awake craniotomy for intraoperative cortical.144

84535°C Hypothermia Can Reduce Increased IntracranialPressure as Well as 33°C Hypothermia in Patientswith 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 hy-pothermia (48–72 hr) in patients with severe traumatic brain injury(Glasgow Coma Scale scores of 5 or less). In 2000, we altered the targettemperature to 35°C from the former 33°C, as our findings suggestedthat cooling to 35°C is sufficient to control intracranial hypertensionand that hypothermia below 35°C may predispose patients to persis-tent cumulative oxygen debt, which may be associated with an in-creased risk of complications. In this study, we attempted to clarifywhether 35°C hypothermia has the same effect as 33°C hypothermia inreducing intracranial hypertension and whether it is associated withfewer complications and improved outcomes.

METHODS: We compared intracranial pressure and biochemicalparameters of the 30 patients treated with 35°C hypothermia (January2000–June 2005) with those of the 31 patients treated with 33°C hy-pothermia (July 1994–December 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 35°C hypothermia group and 14.9 �10.2 to 20.7 � 12.7 mmHg in the 33°C hypothermia group (P � 0.0669to 0.9903). The incidence of intracranial hypertension (� 20 mmHg) onDays 1 to 7 was 18 to 39% and 18 to 37% of measurements in the 35°Cand 33°C groups, respectively (P � 0.1444–0.9930). Furthermore, our35°C hypothermic patients exhibited a significant improvement in thedecline of systemic oxygen consumption and serum potassium con-centrations during hypothermia, and in the increment of C-reactiveprotein after rewarming. Although the mortality rate tended to belower in the 35°C group (27 versus 48%, P � 0.0801), there were nostatistically significant differences in the incidence of systemic com-plications.

CONCLUSION: The effects of 35°C hypothermia on intracranialhypertension are similar to those of 33°C hypothermia.

846Collagen Scaffolds Populated with Human MarrowStromal Cells Reduce Lesion Volume and ImproveFunctional 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 abil-ity of collagen scaffolds populated with human marrow stromal cells(hMSCs) to reduce lesion volume and improve functional outcomeafter traumatic brain injury (TBI) in rats. No treatment has been foundto be effective in repairing structural loss after TBI.

METHODS: Ultrafoam scaffolds, collagen Type I were obtainedfrom commercial sources and were impregnated with 3x106 hMSCs.Male Wistar rats (n � 24) were injured with controlled cortical impactand divided into four groups. The first group (TBI � scaffold/hMSC)was transplanted with collagen scaffolds populated with hMSCs intothe lesion cavity 4 days after TBI. The other three groups were trans-planted with saline (TBI � saline), scaffolds only (TBI � scaffold) orhMSCs only (TBI � hMSC). Functional outcome was measured usingneurological severity scores and Morris Water Maze. All rats were

sacrificed 35 days after injury and brain sections were stained withimmunohistochemistry.

RESULTS: No improvement in neurological function was observedin the TBI � saline and TBI � scaffold groups; whereas significantimprovement was seen in the TBI � hMSC and TBI � scaffold/hMSCgroups. However, functional improvement was significantly more inthe 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 inlesion volume was seen in the other three groups. In addition, al-though hMSCs were seen in the lesion boundary zone of both theTBI � scaffold/hMSC and TBI � hMSC groups, their number wassignificantly more in the TBI � scaffold/hMSC group showing thatscaffolds enhance the engraftment of hMSCs.

CONCLUSION: Our data demonstrate that scaffolds suffused byhMSCs improve spatial learning and sensorimotor function, and re-duce the lesion volume as well as increase the number of hMSCs intothe lesion boundary zone after TBI compared to saline-, scaffold- andhMSC-treated rats.

847Intrathecal Transplantion of a Human Neuronal CellLine for the Treatment of Neuropathic Pain in aSpinal 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 neuro-transmitter levels are decreased below the level of injury, causing animbalance between inhibitory and excitatory sensory signaling. With-out descending or local inhibition, excitatory pathways such asA-delta and C pain fibers predominate, leading to hypersensitivityand neuropathic pain. SCI that induces behavioral hypersensitivitycan be reproduced in a rat model, using an intraspinal injection of theglutamate receptor agonist, quisqualic acid (QUIS). This model resultsin neuronal loss in the dorsal horn laminae with spontaneous (exces-sive grooming) and evoked (mechanical allodynia and thermal hyper-algesia) behaviors associated with neuropathic pain. We have isolatedand characterized a subclone of the human NT2 cell line, hNT2.17,which differentiates to a neuronal phenotype that secretes inhibitoryneurotransmitters such as �-aminobutyric acid and glycine. Whentransplanted into the subarachnoid space of SCI rats, this cell lineresults in complete recovery from behavioral hypersensitivity afterQUIS.

METHODS: Male Wistar-Furth rats (n � 12/group; Group 1, Na-ı̈ve; Group 2, QUIS-alone; Group 3, QUIS � viable cell transplant;Group 4, QUIS � nonviable cell transplant) underwent QUIS injuryfollowed by intrathecal transplantation of viable and nonviable cells (2wk after QUIS). Behavioral testing (mechanical allodynia and thermalhyperalgesia) was performed weekly for 8 weeks. Evaluation of opti-mal dose was also assessed by transplanting viable cells in varyingdoses (1000, 100,000, and 1,000,000 cells; n � 8/group) in a separateexperimental group.

RESULTS: Animals undergoing viable hNT2.17 cell transplantationdemonstrated complete reversal of all hypersensitivity (P � 0.05). Therecovery occurred 1 week after transplantation and was maintainedfor the entire experiment. Immunohistochemistry confirmed thatgrafted cells were present and synthesizing �-aminobutyric acid. Theoptimal dose for complete and durable behavioral recovery was onemillion cells per transplant graft.

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

848Constitutive �-Aminobutyric Acid Expression via aRecombinant Adeno-associated Virus ConsistentlyAttenuates Neuropathic PainJin-Woo Chang, M.D., Jaehyung Kim, B.A.,Boyoung Lee, Ph.D., Huiran Lee, Ph.D.

INTRODUCTION: Peripheral neuropathic pain, characterized by awide spectrum of pathological processes, is composed of a number ofphenomena occurring at different sites and times, depending on dis-ease states. Among the complex mechanisms underlying neuropathicpain, partial nerve injury seems to result in a selective loss of�-aminobutyric acid (GABA)-ergic inhibitory synaptic currents in thespinal cord. This feature then contributes to the phenotypes of theneuropathic pain syndrome. GABA, the product driven by glutamatedecarboxylase (GAD), is a main inhibitory neurotransmitter in thedorsal horn of the spinal cord and also plays an important role in theventral horn.

METHODS: Previously, we constructed rAAV-GAD65, which ex-presses significantly higher amount of GAD65 and GABA, than con-trolled by the universal CMV promoter. To investigate the beneficialeffects of rAAV-GAD65 treatment, we established a neuropathic painrat model by tibial and sural transection.

RESULTS: The direct administration of rAAV-GAD65 to dorsalroot ganglias induced the constitutive GAD65 expression, whichcould be readily detected by immunocytochemistry. Both allodynicand hyperalesic behavior tests suggested that neuropathic pain mark-edly decreased, along with the transgenic GAD65 expression. More-over, the magnitude of the pain relief maintained for entire experi-mental period, where GAD65 expression was also noticed with nosubstantial reduction in its immunoreactive intensity. Finally, thesignificant amount of enhancement in GABA release after rAAV-GAD65 delivery was identified in vivo by high-performance liquidchromatography.

CONCLUSION: Taken together, the data suggest that the persis-tent GAD65 expression and subsequent GABA release in dorsal rootganglias via rAAV can effectively attenuate peripheral neuropathicpain for long period of time.

849Motor Cortex Stimulation for Chronic IntractableDeafferentation PainRichard K. Osenbach, M.D.

INTRODUCTION: Deafferentation pain syndromes are among themost treatment-refractory pain conditions known. Motor cortex stim-ulation (MCS) has become an accepted procedure for the most refrac-tory patients. We report our initial experience with MCS in 27 pa-tients.

METHODS: The charts of all patients who underwent a trial ofMCS between 1998 and the present were reviewed. All patients expe-rienced chronic intractable pain that was refractory to standard phar-macological therapy including opioids. All patients underwent pre-treatment evaluation by an experienced pain psychologist before

surgery. MCS was performed in two stages. During the first stage, anepidural electrode was implanted over the motor region correspond-ing to the pain topography. A minimum 1-week stimulation trial wasconducted to determine analgesic effectiveness. During the secondstage, patients with a significant reduction in pain were implantedwith an internal pulse generator for long-term stimulation. Patientswho did not derive adequate benefit underwent removal of the elec-trodes. Pre- and postoperative pain scores were recorded in all pa-tients and all patients were asked to estimate the percent pain reduc-tion derived from stimulation.

RESULTS: Pain diagnoses were as follows: trigeminal neuropathic/deafferenation pain (n � 17), post-stroke pain (n � 8), Post-herpeticneuralgia (n � 1), and phantom limb pain (n � 1). The averageduration of symptoms before surgery was 5 years. The averagefollow-up after surgery has been 2 years. For the entire group, theaverage pre- and postoperative visual analog scale scores were 8.7 and4.5, respectively. The average subjective pain reduction was 40%. Forthe 19 patients implanted permanently, average visual analog scalescores were reduced from 7.4 to 2.7. The average visual analog scalescore at the most recent follow-up examination was 3.8, with anestimated pain reduction of 49%. There were no surgical complica-tions. Three patients experienced an isolated seizure during IPG pro-gramming.

CONCLUSION: MCS produces effective pain relief in selectedpatients with intractable deafferentation pain conditions.

850Three Column Contact Patterns for Spinal CordStimulation Offer Selective Dorsal Column FiberActivationWilbert Wesselink, M.Sc., Richard B. North, M.D.

INTRODUCTION: Implantable stimulation systems now drive asmany as 16 independent contacts and can support multiple columnsfor spinal cord stimulation, so as to control for anatomical asymmetryand provide better paresthesia coverage. Three percutaneous catheterelectrodes (“leads”) can be used, with one 1 x 8 compact lead and abifurcated extension connecting two standard 1 x 4 leads, forming aunique “4–8-4” pattern. Similar contact patterns can be fabricated as a“paddle” array for surgical implantation. Contact configurations maybe compared in a computer model, as to their ability to activate dorsalcolumn (DC) versus dorsal root (DR) fibers and energy usage, whilecontrolling for depth of cerebral spinal fluid (dCSF), spacing betweenleads and off midline placement.

METHODS: The University of Twente computer model was usedto predict the effects of electrical stimulation using various contactcombinations and geometries. The modeled configurations (includingan unguarded bipole (UB) or guarded cathode tripole (GC) on a singlelead, and transverse (TTS) or longitudinal (LTS) tripole-like stimula-tion groups on three leads.

RESULTS: For the two values of dCSF modeled, the lowest voltageneeded for activation of the DC fibers is obtained with LTS patterns,followed by GC, UB, and TTS. The best activation ratio of DC to DRoccurs with TTS followed by GC, LTS, and UB. TTS models show thatDC to DR ratio is minimally impacted by increased spacing betweenthe two lateral and midline leads out to 3 millimeters edge-to-edgeseparation. Power needs increase as the spacing narrows.

CONCLUSION: TTS offers the best guarded configuration, activat-ing fibers deeper in the DC before recruitment of DR fibers. LTS offersthe best guarded configuration when attempting to reduce the voltage


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

851Results of Repeat Posterior Fossa Exploration forPatients with Medically Intractable TrigeminalNeuralgiaNelly Amador, M.D., Deborah A. Gorman, R.N.,Bruce E. Pollock, M.D.

INTRODUCTION: Trigeminal neuralgia patients with persistent orrecurrent face pain after microvascular decompression (MVD) typi-cally undergo less invasive procedures in the hope of providing painrelief. 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 (12men, 15 women) underwent repeat PFE. The median interval betweenthe PFEs was 5.9 years (range, 4 d–39 yr). Sixteen patients (62%)underwent one or more other surgeries (median, one surgery) be-tween 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%) hadBurchiel 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 anartery (n � 13, 48%), vein (n � 4, 15%), or Teflon (n � 4, 15%).Notably, four patients (15%) had the cranial nerve seventh-eighthcomplex decompressed at their first surgery. An MVD was performedin 15 patients (56%) and a partial nerve section performed in 12patients (44%). An excellent facial pain outcome (no pain, no medica-tion) was achieved and maintained for 79 and 48% of patients at 1 and3 years after surgery, respectively. Sixteen patients (59%) had new orincreased facial numbness. Two patients (8%) developed anesthesiadolorosa. One patient was deaf after surgery and no patient devel-oped facial weakness.

CONCLUSION: Repeat PFE can be performed safely and has facialpain outcomes comparable to percutaneous needle-based techniquesand stereotactic radiosurgery. Patients with persistent or recurrenttrigeminal neuralgia should be considered for repeat PFE if they areyounger or medically well, especially if other surgeries have notrelieved their facial pain.

852Long-term Outcomes for Trigeminal Neuralgia afterGamma 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 aftergamma knife radiosurgery (GKS) for trigeminal neuralgia (TN) haverelatively short-term follow-up. The few studies that have longermedian follow-up periods often include outliers with relatively short-term follow-up as well. These short-term “outliers” are more likely toreport successful outcomes, which may skew results and make so-called long-term outcomes seem more favorable than they really are.In reviewing our series, we restricted follow-up to a minimum of 36months and rigorously analyzed long-term outcomes for patients withTN after GKS.

METHODS: We reviewed 53 patients with typical, intractable TN

who were treated with a median dose of 80 Gy with one 4-mmisocenter between October 13, 1999 and November 18, 2002. Patientswere placed in five groups based on categories of decreasing success:Group 1A, complete pain relief and off medications; Group 1B, com-plete pain relief and less or same medications; Group 1C, 50% orgreater pain relief and off medications; Group 1D, 50% or greater painrelief and less or same medications; and Group 2, less than 50% painrelief and/or more medications. Patients in Groups 1A–D were col-lectively placed under the “umbrella” of a successful treatment. Pa-tients in Group 2 were considered a treatment failure.

RESULTS: Sixty-four percent of patients had a successful treatmentwith a mean follow-up period of 48 months (range, 36–66 months).The data was subcategorized as follows: Group 1A, 34%; Group 1B,4%; Group 1C, 4%; Group 1D, 23%; and Group 2, 36%. Further dataanalysis showed no differences in outcomes between patients previ-ously treated with microvascular decompression or rhizotomy versuspatients with no previous surgical treatments. Thirty-six percent ofpatients reported some degree of post-treatment facial numbness. Nopatients lost a corneal reflex or developed anesthesia dolorosa.

CONCLUSION: In our series of 53 patients with a mean follow-upperiod of 48 months, 64% of patients had a successful treatment.Thirty-four percent of patients had what we define as a “perfectoutcome,” that is, they had no pain and required no medications.

853Postoperative Continuous Paravertebral AnestheticInfusion for Pain Control in Lumbar Spinal FusionSurgery: A Case-control StudyJames B. Elder, M.D., Michael Y. Wang, M.D.

