01 08wfn11 6 - World Neurology · patients were diagnosed with os-teoporosis of the spine based on QCT T scores of less than 3.1 and/or a Z score of less than 1.5. Ten patients had

B Y D E N I S E N A P O L I

Else vier Global Medical Ne ws

Asignificant positive correla-tion exists between bone

fractures and cumulativeantiepileptic drug load amongepilepsy patients with osteo-porosis, independent of the spe-cific drugs used.

And although more research isnecessary, “this finding underlines

the importance of good bonehealth practices in patients withchronic AED use,” Dr. K. Beer-horst and his colleagues reportedin Acta Neurologica Scandinavica(2011 Mar. 21[doi: 10.1111/j.1600-0404.2011.01509.x]).

Dr. Beerhorst, of the depart-ment of neurology at Maas-tricht University Medical Cen-ter, the Netherlands, and hiscolleagues took as their study

cohort all residents of a tertiarylevel “long-stay care facility” forpatients with refractory epilep-sy in that country.

In 2008, they performed adatabase search of the center’saffiliated hospital pharmacy toidentify all adult patients whowere diagnosed with osteo-porosis and treated with a bis-phosphonate at that time.

In most residents, this diagno-

sis was made based on the find-ings of a bone mineral densitystudy with quantitative comput-ed tomography (QCT; n = 32);patients were diagnosed with os-teoporosis of the spine based onQCT T scores of less than 3.1and/or a Z score of less than 1.5.

Ten patients had a dual-ener-gy x-ray absorptiometry (DXA)scan of the lumbar spine andhip to diagnose osteoporosis. In

these patients, “the DXA Tscore threshold defined by the[World Health Organization]was used.”

And in 12 patients, the diag-nosis of osteoporosis (and cor-responding need for bisphos-phonate treatment) was madeon clinical grounds (one or mul-tiple low-energy fractures), plus

B Y A N D R E A PA C E , M D

Earlier this year, the International Fed-eration of Health and Human RightsOrganization (IFHHRO) and the In-

ternational Palliative Care Initiative of theOpen Society Foundations Public HealthProgram, organized a workshop in De Bilt,the Netherlands, on pain treatment as a hu-man right. The participants included painand palliative care specialists and humanrights advocates, and their brief was to re-view a draft resolution on pain as a humanrights issue and to analyze the obstacles togaining access to pain treatment.

The Single Convention of NarcoticDrugs, adopted by United Nations memberstates in 1961, obligated countries to facili-tate access to drugs that could alleviate painand suffering. Yet it is widely acknowledgedthat in both developing and industrial coun-tries, pain remains inadequately treated de-spite the availability of inexpensive and ef-fective pain treatment medications thatcould dramatically improve the quality oflife for patients and their caregivers.

The World Health Organization (WHO)estimates that 5 billion people – about 75%of the global population – live in countrieswhere there is insufficient availability of painmedication. Children and people with intel-lectual disabilities or consciousness impair-

ments are especially at risk for not receivingadequate pain treatment because they oftenare not able to communicate the extent oftheir pain or their need for pain relief.

I attended the workshop as a World Fed-eration of Neurology representative. Myfellow participants and I noted several

barriers to the provision of pain treatmentand palliative care, including: � Failure by governments to enact policieson pain treatment and palliative care;� Failure by governments to provide a func-tioning drug supply system;� Poor training of health care workers; � Lack of information for patients;� Fear among health care workers of legalsanction; and� Unnecessarily expensive pain treatment.

We highlighted the lack of educationamong health professionals for assessingand treating pain and unnecessarily restric-tive government regulations that limit ac-cess to opioid pain medications, such asmorphine, as the major limitations for ad-equate pain treatment and management.

For example, although the WHO has in-cluded morphine (and codeine) on its listof essential medicines, opioids used forpain treatment are still not widely avail-able. “If they are available, there are oftenstrict rules on who can prescribe them,who should administer them, in what doseand with what intervals. As a result, manypeople around the world in need of painrelief unnecessarily suffer from untreatedpain,” the IFHHRO said in a statement af-ter the workshop.

NeurologyWorld

VOL. 26 • NO. 3 • JUNE 2011

Long-term Antiepileptics, Osteoporosis Strongly Associated

Pain Treatment as a Human RightT 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 Antiepileptics • page 4

I N S I D E

See Pain Treatment • page 8

Neurological HistoryStarting in the late 19thcentury, many youngRussian neurologiststrained under Jean-MartinCharcot, whose influencedefined the direction ofneurology in Russia formany years. PA G E 4

East AfricaWe report on two studieswith a regional focus –one on malaria-relatedseizures in Kenya, theother on Parkinson’sdisease in Tanzania. PA G E 6

United StatesThe American Academyof Neurology haspublished the first of itsquality measurements,beginning with measuresfor Parkinson’s diseaseand epilepsy.PA G E 1 0

Regulations limiting access to opioidpain medications can hinder effectivepain treatment, says Dr. Andrea Pace.

CO

UR

TE

SY

DR

. A

DR

EA

PA

CE

WCN 2011 – A Forum for Learning & ExchangeThere’s a rich and varied line-up of content for this year’sScientific Program and daily Teaching Courses, all of thempresented by leaders in their field, and some focusing on theCongress theme, ‘With Africa, For Africa.’See Page 3

01_08wfn11_6.qxp 6/3/2011 4:14 PM Page 1

2 • WORLD NEUROLOGY WWW.WFNEUROLOGY.ORG • JUNE 2011

WORLD FEDERATION OF NEUROLOGYEditor in Chief Dr. Mark Hallett (USA)

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

WFN OFFICERSPresident: Dr. Vladimir Hachinski (Canada)First Vice-President: Prof. Werner Hacke (Germany)Secretary-Treasurer General: Dr. Raad Shakir (United Kingdom)

ELECTED TRUSTEESDr. Wolfgang Grisold (Austria); Dr. Ryuji Kaji (Japan); Dr. GustavoRoman (USA)

CO-OPTED TRUSTEESDonna Bergen (USA); Stephen Sergay (USA)

REGIONAL DIRECTORSDr. Ahmed Khalifa (Pan Arab); Dr. Bruce Sigsbee (North America);Prof. Richard Hughes (Europe); Dr. Alfred K. Njamnshi (PanAfrica); Dr. Ana Mercedes Robles de Hernandez (Latin America);Dr. Ching-Piao Tsai (Asia-Oceania)

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 (USA)

WORLDNEUROLO GY

GLOBAL MEDICAL RESEARCHPublisher Peter F. Bakker,

ELSEVIER GLOBAL MEDICAL NEWSA Division of International Medical News Group

President IMNG Alan J. ImhoffEditor in Chief Mary Jo M. DalesExecutive Editors Denise Fulton, Kathy ScarbeckManaging Editor Renée MatthewsClinical News Editor Jeff EvansAudience Development Manager Barbara CavallaroExecutive Director, Operations Jim ChiccaDirector, Production and Manufacturing Yvonne Evans StrussProduction Manager Judi ShefferCreative Director Louise A. Koenig

EDITORIAL OFFICE5635 Fishers Lane, Suite 6000Rockville, MD 20852+1-240-221-4500 Fax: +1-240-221-2541

US ADVERTISINGAaron Wattenberg

60 Columbia Rd., Building BMorristown, NJ 07960+1-973-290-8212 Fax: [email protected]

Classified Sales Manager, IMNGRobert Zwick+1-973-290-8250 Fax: [email protected] Sales RepresentativeAndrea LaMonica800-381-0569, Fax: [email protected]

INTERNATIONAL ADVERTISINGChris Woods32 Jamestown RoadCamden London NW1 7BY+44 207424 4454 [email protected]

WORLD NEUROLOGY, an official publication of the World Federationof Neurology, provides reports from the leadership of the WFN, itsmember societies, neurologists around the globe, and news fromthe cutting edge of clinical neurology. Content for WORLD NEUROLOGY

is provided by the World Federation of Neurology and Elsevier GlobalMedical News.

Disclaimer: The ideas and opinions expressed in WORLD NEUROLOGY

do not necessarily reflect those of the World Federation of Neurol-ogy or the publisher. The World Federation of Neurology and Else-vier Inc., will not assume responsibility for damages, loss, or claimsof any kind arising from or related to the information contained inthis publication, including any claims related to the products, drugs,or services mentioned herein.

Editorial Correspondence: Send editorial correspondence toWORLD NEUROLOGY, 5635 Fishers Lane, Suite 6000, Rockville, MD 20852, U.S.A.; [email protected];Phone +1-800-798-1822

Address Change: Fax change of address to +1-973-290-8245

POSTMASTER: Send change of address (with old mailing label)to WORLD NEUROLOGY, Circulation, 60 B, Columbia Rd., 2nd Fl.,Morristown, NJ USA 07960

WORLD NEUROLOGY, ISSN: 0899-9465, is published bimonthly byElsevier Inc., 60 B, Columbia Rd., 2nd Fl., Morristown NJ 07960.Phone +1-973-290-8200; Fax: +1-973-290-8250.

©Copyright 2011, by the World Federation of Neurology

EDITOR IN CHIEF’S COLUMN

Doing Our BestWe went into medicine to help people

and we want (or should want) to dothe very best for each person we see.

The field of medicine is complex, however.Not only are there many diseases and manypossible therapeutic choices for them, butchange, in the form of advances or revisionsof old ways, is ever present. Moreover, manyissues are not clear, giving rise to uncertaintyin decision making. Medicine is anart as well as a science. Not onlydo we need a good education atthe outset, but we need to keeplearning as long as we practice.Some of us are self-motivated inthis regard, but it certainly helps tohave regulation to push us, since itis easy to fall into old habits, andthere are plenty of ways to spendour time. Studying can be a bitboring, but there is not going tobe much choice in this regard.

In the United States, the first type of regu-latory learning we were presented with wasthe requirement for continuing medical edu-cation. This is certainly necessary, but difficultto police. Do people really spend the time theysay they do on the courses? Do they reallylearn anything from the experience? Add-onsto this activity have been post tests, compar-isons of pre tests with post tests, question-naires inquiring what you might change inyour practice, and questionnaires after a lapseof time asking what you did change.

Then there is the recertification examina-tion, which leads to maintenance of certifi-cation, or MOC. Periodically, say every 10years, your knowledge and skills are retested.As they say, the value is not in the exam itself,but in the need to study for it! This is be-

coming more popular, and relicensure maysoon require this step.

The most recent trend is evaluation of per-formance in practice, PIP. With this, your ac-tual practice and your medical records are re-viewed and compared with standardguidelines. If your practice does not fit theguidelines, then you are advised on whatchanges you need to make, and there is a fol-

low-up after a given period togauge if there has been improve-ment. This is now starting to beimplemented in the United States,and will be required for the re-newal of board certification inneurology. But how are the bestguidelines determined? Evidence-based medicine has been thetrend, but there have been vitriolicattacks against this approach. Cer-tainly, double-blind, placebo-con-trolled trials are needed, but it is

not always clear how to apply this informa-tion into everyday practice. Now comes qual-ity measures, as described on page 10 by Dr.Christopher Bever and his colleagues on theAmerican Academy of Neurology’s QualityMeasures and Reporting Subcommittee.These are expert, opinion-based guidelinesfor practice. They can help with developingPIP programs and may even produce moreincome for neurologists who follow themthrough pay-for-performance programs. Onehopes that there still will be room for physi-cian judgment, which is certainly necessarysince each patient is different.

Times are changing with more regulation,but it is likely that if you want to do your bestfor each patient, these programs should behelpful. ■

BY MARK HALLETT, MD

WCN 2011 – AN INVITATION

Marrakesh, Where Art,Culture, and Cuisine MingleSir Winston Churchill was par-

ticularly taken by Marrakesh... “Here, surrounded by its exten-sive palm-groves that have sprungout of the desert, the traveler mayrest assured that he will never tireof the majestic view of the snow-covered Atlas Mountains,” hewrote. There’s no doubt that it isan alluring city, and a perfect venuefor 20th World Congress of Neu-rology, Nov. 12 to 17.

The speakers at this year’s con-gress have been selected for their ex-pertise and ability to convey the lat-est information about advances intheir subspecialities to their fellowneurologists (see p. 3). This year’sScientific Program builds on thesuccessful 2009 Bangkok Congress

and includes additional regional andcontinental dimensions, since this isthe first WNC held in Africa.

