USC Department of Neurological Surgery 2020 - 2021 Annual Report Keck School of Medicine of USC 02-03 Chairman's Message 04-07 Training and Education 08-19 Comprehensive Stroke and Cerebrovascular Center 20-29 Deep Brain Stimulation Center 30-41 Pediatric Neurosurgery Program 42-49 Minimally Invasive Neurosurgery and Endoscopic Skull Base/Pituitary Center 50-55 NeuroTrauma and NeuroCritical Care 56-69 Spine Center 70-75 Radiosurgery Center 76-85 Neuro-Oncology 86-95 USC Epilepsy Care Consortium FROM THE CHAIRMAN The 2020-21 era was a momentous time for the the most malignant of brain tumors. Dr. Charles Liu, Department of Neurosurgery at the Keck School of Director of our NeuroRestoration Center, and Dr. Jon Medicine of USC. We added three new clinician scientists Russin published a paper in Nature BME on the first in- who are already prestigious faculty. All have contributed human functional brain imaging using photo acoustic to both our patient care model as well as our research computed tomography. This work was recognized with and academic productivity model. Ashkan Mowla, MD, the best paper award by the Society of PhotoOptical who was an accomplished stroke neurologist, comes to Instrumentation Engineers. us through his neurointerventional fellowship at UCLA. He is now a member of our Cerebrovascular Disorders In conjunction with the USC Cardiac and Vascular Division and practices at our Comprehensive Stroke Institute and the USC Division of Plastic and Center at the Hospital of the Good Samaritan. David Reconstructive Surgery, Dr. Jon Russin has pioneered Cheng, MD, who is trained as a Physical Medicine and a novel technique for spinal cord revascularization Rehabilitation professional, comes to us from Rush to prevent paralysis when treating complex aortic School of Medicine. David has assumed the role of our aneurysms. expert in non-surgical management of spinal disorders. David has taken on the additional responsibility of Dr. Darrin Lee is a Principal Investigator in the Advance teaching several classes within the Keck School of II Trial and was the first in California to implant a deep Medicine. Frances Chow, MD returns to Keck, having brain stimulator for Alzheimer’s Disease. completed her neurology residency at USC, followed by a prestigious fellowship at UCLA in neuro-oncology. With And finally, in a widely touted study that made national the advent of Dr. Chow’s arrival we were able to make a media, our NeuroRestoration Center has demonstrated major University-wide announcement on the inauguration the beneficial effect of adding neuromodulation to task of the USC Brain Tumor Center. There will be more about specific therapy in chronic stroke patients, even 10 that to come, but Dr. Chow is a major contributor to our years after the stroke. Appearing in the April edition of Center concept. The Lancet, the paper published with an accompanying editorial. The residency training program continues to gain national accolades. By most objective criteria it resides in the top The Department of Neurosurgery remains on the cutting 20 of the 115 residency training programs in neurological edge of clinical neuroscience research and continues surgery across the country. If one looks at the number its legacy in training future leaders of American of full-time academic surgeons that are graduates of Neurosurgery. our program and further looks at the fact that seven Department Chairs across the country have trained in Sincerely yours, our program we are closer to the top five in the nation.

Since going to press with our Annual Report, a number of research accomplishments have been announced. Steven L. Giannotta, MD Dr. Frank Attenello’s lab has been able to identify tumor Professor and Chairman and stem cell genes that can be utilized for treating Program Director

Fiber tracking of the hippocampal sub-regions using 16.4 Tesla MRI. Credit: Kristi Clark, PhD, Carol Miller, PhD, Charles Liu, MD, PhD, and Jonathan Russin, MD. Keck School of Medicine of USC 03 steven john gabriel Training and Education GIANNOTTA, MD LIU, MD ZADA, MD, MS

f the approximately 64 residency training prestigious universities to apply to our training program. We programs at LAC+USC Medical Center, the are proud of the fact that a relatively high proportion (greater Neurosurgical Residency program is one of the than 50%) of our residents seek full-time academic jobs most elite. The program was inaugurated in upon completion of their training. Our resident graduates 1927 by Carl Rand, and as such, was the first have assumed positions in such prestigious programs as neurosurgical residency training program west Barrow Neurological Institute, Columbia, Yale, UCLA and USC. of the Mississippi. Currently four graduates of our training program are Chairmen of academic neurosurgical departments including University of OThe quality of our program was recently acknowledged by the Utah, University of Texas at Austin, University of Arkansas, and Neurosurgery Residency Review Committee, which allowed us to University of Missouri. increase our enrollment to three residents per year. The factors governing such a decision include the quality of the faculty, the This past academic year alone our residents have authored, excellence of the care given, the success of the residents who or co-authored, over 80 peer-reviewed publications and book graduate from the program, and the quality of the research chapters. Whether our graduates choose a career in academic efforts within the Department. medicine or private practice, they tend to ascend to leadership roles, whether it be locally at their hospitals, or nationally in As a relatively large department (24 clinical and 7 research organizations such as the Congress of Neurological Surgeons, faculty) we not only provide excellence in subspecialty the North American Spine Society or the Council of State neurosurgical care but also provide an environment of cutting Neurosurgical Societies. edge research. This attracts medical students from our most

04 05 TRAINING and EDUCATION 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery keck.usc.edu/neurological-surgery/ Clinic (323) 442-5720 Academic Office (323) 409-7422 Keck School of Medicine of USC USC Department of Neurological Surgery Residents 2021-2022 POST GRADUATE POST GRADUATE POST GRADUATE POST GRADUATE POST GRADUATE POST GRADUATE POSTPOST GRADUATEGRADUATE YEAR 1 YEAR 2 YEAR 3 YEAR 4 YEAR 5 YEAR 6 YEARYEAR 77

PGY-3 CHLA, KECK HOSPITAL, AND LAC+USC PEDIATRIC, PGY-4 KECK HOSPITAL AND LAC+USC PGY-5 CHIEF, KECK HOSPITAL OF USC AND PGY-6 RESEARCH/CLINICAL PGY-7 RESIDENT SUPERVISORS PGY-1 INTERN YEAR PGY-2 LAC+USC MEDICAL CENTER, ENDOVASCULAR, AND CRANIAL NEUROSURGERY SPINAL NEUROSURGERY STEREOTACTIC RADIOSURGERY ELECTIVE YEAR BASIC CLINICAL NEUROSURGERY Josh Bakhsheshian, MD, MS Undergraduate: UC San Diego- BS, Physiology and Neuroscience Alexandra Kammen, MD hillip onney David Cote, MD Jonathan Dallas, MD Robert Briggs, MD Jonathon Cavaleri, MD P B , MD Medical School: Chicago Medical School, Rosalind Franklin University of Medicine and Science Undergraduate Education: University of Undergraduate Education: Oklahoma State Undergraduate Education: University of Tulsa- BS Undergraduate Education: Boston College – BS Undergraduate Education: Washington Undergraduate Education: College of William California Berkeley - BA Molecular and Graduate School: College of Health Professions, Rosalind Franklin University of University – BS Chemical Engineering Petroleum Engineering Chemistry, Theology University – BS Biomedical Engineering and Mary – BS Chemistry, Neuroscience Cell Biology Medicine and Science- MS, Healthcare Administration and Management; MS, edical chool ducation Medical School Education: Harvard Medical edical chool ducation Medical School Education: University of edical chool ducation M S E : University of Biomedical Sciences M S E : Vanderbilt University M S E : Icahn School of Medical School Education: Keck School of Oklahoma College of Medicine Oklahoma College of Medicine School School of Medicine Medicine at Mount Sinai Medicine of USC Ki Chang, MD lexander hartrain Tats Fujii, MD Raghav Gupta, MD Michelle Lin, MD A C , MD Undergraduate Education: Hope College (Holland, MI) - BA Chemistry and Angad Gogia, MD Shivani Rangwala, MD Undergraduate Education: Middlebury College- BA Undergraduate Education: The College of New Undergraduate Education: Washington Undergraduate Education: University of Undergraduate Education: Stanford University – Undergraduate Education: Washington Neuroscience Psychology Jersey – BS Biology University in St. Louis - BA Philosophy, Colorado – BA, Biochemistry and Molecular, BS Computer Science University – BS, Biomedical Engineering Medical School Education: Keck School of Medical School Education: Penn State College of Medicine Medical School Education: Rutgers New Jersey Neuroscience, Psychology Cellular and Developmental Biology Medical School Education: Keck School of Medical School Education: University of Illinois Medicine of USC Medical School Medical School Education: Keck School of Medical School Education: University of Medicine of USC College of Medicine Medicine of USC Pittsburgh School of Medicine

Saman Sizdahkhani, MD, MS Anadjeet Khahera, MD Justin Lee, MD, PhD Ben Strickland, MD ames u Lawrance Chung, MD Undergraduate Education: McGill University – BS, Keiko Kang, MD J Y , MD Undergraduate Education: Georgetown Undergraduate Education: University of ndergraduate ducation Neuroscience Undergraduate Education: Clemson University, Clemson, SC - BA Biological Undergraduate Education: University of Undergraduate Education: Vanderbilt U E : University of California Los Angeles – BS, Integrative University-, BS Biology Sciences, BA Economics Southern California – BS Biochemistry University – BA Economics, Spanish California Los Angeles – BS, Biology Medical School Education: Chicago Medical School at Biology & Physiology Rosalind Franklin University of Medicine & Science Medical School Education: Columbia University edical chool ducation Medical School Education: University of Minor: Chemistry M S E : University of College of Physicians and Surgeons Medical School Education: Baylor College of Medicine Medical School Education: University of Graduate Education: College of Health Professions at California San Diego Medical School Education: Brown University California Los Angeles David Geffen Graduate School: Columbia University- PhD California Irvine College of Medicine Rosalind Franklin University of Medicine & Science School of Medicine – MS, Biomedical Sciences Neurobiology and Behavior

The intern year includes neurosurgery, neurocritical The PGY-2 year is spent primarily on the service During the PGY-3 year, the resident has several During the PGY-4 year additional focused rotations Residents spend the entire PGY-5 year at Keck Hospital The PGY-6 year of residency is spent exclusively As a PGY-7, the resident is promoted to a position of Resident Supervisor, which entails the care, neuroradiology, and other surgical rotations. at the LAC+USC Medical Center with two months spent focused rotations: continue with increasing levels of responsibility. of USC with rotations focused on Complex Cranial Neuro- pursuing a focused area of interest either clinically or following: at Keck Hospital. The year focuses on basic clinical surgery and Complex Spinal Neurosurgery, as chiefs of with research. • Pediatric Neurosurgery at the Childrens Hospital of • Stereotactic Radiosurgery/Research: This rotation • Assumes primary responsibility of the day to day operation of one of the two services at neurosurgery skills. These skills include: the services. It is supplemented by a block of dedicated Los Angeles: It is expected that the resident will provides a complete radiosurgery experience and the LAC+USC Medical Center. research. This year provides the individual with an opportunity to • Become expert in the performance of the become familiar with those disorders that occur with provides time for residents to continue or develop avail themselves of the facilities of the entire University • All of the administrative needs of these services are provided by the resident supervisor, neurological examination in both elective and greatest frequency in the pediatric population and the basic science, clinical research, or outcomes projects, • Cranial Service: The resident is an active operative part- community providing the resources of a major research who has the authority to assign operative cases at all levels. emergency situations. surgical techniques applied to their correction especially as they prepare for dedicated focus during icipant in the full spectrum of cases on the services university that ranks amongst the ten leading research- including neonatal populations and mastering PGY-6. with the expectation that the resident will acquire a • This year provides a broad opportunity to finely tune one’s operative skills and provide • Become fully cognizant of the measures necessary funded universities in the United States. performance of shunting procedures for broad exposure to microsurgical techniques in the oversight for the entire management of the patient population on the service utilizing the to stabilize the acutely ill neurosurgical patient and • Cranial Service at Keck Hospital of USC: Residents hydrocephalus. adult patient. He/she will subsequently understand the consultative opportunities provided by the attending staff. the need to render emergent neurosurgical are involved in intracranial neurosurgery cases as This year can also be used to pursue an infolded principles of microsurgery along with the technical treatment when necessary. • Endovascular Neurosurgery at Keck Hospital of USC well as participating in faculty clinics. fellowship in a particular area of clinical interest. aspects of utilization of the opera-tive microscope and • Upon completion on this experience, it is anticipated that the individual will be able to and LAC+USC Medical Center: This rotation focuses manage the full spectrum of neurosurgical disease and to understand the mechanisms of • Mastering the full pre and postoperative evaluation • At LAC+USC Medical Center, residents gain a large other surgical technologies. on interventions for stroke and cerebrovascular and needs for supervision at every level of resident education. and treatment of neurosurgical patients. experience in treating traumatic spine injuries as the disorders and diagnostic angiograms. • Spine Service: The resident gains a full understanding of senior resident for the combined spine service. • The individual will be fully prepared to assume total care of any patient with any • Acquiring operative skills on cases that range from complex spinal neurosurgery including instrumentation • Spinal Neurosurgery at Keck Hospital of USC: As neurosurgical problem and to establish the foundation of a career in either academic or traumatic head and spinal injury to complex and tumor. the junior resident on the spine service an emphasis is community based practice. elective cases. placed on a comprehensive experience including • As Chief Resident on each service, under supervision pre and post-op care, outpatient clinic with faculty, of the attending staff, the resident is responsible for and operative experience. the assignment of residents to specific surgical cases, in addition to providing general administrative assignments for day to day operation. The cranial chief also adminis- trates the call schedule. • Research: Residents continue basic science, clinical research, or outcomes projects, especially as they prepare for dedicated focus during PGY-6.

06 TRAINING and EDUCATION 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery keck.usc.edu/neurological-surgery/ Clinic (323) 442-5720 Academic Office (323) 409-7422 Keck School of Medicine of USC 07 CONDITIONS WE TREAT and FY 2020 Procedures TREATMENTS WE PROVIDE Adult cerebrovascular cases performed at Keck Medical Center of USC, LAC+USC Medical Center, and Good Samaritan Hospital. ARTERIOVENOUS MALFORMATIONS Treatment: Microsurgical Resection, steven arun william jonathan matthew 365 GIANNOTTA, MD AMAR, MD MACK, MD RUSSIN, MD TENSER, MD Endovascular Embolization, Radiosurgery Diagnostic Angiogram USC Comprehensive Stroke and Procedures CAROTID STENOSIS Cerebrovascular Center Treatment: Carotid Endarterectomy, 87 Angioplasty and Stent Vasospasm Treatment Procedures ashkan parham MOWLA, MD YASHAR, MD CAVERNOUS MALFORMATIONS Treatment: Microsurgical Resection 77 he USC Comprehensive Stroke and Cerebrovascular treatment in the emergency department and then transfer the patient Cerebral Aneurysm CEREBRAL ANEURYSMS Clipping Procedures Center provides a wide range of services, using the latest to a specialty center for a higher level of care. The Keck Hospital of Treatment: Flow Diversion Embolization, medical, surgical, and interventional techniques, covering all USC provides community hospitals with a tertiary/quaternary transfer Microsurgical Clipping, Endovascular aspects of stroke. The multi-disciplinary team meets option via our Rapid Transport Program for patients Coiling 109 Cerebral Aneurysm the needs of patients with acute stroke and presenting with acute stroke. Upon arrival at our Embolization Procedures other serious neurological and neurosurgical hospital, the patient is rapidly admitted to our INTRACRANIAL ATHEROSCLEROSIS Treatment: Endovascular Stenting, conditions by providing immediate, advanced neurocritical care unit dedicated to patients with Surgical Revascularization

treatment and neurocritical care. More than severe brain or spine injuries where they can 31 Arteriovenous Malformation 2600 stroke related visits occur per year receive cutting edge multi-disciplinary care, ISCHEMIC STROKE Procedures in the Keck Hospital of USC and the advanced imaging, specialized procedures Treatment: Thrombolysis, IV tPA, Intra-Arterial Thrombectomy, Leslie P. Weiner Neurological Care and and surgeries as needed. The collaboration Angioplasty, Stenting 113 Research Center, with an even larger number between stroke neurologists, neurointensivists, Mechanical Thrombectomy for Acute Stroke Procedures occurring in the Los Angeles County system. neurosurgeons, interventional radiologists, MOYA MOYA DISEASE neuroradiologists and vascular surgeons, allows Treatment: Surgical Revascularization, Illustration of a proposed treatment paradigm for The Keck Medical Center of USC offers a highly anterior spinal artery preservation based on its us to offer unique treatment options to our EC-IC Bypass 30 proximity to fusiform vertebral artery aneurysms. Cerebral Bypass specialized level of care and treatment for stroke Credit: Jonathan Russin, MD. patients, including; endovascular procedures to Revascularization Procedures and other cerebrovascular disorders that is open a blocked artery, surgery to repair a source unavailable in many community hospitals. Frequently, community of bleeding or to bypass a blockage, and exceptional neurocritical care 20 hospitals and primary stroke centers will offer immediate, brain-saving to prevent and manage life-threatening complications. Carotid Angioplasty and Stenting and Carotid Endarterectomy Revascularization Procedures

08 CEREBROVASCULAR 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery keck.usc.edu/neurological-surgery/ Clinic (323) 442-5720 Academic Office (323) 409-7422 Keck School of Medicine of USC 09 Intraoperative photograph of a trapped fusiform The Cerebrovascular Center, headed by Steven Giannotta, MD, leads the nation in experience with operative aneurysm after completion of arborization bypass. The side-to-side bypass’ are identified by black and white management of aneurysms and arteriovenous malformations. Our team also treats carotid stenosis, cavernous arrows. Credit: Jonathan Russin, M.D. malformations, stroke/transient ischemic attack, hemifacial spasm, and trigeminal neuralgia.

CEREBROVASCULAR

he cerebrovascular team at USC cerebral revascularization/ bypass procedures, and were previously routed to other centers within its is comprised of neurosurgeons, resection of cavernous malformations. catchment area. As a result, its stroke volume has neurologists and radiologists. They risen exponentially, and LAC+USC is currently one have worked closely with the Stroke Dr. Arun Amar is the Director of Endovascular of the busiest stroke programs in the county. This and Neurocritical care team to develop a Neurosurgery at USC and also serves as the robust experience provides the foundation for future robust transfer program for emergent and Stroke Director and Chief of Neurosurgery at certification as a Comprehensive Stroke Center. complexT neurovascular care. The endovascular and the LAC+USC Medical Center. This is the only open cerebrovascular teams perform procedures Los Angeles Department of Health Services (DHS) Dr. William Mack is Professor of Neurosurgery at Keck Hospital, LA County Hospital, and Good facility that is certified as a Primary Stroke Center (Clinical Scholar) and the Vice Chair of Samarian Hospital. (PSC) by the Joint Commission, the nation’s oldest Academic Affairs in the Department of and largest standards-setting and accrediting Neurosurgery. He was inducted into the Society From July 2018- June 2019 more than 360 diagnostic body in healthcare, and is one of the rare PSCs at a of Neurological Surgeons (SNS) and named a angiograms and more than 380 therapeutic government-funded facility. This designation was Fellow of the American College of Surgeons (FACS). endovascular procedures were performed. More earned in Nov 2016 in recognition of the breadth He was elected Vice President of the Society of than 125 open vascular cases were performed and quality of care LAC+USC provides to stroke Neurointerventional Surgery (SNIS) and a Member- including aneurysm clipping/trapping, arteriovenous patients. PSC designation entitled LAC+USC to at-Large on the executive committee of the malformation resections, carotid endarterectomies, receive ambulance traffic of stroke patients who American Association of Neurological Surgeons

10 CEREBROVASCULAR 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery keck.usc.edu/neurological-surgery/ Clinic (323) 442-5720 Academic Office (323) 409-7422 Keck School of Medicine of USC 11 (AANS)/Congress of Neurological Surgeons (CNS) lectures for non-physicians regarding treatment of USC in 2014. The unique nature of our Cerebral Cerebrovascular Section. He is an Associate Editor acute stroke and stroke prevention. Dr. Tenser has Revascularization program sets USC apart from other of the Journal of Neurointerventional Surgery been involved in professional societies, serving as a academic centers and seeks to provide patients with and a member of the Editorial Board of World moderator for the International Stroke Conference treatment options that allow them to return to their Neurosurgery. and SNIS meeting and as an instructor for the SNIS/ normal lives. Cerebrovascular Section Fellow’s Course. Dr. Matthew Tenser has been active in The annual USC Cerebrovascular Symposium, establishing one of the busiest Comprehensive Dr. Jonathan Russin is the Director and directed by Dr. Arun Amar, was held on October Stroke programs in Los Angeles at Good founder of the USC Cerebral Revascularization 13, 2018. The conference was a great success with 16 Samaritan Hospital. The Good Samaritan Hospital Center and Chair of the Joint AANS/CNS USC and guest faculty speakers and more than 150 Stroke Program continues to grow, averaging 80-90 Cerebrovascular Section Website Committee. participants in attendance. Topics covered included stroke codes per month (up 10-20 per month from Under his direction, the open cerebrovascular expanding the role of mechanical thrombectomy, last year). Last year at Good Samaritan Hospital, surgical division has pioneered new interventions such as in patients with symptoms longer than 8 we gave the most IV tPA in Southern California, and for the most complex pathologies. These hours or with large core infarcts, as well as the were the second busiest thrombectomy center (78 accomplishments include the intraoperative resurrection of stenting for intracranial stenosis, mechanical thrombectomy procedures). We recently analysis of cerebral blood flow to predict and flow diversion for ruptured aneurysms, innovations earned several awards from the American Heart prevent postoperative strokes, new treatments to in cerebrovascular bypass, and updates from the Association - the 2019 Get With The Guidelines - prevent vasospasm after bypass surgery, alternative International Stroke Conference. Novel management Stroke Gold Plus Award, as well as Target: Stroke bypass graft selections and novel suturing and treatment paradigms were discussed from a Elite Plus Honor Roll recognition, both signifying techniques to maximize efficiency. The USC Cerebral stroke neurology, neurocritical care, and surgical/ their highest possible level of achievement and Revascularization Center is a unique collaboration endovascular perspective. Dr. Amar delivered the recognition in stroke care. between neurosurgery and plastic surgery that has keynote address about the challenges of building facilitated the expansion of microsurgical treatments the stroke center of the future. Dr. Tenser lectured at Dr. Tenser has given CME lectures for physicians for complex cerebrovascular patients. Our team has the Stroke Symposium at Good Samaritan Hospital. regarding the medical and endovascular care of managed over 150 complex bypass procedures since Dr. Amar spoke about advanced imaging for triaging patients with cerebrovascular disease. He is also its inception and Dr. Russin has performed over stroke patients at the Adventist Health annual active in community education and frequently gives 500 open cerebrovascular surgeries since joining Cardio-Cerebral symposium. Matthew Tenser, MD, William Mack, MD, and Arun Amar, MD (left), and imaging demonstrating complete occlusion in a patient with an aneurysm and subarachnoid hemorrhage (right). Credit: William Mack, MD.

12 CEREBROVASCULAR 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery keck.usc.edu/neurological-surgery/ Clinic (323) 442-5720 Academic Office (323) 409-7422 Keck School of Medicine of USC 13 Intraoperative Indocyanine Green-based flow analyses. CEREBROVASCULAR RESEARCH The analyses provide a real-time, semiquantitative measure of intraoperative cortical perfusion during r. Mack is a faculty member of the Neurosurgery Resident Research Education Program. NINDS R25 awards and was recently invited to serve cerebral bypass surgery for complex aneurysms. Credit: Jonathan Russin, MD. Neuroscience Graduate Program, and This has helped promote a strong academic on the NINDS study section for clinician scientist the Director of the Cerebrovascular culture and develop a dedicated cohort of clinician mentored training grants (K02, K23, K08). Laboratory at the Zilkha Neurogenetic scientists among our trainees. Dr. Mack serves as a Institute. Dr. Mack’s laboratory is mentor on two NIH KL2 career development awards Dr. Mack helps lead a productive USC focused on translational efforts to treat for Assistant Professors in the USC Department of Multidisciplinary Neuroscience Outcomes Research Dstroke and cerebrovascular disease. The group Group that studies outcomes using large datasets. employs experimental models of stroke and chronic The team is comprised of faculty members from the cerebral hypoperfusion (decreased blood flow to Neurosurgery, Neurology, and Preventive Medicine the brain) to assess environmental exposures and departments in addition to multiple fellows, evaluate novel therapeutic agents. Current studies residents and medical students. To date the team are focused on the impact of nanoparticulate matter has published over forty peer-reviewed manuscripts from vehicular exhaust (air pollution), a potent in a broad range of scientific journals including source of inflammation and oxidative stress. Dr. BMJ, Evidence Based Medicine, and Journal of Mack employs a refined model of carotid stenosis Neurosurgery. Dr. Mack is the site PI on the Coast to demonstrate the impact of air pollution on white (Coiling of aneurysms smaller than 5mm with matter ischemic injury and neurocognitive deficits in hypersoft) registry. the setting of underlying cerebrovascular disease.

