From the Lab to the Bedside, UC Brain Tumor Center Makes Strides in Effort to Tame Glioblastoma
From left: Xiaoyang Qi, PhD, Rekha Chaudhary, MD, and El Mustapha Bahassi, PhD. Families who confront glioblastoma multiforme, an aggressive brain cancer, shoulder a particularly harsh burden of disease. The cancer, as the word “multiforme” suggests, comes in many forms. Its heterogeneous nature and diffuse form make it difficult to treat. But patients and families can take some solace in knowing that research scientists and clinicians around the world are making progress in their effort to find what Dr. Ronald Warnick, Medical Director of the UC Brain Tumor Center, calls “the holy grail” – the cure for glioblastoma multiforme. From the laboratory bench to the patient’s bedside, medical scientists are exploring every molecular nook and cranny of the difficult cancer while prodding and poking it with experimental therapies and technologies. Much of that work is taking place right here at the UC Brain Tumor Center, which is part of the UC Neuroscience Institute and the UC Cancer Institute. Here, more than a dozen medical scientists are conducting laboratory, translational and clinical research. For patients in the Greater Cincinnati community who have been diagnosed with glioblastoma, the ramifications are profound: They have access to clinical trials that are beginning to produce hopeful results. Rindopepimut in the news A handful of patients at the UC Brain Tumor Center participated in a Phase 2 study of rindopepimut, a drug that stimulates the body to use its own immune system in the fight against glioblastoma. This group of patients had experienced a recurrence of their glioblastoma and also had a specific type of genetic mutation, referred to as EGFRvIII. This mutation, or “oncogene,” is found in about 30 percent of patients with glioblastoma. Last month, in an interim analysis of the Phase 2 trial (known as ReACT), researchers reported that 125 study participants who took rindopepimut along with bevacizumab (Avastin) had improved survival compared to those who were treated with other drugs and chemotherapy. The data was presented by David Reardon, MD, of the Dana-Farber Cancer Center and Harvard Medical School, at a platform presentation at the Society for Neuro-Oncology’s annual scientific meeting in Miami. “There has been very little data from all the clinical research in the recurrent glioblastoma setting that has shown promise,” says Rekha Chaudhary, MD, a neuro-oncologist at the UC Brain Tumor Center and Principal Investigator of the Cincinnati portion of the trial. “This data gives the whole brain tumor community –patients, caregivers, scientists and medical professionals — the one word we are all searching for: hope.” Rindopepimut is an investigational drug developed by Celldex Therapeutics; Avastin is an FDA-approved drug marketed by Roche. The study results showed that rindopepimut was most effective in patients who had not previously taken Avastin. A separate Phase 3 trial (ACT IV) in patients newly diagnosed with glioblastoma is ongoing at multiple centers around the world, including the UC Brain Tumor Center. In this study, patients with the EGFRvIII mutation are treated with rindopepimut along with temozolomide, a commonly used chemotherapy drug. An additional half-dozen clinical trials exploring treatments for glioblastoma are also underway at the UC Brain Tumor Center. Positive results for tumor treating tields (TTF) therapy In other news of interest, investigators at the recent Society for Neuro-Oncology meeting in Miami released the initial results from a large randomized Phase 3 trial, which used the Novo TTF-100A tumor treating fields therapy in addition to temozolomide in patients newly diagnosed with glioblastoma. Tumor treating fields therapy involves the delivery of a low-intensity electric field with electrodes placed directly on the skin in the region surrounding the tumor. The electric field disrupts cell division and leads to subsequent cell death (apoptosis). The researchers found that the 2-year survival in this study of 200 participants was 1.5 times greater for those who received the Novo-TTF device than for those who received temozolomide alone. The study results were so promising that the study was discontinued midway through, and the tumor treating fields therapy was offered to study participants who were receiving temozolomide alone. “Just within the last month we have two new positive trials for patients with brain cancer,” says Richard Curry, MD, a neuro-oncologist at the UC Brain Tumor Center. “We are actively chipping away at these aggressive tumors and continue to move closer to the day when a cure becomes reality.” In the laboratory In laboratories on the UC Academic Health Center campus, seven research scientists are searching for glioblastoma’s molecular Achilles’ heel. Working collaboratively yet independently, and with the support of grants from local foundations, the federal government, and Walk Ahead for a Brain Tumor Cure, they are striving to find a way to halt the tumor’s growth and its ability to elude conventional therapies. Bahassi and Stambrook Laboratories El Mustapha Bahassi, PhD, Research Assistant Professor of Medicine, and Peter Stambrook, PhD, Professor of Molecular Genetics, Biochemistry and Microbiology, are studying biomarkers that may soon help guide doctors’ treatment of glioblastoma multiforme. Using simple blood tests, Dr. Bahassi and his team are studying DNA that breaks off from the tumor and flows through the bloodstream to identify genetic abnormalities in individual tumors. Learn more » Desai Laboratory Pankaj Desai, PhD, Professor of Pharmacokinetics and Drug Metabolism at the Winkle College of Pharmacy, and his team are exploring the potential of letrozole, a drug administered orally to treat breast cancer, to treat brain cancer. Learn more » Driscoll Laboratory James Driscoll, MD, PhD, Assistant Professor of Hematology-Oncology, and his team have tested hundreds of different small-molecule compounds for signs of effectiveness in the treatment of glioblastoma multiforme. They have developed a high-throughput, automated screen to rapidly test hundreds of compounds at the same time. Learn more » Plas Laboratory David Plas, PhD, Associate Professor of Cancer Biology, is focused on a protein known as S6Kinase1, or S6K1. The protein is in a pathway downstream of another protein, PTEN, a major tumor suppressor that is frequently mutated in brain cancer. The deficiency of PTEN occurs in all four molecular subtypes of glioblastoma. Dr. Plas
Symposium Explores Strategies for Managing Medication-Resistant Epilepsy
