Neurosonology WFN Teaching Course in Tbilisi, Georgia

Meeting promotes ultrasonic techniques and research

By Marina Alpaidze, MD, PhD

Participants of the second Regional NSRG WFN meeting. From left to right: Marina Alpaidze, MD, President of NSRG WFN Georgian Chapter and President of Georgian Society of Neurosonology and Cerebral Hemodynamics; Alexander Razumovsky, PhD, FAHA, Secretary of NSRG WFN (U.S.); Natan Bornstein, MD, PhD, Vice-President of World Stroke Organization, President of European Society for Neurosonology and Cerebral Hemodynamics (Israel); and Ekaterina Titianova, MD, PhD, Dsc, President of Bulgarian Society of Neurosonology and Cerebral Hemodynamics.

The Neurosonology Research Group (NSRG) WFN is dedicated to the promotion of science and research as well of education and training in the field of ultrasonic techniques and its clinical utilization. Therefore, international cooperation and the dissemination of scientific information within the field of neurosciences and neurosonology is part of NSRG WFN activities.

During Oct. 25-26, 2014, the Georgian Chapter of the NSRG WFN successfully conducted the second NSRG WFN Regional Meeting in Tbilisi, Georgia. There were also participants from neighboring countries — Armenia and Azerbaijan. This two-day course was designed for individuals who are interested to perform and interpret neurosonology studies. The faculty discussed current status of neurosonology and some specific clinical applications; part of the meeting was dedicated to the hands-on practice. The lectures were delivered by well-known neurologists and neurosonology experts such as N. Bornstein (Israel), E. Titianova (Bulgaria), Z. Nadareishvili (U.S.), M. Alpaidze (Georgia), and A. Razumovsky (U.S.).

This second Georgian meeting was guided and directed under the auspices of the NSRG of the WFN and accredited by Tbilisi Medical University Continuing Medical Education (CME) Board for 10 CME hours.

Dr. Alpaidze is the Head of Ultrasound Laboratory, DEKA Medical Centre, University Clinic Department of Neurology, Tbilsi, Georgia.

With Limited Neurology Resources Worldwide, Translation and Implementation of Research Results Crucial for Global Health

BY Donald Silberberg, MD

Donald H. Silberberg

As I approach my third year as editor-in-chief of World Neurology, I wish to thank the many individuals who have helped to achieve our successful conversion from print to online format. The support and contributions of the officers and trustees of the World Federation of Neurology, the editorial advisory board, and Keith Newton’s assistance as assistant editor have been critical. Additionally, I wish to acknowledge the expert help by Rhonda Wickham and her associates at Ascend Integrated Media who have helped to unravel the process of online publishing and compose attractive pages. Their role is no less critical. Perhaps most importantly, the quality of original articles, book reviews, reports, and photographs has been superb, and I thank all authors and photographers. World Neurology’s future success will depend directly on your continuing contributions. If you are hesitant about the appropriateness of a submission, please contact me to discuss how to proceed.

In his President’s Report in this issue, Raad Shakir outlined the many important organizational advances that took place in 2014, including the development and strengthening of many regional neurological associations in conjunction with the WFN. This strengthening will be an important element in addressing one of the biggest problems that neurology must deal with — the resources that are available to provide clinical care and conduct needed research are wholly inadequate in many countries and regions.

Recognition that neurological disorders account for a very high proportion of all illness has been slow in coming. Even though the data that quantifies the global burden of nervous system disorders is still quite incomplete, it is clear that the disorders that are in the domain of neurology constitute a very large proportion of all illness globally. We must use the available epidemiology as we continue to advocate for the allocation of sufficient resources for the prevention, clinical care, and research that are clearly warranted by the data.

Fortunately, we are witnessing remarkable progress in research on almost every front. In addition to neuroscience itself, advances in genetics, immunology, microbiology, robotics, stem cell research, and many other fields will yield new therapies at an accelerating pace in 2015 and beyond. The initiation of national programs such as The Brain Initiative (U.S.), the Human Brain Project (European Union), and Japan’s Brain/MINDS project reflect national commitments to bring research, primarily brain mapping at this point, to levels that will lead to understanding the biological basis of nervous system disorders.

