sign in sign up
<<
Home , Grant Imahara, Neural engineering, Surgery, UCSF Medical Center

Year In Review 2010 The Department of Neurological at UCSF

University of

Neurological Surgery

is a true example of how Contents will continue to improve our lives in the Tumor Center 2 years to come. California Center Among the many honors for Pituitary Disorders 6 given to our faculty in 2010, I would like to recognize Brain & Spinal Center 7 Dr. Nicholas Barbaro’s appointment as President of Adult Surgery 10 the Neurosurgical Society of America and Dr. Lawrence Epilepsy Research 11 Pitts’ appointment to Provost Movement Disorders and Executive Vice President Program 12 of Academic Affairs at the , Vascular Offi ce of the President. Program 16 I am exceedingly proud to have been chairman during Neurospinal Disorders a year marked by signifi cant Program 18 Letter from the Chair ingenuity and progress Pediatric towards understanding Since its inception in to train the future generation Neurological Surgery 22 and treating neurosurgical 1947, the Department of of academic neurosurgeons. disorders, and to work with Neurological Surgery at In this review, we highlight Pediatric Epilepsy Center 24 such a highly talented and UCSF has grown from a some of the major dedicated group of faculty UCSF Nerve Injury 24 division of the Department accomplishments and staff. of Surgery into one of the and fi ndings from the UCSF Neurological Surgery premier neurosurgical Department in 2010. Management Program 24 programs in the world. In In one of the more exciting 2010, we have neurosurgery developments, this month Center for Neural services at all major we launched the Center & Prostheses 25 in the Bay Area and we were for Neural Engineering and again ranked in the top fi ve Prostheses (CNEP, page 25) neurosurgery programs on – a collaboration between US News & World Report’s UCSF and UC Berkeley. annual list of Best Hospitals. Mitchel S. Berger, Department of While bionics that meld mind We also ranked fi rst in MD, FACS, FAANS Neurological Surgery and have long been funding for neurosurgery the stuff of fi ction, Kathleen M. Plant University of California, from the National Institutes this new program will build Distinguished Professor San Francisco of Health for the fi fth on current that and Chairman consecutive year. Our central 505 Parnassus Ave., are already allowing mission is to give the best Department of Room 779 M to move artifi cial limbs with care possible to our patients; Neurological Surgery thought. By bridging the gap San Francisco, CA to improve for between and Director, UCSF 94143-0112 neurosurgical disorders; and Center cognitive science, CNEP Phone: (415) 353-7500 Fax: (415) 353-2889 neurosurgery.ucsf.edu

Design & layout: Victoria Maier Magbilang Illustration: Kenneth Xavier Probst Photography: Noah Berger, John Branscombe, Susan Merrell, Kaz Tsuruta The Brain Tumor Center at UCSF The Brain Tumor Center at UCSF is one of the largest and most comprehensive programs for brain tumor treatment in the United States. It includes the Division of Neuro-, the Brain Tumor Research Center, and the Division of Translational Research.

2 Top: Susan Chang MD, Jennifer Clarke MD, Nicholas Butowski MD Bottom: 5-ALA causes tumor tissue to fl uoresce during surgery

Clinical Trial Highlights in the United States as an will be to create a virtual • The UCSF Helen Diller investigational new drug at a tissue bank to prospectively Family Comprehensive • The Department of handful of select institutions, identify subgroups Center has been Neurological Surgery is and UCSF is the only who will be candidates for chosen as one of fi ve cancer participating in a Phase II institution on the West Coast clinical trials done at time of centers in the United States study of 5-aminolevulinic to offer this cutting-edge tumor recurrence. to participate in the Merck acid (5-ALA) to enhance neurosurgical treatment. Oncology Collaborative • The Department of visualization and resection Trials Network (OncoNet), a • The Ben and Catherine Ivy Neurological Surgery is of malignant brain tumors. global clinical trials network Foundation has funded a currently offering a Phase The prodrug 5-ALA taken focusing on the development new clinical trials consortium II clinical trial for a novel orally before surgery causes of Merck drug and of fi ve institutions across the vaccine to treat , fl uorescent porphyrins to vaccine candidates being United States, led by Michael led by Andrew Parsa accumulate in tumor tissue investigated for the treatment Prados MD, director of the MD, PhD. Once a tumor and can be visualized under and prevention of cancer, Division of Translational is removed, a vaccine fl uorescent light during including brain tumors. surgery to identify tumor Research. The main is created from proteins cells and facilitate a more objective of the consortium specifi c to that tumor and Collaboration provides complete resection. will be to perform small, a heat- protein, and funding for infrastructure, enriched-patient clinical trials injected back into the patient fast-track access to It has previously only been for recurrent glioblastoma. over time. This prepares the compounds and drugs for used outside the United The goals will be to screen immune system to produce clinical trials, and a scientifi c States, and the European promising molecularly T cells that fi nd and kill new educational exchange. Every data show that it improves targeted agents and to cancerous cells with proteins year, the network will enroll extent of resection and validate drug distribution, matching those extracted approximately 1,200 patients leads to longer progression- pharmacokinetics, and from the tumor. in 30 to 40 investigator- free survival for patients. pharmacodynamics in tumor initiated or company- 5-ALA is now being tested tissue. Another objective sponsored trials. Faculty

Adult Clinical Oncolytic viral therapies; Nalin Gupta MD, PhD Russ Pieper PhD vascular biology of glioma Neuro-Oncology Pediatric brain tumors; Signal transduction; models cell-cell interactions of human gliomagenesis and Susan Chang MD Arturo Alvarez-Buylla PhD drug resistance Developmental neuroscience; Daphne Haas-Kogan MD Nicholas Butowski MD stem-cell neurobiology Apoptosis and genetic William Weiss MD, PhD Jennifer Clarke MD Krys Bankiewicz MD, PhD mutations; therapeutic Mouse models of irradiation enhancement tumors Michael Prados MD Convection drug-delivery systems; gene C. David James PhD Adult Brain Tumor John Wiencke PhD Surgery Mitchel S. Berger MD Molecular biology of CNS Biomarker development cancer; analysis of mutant and application in brain ; molecular Mitchel S. Berger MD epidermal growth factor tumor etiology genetic basis, biology, and Manish Aghi MD receptors in malignant therapy of brain tumors gliomas; rodent model Margaret Wrensch Edward Chang MD MPH, PhD Gabriele Bergers PhD testing of experimental Sandeep Kunwar MD therapies Genetic and molecular Angiogenesis; epidemiology of adult glioma Michael McDermott MD tumor invasion Andrew Parsa MD, PhD Andrew Parsa MD, PhD Shichun Zheng PhD Soonmee Cha MD Immunotherapy Molecular Perfusion magnetic Claudia Petritsch PhD resonance imaging Caroline Racine PhD Brain cancer stem cells; Joe Costello PhD asymmetric stem cell BTRC Laboratories division; novel tumor Functional genomics suppressor genes Manish Aghi MD, PhD

UCSF Neuro-Oncologists and prognostic markers Several new research studies of convection Have Highest Patient and improving classifi cation projects were initiated in enhanced delivery into the Satisfaction Scores and grading schemes for 2010, while many of our program’s overall focus on brain tumors. Dr. Phillips ongoing investigations . The Neuro-Oncology also directs the Molecular yielded signifi cant results. Partnering with Service was awarded the Morphology Laboratory, • California Institute for at UC Davis, P01 investigator UCSF Medical Center which is a core resource Regenerative Krystof Bankiewicz MD, PhD Pinnacle Award for the to assist investigators in (CIRM) Team Award: used convection-enhanced third consecutive year. This optimizing techniques for Funded by a $19 million delivery of nanoliposomal award recognizes the UCSF immunohistochemistry, grant from CIRM, the BTRC CPT-11 to treat dogs with medical service with the best molecular studies, and will lead studies with other spontaneous brain tumors, patient satisfaction scores for capture microdissection. outpatient care. California institutions to which are very similar to Brain Tumor genetically engineer stem tumors that arise in humans. Brain Tumor Center Research Center cells that deliver therapeutic CPT-11 was infused directly Welcomes New agents to selectively kill into the brain tumors via Neuropathologists Continuously funded by glioblastoma cells. If convection-enhanced grants from the National approved by the FDA, it will delivery, and its distribution Neuropathologists Joanna Institutes of Health (NIH) be tested fi rst in patients with was monitored in real time Phillips MD, PhD and Arie since 1972, the Brain Tumor recurrent glioblastoma. using intraoperative MRI. Perry MD have joined the Research Center (BTRC) Three years later, many of the • NIH Program Project Brain Tumor Center at at UCSF is internationally dogs’ tumors have shrunk or Grant (P01): The BTRC has UCSF, providing expertise recognized as a major stopped growing. There has been funded by a program in histopathological research and treatment been no evidence of toxicity project grant for 35 years. evaluation of CNS tumors. center for adults and children to normal brain tissue – a In 2007, BTRC investigators Their research interests lie with tumors of the brain and serious drawback of many took this program in a new in developing diagnostic spinal cord. other brain tumor therapies. direction by incorporating Manish Aghi MD, PhD gives a neurological examination

