Innovate Neurology & Neurosurgery: Summer 2013 by Barnes Jewish

NEUROLOGY & NEUROSURGERY

Summer 2013

/ COVER STORY /

Advances in Brain Tumor Therapies

/ F E AT U R E /

New Treatments for Multiple Sclerosis

A L S O i n th is iss ue :

• Stereotactic laser ablation offers surgery for inoperable brain tumors • First Alzheimer’s prevention trials launched • Targeting pituitary tumors • Current clinical trials

C OVE R STO RY

W r i t t e n b y J I M G O O D W IN

Neurology & Neurosurgery

Summer 2013

In This Issue FEATURES

Cover Story Advances in Brain Tumor Therapies

New Treatments for Multiple Sclerosis NEWS

Stereotactic Laser Ablation Offers Surgery for Inoperable Brain Tumors

Trigeminal Neuralgia: Matching Treatment to Patient

Stroke Patients Benefit from Carmaker’s Efficiency

First Alzheimer’s Prevention Trials Launched

Targeting Pituitary Tumors

Neurofibromatosis 1 and Learning Disorders

NFL Funds Study of the Brain After Concussions

Leadership: Neurology and Neurosurgery

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AWARDS AND HONORS CLINICAL TRIALS

Human glioblastoma cells in culture: The markers for tumors, or nestins, are green; the nuclei are blue.

ADVANCES IN BRAIN TUMOR THERAPIES

Image courtesy of Albert Kim, MD, PhD

Surgery remains a mainstay treatment for brain tumors, but advances in technology and new clinical trials mean patients have more treatment options— some noninvasive—and quicker recoveries. Neurosurgeon Albert Kim, MD, PhD, and colleagues are advancing the treatment of brain tumors through a number of clinical trials, including ones looking at brain tumor vaccines and genome sequencing.

Albert Kim, MD, PhD

“We have to attack brain cancer from all sides using different approaches,” says Albert Kim, MD, PhD, a Washington University neurosurgeon at Barnes-Jewish Hospital and the Alvin J. Siteman Cancer Center. “That’s going to be the most effective strategy, and that’s what we offer here.” Physicians in the department of neurosurgery employ neuronavigation endoscopy, or brain GPS, for minimally invasive surgeries and other advanced tools. They’re also developing and using next-generation brain tumor technology, including: n Improved brain mapping that allows neurosurgeons to monitor and protect critical brain areas while a patient is anesthetized. Older technology allowed mapping only during awake craniotomies. n Intraoperative MRI, which allows surgeons to identify diseased brain tissue before surgery is completed.

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Early data shows that patients with a glioblastoma who receive a vaccine and standard therapy live twice as long as those who receive only standard therapy.

F E ATU RE STO RY

Washington University neurosurgeons also use an MRI-guided laser treatment that can reach deep-seated tumors traditionally thought to be inoperable and achieve successful outcomes. The procedure is especially helpful for patients with medical comorbidities that make open surgery too risky. It also improves the effectiveness of chemotherapy on brain tumors, says David Tran, MD, PhD, a Washington University neuro-oncologist at Siteman.

Ongoing clinical trials at the Siteman Cancer Center will examine the effectiveness of brain tumor vaccines. “By heating up the tumor using this device, you can also disrupt the blood-brain barrier,” he says. “So we’re using the device to achieve cytoreduction but also to increase delivery of chemotherapy.” A clinical trial will further study the technology. Other ongoing clinical trials at Siteman are examining the effectiveness of brain tumor vaccines. One strategy calls for collecting fresh tumor tissue in the operating room and processing it in the lab. Next, researchers collect dendritic cells from a patient and activate them ex vivo before they are reinfused into the patient in

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the form of a vaccine. A similar approach, currently available only at Siteman and a few other major cancer centers, is being used to develop personalized vaccines that use T cells rather than dendritic cells. Another type David Tran, MD, PhD of vaccine targets a genetic mutation unique to glioblastoma, the most common high-grade brain cancer and the most aggressive. Early data shows that patients who received the vaccine in addition to the current standard therapy live more than twice as long as patients who received standard therapy alone. The adverse side effects were, in most cases, no worse than those of a flu vaccine, Tran says. Genome sequencing offers another step forward. By studying a patient’s DNA, researchers are learning which mutations predict response to a particular drug. Such advances, whether in genomics, technology or basic science, could ultimately mean more treatment options and better outcomes, Kim says. “Parts of the tumor cannot be treated with surgery, and we have to tackle them using other means.” n

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New Treatments for Multiple

ashington University neurologist Anne Cross, MD, remembers a very different world when she first began treating patients with multiple sclerosis (MS) almost three decades ago. “It’s incredible—the MS Center has changed so much,” says Cross, director of the John L. Trotter Multiple Sclerosis Center at Barnes-Jewish Hospital. “During the first 10 years, we had no treatments that were effective at slowing multiple sclerosis. Now we have an array of treatments either already in use, in clinical trials or on their way soon. There are so many new options opening up.”

