UCLA Neurology Newsletter, Spring 2006 - NEUROLOGY


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UCLA Neurology Newsletter, Spring 2006 - NEUROLOGY

  1. 1. Headache Program Bringing Relief to Widespread, Poorly Understood Problem vol.2, no.1 NEUROLOGY UCLA Neurology Newsletter ew medical disorders are as common, or cause as much disability, as headache. Hundreds of millions of individuals worldwide – including an estimated one in four women and one in 10 men – suffer from migraines. And yet, despite the staggering social and economic societal costs of migraine (hundreds of millions of days of disability and tens of billions of dollars in employer costs per year), it remains poorly understood. Consequently, many patients are unable to control their headaches with current treatments. “Headache has been underappreciated as a basic science and clinical problem,” says Andrew Charles, M.D., professor in UCLA’s Department of Neurology. “When you consider its prevalence and the amount of suffering and disability it causes, funding for headache research has been trivial compared with funding to study other medical disorders.” Only a handful of programs in the country combine multidisciplinary research, training, and therapy in headache. One of those is the UCLA Headache Research and Treatment Program, under the direction of Dr. Charles. The program is dedicated to increasing the understanding of the molecular and cellular basis of headaches – including genetic, hormonal, and chemical influences – and applying that knowledge to optimizing treatment. Physicians and scientists are trained to have a better grasp of the basic and clinical aspects of headache, and new therapeutic approaches are being studied at the same time that a multidisciplinary team treats headache patients with both pharmaceutical and non- pharmaceutical strategies. The research effort is proceeding on several fronts. Genetics is believed to play an important role in some of the most common forms of headache, including migraines, but for the most common types of migraine, the responsible genes have not yet been identified. Investigators in the UCLA Headache Research and Treatment Program are homing in on the genes suspected to be involved, and studying the functional consequences of genetic changes that might be related to headache disorders. Researchers are also seeking a better understanding of the basic physiological mechanisms of headaches. Migraines are associated with a variety of significant changes in the electrical activity of the brain, which can be documented with sophisticated electrophysiological recording techniques. The program’s researchers have developed a high- resolution technique that visualizes a process believed to underlie migraines in mice. “In the living mouse, we can now visualize a spreading wave of brain activation that we think is a fundamental basis for migraines,” Dr. Charles says. “We can use this model to investigate genes and hormones that may influence migraine, and to identify therapeutic approaches to block the migraine before it starts or treat it once it begins.” A study on the role of female hormones in headache is yielding interesting results, Dr. Charles notes. Other studies are investigating the pharmacology of headache, in an effort to identify drug treatments. Human functional imaging techniques are yielding exciting new findings, Dr. Charles says, by providing a window into which scientists can view the dramatic, dynamic changes in the brain activity of headache patients with unprecedented resolution. UCLA’s internationally leading functional imaging program is also a boon to the Headache Program’s efforts to develop experimental models to study migraines. “There are a variety of fairly simple changes people can make to help reduce the frequency and severity of headaches,” says Dr. Charles. “We Andrew Charles, M.D. Headache Program Director
  2. 2. 2 PartnersinDiscovery Production Manager: Garnet Johnson Writer/Editor: Dan Gordon Designer: [Maggie] Huyentrang T. Nguyen Photographer: Reed Hutchinson Inside this Issue... 