neuropathology blog

Landreth scores a hit against Alzheimer's with bexarotene

2012-02-09T17:44:00.001-06:00

Tomorrow’sedition of the journal Science will report on how Professor GaryLandreth, about whom I recently posted, and his team discovered that the cancer drug bexarotene can quickly reverseAlzheimer’s symptoms in animal models. Within 72 hours of administration, themedication halved the number of plaque deposits closely associated with thisdegenerative brain disease. Additionally, the signs of cognitive andmemory deficits disappeared within that same brief time period.

Formore 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

2012-02-06T13:23:00.001-06:00

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.'

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

2012-02-05T08:15:00.001-06:00

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'

2012-01-19T14:48:00.001-06:00

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

2012-01-13T19:44:00.000-06:00

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

2012-01-09T16:07:00.000-06:00

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 Postremawas 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 increasedpenetrability last year in my reading. Are there other sites where there isincreased 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 theBBB. NO BBB! Area postrema is one of the circumventricular organs,areas in the brain that lack a BBB. Being the vomiting center, it isimperative 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 fourthventricle; all of the others are adjacent to the third. It is the onlypaired 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 pinealgland."

There you have it!

Frosted Cerebellum

2012-01-04T10:31:00.002-06:00

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

2011-12-16T14:59:00.000-06:00

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

2011-12-14T16:28:00.000-06:00

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 isrecognized as an outstanding clinician, a highly skilled educator focused on training the next generation of physician/scientists in pathologyand developmental biology, and a cutting-edge basic and translational research leader. His studies in the multiple aspects of developmental biology andearly 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."

Improvements Recently Made to the AANP Website

2011-12-12T15:52:00.000-06:00

The website for the American Association of Neuropathologists has recently undergone some improvements that might be of interest to NeuropathologyBlog readers:

- The membership directory should be changed so itis searchable by location (hospital, city, or state), as well as by name.

- The Education Section provides useful links for those of us (myself included) who need to get our SAM credits in to the American Board of Pathology for maintenance of certification.

- A new tab has been added under the ProfessionalAffairs heading, entitled “Survey". Results of recent AANP surveys are posted here.

- A new heading for the left hand column onthe home page has been added entitled “Links of interest". Several links pertinent to neuropathologists are listed. (Hey, where's NeuropathologyBlog?!?)

Thanks to AANP Vice-President Elect Liz Cochran, MD for providing me with this information.

Best Post of June 2011: A 58-year-old woman with headache and unsteadiness of gait

2011-12-04T21:53:00.001-06:00

The next in our "Best of the Month" series is from June 14, 2011:

Here's a recent case of mine involving a lesion in the third ventricle of a 58-year-old woman who presented with headache and unsteadiness of gait. First, the imaging:


Axial CT

Sagittal T1 MRI

Axial T2 MRI

Coronal Gradient Echo

The neuroradiologist thought perhaps the lesion was a craniopharyngioma. But, the neurosurgeon was surprised that the lesion seemed to "pop out". Here's the specimen I received:

Outer Surface

Cut Surface

I smeared some of the viscous fluid from the cut surface onto a glass slide, cover-slipped it, and viewed it under polarized light:

Those cholesterol crystals certainly seem to suggest the possibility of craniopharyngioma. But, craniopharyngiomas do not have a smooth outer surface and do not just "pop out" into the neurosurgeon's hand. Here was my first glimpse of the histology the next day:

Cholesterol clefts and giant cells. Note in the upper picture that this xanthogranulomatous reaction appears to be continuous with the choroid plexus. Could this be a xanthogranuloma of the choroid plexus? I considered that, until I looked elsewhere on the slide and saw this:

