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  1. 1. volume 8 number 4 ucsf department of neurological surgery neurosurgery news academic and research news is nearly always relieved. While MVD is considered to be the most invasive surgery for trigeminal neuralgia, it is Gamma Knife plan for treatment of trigeminal neuralgia also the best procedure for correcting the underlying problem that usually causes trigeminal neuralgia: vascular compression. MVD also Surgical Options for Treating Facial Pain causes the least damage to the trigeminal nerve and provides, Facial pain comprises a group Trigeminal Neuralgia on average, the longest pain-free of complex and often poorly The first line of treatment for periods and the best chance for understood disorders that are patients with trigeminal neuralgia is a patient to be permanently off severely debilitating and often always medication. The drugs most medication. MVD has a long-term refractory to medical therapy. commonly used for treating trigeminal success rate of approximately The source of the pain can vary neuralgia are medications that were 80% as a stand-alone treatment. depending on the syndrome, originally developed for the treatment The procedure requires an average but symptoms are often similar, of epilepsy. However, carbamazepine hospital stay of two to three days, making correct diagnoses for and other drugs prescribed for and four to six weeks to return to facial pain especially challenging. trigeminal neuralgia do not always normal daily activities. Professor of Neurological Surgery, remain effective over time, requiring Nicholas Barbaro MD, is an expert Gamma Knife® Radiosurgery higher and higher doses or a greater in treating severe facial pain, number of medications taken Radiosurgical treatment for trigeminal including trigeminal neuralgia concurrently, and some patients neuralgia is the least invasive surgical and other neuropathic facial pain experience side effects serious option. The Gamma Knife is a device syndromes. “Occasionally patients enough to warrant discontinuation. that delivers precise, controlled are misdiagnosed,” says Barbaro. These patients may be candidates beams of radiation to targets inside “Some physicians group all facial for surgical pain intervention. the skull, including the brain or pain under the umbrella of trigeminal UCSF offers multimodality surgical associated nerves. For trigeminal neuralgia, but trigeminal neuralgia is treatments chosen for the needs of neuralgia treatment, the radiation a specific condition that has highly each patient. beams are aimed at the trigeminal effective and specific treatments.” nerve where it enters the brainstem. Some treatments that are effective Microvascular Decompression Gamma Knife treatment does not for trigeminal neuralgia can actually Microvascular decompression (MVD), target the root cause of trigeminal worsen trigeminal neuropathic pain. also known as the Janetta procedure, neuralgia, but instead damages the The Department of Neurological is the most common surgical trigeminal nerve in a controlled way Surgery treats patients from all over procedure for the treatment of to stop the transmission of pain the Western United States, and trigeminal neuralgia. In most cases, signals. The procedure requires little Barbaro and his team review records there is a blood vessel (typically or no anesthesia, and is performed and, if necessary, conduct telephone an artery, but sometimes a vein) on an outpatient basis. This interviews to determine if patients compressing the trigeminal nerve. procedure provides significant pain can be helped before they travel to By moving this blood vessel away control or reduction in approximately San Francisco for treatment. from the nerve and interposing a 80% of patients, but response padding made of Teflon felt, the pain is usually slower than for other cont. on page 3 Branch of superior cerebellar artery compressing the trigeminal nerve in a patient with trigeminal neuralgia University of California Department of Neurological Surgery San Francisco University of California, San Francisco 400 Parnassus Avenue, 8th Floor Box 0350 San Francisco, CA 94143-0350 Phone: 415/353-7500 Neurological Surgery Fax: 415/353-2889
  2. 2. looking to the future Pain is one of the most universal treatment of chronic pain that experiences and a condition that included percutaneous cordotomy, all of us as medical professionals medullary tractotomy, dorsal- come up against, regardless of column stimulation, and thalamic our specialty. While many types and internal-capsule stimulation for of pain can be managed with thalamic and paraplegia pain. By medications, debilitating pain 1978, percutaneous dorsal-column refractory to medical treatment stimulation was largely abandoned can be complex and especially as ineffective in 70% of cases, and difficult to diagnose and treat. Many deep brain stimulation was used for patients will need life-long care by relieving thalamic pain, anesthesia a multidisciplinary