Friday, November 30, 2007

Innervation of the pineal gland

The pineal gland is innervated by the nervi conarii. This name was derived from the fact that an antiquated term for the pineal gland is the "conarium", which literally means "cone". The nervi conarii are sympathetic fibers with cell bodies situated in the superior cervical ganglion.

Wednesday, November 28, 2007

The arachnoid is a recent discovery

According to the Fuller/Goodman book, the meningeal arachnoid is a relatively recent discovery. Although the dura mater and leptomeninges were described as long ago as 200 BC by Galen, the discovery of an arachnoid portion of the leptomeninges was not made until AD 1664 by Dutch anatomist Fredrik Ruysch.

Monday, November 26, 2007

The Best Intro Neuropath Book

I've looked at several introductory neuropath books for use by residents rotating in neuropatholgy (these include neurologist only in my case, but some institutions have neurosurgeons and general pathology residents rotating with them as well). Well, these residents need a handy, simple reference text. I recommend Practcal Review of Neuropathology (by Greg Fuller and J. Clay Goodman). The one caveat is that the pictures are black and white, and not the best quality. That being said, I think the pictures are adequate to get the idea of what is being discussed. I have compared this book to the Prayson book, the Escourolle and Poirier book, and the most recent competitor by Haberland. Even though all these books have been published more recently, Fuller and Goodman is the best. I hope they come out with a second edition with color pictures. If so, they will CRUSH the competition.

Friday, November 23, 2007

Not all neuropathologists have their primary training in general pathology

J. Clay Goodman, M.D., Assistant Dean for Medical Education at Baylor, did a residency in neurology, not pathology, before getting fellowship training in neuropathology. Another prominenet neuropathologist, John E. Donahue, had a similar trajectory, having done a neurology residency at Tufts before doing a fellowship in neuropathology at Brown University in Rhode Island, where he is now an attending. Most of us, however, had general pathology training before becoming neuropathologists.

Wednesday, November 21, 2007

Abstract from journal Cell on stem cells

This is off topic, but there's big news today regarding the
creation of pluripotent cells from human skin fibroblasts.
Here's the abstract from the Yamanaka study in Cell:
"Successful reprogramming of differentiated human
somatic cells into a pluripotent state would
allow creation of patient- and disease-specific
stem cells. We previously reported generation
of induced pluripotent stem (iPS) cells, capable
of germline transmission, from mouse somatic
cells by transduction of four defined transcription
factors. Here, we demonstrate the
generation of iPS cells from adult human dermal
fibroblasts with the same four factors: Oct3/4,
Sox2, Klf4, and c-Myc. Human iPS cells were
similar to human embryonic stem (ES) cells in
morphology, proliferation, surface antigens,
gene expression, epigenetic status of pluripotent
cell-specific genes, and telomerase activity.
Furthermore, these cells could differentiate
into cell types of the three germ layers in vitro
and in teratomas. These findings demonstrate
that iPS cells can be generated from adult
human fibroblasts."

Tuesday, November 20, 2007

CNS Whipple disease

Somebody asked me the other day about CNS Whipple disease. I said that I thought it was an instestinal infection and didn't think it had a CNS manifestation. I thought wrong. Caused by Tropheryma whippelii, a gram positive intracellular actinomycete, Whipple disease of the CNS can cause various symptoms, including ophthalmoplegia.

Thursday, November 15, 2007

Final posting on the JNEN review article

The bottom line here is that although PD, DLB, and MSA are all synucleinopathies, they differ from one another in terms of composition of the inclusions. And, even among different patient there are differences in protein compostion of each inclusion (i.e., not all brainstem Lewy bodies are created equal). These are very complex issues that are far from being understood.

Tuesday, November 13, 2007

Yet more on the JNEN review article

Regarding brainstem Lewy bodies, here's something interesting from the article: "The ultrastructural similarities among filaments in LBs [Lewy bodies], pale bodies, and perikaryal threads prompted the hypothesis that AS [alpha-synuclein] perikaryal threads are an early stage of filament assembly that may then progress to pale bodies and, finally, to classic LBs."

Poll results

I see that no one voted in the poll. I suppose no one actually reads this blog. But, then again, most bloggers blog for reasons other than being read by others. In any case, my choice of a site for the AANP meeting of the four options is Little Rock, AK. When would you otherwise have a chance to go there?

Monday, November 12, 2007

More on the JNEN article

I was never clear on exactly which cells contained the glial cell inclusions (GCIs) in Multiple System Atrophy. This article clears that issue up. I quote: "GCIs are faintly eosinophilic, sickle-shaped, oval or conical inclusions that displace the nucleus eccentrically. Their localization to microglia has been established by double staining techniques." There you have it!

