Should football be illegal?

Two neuropathologists are prominently spotlighted in an article by Malcolm Gladwell in the October 19 issue of The New Yorker. The article explores a provocative question raised by autopsy results on football players: namely, should football be illegal? Featured are Dr. Ann McKee (pictured), neuropathologist at the Veterans Hospital in Bedford, Massachusetts and Dr. Bennet Omalu, forensic neuropathologist and San Joaquin Valley (CA) chief medical examiner. Drs. McKee and Omalu have done some interesting autopsy work which suggests that the tau-positive chronic traumatic encephalopathy suffered by football players is much more common, even among high school players, than previously realized. As an example, McKee provides photomicrographs from a case of an 18-year-old high school football player and says: "He's got all this tau. This is frontal and this is insular.... This is completely inappropriate. You don't see tau like this in an 18-year-old. You don't see tau like this in a fifty year old."

You might counter that this is simply the result of a few bad-luck hits on the field, but research involving the University of North Carolina football team suggests otherwise. Players at UNC wear impact sensors in their helmets throughout the season. Results from these investigations suggests that even routine hits during practice can add up to cause concussions and, theoretically, set the stage for chronic traumatic encephalopathy. (On the first day of training camp one UNC lineman was recorded as having been hit in the head thirty-one times!)

Back in 1905, Gladwell reports, the question of whether football should be played in our nation's schools was raised to the level of the White House, when President Theodore Roosevelt called an emergency summit to discuss the issue. At the time, a professor at the University of Chicago called football a "boy-killing, man-mutilating, money-making, education-prostituting, gladiatorial sport". And in December of 1905, presidents of twelve prominent colleges met in New York and came within one vote of abolishing the sport at their institutions.

What does this mean for football in America? Nothing. Fans are willing to spend a lot of money to see men slam into each other's heads on the field. But, as a parent, you can do something. You can forbid your son from playing football.

Dr. C. Everett Koop turns 93 today

Happy birthday, Dr. Koop! C. Everett Koop, MD turns 93 years old today. Surgeon General of the United States under President Reagan from 1982 t0 1989, Koop (pictured circa 1974) was probably the most influential figure to have ever filled that office. I met with Dr. Koop during his open office hours on April 19, 1995 at Dartmouth Medical School's Koop Institute. I found Dr. Koop to be a really nice guy -- definitely more gentle than his stern appearance initially suggests. Since I was applying to medical school at that time, Koop and I talked a bit about our respective experiences with the admissions process. Koop told me that he had been rejected from Columbia Medical School, an institution that he had looked forward to attending since his childhood in Brooklyn. He described the rejection as a "major blow". But Koop got the last laugh. Decades later, he told me, at an event honoring his accomplishments, Koop was introduced to the dean of the Columbia Medical School and said, "See, if you had only accepted me, I would have made something of myself."

Is anyone assessing epidermal nerve fiber density in skin biopsies?

I recently received an advertising pamphlet from Therapath, a New York company offering to evaluate skin punch biopsy specimens in patients with suspected small fiber neuropathy. The pamphlet trumpets Therapath's proficiency, including "board certified neuropathologists meticulously reviewing cases". Although I have heard of this test, no clients of my practice have yet requested such a test. According to Therapath, the result is "reported as the average number of nerve fibers that cross the basement membrane at the dermal epidermal border, over a length of 1 mm. Making the correct diagnosis explains the symptoms, guides the evaluation for the underlying cause, and helps decide treatment". See the photomicrograph from Therapath's website of normal skin with small fibers (arrow) traversing the basement membrane (arrowhead) and coursing through the epidermis. Accompanying the pamphlet is a letter from "neuropathologist and laboratory director" William Harrington, MD in which he states that the American Academy of Neurology has added a practice guideline to include skin biopsy in the scope of practice when evaluating for polyneuropathies. He goes on to say that "skin biopsy for the determination of epidermal nerve fiber density is the most sensitive test for small fiber neuropathy". Therapath provides the clinician with a kit for biopsy collection and shipping to their facility at no extra charge. Eight to 12 days later, Therapath provides a full-color, quantitative laboratory report with images. If anyone has had experience with evaluating such biopsies, please comment on this post and provide us with your insights regarding the utility and technical requirements of this test. I'm not sure whether I would have to use a service such as Therapath's, or perform the service in-house. Thanks!

