ucla neurology newsletter, spring 2006 - neurology

8

Click here to load reader

Upload: marina761

Post on 25-Jun-2015

259 views

Category:

Health & Medicine


3 download

TRANSCRIPT

Page 1: UCLA Neurology Newsletter, Spring 2006 - NEUROLOGY

Headache Program Bringing Reliefto Widespread, Poorly Understood Problem

vol.2, no.1

NEUROLOGY

UCLA Neurology Newsletter

ew medical disorders are ascommon, or cause as muchdisability, as headache. Hundreds

of millions of individuals worldwide– including an estimated one in fourwomen and one in 10 men – sufferfrom migraines. And yet, despite thestaggering social and economic societalcosts of migraine (hundreds of millionsof days of disability and tens of billionsof dollars in employer costs per year),it remains poorly understood.Consequently, many patients are unableto control their headaches with currenttreatments.

“Headache has beenunderappreciated as a basic scienceand clinical problem,” says AndrewCharles, M.D., professor in UCLA’sDepartment of Neurology. “When youconsider its prevalence and the amountof suffering and disability it causes,funding for headache research has beentrivial compared with funding to studyother medical disorders.”

Only a handful of programs in thecountry combine multidisciplinaryresearch, training, and therapy inheadache. One of those is the UCLAHeadache Research and TreatmentProgram, under the direction of Dr.Charles. The program is dedicated toincreasing the understanding of themolecular and cellular basis ofheadaches – including genetic,hormonal, and chemical influences –and applying that knowledge tooptimizing treatment. Physicians andscientists are trained to have a bettergrasp of the basic and clinical aspectsof headache, and new therapeuticapproaches are being studied at the

same time that a multidisciplinary teamtreats headache patients with bothpharmaceutical and non-pharmaceutical strategies.

The research effort is proceedingon several fronts. Genetics is believedto play an important role in some ofthe most common forms of headache,including migraines, but for the mostcommon types of migraine, theresponsible genes have not yet beenidentified. Investigators in the UCLAHeadache Research and TreatmentProgram are homing in on the genessuspected to be involved, and studyingthe functional consequences of geneticchanges that might be related toheadache disorders. Researchers are

also seeking a better understanding ofthe basic physiological mechanisms ofheadaches. Migraines are associatedwith a variety of significant changesin the electrical activity of the brain,which can be documented withsophisticated electrophysiologicalrecording techniques. The program’sresearchers have developed a high-resolution technique that visualizes aprocess believed to underlie migrainesin mice. “In the living mouse, we cannow visualize a spreading wave ofbrain activation that we think is afundamental basis for migraines,” Dr.Charles says. “We can use this modelto investigate genes and hormones thatmay influence migraine, and to identifytherapeutic approaches to block themigraine before it starts or treat it onceit begins.” A study on the role of femalehormones in headache is yieldinginteresting results, Dr. Charles notes.Other studies are investigating thepharmacology of headache, in an effortto identify drug treatments.

Human functional imagingtechniques are yielding exciting newfindings, Dr. Charles says, by providinga window into which scientists canview the dramatic, dynamic changesin the brain activity of headachepatients with unprecedented resolution.UCLA’s internationally leadingfunctional imaging program is also aboon to the Headache Program’s effortsto develop experimental models tostudy migraines.

“There are a variety of fairly simplechanges people can make to helpreduce the frequency and severity ofheadaches,” says Dr. Charles. “We

Andrew Charles, M.D.Headache Program Director

Page 2: UCLA Neurology Newsletter, Spring 2006 - NEUROLOGY

2

Part

ners

in D

isco

very

Production Manager: Garnet Johnson

Writer/Editor: Dan Gordon

Designer: [Maggie] Huyentrang T. Nguyen

Photographer: Reed Hutchinson

InsidethisIssue... 5 Family Establishes Center to

Find Answers for Parkinson's

6 IntroducingAllan D. Wu, M.D.

7

4

Donor RecognitionKudos

Epilepsy Alternatives

Headache Program Bringing Reliefto Widespread, Poorly Understood Problem [continued]

help patients identify potential triggersand work to avoid those triggers.” Acentral theme for the headache patientshould be consistency, he explains.Irregular sleep and exercise, skippedmeals, unbalanced diets and fluctuatingcaffeine levels can all trigger headaches;patients are advised to keep theselifestyle elements as constant aspossible. Neurologists in the programalso help patients find the rightmedication or combination ofmedications to best treat their specifictype of headache. The program has alsobegun to establish clinical trials to testnew therapies for headache patientswho have failed to find relief fromexisting treatments. Some of these newtherapies have been identified by studiesdone in Dr. Charles’s laboratory.

