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Pandemic influenza A(H1N1)virus should be considered

in the differential diagnosis forchildren who present with in-fluenzalike illness accompaniedby unexplained seizures or men-tal status changes.

That recommendation wasmade by the U.S. Centers for

Disease Control and Preven-tion (CDC) in a report of fourchildren with neurologicalcomplications associated withH1N1 influenza virus infectionseen in Dallas County, Texas,U.S.A., during May 2009. Allfour children, who were aged 7-17 years, were admitted withsigns of influenzalike illness(ILI) and seizures and/or al-tered mental status. Three of

the four patients had abnormalfindings on electroencephalog-raphy. In all four patients,H1N1 influenza viral RNA wasdetected in nasopharyngealspecimens but not in cere-brospinal fluid, the CDC said(MMWR 2009;58:773-8).

The four children wereamong a total of 405 personswith confirmed pandemic fluseen at all hospitals in Dallas

County since April 22, including44 who were hospitalized.There were no deaths reported.Of all the confirmed cases, 83%were in patients who wereyounger than 18 years of age.Of seven possible cases of neu-rological complications, threewere excluded either becausethey were found to have alter-native etiologies or because theydid not meet the case definition.

Two of the children—a 17-year-old black male and a 10-year-old Hispanic male—hadbeen previously healthy. Theolder child was admitted witha fever, cough, headache, dizzi-ness, and weakness and laterdeveloped disorientation andconfusion. The younger childhad had a 3-minute tonic-clonic

B Y D O N N A C. B E R G E N, M . D.

Chair, Public Relations and WHO Liaison Committee, WFN

Collaboration between the World Federation of Neurologyand the World Health Organization has moved into the im-portant area of disease classification.

Although systems of disease classification were begun as early asthe 18th century, since its founding in 1946 the WHO has been re-sponsible for preparing and updating the International Lists of Dis-eases and Causes of Death (ICD). In fact, the ICD is more than 100years old, making it older than the WHO. One of the WHO’s ear-liest official actions was to approve the ICD-6.

Since then, the WHO has periodically revised the ICD codes. Thecurrent ICD-10, which is being used in most countries, was ap-proved in 1990 by the World Health Assembly, which consisted ofthe health ministers of the WHO member states. The codes areused as universally recognized diagnostic labels by clinicians, by epi-demiologists charting disease prevalence and incidence, by re-searchers, and by public health officials and health care plannersresponsible for resource allocation and training programs. Min-istries of health use the code when reporting causes of death anddisease rates to the WHO, and some health systems use the dis-ease codes in reimbursement for health care. (Some countries, no-tably the United States, still use the ICD-9 version.)

In June, the ICD-11 Committee was convened in Geneva by Dr.Shekhar Saxena and Dr. Tarun Dua of the WHO’s Programme forNeurological Diseases and Neuroscience, Department of MentalHealth and Substance Abuse, the WHO division that is responsiblefor disorders of the nervous system. The meeting was chaired byDr. Raad Shakir of Imperial College, London. Representativesfrom a range of international neurological organizations partici-pated, including Alzheimer’s Disease International, the International

Brain Research Organization, International Child Neurology As-sociation, World Federation of Neurosurgical Societies, Interna-tional Neuropsychological Society, International League AgainstEpilepsy, International Headache Society, Multiple Sclerosis Inter-national Federation, World Stroke Organization, and MovementDisorder Society. Dr. Johan Aarli represented the WFN. The revi-sion will include three versions: for primary health care workers,

NeurologyWorld

VOL. 24 • NO. 5 • OCTOBER 2009

Neurological Complications Seen in 4 Children With H1N1

WFN, WHO Take on ICD-10 RevisionsT H E O F F I C I A L N E W S L E T T E R O F T H E W O R L D F E D E R A T I O N O F N E U R O L O G Y

See H1N1 • page 15

I N S I D E

See ICD-10 • page 14

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WCN 2009Named Orations honorEddie and PilooBharucha, B.S. Singhal,Melvin D. Yahr, andRichard L. and MaryMasland, for their life-long contributions to thefield of neurology. PA G E 5

Krasnoyarsk KraiThe capital city of thisremote Siberian region isa hub of research, clinicalpractice, and training forneurologists. PA G E 8

Going GlobalThe Multiple SclerosisInternational Foundationand the World StrokeOrganization hone plansfor raising worldwideawareness of the diseasesand promoting researchand clinical collaboration. PA G E 1 2

The WFN’s Dr. Donna Bergen and Dr. Johan Aarli (front, 3rd and5th from left) with representatives from international neurologicalorganizations at a meeting of the WHO’s ICD-11 committee inGeneva. Dr. Raad Shakir (front, 3rd from right) was the chair. Themeeting was convened by Dr. Shekhar Saxena (front, 5th fromright) and Dr. Tarun Dua (front, 4th from left) of the WHO.

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2 • WORLD NEUROLOGY WWW.WFNEUROLOGY.ORG • OCTOBER 2009

WORLD FEDERATION OF NEUROLOGYEditor in Chief Dr. Mark Hallett (U.S.A.)

EDITORIAL ADVISORY BOARDDr. Pierre Bill (South Africa); Dr. William M. Carroll (Australia); Dr. Jagjit S. Chopra (India); Dr. Michael Finkel (U.S.A.); Dr. Osvaldo Fustinoni (Argentina); Dr. Francesc Graus (Spain);Dr. Alla Guekht (Russia); Dr. Theodore Munsat (U.S.A.); Dr. Daniel Truong (U.S.A.); Dr. Alexandros Tselis (U.S.A.)

WFN OFFICERSPresident: Dr. Johan A. Aarli (Norway)First Vice-President: Dr. Vladimir Hachinski (Canada)Secretary-Treasurer General: Dr. Raad Shakir (United Kingdom)

ELECTED TRUSTEESDr. Gustavo Romano (U.S.A.); Prof. Werner Hacke (Germany); Dr. Ryuji Kaji (Japan)

CO-OPTED TRUSTEESDr. Roger Rosenberg (U.S.A.); Dr. Niphon Poungvarin (Thailand)

REGIONAL DIRECTORSDr. Alfred K. Njamnshi (Pan Africa); Dr. Jacques De Reuck(Europe); Prof. Riadh Gouider (Pan Arab); Dr. Amado San Luis(Asian-Oceania); Dr. Robert Griggs (North America); Dr. AnaMercedes Robles de Hernandez (Latin America)

EXECUTIVE DIRECTORKeith NewtonWorld Federation of NeurologyHill House, Heron SquareRichmond, Surrey, TW9 1EP, UKTel: +44 (0) 208 439 9556/9557 Fax: +44 (0) 208 439 [email protected]

EDITOR OF THE JOURNAL OF THE NEUROLOGICAL SCIENCESDr. Robert Lisak (U.S.A.)

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©Copyright 2009, by the World Federation of Neurology

EDITOR IN CHIEF’S COLUMN

Neurologists at the MoviesNeurologists are people, too, and

often go (or should go) to themovies for entertainment and fun.

Sometimes the movies have medical oreven neurological themes. In these cir-cumstances, we might well have a spe-cial interest. How are the patients thatwe see portrayed on the big screen? Inaddition, of course, ourfriends, colleagues, and evenour patients may well wantto know what we do thinkabout a particular movie.Lay groups are often excitedabout movies that illustratetheir disease; the moviemakes their problem betterknown and increases sym-pathy for the symptomsthey have.

What’s the advantage of amovie review? The reviewlets us know about the film, to help usmake a decision as to whether we wantto go. If we don’t go, then we are at leastsomewhat knowledgeable about thefilm. In addition, we can get an expert’sviewpoint on the film. That sort of edu-cation can certainly increase our under-standing of the disorder that is being por-trayed, point out subtleties that we mightmiss, and increase our enjoyment over-all. On page 19 of this issue of WorldNeurology, we have two movie reviewsby experts: John Halperin reviews amovie on chronic Lyme disease, andDon Gilbert reviews a movie on Tourettesyndrome.

The movie on chronic Lyme disease,“Under Our Skin,” is a documentary by

advocates of the idea that many chron-ic, often vague, neurological symptomsmay be due to a chronic Lyme infection.No use that the American Academy ofNeurology and the Infectious Disease So-ciety of America, upon careful and de-tailed review of all the evidence, haveconcluded that Lyme disease is general-

ly not responsible for thesymptoms complainedabout. Physicians are por-trayed as nonsympatheticand the scientific method asmisguided. This is an im-portant area to know about.Many patients feel verystrongly that their symp-toms are due to chronicLyme disease, and thismovie will strengthen theirbelief. Proper treatment ofthe patient will require tak-

ing this belief into account. Often som-atization is the underlying disorder.

The movie on Tourette syndrome,“Phoebe in Wonderland,” is an enjoyablestory, but the lead character seems tohave mainly obsessive compulsive disor-der and impulsive behaviors. In fact, al-though the diagnosis of Tourette syn-drome is made, the patient does nothave any tics! Again, the movie makerhas the wrong diagnosis, and the movie-goers may well be misled. So for bothmovies, the neurologist has an opportu-nity, and, perhaps even a responsibility, tocorrect any misconceptions these moviesmight create.

We watch so you don’t have to—butyou may well want to, anyway. ■

BY MARK HALLETT, M.D.

WCN 2009

First Advocacy Session IsPlanned for Bangkok

The World Federation of Neurologywill offer the first session of its kind

on advocacy training on Oct. 29 at the2009 World Congress inBangkok.

Course faculty will in-clude the president of theWorld Neurology Founda-tion, Dr. Michael Finkel,Dr. Mohammad Wasay, Dr.Man Mohan Mehndiratta,Dr. Wolfgang Grisold,American Academy ofNeurology staff, and inter-national graduates of theAAN’s Palatucci AdvocacyLeadership Forum.

They will present a structured pro-gram that will teach attendees howbest to advocate for their patients and

our specialty based on the conditionsin their home countries and how topresent one’s original project to rep-

resentatives of media andgovernment.

The course is a Scientif-ic Session and does not re-quire preregistration or ad-ditional charges.

It will be very useful toindividuals as well as na-tional societies that wishto follow the example ofthe Indian Academy ofNeurology and establish asection on advocacy.

Questions regarding the session canbe directed to Dr. Finkel at [email protected] or Melissa Larsonat [email protected]. ■

Council of Delegates Meeting:Register if You Want to Vote

The 2009 Council of Delegates willbe held in Bangkok during the

World Congress of Neurology on Oct.25 from 10:00 a.m to noon, followed bya lunch from noon to 1:00 p.m.

If necessary, the Council will recon-vene for a second session on Oct. 29from 2:00 p.m. to 4:00 p.m.

All delegates are required to com-plete a delegate attendance form and

return it to the WFN head office assoon as possible. If you have not yet re-ceived such a form, please contact thehead office at [email protected].

Please also note that if you fail to reg-ister your society for the Council ofDelegates meeting or to ensure thatyour dues payments are fully up todate, your delegate will be ineligible tocast a vote at this year’s elections. ■

DR. MICHAEL FINKEL, M.D.

01_2_3_6_7_14_15wfn9_9.qxp 9/10/2009 1:57 PM

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PRESIDENT’S COLUMN

Bangkok 2009 and Beyond Ihope that this

column reach-es the WFN

membership intime for theWorld Neurolo-gy Congress thatopens on Oct. 25.All of us aredeeply indebted

to the Neurological Society of Thailandfor its hard work in preparing for this im-portant event.

More than any previous WCN host so-ciety, the Thai organizers have had theirshare of unexpected obstacles in theplanning of the congress. Global air trav-el has fallen off as the financial crisis hashit economies around the world. Pas-senger volumes have declined, and meet-ings and international conventions havetaken the hardest hit, though this is nowslowly improving. We have seen somepolitical unrest, but law and order havebeen restored. And as if this was notenough, the WHO declared the influen-za A(H1N1) a pandemic, but considersthe overall severity of the pandemic to bemoderate. This means that most peoplerecover from infection without the needfor hospitalization or medical care. Thereis no reason to assume that the risk ofcontracting influenza is higher in Thai-

land than in the home country. Nevertheless, the Thai neurologists

have managed to prepare for this world’slargest scientific event in neurology in aprofessional, open, and well-balancedway. Most participants have alreadybought their tickets and made hotelreservations for this unique week inBangkok. Hopefully, many guests willalso have the opportunity to explore thisexotic, beautiful, and cultured country.

The congress presents a unique possi-bility for neurologists from all regions ofthe world to receive information and beupdated on developments in the neuro-sciences. The main topic themes arestroke, multiple sclerosis, epilepsy, de-mentia, movement disorders, and pain.There will be plenary lectures, namedlectures, debate sessions, invited lectures,industry-sponsored satellite symposia,free papers, poster sessions, and the 3rdTournament of the Minds.

The WCN 2009 will also be a meetingground for discussions on the relation-ship between neurology and publichealth. I would like to prepare the par-ticipants for debates on the role of WFNin joining WHO’s work on the develop-ment of clinical neurology.

The WHO Mental Health Gap ActionProgramme, starting almost simultane-ously with the Bangkok congress, clearly

signals the need to scale up medical ser-vices for mental, neurological, and sub-stance use disorders. The program is de-signed for low- and lower-middle–incomecountries. By doing this, the WHO hastaken an important step to show its re-sponsibility for the great global burden ofneurological disorders.

