the department of 1 neurological surgery at ucsf

2012 year in review

University of California San Francisco

Neurological Surgery letter from the chair

Dear Colleagues: quality and cost analysis studies (page 23). A recent analysis done in conjunction In these pages you will find some of this with their colleagues in the Department year’s major accomplishments from the of Orthopaedic Surgery revealed that Department of Neurological Surgery at for surgeries planned to be performed UCSF. A new national clinical trial for a over two or more stages, the later stages brain tumor vaccine developed by Dr. are categorized as readmissions under Andrew Parsa (page 4). A new program the “all-cause readmissions” metric to streamline multidisciplinary care for used by Medicare. With the launch of patients with sports concussions and brain Medicare’s new program to penalize injuries (page 8). A new laser treatment medical institutions based on readmission protocol for medically refractory epilepsy rates, this will be an important issue for (page 12). But I would particularly like to government to address. note the outstanding progress made by contents our Quality and Safety Program, led by Dr. Patient satisfaction is also a critical Brain Tumor Center 3 Catherine Lau (page 26). The efforts of this part of evaluating care, and I would program resulted in a 2012 Healthgrades like to congratulate our adult neuro- Brain & Spinal Injury Center 8 Neurosurgery Excellence Award, oncology team for winning the UCSF Vascular Neurosurgery 10 recognizing the best in patient safety. Medical Center’s Pinnacle Award for an unprecedented fifth year in a row. The I am also honored to be serving as the Epilepsy 12 Pinnacle Award recognizes the outpatient 81st president of the American Association service with the highest patient satisfaction Movement Disorders 15 of Neurological Surgeons (AANS), which scores. The neuro-oncology team has has provided me with a platform to Pediatric also been joined by a remarkable group of address quality and safety in neurosurgery Neurosurgery 17 philanthropists, led by Randi Murray, Cathy at a national level. Podell, and Marritje Greene, in creating Center for Management & This year, the NeuroPoint Alliance a new program aimed at supporting Surgery of Peripheral – established by the AANS in 2008 – caregivers (page 3). The importance of Nerve Disorders 20 began the pilot program for the National providing support for caregivers of patients Surgical Neurosurgery Quality and Outcomes with serious or terminal illness cannot be Pain Management Program 22 Database (N2Q0D). The purpose of this overemphasized. The Caregiver Program database is to track quality of surgical will provide one-on-one support from a Neurospinal Disorders 23 care for the most common neurosurgical social worker trained specifically to guide Neurosurgery Patient Safety procedures, as well as provide practice families suffering with the diagnosis of a & Quality Improvement Program 26 groups and hospitals with an infrastructure brain tumor. for prospective data collection and I am very proud of the work done this UCSF Neurological Surgery self-assessment. The Department of year to make the experience for patients Community Extension Program 28 Neurological Surgery at UCSF is one of 28 and their families the best it can be. groups participating in the pilot program. Center for Neural That mission will continue to drive Engineering & Prostheses at In addition to allowing us to compare everything we do in the Department UC Berkeley/San Francisco 29 the relative effectiveness of therapies of Neurological Surgery. and related quality-of-life measures, Department of the N2QOD will be critical for justifying Neurological Surgery payment for neurosurgical procedures in a new era of healthcare that will heavily University of California, weight quality and performance. For better San Francisco or worse, the medical community as a 505 Parnassus Ave., whole needs to begin gathering robust Room 779 M data that provide evidence for the value of Mitchel S. Berger, MD, FACS, FAANS San Francisco, CA our interventions to insurance companies 94143-0112 and lawmakers. We also need to ensure Kathleen M. Plant Distinguished Professor that we are involved in defining the and Chairman Phone: (415) 353-7500 benchmarks for success. Fax: (415) 353-2889 Department of In the Department of Neurological Surgery, Neurological Surgery neurosurgery.ucsf.edu our neurospinal disorders group has become especially involved in performing Director, UCSF Design & layout: Victoria Maier Magbilang, Brain Tumor Center Aqua Design Studio Illustration: Kenneth Xavier Probst Photography: Cindy Chew, Marco Sanchez, Frank Tapia, Anne Garrity, Ilona Garner Principal editor: Ilona Garner [email protected] brain tumor center

faculty 3 Adult Neuro-Oncology Nicholas Butowski MD Susan Chang MD Jennifer Clarke MD, MPH Michael Prados MD

Adult Brain Tumor Surgery Manish Aghi MD, PhD Mitchel Berger MD Brain Tumor Center supporters Randi Murray, Marritje Greene, Ira Glass, and Cathy Podell. Edward Chang MD “We are so grateful for the tireless efforts of this dedicated group Sandeep Kunwar MD of philanthropists. Without fundraising it is difficult to establish Michael McDermott MD programs specifically aimed at providing support to caregivers. Andrew Parsa MD, PhD

Their work will make the road easier for other families dealing Neuropsychology with the diagnosis of a brain tumor.” Caroline Racine PhD – Susan Chang, director of neuro-oncology California Center for Pituitary Disorders Brain Tumor Center at patients with brain tumors treated at UCSF. Family members are often overwhelmed Manish Aghi MD, PhD UCSF Establishes Program by the emotional toll and responsibility that Lewis Blevins, Jr. MD for Caregivers with Support comes with caring for a loved one with a from Dedicated Donors brain tumor. By providing them with the Sandeep Kunwar MD resources and support that they need, and Activists patients often have better outcomes. On April 21, 2012 Ira Glass, host and producer of National Public Radio’s “This Neuro-Oncology Service American Life,” talked to supporters of the Enters UCSF ‘Hall of Fame’ UCSF Brain Tumor Center about the loss of for Patient Satisfaction his brother-in-law Gordon Murray to brain cancer at a benefit that raised $1.2 million The Neuro-Oncology Service was given to establish a new program to help patient the UCSF Medical Center Pinnacle Award caregivers. “I know how lucky we were for an unprecedented fifth year in a row, that he was able to receive the outstanding making it the first service to be inducted care he did at UCSF,” said Mr. Glass. “It into the Pinnacle Award Hall of Fame. really is an extraordinary institution.” The Pinnacle Award recognizes the UCSF medical service with the best patient The fundraising efforts were led by Mr. satisfaction scores for outpatient care. Glass’ sister Randi Murray, Cathy and Mike Podell, and Marritje and Jamie Greene. The money raised will fund three years of operations costs that includes a dedicated social worker to assist the caregivers of The Division of Neuro-Oncology consistently receives top scores for patient satisfaction. faculty Research Laboratories brain tumor center Manish Aghi MD, PhD Oncolytic viral therapies; 4vascular biology of glioma Aruturo Alvarez-Buylla PhD Developmental neuroscience; National, Randomized effectiveness of bevacizumab or the stem cell biology Phase II Clinical Trial of vaccine alone. The trial will be conducted through the Alliance for Clinical Trials in Krystof Bankiewicz MD, PhD Heat-Shock Protein Oncology – a national cooperative group Drug delivery strategies; gene therapy Vaccine for Brain Tumors funded by the National Cancer Institute. Arnau Benet MD In a multicenter phase 2 clinical trial, a Initial funding for the trial was derived in Surgical anatomy; novel surgical brain cancer vaccine tailored to individual part from UCSF’s Specialized Program approaches patients by purifying heat shock proteins of Research Excellence (SPORE) for from their own tumors has proven effective brain tumors, which has been continually Mitchel Berger MD at extending their lives by several months awarded to the Brain Tumor Research Brain mapping; molecular and or longer. Center by the NCI since 2002. genetic basis of brain tumors The trial was initiated by principal During the most recent funding cycle of Gabriele Bergers PhD investigator Andrew Parsa MD, PhD, the SPORE grant, Dr. Parsa and BTRC Angiogenesis; tumor invasion who worked to develop the personalized principal investigator Russell Pieper PhD Soonmee Cha MD vaccines with biotechnology company examined the role of the brain tumor Neuroimaging Agenus, Inc. The results were presented microenvironment in modulating tumor this year in a plenary session at the annual vaccine efficacy. Their work has shown Joseph Costello PhD meeting of the American Association of that the tumor is not only influenced Functional genomics Neurological Surgeons. by the microenvironment, but actively Nalin Gupta MD, PhD manipulates it to support its own survival. The trial found that the vaccine, given to Pediatric brain tumors; more than 40 patients, extended survival Drs. Pieper and Parsa discovered cell-cell interactions by several months when compared that the immunosuppressive surface Daphne Haas-Kogan MD to 80 other patients who were treated protein B7-H1, which is overexpressed Cell signaling; genetic mutations; at the same hospitals and received in most glioblastoma cells, mediates therapeutic irradiation enhancement standard therapy—47 weeks compared the elimination of immune cells when to 32 weeks. Several of the patients who they come into contact with the tumor. C. David James PhD received the vaccine have survived for They have also gathered evidence Molecular biology of CNS cancers; more than a year. that an immune response is further rodent model testing of hampered by tumor-specific activation These promising results have provided experimental therapeutics of phosphatidylinositol 3-kinase (PI3K). the rationale for a three-arm, randomized A future trial combining the heat shock Andrew Parsa MD, PhD clinical trial to determine effectiveness protein vaccine with a PI3K inhibitor in Immunotherapy of the vaccine combined with the drug patients with B7-H1-suppressed tumors is bevacizumab (an anti-vascular therapy Claudia Petritsch PhD a goal of the next phase of the UCSF Brain now considered to be standard of care Brain cancer stem cells; Tumor SPORE. asymmetric stem cell division; for recurrent glioma) compared to the novel tumor suppressor genes Joanna Phillips MD, PhD Neuropathology; interaction between tumor cells and the microenvironment Russell Pieper PhD Signal transduction; models of human gliomagenesis and drug resistance G-200+ bevacizumab David Rowitch MD, PhD Central nervous system development; tumorigenesis William Weiss MD, PhD G-200 alone followed 18 Months Follow up Mouse models of human brain tumors; Recurrent >90% by bevacizumab at cell signaling GBM Resection; progression KPS>70 Survival Randomize John Wiencke PhD Path Confirmed GBM

