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VOL. 25 • NO. 5 • OCTOBER 2010 World Neurology

THE OFFICIAL NEWSLETTER OF THE WORLD FEDERATION OF NEUROLOGY Neurological Care Under Scrutiny in Africa INSIDE Ukraine BY SUSAN W. MARINO, suance of the United Nations The WFN’s Parkinsonism PH.D. Millennium Development Goals and Related Disorders in 2000, the establishment of the isorders of the nervous President’s Emergency Plan for Research Group holds a EWS system produce a chal- AIDS Relief (PEPFAR) program N movement disorders lenging and largely un- by George W. Bush in 2003, and course in Lviv, marking

D EDICAL

mitigated disease burden in growing support from nonprof- M the Federation’s first many countries in the sub- it organizations such as the meeting in Ukraine. Gates Foundation. The organiz- LOBAL Saharan region, yet there is a se- G PAGE 8 vere shortage of people who ers of the Kampala meeting are trained in the treatment of hoped to emulate that effort for LSEVIER United States psychiatric and neurological MNS disorders. /E conditions, and appropriate Researchers studying

ARRELL human embryonic stem medications and equipment are Numbers Count H in short supply, if available at all. Good epidemiological data are cells are trapped in a Last year, the Uganda Na- needed for two purposes – to de- legal quagmire over the ATHERINE tional Academy of Sciences’ Fo- vise a strategy for improving C federal government’s rum on Health and Nutrition quality of care and to convince Sound data on the nature and extent of mental, neurological, and policy on funding for government policy makers, who substance-use disorders are needed, says Dr. Susan W. Marino. and the US-based Institute of research using the cells. Medicine’s Forum on Neuro- need to see evidence to act. science and Neurological Dis- For the latter, data on the ef- ly an extreme underreporting of ment needs related to HIV/ PAGE 10 orders hosted a workshop in fectiveness of treatment and the burden of MNS disease in AIDS, malaria, tuberculosis, and Kampala, Uganda, at which rep- treatment delivery systems are sub-Saharan Africa. Affected pa- other infectious diseases are so Ethiopia resentatives from the medical, needed in addition to accurate tients often are hidden by their great that MNS disorders are Tetanus continues to academic, and governmental baseline information. The World families because of the stigma often misdiagnosed, over- contribute to a communities of 16 countries Health Organization anticipates and superstition associated with looked, and underreported. significant neurological met to address the quality of that the prevalence of MNS dis- mental disease and epilepsy, and This is exacerbated by the short- burden and a high care for mental, neurological, orders will rise over the next 15 are therefore not treated or their ages of trained personnel and mortality rate even and substance-use disorders years, with changing contribu- cases not reported. Those who diagnostic equipment. (MNS) disorders in the region. tory factors. It will be necessary are treated by traditional healers Analyzing epidemiological though it is a vaccine- Much attention has been fo- to track these changes. will not be reported. Even at data is also complicated. For preventable disease. cused on infectious disease in de- There was a consensus at the clinics, the number of deaths, PAGE 14 veloping countries since the is- meeting that there is most like- disabilities, and associated treat- See MNS Disorders • page 8 Alternate Cut-Off Might Boost Ultrasound Diagnostic Accuracy

BY KERRI WACHTER ported at the annual meeting of (Radiology 2003;229:340-6). curacy, none was more accurate ent carotid velocity threshold Elsevier Global Medical News the Society for Vascular Surgery. The criteria’s peak systolic ve- than the consensus criteria for numbers to define the severity The conclusions are based on locity (PSV) cut-off (more than this level of stenosis, said Dr. of carotid stenosis. However, BOSTON – Consensus criteria an analysis of the accuracy of 230 cm/sec) for detecting steno- Aburahma, professor of surgery there had been no standardiza- for the use of duplex ultrasound the consensus criteria for carotid sis of 70% and greater showed at West Virginia University in tion until the consensus criteria can be used accurately for the di- duplex ultrasound (CDUS), good sensitivity (99%) and speci- Charleston. However, the NPV in 2002. The consensus panel agnosis of stenosis of the inter- compared with angiography, of ficity (86%). Positive predictive of the consensus criteria for recommended that PSV should nal carotid artery that is 70% or 376 arteries in 197 patients. The value (PPV) was 93%, the nega- 50%-69% stenosis (PSV, 125-230 be the primary parameter. greater, but diagnostic accuracy consensus criteria were devel- tive predictive value (NPV) was cm/sec) was disappointing at In the study by Dr. Aburahma can be improved for 50%-69% oped by a multidisciplinary pan- 98%, and the overall accuracy 81%, he added. and his colleagues, arteries were stenosis by using other cut-off el to simplify the ultrasound di- was 95%. Although other cut-off Several classification systems values, Dr. Ali F. Aburahma re- agnosis of carotid artery disease values offered comparable ac- have been used, offering differ- See Ultrasound • page 4

Also in this issue of WORLD NEUROLOGY ... Efforts to contain the spread of Chagas disease in South and Central Amercia have paid off, but the disease is now an emerging problem in nonendemic countries because of migrations, writes Dr. Marco Oliveira Py. See Page 12 01_10wfn10_10.qxp 9/27/2010 12:01 PM Page 2

2 • WORLD NEUROLOGY WWW.WFNEUROLOGY.ORG • OCTOBER 2010

EDITOR IN CHIEF’S COLUMN Calendar of The Burden of International Events 2010 Neurological Disease Symposium on Neuroinflammation 63rd Annual Meeting of the and Neuroinfection American Academy of Neurology n the World Health Organization cine’s Forum on Neuroscience and Nov. 2 April 9-16 (WHO), Neurology is a footnote in Neurological Disorders about the Glasgow, Scotland Honolulu, Hawaii, USA Ithe Noncommunicable Diseases quality of care for mental, neurologi- www.rcpsg.ac.uk/Education/Events/ www.aan.com/go/am11 and Mental Health Divi- cal, and substance use Physicians/Pages/ed_spMedical sion. To a certain extent, (MNS) disorders in sub-Sa- Symposia.aspx 21st Meeting of the European the attention of the WHO haran Africa. The report Neurological Society is driven by consideration makes it clear that there 7th International Congress on May 28-31 of the DALY, the Disability are important needs in that Mental Dysfunctions and Other Non- Lisbon, Portugal Adjusted Life Year. Disor- region for dealing with Motor Features in Parkinson’s www.congrex.ch/ens2011 ders become important many noncommunicable Disease and Related Disorders based on premature loss of neurological disorders. Dec. 9-12 European Neuro-Ophthalmology life and disability. Epilepsy is one example of Barcelona, Spain Society Meeting In the grand scheme of a substantial problem www2.kenes.com/mdpd2010/ June 18-21 things, infectious disease is where more education as pages/home.aspx Barcelona, Spain still the biggest health BY MARK HALLETT, M.D. well as more therapy www.eunos2011barcelona.com/ problem worldwide. Low- would be valuable. 2011 er respiratory infections are number 1, Although neurological disorders are 4th European Neurological World Congress on Huntington diarrheal diseases are number 2, pegged as noncommunicable, there are Conference on Clinical Practices Disease HIV/AIDS is number 5, and neonatal many that are communicable. Two oth- Jan. 28-30 Sep. 11-14 infection, tuberculosis, and malaria er articles in the current issue illustrate Lisbon, Portugal Melbourne, Australia are 10, 11, and 12, respectively. this point. Chagas disease (p. 12) is en- www.paragon-conventions.net/enc- www.worldcongress-hd2011.org Noncommunicable disease is of less- demic in South America and should be cp2011/ er importance. Cerebrovascular dis- suspected in patients with autonomic 7th International Congress on ease at number 6 is the only neuro- nervous system abnormalities or stroke. 10th International Conference on Vascular Dementia logical condition in the top 20. It is Tetanus is still common in many de- Alzheimer’s & Parkinson’s Diseases Oct. 20-23 anticipated, however, that in the com- veloping countries, and this includes March 9-13 Riga, Latvia ing years, infections will be better con- Ethiopia (p. 15). The acute onset of se- Barcelona, Spain www2.kenes.com/vascular2011/ trolled, and noncommunicable dis- vere spasms and autonomic dysfunc- www.kenes.com/adpd pages/home.aspx eases will become more important. tion is dramatic. As described in the ar- Unipolar depression is predicted to be ticles, treatment for both these 3rd Asian and Oceanian Parkinson's 20th World Congress of Neurology number 1 by 2030. conditions is difficult, and the best ap- Disease and Movement Disorders Nov. 12-17 On page 1 of this issue of WORLD proach is prevention. It is good to hear Congress Marrakesh, Morocco NEUROLOGY, there is a report from the that progress is being made in public March 25-27 www2.kenes.com/wcn/Pages/ Uganda National Academy of Sci- heath for Chagas disease and in vacci- Taipei, Taiwan Home.aspx ences’ Forum on Health and Nutrition nation for tetanus, though there is still www.aopmc2011taiwan.com and the US-based Institute of Medi- a way to go. ■

