Friday, October 31, 2008

Happy First Birthday to Neuropathology Blog!

Today marks the first anniversary of Neuropathology Blog! There have been 128 posts in the last year, and over 200 comments by readers. Geographic tracking shows that people from as near as Springfield, IL and as far away as India and Japan have accessed this blog. Also, there have been more than 1,200 views of my profile during the past 12 months. I've enjoyed the experience, and hope that I've provided some education and entertainment along the way. I look forward to the next year of neuropathology blogging!

Tuesday, October 28, 2008

14-3-3 protein: What is it good for?

The neurology residents and I got into a discussion today about the utility of the 14-3-3 protein immunoassay on CSF fluid. I published a post on this assay many months ago in which I called it essentially useless. Now that I've done some more research on the topic, I've revised my opinion and feel that it is a decent confirmatory test -- but only in those cases in which there is a fairly high pre-test likelihood of prion disease based on observation of an evolving mental deterioration along with some type of involuntary movement or periodic EEG activity. In a prospective study of 110 patients done in The Netherlands (see reference below), it was found that the 14-3-3 assay was 97% sensitive and 87% specific. It must be emphasized that these results are based on a population of patients who have other clinical features that point to a prion disease. Of course, routine CSF tests should also be run on these patients because, as the authors state, "abnormalities of the routine examination of CSF almost exclude CJD as a diagnosis". They go on to say that "conditions associated with increased cell counts or total protein (e.g., meningitis and encephalitis) are known sources of false-positive 14-3-3 test-results. Therefore, it is reasonable to consider other diagnoses first if total protein or cell count is increased in patients with initially suspected CJD."
(Reference: Lemstra AW, et al. 14-3-3 testing in diagnosing Creutzfeldt-Jakob disease: A prospective study in 112 patients. Neurology 2000;55:514-516.)

Thursday, October 23, 2008

3D imaging and virtual reality technology is the next wave in brain tumor diagnosis and treatment


A friend emailed me a link to the Iowa State Virtual Reality Applications Center, where they are doing interesting things with 3D rendering that will have implications for brain tumor operations. Here's what one researcher there, Eliot Winer (pictured), is up to:
"Dr. Winer's research team is currently working on a project that will allow physicians to view 3-D images of patients' complex internal systems. The images could be delivered over the internet or could be rendered in real-time while the patient undergoes surgery, thus providing more complete and timely information. Essentially, Dr. Winer believes that complex systems will eventually become data centric, a term he coined to describe a system that addresses multiple fidelities. In short, 'all the data has to come together so everyone can access the data simultaneously and collaborate more effectively.'"
I don't profess to know exactly what all this means, but it sounds like a an exciting frontier in cancer treatment. Let's hope pathologists, as they move to toward a transformation of their profession, are involved in the development and implementation of this new technology.

Tuesday, October 21, 2008

College of American Pathologists Set to Transform the Profession


The College of American Pathologists (CAP) announced a new initiative at the September national meeting in San Diego entitled: The CAP Campaign for the Transformation of the Specialty of Pathology. A cornerstone of the campaign is the CAP's new certificate program to be launched in June '09 through the CAP Institute . The certificate program is designed to allow pathologists to earn time-limited certificates in broad areas of expertise not currently offered as a subspecialty board certification (such as breast pathology) as well as in narrow skill sets (such as ultrasound-guided fine needle aspiration). Read more about all the efforts encompassed by the campaign here. Thanks to CAP House Delegate Doug Shevlin, MD (pictured on the right next to me on the left) who informed me about this exciting new initiative by the CAP.

Friday, October 17, 2008

Brain Food

A reader from Springfield, IL recently sent me this picture of a market that once stood on Chouteau Avenue in St. Louis.  "Brains & Eggs" was once a popular dish, particularly in the southeastern United States. 

Wednesday, October 15, 2008

Polio: Once ubiquitous, now a disease of poverty

Today is Global Blog Action Day ‘08, which this year focuses on the topic of poverty. One important place where poverty and neuropathology intersect is in the disease known as poliomyelitis (polio). This is a highly infectious viral disease, which mainly affects young children. The virus is transmitted through contaminated food and water, facilitated by crowding and poor sanitation. The virus multiplies in the intestine and then can invade the nervous system. In a small proportion of cases, the disease causes paralysis, which is often permanent. Although the spinal cord is usually involved, the distribution of paralysis depends upon the distribution of lesions within the CNS. The paralysis is usually asymmetric and involves the legs more often than the arms.

