PIG PIN

A few weeks ago, I reported on a cluster of atypical inflammatory neuropathy cases among workers at pig processing plants in the midwest.

My colleague, the esteemed Dr. David Stahl, emailed me a link which describes a break in the case.

CNN reports that authorities have figured out how to contain the disease, which they have dubbed Progressive Inflamatory Neuropathy (PIN). They think its an autoimmune phenomenon related to exposure to aerosolized pig brain tissue. Here's the report from CNN:

http://www.cnn.com/2008/HEALTH/conditions/02/28/medical.mystery/index.html

Dr. Sanjay Gupta, CNN's chief medical correspondent, will report on the issue tonight on Anderson Cooper 360 at 9PM central time.

Idiopathic toe walking

A case studied in our second-year medical school curriculum involves a boy with a tip toe gait. The differential diagnosis includes “idiopathic toe walking”. My lovely wife, Jennifer, thought that this topic might be of interest to our dear readers. Here’s an explanation of what is known about this disorder from the introduction to a 2006 paper from Hemo et al in the Journal of Pediatric Orthopedics:

“Persistent tiptoe gait after the age of 2 years in children without discernible neurological or orthopedic abnormality is termed "idiopathic toe walking" (ITW). This diagnosis is made after other disease processes have been excluded. The most common cause of toe walking in childhood is cerebral palsy; however, the differential diagnosis of toe walking includes conditions such as muscular dystrophies, tethered cord syndrome, diastematomyelia, and other neuromuscular diseases. Typically, patients with ITW commence this toe-to-toe gait at the initiation of walking, which occurs at a normal age. There is a positive family history in about 30% of cases.
If left untreated, this pattern of gait has a tendency to persist, and although initially, there is full passive dorsiflexion, an equinus contracture develops with time.”

By the way, according to MediLexicon.com “diastematomyelia” is defined as “complete or incomplete sagittal division of the spinal cord by an osseous or fibrocartilaginous septum.”

Full reference: Hemo Y. Macdessi SJ. Pierce RA. Aiona MD. Sussman MD. Outcome of patients after Achilles tendon lengthening for treatment of idiopathic toe walking. [Journal Article] Journal of Pediatric Orthopedics. 26(3):336-40, 2006 May-Jun.

No need for non-necrotic fiber inflammatory invasion for diagnosis of polymyositis

In the February 5, 2008 issue of Neurology (“The Green Journal”, link below), Nizar Chahin and Andrew Engel of the Mayo Clinic reported on a study of the correlation between muscle biopsy results, clinical course, and outcome in polymyositis (PM) and sporadic inclusion body myositis (IBM). The authors looked at the records of 107 patients with biopsy-diagnosed PM or IBM. The most common diagnosis in this group was IBM (64 patients). The remainder (43 patients) had PM on biopsy, but 16 of those had a clinical presentation that would suggest IBM (this last subgroup are designated as PM/IBM patients).

Non-necrotic fiber invasion by mononuclear cells appeared in all IBM cases, 17 of 27 PM, and 13 of 16 PM/IBM. So only 30 of 43 patients with a pathologic diagnosis of PM actually had non-necrotic fiber invasion by mononuclear cells. That begs the question of what histologic criteria were used to diagnose the other 13 patients with PM when mononuclear fiber invasion was absent?

Well, I emailed this question to one of the authors, Andrew Engel, who was kind enough to promptly reply. He writes that the pathologic criteria for PM used in this study was the presence of an inflammatory exudate present in endomysium, and the absence of features of dermatomyositis, necrotizing vasculitis, muscular dystrophy, or overlap syndromes with myositis but without endomysial inflammation. “In other words,” he writes, “we do not consider invasion of nonnecrotic fibers by cytotoxic T cells and macrophages a necessary criterion for the diagnosis of PM.”

The authors conclude that “although the muscle biopsy is not infallible for the diagnosis of IBM, it remains important for excluding other possible diagnoses, such as distal muscular dystrophies, myofibrillar myopathies, and neurogenic disorders.”

The Ice Pick Lobotomy

My wife, Jennifer, and I recently watched a PBS documentary called “The Lobotomist”, which explores the background of the procedure popularization during the 1940’s through the ‘60’s of the prefrontal lobotomy. The neurologist Walter J. Freeman of Washington, DC was primarily responsible for the widespread performance of this surgery in the United States by developing the 10-minute, outpatient “ice pick lobotomy”. Quite literally, an ice pick was inserted beneath the eyelid and over the eyeball of a patient who was rendered temporarily unconscious by electroshock. When the instrument hit the thin orbital plate of the frontal bone, a few taps with a mallet would allow entrance into the intracranial cavity. The ice pick was then advanced upward, after which it was swept back and forth like a windshield wiper blade. The instrument was then extracted and the procedure was repeated on the opposite side. Approximately 30,000 of these procedures were performed before the medical establishment decided that it was ill-advised.

