Big Belly can result in later Alzheimer disease

The revered Dr. Michael Beckman sent me a recently published Associated Press article by Malcom Ritter on research suggesting that “having a big belly in your 40s can boost your risk of getting Alzheimer's disease or other dementia decades later.”
By ‘big belly’ the researchers, headed by Rachel Whitmer of the Kaiser Permanente Division of Research in Oakland, Calif, are not talking simply about weight. Although obesity can increase the risk of later Alzheimer disease, there seems to be “a separate risk from storing a lot of fat in the abdomen” even for people who were not overweight.
This is another example of how traits which predispose to the development of heart disease are also linked to later dementia.

Key excerpts from the article are as follows:
“That abdominal fat, sometimes described as making people apple-shaped rather than pear-shaped, has already been linked to higher risk of developing diabetes, stroke and heart disease.
"Now we can add dementia to that," said study author Rachel Whitmer.
“She and others report the findings in Wednesday's online issue of the journal Neurology.
Analysis found that compared to people in the study with normal body weight and a low belly measurement:
- Participants with normal body weight and high belly measurements were 89 percent more likely to have dementia.
- Overweight people were 82 percent more likely if they had a low belly measurement, but more than twice as likely if they had a high belly measurement.
- Obese people were 81 percent more likely if they had a low belly measurement, but more than three times as likely if they had a high measurement.”

Thanks for the article, Dr. Beckmann.

Featured Neuropathologist: John E. Donahue, MD

Today we feature a rising star in the neuropathology firmament: John E. Donahue, MD. Counted among the prominent neuropathologists on Wikipedia’s neuropathology page (see ‘links of interest’ below), Dr. Donahue is making an impact on the field in terms of teaching, research, and diagnostics. He is co-director of the first-year brain sciences course at Brown Medical School; an authority on blood-brain barrier research in Alzheimer’s disease; and the pre-eminent diagnostic neuropathologist at Rhode Island Hospital in Providence, Rhode Island. Dr. Donahue personifies neuropathology in the 21st century.

The New York Times finds Neuropathologists Worthy

First I'd like to thank the esteemed Adam King (MSII at SIU), a loyal reader, for his comments on my blog entries. Secondly, I'd like to thank Dr. Mark Cohen (Case Western) for reminding me about an article that appeared in the New York Times last year about a neuropathologist. The reporter attended the brain cutting session of Dr. Jeffrey Joseph, then of Beth Israel Hospital of Boston, and assessed the state of neuropathology in modern medical education. It's appropriate that I'm posting this article today since I'll be doing a brain cutting session this morning at 8AM. Here's the link to the NYT article:
http://www.nytimes.com/2007/09/11/health/11prof.html?_r=1&ref=science&oref=slogin

A new disease which lawyers love

Neuropathologists are always reviewing brain MRIs that use gadolinium contrast. I never thought much about the potential toxic effect of gadolinium. However, the illustrious Dr. Brajesh Argawal, resident in the Southern Illinois University School of Medicine neurology program, informed me yesterday of the risk of the use of gadolinium-based MRI contrast agents in patients with chronic renal failure. There is an emerging disorder, known as nephrogenic systemic fibrosis (NSF), that can arise in these patients. NSF involves the deposition of collagen in the skin and other organs in patients either on dialysis or with a glomerular filtration rate of less than 15 cc/min. According to an article on the topic by Philip Kuo et al. in the journal Radiology (2007;242:647-649), “NSF may develop rapidly and can sometimes result in patients becoming confined to a wheelchair within a few weeks… While NSF sometimes stabilizes, it rarely spontaneously remits.” Malpractice lawyers are, of course, all over NSF. For instance:
http://www.mri-contrast-lawsuit.com/

Radiologists now make it a practice to have patients sign a consent form which mentions the possibility of the development of NSF in those with renal insufficiency. Here’s a link to the FDA alert concerning gadolinium:
http://www.hpcbd.com/FDA%20Gadolinium%20Alert.pdf

Thanks for the information, Dr. Argawal!

There’s Pelizaeus-Merzbacher disease, and then there’s Pelizaeus-Merzbacher-like disease

Thanks to the esteemed Dr. Mark Cohen of Case Western Reserve University, who sent me a recently published article entitled: GJA12 mutations are a rare cause of Pelizaeus-Merzbacher-like disease (Henneke M, et al. Neurology 2008;70;748-754). The plain old form of Pelizaeus-Merzbacher disease, the prototypical hypomyelinating leukodystrophy secondary to an inborn error of myelin formation, is caused by a mutation in the proteolipid protein 1 (PLP1) gene on the X chromosome. But Pelizaeus-Merzbacher-like disease differs from the classical form in being associated with a mutation other than PLP1. One genetic substrate of PMLD was first described by Dr. Jutta Gartner’s group in Goettingen, Germany as having an autosomal recessive inheritance pattern associated with mutation in gap junction protein alpha-12 (GJA12). In this study, the Gartner group looked at 193 patients with PMLD and found that only 8.3% of them carried the GJA12 mutation. Finally, the authors write: “The clinical phenotype of patients with a GJA12 mutation was evaluated and is overall comparable to the clinical features seen in mild forms of proteolipid protein 1(PLP1) related disorder but with better cognition and earlier signs of axonal degeneration.” Thanks again for the article, Mark!