There has been some concernabout the recent unrest in Africa.Morocco is a stable monarchy thatcontinues to be a popular touristdestination. No travel advisorieshave been issued and plans are go-ing ahead as scheduled. Membersof the Congress Supervisory Com-mittee will be visiting Marrakeshthis summer, so we will have up-to-date, “on-the-ground” informa-tion about the city.

Come to Marrakesh and be partof a milestone scientific and cul-tural event!

Vladimir Hachinski, MDPresident, WFN

Some call Marrakesh “the oriental gateway to the Atlas Mountains,”seen here as a striking backdrop to a cluster of palm trees.

©F

RA

NÇ

OIS

EB

RO

/IST

OC

KP

HO

TO

.CO

M

01_08wfn11_6.qxp 6/3/2011 4:15 PM Page 2

JUNE 2011 • WWW.WFNEUROLOGY.ORG WORLD NEUROLOGY • 3

PRESIDENT’S COLUMN

Putting Brain Health on the Global Disease GridThe global disease burden generated by noncom-

municable diseases (NCDs) is substantial, par-ticularly in low- and middle-income countries,

and the associated deaths are on the rise, according toa recent report by the United Nations. In an effort toraise awareness of these diseases, the or-ganization plans to hold a summit meetingon NCDs in New York, Sept. 19-20, 2011,to address the effects of these diseases anddraw up a plan of action to reduce theirprevalence.

The four groups of diseases that the UNhas deemed account for most NCD deathsare: cerebrovascular disease, diabetes, can-cer, and pulmonary disease. These diseasesshare risk factors, and their incidence couldbe substantially reduced if there were aconcerted effort to control tobacco use;lower salt intake, and consumption ofsweetened drinks, saturated, and trans fats; and to en-courage increased physical activity.

It is worth noting, however, that the brain and braindisease are not on this agenda, except by implication:“cerebrovascular disease” includes stroke.

In an attempt to have the brain – and by extension,neurology care – included on the UN agenda, the

World Federation of Neurology invited rep-resentatives from the European Brain Coun-cil, the International Brain Research Orga-nization, the International Child NeurologyAssociation, the World Federation fromNeuroRehabilitation, World Federation ofNeurosurgical Societies, the World Psychi-atric Association (WPA) to meet with a rep-resentative from the World Health Organi-zation in Geneva in March. The WorldHeart Federation, at our invitation, sent anobserver. (Since the March meeting, theWorld Stroke Organization, Alzheimer’sDisease International, and the Internation-

al League Against Epilepsy have joined the Alliance.)At that meeting, we formed a working group of the

World Brain Alliance, of which I am chair, and we draft-ed a document titled “The Brain: A Key in the FightAgainst Noncommunicable Diseases” to argue ourcase for inclusion.

In April, I attended the first Global Ministerial Con-ference on Healthy Lifestyles and NoncommunicableDisease in Moscow, along with Bo Norrving, presidentof the World Stroke Organization and Marc Fisher, ed-itor of the journal Stroke and the official delegate of theAmerican Heart Association. This time, our missionwas to try to get “cardiovascular disease” spelled outas “heart disease and stroke.” The brain is still not partof the global health agenda, but the draft document ofthe World Brain Alliance was circulated to all the par-ticipants at the Moscow meeting. I shall follow up withyou on the outcome.

No one can tell how far our efforts will take us, butthe fact that all brain organizations we invited are will-ing to join us in the World Brain Alliance, gives us hopethat we can do much to ensure healthier brains for ahealthier world. ■

BY VLADIMIRHACHINSKI, MD

WORLD CONGRESS OF NEUROLOGY 2011

Hands-On Teaching Courses, Rich Scientific ProgramParticipants at this year’s World Con-

gress of Neurology from Nov. 12 to17 in Marrakesh, Morocco, will have ac-cess to a multitude of hands-on teachingcourses, all of them taught by leadingworld experts in each field.

“The [Marrakesh] congress presentsan exceptional opportunity for partici-pants to meet their colleagues fromaround the world and to learn abouttopics of international importance andconcern,” said Dr. Wolfgang Grisold,chairman of the World Federation ofNeurology (WFN) Teaching CourseCommittee.

“The teaching courses, especially,will provide forums for learningand exchange among all partic-ipants – those who are startingout in their careers as well asmore senior, practicing neu-rologists,” he continued.

Clinical and General ContentThe courses will runthroughout each day of thecongress in parallel to therich and varied scientific pro-gram. Participation in acourse will translate intoseparate CME credits, inaddition to the CME credits givenfor participation in regular congresssessions.

With a selection of 49 teaching cours-es and six workshops offered at thisyear’s congress, the course content cov-er a range of clinical and more generaltopics.

The clinical subject matter will in-clude epilepsy, stroke, infection, sleep,pain, child neurology, movement dis-orders, and dementia, among others.

These sessions will feature practicaldemonstrations, using equipment spe-cific to the condition or disease underdiscussion, as well as live demonstra-tions on patients.

Advocacy, Education, How-To AdviceThere will also be sessions addressingeducational topics, for example, thePalatucci Advocacy Leadership Forummeeting with the American Academyof Neurology and neurological educa-tion sessions.

In addition, the International Work-ing Group of Young Neurologists and

Trainees workshop for young neu-rologists. Practical aspects such

as how to deal with good andbad news, and how to write apaper will be other importanttopics.

Teaching courses will alsofocus on challenges facingneurologists in low-incomecountries, such as one titledDementia in the DevelopingWorld.

For the first time, theWFN will offer a freeteaching course everyday, dedicated to resi-

dents and young neurologists and cov-ering topics such as disturbed con-sciousness, tremor, diplopia, andmyopathy. Experts will give insight intothese important and vital aspects ofclinical neurology, and this will be a fu-ture key element of teaching courses.

The World Stroke Organization willoffer ABC Cardinal Principles of StrokeManagement, following the trend to of-fer broad access to neurological devel-opment in teaching courses.

The choice of subject matter reflectsthe emergence of new therapies and di-agnostic technology, such as Botox,deep-brain stimulation, EEG video, in-terventional radiology, and neu-roimaging, as well as the more refineddistinctions between the subspecialties,such as sports medicine, brain injury,neurorehabilitation, and neurocriticalcare.

The congress secretariat will publish afull syllabus for each course ahead of thecongress starting date.

Scientific ProgramThe scientific program will feature animpressive line-up of international ex-perts, from Africa and around theworld. The bulk of the program will bemade up of main topic sessions, eachwith a number of lectures under a com-mon theme.

Many of the sessions and lectureswill focus on the congress theme,“With Africa, for Africa,” and will high-light the achievements of African neu-rologists and the challenges they face indelivering neurological care. These in-clude “History of Neuroscience in theMaghreb” on Monday, Nov. 14, and“Neurological Care Policy in Africa” onWednesday, Nov. 16.

Daily plenary sessions will include thefollowing topics:� The Mirror Neurons and the Cogni-tive Brain (Giacomo Rizzolatti, Italy);� The Future of DBS in Neurology andPsychiatry (Alim L. Benabid, France);� Challenges in Adopting InternationalGuidelines Into National Stroke Pro-grams (Lu Chuanzhenn, China);� Neuroaesthetics: Artistic Creativityand the Brain (Sémir Zeki, UK); and

� Vertigo and Balance (David Zee, USA). Also included under the plenary ses-

sions are the Named Orations:� The Melvin D. Yahr Lecture (present-ed by Anthony Lang, Canada);� The Neurology of HIV – the Eddieand Piloo Bharucha Lecture (Elly Katabi-ra, Uganda);� Soriano Lecture (Christian Elger, Ger-many); and� Motor Neuron – the Fulton Sympo-sium Soriano Lecture (Hidehiro Mizu-sawa, Japan).

Choices for the Presidential SessionThe topics for the presidential sessionwill be:� Neuropsychology of the Arabic Lan-guage, which will be presented by ElMostafa El Alaoui Faris, Morocco, whois the president of the WCN 2011;� Hypertension and the Brain (Vladi-mir Hachinski, president of the WFN);and� The Changing Spectrum of Neurolo-gy: New Agenda, Opportunities, and Al-lies (Werner Hacke, Germany).

In addition to the aforementioned ses-sions, attendees will also be able to par-ticipate in regional and educational ses-sions and daily debates.

For More Information…� Abstract submission. The closingdate for the submission of abstracts isJune 15, 2011. Submit your abstract atwww2. kenes.com/wcn/scientific/Pages/Call.aspx.� Scientific program. See ww2.kenes.com/wcn/scientific/Pages/Interac-tive_Scientific_Program.aspx.� WCN 2011 homepage. See www.wcn-neurology.com. ■

01_08wfn11_6.qxp 6/3/2011 4:16 PM Page 3


signs of osteoporosis seen on conven-tional x-rays.

Overall, this search yielded 54 patients,out of a total 261 residents at the center(21%), who were diagnosed with osteo-porosis and were being treated with abiphosphonate; 33 patients were male,and the mean age was 58.2 years. Themean duration of disease was 53.7 years.

All but 3 of the 54 patients studiedwere taking one or more of the so-called“enzyme-inducing” antiepileptic drugs(AEDs), which the authors stated areknown to be associated with negative ef-fects on bone mineral metabolism andbone quality.

The most common of these in the pre-sent study were carbamazepine (39 pa-tients, or 67%), lamotrigine (21 patients,or 39%), and phenytoin (15 patients, or28%).

Only three patients did not use en-zyme-inducing AEDs; two of these re-ceived no AEDs at all, and a third re-ceived monotherapy with valproic acid.

To gauge drug therapy, the authorscalculated each patient’s “cumulativedrug load,” that is, their total duration ofepilepsy diagnosis multiplied by the cur-rent number of AEDs.

“This surrogate measure of cumula-tive antiepileptic drug load was used be-cause no standard measure for chronictreatment with multiple drugs duringmany years is available,” they wrote.

The mean number of previous frac-tures among the cohort was 4.7, with arange between 0 and 18.

The authors also assessed ambulatorystatus among the study participants,which ranged from bedridden status in14 patients, to wheelchair-bound in 8 pa-tients, to being able to walk with an aidin 10 patients, to unassisted ambulationin the remaining 22 patients.

Overall, using the Pearson correlationcoefficient, the authors found that thenumber of fractures correlated signifi-cantly with ambulatory status (r = –0.269;P = .05), cumulative drug load (r = 0.286;

P = .04), and current number of AEDs (r = 0.283; P = .04).

They found a negative correlation be-tween the cumulative drug load and theT score by QCT (r = –0.456; P = .04),with a determination coefficient of 0.137.

“Correlations could not be providedfor individual drugs in our population, asonly a minority was on monotherapyand even less patients had always beenon monotherapy of the same antiepilep-tic drug,” wrote the authors.

The authors also undertook a linearregression analysis, looking at durationof epilepsy, cumulative drug load, age,body mass index, ambulatory status, al-cohol consumption, caffeine intake, andsmoking as possible predictors of frac-tures.

They found that among these, onlydrug load was independently significant(P = .029).

“This does not provide concluding ev-idence for a causal relationship, but is atleast ‘a smoking gun’ illustrating a strongassociation between ‘chronic,’ that is,long-term treatment with multiple AEDs,and osteoporosis,” wrote the authors.

The authors conceded several limita-

tions of this study. For one, they point-ed out that many of the residents of thelong-term care facility they studied hadmild to moderate intellectual disability.

Indeed, “People with an intellectualdisability are reported to have high ratesof osteoporosis and osteopenia, possiblyas an effect of reduced mobility,” theywrote. “However, when entering mo-bility into the linear regression analysis,the association between drug load andfractures was preserved, suggesting againthe independent effect of cumulativedrug load.”

The authors also stated that the cur-rent gold standard for bone mineral den-sity measurement is the DXA scan, andideally, all patients would have been mea-sured against that technique.

“However, we were dependent on thecounty hospital where our residentswere sent to for their bone mineral stud-ies,” they wrote. “In this hospital, DXAscan has become more available in thelast 10 years, whereas most of our pa-tients were examined earlier.”

Disclosures: The authors declared noconflicts of interest relating to this study,and no funding source. ■

Good Bone Health Care NeededAntiepileptics • from page 1

FROM THE WFN RESEARCH GROUP ON THE HISTORY OF THE NEUROSCIENCES

How Charcot’s Influence Defined Russian NeurologyBy the middle of the 19th century, there were no

formally trained neurologists in Russia, eventhough courses on nervous and mental disorders

had been offered at Moscow Uni-versity since 1768. This situationmade training abroad an absolutenecessity, and Germany, England,and France were the destinationsof choice given their prominencein medical science at the time.

