National Telehealth Conference Showcased UC Health’s Leadership Role
Pamela Kimmel, RN, BSN, Telestroke Program Manager for the UC Neuroscience Institute, speaks at last week’s National Telehealth Conference. Fifty-seven institutions from the United States and Canada attended a National Telehealth Conference, “Transforming Health Care Delivery and Academic Curriculum,” hosted by the University of Cincinnati College of Nursing on March 20-21. During the conference, members of the UC Neuroscience Institute showcased UC Health’s role as a telehealth leader through programs that include telestroke, telepsych and teletrauma. The event, with six specialized tracks each day, provided telehealth experiential learning for health care providers, administrators and educators. Attendees were given a first-hand look at various telehealth equipment in operation in health care and academic settings. The UC Neuroscience Institute, one of four institutes of the UC College of Medicine and UC Health, is using telemedicine in ways that have already benefited patients and is a leader in training partners in the use of telehealth and in providing telehealth services regionally. Telehealth opportunities are likely to continue to grow. In late February, Ohio Governor John Kasich signed into law a bill that will provide Medicaid coverage/reimbursement for telehealth/telemedicine. “Telehealth is the next major tool for health care reform and for meeting the Institute for Healthcare Improvement’s Triple Aim — improving patient experience via quality and satisfaction, improving health outcomes, and reducing cost,” says Anya Sanchez, MD, MBA, Director of Institute Planning and Administration at UC Health. “Providing telehealth/telemedicine services has great potential to reduce costs and provides patients with access to care that is not limited by geography.” UC Health has come to think about access in two different buckets, Dr. Sanchez says. “The first is internal, or how to connect ourselves better to ourselves within the health system. The second is external, or how to connect ourselves better to the community. Telemedicine plays a central role in both of those arenas.” Telemedicine serves as a new avenue to bring providers and patients together, spanning UC Health’s various facilities and numerous sites of care, Dr. Sanchez says. “We’re finding that leveraging telemedicine is enabling us to deliver care in a more coordinated and efficient manner, with fewer transitions, lower costs, and a better patient experience.” In one example, telemedicine has improved collaboration between emergency medicine physicians at UC Medical Center and psychiatrists at Psych Emergency Services (PES) on the Deaconess Health Campus. Telemedicine has enabled more rapid decision-making, which translates into shorter patient wait times, faster turnover of emergency department beds, a reduction in patient transport costs, and fewer staff resources required for registration. The Trauma team at UC Health’s Level I Trauma Center, led by Jay Johannigman, MD, is now able to provide the highest level of trauma expertise to West Chester Hospital, reducing the amount of time it takes to provide the right care to the right patient when time matters most. Another less dramatic but much more common example is our ability to connect the physicians at our medical office building to our patients at the Daniel Drake Center for Post-Acute Care. Instead of transporting our recovering patients to the medical office building (which can disrupt meals, medications, and physical therapy), some of our physicians now conduct “office visits” via telemedicine, saving time, cost, and discomfort to our patients. From an external standpoint, telemedicine also enables UC Health to deliver care across the region in a way never before possible. The UC Health Telestroke Network, an initiative that includes the Comprehensive Stroke Center at the UC Neuroscience Institute, enables physicians from the UC Stroke Team to “examine” stroke patients long-distance with the help of robots. UC Health launched the program in March 2012. Charles Doarn, PhD, research professor in the UC College of Medicine’s family and community medicine department, presented the keynote address, “State of Telehealth Across the U.S. and Beyond the Borders.” Dr. Doarn is special assistant in the Office of the Chief Health & Medical Officer at NASA Headquarters. He is also editor-in-chief of the Telemedicine & e-Health Journal, co-chair of the U.S. Government’s FedTel Working Group, and an international telehealth consultant. Conference partners included the UC College of Medicine, UC Medical Center, West Chester Hospital, Daniel Drake Center for Post-Acute Care, Cincinnati Department of Veterans Affairs Medical Center, Upper Midwest Telehealth Resource Center and Maple Knoll Communities. — Audrey Ronis-Tobin
A Patent for Treating Atypical Depression Awaits Fruition
Erik Nelson, MD, Associate Professor of Psychiatry and Behavioral Neuroscience, at the UC College of Medicine. Photo by Cindy Starr. When Erik Nelson, MD, got word in 2012 that he had been awarded his very first patent, he did not pop the champagne cork. The UC Mood Disorders Center psychiatrist, who was honored with other patent recipients at a recent UC men’s basketball game, admits it was a “cool feeling” to receive a patent. But any inclination to celebrate was tempered by reality. Like many ideas in science that lack sponsors, grants or the potential for large profits, the patent has been stuck in limbo, in a kind of patent purgatory. “It’s not uncommon for ideas not to go forward,” Dr. Nelson says. “Not because they wouldn’t potentially work, but because the funding isn’t there or the timing isn’t right.” Dr. Nelson’s patent is a “use patent” for histamine H3 receptor antagonists, including betahistine, as a treatment for atypical