Thursday, February 26, 2009

Why does the herpes virus love the temporal lobes?


After my recent lecture on infections of the CNS, Southern Illinois University medical student Mike Sinha came up to the podium to ask why the herpes virus had a predilection for attacking the temporal lobes. I passed Mike's question on to Dr. Tom Smith, the neuropathologist who provided the photographs (see above) of herpes encephalitis for Robbins and Cotran Pathologic Basis of Disease (7th edition). Dr. Smith wrote that the question is not completely resolved, but he directed me to a 2002 review article which addressed the issue (Journal of Neurology Neurosurgery and Psychiatry 2002;73:237-238). I quote from that article:

"Regarding the site specificity of herpes simplex encephalitis (HSE), the pathway of viral spread is probably more important than cell-type viral susceptibility. The unique anatomical localisation has been thought to result from entry of the virus via the olfactory pathway with spread along the base of the brain to the temporal lobes, a view that is supported by the immunocytochemical evidence of HSV antigens in the olfactory tract and cortex, as well as temporal lobes, hippocampus, amygdaloid nucleus, insula, and cingulate gyrus in patients dying from HSE. Another suggestion is that HSE may result from viral spread from the trigeminal ganglia to the temporal and frontal cortex, a view that is consistent with this known site of HSV latency."

Thanks to Mike Sinha for a provocative question and to Tom Smith for researching the response.

Tuesday, February 24, 2009

Father convicted in infant son's death

Because it has involved opposing neuropathologists (including Dr. Mark Cohen, pictured during his testimony for the defense), Neuropathology Blog has been following the Colorado court case involving the death of 11-week-old Jason Midyette. Jason's 29-year-old father, Alex, was convicted last week of abusing his son. Dr. Cohen claimed that the multiple broken bones suffered by the infant were related to a condition known as methylenetetrahydrofolate reductase deficiency, an autosomal recessive disorder of folate metabolism. Despite defense testimony by both Cohen and forensic pathologist Dr. Jonathan Arden, the jury could not be convinced that Alex had nothing to do with his son's death. The neuropathologist hired by the prosecution was Dr. Robert Ross Reichard of the University of New Mexico. Legal experts say that it is unlikely that Alex will serve more than 16 years for his crime mainly because Alex's wife, Molly, is already serving 16 years in prison for knowing and reckless child abuse resulting in death. Sentencing for Alex Midyette will take place on April 20th.

Thursday, February 19, 2009

Best Post of November '08: Whither the Illusory Cowdry B Inclusion of Polio

And now for another installment of the "Best of the Month" series. In this post from November 13, 2008, I wrote about the alleged existence of polio-related Cowdry B inclusions. No one has yet been able to produce a photomicrograph of such an inclusion, despite having increased the reward from $10 all the way up to $12. Anyway, here's the post:


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In a recent post about poliomyelitis, the illustrious Dr. John Donahue of Brown University (pictured) correctly pointed out that I did not mention the presence of Cowdry B inclusions in my histological description of the disease. Having never seen polio under the microscope, I went looking in textbooks and on the web for a photomicrograph of a polio-related Cowdry B inclusion. Failing in my search, I turned to the esteemed Dr. Tom Smith of the University of Massachusetts to see if he had such a picture. With his permission, I quote Dr. Smith’s email to me:
“I have the same problem you and everyone else seems to have -- I've never seen one myself and cannot find any photos of one either in my own file or anywhere in books or on the web. I remember reading a description a long time ago - I think it might have been from the old AFIP neuropath teaching slide set - that they were supposed to be small eosinophilic (?) nuclear inclusions that were sometimes seen in neurons in poliomyelitis. I don't remember actually seeing them in the slide in that teaching set. From the description, I had the impression they might have resembled Marinesco bodies or maybe even normal but prominent nucleoli... or perhaps those small inclusions seen in some neurodegenerative dementias. They don't seem to be as 'specific' as Cowdry A inclusions and perhaps they don't even exist? Frankly I think Cowdry B inclusions have reached the point where they should be relegated to the trashbin of neuropathology.” (Emphasis added.)
I recently photographed a Marinesco body (see picture, arrow points to the eosinophilic body) within the
nucleus (outlined) of a pigmented neuron in the substantia nigra.
Could the Cowdry B inclusion be an elaborate hoax perpetrated upon us by Dr. E.V. Cowdry when he first described Cowdry type A and type B inclusions in 1934? Dr. Smith’s response:
“Well, I doubt that it was a hoax but I think some of those folks were quite prone to seeing things that just the passage of time (and new information) has proved to be ‘not real’. Another case in point - how many Alzheimer type 1 astrocytes have you seen?”

I then wrote back to the individual who got me started on this hunt for the illusory Cowdry B in the first place: John E Donahue, MD. Here’s what Dr. Donahue had to say about the issue:
“I think these descriptions are very old and go back to the day where everything was described visually, without knowing etiology. (Remember, there are eight structures of Scherer from the original 1938 article, only three of which are really relevant anymore, and maybe even the gliosarcoma being a tertiary structure may be going the way of the dinosaur since I've heard recently that the gliosarcoma arises from a single precursor cell)…”
Fuller and Goodman, in Practical Review of Neuropathology (Lippincott, 2001), define a Cowdry B purely on morphological grounds -- with no implication as to the cause (polio or otherwise) -- as being small, eosinophilic, intranuclear inclusions with no halo and causing no nuclear effacement. I quote page 20: “[T]he quotidian Marinesco bodies that are routinely observed in the neurons of the pigmented brainstem nuclei are sterling examples of the Cowdry type B beau ideal.”

