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  • 1. NEUROLOGY UCLA Neurology NewsletterHeadache Program Bringing Relief vol.2, no.1to Widespread, Poorly Understood Problem ew medical disorders are as also seeking a better understanding of common, or cause as much the basic physiological mechanisms of disability, as headache. Hundreds headaches. Migraines are associated of millions of individuals worldwide with a variety of significant changes – including an estimated one in four in the electrical activity of the brain, women and one in 10 men – suffer which can be documented with from migraines. And yet, despite the sophisticated electrophysiological staggering social and economic societal recording techniques. The program’s costs of migraine (hundreds of millions researchers have developed a high- of days of disability and tens of billions resolution technique that visualizes a of dollars in employer costs per year), process believed to underlie migraines it remains poorly understood. in mice. “In the living mouse, we can Consequently, many patients are unable now visualize a spreading wave of to control their headaches with current brain activation that we think is a treatments. fundamental basis for migraines,” Dr. “Headache has been Charles says. “We can use this model underappreciated as a basic science to investigate genes and hormones that and clinical problem,” says Andrew may influence migraine, and to identify Charles, M.D., professor in UCLA’s therapeutic approaches to block the Department of Neurology. “When you migraine before it starts or treat it once consider its prevalence and the amount Andrew Charles, M.D. it begins.” A study on the role of female of suffering and disability it causes, Headache Program Director hormones in headache is yielding funding for headache research has been interesting results, Dr. Charles notes. trivial compared with funding to study Other studies are investigating the other medical disorders.” same time that a multidisciplinary team pharmacology of headache, in an effort Only a handful of programs in the treats headache patients with both to identify drug treatments. country combine multidisciplinary pharmaceutical and non- Human functional imaging research, training, and therapy in pharmaceutical strategies. techniques are yielding exciting new headache. One of those is the UCLA The research effort is proceeding findings, Dr. Charles says, by providing Headache Research and Treatment on several fronts. Genetics is believed a window into which scientists can Program, under the direction of Dr. to play an important role in some of view the dramatic, dynamic changes Charles. The program is dedicated to the most common forms of headache, in the brain activity of headache increasing the understanding of the including migraines, but for the most patients with unprecedented resolution. molecular and cellular basis of common types of migraine, the UCLA’s internationally leading headaches – including genetic, responsible genes have not yet been functional imaging program is also a hormonal, and chemical influences – identified. Investigators in the UCLA boon to the Headache Program’s efforts and applying that knowledge to Headache Research and Treatment to develop experimental models to optimizing treatment. Physicians and Program are homing in on the genes study migraines. scientists are trained to have a better suspected to be involved, and studying “There are a variety of fairly simple grasp of the basic and clinical aspects the functional consequences of genetic changes people can make to help of headache, and new therapeutic changes that might be related to reduce the frequency and severity of approaches are being studied at the headache disorders. Researchers are headaches,” says Dr. Charles. “We
  • 2. Headache Program Bringing Relief to Widespread, Poorly Understood Problem [continued] help patients identify potential triggers Program aims to educate the and work to avoid those triggers.” A broader community of central theme for the headache patient physicians in both basic should be consistency, he explains. and specialized headache Irregular sleep and exercise, skipped treatment. A fellowship meals, unbalanced diets and fluctuating program is training future caffeine levels can all trigger headaches; headache specialists, and patients are advised to keep these several outreach lifestyle elements as constant as programs are educating possible. Neurologists in the program community physicians also help patients find the right in current headache medication or combination of diagnosis and medications to best treat their specific management. type of headache. The program has also Headaches are often begun to establish clinical trials to test improperly diagnosed new therapies for headache patients and treated, even in the who have failed to find relief from medical community, existing treatments. Some of these new Dr. Charles notes. For therapies have been identified by studies example, many patients done in Dr. Charles’s laboratory. are misdiagnosed as In addition to providing high- having sinus headaches quality patient care, the UCLA when they actually are Headache Research and Treatment 