Many organizations are looking for ways to improve implementation, to bring clinical and laboratory research to all populations, whether in wealthy or low and middle-income countries. The phrase of the moment is “translational research,” originally used to describe bringing the fruits of laboratory research to the bedside. Neurologists must be active participants in the translation into practice by designing safe and credible clinical trials and working to make new therapies available to all who need them.

In my editorial in December, I introduced the use of “translational research” to also describe instances in which the results of epidemiologic research lead to the development of new public policy. Again, some neurologists will be in a position to help make this happen. Another relatively recently coined term is “implementation science” — dealing with questions such as why do established programs lose effectiveness over time, and how can multiple interventions be effectively packaged to increase cost effectiveness? Again, we as neurologists can both contribute to the science with our own research, and do more with the resources that are available.

You will think of many other examples of unmet challenges and opportunities, and I invite your comments, articles, and/or letters to the editor.

Apparent Death and Coma in the 18th Century

Curious Practices Arise from Fear of Being Buried Alive

Figure 1. Title page of the History and Memories of the Society for the Rescue of Drowned Persons (1780).

by Peter J. Koehler

Coma has been a phenomenon of interest for physicians as well as lay people through the ages and was associated chiefly with stroke (“apoplexy”) and trauma¹. One chapter in the history of coma has two extraordinary perspectives, notably coma following drowning and the fear of being buried alive, which played a role particularly during the late 18th century.

Drowning Rescue and Resuscitation

A considerable number of books on comatose persons, usually drowning victims, often referred to in the titles as “apparently dead,” appeared during the 18th century. These books were published when the first societies for the resuscitation of drowning people had been established. It is of no surprise that the first of these societies was founded in the Netherlands (1767), notably the Amsterdam Society for the Rescue of Drowning Persons (Maatschappij tot Redding van Drenkelingen). Due to the many canals, drowning was a frequent event in Holland. The society paid premiums for saved drowning persons and thus in the 1780 publication (Fig. 1), it is reported that “73 premiums had been distributed to good and indefatigable surgeons and other persons” in the years 1778-9. The lifesavers could choose between six gold ducats or a gold medal.

Figure 2. English translation of the Amsterdam Society by Thomas Cogan (1773).

Drowning persons were supposed to be brought inside a house, airways inspected, wet clothes removed, warmed up by rubbing with woollen clothes, and administered tobacco smoke fumigation by rectum. Following this warming up, bleeding could be applied from the arm or neck, but not too superfluous. Only if signs of swallowing acts were observed, not earlier, some hard liquor could be poured down in the mouth and the rapid spirit of ammonia salt kept under the nose. If this did not work, the drowning person should be laid in a preheated bed, accompanied by a naked person who provided natural heat. The book contains short histories of failed resuscitations and longer cases histories of successful ones.

A case history (March 27, 1778, 10;30 a.m., Noordwaddingsveen): a 5-year old boy, Jan van Someren, was missed for half an hour and found in the water, apparently dead, by his parents Cornelis van Someren and Aagje Joosten Robberts. A surgeon, Pieter de Nick, was sent for, the child brought inside and warmed up. The usual resuscitation methods were applied and only after a prolonged period (one hour) the blue lips disappeared and he began to cry. He was laid in a warm bed with another person and after some time he started to speak. He recovered completely the next day and Pieter de Nick received the gold medal.

Figure 3. American Society (Boston, 1788).

The Dutch example was soon followed by several other countries. In 1774, the English society was founded by physicians William Hawes and Thomas Cogan, the latter becoming interested after a visit to Amsterdam (Fig. 2). An American society was founded in 1787, notably The Institution of the Humane Society of the Commonwealth of Massachusetts (Fig. 3)^2-5. Although John Hunter (1776) suggested cessation of respiration was the primary cause of death and cardiac arrest secondary, and also wrote about ventilation, it would be more than a century before it was routinely applied (see also⁶).