This is the ciliated epithelium characteristic of a colloid cyst of the third ventricle, a tumor that can indeed "pop out" into the neurosurgeon's hand. Gross inspection did not reveal a cyst per se because the exuberant xanthogranulomatous reaction obliterated it. Cases like this have been described in the literature. For example, Dr. David Louis and colleagues wrote in a 1994 article entitled Third ventricle xanthogranulomas clinically and radiologically mimicking colloid cysts: Report of two cases (Journal of Neurosurgery. 81(4):605-9, 1994 Oct.) that "histopathologic examination revealed xanthogranulomas of the choroid plexus with only microscopic foci of colloid cyst-like structures." I would argue quite the opposite: that the xanthogranuloma derived from the colloid cyst and extended into the choroid plexus. Indeed, Dr. Peter Burger and colleagues write in the fourth edition of Surgical Pathology of the Nervous System and Its Coverings that "a xanthogranulomatous reaction occasionally supervenes in colloid cysts, largely replacing the epithelium in some cases."

Cool case.

Neuropathology Focus of New SNO President's Address Today

2011-11-18T15:14:00.001-06:00

Over 1400 attendees at 2011 SNO meeting in Anaheim

Dr. Aldape discussed brain tumor biomarkers

Same view as above, at 40X

Neuropathlogy took center stage at the Society for Neuro-Oncology (SNO) meeting today as Dr. Kenneth D. Aldape, neuropathogist at the University of Texas MD Anderson Cancer, was introduced as the next president of the society. Dr. Aldape also delivered an address to more than 1400 attendees about the future of surgical neuropathological reporting. Aldape's research centers on the clinical utility of brain tumor biomarkers as prognostic indicators. He described how the use of biomarkers will change the way surgical neuropathology diagnoses are rendered. He noted that the broad morphologic spectrum one sees in gliomas makes the recommendations of the World Health Organization sometimes difficult to implement. For example, the difference between a WHO grade II and grade III astrocytoma is based principally on whether or not mitotic figures are "brisk" as interpreted by the examining neuropathologist. Yet, the imprecision of that approach is obvious when one considers variables such as the diligence of the neuropathologist in identifying mitotic figures, the often equivocal morphology of apoptotic-versus-mitotic cells, as well as the variable technical quality of tissue processing and staining. The use of biomarkers will make diagnoses more reliable and will provide more useful prognostic information to the oncologist. Dr. Aldape projected onto the screen an example of a recent surgical pathology report he had generated at MD Anderson. The report highlighted the status of the several biomarkers, including G-CIMP, IDH1, pHH3, MIB1, 1p/19q deletion, and MGMT. Then, only in the last sentence of the comment, was it noted that the histology and biomarker profile was most consistent with a WHO grade III (anaplastic) astrocytoma. It was as if the WHO diagnosis and grade were a perfunctory afterthought. Finally, Aldape noted that biomarkers will become even more important in the coming years as biomarker data becomes "actionable", allowing the oncologist to personalize the treatment of a particular tumor depending on the biomarker profile. These are exciting times....

Kois, Perry, Giannini, and Zagzag Among Neuropathologists at SNO Meeting

2011-11-17T13:30:00.001-06:00

Neuropathologists are well represented at the Society for Neuro-Oncology (SNO) meeting going on here in Anaheim, California. Today I ran into Dr. Arie Perry of UCSF and was pleased to make the aquaintence of Dr. Nancy Kois of St. Alphonsus Hospital in Boise, ID.

Drs. Arie Perry and Nancy Kois today at the SNO meeting in Anaheim, CA

I had a chance to catch up with the Mayo Clinic's Dr. Katerina Giannini who is in attendance this weekend. I also just ran into NYU's Dr. David Zagzag, who confirmed that his institution is actively seeking a neuropathologist. Anyone interested in the position can email him at dz4@nyu.edu.

SNO is coming down in Southern California!!

