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Iatrogenic Creutzfeldt-Jacob Disease (iCJD) was historically caused by corneal or dural transplants, contaminated neurosurgical tools, or administration of cadaveric pituitary hormones. It is believed to have been largely eradicated. Current iCJD diagnostic criteria don’t recognize solid organ transplant as a viable transmission pathway. 3 singular cases of Creutzfeldt-Jacob disease (CJD) following an organ transplant have been described but are thought to have been sporadic CJD (sCJD) developed incidentally after the procedure.
Here we present concurrent definite and probable sCJD diagnoses in two kidney recipients. We hypothesize a possible transmission from their common donor.
Case I
A 51-year-old male 4 months after a kidney transplantation presented with a fever of unknown origin, dry cough, headache, and general weakness that had persisted for a week. He was slow to respond and exhibited bilateral asymmetric ptosis and dysmetria.
Immunosuppressive drug neurotoxicity and CMV neuroinfection were ruled out. Routine serologic and NAAT-based infection testing yielded no results. Brain MR (Fig. 1) showed multiple partially confluent foci and hyperintense areas in the white matter and the brainstem in FLAIR sequence. The Robin-Virchow perivascular spaces were widened.
In two weeks, the patient developed dysphagia, aphasia and a positive right-sided Babinski sign. Rapid cognitive impairment ensued. His mental state was highly fluctuating with periods of total unresponsiveness to verbal stimuli.
Further testing yielded a positive 14-3-3 CSF assay, which, combined with imaging and clinical features led to the diagnosis of probable sCJD; diagnostic criteria were met. Due to the progressive, fatal character of the disease, the patient is being treated conservatively.
Case II
Concurrently, a female recipient of a kidney from the same donor was hospitalized after presenting with a seven-day history of tinnitus and subsequent rapid onset of nearly complete deafness, diplopia, aphasia and bilateral positive Babinski sign. She developed profound dementia and flaccid paralysis and died 34 days after admission. A definitive diagnosis of sCJD was established with neuropathology.
The two cases meet the CDC criteria for, respectively, probable and definite sCJD; however, the short presumed incubation period of 4 months may point to diagnoses of de novo sCJD in the female patient and a different, unspecified neurodegenerative disease in the male. The real-time quaking-induced conversion (RT-QuIC) test was not available to further confirm his diagnosis. No donor specimens were available to be tested for prions. All these reasons support the designation of this occurrence as only a possible transmission, according to the definitions of imputability for donor origin infectious diseases transmission.
This report highlights the need for heightened vigilance in screening organ donors, and for wider adoption of advanced diagnostic tools like RT-QuIC. Further investigation is warranted to assess whether iCJD diagnostic criteria should include solid organ transplantation as a potential exposure. Seeking transmission pathways of uncertain significance is vital for the implementation of new preventative public health measures.
