ABSTRACTS

OF

OPEN PAPERS

845 35C Hypothermia Can Reduce Increased Intracranial Pressure as Well as 33C Hypothermia in Patients with Severe Traumatic Brain Injury
Takashi Tokutomi, M.D. Tomoya Miyagi, M.D., Kazuya Morimoto, M.D., Minoru Shigemori, M.D. INTRODUCTION: For many years, we have used therapeutic hypothermia (4872 hr) in patients with severe traumatic brain injury (Glasgow Coma Scale scores of 5 or less). In 2000, we altered the target temperature to 35C from the former 33C, as our findings suggested that cooling to 35C is sufficient to control intracranial hypertension and that hypothermia below 35C may predispose patients to persistent cumulative oxygen debt, which may be associated with an increased risk of complications. In this study, we attempted to clarify whether 35C hypothermia has the same effect as 33C hypothermia in reducing intracranial hypertension and whether it is associated with fewer complications and improved outcomes. METHODS: We compared intracranial pressure and biochemical parameters of the 30 patients treated with 35C hypothermia (January 2000June 2005) with those of the 31 patients treated with 33C hypothermia (July 1994December 1999). RESULTS: Patient characteristics were similar in the two groups. The mean intracranial pressure on Days 1 to 7 after injury were 15.3 9.6 to 20.1 9.0 mmHg in the 35C hypothermia group and 14.9 10.2 to 20.7 12.7 mmHg in the 33C hypothermia group (P 0.0669 to 0.9903). The incidence of intracranial hypertension ( 20 mmHg) on Days 1 to 7 was 18 to 39% and 18 to 37% of measurements in the 35C and 33C groups, respectively (P 0.14440.9930). Furthermore, our 35C hypothermic patients exhibited a significant improvement in the decline of systemic oxygen consumption and serum potassium concentrations during hypothermia, and in the increment of C-reactive protein after rewarming. Although the mortality rate tended to be lower in the 35C group (27 versus 48%, P 0.0801), there were no statistically significant differences in the incidence of systemic complications. CONCLUSION: The effects of 35C hypothermia on intracranial hypertension are similar to those of 33C hypothermia.

sacrificed 35 days after injury and brain sections were stained with immunohistochemistry. RESULTS: No improvement in neurological function was observed in the TBI saline and TBI scaffold groups; whereas significant improvement was seen in the TBI hMSC and TBI scaffold/hMSC groups. However, functional improvement was significantly more in the TBI scaffold/hMSC group than in the TBI hMSC group. Histological examination revealed that treatment with scaffold/ hMSCs significantly reduced lesion volume, whereas no change in lesion volume was seen in the other three groups. In addition, although hMSCs were seen in the lesion boundary zone of both the TBI scaffold/hMSC and TBI hMSC groups, their number was significantly more in the TBI scaffold/hMSC group showing that scaffolds enhance the engraftment of hMSCs. CONCLUSION: Our data demonstrate that scaffolds suffused by hMSCs improve spatial learning and sensorimotor function, and reduce the lesion volume as well as increase the number of hMSCs into the lesion boundary zone after TBI compared to saline-, scaffold- and hMSC-treated rats.

847 Intrathecal Transplantion of a Human Neuronal Cell Line for the Treatment of Neuropathic Pain in a Spinal Cord Injury Model
Stacey C. Quintero Wolfe, M.D., Nadia Cumberbatch, Miguel Martinez, B.S., Mary Eaton, Ph.D. INTRODUCTION: After spinal cord injury (SCI), inhibitory neurotransmitter levels are decreased below the level of injury, causing an imbalance between inhibitory and excitatory sensory signaling. Without descending or local inhibition, excitatory pathways such as A-delta and C pain fibers predominate, leading to hypersensitivity and neuropathic pain. SCI that induces behavioral hypersensitivity can be reproduced in a rat model, using an intraspinal injection of the glutamate receptor agonist, quisqualic acid (QUIS). This model results in neuronal loss in the dorsal horn laminae with spontaneous (excessive grooming) and evoked (mechanical allodynia and thermal hyperalgesia) behaviors associated with neuropathic pain. We have isolated and characterized a subclone of the human NT2 cell line, hNT2.17, which differentiates to a neuronal phenotype that secretes inhibitory neurotransmitters such as -aminobutyric acid and glycine. When transplanted into the subarachnoid space of SCI rats, this cell line results in complete recovery from behavioral hypersensitivity after QUIS. METHODS: Male Wistar-Furth rats (n 12/group; Group 1, Nave; Group 2, QUIS-alone; Group 3, QUIS viable cell transplant; Group 4, QUIS nonviable cell transplant) underwent QUIS injury followed by intrathecal transplantation of viable and nonviable cells (2 wk after QUIS). Behavioral testing (mechanical allodynia and thermal hyperalgesia) was performed weekly for 8 weeks. Evaluation of optimal dose was also assessed by transplanting viable cells in varying doses (1000, 100,000, and 1,000,000 cells; n 8/group) in a separate experimental group. RESULTS: Animals undergoing viable hNT2.17 cell transplantation demonstrated complete reversal of all hypersensitivity (P 0.05). The recovery occurred 1 week after transplantation and was maintained for the entire experiment. Immunohistochemistry confirmed that grafted cells were present and synthesizing -aminobutyric acid. The optimal dose for complete and durable behavioral recovery was one million cells per transplant graft.

846 Collagen Scaffolds Populated with Human Marrow Stromal Cells Reduce Lesion Volume and Improve Functional Outcome after Traumatic Brain Injury
Asim Mahmood, M.D., Dunyue Lu, M.D., Ph.D., Changsheng Qu, M.D., Michael Chopp, Ph.D. INTRODUCTION: This study was designed to investigate the ability of collagen scaffolds populated with human marrow stromal cells (hMSCs) to reduce lesion volume and improve functional outcome after traumatic brain injury (TBI) in rats. No treatment has been found to be effective in repairing structural loss after TBI. METHODS: Ultrafoam scaffolds, collagen Type I were obtained from commercial sources and were impregnated with 3x106 hMSCs. Male Wistar rats (n 24) were injured with controlled cortical impact and divided into four groups. The first group (TBI scaffold/hMSC) was transplanted with collagen scaffolds populated with hMSCs into the lesion cavity 4 days after TBI. The other three groups were transplanted with saline (TBI saline), scaffolds only (TBI scaffold) or hMSCs only (TBI hMSC). Functional outcome was measured using neurological severity scores and Morris Water Maze. All rats were

NEUROSURGERY

VOLUME 59 | NUMBER 2 | AUGUST 2006 | 469

ABSTRACTS

OF

OPEN PAPERS

CONCLUSION: The inhibitory neuronal cell line, hNT2.17, is a ready source of human cells that potently reverses neuropathic pain of SCI origin and can be used clinically, without the deleterious side effects of current pharmacotherapy.

848 Constitutive -Aminobutyric Acid Expression via a Recombinant Adeno-associated Virus Consistently Attenuates Neuropathic Pain
Jin-Woo Chang, M.D., Jaehyung Kim, B.A., Boyoung Lee, Ph.D., Huiran Lee, Ph.D. INTRODUCTION: Peripheral neuropathic pain, characterized by a wide spectrum of pathological processes, is composed of a number of phenomena occurring at different sites and times, depending on disease states. Among the complex mechanisms underlying neuropathic pain, partial nerve injury seems to result in a selective loss of -aminobutyric acid (GABA)-ergic inhibitory synaptic currents in the spinal cord. This feature then contributes to the phenotypes of the neuropathic pain syndrome. GABA, the product driven by glutamate decarboxylase (GAD), is a main inhibitory neurotransmitter in the dorsal horn of the spinal cord and also plays an important role in the ventral horn. METHODS: Previously, we constructed rAAV-GAD65, which expresses significantly higher amount of GAD65 and GABA, than controlled by the universal CMV promoter. To investigate the beneficial effects of rAAV-GAD65 treatment, we established a neuropathic pain rat model by tibial and sural transection. RESULTS: The direct administration of rAAV-GAD65 to dorsal root ganglias induced the constitutive GAD65 expression, which could be readily detected by immunocytochemistry. Both allodynic and hyperalesic behavior tests suggested that neuropathic pain markedly decreased, along with the transgenic GAD65 expression. Moreover, the magnitude of the pain relief maintained for entire experimental period, where GAD65 expression was also noticed with no substantial reduction in its immunoreactive intensity. Finally, the significant amount of enhancement in GABA release after rAAVGAD65 delivery was identified in vivo by high-performance liquid chromatography. CONCLUSION: Taken together, the data suggest that the persistent GAD65 expression and subsequent GABA release in dorsal root ganglias via rAAV can effectively attenuate peripheral neuropathic pain for long period of time.

surgery. MCS was performed in two stages. During the first stage, an epidural electrode was implanted over the motor region corresponding to the pain topography. A minimum 1-week stimulation trial was conducted to determine analgesic effectiveness. During the second stage, patients with a significant reduction in pain were implanted with an internal pulse generator for long-term stimulation. Patients who did not derive adequate benefit underwent removal of the electrodes. Pre- and postoperative pain scores were recorded in all patients and all patients were asked to estimate the percent pain reduction derived from stimulation. RESULTS: Pain diagnoses were as follows: trigeminal neuropathic/ deafferenation pain (n 17), post-stroke pain (n 8), Post-herpetic neuralgia (n 1), and phantom limb pain (n 1). The average duration of symptoms before surgery was 5 years. The average follow-up after surgery has been 2 years. For the entire group, the average pre- and postoperative visual analog scale scores were 8.7 and 4.5, respectively. The average subjective pain reduction was 40%. For the 19 patients implanted permanently, average visual analog scale scores were reduced from 7.4 to 2.7. The average visual analog scale score at the most recent follow-up examination was 3.8, with an estimated pain reduction of 49%. There were no surgical complications. Three patients experienced an isolated seizure during IPG programming. CONCLUSION: MCS produces effective pain relief in selected patients with intractable deafferentation pain conditions.

850 Three Column Contact Patterns for Spinal Cord Stimulation Offer Selective Dorsal Column Fiber Activation
Wilbert Wesselink, M.Sc., Richard B. North, M.D. INTRODUCTION: Implantable stimulation systems now drive as many as 16 independent contacts and can support multiple columns for spinal cord stimulation, so as to control for anatomical asymmetry and provide better paresthesia coverage. Three percutaneous catheter electrodes (leads) can be used, with one 1 x 8 compact lead and a bifurcated extension connecting two standard 1 x 4 leads, forming a unique 48-4 pattern. Similar contact patterns can be fabricated as a paddle array for surgical implantation. Contact configurations may be compared in a computer model, as to their ability to activate dorsal column (DC) versus dorsal root (DR) fibers and energy usage, while controlling for depth of cerebral spinal fluid (dCSF), spacing between leads and off midline placement. METHODS: The University of Twente computer model was used to predict the effects of electrical stimulation using various contact combinations and geometries. The modeled configurations (including an unguarded bipole (UB) or guarded cathode tripole (GC) on a single lead, and transverse (TTS) or longitudinal (LTS) tripole-like stimulation groups on three leads. RESULTS: For the two values of dCSF modeled, the lowest voltage needed for activation of the DC fibers is obtained with LTS patterns, followed by GC, UB, and TTS. The best activation ratio of DC to DR occurs with TTS followed by GC, LTS, and UB. TTS models show that DC to DR ratio is minimally impacted by increased spacing between the two lateral and midline leads out to 3 millimeters edge-to-edge separation. Power needs increase as the spacing narrows. CONCLUSION: TTS offers the best guarded configuration, activating fibers deeper in the DC before recruitment of DR fibers. LTS offers the best guarded configuration when attempting to reduce the voltage

849 Motor Cortex Stimulation for Chronic Intractable Deafferentation Pain

Richard K. Osenbach, M.D. INTRODUCTION: Deafferentation pain syndromes are among the most treatment-refractory pain conditions known. Motor cortex stimulation (MCS) has become an accepted procedure for the most refractory patients. We report our initial experience with MCS in 27 patients. METHODS: The charts of all patients who underwent a trial of MCS between 1998 and the present were reviewed. All patients experienced chronic intractable pain that was refractory to standard pharmacological therapy including opioids. All patients underwent pretreatment evaluation by an experienced pain psychologist before

470 | VOLUME 59 | NUMBER 2 | AUGUST 2006

www.neurosurgery-online.com

ABSTRACTS

OF

OPEN PAPERS

needed to activate DC fibers. Lateral separation is optimal at 2 to 3 mm.

851 Results of Repeat Posterior Fossa Exploration for Patients with Medically Intractable Trigeminal Neuralgia
Nelly Amador, M.D., Deborah A. Gorman, R.N., Bruce E. Pollock, M.D. INTRODUCTION: Trigeminal neuralgia patients with persistent or recurrent face pain after microvascular decompression (MVD) typically undergo less invasive procedures in the hope of providing pain relief. The outcomes and risks of repeat posterior fossa exploration (PFE) for these patients are not as clearly understood. METHODS: From September 1999 to February 2006, 27 patients (12 men, 15 women) underwent repeat PFE. The median interval between the PFEs was 5.9 years (range, 4 d39 yr). Sixteen patients (62%) underwent one or more other surgeries (median, one surgery) between the PFEs (glycerol rhizotomy, n 10; radiofrequency rhizotomy, n 9; stereotactic radiosurgery, n 9; balloon microcompression, n 6; peripheral neurectomy, n 2). Twenty-one patients (78%) had Burchiel Type 1 pain, whereas six patients had Burchiel Type 2 pain (22%). The median follow-up period after surgery was 26 months. RESULTS: Compression of the trigeminal nerve was noted by an artery (n 13, 48%), vein (n 4, 15%), or Teflon (n 4, 15%). Notably, four patients (15%) had the cranial nerve seventh-eighth complex decompressed at their first surgery. An MVD was performed in 15 patients (56%) and a partial nerve section performed in 12 patients (44%). An excellent facial pain outcome (no pain, no medication) was achieved and maintained for 79 and 48% of patients at 1 and 3 years after surgery, respectively. Sixteen patients (59%) had new or increased facial numbness. Two patients (8%) developed anesthesia dolorosa. One patient was deaf after surgery and no patient developed facial weakness. CONCLUSION: Repeat PFE can be performed safely and has facial pain outcomes comparable to percutaneous needle-based techniques and stereotactic radiosurgery. Patients with persistent or recurrent trigeminal neuralgia should be considered for repeat PFE if they are younger or medically well, especially if other surgeries have not relieved their facial pain.

who were treated with a median dose of 80 Gy with one 4-mm isocenter between October 13, 1999 and November 18, 2002. Patients were placed in five groups based on categories of decreasing success: Group 1A, complete pain relief and off medications; Group 1B, complete pain relief and less or same medications; Group 1C, 50% or greater pain relief and off medications; Group 1D, 50% or greater pain relief and less or same medications; and Group 2, less than 50% pain relief and/or more medications. Patients in Groups 1AD were collectively placed under the umbrella of a successful treatment. Patients in Group 2 were considered a treatment failure. RESULTS: Sixty-four percent of patients had a successful treatment with a mean follow-up period of 48 months (range, 3666 months). The data was subcategorized as follows: Group 1A, 34%; Group 1B, 4%; Group 1C, 4%; Group 1D, 23%; and Group 2, 36%. Further data analysis showed no differences in outcomes between patients previously treated with microvascular decompression or rhizotomy versus patients with no previous surgical treatments. Thirty-six percent of patients reported some degree of post-treatment facial numbness. No patients lost a corneal reflex or developed anesthesia dolorosa. CONCLUSION: In our series of 53 patients with a mean follow-up period of 48 months, 64% of patients had a successful treatment. Thirty-four percent of patients had what we define as a perfect outcome, that is, they had no pain and required no medications.