GLOBAL MEDICAL RESEARCH ORLD Publisher Peter F. Bakker, W ELSEVIER GLOBAL MEDICAL NEWS A Division of International Medical News Group NEUROLOGY President IMNG Alan J. Imhoff Editor in Chief Mary Jo M. Dales WORLD FEDERATION OF NEUROLOGY WORLD NEUROLOGY, an official publication of the World Federation Executive Editors Denise Fulton, Kathy Scarbeck Editor in Chief Dr. Mark Hallett (USA) of Neurology, provides reports from the leadership of the WFN, its Managing Editor Renée Matthews EDITORIAL ADVISORY BOARD member societies, neurologists around the globe, and news from Clinical News Editor Jeff Evans Dr. Pierre Bill (South Africa); Dr. William M. Carroll (Australia); the cutting edge of clinical neurology. Content for WORLD NEUROLOGY Circulation Analyst Barbara Cavallaro Dr. Jagjit S. Chopra (India); Dr. Michael Finkel (USA); is provided by the World Federation of Neurology and Elsevier Global Executive Director, Operations Jim Chicca Dr. Osvaldo Fustinoni (Argentina); Dr. Francesc Graus (Spain); Medical News. Director, Production and Manufacturing Yvonne Evans Dr. Alla Guekht (Russia); Dr. Steven Ringel (USA); Production Manager Judi Sheffer Dr. Daniel Truong (USA); Dr. Alexandros Tselis (USA) Disclaimer: The ideas and opinions expressed in WORLD NEUROLOGY Creative Director Louise A. Koenig do not necessarily reflect those of the World Federation of Neurol- WFN OFFICERS ogy or the publisher. The World Federation of Neurology and Else- EDITORIAL OFFICE President: Dr. Vladimir Hachinski (Canada) 5635 Fishers Lane, Suite 6000 First Vice-President: Prof. Werner Hacke (Germany) vier Inc., will not assume responsibility for damages, loss, or claims Rockville, MD 20852 Secretary-Treasurer General: Dr. Raad Shakir (United Kingdom) of any kind arising from or related to the information contained in +1-240-221-4500 Fax: +1-240-221-2541 ELECTED TRUSTEES this publication, including any claims related to the products, drugs, US ADVERTISING Dr. Wolfgang Grisold (Austria); Dr. Ryuji Kaji (Japan); Dr. Gustavo or services mentioned herein. Rory Flanagan Roman (USA) 60 Columbia Rd., Building B Editorial Correspondence: Send editorial correspondence to Morristown, NJ 07960 EGIONAL IRECTORS R D WORLD NEUROLOGY, 5635 Fishers Lane, Suite 6000, +1-973-290-8222 Fax: +1-973-290-8250 Dr. Ahmed Khalifa (Pan Arab); Dr. Robert Griggs (North America); Rockville, MD 20852, U.S.A.; [email protected]; [email protected] Prof. Richard Hughes (Europe); Dr. Alfred K. Njamnshi (Pan Phone +1-800-798-1822 Classified Sales Manager, IMNG Africa); Dr. Ana Mercedes Robles de Hernandez (Latin America); Robert Zwick Dr. Amado San Luis (Asia-Oceania) Address Change: Fax change of address to +1-973-290-8245 +1-973-290-8250 Fax: +1-973-290-8250 EXECUTIVE DIRECTOR [email protected] Keith Newton POSTMASTER: Send change of address (with old mailing label) Classified Sales Representative nd World Federation of Neurology to WORLD NEUROLOGY, Circulation, 60 B, Columbia Rd., 2 Fl., Andrea LaMonica Hill House, Heron Square Morristown, NJ USA 07960 800-381-0569, Fax: 914-381-0573 Richmond, Surrey, TW9 1EP, UK [email protected] Tel: +44 (0) 208 439 9556/9557 Fax: +44 (0) 208 439 9499 WORLD NEUROLOGY, ISSN: 0899-9465, is published bimonthly by INTERNATIONAL ADVERTISING nd [email protected] Elsevier Inc., 60 B, Columbia Rd., 2 Fl., Morristown NJ 07960. Chris Woods Phone +1-973-290-8200; Fax: +1-973-290-8250. 32 Jamestown Road EDITOR OF THE JOURNAL OF THE NEUROLOGICAL SCIENCES Camden London NW1 7BY Dr. Robert Lisak (USA) ©Copyright 2010, by the World Federation of Neurology +44 207424 4454 [email protected] 01_10wfn10_10.qxp 9/23/2010 2:32 PM Page 3

OCTOBER 2010 • WWW.WFNEUROLOGY.ORG WORLD NEUROLOGY • 3

PRESIDENT’S COLUMN Planned Change: An Antidote to Obsolescence he new ad- cation, communication, and interaction need to do research. If we measure rological Sciences and the International ministration among our Committees, Task Forces, something we do, implement a change, Brain Research Organization. The event Thas commit- and Applied Research Groups. and measure the result, then we have drew participants from 14 sub- ted itself to conti- A Web Site and Communications Task done research. Not all the results will be Saharan countries – and resulted in our nuity and change. Force chaired by Werner Hacke (Ger- worthy of a journal article, but all results Ivory Coast colleagues joining the WFN. Our sound finan- many), Wolfgang Grisold (Austria), and are worth writing up and sharing. cial status despite Pete Engel (USA) brought proposals for “Research” has acquired the unfortu- The Asia Initiative BY VLADIMIR the recession; our improving the Web site at the WFN nate connotation of an elitist activity Ryuji Kaji (Japan), chair of this initiative, HACHINSKI, M.D. on-schedule plan- Council of Delegates meeting that took carried out in laboratories. The impor- reported (via Skype) on his investigation ning for the place during the European Federation of tant questions in medicine are those that of opportunities to improve and expand World Congress of Neurology in Mar- Neurological Societies in Geneva in Sep- matter to patients. In its broadest sense, neurological care in Asia, where most – rakesh, Morocco, (Nov. 12-17, 2011); and tember. The Web site will mark a new be- research is a method of finding answers, about 60% – of the world’s neurological our successful publications, the Journal of ginning for the way in which we interact whether in fundamental biology or in pa- patients live. He presented a list of possi- the Neurological Sciences and WORLD NEU- as a global community. It will be designed tient care. Philip Gorelick (USA), cochair ble members of Asia Initiative Executive. ROLOGY, are evidence of that continuity. and managed by a professional company, of the Applied Research Committee, has The change I refer to was first men- and will be interactive, flexible, modular, been charged with exploring how the The Latin America Initiative tioned in my candidate’s statement for and highly user friendly and accessible. WFN can encourage the application and Dr. Roman, chair of the Latin American the World Federation of Neurology Communication between the Com- evaluation of available knowledge. Initiative, reported on the distinguished President (April 2009, p. 1) and it is what mittee and Task Force members will be history of neurology in Latin America, I continue to advocate in my bimonthly enhanced by having conference calls set Membership the long and strong presence of the Latin columns in this publication. It was also up through the WFN Central Office There was an exploratory discussion at American branch in the WFN Neuro- reflected in the outcomes of discussions ([email protected]). Each Com- the retreat about our current system of epidemiology Research Group, and the at a planning retreat in London in June. mittee or Task Force will be required to “one society, one vote” and its effect on upcoming neuroepidemiology congress We began that meeting by exploring appoint a member to keep detailed min- issues such as the election of Officers and in Punta del Este, Uruguay (Nov. 29-Dec. what makes the WFN unique. We are utes of the conversations and the steps Trustees and the selection of sites for the 3, 2011). He said there were numerous the voice of neurology worldwide. The and actions arising from them. The World Congresses. opportunities for collaboration with oth- Federation comprises 110 member soci- WFN expects to receive brief trimonth- Some argue the impact of individual er societies. He also reported on plans for eties, which represent most of the ly reports of the activities of all Com- members of societies with thousands of next year’s Panamerican Congress of world’s neurologists and through them, mittees and Task Forces. members is devalued, compared with the Neurology in La Paz, Bolivia (March 5- the hundreds of millions of current and impact of a single neurologist of a five- 8). Our Latin American colleagues are to future neurological patients. Education member society. The counterargument explore the desirability of forming a Many new organizations have been Dr. Sergay and his Education Committee is that the WFN is a federation of soci- Panamerican Federation of Neurology. formed in recent years in response to the cochair, Dr. Grisold, presented a com- eties and not an organization of individ- proliferation of subspecialties, but the prehensive plan for developing a coher- ual neurologists. Reports on Neurological Diseases fact remains that most neurologists need ent accreditation of programs and certi- Several other international societies Dr. Diop presented highlights of his de- to be general neurologists, and the WFN fication of individuals and fellowships, have a balanced model, whereby the tailed and impressive World Health Or- is one organization that aims to integrate, and the possible facilitation of depart- largest society cannot have more than an ganization report on stroke and epilep- evaluate, prioritize, and apply general mental exchange programs. They noted upper limit – say, 4 votes – compared sy in Africa. He is planning to publish a neurological knowledge. We are setting that the plans will need support from an with the smallest society with 1 vote. similar document on neurology in gen- the standards for carrying out those aims office structure, a Web master, and an an- This complex issue, with practical and eral in Africa under the auspices of the and have created the Evaluation and Ac- nual budget based on its priorities. symbolic implications, is being addressed WFN and the Africa Initiative. creditation Task Force, chaired by Aksel by the Membership Committee, chaired Dr. Shakir presented data on neurolo- Siva (Turkey) and cochaired by Sarosh Ka- Applied Research by William Carroll (Australia) for con- gy in Arab countries from a forthcoming trak (India) and Charles Warlow (UK), to Donna Bergen, chair of the Applied Re- sideration by the Council of Delegates. article with a coauthor. The attendees evaluate teaching courses and congresses. search Committee, reported on her on- also discussed whether the WFN should The WFN’s endorsement of a course or going discussions with the WFN’s Re- The Africa Initiative produce comprehensive reports on neu- congress will mean that the activity has search Groups. Currently, 28 are listed, Alfred Njamnshi (Cameroon), chair of rology for all regions of the world. high quality and is practicable, identifying although 2 groups – Cerebrospinal Fluid the Africa Initiative, and Amadou Gallo it as an activity of value. and Neurorehabilitation – no longer ex- Diop (Senegal), presented a thoughtful, Criteria for Evaluation ist. The entities are referred to as re- systematic approach and plan. Their pri- Dr. Grisold presented a proposal for eval- Reformulation of the Mission search groups, which is a reflection of ority is the accreditation of training pro- uating projects for funding. He empha- Stephen Sergay (USA), chair of the WFN their origin, but their main activities grams on the continent. Some of these sized the need to implement a classic pro- Education Committee, spoke at the re- seemed to be more focused on education. programs have been in place for half a ject management approach that would treat about the importance of planning The participation of the Research century, in part because of the efforts of include prioritization, initiation, planning for the future. Groups in determining the scientific and pioneers such as Michel Dumas working and design, execution, control and mon- He noted that organizations generally educational programs of the biennial with our African colleagues. itoring, and closure and evaluation. progress by advancing along a series of World Congress of Neurology is a pri- Dr. Njamnshi highlighted the impor- steplike plateaux, but if an organization ority, and most have shown an interest in tance of financing priority activities on Financial Report does not plan its ascent to the next level, being more involved. The Applied Re- a continuous basis. The Africa Initiative Dr. Shakir presented the financial report. changing circumstances will render it in- search Committee was one of those that also met in Geneva last month. Although the Federation’s operating costs creasingly irrelevant. Planned change is met last month in Geneva to establish a Our colleagues in Cairo and elsewhere are modest and last year’s World Congress the antidote to obsolescence, he asserted. template of new mutually beneficial re- have offered to train neurologists for in Bangkok fared well financially, it is fac- His comments sparked an animated lationships between the Applied Re- sub-Saharan Africa. Secretary-Treasurer ing increasing costs in the planned invest- discussion that led to a reformulation of search Groups and the Committee. General Raad Shakir will go to Egypt to ment in the Web site and in supporting the the WFN’s mission: “To foster quality There will be a report back on that meet- sign a memorandum of understanding new initiatives. This reinforces our need to neurology and brain health worldwide.” ing in the December issue of WORLD on behalf of the WFN. focus our efforts in seeking partners and NEUROLOGY. Gustavo Roman (USA) reported on to begin fundraising for our projects. Web Site and Communications Findings from numerous studies have the success of the 3rd Regional Teaching The London retreat and last month’s An essential step in fulfilling the WFN shown that continuous medical educa- Course in Africa that was held in Abidjan, meeting in Geneva were important be- mission will be to upgrade and enhance tion has little impact on patient care un- Ivory Coast. He had represented the cause they signaled the beginning of a our Web site. It represents our public less it is linked to an audit, incentives, or WFN at the course, which was held joint- number of new initiatives and a new era face and can serve as a medium for edu- both. To implement what we know, we ly with the European Federation of Neu- for the WFN. ■ 01_10wfn10_10.qxp 9/23/2010 2:34 PM Page 4

