volume 8 number 3 ucsf department of neurological surgery news academic and research news

New Interventional MRI System Developed to Improve Surgery for Movement Disorders

Deep brain stimulation (DBS) has using this technique at UCSF. The fewer brain penetrations may lead been used for over a decade to subthalamic nucleus (STN) is by to less confusion postoperatively, treat movement disorders such far the most common brain target particularly in older patients. It as Parkinson’s disease, essential for DBS in Parkinson’s disease may ultimately result in a lower tremor, and dystonia. It has become and is visible on 1.5T MR images. hemorrhage risk as well, but this the gold standard for surgical care of In traditional DBS surgery, MER is remains to be established. these diseases; over 40,000 patients used to map the STN and locate In 2008, Larson, Starr, and Martin have had DBS devices implanted the center of its motor region, the partnered with the medical device worldwide. DBS uses a pulse area which has been shown to be company SurgiVision to develop generator implanted in the chest, effective in reducing symptoms new technologies for the iMRI DBS similar to a pacemaker, to deliver when stimulated. With iMRI, the technique. This includes an MRI- pulses to specific regions of the surgeons can see this region directly compatible, skull-mounted aiming brain via a permanently implanted and can place the DBS electrode device and MR coils specifically electrode. The traditional method without the need for MER. designed to provide optimal imaging of surgical implantation involves In conjunction with Alastair Martin during surgery. They have also placement of a stereotactic head PhD in the Department of Radiology, developed a software environment frame and an awake implantation Jill Ostrem MD in the Department that will standardize the implantation procedure using a technique known of , and others, Starr and procedure on different MRI platforms. as microelectrode recording (MER). Larson developed a technique of The new software environment will During MER, the surgeon passes implantation using a modified but stream data from any manufacturer’s small microelectrodes into the region commercially available skull-mounted 1.5T MRI scanner and guide the of the intended target and observes aiming device and custom-made, surgeon through the implantation the pattern of neuronal activity to MR-compatible surgical instruments. procedure using a specially designed physiologically confirm accurate After validating the techniques with graphical interface. The software will placement of the stimulating numerous phantom studies, they also improve accuracy by automating electrode. Although this technique began performing iMRI implantations some steps that were previously is widely used, it is technically in patients in 2004. To date they dependent on the user. The UCSF demanding, time consuming, and have implanted 67 electrodes in 36 group and SurgiVision will be testing often difficult for patients to tolerate. patients using this technique. iMRI and validating the new system this Interventional MRI (or iMRI) allows DBS has several distinct advantages spring and summer. surgeons to take advantage of MR over traditional implantation imaging in real time by performing methods. There is no need for a procedures inside the scanner stereotactic frame and no need for Martin AJ, Larson PS, Ostrem JL, Sootsman WK, itself. Paul Larson MD, assistant the patients to be awake and off of Talke P, Weber OM, Levesque N, Meyers J, Starr PA. Placement of deep brain stimulator electrodes using professor of neurological surgery, their Parkinson’s medications, so real-time high-field interventional magnetic resonance and Philip Starr MD, PhD, Dolores patients tolerate the procedure well. imaging. Magn Reson Med 2005;54(5):1107-1114. Cakebread Endowed Chair and The procedure time is half that of Martin AJ, Larson PS, Ostrem JL, Starr PA. associate professor of neurological traditional MER-guided implantation, Interventional magnetic resonance guidance of deep brain stimulator implantation for Parkinson disease. surgery, were both involved with this and since MER is not necessary Top Magn Reson Imaging 2008;19(4):213-221. technology during its development there is only one brain penetration in the 1990s. In 2002, they began needed in the vast majority of cases. to think about how to perform DBS The shorter operative times and University of a The interventional MRI suite at UCSF Medical Center. b The ClearPoint software allows the surgeon to view the MR images in different orientations to guide DBS electrode implantation. Neurological Surgery c The SmartFrame mounts on the patient’s skull and helps guide the DBS electrode into the brain. a b c Department of Neurological Surgery , San Francisco 400 Parnassus Avenue, 8th Floor Box 0350 San Francisco, CA 94143-0350 Phone: 415/353-7500 Fax: 415/353-2889 http://neurosurgery.ucsf.edu looking to the future