2011-11-16T23:05:00.001-06:00

For the next couple of days, I'll be blogging live from the 16th annual meeting of the Society for Neuro-Oncology (SNO) in Anaheim, California. SNO is the most inter-disciplinary of the neurologic societies, with membership that includes neurosurgeons, neuro-oncologists, neuropathologists, radiation oncologists, neuroradiologists, pediatricians, laboratory scientists, nurses, and other specialists. According to a report from SNO's membership committee, a full 5% of SNO membership comes from the specialty of pathology. I am among that 5%. SNO's acknowledgement of the pivotal role neuropathology plays in brain tumor research and treatment is exemplified by the fact that this year the society has recognized a neuropathologist -- Kenneth Aldape, MD from the University of Texas MD Anderson Cancer Center -- as recipient of the Victor Levin Award in Neuro-Oncology Research. I'll be in attendance on Friday when Dr. Aldape receives the Levin Award and delivers a plenary session on tumor genetics. SNO has further recognized neuropathology by including "pathology" among the nine Young Investigator Round Table career interest luncheons. Finally, in reviewing the abstracts from the meeting, I see that several posters include neuropathologists among the authors. Although most of these authors are placed in other specialty categories in the abstract book, there is actually a distinct section devoted specifically to pathology. The senior author of one of the posters in the pathology section is a neuropathologist whom I have described previously in this blog as a "rising star in the neuropathology firmament": Craig Horbinski, MD, PhD. Dr. Horbinski's abstract is entitled Glioblastoma Survival Varies According to Degree of EGFR Amplification.

The outgoing president of SNO, Frederick F. Lang, MD, writes in the latest issue of SNO News that one of the goals of his presidency has been to "extend a cooperative hand to other like-minded organizations in the USA and internationally. The wisdom of SNO is its inclusion of multiple disciplines, and I have always thought that other organizations should benefit from this wisdom." In the spirit of this multidisciplinary approach, SNO has partnered this year with the Section of Tumors of the American Association of Neurological Surgeons (AANS) and Congress of Neurological Surgeons (CNS). I would urge the American Association of Neuropathologists (AANP) to consider partnering with SNO to create a joint meeting. A productive cross-pollination would undoubtedly result.

Keep reading this blog over the next couple of days as I report on the interesting educational and research presentations that will occur as SNO comes sunny Southern California!

MD/PhD Student Seeks Advice About a Career in Neuropathology

2011-11-10T16:21:00.001-06:00

I recently received an inquiry from a medical student named Stephen Briggs. Rather than pontificate on this topic myself, I am posting, with his permission, Stephen's email with hope that the readership of this blog might offer some advice to this young man in the comment section of this post. Thanks in advance to anyone who would like to put in their two cents' worth.

Stephen Briggs

DearDr. Moore,
I have been avidly following your blog for a while now, and I would liketo ask you a few questions about the field of neuropathology. I am an MD/PhDstudent, currently in the PhD phase of my training. I am researchingneurological disease, and I want to continue in this field. I am stillrelatively early in the program (I just finished the first year of my PhD), butI would like to start thinking about possible future directions. Neuropathologyseems to be a great fit based on my interests, but I would like to discuss someof the details with you.
First, you have mentioned in some posts that a neurology residencyfollowed by neuropathology is no longer the standard pathway (September 2010 guest post). Is it actually a disadvantage? If I want to do neuropathologywork, should I plan to go through pathology? The guest poster (Dr. John Donahue) seemed to think that the neurology to neuropathology was a long shotfor new students, because most departments want a more general pathologistinstead of a total specialist in neuropathology.
Second, I was interested in your take on research in neuropathology. To anoutsider, it seems particularly well suited: it includes predictable workhours, access to human tissue, and a generally academic mindset. Is the actualpractice different? Are there any challenges to pathology research that I maynot be aware of? If I chose to do research in neurology instead, would it besubstantially different?
Finally, I am interested in the long-term prospects of the field. Icount fully 20 openings posted on your blog, which certainly seems hopeful.However, from searching on Google I have seen horror stories about howdifficult it can be to get into the field of pathology in general. Somepathologists report taking fellowship after fellowship to avoid beingunemployed while waiting for a position to open up. Also, some residents wereworried about the field as a whole, as it is easier to computerize or outsourcethan other fields of medicine. Are these concerns justified?
Thank you for maintaining your blog. I am glad that there is a resourcefor students to find out a little about neuropathology, and to feel connectedto the field as it evolves.
Stephen Briggs

