The WFN welcomes Prof. Marianne de Visser to the position of co-opted trustee.

De Visser is an adult neurologist at the Amsterdam University Medical Center in Amsterdam, Netherlands, and emeritus professor of neuromuscular diseases at the University of Amsterdam.

She was trained as a neurologist at the University Hospital of Amsterdam. In 1988 and 1989, she was a visiting scientist at Andrew Engel’s lab at Mayo Clinic in Rochester, Minnesota, where she performed ultrastructural studies on skeletal muscle in dermatomyositis.

Her research interests are neuromuscular disorders and, in particular, myositis, ALS, post-polio syndrome, and hereditary neuropathies. Because of her work in ALS, she became interested in palliative care. Previously she was the president of the Netherlands Society of Neurology, and she served with distinction as a WFN elected trustee under Presidents Jun Kimura and Johan Aarli. Recently she stepped down as the secretary-general of the European Academy of Neurology.

De Visser will bring her extensive experience and her value of teamwork to the benefit of the WFN.

By Wolfgang Grisold

An international conference, focusing on “multidisciplinary strategies to prevent and combat brain diseases,” took place in Moscow on November 27-28, 2019, and followed the concept of integration and multidisciplinarity. The organization was smoothly run by Prof. Alla Guekht and her team and linked neurology to neurosurgery, internal medicine, and psychiatry. The meeting was held in the Buyanov’s city hospital, and needless to say was equipped with all facilities, including press briefings before the meeting.

The opening ceremony gave greetings from the Russian health care minister, Veronica Skvortsova, the Moscow head of the health care department, Alexey Khripun, the president of the All-Russian Society of Neurologists, Y.I. Gusev, and from the leading international neurological organizations — WFN, EAN, and ELAE. A short presentation about the WFN activities in regard to education, global networks, and cooperation with the WHO was made.

Dr. J. Breda, as the chair of the European regional NCD bureau of WHO, gave an initial presentation on the work of the WHO, primary care, and also aspects of environment and nutrition, which are eminently important for many non-communicable diseases (NCDs). This talk and statements are important for the mutual understanding of the specialization of neurology and the activities of the WFN. This was followed by a talk focusing on the historic role of Russian neurology. The impressive figure of the beginning of the 20th century, Bekhterev, was discussed, including his longing for innovation and his successful achievements in neurology, psychiatry, and health care organization and education.

During the first day of the conference, several other topics, such as stroke, rehabilitation, the autonomic nervous system, and neurooncology, were presented. Although these topics have defined contents being discussed at many occasions, the keynote speakers were able to pick out exciting developments and add valuable information.

The second day entered the often-neglected chapter of neuropsychiatry, which reemerges in international fields and undergoes a metamorphosis from conversion into functional disorders. This lecture by Prof. W. Curt LaFrance Jr. (U.S.) made two important points: functional disorders exist and may be more frequent than we admit, and several concepts of explanation and treatment were available. Another message was that a society for functional disorders has been recently established.

A complex of lectures discussed epilepsy and seizures. Epidemiology and the complex meaning of incidence and prevalence were beautifully and carefully explained by Prof. W. Allen Hauser (U.S.), who shared his insights into this important basis of his work and considerations. Several other lectures addressed epilepsy and seizures, and were supported by excellent videos of patients, EEG recordings, and imaging.

The end of the second day was devoted to carefully prepared case presentations, which focused on several topics, such as complicated cerebrovascular disease, genetic diseases, complex seizures, neuroinfections, and rare neuropathies. In several cases, speakers from other disciplines were invited to make valuable comments and give diagnostic clues. The spirit of these case presentations was enthusiastic and also made it clear that neurology is deeply rooted in multidisciplinary and multiprofessional work. From the engagement of speakers and the audience, these short case presentations seemed to become a well-accepted format.

On the third day, there was a meeting in the Moscow Research and Clinical Center for Neuropsychiatry within the international advisory board of the center. The members of international and Russian faculty discussed ongoing collaborative projects on comorbidity of epilepsy and mental disorders, self-harm behavior, the role of neuroinflammation in stress, and some others. Junior researchers of the center presented their papers and interesting cases.

