNS defects, cephalocentesis was performed at the time of therapeutic abortion or to facilitate vaginal delivery. Intracranial CSF pressures and volumes were quite variable. There did not appear to be any discernible correlation between the type of lesion and the intracranial pressure. Fetal CSF glucose levels were moderately depressed and protein concentrations were very high. Neither virus nor bacteria were cultured from fetal CSF or amniotic fluid of any patients in this series.

    View details for Web of Science ID A1988M257600012

    View details for PubMedID 3354605

  • Recurrent malignant gliomas: survival following interstitial brachytherapy with high-activity iodine-125 sources. Journal of neurosurgery Gutin, P. H., Leibel, S. A., Wara, W. M., Choucair, A., Levin, V. A., PHILIPS, T. L., Silver, P., Da Silva, V., Edwards, M. S., Davis, R. L. 1987; 67 (6): 864-873

    Abstract

    The authors report survival data for the first 41 patients treated for recurrent malignant gliomas with interstitial brachytherapy at the University of California, San Francisco (1980-1984). Iodine-125 (125I) sources were temporarily implanted using stereotaxic techniques. The median survival period for 18 patients with recurrent glioblastomas was 52 weeks after brachytherapy; two patients are alive more than 5 years after brachytherapy. The median survival period for 23 patients with recurrent anaplastic astrocytomas is 153 weeks after brachytherapy, with 10 patients alive more than 3 years and four patients alive more than 4 years after brachytherapy. Both groups did significantly better (p less than 0.01) than groups of patients with the same diagnoses and similar general characteristics who were treated at recurrence with chemotherapy alone. Because of deterioration of their clinical condition and evidence of recurrence from computerized tomographic scans, 17 (41%) of 41 patients required reoperation 20 to 72 weeks after brachytherapy. Despite the invariable presence of apparently viable tumor cells mixed with necrotic tissue in the resected specimen, nine patients have survived more than 2 years after reoperation and two of the nine are still alive 4 years after reoperation. The authors conclude that brachytherapy with temporarily implanted 125I sources for well-circumscribed, hemispheric, recurrent malignant gliomas is effective and offers a chance for long-term survival even though focal radiation necrosis can seriously degrade the quality of survival in a minority of patients.

    View details for PubMedID 3316532

  • GROWTH OF A MEDULLOBLASTOMA ON NORMAL LEPTOMENINGEAL CELLS IN CULTURE - INTERACTION OF TUMOR-CELLS AND NORMAL-CELLS NEUROSURGERY Rutka, J. T., DOUGHERTY, D. V., GIBLIN, J. R., Edwards, M. S., McCulloch, J. R., Rosenblum, M. L. 1987; 21 (6): 872-878

    Abstract

    Well-characterized medulloblastoma cells growing in suspension were placed on top of a confluent monolayer of leptomeningeal cells. In contrast to cells placed on plastic alone, which did not grow or attach, the medulloblastoma cells attached readily to the leptomeningeal cells and grew to form enlarging spheroids. The growth of these spheroids was supported with minimal essential medium containing 10% fetal calf serum or with human cerebrospinal fluid. Medulloblastoma cells grown on plastic remained viable for 7 to 10 days, whereas those grown on a monolayer of leptomeningeal cells remained viable for 40 days. Electron microscopy demonstrated increased interdigitation of the plasma membrane at the sites of contact between leptomeningeal and medulloblastoma cells, the deposition of fine, basement membrane-like material between the two cell types, and an increased number of cytoskeletal filaments in the leptomeningeal cells. We conclude that medulloblastoma cells can be grown on a leptomeningeal monolayer. This in vitro system may be useful in studying the mechanisms by which medulloblastoma cells attach to leptomeningeal elements and grow after dissemination in cerebrospinal fluid.

    View details for Web of Science ID A1987L495700015

    View details for PubMedID 3437956

  • MAGNETIC-RESONANCE-IMAGING OF SYRINGOMYELIA ASSOCIATED WITH AN EXTRAMEDULLARY SPINAL-CORD TUMOR - CASE-REPORT NEUROSURGERY RHYNER, P. A., Hudgins, R. J., Edwards, M. S., BRANTZAWADZKI, M. 1987; 21 (2): 233-235

    Abstract

    The association of syringomyelia and extramedullary spinal cord tumors is rare. We present the case of a patient with this association documented by magnetic resonance imaging and discuss the unusual features of the syrinx.

    View details for Web of Science ID A1987J587300019

    View details for PubMedID 3658135

  • CRANIOSYNOSTOSIS AND HYDROCEPHALUS NEUROSURGERY Golabi, M., Edwards, M. S., Ousterhout, D. K. 1987; 21 (1): 63-67

    Abstract

    Ten cases of craniosynostosis associated with hydrocephalus were found in a retrospective review of 250 cases of children with craniosynostosis. Four children had Pfeiffer's syndrome, 3 had Crouzon's syndrome, 2 had kleeblattschädel with multiple anomalies and therefore could not be classified into a definite syndrome, and 1 had isolated sagittal synostosis. Of these 10 children, 5 had kleeblattschädel, two with Crouzon's syndrome, one with Pfeiffer's syndrome, and 2 with multiple anomalies. In all patients, hydrocephalus was controlled by a shunting procedure. Possible causes of hydrocephalus in association with craniosynostosis are discussed.

    View details for Web of Science ID A1987J131300012

    View details for PubMedID 3614607

  • MAGNETIC-RESONANCE-IMAGING AND MANAGEMENT OF A PINEAL REGION DERMOID SURGICAL NEUROLOGY Hudgins, R. J., RHYNER, P. A., Edwards, M. S. 1987; 27 (6): 558-562

    Abstract

    We report the case of a 19-year-old man harboring a pineal region dermoid, of which only eight other cases have been reported. A diagnosis was made with magnetic resonance imaging (MRI), which showed a marked high signal intensity on both T-1 and T-2 weighted images that is consistent with the lipid character of the lesion. Residual tumor could be seen on postoperative MR images. MRI is an accurate, noninvasive modality for the diagnosis and follow-up evaluation of these tumors.

    View details for Web of Science ID A1987H312900009

    View details for PubMedID 3576432

  • BRACHYTHERAPY OF RECURRENT TUMORS OF THE SKULL BASE AND SPINE WITH I-125 SOURCES NEUROSURGERY Gutin, P. H., Leibel, S. A., Hosobuchi, Y., Crumley, R. L., Edwards, M. S., Wilson, C. B., Lamb, S., Weaver, K. A. 1987; 20 (6): 938-945

    Abstract

    Thirteen patients with recurrent, previously irradiated tumors of the skull base or spine were reirradiated with 125I sources implanted interstitially using microsurgical or stereotactic techniques. Patients harbored difficult, end-stage recurrences of chordoma, meningioma, malignant meningioma, fibrosarcoma, invasive pituitary adenoma, and malignant schwannoma. In two other patients with malignant meningioma, the dose of external radiation was augmented by implanting 125I sources during the initial operation for excision of the lesion or at a separate surgical procedure after conventional teletherapy. Microsurgical implantation of 125I sources into basal tumors was limited by the difficulties inherent in operating in this region; it is not possible to visualize the entire tumor that requires implantation. Three of five chordomas stabilized or regressed; these patients probably benefited from the procedure. Two patients with recurrent malignant meningiomas had long term remission after interstitial brachytherapy. Interstitial 125I brachytherapy for recurrent tumors at the base of skull or adjacent to the spine can be more successful only if more aggressive surgical exposures of these regions are attempted. Implantation of sources for a "boost" dose, either microsurgically during the initial surgical resection of the lesion before conventional teletherapy or stereotactically after conventional teletherapy, may be a valuable adjunct to external irradiation for the control of potentially devastating tumors (such as chordomas and malignant meningiomas) before they recur with the severe consequences seen in the patients reported here.

    View details for Web of Science ID A1987H883500019

    View details for PubMedID 3614575

  • OUTCOME OF BRAIN-ABSCESS TREATMENT IN CHILDREN - REDUCED MORBIDITY WITH NEUROIMAGING PEDIATRIC NEUROLOGY Ferriero, D. M., DERECHIN, M., Edwards, M. S., Berg, B. O. 1987; 3 (3): 148-152

    Abstract

    Records were reviewed of 17 patients, ages 4 months to 18 years, who had been diagnosed as having brain abscesses between 1975-1984. Serial computed tomography was used to guide treatment; consequently, 8 patients were managed medically and 9 received surgical intervention. All medically treated patients were free of neurologic residua upon subsequent examination. Positive identification of organisms from systemic cultures and close computed tomographic monitoring prevented the need for surgical intervention in these patients. The surgically treated patients were sicker at presentation, and of the 9 patients requiring surgical intervention, 4 had neurologic sequelae and 1 patient died. Brain abscess aspiration or excision revealed organisms in 7 of the 9 surgically treated patients. The reduction in morbidity and mortality was due in part to early recognition and monitoring of abscess size with contrast-enhanced computed tomography and avoidance of surgical excision of the abscess.

    View details for Web of Science ID A1987H850200004

    View details for PubMedID 3508060

  • CRANIOMETAPHYSEAL DYSPLASIA ASSOCIATED WITH HYDROCEPHALUS - CASE-REPORT NEUROSURGERY Hudgins, R. J., Edwards, M. S. 1987; 20 (4): 617-618

    Abstract

    Craniometaphyseal dysplasia is a rare bone disorder that may cause a variety of neurological abnormalities; hydrocephalus has not been observed with this disorder, however. A case of craniometaphyseal dysplasia associated with hydrocephalus is reported, and possible causes are discussed.

    View details for Web of Science ID A1987G900500019

    View details for PubMedID 3587556

  • CEREBRAL PTOSIS WITH CONTRALATERAL ARTERIOVENOUS MALFORMATION - A REPORT OF 2 CASES ANNALS OF NEUROLOGY Lowenstein, D. H., Koch, T. K., Edwards, M. S. 1987; 21 (4): 404-407

    Abstract

    We describe two patients with chronic unilateral ptosis and contralateral hemispheric arteriovenous malformations. Both patients were brought to our attention after a subacute or acute neurological deterioration. Analysis of prior photographs showed the ptosis progressed up to the time of presentation and significantly resolved following surgical removal of the arteriovenous malformation. The partially reversible and chronic nature of the ptosis in these two patients represents a particularly unusual forms of cerebral ptosis.

    View details for Web of Science ID A1987G819700014

    View details for PubMedID 3579226

  • MR IMAGING OF INTRACRANIAL TUBEROUS SCLEROSIS AMERICAN JOURNAL OF ROENTGENOLOGY MCMURDO, S. K., Moore, S. G., BRANTZAWADZKI, M., Berg, B. O., Koch, T., Newton, T. H., Edwards, M. S. 1987; 148 (4): 791-796

    Abstract

    The role of MR in evaluating tuberous sclerosis is reviewed in 15 patients. These studies were compared with CT scans, which were available in 14 patients. Four characteristic findings were noted on the MR images obtained. Subependymal nodules projecting into the lateral ventricles were seen in 12 of 15 patients on T1-weighted images. This was the most specific finding. Distortion of the normal cortical architecture was seen in 10 of 11 patients in whom T1-weighted images were obtained using a 256 X 256 matrix. These foci corresponded to multiple cortical areas of increased signal on T2-weighted images. Dilated ventricles were seen in five patients. In one patient, a known astrocytoma showed increased signal on the T2-weighted images, allowing differentiation from a benign subependymal nodule. MR depicted the cortical hamartomas more completely than did CT. The MR scans were abnormal in all cases, and a diagnosis could be confidently made in all 11 cases scanned using a 256 X 256 matrix. Our preliminary experience suggests that MR will at least equal and probably exceed CT, both for sensitivity and specificity, given the use of a 256 X 256 matrix.

    View details for Web of Science ID A1987G479900031

    View details for PubMedID 3493666

  • AUTOGENEIC SKULL BONE-GRAFTS TO RECONSTRUCT LARGE OR COMPLEX SKULL DEFECTS IN CHILDREN AND ADOLESCENTS NEUROSURGERY Edwards, M. S., Ousterhout, D. K. 1987; 20 (2): 273-280

    Abstract

    Autogeneic split or free skull bone grafts harvested at the time of operation were used to repair large or complex skull defects in 19 children; in 2 children, autogeneic fresh rib grafts were also used. Follow-up examinations for periods of 1 and 7 years showed that the use of autogeneic grafts is superior to the use of materials such as acrylic or metals for cranioplasty in children.

    View details for Web of Science ID A1987G032900013

    View details for PubMedID 3561736

  • CURRENT MANAGEMENT OF BRAIN-STEM GLIOMAS PEDIATRIC NEUROSCIENCE Edwards, M. S., Prados, M. 1987; 13 (6): 309-315

    Abstract

    Brain stem gliomas constitute 10-20% of central nervous system tumors in children. Management of these tumors remains controversial. In general, the prognosis for long-term survival is poor, but brain stem gliomas represent a heterogeneous population of tumors, some of which have a better prognosis than others. Improvements in diagnostic imaging techniques, particularly the availability of magnetic resonance imaging, provide the means to differentiate among these populations. Advances in radiation therapy may provide the means to improve survival. In this article we review the reported series and the present state of the art for the diagnosis and management of children with brain stem gliomas.