David Ficker, MD, Director of the Epilepsy Monitoring Unit at the UC Epilepsy Center. Strategies for managing epilepsy is the focus of a free symposium for patients, families and caregivers on Saturday, Nov. 22, at the Daniel Drake Center for Post-Acute Care. One of those strategies involves encouraging patients whose seizures are not controlled by medication to undergo 24-hour monitoring, says David Ficker, MD, Director of the Epilepsy Monitoring Unit (EMU) at the UC Epilepsy Center. When Dr. Ficker and his team see patients who have failed to get relief from seizures after trying two medications, they recommend a stay in the EMU so that they can determine what type of seizures they are having and where the seizures are coming from. “Testing in the EMU will tell us what direction we can take to get the seizures under control,” Dr. Ficker says. People who have failed to get relief after trying two medications are said to have medication-resistant or “refractory” epilepsy. Unfortunately, the success rate for a third medication after two have failed is only 5 percent, Dr. Ficker says. “The success rate for a fourth, fifth or sixth medication is even lower.” Nevertheless, patients will often spend 15 to 20 years coping with refractory epilepsy before undergoing testing in an EMU. Testing in the EMU can determine whether a patient is a candidate for surgery or brain stimulation, Dr. Ficker says. Patients with temporal lobe epilepsy can often be successfully treated with surgery, which involves removing a small piece of the brain where the seizures are originating. “If I see someone who has failed two drugs and is diagnosed with temporal lobe epilepsy, we’ll probably recommend to that patient that they consider surgery.” Dr. Ficker may recommend other treatments, including vagus nerve stimulation (VNS), for patients whose seizures are not emanating from the temporal lobe. “We try to get aggressive in seizure treatments for patients with refractory epilepsy,” Dr. Ficker says. “This could involve a medication change or looking at other options such as stimulation devices or a carbohydrate-restricted diet.” The UC Epilepsy Center has been approved to implant a device known as the RNS responsive stimulator, a programmable, battery-powered device that delivers electrical pulses to the brain via implanted leads. The device also includes EEG recording capabilities. When the device detects abnormal brain activity (an impending seizure), it responds by producing a mild stimulation that “re-sets” brain activity to its normal level, thereby stopping the seizure in its tracks. The device is manufactured by NeuroPace. Helping patients with medication-resistant seizures is important because of a small but real risk known as SUDEP, or sudden unexpected death in epilepsy. SUDEP is the sudden death of a person known to have epilepsy when no other reason for the death exists. It is seizure-related and is likely the result of respiratory or cardiac arrest. Studies in the medical literature indicate that SUDEP occurs in one of every thousand people with epilepsy, Dr. Ficker says. “Overall, it may not seem like a huge number. But if you look at specific populations of people with epilepsy, the rate is higher in patients who are classified as having poorly controlled seizures. We think that poorly controlled seizures is a risk factor for SUDEP.” Historically, many physicians have avoided discussing SUDEP with their patients who have epilepsy because the risk is low and they fear of causing unnecessary anxiety. “People with epilepsy are likely to have a lower risk of SUDEP than the risk that they will suffer an injury from a seizure or seizure-related driving accident,” Dr. Ficker says. But new research, published in the journal Epilepsia, suggests that although most patients and caregivers “reported feelings of fear, anxiety, and sadness after first hearing of SUDEP,” they nevertheless wanted to discuss it with their doctor. Further, while researchers reported that this worry “escalated with knowledge of SUDEP and increased epilepsy severity,” approximately one-half of patients and caregivers “believed that knowledge about SUDEP would influence their epilepsy management.” Patients, families and caregivers who attend the Nov. 22 epilepsy symposium will learn about all currently available means of controlling seizures. – Cindy Starr, MSJ
UC Neuroscience Institute Marks 15th Anniversary with Landmark $14M Gift
From left, members of the extended Gardner Family: Peggy Gardner Johns, Gary Johns, Lori Gardner Sommer, Laura Mueller, Adam Mueller, Keri Young and Eric Mueller. Photos by Jay Yocis / University of Cincinnati. The University of Cincinnati Neuroscience Institute celebrated its 15th anniversary last Saturday with a gift for the ages: a transformational, $14 million commitment from the James J. and Joan A. Gardner Family Foundation. Peggy Gardner Johns, the daughter of James and Joan Gardner, announced the gift before an audience of donors, physicians and researchers at the Queen City Club. “As a result of long-standing friendships and the superb medical care our mother has received, we are honored and privileged to announce that we are making a significant impact on the future of the UC Neuroscience Institute,” Mrs. Johns said. “We are providing a commitment of $14 million to help provide the Institute with a new home. We envision this home not merely as a facility. Rather, we envision a vibrant space that is alive with comprehensive care, multi-disciplinary clinics, and the kind of animated brain-storming that leads to revolutionary new treatments.” Mrs. Johns’s remarks were met with gasps, tears and a standing ovation. Official news release >> News report on BizJournals.com >> Joseph Broderick, MD, Director of the UC Neuroscience Institute, shared the history of the Institute’s relationship with the Gardner family, which began when Joan Gardner came under the care of Alberto Espay, MD, a specialist at what was then known as the Parkinson’s Disease and Movement Disorders Center. “Alberto’s care made a major difference for her,” Dr. Broderick recalled. “Joan’s husband and the rest of the family became more interested in how they could accelerate research and better treatment for patients with Parkinson’s disease. This led to several gifts: a $500,000 gift for a nurse navigator and a $5 million gift over five years to establish in 2008 the James J. and Joan A. Gardner Family Center for Parkinson’s Disease and Movement Disorders.” Peggy Gardner Johns announced a landmark gift from the Gardner Family Foundation. Mrs. Johns said she would never forget the day her father announced: “I want to eradicate this disease.” When the family’s five-year commitment came to a close, Mrs. Johns said, they found themselves at a