853 Postoperative Continuous Paravertebral Anesthetic Infusion for Pain Control in Lumbar Spinal Fusion Surgery: A Case-control Study
James B. Elder, M.D., Michael Y. Wang, M.D. INTRODUCTION: Patients who undergo lumbar spine procedures frequently experience significant, debilitating pain related to their surgery. This pain may delay postoperative mobilization, increase length of hospitalization, and require the prolonged use of high doses of narcotics. Use of a local anesthetic continuous-infusion pump after surgery may lead to improvement in these outcome variables. METHODS: After posterior lumbar spine fusion procedures, 26 consecutive patients received continuous infusion of 0.5% marcaine into the subfascial aspects of the wound via an elastomeric pump. Data were collected prospectively by third party assessment using standard nursing protocols. This included pain scores and opiate use over the first 5 postoperative days, length of hospitalization, and complications. Retrospective analysis compared each study patient to a case-control patient. Variables such as age, gender, and surgical procedure were similar between matched cases. RESULTS: Patients receiving continuous local anesthetic infusion used 21.5% less narcotics on postoperative Day 1, 37.4% less on Day 2, and 26% less on Day 3 compared with control patients. Differences in opiate usage were negligible on postoperative Days 4 (0.04% greater) and 5 (0.07% greater). A lower average pain score was observed among the study patients on each postoperative day: 23.9% less pain on Day 1, 19.0% on Day 2, 17.8% on Day 3, 16.8% on Day 4, and 40.4% on Day 5. No differences were observed in the length of hospitalization or complications. CONCLUSION: Patients with a local anesthetic continuousinfusion device used less narcotics than case-control patients over the first 3 postoperative days and reported lower pain scores during the first 5 postoperative days. These results suggest that continuous infusion of local anesthetic into the paravertebral tissue during the immediate postoperative period is a safe and effective technique that

852 Long-term Outcomes for Trigeminal Neuralgia after Gamma Knife Radiosurgery
Ron I. Riesenburger, M.D., Vasilios A. Zerris, M.D., M.Med(S), Kevin C. Yao, M.D. INTRODUCTION: Most studies published on outcomes after gamma knife radiosurgery (GKS) for trigeminal neuralgia (TN) have relatively short-term follow-up. The few studies that have longer median follow-up periods often include outliers with relatively shortterm follow-up as well. These short-term outliers are more likely to report successful outcomes, which may skew results and make socalled long-term outcomes seem more favorable than they really are. In reviewing our series, we restricted follow-up to a minimum of 36 months and rigorously analyzed long-term outcomes for patients with TN after GKS. METHODS: We reviewed 53 patients with typical, intractable TN

NEUROSURGERY

VOLUME 59 | NUMBER 2 | AUGUST 2006 | 471

ABSTRACTS

OF

OPEN PAPERS

achieves lower pain scores and narcotic use. Further data may reveal additional benefits, such as decreased times to mobility and functional independence.

854 Optimizing Surgical Exposure for Neurosurgical Trainees with Limited Working Hours
Lewis Thorne, F.R.C.S., Simon Shaw, F.R.C.S., Sasha Burns, F.R.C.S., R. Bradford, Joan P. Grieve, M.D. INTRODUCTION: National and European labor agreements have forced a reduction in trainees working hours in all medical specialties. The conflict between training and service provision needs to be rationalized to ensure an adequate level of training for the next generation of neurosurgeons. The majority of emergency operations require generic skills that are rapidly learned. The most technically demanding procedures tend to be elective. To determine the most effective working pattern for neurosurgical trainees after implementation of reduced working hours we compared operative exposure for various working patterns. METHODS: We conducted an audit of operative data over a 6-month period. Six trainees in our unit were placed on two virtual rotations compliant with existing regulations: 1) full shift with 1 week of 12 hours of night duty with no day duty and the following week taken as compensatory leave and 2) maximal partial shift with a 24-hour duty period followed by a day off in compensation. The aim was to determine what their operative experience would have been over a 6-month period. RESULTS: Trainees on a partial shift rotations would have performed a similar number of emergency operations (average, 9; range, 517), as those on a full shift (average, 11; range, 417). Trainees on the maximal partial shift missed 10 (range, 323) elective cases, compared with 18 (1031) over the same period for those on full shift, as a result of enforced absence following periods of duty. These included posterior fossa, complex spinal, benign, and rare cranial procedures. Comparison with a trainee in the 1980s over a period of the the same duration will also be presented. CONCLUSION: There now exists a finite period for training to attending level to take place. Careful manipulation of the time available within imposed constraints is essential to ensure that tomorrows neurosurgeons are competent in facing the complex challenges of modern neurosurgery.

METHODS: A decision analysis model with a time horizon of 6 months was developed to compare expected costs and outcomes of three different strategies for DVT detection in aSAH patients: 1) Doppler USG screening of all patients before discharge from the intensive care unit, 2) Doppler USG screening of only Hunt and Hess Grade III to V patients, and 3) no screening. Doppler USG was performed on all patients when clinically indicated. A retrospective review of 178 aSAH patients who underwent screening before discharge from the intensive care unit was performed to determine the prevalence of DVT. Additional probabilities and costs (adjusted to 2004 dollars) were obtained from the literature. The primary outcome was the incremental cost-effectiveness ratio. Several variables were tested in one- and two-way sensitivity analysis. RESULTS: In the base case analysis, the expected cost of screening Strategy 1 was $618 per patient; screening Strategies 2 and 3 had expected per patient costs of $419 and $157, respectively. The more expensive programs were associated with small decreases in expected quality of life and were, therefore, dominated by the no screening strategy. This result was preserved in sensitivity analysis across a wide range of values for prevalence of DVT and testing characteristics of Doppler USG. CONCLUSION: A strategy of obtaining Doppler USG only for clinically suspected DVT in patients after aSAH was found to be dominant in our model, as it was both less expensive and associated with higher expected quality of life. This result was robust to variations in the base case assumptions.

856 Prospective, Multicenter Evaluation of Neurosurgical Emergency Transfers in Cook County, Illinois
Richard W. Byrne, M.D., Bradley T. Bagan, M.D., Konstantin Slavin, M.D., Daniel Curry, M.D., Tyler R. Koski, M.D., Thomas C. Origitano, M.D. INTRODUCTION: A significant increase in the number of emergency neurosurgical transfers has been noted at academic centers in Cook County, Illinois. To determine the cause, a phone survey demonstrated a decline in neurosurgery emergency coverage from 44 to 84% of Cook County community hospitals over the past 10 years. To quantify the resulting increase in emergency transfers, determine the time lapse in transfer, and evaluate the impact on patients, a transfer study involving all five academic centers in Cook County was performed. METHODS: A multicenter, prosective evaluation of neurosurgical emergency transfers to Rush, Loyola, University of Illinois, University of Chicago, and Northwestern was performed for 2 months in 2005. Institutional review board approvals were obtained. All relevant data regarding each transfer was collected, including transfer time (defined as time lapse from computed tomographic/magnetic resonance imaging scan diagnosis to arrival at the accepting institution). RESULTS: Two hundred thirty emergency transfers were accepted by the five institutions over the study period. Seventy percent of these patients had intracranial hemorrhages; 74% of patients were transfered from hospitals without neurosurgery coverage. The mean time lapse from imaging diagnosis to arrival at the accepting institution was 5.04 hours (standard deviation, 3.5 hr). Twelve percent of patients showed a decline in Glasgow Coma Scale score during transfer. Five percent of patients showed a decline of greater than 5 Glasgow Coma Scale points during transfer, despite being transferred faster than patients without Glasgow Coma Scale decline (P 0.021).

855 Is Screening for Deep Venous Thrombosis in Aneurysmal Subarachnoid Hemorrhage Patients Cost Effective?
William J. Mack, M.D., Zachary L. Hickman, B.S., E. Sander Connolly, Jr., M.D., Peter D. Angevine, M.D. INTRODUCTION: Cranial surgeries, extended periods of immobilization, and significant medical comorbidities put aneurysmal subarachnoid hemorrhage (aSAH) patients at risk for deep venous thrombosis (DVT). Few data exist, however, regarding the cost-effectiveness of screening for asymptomatic DVTs to prevent adverse events in this patient cohort. We assessed cost-effectiveness of DVT screening by Doppler ultrasonography (USG) in aSAH patients before discharge from the intensive care unit.

472 | VOLUME 59 | NUMBER 2 | AUGUST 2006

www.neurosurgery-online.com

ABSTRACTS

OF

OPEN PAPERS

CONCLUSION: Cook County, including Chicago, is now an underserved area in neurosurgical emergency care. This access to care issue and connections to the recent liability crisis in Illinois will be discussed. Delays in transfer to a center with neurosurgical coverage are long (mean, 5 hr after diagnosis) despite efforts to expedite transfers. As a result, 5% of patients experience dramatic deterioration during transfer. Further data collected in the study may point to underlying causes of transfer delays and possible solutions.

857 First to Worst: Does Diagnosis-related Group Assessment of Hospital Mortality Indicate Quality?
Carl B. Heilman, M.D., Steve Hwang, M.D. INTRODUCTION: In 2003, Tufts New England Medical Center (T-NEMC) had the lowest mortality of all hospitals for patients admitted with the diagnosis-related group diagnosis of stroke in the state of Massachusetts. In 2004, T-NEMC had the second highest stroke related mortality in the state. This presentation will evaluate the stroke-related mortality in patients admitted in 2004 with a diagnosis-related group diagnosis of stroke, to assess whether this determination of quality is useful for assessing the delivery of health care. METHODS: The charts of 31 patients who died at T-NEMC in 2004 of stroke-related mortality were reviewed. The cause of death was determined in each case with specific attention to the quality of care provided. Whether patients were comfort measures only or do not resuscitate at the time of death was also assessed. RESULTS: In 2004, 31 in-hospital deaths occurred in 205 patients admitted to T-NEMC with a diagnosis-related group diagnosis of stroke. Included among these 31 patients were 19 with nonoperative massive intracerebral or subdural hemorrhage, four patients with Hunt and Hess Grade 5 subarachnoid hemorrhage, four patients with massive ischemic stroke, one elderly patient with a small intracerebral hemorrhage with intraventricular extension, one demented patient with multiple infarcts, and two other patients. Of the 31 patients who died, 26 were either comfort measures only or do not resuscitate at the time of death. An additional three patients died of brain death and another patient was in the process of becoming comfort measures only by family discussions. In only one patient was there an error in the delivery of medical care. Medical treatments that could have prevented an in-hospital death, but not improved quality of life, will be discussed. CONCLUSION: There is increasing interest in the quality of health care. Quality will be used to determine patient referrals, insurance contracts, and rating individual physicians. However, using hospital mortality rates by diagnosis-related group in stroke patients probably is not a good measure of quality. Neurosurgery needs to develop means for determining true measures of quality in health care delivery.

METHODS: A retrospective cohort study was performed using the Nationwide Inpatient Sample, 19972003. Multivariate logistic regression was used to model selection for surgical PD treatment with generalized estimating equations used to adjust for within-hospital clustering. RESULTS: A total of 2460 patients with diagnosed PD underwent surgical treatment at 96 hospitals (1883 neurostimulator, 577 thalamotomy/pallidotomy). Of surgically treated patients, only 0.7% were African-American. Comparatively, 12% of the United States population is African-American, and the incidence of PD for Americans of European and African heritage is estimated to be similar (13.6 and 10.2 per 100,000 persons/year, respectively). We compared surgically-treated patients to 11,242 patients with PD admitted to the same hospitals who did not receive surgical PD treatment to determine patient-related factors associated with treatment. Adjusted for age, treatment year, and expected primary payer, African-Americans had a significantly lower chance of receiving any surgical PD treatment (odds ratio, 0.29; 95% confidence interval, 0.180.49; P 0.001) or receiving a neurostimulator (odds ratio, 0.29; 95% confidence interval, 0.170.49, P 0.001). Of African-American patients, 52% were admitted to hospitals performing fewer than four cases per year, compared with 34% for other patients (P 0.001). In contrast to surgical PD treatment, African-American inpatients were more likely to receive gastrostomy (12%), another common surgical procedure in PD, suggesting that not all surgical procedures are underrepresented in this population. Finally, patients with private or Medicare insurance were more likely to receive surgical PD treatment and neurostimulator placement than Medicaid patients (P 0.01 and 0.03, respectively). CONCLUSION: These findings suggest that African-American patients with PD are significantly less likely to receive neurosurgical PD treatment of any kind, including neurostimulator placement. Certain types of medical insurance are also significantly associated with treatment selection. Factors that may play a role in these disparities include referral patterns, patient preferences, socioeconomic status, and physician bias.

859 Is the Current Model of Academic Neurosurgery Sustainable?

Dongwoo J. Chang, M.D. INTRODUCTION: At the October 2005 Congress of Neurological Surgeons meeting, the author preliminarily reported on a 125neurosurgeon survey on the current status of academic neurosurgery. Based on the reported data, there was clear evidence of a disconnect between the traditional missions of academic neurosurgery and the practical realities of functioning as a neurosurgical academician. The author now reports further on the analyzed data and suggests an alternative funding plan as a way to actualize the goals of the traditional academic missions. METHODS: Confidential Email questionnaires were sent to fulltime academic neurosurgeons in the United States. RESULTS: The vast majority of academic neurosurgeons are not subspecialized (with most of the subspecialized neurosurgeons focused on spine) and spend most of their time in direct patient care. This is compounded by minimal neurosurgery resident involvement in the outpatient clinic and suboptimal resident involve-

858 Racial and Socioeconomic Disparities in the Surgical Treatment of Parkinson Disease in the United States, 19972003
Ziv Williams, M.D., William T. Curry, Jr., M.D., Emad N. Eskandar, M.D., Frederick G. Barker, M.D. INTRODUCTION: We examined possible disparities in surgical Parkinson disease (PD) treatment relative to racial and socioeconomic patient variables.

NEUROSURGERY

VOLUME 59 | NUMBER 2 | AUGUST 2006 | 473

ABSTRACTS

OF

OPEN PAPERS

ment surgical procedures. Seventy-six percent of the academic neurosurgeons reported significant institutional pressure to increase professional billings, whereas most (82%) spent less than 15% of their total work time on research and writing. Interestingly, most academic neurosurgeons preferred salary compensation based on clinical productivity and promotions based on scholarly contributions. CONCLUSION: The current academic neurosurgical model is unsustainable, particularly in the modern era of medical economics. A direct conflict of interest is created because concrete rewards are given primarily for billable work, even though, in academia, all missions should have great emphasis. The author suggests a publiclyfunded model of academic neurosurgery that would allow compensation on mission-based activities, similar to the Alternative Funding Plan being used by some of the Canadian regional academic health centers. A publicly-funded mandate would make the greater society accountable for the future vitality of the neurosurgical discipline rather than letting academic neurosurgeons sink or swim in an unsustainable situation in an era rampant with financial, legal, and logistical pressures.

861 Pediatric Back and Neck Pain: Pathology, Treatment, and the Role of the Pediatric Neurosurgeon
Kevin L. Stevenson, M.D., Gina D. Mangin, PA-C, Keith C. Raziano, M.D., Selene White, L.P.N., Durga Shah, P.T. INTRODUCTION: Spine pain in the pediatric and adolescent age groups is becoming increasingly common. Despite significant advances in the understanding and treatment of adult spinal disorders, the literature concerning pediatric back and neck pain is sparse. This study examines the presentation, etiology, and treatment of pediatric spine pain. METHODS: Two hundred fifty consecutive patients were seen at a multidisciplinary pediatric spine center. Patients were evaluated and managed by a team consisting of a pediatric neurosurgeon, a pediatric interventional spine physician, and a pediatric physical therapist. Standardized questionnaires were used to collect historical and subjective data. Team consensus determined physical examination findings, diagnosis, and treatment. RESULTS: One hundred ninety patients (76%) had a chief complaint of spine pain at an average age of 13.23 years. Trauma was noted in 38.42%, with motor vehicle collisions being the most common inciting event (31.51%). Thoracic pain was less common than cervical or lumbar (12.11 versus 37.89 and 39.47%), but more commonly associated with surgical pathology. Neurological deficits were found in 25.26%, most commonly sensory (47.92%). Before referral, 48.42% had undergone at least one magnetic resonance imaging scnas, whereas only 11.05% had undergone physical therapy. On average, pain had been present for 8.81 months before referral, during which 50% noted a negative effect on physical activity and 23.16% noted a negative effect on school performance. The most common diagnosis was myofascial pain (33.68%) followed by lumbar herniated disc (13.68%). Chronic myofascial pain was aggressively treated and 95.31% noted improvement with stabilization therapy and electrical muscle stimulation. Surgical pathology was found in 26.84%, most commonly herniated lumbar disc and C1C2 instability. CONCLUSION: Pediatric spine pain is common. Aggressive treatment of myofascial pain is highly effective. More than one-quarter of the children with spine pain will harbor surgical pathology, which demands a central role for pediatric neurosurgeons in the evaluation and management of pediatric spine pain.