Treatment for movement disorders disorders, define new surgical – like Parkinson’s disease, dystonia, targets, and develop novel or tremor – was once exclusively treatments. A major source of medical, but technologies have excitement arising from basic evolved that permit remarkable science studies has been the improvement for patients who are advancement of gene therapy. A treated surgically. In 2001, one of recently completed phase I study for six national Parkinson’s Disease Parkinson’s disease, led by Michael Research, Education and Clinical Aminoff MD in the UCSF Department Centers (PADRECC) was established of Neurology, demonstrated the at the San Francisco Veterans Affairs safety of convection-enhanced Medical Center, and it has since delivery (CED) of the gene for the Stem cell research is yet another become one of the largest referral enzyme aromatic L-amino acid promising avenue for scientific centers for movement disorder decarboxylase (AADC). This enzyme investigation, and recent changes in surgery in the United States. The converts L-dopa (the standard laws regarding funding has opened surgical movement disorders medical therapy for Parkinson’s the floodgates for numerous studies program is led by Philip Starr MD, disease) into dopamine. CED involving the use of stem cells to PhD and Paul Larson MD who infusion of viral vectors carrying the treat neurological disorders. The have expertise in stereotactic and gene for AADC was pioneered in Buck Institute (led by Xianmin Zeng functional neurosurgery, including the laboratory of Krystof Bankiewicz PhD) and a team at UCSF (led by deep brain stimulation (DBS), which MD, PhD over decades of research Lim, Aminoff, and William Marks has dramatically transformed the using animal models of Parkinson’s MD of the Department of Neurology) quality of life of many patients disease, and if the therapy is have recently applied for funding suffering with Parkinson’s disease. successful, patients may require to design a phase I transplantation In 2008, they were joined by clinician- less medication to achieve the therapy trial testing dopaminergic scientist Daniel Lim MD, PhD, a same level of symptom control, neurons derived from human former resident in the Department reducing dose-related side effects. embryonic stem cells. If the grant who trained under Larson and Starr in Although it was not a randomized, is funded, UCSF may someday be stereotactic neurosurgical techniques. controlled trial, all 10 patients one of first sites at which human 2 enrolled in the phase I study showed embryonic stem cells are used for While the advent of new technology significant improvement in off-label the treatment of Parkinson’s Disease. has helped lessen the severity of Unified Parkinson’s Disease Rating patients’ symptoms, we continue Scale scores. These results are to invest in research to improve encouraging and warrant further treatments and attack the underlying investigations in placebo-controlled disease. One way we are improving clinical trials. existing treatments is by making them less invasive. Starr and Larson While gene therapy has suffered have recently partnered with the from a variety of setbacks in past Mitchel S. Berger MD, medical device company SurgiVision trials, including those for movement Kathleen M. Plant to develop the first system using disorders, we are optimistic that Distinguished Professor & Chairman interventional MR imaging for DBS with continued investigation, the Director, Brain Tumor (page 1). The new technology hurdles of this promising treatment Research Center obviates the need for a stereotactic strategy will be overcome. Starr and frame, reduces the number of brain Bankiewicz are also collaborating Department of penetrations to one, and shortens with Nutan Sharma (Massachusetts Neurological Surgery, UCSF operating times. General ) to explore an animal model of DYT1+ dystonia In the laboratory, we are leading created by convection-enhanced studies to understand the delivery to the brain of viral vectors pathophysiology of movement expressing the mutant Tor1A gene. Typical DBS lead location in the putamin in a patient with dystonia

Dystonia: Surgical Treatment and Advances in Pathophysiology

Dystonia is the third most common Foundation (BEBRF), Ostrem and 1. Starr PA, Turner RS, Rau G, et al. movement disorder, after Parkinson’s Philip Starr MD, PhD, associate Microelectrode-guided implantation of deep brain stimulators into the globus pallidus disease and essential tremor. professor of neurological surgery, internus for dystonia: techniques, electrode Its hallmark is excessive muscle are conducting a pilot trial of an locations, and outcomes. activity, in particular, simultaneous alternative target in dystonia, the J Neurosurg 2006;104(4):488-501. contraction of muscle groups that subthalamic nucleus (STN).4 2. Berman BD, Starr PA, Marks WJ Jr, Ostrem JL. Induction of bradykinesia with pallidal deep normally oppose each other. It has Understanding the pathophysiology brain stimulation in patients with cranial- numerous clinical manifestations, cervical dystonia. Stereotact Funct Neurosurg of dystonia has been a primary ranging from severe, life-threatening 2009;87(1):37-44. interest of Starr’s basal ganglia juvenile onset generalized forms 3. Ostrem JL, Marks WJ Jr, Volz MM, Heath SL, physiology laboratory. Using single Starr PA. Pallidal deep brain stimulation in to adult onset focal dystonias unit recording techniques in humans patients with cranial-cervical dystonia (Meige such as spasmodic torticollis