crossroads. “After a 10-year partnership with the UC Neuroscience Institute – and with the Parkinson’s center in particular — would we go forward in the area of Parkinson’s? Would we switch paths? Or would we veer onto a new, wider, multi-lane highway that led to broad-based neuroscience eminence in Cincinnati?” Joseph Broderick, MD After months of meetings, brainstorming sessions and visits to other nationally recognized centers, the family approached a decision. Instrumental in the process was the Gardner Family Foundation Sub-Committee, which comprises Tom Mueller, Adam Mueller, Eric Mueller, Gary Johns and Kyle Johns. Together they did “the heavy lifting for the family by attending many extra meetings and bringing back recommendations so that the family could make an informed decision,” Dr. Broderick said. The family’s decision resulted in the largest gift ever made to the UC Neuroscience Institute. “Today – tonight – we come another giant step closer to a new, higher benchmark of excellence – a transformation of the entire Neuroscience Institute and its 11 centers into a hallmark of integrated patient care, research and community partnership,” Dr. Broderick said. Other 15th Anniversary Highlights UC President Santa J. Ono, PhD, who provided opening remarks, praised the Institute for its growth and success over the last 15 years under the leadership of Dr. Broderick and co-founder John M. Tew, Jr., MD. “The UC Neuroscience Institute was first envisioned by a young neurosurgeon more than 30 years ago, and since its founding 15 years ago, in 1998, we have succeeded,” President Ono said. “We have become very, very good at acting as one in the treatment and research of neurological disease. We have become so good that the UC Neuroscience ranks among my very top priorities as President of the University of Cincinnati. As an aside, let me say that while we have the #HottestCollegeinAmerica, we also have the #HottestNeuroscienceInstitute.” UC President Santa J. Ono, PhD, commended UC Health, the UC College of Medicine and the UC Neuroscience Institute for working together “as one.” President Ono described the Institute as a physical and virtual entity that is found in many different buildings, laboratories, operating rooms, and conversations. “It embraces different people, different specialties, and different neurological diseases and conditions,” he said. “It touches nearly everyone in our community in some way, and it reaches out to all corners of the world through discovery and education. “The UC Neuroscience Institute was created to break down the silos that separated individual specialties and bring them together to generate optimal treatment and new discoveries for the benefit of our patients,” Dr. Ono said. “It was meant to spark ideas, to cross-pollinate, to unleash discoveries. It was meant to promote healing and to find cures. It was meant to be local and global at the same time.” From left: Peggy Gardner Johns, Lori Gardner Sommer and Sandy & Bob Heimann. Thomas Boat, MD, who the day before had completed his duties as Dean of the UC College of Medicine and Vice President for Health Affairs, shared highlights from the Institute’s last five years. Those highlights included impactful donations from members of the community: • Gifts of more than $2 million from Sandy & Bob Heimann established the Sandy & Bob Heimann Chair in Research of Alzheimer’s Disease at our Memory Disorders Center • A $2 million gift from the Harold C. Schott Foundation helped launch the Brain Tumor Molecular Therapeutics Program, the first U.S. research program dedicated to studying brain metastasis. • A $2 million gift from George Wile created a neuroscience research endowment, which helped launch the Neurobiology Research Center • The Charles Shor Foundation helped fund the SMILE Study — the first blinded, randomized, controlled trial of stress reduction in epilepsy, which will result in the
More Muscle for UC Neuromuscular Center
Dr. John Quinlan, seated, Medical Director of the UC Neuromuscular Center, with members of the “Myoblasts” at the 2014 MDA Muscle Walk. Photo by Cindy Starr. Sometimes good things really do come to those who wait. That could be the message of the year for people with neuromuscular disorders — terrible, uncommon diseases that steal patients’ muscle strength and often their lives. This is the year that the Ice Bucket Challenge became an Internet sensation, bringing an unprecedented flood of exposure and research funds to the “orphan” disease ALS, one of the most sinister neuromuscular disorders. And this is the week that the University of Cincinnati Neuroscience Institute’s Neuromuscular Program became a little more muscular. It joins nine other neuroscience specialties as an official Center of Excellence. This is welcome news for patients and families affected by the spectrum of adult neuromuscular disorders, which include: Acquired neuropathies (diabetes related to toxins and chemotherapy, etc.) ALS (amyotrophic lateral sclerosis or Lou Gehrig’s disease) Cervical and lumbar radiculopathies Charcot Marie Tooth disease Guillain-Barre Inflammatory myopathies (dermatomyositis, polymyositis, inclusion body myositis) Metabolic myopathies (mitochondrial disorders, myophosphorylase deficiency) Muscular dystrophy Myasthenia gravis and neuromuscular junction disorders Spinal muscular atrophy “Becoming a center of excellence gives assurance to our patients that we provide cutting-edge neuromuscular care,” says John Quinlan, MD, Medical Director of the Neuromuscular Center. “It will help in the long term to raise awareness for these poorly understood diseases and to help us develop future benchmarks in three core areas: research, treatment and education.” Center status also brings new visibility within the region, says Hani Kushlaf, MD, right, Director of the Neuromuscular Medicine Fellowship Program. “We are known for our expertise in delivering tertiary and quaternary neuromuscular care. Our elevated status will help us going forward to achieve additional milestones.” The Center’s clinical team is led by five board-certified neuromuscular specialists. Patients with the most complicated neuromuscular disorders are seen in two MDA Clinics (one at the UC Medical Center and the other at University Pointe in West Chester, Ohio). Robert Neel, MD, heads up the recently established UC Health ALS Clinic at the Daniel Drake Center for Post-Acute Care. “Our team provides a full range of neurophysiological testing for neuromuscular diseases — from the most common carpal tunnel syndrome to the rarest botulism poisoning,” Dr. Quinlan says. “We offer neuromuscular junction testing, and Dr. Kushlaf performs single-fiber EMG for diagnosis of the most