Pathology 2.0: The Time Has Come

You may not realize it, but by reading this blog post you are participating in "Pathology 2.0". What is Pathology 2.0? For that, read an edited transcript of remarks made by Dr. Keith J. Kaplan (pictured) at the College of American Pathologists Foundation June 12-14 "Futurescape of Pathology" conference in Rosemont, Illinois. Speaking of things 2.0, today is the opening day of the Health 2.0 conference in San Francisco. Subtitled "User-Generated Healthcare", the conference focuses on the ways in which Web 2.0 technology is being applied to healthcare today. Conference organizers define Health 2.0 on their website as follows: "Our definition is currently focusing on user-generated aspects of Web2.0 within health care but not directly interacting with the mainstream health care system. That means, a) search, b) communities, c) tools for individual and group consumer use. But clearly there are blurring boundaries between all these, and the question of connecting Health 2.0 user-generated content to the wider health care system—which hasn’t exactly adopted Web 1.0 with a flourish—is coming into closer focus as more clinicians and organizations start to use these technologies to communicate with consumers."

Online Biomedical Lectures for the Blue-Collar Neuropathologist

If you consider yourself a blue-collar neuropathologist, a nice resource has appeared on the web for you. Henry Stewart Talks, based in London, is providing free access to a wide variety of on-line biomedical lectures in the form of The Biomedical and Life Sciences Collection. One series of these talks focuses on neurodegenerative disease, which would be of particular interest to the practicing neuropathologist engaged in brain autopsy work. The talks are geared toward an audience looking for a more in-depth presentation than would be appropriate for a general pathologist or neurologist, but not so loaded with basic science as to be of no practical use. For now, Henry Stewart Talks is offering institutions, such as mine, free access to the talks on a trial basis. Alternatively, you can request a free trial as an individual by visiting the site. I recently watched a very nice lecture on the clinicopathologic aspects of frontotemporal dementia by Dr. John Hodges of Cambridge University (53 minutes) and a helpful talk by Dr. Peirluigi Gambetti of Case Western Reserve University on prion diseases (53 minutes). Hats off to Henry Stewart Talks for providing this resource!

A case of cerebral Baylisascariasis

A loyal reader sent in this wonderful photomicrograph from a recent case of cerebral Baylisascariasis (click on the picture to see it up close). A cause of eosinophilic meningoencephalitis, infection with Baylisascaris procyonis is typically characterized by necrosis and eosinophilic inflammation. Larvae are often encapsulated within fibrous tissue (reference 1). Although not particularly neurotropic, the larvae may reach the central nervous system and cause major tissue damage.

Baylisascaris procyonis is an intestinal roundworm endemic to the US raccoon population. Humans are infected by ingestion of worm eggs in raccoon feces. The median age for human infection is just over one year old, consistent with the propensity of young children to explore their environment orally (surprising that this behavior has not been naturally selected out of humans over the millenia!). I came across only one report of clinical recovery after infection (reference 2). Otherwise, cerebral Baylisascariasis results in either severe neurologic damage or death. That being said, subclinical infection has been suggested by a study in Chicago, which found 30 (8%) of 389 children 1–4 years of age were seropositive for B. procyonis, although none had experienced symptoms (reference 3).

The most common cause of eosinophilic meningitis in the United States is the presence of a ventriculoperitoneal shunt; but worldwide it is infection by Angiostrongylus cantonensis. In addition to Bayliscaris procyonis, other infectious causes of eosinophilic meningitis include Toxocara spp., Gnathostoma spinigerum, and neurocysticercosis (source: reference 2).