Research labs and clinical facilities of the center were presented. The members of the board appreciated the high level of the technologies in the labs and the clinical wards of the center.

The size and the spirit of the meeting also allowed many personal and professional interactions, and faculty members interacted with local neurologists, allowing the platform for advice and cooperation to continue.

Having attended these meetings for brain diseases for several years, the interaction of attendees with the faculty is increasing, the magnitude of interaction and discussion during the meeting is developing, and the impression is that young neurologists and psychiatrists are increasingly fluent in English, which helps increase cooperation and communication. These types of integrative meetings, with a strong educational accent, are valuable not only from the point of content, but also from communication.

Wolfgang Grisold is Secretary General of the WFN.

 

 

BY CHANDRASHEKHAR MESHRAM

Neuroinfections form a large group of disorders commonly seen by neurologists as well as other physicians. Old, new, and emerging infections, their patterns of presentations, and imaging features as well as therapies pose challenges in practice. There are not many meetings that address these issues. Therefore, the Tropical and Geographical Neurology Specialty Group of World Federation of Neurology (WFN) in collaboration with the Forum for Indian Neurology Education (FINE) and under the aegis of the World Federation of Neurology has organized a neuroinfection webinar series. This program is dedicated to Prof. Jagjit Singh Chopra.

The webinar-based meeting began on July 18, 2020, and will run every Saturday 7-9 p.m. Indian Standard Time (IST)/1:30-3:30 p.m. Coordinated Universal Time (UTC). There will be a weekly lecture by a renowned neuroinfection expert, covering many aspects followed by presentation and discussion of three cases.

Registration is free, and the link for registration can be found here: http://neurologycourses.com/user/registration.

The program can be accessed at https://us02web.zoom.us/j/801815712 using the password “ilovefine” with no punctuation.

The event was formally inaugurated on July 18 by Prof. Raad Shakir, former president of the WFN and chair of the specialty groups. Prof. Hector Garcia, from Peru, delivered the first talk in the series on neurocysticercosis. Participants had the opportunity to interact with the speaker through a question and answer session after the talk. This was followed by presentation and discussion on three interesting and challenging cases.

Subsequent talks will be on Saturday, July 25, by Prof. Erich Schmutzhard (Austria) on cerebral malaria, on Aug. 1 by Prof. Marco Tulio Medina (Honduras) on Zika and other arbovirus infections, on Aug. 8 by Prof. Riadh Gouider (Tunisia) on neurobrucelloisis, on Aug. 15 by Prof. Serefnur Ozturk (Turkey) on encephalitis, on Aug. 22 by Prof. Jeremy Day (Vietnam) on cryptococcosis, on Aug. 29 by Prof. Avindra Nath (USA) on the approach to neuroinfections, and on Sept. 4  by Prof. Joseph Berger (USA) on fungal infections of the CNS.

Interesting and challenging cases of dengue, chikungunya, rabies, ebola virus, nipah encephalitis, neuroschistosomiasis, neurognathostomiasis, trypanosomiasis, onchocerciasis, neuroangiostrongylosis, amoebic encephalitis, sarcocystosis, CNS TB, HIV, and other diseases will be presented and discussed during the series.

We welcome delegates from different countries to participate and present the cases. Those interested in presenting cases should write to the moderators of the program. Chandrashekhar Meshram, president of the Tropical and Geographical Neurology Specialty Group, is the program director. Gagandeep Singh and Rahul Kulkarni are moderators, while Sudhir Kothari and Roop Gursahani are advisors.