Buried Alive

Next to coma in drowning persons, there was another aspect of apparently dead, notably a great fear for being buried alive, a.o. appearing from the titles of the publications, for instance, the book The uncertainty of the signs of death, and the danger of precipitate interments and dissections … with proper directions, both for preventing such accidents, and repairing the misfortunes brought upon the constitution by them. The book contains chapter titles such as: “A woman, falling into a syncope, occasioned by a violent fit of passion, suppos’d to be dead, and put into a coffin” and “Precautions to be us’d in order to recover those who have been drown’d or buried alive” (Figs. 4 and 5)⁷. Another example is the French Lettres sur la certitude des signes de la mort. Oà¹ l’on rassure les Citoyens de la crainte d’àªtres enterrés vivans (Fig. 6)⁸.

Figure 4. The Uncertainty of the Sign of Death (1746).

The English physician John Fothergill suggested that in some situations it might be profitable to “distend the lungs with air,” in particular in “sudden Deaths from some invisible Cause; Apoplexies, Fits of various Kinds, as Hysterics, Syncope’s, and many other Disorders, wherein, without any obvious Prae-indisposition, Persons in a Moment sink down and expire” (Fig. 7)⁹. Next to artificial ventilation, the use of electric shock, not unexpected in this age of medical electricity, was recommended¹⁰.

Figure 5. Fear of being buried alive (1746).

The fear of being buried alive led to curious practices including the one advised by the English lawyer and philosopher Jeremy Bentham to nail a wooden pin through the brain or heart for the prevention of interment of apparently dead (“require that a spike of appointed length, kept for the purpose, be run either through the heart, or into the brain, through the secket of the eye”) (Fig. 8)¹¹. The Danish-born French anatomist Jacob Winslow wrote a thesis about the uncertainties of the signs of death (translated and augmented by Jacques-Jean Bruhier), which contains stories of persons, who were buried almost too early. Huston was critical about Winslow’s and Bruhier’s “fabulous stories of recovery”¹². Winslow himself would have escaped a premature burial two times and concluded that putrefaction is the only real sign of death¹³. He referred to the well-known (but controversial) case, autopsied by the 16th century physician and anatomist Andreas Vesalius, who appeared to be alive, after which Vesalius was prosecuted for murder¹². The king of Spain changed the sentence into a voyage to the Holy Land.

Figure 6. French book on Certainty of Signs of Death by Louis (1752).

Later, even Charles Dickens was concerned about the apparent dead, as can be read in a contribution in his weekly journal, in which he warned against prematurely buried persons while still alive¹⁴. Coma, in drowning persons as well as the fear of being buried in such condition was an issue among physicians as well as lay persons for centuries in many countries.

Dr. Koehler is neurologist at Atrium Medical Centre, Heerlen, The Netherlands. Visit his website at www.neurohistory.nl.

This article was adapted from a section of Koehler PJ. The history of coma. In: Boes CJ (ed.). The History of Certain Disorders of the Nervous System. American Academy of Neurology, Philadelphia, 2014.