Pericyte response (coverage was decreased and blood brain As Director of the Cerebral Revascularization Dr. Mack has an R01 award through the NIH/NIEHS barrier permeability increased) following experimental Center and Associate Director of the USC bilateral carotid artery stenosis. Sections obtained from the ONES (Outstanding New Environmental Scientist) medial portion of the corpus callosum (top). Pericyte and Neurorestoration Center, Dr. Russin has been and is the Project lead on a P01 award through the vascular staining at days 1, 3, 7, and 30 (bottom). Credit: focused on creating novel solutions to clinical William Mack, MD. NIH/ NIA. Dr. Mack’s team has published recent problems that are able to immediately impact articles in the Journal of Cerebral Blood Flow and Neurosurgery and on the National Advisory Council patient care. His research efforts have recently Metabolism and Nature Medicine. Dr. Mack is the of the Neurosurgery NINDS K12 training grant. He resulted in him being awarded an RO3 through the Principal Investigator on the NIH/ NINDS R25 USC serves on the NIH study section/ review panel for NIH/NINDS to continue his investigations into

14 CEREBROVASCULAR 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery keck.usc.edu/neurological-surgery/ Clinic (323) 442-5720 Academic Office (323) 409-7422 Keck School of Medicine of USC 15 SELECTED PUBLICATIONS

Montagne A, Ravina K, Strick- Russin JJ, Montagne Rennert RC, Strickland the mechanisms of botulinum toxin when used safety of endovascular thrombectomy compared Nikolakopoulou AM, land BA, Rennert A, D’Amore F, He S, BA, Ravina K, Brandel to prevent vasospasm after bypass surgery. The to medical management alone in acute ischemic Zhao Z, Sagare AP, Si RC, Fredrickson VL, Shiroishi MS, Rennert MG, Bakhsheshian G, Lazic D, Barnes SR, Bakhsheshian J, Chien RC, Depetris J, J, Fredrickson VL, Revascularization Center is also working with the stroke patients due to a large vessel occlusion in Daianu M, Ramanathan M, Mack WJ, Amar Zlokovic BV, Mack Carey J, Russin German manufacturer of optical systems and the distal ICA and MCA M1 who have large core A, Go A, Lawson AP, Russin JJ. Fusi- WJ. Permeability JJ. Assessment EJ, Wang Y, Mack form vertebral artery imaging as a of ischemic risk optoelectronics, Zeiss, to improve patient safety on either CT or advanced perfusion imaging on WJ, Thompson PM, aneurysms involving predictor of delayed following intracranial- by better understanding intraoperative changes CTP or both and are treated within 0-24 hours Schneider JA, Varkey the posterior inferior cerebral ischemia to-intracranial and J, Langen R, Mullins cerebellar artery after aneurysmal extracranial-to- in cerebral blood flow after bypass surgery. In the from last known well time. Additionally, we will E, Jacobs RE, Zlokovic origin associated with subarachnoid intracranial bypass BV. Pericyte degeneration causes white matter the sole angiographic anterior spinal artery hemorrhage. J Cereb Blood Flow Metab. 2018 for complex aneurysms using intraoperative past year Dr. Russin and his team have contributed be participating in the Pre-Hospital Administration dysfunction in the mouse central nervous origin: technical case report and treatment par- Jun;38(6):973-979. doi: 10.1177/0271678X18768670. Indocyanine Green-based flow analysis. 30 publications to the peer-reviewed literature on of Stroke Therapy - Trans Sodium Crocetinate system. Nat Med. 2018 Mar;24(3):326-337. adigm proposal. J Neurosurg. 2018 Oct 1:1-7. J Clin Neurosci. 2019 Sep;67:191-197. cerebrovascular disease and he was recently asked (PHAST-TSC) Trial, which will examine if TSC is a Babadjouni R, Patel A, Liu Q, Shkirkova K, Lamorie-Foote K, Connor M, Hodis Liu Q, Radwanski R, Babadjouni R, Patel A, Hodis DM, Baumbacher P, Zhao Shao X, Zhao Z, Russin JJ, Amar AP, Sanossian N, Wang DJ, Yan L. to guest edit a JNS Focus issue on bypass surgery. neuroprotectant when given to stroke patients within DM, Cheng H, Sioutas C, Morgan TE, Finch CE, Mack WJ. Nanoparticulate Z, Zlokovic B, Mack WJ. Experimental chronic cerebral hypoperfusion Quantification of intracranial arterial blood flow using noncontrast This team represents a youthful and energetic the first 2 hours of stroke. The trial will be performed matter exposure results in neuroinflammatory changes in the corpus results in decreased pericyte coverage and increased blood-brain enhanced 4D dynamic MR angiography. Magn Reson Med. 2019 callosum. PLoS One. 2018 Nov 5;13(11):e0206934. barrier permeability in the corpus callosum. J Cereb Blood Flow Metab. Jul;82(1):449-459. center for innovative research that is rapidly with both primary and comprehensive stroke centers 2019 Feb;39(2):240-250. Bonney PA, Walcott BP, Singh P, Nguyen PL, Sanossian N, Mack WJ. Shkirkova K, Connor M, Lamorie-Foote K, Patel A, Liu Q, Ding L, garnering a national reputation for excellence in in LA county, as well as paramedics from the LA The Continued Role and Value of Imaging for Acute Ischemic Stroke. Rangwala SD, Strickland BA, Rennert RC, Ravina K, Bakhsheshian J, Amar AP, Sanossian N, Attenello FJ, Mack WJ. Frequency, Neurosurgery. 2019 Jul 1;85(suppl_1):S23-S30. Hurth K, Giannotta SL, Russin JJ. Ruptured Mycotic Aneurysm of predictors, and outcomes of readmission to index versus its contributions to clinical care and academic County EMS devices in the same way FAST MAG. the Distal Circulation in a Patient with Mucormycosis Without Direct non-index hospitals after mechanical thrombectomy in discovery. Buchanan IA, Lin M, Donoho DA, Patel A, Ding L, Amar AP, Giannotta Skull Base Extension: Case Report. Oper Neurosurg. 2019 Mar patients with ischemic stroke. J Neurointerv Surg. 2019 Jul 26. SL, Mack WJ, Attenello F. Predictors of Venous Thromboembolism 1;16(3):E101-E107. pii: neurintsurg-2019-015085. Members of our cerebrovascular team have been After Nonemergent Craniotomy: A Nationwide Readmission Database Analysis. World Neurosurg. 2019 Feb;122:e1102-e1110. Ravina K, Rennert RC, Strickland BA, Chien M, Carey JN, Russin JJ. Strickland BA, Bakhsheshian J, Rennert RC, Fredrickson VL, Dr. Russin and Mack were supported by a grant on the steering committees of multiple landmark Pedicled temporoparietal fascial flap for combined revascularization in Lam J, Amar AP, Mack WJ, Carey J, Russin JJ. Descending Branch from the Brain Aneurysm Foundation to utilize data clinical trials resulting in the approval of stroke Dominguez R, Zitting M, Liu Q, Patel A, Babadjouni R, Hodis DM, Chow adult moyamoya disease. J Neurosurg. 2018 Nov 1:1-7. of the Lateral Circumflex Femoral Artery Graft for Posterior Inferior RH, Mack WJ. Estradiol Protects White Matter of Male C57BL6J Mice Cerebellar Artery Revascularization. Oper Neurosurg. 2018 Sep 1;15(3): obtained from advanced MRI perfusion imaging devices for mechanical thrombectomy. Dr. Amar has against Experimental Chronic Cerebral Hypoperfusion. Ravina K, Strickland BA, Rennert RC, Bakhsheshian J, Russin 285-291. J Stroke Cerebrovasc Dis. 2018 Jul;27(7):1743-1751. JJ, Giannotta SL. Revision Microvascular Decompression for sequences to assess for an association between served as chairman or member of the Clinical Events Trigeminal Neuralgia and Hemifacial Spasm: Factors Strickland BA, Rennert RC, Bakhsheshian J, Ravina K, Fredrickson blood brain barrier breakdown following aneurysm CT perfusion imaging demonstrating increased mean transit Committee for several multicenter cerebrovascular Rennert RC, Strickland BA, Ravina K, Bakhsheshian J, Fredrickson Associated with Surgical Failure. J Neurol Surg B Skull Base. 2019 VL, Giannotta SL, Russin JJ. Extracranial-Intracranial Bypass for time and decreased cerebral blood flow within the right middle VL, Tenser M, Amar AP, Mack WJ, Carey J, Russin JJJ. Efficacy and Feb;80(1):31-39. Treatment of Blister Aneurysms: Efficacy and Analysis of rupture and cerebral vasospasm. The study, cerebral territory. Credit: Jonathan Russin, MD. trials, including SWIFT PRIME, PREMIER, APOLLO, Outcomes of Posterior Inferior Cerebellar Artery (PICA) Bypass for Complications Compared with Alternative Treatment Strategies. Proximal PICA and Vertebral Artery-PICA Aneurysms: A Case Series. Ravina K, Strickland BA, Rennert RC, Chien M, Mack WJ, Amar AP, World Neurosurg. 2018 Sep;117:e417-e424. published in the Journal of Cerebral Blood Flow and PFLEX, and STRATIS, leading to FDA approval of tools Oper Neurosurg. 2018 Oct 1;15(4):395-403. Russin JJ. A3-A3 Anastomosis in the Management of Complex Anterior Metabolism, demonstrated that global MR derived Bee Foundation to study the effect of Minocycline such as the Solitaire stent retriever and Pipeline Cerebral Artery Aneurysms: Experience With in Situ Bypass and Tang AM, Bakhsheshian J, Ding L, Jarvis CA, Yuan E, Strickland Donoho DA, Patel A, Buchanan IA, Chow F, Ding L, Amar AP, Attenello Lessons Learned From Pseudoaneurysm Cases. Oper Neurosurg. 2019 BA, Giannotta SL, Amar AP, Attenello FJ, Mack WJ. Nonindex Blood Brain Barrier permeability is higher during on Blood Brain Barrier permeability following embolization device. He was also site PI on the F, Mack WJ. Treatment at Safety-Net Hospitals Is Associated with Sep 1;17(3):247-260. Readmission After Ruptured Brain Aneurysm Treatment Is Delays in Coil Embolization in Patients with Subarachnoid Hemorrhage. Associated with Higher Morbidity and Repeat Readmission. the vasospasm risk period (post bleed day 4) in aneurysmal subarachnoid hemorrhage. Intraventricular Nimodipine for preventing cerebral World Neurosurg. 2018 Dec;120:e434-e439. Rennert RC, Strickland BA, Ravina K, Bakhsheshian J, Fredrickson VL, World Neurosurg. 2019 Oct;130:e753-e759. patients that subsequently develop delayed cerebral vasospasm following subarachnoid hemorrhage trial Carey J, Russin JJ. Intraoperative Assessment of Cortical Perfusion Fredrickson VL, Strickland BA, Ravina K, Rennert RC, Donoho DA, After Intracranial-To-Intracranial and Extracranial-To-Intracranial Zaidat OO, Castonguay AC, Rai AT, Badruddin A, Mack WJ, Alshekhlee ischemia. The team (along with Chief Resident Ben Dr. Tenser is the site interventional PI on the that concluded in 2018. Buchanan IA, Russin JJ, Mack WJ, Giannotta SL. State of the Union in Bypass for Complex Cerebral Aneurysms Using Flow 800. Oper AK, Shah QA, Hussain SI, Kabbani MR, Bulsara KR, Taqi AM, Janardhan V, Open Neurovascular Training. World Neurosurg. 2019 Feb;122:e553-e560. Neurosurg. 2019 May 1;16(5):583-592. Patterson MS, Nordhaus BL, Elijovich L, Puri AS. TARGET® Intracranial Strickland) has received further funding from the SELECT 2 trial, which evaluates the efficacy and Aneurysm Coiling Prospective Multicenter Registry: Final Analysis Gopalakrishna R, Bhat NR, Zhou S, Mack WJ. Cell signaling associated Rutkowski M, Song I, Mack WJ, Zada G. Outcomes After Minimally of Peri-Procedural and Long-Term Safety and Efficacy Results. with internalization of 67 kDa laminin receptor (67LR) by soluble Invasive Parafascicular Surgery for Intracerebral Hemorrhage: A Front Neurol. 2019 Jul 9;10:737. laminin and its implication for protection against neurodegenerative Single-Center Experience. World Neurosurg. 2019 Aug 23. pii: S1878- diseases. Neural Regen Res. 2019 Sep;14(9):1513-1514. 8750(19)32243-0.

16 CEREBROVASCULAR 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery keck.usc.edu/neurological-surgery/ Clinic (323) 442-5720 Academic Office (323) 409-7422 Keck School of Medicine of USC 17 Jonathan Russin, M.D., Associate Professor of Neurological Surgery, left, stands at the finish line of the Los Angeles Marathon with former patient Kathy Nguyen and her husband, Robby. (Photo/Mary Dacuma) INSPIRATION

n March 8, 2020, a former patient of the USC Comprehensive blood flow to the brainstem while preventing additional bleeding from the Stroke and Cerebrovascular Center ran the Los Angeles aneurysm. The USC Stroke Center is one of a handful in the country that can Marathon, accompanied by the treatment team that saved her perform this rare procedure. Immediately following the bypass, Dr. Mack and life - it was the 5th anniversary since her surgery. Prior to her his team blocked the vertebral artery and the aneurysm through endovascular stroke, 41-year-old Kathy Nguyen had nine marathons under her coiling. belt. In March 2015, Nguyen collapsed at a family brunch and was Otaken via ambulance to a local emergency room. Her doctors determined she On Friday, March 13, Nguyen woke up. “Friday the 13th has always been had serious bleeding in her brain, but could not determine the source of the my lucky day,” she said. “My twins were born on that day.” Nguyen made a bleed. remarkable recovery with strong support from her treatment team.

“The bleed was so severe that the neurosurgeon told my family I would be “Kathy’s motivation and commitment to physical fitness enabled her to engage lucky to wake up,” recalled Nguyen, a part-time realtor and former cardio in highintensity activities soon after her surgery,” said Cherise Lathan, physical kickboxing instructor. therapist at Keck Medical Center. “There are not many patients that I can push to do circuit training after a stroke. But her spirit inspired me to push myself Nguyen was transferred to Keck Medical Center of USC for evaluation by and join her for her comeback race.” their comprehensive cerebrovascular stroke team. A CAT scan helped William Mack, MD, Professor of Neurological Surgery, find the aneurysm causing the Nguyen recruited Lathan, Russin, Joseph Hendrix (physician assistant at the bleed. He quickly recognized the complexity of the problem. neurosciences clinic), administrative assistant Valerie Sanchez and Senior Director of Development Chris Sickels to run by her side. It was the first “There was a ruptured aneurysm that involved the entire left vertebral artery, marathon for all of them. including the posterior inferior cerebellar artery (PICA), which provides blood to part of the patient’s brainstem,” said Jonathan Russin, MD, Associate Nguyen also raised more than $4,800 for the USC Stroke Center. Surgical Director at the USC Neurorestoration Center. “Cutting off the blood supply to the artery would also cut off blood to the brainstem, causing brain “In addition to raising awareness for brain aneurysm research, I wanted to damage or even death.” thank my treatment team, especially all the nurses at 7 South ICU. I wouldn’t be here if it weren’t for them.” Dr. Russin performed a PICA-PICA bypass, which involves suturing the right Credit: Mary Dacuma, USC Health Sciences Media Relations and left posterior inferior cerebellar arteries (PICAs) together to ensure proper

18 CEREBROVASCULAR 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery Learn more about the USC Comprehensive Stroke and Cerebrovascular Center at: 19 https://neuro.keckmedicine.org/treatments-services/NEUROVASCULAR-DISORDER-CENTER/ Keck School of Medicine of USC brian mark darrin jennifer daniel CONDITIONS WE TREAT LEE, MD, PhD LIKER, MD LEE, MD, PhD HUI, MD TOGASAKI, MD, PhD

PARKINSON’S DISEASE and other parkinsonian syndromes

USC Deep Brain Stimulation Center ESSENTIAL TREMOR

danielle andres parastou FEIGENBAUM, MD GONZALEZ, MD SHILIAN, DO DYSTONIA

EPILEPSY or many patients with Parkinson’s disease, essential tremor, dystonia, and obsessive-compulsive disorder (under essential tremor, dystonia, or other movement a Human Device Exemption). The technique is believed to suppress TOURETTE'S SYNDROME and other tic disorders disorders, otherwise useful medications often abnormal electrical signals in the brain that are caused by these cannot prevent troublesome or even diseases, although the exact mechanism is not fully understood. ATAXIA disabling symptoms. For these The USC Deep Brain Stimulation Center at Keck patients, surgical intervention HUNTINGTON'S DISEASE with deep brain stimulation Medicine of USC in Los Angeles offers Southern California’s most comprehensive care for (DBS) is an option. OBSESSIVE-COMPULSIVE DISORDER patients requiring deep brain stimulation. Deep brain stimulation is a The Center’s team of experienced health- MYOCLONUS and other movement surgical technique in which care professionals provides the highest disorders an electrical current is quality care to patients considering DBS. It applied through an electrode placed in very also conducts advanced research in these disorders Fspecific locations in the brain, depending on and is a National Parkinson Foundation Center of the disease. DBS is approved by the Food and Excellence, one of only 34 such centers nationwide

Drug Administration (FDA) for the treatment DBS implantable generator, leads, (and the only designated center in Southern California). of several disease such as Parkinson’s disease, and lead extenders

20 21 DEEP BRAIN STIMULATION 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery keck.usc.edu/neurological-surgery/ Clinic (323) 442-5720 Academic Office (323) 409-7422 Keck School of Medicine of USC The USC Deep Brain Stimulation Center at Keck Medicine of USC is an interdisciplinary program that draws from adult and pediatric neurologists, neurosurgeons, psychiatrists, nurse practitioners, clinical psychologists, X-ray of implanted DBS leads in the subthalamic nucleus neuropsychologists and social workers. It also collaborates with the Parkinson’s Disease and Movement Disorders Center, Intraoperative Neurophysiological Monitoring Program, and the Viterbi School of Engineering.

DEEP BRAIN STIMULATION

s part of a renowned university-based medical center, members of trials program in Southern California for Parkinson’s disease and dystonia. Our the center conduct research in other projects exploring such areas commitment to providing compassionate, comprehensive and customized care as: behavioral side effects of deep brain stimulation and medication is reflected in the care we provide to our patients. Following are conditions we for Parkinson’s disease; the effect of exercise in Parkinson’s disease; commonly see at our center: treatment of dyskinesias in Parkinson’s disease; novel DBS electrode coating metallurgy; optimization of electrode placement for • Parkinson’s disease and other parkinsonian syndromes complex pediatric dystonia population; and outcomes of DBS in patients with • Essential tremor A • Dystonia Parkinson’s disease essential tremor, dystonia and obsessive-compulsive disorder. • Tourette’s syndrome and other tic disorders • Ataxia The USC Parkinson’s Disease and Movement Disorder Center at Keck • Huntington’s disease Medicine of USC is the most comprehensive center in Southern California • Myoclonus and other disorders of movement for Parkinson’s disease and other movement disorders. Our team is a unique collaboration of health-care professionals who deliver the highest quality care The USC Parkinson’s Disease and Movement Disorder Center takes a to ensure the most successful outcomes in our patients. We also are a National multidisciplinary approach to treatment. Patients receive a wide range of Parkinson Foundation Center of Excellence and home to the largest clinical medical care from our neurologists, neurosurgeons, and nurse practitioners,

22 DEEP BRAIN STIMULATION 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery keck.usc.edu/neurological-surgery/ Clinic (323) 442-5720 Academic Office (323) 409-7422 Keck School of Medicine of USC 23 but also can receive subspecialized services from surgery in order to interact with the surgeon and could cause problems during awake surgery. Keck clinical psychologists, social workers, speech report any symptoms or side effects from insertion Medicine of USC is the only center in Southern therapists, occupational and physical therapists. of the DBS leads into the brain. This technique is California to offer this advanced surgical option. As part of a major university-affiliated medical considered the "gold-standard" and has been used It’s just one part of a multidisciplinary program that center, patients can also participate in clinical for many years. At USC, we have improved upon this can be life-changing for patients with movement trials that lead to new developments in treatments. technique by performing awake surgery with the disorders. We also offer deep brain stimulation for those assistance of intraoperative 3D fluoroscopy which The Surgical Neurophysiology Program at Keck patients who are appropriate candidates having allows us to confirm the final position of the DBS Medicine of USC is unlike any surgical monitoring failed optimized pharmacotherapy. As a National electrodes before conclusion of the surgery. The program in the country; it provides all aspects of Parkinson Foundation Center of Excellence – a addition of intraoperative 3D fluoroscopy improves surgical neurophysiology to greatly reduce the risk of designation bestowed on only 34 medical centers accuracy and reduces the need for potential lead damaging key nervous system areas during surgery. nationwide – we are recognized by peer institutions revision surgery. The program consists of three parts: for our leadership in research, comprehensive Asleep MRI-guided DBS. We are proudly the only care delivery, professional education, and patient center in Southern California to offer asleep MRI- • Intra-operative monitoring outreach services. The Center is the only Center guided deep brain stimulation procedures. While • Brain mapping of Excellence in Southern California. DBS surgery has historically been performed while • Brain implants ADVANCED IMAGE GUIDANCE TECHNOLOGIES the patient is awake but sedated, this breakthrough for "AWAKE" and "ASLEEP" DBS SURGERY technique using real-time MRI guidance allows for Intra-operative monitoring reduces risk and the patient to be asleep for the entire procedure. improves outcomes during brain, spine, head and At USC we are the only center in Southern California The entire surgery is performed while the patient neck surgery or other surgeries where any part of to offer the ability to perform DBS surgery using the is inside the bore of the MRI scanner and offers the nervous system is at risk. By monitoring the traditional "awake" surgical technique and the new the unique ability to accurately visulize the DBS electrical signals of nerve cells in the brain and "asleep" MRI-guided option. leads inside the brain. This technique is well-suited spinal cord during surgery, the program at Keck Awake DBS. During the traditional awake DBS for patients with anxiety about surgery, language Medicine of USC can help prevent injuries like stroke surgery, the patient remains awake throughout the barriers, and severe tremor or dyskinesias that or paralysis during the operation. DBS leads need to be precisely positioned in the brain in order to achieve maximal symptom control.

24 25 DEEP BRAIN STIMULATION 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery keck.usc.edu/neurological-surgery/ Clinic (323) 442-5720 Academic Office (323) 409-7422 Keck School of Medicine of USC RESEARCHERS ARE CLOSING IN ON ONE OF THE MOST COMMON, AND Brain mapping localizes important functions of the brain, such as language, when stimulated with an electrical current, can ameliorate some of the patient’s COMPLEX, NEURODEGENERATIVE DISORDERS­ — PARKINSON'S DISEASE motor function, vision, and sensation - brain areas that can vary a great deal major symptoms. These devices are first activated in the operating room to between individuals. As a consequence, surgeons will know which key areas to determine the potential for adverse effects and to confirm the correct location for hen patients with Parkinson’s come balanced and customized medications, physical DBS surgical program at Keck Medicine. Dr. Lee to see Daniel Togasaki, the USC therapy and exercise, and in many cases, surgery. specializes in deep brain stimulation, or DBS. bypass when performing operations, sparing vital structures in the brain. surgical implant leading to improvement in symptoms. physician can’t prescribe a cure In this procedure, surgeons implant electrodes in Thanks to new insights in cellular biology, scientists or offer an xplanatione for how the brain and connect them to an electronic device Brain implants: We offer deep brain stimulation for the treatment of conditions Our physicians use a number of methods to measure nervous system activity are following some clues that might finally lead to a people develop the disease — but secured beneath the skin on a patient’s chest. The like Parkinson disease, essential tremor, dystonia, and obsessive-compulsive in the brain and spinal cord, using a variety of techniques including evoked cause — and solutions. They’re looking intensely at he has reason for optimism. “New device sends electricity to the brain, disrupting a type of protein found in the brain called alpha- disorder, among others. By navigating electrodes deep into the brain using a potentials, electroencephalograms, electrocorticography, and microelectrode scientific information makes me very hopeful that abnormal brain signals and allowing normal brain W synuclein. This protein may clump together in computer-guided trajectory, we are able to locate the group of neurons which, recording. we are getting to the root cause of Parkinson’s,” signals to take over. This can control many of the Parkinson’s patients, damaging cells. Scientists call says Togasaki, a Keck Medicine of USC neurologist disease’s physical symptoms, allowing patients these deposits Lewy bodies, and they’re also linked and specialist in Parkinson’s disease treatment in to cut back on medications. “It doesn’t cure the to some dementias. USC is among a select group Los Angeles. “It’s very possible, in the next five to disease, but it can make a dramatic difference in of sites for a national clinical trial of an engineered 10 years, we will have a treatment that will stop people’s lives," says Lee. antibody called prasinezumab to try to halt the DEEP BRAIN STIMULATION RESEARCH progression of the disease.” spread of alpha-synuclein proteins. This study is USC is the only medical center in Southern s part of a large university-based medical center, our physician- such as epilepsy, Parkinson’s disease, essential tremor, and dystonia. LOOKING FOR CAUSES OF just one of a variety of clinical trials for potential California that can perform DBS implantation PARKINSON’S DISEASE new treatments at the USC Parkinson’s Disease and surgery using MRI guidance while patients are scientists are involved in research projects aimed at improving • Identifying biomarkers in Parkinson's disease for use in a closed-loop Deep Movement Disorder Center, which offers the largest asleep. About 80 percent of patients now choose monitoring, deep brain stimulation and mapping capabilities, as Partly because scientists don’t yet fully understand Brain Stimulation system. the disease’s origins, there’s no definitive diagnostic number of clinical trials for Parkinson’s and other this option, Lee says. He is particularly excited well as testing new surgical techniques. Physicians at the program test for Parkinson’s. The disease itself isn’t fatal, movement disorders in Southern California. about the potential for his latest research into also have authored numerous scientific journal articles and textbook • Understanding the underlying neurophysiology of Alzheimer’s disease and but as it progresses, it can lead to disabilities and brain computer interfaces. He’s been working with chapters on scientific discoveries and advanced neurosurgical SURGEON-SCIENTISTS IMPROVE LIVES paralyzed patients to enable them to use brain developing neuromodulation techniques (deep brain stimulation, focused complications that can cause death. The process can WITH DEEP BRAIN STIMULATION techniques. Exciting research projects include: ultrasound) to treat the disease and its symptoms. take anywhere from years to decades, depending on signals to control a robotic arm. He hopes a version A The standard medication given to Parkinson’s of the technology will someday help Parkinson’s the individual. • Exploring the network changes associated with schizophrenia and working to patients, Sinemet, boosts dopamine but also patients. “This is where neural engineering and • Using Deep Brain Stimulation for neurological and psychiatric disorders such develop neuromodulation techniques to treat the disease process (deep brain As a Parkinson’s Foundation Center of Excellence induces its own kind of involuntary movements. medicine collide,” he says. “USC has made a as: Alzheimer's, depression, schizophrenia, obesity, and obsessive-compulsive stimulation, transcranial magnetic stimulation). — one of only 34 nationally — the USC Called dyskinesia, the movements look like concerted effort to bring more surgeon-scientists disorder (OCD). Parkinson’s Disease and Movement Disorder fidgeting. Eventually, the burden of juggling drugs to this campus, because at an academic medical • Investigating if deep brain stimulation can improve memory and cognition in Center hosts physician-researchers with years of and their side effects along with symptoms may center like USC, we’re trying to push the envelope. • Developing neurorestorative technologies and cognitive-based brain- Parkinson’s disease. experience with the disease. “We can do a lot to become intolerable, and that’s when patients head We don’t want to just practice medicine. We want to computer interface (BCI) devices for patients with neurological disorders, treat this,” Togasaki says. That includes carefully to neurosurgeons like Brian Lee, director of the help develop the next big thing.” Credit: Constance Sommer. This story was adapted from an article about Parkinson's disease in the Winter 2018 issue of USC Trojan Family.