Sclerosis Written by MICHAEL PURDY

Physicians normally group patients into one of four clinical subtypes to help anticipate the effects of MS and which medications may work: relapsing remitting, secondary progressive, primary progressive and progressive relapsing. However, the unpredictability of MS continues to frustrate. The way patients respond to the new treatments, which have varied mechanisms of action, may provide scientists with a much more accurate sense of what’s going wrong in the different forms of MS and in individual patients. That knowledge could lead to better, more targeted treatment and improved prognosis.

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the brain and spinal cord,” Cross says. “We think that may be helpful in MS because fingolimod can bind to SIP receptors in the brain, which leads to an increase in neurotrophic factors, at least in mice.” Fingolimod is now available at the MS Center as a treatment for relapsing forms of MS.

The illustration on the left represents a normal myelin sheath; the one on the right, a damaged sheath from a patient with multiple sclerosis.

Emerging Solutions

Anne Cross, MD, is clinical director of the John L. Trotter Multiple Sclerosis Center at Barnes-Jewish Hospital. She also is principal investigator of ORATORIO, a trial that is testing whether ocrelizumab will slow or stop neurologic progression in patients with primary progressive MS.

Current Standard of Care

Newest Options

Current medications offer some benefit for certain MS patients but fall short of controlling the disease. For relapsing remitting MS, the most common form, doctors often prescribe beta-interferons or glatiramer acetate. But they must be taken as injections and can cause adverse side effects, including injection-site reactions and a flu-like illness. These factors may explain why up to 50 percent of MS patients treated with the drugs fail to regularly take their injections. Additional oral medications are becoming available for relapsing MS patients; they reduce the relapse rate by about 30 percent to 50 percent, but there is controversy over their ability to reduce long-term disability. For secondary progressive MS and primary progressive MS, no treatments have proved to be effective at reducing progressive disability.

The latest MS pharmaceutical treatment approved by the FDA is teriflunomide, a compound that blocks rapid white blood cell proliferation—a key component of the autoimmune processes that cause MS. Teriflunomide is among the first MS drugs that can be administered orally via a daily tablet. Another daily tablet, fingolimod, won FDA approval in 2010. It traps immune lymphocytes that contribute to MS inside the lymph glands where they develop and is effective for relapsing forms of MS. A multicenter trial called INFORM is ongoing to study whether fingolimod will also be effective as a treatment for primary progressive MS. Neurologist Becky Parks, MD, co-director of the MS Center, is leading that study at Washington University and Barnes-Jewish Hospital. “There’s also evidence that fingolimod crosses the blood-brain barrier and enters

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In addition to the INFORM trial, Washington University neurologists at the center are currently participating in three clinical trials of new monoclonal antibodies designed for MS treatment. n Robert Naismith, MD, is leading OPERA, an assessment of the benefits and risks of treating relapsing remitting patients with a beta-interferon versus ocrelizumab, an antibody that depletes immune B cells. n Anne Cross, MD, is principal investigator for a second ocrelizumab trial, ORATORIO. This study is testing whether ocrelizumab will slow or stop neurologic progression in patients with primary progressive MS. n Becky Parks, MD, is leading the center’s study of daclizumab, an antibody that increases CD56+ natural killer T cells. Striving for Tailored Treatment

Cross notes that the alterations some of the newest MS treatments cause in the immune system could produce vulnerability to infection. She says physicians have to strike a careful balance between the benefits of new MS treatments and potential risks, some of which are not yet well-characterized.

“The challenging aspect of having all these new drugs is that now we have a lot of different options to weigh,” Cross says. “We desperately need ways to determine which patients will do better on which drugs to help with these clinical decisions.” To meet this need, Cross and colleagues Sheng-Kwei Song, PhD, and Dmitriy Yablonskiy, PhD, are developing new imaging techniques to better characterize what happens in the brains of MS patients before, during and after treatment.

“The challenging aspect of having all these new drugs is that now we have a lot of different options to weigh,” Cross says. “We desperately need ways to determine which patients will do better on which drugs to help with these clinical decisions.” Genetics may also provide clues. Laura Piccio, MD, Washington University neurologist at Barnes-Jewish Hospital, is working with the National MS Genetics Consortium to determine whether differences in patients’ DNA can help doctors identify the best treatments for those patients. “Many MS specialists think we now need to alter our goals for MS therapy and set our sights higher, aiming for freedom from disease activity altogether. That means no MS flare-ups, disability progression or disease activity seen on MRI scans,” Cross says. “We cannot do that for everyone with MS yet, but it’s becoming an increasingly feasible goal for the future.” n

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Becky Parks, MD, co-director of the John L. Trotter Multiple Sclerosis Center, is leading a study of daclizumab, an antibody that increases CD56+ natural killer T cells.