Best Post of May 2011: The Timeless Dr. Adelman

2011-11-06T12:00:00.001-06:00

The next in our "Best of the Month" series comes from May 20, 2011:

Lester S. Adelman, MD

I was recently sent this 1992 essay written by Dr. Lester S. Adelman, retired neuropathologist at Tufts New England Medical Center. It amusingly illustrates the anonymity in which we pathologists toil:

Pathologists spend their time in the figurative,
and sometimes literal bowels of the hospital.
Even those of us who specialize in the pathology
of the brain occupy this nether region. The
patients who benefit from our brilliant diagnoses
are often as little aware of us as they are of
the hospital laundry.
This life of anonymity has its rewards. Frozen sections
are only rarely done on nights and weekends, and straightforward
cases are disposed of quickly. The intellectual and
visual pleasures of the job are great. Every once in a while,
however, we are reminded of the fact that we have given up
a part of doctoring, the part that has to do with knowing the
gratitude of the patients whom we help.
Some years ago, in the era before CT scans and MRIs,
a patient was admitted to our hospital with a brain tumor.
Preoperative radiologic diagnoses in those days were based
on angiography, and this patient's angiogram strongly suggested
a glioblastoma multiforme. The patient was given the
bad news, and a biopsy was done to confirm the diagnosis.
The surgeons also thought the tumor was a glioblastoma,
but when I looked at the frozen section, I discovered the
tumor was clearly a meningioma. With this diagnosis, the
surgeons were able to find a plane of dissection around the
tumor and remove it completely.
I was happy with the outcome and thought I had accepted
the fact that the patient would never know my part .
in it. It was not long after that I was to come face-to-face
with the shortcomings of my chosen medical specialty.
A week later I was at a conference with the neurosurgeons
when I noticed that one of the residents was wearing
an expensive new wristwatch. A moment later I noticed that
a senior neurosurgeon had a similar watch on his wrist. A
quick check of the audience revealed that they all had new
watches!
"What's going on?" I asked.
"You remember Mr. X, the patient with the meningioma?
He's a jeweler, and he was so happy he didn't have
a glioblastoma that he gave us all new watches."
"How about me?" I whined. "I'm the one who cured
him. If it weren't for me, you would have quit, thinking he
had a glioblastoma."
The physicians smiled graciously and conceded this was
probably the case.
Years have passed, and despite the advances in imaging,
my neurosurgical colleagues continue to consult me about
diagnoses. But when I want to know what time it is I still
consult my Timex.

Dr. Doug Anthony becomes Chief-of-Pathology at Brown-affiliated hospitals

2011-10-28T12:28:00.002-05:00

Excerpts from a message from Timothy J. Babineau, MD, President and Chief Executive Officer, Rhode Island Hospital and The MiriamHospital

We are pleased to announce theappointment of Douglas C. Anthony, MD, PhD, as chief of pathology at RhodeIsland Hospital and The Miriam Hospital, effectiveFebruary 1, 2012. A neuropathologist, Dr. Anthony will lead theclinical, educational and research pathology programs for Lifespan, as well ashelp to bridge pathology and the neurosciences through the Norman PrinceNeuroscience Institute.