References

Koehler PJ, Wijdicks EFM. Historical study of coma: looking back through medical and neurological texts. Brain 2008;131:877-889
Historie en gedenkschriften van de maatschappij tot redding van drenkelingen. Amsterdam, Meijer, 1768.
Johnson A. A short account of a society at Amsterdam instituted in the year 1767 for the recovery of drowned persons with observations shewing that the utility and advantage that would accrue tot Great Britain from a similar institution etc. London, John Nource et al., 1778.
Figure 7. John Fothergill’s publication (1744).
Hawes W. The transactions of the Royal Human Society. London, Nichols, 1796.
The Institution of the Humane Society of the Commonwealth of Massachusetts: With the Rules for Regulating Said Society, and the Methods of Treatment to be Used with Persons Apparently Dead: With a Number of Recent Cases Proving the Happy Effects Thereof. Boston, 1788.
Payne JP. On the resuscitation of the apparently dead. Ann R Coll Surg Engl. 1969;45:98–107
The uncertainty of the signs of death, and the danger of precipitate interments and dissections…with proper directions, both for preventing such accidents, and repairing the misfortunes brought upon the constitution by them. London, Cooper, 1746.
Louis M. Lettres sur la certitude des signes de la mort. Oà¹ l’on rassure les Citoyens de la crainte d’àªtres enterrés vivans. Paris, Lambert, 1752.
Fothergill J. Observations on a Case Published in the last Volume of the Medical Essays, &c. “of recovering a Man dead in Appearance, by distending the Lungs with Air. Printed at Edinburgh, 1744” in The Works of John Fothergill, M. D . . . London, 1784. [Ed. J. C. Lettsom]
Figure 8. Jeremy Bentham, English philosopher and jurist.
Kite, C. An Essay on the Recovery of the Apparently Dead. London, Dilly, 1788.
Bentham J. Works vol. 6. Edinburgh, Tait, 1843, p.571.
Huston KG. Resuscitation. An historical perspective. Wood Library – Museum, Park Ridge, Illinois, 1976, p.2.
Winslow JB. Dissertation sur l’incertitude des signes de la mort et l’abus des enterremens, & embaumens précipités. Transl and commented by Bruhier JJ. Paris, Morel et al. 1742.
Dickens, C. “Apparent Death” in All the Year Round, New Series, Vol.II, No. 31 (Saturday, July 3, 1869), pp. 109-114.

ASAPP Combats Global Epidemic of Stroke

Organization Conducts Screenings in Uganda, India

Stroke is the third leading cause of premature death and disability worldwide. The burden of stroke is growing in low and middle-income countries due to many factors including population growth and aging, urbanization, unhealthy diets, physical inactivity and smoking. More importantly, these demographic and epidemiologic factors are driving a rise in the prevalence of high blood pressure, the leading independent risk factor for both ischemic and hemorrhagic stroke. In many less developed countries, particularly in rural areas, awareness of high blood pressure is extremely low and screening services are non-existent. On the other hand, treatment for high blood pressure is widely available and relatively inexpensive.

Figures 1. and 2. Dr. Jerome Chin and volunteers at an ASAPP project site in India in November 2014.

Since 2010, Dr. Jerome Chin, a neurologist in the U.S., has been volunteering for two months annually as an attending physician on the neurology ward at Mulago Hospital, the national referral hospital of Uganda in the capital Kampala. The neurology ward admits more than 50 acute stroke patients monthly, the majority with severe previously undiagnosed high blood pressure. In October 2011, Dr. Chin founded the Alliance for Stroke Awareness and Prevention Project (ASAPP) in Kampala to reduce the incidence of stroke in Uganda. ASAPP volunteers, who are mostly medical and other health professions students, provide free community-based screening and counseling for high blood pressure every week at places of religious worship. Individuals with elevated blood pressures are advised to make dietary and lifestyle changes and are referred for medical treatment if indicated. In December 2012, Dr. Chin visited the neurology ward at the All India Institute of Medical Sciences (AIIMS) in the capital Delhi. Similar to Mulago Hospital in Uganda, the majority of patients admitted to AIIMS with acute stroke have severe previously undiagnosed or untreated high blood pressure. In December 2013, Dr. Chin launched ASAPP in India.

ASAPP currently supports six project sites in Uganda and three projects sites in India. In addition, ASAPP is partnering with the Uganda Ministry of Health and other organizations including Rotary International and Impact India Foundation to provide free high blood pressure screening and counseling at special health camps and events. ASAPP project sites have provided more than 55,000 free screenings for high blood pressure since 2011. In the next few years, ASAPP plans to launch additional project sites in Uganda and India and expand to Nepal and other less developed countries. ASAPP is a U.S. tax-exempt non-profit charitable organization. For more information, visit www.asapp.org.

Report of the Membership Committee

By Jacques L. De Reuck

The Membership Committee of the World Federation of Neurology (WFN) will make a special effort during the coming years to attract neurologists of different countries who have difficulties to become part of the WFN, in particular from Africa.

For those countries that do not yet have a national neurological society, we propose to individual neurologists to apply first for Associated Membership, so that they can become familiar with the WFN and later apply for a full membership when they are able to form a national neurological society.