There is no cure for polio, it can only be prevented through immunization. The introduction in the 1950s of the Salk vaccine and in the early 1960s of the Sabin vaccine caused a sharp decline in the incidence of poliomyelitis. Polio vaccine, given multiple times, almost always protects a child for life.

Histopathologically, neuronophagia is prominent from a very early stage, as lymphocytes and microglia aggregate around dying neurons like vultures around a carcass. (The photomicrograph depicts neuronophagia of a neuron in the inferior olive of a patient with brainstem encephalitis caused by coxsackievirus.) Eventually, only clusters of microglia remain where the neuron once lay. In patients who die years after onset of the illness, autopsy examination of the spinal cord reveals anterior horn neuronal loss and corresponding discoloration of anterior nerve roots.

The World Health Organization (WHO), in collaboration with other agencies, has been working on a global immunization initiative since 1988. The Global Polio Eradication Initiative has been working to immunize children in impoverished regions of the world, where education and health care resources are scarce. The results of this initiative are encouraging: polio cases have decreased by over 99% since 1988 -- from an estimated 350, 000 cases then, to 1,997 reported cases in 2006. In 2008, only four countries in the world remain polio-endemic, down from more than 125 in 1988. The remaining endemic countries are Afghanistan, India, Nigeria and Pakistan.

References:

1. World Health Organization website: http://www.who.int/topics/poliomyelitis/en/

2. Greenfield’s Neuropathology (8th edition), Love S, Louis DN, and Ellison DW (eds). Edward Arnold Publishers (2008). Chapter 17: Viral Infections. Love S and Wiley CA. pages 1285-1291.

3. Global Polio Eradication Initiative website: http://www.polioeradication.org/


Saturday, October 11, 2008

The best meningioma lecture I've ever seen

Dr. Mark Cohen (pictured) of Case Western Reserve University just published a podcast presentation on frontalcortex.com that is by far the very best lecture on meningiomas and their mimics that I have ever seen. He incorporates the latest World Health Organization criteria on grading of meningiomas in a truly masterful presentation. Plus, Cohen has a great speaking voice. Pathologists, neurologists, neurosurgeons: go see this lecture!

Thursday, October 9, 2008

Ophthalmic pathology faces a shortfall

A front page feature in the September ’08 issue of CAP Today, from the College of American Pathologists, alerts us to the fact that ophthalmic pathology is in a decline more precipitous than the Dow Jones Average of late. Quoted in the article is Dr. Thaddeus Dryja, with whom I did an eye pathology rotation during my fellowship training. Dr. Dryja says: “Whenver you read about a shortage of any type of professional …. what’s really meant is that employers don’t want to pay what the work is worth. If you paid enough, you’d have enough nurses and high-tech engineers, for example. Eye pathology is no different. Primary care physicians are also on the list.” The article lists that among the conditions that can be missed by pathologists not specifically trained in ophthalmic pathology are: keratectasia, primary intraocular lymphoma, sebaceous carcinoma of the eye, and acanthamoeba infection causing keratitis. To address the problem, some institutions are turning to cyber solutions to expose residents to an adequate volume of material. Among the institutions providing web-based tools (some with a fee) are the University of Illinois at Chicago, Emory University, and Duke University. Duke hosts The EyePathologist, which is free and includes a database of more than 5,000 vision-related diseases and 4,000 images. There’s also a glossary of more than 6,000 ophthalmic terms. The site, authored by neuropathologist Gordon K. Klintworth, MD, PhD. (pictured above), has gained a lot of popularity, with more than 9,000 current registrants from 158 countries.

Monday, October 6, 2008

"... this is a bad cell because I sat next to somebody who told me it was a bad cell..."

