Prognostic Features of Sporadic Creutzfeldt-Jakob Disease: An Analysis of Taiwan's Nationwide Surveillance

Abstract

Objectives: To study the prognostic features of Creutzfeldt-Jakob disease (CJD) and shed light on its future therapy.

Design: Retrospective cohort study of a longitudinal national cohort of the Taiwan Centers for Disease Control.

Setting and participants: All patients with suspected CJD are reported to the CJD surveillance unit of the Taiwan Centers for Disease Control. An expert committee discussed the reported cases and designated a consensus-based diagnosis. From 1996 to 2020, a total of 809 cases were referred to the CJD surveillance unit for confirmation; of these, 441 cases (women, n = 230) were determined to be sporadic CJD.

Methods: We investigated the clinical manifestations and laboratory findings for 400 patients diagnosed with definite or probable sporadic CJD. We used Kaplan-Meier analyses and Cox proportional hazards model to identify prognostic factors.

Results: The mean age of onset was 67 ± 9.9 years. The mean survival duration was 13.3 ± 14.2 (median 10) months. The leading clinical symptoms were myoclonus (73%) and akinetic mutism (54%). For PRNP polymorphism, 99% of patients (195/197) showed a methionine homozygous genotype at codon 129 (M129M). The sensitivity of periodic sharp wave complexes (PSWCs) on electroencephalograms (EEGs) was 59.7%. The sensitivity of cerebrospinal fluid 14-3-3 protein and total tau protein (>1200 pg/mL) were 69.7% and 75.6%, respectively. Younger patients lived longer than those aged ≥65 years [hazard ratio (HR) 0.466, P < .001]. Women had a better survival probability in the first 3 years than their male counterparts (HR 0.712, P = .005). PSWCs had a persistent negative effect on survival (HR 0.788, P < .05). Although uncommon, epileptic seizures were the only clinical prognostic factor for survival time (HR 0.768, P < .05). PSWCs can be used as an EEG biomarker for prognosis. Epileptic seizures, though not common, are the only clinical prognostic factor for a short survival.

Conclusions and implications: We found that a lower age of onset and female gender favor the survival of patients with sCJD. PSWCs are EEG biomarkers unfavorable for survival, and so are epileptic seizures.

Keywords: 14-3-3; Cortical ribbon signs; epileptic seizure; periodic sharp wave complexes; tau.