5 Family Establishes Center to Find Answers for Parkinson's 6 Introducing Allan D. Wu, M.D. 7 4 Donor Recognition Kudos Epilepsy Alternatives Headache Program Bringing Relief to Widespread, Poorly Understood Problem [continued] help patients identify potential triggers and work to avoid those triggers.” A central theme for the headache patient should be consistency, he explains. Irregular sleep and exercise, skipped meals, unbalanced diets and fluctuating caffeine levels can all trigger headaches; patients are advised to keep these lifestyle elements as constant as possible. Neurologists in the program also help patients find the right medication or combination of medications to best treat their specific type of headache. The program has also begun to establish clinical trials to test new therapies for headache patients who have failed to find relief from existing treatments. Some of these new therapies have been identified by studies done in Dr. Charles’s laboratory. In addition to providing high- quality patient care, the UCLA Headache Research and Treatment Program aims to educate the broader community of physicians in both basic and specialized headache treatment. A fellowship program is training future headache specialists, and several outreach programs are educating community physicians in current headache diagnosis and management. Headaches are often improperly diagnosed and treated, even in the medical community, Dr. Charles notes. For example, many patients are misdiagnosed as having sinus headaches when they actually are suffering from migraines; as a result, the medications prescribed to treat them are less than optimal. “The treatment of headache in the community varies greatly,” says Dr. Charles. “We’re trying to formalize the understanding of headache so that there’s a higher standard of care.” As more is learned about migraines, experts are beginning to suspect that they may be a fundamental property of the human nervous system, with genetic and environmental factors affecting the threshold beyond which individuals will experience them. “That means not only that migraine is an extremely common disorder with a huge impact on quality of life and disability worldwide,” says Dr. Charles, “but also that a better understanding of migraine may lead to a better understanding of the basic function of the brain. This understanding may provide insight into other neurological disorders, from stroke and epilepsy to brain cancer and brain trauma.”
  3. 3. 3 PartnersinDiscovery Letter from the Chair his year marks the 50th Anniversary of the UCLA Department of Neurology. While we in the department are proud of all that has been accomplished in these last five decades, we have chosen to celebrate this anniversary not by looking back, but rather by looking forward. We have committed an entire year of activities to just this purpose and have named the events of the year 50 and Forward. The most important aspect of this anniversary year will be a campaign with you, our Partners in Discovery, to continue to build our relationship with individuals in the community and the private sector to raise public awareness and unrestricted funds that will help support research, education and patient care for our mission – namely, the quest to help understand diseases of the nervous system and treat patients with neurological disorders. Events will take place throughout the year, and an important aspect of these activities will be to grow the ranks of the Partners in Discovery. Everyone has something to contribute. For some it is their time, for others it is funding and, for all of us, our expertise. Together we will make this year a landmark and a turning point. It is likely that in the next three to four years, we will learn more about the normal functions of the nervous system and disorders that affect it than we have learned in the last 50. Advanced technologies and new insights into the function of the brain, spinal cord and nerves are accelerating at an unprecedented rate. We are at the point of converting promises of progress to deliverable treatments for our patients. Originally a division of the Department of Medicine at UCLA, Neurology became a department through the foresight and strong leadership of its first chairman, Augustus S. Rose, M.D. Dr. Rose, with five other faculty, launched an effort to create a department that would serve patients with neurological disorders and provide research leading to better treatments and, ultimately, cures for these disorders. The department has grown over the years under the able leadership of two subsequent former chairs, Richard Walter, M.D., and Robert Collins, M.D., to the point where we now have more than 100 faculty and nearly 200 trainees. For the last three years, the department has consistently been number one or number two in research funding from the National Institutes of Health. This is perhaps the most rigorous metric of the quality and quantity of scientific research that we have in the United States. 50 and Forward will be a critical aspect of accelerating this process at UCLA and, with your commitment and loyal participation, seeing the fruits of 50 years of effort delivered directly to patients with neurological disorders – not just here at UCLA, but throughout the world. Dear Friends, John Mazziotta, M.D., Ph.D. Chair, Department of Neurology Stark Professor of Neurology