Dr. Bob Struble, of SIU School of Medicine, had this to say....

"Your picture just needs a long stem pipe and you would look like a acromegalic leprechan. Is this any way to present the backwater of neuropathology to the rest of the sentient universe?
:-D"
==========================================

The Early Descriptions of Ammon's Horn Sclerosis

A reader requested a post about epilepsy. In searching the internet, I found a nice article by Keiji Sano from Teikyo University School of Medicine in Japan which describes the history of hippocampal epilepsy surgery for Ammon’s horn sclerosis (AHS). Here’s an excerpt from Sano’s article. I should note that when Sano refers to the “endplate” or “end folium”, he is referring to the CA4 region of the hippocampus, which I have now learned can also be referred to as Bratz’s sector:
“The first gross description of AHS is generally credited
to Bouchet and Cazauvieilh, who in 1825 observed
changes of sclerosis or softening in the hippocampus
of epileptic as well as of nonepileptic psychopathic
patients. Sommer performed the first microscopic examination
of AHS in 1880, showing the changes to be
restricted to the band of pyramidal cells of the hippocampus,
which has since been called “Sommer’s sector.”
He also coined the term “Amrnonshornsklerose.”
In 1889, Chaslin described a marginal gliosis in cases
of epilepsy and regarded AHS sclerosis as representing
merely a site of predilection for such gliosis. In 1899,
Bratz confirmed Sommer’s findings but noted that
the endplate or the end folium was as often affected as
Sommer’s sector (and therefore later called Bratz’s sector)
and that a portion of the dorsal cell band was resistant
in many cases. He determined that AHS existed in
25 of 50 cases of idiopathic epilepsy and also noted the
same lesion in other diseases associated with convulsive
disorder.”
Epilepsia, 38(Suppl. 6):4-10, 1997
Lippincott-Raven Publishers, Philadelphia
0 International League Against Epilepsy

Here’s a link to the full article:
http://www.blackwell-synergy.com/action/showPdf?submitPDF=Full+Text+PDF+%28828+KB%29&doi=10.1111%2Fj.1528-1157.1997.tb00098.x&cookieSet=1

Grumose degeneration in the cerebellar dentate nucleus

It’s hard to find a picture of grumose degeneration in a textbook or online. I did, however, find one in an article by Yamanouchi et al. entitled “An Autopsy case of ornithine transcarbamylase deficiency” [Brain & Development 24 (2002) 91-94]. Grumose degeneration appears as eosinophilic granular material around dentate neurons. Neuropathologists usually think of grumose degeneration of the cerebellar dentate as an autopsy finding in progressive supranuclear palsy (PSP). But the authors of this article describe the same finding in a case of ornithine transcarbamylase deficiency, the most common heritable urea cycle disorder. They point out that although grumose degeneration was first described in a patient with PSP, it has also been reported in certain other neurodegenerative disorders, such as dentatorubropallidoluysian atrophy, Ramsay-Hunt syndrome, and juvenile Alzheimer disease with myoclonus. Ultrastructural studies have revealed that this eosinophilic material corresponds to degenerate Purkinje cell axon terminals. By the way, the word ‘grumose’, which can also be spelled ‘grumous’, means granular and refers to something that resembles grume, which is (according to Webster’s online dictionary) a thick, viscid fluid or clot-like material.

John Onians and Neuroarthistory

Shelley Cordulack, professor of art history at Millikin University in Decatur, IL alerted me today to the work of John Onians, originator of the concept of neuroarthistory. Onians is Professor Emeritus at the University of East Anglia. His new book, Neuroarthistory: From Aristotle and Pliny to Boxandall and Zeki, explores the way in which artists think and how thought processes differ between time periods and locations. Thanks, Shelley!

Frontal lobe metastases cause Phinaes Gage syndrome

I got this email from my esteemed colleague and friend, Dr. Gerald Colvin:

"Hi Brian,
Here is an addition to your blog from your esteemed colleague and friend. This patient has metastatic non-small cell lung carcinoma and presented to us with mental status changes. He was found to have bilateral frontal lobe tumors causing significant edema. What is interesting about this case was that he has personality changes reminded me of those of Phineas P. Gage was reported to have. Gage's remains I believe are housed in Boston. I did see something on display in a London museum when I was there a million years ago
Ger-"

Most of us know the story of the railroad construction foreman Phineas Gage, who, in 1848, suffered an accident on the job which resulted in a 13-pound iron rod shooting through the front of his brain. Gage survived the accident, and lived 11 years more. But he was never the same. His physician, Dr. Harlow, describes Phineas some time after the accident as “fitful, irreverent, indulging at times in the grossest profanity (which was not previously his custom), manifesting but little deference for his fellows, impatient of restraint or advice when it conflicts with his desires.” (Reference: Phineas Gage: A Gruesome But True Story About Brain Science by John Fleischman, HMCo Children’s Books, 2004).

Dr. Mark Cohen's second favorite neuro blog

The esteemed Dr. Mark Cohen of Case Western Reserve University sent me a link to what he calls his second favorite neuro blog. Its titled neurophilosophy. Its focus is neuroscience. Neurophilosophy is listed among my permanent links at the bottom of this page. Here's the link:
http://scienceblogs.com/neurophilosophy/

Thanks, Dr. Cohen!