INTRODUCTION: Patients who undergo lumbar spine proceduresfrequently experience significant, debilitating pain related to theirsurgery. This pain may delay postoperative mobilization, increaselength of hospitalization, and require the prolonged use of high dosesof narcotics. Use of a local anesthetic continuous-infusion pump aftersurgery may lead to improvement in these outcome variables.

METHODS: After posterior lumbar spine fusion procedures, 26consecutive patients received continuous infusion of 0.5% marcaineinto the subfascial aspects of the wound via an elastomeric pump.Data were collected prospectively by third party assessment usingstandard nursing protocols. This included pain scores and opiate useover the first 5 postoperative days, length of hospitalization, andcomplications. Retrospective analysis compared each study patient toa case-control patient. Variables such as age, gender, and surgicalprocedure were similar between matched cases.

RESULTS: Patients receiving continuous local anesthetic infusionused 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 inopiate usage were negligible on postoperative Days 4 (0.04% greater)and 5 (0.07% greater). A lower average pain score was observedamong the study patients on each postoperative day: 23.9% less painon 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 hospitaliza-tion or complications.

CONCLUSION: Patients with a local anesthetic continuous-infusion device used less narcotics than case-control patients over thefirst 3 postoperative days and reported lower pain scores during thefirst 5 postoperative days. These results suggest that continuous infu-sion of local anesthetic into the paravertebral tissue during the imme-diate postoperative period is a safe and effective technique that



achieves lower pain scores and narcotic use. Further data may revealadditional benefits, such as decreased times to mobility and functionalindependence.

854Optimizing Surgical Exposure for NeurosurgicalTrainees 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 haveforced a reduction in trainees’ working hours in all medical special-ties. The conflict between training and service provision needs to berationalized to ensure an adequate level of training for the nextgeneration of neurosurgeons. The majority of emergency operationsrequire generic skills that are rapidly learned. The most technicallydemanding procedures tend to be elective. To determine the mosteffective working pattern for neurosurgical trainees after implemen-tation of reduced working hours we compared operative exposure forvarious working patterns.

METHODS: We conducted an audit of operative data over a6-month period. Six trainees in our unit were placed on two virtualrotations compliant with existing regulations: 1) full shift with 1 weekof 12 hours of night duty with no day duty and the following weektaken as compensatory leave and 2) maximal partial shift with a24-hour duty period followed by a day off in compensation. The aimwas to determine what their operative experience would have beenover a 6-month period.

RESULTS: Trainees on a partial shift rotations would have per-formed a similar number of emergency operations (average, 9; range,5–17), as those on a full shift (average, 11; range, 4–17). Trainees on themaximal partial shift missed 10 (range, 3–23) elective cases, comparedwith 18 (10–31) over the same period for those on full shift, as a resultof enforced absence following periods of duty. These included poste-rior fossa, complex spinal, benign, and rare cranial procedures. Com-parison with a trainee in the 1980s over a period of the the sameduration will also be presented.

CONCLUSION: There now exists a finite period for training toattending level to take place. Careful manipulation of the time avail-able within imposed constraints is essential to ensure that tomorrow’sneurosurgeons are competent in facing the complex challenges ofmodern neurosurgery.

855Is Screening for Deep Venous Thrombosis inAneurysmal Subarachnoid Hemorrhage Patients CostEffective?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 immobi-lization, and significant medical comorbidities put aneurysmal sub-arachnoid hemorrhage (aSAH) patients at risk for deep venous throm-bosis (DVT). Few data exist, however, regarding the cost-effectivenessof screening for asymptomatic DVTs to prevent adverse events in thispatient cohort. We assessed cost-effectiveness of DVT screening byDoppler ultrasonography (USG) in aSAH patients before dischargefrom the intensive care unit.

METHODS: A decision analysis model with a time horizon of 6months was developed to compare expected costs and outcomes ofthree different strategies for DVT detection in aSAH patients: 1)Doppler USG screening of all patients before discharge from theintensive care unit, 2) Doppler USG screening of only Hunt and HessGrade III to V patients, and 3) no screening. Doppler USG wasperformed on all patients when clinically indicated. A retrospectivereview of 178 aSAH patients who underwent screening before dis-charge from the intensive care unit was performed to determine theprevalence of DVT. Additional probabilities and costs (adjusted to2004 dollars) were obtained from the literature. The primary outcomewas the incremental cost-effectiveness ratio. Several variables weretested in one- and two-way sensitivity analysis.

RESULTS: In the base case analysis, the expected cost of screeningStrategy 1 was $618 per patient; screening Strategies 2 and 3 hadexpected per patient costs of $419 and $157, respectively. The moreexpensive programs were associated with small decreases in expectedquality of life and were, therefore, dominated by the no screeningstrategy. This result was preserved in sensitivity analysis across awide range of values for prevalence of DVT and testing characteristicsof Doppler USG.

CONCLUSION: A strategy of obtaining Doppler USG only forclinically suspected DVT in patients after aSAH was found to bedominant in our model, as it was both less expensive and associatedwith higher expected quality of life. This result was robust to varia-tions in the base case assumptions.

856Prospective, Multicenter Evaluation of NeurosurgicalEmergency 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 emer-gency neurosurgical transfers has been noted at academic centers inCook County, Illinois. To determine the cause, a phone survey dem-onstrated a decline in neurosurgery emergency coverage from 44 to84% of Cook County community hospitals over the past 10 years. Toquantify the resulting increase in emergency transfers, determine thetime lapse in transfer, and evaluate the impact on patients, a transferstudy involving all five academic centers in Cook County was per-formed.

METHODS: A multicenter, prosective evaluation of neurosurgicalemergency transfers to Rush, Loyola, University of Illinois, Universityof Chicago, and Northwestern was performed for 2 months in 2005.Institutional review board approvals were obtained. All relevant dataregarding each transfer was collected, including transfer time (definedas time lapse from computed tomographic/magnetic resonance im-aging scan diagnosis to arrival at the accepting institution).

RESULTS: Two hundred thirty emergency transfers were acceptedby the five institutions over the study period. Seventy percent of thesepatients had intracranial hemorrhages; 74% of patients were trans-fered from hospitals without neurosurgery coverage. The mean timelapse from imaging diagnosis to arrival at the accepting institutionwas 5.04 hours (standard deviation, 3.5 hr). Twelve percent of patientsshowed a decline in Glasgow Coma Scale score during transfer. Fivepercent of patients showed a decline of greater than 5 Glasgow ComaScale points during transfer, despite being transferred faster thanpatients without Glasgow Coma Scale decline (P � 0.021).



CONCLUSION: Cook County, including Chicago, is now an un-derserved area in neurosurgical emergency care. This access to careissue and connections to the recent liability crisis in Illinois will bediscussed. Delays in transfer to a center with neurosurgical coverageare long (mean, 5 hr after diagnosis) despite efforts to expedite trans-fers. As a result, 5% of patients experience dramatic deteriorationduring transfer. Further data collected in the study may point tounderlying causes of transfer delays and possible solutions.

857First to Worst: Does Diagnosis-related GroupAssessment 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 ad-mitted with the diagnosis-related group diagnosis of stroke in thestate of Massachusetts. In 2004, T-NEMC had the second higheststroke related mortality in the state. This presentation will evaluatethe stroke-related mortality in patients admitted in 2004 with adiagnosis-related group diagnosis of stroke, to assess whether thisdetermination of quality is useful for assessing the delivery of healthcare.

METHODS: The charts of 31 patients who died at T-NEMC in 2004of stroke-related mortality were reviewed. The cause of death wasdetermined in each case with specific attention to the quality of careprovided. Whether patients were “comfort measures only” or “do notresuscitate” at the time of death was also assessed.

RESULTS: In 2004, 31 in-hospital deaths occurred in 205 patientsadmitted to T-NEMC with a diagnosis-related group diagnosis ofstroke. Included among these 31 patients were 19 with nonoperativemassive intracerebral or subdural hemorrhage, four patients withHunt and Hess Grade 5 subarachnoid hemorrhage, four patients withmassive ischemic stroke, one elderly patient with a small intracerebralhemorrhage with intraventricular extension, one demented patientwith multiple infarcts, and two other patients. Of the 31 patients whodied, 26 were either “comfort measures only” or “do not resuscitate”at the time of death. An additional three patients died of brain deathand another patient was in the process of becoming “comfort mea-sures only” by family discussions. In only one patient was there anerror in the delivery of medical care. Medical treatments that couldhave prevented an in-hospital death, but not improved quality of life,will be discussed.

CONCLUSION: There is increasing interest in the quality of healthcare. “Quality” will be used to determine patient referrals, insurancecontracts, and rating individual physicians. However, using hospitalmortality rates by diagnosis-related group in stroke patients probablyis not a good measure of quality. Neurosurgery needs to developmeans for determining true measures of quality in health care deliv-ery.

858Racial and Socioeconomic Disparities in the SurgicalTreatment of Parkinson Disease in the United States,1997–2003Ziv 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 surgicalParkinson disease (PD) treatment relative to racial and socioeconomicpatient variables.

METHODS: A retrospective cohort study was performed using theNationwide Inpatient Sample, 1997–2003. Multivariate logistic regres-sion was used to model selection for surgical PD treatment withgeneralized estimating equations used to adjust for within-hospitalclustering.

RESULTS: A total of 2460 patients with diagnosed PD under-went surgical treatment at 96 hospitals (1883 neurostimulator, 577thalamotomy/pallidotomy). Of surgically treated patients, only0.7% were African-American. Comparatively, 12% of the UnitedStates population is African-American, and the incidence of PD forAmericans of European and African heritage is estimated to besimilar (13.6 and 10.2 per 100,000 persons/year, respectively). Wecompared surgically-treated patients to 11,242 patients with PDadmitted to the same hospitals who did not receive surgical PDtreatment to determine patient-related factors associated withtreatment. Adjusted for age, treatment year, and expected primarypayer, African-Americans had a significantly lower chance of re-ceiving any surgical PD treatment (odds ratio, 0.29; 95% confidenceinterval, 0.18–0.49; P � 0.001) or receiving a neurostimulator (oddsratio, 0.29; 95% confidence interval, 0.17–0.49, P � 0.001). OfAfrican-American patients, 52% were admitted to hospitals per-forming fewer than four cases per year, compared with 34% forother patients (P � 0.001). In contrast to surgical PD treatment, Af-rican-American inpatients were more likely to receive gastros-tomy (12%), another common surgical procedure in PD, suggestingthat not all surgical procedures are underrepresented in thispopulation. Finally, patients with private or Medicare insurancewere more likely to receive surgical PD treatment and neurostimu-lator placement than Medicaid patients (P � 0.01 and 0.03, respec-tively).

CONCLUSION: These findings suggest that African-American pa-tients with PD are significantly less likely to receive neurosurgical PDtreatment of any kind, including neurostimulator placement. Certaintypes of medical insurance are also significantly associated with treat-ment selection. Factors that may play a role in these disparities includereferral patterns, patient preferences, socioeconomic status, and phy-sician bias.

859Is the Current Model of “Academic” NeurosurgerySustainable?Dongwoo J. Chang, M.D.

INTRODUCTION: At the October 2005 Congress of NeurologicalSurgeons meeting, the author preliminarily reported on a 125-neurosurgeon 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 thepractical realities of functioning as a neurosurgical academician. Theauthor now reports further on the analyzed data and suggests analternative funding plan as a way to actualize the goals of the tradi-tional academic missions.

METHODS: Confidential Email questionnaires were sent to full-time academic neurosurgeons in the United States.

RESULTS: The vast majority of academic neurosurgeons are notsubspecialized (with most of the “subspecialized” neurosurgeonsfocused on spine) and spend most of their time in direct patientcare. This is compounded by minimal neurosurgery resident in-volvement in the outpatient clinic and suboptimal resident involve-



ment surgical procedures. Seventy-six percent of the academicneurosurgeons reported significant institutional pressure to in-crease professional billings, whereas most (82%) spent less than15% of their total work time on research and writing. Interestingly,most academic neurosurgeons preferred salary compensationbased on clinical “productivity” and promotions based on scholarlycontributions.

CONCLUSION: The current academic neurosurgical model is un-sustainable, particularly in the modern era of medical economics. Adirect conflict of interest is created because concrete “rewards” aregiven primarily for billable work, even though, in academia, all mis-sions should have great emphasis. The author suggests a publicly-funded model of academic neurosurgery that would allow compen-sation on mission-based activities, similar to the Alternative FundingPlan being used by some of the Canadian regional academic healthcenters. A publicly-funded mandate would make the greater societyaccountable for the future vitality of the neurosurgical disciplinerather than letting “academic” neurosurgeons “sink or swim” in anunsustainable situation in an era rampant with financial, legal, andlogistical pressures.

860Effects of Socioeconomic and Geographic Variationson 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 withglioma, data of 30,489 patients from the Cancer Registry in Englandand Wales are analyzed.

METHODS: Median survival and crude survival rates for eightvariables (age, sex, International Classification of Diseases for Oncol-ogy (ICD-O) morphology, World Health Organization (WHO) grade,tumor site, SES, geographical regions, and periods of diagnosis) arecalculated using the Kaplan-Meier method. Distributions among dif-ferent variables are compared using the �2 test. Cox multivariateregressions are performed for estimating hazards ratios (HR) to death.

RESULTS: The median survival and the 1, 5, and 10-year crudesurvival rates in this population are 0.42 years, and 29.1, 12.0, and7.7%, respectively. There is a gradient in SES from the south to thenorth (�2 test, P � 0.001) and a gradual increment in higher SES fromthe early to the recent period (�2 test, P � 0.001). Mono- and multi-variate analyses reveal that the survival is influenced by all eightvariables (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 mor-phology (HR, 1.23–1.89, compared with ependymoma, P � 0.05) arethe three most powerful factors. However, there are independenteffects of SES (HR, 1.03/quintile of deprivation, P � 0.001) and geo-graphical regions (HR, 1.10 for outside the Southern England, P �0.001) on survival for these patients.

CONCLUSION: Although age and tumor characteristics (ICD-Omorphology, WHO grade, tumor site) are well-known prognosticfactors determining the survival for adult patients with glioma, SESand geographical variations also play significant roles. For more cost-effective allocation of health resources, investments on these twomodifiable factors should be considered.

861Pediatric 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 agegroups is becoming increasingly common. Despite significant ad-vances in the understanding and treatment of adult spinal disorders,the literature concerning pediatric back and neck pain is sparse. Thisstudy examines the presentation, etiology, and treatment of pediatricspine pain.

METHODS: Two hundred fifty consecutive patients were seen at amultidisciplinary pediatric spine center. Patients were evaluated andmanaged by a team consisting of a pediatric neurosurgeon, a pediatricinterventional spine physician, and a pediatric physical therapist.Standardized questionnaires were used to collect historical and sub-jective data. Team consensus determined physical examination find-ings, diagnosis, and treatment.