Russians were no strangers toFrance, and Paris, in particular,given that many considered trav-eling to France a form of culturaland intellectual apprenticeship. Likewise, for youngRussian doctors interested in nervous and mental dis-eases, going to Paris was a natural choice and automat-ically meant going to Jean-Martin Charcot (1825-1893),who was in the avant-garde of French clinical neurolo-gy and based at the Salpêtrière Hôpital. Charcot was adevoted teacher whose extraordinary skills attracted ahuge number of pupils from abroad. But he was also in-terested in receiving foreign students and chairing theirtheses as part of his longer-term plan to secure the chairof neurology in the faculty of medicine and promote hisaccession to the Académie des Sciences et de Médecine.

Aleksei Yakovlevich Kozhevnikov (1836-1902), the pi-oneer of Russian neurology, was one of the first Russiansto visit the Salpêtrière, where he studied under Charcotfrom 1867 to 1868 after graduating from Moscow Uni-versity and training in Germany and England. The timehe spent with Charcot strengthened his belief that neu-rology should be seen as an independent discipline.

When Kozhevnikov returned to Russia in 1869, thecouncil of Moscow University chose him to lead the de-partment of nervous and mental diseases, making himthe first Russian professor of neuropathology – lapathologie nerveuse – his preferred term for the disciplineand one that would be used in Russia and the SovietUnion for many decades thereafter. It was not until1882, 13 years later, that Charcot was appointed chairof the study of diseases of the nervous system in Paris.

Kozhevnikov was a faithful follower of Charcot’sanatomoclinical approach. As the head of the departmentin Moscow, he insisted on his young colleagues and stu-

dents going to study inParis, setting up a steadyflow (until the RussianRevolution of 1917) ofyoung Russian doctorspursuing their studies atthe Salpêtrière. Amongthose who went to Parisand who would later helpchart the course of Russ-ian neurology (and psychi-

atry), were Sergey Sergeevich Korsakov (1854-1900),Vladimir Karlovich Roth (1848-1916),Lazar Salomowitch Minor (1855-1942), and Liverij Osipovich Darkshe-vich (1858-1925).

Students from St. Petersburg alsosought training in Paris. IvanPavlovich Merzheevskii (1838-1908)was one of the first St. Petersburgpsychiatrists to train in Paris. Beinginterested in neurology and psychia-try, he worked both with Charcotand psychiatrist Valentin Magnan(1835-1916). Merzheevskii’s mostoutstanding pupil was VladimirMikhailovich Bekhterev (1857-1927).Bekhterev arrived in Paris in 1883,where he worked with Charcot andthe psychologist Pierre Janet (1859-1947). He became very interested inhypnosis and spent many hours withCharcot during hypnotic sessions.This very fact would leave its imprint on the differencesbetween the Moscow and St. Petersburg schools of neu-rology and psychiatry. In Moscow, Kozhevnikov hadsought the separation of neurology and psychiatry,whereas in St. Petersburg, Bekhterev created a multi-disciplinary approach, in which he sought to combine

neurology, neurophysiology, psychiatry, psychology,and neurosurgery. He succeeded in implementing thisapproach by founding the Psychoneurological Institutein St. Petersburg in 1907, where he remained as direc-tor until his untimely death in 1927.

Charcot and his school did not just offer profession-al training but also created the best minds, which woulddefine the direction of neurology in Russia for manydecades. After returning home, Russian doctors pro-ceeded to make their own original contributions. Re-markably, though trained by the same teachers, each ofthese future “founders of neurological and psychiatricschools” followed his individual path, which resulted inan undeniable diversity in Russian neurology and psy-chiatry during the period of their formation. (For more

information, see Eur. Neurol. 2011;65:75-81.) ■

PETER J. KOEHLER, MD, PHD, is the editor of thiscolumn. Dr. Koehler is a neurologist in the department ofneurology at the Atrium Medical Centre, Heerlen, theNetherlands. Visit his website at www.neurohistory.nl.

BY ALLA VEIN, MD, PHD

Dr. Vein is a neurologist atthe neurology department ofLeiden University MedicalCentre, the Netherlands, anda member of the WFN Re-search Group on the Historyof the Neurosciences.

Charcot and his daughter Jeanne (seated center) in Moscow in 1891,with Kozhevnikov (right front). Standing (from left) are Muratov,Rossolimo, Jean Charcot, Pribytkov, Roth, and Minor.

CO

UR

TE

SY

DR

. A

LL

AV

EIN

01_08wfn11_6.qxp 6/3/2011 4:17 PM Page 4

Fourth Congress of the Pan-Asian Committee for

Sun 28 to Tue 30 August 2011, Raffles City Convention Centre, SingaporePlatinum Sponsor Gold Sponsors Bronze Sponsor Media Partners




The benefits – and possible con-traindications – to the use of statinsin Alzheimer’s disease remain poor-

ly understood, and their widespread usein that population is premature, accord-ing to a review.

“Although the evidence provided withpreclinical data substantiated the potential

beneficial effects of statins in dementiaand AD, the results provided by epidemi-ological studies and [randomized con-trolled trials] are quite contradictory,”wrote Dr. D. Allen Butterfield and his col-leagues (Pharmacological Research 2011April 21 [doi: 10.1016/j.phrs.2011.04.007]).

“However, strong consideration forresearchers and clinicians in the near fu-ture to investigate whether or not statintherapy should be restricted to selectedpopulations of demented individualswith the best chance of efficacy derivedfrom evidence-based medicine is recom-mended,” he added.

According to Dr. Butterfield, of the Uni-versity of Kentucky, in Lexington, USA, de-spite their well-known beneficial effects onhyperlipidemia, statins’ pleiotropic effectson other pathways can be both therapeu-tic as well as detrimental.

For example, the inhibition of HMG-CoA reductase – statins’ main mecha-nism of action – also reduces the pro-duction of coenzyme Q10, an antioxidantnecessary for energy metabolism in theheart, skeletal muscle and liver, anddolichol, which may function as a “radi-cal scavenger,” said Dr. Butterfield.

Statins, which were at one time pro-posed as a possible treatment for multi-ple sclerosis, also affect myelination. A2010 study found simvastatin had a detri-mental effect on oligodendrocyte out-growth, “a key step in the remyelinationprocess,” wrote the researchers ( J. Neu-rosci. Res. 2010;88:3361-75).

Nevertheless, at the preclinical level,several studies have shown promise. In a2009 study, researchers reported thatatorvastatin reduced amyloid beta-in-duced oxidative stress – “strongly asso-ciated with amnestic mild cognitive im-pairment] and AD” – in mice models(Neurobiol. Dis. 2009;35:406-14).

Another small study in humansshowed a reduction in tau protein phos-phorylation, measured in cerebrospinalfluid, after 14 weeks of treatment with

Review Suggests Caution in UsingStatins for Treating Alzheimer’s

simvastatin – but not pravastatin ( J.Alzheimers Dis. 2006;10:399-406).

On the other hand, clinical randomizedcontrolled trials have mostly confirmedstatins’ null or negative effects on cogni-tion, according to the current review.

Dr. Butterfield cited the large PROS-PER study, which followed about 6,000adults aged 70-82 years who were treat-ed with either a daily dose of pravastatinor placebo for a mean of 3 years. The tri-

al showed no significantdifference in cognitive de-cline between groups ( J.Neurol. 2010;257:85-90).

A similar conclusionwas reached in theLEADe study (Lipitor’sEffect in Alzheimer’s De-mentia), in which 640adults with mild to mod-erate AD were random-ized to atorvastatin 80mg/day or placebo for 72weeks.

That study found no differences be-tween the treatment and placebo groups,either on cognition (as measured byAlzheimer’s Disease Assessment Scale-Cognitive Subscale, P = .26) or globalfunction (as measured by Alzheimer’s Dis-ease Cooperative Study Clinical GlobalImpression of Change, P = .73) comparedwith placebo (Neurology 2010;74:956-64).

Why such a discrepancy between find-ings? One reason may be baseline serumcholesterol levels. “Recalling that cho-lesterol is a main component of cellmembranes, in particular myelin, if cho-lesterol blood levels fall due to uncon-trolled therapy with lipid loweringagents, nervous function would also de-crease,” wrote the authors.

However, while they cautioned against

administering statin therapy toAlzheimer’s patients with low choles-terol plasma levels, “such as those affect-ed by liver failure,” they conceded that atleast one study has shown only slight re-duction in cerebrospinal fluid cholesterollevels after 6-7 months of simvastatin oratorvastatin therapy, with a return tobaseline levels after 3 years (Dement.Geriatr. Cogn. Disord. 2009;27:519-24).

“This finding lends support to the ideathat, despite the changes in plasma cho-lesterol levels, only minimal changes inbrain cholesterol occur after statin ther-apy and, therefore, the effect on cognitivefunctions are independent of the ‘local’cholesterol metabolism,” they wrote.

Another possible factor causing thevarying degrees of statin efficacy found inthe literature is concomitant medicationusage, which is highly prevalent in the el-derly population targeted in these studies.“All statins, with the exception of pravas-tatin, are metabolized by CYP3A4 orCYP2C9, and their plasma levels could bereduced or increased in the case of con-comitant administration of drugs that in-duce or inhibit these CYP isoforms,”wrote the researchers.

Based on these inconsistent findings,they recommended several future avenuesfor research into the relationship betweenstatin therapy and Alzheimer’s. For one,they advocated for selective trials of pa-tients aged 65-75 years, “the age whichseems to receive more benefit from statintherapy,” compared with older patients.

“Another recommendation to consid-er is to study in-depth the effect of statinsin individuals with mild cognitive im-pairment, in order to understandwhether or not the antioxidant effect ofthese drugs could block or slow the tran-sition phase to AD,” they added. ■

Major Finding: Statin therapy in Alzheimer’s dis-ease shows conflicting outcomes, both in pre-clinical data and randomized controlled trials.

Data Source: A perspective on the current litera-ture on statin therapy in Alzheimer’s disease anddementia.

Disclosures: Dr. Butterfield disclosed that the re-view was partially funded by a grant to Dr. But-terfield from the U.S. National Institutes ofHealth. The authors made no other disclosuresin relation to this study.

VIT

AL

S

WFN 2011TRUSTEE ELECTION

NominationsDue by Oct.14In accordance with the Memoran-

dum and Articles of Association ofthe World Federation of Neurology(WFN), the election of one newTrustee will take place at the annualgeneral meeting of the Council of Del-egates during the World Congress ofNeurology in Marrakesh in November.

The present holder of the post, Dr.Gustavo C. Romano, as is his right, isstanding for re-election, and membersocieties have been given the oppor-tunity to propose candidates to theNominating Committee. The com-mittee has drawn up the following listfor presentation to the Council:

� Dr. Gustavo C. Roman, USA� Prof. John Wokke, the Nether-lands

It remains open to any five or moreauthorized WFN Delegates to joint-ly submit the name of any other can-didate to the Secretary-TreasurerGeneral up to 30 days before the dateof the Council of Delegates’ AGM,that is, Oct. 14, 2011. Any nominationreceived after this date unfortunatelycannot be accepted.

The nominations can be sent toDr. Raad Shakir, Secretary-Treasur-er General, World Federation ofNeurology, Hill House, HeronSquare, Richmond, Surrey, TW91EP, UK. They can also be faxed toDr. Shakir at 44 (0) 208 439 9499 ore-mailed for his attention to [email protected]. ■

01_08wfn11_6.qxp 6/3/2011 4:18 PM Page 5


REGIONAL FOCUS – EAST AFRICA

Study Explores Effects of Parkinson’s in Rural TanzaniaB Y J E F F R E Y S. E I S E N B E R G


Parkinson’s disease has physical, psychological, so-cial, and economic consequences for patients andcaregivers in rural Africa, where misconceptions

about the cause, symptoms, and appropriated treat-ment abound, according to a new study in BMC PublicHealth.

An estimated 10 to 405 per 100,000 people worldwidehave Parkinson’s disease. In rural northern Tanzania,32 of about 161,000 people living in the area studiedhave Parkinson’s. However, the researchers wrote,there appears to be no published social science studiesof Parkinson’s disease in Africa.