860 Effects of Socioeconomic and Geographic Variations on Survival for Adult Glioma in England and Wales: A Population-based Study
Ming-Yuan Tseng, M.D., M.Sc., M.Med. (S), Ph.D., Jen Ho Tseng, M.D., Edwin Merchant, B.A. INTRODUCTION: To investigate effects of socioeconomic status (SES) and geographical variations on survival for adult patients with glioma, data of 30,489 patients from the Cancer Registry in England and Wales are analyzed. METHODS: Median survival and crude survival rates for eight variables (age, sex, International Classification of Diseases for Oncology (ICD-O) morphology, World Health Organization (WHO) grade, tumor site, SES, geographical regions, and periods of diagnosis) are calculated using the Kaplan-Meier method. Distributions among different variables are compared using the 2 test. Cox multivariate regressions are performed for estimating hazards ratios (HR) to death. RESULTS: The median survival and the 1, 5, and 10-year crude survival rates in this population are 0.42 years, and 29.1, 12.0, and 7.7%, respectively. There is a gradient in SES from the south to the north ( 2 test, P 0.001) and a gradual increment in higher SES from the early to the recent period ( 2 test, P 0.001). Mono- and multivariate analyses reveal that the survival is influenced by all eight variables (P 0.05). Age (HR, 1.04/year from 15 years, P 0.001), WHO grade (1.21/grade from Grade I, P 0.001), and ICD-O morphology (HR, 1.231.89, compared with ependymoma, P 0.05) are the three most powerful factors. However, there are independent effects of SES (HR, 1.03/quintile of deprivation, P 0.001) and geographical regions (HR, 1.10 for outside the Southern England, P 0.001) on survival for these patients. CONCLUSION: Although age and tumor characteristics (ICD-O morphology, WHO grade, tumor site) are well-known prognostic factors determining the survival for adult patients with glioma, SES and geographical variations also play significant roles. For more costeffective allocation of health resources, investments on these two modifiable factors should be considered.

862 Thoracolumbar and Sacral Spine Injuries in Children and Adolescents: A Review of 89 Cases
Seref Dogan, M.D., Sam Safavi-Abbasi, M.D., Nicholas Theodore, M.D., Nitin R. Mariwalla, B.A., Eric M. Horn, M.D., Ph.D., Volker K.H. Sonntag, M.D. INTRODUCTION: Few reports deal specifically with pediatric thoracic, lumbar, and sacral injuries. Guidelines for the management of these injuries are missing. This study reviews our experience with these injuries in children to determine the mechanism, patterns of injury, and factors affecting management and outcome. This represents the largest study of its kind in the literature. METHODS: Between 1997 and 2005, 89 (46 boys and 43 girls; mean age, 13.2 yr; range, 316 yr) patients with thoracic, lumbar, and sacral injuries (total of 141 fractures) with and without spinal cord injury were treated. Eighty-two were between 9 and 16 years of age, and

474 | VOLUME 59 | NUMBER 2 | AUGUST 2006

www.neurosurgery-online.com

ABSTRACTS

OF

OPEN PAPERS

seven were between the ages of 3and 9 years. We evaluated the level and pattern of injury, diagnosis, neurological function (Frankel grade), associated injuries, radiographic findings, and outcomes. Follow-up assessment included clinical evaluation and radiographic studies. RESULTS: Injuries included fracture, fracture/dislocation, dislocation, and ligamentous injury. The lumbar region was most frequently involved while the sacrum was the least frequently involved. Overall, 90% of patients were neurologically intact, 3.3% had incomplete spinal cord injury, and 6.7% had complete spinal cord injury. Treatment was nonsurgical in 66 (74%) of the patients, and surgery was performed in 23 (26%) patients (anterior approach in six, posterior approach in 16, and a combined approach in one patient). Stable fixation and maintenance of alignment were demonstrated in all 23 patients who underwent surgical treatment. Postoperatively, four patients (30.7%) with neurological deficits improved. CONCLUSION: Thoracic and lumbar spine injuries occur most commonly in children older than 9 years of age and are mainly located at L2L5. Multilevel injuries are common and warrant radiological workup of the entire spinal column. Most patients can be treated conservatively, although both posterior and anterior approaches are effective. Patients with spinal cord or multilevel injuries can develop spinal deformity and should be followed closely.

864 Medulloblastoma Subtypes Defined by Gene Expression Analysis

Manuel Ferreira, M.D., Ph.D., Scott L. Pomeroy, M.D. INTRODUCTION: Medulloblastomas are the most common type of malignant pediatric brain tumor. After surgery, therapy consists of highdose chemotherapy and cranial-spinal radiation. Survival is associated with neurological sequelae owing to this aggressive therapy. Histopathological classification of medulloblastomas into the desmoplastic or classic subtypes has not been found to correlate with outcome, whereas clinical criteria have (e.g., metastasis). This usually guides postoperative treatment. Our group showed gene expression profiling to be highly predictive of response to therapy, predicting outcome with much greater accuracy than current staging criteria. This proved to be an accurate way of differentiating between certain embryological brain tumors (teratoid, rhabdoid, peripheral neuroectodermal, glioma, and medulloblastoma). This could become a way, based on the genetic fingerprint of a medulloblastoma, for risk stratification. METHODS: We used deoxyribonucleic acid microarray gene expression data (Affymetrix HuGeneFL 6800 arrays) from 74 medulloblastomas, five central nervous system teratoid/rhabdoid tumors, 10 malignant gliomas, and four normal cerebellums. Analysis was performed by principal component analysis, non-negative factorization (NMF) and gene set enrichment analysis. RESULTS: This method of classification proved useful when differentiating between embryological tumor types. Using NMF analysis from 74 medulloblastomas, we found that they segregated into five subgroups. One group (NMF1) was made up of the desmoplastic tumors in the dataset. The classic tumors were divided into four distinct subgroups (NMF2NMF5). We applied gene set enrichment analysis methodology to the five NMF classes and found that the sonic hedge hog signaling pathway was enriched in NMF1, consistent with our previous work. The other NMF groups comprising classic tumors were identified by signature gene sets. CONCLUSION: By using deoxyribonucleic acid microarray expression data, we identify subgroups of medulloblastomas that are differentiated based on their genetic fingerprint. This may prove invaluable for guiding therapy (risk stratification), quick assaying for risk stratification at the time of diagnosis, new molecular targets, and drug discovery.

863 Is Multifocal Seizure Resection in Children Reasonable?

David M. Frim, M.D., Kurt Hecox, M.D., Ph.D., Michael Kohrman, M.D., Charles Marcucilli, M.D., Ph.D., Michael Turner, M.D. INTRODUCTION: Resective seizure surgery is generally applied to monofocal, rather than multifocal, epilepsy. However, in pediatric patients in whom developmental issues and the ability to perform daily activities is of great importance, palliative surgery that reduces, but does not eliminate, seizure activity can improve function (e.g., allow school attendance). This result can be of great value. We used this philosophy to approach a cohort of children with two or more seizure foci by resecting multiple foci and evaluating outcome. METHODS: Charts of 50 consecutive children who underwent subdural electrode electroencephalographic monitoring followed by second surgery for seizure focus resection were reviewed. Three patients were lost to long-term follow-up. RESULTS: Nineteen patients underwent resection of two or more foci (lobectomy plus topectomy, n 8; two or more topectomies, n 11) with Engel scale outcome Grades 1 (32%, n 6), 2 (47%, n 9), 3 (21%, n 4); and 4 (0%). In contrast, outcome grades for single focus resection patients were Grades 1 (67%, n 19), 2 (11%, n 3), 3 (11%, n 3), and 4 (11%, n 3). For combined Engel Grades 1 and 2 in both groups, there were improvements in activities of daily living, school performance, and subjective assessment of the care team. CONCLUSION: Although seizure elimination was twice as likely in monofocal resection patients versus multifocal patients (Engel Grade 1, 67 versus 32%), we found that seizure control outcomes were comparable between these two groups when Engel Grade 1 and 2 results were combined (78 versus 80%). These observations suggest that, if seizure reduction (as opposed to elimination) can improve development/function in a child, then resection of multiple seizure foci may be as reasonable an approach as monofocal resection.

865 Transsphenoidal Surgery in the Treatment of Pediatric Craniopharyngiomas

Daniel M.S. Prevedello, M.D., Jay Jagannathan, M.D., John A. Jane, Jr., BA, M.D., Edward R. Laws, Jr., M.D. INTRODUCTION: Craniopharyngiomas are the most common sellar/parasellar tumors in the pediatric population. The transsphenoidal resection of pediatric craniopharyngiomas is controversial. METHODS: A neuropathology database was reviewed from 1992 to 2005; 21 pediatric craniopharyngioma patients (age 18 yr) were identified. Clinical records and imaging were reviewed. The mean age was 11.1 years (range, 2.517.5 yr) and the mean follow-up period was 34.1 months. Most patients (n 19, 90.5%) had sellar and extrasellar disease. Tumor size ranged from 13 to 52 mm. Ten patients had undergone previous treatment, of whom all had undergone at least one craniotomy. Common preoperative findings included endocrinopathy (90.5%), growth delay (57%), headache (71.4%), visual field

NEUROSURGERY

VOLUME 59 | NUMBER 2 | AUGUST 2006 | 475

ABSTRACTS

OF

OPEN PAPERS

impairment (57.1%), optic atrophy (28.6%), diabetes insipidus (61%), and hydrocephalus (14.2%). RESULTS: Gross total excision was accomplished in 76.2% and radical subtotal excision in 9.5% of the patients. A fat graft was required in 20 patients (95.2%) to repair the cranial base. Visual improvement occurred in 23.1% and normalization in 46.2%. Optic atrophy predicted failure to normalize vision (P 0.01). Vision was transiently worsened in one patient and permanently affected in another (right temporal visual field defect). Postoperative cerebral spinal fluid leak occurred in two patients (9.5%), requiring repeat surgery for repair. There were no cases of meningitis. Four patients (44%) had transient and four (44%) new permanent diabetes insipidus. Three (50%) developed new panhypopituitarism. One patient, who had a previous history of postcraniotomy stroke, had another brain infarct 20 days postoperatively and died. Three patients (14.3%) developed recurrence at a mean of 25.1 months. One patient has been observed, one underwent gamma knife radiosurgery, and one underwent a second transsphenoidal operation. At the last follow-up examination, 71.4% of patients were living and well, 23.8% were living with partial visual deficit, and one patient (4.7%) died of disease progression. CONCLUSION: The transsphenoidal approach provides a reasonable alternative to craniotomy for the treatment of selected pediatric craniopharyngioma patients.

CONCLUSION: Effective clinical translation of central nervous system gene therapy requires the development of novel delivery approaches that have not been part of traditional neurosurgical practice. Several novel methods, which were distinct from our previous human experience with focal gene therapy, were required here for more global gene delivery. These results indicate that relatively accurate infusion to multiple sites simultaneously can be achieved with minimal cerebrospainl fluid loss or brain shift and without significant surgical complications.

867 Restoration of Impaired Neurodevelopment after Systemic Prenatal Brain Injury in Rats
Shenandoah Robinson, M.D. INTRODUCTION: Systemic perinatal insults cause cerebral palsy and epilepsy in children born preterm. We propose that impaired neural development from prenatal insults includes -aminobutyric acid (GABA)-ergic neuronal loss and is partially reversible using neonatal neuroprotective agents. METHODS: In rats, transient uterine artery occlusion was performed on embryonic Day 18 for 45 or 60 minutes to mimic preterm human insults. Sham-controls had surgery without arterial occlusion. Pups were born at term. Motor tests were performed in neonates and adults. Pentylenetetrazol (PTZ), a GABA-ergic antagonist; NM.D.A, a glutamate agonist; and pilocarpine, a muscarinic agonist, were used to lower the seizure threshold in adult rats. Latency to each of three seizure grades was recorded. Tissue was collected for in vitro, anatomic, and biochemical assays. Immunolabeled cells were counted on coronal sections in a blinded manner. Erythropoietin (2000 U/kg) was administered intraperitoneal on postnatal Days 1 to 5, with saline controls. Comparisons were made using two-tailed t or 2 tests, with P values less than 0.05 considered significant. RESULTS: After a prenatal insult, rat pups and adults showed impaired motor skills compared with sham-controls (P 0.02). PTZ lowered the seizure threshold in insult rats, whereas other nonGABAergic convulsants did not. Lower PTZ doses were required to induce all seizure grades in postinsult rats, compared with sham-controls (P 0.03). In adult postinsult rats, GABA-ergic subpopulation neuron counts including neuropeptide Y and parvalbumin were significantly decreased in multiple cortical areas (P 0.03). Erythropoietin partially reversed neonatal brain damage and raised the seizure threshold in mature insult rats, compared with saline-treated controls. CONCLUSION: These results suggest impaired cortical development after perinatal injury in premature infants is owing, in part, to cortical GABA-ergic neuronal loss, and that this deficit is partially restored by neuroprotective agent administered in the neonatal period. These results demonstrate sustained erythropoietin-induced improvement in adults after a prenatal insult, a novel therapeutic strategy for perinatal brain injury.

866 Surgical Targeting and Focal Implantation of Gene Therapy for Global Neurological Disease: Operative Technique and Nuances
Justin F. Fraser, M.D., Mark M. Souweidane, M.D., Michael G. Kaplitt, M.D., Ph.D., Dimitris Placantonakis, M.D., Linda Heier, M.D., Stephen Kaminsky, Ph.D., Lisa Arkin, Dolan Sondhi, Ph.D., Neil Hackett, Ph.D., Barry Kosofsky, M.D., Ronald Crystal, M.D. INTRODUCTION: Gene therapy for neurological diseases is currently under transition from bench to bedside. Only one previous human trial has attempted gene therapy for a global neurogenetic disorder. The requirements for global delivery present unique neurosurgical challenges, which differ from those seen in previous singlesite infusion studies. METHODS: Nine patients with Battens disease underwent focal infusion of an AAV2 vector containing a normal copy of the ceroidlipofuscinosis, neuronal 2 gene through 12 injections (two/injection site) in the cerebral cortex. Operative technique was studied to assess efficiency. Patients were studied with postoperative magnetic resonance imaging scans to evaluate vector delivery. RESULTS: The degree of cerebral atrophy was substantial compared with normal patients at this age. Frameless stereotaxy was used for trajectory planning and burr hole placement to avoid delivery into the subarachnoid space. This accurately predicted gyral locations in nearly all burr holes. Twenty-gauge spinal needles used as guide tubes for borosilicate infusion catheters were fixed along trajectories using the Sugita headframe, with the needle tip just deep to the pia. This permitted accurate placement of the infusion catheter at the two depths along each tract. Burr holes were filled with fibrin glue after fixation of the guide needle, to minimize cerebrospinal fluid loss. No postoperative hemorrhages were noted. A radiographic correlate of injection was recognized in 70% of sites, though the sensitivity of magnetic resonance imagin scans to detect vector infusion is, as yet, unknown.

868 Pediatric Cerebral Aneurysms: Characteristics, Pathogenesis, Surgical and Endovascular Management, and Outcome
Paul Kim, M.D., Michael Raber, B.S., Alexander K. Powers, M.D., Pearse Morris, M.D., Steven S. Glazier, M.D. INTRODUCTION: Although angiographic vasospasm has been demonstrated in children with aneurysmal subarachnoid hemor-

476 | VOLUME 59 | NUMBER 2 | AUGUST 2006

www.neurosurgery-online.com

ABSTRACTS

OF

OPEN PAPERS

rhage, it is generally felt that vasospasm is well tolerated without associated neurological deterioration. We present our series of pediatric cerebral aneurysms treated with surgical clipping and endovascular techniques. We also describe two cases of severe, medically refractory clinical vasospasm, which were successfully managed endovascularly. Pathological specimen were reviewed for further elucidation regarding the histopathology of pediatric aneurysm formation. METHODS: From 1996 to 2004, 14 children (younger than 17 yr) with cerebral aneurysms were evaluated at Wake Forest Baptist Hospital. Medical records and radiographic studies were reviewed to determine patient demographics, clinical presentation, radiographic findings, treatment, and outcome. RESULTS: Ten patients underwent craniotomy for aneurysm clipping. Seven of these presented with subarachnoid hemorrhage. On presentation, five were Hunt and Hess Grade III, one was Grade II, and one was Grade V. Two patients with ruptured anterior communicating artery aneurysms exhibited worsening hemiparesis and mental status with severe angiographic vasospasm, which resolved after several endovascular treatments with papaverine and nicardipine. Two patients with basilar artery dissecting aneurysms underwent endovascular management with successful outcomes. All patients had excellent outcomes (Glasgow Outcome Scale 5), except for one who died after surgery (Hunt and Hess Grade V with complex middle cerebral artery aneurysm). In one pathological specimen, a segment of the parent vessel adjacent to the aneurysm neck exhibited fragmentation of the internal elastic lamina and muscularis layers, supporting previous reports. CONCLUSION: In contrast to previous reported series of pediatric aneurysms, we found a relatively high incidence of symptomatic vasospasm with neurological deterioration that was successfully treated with interventional management.

Improvement (excellent and partial) was 83.8% in endoscopic procedures versus 72.7% in the open surgical group. The duration of hospitalization was 3. 6 versus 8.9 days, the rate of complications was 7. 9 versus 29.1%, and the rate of recurrence requiring surgery was 8.2 versus 0%, respectively. CONCLUSION: Endoscopic Chiari decompression significantly decreased the chance of complications, shorten hospitalization, and improve postoperative recovery when compared with the conventional open procedure. Acknowledging of the limit of retrospective, nonblinded, and nonrandominzed study, we suggest further evaluation of endoscopic bony Chiari decompression.