RESULTS: One hundred ninety patients (76%) had a chief com-plaint of spine pain at an average age of 13.23 years. Trauma wasnoted in 38.42%, with motor vehicle collisions being the most commoninciting event (31.51%). Thoracic pain was less common than cervicalor lumbar (12.11 versus 37.89 and 39.47%), but more commonly asso-ciated with surgical pathology. Neurological deficits were found in25.26%, most commonly sensory (47.92%). Before referral, 48.42% hadundergone at least one magnetic resonance imaging scnas, whereasonly 11.05% had undergone physical therapy. On average, pain hadbeen present for 8.81 months before referral, during which 50% noteda negative effect on physical activity and 23.16% noted a negativeeffect on school performance. The most common diagnosis was myo-fascial pain (33.68%) followed by lumbar herniated disc (13.68%).Chronic myofascial pain was aggressively treated and 95.31% notedimprovement with stabilization therapy and electrical muscle stimu-lation. Surgical pathology was found in 26.84%, most commonlyherniated lumbar disc and C1–C2 instability.

CONCLUSION: Pediatric spine pain is common. Aggressive treat-ment of myofascial pain is highly effective. More than one-quarter ofthe children with spine pain will harbor surgical pathology, whichdemands a central role for pediatric neurosurgeons in the evaluationand management of pediatric spine pain.

862Thoracolumbar and Sacral Spine Injuries inChildren 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 tho-racic, lumbar, and sacral injuries. Guidelines for the management ofthese injuries are missing. This study reviews our experience withthese injuries in children to determine the mechanism, patterns ofinjury, and factors affecting management and outcome. This repre-sents the largest study of its kind in the literature.

METHODS: Between 1997 and 2005, 89 (46 boys and 43 girls; meanage, 13.2 yr; range, 3–16 yr) patients with thoracic, lumbar, and sacralinjuries (total of 141 fractures) with and without spinal cord injurywere treated. Eighty-two were between 9 and 16 years of age, and



seven were between the ages of 3and 9 years. We evaluated the leveland pattern of injury, diagnosis, neurological function (Frankelgrade), associated injuries, radiographic findings, and outcomes.Follow-up assessment included clinical evaluation and radiographicstudies.

RESULTS: Injuries included fracture, fracture/dislocation, disloca-tion, and ligamentous injury. The lumbar region was most frequentlyinvolved while the sacrum was the least frequently involved. Overall,90% of patients were neurologically intact, 3.3% had incomplete spinalcord injury, and 6.7% had complete spinal cord injury. Treatment wasnonsurgical in 66 (74%) of the patients, and surgery was performed in23 (26%) patients (anterior approach in six, posterior approach in 16,and a combined approach in one patient). Stable fixation and main-tenance of alignment were demonstrated in all 23 patients who un-derwent surgical treatment. Postoperatively, four patients (30.7%)with neurological deficits improved.

CONCLUSION: Thoracic and lumbar spine injuries occur mostcommonly in children older than 9 years of age and are mainly locatedat L2–L5. Multilevel injuries are common and warrant radiologicalworkup of the entire spinal column. Most patients can be treatedconservatively, although both posterior and anterior approaches areeffective. Patients with spinal cord or multilevel injuries can developspinal deformity and should be followed closely.

863Is Multifocal Seizure Resection in ChildrenReasonable?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 tomonofocal, rather than multifocal, epilepsy. However, in pediatricpatients in whom developmental issues and the ability to performdaily 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 usedthis philosophy to approach a cohort of children with two or moreseizure foci by resecting multiple foci and evaluating outcome.

METHODS: Charts of 50 consecutive children who underwentsubdural electrode electroencephalographic monitoring followed bysecond surgery for seizure focus resection were reviewed. Three pa-tients were lost to long-term follow-up.

RESULTS: Nineteen patients underwent resection of two or morefoci (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 focusresection 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 bothgroups, there were improvements in activities of daily living, schoolperformance, and subjective assessment of the care team.

CONCLUSION: Although seizure elimination was twice as likelyin monofocal resection patients versus multifocal patients (EngelGrade 1, 67 versus 32%), we found that seizure control outcomes werecomparable between these two groups when Engel Grade 1 and 2results were combined (78 versus 80%). These observations suggestthat, if seizure reduction (as opposed to elimination) can improvedevelopment/function in a child, then resection of multiple seizurefoci may be as reasonable an approach as monofocal resection.

864Medulloblastoma Subtypes Defined by GeneExpression AnalysisManuel Ferreira, M.D., Ph.D., Scott L. Pomeroy, M.D.

INTRODUCTION: Medulloblastomas are the most common type ofmalignant pediatric brain tumor. After surgery, therapy consists of high-dose chemotherapy and cranial-spinal radiation. Survival is associatedwith neurological sequelae owing to this aggressive therapy. Histopatho-logical classification of medulloblastomas into the desmoplastic or classicsubtypes has not been found to correlate with outcome, whereas clinicalcriteria have (e.g., metastasis). This usually guides postoperative treat-ment. Our group showed gene expression profiling to be highly predic-tive of response to therapy, predicting outcome with much greater accu-racy than current staging criteria. This proved to be an accurate way ofdifferentiating between certain embryological brain tumors (teratoid,rhabdoid, peripheral neuroectodermal, glioma, and medulloblastoma).This could become a way, based on the genetic “fingerprint” of a me-dulloblastoma, for risk stratification.

METHODS: We used deoxyribonucleic acid microarray gene ex-pression data (Affymetrix HuGeneFL 6800 arrays) from 74 medullo-blastomas, five central nervous system teratoid/rhabdoid tumors, 10malignant gliomas, and four normal cerebellums. Analysis was per-formed by principal component analysis, non-negative factorization(NMF) and gene set enrichment analysis.

RESULTS: This method of classification proved useful when dif-ferentiating between embryological tumor types. Using NMF analysisfrom 74 medulloblastomas, we found that they segregated into fivesubgroups. One group (NMF1) was made up of the desmoplastictumors in the dataset. The classic tumors were divided into fourdistinct subgroups (NMF2–NMF5). We applied gene set enrichmentanalysis methodology to the five NMF classes and found that the sonichedge hog signaling pathway was enriched in NMF1, consistent withour previous work. The other NMF groups comprising classic tumorswere identified by signature gene sets.

CONCLUSION: By using deoxyribonucleic acid microarray expres-sion data, we identify subgroups of medulloblastomas that are differen-tiated based on their genetic “fingerprint.” This may prove invaluable forguiding therapy (risk stratification), quick assaying for risk stratificationat the time of diagnosis, new molecular targets, and drug discovery.

865Transsphenoidal Surgery in the Treatment ofPediatric 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 commonsellar/parasellar tumors in the pediatric population. The transsphe-noidal resection of pediatric craniopharyngiomas is controversial.

METHODS: A neuropathology database was reviewed from 1992to 2005; 21 pediatric craniopharyngioma patients (age � 18 yr) wereidentified. Clinical records and imaging were reviewed. The mean agewas 11.1 years (range, 2.5–17.5 yr) and the mean follow-up period was34.1 months. Most patients (n � 19, 90.5%) had sellar and extrasellardisease. Tumor size ranged from 13 to 52 mm. Ten patients hadundergone previous treatment, of whom all had undergone at leastone craniotomy. Common preoperative findings included endocri-nopathy (90.5%), growth delay (57%), headache (71.4%), visual field



impairment (57.1%), optic atrophy (28.6%), diabetes insipidus (61%),and hydrocephalus (14.2%).

RESULTS: Gross total excision was accomplished in 76.2% and radicalsubtotal excision in 9.5% of the patients. A fat graft was required in 20patients (95.2%) to repair the cranial base. Visual improvement occurredin 23.1% and normalization in 46.2%. Optic atrophy predicted failure tonormalize vision (P � 0.01). Vision was transiently worsened in onepatient and permanently affected in another (right temporal visual fielddefect). Postoperative cerebral spinal fluid leak occurred in two patients(9.5%), requiring repeat surgery for repair. There were no cases of men-ingitis. Four patients (44%) had transient and four (44%) new permanentdiabetes insipidus. Three (50%) developed new panhypopituitarism. Onepatient, who had a previous history of postcraniotomy stroke, had an-other brain infarct 20 days postoperatively and died. Three patients(14.3%) developed recurrence at a mean of 25.1 months. One patient hasbeen observed, one underwent gamma knife radiosurgery, and oneunderwent a second transsphenoidal operation. At the last follow-upexamination, 71.4% of patients were living and well, 23.8% were livingwith partial visual deficit, and one patient (4.7%) died of disease progres-sion.

CONCLUSION: The transsphenoidal approach provides a reason-able alternative to craniotomy for the treatment of selected pediatriccraniopharyngioma patients.

866Surgical Targeting and Focal Implantation of GeneTherapy for Global Neurological Disease: OperativeTechnique 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 cur-rently under transition from bench to bedside. Only one previoushuman trial has attempted gene therapy for a global neurogeneticdisorder. The requirements for global delivery present unique neuro-surgical challenges, which differ from those seen in previous single-site infusion studies.

METHODS: Nine patients with Batten’s disease underwent focalinfusion of an AAV2 vector containing a normal copy of the ceroid-lipofuscinosis, neuronal 2 gene through 12 injections (two/injectionsite) in the cerebral cortex. Operative technique was studied to assessefficiency. Patients were studied with postoperative magnetic reso-nance imaging scans to evaluate vector delivery.

RESULTS: The degree of cerebral atrophy was substantial com-pared with normal patients at this age. Frameless stereotaxy was usedfor trajectory planning and burr hole placement to avoid delivery intothe subarachnoid space. This accurately predicted gyral locations innearly all burr holes. Twenty-gauge spinal needles used as guidetubes for borosilicate infusion catheters were fixed along trajectoriesusing the Sugita headframe, with the needle tip just deep to the pia.This permitted accurate placement of the infusion catheter at the twodepths along each tract. Burr holes were filled with fibrin glue afterfixation of the guide needle, to minimize cerebrospinal fluid loss. Nopostoperative hemorrhages were noted. A radiographic correlate ofinjection was recognized in 70% of sites, though the sensitivity ofmagnetic resonance imagin scans to detect vector infusion is, as yet,unknown.

CONCLUSION: Effective clinical translation of central nervoussystem gene therapy requires the development of novel deliveryapproaches that have not been part of traditional neurosurgical prac-tice. Several novel methods, which were distinct from our previoushuman experience with focal gene therapy, were required here formore global gene delivery. These results indicate that relatively accu-rate infusion to multiple sites simultaneously can be achieved withminimal cerebrospainl fluid loss or brain shift and without significantsurgical complications.

867Restoration of Impaired Neurodevelopment afterSystemic Prenatal Brain Injury in RatsShenandoah Robinson, M.D.

INTRODUCTION: Systemic perinatal insults cause cerebral palsyand epilepsy in children born preterm. We propose that impairedneural development from prenatal insults includes �-aminobutyricacid (GABA)-ergic neuronal loss and is partially reversible usingneonatal neuroprotective agents.

METHODS: In rats, transient uterine artery occlusion was per-formed on embryonic Day 18 for 45 or 60 minutes to mimic pretermhuman insults. Sham-controls had surgery without arterial occlusion.Pups were born at term. Motor tests were performed in neonates andadults. Pentylenetetrazol (PTZ), a GABA-ergic antagonist; NM.D.A, aglutamate agonist; and pilocarpine, a muscarinic agonist, were used tolower the seizure threshold in adult rats. Latency to each of threeseizure grades was recorded. Tissue was collected for in vitro, ana-tomic, and biochemical assays. Immunolabeled cells were counted oncoronal sections in a blinded manner. Erythropoietin (2000 U/kg) wasadministered intraperitoneal on postnatal Days 1 to 5, with salinecontrols. Comparisons were made using two-tailed t or �2 tests, withP values less than 0.05 considered significant.

RESULTS: After a prenatal insult, rat pups and adults showedimpaired motor skills compared with sham-controls (P � 0.02). PTZlowered the seizure threshold in insult rats, whereas other nonGABA-ergic convulsants did not. Lower PTZ doses were required to induceall seizure grades in postinsult rats, compared with sham-controls (P� 0.03). In adult postinsult rats, GABA-ergic subpopulation neuroncounts including neuropeptide Y and parvalbumin were significantlydecreased in multiple cortical areas (P � 0.03). Erythropoietin par-tially reversed neonatal brain damage and raised the seizure thresholdin mature insult rats, compared with saline-treated controls.

CONCLUSION: These results suggest impaired cortical develop-ment after perinatal injury in premature infants is owing, in part, tocortical GABA-ergic neuronal loss, and that this deficit is partiallyrestored by neuroprotective agent administered in the neonatal pe-riod. These results demonstrate sustained erythropoietin-induced im-provement in adults after a prenatal insult, a novel therapeutic strat-egy for perinatal brain injury.

868Pediatric Cerebral Aneurysms: Characteristics,Pathogenesis, Surgical and EndovascularManagement, 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 beendemonstrated in children with aneurysmal subarachnoid hemor-



rhage, it is generally felt that vasospasm is well tolerated withoutassociated neurological deterioration. We present our series of pedi-atric cerebral aneurysms treated with surgical clipping and endovas-cular techniques. We also describe two cases of severe, medicallyrefractory clinical vasospasm, which were successfully managed en-dovascularly. Pathological specimen were reviewed for further eluci-dation 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 Hos-pital. Medical records and radiographic studies were reviewed todetermine patient demographics, clinical presentation, radiographicfindings, treatment, and outcome.

RESULTS: Ten patients underwent craniotomy for aneurysm clip-ping. Seven of these presented with subarachnoid hemorrhage. Onpresentation, five were Hunt and Hess Grade III, one was Grade II,and one was Grade V. Two patients with ruptured anterior commu-nicating artery aneurysms exhibited worsening hemiparesis and men-tal status with severe angiographic vasospasm, which resolved afterseveral endovascular treatments with papaverine and nicardipine.Two patients with basilar artery dissecting aneurysms underwentendovascular management with successful outcomes. All patients hadexcellent outcomes (Glasgow Outcome Scale 5), except for one whodied after surgery (Hunt and Hess Grade V with complex middlecerebral artery aneurysm). In one pathological specimen, a segment ofthe parent vessel adjacent to the aneurysm neck exhibited fragmen-tation of the internal elastic lamina and muscularis layers, supportingprevious reports.

CONCLUSION: In contrast to previous reported series of pediatricaneurysms, we found a relatively high incidence of symptomaticvasospasm with neurological deterioration that was successfullytreated with interventional management.

869Recovery, Improvement, and Complications afterEndoscopic versus Conventional Open ChiariDecompressionXiao Di, M.D., Ph.D., Mahamoud G. Ammar, M.D.,Mark G. Luciano, M.D.

INTRODUCTION: Endoscopic chiari decompression allows bonydecompression through a 2-cm incision. The small incision and de-compression have a potential of faster, limited, and less complicatedrecovery. This study compares the recovery rates from preoperativesymptoms, duration of hospital stay, postoperative complications,and recurrence after endoscopic versus nonendoscopic open proce-dure.