The therapy has been so • Specialized Program two or three tests, mostly successful in canines that of Research Excellence focusing on left-hemisphere UCSF investigators are (SPORE): UCSF is one of verbal tasks. Drs. Racine 4 planning to initiate a Phase I only four institutions in the and Butowski will administer trial for human patients with United States to receive tests to analyze cognition recurrent glioblastoma. funding from the National and behavior for the whole Cancer Institute for a SPORE brain, gaining insight into The exciting developments in brain tumor research. factors such depression, in this ongoing project Funding fi ve central projects, anxiety, and apathy, which were featured in the CBS5 the SPORE program also are often overlooked. HealthWatch story “Brain funds several Developmental Questionnaires will also be Cancer Treatment for Dogs Research and Career given to care givers, who Could Help Humans,” which Development Awards for are sometimes better able to aired in May 2010. junior investigators. provide accurate information Dickinson PJ, LeCouteur RA, regarding changes in function. Higgins RJ, Bringas JR, Larson RF, In 2010, a SPORE Yamashita Y, Krauze MT, Forsayeth Developmental Research Patients with newly J, Noble CO, Drummond DC, Award was granted to diagnosed glioblastoma will Kirpotin DB, Park JW, Berger MS, Bankiewicz KS. Canine spontaneous neuropsychologist Caroline be tested before surgery; glioma: a translational model system Racine PhD and neuro- after surgery but before for convection-enhanced delivery. oncologist Nicholas Butowski radiation and ; Neuro Oncol 2010;12(9):928-40. MD to focus on cognitive and four months after • The BTRC has received and behavioral effects of initiation of radiation and a T32 Training Grant in tumor and treatments. The chemotherapy. A parallel translational brain tumor main goal of the project Career Development Award research from the NIH. is to perform a more was granted to Janine Lupo The goal of this grant is to comprehensive battery of PhD in the Department provide high-quality training neuropsychological tests of to develop and development for future than has previously been imaging correlates related to researchers, and it will accomplished with brain cognitive function. support four postdoctoral tumor patients. Studies to fellows in BTRC laboratories. date have been confi ned to Caroline Racine PhD

Epigenomics to comprehensively map epigenomes of select Dr. Racine Talks about the Importance of The BTRC laboratory of human cells with signifi cant Neuropyschology in Care for Brain Tumor Patients Joseph Costello PhD has relevance to complex human recently discovered the Q: How will the neuro- to right hemisphere disease. methylation of a body psychological tests being tumors that have been of genes may infl uence Bernstein BE, Stamatoyannopoulos underappreciated in the JA, Costello JF, Ren B, Milosavljevic given in your SPORE research expression as much as literature. A, Meissner A, Kellis M, Marra MA, translate to clinical care? methylation of the promotor Beaudet AL, Ecker JR, Farnham PJ, Hirst M, Lander ES, Mikkelsen TS, A: Thinking and behavior Q: How do those changes region of a gene. Their fi ndings were published in Thomson JA. The NIH Roadmap are often rated as the effect patients? Epigenomics Mapping Consortium. the July 2010 issue of Nature. most important factors in Nat Biotechnol 2010;28(10):1045-8. A: Using the example of a patient’s quality of life. Maunakea AK, Nagarajan RP, Bilenky We want to know how the right hemisphere tumors, M, Ballinger TJ, D’Souza C, Fouse Brain Tumor Symposium various treatments we give there are times when SD, Johnson BE, Hong C, Nielsen Brings World-Renowned C, Zhao Y, Turecki G, Delaney A, affect these symptoms, and patients and their families Experts to UCSF have not been educated Varhol R, Thiessen N, Shchors K, ultimately quality of life. Heine VM, Rowitch DH, Xing X, On October 22, the UCSF about what effects the Fiore C, Schillebeeckx M, Jones Helen Diller Comprehensive Q: How does your experience tumor might have on their SJ, Haussler D, Marra MA, Hirst Cancer Center sponsored personality and thinking. M, Wang T, Costello JF. Conserved as a postdoctoral fellow in the a Brain Tumor Symposium By explaining that these role of intragenic DNA methylation UCSF Center for Memory and in regulating alternative promoters. at UCSF. The symposium changes are due to the Aging transfer to your work in Nature 2010;466(7303):253-7. brought international experts tumor location and/or the Brain Tumor Center? on brain tumor research, treatment, the “blame” is Dr. Costello and his including Richard Gilbertson A: There were a lot of transferred to the disease, colleagues are also working MD, PhD and Luis Parada lessons to be learned which can improve the cooperatively with other PhD, to the campus for a day by watching how the relationship between the Mapping Centers and the of lectures on brain tumor brain changes with patient and their family. Data Coordination Center biology and therapeutics. neurodegenerative (EDACC) funded by an As well, this information 5 like , can help their NIH Roadmap mechanism specifi cally about focality. providers select appropriate In brain tumor patients, interventions to improve there are often subtle the symptoms, which might changes in personality otherwise go unrecognized. Neurosurgeon Manish Aghi MD, PhD and ENT Ivan El-Sayed MD and behavior secondary perform minimally invasive base surgery to remove a brain tumor

Skull Base Surgery Program

Minimally invasive skull The most commonly base surgery has become used corridor for minimally an increasingly important invasive surgery is the aspect of skull base endonasal corridor. surgery at leading centers Through the endonasal throughout the country, corridor, neurosurgeons like UCSF. Minimally working with ENT invasive skull base can access of surgery is done through the anterior and central small corridors in which skull base, including an endoscope is used some , to provide a wide view, esthesioneuroblastomas, rendering these corridors pituitary adenomas, and the endonasal approach has rates of resections done as effective as the large chordomas. For chordomas been used by the team of through this approach, but corridors through which in particular, the change neurosurgeons at UCSF in results to date with minimally skull base surgery has has been dramatic – 21 patients over the past 5 invasive skull traditionally been done, whereas these tumors were years with minimal morbidity base surgery are encouraging without the morbidity typically resected through and comparable extent of and this program has associated with the aggressive transcranial resection. Long-term follow become an exciting larger exposures. operations a decade ago, up is underway to document development at UCSF. the long-term recurrence The California Center for Pituitary Disorders at UCSF Since it was founded in 2005, the California Center for Pituitary Disorders at UCSF has become one of the largest practices for diseases of the pituitary gland and hypothalamus in the nation, treating over 500 patients in 2010.

Faculty

Lewis Blevins Jr. MD

Sandeep Kunwar MD

Manish Aghi MD, PhD

6

• Investigators at the Tate MC, Jahangiri A, Blevins L, Sughrue M, McDermott M, California Center for Pituitary Kunwar S, Aghi MK. Infected Rathke Blevins LS. Extreme correction cleft : distinguishing factors of hyponatremia in a patient with Disorders have recently and factors predicting recurrence. intravenous conivaptan. J Clin reported the largest series Neurosurgery 2010;67(3):762-9. Neurosci 2010;17(10):1331-4. of patients with infected • Conivaptan is an arginine • Lewis Blevins Jr. MD, Rathke’s cleft cysts (RCC), vasopression receptor medical director of the describing how to manage antagonist administered California Center for Pituitary these patients. RCCs are to correct hyponatremia Disorders, was included benign sellar that Sandeep Kunwar MD, associated with SIADH. in Marin Magazine’s list are generally asymptomatic Surgical Director and While overcorrection of of Best Doctors and was but sometimes warrant Lewis Blevins Jr. MD, hyponatremia is often a recently interviewed on the Medical Director transsphenoidal drainage. concern for , the topic of for the Their review found that California Center for Pituitary E! Entertainment TV show suspected RCC , Disorders has published “Born Different: Unbelievable regardless of culture results, the fi rst report of its use in Medical Conditions.” is a strong predictor of a neurosurgery unit, outside recurrence and may warrant Dr. Blevins was also of an intensive care setting. treatment. Among interviewed by Patient Power The report concluded that patients with suspected on the topic of pituitary the drug is safe and effective, , but negative tumors. The show recording but patients must be cultures, the recurrence rate can be heard at: www. monitored closely. was relatively high at 44%. ucsfhealth.org/common/ audio/blevins020910.mp3 Brain and Spinal Injury Center Based at San Francisco General , the UCSF Brain and Spinal Injury Center (BASIC) is an internationally-recognized program for basic science research and clinical care for neurotrauma.