870 Multiloculated Hydrocephalus: A Study of 24 Patients Operated by Endoscopic Cyst Fenestration

Nasser M.F. El-Ghandour, M.D. INTRODUCTION: The treatment of multiloculated hydrocephalus is a difficult problem in pediatric neurosurgery. Definitive treatment is surgical, yet the approach remains controversial. We have, therefore, reviewed our results with endoscopic cyst fenestration (ECF) in the management of this disease. METHODS: We present the largest series to date of multiloculated hydrocephalus operated by endoscopy (24 patients). Uniloculated hydrocephalus is not included in this study because it is a different entity that would be better studied separately. Surgical treatment included ECF (24 patients), endoscopic revision of malfunctioning preexisting shunt (6 patients), placement of new shunt (15 patients), and third ventriculostomy (3 patients). RESULTS: The group included 10 males and 14 females with a mean age of 12.5 months. Neonatal meningitis was the most common cause (9 patients), followed by intraventricular hemorrhage (6 patients), postoperative gliosis (6 patients), and multiple neuroepithelial cysts (3 patients). Multiplanar magnetic resonance imaging scans make early diagnosis and are indicated if the computed tomographic scan shows disproportionate hydrocephalus. ECF was easily performed in all cases with devascularization of cyst wall by coagulation to prevent recurrence. The results are encouraging, with improvement of hydrocephalus in 18 patients (75%). The need for shunting was avoided in three patients (12.5%). Endoscopy reduced the shunt revision rate from 2.9 per year before fenestration to 0.2 per year after fenestration. During the mean follow-up period (30 months), repeat ECF was necessary in eight patients (33.3%). Six out of these eight patients (75%) were already shunted before endoscopy. Endoscopic complications were minimal (two cerebrospinal fluid leakage, two minor arterial bleeding) and no mortalities (0%). CONCLUSION: ECF is recommended as the procedure of choice in the treatment of multiloculated hydrocephalus because it is effective, simple, minimally invasive, and associated with low morbidity and mortality rates.

869 Recovery, Improvement, and Complications after Endoscopic versus Conventional Open Chiari Decompression
Xiao Di, M.D., Ph.D., Mahamoud G. Ammar, M.D., Mark G. Luciano, M.D. INTRODUCTION: Endoscopic chiari decompression allows bony decompression through a 2-cm incision. The small incision and decompression have a potential of faster, limited, and less complicated recovery. This study compares the recovery rates from preoperative symptoms, duration of hospital stay, postoperative complications, and recurrence after endoscopic versus nonendoscopic open procedure. METHODS: We retrospectively reviewed the records of all patients with Chiari Type I malformation who had undergone initial suboccipital craniectomy and upper cervical (C1, C2) laminectomies for Chiari decompression between January 1995 and December 2005. Patients were allocated to a nonendoscopic group whose procedure was performed with the assistance of surgical loupes and a microscope and to an endoscopic group whose procedure was operated directly under 0- or 30-degree endoscopes. Improvement (excellent, partial, no change, and worse) after surgery, hospital stay, postoperative complications, and preoperative symptomatic recurrence were analyzed via the 2 and Kaplan Meier tests. RESULTS: There were 148 patients who underwent Chiari decompression from January 1995 to December 2005. Among these, 38 patients (25.7%) underwent endoscopic procedure in the past 2 years.

871 Shunting versus Endoscopic Third Ventriculostomy: Long-term Cognitive Outcome

Maureen Lacy, Ph.D., Benjamin Pyykkonen, Dawn Mottlow, M.S.N., R.N., Tien Do, M.A., Scott Hunter, Ph.D., David M. Frim, M.D. INTRODUCTION: Neurocognitive deficits continue to be documented in individuals with hydrocephalus. Previous research indi-

NEUROSURGERY

VOLUME 59 | NUMBER 2 | AUGUST 2006 | 477

ABSTRACTS

OF

OPEN PAPERS

cates that both children and adults experiencing hydrocephalus display deficits in memory function, language fluency, nonverbal skills, and strategic planning. However, patients who undergo early surgical intervention often show improvements in memory function and language fluency, yet frontal lobe dysfunction often persists. Scant research examines the impact of surgical procedure on long-term cognitive outcome. The current study examines neurocognitive outcome related to different treatment interventions for hydrocephalus. METHODS: Thirty-two adults who underwent surgical intervention for hydrocephalus completed a neuropsychological battery. Twenty-four patients with a programmable valve shunting system were compared with eight individuals with a nonshunting obstructive bypass system (endoscopic third ventriculocisternostomy, ETV) across the test battery. RESULTS: Inspection of data revealed that scores for both groups were consistently one standard deviation below normative means, despite normal estimates of premorbid intellect. Independent sample t tests revealed significant group differences on the Mini-Mental State Examination (P 0.01) and several measures of executive functioning (P 0.03). Specifically, the ETV patients performed at least one standard deviation below the shunted patients on measures of planning and inhibition. In addition, a trend towards better performance on memory measures was noted within the shunted group when compared with ETV patients. CONCLUSION: Individuals who underwent shunting within the first year of life and individuals who underwent ETV more than 1 year ago continue to display mild cognitive inefficiencies in adulthood, regardless of age or emotional status. Inspection of the data revealed significant memory retrieval and speeded mental processing deficits, along with subtle executive inefficiencies. There was a significant difference between the groups on a global measure of cognition, along with several executive tasks. We theorize that the enlarged ventricles after ETV may disrupt frontal networks, rendering them at a higher risk for subtle cognitive dysfunction than shunted patients.

intra-, and postoperative care with the presence or absence of shunt infection after 6 months as the primary outcome measure. RESULTS: To date, 44 patients have been enrolled for a total of 47 shunt procedures. The study group numbers 24 procedures and the control group 23. No shunt infections have occurred in the study group, whereas four shunt infections have been diagnosed and treated in the control group. Right-tailed Fisher exact analysis of this distribution supports statistical significance (P 0.050) with a relative risk reduction of at least 18.7% (95% confidence interval, 0.187infinity). CONCLUSION: Preliminary data analysis suggests that the use of antimicrobial suture for shunt surgery wound closure is associated with a lower incidence of postoperative shunt infections.

873 Prolonged Exposure to Antibiotic-impregnated Shunt Catheters does not Increase the Incidence of Late Shunt Infections
Daniel M. Sciubba, M.D., Matthew J. McGirt, M.D., Graeme F. Woodworth, B.S., Benjamin S. Carson, M.D., George I. Jallo, M.D., F.A.C.S. INTRODUCTION: Antibiotic-impregnated shunt (AIS) systems have been designed to prevent the colonization of shunt components by skin flora that occurs at surgery. Although such systems may decrease the incidence of early shunt infections (those occurring within 6 months of shunt placement), it is unclear if such exposure to prolonged antibiotics leads to an increased incidence or virulence of late shunt infections (those occurring longer than 6 months after shunt placement). In this study, the authors evaluate the incidence of late shunt infection after the introduction of an AIS system in a pediatric hydrocephalus population. METHODS: We prospectively reviewed all pediatric patients undergoing antibiotic-impregnated cerebrospinal fluid shunt insertion or shunt revision operations at our institution for the 33-month period between October 1, 2002 and June 31, 2005. All shunt-related complications, including shunt infection, were evaluated in those patients with follow-up periods greater than 6 months. RESULTS: A total of 153 pediatric patients (age range, 121 yr) underwent 262 shunting procedures involving use of antibioticimpregnated catheters. All patients were followed for longer than 6 months with a mean follow-up period of 15.7 months (range, 740 mo). Ten patients (3.82%) experienced an early shunt infection within the 6-month follow-up period. No patients experienced a late shunt infection. CONCLUSION: AIS catheters do not lead to a significantly increased incidence of late cerebrospinal fluid shunt infection in children with hydrocephalus compared with historic controls.

872 Antimicrobial Suture Use Associated with a Decreased Incidence of Cerebrospinal Fluid Shunt Infections
Jody Leonardo, M.D., Curtis J. Rozzelle, M.D. INTRODUCTION: Implantation of cerebrospinal fluid shunting devices is associated with a 5 to 10% risk of infection, as cited in the contemporary pediatric neurosurgical literature. Shunt infections typically require complete removal of the device and prolonged antibiotic treatment followed by shunt replacement. Moreover, shunt infections are commonly associated with prolonged hospital stays, potential comorbidity, and the increased risk of neurological compromise owing to ventriculitis or other shunt-related complications. METHODS: A prospective, randomized, double-blinded study is currently underway at our institution. Newly diagnosed and established hydrocephalus patients are randomized at the time of shunt surgery into study and control populations with wound closures performed using antimicrobial absorbable suture (Vicryl-Plus, Ethicon, Inc., Somerville, NJ) or standard absorbable suture (Vicryl, Ethicon, Inc.), respectively. Randomization is categorized so that factors known to influence infection risk are equally represented in both groups. Additional data recorded pertains to demographics, surgical history, infection history, body habitus, and antibiotic use to facilitate post hoc analysis. Study and control patients receive identical pre-,

874 Noninvasive Measurement of Intracranial Pressure and Cerebral Blood Flow in Patients with Hydrocephalus: A Clinical Predictive Tool
Roberta P. Glick, M.D., Terry Lichtor, M.D., Ph.D., Osbert Egibor, M.D., Sang H. Lee, Ph.D., Josh Niebrugge, M.D., Noam Alperin, Ph.D. INTRODUCTION: The decision for surgical intervention in hydrocephalic patients with symptoms suggesting raised intracranial pressure (ICP) is challenging because ventricle size often lacks the speci-

478 | VOLUME 59 | NUMBER 2 | AUGUST 2006

www.neurosurgery-online.com

ABSTRACTS

OF

OPEN PAPERS

ficity to predict abnormal ICP. An early assessment of the potential clinical utility of a noninvasive magnetic resonance imaging (MRI)based measurement of intracranial pressure (MR-ICP) in symptomatic hydrocephalic patients is reported. METHODS: Twenty-seven symptomatic hydrocephalic patients, (17 shunted and nine non-shunted) underwent brain MRI studies, which included measurements of cerebrospinal fluid and cerebral blood flows to and from the cranial vault from which measurements of ICP and cerebral blood flow were derived using a previously described algorithm. The predictive values of the MR-ICP measurement were determined based on whether or not the patient underwent a surgical treatment of a shunt placement or shunt revision within a 3-month period following the MRI study. RESULTS: MR-ICP values in these patients spanned a much wider range than in healthy control subjects. Yet, the majority of the patients (20 out of 26) had MR-ICP values within the normal range. Similarly, TCBF in these patients did not follow the normal distribution, but spanned a much wider range. CONCLUSION: The short-term follow-up of patients who had normal MR-ICP measurement reveals that only one of the 20 required surgery. Consequently, the MR-ICP measurement has a strong negative predictive value (95% for all patients and 100% for patients without a shunt).

patients. With aggressive management, the mortality can be brought to zero and the morbidity minimized, especially in children.

876 Recurrence of Synostosis after Surgical Repair of Craniosynostosis

Kimberly A. Foster, B.A., McKay McKinnon, M.D., David M. Frim, M.D. INTRODUCTION: Incidence of resynostosis in patients having undergone surgical release of a synostotic suture is not well reported. This study examines cases of non-syndromic and syndomic craniosynostosis having undergone surgical repair and establishes the rate of reoperation for synostosis in the series. METHODS: Charts were retrieved from 119 consecutive patients treated for craniosynostosis at our institution (62% male; 11% treated for craniofacial dysostosis; Apert syndrome, n 2; Crouzon syndrome, n 4; Saethre-Chotzen, n 5; other, n 2). RESULTS: Eight (6.7%) patients underwent operation for resynostosis (nonsyndromic, 6 out of 106, 5.7%; syndromic, two out of 13, 15.4%). Seventy-nine (66.4%) patients underwent primary surgery at younger than 1 year of age. Analysis by age at primary operation yielded significant resynostosis rates (P 0.02) when patients younger than 1 year of age (n 2, 2.5%) are compared with those older than 1 year of age (n 6, 15%). Further stratifications of age at initial reoperation did not yield significance for resynostosis. Cases with documented raised intracranial pressure preoperatively (n 9, 7.6% of total population) are noted to have an increased rate of resynostosis (n 4, 44.4%, P 0.001). A trend of increasing mean length of hospital stay, estimated blood loss, and operative time in the patients who eventually resynostosed is observed, but the data were not significant. CONCLUSION: Resynostosis rates were higher in syndromic children than in nonsyndromic cases in which a single suture was involved. Analysis of age at primary operation shows an increase in resynostosis if primary operation occurs after the age of 1 year. In addition, evidence of raised intracranial pressure at primary operation may predispose to recurrence of craniosynostosis.

875 Pediatric Infratentorial Subdural Empyemas: A Series of 14 Patients

Paritosh P. Pandey, M.B.B.S., M.C.H. INTRODUCTION: Infratentorial empyemas are rare lesions, forming only 0.6% of all cases of intracranial suppurative disorders. Posterior fossa empyemas are associated with high morbidity and mortality despite prompt and aggressive treatment. METHODS: A series of 14 children (age 18 yr ) over a period of 10 years (19952005) were analyzed retrospectively. RESULTS: This condition was predominantly found in males (64%) and in the summer months. The source of infection was middle ear infection in 92.9%. Clinical features were a combination of headache, fever, vomiting, and meningism in a setting of ear discharge. Cerebellar signs were found in only 21% of patients; 85.7% of patients were in altered sensorium with Glasgow Coma Scale scores between 11 and 14. In 79.6% of patients, pus collection was seen over the cerebellar convexity. Other sites were tentorial (28.6%) and the cerebellopontine Angle (21.4%). All patients were started on antibiotics. All patients were operated on (burr holes in 21%, craniectomy in 79%). Four patients required repeat surgery for residual empyemas. Hydrocephalus was seen in 92.9% of the patients. Five patients needed external ventricular drainage during surgery or postoperatively and two required shunt for persistent ventriculomegaly. The pus culture positivity rate was 71.4%, and 21% of patients had polymicrobial infection. Three patients developed minor postoperative complications. There was no mortality in the series. Follow-up data was available for nine out of 14 patients. Glasgow Outcome Scale scores at the time of follow-up were good, with scores of 5 or 4 in all patients. CONCLUSION: Posterior fossa empyemas present with a nonspecific constellation of symptoms. Cerebellar signs are seen in only a minority. Surgery and antibiotics are the mainstays of treatment. Hydrocephalus may be managed with external ventricular drainage and a permanent shunt is needed in only a small percentage of

877 Psychobehavioral Effects of Chronic Subthalamic Stimulation and the Topography of Subthalamic Nucleus
Sheng-Tzung Tsai, M.D., Shin-Yuan Chen, M.D. INTRODUCTION: Psychobehavioral effects of chronic subthalamic stimulation (STN-DBS) in Parkinsons disease (PD) are variable. Whether these side effects resulted from target per se or current diffusion into neighboring structures was uncertain. The relationship between the clinical outcome and the active electrode contact was analyzed and was compared between the patients with and without psychobehavioral consequence. METHODS: Thirty-eight consecutive PD patients who underwent bilateral STN-DBS were enrolled in this retrospective cohort study. At the time of follow-up, they were divided into two groups for comparison: Group A (with psychobehavioral side effect) and Group B (without psychobehavioral side effect). The position of the active contact of the electrode was defined with postoperative magnetic resonance

NEUROSURGERY

VOLUME 59 | NUMBER 2 | AUGUST 2006 | 479

ABSTRACTS

OF

OPEN PAPERS

imaging scans. The active contact coordinates and the clinical outcomes were compared between the two groups. RESULTS: Among these 38 PD who underwent STN-DBS, eight patients who had psychobehavioral side effects were assigned to Group A; the other 30 patients were assigned to Group B. In Groups A and B, the mean follow-up period was 13.9 and 7.1 months, respectiveley, and the UPDRS motor score was improved by 53.4 and 45.2%, respectively (P 0.24), and the LEDD was decreased by 68.4 and 46.4%, respectively (P 0.16). The mean coordinates of the active contact in both groups were x 10.1 and 10.5 mm, y 2.8 and 3.9 mm, and z 6.3 and 6.2 mm, respectively. A significant difference was observed on the y axis (P 0.01). When we compared the coordinates between the groups side by side, a significant difference was observed on the y axis of left side (P 0.007; odds ratio, 12.0). CONCLUSION: The psychobehavioral effects of chronic STN-DBS were significant related to an anteriorly located electrode in the left STN, despite a prominent improvement in the motor symptoms. The posterior lateral portion of the STN will be an optimal area to place the electrode without causing psychobehavioral side effects during chronic stimulation.

dimensions. A reduction in brain activation volume was observed only in investigational patients. CONCLUSION: CS improves hand/arm function over intensive rehabilitation alone; this correlates with consolidation of brain activation on functional magnetic resonance imaging scans. CS may also improve neurocognitive function after stroke.