So, Gerry Mshana, PhD, of Tanzania’s National In-stitute for Medical Research in Dar es Salaam, and col-leagues sought to investigate the experiences of patientswith Parkinson’s disease and their caregivers.

The study took place within the Hai district in Tan-zania, where researchers conducted 62 semi-structuredinterviews among 28 Parkinson’s sufferers, 28 caregivers(1 for each patient), 4 health-care workers, and 2 tradi-tional healers (BMC Public Health 2011;11:219). The pa-tients ranged in age from 45 to 94 years, with 26 (93%)past age 64. Most of the caregivers were women andwere mainly the wives, daughters, or daughters-in-lawof the patients. The researchers also conducted six fo-cus group discussions in three villages among peoplefrom various socioeconomic backgrounds.

Patients and caregivers alike reported how Parkin-son’s disease had changed their lives for the worse,including: � Physical symptoms and disabilities. These were themost prominent effect of the illness among patients. Ofthe 28 patients interviewed, 18 said they could nolonger dress themselves, 21 said they could not walkwithout assistance, 20 said they could not eat proper-ly, and 5 said they could not turn in bed. Also, four malepatients said the disease led to erectile dysfunction, andtwo reported constant fatigue.� Economic losses. Twenty-three of the 28 patients in-terviewed said they were unable to work, leading to re-

duced income and greater dependency on siblings andother relatives. Most caregivers also reported econom-ic losses, as their caregiving roles prevented them fromearning an income.� Sense of hopelessness and social isolation. Five pa-tients said they experienced PD-related stigma fromfamily and community members. Also, four patients de-scribed themselves as extremely bitter and their lives ashopeless.

There were similar effects oncaregivers, who said they felt bothhumiliated by becoming more de-pendent on relatives and helplessbecause they did not know whatParkinson’s disease was and howto help their loved ones. They alsofelt helpless when they took pa-tients to the hospital and had notseen any improvement in theircondition.

As with patients, many caregivers said they did nottake part in social activities. “Reports of [caregivers] fail-ing to engage in social activities such as funerals and fes-tivals highlight the serious social consequences as a re-sult of their caring responsibilities,” the researchersreported. “This further demonstrates that the conse-quences of PD extend beyond the sufferers, especiallyin this context where help from health professionals suchas community nurses may not be readily available.”

Awareness of the disease and its implications wasvery low among residents of Hai, the study found. Fewpeople said they have heard of the disease, and eventhose who have heard of Parkinson’s disease had mis-conceptions about the specific causes. For example,some thought it was caused by cold weather, hyper-tension, stress, poisoning, use of insecticides, having sexwhile menstruating, or eating certain foods duringpregnancy. These misunderstandings were widespreadamong different groups of people.

“Despite the outlined misconceptions, some re-spondents had correct notions about PD, such as thatit mainly affects the elderly,” the researchers add. “Af-ter probing, some respondents from all groups

mentioned correct symptoms such as tremor, walkingdifficulties, body pain, and dysphasia.”

These misconceptions, the researchers say, can causepatients to further isolate themselves or not seek ap-propriate treatment. Also, most of the patients were notaware that they had Parkinson’s disease; rather, theysought treatment for specific symptoms.

Patients decided on treatments either on their ownor in collaboration with family members and, in some

instances, with neighbors and fam-ily friends. Affordability, includingthe costs of transportation, con-sultations, and drugs, was theirprimary consideration in treat-ment-seeking decisions.

Only two patients were receiv-ing Western-style treatmentthrough outsourcing drugs fromother regions of the country andoutside of Tanzania, but most pa-

tients received no Western-style treatment. “This may be a manifestation of either lack of prop-

er diagnosis due to the lack of capacity within the healthcare system, or inability of sufferers to ‘outsource’ thedrugs,” the researchers say. “The reported lost oppor-tunity to generate income may make it difficult for suf-ferers and their carers to afford treatment even if it wereavailable within the existing health-care system.”

The researchers are planning follow-up studies thatwill include more longitudinal data. Meanwhile, theysay, this study shows the need for appropriate planningfor PD diagnosis. In poor settings, such as sub-SaharanAfrica, interventions must be cost effective, tailored tothe local population, and include a reliable, affordable,and sustainable supply of PD drugs. Interventions alsomust prioritize the needs of specific groups of care-givers, the researchers said.

“Health policy setting at the national and interna-tional levels needs to recognize that early and appro-priate intervention of the ‘nontraditional’ illnesses in de-veloping countries, such as PD, may offer a betterchance of success,” wrote the authors, who had nocompeting interests to disclose. ■

B Y J E F F R E Y S. E I S E N B E R G


The incidence of malaria-associatedseizures in children in sub-Saharan

Africa decreased during a 7-year observa-tion period, coinciding with a decrease inmalaria itself, according to a study in Brain.This was similar to a decline the re-searchers predicted at the outset, and theybelieve it could lead to a reduced incidenceof neurological disabilities and epilepsy as-sociated with malaria in this area.

Malaria caused by Plasmodium falci-parum is the most common cause ofacute symptomatic seizures in childrenadmitted with parasitaemia to a ruralhospital in a part of Kenya in whichmalaria is endemic.

The risk for seizures, however, de-creases with age. Also, malaria trans-mission and admissions on the Kenyancoast have been significantly lower dur-ing the past decade, possibly due to morecontrol interventions, effective anti-

malarial drugs and improved education.Symon M. Karluki, assistant researcher

at Kenya Medical Research Institute inNairobi and his team believed the coin-cidence of a decrease in admissions with

acute symptomatic seizures and a declinein malaria transmission could help themdetermine an appropriate measure ofseizures that are attributable to malaria.

“We also hypothesized that most ofthe decrease in acute symptomatic

seizures would occur in admissions witha positive blood-slide for malaria ormalaria-associated seizures (MAS) com-pared with admissions with a negativeblood-slide for malaria or non–malaria-

associated seizures (non-MAS),” the researchers said.

Using an online admissionsdatabase, the researchersidentified all children frombirth to age 13 who were ad-mitted to Kilifi District Hos-pital between 2002 and 2008with a history of seizures andreviewed their clinical notesfor information on malariastatus and seizures (Brain2011 April 10 [doi:10.1093/brain/awr051]).

The medical history included theparental description of episodes ofseizures, number and duration ofseizures. Lab work upon admission in-cluded full blood count, malaria para-sitaemia, plasma glucose, venous blood

gases, and blood culture were done on allchildren at admission, including the com-parison group. Also, the nursing staffrecorded the time of onset and cessationof seizures, what antiepileptic drugswere administered, and the level of con-sciousness at the end of a seizure, as de-termined by the Blantyre Coma Score.

The researchers used logistic regressionto determine the proportion of seizuresthat were due to malaria and then to de-termine if the observed decrease in acutesymptomatic seizures was a measure ofseizures that are attributable to malaria.

A total of 34,057 children ages 0-13were admitted during the study period.Upon admission, 7,150 children (21%)had P. falciparum, and 5,580 (16%) had ahistory of seizures, the researchers found.

Further analysis showed that 4,370(61.1%) children admitted with malariaparasitaemia did not have a history ofseizures that led to hospitalization. Afterexcluding children who lived outside of

In Kenya, Decline in Malaria Echoed in Dip in Seizures

Major Finding: From 2002 to 2008, all acutesymptomatic seizures decreased by 809/100, 000 a year, with 93.1% of this decreaseoccurring in malaria-associated seizures.

Data Source: Study of children ages 0-13who were hospitalized with a history ofseizures in a rural Kenyan hospital.

Disclosures: The Wellcome Trust, Kenya Med-ical Research Institute, and Biomedical Re-search Centre in Oxford provided funding forthe study.

VIT

AL

S

Continued on following page

PATIENTS AND CAREGIVERSSPOKE OF THEIR ECONOMIC

LOSSES, PARKINSON’S-RELATEDSTIGMA, AND REJECTION BYFAMILY AND COMMUNITY.

01_08wfn11_6.qxp 6/3/2011 4:18 PM Page 6

The Lancet Neurology is the world’s leading journal in clinical neurology.Stay abreast of the latest developments – subscribe today

www.thelancet.com/neurology

THE LANCET® is a registered trademark of Elsevier Properties SA, used under licence.

Where great mindscome together


the study area, the final analysis data setconsisted of 4,573 children.

Malaria parasitaemia was detected in140 (10%) of the 1,411 children in thecomparison group and the prevalence ofparasitaemia decreased consistently be-tween 2002 and 2008, the researchers say.Also, the mean age of admission formalaria-associated seizures appeared toincrease, but that of non–malaria-asso-ciated seizures remained the same.

The overall incidence of acute sympto-matic seizures was 651/100,000 a year. Itwas 400/100,000 a year for acute complexsymptomatic seizures and 163/100,000 ayear for febrile seizures. The adjustedmalaria-attributable fractions for acutesymptomatic seizures in all admissionswith parasitaemia were relatively high anddecreased with age in children older than6 months of age.

From 2002 to 2008, all acute sympto-matic seizures decreased by 809/100 000a year, with 93.1% of this decrease occur-ring in MAS. The decrease in the incidenceof acute complex symptomatic seizuresduring the period was 111/100,000 a year(57.2%) for convulsive status epilepticus,440/100,000 a year (73.7%) for repetitiveseizures and 153/100,000 a year (80.5%)for focal seizures.

The adjusted malaria-attributable frac-tions for seizures with parasitaemia were92.9% for all acute symptomatic seizures,92.9% for convulsive status epilepticus,93.6% for repetitive seizures and 91.8% forfocal seizures. The adjusted malaria-at-tributable fractions for seizures in childrenabove 6 months of age decreased with age.

“The observed decrease in all acutesymptomatic seizures (809/100,000 ayear) was similar to the predicted decline(794/100,000 a year) estimated by malar-ia-attributable seizures was similar tothe predicted decline that was estimatedusing the modeled malaria-attributablefractions for seizures and suggests thatthe decrease observed is an approximatemeasure of the childhood admissionswith seizures that are attributable tomalaria,” the researchers wrote. “Theobserved decrease in seizures could leadto reduced neurological disabilities andepilepsy associated with malaria in thisarea,” they said. ■

Continued from previous page

Advocacy Honor for Michael FinkelDr. Michael Finkel, past-president of

the World Neurology Foundation(WNFo), an independent non-

profit organization that serves as a char-itable arm of the World Federation ofNeurology, has been named the 2011

Kenneth M.Viste, Jr., MD,Patient Advo-cate of the Yearfor his commit-ment to patientadvocacy.

The awardwas establishedin 2007 to recog-nize memberphysicians who,

like Dr. Finkel, demonstrate outstandingcommitment to advocating for the pa-tient community. It is sponsored by theAAN and endowed by gifts from Dr.Viste’s friends and colleagues to the Ken-neth M. Viste, Jr., MD, Leadership Fund.

During his tenure as president of theWNFo from 2006-2011, Dr. Finkel wasthe driving force behind a number of ad-vocacy and teaching projects in variousregions of the world.

Earlier this year, he spearheaded the

Nigeria-Florida Neuroscience Partner-ship between the Florida Society of Neu-rology and the Nigerian Society of Neu-rological Sciences and Nigerian StrokeSociety to develop neurology trainingand services in Nigeria (WORLD NEU-ROLOGY, February 2011, p. 1). At theWorld Neurology Congress in Bangkok,he offered the first session of its kind onadvocacy training for attendees (October2009, p.2).

Dr. Finkel has also been closely involved

with the Tool Kits for Africa project, whichprovides the basic tools for the neurolog-ical exam (April 2009, p. 14), and in 2008,he assisted the organizers of the joint12th Asian Oceanian Congress of Neu-rology and 16th Annual Conference of theIndian Academy of Neurology in NewDelhi in presenting their first advocacyworkshop (December 2008, pp. 1 and 13).

For more information about the pa-tient advocacy award, contact DerekBrandt at [email protected]. ■

DR. MICHAEL FINKEL

01_08wfn11_6.qxp 6/7/2011 12:05 PM Page 7


This failure to treat pain appropriate-ly means that many patients suffer fromacute, chronic, or cancer-related painand are treated with substandard medi-cines or not at all, leading to adverse out-comes, especially high morbidity andmortality, and a lower quality of life forpatients and caregivers. People withchronic pain are affected not only phys-ically (such as reduced mobility), butalso psychologically. Further complicat-ing the treatment of pain is that:� Pain experience and reporting painare strongly influenced by cultural, so-cietal, religious, and other factors; � Pain treatment is frequently not sim-ple – there is a wide gap between knowl-edge and practice;� Health workers often have unfoundedconcerns about opioid tolerance, depen-dence, side effects, and addiction; and� Many believe that opioid doses shouldrelate to disease severity – rather than topain intensity – and that nonopioid drugsshould be used in preference to opioids.

