A 69 y.o. woman with diabetes and hypertension presents with rapidly progressive dementia over 4-6 months.

Her MRI is shown below

There is marked cerebral volume loss

Hint: she has no evidence of a stroke and FLAIR signal in several cortical regions

Our patient had Creutzfeldt-Jacob disease proven by a positive 14-3-3 CSF assay and Positive RT-QuIC in the CSF.

Creutzfeldt Jacob disease was first described in the 1920s by German neurologists Hans Gerhard Creutzfeldt and Alfons Maria Jakob.  It is similar to Kuru which is also a prion disease found in people from New Guinea who eat the brains of dead people. Prions are infectious misfolded proteins that can infect nerve cells. They contain no DNA or RNA.   They are responsible for disease in animals like bovine spongiform encephalopathy(mad cow disease), variant Creuztfeld Jacob disease which can be transmitted to humans from animals,  scrapie in sheep and chronic wasting disease in deer, elk, moose and reindeer.

chronic wasting disease is a prion disease found in reindeer.

Everyone has DNA coding for a prion protein on Chromosome 20.  This protein is normally on the surface of cells but can misfold into an infectious protein. Prions aggregate extracelularly to form plaques which cause “holes in surrounding tissue resulting in spongy architecture due to vacuole formation.

the disease is called a spongiform encephalopathy

In the novel Cat’s Cradle by Kurt Vonnegut, there is a weapon called ice-nine.   It is a water molecule modified to have a higher melting point than ice and is a solid at room temperature.  If it is thrown into a body an ocean, the entire body of water freezes.  Similarly , prions cause other proteins to misfold spreading rapidly and irreversibly through brain tissue.  In a similar way  other proteins can cause infectious misfolding among proteins.  Amyloid beta  causes Alzheimers and alpha synuclein causes Parkinson’s.

Prion proteins, once misfolded cannot be killed by radiation or heat. They can be transmitted from infected OR instruments.

Priola S. Cell biology of prion infection .  Handb Clin Neurol 2018;153:45-68.  Doi:10.1016/B978-0-444-63945-5.00003-9.  

Colby D, Prushiner S. Prions. Cold Spring harb Perspect Biol 2011 Jan 3(1)a006833. Doi: 10.1101/cshperspect.a006833

Moda F. Protein Misfolding cyclic amplification of infectious prions. Progress in Molecular Diology and Translational Science. 150:361-374. 

Johnson C, Pedersen J, Chappell R, et al. Oral transmissibility of prion disease is enhanced by binding to soil particles.  2017 PLOS Pathogens 3(7)e93.