26 DEEP BRAIN STIMULATION 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery keck.usc.edu/neurological-surgery/ Clinic (323) 442-5720 Academic Office (323) 409-7422 Keck School of Medicine of USC 27 INSPIRATION

ight before Robert Warner was wheeled into the operating “That was three months of thinking I wouldn’t be around to see my kids grow room at Keck Hospital of USC, his surgeon asked him to open up,” says the father of four young children. and close his hands. It took the Parkinson’s patient three seconds. Opting for a surgery that he hoped would restore some of Finally, in 2008, doctors confirmed aParkinson’s diagnosis. Warner soon his independence, Warner was about to have electrodes attached to began a regimen of exercise and medication, which worked for a while. But by his brain in a procedure called deep brain stimulation, or DBS, at November 2015, he was taking about 20 pills a day. When he tried to work RUSC. The electrodes would ultimately be connected to a box secured under the out, his leg began to twist. “I need to exercise more to get better, but I can’t skin on his chest. because these symptoms are happening,” he says.

He was awake when the surgeon turned on the electrical current. This time, He elected to undergo DBS surgery at USC to help improve his motor skills, and when his surgeon asked him to make a fist, Warner clenched his fingers the change has made a huge difference in his daily life. He dropped to six pills instantly. a day and he can exercise again. He also has been able to keep working as an engineering supervisor at Edwards Air Force Base. “I actually cried,” he says. “It was just incredible. A miracle.” “As an engineer, I spend a lot of time at my desk. Being able to type is a Warner, 44, has lived with Parkinson’s for 11 years. It was 2007 when he make-or-break thing for me,” he says. first noticed his pinkie moving on its own. He chalked it up to a shoulder injury he’d sustained in a recent triathlon, and went to see a doctor. And best of all, he’s gotten back some of his independence. He can still Robert Warner (3rd from left, wearing dark sunglasses) with marathon teammates. drive, making the two-hour drive from Tehachapi, California, to see his Keck (Photo, courtesy of Robert Warner) Thus began 14 months of consulting with physician after physician, searching Medicine physicians in east Los Angeles for regular checkups. for an answer to his increasingly debilitating symptoms. At one point, Credit: Constance Sommer, USC Health Sciences Media Relations Warner believed he had ALS, or Lou Gehrig’s disease, another degenerative neurological disease, but one that has a two- to five-year life expectancy.

28 DEEP BRAIN STIMULATION 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery Learn more about the USC Deep Brain Stimulation Center at: 29 https://neuro.keckmedicine.org/treatments-services/DEEP-BRAIN-STIMULATION-CENTER/ Keck School of Medicine of USC CONDITIONS WE TREAT FY 2020 Procedures Pediatric neurosurgical cases performed at Children's Hospital Los Angeles. susan mark j. gordon peter jason ACHONDROPLASIA USC Pediatric Neurosurgery DURHAM, MD, MS KRIEGER, MD McCOMB, MD CHIARELLI, MD, DPhil CHU, MD, MSc ARACHNOID CYSTS 171 Hydrocephalus: Shunt, Endoscopic Third Ventriculostomies bout half of all pediatric of the top children’s hospitals in the country. This year CHLA BRACHIAL PLEXUS ABNORMALITIES neurosurgical operations in Los was ranked the #5 pediatric hospital in the nation. The

magazine’s annual Best Children’s Hospital survey—accepted as the BRAIN and SPINAL CORD TUMORS 147 Angeles County are performed by Brain and Spinal Cord Tumors neurosurgeons from Children’s most definitive review of America’s pediatric medical centers—also CHIARI MALFORMATION and Hospital Los Angeles (CHLA) recognized the Division of Neurosurgery as one of the leading SYRINGOMYELIA Division of Neurosurgery. This high programs of its kind, ranking 9th overall in the nation. 93 Epilepsy volume of cases leads to high success CONGENITAL BRAIN and SPINAL CORD ABNORMALITIES rates in treatment with our experts Our pediatric neurosurgery program is among the busiest in the nation with over 700 surgical procedures and 5,000 routinely performing surgeries for CRANIOSYNOSTOSIS 50 outpatients this year, while continuing to conduct leading- Congenital: Arachnoid Cysts, complex neurological conditions. Our Neural Tube Defects patients range in age from newborns to edge research. It can take a very special team of people to provide DYSTONIA, SPASTICITY, and other movement disorders young adults. Armed with the latest technologies, the Division the very best care for children who need neurosurgery. Families

who choose care from our specialists benefit from having access to 39 provides advanced surgical solutions, with outcome statistics HEAD and SPINAL CORD TRAUMA Trauma: Head and Spinal Cord Athat match or exceed other programs across the nation and all of the specialists below under one roof, including: beyond. These therapies significantly improve outcomes for • Neurologists • Orthopedic Surgeons HYDROCEPHALUS 66 children suffering from a wide range of conditions such as brain and spinal Craniofacial • Neuro-oncologists • Otolaryngologists INTRACTABLE EPILEPSY cord tumors, deafness, hydrocephalus and medically intractable epilepsy. • Neuro-ophthalmologists • Physical Therapists NEURAL TUBE DEFECTS and Because our hospital operates the only Level I Trauma Center in Los • Neuropathologists • Psychiatrists SPINA BIFIDA 25 Functional, Dystonia Deep Brain Angeles solely for children, our neurosurgeons are well-versed in caring • Neuroradiologists • Psychologists Stimulation, Intrathecal Baclofen Pump, PITUITARY TUMORS Selective Dorsal Rhizotomy for severely injured children and have pioneered new therapies that are • Clinical Nurse Specialists • Radiation Therapists improving surgical outcomes. • Craniofacial Surgeons • Rehabilitation Therapists VASCULAR MALFORMATIONS 20 Chiari and Syrinx For the thirteenth year in a row U.S. News & World Report’s prestigious • Medical Geneticists • Urologists Honor Roll has included Children’s Hospital Los Angeles in its ranking • Occupational Therapists

30 31 PEDIATRIC NEUROSURGERY 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery keck.usc.edu/neurological-surgery/ Clinic (323) 442-5720 Academic Office (323) 409-7422 Keck School of Medicine of USC PEDIATRIC NEUROSURGERY

hese past two years has been an exciting time for the Division of The Division is pleased to welcome new additions to our faculty: Susan Durham, Neurosurgery, and we are proud to share the following highlights MD, MS, Peter Chiarelli, MD, DPhil and Jason Chu, MD, MSc. of the team’s clinical and research efforts from 2018. Following an extensive national search for a successor for the Senior Vice Dr. Durham serves as division chief of Pediatric Neurosurgery at CHLA. She President and Surgeon-in-Chief role at CHLA, Mark Krieger, MD, received her medical degree from University of Pittsburgh School of Medicine the Billy and Audrey Wilder Neurosurgery Chair and Director of and has been in practice for more than 20 years. In addition to serving as Chief, the Neurological Institute, was named to the position, after serving as interim Division of Neurosurgery CHLA, she is also Co-Director of the Neurological T Institute CHLA, Director of the Neurosurgery Fellowship Program, and holds the Surgeon-in-Chief for the Department beginning in June 2018. In this role, Dr. Krieger provides administrative and clinical leadership for the Department of J. Gordon McComb Family Chair in Neurosurgery. Surgery in alignment with the enterprise mission, vision, values and goals. He is Dr. Durham's research interests include developing evidence-based guidelines in responsible for the academic, clinical, quality, financial, research, educational pediatric neurological surgery and she is a researcher in a multi-center clinical and reputational well-being of the department. trial on Chiari 1 malformation with syringomyelia. Nationally, Dr. Krieger was elected Chair of the Pediatric Joint section of Dr. Chiarelli comes to CHLA from Seattle Children’s Hospital where he the American Association of Neurological Surgeons and the Congress of completed a fellowship in pediatric neurological surgery. Prior to that, he was Neurological Surgeons, the largest organization of pediatric neurosurgeons in a neurological surgery resident at the University of Washington. He received his the world. He was also named the Director of the American Board of Pediatric medical degree from the joint program at Harvard Medical School/Massachusetts Neurosurgery. Institute of Technology and a doctorate in Neuroscience from the University of The hydrocephalus research team, under the guidance of J. Gordon McComb, Oxford. MD with grants from both the Los Angeles Kings’ Kings Care Foundation Dr. Chu joins CHLA after completing a fellowship in pediatric neurosurgery at and the Rudi Schulte Research Institute, continues to make progress in the Texas Children’s Hospital. He completed his residency at Emory University and development of advanced imaging techniques to better diagnose and manage earned his medical degree from Saint Louis University School of Medicine. He also hydrocephalus. His work focuses on gaining a deeper understanding of its holds a Master of Science degree from the University of Toronto. pathology with the ultimate goal to develop even more enhanced treatments for this devastating disease. In recognition of his longtime dedication to hydrocephalus and its treatment, the Hydrocephalus Association recently honored Dr. McComb with a Lifetime Achievement Award.

32 PEDIATRIC NEUROSURGERY 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery keck.usc.edu/neurological-surgery/ Clinic (323) 442-5720 Academic Office (323) 409-7422 Keck School of Medicine of USC 33 Functional Neurosurgery Program symptoms. A pacemaker-like device connects The neuro-oncology team has a strong track record Earlier this year, Las Madrinas - Spanish for “The to electrodes implanted within certain areas of of conducting national and international early phase Godmothers” - announced their newest project: the brain to produce electrical stimulation that clinical trials. The team’s clinical research interests a $5 million pledge to enhance care for children regulates abnormal impulses. include designing irradiation-avoiding treatment diagnosed with neurological conditions. The latest CHLA is the largest freestanding pediatric hospital strategies for infants and young children with commitment from Las Madrinas will enable CHLA in the West performing functional neurosurgery. malignant brain tumors and innovative treatment to double the size of the Epilepsy Monitoring Unit This means that for thousands of children, we are strategies for patients with Central Nervous System and upgrade equipment to include portable and the only institution providing the care they need to (CNS) germ cell tumors. We also conduct research wireless monitoring systems to track a patient’s enjoy a life free from the physical and psychological for patients with neurofibromatosis, low grade brain activity wherever they are in the hospital, burdens of their neurological conditions. gliomas, and diffuse intrinsic pontine gliomas including during surgery and recovery. (DIPG). We study molecularly targeted therapies and

Neuro-oncology Program the role of inflammation in embryonal brain tumors Using auditory brain stem implants to give The at Children’s Neuro-oncology Program including medulloblastoma and atypical teratoid deaf children a chance to hear is just one Hospital Los Angeles treats children with brain rhabdoid tumor (AT/RT) to improve outcomes for innovative technique of the Division’s Functional tumors and spinal cord tumors, which are the these patients. Neurosurgery Program. The program also works second most common types of tumors in children. to restore function for patients with previously We are one of the largest pediatric neuro-oncology CHLA has a multi-disciplinary Neuroendocrine untreatable conditions such as seizures, movement programs in the country with more than 150 Program for coordinating care and treatment of disorders and other neurological conditions through new referrals per year from Southern California, pituitary tumors. the following therapies: nationally and internationally. Our program offers The Radiation Oncology Program at CHLA is • Epilepsy surgery: For patients whose seizures patients access to the latest treatment options an internationally recognized leader in pediatric cannot be controlled with medication, surgery is being tested in clinical trials through participation in radiation oncology and one of only two radiation the best chance at leading a seizure-free life. Using national and international research consortia. oncology programs in the nation focused exclusively a high-tech system of measuring brain waves, Every patient receives comprehensive care on children. called “brain mapping,” to pinpoint the area where from a multi-disciplinary team of physicians The Neuropathology Program at CHLA includes seizures originate, the Division partners with CHLA and nurses that include neuro-oncologists, three distinguished pediatric neuropathologists. neurologists and epileptologists to remove the neurosurgeons, neurologists, neuroradiologists, Within the Department of Pathology and Laboratory troubled area and eliminate seizures for good. Dr. Peter Chiarelli at CHLA performing an radiation oncologists, neuropathologists, neuro- Medicine also resides the Center for Personalized operation for removal of a brainstem tumor. • Deep brain stimulation: For patients suffering endocrinologists, neuro-ophthalmologists, Medicine, whose mission is to discover the human from conditions such as essential tremor and rehabilitation medicine specialists, genome’s potential to guide preventive medicine, dystonia, deep brain stimulation provides highly neuropsychologists, and advanced practice nurses, targeted therapies and personalized health care for customized treatment to target and improve who are national leaders in their respective fields. the benefit of generations to come.

34 35 PEDIATRIC NEUROSURGERY 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery keck.usc.edu/neurological-surgery/ Clinic (323) 442-5720 Academic Office (323) 409-7422 Keck School of Medicine of USC SELECTED PUBLICATIONS

Saadeh FS, Borzage M, Ponrartana Imahiyerobo TA, Johns AL, Stephen ZR*, Chiarelli PA*, Melamed EF, Rea S, Tamrazi B, Gibbs W, Christian EA, Sanchez-Lara Revia RA, Wang K, Kievit ND, Krieger MD. Nelson MD, McComb PA, Krieger MD, McComb F, Dayringer C, Jeon M, Seizure outcomes of JG, Blüml S. A new MRI JG, Urata MM. Risk Ellenbogen R, Zhang M. Time- supratentorial brain tag-based method Factors for Preoperative Resolved MRI Assessment tumor resection in to non-invasively Developmental Delay of Convection-Enhanced pediatric patients. visualize cerebrospinal in Patients with Delivery by Targeted and Nanoparticles in Human Gliobastoma Mouse Model. Photo Credit: Peter Chiarelli, MD, DPhil Neuro Oncol. 2018 fluid flow. Childs Nonsyndromic Sagittal Nontargeted Nanoparticles in Aug 2;20(9):1272- Nerv Syst. 2018 Craniosynostosis. Plast a Human Glioblastoma Mouse 1281. Sep;34(9):1677-1682. Reconstr Surg. 2019 Model. Cancer Res. 2019 Sep PEDIATRIC NEUROSURGICAL RESEARCH Jan;143(1):133e-139e. 15;79(18):4776-4786.

The hydrocephalus research team, under the novel sensory technology. The implant is designed to currently serves as a co-investigator for a pilot study Villanueva KG, Rea ND, Krieger MD. Novel Surgical and Chu JK, Feroze AH, Collins K, McGrath LB, Young CC, Williams JR, safety assessment of surgical biopsy for patients with newly guidance of Dr. McComb, continues to make measure intracranial pressure, CSF flow, and catheter with Huntington Memorial Hospital evaluating the Radiologic Risk Factors for Progression or Recurrence of Browd SR. Variation in hospital charges in patients with external diagnosed diffuse intrinsic pontine glioma. Neuro-Oncology. 2018 Pediatric Pilocytic Astrocytoma. Pediatr Neurosurg. 2019 Oct 8:1- ventricular drains: comparison between the intensive care and Oct 9;20(11):1547-1555. doi: 10.1093/neuonc/noy070. progress in the development of advanced imaging patency and is currently being tested non-invasively feasibility of a fetoscopic surgical technique for 11. doi: 10.1159/000503110. [Epub ahead of print]. surgical floor settings. J Neurosurg Pediatr. 2019 Apr 19:1-6. doi: techniques to better diagnose and manage in patients requiring external ventricular drains. This prenatal correction of fetal myelomeningocele. 10.3171/2019.2.PEDS18545. [Epub ahead of print]. Yepes Calderon F., Rea N., McComb JG (2018) Enabling hydrocephalus. The ability to visualize CSF flow novel invention could greatly increase the precision Strahle JM, Taiwo R, Averill C, Torner J, Shannon CN, Bonfield CM, Clinical Trials Tuite GF, Bethel-Anderson T, Rutlin J, Brockmeyer DL, Wellons JC, the Medical Applications Engine. Applied Informatics. and the site of obstruction on MRI is essential to of diagnosing shunt malfunction in hydrocephalic The Children’s Hospital Los Angeles Neurosurgery team Leonard JR, Mangano FT, Johnston JM, Shah MN, Iskandar BJ, Tu A, Melamed E, Krieger MD. Dynamic MRI in the Evaluation Communications in Computer and Information Science, 2018 determining what kind of operative procedure patients. is a recent addition to both the Hydrocephalus Clinical Tyler-Kabara EC, Daniels DJ, Jackson EM, Grant GA, Couture DE, of Atlantoaxial Stability in Pediatric Down Syndrome Patients. Oct;vol 942:131-143. should be performed to either correct or bypass the Research Network (HCRN) and Park-Reeves Syringomyelia Adelson PD, Alden TD, Aldana PR, Anderson RCE, Selden NR, Baird Pediatr Neurosurg. 2019;54(1):12-20. doi: 10.1159/000495788. Epub Dr. Peter Chiarelli recently founded the blockage. The team is currently utilizing a novel, non- Research Consortium (PRSRC), whose ongoing multi-site LC, Bierbrauer K, Chern JJ, Whitehead WE, Ellenbogen RG, Fuchs 2019 Jan 24. Fisher LM, Martinez AS, Richmond FJ, Krieger MD, Wilkinson EP, Nanoscaled Neuro-technology Research Group HE, Guillaume DJ, Hankinson TC, Iantosca MR, Oakes WJ, Keating invasive MR application, Time-STAMP, that allows for clinical trials aid in the management of hydrocephalus, Chiari Eisenberg LS. Assessing the Benefit-Risk Profile for Pediatric (NNRG) at CHLA. Dr. Chiarelli’s research focuses malformations, and syringomyelia: RF, Khan NR, Muhlbauer MS, McComb JG, Menezes AH, Ragheb Alexiades NG, Ahn ES, Blount JP, Brockmeyer DL, Browd SR, Grant Implantable Auditory Prostheses. Ther Innov Regul Sci. 2018 an in image that is 50 percent clearer and brighter J, Smith JL, Maher CO, Greene S, Kelly M, O'Neill BR, Krieger MD, on the development of nano-therapeutics for the GA, Heuer GG, Hankinson TC, Iskandar BJ, Jea A, Krieger MD, Sep;52(5):669-679. doi: 10.1177/2168479017741111. Epub 2017 than what current scanning methods produce. This • (HCRN): A randomized controlled trial of anterior versus Tamber M, Durham SR, Olavarria G, Stone SSD, Kaufman BA, Heuer Leonard JR, Limbrick DD, Maher CO, Proctor MR, Sandberg DI, Nov 29. treatment and cure of pediatric brain tumors. posterior entry site for CSF shunt insertion GG, Bauer DF, Albert G, Greenfield JP, Wait SD, Van Poppel MD, technique greatly improves the signal-to-noise ratio. Wellons JC, Shao B, Feldstein NA, Anderson RCE. Development The lab’s goal is the design of novel therapeutic Eskandari R, Mapstone T, Shimony JS, Dacey RG, Smyth MD, Park TS, • (PRSRC): Posterior fossa decompression with or without of best practices to minimize wound complications after Yepes-Calderon F, Nelson MD, McComb JG. Automatically Additionally, the head circumference and ventricular modalities that will one day make brain tumor Limbrick DD. Radiological and clinical predictors of scoliosis in duraplasty for Chiari type I malformation with syringomyelia complex tethered spinal cord surgery: a modified Delphi measuring brain ventricular volume within PACS using artificial patients with Chiari malformation type I and spinal cord syrinx size of patients need to be monitored to assure that surgery obsolete. In addition to his translational study. J Neurosurg Pediatr. 2018 Dec 1;22(6):701-709. doi: intelligence. PLoS One. 2018 Mar 15;13(3):e0193152. doi: 10.1371/ Grants and Endowments from the Park-Reeves Syringomyelia Research Consortium. J the hydrocephalus is under control. The research laboratory efforts, Dr. Chiarelli currently serves as 10.3171/2018.6.PEDS18243. journal.pone.0193152. eCollection 2018. • Kort Family Foundation: Brain and Spinal Cord Tumor Neurosurg Pediatr. 2019 Aug 16:1-8. doi: 10.3171/2019.5.PEDS18527. team has been developing a method to automatically clinical site Principal Investigator for the Children’s Research Program Endowment. (Krieger), $2,000,000 [Epub ahead of print]. and accurately determine both the maximum Hospital Neonatal Consortium, a multi-center Gupta N, Goumnerova LC, Manley P, Chi SN, Neuberg D, Puligandla Donoho DA, Wen T, Liu J, Zarabi H, Christian E, Cen S, Zada G, • Billy and Audrey L. Wilder Foundation: Neurosurgery head circumference and ventricular size. These national clinical research network focused on Kaneva K, Yeo KK, Hawes D, Ji J, Biegel JA, Nelson MD, Bluml M, Fangusaro J, Goldman S, Tomita T, Alden T, DiPatri A, Rubin JB, McComb JG, Krieger MD, Mack WJ, Attenello FJ. The effect of Research Program for Pediatric Brain Tumors. (Krieger), S, Krieger MD, Erdreich-Epstein A. Rare Pediatric Invasive Gauvain K, Limbrick D, Leonard J, Geyer JR, Leary S, Browd S, Wang NACHRI children's hospital designation on outcome in pediatric developments utilize automatic algorithms that improving quality and outcomes across Level IV $8,000,000 Gliofibroma Has BRAFV600E Mutation and Transiently Z, Sood S, Bendel A, Nagib M, Gardner S, Karajannis MA, Harter D, malignant brain tumors. J Neurosurg Pediatr. 2017 Aug;20(2):149- obtain the measurements from MRI studies. Current neonatal intensive care units (NICUs). He is also Responds to Targeted Therapy Before Progressive Clonal • Fineberg Foundation: Neurosurgery Research Program for Ayyanar K, Gump W, Bowers DC, Weprin B, MacDonald TJ, Aguilera 157. doi: 10.3171/2017.1.PEDS16527. Epub 2017 Jun 2. Evolution. JCO Precis Oncol. 2019;3. doi: 10.1200/PO.18.00138. efforts are aimed at a systems-wide incorporation leading CHLA’s first clinical trial investigating the Pediatric Brain Tumors. (Krieger), $175,000 D, Brahma B, Robison NJ, Kiehna E, Krieger MD, Sandler E, Aldana Epub 2019 Mar 27. of these applications in neuroradiology reports that efficacy of fluorescent-guided microscopy in the Shweikeh F, Quinsey C, Murayi R, Randle R, Nuño M, Krieger MD, • Los Angeles Kings Care Foundation: Hydrocephalus research. P, Khatib Z, Ragheb J, Bhatia S, Mueller S, Banerjee A, Bredlau Patrick Johnson J. Treatment patterns of children with spine make the results available on patient-management identification and resection of pediatric brain tumors. (McComb), $100,000/yr. Juliano J, Melamed E, Christian E, Tamrazi B, Krieger MD. Imaging AL, Gururangan S, Fuchs H, Cohen KJ, Jallo G, Dorris K, Handler systems in real-time. Features Predictive of Recurrence in Pediatric Intracranial M, Comito M, Dias M, Nazemi K, Baird L, Murray J, Lindeman N, and spinal cord tumors: national outcomes and review of the Rudi Schulte Research Institute: MRI Visualization of CSF. Dr. Jason Chu’s research interests include epilepsy, • Germ-Cell Tumors. Pediatr Neurosurg. 2019;54(3):173-180. doi: Hornick JL, Malkin H, Sinai C, Greenspan L, Wright KD, Prados M, literature. Childs Nerv Syst. 2017 Aug;33(8):1357-1365. doi: 10.1007/ Dr. Krieger and Dr. McComb continue to work with cerebrovascular disorders, pediatric head trauma, (McComb), $50,000/yr. 10.1159/000493194. Epub 2019 Mar 13. Bandopadhayay P, Ligon KL, Kieran MW. Prospective feasibility and s00381-017-3433-y. Epub 2017 May 8. Dr. Ellis Meng at the Viterbi School of Engineering to endoscopic neurosurgery, hydrocephalus, brain • AANS/CNS Pediatrics Section: Junior Faculty Grant. develop a wireless multisensory shunt system using a and spine tumors and congenital abnormalities. He (Chiarelli), $5000

