Webcast of craniotomy for skull-base mass in a 30-year-old female

The Virtual Brain Tumor Board, a service of Methodist University Hospital in Memphis, Tennessee, is currently featuring a 4-minute webcast depicting a craniotomy for removal of a large, skull-base meningioma in a 30-year-old female. The presentation is bookended by pre- and post-operative MRIs. Also on the site is a 11-minute pre-operative tumor board discussion of the case, including clinical presentation and options for surgical approach. This is just one of several cases presented on the site. I don't know that any other neurosurgical program in the country provides this kind of internet coverage of its cases. (You need to register and get a password before viewing the material on the site.)

Web tools for neuropathology addressed in recent Brain Pathology article

Neuropathology Blog was mentioned in a recent Brain Pathology article by University of Oklahoma neuropathologist Kar-Ming Fung (pictured) and University of California San Francisco neuropathologist Tarik Tihan. Entitled Internet and World Wide Web-Based Tools for Neuropathology Practice and Education (April 2009, 19:2, p 323-331), the article also features Dr. Fung's own extensive website, NeuroLearn.com, which is a self-guided neuropathology teaching tool for students and residents.

A child presenting with lack of coordination and a basal ganglia lesion

An 8-year-old girl presented with lack of coordination of the right arm and leg progressing over the course of six months. Occasionally, the girl would hold her right arm in a postured decorticate position when she would run; and she would suffer frequent falls when playing. Physical examination showed right-sided hemidystonia and rigidity. An MRI revealed a lesion:

The initial differential diagnosis of this tumor included primary CNS lymphoma, given the tight lymphocytic clustering in and around blood vessels (blue aggregation on the right):

However, the young age of the patient would make the diagnosis of CNS lymphoma less likely. Closer inspection also revealed the presence of scattered larger round cells with prominent nucleoli (center of the photomicrograph below):

These cells may be dismissed at first as native basal ganglia neurons. But their pleomorphism and haphazard distribution raises the specter of neoplasia. A childhood tumor that typically induces a flagrant inflammatory infiltrate in the setting of plump cells with prominent nucleoli is the germinoma. Subsequent positive immunohistochemical staining of these plump cells with placental-like alkaline phosphatase (PLAP) confirmed the diagnosis of germinoma in this case:

Germinomas typically arise in the pineal gland or suprasellar region; but loci away from the midline, as exemplified in this case, represent at least 10% of cases. Germinoma is the most common of the germ cell tumors of the central nervous system, but one is obligated to search a putatively unadulterated germinoma for other elements (such as yolk sac tumor, choriocarcinoma, and embryonal carcinoma) before bestowing the diagnosis of pure germinoma. Treatment for pure germinoma often gives gratifying results, as it is potentially curable with platinum-based chemotherapy and low-dose radiation. Survival rates approach 100%, even when local recurrence requires salvage therapy.

References:

1. Rosenblum MK. Chapter 28: “Neuromuscular System: Central Nervous System” in Rosai and Ackerman’s Surgical Pathology (Juan Rosai, editor). Mosby. 9th Edition (2004) pp. 2582-2584.

2. Ellison D, Love S, Chimelli L, Harding BN, Lowe J, Vinters HV. Neuropathology: A reference text of CNS pathology. Mosby. 2^nd Edition (2004) pp. 680-682.

3. Douglas JG, Rockhill JK, Olson JM, Ellenbogen RG, Geyer JR. Cisplatin-based chemotherapy followed by focal, reduced-dose irradiation for pediatric primary central nervous system germinomas. Journal of Pediatric Hematology/Oncology. January 2006. 28(1):36-9.

Dr. Katie goes to Med School: A nice blog for second year med students

Dr. Katie describes herself as "A 20-something girl trying to balance medical school and real-life". She has a nice blog addressing a variety of things, including issues concerning life as a second-year medical student. Today's post is on Twitter resources for those studying for Step 1 of the USMLE medical licensing boards. Good luck to Katie and everyone else taking Step 1 next month!