Biomarker development and > 6 vials Manufacture application in brain tumor etiology Bevacizumab alone Margaret Wrensch MPH, PhD Genetic and molecular epidemiology of adult glioma

Shichun Zheng PhD A new randomized, three-arm trial of a heat-shock Molecular neuroepidemiology protein vaccine combined with bevacizumab will be offered through the Alliance for Clinical Trials in Oncology gradient at the tip of the cannula pushes interstitial fluid out of the way, enabling coverage of larger brain volumes than could be achieved by diffusion alone. In 2012, the trial’s principal investigator Manish Aghi MD, PhD has successfully used ClearPoint to monitor infusion in two patients and will be following them in the coming months to assess safety, tolerability, and preliminary efficacy. This trial has been developed by Tocagen Inc., and study sites include UCSF, UCLA, UCSD, and Cleveland Clinic.

c-MET Inhibitors Offer The ClearPoint MRI-compatible clinical system for convection enhanced delivery of nanoparticles to brain tumors was Potential for Augmenting Anti- developed through a collaboration between the medical device company SurgiVision and UCSF faculty Philip Starr MD, PhD, Paul Larson MD, and Alistair Martin PhD. VEGF Therapy in Brain Tumors The laboratory of principal investigator Gabriele Bergers PhD has recently focused Parsa AT, Crane C, Han S, Kivett V, Fedoroff Patients take the non-toxic oral drug on events that drive migration of tumor A, Butowski N, Chang S, Prados M, Clarke 5-fluorocytosine (5-FC) and then a cells in patients being treated with vascular J, Berger M, McDermott M, Aghi M, Sloan retrovirus carrying the enzyme cytosine endothelial growth factor (VEGF) inhibitors, A, Bruce J. A phase 2 multicenter trial of deaminase (CD) is injected directly into the such as bevacizumab. autologous heat shock protein peptide tumor. The retrovirus spreads throughout vaccine (HSPPC-96) for recurrent glioblastoma the tumor by replicating itself in dividing VEGF inhibitors target the increase in multiforme (GBM) patients shows improved tumor cells, while the CD it carries converts angiogenesis that occurs in highly vascular survival compared to a contemporary the 5-FC that has accumulated in the tumor tumors, such as glioblastoma. While most cohort controlled for age, KPS and extent of cells into cytotoxic 5-fluorouracil (5-FU). patients experience beneficial effects of resection. Presented at: American Association treatment, those effects are largely and of Neurological Surgeons Annual Scientific A key component of success for this transient and tumors invariably recur. In Meeting; April 17, 2012; Miami, FL. new therapy will be to ensure that a subset of patients, VEGF blockade is the initial infusion of the retrovirus is associated with recurrent tumors that have a spreading throughout the target region. Clinical Trial Testing more diffuse and infiltrative growth pattern, Neurosurgeons are now able to monitor which makes them difficult to resect. Convection Enhanced Delivery the infusion of the retrovirus in real time of Toca 511 is Enhanced by using the ClearPoint system, which was The Bergers lab has now identified the developed at UCSF and uses an MR- molecular mechanisms by which VEGF Real-Time Imaging compatible skull mounted device for ablation causes enhanced invasion, The UCSF Brain Tumor Research Center is performing implantation of deep brain demonstrating that VEGF directly and offering a phase 1 clinical trial of Toca 511 stimulator electrodes or drug infusion negatively regulates tumor cell invasion – a new treatment regimen for recurrent cannulae in the MR scanner. through formation of a novel cMet:VEGFR2 receptor complex, which suppresses glioblastoma that combines attributes of Using convection enhanced delivery – gene therapy and chemotherapy. HGF-dependent c-Met phosphorylation developed and refined in the laboratory of and tumor cell migration. Consequently, Krystof Bankiewicz MD, PhD – a pressure

The yin and yang of vascular endothelial growth factor (VEGF) signaling. Murine glioblastomas that overexpress VEGF are highly proliferative and angiogenic, but have well-defined, circumscribed borders (left side). At the opposite extreme, murine glioblastomas deficient in VEGF are nonangiogenic, slower growing, but highly invasive (right side). Tumor cells are red, blood vessels are green, and nuclei are blue. 6

VEGF blockade restores or increases of patients with low-grade gliomas have Genome Sequencing Zeroes c-Met activity in GBM cells in a hypoxia- such mutations and that their presence is independent manner while inducing an associated with longer survival. in on Risk for Developing EMT-like program. Oligodendroglioma and The IDH1 mutations have been shown to These findings support combined cause an increase in production of the IDH1/2-Mutated Astrocytoma treatment strategies targeting both VEGF oncometabolite 2-hydroxyglutarate (2HG), Groundbreaking new research from the and c-Met in glioblastoma patients in order which the research team was able to UCSF Brain Tumor Research Center and to overcome pro-invasive resistance and measure in the tissue samples using the the Mayo Clinic has shown that certain prolong survival. nuclear magnetic resonance technique subtypes of gliomas are connected to of proton high-resolution magic angle Lu KV, Chang JP, Parachoniak CA, Pandika specific inherited variation in a small, non- spinning spectroscopy. 2HG is present MM, Aghi MK, Meyronet D, Isachenko N, coding region of the genome. in extremely small quantities and UCSF Fouse SD, Phillips JJ, Cheresh DA, Park M, is one of the only institutions with the Building on their previous work Bergers G. VEGF inhibits tumor cell invasion technology sensitive enough to measure it. demonstrating that single nucleotide and mesenchymal transition through a MET/ polymorphisms (SNPs) at 8q24 VEGFR2 complex. Cancer Cell 2012; There was an 86.4% concordance near CCDC26 are inherited risk loci for 22(1):21-35. between the detection of 2HG in the oligodendroglial tumors and astrocytomas spectra with the presence of the IDH1 with mutated IDH1 or IDH2, the research Magnetic Resonance mutation. The 2HG was correlated with team has now shown that the low- Spectroscopy Detects cellular density and other vivo parameters frequency SNP rs55705857 within 8q24.21 that may be useful in designing new is the SNP most strongly associated with Oncometabolite Associated methods for evaluating non-invasively in tumor formation. With Improved Survival in Low- patients whether recurrent tumors have The variant in rs55705857 substitutes Grade Tumors remained grade II or undergone malignant transformation to a higher grade. guanine for adenosine and is about 6 times A team of UCSF neuroimaging more common in people who have these Further work is underway at UCSF to specialists led by Sarah Nelson PhD has types of tumors than people who do not. translate these findings to the in vivo used advanced magnetic resonance setting by using a clinical MR scanner. The findings, published this year inNature spectroscopy techniques to detect Noninvasive monitoring of 2HG in the clinic Genetics, suggest that the variant in a novel molecular marker that could may help physicians better predict patient rs55705857 either contributes to IDH1/2 be useful in predicting outcome and survival, gauge cancer recurrence, make mutation or interacts with IDH1/2 mutation evaluating new treatments for patients follow-up treatment decisions, and assess to facilitate development and progression of with low-grade glioma. response to therapy. glioma. Although the exact function of the Dr. Nelson and her colleagues gathered variant is unknown, it is located in a highly Elkhaled A, Jalbert LE, Phillips JJ, Yoshihara image-guided tissue samples from patients conserved region and may effect gene HAI, Parvataneni R, Srinivasan R, Bourne G, with recurrent gliomas that had been regulation as a non-coding or microRNA. Berger MS, Chang SM, Cha S, Nelson SJ. grade II at initial diagnosis and analyzed Magnetic resonance of 2-hydroxyglutarate in The study was jointly led by epi- them for the presence of mutations in the IDH-mutated low-grade gliomas. Sci Transl demiologists Margaret Wrensch PhD, IDH1 gene. Studies in the last two years Med 4(116):116ra5. and John Wiencke, PhD, professors in have shown that more than 70 percent brain tumor center 7

the Department of Neurological Surgery C, Rynearson AL, Fridley BL, Buckner JC, Surgical anatomist and principal at UCSF, and Robert Jenkins, MD, PhD, O’Neill BP, Giannini C, Lachance DH, Wiencke investigator Arnau Benet MD performs professor of Laboratory Medicine in the JK, Eckel-Passow JE, Wrensch MR. A surgical simulations in postmortem Department of Laboratory Medicine and low-frequency variant at 8q24.21 is strongly specimens and produces digital Pathology and the Division of Laboratory associated with risk of oligodendroglial tumors 3-D anatomic images for surgical Genetics at the Mayo Clinic. The col- and astrocytomas with IDH1 or IDH2 mutation. planning, development of novel surgical laboration between these investigators Nat Genet 2012;44(10):1122-5. approaches, and educational activities. resulted from interactions through the In collaboration with otolaryngologists NCI Specialized Program of Research New Surgical Anatomy Ivan El-Sayed MD and Larry Lustig MD Excellence (SPORE) for brain tumors, and Laboratory Explores Minimally and neurosurgeons Michael Lawton MD, the next phase of the UCSF SPORE will Mitchel Berger MD, Michael McDermott continue this comprehensive project on Invasive Approaches to MD, and Manish Aghi MD, PhD, Dr. integrative genomics of glioma survival. Brain, Skull Base, and Benet is exploring ways of optimizing Jenkins RB, Xiao Y, Sicotte H, Decker PA, Cerebrovascular Lesions surgical routes via endoscopic minimally Kollmeyer TM, Hansen HM, Kosel ML, Zheng A new laboratory at UCSF is focused invasive techniques to complex skull base S, Walsh KM, Rice T, Bracci P, McCoy LS, on developing more effective surgical regions. The laboratory is also working to Smirnov I, Patoka JS, Hsuang G, Wiemels strategies to treat complex cranial lesions develop minimally invasive transcranial JL, Tihan T, Pico AR, Prados MD, Chang with less impact to patients’ quality of life. microsurgical approaches to the skull base SM, Berger MS, Caron AA, Fink SR, Halder and subcortical structures using image- guided dissection.