group able to dolorosa, and intractable low Our colleagues in the American offer ongoing therapies, ranging back pain. Association of Neurological from psychological to surgical. The Surgeons/Congress of Neurological Deep brain stimulation continues to relevance of neurological surgery in Surgeons Joint Section on Pain have be explored as a treatment for pain, pain management is inherent in the expressed concern over the waning and investigators at UCSF, led by way transmission of pain signals interest in pain medicine due to Philip Starr MD, PhD, have published occur through the central nervous lower level reimbursements and the one of four open-label series of system. Through the development of difficulty in managing this patient deep brain stimulation for cluster specialized surgical procedures, from population. But it is important to note headache – the most severe form intrathecal opiate pumps to spinal that this can also be one of the most of primary headache, in which 10 to cord stimulators, neurosurgeons rewarding patient populations; one 20% of cases are unresponsive to have long played a major role in in which it is possible to dramatically medical therapy. The results of these delivering pain control. improve quality of life and relieve four series indicate that 50 to 70% suffering. At the Department of At UCSF, the history of break- of patients experience substantial Neurological Surgery, our faculty throughs in pain treatment began relief of their headache symptoms work with a variety of other pain in 1958 with John Adams MD, one to four years following surgery. specialists at the UCSF Pain then chair of the Department of While cluster headache is not yet Management Center to design a 2 Neurological Surgery, who used an approved indication for deep therapeutic course for pain control hypophysectomy to treat pain brain stimulation, the initial results that is tailored to each case. It is our resulting from metastatic breast are promising and warrant further mission to ensure that no patient cancer and prostate cancer. In investigation in controlled clinical lives with uncontrolled pain. 1971, another chair, Charles trials. As many, but not all, patients Wilson MD, also found that with cluster headaches respond to hypophysectomy gave significant deep brain stimulation, it will also relief of pain to two thirds of be important develop a method to patients with metastatic breast prospectively identify those patients cancer. Other types of surgeries for most likely to benefit. It has also intractable pain performed during recently been found that occipital the 1960s and 1970s included nerve stimulation provides results thalamotomy and radiofrequency similar to deep brain stimulation, Mitchel S. Berger MD, electrode implantation, and and our functional neurosurgery Kathleen M. Plant research explored stimulating the group currently suggests offering Distinguished Professor & Chairman brain’s own endorphin-mediated this approach prior to treatment analgesia system, which modulates with deep brain stimulation. Director, Brain Tumor pain and can be activated by Research Center Although neurosurgeons have an external manipulations. In July Department of important role in pain management, 1969, Yoshio Hosobuchi from the Neurological Surgery, UCSF fewer neurosurgical residents University of Chicago joined the are entering this subspecialty. faculty, starting a program for the
  3. 3. Flouroscopic image of radiofrequency needle inserted into the trigeminal cistern Frameless stereotactic magnetic resonance image with superimposed position of motor cortex stimulation electrodes Surgical Options for Treating Facial Pain cont. from page 1 treatments. Patients usually respond Neuropathic Facial Pain neuropathic pain. More widespread within four to six weeks following use of motor cortex stimulation Non-trigeminal neuralgia neuropathic treatment; however, some patients began in the early 1990s after a facial pain may be caused by require as long as three to eight series of clinical experiments by trigeminal nerve injuries occurring months for the full response. Most Tsubokawa et al. demonstrated its during dental procedures or following patients remain on full doses of long-term efficacy in controlling pain. trauma to the skull or face, or it medication for at least three months may be idiopathic. A variety of In motor cortex stimulation surgery after treatment. medications may be used, and some for neuropathic facial pain, the Radiofrequency Lesion patients may respond sufficiently to electrode’s power source is kept avoid invasive procedures. In many externally for up to three days and Radiofrequency lesion (RFL) is a cases, the injured nerves will heal is hooked up to a pulse generator. good option for treating severe pain over time, although this may take There is a 50 to 70% success rate in high-risk patients, such as those several years. Patients with facial with this procedure. If the trial with concurrent illness that would 3 pain that is not