Wednesday, February 10, 2016

Did King Henry VIII suffer from chronic traumatic encephalopathy?

Thanks to Dr. Doug Shevlin for alerting me to the following article recently posted on

Henry VIII may have suffered repeated traumatic brain injuries similar to those experienced by football players and others who receive repeated blows to the head, according to research by a Yale University expert in cognitive neurology.

"It is intriguing to think that modern European history may have changed forever because of a blow to the head," said Arash Salardini, behavioral neurologist, co-director of the Yale Memory Clinic and senior author of the study.
Traumatic  explains the memory problems, explosive anger, inability to control impulses, headaches, insomnia—and maybe even impotence—that afflicted Henry during the decade before his death in 1547, according to a paper published online the week of Feb. 1.
The English monarch is best known for his dispute with the Catholic Church over his desire to annul his first marriage to Catherine of Aragon and marry Ann Boleyn. The affair led to the English Reformation and the creation of the Church of England. Henry would marry six times—and execute two of his wives.
Research assistants Muhammad Qaiser Ikram and Fazle Hakim Saijad analyzed volumes of Henry's letters and other historical sources to document his known medical history and events that may have contributed to his ailments. Their findings confirm conjecture by some historians that jousting injuries caused later health and behavioral problems.
Henry suffered two major head injuries during his 30s. In 1524, a lance penetrated the visor of his helmet during a jousting tournament and dazed him. A year later, he was knocked out when he fell head-first into a brook he was trying to vault across with a pole. However, said the researchers, the English monarch's increasingly unpredictable behavior may have been triggered by an accident during a jousting match in January of 1536 when a horse fell on Henry, causing him to lose consciousness for two hours.
"Historians agree his behavior changed after 1536,'' said Salardini, noting that descriptions of Henry during his youth portrayed an intelligent and even-tempered young man who made wise military and policy decisions. His behavior in the later years of his life became notoriously erratic: He was forgetful and prone to rages and impulsive decisions.
In 1546, for instance, he was assuring his sixth wife Catherine Parr, that he would not send her to the Tower of London when soldiers arrived to arrest her. He launched into a tirade against the soldiers, having forgotten that he had given that order the day before.
Other occasional side effects of  are growth hormone deficiency and hypogonadism, which may lead to metabolic syndrome and impotence, respectively. Despite the womanizing reputation of his youth, Henry had difficulty completing sexual intercourse as far back as his marriage to his second wife, Ann Boleyn, in 1533, some evidence suggests.
Other ailments attributed to Henry—such as syphilis, diabetes, or Cushing Syndrome, a condition marked by weight gain and obesity—seem less likely in light of the available evidence, said the study's authors, noting that traumatic brain injury best explains most of his behavioral abnormalities.

Tuesday, February 9, 2016

Best Post of October 2015: Chromothripsis!

The next in our "Best of the Month" series comes from October 1, 2015:
The next edition of the World Health Organization Classification of Tumors of the Central Nervous System will feature a new, separate ependymoma subtype: RELA fusion-positive ependymoma. RELA fusion refers to the juxtaposition of the RELA gene (the principle effector of NF-кB signaling which controls DNA transcription and cell survival) to the poorly characterized C11orf95gene. Fusion of these two genes is brought about by chromothripsis, a term first coined in 2011 that literally means "chromosome shattering". Chromothripsis occurs when chromosomal segments first fragment into many pieces and then get stitched back together in random order by DNA repair processes. Seen in the setting of some malignancies, chromothripsis in a particular segment of chromosome 11 can result in C11orf95-RELA fusion, which in turn drives oncogenic NF-кB signaling in ependymoma.

Chromothripsis (literally meaning "chromosomal shattering") can drive oncogenesis

Although chromothripsis is a novel model for oncogenesis, it does not necessarily contradict more established models of progressive cancer development as there is no definitive proof that chromothripsis has to occur as a single catastrophic event. Nevertheless, this is a fascinating area of research which will undoubtedly yield more insights into the progression of at least a subset of cancers.

