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Home , Neurology, Neuropathology, Percival Bailey

Chapter  E. Tessa Hedley-Whyte, David N. Louis, Umberto De Girolami, and Matthew P. Frosch

europathology has a long tradition microscopical study of the tissue sections, to Nat the Massachusetts General Hospital gain some insights as to the presence of any (MGH). Among the various anatomical pathol- process, and as to its nature. Th e cells ogy at the MGH, it is the oldest, in and fi bers that are disclosed by the microscope terms of both dedicated faculty and are dead, immobile structures; and yet, they a subspecialty training program. In its extensive are actors in a drama that are suddenly held history it has demonstrated excellence in clini- still in the midst of their activity—in the midst cal care, education, and research, and many of of each pose or gesture—as in a photograph. its successes have been attributed to the extraor- It is the task of the tissue pathologist—and of dinarily close interactions between Neuropathol- the neuropathologist in this fi eld of his activ- ogy and its associated departments, initially Psy- ity—to infer, by means of his previous experi- chiatry and and later , ence with other cases or with evidence of older which continue to this day. or more recent stages of the disease process in Some of the character of MGH Neuropathol- the same case, what the scenes were that have ogy is captured in an earlier account of the his- gone on before, and what might have resulted tory of the Neuropathology Laboratory by E. P. had not the whole process terminated at that Richardson Jr., published in Th e News at MGH point. Viewed in this way, the scene may be in 1957 (1). Th e paragraph quoted below high- that of a furious battle with hordes of cellular lights both the complexity of the participants in various degrees of victory or and the excitement of discovering its pathologi- defeat; or it may be more like a gradual, insidi- cal processes, and thus serves as an appropriate ous decline and decay. Th us, in the mind’s eye, introduction to this chapter: the picture is no longer that of a dead stillness but, instead, of an active struggle between It may be wondered why it should be necessary the forces of health and those of disease—the to spend so much eff ort on the pathological meaning of which may be readily apparent, or examination of a single organ; yet it is quite may yet defy interpretation. Or, it may be—as apparent that the nervous system is itself made often is the case—that the fl orid manifesta- up of a large number of tissues, with intercon- tions observed during life are not refl ected in nections of inconceivable complexity, and that any visible disturbances in the structures under a large number of areas must be examined in scrutiny. Th is, too, must be discovered and order to reach some idea as to the whole. Th us, understood. It must be admitted that there are the neuropathologist attempts, by the detailed disease processes which do not result in any

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changes that can be observed with the ordinary in Europe with both pathologists and neurolo- microscopical techniques at our disposal. Our gists, including Carl von Rokitansky, Th eodor methods are still inadequate to reveal subtle Meynert, and John Hughlings Jackson, and went structural changes which must surely be present on to become one of the founders of the American in many instances, and this must be an incen- Neurological Association. While he was Chief of tive to improve our techniques. Even then, it Neurology at MGH, he converted a portion of may well be that some cases of what could be his home into a neuropathology laboratory. His called “disease” cannot be elucidated by any primary interests were in clinicopathological cor- method of demonstrating structures, no matter relations based on studies. how refi ned. Th is, too, we must know. Dr. Edward Wyllys Taylor trained in neuropa- thology in Berlin with in Th e history of neuropathology at MGH can 1891–1893. He returned to Boston as Assistant in be divided into four partially overlapping eras: at HMS in 1893. Infl uenced by Drs. 1. Before 1927, when a formal neuropathol- J. J. Putnam at the MGH and W. N. Bullard at ogy unit was established. During this period Boston City Hospital, Dr. William T. Council- surgical neuropathology was performed by man established a neuropathology laboratory the anatomical pathologists and research and for Taylor at HMS in 1902 (2). Dr. Taylor, while autopsy neuropathology by the pathologists an Instructor in Neuropathology at HMS and a and neurologists member of the Neurological Department of the MGH, published a classic paper on the patho- 2. From 1927 until 1951, when the Neuropathol- logical anatomy of poliomyelitis in 1902 (3). He ogy Clinical Service was managed largely by a argued that infl ammation of the ventral horns single individual, Dr. Charles S. Kubik, and caused motor death rather than direct neuropathology research was collaborative of the themselves, and he made with other individuals and departments, nota- it clear that this was a controversial issue; none- bly Dr. in theless, it was agreed that the disease was due to 3. From 1951 through the late 1980s, during an infectious agent. He wrote on a variety of neu- which Neuropathology was directed by Dr. ropathological topics, including “Four Defective Edward P. Richardson Jr. and dominated by ” (4). Dr. Taylor succeeded Dr. Putnam as the three “giants”: Drs. Raymond D. Adams, Chief of Neurology at MGH in 1906 and was C. Miller Fisher, and Richardson later appointed the fi rst James Jackson Putnam Professor of Neurology at HMS. 4. From the late 1980s to the present day, when In 1912 Harvard University established the joint the Neuropathology group grew in terms of Department of Psychiatry, Neurology, and Neu- number of faculty and research resources, and ropathology (5). By that time there was already a during which time the directorship was trans- Bullard Professor of Neuropathology, Dr. Elmer ferred from Richardson to Dr. E. Tessa Hed- Southard, the Bullard Foundation for Neuropa- ley-Whyte and then to Dr. Matthew P. Frosch. thology at HMS having been established in 1906. Dr. James Homer Wright (chapter 4), the The Early Days: Before  Chief of Pathology from 1896 to 1926, wrote a In 1872 Dr. James Jackson Putnam was the fi rst number of papers on neuropathology. His report neurologist appointed to the MGH staff , and in the minutes of the Boston Society of the he founded the Neurology Department at Har- Medical Sciences in 1897 describing an “unusual vard (HMS). He had studied degeneration of the , in which there

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was a well marked tract of ascending degenera- Pathology may have been one factor in the 1926 tion in one of the columns of Burdach,” second- decision (once he was Chief of Neurology) with ary to a metastatic breast cancer in the sacrum, Dr. Tracy Mallory to establish a neuropathology demonstrated that he had a good knowledge of laboratory that involved both the departments of (6). Dr. Wright followed this with Neurology and Pathology. a comprehensive monograph, with Dr. Coun- cilman of HMS and Dr. Frank Burr Mallory of Charles S. Kubik: The Early, Boston City Hospital, on 111 cases of epidemic Pre-MGH Years meningitides for the State Board of Health of Charles Soucek Kubik (fi gure 17.1) was born in Massachusetts in 1898 (7). Dr. Oscar Richardson Caldwell, Kansas, on February 4, 1891, and died (see chapter 3; no relation to E. P. Richardson Jr.), in Lincoln, Massachusetts, on June 5, 1982, at the who was Dr. Wright’s close associate for nearly 30 age of 91. He was one of six children and grew up years, also contributed to the neuropathological on the family farm, where the family raised wheat literature, detailing a case of Friedreich’s in and other crops and established peach, apple, and 1898 (8). cherry orchards. As a youngster, he became adept Dr. Wright left another indelible mark on neu- at many chores on the farm, hunted, fi shed, and ropathology, albeit indirectly. His seminal study attended a nearby small country schoolhouse. of adrenal neuroblastoma, with its description of He attended Caldwell High School, getting to the characteristic rosettes that now bear his name, infl uenced the terminology used to describe other tumors showing similar neuronal diff er- entiation, including primitive neuroectodermal tumors of the such as (9). Th e term Homer Wright rosette has long been in common usage in neuropathology practice, far more so than the equivalent Bailey’s pseudorosette, named after , who described it in . Th e laboratories of the Pathology Department also played a role in neu- ropathology. Analysis of the cerebrospinal fl uid (CSF) was increasingly performed, the empha- sis being on the detection of . In 1922 the neurologist Dr. James B. Ayer, who had been working in the Pathology Department on a variety of projects of neuropathological inter- est, expanded the study of CSF to include cer- tain routine examinations (total protein and col- loidal gold) and other special tests (gum mastic and quantitative sugar). In 1922, 1,375 total pro- tein, 908 colloidal gold, 374 gum mastic, and 228 quantitative sugar measurements on CSF were made. By 1924 the number of spinal fl uids Figure 17.1 Charles S. Kubik, Director of examined was 2,016. Dr. Ayer’s close work with Neuropathology 1927–1951, mid-1930s