Friday, November 9, 2007

JNEN article on synucleinopathies

In the introduction to the article cited yesterday, the authors describe two subtypes of multiple system atrophy (MSA-P and MSA-C). What about the type in which primary autonomic failure is the predominant presentation? Does the dysautonomic subtype (formerly known as Shy-Drager syndrome) have a specific MSA subtype designation? And, where would one find neuropathologic evidence of disease in that subtype? That information is missing from the introduction. Given that this is supposed to be a review article, I would think that that aspect of MSA would be addressed.

Thursday, November 8, 2007

Protein aggregation in the synucleinopathies

The current issue of the Journal of Neuropathology and Experimental Neurology has a review article about alpha-synuclein aggregation mechanisms in the major synucleinopathies: Parkinson's disease, Dementia with Lewy Bodies, and Multiple System Atrophy. The article was written by Drs. Katrin Beyer and Aurelio Ariza from Barcelona, Spain. I'll have more to say about this article in future posts.

Wednesday, November 7, 2007

The problem with muscle biopsies in adults

By the time the adult patient comes to the point where they need a muscle biopsy, all other diagnostic maneuvers have been exhausted. Often, the biopsy is of little to no help and the clinician is left wondering what the diagnosis is. I often find muscle biopsies frustrating because I know that the patient had to undergo minor surgery to have the biopsy done, and then I cannot really do much with the biopsy to help the clinician. Part of it may be my own diagnostic limitations. But, I see the reports of other neuropathologists, and they are also often vague and non-specific as well. I suppose it is helpful when I can identify features consistent with polymyositis. But, when there is a clinical suspicion of polymyositis, what's the harm in a trial of steroids to see if the patient gets better? I realize that an unnecessary course of steroids is not worth the risk in some patients, but in many such a trial would be an acceptable route to go rather than subjecting the patient to biopsy.

Tuesday, November 6, 2007

Emerging drugs for the treatment of glioblastoma

Bevacizumab (Avastin) is an angiogenesis inhibitor that is being used in the treatment of glioblastoma multiforme (GBM). AQ4N (Banoxantrone) is a prodrug that becomes active in hypoxic regions (i.e., tumor) that is also being examined as a useful chemotherapeutic agent for GBM.

Monday, November 5, 2007

Muscle biopsy

Today I'm looking at a muscle biopsy from a 63-year-old female with muscle cramping and increased creatinine level. There appears to be a chronic inflammatory infiltrate surrounding scattered non-necrotic muscle fibers. This is most consistent with polymyositis. I suppose, given the prefix "poly", that by definition polymyositis is in more than one muscle. So, given that I have a single biopsy of a single muscle, I can only claim that these histologic findings are consistent with polymyositis.

Friday, November 2, 2007

Inflamed eyeball

Today I received a specimen labelled "left eye". It was the eyeball of a 57-year-old gentleman who had sustained trauma to that eye several months ago. The eye was blind and painful, so enucleation was performed. Grossly, there wasn't much to report other than opacity in about half of the cornea. Microscopically, I saw acute and chronic inflammation in the cornea, iris and ciliary body. There also appeared to be mild optic nerve atrophy. The changes were far too acute to allow time for the development of a cyclitic membrane.

Thursday, November 1, 2007

The Cyclitic Membrane

In examining chronically inflamed eyeball specimens, the presence of a cyclitic membrane is not infrequently noted. A cyclitic membrane is connective tissue that extends across the eye from one aspect of the ciliary body to the other. In 1937, Dr. Harvey D. Lamb of St. Louis wrote an article entitled "The Genesis of the Cyclitic Membrane" in the Transcripts of the American Ophthalmologic Society. In it, he explains that "the essential factor in the formation of the cyclitic membrne is the conversion of the macrophage into a connective-tissue cell or fibroblast." He states that since the native fibroblasts of the ciliary body are fixed tissue cells, it "is not possible for them to proliferate through the unbroken pigmented and unpigmented ciliary epithelia". He made these claims on purely morphological grounds (hey, what do you want? it was 1937 after all). However, he does cite in vitro findings wherein cultures of macrophages underwent differentiation and yielded colonies of fibroblasts. In any case, the formation of a cyclitic membrane in chronically inflamed eyes is an interesting phenomenon and one which, when seen in enucleation specimens, I mention as part of my histologic description.

Neuropathology Blog is Signing Off

Neuropathology Blog has run its course. It's been a fantastic experience authoring this blog over many years. The blog has been a source...