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Trigeminal neuralgia: matching treatment to patient A laser ablation probe uses focused heat therapy to destroy cancer cells from the inside out.

Stereotactic laser ablation offers surgery for Inoperable BRAIN TUMORS A probe-based, minimally invasive surgery using a laser system may change how neurosurgery will be performed in the future. The technique is having immediate impact on some patients with deep-seated or inoperable brain tumors. According to Eric Leuthardt, MD, a Washington University neurosurgeon at Barnes-Jewish Hospital and the Siteman Cancer Center, early results suggest the surgery has the ability to extend lives. “We are giving people with glioblastomas and high-grade tumors better outcomes with less morbidity” says Leuthardt of the ablation surgeries he performs with a system known as NeuroBlate, which is FDA-approved for neurosurgery. According to Leuthardt, Barnes-Jewish is the third hospital in the nation to have the laser system. The system delivers focused heat therapy to tumors while sparing surrounding healthy tissue. Surgeons achieve these results by using the system in coordination with intraoperative MRI scanning, real-time imaging and a fiber-optic probe with a unidirectional laser. Specifically, it delivers laser

interstitial thermal therapy. As the laser reaches a temperature between 48 and 52 degrees Celsius, it heats and destroys the cancer cells from the inside out. “The procedure is relatively well-tolerated, and our patients go home quickly,” says Leuthardt, who also is director of Washington University’s Center for Innovation in Neuroscience and Technology. Key indications for the procedure include inoperable brain tumors in the thalamus or insula, recurrent metastases after stereotactic radiation, recurrent glioblastomas and radiation necrosis that has led to swelling. But patients whose only other surgical option is biopsy may also be candidates for the procedure, Leuthardt says. While treatment is rendered in bursts lasting seconds to minutes, the full procedure takes five to six hours to complete due to the precise brain mapping needed to plot the path of the probe. Treatment is accomplished with the patient situated in an intraoperative MRI device. A single-use miniframe that is MRI-compatible is mounted to the patient’s head to help determine probe placement.

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The procedure requires a 2- to 3-millimeter incision and a burr hole about the size of a pencil’s diameter. A narrow probe with a fiber-optic laser is inserted through the burr hole into the center of the tumor. The unidirectional ability of the probe, coupled with real-time imaging, allows the surgeon to create heat fields that conform to the shape of the tumor and destroy it. “You can actually watch the heating and laser shots as they occur,” Leuthardt says. “Patients tend to go home a couple of days after surgery compared to being in the hospital for a week with the standard surgical approach. And the outcomes that we are seeing, at least very early on, are encouraging for aggressive tumors like glioblastomas,” Leuthardt says. “Without question we can provide a surgical option for people who may not otherwise have one.”

A patient with trigeminal neuralgia (TN) experiences excruciating pain characterized as recurrent extreme burning or electric shock, usually triggered by routine activities like eating, talking, brushing the teeth or touching the face. The most common cause of TN is an artery compressing the trigeminal nerve as it enters the brain stem. Because TN only affects four in 100,000 people annually, it is unfamiliar to many physicians and is often misdiagnosed. Joshua Dowling, MD, Washington University neurosurgeon at Barnes-Jewish Hospital, sees patients from all over the Midwest for treatment of TN. “Despite the rarity of the condition, I see 70 patients a year for surgery and many more for medical management. At Barnes-Jewish Hospital, we are fortunate to have the full range of treatments available, so it’s likely that one will be right for any given patient. Often physicians treating patients for TN may be reluctant to recommend surgery because they are concerned about the risks; however, there are low-risk options.”

Leuthardt is one of eight neurosurgeons in the nation using the laser ablation system. — M. KONROY

To view a video, visit bjhne.ws/ii.

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The most common cause of trigeminal neuralgia is an artery compressing the trigeminal nerve, shown in yellow above, as it enters the brain stem.

