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PURPOSE NRG Oncology/RTOG 9802 (ClinicalTrials.gov Identifier: NCT00003375 ) is a practice-changing study for patients with WHO low-grade glioma (LGG, grade II), as it was the first to demonstrate a survival benefit of adjuvant chemoradiotherapy over radiotherapy. This post hoc study sought to determine the prognostic and predictive impact of the WHO-defined molecular subgroups and corresponding molecular alterations within NRG Oncology/RTOG 9802. METHODS IDH1/2 mutations were determined by immunohistochemistry and/or deep sequencing. A custom Ion AmpliSeq panel was used for mutation analysis. 1p/19q codeletion and MGMT promoter methylation were determined by copy-number arrays and/or Illumina 450K array, respectively. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Hazard ratios (HRs) were calculated using the Cox proportional hazard model and tested using the log-rank test. Multivariable analyses (MVAs) were performed incorporating treatment and common prognostic factors as covariates. RESULTS Of the eligible patients successfully profiled for the WHO-defined molecular groups (n = 106/251), 26 (24%) were IDH-wild type, 43 (41%) were IDH-mutant/non-codeleted, and 37(35%) were IDH-mutant/codeleted. MVAs demonstrated that WHO subgroup was a significant predictor of PFS after adjustment for clinical variables and treatment. Notably, treatment with postradiation chemotherapy (PCV; procarbazine, lomustine (CCNU), and vincristine) was associated with longer PFS (HR, 0.32; P = .003; HR, 0.13; P < .001) and OS (HR, 0.38; P = .013; HR, 0.21; P = .029) in the IDH-mutant/non-codeleted and IDH-mutant/codeleted subgroups, respectively. In contrast, no significant difference in either PFS or OS was observed with the addition of PCV in the IDH-wild-type subgroup. CONCLUSION This study is the first to report the predictive value of the WHO-defined diagnostic classification in a set of uniformly treated patients with LGG in a clinical trial. Importantly, this post hoc analysis supports the notion that patients with IDH-mutant high-risk LGG regardless of codeletion status receive benefit from the addition of PCV.

BackgroundGrade 2 gliomas occur most commonly in young adults and cause progressive neurologic deterioration and premature death. Early results of this trial showed that treatment with procarbazine, lomustine (also called CCNU), and vincristine after radiation therapy at the time of initial diagnosis resulted in longer progression-free survival, but not overall survival, than radiation therapy alone. We now report the long-term results. MethodsWe included patients with grade 2 astrocytoma, oligoastrocytoma, or oligodendroglioma who were younger than 40 years of age and had undergone subtotal resection or biopsy or who were 40 years of age or older and had undergone biopsy or resection of any of the tumor. Patients were stratified according to age, histologic findings, Karnofsky performance-status score, and presence or absence of contrast enhancement on preoperative images. Patients were randomly assigned to radiation therapy alone or to radiation therapy followed by six cycles of combination chemotherapy...

Study Design This is a retrospective review of a prospectively maintained database of anterior cervical discectomy and fusion with plating (ACDFP) cases. Objective The aim of this study is to evaluate within a clinical practice evidence-based results of short-term morbidity with multilevel ACDFP. Methods Clinical morbidity, length of hospital stay, visual analog scale (VAS) and Odom scores, Neck Disability Index (NDI), hardware failure, and return-to-work (RTW) status were prospectively collected in an electronic database for 678 patients who underwent 1-, 2-, 3-, or 4-level ACDFP during an 8-year period. A total of 519 patients met the study criteria and were retrospectively analyzed. Results The majority of all patients noted “Excellent” or “Good” status for 1 month (91%), 2 months (92%), and 3 months (96%). Patients with 1-, 2-, and 3-level ACDFP returned to work sooner, 60% at 1 month, 70% at 2 months, and 68% at 3 months. For 4-level patients, the majority did not RTW until 3 months (71%). The only significant increase in morbidity with increasing levels was hospital stay for 3- and 4-level ACDFP and RTW for 4-level ACDFP. Conclusion Multilevel ACDFP can be performed with low initial morbidity. An individual practice can review results to allow for ongoing evidence-based care. Final class of evidence - treatment Yes Study design RCT Cohort • Case control Case series Methods Concealed allocation (RCT) Intention to treat (RCT) Blinded/independent evaluation of primary outcome • F/U ≥ 85% Adequate sample size • Control for confounding Overall class of evidence III