The WHO and WFN have clearlydemonstrated that there are inadequateresources for patients with neurologicaldisorders living in low-income or devel-oping regions. Most patients still have noaccess to a neurologist. They may seegeneral practitioners, nurses, or healthcare workers who may have some or notraining in diagnosis and care of com-mon neurological disorders. A lack of re-liable diagnostic and therapeutic toolsadds to the problem.

If there is no neurologist available, it isour mission to see that the available healthworkers also have a basic training in neu-rology. But to do that, we need a com-prehensive system of neurological care atthe primary care level, including trainingof primary health-care workers. We needgeneral practitioners and health workersto find out what neurology is and is not.

Such training in diagnosis and man-agement of common and treatable neu-rological disorders for health providers isessential. We are not talking about in-

frequent disorders. We are talking aboutsome of the most common disorders,such as epilepsy, stroke, migraine, pe-ripheral neuropathies, and Parkinson’sdisease. A general practitioner has to beupdated on these disorders.

Neurology needs a better contact withprimary health care. Rural communityhealth centers may develop into the crit-ical link only if they have contact withneurological centers. This could formthe backbone of a national program forneurology care.

But there are many medical schoolsthat have no neurologist to give medicalstudents even basic training in neurolo-gy. What then about the training of nurs-es and auxiliary health personnel?

To establish adequate neurologicalcare, three sets of critical elements are es-sential: basic public health service andprimary health care, neurology trainingat all medical schools, and a national neu-rology service system. The three are in-terwoven and depend upon each other.Basic public health service and primaryhealth care is essential to develop mod-ern neurology in countries lacking amedical infrastructure. Thailand is agood example of a once developingcountry that has developed into a mod-ern highly developed nation. I look for-ward to meeting you in Bangkok. ■

BY JOHAN A. AARLI, M.D.

B Y B E T S Y B AT E S


Pain and depression are common bedfellows, en-twined in a complex relationship of situational and

neurophysiological connections that are not yet fullyunderstood.

Numerous studies point to frequent comorbidity, yetphysicians treating patients who present with one con-dition often fail to assess for the other.

It is unknown whether depression is the “cause or theconsequence” of chronic pain in some circumstances.This emphasizes the need for a patient with chronicpain to be comprehensively assessed for both condi-tions, said Dr. Charles E. Argoff, professor of neurolo-gy and director of the Comprehensive Pain Programat Albany (N.Y.) Medical College.

But this is challenging to do in the real world because“so much of taking care of people is based on the last1,000 people you have taken care of and what your ex-periences have been in addition to your textbooks andthe mentorship you receive during training.”

Neurologists can manage patients’ depression andanxiety if they feel comfortable doing so or refer theperson for treatment in the community. Depression andanxiety that remain untreated will limit the usefulnessof any pain treatments, Dr. Argoff said in an interview.

That does not necessarily mean, however, that treat-ing a depressed patient with chronic diabetic neuropa-thy will only require prescribing a serotonin-norepi-nephrine reuptake inhibitor such as duloxetine.

“The point is that there are many considerations to bemade, but there is no clear-cut, routine, easy, slam-dunksolution,” Dr. Argoff said. If someone is depressed, hasmigraines, and is obese, “I wouldn’t necessarily put them

on a tricyclic antidepressant because of the side effect ofweight gain, despite it’s efficacy in chronic headache.”

Some medications can have multiple effects that areparticularly useful in treating certain patients, such asthose with diabetic neuropathy who are already takinga selective serotonin reuptake inhibitor (SSRI) agent suchas fluoxetine for depression. In this case, a pain special-ist may want to switch the patients’ SSRI to the sero-tonin-norepinephrine reuptake inhibitor duloxetine,which is U.S. Food and Drug Administration–approvedfor the treatment of painful diabetic neuropathy, de-pression, generalized anxiety disorder, and fibromyalgia.Another option, the anticonvulsant pregabalin, an ago-nist of the alpha 2 delta subunit in voltage-gated calci-um channels, is indicated for diabetic neuropathy andin Europe may be used for generalized anxiety disorder.

Dr. Michael Clark, a psychiatrist who directs the JohnsHopkins Pain Treatment Program in Baltimore, said heis “pretty nonbiased when it comes to drug selectionand pretty pragmatic with regard to a person’s indi-vidual situation.” By the time patients see him, theymay have been prescribed an array of the newer, moreexpensive drug choices, so he may turn to a tricyclic an-tidepressant (such as amitriptyline or doxepin) or an an-tiseizure medication such as divalproex or lamotrigine.

“Often, no one else has tried these medications inthese patients, and I’m comfortable with using them,”Dr. Clark said, explaining that rare side effects, carefultitration, and blood monitoring are not daunting, onceone has familiarity with them.

Dr. Jon Mark Streltzer, professor of psychiatry at theUniversity of Hawaii, Honolulu, maintains that the con-troversy surrounding long-term, high-dose opioid usefor chronic pain is a matter of difference among indi-viduals, rather than a specialty-specific perspective.

However, he generally prefers to manage chronic painpatients (where possible) on acetaminophen (1 g, 4times daily) while using a program aimed at function,activity through functionally directed therapy, includ-ing cognitive-behavioral psychotherapy.

That said, acetaminophen “won’t work on opioid-de-pendent patients,” he warned. “Almost nothing willwork until the dependence is treated.”

Within the larger context of chronic pain, patientswith generalized pain syndromes deserve special con-sideration, Dr. Clark said.

Central sensitization appears to be the common de-nominator among fibromyalgia, interstitial cystitis, dif-fuse low back pain, chronic fatigue syndrome, irritablebowel syndrome, and headache syndromes, with re-sulting amplified pain sensations.

“The most important thing is that you don’t want togive these patients a little bit of everything and thinkthat’s the answer: a little bit of occupational therapy, alittle bit of physical therapy, a little bit of psychother-apy and psychopharmacology. Throwing ingredientsinto a soup without a recipe is not the answer. Thesepatients need to have someone design a rational planfor their care,” Dr. Clark said.

Dr. Streltzer reported no relevant financial conflictswith regard to this story. Dr. Clark has served on thespeakers bureau or as a consultant for Eli Lilly & Co.,maker of duloxetine, and Pfizer Inc., maker of pregabalin.

Dr. Argoff has received grant support from severalcompanies involved in pain therapeutics. He also serveson the speakers bureau and advisory boards and is aconsultant to various companies in the field, includingEli Lilly and Pfizer. ■

Jeff Evans contributed to this article.

Develop Rational Plan for Managing Chronic Pain

04_5_8thru13wfn9_9.qxp 9/10/2009 2:23 PM

OCTOBER 2009 • WWW.WFNEUROLOGY.ORG WORLD NEUROLOGY • 5

Eddie Bharucha (b. 1916) and PilooBharucha (1917-2001)Dr. Eddie Bharucha received medicaldegrees in Mumbai and London. Hetrained at Queen Square and Maida Valein London, at the Neurological Institute

in New York under Dr. Houston Merritt,and in Boston under Dr. Denny Brown.

Dr. Bharucha established the first de-partment of neurology in India in 1946.His contributions covered a spectrum ofneurological disorders, including vita-min deficiencies, tuberculosis, epilepsy,cerebral palsy, and hereditary neu-ropathies. His descriptions of craniover-tebral anomalies and the neurologicalmanifestations of acute hemorrhagicconjunctivitis are seminal. He was a jointeditor of the Handbook of Neurology,president of the Neurological Society ofIndia, and a vice-president of the WorldFederation of Neurology. In 1970, he co-founded the Indian Epilepsy Associationand was its secretary until 1991.

Dr. Piloo Bharucha trained as a pedia-trician and obtained her medical degreesin Mumbai and London. She founded thedepartment of pediatrics at the King Ed-ward VII Memorial Hospital in Mumbai.Her interests were preventive pediatrics,child welfare, and immunization. Po-liomyelitis immunization became hercrusade. She revitalized the Indian Acad-emy of Pediatrics and served as its pres-ident. She and Dr. Eddie Bharucha mar-ried in 1947, and had three sons. She wasa persistent fighter for everything shebelieved in, whether it was the plight ofill children or animals, the welfare of theunderprivileged, or the environment. To-gether with Eddie, she orchestrated an ef-fort to repeal a law that linked epilepsywith insanity and provided grounds fornullifying marriage.

The 2009 Bharucha Oration will be givenby THIRAVAT HEMACHUDHA, M.D.,professor of neurology at the faculty ofmedicine, Chulalongkorn University,Bangkok, Thailand, on Oct. 26 at 9:15a.m. His main research interest is human

rabies. He is a member of the WHO ExpertAdvisory Panel on Rabies and director ofthe WHO Collaborating Center forResearch and Training in Viral Zoonoses.

B.S. Singhal, M.D. (b. 1933)Dr. B.S. Singhal completed his medicaltraining at Grant Medical College and SirJ. J. Group of Hospitals in Mumbai, andtrained in neurology in London.

He has served as president of the Neu-rological Society of India and the IndianEpilepsy Association; established theParkinson’s Disease Foundation of India;is founder fellow of the Indian Academyof Neurology, the Association of Physi-cians of India, and the International Med-ical Science Academy; and is a member ofthe American Academy of Neurology, theAmerican Neurological Association, theFrench Neurological Society, and the As-sociation of British Neurologists. He has

served on theresearch com-mittee of theWorld Federa-tion of Neu-rology, andwas regionaldirector of theAsian-Ocean-ian Chapter ofthe WFN from2005 to 2009.

Dr. Singhalis the chair of neurology at the BombayHospital Institute of Medical Sciences inMumbai. He is widely respected for hisgentle style, positive approach, and in-credible work ethic. He has contributednearly 200 papers to national and inter-national journals and recognized a formof leukodystrophy unique to the Indiansubcontinent. His many awards includethe Priyadarshini Academy NationalAward for Excellence in Medicine, theWockhardt-Harvard Medical Interna-tional Award for Neurology, and the Dr.B.C. Roy Indian National Award. Dr.Singhal is married to Dr. Asha Singhal.

The Singhal Oration was establishedby Dr. Sorab Bhabha to honor Dr. Sing-hal’s lifelong contributions to neurolog-ical education and research, his clinicalexcellence, and his devotion to patientcare. Dr. Bhabha was a neurologist, afriend and colleague of Dr. Singhal, andhelped establish this lecture before hisdeath from ALS in 2006.

The 2009 Singhal Oration will be given bySAMUEL F. BERKOVIC, M.D., on Oct. 28 at8:00 a.m. He is Laureate Professor in thedepartment of medicine at the Universityof Melbourne and director of the Epilepsy

Research Centre at Austin Health inHeidelberg, both in Australia.

Melvin D. Yahr, M.D. (1917-2004)Dr. Melvin D. Yahr was a lifelong NewYorker. He received his undergraduateand medical degrees at New York Uni-versity, a free education at that time. Headmitted to playing the clarinet in a jazzcombo to earn extra money, although heinsisted that he played badly. After threeyears of military service, he joined theneurology department at Columbia-Presbyterian Medical Center. He waschairman of the department of neurol-ogy at Mount Sinai Hospital in NewYork from 1973 to 1992, and continuedhis clinical practice and research until hisdeath in 2004 at the age of 86.

Based on research in the late 1950sshowing that depletions of the chemicalmessenger dopamine could set off Parkin-son’s disease, Dr. Yahr conducted andpublished the first clinical trials of L-dopain the late 1960s. These studies changedthe outlook for people with Parkinson’sdisease. By 1972, barely 3 years after hisstudy was published, about half of the na-tion’s 1.5 million people with Parkinson’sdisease were taking it. Today, L-dopa, de-spite some side effects, is by far the mostcommon treatment for Parkinson’s. Hewas the first scientific director of theParkinson’s Disease Foundation.

In 1948, he married Felice Turtz, a mar-riage that lasted 44 years until her death in1992. They had four daughters. His daugh-ter Carol remembers that, no matter whothe patients were, or how hopeless theirsituation seemed, her father was alwaysengaged, positive, and supportive.

The 2009 Melvin D. Yahr Lecture will bepresented by ROGER N. ROSENBERG,M.D., on Oct. 29 at 8:30 a.m. He is theZale Distinguished Chair and professor ofneurology and director of the U.S. NationalInstitutes of Health’s Alzheimer’s DiseaseCenter at the University of TexasSouthwestern Medical Center at Dallas,U.S.A. He is a past-president of theAmerican Academy of Neurology, a trusteeof the World Federation of Neurology, andeditor in chief of Archives of Neurology.

Richard Lambert Masland, M.D.(1910-2003)Dr. Richard Lambert Masland wasborn in Philadelphia, U.S.A. He attend-ed Haverford College and the Universi-

ty of Pennsylvania Medical School, andserved residencies in neurology and psy-chiatry at Pennsylvania Hospital, inter-spersed by service in the Air Force dur-ing World War II. He then joined thefaculty of the new Bowman GreySchool of Medicine in Winston-Salem,N.C., U.S.A.

