The longest survivor of Creutzfeldt-Jakob disease with V180I mutation.

Abstract

Creutzfeldt-Jakob disease (CJD) is a rapidly progressive, transmissible human prion disease. The disease is classified into sporadic, genetic, and acquired form. Majority CJD cases are sporadic, and genetic CJD (gCJD) consists 10-15% of all CJD cases. In genetic cases, survival is more prolonged than in sporadic CJD, and the average disease duration of V180I gCJD patients is known as 23 to 27 months. We report a V180I gCJD patient who survived for 16 years, the longest at present. A longitudinal observation was conducted from March 2004 to November 2020 as the patient was expired. We analyzed clinical symptoms, cerebrospinal fluid (CSF), brain MRI, EEG, prion protein gene (PRNP) sequencing, and brain biopsy which were done at a time of diagnosis. A 57-year-old patient, previously healthy, reported cognitive decline, depression, loss of appetite, and tremors in her left hand. Neurological evaluation was unremarkable except fine postural tremor in her left hand. Brain MRI showed abnormal high signals in the right basal ganglia and bilateral frontotemporal cortices without atrophy. CSF analysis was weakly positive of 14-3-3 protein and EEG presented no periodic sharp-wave complexes. Sequencing of PRNP revealed V180I mutation. Also, brain biopsy of frontal cortex was conducted, and histopathological findings showed spongiform changes with neuronal loss. The patient presented akinetic mutism and became bed-ridden with tube feeding within 6 months. She received long-term home care with regularly visiting nursing services and died of pneumonia 198 months (16 years) after symptom onset. To our knowledge, this is the first report of CJD who lived more than 16 years after onset. Our patient showed several known characteristics of V180I gCJD, however, the life span exceeded its mean survival period. The exact cause of this patient's long-term survival is elusive. Mild involvement of brain stem and appropriate long-term care suggested by current study may give beneficial for the patient.