This multicenter clinical study was performed to assess the safety and effectiveness of Trinity Evolution® (TE), a viable cellular bone allograft, in combination with a PEEK interbody spacer and supplemental anterior fixation in patients undergoing anterior cervical discectomy and fusion (ACDF). In a prospective, multi-center study, 31 patients that presented with symptomatic cervical degeneration at one vertebral level underwent ACDF with a PEEK interbody spacer (Orthofix, Inc., Lewisville, TX, USA) and supplemental anterior fixation. In addition all patients had the bone graft substitute, Trinity Evolution (Musculoskeletal Transplant Foundation, Edison, NJ, USA), placed within the interbody spacer. At 6 and 12 months, radiographic fusion was evaluated as determined by independent radiographic review of angular motion (≤4°) from flexion/extension X-rays combined with presence of bridging bone across the adjacent endplates on thin cut CT scans. In addition other metrics were measured including function as assessed by the Neck Disability Index (NDI), and neck and arm pain as assessed by individual Visual Analog Scales (VAS). The fusion rate for patients using a PEEK interbody spacer in combination with TE was 78.6 % at 6 months and 93.5 % at 12 months. When considering high risk factors, 6-month fusion rates for patients that were current or former smokers, diabetic, overweight or obese/extremely obese were 70 % (7/10), 100 % (1/1), 70 % (7/10), and 82 % (9/11), respectively. At 12 months, the fusion rates were 100 % (12/12), 100 % (2/2), 100 % (11/11) and 85 % (11/13), respectively. Neck function, and neck/arm pain were found to significantly improve at both time points. No serious allograft related adverse events occurred and none of the 31 patients had subsequent additional cervical surgeries. Patients undergoing single-level ACDF with TE in combination with a PEEK interbody spacer and supplemental anterior fixation had a high rate of fusion success without serious allograft-related adverse events.

Objective To determine the facial nerve outcomes at a tertiary neurotological referral center specializing in acoustic neuroma and skull base surgery. Study Design Retrospective review of 100 consecutive patients in whom acoustic neuromas were removed using all of the standard surgical approaches. Methods Functional facial nerve outcomes were independently assessed using the House-Brackmann facial nerve grading system. Results The tumors were categorized as small, medium, large, and giant. If one excludes the three patients with preoperative facial palsies, 100% of the small tumors, 98.6% of the medium tumors, 100% of the large tumors, and 71% of the giant tumors had facial nerve function grade I-II/VI after surgery. Conclusion Facial nerve results from alternative nonsurgical treatments must be compared with facial nerve outcomes from experienced surgical centers. Based on the facial nerve outcomes from our 100 consecutive patients, microsurgical resection remains the preferred treatment modality for acoustic tumors.

During a 3-year period, 25 caudalis dorsal root entry zone (DREZ) operations were done for severe, facial pain. Intraoperative brainstem recordings were done before and after DREZ in all patients. Primary diagnosis included refractory trigeminal neuralgia, atypical headaches or facial pain, posttraumatic closed head injuries, postsurgical anesthesia dolorosa, multiple sclerosis, brainstem infarction, postherpetic neuralgia and cancer-related pain. At the time of discharge, good to excellent pain relief was present in 24/25 patients and fair relief in 1. At 1 month, 19/25 (76%) patients had good to excellent results and at 3 months following surgery, 17/25 (68%) continued to have good to excellent pain relief. One year following surgery, 18 patients could be evaluated, 12/18 (67%) still considered their relief as good to excellent, 2 fair and 4 poor. Transient postoperative ataxia was present in 15/25 patients (60%), but was largely resolved at 1 months. In 3/18 (17%) patients, a degree of ataxia was still present at 1 year although in none was it disabling. Two patients had transient diplopia, and 3 had increased corneal anesthesia with 1 later developing a keratitis. No surgical or postsurgical mortality was noted. This procedure has proven to be a satisfactory treatment for many patients with debilitating facial pain syndromes with acceptable morbidity.

Stereotactic neurosurgery is the arena in which the past meets the present on many levels. Preserved skulls from South America, Africa, and Europe testify to man's early attempts at cranial surgery. Stereotactic approaches and systems, as well as the new innovative interactive image-guided devices, are efforts to explore and treat the afflictions of the human brain in both its literal and figurative aspects.

BACKGROUND: Recent results of R9802 (Buckner et al; J Clin Oncol 32:5s, 2014 (suppl; abstr 2000)) demonstrated that PCV given with RT at the time of initial diagnosis prolongs both progression-free survival (PFS) and overall survival (OS) for all patients enrolled in the trial. Herein, we report the impact of treatment on PFS and OS based upon specific histologic type. METHODS: Eligibility criteria included age 40 with any extent of resection, and supratentorial grade ll oligodendroglioma (O), oligo-astrocytoma (OA), or astrocytoma (A). Patients were stratified by age, histology, Karnofsky Performance Status, and presence versus absence of contrast enhancement on the preoperative imaging study and randomized to RT alone (54 Gy in 30 fractions) or RT followed by 6 cycles of PCV chemotherapy. In an exploratory analysis, we used the log rank test to compare survival and progression free survival (PFS) distributions for each histologic type. RESULTS: 251 eligible patients were accrued from 1998 to 2002: 107 had O, 79 had OA, and 65 had A. In total, 67% have progressed and 55% have died. Median PFS (RT vs. RT + PCV) overall, O, OA, and A, respectively, are 4.0 vs 10.4 (p < 0.001); 6.0 vs not reached (NR) (p < 0.001); 3.0 vs 8.9 (p = 0.01); and 1.8 vs 3.7 (p = 0.06) years. Median survival times (RT vs. RT + PCV) overall, O, OA, and A, respectively, are 7.8 vs 13.3 (p = 0.002); 10.8 vs NR (p = 0.008); 5.9 vs 11.4 (p = 0.05); and 4.4 vs 7.7 (p = 0.31) years. CONCLUSIONS: For grade 2 glioma patients with less than gross total tumor resection or >40 years of age, PCV + RT prolongs both OS and PFS compared with RT alone. The observed benefit is most definitive for O and OA patients.