sufficiently reduced electrode is successful, the pulse make an open surgical procedure too by medications may be candidates generator is implanted under the dangerous. It is also a good option for treatment with motor cortex patient’s skin to provide long-term for patients with multiple sclerosis, stimulation, which uses an electrode pain relief. Improvements in frameless whose trigeminal neuralgia is often placed over the face motor cortex stereotactic navigation techniques not caused by vascular compression. through a small craniotomy. ensure that the electrode is placed Like Gamma Knife treatment, RFL very accurately under general damages the trigeminal nerve to stop Motor cortex stimulation works in a anesthesia with a relatively small the transmission of pain signals. In way similar to spinal cord stimulation, craniotomy. Although the scientific RFL an electrode inserted through the which uses electrodes placed onto basis for pain relief with motor cortex cheek is used to heat the nerve and the lower spine to stimulate nerve stimulation is not well understood, cause selective damage to stop pain fibers and block the transmission the results represent a remarkable signals from traveling to the brain. of pain signals resulting in back or advance in treatment for specific The treatment provides immediate leg pain. The original testing was types of facial pain that are not pain relief in up to 90% of patients, to be done over the sensory cortex helped by other modalities. but can cause more facial numbness to see if the same result could be than the other procedures and has a obtained. However, the investigators pain recurrence rate of 40% at two to discovered that stimulation of the three years after surgery. If necessary, electrodes over the motor cortex the procedure can be repeated. was more effective at reducing
  4. 4. resident gazette Edward Chang MD is currently chief outcomes and also microsurgical resident of neurological surgery. approaches to eloquent and deep He received his undergraduate cavernous malformations. degree from Amherst College in Chang’s principal research goals Massachusetts, and attended are to understand the basic cortical medical school at UCSF where he mechanisms underlying speech graduated with AOA honors. In 2001, perception and production. In 2008, he was awarded a Howard Hughes he began a postdoctoral research Medical Institute fellowship. fellowship with Robert Knight MD selected publications As a neurosurgical resident, with at the Helen Wills Neuroscience Chang EF, Quigg M, Oh MC, Dillon WP, Ward MM, Nicholas Barbaro MD, Chang Institute at UC Berkeley. With Laxer KD, Broshek DK, Barbaro NM. Predictors of characterized the predictors of support from a NIH National efficacy after stereotactic radiosurgery for medial seizure remission after stereotactic Research Service Award fellowship, temporal lobe epilepsy. Neurology 2009, In Press. radiosurgery for epilepsy, and he used electrocorticography to Chang EF, Clark A, Jensen RL, Bernstein M, Guha A, Carrabba G, Mukhopadhyay D, Kim W, examined the outcomes of resective study the emergent representation Liau LM, Chang SM, Smith JS, Berger MS, surgery for epilepsy from tumors of categorical speech perception McDermott MW. Multiinstitutional validation of and cortical malformations. With in the human superior temporal the University of California at San Francisco Low-Grade Glioma Prognostic Scoring System. Philip Starr MD, PhD, he detailed gyrus. Chang was awarded the J Neurosurg 2009;111(2):203-210. the functional somatotopic Wilder Penfield Fellowship from the Chang EF, Potts MB, Keles GE, Lamborn KR, organization of the human globus Congress of Neurological Surgeons Chang SM, Barbaro NM, Berger MS. Seizure pallidus internus in patients with to develop a novel method of characteristics and control following surgical resection in 332 patients with low-grade dystonia. With Mitchel Berger MD, mapping brain dynamics using gliomas. J Neurosurg 2008;108(2):227-235. Chang documented the long-term electrocorticography. Chang EF, Turner RS, Ostrem JL, Davis VR, survival benefits of intraoperative Starr PA. Neuronal responses to passive Chang intends to pursue a stimulation mapping and extent of movement in the globus pallidus internus career in functional and epilepsy in primary dystonia. J Neurophysiol resection for low-grade gliomas. neurosurgery. His long-term 2007;98(6):3696-3707. With Michael McDermott MD, he research priorities are to discover Chang EF, Merzenich MM. Environmental noise devised a powerful prognostic retards auditory cortical development. Science the neurophysiologic substrates of 4 scoring system for low-grade 2003;300(5618):498-502. higher brain function in humans, gliomas, and later validated it in Chang EF, Wong RJ, Vreman HJ, Igarashi T, to elucidate their abnormalities Galo E, Sharp FR, Stevenson DK, a multi-institutional collaborative in cognitive and motor disorders, Noble-Haeusslein LJ. Heme oxygenase-2 cohort. With Michael Lawton MD, protects against