Dowling stresses that the goal of treatment is for the patient to be pain-free with a minimum of side effects. He starts with medical therapy, usually prescribing anticonvulsants such as carbamazepine or gabapentin. Only when drugs don’t manage the pain or the side effects are too onerous will he consider one of the following surgical procedures: • Microvascular decompression is a major intracranial procedure that does not generally result in facial numbness. “This procedure is effective 90 percent of the time, works immediately with a low complication rate and twothirds of the time is permanent. For a younger patient in good health, its longevity makes this a good choice,” says Dowling. • Percutaneous radiofrequency rhizotomy or glycerol rhizotomy doesn’t involve brain surgery and is safer for high-risk patients. Both provide immediate relief but can wear off. Multiple sclerosis patients can develop recurrent TN because of changes

in that disease, so percutaneous radiofrequency may be a better choice for them. • Stereotactic radiosurgery with a Gamma Knife focuses multiple beams of radiation on a precise area of the nerve root to deliver a high dose of radiation deep into the head. It injures the nerve enough to treat the pain while limiting numbness. For most patients, this treatment is ultimately effective, but it can take from two weeks to two months for the pain to subside. Some patients are afraid that numbing the trigeminal nerve will cause facial droop. Dowling says that droop is caused by injury to the facial nerve, not the trigeminal nerve. Dowling also notes that if the source of the pain is not from trigeminal neuralgia, surgery can potentially aggravate the condition. — M. Blackwood

To refer a patient, call 800-252-3627.

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Stroke patients benefit from carmaker’s efficiency

A process developed to increase efficiency and productivity in Japanese car factories has helped improve stroke treatment at Barnes-Jewish Hospital, report researchers at Washington University. By applying the principles of Toyota’s lean manufacturing process to identify inefficiencies, doctors reduced the average doorto-needle time for administration of the clot-busting drug tPA from 60 to 39 minutes. The findings were reported Oct. 18, 2012, in the journal Stroke. “We sought suggestions from everyone involved, from the paramedics who bring in patients to admitting clerks, radiology technologists, nurses and physicians,” says senior author Jin-Moo Lee, MD, PhD, Washington University neurologist at Barnes-Jewish Hospital and director of the Department of Neurology’s cerebrovascular disease section. “Once the inefficient steps were identified, we developed a completely new protocol that eliminated them. This new treatment protocol helped us achieve one of the fastest door-to-needle times in the country.”

In an average year, Washington University physicians treat 1,300 stroke patients at Barnes-Jewish. The hospital has a dedicated stroke team capable of quickly evaluating and treating patients with tPA. Ideally, the drug must be given within 60 minutes after a stroke begins, a period known as the “golden hour.”

The new treatment procedures, implemented in March 2011, lowered average door-to-needle times by nearly 40 percent and increased the number of procedures done within the golden hour from 52 to 78 percent. — M. PURDY

Door-to-Needle Time BARNES-JEWISH HOSPITAL

39 minutes

NATIONAL AVERAGE

96 minutes

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First Alzheimer’s prevention trials launched

Funded by a $4.2 million grant from the Alzheimer’s Association, the first Alzheimer’s prevention trials are currently enrolling participants. Randall Bateman, MD, a Washington University neurologist, is the principal investigator of the trials, which will determine if the disease can be halted or delayed before problems in memory and other brain functions become apparent. Bateman also serves as the director of the Dominantly Inherited Alzheimer’s Network (DIAN) Therapeutic Trials Unit at Washington University. The trials will be conducted through DIAN, an international research partnership focused on understanding inherited forms of Alzheimer’s. DIAN is headed by Washington University neurologist John Morris, MD. Bateman and Morris treat patients at Barnes-Jewish Hospital. Families enrolled in the study have inherited forms of Alzheimer’s that cause dementia at a much earlier age than the more common sporadic forms of the disease. Scientists have identified mutations in three genes that cause inherited Alzheimer’s.

Barnes-Jewish Hospital adopted lean manufacturing strategies to improve its delivery time of tPA to stroke patients.

Randall Bateman, MD, and doctoral student Justyna Dobrowolska look at specimens in the lab.

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An individual who inherits one of these mutations typically develops symptoms of the disease at approximately the same young age as his or her parent. DIAN researchers announced at the Alzheimer’s Association International Conference in 2011 that they could detect biological markers of presymptomatic disease in DIAN participants up to 20 years before the patients were expected to develop memory problems. With advice from a newly formed consortium of 10 pharmaceutical companies, DIAN researchers under Bateman’s leadership will select what they believe to be promising pharmaceuticals for the trials. They will give the drugs to family members who have an early-onset Alzheimer’s gene and biological markers of disease but do not yet have symptoms of dementia. The goal is to see if treatment can reduce the biological markers, potentially delaying or preventing the onset of symptoms.

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“Experimental treatments have risks, so to treat patients before symptoms occur, we must be sure that we have a firm grasp on who will develop Alzheimer’s dementia,” says Morris. “If we can find a way to delay or prevent dementia in DIAN participants, that would be a tremendous success story and very helpful in our efforts to treat the much more common sporadic forms of the illness.” In addition to Washington University, other institutions involved in DIAN are Harvard University, Massachusetts General Hospital, Brown University, Columbia University, Indiana University, the University of California Los Angeles, the University College of London’s Institute of Neurology at Queen’s Square and a consortium of the universities of Brisbane, Perth and Sydney in Australia. — M. PURDY

For more information or to register patients for potential participation in the trails, visit the DIAN registry at DIANXR.org.