In addition to providing high-quality patient care, the UCLAHeadache Research and Treatment

Program aims to educate thebroader community ofphysicians in both basicand specialized headachetreatment. A fellowshipprogram is training futureheadache specialists, andseveral outreachprograms are educatingcommunity physiciansin current headachediagnosis andmanagement.Headaches are oftenimproperly diagnosedand treated, even in themedical community,Dr. Charles notes. Forexample, many patientsare misdiagnosed ashaving sinus headacheswhen they actually aresuffering from migraines;as a result, the medicationsprescribed to treat them areless than optimal. “Thetreatment of headache in thecommunity varies greatly,”says Dr. Charles. “We’re tryingto formalize the understanding ofheadache so that there’s a higherstandard of care.”

As more is learned about migraines,experts are beginning to suspect thatthey may be a fundamental property ofthe human nervous system, with geneticand environmental factors affecting thethreshold beyond which individualswill experience them. “That means notonly that migraine is an extremelycommon disorder with a huge impacton quality of life and disability

worldwide,” saysDr. Charles, “but also thata better understanding ofmigraine may lead to a betterunderstanding of the basic function ofthe brain. This understanding mayprovide insight into other neurologicaldisorders, from stroke and epilepsy tobrain cancer and brain trauma.”

Page 3: UCLA Neurology Newsletter, Spring 2006 - NEUROLOGY

3

Part

ners

in D

isco

very

Letter from the Chair

his year marks the 50thAnniversary of the UCLADepartment of Neurology.

While we in the department are proudof all that has been accomplished inthese last five decades, we have chosento celebrate this anniversary not bylooking back, but rather by lookingforward. We have committed an entireyear of activities to just this purpose

and have named the events of the year50 and Forward. The most importantaspect of this anniversary year will bea campaign with you, our Partners inDiscovery, to continue to build ourrelationship with individuals in thecommunity and the private sector toraise public awareness and unrestrictedfunds that will help support research,education and patient care for ourmission – namely, the quest to help

understand diseases of the nervoussystem and treat patients withneurological disorders.

Events will take place throughoutthe year, and an important aspect ofthese activities will be to grow theranks of the Partners in Discovery.Everyone has something to contribute.For some it is their time, for others itis funding and, for all of us, our

expertise. Togetherwe will make this yeara landmark and aturning point. It islikely that in the nextthree to four years, wewill learn more aboutthe normal functionsof the nervous systemand disorders thataffect it than we havelearned in the last 50.Advancedtechnologies and newinsights into thefunction of the brain,spinal cord and nervesare accelerating at anunprecedented rate.We are at the point ofconverting promisesof progress todeliverable treatmentsfor our patients.

Originally adivision of theDepartment ofMedicine at UCLA,

Neurology became a departmentthrough the foresight and strongleadership of its first chairman,Augustus S. Rose, M.D. Dr. Rose, withfive other faculty, launched an effortto create a department that would servepatients with neurological disordersand provide research leading to bettertreatments and, ultimately, cures forthese disorders. The department hasgrown over the years under the able

leadership of two subsequent formerchairs, Richard Walter, M.D., andRobert Collins, M.D., to the pointwhere we now have more than 100faculty and nearly 200 trainees.

For the last three years, thedepartment has consistently beennumber one or number two in researchfunding from the National Institutesof Health. This is perhaps the mostrigorous metric of the quality andquantity of scientific research that wehave in the United States. 50 andForward will be a critical aspect ofaccelerating this process at UCLA and,with your commitment and loyalparticipation, seeing the fruits of 50years of effort delivered directly topatients with neurological disorders –not just here at UCLA, but throughoutthe world.