This proposal is not restricted to African neurologists. In order to overcome existing language barriers, we will accept proposals in French or Spanish, that will be translated into English when submitted to the WFN Board and Council of Delegates at the next congress in Santiago, Chile.

Contact the chair of the Membership Committee with additional questions and remarks at dereuck.j@gmail.com.

We hope that you will join us, so that the WFN will become more representative and able to stress the importance of neurological diseases in the World Health Organization.

De Reuck is the chairperson of the Membership Committee.

Fifth Congress of the European Academy of Pediatric Societies

By Nino Gogatishvili

With the support of World Federation of Neurology I attended the Fifth Congress of the European Academy of Pediatric Societies Oct. 17-21 in Barcelona.

The organizing societies were the European Academy of Pediatrics (EAP), The European Society of Pediatric and Neonatal Intensive Care (ESPNIC) and The European Society for Pediatric Research (ESPR).

The excellent organization of the congress made it possible for pediatric professionals from around the world to gain unparalleled access to the best scientific research programs. The scientific program was varied. Abstract topics included: primary care and general pediatrics, neonatology, neonatal brain and development, neonatal pulmonology, neonatal cardiovascular, neonatal nutrition and gastroenterology, neonatal infection, adolescent health, pediatric surgery, cardiology and cardiac surgery, gastroenterology and hepatology/nutrition, neurology and developmental pediatrics, pulmonology/allergy/immunology/asthma, intensive care and pediatric emergency care medicine, hematology and oncology, nephrology, infectious diseases, endocrinology/diabetes/metabolism and pharmacology.

My poster, PO-0834, “Long-Term Developmental Outcome of Children Prenatally Exposed To Antiepileptic Drugs” was presented on Oct. 19. My abstract also was published: N.Gogatishvili, T.Ediberidze, G Lomidze, N Tatishvili, S Kasradze. Arch Dis Child 2014; 99:Suppl 2 A526 doi: 10.1136/archdischild-2014-307384.1466

I am grateful for the support of World Federation of Neurology that permitted me to attend this important congress and obtain experience that will help me in my work.

Gogatishvili is with the Institute of Neurology and Neuropsychology, Tbilisi, Tbilisi State Medical University, Tbilisi, Georgia.

NSRG Teaching Courses in Latin America

Figure 1. Participants of the NSRG Course in Lima

By Prof. Dr. Med. Manfred Kaps

The Latin American Chapter of the NSRG organized teaching courses in Lima, Peru, and Mendoza, Argentina, in October. According to the NSRG teaching concept to offer a high level of theoretical knowledge and sufficient practical skills, both two-day courses included lectures and at least 50 percent practical training in small groups of no more than seven participants.

Figure 2. Mendoza in October 2014.

The strictly limited number of participants allowed individual mentoring and exchange among all participants and proved functional. At the closing ceremony when the local course directors Prof. Ana Valentia, Dra. Sylvia Cocorullo and Prof. Manfred Kaps as NSRG delegate delivered the participation certificates, there was lots of cheer and enthusiasm.

Figure 3. Participants of the NSRG Course in Lima.

The next NSRG accredited courses will take place in 2015 in Mexico, Brazil and of course during the XXII World Congress of the WFN in Santiago, Chile.

Kaps is professor of neurology at Justus-Liebig-University in Giessen, Germany.

MS: The First MENACTRIMS Congress

By Bassem I. Yamout, MD, FAAN

The First Congress of The Middle East North Africa Committee for Treatment and Research in Multiple Sclerosis (MENACTRIMS) was held Oct. 17-18 in Dubai. MENACTRIMS is an independent organization that facilitates communication and creates synergies among clinicians and scientists to promote and enhance research and improve clinical outcomes in multiple sclerosis (MS) in the Middle East and North Africa regions.