The goals of BASIC are to: Grand Opportunity decades of research and Investigators at BASIC are over two dozen clinical leading a study funded • Translate basic Grant – Transforming trials, research into the by a $4.1 million Grand neuroscience into Care of Traumatic mechanisms of traumatic Opportunity Grant, a part clinical practice Brain Injury brain injury has not translated of the American Recovery • Understand brain and is into effective treatments. and Reinvestment Act, to one of the greatest unmet A substantial part of the overhaul and standardize • Train the next generation needs in – problem is that the current classifi cation for traumatic of neurotrauma clinicians approximately 1.7 million classifi cation system does brain injury on a large scale. and scientists Americans sustain a not take into account the The multi-center study, led traumatic brain injury each specifi c pathophysiology of • Educate the public on year and 5.3 million have a each injury – it only divides neurotrauma research chronic resulting them into the categories and clinical care from their . Despite “mild, moderate, and severe.”

7 Faculty

Neurotrauma, Jacqueline Bresnahan PhD Linda Noble- Haeusslein PhD San Francisco Central nervous General Hospital system repair Traumatic brain and spinal cord injury Geoffrey Manley MD, PhD Adam Ferguson PhD S. Scott Panter PhD Michael Huang MD Traumatic brain and spinal cord injury Cellular injury following Nicholas Phan MD stroke and hemoglobin- John Fike PhD based neurological injury Shirley Stiver MD, PhD Neurogenesis and Susanna Rosi PhD Vincent Wang MD, PhD traumatic brain injury Chronic neuroinfl ammation; BASIC Laboratories Jialing Liu PhD learning and memory Neurogenesis and functional Michael Beattie PhD Shirley Stiver MD, PhD recovery after stroke Central nervous Cerebral angiogenesis system repair Geoffrey Manley MD, PhD in neurological injury Basic, translational, and and disease clinical traumatic brain injury research by principal investigator and Cohen MJ, Grossman AD, Morabito works with pre-hospital BASIC Initiates Study of BASIC Co-Director Geoffrey D, Knudson MM, Butte AJ, Manley emergency medical services, GT. Identifi cation of complex Combined Head and Manley MD, PhD, will test the SF Department of Public metabolic states in critically injured Spinal Cord Injury and refi ne standards for data patients using bioinformatics cluster Health, and all ambulance collection and use advanced analysis. Crit Care 2010;14(1):R10. destination hospitals in San Researchers at BASIC, led neuroimaging methods Francisco to coordinate these by Co-Director Michael to fi nd better approaches San Francisco studies. Current trials include: Beattie PhD, have been for traumatic brain injury Neurological awarded over $1.1 million by • RAMPART – a prehospital classifi cation and outcomes. the Department of Defense Emergencies clinical trial of status The study will follow 600 Spinal Cord Injury Research Treatment Trials epilepticus treatment patients and 400 patients Network Program to develop have already signed on in the • ALIAS2 – a trial for preclinical models of cases fi rst six months of enrollment. The NIH-funded San acute ischemic stroke of combined head and spinal 8 Francisco Neurological neuroprotection cord injury. The BASIC team Whyte J, Vasterling JJ, Manley GT. Emergencies Treatment is partnering with Graham Common data elements for research • PROTECT III – a study Trials (SF-NETT) network Creasy at VA Health Service on traumatic brain injury and to test progesterone as psychological health: current status was created to provide Palo Alto to examine the neuroprotection in and future development. Arch Phys infrastructure throughout San clinical condition of patients Med Rehabil, In Press. traumatic brain injury Francisco that allows BASIC to design better animal Chun KA, Manley GA, Stiver SI, investigators to conduct • POINT – a trial for acute models of combined head Aiken AH, Phan N, Wang V, Meeker Phase III clinical trials in a intervention for transient and spinal cord injury. M, Cheng SC, Gean AD, Wintermark wide range of neurological ischemic attacks M. Interobserver variability in the assessment of CT imaging emergencies including features of traumatic brain injury. J status epilepticus, stroke, Neurotrauma 2010;27(2):325-30. and neurotrauma. SF-NETT Geoffrey Manley MD, PhD and MythBusters host Grant Imahara

UCSF Neurosurgery term effects of brain injury NIAID Program Collaborates with from concussions or high- in Radiation the National Football impact collisions. Combined Injury League on New Bench Research for The National Institute of Head Injury Guidelines Spinal Cord Injury and Infectious In 2010, the Department Diseases (NIAID) of the Adam Ferguson PhD has of Neurological Surgery NIH, initiated a program in been awarded a total of at UCSF has become 2008 focused on Medical $1.8 million by the NIH actively involved at all Countermeasures Against in the form of two R01 levels of the concussion Radiological and Nuclear research awards for the debate that is taking place Threats. Phased Innovation studies: “Metaplasticity and within the National Football Awards (R21/R33) were Recovery after Spinal Cord League (NFL). In 2010, fi rst given in 2008 and the Injury: Cellular Mechanisms” Mitchel Berger MD, chair only grant focused on the and “Bioinformatics for of Neurological Surgery central nervous system Translational Spinal at UCSF, was named to was awarded to BASIC Cord Injury.” the NFL Head, Neck, and researcher John R. Fike Spine Committee, focusing MythBusters PhD, who is investigating the particularly on retired players’ Features BASIC combined effects of ionizing issues. The main goal of the irradiation and traumatic Co-Director Geoffrey brain injury. After successfully committee is to draft new Manley MD, PhD return-to-play guidelines and completing the R21 element, examine the consequences The Discovery Channel show Dr. Fike was awarded an of repetitive head injury and MythBusters consulted Dr. R33 in 2010 for the project concussion. Manley for an episode that “Combined Radiation and tackled the question: “Do we Traumatic Injury Affects Dr. Manley also serves on really only use 10 percent Hippocampal Structure and the AAN Sports Concussion 9 of our brain?” Show host Function.” The total award Guidelines Committee and Grant Imahara met with Dr. is for $1 million. Dr. Fike’s was recently interviewed on Manley to discuss the battery combined injury studies are ESPN’s Outside the Lines, of tests MythBusters would done in conjunction with where he explained that need to perform to debunk BASIC investigator Susanna more research, especially this myth. The episode aired Rosi PhD, and they are prospective, longitudinal on October 27, 2010. complementary to his earlier studies that study players NASA-funded studies on over time, is needed before trauma and irradiation in the we can understand the long- space environment. Traumatic brain injury is primarily classifi ed by severity and not by pathology, making standardization for clinical trials diffi cult. All of the injuries below are considered “severe,” yet may require vastly different treatments. With funding from a federal Grand Opportunity grant, BASIC researchers are overhauling classifi cation schemes for traumatic brain injury. Nicholas Barbaro MD