Dear Friends,

John Mazziotta, M.D., Ph.D.Chair, Department of NeurologyStark Professor of Neurology

Page 4: UCLA Neurology Newsletter, Spring 2006 - NEUROLOGY

4

Part

ners

in D

isco

very

Promising Alternatives Emerging forEpilepsy Patients Not Helped by Drugs

orty percent of the 2.5 millionpeople in the United Stateswith epilepsy have poorlycontrolled seizures. Recurrent

seizures lead to social isolation,unemployment, inability to drive, andinjuries from falls and burns, as wellas drowning. Despite the introductionof multiple new antiepileptic drugssince the 1990s, as many as one millionindividuals with epilepsy across thecountry fail to benefit from drugtreatment. While surgery can beeffective, many patients are either notideal candidates or lack access to oneof the few specialized epilepsy centers,such as UCLA, where surgery isoffered.

“Most people with chronicepilepsy who have continuing seizuresare drug-resistant,” says ChristopherDeGiorgio, M.D., Professor-in-Residence of Neurology at UCLA.“Even with the new drugs, at least halfof these individuals are not beinghelped, and only 5-10 percent of thosewho take the newer drugs becomeseizure-free. In addition, anti-seizuredrugs can have significant side effectson behavior, thinking, and alertness.Women taking anti-seizure drugs andtheir unborn children are at special riskbecause of the effect of these drugs onfetal growth and development. For allof these reasons, we need to find non-drug alternative treatments.”

The first is a new non-drug therapydeveloped for use in humans by Dr.DeGiorgio and Dr. Alan Shewmon, incollaboration with Dr. Todd Whitehurstfrom Advanced Bionics, Inc., calledtrigeminal nerve stimulation (TNS).TNS uses an implantable “brain

pacemaker” to stimulate a nerve in theface and forehead that extends into thebrain, in an effort to interrupt theprocess of seizure activity. TNS hastwo potential advantages over thecommercially available vagus nervestimulator (VNS), Dr. DeGiorgio notes.“The vagus nerve stimulator isexpensive, and we can’t predict whowill respond to it until after it issurgically implanted,” he explains.“With TNS, we can first test anindividual’s response using aninexpensive neurostimulator thatpatients wear on their belt andelectrodes taped to their face. If itproves beneficial, then it could besurgically implanted under the skin.”In addition, while VNS stimulates onlyone side of the brain, TNS stimulatesboth sides, he notes.

Theconcept,originallytested inanimalstudies byresearchersat DukeUniversity,wasdevelopedand usedfor the firsttime inhumans by

Dr. DeGiorgio’s group in arecently completed pilotstudy. Of the seven peoplewho completed at least three

months wearing the external stimulator,four experienced a 50 percent or betterreduction in seizure frequency; aftersix months, five had such a reduction.Dr. DeGiorgio is currently enrollingpatients in a follow-up study that willseek to extend the findings to 25

patients. A third study will examinethe impact of implanting TNS with anelectrode under the skin (just beneaththe eyebrow) of patients who respondto the external stimulator.

Equally intriguing is a new studybeing launched by Dr. DeGiorgio’sgroup to examine the potential foromega-3 fatty acids, the maincomponent of fish oil, to lower epilepsypatients’ risk of sudden death andreduce seizure frequency and severity.The risk of sudden death for peoplewith epilepsy is 24 times higher thanthat of the general population. Previousresearch by Dr. Thomas Henry, aformer fellow of the UCLA EpilepsyProgram, has found that people withepilepsy have low levels of omega-3fatty acids. Studies have also foundthat omega-3s have many health

benefits –includingreducing therisk of suddendeath in heartdiseasepatients. Inaddition,animal studieshave foundthat omega-3fatty acids,which blocksodiumchannels inboth the heartand the brain,not onlystabilize heart

rhythms, but can also reduce seizureactivity.

Given the strength of the animaldata, Dr. DeGiorgio is starting a pilotstudy for people with poorly controlledepilepsy to determine whether omega-3 fatty acids reduce the risk of suddendeath and their seizure severity andfrequency. “Even if we only find areduced risk of sudden death, thatwould be a major breakthrough,” says

Dr. DeGiorgio and hiscolleagues are currentlypursuing two such alternatives,both of which appear promising.

