Abstract Details

Title Diagnostic Value of Clinical Phenotype and Clinical Tests in Early Creutzfeldt-Jakob Disease

Topic Infectious Disease

Presentation(s) S38 - All Things HIV and ID (5:18 PM-5:30 PM)

Poster/Presentation
Number 010

Background

The wide spectrum of neurologic and psychiatric symptoms in patients with CJD confounds diagnosis. CJD diagnostic criteria emphasize detection of specific symptoms/signs, and test findings, yet it is unclear when in the disease course these features emerge.

Objective To determine the frequency of clinical symptoms, signs, and supporting findings at initial evaluation for Creutzfeldt-Jakob disease (CJD), and their relationship to disease duration.

Design/Methods Clinical data were extracted from the medical records of patients with probable or definite CJD at Mayo Clinic from 2014-2021. Diagnosis was established by clinical consensus for cases without neuropathological confirmation. Univariate and multivariate statistics were used to evaluate the associations between dominant presentation and demographics, clinical manifestations, laboratory results, electroencephalogram (EEG) findings, neuroimaging findings, and neuropathology.

Results

Our series included 115 patients: 43 (37.4%) definite and 72 (62.6%) probable CJD. The mean age at symptom onset was 64.8 years (±SD 9.4), 68 patients were female (59.1%). The most frequent dominant presentation was cognitive (49 [42.6%]), followed by global (28 [24.3%], involving multiple neurological domains), cerebellar (22 [19.1%]), and motor (12 [10.43%]) presentations. Psychiatric presentations were rare (4 [3.5%]). Myoclonus was present in 27% and related to clinical phenotype (χ2(4, N=115) =18.657, p=0.001). Myoclonus detection was associated with a mean reduction of 186 days in survival (95% CI [35, 336]) controlling for age. Diagnostic tests supportive of CJD at initial assessment included MRI (diffusion-weighted imaging within the basal ganglia, thalamus, or cortex), 76.5% (88/115); EEG (periodic discharges/PLEDS), 16.2% (17/105); CSF (t-tau >1149 pg/mL), 87.5% (63/72), “positive” 14-3-3, 60.0% (54/90), and “positive” RT-QuIC, 91.7% (66/72). Total CSF t-tau levels associated with time-to-death (Pearson’s rho=-0.295, p=0.006).

Conclusions

Symptoms/signs, and findings on supportive tests vary in patients with CJD at initial assessment. The results of multiple tests should be considered to establish a diagnosis of CJD.

Authors/Disclosures
Dror Shir, MD (Mayo Clinic) PRESENTER	Dr. Shir has nothing to disclose.
Evelyn Lazar, MD (JFK Medical Center)	Dr. Lazar has nothing to disclose.
Jonathan Graff-Radford, MD, FAAN	Dr. Graff-Radford has received personal compensation for serving as an employee of Mayo Clinic. Dr. Graff-Radford has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for NINDS/NIH. The institution of Dr. Graff-Radford has received research support from NIH. The institution of Dr. Graff-Radford has received research support from Eisai. The institution of Dr. Graff-Radford has received research support from Cognition therapeutics.
Allen J. Aksamit, Jr., MD, FAAN (Mayo Clinic)	Dr. Aksamit has nothing to disclose.
Jeremy K. Cutsforth-Gregory, MD, FAAN (Mayo Clinic)	Dr. Cutsforth-Gregory has received publishing royalties from a publication relating to health care.
David T. Jones, MD (Mayo Clinic)	Dr. Jones has received intellectual property interests from a discovery or technology relating to health care.
Hugo Botha, MD (Mayo School of Graduate Medical Education, Rochester)	Dr. Botha has received research support from NIH.
Vijay K. Ramanan, MD, PhD (Mayo Clinic)	The institution of Dr. Ramanan has received research support from the National Institutes of Health. The institution of Dr. Ramanan has received research support from the Mangurian Foundation for Lewy Body Disease Research. The institution of Dr. Ramanan has received research support from as part of clinical trials sponsored by the Alzheimer's Association, Eisai, the Alzheimer's Treatment and Research Institute at USC, and Transposon Therapeutics, Inc.. The institution of Dr. Ramanan has received research support from Medscape. Dr. Ramanan has received personal compensation in the range of $500-$4,999 for serving as a Conference Speaker/Organizer (Honoraria) with AANI.
Christian C. Prusinski, DO (Mayo Clinic)	Dr. Prusinski has nothing to disclose.
Amanda L. Porter, MD (Mayo Clinic)	Dr. Porter has nothing to disclose.
Gregory S. Day, MD, MSc, FAAN (Mayo Clinic)	Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Parabon Nanolabs. The institution of Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eli Lilly. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys Therapeutics. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ionis. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for DynaMed (EBSCO Health). Dr. Day has stock in ANI Pharmaceuticals. The institution of Dr. Day has received research support from National Institutes of Health / NIA. The institution of Dr. Day has received research support from Chan Zuckerberg Initiative. The institution of Dr. Day has received research support from Alzheimer's Association. The institution of Dr. Day has received research support from National Institutes of Health / NINDS. The institution of Dr. Day has received research support from Horizon Therapeutics. The institution of Dr. Day has received research support from AVID Radiopharmaceuticals. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Presenter at Annual Meeting (CME) with American Academy of Neurology. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Content Development (CME) with PeerView, Inc. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving as a Content Development (CME) with Continuing Education, Inc. Dr. Day has a non-compensated relationship as a Clinical Director with AntiNMDA Receptor Encephalitis Foundation that is relevant to AAN interests or activities.