D. T. Max writes the back story on prion disease

Most of us accept the party line that there are three basic forms of Creutzfeldt-Jakob disease (CJD): acquired, inherited, and sporadic. The general neurology and neuropathology textbooks do not acknowledge that the very existence of sporadic CJD is controversial. But D.T. Max (picture from nytimes.com), in his book The Family That Couldn't Sleep: A Medical Mystery (2006), does not skirt this controversy. Some patient advocacy groups claim that CJD cases now classified as sporadic are in fact infectious. "A surprising number of mainstream scientists also doubt the existence of sporadic CJD -- among them protein experts, epidemiologists, and neurologists," Max writes. "Their objection is that sporadic CJD is an unnecessary idea. If a disease is known to spread by infection, why assume that some people also get it by chance? Why not find the infectious source in their cases as well? They see theoretical gaps in the idea of sporadic CJD theory too. For one thing, it is strange, if sporadic CJD comes about as a result of the body's declining ability as it ages to manufacture proteins correctly, that the chance of getting sporadic CJD goes down at around seventy years of age." Among the sporadic CJD doubters is none other than D. Carleton Gajdusek, who in 1976 shared a Nobel prize for his work in tracking the cause of kuru (a disease later classified among the prion disorders) as resulting from the practice of funerary cannibalism among the Fore tribes in New Guinea. Of course, in 1976, the word prion had not yet been invented. It took Stanley B. Prusiner, who himself won the Nobel in 1997 for his discovery of prions as a new biologic principle of infection, to come up with that catchy term. But Gajdusek (who died this past December) never took to the term "prion", preferring to call the infectious proteins "nucleating amyloids" -- in large part because of his rabid animosity toward Prusiner. Gajdusek addresses Prusiner in this spicy journal entry made at the time of the announcement of Prusiner's award:

"I never heard a word of original thought from you nor read such ideas in anything you authored for which I did not recognize immediately its source, which you always went out of your way to obscure. You a heretic? You a martyr? You a defender of unacceptable ideas? Bullshit! You shrewdly jumped onto a bandwagon of creative ideas and experimental work and shrewdly got on to the winning cart, proclaiming outrageously in press and media it was yours! I respect you less and less as your despicable game succeeds and you bask in your coveted fame."

There is no doubt that the prejudice, jealousy, and ambition played a large role in both the development and elucidation of the prion diseases. D. T. Max has written a wonderful book about the fascinating history of this strange class of diseases -- including CJD, kuru, fatal familial insomnia, bovine spongiform encephalopathy, and scrapie. As the mysteries surrounding the prion diseases are further unraveled, the secrets behind the more common neurodegenerative diseases (which feature their own kinds of aberrant, aggregating proteins) may also begin to be revealed.

Best Post of March '09: What's the deal with subcortical U-fibers?

The next in our series of "Best Posts of the Month" is for March, 2009. I chose this one as the best of the month partly because of the interesting comments it elicited from Dr. Doug Miller. Here's the post from March 19th:



FrontalCortex.com features lots of neuropathology, including podcasts from one of our favorite neuropathologists, Dr. Mark Cohen. In a podcast on demyelinating diseases, Dr. Cohen clarifies questions I've long harbored about the so-called subcortical U-fibers. The photomicrograph above (from the textbook Neuropathology by Ellison and Love) shows a blue myelin stain of an adrenoleukodystrophy case where the subcortical U-fibers are spared. The following is a transcription of Dr. Cohen's insightful comments on this topic. I should first clarify that when Dr. Cohen talks about the subcortical U-fibers being the "slowest myelinating fibers within the nervous system", he is not talking about conduction velocity, but rather about how long they take during one's lifetime to get completely myelinated. OK, here's Cohen:

"As you read through either your textbooks or the literature on leukodystrophies, you'll inevitably comes across a statement which describes either preservation, or lack of preservation, of the subcortical U-fibers. The subcortical U-fibers are, as the name implies, myelinated fibers just at the junction of the gray matter and the white matter which travel in a tangential, rather than radial, fashion connecting areas of cortex to other areas of cortex. What's special about these U-fibers, and why they are either spared or not in leukodystrophies, is that they comprise the slowest myelinating fibers within the nervous system. These U-fibers begin myelination early in gestation and often aren't completely myelinated until the third or fourth decade of life. Therefore, leukodystrophies in which the pathology is dependent on myelin turnover will demonstrate relative sparing of these fibers as the turnover is extremely slow; while in leukodystrophies which depend on toxic damage to the oligodendroglial cell, subcortical U-fibers are as vulnerable as other myelinated fibers within the nervous system."

"Adams and Victor" is a must-have for neuropathologists too

I am not a neurologist; but as a neuropathologist, I work with them often. I find myself reaching for "Adams and Victor" as frequently as I do my pathology textbooks! As mentioned in a recent post about Dr. Ray Adams, the ninth edition of this text just came out. I have access to this book for free electronically through my medical library, but its so much easier to have a hard copy within reach. (I am not a technophobe; I just think that sometimes a tangible book is more efficient.) One more thing: the price for this book ($127 on Amazon) is ridiculously low given the incredible amount of information that is packed into the nearly 1600 pages.

Genentech is looking for a neuropathologist

Courtney Grafe of Genentech recently informed me of a neuropathology position at the South San Francisco-based company. It looks as though they want someone who can straddle the worlds of research and clinical neuropathology. It looks like a great job for the right person. Details from the Genentech website follow. Contact Courtney at grafe.courtney@gene.com for more details.