Ivan El-Sayed MD, Arnau Benet MD, and Manish Aghi MD, PhD simulate a surgical procedure through the endonasal corridor. brain & spinal injury center 8 faculty Neurotrauma San Francisco General Hospital Geoffrey Manley MD, PhD Michael Huang MD Shirley Stiver MD, PhD Vincent Wang MD, PhD Diffusion tensor imaging of a mild traumatic brain injury. UCSF’s PlaySafe Program works with school districts across the Bay Area to treat and provide education about concussion and brain injury.

San Francisco General Hospital to provide The NIH and U.S. Department of Defense Transforming Research coordinated care for patients with sports now require the CDE to be used in all future concussions or other head injuries. and Clinical Knowledge clinical trials for traumatic brain injury. The in Traumatic Brain Injury II TRACK-TBI repository is also serving as The program includes a monthly clinic (TRACK-TBI II) the initial test dataset for the launch of the where patients are seen by experts from Federal Interagency Traumatic Brain Injury many fields, including sports medicine, Scientists at the UCSF Brain and Spinal Research (FITBIR) informatics system. physical medicine and rehabilitation, Injury Center, led by Geoffrey Manley MD, When fully implemented, FITBIR will provide neuropsychology, neuroradiology, PhD, are implementing the second phase access to high quality, curated data on a neurology and neurosurgery. of their prospective, longitudinal study bioinformatics platform that will accelerate Highlights of the Bay Area Concussion of traumatic brain injury patients, called the ability of researchers to collaborate and and Brain Injury Program: TRACK-TBI II. compare results across studies. • We use a team approach to treat each Their previous trial – TRACK-TBI – tested The emphasis on data sharing and patient, involving experts from a wide and refined the Common Data Elements development of common research range of specialties (CDE) for Traumatic Brain Injury, which tools across institutions and disciplines were developed with neuroscientists echoes a recent report by the National • Patients can be seen by all the from the NIH and U.S. Department of Academy of Sciences calling for large- specialists they need at a single Defense to provide new standards for scale data networks to be developed for clinic visit reporting and defining brain injuries across all diseases. The report, “Toward Precision studies. There are currently no validated Medicine: Building a Knowledge Network • Through UCSF’s PlaySafe Program, outcome measures to inform patients for Biomedical Research and a New we work with school districts across about their prognoses or any classification Taxonomy of Disease,” outlines a vision in the San Francisco Bay Area to treat schemes that take into account the which the most current research findings and raise awareness about concussion pathophysiological mechanisms that lead and patient data for a given disease are and brain injury. Athletes at participating to neurological deficit. entered into a central, interactive data schools receive: repository that can be accessed by – Comprehensive evaluation by a Collaborating with the University of clinicians and scientists. It would allow sports medicine physician trained Pittsburgh Medical Center, the University research to be more tightly integrated into in management of concussion Medical Center Breckenridge, and Mount clinical care and speed the implementation Sinai Rehabilitation Center, investigators of personalized treatment strategies. – Detailed step-by-step return to at UCSF established data repositories play progression program for clinical informatics, biospecimens, neuroimaging, and neurocognitive Comprehensive Care for – Consultation and communication outcome assessments. Sports Concussions and with the school’s certified athletic trainer or official In TRACK-TBI II, the data collection will Head Injuries be extended to 10 sites across the United The Bay Area Concussion and Brain States with the goal of providing clinicians Injury Program at UCSF is a new and researchers with current information multidisciplinary collaboration among that links genomic data, imaging clinicians from UCSF Medical Center, characteristics, neurocognitive outcomes, UCSF Benioff Children’s Hospital, and quality-of-life measures, and patient- specific demographic information. 9

BASIC Laboratories Michael Beattie PhD John Fike PhD Linda Noble-Haeusslein PhD central nervous system repair neurogenesis and traumatic brain injury neuroinflammation in traumatic brain and spinal cord injury Jacqueline Bresnahan PhD Jialing Liu PhD central nervous system repair neurogenesis and functional recovery S. Scott Panter PhD cellular injury following stroke and Adam Ferguson PhD Geoffrey Manley MD, PhD hemoglobin-based neurological injury bioinformatics basic, translational, and clinical traumatic brain injury research Susanna Rosi PhD chronic neuroinflammation; learning and memory

Spinal Cord Injury May Be Dr. Steven Rosen is a professor of The developing brain does not adequately anatomy at UCSF and Dr. Lee is a express many of the neuroprotective Tempered by Available postdoctoral fellow in the BASIC molecules of the adult brain, such as Anti-inflammatory Drug laboratories of Michael Beattie PhD antioxidants, and may be especially and Jacqueline Bresnahan PhD. vulnerable to extended exposure to With a grant awarded this year from neutrophils. While it has been shown that the U.S. Department of Defense, Linda the expression of neutrophil elastase in Noble-Haeusslein PhD will study an Understanding Traumatic Brain the injured brain worsens outcome, Drs. approved nonsteroidal anti-inflammatory Injury in the Developing Brain Semple and Noble-Haeusslein will for the drug (NSAID), which also functions as a first time examine its impact on social and sheddase for the molecule L-selectin, in One of the main challenges in treating cognitive functions in a mouse model. the treatment of spinal cord injury (SCI). children who suffer brain injuries is that they often develop social as well as Over the past 10 years Dr. Noble- cognitive problems. In a new five-year Haeusslein and her colleagues Steven Top: Neutrophils are present in the injured developing study funded by the National Institute brain, demonstrated here by immunolocalization of Rosen PhD and Sang Mi Lee PhD have for Neurological Disorders, postdoctoral myeloperoxidase (red), which is located in granules in been studying the role of the leukocyte fellow Bridget Semple PhD and principal these leukocytes. Bottom: A detailed view of the granules commonly found in the cytoplasm of neutrophils. adhesion molecule L-selectin in the investigator Linda Noble-Haeusslein PhD inflammatory process following SCI. They will study how neutrophil elastase may not have shown that knocking out L-selectin only cause local tissue damage following in mice substantially improves locomotor injury, but also impair normal development recovery after sustaining an SCI, making it of the brain. a promising therapeutic target. Unlike adults, children experience a The team has now identified a candidate prolonged trafficking of neutrophils into sheddase of L-selectin, which temporarily the brain following injury. Neutrophils “sheds” the molecule from the surface release proteases, such as neurtrophil of the leukocyte, to be further studied elastase, that can damage tissue. In adult as a potential therapy. The sheddase is mouse models of brain injury, neutrophils an existing FDA-approved NSAID that clear the brain within 24-48 hours of the would be repurposed for treating SCI. The insult. In the pediatric models, neutrophils new research will focus on defining the linger for up to two weeks. optimal dosing and therapeutic window for administering the drug. vascular neurosurgery 10

Neurosurgeons from UCSF provide treatment and training in Guadalajara, Mexico.

Project Altruista: Advancing of the pituitary tumor center at Johns malformation; temporal horn arteriovenous Hopkins and former neurosurgery resident malformation; acoustic neuroma; Neurosurgery in Mexico at UCSF, the team collaborated on the craniopharyngioma; and medulloblastoma. cases with Mexican neurosurgeons and In July 2012, a team of neurosurgeons and To get involved or find out more about residents to provide training on advanced volunteers from UCSF and Johns Hopkins Project Altruista, contact Dr. Lawton at: neurosurgical techniques. traveled to Guadalajara, Mexico as part [email protected] of Project Altruista to perform six pro- With donated equipment and limited bono surgeries at a civil hospital servicing resources, they successfully performed underprivileged patients. a wide range of complex procedures, Led by Michael Lawton MD, chief of including hemispherectomy for epilepsy vascular neurosurgery at UCSF, and and resections for deep cavernous Alfredo Quiñones-Hinojosa MD, director

Michael Lawton MD engages with Mexican residents and neurosurgeons during the second year of Project Altruista. “Our mission is small and fledgling, but unique: working with the local neurosurgeons, providing for the needy, and focusing on the complex cases with the greatest teaching impact.” — Michael Lawton MD, chief of vascular neurosurgery at UCSF

faculty

Vascular Neurosurgery Cerebrovascular Research Laboratories Michael Lawton MD Arnau Benet MD S. Scott Panter PhD surgical anatomy; novel surgical animal models of stroke and Michael Huang MD approaches traumatic brain injury Michael McDermott MD Michael Lawton MD William L. Young MD (Gamma Knife radiosurgery) pathophysiology of arteriovenous pathophysiology of arteriovenous malformation; hemodynamics of malformation; hemodynamics of aneurysms; radiation-induced arteriopathy aneurysms; predictors of brain hemorrhage in patients with Jialing Liu PhD arteriovenous malformations neurogenesis and functional recovery after stroke Time to Subsequent ICH (years) EOOH Yes EOOH No 11 Hemorrhage Free Probability Hemorrhage Free 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0

0 5 10 15 20 25

Number at Risk Entering Each 5 Year Interval EOOH Yes 41 10 8 7 4 1 EOOH No 658 68 44 31 20 15

Survival analysis of new intracranial hemorrhage (ICH) after diagnosis by evidence of old hemorrhage (EOOH). Copyright © 2012, Wolters Kluwer Health

Silent Microhemorrhaging of In a new study by the UCSF Center for These findings pave the way for develop- Cerebrovascular Research, investigators ing new risk-stratification schemes for Asymptomatic Arteriovenous found that ‘silent’ microhemorrhages patients with asymptomatic AVMs and Malformations Increases Risk — asymptomatic bleeding in the lesion the UCSF Vascular Neurosurgery Service of Intracranial Hemorrhage — are associated with a higher rate of is beginning to implement iron-sensitive subsequent ICH. The research team first MRI sequences that can detect the Approximately half of all brain became interested in this possibility when presence of microhemorrhages in patients. arteriovenous malformations (AVM) they observed microbleeding in their new Guo Y, Saunders T, Su H, Kim H, Akkoc D, are asymptomatic when detected. In animal model of AVM. Analyzing human Saloner DA, Hetts SW, Hess C, Lawton MT, managing these AVMs, physicians weigh surgical tissue collected through the UCSF Bollen AW, Pourmohamad T, McCulloch the risks of treatment against the risk of Brain AVM Study Project confirmed that CE, Tirhan T, Young WL. Silent intralesional intracranial hemorrhage (ICH). But there patients with symptomatic ICH also had microhemorrhage as a risk factor for brain have been few reliable predictors of how evidence of older bleeds, likely from silent arteriovenous malformation rupture. likely an asymptomatic AVM is to rupture. hemorrhaging of an asymptomatic lesion. Stroke 2012;43(5):1240-46.