36 PEDIATRIC NEUROSURGERY 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery keck.usc.edu/neurological-surgery/ Clinic (323) 442-5720 Academic Office (323) 409-7422 Keck School of Medicine of USC 37 Surgical team in OR doing the "keyhole" spina bifida surgery at Huntington Hospital. L-R, surgeons Jason Chu, Ramen Chmait, and Andrew Chon. (Photo credit: "Keyhole" Surgery Repairs Spinal Bifida in utero Business Wire)

ilda Giron was just 13 weeks pregnant openings in the abdomen and uterus, percutaneous when an ultrasound revealed her fetoscopic spina bifida repair has the potential to baby had myelomeningocele—the provide the similar benefit to the baby as compared most severe form of open spina bifida, to the standard open maternal fetal surgery a birth defect that affects backbone approach. development and can cause, among Gother things, debilitating neurological damage. “This To perform the procedure, the surgical team, used was a very emotional time for us,” says Giron, who precision tools and a camera to enter the abdomen already had two young children and was determined and womb. The uterus was expanded with carbon to protect her third. Surgeons could repair the dioxide to allow safe access to the fetus. They moved defect in the womb, but she and her husband Arnuf the exposed spinal cord back in place, patched the wanted the safest option for both mother and child. hole in the fetus’ spine, then sewed fetal skin over the While researching, they came across a promising patch. This not only protected underlying nerves and new surgical method pioneered in Brazil and FDA- stopped the spinal fluid leakage, which untreated can approved but performed only once thus far in the Ramen Chmait, MD, the principal investigator cause lower body paralysis and disrupt the bladder USA: in-utero percutaneous fetoscopic spina for the Los Angeles site in the clinical study, is a and bowels, it also prevented amniotic fluid in the bifida repair. And as luck would have it, a team CHLA Fetal-Maternal Center surgeon, an associate uterus from mixing with the fetal nervous system. of doctors was piloting a clinical study at the Keck professor of Obstetrics and Gynecology at the Keck In fact, a follow-up MRI showed Abigail’s hindbrain School of Medicine of USC, Children’s Hospital Los School and Director of Los Angeles Fetal Surgery. herniation—part of her brain that had dropped due Angeles (CHLA) and Huntington Hospital on that very CHLA pediatric neurosurgeon Jason Chu, MD, MSc, to changes in fluid pressure—had reversed, the first procedure, just miles from the Giron’s home. and pediatrician Alexander Van Speybroeck, MD, indication the operation was a success. medical director of CHLA’s Spina Bifida Program, both On February 19, 2019, Gilda became the first participated in the surgery. “Abundant research shows that if you can repair person in the western USA to undergo the most spina bifida while the child is still developing minimally invasive type of spina bifida repair While spina bifida surgery in utero has been available in the womb, you are more likely to prevent currently available for a developing fetus. The for more than 10 years, this new method refines significant developmental problems that can surgery was a success, and three months later, at previous techniques by removing the need for large occur,” says Jason Chu, who assisted with the term and without need for a C-section, Gilda gave incisions altogether. Sometimes referred to as a neurological repair and is an assistant professor of birth to Abigail, a healthy 5-pound 5-ounce baby girl. “keyhole” surgery because it requires only small Clinical Neurological Surgery at the Keck School.

38 39 PEDIATRIC NEUROSURGERY 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery keck.usc.edu/neurological-surgery/ Clinic (323) 442-5720 Academic Office (323) 409-7422 Keck School of Medicine of USC INSPIRATION

afael Hernandez shouldn’t be alive. At four months old, he survived Dr. Sanger, has treated hundreds of children suffering from the worst neurological a horrific head-on collision with a semi. His father, Ralph Hernandez, a disorders, mostly at CHLA. “I see a lot of kids with lots of different movement U.S. Marine, was killed on impact. When his mother, Mariza Hernandez, disorders, but dystonia is probably the most common, and one of the most lifted Rafael out of the wreckage, his car seat split in half. Rafael’s skull frustrating because the children are very locked in,” Sanger said. Some of the was extensively fractured. To save his life, doctors removed 46 percent children in Sanger’s care have their arms tied down to their wheelchairs so they of his brain, returning him to his mother in a vegetative state. Secondary don’t hurt themselves involuntarily. Others crawl crablike on the floor. to his brain injury, Rafael developed dystonia — a neurological movement R DBS — literally drilling into patients’ skulls and zapping the deepest structures of disorder that would further lock him inside his body, causing involuntary muscle their brains with electricity — has been used to treat more than 40,000 people spasms and painful, twisting movements. with Parkinson’s and essential tremor worldwide, and is currently undergoing “They told me he’ll never learn to sit or walk, feed himself or reach for clinical trials as a treatment for depression and obsessive-compulsive disorder. objects,” Mariza Hernandez said. “He’d be legally blind and the grand What allows Rafael Hernandez to pitch a baseball and control his body despite mal seizures could eventually kill him.” But Hernandez refused to believe missing nearly half of his brain are two thin wires with four electrical contacts at the prognosis. She held on to hope for the next 23 years, through late-night their tips, sending a finely tuned electrical pulse into a very specific and carefully ambulance rides, brain surgeries, and violent seizures. selected region of his brain. Neurosurgeons Liker and Krieger performed the “He never gained more than 91 pounds,” she said. “For 21 years, not a pound surgery while Sanger guided them to the exact targets. This wire, called the over 91!” DBS lead, reaches the deepest recesses of Rafael’s brain — the globus pallidus and the thalamus. The wire is connected to a pacemaker-like device implanted Today, at 23 years old and 140 pounds, Rafael is full of life. He dances and sings in Rafael’s chest below his collarbone. This device, contains the battery and and plays baseball. On August 5, his mother cheered him on as he pitched computer source that generates the electrical pulses delivered via the lead to in the Little League World Series in front of ESPN cameras for the Azusa the brain. Challengers, a team made up of children and young adults with disabilities. Neurologists typically split dystonia into two categories: primary or genetic Rafael, whose name means “God healed,” did more than survive, thanks to his dystonia, and secondary or acquired dystonia — like Rafael’s — caused by mother, who never gave up on him, and an emerging medical procedure called trauma to the brain or another condition such as cerebral palsy. Inherited deep brain stimulation, or DBS. The procedure, which has been around for dystonias are rare compared to acquired dystonias. years, was re-designed and perfected by USC Viterbi professor Terence “Terry” Sanger, MD, PhD and other researchers willing to cross paths and disciplines Studies suggest that only about 50 percent of children with acquired dystonia at USC Viterbi, Children’s Hospital Los Angeles and the Keck School of see a significant benefit from DBS. But Sanger and his team have recognized a Medicine of USC. That group included electrical, mechanical and biomedical significant benefit in over 70 percent of these children.“For my son, it’s been engineers; data scientists; nurse practitioners; physical therapists and some 110 percent improvement,” Mariza Hernandez said. “Since DBS, Rafael has also prominent names in neurosurgery, including Mark Liker, MD, Aaron Robison, been seizure free.” Credit: Story and photos by Daniel Druhora. This story was adapted from an article MD and Mark Krieger, MD. about DBS in the Autumn/Winter 2017 issue of USC Viterbi Magazine.

40 PEDIATRIC NEUROSURGERY 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery Learn more about the USC Pediatric Neurosurgery Program at: 41 https://www.CHLA.org/neurosurgery Keck School of Medicine of USC CONDITIONS WE TREAT Program Highlights:

2018: USC Keck became an gabriel john elisabeth bozena ACOUSTIC NEUROMA ZADA, MD, MS CARMICHAEL, MD FERENCE, MD WROBEL, MD NIH-funded center for research pertaining to the genomics CHORDOMA/CHONDROSARCOMA and epigenetics of pituitary adenomas, with grant support CRANIOPHARYNGIOMA of $2.65M

USC Minimally Invasive Neurosurgery and GLIOMA/ASTROCYTOMA Over 900 endoscopic neurosurgery cases performed since 2011 makes USC one of HYDROCEPHALUS Endoscopic Skull Base/Pituitary Center the highest volume endoscopic neurosurgery destination MENINGIOMA centers in the Western U.S.

METASTATIC BRAIN TUMORS Over 40 per-reviewed scientific ndoscopic neurosurgery is a rapidly evolving advanced technology, including high quality endoscopy systems publications in 2018-19

subspecialty that takes full advantage of the and high definition viewing monitors, into many types of PITUITARY ADENOMA New postgraduate fellowship most recent advancements in optical and neurosurgery has significantly improved our ability to in Neurosurgery: The Keck USC RATHKE’S CLEFT CYST Minimally Invasive Cranial and video technology as well as surgical perform many of these approaches on a daily basis. Skull Base Surgery Fellowship. instrumentation to treat a variety of COLLOID CYST First 2 fellows from UCSF brain tumors and other conditions We offer a comprehensive neuro-endoscopic and NYU

using minimally invasive minimally invasive surgery program, including EPIDERMOID/DERMOID TUMOR New 7 Tesla MRI available for approaches. In endoscopic endoscopic endonasal skull base surgery, studying pituitary adenomas and ARACHNOID CYST patients with Cushing’s Disease neurosurgery, small incisions and natural intraventricular neuro-endoscopy, endoscopic- Eopenings in the skull are used to safely assisted keyhole craniotomy, and minimally and adequately perform a given operation. invasive parafascicular surgery (MIPS) for sub- Using natural pathways and smaller incisions cortical lesions. USC is one of the preeminent to approach various brain regions results in teaching facilities for endoscopic neurosurgery, holding decreased injury to the brain, reduced risks of an annual resident training course for trainees from across cerebrospinal fluid leakage, and may minimize pain, risk the country, and is a leading center for major developments in of infection and the length of hospital stays. Integration of surgical simulation for endoscopic surgical training.

42 43 NEURO-ENDOSCOPIC MINIMALLY INVASIVE NEUROSURGERY 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery keck.usc.edu/neurological-surgery/ Clinic (323) 442-5720 Academic Office (323) 409-7422 Keck School of Medicine of USC ENDOSCOPIC ENDONASAL PITUITARY ENDOSCOPIC–ASSISTED “KEYHOLE” AND SKULL BASE SURGERY OPERATIONS

hese minimally–invasive (neurosurgeon) and Dr. John his subset of endoscopic procedures are used to Carmichael (endocrinologist). The procedures takes advantage treat a variety of tumors and USC Pituitary center has been a of small “keyhole” size other lesions arising at the leading destination center of care for bony windows and smaller base of the skull and in the patients with pituitary tumors and incisions to access the paranasalT sinuses. These operations related conditions for decades, having targetT area. The tumors most are typically performed through the treated over 4,000 patients in the commonly treated via keyhole nostrils and are therefore called past 3 decades. They offer the latest operations are meningiomas, "endonasal" procedures. No incisions surgical and medical therapies for craniopharyngiomas, and are made on the face and the recovery patients with a variety of conditions pituitary adenomas, in addition is typically quite rapid. Depending including nonfunctioning pituitary to several others. on the tumor, the operation may be adenomas, Cushing’s disease, and performed by one surgeon or a team acromegaly. USC is the leading site These surgeries can often be of surgeons (typically a neurosurgeon for the Pituitary Adenoma Genomic performed using a small incision in and otolaryngologist). This approach and Epigenetic (PAGE) Consortium, the eyebrow or behind the hairline, is commonly used to treat pituitary a multi-institutional NIH-sponsored which typically cannot be seen adenomas, Rathke Cleft Cysts, national effort to understand the once healed. Depending on the meningiomas, craniopharyngiomas, molecular mechanisms driving location in the brain, a keyhole and several other tumor types. Our pituitary tumor behavior. Dr. Zada approach can be performed for neurosurgeons are fellowship-trained was also lead author and editor on several types of tumors and in minimally invasive endoscopic a new textbook entitled The Atlas cysts. It is generally believed that skull base surgery. USC has one of the of Sellar and Parasellar Lesions the smaller bony openings and highest volume national experiences (Publisher: Springer). USC is one of incisions used in these approaches in performing these operations. the only centers worldwide to offer 7T result in decreased incidence MRI for clinical diagnostics of pituitary of infections and complications The USC Pituitary Center is co- microadenomas and Cushing’s such as cerebrospinal fluid (CSF) directed by Dr. Gabriel Zada disease. leakage.

44 45 NEURO-ENDOSCOPIC MINIMALLY INVASIVE NEUROSURGERY 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery keck.usc.edu/neurological-surgery/ Clinic (323) 442-5720 Academic Office (323) 409-7422 Keck School of Medicine of USC NEURO-ENDOSCOPIC MINIMALLY INVASIVE SELECTED PUBLICATIONS INTRAVENTRICULAR OPERATIONS PARAFASCICULAR SURGERY (MIPS) Rutkowski M, Zada Itamura K, Chang KE, Chang SW, Donoho DA, Bakhsheshian J, Strickland BA, G. Management Lucas J, Donoho DA, Zada G. Use of optical Jackson C, Chaichana KL, Young R, he cerebral ventricles are a inimally Invasive of Pituitary Giannotta S, Zada G. fluorescence agents Pradilla G, Chen JW, Bailes J, Zada connected series of chambers Parafascicular Surgery Adenomas Invading Prospective clinical during surgery for G. Multicenter Investigation the Cavernous validation of a meningioma pituitary adenomas: of Channel-Based Subcortical deep in the brain that produce relies on brain imaging, Sinus. Neurosurg consistency grading current state of the Trans-Sulcal Exoscopic and circulate cerebrospinal Clin N Am. 2019 scheme: association with field. J Neurooncol. 2019 Resection of Metastatic Brain neuro-navigation, access, Oct;30(4):445- surgical outcomes and Feb;141(3):585-593. doi: Tumors: A Retrospective Case fluid (CSF) throughout the nervous optics, tissue resection, 455. doi: 10.1016/j. extent of tumor resection. 10.1007/s11060-018- Series. Oper Neurosurg. 2019 Feb nec.2019.05.005. J Neurosurg. 2018 Dec 1:1-5. 03062-2. 1;16(2):159-166. system.T At times, the normal pathways Mand regenerative medicine, thereby of CSF circulation can become blocked allowing USC neurosurgeons to safely Kim-Orden N, Shen J, Or M, Hur K, Zada G, Wrobel B. Endoscopic Donoho DA, Johnson CE, Hur KT, Buchanan IA, Fredrickson Memel Z, Chesney K, Pangal DJ, Bonney PA, Carmichael JD, Zada by tumors, cysts, or other conditions, remove brain tumors and intracerebral Endonasal Repair of Spontaneous Cerebrospinal Fluid VL, Minneti M, Zada G, Wrobel BB. Costs and training results G. Outcomes Following Transsphenoidal Pituitary Surgery in the resulting in a buildup of fluid and raised Leaks Using Multilayer Composite Graft and Vascularized of an objectively validated cadaveric perfusion-based internal Elderly: A Retrospective Single-Center Review. Oper Neurosurg. hematomas that may have been Pedicled Nasoseptal Flap Technique. Allergy Rhinol. 2019 Nov carotid artery injury simulation during endoscopic skull base 2019 Mar 1;16(3):302-309. intraventricular pressure known as previously deemed inoperable due to 13;10:2152656719888622. surgery. Int Forum Allergy Rhinol. 2019 Jul;9(7):787-794. hydrocephalus. Because the ventricles Lin M, Wedemeyer MA, Bradley D, Donoho DA, Fredrickson location or size. Lin M, Bakhsheshian J, Strickland B, Rennert RC, Chen JW, Van VL, Weiss MH, Carmichael JD, Zada G. Long-term surgical are anatomically deeper structures, they Jackanich A, Tavakol S, Strickland BA, Rutkowski M, Kamel D, Gompel JJ, Young RL 2nd, Kumar PP, Coppens J, Curry WT, Zacharia outcomes following transsphenoidal surgery in patients with Carmichael JD, Weiss M, Zada G. Clinical utility of routine can be a challenge to operate within BE, Bailes JE, Zada G. Navigable Channel-Based Trans-Sulcal Rathke's cleft cysts. J Neurosurg. 2018 May 18;130(3):831-837. The procedure requires an opening postoperative morning cortisol monitoring in detecting new Resection of Third Ventricular Colloid Cysts: A Multicenter using more traditional approaches. hypothalamic-pituitary-adrenal axis insufficiency following less than the size of a dime and uses Retrospective Case Series and Review of the Literature. World endoscopic transsphenoidal surgery for sellar lesions. J Bakhsheshian J, Wheeler S, Strickland BA, Pham MH, Rennert Neuro-endoscopic approaches Neurosurg. 2020 Jan;133:e702-e710. brain mapping, neuronavigation, Neurosurg. 2019 Mar 1:1-5. RC, Carmichael J, Weiss M, Zada G. Surgical Outcomes to intraventricular conditions have Following Repeat Transsphenoidal Surgery for Nonfunctional and the BrainPath® channel tool to Tafreshi AR, Du R, Rutkowski MJ, Donoho DA, Shiroishi MS, Pituitary Adenomas: A Retrospective Comparative Study. Oper become the preferred way to treat many safely move through the natural folds Liu CJ, Kim PE, Carmichael JD, Zada G. Differential Clinical Wedemeyer MA, Lin M, Fredrickson VL, Arakelyan A, Bradley Neurosurg. 2019 Feb 1;16(2):127-135. conditions arising within the ventricular Presentation, Intraoperative Management Strategies, and D, Donoho DA, Hurth KM, Weiss MH, Carmichael JD, Zada and delicate fibers of the brain. The Surgical Outcomes After Endoscopic Endonasal Treatment of system, including colloid cysts, G. Recurrent Rathke's Cleft Cysts: Incidence and Surgical Law M, Wang R, Liu CJ, Shiroishi MS, Carmichael JD, Mack WJ, tool allows neurosurgeons to gently Cystic Sellar Masses. World Neurosurg. 2020 Jan;133:e241-e251. Management in a Tertiary Pituitary Center over 2 Decades. Oper Weiss M, Wang DJJ, Toga AW, Zada G. Value of pituitary gland arachnoid cysts, some intraventricular Neurosurg. 2019 Jun 1;16(6):675-684. MRI at 7 T in Cushing's disease and relationship to inferior displace and reposition healthy brain tumors, and some forms of Schooner L, Wedemeyer MA, Bonney PA, Lin M, Hurth K, petrosal sinus sampling: case report. J Neurosurg. 2018 Mar 1:1-5. Mathew A, Liu CJ, Shiroishi M, Carmichael JD, Weiss MH, Zada tissue when locating a tumor, instead Seltzer J, Wedemeyer MA, Bonney PA, Carmichael JD, Weiss hydrocephalus. A dime–sized hole in G. Hemorrhagic Presentation of Rathke Cleft Cysts: A Surgical Shen J, Hur K, Zhang Z, Minneti M, Pham M, Wrobel B, Zada G. M, Zada G. Outcomes following transsphenoidal surgical of cutting it, thereby lowering the risk Case Series. Oper Neurosurg. 2019 Aug 26. pii: opz239. Objective Validation of Perfusion-Based Human Cadaveric the skull is created for insertion of the management of incidental pituitary adenomas: a series of 52 Simulation Training Model for Management of Internal Carotid of complications. The BrainPath® also patients over a 17-year period. J Neurosurg. 2018 Jun 1:1-9. endoscope into the ventricle. Sometimes, Rutkowski M, Song I, Mack W, Zada G. Outcomes After Artery Injury in Endoscopic Endonasal Sinus and Skull Base Magnetic resonance imaging (MRI) of a colloid uses neuronavigation to dock on a target a procedure called an endoscopic cyst in the third ventricle. Preoperative MRI Using intraoperative neuronavigation, the Minimally Invasive Parafascicular Surgery for Intracerebral Surgery. Oper Neurosurg. 2018 Aug 1;15(2):231-238. Hemorrhage: A Single-Center Experience. World Neurosurg. 2019 third ventriculostomy (ETV) can be (top) showing a midline 20 × 16 × 20 mm lesion and creates a clear passageway appropriate sulcus is identified (second from top). Agam MS, Wedemeyer MA, Wrobel B, Weiss MH, Carmichael homogeneous ovoid mass obstructing the BrainPath® tubular retractor (top) is cannulated Dec;132:e520-e528. JD, Zada G. Complications associated with microscopic and Chesney K, Memel Z, Pangal DJ, Donoho D, Hurth K, Mathew A, foramina of Monro and abutting the septum performed to treat hydrocephalus and for surgeons to maintain access to the into the right lateral ventricle under neuronavigation Carmichael JD, Zada G. Variability and Lack of Prognostic pellucidum. Postoperative MRI (bottom) scan guidance (second from bottom). Through the endoscopic transsphenoidal pituitary surgery: experience may eliminate the need for implanting a demonstrating complete cyst resection and tumor for removal while protecting the foramen of Monro, the colloid cyst is seen with Agam MS, Zada G. Complications Associated With of 1153 consecutive cases treated at a single tertiary care Value Associated With Atypical Pituitary Adenoma Diagnosis: resolution of hydrocephalus. Credit: Gabriel overlying choroid plexus and internal cerebral veins Transsphenoidal Pituitary Surgery: Review of the Literature. pituitary center. J Neurosurg. 2018 Jun 1:1-8. doi: 10.3171/2017.12. A Systematic Review and Critical Assessment of the Diagnostic permanent CSF shunt. Zada, MD, MS. surrounding brain tissue. (bottom). Credit: Gabriel Zada, MD, MS. Neurosurgery. 2018 Sep 1;65(CN_suppl_1):69-73. JNS172318. Criteria. Neurosurgery. 2018 Oct 1;83(4):602-610.

46 47 NEURO-ENDOSCOPIC MINIMALLY INVASIVE NEUROSURGERY 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery keck.usc.edu/neurological-surgery/ Clinic (323) 442-5720 Academic Office (323) 409-7422 Keck School of Medicine of USC INSPIRATION

hen Reem Itani learned she had a brain tumor, her endo- patients typically develop high blood pressure, diabetes and frequent infections. crinologist told her the tumor was “MRI-negative,” meaning If untreated, the disease can be fatal. it didn’t appear on a brain scan, a concept unfamiliar to “These tumors are typically 2 to 3 millimeters in diameter, while the Itani even after years in medical school and residency. “I Zada said. “When just started crying,” said the 28-year-old pediatrics resident from pituitary gland is several cubic centimeters in volume,” surgeons go in to remove the tumor, we often have very little information about Chicago. “You never hear about an MRI-negative tumor in its specific location from the IPSS report.” Wmedical school.” Hoping for a better explanation, Itani sought the counsel of her former professor, Gabriel Zada, a neurosurgeon and associate professor of This can be problematic, he said, because many important structures surround neurosurgery at the Keck School of Medicine of USC, where she received her MD the pituitary gland, including the basilar and carotid arteries. Missing the tumor in 2015. could also lead to pituitary failure or other surgical complications such as cerebrospinal fluid leakage, which can cause meningitis. Zada and his colleague John Carmichael of the USC Pituitary Center officially diagnosed her with Cushing’s disease. The condition is caused by a pituitary Itani’s case presents a hopeful prospect for future Cushing’s patients: safer microadenoma, or very small tumor, which results in chronically elevated diagnosis and surgery as high-resolution scanners become ubiquitous. “The 7T cortisol. may save patients an invasive procedure, and makes my job easier because Zada and Carmichael sought the assistance of neuroradiologists at the Mark and it lets me know exactly where the tumor is in the gland. We can be very Mary Stevens Neuroimaging and Informatics Institute (INI). They decided to test selective about just removing the tumor and not damaging the rest of the Zada said. out the INI’s new ultrahigh field 7 Tesla Magnetic Resonance Imaging scanner — gland,” which uses a more powerful magnet to produce clearer images than standard Since her surgery, Itani has made a remarkable recovery. Her cortisol levels are scanners — on Itani, and were able to successfully image and localize her tumor normal, her hair is growing back and she feels great. As she gears up for her third with the scan. year in residency, she plans to relay the experience to her colleagues during their annual case report exercise. Itani has identified two major takeaways: a medical This was the first time a 7T had been used to scan a Cushing’s patient in lesson and a personal one, which is already changing the way she interacts with the U.S. The new technology has the potential to replace the standard method of her pediatric patients. diagnosis, which is much more invasive. Itani’s case was published in the Journal of Neurosurgery, providing an early example of how the INI’s new high-resolution “I had never really been a patient before,” Itani said. “So now, when you’re scanner can help ease patient suffering and even save lives. “It’s clear that this is on the other side of things, you start to have even more sympathy for the beginning of a new frontier for ultrahigh field MR technologies,” said Arthur people who are struggling with life-threatening health conditions. Reem Itani, right, a medical resident and USC alumna, Toga, director of the INI. “The enhanced image quality opens many doors for speaks with neuroradiologist, Meng Law, MD at the Keck neuroscientists in both research and clinical settings.” “You realize just how scary it is,” she said. School of Medicine of USC. (Photo/James Stanis) Cushing’s disease comprises a specific set of symptoms, including weight gain, Credit: Story by Zara Greenbaum and photo by James Stanis. This story was adapted from skin bruising, hair loss, and in women, irregular or missed periods. Over time, an article about the diagnosis and treatment of brain tumors in the USC News.