From 1959 to 1968 he was the direc-tor of the National Institute of Neu-rological Diseases and Blindness, andwas part of the team that crafted themerit-based peer-review system that isthe foundation of American medicalresearch. He then became chair of thedepartment of neurology at the Col-lege of Physicians and Surgeons of Co-lumbia University in New York; in1973, he became H. Houston MerrittProfessor of Neurology, emeritus.

Dr. Masland mentored many of themost gifted research neurologists of twogenerations, including Carlton Gajdusek,Leonard Kurland, J. Kiffin Penry, andWilliam F. Caveness.

He is best known for leading the Na-tional Collaborative Perinatal Project, anationwide study of pregnancy and childdevelopment between 1959 and 1966.The study followed more than 50,000women from the time of their pregnan-cies until their children reached the ageof 8.

Dr. Masland was president of theAmerican Epilepsy Society and the NewYork Neurological Society. He was pres-

ident of the WFN from 1981 to 1989,bringing to developing countries the bat-tles against mental retardation, epilepsy,and head injury.

During his spare time, Dr. Maslandbuilt a 33-foot Herreshoff ketch. Helaunched the wooden sailboat in 1967and vacationed on it between Cape Codand the Chesapeake Bay for 30 years. Dr.Masland and his wife, Mary WoottonMasland, a speech and language pathol-ogist, had four children.

The Richard L. and Mary Masland Lecturewill be given by David Dodick, M.D., onOct. 30 at 8:00 a.m. He is professor ofneurology at the Mayo Clinic in Phoenix,Ariz., U.S.A. He is president-elect of theAmerican Headache Society and editor inchief of Cephalalgia.

—DIANA M SCHNEIDER, PH.D.,Public Relations Committee, WFN, and a

Member of the Board of the World Neurology Foundation.

A primary component of a World Congress of Neurology is the Named Ora-tions. They are funded by donations from their colleagues, held in trust ac-counts managed by the World Neurology Foundation. The Foundation andWorld Neurology have worked with the families of these truly remarkable hu-man beings to create brief biographies that explain why they are so honored bytheir colleagues. This year, all four speakers have donated their honoraria tothe Foundation for the purchase of tool kits as part of the 2009 Tool Kits forAfrica distribution for Uganda. The Foundation is seeking donations for its de-sired shipment to Nigeria for 2009.

Honorees in the WCN 2009 Named Orations

Dr. Yahr and colleague, Dr. Margaret Hoen

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LETTERSBoNT: Opinion vs. EvidenceWe were under the impression that rec-ommendations for treatment of neuro-logic disorders published in WORLD NEU-ROLOGY were evidence based. We weretherefore amazed to find the article by Dr.Stephen D. Silberstein on the safety andefficacy of botulinum neurotoxin, whichdid not seem to adhere to that expecta-tion (“BoNT for Headache: What YouNeed to Know,” December 2008, p. 4).

The first quarter of the article ad-dresses a 2008 evidence-based review bythe therapeutics and technology assess-ment subcommittee of the AmericanAcademy of Neurology (Neurology2008;70:1707-14).

The subcommittee recommendedthat BoNT injection probably is ineffec-tive in the treatment of episodic mi-graine (EM), that there is insufficient ev-idence to support or refute a benefit ofBoNT for the treatment of chronic dai-ly headache (CDH), and that BoNT in-jections should not be considered in pa-tients with EM and chronic tension-typeheadache (CTTH).

Dr. Silberstein then states that “basicscience data and clinical experience sup-

port a beneficial effect of BoNT in thetreatment of some types of headaches.However, data from clinical trials are in-conclusive (for CDH) or negative (forEM and CTTH).”

He questions the reasons for this dis-crepancy and spends the rest of the ar-ticle trying to explain it, citing study de-sign and patient- and treatment-relatedfactors.

The article ends with the comment,“my clinical experience shows thatsome headache patients benefit signifi-cantly from BoNT treatment,” then heannounces that BoNT is effective forchronic migraine in as yet unpublishedphase III trials.

This is not evidence-based medicineand such personal statements shouldcertainly be abandoned in general treat-ment recommendations. The authordisregards the data from systematic re-views and presents his personal viewsand explanations. Despite the negativeevidence, he advocates the use of BoNTfor headache.

Such a paper in the official publicationof the World Federation of Neurologywill encourage the widespread use of

Revisiting the Etiology of PMDIn his article “Individualize PsychogenicMovement Disorder [PMD] Diagnosis”(August 2009, p. 5), reporter Jeff Evanshas misunderstood the message I wastrying to get across about the way inwhich we think of PMD and communi-cate this to patients.

There are several ways of explainingthese symptoms to patients, including a“psychological” explanation which em-

Smoking May Speed Progression of MS in SomeB Y J E F F E VA N S


The clinical course and disease statusof multiple sclerosis patients ap-pear to be worsened by current

smoking, and in some cases, by the pastamount of smoking in former users, ac-cording to a cross-sectional survey andlongitudinal analysis of more than 1,400patients at one center.

“Although causality remains to beproved, these findings suggest that pa-tients with [multiple sclerosis] who quitsmoking may ... delay the progressionof MS,” wrote Brian C. Healy, Ph.D.,and his colleagues at Harvard MedicalSchool, Boston.

Two previous studies that have exam-ined whether cigarette smoking is asso-ciated with the progression of relapsing-remitting MS (RRMS) to secondaryprogressive MS (SPMS) or greater clini-cal disability arrived at opposing conclu-sions (Brain 2005;128:1461-5; Neurology2007;69:1515-20). But the substantiallylarger sample size of the present studygives it “more statistical power to assessthe relationship between smoking andMS progression,” the investigators wrote(Arch. Neurol. 2009;66:858-64).

In the current study, 1,465 MS patientscompleted a questionnaire about theirsmoking history. Overall, 257 were cur-rent smokers, 428 were ex-smokers, and780 were never smokers. The researchersused only smoking status at baseline intheir analyses, but any bias introduced bythis assumption “is likely small” becauseduring follow-up few patients startedsmoking for the first time (7) or stoppedsmoking (57).

The results of analyses derived frombaseline data showed that current smok-

ers had a significantly higher median Ex-panded Disability Status Scale (EDSS)score than did patients who neversmoked. The score in never smokers sig-nificantly increased with the number ofpack-years smoked. Current and ex-smokers were significantly more likely atbaseline to have a primary progressivecourse of MS, rather than an initially re-lapsing course (such as RRMS or SPMS),than were never smokers. The odds ra-tio for a primary progressive course was2.4 for current smokers and 1.9 for ex-smokers, both of which were adjustedfor age, sex, and disease duration.

The researchers also evaluated mark-ers of disease severity on MRI, whichwere not examined in previous reports.Current smokers had a significantly low-er brain parenchymal fraction on MRIthan did never smokers, although no dif-ference could be seen in the volume ofT2-weighted lesions between currentsmokers and never smokers. No differ-ence could be detected in brainparenchymal fraction between ex-smok-ers and never smokers, but ex-smokershad a significantly greater T2-weightedlesion volume than did never smokers.

In a longitudinal analysis of 891 pa-tients with median follow-up time of 3.3years, Dr. Healy and his associates ob-served a conversion from RRMS to SPMSin 20 of 154 current smokers, 20 of 237ex-smokers, and 32 of 500 never smokers.

The current smokers progressed signif-icantly faster from RRMS to SPMS thannever smokers. This risk did not changeappreciably after controlling for baselineEDSS score. The rate of conversion fromRRMS to SPMS, however, was similar be-tween ex-smokers and never smokers.

This finding “provides evidence thatthe adverse effects of smoking may be at

least in part reversed by quitting,” the re-searchers wrote.

At the end of 2 years and 5 years, theresearchers found no association be-tween smoking status and worsening ofEDSS score, regardless of the type of MSat baseline, after adjusting the analysesfor age at baseline, sex, disease duration,and treatment.

During follow-up on MRI, currentsmokers displayed significantly greaterworsening of T2-weighted lesion volumeand brain parenchymal fraction than didnever smokers. However, no differenceson these measures could be detected be-

tween ex-smokers or never smokers.The authors cautioned that because

they did not include healthy control sub-jects, they “could not determine the spe-cific effect of smoking on MRI measuresin patients with MS; some general con-sequences of smoking could have beenmistakenly attributed to MS progression.”

None of the researchers reported anyfinancial disclosures. They receivedfunding for the study from the PartnersMultiple Sclerosis Center, the NationalInstitute for Neurological Disordersand Stroke, and the National Institutesof Health. ■

Several recent studies, includingtwo meta-analyses (Curr. Opin. Neu-rol. 2007;20:261-8; and Ann. Neu-rol. 2007;61:288-99 and 504-13)demonstrated adverse influences ofsmoking on incidence and diseaseprogression in multiple sclerosis (ei-ther conversion from a first demyeli-nating event to clinically definite orfrom relapsing to chronic progres-sive MS). The current study by Dr.Healy and his associates adds tothese observations.

Although negative effects ofsmoking on MS progression are gen-erally moderate, they are of utmostimportance because smoking is theonly known modifiable MS risk fac-tor. But why or how does smokingharm MS patients?

Speculations on direct neurotoxic-ity or immunostimulation of mosttobacco components seem too sim-ple. Concepts from autoimmunerheumatic diseases point to a possi-

bly important pathogenetic effect ofposttranslational modification (e.g.,hydroxylation, citrullination, deami-dation, oxidation, methylation) ofproteins/ peptides that provoke im-munity to neo-antigenicity by “self-alteration”. Several inhaled noxiousfactors, including tobacco smoke,induce posttranslational modifica-tions that trigger immune reactionsto such modified autoantigens.

As with other environmental fac-tors, such as infections, it is likelythat such a vicious immunological cy-cle may depend on individual geneticsusceptibility. The future scientificchallenge will be to unravel the linkbetween environmental factors (suchas smoking) and (auto-) immunity.

—DR. THOMAS BERGER, head of the Neuroimmunological andMultiple Sclerosis Clinic & Research

Unit at the Innsbruck (Austria)Medical University.

C o m m e n t

BoNT in migraine and headache de-spite evidence for its inefficacy.

Peer Tfelt-Hansen, M.D., Rigmor Jensen,M.D., and Jes Olesen, M.D.

Glostru, Denmark

Dr. Silberstein replies:The results of a large phase III clinicalprogram evaluating botulinum neuro-toxin A versus placebo as headache pro-phylaxis in 1,384 adults with chronic mi-graine were scheduled to be presentedin September 2009 at the InternationalHeadache Congress in Philadelphia,U.S.A. (Cephalagia, in press). These dataprovide level 1 evidence of the effec-tiveness for botulinum neurotoxin Afor the prophylaxis of headaches inadults with chronic migraine.

phasizes a psychogenic etiology, and a“functional” explanation in which theemphasis is on mechanism (reversiblechange in function of the nervous sys-tem) rather than etiology.

These options also reflect differentways of thinking about the problem. Re-search using functional imaging (Brain2001;124:1077-90) and neurophysiology(Ann. Neurol. 2006;59:825-34) is chal-lenging the purely psychogenic view ofetiology that has dominated for over 100years.

The article implies that a “function-al” explanation is simply a useful deviceto keep a patient happy until they canaccept a purely psychogenic explana-tion. Using a “functional” explanation inthis way would be bordering on decep-tion. The point I had intended to getacross was that a functional explanation,as well as being easier for patients to un-derstand, may actually be better theo-retically as well.

Whilst psychological factors are un-doubtedly important in these symp-toms, the pure psychogenic etiologicalmodel may be wrong and in need of re-vision.

Jon Stone, Ph.D., FRCPEdinburgh, Scotland

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NEUROLOGY IN PRACTICE

Krasnoyarsk is the scientific center of Siberia, withKrasnoyarsk State Medical University, which isnamed after Prof. V.F. Vojno-Yasenetsky, forming

the hub of research, academic training, and clinicalpractice in the Krasnoyarsk Krai.

The field of neurology is particularly dynamic here.Numerous projects that are important for the devel-opment of neurological science, practice, and carehave flourished with help from the All-Russian Societyof Neurologists (ARSN) and specialists from the Kras-noyarsk State Medical University, elsewhere in thecountry, and from overseas.

There are 501 neurologists inthe region, with more than halfof them based in the industrialcities of Krasnoyarsk, Norilsk,Achinsk, and Kansk and Mi-nusinsk. The regional branch ofthe ARSN has a membership of343 pediatric and adult neurolo-gists, and the Krasnoyarsk Re-gional Society of Clinical Neu-rophysiologists has 61 members.

Annually, there are more than 10 training seminarsfor neurologists, several regional and interregionalneurological conferences, and at least one ARSN con-ference in Krasnoyarsk. There are many conferences onrehabilitation and epilepsy as well as teleconferenceswith neurological centers in Germany, Switzerland, andother countries.

TrainingMost of the region’s neurologists train at the Instituteof Postgraduate Education of Krasnoyarsk State Med-ical University in the departments of neurosurgery andneurology; neurology, which includes a course in tra-ditional medicine; and medical genetics and clinical neu-rophysiology. They can also train at other institutes inSiberia, Moscow, St. Petersburg, and other cities.

