University of Pennsylvania Health System

Bench, Bedside and Beyond

The Penn Medicine Neuroscience Center (PMNC) is dedicated to the advancement of the understanding of the brain, spine and peripheral nervous system.

Built on the foundations of the philosophy, “Bench, Bedside and Beyond,” the multidisciplinary PMNC facilitates and strengthens the integration of Penn’s neuroscience programs within the areas of clinical care, research and education. This publication will highlight the exciting, collaborative work of the clinical specialists, basic science and clinical researchers, and educators who are part of Penn’s world-class neuroscience programs.

Saturday, May 8, 2010

Revolutionary Minimally-invasive Surgical Approach Pioneered by Penn Cleared by the FDA


TransOral Robotic Surgery (TORS), the revolutionary, minimally-invasive robotic surgery technique developed by head and neck surgeons at Penn Medicine has been cleared by the U.S. Food and Drug Administration (FDA).

TORS is the world’s first group of minimally-invasive, transoral otolaryngologic surgical procedures to treat benign tumors and select malignant tumors of the mouth and throat in adults. Utilizing the daVinci® Surgical System (Intuitive Surgical, Inc., Sunnyvale California), this landmark breakthrough results in shorter, virtually scarless head and neck surgery. Designed to avoid incisions for primary site resection, TORS is performed through the patient’s mouth and provides unprecedented access to the small and often difficult-to-reach areas of the mouth and throat.

An Historic Legacy
Bert W. O’Malley, Jr., MD, Gabriel Tucker Professor and Chairman, and Gregory S. Weinstein, MD, Professor and Vice Chair of Penn Medicine’s Department of Otorhinolaryngology – Head and Neck Surgery, are pioneers in the field of robotic surgery. In 2004, they founded the world’s first TransOral Robotic Surgery (TORS) program at Penn, where they developed and researched the TORS approach for a variety of robotic surgical approaches for both malignant and benign tumors of the mouth, voice box, tonsil, tongue and other parts of the throat. Drs. O’Malley and Weinstein invented the TORS technique, and have performed more TransOral Robotic Surgery (TORS) procedures than any other physicians in the world.

Revolutionizing and Redefining the Treatment of Head and Neck Cancer
Since 2005, approximately 370 Penn Medicine patients have participated in the world’s first prospective clinical trials of TORS. These research trials comprise the largest and most comprehensive studies of the technology on record. “TORS has dramatically improved the way we treat head and neck cancer patients, completely removing tumors while preserving speech, swallowing, and other key quality of life issues,” said Dr. O’Malley.

The standard surgical and non-surgical approaches to the management of laryngeal, hypopharyngeal and oropharyngeal cancers, while in many ways successful, had significant limitations. Head and neck tumor treatments often involve a combination of surgery, radiation therapy, and chemotherapy. In many cases, surgery offers the greatest chance of cure; yet conventional surgery may require an almost ear-to-ear incision across the throat or splitting the jaw, resulting in speech and swallowing deficits for patients.

In comparison, TORS outcomes are markedly improved when compared to standard chemotherapy, radiation or traditional open surgical approaches for oropharyngeal cancer. When compared to traditional surgeries, after their cancers have been removed successfully, patients have been able to begin swallowing on their own sooner and leave the hospital earlier.

Additional benefits to patients that undergo transoral robotic surgery (TORS) can include shorter hospitalization, a quicker return to normal activity, fewer complications compared to traditional open surgery, less scarring than traditional open surgery, less risk of blood transfusion when compared to open surgery, and no routine use of tracheostomy during surgery compared to routine use for open surgery.

“Based on our data and patient outcomes, coupled with the national and international enthusiasm and interest for TORS, we are changing the way oropharyngeal cancer and tumors will be treated now and in years to come,” noted Dr. Weinstein. “We are already investigating new TORS treatments for other conditions such as sleep apnea, and collaborating with colleagues in Penn Neurosurgery to use TORS to remove skull base tumors and repair cervical spine disease.”