Douglas C. Anthony, MD, PhD

Dr. Anthony comes to Rhode Island Hospital from theUniversity of Missouri, where he is the chair of the department of pathologyand anatomical sciences and professor of neurology. At the University ofMissouri Health Care he serves as chief of pathology and medical director ofpathology clinical laboratories. He also serves as a pathologist at the HarryS. Truman Veterans Administration Medical Center, Women and Children’sHospital, and the Ellis Fischel Cancer Center, and as a neuropathologist forthe Office of the Medical Examiner in Boone, Callaway and Greene counties inMissouri. Previously, he was on the faculty at Harvard Medical School andserved as a neuropathologist at Boston Children’s Hospital, Brigham and Women’sHospital, and as a neuropathologist consultant to the Office of the ChiefMedical Examiner for the Commonwealth of Massachusetts.

He has won numerous awards, including the Dr. Edison H.and Sallie Y. Miyawaki Teaching Award in Neurosciences at Harvard MedicalSchool; the Excellence in Education Award in pre-clinical sciences at theUniversity of Missouri; and the Order of Socrates award at the School ofMedicine at the University of Missouri.

Dr. Anthony’s appointment furtherdemonstrates our commitment to becoming a leader in the neurosciences, and weare confident that he will be a tremendous asset to our clinical team. Please join me in welcoming and congratulating Dr. Anthony.

NIH Loan Repayment Program a godsend for young neuropathologists interested in research

2011-10-26T13:58:00.000-05:00

Today I feature a guest post from the illustrious Dr. Mike Lawlor.

Hi Everyone,

I'd just like to tell everyone about a programthat the NIH offers, which may be of great interest to Neuropathology Fellows,Research Fellows, and Junior Faculty. It's called the NIH Loan RepaymentProgram (LRP), and it's designed to encourage people with an interest inresearch to remain in the academic research environment. From what I'veheard, the NIH created this program so that people with lots of student loans(mostly medical doctors) with an interest in research would not give up theirresearch careers due to their loan debt.

I just got an email from the LRP people, andthey now have a webinar available to help people apply. The link for thewebinar is: http://bit.ly/nihlrptutorial

Michael W. Lawlor, MD, PhD

The award offers up to $35,000 per year for up to twoyears, and you're able to apply for renewals whenever it runs out. Thiscounts as income, but the NIH also pays the federal income tax on this grantfor you. I ended up owing about $2000 in state tax every year forhaving the award, but that doesn't seem like much as you watch your studentloans disappear.

Here's what you'll need:

1) The grant application, which can be found this site. The forms aren't too labor-intensive, and you need topropose a 2-year research program and be able to guarantee a 50% effortcommitment to the research.

2) A bunch of info on your student loans,most/all of which can be found on your monthly statements. Your studentloan burden needs to exceed a certain amount before you qualify, and the amountyou need is dependent on your income. Given the non-stellar income ofmost neuropath fellows and research fellows, it's actually pretty easy toqualify on financial grounds. You may continue to apply for renewals as long as you continue to meet the eligibility requirements.

3) Someone to vouch for you. Your research adviser will need to reply to an email that confirms that you are devoting 50%effort to your research every quarter. After that confirmation is made,and you confirm that the prior payment made it to the right account, they applya payment to your educational loans.

Anyway, I've been in this program for the past 2years, had it renewed for another year, and am in the process of writinganother renewal. It really is a fantastic program with excellent support. The next deadline is November 15th, so there's definitely time for youguys to put something together. Once you submit the application, you'llhear nothing for about 6 months, and then they'll ask you for some updatedstudent loan information if you've made it through their scientific reviewprocess. The application cycle is once per year.

I hope that this helps some of you, and goodluck!

Thanks for this helpful information, Mike!