lipid peroxidation-mediated cell and to develop novel restorative Chang reported seizure control loss and impaired motor recovery after traumatic strategies towards their remediation. brain injury. J Neurosci 2003;23(9):3689-3696. residents’ publications Bloch OG, Jian BJ, Yang I, Han SJ, Aranda D, Lim DA, Tarapore P, Chang E, Burt M, Chakalian L, Sughrue ME, Yang I, Kane AJ, Rutkowski MJ, Ahn BJ, Parsa AT. A systematic review of intracranial Barbaro N, Chang S, Lamborn KR, McDermott MW. Fang S, James CD, Parsa AT. Immunological chondrosarcoma and survival [published online Safety and feasibility of switching from phenytoin to considerations of modern animal models of ahead of print September 29, 2009]. J Clin Neurosci. levetiracetam monotherapy for glioma-related seizure malignant primary brain tumors. J Transl Med doi:10.1016/j.jocn.2009.05.003. control following craniotomy: a randomized phase II 2009;7(1):84. Chang EF, Gabriel RA, Potts MB, Garcia PA, pilot study. J Neurooncol 2009;93(3):349-354. Tate MC, Banerjee A, Vandenberg SR, Tihan T, Barbaro NM, Lawton MT. Seizure characteristics and Oh MC, Lim DA. Novel treatment strategies for Chi JH, Ames CP, Parsa AT. Post-radiation reactive control after microsurgical resection of supratentorial malignant gliomas using neural stem cells [review]. changes in a single vertebral body mimicking cerebral cavernous malformations. Neurosurgery Neurotherapeutics 2009;6(3):458-464. metastatic pineoblastoma. J Neurosurg Pediatr 2009;65(1):31-38. Potts MB, Adwanikar H, Noble-Haeusslein LJ. 2009;4(5):479-483. Clark AJ, Lee K, Broaddus WC, Martin MJ, Models of traumatic cerebellar injury. Cerebellum Tate MC, Aghi MK. Biology of angiogenesis and Ghatak NR, Grossman CE, Baker S Jr, Baykal A. 2009;8(3):211-221. invasion in glioma [review]. Neurotherapeutics. Primary brain T-cell lymphoma of the lymphoblastic Richardson RM, Ostrem JL, Starr PA. Surgical 2009;6(3):447-457. type presenting as altered mental status [published repositioning of misplaced subthalamic electrodes Yang I, Aghi MK. New advances that enable online ahead of print July 4, 2009]. Acta Neurochir in Parkinson’s disease: location of effective and identification of glioblastoma recurrence. (Wien). doi: 10.1007/s00701-009-0433-z. ineffective leads. Stereotact Funct Neurosurg Nat Rev Clin Oncol 2009;6(11):648-657. Clark AJ, Ware JL, Chen MY, Graf MR, Van Meter TE, 2009;87(5):297-303. Yang I, Sughrue ME, Han SJ, Aranda D, Pitts LH, Dos Santos WG, Fillmore HL, Broaddus WC. Effect of Richardson RM, Singh A, Sun D, Fillmore HL, Cheung SW, Parsa AT. A comprehensive analysis WT1 gene silencing on the tumorigenicity of human Dietrich DW, Bullock MR. Stem cell biology of hearing preservation after radiosurgery for glioblastoma multiforme cells [published online in traumatic brain injury: effects of injury and vestibular schwannoma [published online ahead ahead of print April 24, 2009]. J Neurosurg. doi: strategies for repair [published online ahead of print September 11, 2009]. J Neurosurg. doi: 10.3171/2008.11.JNS08368. of print June 5, 2009]. J Neurosurg. doi: 10.3171/2009.8.JNS0985. George PM, Saigal R, Lawlor MW, Moore MJ, 10.3171/2009.4.JNS081087. LaVan DA, Marini RP, Selig M, Makhni M, Burdick JA, Langer R, Kohane DS. Three-dimensional conductive constructs for nerve regeneration. J Biomed Mater Res A 2009;91(2):519-527.
  5. 5. Vincent Wang MD, PhD was born selected publications in the United Kingdom and was Chun KA, Manley GT, Stiver SI, Aiken AH, raised in Hong Kong. He moved to Phan N, Wang V, Meeker M, Cheng SC, Houston, TX when he was thirteen Gean AD, Wintermark M. Interobserver Variability years old and subsequently attended in the Assessment of CT Imaging Features of Traumatic Brain Injury [published online ahead the University of Houston, where he of print November 6, 2009]. J Neurotrauma studied Biology. After working as a doi:10.1089/neu.2009.1115. research assistant at M.D. Anderson Maricich SM, Xia A, Mathes EL, Wang VY, Cancer Center, he entered the MD/ Oghalai JS, Fritzsch B, Zoghbi HY. Atoh1-lineal neurons are required for hearing and for the PhD program at Baylor College of survival of neurons in the spiral ganglion and Medicine in 1996. At Baylor, Wang brainstem accessory auditory nuclei. J Neurosci 2009;29(36):11123-33. joined the Pediatrics laboratory of Huda Zoghbi MD and studied mouse Chou D, Wang VY, Gupta N. Transpedicular corpectomy with posterior expandable cage cerebellar development. He was placement for L1 burst fracture. J Clin Neurosci supported by an individual National In addition to his clinical interest 2009;16(8):1069-72. Research Service Award from the in neurosurgery, Wang has also Wang VY, Aryan H, Ames CP. A novel anterior NIH. At Baylor, he also worked developed an interest in the socio- technique for simultaneous single-stage anterior and posterior cervical release for fixed kyphosis. with Claudia Robertson MD and economic issues in healthcare. J Neurosurg Spine 2008;8(6):594-9. developed an interest in traumatic