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news Neurofibromatosis 1 and learning disorders

The Washington University and Barnes-Jewish Pituitary Center is experienced in treating prolactinproducing adenomas, which account for 30 percent of pituitary tumors.

Targeting pituitary tumors

The Washington University and Barnes-Jewish Comprehensive Pituitary Center is the St. Louis region’s first multidisciplinary center dedicated to treating patients with pituitary tumors. It offers equipment and techniques that include intraoperative MRI. Surgical approaches include transnasal endoscopic surgery and use of the Gamma Knife to target tumors with a concentrated beam of radiation. Julie Silverstein, MD, a Washington University endocrinologist at Barnes-Jewish Hospital, says management of pituitary tumors and related hormonal problems is best done by a collaborative team of specialists. This approach addresses surgical and nonsurgical issues and ensures patients receive coordinated care. “Typically, our patients are seen by an endocrinologist and neurosurgeon the same day and get streamlined referrals to related specialties, including ENT, radiation oncology or interventional neuroradiology,” says Silverstein. “Another of the center’s strengths is our experience treating prolactin-

producing adenomas, which account for 30 percent of pituitary tumors. Most can be treated medically, but others may require a combination of medication, surgery and radiotherapy.” The Pituitary Center also has expertise treating somatroph and corticotroph adenomas. Somatroph adenomas secrete growth hormone, resulting in acromegaly that causes enlargement of the jaw, hands and feet. Corticotroph adenomas produce ACTH and cause Cushing’s syndrome, characterized by weight gain, bruising skin and elevated blood pressure and blood sugar. The center’s multidisciplinary team provides long-term follow-up care for patients with pituitary tumors.

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Some patients require little or no treatment beyond periodic MRIs to monitor tumor growth. Others are followed after treatment to monitor for the development of hormonal deficiencies and regrowth. The center works closely with primary care physicians and endocrinologists who treat patients living outside the metropolitan St. Louis area and provides patient access to clinical trials. — M. Blackwood

For more information, or to refer a patient, call 800-252-3627.

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Neurofibromatosis 1 (NF1), is among the most common inherited pediatric brain cancer syndromes. Infants born with NF1 can develop low-grade brain tumors, but their most common problems are learning and attention difficulties. “While one of our top priorities is halting tumor growth, it’s also important to ensure that these children don’t have the added challenges of living with learning and behavioral problems,” says David Gutmann, MD, PhD, a Washington University neurologist at Barnes-Jewish Hospital and senior author of a recent study of inherited brain tumor disorder. “The results of our research suggest that learning problems in these patients can be caused by more than one factor. Successful treatment depends on identifying the biological reasons underlying the problems seen in individual patients with NF1.” According to Gutmann, who is director of the Washington University Neurofibromatosis Center, scientists are divided when considering the basis for NF1associated learning abnormalities and attention deficits. Mutations in the Nf1 gene can disrupt normal regulation of an important protein called RAS in the hippocampus. Initial work from other investigators had shown that increased RAS activity due to defective Nf1 gene function impairs memory and attention in some Nf1 mouse models.

However, earlier studies by Gutmann and collaborator David Wozniak, PhD, research professor in psychiatry, showed that a mutation in the Nf1 gene lowers levels of dopamine, a neurotransmitter involved in attention. In this Nf1 mouse model, Gutmann and his colleagues found that the branches of dopamineproducing nerve cells were unusually short, limiting their ability to make and distribute dopamine and leading to reduced attention in those mice. New research suggests that both sides may be right. In the latest study, Washington University postdoctoral fellow Kelly Diggs-Andrews, PhD, found that the branches of dopamineproducing nerve cells that normally extend into the hippocampus are shorter in Nf1 mice. As a result, dopamine levels are lower in that part of the brain. Charles Zorumski, MD, head of the Department of Psychiatry at Washington University School of Medicine, showed that low dopamine levels disrupt the ability of nerve cells in the hippocampus to modulate the way they communicate with each other. These communication

adjustments are a primary way the brain creates memories. Researchers then found that giving Nf1 mice L-DOPA, which increases dopamine levels, restored their nerve cell branch lengths to normal and corrected the hippocampal communication defect. L-DOPA also eliminated the memory and learning deficits in these mice. “These results and the earlier findings suggest that there are a variety of ways that NF1 may cause cognitive dysfunction in people,” Gutmann says. “Some may have problems caused only by increased RAS function, others may be having problems attributable to reduced dopamine, and a third group may be having difficulties caused by both RAS and dopamine abnormalities.” To customize patient therapy, Gutmann and his colleagues are now working to develop ways to quantify the contributions of dopamine and RAS to NF1-related learning disorders. — M. PURDY

To refer a patient, call 800-252-3627.