International law obliges countries tomake adequate pain medications avail-able. They have an obligation to imple-ment palliative care services and, ac-cording to the WHO, this must have“priority status within public heath anddisease control programs.” However, lit-

tle progress has been made in recentyears, which is why bodies such as theUnited Nations and IFHHRO, an inde-pendent body dedicated to advancinghealth-related human rights globally, aretrying to redirect attention to the drive.

Among the most important points toemerge from the workshop discussionswere that: � Physicians and other health profes-sionals have an ethical duty to offer pa-tients with pain quality assessments, andto prescribe medications such as opioidsin adequate quantities to all in need, in-cluding children and others who may notbe able to express their pain clearly;� The right to pain management accessfor all people, without discrimination, aslaid down in professional standards andguidelines and in international law, shouldbe respected and effectively implemented;� Instruction on pain management, bothclinical and didactic, should be mandato-ry in medical and nursing curricula, andin continuing medical and nursing educa-tion. This includes instruction in evidence-based pharmacological treatment; and� It is necessary for health professionalsto play a major role in improving accessto essential medicines and in develop-ment of policies to ensure availability of,and access to, adequate pain treatment.

Neurological PerspectiveAlthough the participants did not specif-ically discuss the neurological aspects ofpain treatment, some of the principlesand working points that emerged fromthe workshop could be applicable in theneurological setting.

For example, improved education andtraining in pain and palliative care isnecessary for neurologists. The litera-ture confirms that neurologists involvedin the management of patients withbrain tumors and motor neuron diseasehave insufficient knowledge about paintreatment, supportive and palliativecare, and end-of-life treatment deci-sions, all of which are also necessary for

management of patients with degener-ative neurological diseases such as de-mentia, Parkinson’s disease, and ad-vanced multiple sclerosis (Neurology1999;53:284-93).

Medical associations have an impor-tant role to play to support pain treat-ment as a human right, and both painmanagement and palliative care shouldbe included in the mandatory medicaland nursing curricula, and continuingmedical and nursing education. ■

DR. PACE is the director of the neurologyunit at the National Cancer InstituteRegina Elena, Rome, Italy. He was theWFN representative at this summit.

Physician Education Is CrucialPain Treatment • from page 1

Worldwide, millions of peoplecontinue to suffer from severe

pain that often could be alleviated bydrug-based palliative care and painrelief. Apart from other reasons, suchas poverty and overall problems relat-ing to health care, restrictive drugpolicies have contributed to a situa-tion in which access to narcotic drugsis still severely restricted and some-times unavailable, in particular in theglobal South. I am of the opinionthat the de facto denial of access topain relief, if it causes severe pain

and suffering, constitutes cruel, inhu-man, or degrading treatment or pun-ishment. I therefore call on the Hu-man Rights Council to take up thequestion of drug policies in the lightof international obligations in thearea of human rights.

–Dr. Manfred Nowak, the U.N.’s Special Rapporteur on Torture and

Other Cruel, Inhuman, or DegradingTreatment or Punishment, in a March

2009 report to the United Nations’Human Rights Council.

‘Cruel, Inhuman, and Degrading’



Diabetes and hypertension were strongly and in-dependently associated with brain infarcts, aswell as with atrophic changes such as increasing

ventricular size and sulcal widening.The finding – from one of the first longitudinal imag-

ing studies to look at vascular risk factors and infarct – con-firms that “control of blood sugar and blood pressure inmidlife should reduce the likelihood of ischemic and at-rophic changes in the brain in subsequent decades,”wrote Dr. David S. Knopman and his colleagues (Neurol-ogy 2011 May 4 [doi:10.1212/WNL.0b013e31821d753f]).

Dr. Knopman of the Mayo Clinic in Rochester,Minn., and his colleagues looked at an initially middle-aged cohort of patients from the Atherosclerosis Riskin Communities (ARIC) study, which in 1987 recruit-ed nearly 16,000 adults aged 45-64 years from ForsythCounty, N.C.; Jackson, Miss.; selected suburbs of Min-neapolis, Minn.; and Washington County, Md.

The subset analyzed for current study included 1,812patients who underwent brain magnetic resonanceimaging (MRI) in 1994-1995; all of the patients were 55years and older at this time, and came from eitherForsyth County or Jackson.

Ten years later, between 2004 and 2006, the patientswere invited to undergo a follow-up MRI as well as vas-cular health assessments. Overall, 1,112 of these follow-up images were of sufficient quality for inclusion in thepresent study (689 females; mean age 61.7 years).

“Compared with current participants, those whodied, were ineligible, or refused to participate in the fol-low-up scan were older, had a much higher stroke rate,had a higher rate of diabetes and hypertension, and hadworse imaging at the baseline scan,” wrote the authors.

According to Dr. Knopman, at baseline, 50.3% of theincluded subjects had neither hypertension (defined assystolic blood pressure greater than 140 mm Hg, dias-

tolic pressure greater than 90 mm Hg, or use of antihy-pertensives in the past 2 weeks) nor diabetes (defined asfasting glucose greater than 126 mg/dL, nonfasting glu-cose greater than 200 mg/dL, self-reported history, ortreatment in the past 2 weeks). These patients were clas-sified as having “low vascular risk.” Patients with bothconditions were referred to as “high vascular risk” andmade up 9.2% of the total cohort studied, they added.

Among the high-risk group, incident infarcts wereseen in 32.6%, compared with 15.1% in the low vascu-lar risk group, and 20.1% in the overall cohort.

Moreover, the risk increased with disease severity, theauthors found. “Those in the highest tertile for bothfasting blood sugar and systolic blood pressure had a3.68 times higher risk (95% confidence interval, 1.89-7.19) of new infarcts compared with subjects in the low-est tertile for both conditions,” they added.

Diabetes alone was also associated with incident in-farct, independent of hypertension. Indeed, after ad-justing for multiple variables including age, sex, race,hypertension and prevalent stroke, having diabetes

conferred a nearly two-fold risk of incident infarct, com-pared with those patients without the condition (oddsratio, 1.96; 95% CI, 1.23-3.10).

Similarly, hypertension alone was associated with anOR for incident infarct of 1.58, compared with those pa-tients with normal blood pressure (95% CI, 1.08-2.30).

Looking at brain atrophic changes, Dr. Knopmanfound that most patients experienced a change in ven-tricular size, sulcal widening and white matter hyper-intensities over the 10-year period, and older age by it-self accounted for worsening in these categories.

However, vascular risk factors also played a role. In-deed, they found that 84.7% of patients in the high riskgroup, versus 73.2% in the low risk group, experiencedventricular size progression of one grade or moreover the study period.

Similarly, 76.5% of high risk patients versus 55.5% inthe low-risk group showed white matter hyperintensi-ty progression. And 80.0% of high-risk patients, versus69.6% of their low-risk counterparts, showed an in-crease in sulcal widening.

The authors found no race- or sex-specific interac-tions between changes in brain imaging and vascularrisk factors, they wrote.

According to the researchers, the strengths of thecurrent study are numerous, and include its large sam-ple size, biracial composition, extensive risk factor as-sessment at baseline, and decade-long follow-up.

However, they did concede several weaknesses.For one, they wrote, many subjects were lost over the

10 years of follow-up. However, “those persons whohad follow-up scans were healthier in all respects in-cluding lower burdens of vascular risk factors, and lesspathology on imaging,” they wrote.

Consequently, “our findings probably understate thelinks between diabetes and hypertension.” In addition,at the time of the initial scans, volumetric MRI was notyet available, making measurement over time of thatparticular parameter impossible, they noted. ■

Diabetes, Hypertension Tied to Brain InfarctMajor Finding: Over 10 years of follow-up, 32.6%of patients with hypertension and diabetes record-ed a brain infarct, compared with 15.1% of pa-tients without either of these conditions.

Data Source: The Atherosclerosis Risk in Com-munities (ARIC) Study.

Disclosures: Lead author Dr. Knopman disclosedbeing a deputy editor of Neurology, the journalin which this study was published. He also dis-closed relationships with Eli Lilly, the Elan Cor-poration, Baxter International, and Forest Labo-ratories. He and several other investigatorsstated they have received grants from the Na-tional Institutes of Health and the NationalHeart, Lung, and Blood Institute, which partiallyfunded the ARIC study.

VIT

AL

S

01_08wfn11_6.qxp 6/3/2011 4:19 PM Page 8

www.clinicalneurologynews.com

— We Write Medicine’s First Draft —Clinical Neurology News

Before the drugis approved...

Before the guidelineis issued...

Before the researchis published...

You read it first in

ne

h

THE LEADER

IN NEWS

AND

MEETING

COVERAGE

09_16wfn11_6.qxp 6/3/2011 4:24 PM Page 9


B Y C H R I S T O P H E R T. B E V E R

J R . , M D, M B A ; E R I C M . C H E N G,

M D, M S ; S A R A H T O N N, M P H ;

R E B E C C A S WA I N - E N G, M S ; A N D

R I C H A R D D U B I N S K Y, M D, M P H

Late in 2010, the American Academyof Neurology for the first time pub-lished its quality measures for neu-

rological practice. The measurement setswere for the management of patientswith Parkinson’s disease and for the careof patients with epilepsy (see sidebars.)Measurement sets for dementia, stroke,and peripheral neuropathy are in devel-opment.

Quality measures matter because gov-ernmental and private payers increas-ingly are linking reimbursement for ser-vices to reporting on measures of quality.

Currently in the United States, thelargest payer – the Centers for Medicareand Medicaid Services – has establishedthe Physician Quality Reporting System(PQRS), a pay-for-reporting programthat pays a small bonus to physicians (in-cluding neurologists) who successfullyreport on quality measures. In the Unit-ed Kingdom, the National Health Servicehas established a pay-for-performanceprogram for general practitioners,whereby a bonus is provided for meeting

quality-related targets. Worldwide, in-creasing health care costs coupled withpersistent and growing concerns aboutcare quality have driven payers towardprograms that attempt to measure andreward care quality.

Traditionally, most quality-measuredevelopment has been focused on pri-mary care conditions, such as diabetes,and on high-risk procedures, such ascoronary artery bypass surgery. The in-volvement of specialty organizations inthe development of quality measureshas been restrained by a lack of mem-bership support, limited technical ex-pertise, limited financial resources, andthe organizational roles as advocates ofthe specialty rather than as regulators ofthe specialty.

However, a recent survey in the Unit-ed States suggests that this is changing,with 35% of specialty organizations nowactively involved in quality-measure de-velopment. The following three con-cerns appear to be driving this change inattitude:� Specialist concern that quality mea-sures developed by others and incorpo-rated into payment programs may be dis-advantageous to them.

� Concern that quality measures relatedto specialty care will not be included inpay-for-performance programs. For ex-ample, for 2011, there are only a fewmeasures in PQRS that are relevant tooutpatient neurology. � Concern that maintenance of certifi-cation (MOC) requirements in the Unit-ed States require performance-in-practice(PIP) evaluations, which are based large-ly upon quality measures.

Recently passed health care reformlegislation in the United States providesa payment incentive for MOC and PIPparticipation. Given these changes, qual-ity measures are likely to play an in-creasingly important role in neurologi-cal practice, and the harmonization ofmeasures used by payers in pay-for-per-formance programs and in MOC is apriority.

Many neurologists want to know howquality measures are developed andwhether they are valid. The AmericanAcademy of Neurology (AAN) quality-measure development process is basedon a process developed by the AmericanMedical Association–convened PhysicianConsortium for Performance Improve-ment® (PCPI), which is made up ofmedical specialty societies, state medicalsocieties, and others interested in quali-ty and patient care. PCPI quality mea-sures are widely accepted and many havebeen incorporated into PQRS.

Quality-measure development topicsare chosen by experts based on gaps incare, available evidence, and the impor-tance of measuring quality of care. Pub-lished practice guidelines or consensuspaper recommendations are ranked by abroad multispecialty stakeholder workgroup (including subject matter experts,patient advocate representatives, payers,and technical experts) based on gaps incare, validity, feasibility of measurement,and importance of measuring quality ofcare.