difficult neuromuscular junction diseases. In the educational arena, the neuromuscular team has a long track record of excellence. Dr. Quinlan is a legendary professor at the UC College of Medicine, and his collection of silver apples awarded by his students is sparkling proof. Dr. Neel directs an annual ALS workshop and, looking forward, a dedicated neuromuscular fellowship training program will begin in July 2015 under the direction of Dr. Kushlaf. Perhaps of greatest importance to desperate patients who often find that little can be done to stop or delay muscle wasting or deterioration, the Center is now primed to play a larger role in laboratory and clinical research. Earlier this year, Laura Sams, MD, began a treatment trial of rituximab for the treatment of myasthenia gravis. A collaboration is under way with Cincinnati Children’s Hospital Medical Center in an effort to correct the primary molecular defect in myotonic dystrophy type I, and Dr. Kushlaf is pursuing additional basic science studies of myasthenia gravis. As the Neuromuscular Center gains momentum, it also stands to benefit from added community engagement. The neuromuscular team has played a leadership role in the annual MDA Muscle Walk and the Walk to Defeat ALS, and Dr. Neel was not to be left out of the Ice Bucket Challenge. He did his own challenge at the College of Medicine and then got drenched a second time when helping to pour ice on UCMC CEO Lee Ann Liska and his boss, Brett Kissela, MD, the Albert Barnes Voorheis Chair of the Department of Neurology and Rehabilitation Medicine. A partially soaked Dr. Rob Neel, left, with Lee Ann Liska and Dr. Brett Kissela. – Cindy Starr
From Stroke to Dystonia to Migraines, Botulinum Toxin Injections Bring Comfort
At the University of Cincinnati Neuroscience Institute, the beauty of widely used wrinkle-vanishing injections is more than skin deep. Specialists are injecting drugs best known for their cosmetic uses to help patients live better and more comfortably with conditions as wide-ranging as stroke, cervical dystonia, multiple sclerosis, cerebral palsy and chronic migraine. In the hands of neuroscience specialists, the injections can ease disruptive and even painful spasms in the legs, arms, hands, feet and neck. The family of drugs come from a protein derived from the neurotoxin-producing bacterium Clostridium botulinum (pronounced botch-oo-LINE-um), an organism that can cause life-threatening botulism. The four available brands are Botox (marketed by Allergan), Dysport (Ipsen Biopharm), Xeomin (Merz Pharma) and Myobloc (USWorldMeds). “Lots of people have heard about botulism and that it can be very bad for you as a disease process, because it can paralyze your whole body and cause you to eventually stop breathing,” says Jessica Colyer, MD, a rehabilitation specialist and member of the UC Comprehensive Stroke Center. “Pharmaceutical companies have taken a portion of the protein found in that toxin and use only a fragment for clinical purposes.” The botulinum toxins are approved by the FDA for many uses, including upper-limb spasticity in people who have suffered a stroke; abnormal head position and neck pain in people with cervical dystonia; and chronic migraine in people who suffer 15 or more days a month of pain. Neuroscience specialists also offer the injections off-label in the lower extremities to help patients who have walking impairments after a stroke or spasticity caused by multiple sclerosis (MS) or cerebral palsy. While cosmetic use of botulinum toxin requires tiny injections that paralyze muscles and eliminate wrinkles in the forehead and “crow’s feet” around the eyes, rehabilitation physicians like Dr. Colyer use larger doses to treat spasticity in muscles in the arms, legs and neck. Spasticity is a spinal reflex that fires when it shouldn’t, Dr. Colyer explains. “In a healthy, working brain, the brain sends a signal back down to the muscles to say, ‘This reflex is not needed now; you do not need to be flexing now.’ After a stroke, however, that signal can be cut off. “Stroke survivors start to have an increase in what we call flexor tone,” Dr. Colyer continues. “They curl up and flex their biceps, flex their wrist, or curl their fingers into a flexed fist. These are not functional positions. They prevent you from performing activities of daily living, such as dressing, grooming, brushing your teeth or even putting on deodorant.” Treatment for dystonia & dysphonia The James J. and Joan A. Gardner Family Center for Parkinson’s Disease and Movement Disorders includes a clinic for patients who receive injections of botulinum toxin to treat dystonia and spasticity. The injections can help even in cases where patients experience extreme neck discomfort and deformity, says Alberto Espay, MD, a movement disorders specialist. The Gardner Center also collaborates with otolaryngologists who can provide injections in the vocal cords to improve voice and swallowing problems. Botulinum toxin helps patients with spasmodic dysphonia, also known as laryngeal dystonia, a neurological disorder that affects voice muscles in the larynx, or voice box. It can help patients with adductor spasmodic dysphonia, the most common type of dysphonia, more than 95 percent of the time, according to Sid Khosla, MD, an otolaryngologist and voice specialist at the UC Neurosensory Disorders Center. “Injections also can help about 50 percent of patients with voice tremor,” Dr. Khosla says. “And it can be used to help people who cannot swallow their saliva (hypersalivation) and who experience constant drooling as a result.” Treatment for migraine At the UC Health Headache & Facial Pain Program, botulinum toxin is prescribed for the treatment of chronic migraine. Chronic migraine is one of the most disabling forms of migraine and is diagnosed when patients experience 15 or more days of headache and have a diagnosis of migraine headache. “To treat this condition, 155 units of Botox are injected into 31 sites in the head, neck and shoulders,” explains Vincent Martin, Co-Director of the Headache & Facial Pain Program. “It must be injected every three months, as the effects wear off after several months. Insurance will not pay for the medication unless you have had a poor response to three or more past medications used to prevent migraines.” The average patient experiences an 8- to 10-day reduction in the frequency of headaches per month after administration of botulinum toxin. “It is an excellent therapy for the treatment of chronic migraine and is beneficial in about two out of three patients,” Dr. Martin says. “Those migraines that do occur tend to be far less disabling.” Treatment for multiple sclerosis Dr. Colyer collaborates with the Waddell