48 NEURO-ENDOSCOPIC MINIMALLY INVASIVE NEUROSURGERY 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery Learn more about the USC Minimally Invasive Neurosurgery and Endoscopic Skull Base/Pituitary Center at: 49 http://neuro.keckmedicine.org/treatments-services/minimally-invasive-neurosurgery-and-endoscopic-skull-base-center/ Keck School of Medicine of USC CONDITIONS WE TREAT

j. peter arun ACUTE ISCHEMIC STROKE GRUEN, MD AMAR, MD INTRACEREBRAL HEMORRHAGE

SUBARACHNOID HEMORRHAGE

USC NeuroTrauma and NeuroCritical Care TRAUMATIC BRAIN INJURY

SEIZURES

niversity of Southern California Neurosurgeons care for cord injured patient arrives and after a neurologic assessment and review SPINAL CORD TRAUMA patients with spinal cord, brain, and nerve injuries at of imaging determine if the patient needs emergency surgery or hospital Los Angeles County, Keck, Children's, and other affiliated admission or can go home with outpatient follow up. STATUS EPILEPTICUS hospitals. The immense volume of trauma victims (25% in Los PERIPHERAL NERVE INJURY Angeles County come to LAC+USC) provides an incomparable Emergency surgery for placement of intracranial pressure monitors or drains learning experience for the medical students, advanced or to reduce pressure from brain swelling or expanding blood clots is done practitioners, interns, residents, and nurses on neurosurgery almost daily. More than 300 patients are admitted to the Neuroscience and other services. ICU each year, and the dedicated neurosurgery OR performs more than 100 neurotrauma, cranial and spinal, surgeries are performed each year, making UCONTINUUM OF CARE USC Neurosurgery one of the busiest neurotrauma services in the country. Neurotrauma care along the continuum of an injury from resuscitation in the field to societal reintegration is delivered in both the inpatient and outpatient The Neuroscience ICU is collaboratively managed by neurosurgery and settings by a multidisciplinary team of specialists. In collaboration with neurocritical care teams led by Attending physicians Board-certified in Rancho Los Amigos National Rehabilitation Center, LAC+USC is applying for a neurocritical care. grant to develop a traumatic brain injury (TBI) model system that will develop excellent care along the entire injury continuum. Neurotrauma works closely with Acute Care Surgery because almost half of brain or spinal cord injured patients also have life-threatening chest, LAC+USC Neurosurgery works with Los Angeles County's Emergency abdomen, or extremity trauma. The American College of Surgeons surveyors Medical Services (EMS) Los Angeles County to optimize pre-hospital care. who re-certified LAC+USC as a Level 1 Trauma Center complimented Neurosurgeons are in the Emergency Room shortly after a brain or spinal neurosurgery for our contributions to high quality trauma care.

50 51 NEUROTRAUMA and NEUROCRITICAL CARE 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery keck.usc.edu/neurological-surgery/ Clinic (323) 442-5720 Academic Office (323) 409-7422 Keck School of Medicine of USC n average, a third to half of the 20-rooms NEURORESTORATION brachial plexus exploration, sural nerve harvest, and in the Neuroscience (NS) ICU are Quality Improvement interposition grafting. Cranial trauma procedures occupied by brain or spinal cord injury • ACS Survey (ACS?) The 2018 Survey was an include external ventricular drain and ICP bolt victims. Every morning the Neurotrauma opportunity for USC Neurotrauma to showcase the placement, craniotomy evacuation of hematoma, Liaison supervises the management of quality of care we deliver. LAC+USC was re-certified and decompressive craniectomy. Repair of spinal Oneurotrauma patients both in the NS and Surgical as a Level 1 Trauma Center. fluid leakage during cervical or lumbar spine Intensive Care Units. Multidisciplinary Rounds with • Morbidity and Mortality Conferences. surgery can be practiced using a simulation model nursing, PT (Physical Therapy) and OT (Occupational Continuing regular reviews of complex cases to developed with the FTDL staff. Therapy), nutrition, pharmacy, Social Work, and identify areas for improvement. Utilization Review, help coordinate patient and • Neurotrauma Critical Care Conference. family support and plan for rehabilitation, skilled • Improvement projects. A number of A weekly neurotrauma critical care teaching nursing, or return to home and work. improvement projects are underway including: conference open to all providers discusses problematic cases and research projects. After discharge, patients who can safely return 1. Pressure injury reduction home are seen in brain injury outpatient clinics at • Neurotrauma Critical Care Symposium both Keck Hospital and LAC+USC. In addition to 2. Improved communication between Acute Care Post-Concussion Syndrome, these USC Neurotrauma Surgery and Neurosurgery YEARLY HALF-DAY CONFERENCE clinics provide care, support, and guidance by • ATLS. The Advanced Trauma Life Support (ATLS) EDUCATION patients suffering from disabling cognitive and sponsored on the USC Health Sciences campus by Education of medical students, training of interns emotional symptoms due to Post-traumatic Stress the American College of Surgeons Course offered to and residents, continuing education of nurses. Disorder (PTSD) and Post-ICU Syndrome. residents. • SCCM. Dr. Peter Gruen is the administrative The LAC+USC Brain Injury Clinic - Neurocritical Neurotrauma and neurocritical care education editor of the Society of Critical Care Medicine's Care and Neurosurgery Faculty. In operation • Fresh Tissue Dissection Lab Fundamental Critical Care Support (FCCS) Chapter for more than 10 years, the Brain Injury Clinic has Many procedures done to treat cranial, spinal, on Neurosurgical ICU and teaches the section on provided comfort to patients who suffer from pain, or nerve trauma are taught and practiced in the Ethics at the USC FCCS annual course. The FCCS emotional distress, and cognitive dysfunction. Fresh Tissue Dissection Lab (FTDL). The tissue of course is open to Neurosurgery residents. unembalmed cadavers refrigerated shortly after At Keck Hospital, USC Neurotrauma is working death is close to living tissue in consistency and • Annual USC Trauma Symposium with a growing group of Occupational Therapy, toughness. The Lab is equipped with surgical This year's 27th Symposium organized by the Acute Neuroophthalmology, and Social Work brain injury instruments. In the lab, students and trainees Care Surgery service is a two-day review of all specialists. can practice surgeries for nerve injuries, such as aspects of trauma care.

52 NEUROTRAUMA and NEUROCRITICAL CARE 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery keck.usc.edu/neurological-surgery/ Clinic (323) 442-5720 Academic Office (323) 409-7422 Keck School of Medicine of USC 53 OUTREACH Our mission is accomplished in the setting of a hemorrhage, is being developed and tested in • Think First. USC Neurotrauma started a local safety net medical center that provides culturally collaboration with Acute Care Surgery. chapter of this national brain and spinal cord injury sensitive emotional and spiritual support to our that works with local high schools to educate young community, emphasizing not only treatment and • Spinal Cord Injury. Early Hemodynamic people about how to enjoy activities safely. rehabilitation but also injury prevention. Management of Patients following Acute Spinal Cord Injury (TEMPLE trial). Maintain perfusion of the • Survivors Reunion. This year's LAC+USC Trauma RESEARCH spinal cord. Survivors Reunion was held on a Saturday in May. Research is important to maintaining USC's Almost a hundred survivors and their families came leadership role in neurotrauma and neurocritical • BOOST. A consortium of major academic trauma to thank the hospital and trauma providers. Several care. centers is working to encourage multi-center trials. brain and spinal cord injured patients who have gone • Pressure injuries. Dr. William Padula, formerly LAC+USC is a possible site for a multi-center study back to productive lives at school and work gave at Johns Hopkins, recently at the USC Schaeffer of monitoring of brain tissue oxygenation in severe testimonials about the excellent in- and outpatient Institiute, is an international authority on pressure TBI. care they received at Los Angeles County and injury prevention and management, is submitting Rancho Los Amigos Rehabilitation Hospital. a multi-million dollar Department of Defense grant VISION proposal for pressure ulcer prevention for immobile USC Neurotrauma will continue to advocate • Brain Injury Association. The Brain Injury brain injured comatose, and paralyzed spinal cord for patients in the Los Angeles community with Association provides information, education and injury patients, with a USC Neurosurgeon as co- traumatic brain, spinal cord, and nerve injuries at support to assist patients currently living with principal investigator. Keck and LAC+USC with the focus on building a traumatic brain injury and their families. • China collaboration. USC Neurosurgery is synergistic multi-disciplinary collaboration through • NeuroTrauma Center. The mission of the collaborating on several TBI and SCI research continuous quality care improvement, provider LAC+USC NeuroTrauma Center is to: 1) be a model projects with hospitals in China. education, and research. of state-of-the art patient-centered care, 2) provide education to patients, families and providers, and • ECMO. A neuroprotective protocol for patients 3) contribute peer-recognized research to the brain receiving extracorporeal membrane oxygenation and spine injury literature. (ECMO), at risk for brain ischemia and/or

54 NEUROTRAUMA and NEUROCRITICAL CARE 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery keck.usc.edu/neurological-surgery/ Clinic (323) 442-5720 Academic Office (323) 409-7422 Keck School of Medicine of USC 55 CONDITIONS WE TREAT and FY 2020 Procedures TREATMENTS WE PROVIDE Spine and spinal cord cases performed at Keck Medical Center of USC, ADULT SPINAL DEFORMITY Verdugo Hills Hospital, Garfield Hospital, and Good Samaritan Hospital. CERVICAL DISC INJURIES

john jeffrey thomas patrick raymond CHORDOMA LIU, MD WANG, MD CHEN, MD, PhD HSIEH, MD HAH, MD 13,760 COMPLEX RECONSTRUCTIVE SPINE Clinic Visits SURGERY COMPLEX SPINE DISORDERS 1,129 USC Spine Center DEGENERATIVE DISC DISEASE Surgeries

christopher mark david DEGENERATIVE SPINE DISORDERS ORNELAS, MD SPOONAMORE, MD CHENG, MD EVALUATION of NEUROMUSCULAR 1,463 FUNCTION Interventional Procedures FAILED BACK SYNDROME he USC Spine Center uses a and tailor procedures to each patient’s INTRADURAL TUMORS comprehensive, multi- condition and anatomy. MINIMALLY INVASIVE SPINE SURGERY Patients are evaluated at one of four locations: disciplinary approach NECK and BACK SURGERY combining specialists in Medical students, residents, fellows and USC Healthcare Center 4 PHYSICAL MEDICINE and REHABILITATION surgeons come from all over the world neurosurgery, orthopedics, Keck Medicine of USC, REVISION SPINAL RECONSTRUCTION neurology, physical medicine, to learn leading-edge techniques at the Beverly Hills SCHWANNOMA and rehabilitation, physical USC Spine Center. Current and former Keck Medicine of USC, 1808 Verdugo Blvd., Glendale therapy, pain management, international fellows have hailed from SCOLIOSIS Keck Medicine of USC, Pasadena and radiology. We pride institutions including Sohag University in SPINAL CORD INJURY ourselves on state-of-the- Egypt, Nanjing Medical University in China, SPINAL CORD TUMORS Bogang Spine Hospital in Korea, Spinal art surgical and non-operative spine care that SPINAL DISC HERNIATIONS Injuries Center in Japan, China Medical patients receive. SPINAL FRACTURE University Hospital in Taiwan, and National T SPINAL INFECTION Our clinicians deliver evidence-based medicine Institute of Rehabilitation in Mexico. We SPINAL INJECTIONS and attempt to treat patients with non-operative recently announced a joint affiliation with approaches whenever possible. The expert, Tongde Hospital of Zhejiang Province in SPINAL ONCOLOGY fellowship-trained surgeons at the USC Spine China. SPINAL STENOSIS Center can address all pathologies of the spine SPINE REVISION SURGERY SPONDYLOLISTHESIS

56 57 SPINE and SPINAL CORD 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery keck.usc.edu/neurological-surgery/ Clinic (323) 442-5720 Academic Office (323) 409-7422 Keck School of Medicine of USC MINIMALLY INVASIVE SPINAL SURGERY

ur spine surgeons are experts in will work with patients and families to ensure they from MISS to minimize the morbidity associated with minimally invasive surgical techniques have a thorough understanding of the procedure recovery from a traditional open procedure. and have all completed subspecialty and recovery. MISS procedures achieve comparable fellowships. We offer a robust training outcomes to open procedures in terms of restoring After a traditional single level lumbar fusion, it program for residents and fellows in biomechanics and reducing pain long term. is common for patients to take pain medication neurosurgery and orthopedic surgery. for six to eight weeks after the procedure. After a OIn addition, approximately 10-15 international minimally invasive lumbar fusion, most patients fellows come to the USC Spine Center each year are weaning off of pain medication two weeks after to train in MISS. All of our faculty are engaged in the procedure. MISS also results in cost savings an active research and publication program, with to hospitals, providers, and patients compared to recent manuscripts published in Journal of Clinical traditional surgical procedures. Neuroscience, Journal of Neurosurgery: Spine, Neurosurgery Clinics of North America, and World Surgeons at the USC Spine Center are at the forefront Neurosurgery, to name a few. of MISS and have been instrumental in developing new techniques, including a minimally invasive Each patient receives an individualized assessment Instead of using a standard retractor that disrupts variation on a standard procedure to decompress of their spinal anatomy and disorder to determine the muscles of the spinal column, MISS uses foraminal stenosis that can be performed as a single if a minimally invasive surgical procedure is a tubular retractor to create a port to move outpatient procedure, and a minimally invasive appropriate. The mission of the USC Spine Center is instruments in between the muscle fibers. The lateral lumbar interbody fusion. The USC Spine to deliver appropriate spine care, with physicians altered surgical technique allows many MISS Center is committed to remaining at the leading considering all other options before performing procedures to be performed on an outpatient basis. edge of minimally invasive procedures for spinal surgery. When surgery is deemed the best As the demographic in the United States ages, older disorders. Our goal is to use the latest technology to treatment option, the team at the USC Spine Center patients who are still physically active may benefit advance the care of our patients.

58 SPINE and SPINAL CORD 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery keck.usc.edu/neurological-surgery/ Clinic (323) 442-5720 Academic Office (323) 409-7422 Keck School of Medicine of USC 59 NON-OPERATIVE MANAGEMENT OF SPINAL DISORDERS

e welcome and evaluate patients help them understand their body and how they studies on each patient to determine if the nerves who are at any stage in their can adapt their current activities to minimize any are functional. If a patient is a candidate for a spinal treatment for spinal disorders. discomfort. Close collaboration among a team of cord stimulator, they will undergo a two-phase Patients don’t need to have a prior clinicians ensures that patients receive a thorough implantation. MRI to be referred to us. Patients assessment and are treated by the appropriate with a prior failed surgery or prior provider. In phase one, electrodes are placed percutaneously failed injection are welcomed. When necessary, into the epidural space and connected to the W The USC Spine Center considers all available modes simulator, which is worn externally for one week. patients can be co-managed with surgical and non- operative care and transition smoothly between the of treatment for the non-operative management This trial phase allows the surgeons to evaluate any specialties at the USC Spine Center. of spinal disorders. Spinal pain of an arthritic anatomic considerations for the permanent spinal origin can often be treated successfully with cord stimulation and the patient’s response to We realize pain that presents in the spinal area physical therapy and steroid injections. Radicular electrode placement and stimulation. In phase two, can have different origins, including a neurologic, pain can often be treated successfully with epidural the patient returns to have the permanent leads, the arthritic or muscular origin, and we perform a full steroid injections and physical therapy. Myofascial stimulator and the battery implanted. As the tissues evaluation of non-spinal causes of the pain and pain can often be treated successfully with physical heal following surgery, the patient is reevaluated dysfunction. To achieve this, we tailor the therapy and an injection of local anesthetic in trigger periodically to determine if the stimulation treatment paradigm and pain management points. program should be adjusted to provide better pain paradigm to each patient’s diagnosis. management. Physicians are well versed in treating patients with We work diligently to identify those patients who a prior failed spine surgery using non-operative To complement their clinical expertise, physicians at would likely benefit from a particular procedure methods, including spinal cord stimulation (SCS). the USC Spine Center are conducting research into and minimize the use of unnecessary diagnostic or Many times, patients present already with nerve new methods for the non-operative management therapeutic procedures. injury, prompting surgery. In this subset of patients, of spinal disorders. One area that is of particular surgery does not fully alleviate the pain from the interest to our physicians is the use of new injectable Clinicians in the multidisciplinary USC Spine Center injury and SCS is then considered. Physicians at the materials to treat spinal disorders, including stem educate patients about their spinal conditions to USC Spine Center will perform nerve conduction cells and platelet-rich plasma.

60 SPINE and SPINAL CORD 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery keck.usc.edu/neurological-surgery/ Clinic (323) 442-5720 Academic Office (323) 409-7422 Keck School of Medicine of USC 61 TREATMENT OF ADULT SCOLIOSIS AND DEFORMITY COMPLEX CERVICAL SPINAL DISORDERS Multidisciplinary care scoliosis, kyphosis, spondylolisthesis, flat-back deformity,

omplex disorders of the cervical spine place hardware in these delicate areas. When conditions, such as cervical myelopathy. Cervical Adults with scoliosis and other spinal deformities ankylosing spondylitis and post-traumatic deformity, can be serious conditions that need to possible, our surgeons will perform a laminoplasty spondylotic myelopathy (CSM), one of the most can benefit from the multidisciplinary approach among other conditions. be properly managed by specialists. instead of a spinal fusion to attempt to preserve serious conditions of the entire spine, is a disease offered at the USC Spine Center. Adults of any State-of-the-art treatments When cervical disorders are not properly spinal mobility for the patient. of insidious onset that has a subtle presentation. age can be treated for their scoliosis or back The USC Spine Center specializes in offering patients with treated from the beginning, patients can If CSM is not treated appropriately and promptly, deformity. Patients receive coordinated care adult scoliosis and deformity the option of minimally develop more complex disorders. The the patient may suffer disastrous consequences, from spine surgeons, podiatrists, physiatrists, invasive surgical procedures, including lateral interbody consequences of improper treatment of cervical such as gait disturbances and loss of coordination. vascular surgeons, occupational therapists and C physiotherapists within the USC Spine Center. approaches combined with percutaneous pedicle screw disorders can be high, including motor and sensory Conservative (non-operative) treatments are not augmentation. These minimally invasive procedures have impairment. To guard against the development of very effective at ameliorating the motor and sensory We also offer supportive programs for patients a lower risk of complications, and patients generally more serious, complex cervical spine disorders and disturbances associated with CSM. when applicable, including lifestyle modification recover faster from surgery. Our team is experienced in functional deficits, it is important that the patient be and psychotherapy. Our physicians work with managing complex cases, including patients who need assessed fully and treated appropriately. Recent studies showed that surgical decompression endocrinologists and rheumatologists to optimize revision surgeries for their deformity. to treat CSM was associated with improvements the patients’ bone quality using pharmacotherapy. Physicians at the USC Spine Center specialize in patients’ functional and quality of- life outcomes The multidisciplinary team at the USC Spine Center Other advanced surgical options offered for patients in treating disorders of the cervical spine and compared to baseline. Both anterior and posterior considers the patient’s quality of life, the severity with spinal deformity include intraoperative stereotaxic understand the nuances that are involved in treating surgical approaches appear to be equally effective of the deformity and the patient’s treatment history navigation to increase the surgical efficiency and patient patients with these conditions. Each year, we in treating CSM. This procedure is associated before deciding on a management strategy. safety associated with placing hardware. During scoliosis treat more than 500 patients who have complex with complication rates of 15 to 18 percent, of surgery, blood loss is managed with a strategic protocol, disorders of the cervical spine. which the most common complications Non-operative treatments offered at the USC including self-directed donation and intraoperative and were dysphagia, superficial infection, and Spine Center include physical therapy, medical anesthetic blood-saving strategies. Sometimes, the most conservative treatment cardiopulmonary issues. management, epidural injections and facet joint for a cervical spine disorder is surgery because injections. In addition to the traditional posterior surgical approach, it is associated with the best patient outcomes; The physicians of the USC Spine Center are leading our surgeons will use anterior, oblique and lateral delaying surgery can be associated with åthe patient Our expertise in the treatment of cervical spine the field for treatment of these and other complex Surgery is reserved for patients who are still surgical approaches to maximize the extent of deformity developing serious complications. Image-guided disorders encompasses everything from more spinal disorders. We are conducting research for affected by the deformity despite having received correction and enhance fusion potential. Each patient will navigation allows surgeons to perform procedures common conditions, such as herniated disc or novel technologies and therapeutics that will make maximal non-operative treatment. Our surgeons be evaluated carefully to arrive at a customized operative on the upper cervical spine and the occiput and degenerative disc disease, to more complex a clinical impact and improve patients’ lives. have extensive experience treating patients with plan to ensure the best clinical outcome.

62 SPINE and SPINAL CORD 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery keck.usc.edu/neurological-surgery/ Clinic (323) 442-5720 Academic Office (323) 409-7422 Keck School of Medicine of USC 63 The USC Spine Center houses a robust research program that combines leading clinical, translational and basic science research on all aspects of spine care, including disc degeneration, spinal fusion, spinal tumors and spinal cord injury. and environmental factors to bone remodeling. Mice with sham surgery had normal function. These This research is examining how risk factors affect findings will be used in future studies to help patients the function of stems cells in vitro and the healing with spinal cord injury. process in animal models in vivo. RESEARCH AT THE USC SPINE CENTER Another research project is looking at the use of Retrospective analyses of national database discs, and radiculopathy. Available data on the tissue engineering in spine care. One study involves The results from our retrospective studies provide major surgical outcome and rates of revision of the use of stem cells and nucleus pulposus (NP) solid evidence for physicians and patients to lumbar discectomy vary significantly, making it cells of the intervertebral discs to regenerate the decide on the best treatment option. challenging to advise patients on the optimal tissue, with the hopes of minimizing the need for treatment strategy. Results of our study indicated extensive surgery and potentially preventing the Treatment of thoracolumbar fractures is that the revision rate was 3.95 percent at three adjacent segment disease. challenging and can have an impact on further disc months and 12.2 percent at four years after surgery. degeneration. Our study evaluated patients The most common revision surgeries included fusion Another study is examining 3D-printed scaffolds New advance in treating acute spinal cord injury who sustained a thoracic or lumbar fracture and and discectomy. Additionally, one in three patients that are designed to mimic the extracellular matrix, Spinal cord injury treatment is often hampered Newly designed laminar cover were treated with fusion or conservative (non- who underwent multiple discectomies required a providing both structural support and improving NP by lack of treatment under acute conditions. Dr. In-vivo experiments are currently underway to surgical) management. The incidence of disc fusion within four years of the index procedure. cell attachment and proliferation. Camelia Danilov has recently demonstrated that demonstrate the feasibility of laminar covers degeneration and revision surgery (fusion) over miR133b, a microRNA that targets fibrous tissue, (shown above) to be used in human patients. a three-year period were recorded. Results Translational research in bone biology Other research includes the development of anti- can be used in conjunction with a carrier called Currently patients undergoing laminectomies do showed that an initial fusion surgery for a thoracic To complement the extensive clinical studies, tumor proteins to modulate the effect of growth Argonaute-2, to decrease fibrous scar tissue not have a cover over their spinal cord after a fracture was not associated with an increased researchers at the USC Spine Center are also factors that are important in spine tumors and formation after spinal cord injury. Prevention of spinal decompression. Dr. Tom Chen will soon to incidence of degeneration or a need for future conducting numerous basic science studies, bone regeneration. Basic research in the spinal scar tissue formation allows the spinal cord to be implanting laminar covers in-vivo in animals to fusion surgery. However, patients who sustained a Another retrospective study examined the frequency a few of which are discussed here. One of the cord is also focusing on microRNA 133b (miR133b) regenerate faster and more completely. Mice (shown determine if the laminar covers can be helpful in lumbar fracture and had initial fusion surgery and type of revision surgeries after single-level major research directions aims to improve our as a promising target to induce corticospinal tract above) given miR133b intravenously were found to preventing scar tissue formation after a laminectomy, had an increased likelihood of disc degeneration discectomy. Lumbar discectomy is a commonly understanding of bone biology and the contribution (CST) axon regeneration and improve motor function have better recovery of their gripping and landing providing cosmesis, and enabling repeat surgeries to compared to patients treated conservatively. performed procedure for herniated or degenerated of stem cells, growth factors, small molecules, outcome. function compared to the miR negative control. be performed safer.

