CREUTZFELDT-JAKOB DISEASE: ETIOPATHOGENIC ASPECTS, CLINICAL MANIFESTATIONS, DIAGNOSIS, AND THERAPEUTIC CHALLENGES: A LITERATURE REVIEW

Abstract

Objective: To analyze the etiopathogenic aspects, clinical manifestations, diagnostic methods, and therapeutic challenges of Creutzfeldt-Jakob disease (CJD). Methodology: A critical synthesis was developed based on ten original studies published between 2016 and 2025, covering the period from January 2015 to September 2026. The publications were organized into four thematic areas: etiopathogenesis, clinical manifestations, diagnosis, and therapeutics. The study designs, populations, key findings, and limitations of the research were examined. Results and discussion: The studies revealed variable penetrance of *PRNP* gene variants and susceptibility associations involving *STX6* and *GAL3ST1*, though the mechanisms initiating the sporadic form remain not fully understood. Clinical manifestations included cognitive, cerebellar, motor, and behavioral changes, with variations in presentation and survival across subtypes. Regarding diagnosis, RT-QuIC demonstrated high specificity; its integration into clinical criteria, combined with magnetic resonance imaging (MRI), increased the sensitivity for identifying the disease in living patients. Nevertheless, the investigation of differential diagnoses remains necessary. Studies involving doxycycline and the monoclonal antibody PRN100 failed to establish definitive clinical efficacy, due to limitations such as small sample sizes and reliance on observational comparisons. Conclusion: While the understanding of CJD has advanced in the genetic and diagnostic fields, gaps in etiopathogenesis and therapeutics persist. Early recognition, the integration of diagnostic methods, and multidisciplinary care remain essential, alongside controlled research aimed at developing interventions capable of modifying the course of the disease.