2000 Background: Early results of R9802 (Shaw et al: J Clin Oncol. 2012; 30(25):3065-70) demonstrated that PCV given with RT at the time of initial diagnosis prolongs progression-free survival (PFS...

Publisher Summary This chapter examines the preliminary report on adrenal medullary grafting from the American Association of Neurological Surgeons Graft Project. This data is preliminary and subject to alteration as further data is accumulated and analyzed. It is not part of a controlled study but is the collection of clinical experience of the participants. Therefore, the data has been cautiously analyzed relative to the experience being described. The data is discussed in the chapter in various subgroups and not as a single unit or net result. It would be inappropriate to describe an overall complication rate, because the patient selection criteria, surgical procedure, and evaluation criteria vary with each center. In the chapter, rather than discussing an overall complication rate, complication rates are discussed for various types of patient characteristics and surgical procedures. The data are meant to provide a framework to evaluate the current state of the art of transplantation and provide insight into the direction for future studies.

A case of a brain stem abscess that was successfully treated using CT guided stereotaxy together with antibiotic therapy is presented. The literature is reviewed and the role of stereotaxy in the treatment of brain stem abscess is discussed.

✓ Current diagnostic and therapeutic modalities for malignant human gliomas are largely nonspecific. The development of monoclonal antibodies (MA's) with their high degree of specificity may allow precise tumor imaging and selective administration of therapeutic agents. However, the ability of these antibodies to specifically localize tumor tissue in vivo remains speculative. This study compares the localization and imaging properties of two MA's: a specific human glioma-associated extracellular matrix glycoprotein MA, 81C6, and a nonspecific control MA, 45.6, against a human glioma cell line, D-54 MG, intracranially inoculated into athymic rats. Forty-one animals received MA's labeled with iodine-131 (131I) or 125I and underwent imaging with a gamma camera. The images were independently evaluated and compared to tissue radioactivity levels. Radiolabeled antiglioma MA 81C6 specifically localized in intracranial xenografts. The percent of injected dose per gram of tissue for tumor was 1.707 ± 0.405/gm for 81C6 and 0.118 ± 0.056/gm for 45.6. All other organs had equivalent levels of specific and nonspecific MA's. For brain, these were 0.004 ± 0.002/gm and 0.005 ± 0.005/gm, respectively, and for the other organs, the range was from 0.053 to 0.284/gm. Statistically, 45.6 achieved levels in tumor that were significantly higher than normal brain (p < 0.05) but significantly less than that achieved with 81C6 (p < 0.005). With 81C6, the degree of localization was high enough to allow imaging of intracranial tumors at sizes as small as 20 mg. Intracranial tumors were imaged with 45.6 only when they achieved sizes greater than 300 mg. In this imaging study, radiolabeled 81C6, a specific antiglioma MA, proved to be significantly better for imaging small and intermediate-sized tumors than the control MA's. Large tumors were visualized by both MA's, although higher quality scans were obtained earlier and more frequently with specific MA's than with nonspecific immunoglobulin G. These data suggest that specific MA's have a role to play in both the diagnosis and treatment of primary intracranial human tumors.