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 worldwide,” says they may be a fundamental property of Dr. Charles, “but also that the human nervous system, with genetic a better understanding of and environmental factors affecting the migraine may lead to a better threshold beyond which individuals understanding of the basic function of will experience them. “That means not the brain. This understanding may only that migraine is an extremely provide insight into other neurological common disorder with a huge impact disorders, from stroke and epilepsy to on quality of life and disability brain cancer and brain trauma.”Partners in Discovery 4 Epilepsy Alternatives 6 Introducing Production Manager: Garnet Johnson Inside Allan D. Wu, M.D. this Writer/Editor: Dan Gordon Issue... Designer: [Maggie] Huyentrang T. Nguyen 5 Family Establishes Center to 7 Donor Recognition Find Answers for Parkinsons Kudos Photographer: Reed Hutchinson 2
  • 3. Letter from the Chair Dear Friends, his year marks the 50th understand diseases of the nervous Anniversary of the UCLA system and treat patients with Department of Neurology. neurological disorders. While we in the department are proud Events will take place throughout of all that has been accomplished in the year, and an important aspect of these last five decades, we have chosen these activities will be to grow the to celebrate this anniversary not by ranks of the Partners in Discovery. looking back, but rather by looking Everyone has something to contribute. forward. We have committed an entire For some it is their time, for others it year of activities to just this purpose 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 leadership of two subsequent former of the nervous system chairs, Richard Walter, M.D., and and disorders that Robert Collins, M.D., to the point affect it than we have where we now have more than 100 learned in the last 50. faculty and nearly 200 trainees. Advanced For the last three years, the technologies and new department has consistently been insights into the number one or number two in research function of the brain, funding from the National Institutes spinal cord and nerves of Health. This is perhaps the most are accelerating at an rigorous metric of the quality and unprecedented rate. quantity of scientific research that we We are at the point of have in the United States. 50 and converting promises Forward will be a critical aspect of of progress to accelerating this process at UCLA and, deliverable treatments with your commitment and loyal for our patients. participation, seeing the fruits of 50 Originally a years of effort delivered directly to division of the patients with neurological disorders – Department of not just here at UCLA, but throughout Medicine at UCLA, the world. and have named the events of the year Neurology became a department 50 and Forward. The most important through the foresight and strong aspect of this anniversary year will be leadership of its first chairman, Partners in Discovery a campaign with you, our Partners in Augustus S. Rose, M.D. Dr. Rose, with Discovery, to continue to build our five other faculty, launched an effort relationship with individuals in the to create a department that would serve community and the private sector to patients with neurological disorders raise public awareness and unrestricted and provide research leading to better funds that will help support research, treatments and, ultimately, cures for John Mazziotta, M.D., Ph.D. education and patient care for our these disorders. The department has Chair, Department of Neurology mission – namely, the quest to help grown over the years under the able Stark Professor of Neurology 3
  • 4. Promising Alternatives Emerging for Epilepsy Patients Not Helped by Drugs orty percent of the 2.5 million pacemaker” to stimulate a nerve in the patients. A third study will examine people in the United States face and forehead that extends into the the impact of implanting TNS with an with epilepsy have poorly brain, in an effort to interrupt the electrode under the skin (just beneath controlled seizures. Recurrent process of seizure activity. TNS has the eyebrow) of patients who respond seizures lead to social isolation, two potential advantages over the to the external stimulator. unemployment, inability to drive, and commercially available vagus nerve Equally intriguing is a new study injuries from falls and burns, as well stimulator (VNS), Dr. DeGiorgio notes. being launched by Dr. DeGiorgio’s as drowning. Despite the introduction “The vagus nerve stimulator is group to examine the potential for of multiple new antiepileptic drugs expensive, and we can’t predict who omega-3 fatty acids, the main since the 1990s, as many as one million will respond to it until after it is component of fish oil, to lower epilepsy individuals with epilepsy across the surgically implanted,” he explains. patients’ risk of sudden death and country fail to benefit from drug “With TNS, we can first test an reduce seizure frequency and severity. treatment. While surgery can be individual’s response using an The risk of sudden death for people effective, many patients are either not inexpensive neurostimulator that with epilepsy is 24 times higher