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school on horseback and staying with another that time there were only about 10 established family during the week because of the long dis- laboratories dedicated to the study of neuropa- tance from the farm; he graduated in 1908. He thology and neurohistology in the world, notably went on to receive his undergraduate degree from at the National Hospital for Nervous in the University of Kansas in 1912 and his M.D. in London; the laboratory of Jean-Martin Char- 1916 from Rush Medical College in Chicago. cot and Charles Foix in Paris at the Salpêtrière Dr. Kubik was accepted as an intern at Cook (which had such students as , County Hospital in Chicago in 1916, but World , William James, and Alfred War I intervened. He volunteered in the U.S. Binet); distinguished centers in Breslau, Frank- Army and served as Captain, Medical Corps, in furt, Munich, and Berlin (12); and the laboratory the 131st Ambulance Company in the 33rd divi- of Santiago Ramón y Cajal in Madrid, in which sion in France, from 1917 to 1919. Following the the seminal neurohistological studies were made war, he returned to Kansas to practice general that eventually led to Cajal’s Nobel Prize. . In 1924 he decided to pursue train- From its inception, the MGH Neuropathol- ing in neurology and psychiatry and went to the ogy Laboratory had from the depart- National Hospital for Nervous Diseases (now the ments of Neurology, Neurosurgery, Pathology, National Hospital for Neurology and Neurosur- and Psychiatry in the laboratory participating in gery) at Queen Square in London, which was at the study of cases. Th e original Neuropathology the time the preeminent center in the English- Laboratory was situated on the second fl oor of speaking world to train in neurology. Founded in the Allen Street Building. Initially, Dr. Kubik had 1859, it was the fi rst hospital in Britain dedicated to borrow a microtome to cut tissue sections— to the study of neurologic illness. Th ere he also until the day he stumbled across one (1): “Even- studied neuropathology under the stewardship of tually, Dr. Kubik did obtain a microtome for the Dr. J. G. Greenfi eld, the author of what became newly created laboratory. It happened that one the standard textbook in the fi eld (10, 11). Indeed, day he chanced to notice, hidden away under Kubik was one of Greenfi eld’s fi rst fellows. Dr. the seats of the old Pathology Amphitheatre and Greenfi eld became a valued mentor, colleague, heavily coated with the untouched dust of many and friend, and when he visited Dr. Kubik at his years, an abandoned microtome, which further home in Massachusetts in 1956, Dr. Kubik gath- inspection showed him was still serviceable and ered his MGH Neuropathology and Neurology of a type particularly suited for cutting neuro- department colleagues to honor him. pathological tissue sections. Th is was resurrected After completion of his training in neurology from its dusty repository and it performed use- and psychiatry, Dr. Kubik returned to America in fully for years.” 1926 and joined the Boston Psychopathic Hospi- At fi rst, Dr. Kubik cut and stained all his own tal as a house offi cer in psychiatry. Th ere he met sections, which were reportedly “beautifully cut his wife-to-be, Emily Knapp, a chemist working and stained sections which remain as examples at the hospital. Soon thereafter, Dr. Kubik was and inspiration for those who have followed him invited by Drs. Ayer and Mallory to found a neu- in this work” (1). Soon, however, as the service ropathology laboratory at MGH. grew, Dr. Kubik recruited skilled technicians to help, initially Jean Engborg, who joined the From  to : The Kubik Era laboratory in 1930 and who stayed a part of it Th e special laboratory for Neuropathology in the through the late 1950s. Even after her retirement, Department of Pathology at MGH was estab- Engborg continued to travel from Maine to the lished in 1927 under Dr. Kubik’s leadership. At laboratory to perform silver impregnations on

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frozen sections. Th e early group of technicians included Klara Edwards, the Chief Technician in Neuropathology from the late 1940s until fi nally retiring in 1979, whom E. P. Richardson noted for her “ceaseless interest and conscientious work of the highest quality” (1). Olgerts Zvaigzne, who worked primarily in Dr. Adams’s Experimental Neuropathology Laboratory, was an expert in celloidin embedding and prepared whole brain sections for the clinical laboratory. Kubik was responsible for all the clinical neu- ropathology, in addition to a neurology prac- tice, until 1949 when he was joined by Dr. E. P. Richardson Jr. Dr. Kubik was known for his detailed approach to neuropathological materi- als, although he appeared to favor autopsy neu- ropathology over surgical neuropathology. Look- ing over his reports, one is impressed by their brevity, and the pathologists used to complain about the time it took him to sign out the more complicated (13). His Figure 17.2 In the Ether Dome, ca. 1960. Standing, careful approach was also ideal for training and left to right: Benjamin Castleman, Charles Kubik, Dr. Kubik trained a number of future leaders in Raymond Adams. Seated, second row: Robert Schwab, C. Miller Fisher, Philip Dodge, Ernest Picard. neuropathology, most notably Drs. Raymond Seated, third row: Maurice Victor, Shyam Pant Adams and E. P. Richardson. (probable), P. M. Dalal. In 1946, Dr. Kubik initiated the Tuesday after- noon Neuropathology Brain Cutting Conference early hours of Friday morning—and seen a satis- at the MGH. In this conference a case known to fying increase in attendance. the clinical staff that had come to postmortem A second important conference to which Dr. examination was fi rst presented in clinical detail Kubik and Neuropathology contributed was the and then discussed by the attendees, beginning weekly Clinicopathological Conferences (CPCs), with the medical students and proceeding to the held on Th ursdays in the historic Ether Dome most expert clinicians. Th e fi xed brain was then (fi gure 17.2). When the case to be presented was cut and the fi ndings analyzed in the context of of neurologic interest, Dr. Kubik participated the clinical picture. Th e remarkable utility of either as the neurologist who discussed the diff er- this exercise is that it allows all attendees, from ential diagnosis or as the neuropathologist who the neophyte to the expert, to attempt to local- demonstrated the fi ndings. He was known for ize the lesion anatomically on the basis of clinical being careful with his words and, as such, was signs and symptoms and generate a diff erential a superb teacher. Th e extraordinary care in the diagnosis as to the pathologic basis of the clinical workup of these cases and the quality of the dis- disease. Th is exceptional conference continues to cussion at these conferences is well illustrated in the present day as an essential component of the Neurological Clinicopathological Conferences, by MGH Neuropathology teaching program. For E. P. Richardson and Benjamin Castleman (14). the past three years it has been conducted in the Dr. Kubik held various appointments at

