Neuropathology

Creutzfeldt-Jakob disease (CJD)

Matthew Frosch
Massachusetts General Hospital
Boston, MA


Clinical History
A 58 y/o right-handed woman initially complained of being in a "brain fog," with fuzzy thinking and difficulty concentrating. She next reported feeling dizzy/off balance and short-term memory loss became apparent to her family and co-workers. She also noted bilateral hand-eye apraxia (e.g., unable to correctly utilize the remote control or microwave). She also began having staring spells where she would have a glassy look in her eye lasting for less than one minute. She additionally had jerking/twitching irregularly, temporally unrelated to the staring spells and without loss of consciousness or changes in her baseline degree of mental status. Her husband reported that she had begun to startle quite easily and that she had occasional visual hallucinations (e.g. telling her husband that he had a cut on his chin when he didn't). He also reported that she had mild word-finding difficulty. She was admitted to the hospital approximately 3 months after the first symptoms.

Her neurologic examination revealed her to be unable to state her name, age, location or history. She mis-stated the date and perseverated with the incorrect answer. She was unable to name the months of the year forward, let alone backward. She had minimal speech production, either spontaneously or in response to questions. She was unable to name objects, read or write but repetition was preserved. She was able to hold a pen but was unable to put it to paper. Cranial nerve exam was unremarkable, although inadequate cooperation prevented testing of I, XI or XII. Motor, sensory and coordination testing were compromised because of poor cooperation, but she showed moderate rigidity in the upper extremities along with myoclonus in all extremities.

Because of a history of lupus, she was treated with 1 gm solumedrol IV x 3 days, without improvement. A lumbar puncture revealed an opening pressure of 12, glucose 67, protein 40, no oligoclonal bands, WBC 3, RBC 30. Cultures of CSF did not grow any organisms and PCR studies for herpes virus were negative. MRI revealed restricted diffusion and subtle T2 hyperintensity along the L >R frontal cortical ribbon, as well as the L striatum. An EEF showed generalized slowing and delta of varying asymmetry over each anterior rolandic regions, but no spikes or slow wave discharges. She was discharged to hospice care and died several days later. An autopsy was performed.

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Figure 1
Diffusion weighted MR images at two levels showing ribbon-like multifocal cortical restricted diffusion as well as restricted diffusion in the striatum.
Figure 2
Cerebral cortex shows mild spongiform change in some areas (LHE stain)
Figure 3
Vacuolization of cerebral cortex shows some degree of clustering (LHE stain)

Figure 4
A mixture of larger and smaller vacuoles can be seen, including some which are evident within neuronal cytoplasm (LHE stain)
Figure 5
Even some of the larger vacuoles are present within neuronal cell bodies (LHE stain)
Figure 6
Involvement of the grey matter of the striatum is in clear contrast to the absence of vacuoles in the pencil fibers of Wilson (LHE stain)

Figure 7
The involvement of cerebellar cortex is mostly observed in the molecular layer, with good preservation of the folial white matter (LHE stain)
Figure 8
The vacuoles progress from small individual lesions to larger more confluent areas.


Differential Diagnosis
1. Creutzfeldt-Jakob disease (CJD)

2. Variant Creutzfeldt-Jakob disease (vCJD)

Final Diagnosis and References
Creutzfeldt-Jakob disease (CJD)

Key words:
prion disease, neurodegenerative disease, dementing illnesses

References
  1. Prusiner SB. Shattuck lecture--neurodegenerative diseases and prions. N Engl J Med. 2001;344:1516-1526.

  2. Collinge J. Molecular neurology of prion disease. J Neurol Neurosurg Psychiatry. 2005;76:906-919.

  3. Parchi P, Giese A, Capellari S, et al. Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects. Ann Neurol. 1999;46:224-233.

  4. Brown P, Wolff A, Gajdusek DC. A simple and effective method for inactivating virus infectivity in formalin-fixed tissue samples from patients with Creutzfeldt-Jakob disease. Neurology. 1990;40:887-890.

  5. WHO Infection Control Guidelines for Transmissible Spongiform Encephalopathies. Geneva: World Health Organization; 2000.

  6. WHO Guidelines on Transmissible Spongiform Encephalopathies in relation to Biological and Pharmaceutical Products. Geneva: World Health Organization; 2003.

  7. Macfarlane RG, Wroe SJ, Collinge J, Yousry TA, Jäger HR. Neuroimaging findings in human prion disease. J Neurol Neurosurg Psychiatry. 2007 Jul;78(7):664-70

  8. Wadsworth JD, Powell C, Beck JA, Joiner S, Linehan JM, Brandner S, Mead S, Collinge J. Molecular diagnosis of human prion disease. Methods Mol Biol. 2008;459:197-227.