and syndrome). Mov Disord 2007;22(13):1885-1891. undergoing awake neurosurgery, his blepharospasm. Its pathophysiology 4. Ostrem JL, Volz MM, Starr PA. Deep brain group has defined the abnormalities is poorly understood. stimulation (DBS) of the subthalamic nucleus in single unit neuronal firing in three (STN) in patients with segmental and focal The UCSF center for the surgical basal ganglia nuclei, the GPi,5, 6 the cervical dystonia [abstract]. Mov Disord 3 2008;23(suppl 1):S380. treatment of movement disorders STN, and the external pallidum.7 In 5. Starr PA, Rau GM, Davis V, Marks WJ Jr, is one of the two busiest centers in 2008, these physiology studies were Ostrem JL, Simmons D, Lindsey N, Turner the United States for the surgical extended to include cortical function, RS. Spontaneous pallidal neuronal activity in treatment of dystonia. Working with assessed using electrocorticography human dystonia: comparison with Parkinson’s disease and normal macaque. J Neurophysiol Jill Ostrem MD from the Department techniques. Working with a Doris 2005;93(6):3165-3176. of Neurology, UCSF neurosurgeons Duke fellow in the Starr laboratory, 6. Chang EF, Turner RS, Ostrem JL, Davis have performed deep brain stimu- Andrea Crowell, the group has VR, Starr PA. Neuronal responses to passive lation (DBS) for various forms of discovered characteristic oscillation movement in the globus pallidus internus in primary dystonia. J Neurophysiol dystonia in over 80 patients. Our frequencies in both the cortex and 2007;98(6):3696-3707. center is the first to describe the basal ganglia that appear to encode 7. Sani S, Ostrem JL, Shimamoto S, Levesque technique of microelectrode-guided the dystonic phenotype.8 The Starr N, Starr PA. Single unit “pauser” characteristics DBS in awake patients.1 laboratory has also recently received of the globus pallidus pars externa distinguish primary dystonia from secondary dystonia and a grant from the Dystonia Medical The accepted brain target for DBS Parkinson’s disease. Exp Neurol 2009; Research Foundation to investigate 216(2):295-259. in dystonia has been the major STN and motor cortex local field outflow nucleus of the basal ganglia, 8. Crowell A, Ostrem JL, Shimamoto S, Starr PA. potentials in patients with dystonia. Cortical and subthalamic local field potentials in the globus pallidus internus (GPi). primary dystonia. Presented at: 15th quadrennial These studies are helping to decode However, our group has shown that, meeting of the World Society of Stereotactic and the pathophysiology of dystonia, Functional Neurosurgery; May 24-27, 2009; in adult onset focal dystonias, GPi- provide a window on function of Toronto, Canada. DBS may be associated with subtle the basal ganglia, and may lead to deficits (slowness) in previously new targets for the treatment of this normal body parts.2, 3 Funded mysterious disorder. with a seed grant from the Benign Essential Blepharospasm Research selected publications During his residency, Dr. Glass GA, Ku S, Ostrem JL, Heath S, Larson Larson was extensively involved PS. Fluoroscopic, EMG-guided injection in the development of the Norton of botulinum toxin into the longus colli for Hospital intraoperative MRI the treatment of anterocollis [published online ahead of print February 26, 2009]. program, and spent a year in the Parkinsonism Relat Disord doi:10.1016/j. Speed School of Engineering’s parkreldis.2009.01.006 Computer Vision and Image Martin AJ, Larson PS, Ostrem JL, Starr PA. Processing Lab studying the Interventional magnetic resonance guidance of deep brain stimulator implantation for basic science of CT and MR Parkinson disease. Top Magn Reson Imaging image analysis and 3D modeling. 2009;19(4):213-221. Paul Larson MD, assistant professor Richardson RM, Larson PS, Bankiewicz KS. of neurological surgery, has clinical Dr. Larson’s research interests Gene and cell delivery to the degenerated interests in stereotactic and include neurostimulation, striatum: status of preclinical efforts in primate functional neurosurgery, particularly gene therapy, and other models. Neurosurgery 2008;63(4):629-644. with regard to movement disorders neurorestorative therapies for a Marks WJ Jr, Ostrem JL, Verhagen L, Starr PA, Larson PS, Bakay RA, Taylor R, Cahn-Weiner and psychiatric disorders. He has variety of neurological diseases, DA, Stoessl AJ, Olanow CW, Bartus RT. Safety been involved in the development including movement disorders and and tolerability of intraputaminal delivery of and evolution of novel surgical psychiatric disorders. He is also CERE-120 (adeno-associated virus serotype 2-neurturin) to patients with idiopathic methods for deep brain stimulator involved in studies using high- Parkinson’s disease: an open-label, phase I implantation, including frameless field MR brain imaging for clinical trial. Lancet Neurol 2008;7(5):400-408. techniques and the use of high-field, and basic science research. His real-time intraoperative magnetic basic science interests include resonance imaging (MRI). He has MR research and the development extensive surgical experience in of new technologies to perform the use of intraoperative MRI for a functional neurosurgery using number of neurosurgical applications. real-time MRI. focus on faculty