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Harvard Medical School, rising through the back to Harvard as Bullard Professor of Neuro- ranks to Associate Clinical Professor of Neurol- pathology and Director of the new Neurological ogy. He was not a prolifi c writer, but his care- Unit at Boston City Hospital. Th ere he continued ful approach to neuropathology contributed to his studies of neuropathology and neuroanatomy a series of important papers during his tenure, (21) until he was recruited, in 1934, to be the including the classic clinicopathological study of Chief of the fi rst Psychiatry Service at MGH— basilar artery occlusion that is still cited (15) and and to create the department. After he retired as the description of the lateral medullary infarct chief, Dr. Cobb returned to his long-term inter- (16). Dr. Kubik with Dr. Adams assembled an est in ornithology and comparative avian neuro- encyclopedic compendium of the pathology of anatomy, collecting and studying the brains of demyelinating diseases (17). Th is last publica- diff erent species of birds under the microscope. tion is notable for providing a classifi cation of He remains well known for his many contribu- this group of diseases and defi ning them by their tions to the fi eld of psychiatry and for his later preferential attack on myelin and myelin-form- interest in the environment, including a piece ing cells. Additionally, like Taylor’s earlier paper, entitled “Death of a Salt Pond,” published in the it provides outstanding clinical and pathological Cape Cod Times during his retirement. He died correlation (18). Other topics included a method in 1968. of removal of iodized compounds from the CSF (19) and of the nervous system (20). Charles S. Kubik: The Later Years In addition to directing the Neuropathology Dr. Kubik retired from his administrative duties Laboratory at the MGH, Dr. Kubik was active on in 1951. Dr. Adams succeeded him as Chief of the Neurology Service as a consultant attending Neurology, and Dr. E. P. Richardson Jr. took over . Dr. Adams, who was a junior resident the direct supervision of the Neuropathology at the MGH when he fi rst met Kubik in 1938, Laboratory at the MGH. Dr. Kubik remained said that Dr. Kubik had “one of the most astute on the staff as Senior Consultant in Neurol- minds in Neurology at the time” (13). Dr. Kubik ogy and Neuropathology, regularly working in also served as Chief of Neurology at the MGH the laboratory and pursuing his work in clinical from 1946 to 1951, after Dr. Ayer retired as chief. neurology for the next 20 years or so. In 1974 a Dr. Stanley Cobb, the Chief of Psychiatry at tribute to Drs. Kubik and Richardson was held the MGH from 1934 to 1955, was a major col- on the occasion of the overlapping meetings of laborator with Neuropathology during the Kubik the American Association of Neuropathologists era. Born in 1887, Cobb graduated from Harvard (AANP) (Dr. Richardson was President of the College in 1910 and HMS in 1914. After a surgical AANP that year) and the American Neurological internship at Peter Bent Brigham Hospital with Association (ANA) in Boston. Th is was possibly Dr. , he studied physiology for the last time that the ANA and the AANP met a year with Dr. William H. Howell and psychia- together. More than 140 alumni of the MGH try for two years with Dr. Adolph Meyer, both Neuropathology Laboratory attended this festive at Johns Hopkins University. Following Army occasion. Th e residents were particularly fond of service in World War I, he worked for four years recalling the yearly excursions to the Kubik home at MGH, followed by a two-year Rockefeller Fel- in Lincoln; they were invited to leave the ward lowship, which allowed him to study Neurology to go apple picking! Th roughout his long life, at Queen Square, as well as with Dr. Kubik was known to maintain a close focus in Paris, Cécile and Oskar Vogt in Berlin, and on whatever task was at hand; for example, in Sir Charles Sherrington at Oxford. He was called his eighties, he was said to have easily regained

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composure after falling from a ladder positioned (17), neoplasms (25), and metabolic diseases (26). precariously against a tree whose damaged limb He was the author of many books, including required hand-sawing. two textbooks on neuropathology (27, 28). Dr. Adams died in 2008, aged 98. From the s to the s: During his tenure as Chief of Neurology from The Era of Richardson, Adams, 1951 to 1977, Dr. Adams took MGH Neurol- and Fisher ogy from a small clinical department to a large, Neuropathology remained, along with most of partly subspecialized department involved in the rest of the anatomic pathology laboratories, extensive research activities. One of Dr. Adams’s in the Allen Street Building until the opening of key recruits in his early days was Dr. C. Miller the Warren Building in 1956. In 1957 the Neuro- Fisher, who joined the MGH Neurology Staff pathology Laboratory and the offi ces moved onto in 1954 (fi gure 17.3). Dr. Fisher was born in 1913 the second fl oor of the Warren Building, where and grew up in Manitoba. He graduated from they would remain through 1977. the University of Toronto Medical School in As mentioned above, Dr. Raymond Adams 1938. After internship and a year of in became Chief of the Neurology Service at MGH medicine, he joined the Royal Canadian Navy in 1951 (fi gures 17.2, 17.3, and 17.4). Dr. Adams in World War II. His ship was torpedoed in the was a remarkable individual who is considered Atlantic, and he spent the rest of the war as a the most infl uential academic neurologist of the prisoner in Germany (1940–1945). After the war, second half of the twentieth century (13). He was a native of Oregon and graduated from the new Duke University Medical School in 1936. Follow- ing a Rockefeller to study neurology at the MGH and psychiatry at Yale, he moved to Boston City Hospital to train in neurology and work with Dr. Derek Denny-Brown. It was dur- ing his tenure at Boston City Hospital that his interest in neuropathology began and fl ourished. Dr. Adams considered himself as much a neu- ropathologist as a neurologist, and the authors recall sitting with him reviewing microscopic specimens when he was well into his eighties. His emphasis on the neuropathological basis of neu- rological disease was also imprinted on all of his many trainees over the decades, to the extent that all MGH Neurology residents spent a full year of their three residency years studying neuro- pathology. His many contributions to the fi elds were based to a large extent on his combination of clinical and neuropathological expertise. Th e breadth of his interests in neuropathology was wide, extending from muscle disease (22, 23) Figure 17.3 E. P. Richardson (foreground), Miller to peripheral disease (24) to neurodevel- Fisher, and Raymond Adams (standing) poring over a opmental disorders, demyelinating conditions brain in the Warren basement, ca. 1976