than ideal candidates or lack access to one patients wear on their belt and that of the general population. Previous of the few specialized epilepsy centers, electrodes taped to their face. If it research by Dr. Thomas Henry, a such as UCLA, where surgery is proves beneficial, then it could be former fellow of the UCLA Epilepsy offered. surgically implanted under the skin.” Program, has found that people with “Most people with chronic In addition, while VNS stimulates only epilepsy have low levels of omega-3 epilepsy who have continuing seizures one side of the brain, TNS stimulates fatty acids. Studies have also found are drug-resistant,” says Christopher both sides, he notes. that omega-3s have many health DeGiorgio, M.D., Professor-in- The benefits – Residence of Neurology at UCLA. concept, including “Even with the new drugs, at least half originally reducing the of these individuals are not being tested in risk of sudden helped, and only 5-10 percent of those animal death in heart who take the newer drugs become studies by disease seizure-free. In addition, anti-seizure researchers patients. In drugs can have significant side effects at Duke addition, on behavior, thinking, and alertness. University, animal studies Women taking anti-seizure drugs and was have found their unborn children are at special risk developed that omega-3 because of the effect of these drugs on and used fatty acids, fetal growth and development. For all for the first which block of these reasons, we need to find non- time in sodium drug alternative treatments.” humans by channels in both the heart and the brain, Dr. DeGiorgio and his not only colleagues are currently stabilize heart pursuing two such alternatives, Dr. DeGiorgio’s group in a rhythms, but can also reduce seizure . study. Of the seven people both of which appear promising recently completed pilot activity. Given the strength of the animalPartners in Discovery who completed at least three data, Dr. DeGiorgio is starting a pilot The first is a new non-drug therapy months wearing the external stimulator, study for people with poorly controlled developed for use in humans by Dr. four experienced a 50 percent or better epilepsy to determine whether omega- DeGiorgio and Dr. Alan Shewmon, in reduction in seizure frequency; after 3 fatty acids reduce the risk of sudden collaboration with Dr. Todd Whitehurst six months, five had such a reduction. death and their seizure severity and from Advanced Bionics, Inc., called Dr. DeGiorgio is currently enrolling frequency. “Even if we only find a trigeminal nerve stimulation (TNS). patients in a follow-up study that will reduced risk of sudden death, that TNS uses an implantable “brain seek to extend the findings to 25 would be a major breakthrough,” says 4
  • 5. Epilepsy [continued] Chen Family Establishes Center to Find Answers for Parkinsons hen Fu-Hsing Chen was investigating the potential for using diagnosed with healthy stem cells to replace Parkinson’s disease, his damaged cells. 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. Dr. DeGiorgio. “But we also know “The Parkinson’s that the low levels of omega-3 among diagnosis really came out of people with epilepsy can have many the blue, and my father decided negative health effects. And we have to shift his focus from business preliminary data that increasing their to trying to help this cause,” omega-3 levels improves thinking says Frank Chen, son of Fu- processes and memory, and may Hsing and Jyu-Yuan who, reduce seizure severity. If this along with his brother, is a Fu-Hsing and Jyu-Yuan Chen hypothesis is borne out in further UCLA alumnus. He notes that the research, omega-3s could be to people family considered many institutions with epilepsy what folic acid has been throughout the country before “My husband was suffering, and for pregnant women – a low-cost deciding that UCLA offered the he knew a lot of other people were supplement that is safe and has potential for the most going through the same thing,” says minimal side effects.” comprehensive program – where Jyu-Yuan Chen. “We recognized basic researchers and clinicians that UCLA was an excellent could work together to translate place for a center where ideas laboratory findings into better could be exchanged and treatments, drawing on the vast everyone’s input could be resources and expertise within the brought together toward solving Department of Neurology and this disease. It has been very across the UCLA campus. “My father was impressed with UCLA’s gratifying to see that begin to emphasis on speeding up the occur.” process of applying the latest Partners in Discovery research findings to patient care,” Frank Chen says. Researchers at the Chen Center are fighting Parkinson’s disease on Christopher DeGiorgio, M.D., many fronts, from exploring Professor-in-Residence of Neurology surgical solutions and Executive Vice Chair of Clinical environmental causes to Affairs 5