Technical Refinements in Vascular Neurosurgery: Innovations from UCSF in 2012

Flash Fluorescence for a select patient group that may benefit lesions located near language and motor Middle Cerebral Artery Aneurysms from contralateral MCA clipping. While areas in the cingulate gyrus and deep this is often a controversial approach white matter of the medial frontal lobe. Distal middle cerebral artery (MCA) to these aneurysms, the more standard Neurosurgical resident Jason Davies MD, aneurysms often require bypass to treat, approach requires two craniotomies, Rabih Tawk MD, and Michael Lawton MD but their location can make efferent which some – especially elderly – recently detailed their experience with arteries, needed to redirect blood flow, patients cannot tolerate. The authors the technique in 11 patients in the difficult to identify. The flash fluorescence define the ideal aneurysms for this journal Neurosurgery. technique uses intraoperative procedure as unruptured, having simple Davies J, Tawk RG, Lawton MT. The videoangiography and indocyanine green necks, projecting inferiorly or anteriorly, contralateral transcingulate approach: dye to make the efferent arteries fluoresce associated with short M1 segments, and operative technique and results with vascular during surgery. This allows fast and reliable residing in older patients with sylvian lesions. Neurosurgery 2012; 71(1 Suppl identification of an appropriate recipient fissures widened by brain atrophy. artery for bypass. Operative):4-13. Rodríguez-Hernández A, Gabarrós A, Lawton Rodríguez-Hernández A, Lawton MT. MT. Contralateral clipping of middle cerebral Flash fluorescence with indocyanine green artery aneurysms: rationale, indications, and videoangiography to identify the recipient artery surgical technique. Neurosurgery 2012; 71(1 for bypass with distal middle cerebral artery Suppl Operative):116-23. aneurysms: operative technique. Neurosurgery 2012;70(2 Suppl Operative):209-20. Contralateral Transcingulate Approach to Cavernous Malformations and Contralateral Clipping of Arteriovenous Malformations Middle Cerebal Artery Aneurysms The contralateral transcingulate approach A recent article published by Michael may be a less invasive and safer route than Lawton MD and cerebrovascular fellow the contralateral transcallosal approach for Ana Rodríguez-Hernández MD defines epilepsy 12 faculty

Epilepsy Surgery Edward Chang MD Paul Larson MD

Epilepsy Research Laboratories Arturo Alvarez-Buylla PhD Scott Baraban PhD UCSF is now offering the Visualase™ thermal ablation system for surgical treatment of epilepsy.

New Minimally Invasive Laser procedure has not been widely adopted “As a medical community, — in fact, it is dramatically underutilized Surgery for Epilepsy Offered according to a study from epilepsy we are not practicing at UCSF: the Visualase™ specialists at UCSF. evidence-based medicine Thermal Ablation System The study, published in the April 2012 with regard to the The UCSF Epilepsy Center is excited issue of Neurology, showed that the to be offering a new minimally invasive number of Americans having the surgery treatment of patients system to surgically treat epilepsy. Using has not changed in the decade since who have epilepsy.” interventional MRI technology developed release of the effectiveness study, at UCSF, neurosurgeons guide an MR- though surgical treatment is now — Edward Chang, MD, chief compatible laser applicator into the brain uniformly encouraged by neurology and of adult epilepsy surgery toward the target lesion that is the source neurosurgery professional societies. of the patient’s seizures. The laser then The U.S. Centers for Disease Control heats and destroys the small, well-defined and Prevention estimates that 2 million area of abnormal tissue, leaving the Americans have epilepsy. Hundreds of surrounding tissue unharmed. Thermal thousands of these men, women and ablation is viewed in real-time on thermal children suffer from uncontrolled seizures, maps that display the distribution of heat but nationally only a few hundred are and successful target treatment. The entire treated surgically each year with UCSF procedure can be done through a single performing about 50 of the operations. burr hole. The state-of-the-art procedure has been adopted by select hospitals Among people who do have the operation, since 2010. the study found, there are significant disparities by race and insurance status. Patients eligible for thermal ablation must White patients were more likely to have have lesional epilepsy resulting from surgery than racial minorities, and privately tumors, hypothalamic hamartoma, or insured patients were more likely to medial temporal lobe sclerosis. undergo surgery than those with Medicaid or Medicare. Brain Surgery for “As a medical community, we are not Epilepsy Underutilized practicing evidence-based medicine with Ten years ago, a landmark clinical trial in regard to the treatment of patients who Canada demonstrated the unequivocal have epilepsy,” said Edward Chang, MD, effectiveness of brain surgeries for treating chief of adult epilepsy surgery in the UCSF uncontrolled epilepsy, but since then the Department of Neurological Surgery and Find out more about utilization of epilepsy surgery: 13 Englot DJ, Ouyang D, Garcia PA, Barbaro rates, and adverse perioperative events drug-resistant temporal lobe epilepsy: NM, Chang EF. Epilepsy surgery trends in at US epilepsy centers. J Neurosurg. a randomized trial. JAMA 2012;307(9): the United States, 1990-2008. Neurology 2012 Oct 26. [Epub ahead of print]. DOI: 922-30. 2012;78(16):1200-6. 10.3171/2012.9.JNS12776. Koubeissi M. Epilepsy surgery: a broken Englot DJ, Ouyang D, Wang DD, Rolston Engel J Jr, McDermott MP, Wiebe S, et bridge between utility and utilization. JD, Garcia PA, Chang EF. Relationship al.; Early Randomized Surgical Epilepsy Trial Epilepsy Curr 2012;12(5):194-6. between hospital surgical volume, lobectomy (ERSET) Study Group. Early surgical therapy for

the UCSF Epilepsy Center. “There are a lot right choice should be tailored to patient These findings suggest that improvements of people who are taking medications and preferences, age, and type of epilepsy in diagnostic imaging and surgical tools continuing to have seizures even though (focal, diffuse, or generalized). will continue to improve rates of seizure they can potentially be seizure-free.” freedom in this patient population. Rolston JD, Englot DJ, Wang DD, Shih T, A follow-up study showed that the Chang EF. Comparison of seizure control Rowland NC, Englot DJ, Cage TA, incidence of perioperative adverse events outcomes and the safety of vagus nerve, Sughrue ME, Barbaro NM, Chang EF. for epilepsy surgery was significantly thalamic deep brain, and responsive A meta-analysis of predictors of seizure higher at low-volume hospitals (12.9%) neurostimulation. Neurosurg Focus freedom in the surgical management than at high-volume centers (6.1%), 2012;32(3):E14. of focal cortical dysplasia. J Neurosurg indicating that patients with refractory 2012;116(5):1035-41. epilepsy should be referred to a high- Predicting Seizure Wang DD, Deans A, Barkovich AJ, Tihan T, volume, comprehensive epilepsy center Freedom after Surgery Garcia PA, Barbaro NM, Chang EF. Transmantle for surgical evaluation. for Epilepsy Caused by sign in cortical dysplasia: a unique radiologic entity with excellent prognosis for seizure- Comparing Electrical Cortical Malformations control. J Neurosurg, In Press. Stimulation Devices for Surgery can be an effective option to treat Epilepsy – How to medically refractory epilepsy caused by Study on Integration of focal cortical dysplasia, but results have Lab-Grown Interneurons Determine the Best been variable. A recent meta-analysis of Option for Each Patient published outcomes for resection reported Challenges Prevailing that 55.8% of patients achieve freedom A recent study at UCSF compared the Theory of Cell Fate from seizures after surgery. efficacy and side effect profiles of three Over the past two years, an exciting therapies that use electrical stimulation to Factors associated with higher rates of research program in the Department of mitigate seizures: deep brain stimulation seizure control included: partial seizures, a Neurological Surgery has been focused on (DBS), vagus nerve stimulation (VNS), and temporal location, detection with MRI, and generating interneurons from progenitor the Responsive Neurostimulator (RNS™). a Type II Palmini histological classification. cells, which can then be transplanted into Extent of resection was also an important Based on the results of randomized the brain to cure epilepsy. factor; complete resection of the epileptic trials, the three devices demonstrated foci correlated with greater seizure control. comparable seizure control, and the

A UCSF study compared vagus nerve stimulation (left), deep brain stimulation (middle), and the Responsive Neurostimulator for treating epilepsy (right). epilepsy

Hilar region of hippocampus in an epileptic mouse transplanted with GABA progenitor cells. MGE-derived interneurons are shown in green; parvalbumin-positive interneurons are shown in red.

