Best Post of August 2011: Benignity in meningioma indicated by smiley face nucleus

The next in our "Best of Month" series is from August 16, 2011:

Drs. John Donahue and Ed Stopa sent in the photomicrograph below from an article they published in 1999 describing a benign meningioma. They conclude: "In this case, another factor in favor of the tumor being benign is that its nuclei are smiling (arrow)."

New Neurology Neuromuscular Medicine Fellowship Established by University of Connecticut

The University of Connecticut School of Medicine/Hospital for Special Care Neuromuscular Fellowship is offering an ACGME accredited one-year program emphasizing clinical bedside and clinical research experience. The primary site is based at University of Connecticut Health Center, John Dempsey Hospital in Farmington, Connecticut. The other major participating site is Hospital for Special Care, New Britain, CT, and Connecticut Children's Medical Center in Farmington, CT. The fellow will be exposed to a full range of emergency, inpatient and outpatient management of neuromuscular disorders. Neuromuscular teaching will take place through didactic sessions scheduled throughout the year, inpatient consultations, adult and pediatric EMG and neuromuscular clinics. Contact Agnes Jani-Ascadi, MD at jani-acsadi@uchc.edu for more information.

Landreth scores a hit against Alzheimer's with bexarotene

Tomorrow’s edition of the journal Science will report on how Professor Gary Landreth, about whom I recently posted, and his team discovered that the cancer drug bexarotene can quickly reverse Alzheimer’s symptoms in animal models. Within 72 hours of administration, the medication  halved the number of plaque deposits closely associated with this degenerative brain disease.  Additionally, the signs of cognitive and memory deficits disappeared within that same brief time period.

For more details, watch this two-minute video from Case Western: http://www.youtube.com/user/case#p/a/u/0/HdYdYeNAYpU.

Time to revise your Alzheimer brain autopsy template

Time to put the NIA-Reagan criteria for the neuropathologic diagnosis of Alzheimer's behind you and revise your autopsy reports to reflect the consortium report by the National Institute on Aging and Alzheimer's Association (the NIA-AA criteria). Neuropathologist Tom Montine, MD, PhD headed up the effort to revise the 1997 criteria. According to Medscape News, Montine said there were three main points to be made regarding the new criteria:

Dr. Thomas Montine

'"The first is that it's no longer necessary that someone carry a clinical diagnosis of dementia in order to make a pathological diagnosis of [AD]. We have separated those 2 entities because we now understand that there is a preclinical stage of the disease. That's the major philosophical point... The second point is more on the technical side," he said. The guidelines recommend the "ABC" staging protocol for the neuropathologic changes of AD, based on 3 morphologic characteristics of the disease: A is for amyloid, B is for Braak neurofibrillary tangle staging protocol, and C is for the Consortium to Establish a Registry for AD neuritic plaque scoring system. For all cases, regardless of clinical history, the guidelines state that reporting should follow the format of these examples: 'Alzheimer Disease Neuropathologic Changes: A1, B0, C0' or 'Alzheimer Disease Neuropathologic Changes: A3, B3, C3.' The ABC score is then transformed into 1 of 4 levels of AD neuropathologic change: not, low, intermediate, or high." The third point deals with comorbidity. Although AD is the most common cause of dementia and can exist in a "pure" form, it commonly coexists with pathologic changes of other diseases that can also contribute to cognitive impairment, the document notes. The most common comorbidities are Lewy body disease, vascular brain injury, and hippocampal sclerosis, as well as other neuropathologic changes such as argyrophilic grain disease and TDP-43 inclusions. The new recommendations more explicitly define the manner in which these comorbidities are to be evaluated.

Here's the reference you can put at the end of your new reports:
Hyman BT, Phelps CH, Beach TG, et al. National Institute on Aging - Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease. Alzheimer's & Dementia: The Journal of the Alzheimer's Association. Volume 8: Issue 1. Pages 1-13, January 2012.

Case Western's Gary Landreth explores bexarotene as a pontential Alzheimer therapeutic

Gary Landreth, PhD

Dr. Mark Cohen tells me that a guy worth watching on the Alzheimer research front it Dr. Gary Landreth from Case Western Reserve University. And, as anyone who reads this blog regularly knows, when Mark Cohen talks, I listen. According to the Alzheimer Research Forum (from which I am blatantly plagarizing in the remainder of this post),  Landreth works on ApoE-directed therapeutics. As one of the genes involved in cholesterol homeostasis, ApoE is regulated transcriptionally by receptors which form heterodimers with the retinoid X receptor (RXR). Working with APP transgenic mice, Landreth found that an RXR agonist, bexarotene, induces brain ApoE quickly and robustly. This induction precedes a rapid decline in brain amyloid, an increase in plaque-clearing microglia, and improvements in cognitive performance. Landreth noted that bexarotene is an FDA-approved chemotherapeutic that readily crosses the blood-brain barrier and has minimal side effects, most of which are associated with its action on lipid homeostasis. Hence, this drug minimally represents a test of the role of Aβ in AD and, maximally, may represent an AD therapeutic. These finding raise the question of the utility of the drug in ApoE4-positive individuals. You go, Gary!