Teaching the Teachers
The TORS program benefits not only patients seeking state-of-the-art care, but also physicians who come from around the world to observe and learn about this groundbreaking procedure. Drs. Weinstein and O’Malley created the first and only training program in TransOral Robotic Surgery (TORS) in the world. They have trained numerous surgical teams from 12 different countries, many of whom have started TORS programs at their respective institutions. With the FDA approval (December, 2009) of the daVinci System for transoral otolaryngology, Penn Medicine has expanded its well-established training program to include surgical teams from the United States.

“It is very exciting that a concept conceived at Penn, evaluated in pre-clinical experimental models at Penn, tested in clinical trials at Penn, and then taught to key surgeons and institutions both within the US and internationally has been officially recognized by our federal governing agencies and peers around the world as a new and improved therapy for select neck cancers and all benign tumors,” Dr. O’Malley concluded.

For more information about the Penn TORS Program, please visit pennmedicine.org/ent or call 800-789-PENN.

45,000 Americans and approximately 500,000 people worldwide are diagnosed with head and neck cancers each year.

Penn Neurosurgeons Advance Spine Care Giving Hope to Patients and Yielding Improved Results and Proven Success

Penn Neurosurgery is a regional and national leader in providing quality spine care utilizing a multidisciplinary team approach, and implementing the latest advances in techniques and technology.

One of the hallmarks of Penn’s acclaimed spinal surgery program is the personalized treatment plan each patient receives. No matter the condition or problem, Penn Medicine neurosurgeons possess a vast arsenal of tools to evaluate, diagnose and treat the most complex disorders of the spine.

Sophisticated Diagnostic Techniques
Penn specialists are backed by the most extensive neurodiagnostic and imaging facilities in the region. Patients are diagnosed utilizing the latest neuroradiological and electrodiagnostic techniques including high resolution MRI scanners, CT myelography, EMG and discography, and electrophysiological testing.

Comprehensive Spine Care Team
A targeted treatment plan is developed for each patient by a specialized team led by five neurosurgeons, in addition to neurologists, rheumatologists, oncologists, orthopaedists, rehabilitation specialists, physical therapists, radiologists, and pain management specialists. This extensive and collaborative team approach to spine care ensures a thorough consideration of both surgical and non-surgical treatment of pain and neurological symptoms.

The Highest Quality Treatment with the Best Outcomes Possible
Conditions treated cover all aspects of spine disorders including degenerative disease (disc herniations, neck and back pain, spinal stenosis), spinal tumors and spinal trauma.

Penn physicians strive to discover new ways and new devices to improve patient outcomes. Treatments and procedures available include decompression (discectomy and laminectomy); fusion (cervical, thoracic and lumbrosacral) as well as artificial disc technology and motion sparing procedures.

“The neurosurgical spine program is continuing to advance and become even more comprehensive,” said William C. Welch, MD, FACS, FICS, Professor and Vice Chair of Neurosurgery and Chief of Service at Pennsylvania Hospital. “We are performing cutting-edge treatments that have never been done here before.” Penn neurosurgeons are continually working to find new methods and devices to improve patient outcomes, integrating the latest technologies and cutting-edge surgical techniques including robotic surgery and minimally-invasive treatments as well as surgical devices such as the ultrasonic bone cutter and CO2 laser.

Research efforts go hand-in-hand with patient care at Penn Medicine, where clinicians and researchers are applying basic science and clinical research to improve patient care. The Penn Neurosurgical Spine Center has increased research efforts in the lab. There is a new biomechanical research laboratory at Pennsylvania Hospital where new spinal devices and techniques are being tested and studies are performed to increase the fundamental understanding of spine physiology.

Award-Winning Innovation
Independence Blue Cross has designated the Hospital of the University of Pennsylvania and Pennsylvania Hospital as Blue Distinction Centers® for Spine Surgery. Blue Distinction is a designation awarded by the Blue Cross and Blue Shield companies to medical facilities that have demonstrated expertise in delivering quality healthcare for spine surgery.

Penn Medicine continues to be the choice for complex conditions of the spine. For more information, visit PennMedicine.org or call 800-789-PENN.