Supratentorial glioblastoma multiforme (GBM) is a lethal malignancy. Subtotal surgical resection and post operative external beam radiotherapy palliate symptoms and prolong survival, but very few patients survive more than 3 years following diagnosis.‘,3,20*32,43,46,48*5’*58,66 Whereas the probability of survival of supratentorial anaplastic astrocytoma (AA) is slightly better, most patients will still succumb to the tumor.58-60*66 The resistance of these neoplasms to conventional therapies has prompted many physicians to undertake new clinical and laboratory investigations. These have included the use of chemotherapy,44 immunotherapy,40 multiple-fraction-perday radiotherapy,2’,34,49 radiotherapy with chemical radiosensitizers,6’ and neutron radiotherapy.45 As interest in the biology and treatment of malignant gliomas has increased, many conceptual verities have been proposed to guide therapeutic investigations, These include the significance of the cellular heterogeneity of AA and GBM,‘2,24 the presence of the blood-brain-barrier (BBB) as a functional obstruction to chemotherapy, and the local nature of these tumors. In this editorial, we focus on the last of these premises. We have selected this issue because of its major implications for any treatment that is directed at a specific portion of the brain rather than the whole brain: BBB disruption, intracarotid drug administration, and brain brachytherapy. Interstitial brachytherapy is used for primary and recurrent GBM and AA. The technique consists of the stereotactic computed tomography (CT) or magnetic resonance imaging (MRI) guided placement of coaxial catheters within and around the tumor. Radioactive sources are after-loaded into the catheters to deliver continuous low-dose rate irradiation. After a specified dose is delivered, the system is removed.22~27~28~39~45 Interstitial hyperthermia generated by implanted microwave antennae may be administered in conjunction with the radiation.52 One of the justifications invoked for brachytherapy is the concept of malignant gliomas as localizedlesions. Allusions to this concept abound in the literature. “Most malignant gliomas are localized to a single area of the brain, central nervous system (CNS) metastases from these tumors are uncommon and systemic metastases are rare.“29 “Since an astrocytoma is almost invariably a nonmetastatizing single mass, ideally it should lend itself best to regional treatment.“** “Because a primary brain tumor is most often a localized disease, hyperthermia, intratumoral chemotherapy, and interstitial irradiation, the stereotactic placement of radioactive sources directly into brain tumors, have been suggested as possible local treatments for brain tumors.“*’

✓ Different methods were evaluated for delivering iodine-125 monoclonal antibodies (Mab's) to the central nervous system in 40- to 99-gm Fischer rats. By evaluating interhemispheric, interregional, and brain:blood ratios of Mab's, the efficacy of intracarotid (IC) or intravenous (IV) administration of Mab's with and without prior IC perfusion with 0.9% NaCl (normal saline, NS), 1.4 M mannitol, or 1.6 M arabinose, or of femoral artery perfusion with 1.4 M mannitol was evaluated. No difference was seen between IC and IV administration of Mab's with or without prior perfusion. Intracarotid perfusion with hyperosmolar agents was required to disrupt the blood-brain barrier (BBB) and to significantly elevate brain levels of Mab's. The brain and blood levels of Mab's were elevated in all regions of the brain following hyperosmolar BBB disruption. However, the levels were significantly higher in the ipsilateral hemisphere, with cross-over occurring primarily in the vascular distribution of the contralateral anterior cerebral artery. Intracarotid hyperosmolar perfusion produced 450% to 500% increases in ipsilateral and 240% to 280% increases in contralateral hemispheric brain:blood Mab ratio levels compared to those achieved with NS perfusion. For IC perfusion of mannitol or arabinose, flow rates ranging from 0.017 to 0.052 ml/sec were equally effective in disrupting the BBB. Insignificant morbidity and mortality rates were noted up to 2 weeks following BBB disruption. Additional ligation of major extracranial branches of the external and internal carotid arteries prior to IC perfusion did not result in a selective increase in hemispheric Mab levels. Temporally, following hyperosmolar BBB disruption, brain:blood Mab ratios remained elevated bilaterally at 7 days after Mab delivery, with the ipsilateral hemispheric levels remaining significantly elevated compared with the contralateral hemispheric levels until Day 5, when the ratio returned to the nonperfused range. Catheterization was required in the small animals and was performed under magnification in 10 to 20 minutes, with less than an 8% overall morbidity and mortality. The methodology developed should prove helpful in delivery of Mab's or other agents in rat tumor models and experimental models for other disease entities.

Surgical biopsies from 2 human craniopharyngiomas were transplanted subcutaneously into 6 athymic "nude" mice. Morphologically characteristic craniopharyngiomas grew in 5 of these animals. In 4 animals growth was sufficient to allow transplantation into a second generation of animals. In all, 11 craniopharyngiomas were present at autopsy in the 14 animals into which the tumors had been transplanted. The tumors that grew in the animals had the same adamantinomatous architecture, epithelial nests, and keratinized nodules that were present in the original surgical sample and that are characteristic of human craniopharyngiomas. It may be possible to study growth characteristics and therapeutic sensitivities of human craniopharygniomas growing in "nude" mice.