Interneurons secrete the neurotransmitter in each transplant experiment varied by EUREKA! Prestigious GABA, which inhibits excitatory circuits in 200-fold, but the number of surviving the brain. The absence of GABA may lead transplants remained the same, expanding Grant for New Models to the uncontrolled electrical signaling in the cell population by no more than 35%. of Pediatric Epilepsy the brain that causes epileptic seizures. The investigators conclude that interneuron Scott Baraban PhD has been awarded cell fate is intrinsically determined, With funding from the National Institutes a EUREKA grant from the NIH for the independent of signaling from neurotrophic of Health and the California Institute for project “Using Zebrafish to Advance factors in the local environment. This Regenerative Medicine, the laboratories Our Understanding and Treatment of finding disputes the long-favored of Scott Baraban PhD and Arturo- Epilepsy.” Dr. Baraban and his team are neurotrophic hypothesis, which suggests Alvarez Buylla PhD have shown that using zebrafish mutants featuring a loss- that interneurons are overproduced in progenitors derived from the medial of-function sodium channel mutation to the embryonic ventral forebrain and then ganglionic eminence (MGE) region of adult identify molecular targets for therapeutic migrate to the cortex where the excess mouse brains can be transformed into treatment and screen drug candidates. The cells are eliminated through competition interneurons, produce GABA, and integrate epileptic zebrafish display a phenotype for neurotrophic factors. into the neocortex to block spontaneous similar to monogenic epilepsy disorders seizures. They are also investigating the Establishing the threshold for the number primarily seen in children, such as Dravet use of embryonic progenitors and whether of cells that can survive in the cortex syndrome and Severe Myoclonic Epilepsy or not seizures can be blocked in specific has important implications for planning of Infancy. genetic models of epilepsy. transplants of MGE progenitors in humans. According to the NIH, EUREKA The newest results from this research Southwell DG, Paredes MF, Galvao RP, Jones (Exceptional, Unconventional Research program, published this year in Nature, DL, Froemke RC, Sebe JY, Alfaro-Cervello Enabling Knowledge Acceleration) show that there is a threshold for the C, Tang Y, Garcia-Verdugo JM, Rubenstein grants fund “exceptionally innovative number of interneurons that can survive JL, Baraban SC, Alvarez-Buylla A. Intrinsically research projects that could have an and inhibit synaptic events after being determined cell death of developing cortical extraordinarily significant impact on many transplanted. The number of interneurons interneurons. Nature 2012;491(7422):109-13. areas of science.”

Scott Baraban PhD studies zebrafish models of epilepsy. Young wild-type (left) zebrafish are lighter than those with a sodium mutation that mimics Dravet syndrome (right). The zebrafish mutants are used in high-throughput drug discovery assays. movement disorders 15 Electrocorticography Reveals Novel Patterns of Cortical Synchronization in Patients with Movement Disorders The laboratory of Philip Starr MD, PhD has adapted the technique of electrocorticography, widely used in epilepsy, to study the pathophysiology of movement disorders.

The Starr lab uses electrocorticography to investigate the pathophysiology of movement disorders. Top row, left to In the past year, Dr. Starr and postdoctoral right: Nathan Rowland MD (neurosurgery resident), Philip Starr MD, PhD (PI). Bottom row, left to right: Nicki Swann PhD fellow Coralie deHemptinne showed (postdoctoral fellow), Coralie DeHemptinne PhD (postdoctoral fellow), and Elena Ryapolova BS (lab assistant). that in Parkinson’s disease, population spike activity in primary motor cortex is New Phase I Gene Therapy regions of the brain. It will also allow for excessively coupled to the phase of low monitoring of cannula flow – backflow frequency rhythms, and this pathological Trial for Parkinson’s Disease up along the cannula (and away from the oscillatory synchronization is ameliorated Using Real-Time Imaging of intended target) has been a technical issue by therapeutic deep brain stimulation. in many other trials of direct brain infusions Infusate The work was presented at the 2012 for a variety of neurosurgical disorders. UCSF will be performing the first gene Society for Neuroscience meeting. It reveals fundamental mechanisms by which therapy clinical trial for Parkinson’s What Therapy Will Be Administered? disease using real-time monitoring of a basal ganglia disease disrupts cortical viral vector infusion with the ClearPoint Patients will receive adeno-associated virus function, and gives novel insight into system. Developed at UCSF, ClearPoint is encoding human amino acid decarboxylase mechanisms of deep brain stimulation. (AAV2-AADC). AADC converts oral an MR-compatible skull-mounted aiming Crowell AL, Ryapolova-Webb ES, Ostrem levodopa to dopamine. If successful, the device with MR coils designed for optimal JL, Galifianakis NB, Shimamoto S, Lim DA, therapy will decrease dependence on imaging during surgery. Starr PA. Oscillations in sensorimotor cortex in medication and improve symptoms. movement disorders: an electrocorticography Why real-time imaging? study. Brain 2012;135(Pt 2):615-30. When Will the Trial Begin and Previous trials using gene therapy with How Can My Patients Enroll? DeHemptinne C, Ostrem JL, Garcia P, Chang direct infusion have been hampered E, Ryapolova-Webb E, Galifianakis NB, Starr by technical limitations. In one study, The trial will begin in the Spring of 2013. PA. Deep brain stimulation alters aberrant cross postmortem tissue from patients who For more information or to inquire about frequency coupling in the primary motor cortex received direct infusion of gene therapy enrolling a patient, call: (415) 353-2071 of Parkinson disease patients. Presented at into the putamen revealed that the drug This research has been supported by the the Society for Neuroscience Annual Meeting; did not cover the entire putamen as Michael J. Fox Foundation. Clinical PI: October 13-17, 2012; New Orleans, LA. was planned, but instead only covered Paul Larson MD; Coordinating PI: Krystof about 15% of the structure, implying that Bankiewicz MD, PhD; Neurology Co- patients did not receive the desired dose Intraoperative lateral PI:Chadwick Christine, MD. fluoroscopy showing of genetic material. an electrocorticography electrode inserted over ClearPoint allows real-time visualization of primary motor cortex during deep brain delivery to ensure that a sufficient amount stimulator implantation. of infusate spreads throughout the target

faculty

Movment Disorders Surgery Movement Disorders Research Laboratories Philip Starr MD, PhD Philip Starr MD, PhD Krystof Bankiewicz MD, PhD Edward Chang MD Basal ganglia physiology in Gene therapy and drug-delivery strategies movement disorders; neurogenesis Paul Larson MD Paul Larson MD and functional recovery Daniel Lim MD, PhD Neurotransplantation strategies for Parkinson’s disease movement disorders 16

Auditory Cortex

Clinical Trial of Deep Brain Larson PS, Cheung SW. Deep brain stimulation in area LC controllably triggers Stimulation for Tinnitus and auditory phantom precepts. Neurosurgery a New Paradigm for How 2012;70(2):398-405. Phantom External the Brain Perceives Sound This work has been nominated for the Modulators Awareness Permission UCSF is developing the first pilot study of Tsubokawa Award, given by the World deep brain stimulation (DBS) for patients Society for Stereotactic and Functional Area LC with the most severe forms of tinnitus who Neurosurgery to recognize important Dorsal Striatum have not been helped by other available publications published in the field of treatment modalities. functional and stereotactic neurosurgery. Gate Position The rationale for the study is based on UCSF Neurosurgery Hosts the work by UCSF neurosurgeon Paul Larson MD and otolaryngologist Steven Cheung 2012 Meeting of the American MD, which demonstrated stimulation in a Society for Stereotactic and Instruction newly discovered region of the caudate Signals Functional Neurosurgery Ventral Striatum nucleus called area LC could modulate Attentional loudness of auditory phantoms or create Under meeting chair Philip Starr MD, PhD Focus phantoms where none had previously and local arrangements host Daniel Lim Habit existed. The experiments were performed MD, PhD, the 2012 ASSFN meeting at Formation in patients undergoing DBS for movement the San Francisco Fairmont Hotel Nucleus Accumbens disorders who also had tinnitus. attracted record attendance (370), a record number of abstracts (170), and Area LC was not previously thought to be record corporate sponsorship. 16 involved in auditory perception, prompting a new model for how the brain perceives Keynote addresses were given by UCSF Distress Severity sound. Drs. Larson and Cheung propose faculty Karunesh Ganguly MD, Adam that the dorsal striatum – home to area Gazzaley MD, PhD and Peter Goadsby Limbic Cortex LC – gates the perception and loudness of MD, PhD. Paul Larson MD and Doris Wang auditory phantoms, and that control of the MD, PhD gave platform presentations. gate is modulated by the ventral striatum Edward Chang MD organized and and related circuits. moderated a satellite symposium on While most patients become accustomed electrocorticography in neuroscience to chronic tinnitus, 0.5% to 2% of patients research. Co-director of the UCSF surgical experience a drastic decrease in quality movement disorders program, Jill Ostrem Phantom percept gate control model. Conscious MD, organized a satellite symposium on awareness of auditory phantoms is contingent on of life, including emotional and behavioral associated corticostriatal signals passing through area problems. Understanding dorsal striatal programming of deep brain stimulators. LC of the dorsal striatum. Gate position is determined gate dysfunction may provide insight by restrictive integrity of area LC, strength of phantom precept neural representations, external modulators, into the biological underpinnings of how and the ventral striatum. atypical and typical tinnitus differ. © Wolters Kluwer Health pediatric neurosurgery 17 In a recent collaboration between the Pediatric Brain Tumor Center laboratories of David Rowitch MD, PhD and C. David James PhD, investigators found that while the BRAFV600E mutation is common in pediatric tumors, it did not form tumors from neural progenitor cells unless it was paired with homozygous deletion of cyclin-dependent kinase inhibitor 2A (CDK2A). The study, published this year in Proceedings of the National Academy of Sciences, also demonstrated that combination therapy of BRAF and CDK Human neural stem cells were injected into four sites of the brain in pediatric patients with inhibitors significantly extended survival in Pelizaeus-Merzbacher disease. a mouse model of pediatric astrocytoma. Another author of that report, pediatric neuro-oncologist Theodore Nicolaides MD, is now leading a UCSF study of Transplanted Neural Stem be performed in humans. Although only designed as a safety and preliminary single-agent vemurafenib (a BRAF inhibitor Cells Produced Myelin in efficacy study, additional evidence similar to PLX4720, which was used in the obtained from detailed MR diffusion data preclinical studies at UCSF) in children Phase I Trial V600E suggested that the transplanted cells are with BRAF mutant brain tumors. Future In one of the first neural stem cell able to produce new myelin in the white trials will focus on combination therapies, transplantation trials ever conducted in matter. These results are encouraging and the most promising being a combination the United States, a team led by Chief support the conduct of future studies. of vemurafenib and the CDK 4/6-specific of Pediatric Neurosurgery Nalin Gupta inhibitor PD0332991. MD, PhD and Chief of Neonatology David Gupta N, Henry RG, Strober J, Kang SM, Rowitch MD, PhD showed that neural Lim DA, Bucci M, Caverzasi E, Gaetano The clinical trial of vemurafenib has stem cells successfully engrafted into L, Mandelli ML, Ryan T, Perry R, Farrell J, been added to the next phase of UCSF’s the brains of patients and appear to have Jeremy RJ, Ulman M, Huhn SL, Barkovich AJ, Specialized Program of Research produced myelin. Rowitch DH. Neural stem cell engraftment and Excellence (SPORE) for Brain Tumors myelination in the human brain. Sci Transl Med. (it is supported by NIH bridge funding In the landmark phase I trial, human neural 2012;4(155):155ra137. that supports SPORE research between stem cells developed by Stem Cells, project periods). The trial will be part of the Inc., of Newark, California, were injected first pediatric project of any NIH SPORE directly into the frontal lobes of four young New Personalized Medicine program for brain tumors. boys with an early-onset, often fatal form Trials for Patients with The preclinical research was supported by of Pelizaeus-Merzbacher disease (PMD). Pediatric Astrocytomas In patients with PMD, oligodendrocytes the Pediatric Brain Tumor Foundation. V600E are unable to form myelin, leading to In recent years the BRAF mutation Huillard E, Hashizume R, Phillips JJ, Griveau A, progressive neurological deterioration. has been established as a promising Ihrie RA, Aoki Y, Nicolaides T, Perry A, Waldman therapeutic target in pediatric brain tumors The study, published in Science T, McMahon M, Weiss WA, Petritsch C, James because it is activated in approximately CD, Rowitch DH. Cooperative interactions Translational Medicine, demonstrated that 20% of pediatric tumors but only 3% of neural stem cell transplantation could of BRAFV600E kinase and CDKN2A locus adult tumors. deficiency in pediatric malignant astrocytoma as a basis for rational therapy. Proc Natl Acad Sci USA 2012;109(22):8710-5.