    View details for Web of Science ID A1987Q088800004

    View details for PubMedID 3332719

  • MANAGEMENT OF INFRATENTORIAL BRAIN-TUMORS PEDIATRIC NEUROSCIENCE Hudgins, R. J., Edwards, M. S. 1987; 13 (4): 214-222

    Abstract

    Because 60-70% of brain tumors in children occur in the posterior fossa, the pediatric neurosurgeon must be familiar with the specialized techniques necessary for successful surgery in this region. We discuss the preoperative evaluation, surgical techniques, and postoperative management for children harboring infratentorial brain tumors. Using this approach to treatment, we have had no operative mortalities, a 2% rate of infection, a 15% rate of transient neurologic deficit, and a 5% rate of permanent neurologic deficit.

    View details for Web of Science ID A1987N870700008

    View details for PubMedID 3454444

  • UNUSUAL POSTERIOR-FOSSA DURAL ARTERIOVENOUS MALFORMATION IN A NEONATE - CASE-REPORT NEUROSURGERY Ross, D. A., Walker, J., Edwards, M. S. 1986; 19 (6): 1021-1024

    Abstract

    We report the case of an infant born with an unusual posterior fossa dural arteriovenous malformation that was supplied by the entire intracranial circulation. The lesion caused hydrocephalus and congestive heart failure that led to the infant's death.

    View details for Web of Science ID A1986F261900020

    View details for PubMedID 3808233

  • PEDIATRIC CENTRAL-NERVOUS-SYSTEM TUMORS - A CELL KINETIC-STUDY WITH BROMODEOXYURIDINE NEUROSURGERY Murovic, J. A., Nagashima, T., Hoshino, T., Edwards, M. S., Davis, R. L. 1986; 19 (6): 900-904

    Abstract

    Bromodeoxyuridine (BrdU), 150 to 200 mg/m2, was administered at the time of operation to 20 pediatric patients with neuroectodermal tumors to label tumor cells in the S phase. Immunocytochemical techniques were used on excised tumor specimens to detect cells containing BrdU, and the BrdU labeling index (LI) was calculated as the number of BrdU-labeled cells divided by the total number of cells counted. Four medulloblastomas, three glioblastomas multiforme, and two highly anaplastic astrocytomas had average BrdU LIs of 13.0 +/- 3.0% (SE), 12.7 +/- 4.3%, and 14.6 +/- 6.7%, respectively. Three of nine moderately anaplastic astrocytomas had BrdU LIs of greater than 1% (average, 6.5 +/- 2.4%), whereas six had LIs of less than 1%. In two juvenile pilocytic astrocytomas, which are considered slow-growing, the BrdU LIs were unexpectedly high, averaging 6.5 +/- 1.4%. Thus pediatric medulloblastomas, glioblastomas multiforme, highly anaplastic astrocytomas, and a minority of moderately anaplastic astrocytomas had high proliferative potentials, whereas most of the moderately anaplastic astrocytomas had low proliferative potentials. Although the number of cases in this study is still too small to yield statistically significant comparisons, the results indicate that some pediatric tumors have considerably higher LIs than histologically similar adult tumors studied previously.

    View details for Web of Science ID A1986F261900003

    View details for PubMedID 3027608

  • DEVELOPMENT OF MULTIPLE LESIONS DURING RADIATION-THERAPY AND CHEMOTHERAPY IN PATIENTS WITH GLIOMAS JOURNAL OF NEUROSURGERY Choucair, A. K., Levin, V. A., Gutin, P. H., Davis, R. L., Silver, P., Edwards, M. S., Wilson, C. B. 1986; 65 (5): 654-658

    Abstract

    To determine the percentage of patients who developed multiple central nervous system (CNS) gliomas during postoperative radiation therapy and chemotherapy, the authors reviewed the records of 1047 patients treated between December 2, 1976, and August 16, 1985, who had an original diagnosis of supratentorial glioblastoma multiforme or other anaplastic glioma. The occurrence of multiple lesions was verified by neurodiagnostic studies (computerized tomography or myelography) or by findings at operation or autopsy. Twelve patients (1.1%) who presented with multiple lesions were excluded from this analysis. There were 405 patients with glioblastoma multiforme; their median age was 46.5 years (range 22 to 70 years). Eighteen (5%) of these patients had multiple CNS lesions, five of which were in the spinal cord. The median time from diagnosis to detection of the second lesion in this group was 59.5 weeks (range 10 to 182 weeks). There were 630 patients with anaplastic glioma (which included mixed malignant glioma and highly anaplastic, gemistocytic, moderately anaplastic, and anaplastic astrocytomas); their median age was 30 years (range 2 to 62 years). Fifty-four (8.6%) of these patients had multiple lesions, 10 of which were in the spinal cord; only one case of extraneural metastasis was found. The median time from diagnosis to detection of the second lesion in this group was 101 weeks (range 14 to 459 weeks). These results show that more than 90% of CNS gliomas recur at the site of the original tumor. Considering the high frequency of intellectual dysfunction after whole-brain radiation therapy, the use of focal radiation fields appears to be the most judicious approach to the treatment of patients with gliomas.

    View details for Web of Science ID A1986E529600012

    View details for PubMedID 3021931

  • RETREATMENT OF PEDIATRIC BRAIN-TUMORS WITH RADIATION AND MISONIDAZOLE - RESULTS OF A CCSG RTOG PHASE-I/II STUDY CANCER Wara, W. M., Wallner, K. E., Levin, V. A., Liu, H. C., Edwards, M. S. 1986; 58 (8): 1636-1640

    Abstract

    Twenty-nine patients with recurrent pediatric brain tumors after full-dose treatment with radiation were retreated with misonidazole (9 gm/m2) and whole-brain irradiation (300 rad X 10). Seventeen of 29 patients (59%) experienced nausea and vomiting with misonidazole administration and 6 patients (21%) developed peripheral neuropathy. Serum levels of misonidazole were similar to those reported for adults. One patient died of trauma shortly after retreatment. For the remaining 28 patients, the median time-to-progression was 5.5 months. Median survival was 13 months. Six patients (21%) developed radiation toxicity, two of whom died from the toxicity. Whereas the results on this study are similar to reported series of patients receiving salvage chemotherapy for recurrent pediatric brain tumors, more effective treatment clearly is needed.

    View details for Web of Science ID A1986E241100009

    View details for PubMedID 3756787

  • S-PHASE FRACTION OF HUMAN-BRAIN TUMORS INSITU MEASURED BY UPTAKE OF BROMODEOXYURIDINE INTERNATIONAL JOURNAL OF CANCER Hoshino, T., Nagashima, T., Cho, K. G., Murovic, J. A., Hodes, J. E., Wilson, C. B., Edwards, M. S., Pitts, L. H. 1986; 38 (3): 369-374

    Abstract

    One hundred fifty-four patients with brain tumors of various types were given an intravenous infusion of the thymidine analogue bromodeoxyuridine (BUdR), 200 mg/m2, at the time of surgery but before biopsy of the tumor to label S-phase cells. Excised tumor specimens were fixed, sectioned, and stained by immunoperoxidase methods to detect BUdR. The labelling index (LI), or percentage of BUdR-labelled cells, was calculated for each tumor specimen. The LIs of glioblastomas, medulloblastomas, and most highly anaplastic astrocytomas were 5% to 20%. The majority of moderately anaplastic astrocytomas showed LIs of less than 1%, but 30% of them had LIs similar to those of highly malignant gliomas. Most pituitary adenomas and neurinomas showed LIs of less than 1%. Nonmalignant meningiomas had LIs of less than 1%, whereas malignant meningiomas had LIs higher than 2.7%. This is an important observation, because malignant meningiomas are not well-defined histopathologically and their growth rate and rate of recurrence cannot be predicted by current diagnostic procedures. By estimating the proliferative potential of individual tumors more precisely, the BUdR LI supplements histopathological diagnosis, allowing a more accurate estimate of prognosis and facilitating the design of treatment regimens for individual patients.

    View details for Web of Science ID A1986E037800010

    View details for PubMedID 3527993

  • INTRAMEDULLARY NEURILEMOMAS OF THE SPINAL-CORD - REPORT OF 2-CASES AND REVIEW OF THE LITERATURE NEUROSURGERY Ross, D. A., Edwards, M. S., Wilson, C. B. 1986; 19 (3): 458-464

    Abstract

    Two patients harboring intramedullary neurilemomas of the spinal cord are presented. Published reports of these rare lesions and possible mechanisms of their origin are reviewed. Based on the authors' experience and review of the literature, they think that the treatment of choice for these rare lesions is laminectomy and resection and that intraoperative frozen section diagnosis is essential. Incorrect interpretation of the biopsy material that suggests an original diagnosis of infiltrating glioma, perhaps because a neurilemoma was not expected, has made second operations necessary.

    View details for Web of Science ID A1986D956000024

    View details for PubMedID 3531912

  • SPINAL INTRAMEDULLARY SPREAD OF MEDULLOBLASTOMA - CASE-REPORT JOURNAL OF NEUROSURGERY Barnwell, S. L., Edwards, M. S. 1986; 65 (2): 253-255

    Abstract

    The case of an 11-year-old boy is reported in whom two intramedullary lesions developed at the thoracic-cervical and thoracic-lumbar junctions 2 1/2 years after resection and irradiation of a medulloblastoma in the posterior fossa. There was no evidence of subarachnoid spread of the tumor. Magnetic resonance imaging was used to localize these lesions, and provided much better diagnostic information than either computerized tomography scans or myelograms.

    View details for Web of Science ID A1986D331900020

    View details for PubMedID 3723185

  • INTRACRANIAL ARACHNOID CYSTS IN CHILDREN JOURNAL OF NEUROSURGERY Harsh, G. R., Edwards, M. S., Wilson, C. B. 1986; 64 (6): 835-842

    Abstract

    The clinical and radiographic findings, surgical treatment, and outcome in 16 pediatric patients with intracranial arachnoid cysts are reviewed. The clinical presentation reflected the anatomical location of the lesions. Computerized tomography or magnetic resonance imaging scans were diagnostic in all cases. Of the nine cysts treated primarily or secondarily by craniotomy for fenestration and drainage into the basilar cisterns, five recurred. Cyst-peritoneal shunting led to diminished cyst size and clinical improvement in all seven cases in which it was used as the initial treatment and in all four cases in which fenestration had been unsuccessful. The results in this series show that cyst-peritoneal shunting is the treatment of choice for most intracranial arachnoid cysts in children.

    View details for Web of Science ID A1986C648700001

    View details for PubMedID 3701434

  • INSITU CELL-KINETICS STUDIES ON HUMAN NEUROECTODERMAL TUMORS WITH BROMODEOXYURIDINE LABELING JOURNAL OF NEUROSURGERY Hoshino, T., Nagashima, T., Murovic, J. A., Wilson, C. B., Edwards, M. S., Gutin, P. H., Davis, R. L., DeArmond, S. J. 1986; 64 (3): 453-459

    Abstract

    Thirty-eight patients undergoing surgical removal of neuroectodermal tumors of the central nervous system were given a 1-hour intravenous infusion of bromodeoxyuridine (BUdR), 150 to 200 mg/sq m, to label tumor cells in the deoxyribonucleic acid (DNA) synthesis phase (S-phase). The excised tumor specimens were divided into two portions: one was fixed with 70% ethanol and embedded in paraffin and the other was digested with an enzyme cocktail to make a single-cell suspension. The paraffin-embedded tissues were stained by an indirect peroxidase method using anti-BUdR monoclonal antibody (MA) as the first antibody. Single-cell suspensions were reacted with fluorescein isothiocyanate (FITC)-conjugated anti-BUdR MA's for flow cytometric analysis. S-phase cells that had incorporated BUdR into their DNA were well stained by both methods. The percentage of BUdR-labeled cells, or S-phase fraction, was calculated in tissue sections by microscopic examination and in single-cell suspensions by flow cytometric analysis. The biological malignancy of the tumors was reflected in the S-phase fractions, which were 5% to 20% for glioblastoma multiforme, medulloblastoma, and highly anaplastic astrocytoma, but less than 1% in most moderately anaplastic astrocytomas, ependymomas, and mixed gliomas. Two juvenile pilocytic astrocytomas and two low-grade astrocytomas from children had high S-phase fraction despite the fairly benign and slow-growing nature of these tumors. These results indicate that the S-phase fraction obtained immunocytochemically with anti-BUdR MA's may provide useful information in estimating the biological malignancy of human central nervous system tumors in situ.