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Figure 17.4 Neuropathology, 1968–1969. Front row, left to right: Eileen Ouellette, Margaret Norman, Raymond Adams, Charles Kubik, E. P. Richardson, Elizabeth Dooling. Second row: Karl Åström, Richard Baringer, Donald Price, Horatio Aldredge, William Schoene. Th ird row: Surl Nielsen, Edward Wolpow, Fred Cantor, Walter Bradley, Henry Schmidek, Robert Ackerman.

he returned to Montreal as a Fellow in Neurology wearing a watch after his wartime experiences), at the Montreal Neurological Institute, spend- his late nights and weekends examining ing much of his time in neuropathology. He in extraordinary detail, and his interest in “serial then spent a year as a fellow at Harvard before sections” of histological material, notably blood returning to the Montreal Neurological Institute vessels. Well into his eighties, he would come as Neuropathologist and Lecturer in Neurol- to the weekly Neuropathology Brain-Cutting ogy for four years. He was appointed Neurolo- Conferences, weigh the clinical details carefully, gist and Associate Neuropathologist at MGH point out the lack of primary description of the in 1954 and Consultant in Neuropathology in clinical signs, opine at length on the likely diag- 1984, resigning in 2005, when he was over 90. nosis (nearly always arriving at the correct one), His tenure was characterized by his astounding and then make suggestions on how further care- to detail and his near-total recall, which ful analysis of the ’s clinical history and seemed to involve every patient and every brain signs and more detailed examination of the brain he had ever examined. He was renowned for his (usually with serial sections!) might yield unique lack of interest in time (manifested by his never insights on the case. Th ese skills made Dr. Fisher

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a pioneer in careful clinicopathological correla- Drs. Adams and Fisher, was gifted in his abili- tion in the fi eld of neurovascular diseases, and his ties to correlate the clinical and neuropathologi- work is considered by many to have heralded the cal details of neurological disease. His dominant modern era of understanding (16, 29). role as the neuropathologist at MGH during the Dr. E. P. Richardson Jr., known universally as rapid expansion of the Neurology Service and its “E.P.,” rejoined the Neuropathology Laboratory training programs provided him an unparalleled in 1949, after a sojourn at Queen Square with opportunity to work with some of the brightest J. G. Greenfi eld, took over its direction from Dr. young academic neurologists of his time. His Kubik in 1951, and remained the primary neu- patience in teaching, long remembered by all ropathologist at MGH through the 1980s and who trained with him, made him an ideal edu- a faculty member in Neuropathology until his cator. As the quote at the start of this chapter death in 1998 (fi gures 17.3 through 17.6). Origi- demonstrates, Dr. Richardson was excited by the nally trained in neurology and psychiatry, he study of neuropathological processes. His con- continued a limited clinical practice in neurol- tributions to the fi eld are extensive and wide- ogy, which included attending on the wards for a ranging and are discussed in chapter 11. month each year until 1982. Dr. Richardson, like Dr. Richardson ran the clinical service for

Figure 17.5 Neuropathology, 1985. Front row, left to right: Neil Kowall, E. P. Richardson, Cecil Treip, Tessa Hedley- Whyte, Raymond Sobel. Second row: Dana Gabuzda, Dora Hsu (technologist), Robert Ferrante (chief technologist), Susan Smith (secretary), Lu Ning Wang (research fellow). Back row: Suzanne de la Monte, Bruce Hamaty (technologist), Margie Hodges (secretary), Holly Goolsby (technologist).

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Figure 17.6 E. P. Richardson’s eightieth birthday celebration, 1998. Left to right: Umberto De Girolami, Margie Hodges (secretary), Jean Paul Vonsattel, Kettelie Allien (secretary), Kathy Newell, Peggy Richardson, Robert Colvin, E. P. Richardson, Maria Ullian (technologist), Tessa Hedley-Whyte, Suzanne de la Monte, Holly Goolsby (technologist), Dora Hsu (technologist), Matthew Frosch, David Louis.

many decades, with help primarily from the and there were approximately 500 per trainees. Dr. Karl Erik Åström worked closely year. Th e types of case material examined in the with Dr. Richardson as a member of the service laboratory varied during this period. Review of from 1966 to 1979 (30) (fi gure 17.4). Dr. George the autopsy volumes shows the epidemic of M. Kleinman, a graduate of the program, was the 1950s, and the experience with developmen- Assistant Neuropathologist from 1977 to 1981, tal disorders from 1956 to 1980, when the labo- during which time he participated in the Child- ratory was responsible for the autopsies on the hood Consortium (see below). decedents at the Wrentham, Paul A. Dever, and Dr. Kleinman later joined the faculties at New Walter E. Fernald state schools. In the 1950s and York University and then Mount Sinai School of 1960s many cases were sent to Dr. Paul Yakovlev Medicine. in the Warren Museum at HMS for whole brain Neuropathology was busy during this period: embedding in celloidin and serial sectioning, and the number of surgical neuropathology specimens many of Dr. Yakovlev’s sections still reside on increased, from 139 neurosurgicals (including 32 Warren 3. muscle biopsies and 11 nerve biopsies) in 1956 to During this time, Neuropathology was actively 204 (including 49 muscle and 43 nerve) in 1966, supported by Dr. Benjamin Castleman, who

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served as the Chief of the Pathology Service from 1952 through 1974. Nonetheless, Neuropathol- ogy was considered quite distinct from the rest of Pathology, and Anna Castleman was surprised, upon meeting David Louis in 2009, to hear that a “neurologist” had been appointed Chief of Pathology in 2006. Dr. Raymond Adams established the separate Experimental Neuropathology Laboratory as part of the Neurology department, under his and Dr. Fisher’s direction. Th is laboratory was originally on the fourth fl oor of the Bulfi nch Building, later moving to the seventh fl oor of the Vincent Burn- ham Kennedy Building. Th is was the initial sup- porting laboratory for the Brain Bank in the early days of the Massachusetts Alzheimer’s Disease Research Center (MADRC), in the mid-1980s. From the s to the Present Day Dr. E. Tessa Hedley-Whyte was recruited to MGH Pathology from New England Deaconess Hospi- tal in 1981 (fi gure 17.7). She was born in London, England, in 1937, grew up in Newcastle-upon- Figure 17.7 E. Tessa Hedley-Whyte, Director of Tyne, and graduated from the University of Dur- Neuropathology, 1989–2007, in 2007. ham Medical School, in Newcastle-upon-Tyne, in 1960. She began a pathology internship in was also a part-time neuropathologist at both 1960 at Boston’s Children’s Hospital under the Peter Bent Brigham (1968–1971) and Beth Israel tutelage of Drs. Sidney Farber and Gordon Vaw- hospitals (1971–1977), as well as consultant to ter, followed by a year each at New England Dea- New England Deaconess Hospital. In 1977 Dr. coness and Peter Bent Brigham hospitals with Hedley-Whyte joined the Pathology staff at New Drs. William A. Meissner and Gustave Dammin. England Deaconess and Baptist hospitals as an After six months of training in neuropathology anatomic and neuropathologist and then moved at Children’s Hospital with Dr. Floyd H. Gilles to the MGH in 1981 (31). Dr. Hedley-Whyte was and six months of fetal and obstetric pathology named head of Neuropathology in 1988, becom- with Drs. John Craig and Shirley Driscoll, Dr. ing the third director of the Neuropathology Hedley-Whyte became a research fellow with Dr. Laboratory at MGH and the fi rst pathologist- Betty Geren Uzman, an early pioneer of applied neuropathologist to hold this post. Th is change electron microscopy and the study of myelina- coincided with a national shift in the numbers of tion of peripheral nerve at the Children’s Can- neuropathologists who were originally trained as cer Research Foundation. Dr. Hedley-Whyte was neurologists to those originally trained as pathol- recruited to the staff of Children’s Hospital to ogists. As a result, nearly every faculty neuropa- develop the Electron Microscopy Unit and estab- thologist appointed after 1981 has been a pathol- lish a research program for the Mental Retarda- ogist-neuropathologist (with the exception of Dr. tion Center in 1967. During the next 10 years she Ann McKee; see below). Th is trend coincided