METHODS: We retrospectively reviewed the records of all patientswith Chiari Type I malformation who had undergone initial suboc-cipital craniectomy and upper cervical (C1, C2) laminectomies forChiari decompression between January 1995 and December 2005.Patients were allocated to a nonendoscopic group whose procedurewas performed with the assistance of surgical loupes and a micro-scope and to an endoscopic group whose procedure was operateddirectly under 0- or 30-degree endoscopes. Improvement (excellent,partial, no change, and worse) after surgery, hospital stay, postoper-ative complications, and preoperative symptomatic recurrence wereanalyzed via the �2 and Kaplan Meier tests.

RESULTS: There were 148 patients who underwent Chiari decom-pression from January 1995 to December 2005. Among these, 38patients (25.7%) underwent endoscopic procedure in the past 2 years.

Improvement (excellent and partial) was 83.8% in endoscopic proce-dures versus 72.7% in the open surgical group. The duration ofhospitalization was 3. 6 versus 8.9 days, the rate of complications was7. 9 versus 29.1%, and the rate of recurrence requiring surgery was 8.2versus 0%, respectively.

CONCLUSION: Endoscopic Chiari decompression significantlydecreased the chance of complications, shorten hospitalization, andimprove postoperative recovery when compared with the conven-tional open procedure. Acknowledging of the limit of retrospective,nonblinded, and nonrandominzed study, we suggest further evalua-tion of endoscopic bony Chiari decompression.

870Multiloculated Hydrocephalus: A Study of 24Patients Operated by Endoscopic Cyst FenestrationNasser M.F. El-Ghandour, M.D.

INTRODUCTION: The treatment of multiloculated hydrocephalusis a difficult problem in pediatric neurosurgery. Definitive treatmentis surgical, yet the approach remains controversial. We have, there-fore, reviewed our results with endoscopic cyst fenestration (ECF) inthe management of this disease.

METHODS: We present the largest series to date of multiloculatedhydrocephalus operated by endoscopy (24 patients). Uniloculatedhydrocephalus is not included in this study because it is a differententity that would be better studied separately. Surgical treatmentincluded ECF (24 patients), endoscopic revision of malfunctioningpreexisting shunt (6 patients), placement of new shunt (15 patients),and third ventriculostomy (3 patients).

RESULTS: The group included 10 males and 14 females with amean age of 12.5 months. Neonatal meningitis was the most commoncause (9 patients), followed by intraventricular hemorrhage (6 pa-tients), postoperative gliosis (6 patients), and multiple neuroepithelialcysts (3 patients). Multiplanar magnetic resonance imaging scansmake early diagnosis and are indicated if the computed tomographicscan shows disproportionate hydrocephalus. ECF was easily per-formed in all cases with devascularization of cyst wall by coagulationto prevent recurrence. The results are encouraging, with improvementof hydrocephalus in 18 patients (75%). The need for shunting wasavoided in three patients (12.5%). Endoscopy reduced the shunt revi-sion rate from 2.9 per year before fenestration to 0.2 per year afterfenestration. During the mean follow-up period (30 months), repeatECF was necessary in eight patients (33.3%). Six out of these eightpatients (75%) were already shunted before endoscopy. Endoscopiccomplications were minimal (two cerebrospinal fluid leakage, twominor arterial bleeding) and no mortalities (0%).

CONCLUSION: ECF is recommended as the procedure of choice inthe treatment of multiloculated hydrocephalus because it is effective,simple, minimally invasive, and associated with low morbidity andmortality rates.

871Shunting 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 docu-mented in individuals with hydrocephalus. Previous research indi-



cates that both children and adults experiencing hydrocephalus dis-play deficits in memory function, language fluency, nonverbal skills,and strategic planning. However, patients who undergo early surgicalintervention often show improvements in memory function and lan-guage fluency, yet frontal lobe dysfunction often persists. Scant re-search examines the impact of surgical procedure on long-term cog-nitive outcome. The current study examines neurocognitive outcomerelated to different treatment interventions for hydrocephalus.

METHODS: Thirty-two adults who underwent surgical interven-tion for hydrocephalus completed a neuropsychological battery.Twenty-four patients with a programmable valve shunting systemwere compared with eight individuals with a nonshunting obstructivebypass system (endoscopic third ventriculocisternostomy, ETV)across the test battery.

RESULTS: Inspection of data revealed that scores for both groupswere consistently one standard deviation below normative means,despite normal estimates of premorbid intellect. Independent samplet tests revealed significant group differences on the Mini-Mental StateExamination (P � 0.01) and several measures of executive functioning(P � 0.03). Specifically, the ETV patients performed at least onestandard deviation below the shunted patients on measures of plan-ning and inhibition. In addition, a trend towards better performanceon memory measures was noted within the shunted group whencompared with ETV patients.

CONCLUSION: Individuals who underwent shunting within thefirst year of life and individuals who underwent ETV more than 1 yearago continue to display mild cognitive inefficiencies in adulthood,regardless of age or emotional status. Inspection of the data revealedsignificant memory retrieval and speeded mental processing deficits,along with subtle executive inefficiencies. There was a significantdifference between the groups on a global measure of cognition, alongwith several executive tasks. We theorize that the enlarged ventriclesafter ETV may disrupt frontal networks, rendering them at a higherrisk for subtle cognitive dysfunction than shunted patients.

872Antimicrobial Suture Use Associated with aDecreased Incidence of Cerebrospinal Fluid ShuntInfectionsJody Leonardo, M.D., Curtis J. Rozzelle, M.D.

INTRODUCTION: Implantation of cerebrospinal fluid shuntingdevices is associated with a 5 to 10% risk of infection, as cited in thecontemporary pediatric neurosurgical literature. Shunt infections typ-ically require complete removal of the device and prolonged antibiotictreatment followed by shunt replacement. Moreover, shunt infectionsare commonly associated with prolonged hospital stays, potentialcomorbidity, and the increased risk of neurological compromise ow-ing to ventriculitis or other shunt-related complications.

METHODS: A prospective, randomized, double-blinded study iscurrently underway at our institution. Newly diagnosed and estab-lished hydrocephalus patients are randomized at the time of shuntsurgery into study and control populations with wound closuresperformed using antimicrobial absorbable suture (Vicryl-Plus, Ethi-con, Inc., Somerville, NJ) or standard absorbable suture (Vicryl, Ethi-con, Inc.), respectively. Randomization is categorized so that factorsknown to influence infection risk are equally represented in bothgroups. Additional data recorded pertains to demographics, surgicalhistory, infection history, body habitus, and antibiotic use to facilitatepost hoc analysis. Study and control patients receive identical pre-,

intra-, and postoperative care with the presence or absence of shuntinfection after 6 months as the primary outcome measure.

RESULTS: To date, 44 patients have been enrolled for a total of 47shunt procedures. The study group numbers 24 procedures and thecontrol group 23. No shunt infections have occurred in the studygroup, whereas four shunt infections have been diagnosed and treatedin the control group. Right-tailed Fisher exact analysis of this distri-bution supports statistical significance (P � 0.050) with a relative riskreduction of at least 18.7% (95% confidence interval, 0.187–infinity).

CONCLUSION: Preliminary data analysis suggests that the use ofantimicrobial suture for shunt surgery wound closure is associatedwith a lower incidence of postoperative shunt infections.

873Prolonged Exposure to Antibiotic-impregnated ShuntCatheters does not Increase the Incidence of LateShunt 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) systemshave been designed to prevent the colonization of shunt componentsby skin flora that occurs at surgery. Although such systems maydecrease the incidence of early shunt infections (those occurringwithin 6 months of shunt placement), it is unclear if such exposure toprolonged antibiotics leads to an increased incidence or virulence oflate shunt infections (those occurring longer than 6 months after shuntplacement). In this study, the authors evaluate the incidence of lateshunt infection after the introduction of an AIS system in a pediatrichydrocephalus population.

METHODS: We prospectively reviewed all pediatric patients un-dergoing antibiotic-impregnated cerebrospinal fluid shunt insertionor shunt revision operations at our institution for the 33-month periodbetween October 1, 2002 and June 31, 2005. All shunt-related compli-cations, including shunt infection, were evaluated in those patientswith follow-up periods greater than 6 months.

RESULTS: A total of 153 pediatric patients (age range, 1–21 yr)underwent 262 shunting procedures involving use of antibiotic-impregnated catheters. All patients were followed for longer than 6months with a mean follow-up period of 15.7 months (range, 7–40mo). Ten patients (3.82%) experienced an early shunt infection withinthe 6-month follow-up period. No patients experienced a late shuntinfection.

CONCLUSION: AIS catheters do not lead to a significantly in-creased incidence of late cerebrospinal fluid shunt infection in chil-dren with hydrocephalus compared with historic controls.

874Noninvasive Measurement of Intracranial Pressureand Cerebral Blood Flow in Patients withHydrocephalus: 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 hydro-cephalic patients with symptoms suggesting raised intracranial pres-sure (ICP) is challenging because ventricle size often lacks the speci-



ficity to predict abnormal ICP. An early assessment of the potentialclinical utility of a noninvasive magnetic resonance imaging (MRI)-based measurement of intracranial pressure (MR-ICP) in symptomatichydrocephalic 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 cerebralblood flows to and from the cranial vault from which measurementsof ICP and cerebral blood flow were derived using a previouslydescribed algorithm. The predictive values of the MR-ICP measure-ment were determined based on whether or not the patient underwenta surgical treatment of a shunt placement or shunt revision within a3-month period following the MRI study.

RESULTS: MR-ICP values in these patients spanned a much widerrange 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, butspanned a much wider range.

CONCLUSION: The short-term follow-up of patients who hadnormal MR-ICP measurement reveals that only one of the 20 requiredsurgery. Consequently, the MR-ICP measurement has a strong nega-tive predictive value (95% for all patients and 100% for patientswithout a shunt).

875Pediatric Infratentorial Subdural Empyemas:A Series of 14 PatientsParitosh P. Pandey, M.B.B.S., M.C.H.

INTRODUCTION: Infratentorial empyemas are rare lesions, form-ing only 0.6% of all cases of intracranial suppurative disorders. Pos-terior fossa empyemas are associated with high morbidity and mor-tality despite prompt and aggressive treatment.

METHODS: A series of 14 children (age � 18 yr ) over a period of10 years (1995–2005) were analyzed retrospectively.

RESULTS: This condition was predominantly found in males (64%)and in the summer months. The source of infection was middle earinfection in 92.9%. Clinical features were a combination of headache,fever, vomiting, and meningism in a setting of ear discharge. Cere-bellar signs were found in only 21% of patients; 85.7% of patients werein altered sensorium with Glasgow Coma Scale scores between 11 and14. In 79.6% of patients, pus collection was seen over the cerebellarconvexity. Other sites were tentorial (28.6%) and the cerebellopontineAngle (21.4%). All patients were started on antibiotics. All patientswere operated on (burr holes in 21%, craniectomy in 79%). Fourpatients required repeat surgery for residual empyemas. Hydroceph-alus was seen in 92.9% of the patients. Five patients needed externalventricular drainage during surgery or postoperatively and two re-quired shunt for persistent ventriculomegaly. The pus culture posi-tivity rate was 71.4%, and 21% of patients had polymicrobial infection.Three patients developed minor postoperative complications. Therewas no mortality in the series. Follow-up data was available for nineout of 14 patients. Glasgow Outcome Scale scores at the time offollow-up were good, with scores of 5 or 4 in all patients.

CONCLUSION: Posterior fossa empyemas present with a nonspe-cific constellation of symptoms. Cerebellar signs are seen in only aminority. Surgery and antibiotics are the mainstays of treatment.Hydrocephalus may be managed with external ventricular drainageand a permanent shunt is needed in only a small percentage of

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

876Recurrence of Synostosis after Surgical Repair ofCraniosynostosisKimberly A. Foster, B.A., McKay McKinnon, M.D.,David M. Frim, M.D.

INTRODUCTION: Incidence of resynostosis in patients havingundergone surgical release of a synostotic suture is not well reported.This study examines cases of non-syndromic and syndomic cranio-synostosis having undergone surgical repair and establishes the rateof reoperation for synostosis in the series.

METHODS: Charts were retrieved from 119 consecutive patientstreated for craniosynostosis at our institution (62% male; 11% treatedfor craniofacial dysostosis; Apert syndrome, n � 2; Crouzon syn-drome, n � 4; Saethre-Chotzen, n � 5; other, n � 2).

RESULTS: Eight (6.7%) patients underwent operation for resynos-tosis (nonsyndromic, 6 out of 106, 5.7%; syndromic, two out of 13,15.4%). Seventy-nine (66.4%) patients underwent primary surgery atyounger than 1 year of age. Analysis by age at primary operationyielded significant resynostosis rates (P � 0.02) when patientsyounger than 1 year of age (n � 2, 2.5%) are compared with thoseolder than 1 year of age (n � 6, 15%). Further stratifications of age atinitial reoperation did not yield significance for resynostosis. Caseswith documented raised intracranial pressure preoperatively (n � 9,7.6% of total population) are noted to have an increased rate ofresynostosis (n � 4, 44.4%, P � 0.001). A trend of increasing meanlength of hospital stay, estimated blood loss, and operative time in thepatients who eventually resynostosed is observed, but the data werenot significant.

CONCLUSION: Resynostosis rates were higher in syndromic chil-dren than in nonsyndromic cases in which a single suture was in-volved. Analysis of age at primary operation shows an increase inresynostosis if primary operation occurs after the age of 1 year. Inaddition, evidence of raised intracranial pressure at primary operationmay predispose to recurrence of craniosynostosis.

877Psychobehavioral Effects of Chronic SubthalamicStimulation and the Topography of SubthalamicNucleusSheng-Tzung Tsai, M.D., Shin-Yuan Chen, M.D.

INTRODUCTION: Psychobehavioral effects of chronic subthalamicstimulation (STN-DBS) in Parkinson’s disease (PD) are variable.Whether these side effects resulted from target per se or currentdiffusion into neighboring structures was uncertain. The relationshipbetween the clinical outcome and the active electrode contact wasanalyzed and was compared between the patients with and withoutpsychobehavioral consequence.

METHODS: Thirty-eight consecutive PD patients who underwentbilateral STN-DBS were enrolled in this retrospective cohort study. Atthe time of follow-up, they were divided into two groups for compar-ison: Group A (with psychobehavioral side effect) and Group B (with-out psychobehavioral side effect). The position of the active contact ofthe electrode was defined with postoperative magnetic resonance



imaging scans. The active contact coordinates and the clinical out-comes were compared between the two groups.

RESULTS: Among these 38 PD who underwent STN-DBS, eightpatients who had psychobehavioral side effects were assigned toGroup A; the other 30 patients were assigned to Group B. In GroupsA and B, the mean follow-up period was 13.9 and 7.1 months, respec-tiveley, 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 and46.4%, respectively (P � 0.16). The mean coordinates of the activecontact in both groups were x � 10.1 and 10.5 mm, y � �2.8 and �3.9mm, and z � �6.3 and �6.2 mm, respectively. A significant differencewas observed on the y axis (P � 0.01). When we compared thecoordinates between the groups side by side, a significant differencewas observed on the y axis of left side (P � 0.007; odds ratio, 12.0).