Programs for continuous medical education (CME)

have been implemented through the World Federationof Neurology and the education committee of theARSN. These programs are important as a means of de-livering educational materials and information aboutnew developments and advances in the specialty to allneurologists, especially those in remote areas. OnlineCME conferences, training seminars, and clinical analy-ses of difficult diagnostic cases in neurological practiceare important for postgraduate education of our neu-rologists and are carried out regularly.

Pediatric and Adult Care

As in other regions of Russia, there is a special systemof pediatric neurology in Krasnoyarsk Krai focusing ondiagnostics, prophylaxis, treatment, and rehabilitation inchildren and teenagers with the diseases of the nervoussystem. Generally, these neurologists are former pedi-atricians who have received special professional re-training or completed and internship in pediatric neu-rology and/or pediatric and adult neurology. Theywork in children’s outpatient departments and hospitals.

In Krasnoyarsk, there are specialized pediatric neu-rological wards only in children’s hospitals, with sepa-rate neurological departments for children aged 1-3years and aged 3-18 years. There are 40-60 beds in thesewards. Often, there is a demand for more beds, so theyare added as needed—though never more than 10. Onaverage, a neurologist working in the children’s wardstakes care of 20 patients a day.

The average length of a hospital stay for these chil-dren is about 2 weeks. In Krasnoyarsk Regional Chil-dren’s Hospital and in children’s hospitals of industri-al cities, the specialized neurological help is providedin the wards for internal medicine (and, if needed, forinfectious diseases). Neurologists in outpatient depart-ments examine about 24 children a day.

Adult patients with neurological diseases are treatedin the neurological wards in the hospitals and outpa-tient departments. Usually, they stay in the neurologi-cal departments for about 16 or 17 days.

Neurologists who work in outpatient departments andpolyclinics for adults in the rural districts of KrasnoyarskKrai see about 24-26 patients a day. Moreover, neurolo-gists also visit patients with acute neurological patholo-gy at home. Patients with brain trauma are treated in thedepartments of neurosurgery of big clinics or in the de-partments of surgery in central district hospitals.

From Isolation Centers to TelemedicineCompared with hospitals in Krasnoyarsk, neurologicalcare in more remote regions is of a lower quality as theyhave no modern diagnostic and laboratory equipment.

Historically, there are territorial isolation centers in thesettlements of central and eastern Siberia, where thereis a prevalence of hereditary disorders. So in an effort toimprove diagnostics, care, and education in neurology,the department of medical genetics and clinical neuro-physiology and the Centre for Medical Genetics werefounded in 2006 as part of the Institute of PostgraduateEducation at Krasnoyarsk State Medical University.

In Krasnoyarsk and Norilsk, the departments andwards are equipped with modern diagnostic techniques

comparable with those in Moscow polyclinics and oth-er big industrial cities in Russia. But these methods areavailable only in big hospitals. Krasnoyarsk is a vast re-gion, and patients in its remote rural areas are treatedin their local hospitals by specialists from the Krasno-yarsk Regional Clinical Hospital who travel to the ar-eas on an air medical service.

If necessary, seriously ill patients are transferred toneurological departments or the intensive care unit ofKrasnoyarsk Regional Clinical Hospital by air medicalservice or emergency ambulance. The most difficultsituation with emergency neurological care is in dis-

tant northern districts, becausethe connection with settlementsin winter is possible only by avi-ation and in summer, by rivertransport.

In the last 3 years, specialists atlarger hospitals in the region havebegun using telemedicine in theirconsultations for difficult-to-treatneurological patients and those inremote areas. In 2009, the region’s

ministry of health care introduced teleconsultations andteleconferences both in health care institutions and inremote rural hospitals. Key specialists from the Kras-noyarsk Regional Clinical Hospital, Krasnoyarsk StateMedical University, and specialized diagnostic centers inKrasnoyarsk participate in this form of care.

Subspecialty FocusNeurological science and practice in Krasnoyarsk focuson neurorehabilitation, epileptology, and neurogenet-ics. Krasnoyarsk is one of eight territories selected topilot a federal program aimed at improving stroke care.The Centre of Neurology and Neurorehabilitation,with its modern methods of rehabilitation, is one ofthose venues. Three hospitals—Krasnoyarsk RegionalClinical Hospital No. 1, Urban Hospital of Krasnoyarsk,and the Central Regional Hospital in Minusinsk— arepart of the program. A stroke-care register has beenstarted at Clinical Hospital No. 51 in Zheleznogorsk.

At the beginning of this year, the Centre of Epilep-tology, Neurogenetics, and Brain Research was estab-lished at the University Clinic at Krasnoyarsk State Med-ical University. Data on the epidemiology of epilepsyare being collected with guidance from specialists atRussian State Medical University in Moscow. This effortis seen as an important component in efforts to improvecare for patients with this disease. ■

BY NATALIA A. SHNAYDER, M.D., PH.D.

Dr. Shnayder is head of thedepartment of medical geneticsand clinical neurophysiology atthe Institute of PostgraduateEducation at Krasnoyarsk StateMedical University in theRussian Federation.

BY SEMEN V.PROKOPENKO, M.D., PH.D.

Dr. Prokopenko is headof the department ofneurology, also at theKrasnoyarsk State Medical University.

Krasnoyarsk Krai—“krai” means region orarea—is a federal subject of Russia. It is the

second largest territory of Russian Federation af-ter the Sakha Republic, occupying an area of903,400 square miles.

Krasnoyarsk Krai lies in the middle of Siberiaand belongs to Siberian Federal District, stretch-ing from the Sayan Mountains to the south alongthe Yenisei River to Taymyr Peninsula in thenorth. The administrative center of the region isthe city of Krasnoyarsk.

The most recent data (2002) put the population3,023,525. Most of the population is Russian,with the indigenous Siberian peoples making upno more than 1% of the population.

Krasnoyarsk Krai is an important industrial re-gion that includes the cities Krasnoyarsk, Norilsk,Achinsk, Kansk, Zheleznogorsk, and Minusinsk.

About the RegionEEG training in Krasnoyarsk State Medical University’sdepartment of genetics and clinical neurophysiology.

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A patient undergoes analysis of gait with simulationat the Krasnoyarsk Centre of Rehabilitation.

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A Thriving Specialty in Krasnoyarsk Krai

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Human African trypanosomiasis,which is also known as sleepingsickness, is a major killer disease in

36 countries in sub-Saharan Africa,where 60 million people are at risk forthe disease and up to 50,000 people dieannually from the infection.

Human African trypanosomiasis(HAT) is caused by protozoan parasitesof the genus Trypanosoma brucei, and istransmitted by the bite of the blood-sucking tsetse fly of the genus Glossina.

Although HAT was almost broughtunder control mainly as a result of ef-fective surveillancemeasures in the1950s, there havebeen several resur-gencies and epi-demics since then,with a steady increasein the number of cas-es, largely due to dis-ruption of social andsurveillance infra-structure, especially during successivewars in affected regions. However, thereis good evidence that the number ofnew cases is decreasing again because ofimproved patient surveillance.

Despite the fact that HAT is associat-ed with a very significant morbidity andmortality, it is one of the world’s “ne-glected diseases.” Drug treatment forHAT is outdated and highly toxic, andthis highly unsatisfactory situation re-flects the chronic lack of financial in-vestment from the developed world intonew drug development for both stages ofthe disease. If untreated, or inadequate-ly treated, the disease is invariably fatal.

There are two forms of the disease:East African HAT caused by Trypanosomabrucei rhodesiense (T.b. rhodesiense), andthe West African variant caused by T.b.gambiense, which accounts for about 95%of cases of HAT. The disease caused byrhodesiense has a faster tempo than gam-biense disease and leads to death if un-treated in several weeks to a few months,whereas the course of gambiense diseasemay last many months to years.

Two Stages and a Range of SymptomsThere are two stages of HAT, the early(stage 1), or hemolymphatic stage, whichoccurs 1-3 weeks after the initial insectbite, and then the late (stage 2), or en-cephalitic stage, when the parasites crossthe blood-brain barrier to enter the CNS(Ann. Neurol. 2008;64:116-26). In theearly stage, the parasites spread in thebloodstream, lymph nodes, and systemicorgans causing a variety of nonspecificsymptoms, including malaise, headache,arthralgia, headache, and fatigue. In-volvement of the heart, liver, spleen,skin, eyes, and endocrine system mayalso occur. Lymphadenopathy is typicalof gambiense disease.

The range of symptoms and signs dur-ing the late stage is very wide. In most cas-es, there is a characteristic sleep distur-

bance with alteration of the normalsleep/wake cycle with a constant urge tosleep, and polysomnography demon-strates sleep structure abnormalities.There may also be motor disturbances,such as pyramidal weakness, extrapyra-midal features, cerebellar ataxia, myelopa-thy, peripheral motor neuropathy, musclefasciculation, and also frontal lobe featuressuch as pout and palmarmental reflexes.

Sensory disturbances can also occur, asmay a variety of neuropsychiatric symp-toms. Various types of visual involvementhave also been described. Untreated or un-

successfully treated patients will rapidlydeteriorate with seizures, cerebral ede-ma, incontinence, and death. Typical au-topsy findings in such patients will showa widespread meningoencephalitis, an ex-tensive infiltration of cerebral white mat-ter with inflammatory cells and pathog-nomic Mott cells, which are plasma cellscontaining immunoglobulin M eosino-philic inclusions. Extensive data from bothpatients and a mouse model of the diseasehave implicated the key roles of pro- andcounterinflammatory cytokines, astrocyteactivation, and trypanosome-induced im-mune responses in causing the brain dam-age ( J. Clin. Invest. 2004;113:496-504).

No General Criteria to Aid DiagnosisSleeping sickness is diagnosed by identi-fying parasites in the peripheral blood orlymph node aspirates in the case ofrhodesiense disease, and by serologicalmeans using the Card agglutination try-panosomiasis test (CATT) in the case ofgambiense disease because in the lattercase, there are usually few detectableparasites in the blood.

There are no clinical suspicion criteriathat can reliably distinguish the two dis-ease stages, which may appear to mergeinto each other. All patients with provenHAT therefore require a lumbar punc-ture to examine the cerebrolspinal fluid(CSF) as that is the only current methodof diagnosing CNS involvement. Accu-rate staging of HAT is absolutely crucialbecause the drugs used for treating CNSdisease are so toxic. If drug treatment ismistakenly withheld from a patient whohas CNS disease then the patient will die,but giving highly toxic CNS drug thera-py for early-stage disease carries the highrisk of severe drug toxicity. This is one ofthe key dilemmas in managing patientswith sleeping sickness.

Unfortunately, there is no general con-sensus as to what criteria best define late-stage disease, and this is one of the most

problematic issues in HAT. The WHOcriteria for late-stage disease are the iden-tification of trypanosomes in the CSF ora CSF white blood cell count (WBC) ofgreater that 5/mcL. But not everyone ac-cepts this definition, and in West Africaa cutoff point of 20 CSF WBC/mcL isoften used. Others have suggested a com-promise figure of 10 WBC/mcL, but theactual presence of CSF trypanosomes isunequivocal proof that the CNS hasbeen invaded.

Although both CT and MRI scan ab-normalities have been shown in the fewpatients who have been studied in West-ern hospitals, such facilities are not avail-able in field conditions and are thereforeprimarily of value in investigating pa-tients who have recently returned fromAfrica. There are about 50 cases a year ofHAT diagnosed outside Africa, mainly inWestern travellers returning from vaca-tions to East African game reserves.

Toxic Drugs Hamper TreatmentDrug treatment of HAT is highly unsat-isfactory and essentially relies on the useof four drugs, none of which can be giv-en orally and which are so toxic that it isunlikely that they would have passedcurrently rigorous safety standards hadthey been introduced in recent years.

Early-stage rhodesiense disease is treat-ed with intravenous suramin, and early-stage gambiense disease is treated withintramuscular pentamidine. For late-stagerhodesiense disease, the only effectivedrug at present is intravenous melarso-prol (Mel B), a highly toxic arsenical drugthat was first used in 1949. It is given ei-ther as 2-4 courses of three times week-ly injections or, more recently, as a 10-daycourse of injections. Although melarso-prol is generally effective treatment forlate-stage HAT, in about 10% of patients,it is followed by a severe posttreatmentreactive encephalopathy (PTRE), 50% ofwhom will die. Melarsoprol treatmenthas an overall fatality rate of 5%, whichis remarkable.

The role of prophylactic corticosteroids

in preventing the PTRE is controversial, al-though I personally would prescribe them.An alternative drug for late-stage gambi-ense disease is eflornithine (DFMO),which was first shown to be effective in1981 but then became an “orphan drug.”Because of efforts by Médecin Sans Fron-tières, working closely with the WorldHealth Organization and the pharmaceu-tical industry, DFMO, which is expensive,was again made available for treatment ofHAT. Eflornithine is less toxic than melar-soprol, but needs to be given intravenouslyover 14 days, which is not always practicalin field hospitals. It is not without side ef-fects and completely ineffective for treat-ing rhodesiense infection. It has recentlybeen suggested that a combination ofeflornithine and nifurtimox is probably theoptimum drug treatment for gambiensedisease. After effective treatment, all pa-tients with HAT require regular follow-up,but this can be neither easy nor feasible.