Center for Multiple Sclerosis to help patients with MS, who can experience spasticity in any of their affected limbs. Patients can have symptoms in the arms similar to those experienced by stroke survivors; they can have spasms in their feet, causing the feet to curl; and they can experience increased tone in their thigh or calf muscles, which prevents normal knee or ankle movements. After getting botulinum toxin injections in their feet flexor muscles, Dr. Colyer says, her patients are able to walk on a normal, flat foot. Injections in the thigh or ankle muscles can eliminate or reduce the spasm and allow for easier walking. Physicians can prescribe other medicines, such as baclofen or tizanidine (Zanaflex), to treat spasticity. But those medications pervade the entire body and cause side-effects, including reduced alertness. The beauty of botulinum toxin, Dr. Colyer says, is that it works only in the muscles that are injected, without creating cognitive side-effects. Botulinum toxin can be injected every three months at most, or four times a year. More frequent injections could lead to the development of antibodies against the protein, which would prevent the medication from being effective. Research is ongoing at various centers, including UC, to determine whether a protein-free toxin formulation may allow more frequent
Targeted Exercise Can Help People with Parkinson’s Disease
Maureen Gartner, MSN, NP-C, in her office at the UC Academic Health Center. By Maureen Gartner, MSN, NP-C Nurse Practitioner Gardner Center for Parkinson’s Disease and Movement Disorders Can exercise help people with Parkinson’s disease? I often hear this question, and the answer is yes! Everyone with Parkinson’s disease is encouraged to exercise. Research conducted during the last 20 years strongly suggests that exercise holds significant quality-of-life benefits for people with Parkinson’s. Studies show that patients’ motor and non-motor scores improve after only 3 months of targeted exercise. Motor scores involve muscle strength, mobility, flexibility, balance, walking, swallowing and speaking. Non-motor scores involve depression, apathy, fatigue and constipation. In short, exercise is a win-win for people with Parkinson’s. Exercise also reduces the risk of other diseases that may develop, including cardiovascular disease, osteoporosis, cognitive impairment and Alzheimer’s disease. What is “targeted” exercise? Targeted exercise for people with Parkinson’s is different from simply getting on a treadmill three days a week. Getting on a treadmill will help your fitness, but by itself it will not help your Parkinson’s. The goal of “targeted” exercise is to challenge your brain to develop or strengthen a variety of neural connections. You can do this by performing different movements rather than a single, repetitive movement. Exercising in a variety of ways will yield the greatest benefits. How often should I exercise, and for how long? Your doctor can recommend a program that is appropriate for you based on your symptoms, fitness level and overall health. Your doctor can recommend how many times a week you should exercise and how long and how intensely you should exercise. Stop exercising if at any time you begin to feel pain or feel sick. What types of exercise are best? An ideal exercise program for people with Parkinson’s is a “targeted” exercise program that includes stretching, strengthening, walking, balance training and aerobic activities that get your heart pumping. It could include time spent on a treadmill or stationary bike. Water aerobics and swimming are other good options. In addition, there are forms of exercise that we don’t always think of as exercise, such as yoga, tai chi and just getting out on the dance floor. You can also exercise your hand muscles and reflexes with the Nintendo Wii, whose games include tennis, bowling, baseball and a balance board. It’s important to stick with your exercise program. Keep in mind that exercise is a way to take control of your Parkinson’s. You cannot always control your disease, but exercise is part of your health that you can control. Who can help create an exercise program that’s right for me? There is a growing number of personal trainers who are knowledgeable about Parkinson’s disease. The local chapter of the American Parkinson’s Disease Association also sponsors multiple exercise classes. These classes are led by personal trainers whose passion is helping people with Parkinson’s disease. Is it safe for me to exercise by myself? To exercise safely is to exercise with a partner or caregiver. Someone should always be with you in case you fall or freeze in place. Wherever you exercise, you should avoid slippery floors, rooms with poor lighting and throw rugs. If you have balance problems, you should exercise in an environment where you can grab onto something if you begin to fall. Nevertheless, there are a few exercises that you might prefer to do alone in the comfort of your home. These include exercises for your facial muscles. You can smile, yawn, shout, sing, make faces in the mirror and make chewing movements to help keep your facial muscles as strong as possible. What are cues and what role do they play in exercise? Cues are hints given by another person, a sound, an image or an object to help you stay balanced or in the right position so that you do not hurt yourself. Cues can be verbal, musical, written (on reminder cards) or visual. For example, if you have freezing of gait, a trainer might put blocks on the floor for you to walk around. The trainer also might also give you verbal cues by saying “BIG STEP” or “BIG STRIDE” to help your brain send that message to your legs. What should I wear when I exercise? Wear loose, comfortable clothing and comfortable shoes. When is the best time to exercise? Exercise when your medicines are working well, not when they are wearing off. I have always been a couch potato. How do I begin? First, be realistic. Check with your doctor and then start slowly. Perhaps you can begin by walking around the block or doing a few crunches while watching TV. Soup cans or soda bottles can be used as simple weights. Next, find an exercise buddy, perhaps your spouse or someone from your support group, neighborhood or church. Be on the lookout for ways to incorporate more activity into your day. Make exercise more enjoyable by listening to music. Remember that exercise can help you live better with Parkinson’s. * * * * * This information is provided by the James J. and Joan A. Gardner Family Center for Parkinson’s Disease and Movement Disorders. It is not intended to replace the advice of your physician. Always consult your physician before starting a new exercise program.