CONCLUSION: The psychobehavioral effects of chronic STN-DBSwere significant related to an anteriorly located electrode in the leftSTN, despite a prominent improvement in the motor symptoms. Theposterior lateral portion of the STN will be an optimal area to place theelectrode without causing psychobehavioral side effects duringchronic stimulation.

878Cortical Stimulation for Motor Recovery after Stroke:Impact on Neuropsychological Performance andFunctional 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 cog-nitive deficits commonly result from stroke. We tested the hypothesesthat cortical stimulation (CS) combined with intense rehabilitationtherapy could stimulate functionally significant neuroplasticity evi-dent on functional imaging, enhance motor recovery, and improvedeficits in neurocognitive function after stroke.

METHODS: Two randomized prospective studies were conducted ateight clinical sites. Functional magnetic resonance imaging scans bothbefore and after therapy was used to define the cortical hand region.Thirty-two patients with hand/arm weakness from ischemic stroke of 4or more months earlier were randomized to an investigational epiduralgrid electrode over hand motor cortex and pulse generator that deliveredCS during rehabilitation (investigational group) or rehabilitation alone(control group). Motor function was assessed using the Upper ExtremityFugl-Meyer (UEFM) scale. A neuropsychological test battery was admin-istered before and after therapy.

RESULTS: The investigational group showed greater improvementsin motor function compared with controls at 4 weeks (UEFM, 6.4 versus1.9 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 clinicallymeaningful motor function improvements (4 wk: 71 versus 31%, P �0.01; 12 wk: 81 versus 38%, P � 0.01). Investigational patients withleft-sided stroke demonstrated more language improvement than con-trols, as measured by the Wechsler Abbreviated Scale of Intelligencevocabulary t-score (1.3 versus -3.8 points; P � 0.05). A trend for greatergains in confrontation naming (in left-sided stroke patients) and onvisuospatial abstraction (in right-sided stroke subjects) was also observedfor investigational patients. Activation site variability was substantial (12,23, and 11 mm in x, y, and z directions, respectively), exceeding electrode

dimensions. A reduction in brain activation volume was observed only ininvestigational patients.

CONCLUSION: CS improves hand/arm function over intensiverehabilitation alone; this correlates with consolidation of brain activa-tion on functional magnetic resonance imaging scans. CS may alsoimprove neurocognitive function after stroke.

879Therapeutic 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 humannuclear transfer in humans, cloning of somatic cells in vertebrates iswell-described and reproducible.

METHODS: We obtained tail cells from a group of five mice andtransferred the nuclei by microinjection into enucleated oocytes obtainedfrom donor mice. The oocytes developed into blastocysts and embryonicstem (ES) cell lines were derived. The ES lines, now carrying the geno-type of the tail cell donor, were subjected to a neural induction protocoland differentiated into dopamine neurons following our previously de-scribed methods. The tail donor mice were rendered Parkinsonian byintrastriatal injection of 6-hydroxydopamine and their behavior abnor-malities were subsequently quantified. The dopamine neurons obtainedfrom the tails were injected in the striatum of the corresponding lesioneddonor animal and the rotational behavior measured over 3 months.

RESULTS: Our data demonstrates graft survival, maintenance ofdopaminergic phenotype, and behavioral improvement of the Parkin-sonian animals. The efficiency of generation of ES lines from clonedblastocysts will be discussed.

CONCLUSION: This is the first demonstration that “cloning” can beused therapeutically. We were able to derive for each Parkinsoniananimal its own autologous dopamine neurons starting with a tail biopsy.The nuclei of the tail cells were transferred into enucleated oocytes andES lines were successfully generated. The ES lines offer an enormouspotential 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.

880Pediatric Language Mapping: Sensitivity ofNeurostimulation 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 withelectrical neurostimulation was utilized both intra- and extraopera-tively to tailor resections. In pediatric patients, functional mappingstudies frequently fail to localize language, and Wada testing has alsobeen reported to be less sensitive in children.

METHODS: Thirty children (4.7–14.9 yr) and 18 adult controls(18–59 yr) who underwent extraoperative language mapping via im-planted subdural electrodes at the New York University Comprehen-sive Epilepsy Center were included in the study. Ten children and 14adults underwent preoperative Wada testing. Success of the proce-dures was defined as the identification of at least one language site by



neurostimulation mapping and determination of hemispheric lan-guage dominance on the Wada test.

RESULTS: In children under the age of 10.2 years, cortical stimulationfailed to identify language cortex at a higher rate than was seen inchildren over the age of 10.2 years and in adults (P � 0.05). This thresh-old, demonstrated by survival and x2 analysis, was sharply defined inour data set. Additionally, Wada testing was more likely to be successfulthan extraoperative mapping in this younger age group (P � 0.05).

CONCLUSION: Analysis of our series demonstrated that languagecortex was less likely to be identified in children younger than 10years of age, suggesting that alternatives to the currently used meth-ods of cortical electrical stimulation, particularly the use of preoper-ative language lateralization, may be required in this age group.

881Initial Surgical Experience with an IntracorticalMicroelectrode Array for Brain-computer InterfaceApplicationsGerhard 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 a4 x 4 mm 96-channel intracortical microelectrode array, which is beingtested in a pilot safety and feasibility trial for the development ofbrain-computer interfaces for people with paralysis.

METHODS: The BrainGate Neural Interface System includes animplantable sensor (a microelectrode array) with a percutaneous ped-estal and external components for signal processing, signal decoding,and external device control. The array consists of 100 1 to 1.5 mmsilicon probes, 96 of which are active electrodes. Using a pneumaticinserter, the array is implanted into the precentral “knob” (armand/or hand area), as identified by preoperative magnetic resonanceimaging scans. The pedestal is secured to the cranium and external-ized percutanteously, allowing a cable to connect to external compo-nents. After allowing for wound healing (approximately 2 wk), neuralrecordings are obtained at least weekly. Participants were asked toimagine limb movements and attempts were made to decode thereal-time neural activity into a useful control signal for an externaldevice (e.g., a computer cursor). Patients aged 18–70 with spinal cordinjury, brainstem stroke, or muscular dystrophy with limited use oftheir arms and/or hands were eligible for our ongoing study.

RESULTS: We report on two patients with spinal cord injury whoexperienced array implantation. Surgical time was less than 3 hours inboth cases. Patients were discharged from the hospital after 2 to 3days. No surgical infections occurred, and there were no unantici-pated adverse device effects. Recordings demonstrate the presence ofneurons and the patient’s ability to modulate the recorded activitywith movement intention. Recordings began in the second patientafter a defect in the pedestal was repaired. The array was removed inPatient 1 at the end of the planned trial period of 1 year. Arrayremoval was straightforward. No grossly notable tissue reaction wasnoted except for a slight indentation of the cortex. The superficialaspect of the array seemed secured by an arachnoid-like membrane.Postoperative recovery was uneventful.

CONCLUSION: Our preliminary experience indicates that a smallarray of microelectrodes can be successfully implanted and removedfrom the human motor cortex. This array may provide a useful sensor

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

882Tailored Temporal Lobectomy for MedicallyIntractable Epilepsy: Long-term Outcomes in a Seriesof 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 electroco-chleography, neuropsychological, and other data to limit the amountof resection performed in temporal lobe epilepsy cases. Because lesstemporal 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 fora review of Engel’s Class outcomes in a series of patients undergoingtemporal lobe epilepsy surgery during a 6-year period. Standard demo-graphic data, epilepsy risk factors, side of surgery, extent of resection onthe lateral cortex, extent of hippocampal resection, and pathology wereevaluated as independent predictors of seizure outcome.

RESULTS: One hundred and forty consecutive patients had at least2-year follow-up and met the criteria for the study. Eighty four pa-tients had mesial temporal sclerosis, and 29 patients had low-gradeglioma. Seventy-nine percent of patients were Engel’s Class I (a-d) atlast follow-up. The complication rate was 2.8% (dysphasia, 2; woundinfection, 2). Abnormal magnetic resonance imagining findings ofmesial temporal sclerosis or tumor was the only factor significantlycorrelated with Engel Class I outcome (P � 0.01). Greater extent oflateral resection (P � 0.1) and fewer preoperative seizures bothshowed a trend towards better seizure outcome that did not reachstatistical significance (P � 0.1). Extent of hippocampal resection didnot correlate with seizure outcome (P � 1.0). In a subclass of 39patients with pre- and postoperative Wechsler neuropsychologicaltesting, extent of hippocampal resection did not correlate with imme-diate or delayed memory scores (P � 1.0, P � 0.4).

CONCLUSION: In temporal lobe epilepsy, excellent post surgicaloutcomes are achievable with very low morbidity using the tailoredtechnique. As in most series, the outcome is influenced by pathology.At a minimum of 2 years follow-up, cases where the extent of resec-tion of the hippocampus was limited to the anterior 2.5 cm had similaroutcomes to cases where a full hippocampal resection was performed.

883Lentiviral Delivery of Glial Cell Line-derivedNeurotrophic Factor in Aged 1-methyl-4-phenyl-1,2,3,6-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 beenidentified as risk factors for sporadic Parkinson’s disease. In thisstudy, we assess the potential for functional recovery induced by glialcell line-derived neurotrophic factor (GDNF ) in a diseased and agedprimate brain.



METHODS: Male rhesus monkeys, aged 24 to 30 years, received asingle intracarotid infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which resulted in unilateral parkinsonism. Itwas followed 1 week later by magnetic resonance imaging-guided ste-reotaxic intrastriatal and intranigral injections of lentiviral vectors encod-ing for GDNF (lenti-GDNF, n � 5) or lacZ (lenti-LacZ, n � 4).

RESULTS: Lenti-GDNF treated monkeys had a significant im-provement in the clinical rating compared with lenti-LacZ starting at5 weeks after surgery that persisted until necropsy. The fine motorskills on a timed “pick-up test” slowly improved in the lenti-GDNFtreated monkeys while lenti-LacZ animals had extreme difficulties orwere unable to complete the task. Positron emission tomographyscans performed 12 weeks after surgery (before necropsy) revealedincrease fluorodopa uptake in the caudate and putamen ipsilateral tolenti-GDNF treatment compared with lenti-LacZ that correlated withthe clinical rating score. GDNF enzyme-linked immunosorbent assayof striatal brain samples confirmed high GDNF expression in lenti-GDNF treated monkeys. The high levels were associated with in-creased F-Dopa uptake and behavioral improvement. Immunohisto-chemistry revealed: 1) GDNF and LacZ gene expression 3 monthsafter surgery in the target areas; 2) increased dopaminergic markersimmunoreactivity (tyrosine hydroxylase and VMAT2) associated withareas of GDNF expression; 3) minimal micro- and astrogliosis asobserved with CD68 and glial fibrillary acidic protein specific anti-bodies.

CONCLUSION: Our results indicate that the aged primate brainexposed to a neurotoxic insult is responsive to GDNF neuroprotectivetrophic stimulation locally delivered by lentiviral vectors.

884Safety and Preliminary Efficacy of a ResponsiveNeurostimulator for the Treatment of IntractableEpilepsy in AdultsRobert 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 assessedsafety and possible efficacy of the cranially based implantable, pro-grammable Responsive Neurostimulator (RNS) system.

METHODS: Patients were 18 to 65 years old with intractablepartial-onset seizures and localized epileptogenic onset region(s). Pa-tients with more than 12 simple partial (SP) sensory or motor seizures,complex partial seizures (CPS), or generalized tonic-clonic (GTC) sei-zures during an 84-day baseline period qualified for implant. The RNSwas connected to up to 2 leads (subdural and/or depth), which weretargeted to the seizure focus. Adverse events were monitoredthroughout the trial. Efficacy was assessed during 2 time periods: the84-day period beginning 28 days postimplant (primary) and the mostrecent 84 days for which a patient could have received therapy (sec-ondary).

RESULTS: During the primary evaluation period, the responderrate (� 50% reduction in seizures) in 48 patients (excluding 8 patientsblinded off) was 32% for CPS, 63% for GTC, and 27% for totaldisabling seizures (TDS) (SP motor, CPS, and GTC). The medianpercentage reduction in seizure frequency was CPS 27%, GTC 59%,and TDS 29%. Seizure reduction was significant for CPS (P � 0.05) and

TDS (P � 0.001) (Wilcoxon signed-rank test). For the secondary eval-uation period, the responder rate for 56 patients was 36% for CPS, 50%for GTC, and 36% for TDS. The median percentage reduction was CPS28%, GTC 50%, and TDS 30%. Seizure reduction was significant forCPS (P � 0.005), GTC (P � 0.02), and TDS (P � 0.001). In 65 implantedpatients, including 17 device replacements, there were no seriousunanticipated device-related adverse events. Responsive neurostimu-lation was well tolerated. Results are current as of March 10, 2006.

CONCLUSION: An investigation of responsive stimulation usingthe RNS system demonstrated excellent safety and a significant andsustained reduction in CPS, GTC, and TDS events. Preliminary resultsindicated that the RNS system may provide a safe and effectivetreatment for adults with intractable partial-onset epilepsy.

885A Prospective Randomized Double-blind Trial ofBilateral Thalamic Deep Brain Stimulation in Adultswith Tourette SyndromeRobert 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 per-sists into adulthood is a devastating disease with limited therapeutic options.We conducted a prospective, double-blind crossover trial of bilateral tha-lamic deep brain stimulation in five adults with TS.

METHODS: Patients were screened by a neurologist, psychiatrist,neurosurgeon, and neuropsychologist. Baseline studies includedvideo recording and administration of standard instruments, includ-ing Yale Global Tourette Severity Scale (YGTSS), Tourette SyndromeSymptom List (TSSL), Short-Form 36 (SF-36), and a quality of lifeVisual Analog Scale (VAS). Bilateral thalamic electrodes were im-planted at targets suggested in a previously published report. Afterrandom double-blind activation of unilateral or bilateral stimulation,subjects were assessed with video recording, YGTSS, and TSSL. Threemonths after unblinded bilateral stimulator activation, the same stud-ies were repeated, as well as SF-36, quality of life VAS, and neuro-psychological measures.

RESULTS: In the randomized phase of the trial, a statisticallysignificant (P � 0.03, Friedman’s exact test) reduction of score on themodified 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 theYGTSS and TSSL scores, was also noted. Benefit was persistent at 3months after conclusion of the double-blind randomized portion ofthe trial. Quality of life indices were improved.

CONCLUSION: By all criteria, as measured by primary and sec-ondary outcome variables, three of five patients (60%) were signifi-cantly improved. Bilateral thalamic deep brain stimulation seems toreduce tic frequency and severity in patients with TS.

886Late Seizures in Patients Initially Seizure-free afterEpilepsy SurgeryTheodore 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 iscurrently the most effective means of achieving seizure control. Al-



though there are relatively few long-term outcome studies, evidence ismounting that the possibility of late seizure recurrence exists evenafter an early seizure-free period. No published reports document therate and predictors of late recurrence in a large series of patientsundergoing surgery since the advent of magnetic resonace imaging(MRI) scanning.