    View details for Web of Science ID A1986A236000015

    View details for PubMedID 3950723

  • UROLOGICAL ASPECTS OF THE TETHERED CORD SYNDROME JOURNAL OF UROLOGY Hellstrom, W. J., Edwards, M. S., Kogan, B. A. 1986; 135 (2): 317-320

    Abstract

    We performed urological evaluations in 18 patients with the tethered spinal cord syndrome. Of the patients 4 had low grade vesicoureteral reflux but none had significant upper tract anomalies. Urodynamic studies documented a flaccid bladder in 9 patients (5 with supersensitivity to bethanechol), an uninhibited bladder in 5, mixed bladder dysfunction in 2 and normal function in 2. Repeat urodynamic studies were performed in 15 patients at least 6 months after release of the tethering. Of 8 patients with flaccid bladders studied postoperatively 6 had significant changes: 2 became normal, 2 had limited contractions and 2 had evidence of upper motor neuron abnormalities. Supersensitivity to bethanechol was of no predictive value. All 4 patients with uninhibited bladders who were evaluated preoperatively and postoperatively had improved and 3 currently are entirely normal. Careful urological evaluation of patients with the tethered spinal cord syndrome is helpful not only for diagnosis but also for appropriate management preoperatively and postoperatively. The fact that lower urinary tract function improves in some patients should encourage early and aggressive neurosurgical management of patients with this syndrome.

    View details for Web of Science ID A1986AYT3300028

    View details for PubMedID 3944868

  • An evaluation of the in utero neurosurgical treatment of ventriculomegaly. Clinical neurosurgery Edwards, M. S. 1986; 33: 347-357

    Abstract

    Clinical results for in utero treatment of ventriculomegaly are not impressive; results may improve, however, with new techniques and more experience. Nonetheless, even in the best of hands, it is not always possible to identify associated and sometimes fatal congenital abnormalities on high resolution obstetric ultrasonograms, and not enough is known of the natural history of CNS congenital disease, in particular of ventriculomegaly, to select the appropriate fetus for in utero treatment. Results of animal studies are encouraging, but more work is needed to define the pathophysiology, knowledge of which might allow selection of the appropriate fetus and treatment modality.

    View details for PubMedID 3098489

  • Posterior fossa hemorrhage in term newborns. Pediatric neurology Koch, T. K., JAHNKE, S. E., Edwards, M. S., Davis, S. L. 1985; 1 (2): 96-99

    Abstract

    Posterior fossa hemorrhage detected by computed tomography (CT) in seven term newborns was managed by nonsurgical means. All infants were developmentally normal two to four years later with the exception of one infant who died with a massive posterior fossa hemorrhage. Two infants with extensive hemorrhages developed hydrocephalus. Spinal fluid drainage and diuretic therapy resulted in the resolution of hydrocephalus in one infant and delayed the placement of a ventriculoperitoneal shunt in the other. This series documents normal outcome in nonsurgically managed neonatal posterior fossa hemorrhages of varying degrees of severity.

    View details for PubMedID 3880397

  • HEMANGIOMATOUS ANOMALY OF BONE IN CROUZONS SYNDROME - CASE-REPORT NEUROSURGERY Alpers, C. E., Edwards, M. S. 1985; 16 (3): 391-394

    Abstract

    A striking and diffuse hemangiomatous architecture was identified by microscopic examination of bone specimens obtained at cranial synostectomy and from the craniofacial area of a young boy with Kleeblättschadel deformity and Crouzon's syndrome. A retrospective review of the histopathological appearance of bone specimens from other patients with Crouzon's syndrome treated on our service and a review of the literature on craniosynostosis suggest that the hemangiomatous pattern seen in this patient is rare if not unique. The unusual pathological findings provide evidence that the underlying pathophysiology of this disorder may be heterogeneous.

    View details for Web of Science ID A1985ADN1300019

    View details for PubMedID 3982620

  • AN UNUSUAL SPINAL MENINGIOMA IN A CHILD - CASE-REPORT NEUROSURGERY Liu, H. C., DeArmond, S. J., Edwards, M. S. 1985; 17 (2): 313-316

    Abstract

    Meningiomas seldom occur in children, and spinal meningioma in a child is rare. We report the case of a boy, 3 years and 5 months of age, who had an unusual atypical meningioma involving the subarachnoid space from T-2 to the cauda equina. To our knowledge, no similar case has been reported previously.

    View details for Web of Science ID A1985AND3100011

    View details for PubMedID 4033882

  • EFFECT OF HEMATOPORPHYRIN DERIVATIVE PHOTORADIATION THERAPY ON SURVIVAL IN THE RAT 9L GLIOSARCOMA BRAIN-TUMOR MODEL JOURNAL OF NEUROSURGERY Boggan, J. E., Bolger, C., Edwards, M. S. 1985; 63 (6): 917-921

    Abstract

    Intracerebral tumors were produced in 99 rats by stereotaxic implantation of 9L gliosarcoma brain-tumor cells. Hematoporphyrin derivative (HPD), 10 or 20 mg/kg, was administered as an intravenous bolus 24 or 48 hours before irradiation of the tumor region with light from an argon pumped-dye laser (632 nm). Laser light, at a dose of 30, 60, or 200 joules/sq cm, was delivered through a craniectomy 10 or 13 days after tumor implantation. Survival times were significantly prolonged in rats exposed to laser light at a dose of 200 joules/sq cm 24 hours after administration of HPD, 20 mg/kg.

    View details for Web of Science ID A1985AVB4300015

    View details for PubMedID 2932542

  • OUTCOME FROM SEVERE HEAD-INJURY IN CHILDREN AND ADOLESCENTS JOURNAL OF NEUROSURGERY Berger, M. S., Pitts, L. H., Lovely, M., Edwards, M. S., Bartkowski, H. M. 1985; 62 (2): 194-199

    Abstract

    A consecutive series of 37 children (17 years old and under) with severe head injury is presented. The data confirm that morbidity and mortality are lower in children than in adults: 51% of these young patients had a good recovery or moderate disability at 6 months. The mortality rate in this series (33%) is higher than in some reports, but probably more closely approximates the death rate from these injuries in an unselected pediatric population than do statistics from tertiary care hospitals. There was no significant relationship between age and outcome in this age group, but mass lesions and uncontrolled intracranial hypertension adversely affected outcome. Diffuse cerebral swelling was commonly seen on computerized tomography scans, and generally was associated with a satisfactory outcome (75%). Two of 13 deaths were considered preventable, emphasizing the narrow therapeutic safety margin and extreme care required in treating these patients.

    View details for Web of Science ID A1985AAU5900005

    View details for PubMedID 3968558

  • EVALUATION OF SR-2508 INDUCED NEUROTOXICITY AND MYOTOXICITY IN RATS USING BRAIN-STEM AUDITORY EVOKED-POTENTIALS AND THE POSTERIOR AURICULAR MUSCLE RESPONSE INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Gordon, D. G., Edwards, M. S. 1985; 11 (10): 1805-1807

    Abstract

    Brainstem auditory evoked potential (BAEPs) and a middle latency component attributed to the posterior auricular muscle response (PAMR) to an intense auditory stimulus were used to measure the onset of neurotoxic and myotoxic effects in rats after chronic exposure to the radiosensitizer SR-2508. The rats received intraperitoneal injections of SR-2508, 500 mg/kg, 5 days/week for 6 weeks. BAEP and PAMR were measured after 10, 20, and 30 injections and 4 weeks after the drug treatment was stopped. A significant neurotoxic effect was observed: After 10 injections of SR-2508, latency of the fourth positive (P4) component of the BAEP, which is thought to represent activity from the superior olivary nuclei, increased from baseline levels, and a further increase was measured after 30 injections. Four weeks after drug treatment was stopped, P4 latency had not returned to baseline levels, indicating permanent injury. PAMR latency was also increased after 10 injections of SR-2508, but increased no further during the drug treatment period. Four weeks after the last injection, PAMR latencies had returned to pretreatment levels, indicating that the myotoxic effects of SR-2508 were reversible.

    View details for Web of Science ID A1985ARU7900010

    View details for PubMedID 2931411

  • POSTIRRADIATION CEREBELLAR GLIOMA - CASE-REPORT JOURNAL OF NEUROSURGERY Raffel, C., Edwards, M. S., Davis, R. L., Ablin, A. R. 1985; 62 (2): 300-303

    Abstract

    A 13-year-old girl developed an anaplastic astrocytoma of the cerebellum 7 years after irradiation of the central nervous system and prophylactic chemotherapy for acute lymphocytic leukemia. The fact that the astrocytoma was anaplastic and infiltrative was unusual for astroglial tumors at this site. It is proposed that this is a radiation-induced glioma.

    View details for Web of Science ID A1985AAU5900023

    View details for PubMedID 3855445

  • SYSTEMIC STAGING OF SUPRATENTORIAL EXTRA-AXIAL BRAIN-TUMORS IN CHILDREN - CRANIOPHARYNGIOMAS, ATYPICAL TERATOMA AND TERATOID TUMORS OF THE SUPRASELLAR REGION (GERMINOMAS), AND INTRACRANIAL TERATOMAS CANCER James, H. E., Edwards, M. S. 1985; 56 (7): 1800-1803

    Abstract

    A staging system has been proposed for the following tumors: craniopharyngiomas, germinomas, and intracranial teratomas. Various aspects of the specific pathologic and growth characteristics of the tumor determines such categorization and subclassification of the tumors. A brief analysis of the clinical aspects in reference to classification is presented. The suggested systems will need to be tested in clinical studies to determine their validity.

    View details for Web of Science ID A1985AQR3200014

    View details for PubMedID 4027914

  • Pediatric neurosurgical implications of the amniotic band disruption complex. Case reports and review of the literature. Pediatric neuroscience Hudgins, R. J., Edwards, M. S., Ousterhout, D. K., Golabi, M. 1985; 12 (4-5): 232-239

    Abstract

    Defects caused by the amniotic band disruption complex (ABDC) may vary from simple malformations caused by digital constriction to major scalp, craniofacial, and visceral malformations. ABDC may cause 7-14% of stillbirths. The etiology is unclear, but the most commonly accepted mechanism involves rupture of the amnion followed by fetal malformation, deformation, and compression. This mechanism does not adequately explain all anomalies such as hydrocephalus and holoprosencephaly that are seen in the ABDC. The use of prenatal ultrasound has allowed the diagnosis of the ABDC in utero. Since 1980, four children with the ABDC who required neurosurgical intervention were seen at the University of California, San Francisco; the presentation and subsequent surgical treatment of 2 of these children are discussed. A combined craniofacial team approach to the management of these children can maximize reconstructive and neurologic outcome.

    View details for PubMedID 3039476

  • STAGING OF CEREBRAL HEMISPHERIC TUMORS CANCER Edwards, M. S., Klein, D. M. 1985; 56 (7): 1784-1785

    Abstract

    There is currently no adequate staging system for cerebral astrocytomas. A scheme for acquiring data that can be used to stage cerebral hemisphere tumors is suggested. This data base, in conjunction with treatment and survival information, may be useful in the management of childhood hemispheric tumors.

    View details for Web of Science ID A1985AQR3200009

    View details for PubMedID 4027910

  • TUMOR-MARKERS AND CYTOLOGIC FEATURES OF CEREBROSPINAL-FLUID CANCER Edwards, M. S., Davis, R. L., Laurent, J. P. 1985; 56 (7): 1773-1777

    Abstract

    Tumor markers are useful in establishing the diagnosis of certain central nervous system tumors, especially germinal tumors of the pineal region. They are not sufficiently specific to be able to replace biopsy for exact diagnosis. They may also be useful for monitoring of therapy, as an indicator of recurrence of the tumor. Cerebrospinal fluid cytology is not generally useful in establishing a specific histologic diagnosis, especially in children, but can help to monitor therapy and predict tumor recurrence. More extensive studies are needed in both areas to define more precisely the role of markers and cytologic studies.