Forget-Me-Not Salon Explores How to Reduce Risk of Cognitive Decline
Drs. John Tew, Jennifer Molano and Joseph Broderick discussed the links between healthy behaviors and cognitive preserve. Photos by Cindy Starr. Healthy aging, compassionate care, the need for new treatments, and the preventive power of diet and exercise were the subjects of an inspiring discussion at the Forget-Me-Not Salon June 19. The event, which drew more than 70 members of the community, benefited the Memory Disorders Center at the University of Cincinnati Neuroscience Institute, a provider of advanced specialty care within UC Health. Cathy Crain, left, and Barbara Gould The Salon, whose organizers included Barbara Gould and Cathy Crain, featured presentations by Joseph Broderick, MD, Director of the UC Neuroscience Institute; Carol Silver Elliott, CEO of Cedar Village Retirement Community; Jennifer Rose Molano, MD, a neurologist and sleep specialist at the UC Memory Disorders Center; and John M. Tew, Jr., MD, Professor of Neurosurgery, Radiology and Surgery at the UC College of Medicine. Dr. Molano explained that the path to cognitive impairment is long and begins far sooner than we might imagine. Alzheimer’s disease, the most common type of dementia, is associated with abnormal processing of two proteins, amyloid and tau, she said. “The abnormal processing of amyloid causes plaques in the brain, and then you get an abnormal process of tau. The tau pathology causes tangles in brain cells, which in turn cause the brain cells to die. “We are finding that amyloid plaque formation is occurring in brain 10 to 15 years prior to the tau-tangle formation in the brain cells,” she continued. “The implication of this is that Alzheimer’s disease does not occur just at that stage when someone comes in to the doctor’s office with memory problems. We’re learning that it goes through a stage without symptoms and a stage we call mild cognitive impairment, when the individual can function without assistance but has issues with thinking that are noticeable when he or she is evaluated. These initial stages occur before the development of dementia, when the patient needs assistance to function due to his or her cognitive difficulties.” The discovery that cognitive decline is a long process underscores the need for better treatments, earlier identification of people who are at risk for developing cognitive impairment, and prevention, Dr. Molano said. Midlife behaviors matter “What people do in midlife is very important and can dictate potentially what will happen to them later,” Dr. Molano said. “Studies have shown that if you have high blood pressure in midlife, if you’re obese in midlife, if you have diabetes in midlife, you are at higher risk for developing mild cognitive impairment or dementia down the road.” Other studies, she added, show that sleep problems also play a role. Conversely, “healthy sleep is just as important as everything else in terms of maintaining your cognitive function.” Dr. Broderick noted that a recent study found that during sleep the brain flushes out toxins that build up during the day. “You’re cleaning house,” he said. “It’s like running a hose to clean out a drain. If you don’t sleep, toxins build up in the brain. Sleep is fundamental.” Optimists and aging Dr. Tew outlined the tenets of healthy aging, including the core messages of Dr. David Snowdon’s landmark book, Aging with Grace: What the Nun Study Teaches Us About Leading Longer, Healthier, and More Meaningful Lives. By studying a population of 678 Catholic sisters, Dr. Tew said, “they discovered how you can predict those who will age without grace. No. 1 is having a positive attitude. They looked back at the entry-level biographies of the nuns — stories they wrote about themselves when they entered the monastery. Those who told stories the best did the best; they aged the best.” Other pillars of healthy aging noted by Dr. Tew are: • Avoid tobacco products • Eat well and avoid highly processed foods, as summed up by author Michael Pollan’s seven words of wisdom: “Eat food. Not too much. Mostly plants.” • Exercise vigorously every day, as exercise promotes the development of new brain cells (neurogenesis) • Stay connected and engaged in your community; live a life of purpose “Ultimately, cognitive preservation involves protection of the blood vessels,” Dr. Tew said. “Having good blood vessels is the most important thing you can do.” He said that orchestra conductors enjoy the greatest longevity of any group of professionals because, “They are moving and exercising with very aggressive use of the brain; it’s the best exercise you can do because you are using muscles and brain cells at the same time.” Genes are not destiny Genes, he said, are not destiny and by themselves will not determine whether you get a disease. He cited the new field of epigenetics, which explores how genes are expressed or suppressed by environmental factors. Dr. Broderick agreed. “Life is a complicated path, and the path is not written. Genes tell us something about the path, but you can get off the road and take a new path. Epigenetics mean that our genes tell us what to do via messengers. There is a process that silences the genes, stops them from talking and sending out the message. Sometimes you can’t silence the genes, but how you care for yourself may change how that gene may express itself. I’m never going to play in NBA – that’s in my genes – but I can play basketball better if I practice. That’s the message. Because most cases of Alzheimer’s disease occur later in life, as opposed to early-onset, there are lots of things that modify it.” Dr. Molano recalled a memorable moment in her training, when one of her professors diagnosed a 93-year-old man with mild cognitive impairment. Perturbed, the man said that he had lived a good life, was a vegetarian, exercised regularly, did yoga, and played bridge three times a week. “If I do all this,” he wondered, “why am I developing mild cognitive impairment now?” Dr. Molano’s colleague answered kindly: “Think about it this way: if you didn’t
Sleep Apnea: A Noisy Stroke Risk Factor that Is Not Always Heard