What are the prospects for better di-agnosis and treatment of sleeping sick-ness? Despite many decades of underin-vestment in HAT, there is now anincreasing awareness of the importanceand seriousness of the problem with in-creasing financial input from the devel-oped world including from the Bill andMelinda Gates Foundation, WHO, theU.S. National Institutes of Health, andthe Wellcome Trust.

Looking Toward an Ideal SolutionFor better diagnosis, a rapid, user-friend-ly, inexpensive, reliable, and preferablynoninvasive method of staging for bothtypes of HAT is urgently needed. Thereare no new treatment drugs on the hori-zon and a promising oral drug for ear-ly-stage disease, DB 289, has been with-drawn near the end of a phase III clinicaltrial because of unexpected liver and re-nal toxicity. What is required, ideally, isa safe, inexpensive, oral drug that is ef-fective for both early- and late-stageHAT. Such an advance would obviatethe current dilemmas associated withCSF diagnosis of late-stage disease. ■

Every aspect of the disease—diagnosis, staging,therapy, follow-up—presents a unique challenge.

Sleeping Sickness: Africa’s ‘Neglected Disease’

BY PETER G.E. KENNEDY M.D., PH.D., D.SC.

Dr. Kennedy is the Burton Chair ofNeurology and head of the Division ofClinical Neurosciences at the Universityof Glasgow, Scotland, and an honoraryconsultant neurologist at the Institute ofNeurological Sciences, SouthernGeneral Hospital in Glasgow.

There have been several resurgencies in HAT since the 1950s, largely due todisruption of social and surveillance infrastructure, especially in war-torn regions.

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04_5_8thru13wfn9_9.qxp 9/10/2009 2:45 PM


Calendar ofInternational Events200919th World Congress of Neurology Oct. 24-30Bangkok, Thailandwww.wcn2009bangkok.com

European Charcot Foundation University Classes in MultipleSclerosis VI Nov. 11Lisbonwww.charcot-ms.eu

European Charcot FoundationSymposium: A New Treatment Erain Multiple SclerosisNov. 12-14Lisbonwww.charcot-ms.eu

The Sixth International Congresson Vascular DementiaNov. 19-22, 2009Barcelonawww.kenes.com/vascular

XVIII WFN World Congress onParkinson’s Disease and RelatedDisorders Dec. 13-16Miami Beach, U.S.A.www.kenes.com/parkinson

20103rd International Congress on Gait& Mental FunctionFeb. 26-28Washington D.C.www2.kenes.com/gait/pages/home.aspx

3rd International Conference onHypertension, Lipids, Diabetes &Stroke PreventionMarch 4-6Berlinwww.kenes.com/strokeprevention

6th World Congress ofNeurorehabilitation (WCNR2010)March 21-25Vienna www.wcnr2010.org/

14th Congress of the EuropeanFederation of NeurologicalSocietiesSeptember 25-28, 2010Genevawww2.kenes.com/efns2010/Pages/home.aspx

7th World Stroke CongressOct. 13-16, 2010Seoulwww2.kenes.com/Stroke2010/Pages/Home.aspx

European Headache and MigraineTrust International CongressOct. 28-31www2.kenes.com/ehmtic/Pages/Home.aspx

World Stroke Day: What You Can Do B Y J E YA R A J D. PA N D I A N, M . D.

The incidence of stroke is a globalhealth problem. It is the leadingcause of adult disability and the

second leading cause of mortalityworldwide.

A recent review of stroke incidenceand case fatality from 21 days to 1month post stroke showed a divergent,statistically significant trend in stroke in-cidence rates over the past 4 decades,with a 42% decrease in stroke incidencein high-income countries and a greaterthan 100% increase in stroke incidencein low- to middle-income countries.

During 2000-2008, the overall strokeincidence rates in low- to middle-in-come countries have, for the first time,exceeded the level of stroke incidence inhigh-income countries by 20% (LancetNeurol. 2009;8:355-69). In developingcountries, stroke affects individuals inthe most productive part of their liveswhere the average age of stroke patientsis 15 years younger than that in high-in-come countries.

Stroke treatment has shown rapidadvances. Proven therapies includemanagement of acute stroke patients ina stroke unit, intravenous thrombolysiswith recombinant tissue-type plas-minogen activator (rTPA), use of aspirinwithin 48 hours and decompressivesurgery for malignant middle-cerebralartery infarction. Effective measures for

secondary prevention are the use of an-tiplatelets, warfarin in atrial fibrillation,endarterectomy for carotid stenosis,and cholesterol reduction.

Among the various strategies, rapiddiagnosis, implementation of early pre-ventive treatment, early recognition ofcomplications and mobilization im-prove the overall outcome of these pa-tients. Management of these patients inacute stroke care units has a greater im-pact at community level than do othertreatments such as aspirin and rTPA(Lancet 2008;371:1612-23).

Stroke care services are not uniform-ly developed across the world. Even indeveloped countries, a small proportionof patients receive thrombolysis. In de-veloping countries, well-organized strokeand emergency transport services arelacking, many treatments are unafford-able, and sociocultural factors may in-fluence access to care. Moreover, publicawareness of stroke is lacking in both de-veloped and developing countries.

The World Stroke Day proclamationwas issued 2004 at the World StrokeConference in Vancouver. It was re-launched in 2006 at the Stroke Confer-ence in Cape Town when the Interna-tional Stroke Society and the WorldStroke Federation merged to form a sin-gle organization, the World Stroke Or-ganisation (WSO). Since then, WorldStroke Day is held each year on Octo-ber 29—on the “birthday” of the WSO

(Stroke 2008;39:2407-20).The WSO promotes World Stroke

Day to raise awareness of stroke—apreventable and treatable catastrophe.The theme this year “Stroke—WhatCan I Do?” This question implies thateveryone can do something aboutstroke. Individuals can learn their riskfor stroke and do something about it;they can learn the symptoms of strokeand what to do about them; and theycan help advance the stroke cause inmany other roles: as physician, nurse,health care professional, patient, care-giver, donor, business person, citizen,volunteer, policy maker, or member ofgovernment. The theme has been de-veloped to prompt action against strokeat the personal, family, or group level.

This year, we are encouraging peopleto run World Stroke Day events. TheWSO will be delivering tools, such aslists of ideas for activities and media re-leases. There will also be awards for thebest, most innovative activities to rec-ognize efforts that heighten strokeawareness. To register your interest inrunning a World Stroke Day event, sendan e-mail to [email protected] visit www.world-stroke.org. ■

DR. PANDIAN is professor of neurologyand head of research at the Betty CowanResearch and Innovation Centre atChristian Medical College in Ludhiana,India.

The Multiple Sclerosis InternationalFoundation aims to stimulate and fa-

cilitate international collaboration inresearch to better understand the natureof MS, develop better treatment and re-habilitation of people with MS, and in-form relevant communication and ad-vocacy initiatives.

Through the International Medicaland Scientific Board, the MSIF focuseson a number of research programs andactivities to achieve this aim.

We offer several awards for research inMS. In 2007, we launched the McDonaldFellowships, which enabled five young re-searchers from developing countries tocarry out a 2-year research project at anMS center of excellence. Another threefellowships were awarded in 2008. Alsolast year, we awarded seven Du PréGrants for researchers to learn new skillsthrough collaborative research projects,we launched the International ResearchMeeting Grants (www.msif.org/en/re-search/msif_research_awards/index.html) and we supported the 9th GordonConference on “Development and Dis-eases of Myelin” in Lucca, Italy.

From 2005 to 2007, MSIF collaboratedwith the World Health Organization togather data from 112 countries on theepidemiology of MS and the availabilityand accessibility of resources to diag-nose, inform, treat, support, and reha-bilitate people with MS. The Atlas of MSpublication and new Web site were

launched in September last year at theWorld Congress on Treatment and Re-search in MS in Montreal. It raises aware-ness and encourages exploration of thevalidity and robustness of data on epi-

demiology and services for people withMS (www.atlasofms.org/index. aspx).

We have also commissioned a reportinto the global economic impact of MS,containing data on the personal, social,and economic costs of MS for use inraising awareness of the impact of MSand argue for the allocation of scarce re-sources for the benefit of individuals,communities, and society as a whole.

The MSIF Research Alumni Pro-gramme was launched in April 2008 tofoster a lifelong relationship between re-search alumni and MSIF, and promotescientific communication and forma-tion of a global MS research network.We have 36 alumni (www.msif. org/en/research/msif_research_alumni/in-dex.html).

In 2008, we developed a Member So-

ciety Research funding database withdata on annual MS research funding byour member societies to help us and ourmember societies determine globalfunding trends and patterns, inform fu-

ture research funding de-cisions, and develop in-ternational collaborativeinitiatives. This past sum-mer, we organized an MSResearch Coordinationmeeting that brought to-gether key players in theglobal MS medical andscientific community toreview global MS research

spending and anticipate and prepare forfuture challenges and opportunities.

Issue 13 of MS in Focus, on tremorand ataxia in MS, came out in March.Most issues of this biannual publicationare available free in English, German,and Spanish (www.msif.org/ msinfocus).We also published an online update ofMS: The Guide to Treatment and Man-agement, which now includes a newchapter on unconventional therapies.

We coordinate work of the Interna-tional Pediatric Multiple Sclerosis StudyGroup (IPMSSG) and facilitated andpart-funded the first research sympo-sium of this group in Toronto, Canada,in April this year (www.ipmssg.org).

Finally, we were instrumental in settingup and coordinating global activities ofthe first World MS Day on May 27. ■

Foundation’s Quest for Global MS Awareness

BY ALAN THOMPSON, M.D.

Dr. Thompson is chair of theMSIF International Medical andScientific Board. He is director ofthe Institute of Neurology at theUniversity College London.

09_12_16thru20wfn9_9.qxp 9/10/2009 3:02 PM

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For free new Developments in Migraine Therapy podcasts, go to www.clinicalneurologynewsnetwork.com/migraine or subscribe by downloading iTunes® media player free from iTunes.com, select ‘Podcasts,’ and enter ‘Developments in Migraine Therapy’ into the Podcast Directory search field.

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04_5_8thru13wfn9_9.qxp 9/10/2009 2:50 PM


neurology specialists, and researchers. For the first time, the revision process

will be fully transparent. A beta draft isexpected in 2011, and it will be field test-ed at various sites around the world forfeasibility, reliability, clinical utility, andvalidity. Committee members will beseeking and choosing these sites overthe next half year. The penultimatedraft will be posted on the WHO Website, and interested parties and the pub-lic will be invited to respond. It is hopedthat the final version will be submittedto the World Health Assembly in 2014.

Advances in neurogenetics, molecularbiology, neuroimmunology, and otherfields have prompted dramatic changesin disease classifications. Categories ofdisorders once classified by clinical phe-

notype, for example, have been reshuf-fled to reflect their specific genetic caus-es, new disorders have been discovered,and some diagnostic categories havebeen redefined to reflect new under-standing of their causes and risk factors.Many hope computerized health datamanagement will facilitate more fre-quent remodeling of the ICD-11 codesto keep up with the growth of neuro-scientific and clinical knowledge. Theabsolute need to track epidemiologicaldisease data over time requires eachmodification of the ICD to be “map-pable” onto the previous version, a func-tion simple for computers but highlycomplex for those devising each newclassification. (See http://who.int/clas-sifications/icd/en.) ■

Focus on Disease ClassificationICD-10 • from page 1

MEETING UPDATE

AOAN Elects PresidentAt Delhi Congress

The 12th Asian and Oceanian Con-gress of Neurology and the Asianand Oceanian Association of Neu-

rology meeting were held in October2008 in New Delhi, India.

At that meeting, I was elected the13th president of the Asian and Ocean-ian Association of Neurology (AOAN).I would like to thank everyone for theirparticipation and support during the

meeting. I look forward to serving theassociation during my tenure. I hope tokeep members connected by sendingout regular newsletter updates, and Iencourage you to visit our new Website at http://www.aoan-neuro.org/.

Also at the meeting, Dr. William Car-oll of Australia was elected vice-presi-dent and Dr. Man Mohan Mehndiratta(India) secretary treasurer. The com-mittees will be headed up by Dr.Lawrence Wong of Hong Kong (edu-cation); Dr. Mohammad Wasay, Pak-istan (research); and Dr. Mehndiratta(membership). The regional director forthe World Federation of Neurology isDr. Amado San Luis of the Philippines.

The AOAN was founded almost 50years ago after Dr. Charles M. Posner, aWFN representative, toured the regionand suggested neurologists form an as-sociation to foster the advancement andexchange of neuroscientific informa-tion within the region. Dr. Shigeo Oki-

naka invited neurologists to a planningmeeting in Tokyo, Japan, and the asso-ciation was established on June 26, 1961.

The statutes stipulate that the Asianand Oceanian Congress of Neurology(AOCN) be held every 4 years.

On Sept. 14, 1962, the association’sboard was chosen, and it included rep-resentatives from Australia, HongKong, India, Japan, Korea, New

Zealand, Philippines, the Re-public of China (Taiwan), andThailand. The AOCN inaugur-al was held in October 1962 inTokyo, under the leadership ofDr. Okinaka.