4 Nader Sanai MD was born in journal Neurosurgery Clinics of North Tehran, Iran and raised in Palo Alto, America, and is currently an Associate California. He attended UCSD as an Editor for the journal BMC Cancer. undergraduate, where he double- Sanai began his neurosurgical majored in Animal Physiology & training at UCSF in 2004, and under Neuroscience and French Literature. the mentorship of his advisor, Mitchel His initial interest in neurosurgery Berger MD, he has conducted a stemmed from his family’s number of studies focusing on surgi- experience caring for his mother’s cal neuro-oncology, intraoperative sister, who died from a glioma. language mapping, and the biology In 1998, Sanai entered the UCSF of gliomagenesis. Within surgical School of Medicine, where he first neuro-oncology, his area of clinical joined the laboratory of Dennis Deen specialization has also extended selected publications PhD in the Brain Tumor Research into lesions of the skull base. Among Center and was selected as the first various clinical honors, Sanai Sanai N, Berger MS. Glioma extent of resection and its impact on patient outcome. recipient of the Diane D. Ralston & received the Kaiser Award for Clinical Neurosurgery 2008;62(4):753-764. Henry J. Ralston Scholarship for Research from the San Francisco Sanai N, Mirzadeh Z, Berger MS. Functional Research in Neurosciences. In 2001, Neurological Society and the outcome after language mapping for glioma he was awarded a Howard Hughes Dandy Clinical Fellowship from the resection. N Engl J Med 2008;358(1):18-27. Medical Institute (HHMI) Research Congress of Neurological Surgeons. Sanai N, Alvarez-Buylla A, Berger MS. Training Fellowship to conduct Neural stem cells and the origin of gliomas. After finishing his neurosurgical research in the laboratory of Arturo N Engl J Med 2005;353(8):811-822. training at UCSF in 2009, Sanai will Alvarez-Buylla PhD, studying adult Sanai N, Tramontin AD, Quiñones-Hinojosa complete a fellowship in skull base A, Barbaro NM, Gupta N, Kunwar S, Lawton neural stem cells in the human brain. surgery with Robert F. Spetzler MD MT, McDermott MW, Parsa AT, Manuel-García Among various basic science honors, Verdugo J, Berger MS, Alvarez-Buylla A. at the Barrow Neurological Institute Sanai received the Edwin F. Boldrey Unique astrocyte ribbon in adult human brain in Phoenix, AZ. He then anticipates a contains neural stem cells but lacks chain Award for Basic Science Research migration. Nature 2004;427(6976):740-744. career in academic neurosurgery as from the San Francisco Neurological both a surgical neuro-oncologist and Society, served as Guest Editor for neural stem cell scientist. the Neural Stem Cells issue of the resident gazette resident Philip Starr MD, PhD, is the lation (DBS) currently taking place Dolores Cakebread Endowed in North America: “A Randomized Chair and associate professor of Trial of Best Medical Therapy versus neurological surgery. His particular Deep Brain Stimulation of the Globus specialty interests lie in the area Pallidus or Subthalamic Nucleus of movement disorders, including for Parkinson’s Disease.” This is a Parkinson’s disease, tremor, and six-center trial jointly funded by the dystonia. He has fellowship training Department of Veterans Affairs and in microelectrode-guided surgery the National Institutes of Health. of movement disorders, which he Starr also conducts NIH-funded selected publications completed at Emory University in research on pallidal physiology in Chang EF, Turner RS, Ostrem JL, Davis Atlanta, Georgia. Starr’s research patients with dystonia. VR, Starr PA. Neuronal responses to interests include physiology of the passive movement in the globus pallidus The goal of Starr’s research laboratory internus in primary dystonia. J Neurophysiol basal ganglia, clinical trials of novel is to understand the pathophysiology 2007;98(6):3696-3707. surgical therapeutics in movement of movement disorders by recording Starr PA, Kang GA, Heath S, Shimamoto S, disorders, and the use of interven- electrical activity in humans undergo- Turner RS. Pallidal neuronal discharge in tional magnetic resonance imaging Huntington’s disease: support for selective ing microelectrode-guided basal loss of striatal cells originating the indirect (iMRI) for functional neurosurgery. ganglia surgery in the awake state. pathway. Exp Neurol 2008;211(1):227-233. Working together with William Data gathered are used to confirm, Sillay KA, Larson PS, Starr PA. Deep brain Marks MD and Jill Ostrem MD in the refute, or expand upon existing stimulator hardware-related infections: incidence and management in a large series. Department of Neurology in a joint models of basal ganglia function and Neurosurgery 2008;62(2):360-366. UCSF-San Francisco Veterans Affairs dysfunction, to identify possible new Sani S, Ostrem JL, Shimamoto S, Levesque N, Hospital Medical Center study, Starr surgical targets, and to provide a bet- Starr PA. Single unit “pauser” characteristics is an investigator for the largest for- ter understanding of the mechanism of the globus pallidus pars externa distinguish primary dystonia from secondary dystonia mal clinical trial of deep brain stimu- of action of brain stimulation. and Parkinson’s disease. Exp Neurol 2009; 216(2):295-259.