The Penn Multiple Sclerosis Center — Setting the Standard for Comprehensive MS Care in the Region


The Multiple Sclerosis (MS) Program at Penn Medicine provides comprehensive evaluation, diagnosis and treatment for patients with MS and other demyelinating disorders of the central nervous system. In addition to maintaining the highest standards for clinical service, the Penn MS program is a leader in MS training and in clinical and laboratory-based research.

The Penn MS Program provides consultative services and ongoing care for more than 3,000 patients yearly. The program includes eight full-time faculty members and specializes in quality, state-of-the-art clinical care with a personal approach. Patients are evaluated by a multidisciplinary team that includes physicians and highly-trained nurse practitioners who are experts in symptom management, treatment, patient education, health maintenance and general well-being for patients with MS.

Individualized Clinical Evaluation, Diagnosis, Treatment and Support
Neuroradiologists at Penn are developing new MRI technologies that enhance the diagnosis of MS and the assessment of disease activity. Cutting-edge imaging protocols and techniques including the use of 3-Tesla magnets have been implemented through collaborative efforts of Penn’s MS researchers and radiologists for use in MS trials as well as in clinical care.

The Penn MS Center’s team meets regularly at case conferences. A comprehensive, multidisciplinary approach is employed, involving regular consultations with departments including rehabilitation medicine, physical and occupational therapy, urology, neuropsychology, and ophthalmology.

Additional patient support is key to helping patients manage their treatment and the potential side effects. Nurse practitioners and MS-certified nurses provide individualized training and support for symptom management; physical therapy is available where appropriate; and support groups organized by MS Center staff offer opportunities for patient education and support.

Research — Shaping the Future of MS Treatment
Penn MS Center researchers lead clinical and laboratory-based research programs that are recognized at both regional and international levels for their contributions to the advancement of MS treatment. Research projects are sponsored by organizations including the National Institutes of Health, the National MS Society and industry.

As active and consistent participants in pivotal MS treatment trials, faculty and staff in the MS program have provided important contributions to the development of immunomodulatory and other forms of therapy. Neuroradiology and immunology research at Penn is continuing to advance techniques and models of disease to advance diagnosis and treatment. Other research efforts are studying the genetic aspects of MS to determine which patients are at most risk of progressing and who might benefit from specific therapy.

The MS Center is the international epicenter of vision research in MS. Current collaborative studies with Johns Hopkins University and UT Southwestern in Dallas are underway to determine which visual function tests and ocular imaging (OCT) measures best detect MS-related visual symptoms and provide the best markers for gauging the effectiveness of MS therapies.

“This is an exciting time in the field,” remarked Laura Balcer, MD, MSCE, Professor of Neurology, Ophthalmology, and Epidemiology and Chief of the Penn MS Division. “Research being developed at Penn is leading to new treatment options for patients with MS. Every step we take brings us closer to effectively targeting the mechanisms by which MS causes disability,” Dr. Balcer concluded.

From Bench to Bedside – A Spotlight on Research – Neurodevelopmental Genomics: Trajectories of Complex Phenotypes

Many mental illnesses are common disorders that emerge during childhood and adolescence and may continue into adulthood, often with debilitating results. In order to prevent these consequences it is important to identify early risk factors and manifestations of these conditions.

A collaborative research effort between the Brain Behavior Laboratory at the University of Pennsylvania and the Center for Applied Genomics at the Children’s Hospital of Philadelphia (CHOP) is focusing on articulating how these factors contribute to shaping the development of brain systems that underlie complex behavior.

The research study is led by renowned researchers and clinicians Raquel E. Gur, MD, PhD at the University of Pennsylvania and Hakon Hakonarson, MD, PhD at the Children’s Hospital of Philadelphia.

Within the past three years, children who presented to CHOP for various reasons, including both sick visits and well visits, were genotyped. In the Fall of 2009, as part of the American Recovery and Reinvestment (ARRA) stimulus grants, the aforementioned Penn and CHOP researchers received grant funding to phenotype 10,000 children and adolescents between the ages of eight to twenty-one from the Philadelphia region. They were able to draw from the data set that had already been genotyped at CHOP. This group of children and adolescents and their families had already agreed to be contacted for further research.