Quality-measure specifications arethen drafted with an experiencedmethodologist to include a full quality-measure description, a numerator de-scribing the required action, a denomi-nator describing the eligible patientpopulation, and applicable exclusions.The draft quality measures are then re-viewed and refined by the work group atan in-person meeting. Technical specifi-cations (including billing and diagnosiscodes, and electronic health record spec-ifications) are added to the quality mea-sures. The refined measures are thenposted for a 30-day public comment pe-riod. The work group reviews everycomment received and considers re-wording measures to improve clarity ormodify content. The final quality mea-surement set is approved by the AANBoard of Directors.

For example, the Parkinson’s disease(PD) and epilepsy quality-measure setsstarted with 258 and 160 recommenda-tions, respectively, and the ranking yield-

ed 12 candidate draft quality measures foreach. The PD and epilepsy panels con-sisted of 28 and 40 experts. In all, 227 and291 comments were received on the PDand epilepsy quality-measure sets. The fi-nal measurement sets consisted of 10 PDand 8 epilepsy quality measures, respec-tively. Although these quality measureshave not yet been incorporated into

PQRS, they have been incorporated intodisease-specific modules for the AAN’sMOC PIP program, NeuroPI®. In addi-tion, the quality measures are undergoingtesting for validity and reliability.

The AAN has embarked on a quality-measure development program to pro-vide measures of neurological care forthese programs and for use in MOC,

state licensure programs, public report-ing, accountability, and quality-improve-ment programs. The AAN has adopteda quality-measure development processthat is intended to include broad stake-holder input, be transparent, and basethe measures on the highest level ofavailable evidence. Quality measures arevalued by important stakeholders inhealth care, and it is important that neu-rologists can use quality measures thatare relevant to their practice.

Please address correspondence andreprint requests to the American Acade-my of Neurology, 1080 Montreal Av-enue, St. Paul, MN 55116; or e-mail themat [email protected]. ■

The authors are members of the AAN’sQuality Measures and ReportingSubcommittee. They are all based in theUnited States. DR. BEVER is in thedepartment of neurology at the Universityof Maryland, and the research service anddepartment of neurology at the VA(Veterans Affairs) Maryland Health CareSystem, both in Baltimore. DR. CHENG isin the department of neurology at the

The American Academy of Neurology publishes itsmeasurements for Parkinson’s and epilepsy.

Quality Measures for Neurological Practice

It is importantthat neurologistscan use qualitymeasures that arerelevant to theirpractice.

DR. BEVER

Specialists worrythat qualitymeasuresdeveloped byothers may bedisadvantageousto them.

DR. CHENG

1. Annual PD Diagnosis ReviewAll patients with a diagnosis of PDwho had their PD diagnosis re-viewed, including a review of cur-rent medications and a review forthe presence of atypical features(such as falls at presentation and ear-ly in the disease course, poor re-sponse to levodopa, symmetry atonset, rapid progression [to Hoehnand Yahr stage 3 in 3 years], lack oftremor, or dysautonomia) at leastannually.2. Psychiatric Disorders or Distur-bances AssessmentAll patients with a diagnosis of PDwho were assessed for psychiatric dis-orders or disturbances (such as psy-chosis, depression, anxiety disorder,apathy, or impulse control disorder)at least annually. 3. Cognitive Impairment or Dys-function AssessmentAll patients with a diagnosis of PDwho were assessed for cognitive im-pairment or dysfunction at least an-nually.4. Querying About Symptoms ofAutonomic Dysfunction All patients with a diagnosis of PD(or caregivers, as appropriate) whowere queried about symptoms ofautonomic dysfunction (such as or-thostatic hypotension, constipation,urinary urgency/incontinence,fecal incontinence, urinary reten-tion requiring catheterization, orpersistent erectile failure) at leastannually.5. Querying About Sleep Distur-bances All patients with a diagnosis of PD(or caregivers, as appropriate) who

were queried about sleep distur-bances at least annually.6. Querying About Falls All visits for patients with a diagnosisof PD in which patients (or care-givers, as appropriate) were queriedabout falls.7. PD Rehabilitative Therapy Op-tions All patients with a diagnosis of PD(or caregivers, as appropriate) withwhom rehabilitative therapy options(such as physical, occupational, orspeech therapy) were discussed atleast annually.8. Counseling on PD-Related Safe-ty Issues All patients with a diagnosis of PD(or caregivers, as appropriate) whowere counseled about context-specif-ic safety issues appropriate to the pa-tient’s stage of disease (such as in-jury prevention, medicationmanagement, or driving) at leastannually.9. Querying About PD Medica-tion-Related Motor Complications All visits for patients with a diagnosisof PD in which patients (or care-givers, as appropriate) were queriedabout Parkinson’s disease medica-tion-related motor complications(such as wearing off, dyskinesia, oroff-time).10. Review of PD Medical and Sur-gical Treatment Options All patients with a diagnosis of PD(or caregivers, as appropriate) whohad the PD treatment options (suchas nonpharmacologic treatment,pharmacologic treatment, or surgi-cal treatment) reviewed at least onceannually.

AAN’s Final 10 Parkinson’s Measures


09_16wfn11_6.qxp 6/3/2011 4:25 PM Page 10


FROM THE JOURNAL OF THE NEUROLOGICAL SCIENCES

Oromandibular Dystonia in Japanese EncephalitisThe flaviviruses encompass a broad group of pos-

itive-sense, single-stranded, enveloped virusesthat include agents that cause two basic syn-

dromes: viral fevers and encephalitis. Examples ofthese two syndromes would include yellow, WestNile, and dengue fevers; and Japanese, West Nile, StLouis, Powassan, Rocio, Far Eastern, and Central Eu-ropean tick-borne encephalitis. Some of these syn-dromes, such as Rocio and Powassan, are re-stricted to certain parts of the world,whereas others, such as West Nile virus,have spread worldwide in recent years. Oth-ers, such as dengue and Japanese en-cephalitis ( JE), are currently geographical-ly restricted but have been spreading inrecent years.

The encephalitides caused by flavivirusescan have a very broad range of manifesta-tions. In addition to febrile encephalopathy,focal weakness, and seizures, the symp-toms can include movement disorders,myelopathy, and anterior horn cell disease.JE, in particular, is known for its association withmovement disorders with tremors, rigidity, and atheto-sis. Pathological examination shows inflammatorychanges in the brainstem and basal ganglia, as well asin the cortex.

These observations were made in the first half ofthe 20th century, especially after World War II, whenAllied troops occupied Japan and Southeast Asia.Several epidemics of JE provided researchers with theopportunity to study this disease, though initially, ithad to be differentiated from von Economo’s en-cephalitis (encephalitis lethargica), which has its owndistinctive movement disorder. As experience with JEaccumulated, the clinical syndromes associated withit were better delineated and studied. JE continues toprovide opportunities to correlate signs and symp-toms with pathology and imaging. Some new resultsare described in the current study by Jayantee Kalitaand colleagues ( J. Neurol. Sci. 2011;304:107-10).

Their study concerns oromandibular dystonia(OMD), in which sustained postures of the oral, buc-

cal, and lingual muscles occur, thus interfering withspeech, chewing, and swallowing. OMD was studiedin patients with JE. The overall differential diagnosisof OMD is rather long and includes metabolic, neu-rodegenerative, postinfectious, posttraumatic, andmedication neurotoxicity. The most likely causes ofOMD depend on where in the world it occurs. InSoutheast Asia, infections are the most common

cause. In the West, degenerative diseasesand medications are more likely.

Dr. Kalita and colleagues identified 209patients with encephalitis, defined as afebrile encephalopathy with pleocytosisand exclusion of bacterial or fungal in-fection, septicemia, or malaria. Of these,17 patients who had OMD were selectedfor detailed study, giving a rough esti-mate of 8% of JE pa-tients having OMD,at least in this popu-lation. Fourteen ofthese patients had JE;

the other three were nonspecific(NS) with no clear-cut viral causeestablished. The patients werestudied with routine testing, aswell as MRI and SPECT scans ofthe brain. The researchers fol-lowed up the patients to ascertain long-termoutcome.

As might be expected, MRIs showed abnormalitiesin the central gray structures (basal ganglia, thala-mus, brainstem) as well as cortex in all 16 JE OMDpatients studied. Of the three NS OMD patients, thescans were normal for two. The SPECT scans, whichmeasure perfusion, were abnormal in 7 of 10 patientstested, and showed hypoperfusion in the thalamusand basal ganglia as well as the frontal, parietal, andtemporal cortices. Thus, both the cortical and deepgray structures were affected in JE, consistent withconfusion and seizures as well as movement disor-ders. Although the dystonia would be expected withdeep gray structure involvement, there was no

detailed correlation between the precise movementdisorder and MRI lesions; however, this is not sur-prising in a study with relatively small numbers ofpatients.

The outcomes were not encouraging, with persis-tent deficits in both the dystonia and other effects ofthe widespread encephalitis. The degree of OMDonly partially correlated with the other deficits, suchas dystonias elsewhere. Improvement was often notcomplete, and recovery took months. The OMD re-solved in six patients, improved in two, and was un-changed in seven. Including all the deficits, only 2 of14 patients made complete recoveries; of note isthat 2 of the 3 NS patients recovered completely by9 months.

The study is intriguing for several reasons. It wouldbe interesting to compare the JE OMD with JE with-

out OMD, especially if onewants to know the sensitivity andspecificity of imaging. Thus, inthis group of patients, is there ahint of a difference in the MRIand SPECT scans between the JEOMD and JE without OMD pa-tients? If so, this might providepathogenetic hints, laying theground for the use of advancedimaging technologies such as

magnetic transfer imaging, diffusion tensor imaging,and magnetic resonance spectroscopy.

The study provides an example of how a viral in-fection of selected brain structures can lead to deficitsthat have been seen with other diseases affectingthose same structures. It would be interesting toknow whether the selective involvement of the cen-tral gray structures implies a viral receptor or otherspecific molecule that is also involved in a genetical-ly aberrant metabolic process, when mutated, in thesusceptible cells? What is common to OMD caused byJE and, for example, Wilson’s disease or postanoxic en-cephalopathy?

There are still ideas to develop and opportunities totake. ■

BY ALEX TSELIS, MD, PHD

University of California, Los Angeles, and the departmentof neurology at VA Greater Los Angeles Healthcare. MS.TONN and MS. SWAIN-ENG are with the AAN in SaintPaul, Minn. DR. DUBINSKY is in the department ofneurology at the University of Kansas, Kansas City.

ReferencesCheng EM, Tonn S, Swain-Eng R, Factor S, Weiner

WJ, Bever Jr CT. Quality improvement in neurolo-gy: AAN Parkinson’s disease quality measures.Neurology 2010;75:2021-7

Fountain NB, VanNess PC, Swain-Eng R, Tonn S,Bever CT. Quality improvement in neurology: AANepilepsy quality measures. Neurology 2011;76:94-9

AAN Quality Page:www.aan.com/go/practice/quality

AAN NeuroPI page: www.aan.com/practice/pip American Board of Psychiatry and Neurology

(ABPN): www.abpn.com AMA convened Physician Consortium for Perfor-

mance Improvement® (PCPI): www.ama-assn.org/ama/pub/physician-resources/clinical-practice-improvement/clinical-quality/physician-consor-tium-performance-improvement.page

Physician Quality Reporting System (PQRS):www.cms.gov/PQRSs

1. Seizure type and current seizure frequencyAll visits with the type of seizure and currentseizure frequency for each seizure type document-ed in the medical record.2. Documentation of etiology of epilepsy orepilepsy syndromeAll visits with the etiology of epilepsy or epilepsysyndrome reviewed and documented if known, ordocumented as unknown or cryptogenic.3. EEG results reviewed or requested, or a testorderedAll initial evaluations with the results of at leastone EEG reviewed or requested, or – if EEG wasnot performed previously – an EEG ordered. 4. MRI/CT scan reviewed or requested, or a scanorderedAll initial evaluations with the results of at leastone MRI or CT scan reviewed or requested, or – ifan MRI or CT scan was not obtained previously –an MRI or CT scan ordered (MRI preferred). 5. Querying and counseling about antiepilepticdrug side effectsAll visits in which patients were queried and coun-seled about antiepileptic drug side effects, and the

querying and counseling were documented in themedical record.6. Surgical therapy referral consideration for in-tractable epilepsyAll patients with a diagnosis of intractable epilepsywho were considered for referral for a neurologicalevaluation of appropriateness for surgical therapy,and the consideration was documented in the med-ical record within the past 3 years.7. Counseling about epilepsy-specific safety issuesAll patients who were counseled about context-spe-cific safety issues appropriate to the patient’s age,seizure types and frequencies, occupation, leisureactivities, and other relevant factors (for example,injury prevention, burns, appropriate driving re-strictions, or bathing) at least once per year.8. Counseling for women of childbearing poten-tial with epilepsyAll female patients of childbearing potential (aged12-44 years) diagnosed with epilepsy who werecounseled at least once per year about epilepsy andhow its treatment may affect contraception andpregnancy.