Adult Epilepsy Surgery

Epilepsy Surgery Edward Chang MD ROSE Trial For more information or to enroll a patient, contact Erica Joins Epilepsy Team The Department of Nicholas Barbaro MD Terry at (415) 476-2180. In 2010, the surgical epilepsy Neurological Surgery has Edward Chang MD begun enrolling patients in Barbaro NM, Quigg M, Broshek DK, team at UCSF was joined et al. A multicenter, prospective pilot the or Open 10 Paul Larson MD by neurosurgeon Edward study of Gamma radiosurgery Chang MD, who has clinical Surgery for Epilepsy (ROSE) for mesial : Epilepsy Research expertise in surgical therapies trial – a Phase III, multicenter, seizure response, adverse events, Laboratories for intractable epilepsy. randomized trial of Gamma and verbal memory. Ann Neurol 2009; 65(2):167-75. A former resident in the Knife radiosurgery for Arturo Alvarez- Department of Neurological mesial temporal sclerosis. Buylla PhD DBS for Epilepsy Surgery, Dr. Chang The NIH-funded study is Not Approved Scott Baraban PhD specializes in advanced led by Nicholas Barbaro brain mapping methods and MD, director of the surgical The U.S. FDA has yet Faculty has research interests in epilepsy program at UCSF, to approve deep brain the cortical mechanisms of and will determine if Gamma stimulation (DBS) as a language function. Together Knife radiosurgery can treatment for epilepsy, with Paul Larson MD, he is provide a noninvasive, viable despite the results of expanding UCSF’s surgical alternative to open surgery. Medtronic Inc.’s SANTE epilepsy program at the San There are currently 13 study (Stimulation of the Anterior Francisco Veterans Affairs sites in the United States, Nucleus of the Thalamus in Medical Center (SFVAMC), and three more will be Epilepsy) clinical trial, which which is a National Center opening in Canada and the demonstrated some benefi t of Excellence for Epilepsy. U.K. in 2011. for patients. The European Agency approved Neurological Surgery The pilot study for the ROSE DBS for intractable epilepsy faculty at SFVAMC take a trial, published in 2009, in September 2010. multidisciplinary approach showed that radiosurgery to treating patients and work for unilateral temporal lobe Fisher R, Salanova V, Witt T, et al. Electrical stimulation of the anterior closely with neurologist Karen epilepsy results in seizure Parko MD and her team, who nucleus of thalamus for treatment remission rates comparable of refractory epilepsy. Epilepsia specialize in the diagnosis with those reported 2010;51(5):899-908. and treatment of epilepsy. previously for open surgery. Epilepsy Research

Progenitor Cell • California Institute of Investigator: Scott Baraban): of spontaneous epilepsy Transplantation for The grant proposals for in a zebrafi sh. Dr. Baraban Epilepsy Early Translational II Award these awards were scored and his colleagues have “Inhibitory Nerve Cell in the top two percent by shown that fi sh with a Epileptic seizures result Precursors: Dosing, Safety NIH reviewers. In these mutant form of the gene E3 from uncontrolled electrical and Effi cacy” (Principal studies, mouse embryonic ubiquitan ligase (mind bomb signaling in the brain, and Investigator: Arturo Alvarez- progenitor cells from the mutants) exhibit grossly failure of interneurons to Buylla): This award will fund MGE, which can differentiate abnormal brain structure inhibit excitatory circuits research to develop a human into interneurons, will be during development and may play a role in the onset embryonic stem cell (hESC) transplanted into the spontaneous epilepsy. of seizures. In preclinical line from progenitors in the of adult mice with temporal Previously, epilepsy models studies, the laboratories of medial ganglionic eminence lobe epilepsy and of adult in zebrafi sh were achieved 11 Scott Baraban PhD, Arturo (MGE) that can differentiate mice with a genetic form of by exposing the fi sh to Alvarez-Buylla PhD, and into interneurons. These epilepsy (Dlx1 mutant mice). convulsant drugs. John Rubenstein MD, PhD are expected The goal will be to determine To date, microarray analyses transplanted adult mouse to inhibit hyperactive if interneurons arising from of the mind bomb mutants progenitor cells into a mouse neural circuits in a mouse embryonic MGE progenitor have shown down regulation model of epilepsy, where model of epilepsy. UCSF cells can inhibit seizure of several genes necessary they differentiated into investigators will implant activity caused by these for GABA-mediated interneurons. Transplanted the human-derived cells distinct forms of epilepsy. signaling, which adds to a interneurons were able to into mice to determine the Baraban SC, Southwell DG, growing body of evidence integrate into the neocortex dose needed to increase Estrada RC, Jones DL, Sebe JY, indicating that a decrease and produce GABA – an inhibition and to examine Alfaro-Cervello C, García-Verdugo in GABA plays a role in the inhibitory potential effects on the host JM, Rubenstein JL, Alvarez- Buylla A. Reduction of seizures by onset of epileptic seizures. – that blocked spontaneous neurons. This project will also transplantation of cortical GABAergic The new model will allow for seizures in the mice. involve developing assays interneuron precursors into Kv1.1 high-throughput screening to determine the stages mutant mice. Proc Natl Acad Sci In 2010, several grants were of potential targets involved of hESC differentiation USA 2009;106(36):15472-7. awarded to Department in epilepsy, as well as new into MGE cells prior to of Neurological Surgery A New Model of therapeutic agents. investigators to build on the implantation. Spontaneous Epilepsy Horotopan GA, Dinday MT, Baraban breakthroughs of this work • NIH R01 “An Interneuron- in Zebrafi sh SC. Spontaneous seizures and and examine the potential based Cell Therapy For altered gene expression in GABA for developing a human Epilepsy” & NIH R21 The laboratory of Scott signaling pathways in a mind progenitor cell therapy Baraban PhD has bomb mutant zebrafi sh. J Neurosci “Interneurons and Epilepsy in 2010;30(41)13718-28. for epilepsy: Dlx1 Mutant Mice” (Principal developed the fi rst model

Left: Zebrafi sh provide models of epilepsy for research. Center: Scott Baraban PhD Right: Mind bomb mutant zebrafi sh have abnormal brain development patterns and spontaneous epileptic seizures. Movement Disorders Program The Department of Neurological Surgery at UCSF is home to the largest movement disorders surgery practice in the Western United States – treating over 1000 patients since 1998 for debilitating disorders such as Parkinson’s disease, essential tremor, , and dystonia. Our research is aimed at better understanding the fundamental mechanisms of these disorders and fi nding new therapies that can be moved to clinical trials. Our faculty are at the forefront of new techniques for surgical treatment, gene transfer, and drug-delivery methodologies that are changing the face of clinical care for movement disorders.

ClearPoint System they can have the surgery and MR coils specifi cally (neurturin) for mid-stage for DBS Approved under general , designed to provide optimal Parkinson’s disease. Unlike by the FDA rather than in the awake imaging during surgery, previous trials of this gene state required for the eliminating the need for therapy that targeted the In June 2010, the FDA standard surgical method a stereotactic frame and striatum, the current trial approved ClearPoint – for DBS implantation. physiological recording. The is injecting the gene into a new system for performing new software environment the nigra compacta. This is ClearPoint was developed (DBS) streams data from any the area of the brain where by UCSF neurosurgeons for movement disorders manufacturer’s 1.5T MRI cell bodies of degenerating Paul Larson MD and Philip using interventional MRI. scanner and guides the dopamine cells exist, Starr MD, PhD together with The system is used inside surgeon through the potentially making it a better MR physicist Alastair Martin 12 the scanner itself and has implantation procedure using delivery site for the therapy. PhD and the medical device substantially shortened a specially designed graphical The fi rst patient in this new company SurgiVision. It operating time for DBS interface. The scientifi c article nation-wide study was includes an MRI-compatible cases. The technique is describing the technique operated on at UCSF in skull-mounted aiming device attractive to patients because of DBS insertion using October 2010. interventional MRI was featured on the cover of the Verdict Reached on March 2010 issue of Journal Region of Brain to of Neurosurgery. Target with DBS for Starr PA, Martin AJ, Ostrem JL, Parkinson’s disease Talke P, Levesque N, Larson PS. Subthalamic nucleus deep brain In June 2010, the largest stimulator placement using high-fi eld study of DBS for Parkinson’s interventional magnetic resonance disease ever performed imaging and a skull-mounted was published in the New aiming device: technique and England Journal of Medicine. application accuracy. J Neurosurg 2010;112(3):479-90. Although DBS is the gold standard for the surgical New Clinical Trial of AAV- care of movement disorders, Neuturin for Parkinson’s there has been continued Disease debate over which area of the brain is best to stimulate UCSF is participating in – the globus pallidis interna an eight-center, Phase II (GPi) or the subthalamic trial of a gene encoding a nucleus (STN). The trial was dopaminergic growth factor carried out at seven VA and

The ClearPoint system allows DBS for movement disorders to be performed using interventional MRI. The interventional MRI suite at UCSF Medical Center

