Sleepless

Neuropathologist Henry Brown, MD, PhD (pictured) recommends the novel Sleepless by Charlie Huston to those in the neuropathology community with an interest in the fatal insomnias. A review on Amazon.com describes the book as a "thriller set in a postapocalyptic Los Angeles, [where] a devastating illness renders the afflicted unable to sleep. In about a year, those with SLP (as the sleepless illness is known) deteriorate and die." Dr. Brown says that the novel may be "a little out there for some of our neuropathologists, perhaps", but a good read nonetheless.

2010 AANP Diagnostic Slide Session diagnoses revealed

For those of you who missed this evening's diagnostic slide session, here are the diagnoses that were ultimately revealed:

1. Phosphaturic mesenchymal tumor, mixed connective tissue variant
2. Primary Solitary Amyloidoma
3. CNS parenchymal involvement by Kikuchi-Fujimoto disease
4. Teratoma with malignant transformation
5. Progressive Multifocal Leukoencephalopathy with Immune Reconstitution Inflammatory Syndrome
6. Varicella Zoster Virus meningitis with intraparenchyal hemorrhage
7. Aneurysmal hemorrhage due to isolated intracranial giant cell arteritis
8. Canine distemper viral encephalitis in a Bengal tiger
9. Feline spinal cord leukomyelopathy secondary to consumption of irradiated dry food diet
10. Acute Hemorrhagic Leukoencephalitis (Weston Hurst disease)
11. Frontotemporal lobar degeneration with ubiquitin proteasome system inclusions (FTLD-UPS) with cerebellar involvement
12. Neimann Pick type C1 disease (compound heterozygote)

As you can see, it was the usual array of simple diagnoses!!!

Two more neuropathology job opportunities listed on announcement board at annual AANP meeting

Dr. Harry Vinters (pictured), in a conversation I just had with him in the refreshment area at the annual AANP meeting, told me that when a trainee complains about the paucity of jobs in neuropathology, he simply refers them to Neuropathology Blog! As you can see in the job listings section of this blog, opportunities for clinical neuropathologists are abundant -- as long as you are willing to relocate. I just checked the announcements bulletin board at the meeting, and discovered two new jobs that I am only now adding to the blog job posting list. Dr. Adekunle Adesina at Texas Children's Hospital/Baylor College of Medicine is looking for a neuropathology faculty member. He can be reached at amadesin@texaschildrens.org. Also, Dr. Steven Chin of the University of Utah in Salt Lake City is seeking a neuropathologist at the assistant or associate level. Dr. Chin can be reached at steven.chin@path.utah.edu. Happy hunting!

86th Annual AANP Meeting: Rapamycin as a possible treatment for tuberous sclerosis

Drs. David Louis (AANP president) and Anat Stemmer-Rachamimov put together a nice day-long educational session today to kick off the American Association of Neuropathologists annual meeting here in Philadelphia. In addition to our own kind, non-neuropathologists were brought in to give their persepctives on these syndromes. For instance, Dr. Elizabeth Henske (pictured), an oncologist, talked about the spectrum of clinical manifestations seen in tuberous sclerosis complex (TSC) and experiemental therapeutics based on understanding the molecular underpinnings of the syndrome. Given that the genes mutated in tuberous sclerosis (TSC1 and TSC2) inhibit mTOR, Henske said that researchers are looking into the use of rapamycin, an inhibitor of mTOR, as a treatment for not only the more obvious manifestations of TSC, such as subependymal giant cell astrocytoma, but even for reversing learning deficits in children with TSC. In a mouse model of TSC in which there is no pathological evidence of brain lesions, it was discovered that these mice have cognitive defects as evidenced by water-maze testing. "And the thing that just gives me shivers to think about," says Henske, "is that these cognitive deficits are correctable with rapamycin. Five days of rapamycin! So that has caused a big shift in the thinking about children with tuberous sclerosis who have cognitive defects and many parents are actually putting their children on rapamycin off-trial, but we would really like to do a cognitive trial and figure out whether there is benefit in children with tuberous sclerosis who are taking rapamycin. The parents, many of them, have very compelling anecdotal studies of improvement in their childrens' learning or behavior." Therefore, Dr. Henske will be working on an efficacy and safety trial, with funding from the Tuberous Sclerosis Alliance, to see if rapamycin can improve cognitive function in these children. "If there is benefit with rapamycin neurocognitively, it would just be wonderful."

American Association of Neuropathologists happens next week

The American Association of Neuropathologists' annual meeting will be held in Philadelphia next week -- from June 10 to June 13. I'll be there -- blogging live -- with comments from participants, summaries of cutting-edge presentations, and news from the world of neuropathology.  Among the offerings will be a lecture on Autoimmune Synaptic Encephalitis by Dr. Josep Dalmau (pictured) of the University of Pennsylvania. Numerous other presentations are planned, including the Presidential Symposium, entitled: "Big Science" and the Transition to Personalized Medicine: How Can Neuropathologists Play a Role in Large-Scale Clinical, Translational and Basic Research?  I myself will appear at a panel on Friday the 11th at the trainee luncheon, where I'll be talking about landing your first job. I'll be joined on the panel by Dr. Suzanne Z. Powell who will discuss neuropathology training and Dr. Tony Yachnis who will talk about mentorship and sustainability. I look forward to the event and to meeting a few Neuropathology Blog readers along the way!