depression. Dr. Nelson has postulated that betahistine could help people with atypical depression by reversing one of the characteristics of their disorder – a dampened cortisol response to stress. But whether betahistine actually would convey such benefits is unknown, because no drug company has stepped forward to underwrite a clinical trial. Dr. Nelson, Associate Professor of Psychiatry and Behavioral Neuroscience, shares the patent with UC colleague Floyd “Randy” Sallee, MD, PhD. While Dr. Nelson views H3 receptor antagonists as a potential treatment for atypical depression, Dr. Sallee views them as a potential treatment for ADHD. Dr. Nelson arrived at his idea while he and two other colleagues were studying stress response in two subtypes of depression: melancholic and atypical. People with melancholic depression often have elevated levels of the stress hormone cortisol. They tend to sleep poorly and lose their appetite. People with atypical depression, in contrast, appear to feature a blunted hormonal stress response, with lower-than-normal cortisol levels. They tend to be sluggish and to eat and sleep too much. “Most anti-depressants have been shown to lower cortisol levels when they are excessively high in depression,” Dr. Nelson says. “It isn’t known whether they can reverse the blunting of the cortisol stress response that we saw in our study of patients with atypical depression.” That observation prompted Dr. Nelson to start looking at existing drugs, either FDA-approved or investigational, that had the effect of boosting the stress response. “We didn’t have evidence, but I started thinking, if these individuals have a blunted stress response, maybe something that raises the stress response would be helpful. It might give them more energy and reduce their appetite.” Dr. Nelson zeroed in on histamine, a neurotransmitter that helps regulate sleep, appetite, and alertness but had not been studied with regard to mood. The early anti-histamine drugs, as many allergy sufferers will remember, made you sleepy and lethargic and could also stimulate appetite. Those drugs worked by blocking a histamine receptor (H1). Dr. Nelson was looking at their opposite: histamine H3 receptor antagonists, which are thought to work by “removing the brakes on histamine” and allowing more of it to be released in the brain. In particular, Dr. Nelson was interested in betahistine, a drug that was already approved almost everywhere in the world as a treatment for vertigo. The drug has a special status in the United States. Although not FDA-approved, it is on a list of drugs that can be prescribed if the ingredients are shipped here in bulk and then compounded into a capsule at a pharmacy. Dr. Nelson submitted an investigational new drug (IND) application to the federal government, got approval to have the drug shipped from China, and ensured that the drug could be compounded at the UC College of Medicine. But as he worked to clear these hurdles, time marched on. His major research grant expired, and took on additional clinical duties to support his salary. When the patent was finally awarded, Dr. Nelson was no longer working on the project. Nevertheless, he had new hope that a drug company would license the patent idea. “It would be fun to resurrect this project,” he says, “to bring it back from purgatory.” – Cindy Starr
Research Finds Treating Depression Can Help People with Parkinson’s
Kim Seroogy, PhD, Director of the Gardner Center’s Selma Schottenstein Harris Lab for Research in Parkinson’s. Photo by Cindy Starr. Patients are routinely screened for stress and depression at the James J. and Joan A. Gardner Family Center for Parkinson’s Disease and Movement Disorders because of the Center’s own ground-breaking research, which provided the first tangible demonstration that life stress accelerates the progression of Parkinson’s disease. The research, performed in the Gardner Center’s Selma Schottenstein Harris Lab for Research in Parkinson’s, was led by Kim Seroogy, PhD, Lab Director and Professor of Neurology and Rehabilitation Medicine, and James Herman, PhD, Professor of Psychiatry and Behavioral Neuroscience. It was published online last September in the journal Molecular Psychiatry. “You might assume that it’s obvious that adverse life stress worsens Parkinson’s,” Dr. Seroogy says. “But it had never been explored experimentally. “It’s not just that the stress is causing someone to feel more emotional, uncomfortable or sad. Stress or depression superimposed on Parkinson’s actually impacts the disease process by worsening the health of brain cells. Parkinson’s involves the death of dopamine-producing cells inside the brain, and stress makes dopamine cells die faster and causes more of them to die. That’s the take-home message.” It is a message that is starting to resonate with physicians. “Until recently, many Parkinson’s doctors didn’t treat for depression when patients came in,” Dr. Seroogy says. “It wasn’t entirely their fault, because many symptoms of depression – such as slowness of movement and loss of facial expressions –– are masked by the symptoms of Parkinson’s. People chalked it up to a symptom of Parkinson’s, when actually it was a symptom of depression.” “Untreated depression may be making the Parkinson’s symptoms appear worse than they truly are,” says Alberto Espay, MD, a movement disorders specialist and Clinical Research Director at the Gardner Center. “Our profession is not doing as good a job as it could be in vigorously screening for and treating depression in Parkinson’s. At the same time, every line of evidence suggests that this is a ‘low hanging fruit’ in terms of providing an opportunity to improve overall function and enhance quality of life.” In editorial commentary published in CNS Neuroscience & Therapeutics, researchers from China acknowledged the Gardner Center research and concluded