faculty Pediatric Neurological Surgery Pediatric Neuro-Oncology Mitchel Berger MD Nalin Gupta MD, PhD Anuradha Banerjee MD, MPH Ronald Shallat MD Kurtis I. Auguste MD Sabine Mueller MD, PhD Peter P. Sun MD Theodore Nicolaides MD Michael Prados MD pediatric neurosurgery 18 faculty

Pediatric Research Laboratories

Arturo Alvarez-Buylla PhD analysis of mutant epidermal growth factor Joanna Phillips MD, PhD developmental neuroscience; receptors in malignant gliomas; rodent neuropathology; interatction between stem-cell neurobiology model testing of experimental therapies tumor cells and microenvironment John Fike PhD Theodore Nicolaides MD David Rowitch MD, PhD neurogenesis and radiation injury BRAF oncogenesis in pediatric CNS tumors central nervous system development and tumorigenesis Nalin Gupta MD, PhD Anders Persson PhD Co-director, neural precursors of pediatric brain tumors William Weiss MD, PhD Pediatric Brain Tumor Research Center molecular basis of medulloblastoma pediatric brain tumor biology; Claudia Petritsch PhD cell-cell interactions; drug- brain cancer stem cells; asymmetric stem delivery strategies cell division; novel tumor suppressor genes C. David James PhD, Co-director, Pediatric Brain Tumor Research Center molecular biology of CNS cancer;

Pacific Pediatric Neuro- many PNOC trials are surgically based to validate target inhibition and build a Oncology Consortium: database of tissue for further research a New Clinical Trials Group on rare types of pediatric brain cancer. for Pediatric Brain Tumors Each institution also has scientists actively engaged in laboratory research on pediatric The Pacific Pediatric Neuro-Oncology tumor biology who work with clinicians to Consortium (PNOC) is a new network of turn their findings into therapies. eight children’s hospitals that conduct clinical trials of new therapies for children The first PNOC trial will test the mTOR with brain tumors. inhibitor everolimus to determine if it is more effective in patients with abnormal Led by neuro-oncologists Michael Prados activation of the PI3K/Akt/mTOR cell- MD and Sabine Mueller MD, PhD at UCSF, signaling pathway. The trial is open to the consortium focuses on developing patients with recurrent low-grade glioma. personalized medicine that exploits the specific aberrations found in each For more information about upcoming patient’s tumor. trials, visit: www.pnoc.us The hospitals that make up PNOC are home to some of the most experienced pediatric neurosurgeons in the nation, and

Parcticipating PNOC Sites: UCSF Benioff Children’s Hospital University of California, San Francisco* Seattle Children’s Hospital University of Washington Seattle Children’s Hospital Los Angeles Dorenbecher Children’s Hospital UCLA Mattel Children’s Hospital Oregon Health + Science University University of California, Los Angeles University of Utah Rady Children’s Hospital San Diego University of California, San Diego Children’s Hospital & Research Center Oakland * Operations and Data Management Center 19 The PBTF Institute Research Projects: Spatial, Temporal and Cellular Origins of Pediatric Glioma Principal Investigators: David Rowitch MD, PhD and Arturo Alvarez-Buylla PhD MYCN and Medulloblastoma Tumorigenesis Principal Investigator: William Weiss MD, PhD Genetics and Biology of Diffuse Intrinsic Pontine Gliomas Principal Investigators: Nalin Gupta MD, PhD; Joanna Phillips MD, PhD; and C. David James PhD Chief of Pediatric Neurological Surgery Nalin Gupta MD, PhD (left) with 2012 Pediatric Brain Tumor Foundation lecturer, James Olson MD, PhD (right).

Pediatric Brain Tumor to facilitate education on important topics During surgery, techniques such as Foundation Renews Support related to pediatric brain tumor treatment electrocorticography and brain mapping and research. are used to identify and avoid injury to for Institute at UCSF sites of language, motor, and sensory This year, the Pediatric Brain Tumor Center Children with Medically function during surgery. By placing at UCSF was awarded an additional three Refractory Epilepsy May electrodes directly on the brain and years of funding from the Pediatric Brain monitoring its activity, the pediatric Tumor Foundation (PBTF) as one of three be Candidates for epilepsy surgery team can more accurately PBTF Institutes in North America. Permanent Resolution locate the origin of a patient’s seizures than they could with a grid placed on the The PBTF was founded by Mike and of Seizures by Surgery scalp. This method represents the gold Dianne Traynor in 1991, and their tireless Approximately 15% of children with standard for defining the epilepsy network. efforts transformed the foundation into the epilepsy have symptoms that cannot A large number of surgical procedures world’s largest philanthropic organization be controlled with medication. At UCSF, for pediatric epilepsy are offered, dedicated to supporting the search for the patients who do not respond after being including hemispherectomy, corpus causes of and cures for childhood brain treated with two different medications callosotomy, vagal stimulation, temporal cancer. Sadly, Dianne passed away this are assessed by pediatric epileptologists, lobectomy, extratemporal resection, and year. Mike predeceased her in 2009. neuropsychologists, and pediatric subpial resection. To honor their memories, each year UCSF neurosurgeons to determine whether invites an expert on pediatric brain tumors or not they would be good surgical to give a lecture to the campus community candidates. With successful surgery, children are often seizure free for life.

Facts on Pediatric Epilepsy Surgery surgery to provide more detailed • fMRI techniques are being information about the location and incorporated into clinical use • Fifty percent of pediatric patients increase the safety of surgery. to provide a noninvasive method who undergo surgery for epilepsy of localizing language and motor • Because younger children usually have their seizures controlled. centers in the brain. These techniques have a greater chance of functional help reduce the likelihood of new • If seizure foci are located in recovery, an early referral for neurologic deficits resulting from eloquent cortex, subdural grids surgery is best. can be used to map the foci during the operation. center for management & surgery of peripheral nerve disorders faculty Michel Kliot MD Tractography allows neurosurgeons to view functioning axons along the surface of a nerve sheath tumor (left) and loss of function in a severed ulnar nerve (right).