METHODS: We retrospectively queried the databases of twoepilepsy surgery centers. Patients eligible for study had preopera-tive MRI scans, were seizure free for 1 year after surgery, and hada minimum follow-up period of 3 years. Patients with tumors orvascular lesions were excluded. We performed log-rank compari-son of Kaplan-Meier product limit estimates for categorical vari-ables and used a Cox proportional hazards model for continuousvariables. Variables that were significant (P � 0.05) on a univariatescreen were entered into a multivariate forward stepwise Coxregression.

RESULTS: The study included 285 patients, 254 with medial tem-poral lobe, and 31 with neocortical epilepsy. The probability of havinga single seizure after being seizure-free for 1 year was 18.3% at 5 yearsand 32.7% at 10 years. However, only 13% were not seizure-free at thelast follow-up. Predictors of late recurrences on both uni- and multi-variate analysis were the presence of preoperative generalized tonicseizures in patients with neocortical epilepsy and late age at surgeryin patients with medial temporal lobe. MRI scan results and locationof surgery were not predictive.

CONCLUSION: Although the risk of at least one recurrent seizureafter initially successful epilepsy surgery is relatively high, the rate ofrecurrent intractability is low. The finding that late age at surgery andpresence of preoperative generalized tonic seizures are predictors oflate recurrence indicates the importance of patient selection and earlysurgery for persistent seizure control.

887Grafts of Neural Precursors Derived from the BasalForebrain Improve Motor Function in ExperimentalStrokeMarcel 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 thedeveloping basal forebrain is the host of neural precursors with stemcell characteristics. The MGE give rise to specific populations ofneuronal precursors that repopulate the developing striatum andcortex. Furthermore, when grafted into the adult rat striatum, theMGE-derived neuronal precursors integrate, mature, and form syn-apses with host cells. In the present study, we asked the questionwhether or not MGE-derived neuronal precursors are an efficacioussource of neurons for cellular therapy in the rat model of ischemicstroke.

METHODS: The MGE cells were derived from transgenic rat em-bryos carrying the enhanced green fluorescent protein-encoding gene.Adult rats were subjected to one and one-half hour suture occlusion ofthe middle cerebral artery. Two weeks after the lesion, 2 �l of MGEcell suspension at a concentration of 50,000 cell/�l was stereotaxicallytransplanted into four sites within the lesioned striatum and cortex.As group controls, we used rats subjected to ischemia and trans-planted either with fibroblasts or with the vehicle. All animals under-went baseline motor behavioral assessment before and after ischemiclesion and cell transplantation.

RESULTS: Our data demonstrate that one month after cell trans-plantation, the MGE-grafted animals significantly improved their mo-tor behavioral deficits compared with the fibroblast and vehicle con-trol groups, as assessed using the rotarod (P � 0.05) and the elevatedbody swing tests (P � 0.05). Immunocytochemical analysis of the graftdemonstrated a 16.4% survival rate. The transplanted MGE cells ex-pressed NeuN and TuJ1 neuronal markers and the synaptic markersynaptophysin indicating innervation of the host cells. In additionthere was a fourfold increase in synaptophysin expression in the MGEtransplant area (P � 0.001) compared with control animals.

CONCLUSION: These data suggest that the MGE-derived neuro-nal precursors may be a promising cell type for cellular therapy instroke.

888A Multitarget GABA-ergic Basal GangliaTransplantation Strategy Enhances ComplexSensorimotor Behavioral Recovery inHemiparkinsonian RodentsKarim Mukhida, M.D., Murray Hong, Ph.D.,Ivar Mendez, M.D., Ph.D.

INTRODUCTION: The current transplantation strategy for Parkin-son’s disease that places fetal dopaminergic grafts in the striatum (ST)fails to reconstruct basal ganglia circuitry and is limited by the lack ofstandardized clinical grade cells. It was hypothesized that to producecomplete restoration of parkinsonian behavioural deficits, inhibitionof the subthalamic nucleus (STN) and substantia nigra (SN) byGABAergic transplants is needed in addition to reconstruction ofnigrostriatal circuitry via dopaminergic transplants, and that humanneural precursor cells (NPCs) can be used as an alternative to fetaltissue as a standardized source of clinical grade cells for basal gangliatransplants.

METHODS: Human fetal telencephalon-derived NPCs were pred-ifferentiated into a GABAergic phenotype in vitro and theirelectrophysiological characteristics were determined. These cellswere transplanted into the STN, SN, or both sites in conjunctionwith dopaminergic grafts of the ST of rats with unilateral6-hydroxydopamine lesions. Control animals received dopaminergicgrafts alone or in conjunction with undifferentiated NPCs or fetalGABAergic cells derived from the embryonic rat striatal primordia.Complex sensorimotor behavioural recovery was assessed pre- andpostlesion and posttransplantation. Ten weeks posttransplantation,graft function and viability was assessed electrophysiologically andimmunohistochemically.

RESULTS: By 9 weeks posttransplantation, animals that receivedGABAergic grafts showed significant improvement in lesion-inducedbehaviours (akinesia, spontaneous forelimb use, and motor function[P � 0.05]) compared with control animals. Electrophysiology dem-onstrated functioning potassium channels in GABAergic NPCs. Con-focal microscopy showed that predifferentiated NPCs maintained aGABAergic and neuronal phenotype in vivo. In contrast, undifferen-tiated cell transplants differentiated exclusively into astrocytes.

CONCLUSION: Restoration of dopaminergic activity to the ST inconcert with inhibition of the SN and STN by GABAergic graftspromotes a more complete functional recovery of complex sensorimo-tor behaviors and may be crucial in improving clinical outcomes inpatients with Parkinson’s disease. Potential clinical application of thisstrategy may be enhanced by predifferentiated bioreactor-expandedNPCs.



889Continuous Intrathecal Baclofen Infusion in theTreatment of Spastic Cerebral Palsy: A ProspectiveMulticenter StudyYves R. Lazorthes, M.D.

INTRODUCTION: The purpose was to assess the benefits ofContinuous Intrathecal Baclofen Infusion in children with cerebralpalsy, not only on spasticity, but also on motor and functionalperformances.

METHODS: Twenty-four patients with severe diffuse spasticitywere selected in 11 French centers, using a multidisciplinary ap-proach (age, 6–8 yr; mean Ashworth score 3 in the lower limbs,failure of oral baclofen). A double-blind screening was performedin all patients with i-Th bolus (starting from 12.5 and increasing to100 mcg baclofen) until a positive response for lower limbs. Fol-lowing a succesful trial, patients were considered for implantation(Synchromed system; Medtronic, Inc., Minneapolis, MN). Assess-ment during a 2-year peroid included spasticity scoring, quantita-tive functional evaluation (Gross Motor Function Measure scale)and a qualitive questionnaire.

RESULTS: Trial procedures resulted in a significant average dropin Ashworth scores in the lower limbs from 3.7 to 1.8 points (averagedose, 44 �g baclofen). Despite good clinical effects on spasticity, fivepatients were not implanted. Seventeen patients were followed for 2years. Effects on lower limbs spasticity remained stable, as was thecase in upper limbs (2.4 and 1.7, respective average score) as dailyaverage dose increased from 124 to 185 �g. Average GMFM scoresremained stable throughout the study, and qualitative evaluationsindicated that pain was reduced and ease of mobility and sleepimproved. Patients and families expressed a high level of satisfactionComplications occured in 10 patients, mostly in the first months, noneleading to any pump explant.

CONCLUSION: Results confirms the efficacy of Continuous Intra-thecal Baclofen Infusion in reducing severe spasticity in children withcerebral palsy and its clear benefits in patients care and comfort.

890Deep Brain Stimulation for the Enhancement ofLearningEmad 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 gan-glia play a critical role in learning. The neostriatum receives projec-tions from virtually all areas of the cortex and is characterized by astrong dopaminergic input from the midbrain. Dopaminergic neuronsseem to convey a feedback signal regarding the profitability of certainactions. In vitro studies have demonstrated that phasic dopaminerelease can cause potentiation of corticalstriatal synapses. In addition,there is evidence that disruption of basal ganglia circuitry result inproblems with learning.

METHODS: There are currently no surgical techniques to enhancelearning in patients with traumatic brain injuries, strokes, or severelearning disabilities. We used high-frequency microstimulation andfixed-potential amperometry within the anterior striatum of primatesactively performing an associative learning task to evaluate whetheror not it is possible to modulate learning behavior.

RESULTS: We found that high-frequency stimulation in thecaudate resulted in a significant enhancement in the rate of learn-ing of specific associations (t test, P � 0.001). We then used theelectrochemical technique of amperometry and found that high-frequency microstimulation results in a significant release of do-pamine within the anterior striatum. These data suggest that theeffects of striatal microstimulation are mediated through induceddopamine release.

CONCLUSION: Deep brain stimulation is widely used for thetreatment of Parkinson’s disease, dystonia, tremor, and other disor-ders. Hence, it is quite feasible to use a similar technique to treatdisorders wherein patients exhibit significant learning deficits. Thecurrent data suggest that this is feasible. Further studies will beneeded to assess the best parameters for stimulation, to ascertainwhether cortical stimulation is as effective as striatal stimulation, andto determine whether continuous stimulation is as effective as inter-mittent stimulation.

891Dynamic Encoding of Reward Prediction andMovement in the Subthalamic Nucleus of Patientswith Parkinson’s Disease and Normal MonkeyFelipe A. Jain, B.S., Emad N. Eskandar, M.D.

INTRODUCTION: Increasing data indicate that the basal gangliaserve to dynamically and selectively facilitate biologically profitableor rewarding movements. However, the way in which basal ganglianeurons encodes reward information remains opaque. We hypothe-sized that the subthalamic nucleus (STN) might increase directionalselectivity based on the expectation of rewarded versus unrewardedmovements.

METHODS: Patients with Parkinson’s disease undergoing thera-peutic deep brain stimulation electrode implantation were asked toparticipate in the study. During microelectrode recordings, patientsperformed movements with different expectations of monetary re-ward. A nonhuman primate performed an identical task but withreceipt of a juice reward.

RESULTS: We obtained data from 21 neurons in three patientsundergoing surgery, and 32 neurons from one monkey. In humansduring cue presentation, 52% of neurons showed changes in meanfiring based on direction (P � 0.01) from unrewarded to rewardedconditions, as did 41% of neurons in the monkey. In humans, theexpectation of reward had a significant effect on directional tuning ofthe population of cells, reversing the preferred direction (P � 0.001).In contrast, the normal nonhuman primates did not significantlychange directional selectivity as a population. During movement,irrespective of reward status, the majority of neurons exhibited anincrease in activity that averaged 180% during the movement period(P � 0.001), whereas the normal monkey STN neuronal firing ratestended to decrease (P � 0.1) during movement.

CONCLUSION: The STN in both humans and normal monkeyencodes predictive information about the receipt of reward. In hu-mans, the expectation of reward seems to markedly modify the direc-tional tuning of the population of cells, whereas in the normal state,expectation of reward has a modest effect on the responses. In theparkinsonian state, STN neurons may dynamically inhibit movementby increasing firing, whereas in the normal state, the STN tends todecrease activity, possibly representing movement facilitation.



892Endoscopic, Endonasal Extended TranssphenoidalTransplanum Transtuburculum Approach forResection of Suprasellar LesionsTheodore H. Schwartz, M.D., F.A.C.S., Vijay K. Anand, M.D.

INTRODUCTION: The extended transsphenoidal approach is aless invasive method for removing purely suprasellar lesions com-pared with traditional transcranial approaches. Most advocates haveused a sublabial incision, a microscope, and report a significant risk ofcerebrospinal fluid (CSF) leak. We report a series of purely endoscopicendonasal surgeries for resection of suprasellar, supradiaphragmaticlesions above a normal-sized sella.

METHODS: A purely endoscopic endonasal approach was used toremove suprasellar lesions in a series of 10 patients. Five lesions wereprechiasmal (tuburculum sellae and planum meningiomas) and fivewere retrochiasmal (4 cranipharyngiomas, 1 Rathke’s cyst). The floorof the planum and the sella was reconstructed using a multilayerclosure with autologous and synthetic materials. Spinal drainage wasused in five of the cases.

RESULTS: Complete resection of the lesions was obtained in all butone patient. The pituitary stalk was preserved in all but one patientwhose stalk was invaded by a craniopharyngioma and who hadpreoperative diabetes insipidus. Vision improved postoperatively inall patients who had preoperative vision impairment. Six patients hadtemporary DI, and five developed permanent diabetes insipidus. Fourpatients with craniopharyngiomas required cortisone and thyroidreplacement. There was one transient CSF leak when a lumbar drainwas clamped prematurely.

CONCLUSION: A purely endoscopic endonasal approach to su-prasellar, supradiaphragmatic lesions is a feasible minimally invasivealternative to craniotomy. With a multilayer closure, the risk of CSFleak is low and lumbar drainage can be avoided. A larger series willbe required to validate this approach.

893A Small Interfering Ribonucleic Acid-basedApproach to Characterize Brain Tumor Resistance toRadiation TherapyClark C. Chen, M.D., Ph.D., Richard Kennedy, M.D.,Alan D’Andrea, M.D.

INTRODUCTION: The use of radiation therapy in brain tumortreatment has led to improvements in patient survival. However,tumor recurrence from resistance to radiation remains a therapeuticchallenge. To address this challenge, we conducted a large-scale smallinterfering ribonucleic acid (SiRNA) screen to identify genes requiredfor tumor resistance to radiation.

METHODS: SiRNA is an experimental tool that can be used toinhibit the protein expression of a target gene. This technology wasapplied in a large-scale screen to identify genes in the U87 glioma cellline that are required for radiation resistance. U87 cells were platedinto 96 well plates, and each well was transfected with SiRNAsdirected against different deoxyribonucleic acid repair genes. In total,712 distinct SiRNA were tested in triplicates. Two days after transfec-tion, the cells were irradiated (10 Gy). Subsequently, cell survival wasdetermined using the Promega Luminescent viability assay. Ourstudy revealed 13 genes that when silenced by SiRNA caused signif-icant radiation sensitivity. The importance of these genes in radiationresistance was confirmed using clongenic survival assays. Gene si-

lencing was verified using Western blotting and/or quantitative poly-merase chain reaction. “Off-target” effects were excluded using mul-tiple SiRNAs against each candidate gene.

RESULTS: Our analysis revealed that genes known to conferradiation-resistance in cell lines such as Hela, 293T, or primary fibro-blasts (ATR, RPA, Histone DeACetylase2 [HDAC2], WEE1, RAD17,RAD9A) are also active in the U87 cell line. Additionally, novelradiation resistance genes not previously reported to influence radi-ation sensitivity (CDK7, CCNH, KDEL2, MIA, FAP, KIA0101) wereidentified.

CONCLUSION: This study represents the first SiRNA-based ap-proach to identify the genes required for radiation resistance in glio-mas. Our results suggest that deoxyribonucleic acid repair pathwaysuncovered in other experimental systems also operate in the U87glioma cell line. Pharmacologic inhibition of these pathways or thenovel genes uncovered in this study represent potential strategies forcancer treatment.