Faculty six university hospitals and a prospective pilot trial DBS as a future treatment for randomized 300 patients of a novel approach to patients with severe tinnitus. Movement Disorders (including 80 at UCSF) to the treatment of cervical The work was also featured Surgery receive DBS in either the GPi dystonia: DBS of the in the October issue of or STN. subthalamic nucleus. The Discover magazine. Philip A. Starr MD, PhD technique is shown to The results showed that Cheung SW, Larson PS. Tinnitus Nicholas Barbaro MD reduce the incidence of stimulation of GPi and STN modulation by deep brain debilitating adverse effects, stimulation in locus of caudate were equal in motor benefi t, Edward Chang MD in comparison with prior neurons (area LC). Neuroscience but GPi was shown to be 2010;169(4):1768-78. studies utilizing different Paul S. Larson MD slightly safer for patients with brain targets. Zimmer C. “Ringing in the ears” impaired cognitive function actually goes much deeper than Daniel A. Lim MD, PhD 13 or depression. These fi ndings DBS to Modulate Tinnitus that. Discover. October 27, 2010. are now changing the way http://discovermagazine.com/2010/ Movement Disorders DBS surgery is performed Recently featured on oct/26-ringing-in-the-ears-goes- much-deeper. Research Laboratories for Parkinson’s patients with the September cover of those symptoms and leading Neuroscience, Paul Larson Pathophysiology Studies Krystof Bankiewicz MD, PhD doctors to consider factors MD, Chief of Neurosurgery of Movement Disorders other than motor function at San Francisco Veterans Gene therapy for when deciding what area of Affairs Medical Center, and Dr. Starr has received an Parkinson’s disease the brain to target. colleague Steven Cheung R01 award from the NIH to MD in the UCSF Department investigate cortical and basal Follett KA, Weaver FM, Stern M, Paul S. Larson MD Hur K, Harris CL, Luo P, Marks WJ of Otolaryngology have ganglia local fi eld potentials Jr, Rothlind J, Sagher O, Moy C, shown that using deep in movement disorders. By Neurotransplantation Pahwa R, Burchiel K, Hogarth P, Lai brain stimulation to acutely studying cortical physiology strategies for Parkinson’s EC, Duda JE, Holloway K, Samii A, stimulate the caudate in patients with Parkinson’s disease; intraoperative Horn S, Bronstein JM, Stoner G, disease, primary dystonia, neuroimaging Starr PA, Simpson R, Baltuch G, De nucleus in patients with Salles A, Huang GD, Reda DJ; CSP Parkinson’s disease and and essential tremor, as well Philip A. Starr MD, PhD 468 Study Group. Pallidal versus tinnitus can result in a subjects without movement subthalamic deep-brain stimulation decrease in tinnitus loudness disorders, Dr. Starr and Surgical treatment of for Parkinson’s disease. N Engl J perception. The caudate postdoctoral fellow Coralie Med 2010;362(22):2077-91. movement disorders; nucleus is not considered DeHemptinne, are testing the basal ganglia physiology Novel Brain Target to be part of the traditional theory that the symptoms in movement disorders for the Treatment of auditory pathway, and this of movement disorders are Cervical Dystonia is the fi rst work to suggest produced by pathological that the caudate is involved oscillations in the circuit Philip Starr MD, PhD, co- in auditory perception. The connecting the cortex and director of the Functional fi ndings from this initial study basal ganglia. Neurosurgery Program, will likely pave the way for and UCSF neurologist Jill new studies to investigate Ostrem MD have completed Intaoperative Su X, Kells AP, Aguilar Salegio EA, Rating Scale scores and Richardson RM, Hadaczek P, Beyer persistent gene expression Image-Guided Delivery J, Bringas J, Pivirotto P, Forsayeth was demonstrated on Direct, intraoperative delivery J, Bankiewicz KS. Real-time MR imaging with Gadoteridol predicts neuroimaging. A Phase II trial of genes or drugs into the distribution of transgenes after using the new image-guided brain has been a major area convection-enhanced delivery of delivery system developed of interest for researchers of adeno-associated virus (AAV)2 by the Bankiewicz laboratory vectors. Mol Ther 2010;18(8):1490-5. neurodegenerative disorders will begin in 2011 at UCSF. and brain . However, until now, it was diffi cult to Upcoming Clinical Trials • UCSF will initiate a Phase determine how much of the with Intraoperative I trial of AAV2-AADC using agent reached the target and Image-Guided Delivery intraoperative infusion in children with AADC how much of it may have • With funding from defi ciency. AADC defi ciency leaked into the cerebrospinal the National Institute of is an extremely rare pediatric fl uid or gone to other sites in Neurological Disorders disorder in which children the brain. (NINDS), a Phase I clinical are unable to form dopamine trial of image-guided Kyrstof Bankiewicz MD, and serotonin, resulting in PhD and members of his delivery of glial cell-derived

14

The ClearPoint software allows the surgeon to view the MR images in different orientations to guide DBS electrode implantation.

laboratory have designed neurotrophic factor (GDNF) severe symptoms, similar to a novel system to visualize for Parkinson’s disease is in those seen in Parkinson’s delivery of agents into the development. This will be the disease, or death. The brain in real time using fi rst trial for image-guided study will be funded by the MRI. Over 10 years in delivery of viral vectors in NIH Offi ce of Rare Disease development, it is now being humans. Research in their continued used in a variety of clinical efforts to support research • In a Phase I clinical trial applications, including the for orphan diseases. for Parkinson’s disease fi rst clinical trials of image- performed at UCSF last year, guided intraoperative delivery Gene Transfer in the gene for the enzyme of gene therapy, being Primate Models of AADC, which converts performed at UCSF. L-dopa into dopamine, was Parkinson’s Disease – Funding to validate image- delivered via convection Breakthroughs from the guided delivery as the enhanced delivery to 10 Bankiewicz Laboratory method of choice for gene patients. All patients had • A study demonstrating delivery was provided by the improvement in off-label that high GDNF expression Michael J. Fox Foundation Unifi ed Parkinson’s Disease promotes restoration of the and the NIH. Neurological Surgery for Obsessive Compulsive Disorder

The fi rst surgery to treat severe, medically refractory patients for this cutting-edge severe obsessive compulsive obsessive compulsive therapy are being evaluated disorder with deep brain disorder. Neurosurgeon Paul in the UCSF Department stimulation at UCSF was Larson MD and psychiatrist of under the performed in October Maria Pease MD performed direction of Dr. Pease and her 2010. The treatment was the procedure on a woman colleague Dr. Carol Mathews, FDA approved under from the Bay Area with Director of UCSF’s Obsessive a special humanitarian both severe OCD and Compulsive Disorders Clinic. device exemption last major depression. Potential year for patients with

