2026 American Academy of Neurology Abstract Website

Objective:

We present two cases of sporadic CJD highlighting various ongoing diagnostic challenges.

Background:

Creutzfeldt-Jakob Disease (CJD) is a rare fatal neurodegenerative disorder caused by abnormally folded proteins called prions. It presents with rapidly progressive dementia and a variety of neuropsychiatric features. Diagnosis is challenging given its rarity, overlap with other neurodegenerative conditions, and hesitancy in diagnosing CJD, given its terminal progression with no disease modifying treatment.

Design/Methods:

Retrospective chart review

Results:

Case 1: A 54-year-old woman presented with imbalance, fluctuating expressive aphasia, and fatigue. Initial evaluation suggested vertigo or autoimmune encephalitis given family history of lupus and positive thyroid antibodies. MRI later revealed cortical ribboning and caudate hyperintensities, as well as CSF analysis demonstrated elevated tau and 14-3-3 proteins with a positive RT-QuIC, confirming a CJD diagnosis.

Case 2: A 49-year-old man developed rapid cognitive decline, insomnia, vision changes, and weight loss. Concern for malignancy led to extensive imaging, including PET-CT which was unrevealing. MRI obtained showed questionable cortical diffusion changes and mild global parenchymal loss. CJD diagnosis was confirmed with CSF analysis demonstrating a positive RT-QuIC.

In both cases, patients met criteria for probable CJD diagnosis under current CDC criteria prior to confirmatory RT-QuIC results; however, diagnostic delays stemmed from confounding features in both cases: autoimmune risk factors in Case 1 and concern for malignancy in Case 2. Furthermore, MRI findings in Case 2 were not consistent with classic CJD findings of cortical ribboning and caudate and putamen hyperintensities.

Conclusions:

Through the use of MRI with diffusion weighting and CSF biomarkers with rapid turnaround, a high diagnostic yield can be achieved while awaiting RT-QuIC for CJD confirmation. Applying CDC criteria for probable CJD allows earlier CJD recognition and enables clinicians to begin conversations surrounding diagnosis, palliative care, and advanced care planning aligning with patient treatment goals in the absence of disease modifying therapies.