He has recently been selected as Wang VY, Manley G. Recognition of paroxysmal brain injury and neurocritical care. a resident fellow of the Council autonomic instability with dystonia (PAID) in a State of Neurological Surgery patient with traumatic brain injury. J Trauma Wang started his neurological surgery 2008;64(2):500-2. and will participate in organized residency in 2005 at UCSF. He joined Chou D, Lu D, Chi J, Wang V. Rib-head neurosurgery committees to osteotomies for posterior placement of expandable the laboratory of Geoffrey Manley address various socio-economic cages in the treatment of metastatic thoracic spine MD, PhD and studied the function tumors. J Clin Neurosci 2008;15(9):1043-7. issues in neurosurgery. He is also of aquaporin 4 in the control of water a member of the UCSF Medical efflux in mice during a hyperosmotic Center’s Utilization Management state. Through this project, he Committee. In addition to clinical developed an interest in the cellular practice, Wang is also interested in adaptive response to a hypertonic 5 using his experience in a hospital condition. He plans to continue administration role in the future. studying this area in the future. Nicholas M. of the UCSF Nerve Injury Clinic, a selected publications Barbaro MD, multidisciplinary clinic where patients focus on faculty Chang EF, Nagarajan SS, Mantle M, Barbaro NM, professor of with various types of injuries to Kirsch HE. Magnetic source imaging for the surgical neurological peripheral nerves are evaluated for evaluation of electroencephalography-confirmed secondary bilateral synchrony in intractable epilepsy surgery, has possible surgical treatment. As a [published online ahead of print July 3, 2009]. extensive member of the Neurospinal Disorders J Neurosurg. doi: 10.3171/2009.6.JNS081376. expertise in Program, Barbaro performs surgery Binder DK, Garcia PA, Elangovan GK, Barbaro NM. the treatment for adult Chiari malformations and Characteristics of auras in patients undergoing temporal lobectomy [published online ahead of disorders that for pain resulting from compression of print April 24, 2009]. J Neurosurg. doi: are manageable syndromes, such as thoracic outlet 10.3171/2009.3.JNS081366. by stereotactic and piriformis syndrome (extraspinal Barbaro NM, Quigg M, Broshek DK, Ward MM, and functional sciatica), previous trauma, tumor, Lamborn KR, Laxer KD, Larson DA, Dillon W, Verhey L, Garcia P, Steiner L, Heck C, neurosurgical infection, or inflammation. Kondziolka D, Beach R, Olivero W, Witt TC, techniques, Salanova V, Goodman R. A multicenter, prospective Barbaro also serves as the pilot study of gamma knife radiosurgery for including Neurological Surgery Residency mesial temporal lobe epilepsy: seizure response, epilepsy and adverse events, and verbal memory. Ann Neurol Program Director and has received chronic intractable pain syndromes. 2009;65(2):167-75. several teaching awards for He is co-director of the Functional Sughrue ME, Levine J, Barbaro NM. Pain as a his dedication in training future symptom of peripheral nerve sheath tumors: Neurosurgery Program and is academic neurosurgeons. He has clinical significance and future therapeutic recognized internationally for his directions. J Brachial Plex Peripher Nerve Inj lectured widely about epilepsy, work in epilepsy surgery. Barbaro 2008;3:6. movement disorders, surgical also has a special interest in Sanchez-Mejia RO, Limbo M, Cheng JS, Camara management of pain, and surgical Quintana J, Ward MM, Barbaro NM. Ronald Tasker surgical management of trigeminal management of peripheral nerve Award: retreatment of medically refractory trigeminal neuralgia, which may offer relief for neuralgia. Clin Neurosurg 2006;53:313-5. disorders throughout the United many patients who are not helped Brown JA, Barbaro NM. Motor cortex stimulation States and in Canada and Europe. by medical therapy. He is director for central and neuropathic pain: current status [review]. Pain 2003;104(3):431-5.
  6. 6. neurosurgery news & notes Manish Aghi MD, PhD, assistant the appearance of the disease. The are designed to support promising professor of neurological surgery, goal of this work is to pave the way new investigators, with the goal of has been awarded an American for clinical testing of the inhibitor advancing exceptionally innovative Brian Tumor Association Young and to develop a new model of research ideas. Investigator Award and a Parkinson’s disease that is not based Geoffrey Manley MD, PhD, professor Translational Research Grant for on neurotoxins. of neurological surgery, has been the project “Understanding distinct Edward Chang MD, chief resident awarded a $4 million GO grant by mechanisms of response to anti- in the Department of Neurological the NIH to build on a proposal to angiogenic therapy in glioblastoma”; Surgery, has been awarded a K99/ standardize data collection across an NIH/NINDS Independent R00 Pathway to Independence traumatic brain injury (TBI) studies, Scientist Award (K02) for the project Award by