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Perhaps the Marinesco body, rather than a “sterling example”, may in fact be the only example of a Cowdry B inclusion! Come to think of it, I think I’ll offer a $10 reward for anyone who can send me a photomicrograph of a polio-related Cowdry B inclusion. Email me the photo at brian.moore@ucdenver.edu

 I hope you have better luck finding one than I did!

Tuesday, February 17, 2009

Medpedia.com launched today


Medpedia was launched today to answer the concerns expressed by many that medical professionals and patients have become too dependent on Wikipedia for quick answers about medical topics. Medpedia has plenty of authoritative weight behind it: Harvard, Stanford, UC Berkeley, and U Michigan are chief backers of the project.

According to a press release issued today by Ooga Labs, the San Francisco-based technology greenhouse which is funding and managing the project, the "release of the Medpedia Platform includes three interrelated services: a collaborative knowledge base, a Professional Network and Directory for health professionals and organizations, and Communities of Interest in which medical professionals and non-professionals can share information about conditions, treatments, lifestyle choices, etc."

Speaking of the Medpedia platform Nancy Brown, CEO of The American Heart Association said: “This platform provides new opportunities for our physician audience to network and share knowledge with other medical professionals around the world who are not a part of the American Heart Association. And, Medpedia’s medical encyclopedia provides the public with convenient access to credible health information, with varying perspectives and resources included.”

I am one of the volunteer editors of the project and have already contributed some photomicrographs and referenced information to the Medpedia medical encyclopedia. I hope the project does well. Please give it your support!

Saturday, February 14, 2009

Best Post of Oct '08 - Polio: once ubiquitous, now a disease of poverty

Next in my "Best Post of the Month" series is the entry for October of 2008. I wrote this post on October 15th as part of Blog Action Day, a yearly event which gets bloggers worldwide to focus on one particular issue to raise global awareness of the topic. In 2008, the topic was poverty. Here's the post:

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.


This post is part of Blog Action Day 08 - Poverty

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/

Monday, February 9, 2009

Neuropathologist provides alternate explanation for child death in Colorado abuse case


Last week I posted that neuropathologist Mark Cohen testified for the defense in a high-profile child death case where a father is accused of causing the death of his son. The boy's mother is already serving time for her role in the child's death. Cohen, on faculty at Case Western in Cleveland, testified for the defense in the state of Colorado's case against Alex Midyette, whose son was found to have multiple broken bones at the time of his death. The local news channel reports that Mr. Midyette (pictured entering the courtroom with his lawyers) declined to testify in his trial today. Dr. Cohen stated that the 11-week-old infant suffered from methylenetetrahydrofolate reductase deficiency, an autosomal recessive disorder of folate metabolism causing elevated plasma homocysteine levels. Patients with this rare disease suffer from neurologic developmental delay, and exhibit abnormalities of CNS myelination. In the article I read on the topic (see reference), no mention is made of skeletal abnormalities. So, I am not sure how one would explain the multiple broken bones in this case by invoking this metabolic disease. In any case, we await the verdict.

Reference: Bishop L, Kanoff R, Charnas L, et al. Severe methylenetetrahydrofolate reductase (MTHFR) deficiency: A case report of nonclassical homocysteinuria.
Journal of Child Neurology. Volume 23, Number 7. July 2008, p 823-828.

Friday, February 6, 2009

Neuropathologist is "star witness" in high-profile child death case


Dr. Mark Cohen (pictured), a well-known neuropathologist and friend who is frequently featured on this blog, made the news recently as a defense witness in a high-profile child abuse case going on in Colorado. This link will bring you to a report on the case by the local CBS television affiliate. The report states that "[t]he defense called its star witness to the stand Wednesday morning. Mark Cohen, a high profile neuropathologist, says Jason died from a rare condition called 'metabolic disease,' and not from child abuse." You can see a video of Dr. Cohen's testimony on the site as well.

Wednesday, February 4, 2009

Best Post of Sept '08: Extramedullary hematopoesis is not an uncommon finding in subdural hematomas

The next in my "Best of the Month" series, in which I feature my favorite post from each month, is from September 26, 2008:

I received a case in consultation this week from a general pathologist who was concerned about clusters of unusual-looking cells within a chronic subdural hematoma (SDH), a specimen the surgeons call a "subdural membrane" (look at the picture above of a resected chronic subdural hematoma from Greenfield's textbook to see why surgeons use that term). I felt that the cluster of cells represented foci of extramedullary hematopoesis (EMH). Another general pathology colleague was doubtful that such a phenomenon was likely in an patient with no other hematological disorders. I countered that perhaps 25% of SDH cases in hematologically intact patients show EMH. This prompted an email to the illustrious Hopkins neuropathologist Peter Burger (pictured), who provided me with a reference to an 2007 article by Juan Rosai and colleagues. In their article, Rosai and friends cited a larger study by Muller et al. (reference 1) in which "a microscopic study of 130 chronic subdural hematomas... found nucleated red blood cells in 41 cases (32%). In a subsequent study, the same authors found erythroblasts in 33% of 38 cases, and this percentage increased to 57% after serial sections were taken." The Rosai article itself (reference 2) describes in detail two cases with the aim of documenting the fact that "such lesions can fool the 'general' surgical pathologists, including some who can hardly be regarded as 'junior'."
References:
1. Muller W, Zimmermann E, Firsching R. Erythropoiesis in chronic subdural hacmatomas. Acta Neurochir (Wien). 1988;93:137-139.
2. Kuhn E, Dorji T, Rodriguez J, Rosai J. Extramedullary Erythropoiesis in Chronic Subdural Hematoma Simulating Metastatic Small Round Cell Tumor. International Journal of Surgical Pathology 15:3 [July 2007] p.288-291.