that “targeting stress-related disorders and preventing stress-enhanced PD [Parkinson’s disease] exacerbation will be important in clinical management of PD patients at all stages.” “Depression can be as disabling as the more commonly recognized motor symptoms of Parkinson’s disease,” adds Fredy J. Revilla, MD, Medical Director of the UC Gardner Center. “Research in this area is needed in order to improve the quality of life of our patients.” In addition to yielding valuable information, the research by Drs. Seroogy and Herman illustrates the value of small pilot projects. The research team began with a $14,000 pilot grant funded by the Sunflower Revolution Encore, a private fund-raiser hosted by Melody Sawyer Richardson in 2005. The team was further supported by a $50,000 grant from the Davis Phinney Foundation and $20,000 from the Parkinson’s Disease Support Network of Ohio, Kentucky and Indiana. Data acquired from these early rounds of small studies was ultimately used to secure a $1.7 million grant from the National Institutes of Health, enabling the team to conduct an in-depth study that produced meaningful results. Drs. Seroogy and Herman and their team members performed their research with rodents that 1) were given a lesion that modeled Parkinson’s disease and 2) were exposed to random stressors that resulted in their displaying the characteristics of stress-induced depression. The scientists discovered that the lesioned rodents that were exposed to stressors suffered significantly more loss of dopamine cells than the lesioned rodents that were not exposed to stressors. They also showed that chronic stress alone did not cause a loss of dopamine cells. Dr. Seroogy cautions that treating depression with anti-depressants will not cure Parkinson’s, which is a progressive disease. However, treatment with proper anti-depressant medication does have the potential to prevent acceleration of the course of Parkinson’s disease. — Cindy Starr
Graduate Students Seek Art Submissions for Brain Awareness Week
Sarah Cassella, a PhD candidate in the Neuroscience Graduate Program at UC, is coordinating local Brain Awareness Week activities. Photo by Cindy Starr. Brain Awareness Week in Cincinnati will have a new spin this year, thanks to doctoral candidates in the Neuroscience Graduate Program at the University of Cincinnati College of Medicine. In addition to providing hands-on educational demonstrations at the Cincinnati Museum Center, they will for the first time host a lecture in TED talk format and an art exhibit that features works “inspired by the brain.” They are seeking artwork from children, adults and professional artists. Brain Awareness Week, a national campaign held March 10-16, was started by the Dana Foundation to bring awareness to brain education and research. For several years volunteers from UC’s Neuroscience Graduate Program have joined in, sharing the biological wonder of the brain with elementary and middle school students. UC’s Brain Awareness Week activities will feature two events: • March 9-11: Demonstrations at the Cincinnati Museum Center, inside the Museum of Natural History and Science. Visit various stations in the LITE (Learning, Innovation, Technology and Education) Lab and finish by looking at a real human brain (free with the price of museum admission). • March 13, 5-8 p.m.: Art Show and Brain Talk at the Interact for Health ChoiceCare and Cincinnati Rooms at Rookwood Commons; Brain Talk begins at 6:30 p.m. (attendance and parking are free). The March 13 event features a talk about epilepsy by graduate students Rylon Hofacer, MS, and Isaiah Rolle, who work in the Danzer Lab at Cincinnati Children’s Hospital Medical Center. The lab, headed by Steve Danzer, PhD, explores the ways in which nerve cell development in the brain affects, and is affected by, epileptic seizures and autism. “Rylon and Isaiah are known to give fantastic talks while using good analogies to explain complex topics,” says UC’s Brain Awareness Week coordinator, Sarah Cassella, who works under Kim Seroogy, PhD, in the Selma Schottenstein Harris Lab for Research in Parkinson’s at the James J. and Joan A. Gardner Family Center for Parkinson’s Disease and Movement Disorders. “This week is going to be totally different from years past,” Ms. Cassella says. “We have more activities and have organized them better for participants.” The art exhibit will run simultaneously. Artistic contributions are being actively sought from the general public and are expected to include works by children, adults and professionals. “Anyone is welcome to submit artwork,” Ms. Cassella says. “Any medium is welcome, and any interpretation.” Ms. Cassella hopes the addition of an art show will broaden the event’s appeal. “It’s about brain awareness, not about being a scientist or knowing science,” she says. “There are a lot of people who dedicate their lives to brain research.” Although the events are aimed at children, materials will be available for adults on topics ranging from aging to disease prevention. Ms. Cassella’s interest in the brain was piqued by what she saw as vast differences in personality between her sister and herself. “I have a sister who is 17 months younger, and although people often confuse us for twins, she and I are day and night,” Ms. Cassella says. “I’m the scientist and athlete, and she is the artist and much more emotional. I was curious about why. It started off with psychology: why are we so different?” As a student at Oberlin College, Ms. Cassella had planned to study psychology. But she found herself riveted by brain biology and pursued a major in neuroscience. Now a fourth-year neuroscience graduate student, she expects to earn her doctorate in 2015. – Cindy Starr
10 Ways to Say, ‘I Love You, Brainy Valentine’