    View details for Web of Science ID A1985AQR3200007

    View details for PubMedID 2992748

  • A NONMALIGNANT TERATOMA SECRETING HCG - EXPANDING THE SPECTRUM OF ECTOPIC HORMONE PRODUCTION JOURNAL OF PEDIATRICS Lippe, B. M., Edwards, M. S., Braunstein, G. D., HALKSMILLER, M. 1984; 105 (5): 765-768

    View details for Web of Science ID A1984TR54000016

    View details for PubMedID 6389808

  • SURGICAL-TREATMENT OF SYRINGOMYELIA - FAVORABLE RESULTS WITH SYRINGOPERITONEAL SHUNTING JOURNAL OF NEUROSURGERY Barbaro, N. M., Wilson, C. B., Gutin, P. H., Edwards, M. S. 1984; 61 (3): 531-538

    Abstract

    The authors reviewed the clinical findings, radiological evaluation, and operative therapy of 39 patients with syringomyelia. Syringoperitoneal (SP) shunting was used in 15 patients and other procedures were used in 24 patients. Follow-up periods ranged from 1 1/2 to 12 years. During the period of this study, metrizamide myelography in conjunction with early and delayed computerized tomography scanning replaced all other diagnostic procedures in patients with syringomyelia. Preoperative accuracy for the two procedures was 87%. The most common symptoms were weakness (79%), sensory loss (67%), pain (38%), and leg stiffness (28%). Surgery was most effective in stabilizing or alleviating pain (100%), sensory loss (81%), and weakness (74%); spasticity, headache, and bowel or bladder dysfunction were less likely to be reversed. Approximately 80% of patients with idiopathic and posttraumatic syringomyelia and 70% of those with arachnoiditis improved or stabilized. Better results were obtained in patients with less severe neurological deficits, suggesting the need for early operative intervention. A higher percentage of patients had neurological improvement with SP shunting than with any other procedure, especially when SP shunting was the first operation performed. Patients treated with SP shunts also had the highest complication rate, most often shunt malfunction. These results indicate that SP shunting is effective in reversing or arresting neurological deterioration in patients with syringomyelia.

    View details for Web of Science ID A1984TG60100014

    View details for PubMedID 6747690

  • USE OF THE ARGON SURGICAL LASER IN NEUROSURGERY JOURNAL OF NEUROSURGERY Powers, S. K., Edwards, M. S., Boggan, J. E., Pitts, L. H., Gutin, P. H., Hosobuchi, Y., Adams, J. E., Wilson, C. B. 1984; 60 (3): 523-530

    Abstract

    The argon surgical laser has been used in 68 neurosurgical procedures that included the removal of intracranial and intraspinal tumors, spinal cord fenestration for syringomyelia, and the production of dorsal root entry zone lesions. Characteristics that make the argon surgical laser a useful microneurosurgical instrument include the availability of a fiberoptic delivery system, a laser spot size that can be varied continuously between 0.15 and 1.5 mm, a single laser-aiming and treatment beam, the transmission of argon laser light through aqueous media such as irrigating or cerebrospinal fluids, and improved hemostasis compared to conventional techniques. The argon laser is limited primarily by its relatively low power output (less than 16 W), which makes the excision of large tumors difficult. However, even with these limitations, which can be used to advantage in the proper setting, the authors' laboratory and clinical experience suggests that the argon surgical laser may be useful in certain microneurosurgical operations.

    View details for Web of Science ID A1984SF26300011

    View details for PubMedID 6538225

  • DISTRIBUTION OF HEMATOPORPHYRIN DERIVATIVE IN THE RAT 9L GLIOSARCOMA BRAIN-TUMOR ANALYZED BY DIGITAL VIDEO FLUORESCENCE MICROSCOPY JOURNAL OF NEUROSURGERY Boggan, J. E., Walter, R., Edwards, M. S., BORCICH, J. K., Davis, R. L., Koonce, M., Berns, M. W. 1984; 61 (6): 1113-1119

    Abstract

    A digital video fluorescence microscopy technique was used to evaluate the distribution of hematoporphyrin derivative (HPD) in the rat intracerebral 9L gliosarcoma brain-tumor model at 4, 24, 48, and 72 hours after intravenous administration of 10 mg/kg of the drug. Compared to surrounding normal brain, there was significant preferential uptake of HPD into the tumor. In sections surveyed, fluorescence reached a maximum value by 24 hours; however, only 33% to 44% of the tumor was fluorescent. In contrast, fluorescence within the surrounding normal brain was maximum at 4 hours, but was present in less than 1% of the brain tissue evaluated. The effect of HPD sensitization to a laser light dose (633 nm) of 30 joules/sq cm delivered through the intact skull was evaluated histologically in 10 rats. A patchy coagulation necrosis, possibly corresponding to the distribution of HPD fluorescence seen within the tumor, was observed. There was evidence that photoradiation therapy (PRT) affects defective tumor vasculature and that a direct tumor cell toxicity spared normal brain tissue. Despite these findings, limited uptake of HPD in tumor and the brain adjacent to tumor may decrease the effectiveness of PRT in the 9L gliosarcoma brain-tumor model. Because of the similarity between the capillary system of the 9L tumor and human brain tumors, PRT may have a limited therapeutic effect in patients with malignant brain tumors.

    View details for Web of Science ID A1984TT89800017

    View details for PubMedID 6239014

  • COMPUTERIZED-TOMOGRAPHY OF CRANIAL SUTURES .1. COMPARISON OF SUTURE ANATOMY IN CHILDREN AND ADULTS JOURNAL OF NEUROSURGERY Furuya, Y., Edwards, M. S., Alpers, C. E., Tress, B. M., Ousterhout, D. K., Norman, D. 1984; 61 (1): 53-58

    Abstract

    Knowledge of normal suture anatomy and development is vital in order to understand abnormal suture development and to be able to distinguish sutures radiographically from normal anatomical structures and possible skull fractures. The anatomy of the sutures and synchondroses of 150 normal pediatric and adult patients was studied using high-resolution computerized tomography scanning. Sutures of both the calvaria and skull base were most accurately identified in axial and coronal high-resolution thin-section scans when bone window algorithms were used. Developmental changes of the sutures and synchodroses , the inner and outer tables, and the diploic space were all well delineated. Vault sutures could be identified routinely in children, but their presence in adults varied considerably. With increasing age, parasutural sclerosis developed and sutures were more closely apposed.

    View details for Web of Science ID A1984SY06900009

    View details for PubMedID 6726411

  • CORRECTION OF CONGENITAL HYDROCEPHALUS INUTERO .2. EFFICACY OF INUTERO SHUNTING JOURNAL OF PEDIATRIC SURGERY Glick, P. L., Harrison, M. R., HALKSMILLER, M., Adzick, N. S., Nakayama, D. K., Anderson, J. H., Nyland, T. G., Villa, R., Edwards, M. S. 1984; 19 (6): 870-881

    Abstract

    To study the effect of in utero ventricular decompression of hydrocephalus on brain development and prognosis, and to evaluate the function and possible complications of different shunt designs, we created fetal hydrocephalus in 28 fetal lambs and 17 fetal monkeys by injecting kaolin into the cisterna magna during the third trimester. One fetal lamb had indwelling intracranial subdural and amniotic cavity pressure catheters placed to study serial changes in the relationship of intracranial pressure (ICP) and amniotic fluid pressure (AFP) from the time of injection until term. Twenty hydrocephalic fetal lambs underwent ventricular decompression--ventriculoamniotic (V-A), N = 10; ventriculo-right atrial (V-RA), N = 9; and ventriculo-pleural (V-PL), N = 1--21 to 25 days after the kaolin was injected; seven hydrocephalic fetuses were left unshunted as controls (CON). Eight fetal monkeys underwent V-A decompression 14 to 21 days after kaolin injection; nine were left unshunted as controls. All animals were delivered by cesarean section near term, assessed for viability and their brains examined grossly and microscopically. After kaolin injection in the fetal lamb, ICP (r = 0.94) and ICP minus AFP (r = 0.93) rose in a linear fashion, while AFP showed no trend (r = 0.22). All unshunted newborn lambs and monkeys had split sutures, dilated ventricles, and thinned cortical mantle. Most shunted lambs showed anatomic improvement with decreased head circumference, overriding sutures, normal-sized ventricles, and improved survival. However, histopathology revealed marked white matter destruction. In contrast, most shunted monkeys showed little anatomic improvement. Both shunted and unshunted monkey brains showed a severe inflammatory ventriculitis. In both lambs and monkeys, shunting was associated with a variety of complications including subdural hematoma, subdural hygroma, shunt infection, shunt occlusion, and improper shunt tip placement. In this experimental model, in utero decompression of obstructive hydrocephalus improves overall survival, improves gross ventriculomegaly, does not improve histopathologic brain damage, and is associated with significant complications. The choice of the optimal shunt design and the effect on postnatal neurologic function requires further study. This work emphasizes the need for continuing research in an animal model prior to human application.

    View details for Web of Science ID A1984TV42200046

    View details for PubMedID 6542937

  • EFFECT OF MICROSURGICAL AND CARBON-DIOXIDE AND ARGON-LASER RESECTION ON RECURRENCE OF THE INTRACEREBRAL 9L RAT GLIOSARCOMA NEUROSURGERY Edwards, M. S., Boggan, J. E., BOLGER, C. A., Davis, R. L. 1984; 14 (1): 52-56

    Abstract

    The intracerebral 9L rat brain tumor was resected from 38 rats with the use of standard microsurgical techniques, the carbon dioxide laser, or the argon laser. The extent of resection was evaluated by histological examination, and the effect on survival of the three methods was compared. All three methods achieved histologically verifiable gross total resection, and tumor recurrence after resection by all three methods occurred at the same rate.

    View details for Web of Science ID A1984RY91600010

    View details for PubMedID 6420723

  • HEMATOPORPHYRIN DERIVATIVE PHOTORADIATION THERAPY OF THE RAT 9L GLIOSARCOMA BRAIN-TUMOR MODEL LASERS IN SURGERY AND MEDICINE Boggan, J. E., Edwards, M. S., Berns, M. W., Walter, R. J., BOLGER, C. A. 1984; 4 (1): 99-105

    Abstract

    The distribution of hematoporphyrin derivative (HPD) in the rat 9L gliosarcoma intracerebral brain tumor model at 4, 24, 48, and 72 hours after intravenous administration was evaluated using a digital video fluorescence microscopy technique. Maximum tissue fluorescence in the normal brain was observed at 4 hours, whereas maximum fluorescence in the tumor regions occurred at 24 hours. Although the fluorescence counts suggested that there was significant uptake of HPD within the tumors when compared to normal brain, only 33% to 44% of each of the eight tumors surveyed showed fluorescence. In response to a laser light dose (633 nm) of 30 J/cm2, six rats that had been sensitized with HPD had a patchy coagulation necrosis involving up to 70% of the total tumor volume. In contrast, four rats given HPD only or exposed to laser only had no areas of necrosis, as observed on histological examination. In a group of 30 rats, no prolongation of survival was observed in response to photoradiation therapy.

    View details for Web of Science ID A1984TZ99400013

    View details for PubMedID 6235423

  • MANAGEMENT OF VENTRICULOMEGALY IN THE FETUS JOURNAL OF PEDIATRICS Glick, P. L., Harrison, M. R., Nakayama, D. K., Edwards, M. S., Filly, R. A., Chinn, D. H., Callen, P. W., Wilson, S. L., Golbus, M. S. 1984; 105 (1): 97-105

    Abstract

    We studied 24 human fetuses with cerebral ventriculomegaly by serial obstetric ultrasound to define the natural history of fetal ventricular enlargement and to develop a management strategy. In 10 fetuses, ventriculomegaly was associated with other severe anomalies; nine of these families chose to terminate the pregnancy. In three other severely affected fetuses in whom ventriculomegaly was detected serendipitously late in gestation, routine obstetrical management was performed; none survived. Eleven fetuses had ventriculomegaly without associated severe anomalies. Ventriculomegaly remained stable or of moderate severity throughout gestation in nine, resolved gradually in one, and progressed in one who did not have signs of increased intracranial pressure at birth. All of these fetuses were viable; three patients required shunting in the neonatal period, and two others by 5 months of age. Although obstetric ultrasound usually can detect anomalies associated with fetal ventriculomegaly, three fetuses with isolated ventriculomegaly had midline brain malformations that could not be distinguished in utero from hydrocephalus, even in retrospect. Prenatal diagnosis improves perinatal management by allowing counseling, and selective pregnancy termination, or selection of the timing, mode, and place of delivery to optimize outcome. Most fetuses with ventriculomegaly do not require intervention before birth.

    View details for Web of Science ID A1984TA64300023

    View details for PubMedID 6737155

  • ACUTELY THROMBOSED ANEURYSM OF THE MIDDLE CEREBRAL-ARTERY PRESENTING AS INTRACRANIAL HEMORRHAGE IN A 3-YEAR-OLD CHILD - CASE-REPORT JOURNAL OF NEUROSURGERY Andrews, B. T., Edwards, M. S., Gannon, P. 1984; 60 (6): 1303-1307

    Abstract

    Spontaneous thrombosis of aneurysms occurs rarely in children, and, to our knowledge, there are no reports of aneurysms presenting as an embolic event in a child. We describe the case of a 3-year-old boy whose symptoms initially suggested an ischemic event to the dominant hemisphere. Initial computerized tomography scans indicated an intracranial hemorrhage. Subsequent radiographic study revealed evidence of emboli and, at exploration, a large acutely thrombosed aneurysm of the left middle cerebral artery associated with arterial occlusion was found. Entrapment of the aneurysm and thrombectomy provided excellent operative results.