By Avindra Nath and B. Jeanne Billioux

It is becoming increasingly apparent that many patients who recovered from the acute phase of the SARS-CoV-2 infection have persistent symptoms. This includes clouding of mentation, sleep disturbances, exercise intolerance, and autonomic symptoms. (See Tables 1 and 2 below) Some also complain of temperature dysregulation and lymphadenopathy. Although there are no peer-reviewed papers at the moment on these patients, many news articles have been written about this phenomenon^1-4 and apparently there are Facebook pages where there are several thousand patients with these symptoms. They describe themselves as the “Long-Haul-COVID” or “Long-Tail COVID.” Many of these patients are health care workers who had massive exposure to the virus early in the pandemic and describe having symptoms for 100+ days. Since many of the symptoms are neurological in nature, these patients are seeking us out for help. It is important that we characterize these patients and try to document the objective findings and then determine how best to study their pathophysiology to develop proper guidelines for treatment.

Most of these patients were in excellent health prior to getting infected with SARS-CoV-2. They all had myriad symptoms during the acute phase; however, as the fever and respiratory symptoms improved, they are left with persistent systemic symptoms, some of which are gradually improving, but not all are following that course. While some were admitted to the hospital due to pulmonary symptoms, the majority were isolated at home. Many of these symptoms overlap with those of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The cause of ME/CFS remains unknown despite decades of research of the syndrome. Many of these patients similarly report a viral infection as a trigger, but since they come to our attention months and years after symptom onset, it is impossible to know what may have triggered the symptoms.

Long-Haul COVID thus represents an excellent opportunity to study the pathophysiology of ME/CFS that may have broader implications. It is unclear at present if these patients may have endocrine abnormalities, but certainly with SARS-CoV-1, hypothalamic/pituitary dysfunction and adrenal insufficiency has been reported⁵. It would, of course, be equally important to determine if there might be any premorbid conditions or medications that might contribute to these symptoms.

Even at this early stage, it might be important to determine what the potential pathophysiological mechanisms might be. So far there is no convincing evidence for widespread infection of the brain with the virus. The virus has been detected in CSF and the brain in very rare cases; however, there is evidence for widespread glial cell activation that may be related to metabolic dysfunction or to the massive immune activation in the periphery. Other possibilities are specific immune responses targeted against specific regions of the brain and autonomic nervous system. Depending on the predominant underlying pathophysiological mechanism at play, targeted treatment might be possible.

Unfortunately, it looks like the pandemic has gotten out of control. It is spreading rapidly across the globe, and even if we have an effective vaccine, we might never have enough dosages to vaccinate the eight billion inhabitants on this planet. And we also have a subset of the population that is opposed to any kind of vaccination. So COVID-19 is here for the long haul, and neurologists are going to play a critical role in the management of these “Long-Haulers.” Several efforts are underway to prospectively follow these patients with persistent symptoms, including studies at the intramural program at the United States National Institutes of Health in Bethesda, Maryland. Hopefully we can get to the bottom of these manifestations soon and find solace for these patients in a timely manner. •

Avindra Nath, MD, is chief of the Section of Infections of the Nervous System and Clinical Director, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health in Bethesda, Maryland.

Jeanne Billioux, MD, is staff clinician and head of the program in International Neuroinfectious Diseases within NINDS. Her research focus is on emerging infectious diseases and conducting research on the neurological consequences of infections in an International setting.

References:

1. https://www.wsj.com/articles/three-months-in-these-patients-are-still-ravaged-by-covids-fallout-11593612004
2. https://www.washingtonpost.com/health/could-covid-19-cause-long-term-chronic-fatigue-and-illness-in-some-patients/2020/05/29/bcd5edb2-a02c-11ea-b5c9-570a91917d8d_story.html
3. https://www.bloomberg.com/news/videos/2020-06-10/the-lingering-symptoms-of-covid-19-video
4. https://www.washingtonpost.com/health/2020/06/11/coronavirus-chronic/?arc404=true
5. Leow MK-S, Kwek DS-K, Ng AW-K, Ong K-C, Kaw GJ-L, Lee LS-U. Hypocortisolism in survivors of severe acute respiratory syndrome (SARS). Clin Endocrinol. 2005;63(2):197-202.