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with a gradual decrease in the amount of time laboratory moved up one fl oor in 1977 to the spent by neurology residents in neuropathology third fl oor of the Warren Building, where the training, from the one full year under Dr. Adams offi ces have remained to the present day. Th at progressively down to the current two months. location put Neuropathology next to the Neu- Dr. Hedley-Whyte’s interests, like Dr. Rich- rology and Neurosurgery research laboratories ardson’s, have been broad within the fi eld of (Drs. Shirley Wray, Adelbert Ames III, Robert neuropathology, and her specifi c emphases are H. Brown Jr., Stephen Hauser, Marian DiFig- on myelin formation, blood-brain barrier altera- lia, among others) and the Neurology Electron tions, prognostic factors in brain and pituitary Microscopy (EM) Unit. Th e EM unit had been tumors, and neurodegenerative diseases (32– established by Humberto Fernandez-Moran (bio- 39)—many of these studies in collaboration with physicist in Neurosurgery at MGH, 1959–1962). her longtime research assistant, Dora Hsu, M.Sc. Th is unit was later directed by Dr. Harry deF. Dr. Hedley-Whyte’s contributions to the teach- Webster, and subsequently by Drs. Dennis Lan- ing programs, as Training Program Director for dis and John Halperin; it undertook the ultra- both Pathology (1985–1996) and Neuropathology structural analysis of all nerve, muscle, and brain (1988–2007), have been exemplary, as have been biopsies. In the early 1980s, when Dr. Landis left, her talents as an astute observer and her extraor- the Zeiss-9 electron microscope and technician dinary devotion to the teaching of neurology and (Holly Goolsby) were transferred to Neuropa- pathology residents as well as neuropathology fel- thology. In 1993 the ultrastructural examination lows (fi gures 17.5, 17.6, and 17.8). Th ree of her of neuropathological specimens was combined fellows have become chairs of academic pathol- with the rest of diagnostic electron microscopy ogy departments and one has been a Dean. Dr. in the Pathology Department EM unit on Cox 5. Hedley-Whyte’s many national activities include In 1998 the Neurohistology Lab was closed down 12 years of service as Moderator of the Annual after 70 years and its responsibilities merged into Diagnostic Slide Session of the AANP. the new departmental Histology Laboratory on Other primary clinical faculty and their research Blake 3. And in 1999 Dr. Hedley-Whyte’s research interests during this time included George Klein- laboratory on Warren 3 closed, and Warren 3 was man (1977–1981, brain tumors); Raymond A. remodeled again to accommodate the Clinical Sobel (1982–1992, demyelinating diseases); Jean Electron Microscopy Unit, which moved from Paul Vonsattel (1988–2001, Huntington’s disease Cox 5 to Warren 3 in 2000. and brain banking); Suzanne de la Monte (1987– Surgical neuropathology practice grew during 1999, AIDS and Alzheimer’s disease); Ann McKee this time, while the number of autopsy brains (1991–1994, neurodegenerative diseases); David decreased, in parallel with national trends. For N. Louis (1991–present, brain tumors); Matthew example, yearly neurosurgical specimens were P. Frosch (1994–present, neurodegenerative dis- approximately 700 in 1981 but had risen to 1,029 eases); Anat O. Stemmer-Rachamimov (2002– by 2009. On the other hand, postmortems with present, hereditary brain tumor syndromes); Di brain examination numbered 400 in 1980 but Tian (2009–present, ). Faculty appointed only 187 in 2009; and nerve and muscle biopsies on a consultative or temporary basis has included totaled about 360 in 1980 but had dropped to 156 Drs. Hannah Kinney (1982–1992) and Matthew in 2009. Th e sequential numbering of the autop- Anderson (1999–2002). sies (begun in 1896) came to an end at 46,054 Th is period witnessed many changes in loca- with the introduction of a new anatomic pathol- tion and affi liation of diff erent components ogy laboratory information system, CoPath, in and personnel. Th e Neuropathology offi ces and 1990. In 2004, with the change to another system

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(PowerPath), the neuropathological part of each are still in use today. Th e Brain Bank was ini- autopsy was given a separate accession number. tially a freezer in Dr. Growdon’s laboratory, and Th e increase in neurosurgical specimens was staff ed by Olgerts Zvaigzne, a histotechnologist accompanied by a growth in the neuro- in the Experimental Neuropathology Labora- practice at MGH. An informal neuro-oncology tory; both labs were on Burnham Kennedy 7. A conference had been established in the mid-1980s small laboratory on an upper fl oor of the War- by Drs. Rita Linggood of Radiation Oncology, ren Building, with its own histotechnologist, was Robert Ojemann and Paul Chapman of Neuro- acquired for histology about 1987; around 1991 , and Dr. Hedley-Whyte of Neuropathol- the lab moved to larger quarters on Burnham 8. ogy. A formal adult brain tumor management When Dr. Jean Paul Vonsattel became codirector conference was established with the foundation of the MADRC Brain Bank in 1996, he was able of the Brain Tumor Center at MGH in the early to improve its procedures signifi cantly using his 1990s. A pediatric brain tumor conference was experience with the Brain Tissue Resource Cen- established when Dr. Nancy Tarbell became Chief ter at McLean Hospital (40). With the opening of of Pediatric Radiation Oncology in 1997; the the Center in Building 149 in 1991, emphasis was on whether children would derive Dr. Vonsattel became Director of the Molecular particular benefi t from proton beam as opposed Neuropathology Laboratory and the Associate to conventional radiotherapy. Th e neuropatholo- Director of the Brain Tissue Resource Center gists have maintained a strong presence at both at McLean, where he was able to continue his of these important clinical management confer- research into Huntington’s disease and develop ences, and the Neuropathology fellows play a key his brain banking procedures. When the Cen- role in presenting and discussing fi ndings. ter for the Study of Neurodegenerative Diseases Th e period also saw an increase in the amount moved into the newly renovated Building 114, of grant-funded research activities in Neuropa- the MADRC Brain Bank moved from Burnham thology, focused primarily on neurodegenerative 8 to the third fl oor of Building 114, where it had diseases and on brain tumors. Dr. Hedley-Whyte two dedicated rooms, one for dissection and one was a coinvestigator of the Childhood Brain for histology, as well as an offi ce for the database Tumor Consortium (Dr. Floyd Gilles, Chil- manager–histologist (Karlotta Fitch since 1991) dren’s Hospital Boston, was the principal inves- and an offi ce for Dr. Vonsattel. Th e fellowship tigator). Drs Richardson, Hedley-Whyte, Sobel, funding from the MADRC has proven impor- and Kleinman of the MGH were “slide readers” tant for the training program: of a total of 20 in this project, reading slides from more than MADRC Neuropathology fellows to date, seven 3,000 pediatric brain tumors from fi ve North are involved in research of neurodegenerative dis- American institutions (37–39). Th e MADRC orders and 16 are in academic neuropathology. was established in 1984, Dr. John Growdon of Dr. Raymond A. Sobel arrived at the MGH Neurology serving as the principal investigator. in 1981 as a research fellow in with A compulsory condition of this grant was the Drs. Robert Colvin and Robert McCluskey, hav- establishment of a neuropathology core, includ- ing completed neuropathology training at Stan- ing a brain bank. Dr. Hedley-Whyte was the ford University Medical School with Dr. Lucien principal investigator of this core from its start in Rubinstein (fi gures 17.5 and 17.8). He joined the 1984 until 2007. Importantly, the core included faculty in 1982 and had an active research pro- funds for a Neuropathology fellow. Th e fi rst fel- gram exploring the mechanisms of demyelinat- low was Dr. Suzanne de la Monte, who set up ing diseases (41–44). He returned to Stanford in the management systems for these studies, which 1992 to continue his work on