AAN’s Final 8 Epilepsy Measures Continued from previous page

JAPANESE ENCEPHALITIS ISKNOWN FOR ITS ASSOCIATIONWITH MOVEMENT DISORDERS

WITH TREMORS, RIGIDITY,AND ATHETOSIS.

09_16wfn11_6.qxp 6/3/2011 4:25 PM Page 11

MULTIPLE SCLEROSISAND RELATED DISORDERS

Call For PapersAims and ScopeMultiple Sclerosis is an area of ever expanding research and escalating publications. Multiple Sclerosis and Related Disorders is a wide ranging international journal supported

by key researchers from all neuroscience domains that focus on MS and associated disease

of the nervous system. The primary aim of this new journal is the rapid publication of high

quality original research in the field. Important secondary aims will be timely updates and

editorials on important scientific and clinical care advances, controversies in the field, and

invited opinion articles from current thought leaders on topical issues. One section of the

journal will focus on teaching, written to enhance the practice of community and academic

neurologists involved in the care of MS patients. Summaries of key articles written for a lay

audience will be provided as an on-line resource.

A team of four chief editors is supported by leading section editors who will commission

and appraise original and review articles concerning: clinical neurology, neuroimaging,

neuropathology, neuroepidemiology, therapeutics, genetics / transcriptomics, experimental

models, neuroimmunology, biomarkers, neuropsychology, neurorehabilitation, measurement

scales, teaching, neuroethics and lay communication.

AudienceAll branches of neuroscience: clinical neurologists, neurophysiologists, geneticists, psychologists,

molecular biologists, MRI and allied imaging specialists, immunologists, major pharmaceutical

companies, ethical and legal specialists, MS specialist nurses, drug trial nurses.

Type of articles

On-line summary of selected papers of relevance for lay audience

Video presentations of informative cases or webcasts of conference debates could be

included as supplementary material. We would encourage correspondence and that

would be web based.

• Editorials

• Commentaries

• Original papers

• Clinical Trial papers

• Reviews

• Letter to the Editors

• Case Reports

• Correspondence

• Book reviews

• News

• Teaching Lessons

Chief Editors

Professor Gavin Giovannoni

PhD, FCP, FRCP, FRCPath.

Professor Christopher H Hawkes

MD FRCP

Professor Fred D. Lublin, MD

Dr Brenda Banwell MD

MSARD-journal.com

ISSN: 2211-0348

Catalogue 2012: Volume 1 in 4 issues

Advance issue in October 2011

To submit a

paper, go to:

ees.elsevier.com/

msard/


Calendar of International Events2011International Brain ResearchOrganization World Congress ofNeuroscienceJuly 14-18, Florence, Italywww.ibro2011.org/site/home.asp

Congress of the Pan-Asian Committee forTreatment and Research in MultipleSclerosisAug. 28-30, Singapore, Malaysiawww.pactrims.org

International Epilepsy CongressAug. 28-Sep. 1, Rome, Italywww.epilepsyrome2011.org

International Congress of the WorldAssociation of Sleep Medicine andCongress of the Canadian Sleep SocietySep. 10-15, Quebec City, Canadawww.wasm2011.org

American Association of Neuromuscular& Electrodiagnostic Medicine AnnualMeetingSep. 14-17, San Francisco, USAwww.aanem.org/Meeting/Annual-Meeting.aspx

Asia Pacific Stroke ConferenceSept. 29-Oct. 1, Colombo, Sri Lankaswww.apsc2011.com

Association of British NeurologistsAnnual MeetingOct. 5-7, Newcastle, UKwww.theabn.org/Meeting.aspx?type=1

World Congress of the World SleepFederationOct. 16-20, Kyoto, Japanwww.worldsleep2011.jp/index.html

Int. Congress on Vascular DementiaOct. 20-23, Riga, Latviawww.kenes.com/vascular

20th World Congress of NeurologyNov. 12-17, Marrakesh, Moroccowww2.kenes.com/wcn/Pages/Home.aspx

2012European Neurological Conference onClinical Practices: Neurovascular andNeurodegenerative DiseasesJan. 27-29, Warsaw, Polandwww.enccp.net

World Stroke CongressOct. 10-13, Brasilia, Brazilwww2.kenes.com/stroke/Pages/Home.aspx

09_16wfn11_6.qxp 6/3/2011 4:28 PM Page 12


MOVIE REVIEW

Was George VI’s Impediment a Form of Action Dystonia?“The King’s Speech”

Directed by Tom HooperFeaturing Colin Firth and Geoffrey Rush

The movie “The King’s Speech” created quite a stirrecently when it was nominated for 12 Oscarawards and Colin Firth bagged the Best Actor

award for his remarkable portrayal of King George VI’sstruggle to conquer his speech im-pediment of stuttering.

The plot focuses on the reluctantmonarch who succeeds his brotherEdward after the latter abdicatesand soon after that has to give themost important speech of his life –a radio address to the British peopleannouncing that England had de-clared war on Germany. The moviehighlights the predicament of peo-ple who stutter and the situations and factors that canaggravate the condition; in George’s case, these in-cluded his harsh treatment at the hands of a nanny andbeing forced to become right handed. However, themovie also provides an opportunity to revisit this con-dition and consider it in a neurological sense: Is this con-dition a manifestation of basal ganglia dysfunction ora form of dystonia?

In medical parlance, stuttering or stammering is typ-ically defined as involuntary dysfluency in verbal ex-pression. Usually, stuttering manifests as repetitions ofsounds, syllables, or words, or as speech blocks or pro-longed pauses between sounds and words. Develop-mental stuttering occurs in about 1.4% childrenyounger than 10 years, is mostcommon in young boys, andresolves by adulthood in near-ly 80% of children1. Less than1% of adults stutter, 80% ofwhom are men.1,2

The exact pathophysiologyof stuttering has not beenclearly defined. There aresome striking similarities be-tween stuttering and focal dys-tonias that lead inevitably tothe question: Is stuttering aform of dystonia? In themovie, some of these featuresare illustrated in a very con-vincing way. Stressful situa-tions such as having to talk infront of the public worsenedthe king’s stuttering, and this isusually seen in dystonia aswell. More important, though,is the clear suggestion that itwas the manipulation of thesensory input that had an effect in stuttering, which isalso a characteristic feature of dystonia. For example,in the movie, the king wouldn’t stutter while he wassinging or if he couldn’t hear his voice, as was the casewhen his speech therapist Lionel Logue (GeoffreyRush) had him speak while listening to loud classicalmusic through headphones. Indeed, altered auditoryfeedback such as singing, choral speaking, masking, anddelayed or frequency-altered feedback have long beenknown to reduce stuttering.3

A similar effect can be demonstrated by the ‘‘sensorytrick’’ in dystonia; for example, tactile sensory stimulationof the affected body part often dramatically reduces themuscular contractions. Another similarity between stut-tering and dystonia is the task specificity. Some types ofdystonia affect highly automated sequential motor tasks

such as writing with a pen (writer’s cramp), typing, orplaying a certain musical instrument (musician’s dysto-nia). Stuttering is also highly task specific because the mo-tor problems are limited to speech. The symptoms ofstuttering are often reduced if the stutterer changes to anonautomatic way of speaking such as speaking with aforeign accent. That resembles the techniques patientswith task-specific dystonia use to overcome their symp-

toms, such as using different fingers to hold a pen orchanging its size or altering their instrument. As alreadymentioned, stuttering tends to disappear after childhood;the reason for that is not clear, but certain dystonic con-ditions can also go into remission or adapt.

With regard to causation, environmental psychosocial(stress, or negative experiences associated with speaking)and genetic factors have been implicated. Researchersnow believe that an underlying genetic trait contributesto about 70% of the variance in liability for stuttering,whereas the remaining 30% are due to environmentalfactors.4,5 Genetic factors also underpin various formsof dystonia. In this regard, it is interesting to note thata recent study showed increased susceptibility to stut-

tering in Han Chinese patients by the presence of theC allele at rs6277 in the dopamine D2 receptor gene,whereas the T allele was protective.6 D1 receptor genepolymorphisms have also been implicated in focal cer-vical dystonia and blepharospasm.7,8 This is also inter-esting as the dopaminergic system is implicated in var-ious forms of dystonia. However, more recently agenetic defect was identified in consanguineous Pak-istani families and unrelated individuals from Pakistanand North America. They were found to have mutationsin the lysosomal function–related GNPTAB, GNPTG,and NAGPA genes that were associated with stuttering.9

It is not clear whether these genetic defects underlie allpatients with stuttering, and it is more likely that this isa genetically heterogeneous disorder.

A common pathophysiologic basis of stuttering and

dystonia is feasible. It’s likely that stuttering may be dueto be an impaired ability of the basal ganglia and in par-ticular the putamen to produce timing cues for the ini-tiation of the next motor segment in speech,10 and ac-quired stuttering has been reported after basal ganglialesions. Basal ganglia lesions and dysfunction are wellrecognized in the causation of dystonia.11,12 Support-ive to that is our personal clinical experience, of patients

who had stuttering in childhoodthat improved in adulthood, onlyto return when they developedbasal ganglia disorders like Parkin-son’s disease or adult-onset pri-mary dystonia. One of the mostcommon causes of severe stutter-ing is Fahr’s syndrome, wherethere is bilateral basal ganglia cal-cification. A common pathophys-iologic basis is also supported by

a recent electrophysiologic transcranial magnetic stim-ulation study showing that patients with stuttering havereduced short intracortical inhibition,13 which is rec-ognized as a key electrophysiologic feature in dystoniaas well.

“The King’s Speech” should again draw our attentionto those who are affected by this disorder of chronicstuttering. These individuals have great difficulty com-municating in key situations, a diminished satisfactionof life, and a reduced ability to achieve their goals.14 Fur-ther understanding of the fundamental pathophysiol-ogy of this disorder is important in order to develop ef-fective treatments. ■

References1. Craig et al (2002) Epidemiology of stuttering inthe community across the entire life span. J. SpeechLang. Hear. Res. 2002;45:1097-105.2.Yairi E, Ambrose NG (1999) Early childhood stut-tering I: persistency and recovery rates. J. SpeechLang. Hear. Res. 1999;42:1097-112.3. Prasse JE, Kikano GE (2008) Stuttering: anoverview. Am. Fam. Physician 2008;77:1271-6.4. Andrews et al (1991) Genetic factors in stutteringconfirmed. Arch. Gen. Psychiatry 1991;48:1034-5.5. Felsenfeld et al (2000) A study of the genetic andenvironmental etiology of stuttering in a selectedtwin sample. Behav. Genet. 2000;30:359-66.6. Lan et al (2009) Association between dopaminer-gic genes (SLC6A3 and DRD2) and stuttering amongHan Chinese. J. Hum. Genet. 2009;54:457-60.7. Placzek et al (2001) Cervical dystonia is associatedwith a polymorphism in the dopamine (D5) receptorgene. J. Neurol. Neurosurg. Psychiatry 2001;71:262-4.8. Misbahuddin et al (2002) A polymorphism in thedopamine receptor DRD5 is associated with ble-pharospasm. Neurology 2002;58:124-6.9. Kang et al (2010) Mutations in the lysosomal en-zyme-targeting pathway and persistent stuttering. N.Engl. J. Med. 2010;362:677-85.10. Alm PA (2004) Stuttering and the basal gangliacircuits: a critical review of possible relations. J. Com-mun. Disord. 2004;37:325-69.11. Berardelli et al (1998) The pathophysiology ofprimary dystonia. Brain 1998;121:1195-212.12. Hallett M (2006) Pathophysiology of dystonia J.Neural. Transm. Suppl. 2006;70:485-8.13. Neef et al (2011) Reduced intracortical inhibitionand facilitation in the primary motor tongue repre-sentation of adults who stutter. Clin. Neurophysiol.2011 Mar. 4 (doi:10.1016/j.clinph.2011.02.003).14. Yaruss JS (2010) Assessing quality of life in stutter-ing treatment outcomes research. J. Fluency Disord.2010;35:190-202.