by Peter J. Koehler

The relation between civilization and disease has been known for centuries. Researchers found evidence that in the pre-history period, small hunter-gatherer populations tended to be less troubled by disease. With growing population density following the settlement of farmers around 12,000 years ago (in the Neolithic period), and later the start of commercial traveling and increasing mobility, pathogens could spread easier. Yersinia pestis (bubonic plague in the Late Middle Ages), Treponema pallidum (syphilis, starting around 1500), and Variola (smallpox, in particular during the 17^th and 18^th century) are well-known examples. Sometimes whole nations were associated with a disease, the best example being the “Spanish disease” and “morbus Gallicus,” referring to syphilis. In the Renaissance period, there was already some knowledge about the spread, and quarantine protocols were promoted in some places upon the arrival of ships (40 days, hence the word quarantine, from the French “quarant”). In periods of plague, markets and city gates were closed.

Not Only Contagious Diseases

Another type of disease of civilization was recognized in the 18^th century and associated with the “secularized revamping of the Christian legend of the Fall, wherein Original Sin and the expulsion from Paradise had inaugurated the regime of hard labor, disease, suffering, and death in the temporal world.”1 Several physicians in this period, including the Scottish physician George Cheyne (1672-1743; Figure 1; not to be confused with John Cheyne [1777-1837]), who practiced in London and Bath, and the Swiss physician Samuel August Tissot (1728-1797; Figure 2), and also philosopher Jean-Jacques Rousseau (1712-1778) pointed to the relatively healthy hunter-gatherer and peasant people of the early days, who were engaged in physical labor, exercise in the open air, and taking healthy foods. Town life in the 18^th century with its commerce, wealth, indoor work, and bad habits, including taking too much food and alcohol and too little exercise, could easily lead to health problems, which often resulted in the use of opiates, tobacco, more alcohol, and remedies.¹ According to Tissot, “gens des lettres” were particularly prone, and he even dedicated a book to the subject in 1768, De la santé des gens des lettres [On the health of men of learning], which was published in several editions at least up to 1826 and considered an important publication in the history of occupational disease. In his preface, the author indeed referred to the pioneer Bernardino Ramazzini (1633-1714, author of De Morbis Artificum Diatriba / Diseases of Workers).

Tissot’s Santé des gens des lettres

In his De la santé des gens des lettres (Figure 3), Tissot referred to numerous cases from medical literature described by well-known physicians. The association was already known ages ago, as for instance Galen of Pergamon (129-c210) described the history of the peripatetic philosopher Premigenes, who lived a life of reading and writing, thereby not perspiring well, for which he had to take a bath every day, to avoid accumulation of the sharps humours.² More recent physicians included Jean Fernel (1497-1558), Johann Jakob Wepfer (1620-1695), and Giovanni B. Morgagni (1682-1771), who associated mental efforts and exhaustion, which led to severe or even mortal disease. Wepfer, for instance, mentioned the case of a young man (22 years old), who studied day and night, became delirious, hurt several people, and killed his guard.² Tissot also referred to Gerard van Swieten (1700-1772) and his Commentaria in Hermanni Boerhaave aphorismos de cognoscendis et curandis morbis (5 vols. 1742-72), in which he wrote about “Les Gens de Lettres qui mènent une vie sédentaire, & qui pâlissent sur leurs livres, sont souvent exposés à une apoplexie.” [“Men of learning, who live a sedentary life, and turn pale above their books, are often exposed to apoplexia.”)² Hypochondria was also a well-known ailment, Tissot believed. “Parmi les maux que la vie sédentaire de Hommes des Lettres produit presqu’inévitablement en dérangeant la circulation dans les viscères du bas-ventre & y produisant un principe d’obstructions, on doit comptant l’hypocondrie.” (“Among the ailments that are almost inevitably caused by the sedentary life of men of learning by deranging the circulation of the bowels of the abdomen and there producing a source of obstructions, one has to reckon hypochondria.”)² Tissot not only wrote on men, but also mentioned women, for instance a 50-year-old woman, who had read books at night in her youth and then started suffering from insomnia and fluxions. With respect to the causes, he mentioned the air around these persons that was rarely freshened, in contrast to the pure and fresh air from the fields, continuation of the work during a part of the night, and lack of exercise leading to “cardialgia,” which had already been noted by Aretaeus of Cappadocia (first century CE) and Aetius of Amida (mid-fifth and mid-sixth century).²