A physical will include a blood-pressure check. High blood pressure, or hypertension, in midlife is a risk factor for dementia. The day is here, and whether you have found the perfect card, have forgotten to buy flowers, or have been called in to work the night shift, you can still come through with a timeless gift of caring for your brainy Valentine. Here are 10 gift ideas from our experts on brain health at the UC Neuroscience Institute. Give them today or in the weeks and months to come. 1. Get your loved one to the doctor. If he has not had a physical recently, schedule one and offer to accompany him and take him to breakfast or lunch afterward. Even young people should have regular physicals as a general rule. No matter how old you are, your best defense against stroke is seeing a doctor who can help you modify any risk factors you might have with medication, a wellness program that stresses exercises and nutrition, or a smoking cessation program. Brett Kissela, MD, MS Professor and Albert Barnes Voorheis Chair Department of Neurology and Rehabilitation Medicine UC Comprehensive Stroke Center 2. Buy her blueberries. A preliminary study by UC researchers, based on a sample of nine older adults with early memory changes, found that daily consumption of blueberries helped improve memory. Blueberries contain polyphenolic compounds, most prominently anthocyanins, which have antioxidant and anti-inflammatory effects as well as other benefits for brain function. Robert Krikorian, PhD Associate Professor of Psychiatry and Behavioral Neuroscience UC Mood Disorders Center 3. Take your loved one for a power walk. Exercise is the best way to improve the brain and the heart. John M. Tew, Jr., MD Professor of Neurosurgery, Radiology and Surgery Neurosurgeon, UC Brain Tumor Center 4. Never let your loved one ride in your car without buckling his or her seat belt. Norberto Andaluz, MD Associate Professor of Neurosurgery Medical Director, UC Neurotrauma Center 5. Know the signs of stroke. Knowledge that a stroke is occurring or has occurred is critical, because medication must be administered within 4 ½ hours of the onset of symptoms. Because an individual who is having a stroke may be incapacitated or unaware that a stroke is occurring, assistance from a loved one or bystander may have lifesaving value. To simplify recognition of a stroke’s symptoms, the UC Stroke Team developed the mnemonic FAST: F: Facial numbness or weakness, especially on one side A: Arm numbness or weakness, especially on one side S: Slurred speech or difficulty speaking T: Time to call 911 Dawn Kleindorfer, MD Professor of Neurology and Rehabilitation Medicine Co-Medical Director, UC Comprehensive Stroke Center 6. If you’re taking in a movie or a show, do your loved one a favor by parking a little farther from where you need to be and using the stairs if you can. Thus far, exercise is the only proven disease-modifying (neuroprotective) intervention in Parkinson’s disease and cannot be made into a pill. A bit of exercise a day is love given to the brain. Alberto Espay, MD, MSc Associate Professor and Research Director Gardner Family Center for Parkinson’s Disease and Movement Disorders 7. Help your loved one’s brain stay “energy balanced,” by purchasing healthy, whole foods and by giving her a backrub so that she rests well. Atsuo Sasaki, PhD Assistant Professor and Cancer Researcher UC Brain Tumor Center and UC Cancer Institute 8. Encourage your loved one to seek help if you notice a radical change in mood or personality. And whether you see such a change or not, consider a gift of flavonoid-rich dark chocolate. Studies have shown that when eaten a few times a week in small amounts, it can improve arterial function, which can help lower blood pressure. What is good for the arteries is good for the heart and brain. Cal Adler, MD Associate Professor and Co-Medical Director UC Mood Disorders Center 9. Buy her a membership at the gym. Research shows that exercise can positively impact not only health and fitness, but also memory. The Brain Research Center at the University of British Columbia recently found that physical activity improves verbal and spatial memory in older adults with probable mild cognitive impairment. Matthew Flaherty, MD Associate Professor of Neurology and Rehabilitation Medicine UC Memory Disorders Center 10. Take care of yourself. As a surgeon, husband, and father, I think that you can show love to your family by taking care of yourself. Make a vow to take care of yourself spiritually, physically, and emotionally. Exercise, eat right, and watch your weight. By taking care of yourself, you are loving your family. Ravi Samy, MD Associate Professor of Otolaryngology Director, Adult Cochlear Implantation Program – Compiled by Cindy Starr
Brain Cancer Patients, Researcher Await Translation of Discovery into Clinical Trial
Xiaoyang Qi, PhD, in his laboratory at the Vontz Center for Molecular Studieson the UC Academic Health Center Campus. Photo by Cindy Starr for UCNI. Whenever Xiaoyang Qi, PhD, publishes a new paper or is interviewed by the media, the e-mails arrive in clusters from all over the world. Humble, hopeful and often desperate, they come from patients and family members eager to know when Dr. Qi’s discovery – a drug that has the potential to target multiple types of cancer – will be tested in a clinical trial for people. “My hope is sooner, not later,” Dr. Qi says. Dr. Xiaoyang Qi (pronounced ShawYung Chi) is a translational cancer researcher and Associate Professor in the Division of Hematology-Oncology, whose work straddles the UC Cancer Institute and the Brain Tumor Center at the UC Neuroscience Institute (both part of the UC College of Medicine and UC Health) as well as the Cincinnati Cancer Center, which includes the Cincinnati Children’s Cancer and Blood Diseases Institute. He is internationally recognized for designing nanovesicles known as SapC-DOPS, short for saposin-C