    View details for Web of Science ID A1984ST72400031

    View details for PubMedID 6726376

  • PHASE-II EVALUATION OF DIBROMODULCITOL IN THE TREATMENT OF RECURRENT MEDULLOBLASTOMA, EPENDYMOMA, AND MALIGNANT ASTROCYTOMA JOURNAL OF NEUROSURGERY Levin, V. A., Edwards, M. S., Gutin, P. H., VESTNYS, P., Fulton, D., Seager, M., Wilson, C. B. 1984; 61 (6): 1063-1068

    Abstract

    The authors have conducted a Phase II trial to evaluate orally administered dibromodulcitol in the treatment of 40 evaluable patients with recurrent medulloblastoma, ependymoma, and malignant astrocytoma. Ten of 20 patients harboring medulloblastoma responded to therapy with a median time to tumor progression (MTP) of 40 weeks, and four of 20 patients had no sign of progression of disease 4 years after treatment was begun. The MTP for all 12 patients with ependymoma was 30 weeks. Nine of these 12 patients had stabilization of their disease with an MTP of 67 weeks; three of these 12 patients had no signs of progression for 1 to 3 years after treatment was begun. Of six patients harboring supratentorial gliomas, none responded to dibromodulcitol. Two patients, one with a primitive neuroectodermal tumor and the other with a metastatic carcinoma of the breast, had stabilization of disease for more than 4 and 2 years, respectively.

    View details for Web of Science ID A1984TT89800009

    View details for PubMedID 6502234

  • PAIN RELIEF FROM DORSAL-ROOT ENTRY ZONE LESIONS MADE WITH ARGON AND CARBON-DIOXIDE MICROSURGICAL LASERS JOURNAL OF NEUROSURGERY Powers, S. K., Adams, J. E., Edwards, M. S., Boggan, J. E., Hosobuchi, Y. 1984; 61 (5): 841-847

    Abstract

    Argon and carbon dioxide microsurgical lasers were used to produce lesions in the dorsal root entry zone (DREZ) experimentally in six cats and surgically in 21 patients who had denervation pain syndromes. The technique of producing lesions, the histological and physiological changes seen in the cat spinal cord, and the results of treatment in the clinical series are discussed. Lesions were produced within the DREZ without new involvement of the dorsal column system or corticospinal tract in all but one patient. Based on their subjective evaluation, two-thirds of the patients were relieved of more than 50% of their preoperative pain. These experimental results and clinical experience suggest that the argon and carbon dioxide lasers effectively produce localized microsurgical lesions in the DREZ. The concept that an abnormality involving either neurons in the substantia gelatinosa or internuncial fibers in Lissauer's tract is responsible for pain in patients with primary sensory nerve deafferentation is discussed.

    View details for Web of Science ID A1984TP76500004

    View details for PubMedID 6436446

  • MISONIDAZOLE NEUROTOXICITY IN RATS .1. EVALUATION OF MISONIDAZOLE NEUROTOXICITY IN RATS BY ANALYSIS OF BRAIN-STEM AUDITORY AND CORTICAL EVOKED-POTENTIALS JOURNAL OF NEURO-ONCOLOGY Edwards, M. S., Gordon, D. G., Levin, V. A., Phillips, T. L. 1984; 2 (2): 91-94

    Abstract

    The effects of misonidazole (MISO) on brain stem evoked potentials (BAEPs) and cortical evoked potentials (CEPs) were evaluated in 16 Sprague-Dawley rats treated with the agent. As found in previous studies, serial BAEP values were diagnostic of the onset of MISO toxicity before clinical signs and symptoms appeared. However, MISO had no effects on CEPs, which remained essentially unchanged through the course of the experiment. At histologic examination, significant changes were found in the area of the brain stem, but there was no histologic evidence of damage to cortical or subcortical structures caused by MISO administration. The results of this study suggest that the neurotoxic effects of MISO are species-specific, and that while the rat model may be useful for comparison of the relative toxic effects of nitroimidazole radiosensitizers, it is not a model suited for measurement of neurotoxicity caused by MISO in humans and nonhuman primates.

    View details for Web of Science ID A1984SW26800001

    View details for PubMedID 6481428

  • COMPUTERIZED-TOMOGRAPHY OF CRANIAL SUTURES .2. ABNORMALITIES OF SUTURES AND SKULL DEFORMITY IN CRANIOSYNOSTOSIS JOURNAL OF NEUROSURGERY Furuya, Y., Edwards, M. S., Alpers, C. E., Tress, B. M., Norman, D., Ousterhout, D. K. 1984; 61 (1): 59-70

    Abstract

    Preoperative computerized tomographic (CT) scans of 24 children who had surgery for either single or multiple craniosynostoses were compared with skull radiographs and operative and pathological findings. In addition to providing accurate imaging of calvarial and skull base deformities secondary to premature suture closure, high-resolution CT with bone definition algorithms supplied valuable detail of anatomical changes at the abnormally developed suture. The CT findings varied with the location of the suture. Thickened bony ridges predominated at the sagittal suture, focal bone thickening and erosions were more likely to be found at the metopic suture, and parasutural sclerosis was the prevalent finding on one side of the lambdoid suture. No evidence of the suture could be detected in the majority of patients with complete coronal craniosynostosis. Radiographs of the skull were shown to be a relatively insensitive means of imaging the zone of limited fusion, especially the lambdoid suture. An excellent correlation was found between the CT scan and the operative and pathological findings. There was histological evidence of progressive suture fusion in virtually all patients. An asymmetrically narrowed lucent zone with parasutural sclerosis or bony ridges seen on CT scans correlated well with fibrous union of the suture found on histological examination. The authors conclude that high-definition CT used in conjunction with bone windows and thin and coronal slices for the evaluation of sagittal sutures is a useful imaging method for the evaluation of craniosynostosis.

    View details for Web of Science ID A1984SY06900010

    View details for PubMedID 6726412

  • ARGON-LASER SURGERY OF PEDIATRIC NEURAL NEOPLASMS CHILDS BRAIN Edwards, M. S., Boggan, J. E. 1984; 11 (3): 171-175

    Abstract

    The argon microsurgical laser offers a less traumatic and often more hemostatic technique for the ablation of neural and tumor tissues. Our experience in 15 microsurgical procedures is discussed. The argon laser was essential in the removal of small, moderately vascular, strategically placed intracranial and spinal lesions. In each of these cases, the laser either permitted a complete resection or augmented the amount of tumor resected over that which could be removed by standard microsurgical technique. The laser was not beneficial in operations on large lesions or those with markedly increased blood flow. There were no early or late complications related to the use of the argon laser. Further advances in laser technology will afford significant improvements over the presently available techniques of laser microneurosurgery.

    View details for Web of Science ID A1984SQ72100003

    View details for PubMedID 6723434

  • SUPRATENTORIAL MALIGNANT GLIOMAS OF CHILDHOOD - RESULTS OF TREATMENT WITH RADIATION-THERAPY AND CHEMOTHERAPY JOURNAL OF NEUROSURGERY Phuphanich, S., Edwards, M. S., Levin, V. A., VESTNYS, P. S., Wara, W. M., Davis, R. L., Wilson, C. B. 1984; 60 (3): 495-499

    Abstract

    Twenty-seven patients aged 1 to 18 years harboring supratentorial (20 in the cerebrum and seven in the thalamus) malignant gliomas were treated between 1975 and 1982. There were four glioblastomas multiforme, 14 anaplastic astrocytomas, and nine malignant gliomas. All patients had a subtotal resection or biopsy as the initial procedure and received postoperative radiation therapy (RT). Fifteen of 27 patients were treated by RT alone; 14 had tumor progression with a median time to tumor progression (MTP) of 65 weeks. Twelve patients were treated with chemotherapy as an adjuvant to RT; only seven had tumor recurrence, with an MTP of 130 weeks. Of the 21 patients with recurrent tumors in both groups, 18 were treated with chemotherapy alone, or chemotherapy with a second surgical procedure or second course of RT. For all histological grades of tumor, the MTP for first recurrence was 75 weeks and the median survival time was 180 weeks. Age at initial diagnosis was found to be a statistically significant prognostic factor, with patients younger than 10 years of age surviving longer than patients aged over 10 years (p = 0.02).

    View details for Web of Science ID A1984SF26300006

    View details for PubMedID 6699693

  • 5-FLUOROURACIL AND 1-(2-CHLOROETHYL)-3-CYCLOHEXYL-1-NITROSOUREA (CCNU) FOLLOWED BY HYDROXYUREA, MISONIDAZOLE, AND IRRADIATION FOR BRAIN-STEM GLIOMAS - A PILOT-STUDY OF THE BRAIN-TUMOR RESEARCH-CENTER AND THE CHILDRENS CANCER GROUP NEUROSURGERY Levin, V. A., Edwards, M. S., Wara, W. M., Allen, J., Ortega, J., VESTNYS, P. 1984; 14 (6): 679-681

    Abstract

    Twenty-eight evaluable children with the diagnosis of brain stem glioma were treated with 5-fluorouracil and CCNU before posterior fossa irradiation (5500 rads); during irradiation, the children received hydroxyurea and misonidazole. The treatment was well tolerated, and minimal toxicity was produced. The median relapse-free survival was 32 weeks, and the median survival was 44 weeks. Analysis of covariates showed that, in patients between the ages of 2 and 19 years, survival was longest in the older children (P less than 0.02). Tumor histology, sex, extent of operation (if any), Karnofsky score, and radiation dose did not correlate with survival.

    View details for Web of Science ID A1984TB47300006

    View details for PubMedID 6087193

  • MISONIDAZOLE NEUROTOXICITY IN RATS .2. EFFECT OF PRETREATMENT AND INTERMITTENT TREATMENT WITH PENTOBARBITAL ON MISONIDAZOLE NEUROTOXICITY IN THE RAT JOURNAL OF NEURO-ONCOLOGY Edwards, M. S., Gordon, D. G., SALAMY, A., Levin, V. A., Phillips, T. L. 1984; 2 (2): 95-98

    Abstract

    Rats pretreated for 5 days with 50 mg/kg of pentobarbital tolerated statistically significant higher doses of misonidazole before the onset of misonidazole-induced neurotoxicity than rats treated intermittently with the same dose of pentobarbital. Presumably in pretreated rats, pentobarbital induced an increase in the activities of hepatic microsomal enzymes that led to a more rapid metabolism of misonidazole than in rats treated only intermittently.

    View details for Web of Science ID A1984SW26800002

    View details for PubMedID 6481429

  • KAOLIN-INDUCED CONGENITAL HYDROCEPHALUS INUTERO IN FETAL LAMBS AND RHESUS-MONKEYS JOURNAL OF NEUROSURGERY Edwards, M. S., Harrison, M. R., HALKSMILLER, M., Nakayama, D. K., Berger, M. S., Glick, P. L., Chinn, D. H. 1984; 60 (1): 115-122

    Abstract

    A model of congenital hydrocephalus in utero in fetal lambs and rhesus monkeys has been produced by the intracisternal injection of kaolin. Initial attempts to produce hydrocephalus using silicone oil were unrewarding. Hydrocephalus had developed by 2 weeks post-injection and could be followed by ultrasonography. The pathological findings were similar to those reported using kaolin in other species. Ventriculoamniotic shunting, when successful, was capable of partially reversing the deleterious effects of hydrocephalus. The major drawback of the present model is that hydrocephalus is produced during the second rather than the first trimester of pregnancy. However, kaolin produces mainly an obstructive hydrocephalus without other associated brain or systemic anomalies.

    View details for Web of Science ID A1984RX32800017

    View details for PubMedID 6537789

  • EVALUATION OF DESMETHYLMISONIDAZOLE-INDUCED NEUROTOXICITY IN THE RAT USING BRAIN-STEM AUDITORY EVOKED-POTENTIALS INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Edwards, M. S., Gordon, D. G., Levin, V. A. 1984; 10 (8): 1377-1379

    Abstract

    Brainstem auditory evoked responses (BAEPs) and a scale that evaluates clinical signs of neurotoxicity were used to measure the onset of neurotoxic effects seen in rats after chronic injection of 400 mg/kg/day of the radiosensitizer desmethylmisonidazole (DMM) for 5 days/week for 7 weeks. A significant neurotoxic effect was indicated by increases in the latencies of peaks 4 and 5 of the BAEP after the 24th injection of DMM; clinical signs of neurotoxicity were observed after the 30th injection. Histologic examination of brainstems from rats sacrificed after selected number of injections during treatment showed that the onset of lesions in the brainstem was gradual but not extensive. Pentobarbital used as an anesthetic agent had no effect on the induction of neurotoxicity.