4 • WORLD NEUROLOGY WWW.WFNEUROLOGY.ORG • OCTOBER 2010

NEUROLOGICAL HISTORY Foot Eponyms Leave Their Mark

BY PETER J. KOEHLER, without fanning of them, when the ex- M.D., PH.D. ternal inframalleolar skin area is irritat- ed, in cases of organic disease of the t the turn of the 19th century, the spino-cortical reflex paths. I shall call it neurological examination as we the external malleolar sign.” Aknow it today could already be rec- Chaddock was not aware of Yoshimu-

ognized. However, physicians worldwide OEHLER ra’s work. He believed his sign had ad-

continued searching for more signs to dif- J. K vantages over Babinski’s plantar reflex ferentiate between weakness resulting because dorsiflexion of the foot as with- from structural lesions of the central ner- ETER drawal reaction to painful stimuli oc- . P R

vous system and that caused by hysteria. D curred less often. He published on sev- For example, Joseph Babinski, who had de- eral other differences between his and scribed his Babinski-extensor sign in 1896, Babinski’s signs and sent the papers to OURTESY

went on to describe several more signs, in- C Babinski for comments. Babinski’s broth- cluding the trunk-thigh sign in 1897. er Henri (author of Gastronomie Pratique HOTOS

In the first decade of the 20th century, P under the pseudonym Ali-Bab), acting as two physicians, one working in Japan Charles Gilbert Chaddock (left) described the malleolar sign in 1911, unaware that his secretary, wrote to Chaddock: “My and the other in the United States, tried Kishaku Yoshimura had published on the same sign in a Japanese journal in 1906. brother ... has confirmed your observa- to find variant signs on the foot. In 1906, tions on the reflexes. He thinks your Kisaku Yoshimura described the external malleolus sign ese, which is probably why it remained largely unnoticed work is very interesting.” (Igaku Chuo Zasshi 1906;4:533-49; 824-41; 939-55). He until his compatriot, Kunio Tashiro, published it in Eng- Yoshimura and Chaddock’s signs were among some published (in Tokyo and Vienna) on another reflex, the lish (Arch. Neurol. 1986;43:1179-80). of the many reflexes and signs that are recognized in a Mendel dorsal foot reflex. But a 56-page article on the The American physician working on the same sign figure on the plantar muscle reflex in Robert Warten- lateral foot reflex was published in 1906 only in Japan- was Charles Gilbert Chaddock, professor of nervous and berg’s The Examination of Reflexes. A Simplification mental diseases at Marion-Sims College (Chicago: Year Book Publishers, 1945; first published as of Medicine – later the school of medi- papers in Archives of Neurology and Psychiatry in 1944). , cine at St. Louis (Mo., USA) University. Wartenberg had fled the Nazis in 1935 and settled in He had worked with Babinski in Paris San Francisco, where he tried to order, interpret, and sim-

ARTENBERG between 1897 and 1899 and had intro- plify the plethora of signs that had been published. The ., 176 ,W

NC duced the Babinski sign in the United names of neurologists from many different countries now ,I States on his return. distinguish the signs and reflexes associated with the foot:

EFLEXES Chaddock translated numerous Bechterew and Rossolimo (Russia); Guillain, Barré, R works and was author of Outlines of Sicard, and Cantaloube (France); Sternberg and Mendel UBLISHERS P Psychiatry (St. Louis: Commercial Print- (Germany); Markov (Poland), and Weingrow (USA).

OOK ing Company, 1904). However, after Obviously, the description of these reflexes and signs had B 1898, he published mainly on neuro- been an international occupation. ■ EAR

Y logical subjects, including three papers XAMINATION OF THE HE T ©E in 1911 on the malleolar sign, of which DR. KOEHLER is a neurologist in the department of Yoshimura and Chaddock’s signs were among the many depicted in he wrote, “I have found in extension of neurology at the Atrium Medical Centre, Heerlen, the Robert Wartenberg’s Examination of the Reflexes. A Simplification. one or more, or all, of the toes, with or Netherlands. Visit his Web site at www.neurohistory.nl.

curacy of 93% compared with 89% for the racy was 92% for stenosis of 50%-69%. Criteria Okay for 70% Stenosis consensus cut-off of 125 cm/sec. “Consensus criteria can be used accu- Ultrasound • from page 1 The standard values used up until the rately for the diagnosis of greater than or consensus criteria were developed were equal to 70% stenosis, but the accuracy evaluated with both CDUS and angiog- ter than the correlation for EDV or sys- a PSV of at least 120 cm/sec for less than can be improved in detecting 50%-69% raphy within a 30-day period. The per- tolic or diastolic ratios. 50% stenosis, PSV of at least 140 cm/sec stenosis if the [internal carotid artery] centage of stenosis was measured in ac- The researchers compared several PSV for at least 50% stenosis, and a PSV of at PSV is changed to 140 cm/sec to less than cordance with the NASCET (North cut-offs for diagnosing stenosis no greater least 150 cm/sec and an EDV of at least 230 cm/sec,” Dr. Aburahma concluded. American Symptomatic Carotid En- than 50% and found the most accurate 90 cm/sec for at least 70% stenosis. Disclosures: Dr. Aburahma reported darterectomy Trial) method. Peak sys- value was 137 cm/sec, with an overall ac- Using these cut-offs, the overall accu- that he had no relevant disclosures. ■ tolic velocity and end-diastolic velocity of the internal carotid artery were both measured during CDUS. r. Aburahma and his colleagues teries for 70%-99% stenosis (Stroke whether or not DUS as a single test is Patients were excluded if they had un- Dproposed an alternative duplex 2005;36:2105-9), illustrating the wide sufficient to estimate carotid artery dergone carotid artery endarterectomy or ultrasound (DUS) peak systolic ve- variability in DUS criteria. Factors stenosis reliably. In clinical practice, carotid artery stenting, or had a carotid locity (PSV) cut-off for a such as location- and oper- DUS may be a valuable first tool in artery dissection, flow-mediated dilation, 50%-69% stenosis that re- ator-dependency of DUS screening patients suspected of hav- or significant brachiocephalic stenosis. sulted in a significantly testing may in part explain ing carotid artery stenosis. If treat- The patients had a mean age of 68 higher diagnostic accura- this variability. ment is considered however, in my

years and 47% were men. Of these, 11% COMMENTARY cy. An important question Moreover, an earlier opinion, a second noninvasive test had normal carotid arteries, 30% had less is how the newly proposed meta-analysis reported a should be added, such as CT or MR than 50% stenosis, 23% had 50%-69% cut-off for a 50%-69% low diagnostic accuracy for angiography, to estimate the degree stenosis, 26% had 70%-99% stenosis, and stenosis performs in other DUS in general and for de- of stenosis reliably. 10% had total occlusion. Patients were patient populations. In the tecting a 50%-69% of also fairly evenly divided between symp- past, other groups have stenosis in particular PAUL J. NEDERKOORN, M.D., is a tomatic (53%) and asymptomatic. also suggested different PSV cut-offs (Lancet 2006;367:1503-12). neurologist and clinical epidemiologist In terms of Pearson correlation be- for various degrees of stenosis, such Therefore, the results of the study at Academic Medical Center, tween the consensus criteria and an- as 220 cm/sec for ipsilateral arteries by Dr. Aburahma and his coworkers Amsterdam. He has no relevant giography, the overall correlation was and 290 cm/sec for contralateral ar- raise the important question of disclosures. quite good for PSV cut-offs at 0.81 – bet- 01_10wfn10_10.qxp 9/23/2010 2:38 PM Page 5