The grant’s main focus is to phenotype or characterize the children and adolescents who have already been genotyped from the perspective of brain and behavior. All children and their parents who consented to the study provided a blood sample for DNA and genotype, and gave their permission to be followed for the duration of the study. They will be assessed for behavioral dimensions indicating vulnerability to major mental illnesses. The assessment will include measures of key features including attention deficit, anxiety, mood, psychosis proneness and substance abuse as well as measures of cognitive and emotion processing.

Researchers are administering a computerized neurocognitive battery of tests to the 10,000 individuals. Following this, 1,000 of these children will return for MRI studies. The results of this random sample will be added to the brain behavior measures and genetic information. The imaging performed includes functional MRI, structural MRI, and diffusion tensor imaging (DTI).

Comprehensive research such as this can build an unprecedented information infrastructure that combines genomics and brain behavior measures and will enable follow-up of subsamples of children with different disorders. This rich data set will not only enable researchers to learn a lot about brain behavior and how it interacts with genetic factors, it will also enable researchers to gather information from subsets of both typically-developing children as well as those children with brain disorders. The information can be used for more in-depth research and also offers the opportunity to develop new treatments.

For example, researchers may be able to identify which genes contribute to the brain system that regulates attention — both normal attention, and disrupted attention in children with disorders of attention
like ADHD.

In addition to the EMR (electronic medical records) that are available, the researchers are also conducting direct evaluations that cover healthy development and major neuropsychiatric disorders that emerge in childhood. Testing covers questions about personal history, education, and social measures, in addition to computerized neurocognitive testing that measures attention, memory, language, mental flexibility, spatial skills, and emotion processing.

A staff of more than 40 people have been hired to assist in conducting the study, including psychometricians, as well as experts in genomics, bioinformatics, and imaging. This two-year study began in October 2009 and runs through August 2011.

This rich data set will not only enable researchers to learn a lot about brain behavior and how it interacts with genetic factors, it will also enable researchers to gather information from subsets of both typically-developing children as well as those children with brain disorders.

New Hope for Patients with Addiction

Penn Medicine’s Charles O’Brien Center for Addiction Treatment is an outpatient facility offering state-of-the-art addiction treatment provided by nationally-renowned experts in the field. Named for Dr. Charles O’Brien, one of the preeminent addiction researchers in the world, the Center offers treatment for all addictive substances, including alcohol, cocaine, heroin, pain killers, and marijuana.

As part of Penn Behavioral Health, the Charles O’Brien Center is dedicated to providing the highest quality of addiction treatment. At their first visit to the Charles O’Brien Center for Addiction Treatment, new patients receive a comprehensive evaluation of their addictive behaviors and their global physical and mental health. Family members are encouraged to participate in the initial evaluation and, when appropriate, ongoing education and treatment. Following the evaluation, the team develops an individualized plan for patients and their families.

Treatment fully integrates the psychological and biological interventions that are most likely to lead to sustained recovery, including pharmacological treatments, as well as individual, family and group therapy. In addition, if needed, treatment of addiction can be coordinated with treatment of anxiety, depression, or other mental health concerns.

As an added benefit, physicians at Penn are on the cutting-edge of medical research and involved in clinical trials, allowing them to have access to breakthrough medications that are becoming available and could make a difference in patient recovery. When patients have achieved their treatment goals and are ready to discontinue regular treatment at the Charles O’Brien Center, the treatment team works with them to design a plan for sustaining their success.

The Charles O’Brien Center for Addiction Treatment provides individualized addiction treatment with sustained results. For information on how to refer a patient or to schedule an appointment, call (215)222-3200, ext. 106, or visit the website at www.med.upenn.edu/addiction.

When patients have achieved their treatment goals and are ready to discontinue regular treatment at the Charles O’Brien Center, the treatment team works with them to design a plan for sustaining their success.