After a clinician presents a case at a clinicopathologic conference, he or she will not infrequently turn to the pathologists and say: "and now for the answer". The truth is that surgical pathology is interpretive and subjective. I was reminded of this when I read a quotation from Richard Friedberg, MD, PhD (pictured), chair of pathology at Baystate Health in Massachusetts, in the latest issue of CAP Today from the College of American Pathologists. Dr. Friedberg was discussing the introduction of computer-assisted imaging analysis into his practice with the aim of improving inter-observer reproducibility in the interpretation of surgical immunohistochemical slides. Here's what Dr. Friedberg had to say on the topic: "We're getting away from the idea that this is a bad cell because I sat next to somebody who told me it was a bad cell -- that sort of guild mentality with anointed experts -- and moving toward more quantifiable, reproducible, validated, specific, and reliable approaches." Finally, anatomic pathology is taking its first, furtive steps into the 21st century!

Thursday, October 2, 2008

CNS Whipple's disease factsheet

The topic of CNS Whipple’s disease came up in a recent email exchange, so I thought I’d share with you a fact sheet on the disease:

DESCRIPTION:

First described by George Whipple in 1907, Whipple disease is a multisystem disorder that usually includes the intestinal tract. The causative organism is a Gram-positive actinomycete called Tropheryma whippleii.

EPIDEMIOLOGY:

Interestingly, Whipple’s disease occurs about six times more commonly in men than in women. The disease tends to occur in late middle age.

CLINICAL PRESENTATION:

Most patients present with such symptoms as arthralgia, weight loss, steatorrhea, lymphadenopathy, and hyperpigmentation. Some patients develop neurological disease, usually in combination with systemic symptoms. The most common neurologic manifestations are dementia, ophthalmoplegia, hypothalamopituitary dysfunction, and myoclonus. Occulofacial-skeletal myorhythmia is particularly suggestive of Whipple’s disease. Only rarely is Whipple’s disease confined exclusively to the central nervous system.

PATHOLOGIC DIAGNOSIS:

Intestinal biopsy: The diagnosis is usually made by jejunal biopsy, which demonstrates the characteristic macrophages containing PAS-positive rod-shaped structures, termed sickle particle containing (SPC) cells. This microscopic finding may be present even in patients without clinically apparent intestinal involvement. PCR-based assays of intestinal tissue may allow the confirmation of suspected CNS Whipple’s disease, even when histology is not revealing. In patients with neurological manifestations, SPC cells may rarely be found in the CSF.

Brain biopsy: Exceptionally, brain biopsy is required to establish the diagnosis; however, PCR analysis of CSF or synovial fluid allows the diagnosis to be made in most instances. Microscopically, accumulation of macrophages is seen, often with a perivascular distribution, surrounded by a lymphocytic and plasma cell inflammatory reaction of variable intensity, and gliotic brain tissue containing hypertrophied astrocytes. Macrophages with lipid-filled cytoplasm containing sickle-shaped inclusions that are PAS-positive are seen [see figure]. The organisms, which are also Gram-positive and methenamine silver-positive, can also be seen free within the tissue.

DISEASE DISTRIBUTION WITHIN THE CNS

The pathology is usually characterized by small lesions disseminated throughout the entire CNS but especially abundant in the cortex. Larger intracerebral pseudo-tumors are uncommon. Leptomeningeal involvement is occasionally complicated by tiny infarcts scattered throughout the brain; and first presentation as a multiple stroke syndrome has been reported.

REFERENCE:

Greenfield’s Neuropathology (8th edition), Love S, Louis DN, and Ellison DW (eds). Edward Arnold Publishers (2008). Chapter 18: Bacterial Infections, by Brown E. and Gray F. pages 1426-7.

Wednesday, October 1, 2008

Neuropathology Blog adds a new feature

I’ve added a new gadget which allows you to become part of the public fan base for this blog. Followers allows you to see who else is following this blog, see the blogs they’re writing, and read the other blogs they’re following. It’s a means of organically creating a network of people interested in neuropathology. Readers who become official followers of the blog can have their profile picture displayed in the followers list if they so wish. Finally, this feature allows you to see the blogs I follow by clicking on view my complete profile under my picture in the column on the right. Just click the “follow this blog” link on the right side of this page, and add yourself as a regular reader. Let’s see where this brings us!