Neuropathology Blog takes a holiday

To my dozens of loyal readers out there, I should let you know that I'll not be posting for the next month. William Butler Yeats said that a fulfilled life is one in which there is "a continuous drinking of knowledge". I hate to interrupt the imbibing; but I promise to return with a tall glass of neuropathology on June 30, 2008. In the meantime, may your hippocampi continue to be stimulated elsewhere!

LGMD2B versus Miyoshi myopathy

I asked the good people at the Jain Foundation (https://www.jain-foundation.org/), an organization devoted to the treatment of Limb Girdle Muscular Dystrophy 2B/Miyoshi myopathy, to help me understand the difference between the two diseases. The Jain Foundation’s director of research, Laura Rufibach, PhD, gave the following informative response:

“Limb-girdle muscular dystrophy and Miyoshi Myopathy are general clinical designations that are given depending on the initial pattern of muscle weakness seen in patients. LGMD is characterized by proximal muscle weakness, while Miyoshi Myopathy is characterized by distal muscle weakness.

“There are 19 genetically defined forms of LGMD (6 dominant and 13 recessive). Clinically, many of the LGMDs are similar and the exact form can only be identified by protein screening or the identification of mutations. For LGMD2B, the “2” signifies the recessive nature of the disease and the “B” indicates that the LGMD is caused by a problem with the dysferlin protein.

“Miyoshi Myopathy is also a genetically heterogeneous form of muscular dystrophy with 3 different linked loci identified to date. At present, mutations in only one gene have been identified that are known to result in Miyoshi Myopathy. That gene, like LGMD2B, is dysferlin.

“Therefore, LGMD2B and Miyoshi Myopathy (caused by mutations in dysferlin) are allelic disorders. The initial clinical presentation (i.e. pattern of muscle weakness) of LGMD2B and Miyoshi Myopathy are very distinct. However as the disease progresses, the majority of patients begin to show a mixture of both distal and proximal weakness. Some patients even initially present with a mixture of both proximal and distal muscle weakness. There are even some reports of both an LGMD2B and Miyoshi Myopathy presentation occurring in siblings within the same family with the same genetic mutations.

“Therefore from my perspective as a geneticist, LGMD2B and Miyoshi Myopathy (resulting from mutations in dysferlin) are the same disease and the variations in clinical presentation are the result of other modifiers (genetic or environmental) that have yet to be identified. Given this fact both LGMD2B and Miyoshi Myopathy could be treated with the same genetic therapeutic approaches (i.e. gene therapy, exon skipping, etc). This is why we include both types of patients in our patient registry."

Anatole France had a small head and a Nobel Prize

Dr. David Drachman writes in an editorial in the current Neurology (6 May 2008, p. 1725-7): “Statistically, people with larger brains have higher intelligence, but for individuals the rule is fallible: the Nobel laureate, Anatole France, was known to have an extremely small head.”

Greenfield's has arrived!

It finally arrived in the mail from Amazon.com yesterday: Greenfield’s Neuropathology, 8th Edition (2 Volume Set with DVD). All $599 worth. Because I ordered it before publication, I paid “only” $569.05. Editors Seth Love (Frenchay Hospital, Bristol, UK), David Louis (Mass General Hospital, Boston), and David Ellison (St. Jude Children’s Hospital, Memphis, TN) promise in the preface that in this new edition “all of the chapters are either entirely new or have been revised and updated… This expansion of content is supported by 700 extra figures (the total has increased to just over 2700) and 80 extra tables (an increase to 212).” And the companion DVD contains these figures as well. (Of course, I was just reminded that my PC in the office only has a CD player and so I cannot access the electronic images unless I bring my trusty MacBook to work.)