  4. 4. 4 PartnersinDiscovery Promising Alternatives Emerging for Epilepsy Patients Not Helped by Drugs orty percent of the 2.5 million people in the United States with epilepsy have poorly controlled seizures. Recurrent seizures lead to social isolation, unemployment, inability to drive, and injuries from falls and burns, as well as drowning. Despite the introduction of multiple new antiepileptic drugs since the 1990s, as many as one million individuals with epilepsy across the country fail to benefit from drug treatment. While surgery can be effective, many patients are either not ideal candidates or lack access to one of the few specialized epilepsy centers, such as UCLA, where surgery is offered. “Most people with chronic epilepsy who have continuing seizures are drug-resistant,” says Christopher DeGiorgio, M.D., Professor-in- Residence of Neurology at UCLA. “Even with the new drugs, at least half of these individuals are not being helped, and only 5-10 percent of those who take the newer drugs become seizure-free. In addition, anti-seizure drugs can have significant side effects on behavior, thinking, and alertness. Women taking anti-seizure drugs and their unborn children are at special risk because of the effect of these drugs on fetal growth and development. For all of these reasons, we need to find non- drug alternative treatments.” The first is a new non-drug therapy developed for use in humans by Dr. DeGiorgio and Dr. Alan Shewmon, in collaboration with Dr. Todd Whitehurst from Advanced Bionics, Inc., called trigeminal nerve stimulation (TNS). TNS uses an implantable “brain pacemaker” to stimulate a nerve in the face and forehead that extends into the brain, in an effort to interrupt the process of seizure activity. TNS has two potential advantages over the commercially available vagus nerve stimulator (VNS), Dr. DeGiorgio notes. “The vagus nerve stimulator is expensive, and we can’t predict who will respond to it until after it is surgically implanted,” he explains. “With TNS, we can first test an individual’s response using an inexpensive neurostimulator that patients wear on their belt and electrodes taped to their face. If it proves beneficial, then it could be surgically implanted under the skin.” In addition, while VNS stimulates only one side of the brain, TNS stimulates both sides, he notes. The concept, originally tested in animal studies by researchers at Duke University, was developed and used for the first time in humans by Dr. DeGiorgio’s group in a recently completed pilot study. Of the seven people who completed at least three months wearing the external stimulator, four experienced a 50 percent or better reduction in seizure frequency; after six months, five had such a reduction. Dr. DeGiorgio is currently enrolling patients in a follow-up study that will seek to extend the findings to 25 patients. A third study will examine the impact of implanting TNS with an electrode under the skin (just beneath the eyebrow) of patients who respond to the external stimulator. Equally intriguing is a new study being launched by Dr. DeGiorgio’s group to examine the potential for omega-3 fatty acids, the main component of fish oil, to lower epilepsy patients’ risk of sudden death and reduce seizure frequency and severity. The risk of sudden death for people with epilepsy is 24 times higher than that of the general population. Previous research by Dr. Thomas Henry, a former fellow of the UCLA Epilepsy Program, has found that people with epilepsy have low levels of omega-3 fatty acids. Studies have also found that omega-3s have many health benefits – including reducing the risk of sudden death in heart disease patients. In addition, animal studies have found that omega-3 fatty acids, which block sodium channels in both the heart and the brain, not only stabilize heart rhythms, but can also reduce seizure activity. Given the strength of the animal data, Dr. DeGiorgio is starting a pilot study for people with poorly controlled epilepsy to determine whether omega- 3 fatty acids reduce the risk of sudden death and their seizure severity and frequency. “Even if we only find a reduced risk of sudden death, that would be a major breakthrough,” says Dr. DeGiorgio and his colleagues are currently pursuing two such alternatives, both of which appear promising.