It was founded on Dec. 8, 2012, by nine eminent neurologists: Saeed Bohlega and Mohamad Jumaa from KSA, Riad Goueider from Tunisia, Raed Roughani from Kuwait, Maurice Dahdale from Jordan, Jihad Inshasi from the Emirates, Saher Hashem from Egypt, Issa Alsharuqui from Bahrain, and me from Lebanon. The prevalence of MS has been steadily increasing over the last few decades in the Middle East/North Africa region, reaching as high as 80/100,000 in some countries. The challenges posed by such a medical burden created the need for an official regional scientific committee to address all emerging issues related to MS in this region of the world.

The First MENACTRIMS Congress was the first major endeavor of the newborn MENACTRIMS organization, and with more than 500 attendees, including new practitioners as well as experienced MS specialists from all over the Middle East, North Africa and neighboring countries, it turned out to be the largest scientific MS event in the region’s history. Speeches were given at the opening ceremony by Dr. Bassem Yamout, president of MENACTRIMS; Dr. Raad Shaker, president of the World Federation of Neurology; Dr. Xavier Montalban, president of ECTRIMS; Dr. Suhayl Dhib-Jalbut, president of ACTRIMS; and Dr. Saeed Bohlega, president-elect of the Pan Arab Union of Neurological Societies.

The meeting hosted plenary sessions, scientific debates, clinical courses and symposia, focusing on biomarkers, epidemiology, immunopathogenesis, differential diagnosis, genetic and environmental factors, neuroimaging, OCT, pregnancy and Neuromyelitis Optica. More than 30 international and regional speakers shared their scientific and clinical experience with the audience, and 57 posters were presented during the meeting covering both local and international research.

MENACTRIMS is the youngest sister of a large family of international MS societies, which includes our elder sister ECTRIMS of nearly 30 years, ACTRIMS, LACTRIMS, PACTRIMS and RUCTRIMS. One of our main objectives is to cooperate with all international MS organizations to promote research and improve medical care in the field of MS.

Yamout is professor of Clinical Neurology, president, MENACTRIMS and director of the Multiple Sclerosis Center Clinical Research at the American University of Beirut Medical Center in Lebanon.

The Controversial Story of Aspirin

Figure 1. Felix Hoffmann

Edward Stone and aspirin

By JMS Pearce, MD, FRCP

For almost a century, aspirin, one of the most important drugs of the 20th century, was the mainstay of symptomatic analgesia, used universally in the treatment of headaches, arthritis, painful neurological and other maladies. Its introduction is usually credited to Felix Hoffmann’s (1868-1946) synthesis of salicylic acid in 1897. (See Figure 1.) But this is a controversial story. The use of salicylates dates back at least to c. 400 BC when Hippocrates (440-377 B.C.) prescribed the bark and leaves of salix, the willow tree (rich in salicin) to reduce pain and fever. It also was mentioned by Dioscorides (c. 100 A.D.) and later by Pliny the Elder and Galen.

In 1826, Henri Leroux isolated “salicin” from willow bark. However, it had fallen into disuse for centuries until the Reverend Edward Stone rediscovered its efficacy.

The Reverend Edward Stone (The Reverend was formally known as Edward, but was referred to as Edmund by his close friends and family.) was born in Lacey Green, Princes Risborough, Buckinghamshire, on Nov. 5, 1702¹. He went to Wadham College, Oxford, in 1720. In June 1728, he was ordained to take up the curacy of Charlton-on-Otmoor, Oxfordshire, where he remained until 1730 when he was elected a Fellow of Wadham. In 1745, he moved to Chipping Norton, Oxfordshire, as chaplain at Bruern Abbey.

Dried Willow Bark

Figure 2. Proc Royal Soc 1763, Edmund Stone: Willow bark

On April 25, 1763, Stone wrote to George Parker, second earl of Macclesfield, and president of the Royal Society in a letter read before the Royal Society on June 2, 1763, describing the use of dried willow bark as a remedy for fevers and agues². (See Figure 2.)

He explained that he had suffered from “aguistic intermitting disorders,” which may have been malaria. In 1757, he had “accidentally” tasted willow bark and noted its extreme bitterness and its resemblance to Peruvian bark (cinchona tree, source of quinine). Arguing from the doctrine of signatures —”that many natural maladies carry their cures along with them, or that their remedies lie not far from their causes,” Stone concluded that the willow tree that “delights in a moist or wet soil” might provide an antidote for agues that chiefly abound in that environment.