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and , becoming Professor of pathology before joining the faculty in 1988. Pathology and then Editor of the Journal of Neu- His grading of the neuropathological changes in ropathology and . Huntington’s disease brains has been signifi cant Jean Paul Vonsattel, a graduate of the Uni- in the study of this condition (45, 46). He also versity of Lausanne, came to the MGH as a had a long-standing interest in amyloid angiopa- research fellow with Dr. Richardson in 1981 thy (47). Dr. Vonsattel became Professor of Neu- and was assigned to the Brain Bank of the new ropathology and Director of the New York Brain Huntington’s Disease Center without Walls at Bank at Columbia University in 2001. McLean Hospital (fi gures 17.6 and 17.8). He later Dr. Suzanne de la Monte commenced her became a clinical fellow and resident in anatomic neuropathology training with Dr. Richardson in

Figure 17.8 Celebration in honor of E. Tessa Hedley-Whyte, with her colleagues and trainees in front of the Bulfi nch Building, November 2007. Front row, left to right: Leroy Sharer, David Louis, Joseph B. Martin, Tessa Hedley-Whyte, John Hedley-Whyte, Matthew Frosch, John M. (Jack) Lee. Second row: Kathy Newell, Joe Ma, Raymond Sobel, Shirley Wray, Anat Stemmer-Rachamimov, Hannah Kinney, Douglas Miller, Rolf Pfannl, Robert Colvin, Jeff rey Golden. Th ird row: Stefanie Freeman, Karlotta Fitch, John Henson, Alyssa Lebel, Verne Caviness, Elizabeth Engle, Ann McKee, Jonathan Horton. Fourth row: Pavan Auluck, Krishan Krishnamurthy, Hart Lidov, Je Eun Kim, Elizabeth Lee-Lewandrowski, Ivana Delalle, Nancy Harris, David Cardozo, Rebecca Folkerth, Suzanne Mirra. Fifth row: Di Tian, Michael Lawlor, Pornsook (Mint) Cheonchun, Lester Adelman, Bradley Hyman. Sixth row: Christopher William, Matija Snuderl, Th or Stein, Elizabeth Dooling, Holly Goolsby, Jean Paul Vonsattel, Robert Brown.

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Figure 17.9 MGH Neuropathology faculty, 2010. Left to right: Tessa Hedley-Whyte, Di Tian (standing), Matthew Frosch (Director of Neuropathology 2007–), Anat Stemmer-Rachamimov (standing), David Louis.

1984 and joined the faculty in 1987 (fi gures 17.5, utility of molecular genetic approaches in subdi- 17.6). Dr. de la Monte’s research included investi- viding malignant into clinically relevant gations into neurodegenerative diseases; she was entities. He showed that the loss of chromosomes involved in setting up the MADRC Brain Bank 1p and 19q in anaplastic was databases. She has also investigated the eff ects of associated with a better overall survival and pre- AIDS on the brain (48–50). She became Profes- dicted a better response to chemotherapy. His sor of Pathology, Medicine and Neuroscience at important contributions to our understanding Brown University in 1999. of the role of molecular alterations in the genesis Dr. David N. Louis (chapter 25) completed and behavior of gliomas have been recognized his training in Anatomic and Neuropathology at by his numerous awards and his invitations to the MGH in 1991, and in 1992 he took over the author and edit the World Health Organization Molecular Neuro-Oncology Laboratory (fi gures classifi cation of brain tumors as well as Green- 17.6, 17.8, and 17.9). Dr. Louis’s work in brain fi eld’s Neuropathology and other neuropathology tumors grew out of the seminal studies done by references (11, 51–53). Dr. James Gusella and his fellow, Dr. Bernd Seiz- Dr. Matthew P. Frosch, after completing his inger, in linking genes responsible for hereditary training at Brigham and Women’s Hospital, brain tumor syndromes, such as the neurofi bro- joined the MGH faculty part-time in 1994 and matoses. Dr. Louis went on to demonstrate the full-time in 2002 (fi gures 17.6, 17.8, and 17.9).