64 65 SPINE and SPINAL CORD 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery keck.usc.edu/neurological-surgery/ Clinic (323) 442-5720 Academic Office (323) 409-7422 Keck School of Medicine of USC SELECTED PUBLICATIONS

Pham MH, Bakhsheshian Vartanian ED, Lynn JV, D'Oro A, Buser Z, Brodke DS, Bakhsheshian J, Sizdahkhani The USC Spine Center treats all patients with primary and metastatic spine tumors. Our physicians have a strong interest J, Reid PC, Buchanan IA, Perrault DP, Wolfswinkel EM, Park JB, Yoon ST, Youssef S, Ohiorhenuan I, Buchanan Fredrickson V, Liu JC. Kaiser AM, Patel KM, Carey JA, Meisel HJ, Radcliff KE, IA, Strickland B, Pham MH. Evaluation of C2 pedicle JN, Hsieh PC, Wong AK. Hsieh P, Wang JC. Trends Transpedicular lag screw in treating patients with spine tumors as early as possible in the course of the disease. Patients can be successfully screw placement via Risk Factors Associated and Costs of External placement in traumatic the freehand technique with Reconstructive Electrical Bone Stimulators cervical spondylolisthesis: treated before they have urgent or emergent needs related to the spine tumors, or when they have few symptoms. by neurosurgical Complications Following and Grafting Materials in Case report and systematic trainees. J Neurosurg Sacrectomy. Plast Reconstr Anterior Lumbar Interbody review of the literature. Spine, 2018 Jun 8: 1-6. Surg Glob Open. 2018 Nov Fusion. Asian Spine J. 2018 J Clin Neurosci. 2019 May; doi: 10.3171/2018.1.SPINE- 5;6(11):e2002. doi: 10.1097/ Dec;12(6):973-980. doi: 63:256-262. doi: 10.1016/j. 17875. GOX.0000000000002002. 10.31616/asj.2018.12.6.973. jocn.2019.01.036.

Strickland BA, McCutcheon IE, Chakrabarti I, Rhines LD, Weinberg Arshi A, Park HY, Blumstein GW, Wang C, Buser Z, Wang JC, Shamie AN, Buchanan IA, Lin M, Donoho DA, Ding L, Giannotta SL, Attenello F, COMPREHENSIVE DIAGNOSIS AND TREATMENT OF SPINE TUMORS JS. The surgical treatment of metastatic spine tumors within the Park DY. Outpatient Posterior Lumbar Fusion: A Population- Mack WJ, Liu JC. Venous Thromboembolism After Degenerative intramedullary compartment. J Neurosurg Spine. 2018 Jan;28(1):79-87. Based Analysis of Trends and Complication Rates. Spine (Phila Pa Spine Surgery: A Nationwide Readmissions Database Analysis. doi: 10.3171/2017.5.SPINE161161. 1976). 2018 Nov 15;43(22):1559-1565. doi:10.1097/BRS.000000000000- World Neurosurg. 2019 May;125:e165-e174. doi: 10.1016/j. Individualized care of all spine tumor types maximizing the treatment in one surgery. We offer one of only a few institutions in the United States 2664. wneu.2019.01.029. Fredrickson VL, Patel A, Pham MH, Strickland BA, Ohiorhenuan I, We have expertise in a wide range of primary spine a variety of state-of-the-art treatments, allowing performing robotic spine tumor surgery. The Chen T. Spine Surgery Complicated by an Engorged Lumbar Epidural Strickland B, Lewis CS, Pham MH. Bilateral vertebral artery occlusion Simcox T, Antoku D, Jain N, Acosta F, Hah R. Frailty Syndrome and the Venous Plexus from Cerebrospinal Fluid Overshunting: A Case Report after cervical spine fracture dislocation. World Neurosurg. 2019 Jan 23. Use of Frailty Indices as a Preoperative Risk Stratification Tool in tumors, including chordomas, chondrosarcomas, our physicians to tailor the right treatments to a procedure is ideal for tumors that are deep within and Review of the Literature. World Neurosurg. 2018 Mar;111:68-72. doi: pii: S1878-8750(19)30128-7. doi: 10.1016/j.wneu.2019.01.033. Spine Surgery: A Review. Asian Spine J. 2019 Jun 3;13(5):861-873. doi: 10.1016/j.wneu.2017.12.027. 10.31616/asj.2018.0239. and spinal cord tumors. The incidence of patient’s unique needs. a cavity, as the robotic access provides better Butler AJ, Alam M, Wiley K, Ghasem A, Rush Iii AJ, Wang JC. Endoscopic metastatic spine tumors is increasing due to better visualization of these tumors than would be obtained Pham MH, Bakhsheshian J. Posterolateral cervical transpedicular Lumbar Surgery: The State of the Art in 2019. Neurospine. 2019 Paholpak P, Shah I, Acevedo-Moreno LA, Tamai K, Buser Z, Wang JC. corpectomy for the surgical management of metastatic tumor. Eur Mar;16(1):15-23. doi: 10.14245/ns.1938040.020. Thoracic spine disc degeneration, translation, and angular motion: medical management of the primary disease, leading Intraoperatively, surgeons often use an O-arm® otherwise. The benefits of this procedure are that Spine J. 2018 Apr;27(4):827-832. doi: 10.1007/s00586-018-5466-7. An analysis using thoracic spine kinematic MRI (kMRI). J Clin Neurosci. Buchanan IA, Min E, Pham MH, Donoho DA, Bakhsheshian J, Minneti 2019 Aug;66:113-120. doi: 10.1016/j.jocn.2019.05.006. to an improvement in cancer survival. Coordinated intraoperative imaging system to more it is less invasive, with smaller incisions than a Arshi A, Wang C, Park HY, Blumstein GW, Buser Z, Wang JC, Shamie M, Zada G, Giannotta SL, Hsieh PC, Liu JC. Simulation of Dural Repair care is delivered from a multidisciplinary team at accurately determine where instruments and traditional surgical procedure. Patients often have a AN, Park DY. Ambulatory anterior cervical discectomy and fusion is in Minimally Invasive Spine Surgery With the Use of a Perfusion-Based Barkoh K, Ohiorhenuan IE, Lee L, Lucas J, Arakelyan A, Ornelas C, associated with a higher risk of revision surgery and perioperative Cadaveric Model. Oper Neurosurg (Hagerstown). 2019 Mar 29. pii: opz041. Buser Z, Hsieh P, Acosta F, Liu J, Wang JC, Hah R. The DOWN the USC Spine Center, consisting of oncologists, hardware are placed in the tissue. To remove shorter hospital stay after robotic surgery for a spine complications: an analysis of a large nationwide database. Spine J. doi: 10.1093/ons/opz041. Questionnaire: A Novel Screening Tool for Cervical Spondylotic 2018 Jul;18(7):1180-1187. doi: 10.1016/j.spinee.2017.11.012. Myelopathy. Global Spine J. 2019 Sep;9(6):607-612. doi: neurosurgeons, neurologists and radiation metastatic tumors in the vertebral body, surgeons tumor. Shah I, Wang C, Jain N, Formanek B, Buser Z, Wang JC. Postoperative 10.1177/2192568218815863. Ajiboye RM, Park HY, Cohen JR, Vellios EE, Lord EL, Ashana AO, Buser complications in adult spinal deformity patients with a mental oncologists. The team meets biweekly to discuss prefer using a posterior, posterolateral, or Z, Wang JC. Demographic Trends in the Use of Intraoperative illness undergoing reconstructive thoracic or thoracolumbar Paholpak P, Formanek B, Vega A, Tamai K, Buser Z, Wang JC. The complex cases. Community physicians can submit retropleural approach to spare the patient the When treated early, patients with spine tumors Neuromonitoring for Scoliosis Surgery in the United States. Int J Spine spine surgery. Spine J. 2019 Apr;19(4):662-669. doi: 10.1016/j. most appropriate cervical vertebra for the measurement of Surg. 2018 Aug 15;12(3):393-398. doi: 10.14444/5046. spinee.2018.10.003. occipitocervical inclination parameter: a validation study of case information to the team to receive a medical post-operative issues associated with an anterior may be able to retain their neurological function C3, C4, and C5 levels using multi-positional magnetic resonance Agarwal A, Schultz C, Goel VK, Agarwal A, Anand N, Garfin SR, Paholpak P, Abedi A, Chamnan R, Chantarasirirat K, Tamai K, Buser Z, imaging. Eur Spine J. 2019 Oct;28(10):2325-2332. doi: 10.1007/s00586- opinion on treatment. approach. and have a better quality of life than if the treatment Wang JC. Implant Prophylaxis: The Next Best Practice Toward Wang JC. Kinematic evaluation of thoracic spinal cord sagittal 019-06028-8. is delayed. More treatment options are often Asepsis in Spine Surgery. Global Spine J. 2018 Oct;8(7):761-765. doi: diameter and the space available for cord using weight-bearing 10.1177/2192568218762380. kinematic magnetic resonance imaging. Spinal Cord. 2019 Pham MH, Buchanan IA, Lewis CS, Fredrickson V, Kammen A, Treatment options for primary and metastatic spine Robotic spine tumor surgery available to patients at an earlier stage in the Apr;57(4):276-281. doi: 10.1038/s41393-018-0198-4. Bakhsheshian J, Acosta FL. Use of a Reverse Bohlman Technique Passias PG, Hasan S, Radcliff K, Isaacs R, Bianco K, Jalai CM, Poorman GW, for Low-Grade Spondylolisthesis. Int J Spine Surg. 2019 Oct 31;13(5): tumors span the range of radical tumor resection Robotic surgery is an emerging area for management disease, including less invasive surgical Worley NJ, Horn SR, Boniello A, Zhou PL, Arnold PM, Hsieh P, Vaccaro AR, Min E, Barbaro MF, Chen J, Liu C, Lee B. Delayed Small Bowel 486-491. doi: 10.14444/6065. Gerling MC. Arm Pain Versus Neck Pain: A Novel Ratio as a Predictor of Incarceration Within a Lumbar Burst Fracture After Posterior Spinal to minimally invasive surgery, with the aim of of spine tumors at the USC Spine Center. We are procedures. Post-Operative Clinical Outcomes in Cervical Radiculopathy Patients. Fusion: A Case Report. Cureus. 2019 May 21;11(5):e4708. doi: 10.7759/ Int J Spine Surg. 2018 Oct 15;12(5):629-637. doi: 10.14444/5078. cureus.4708.

66 SPINE and SPINAL CORD 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery keck.usc.edu/neurological-surgery/ Clinic (323) 442-5720 Academic Office (323) 409-7422 Keck School of Medicine of USC 67 INSPIRATION

er back problems started gradually, with a twinge here and area. The approach typically results in less blood loss during surgery, lowered there, but quickly escalated. Karen Sartoris couldn’t get on the risk of wound infection and postsurgical complications, less pain and shorter elliptical at the gym for five minutes, without a searing electric recovery time. shock running down her back and legs, and her feet going numb. Karen describes herself as “pretty desperate” at her first meeting with Hsieh, in “It just kept getting worse and worse,” she recalls. Karen Sartoris was fall 2013. When the staff asked about her quality of life, she burst into tears. By athletic her whole life, including cycling, running and playing fast- then, she was unable to walk to her mother-in-law’s home, five houses away. Hpitch softball. “I love the wind in my hair,” she says. But all of her beloved sports fell by the wayside. Nothing helped — not over-the-counter medication, pain The solution: a transforaminal lumbar interbody fusion. To repair her specialists, acupuncture, cupping (an ancient Chinese procedure said to draw degenerated discs, Hsieh began with two small incisions in her back, into which toxins from the body) or even surgery to address two herniated discs. he inserted tiny tubes, then an endoscope. He stabilized the back portion of her lumbar spine, with metal rods and screws, as well as a bone graft alongside the A friend told her to go see Neurosurgeon Patrick C. Hsieh, MD, quality director spine bones. He replaced the damaged vertebrae, with a bone graft spacer. As of the USC Spine Center at Keck Medicine of USC and professor of clinical the grafts healed, the newly mended spine would fuse. neurological surgery at the Keck School of Medicine of USC. “He can fix anything,” she says. The friend had known a woman who fell from a second-story balcony Hsieh encourages patients to do their research and get a second opinion, when and crushed her spine but recovered. Hsieh was her physician. “I wanted the facing spinal surgery. “We frequently see people who have been told somewhere best doctor,” Karen says. “I found him.” else that they are not candidates for minimally invasive surgery,” he says. “That’s not necessarily true — it depends on the institution’s capabilities.” At Hsieh is a specialist in minimally invasive spine surgery at the USC Spine Keck Medicine, those capabilities are backed by a research program aimed at Center, which has one of the highest volumes of cases in the region, giving its miniaturizing endoscopic technology even more, to allow additional surgeries surgeons invaluable experience. on an outpatient basis. Clinical trials using similar minimally invasive surgical Keck Medicine surgeons use minimally invasive surgical techniques for a techniques are underway, with the hope that recovery can be improved and comprehensive range of conditions — from degenerative disc disease, such the number of serious complications, such as spinal fluid leaks, meningitis and as Karen experienced (the most common procedure), to herniated discs and headaches, can be reduced. spinal stenosis (narrowing) to spinal trauma, infection, complex tumors, and Karen went home from Keck Hospital of USC, after a few days, and began her multilevel spinal deformities. rehabilitation. The first day, she walked to the front door, then the porch, then The advantages of minimally invasive surgery are numerous. Open procedures the sidewalk. These days, she has her athletic life back. To protect her new call for larger incisions and muscle stripping, as surgeons push aside the muscles spine, she decided to forgo volleyball, running and softball. Instead, she upped of the spinal column in order to operate. Minimally invasive procedures use her cycling time and took up swimming and a new sport: pickleball — a paddle small incisions, perhaps an inch in length, through which the surgeon can insert sport that combines elements of tennis, badminton and ping-pong. “I feel very specialized instruments to obtain a magnified and illuminated view of the surgical fortunate,” Karen says. “There’s nothing bad about being a success story.” Credit: Candace Pearson, USC News

68 SPINE and SPINAL CORD 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery Learn more about the USC Spine Center at: 69 https://spine.keckmedicine.org/ Keck School of Medicine of USC CONDITIONS WE TREAT Important Milestones:

1979: Stereotactic brachytherapy gabriel steven arun peter william cheng BRAIN METASTASES ZADA, MD, MS GIANNOTTA, MD AMAR, MD GRUEN, MD MACK, MD YU, PhD for malignant lesions of the brain using Iridium-192 MENINGIOMAS radioactive seeds embedded in plastic afterloading ribbons PITUITARY ADENOMAS 1986: Linear accelerator USC Radiosurgery Center ACOUSTIC NEUROMAS (LINAC)-based stereotactic eric shelly adam jason radiosurgery with 4-MV CHANG, MD BIAN, MD GARSA, MD YE, MD photons at the USC/Norris CRANIOPHARYNGIOMAS Comprehensive Cancer Hospital and Research Institute, which CHORDOMAS was the first institution west of Boston to develop a concept TRIGEMINAL NEURALGIA through hardware and software he USC Radiosurgery Center, co-directed by Gabriel technologies. Having access to these two modalities for stereotactic research radiosurgery allows USC physicians to individualize treatment ARTERIOVENOUS MALFORMATIONS Zada, MD (Neurosurgery) and Eric Chang, 1994: Leksell Gamma Knife® MD (Radiation Oncology) has been among plans for a wide variety of diseases with the utmost installed at the USC University the nation’s preeminent radiosurgical accuracy and safety. Hospital centers for more than four decades, 1995: Stereotactic radiosurgery and continues to innovate in As the only institution in Southern California of the spine

the application of radiosurgical to offer these technologies in one location, 1999: The 1000th patient received treatments for brain, spine and systemic our physicians are able to provide patients stereotactic treatment at the USC diseases.T with the best possible course of treatment. Each one is designed to support more favorable 2000: The most advanced The multidisciplinary center includes results while minimizing both side effects and Leksell Gamma Knife® Model C installed at the USC University neurosurgeons, radiation oncologists, length of treatment. All of these procedures are HospitaL physicists and medical oncologists, and uses conducted without an incision or general anesthesia, 2009: Gamma Knife Perfexion cutting-edge radiosurgery capabilities including and without the need for a hospital stay. installed at Keck Hospital the most advanced Gamma Knife and TrueBeam of USC as the only current Perfexion machine in Los Angeles County

70 71 STEREOTACTIC RADIOSURGERY 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery keck.usc.edu/neurological-surgery/ Clinic (323) 442-5720 Academic Office (323) 409-7422 Keck School of Medicine of USC USC physician-scientists have been among the pioneers of radiosurgical treatments for the past several decades, having treated over 6,000 brain lesions in the past 2 decades.

Vestibular Schwannoma extending into the internal auditory meatus and pressing on STEREOTACTIC RADIOSURGERY the brain stem. (Photo credit: Elekta)

ur program remains in the forefront of innova- The team has published results showing more than 95 percent tive applications of radiosurgical treatments tumor control over five years for a majority of tumor types. for brain, spine and systemic diseases. Many of the innovations in stereotactic surgery Using a team approach toward diagnostics and treatment of were invented or refined at Keck Medicine patients with brain and spine tumors, our multi-disciplinary team of USC. The technology that preceded the offers patients the most advanced and sophisticated radiosurgi- original CyberKnife® robotic surgical system was invented cal treatments. Every week, neurosurgeons, radiation oncologists O and experienced physicists meet to determine the best treat- at USC. Additionally, our physicians helped create stereo- tactic frames for the head and other equipment that made ment options for our patients. The specialists in the program, navigation through the skull, brain and spine more precise who include physicians at Keck Hospital of USC and the USC during Gamma Knife® procedures. Norris Comprehensive Cancer Center, have performed thousands of procedures with the Gamma Knife® (including the latest The USC Stereotactic Radiosurgery Center at Keck Medi- Perfexion model), and TrueBeam™ Stx. When used appropri- cal Center of USC is considered one of the nation’s lead- ately, the Gamma Knife® and other radiosurgical modalities ing centers for Gamma Knife® and other incision-free are very safe complements to conventional surgery and techniques in the treatment of brain and spine tumors. chemotherapy.

72 73 STEREOTACTIC RADIOSURGERY 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery keck.usc.edu/neurological-surgery/ Clinic (323) 442-5720 Academic Office (323) 409-7422 Keck School of Medicine of USC TREATMENTS AND SERVICES Gamma Knife® radiosurgery is a non-invasive makes no incision. It combines data from three- The TrueBeam™ Stx radiotherapy system is a non- alternative to traditional brain surgery, directing a dimensional computer imaging studies with a invasive system that delivers powerful radiation to precise beam of radiation to the targeted area of stereotactic head frame to precisely focus radiation. even more precise areas than possible with other the brain. For many conditions, treatment using technologies, in the head and neck, lung, liver and the Gamma Knife® Perfexion – is among the most The Leksell Gamma Knife was installed and made other areas. The TrueBeam™ Stx system can target accurate form of stereotactic radiosurgery available. operational at the USC University Hospital in 1994 tumors and other disorders in areas close to critical and upgraded in 2000 with the installation of the structures in the body and direct a precise beam With it, 192 beams of cobalt-60 radiation are Leksell Gamma Knife 3 and again in 2009 with the of radiation without harming those structures. In delivered through the skull to a small and critically Leksell Gamma Knife Perfexion. The Gamma Knife addition, a treatment of radiation therapy using the located area inside the skull, to stop or alter tissue procedure is typically delivered on an outpatient TrueBeam™ Stx system can take just a few minutes, growth. The Gamma Knife® contains no blade and basis. minimizing patient discomfort.

SELECTED PUBLICATIONS

Diao K, Sun Y, Yoo SK, Yu C, Ye Routman DM, Bian SX, Diao Tavakol S, Jackanich A, JC, Trakul N, Jennelle RL, Kim K, Liu JL, Yu C, Ye J, Zada Strickland BA, Marietta PE, Zada G, Gruen JP, Chang G, Chang EL. The growing M, Ravina K, Yu C, Chang EL. Safety-net versus private importance of lesion volume EL, Giannotta S, Zada G. hospital setting for brain as a prognostic factor in Effectiveness of Gamma Knife metastasis patients treated patients with multiple brain Radiosurgery in the Treatment with radiosurgery alone: metastases treated with of Refractory Trigeminal Disparities in follow-up care stereotactic radiosurgery. Neuralgia: A Case Series. Oper and outcomes. Cancer. 2018 Cancer Med. 2018 Mar;7(3):757- Neurosurg (Hagerstown). 2019 Jan 1;124(1):167-175. doi: 10.1002/ 764. doi: 10.1002/cam4.1352. Oct 17. pii: opz311. doi: 10.1093/ cncr.30984. Epub 2017 Sep 13. Epub 2018 Feb 14. ons/opz311.

Diao K, Bian SX, Routman Diao K, Bian SX, Routman Tucker DW, Gogia AS, Donoho Tang AM, Bakhsheshian J, DM, Yu C, Ye JC, Wagle NA, DM, Yu C, Kim PE, Wagle NA, DA, Yim B, Yu C, Fredrickson Lin M, Jarvis CA, Yuan Wong MK, Zada G, Chang Wong MK, Zada G, Chang VL, Chang EL, Freidman E, Buchanan IA, Ding L, EL. Stereotactic radio- EL. Combination ipilimumab RA, Zada G, Giannotta SL. Strickland BA, Chang E, surgery and ipilimumab for and radiosurgery for brain Long-Term Tumor Control Zada G, Mack WJ, Attenello patients with melanoma metastases: tumor, edema, Rates Following Gamma Knife FJ. Readmission following brain metastases: clinical and adverse radiation Radiosurgery for Acoustic inpatient stereotactic outcomes and toxicity. J effects. J Neurosurg. 2018 Neuroma. World Neurosurg. radiosurgery for brain tumors. Neurooncol. 2018 Sep; 139 Dec 1;129(6):1397-1406. 2019 Feb;122:366-371. doi: J Radiosurg SBRT. 2019; (2):421-429. doi: 10.3171/2017.7.JNS171286. 10.1016/j.wneu.2018.11.009. 6(2):101-119.

74 STEREOTACTIC RADIOSURGERY 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery Learn more about the USC Radiosurgery Center at: 75 http://neuro.keckmedicine.org/treatments-services/stereotactic-radiosurgery-center/ Keck School of Medicine of USC CONDITIONS WE TREAT

steven thomas c. josh patrick c. gabriel frank frances apostolos hee-yeon camelia GLIOMAS: GIANNOTTA, MD CHEN, MD, PhD NEMAN, PhD HSIEH, MD ZADA, MD, MS ATTENELLO, MD CHOW, MD STATHOPOULOS, CHO, PhD DANILOV, PhD MD, PhD astrocytomas, brainstem gliomas, ependymomas, gangliogliomas, glioblastoma multiforme, medulloblastomas, mixed gliomas, oligodendrogliomas, optic nerve USC Neuro-Oncology gliomas radu steve weijun nicholas john l. paul e. eric nagore isabel MINEA, MD SWENSON, PhD WANG, MD TRAKUL, MD, PhD GO, MD KIM, MD CHANG, MD MARÍN RAMOS, PhD METASTATIC CANCER: brain cysts, choroid plexus papillomas, CNS lymphoma, cystic tumors, dermoid tumors, germinomas, lymphoma, metastatic tumors n the United States, more than 17,000 new oncology program requires close collaboration and (melanoma, breast, lung, prostate), pineal tumors cases of primary brain tumors and 6,000 expertise in all of these therapeutic modalities. spinal cord tumors are diagnosed each year. This expertise is available at the Neuro-Oncology SKULL BASE TUMORS: The Neuro-Oncology Program at Keck Medical Program at Keck Medicine of USC. acoustic neuroma, adenomas, Center of USC and the Norris Comprehensive chordomas, craniopharyngiomas, epidermoid tumors, meningiomas, Cancer Center has an internationally The USC Neuro-Oncology Program offers a pituitary tumors, Rathke’s cleft cyst recognized team of expert clinicians and comprehensive approach to caring for patients with brain and spinal tumors, bringing together renowned researchers who are focused on fighting SPINAL CORD TUMORS: Ibenign and malignant tumors. medical neuro-oncologists, radiation oncologists, astrocytomas, ependymomas, radiologists and neurosurgeons to provide patients meningiomas, schwannomas, metastatic tumors The team at the Brain and Spine Tumor Center with a broad range of treatment options. Such an provides exemplary patient care and develops approach can be of great benefit to patients, not novel therapies in a multidisciplinary fashion. Brain only during the initial diagnosis but at any point and spinal tumors come in a great variety of types, during treatment. Our patients benefit from having each requiring a different approach to treatment physicians that collaborate as a team, which that may require medical, surgical or radiation- introduces best-practice medical decisions and based intervention. As a result, an effective neuro- streamlines patient care.