Kennedy is diagnosed with malignant glioma

Medical student Sameer Vohra informed me that he came to this blog looking for more information on Sen. Ted Kennedy's brain tumor. Also in my email inbox this morning was a link from Dr. Doug Shevlin to an article in the Chicago Tribune about Kennedy's disease. The press is reporting that Kennedy has a "malignant glioma", which of course is an umbrella term that includes diffuse astrocytoma, anaplastic astrocytoma, glioblastoma multiforme, anaplastic oligodendroglioma, oligoastrocytoma, and anaplastic ependymoma. The most likely diagnosis in someone in Kennedy's age group is glioblastoma multiforme (GBM). Unfortunately, the mean survival in patients with GBM is eleven months. Despite treatment, the prognosis for patients wth GBM is dismal. The May 20 Chicago Tribune article forwarded to me by Shevlin notes that Kennedy suffers from chronic pain secondary to a plane crash in 1964 that "broke his back". Our own Senator Dick Durbin (D-IL) said: "Everyone I know just marvels at his strength. Any other person just would have been classified as a disabled person and unable to work after the injuries he sustained. He's never complained, but I've seen the pain on his face. He soldiers on without a word of complaint."

Why do most of us have an interthalamic adhesion?

Neil asks a very good question. What is the difference between those with, and those without, an interthalamic adhesion. I found a 1991 article in Science by Ann Gibbons entitled “The brain as ‘sexual organ’” (Science 30 August 1991: 957-959) which states that the “massa intermedia tends to be absent altogether in men more frequently than it is in women. While the function of the massa intermedia isn't known, some early NIH studies have found a correlation between the presence of it and I.Q. scores (with different patterns in men and women). Says [Sandra J.] Witelson, [a McMaster University behavioral neuroscientist]: ‘Obviously, intelligence isn't situated in the massa intermedia, but it could be correlated with other anatomical features that are relevant to some aspects of intelligence.’”

However, I posed Neil’s question to Dr. George R. Leichnetz, neuroanatomist at Virginia Commonwealth University and author of Digital Neuroanatomy: An Interactive CD Atlas with Text (Wiley-Liss, 2006). Here is Dr Leichnetz’s emailed response to my query:
“The "interthalamic adhesion" or "massa intermedia" is (as its name implies) an adherence of the ependymal lining of the midline third ventricle. Importantly, it is not a commissure, ie. there are no inter-thalamic fibers exchanged between the two thalami. In subhuman primates and other mammals there is a true midline commissure through which fibers are exchanged. But in man the functions of the two cerebral hemispheres are specialized and separate, hence, their principal source of afferents, the thalamus, are separate. It would be functionally disadvantagious if there were a commissure at the level of the thalamus. So, the absence of this adhesion has no negative functional consequence as far as I know.”

The next time I do a brain autopsy, I’ll take a microscopic section of the interthalamic adhesion and post a photomicrograph to prove Dr. Leichnetz’ point. Given Dr. Leichnetz’ comments, it would be highly unlikely that the presence of an interthalamic adhesion would have anything directly to do with intelligence -- or anything else, for that matter!

The interthalamic adhesion is absent in 20% of humans

At this morning's brain cutting conference, the question arose as to whether or not the interthalamic adhesion is present in all humans. According to Dr. Bob Struble's memory, and confirmed by my internet search, the interthalamic adhesion (also known as the massa intermedia) is indeed sometimes not present. According to biology-online.org, the massa intermedia is a "variable connection between the two thalamic masses across the third ventricle; absent in about 20% of human brains." Moreover, in my copy of The Ciba Collection of Medical Illustrations (1991), Dr. Frank Netter implies that more than one adhesion can be present. He writes on page 29: "The medial surfaces are joined by a band (or bands) - the interthalmaic adhesion (massa intermedia)." There you have it. Have a good weekend!