He experimented by gathering willow bark from pollarded willows, dried it for more than three months in a bag on the outside of a baker’s oven, pounded and sifted it. He dosed himself, using tiny amounts, but finding that the powder had a salutary effect, increased the dose to two scruples (One scruple equals 1/24 ounce, about 1.25 gm) every four hours. To his delight, “the ague was soon removed.”

Stone gave powdered willow bark over several years to about 50 people complaining of agues or fevers; it was successful in many of them. But, when fevers failed to respond to willow bark, he added quinine, which he found more effective. It’s unclear, however, if any of these patients had malaria. Thus, had Stone accidentally discovered a source of salicylate, the precursor of aspirin.

In January 1764, a fire at Bruern Abbey ended Stone’s chaplaincy there. He died intestate in Chipping Norton on Nov. 26, 1768, and was buried at Horsenden on Dec. 2, 1768.

After Stone’s report to The Royal Society², willow bark was advised in some herbals, and pharmacists tried to extract salicylic acid from willow bark and meadowsweet (Filipendula ulmaria). Side effects of salicylate were troublesome but were reduced when, in 1853, acetylsalicylic acid or aspirin was made by Hoffman from acetyl chloride and sodium salicylate.

It is usually stated that Hoffmann (See Figure 1.) developed aspirin to help his rheumatic father; but it was not until 1897 that under instruction from Arthur Eichengrün (1867-1949) he synthesized acetylsalicylic acid, which was named aspirin, for the Bayer company. (See figure 3.) Hoffmann’s close associate, Heinrich Dreser (1860-1924), dismissed the market potential of aspirin on the ground that it had an “enfeebling” action on the heart. (“The product has no value.³“) He was preoccupied at the time with the potential of Bayer’s new drug — heroin⁴.

Figure 3. Arthur Eichengrün

Arthur Eichengrün, whose job it was to discover new products at Bayer, refused to accept Dreser’s rejection of acetylsalicylic acid and pressed for its development^5,4. This was later produced commercially by Hoffman and Dreser in 1899, marketed by Bayer as “aspirin,⁶” whose name derived from Spiraea, then the Latin name for meadowsweet.

However, in 1949, Eichengrün claimed⁷ that he had instructed Hoffmann to synthesize acetylsalicylic acid, and Hoffmann had done so without understanding the purpose of the work. In 1944, while incarcerated in Theresienstadt concentration camp, Eichengrün had typed a letter (in the Bayer archives⁸) claiming his objective had been to obtain a salicylate without the adverse effects (gastric irritation, tinnitus) of sodium salicylate. Eichengrün tried aspirin himself, with no ill effects. Its real clinical potential was shown when with Dr. Felix Goldmann, he recruited physicians to secretly test it, they found it was successful in several painful conditions⁹. Eichengrün did not boast of his prime role in the discovery. Hoffmann lived until 1946, notably without publishing his own account of the discovery of aspirin; he mentioned repeatedly that Dreser had set the drug aside.

Hoffmann’s role was important but was restricted to the synthesis of aspirin: prompted by Eichengrün, who “deserved credit for the invention of aspirin.⁵”

References:

1. Mann R. ‘Stone, Edward (1702-1768)’, rev. Ralph Mann, Oxford Dictionary of National Biography, Oxford University Press, 2004; online edition, Jan 2008 [http://www.oxforddnb.com/view/article/38014, accessed 27 Sept 2014]

2. Stone E. ‘An account of the success of the bark of the willow in the cure of agues’, Philosophical Transactions Royal Society, 53 (1763), 195-200

3. Dreser H. Pharmakologisches über aspirin (Acetylsalicylsäure). Pflugers Arch 1899; 76: 306-318.

4. Askwith R. How aspirin turned hero. Sunday Times [London]. 1998 Sep 13.

5. Sneader, W. The discovery of aspirin: a reappraisal. BMJ 2000;321: 1591-4.

6. Fairley PA., The conquest of pain (1978) Aspirin Foundation, The amazing story of aspirin (1981) Foster, Alum. Oxon

7. Eichengrün A. 50 Jahre Aspirin. Pharmazie 1949; 4: 582-584.

8. Bayer-Archiv. 271/2.1 Personal data on Eichengrün. Dr A. Eichengrün, Aspirin, KZ Theresienstadt. 1944:2. Cited by Sneader,5.