5 James Waldron MD received his after becoming a resident in the undergraduate degree from Rice Department of Neurological Surgery, University in Houston, TX and winning the Preuss Award for Brain attended medical school at the Tumor Research at the Congress of University of Texas, Southwestern Neurological Surgeons in 2006 and School of Medicine in Dallas, TX, receiving an NIH National Research where he graduated first in his Service Award to support a year class. While at UT Southwestern of dedicated research in glioma he completed a summer research immunology. Waldron was selected fellowship in the laboratory of to receive the Integra Foundation Nobel laureates Michael Brown Award at the 2009 Annual Meeting MD and Joseph Goldstein MD, of the American Association of studying cholesterol metabolism. Neurological Surgeons for his work After graduation he completed an looking at preoperative embolization internship in Internal Medicine at of skull base tumors. Waldron’s selected publications Brigham and Women’s Hospital, academic and clinical interests have Waldron JS, Lawton MT. The supracarotid- Harvard Medical School, followed broadened to include the treatment infrafrontal approach: surgical technique and clinical application to cavernous malformations by a period of time in the business of cerebrovascular disease. He in the anteroinferior Basal Ganglia. Neurosurgery sector working as a consultant in has worked closely with Michael 2009;64(3 Suppl):86-95. the healthcare practice of McKinsey Lawton MD developing skills in Waldron JS, Halbach VV, Lawton MT. & Company. open cerebrovascular surgery Microsurgical management of incompletely coiled and recurrent aneurysms: trends, and publishing on the surgical techniques, and observations on coil extrusion. In 2002, Waldron joined the treatment of previously coiled Neurosurgery (In Press). laboratory of Andrew Parsa MD, aneurysms and the removal of Parney IF, Waldron JS, Parsa AT. Flow cytometry PhD in the Brain Tumor Research and in vitro analysis of human glioma-associated cavernous malformations from the Center at UCSF as a postdoctoral macrophages. Laboratory investigation. basal ganglia. After graduation, J Neurosurg 2009;110(3):572-582. research associate studying glioma Waldron will pursue an endovascular Parsa AT, Waldron JS, Panner A, Crane CA, immunology and the underlying fellowship at Stanford University, and Parney IF, Barry JJ, Cachola KE, Murray JC, mechanisms that allow gliomas to Tihan T, Jensen MC, Mischel PS, Stokoe focus his academic efforts on the escape the immune system. Waldron D, Pieper RO. Loss of tumor suppressor development of endovascular drug- PTEN function increases B7-H1 expression continued to work closely with Parsa and immunoresistance in glioma. Nat Med delivery techniques. 2007;13(1):84-88. neurosurgery notes

Manish Aghi MD, PhD, assistant Nicholas Barbaro MD, professor of Department of Neurological Surgery, professor of neurological surgery, has neurological surgery, has received have developed a new surgical tech- been awarded a James S. McDonnell a $21 million grant from the NIH nique for placing expandable cages Foundation Grant for $450,000 over 4 to fund the Radiosurgery or Open from the back. The approach avoids years for the project “Identifying and Surgery for Epilepsy (ROSE) Trial – dissecting the pleura, potentially overcoming glioblastoma resistance a phase III randomized clinical trial preventing pulmonary issues when to treatments targeting vascular of Gamma Knife® radiosurgery for putting in these cages. endothelial growth factor.” He has mesial temporal sclerosis. Chou D, Wang VY. Trap-door also been granted a Specialized Mitchel S. Berger MD, Kathleen rib-head osteotomies for posterior Programs of Research Excellence M. Plant Distinguished Professor placement of expandable cages Career Development Award from and chairman of the Department after transpedicular corpectomy: an the National Institutes of Health of Neurological Surgery, has been alternative to lateral extracavitary and (NIH) for the project “Identifying honored with the prestigious Winn costotransversectomy approaches. and overcoming mechanisms of Prize from the Society of Neurological J Neurosurg Spine 2009;10(1):40-45. resistance to antivascular agents in Surgeons. The Winn Prize acknowl- human glioblastoma.” Joseph Costello PhD, associate edges outstanding clinical and/or professor of neurological surgery, Krystof Bankiewicz MD, PhD, translational research conducted has been awarded a grant for Kinetics Foundation Chair in by an academic neurosurgeon. $12 million over the next 5 years Translational Research and profes- Edward Chang MD, resident in as part of the new NIH Roadmap sor of neurological surgery, and the Department of Neurological Epigenomics Program. Costello his colleagues have successfully Surgery, received the Ronald L. will lead the Integrated Epigenetic administered adeno-associated virus Bittner Award at the 2009 Annual Maps of Human Embryonic and (AAV)-based gene therapy vectors to Meeting of the American Association Adult Cells project in conjuction specific areas of the primate cortex of Neurological Surgeons (AANS) with Marco Antonio Marra PhD at by infusing the vectors into the for the research article “Multi- the British Columbia Cancer Agency. thalamus via convection enhanced institutional validation of the delivery. The gene therapy vectors Nikita DeGurin, specialist in the University of California at San efficiently disperse through axons that Department of Neurological Surgery, Francisco Low-Grade Glioma connect the thalamus and the cortex. recently implanted the first tissue- 6 Prognostic Scoring System.” engineered vascular graft made Kells AP, Hadaczek P, Yin D, Jacqueline Bresnahan PhD, adjunct with nanofibrous polymer scaffolds Bringas J, Varenika V, Forsayeth professor of neurological surgery, has and lined with human embryonic J, Bankiewicz KS. Efficient gene been appointed chair of the Scientific stem cell-derived progenitor cells, therapy-based method for the Advisory Board for the Christopher replacing a carotid artery in a swine delivery of therapeutics to primate and Dana Reeve Foundation. (see photo). This was a joint project cortex. Proc Natl Acad Sci USA with Randell Lee MD, PhD of the 2009;106(7):2407-2411 Dean Chou MD, assistant professor Department of Medicine and Song Li of neurological surgery, and Vincent PhD of the UC Berkeley Department Wang MD, PhD, resident in the of Bioengineering.