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His particular interests have been in neurodegen- colleagues celebrated her contributions at MGH erative disease and amyloid angiopathy, including (fi gure 17.8). animal models of these diseases (54–56). Frosch attended Amherst College and HMS, graduat- Educational Activities ing with an M.D. and Ph.D. from the combined MGH Neuropathology has always been involved Harvard and MIT Health Sciences and Technol- in extensive educational activities involving ogy (HST) program in 1987. Dr. Frosch is the medical students, residents, fellows, and practic- Lawrence J. Henderson Associate Professor of ing physicians. In particular, the residency and Pathology and HST at MIT and is responsible fellowship programs have trained hundreds of for the teaching of neuroanatomy to the HST neuropathologists, neurologists, pathologists, students. Since 2008 he has run the admissions and neurosurgeons, and more than 200 train- process for the HST program. In addition, he is ees have spent extended periods in the division. the faculty coordinator for the tissue-based activ- All together, the training program has produced ities of the Harvard NeuroDiscovery Center. approximately 50 practicing neuropathologists, Dr. Anat Stemmer-Rachamimov was born in addition to many part-time neuropathologists in Israel, lived in Iran, and obtained her medi- and a number of chairs of neurology and pathol- cal degree from the University of Milan in 1982 ogy departments. (fi gures 17.8, 17.9). She received her training in Depending on which source you believe, the pathology at the University of Newfoundland fi rst recognized trainee in neuropathology at and in neuropathology in London, Ontario, MGH was either Walter Igersheimer in 1944, in before joining David Louis as a research fellow the newly established position of Research Fel- in tumor in 1997. She joined the MGH low in Neuropathology (according to Tracy Mal- faculty in 2001 and became Associate Director of lory’s 1944 annual report), or Dr. Mary Lorraine Ophthalmic Pathology in 2008. Her research area Gannon in 1947 (according to E. P. Richardson is the molecular and genetic biology of Schwann [1] and Nathaniel Faxon [59]; however, the fi rst cells, neurofi bromatosis, and mention of Gannon in the bound autopsy vol- analysis of animal models of these diseases and umes is as a resident in Neuropathology in 1949). other inherited tumor syndromes (57, 58). One of the autopsy volumes for 1949 also lists Dr. Di Tian was born in China and obtained a fellow in Neuropathology, Dr. Rafael Estrada his from Beijing Medical College from Cuba. Another early mention of a neuro- in 1992 and his Ph.D. from Northwestern Uni- pathology trainee in the autopsy volumes is in versity in 1998 (fi gures 17.8 and 17.9). After com- September 1951: Dr. Lysia Saxe (later Forno) is pleting anatomic and neuropathology training listed as clinical fellow in Neuropathology, and at the MGH, he joined the faculty in 2009. His Dr. Remedios (Rose) Rosales is listed as Neuro- research area is the cellular and molecular origins pathology resident. Some of the early trainees of autism. became full-time neuropathologists; in addi- A major administrative change took place tion to Lysia Forno and Remedios Rosales, these in 2006, when David Louis became the sixth include Lowell Lapham, Françoise Robert, Harry Chief of the Pathology Service—the fi rst neu- Webster, George Collins, and Betty Q. Banker. ropathologist to occupy the position. And, in In the 1950s and early 1960s most trainees 2007, Matthew Frosch succeeded Tessa Hed- came from Neurology and Psychiatry and all the ley-Whyte as Director of Neuropathology. In Neurology residents spent at least one full year November of that same year, a gathering of Dr. in Neuropathology. In 1967 the fi rst pathologist Hedley-Whyte’s current and former trainees and was accepted for training with Dr. Richardson,

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Virgilio Sangalang from Halifax, Nova Sco- program is accredited for three trainees per year, tia. Many of the residents were supported by a and since 1982 the program has graduated 23 training grant in neuropathology administered board-certifi ed neuropathologists, all but two of by Drs. Adams and Richardson, including indi- them now practicing full-time neuropathology. viduals who went on to successful academic In 1995 a two-month exchange of neuropa- careers in neuropathology, such as Drs. Arthur thology fellows was arranged between Chil- Asbury, Byron Kakulas, Donald Price, Virgilio dren’s Hospital/Brigham and Women’s Hospital Sangalang, William Schoene, Surl Nielsen, Colin Neuropathology and the MGH Neuropathol- Masters, Margaret Norman, Herbert Schaum- ogy training programs so that the MGH fellows burg, Umberto De Girolami, Peter Johnson, could gain additional experience with fetal and Henry Powell, and John Trojanowski. After Dr. pediatric pathology, and the Children’s Hospi- Joseph B. Martin succeeded Dr. Adams as Chief tal/Brigham and Women’s Hospital residents of Neurology in 1978, the neurology residents’ could study material from the MADRC. In 2010 experience in Neuropathology was decreased to this rotation was reduced to one month, as the six months; later, as the number of residents in fetal and neonatal experience at MGH had been the neurology training program increased, it was greatly augmented by the return of an obstetri- further reduced to four months and, in 1999, to cal service in 1999. Experience in forensic neuro- two months. pathology had been gained at MGH itself until Although the MGH had long had a robust the mid-1980s, as all trauma and burns deaths at training program in neuropathology, the Accred- MGH were autopsied at the hospital on behalf itation Council for Graduate of the Medical Examiner. After that time, the (ACGME) did not begin separate accreditation Medical Examiner took cases to the offi ce near of neuropathology training programs until 1971. Boston City Hospital, where the brains were cut Dr. George Kleinman commenced the paperwork by Dr. Th omas Kemper, and the neuropathology for formal accreditation of the MGH program fellows had to go to Boston City to participate in in 1980, and Dr. Hedley-Whyte completed the these brain cuttings. Dr. Hedley-Whyte became a application with Dr. Richardson as the Program consultant to the Medical Examiner in 2007 and Director and Dr. Hedley-Whyte as codirector. takes the fellows twice a month to learn forensic Accreditation was granted in 1982 for two trainees neuropathology. per year in a two-year program, although hospi- One of the traditions of the teaching program tal funding was available for only one trainee per that has existed since Charles Kubik’s time is year. Dr. Douglas C. Miller was the fi rst trainee the weekly evening Mystery Case Conference. in the offi cially accredited program. Beginning in According to E. P. Richardson, this was insti- 1990, the program began to accept a new resident tuted while he was a trainee as a dedicated time each year instead of every other year, funding for the residents to spend with Dr. Kubik when coming the second year through the MADRC. he would not be seeing patients. Th is conference Th is enabled trainees to undertake more in-depth was later directed by Dr. Adams and Dr. Rich- research projects as well as to gain broad experi- ardson, and attended by Dr. Fisher and all the ence of the neurodegenerative disorders. In 1995 neurology trainees on rotation in Neuropathol- Dr. Richardson and his wife established the E. P. ogy. Th is session was suffi ciently highly regarded Richardson, Jr. Fellowship in Neuropathology, in the 1960s that Dr. Floyd Gilles from Children’s which has enabled fellows to pursue additional Hospital, Boston, was also a regular attendee. It years of research following their residencies; Dr. continues in a robust manner to the present day, Kathy Newell was the fi rst fellow. Currently the although it no longer includes the traditional