the National Institute of referred to as the TBI Common “Characterizing and targeting tumoral Neurological Disorders and Stroke. Data Elements (TBI-CDE). The TBI- factors recruiting perivascular This highly competitive funding CDE emphasizes demographics, progenitors”; and an American mechanism awards the most neuroimaging, outcome measures, Cancer Society Research Scholar promising researchers with up to biomarkers, and psychological Grant for the project “Defining and five years of substantial early career health. With funding from the GO targeting mechanisms of Avastin NIH support. His research seeks grant, a multi-center effort to validate resistance in glioblastoma.” to reveal the cortical circuitry the TBI-CDE will be performed at Mitchel S. Berger MD, Kathleen underlying higher cognitive behavior six medical centers. By developing M. Plant distinguished professor in humans, including language and infrastructure, refining standards and chair of neurological surgery, decision making. for data collection, and improving delivered a keynote address on TBI classification schemes, the John R. Fike PhD, professor of low-grade gliomas at the 2009 project is designed to tackle the neurological surgery, recently meeting of the World Federation major issues that have hampered collaborated with a group of of Neurosurgical Societies, held opportunities for translating investigators at UC Irvine to in Boston, Massachusetts. research into new treatments. transplant stem cells into the brains Krystof Bankiewicz MD, PhD, of rats that had undergone radiation The laboratory of S. Scott professor of neurological surgery treatment. The study found that Panter PhD, assistant adjunct 6 and Kinetics Foundation chair transplanted stem cells restored professor of neurological surgery, in translational research, John learning and memory to normal recently collaborated with the Forsayeth PhD, adjunct professor levels four months after radiotherapy. Alzheimer’s Research Center at of neurological surgery, and their In contrast, irradiated rats that did Regions Hospital to examine the colleagues have recently published not receive stem cells experienced effects of deferoxamine, a high- a landmark article in Neuroimage a more than 50 percent drop in affinity iron chelator, on ischemic on optimizing cannula placement cognitive function. stroke damage. They found that for infusions into the primate pretreatment with deferoxamine Acharya MM, Christie LA, Lan ML, putamen. Their image-guided administered intranasally could Donovan PJ, Cotman CW, Fike JR, Limoli system allows real-time visualization protect rats from stroke induced CL. Rescue of radiation-induced cognitive of infusions into the brain, which 48 hours later. Drug given after the impairment through cranial transplantation of enables neurosurgeons to carefully stroke significantly reduced tissue human embryonic stem cells. Proc Natl Acad monitor infusions of therapeutic damage. Intranasal delivery allows Sci USA 2009;106(45):19150-19155. agents and, if necessary, alter the the drug to bypass the blood-brain parameters or terminate the infusion. Daniel Lim MD, PhD, assistant barrier and enter the brain within professor of neurological surgery minutes. The pretreatment paradigm The Bankiewicz laboratory has also and director of restorative surgery, is relevant to patients undergoing received a $6 million grant from has been awarded a $600,000 bypass or any other vascular the NIH as part of a consortium of Sontag Foundation Distinguished surgery, and the post-treatment leading investigators to develop a Scientist Award to study how neural may be useful for stroke patients. new model of Parkinson’s disease stem cells can become cancerous. in monkeys. The work will deliver Hanson LR, Roeytenberg A, Martinez PM, He was also given a $1.5 million New a virus encoding a mutant kinase, Coppes VG, Sweet DC, Rao RJ, Marti DL, Innovator Award by the NIH to study LRRK2, which is a common cause Hoekman JD, Matthews RB, Frey WH 2nd, the gene expression “switches” in of familial Parkinson’s disease, in Panter SS. Intranasal deferoxamine provides developing neural stem cells. These order to precipitate the disease. increased brain exposure and significant switches progressively control the A small-molecule inhibitor of the protection in rat ischemic stroke. J Pharmacol specialization of the cells into the LRRK2 will then be delivered to Exp Ther 2009;330(3):679-686. multitude of cell types that form test its effectiveness in blocking the brain. New Innovator awards