residents’ publications

Chang EF, Clark A, Jensen RL, Bernstein M, Guha Potts MB, Rola R, Claus CP, Ferriero DM, Fike JR, Tate CC, Shear DA, Tate MC, Archer DR, Stein DG, A, Carrabba G, Mukhopadhyay D, Kim W, Liau Noble-Haeusslein LJ. : Glutathione peroxidase Laplaca MC. Laminin and fibronectin scaffolds LM, Chang SM, Smith JS, Berger MS, McDermott overexpression does not rescue impaired enhance neural stem cell transplantation into MW. Multiinstitutional validation of the University neurogenesis in the injured immature brain. the injured brain. J Tissue Eng Regen Med of California at San Francisco Low-Grade Glioma J Neurosci Res 2009;87(8):1848 – 1857. 2009;3(3):208-217. Prognostic Scoring System [published online Quiñones-Hinojosa A, Chang EF, Chaichana KL, Wang VY, Deviren V, Ames CP. Reconstruction of ahead of print March 6, 2009]. J Neurosurg. McDermott MW. Surgical considerations in the C-1 lateral mass with titanium mesh cage after doi: 10.3171/2009.2.JNS081101. management of falcotentorial meningiomas: resection of an aneurysmal bone cyst of the atlas. Lim DA, Tarapore P, Chang E, Burt M, Chakalian L, advantages of the bilateral occipital transtentorial/ J Neurosurg Spine 2009;10(2):117-121. Barbaro N, Chang S, Lamborn KR, McDermott MW. transfalcine craniotomy for large tumors. Yang I, Aranda D, Han SJ, Chennupati S, Sughrue Safety and feasibility of switching from phenytoin to Neurosurgery 2009 64(ONS Suppl 1): ME, Cheung SW, Pitts LH, Parsa AT. Hearing levetiracetam monotherapy for glioma-related seizure ons260–ons268. preservation after stereotactic radiosurgery for control following craniotomy: a randomized phase II Sanai N, Tarapore P, Lee AC, Lawton MT. The vestibular schwannoma: A systematic review pilot study [published online ahead of print January current role of microsurgery for posterior circulation [published online ahead of print March 20, 2009]. J 24, 2009]. J Neurooncol. doi: 10.1007/s11060-008- aneurysms: a selective approach in the endovascular Clin Neurosci. doi:10.1016/j.jocn.2008.09.023 9781-4. era. Neurosurgery 2008;62(6):1236-1253. Yang I, Delpolyi A, Sughrue ME, Rubenstein J, Lu DC, Dhall SS, Mummaneni PV. Mini-open removal Sughrue ME, McDermott MW, Parsa AT. Vision Bollen AW, Parsa AT. Sarcoidosis of the pineal gland: of extradural foraminal tumors of the lumbar spine. salvage after resection of a giant meningioma in a an unusual presentation of neurosarcoidosis. J Neurosurg Spine 2009;10(1):46-50. patient with a loss in light perception. J Neurosurg J Neurooncol 2009;91(1):113-116. Lu DC, Wang V, Chou D. The use of allograft or 2009;110(1):109-111. autograft and expandable titanium cages for the treatment of vertebral osteomyelitis. Neurosurgery 2009;64(1):122-30. The Pediatric Brain Tumor Foundation of the United States (PBTFUS), based in Asheville, North Carolina, has awarded the UCSF John Fike PhD, professor of Praveen Mummaneni MD, associate Pediatric Brain Tumor Center a neurological surgery, has recently professor of neurological surgery, was 3-year, $1 million Institute Award for received two research grants from elected to Best Doctors in America pediatric brain tumor research. This the NIH: an R01 award for the study and was the honored guest of the grant will fund studies on stem cell “Radiation and oxidative stress: Taiwan Neurospinal Society in 2008. neurobiology, aberrant cell-signaling effects on neurogenesis” and an R21/ pathways, and the development Claudia Petritsch PhD, assistant R33 award for the study “Combined of siRNA molecules as therapeutic professor of neurological surgery, effects of traumatic brain injury and agents for pediatric brain tumors. has been granted a $30,000 ionizing irradiation on cellular and UCSF joins Duke University as one Individual Research Award from molecular determinates of cognitive of only two fully-funded PBTFUS the American Cancer Society function.” He has also been granted Institutes in the United States. for the project “Novel regulators a NASA Individual Research Award of neoplastic progenitor cell for the study “Use of a molecular transformation.” marker of learning and memory to New Faculty assess effects of 56Fe irradiation on R. Mark Richardson MD, PhD, hippocampal-dependent cognition resident in the Department of The Department of Neurological and neurogenesis.” Neurological Surgery, received Surgery at UCSF is pleased to a Kirschstein National Research announce the addition of several Jialing Liu PhD, associate profes- Service Award (NRSA) Postdoctoral new faculty members. Daniel Lim sor of neurological surgery, has Fellowship from the National MD, PhD, has