Treatable Neurological Disorders Misdiagnosed as Creutzfeldt-Jakob Disease

2011-10-17T19:04:00.000-05:00

A case of primary CNS angiitis thought to be sCJD

Dr. Mark Cohen and a team of workers at Case Medical Center in Cleveland, Ohio have published an important article in the Annals of Neurology entitled Treatable Neurological Disorders Misdiagnosed as Creutzfeldt-Jakob Disease (Ann Neurol 2011;70:437–444). Why is this article important? Well, because mistaking a survivable, treatable disorder for a fatal, non-treatable disorder is not optimal. Cohen's team reviewed the pathologic diagnoses of 1,106 patients who were referred for potential prion disease to the National Prion Disease Pathology Surveillance Center (NPDPSC) at Case Western Reserve University from 2006 to 2009. About one-third of the cases did not have prion disease, with Alzheimer disease and vascular disease being the most common conditions accounting for dementia. Further, about one-quarter of the non-prion cases had treatable diseases, including immune-mediated disorders, neoplastic disorders such as lymphoma, as well as infectious and metabolic disorders. The immune-mediated disorders included primary angiitis of the CNS, acute disseminated encephalomyelitis, limbic encephalitis, neurosarcoidosis, paraneoplastic cerebellar degeneration, and one case of Wegener granulomatosis. Of note, more than half of patients with a treatable dementia had a positive CSF 14-3-3 protein test, highlighting the danger of relying too heavily on this test in making a diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD). It turns out that the most specific test for distinguishing CJD from other diseases was magnetic resonance imaging. Drs. David Perry and Michael Geschwind, in a review of this study in the September 2011 issue of Nature Reviews Neurology, (Perry, D. C. & Geschwind, M. D. Nat. Rev. Neurol. 2011:7, 479–480) write: "The fact that many of the non-prion diagnoses in the present study were potentially treatable RPDs [rapidly progressive dementias] should prompt thorough diagnostic testing in patients who are suspected of having sCJD, in order to rule out mimics. The use of CSF testing, contrast-enhanced MRI, and autoimmune antibody screening is supported by this study."

Attractive Neuropathology Postdoc Position in Neurodegenerative Disease Now Available at UCSF

2011-10-10T18:11:00.002-05:00

Lea T. Grinberg, MD, PhD.

I recently received an email from Lea T. Grinberg, MD, PhD, a neuropathologist originally from Sao Paulo, Brazil now working at UCSF. She is recruiting a postdoc to work with her. Dr. Grinberg specializes in aging and neurodegenerative diseases and was recently awarded an R01 grant to study early stages of ADand FTLD-TDP in postmortem human tissue. She has access to a large brain bank associated with the Brazilian Aging Brain Study Group as well as the UCSF Memory and Aging Center brain bank. The postdoc will learn state-of-the-art methods for studying human post mortembrains, such as stereology, immunohistochemistry and fluorescence, computerassisted 3D reconstruction, and whole brain processing. She writes of the UCSF Memory and Aging Center: "We are a team of 150 individuals and the divisionpromotes weekly grand rounds, journal clubs, lab meetings and regular CPCsessions. I believe it is an excellent opportunity for a youngneuropathologist aiming to have a career in neurodegenerative disease."

I would say so! Here's the official job listing:

Post Doctoral Position inNeurodegenerative Diseases

NIH-supported post-doctoral position is immediately available for aqualified and highly motivated researcher to study early stages ofneurodegenerative disease in human postmortem tissue

The fellow willpursue a series of related experiments regarding brain areas involved in veryearly clinical stages of Alzheimer’s disease and frontotemporal dementia. Thesuccessful candidate will have access to very difficult to get tissue belongingto cognitively normal elderly who already showed neurodegenerative changes inthe brain. In addition, the fellow will be trained in state-of-the-artneuropathological/neuroanatomical processing and sophisticated graphic andreconstruction software. The fellow will have the opportunity of furtherparticipate in ongoing experimental studies.

PreferredQualifications
Strong interest in neurodegenerative disease

Training in quantitativeneuropathology or neuropathology is a plus.

This project is part of a close collaboration with other groups;therefore, candidates must have the ability to work in an international team,show organizational skills, and be driven by an interest in a multidisciplinaryresearch setting

Applicants should possess arecent (within last three years) MD or PhD degree in theneuropathology/neuroanatomy/ neurosiciences with strong experience instereology.