How we're doin'

I just checked the stats on Neuropathology Blog just to see where we stand. Here's where we stand at the moment:

So far today:
Number of pageviews: 291

Entire history since blog's inception in October of 2011:
Blog posts: 364
Comments: 746
Pageviews total: 189,440


Not too bad!

Best Post of July 2011: Formal Guidelines for Alzheimer's Genetic Testing Issued

The next in our "Best of the Month" series is from July 19, 2011:

Dr. Edward B. Lee

In recent posts, I discussed the availability of direct-to-consumer ApoE testing and the fact that I myself submitted buccal cells to 23andMe.com to discover my own ApoE status. The illustrious Eddie Lee, MD, PhD just emailed me news that the American College of Medical Genetics and the National Society of Genetic Counselors have recently issued formal guidelines regarding ApoE testing in patients. Reported and discussed on the Alzheimer Research Forum, the guidelines, published in the June issue of Genetics in Medicine, identify which individuals may benefit from genetic testing.

The Area Postrema is not the only place where the BBB is lacking

I'll paraphrase a question posed by one of my 2nd-year students at Southern Illinois University School of Medicine:

I understand that the Area Postrema was a site where there was increased penetrability of the blood brain barrier. I am not sure, but thought I had come across additional sites of increased penetrability last year in my reading. Are there other sites where there is increased permeability of the BBB?

In pondering an answer to this question, I immediately thought of the illustrious Dr. John Donahue, consummate neurologist, neuropathologist, and neuroanatomist.  I posed the question to him and got the following response:

Dr. John Donahue, Brown University, Providence, RI

"Not increased permability of the BBB.  NO BBB!  Area postrema is one of the circumventricular organs, areas in the brain that lack a BBB.  Being the vomiting center, it is imperative that it lacks a BBB so that it can sample the systemic circulation.  Being in the medulla, it is the only circumventricular organ that is adjacent to the fourth ventricle; all of the others are adjacent to the third.  It is the only paired circumventricular organ; all of the others are single and midline.  The other circumventricular organs are subfornical organ, organum vasculosum of the lamina terminalis, median eminence, posterior pituitary gland, subcommissural organ, and pineal gland."

There you have it!

Frosted Cerebellum

In frigid Massachusetts, forensic neuropathologist Peter Cummings, MD awoke this morning to find a cerebellum frosted on his bedroom window. Atrophic, yes, but a cerebellum nonetheless.

Naegleria-tainted neti pots possibly killed two people

Naegleria fowleria (photo courtesy of Dr. Mark Cohen)

Now that it's winter and our noses and sinuses are being dried out by our heating systems, many of us turn to neti pots (also known as 'nose bidets'). The illustrious J. Clay Goodman, MD, neuropathologist at Baylor, just sent me an article from The Houston Chronicle warning people to use distilled, bottled, or boiled water. Officials in Louisiana are investigating whether a 51-year-old woman and a 20-year-old man both contracted the brain-eating amoeba Naegleria fowleri after using tap water in their neti pots. The disease, while rare, is most commonly contracted after inhaling water from a lake, pond or river. If investigators confirm the two victims died after using tap water from a neti pot it will be the first time the disease has been contracted from tap water.

Brigham and Women's Hospital Names Neuropathologist as New Chairman

Dr. Jeffrey A. Golden

In an obvious attempt to keep up with Massachusetts General Hospital, whose pathology chief is neuropathologist Dr. David Louis, Brigham and Women's Hospital in Boston has just announced that another neuropathologist, Dr. Jeffrey Golden, will become chair of pathology at that institution. Effective March 1, 2012, Dr. Golden will become the Ramzi S. Cotran Professor of Pathology at Harvard Medical School.  Brigham President Betsy Nabel, MD had this to say in a statement released today: Dr. Golden comes to BWH "from The Children's Hospital of Philadelphia, where since 2008, he has been serving as Pathologist-in-Chief in CHOP's Department of Pathology and Laboratory Medicine, cited as one of the leading pathology and developmental biology programs in the U.S. and one of the top NIH-funded research programs in Pathology.... Dr. Golden is recognized as an outstanding clinician, a highly skilled educator focused on training the next generation of physician/scientists in pathology and developmental biology, and a cutting-edge basic and translational research leader.  His studies in the multiple aspects of developmental biology and early nervous system development are key to gaining a greater insight into the pathogenesis of human diseases, including brain malformations, mental retardation, epilepsy and autism.  His efforts to date of establishing and elevating the bench to bedside and back to bench paradigm in the fast changing field of developmental biology and molecular diagnostics reflects a true commitment to quality and excellence in the application of new knowledge at the front lines of patient care."

As one neuropathologist commented to another: "Apparently neuropath is now ruling the world."