dopaminergic system in a primate brain, primates projections transport the Designed primate model of advanced infused with AAV2-human vector to the cortex via Transcription Factors Parkinson’s disease may L-amino acid decarboxylase an anterograde transport and Parkinson’s Disease provide impetus for clinical (hAADC) to treat Parkinson’s mechanism. The laboratory studies with new drug- disease exhibit strong is currently building on these The Bankiewicz group has delivery methodologies in expression of the gene and novel fi ndings by mapping been working with Sangamo patients with advanced restoration of AADC activity the thalamus to predict the BioSciences, Inc. to develop stages of the disease. (leading to restored normal corresponding regions of the an artifi cial protein switch GDNF has previously only response to levodopa) eight cortex. By understanding that can specifi cally turn 15 shown a neuroprotective years after infusion. how to direct gene therapies on the gene for a growth factor, GDNF, which shows effect in preclinical models Hadaczek P, Eberling JL, to the appropriate part of the because it was given Pivirotto P, Bringas J, Forsayeth cortex, it might be possible promise in restoring function prior to the appearance J, Bankiewicz KS. Eight years of to target diseases of the in Parkinson’s disease. of extensive nigrostriatal clinical improvement in MPTP- cortex much more precisely. They have shown that a lesioned primates after gene therapy viral vector containing the degeneration, which is with AAV2-hAADC. Mol Ther Salegio EA, Kells AP, Richardson RM, gene switch could turn on a hallmark of patients 2010;18(8):1458-61. Hadaczek P, Forsayeth J, Bringas J, with Parkinson’s disease. Sardi SP, Passini MA, Shihabuddin the endogenous GDNF This study is important Axonal-Mediated LS, Cheng SH, Fiandaca MS, gene when injected into rat Bankiewicz KS. Magnetic resonance striatum. More importantly, because it established the Delivery of Genes imaging-guided delivery of adeno- they showed that this likely permanent nature of to Cortex associated virus type 2 to the neurological gene therapy primate brain for the treatment of approach could substantially A new method has been and its inherent safety. lysosomal storage disorders. Hum retard the actions of a toxin identifi ed for axonal- Gene Ther 2010;21(9):1093-103. that produces Parkinson’s Kells AP, Eberling J, Su X, Pivirotto P, mediated delivery of gene Bringas J, Hadaczek P, Narrow WC, Kells AP, Hadaczek P, Yin D, symptoms in rats. Recently, Bowers WJ, Federoff HJ, Forsayeth therapies to discrete regions Bringas J, Varenika V, Forsayeth the Michael J. Fox J, Bankiewicz KS. Regeneration of of the cortex. Dr. Bankiewicz, J, Bankiewicz KS. Effi cient gene Foundation awarded the therapy-based method for the the MPTP-lesioned dopaminergic together with John Forsayeth team, lead by Steven Zhang system after convection-enhanced delivery of therapeutics to primate PhD and their colleagues, PhD, a development grant to delivery of AAV2-GDNF. J Neurosci cortex. Proc Natl Acad Sci USA have shown that viral-vector 2010;30(28):9567-77. 2009;106(7):2407-11. further improve the therapy delivery to specifi c regions before initiating clinical study • In the longest known Varenika V, Kells AP, Valles F, of the cortex is possible Hadaczek P, Forsayeth J, Bankiewicz in Parkinson’s patients. study of AAV-mediated gene by injecting the vector into KS. Controlled dissemination of AAV expression in nonhuman the thalamus, where axonal vectors in the primate brain. Prog Brain Res 2009;175:163-72. Vascular Neurosurgery Program The Vascular Neurosurgery Program at UCSF specializes in treating brain , subarachnoid hemorrhage, arteriovenous malformations, cavernous malformations, stroke, and intracranial hemorrhage.

Above: Seven Aneurysms: During the past year, • The UCSF Cerebrovascular from extracranial- Tenets and Techniques for members of the Vascular Research Center developed intracranial bypass to Clipping, by Michael Lawton Neurosurgery Program a new grading scale for intracranial-intracranial MD, was published in 2010 and details common aneurysms have produced several arteriovenous malformations bypass over a decade. treated by neurosurgeons. notable publications (AVMs), which supplements Sanai N, Zador Z, Lawton MT. Below: Michael Lawton MD aimed at advancing the Spetzler-Martin grading Bypass surgery for complex brain uses advanced microsurgical care and knowledge of scale and is used to identify aneurysms: An assessment of techniques to perform a bypass cerebrovascular disorders: patients with AVMs who are intracranial-intracranial bypass. Neurosurgery 2009;65(4):670-83. for ischemia. good surgical candidates. • Seven Aneurysms: Tenets While the Spetzler-Martin • The UCSF experience and Techniques for Clipping scale evaluates AVM site, with previously coiled is a single-author text venous drainage, and aneurysms demonstrated written by Chief of Vascular eloquence, the UCSF scale that aneurysms that recur Neurosurgery, Michael takes into account AVM after coiling can be clipped Lawton MD. Summarizing , age of patient, and and often bypassed. Dr. Lawton’s experience AVM diffuseness. with 2500 aneurysms, this Waldron JS, Halbach VV, Lawton MT. Microsurgical management of reference book contains Lawton MT, Kim H, McCulloch 16 incompletely coiled and recurrent 450 illustrations and covers CE, Mikhak B, Young WL. A supplementary grading scale aneurysms: Trends, techniques, techniques and strategies for selecting patients with brain and observations on coil extrusion. for common aneurysms arteriovenous malformations Neurosurgery 2009;64 (ONS Suppl that neurosurgeons will be for surgery. Neurosurgery 2):301-17. treating in the future. 2010;60(4):702-13. • UCSF neurosurgeons Lawton MT. Seven Aneurysms: • A large intracranial bypass reported two variations Tenets and Techniques for Clipping. series was published of surgical approach that New York, NY: Thieme; 2010. describing the advancement improve surgical access and exposure to cavernous Vascular Neurosurgery Cerebrovascular Jialing Liu PhD William Young MD Research Laboratories Neurogenesis and functional Pathophysiology of Michael Lawton MD recovery after stroke arteriovenous Michael Lawton MD Michael Huang MD malformations; Pathophysiology of S. Scott Panter PhD hemodynamics of Faculty Michael McDermott MD arteriovenous malformation; Animal models of stroke and aneurysms; predictors (Gamma Knife radiosurgery) hemodynamics of traumatic brain injury of brain hemorrhage in aneurysms; radiation- patients with AVMs induced arteriopathy

malformations and AVMs, with outcomes over a decade Vascular Neurosurgery Cases at UCSF in 2010 making these procedures at UCSF was published safer for patients. to aid neurosurgeons in Arteriorvenous malformations (49) Sanai N, Mirzadeh Z, Lawton MT. choosing the best approach Supracerebellar-supratrochlear for each case. Cavernous malformations (46) and infratentorial-infratrochlear Chang EF, Gabriel RA, Potts Aneurysms (265) approaches: Gravity-dependent MB, Berger MS, Lawton MT. variations of the lateral approach Carotid atherosclerotic disease (10) Supratentorial cavernous over the cerebellum. Neurosurgery malformations in eloquent and deep 2010;66 (ONS 2): 264-74. locations: Surgical approaches • A comparison of various and outcomes [published surgical approaches to online ahead of print July 2, 2010]. Journal Neurosurg. doi: cavernous malformations 10.3171/2010.5.JNS091159 Neurospinal Disorders Program The Neurospinal Disorders Program provides comprehensive treatment for all affecting the spine and peripheral nerves. The program is based in the Department of Neurological Surgery and is a component of the UCSF Spine Center.

Christopher Ames MD Philip Weinstein MD Nicholas Barbaro MD

Praveen Mumaneni MD Dean Chou MD Faculty

Multi-Center for a minimum of two years, tumors or deformity, who Very few animal models that Collaborations the team will gather valuable are at increased risk for accurately mimic an elderly data on outcomes following during surgery. spinal cord exist, even though 18 All members of the surgery for these disorders. Each patient is treated by a this population is generally at Neurospinal Disorders hospitalist and a nutritionist greater risk for injury. • The Scoliosis Research Program are also members of who optimizes the patient’s Society — a non-profi t collaborative research teams diet prior to surgery. Surgery Spinal Deformity organization made up of that work to gather high- is performed by Dr. Ames in Patients with physicians and health quality data and perform and orthopaedic surgeon professionals dedicated to Parkinson’s Disease prospective, longitudinal Vedat Deviren MD, who education, research, and Movement disorders and studies on patients with operate simultaneously on treatment of spinal deformity. spine care specialists at spinal disorders. each case. Preliminary data Dr. Ames was recently UCSF work together closely has shown that blood loss • The International Spine named to the Morbidity and to care for patients with during these is Study Group (ISSG) — Mortality Committee, which both Parkinson’s disease less than half of what is lost an international research has examined complications and spinal deformity. during a surgery performed group composed of associated with pediatric Although there is little by a single surgeon (at leading physicians in scoliosis surgery. guidance for management, spinal deformity surgery. UCSF), and operating time is Reames DL, Smith JS, Fu KM, et this issue is becoming Christopher Ames MD, co- 2.5 hours shorter. al. Complications in the Surgical increasingly relevant with a director of the Neurospinal Treatment of 19,360 Cases of Cloyd JM, Acosta FL Jr, Cloyd growing elderly population Disorders Program and Pediatric Scoliosis: A Review of the C, Ames CP. Effects of age on of Parkinson’s patients. Scoliosis Research Society Database perioperative complications of director of spinal deformity, Spinal deformity can be a is currently involved in [published online ahead of print Oct extensive multilevel thoracolumbar 28 2010]. Spine (Phila Pa 1976). doi: surgery. J Neurosurg consequence of Parkinson’s an ISSG study examining 10.1097/BRS.0b013e3181f3a326. Spine 2010;12(4):402-8. disease, and a recent study clinical outcomes for patients at UCSF demonstrated receiving lumbar . Improving Spinal Care • Praveen Mummaneni MD, co-director of the Neurospinal a 50% complication rate • NeuroPoint Alliance — for Elderly Patients: New Disorders Program, has for operations on these a multi-center, prospective High-Risk Spine Team recently begun a collaboration patients. Adjacent segment registry that collects data and Research Models with scientists Jacqueline degeneration and junctional on patients who receive kyphosis are common in • A high-risk spine team Bresnehan PhD and Michael lumbar surgery for lumbar Parkinson’s patients, and has been formed at Beattie PhD at the Brain disc degeneration, herniated these patients often require UCSF to improve surgical and Spinal Injury Center to discs, or spondylolisthesis. multiple surgeries to treat care for elderly patients develop models of spinal By following these patients spinal deformity. (> 65 years) with spinal cord injury in elderly patients. UCSF Neurosurgery – Deformity Cases