879 Therapeutic Cloning in Mice

Viviane S. Tabar, M.D., Teru Wakayama, Ph.D., Georgia Panagiotakos, B.S., Bill Chan, B.A., Mark Tomishima, Ph.D., Lorenz Studer, M.D. INTRODUCTION: Despite recent concerns about claims of human nuclear transfer in humans, cloning of somatic cells in vertebrates is well-described and reproducible. METHODS: We obtained tail cells from a group of five mice and transferred the nuclei by microinjection into enucleated oocytes obtained from donor mice. The oocytes developed into blastocysts and embryonic stem (ES) cell lines were derived. The ES lines, now carrying the genotype of the tail cell donor, were subjected to a neural induction protocol and differentiated into dopamine neurons following our previously described methods. The tail donor mice were rendered Parkinsonian by intrastriatal injection of 6-hydroxydopamine and their behavior abnormalities were subsequently quantified. The dopamine neurons obtained from the tails were injected in the striatum of the corresponding lesioned donor animal and the rotational behavior measured over 3 months. RESULTS: Our data demonstrates graft survival, maintenance of dopaminergic phenotype, and behavioral improvement of the Parkinsonian animals. The efficiency of generation of ES lines from cloned blastocysts will be discussed. CONCLUSION: This is the first demonstration that cloning can be used therapeutically. We were able to derive for each Parkinsonian animal its own autologous dopamine neurons starting with a tail biopsy. The nuclei of the tail cells were transferred into enucleated oocytes and ES lines were successfully generated. The ES lines offer an enormous potential for differentiation into a multitude of lineages or phenotypes, including cardiac cells, muscle cells, vascular epithelium, cartilage, bone, or neurons. Thus the promise of this technology is enormous.

878 Cortical Stimulation for Motor Recovery after Stroke: Impact on Neuropsychological Performance and Functional Imaging
Robert M. Levy, M.D., Amity Ruth, Ph.D., Mark E. Huang, M.D., Richard L. Harvey, M.D., Sean Ruland, D.O., Rima Dafer, M.D., David Lowry, M.D., Martin E. Weinand, M.D. INTRODUCTION: Persistent upper extremity weakness and cognitive deficits commonly result from stroke. We tested the hypotheses that cortical stimulation (CS) combined with intense rehabilitation therapy could stimulate functionally significant neuroplasticity evident on functional imaging, enhance motor recovery, and improve deficits in neurocognitive function after stroke. METHODS: Two randomized prospective studies were conducted at eight clinical sites. Functional magnetic resonance imaging scans both before and after therapy was used to define the cortical hand region. Thirty-two patients with hand/arm weakness from ischemic stroke of 4 or more months earlier were randomized to an investigational epidural grid electrode over hand motor cortex and pulse generator that delivered CS during rehabilitation (investigational group) or rehabilitation alone (control group). Motor function was assessed using the Upper Extremity Fugl-Meyer (UEFM) scale. A neuropsychological test battery was administered before and after therapy. RESULTS: The investigational group showed greater improvements in motor function compared with controls at 4 weeks (UEFM, 6.4 versus 1.9 points; P 0.01) and 12 weeks (UEFM, 7.2 versus 2.4 points; P 0.01) after completion of therapy. More investigational patients had clinically meaningful motor function improvements (4 wk: 71 versus 31%, P 0.01; 12 wk: 81 versus 38%, P 0.01). Investigational patients with left-sided stroke demonstrated more language improvement than controls, as measured by the Wechsler Abbreviated Scale of Intelligence vocabulary t-score (1.3 versus -3.8 points; P 0.05). A trend for greater gains in confrontation naming (in left-sided stroke patients) and on visuospatial abstraction (in right-sided stroke subjects) was also observed for investigational patients. Activation site variability was substantial (12, 23, and 11 mm in x, y, and z directions, respectively), exceeding electrode

880 Pediatric Language Mapping: Sensitivity of Neurostimulation and Wada Testing in Epilepsy Surgery
Howard L. Weiner, M.D., Catherine Schevon, M.D., Ph.D., Chad Carlson, M.D., Werner Doyle, M.D., Daniel Miles, M.D., Josiane LaJoie, M.D., Ruben Kuzniecky, M.D., Orrin Devinsky, M.D. INTRODUCTION: Functional mapping of eloquent cortex with electrical neurostimulation was utilized both intra- and extraoperatively to tailor resections. In pediatric patients, functional mapping studies frequently fail to localize language, and Wada testing has also been reported to be less sensitive in children. METHODS: Thirty children (4.714.9 yr) and 18 adult controls (1859 yr) who underwent extraoperative language mapping via implanted subdural electrodes at the New York University Comprehensive Epilepsy Center were included in the study. Ten children and 14 adults underwent preoperative Wada testing. Success of the procedures was defined as the identification of at least one language site by

480 | VOLUME 59 | NUMBER 2 | AUGUST 2006

www.neurosurgery-online.com

ABSTRACTS

OF

OPEN PAPERS

neurostimulation mapping and determination of hemispheric language dominance on the Wada test. RESULTS: In children under the age of 10.2 years, cortical stimulation failed to identify language cortex at a higher rate than was seen in children over the age of 10.2 years and in adults (P 0.05). This threshold, demonstrated by survival and x2 analysis, was sharply defined in our data set. Additionally, Wada testing was more likely to be successful than extraoperative mapping in this younger age group (P 0.05). CONCLUSION: Analysis of our series demonstrated that language cortex was less likely to be identified in children younger than 10 years of age, suggesting that alternatives to the currently used methods of cortical electrical stimulation, particularly the use of preoperative language lateralization, may be required in this age group.

for brain-computer interfaces and intracortical activity, which may be useful in a variety of clinical settings (e.g., epilepsy monitoring).

882 Tailored Temporal Lobectomy for Medically Intractable Epilepsy: Long-term Outcomes in a Series of 140 Consecutive Patients
Richard W. Byrne, M.D., Kirk W. Jobe, M.D., Nimesh H. Patel, M.D., Michael C. Smith, M.D., Andres M. Kanner, M.D., Matthew Morrin INTRODUCTION: Tailored temporal lobectomy utilizes electrocochleography, neuropsychological, and other data to limit the amount of resection performed in temporal lobe epilepsy cases. Because less temporal lobe tissue is often removed than in a standard lobectomy, concern remains that long-term seizure outcomes may be inferior. METHODS: We analyzed our prospectively maintained database for a review of Engels Class outcomes in a series of patients undergoing temporal lobe epilepsy surgery during a 6-year period. Standard demographic data, epilepsy risk factors, side of surgery, extent of resection on the lateral cortex, extent of hippocampal resection, and pathology were evaluated as independent predictors of seizure outcome. RESULTS: One hundred and forty consecutive patients had at least 2-year follow-up and met the criteria for the study. Eighty four patients had mesial temporal sclerosis, and 29 patients had low-grade glioma. Seventy-nine percent of patients were Engels Class I (a-d) at last follow-up. The complication rate was 2.8% (dysphasia, 2; wound infection, 2). Abnormal magnetic resonance imagining findings of mesial temporal sclerosis or tumor was the only factor significantly correlated with Engel Class I outcome (P 0.01). Greater extent of lateral resection (P 0.1) and fewer preoperative seizures both showed a trend towards better seizure outcome that did not reach statistical significance (P 0.1). Extent of hippocampal resection did not correlate with seizure outcome (P 1.0). In a subclass of 39 patients with pre- and postoperative Wechsler neuropsychological testing, extent of hippocampal resection did not correlate with immediate or delayed memory scores (P 1.0, P 0.4). CONCLUSION: In temporal lobe epilepsy, excellent post surgical outcomes are achievable with very low morbidity using the tailored technique. As in most series, the outcome is influenced by pathology. At a minimum of 2 years follow-up, cases where the extent of resection of the hippocampus was limited to the anterior 2.5 cm had similar outcomes to cases where a full hippocampal resection was performed.

881 Initial Surgical Experience with an Intracortical Microelectrode Array for Brain-computer Interface Applications
Gerhard Friehs, M.D., Richard D. Penn, M.D., Michael C. Park, M.D., Ph.D., Marc Goldman, M.D., Vasilios A. Zerris, M.D., Leigh R. Hochberg, M.D., Ph.D., David Chen, M.D., Jon Mukand, M.D., Ph.D., John D. Donoghue, Ph.D. INTRODUCTION: We report our initial experience implanting a 4 x 4 mm 96-channel intracortical microelectrode array, which is being tested in a pilot safety and feasibility trial for the development of brain-computer interfaces for people with paralysis. METHODS: The BrainGate Neural Interface System includes an implantable sensor (a microelectrode array) with a percutaneous pedestal and external components for signal processing, signal decoding, and external device control. The array consists of 100 1 to 1.5 mm silicon probes, 96 of which are active electrodes. Using a pneumatic inserter, the array is implanted into the precentral knob (arm and/or hand area), as identified by preoperative magnetic resonance imaging scans. The pedestal is secured to the cranium and externalized percutanteously, allowing a cable to connect to external components. After allowing for wound healing (approximately 2 wk), neural recordings are obtained at least weekly. Participants were asked to imagine limb movements and attempts were made to decode the real-time neural activity into a useful control signal for an external device (e.g., a computer cursor). Patients aged 1870 with spinal cord injury, brainstem stroke, or muscular dystrophy with limited use of their arms and/or hands were eligible for our ongoing study. RESULTS: We report on two patients with spinal cord injury who experienced array implantation. Surgical time was less than 3 hours in both cases. Patients were discharged from the hospital after 2 to 3 days. No surgical infections occurred, and there were no unanticipated adverse device effects. Recordings demonstrate the presence of neurons and the patients ability to modulate the recorded activity with movement intention. Recordings began in the second patient after a defect in the pedestal was repaired. The array was removed in Patient 1 at the end of the planned trial period of 1 year. Array removal was straightforward. No grossly notable tissue reaction was noted except for a slight indentation of the cortex. The superficial aspect of the array seemed secured by an arachnoid-like membrane. Postoperative recovery was uneventful. CONCLUSION: Our preliminary experience indicates that a small array of microelectrodes can be successfully implanted and removed from the human motor cortex. This array may provide a useful sensor

883 Lentiviral Delivery of Glial Cell Line-derived Neurotrophic Factor in Aged 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine-treated Rhesus Monkeys
Marina E. Emborg, M.D., Ben Z. Roitberg, M.D., Jeffrey Moirano, B.S., Romaine Zufferey, Ph.D., Allison D. Ebert, Valerie Joers, B.S., James Holden, Ph.D., Alexander K. Converse, Ph.D., James B. Koprich, M.D., Jeffrey H. Kordower, Ph.D., Patrick Aebischer, M.D. INTRODUCTION: Aging and environmental toxins have been identified as risk factors for sporadic Parkinsons disease. In this study, we assess the potential for functional recovery induced by glial cell line-derived neurotrophic factor (GDNF ) in a diseased and aged primate brain.

NEUROSURGERY

VOLUME 59 | NUMBER 2 | AUGUST 2006 | 481

ABSTRACTS

OF

OPEN PAPERS

METHODS: Male rhesus monkeys, aged 24 to 30 years, received a single intracarotid infusion of 1-methyl-4-phenyl-1,2,3,6tetrahydropyridine (MPTP), which resulted in unilateral parkinsonism. It was followed 1 week later by magnetic resonance imaging-guided stereotaxic intrastriatal and intranigral injections of lentiviral vectors encoding for GDNF (lenti-GDNF, n 5) or lacZ (lenti-LacZ, n 4). RESULTS: Lenti-GDNF treated monkeys had a significant improvement in the clinical rating compared with lenti-LacZ starting at 5 weeks after surgery that persisted until necropsy. The fine motor skills on a timed pick-up test slowly improved in the lenti-GDNF treated monkeys while lenti-LacZ animals had extreme difficulties or were unable to complete the task. Positron emission tomography scans performed 12 weeks after surgery (before necropsy) revealed increase fluorodopa uptake in the caudate and putamen ipsilateral to lenti-GDNF treatment compared with lenti-LacZ that correlated with the clinical rating score. GDNF enzyme-linked immunosorbent assay of striatal brain samples confirmed high GDNF expression in lentiGDNF treated monkeys. The high levels were associated with increased F-Dopa uptake and behavioral improvement. Immunohistochemistry revealed: 1) GDNF and LacZ gene expression 3 months after surgery in the target areas; 2) increased dopaminergic markers immunoreactivity (tyrosine hydroxylase and VMAT2) associated with areas of GDNF expression; 3) minimal micro- and astrogliosis as observed with CD68 and glial fibrillary acidic protein specific antibodies. CONCLUSION: Our results indicate that the aged primate brain exposed to a neurotoxic insult is responsive to GDNF neuroprotective trophic stimulation locally delivered by lentiviral vectors.

TDS (P 0.001) (Wilcoxon signed-rank test). For the secondary evaluation period, the responder rate for 56 patients was 36% for CPS, 50% for GTC, and 36% for TDS. The median percentage reduction was CPS 28%, GTC 50%, and TDS 30%. Seizure reduction was significant for CPS (P 0.005), GTC (P 0.02), and TDS (P 0.001). In 65 implanted patients, including 17 device replacements, there were no serious unanticipated device-related adverse events. Responsive neurostimulation was well tolerated. Results are current as of March 10, 2006. CONCLUSION: An investigation of responsive stimulation using the RNS system demonstrated excellent safety and a significant and sustained reduction in CPS, GTC, and TDS events. Preliminary results indicated that the RNS system may provide a safe and effective treatment for adults with intractable partial-onset epilepsy.

885 A Prospective Randomized Double-blind Trial of Bilateral Thalamic Deep Brain Stimulation in Adults with Tourette Syndrome
Robert J. Maciunas, M.D., Brian Maddux, M.D., David E. Riley, M.D., Christina M. Whitney, R.N.C., Michael R. Schoenberg, Ph.D., Paula J. Ogrocki, Ph.D., Jeffrey M. Albert, Ph.D., Deborah J. Gould, M.D. INTRODUCTION: Medically refractory Tourette syndrome (TS) that persists into adulthood is a devastating disease with limited therapeutic options. We conducted a prospective, double-blind crossover trial of bilateral thalamic deep brain stimulation in five adults with TS. METHODS: Patients were screened by a neurologist, psychiatrist, neurosurgeon, and neuropsychologist. Baseline studies included video recording and administration of standard instruments, including Yale Global Tourette Severity Scale (YGTSS), Tourette Syndrome Symptom List (TSSL), Short-Form 36 (SF-36), and a quality of life Visual Analog Scale (VAS). Bilateral thalamic electrodes were implanted at targets suggested in a previously published report. After random double-blind activation of unilateral or bilateral stimulation, subjects were assessed with video recording, YGTSS, and TSSL. Three months after unblinded bilateral stimulator activation, the same studies were repeated, as well as SF-36, quality of life VAS, and neuropsychological measures. RESULTS: In the randomized phase of the trial, a statistically significant (P 0.03, Friedmans exact test) reduction of score on the modified Rush Video Rating Scale was identified in the bilateral on state compared with either unilateral on state or the bilateral off state. Improvement in raw motor and sonic tic counts, as well as the YGTSS and TSSL scores, was also noted. Benefit was persistent at 3 months after conclusion of the double-blind randomized portion of the trial. Quality of life indices were improved. CONCLUSION: By all criteria, as measured by primary and secondary outcome variables, three of five patients (60%) were significantly improved. Bilateral thalamic deep brain stimulation seems to reduce tic frequency and severity in patients with TS.