Rousseau

At the time, a well-known critic of civilization was Rousseau. An interesting section of Tissot’s book deals with the preface of Rousseau’s play Narcisse ou l’amant de lui-même (“Narcissus or the lover of himself;” 1753). Reading the original text, Rousseau indeed wrote about his concerns with respect to “Le goût des lettres, de la philosophie & des beaus arts amollit les corps & les ames.” (“The fondness of letters, philosophy, and fine arts, weaken the body and soul.) He continued, noting that “Le travail du cabinet rend les hommes délicats, affoiblit leur tempéramment, & l’ame garde difficilement sa vigueur quand le corps a perdu la sienne. L’étude use la machine, épuise les esprits, détruit la force, énerve le courage, et cela seul montre assez qu’elle n’est pas faite pour nous : c’est ainsi qu’on devient lâche et pusillanime, incapable de résister également à la peine & aux passions.” (“Office work makes people delicate, weakens their temperament, and the soul can keep its strength more difficult, when the body has lost it. Study wears out the machine, exhausts the spirits, destroys the power, weakens courage, and just that sufficiently shows that it has not been made for us: This is how one becomes unresisting and faint-hearted, incapable to resist distress as well as passions.”)

Seated in the Nervous System

Several physicians, including the mentioned Cheyne and Tissot, believed that these modern diseases from abundance and sedentary life had their seat in the nervous system, writing about a nervous tone. These physicians did not always apply contemporary humoral pathophysiological theories that still reigned, at the time (although Cheyne was still writing in terms of “interruption or interception of the vibrations of the nerves by the viscidity of juices”). The excessive food and alcohol, in combination with a lack of exercise, would result in obstruction of nervous fibers that led to all kinds of complaints that were not observed in people who led a healthier life in the countryside. The term “nervousness” became fashionable for physicians as well as patients. Physicians came to believe that many of the current diseases had a nervous origin. Remarkably, nervous disorders had a positive connotation as it was believed to be observed in particular in intelligent and rich people, the beau monde. Interestingly, gout, at the time, was another disease that had the same connotation and was associated with wealth, food, and alcohol.

In this way a psychosomatic paradigm seemed to play an important role in the age of Enlightenment. Not only organic causes, but also ideas, imagination, and emotions were taken into consideration. Much more could be said about the further development of this concept during the 19th century — degeneration ideas, social Darwinism, nervous exhaustion, and neurasthenia with the work of George Beard (1839-1883) and Silas Weir Mitchell (1829-1914) — and 20^th century — eugenics starting with Francis Galton (1822-1911) and ending in the Nazi cruelties — but let us keep to the 18^th century here.

Cheyne’s English Malady

Not only the mentioned part of society was susceptible for these diseases, but even whole nations were associated with it. Cheyne’s book was named The English Malady (Cheyne, 1733; Figure 4). In the preface he noted that “all our Neighbors on the Continent, by whom nervous Distempers, Spleen, Vapors, and Lowness of Spirits, are in Derision called [it] the English Malady. And I wish there were not so good Grounds for this Reflection.” He continued to mention the reasons for this, including “the Moisture of our Air, the Variableness of our Weather … the Rankness and Fertility of our Soil, the Richness and Heaviness of our Food, the Wealth and Abundance of the Inhabitants (from their universal Trade), the Inactivity and sedentary Occupations … and the Humor of living in great, populous and consequently unhealthy Towns.”⁴ Furthermore, it is of interest to write out the whole title of the book, as it occurs on the title page, The English Malady: or, a Treatise of Nervous Diseases of all Kinds, as Spleen, Vapours, Lowness of Spirits, Hypochondriacal, and Hysterical Distempers, as well as the titles of the three divisions of the book, notably Part I. Of the Nature and Cause of Nervous Distempers; Part II. Of the Cure of Nervous Distempers; Part III. Variety of Cases that illustrate and confirm the Method of Cure; to which Cheyne added “With the Author’s own case at large.”