    View details for Web of Science ID A1984TJ54000042

    View details for PubMedID 6469760

  • Chemotherapy of recurrent pediatric posterior fossa tumors. Clinical neurosurgery Edwards, M. S., Levin, V. A., Wilson, C. B. 1983; 30: 209-225

    View details for PubMedID 6667576

  • HYDROCEPHALUS IN ADULTS - ULTRASOUND DETECTION THROUGH SURGICALLY CREATED CRANIAL DEFECTS RADIOLOGY Gooding, G. A., Edwards, M. S. 1983; 148 (2): 561-562

    Abstract

    For 15 men who had undergone neurosurgery, ultrasound of the brain through the surgically created cranial defects identified the status of the ventricles in 15 of 17 total examinations (88%). Two failures involved patients with cranial defects in the frontal region. Assessments were all correct when correlated with computed tomography.

    View details for Web of Science ID A1983QZ62300042

    View details for PubMedID 6867357

  • Evoked potentials in rats with misonidazole neurotoxicity. II. Somatosensory evoked potentials. Journal of neuro-oncology Powers, S. K., Edwards, M. S., Baringer, R. A. 1983; 1 (2): 125-130

    Abstract

    Spinal and cortical somatosensory potentials were recorded weekly in rats treated with misonidazole at a dose of 300 mg/kg/day until clinical signs of severe neurotoxicity developed. After sacrifice, the brains, spinal cords and sciatic nerves were examined. All treated rats developed necrotic brain stem lesions identical to those previously described by Griffin and by us. Two rats had mild demyelination of spinal cord white matter tracts, but only one of these rats had changes in the SEPs. Interestingly, changes in the cervical and cortical SEP from this rat were only transient. We conclude that misonidazole neurotoxicity in the rat predominantly affects the brain stem nuclei adjacent to the fourth ventricle without involving the lemniscal pathways that are situated ventromedially in the brain stem. Therefore, somatosensory evoked potentials (SEPs) are not useful for the diagnosis of MISO neurotoxicity.

    View details for PubMedID 6678964

  • DIAGNOSIS OF ACUTE NERVE COMPRESSION IN THE CAT WITH HIGH-FREQUENCY NERVE TRAINS EVOKED-RESPONSES NEUROSURGERY Edwards, M. S., BOLGER, C. A., Jewett, D. L. 1983; 12 (1): 1-6

    Abstract

    High frequency nerve trains were evaluated from above and below the site of compression before, during, and after acute compression of the sciatic nerves of six adult cats. Acute nerve compression reduced the ability of axons to conduct high frequency impulse trains: the longer the compression, the lower the frequency of impulses that could be conducted through the region of compression without a decrement in latency and amplitude. Possible mechanisms for alterations of nerve trains and the possible clinical and experimental use of nerve trains analysis are discussed.

    View details for Web of Science ID A1983QA24400001

    View details for PubMedID 6828211

  • IMPROVEMENT IN SURVIVAL PRODUCED BY SEQUENTIAL THERAPIES IN THE TREATMENT OF RECURRENT MEDULLOBLASTOMA CANCER Levin, V. A., VESTNYS, P. S., Edwards, M. S., Wara, W. M., Fulton, D., Barger, G., Seager, M., Wilson, C. B. 1983; 51 (8): 1364-1370

    Abstract

    Thirty-six patients with recurrent medulloblastoma were treated with various combination chemotherapy protocols after initial treatment (usually irradiation) failed. Use of systemic chemotherapy was limited by depressed bone marrow reserves secondary to previous craniospinal irradiation. Intraventricular and intrathecal therapies included cytosine arabinoside (Ara-C), methotrexate, and thio-tepa given as single agents. Major systemic agents used alone or in combination included CCNU, procarbazine, vincristine, and the hexitol epoxides. Patients were reirradiated with or without misonidazole when there was definite tumor progression after all other therapies failed and/or because myelosuppression was so severe that further chemotherapy was not possible. Sequential systemic or intrathecal chemotherapy and reirradiation produced median survivals of two years and 25% quartile survivals of 2.9 years. The prognosis for patients harboring recurrent medulloblastoma has improved considerably over the years because of the therapeutic approaches reported here.

    View details for Web of Science ID A1983QH38500007

    View details for PubMedID 6687443

  • PEDIATRIC BRAIN-STEM TUMORS - RADIOGRAPHIC, PATHOLOGICAL, AND CLINICAL CORRELATIONS NEUROSURGERY Berger, M. S., Edwards, M. S., LAMASTERS, D., Davis, R. L., Wilson, C. B. 1983; 12 (3): 298-302

    Abstract

    A retrospective analysis of the case histories of 21 pediatric patients (ages, 2.5 to 18 years) with a histologically proven diagnosis of brain stem glioma was performed to determine whether patterns of radiographic appearance could be correlated with pathology. Based on the computed tomographic or pneumoencephalographic appearance of the tumor at the time of clinical diagnosis, tumors were divided into four types: central intrinsic (Type I), central exophytic expansion into the 4th ventricle (Type II), eccentric exophytic expansion not involving the 4th ventricle (Type III), and both eccentric and central exophytic expansion (Type IV). Regardless of the radiographic classification, all patients except one, who harbored a well-differentiated astrocytoma in the area of the pons, had an anaplastic astrocytoma (n = 14) or a glioblastoma multiforme (n = 6). There was no appreciable difference in survival between patients with either tumor histology. The presence of a cystic component did not affect survival. High resolution computed tomographic scans, with reconstructed images of the posterior fossa, can predict the presence and location of brain stem tumors and associated cysts and probably the histological nature of the tumor.

    View details for Web of Science ID A1983QH97800008

    View details for PubMedID 6302553

  • PRIMARY CEREBRAL NEURO-BLASTOMA - LONG-TERM FOLLOW-UP REVIEW AND THERAPEUTIC GUIDELINES JOURNAL OF NEUROSURGERY Berger, M. S., Edwards, M. S., Wara, W. M., Levin, V. A., Wilson, C. B. 1983; 59 (3): 418-423

    Abstract

    Primary cerebral neuroblastoma is a distinct pathological and clinical entity that differs from other primitive neuroectodermal tumors. To characterize the clinical course of this lesion, the authors performed a retrospective analysis in 11 patients who ranged in age from 17 months to 26 years. The tumor had no predilection for either sex. Signs and symptoms were mostly those associated with increased intracranial pressure. The lesions commonly involved the parietal and occipital lobes. Computerized tomography scans of nine patients showed five solid and four cystic lesions; calcifications were found more commonly in the solid lesions. Contrast enhancement was seen in all tumors, yet angiograms typically showed an avascular mass. Total removal of tumor was possible in only two patients, both with cystic tumors. The remaining nine underwent subtotal resection of a solid lesion (in five) or a cystic lesion (in four). All 11 patients underwent postoperative irradiation that included the spinal axis in two cases; only one received adjuvant chemotherapy (solid tumor). Four patients, all with solid tumors that initially were subtotally resected, had evidence of tumor recurrence. The only patient with a subtotally resected solid lesion who did not have recurrence received adjuvant chemotherapy. The six patients who had cystic lesions are free of recurrent tumor at 26 to 109 months after surgery. Based on follow-up analysis of the 11 patients, recommendations are proposed for the treatment of primary cerebral neuroblastomas.

    View details for Web of Science ID A1983RF00200007

    View details for PubMedID 6886755

  • THE LASER IN NEUROLOGICAL SURGERY JOURNAL OF NEUROSURGERY Edwards, M. S., Boggan, J. E., FULLER, T. A. 1983; 59 (4): 555-566

    Abstract

    The use of lasers in neurosurgical procedures has received a great deal of attention recently. Surgical use of lasers has been viewed with suspicion and skepticism, probably because of (justified) apprehensions about the misuse of lasers in early work and about the ways in which laser light affects tissues, and a lack of understanding of the basic physics and practical operation of lasers. The authors review the physics, biophysics, experimental findings, and operative use of lasers in current neurosurgical practice, and discuss briefly their experience gained in over 150 neurosurgical procedures using the carbon dioxide and argon surgical lasers.

    View details for Web of Science ID A1983RJ64700001

    View details for PubMedID 6350538

  • COMPUTERIZED-TOMOGRAPHY OF PERIPHERAL-NERVE LESIONS JOURNAL OF NEUROSURGERY Powers, S. K., Norman, D., Edwards, M. S. 1983; 59 (1): 131-136

    Abstract

    Nine patients with a peripheral nerve lesion (six intrinsic and three extrinsic) were evaluated with computerized tomography (CT). In all but one instance, the CT scans gave useful information regarding the anatomical location, size, and relationship of the lesion to surrounding structures. These cases illustrate the usefulness of CT as a diagnostic tool in the evaluation of peripheral nerve lesions.

    View details for Web of Science ID A1983QW70800014

    View details for PubMedID 6306180

  • INTRAOPERATIVE REAL-TIME ULTRASOUND IN THE LOCALIZATION OF INTRACRANIAL NEOPLASMS RADIOLOGY Gooding, G. A., Edwards, M. S., RABKIN, A. E., Powers, S. K. 1983; 146 (2): 459-462

    Abstract

    Intraoperative ultrasound imaging in the localization of intracranial lesions in eight patients is described. This technique is effective in tumor location, and it can be used throughout surgery to monitor the extent of tumor resection. The ability to locate precisely a deeply situated intracranial lesion intraoperatively can reduce the risk of damage to normal tissue, assist in determining the extent of tumor resection, and reduce the time of surgery. Intraoperative ultrasound holds great promise, but if it is to be used to its fullest extent, further modifications of transducers must be developed.

    View details for Web of Science ID A1983PZ13800030

    View details for PubMedID 6849094

  • Evoked potentials in rats with misonidazole neurotoxicity. I. Brain stem auditory evoked potentials. Journal of neuro-oncology Edwards, M. S., Powers, S. K., Baringer, R. A., Jewett, D. L., Bolger, C., Phillips, T. L. 1983; 1 (2): 115-123

    Abstract

    Central neurotoxicity produced in rats by daily administration of 300 mg/kg of misonidazole (MISO) 5 times/week for 4-5 weeks (total dose = 6.0 gm/kg) was evaluated weekly wit brain stem auditory evoked potentials (BAEPs). Compared to untreated control rats, all treated rats had a prolongation of the I-IV interpeak latency (p less than 0.005) at a mean of 13.2 +/- 2.7 days at a cumulative dose of approximately 4.0 gm/kg of MISO per rat. In some rats, the I-III and I-II interwave latencies were prolonged and waves III and IV were lost. Control rats did not show any significant alteration in BAEP latency or amplitude. Histopathologic examination of the brain stems of treated rats showed that necrotic lesions were present primarily in the nuclei of the tegmentum of the fourth ventricle, with scattered nuclear involvement in the cerebellar roof nuclei, inferior olive, and nucleus of the spinal tract of the trigeminal nerve. The cerebral cortex appeared to be normal in all treated rats. Changes in BAEPs caused by central neurotoxicity correlated with the histopathologic findings. We conclude that BAEPs are a sensitive method for evaluating MISO central neurotoxicity in the rat model.

    View details for PubMedID 6678963

  • CORRECTION OF CONGENITAL HYDROCEPHALUS INUTERO .1. THE MODEL - INTRACISTERNAL KAOLIN PRODUCES HYDROCEPHALUS IN FETAL LAMBS AND RHESUS-MONKEYS JOURNAL OF PEDIATRIC SURGERY Nakayama, D. K., Harrison, M. R., Berger, M. S., Chinn, D. H., HALKSMILLER, M., Edwards, M. S. 1983; 18 (4): 331-338

    Abstract

    In the fetus with congenital hydrocephalus, obstruction to the flow of cerebrospinal fluid (CSF) results in ventricular dilation and neurologic impairment. Decompression of the obstructed ventricles before birth may ameliorate the damage and allow normal development to proceed. Although appealing, this pathophysiologic rationale has not been adequately tested because a satisfactory fetal model has not been available. We have developed a model of obstructive hydrocephalus in the fetal lamb and rhesus monkey by injecting kaolin into the cisterna magna through the posterior atlanto-occipital membrane early in the last trimester. Preliminary studies injecting silicone oil were unsuccessful. The development of fetal ventriculomegaly was followed using prenatal ultrasonography. Massive hydrocephalus developed in six sheep, three liveborn at term and three stillborn after premature vaginal delivery, and in 2 fetal rhesus monkeys. All treated animals had external signs of hydrocephalus with marked cranial enlargement. Neuropathologic examinations demonstrated fibrosis of the leptomeninges and subarachnoid spaces around the fourth ventricle. Dilation of the lateral and third ventricles resulted, with attenuation of the cerebral white matter. On histologic examination, the grey matter was relatively well preserved, while the white matter was severely attenuated. This model mimics the clinical and pathologic picture seen in human infants and should allow us to study the pathophysiology of congenital obstructive hydrocephalus and the efficacy and feasibility of its correction in utero.

