To identify the clinical features and common tests that distinguish patients with Creutzfeldt-Jakob disease (CJD) from those with “probable CJD” attributed to an alternate cause (i.e., CJD Mimics).

Real-Time Quaking-Induced Conversion assays (RT-QuIC) capable of detecting prions in CSF have greatly improved the antemortem diagnosis of CJD. However, these tests take time to conduct and are not widely accessible. There is a need to leverage clinical features and the results of accessible tests to distinguish patients with CJD from mimics, including patients with potentially treatable causes.

Mimics (11/155; 7%) were diagnosed with autoimmune encephalitis (n=6), neurosarcoidosis, frontotemporal lobar degeneration with motor neuron disease, AV fistula, cerebral amyloid angiopathy associated with inflammation, and polypharmacy. Age-at-symptom onset, gender, presenting symptoms, and EEG and MRI findings were similar between CJD patients and mimics. Focal motor abnormalities (49/93, 11/11), elevations in CSF leukocytosis >5 cells/hpf (4/92, 5/11) and protein >45 mg/dL (39/92, 10/11) were more common in mimics (all p<0.01). Positive RT-QuIC (77/80, 0/9), total-tau levels >1150 pg/mL (75/83, 2/10) and ‘positive’ 14-3-3 (74/91, 4/11) were more common in CJD patients (all p<0.01). Neural-specific autoantibodies associated with autoimmune encephalitis were detected within the serum (4/9) and CSF (6/10) of mimics; and serum of 9/71 CJD cases (not in CSF; all p<0.01).

Autoimmune encephalitis, neurosarcoidosis and neurodegenerative diseases may mimic CJD at presentation and should be considered in patients with early motor dysfunction and abnormal CSF studies.