References:
1. Love S, et al, eds. Greenfield's Neuropathology, 8th edition. p. 1479.
2. Pai et al. Full recovery from Baylisascaris procyonis eosinophilic meningitis. Emerging Infectious Disease 13(6) p 928-30. June 2007
3. Brinkman WB, Kazacos KR, Gavin PJ, Binns HJ, Robichaud JD, O'Gorman M, et al. Seroprevalence of Baylisascaris procyonis (raccoon roundworm) in Chicago area children. In: Program and abstracts of the 2003 Annual Meeting of the Pediatric Academic Societies, Seattle, Washington; 2003 May 3–6. Abstract 1872. [cited 2007 Mar 29]. Available from http://www.abstracts2view.com/pasall/authorindex.php

Featured Neuropathologist: Craig Horbinski, MD, PhD

Today I profile Dr. Craig Horbinski (pictured), a rising star in the neuropathology firmament. If you follow the neuropathology literature, you are sure to hear about Craig in the coming decades as he sure to make a big impact on the field. After a short biographical sketch, Craig answers a few of my questions:

Craig Horbinski hails from snowy Buffalo, NY, where he did both his undergraduate training in Biology at Canisius College and a combined MD, PhD at the State University of New York at Buffalo. Craig’s work as a graduate student was on mechanisms of dendrite growth, requiring a lot of microscopy and morphometric analyses. After a 1-year postdoctoral research fellowship studying Parkinson Disease at the University of Pittsburgh, he did 3-year Anatomic Pathology residency at UPMC. During this time Craig developed an interest in oncogenesis, particularly as his residency training exposed him to cutting-edge molecular diagnostic approaches to neoplasms. Thus, when continuing his training as a fellow in neuropathology at Pitt, he focused his research on both the molecular diagnostics of gliomas and mechanisms underlying gliomagenesis, as well as the application of telemedicine to neuropathology. Upon completion of his neuropathology fellowship in July of 2009, Craig joined the faculty at the University of Kentucky in Lexington as an Assistant Professor in Neuropathology, where he is continuing his work on gliomagenesis and molecular diagnostics as an independent principal investigator. Craig is married to Christy and has a 1-year old son, Cedric. He and Christy are slated to adopt a baby from China, probably by early 2010.

1. Why did you decide to become a neuropathologist?

I’ve been attracted to the neurosciences since my sophomore year of college, which featured a fantastic course on neurobiology. Since I was already committed to being a physician, I thought neurology was the way to go (neurosurgery was out of the question). But as I went through medical school I discovered the field of pathology, in particular neuropathology. To me it seemed the best way to scratch both the research and clinical itches (so to speak), as neuropathology lends itself particularly well to those with combined-degree training.

2. Name a couple of important professional mentors. Why were they important to you?

The first person I have to acknowledge is Dennis Higgins, my thesis advisor back at SUNY Buffalo. He was a real gem, a pure scientist whose passion for science was both inspiring and infectious. It’s not an exaggeration to say I learned how to think like a scientist from him. Tragically he died of pancreatic cancer a few years ago; I think he would have been pleased to see how things have gone for me thus far. The second key person is Clayton Wiley, the Director of Neuropathology at the University of Pittsburgh. While I learned science from Dennis, I learned grantsmanship and administration from Clayton. He’s one of those exceedingly rare people who managed to succeed at all four pillars of an academic physician’s life: research, clinical, administration, and teaching. Plus he’s mastered the art of staying out of political brouhahas—not a trivial accomplishment in a big academic center. Even more intolerable is that he’s a terrific guy, very approachable, with a sharp, self-deprecating wit. Anyone who wants to know how to survive as a physician-scientist ought to emulate Clayton.

3. What advice would you give to a pathology resident interested in doing a neuropathology fellowship?

Be sure you are flexible with where you want to live. The job market for neuropathology is pretty good right now, but since brain tumors are relatively uncommon, only medium-to-large cities can typically sustain neuropathologists. That is, unless you are planning on doing full-time clinical, with some general surgical path mixed in. Another word of caution goes to those who want to develop an independent research program—most academic neuropath openings will claim they want you to do independently-funded research, but beware of red flags like being asked to commit 50% or more of your time to clinical work “until you get a grant” (which probably won’t happen if you’re devoting that much time to clinical), or splitting your clinical time between neuropath and general surgical path.

4. What city (other than Lexington, KY of course) would you like a future American Association of Neuropathologists meeting to be held and why?