Membership has increasedover the years from the initial 9member countries to the current18. Current members are Aus-tralia, Hong Kong, India, Japan,

South Korea, New Zealand, Philippines,Malaysia, Pakistan, Saudi Arabia, Israel,Indonesia, Singapore, Sri Lanka, Tai-wan, Thailand, and Mongolia—withVietnam recently becoming the 18th.

The founding AOAN mission state-ment, as proposed by Dr. Carroll, is to:� Promote development of clinicalneurology and neurological science inthe Asian and Oceanian region;� Assist, as required, in the develop-ment of training programs and re-search efforts in member and potentialmember nations of the region;� Facilitate cooperative exchange pro-grams for trainee and qualified neu-rologists and neuroscientists;� Participate with activities promotedby the WFN;� Respect the aims and aspirations ofmember organizations in providingsupport and advice; and� Promote friendship among regionalneurologists and neuroscientists. ■

BY CHING-PIAO TSAI, M.D.

Dr. Tsai is professor andsection chief at the Neuro-logical Institute at theTaipei Veterans GeneralHospital and NationalYang-Ming University inTaipei, Taiwan.

FROM THE LANCET NEUROLOGY

In Some, DBS ImprovesDystonia-Choreoathetosis CP

Bilateral pallidal deep brain stimula-tion may hold promise as a treat-ment for some patients with dys-

tonia-choreoathetosis cerebral palsy,according to results of a small pilot studyreported by Marie Vidailhet, Ph.D., ofGroupe Hospitalier Pitié-Salpêtrière,Paris, France, and her colleagues in theFrench SPIDY-2 Study Group.

Dystonia-choreoathetosis cerebral pal-sy (CP) is a form of CP characterized bysevere disabling movement disorderswith little or no spasticity and little or nocognitive impairment.

“This is the first demonstration that BP-DBS [bilateral pallidal deep brain stimu-lation] can im-prove patientswith this type ofCP. So far, nodrug or therapyhas proven to beeffective. Themodest improve-ment in this pilotstudy is the be-ginning of a newera for patientswith CP,” said se-nior author Dr. Pierre Pollak of JosephFourier University Hospital in Grenoble,France (Lancet Neurol. 2009;8:709-17).

BP-DBS is effective for patients withprimary dystonia, which encouragedthe investigators to study the proce-dure in dystonia-choreoathetosis CP.The multicenter prospective pilot studyenrolled 13 adults with dystonia-choreoathetosis CP with no cognitiveimpairment, little spasticity, and onlyslight abnormalities of the basal gangliaon magnetic resonance imaging. Pa-tients were treated with neurostimula-tion of the internal part of the globuspallidus for 1 year and then evaluatedfor improvement in movement, func-tional disability, pain, and mentalhealth–related quality of life.

The mean improvement on the Burke-Fahn-Marsden dystonia rating scale was24%, which is about half of the magni-tude of mean improvement achieved byDBS in primary dystonia (about 52%).Patients also showed improvements inbody pain (P = .04), emotional role (P=.06), and mental health (P = .05), withno deterioration in cognition or mood.

One-year outcomes on the Burke-Fahn-Marsden dystonia rating scale werevariable in the 13 patients, with 3 show-ing no improvement, 5 showing someimprovement (2 in the same range as inprimary dystonia—greater than 50% im-provement), and 5 only mildly improved(less than 50% on the rating scale). Theinvestigators sought to determine char-acteristics associated with improved out-come, but Dr. Pollak said that is difficultwith such a small number of patients.

“Placement of the electrodes is very im-

portant. The two patients who did the besthad optimal placement and stimulation ofthe globus pallidus internus, whereas theresults were poorer in patients whose elec-trodes were implanted suboptimally—2 or3 mm outside the globus pallidus inter-nus—spreading the electrical current be-yond the target site,” he explained.

Another factor for success seemed tobe patient selection. Those with mobiledystonia seemed to do better than thosewith static dystonia, though that obser-vation needs to be validated by furtherstudy, he noted. Future steps are to reim-plant the electrodes in four of the five pa-tients with poor outcomes and subopti-

mal placementof electrodes. “Ifthey improve,then this will bea strong argu-ment that place-ment of elec-trodes is acritical factor forsuccess.”

The investiga-tors plan to con-tinue to study

the 13 patients using formal scales and toimplant more CP patients outside of atrial setting. “It may be possible to extendBP-DBS to patients with some intellec-tual impairment and abnormal move-ment. We have operated on one patientwith an intellectual deficit and some ab-normal movements. This procedure issafe for cognition but won’t improve it,so we can propose stimulation of theglobus pallidus internus for patients withsevere dystonia and some intellectualimpairment,” Dr. Pollak said.

In an accompanying editorial, Dr. Stef-fen Berweck of Children’s Hospital, Uni-versity of Munich, Germany, wrote thatthe “pilot study on BP-DBS is encourag-ing, but it remains a challenge to advisean individual patient with dystonia-choreoathetosis CP about whether toundergo this treatment.”

“BP-DBS was tested in a highly select-ed subgroup of patients with CP. We donot know in how many patients withinthe spectrum of CP this approach sig-nificantly improves health status. Wehave to be careful not to raise unrealis-tic hopes in patients and families,” he said(Lancet Neurol. 2009;8:692-3).

Dr. Berweck also noted that patientsshould be counseled that the after-carewill take several visits within the first yearafter implantation to optimize therapeu-tic effects through adjustment of stimu-lation parameters. The decision to havethis procedure should be made betweenthe physician and the patient, he wrote.

— Alice Goodman

Ms. Goodman is a freelance writer for TheLancet Neurology.

DR. VIDAILHET DR. POLLAK

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7th WORLDSTROKE CONGRESSCOEX Center, Seoul, Korea, October 13-16, 2010

MAIN TOPICS:• Carotid Disease• Alternative Medicine• Primary Prevention• Subcortical Stroke• Advances in Neuroimaging• Stroke Burden in Asia• Organizing Stroke Care Services• Vascular Cognitive Impairment• Acute Revascularization• ABC Stroke Education Program• Public Awareness/Advocacy• Unrupture Aneurysm/AVM• Critical Care• Long Term Complications of Stroke

1-3 Rue de Chantepoulet, PO Box 1726, CH-1211 Geneva 1, SwitzerlandTel:+ 41 22 908 0488; Fax:+ 41 22 906 9140; E-mail: [email protected]: www.stroke-congress.com

© Kenes International 2009. All rights reserved.

C o n g r e s s O r g a n i z e r s

WSC 2010 provides leading medical

professionals with future strategies to

improve the care of stroke victims.

Join the challenge to combat the

second most common cause of

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StrokeA Preventable and Treatable Disease

www.stroke-congress.comAbstract Deadline: April 12, 2010


C o m m e n t

Influenza A and B viruses are known tocause encephalitis or encephalopathy, butthey are rare complications. It is assumedthat influenza virus causes neurologicalsymptoms in two main ways: first, by directinvasion of nervous tissue, usually pre-senting with neurological manifestationswithin 4 days of onset—classified as en-cephalitis—or second, by an immune re-action affecting nervous tissue that usual-ly presents with neurological manifestations

5 days after the onset of the infection—classified as encephalopathy. However, vi-rological evidence is rarely documented inthe CSF.

The neurological manifestations varyfrom mild cases of transient cortical dys-function, such as excessive sleep, stupor,hallucination, inappropriate behavior, andseizure (with or without fever) to severe cas-es of necrotizing encephalitis with neuro-logical sequelae or even death. Clinicians

caring for children should remain vigilantfor this complication of influenza virus in-fection. Influenza virus–associated CNSdysfunction may be more common thanpreviously recognized, but the prognosis isnot always grave.

—DR. YHU-CHERING HUANG,division of pediatric infectious diseases at

Chang Gung Children’s Hospital and ChangGung Memorial Hospital, Kweishan, Taiwan.YHU-CHERING

HUANG, M.D., PH.D.

seizure and subsequent postictal mentalstate. While he was hospitalized, hehad a 30- to 40-minute partial complexseizure. Brain magnetic resonanceimaging was consistent with en-cephalopathy.

A third child, a 7-year-old white malewith a history of febrile seizures, pre-sented to the emergency room follow-ing a seizure, 2 days of cough, nasal con-gestion, and fatigue. A brain MRIshowed nonspecific white matter ab-normalities, and localized cerebral dys-function was evident on electroen-cephalography.

The fourth patient, a black male aged11 years with a history of asthma, hadfever, fatigue, headache, abdominal pain,and vomiting. Neurological examina-tion of this patient revealed ataxia. Healso had a seizure after hospital admis-sion and later experienced visual hallu-cinations. He had difficulty respondingto questions and required supplementaloxygen. An electroencephalograph wasconsistent with encephalopathy, but aCT scan was normal.

Antiviral therapy included oseltamivirin all four patients and rimantadine in allbut the 11-year-old. All four children re-covered fully, with no neurological se-quelae at discharge.

This is the first report of patients withneurological complications of the H1N1influenza virus infections. The severityof the complications in these four pa-tients was less than described in two pre-vious studies of neurological complica-tions associated with seasonal influenza,which have included reports of severestatic encephalopathy and death.

The frequency of neurological com-plications with pandemic flu is notknown, but it is likely that additional cas-es in children will be reported as the pan-demic continues, especially because chil-dren appear to be infected with theH1N1 virus more often than adults, theCDC noted.

The center also added that antiviraltreatment should be initiated as soon aspossible for any patient who is hospi-talized with neurological symptomsand suspected influenza infection ofany type. ■

Jeff Evans contributed to this report.

Antiviral TimingMay Be Key

H1N1 • from page 1

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The World Federation of Neurolo-gy’s mission is to advance researchand the standard of neurological

practice. The dawning of our informa-tion age and our escalating ease of trav-el have reconfirmed with unambiguousclarity, that national boundaries are ir-relevant to science and dis-ease and that sharing experi-ence and knowledge can addvalue to all.

From the beginning oftime, the House of Medicinein every region of the worldhas existed in an unstableequilibrium with the scientif-ic, religious, social, political,and economic concerns ofthe day. We do not differ from our pre-decessors in having to embrace thesechallenges, and in doing so, we merelydefine one component of the work towhich we have dedicated our lives. Thiscommitment to the greater good, a con-spicuous necessity for doctors in thepast and at present, will undoubtedlycontinue to be required of every futuregeneration.

Similarities Amid ChallengesA life in medicine has always been mean-ingful and captivating, summoning fromits devotees the most noble of humanqualities, and it is neither self-serving norarrogant to believe that this has neverbeen more engrossing. Yet these chal-lenges continue, and despite vast andspecific regional and national differences,many similarities exist.

For example, economic circumstancesaffect each of us differently. Local op-portunities for physician research andtraining and the manner in which we areable to administer to patients vary formany additional reasons, including thedisparities in the ratio of physicians topopulation size.

Is there a universal theme enmeshedin these challenges? Is there a soft un-derbelly of health care delivery, re-search, and education? What is thebreaking point? And if there is, willdefining and understanding it empow-er physicians and strengthen our entryinto health care debates around theworld?

I believe that all of these threats im-peril the behavioral attributes of thedoctor and are felt most on our charac-ter, which has been developed over cen-turies giving birth to the philosophy orethos of doctoring. Our ethos is the uni-versal, its application, of course, vary-ing from country to country and fromtime to time. It is our responsibilityalone to inform our policy makers ofthis.

The physician’s charter is consideredby many to be the basis of medicine’scontract with society, and it requires our

commitment to competence, respect,education, and collaboration and that wepromote access to care (“Medical Pro-fessionalism in the New Millennium: APhysician Charter” [Ann. Intern. Med.2002:136:243-6]). Yet this is not enough;the charter is about our behavior and not

the most significant component of ourprofessionalism and the principal influ-ence on our motivation and behavior,our ethos.

The philosophy of doctoring closelyresembles the Greek concept of eudai-monism, first discussed by Socrates. Thishas led to the development of content-ment theory and the concept of the op-portunity for human flourishing. Hu-man flourishing is not a consequence ofhonor, wealth, or power; rather, it flowsfrom rational activity in a complete ormeaningful life, filled with virtues ofcharacter, such as honesty, integrity, per-sonal responsibility, intellect, and rationaljudgment. Many consider this search forcontentment inherent in humans as so-cial animals after satisfying our basic sur-vival drives. Contentment theory is nowa component of economic and socialplanning in many countries, and the va-lidity of incorporating this thinking hasbeen confirmed by economists, philoso-phers, psychologists, and more recently,biologists.

A Larger Humanistic WholeMedical care quality is jeopardized whencontentment theory is not a componentof health policy decisions, and the im-pact of its absence is borne predomi-nantly by our ethos. In defending ourethos, we as biologists and neurologistsin particular, are strengthened by emerg-ing concepts in neuroscience research,which provide a window to our behav-ior and confirm that doctrinaire eco-nomic and social planning, when notpart of a larger humanistic whole, issuboptimal.