An inherited tumor disorder known as neurofibromatosis 1 shortens branches (far right) of the brain cells that make the important neurotransmitter dopamine. In a new study, researchers show that this decrease in dopamine impairs the hippocampus. Image courtesy of David Gutmann, MD, PhD

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Leadership

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Neurology and Neurosurgery

Neurosurgery

NFL funds study of the brain after concussions

Ralph Dacey Jr., MD, Chair, Department of Neurosurgery

Ralph Dacey Jr., MD, specializes in the treatment and science of cerebrovascular disease. He recently became president of the Society of Neurological Surgeons and is a member of the Fellowship of the Royal College of Surgeons. He is the former chairman of the American Board of Neurological Surgery, former chairman of the RRC and past president of the Congress of Neurological Surgeons and the American Academy of Neurological Surgeons. Dacey’s clinical interests include cerebrovascular disorders, aneurysms, AVMs, brain tumors, pituitary tumors and Gamma Knife procedures.

Since 2010, David Brody, MD, a Washington University neurologist at Barnes-Jewish Hospital, has headed one of seven national groups that provide clinical care to retired professional football players. A new project funded by NFL Charities, the charitable foundation of National Football League owners, will allow him to study the brain following repeat concussions. The research team will use magnetic resonance imaging (MRI) to measure damage in the brain’s white matter after repetitive concussive brain injury.

“There are a number of differences between blast-related injuries and repetitive sports-related concussions,” Brody says. “So it will be critical to validate the MRI method in a model of repetitive concussion to help us understand the meaning of any findings we may observe in human patients.”

Other institutions receiving NFL Charities grants include Columbia University, The Brigham and Women’s Hospital, Yale University and the University of Alabama at Birmingham. Studies at those centers will focus heavily on damage from concussions but also will look at the effects of helmet, face-mask and shoulder-pad designs on airway and cardiovascular care and a sleep apnea program that focuses on NFL players. — J. DRYDEN

In a study of repetitive sports-related concussions funded by the NFL, researchers will use MRI to measure damage in the brain’s white matter.

Michael Chicoine, MD Ian Dorward, MD Joshua Dowling, MD Robert Grubb Jr., MD Albert Kim, MD, PhD Eric Leuthardt, MD

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Julie Silverstein, MD

Vice Chair of Clinical Neurology Brad Racette, MD

General Neurology Sylvia Awadalla, MD, section chief

Neuroimmunology Anne Cross, MD, section chief

Neurorehabilitation Maurizio Corbetta, MD, division chief

Aging and Dementia John Morris, MD, section chief

Hope Center for Neurological Disorders Alison Goate, PhD, director

Neuroinfectious Diseases David Clifford, MD, section chief

Pediatric Neurology Michael Noetzel, MD, division chief

Neurological Critical Care Michael Diringer, MD

Sleep Medicine Kelvin Yamada, MD, section chief

The Charles F. and Joanne Knight Alzheimer’s Disease Research Center John Morris, MD, director

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ENDOCRINOLOGY

The Department of Neurology has 117 faculty members in 16 sections.

Epilepsy Edward Hogan, MD, section chief I n n o v a t e NE U R O L O G Y & NE U R O S U R G E R Y |

DeWitte Cross III, MD Colin Derdeyn, MD Christopher Moran, MD

David Holtzman, MD, specializes in research of the underlying mechanisms that lead to Alzheimer’s disease in an effort to improve its diagnosis and treatment. He was elected to the Institute of Medicine of the National Academy of Sciences in 2008 and serves as an editorial board member of Annals of Neurology, Molecular Neurodegeneration, Journal of Experimental Medicine and Science Translational Medicine. Holtzman was the recipient of the MetLife Award in 2007 and the 2003 Potamkin Prize from the American Academy of Neurology for research on Alzheimer’s disease.

Clinical Neurophysiology Mohammed Al-Lozi, MD, section chief

Wilson Zachary Ray, MD Keith Rich, MD Paul Santiago, MD Neill Wright, MD Gregory Zipfel, MD

David Holtzman, MD, Chair, Department of Neurology

Neurology

Last year, Brody’s group published a paper in the New England Journal of Medicine describing how they were able to use the same imaging method to analyze neurological function of United States military personnel who had suffered blast-related injuries in the wars in Iraq and Afghanistan.

INTERVENTIONAL Neuroradiology

Neurosurgery

Movement Disorders Joel Perlmutter, MD, section chief Neurofibromatosis Center David Gutmann, MD, PhD, director

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Neuromuscular Disease Alan Pestronk, MD, section chief Neuropsychology Steven Peterson, PhD, division chief

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Stroke Jin-Moo Lee, MD, PhD, section chief For a complete faculty list, visit neuro.wustl.edu.