Thursday, February 4, 2016

Best Post of September 2015 -- Guest Post: How to make your own Mercado Brain Cutting Device

The next in our Best of the Month Series comes from September 22, 2015:

Today I am fortunate to host a guest blogger, Dr. Juan Mercado, who is a neuropathology fellow at the University of Alabama at Birmingham under the guidance of Drs. Robert Hackney and Kenneth FallonDr. Mercado studied music from a young age and went to a specialized school of music in San Juan, Puerto Rico; but during college he decided to exchange music for medicine and attend the University of Puerto Rico School of Medicine. He has not, however, abandoned his creative approach to the subject matter at hand; in this case, cutting autopsy brains. His guest post follows:

Juan J. Mercado, MD (neuropathology fellow at UAB 2015-17)

A while ago, as a pathology resident, I was temporarily in charge of organizing the weekly brain cutting activity. During this event I always felt a little bothered by the unpredictability and irregularity that occurred with each cut and the variability of results with each different person trying to pursue the same goal.  I decided to do some research trying to find more information about how braingrossing examination was done in different places. To my amazement, I found out about a brain tissue bank in the United Kingdom that performed their coronal sections with the help of a tool. This tool enabled them to create perfect fine cuts every time to perform a complete meticulous evaluation. After knowing about this, I was highly motivated to perform a DIY project. As I optimistically anticipated, the results were excellent. I made the tool using materials that I could easily find in any hardware store. This new and improved tool could now be made by anyone interested in having the same results.  
·        White durable cutting board: the bigger the better (Fig. 1)
Figure 1

·        Straight cabinet handles: they come in different diameters, meaning a different brain slice thickness can be created depending on this diameter. Also they come in different lengths. Choose a length proportionate to the size of the cutting board you select. These bars always come with the screws included. (Fig. 2)
Figure 2

·        Drill: to make four holes 

·        Rubber O-ring washers: not necessary, but I use them just for the preservation of the tool, preventing liquids or tissue to enter in the drilled holes (Fig. 3)
Figure 3

·        Rubber chair legs (to elevate the board from a surface and to hold its placement) (Fig. 4)
Figure 4

With the above materials you can create the basic version that will permit you to create cuts of only one predetermined thickness based on the diameter of the bar you select. You can also have an add-on to be able to do thinner cuts with the same board, but it is not necessary

How it works:
After detaching the brainstem via an axial cut through the midbrain and then making the first brain coronal section cut through the middle of the mammillary bodies, proceed as usual making coronal sections but with the help of the tool
The bars aligned in the way pictured (Fig. 5) serve to hold in place any brain size firmly while cutting. Use a rigid knife sliding it above the bars as a guide. In this way the thickness of the brain sections will be the same as the diameter of the bars 

Figure 5


·        Always the same results, not relying on the experience of the person cutting the brain -- meaning standardization.
·        Homogeneous leveled slices. Option of creating thin slices help in a more meticulous evaluation.
·        When a pathologic finding is present, such as a big intraparenchymal hemorrhage that normally disintegrates the brain slice if performed by normal technique; it does not happen with this tool.
·        Better pictures.
·        It is a lot faster and the cuts are perfect. Less time cutting, more learning and teaching.

See for yourself…

        Add-on(s): Optional (need a saw)
A thinner cutting board cut to fit within the two bars. The diameter of the bar minus the thickness of this board will be your new brain slice thickness, making the same board practical for two different thicknesses.

Thanks, Dr. Mercado. I have often thought about how nice it would be to have a tool that could simplify and standardize braincutting. I am hoping he builds a limited-edition series of these devices and sells them at the next AANP meeting. Since I am not particularly mechanically inclined, I would be the first in line to purchase what I am hereby dubbing "The Mercado Brain Cutting Device"!

Wednesday, January 27, 2016

New chair of University of Louisville Department of Pathology is also the new chair of the CAP Neuropathology Committee

Drs. Dan Brat (left) and Eyas Hattab (right)
The College of American Pathologists' Neuropathology Committee has a new chair: Dr. Eyas Hattab. He replaces Dr. Dan Brat in that role. Dr. Hattab also has recently been named chair of the department of pathology at the University of Louisville. He'll be a great asset to both the CAP and the University of Louisville in his new leadership roles. Best of luck, Eyas!!

Tuesday, January 12, 2016

Guest Post by Mark Cohen and Jeffrey Negrey: Assistance needed for national prion surveillance!