76 77 NEURO-ONCOLOGY 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery keck.usc.edu/neurological-surgery/ Clinic (323) 442-5720 Academic Office (323) 409-7422 Keck School of Medicine of USC at the and RESEARCH GLIOMA RESEARCH GROUP LABORATORY OF CANCER NEUROSCIENCE Minea is an expert in integrin biology, integrin- 4. Assisting team members with identification of LABORATORY OF CANCER NEUROSCIENCE targeted polypeptides, and engineering bacterial drug level uptake and tissue specificity Josh Neman, PhD is an Assistant hosts for enhanced production of protein biologics. Professor of Neurological Surgery, GLIOMA RESEARCH GROUP Hee-Yeon Cho, PhD spearmint, cherries, and celery seeds) and its anti- His research interests are to: 5. Development and testing of novel ovarian Physiology & Neuroscience, Director of Dr. Cho’s areas of expertise are oxidant and anti-inflammatory effects after spinal 1. Understand the contribution of extracellular cancer therapies delivered intraperitoneally Thomas Chen, MD, PhD, is Professor Cancer Biology & Genomics Doctoral molecular and cellular biology, cancer trauma. The role of POH in neurotrauma is not well of Neurosurgery, Pathology, and matrix to cancer spheroid biology and Weijun Wang, MD Program, Member of the Norris Comprehensive biology, and protein biochemistry. Dr. understood and more research is needed in this metastasis into the brain. Orthopedic Surgery, the Director of Cancer Center at the Keck School of Medicine of Cho’s research goal is to find better therapies for the field. Ongoing studies in the neuro-oncology group Dr. Wang has more than 12 years of the Surgical Neuro-oncology Program, USC, and Scientific Director of the USC Brain Tumor treatment of recurrent malignant gliomas. have identified the potential of POH to increase the 2. Develop novel radiopharmaceuticals experience as an oncologist, and a and the Director of the Glioma Research Group, Center. cell permeability making it an excellent candidate and nanoparticle solutions for targeted tumor certified clinical research professional an alliance of USC laboratories dedicated to Her lab developed a new drug, NEO214, that as a carrier for delivering other drugs after spinal radioablation and multimodal imaging. for human gliomas treatment. developing treatments for central nervous system Dr. Neman received his doctoral degree at the UCLA is effective against hard-to-treat gliomas. Her trauma. tumors. By combining the expertise of specialists David Geffen School of Medicine in neurobiology. research focuses mainly on testing in vitro and Steve Swenson, PhD Dr. Wang has extensive experience in establishing in cellular and molecular biology, radiation and He then went on to complete his cancer biology in vivo anticancer effects of the drug, finding its Radu Minea, MD Dr. Swenson’s research interests are varied human disease animal models, including surgical treatments of gliomas, the Glioma Research fellowship at the City of Hope’s Beckman Research cytotoxic mechanisms, and its effect on tumor Dr. Minea received his MD from Carol to develop and translate to the clinic experimental orthotopic metastatic brain tumor, Group is a multidisciplinary unit uniquely suited Institute where he was a California Institute for microenvironments. Davila University in Romania and did novel anti-cancer therapeutics. He has Parkinson’s disease, and nasopharyngealcarcinoma. Regenerative Medicine (CIRM) Fellow. to pursuing new treatments for this devastating postdoctoral studies in Immunology at extensive experience with animal models of human disease. Dr. Chen has pioneered a number of Camelia Danilov, PhD UCLA, and Biochemistry and Molecular Biology at disease and injury. His current research projects Currently, Dr. Wang focuses on translational Dr. Neman’s current research at USC investigates innovative treatments for malignant gliomas and Dr. Danilov’s main focus is on identifying USC where he developed a number of recombinant include: research under the guidelines of SOPs, FDA the biology of breast to brain metastases and spine oncology. mechanisms of neuroprotection and polypeptides with anti-metastatic properties. 1. Development of integrin targeted radiotherapy and ICH/GCP regulations in the development of pediatric brain tumors. His expertise and strengths neuronal regeneration following a spinal Although his primary scientific training is in for the treatment of gliomas. innovative drug delivery system target and new Dr. Chen is primarily interested in drug development, in stem cell biology and neuroscience have allowed cord injury. Specifically, Dr. Danilov is interested in molecular biology and the recombinant production chemotherapeutic agents for CNS related disorders, novel delivery methodologies to the brain and spinal him to develop novel molecular, cellular, and understanding the molecular biology of a subclass of protein biologics, 2. Identification of the breakdown products in like, viral vector mediated gene therapy for stage cord, and new translational treatment strategies systems approach to study the interaction between of RNAs called microRNAs and how they can be Perillyl alcohol derivatives of temozolamide IV glioblastoma Multiforme (GBM), novel agents for for brain and spine cancer. He has been involved Dr. Minea’s current research interests focus on the brain and cancer cells (termed the tumor targeted for spinal cord treatment. neurodegenerative Parkinson’s diseases, and in numerous clinical trials and his goals are to take the development of assays and in vivo models to 3. Development and evaluation of a novel to apply molecular imaging for brain tumor microenvironment)–a bidirectional interplay poorly the discoveries from the Glioma Research Group In addition, Dr. Danilov is pursuing the use of better understand the contribution of integrins and treatment strategy for melanoma involving a monitoring. understood. Dr. Neman has been the recipient of and move them into the clinic for Phase I/II trials for perillyl alcohol (POH, natural substance isolated extracellular matrices to the process of metastatic triconjugate of perillyl alcohol-TMZlinoleate multiple research awards including from National neuro-oncology patients. from the essential oils of lavender, peppermint, colonization of the brain and leptomeninges. Dr. (triple compound) Institutes of Health/ National Cancer Institute,

78 79 NEURO-ONCOLOGY 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery keck.usc.edu/neurological-surgery/ Clinic (323) 442-5720 Academic Office (323) 409-7422 Keck School of Medicine of USC CIRM, American Cancer Society, American Brain we aim to uncover novel mechanisms used by the Patrick C. Hsieh, MD Frank Attenello, MD, MS The laboratory specifically leveragesCRISPR, a USC BRAIN TUMOR CENTER Tumor Association, STOP Cancer, METAvivor, Susan nervous system which: Dr. Hsieh has a strong interest in the Dr. Attenello graduated from Yale novel molecular tool allowing highly specific The USC Brain Tumor Center (USC BTC) is responsible G Komen Breast Cancer Foundation, and the U.S. 1. Give tumors outside the brain (breast, advancing the surgical treatments of University with a Bachelor’s and modulation of gene expression in human cortical for leading and advancing the brain tumor and Department of Defense. melanoma, lung), the proclivity to grow and metastatic and primary spine tumors. Masters of Science degrees in Molecular cells and brain tumor cells. We utilize CRISPR to advanced neuro-oncology therapeutics service line, metastasize (spread) to the brain. Over the last 8 years, he has been able to develop Biochemistry and Biophysics. He received his simultaneously modulate gene function of thousands building multidisciplinary involvement across the Dr. Neman is strong supporter of involving a robust complex spine tumor program at USC Keck medical degree from Johns Hopkins University, of lncRNA targets, thus identifying lncRNAs that Keck Medicine of USC academic medical enterprise, the community in his basic and translational 2. Allow pediatric brain tumors Medical Center. Working closely with oncologists, while also functioning as a Howard Hughes Medical can be targeted to improve patient outcomes. Most including the Norris Comprehensive Cancer Center laboratory—this involves engaging with patients, (medulloblastoma) to metastasize radiation oncologists, neuroradiologists, and Institute medical research fellow. He subsequently recently, the laboratory has specifically identified and the world-renowned Stevens Neuroimaging and patient advocates, and their families’. Along with (spread) from the brain. surgical oncologists USC, he has developed a completed his neurosurgical residency at USC new lncRNA genes that increase the efficacy of Informatics Institute and the Zilkha Neurogenetic the American Brain Tumor Association, he currently successful multidisciplinary spine tumor program with a research/postdoctoral fellowship in brain standard chemotherapy. This will ultimately result in development of Institute, leading world-class preclinical, organizes annual Brain Tumor 5K walk and at USC that receives referrals for complex spine tumor genetics at the University of California, San improved strategies for treatment of brain tumor translational and clinical research programs, education day at the University of Southern tumors throughout Southern California. Dr. Hsieh is Francisco. Dr. Attenello is involved in leadership The laboratory's work has been published in Science, patients. For more information on Dr. Neman recruiting key clinicians and researchers, training the California’s campus. Furthermore, he serves particularly interested in the treatment of primary of the USC Neuroscience Outcomes Research Cancer Discovery, and Genome Biology, as well as and his research endeavors, please visit the next generation of clinician-scientists, and acquiring on the Board of Directors of Susan G Komen, Los spine tumors such as chordoma and spinal cord Group, characterizing treatment of tumors and multiple editorial pieces in Science Translational laboratory’s website at: cancerneuroscience.org external endorsement and philanthropic support to Angeles County. tumors. other neurological diseases in US national data. Medicine. ensure the continued growth and development of Gabriel Zada, MD, MS the USC Brain Tumor Center. Under the direction of Dr. Neman, the laboratory He is recognized as a leading expert in the surgical The Attenello laboratory focuses on neural stem Frances Chow, MD Dr. Zada is the Co-director of the of Cancer Neuroscience, is a translational treatment of spinal and sacral chordomas nationally cell responses to cortical injury and glioblastoma, Dr. Frances Chow specializes in neuro- USC Pituitary Center, Director of Vision and Aims research lab focused on raising awareness at and internationally. He is leading efforts to improve a highly aggressive brain tumor. Progress in both oncology and provides expertise the Endoscopic Skull Base Surgery To develop the leading multidisciplinary destination transdisciplinary investigation between cancer the treatment and clinical outcomes of chordoma neural injury and brain tumor treatments have in the treatment of primary brain Program, and Director of the USC Brain Tumor center for comprehensive brain and central nervous and neuroscience foundations can advance our and spine tumors through clinical research and been largely limited due to global research focus tumors. She collaborates with experts at USC’s Brain Center. He has a keen clinical and academic system tumor therapeutics in the Western U.S. and current understanding of how the nervous system collaboration with other scientists at USC. on classical genetic targets – genes that form and Spine Tumor Center to provide exceptional interest in brain and skull base tumor surgery, and Southern California. contributes to primary and metastatic brain proteins. These classical genes comprise only patient-centered care, offer clinical trials featuring tumors. has published over 100 peer-reviewed articles on Much of his work has focused on advancing innovative therapies, and discover novel treatments 20% of the human genome. We focus on a novel The USC Brain Tumor Center is the leading clinical, various neurosurgical topics, mostly relating to brain minimally invasive surgical treatments for spine through translational research. Dr. Chow is class of genes, long noncoding RNAs (lncRNAs), academic and educational destination site for Specifically, by leveraging current advances and pituitary tumors as well as endoscopic skull tumors. Most recently, he was able to collaborate interested in systemic and tumor microenvironment genes comprising the remaining 80% of the human patients and medical/surgical trainees, driven in neurodevelopment and the brain’s base surgery. Dr. Zada’s research interests are on the with USC urologists to be one of the first in the responses to immunotherapy and identifying genome, and providing a very promising pool of by unsurpassed patient outcomes and cutting- microenvironment (neurons, astrocytes, role of epigenetic modification in pituitary adenomas country to successfully excise several spine tumors pathways of acquired resistance in glioblastoma. potential genetic targets in brain injury and tumor edge research. On the clinical side, the combined oligodendrocytes, microglia, cerebral spinal fluid), and their role in tumorigenesis and progression. using the Da Vinci robot. treatments.

80 81 NEURO-ONCOLOGY 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery keck.usc.edu/neurological-surgery/ Clinic (323) 442-5720 Academic Office (323) 409-7422 Keck School of Medicine of USC multidisciplinary program will include internationally models pioneered at USC. We aim to establish delivery approaches (e.g. convection Clinical Affairs care across integrated disciplines. Prospective available for remote/destination patients. In order recognized specialists from neurosurgery, neuro- ongoing annual fellowships for advanced training enhanced and intranasal delivery) and The USC BTC works cooperatively with the leadership patients will be guided through their care experience to streamline care, patients will be seen in an oncology, radiation oncology, neuro-radiology, in Neuro-Oncology and Minimally Invasive Tumor targeted/precision molecular therapies. of the affiliated hospitals (Keck Hospital of USC, both onsite and offsite via a program navigator who integrated clinic by multiple consultants during the neuro-anesthesiology, neuro-pathology, and Neurosurgery. USC Norris Cancer Hospital, the LAC+USC Medical will use a menu-based approach to individualize same initial and follow-up visits, and all cases will neuro-endocrinology. The therapeutic center will • Clinical Trials: Patient care will be driven by Center, Children 's Hospital Los Angeles, Verdugo same-day consultations, diagnostics (imaging, be discussed in a weekly multidisciplinary tumor offer the latest surgical procedures, operating room Research being a destination site for clinical trials for Hills Hospital) USC Care Medical Group, and laboratory tests, etc.), and treatment plans. board conference. technology, evidence-based medicine practices, The USC BTC research programs maximize the a variety of brain tumors. The USC BTC aims other clinical leaders in developing a high quality, clinical/translational research, and access to the potential for interdisciplinary research programs, to have 20+ investigator-initiated and national nationally ranked USC Brain Tumor Center. The focus is to treat the body as a whole and help An emphasis will be placed on genomic analysis most revolutionary clinical trials available. and in the strategic recruitment of new faculty to trials available to patients with brain tumors. our patients receive integrated medical and health of tissue, immunotherapy, precision medicine and support the aims of the center. The USC BTC will The USC BTC offers an unsurpassed concierge-style, care for an optimized outcome, including quality development of minimally invasive surgical and Conditions Treated build bridges of cooperation between Departments • Clinical outcomes: High quality outcomes, navigated experience to patients desiring top-level of life. Initial telemedicine consultations will be radio-surgical techniques. Glioma/astrocytoma, oligodendroglioma, and Institutes of the Keck School and the University imaging and genomics data will be captured brain metastases, CNS lymphoma, acoustic at large, and shares a corporate responsibility for in a prospective fashion and managed by a neuroma, meningioma, pituitary adenoma, the overall mission and success of the Keck School clinical research coordinator/data manager. SELECTED PUBLICATIONS craniopharyngioma, chordoma, and any and the University of Southern California. • Neuro-epidemiology: Collaboration with the additional CNS and skull base tumors – both Martirosian V, Chen Marín-Ramos NI, Thein Marín-Ramos NI, Jhaveri N, Marín-Ramos NI, Pérez- The USC Brain Tumor Center is a leading clinical and USC Department of Preventive Medicine TC, Lin M, Neman J. TZ, Cho HY, Swenson Thein TZ, Fayngor RA, Chen Hernández M, Tam A, Swenson malignant and benign. Medulloblastoma initia- SD, Wang W, Schönthal TC, Hofman FM. NEO212, a SD, Cho HY, Thein TZ, Hofman translational research center for a variety of brain and the California Cancer Registry will lead tion and spread: Where AH, Chen TC, Hofman FM. conjugate of temozolomide FM, Chen TC. Inhibition of to opportunities for national grants for neurodevelopment, NEO212 Inhibits Migration and perillyl alcohol, blocks motility by NEO100 through Education and spinal cord tumors, as well as development of microenvironment and and Invasion of Glioma the endothelial-to-mesen- the calpain-1/RhoA pathway. populations unique to the LA basin. cancer cross pathways. Stem Cells. Mol Cancer Ther. chymal transition in tumor- J Neurosurg. 2019 Aug 16:1-12. The Keck School of Medicine is committed to the surgical approaches/techniques. The USC BTC aims J Neurosci Res. 2016 2018 Mar;17(3):625-637. doi: associated brain endothelial doi: 10.3171/2019.5.JNS19798. goal of the highest quality educational programs to secure increased major federal (NIH, DARPA,DOD) Dec;94(12):1511-1519. doi: 10.1158/1535-7163.MCT-17- cells in glioblastoma. Cancer Epub ahead of print. PMID: • Along with USC’s medical and biotech industry 10.1002/jnr.23917. 0591. Epub 2018 Feb 13. Lett. 2019 Feb 1;442:170-180. 31419797. at every level. The USC Brain Tumor Center will be and foundational funding for Neuro-Oncology partners, the USC BTC will pioneer new a leading site for education of medical students, research, a SPORE grant designation, and a technology applications for optical Yuan E, Jarvis CA, Rutkowski M, Zada G. Buchanan IA, Min E, Deshpande K, Buchanan residents, fellows, and established providers. This significant presence at all national Neuro-Oncology Attenello FJ. Charac- Management of Pituitary Pham MH, Donoho DA, I, Martirosian V, Neman J. technology, drug delivery platforms, tumor will be accomplished through interactive medical and related subspecialty meetings. terizing Glioma Adenomas Invading Bakhsheshian J, Minneti M, Clinical Perspectives in diagnostics, robotics and novel surgical Genetics Using the Cavernous Sinus. Zada G, Giannotta SL, Hsieh Brain Metastasis. Cold student teaching sessions, industry-sponsored Cerebrospinal Fluid. Neurosurg Clin N Am. PC, Liu JC. Simulation of Dural Spring Harb Perspect Med. devices in the realm of tumor neurosurgery. Neurosurgery. 2019 Aug 2019 Oct;30(4):445-455. Repair in Minimally Invasive 2020 Jun 1;10(6):a037051. resident trainee courses, CME events, educational • Basic/Translational Science: Focus on 1;85(2):E196-E197. doi: doi: 10.1016/j.nec.2019.05.005. Spine Surgery With the Use of doi: 10.1101/cshperspect. tumor genomics/epigenetics, immunotherapy 10.1093/neuros/nyz177. Epub 2019 Jul 16. PMID: a Perfusion-Based Cadaveric a037051. PMID: 31615863; symposia, international courses for visiting faculty, PMID: 31304547. 31471051. Model. Oper Neurosurg. 2019 PMCID: PMC7263089. and expansion of simulation-based education and vaccine treatments, liquid biopsy, drug Dec 1;17(6):616-621.

82 83 NEURO-ONCOLOGY 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery keck.usc.edu/neurological-surgery/ Clinic (323) 442-5720 Academic Office (323) 409-7422 Keck School of Medicine of USC The goal of USC Neuro-oncology is to bring in innovative clinical trials that not only improve the survival of our patients but improve INSPIRATION their quality of life. Many of our trials stem from original translational research performed at USC or companies associated with USC. hen competitors line up for the American Brain Tumor Asso- Health Sciences Campus, where opportunities seemed abundant. He cold- ciation 5K Run/Walk on the University Park Campus, they called the Keck School’s Martin Weiss, MD, not knowing Weiss was a renowned know it’s for a good cause. But most will have no idea about the neurosurgeon, to plead to join a USC lab. Weiss steered the naïve but resourceful CLINICAL TRIALS AND TRANSLATIONAL RESEARCH enthusiastic scientist who helped bring the event to USC. Josh student into USC scientist Berislav Zlokovic’s group, helping propel the undergrad Neman, PhD, acknowledges he doesn’t look like the toward his doctorate in neuroscience. Olaparib in Treating Patients with Study to Evaluate Eflornithine + Lomus- An Open-Label, Phase 1/2A Dose Standard Chemotherapy vs Chemotherapy stereotypical runner. In 2016, the American Brain Tumor Advanced Glioma, Cholangiocarcinoma, or tine vs Lomustine in Recurrent Anaplastic Escalation Study of Safety and Efficacy Guided by Cancer Stem Cell Test in Recurrent Association (ABTA) awarded Neman Solid Tumors with IDH1 or IDH2 Mutations Astrocytoma (AA) Patients (STELLAR) of NEO100 in Recurrent Grade IV Glioma Glioblastoma (CSCRGBM) WHe’s not. He is just committed to This phase 2 trial studies how well Olaparib The purpose of this study is to compare the effi- NEO100-01 is a Phase 1/2A open-label study of This study will confirm the utility of chemosensitivity fighting brain tumors and helping a grant to fund research into works in treating patients with recurrent glioma, cacy and safety of eflornithine in combination with perillyl alcohol (NEO100) in patients with recurrent tumor testing on cancer stem cells (ChemoID) as a cholangiocarcinoma, or solid tumors with IDH1 Lomustine, compared to Lomustine taken alone, glioma. NEO100 is delivered four times a day by predictor of clinical response in malignant brain tumors patients in any way he can. Sometimes medulloblastoma, a tumor that primarily or IDH2 mutations. Olaparib may stop the growth in treating patients whose Anaplastic Astrocytoma intranasal administration using a nebulizer and na- such as recurrent glioblastoma and anaplastic astrocy- that means tying on running shoes, and strikes children. He immediately of tumor cells by blocking some of the enzymes has recurred/progressed after radiation and temo- sal mask for up to 6 months. There is no placebo toma. Patients with an unlimited number of recurrences needed for cell growth. ClinicalTrials.gov Identifier: zolomide chemotherapy. ClinicalTrials.gov Identifier: arm. This is the first nasal administration in the US. and multifocal disease are candidates for this study. sometimes it means studying cancer joined the ABTA’s network of scientists, NCT03212274 NCT02796261 ClinicalTrials.gov Identifier: NCT02704858 ClinicalTrials.gov Identifier: NCT03632135 cells. Neman is an Assistant Professor attending their annual conferences. of Neurological Surgery, Physiology and Away from the lab, he attended the Observation or Radiation Therapy in Stereotactic Radiosurgery (SRS) A Study of Selinexor in Combination with Trial of Enzastaurin Plus Temozolomide During Neuroscience at the Keck School of group’s Los Angeles 5K at the Fairplex Treating Patients with Newly Diagnosed Compared with Collagen Tile Standard of Care Therapy for Newly and Following Radiation Therapy in Patients in Pomona in 2017. Always looking for Grade II Meningioma That Has Been Brachytherapy Diagnosed or Recurrent Glioblastoma with Newly Diagnosed Glioblastoma with or Medicine of USC. Don’t assume he is a Completely Removed by Surgery This trial will be a randomized controlled This is a global multicenter, open-label, Without the Novel Genomic Biomarker, DGM1 surgeon, though: He holds a doctorate, opportunities, he wondered if moving (NRG-BN003) study comparing the efficacy and safety of randomized study to evaluate a combination This study will be conducted as a randomized, the event farther west to a central intraoperative radiation therapy using GammaTile regimen with or without Selinexor. The study will and his home turf is a science lab, not This randomized trial studies how well radiation double-blind, placebo-controlled, multi-center trial. versus SRS 3-4 weeks following metastatic independently evaluate 3 different combination therapy works compared with observation in Enzastaurin will be added to the standard treatment of an operating room. He works with brain Los Angeles County location could tumor resection. GammaTile is a biocompatible regimens in 3 treatment arms in participants with treatment patients with newly diagnosed grade II radiation and chemotherapy in patients with glioblasto- permanently implanted system. Each GammaTile new glioblastoma, MGMT promotor unmethylated encourage more participants. “Have meningioma that has been completely removed by ma. Patients will be evaluated for the biomarker DGM1, surgeons at the Keck School to solve unit is composed of a collagen “tile” that disease in Arm A, MGMT methylated in Arm B, surgery. Radiation therapy uses high energy x-rays which in other cancer types was shown to correlate contains 4 Cesium-131 (Cs-131) titanium- and participants with recurrent glioblastoma re- the mysteries of how healthy nerve you thought about bringing it to Los to kill the tumor cells and shrink tumors. ClinicalTri- with improved survival upon treatment with Enzastaurin. encased sources. ClinicalTrials.gov Identifier: gardless of MGMT status in Arm C. ClinicalTrials. als.gov Identifier: NCT03180268 ClinicalTrials.gov Identifier: NCT03776071 NCT04365374 gov Identifier: NCT04421378 cells and invading cancer cells in the Angeles?” he asked the organizers. brain talk to each other. When surgeons remove a tumor from a patient’s brain, they hand part of it over to Neman, a By 2018, the event was held at USC’s University Park Campus, complete with an Single Fraction Stereotactic Radiosurgery Compared Pivotal, Randomized, Open-label Study of Optune® A Phase I/II Study of Nivolumab plus or minus Ipilimumab member of the USC Norris Comprehensive Cancer Center. His lab then cultivates, appearance from members of the Trojan Marching Band. One of nine fundraising with Fractionated Stereotactic Radiosurgery in Treating Concomitant with RT & TMZ for the Treatment of Newly in Combination with Multi-Fraction Stereotactic Radio- Patients with Resected Metastatic Brain Disease Diagnosed GBM (EF-32) surgery for Recurrent High-Grade Radiation-Relapsed grows and studies its cells, trying to understand what makes them special. races for ABTA across the country, it is the only one held on a university campus. (CTSU- A071801) This study will test the effectiveness and safety of Optune® given Meningioma Ultimately, he wants to use that information against cancer. USC’s involvement has garnered the appreciation of ABTA and its CEO, This phase 3 trial studies how well single fraction stereotactic radio- concomitantly with radiation therapy (RT) and temozolomide (TMZ) This trial studies the side effects and best dose of nivolumab when giv- Ralph DeVitto. “Josh not only is the reason we’re at USC, but he also is surgery works compared with fractionated stereotactic radiosurgery in newly diagnosed GBM patients, compared to radiation therapy en together with multi-fraction stereotactic radiosurgery with or without in treating patients with cancer that has spread to the brain from and temozolomide alone. In both arms, Optune® and maintenance ipilimumab in patients with recurrent grade II-III meningioma. Immu- So what does a scientist who studies brain tumors have to do with a fundraising heading up his own fundraising team,” DeVitto said. “To have a researcher other parts of the body and has been removed by surgery. Single temozolomide are continued following radiation therapy. Optune® is a notherapy with the checkpoint inhibitors nivolumab and ipilimumab fraction stereotactic radiosurgery is a specialized radiation therapy medical device that has been approved for the treatment of recurrent - may help the immune system attack cancer, and interfere with tumor race? When you meet the effusive Neman, you understand. In a way, he’s a with that passion is so important. The work he’s doing is so challenging, that delivers a single, high dose of radiation directly to the tumor and and newly diagnosed glioblastoma (GBM) by the Food and Drug growth and spread. Stereotactic radiosurgery is a specialized radiation may cause less damage to normal tissue. Fractionated stereotactic Administration (FDA) in the United States, and Optune® has obtained therapy that delivers a single, high dose of radiation directly to the scientist-advocate. As a student at UCLA, he searched for a university lab where and he’s someone we see as a true ambassador and a true leader.” radiosurgery delivers multiple, smaller doses of radiation therapy over a CE mark in Europe for recurrent and newly diagnosed GBM. Clini- tumor and may cause less damage to normal tissue. ClinicalTrials.gov time. ClinicalTrials.gov Identifier: NCT04114981 calTrials.gov Identifier: NCT04471844 Identifier: NCT3604978 he could learn about the brain. UCLA’s labs were full, so he drove to USC’s Credit: Alicia Di Rado, USC University Communications