dioleoylphosphatidylserine, while working at Cincinnati Children’s Hospital Medical Center in 2002. SapC-DOPS is a drug that has been shown in preclinical studies to cause several types of cancer cells – including brain cancer cells – to self-destruct, without causing harm to healthy cells or tissues. Still on the horizon is Phase I testing of the drug, which is manufactured as BXQ-350 by the Covington startup Bexion Pharmaceuticals. In 2013 Bexion received a rare $2.9 million Small Business Innovation Research Bridge Award from the National Cancer Institute, with Dr. Qi as co-Principal Investigator, to help it bring the drug into the clinical trial phase for patients with glioblastoma multiforme (GBM), the most common form of brain cancer. Moving beyond a single drug for a single target The drug represents a departure from most targeting drugs, which go after one gene or one protein. “These therapies, when they move to clinical trials, expose a lot of limitations,” Dr. Qi says. “To me, a single drug aimed at a single target seems an insufficient way to manage a tumor. First of all, you have a limited fraction of patients who might benefit. Secondly, cancer cells frequently resist the therapy by creating new mutations.” Even more problematic, Dr. Qi says, is the heterogeneity of tumors. “A single tumor in a single patient may consist of a variety of types of tumor cells, with different genetic background. So using a drug designed for only one type of mutation with a high level of expression may not affect cells with low-expression mutation within the same tumor mass. The unaffected cells can then revert to high-expression cells when the drug therapy is stopped.” SapC-DOPS itself is a combination of two compounds that occur naturally in all human cells: 1) SapC, a protein that is contained in the lysosomes; and 2) DOPS, a phospholipid, known as dioleoylphosphatidylserine, that is contained in cell membranes. The SapC-DOPS nanovesicle targets a lipid molecule called phosphatidylserine (PS) that has a ubiquitous presence on all cell membranes. In healthy cells, Dr. Qi explains, it is distributed asymmetrically, with greater abundance on the inside layer of the plasma membrane. But in viable cancer cells, its exposure is greatly increased on the outside of the cell membrane. This is true for cancers of the brain, pancreas, lung, breast, prostate and liver as well as for cancers that have metastasized from one part of the body to another. “I have about 100 cancer cell lines in my lab, and in all cases PS exposure is increased on the outer surface of the cell membrane,” Dr. Qi says. While working in his lab at Cincinnati Children’s, Dr. Qi discovered something fascinating about SapC. The fusogenic protein, he realized, could induce fusion between the outside PS microdomains of cancer cell membranes and the nanovesicles. This could lead, therefore, to a cancer-selective targeting by SapC-DOPS. Triggering a cancer cell’s demise Dr. Qi subsequently found that SapC-DOPS had the ability to trigger the cancer cell’s death through a series of biochemical reactions after the membrane fusion. When these nanovesicles were injected into animal models of cancer, the results have been dramatic: a shrinkage or elimination of cancers in the body and also the brain. Research published last year in the journal Molecular Therapy and PLOS ONE showed that animal models of brain and pancreatic cancer that were treated with SapC-DOPS “experienced clear survival benefits.” The research established PS as a biomarker for brain and pancreatic cancer and SapC-DOPS as a potential biotherapy for brain and pancreatic cancer. The promise of SapC-DOPS has riveted not only the American scientific community but also researchers and patients in China. Dr. Qi, who came to the United States from China in 1985, returns several times a year to work on parallel research with colleagues in Nanjing and Changzhou, Jiangsu province. “There is a desperate need for new cancer drugs in China,” Dr. Qi says. “Because the population of China is so large, the number of cancer patients in absolute numbers is very high.” In the e-mails Dr. Qi receives, desperate patients and families say they are willing to travel to the United States to participate in clinical trials. The better solution, he says, is for both countries to run the trials simultaneously. That day, he hopes, will not be too long in coming. About Xiaoyang Qi, PhD • Title: Associate Director and Associate Professor, Division of Hematology/Oncology, UC College of Medicine • Bachelor’s Degree: Nanjing University, 1982 • Doctoral Degree: Oklahoma State University, 1992 • Research Fellowship: Cincinnati Children’s Hospital Medical Center, 1996 • 2013 NIH funding: $305,799 • Nominee: 2014 Health Care Heroes, Innovator Category – Cindy Starr
Dr. Daniel Woo: Top 10 Researcher Advances Science of Stroke
Daniel Woo, MD, MS, at the UC College of Medicine. Photo by Cindy Starr for UCNI. The researcher who ranked No. 6 among all U.S. neurologists in funding from the National Institutes of Health in 2013 is right here at the University of Cincinnati Neuroscience Institute. Daniel Woo, MD, MS, was propelled to that position by outstanding mentors, a brilliant theory, and a determination to advance science in a way that would help thousands of people he would never meet. Dedicated to unraveling the genetic and environmental risk factors for intracerebral hemorrhage, a life-threatening type of bleeding stroke, Dr. Woo is principal investigator of three studies that were collectively funded at $5.65 million in 2013: the Genetics and Environmental Risk Factors of Hemorrhagic Stroke (GERFHS) study, the Ethnic/Racial Variations with Intracerebral Hemorrhage (ERICH) study, and the Stroke Genetics Network (SiGN) study. Dr. Woo, Professor of Neurology and Rehabilitation Medicine and a member of the UC Comprehensive Stroke