In chapter six, “of the Frequency of Nervous Disorders, in later Years, beyond what they have been observed in former Times,” we find information on the three main causes, including 1) luxury; 2) an inactive, sedentary, or studious life; and 3) living in great and populous cities. Most, if not all, of the cases described came from the higher classes, indeed finishing with an extensive description of his own condition, with intermittent fever and “vertiginous Paroxysm, so extremely frightful and terrible, as to approach near to a Fit of an Apoplexy … I found after this, some small Returns of my Vertigo (in Bed especially) on lying on a particular Side…” (This episode seems to have been benign paroxysmal positional vertigo.) Later he suffered from headache, depression, and anxiety, as he “went about like a Malefactor condemned, or one who expected every Moment to be crushed by a ponderous Instrument of Death”. ⁴

In general, the nervous distempers were usually treated by medicaments, diet, and exercise. The author himself resorted to omitting suppers, eating less animal food at dinners, “and drinking very little fermented Liquor,” which resulted in losing several of his friends. He retired to the countryside “into the fine Air,” took medicaments, had setons made in the neck, and took gentle purges. He suffered from melancholy, lost weight, and called it a “Nervous and Scorbutical Disorder.”4 In his Essay on Regimen (1740), which is often quoted by vegetarians, as he advised vegetables rather than animal food, he even provided a number of aphorisms “to instruct and ease the Memory of the Valetudinarian.” Among the regimens, he emphasized horseback riding in aphorism no. 25: “Rideing is the best of all Exercises to get Health, and to promote the Digestions, especially in nervous Distempers”.5 He believed “Hypochondres are thereby most shaken and exercised.”4 In a letter to writer and printer Samuel Richardson (1689-1761), Cheyne advised “riding on the new Chamber Horse so well known in London. It is certainly an excellent Contrivance for the Sedentary, Studious, and Thinking Part of Mankind except the fresh Air.” He was using the device himself an hour every day and “do more when the Weather will not permit me to walk in the Garden or ride my Coach.”

Nosological Systems and Neurosis

The importance of the nervous system as the origin of diseases was also recognized by Robert Whytt (1714-1766), professor of the theory of medicine at the University of Edinburgh, although he had a different approach. He noticed that nervous diseases may mimic somatic conditions and can be strongly influenced by emotions, sometimes being triggered by intense imagination. His successor Wiliam Cullen (1710-1790), who drew up an important nosological system, believed that the category of nervous diseases — he coined the term neurosis — was the most important among four categories (although historian of science Dyde pointed to the differences of view with this respect between Whytt and Cullen). In this age of nosology, in which diseases were classified in a similar way as Carl Linnaeus (1707-1778) did with the plant world (he also made a nosological system of diseases), Cullen classified diseases into 1) pyrexiae (fevers); 2) neuroses ; 3) cachexiae; and 4) locales (Figure 5). His classification influenced the French physician Philip Pinel (1745 – 1826), who recognized neuroses of the senses, cerebral function, locomotion and voice, nutrition, and sexual function. It may be regarded a mixture of diagnoses from modern neurology and psychiatry, although other diseases were still classified within this category. The class of neurosis mainly included diseases that Pinel considered “functional,” and this contained more diseases than we would call psychiatric nowadays (and the term cannot be equated with its later use by Freud). This functional orientation of neurosis remained during almost the whole 19th century, though the category of neuroses became smaller in the course of the century as more diseases were found to have a neuropathological substrate. In the 1880s, for example, William Gowers (1845-1915) mentioned the following functional disorders: chorea, paralysis agitans, tremor, tetanus, tetany, occupation neurosis, etc.