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supper and gossip in the cafeteria before viewing by Drs. S. Love, Louis, and D. Ellison (11), the the slides. 2007 World Health Organization Classifi cation Th e program has also participated in HMS of Tumours of the , edited courses for many decades. From at least 1956 until by Drs. Louis, H. Ohgaki, O. Wiestler, and W. the late 1960s, MGH Neuropathology trainees Cavenee (52), and the Armed Forces Institute of attended the evening course in neuroanatomy, Pathology fascicle Non-Neoplastic Diseases of the , and pathology of the nervous Central Nervous System by Drs. Louis, Frosch, system directed by Dr. Paul Yakovlev and later H. Mena, E. Rushing, and A. Judkins (61). Drs. by Drs. Richard L. Sidman and Merrill K. Wolf Frosch and De Girolami have also authored mul- at HMS. Moreover, the Neuropathology trainees tiple editions of the nervous system chapter in and faculty have also played a strong role in the Robbins and Cotran Pathological Basis of Disease, teaching of neuroanatomy and neuropathology and Drs. Louis, Frosch, Hedley-Whyte, and at HMS. Dr. Stanley Cobb, Chief of Psychiatry Sobel contributed chapters to the 2004 edition at the MGH, was responsible for the medical of Escourolle and Poirier’s Manual of Basic Neu- student teaching of neuroanatomy and neuro- ropathology (edited by F. Gray, U. De Girolami, pathology, followed by Dr. Adams. Drs. Adams, and J. Poirier) (62). Alfred Pope, and Richardson conducted a six- week course in neuropathology for HMS stu- National Leadership dents from the 1950s until 1968, which was well Th e successes of MGH Neuropathology over the received by the Neuropathology trainees (13, 27). years have also been demonstrated by national Th is course was off ered for the next few years as leadership in the fi eld. For example, Drs. Adams an advanced one-month elective neuropathology (1955), Richardson (1974), Hedley-Whyte (1996), course by Drs. Richardson and Pope. Dr. Rich- and Louis (2010) all served as President of the ardson was an active participant in the design American Association of Neuropathologists, of the “Human Nervous System and Behavior” and Drs. Adams (1979), Richardson (1988), and course in the HMS New Pathway program in the Hedley-Whyte (2005) each received the Ameri- late 1970s; this course was redesigned in 1987 with can Association of Neuropathologists’ Award for the help of Drs. Richardson and Hedley-Whyte. Meritorious Service. Further, Drs. Lysia Forno All members of the staff and trainees continue to (1991; trainee in 1951), Lowell Lapham (1994; teach in the in both the standard trainee in 1954), Henry deF. Webster (2001; HMS and the HST programs. David Louis was trainee in 1956), and Margaret Norman (2008; the HST Neuroanatomy Course Director from trainee in 1968) were also recipients of this award. 1994 to 2001 and was succeeded by Matthew Other graduates who have served as President of Frosch, who continues in this role. the American Association of Neuropathologists Other educational activities of the MGH include Drs. Webster, Donald Price, John Tro- Neuropathology group have included extensive janowski, and Jeff rey Golden. Dr. Webster also participation in the MGH Case Records (chap- served as President of the International Society of ter 24). For example, members of the group were Neuropathology. the pathologist discussants in approximately 100 CPCs between 1981 and 2010. Th e group has also Conclusion edited or written a number of major textbooks, Th e lineage of MGH Neuropathology can be including Pathology of Peripheral Nerve by Drs. traced from the great British and European Richardson and De Girolami (60), the eighth neuropathologists of the late nineteenth and edition of Greenfi eld’s Neuropathology, edited early twentieth centuries and from the earliest

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neurologists at Harvard, through Drs. Kubik, 13. Laureno R. Raymond Adams: A Life of Mind and Richardson, and Hedley-Whyte, and to the neu- Muscle. New York: Oxford University Press, 2009. ropathologists of today. Th e future of MGH Neu- 14. Richardson EP Jr., Castleman B, eds. Neurologi- ropathology promises to be even brighter than its cal Clinicopathological Conferences. Boston: Little, past. It is a vibrant department, busy with clini- Brown, 1968. cal cases and populated by young physicians and 15. Kubik CS, Adams RD. Occlusion of the basilar artery. A clinical and pathological study. Brain physician-scientists who have superb clinical and 69:73–121, 1946. experimental training. With the armamentarium 16. Fisher CM, Karnes WE, Kubik CS. Lateral med- of neuropathology now greatly expanded beyond ullary infarction. Th e pattern of vascular occlu- the light and electron microscopes, MGH Neu- sion. J Neuropathol Exp Neurol 20:323–379, 1961. ropathology is poised to continue its tradition of 17. Adams RD, Kubik CS. Th e morbid anatomy of disease description and discovery. the demyelinative diseases. Am J Med 12:510–546, 1952. References 18. Taylor EW. Zur pathologischen Anatomie der 1. Richardson EP Jr. Neuropathology Laboratory. multiplen Sklerose. J Neurol 5:1–6, 1894. Th e News, Massachusetts General Hospital, 1–8, 19. Kubik CS, Hampton AO. Removal of iodized oil 1957. by . N Engl J Med 224:455–457, 2. Ayer JB, Viets HR. Edward Wyllys Taylor. Arch 1941. Neurol Psych 28:1182–1187, 1932. 20. Kubik CS, Richardson EP Jr., Donaghy RM. Brain 3. Taylor EW. Poliomyelitis of the adult. J Nerv abscess. Trans Am Neurol Assoc 56:121–126, 1951. Ment Dis 29:449–480, 1902. 21. Gildea MC, Castle WB, Gildea EF, Cobb S. Neu- 4. Taylor EW. Four Defective Brains. J Bost Soc Med ropathology of experimental vitamin defi ciency. A Sci 1:10, 1897. report of four series of dogs maintained on diets 5. Harvard University. Reports of the President and the defi cient in the . Am J Pathol 11:669– Treasurer of Harvard College. 1912–1913. Th e Medi- 680 3, 1935. cal School 3171, http://pds.lib.harvard.edu/pds/ 22. Adams RD, Denny-Brown D, Pearson CM. Dis- view/2574586?n=3171, 1913. eases of Muscle: A Study in Pathology. 1st ed. New 6. Wright JH. Unusual degeneration of the spinal York: Hoeber, 1953. cord. J Bost Soc Med Sci 1:10–11, 1897. 23. Walton JN, Adams RD. Polymyositis. Edinburgh: 7. Councilman WT, Mallory FB, Wright JH. Cere- Livingston, 1958. bro-spinal and its relation to other 24. Asbury AK, Arnason BG, Adams RD. Th e infl am- forms of meningitis. J Bost Soc Med Sci 2:53–57, matory lesion in idiopathic polyneuritis. Its role in 1898. pathogenesis. Medicine 48:173–215, 1969. 8. Richardson O. Friedreich’s ataxia. J Bost Soc Med 25. Schaumburg HH, Plank CR, Adams RD. Th e Sci 3:25, 1898. reticulum cell sarcoma-microglioma group of 9. Wright JH. Neurocytoma or neuroblastoma, a brain tumours. A consideration of their clinical kind of tumor not generally recognized. J Exp features and . Brain 95:199–212, 1972. Med 12:556–561, 1910. 26. Victor M, Adams RD, Collins GH. Th e Wernicke- 10. Greenfi eld JG, Meyer A, Norman RM, McMen- Korsakoff Syndrome: A Clinical and Pathological emy W, Blackwood W, eds. Neuropathology. Lon- Study of 245 Patients, 82 with Post-Mortem Exami- don: Edward Arnold, 1958. nations. Philadelphia: F. A. Davis, 1971. 11. Love S, Louis DN, Ellison DW, eds. Greenfi eld’s 27. Adams RD, Sidman RL. Introduction to Neuropa- Neuropathology. 8th ed. London: Hodder-Arnold, thology. New York: Blakiston Division, McGraw- 2008. Hill, 1968. 12. Peiff er J. [One hundred years of German neuro- 28. Haymaker W, Adams RD. Histology and Histo- pathology] (German). Pathologe 18 Suppl 1:S21– pathology of the Nervous System. Springfi eld, Ill.: S32, 1997. Th omas, 1982.

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