Center at the UC College of Medicine and UC Health, earns another accolade today as he assumes the role of Vice Chair of Clinical Research in the Department of Neurology. The announcement was made by Brett Kissela, MD, MS, Professor and Albert Barnes Voorheis Chair. In his new role, Dr. Woo will work with Kim Seroogy, PhD, Vice Chair of Basic Research, to advance scholarly activity and research within the department. After graduating from the University of Virginia in 1990, Daniel Woo came to Cincinnati as a medical student, following a young woman he planned to marry. The relationship soon fizzled, but a lifelong passion for neurology began. Dr. Woo vividly remembers a scene during his first year, when he and a few other medical students watched the legendary Thomas Brott, MD, conduct a neurologic exam. “I remember that he had never seen this patient before,” Dr. Woo says. “We examined the patient, and because of the way the patient’s eyes were moving and how one side of the face was weaker, Tom predicted the lesion would be in a specific location and what it would look like. He even drew a little picture. I remember that I was a little skeptical. And then he showed us the CT scan, and he was exactly correct. It wasn’t a huge stroke; it was a smaller stroke in a smaller location in the brain, and he had identified it perfectly. And that was it: I was hooked on neurology. I was fascinated by that.” “I want to be like that guy someday.” Two years later, during his neurology rotation, Dr. Woo studied under Joseph Broderick, MD, then a rising neurologist and today the internationally known Director of the UC Neuroscience Institute. “Joe was a young academician, but he had this wonderful bedside manner, really bringing medicine to patients so that they understood what he was saying,” Dr. Woo says. “I remember thinking, ‘I want to be like that guy someday.’” After graduating, Dr. Woo did his residency at the Cleveland Clinic and then returned to UC for fellowship training in 1998. A native of Washington, D.C., he expected to stay in Cincinnati a year. But Drs. Brott and Broderick had recently pioneered the first effective treatment for acute ischemic stroke, a development that brought heightened prestige and energy to the program. Administered within a few hours of the stroke’s onset, tissue plasminogen activator (TPA) could break up clots that were blocking blood flow to the brain. Suddenly, people who previously would have died or become disabled by stroke were returning to their normal lives. Dr. Woo witnessed such a recovery when he treated Zoltan Balogh, a math professor at Miami University who had collapsed from a massive stroke while riding his bike. “We flew him down here, and there was a big clot in the right side of his brain,” Dr. Woo recalls. “We cleared the clot very quickly. Less than three months later he solved a math problem he had been working on since the 1960s. It was a great feeling to make an impact like that.” People Magazine’s story about Professor Balogh hangs framed in Dr. Woo’s office. Still, Dr. Woo sought something larger. “During my fellowship year I realized, ‘I’m a fine doctor and I take very good care of my patients.’ But what Joe and Tom did when they brought TPA into the world was to help thousands of people they had never met before. I remember thinking to myself, ‘I’d like to do something like that. I’d like to use my wits and brains to make that kind of contribution to help people. To advance science like that would be tremendous.’ ” A theory takes root By 2001 Dr. Woo had developed a theory, based on his observations, about high blood pressure (hypertension). “Whether your blood pressure is 180 over 100, or 120 over 80, your brain wants exactly the same amount of blood flow,” he says. Regulating the amount of blood flow can be a challenging task for the brain, which is unique in its vascular design. Elsewhere in the body, large blood vessels branch into ever smaller vessels, so that the pressure on the main vessel is widely distributed, Dr. Woo explains. But in the brain, which developed rapidly during evolution, very small vessels come off the main trunk “like alleys off an interstate.” These sensitive junctures are where hypertensive strokes tend to occur. Dr. Woo theorized that some people are well equipped to handle blood flow regulation, while others have a flaw in their DNA that makes them more at risk of mishaps, i.e., an intracerebral hemorrhage, or ICH. Only 60 percent of the risk for ICH can be attributed to high blood pressure and behavioral factors such as smoking and excessive alcohol consumption, Dr. Woo says. The other 40 percent remains unexplained. With this theory in mind, Dr. Woo secured a career development grant from NIH and earned a master’s degree in molecular genetics at UC. His next step was to acquire the grants needed
For Janis, Parkinson’s Clinical Trial Was a Life-Changer
Don and Janis Yelton are grateful for a clinical trial that has allowed them to enjoy their golden years. Photo by Cindy Starr. When Janis Yelton gratefully enrolled in a ground-breaking study at the University of Cincinnati Neuroscience Institute, one of four institutes of the UC College of Medicine and UC Health, she was wracked by pain from advanced Parkinson’s disease, taking 32 pills a day, and no longer able to work. Three years later, Janis still cries when she tells her story about the new treatment option that “saved my life.” Equally important, the results of the multi-site, Phase 3 clinical trial have been published. The study demonstrated the effectiveness of a constant infusion of Parkinson’s disease medications in gel form through a surgically implanted tube into the upper intestine, or duodenum. Alberto Espay, MD, a study author and Clinical Research Director at the James J. and Joan A. Gardner Family Center for Parkinson’s Disease and Movement