84 NEURO-ONCOLOGY 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery Learn more about the USC Neuro-Oncology Program at: 85 https://neuro.keckmedicine.org/treatments-services/brain-tumor-center/ Keck School of Medicine of USC CONDITIONS WE TREAT

MEDICALLY REFRACTORY EPILEPSY

TEMPORAL LOBE EPILEPSY

FOCAL CORTICAL DYSPLASIA

EPILEPSY secondary to TUBEROUS SCLEROSIS

MESIAL TEMPORAL SCLEROSIS

USC Epilepsy Care Consortium HYPOTHALAMIC HAMARTOMA

TREATMENTS WE PROVIDE

he USC Epilepsy Care Consortium is a unique partnership of The USCECC was created to serve several very important roles: RESPONSIVE NEUROSTIMULATION DEVICE six independent comprehensive epilepsy centers representing • Serve as a “living laboratory” to understand system-level barriers and VAGUS NERVE STIMULATION academic, community, public, private, adult, pediatric, urban potential solutions to optimize epilepsy care across our highly siloed and rural venues. It serves as a “living laboratory” to examine and disjointed healthcare ecosystem. STEREOTACTIC THERMOABLATION the systems level issues causing disparities in epilepsy care DEEP BRAIN STIMULATION and works to find unique and creative solutions from a “bottom- • Make available the combined resources and expertise of the Consortium TEMPORAL LOBECTOMY up patient-centered” perspective. On a practical level, it allows to patients from Central to Southern California. patients from across the age and socioeconomic spectrum to have access to SELECTIVE AMYGDALOHIPPOCAMPECTOMY • Facilitate the establishment of comprehensive epilepsy centers in theT combined resources of the all the partner centers to receive the highest critically underserved areas by allowing unprecedented resource- CORPUS CALLOSOTOMY level of epilepsy care possible while staying close to home. sharing. FOCAL CORTICAL RESECTIONS

The USC Epilepsy Care Consortium (USCECC) represents a unique effort LESIONECTOMIES It is hoped that the lessons learned by this work will inform a broader effort to understand the systems-level issues that greatly limit access to critically across the United States and world-wide to design solutions to the biggest FRONTAL LOBECTOMY needed services across our healthcare ecosystem, and to develop creative challenges in taking care of epilepsy patients. patient-centered solutions. It is the culmination of the combined efforts PARIETAL or OCCIPITAL LOBECTOMY of a large number of individuals dedicated to the concept that all epilepsy ANATOMICAL or FUNCTIONAL patients across the socio-economic and age spectra deserve access to HEMISPHERECTOMY excellent care. MULTIPLE SUBPIAL TRANSECTIONS

STEREOTACTIC RADIOTHERAPY

86 87 EPILEPSY SURGERY 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery keck.usc.edu/neurological-surgery/ Clinic (323) 442-5720 Academic Office (323) 409-7422 Keck School of Medicine of USC Public Health Dimensions of Epilepsy Solutions to Improve Health Care Delivery establish the only epilepsy center to serve adult Epilepsy is one of the most common neurological To address these issues, a group of dedicated patients in the Central Valley; the first adult disorders worldwide. Latest estimates from 2015 epilepsy specialists associated with the University admission to an EMU in the Central Valley took indicate that epilepsy affects approximately 1.2% of Southern California Keck School of Medicine place on January 2018. Additionally in 2018, Valley of all Americans, including approximately 3 million have worked to create a patient-centered ecosystem Children's Hospital, home to the first and only adults and 1/2 million children, and this number made up of independent but collaborating epilepsy epilepsy center for pediatric patients in the Central is increasing. The human impact on patients and centers linked together in a care partnership. Valley joined the Consortium. Together with the family, as well as economic impact is tremendous. adult center at Kern Medical this completes the The initial concept for a care partnership began Approximately 2/3 of all epilepsy patients are continuum of care for Central California patients with the expansion of adult and pediatric services adequately managed on medications alone. For across the age spectrum. provided at the USC Comprehensive Epilepsy the remaining “medication-resistant” patients, the Center based at Keck Hospital and LA County- How the Consortium Works American Academy of Neurology recommends that USC Medical Center. Within a few years, another The USC Epilepsy Care Consortium makes they be referred to an epilepsy center, and epilepsy epilepsy center was established at Rancho Los available the entirety of the combined expertise surgery is offered to those that meet established Amigos National Rehabilitation Center to serve found in the collaborating centers to all patients criteria. as a resource for all patients served by the Los who enter the consortium. The central goal of the Challenges in Health Care Delivery Angeles County Department of Health Services, the effort is to maximize the resources and capabilities Millions of patients who live in California have very first such center in a safety-net hospital network. of each of the partner centers to allow as much limited access to epilepsy care. While there have of the care to be delivered locally as possible. The partnership was then expanded to include the been considerable advances in the diagnostic Epilepsy surgical conferences will routinely include newly invigorated epilepsy center of Children’s and therapeutic dimensions of epilepsy care, the presentation of complex cases from each of the Hospital of Los Angeles to more broadly cover highly siloed nature of the American healthcare Consortium members either in-person or via the pediatric dimensions of the epilepsy. In 2014, ecosystem represents a tremendous challenge telemedicine, and patients move from center to key members of the USC team moved to Orange for many patients from differing socioeconomic center as necessary to take advantage of specific County to re-invigorate the epilepsy center at Hoag circumstances, resulting in glaring disparities in care resources while maintaining unprecedented Hospital, a highly resourced community hospital in and a general failure to address the public health continuity of care. An electronic data repository Newport Beach. dimensions of epilepsy. Pediatric epilepsy patients allows patient movement within the ecosystem to have the additional challenge of transitioning care as In 2017, the USC team partnered with local be analyzed to identify systems-level issues that Human hippocampal slice with multielectrode array in place for recording of local field potentials (upper left); Fiber tracking illustrating the connectivity of the hippocampal subregions using the they reach adulthood. physicians at Kern Medical in Bakersfield to limit access. 16.4 Tesla MRI (right); Ex-vivo imaging of the human hippocampus using a 16.4 Tesla MRI with associated illustration for comparison (lower left). Credit: Kristi Clark, PhD, Carol Miller, PhD, Charles Liu, MD, PhD, and Jonathan Russin, MD.

88 89 EPILEPSY SURGERY 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery keck.usc.edu/neurological-surgery/ Clinic (323) 442-5720 Academic Office (323) 409-7422 Keck School of Medicine of USC CHRISTIANNE HECK, MD, Medical Director USC Comprehensive Epilepsy Center (USCCEC) KECK HOSPITAL OF USC, LAC+USC MEDICAL CENTER and CHARLES LIU, MD, PhD, Surgical Director USC Comprehensive USC EPILEPSY CARE Epilepsy Center

CONSORTIUM CENTERS CHILDREN'S HOSPITAL LOS ANGELES LAURA KALAYJIAN, MD, Epileptologist. USCCEC. Director of EEG programs LAC-USC Medical Center

The USC Epilepsy Care GEORGE NUNE, MD, Epileptologist. USCCEC.Director of the EMU he USC Comprehensive Epilepsy Center is led by Dr. center and university. The weekly surgical conferences for Keck Medical Center Consortium (USCECC) Christi Heck, Medical Director, and Dr. Charles the consortium are held in the USC Neurorestoration Center SHAWNA BENARD, MD, Epileptologist. USCCEC represents a partnership VALLEY CHILDREN'S HOSPITAL, VISALIA Liu, Surgical Director. As part of Keck Medicine of conference room, where all the Consortium partners are JONATHAN KUO, MD, Epileptologist. USCCEC comprised of 6 individual T USC and USC Keck School of Medicine this center represents linked remotely by advanced IT facilities. ARTHUR PARTIKIAN, MD, Pediatric Neurologist. Director of comprehensive epilepsy Pediatric Neurology. LAC+USC Medical Center the academic anchor to the Consortium and is a National centers located across the JONATHAN RUSSIN, MD, Epilepsy Neurosurgeon. USCCEC & Association of Epilepsy Centers (NAEC) accredited level Children’s Hospital of Los Angeles (CHLA) is the highest LAC Medical Center southern half of California, 4 center. Since its inception, the USC Comprehensive ranked pediatric hospital in the Western USA and is a BRIAN LEE, MD, PhD, Epilepsy Neurosurgeon. USCCEC & LAC from the highly urban Medical Center Epilepsy Center has developed a unique identity of principal affiliate of the USC Keck School of Medicine. It Los Angeles and Orange KERN MEDICAL CENTER, DARRIN LEE. MD, PhD, Epilepsy Neurosurgeon. USCCEC BAKERSFIELD emphasizing access to care to all patients that span the represents the primary resource for pediatric care in the Los Counties in the South, PAUL KIM, MD, Chief of Neuroradiology. Keck Medicine of USC socio-economic spectrum in the USC-affiliated hospitals, Angeles Basin and beyond. The CHLA Epilepsy Center has and LAC+Medical Center to the mid-sized cities including LAC+USC Medical Center. This effort has led to been rejuvenated by the leadership of Dr. Deborah ALEX LERNER, MD, Neuroradiologist. Keck Medicine of USC in counties of Kern, and national recognition, with Dr. Christi Heck being selected to Holder, Medical Director, and Dr. Mark Krieger, former Chief SAMAN HAZANY, MD, Neuroradiologist. Keck Medicine of USC Fresno, to the more rural represent this concept on the National Academies Panel on of Pediatric Neurosurgery and current Surgeon-in-Chief. CAROL MCLEARY, PhD, Neuropsychologist, Keck Medicine of USC Tulare, and Kings Counties the Public Health Dimensions of Epilepsy, resulting in the The CHLA Epilepsy Center serves as the anchor pediatric LINA D’ORAZIO, PhD, Neuropsychologist, Keck Medicine of USC in Central California. Each key publication “Epilepsy Across the Spectrum”. patients within the Consortium. Dr. Holder has a record of KECIA WATARI KNOELL, PhD, Neuropsychologist, Keck Medicine of the centers represents of USC KECK HOSPITAL OF USC building successful pediatric epilepsy centers, including an example of one of NORA JIMINEZ, PhD, Neuropsychologist, LAC+USC Medical Through this center, all other Consortium centers and their at University of Pittsburgh Medical Center. Starting in Center the disparate delivery patients have access to the latest technologies and clinical 2018, and coordinated by Dr. Charles Liu, the epilepsy DEBORAH HOLDER, MD, Medical Director CHLA Epilepsy Center paradigms in the complex CHILDREN'S HOSPITAL LAC+USC MEDICAL LOS ANGELES CENTER trials related to epilepsy care, as well as all the clinical surgical services are fully integrated with that of the USC MARK KRIEGER, MD, Surgical Co-Director CHLA Epilepsy Center, American health care former Chief of Pediatric Neurosurgery, and current Surgeon in and research resources of a world-class academic medical Comprehensive Epilepsy Center. Chief CHLA ecosystem. The Consortium CHARLES LIU, MD, PhD, Surgical Co-Director CHLA Epilepsy emphasizes maximum Center resource-sharing to RANCHO LOS AMIGOS ANDY KIM, MD, Epileptologist HOAG HOSPITAL REHABILITATION CENTER allow each of the partner MATTHEW LALLAS, MD, Epileptologist centers to function beyond MICHELLE VAN HIRTIM DAS, MD, Epileptologist its capabilities as an JASON CHU, MD, Pediatric Epilepsy Neurosurgeon independent entity. JONATHAN RUSSIN, MD, Epilepsy Neurosurgeon BRIAN LEE. MD, PhD, Epilepsy Neurosurgeon

KENNETH HARTLINE, PhD, Neuropsychologist

90 91 EPILEPSY SURGERY 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery keck.usc.edu/neurological-surgery/ Clinic (323) 442-5720 Academic Office (323) 409-7422 Keck School of Medicine of USC SUSAN SHAW, MD RANCHO LOS AMIGOS NATIONAL REHABILITATION CENTER and KERN MEDICAL CENTER and VALLEY CHILDREN’S HOSPITAL HARI VEEDU, MD Medical Director Rancho Los Amigos Medical Director Kern Epilepsy Program Comprehensive Epilepsy Center HOAG HOSPITAL CHARLES LIU, MD, PhD he leadership of the USC Epilepsy Visalia California, a singular resource CHARLES LIU, MD, PhD Surgical Director Kern Epilepsy Program Surgical Director Rancho Los Amigos he Rancho Los Amigos Epilepsy Hoag Hospital is consistently Care Consortium remains between Fresno and Bakersfield. Comprehensive Epilepsy Center JOSEPH CHEN, MD, PhD Center at Rancho Los Amigos ranked highest amongst hospitals in Tacutely aware of the unique Chief of Neurosurgery Kern Medical HUI GONG, MD National Rehabilitation Orange County and is a key member challenges of providing epilepsy Valley Children’s Hospital Epileptologist. Director of Rancho Los JONATHAN RUSSIN, MD T care beyond the urban settings. In Epilepsy Center has served Epilepsy Neurosurgeon Amigos EMU Center (RLA) is led by Dr. Susan of the Consortium. The Hoag 2016, Dr. Charles Liu and Dr. Joseph a singular role in providing Shaw, Medical Director and Dr. Epilepsy Center represents BRIAN LEE, MD, PhD MICHELLE ARMACOST, MD Epilepsy Neurosurgeon Epileptologist. Director of Acute Neurology Charles Liu, Surgical Director. It an outstanding example of a Chen formed a partnership between outstanding care for the children Programs Rancho Los Amigos the USC Neurorestoration Center of Central California. Before the continues to be the only NAEC Level comprehensive epilepsy center CESAR SANTOS, MD and Kern Medical Center provide establishment of the adult epilepsy Medical Director Pediatric Neurology JONATHAN RUSSIN, MD 4 center in a safety-net hospital. based in a highly-resourced Epilepsy Neurosurgeon When it was established in 2007 by community hospital, where the sub-specialty neurosurgical services center at Kern Medical, the Valley PATRICIA CLERKIN, MD to patients in Kern County. This effort Children’s Hospital Epilepsy was Medical Director Neurosurgery BRIAN LEE. MD, PhD Dr. David Millett and Dr. Charles Liu, practice paradigm and incentives Epilepsy Neurosurgeon it was the first such center nationally differ greatly from that of academic led to the establishment of the first the only NAEC designated epilepsy MERVEEN APPU, MD and only comprehensive epilepsy center in between Sacramento Pediatric Neurologist ERICA MARTINEZ, PhD to provide comprehensive epilepsy medical centers. After leaving Neuropsychologist care to all patients irrespective Rancho Los Amigos in 2014, Dr. David center in Bakersfield and Kern County and Los Angeles. The program was RAYMOND DAVID, MD in 2017. The Kern Medical Epilepsy rejuvenated with the recruitment of Pediatric Neurologist DAVID MILLET, MD, PhD. of socio-economic status, greatly Millett became the Director of the Medical Director Hoag Epilepsy Center expanding upon the long-standing Hoag program. Concurrently in 2014, Center is led by Dr. Hari Veedu, Dr. Cesar Santos from Georgetown STEVEN EHRREICH, MD Medical Director and Dr. Charles University School of Medicine in Pediatric Neurologist CHARLES LIU, MD, PhD. efforts of the USC Comprehensive Dr. Charles Liu took leadership of Surgical Director Hoag Epilepsy Center Epilepsy Center at LAC+USC Medical the surgical aspects of the program Liu, Surgical Director. This center provides epilepsy services 2016, where he served for many years as Chief of Pediatric MELANDEE BROWN, MD Pediatric Neurosurgeon to some of the most underserved patients in California Neurology and Professor of Neurology and Pediatrics. JAMES PARK, DO. Center. It continues to exist as a close partnership between at Hoag. Almost immediately, this proven team has led the Epileptologist, Hoag Epilepsy Center RLA and LAC+USC. RLA has the only epilepsy monitoring rejuvenation of the program, with immediate escalation of and receives considerable support from the rest of the As the Medical Director of the Valley Children’s Hospital JULIA SHARMA, MD Pediatric Neurosurgeon unit (EMU) within the large network of facilities of the both medical and surgical activities. In recognition of his Consortium members. In 2018 Kern received its first NAEC Epilepsy Center, Dr. Santos has greatly increased the scope JONATHAN RUSSIN, MD Epilepsy Neurosurgeon designation, reaching Level 3. With the only adult epilepsy and quality of epilepsy services. As the only dedicated ZACHARY WRIGHT, MD Department of Health Services (DHS). leadership, Dr. Millett was the 2016 Honoree of “The Hidden Pediatric Neurosurgeon Truth, the Mind Unraveled” art exhibition. The Hoag Epilepsy monitoring unit between Sacramento and Los Angeles, the children’s hospital in Central California, Valley Children’s BRIAN LEE. MD, PhD FRED LANINGHAM, MD Epilepsy Neurosurgeon Kern Medical Epilepsy Center serves as a singular resource has established presence and partnerships in both Visalia The program was honored with a Productivity and Quality Center serves as the principal resource for epilepsy care for Radiologist Award by Los Angeles County in 2011 and continues to serve patients within the extensive St. Joseph – Hoag Health for the region, including Kern and neighboring counties and Bakersfield. In 2018, Dr. Cesar Santos and Dr. Charles VIVEK MEHTA, MD such as Tulare and Kings. Together, Dr. Richard Pantera and Liu began to create pathways for easier bidirectional access PAUL LEBBY, PhD Epilepsy Neurosurgeon as a unique resource for all patients of the Los Angeles System in Orange County. The center has achieved NAEC Neuropsychologist County Department of Health Services, the second-largest Level 3 designation almost immediately, and achieved Level Dr. Charles Liu are leading the effort to make the services to epilepsy services between Valley Children’s and Kern KAMBRIA HITTELMAN, PSYD of the Kern Medical Epilepsy Center accessible to all the Medical, as well as the other consortium centers such as KATIE ZAKI, PhD Director of Neurobehavioral Health municipal health system in the country. 4 designation in 2018. Neuropsychologist patients served by the Kaweah Delta Health Care District in Children’s Hospital of Los Angeles .

92 93 EPILEPSY SURGERY 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery keck.usc.edu/neurological-surgery/ Clinic (323) 442-5720 Academic Office (323) 409-7422 Keck School of Medicine of USC INSPIRATION

n an ordinary February day, 18-year-old Khashayar Pirouzmand was enable them to characterize what type of seizures he was having and where they breezing through the physics questions on an important exam at his originated within the brain. Jonathan Russin, MD, assistant professor of clinical high school in Iran, excited because doing well could help him get neurological surgery at the Keck School, likens the on-the-scalp video EEG to into a top university. Two hours in, without warning, his life changed “trying to listen to a conversation through a wall.” dramatically. Very suddenly, he felt a strange pressure in his brain. He raised his hand and tried to say he wanted to go outside, but couldn’t Nune and Russin escalated the testing to the next level: phase II intracranial EEG put the words together. He took a deep breath and glanced at his paper. He could monitoring to more accurately locate the area where seizures began and those O areas that are essential for speech production. This higher-level brain mapping is like no longer solve the problems he had done only minutes before. Pirouzmand left the classroom with the test unfinished. By the time he reached home a half hour later, he “being inside the room listening to the conversation,” Russin said. Russin implanted could speak again. He told his family something had happened to him, but he didn’t a very thin mesh of electrodes over the surface of the brain in the relevant region. His think it was serious. He chalked up the incident to the stressful exam. typical seizures were then recorded over the course of several days as Pirouzmand dutifully did physics homework and watched documentaries in the intensive care Little did he know that in a few years, Pirouzmand would find himself at theUSC unit (ICU). Nune then electrically stimulated the various brain areas under this mesh Comprehensive Epilepsy Center, designated a level 4 center by the National to determine which disrupted the ability to speak in his native Farsi. These would Association of Epilepsy Centers. The highest accreditation possible, this have to be preserved during surgery. Pinpointing the area responsible for language distinction indicates the center’s capability to treat the most complex as accurately as possible for each individual is essential “because once patients cases. Within the USC Comprehensive Epilepsy Center, a multidisciplinary medical have been having seizures for so long, their brain often has reorganized itself,” Russin team provides the most advanced care for patients with complex issues, including noted. Armed with the results, Russin could proceed. His goal was to remove as much those who experience uncontrolled seizures, severe side effects from medication of Pirouzmand’s tumor as possible, while avoiding delicate tissue. or who want to get pregnant while having epilepsy. The team includes board- certified epileptologists, neurosurgeons, neuroradiologists and psychologists, “You’re talking about potentially curing somebody of their seizures and along with epilepsy nurses, occupational therapists and nutritionists. More people changing the trajectory of their life,” he said. “If our patients have the courage die of epilepsy (50,000) each year than from breast cancer (40,000). This to undergo these procedures, it’s our responsibility to do the job right with the least includes people who develop SUDEP or “sudden unexpected death in epilepsy”. amount of risk.” Pirouzmand was more than ready. “I said, ‘Let’s go.’ This was my Pirouzmand initially met with George Nune, MD, assistant professor of clinical chance to get better.” For Pirouzmand, surgery gave him his life back. He occasionally neurology at the Keck School. “Approximately one-third of patients have hears a high tone in his ear (an “aura” or warning of a potential seizure), but the medically refractory epilepsy, which can’t be controlled with medication,” seizures no longer come. He is on two medications for now, a precaution for the first Nune said. Nune asked Pirouzmand if he was interested in surgery, which held the few years after surgery. potential to remove the source of his epileptic seizures. Pirouzmand has started driving again and he is hard at work studying for his university The first step: capturing the electrical impulses in Pirouzmand’s brain. The degree. During his treatment at Keck Hospital, he realized the specific field he wants center is equipped with the most advanced imaging and diagnostic technologies, to pursue — electrical engineering. Being in the hospital, with electrodes implanted including video electroencephalographic monitoring (EEG), an invaluable tool to in his brain, he felt like a living, breathing embodiment of science at its best. “In one diagnose epilepsy symptoms, using non-invasive electrodes attached to the head. moment, engineering and neuroscience and medical school were all combining Pirouzmand spent a week in Keck Hospital of USC, as his medical team gradually to cure the patient — me — of epilepsy,” Pirouzmand said. “It’s kind of amazing.” withdrew him from all medication to trigger and track his seizures. This would Credit: Candace Pearson, USC News

94 EPILEPSY SURGERY 2020 - 2021 ANNUAL REPORT USC Department of Neurological Surgery Learn more about the USC Epilepsy Care Consortium at: 95 https://epilepsycareconsortium.usc.edu Keck School of Medicine of USC USC DEPARTMENT OF NEUROLOGICAL SURGERY DEVELOPMENT Please join us in the effort to help change the future of health sciences in a positive direction through support of the Department of Neurological Surgery. The Department of Neurological Surgery offers numerous high impact funding opportunities for philanthropists that are interested in supporting one of the most respected and creative teams in the country.

Established in 1919, the Department of Neurological Surgery is poised for continued break-through results under the dynamic leadership of Dr. Steven Giannotta and uniquely talented clinical faculty, researchers, and multidisciplinary staff that work together at Keck Medicine every day.

Under the Keck Medicine Initiative, the Department of Neurological Surgery fundraising priorities include:

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Brian Loew, MPA Senior Director of Development – Neurosciences [email protected] (213) 308-4764 USC DEPARTMENT OF NEUROLOGICAL SURGERY Keck School of Medicine of USC 1200 North State Street, Suite 3300 LAC+USC Medical Center Los Angeles, California 90033 www.keck.usc.edu/neurological-surgery/