GBM with adenoid features

I came across a glioblastoma today (see below) which focally exhibited epithelioid and even gland-like features -- or what the WHO Tumor book calls "adenoid" characteristics. Had there not been other areas showing more classic GBM histomorphology, I'd have been obliged to order an immunohistochemical panel including melanoma and carcinoma markers.

Alzheimer patients to get nerve growth factor directly injected into brain

The Alzheimer’s Disease Cooperative Study, a 19 year project funded by the NIA, has embarked on a clinical trial that delivers Nerve Growth Factor (NGF) directly into the brain as a possible treatment for Alzheimer’s.

 

A Phase II clinical study of Ceregene's CERE-110, a gene therapy product designed to deliver nerve growth factor (NGF) to the brain for the treatment of Alzheimer's disease (AD) is currently in progress.

This Phase II study is a randomized, double blind, placebo-controlled trial and employs gene therapy to deliver nerve growth factor (NGF) directly into the brain. The rationale behind this study is that NGF is known to promote survival of cholinergic neurons, that degenerate in AD, and therefore may provide sustained functioning of these neurons. Direct delivery of CERE-110 into the brain aims to selectively target the Nucleus Basalis of Meynert (NBM), where cholinergic neuronal degeneration occurs in AD.

A Phase I study at Rush University and the University of California San Diego indicated that a single administration of the therapy was generally safe and well tolerated. The Phase I participants underwent cognitive testing, measures of activities of daily living, MRI scans and PET (positron emission tomography) scans. Increases in brain metabolism were observed in several cortical regions of the brain at six months and 12 months in some of the subjects, as compared to other severity-matched individuals with AD, suggesting a potential reversal of patterns typically observed in AD.

This Phase II study will examine the safety and effectiveness of NGF on Alzheimer's disease in 50 patients at 11 research sites throughout the United States. All eligible participants will be randomized equally to one of two treatment groups: half of the subjects will initially receive placebo surgery, but no administration of gene therapy. In the other half, CERE-110 will be injected into the NBM of the brain. At the completion of the trial, subjects in the placebo arm will be given the opportunity to switch to the active treatment protocol if the efficacy and safety data are supportive.

For more information go to: http://www.adcs.org/Studies/NGF.aspx  or  http://www.alzheimers.org/clinicaltrials/fullrec.asp?PrimaryKey=308

Best Post of December '09: Doug Miller's Modern Surgical Neuropathology: "a rarity in medical publishing in the 21st century"

The next in our series of "Best Posts of the Month" is from December 17, 2009:

Modern Surgical Neuropathology by Dr. Doug Miller (pictured) was reviewed by Dr. Leroy Sharer in last month's Journal of Neuropathology and Experimental Neurology. (I published a post on this book in June of this year.) Dr. Sharer points out that Dr. Miller's book is extraordinary in that it is penned by a single author -- "a rarity in medical publishing in the 21st century", writes Sharer. Some may take issue with Dr. Miller's fiercely independent perspective on surgical neuropathology, but one must respect his courage to say what he thinks. He is not afraid to challenge mainstream concepts. For instance, in his review, Dr. Sharer notes that Dr. Miller "devised his own tumor grading and classification schema, which he relates to others in use, particularly the World Health Organization system from 2007". If more neuropathologists had the chutzpah to put their perspectives out in the public arena for debate, it would undoubtedly invigorate the field!

Free samples of IDH1, the next big thing in glioma IHC, is now available

Dianova, the German company that makes anti-human IDH1 antibody for use in immunohistochemical staining of gliomas versus gliosis, is providing free samples of its product. Just go to the site, click on "free sample", and make a request via email. This marker may well be a tremendous advancement in distinguishing reactive astrocytosis from diffuse astrocytoma, so I would encourage you to get your free sample! Thanks to Drs. Craig Horbinski and Ty Abel for assisting me in discovering this opportunity.

What's the diagnosis?

After examining this photomicrograph of a section taken from the hippocampus at autopsy, write your diagnosis in the comment section. I'll post the correct diagnosis on Monday (May 10). Good luck!

Another Neuropathologist Heads West

Dr. Alexander Judkins (pictured), currently a neuropathologist at the Children's Hospital of Philiadelphia, is moving to sunny California to become chair of  pathology at Children's Hospital of Los Angeles. Judkins joins another neuropathologist transplanting to the Golden State: Dr. Arie Perry leaves Washington University in St. Louis next month to take a job at UCSF.