Functioning Axons Sprout nerve. This novel approach was inspired New Developments in by the side-to-side vascular repairs to Site of Nerve Injury in performed by Michael Lawton MD, Neuro-Imaging Improve New Surgical Procedure chief of vascular neurosurgery. Diagnosis and Treatment Developed at UCSF of Peripheral Nerve Disorders Multidisciplinary Clinic Chief of Peripheral Nerve Surgery, Diffusion Tensor Imaging Michel Kliot MD, has developed a new for Neurofibromatosis surgical procedure to regenerate axons Patients with neurofibromatosis (types Neuroradiologists Cynthia Chin MD in damaged nerves. Called “side-to-side 1 and 2) are predisposed to a number of and William Dillon MD are currently neurotization,” it involves placing an intact CNS tumors, including peripheral nerve using diffusion tensor imaging (DTI) of nerve alongside the damaged nerve to tumors. This year UCSF began offering the peripheral nervous system to allow axons in the functioning nerve to a clinic staffed by specialists in neuro- visualize axons within peripheral nerves. sprout to the site of injury. By making oncology, neurosurgery, neuropathology, This cutting-edge technology is allowing small incisions in the side of each nerve, and neurology to evaluate patients with UCSF neurosurgeons to visualize: which avoids cutting across axons and neurofibromatosis and CNS tumors. • where functioning nerve fibers are potential axonal pathways, Dr. Kliot and located on the surface of a nerve his colleagues create a ‘window’ for the The new neurofibromatosis clinic also sheath tumor to avoid damaging functioning axons to branch out and enter partners with medical geneticists at the them during surgery the damaged nerve through. UCSF NF/Ras Pathway Clinic, which provides unique care for patients with • the extent of nerve fiber damage Standard surgical treatment for this type of syndromes causing germline mutations in injured nerves and any signs of injury is to cut and graft a normal nerve onto in genes encoding components of the spontaneous regeneration, resulting an injured nerve, which produces some Ras/mitogen activated protein kinase in fewer exploratory surgeries. damage in the normal nerve and prevents (MAPK) pathway. or reduces the chance for spontaneous DTI is also being used to monitor axon regeneration in the injured nerve. Treatment plans for individuals with regeneration following brachial plexus neurofibromatosis are developed through birth injury and to determine if certain The first patient to undergo side-to-side coordinated care that takes into account nerve roots have been pulled out, or neurotization at UCSF in July 2012 has the underlying biology as well as the avulsed, from the spinal cord and can regained some function mediated by severity and phenotype produced by the no longer be used for repair. If DTI shows axons from both the injured and intact specific mutation in the NF1 or NF2 gene. axons to be regenerating, exploratory

Pediatric brachial plexus injuries are treated by both pediatric and nerve injury specialists. 21

Ultrasound guidance demonstrates the right tibial nerve entering and exiting a tumor.

surgery may be unnecessary. Infants and room by allowing neurosurgeons to more children with brachial plexus nerve injuries precisely identify nerve pathology and are evaluated by specialists at UCSF’s plan surgical trajectories that minimize pediatric nerve injury clinic in collaboration incision length and tissue dissection, with Nalin Gupta MD, PhD, chief of thereby reducing operative time and pediatric neurosurgery. postoperative discomfort.

MR Diffusion Research Program on Nerve

A new application for MR diffusion imaging Sheath Tumor Quiescence Sutures on the surface of a resected nerve sheath tumor may allow physicians to non-invasively serve as markers of 3D orientation for neuropathologists The majority of nerve sheath tumors do determine whether nerve sheath tumors correlating MR diffusion imaging with histology. not grow beyond their size at initial are benign or malignant. In preliminary diagnosis and many can be monitored studies at the Center for Management and with serial imaging. A minority of these Surgery of Peripheral Nerve Disorders, tumors continue to grow and require tumors with high cellularity (often surgery, with a small number progressing to corresponding to greater malignancy) malignant tumors. UCSF neuropathologist were shown to have low diffusion Tarik Tihan MD, PhD, biochemist Joseph coefficients. Clinical research is currently DiRisi PhD, and neurosurgeons Michel ongoing to precisely correlate findings Kliot MD and Andrew Parsa MD, PhD from MR imaging with histopathology. are comparing tissue from growing and Intraoperative Ultrasound nongrowing benign nerve sheath tumors to characterize molecular differences that UCSF neurosurgeons use a portable may explain their different natural histories. ultrasound machine when diagnosing Understanding why many nerve sheath nerve injuries. Ultrasound is playing an tumors stop growing on their own could help increasingly important role in the operating develop new anti-proliferation strategies.

A dumbbell-shaped tumor of the left C5 nerve, which has stayed the same size for 19 years (Left: MR image from 1993; Right: MR image from 2010). Physicians at UCSF are trying to understand why most nerve sheath tumors stop growing on their own in order to induce quiescence in tumors that continue to proliferate and spread. surgical pain management program 22

faculty Edward Chang MD Philip A. Starr MD, PhD Glossopharyngeal neuralgia is a condition that causes severe pain in the tongue, throat, ear and tonsils.

Glossopharyngeal Neuralgia: nerve, but did not appear to be causing significant compression. After carefully Case Report identifying and then protecting the motor rootlets of the vagus nerve and Treating Physician: Edward Chang MD spinal accessory nerve using electrical stimulation, the glossopharygeal nerve Presentation was transected, as well as the sensory A 46-year-old woman presented with branches of the vagus nerve. long-standing intractable mouth pain for two years. She initially thought it was tooth Postoperative Course pain; however, it progressed to include The patient was pain-free after surgery. severe throat and ear pain. The episodes She experienced transient dysphagia, were triggered by eating, brushing teeth, which improved to baseline in two weeks. talking, and occasionally by sounds. The pain was described as sharp, lancinating, Glossopharyngeal neuralgia is a condition and shock-like — and, therefore, extremely in which there are repeated periods of debilitating. She tried several medications severe pain in the tongue, throat, ear, and including gabapentin, carbamazepine, and tonsils, which can last from seconds to a lamotrigine, which helped temporarily, but few minutes. In most cases, the source also caused significant side effects. of irritation is never found. The most effective drugs are usually anti-seizure Surgery medications. In severe cases, surgery can be performed to take pressure off the The patient decided to proceed with nerve (microvascular decompression) or to surgery to treat her pain. Intraoperatively cut the nerve (rhizotomy). Both surgeries the PICA artery was found directly are considered highly effective. adjacent to the glossopharyngeal

Intraoperative photograph showing the ‘neurovascular conflict’ prior to microvascular decompression for glossopharyngeal neuralgia.

UCSF is home to one of the largest and designated as a Clinical Center of most comprehensive pain neurosurgery Excellence by the American Pain Society centers in the United States. Patients – to design a therapeutic course that is receive extensive assessments to tailored to each patient. Through the use determine if they are candidates for of specialized surgical procedures, we surgical intervention for their disorders are often able to deliver pain control in severe cases. Neurosurgeons at UCSF work with a variety of other pain specialists at the UCSF Pain Management Center – neurospinal disorders 23 faculty Christopher Ames MD Dean Chou MD Praveen Mummaneni MD Philip Weinstein MD Michel Kliot MD (chiari malformation)

surgery. While some patients with severe deformities and major instability may require further fusion, a recent analysis by UCSF neurosurgeon Dean Chou and colleagues has shown that patients who have degeneration but good spinal alignment following surgery may not need an additional operation. No previous studies have compared nonoperative and operative management for this patient population. The authors conclude that in the absence of severe disability, nonoperative therapy should be considered as first-line treatment for adjacent segment pathology.

Chou D, Dekutoski M, Hermsmeyer J, Norvell DC. The treatment of lumbar adjacent segment pathology after a previous lumbar surgery: a systematic review. Spine (Phila Pa 1976) 2012;37(22 Suppl):S180-8. Neurosurgeon Praveen Mummaneni MD reviews the spinal pathology of his patient with his surgical team before operating. Anterior Cervical Discectomy and Fusion Shown to be a Hospitals Overestimate spaced out during several weeks, and the subsequent surgeries are currently defined Cost-Effective Procedure Readmission Rates for Spine as readmissions. Surgery: An Important Issue A five-year follow-up of 352 patients Neurosurgeons Praveen Mummaneni MD, receiving anterior cervical discectomy for Assessing Quality of Care Christopher Ames MD, and Dean Chou and fusion demonstrated that the Neurological and orthopaedic surgeons MD contributed to the report, presented at procedure was effective at relieving at UCSF reviewed thousands of hospital the 2012 Annual Meeting of the American spinal cord compression and provided a admissions for spine problems between Association of Neurological Surgeons. durable response. Cost analysis showed that a successful procedure was more 2007-2011 and analyzed “all cause” Amin BY, Tu T-H, Schairer WW, Na L, cost effective at five years than other readmissions, the basis for the Centers Takemoto S, Berven S, Deviren V, Ames C, nonsurgical interventions, such a physical for Medicare and Medicaid metric. Chou D, Mummaneni P. Ptifalls of calculating therapy or injections. Readmission rates can be used to hospital readmission rates based on determine a hospital’s quality of care nonvalidated administrative data sets. This work, published in Spine, received and reimbursements, as they can often J Neurosurg, In Press. the first-place award for a clinical research reflect hospital-acquired infections paper at the 2012 annual meeting of the or surgical complications. The UCSF Treating Adjacent Lumbar Cervical Spine Research Society. investigators found that readmissions Pathology After Previous Carreon LY, Anderson PA, Traynelis VC, were being overestimated by up to Lumbar Surgery Mummaneni PV, Glassman SD. Cost 25% because “all cause” readmissions effectiveness of single-level anterior cervical include planned staged surgeries. Many Patients who require fusion of the lumbar discectomy and fusion five years after surgery complex spinal surgeries are scheduled spine will often experience a break down [published online ahead of print September 13, to be performed in two or more stages in the adjacent level of their spine following 2012]. Spine (Phila Pa 1976). 2012 Sep 13. doi: 10.1097/BRS.0b013e318273aee2 24

Visual representation of the technique used to measure cervical lordosis (left) and cervical sagittal vertical axis (right). Cervical malalignment results in worse outcomes following cervical fusion surgery.