894A Phase I Trial of Intracranial Dendritic CellImmunotherapy for Patients with Malignant GliomaJohn 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 in-oculation of freshly cultured, immature dendritic cells (DCs) into anintracranial tumor results in the generation of a potent antitumorimmune response as evidenced by prolonged survival and immunityto tumor rechallenge.

METHODS: In this Phase I trial, 23 patients with recurrent malig-nant glioma (three patients with anaplastic astrocytom and 20 patientswith glioblastoma multiforme) with areas of gadolinium enhancementless than or equal to 3 cm in eloquent regions of the brain underwentstereotactic radiotherapy (25 Gy in 5 Gy fractions over 2 wk). Within2 weeks, these patients underwent subtotal surgical resection andplacement of dendritic cells in an area of gadolinium enhancementwith guidance from stereotactic navigation. This was a dose-escalationstudy of intracranial dendritic cell injections. Injection doses wereescalated in six cohort groups of three patients starting at 500,000 cellsand five patients at the highest dose of 128 million cells. Stereotacticradiotherapy was followed by intracranial injection of autologousdendritic cells, which had been harvested from peripheral blood pre-cursors 1 week prior.

RESULTS: There were no common toxicity criteria Grade III/IVtoxicities noted that were associated with trial-related procedures.There were no dose limiting toxicities up to 128 million cells. Two outof seven patients who were tested demonstrated a positive cytotoxic Tlyphocyte response after intracranial DC administration based on aquantitative polymerase chain reaction assay for IFN-� expression. Ofthe 20 recurrent glioblastoma patients, survival spanned from 9.6 to132 weeks from the time of their immunotherapy treatment, with amedian survival of 48 weeks. Six patients are living, including the firstpatient treated. Six patients underwent reresection after tumor recur-rence following their immunotherapy. One patient demonstrated aprominent lymphoid infiltrate consisting predominantly of cytotoxicT-cells (CD3�, CD8�, CD45RO�) and scattered helper T-cells andB-cells (CD4�, CD20�).

CONCLUSION: These data demonstrate that intratumoral place-



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

895Chimeric T-cell Receptor Therapy for GlioblastomaMultiformeSzofia 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 TypeIII (EGFRvIII) is self-dimerizing, oncogenic, tumor-specific receptorthat is highly expressed in glioblastoma multiforme. We describe aclinically viable protocol for the genetic engineering of human T-cellsto attack glioma cells expressing EGFRvIII though the use of chimericT-cell receptor technology.

METHODS: The chimeric immune receptor fusion protein (MR1-CIR) is composed of two functional entities: MR1, a single chainantibody that specifically binds EGFRvIII, and the human zeta chainof the T-cell receptor that permits major histocompatibility complexindependent signaling of the cytotoxic cascade in T-cells that engageEGFRvIII expressing cells. Human peripheral blood mononuclearcells were transfected with MR1-CIR, selected on hygromycin, andexpanded to clinically relevant numbers. Stable expression of theMR1-CIR was confirmed by reverse transcription polymerase chainreaction and flow cytometry. Cytolytic capacity of chimeric T-cellswas studied by cytotoxicity assays in vitro and by following thegrowth curves of Gli36-EGFRvIII� xenografts stereotactically im-planted into immunodeficient mice, with or without intracranialadoptive transfer of MR1-CIR expressing T-cells in vivo.

RESULTS: By 12 weeks post transfection, clinically relevant num-bers (� 10 9), of MR1-CIR expressing T-cells were obtained, withstable expression of the MR1-CIR shown by reverse transcriptionpolymerase chain reaction and flow cytometry confirming at least 40%surface expression. Cytotoxicity assays confirmed the effective andspecific destruction of EGFRvIII� human glioblastoma cells (Gli36-EGFRvIII). The effector T-cell population was predominantly CD8�

with a CD4� subcomponent. In addition, these cells inhibited in vivotumor growth when adoptively transferred into rapidly growing in-tracranial EGFRvIII� Gli36 cells. Although all control animals died 2weeks after tumor inoculation, 60% of mice that underwent intracra-nial transfer of MR1-chimeric receptors and T-cells remained alive.

CONCLUSION: Human genetically engineered cytotoxicT-lymphocytes expressing MR1-CIR can recognize and lyse EGFRvIIIexpressing glioblastoma multiforme cells, inhibit tumor growth, andmay prolong survival. The results suggest that a Phase I study of thisapproach is needed.

896Factors Affecting Endocrine Cure after Radiosurgeryin Patients with AcromegalyJeffrey T. Jacob, B.A., Paul D. Brown, M.D.,Bruce E. Pollock, M.D.

INTRODUCTION: To review outcomes after stereotactic radiosur-gery for acromegalic patients and to analyze factors associated withbiochemical remission.

METHODS: We retrospectively analyed 46 consecutive patientswith growth hormone (GH) producing pituitary adenomas having

radiosurgery between 1991 and 2004. Endocrine cure was defined asa fasting GH less than 2 ng/ml and normal age and sex-adjustedinsulin-like growth factor I level (IGF-I) without pituitary suppressivemedications. The mean follow-up after radiosurgery was 63 months(range, 22–168).

RESULTS: Twenty-three patients (50%) had endocrine cure docu-mented at a median of 36 months (range, 6–63) after one radiosurgicalprocedure. The actuarial cure rate at 2- and 5-years after radiosurgerywas 11 and 60%, respectively. Multivariate analysis showed IGF-Ilevels less than 2.25 times the upper limit of normal (hazard ratio,2.995%; confidence interval, 1.2–6.9; P � 0.02) and the absence ofpituitary suppressive medications at the time of radiosurgery (hazardratio, 4.2, 95%; confidence interval, 1.4–13.2; P � 0.01) correlated withbiochemical remission. The incidence of new anterior pituitary deficitswas 10% at 2 years and 33% at 5 years.

CONCLUSION: Discontinuation of all pituitary suppressive med-ications at least 1 month before radiosurgery significantly improvedendocrine outcomes for acromegalic patients. Patients with GH pro-ducing pituitary adenomas should not undergo further radiation orsurgery for at least 5 years after radiosurgery because GH and IGF-Ilevels continue to normalize over that interval.

897Awake Craniotomy for Intraoperative CorticalStimulation of Language-relevant Areas: Clinical andNeurolinguistic Results of a Prospective,Longitudinal Evaluation of 153 CasesMaximilian 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 toidentify relevant sites for language processing remains the “goldstandard.” Previous studies demonstrated feasibility and usefulnessof this method. However, linguistic outcome data are rarely available.In this prospective, longitudinal study (1991–2005), we report theclinical and neurolinguistic outcome of such patients.

METHODS: Patients with lesions within and/or near suspectedlanguage-relevant areas were evaluated before surgery, within thefirst month, and within 1 year after surgery using a test battery for thedetection of aphasic disturbances (Aachener Aphasic Test). After in-traoperative stimulation and neurolinguistic testing, language rele-vant areas were marked, and the surgical approach and extent ofresection were adapted accordingly.

RESULTS: One hundred fifty-three patients were included. Awakecraniotomy 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 in94.9 and 89.2% of the patients, respectively. Prior to surgery, 16.9% ofthe patients had aphasic disturbances. Early postoperative testingrevealed 37.0% disturbances, decreasing to 15.6% within 1 year. Themajority (� 60%) of the disturbances were mild.

CONCLUSION: Direct cortical stimulation of the language-relevant areas revealed to be feasible and safe in a routine clinicalsetting. The surgical strategy could be modified according to stimu-lation results. Detailed linguistic testing demonstrated temporary andmainly mild aphasic disturbances resolving during follow-up. How-ever, not all aspects of speech and language can be adequately testedduring surgery.



898Analysis of 445 Patients with Cushing’s DiseaseTreated by Transsphenoidal SurgeryDaniel 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: Cushing’s disease (CD) is one of the most chal-lenging medical conditions to be diagnosed, confirmed, and treated.The authors review 445 patients with CD who were diagnosed andsurgically managed in a single institution from 1992 to 2005.

METHODS: There were 342 (76.8%) women and 103 men with amean age of 38.8 years (range 5–88). Twenty-seven percent of thepatients had prior surgical treatment. The mean duration of symp-toms before diagnosis was 43.7 months. Common symptoms werehypertension (68.4%), headache (39.5%), and diabetes mellitus (34%).Mean urinary free cortisol was 301 �g/24h. Mean adrenocorticotropichormone (ACTH) was 65 pg/L. Inferior petrous sinus sampling wasperformed in 53% of the patients, confirming a central source ofACTH. Magnetic resonance imaging scans detected a microadenomain 49.5% of the patients, a macroadenoma in 5%, and was equivocal in45.5%.

RESULTS: Based on preliminary analysis of 240 patients with morethan a follow-up of 2 years, tumor was visualized during 68% of theprocedures and suspected in 15%. Total hypophysectomy was per-formed in 15%, usually those who had severe CD. A fat graft wasutilized in 41%. Pathology demonstrated an ACTH staining adenomain 79%. Postoperative cerebrospinal fluid leak occurred in 2.2%. Sur-gical remission was achieved in 85.7% of patients with confirmedpathology and in 59.6% when an ACTH adenoma was not verified bythe pathologist. Among those who achieved remission, 13% recurredand usually had additional transsphenoidal surgery. In those who didnot obtain remission, gamma knife radiosurgery (31%) and adrenal-ectomy (14%) were the most common adjuvant treatments. The over-all management remission rate has been 92% with a mean follow-upof 46 months.

CONCLUSION: The treatment of CD demands a multidisciplinaryapproach. Although it can be challenging, satisfactory results can beobtained when each step in diagnosis and treatment is properly followed.

899High-frequency, Low Temperature Radiosurgery:Adjunct for Brain Tumor ResectionsAlfred P. Bowles, Jr., M.D.

INTRODUCTION: High-frequency, low temperature radio wavesurgery is gaining popularity with many surgical subspecialties in-cluding neurosurgery. With radio wave surgery, high-frequency radiowaves are directed to tissue through electrode tips. Impedance topassage of radio waves through tissue generates heat within the cells,resulting in volatilization with specific and precise cutting or coagu-lation. The radiofrequency electrode does not provide resistance andremains cold, limiting collateral damage. The paucity of heat gener-ated at the surgical site allows the surgeon to work in proximity tofunctional neuroelements.

METHODS: During an 8-month period, 90 patients ranging from 20 to73 years of age were treated for symptomatic brain tumors defined inradiographic and/or clinical progressions. Tumors consisted of cerebralmetastases, primary malignant brain tumors, and biologically malignant,

yet histologically benign brain tumors. Image-guidance was used in themajority of cases, with optimization of power intensity, wave form,frequency, and tissue contact, and with the use of a variety of electrodetips, safe, precise and thorough resections were achieved.

RESULTS: Radical resections were achieved in the majority of proce-dures and were confirmed by postoperative magnetic resonance imagingscans. Lateral thermal tissue destruction was minimized, and no newneurological defects were recorded. Variable characteristics of radiowave surgery include time of tissue contact, power intensity, and waveform, which was dependent on the variety of electrode that was used.The optimization of these characteristics achieved safe, precise, and com-plete resections in more than 80 brain tumor cases. Collateral damagewas minimized with work in direct promixity with delicate structureswith controlled hemostasis, dissection, and debulking.

CONCLUSION: Using high-frequency, low temperature radiosur-gery can be a valuable adjunct for brain tumor surgery, especiallywhen precision and total resection is mandatory.

900High Incidence of Obesity and Obesity-relatedPostoperative Complications in Male Patients withMeningiomasManish 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 menin-giomas may be explained by hormonal stimulation of meningiomagrowth. Because obesity can affect steroid hormone synthesis in males,we hypothesized that male meningioma patients might exhibit an in-creased rate of obesity, which in turn might increase the frequency ofpostoperative complications in male patients with meningioma.

METHODS: We retrospectively reviewed 32 male patients whounderwent craniotomy for resection of benign meningiomas at ourinstitution between 2001 and 2005. The controls were male patientsundergoing initial craniotomy for unruptured aneurysm (n � 32) orhigh-grade glioma (n � 32) at our hospital during the same timeperiod. Body mass index (BMI), which is based on the patient’s heightand 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; an-eurysm in 53-year-olds; glioma in 52-year-olds), male patients with me-ningioma had higher average BMI (30.2) than males experiencing aneu-rysm (BMI, 27.5) or glioma (BMI, 25.9; P � 0.04). The obesity rate in malemeningioma patients (47%) exceeded that in male patients with aneu-rysm (19%) or glioma (3%; P � 0.02). The age-normalized BMI percentilewas greater in male patients with meningioma (median, 67th percentile)than in male patients with aneurysm (49th percentile) or glioma (52ndpercentile; P � 0.02). Deep vein thrombosis/pulmonary embolus wasmore common in male patients with meningioma (19%) than in malepatients with aneurysm (0%) or glioma (3%; P � 0.002). Wound infec-tions 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 readmittedwith postoperative complications compared with 18% of nonobese pa-tients meningioma (P � 0.03). Complications included deep veinthrombosis/pulmonary embolus (27% in obese patients with meningi-oma, and 12% in nonobese patients with meningioma) and postoperativefever (53% in obese patients with meningioma, and 35% in nonobesepatients with meningioma ).



CONCLUSION: We found an increased incidence of obesity inmale patients with meningioma, suggesting a possible hormonal in-fluence on meningioma growth in males as well as females. Ourresults underscore the high risk of postoperative complications inobese male patients with meningioma.

901Intraoperative Magnetic Resonance ImagingExperience in 700 PatientsGarnette R. Sutherland, M.D., Isabelle Latour, Ph.D.,Alexander Greer, B.S.C., John K. Saunders, Ph.D.

INTRODUCTION: An intraoperative magnetic resonance imagingsystem was developed based on a ceiling-mounted 1.5T magnet. Amagnetic field strength of 1.5-T was chosen to optimize the signal-to-noise ratio. The system has been used to monitor the outcome ofneurosurgery in more than 700 patients. Intraoperative imaging pro-vides anatomical and functional data at any time during surgery.

METHODS: The system has been upgraded since 1999 to enhanceimaging and facilitate integration with neurosurgery. The system isnow marketed by Innovative Magnetic Resonance Imaging SystemsInc. (Winnipeg, Canada) and includes a 1.5-T magnet, high-performance 23mT/m gradients, and Marconi electronics. A radiofre-quency coil was developed so that the upper half could be detachedfrom the lower portion between imaging studies. The operating roomtable is based on hydraulic movement and was built from high-gradematerials compatible with magnetic resonance.

RESULTS: The patients experienced a full spectrum of neurosurgi-cal 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’ ageranged from 4 months to 84 years, with 11% of the patients youngerthan 18 years. Planning of surgical imaging updated diagnostic stud-ies, enhanced craniotomy placement and, coupled with surgical nav-igation, provided precise lesion targeting. In four patients, surgerywas aborted, as the target was either significantly reduced in size ornot evident. No lesions recurred during a 2-year follow-up. Interdis-section imaging showed unsuspected residual target in 10 to 20% ofthe patients. This was more frequently observed in patients withlow-grade glioma, epilepsy, pituitary adenoma, and C1/C2 pathol-ogy. Quality assurance imaging provided assessment of the effect ofsurgery and excluded acute complication. In one patient, acute hem-orrhage was evident and removed prior to reversal of anesthesia.