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6 • WORLD NEUROLOGY WWW.WFNEUROLOGY.ORG • OCTOBER 2010

RESEARCH GROUP REPORT: MOTOR NEURON DISEASES Seeking Common Ground Across Spectra BY ALBERT LUDOLPH, M.D., A Global Perspective on Epidemiology mentia specialists, Parkinson specialists, Chair, WFN Motor Neuron Diseases We intend to work on the worldwide epi- and motoneuron specialists from China, Research Group demiology of ALS/MND. We recognize India, Africa, and South America. We plan ORLA HARDIMAN, MB BCH that ALS/MND has been carefully de- to discuss procedures with these colleagues Secretary scribed in the Western and industrialized during our symposium in December. Dr. Ludolph (left) is professor of neurology and world, but the epidemiological features of chair in the neurology department, University of Ulm, Germany. Dr. Hardiman is professor of neu- these diseases in developing countries Scrutinizing the El Escorial Criteria rology in the neurology department at Beaumont are less known. According to the estab- The WFN’s El Escorial Criteria for the di- Hospital and Trinity College Dublin, Ireland. lished studies in some developing coun- agnosis of ALS have served us well, but tries (Guadeloupe, New Guinea, and their practical use is sometimes confusing ecent research has shown that biological samples for modern tech- Guam), there may be a much closer link for general practitioners and laypersons. amyotrophic lateral sclerosis and niques such as proteomics, transcrip- among ALS, atypical parkinsonism, and Therefore, we have started working on Rfrontal temporal dementias par- tomics, and metabolomics is essential. frontal dementias than is the case in Eu- making these criteria more practical and tially form a spectrum of diseases and Under the auspices of our group, Prof. rope and North America. Conversely, the useful. We organized an initial meeting of share etiological, pathogenetic, and clin- Markus Otto of the University of Ulm, frequency of ALS in genetically admixed European experts in Frankfurt in No- ical features. In light of this, the World Germany, has convened a group of neu- countries such as Cuba seems to be con- vember 2009 to define the problems. The Federation of Neurology’s Motor Neu- rochemists, CSF specialists, and geneti- siderably lower. We are planning an ini- participants included the authors, along ron Diseases and Aphasia and Cognitive cists out of the FTD and ALS/motor tiative that will systematically study the with Wim Robberecht (Belgium); Disorders research groups have decided neuron diseases (MND) fields to compile epidemiology, clinical features, and nat- Leonard van den Berg (the Netherlands); to combine their respective interests. guidelines for preprocessing of samples. ural history of ALS, ALS/FTD, and Mamede de Carvalho (Portugal); Rein- This approach is timely, given the es- These guidelines will be published in ALS/Parkinson’s in developing countries. hard Dengler (Germany), and Adriano tablished relationship between the two Amyotrophic Lateral Sclerosis and Other Chio and Vincenzo Silani (Italy). Our spectra. We plan to collaborate with the Motor Neuron Disorders, the journal of the Redefining Through Education American colleagues have been informed frontal temporal dementias (FTD) group ALS/MND research group, which is edit- As a first step to redefine the clinical spec- of the initiative and we will further discuss by organizing educational programs to fa- ed by Prof. Orla Hardiman. We plan to trum of ALS/MND with regard to the re- the developments in late 2010. cilitate genetic studies of amyotrophic lat- organize a symposium during this year’s lation to atypical parkinsonism/frontal eral sclerosis (ALS) in FTD – in particular, international symposium on ALS/MND dementias, we will attempt to establish Support for the ALS Journal in developing countries. The research in Orlando, Fla., USA (Dec. 11-13), at teaching seminars with respected and not- Amyotrophic Lateral Sclerosis and Other groups also intend to organize a sympo- which we shall discuss the clinical appli- ed colleagues from developing countries. Motor Neuron Disorders, the ALS/MND sium during next year’s World Congress cations of these guidelines. We shall also This teaching will include epidemiological research group’s journal, is currently in of Neurology in Marrakesh, Morocco. discuss the implementation of biomark- features as well as the new findings on the a niche. In an effort to bolster the jour- ers into clinical trials in the ALS/MND molecular relations of ALS/MND to atyp- nal, we plan to team up with the Apha- Guidelines for Biologic Samples field; this is necessary because most clin- ical parkinsonism and frontal dementias. sia and Cognitive Disorders research In our field, we have learned that stan- ical trials of ALS/MND have been un- We are establishing a group of col- group to include articles on frontal tem- dardized and systematic preprocessing of successful. leagues comprised of epidemiologists, de- poral dementia whenever possible. ■ Plasma Beta-Amyloid Fluctuations Flag Cognitive Decline

BY MARY ANN MOON account for these discrepant results. Elsevier Global Medical News The investigators used data from a t is too early to recommend the vide an important window to the population-based study of aging to ex- Imeasurement of plasma Abeta for longitudinal course of the molecular hen plasma levels of beta-amyloid amine the link between plasma levels of diagnosis of AD or its prediction in mechanisms underlying AD. It could Wrise above normal and then de- the soluble oligomers Abeta-40 and -42 normal individuals. Multiple mea- help address why some individuals crease or stabilize in healthy elderly pa- and cognitive changes. A total of 880 surements of plasma Abeta over with high plasma levels of Abeta do tients, it signals the onset of a rapid de- nondemented participants provided one time, starting in the cognitively nor- not develop dementia, and whether cline in several cognitive domains, blood sample at baseline in 1999 and a mal state, are necessary to determine Abeta has a role in normal aging. It according to Stephanie A. Cosentino, second sample about 4.5 years later. the true longitudinal course of this could suggest the age at which inter- Ph.D., of the Taub Institute for Research They also underwent a battery of neu- COMMENTARY protein. These measurements should vention to reduce the production of in Alzheimer’s Disease and the Aging ropsychological tests at about 18-month arguably begin in middle age because Abeta-42 is likely to prevent AD. Brain, New York. intervals. the pathogenic processes in AD are In most patients, that decline takes During follow-up, 481 remained cog- likely to begin decades before symp- PERMINDER SACHDEV, M.D., PH.D., the form of Alzheimer’s disease. In the nitively healthy, 329 developed cognitive toms become manifest. If and when is a professor of neuropsychiatry at minority of patients who don’t develop or functional impairment but no de- certain limitations are overcome, se- the University of New South Wales, full-blown dementia, there is a marked mentia, and 70 developed AD. The co- rial plasma measurements might pro- Sydney. He has no disclosures. cognitive decline that primarily affects hort involved nearly equal percentages of memory rather than language or visu- Hispanics (37%), whites (31%), and ospatial domains, the authors wrote African Americans (31%). cognitive decline than other subjects. jects may be in the early stages of AD (Arch. Neurol. 2010 Aug. 9 [doi:10.1001/ “Overall, high initial levels of plasma An elevated level of Abeta-42 at base- but have not yet shown sufficient decline archneurol.2010.189]). Abeta-40 and Abeta-42, and stable or de- line predicted cognitive decline in mem- in nonmemory domains to meet the Some studies have shown a correla- creasing Abeta-42 at follow-up, were as- ory, language, and visuospatial domains, criteria for dementia. Alternatively, they tion between elevated plasma beta-amy- sociated with faster global cognitive de- with subjects in the highest quartile of may remain free of dementia due to bi- loid (Abeta) levels and development of cline regardless of dementia status,” the beta-amyloid level consistently declin- ological factors such as the ability to mild amnestic cognitive impairment or investigators wrote. ing significantly faster than subjects in clear high levels of beta-amyloid or psy- frank Alzheimer’s disease (AD) within a Subjects whose initial Abeta-40 and the lowest quartile. chosocial factors such as the presence of few years; others have found that de- Abeta-42 levels were in the top three However, in the subgroup of subjects cognitive reserve. creasing levels correlate with these cog- quartiles had significantly faster cognitive who remained cognitively unimpaired, Disclosures: The study was funded nitive declines. decline than did those in the lowest quar- those with high baseline levels of Abeta- by grants from the National Institutes of The findings the current study suggest tile. Those with either decreasing or sta- 42 showed declines only in the memory Health, Bethesda, Md., USA. The in- that the timing of the plasma sampling ble Abeta-42 levels at the second mea- domain. vestigators had no relevant disclosures and of the subjects’ disease stage might surement had significantly faster The authors suggested that these sub- to report. ■ 01_10wfn10_10.qxp 9/23/2010 2:41 PM Page 7 01_10wfn10_10.qxp 9/23/2010 2:42 PM Page 8

8 • WORLD NEUROLOGY WWW.WFNEUROLOGY.ORG • OCTOBER 2010

MEETING ROUND-UP WFN Holds Movement Disorders Course in Ukraine

BY YURIY MATVIYENKO, (the Netherlands); and Dr. Andrzej M.D., PH.D. Friedman (Poland) – as well as four lo- cal lecturers, Dr. Yanush Sanotsky, Dr. bout 100 neurologists and neu- Iryna Karaban, Dr. Tetiana Slobodin, rology residents from across and Dr. Sergiey Moskovko. The topics AUkraine attended a day-long they covered included cueing and au- course in movement disorders orga- tonomic dysfunction in PD, the nized by physicians from the Lviv Re- etiopathophysiology of idiopathic PD, gional Clinical Hospital, Lviv National genetics of PD, and current therapies, Medical University, and the World Fed- among others. eration of Neurology’s Parkinsonism Many of the attendees said they had and Related Disorders Research Group. found the course informative and useful The gathering marked the first time the for their clinical practice. They each re-

Federation has organized a meeting in ATVIYENKO ceived a copy of the textbook Parkinson- Ukraine. M ism Disease & Related Disorders by Erik The incidence of Parkinson’s disease URIY Wolters, Teus Van Laar, and Henk . Y R

(PD) in Ukraine is high. There are 1,800 D Berendse (Amsterdam: VU University persons in the database for the Lviv re- Press, 2008). gion alone, which has a total population For my part, I was honored to be a OURTESY

of 2.5 million people; and incidence is C member of the organizing committee about 85-95 patients per 100,000 persons Among the faculty of experts in parkinsonism and related disorders who for this event and I sincerely hope that of the general population of the country, participated in the movement disorders course were (from left) Lyudmyla the WFN Parkinsonism and Related based on data from noncontrolled epi- Fedoryshyn, Yanush Sanotsky, Zbigniew K. Wszolek, Tetiana Slobodin, Erik Ch. Disorders Research Group continues to demiologic investigations. However, Wolters, Andrzej Friedman, and Erwin van Wegen. support such courses in Ukraine. ■ there is almost no special training in movement disorders for general neurol- For these reasons, the event was im- parkinsonology by world experts in DR. MATVIYENKO is an assistant ogists, except for a certified course orga- portant for the attendees who had the the field – Dr. Zbigniew K. Wszolek professor in the department of neurology nized twice a year in Lviv by the region- opportunity to be updated on current from the United States; Prof. Dr. Erik at the Lviv National Medical University, al center of extrapyramidal disorders. diagnostic and therapeutic trends in Ch. Wolters and Dr. Erwin van Wegen Ukraine.