884 Safety and Preliminary Efficacy of a Responsive Neurostimulator for the Treatment of Intractable Epilepsy in Adults
Robert R. Goodman, M.D., Ph.D., Guy M. McKhann, II, M.D., Dennis Spencer, M.D., Kenneth P. Vives, M.D., Ryder Gwinn, M.D., W. Richard Marsh, M.D., Robert E. Wharen, M.D., Richard S. Zimmerman, M.D., Theodore H. Schwartz, M.D., Joseph R. Smith, M.D., George I. Jallo, M.D. INTRODUCTION: A multicenter feasibility investigation assessed safety and possible efficacy of the cranially based implantable, programmable Responsive Neurostimulator (RNS) system. METHODS: Patients were 18 to 65 years old with intractable partial-onset seizures and localized epileptogenic onset region(s). Patients with more than 12 simple partial (SP) sensory or motor seizures, complex partial seizures (CPS), or generalized tonic-clonic (GTC) seizures during an 84-day baseline period qualified for implant. The RNS was connected to up to 2 leads (subdural and/or depth), which were targeted to the seizure focus. Adverse events were monitored throughout the trial. Efficacy was assessed during 2 time periods: the 84-day period beginning 28 days postimplant (primary) and the most recent 84 days for which a patient could have received therapy (secondary). RESULTS: During the primary evaluation period, the responder rate ( 50% reduction in seizures) in 48 patients (excluding 8 patients blinded off) was 32% for CPS, 63% for GTC, and 27% for total disabling seizures (TDS) (SP motor, CPS, and GTC). The median percentage reduction in seizure frequency was CPS 27%, GTC 59%, and TDS 29%. Seizure reduction was significant for CPS (P 0.05) and

886 Late Seizures in Patients Initially Seizure-free after Epilepsy Surgery

Theodore H. Schwartz, M.D., William E. Bingaman, M.D., Lara Jeha, M.D., Adriana Tanner, M.D., Michael Sperling, M.D. INTRODUCTION: Surgery for medically intractable epilepsy is currently the most effective means of achieving seizure control. Al-

482 | VOLUME 59 | NUMBER 2 | AUGUST 2006

www.neurosurgery-online.com

ABSTRACTS

OF

OPEN PAPERS

though there are relatively few long-term outcome studies, evidence is mounting that the possibility of late seizure recurrence exists even after an early seizure-free period. No published reports document the rate and predictors of late recurrence in a large series of patients undergoing surgery since the advent of magnetic resonace imaging (MRI) scanning. METHODS: We retrospectively queried the databases of two epilepsy surgery centers. Patients eligible for study had preoperative MRI scans, were seizure free for 1 year after surgery, and had a minimum follow-up period of 3 years. Patients with tumors or vascular lesions were excluded. We performed log-rank comparison of Kaplan-Meier product limit estimates for categorical variables and used a Cox proportional hazards model for continuous variables. Variables that were significant (P 0.05) on a univariate screen were entered into a multivariate forward stepwise Cox regression. RESULTS: The study included 285 patients, 254 with medial temporal lobe, and 31 with neocortical epilepsy. The probability of having a single seizure after being seizure-free for 1 year was 18.3% at 5 years and 32.7% at 10 years. However, only 13% were not seizure-free at the last follow-up. Predictors of late recurrences on both uni- and multivariate analysis were the presence of preoperative generalized tonic seizures in patients with neocortical epilepsy and late age at surgery in patients with medial temporal lobe. MRI scan results and location of surgery were not predictive. CONCLUSION: Although the risk of at least one recurrent seizure after initially successful epilepsy surgery is relatively high, the rate of recurrent intractability is low. The finding that late age at surgery and presence of preoperative generalized tonic seizures are predictors of late recurrence indicates the importance of patient selection and early surgery for persistent seizure control.

RESULTS: Our data demonstrate that one month after cell transplantation, the MGE-grafted animals significantly improved their motor behavioral deficits compared with the fibroblast and vehicle control groups, as assessed using the rotarod (P 0.05) and the elevated body swing tests (P 0.05). Immunocytochemical analysis of the graft demonstrated a 16.4% survival rate. The transplanted MGE cells expressed NeuN and TuJ1 neuronal markers and the synaptic marker synaptophysin indicating innervation of the host cells. In addition there was a fourfold increase in synaptophysin expression in the MGE transplant area (P 0.001) compared with control animals. CONCLUSION: These data suggest that the MGE-derived neuronal precursors may be a promising cell type for cellular therapy in stroke.

888 A Multitarget GABA-ergic Basal Ganglia Transplantation Strategy Enhances Complex Sensorimotor Behavioral Recovery in Hemiparkinsonian Rodents
Karim Mukhida, M.D., Murray Hong, Ph.D., Ivar Mendez, M.D., Ph.D. INTRODUCTION: The current transplantation strategy for Parkinsons disease that places fetal dopaminergic grafts in the striatum (ST) fails to reconstruct basal ganglia circuitry and is limited by the lack of standardized clinical grade cells. It was hypothesized that to produce complete restoration of parkinsonian behavioural deficits, inhibition of the subthalamic nucleus (STN) and substantia nigra (SN) by GABAergic transplants is needed in addition to reconstruction of nigrostriatal circuitry via dopaminergic transplants, and that human neural precursor cells (NPCs) can be used as an alternative to fetal tissue as a standardized source of clinical grade cells for basal ganglia transplants. METHODS: Human fetal telencephalon-derived NPCs were predifferentiated into a GABAergic phenotype in vitro and their electrophysiological characteristics were determined. These cells were transplanted into the STN, SN, or both sites in conjunction with dopaminergic grafts of the ST of rats with unilateral 6-hydroxydopamine lesions. Control animals received dopaminergic grafts alone or in conjunction with undifferentiated NPCs or fetal GABAergic cells derived from the embryonic rat striatal primordia. Complex sensorimotor behavioural recovery was assessed pre- and postlesion and posttransplantation. Ten weeks posttransplantation, graft function and viability was assessed electrophysiologically and immunohistochemically. RESULTS: By 9 weeks posttransplantation, animals that received GABAergic grafts showed significant improvement in lesion-induced behaviours (akinesia, spontaneous forelimb use, and motor function [P 0.05]) compared with control animals. Electrophysiology demonstrated functioning potassium channels in GABAergic NPCs. Confocal microscopy showed that predifferentiated NPCs maintained a GABAergic and neuronal phenotype in vivo. In contrast, undifferentiated cell transplants differentiated exclusively into astrocytes. CONCLUSION: Restoration of dopaminergic activity to the ST in concert with inhibition of the SN and STN by GABAergic grafts promotes a more complete functional recovery of complex sensorimotor behaviors and may be crucial in improving clinical outcomes in patients with Parkinsons disease. Potential clinical application of this strategy may be enhanced by predifferentiated bioreactor-expanded NPCs.

887 Grafts of Neural Precursors Derived from the Basal Forebrain Improve Motor Function in Experimental Stroke
Marcel M. Daadi, Ph.D., Tonya Bliss, Ph.D., Sang-Hyung Lee, Theo D. Palmer, Ph.D., Gary K. Steinberg, M.D. INTRODUCTION: The medial ganglionic eminence (MGE) of the developing basal forebrain is the host of neural precursors with stem cell characteristics. The MGE give rise to specific populations of neuronal precursors that repopulate the developing striatum and cortex. Furthermore, when grafted into the adult rat striatum, the MGE-derived neuronal precursors integrate, mature, and form synapses with host cells. In the present study, we asked the question whether or not MGE-derived neuronal precursors are an efficacious source of neurons for cellular therapy in the rat model of ischemic stroke. METHODS: The MGE cells were derived from transgenic rat embryos carrying the enhanced green fluorescent protein-encoding gene. Adult rats were subjected to one and one-half hour suture occlusion of the middle cerebral artery. Two weeks after the lesion, 2 l of MGE cell suspension at a concentration of 50,000 cell/ l was stereotaxically transplanted into four sites within the lesioned striatum and cortex. As group controls, we used rats subjected to ischemia and transplanted either with fibroblasts or with the vehicle. All animals underwent baseline motor behavioral assessment before and after ischemic lesion and cell transplantation.

NEUROSURGERY

VOLUME 59 | NUMBER 2 | AUGUST 2006 | 483

ABSTRACTS

OF

OPEN PAPERS

889 Continuous Intrathecal Baclofen Infusion in the Treatment of Spastic Cerebral Palsy: A Prospective Multicenter Study
Yves R. Lazorthes, M.D. INTRODUCTION: The purpose was to assess the benefits of Continuous Intrathecal Baclofen Infusion in children with cerebral palsy, not only on spasticity, but also on motor and functional performances. METHODS: Twenty-four patients with severe diffuse spasticity were selected in 11 French centers, using a multidisciplinary approach (age, 68 yr; mean Ashworth score 3 in the lower limbs, failure of oral baclofen). A double-blind screening was performed in all patients with i-Th bolus (starting from 12.5 and increasing to 100 mcg baclofen) until a positive response for lower limbs. Following a succesful trial, patients were considered for implantation (Synchromed system; Medtronic, Inc., Minneapolis, MN). Assessment during a 2-year peroid included spasticity scoring, quantitative functional evaluation (Gross Motor Function Measure scale) and a qualitive questionnaire. RESULTS: Trial procedures resulted in a significant average drop in Ashworth scores in the lower limbs from 3.7 to 1.8 points (average dose, 44 g baclofen). Despite good clinical effects on spasticity, five patients were not implanted. Seventeen patients were followed for 2 years. Effects on lower limbs spasticity remained stable, as was the case in upper limbs (2.4 and 1.7, respective average score) as daily average dose increased from 124 to 185 g. Average GMFM scores remained stable throughout the study, and qualitative evaluations indicated that pain was reduced and ease of mobility and sleep improved. Patients and families expressed a high level of satisfaction Complications occured in 10 patients, mostly in the first months, none leading to any pump explant. CONCLUSION: Results confirms the efficacy of Continuous Intrathecal Baclofen Infusion in reducing severe spasticity in children with cerebral palsy and its clear benefits in patients care and comfort.

RESULTS: We found that high-frequency stimulation in the caudate resulted in a significant enhancement in the rate of learning of specific associations (t test, P 0.001). We then used the electrochemical technique of amperometry and found that highfrequency microstimulation results in a significant release of dopamine within the anterior striatum. These data suggest that the effects of striatal microstimulation are mediated through induced dopamine release. CONCLUSION: Deep brain stimulation is widely used for the treatment of Parkinsons disease, dystonia, tremor, and other disorders. Hence, it is quite feasible to use a similar technique to treat disorders wherein patients exhibit significant learning deficits. The current data suggest that this is feasible. Further studies will be needed to assess the best parameters for stimulation, to ascertain whether cortical stimulation is as effective as striatal stimulation, and to determine whether continuous stimulation is as effective as intermittent stimulation.

891 Dynamic Encoding of Reward Prediction and Movement in the Subthalamic Nucleus of Patients with Parkinsons Disease and Normal Monkey
Felipe A. Jain, B.S., Emad N. Eskandar, M.D. INTRODUCTION: Increasing data indicate that the basal ganglia serve to dynamically and selectively facilitate biologically profitable or rewarding movements. However, the way in which basal ganglia neurons encodes reward information remains opaque. We hypothesized that the subthalamic nucleus (STN) might increase directional selectivity based on the expectation of rewarded versus unrewarded movements. METHODS: Patients with Parkinsons disease undergoing therapeutic deep brain stimulation electrode implantation were asked to participate in the study. During microelectrode recordings, patients performed movements with different expectations of monetary reward. A nonhuman primate performed an identical task but with receipt of a juice reward. RESULTS: We obtained data from 21 neurons in three patients undergoing surgery, and 32 neurons from one monkey. In humans during cue presentation, 52% of neurons showed changes in mean firing based on direction (P 0.01) from unrewarded to rewarded conditions, as did 41% of neurons in the monkey. In humans, the expectation of reward had a significant effect on directional tuning of the population of cells, reversing the preferred direction (P 0.001). In contrast, the normal nonhuman primates did not significantly change directional selectivity as a population. During movement, irrespective of reward status, the majority of neurons exhibited an increase in activity that averaged 180% during the movement period (P 0.001), whereas the normal monkey STN neuronal firing rates tended to decrease (P 0.1) during movement. CONCLUSION: The STN in both humans and normal monkey encodes predictive information about the receipt of reward. In humans, the expectation of reward seems to markedly modify the directional tuning of the population of cells, whereas in the normal state, expectation of reward has a modest effect on the responses. In the parkinsonian state, STN neurons may dynamically inhibit movement by increasing firing, whereas in the normal state, the STN tends to decrease activity, possibly representing movement facilitation.

890 Deep Brain Stimulation for the Enhancement of Learning

Emad N. Eskandar, M.D., Ziv Williams, M.D., Ramin Amirnovin, M.D., Kendall H. Lee, M.D., Charles Blaha, Ph.D. INTRODUCTION: There is increasing evidence that the basal ganglia play a critical role in learning. The neostriatum receives projections from virtually all areas of the cortex and is characterized by a strong dopaminergic input from the midbrain. Dopaminergic neurons seem to convey a feedback signal regarding the profitability of certain actions. In vitro studies have demonstrated that phasic dopamine release can cause potentiation of corticalstriatal synapses. In addition, there is evidence that disruption of basal ganglia circuitry result in problems with learning. METHODS: There are currently no surgical techniques to enhance learning in patients with traumatic brain injuries, strokes, or severe learning disabilities. We used high-frequency microstimulation and fixed-potential amperometry within the anterior striatum of primates actively performing an associative learning task to evaluate whether or not it is possible to modulate learning behavior.

484 | VOLUME 59 | NUMBER 2 | AUGUST 2006

www.neurosurgery-online.com

ABSTRACTS

OF

OPEN PAPERS

892 Endoscopic, Endonasal Extended Transsphenoidal Transplanum Transtuburculum Approach for Resection of Suprasellar Lesions
Theodore H. Schwartz, M.D., F.A.C.S., Vijay K. Anand, M.D. INTRODUCTION: The extended transsphenoidal approach is a less invasive method for removing purely suprasellar lesions compared with traditional transcranial approaches. Most advocates have used a sublabial incision, a microscope, and report a significant risk of cerebrospinal fluid (CSF) leak. We report a series of purely endoscopic endonasal surgeries for resection of suprasellar, supradiaphragmatic lesions above a normal-sized sella. METHODS: A purely endoscopic endonasal approach was used to remove suprasellar lesions in a series of 10 patients. Five lesions were prechiasmal (tuburculum sellae and planum meningiomas) and five were retrochiasmal (4 cranipharyngiomas, 1 Rathkes cyst). The floor of the planum and the sella was reconstructed using a multilayer closure with autologous and synthetic materials. Spinal drainage was used in five of the cases. RESULTS: Complete resection of the lesions was obtained in all but one patient. The pituitary stalk was preserved in all but one patient whose stalk was invaded by a craniopharyngioma and who had preoperative diabetes insipidus. Vision improved postoperatively in all patients who had preoperative vision impairment. Six patients had temporary DI, and five developed permanent diabetes insipidus. Four patients with craniopharyngiomas required cortisone and thyroid replacement. There was one transient CSF leak when a lumbar drain was clamped prematurely. CONCLUSION: A purely endoscopic endonasal approach to suprasellar, supradiaphragmatic lesions is a feasible minimally invasive alternative to craniotomy. With a multilayer closure, the risk of CSF leak is low and lumbar drainage can be avoided. A larger series will be required to validate this approach.

lencing was verified using Western blotting and/or quantitative polymerase chain reaction. Off-target effects were excluded using multiple SiRNAs against each candidate gene. RESULTS: Our analysis revealed that genes known to confer radiation-resistance in cell lines such as Hela, 293T, or primary fibroblasts (ATR, RPA, Histone DeACetylase2 [HDAC2], WEE1, RAD17, RAD9A) are also active in the U87 cell line. Additionally, novel radiation resistance genes not previously reported to influence radiation sensitivity (CDK7, CCNH, KDEL2, MIA, FAP, KIA0101) were identified. CONCLUSION: This study represents the first SiRNA-based approach to identify the genes required for radiation resistance in gliomas. Our results suggest that deoxyribonucleic acid repair pathways uncovered in other experimental systems also operate in the U87 glioma cell line. Pharmacologic inhibition of these pathways or the novel genes uncovered in this study represent potential strategies for cancer treatment.