BY KAILASH BHATIA, MD

Dr. Bhatia is lab head of theClinical Movement DisordersGroup at the Sobell Departmentof Motor Neuroscience andMovement Disorders in theInstitute of Neurology at theUniversity College of London.

MARIASTAMELOU, MD

Dr. Stamelou is inthe department ofneurology, PhilippsUniversity,Marburg, Germany.

King George (Colin Firth) spoke fluidly if he couldn’t hear his voice or whenhe sang – a variation of the “sensory trick” sometimes used to treat dystonia.

CO

UR

TE

SY

LA

UR

IES

PA

RH

AM

/TH

EW

EIN

ST

EIN

CO

MP

AN

Y

09_16wfn11_6.qxp 6/3/2011 4:29 PM Page 13


BOOK REVIEW

Demystifying Neurology for Students and TeachersClinical Neurology: A Primer

By Peter GatesPublished by Churchill Livingstone

Elsevier, Australia, 2010.

Several recent studies have suggest-ed that medical students and resi-dents have significant difficulty in

diagnosing and managing patients withneurological illnesses.

One of the problems of current med-ical education is lack of integration ofbasic neurosciences (anatomy and phys-iology, in particular) and clinical neu-rosciences into a cohesive whole. As aresult of this, the novices in clinical neu-

rology – medical students and juniorresidents – find it hard to reasonthrough the day-to-day neurologicalproblems in their patients, and the sub-ject of neurology has come to beviewed as a complex, difficult subspe-cialty in medicine.

Students’ fear of clinical neurology

can be defined as “neurophobia”; strongbasic integration of neurosciences/clin-ical neuroscience should be able to curethis condition.

Where Science Meets PracticeThere is already a wealth of textbooksin neurology for general audiences, se-nior residents, and practicing neurolo-gists, but neurology text books intend-ed for novices or medical students arefew and far between.

Now, Prof. Peter Gates, who is asso-ciate professor of neurology at Univer-sity of Melbourne and Deakin Univer-

sity, Melbourne, has written a bookthat is an excellent resource for neu-rology teaching. Clinical Neurology: APrimer will help instructors demon-strate to their students the strong inte-gration between the basic neuro-sciences and clinical neurosciences,allowing students to enjoy and betterunderstand this fascinating subspecial-ty of medicine.

I thoroughly enjoyed this book. Prof.Gates, who is also director of stroke, di-rector of neuroscience, and director ofphysician training at Barwon HealthGeelong, Victoria, has successfully de-mystified the myth of neurology as adifficult subspecialty, and readers of hisbook will come to see how easy and en-joyable it is to learn and practice neu-rology. A high-quality, high-resolutionDVD that comes with the book reiter-ates and demonstrates key aspects ofthe text.

Always With a Clinical PerspectiveThe first chapter of the book presentsan innovative, thought-provoking ap-proach to clinically oriented neu-roanatomy.

Prof. Gates goes through the relevantneuroanatomy from a clinical view-point, introducing the concept of themeridians of longitude and parallels ofthe latitude to liken the nervous systemto a map grid.

The descending motor pathway fromthe cortex to the muscle, the ascendingsensory pathway for pain and temper-ature, and the ascending sensory path-way for vibration and proprioceptionare the meridians of longitude. Thecerebral cortex and the cranial nerves ofthe brainstem (central nervous system)and nerve roots and the peripheralnerves (peripheral nervous system) are

BY TISSAWIJERATNE, MD

Dr. Wijeratne isdirector of theStroke Unit andNeuroscienceResearch Unit,Western Hospital,

Footscray, Victoria, Australia.


09_16wfn11_6.qxp 6/3/2011 4:30 PM Page 14


OBITUARY

Clark Millikan, MD (1915-2011)B Y R O B E R T J. J OY N T,

M . D. , P H . D.

Clark Millikan, a noted authorityon stroke and cerebrovascular dis-ease, died Jan. 29, 2011, in Utah at

age 95. He had been the first editor ofthe journal, Stroke; was the first chair-man of the American Heart Associa-tion’s stroke council; and was presidentof the American Neurological Associa-tion from 1973 to 1974.

Dr. Millikan was born in Freeport, Ill.,March 2, 1915. In 1939, he graduatedwith a medical degree from the Univer-sity of Kansas Medical School, KansasCity. He completed a surgical and a med-ical internship but became fascinatedwith neurology and went on to completehis neurology training at the Universityof Iowa, Iowa City, under Clarence VanEpps and Adolph Sahs.

I met Clark while I was at Iowa as ajunior medical student rotating throughneurology. I remembered his humorand humanity with patients. He was ameticulous examiner, bringing out signsthat we as medical students had notfound. Even then, he always wore apearl-headed pin in his lapel, ready to doa neurological examination on anyonepassing by. This practice continuedthroughout his career.

Clark left Iowa in 1950 to join the

Mayo Clinic in Rochester, Minn. Sometime after that, while I was on the staffat Iowa, I had an unusual case involvinga patient with severe polymyositis andParkinsonism. I treated him for each ofthe diseases. On the patient’s returnvisit, he informed me that I was “ very

good” as he had gone to the Mayo Clin-ic – a custom of Iowans seeking a sec-ond opinion – and the famous neurolo-gist Clark Millikan arrived at the samediagnosis.

I was emboldened by this confirma-tion and I decided to report the case.However, in the next Proceedings of theMayo Clinic, Clark had published an ar-ticle titled, “Unusual Combination ofPolymyositis and Parkinsonism.” Yearslater when I reminded him of this, he re-minded me that “to the swift belongs therace.” Of course, he didn’t know I hadseen the patient and correctly diagnosedhim before he went to the Mayo.

Clark was chairman of neurology atthe Mayo Clinic from 1955 to 1966. Itwas during this time that extracranialvascular disease was found to be thecause of many strokes, and Clark de-voted much of his attention to this areaof study. During this time, he was alsofounding editor of Stroke and he servedon the American Board of Psychiatryand Neurology. From 1976 to 1987,when he was professor of neurology atthe University of Utah, in Salt LakeCity, Clark was elected president of theAmerican Neurological Association. In1997, Clark and his wife, Dr. NancyFutrell, a pediatric neurologist, co-founded the Intermountain StrokeCenter in Salt Lake City, where the

focus was on diagnosing, treating, andpreventing stroke.

Throughout his distinguished career,Clark trained many loyal residents. Inaddition to being a master clinician andteacher, his intellectual prowess andrestless curiosity were the driving forcebehind the 250 scientific articles pub-lished during his lifetime.

Clark was a wonderful tennis player,and any excuse to pursue this passionwas taken. He also was a fly fisherman,a horseman, and a woodworker. I re-member traveling with him on a long,bumpy flight during which the lightning,on occasion, seemed very close to thecraft. But Clark sat calmly knitting asweater throughout.

Nancy was his devoted wife of 23years. He had three children, William,Terry, and Jeffrey; four grandchildren;and five great-grandchildren.

I met Clark and Nancy at many meet-ings. He thought I looked like one ofthe previous Popes and would gothrough a rather irreverent greeting be-fore telling me some new story or jokethat he had picked up. I remember himmostly for his kindness to younger col-leagues and his upbeat affability. ■

DR. JOYNT is Distinguished UniversityProfessor at the University of RochesterMedical Center, New York.

Clark Millikan was a respected experton stroke and cerebrovasculardisease, an inspiring teacher andmentor, and compassionate clinician.

CO

UR

TE

SY

DR

. N

AN

CY

FU

TR

EL

L

the parallels of latitude.Having established that grid concept, Prof. Gates

explains that if the patient has weakness, then thepathological process must be affecting the motorpathway somewhere between the cortex and themuscle, whereas if there are sensory symptoms, thepathology must be somewherebetween the sensory nerves inthe periphery and the corticalsensory structures. It is the pat-tern of weakness and sensorysymptoms/signs together withthe parallels of latitude that areused to determine the site ofpathology.

Prof. Gates uses the followingexamples that combine weak-ness with various parallels oflatitude to help explain this con-cept. (The parallels of latitudefollow the plus sign.)� Weakness + marked wasting: the peripheral nervoussystem, because marked wasting does not occur withcentral nervous system problems.� Weakness + cranial nerve involvement: the brain-stem� Weakness + visual field disturbance ( not diplopia)or dysphasia: the cortex� Weakness in both legs + loss of pain and tempera-ture sensation in the torso: the spinal cord

A number of case studies and simple illustrations areused to clarify the matters in an easily digestible wayfor the novice reader in clinical neurology.

A chapter on neurological history taking outlinesthe basic principals and the skills needed to take an ef-

fective neurological history. Again, case studies areused to demonstrate and as the basis for discussion ofthe pivotal components of history taking. In addition,the reader gets to see Lord Walton of Detchant, thenoted English neurologist, taking a neurological his-tory from a patient in a segment in the accompany-ing DVD.

The DVD is an important, enriching component ofthis work. The reader canalso observe demonstra-tions on neurological ex-amination technique, forexample, one in whichProf. Gates demonstrateshow to perform the clini-cal exam of cranial nervesand upper and lowerlimbs.

Undergraduate andpostgraduate students willfind such footage of ac-complished, experiencedneurologists in action an in

valuable resource in mastering clinical neurology skills.A chapter on the cranial nerves and understanding

the brainstem, is particularly useful. Here, Prof. Gatesintroduces his “Rule of Four,” a simple method to un-derstand the anatomy of brain stem and the complexbrain stem vascular syndromes:� There are four structures in the midline (the para-median aspect of the midbrain adjacent to the midline)beginning with M: motor nucleus, median longitudi-nal fasciculus, medial lemniscus, and the motor path-way (corticospinal tract).� There are four structures to the side (lateral) be-ginning with S: Spinocerebellar pathway, Spinothal-amic pathway, Sensory nucleus of the 5th cranial

nerve, and the Sympathetic pathway.� There are four cranial nerves in the medulla(12th, 11th, 10th, and 9th cranial nerves); four in thepons (8th, 7th, 6th, and 5th cranial nerves), fourabove the pons (4th and 3rd cranial nerves in themidbrain, and 2nd and 1st cranial nerves outside themidbrain).� The four motor nuclei that are in the paramedianregion are those that divide equally in to 12 except for1 and 2 cranial nerves: 3rd, 4th, 6th, and 12th cranialnerves.

Again, visuals – this time diagrammatic – are used toillustrate and further simplify the rule.

In a chapter titled “After the History and Exami-nation, What Next?” Prof. Gates describes all of thepossibilities that could arise by the end of the histo-ry and examination, from “no idea what is the clini-cal problem is” to “seeking another opinion.”

In my opinion, his response to this question is rev-olutionary in a clinical neurology text book that isaimed at medical students and junior residents. Byencompassing this range of possibilities, Prof. Gatespaints an honest and accurate picture of clinical prob-lem solving in the real world setting, which shouldgive the reader an appreciation and understanding ofcomplexities of this nuanced process.

Substantial and Accessible InformationProf. Gates’s book is intended for medical studentsand young doctors, yet, as teacher of neurology, Ifound it extremely useful.

For teachers, it offers a range of instructive toolsand techniques, as well as clinical information that isboth substantial and accessible. But most important,this book will help many medical students and youngresidents come to enjoy neurology as the fascinatingsubject that it is. ■

Continued from previous page

BY ADDRESSING A RANGE OFPOSSIBILITIES IN ANSWERING

CLINICAL QUESTIONS,PROF. GATES PAINTS AN HONEST AND

ACCURATE PICTURE OF PROBLEMSOLVING IN THE REAL WORLD SETTING

AND THE COMPLEXITIES OF THISNUANCED PROCESS.

09_16wfn11_6.qxp 6/3/2011 4:31 PM Page 15

09_16wfn11_6.qxp 6/3/2011 4:31 PM Page 16

Documents

01 08wfn11 6 - World Neurology · patients were diagnosed with os-teoporosis of the spine based on QCT T scores of less than 3.1 and/or a Z score of less than 1.5. Ten patients had