cific neurological tests with ap- accepted, and they have time to ask questions relating to their Integrated Approach Is Best propriate long-term supervi- spend with patients and engage records. More broadly, it could MNS Disorders • from page 1 sion. This would require that the whole family. There were ex- also provide epidemiological professional neurologists and amples of traditional healers data in real time. example, while we were in Ugan- ications interact badly with anti- psychiatrists reduce their prac- who had learned to comple- Development of these sys- da, we met a few children who retrovirals. This presents a dire tices and become public health ment Western forms of treat- tems is underway. For example, will be included in a study of pe- challenge given that in some re- leaders instead, and that there ment and to refer particular con- a Ghana-based nonprofit, with diatric neurological disorders to gions of Africa more than 20% be task-shifting to health care ditions to hospitals. We were support from pharmaceutical be funded by the US-based Na- of the population is infected workers who are trained for even told about a Ugandan companies, has established a tional Institutes of Health (NIH) with HIV. Terminology and lan- shorter periods of time in spe- chemotherapeutic laboratory mobile phone–based system and National Institute of Neuro- guage differences, and problems cific skills at all levels. It is in the that is analyzing the active in- called mPedigree that con- logical Disorders and Stroke with record-keeping also con- area of workforce management gredients of traditional reme- sumers in West Africa can use (NINDS). It was striking that the tribute to uncertainty in the data. that governmental policies dies while preserving intellectu- to verify whether a drug is gen- etiology in two out of five cases could be helpful – in formaliz- al property for the healers. uine or counterfeit by texting a seemed to be a high fever from a Trickle-Down Training ing the structure and providing However, others pointed out code to a central registry. previous unidentified infection, Participants at the meeting not- remuneration for community that there is no standard of care A joint Uganda National Acad- while a third disorder was pre- ed that we know how to treat health workers, resources, and among healers and that respect- emy of Sciences-IOM report, en- sent at birth. the common MNS disorders, as career paths for professionals. ful handling of the relationship titled “Mental, Neurological, and This underscores Dr. Donald overwhelming as that might be, can be challenging, particularly Substance Use Disorders in Sub- Silberberg’s observation that in but that the root of the problem The Community as a Resource when the traditional treatments Saharan Africa: Reducing the sub-Saharan Africa, the burden of lies with the severe shortage of Dr. Paul Farmer, a medical an- are harmful. Treatment Gap, Improving neurological disorders is related trained personnel and lack of thropologist and physician, has Quality of Care,” will soon be to the higher incidence of birth resources. noted that there are advantages Tapping In to Technology available from the NAS. The defects; mental retardation; cere- The MNS terminology reflects to community-based health care. Mobile phone technology al- NINDS has been funding re- bral palsy; bacterial, viral, and integration of neurological dis- In the sub-Saharan setting, these ready is widely used in Africa for search grants in Africa under the parasitic infections; epilepsy; and ciplines but, given the intercon- would include an opportunity banking and might also be use- trans-NIH Brain Disorders in the head and spinal cord trauma nectedness of MNS disorders to address the social causes of ful as a tool for both providers Developing World program in from traffic accidents than in with other diseases and trauma, MNS disorders, the mutual re- and patients. Radio, television, Uganda, Zambia, Malawi, and more developed countries (Soc. it makes sense for treatment, pa- inforcement of treatment and and CDs allow for one-way ed- Tunisia. The institute will also Psychiatry Psychiatr. Epidemiol. tient education, and referrals to prevention, and improved ad- ucation efforts, but mobile cofund a hypertension and 2010;45:487-95). be integrated with primary care herence to treatment regimens. phone technology would allow stroke project in Zimbabwe Furthermore, in instances in as well. Not only would that kind The meeting participants for a one-to-one interaction be- through the Medical Education which the neurological conse- of coordination leverage trained were divided on the involve- tween health workers in the field Partnership Initiative, which quences of HIV/AIDS, malaria, personnel and resources, but it ment of traditional healers, as who need to use diagnostic or built on the PEPFAR effort. ■ and tuberculosis are diagnosed, would also better serve the ma- distinct from trained communi- treatment algorithms and a cen- treatment can still be complicat- jority of people, who mostly live ty health workers, in the deliv- tralized expert or system. The DR. MARINO is a scientific ed. Dr. Angela Kakooza-Mwe- in villages and must walk long ery of treatment. In support of technology could be used for re- information analyst and special sige, a neurologist from Mak- distances to clinics. their involvement, some partic- minding or informing patients assistant to the director at the erere University School of Several participants proposed ipants said that traditional heal- about treatment follow-ups, test National Institute of Neurological Medicine, Kampala, explained training more community ers know the village where they results, medication availability, Disorders and Stroke in Bethesda, that standard antiepileptic med- health workers to carry out spe- practice, they are accessible and clinic hours, or to allow them to Md., USA. 01_10wfn10_10.qxp 9/23/2010 2:47 PM Page 9

Before the researcharch is published...

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R EADE THE LEADER IN NEWS AND MEETING Clinical Neurology News COVERAGE — We Write Medicine’s First Draft —

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10 • WORLD NEUROLOGY WWW.WFNEUROLOGY.ORG • OCTOBER 2010 Ruling Puts US Embryonic Stem Cell Research in Limbo Researchers stress the importance of having access studied to see which type is the best, within the strict ethical guidelines set to all possibilities to help advance their work. forth by the National Academy of Sci- Judicial Ping-Pong ences. Using all of the possibilities, sci- BY MARY ELLEN SCHNEIDER families suffering from fatal and chronic entists will be able to learn about devel- Ǡ Aug. 23. A US federal judge Elsevier Global Medical News diseases and disorders.” opment and disease and as well as repair hands down a ruling that bars the Evangelos Kiskinis, Ph.D., of the Har- damage from trauma, aging, and dis- use of federal funds for any re- ome researchers studying human vard Stem Cell Institute, said that it ease,” Dr. Redmond asserted. search involving human embryonic embryonic stem cells in the Unit- was important to remember that many There is also concern about privately stem cells. Sed States are surprised, disap- of the recent advances in stem cell re- funded labs becoming isolated. As a result of the temporary in- pointed, and even angry about the legal search were a direct result of re- “Although certain labs are increasing- junction, the US NIH stops accept- back-and-forth over the federal govern- searchers having access to embryonic ly relying on private funding for em- ing submissions of information on ment policy on funding research using stem cells. “Milestone advances such as bryonic stem cell research and therefore human embryonic stem cell lines the cells (see Box, top right). the generation of induced pluripotent are less affected than those that are for review and suspends all review Last year, President Obama greatly stem [iPS] cells, a promising, novel tech- mainly NIH funded, major advances in of embryonic stem cell lines. expanded opportunities to receive federal nology to ‘make’ embryonic stem-like the field are more likely if [there are] Ǡ Aug. 31. The US Justice Depart- funding for embryonic stem cell research cells, would never have been achieved more labs. One or two isolated, pri- ment asks for a stay of the lower court’s injunction. Eligible and The argument for Researchers Ǡ Sep. 9. The Justice Department ineligible the two scientists couldn’t have is granted a temporary administra- activities will need ‘shows the generated iPS tive stay by the US Court of Ap- to be isolated to judge’s lack of cells if they peals for the District of Columbia ensure NIH funds understanding of hadn’t known Circuit. don’t support the funding about embryonic Ǡ Sept. 20. The date by which nonsanctioned process.’ stem cells. both parties to the suit had to pre- research. sent information to the court. DR. KRIEGSTEIN DR. REDMOND DR. KISKINIS

when he issued an executive order that without knowing what we do about vately funded labs are never going to [be opens the door for every scientist who eliminated many of the restrictions the properties of embryonic stem cells able to answer] major questions such as ever has a grant request rejected on the placed on funding during the George W. [and] they are also continuously relying ‘what causes neurodegeneration in merits to sue the federal government,” Bush administration. The US National on research with embryonic stem cells ALS?’ These are issues that the research the American Society for Reproductive Institutes of Health in Bethesda, Md., fol- for improvement and eventual clinical community has to be able to pursue un- Medicine said in a statement condemn- lowed with guidelines that allowed re- application,” he said. affected as a whole,” said Dr. Kiskinis. ing the court decision. search to be conducted on embryonic Even institutions with deep pockets Another source of concern for re- Dr. Redmond added that the argu- stem cells derived from embryos created are concerned that private funding searchers has to do with the legal issues ment for standing for the two scientists through in vitro fertilization and donat- alone is not enough. “It’s a blow to us,” involved in the case. An earlier lawsuit was a “terrible” precedent and that it ed for research. said B.D. Colen, a spokesman for the challenging the Obama stem cell guide- “shows the judge’s lack of understanding But with the current uncertainty, Harvard Stem Cell Institute. “It’s a blow lines had been dismissed after the court of the funding process.” some researchers worry that the devel- to the field.” ruled that the plaintiffs had no standing In granting the temporary injunction, opment of therapies that use embryonic Dr. D. Eugene Redmond, Jr., profes- to challenge it. Judge Royce C. Lamberth, the chief stem cells will be set back and that the sor of psychiatry and neurosurgery and However, the recent injunction came judge in the US District Court for the Dis- loss of federal funding will have a chill- director of neural transplantation and about after the court decided that two trict of Columbia, said the NIH guide- ing effect on newly minted researchers repair, Yale (Conn.) University School of researchers who work with adult stem lines violated the intent of Congress to who are considering whether to enter Medicine, USA, commented that his cells could challenge the guidelines be- bar the use of federal funds for research the field. human embryonic stem cell research “is cause funding of embryonic stem cell in which human embryos are destroyed. The US-based Coalition for the Ad- funded by the forward-looking state of research was harming their chances for He said that the rules violated the vancement of Medical Research, which Connecticut and therefore not subject receiving federal funds for adult stem Dickey-Wicker amendment, a rider gen- advocates for stem cell funding, called to this federal funding decision. But it is cells. erally attached to health spending bills the original injunction a “blow to the important that this ruling is overturned. This move was not well received by each year. It prohibits the use of feder- hopes of millions of patients and their “Stem cells, of all types should be those involved in research. “This judge al funds for the creation of a human em- bryo or embryos for research purposes or research in which a human embryo tem cell science has had to navi- ate effects of the injunction because to ensure that inclusion of investiga- or embryos are destroyed or discarded. Sgate a complex ethical and politi- relatively few of the human embry- tors working with embryonic stem However, the Obama administration cal landscape ever since human em- onic stem cell projects here are NIH cells does not jeopardize continued has argued that the amendment doesn’t bryonic stem cells were first created funded. Most of [us] are funded by funding. apply because federal funds are used for in the lab. Over the past 9 years, and the California Institute of Regenera- Research progress in science is un- research on the embryonic stem cell lines, over two administrations, federal tive Medicine (CIRM) for the work predictable. But progress most cer- not in the destruction of the embryos. funding was available for this research we do using human embryonic stem tainly cannot be made without a pol- Judge Lamberth did not find the argu- subject to specific restrictions based cells. We have newly constructed icy that ensures sustained funding. ment persuasive. “[Embryonic stem cell] COMMENTARY on ethical considerations. Within this stem cell laboratories that were paid The US Congress should act to clari- research is clearly research in which an em- awkward framework, the science has for by philanthropic donations and fy its real intent concerning the pursuit bryo is destroyed,” he wrote in the order. advanced, but the recent injunction CIRM grants, where stem cell re- of human embryonic stem cell re- “Despite defendants’ attempt to separate would countermand all the previous search, including work with human search, rather than let policy be held the derivation of [embryonic stem cells] policies and put a full stop to federal embryonic stem cells, can proceed hostage by the whim of an individual from research on the [embryonic stem support for human embryonic stem regardless of the twists and turns of judge. cells], the two cannot be separate.” ■ cell research. NIH policy. The impact on the field of stem A bigger impact will be the burden ARNOLD R. KRIEGSTEIN, M.D., To share your comments on this ruling on cell research is enormous and pro- of isolating our eligible and ineligi- PH.D., is the John G. Bowes stem cells, write to us at worldneurology foundly discouraging, not only to ble activities to ensure that NIH Distinguished Professor in Stem Cell @elsevier.com. If you are in a country scientists and students, but most of funds for allowable research do not and Tissue Biology and director of the outside of the United States, are there all to patients who have staked their spill over to support nonsanctioned Eli and Edythe Broad Center of similar rulings on or debates around the hopes on the promise of stem cell re- research. We may also need to scru- Regeneration Medicine and Stem Cell use of human embryonic stem cells in search. At [my institution], we are tinize all our multi-investigator NIH Research at the University of research? If not, how do your policies differ partially shielded from the immedi- grants including our training grants California–San Francisco. from those in the United States, and what are the implications for researchers? 11_16wfn10_10.qxp 9/23/2010 3:15 PM Page 11