Disorders, said that FDA approval of the treatment is anticipated soon. The clinical trial, funded by AbbVie (formerly part of Abbott), investigated a new delivery system of levodopa for patients with advanced Parkinson’s disease. When patients normally take levodopa orally, multiple times a day, it leads to the stimulation of dopamine receptors in the brain in a cyclic, rather than sustained, fashion. “The new system,” Dr. Espay said, “bathes the patient’s brain in dopamine at all times, which is what normally occurs in a healthy individual. This gives patients the continuity of stimulation of dopamine receptors and, therefore, more stability of function.” All study participants underwent a procedure to implant a duodenal tube and received either 1) medication-infused gel and placebo pills or 2) pills with real medication and a placebo gel. The gel formulation, calculated and mixed by investigators who were “blinded” to participants’ allocation, was pumped continuously during the waking hours. The study found that participants who received the medications in gel form experienced the greatest decrease in the number of hours with disabling symptoms (“off time”) of any available therapy for Parkinson’s disease. Levodopa gel correspondingly increased the number of high-quality hours (“on time”). In a reaffirmation of the “placebo effect” and the benefits of additional clinical oversight that study participants receive, those who received medication in pill form also showed significant improvement, although not to the magnitude of those who received the gel infusion. At the end of the three-month trial, patients who had received the gel placebo had the option of receiving the real medication through the implanted tube. Janis, now 67, was 51 and working in product development at Procter & Gamble when she first developed symptoms. While drinking coffee at her office, she noticed that her arm would move in a jerky, ratcheting manner as she set the cup down. “Then all of a sudden my pinkie finger started a little tremor,” she recalled. “I went to my family doctor and he suspected it was a brain tumor.” Janis was referred to a neurosurgeon, who examined her MRI and assured her that she did not have a brain tumor. Suspecting that she might have Parkinson’s disease, the surgeon referred her to a neurologist, who made the diagnosis. “I started to cry,” Janis recalled. “I said, ‘I don’t want it to be Parkinson’s’ — as if I had a choice. The neurologist said — and this was 16 years ago — if you’re ever going to have Parkinson’s, this is the time to have it, because we’re doing a lot of research.” Janis was able to tolerate her illness for the first few years. But at age 55 she was forced to leave her job because of fatigue and medication side-effects. Seven years after her diagnosis, she became overwhelmed by pain in her left arm and shoulder. “It was so bad that I asked my neurologist whether the arm could be amputated. And I meant it,” she said. “I used to lie on the living room floor and cry.” Although Parkinson’s disease is most frequently associated with tremor, involuntary movements (dyskinesias), stiffness and slowness, Dr. Espay said that pain is also a primary symptom, particularly among younger-onset patients. “It also can become common as a manifestation of non-motor fluctuations in patients with more advanced Parkinson’s disease.” Don Yelton, Janis’s husband and devoted caregiver, took early retirement when he was 60 in order to care for her. The disease is not hers alone, he said. “We have Parkinson’s, because what affects her affects me.” Finally, Janis and Don got a lucky break. Janis’s neurologist, Brian Maddux, MD, PhD, had heard about the new clinical trial and, although he was unaffiliated with UC Health, he referred her to Dr. Espay, who immediately recognized her as a candidate for the study. By this time Janis was taking medications every hour and a half. Because the study was randomized and double-blinded, Janis did not know whether the surgically implanted tube held the medications or a placebo. But after walking down the hospital hallway a few times after her surgery, she had more than an inkling. She turned to Dr. Espay and asked the unthinkable. “I said, ‘Dr. Espay, boy, do I feel good. I don’t have any pain. Do you think it’s gone? And he said, ‘I think it is.’ I cried. I said you don’t understand. I’ve had pain for 13 years. Then I saw another doctor crying and a nurse crying. Then it became a cry-a-thon.” Janis’s response to “the pump” was among the most dramatic in the study. She reduced her daily pill intake from 32 to 3 and was once again able to exercise, ride a bike, work in her garden and drive. Don was able to return to work part-time. “This isn’t a cure, and I still have some problems, but it’s the next best thing,” Janis said. “It’s an effective treatment option. We feel very blessed.” Although most patients wear the pump like a pager at the waist, Janis has cleverly hidden hers
Another Reason To Lose Weight? Obesity May Be Risky for Your Hearing and Brain