Since 1924, when ependymomas were first classified as a distinctive glial neoplasm by Bailey, much has been published concerning these tumors, but there are important points of interest that are still not clear. In order to study more fully the clinical and pathologic characteristics of the ependymoma, we identified 62 patients with histologically proven neoplasms. Twenty-two were supratentorial, 21 were infratentorial, and 19 were intramedullary spinal cord tumors. These groups had mean ages of 17, 7, and 41 years, respectively, at the time of first symptoms. The presenting and accompanying symptoms were related to location and included headaches, nausea, visual changes, hemiparesis, and neck, back, and radicular pain. Neurological signs included papilledema, nystagmus, gait disturbance, cranial nerve palsies, altered mental status, paraparesis, and sensory dysfunction. Radiologic modalities of particular importance included computed tomography and myelography. Surgery and radiation therapy were the primary treatment modalities with median survival times from first symptoms being 92, 36, and 117 months for the above groups, respectively. Based on computer-generated survival curves, several characteristics significantly affected survival. These included tumor site, age, and neuraxis metastases. In patients with supratentorial tumors, cranial nerve palsies, microcystic changes, and mitotic figures were important, while in patients with infratentorial tumors, widened sutures, increased head circumference, age, epithelial features, and subependymal features significantly affected survival. Patients who had complete gross resection of a spinal cord tumor had no recurrences or mortality.

Intracranial hypertension and hydrocephalus with their attendant disturbances of hypothalamic function may produce autonomic disturbances as well as alterations in regulation of body temperature. Such alterations of thermal regulation have been recognized as an early sign of ventricular enlargement. However, an acute hyperthermic syndrome with autonomic disturbance as a consequence of hydrocephalus had not been described prior to the current report. Two male subjects with chronic ventriculoperitoneal shunts presented with just such a syndrome associated with each of several episodes of acute shunt failure and hydrocephalus. In each, hyperthermia was associated with changes in their level of consciousness, increased skeletal muscular tone, absence of pupillary light reflexes, and autonomic instability. With correction of the hydrocephalus, the autonomic disturbances and fever immediately cleared and the patients returned to their baseline state, only to have recurrent episodes with several repeated hydrocephalic events associated with shunt failures. Observations from human and experimental studies suggest some potential mechanisms for the development of the syndrome in these subjects. One of the subjects of the report was being treated with neuroleptics at the time of hospitalization. In him, and potentially in other similar patients, the syndrome could easily be confused with the neuroleptic malignant syndrome. The need for prompt appreciation of the correct diagnosis is emphasized in these subjects by the rapid clearing of the neurological signs after correction of the shunt malfunctions in both patients. (Arch Neurol 45:1037–1040, 1988)

The indications for stereotaxic biopsy in the management of patients with intracanial lesions is discussed. An overview of the different techniques available, and the author's technique and results are outlined.

The localisation of the radioiodinated Fab fragment of monoclonal antibody (Mab) 81C6, reactive with a glioma-associated extracellular matrix antigen, was studied in athymic mice bearing subcutaneous and intracranial xenografts of D-54 MG glioma cells. In vitro 81C6 Fab showed a marked loss of immunoreactivity and affinity for antigen compared to intact Mab 81C6. In vivo, the plasma half-life of 81C6 Fab was 7.0 hours compared to 2.1 days for 81C6. 81C6 Fab levels in tumours peaked at 2.6-3.8% injected dose/g in 2-6 h; Mab 81C6 reached 33.9% dose/g at 48 h. Localisation indices and tumour:tissue ratios were superior for Mab 81C6. Estimated radiation doses to tumour and normal tissues were lower for 131I-81C6 Fab than 131I-81C6. To realise the theoretical benefits of fragments as localising agents, Fab fragments of higher immunoreactivity and affinity, or bivalent F(ab')2 fragments are required.

At the present time, specific imaging and treatment of central nervous system malignancies is not possible. The development of monoclonal hybridoma technology may provide the solution to this problem. We have utilized human glioma-derived cell lines (HGCL) transplanted subcutaneously and intracranially into athymic mice and rats to evaluate the imaging and localizing properties of a panel of MAbs. MAbs 81C6, C12, and D12 and 81C6 Fab have shown significant in vivo localization against HGCL D-54 MG and 81C6 against U-251 MG when compared to equivalent non-specific MAbs. In subcutaneous D-54 MG-induced xenografts, maximal localization indices (LI) of up to 15.0 for 81C6, 6.8 for 81C6 Fab, 6.48 for C12, and 4.47 for D12 have been seen. The tumor-tissue ratios for normal brain have ranged from 235 for 81C6 to 167 for D12. The total percent injected dose for 81C6 was nearly 5% in U-251 MG tumors and 10% of the initial dose in D-54 tumors, while the percent injected dose for control MAb were 1.9% and 2.8%, respectively. Four subcutaneously growing U-251 MG tumors were clearly imaged using 1311-81C6. With intracranial growing D-54 MG,1311-81C6 provided external imaging of intracranial tumors at sizes as small as 20 mg while 131l-45.6, a non-specific MAb, provided imaging only when tumors achieved sizes greater than 300 mg. These data indicate that operationally specific MAbs and MAb Fab can specifically localize and be used to image human tumors transplanted into immunocompromised animals. The animal models described in this paper provide a sensitive method of evaluating MAbs in pre-human trials.

