Abstract Details

Title A Case of Familial Creutzfeldt-Jakob Disease Masquerading as Fatal Insomnia

Topic Infections/AIDS/Prion Disease

Presentation(s) P06 - (-)

Poster/Presentation
Number 194

Objective

Background BACKGROUND: CJD is a rapidly progressive spongiform encephalopathy. The E200K-129M mutation is found in the majority of familial CJD cases. Those who develop familial CJD are asymptomatic for decades and survive less than one year after becoming symptomatic.

Design/Methods DESIGN/METHODS: We report the case of a 46-year-old Caucasian male without family history of dementia who was well until 2 months prior to admission. He had a rapidly progressive dementia, change in personality, hallucinations, jerky limb movements, and inability to sleep. He expired one week after hospital admission.

Results RESULTS: MRI Brain under general anesthesia was essentially nondiagnostic. PET revealed severe bilateral thalamic hypometabolism and mild-moderate diffuse hypometabolism in frontal, parietal, and temporal lobes as well as in the cerebellum. CSF was negative for 14-3-3 and tau. At autopsy, focal neuronal loss and astrocytosis were prominent in the anterior thalamus although spongiform degeneration and prion plaques were generally absent. Immunohistochemistry with an anti-prion protein antibody revealed plaque-like deposits in the cerebellar molecular layer. Western blot of brain tissue confirmed presence of an abnormal protease resistant prion protein, PrP27-30. Genetic testing was positive for the E200K-129M mutation in the PRNP gene.

Conclusions CONCLUSIONS: This is an unusual case of familial CJD with the E200K-129M mutation because of the genotype-phenotype mismatch; the phenotype and pathology were consistent with fatal insomnia, whereas the genetic results were not. This suggests epigenetic factors play a role in disease expression and emphasizes the role of genetic analysis in prionopathies like CJD and fatal insomnia.

Authors/Disclosures
Karin Mente, MD (Louis Stokes Cleveland VA) PRESENTER	Dr. Mente has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Spear Bio. The institution of Dr. Mente has received research support from National Institute on Aging. The institution of Dr. Mente has received research support from Michael J Fox Foundation.
Pravin George, DO (Cleveland Clinic)	Dr. George has nothing to disclose.
Pierluigi Gambetti, MD (Case Western Reserve Univ)	No disclosure on file
Tracy T. Batchelor, MD, MPH (Brigham and Women's Hospital)	Dr. Batchelor has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Up To Date, Inc. An immediate family member of Dr. Batchelor has received publishing royalties from a publication relating to health care. Dr. Batchelor has received publishing royalties from a publication relating to health care.
Erik P. Pioro, MD, DPhil, FAAN (University of British Columbia)	Dr. Pioro has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avanir Pharmaceutical, Inc.. Dr. Pioro has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amylyx Pharmaceuticals. Dr. Pioro has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argenx. Dr. Pioro has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MT Pharma America, Inc.. Dr. Pioro has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for NeuroTherapia, Inc.. Dr. Pioro has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for MT Pharma America, Inc..

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