894 A Phase I Trial of Intracranial Dendritic Cell Immunotherapy for Patients with Malignant Glioma
John S. Yu, M.D., Gentao Liu, Ph.D., Hiushan Ng, M.S., Mia Wagenberg, B.Sc., Anne Luptrawan, M.S.N., Elina Mindlin, B.S., Christopher J. Wheeler, Ph.D., Keith L. Black, M.D. INTRODUCTION: In a preclinical study, we showed that the inoculation of freshly cultured, immature dendritic cells (DCs) into an intracranial tumor results in the generation of a potent antitumor immune response as evidenced by prolonged survival and immunity to tumor rechallenge. METHODS: In this Phase I trial, 23 patients with recurrent malignant glioma (three patients with anaplastic astrocytom and 20 patients with glioblastoma multiforme) with areas of gadolinium enhancement less than or equal to 3 cm in eloquent regions of the brain underwent stereotactic radiotherapy (25 Gy in 5 Gy fractions over 2 wk). Within 2 weeks, these patients underwent subtotal surgical resection and placement of dendritic cells in an area of gadolinium enhancement with guidance from stereotactic navigation. This was a dose-escalation study of intracranial dendritic cell injections. Injection doses were escalated in six cohort groups of three patients starting at 500,000 cells and five patients at the highest dose of 128 million cells. Stereotactic radiotherapy was followed by intracranial injection of autologous dendritic cells, which had been harvested from peripheral blood precursors 1 week prior. RESULTS: There were no common toxicity criteria Grade III/IV toxicities noted that were associated with trial-related procedures. There were no dose limiting toxicities up to 128 million cells. Two out of seven patients who were tested demonstrated a positive cytotoxic T lyphocyte response after intracranial DC administration based on a quantitative polymerase chain reaction assay for IFN- expression. Of the 20 recurrent glioblastoma patients, survival spanned from 9.6 to 132 weeks from the time of their immunotherapy treatment, with a median survival of 48 weeks. Six patients are living, including the first patient treated. Six patients underwent reresection after tumor recurrence following their immunotherapy. One patient demonstrated a prominent lymphoid infiltrate consisting predominantly of cytotoxic T-cells (CD3 , CD8 , CD45RO ) and scattered helper T-cells and B-cells (CD4 , CD20 ). CONCLUSION: These data demonstrate that intratumoral place-

893 A Small Interfering Ribonucleic Acid-based Approach to Characterize Brain Tumor Resistance to Radiation Therapy
Clark C. Chen, M.D., Ph.D., Richard Kennedy, M.D., Alan DAndrea, M.D. INTRODUCTION: The use of radiation therapy in brain tumor treatment has led to improvements in patient survival. However, tumor recurrence from resistance to radiation remains a therapeutic challenge. To address this challenge, we conducted a large-scale small interfering ribonucleic acid (SiRNA) screen to identify genes required for tumor resistance to radiation. METHODS: SiRNA is an experimental tool that can be used to inhibit the protein expression of a target gene. This technology was applied in a large-scale screen to identify genes in the U87 glioma cell line that are required for radiation resistance. U87 cells were plated into 96 well plates, and each well was transfected with SiRNAs directed against different deoxyribonucleic acid repair genes. In total, 712 distinct SiRNA were tested in triplicates. Two days after transfection, the cells were irradiated (10 Gy). Subsequently, cell survival was determined using the Promega Luminescent viability assay. Our study revealed 13 genes that when silenced by SiRNA caused significant radiation sensitivity. The importance of these genes in radiation resistance was confirmed using clongenic survival assays. Gene si-

NEUROSURGERY

VOLUME 59 | NUMBER 2 | AUGUST 2006 | 485

ABSTRACTS

OF

OPEN PAPERS

ment of DCs is safe and results in peripheral T-cell proliferation and intratumoral T cell infiltration in a subset of patients.

895 Chimeric T-cell Receptor Therapy for Glioblastoma Multiforme

Szofia S. Bullain, M.D., Oszkar Szentirmai, M.D., Ning Lin, M.D., Carlos E. Sanchez, M.D., Richard C. Mulligan, Ph.D., Bob Carter, M.D. INTRODUCTION: Epidermal growth factor receptor variant Type III (EGFRvIII) is self-dimerizing, oncogenic, tumor-specific receptor that is highly expressed in glioblastoma multiforme. We describe a clinically viable protocol for the genetic engineering of human T-cells to attack glioma cells expressing EGFRvIII though the use of chimeric T-cell receptor technology. METHODS: The chimeric immune receptor fusion protein (MR1CIR) is composed of two functional entities: MR1, a single chain antibody that specifically binds EGFRvIII, and the human zeta chain of the T-cell receptor that permits major histocompatibility complex independent signaling of the cytotoxic cascade in T-cells that engage EGFRvIII expressing cells. Human peripheral blood mononuclear cells were transfected with MR1-CIR, selected on hygromycin, and expanded to clinically relevant numbers. Stable expression of the MR1-CIR was confirmed by reverse transcription polymerase chain reaction and flow cytometry. Cytolytic capacity of chimeric T-cells was studied by cytotoxicity assays in vitro and by following the growth curves of Gli36-EGFRvIII xenografts stereotactically implanted into immunodeficient mice, with or without intracranial adoptive transfer of MR1-CIR expressing T-cells in vivo. RESULTS: By 12 weeks post transfection, clinically relevant numbers ( 10 9), of MR1-CIR expressing T-cells were obtained, with stable expression of the MR1-CIR shown by reverse transcription polymerase chain reaction and flow cytometry confirming at least 40% surface expression. Cytotoxicity assays confirmed the effective and specific destruction of EGFRvIII human glioblastoma cells (Gli36EGFRvIII). The effector T-cell population was predominantly CD8 with a CD4 subcomponent. In addition, these cells inhibited in vivo tumor growth when adoptively transferred into rapidly growing intracranial EGFRvIII Gli36 cells. Although all control animals died 2 weeks after tumor inoculation, 60% of mice that underwent intracranial transfer of MR1-chimeric receptors and T-cells remained alive. CONCLUSION: Human genetically engineered cytotoxic T-lymphocytes expressing MR1-CIR can recognize and lyse EGFRvIII expressing glioblastoma multiforme cells, inhibit tumor growth, and may prolong survival. The results suggest that a Phase I study of this approach is needed.

radiosurgery between 1991 and 2004. Endocrine cure was defined as a fasting GH less than 2 ng/ml and normal age and sex-adjusted insulin-like growth factor I level (IGF-I) without pituitary suppressive medications. The mean follow-up after radiosurgery was 63 months (range, 22168). RESULTS: Twenty-three patients (50%) had endocrine cure documented at a median of 36 months (range, 663) after one radiosurgical procedure. The actuarial cure rate at 2- and 5-years after radiosurgery was 11 and 60%, respectively. Multivariate analysis showed IGF-I levels less than 2.25 times the upper limit of normal (hazard ratio, 2.995%; confidence interval, 1.26.9; P 0.02) and the absence of pituitary suppressive medications at the time of radiosurgery (hazard ratio, 4.2, 95%; confidence interval, 1.413.2; P 0.01) correlated with biochemical remission. The incidence of new anterior pituitary deficits was 10% at 2 years and 33% at 5 years. CONCLUSION: Discontinuation of all pituitary suppressive medications at least 1 month before radiosurgery significantly improved endocrine outcomes for acromegalic patients. Patients with GH producing pituitary adenomas should not undergo further radiation or surgery for at least 5 years after radiosurgery because GH and IGF-I levels continue to normalize over that interval.

897 Awake Craniotomy for Intraoperative Cortical Stimulation of Language-relevant Areas: Clinical and Neurolinguistic Results of a Prospective, Longitudinal Evaluation of 153 Cases
Maximilian I. Ruge, M.D., Josef Ilmberger, Ph.D., Friedrich-Wilhelm Kreth, M.D., Hanns-Jurgen Reulen, M.D., Joerg-Christian Tonn, M.D. INTRODUCTION: Intraoperative direct cortical stimulation to identify relevant sites for language processing remains the gold standard. Previous studies demonstrated feasibility and usefulness of this method. However, linguistic outcome data are rarely available. In this prospective, longitudinal study (19912005), we report the clinical and neurolinguistic outcome of such patients. METHODS: Patients with lesions within and/or near suspected language-relevant areas were evaluated before surgery, within the first month, and within 1 year after surgery using a test battery for the detection of aphasic disturbances (Aachener Aphasic Test). After intraoperative stimulation and neurolinguistic testing, language relevant areas were marked, and the surgical approach and extent of resection were adapted accordingly. RESULTS: One hundred fifty-three patients were included. Awake craniotomy and stimulation procedure was possible in all patients. Language-related areas could be identified in 93.4% of the patients. The surgical approach and/or extent of resection were modified in 94.9 and 89.2% of the patients, respectively. Prior to surgery, 16.9% of the patients had aphasic disturbances. Early postoperative testing revealed 37.0% disturbances, decreasing to 15.6% within 1 year. The majority ( 60%) of the disturbances were mild. CONCLUSION: Direct cortical stimulation of the languagerelevant areas revealed to be feasible and safe in a routine clinical setting. The surgical strategy could be modified according to stimulation results. Detailed linguistic testing demonstrated temporary and mainly mild aphasic disturbances resolving during follow-up. However, not all aspects of speech and language can be adequately tested during surgery.

896 Factors Affecting Endocrine Cure after Radiosurgery in Patients with Acromegaly
Jeffrey T. Jacob, B.A., Paul D. Brown, M.D., Bruce E. Pollock, M.D. INTRODUCTION: To review outcomes after stereotactic radiosurgery for acromegalic patients and to analyze factors associated with biochemical remission. METHODS: We retrospectively analyed 46 consecutive patients with growth hormone (GH) producing pituitary adenomas having

486 | VOLUME 59 | NUMBER 2 | AUGUST 2006

www.neurosurgery-online.com

ABSTRACTS

OF

OPEN PAPERS

898 Analysis of 445 Patients with Cushings Disease Treated by Transsphenoidal Surgery
Daniel Monte Serrat Prevedello, M.D., Nader Pouratian, M.D., Jonathan H. Sherman, M.D., John Anthony Jane, Jr., B.A., M.D., M. Beatriz Lopes, M.D., Mary Lee Vance, M.D., Edward R. Laws, Jr., M.D. INTRODUCTION: Cushings disease (CD) is one of the most challenging medical conditions to be diagnosed, confirmed, and treated. The authors review 445 patients with CD who were diagnosed and surgically managed in a single institution from 1992 to 2005. METHODS: There were 342 (76.8%) women and 103 men with a mean age of 38.8 years (range 588). Twenty-seven percent of the patients had prior surgical treatment. The mean duration of symptoms before diagnosis was 43.7 months. Common symptoms were hypertension (68.4%), headache (39.5%), and diabetes mellitus (34%). Mean urinary free cortisol was 301 g/24h. Mean adrenocorticotropic hormone (ACTH) was 65 pg/L. Inferior petrous sinus sampling was performed in 53% of the patients, confirming a central source of ACTH. Magnetic resonance imaging scans detected a microadenoma in 49.5% of the patients, a macroadenoma in 5%, and was equivocal in 45.5%. RESULTS: Based on preliminary analysis of 240 patients with more than a follow-up of 2 years, tumor was visualized during 68% of the procedures and suspected in 15%. Total hypophysectomy was performed in 15%, usually those who had severe CD. A fat graft was utilized in 41%. Pathology demonstrated an ACTH staining adenoma in 79%. Postoperative cerebrospinal fluid leak occurred in 2.2%. Surgical remission was achieved in 85.7% of patients with confirmed pathology and in 59.6% when an ACTH adenoma was not verified by the pathologist. Among those who achieved remission, 13% recurred and usually had additional transsphenoidal surgery. In those who did not obtain remission, gamma knife radiosurgery (31%) and adrenalectomy (14%) were the most common adjuvant treatments. The overall management remission rate has been 92% with a mean follow-up of 46 months. CONCLUSION: The treatment of CD demands a multidisciplinary approach. Although it can be challenging, satisfactory results can be obtained when each step in diagnosis and treatment is properly followed.

yet histologically benign brain tumors. Image-guidance was used in the majority of cases, with optimization of power intensity, wave form, frequency, and tissue contact, and with the use of a variety of electrode tips, safe, precise and thorough resections were achieved. RESULTS: Radical resections were achieved in the majority of procedures and were confirmed by postoperative magnetic resonance imaging scans. Lateral thermal tissue destruction was minimized, and no new neurological defects were recorded. Variable characteristics of radio wave surgery include time of tissue contact, power intensity, and wave form, which was dependent on the variety of electrode that was used. The optimization of these characteristics achieved safe, precise, and complete resections in more than 80 brain tumor cases. Collateral damage was minimized with work in direct promixity with delicate structures with controlled hemostasis, dissection, and debulking. CONCLUSION: Using high-frequency, low temperature radiosurgery can be a valuable adjunct for brain tumor surgery, especially when precision and total resection is mandatory.

900 High Incidence of Obesity and Obesity-related Postoperative Complications in Male Patients with Meningiomas
Manish K. Aghi, M.D., Ph.D., William T. Curry, Jr., M.D., Bob Carter, M.D., Frederick George Barker, M.D. INTRODUCTION: The preponderance of females to develop meningiomas may be explained by hormonal stimulation of meningioma growth. Because obesity can affect steroid hormone synthesis in males, we hypothesized that male meningioma patients might exhibit an increased rate of obesity, which in turn might increase the frequency of postoperative complications in male patients with meningioma. METHODS: We retrospectively reviewed 32 male patients who underwent craniotomy for resection of benign meningiomas at our institution between 2001 and 2005. The controls were male patients undergoing initial craniotomy for unruptured aneurysm (n 32) or high-grade glioma (n 32) at our hospital during the same time period. Body mass index (BMI), which is based on the patients height and weight, greater than or equal to 30 kg/m2 was considered obese. Age-specific male BMI percentiles were obtained from National Heart, Lung, and Blood Institute. RESULTS: Despite comparable age (meningioma in 50-year-olds; aneurysm in 53-year-olds; glioma in 52-year-olds), male patients with meningioma had higher average BMI (30.2) than males experiencing aneurysm (BMI, 27.5) or glioma (BMI, 25.9; P 0.04). The obesity rate in male meningioma patients (47%) exceeded that in male patients with aneurysm (19%) or glioma (3%; P 0.02). The age-normalized BMI percentile was greater in male patients with meningioma (median, 67th percentile) than in male patients with aneurysm (49th percentile) or glioma (52nd percentile; P 0.02). Deep vein thrombosis/pulmonary embolus was more common in male patients with meningioma (19%) than in male patients with aneurysm (0%) or glioma (3%; P 0.002). Wound infections were also more common in male patients with meningioma (6%) than in male patients with aneurysm (3%) or glioma (0%; P 0.2). Fifty-three percent of obese patients with meningioma were readmitted with postoperative complications compared with 18% of nonobese patients meningioma (P 0.03). Complications included deep vein thrombosis/pulmonary embolus (27% in obese patients with meningioma, and 12% in nonobese patients with meningioma) and postoperative fever (53% in obese patients with meningioma, and 35% in nonobese patients with meningioma ).

899 High-frequency, Low Temperature Radiosurgery: Adjunct for Brain Tumor Resections
Alfred P. Bowles, Jr., M.D. INTRODUCTION: High-frequency, low temperature radio wave surgery is gaining popularity with many surgical subspecialties including neurosurgery. With radio wave surgery, high-frequency radio waves are directed to tissue through electrode tips. Impedance to passage of radio waves through tissue generates heat within the cells, resulting in volatilization with specific and precise cutting or coagulation. The radiofrequency electrode does not provide resistance and remains cold, limiting collateral damage. The paucity of heat generated at the surgical site allows the surgeon to work in proximity to functional neuroelements. METHODS: During an 8-month period, 90 patients ranging from 20 to 73 years of age were treated for symptomatic brain tumors defined in radiographic and/or clinical progressions. Tumors consisted of cerebral metastases, primary malignant brain tumors, and biologically malignant,

NEUROSURGERY

VOLUME 59 | NUMBER 2 | AUGUST 2006 | 487

ABSTRACTS

OF

OPEN PAPERS

CONCLUSION: We found an increased incidence of obesity in male patients with meningioma, suggesting a possible hormonal influence on meningioma growth in males as well as females. Our results underscore the high risk of postoperative complications in obese male patients with meningioma.

901 Intraoperative Magnetic Resonance Imaging Experience in 700 Patients

Garnette R. Sutherland, M.D., Isabelle Latour, Ph.D., Alexander Greer, B.S.C., John K. Saunders, Ph.D. INTRODUCTION: An intraoperative magnetic resonance imaging system was developed based on a ceiling-mounted 1.5T magnet. A magnetic field strength of 1.5-T was chosen to optimize the signal-tonoise ratio. The system has been used to monitor the outcome of neurosurgery in more than 700 patients. Intraoperative imaging provides anatomical and functional data at any time during surgery. METHODS: The system has been upgraded since 1999 to enhance imaging and facilitate integration with neurosurgery. The system is now marketed by Innovative Magnetic Resonance Imaging Systems Inc. (Winnipeg, Canada) and includes a 1.5-T magnet, highperformance 23mT/m gradients, and Marconi electronics. A radiofrequency coil was developed so that the upper half could be detached from the lower portion between imaging studies. The operating room table is based on hydraulic movement and was built from high-grade materials compatible with magnetic resonance. RESULTS: The patients experienced a full spectrum of neurosurgical pathology. The 264 patients with glioma were the largest group, followed by epilepsy (115 patients) and meningioma (71 patients). Seventy-one patients had vascular pathology. The patients age ranged from 4 months to 84 years, with 11% of the patients younger than 18 years. Planning of surgical imaging updated diagnostic studies, enhanced craniotomy placement and, coupled with surgical navigation, provided precise lesion targeting. In four patients, surgery was aborted, as the target was either significantly reduced in size or not evident. No lesions recurred during a 2-year follow-up. Interdissection imaging showed unsuspected residual target in 10 to 20% of the patients. This was more frequently observed in patients with low-grade glioma, epilepsy, pituitary adenoma, and C1/C2 pathology. Quality assurance imaging provided assessment of the effect of surgery and excluded acute complication. In one patient, acute hemorrhage was evident and removed prior to reversal of anesthesia. CONCLUSION: Based on the results, intraoperative magnetic resonance imaging was found to be a valuable adjunct to neurosurgery. It allows surgeons to determine at any time during surgery the effect of surgical dissection on both the lesion and brain.

within language areas or pathways. We investigated the feasibility of the routine use of subcortical stimulation to identifiy language tracts in a large series of patients with gliomas, to determine the influence that subcortical language tracts identification exerted on the extent of surgery, and to determine the apperance of immediate and definitive postoperative deficits. METHODS: Subcortical stimulation for language tracts identification was systematically used during surgical removal of 44 high-grade gliomas and 44 low-grade gliomas involving language pathways. Procedures were performed during asleep-awake craniotomy. Subcortical stimulation was continuously alternated with surgical resection in a back and forth fashion. Language performances were tested by neuropsychological language evaluation preoperatively and at 3, 30, and 90 days after surgery. RESULTS: Language tracts were identified in 59% of the patients, with differences noted according to tumor location but not according to histological grade. Language tracts identification influenced the ability to reach a complete tumor removal in low-grade gliomas where tracts were documented inside the peripheral mass of the tumor. Identification of language tracts was associated with a higher occurrence of transient postoperative deficits (69.2%), but a low (2.3%) definitive morbidity. A pattern of typical language disturbances related to the phonologic and semantic system can be identified according to tumor location of which preservation is important for the maintenance of language integrity. CONCLUSION: Our study supports the routine use of subcortical stimulation for language tracts identification as a reliable tool for guiding surgical removal of gliomas near or within language areas or pathways.