RPD ≠ CJD

The first thing most of us think of when a patient presents with rapidly progressive dementia (RPD) is Creutzfeld-Jakob disease (CJD). But not so fast! Michael Geschwind, with Aissa Haman and Bruce Miller, of the University of California at San Francisco wrote a good review article in Neurologic Clinics [Neurol Clin 25(2007) 783-807] entitled “Rapidly Progressive Dementia”. The authors reviewed the records of 825 patients referred to their institution for RPD, many with a presumptive diagnosis of CJD. Most of the patients ended up with the diagnosis of definite or likely prion disease. But 18% had other diseases, many of which were treatable. The non-prion causes of RPD, in descending order of incidence, included neurodegenerative, autoimmune, other infectious, psychiatric, and miscellaneous disorders. The most common neurodegenerative disorder presenting with RPD appears to be Alzheimer disease, particularly when present in conjunction with amyloid angiopathy.

More News From Nowhere

The good Dr. Doug Shevlin suggested that I relate a story I told to him this morning which has a neuropsychiatric theme. The other night, I was in bed holding my 11-month-old son when I asked my wife to hold the baby. She replied that I must be joking. I answered that I needed her to hold the baby. She replied: "Ah, you're holding my leg." At that point, I awakened to find that I wasn't holding my little boy at all. He was asleep in his crib in the next room. It seems that I had experienced a hypnopompic hallucination, which, according to medicinenet.com is a vivid dreamlike hallucination that occurs as one is waking up. Usually these are auditory and visual in nature, but mine actually had a tactile component to it. In the opposite situation, if one hallucinates as one is falling asleep, it is referred to as a hypnogogic hallucination. Very strange. Dr. Shevlin's blog post today (see Music is My Savior link below) is titled 'More News From Nowhere', which is certainly where I was reporting from during my recent hallucinogenic state!

The Best Post of January, 2008

An installment of my "best post" series:
The best neuropathologyblog post in January of 2008 presented frozen section room rules as described by Dr. Mark Cohen of Case Western in his seminar called "Neuropath@Nite – Staying Cool in the Frozen Room”. The seminar, presented at the annual College of American Pathologists meeting in October of 2007, was conducted in collaboration with Dr. Joe Parisi of the Mayo Clinic.

Here are Frozen Room Rules to live by:
1. You, and you alone, know if you need more tissue to make an intraoperative diagnosis.

2. When misdiagnosing a lesion, always strive to do the least amount of harm!

3. Lipid-laden macrophages are very strong evidence against the presence of a glioma.

4. Rule number 2 trumps rule number 3 (explained as: “It is easier to reoperate on a patient with a glioma initially misdiagnosed as a tumor-like demyelinating lesion, than replace resected demyelinated tissue initially misdiagnosed as gliomas.”)

I'm not the only path-poster in the blogosphere!

One of my favorite pathology blogs is published by Ole Eichhorn, Chief Technical Officer of Aperio Technologies, a digital pathology company in San Diego. Eichhorn’s blog, The Daily Scan (http://blog.aperio.com/), covers news and offers opinions about pathology, technology, and the interface between the two. A related blog, Digital Pathology Blog (www.tissuepathology.typepad.com), addresses issues pertaining to telemedicine and image technology.

Best Post of December '07

This post was an answer to a quiz question posed on the previous day:

From what disease did "the Elephant Man" suffer?

Joseph Merrick was originally thought to be suffering from neurofibromatosis type I, a genetic disorder also known as von Recklinghausen's disease. However, it was postulated in 1986 that Merrick actually suffered from Proteus syndrome (a condition which had been identified by Michael Cohen seven years earlier). Unlike neurofibromatosis, Proteus syndrome (named for the shape-shifting god Proteus) affects tissue other than nerves, and is a sporadic rather than familially transmitted disorder. In July 2003, Dr. Charis Eng announced that as a result of DNA tests on samples of Merrick's hair and bone, she had determined that Merrick certainly suffered Proteus syndrome, and may have had neurofibromatosis type I as well. (The above information is adapted from the wikipedia article. But citations are provided.)

The clinical manifestations of Proteus syndrome are, as the name implies, protean. They include: partial gigantism of hands or feet; hemihypertrophy; subcutaneous lipomas; multiple nevi; areas of thickened skin and subcutaneous tissue; macrocephaly; skull anomalies; and accelerated growth in long bones. Mentation can be normal or retarded.