Page 5: UCLA Neurology Newsletter, Spring 2006 - NEUROLOGY

Epilepsy [continued] Chen FamilyEstablishes Center to Find Answers for Parkinson's

5

Part

ners

in D

isco

very

hen Fu-Hsing Chen wasdiagnosed withParkinson’s disease, his

priorities changed. Thesuccessful entrepreneur, alongwith his wife, Jyu-Yuan,vowed to do something thatwould help others who werealso struggling with thedebilitating disorder. In June2004, they donated funds toestablish the Fu-Hsing and Jyu-Yuan Chen Center forTranslational Research inParkinson’s Disease, based inthe UCLA Department ofNeurology, and to recruit twoof the top clinician researchersin the field.

“The Parkinson’sdiagnosis really came out ofthe blue, and my father decidedto shift his focus from businessto trying to help this cause,”says Frank Chen, son of Fu-Hsing and Jyu-Yuan who,along with his brother, is aUCLA alumnus. He notes that thefamily considered many institutionsthroughout the country beforedeciding that UCLA offered thepotential for the mostcomprehensive program – wherebasic researchers and clinicianscould work together to translatelaboratory findings into bettertreatments, drawing on the vastresources and expertise within theDepartment of Neurology andacross the UCLA campus. “Myfather was impressed with UCLA’semphasis on speeding up theprocess of applying the latestresearch findings to patient care,”Frank Chen says.

Researchers at the Chen Centerare fighting Parkinson’s disease onmany fronts, from exploringsurgical solutions andenvironmental causes to

investigating the potential for usinghealthy stem cells to replacedamaged cells.

“My husband was suffering, andhe knew a lot of other people weregoing through the same thing,” saysJyu-Yuan Chen. “We recognizedthat UCLA was an excellentplace for a center where ideascould be exchanged andeveryone’s input could bebrought together toward solvingthis disease. It has been verygratifying to see that begin tooccur.”

Dr. DeGiorgio. “But we also knowthat the low levels of omega-3 amongpeople with epilepsy can have manynegative health effects. And we havepreliminary data that increasing theiromega-3 levels improves thinkingprocesses and memory, and mayreduce seizure severity. If thishypothesis is borne out in furtherresearch, omega-3s could be to peoplewith epilepsy what folic acid has beenfor pregnant women – a low-costsupplement that is safe and hasminimal side effects.”

Christopher DeGiorgio, M.D.,Professor-in-Residence of NeurologyExecutive Vice Chair of ClinicalAffairs

Fu-Hsing and Jyu-Yuan Chen

Page 6: UCLA Neurology Newsletter, Spring 2006 - NEUROLOGY

6

Part

ners

in D

isco

very

Introducing Allan D. Wu, M.D.

llan Wu, M.D., joined theUCLA Department ofNeurology in the Division of

Movement Disorders last August,bringing to UCLA his clinical expertisein Parkinson’s disease, dystonia, tremorand botulinum toxin injections. Dr. Wuis also interested in using researchmethods such as 3-D movementanalysis, transcranial magneticstimulation (TMS) and functional MRI(fMRI) to better understand theproblems that affect patients withmovement disorders.

Dr. Wu has a B.S. in electricalbioengineering from UC Berkeley,received his M.D. degree from JohnsHopkins School of Medicine andcompleted neurology residency at theHarvard Longwood Neurology TrainingProgram in Boston. Followingresidency, he completed twofellowships: first, in neuromusculardisease electromyography at the LaheyClinic in Burlington, Mass.; and second,in movement disorders at USC. Dr. Wuremained at USC as a member of theclinical faculty for four years beforecoming to UCLA.

Dr. Wu’s research interests focuson how the brain controls the arm and

hand in making movements to point at,reach toward, or hold everyday objects.Understanding how this control isimpaired in patients with movementdisorders such as Parkinson’s diseaseand dystonia can provide insights intohow rehabilitation treatments can helpmovement symptoms in these patients. One of Dr Wu’s researchtechniques is TMS, a safe, noninvasiveand relatively painless method ofstimulating the brain in volunteers withan insulated electromagnetic coil. Thisbrain-mapping method is used toexamine the role of various brainregions during the planning or executionof routine arm movements. Inconjunction with fMRI, TMS is usedto develop maps of the brain that showhow movement disorders can affect thebrain and cause movement problems inpatients.