    View details for Web of Science ID A1983RB35300001

    View details for PubMedID 6620070

  • INTRAVENTRICULAR HEMORRHAGE FOLLOWING VENTRICULOPERITONEAL SHUNT PLACEMENT - REAL-TIME ULTRASONOGRAPHIC DEMONSTRATION JOURNAL OF ULTRASOUND IN MEDICINE MAHONY, B. S., Gross, B. H., Callen, P. W., Filly, R. A., Edwards, M. S. 1983; 2 (3): 143-145

    View details for Web of Science ID A1983QG03000013

    View details for PubMedID 6842676

  • EVALUATION OF MISONIDAZOLE PERIPHERAL NEUROTOXICITY IN RATS BY ANALYSIS OF NERVE TRAINS EVOKED-RESPONSE INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Edwards, M. S., BOLGER, C. A., Levin, V. A., Phillips, T. L., Jewett, D. L. 1982; 8 (1): 69-74

    Abstract

    The clinical use of misonidazole and other nitroimidazole radiosensitizing agents is limited by the peripheral and central neurotoxicity that is produced in animals and humans. In a blinded study, rats treated with misonidazole at either 100 mg/kg or 300 mg/kg, 5 days/week for 3 weeks, were evaluated for peripheral neurotoxicity using nerve trains evoked responses. Only one rat treated at a dose of 100 mg/kg developed symptoms and signs of neurotoxicity, while all rats treated at 300 mg/kg developed these signs and symptoms. Nerve trains analysis made possible a diagnosis of neurotoxicity before overt clinical signs appeared. This test is non-invasive and may be useful for evaluating patients receiving nitroimidazole radiosensitizers as part of a radiation therapy regimen.

    View details for Web of Science ID A1982NC48800011

    View details for PubMedID 6277833

  • INTRATHECAL CYTOSINE-ARABINOSIDE FOR THE TREATMENT OF MENINGEAL METASTASES FROM MALIGNANT BRAIN-TUMORS AND SYSTEMIC TUMORS CANCER CHEMOTHERAPY AND PHARMACOLOGY Fulton, D. S., Levin, V. A., Gutin, P. H., Edwards, M. S., SEAGER, M. L., STEWART, J., Wilson, C. B. 1982; 8 (3): 285-291

    View details for Web of Science ID A1982PH50800007

    View details for PubMedID 6897022

  • HYPOGLOSSAL NEURILEMOMA - CASE-REPORT AND REVIEW OF THE LITERATURE NEUROSURGERY Berger, M. S., Edwards, M. S., BINGHAM, W. G. 1982; 10 (5): 617-620

    Abstract

    The case of a patient harboring a rare intracranial hypoglossal nerve sheath tumor is presented, and the literature concerning this lesion, especially with relation to age and sex patterns and the initial and presenting symptoms and signs, is reviewed. The importance of a thorough radiological examination with detailed vertebral angiography and contrast-enhanced computed tomographic scans of the hypoglossal canal is discussed. Based on our experience with this patient, we recommend total excision of this lesion.

    View details for Web of Science ID A1982PB81600013

    View details for PubMedID 7099413

  • COMPARISON OF THE BRAIN-TISSUE RESPONSE IN RATS TO INJURY BY ARGON AND CARBON-DIOXIDE LASERS NEUROSURGERY Boggan, J. E., Edwards, M. S., Davis, R. L., BOLGER, C. A., Martin, N. 1982; 11 (5): 609-616

    Abstract

    This study compares the acute and chronic response of brain tissue to injury by equal power density, focused argon (Ar) and carbon dioxide (CO2) laser beams. A cortical incision from 0.2-second laser pulses of 12.5 X 10(3) W/cm2 power density was made in the exposed cortex of 32 rats using either the CO2 or the Ar laser. The brains were examined at intervals from 1/2 hour to 1 month after injury. Histologically, all brain incisions were sharply demarcated hemispheroidal defects with a vaporized center bordered by a zone of coagulation necrosis surrounded by edema. The laser incisions were found to be of equal depth (less than 1 mm). The average cortical surface diameter of the CO2 laser incision was 0.86 mm for a focused beam spot size 0.45 mm in diameter, compared with 0.65 mm with the Ar laser, which had a focused beam spot size 0.15 mm in diameter. In both incisions, some delayed depth effect was observed. A progression of the tissue necrosis by approximately 17% was observed during the first 24 hours after injury. During the first 4 hours after injury, the Evans blue blood-brain barrier defect (EBBD) surrounding the cortical incisions averaged 5.80 mm2 for the CO2 incision and 0.888 mm2 for the Ar incision. In both types of brain incision, the EBBD appeared to resolve by 24 hours after injury. At 1 month after injury, a core of coagulation necrosis surrounded by mild fibrillary gliosis was observed. At the power density and focused beam spot sizes used, there was no significant difference in the overall brain tissue response to Ar and CO2 laser lesions.

    View details for Web of Science ID A1982PS81900004

    View details for PubMedID 6818490

  • SPINAL-CORD PATHWAYS MEDIATING SOMATOSENSORY EVOKED-POTENTIALS JOURNAL OF NEUROSURGERY Powers, S. K., BOLGER, C. A., Edwards, M. S. 1982; 57 (4): 472-482

    Abstract

    Using a CO2 laser, discrete thoracic spinal cord lesions were made in cats anesthetized with ketamine and xylazine (Rompun). Differences in cortical somatosensory evoked potentials (SEP's) produced with high-intensity stimulation (20 times the motor threshold) of each posterior tibial nerve determined for nine different combinations of unilateral spinal cord lesions. The results of these studies show that nerve fibers in the ipsilateral dorsal column, the ipsilateral dorsal spinocerebellar tract, and the contralateral ventrolateral tracts with respect to the side of leg stimulation, contribute to cortical SEP's. A lesion of the dorsal spinocerebellar tract affected only the early waves (less than 30 msec) of the SEP from leg stimulation ipsilateral to the side of the lesion, whereas a solitary lesion of the ventrolateral tract caused changes primarily in the amplitude of later waves (greater than 30 msec) of the SEP produced by contralateral leg stimulation. Lesions involving one-half of the dorsal column caused changes in the amplitude of both the early and late waves produced by stimulation ipsilateral to the side of the lesion. The effects of various combinations of lesions on the cortical SEP's were not additive, which indicates significant interaction between afferent pathways. These findings suggest that high-intensity peripheral nerve stimulation, which activates both C and A fibers, could be used intraoperatively to assess spinal cord function with more accuracy than the current practice of using a stimulus strength of twice the motor threshold. The importance of using anesthetic agents that do not depress cortical activity (which may affect the later components of the SEP) is also emphasized.

    View details for Web of Science ID A1982PJ49700006

    View details for PubMedID 7108596

  • PROPHYLAXIS OF THROMBOEMBOLISM IN THE NEUROSURGICAL PATIENT - A REVIEW NEUROSURGERY Powers, S. K., Edwards, M. S. 1982; 10 (4): 509-513

    Abstract

    The incidence of postoperative thromboembolic complications in neurosurgical patients is 29 to 43%. However, anticoagulant treatment of these complications increases the inherent risk of hemorrhage into the operative site. We have reviewed the literature on the prophylaxis of deep vein thrombosis and pulmonary embolism; the incidence of thromboembolic complications, the mechanism of deep venous thrombosis, risk factors, and methods of prophylaxis for deep vein thrombosis are discussed in relation to possible prophylactic treatment of neurosurgical patients. We conclude from our review that low dose heparin therapy is indicated for patients undergoing elective neurosurgical procedures, especially for patients over the age of 40 and for patients under the age of 40 who are known to be at risk of developing thromboembolic complications.

    View details for Web of Science ID A1982PA92600018

    View details for PubMedID 7099403

  • CSF POLYAMINES - A NEW AND IMPORTANT MEANS OF MONITORING PATIENTS WITH MEDULLOBLASTOMA CANCER MARTON, L. J., Edwards, M. S., Levin, V. A., LUBICH, W. P., Wilson, C. B. 1981; 47 (4): 757-760

    Abstract

    An earlier study that showed the importance of cerebrospinal fluid polyamine levels for monitoring patients harboring medulloblastomas was expanded to 210 determinations evaluated in 32 patients. The results and conclusions of our earlier study have been confirmed in this expanded patient group. Patient status, with regard to either progression or regression of tumor, was determined by correlating polyamine levels with neurologic examination, computerized tomography, radionuclide scan, cerebrospinal fluid cytology, and myelography. The polyamine assay was predictive of recurrence in 15 patients; three false negatives and no false positives were found. We feel that cerebrospinal fluid polyamine determinations should be a routine diagnostic procedure in the long-term monitoring of patients harboring medulloblastoma.

    View details for Web of Science ID A1981LB77800020

    View details for PubMedID 7226023

  • SONOGRAPHY OF THE ADULT BRAIN THROUGH SURGICAL DEFECTS AMERICAN JOURNAL OF NEURORADIOLOGY Gooding, G. A., Boggan, J. E., Bank, W. O., BEGLIN, B., Edwards, M. S. 1981; 2 (5): 449-452

    View details for Web of Science ID A1981ME56700011

    View details for PubMedID 6792883

  • CHEMOTHERAPY OF PEDIATRIC BRAIN-STEM TUMORS JOURNAL OF NEUROSURGERY Fulton, D. S., Wara, W. M., Edwards, M. S., Wilson, C. B., Levin, V. A. 1981; 54 (6): 721-725

    Abstract

    Forty-five children harboring brain-stem tumors were treated at the University of California, San Francisco, between 1969 and 1979. Pathological diagnoses were made in 19 patients. All patients received radiation therapy (RT). Thirteen patients received chemotherapy before, during, or immediately after RT. Twenty-four patients were treated with chemotherapy at the time of tumor progression, after initial treatment with RT alone. No statistically significant difference in time to tumor progression or survival was found for treatment with chemotherapy as an adjuvant to RT compared to treatment with RT alone followed by chemotherapy administered at the time of tumor progression. There were, however, more long-term survivors in the group that was first treated with chemotherapy at the time of tumor progression. There was no statistically significant correlation between survival and tumor pathology or location, although there were more long-term survivors among patients harboring low-grade gliomas and among patients with tumors confined to the midbrain. The authors documented the response of some brain-stem tumors to chemotherapy; however, cooperative controlled studies will be required to determine the optimum treatment for this disease.

    View details for Web of Science ID A1981LT03800001

    View details for PubMedID 6264050

  • INTRATHECAL CHEMOTHERAPY FOR LEPTOMENINGEAL DISSEMINATION OF MEDULLOBLASTOMA CHILDS BRAIN Edwards, M. S., Levin, V. A., SEAGER, M. L., Wilson, C. B. 1981; 8 (6): 444-451

    Abstract

    Cerebrospinal fluid dissemination of medulloblastoma occurs despite adequate systemic chemotherapy, and unless it is present at the time of initial diagnosis, occurs late in the course of the disease. Intrathecal chemotherapy with an implanted Ommaya reservoir can produce short-term benefit. We report here our protocol for and the results of intrathecal chemotherapy for leptomeningeal dissemination of medulloblastoma.

    View details for Web of Science ID A1981MS92400007

    View details for PubMedID 6796342

  • DELAYED SCIATIC PALSY AFTER TOTAL HIP-REPLACEMENT - CASE-REPORT NEUROSURGERY Edwards, M. S., Barbaro, N. M., ASHER, S. W., Murray, W. R. 1981; 9 (1): 61-63

    Abstract

    A 33-year-old woman with a 22-year history of juvenile rheumatoid arthritis developed right lower extremity sciatica 32 months after total hip arthroplasty. Physical examination and electromyography localized the abnormality to the sciatic nerve proximal to the midthigh level, involving the branch to the short head of the biceps femoris muscle. At surgical exploration, a sharp spur of methyl methacrylate, used to cement the acetabular prosthesis to the acetabulum, was found to have eroded through the lateral half of the sciatic nerve. The sciatica was relieved by neurolysis. The etiology of sciatic neuropathy after total hip replacement is reviewed.

    View details for Web of Science ID A1981MB19400010

    View details for PubMedID 7279174

  • DYNAMIC COMPUTED-TOMOGRAPHY OF THE BRAIN - TECHNIQUES, DATA-ANALYSIS, AND APPLICATIONS AMERICAN JOURNAL OF ROENTGENOLOGY Norman, D., Axel, L., BERNINGER, W. H., Edwards, M. S., Cann, C. E., REDINGTON, R. W., Cox, L. 1981; 136 (4): 759-770

    Abstract

    Rapid sequence computed tomography (CT) scanning has many potential applications in studying intracranial physiologic events. However, visual inspection of these rapid sequence scans fails to extract the large amount of information inherent in the digital data. The concept of corrected mean transit time applied to rapid sequence scans after intravenous bolus injection of contrast material provides quantitative data on relative hemispheric flow. Use of histogram-based areas of interest permits accurate and reproducible identification of anatomic structures including arteries and gray and white matter. Gamma variate curve fit techniques reduce statistical noise. The concept of transit time can be expanded to the creation of functional CT images.