Ravi Samy, MD, at the UC Academic Health Center. Photo by Cindy Starr. Supporting evidence of a possible link between obesity and the spontaneous leakage of cerebrospinal fluid through the ear is presented by researchers at the University of Cincinnati Neuroscience Institute, one of four institutes of the UC College of Medicine and UC Health. The study, led by Ravi Samy, MD, Director of the Cochlear Implant Program at the UC Neurosensory Disorders Center, was published online last month in The Laryngoscope. Cerebrospinal fluid, or CSF, is a clear, colorless, constantly circulating fluid that bathes and cushions the brain and spinal cord. “Spontaneous cerebrospinal fluid leaks are on the rise,” says Dr. Samy, Associate Professor of Otolaryngology-Head and Neck Surgery at UC. “Traditionally, leaks were caused by infection, surgery or trauma, and were rarely spontaneous. Now spontaneous cases occur more often. Why that is happening, we don’t completely understand. But it is likely another reason why obesity is bad.” The rate of spontaneous CSF leak has increased from about 3 percent of all CSF leaks in the 1980s to between 25 and 59 percent of all leaks in recent years, according to studies published in 2009 and 2011. How does CSF escape from the brain and spinal cord to leak out of the ear? Sometimes a sac-like protrusion of the brain can swell through the openings in the skull. When that happens, CSF can leak out of the nose or ear as clear fluid or pool underneath the ear drum. Complications can include hearing loss or meningitis (an infection of the lining of the brain). The leak must be repaired surgically to stop further damage. When the authors looked back at the medical records, they found 55 patients who had surgery to repair a CSF leak from the ear. They asked, “Why had these leaks sprung and did they affect hearing?” Surprisingly, the leaks were spontaneous in three-quarters of these patients. After surgery, 10 percent of patients had hearing loss. The patients had one striking feature in common: they were obese, with a body mass index (BMI) of 30 or more. “This study is evidence of yet another health risk of obesity,” Dr. Samy says. “Obese patients face a higher risk of complications not only during surgery to repair the leak, but also for another leak erupting after repair as well as for meningitis and hearing loss.” Hearing loss is compounded by the strain of obesity itself, the CSF leak and potential risks of the surgery. Controversy continues about how CSF leaks might develop. Experts agree that sac-like protrusions can be the result of a birth defect or chronic ear infection or trauma. Obesity may also play a role because it often occurs with intracranial hypertension. The increased pressures may cause a wear-and-tear affect, thinning the inside of the skull that then creates an opening for the CSF to flow out into the ear. Dr. Samy reaffirms the importance of maintaining a healthy weight. CSF leaks can be repaired, but the surgery can be complicated and leakage can recur. Given the spike in the rate of spontaneous CSF leaks, he adds, doctors should be alert for symptoms in their overweight patients. Co-investigators of the study were Hwa J. Son, MD; Alexandre Karkas, MD, MSc; Patrick Buchanan, DO; Jonathan P. Giurintano, BA, BS; Philip Theodosopoulos, MD; and Myles L. Pensak, MD. – Mary Kemper
A Surprise DAISY Award for ‘Mama Berra,’ the Singing Nurse
Judy Berra, RN, and thankful patient Mark Barr, the UC Bearcat who was severely injured in a September car crash. Photo by Cindy Starr. She was his nurse, but he called her “Mom.” She meant that much to him. Day after day she monitored his slow recovery in the UC Neuroscience Institute’s intensive care unit (NSICU), checking his signs, watching for changes, singing songs in her sweet soprano voice to move the healing along. When she left the room, he later remembered, he sometimes cried, begging her to come back. She complied. And when a shift opened up on her day off, she grabbed it, knowing that her presence made a difference for her young patient. That special kind of above-and-beyond earned Judy Berra, RN, a DAISY Award on Wednesday at the UC Medical Center. Attending the ceremony, a surprise for Ms. Berra, was her memorable patient: Mark Barr, a freshman wide receiver on the UC football team who had suffered a life-threatening traumatic brain injury in a Sept. 21 car accident. The accident also injured a second UC football player and claimed the life of UC freshman offensive lineman Ben Flick. Mark’s parents, Tia and Mark Barr of Ft. Lauderdale, Fla., submitted one of three nominations for Ms. Berra, describing her as “a godsend” whose support was unwavering. “She comforted us and kept our spirits up,” they wrote. “Her voice is unforgettable. We believe in our hearts that she was sent by God to protect our son.” “The family refers to Judy as Mark’s guardian angel,” wrote Amy Porta, RN, BSN, Clinical Manager of the NSICU, who also nominated Ms. Berra. “Judy ensured that she cared for him every day she was on shift, but in addition she picked up extra shifts to alleviate the family’s fears.” The DAISY Award is sponsored by the DAISY Foundation, an international program that recognizes “extraordinary nurses who make an enormous difference in the lives of so many people.” DAISY, which stands for “diseases attacking the immune system,” was founded by a family that lost a son to an autoimmune disease. Ms. Berra, sometimes referred to as “Mama Berra” or “the Singing Nurse,” says the secret to great nursing is “compassion for feeling what other people are feeling and trying to ease that pain. It’s not just about physical caring for the patient. A lot of it is mental. I fell in love with Mark’s parents, which made me want to make sure he made the best recovery possible.” Mark Barr was hospitalized in the NSICU for 30 days. Ms. Berra didn’t really get to know Mark until the end of his stay, when he started waking up from his coma. “He became reliant on me because he knew me best,” Ms. Berra says. “That’s when I grew to love a super great young man, not just his parents. He was sweet and humble and childlike. That’s when he started calling out for me. He was just in a place where he didn’t want to be alone. After enduring all of that, I wouldn’t want to be alone either.” On Wednesday, Mark was proof of the kind of outcomes a tertiary neurocritical care unit can produce. Though not 100 percent recovered, Mark says he is “pretty close.” This week also marked his return to classes at UC, where he is majoring in sports administration and minoring in digital design. An artist who writes poetry, he says he can draw “anything I can see.” – Cindy Starr