Friday, November 20, 2009

Stimulus-Funded Research Grants

Research is one of the cornerstones of the Penn Medicine Neuroscience Center, aiding in its mission to bolster the practice of translational medicine. Faculty from throughout the University of Pennsylvania as a whole submitted grant applications to institutions such as the National Institutes of Health and the National Science Foundation. In response, the American Recovery and Reinvestment Act (ARRA) has awarded more than $30 million total in research funding to Penn.

The importance of the neurosciences as a national health priority is evidenced by the fact that departments from throughout the Penn Medicine Neuroscience Center (PMNC) were awarded almost half of that total figure, more than $14 million in recent stimulus-funded research grants.

As of August, 2009, PMNC departments were awarded 24 grants as part of the ARRA funding program. Departments included Anesthesiology, Neurology, Neuroscience, Neurosurgery, Otorhinolaryngology—Head and Neck Surgery, Pathology and Laboratory Medicine, and Psychiatry.

Some of the grants highlighted include:

Murray Grossman, MD, Associate Professor of Neurology, received a grant from the National Institute on Aging/NIH/DHHS to study Conceptual Processing in Alzheimer’s disease. This work will improve the understanding of the cognitive and neural basis for semantic memory, lead to improved diagnostic accuracy in Alzheimer’s disease, and suggest several potential avenues for improving the quality of life in these patients.

M. Sean Grady, MD, Charles Harrison Frazier Professor and Chairman, Department of Neurosurgery, received a grant from the National Institutes of Health to study the Functional Reorganization of Limbic Circuitry After Traumatic Brain Injury. Traumatic brain injury (TBI) is the leading cause of death and disability in children and young adults. Despite initial cognitive deficits, many individuals experience significant recovery. This study investigates how the ability to learn and recall information recovers. The compensatory mechanisms demonstrated in the contralateral hippocampus may lead to a better understanding of cognitive recovery in human TBI and lead to novel strategies for improving speed and extent of recovery.

Brian M. Salzberg, PhD, Professor of Neuroscience and Physiology, was awarded a grant from the National Institutes of Health for an Optical Study of Secretion in Mammalian Nerve Terminals. Secretion is central to diverse biological functions such as information processing, reproduction, motility, temperature regulation, metabolism, the immune response, and signal transduction. However, the full elucidation of its mechanism(s) remains a challenge to cell physiologists. This study seeks to identify some of the cellular events that define calcium-dependent excitation coupling in mammalian peptidergic nerve terminals.

Barry L. Ziober, PhD, Adjunct Associate Professor of Otorhinolaryngology–Head and Neck Surgery received a grant from the National Institutes of Health to study the Molecular Analysis of OSCC Tumor Invasion. In addition to identifying the best signature for prediction of osee nodal disease, the results from this study will identify genes, biomarkers and signaling pathways in the tumor microenvironment that can be targeted for diagnostic, prognostic and therapeutic studies. The lymph node metastasis gene signature identified will have a profound clinical utility for reducing osee patient mortality and morbidity.

Youhai H. Chen, MD, PhD, Associate Professor of Pathology and Laboratory Medicine was awarded a grant from the National Institutes of Health for his research on Autoimmune Encephalomyelitis and C-REL. Multiple sclerosis (MS) afflicts more than 300,000 people in the United States alone. Through enhanced understanding of how a specific transcriptional regulator mediates autoimmune encephalomyelitis, this work aims to not only help elucidate the pathogenic mechanisms of multiple sclerosis but also aid in developing specific strategies to treat or prevent the disease.

Anna R. Childress, PhD, Research Associate Professor of Psychology in Psychiatry received a grant to study the Extinction of Limbic Activation to “Unseen” Cocaine Cues from the National Institutes of Health. Cocaine patients show a remarkable persistence of desire and arousal to cocaine cues, months or even years after the last dose of the drug. These “extinction-resistant” responses may be due to cocaine patients’ documented (structural and functional) deficits in the prefrontal cortex (PFC) — a region necessary for modulating the downstream limbic (“GO!”) regions — and for the new learning that underlies extinction. This study tests whether extinction of the brain response to cocaine cues can occur outside awareness, and whether extinction can be facilitated by the partial agonist varenicline.