OCTOBER 2010 • WWW.WFNEUROLOGY.ORG WORLD NEUROLOGY • 11 Study Backs Alteplase Within 4.5 Hours of Stroke

BY DIANA MAHONEY The extended time window was not as- within 3 months in the current investi- comes was still low in the cohort treat- Elsevier Global Medical News sociated with an increase in admission-to- gation occurred at significantly higher ed within 3-4.5 hours and the statistical treatment time. For patients registered rates in patients treated within 3-4.5 significance can probably be explained by xtending the time window for giv- both before and after 2008, the median ad- hours than in those treated within the the large sample size” and that the risks ing the recombinant tissue plas- mission-to-treatment time was 65 min- shorter time window. Functional out- of these outcomes were outweighed by Eminogen activator alteplase to is- utes, suggesting “the widening of the comes at 3 months after adjustment for the benefits of the treatment. chemic stroke patients has increased the time window has not resulted in delayed confounding variables also were worse in Disclosures: Some of the authors dis- percentage of patients who are eligible treatment of patients,” the authors wrote. those who received alteplase during the closed receiving grants or financial com- to receive the thrombolytic therapy with- As was the case in the earlier SITS- additional 1.5 hours of time. But Dr. pensation from Boehringer Ingelheim, out causing treatment delays, according ISTR observational study, symptomatic Wahlgren and his colleagues wrote that Ferrer, Thrombogenics, Sanofi-Aventis, to an analysis of two databases. intracerebral hemorrhage and mortality “the overall proportion of these out- Novo Nordisk, Paion, and Lilly. ■ Until recently, the use of alteplase, which has been shown to decrease the in- cidence of stroke-related disability, was recommended for use within 3 hours of the onset of acute ischemic stroke symp- Books and journals toms. In the fall of 2008, however, the European Stroke Organization, the American Heart Association, and the with a American Stroke Association began rec- global perspective ommending that the alteplase treatment time window be expanded to within 4.5

'%%. '%%. '%%+ Hardback/960 pages Hardback/432 pages Hardback/2672 pages THE EXTENDED TIME WINDOW ISBN: 9780443104077 ISBN: 9781416061854 ISBN: 9780323033657

DID NOT RESULT IN A RISE IN BUY ONLINE TODAY AT: BUY ONLINE TODAY AT: BUY ONLINE TODAY AT: ADMISSION-TO-TREATMENT TIME, elsevierhealth.com elsevierhealth.com elsevierhealth.com BUT REMAINED AT THE PRE-2008 LEVEL OF 65 MINUTES.

hours after stroke onset. The recom- mendation was based on findings from the European Acute Stroke Study III (ECASS III) and the International Stroke Thrombolysis Registry (SITS-ISTR), which both demonstrated the safety and efficacy of the broader treatment para- meter, wrote Dr. Nils Wahlgren of Karolinska University Hospital in Stock- holm, Sweden, and colleagues (Lancet Neurol. 2010;9:866-74). The researchers conducted a follow-up safety analysis using data from SITS- “...it should be found on the shelf of “Clear, literate, well organized, “It is unlikely that anyone caring ISTR. They sought to confirm or refute every neonatal department or unit.” and able to convey maximum for children with neurological whether patients receiving late alteplase International Journal of Adolescent Medicine and Health information...” disorders can or should practice treatment (between 3 and 4.5 hours) had Neurology (Review of the previous edition) without it.” an increased risk of intracerebral hem- JAMA 2006 orrhage and death within 3 months – a possibility that was reported in the initial ™ >cXajYZhdkZg-%%^bV\ZhVcYa^cZYgVl^c\hi]Vi ™ I]dgdj\]XdkZgV\Z[dgZVX]cZjgdad\^XVaY^hZVhZ ™ >ihXa^c^XVa[dXjh!Vadc\l^i]gZaZkVcihX^ZcXZ! SITS-ISTR study. XVeijgZi]ZaViZhi^ckZhi^\Vi^kZiZX]c^fjZh XaZVganYZÒcZhV\ZVidchZi!XdjghZd[^aacZhh! i]gdj\]dji^hY^gZXiZYViWdi]i]ZZmeZg^ZcXZY Of 23,942 patients included in SITS- ™ @Zned^ciWdmZhe^X`djii]Zbdhi^bedgiVci Xa^c^XVa[ZVijgZh!VcYigZVibZcidei^dch Xa^c^X^VcVcYi]Ze]nh^X^Vc^cigV^c^c\ ISTR between December 2002 and Feb- ^c[dgbVi^dc[dgi]ZWjhnheZX^Va^hi ruary 2010, 2,376 were treated with al- teplase between 3 and 4.5 hours after symptom onset. “The proportion of patients treated in The European Journal of Paediatric Neurology, a multi-disciplinary journal the 3-4.5 hour time window was twice as under the guidance of a prestigious International editorial board, publishes exciting clinical and experimental research in this rapidly expanding field. high in the last quarter of 2008 and three High quality papers written by leading experts encompass all the major times higher during the last quarter of diseases including epilepsy, movement disorders, neuromuscular disorders, 2009, compared with the first three-quar- neurodegenerative disorders and mental retardation ters in 2008. The number of patients treat- ed within 3 hours also increased,” the au- ZahZk^Zg#Xdb$Z_ec thors wrote. “Therefore, not only did the The Lancet Neurology is a lively monthly journal of original research, review, opinion, and news covering international issues relevant to neurologists publications seem to encourage partici- worldwide. With the leading Impact Factor of 14.4 in the field of clinical pating SITS physicians to offer treatment neurology, The Lancet Neurology publishes original research articles that to patients beyond the 3-hour window, but advocate change in, or illuminate, neurological clinical practice also they might have encouraged treat- ment with intravenous alteplase within i]ZaVcXZi#Xdb$cZjgdad\n the already accepted treatment criteria.” The support for the extended time window by the various stroke associa- tions might also have contributed to its rapid acceptance, they noted. 11_16wfn10_10.qxp 9/23/2010 3:16 PM Page 12

12 • WORLD NEUROLOGY WWW.WFNEUROLOGY.ORG • OCTOBER 2010 Chagas Disease Presents Long-Term Challenges merican trypanosomiasis, or Cha- iopathology of this late symptomatic gas disease, was first described in phase is not entirely clear, an autoim- ABrazilian rural areas in 1909 by mune mechanism is most probable Carlos Chagas, who noticed the rela- (Brain Pathol. 1997;7:599-611). tionship between occurrence of the dis- Chagas disease is endemic to Central ease and the prevalence the barber bee- and South America, where the World tle (or kissing bug), an insect in the Health Organization estimates 16 to 18 Reduviidae family. million people are infected. Vectorial trans- mission is the leading cause of the dis- BY MARCO OLIVEIRA PY, ease, though blood-product transfu- M.D., PH.D. sion and mother-to-baby transmission CDC is possible. Oral transmission is rare. Dr. Py is the coordina- Since the 1980s, the incidence of tor of the neuro-ICU of Chagas disease has been declining in MAGES COURTESY the University Hospital Brazil, Chile, and Uruguay. In 2003, I of the Federal Univer- Brazil was considered free of new cas- The barber beetle or kissing bug (left), is a vector for Chagas disease. It sucks sity of Rio de Janeiro, es of the disease (World Health Organ. blood from humans and eliminates feces containing the Trypanosoma cruzi Brazil. Tech. Rep. Ser. 2002;905:1-109), but parasite (right), which penetrates broken skin and enters the blood vessels. there are still some cases of oral trans- Chagas isolated the responsible para- mission. Transmission through blood the disease (Rev. Soc. Bras. Med. Trop. modynamics or cognitive domains. (Low site (Trypanosoma cruzi) from a Reduvi- transfusion is rare in South American 2004;37:376-83). There have been reports educational levels hampered interpreta- idae insect bowel. Then, working with countries because of mandatory testing of sympathetic and parasympathetic cell tion of the neuropsychological tests.) We Oswaldo Cruz, he isolated the same par- for the disease. However, Central and destruction, although a direct vagus nerve suggested parasympathetic dysfunction asite from the blood of a child with the lesion could not be demonstrated (Trans. in chronic chagasic patients is associated disease and of a cat from the same house R. Soc. Trop. Med. Hyg. 2000;94:405-8). with brain white matter lesions. We spec- as the child, and was thus able to describe Autonomic disturbances may cause these ulated that even in early stages, the disease the entire cycle of that new disease. arrhythmias and cardiomyopathy. Apart could promote an imbalance between The Reduviidae insects live in the from autonomic fibers, the peripheral ner- sympathetic and parasympathetic sys- cracked walls of houses where living vous system can also be affected, although tems, resulting in an unstable cardiac conditions are poor. They suck victims’ that is rare and is generally characterized rhythm (J. Neuroimaging 2009;19:332-6). blood, and at the same time eliminate fe- as a mild sensitive-motor polyneuropathy. In another study, we found no correla- Y ces that contain the parasite, which in P Alencar described cerebral and cere- tion between the presence of serum func- turn penetrates broken human skin and bellar atrophy without any inflamma- tional circulating antibodies with beta- LIVEIRA