These procedures were designed to sever the connections of the brain with the prefrontal cortex (the anterior-most portion of the frontal lobes, not including the motor and premotor gyri, which does not cause movements when stimulated by electodes). Patients were left with varying degrees of abulia, but with no motor deficits.

The mechanism of post-traumatic cerebral fat emboli

I was giving a lecture on the pathology of cerebrovascular disease today, and showed a picture from Robbins of a brain with a shower of fat emboli after fracture of long bones. A student asked what the mechanism would be, pointing out that it would be difficult for marrow fat to get from the venous system of the leg into the arterial circulation of the brain without going through the filter of the pulmonary capillary bed.

The etiology of fat emboli after trauma is not clear. According to an article by Butteriss et al. in the American Journal of Neuroradiology, microemboli may pass into the systemic circulation either via cardiac or intrapulmonary right-left shunts or directly through the pulmonary capillary bed. Apparently a study of orthopedic surgery in dogs has shown that fat globules of <5 µm can traverse the pulmonary micovasculature. One could imagine these globules coalescing in the brain and causing significant infarcts, I suppose.

Whatever the mechanism, I imagine air emboli introduced when inserting or pulling out a central line might form in a similar manner.

(Source: D.J.A. Butteriss et al., Reversible Cytotoxic Cerebral Edema in Cerebral Fat Embolism . American Journal of Neuroradiology 27:620-623, March 2006.)

Woody's Dance

Huntington Chorea is a neurodegenerative disease wherein the patient exhibits, among other symptoms, uncontrollable writhing movements known as chorea. This word, chorea, is from the Greek choreía, meaning 'dance'. Probably the most famous person ever to have suffered from Huntington disease is the folk singer Woody Guthrie. Because this is an autosomal dominant disease, there was concern that Woody's folk singing son, Arlo, would also develop symptoms. Luckily, Arlo has now lived 60 years and appears to have been spared. But two of Woody's other children were striken with the disease. A fantastic music blog by Dr. Doug Shevlin, called Music is My Savior, discusses Woody Guthrie's work and a project to put to music previously unknown lyrics written by Woody. Here's the link: http://web.mac.com/scoutmd/Scoutmd/Blog/Entries/2008/2/13_Remember_The_Mountain_Bed.html

The Capgras Delusion in Dementia with Lewy Bodies

Southern Illinois University medical students Sameer Vohra and Teschlyn Woods were discussing Dementia with Lewy Bodies today and mentioned that Capgras syndrome can sometimes be a manifestation of this particular type of dementia. I had never heard of Capgras syndrome, but they explained it to me. Here’s what Wikipedia has to say about it:

"The Capgras delusion (or Capgras's syndrome) is a rare disorder in which a person holds a delusional belief that an acquaintance, usually a spouse or other close family member, has been replaced by an identical looking imposter.... It can occur in acute, transient, or chronic forms.
The delusion is most common in patients diagnosed with schizophrenia, although it can occur in a number of conditions including after brain injury and dementia. Although the Capgras delusion is commonly called a syndrome, because it can occur as part of, or alongside, various other disorders and conditions, some researchers have argued that it should be considered as a symptom, rather than a syndrome or classification in its own right."

It is named after Joseph Capgras (1873-1950), a French psychiatrist who first described the disorder in a 1923 paper by Capgras and Reboul-Lachaux. Here’s the link to the Wikipedia site describing the Capgras delusion:
http://en.wikipedia.org/wiki/Capgras_delusion

CSF outflow isn't only through the arachnoid granulations

We teach our medical students that CSF outflow is through the arachnoid granulations into the venous sinuses. That's true, and good enough for a second year medical school curriculum. But we should keep in mind that some CSF appears to be absorbed by the ependymal lining of the ventricles, as well as in the spinal subarachnoid space and through the walls of the capillaries in the pia mater. Additionally, to quote my source on all of this (Clinically Oriented Anatomy, 2nd edition, by Keith Moore), "some CSF is probably absorbed into the lymphatics adjacent to the subarachnoid space around cerebrospinal nerves (e.g., the optic nerves)."

MGMT and MGMT promoter hypermethylation testing not ready for prime time

A few months ago, an oncologist at my institution asked for an MGMT promoter hypermethylation assay on a high grade glioma. I looked into the issue, and discovered that testing is not standardized yet and really not ready for clinical use. In a review article on molecular testing of gliomas in the January '08 issue of Journal of Neuropathology and Experimental Neurology, the authors concur with this position. That being said, if anyone does want to do immunohistochemistry (IHC) for MGMT, Dr. Roger McLendon at Duke performs this test. Some would argue that PCR is better than IHC, but the good Dr. McLendon counters that immunohistochemistry is more reliable as it correlates with enzyme activity while the PCR promoter methylation assay does not. In any case, I got the oncologist to cancel her request for MGMT promoter methylation studies.