I think Salt Lake City would be a neat change of pace from the typical destinations. It’s fairly easy to fly to, it’s relatively inexpensive, the weather’s good in June, and the mountain scenery is gorgeous.

When you've exhausted your differential diagnoses for a nerve mass, Dr. Kleinschmidt-DeMasters is here to help

In the same issue of Archives of Pathology and Laboratory Medicine that was referenced in the previous post, a team including Bette K. Kleinschmidt-DeMasters, MD (pictured) authored an interesting article entitled Rare Nerve Lesions of Non-Nerve Sheath Origin: a 17-year Retrospective Series. DeMasters, neuropathology chief at the University of Colorado in Denver, and her team did a computer search of all peripheral nerve masses at her institution from 1991 through mid-2008. After coming up with 458 cases, they threw out all the schwannomas, neurofibromas, and other nerve sheath tumors, ending up with a mere 37 cases to review. I was surprised by the number of spinal nerve root hemangioblastomas they came up with (7). Also notable were the four cases of brachial plexus "desmoid-type fibromatosis", which are not nerve masses per se, but are often at first mistaken for neurofibromas. The AFIP Tumor Atlas (Tumors of the Soft Tissues, third series) defines extra-abdominal desmoid fibromatosis as "an infiltrating fibroproliferative process that develops in the soft tissues deep to the subcutaneous tissue and is composed of fibrocytes, fibroblasts, and myofibroblasts set within a collagenous to myxoid stroma that possesses uniformly bland nuclear features" (page 71). Other unusual diagnoses are featured in this article include sclerosing meningioma invading nerve (WHO knows how to grade that one?), extrarenal rhabdoid tumor, and primary Ewing sarcoma of the brachial plexus. This article, along with a similar one published a few years ago by Kim et al. (see reference below), are good to keep in mind to help with your differential diagnosis the next time you are faced with a specimen called a "schwannoma" by the radiologist but bearing no histological resemblance to any of the typical nerve sheath tumors.

Reference: Kim DH, Murovic JA, Tiel RL, Moes G, Kline DG. A series of 146 peripheral non-neural sheath nerve tumors: 30-year experience at Louisiana State University Health Science Center. J Neurosurg. 2005;102:256-266.

Half of neuropathology fellowship positions go unfilled

An article entitled Fellowship Trends of Pathology Residents appears in the current issue of Archives of Pathology and Laboratory Medicine by Drs. Nikolaj Lagwinski and Jennifer L. Hunt. The following national data for 2006-2007 from the ACGME is provided in Table 5 of the article:

Number of Neuropathology Fellowship Programs: 35
Number of approved positions: 75
Number of positions filled: 39
Calculated fill rate (%): 52

In the News: Dr. Arie Perry Goes West

After many years at Washington University in St. Louis, Dr. Arie Perry (pictured below) has accepted a position at the University of California at San Francisco as Chief of Neuropathology. Dr. Perry is also editor-in-chief of Brain Pathology.

Best Post of June '09 - Ependymoblastoma: Dear, Damned, Distracting Diagnosis, Farewell!

The next in our series of "Best Posts of the Month" is from June 18, 2009.

In an article entitled "Ependymoblastoma: Dear, Damned, Distracting Diagnosis, Farewell!" published online in Brain Pathology, authors Alexander R. Judkins (UPenn) and David W. Ellison (St. Jude's, Memphis) adapt a line from Alexander Pope's poem A Farewell to London (1715) for their title. Judkins and Ellison conclude the following: "We believe that ependymoblastoma as a diagnosis is neither precise nor specific and that it is time once and for all to retire this diagnosis from the lexicon of neuropathology." For now, the World Health Organization tumor classification sytem continues to recognize ependymoblastoma as a distinct nosologic entity. These neoplasms are often large, supratentorial, and usually connect to the ventricles. Although there is no definitive feature of ependymoblastoma, the ependymoblastomatous rosette is a histologic characteristic that has been used in making the diagnosis. A photomicrograph of such a rosette from the Judkins & Ellison article is shown. In this picture, epithelial membrane antigen (EMA) immunohistochemistry highlights the limiting lumenal membrane of rossette. (Update: Although published online in December '08, I have yet to see this article published in the print version of Brain Pathology.)