44 patients underwent intraoperative stimulation with a monopolar electrode prior to computed tomography (CT)-guided stereotactic biopsy. Stimulation at 2–100 Hz resulted in functional responses in 6/21 patients with subcortical or callosal lesions, 4/6 with basal ganglion lesions, 8/10 with thalamic and 4/4 with brainstem lesions. In all but 2 patients with mesencephalic lesions, where limited biopsy sites were available, an alternative biopsy site was used if a functional response was obtained. No morbidity was seen among these patients, although postbiopsy CT scans demonstrated small 3- to 7-mm hematomas in 5/11 patients. Retrospective review of 79 patients who underwent biopsies without stimulation demonstrated hematomas in 6/10 patients and a 3.3% transient surgical morbidity. These data indicate that postbiopsy hematomas are a relatively common occurrence, that intraoperative electrical stimulation within abnormal lesions can identify functional potential, and that avoidance of biopsies within these functional areas may be associated with reduced morbidity.

Despite extensive clinical use of brain tumor chemotherapy via the internal carotid artery (ICA), demonstration of efficacy and toxicity screening of ICA chemotherapy in brain tumor models has been limited. A method for performing ICA injections in 40- to 99-g Fischer rats is described, with documentation of its effect upon cerebral blood flow. A 33 gauge cannula was secured into a PE-10 catheter and, after ligation of the external carotid (ECA) and the pterygopalatine arteries, injections were made into the common carotid artery (CCA). The reliability of this method compared to CCA injection with and without ligation of the ECA was evaluated utilizing 15-micrometers 103Ru microspheres. With this technique, 68.3 +/- 11.19% of the microspheres lodged in the brain, compared to 28.9 +/- 21.3% to 32.7 +/- 19.8% for the other techniques (P less than 0.01). With this technique, regional perfusion of brain tumors can be done in the avian sarcoma virus rat glioma model, the D-54 MG human glioma-immunosuppressed rat transplantation model, and any of the large rat brain tumor models. The relevance of this method of experimental regional perfusion for the preclinical assessment of the efficacy and of the toxicity of chemotherapy and immunotherapy via the ICA is discussed.

Nonabsorbable silk sutures have been a frequently used foreign material in neurosurgery. In general, they are reliable and safe with minimal bio-incompatibility. Three pediatric neurosurgical patients came to clinical attention, however, because of delayed foreign-body reactions to silk sutures. The delayed atypical presentation of these patients delayed appropriate diagnosis and therapy. In two patients, the reaction presented as a delayed inflammation 7 years following surgical suture placement. In the other patient, the reaction caused delayed recurrent shunt failures and surgical wound breakdown. These three cases are used to introduce a discussion of the delayed response of the host to foreign material and its pertinence to neurosurgery.

In this study, the relationships among computed tomography (CT) characteristics, intraoperative impedance monitoring, and histologic features were evaluated in 46 patients. Preoperatively, the CT characteristics of the proposed trajectory of the biopsy needle were determined and correlated intraoperatively with the impedance profile as obtained with a monopolar electrode. An excellent correlation between high-resolution CT density characteristics and impedance patterns was seen (r = 0.897). A correlation was also seen between CT patterns/impedance profiles and histologic features. Impedance values were also useful in predicting variation between predicted and actual needle trajectory, determining the proximity of normal structures to the probe tip and detecting loculations within cystic structures.

✓ A 24-year-old man presented with a history of recurrent meningitis secondary to cerebrospinal fluid (CSF) rhinorrhea. The patient had bilateral optic disc dysplasia in association with a basal encephalocele, but had no midline facial anomalies. The syndrome is rare, and this is the first report of a patient with this disorder in the absence of facial or radiographic anomalies. The case serves to emphasize the importance of funduscopic examination in patients with spontaneous CSF rhinorrhea or recurrent meningitis, and stresses the value of Dextrostix examination of nasal secretions in the evaluation of suspected CSF rhinorrhea.

Limbic encephalitis (encephalopathy) is a rare paraneoplastic syndrome which rarely responds to antineoplastic therapy. The authors report the first case of limbic encephalopathy associated with testicular carcinoma and the first histologically confirmed encephalopathy which responded to antineoplastic therapy of the associated neoplasm. The clinical and pathologic characteristics of paraneoplastic encephalopathies are discussed along with the potential for reversal of the neurologic process with effective antitumor therapy.