This necessity for concurrent eco-nomic and social planning is suggestedby human capability on a preconceptu-al cellular level to recognize expecta-tions, intentions, and motivation (Riz-zolatti, G., Sinigaglia, C., Anderson, F.,“Mirrors in the Brain,” New York: Ox-ford University Press, 2008) and also,value, utility, and numerosity (Nature,1999;400:233-8). We also understand thatmeaningful planning can lead to new

Is There a Universal Theme Underlying theChallenges to Medicine?

BY STEPHEN M. SERGAY, M.B. B.CH.

Dr. Sergay is immediate past-president American Academyof Neurology and immediatepast–North American RegionalDirector of the WFN. He is ageneral neurologist practicingin Tampa, Florida, U.S.A.

long-term memory formation and thuslasting behavior modification. Eric Kan-del defined both the molecular basis oflong-term memory formation by thesynthesis of a new mRNA and protein,and its epigenetic impact on our genome(“In Search of Mind,” New York: W.W.Norton & Co., 2006). Our understand-ing of epigenesis, reflecting in part theconsequences and the causes of our so-cial evolution, confirms our inescapableduty and responsibility to our larger ge-netic future, vastly different from eu-genics. Because of this, it is necessary forus to inform planners of their responsi-bility to consider the deeper conse-quences of their actions.

Defining Our EthosBut our ethos has not been fully defined,and it needs to be. It is not an abstrac-tion but rather a set of behavioral prin-ciples that determine how we respond tothe sick. It is our character, behavioralcharacteristics, internal motivators,physician-patient relationship require-ments, the ethics of our professionalism,and our guardianship of appropriate au-tonomy for physicians and patients. Ourethos has not been, nor will it be, forev-er impenetrable, and therefore our def-inition must incorporate integrity tocounter human weaknesses such as envy,

greed, and power. Preeminently, our de-finition must include personal responsi-bility, because if we do not accept re-sponsibility, we will surrender ourresponsibility to others.

Societal complexity requires morethan one method of dialogue in healthcare policy debates. It is our responsibil-ity to speak for the House of Medicine.We must sit at the negotiating table, notas agents of the government, politicians,economists, or managers of the prob-lems created by uninformed policy. Wewill be most effective when, conversantwith the details of our medical philoso-phy, we become the voice of our ethos,and educate our politicians and econo-mists in advance of their decision mak-ing, of the potential impact of theirplanning on those who deliver medicalservices and those whom we serve, ourpatients. We must work to encouragepolicies that strengthen and not thosethat weaken our ethos, because of ourbelief, that by so doing, the health carewe plan for will have a greater chance ofspawning better quality research, edu-cation, and care delivery, all performedmost cost effectively. ■

Adapted from Neurology, Sergay S.M.,“Doctoring 2009: Embracing theChallenge. Neurology” (in press).

Dr. Edgard B. Ngoungou from Li-breville, Gabon, received the 2009

Bruce S. Schoenberg InternationalAward in Neuroepidemiology fromDr. Joseph Zunt of the University ofWashington, Seattle, at the annualmeeting of the American Academy ofNeurology in Seattle, U.S.A.

He presented the results of an epi-demiologic study on the role ofmalaria infection in causing epilepsyin Africa. The study was conducted

with the cooperation of the Instituteof Neuroepidemiology and TropicalNeurology in Limoges, France.

During the past 25 years, theWFN’s Research Group on Neuro-epidemiology has held a 1-day annu-al meeting concurrently with theAAN meeting. Beginning in 1984, theabstracts of the invited lectures, pa-pers, and posters presented at the an-nual meeting have been published inthe journal, Neuroepidemiology.

AAN Presents Award forNeuroepidemiology

CO

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A synopsis of the American Academy of Neurologypresident’s address in Seattle, U.S.A., April 2009.

09_12_16thru20wfn9_9.qxp 9/10/2009 3:04 PM

Leading resources in clinical neurology!

Volume 9 Issue 2 January 2008 ISSN 1389-9457

Editor-in-Chief:SudhansuChokroverty

Field EditorsR.P. AllenC. GuilleminaultP. LevyL. Ferini-StrambiO. Bruni

Associate EditorsR.P. AllenC. BassettiA. CulebrasR.A. FerberR. GrunsteinC. GuilleminaultJ. HednerW. HeningS. KatayamaP. LevyM. MahowaldJ. MontplaisirM. SandersM. ThorpyT. Young

Official Journal of the World Association of Sleep Medicineand International Pediatric Sleep Association

Official Journal of the European Paediatric Neurology Society

Volume 10, Number 1January 2006

SEIZURE

Volume 15, Number 8, December 2006 ISSN 1059-1311

The Official Journal of Epilepsy Action

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Vol. 131, Nos. 1–2 30 January 2007 ISSN 1566-0702

Clinical Neurologyand Neurosurgery

Volume 108, issue 7, October 2006 ISSN 0303-8467108(7) 621–720

ReviewNeuromuscular disorders in critical illness – L. Pandit, A. Agrawal (Mangalore, India) 621

Original articlesLaterality does not influence early mortality in MCA ischemic stroke – I. Mateo, A. Pinedo, I. Escalza, J.C. Garcia-Monco (Vizcaya, Spain) 628Vascular cognitive impairment in patients with late-onset seizures after an ischemic stroke – J. De Reuck, M. De Clerck, G. Van Maele

(Ghent, Belgium) 632Cardiovascular risk factors in patients aged 85 or older with ischemic stroke – A. Arboix, M. Miguel, E. Císcar, L. García-Eroles,

J. Massons, M. Balcells (Barcelona, Spain) 638The interleukin-10 levels as a potential indicator of positive response to interferon beta treatment of multiple sclerosis patients –

H. Bartosik-Psujek, Z. Stelmasiak (Lublin, Poland) 644Medically refractory epilepsy associated with temporal lobe ganglioglioma: Characteristics and postoperative outcome – A. Radhakrishnan,

M. Abraham, V.V. Radhakrishnan, S.P. Sarma, K. Radhakrishnan (Trivandrum, India) 648Alleviation of intracranial air using carbon dioxide gas during intraventricular tumor resection – T. Beppu, K. Ogasawara, A. Ogawa

(Morioka, Japan) 655Clinico-pathological and immunohistochemical characteristics associated to recurrence/regrowth of craniopharyngiomas – M.L. Tena-Suck,

C. Salinas-Lara, R.I. Arce-Arellano, D. Rembao-Bojórquez, D. Morales-Espinosa, J. Sotelo, O. Arrieta 661

Case reportsRespiratory failure in a patient with antecedent poliomyelitis: Amyotrophic lateral sclerosis or post-polio syndrome? – S.-i. Terao, N. Miura,

A. Noda (Aichi, Japan), M. Yoshida, Y. Hashizume, H. Ikeda, G. Sobue (Japan) 670Bilateral C5 motor paralysis following anterior cervical surgery—a case report – K.S. David, R.D. Rao (Milwaukee, WI, USA) 675Correlation of magnetic resonance images with neuropathology in acute Wernicke’s encephalopathy – Y.-T. Liu, J.-L. Fuh, J.-F. Lirng, A.F.-Y. Li,

D.M.-T. Ho, S.-J. Wang (Taipei, Taiwan) 682Subacute aseptic meningitis as neurological manifestation of primary SjÖgren’s syndrome – R. Rossi, M. Valeria Saddi (Nuoro, Italy) 688Thin corpus callosum and amyotrophy in spastic paraplegia—Case report and review of literature – B. Winner, C. Gross, G. Uyanik,

W. Schulte-Mattler, R. Lürding, J. Marienhagen, U. Bogdahn (Regensburg, Germany), C. Windpassinger (Graz, Austria), U. Hehr, J. Winkler (Regensburg, Germany) 692

Camptocormia or Pisa syndrome in multiple system atrophy – J. S awek (Gdansk, Poland), M. Derejko (Warszawa, Poland), P. Lass, M. Dubaniewicz (Gdansk, Poland) 699

“Frontal variant Alzheimer’s disease”: A reappraisal – A.J. Larner (Liverpool, UK) 705Transient tetraplegia after cervical facet joint injection for chronic neck pain administered without imaging guidance – J.G. Heckmann,

C. Maihöfner, S. Lanz, C. Rauch, B. Neundörfer (Erlangen, Germany) 709Adie’s pupils in paraneoplastic ganglionopathy with ANNA-1 – J.V. Campellone, A. Hageboutros (Camden, NJ, USA) 712

Book reviewsHead injury: Pathophysiology and Management – D. Van Dam (Wilrijk, Belgium) 715

(Contents continued on OBC)

For a complete list of neurology products, detailed information on the titles above and online access to the journal articles, visit

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Autonomic Neuroscience: Basic and Clinical

Brain & Development

Clinical Neurology and Neurosurgery

Clinical Neurology News

Clinical Neurophysiology

Epilepsy & Behavior

Epilepsy Research

European Journal of Paediatric Neurology

European Journal of Pain

Experimental Neurology

Journal of Clinical Neuroscience

Journal of Neuroimmunology

Journal of the Neurological Sciences

Journal of Pain

Journal of Pain and Symptom Management

The Lancet Neurology

Neurobiology of Aging

Neuromuscular Disorders

Neuroscience & Biobehavioral Reviews

Neurotherapeutics (NeuroRX)

Pain

Parkinsonism and Related Disorders

Pediatric Neurology

Regional Anesthesia and Pain Medicine

Seizure: European Journal of Epilepsy

Sleep Medicine

Sleep Medicine Reviews

Surgical Neurology

The offi cial journal of the World Federation of Neurology THE journal for the prompt publication of studies on the interface between clinical neurology and the basic sciences.And did you know.. Journal of the Neurological Sciences is your ultimate resource for the latest developments and research on Vascular Dementia, Stroke and Multiple Sclerosis!

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OBITUARY

John Alexander Simpson (1922-2009)B Y P E T E R O. B E H A N, M . D.

Felix, qui potuit rerum cognoscere causas.Virgil, The Georgics, Book II

John A. Simpson, professor of neurology at the Uni-versity of Glasgow from 1964 to 1987, died in Mayat the Royal Infirmary in

Glasgow, Scotland, from a rela-tively acute illness. He was the es-teemed international authorityon myasthenia gravis and playeda major role in the modern de-velopment of neurosciences inScotland, particularly in Glasgow.

Iain, as he was known, camefrom a long Scottish lineage thatincludes the 18th century polit-ical cartoonist James Gillray.

He is a good example ofserendipity and major advancesin science. In 1960, while he helda Medical Research Council trav-eling fellowship at the NationalHospital for Nervous Diseases atQueen’s Square, London, he ob-served the increased associationof myasthenia gravis with other diseases, thought at thattime to be autoimmune in etiology. He published his hy-pothesis in the Scottish Medical Journal, and that paperis regarded as the seminal paper that directed researchinto the immunological etiology of myasthenia gravis.It was logical, therefore, that Iain should pursue his in-terest in neurology and head up the University of Glas-gow’s department of neurology, where the main re-search interest was muscle diseases.

He was appointed the James Watson Lecturer of theRoyal Faculty of Physicians and Surgeons of Glasgow, aHoneyman Gillespie Lecturer at Edinburgh, an AbbottLecturer at Newcastle, and later a fellow of the Royal So-ciety at Edinburgh. Other appointments included that ofhonorary consultant neurologist to the army, to the civ-il service commission, chairman of the Scottish Coun-

cil for the Neurological Servicesand of the Scottish Epilepsy Asso-ciation, and a member of the Re-search Committee of the MuscularDystrophy Group of Great Britain.

At the time he became head ofthe Glasgow department, therehad been enormous changes inthe structure of neuroscience inScotland—with the Institute ofNeurological Sciences being es-tablished at the Southern GeneralHospital in Glasgow, where Dr.Bryan Jennett, professor of neuro-surgery, and Dr. J. Hume Adams,professor of neuropathology, wereamong the main contributors.

Iain had come to Glasgow fromthe University of Edinburgh, wherehe had been chief of neurology and

had built up an active department with a sound reputa-tion. He was ideally equipped to develop neurology inGlasgow, and his department there became a showpiecein 1967 for the International Congress of Electromyog-raphy, a subject he excelled in and contributed to. Thiswas the beginning of many occasions when Iain and hiswife, Elizabeth, would generously entertain visiting neu-rologists and neuroscientists. Indeed, Iain’s kindness to ob-scure authors often had grateful individuals plan their

journey to include a visit to Glasgow and the Simpsons.Iain was a good general physician, and wrote and

studied not only on myasthenia gravis but the chorearelated to hypothyroidism, the dermatological alter-ations and hypocalcaemia, and several findings relatedto abnormal nerve conduction velocities. He wasamong the first who noted the neurophysiological ab-normalities of the Eaton Lambert Syndrome.

He was in demand to give many guest lectures, ac-cepted invitations to visit neurology departmentsthroughout Australia, India, Europe, and Japan, andcontributed to now classic textbooks of muscle andneurological disease. He also peer-reviewed severaljournals and had more than 94 original papers on neu-romuscular neurological diseases published.

He clearly was of the “old school” and looked after hispatients well. They became part of his family to the ex-tent that he could recount their marriages and achieve-ments. He was a kind, caring, decent fellow of whom itwas an honor to be considered one of his friends. He de-lighted in making a solid and sound diagnosis of ex-tremely rare diseases, and he imparted this knowledge sothat his students were, like Byron’s hero, wax to receiveand marvel to retain. Patients with myasthenia graviscould expect to see him at any time of the day or nighttaking as he did a personal interest in their treatment.