9. Pearce JMS. The disputed origins of aspirin. In: Fragments of Neurological History. London, Imperial College Press. 2003.

Pearce is Emeritus Consultant Neurologist at the Department of Neurology, Hull Royal Infirmary, UK.

Dr. Peter J Koehler is the editor of this history column. He is neurologist at Atrium Medical Center, Heerlen, The Netherlands. Visit his website at www.neurohistory.nl.

Editor’s Update and Selected Articles From JNS

John D. England, MD

By John D. England, MD

The Journal of the Neurological Sciences (JNS) is a broad-based journal that publishes articles from a wide spectrum of disciplines, ranging from basic neuroscience to clinical cases. JNS strives to publish papers with novel, unique and original observations.

Along these lines, members of our Editorial Board are encouraged to identify and foster the submission of manuscripts that demonstrate the highest quality research. We also strive to satisfy the desires and needs of our readership, and I have received many requests to increase the number of review articles that cover topics in clinical neurology as well as basic neuroscience.

JNS has always welcomed well written and relevant review articles, and I wish to re-emphasize this point to prospective authors. Dr. Daniel Truong, who is the associate editor for Reviews and Commentary, has updated the suggested format for review articles submitted to JNS.

Whatever the topic, the review should be richly referenced and include summary text boxes, tables and diagrams or figures. The idea is to make the reviews easily readable and educational. Authors who might be interested in writing and submitting review articles to JNS can find specific requirements and suggestions within the JNS website.

In our ongoing attempt to enhance accessibility of JNS articles to members of the World Federation of Neurology (WFN), we have selected two more “free-access” articles, which are profiled in this issue of World Neurology.

In this issue, we feature two paired articles regarding the ALS-Plus syndrome.

Many clinical and pathological studies indicate that ALS is a more heterogeneous disease than previously recognized. In fact, even patients who appear to exhibit a clinically pure motor system disease often have neuropathological evidence of multisystem disease. In the largest series of cases to date, Leo McCluskey, et al, assessed the frequency of the “ALS-Plus” syndrome in a consecutively ascertained series of 550 patients with ALS. Their criteria for ALS-Plus was a clinical diagnosis of ALS combined with deficits of ocular motility, cerebellar signs, extrapyramidal features or autonomic dysfunction. Cognitive impairment was also assessed, but determined separately. Selected patients had genetic testing and high-resolution MRI of brain. Seventy-five (13.6%) patients had ALS-Plus syndrome. Fourteen additional patients had evidence of cognitive deficit (ALS-FTD). Cognitive impairment, bulbar-onset and pathogenic genetic mutations were more common in the patients with ALS-Plus syndrome compared to patients without ALS-Plus syndrome. The patients with ALS-Plus syndrome also had a shorter survival.
McCluskey L, Vandriel S, Elman L, Van Deerlin VM, Powers J, Boller A, et al. ALS-Plus syndrome: Non-pyramidal features in a large ALS cohort. J Neurol Sci 2014;345:118-124.
In an accompanying editorial, Benjamin Brooks provides an historical perspective and comments upon the importance of the article for the field of ALS research. He determines that McCluskey and colleagues have performed a “masterful clinical study of a modern series of ALS-Plus from a single center.” He suggests that this study provides a clinical framework for accurate classification of ALS-Plus syndrome. Studies such as this one indicate that “atypical” ALS is not as atypical as we believed and should stimulate more thought and research within the field.
Brooks BR. ALS-Plus – Where does it begin, where does it end? J Neurol Sci 2014;345:1-2.

England is editor-in-chief of the Journal of the Neurological Sciences.