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845 35C Hypothermia Can Reduce Increased Intracranial Pressure as Well as 33C Hypothermia in Patients with Severe Traumatic Brain InjuryTakashi 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 ModelStacey 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 InjuryAsim 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

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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 PainJin-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 ActivationWilbert 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 PainRichard 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

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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 NeuralgiaNelly 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 StudyJames 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 RadiosurgeryRon 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

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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 HoursLewis 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, IllinoisRichard 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.

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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, 19972003Ziv 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.

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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 NeurosurgeonKevin 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 StudyMing-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 CasesSeref 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

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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 AnalysisManuel 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 CraniopharyngiomasDaniel 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

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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 RatsShenandoah 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 NuancesJustin 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 OutcomePaul 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-

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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 FenestrationNasser 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 DecompressionXiao 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 OutcomeMaureen 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-

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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 InfectionsDaniel 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 InfectionsJody 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 ToolRoberta 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-

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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 CraniosynostosisKimberly 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 PatientsParitosh 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 NucleusSheng-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

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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 MiceViviane 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 ImagingRobert 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 SurgeryHoward 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

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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 PatientsRichard 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 ApplicationsGerhard 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 MonkeysMarina 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.

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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 T