By Jennifer Rose V. Molano, MD Assistant Professor of Neurology Sleep Specialist, UC Memory Disorders Center “Love your heart. Love your brain,” declares the American Heart Association/American Stroke Association. To love your heart and brain, optimizing your blood pressure, controlling cholesterol levels and maintaining a healthy weight are all important. But there is another risk factor, and that is obstructive sleep apnea. Both men and women are more likely to develop strokes and heart disease if obstructive sleep apnea is left untreated. Obstructive sleep apnea is a disorder that is associated with partial or complete closure of the airways during sleep. This leads to snoring and/or breathing stoppages, known as “apneas.” The effects of obstructive sleep apnea may be obvious and debilitating. Issues such as chronic sleepiness, poor concentration and morning headaches that can interfere with daytime functioning are a few of the symptoms. However, some effects of obstructive sleep apnea are not as obvious. If the airways close during sleep, oxygen levels can drop, and sleep becomes disrupted. Low oxygen levels and sleep disruption lead to poor sleep quality and daytime functioning. And they also cause stress on the body that can create stroke risk factors such as abnormal heart rhythms and increased blood pressure. In stroke survivors, untreated obstructive sleep apnea also places a person at higher risk of having another stroke. If you snore or struggle with daytime sleepiness, or if your breathing stops when you are sleeping, you should be evaluated by a sleep medicine specialist who can determine whether you qualify for a sleep study. During a sleep study, which is performed overnight, a technician monitors your breathing, heart rate and oxygen levels during sleep. Monitoring is required to diagnose obstructive sleep apnea, which is defined by having at least five abnormal breathing events per hour associated with decreased oxygen levels during sleep. The good news is that obstructive sleep apnea is treatable. Continuous positive airway pressure (CPAP) treatment is the first option and works by delivering pressurized room air through a mask to keep the airways open when sleeping at night. Other options, such as sleeping on your side, an oral appliance or surgery can be considered, depending on the degree of obstructive sleep apnea. “Love your heart. Love your brain.” To prevent, treat and beat strokes, also remember to get evaluated for obstructive sleep apnea. Learn more Dr. Jennifer Molano’s profile >> Practicing Good Sleep Hygiene >>
UC Health ALS Clinic Maximizes Quality of Life through Comprehensive Care
Respiratory therapist Ann Compton prepares Thelma, who has ALS,for a pulmonary screening. Photos by Cindy Starr. A diagnosis of ALS, also known as Lou Gehrig’s disease, marks the beginning of one of the most heart-breaking journeys in neurological disease. The path is uniquely difficult for each patient, and the ultimate destination remains, today, immutable. Specialists at the Neuromuscular Center at the University of Cincinnati Neuroscience Institute are working to maximize quality of life for this small population of patients and their families – and creating a foundation for future research studies — with a new comprehensive ALS Clinic. The UC Health ALS Clinic, created with generous support from the Barbara V. Peck and Justin Friedman Fund for research in ALS and UC’s Muscular Dystrophy Association grant, takes place one day each month at the Daniel Drake Center for Post-Acute Care. A patient with ALS typically attends the clinic once every three months for a period of two to three hours. During the visit, the patient and his or her family are situated in a single room, where they are visited by a physician, a social worker and a series of therapists. The goal is to care for all of the patient’s physical, emotional and logistical needs in a single office visit. ALS, or amyotrophic lateral sclerosis, is a progressive neuromuscular disorder involving the loss of nerve cells (neurons) that control the voluntary muscles in the arms, legs and face. These motor neurons are located in the brain, brain stem and spinal cord. As the motor neurons die, muscles waste away. There is no known cure. ALS strikes about 5,000 Americans each year, and 20,000 to 30,000 are living with the disease, according to the National Institute of Neurological Disorders and Stroke (NINDS). The ALS Association’s Central and Southern Ohio Chapter serves about 200 patients from 65 counties at any given time. ALS is more common in men than women and is typically diagnosed in patients between 40 and 60 years of age. About 5 to 10 percent of cases are hereditary. A definite cause of the disease has not been determined. “The ALS Clinic is provides an important service for our patients and families who face the challenge of ALS,” says Robert Neel, MD, above, neuromuscular disorders specialist and the clinic’s director. “It allows us to provide comprehensive care, therapy and counseling for our families.” “What makes this a special population is the severity of the disease and how rapidly it strikes,” says Paige Thomas, PT-MSR, NCS, MHA, at right, Manager of Outpatient Therapeutic Services. “Nevertheless, there is still so much we can do for our patients to maintain their strength, function and quality of life.” The ALS Clinic, which began in February 2013, is also establishing a framework for clinical trials, which will be supported by the Peck-Friedman Fund. The UC Neuroscience Institute’s standing as a NINDS-funded Network for Excellence in Neuroscience Clinical Trials (NEXT) means that the ALS Clinic is poised to participate in future national clinical trials of ALS therapies. Potential studies, now pending, would not be possible without the clinic, Dr. Neel says. Patients at the ALS Clinic typically begin with a visit from Dr. Neel, who assesses their physical and mental condition as well as topics ranging from home health support, caregiver support and hospice care. “I also monitor depression, if they are having those issues,” Dr. Neel says. “Patients with ALS experience a pseudo bulbar affect. Their emotional brakes are off, and they cry when they don’t need to and laugh when they don’t need to. That’s one of the things we deal with. There are medications that can help. It is liberating for them to understand this; if someone blames them for it, they need to say, ‘It’s part of my disease. You wouldn’t blame me for my arm going weak.’ ” Thelma, a retired businesswoman and current resident of Warren County, Ohio, was among the patients at the ALS Clinic on a recent morning. She saw Dr. Neel and as well as several therapists. Thelma’s respiratory therapist, Ann Compton, performed a pulmonary function test, which helped Dr. Neel gauge where Thelma is in the course of the disease. An occupational therapist, Connie Buda, tested Thelma’s hand strength. Ms. Buda works with patients on functional tasks that most of us take for granted — activities of daily living such as shaving, dressing, and using the phone or keyboard. She also can administer driving tests and assess a patient’s capabilities in a workshop kitchen. Thelma visited with Ms. Thomas, a physical therapist, who focused on her physical strength. “I work on patients’ gross motor strength, their walking and their balance,” Ms. Thomas says. “I can provide braces, walkers, wheelchairs and other medical equipment to help them maintain their independence.” A speech therapist is also available to assist patients with issues related to speech, eating, nutrition and swallowing. When patients reach an advanced stage of disease, the muscles necessary to formulate sounds and to swallow are no longer strong enough to do so. At this point patients are sometimes provided with speech devices, says Courtney Anness, a speech therapist. “We look at using an iPad when a person’s speech output is no longer intelligible,” she says. “When they can no longer access it with their hand, we move to a communication device that they can control by using their eyes, or with a head plate and reflective sticker that we put between their eyebrows or on their eyeglasses. If they move their head slightly, they can activate the screen. Each device is specific to the patient; words and phrases are preprogrammed to express basic wants and needs, such as, I love you, can you readjust me in bed, who is coming to visit today?” Thelma’s final visitor was Yvonne Dressman, LSW, right, a social worker and Care Services Coordinator for the ALS Clinic. Ms. Dressman assists patients and families with social issues, including home health care, preparing a power of attorney, and inevitable end-of-life
Expert Seeks Improved Monitoring of ‘Brain Tsunamis’ after TBI
Dr. Jed Hartings, a former Major in the U.S. Army’s Medical Service Corps, has made the study of spreading depolarizations his life’s work. Photo by Cindy Starr. Jed Hartings, PhD, Research Associate Professor at the UC Neuroscience Institute, is among the world’s leaders in the research of brain waves known as spreading depolarizations. These electrical disturbances spread like tsunamis through a brain injured by stroke or trauma. And like tsunamis, they cause destruction. “Compared to normal brain waves, these really are tsunamis,” Dr. Hartings says. “They are 5 to 10 times the size of epileptic seizure discharges. Although they are very focal at any given time — with a spatial wavelength of just a centimeter of brain tissue — they spread widely through an injured lobe of the brain.” Listen to a Brain Tsunami >> Anyone who has suffered a migraine headache might have actually experienced a spreading depolarization. “In an awake individual who is suffering a migraine, a single wave can cause blindness on one side or can cause your arm or face to go numb,” Dr. Hartings says. “Imagine what effect 20 to 50 of these waves will have in a comatose patient who has suffered a traumatic brain injury.” Dr. Hartings, a founding member of the international organization COSBID (Co-Operative Study on Brain Injury Depolarizations), has devoted his career to understanding, monitoring and seeking an effective treatment for this pathologic brain activity. “Our lab and our leadership have generated the evidence for the role of spreading depolarizations in traumatic brain injury worldwide,” Dr. Hartings says. “We really characterized this phenomenon and this disease.” Dr. Hartings began by investigating spreading depolarizations as being possibly important. “Today,” he says, “we know they are important; we know they are relevant to patients’ outcomes; and we know that they occur in many patients.” In 2011 Dr. Hartings was the lead author of two benchmark papers about spreading depolarizations, published in the prestigious journals Brain and Lancet Neurology. Dr. Hartings and his colleagues showed through their research that the depolarizations are not only linked to worse outcomes, they also cause worse outcomes. Stopping them with medical treatment, they reported, could prevent many victims of major head injury from suffering additional brain damage. The research was funded largely by a four-year $1.96 million grant awarded through the U.S. Department of Defense’s Psychological Health and Traumatic Brain Injury (PH/TBI) Research Program (formerly known as the Post Traumatic Stress Disorder/TBI Research Program). The topic of spreading depolarizations has been of keen interest to the U.S. military since the emergence of head injuries as the signature wound of the wars in Iraq and Afghanistan. Results of a more detailed study, also funded by the U.S. Department of Defense, are on the horizon. The five-year investigation involving 140 patients at five academic health centers will provide full clinical details about the occurrence of depolarizations and what sub-types of injury the depolarizations are associated with. Even more dramatic findings are on the way. Although Dr. Hartings and his co-investigators currently monitor depolarizations by placing an electrode strip onto the brain of patients who undergo surgery, their newest research involves exploring different types of monitors that do not have to be placed directly on the brain. Such monitoring would benefit patients who have suffered brain injury but do not require surgery. “One of our main objectives going forward is to develop techniques for measuring spreading depolarizations non-invasively, using a more traditional electroencephalograph, or EEG,” Dr. Hartings says. “Currently we can record them only from electrodes placed directly on the brain, which really limits us to studying maybe 5 or 10 percent of patients with traumatic brain injury. Ultimately, we need to translate that knowledge into a tool that can be used in a clinical, bedside device by any clinician.” Dr. Hartings has published more than 40 peer-reviewed journal articles and has one patent and two invention disclosures to his credit. — Cindy Starr