enters the blood vessels (Mem. Inst. Os- O tion in the central nervous system (J. adrenergic or muscarinic activity and the waldo Cruz 1909;1:159-218). Bras. Neurol. 1982;18:7-12). Although autonomic system function or the pres- Few patients present with the acute ARCO some still dispute the existence of direct ence of white matter hyperintense lesions . M R

form of the disease in the first 10-60 days D central nervous system lesions, Chagas (seen in MRI) in chronic chagasic patients after infestation. This acute form is char- disease is strongly associated with car- (Arq. Neuropsiquiatr. 2009;67:633-8). The acterized by fever, eyelid and face edema, dioembolic strokes (Arq. Neuropsiquiatr. mechanism of the pathobiology of the OURTESY

conjunctivitis, and in some cases lym- C 1984;42:105-15) and other stroke mecha- genesis of hyperintense lesions is still un- phadenomegaly, hepatosplenomegaly, A brain MRI in a patient diagnosed with nisms (J. Neurol. Neurosurg. Psychiatry resolved, although apparently related to and anasarca. Most patients (66%-99%) re- chronic Chagas disease shows white 2003;74:516-8), with some authors sug- parasympathetic dysfunction. main asymptomatic during this period, matter hyperintense lesions. gesting an association between try- but a severe and often fatal form of the panosome infection and stroke even in The Clinical and Public Health Route disease that includes acute myocarditis or South America will have Chagas disease the absence of cardiomyopathy or cardiac The practitioner neurologist should al- encephalitis might occur in about 10% of patients for at least a few more decades be- arrhythmias (Stroke 2005;36:2015-7). ways be aware of the possibility of Cha- symptomatic patients, mostly in infants or cause of the disease’s long latent period. Ǡ Cognitive function. Data on cognitive gas disease in a patient with unexplained immunosuppressed individuals (Rev. Inst. function in Chagas disease are scarce. strokes and/or autonomic nervous system Med. Trop. São Paulo 1993;35:111-6). Lingering Symptoms Some authors have reported worse results dysfunction, especially if the patient has A chronic asymptomatic but serolog- Ǡ Neurological disorders. These occur in the Mini-Mental State Examination, returned from an endemic area or has re- ically positive phase usually follows. This from the early phase of Chagas disease. Wechsler Memory Scale, and Wechsler ceived blood products, even decades ago. phase lasts 10-30 years until cardiac or di- Complex cardiac arrhythmias may be ver- Adult Intelligent Scale in Chagas disease The disease is diagnosed through sensitive, gestive symptoms arise in 20%-40% of ified by 24-hour Holter and ergometric patients, compared with controls (Arq. specific serological testing using im- infected subjects. Although the phys- tests and get worse with progression of Neuropsiquiatr. 1994;52:200-3). Others munofluorescence and hemagglutination. have reported neurophysiological dys- Specific treatment for Chagas disease is function as revealed by the EEG (P300 po- underused because of the delay in the di- tential) in these patients, which could in- agnosis most of the time. Use of try- directly be related to cognitive impairment panocidal drugs, such as benznidazole, in (Arq. Neuropsiquiatr. 2000;58:262-71). the disease’s acute phase can be reason- Ǡ Parasympathetic disorders. My col- ably safe and effective, although more ef- leagues and I have shown that Chagas dis- fective drugs for Chagas disease are scarce. ease patients – even in the early stages and For most patients diagnosed in the chron- without cardiac dysfunction – present ic phase, the only treatment is the control signs of a parasympathetic disorder that of the consequences of the disease, such correlates significantly with brain sub- as treating cardiac arrhythmias and heart cortical white matter abnormalities. This failure to prevent embolic strokes. was shown by an inverse and significant Prevention is the best management for correlation between reduced cardiac fre- Chagas disease. Eradication of the vector, quency variability (evaluated by the res- better living conditions in rural areas, and piratory sinus arrhythmia test) and the mandatory testing of donor blood have presence and number of hyperintense le- been effective. But the disease is now an sions in brain white matter seen in MRI. emerging problem in nonendemic coun-

CDC In all, 52% of our patients showed hy- tries because of migrations. Rigid control perintensities in MRI, compared with of blood donors could be useful in those about 13% in the general population. But countries as well, where serological tests OURTESY ■ C there was no correlation with cerebral he- for the disease should be mandatory. 11_16wfn10_10.qxp 9/23/2010 3:17 PM Page 13 11_16wfn10_10.qxp 9/23/2010 3:18 PM Page 14

14 • WORLD NEUROLOGY WWW.WFNEUROLOGY.ORG • OCTOBER 2010 Tetanus Weighs on Neurological Burden in Ethiopia BY YOHANNES W. WOLDEAMANUEL, M.D., AND All of the patients were treated with for tetanus per 100,000 inhabitants in ANHAR HASSAN, MB BCH tetanus antitoxin, intravenous antibiotics Ethiopia and the rest of sub-Saharan Dr. Woldeamanuel (left) is in the depart- (ceftriaxone 1 g IV b.i.d., metronidazole Africa is 200-750, compared with rates ment of neurology at Addis Ababa Univer- 500 mg IV t.i.d.), antispasmodics (chlor- of less than 10 in North America (14). sity Medical Faculty in Ethiopia. promazine 12.5 mg IV q.i.d., diazepam Thus, tetanus continues to contribute a 5 mg IV p.r.n.), adrenergic blockers (pro- significant neurological burden to Dr. Hassan (right) is in the department of pranolol 10 mg PO b.i.d.), and general Ethiopia, even though it is vaccine pre- neurology at the Mayo Clinic in Rochester, supportive measures. ventable. Minn., USA. Two of the patients showed progres- sive improvement, were transferred to Conclusion Background southern Ethiopia revealed the missed the general ward, and were discharged Tetanus is a vaccine-preventable disease. The burden of neurological disease is opportunity for tetanus immunization in 2 weeks later. The other two patients Completing vaccination schedules and high in Ethiopian hospitals (1). Neuro- pregnant women during antenatal care died, with sudden cardiac death sec- increasing awareness of the importance logical admissions account for a signif- to be 11.6% (10). ondary to severe dysautonomia. The of seeking medical care for tetanus- icant proportion of medical admissions In this article, we report on recent ob- survivors received tetanus toxoid be- prone wounds are important in decreas- – up to 18% in one study. Findings servations of patients admitted with fore discharge. ing the high incidence, morbidity, and have shown that both infectious and tetanus, and highlight the preventable as- mortality of this disease. ■ noninfectious etiologies are responsible pects of this disease. Discussion (2). Among the neuroinfectious dis- Diagnosis of tetanus is largely clinical, References eases seen, vaccine-preventable neuro- Methods and is made by exclusion of other 1. Murray, CJL; Lopez, AD. The Global logical disorders include rabies, po- We reviewed the number of patients spasm-causing diseases such as strych- Burden of Disease. Geneva: World liomyelitis, and tetanus, all of which with tetanus admitted to the intensive nine poisoning, acute dystonic reac- Health Organization, 1996. tions, seizures, tetany, and stiff-person 2. Neurology 2007;68:338-42. syndrome (11). The possible factors 3. Dire, DJ. Tetanus. In: eMedicine Spe- that predisposed our patients to tetanus cialties, Emergency Medicine, Infec- were not being vaccinated, a recent tious Diseases [online]. Available at penetrating tetanus-prone wound, and www.emedicine.medscape.com. Ac- failure to present for initial first aid. cessed April 30, 2010. Short incubation period and onset time, 4. MMWR CDC Surveill. Summ. with complications of dysautonomia in 1998;47:1-13. an underserviced ICU, likely result in 5. West Afr. J. Medicine 2003;22:150-1. higher mortality at an earlier period of 6. BMJ 2003;326:117-8. admission. 7. Neurology India 2002;50:398-407. Tetanus cases have high morbidity 8. Cvjetanovic, B. Public Health Aspects and mortality. A study of generalized of Tetanus Control. In: Veronesi, R, RGANIZATION

O tetanus cases from six hospitals in Addis ed. Tetanus: Important New Con- Ababa showed that none of the patients cepts. Amsterdam: Excerpta Medica,

EALTH were immunized. The study included 55 1981:1-7. H patients (39 men, 16 women) with a 9. Heavens, A. Health Workers Reach ORLD

W mean age of 30 years. The mean incu- Remote Villagers in Ethiopia With bation period was 11.9 days (range 1-90 Tetanus Vaccine. In: UNICEF Ethiopia days), and the mean onset time was 38 [online], www.unicef.org/infoby- OURTESY

C hours (1-9 hours). country/ethiopia_37790.html. Ac- Ethiopia has not seen the significant decline in the incidence of tetanus that comes The patients in the study were treat- cessed April 30, 2010. with improved DTP3 coverage, as shown in this graph based on global data. ed with TAT, antibiotics, and sedatives, 10. Ethiop. J. Health Development and only three of them received tetanus 2000;14:143-8. are associated with high morbidity and care unit (ICU) at Addis Ababa Univer- toxoid before discharge. Death occurred 11. Bleck, TP; Brauner, JS. Tetanus. In: mortality. sity’s Tikur Anbessa Hospital during Feb- in 27% of the patients, and was corre- Scheld, WM, et al., eds. Infections of Tetanus cases are rarely seen in de- ruary and March 2010. lated with shorter incubation and inva- the Central Nervous System, 3rd ed. veloped countries. In the United States, Four patients with tetanus (three men sion periods, as well as with abdominal New York: Lippincott, Williams & the annual incidence rate of tetanus has and a teenaged girl) were admitted dur- rigidity, tachycardia, sweating, and fluc- Wilkins, 2004:625-48. dropped from 600 in the 1940s to less ing that time (see table). All of them had tuating blood pressure, the researchers 12. East Afr. Med. J. 1990;67:887-93. than 100 in 2005. The average annual in- had severe generalized tetanus. Their reported (12). Another hospital chart 13. Ethiop. Med. J. 2009;47:291-7. cidence was 0.15 per million between mean age was 22.8 years (range 13-30 review from Gondar, Ethiopia, showed 14. Mathers, CD, et al. Global Burden of 1997 and 2001. This decline is a result of years), mean incubation period was 8.3 a higher mortality rate of 41.4% (13). Disease in 2002: Data Sources, Meth- widespread tetanus immunization (3,4). days (2-18 days), and average onset time The World Health Organization has ods and Results. www.who.int/ In contrast, the annual incidence of was 21.1 days (12-24 days). The patients’ reported that the age-standardized dis- healthinfo/paper54.pdf. Accessed tetanus worldwide is about 1 million, mean ICU stay was 19.5 days (2-41 days). ability-adjusted life year (DALY) rate April 30, 2010. with the disease occurring mostly in developing countries. One study in a Nigerian hospi- Characteristics of Four ICU Patients With Severe Generalized Tetanus tal showed that tetanus is the second most common reason Case Age (yrs.)/ Injury type/ Vaccination Incubation Onset time ICU (days) Complications Outcome sex location (days) for neurological admission (5,6,7). A report in 1981 showed 1 13/F Thorn/left calf None 2 1 day 32 Aspiration pneumonia, Improved the mortality rate from tetanus dysautonomia, deep to be 28 per 100,000 in Africa, venous thrombosis compared with less than 0.1 per 2 20/M Fall/right knee Unknown 18 1 day 41 Aspiration pneumonia, Improved dysautonomia EWS 100,000 in North America (8). N Because of the low vaccina- 3 30/M Nail/right sole Unknown 4 12 hours 2 Dysautonomia, cardiac Died

