Best Post of October 2013: New Study Suggests "Glymphatic System" Flushes Brain of Toxins During Sleep

The next in our "Best of the Month Series comes from a post that appeared on October 22, 2013. Since this posting, The New York Times has picked up on this topic. Perhaps they read it here first? In any case, it's a post worth re-posting:

A new study published in the journal Science on Thursday and reported in the Washington Post suggests that a so-called "glymphatic system" seems capable of flushing toxins (including perhaps  beta-amyloid) from brain -- particularly during sleep.“Sleep puts the brain in another state where we clean out all the byproducts of activity during the daytime,” said study author and University of Rochester neurosurgeon Maiken Nedergaard.
(Thanks to avid NP Blog reader and friend, Dr. Doug Shevlin, for alerting me to this significant new finding.)

Treatable Neurological Disorders Misdiagnosed as Creutzfeldt-Jakob Disease

A case of primary CNS angiitis thought to be sCJD

Dr. Mark Cohen and a team of workers at Case Medical Center in Cleveland, Ohio have published an important article in the Annals of Neurology entitled Treatable Neurological Disorders Misdiagnosed as Creutzfeldt-Jakob Disease (Ann Neurol 2011;70:437–444). Why is this article important? Well, because mistaking a survivable, treatable disorder for a fatal, non-treatable disorder is not optimal. Cohen's team reviewed the pathologic diagnoses of 1,106 patients who were referred for potential prion disease to the National Prion Disease Pathology Surveillance Center (NPDPSC) at Case Western Reserve University from 2006 to 2009. About one-third of the cases did not have prion disease, with Alzheimer disease and vascular disease being the most common conditions accounting for dementia. Further, about one-quarter of the non-prion cases had treatable diseases, including immune-mediated disorders, neoplastic disorders such as lymphoma, as well as infectious and metabolic disorders. The immune-mediated disorders included primary angiitis of the CNS, acute disseminated encephalomyelitis, limbic encephalitis, neurosarcoidosis, paraneoplastic cerebellar degeneration, and one case of Wegener granulomatosis. Of note, more than half of patients with a treatable dementia had a positive CSF 14-3-3 protein test, highlighting the danger of relying too heavily on this test in making a diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD). It turns out that the most specific test for distinguishing CJD from other diseases was magnetic resonance imaging. Drs. David Perry and Michael Geschwind, in a review of this study in the September 2011 issue of Nature Reviews Neurology, (Perry, D. C. & Geschwind, M. D. Nat. Rev. Neurol. 2011:7, 479–480) write: "The fact that many of the non-prion diagnoses in the present study were potentially treatable RPDs [rapidly progressive dementias] should prompt thorough diagnostic testing in patients who are suspected of having sCJD, in order to rule out mimics. The use of CSF testing, contrast-enhanced MRI, and autoimmune antibody screening is supported by this study."

Best Post of February 2011 -- Finally, an alternative to 14-3-3 protein in the diagnosis of CJD!

The next in our "Best of the Month" series is from February 2, 2011:

prion protein

Researchers report in an article in Nature Medicine that a new cerebrospinal fluid test, known as real-time quaking-induced conversion (RT-QUIC) assay, appears to be more specific than the problematic 14-3-3 test, which not infrequently gives false-positive results. ('Quaking-induced' refers to in vitro shaking, which helps to accelerate the reaction.) Not only that: it looks as though RT-QUIC may work on serum samples too, opening up the possibility of much earlier diagnosis and more widespread screening of donated blood. This development could truly revolutionize the pre-mortem diagnosis of prion disease! (Thanks to Dr. Doug Shevlin for calling my attention to this article.)

Beta-2 Transferrin: The Tau of Trauma

Jeannie Williams, a laboratory technician at Memorial Hospital in Springfield, IL, posed a question about beta-2 transferrin testing on cerebrospinal fluid (CSF). Because beta-2 transferrin is a normal constituent of CSF, but not of plasma or mucosal secretions, it is useful in determining whether a patient's nose or ear is leaking CSF versus some other fluid. This is important in determining whether an occult skull fracture or defect has opened a potential route of infection into the central nervous system. In addition to the CSF, beta-2 transferrin is present in the occular humors and the inner ear fluid, which could be an alternative source of this protein in trauma cases where the central nervous system is not actually breached.  In the hospital laboratory, beta-2 transferrin can be detected electrophoretically by immunofixation. Thanks for the question, Jeannie!

Sources:
Tietz Clinical Guide to Laboratory Tests, 4th Edition, Alan H.B. Wu (editor), Saunders Elsevier 2006, p. 1063-5.
Molecular Biology of the Cell, 4th Edition, Bruce Alberts, et al. (editors), Garland Science 2002, p. 935.