Conclusion

In conclusion, the 18^th century disease of civilization, associated with abundance and sedentary life, and its treatment looks familiar to us today. The association these physicians made with the nervous system is of interest against the background of the psychosomatic perspective. The concept of nervous disorder or neurosis at the time, however, was much broader than today, a kind of repository, and cannot be compared with its use in the early 20th century (psychoneurosis).

 

 

by Louis R. Caplan, Oxford University Press 2020

by Vladimir Hachinski

Who was the greatest contributor to the field of stroke in the 20th century?” If you answer the question, you risk displeasing somebody somewhere with a different opinion. On being asked that question after a lecture in Moscow, I answered: “The greatest contributor to the understanding of the common causes of stroke is C. Miller Fisher.” Few would disagree. He established the relationship of carotid disease to ischemic stroke, characterized the clinical and pathological feature of lacunar syndromes, and proved that atrial fibrillation can cause stroke in the absence of cardiac valvular disease.

Lou Caplan is one of Miller Fisher’s most distinguished pupils and colleagues. He describes these and others of Miller Fisher’s contributions in historical context.

Carotid Disease

Hans Chiari in 1905 described the relationship of carotid stenosis to stroke. If the implications were ever appreciated, they were soon forgotten. Transient ischemic attacks (TIAs) were recognized, but most physicians accepted the explanation offered by the great Canadian/American/British physician William Osler, who attributed them to “vasospasm.” The explanation of vasospasm as a cause of TIAs proved plausible, convenient, and wrong. Miller Fisher observed the transient platelets and other materials through the retinal arteries during a TIA and concluded that embolism from the extracranial arteries was the common cause of TIAs. It was MiIler Fisher who established that carotid disease could lead to stroke and laid the scientific bases for carotid endarterectomy.

Lacunar Syndromes

Miller Fisher described five classical lacunar syndromes based on extensive clinical observations and meticulous brain dissections. As atherosclerotic large vessel disease decreases with better treatment, small vessel disease gains greater prominence.

Atrial Fibrillation

When Miller Fisher began his career, atrial fibrillation as part of rheumatic heart disease was recognized as being associated with stroke, but not as a cause by itself. In 1977 he published a study that left no doubt that atrial fibrillation by itself could cause stroke though cardiac embolism. Even before his definitive study, he had been advocating prophylactic anticoagulation in atrial fibrillation, still the mainstay of prevention.

Caplan’s own clear writing is enhanced by quotes from Miller Fisher’s detailed memoirs spanning a long life. The main headings make for easy reading and scanning.

Caplan’s direct knowledge of the field, of the main players and his own contributions allow him to state: “This book is also in many ways a biography of a disease (stroke) as it evolved during the 20^th century.” This is not to deny the contribution of others, as Caplan has documented himself in his co-edited book on stroke syndromes, nor the fact that advances in the field increasingly are made by contributions from all around the world.

Caplan manages to convey a sense of the times and how a field dominated by therapeutic nihilism became one of a growing array of treatments and interventions. Caplan’s scene-setting illustrated by Miller Fisher’s own words also convey a sense of the man: Miller Fisher as a doctor, naval officer, survivor of a torpedoed ship, prisoner, prison physician, neurologist, neuropathologist, teacher, mentor, and thought leader. He, along with his many pupils and the pupils of pupils, has played a major role in transforming the field. These include Robert Ackerman, Lou Caplan, Steven Cramer, Stephen Davis, Geoffrey Donnan, Phillip Kissler, Walter Koroshetz, JP Mohr, Alan Ropper, Martin Samuels, and Philip Wolf, among many others.

Seldom has a medical story been told so well, so credibly, and so accurately by someone who has been a partner and participant in the advances that he describes. It is a delight to read by anyone with a health sciences background, and a must for those in the field of stroke. George Santayana wrote, “Those who cannot remember the past are condemned to repeat it.” We do want all those involved in stroke to remember the past, so that we can have many repeats of Miller Fisher’s inspiring example in the multiplying subfields of stroke.

Vladimir Hachinski, MD DSc is Distinguished University Professor, University of Western Ontario London, Canada, and a past president of the WFN.