CONCLUSION: Based on the results, intraoperative magnetic res-onance imaging was found to be a valuable adjunct to neurosurgery.It allows surgeons to determine at any time during surgery the effectof surgical dissection on both the lesion and brain.

902Intraoperative Subcortical Language Tracts MappingGuides Surgical Removal of Gliomas InvolvingSpeech AreasLorenzo 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 identifyfunctional language tracts during resection of gliomas located near or

within language areas or pathways. We investigated the feasibility ofthe routine use of subcortical stimulation to identifiy language tractsin a large series of patients with gliomas, to determine the influencethat subcortical language tracts identification exerted on the extent ofsurgery, and to determine the apperance of immediate and definitivepostoperative deficits.

METHODS: Subcortical stimulation for language tracts identificationwas systematically used during surgical removal of 44 high-grade glio-mas and 44 low-grade gliomas involving language pathways. Procedureswere performed during asleep-awake craniotomy. Subcortical stimula-tion was continuously alternated with surgical resection in a back andforth fashion. Language performances were tested by neuropsychologi-cal language evaluation preoperatively and at 3, 30, and 90 days aftersurgery.

RESULTS: Language tracts were identified in 59% of the patients,with differences noted according to tumor location but not accordingto histological grade. Language tracts identification influenced theability to reach a complete tumor removal in low-grade gliomas wheretracts were documented inside the peripheral mass of the tumor.Identification of language tracts was associated with a higher occur-rence of transient postoperative deficits (69.2%), but a low (2.3%)definitive morbidity. A pattern of typical language disturbances re-lated to the phonologic and semantic system can be identified accord-ing to tumor location of which preservation is important for themaintenance of language integrity.

CONCLUSION: Our study supports the routine use of subcorticalstimulation for language tracts identification as a reliable tool for guidingsurgical removal of gliomas near or within language areas or pathways.

903Fiber Tract Navigation in Glioma SurgeryChristopher Nimsky, M.D., Oliver Ganslandt, M.D.,Daniel Weigel, M.D., Michael Buchfelder, M.D.

INTRODUCTION: To visualize the course of the pyramidal tract inthe surgical field during glioma resection by implementation of fibertract navigation supported by intraoperative imaging.

METHODS: In 57 patients with glioma (25 female; 32 male; WorldHealth 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 thesurgical field. The fiber tract seeding was based on a multiple volumeof interest approach, and functional magnetic resonance imaging dataidentified the motor gyrus as a major start region. A tensor deflectionalgorithm was used for tracking. The minimum distance betweenpyramidal tract and glioma was measured in 3-D. Hulls wrapping thefiber tract bundle visualized safety margins. Intraoperative high-fieldmagnetic resonance imaging scans were used to update the fiber tractdata, compensating for the effects of brain shift.

RESULTS: In all patients, the pyramidal tract could be visualized inthe surgical field. In six patients (10.5%), a new or aggravated post-operative paresis could be observed, which was transient in 5 of thepatients and permanent in one patient (1.7%). The pyramidal tract inthese six patients reached the segmented tumor (total, n � 31). Therisk in this subgroup for a transient deficit was 19.3% and for perma-nent defect the risk was 3.2%. No deficits were encountered in theother subgroups that contained 4, 7, and 15 patients (0–5, 5–10, and �10 mm distance). Intraoperative diffusion tensor image data wereapplied for an intraoperative update of the fiber tract information,visualizing a shifting of the pyramidal tract of up to 13 mm.



CONCLUSION: The course of the pyramidal tract can be reliablyvisualized in the surgical field by integration of fiber tract data innavigational setups. Hulls wrapping the generated 3-D object repre-senting the pyramidal tract represent safety margins. Fiber tract nav-igation combined with intraoperative imaging, updating the course ofthe pyramidal tract during surgery, compensated for the effects ofbrain shift and allowed resections with low morbidity.

904The Brainstem: A Three-dimenstional Overview ofthe Superficial Microsurgical Anatomy, SurgicalEntry Points, and 4.7-T Magnetic Resonance ImagingReconstruction of the Intraparenchymal SurgicalCorridors. A Cadaveric Database for Future RoboticSurgery and Intraoperative Magnetic ResonanceImaging ApplicationErnesto Coscarella, M.D., Mustafa Kemal Baskaya, M.D.,Jacques J. Morcos, M.D.

INTRODUCTION: We reviewed the anatomy of the fiber tracts andcranial nerve nuclei of the brainstem from a microsurgical point ofview and established an anatomical correlate for safe entry zones viathe most direct surgical approach.

METHODS: Surgical and surface anatomy of the brainstem werestudied in injected cadaveric heads. The brainstem was disconnectedfrom the cerebellum, thalamus, and spinal cord in order to study thesurface anatomy and safe entry zones. Each brainstem was scannedfor 24 consecutive hours with a 4.7-T research magnetic resonanceimaging (MRI) scanner to identify fibers and nuclei. The relationshipto each possible surgical path was examined through the creation ofsimulated surgical trajectories.

RESULTS: Anatomical and radiological details were obtained. Thestudy demonstrated how the data could be used in planning safersurgical pathways into the brainstem through more logical entryzones. This database could be a platform to be included into anintraoperative MRI system as well as an anatomical interactive mapfor guiding robotic surgery through eloquent areas of the brain.

CONCLUSION: In this preliminary study, we showed the feasibilityof high-strength MRI cadaveric imaging of brainstem anatomy. We ex-tended the concept of the surgical application into the study of safer entryzones. The presentation was enhanced by three-dimentional exposition.We predicted a wide application of the technique in the field of surgicaleducation, virtual simulation, and anatomical expositions.

905Patients’ Outcome at Long-term Follow-up afterAggressive Microsurgical Resection of PetroclivalMeningiomasSabareesh 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 sur-vival at long-term follow-up after aggressive microsurgical resectionof petroclival meningiomas.

METHODS: Over a 13-year period (1991–2003), 150 patients under-went 220 operative procedures for resection of petroclival meningiomas.The tumor size was large to giant in most cases, with a mean tumordiameter of 3.3 � 1.1 cm. Tumors extended into adjoining regions.

Thirty-three patients (22%) were previously treated, and 117 patients(78%) were previously untreated. Eighty-nine patients (59%) had a singleoperation, and 61 patients (41%) had more than one operation. Postop-erative radiation was given to 33 patients who had residual tumors.Gross tumor resection was accomplished in 59 patients (39%), subtotalresection in 75 patients (50%), and partial resection in 16 (11%) patients.There were no operative deaths. Postoperative complications (cerebro-spinal fluid leakage, quadriparesis, infections, cranial nerve palsies, etc.)were observed in 21 patients (14%). Patients were evaluated by question-naires and review of their recent radiological images.

RESULTS: The mean follow-up is 71 months with a range of 3 to179 months. At the conclusion of the study, 141 patients were alivewithout disease progression or recurrence. Nine patients (7%) hadrecurrence (five patients after incomplete resection, four after totalresection) of which one died, one underwent repeat resection, andseven were treated by radiotherapy. The Karnofsky Performance Scalescore was 78 � 11 preoperatively, 77 � 16 at 1 year postoperatively,and 77 � 15 at the latest follow-up. Common disabilities at follow-upincluded 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 com-plete surgical resection or a combination of surgery and radiotherapy.About 93% of the patients survived without recurrence at long-termfollow-up. The functional status of the surviving patients was excel-lent at follow-up in most patients. This article presents the longestfollow-up of petroclival meningiomas in the microsurgical era.

906Surgical Management of Primary and MetastaticSarcomas of the Mobile SpineGanesh 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 theirextensive involvement of multiple spinal segments and high recurrencerates. Gross total resection with preservation of neurological function andpalliation is the goal and may be achieved with either intralesionalresection or en bloc resection. We report outcomes of surgery for primaryand metastatic sarcomas of the mobile spine in a large series.

METHODS: A retrospective review of patients undergoing surgicalresection for sarcomas of the spine from 1993 to 2005 was undertaken.Sarcomas were classified by histology and as either primary or met-astatic. Details of the surgical approach, levels of involvement, andoperative complications were recorded. Survival was the main out-come measure. Secondary outcome measures included recurrent dis-ease, neurologic function, and palliation.

RESULTS: Eighty patients underwent 113 surgical resections ofeither primary or metastatic sarcomas of the mobile spine. Twenty-eight patients (35%) experienced primary sarcomas, and 52 patients(65%) experienced metastatic sarcomas. The most common histologywas chondrosarcoma (26%). Intralesional resections were performedin 101 surgeries (89%), and en bloc resections were performed in 12(11%). Median survival was 21.5 months. There was no significantdifference in survival between intralesional or en bloc resection (P �0.51). Local recurrence rates were 36 and 16% for intralesional versusen bloc resections, respectively. Complications occured in 13 patients(11.5%). Metastatic disease predicted increased survival in univariateanalysis. There was a trend toward significant improvement in Amer-ican Spinal Injury Association motor scores postoperatively (P � 0.08)



and a significant decrease in pain scores postoperatively (P � 0.003)for patients undergoing surgical resection.

CONCLUSION: Surgery for primary or metastatic sarcoma of thespine is associated with an improvement in neurologic function and apalliative effect. Treatment for metastatic rather than primary diseasewas predictive of prolonged survival. Local recurrence rates werelower for en bloc resections; however, there was no significant differ-ence in survival for intralesional versus en bloc resections.

907Gamma Knife Radiosurgery for MalignantMelanoma Brain MetastasesDavid 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 leadingcauses of brain metastases and is associated with a high rate ofneurological morbidity and mortality. Patient survivals rates arelower compared with other metastases due to the limited options formanagement of active extracranial disease. We reviewed a series ofpatients who underwent radiosurgery for melanoma brain metastasesand assessed clinical outcome to identify prognostic factors for sur-vival and cerebral disease control.

METHODS: Two hundred and forty-four patients underwent radio-surgery for the management of 754 metastatic tumors during an 18-yearperiod. A mean of 2.6 tumors were irradiated per procedure. The mediantotal tumor volume was 4.4 cm3. The median margin and maximumdoses used were 18 and 32 Gy, respectively. Kaplan-Meier and Coxregression analyses were performed to assess outcome and prognosis.

RESULTS: After radiosurgery, the median survival for the entireseries was 5.3 months. Improved survival was seen with controlledextracranial disease (12.7 mo), Karnofsky Performance Scale score of90 or 100% (6.3 mo), single brain metastasis (6.8 mo), total tumorvolume 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 associatedwith local failure after radiosurgery. Multiple lesions at radiosurgeryand absence of subsequent immunotherapy were predictors for theoccurrence of new brain metastases, which developed in 41.7% ofpatients. Symptomatic radiation changes were seen in 6.6% of pa-tients. Overall, 71.4% of patients improved or remained stable afterradiosurgery, and 52.4% of patients were able to discontinue or re-main off corticosteroids.

CONCLUSION: Gamma knife radiosurgery for malignant mela-noma brain metastases is safe and effective with a high rate of durabletumor control.

908Akt/PKB Activation Facilitates Immune Escape inGlioma PatientsJames 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 hasbeen recently refined to include three steps: elimination, equilibrium,and escape. In the first phase of elimination, cells and molecules of the

innate and adaptive immune system can eradicate developing tumors.If this process is not successful, then tumor cells enter the equilibriumphase where they may be maintained chronically or immunologicallysculpted to produce tumor variants. In this study, we showed that Aktactivation was a key step in immune escape for glioma.

METHODS: Functional impact of Akt activation was measuredusing an alloreactive T-cell apoptosis assay. After determining thatAkt activation facilitated experimental glioma cell lines and culturesto cause apoptosis of T-cells, we evaluated patient samples in anautologous fashion. Fifteen patients were screened for Akt pathwayactivation in low passage primary glioma cultures. Autologous pe-ripheral blood lymphocytes were cocultured with matching gliomacultures, and apoptosis of T-cells was measured using flow cytometryand Annexin staining with 7-AAD.

RESULTS: Six patients had significant activation of the Akt path-way as measured by Western blotting of the phosphorylated Akt anddownstream target S6K1. Coculture of autologous peripheral bloodlymphocytes with these six samples resulted in induction of T-celldeath (range, 46–52%; average apoptosis per sample in triplicate after2 hour 1:1 coculture; nonspecific stimulation of T-cells, P � 0.01 ascompared to 9 patients with low Akt activity). Treatment of gliomacultures with wortmannin (a PI3Kinase inhibitor), CCI-779 (mTORinhibitor), and a direct Akt inhibitor abrogated this effect (12–16%average apoptosis, P � 0.01). The nine patients with low Akt activityhad minimal effect upon T-cells (6–12% average apoptosis).

CONCLUSION: We provided direct evidence from glioma patientsthat Akt pathway activation in glioma was associated with inductionof apoptosis of cocultured T-cells. Our results may explain the failureof T-cell mediated immunotherapy in some glioma patients and pro-vides the impetus for immunotherapy in combination with Akt path-way inhibitors.

909Changing Trends in the Utilization and Costs ofProcedures Performed by Neurosurgeons in theUnited States.John A. Cowan, Jr., M.D., William F. Chandler, M.D.

INTRODUCTION: Understanding the changes in procedure utili-zation and total cost associated with the care of patients is importantto the practice of neurosurgery. This investigation quantified theoverall trends in discharge rates and hospital charges for procedurescommonly performed by neurosurgeons in the United States.

METHODS: Clinical data was collected from the Nationwide Inpa-tient Sample for the years 1997 to 2003. Diagnostic related groups thatpertain to procedures performed by neurosurgeons (groups 1–8, 214,215, 484, 496–500, 519, 520, 529–532) were used to generate theweighted sample population (estimated n � 6,172,258). Dischargesand total hospital charges annually for craniotomy, spinal procedures(with and without fusion), peripheral nerve procedures, and extracra-nial vascular procedures were assessed. Population adjustments weremade based on United States Census Bureau data and dollar valueswere adjusted using the consumer price index for hospital-relatedservices.

RESULTS: Overall hospital discharges increased from 823,972 in1997 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 spinalfusion. Discharges for craniotomy increased from 142,622 to 163,669(14%) annually (P � 0.06). The total charges increased from $10.5 to



$20.8 billion for all spinal procedures (P � 0.001) and from $7.0 to$10.3 billion for craniotomies (P � .001). Peripheral nerve proceduresincreased by $1 billion (P � 0.001), and extracranial vascular proce-dures decreased by $0.5 billion (P � 0.003).

CONCLUSION: Spinal procedures experienced large increases inoverall utilization and charges during the studied period. There was a

dramatic increase in the number of spinal fusions. Smaller increaseswere found for craniotomy and peripheral nerve procedures. Ex-tracranial vascular procedures experienced a decline in both utiliza-tion and charges. The findings demonstrates the dynamic nature ofthe contemporary practice of neurosurgery and have implications forfuture workforce, training, and research needs.

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


awake craniotomy for intraoperative cortical.144

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