    View details for Web of Science ID A1981LJ22400018

    View details for PubMedID 6784472

  • MODIFIED PROCARBAZINE, CCNU, AND VINCRISTINE (PCV-3) COMBINATION CHEMOTHERAPY IN THE TREATMENT OF MALIGNANT BRAIN-TUMORS CANCER TREATMENT REPORTS Levin, V. A., Edwards, M. S., Wright, D. C., SEAGER, M. L., SCHIMBERG, T. P., Townsend, J. J., Wilson, C. B. 1980; 64 (2-3): 237-241

    Abstract

    Fifty-eight patients harboring recurrent malignant brain tumors were evaluated. CCNU (110 mg/m2) was administered on Day 1, procarbazine (60 mg/m2) was administered daily for 14 days beginning on Day 8, and vincristine (1.4 mg/m2) was administered on Days 8 and 29 of each 6-week cycle of therapy. Therapy was continued until tumor progression was documented. Before each course, a neurologic examination was performed and radionuclide and computerized tomographic scans were obtained. Response and progression were defined as improvement or deterioration, respectively, in at least two of the three tests. Of the 46 patients harboring recurrent malignant gliomas, 12 (26%) responded to therapy, 18 (39%) had tumor progression, and 16 (35%) had disease stability. Nineteen of the 46 patients were not previously treated with another form of chemotherapy: eight (42%) responded to therapy, eight (42%) had disease stability, and only three (16%) had early tumor progression. The median time to tumor progression was 26 weeks for patients responding to therapy or having disease stability. Approximately 30% of the patients were alive without evidence of tumor progression at 1 year. Evaluated by time to tumor progression and rate of tumor response or stabilization, this combination was similar to the BCNU-5-fluorouracil combination used for patients harboring recurrent malignant glioma.

    View details for Web of Science ID A1980KH90000007

    View details for PubMedID 7407756

  • CHEMOTHERAPY OF PEDIATRIC POSTERIOR-FOSSA TUMORS CHILDS BRAIN Edwards, M. S., Levin, V. A., Wilson, C. B. 1980; 7 (5): 252-260

    Abstract

    Results of chemotherapy of recurrent posterior fossa tumors in children are presented. Cerebellar astrocytoma, ependymoma, and brain stem glioma have all shown objectively determined responses to treatment with nitrosourea compounds (BCNU or CCNU). Medulloblastoma has shown objectively determined response to various chemotherapeutic agents; but in our experience the best responses have been obtained with a combination of a nitrosourea (CCNU), vincristine, and procarbazine. Although chemotherapy after recurrence has significantly prolonged the life of the patients, cure has not been achieved. Theoretical considerations regarding the failure of initial therapy and the inadequacy of subsequent chemotherapy are discussed.

    View details for Web of Science ID A1980KZ98700003

    View details for PubMedID 7471913

  • NONOPERATIVE TREATMENT OF BRAIN ABSCESSES IN SELECTED HIGH-RISK PATIENTS JOURNAL OF NEUROSURGERY Rosenblum, M. L., Hoff, J. T., Norman, D., Edwards, M. S., Berg, B. O. 1980; 52 (2): 217-225

    View details for Web of Science ID A1980JC71500009

    View details for PubMedID 7351561

  • CEREBRAL CONVEXITY EPIDERMOID TUMOR SUBSEQUENT TO MULTIPLE PERCUTANEOUS SUBDURAL ASPIRATIONS - CASE-REPORT JOURNAL OF NEUROSURGERY Gutin, P. H., Boehm, J., Bank, W. O., Edwards, M. S., Rosegay, H. 1980; 52 (4): 574-577

    View details for Web of Science ID A1980JL93400019

    View details for PubMedID 7373381

  • REVERSAL OF CHRONIC OCULAR ISCHEMIA BY EXTRACRANIAL-INTRACRANIAL ARTERIAL BYPASS - CASE-REPORT NEUROSURGERY Edwards, M. S., CHATER, N. L., Stanley, J. A. 1980; 7 (5): 480-483

    View details for Web of Science ID A1980KT27800011

    View details for PubMedID 7442994

  • LANGUAGE OF NEURORRHAPHY JOURNAL OF NEUROSURGERY Rosegay, H., Edwards, M. S. 1980; 52 (1): 143-144

    View details for Web of Science ID A1980JA54900026

    View details for PubMedID 6985652

  • BRAIN-TUMOR CHEMOTHERAPY - AN EVALUATION OF AGENTS IN CURRENT USE FOR PHASE-II AND PHASE-III TRIALS CANCER TREATMENT REPORTS Edwards, M. S., Levin, V. A., Wilson, C. B. 1980; 64 (12): 1179-1205

    Abstract

    The reported English-language literature since 1969 on chemotherapy for malignant brain tumors has been collated, and reports of drugs or drug combinations used in phase II or III trials or with adjunctive therapies are reviewed. A significant fraction of the literature contained only anecdotal information, and even in the reports of more systematic trials, the criteria used to evaluate response were variable, ranging from subjective evaluation of clinical improvement to more stringent evaluations using one or more neurodiagnostic tests. A more consistent method of determining response is needed to facilitate comparison of different treatment protocols in the future, and guidelines for this are suggested. It appears that drugs of small molecular size (less than 450 daltons) and high lipid solubility have been the most effective. Single-agent chemotherapy using cell-cycle-specific drugs has, however, been disappointing. The nitrosoureas (especially BCNU) used either singly or in combination have consistently been the most effective agents in phase II and III trials. The combination of irradiation with adjunctive BCNU remains, for the present, the standard against which all other phase II and III protocols should be compared. New drugs for phase II evaluations are sorely needed. There is also need for new combination-drug and sequential-drug protocols for evaluation. The use of radiosensitizing agents with more novel radiation therapy fractionations and in combination with adjunctive drug therapies holds some promise for improving the disappointing results obtained thus far with chemotherapy for malignant brain tumors.

    View details for Web of Science ID A1980LL48800002

    View details for PubMedID 7008937

  • QUANTITATIVE OBSERVATIONS OF THE ACUTE EFFECTS OF X-IRRADIATION ON BRAIN CAPILLARY-PERMEABILITY .1. INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Levin, V. A., Edwards, M. S., Byrd, A. 1979; 5 (9): 1627-1631

    View details for Web of Science ID A1979HZ69600045

    View details for PubMedID 94058

  • QUANTITATIVE OBSERVATIONS OF THE SUB-ACUTE EFFECTS OF X-IRRADIATION ON BRAIN CAPILLARY-PERMEABILITY .2. INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Edwards, M. S., Levin, V. A., Byrd, A. 1979; 5 (9): 1633-1635

    View details for Web of Science ID A1979HZ69600046

    View details for PubMedID 536271

  • PREDICTIVE VALUE OF CEREBROSPINAL-FLUID POLYAMINES IN MEDULLOBLASTOMA CANCER RESEARCH MARTON, L. J., Edwards, M. S., Levin, V. A., LUBICH, W. P., Wilson, C. B. 1979; 39 (3): 993-997

    Abstract

    Seventy-five cerebrospinal fluid polyamine determinations were evaluated in 16 patients with medulloblastoma. Parameters utilized in evaluating patient status for correlation with the polyamine concentrations were neurological examination, computerized tomography, radionuclide scan, myelography, and cerebrospinal fluid cytology. Fifteen of the 16 patients showed absolute correlation with the eventual clinical picture. One determination on one patient resulted in a false negative. No false positives have been observed to date.

    View details for Web of Science ID A1979GL34100049

    View details for PubMedID 427786

  • PHASE-II EVALUATION OF THIOTEPA FOR TREATMENT OF CENTRAL NERVOUS-SYSTEM TUMORS CANCER TREATMENT REPORTS Edwards, M. S., Levin, V. A., SEAGER, M. L., PISCHER, T. L., Wilson, C. B. 1979; 63 (8): 1419-1421

    Abstract

    Nineteen patients with primary malignant gliomas were treated with thioTEPA. It was found to be ineffective in 13 evaluable patients.

    View details for Web of Science ID A1979HP23200036

    View details for PubMedID 225030

  • CHEMOTHERAPY OF RECURRENT MEDULLOBLASTOMA WITH COMBINED PROCARBAZINE, CCNU, AND VINCRISTINE JOURNAL OF NEUROSURGERY CRAFTS, D. C., Levin, V. A., Edwards, M. S., PISCHER, T. L., Wilson, C. B. 1978; 49 (4): 589-592

    Abstract

    Seventeen patients with recurrent medulloblastoma were treated with a combination of three drugs: procarbazine, CCNU, and vincristine (PCV). Tumor recurrence was documented at varying periods following surgery and radiotherapy. Among 16 evaluable patients, ten showed a response to PCV on the basis of subjective neurological improvement and a decrease in tumor size by radiological criteria. Five patients were designated as having stable disease on the basis of no change in neurological status and tumor size. One patient showed uninterrupted progression of disease. The median time to progression for all patients was 45 weeks. Significnat myelotoxicity, exacerbated by prior spinal irradiation, compromised therapy. After an initial response, it was often necessary to reduce the higher doses of CCNU and procarbazine that caused concomitant bone-marrow toxicity; as a consequence of the lowered doses, tumor progression was then frequently observed. The authors conclude that PCV is an effective form of palliative therapy for recurrent medulloblastoma.

    View details for Web of Science ID A1978FQ19100014

    View details for PubMedID 690688

  • CAVERNOUS SINUS SYNDROME PRODUCED BY COMMUNICATION BETWEEN EXTERNAL CAROTID-ARTERY AND CAVERNOUS SINUS JOURNAL OF NEUROSURGERY Edwards, M. S., Connolly, E. S. 1977; 46 (1): 92-96

    Abstract

    The authors present two cases of cavernous sinus syndrome with spontaneous onset secondary to arteriovenous malformations and review the cases reported previously. These malformations enlarge slowly and produce symptoms only in adult life. Diagnosis may be difficult when there is no associated bruit. Adequate evaluation necessitates selective angiography of both the internal and external carotid artery circulation and the vertebral circulation. Conservative treatment is recommended unless symptoms worsen or there is progressive loss of vision.

    View details for Web of Science ID A1977CR17600012

    View details for PubMedID 830819

Conference Proceedings


  • P16 deletion and mutation analysis in human brain tumors Barker, F. G., Chen, P. C., Furman, F., Aldape, K. D., Edwards, M. S., Israel, M. A. SPRINGER. 1997: 17-23

    Abstract

    We screened human primary and recurrent malignant glioma, juvenile pilocytic astrocytoma, medulloblastoma, and meningioma tissue specimens for alterations in p16 gene structure. Single strand conformation polymorphism (SSCP) analysis was used to screen for point mutations, and a quantitative polymerase chain reaction-based assay was used to screen for homozygous gene deletions. In malignant glioma specimens, homozygous p16 gene deletions were significantly more common in high-grade tumors than in low-grade gliomas. Point mutations causing alteration in predicted protein structure were not detected. Medulloblastomas showed rare homozygous deletions and no point mutations. No mutations were detected in meningiomas.

    View details for Web of Science ID A1997WJ07400004

    View details for PubMedID 9049826

  • PATTERN OF RECURRENCE OF MEDULLOBLASTOMA AFTER LOW-DOSE CRANIOSPINAL RADIOTHERAPY Wara, W. M., LE, Q. T., Sneed, P. K., Larson, D. A., Prados, M. D., Levin, V. A., Edwards, M. S., Weil, M. D. PERGAMON-ELSEVIER SCIENCE LTD. 1994: 551-556

    Abstract

    We retrospectively evaluated relapse of medulloblastoma after low- or high-dose craniospinal radiotherapy, and after conventional or hyperfractionated posterior fossa irradiation.Ninety-two pediatric patients were treated postoperatively since 1970 at the University of California, San Francisco. Until 1989, we employed conventional fractionation with low (< or = 30 Gy) or high-dose craniospinal fields and low-dose (< or = 56 Gy) posterior fossa boosts. Recently, hyperfractionation delivered low- or high-dose to the craniospinal axis and high-dose to the posterior fossa. Most patients treated after 1979 received chemotherapy.Median follow-up was 70 months. Five-year disease-free survival was 36% (22% for poor-risk vs. 59% for good-risk patients). Five-year overall survival was 52% (43% for poor vs. 68% for good-risk). Neither the dose to the posterior fossa nor the craniospinal axis was statistically related to recurrence. Failure in the posterior fossa occurred despite boosts greater than 56 Gy. Females, over the age of 6 years, had significantly better relapse-free survival than males of the same age. Six of the 54 patients who relapsed were long-term survivors.Low-dose craniospinal radiotherapy, where the majority of patients received chemotherapy, was not associated with increased failure. High-dose posterior fossa hyperfractionation did not improve control. Long-term survival was noted in a number of patients after relapse. We recommend 60 Gy or greater with conventional fractions to the primary area, and continued study of low-dose craniospinal irradiation with adjuvant chemotherapy.

    View details for Web of Science ID A1994PK60400004

    View details for PubMedID 7928485

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