  5. 5. Epilepsy [continued] Chen Family Establishes Center to Find Answers for Parkinson's 5 PartnersinDiscovery hen Fu-Hsing Chen was diagnosed with Parkinson’s disease, his priorities changed. The successful entrepreneur, along with his wife, Jyu-Yuan, vowed to do something that would help others who were also struggling with the debilitating disorder. In June 2004, they donated funds to establish the Fu-Hsing and Jyu- Yuan Chen Center for Translational Research in Parkinson’s Disease, based in the UCLA Department of Neurology, and to recruit two of the top clinician researchers in the field. “The Parkinson’s diagnosis really came out of the blue, and my father decided to shift his focus from business to trying to help this cause,” says Frank Chen, son of Fu- Hsing and Jyu-Yuan who, along with his brother, is a UCLA alumnus. He notes that the family considered many institutions throughout the country before deciding that UCLA offered the potential for the most comprehensive program – where basic researchers and clinicians could work together to translate laboratory findings into better treatments, drawing on the vast resources and expertise within the Department of Neurology and across the UCLA campus. “My father was impressed with UCLA’s emphasis on speeding up the process of applying the latest research findings to patient care,” Frank Chen says. Researchers at the Chen Center are fighting Parkinson’s disease on many fronts, from exploring surgical solutions and environmental causes to investigating the potential for using healthy stem cells to replace damaged cells. “My husband was suffering, and he knew a lot of other people were going through the same thing,” says Jyu-Yuan Chen. “We recognized that UCLA was an excellent place for a center where ideas could be exchanged and everyone’s input could be brought together toward solving this disease. It has been very gratifying to see that begin to occur.” Dr. DeGiorgio. “But we also know that the low levels of omega-3 among people with epilepsy can have many negative health effects. And we have preliminary data that increasing their omega-3 levels improves thinking processes and memory, and may reduce seizure severity. If this hypothesis is borne out in further research, omega-3s could be to people with epilepsy what folic acid has been for pregnant women – a low-cost supplement that is safe and has minimal side effects.” Christopher DeGiorgio, M.D., Professor-in-Residence of Neurology Executive Vice Chair of Clinical Affairs Fu-Hsing and Jyu-Yuan Chen
  6. 6. 6 PartnersinDiscovery Introducing Allan D. Wu, M.D. llan Wu, M.D., joined the UCLA Department of Neurology in the Division of Movement Disorders last August, bringing to UCLA his clinical expertise in Parkinson’s disease, dystonia, tremor and botulinum toxin injections. Dr. Wu is also interested in using research methods such as 3-D movement analysis, transcranial magnetic stimulation (TMS) and functional MRI (fMRI) to better understand the problems that affect patients with movement disorders. Dr. Wu has a B.S. in electrical bioengineering from UC Berkeley, received his M.D. degree from Johns Hopkins School of Medicine and completed neurology residency at the Harvard Longwood Neurology Training Program in Boston. Following residency, he completed two fellowships: first, in neuromuscular disease electromyography at the Lahey Clinic in Burlington, Mass.; and second, in movement disorders at USC. Dr. Wu remained at USC as a member of the clinical faculty for four years before coming to UCLA. Dr. Wu’s research interests focus on how the brain controls the arm and hand in making movements to point at, reach toward, or hold everyday objects. Understanding how this control is impaired in patients with movement disorders such as Parkinson’s disease and dystonia can provide insights into how rehabilitation treatments can help movement symptoms in these patients. One of Dr Wu’s research techniques is TMS, a safe, noninvasive and relatively painless method of stimulating the brain in volunteers with an insulated electromagnetic coil. This brain-mapping method is used to examine the role of various brain regions during the planning or execution of routine arm movements. In conjunction with fMRI, TMS is used to develop maps of the brain that show how movement disorders can affect the brain and cause movement problems in patients. TMS has been available at UCLA since the founding of the Brain Mapping Center, but mostly as a brain-mapping tool in neurologically normal subjects. As associate director of the center’s TMS Laboratory, Dr. Wu joins the director, Dr. Marco Iacoboni, in further developing TMS resources at UCLA. Dr. Wu hopes to expand TMS research at UCLA