TMS has been available at UCLAsince the founding of the Brain MappingCenter, but mostly as a brain-mappingtool in neurologically normal subjects.As associate director of the center’sTMS Laboratory, Dr. Wu joins thedirector, Dr. Marco Iacoboni, in furtherdeveloping TMS resources at UCLA.Dr. Wu hopes to expand TMS researchat UCLA to patients with movementdisorders and to eventually explore thepotential of therapeutic uses of TMS.Already, planning is underway forprojects that will study TMS as apotential treatment for some of thesymptoms in Parkinson’s disease ordystonia.

“I am driven by the question ofhow the nervous system controlsmovement,” Dr. Wu explains. “Comingto UCLA and this department has givenme a tremendous opportunity to pursuethis question, to better understand whatoccurs within the brain of patients whohave movement disorders and to helpdesign therapies to improve patients’symptoms.”

Allan D. Wu, M.D.

Dr. Wu applying TMS to avolunteer in a study of visualperception

Analysis of TMS inducedmuscle twitches

Example of using TMS to studyreaction time (RT)

Page 7: UCLA Neurology Newsletter, Spring 2006 - NEUROLOGY

7

Part

ners

in D

isco

very

Kudos

Andrew Charles, M.D., has been named by The AmericanHeadache Society as the recipient of the 2006 SeymourSolomon Presidential Lecture award. This prestigious awardis highlighted by a lecture that provides an update on Dr.Charles’ work on cortical spreading depression and how itwill lead to a better understanding of the physiologicalunderpinnings of the migraine aura and influence progression

in this area of scientific inquiry.

Daniel Geschwind, M.D., Ph.D., has been appointed to theGordon and Virginia MacDonald Endowed Chair in HumanGenetics. This endowed chair is intended for a scientist whoseresearch focuses on neurogenetics. Dr. Geschwind’s focuswithin neurogenetics includes both neurodevelopmental andneurodegenerative areas.

John C. Mazziotta, M.D., Ph.D., was featured in the October24, 2005 issue of Time. Dr. Mazziotta's project, the InternationalConsortium for Brain Mapping, is a 12-year collaborativeeffort to create an atlas of the human brain. Coordinated byDrs. Mazziotta and Arthur Toga, this project will result in anatlas to be released online in 2007 and stored at UCLA usingdata 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 normalbrains to locate a problem area.

Jeffrey Saver, M.D., published in Stroke: Journal of theAmerican Heart Association his research synthesizing newbrain-imaging and cell-counting techniques to quantify nervecell loss in stroke. He found that a stroke victim loses 1.9million neurons every minute in which treatment is notdelivered. The calculations were for the most common typeof stroke, an ischemic stroke, caused when a blood clot blocksblood flow to the brain.

Rhonda Voskuhl, M.D., director of the UCLA MultipleSclerosis Program, and her colleagues were awarded theCollaborative Multiple Sclerosis Research Center Award bythe National Multiple Sclerosis Society. This $825,000 awardis given over the next five years and is one of only three awardsgiven 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 $255,000for the UCLA MultipleSclerosis Program at theninth annual DirecTVCharity Golf Classic heldat the Rio Secco GolfCourse in Las VegasJanuary 4. John Suranyi,president of sales andservice for DirecTV,presented the check to Dr.John Mazziotta, chair of theUCLA Department ofNeurology, and Dr. RhondaVoskuhl, director of theUCLA MS Program. Thisevent has grownincreasingly successfulsince its inception, raisingmore than $1 million toassist the UCLA MSProgram in its efforts todevelop new therapies andprovide excellent care forpatients with MS.

DonorRecognition

Page 8: UCLA Neurology Newsletter, Spring 2006 - NEUROLOGY

Neurology Programs and Program Directors

NON-PROFIT

ORGANIZATION

U.S POSTAGE

PAID

UCLA

United in PurposePartners in Discovery

To join Partners in Discovery contact: Garnet Johnson [310] 206 5769 or [email protected]

HealthcareDepartment of NeurologyAttention: Garnet JohnsonReed Neurological Research Center710 Westwood PlazaLos Angeles, CA 90095

Spring 2006Neurogenetics 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-AIDSElyse Singer, M.D.  Neurodegeneration Marie-Francoise Chesselet, M.D., Ph.D.

Alzheimer's DiseaseJeffrey 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.