Human Anatomy at Colby

Grand Rounds: Creutzfeldt-Jakob Disease – An 80-Year-Old Man with Fatigue, Unsteady Gait, and Confusion

January 29th, 2014 · Comments Off on Grand Rounds: Creutzfeldt-Jakob Disease – An 80-Year-Old Man with Fatigue, Unsteady Gait, and Confusion

By: Kasey Kirschner, Jenna Passaggio, Phoebe Hughes

Four weeks before admission an eighty year old man presented with fatigue, insomnia, confusion, and difficulty walking. These symptoms may seem normal for elderly, but they were very uncharacteristic for him.  As his symptoms worsened, he was admitted to the hospital.  However, all tests conducted showed normal results. The test for 14-3-3 protein, which could indicate Creutzfeldt-Jakob, came back negative.  An MRI showed loss of brain volume and changes in his white matter. He was given multiple drugs for insomnia, and he was released three days later.  Cognitive abilities continued to decline, and he began experiencing tremors in his left arm and leg.  He was readmitted to the hospital fifteen days later. Though many tests were done, all returned normal. Nevertheless, his symptoms continued to worsen, and he died after twenty third day of readmission.

The diagnosis was sporadic Creutzfeldt-Jakob disease with MM1. This diagnosis is most likely because of the rapid progression of the patient’s myoclonic jerking and dementia. Additionally, the patient presented with multiple symptoms consistent with other patients diagnosed with Creutzfeldt-Jakobs, including confusion, insomnia, and cerebral ataxia. Despite this, other tests which may indicate Creutzfeldt-Jakobs, such as an MRI or tests for the 14-3-3 protein did not confirm the diagnosis. Upon autopsy, a loss of neurons on the thalamus and spongiform changes of the cerebral cortex were found. This, combined with other symptoms, is indicative of sporadic Creutzfeldt-Jakob disease. However, the patient’s visit to England may suggest the variant form of Creutzfeldt-Jakobs. Only the brain was autopsied, and no other tissues were searched for presence of the PrPSc protein. The PRNP gene was sequenced and showed no mutations, which ruled out familial Creutzfeldt-Jakob disease.  Ultimately, the final diagnosis was sporadic Creutzfeldt-Jakob disease.

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Creutzfeldt-Jakob is hard to diagnose because there is no single test to confirm it, and the tests available can sometimes be misleading.  There are a few which may help indicate the disease such as MRI’s, tests of the cerebrospinal fluid, and EEG’s. The presence of the 14-3-3 protein in the cerebrospinal fluid, high signal intensity on an MRI of T2 weighted images in the basal ganglia, or triphasic spikes on EEG can signify Creutzfeldt-Jakobs. In this case study, none of these tests showed signs of the disease.  An autopsy of the brain and spinal cord may be done to see spongiform changes and neuronal loss.

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Creutzfeldt-Jakob disease is a rare disease affecting approximately one in a million people. It is caused by an infectious prion misfolding. This prion in its active state causes other proteins to misfold as well.  Prions are resistant to proteinase K, which breaks down proteins.  This makes them hard to destroy.  It can be transmitted through transfusions or transplants.  However, the sporadic form of Creutzfeldt-Jakobs disease causes the prions to misfold and become infectious spontaneously. The accumulation of misfolded prions causes holes in the brain which degenerate the brain matter. The neurodegeneration causes numerous and various problems in the patient.

Although some clinical trials are underway, no cure is currently available.  Various treatments have been tested, and some patients have shown very brief periods of improvement, but nothing is available that stops CJD completely.  This disease is treated by alleviating symptoms of the disease to make the patient more comfortable prior to death.

 

 

References:

1. “Creutzfeldt-Jakob Disease Fact Sheet.” National Institute of Neurological Disorders and Stroke. National Institutes of Health, 31 Dec 2013. Web. 12 Jan 2014. <http://www.ninds.nih.gov/disorders/cjd/detail_cjd.htm>.

2. Richard T. Johnson, M.D., R. Gilberto Gonzalez, M.D., and Matthew P. Frosch, M.D., Ph.D. Case 27-2005 — An 80-Year-Old Man with Fatigue, Unsteady Gait, and Confusion. N Engl J Med 2005; 353:1042-1050.September 8, 2005.DOI: 10.1056/NEJMcpc059024

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