120

100 97 82 80

60 46 Cases 40 36 24 19 20 12 Surgical case volumes for 1 spinal deformity have been 0 steadily increasing at the 2003 2004 2005 2006 2007 2008 2009 2010 UCSF Spine Center Year

19 Upadhyaya CD, Starr PA, Mummaneni PV. Spinal deformity and Parkinson disease: a treatment algorithm (Review). Neurosurg Focus 2010;28(3):E5. Prestige Cervical Artifi cial Disc – Five-Year Results The fi ve-year results of the Prestige® cervical artifi cial disc trial were published in September 2010 in Journal of Neurosurgery Spine, and showed that the replacement was effective at maintaining motion at fi ve years. The study enrolled young patients needing one cervical disc decompression and reported the longest follow-up of any prospective, randomized cervical spine trial performed in the U.S. Burkus JK, Haid RW, Traynelis VC, Mummaneni PV. Long-term clinical and radiographic outcomes of cervical disc replacement with the Prestige disc: results from a prospective randomized controlled clinical trial. J Neurosurg Spine 2010;13(3):308-18. Minimally Invasive Spine Surgery for Scoliosis The minimally invasive spine surgery program at UCSF, which focuses on outpatient and short-stay spinal surgery, continues to expand. Our team recently published one of few reports of outcomes for minimally invasive spine surgery for scoliosis, suggesting that it is a promising method for reducing surgical morbidity. Wang MY, Mummaneni PV. Minimally invasive surgery for thoracolumbar spinal deformity: initial clinical experience with clinical and radiographic outcomes Neurosurg Focus 2010;28(3):E9. They have also developed of the literature. Neurosurgery be presented February 26 – a new minimally invasive 2010;67(2):435-45. March 4, 2011 at the 100th Annual Meeting of the United States and technique to remove spinal Scheer JK, Tang J, Eguizabal Canadian Academy of Pathology, J, et al. Optimal reconstruction tumors that involves small San Antonio, TX. openings, less blood loss, technique after C-2 and spondylectomy: a biomechanical Naujokas A, Modera P, Weinstein P, and less morbidity. analysis. J Neurosurg Spine Tihan T. Spinal Cord Ependymomas: Chou D, Lu DC. Mini-open 2010;12(5):517-24. UCSF Experience 1983-2010. To be presented February 26 – transpedicular corpectomies with • Review expandable cage reconstruction. March 4, 2011 at the 100th Annual J Neurosurg Spine. In press. In collaboration with UCSF Meeting of the United States and Canadian Academy of Pathology, neurospinal surgeons and San Antonio, TX. Spinal Tumors neuroradiologists, the • Analysis of Surgical • Surgical Techniques Division of Neuropathology has begun an intensive Technique Shows Improved The members of the review of a database of 352 Neurologic Recovery Neurospinal Disorders primary spinal cord and For patients with spinal cord Program are experts in nerve root tumors treated compression from tumors, the treatment of primary since 1983. Pathological and infection, or trauma, Dean and metastatic tumors anatomical characteristics Chou MD and colleagues occurring from the skull base of the tumors are being have shown that approaching to the sacrum. Over 150 correlated with clinical these pathologies from the spine tumor surgeries are outcome after surgery with back instead of through the performed at UCSF each respect to neurological chest or leads to year and our surgeons are defi cit, tumor recurrence, a better rate of neurological continually at the forefront of response to radiation recovery. The team believes developing new techniques therapy, and need for repeat this may be because the for optimal resection. operations. Preliminary decompression occurs in a Acosta FL Jr, Sanai N, Cloyd J, results in 134 ependymomas circumferential manner, as Deviren V, Chou D, Ames CP. and 178 nerve sheath tumors Treatment of Enneking Stage 3 opposed to just on one side. Aggressive Vertebral Hemangiomas have identifi ed pathological Although this represents With Intralesional Spondylectomy: characteristics that will more preliminary data, it appears 21 Report of 10 Cases and Review of accurately defi ne criteria for that this approach can the Literature [published online ahead classifi cation and prediction improve neurologic recovery. of print Sep 14 2010]. J Spinal Disord Tech. of results of surgery. Lu DC, Lau D, Lee JG, Chou D. The transpedicular approach compared Cloyd JM, Acosta FL Jr, Polley Naujokas A, Modera P, Weinstein P, with the anterior approach: an MY, Ames CP. En bloc resection Tihan T. Uncommon Patterns and Opposite page, top: analysis of 80 thoracolumbar for primary and metastatic tumors Clinical Features of Peripheral Nerve Phillip Weinstein MD corpectomies. J Neurosurg Spine of the spine: a systematic review Sheath Tumors of the Spinal Cord: UCSF Experience 1983-2010. To 2010;12(5):583-91. Opposite page, bottom: En bloc spondylectomy is the best treatment option for a variety of spinal tumors. This technique removes the tumor without violating its margins. Far left: Dean Chou MD Middle left: Minimally invasive transpedicular discectomy of the thoracic spine is performed through a tube just 26 mm in diameter. Near left: Christopher Ames MD Below: Praveen Mummaneni MD Pediatric Neurological Surgery Nalin Gupta MD, PhD Pediatric Neurological Surgery Kuris Auguste MD Faculty Mitchel Berger MD

Ronald Shallat MD

Peter Sun MD Pediatric Neuro- Oncology

Anuradha Banerjee MD

Sabine Mueller MD, PhD

Theodore Nicolaides MD

Michael Prados MD Pediatric Research Laboratories

Arturo Alvarez- Buylla PhD Developmental neuroscience; stem-cell neurobiology

John Fike PhD Neurogenesis and radiation Injury

22 Nalin Gupta MD, PhD Pediatric brain tumors; cell-cell interactions; drug delivery strategies Nalin Gupta MD, PhD, Chief of Pediatric Neurological Surgery, performs the fi rst surgery to implant Jeanette Hyer PhD human neural stem cells to treat Pelizaeus-Merzbacher disease. Primitive neruoectodermal tumors

C. David James PhD Clinical Trials trial of neural stem cell • Management of Molecular biology of transplantation for Pelizaeus- Myelomeningocele The Pediatric Neurological CNS cancer; analysis Merzbacher disease (PMD), Study (MOMS): The program at UCSF of mutant epidermal a rare condition that prevents Treatment Center at UCSF is involved in a number of growth factor receptors the formation of myelin in has nearly completed innovative clinical trials to in malignant gliomas; male children. The study is enrollment for the fi rst evaluate promising therapies rodent model testing of sponsored by StemCells, clinical trial of fetal surgery for pediatric neurosurgical experimental therapies Inc. and is one of few for myelomeningocele − a disorders that are diffi cult to human clinical trials testing condition that may cause treat with standard regimens. David Rowitch MD, PhD the therapeutic potential of paralysis, deformity, or Central nervous system • PMD Clinical Trial: Chief neural stem cells. As a Phase and is usually development and of I study, the primary goal is discovered during the tumorigenesis Nalin Gupta MD, PhD to ensure the safety of the second trimester. MOMS is a and Chief of therapy, but investigators will randomized surgical trial that David Rowitch MD, PhD also be using MRI scans to is comparing the outcomes are principal investigators search for evidence of new of infants treated in utero of a new Phase I clinical myelin formation. to those treated after birth. Pediatric Neurological Surgery