An important request from Dr. Mark Cohen and Jeff Negrey on behalf of the National Prion Disease Pathology Surveillance Center (NPDPSC):

The NPDPSC serves the United States as the national testing site and repository for tissue samples from suspected cases of prion disease (CJD and others). We accept any autopsy tissues for free-of-charge prion testing. With proper tissue procurement, we are able to diagnose with certainty whether or not prion disease is present; and if so, exactly which form and subtype of prion disease (sporadic vs. familial vs. variant) the patient has. Tissue samples are then stored indefinitely and shared with qualified researchers and institutions around the globe.

In order to provide accurate surveillance of prion diseases in the United States, the NPDPSC needs to test CNS tissue. Patients often pass away in non-hospital settings, and even for those who die in hospital, there is ever-increasing reluctance among medical institutions to perform post-mortem examination on patients if CJD is even considered a possibility. Therefore, the NPDPSC offers financial and logistical assistance to families with loved ones suffering from suspected prion disease to obtain a brain-only autopsy and subsequent testing for CJD free of charge to the surviving family (including transportation to-and-from a regional autopsy site if needed). These procedures are coordinated with the nearest approved regional site willing to perform these procedures.

Our national network is a group of public and private autopsy providers located across the country. Sometimes procedures are performed in hospital settings; other times they are performed in mortuary settings prior to final arrangements. We are always looking to add autopsy and mortuary professionals to our network. We encourage all hospitals and medical centers to send us tissue samples from possible prion disease cases as part of our mission to identify and contain potential outbreaks of prion disease. However, we also are willing to reimburse individuals or institutions who accept brain autopsy requests on our behalf. We arrange transport of the patient to a pre-designated autopsy site and provide free-of-charge shipping materials for sending tissue.

If you, or someone you know, would like to join our national network of autopsy providers, please contact Jeff Negrey for further information (phone 216-368-1290 or email

Monday, January 11, 2016

Best Post of August 2015: College of American Pathologists Neuropathology Committee meets

The next in our "Best of the Month" series is from August 15, 2015:

I am delighted to be in Chicago this weekend meeting with my wonderful colleagues on the College of American Pathologists Neuropathology (CAP-NP) Committee. We are making plans for a SAM-eligible educational product that will update you on the 2015 iteration of the World Health Organization Classification of Tumors of the Central Nervous System. The new WHO book is set to be published in October of this year; and we on the committee are making plans to create a CD to be issued a year from now designed to keep you in the loop regarding the latest in CNS tumor classification. This weekend's meeting also marks the end of Dr. Dan Brat's tenure as CAP-NP chairman. Dr. Brat will  be replaced by the illustrious Dr. Eyas Hattab at the helm of the CAP-NP Committee. After a long day at work today on the CAP-NP educational product, committee members retired to Smith and Wollensky Steakhouse for some well-deserved nourishment before returning to finish up our work tomorrow. In addition to Drs. Brat, Hattab, and myself, current committee members include Drs. Bill Hickey,Joe MaRoger McLendon, Matthew Schneiderjan, Aaron Wagner, Cynthia Welsh, and junior member Matthew Cykowski. (Additional note: the next CAP-NP meeting is just a couple of weeks away when we meet at in Key Largo, Florida.)

Rania Hattab (wife of Dr. Eyas Hattab) and Dr. Joe Ma enjoy a morsel of chocolate cake at tonight's CAP-NP dinner

Outgoing CAP-NP committee members Dr. Dan Brat and Dr. Cynthia Welsh will be sorely missed

Thursday, January 7, 2016

Verocay body in a brachial plexus Schwannoma

Verocay body (nuclei palisading around an anuclear zone)
Jose Juan Verocay (1876-1927) [Figure 1] was a Uruguayan physician who trained and worked for most of his adult life in Europe in the late nineteenth and early twentieth century.
Figure 1
Photograph of Jose Juan Verocay (circa 1915)
He was born on June 16, 1876 in the town of Paysandu in Uruguay to immigrant parents. His father Silvino Verocay, was from the Tirol region in southern Austria and his mother Rosalia Garrone, was from the dolomite region of northern Italy and the family name is possibly derived from the town of Verocai which is near Cortina D’Ampezzo located in the Dolomitic Alps in north-eastern Italy. (From Joshi R., Learning from Eponyms: Jose Verocay and Verocay bodies, Antoni A and B areas, Nils Antoni and Schwannomas. Indian Dermatology Online Journal 2012 Sept-Dec; 3(3): 215-219.)