2017 NPA-05

Clinical History

A 65-year-old man presented with confusion, memory loss, and ataxia. His family noted that the onset of memory loss had become noticeable over the past three months and had become particularly striking in the past week when he was noted to exhibit abnormal “sudden, jerking movements.” There was no history of alcoholism, psychiatric disease, lithium exposure, or heavy metal exposure. A CT scan was normal. A biopsy was obtained.

Tissue Site
Brain

Whole Slide Image

The whole slide image provided is an H&E stain from a brain biopsy.

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Questions

The presence of a perivascular inflammatory infiltrate in the biopsy would rule out which of the following?
1. Acute demyelinating encephalomyelitis
2. Creutzfeldt-Jakob disease
3. Lyme disease
4. Multiple sclerosis
5. Systemic lupus erythematosus
The presence of vacuolation of the white matter would implicate which of the following?
1. Cerebral amyloid angiopathy
2. Chronic traumatic encephalopathy
3. Parkinson disease
4. Progressive supranuclear palsy
5. Processing artifact
In contrast to other dementing diseases, which anatomic site is typically spared in Creutzfeldt-Jakob disease?
1. Caudate nucleus
2. Cerebellum
3. Frontal Lobe
4. Hippocampus
5. Thalamus

View Answer Key

Discussion and Diagnosis

The diagnosis is Creutzfeldt-Jakob disease (CJD), a spongiform encephalopathy…

Image A: H&E stain, low magnification.

Image B: H&E stain, intermediate magnification.

Image C: H&E stain, high magnification.

Prion protein (PrPc) is a normal protein (the superscripted ‘c’ refers to ‘cellular’) derived from the human prion protein gene (PRNP)…

Image D: IHC. Human prion protein or PrP (3F4) after proteinase K pretreatment.

Electroencephalographic (EEG) studies that exhibit characteristic periodic triphasic complexes at about one per second can be found in the majority of cases, and MRI findings of T2-hyperintensity in basal ganglia and thalami with persistent restricted diffusion on diffusion-weighted imaging (DWI) have been incorporated into the diagnostic criteria for sporadic CJD. Combined with an appropriate clinical examination and cerebrospinal fluid studies demonstrating elevated 14-3-3 protein level, the diagnosis is typically made without a biopsy. However, in certain cases, the disease can be suspected in the absence of typical findings. In such cases, special handling of the brain sample is strongly urged to avoid contamination of laboratory instruments, surfaces, and personnel. The CDC has published guidelines on the proper handling of these samples and familiarity with the guidelines is essential prior to handling a specimen suspicious for CJD. The National Prion Disease Pathology Surveillance Center provides up-to-date information on the handling and submission of tissues to their facility for diagnostic testing.

Diagnosis

Take Home Points

Creutzfeldt-Jakob disease (CJD) is designated as a spongiform encephalopathy by virtue of the pattern of spongy vacuolization observed in gray matter tissue samples under the microscope.
While prion protein is normally found in the human brain, CJD is related to an abnormal accumulation of a misfolded prion protein isoform.
Biopsies and autopsies for the diagnosis of CJD should only be undertaken with precautions in place to prevent contamination.
Biopsy and autopsy tissue should be sent to the National Prion Diseases Pathology Surveillance Center for complete analysis.

References

Goedert M. Neurodegeneration. Alzheimer’s and Parkinson’s diseases: The prion concept in relation to assembled Aβ, tau, and α-synuclein. Science. 2015;349(6248):1255555. doi: 10.1126/science.1255555.
Head MW, et al. Prion Diseases. In: S. Love, et al eds. Greenfield’s Neuropathology. 9th ed. RC Press: Taylor and Francis Group; 2015: 1016-86.
Minikel EV, et al. Quantifying prion disease penetrance using large population control cohorts. Sci Transl Med. 2016;8(322):322ra9. doi: 10.1126/scitranslmed.aad5169.
Peng B, et al. Clinical, histopathological and genetic studies in a case of fatal familial insomnia with review of the literature. Int J Clin Exp Pathol. 2015;8(9):10171-7.
Tousseyn T, et al. Prion disease induces Alzheimer disease-like neuropathologic changes. J Neuropathol Exp Neurol. 2015;74(9):873-88.
Vacca VM Jr. CJD: Understanding Creutzfeldt-Jakob disease. Nursing. 2016;46(3):36-42.

Answer Key

The presence of a perivascular inflammatory infiltrate in the biopsy would rule out which of the following?
- B. Creutzfeldt-Jakob disease
The presence of vacuolation of the white matter would implicate which of the following?
- E. Processing artifact
In contrast to other dementing diseases, which anatomic site is typically spared in Creutzfeldt-Jakob disease?
- D. Hippocampus