tion rates and home deliveries arrest EDICAL M that take place in unsanitary 4 28/M Nail/right sole Unknown 9 1 day 3 Dysautonomia Died

conditions, Ethiopia has one of LOBAL the highest neonatal tetanus G morbidity and mortality rates Source: Dr. Woldeamanuel LSEVIER

in the world (9). A study in E 11_16wfn10_10.qxp 9/23/2010 3:18 PM Page 15

OCTOBER 2010 • WWW.WFNEUROLOGY.ORG WORLD NEUROLOGY • 15

Dr. Piotr Jachimczak replies: LETTER TO THE EDITOR A report on the phase IIb study AP TALK BACK 12009-G004 has been accepted for pub- lication in the peer-reviewed journal Misleading Information McDonald criteria) at 14 months and Neuro-Oncology. The Dr. Wick and Dr. We’d Like to An article on trabedersen for treating also the secondary end point, overall Weller are correct in stating that the Hear From You malignant glioma contained mislead- survival. control group was treated with TMZ or ing information on the efficacy of this Progression-free survival at 14 PCV. However, they are incorrect on Do you have an idea for a story? drug (“Trabedersen Bests Standard months is a novel and not a prespecified two essential points. Do you want to comment on Chemotherapy for High-Grade end point. It was never disclosed how First, the primary end point of the tri- something you’ve read recently ORLD EUROLOGY Gliomas,” W N , June the decision matured to look at this end al was “tumor control rate at 6 months” in WORLD NEUROLOGY? 2010, p. 3). point. The survival data are likely in- and not “tumor response;” and second, Trabedersen is an antisense oligonu- fluenced by salvage therapies that need we presented at the American Associa- Or perhaps you’d like us to cleotide to TGF-beta2 that is being ex- to be carefully analyzed. tion of Cancer Research “tumor pro- share news of your research or amined for safety and efficacy in malig- The article provided no new data and gression rate at 14 months” and not an upcoming event with the nant glioma. The above-mentioned implied efficacy that awaits confirma- “progression-free survival.” global neurology community ... article suggested to report positive results tion. In addition, the reference to the The tumor progression rate at 14 of the previous trials or new information subgroup of younger glioblastoma pa- months was 16.7% for patients treated Write to us at about the compound. Neither is correct. tients is difficult to appreciate because with trabedersen and 58.3% for patients [email protected] Data from the phase IIb trial AP none of the data have undergone peer treated with chemotherapy (P = .0032). or send a fax to 12009-G004 in recurrent or refractory review. Moreover, the ongoing trial is In addition, tumor progression rate was +1-240-221-2541. high-grade glioma (anaplastic astrocy- not further pursuing this subgroup, but a prespecified secondary end point of toma/glioblastoma multiforme) have focusing on anaplastic astrocytoma the trial. For Letters to the Editor, please in- been repeatedly presented at meetings only. Why? The phase IIb trial was mainly con- clude your name and address, af- but await full publication. Part peer-reviewed publications on ducted to elaborate on the most effec- filiation, and conflicts of interest in Looking into the available data, the the clinical efficacy data include a re- tive dose of trabedersen – one of the regard to the topic discussed when trial was negative for the primary end view (Expert. Rev. Anticancer Ther. common tasks of phase II trials. The in- you write to us. Letters may be edit- point, that is, tumor response in the co- 2009;9:1663-74) and some very prelim- tegration of a control group should ed for space and clarity. hort of 145 patients in comparison with inary efficacy evaluations from the lead to a valid clinical trend. Significant standard chemotherapy – temozolo- phase I trial (Oligonucleotides 2007; efficacy data are then required from mide (TMZ) or procarbazine/lomus- 17:201-12). TGF-beta2 is undoubtedly a phase III trials for regulatory approval. in glioblastoma patients is currently tine [or CCNU]/ vincristine (PCV); not promising target for malignant gliomas. The phase IIb results clearly showed planned. vincristine alone as stated in the article. However, more care and prudence are that patients with anaplastic astrocy- The sponsor of these studies, Anti- The lead investigators reported a advisable when reporting on new agents toma and glioblastoma multiforme have sense Pharma, is a small, solely venture- promising signal in the subgroup of 39 in diseases with a prognosis as dismal as a different prognosis. Therefore, we de- capital–financed company, and the de- anaplastic astrocytoma patients (27 of glioblastoma. cided to investigate the efficacy of velopment of trabedersen has to be which were treated with the study com- Wolfgang Wick, M.D. trabedersen in two different trials. realized step by step. ■ pound and 12 with chemotherapy) for University Clinic, Heidelberg, Germany, A phase III trial in anaplastic astrocy- tumor control (complete or partial re- and Michael Weller, M.D. toma patients has started. A separate DR. JACHIMCZAK is senior scientific sponse or stable disease according to the University Hospital Zurich study to proof efficacy of trabedersen adviser at Antisense Pharma. B Vitamins Fail to Cut Vascular Events

aily supplementation with B vitamins was no bet- cidence of nonfatal stroke, nonfatal myocardial infarc- According to results of a fasting blood test at the end Dter than was placebo in preventing recurrent stroke tion, and death attributable to vascular causes as sec- of follow-up in 1,164 patients, B vitamin supplemen- and other major vascular events in patients who sus- ondary prevention in patients with a recent stroke or tation achieved a significant reduction in total homo- tained recent stroke or transient ischemic attacks. transient ischemic attack. cysteine, compared with placebo (difference, 3.8 micro- Investigators in the first placebo-controlled trial of B The randomized, double-blind, placebo-controlled mol/L; P less than .0001), but this did not seem to trans- vitamins in this population re- trial assigned 8,164 patients in 20 late into prevention of major vascular events. ported that major vascular events countries between Nov. 19, 1998, The authors noted that the study had several limita- occurred in 15% of patients as- B VITAMIN SUPPLEMENTATION and Dec. 13, 2008, to daily sup- tions, including incomplete adherence to trial design signed to daily B vitamin supple- plementation with B vitamins (2 and incomplete follow-up. The median duration of ad- SIGNIFICANTLY REDUCED TOTAL mentation, compared with 17% mg folic acid, 25 mg vitamin B6, herence to treatment was 2.8 years and the median du- of those assigned to placebo. HOMOCYSTEINE, BUT DIDN’T and 0.5 mg vitamin B12) or ration of follow-up was 3.4 years, which might not have “These results do not support the matching placebo. All of the pa- been long enough to identify or exclude any long-term use of B vitamins to prevent re- TRANSLATE INTO PREVENTION OF tients had experienced a stroke effects of B vitamin supplementation. current stroke,” they wrote VASCULAR EVENTS. or transient ischemic event in Results of a planned meta-analysis of individual data (Lancet Neurol. 2010;9:855-65). the previous 7 months. from previous trials of B vitamins as well as results of However, Prof. Graeme Han- three ongoing, randomized, controlled trials of B vit- key, from the Royal Perth Hospital in Australia and prin- Strong on Safety, Weak on Benefits amins might shed more light on the long-term effects cipal investigator of the VITATOPS (Vitamins to Pre- Baseline demographic and disease characteristics were of B vitamins as prevention of stroke and other major vent Stroke) study, qualified this statement in an e-mail similar between the groups. Of the total, 42% of pa- vascular events among the patient population studied interview. tients were white; 24%, east or southeast Asian; 26%, in VITATOPS, they said. “It is possible that we have reported a false-negative south Asian, and 7% were listed as “other” (numbers Disclosures: The study was funded by health and result, and that the [trial] was underpowered statistically rounded). At the time of randomization, 76% of pa- medical research councils in Australia, the United King- to reliably identify a clinically important treatment ef- tients were functionally independent. dom, and Singapore, the Australia National Heart fect, such as the one observed [that is, 9% relative risk Although daily B vitamin supplementation was safe, Foundation, Royal Perth Hospital Medical Research reduction and 1.56% absolute risk reduction over a me- it provided no benefit over placebo for the composite Foundation, and Health Department of Western Aus- dian of 3.4 years of follow-up],” he said. “If such a treat- primary end point of nonfatal stroke, nonfatal my- tralia. Dr. Hankey disclosed that he has received pay- ment effect is confirmed in ongoing trials, then B vita- ocardial infarction, and death attributable to vascular ments for serving on committees or as an adviser from mins would present a widely accessible, affordable, safe, causes (15% and 17%, respectively). Looking at those drug companies that are conducting trials on stroke pre- and effective addition to the current armamentarium end points separately, B vitamin supplementation did vention drugs, including Boehringer Ingelheim, John- of secondary prevention strategies for patients with not achieve a significant reduction in the risk of non- son & Johnson, Pfizer Australia, Sanofi-Aventis, and transient ischemic attack and stroke.” fatal or fatal stroke, nonfatal or fatal myocardial in- Schering-Plough. The investigators wanted to test the hypothesis that farction, or death from any cause; however, it was as- —Alice Goodman daily B vitamin supplementation would lower total ho- sociated with a significant reduction in death from mocysteine levels and thereby reduce the combined in- vascular causes (P = .04). Ms. Goodman is a freelance writer for LANCET NEUROLOGY. 11_16wfn10_10.qxp 9/23/2010 3:18 PM Page 16 WCN 2011_WORLD_CONGRESS_NEUROLOGY_kings_Size.ai 1 2010/07/22 5:35 PM