  7. 7. UCSF Brain Tumor Research Center Receives Major Grant for Stem Cell Therapy The California Institute for Regenerative Medicine Mei-Yin Polley PhD, assistant Isaac Yang MD, chief resident in has awarded five California-based institutions adjunct professor of neurological the Department of Neurological $19,162,435 to advance stem cell based strategies surgery, was honored with the Award Surgery, was given the Kaiser for treating brain tumors. The objective of the grant for Excellence in Adult Clinical Resident Research Award at the is to file a new drug application with the U.S. Food Research at the 2009 joint meeting of 2009 meeting of the San Francisco and Drug Administration within four years, driving the Society for Neuro-Oncology and Neurological Society as well as the a stem cell-associated therapy towards clinical the AANS/CNS Section on Tumors Resident Research Award from the trial. The studies will be led by Mitchel Berger MD, for her paper entitled “Six-Month American Academy of Neurological chair of the UCSF Department of Neurological Progression-Free Survival as an and Orthopedic Surgeons. He has Surgery, and includes collaborators at the Ludwig Alternative Primary Efficacy Endpoint also earned a 2009 UCSF School of Institute for Cancer Research at UCSD, UCLA, to Overall Survival in Newly- Medicine Teaching Award. the Burnham Institute for Medical Research, and Diagnosed Glioblastoma Patients the Salk Institute. The overall goal of the project Receiving Temozolomide.” is to genetically engineer stem cells that home to and deliver therapeutic agents that specifically kill glioblastoma cells. The concept is based on the research team’s discovery that neural stem cells naturally seek out brain tumor cells. If the product of this research is approved by the FDA, it would be tested first in patients with recurrent glioblastoma. New Faculty are invited to submit cases for discussion to Judi Chesler at Clinical neuropsychologist Caroline Racine PhD has recently joined the Department, specializing in the assessment of cognition and Clinical Trial Highlights mood in patients with neurological • The Department of Neurological disorders. She serves as part of the Surgery has launched a phase II Caroline Racine PhD 7 multidisciplinary team for three main trial of the HSPPC-96 vaccine with patient groups: neuro-oncology, concurrent temozolomide in patients radiation oncology, and surgical with newly diagnosed glioblastoma movement disorders. Specifically, determine if extracranial-intracranial multiforme. Funded entirely through she provides neuropsychological (EC/IC) bypass surgery combined a Specialized Program of Research assessment for patients prior to with best medical therapy can reduce Excellence grant from the NCI and surgery or intervention (baseline subsequent ipsilateral ischemic patient advocacy groups, this will evaluations) and also provides stroke (fatal and non-fatal) at two be the first study of this brain tumor ongoing assessment in order to years by 40%, despite perioperative vaccine in patients with primary monitor cognitive function over time. stroke and death. Eligible participants tumors, after initial trials in recurrent The results of these evaluations must have internal carotid artery patients have demonstrated safety are used to assist with treatment occlusion producing hemispheric and a tumor-specific immune planning and return-to-work symptoms within the previous 120 response. By refining the patient strategies. Dr. Racine also takes a days and ipsilateral increased oxygen population and obtaining a better limited number of referrals to evaluate extraction fraction (OEF) measured understanding of the immune other individuals with cognitive by positron emission tomography response evoked during different complaint secondary to neurosurgical (PET). Clinically eligible subjects will stages of the cancer, we have the and/or neurological conditions. undergo PET. Those with increased potential to transform brain cancer OEF will be randomized equally to from a life-threatening illness into a undergo EC/IC bypass or not. Follow- New Skull Base Tumor Board chronic disease. Contact Andrew up is at one month and every three Parsa MD, PhD by e-mail at The Departments of Neurological months for two years. For those with Surgery and Otolaryngology – normal OEF, PET provides evidence Head and Neck Surgery are pleased • The UCSF Division of of good prognosis on medical to announce a new format for a Cerebrovascular Surgery is therapy alone. The study will pay for multidisciplinary skull base tumor participating in the Carotid PET and for EC/IC bypass surgery. board the first Thursday of each Occlusion Surgery Study (COSS), Contact Lisa Hannegan MS, CNS, month in L-34 in the Department an NIH-funded, randomized ACNP at (415) 476-2180 or by e-mail of Radiation Oncology. Physicians clinical trial. In this study, we will at