become assistant been granted an American Heart Institute of Neurological Disorders professor of neurological surgery and Association Established Investigator and Stroke for the research project principal investigator of a laboratory Award for the project “The recovery “Effect of AADC gene transfer on studying neurogenesis and neural of post stroke mild cognitive impair- L-dopa induced dyskinesia in MPTP stem cells in the subventricular ment: an experimental model.” monkeys” (Principal Investigator: zone. He also has clinical interests She has also been given a VA Krystof Bankiewicz MD, PhD). in stereotactic neurosurgery and Research Career Scientist Award practices in the surgical movement James Waldron MD, resident in the for Biomedical Laboratory Research disorders program. After completing Department of Neurological Surgery, & Development. a fellowship in pediatric neurosurgery received the Integra Foundation Daniel Lim MD, PhD, assistant at the Hospital for Sick Children in 7 Award for his paper “Embolization professor of neurological surgery, Toronto, Kurtis Auguste MD joined of skull base meningiomas and and Arturo Alvarez-Buylla PhD, the Department as an associate feeding vessels arising from the Melanie Muss Endowed Chair and physician of neurological surgery and internal carotid artery: feasibility and professor of neurological surgery, director of pediatric epilepsy surgery. morbidity in a series of 262 consecu- have recently discovered that the Jennifer Clarke MD specializes in tive meningioma patients,” presented gene MLL1 is required for neural novel approaches to the treatment of at the 2009 AANS Annual Meeting. stem cells to differentiate into brain tumors in adult patients and is a neurons. Using a murine model, Isaac Yang MD, resident in the member of the Brain Tumor Research Lim and Alvarez-Buylla showed that Department of Neurological Surgery, Center, focusing on clinical trials for neural stem cells deficient in MLL1 received the Leksell Radiosurgery novel therapies and novel imaging were able to survive and differentiate Award from the AANS for the abstract methods of characterizing tumors into glia, but not neurons. “A systematic analysis of hearing and their response to treatment. and facial outcomes after Gamma Claudia Petritsch PhD has joined Lim DA, Huang YC, Swigut T, Mirick Knife radiosurgery for vestibular the Brain Tumor Research Center AL, Garcia-Verdugo JM, Wysocka J, schwannoma”, presented at the and established a laboratory Ernst P, Alvarez-Buylla A. Chromatin 2009 AANS Annual Meeting. He was studying cell division and remodelling factor Mll1 is essential also the recipient of a competitive differentiation of brain cancer stem for neurogenesis from postnatal UCSF Clinical and Translational cells. She is currently studying neural stem cells [published online Scientist Training Research Award regulators of asymmetric stem ahead of print February 11, 2009]. for his project “Hearing preservation cell division as potential tumor Nature. doi: 10.1038/nature07726. after Gamma Knife radiosurgery for suppressors and oncogenes vestibular schwannoma.” by utilizing knock out mice and orthotopic transplantation models. John Forsayeth PhD has become The first poly (L lactide) nanofibrous polymer graft implanted in a porcine carotid an adjunct professor of neurological surgery, and works with Krystof Bankiewicz MD, PhD in developing translational research programs focused on neuro-inflammation and the role of the immune system in Parkinson’s Disease. UCSF Department of Neurological Surgery Nonprofit Org 505 Parnassus Avenue, M779 U.S. Postage PAID San Francisco, CA 94143-0112 University of California San Francisco

selected recent publications from the department of neurological surgery

Barbaro NM, Quigg M, Broshek DK, Ward MM, Lamborn Vandenberg SR, Berger MS, James CD. Comparative Pirris SM, Dhall S, Mummaneni PV, Kanter AS. Minimally KR, Laxer KD, Larson DA, Dillon W, Verhey L, Garcia P, analyses of gene copy number and mRNA expression invasive approach to extraforaminal disc herniations Steiner L, Heck C, Kondziolka D, Beach R, in GBM tumors and GBM xenografts [published online at the lumbosacral junction using an operating Olivero W, Witt TC, Salanova V, Goodman R. A ahead of print January 12, 2009]. Neuro Oncol. doi: microscope: case series and review of the literature. multicenter, prospective pilot study of gamma knife 10.1215/15228517-2008-113. Neurosurg Focus 2008;25(2):E10. http://thejns.org/ radiosurgery for mesial temporal lobe epilepsy: seizure Hsu JY, Bourguignon LY, Adams CM, Peyrollier K, doi/full/10.3171/FOC/2008/25/8/E10. Accessed