903 Fiber Tract Navigation in Glioma Surgery

Christopher Nimsky, M.D., Oliver Ganslandt, M.D., Daniel Weigel, M.D., Michael Buchfelder, M.D. INTRODUCTION: To visualize the course of the pyramidal tract in the surgical field during glioma resection by implementation of fiber tract navigation supported by intraoperative imaging. METHODS: In 57 patients with glioma (25 female; 32 male; World Health Organization Grade I, three patients; Grade II, 11 patients; Grade III, 22 patients; Grade IV, 21 patients), a three-dimensional (3-D) object representing the pyramidal tract was visualized in the surgical field. The fiber tract seeding was based on a multiple volume of interest approach, and functional magnetic resonance imaging data identified the motor gyrus as a major start region. A tensor deflection algorithm was used for tracking. The minimum distance between pyramidal tract and glioma was measured in 3-D. Hulls wrapping the fiber tract bundle visualized safety margins. Intraoperative high-field magnetic resonance imaging scans were used to update the fiber tract data, compensating for the effects of brain shift. RESULTS: In all patients, the pyramidal tract could be visualized in the surgical field. In six patients (10.5%), a new or aggravated postoperative paresis could be observed, which was transient in 5 of the patients and permanent in one patient (1.7%). The pyramidal tract in these six patients reached the segmented tumor (total, n 31). The risk in this subgroup for a transient deficit was 19.3% and for permanent defect the risk was 3.2%. No deficits were encountered in the other subgroups that contained 4, 7, and 15 patients (05, 510, and 10 mm distance). Intraoperative diffusion tensor image data were applied for an intraoperative update of the fiber tract information, visualizing a shifting of the pyramidal tract of up to 13 mm.

902 Intraoperative Subcortical Language Tracts Mapping Guides Surgical Removal of Gliomas Involving Speech Areas
Lorenzo Bello, Marica Fava, M.D., Marcello Gallucci, Ph.D., Carlo Giussani, M.D., Giorgio Carrabba, M.D., Francesco Acerbi, M.D., Valeria Songa, M.D., Valeria Conte, M.D., Pietro Baratta, M.D., Nino Stocchetti, M.D., Costanza Papagno, M.D., Sergio Gaini, M.D. INTRODUCTION: Subcortical stimulation can be used to identify functional language tracts during resection of gliomas located near or

488 | VOLUME 59 | NUMBER 2 | AUGUST 2006

www.neurosurgery-online.com

ABSTRACTS

OF

OPEN PAPERS

CONCLUSION: The course of the pyramidal tract can be reliably visualized in the surgical field by integration of fiber tract data in navigational setups. Hulls wrapping the generated 3-D object representing the pyramidal tract represent safety margins. Fiber tract navigation combined with intraoperative imaging, updating the course of the pyramidal tract during surgery, compensated for the effects of brain shift and allowed resections with low morbidity.

904 The Brainstem: A Three-dimenstional Overview of the Superficial Microsurgical Anatomy, Surgical Entry Points, and 4.7-T Magnetic Resonance Imaging Reconstruction of the Intraparenchymal Surgical Corridors. A Cadaveric Database for Future Robotic Surgery and Intraoperative Magnetic Resonance Imaging Application
Ernesto Coscarella, M.D., Mustafa Kemal Baskaya, M.D., Jacques J. Morcos, M.D. INTRODUCTION: We reviewed the anatomy of the fiber tracts and cranial nerve nuclei of the brainstem from a microsurgical point of view and established an anatomical correlate for safe entry zones via the most direct surgical approach. METHODS: Surgical and surface anatomy of the brainstem were studied in injected cadaveric heads. The brainstem was disconnected from the cerebellum, thalamus, and spinal cord in order to study the surface anatomy and safe entry zones. Each brainstem was scanned for 24 consecutive hours with a 4.7-T research magnetic resonance imaging (MRI) scanner to identify fibers and nuclei. The relationship to each possible surgical path was examined through the creation of simulated surgical trajectories. RESULTS: Anatomical and radiological details were obtained. The study demonstrated how the data could be used in planning safer surgical pathways into the brainstem through more logical entry zones. This database could be a platform to be included into an intraoperative MRI system as well as an anatomical interactive map for guiding robotic surgery through eloquent areas of the brain. CONCLUSION: In this preliminary study, we showed the feasibility of high-strength MRI cadaveric imaging of brainstem anatomy. We extended the concept of the surgical application into the study of safer entry zones. The presentation was enhanced by three-dimentional exposition. We predicted a wide application of the technique in the field of surgical education, virtual simulation, and anatomical expositions.

Thirty-three patients (22%) were previously treated, and 117 patients (78%) were previously untreated. Eighty-nine patients (59%) had a single operation, and 61 patients (41%) had more than one operation. Postoperative radiation was given to 33 patients who had residual tumors. Gross tumor resection was accomplished in 59 patients (39%), subtotal resection in 75 patients (50%), and partial resection in 16 (11%) patients. There were no operative deaths. Postoperative complications (cerebrospinal fluid leakage, quadriparesis, infections, cranial nerve palsies, etc.) were observed in 21 patients (14%). Patients were evaluated by questionnaires and review of their recent radiological images. RESULTS: The mean follow-up is 71 months with a range of 3 to 179 months. At the conclusion of the study, 141 patients were alive without disease progression or recurrence. Nine patients (7%) had recurrence (five patients after incomplete resection, four after total resection) of which one died, one underwent repeat resection, and seven were treated by radiotherapy. The Karnofsky Performance Scale score was 78 11 preoperatively, 77 16 at 1 year postoperatively, and 77 15 at the latest follow-up. Common disabilities at follow-up included loss of hearing, Cranial Nerve IV palsy, balance problems, and loss of sensation in Cranial Nerve V distribution. CONCLUSION: Petroclival meningiomas can be managed by complete surgical resection or a combination of surgery and radiotherapy. About 93% of the patients survived without recurrence at long-term follow-up. The functional status of the surviving patients was excellent at follow-up in most patients. This article presents the longest follow-up of petroclival meningiomas in the microsurgical era.

906 Surgical Management of Primary and Metastatic Sarcomas of the Mobile Spine
Ganesh Rao, M.D., Iman Feiz-Erfan, M.D., Indro Chakrabarti, M.D., Milan G. Mody, M.D., Ian E. McCutcheon, M.D., Laurence D. Rhines, M.D. INTRODUCTION: Sarcomas of the spine are challenging due to their extensive involvement of multiple spinal segments and high recurrence rates. Gross total resection with preservation of neurological function and palliation is the goal and may be achieved with either intralesional resection or en bloc resection. We report outcomes of surgery for primary and metastatic sarcomas of the mobile spine in a large series. METHODS: A retrospective review of patients undergoing surgical resection for sarcomas of the spine from 1993 to 2005 was undertaken. Sarcomas were classified by histology and as either primary or metastatic. Details of the surgical approach, levels of involvement, and operative complications were recorded. Survival was the main outcome measure. Secondary outcome measures included recurrent disease, neurologic function, and palliation. RESULTS: Eighty patients underwent 113 surgical resections of either primary or metastatic sarcomas of the mobile spine. Twentyeight patients (35%) experienced primary sarcomas, and 52 patients (65%) experienced metastatic sarcomas. The most common histology was chondrosarcoma (26%). Intralesional resections were performed in 101 surgeries (89%), and en bloc resections were performed in 12 (11%). Median survival was 21.5 months. There was no significant difference in survival between intralesional or en bloc resection (P 0.51). Local recurrence rates were 36 and 16% for intralesional versus en bloc resections, respectively. Complications occured in 13 patients (11.5%). Metastatic disease predicted increased survival in univariate analysis. There was a trend toward significant improvement in American Spinal Injury Association motor scores postoperatively (P 0.08)

905 Patients Outcome at Long-term Follow-up after Aggressive Microsurgical Resection of Petroclival Meningiomas
Sabareesh K. Natarajan, M.D., Laligam N. Sekhar, M.D., Donald C. Wright, M.D., Farrokh Farrokhi, M.D., David Schessel, M.D. INTRODUCTION: To evaluate patients clinical outcome and survival at long-term follow-up after aggressive microsurgical resection of petroclival meningiomas. METHODS: Over a 13-year period (19912003), 150 patients underwent 220 operative procedures for resection of petroclival meningiomas. The tumor size was large to giant in most cases, with a mean tumor diameter of 3.3 1.1 cm. Tumors extended into adjoining regions.

NEUROSURGERY

VOLUME 59 | NUMBER 2 | AUGUST 2006 | 489

ABSTRACTS

OF

OPEN PAPERS

and a significant decrease in pain scores postoperatively (P 0.003) for patients undergoing surgical resection. CONCLUSION: Surgery for primary or metastatic sarcoma of the spine is associated with an improvement in neurologic function and a palliative effect. Treatment for metastatic rather than primary disease was predictive of prolonged survival. Local recurrence rates were lower for en bloc resections; however, there was no significant difference in survival for intralesional versus en bloc resections.

907 Gamma Knife Radiosurgery for Malignant Melanoma Brain Metastases

David Mathieu, M.D., Douglas S. Kondziolka, M.D., MSc, FACS; Patrick Cooper, M.D., John C. Flickinger, M.D., Ajay Niranjan, M.B.B.S., M.S., M.Ch.; Sanjiv Agarwala, M.D., John Kirkwood, M.D., L. Dade Lunsford, M.D. INTRODUCTION: Malignant melanoma is one of the leading causes of brain metastases and is associated with a high rate of neurological morbidity and mortality. Patient survivals rates are lower compared with other metastases due to the limited options for management of active extracranial disease. We reviewed a series of patients who underwent radiosurgery for melanoma brain metastases and assessed clinical outcome to identify prognostic factors for survival and cerebral disease control. METHODS: Two hundred and forty-four patients underwent radiosurgery for the management of 754 metastatic tumors during an 18-year period. A mean of 2.6 tumors were irradiated per procedure. The median total tumor volume was 4.4 cm3. The median margin and maximum doses used were 18 and 32 Gy, respectively. Kaplan-Meier and Cox regression analyses were performed to assess outcome and prognosis. RESULTS: After radiosurgery, the median survival for the entire series was 5.3 months. Improved survival was seen with controlled extracranial disease (12.7 mo), Karnofsky Performance Scale score of 90 or 100% (6.3 mo), single brain metastasis (6.8 mo), total tumor volume less than 8 cm3 (5.8 mo), and absence of cerebellar metastasis (5.6 mo). Persistent local control was achieved in 86.2% of tumors. Increased tumor volume and hemorrhagic lesions were associated with local failure after radiosurgery. Multiple lesions at radiosurgery and absence of subsequent immunotherapy were predictors for the occurrence of new brain metastases, which developed in 41.7% of patients. Symptomatic radiation changes were seen in 6.6% of patients. Overall, 71.4% of patients improved or remained stable after radiosurgery, and 52.4% of patients were able to discontinue or remain off corticosteroids. CONCLUSION: Gamma knife radiosurgery for malignant melanoma brain metastases is safe and effective with a high rate of durable tumor control.

innate and adaptive immune system can eradicate developing tumors. If this process is not successful, then tumor cells enter the equilibrium phase where they may be maintained chronically or immunologically sculpted to produce tumor variants. In this study, we showed that Akt activation was a key step in immune escape for glioma. METHODS: Functional impact of Akt activation was measured using an alloreactive T-cell apoptosis assay. After determining that Akt activation facilitated experimental glioma cell lines and cultures to cause apoptosis of T-cells, we evaluated patient samples in an autologous fashion. Fifteen patients were screened for Akt pathway activation in low passage primary glioma cultures. Autologous peripheral blood lymphocytes were cocultured with matching glioma cultures, and apoptosis of T-cells was measured using flow cytometry and Annexin staining with 7-AAD. RESULTS: Six patients had significant activation of the Akt pathway as measured by Western blotting of the phosphorylated Akt and downstream target S6K1. Coculture of autologous peripheral blood lymphocytes with these six samples resulted in induction of T-cell death (range, 4652%; average apoptosis per sample in triplicate after 2 hour 1:1 coculture; nonspecific stimulation of T-cells, P 0.01 as compared to 9 patients with low Akt activity). Treatment of glioma cultures with wortmannin (a PI3Kinase inhibitor), CCI-779 (mTOR inhibitor), and a direct Akt inhibitor abrogated this effect (1216% average apoptosis, P 0.01). The nine patients with low Akt activity had minimal effect upon T-cells (612% average apoptosis). CONCLUSION: We provided direct evidence from glioma patients that Akt pathway activation in glioma was associated with induction of apoptosis of cocultured T-cells. Our results may explain the failure of T-cell mediated immunotherapy in some glioma patients and provides the impetus for immunotherapy in combination with Akt pathway inhibitors.

909 Changing Trends in the Utilization and Costs of Procedures Performed by Neurosurgeons in the United States.
John A. Cowan, Jr., M.D., William F. Chandler, M.D. INTRODUCTION: Understanding the changes in procedure utilization and total cost associated with the care of patients is important to the practice of neurosurgery. This investigation quantified the overall trends in discharge rates and hospital charges for procedures commonly performed by neurosurgeons in the United States. METHODS: Clinical data was collected from the Nationwide Inpatient Sample for the years 1997 to 2003. Diagnostic related groups that pertain to procedures performed by neurosurgeons (groups 18, 214, 215, 484, 496500, 519, 520, 529532) were used to generate the weighted sample population (estimated n 6,172,258). Discharges and total hospital charges annually for craniotomy, spinal procedures (with and without fusion), peripheral nerve procedures, and extracranial vascular procedures were assessed. Population adjustments were made based on United States Census Bureau data and dollar values were adjusted using the consumer price index for hospital-related services. RESULTS: Overall hospital discharges increased from 823,972 in 1997 to 937,020 in 2003 (14%; P .001). For all spinal procedures, discharges increased from 485,302 to 612,606 (26%; P .001). Of these, 50,042 (10.3%) in 1997 and 310,749 (50.7%) in 2003 were for spinal fusion. Discharges for craniotomy increased from 142,622 to 163,669 (14%) annually (P 0.06). The total charges increased from $10.5 to

908 Akt/PKB Activation Facilitates Immune Escape in Glioma Patients

James Waldron, M.D., Isaac Yang, M.D., Joe C. Murray, B.A., Kristine E. Cachola, B.A., Andrew T. Parsa, M.D., Ph.D. INTRODUCTION: The concept of cancer immunosurveillance has been recently refined to include three steps: elimination, equilibrium, and escape. In the first phase of elimination, cells and molecules of the

490 | VOLUME 59 | NUMBER 2 | AUGUST 2006

www.neurosurgery-online.com

ABSTRACTS

OF

OPEN PAPERS

$20.8 billion for all spinal procedures (P 0.001) and from $7.0 to $10.3 billion for craniotomies (P .001). Peripheral nerve procedures increased by $1 billion (P 0.001), and extracranial vascular procedures decreased by $0.5 billion (P 0.003). CONCLUSION: Spinal procedures experienced large increases in overall utilization and charges during the studied period. There was a

dramatic increase in the number of spinal fusions. Smaller increases were found for craniotomy and peripheral nerve procedures. Extracranial vascular procedures experienced a decline in both utilization and charges. The findings demonstrates the dynamic nature of the contemporary practice of neurosurgery and have implications for future workforce, training, and research needs.

Herbert James Draper in his studio on Abbey Road, (1903).