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N ATIO N A L LE A DER S IN M E DI C INE

David Gutmann, MD, PhD

Colin Derdeyn, MD

Ralph Dacey Jr., MD

Randall Bateman, MD

AWARDS AND HONORS

Bateman named Knight Distinguished Professor of Neurology

Dacey named president of neurosurgery society

Derdeyn named Stroke Council chair-elect

Gutmann recognized for neurofibromatosis research

Randall Bateman, MD, has been named the Charles F. and Joanne Knight Distinguished Professor in Neurology at Washington University. He was officially installed in his new position at a ceremony in May 2012. He treats patients with dementia at the Memory Diagnostics Center at Barnes-Jewish Hospital and has been a faculty member at the university since 2006.

Ralph Dacey Jr., MD, neurosurgeon in chief at Barnes-Jewish Hospital and the head of the Department of Neurosurgery at Washington University School of Medicine, became president of the Society of Neurological Surgeons (SNS) in May 2012. His term will last one year.

Colin Derdeyn, MD, a clinician and researcher in stroke and cerebrovascular disease at the Mallinckrodt Institute of Radiology at Washington University and Barnes Jewish Hospital, was recently named the incoming vice chair and chair-elect of the American Heart Association (AHA) Stroke Council. He will assume his two-year term as chair on July 1, 2015.

David Gutmann, MD, PhD, a neurofibromatosis expert at Washington University, Barnes-Jewish Hospital and St. Louis Children’s Hospital, received the 2012 Friedrich von Recklinghausen Award. The Children’s Tumor Foundation gives the annual award to individuals who have made significant contributions to neurofibromatosis research and clinical care.

The Stroke Council, one of 16 scientific councils within the AHA/American Stroke Association, works to help identify, treat and prevent cerebrovascular disease and rehabilitate those who have it. Derdeyn also is a professor of radiology, of neurology and of neurological surgery at Washington University and the director of the Washington University and Barnes-Jewish Stroke and Cerebrovascular Center. He is an interventional neuroradiologist with an active practice involving the care of patients with brain aneurysms and stroke. His research focuses on ways to lessen the risk of stroke for patients with reduced blood flow to the brain and has included National Institutes of Health-funded clinical trials of angioplasty and stenting for narrowed brain blood vessels.

Gutmann also is the Donald O. Schnuck Family Professor in Neurology and director of the Washington University Neurofibromatosis Center. He has been caring for individuals with neurofibromatosis since 1994. Gutmann’s colleagues in the neurofibromatosis research community nominated him for the award, which is named for the German pathologist who first reported neurofibromatosis in 1882. About its 2012 recipient, the foundation notes, “Dr. Gutmann has a longstanding and pre-eminent role in neurofibromatosis 1 research and clinical care and a longtime involvement with the Children’s Tumor Foundation.”

Bateman developed a technique that made it possible to answer a critical question about Alzheimer’s disease: Do Alzheimer’s patients get brain plaques because they’re making more amyloid beta, the main ingredient of the plaques, or because their ability to clear amyloid beta from the brain is declining? Bateman’s innovation, known as stable isotope-labeling kinetics (SILK), made it possible to answer this question by tagging a component of the amyloid beta protein, thus allowing scientists to track amyloid beta production and clearance rates. His work shows that clearance appears to be impaired in patients with Alzheimer’s. Bateman also is associate director of the Dominantly Inherited Alzheimer’s Network (DIAN), an international collaborative study dedicated to describing the changes that lead to dominantly inherited forms of Alzheimer’s disease. Additionally, Bateman received the MetLife Foundation’s Promising Young Investigator Award in May 2012.

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Dacey, who also is the Henry G. and Edith R. Schwartz Professor of Neurological Surgery, joins a group of neurosurgical leaders that includes Harvey Cushing, MD, who is regarded as the father of modern neurosurgery and served as the first SNS president in 1920. Dacey’s predecessors as head of the hospital’s Department of Neurosurgery also served terms as president of the SNS. The society’s goals include promoting improvements in education and training for neurosurgical students and postgraduates, recognizing outstanding neurosurgical care, instruction and research, and encouraging the highest standards of care for patients with neurological diseases. Additionally, Dacey was awarded an honorary fellowship in the Royal College of Surgeons in Ireland (RCSI) at a ceremony held in Dublin in February. Dacey’s citation, read by RCSI council member Ken Mealy, notes, “Dr. Dacey is internationally recognized for his contributions to the understanding and treatment of conditions affecting the blood vessels in and around the brain.”

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Clinical Trials The following list represents open investigator-initiated and sponsored clinical trials available through the neuro-oncology program at the Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine.