Standing Regional Cervical Tang JA, Scheer JK, Smith JS, Deviren V, Identifying Patients at Risk Bess S, Hart RA, Lafage V, Shaffrey CI, Sagittal Alignment Impacts Schwab F, Ames CP; ISSG. The impact of for Surgical Site Infection Outcomes After Cervical standing regional cervical sagittal alignment Surgical site infection is often used as a Fusion Surgery on outcomes in posterior cervical fusion measure of health care quality at large surgery. Neurosurgery 2012;71(3):662-9. hospitals. A recent analysis by spine In a landmark paper published in neurosurgeons and orthopaedic surgeons Neurosurgery this year, Christopher Ames Minimally Invasive Techniques at UCSF used administrative claims data MD and his colleagues showed that better for Severe Spinal Deformity to identify the patient population most at sagittal alignment of the cervical spine risk for developing surgical site infection is correlated with better health-related at All Levels following spine surgery. The investigators quality-of-life scores after cervical spine identified a series of procedural and fusion surgery. This study was the first to UCSF is currently offering minimally invasive procedures to treat severe patient-based risk factors, which will help show that cervical alignment is linked to to counsel high-risk patients before surgery. outcomes in the same way that lumbar deformity caused by kyphosis or scoliosis. sagittal balance is linked to outcomes Improvements in instrumentation are Abdul-Jabbar A, Takemoto S, Weber MH, after lumbar fusion surgery. allowing neurosurgeons to perform the Hu SS, Mummaneni PV, Deviren V, Ames same operations previously done through CP, Chou D, Weinstein PR, Burch S, Berven As a result of this study, neurosurgeons at open procedures through a minimally SH. Surgical site infection in spinal surgery: UCSF now obtain standing preoperative invasive approach. description of surgical and patient-based and postoperative cervical radiographs risk factors for postoperative infection using and 3-foot standing films of all patients These operations include vertebral column resection for severe rigid administrative claims data. Spine (Phila Pa undergoing cervical spine fusion. 1976) 2012;37(15):1340-5. This allows them to better plan ideal deformity and vertebrectomy for tumors postoperative cervical alignment. that are causing collapse of the spine or deformity. Minimally invasive approaches This work was presented as a plenary for these conditions have resulted in talk at the Joint Section on Spine and less blood loss and lower infection rates Peripheral Nerves at the 2012 Annual among UCSF patients. Meeting of the American Association of Neurological Surgeons.

“Major operations for deformity were the last frontier for minimally invasive surgery.” – Dean Chou MD neurospinal disorders 25 55 <45 50 * * 46-64 45 * >65 40

ODI 35 * 30

25

20 preop 3 month 6 month 1 yr 2 yr

Comparisons in Oswestry Disability Index scores by age groups following surgery for correction of severe deformity. *=significant difference from ≤45-year-old group; ∆ = significant difference from 46 to 64-year-old group.

Elderly Patients Have Ames CP, Scheer JK, Smith JS, Gupta MC, Klineberg E, Hart RA, Burton DC, Hostin R, Better Health-Related Obrien MF, Shaffrey CI, Bess S, Schwab F, Quality of Life After Major Deviren V, Kebaish K, International Spine Study Deformity Surgeries Group (ISSG). Outcomes following three- column spinal osteotomies: impact of HRQOL Health-related quality-of-life (HRQOL) and age on two-year follow up. Presented outcomes for elderly patients needing at the 47th Annual Meeting of the Scoliosis major surgery to correct severe Research Society; September 5-8, 2012; deformities have not been well Chicago, IL. characterized despite an increasing number of elderly patients seeking New Clinic for treatment for rigid iatrogenic deformities. Chiari Malformation In a study done this year by the The Department of Neurological Surgery International Spine Study Group, has opened a specialized clinic to evaluate investigators analyzed the relationship patients with Chiari malformation, which between age and HRQOL for 228 patients is often characterized by low-lying who underwent three-column osteotomies cerebellar tonsils. By using cine MRI pulse – such as pedicle subtraction osteotomies sequences to evaluate cerebrospinal fluid and vertebral column resections. (CSF) flow dynamics, physicians are able Interestingly, they found that while elderly to accurately determine whether there is patients take longer to recover from an obstruction of flow between the brain surgery, they achieve greater improvement and cervical spinal cord. Many patients in their HRQOL than younger patients. who meet the anatomical criteria for Chiari malformation (cerebellar tonsillar descent UCSF neurosurgeon Christopher Ames below the foramen magnum) do not have MD presented these findings in the plenary blockage of CSF flow. At UCSF, cine MRI session of the annual meeting of the studies are a requirement for all patients in Scoliosis Research Society. order to prevent unnecessary surgeries. neurosurgery patient safety & quality improvement program faculty Catherine Lau MD Rita Mistry MPH

In 2012, the Department of Neurological at improving the quality of neurosurgical • Fostering a culture of patient safety Surgery received the Healthgrades patient care and the patient experience at and promoting improved communication Neurosurgery Excellence Award, which UCSF Medical Center. within the perioperative setting. recognizes hospitals for superior patient Find the video under the Quality & safety outcomes in neurological surgery. Creating a Culture of Safety Safety section of our website: The Department of Neurological Surgery’s Within Operative Neurosurgery neurosurgery.ucsf.edu Patient Safety and Quality Improvement This year, the Department of Lau CY, Greysen SR, Mistry RI, Han SJ, Program was formed in 2011 to provide Neurological Surgery, in collaboration Mummaneni PV, Berger MS. Creating a culture the safest and highest quality patient with the Department of Anesthesia and of safety within operative neurosurgery: the care based on the principles of clinical, perioperative nursing staff, developed an design and implementation of a perioperative operational, and academic excellence educational video on critical perioperative safety video. 2012;33(5):E3. with the overall aim of being a national Neurosurg Focus safety TIME OUT and debrief checklists leader in neurological surgery quality and for surgical team members to review patient safety. National Neurosurgery Quality prior to and immediately after a surgical Led by Catherine Lau MD and Rita Mistry procedure. The video focuses on: and Outcomes Database MPH, the program is made up of a multi- Beginning in 2013, the Department of • Minimizing errors and improving disciplinary team of faculty members, Neurological Surgery will submit data patient outcomes by simplifying residents, nurse practitioners, physician to the National Neurosurgery Quality and standardizing neurosurgical assistants, clinic practice managers, and Outcomes Database (N2QOD), perioperative patient safety practices nurses, pharmacists, Infection Control sponsored by the American Association and team communication processes. specialists, Service Excellence liaisons, of Neurological Surgeons/ NeuroPoint and Medical Center quality improvement • Highlighting critical patient safety Alliance. This is the first nationwide effort and service line representatives. Together, checks/precautions (e.g., patient to collect data on safety, quality, and cost- they work on a multitude of projects aimed identification, TIME OUT) and team effectiveness in the field of neurosurgery. communication practices (e.g., debriefs, hand-offs).

Our educational video “Creating a Culture of Safety Within Operative Neurosurgery” highlights team communication, as well as the critical perioperative safety TIMEOUT and debrief checklists for surgical team members. 27

Four Key Areas of Focus in the Neurosurgery Patient Safety and Quality Improvement Program

Clinical Effectiveness Patient Experience • Reduce craniotomy and • Improve inpatient HCAHPS spine surgical site infections and Press-Ganey scores • Reduce medication errors • Improve outpatient HCAHPS and Press-Ganey scores • Reduce other hospital-acquired conditions: post-op VTE, CA-UTI, Resident Engagement VAP, CLABSI, HAPUs, falls • Quality Improvement (QI) • Lower mortality observed/ Resident Curriculum expected (O/E) ratios • Resident participation in case review • Improve hand hygiene rates and ongoing departmental QI projects • Reduce 30-day readmission rates • Quarterly QI Resident Lunches

Clinical Efficiencies • Annual participation in UCSF Graduate Medical Education QI Incentive Project • Improve discharge before noon • Improve discharge summary completion timeliness • Reduce unnecessary laboratory and radiologic testing ucsf neurological surgery community extension program

faculty Tarun Arora MD, Director Keith B. Quattrocchi MD, PhD, FACS Corey Raffel MD, PhD Archimedes Ramirez MD Jeffrey Yablon MD

Keith Quattrocchi MD, Jillian Payne NP, and Tarun Arora MD work with community physicians to provide high-quality outpatient and inpatient neurosurgical care in Marin, CA.

The Department of Neurological Surgery Napa Valley has formed partnerships with Marin General Hospital, Queen of the Valley At Queen of the Valley Medical Center Medical Center, and Good Samaritan in Napa Valley, Jeffrey Yablon MD and Hospital to provide extended services to Archimedes Ramirez MD treat patients Bay Area residents and physicians. with central nervous system tumors, spinal disorders, cerebrovascular disorders, Marin neurotrauma, minimally invasive spine surgery, spinal instrumentations, and In May 2012, Keith B. Quattrocchi MD, skull base surgery. Both Dr. Yablon and PhD, FACS joined Tarun Arora, director Dr. Ramirez have particular expertise in of the Community Extension Program, minimally invasive spine surgery and many at Marin General Hospital as a full- years of experience in trauma neurosurgery. time, locally based neurosurgeon. Drs. Quattrocchi and Arora, along with a San Jose specialty trained nurse practitioner, skilled outpatient clinic staff, and colleagues In January 2013, a new pediatric at Marin General, work together to neurosurgery clinic will open at Good seamlessly coordinate state-of-the-art Samaritan Hospital in San Jose, led by treatment with patients’ local medical care. renowned pediatric neurosurgeon Corey Raffel MD, PhD. Dr. Raffel joins us from Ohio State University, where he served as professor and vice chair. He has also UCSF Neurosurgery offers services at Queen of the Valley Medical Center in Napa Valley. served as chief of pediatric neurosurgery at Nationwide Children’s Hospital and been the principal investigator of several research programs aimed at finding new treatments for childhood brain tumors. Patients with highly complex or unusual disorders requiring the full multidisciplinary care of an academic medical center are offered treatment options at UCSF Medical Center. UCSF Department of Neurological Surgery Nonprofit Org. 505 Parnassus Avenue, 779 M U.S. Postage San Francisco, CA 94143-0112 PAID University of 32 California San Francisco

University of California San Francisco

Neurological Surgery

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