  • 6. Introducing Allan D. Wu, M.D. 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 Dr. Wu applying TMS to a regions during the planning or execution volunteer in a study of visual of routine arm movements. In perception conjunction with fMRI, TMS is used to develop maps of the brain that show how movement disorders can affect the llan Wu, M.D., joined the brain and cause movement problems in UCLA Department of patients. Neurology in the Division of TMS has been available at UCLA Movement Disorders last August, since the founding of the Brain Mapping bringing to UCLA his clinical expertise Center, but mostly as a brain-mapping in Parkinson’s disease, dystonia, tremor tool in neurologically normal subjects. and botulinum toxin injections. Dr. Wu As associate director of the center’s is also interested in using research TMS Laboratory, Dr. Wu joins the methods such as 3-D movement director, Dr. Marco Iacoboni, in further analysis, transcranial magnetic developing TMS resources at UCLA. stimulation (TMS) and functional MRI Dr. Wu hopes to expand TMS research (fMRI) to better understand the at UCLA to patients with movement problems that affect patients with disorders and to eventually explore the movement disorders. potential of therapeutic uses of TMS. Dr. Wu has a B.S. in electrical Already, planning is underway for bioengineering from UC Berkeley, projects that will study TMS as a Analysis of TMS induced received his M.D. degree from Johns potential treatment for some of the muscle twitches Hopkins School of Medicine and symptoms in Parkinson’s disease or completed neurology residency at the dystonia. Harvard Longwood Neurology Training “I am driven by the question of Program in Boston. Following how the nervous system controls residency, he completed two movement,” Dr. Wu explains. “ComingPartners in Discovery fellowships: first, in neuromuscular to UCLA and this department has given disease electromyography at the Lahey me a tremendous opportunity to pursue Clinic in Burlington, Mass.; and second, this question, to better understand what in movement disorders at USC. Dr. Wu occurs within the brain of patients who remained at USC as a member of the have movement disorders and to help Example of using TMS to study clinical faculty for four years before design therapies to improve patients’ reaction time (RT) coming to UCLA. symptoms.” Dr. Wu’s research interests focus on how the brain controls the arm and Allan D. Wu, M.D. 6
  • 7. Kudos Donor Recognition Andrew Charles, M.D., has been named by The American DirecTV raised $255,000 Headache Society as the recipient of the 2006 Seymour for the UCLA Multiple Solomon Presidential Lecture award. This prestigious award Sclerosis Program at the is highlighted by a lecture that provides an update on Dr. ninth annual DirecTV Charles’ work on cortical spreading depression and how it will lead to a better understanding of the physiological Charity Golf Classic held underpinnings of the migraine aura and influence progression at the Rio Secco Golf in this area of scientific inquiry. Course in Las Vegas January 4. John Suranyi, Daniel Geschwind, M.D., Ph.D., has been appointed to the president of sales and Gordon and Virginia MacDonald Endowed Chair in Human service for DirecTV, Genetics. This endowed chair is intended for a scientist whose presented the check to Dr. research focuses on neurogenetics. Dr. Geschwind’s focus within neurogenetics includes both neurodevelopmental and John Mazziotta, chair of the neurodegenerative areas. UCLA Department of Neurology, and Dr. Rhonda John C. Mazziotta, M.D., Ph.D., was featured in the October Voskuhl, director of the 24, 2005 issue of Time. Dr. Mazziottas project, the International UCLA MS Program. This Consortium for Brain Mapping, is a 12-year collaborative event has grown effort to create an atlas of the human brain. Coordinated by increasingly successful Drs. Mazziotta and Arthur Toga, this project will result in an atlas to be released online in 2007 and stored at UCLA using since its inception, raising data storage robots with 1 petabyte of data capacity, which more than $1 million to is equivalent to a book with 250 billion pages. The atlas will benefit doctors, assist the UCLA MS who will soon be able to compare a patients brain to that of 7,000 normal Program in its efforts to brains to locate a problem area. develop new therapies and provide excellent care for Jeffrey Saver, M.D., published in Stroke: Journal of the patients with MS. 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 Partners in Discovery 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. 7
  • 8. Neurology Programs and Program DirectorsAlzheimers Disease Health Services NeurogeneticsJeffrey Cummings, M.D. Barbara Vickrey, M.D., M.P.H. Daniel Geschwind, M.D., Ph.D.Brain Mapping LONI Neuromuscular DiseasesSpring 2006John Mazziotta M.D., Ph.D. Arthur Toga, Ph.D. Michael Graves, M.D.Brain Tumor Movement Disorders Neuro-otologyTimothy Cloughesy, M.D. Jeff Bronstein, M.D., Ph.D. Robert Baloh, M.D.Education Multiple Sclerosis Neuro-rehabilitationPerrin Pleninger, M.D. Rhonda Voskuhl, M.D. Bruce Dobkin, M.D.Epilepsy Neuro-AIDS SleepJerome Engel, M.D., Ph.D. Elyse Singer, M.D. Frisca Yan-Go, M.D.   Headache Neurodegeneration StrokeAndrew Charles, M.D. Marie-Francoise Chesselet, M.D., Ph.D. Jeffrey Saver, M.D. HealthcareDepartment of NeurologyAttention: Garnet JohnsonReed Neurological Research Center710 Westwood Plaza NON-PROFITLos Angeles, CA 90095 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