Fifteen permanent cell lines derived from human gliomas were subcutaneously transplanted into athymic nude mice (nu/nu genotype, NIH Swiss and BALB/c backgrounds). Four were tumorigenic. Three of the four (D-54 MG, U-118 MG, and U-251 MG) produced progressively growing, solid, noncystic tumors. Subcutaneous volume measurement of these tumors, which correlated directly with tumor weight, was a reliable method for monitoring growth. All three cell lines which produced progressively growing subcutaneous tumors were also tumorigenic when cells were inoculated intracerebrally. These grew as well-circumscribed, intraparenchymal brain tumors. After initial implantation, each of the progressively growing, solid, subcutaneous tumors was histologically similar to the permanent cell lines from which it was derived. Tumors could be reliably passed, and stabilization of latency periods and growth rates developed. Tumors became morphologically less distinct in later passages, though some individual features remained. Mice bearing subcutaneous tumors from each of these cell lines were treated with a single ip dose of 25 mg/kg BCNU and compared to controls receiving only drug vehicle. A significant, but different, amount of reduction in tumor mass occurred among each of the three tumor lines. This model allows cell lines derived from human gliomas to be grown in animal hosts, thereby providing a potential means for evaluating growth parameters and chemotherapeutic responsiveness of tumors derived from individual human gliomas or cell lines.

Ollier's disease or multiple enchondromatosis is a deforming dysplastic disease of cartilage involving primarily the metaphyses and diaphyses of long bones. It is only rarely associated with sarcomatous degeneration of the enchondromas or other generalized neoplasms. A related disease, Maffucci's syndrome, is, however, associated with generalized tumors. We present the case of a 29-year-old, albino, black man with Ollier's disease who, as a child, underwent a number of orthopedic procedures for multiple limb deformities and fractures. At age 25, he developed hydrocephalus, progressive cranial nerve palsies, and a large enchondroma of the skull base. He subsequently underwent multiple shunt procedures and two suboccipital craniectomies. Eighteen months later, a brain computed tomographic (CT) scan revealed an intracerebellar mass, which was found to be an anaplastic astrocytoma. Two years later, he developed a right hemiparesis and sensory dysfunction with a diffuse supratentorial mass on CT scan. A stereotactic biopsy showed this to be a similar anaplastic astrocytoma. The literature concerning Ollier's disease is reviewed, and the intracerebral lesions associated with both Ollier's disease and Maffucci's syndrome are examined.

Fifteen permanent cell lines derived from human gliomas which are individually distinct by immunologic and biochemical criteria were evaluated to determine if morphologic or cell biologic parameters distinguished the 4 lines which were tumorigenic in athymic nude mice. By subjective morphologic appraisal, the 4 tumorigenic lines were considered "malignant" or "borderline," but 4 of the non-tumorigenic lines were also classified in this way. By objective criteria, these 15 lines varied markedly in percentage of piled-up cells, chromatin pattern, pleomorphism, nuclear to cytoplasmic ratio, number of bizarre multinucleate giant cells, presence of abnormal mitotic figures, percentage of colony formation in soft agar, saturation density, population doubling time, and absolute plating efficiency. Among these criteria, percentage of colony formation in soft agar had the highest correlation coefficiency with tumorigenicity, and when this parameter was held constant the only additional characteristic which correlated significantly (p less than .05) was the number of bizarre multinucleate giant cells. When the 11 non-tumorigenic lines were ranked by these 2 criteria, 1 non-tumorigenic line (U-251 MGsp) had greater than .95 predicted probability of tumorigenicity. Although further tumorigenicity testing may increase the number of tumorigenic lines, the lines with few "malignant" characteristics may correspond to the population resembling cells of low grade astrocytomas seen within glioblastomas. The histologic pleomorphism of human gliomas is reflected in their morphologic and cell biologic diversity in culture.

The role of radiation therapy in the treatment of supratentorial oligodendrogliomas is controversial. To evaluate the role of radiation therapy, the Duke University Medical Center series was retrospectively analyzed. Clinical history, radiation dosages, and pathologic materials were reviewed. Seventy-one patients were identified as having histologically proven oligodendroglioma. Analysis of the patient population demonstrated it to be similar in all major parameters to other populations previously reported in the literature. Multivariate statistical analysis of the demographic, clinical and radiographic variables of these patients showed that a poorer prognosis was associated with persons of increased age (P = 0.052) and black persons (P = 0.014), and in those with papilledema (P = 0.07), hemiparesis (P = 0.001), intellectual deficits (P = 0.0002), and necrosis (P = 0.041). All patients had a surgical procedure as first treatment while 18 and three patients, respectively, underwent a second and third surgical procedure. Thirty-seven patients had a subsequent course of radiotherapy. Univariate and multivariate statistical analysis comparing the patients treated with surgery alone those treated with surgery plus radiotherapy revealed no significant population or prognostic differences between the groups. The median times until clinical deterioration were 39 versus 27 months, the median times until documented tumor recurrence were 27 versus 28 months and the median survival times were 4.5 versus 5.2 years, for nonirradiated versus irradiated patients. These data, from a large and rigidly evaluated population, demonstrated no statistically significant difference in the symptom-free interval, time until tumor recurrence, or survival between the groups nor did radiation appear beneficial to any subgroup evaluated. The results suggest the need for a prospective clinical trial to evaluate the true role of radiation therapy in the treatment of this tumor.