The Penn Medicine Neuroscience Center is dedicated to the advancement of the understanding of the brain, spine and peripheral nervous system. Grants such as those referenced above are continuing to foster the PMNC’s critical “Bench to Bedside” mission.

At Penn, the schools, centers, and institutes across the campus are brought together in the PMNC to create an integrated approach to patient care, education and research. Thus, the ground-breaking discoveries and research being launched with these studies will ultimately lead to advances in clinical care for these patients.

Penn Neurovascular Center Treatment for Cerebral Aneurysms

The Penn Neurovascular program is the only comprehensive cerebrovascular and endovascular center in the Philadelphia region and is one of only a few in the United States. The Center is a nationally-recognized primary referral center for the treatment of aneurysms, arteriovenous malformations (AVMs), arteriovenous fistulas (AVFs), strokes and TIA’s, carotid artery and vertebral artery atherosclerotic disease (hardening of the arteries), intracranial stenosis as well as other conditions such as cavernous malformations and Moyamoya disease.

Penn’s world-renowned multidisciplinary team of neurovascular specialists, backed by the most extensive neurodiagnostic and imaging facilities in the region, perform more than 2000 procedures each year involving the most complex neurological disorders. Each patient’s case is discussed at a weekly Neurovascular conference where a personalized treatment plan is developed based on the patient’s specific needs. Center physicians work closely with referring physicians and provide a rapid and thorough evaluation of patients with all types of neurovascular disorders.

A complete, highly specialized array of services is available, from diagnosis, treatment and outpatient consultations to access to Penn’s brand new NeuroIntensive Care Unit. A Level I Trauma Center and Acute Brain Injury Center, Penn’s NeuroIntensive Care Unit is the most technologically advanced and sophisticated neuro-critical care unit on the eastern seaboard and the only academic facility of its kind in the region.

One Phone Call for allNeuroemergency Transfers
Penn’s Neuroemergency Transfer Policy is simple, seamless, and takes only one phone call. Calls to the PennTransfer Center about any neuroemergency are immediately transferred to the attending neurosurgeon or neurologist on duty. Working directly with the attending physician, the Transfer Center handles all transportation to the Hospital of the University of Pennsylvania or Pennsylvania Hospital as well as all other details, including bed assignment in the NeuroIntensive Care Unit.

For transfers of all patients with acute neuroemergencies, please call the Penn Transfer Center directly at (215) 662-3555.

Diagnostic and Treatment Resources
State-of-the-art diagnostic tools include computed tomography (CT) scan; Spiral CT, 3D CT-angiography, magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), MR-spectroscopy, cerebral angiography, biplane angiography, 3-D rotational angiography and Xenon CT, SPECT and PET scanning.

The Center employs the latest treatment modalities, including microsurgery (skull-base surgery; neurovascular surgery; and aneurysm clipping) as well as endovascular surgery such as coiling, stenting, angioplasty, and embolization.

Penn neurosurgeons are applying minimally-invasive endovascular technology to the treatment of cerebral aneurysms. Endovascular coiling is a technique developed as a safer alternative to surgical clipping that does not involve open cranial surgery and is typically performed in less time with quicker recovery. Analysis has determined that endovascular coiling is associated with a lower risk of new symptoms or disability after treatment, shorter hospital stays and shorter recovery times compared with surgery. More recently, physicians of the Neurovascular Center have begun to use a copolymer, embolic material, or glue, to treat cerebral aneurysms. This material produces total or near-total filling of the aneurysm and allows excellent aneurysm neck and parent vessel reconstruction.

“Patients are benefiting from this new technology,” said Michael F. Stiefel, MD, PhD. In fact, the only evidence of an endovascular procedure afterward is a small scar in the leg. “Patients have better outcomes, shorter hospital stays, and quicker recoveries,” continued Dr. Stiefel.