Phase I/II Adaptive Randomized Trial of Bevacizumab Versus Bevacizumab Plus Vorinostat in Adults With Recurrent Glioblastoma David Tran, MD, PhD. WU-201207147

Phase II Study of Rindopepimut/GM-CSF in Patients With Relapsed EGFRvIII-Positive Glioblastoma (CDX110-06) David Tran, MD, PhD. WU-201209125

Exploration and Estimation of Intratumoral Concentration and Activity of Lapatinib In Vivo in Vestibular Schwannomas David Tran, MD, PhD. WU-201202092

Prospective, Multicenter Trial of NovoTTF-100A Together With Temozolomide Compared to Temozolomide Alone in Patients With Newly Diagnosed GBM David Tran, MD, PhD. WU-201206018

Phase III Trial on Concurrent and Adjuvant Temozolomide Chemotherapy in Non-1p/19q Deleted Anaplastic Glioma: The Catnon Intergroup Trial Clifford Robinson, MD. RTOG 0834 Phase I/Randomized Phase II Double-Blind Study of Either Dasatinib or Placebo Combined With Bevacizumab in Recurrent Glioblastoma David Tran, MD, PhD. CTSI N0872 Phase I/Randomized Phase II Trial of Either Dasatinib or Placebo Combined with Standard Chemoradiotherapy for Newly Diagnosed Glioblastoma Multiforme (GBM) David Tran, MD, PhD. CALGB N0877

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International, Randomized, Double-Blind, Controlled Study of Rindopepimut/GM-CSF With Adjuvant Temozolomide in Patients With Newly Diagnosed, Surgically Resected, EGFRvIII-Positive Glioblastoma David Tran, MD, PhD. WU-201202091 Phase II Study to Test the Safety and Efficacy of TVI-Brain-1 as a Treatment for Recurrent Grade IV Glioma David Tran, MD, PhD. WU-201202068

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Phase II Clinical Trial Evaluating DCVax-Brain, Autologous Dendritic Cells Pulsed With Tumor Lysate Antigen for the Treatment of Glioblastoma Multiforme (GBM) David Tran, MD, PhD. WU-201110176 qBOLD MR Measurements of Oxygen Extraction Fraction in Patients With Brain Tumors Tammie Benzinger, MD, PhD. WU-201107036 Classification of Optic Pathway Gliomas Using Advanced MRI Techniques Joshua Shimony, MD, PhD. WU-201105497 Multicenter Phase II Assessment of Tumor Hypoxia in Glioblastoma Using 18FFluoromisonidazole (FMISO) With PET and MRI Tammie Benzinger, MD, PhD. ACRIN 6684 Multisite, Randomized, Controlled Trial of Continuing Versus Discontinuing Statins in Patients With Brain Tumors Nina Wagner-Johnston, MD. WU-201209059

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Randomized, Double-Blind, Placebo-Controlled Trial of Lacosamide for Seizure Prophylaxis in Patients With High-Grade Gliomas David Tran, MD, PhD. WU-201205123 Natural History of Postoperative Cognitive Function, Quality of Life and Seizure Control in Patients With Supratentorial Low-Risk Grade II Glioma Clifford Robinson, MD. RTOG 0925 Analysis of Histological, Genomic, Molecular and Clinical Factors in CNS Cancer: The Neuro-Oncology Group David Tran, MD, PhD. WU-201111001 Prospective Evaluation of Advanced Neuromagnetic Resonance Imaging Techniques to Predict Long-Term Response to Therapy in Brain Tumors and Inflammatory Diseases That May Mimic Tumors Tammie Benzinger, MD, PhD. WU-201105273

To learn about other neuro-oncology clinical trials at the Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, visit trialsdirectory.wustl.edu. For additional information, or to refer a patient, send an email to siteman@ wudosis.wustl.edu or call 877-251-6485. To receive additional information about clinical trials and other research advances at Siteman, add your name to the email list at providersubscribe. wustl.edu.

Outcomes Analyses in Patients With Brain Tumors Michael Chicoine, MD. WU-201012772

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Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish Hospital and St. Louis Children’s Hospital. The School of Medicine is among the country’s leading medical research, teaching and patient care institutions, currently ranked sixth in the nation by U.S. News & World Report. As the university’s main adult teaching hospital for more than 90 years, Barnes-Jewish Hospital has been listed for 20 consecutive years on the U.S. News & World Report elite honor roll of “America’s Best Hospitals.” Washington University School of Medicine and Barnes-Jewish Hospital are nonprofit organizations and do not endorse commercial products or services.

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Physician editors: Ralph Dacey Jr., MD, chair, Department of Neurosurgery; Timothy Eberlein, MD, chair, Department of Surgery; Victoria Fraser, MD, chair, Department of Medicine; David Holtzman, MD, chair, Department of Neurology Contributing writers: Mary Jo Blackwood, Jim Dryden, Jim Goodwin, Mary Konroy, Michael Purdy

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