Applicantsshould send a CV and 3 letters of recommendation to Dr. Grinberg lea.grinberg@ucsf.edu

Bernd Scheithauer Has Died

2011-09-21T10:17:00.003-05:00

A very sad letter from the Mayo Clinic received today:

Subject: BerndScheithauer

I just learned that Bernd Scheithauer, mytreasured friend and colleague with whom we all had worked clinically or in thelaboratory, was found dead at his home today. He was not feeling well atwork yesterday, and apparently died of natural causes at his home last eveningor this morning.

Bernd was a rare individual and an academic giant.

Bernd had a deliciously naughty sense of humor and --with 24 indexed articlesalready in print this year-- I can just see him looking down on us, giggling,and saying, "Bill, take notice; publishing and perishing are not mutuallyexclusive."

I will certainly miss him.

Bill

William L. Lanier, M.D
Editor-in-Chief
Mayo Clinic Proceedings
Rochester, Minnesota USA

Fusiform gyrus key to understanding neuroanatomic basis of Capgras delusion

2011-09-20T18:45:00.000-05:00

Thanks to Doug Shevlin, MD (pictured with crawdaddy) for steering me toward this TED talk by neuroscientist Vilayanura Ramachandran, MD, PhD. Dr. Ramachandran discusses the neuroanatomical substrate of the Capgras delusion, a neurological deficit about which I have blogged before. Dr. Ramachandran explains that the origin of this fascinating deficit stems from a severing (typically resulting from a stroke or neurodegenerative disorder) of the connection between the fusiform gyrus (the face perception area of the brain) and the amygdala (which gages the emotional significance of a perception). Good stuff.... including the crawdaddy.

THE 5 HOTTEST TOPICS IN NEUROPATHOLGOY TODAY

2011-09-13T11:58:00.001-05:00

By consensus, I present to you the five hottest topics in neuropathology today:

1. Chronic Traumatic Encephalopathy - There is an emerging recognition of CTE among those who have played contact sports. The elucidation of CTE will continue to have major public health policy implications.

2. Molecular Subtyping of Brain Tumors - For example, determination of the presence of O(6)-methylguanine DNA methyltransferase (MGMT) activity as a prognosticator of response to alkylating chemotherapy in gliomas is becoming increasingly important to our clinical neuro-oncology colleagues. Other molecular tests that are gaining popularity include IDH1 and EGFR. Molecular profile panels will become the standard of practice in the coming decades.

3. Brain Tumor Stem Cells - Questions about their existence and potential as targets for therapy have energized neuro-oncologic research.

4. Role of Microvascular Disease in Expression and Pathogenesis of Alzheimer Disease - The concept that Alzheimer disease may have a vascular pathogenesis may radically change the way the disease is prevented and treated.

5. Molecular Developments in Frontotemporal Lobar Degeneration - As UCSF neurologist Bruce Miller, MD said: "Classification of FTLD is moving from a syndromic approach toward one based upon neuropathology and genetics." In particular, the description of the TDP-43 proteinopathies has had a major impact on our understanding of a previously unrecognized form of dementing disease.

There you have it. Thank you to everyone who contributed to this list. I think that it will help raise our collective eyes to the horizon.

What are the five hottest topics in neuropathology today?

2011-09-06T13:52:00.000-05:00

What are the most promising or exciting topics in neuropathology today? Put up your list in the comments. Off the top of my head, in surgical neuropathology, the discussion regarding the utility of MGMT testing on high-grade gliomas (and whether PCR or IHC means of analysis) appears to be a timely topic. In non-surgical neuropathology, Chronic Traumatic Encephalopathy has been in the news lately. And what about TDP-43 protein in FTLD and MND? Come up with your own list and place in the comments. If we, as a virtual community, can come up with five of the most provocative topics in the field, I'll put them up on my next post.