RESPONSIBILITIES:The neuropathologist is appointed within the Department of Pathology, which is embedded within the Research Organization. The neuropathologist works with scientists in the Neuroscience Department, and in the Research and Development Organization to ensure that strategies for the treatment and cure of neurological diseases are based on accurate analyses of pathogenetic mechanisms. Pathologists participate both as collaborators and leaders in the discovery, characterization, and preclinical development of novel products in Neuroscience. This can include participation on teams devoted to the development of predictive and prognostic markers. At Genentech, pathologists have access to cutting edge equipment and techniques, including laser capture microdissection, confocal microscopy, advanced imaging morphometry and tissue microarrays that complement histology, immunohistochemistry, immunofluorescence, and in situ hybridization analyses. For applicants with the qualifications to lead a research program, the position comes with staff for technical support and access to in-house core facilities for histology, clinical pathology, microscopy, antibody generation, and transgenic and gene knockout models. The department has strong ties with academic and clinical groups both in the US and abroad. Publication in peer-reviewed journals is expected.

REQUIREMENTS:
The position requires an earned MD or DVM, completion of post-graduate residency training in diagnostic pathology, appropriate Board Certification in Anatomic Pathology, subspecialty training in neuropathology, Board Certification in Neuropathology, and a track record of creative and independent scientific productivity in a neuroscience-relevant discipline. An earned PhD in a related field will be highly desirable but not required. We seek candidates who can interpret traditional diagnostic categories in the context of a detailed and current understanding of molecular and cellular biology of the central and peripheral nervous systems. Candidates must have demonstrated their ability to handle several projects at any given time, to work successfully in teams and to communicate clearly both verbally and in writing to a variety of audiences.

William "The Refrigerator" Perry hospitalized in serious condition due to complications of Guillan-Barré syndrome

According to an associated press report, the gargantuan defensive tackle William "The Refrigerator" Perry (pictured below), who helped lead the Chicago Bears to a 1985 Super Bowl victory, has been hospitalized after complications related to Guillan-Barré syndrome (GBS).


Perry remains in serious condition at Aiken Regional Medical Center, located in his boyhood home of Aiken, South Carolina. Perry's nephew, Purnell Perry, said Tuesday that his uncle was admitted more than a week ago but was expected to recover. According to thebrainmatters.org, a website of the American Academy of Neurology Foundation, GBS "can be a devastating disorder because of its sudden and unexpected onset. Most people reach the stage of greatest weakness within the first 2 weeks after symptoms appear, and by the third week of the illness 90 percent of all patients are at their weakest. The recovery period may be as little as a few weeks or as long as a few years. About 30 percent of those with Guillain-Barré still have a residual weakness after 3 years. About 3 percent may suffer a relapse of muscle weakness and tingling sensations many years after the initial attack."

According to Perry's agent, Adam Plotkin of NOPAC Talent Agency, Perry's GBS had developed into a chronic form known as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Depicted below is an electron photomicrograph of a transerve section of peripheral nerve involved with CIDP. Note the the thinly myelinated axons at the 3, 5, and 10 o'clock positions. Surrounding these axons are "onion-bulb" formations wherein multiple Schwann cells are concentrically arranged around inadequately myelinated axons.

Thanks to Mark B. Weiss of Earthwise Productions for alerting me to Perry's condition.

A quick question on brain regions affected by hypoglycemia

Here's a question from Neuropathology Review, 2nd edition, by Dr. Richard Prayson (Humana Press, 2008):

Hypoglycemic neuronal necrosis preferentially affects all of the following areas except:
A. Cortex - layers II and III
B. CA1 region of hippocampus
C. Dentate
D. Caudate
E. Purkinje cells

The answer appears as a comment to this post.

Beta-2 Transferrin: The Tau of Trauma

Jeannie Williams, a laboratory technician at Memorial Hospital in Springfield, IL, posed a question about beta-2 transferrin testing on cerebrospinal fluid (CSF). Because beta-2 transferrin is a normal constituent of CSF, but not of plasma or mucosal secretions, it is useful in determining whether a patient's nose or ear is leaking CSF versus some other fluid. This is important in determining whether an occult skull fracture or defect has opened a potential route of infection into the central nervous system. In addition to the CSF, beta-2 transferrin is present in the occular humors and the inner ear fluid, which could be an alternative source of this protein in trauma cases where the central nervous system is not actually breached.  In the hospital laboratory, beta-2 transferrin can be detected electrophoretically by immunofixation. Thanks for the question, Jeannie!

Sources:
Tietz Clinical Guide to Laboratory Tests, 4th Edition, Alan H.B. Wu (editor), Saunders Elsevier 2006, p. 1063-5.
Molecular Biology of the Cell, 4th Edition, Bruce Alberts, et al. (editors), Garland Science 2002, p. 935.