response, adverse events, and verbal memory. Zhang H, Fandel T, Cun CL, Werb Z, Noble-Haeusslein April 1, 2009. Ann Neurol 2009;65(2):167-175. LJ. Matrix metalloproteinase-9 facilitates glial scar Prados MD, Chang SM, Butowski N, DeBoer R, Butowski N, Chang SM, Junck L, Deangelis LM, Abrey formation in the injured spinal cord. J Neurosci Parvataneni R, Carliner H, Kabuubi P, Ayers-Ringler L, Fink K, Cloughesy T, Lamborn KR, Salazar AM, Prados 2008;28(50):13467-13477. J, Rabbitt J, Page M, Fedoroff A, Sneed PK, Berger MD. A phase II clinical trial of poly-ICLC with radiation Johnston LC, Eberling J, Pivirotto P, Hadaczek P, MS, McDermott MW, Parsa AT, Vandenberg S, James for adult patients with newly diagnosed supratentorial Federoff HJ, Forsayeth J, Bankiewicz K. Clinically CD, Lamborn KR, Stokoe D, Haas-Kogan DA. Phase II glioblastoma: a North American Brain Tumor Consortium relevant effects of AAV2-GDNF on the dopaminergic study of erlotinib plus temozolomide during and after (NABTC01-05). J Neurooncol 2009;91(2):175-182. nigrostriatal pathway in aged Rhesus monkeys radiation therapy in patients with newly diagnosed DeIpolyi AR, Yang I, Buckley A, Larson DA, Smith [published online ahead of print February 9, 2009]. glioblastoma multiforme or gliosarcoma. J Clin Oncol V, Barbaro NM, Cheung SW, Parsa AT. Fluctuating Hum Gene Ther. doi: 10.1089/hum.2008.137. 2009;27(4):579-584. response of a cystic vestibular schwannoma to Jun P, Hong C, Lal A, Wong JM, McDermott MW, Rosi S, Andres-Mach M, Fishman KM, Levy W, Ferguson radiosurgery. Neurosurgery 2008; 62(5):1164-1165. Bollen AW, Plass C, Held WA, Smiraglia DJ, Costello JF. RA, Fike JR. Cranial irradiation alters the behaviorally Dinca EB, Lu KV, Sarkaria JN, Pieper RO, Prados Epigenetic silencing of the kinase tumor suppressor induced immediate-early gene arc (activity-regulated MD, Haas-Kogan DA, Vandenberg SR, Berger WNK2 is tumor-type and tumor-grade specific cytoskeleton-associated protein). Cancer Res MS, James CD. p53 Small-molecule inhibitor [published online ahead of print December 9, 2008]. 2008;68(23):9763-9770. enhances temozolomide cytotoxic activity against Neuro Oncol. Sanchez-Mejia RO, McDermott MW, Tan J, Kim H, Young intracranial glioblastoma xenografts. Cancer Res doi: 10.1215/15228517-2008-096. WL, Lawton MT. Radiosurgery facilitates resection of 2008;68(24):10034-10039. Kim H, Hysi PG, Pawlikowska L, Poon A, Burchard brain arteriovenous malformations and reduces surgical Ferguson AR, Christensen RN, Gensel JC, Miller EG, Zaroff JG, Sidney S, Ko NU, Achrol AS, Lawton morbidity. Neurosurgery 2009;64(2)231-240. BA, Sun F, Beattie EC, Bresnahan JC, Beattie MS. MT, McCulloch CE, Kwok PY, Young WL: Common Wan JJ, Cohen MJ, Rosenthal G, Haitsma IK, Morabito Cell death after spinal cord injury is exacerbated by variants in interleukin-1-beta gene are associated DJ, Derugin N, Knudson MM, Manley GT. Refining rapid TNF alpha-induced trafficking of GluR2-lacking with intracranial hemorrhage and susceptibility to resuscitation strategies using tissue oxygen and AMPARs to the plasma membrane. J Neurosci brain arteriovenous malformation. Cerebrovascular perfusion monitoring in critical organ beds. J Trauma 2008;28(44):11391-11400. Diseases 2009;27(2):176-182. 2009;66(2):353-357. Hadaczek P, Forsayeth J, Mirek H, Munson K, Bringas Liu R, Solheim K, Polley MY, Lamborn KR, Page M, Wang Y, Bontempi B, Hong SM, Mehta K, Weinstein J, Pivirotto P, McBride J, Davidson B, Bankiewicz K. Fedoroff A, Rabbitt J, Butowski N, Prados M, Chang SM. PR, Abrams GM, Liu J. A comprehensive analysis of Transduction of nonhuman primate brain with adeno- Quality of life in low-grade glioma patients receiving gait impairment after experimental stroke and the associated virus serotype 1: vector trafficking and temozolomide. Neuro Oncol 2009;11(1):59-68. therapeutic effect of environmental enrichment in rats. immune response. Hum Gene Ther 2009;20(3): Pàez-Ribes M, Allen E, Hudock J, Takeda T, Okuyama J Cereb Blood Flow Metab 2008;28(12):1936-1950. 225-237. H, Viñals F, Inoue M, Bergers G, Hanahan D, Casanovas Hodgson JG, Yeh RF, Ray A, Wang NJ, Smirnov I, Yu M, O. Antiangiogenic therapy elicits malignant progression Editor: Ilona Garner ([email protected]) Hariono S, Silber J, Feiler HS, Gray JW, Spellman PT, of tumors to increased local invasion and distant Illustration: Kenneth Xavier Probst metastasis. Cancer Cell 2009;15(3):220-231. Photography: John Branscombe, Kaz Tsuruta For information on supporting the Department, contact the office of Development at 415/476-0506. Design & layout: Victoria Maier Magbilang