Chapter Neuropathology 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- disease process, and as to its nature. Th e cells ogy subspecialties at the MGH, it is the oldest, in and fi bers that are disclosed by the microscope terms of both dedicated subspecialty 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 Neurology and later Neurosurgery, 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 nervous system 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 230 pathology_chap17.indd 230 8/16/11 10:21 AM Neuropathology 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 autopsy studies. how refi ned. Th is, too, we must know. Dr. Edward Wyllys Taylor trained in neuropa- thology in Berlin with Hermann Oppenheim 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: Pathology 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 neuron death rather than direct neuropathology research was collaborative infection of the neurons themselves, and he made with other individuals and departments, nota- it clear that this was a controversial issue; none- bly Dr. Stanley Cobb in Psychiatry 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 Brains” (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 Medical School (HMS). He had studied degeneration of the spinal cord, in which there 231 pathology_chap17.indd 231 8/16/11 10:21 AM Keen Minds to Explore the Dark Continents of Disease 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 neuroanatomy (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 ataxia 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 brain such as medulloblastomas (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 Percival Bailey, who described it in medulloblastoma. Th e clinical chemistry 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 neurosyphilis. 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.