No account of Iain would be complete without de-scribing his addiction to and pleasure in sailing and Scot-tish fiddle music. He once told me that for him, thegreatest pleasures was drinking hot soup followed bya large quantity of malt whisky after a successful sail.

Iain left behind a department in excellent health, andhis advice and warm friendship will be sadly missed. ■

DR. BEHAN is professor emeritus of neurology at theUniversity of Glasgow.

FROM THE JOURNAL OF THE NEUROLOGICAL SCIENCES

Tracking Dementia Risk in Atomic Bomb SurvivorsB Y A L E X T S E L I S, M . D. , P H . D.

The effects of radiation on the brain arewell recognized from the experience

with radiation therapy to the brain incancer patients. Not much is knownabout these effects, but the basics areclear: Ionizing radiation breaks DNAmolecules, fragments RNA, generatesfree radicals, denatures proteins, andthus damages or kills cells.

Things become more complicated atthe multicellular level. Different cells havedifferent susceptibilities to radiation dam-age, they may be affected by or affectneighboring cells, they may acquire neo-plastic properties, and/or their loss or dys-function may or may not strongly affectthe organ (thus loss of neurons is moresignificant than that of hepatocytes).

Clinically, radiation damage to thebrain comprises several well-describedsyndromes in patients who are treatedwith radiation therapy. Acute, early-de-layed, and late-delayed encephalopathiesare all well-defined, if not completely un-derstood. The late effects are of particu-lar interest because they can tell us about

the basic mechanisms of neurodegener-ative diseases and generate epidemio-logic hypotheses.

Radiation necrosis can occur severalmonths or even years after radiationtherapy. Postradiation brain atrophy canbe accompanied by disabling cognitivedeficits. The radiation dosesin these patients are in therange of hundreds to thou-sands of centigrays, oftengiven in a sequence of frac-tions to minimize toxicity.What happens at lower ra-diation doses—can such syn-dromes arise years later witha slowed tempo? Can otherrelevant tissues be damagedwith very late effects?

An important examplewould be radiation vasculopathy. Mostoften, this is extracranial large-vessel dis-ease, a form of accelerated atherosclero-sis usually involving a carotid artery andresulting in cerebrovascular disease. Doesradiation predispose to the developmentof dementia—vascular or Alzheimer’s?

In an interesting paper, Dr. Michiko

Yamada and her colleagues described astudy in which they examined the risk ofdementia in survivors of the atomicbombings of Hiroshima and Nagasaki in1945. The researchers are based at theRadiation Effects Research FoundationAdult Health Study (RERF), a joint

Japan-United States researchorganization with laborato-ries in the two cities.

They estimated the radia-tion doses the subjects wereexposed to depended on thedistance from the explosionand shielding by the terrain.The subjects were then di-vided into three tertiles ofradiation dose with about500-800 subjects in eachgroup, serially evaluated for

cognitive problems, then assigned a di-agnosis of dementia classified as vascularor Alzheimer’s type. The radiation doseswere in the range of milligrays, roughlya tenth of the doses used for radiationtherapy ( J. Neurol. Sci. 2009;281:11-4).

The findings showed no increase in therisk of either dementia type with radia-

tion dosage, in the dose range to whichthe subjects had been exposed. The au-thors noted that the findings might havebeen subject to certain biases but that itsstrengths included its prospective, popu-lation-based nature. The findings were inline with results in other populations.

Dr. Yamada, a physician and epidemi-ologist, has been in charge since 1983 ofthe analysis of the RERF study to inves-tigate the long-term effects of exposureto radiation from the atomic bombblasts. The study is one of the largest andlongest-running cohort studies in theworld. Another study based on thesedata has shown no increase in the inci-dence and prevalence of Parkinson’s dis-ease in this population. An attempt to ex-amine a similar hypothesis foramyotrophic lateral sclerosis was unsuc-cessful because of the small number ofsubjects with the disease. ■

DR. TSELIS is an associate professor ofneurology at Wayne State University inDetroit, U.S.A. He is the book review editorfor the Journal of the NeurologicalSciences.

DR. MICHIKO YAMADA

Dr. John Simpson, renowned clinicianand researcher and valued colleague.

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MOVIE REVIEWS

Lyme Documentary Misleading, Perhaps Irresponsible“Under Our Skin,” directed by Andy

Abrahams Wilson

Why, you may ask, is there a moviereview in WORLD NEUROLOGY?A reasonable question.

“Under Our Skin” is a documentary-style film about chronic Lyme disease andthe debate surrounding it. With lovely cin-ematography and sobering music, it de-picts a number of clearly suffering patientsand the “Lyme-literate physi-cians” who have treated them.

The treating physicians areseen talking to their patientswith great empathy as they ex-plain the rationale for their ap-proach. We even see a patholo-gist who, mad scientist–like,applies molecular biologic tech-niques in a laboratory in hishome basement, studying awell-worn 1940s volume on syphilology.He reasons that “just as general paresis ofthe insane is indistinguishable fromAlzheimer’s disease,” Lyme disease canbe responsible for multiple sclerosis (MS),amyotrophic lateral sclerosis (ALS),Parkinson’s, and Alzheimer’s disease.

Of course, there are excerpted au-thoritative quotations and interviews—carefully edited—to support the film-makers’ premise. (Though the plot alsorequires villains, and unfortunately, Imake a cameo appearance in what re-sembles an array of wanted posters.)

Several experts were interviewed toprovide “balance.” For example, an in-ternationally respected infectious diseaseexpert states that few of the patients re-ferred to him for chronic Lyme diseasehave anything to suggest they ever hadthe infection; his 30-second excerpt is jux-taposed with a Simpson’s clip. Other ex-pert comments are rebutted—in one in-stance, by a psychiatrist who has given upthe practice of psychiatry to treat “chron-ic Lyme patients” with antibiotics, and inanother by the office manager of a“Lyme-literate physician.”

Finally, the authors who wrote the In-fectious Disease Society of America(IDSA) Lyme disease treatment guide-lines are repeatedly accused of beingtainted by conflicts of interest. This po-sition is bolstered by focusing on theConnecticut attorney general’s lawsuitthat alleged that the IDSA violated an-titrust law in promulgating its guide-lines. Not mentioned is the fact that thatthe lawsuit was settled with no finding

of either an antitrust violation or of anymeaningful conflicts of interest.

The movie continues with scenes ofmultiple legal proceedings in which themedical establishment and the IDSAauthors are portrayed as persecutingthe “ Lyme-literate physicians”—appar-ently either because all medical expertswant to help the health insurance in-dustry save money or because thesesupposedly conflicted physicians standto make windfall profits from patentsthey hold related to this disease [sic].

It would be easy to dismiss this film asartfully crafted propaganda; howeverthat would ignore its important lessons.As Dr. Bernard Raxlen (the antibiotic-wielding psychiatrist) says in the film,“Something funny is going on here.”

So what is it exactly?As the film makes obvious, there is a sig-

nificant population of patients who arenot satisfied with the diagnoses and treat-ment provided by conventional medicine.As they have sought a sympathetic ear,they have helped sustain a group of physi-cians who are apparently convinced theyhave unearthed both an unprecedented

illness and a conspiracy to conceal it.Of importance to the neurology com-

munity, is that these physicians—none ofwhom has any neurological expertise—have focused on what they perceive (in-correctly, in most instances) to be neu-rological manifestations of their patients’symptoms. This is terrifying for the pa-tients, who often become convinced thatthey have a progressive nervous sys-tem–destroying illness, which can only be

cured with these physicians’unique ministrations.

These physicians and theirsupporters argue that theIDSA guidelines ignored a“vast worldwide literature” insupport of “chronic Lyme dis-ease.” Curiously though,when they published theirown “evidence-based guide-lines,” they included no refer-

ences to anything except Class IV anec-dotal evidence substantiating theexistence of this entity, or validating pro-longed antibiotic treatment. In a contrastthat epitomizes the tension between ev-idence-based medicine and anecdotal ob-servation, a physician leader of thisgroup has defined evidence-based med-icine as “a treatment approach that al-lows physicians to take into account theirown values, clinical expertise, and patientvalues in addition to published researchfrom level 1 studies.”

At a time when many physicians feeltheir traditional autonomy is rapidly van-ishing, is it surprising that some view itas their right to treat however they seefit, particularly when reinforced daily bydevoted patients who are willing to payout of pocket for their treatment? Thismutually reinforcing alliance of physi-cians and patients has been tremen-dously politically skillful. Their support-ers include numerous politicians whohave even enacted legislation legitimiz-ing their unorthodox treatment and whoinstituted the unprecedented antitrustsuit against the IDSA.

How can we resolve this dilemma?Guidelines adopted by the 8, 000-memberIDSA and the 21,000-member AmericanAcademy of Neurology have only servedto bolster the sense of solidarity in perse-cution of the “Lyme-literate community.”The IDSA agreed to have its guidelines re-reviewed to determine if it will need up-dating. Since the “Lyme-literate physi-cians” all derive substantial income fromtreating patients with “chronic Lyme dis-ease” the overseeing ethicist felt this con-stituted an undue conflict of interest andexcluded them from the new review pan-el. Needless to say, they are already protest-ing that the review will be unfair.

Does this case have implications be-yond Lyme disease? For those physicianswho participate in guideline develop-ment, volunteering innumerable hoursreviewing articles, weighing evidence,debating conclusions while trying to dothis in as fair and rational a way as pos-sible, this movie is like being the guest ofhonor at a Salem witch trial. The intru-sion of this irrational debate into poli-tics—with legislatures and state attor-neys general inserting themselves intothe substance of medical decision mak-ing—could have a profoundly chilling ef-fect on future guideline development.

Equally important, at a time whenAmerican health care is rightly criticizedfor spending too much on tests and treat-ment with limited, if any, impact onhealth outcomes, it is remarkable thatthis “controversy” has resulted in legisla-tures legitimizing treatment that is bothcostly and demonstrably of no meaning-ful benefit. As the United States debateschanges in health care, is this helpful?

This movie makes good theater but itis far removed from reality. Sadly, it servesto perpetuate unfortunate medical carethat subjects patients to unnecessary andsignificant risk, and reflects a process thatis clearly detrimental to the ideal of pro-viding patients with effective, safe, and ap-propriate care. And that is why there is amovie review in WORLD NEUROLOGY. ■

BY JOHN J. HALPERIN, M.D.

Dr. Halperin is the medical director ofthe Atlantic Neuroscience Institute andchair of the department of neurosciencesat the Overlook Hospital, both inSummit, New Jersey, U.S.A., andprofessor of neurology at Mount SinaiSchool of Medicine in New York.

“Phoebe in Wonderland,” written and directed byDaniel Barnz, featuring Elle Fanning, Patricia

Clarkson, and Felicity Huffman

Artistic license, commercial exaggeration, or simple ig-norance in movie scriptwriting

often generate an inaccurate viewof medical conditions. However,sometimes art succeeds wheredocumentaries fail in giving usempathy for disease sufferers.

The movie “Phoebe in Won-derland,” while inaccurate diag-nostically, succeeds in this way.The plot centers around a sensi-tive girl, Phoebe (Fanning), whowishes to land the leading role in the school play, “Al-ice in Wonderland,” and her ensuing struggles with try-

outs, rehearsals, and performance. The idiosyncraticschool drama teacher (Clarkson) recognizes Phoebe’sability to connect with the character of Alice. Unfor-tunately, Phoebe’s traits become magnified as tryoutsand then rehearsals progress, resulting in severe anxi-

ety and compulsions.Ultimately, a psychiatrist

diagnoses her with “Gillesde la Tourette syndrome,”an epiphany for the fami-ly but a surprise to me,since I observed lots of ob-sessive compulsive behav-iors and not tics in thefilm. Still, the film doescapture some essence of

the irrepressible imps in Tourette, a view confirmed tome by several parents of children with the syndrome.

The plot’s juxtaposition of Phoebe’s tensions in bal-ancing external school rules and her internal obsessivecompulsive disorder rules and of Alice’s frustration atWonderland rules works well as a scaffold for the explo-ration of Phoebe’s character and the effects of her symp-toms on her family and classmates. Her situational socialdisinhibition, such as when she spits at a peer or shouts“Fat, you’re fat; you’re fat,” at a stout neighbor, depictsthe impulsiveness and social impairments we see insome children and adults with Tourette. The anguish ofher mother (Huffman) and the stressed parental dialoguearound Phoebe’s symptoms worked particularly well.

So, while the film risks misinforming viewers thatcompulsions equal tics, I recommend suspending yourDSM-IV and enjoying the writing, acting, and cine-matography in “Phoebe in Wonderland.” In theprocess, you gain some insight into the imps in Tourettesyndrome. ■

Artful and Entertaining—Despite the Tic-less Tourette

BY DONALD L. GILBERT, M.D.

Dr. Gilbert is the director ofthe Movement Disordersand Tourette Clinics at theCincinnati Children’sHospital Medical Center inOhio, U.S.A.

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