  8. 8. UCSF Department of Neurological Surgery 505 Parnassus Avenue, M779 Non-Profit Org U.S. Postage San Francisco, CA 94143-0112 PAID Permit 2310 Sacramento, CA selected recent publications from the department of neurological surgery Ahmed I, Auguste KI, Vachhrajani S, Dirks PB, Han YG, Kim HJ, Dlugosz AA, Ellison DW, Gilbertson RJ, Neurological Surgeons. Electrophysiological monitoring Drake JM, Rutka JT. Neurosurgical management of Alvarez-Buylla A. Dual and opposing roles of primary during surgery for cervical degenerative myelopathy and intracranial epidermoid tumors in children. J Neurosurg cilia in medulloblastoma development. Nat Med radiculopathy. J Neurosurg Spine 2009;11(2):245-252. Pediatr 2009;4(2):91-96. 2009;15(9):1062-1065. Sanchez-Mejia RO, McDermott MW, Tan J, Kim H, Baraban SC, Southwell DG, Estrada RC, Jones DL, Hashizume R, Ozawa T, Dinca EB, Banerjee A, Young WL, Lawton MT. Radiosurgery facilitates resection Sebe JY, Alfaro-Cervello C, García-Verdugo JM, Prados MD, James CD, Gupta N. A human brainstem of brain arteriovenous malformations and reduces Rubenstein JL, Alvarez-Buylla A. Reduction of seizures glioma xenograft model enabled for bioluminescence surgical morbidity. Neurosurgery 2009;64(2):231-240. by transplantation of cortical GABAergic interneuron imaging [published online ahead of print July 8, 2009]. Sorani MD, Lee M, Kim H, Meeker M, Manley GT. Race precursors into Kv1.1 mutant mice. Proc Natl Acad Sci J Neurooncol. doi: 10.1007/s11060-009-9954-9. ethnicity and outcome after traumatic brain injury at a USA 2009;106(36):15472-15477. Hetts SW, Narvid J, Sanai N, Lawton MT, Gupta single, diverse center. J Trauma 2009;67(1):75-80. Cernak I, Noble-Haeusslein LJ. Traumatic brain injury: N, Fullerton HJ, Dowd CF, Higashida RT, Halbach Starr PA, Martin AJ, Ostrem JL, Talke P, Levesque N, an overview of pathobiology with emphasis on military VV. Intracranial aneurysms in childhood: 27-year Larson PS. Subthalamic nucleus deep brain stimulator populations [published online ahead of print October single-institution experience. AJNR Am J Neuroradiol placement using high-field interventional magnetic 7, 2009]. J Cereb Blood Flow Metab. doi: 10.1038/ 2009;30(7):1315-1324. resonance imaging and a skull-mounted aiming device: jcbfm.2009.203. Jones DL, Baraban SC. Inhibitory inputs to hippocampal technique and application accuracy [published online Chang SM, Nelson S, Vandenberg S, Cha S, Prados M, interneurons are reorganized in Lis1 mutant mice. ahead of print August 14, 2009]. J Neurosurg. doi: Butowski N, McDermott M, Parsa AT, Aghi M, Clarke J Neurophysiol 2009;102(2):648-658. 10.3171/2009.6.JNS081161. J, Berger M. Integration of preoperative anatomic and McBride SM, Perez DA, Polley MY, Vandenberg SR, Shimamoto SA, Larson PS, Ostrem JL, Glass GA, metabolic physiologic imaging of newly diagnosed Smith JS, Zheng S, Lamborn KR, Wiencke JK, Chang Turner RS, Starr PA. Physiological identification of the glioma. J Neurooncol 2009;92(3):401-415. SM, Prados MD, Berger MS, Stokoe D, Haas-Kogan human pedunculopontine nucleus [published online Chou D, Acosta F, Cloyd JM, Ames CP. Parasagittal DA. Activation of PI3K/mTOR pathway occurs in most ahead of print October 14, 2009]. J Neurol Psychiatry. osteotomy for en bloc resection of multilevel cervical adult low-grade gliomas and predicts patient survival doi:10.1136/jnnp.2009.179069. chordomas. J Neurosurg Spine 2009;10(5):397-403. [published online ahead of print August 25, 2009]. Su X, Kells AP, Huang EJ, Lee HS, Hadaczek P, Beyer J, Christine CW, Starr PA, Larson PS, Eberling JL, Jagust J Neurooncol. doi: 10.1007/s11060-009-0004-4. Bringas J, Pivirotto P, Penticuff J, Eberling J, Federoff WJ, Hawkins RA, Vanbrocklin HF, Wright JF, Bankiewicz Nout YS, Mihai G, Tovar CA, Schmalbrock P, HJ, Forsayeth J, Bankiewicz K. Safety Evaluation of KS, Aminoff MJ. Safety and tolerability of putaminal Bresnahan JC, Beattie MS. Hypertonic saline attenuates AAV2-GDNF Gene Transfer into the Dopaminergic AADC gene therapy for Parkinson disease [printed cord swelling and edema in experimental spinal cord Nigrostriatal Pathway in Aged and Parkinsonian Rhesus online ahead of print October 21, 2009]. Neurology. injury: a study utilizing magnetic resonance imaging. Monkeys [published online ahead of print August 11, doi: 10.1212/WNL.0b013e3181c29356. Crit Care Med 2009;37(7):2160-2166. 2009]. Hum Gene Ther. doi:10.1089/hum.2009.103. Gonzalez-Perez O, Romero-Rodriguez R, Soriano- Panner A, Crane CA, Weng C, Feletti A, Wrensch M, Jenkins RB, Chang JS, Yeh RF, Xiao Y, Navarro M, Garcia-Verdugo JM, Alvarez-Buylla A. Parsa AT, Pieper RO. A novel PTEN-dependent link Decker PA, Ballman KV, Berger M, Buckner JC, Epidermal growth factor induces the progeny of to ubiquitination controls FLIPS stability and TRAIL Chang S, Giannini C, Halder C, Kollmeyer TM, Kosel subventricular zone type B cells to migrate and sensitivity in glioblastoma multiforme. Cancer Res ML, LaChance DH, McCoy L, O’Neill BP, Patoka J, differentiate into oligodendrocytes. Stem Cells 2009;69(20):7911-7916. Pico AR, Prados M, Quesenberry C, Rice T, Rynearson 2009;27(8):2032-2043. Resnick DK, Anderson PA, Kaiser MG, Groff MW, AL, Smirnov I, Tihan T, Wiemels J, Yang P, Wiencke Heary RF, Holly LT, Mummaneni PV, Ryken TC, Choudhri JK. Variants in the CDKN2B and RTEL1 regions are Editor: Ilona Garner ( TF, Vresilovic EJ, Matz PG; Joint Section on Disorders associated with high-grade glioma susceptibility. of the Spine and Peripheral Nerves of the American Nat Genet 2009;41(8):905-908. 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