Two patients with posttraumatic diencephalic seizures, characterized by autonomic dysfunction and extensor posturing, had partial responses to bromocriptine and complete responses to morphine. Probable synergism between the two agents was noted. These 2 cases suggest the potential effectiveness of this regimen for the treatment of diencephalic seizures, raise questions regarding the role of the dopaminergic and opioid systems in this disease entity, and support the hypothesis that diencephalic seizures represent a release phenomenon in the brain.

Cisplatin is a recognized neurotoxic agent that commonly causes ototoxicity and peripheral neuropathy. In conjunction with characteristic peripheral neuropathy, two patients treated with high-dose cisplatin developed Lhermitte's sign, a manifestation of posterior column spinal cord pathology. After cisplatin therapy was stopped, this symptom gradually resolved. This suggests that at high doses cisplatin may also cause demyelinating central nervous system lesions involving the spinal cord.

Memory and language dysfunction has been sporadically reported following stereotaxic thalamotomies. In order to determine which patients are at greatest risk and to better define the nature of this dysfunction, we have prospectively evaluated 18 patients undergoing stereotaxic thalamotomies for movement disorders (MDs). Patients were evaluated clinically, with computed tomography (CT) and with memory and language protocols (MLPs) pre- and postoperatively. Patients exhibiting postoperative deficits were again evaluated with the MLP on follow-up visits to the clinic. Significant changes in memory and language function occurred in 7 out of 18 patients. These 7 patients had diverse etiologies for their MDs. Five of the 18 patients had undergone previous thalamotomies on the contralateral side. Three of these 5 patients with bilateral thalamotomies experienced postoperative functional impairments in memory and language while only 4 of 13 patients with a unilateral thalamotomy experienced these problems. The postoperative functional impairments noted were primarily those requiring orientation and speech. All patients with postoperative memory and language impairments were again evaluated with MLPs months after the operation. In 3 of 7 patients, no improvement was noted, while the remaining 4 did recover to baseline. More severe deficits tended to occur in those patients with ventriculomegaly or evidence of other major cerebral tissue loss by preoperative CT scan and in those patients with lower MLP scores preoperatively. Postoperative memory and language dysfunction was not correlated with the number or size of the lesions made, the postoperative general neurologic examination or CT scans, or the clinical response of the MDs. From our data, it appears that patients with more profound neurologic compromise and/or bilateral involvement as evidenced by poor performance on the MLP, tissue loss on CT scanning, or previous thalamic lesion, are most at risk for memory and language dysfunction postoperatively. However, this dysfunction is not necessarily permanent. Preoperative evaluation with MLPs and CT scanning appear to be of value in predicting those patients at greatest risk for postoperative and language dysfunction.

A patient with painless proptosis and no associated neurologic symptoms was found to have a cystic retrobulbar orbital mass. The initial computed tomography (CT) scan did not demonstrate any intracranial involvement. On orbital biopsy a schwannoma was encountered and repeat CT scan with contrast revealed a large middle cranial fossa mass with extension into the orbit through the optic canal and superior orbital fissure. On lateral transfrontal craniotomy the lesion was noted to arise from the gasserian ganglion and to involve the right cavernous sinus. Subtotal resection was performed, and the patient has remained asymptomatic and free of recurrence for 18 months.

We conducted a Phase II study of combination therapy with vincristine and cyclophosphamide in the treatment of patients with recurrent or metastatic medulloblastoma. Fourteen patients were treated with vincristine 2 mg/m2 (2.0-mg maximal dose) by intravenous bolus on Day 1 and cyclophosphamide 1 g/m2 by intravenous infusion on Days 1 and 2, with cycles repeated every 4 weeks. All 4 patients with extraneural disease (biopsy-proven bony metastases) responded (duration of responses 2+, 6+, 8, and 16+ months) and 4 of 8 evaluable patients with neuraxis disease responded (duration of response 2, 2+, 2+, and 21+ months). Toxicity was limited to neutropenia without any episodes of infection. These therapeutic results compare favorably with other reports of therapy for recurrent medulloblastoma and support the inclusion of vincristine and cyclophosphamide in randomized adjuvant therapy trials of patients with medulloblastoma.

The measurement of electrical impedance of normal and pathologic tissue has not been fully utilized in neurosurgery. This is a report of electrical impedance measurement in the central nervous system of both man and animals. We show the results of the laboratory study done in animals, in the brain and in the spinal cord as well. Also we show the clinical experience of the impedance recordings in the DREZ procedure for some chronic pain conditions, correlating the measurements at the time of the operation with normal conditions, with comments about the findings.