Investigators for the trial, Disease Program at UCSF William A. Weiss MD, including Chief of Pediatric Benioff Children’s Hospital. PhD is the principal Neurosurgery Nalin Gupta He is an active participant investigator of the PBTF MD, PhD, will be analyzing in clinical trials consortia Institute project studying the results of this landmark for pediatric brain tumors the role of the oncogene study in the months to come. and was recently awarded MYCN in the formation the Pediatric Cancer Career of medulloblastoma. He • Pediatric Brain Tumor Development Award from and his collaborators Clinical Trials: The Pediatric the American Association of have demonstrated that Brain Tumor Center at UCSF to study targeted expression of participates in Phase I and II irreversible EGFR inhibitors in MYCN in a rodent model trials of promising therapeutic pediatric malignant glioma. contributes to initiation, drugs, new biological Top: Fetal MR image progression, and therapies, treatment delivery Sabine Mueller MD, PhD is showing a myelomeningocele of medulloblastoma, further sac (arrow) protruding from technologies, and radiation a board-certifi ed pediatric establishing it as a viable the posterior spine treatment strategies for all neurologist with special target for new pediatric brain Middle: Theodore Nicolaides MD types of newly diagnosed fellowship training in pediatric tumor therapies. and recurrent CNS tumors. neuro-oncology in the Bottom: Sabine Mueller Ongoing trials are performed Departments of Swartling FJ, Grimmer MR, Hackett MD, PhD through the Pediatric Brain and at UCSF. Dr. CS, et al. Pleiotropic role for MYCN in medulloblastoma. Genes Dev Tumor Consortium and Mueller treats children with 2010;24(10):1059-72. the Children’s Oncology brain tumors and associated Group, as well as through genetic syndromes, such Clinically relevant animal several industry partnerships as neurofi bromatosis 1 and models of disease are critical evaluating investigational tuberous sclerosis. Her basic for translating therapies agents sponsored by leading science research focus is from bench to bedside. The biotechnology companies. to establish pediatric brain Department of Neurological 23 Surgery’s Animal Model Mishra KK, Squire S, Lamborn K, tumor models for in vivo drug Core, led by C. David James Banerjee A, Gupta N, Wara WM, testing, while her clinical Prados MD, Berger MS, Haas-Kogan research interests lie in PhD, uses transplantable DA. Phase II TPDCV protocol for studying the late effects of xenograft, allograft, and pediatric low-grade hypothalamic/ treatment on children with isograft tumor models in chiasmatic gliomas: 15-year update. support of pediatric brain J Neurooncol 2010;100(1):121-7. brain tumors. tumor translational research. Nicolaides T, Tihan T, Horn B, Biegel J, Prados M, Banerjee A. High-dose Pediatric Brain Tumor Hashizume R, Ozawa T, Dinca EB, chemotherapy and autologous stem Foundation Institute Banerjee A, Prados MD, James CD, cell rescue for atypical teratoid/ at UCSF Gupta N. A human brainstem rhabdoid tumor of the central glioma xenograft model enabled nervous system. J Neurooncol The research program of for bioluminescence imaging. J Neurooncol 2010;96(2):151-9. 2010;98(1):117-23. the PBTF Institute at UCSF focuses on medulloblastoma Hashizume R, Gupta N, Berger New Pediatric Neuro- and brainstem glioma – MS, Banerjee A, Prados MD, Oncology Faculty Ayers-Ringler J, James CD, alternately the most common VandenBerg SR. Morphologic and Join UCSF Benioff and least treatable types molecular characterization of ATRT Children’s Hospital of pediatric brain tumors. xenografts adapted for orthotopic PBTF investigators are therapeutic testing. Neuro Oncol Theodore Nicolaides MD is 2010;12(4):366-76. a board-certifi ed pediatric also involved in developing oncologist who treats reliable animal models children with brain tumors of various pediatric brain in the Cancer and Blood tumors to test new therapies prior to clinical trials. Pediatric Epilepsy Center

The pediatric epilepsy Pediatric cranial epilepsy surgery program, directed surgery now routinely by Kurtis Auguste MD, has employs technology continued its growth and that merges the typical expansion over the past year, array of preoperative and surgical case volumes images (MRI, DTI, MEG, have seen a 20% increase. PET) onto intraoperative The practice regularly neuronavigation systems cares for the most complex for optimal seizure focus pediatric epilepsy patients. localization. The vast majority Treatment modalities of surgical patients have range from Gamma Knife become free of seizures or therapy and vagal nerve have experienced a dramatic stimulators to implantation improvement in their of indwelling subdural grids seizure profi les without and hemispherectomies. signifi cant complications.

UCSF Nerve Injury Clinic

The UCSF Nerve Injury Clinic adult neurological surgery, including non-invasive is one of the largest, multi- neurology, and orthopedic and surgical management. disciplinary practices for surgery collaborate to Surgery may include nerve the diagnosis and treatment care for patients, and form exploration and repair using of complex injuries of the diagnoses in conjunction intraoperative nerve studies peripheral nervous system. with neuroradiologists and nerve grafting. 24 The Clinic also cares for using neurography and patients with nerve tumors other investigations. and entrapment syndromes. Comprehensive treatment Specialists in pediatric and plans are provided,

UCSF Neurological Surgery Program

The Department of neuropathic and Neurological Surgery at non-neuropathic facial UCSF is home to top pain, including: specialists in the treatment of • Microvascular severe facial pain syndromes, Decompression Framless stereotactic MR image including trigeminal • Gamma Knife Radiosurgery with superimposed position of motor neuralgia. cortex stimulation electrodes. Motor We offer the most advanced • Radiofrequency cortex stimulation is the only surgical treatment option for patients with surgical treatment options for • Motor cortex Stimulation neuropathic facial pain that does not respond to . Center for Neural Engineering & Prostheses University of California • Berkeley / San Francisco

Center for Neural Engineering and Prostheses Launched in December 2010, the Center for Neural Engineering and Prostheses (CNEP) at UC Berkeley and San Francisco integrates cutting-edge engineering with world-class basic and clinical to develop technology to restore sensory, motor, and cognitive function in patients from disabling neurological conditions.

Our mission is to create algorithms for estimation and trials to quickly move new a multi-disciplinary control; 3) exoskeletons discoveries to real-world environment for 1) training and prosthetic devices. clinical applications. future neural engineers In neuroscience, our goals and clinicians; 2) scientifi c Education are to develop new animal research and neural models and computational At CNEP, we are training prosthetic technology methodologies to understand the next generation of development; and 3) effi cient the basic neural signals technology innovators and translation of research into underlying sensorimotor care providers to develop human clinical trials. 25 and cognitive function and devices that will interface with Faculty the central nervous system. Research and learning. We will apply this new knowledge to develop A new track in the UCSF-UC Clinical Translation Berkeley Joint Bioengineering Edward Chang MD, biomimetic and intuitive Graduate Program will co-director, UCSF The research goals of the technologies for preclinical CNEP are to combine models. We will use be developed, featuring Jose Carmena PhD, expertise in engineering and functional neuroimaging to integrated curriculum and co-director, UC Berkeley neuroscience to develop discover new brain targets coursework in: novel technology and to and circuits in humans for • engineering (signal further defi ne basic principles intervention and modulation. processing, neural interfaces, of . The clinical goal of the CNEP bioMEMS, integrated circuits, In engineering, our goals are is to implement a bench- control systems) to apply expertise in material to-bedside approach to • neurosciences , integrated circuits, effi ciently translate basic (neurobiology, neural signal, machine learning, control research and technology computational neuroscience) theory, and towards into clinical practice. Our three core project areas: faculty have considerable • clinical medicine 1) bidirectional, wireless, experience with surgical (neurobiology of disease, fully implantable neural implantation, ethics and hospital rotations in the interface systems; 2) regulation, and clinical clinic and operating room, bioethics) UCSF Department of Neurological Surgery Nonprofit Org. 505 Parnassus Avenue, 779 M U.S. Postage San Francisco, CA 94143-0112 PAID University of California San Francisco

Department of Neurological Surgery University of California, San Francisco 505 Parnassus Ave., Room 779 M San Francisco, CA 94143-0112 Phone: (415) 353-7500 Fax: (415) 353-2889 neurosurgery.ucsf.edu