to patients with movement disorders and to eventually explore the potential of therapeutic uses of TMS. Already, planning is underway for projects that will study TMS as a potential treatment for some of the symptoms in Parkinson’s disease or dystonia. “I am driven by the question of how the nervous system controls movement,” Dr. Wu explains. “Coming to UCLA and this department has given me a tremendous opportunity to pursue this question, to better understand what occurs within the brain of patients who have movement disorders and to help design therapies to improve patients’ symptoms.” Allan D. Wu, M.D. Dr. Wu applying TMS to a volunteer in a study of visual perception Analysis of TMS induced muscle twitches Example of using TMS to study reaction time (RT)
  7. 7. 7 PartnersinDiscovery Kudos Andrew Charles, M.D., has been named by The American Headache Society as the recipient of the 2006 Seymour Solomon Presidential Lecture award. This prestigious award is highlighted by a lecture that provides an update on Dr. Charles’ work on cortical spreading depression and how it will lead to a better understanding of the physiological underpinnings of the migraine aura and influence progression in this area of scientific inquiry. Daniel Geschwind, M.D., Ph.D., has been appointed to the Gordon and Virginia MacDonald Endowed Chair in Human Genetics. This endowed chair is intended for a scientist whose research focuses on neurogenetics. Dr. Geschwind’s focus within neurogenetics includes both neurodevelopmental and neurodegenerative areas. John C. Mazziotta, M.D., Ph.D., was featured in the October 24, 2005 issue of Time. Dr. Mazziotta's project, the International Consortium for Brain Mapping, is a 12-year collaborative effort to create an atlas of the human brain. Coordinated by Drs. Mazziotta and Arthur Toga, this project will result in an atlas to be released online in 2007 and stored at UCLA using data storage robots with 1 petabyte of data capacity, which is equivalent to a book with 250 billion pages. The atlas will benefit doctors, who will soon be able to compare a patient's brain to that of 7,000 normal brains to locate a problem area. Jeffrey Saver, M.D., published in Stroke: Journal of the American Heart Association his research synthesizing new brain-imaging and cell-counting techniques to quantify nerve cell loss in stroke. He found that a stroke victim loses 1.9 million neurons every minute in which treatment is not delivered. The calculations were for the most common type of stroke, an ischemic stroke, caused when a blood clot blocks blood flow to the brain. Rhonda Voskuhl, M.D., director of the UCLA Multiple Sclerosis Program, and her colleagues were awarded the Collaborative Multiple Sclerosis Research Center Award by the National Multiple Sclerosis Society. This $825,000 award is given over the next five years and is one of only three awards given to universities in the United States. The work of Dr. Voskuhl and her interdisciplinary team aims to find ways to protect brain tissues and preserve function in persons with MS. DirecTV raised $255,000 for the UCLA Multiple Sclerosis Program at the ninth annual DirecTV Charity Golf Classic held at the Rio Secco Golf Course in Las Vegas January 4. John Suranyi, president of sales and service for DirecTV, presented the check to Dr. John Mazziotta, chair of the UCLA Department of Neurology, and Dr. Rhonda Voskuhl, director of the UCLA MS Program. This event has grown increasingly successful since its inception, raising more than $1 million to assist the UCLA MS Program in its efforts to develop new therapies and provide excellent care for patients with MS. Donor Recognition
  8. 8. Neurology Programs and Program Directors NON-PROFIT ORGANIZATION U.S POSTAGE PAID UCLA United in Purpose Partners in Discovery To join Partners in Discovery contact: Garnet Johnson [310] 206 5769 or gajohnson@mednet.ucla.edu Healthcare Department of Neurology Attention: Garnet Johnson Reed Neurological Research Center 710 Westwood Plaza Los Angeles, CA 90095 Spring 2006 Neurogenetics Daniel Geschwind, M.D., Ph.D. Neuromuscular Diseases Michael Graves, M.D. Neuro-otology Robert Baloh, M.D. Neuro-rehabilitation Bruce Dobkin, M.D. Sleep Frisca Yan-Go, M.D. Stroke Jeffrey Saver, M.D. Health Services Barbara Vickrey, M.D., M.P.H. LONI Arthur Toga, Ph.D. Movement Disorders Jeff Bronstein, M.D., Ph.D. Multiple Sclerosis Rhonda Voskuhl, M.D. Neuro-AIDS Elyse Singer, M.D.    Neurodegeneration Marie-Francoise Chesselet, M.D., Ph.D. Alzheimer's Disease Jeffrey Cummings, M.D. Brain Mapping John Mazziotta M.D., Ph.D. Brain Tumor Timothy Cloughesy, M.D. Education Perrin Pleninger, M.D. Epilepsy Jerome Engel, M.D., Ph.D. Headache Andrew Charles, M.D.