To demonstrate an RT-QuIC negative case of sporadic Creutzfeldt-Jakob disease (VV1-2)

Creutzfeldt-Jakob disease (CJD) is a rapidly progressive neurodegenerative disease caused by the propagation and buildup of abnormal prion proteins. There are three main types: sporadic (most common), familial, and acquired. Sporadic CJD is further categorized based on the prion protein gene (PRNP) and the scrapie prion protein (PrPsc). We present a case of VV homozygous and mixed type (1-2) sCJD.

A 62-year-old male presented after developing progressive ataxia, muscle twitching, and mild cognitive decline over a two-month period. Initial investigations, consisted of routine blood tests, heavy metal screening and a brain MRI brain. These studies were unrevealing for an etiology. He rapidly developed hallucinations and confusion within a few weeks. Repeat MRI brain revealed hyperintensities in bilateral thalami and caudate head. Myoclonic jerks and severe cognitive decline followed in the subsequent weeks. An EEG showed diffuse slowing, but no periodic sharp waves. CSF testing showed elevated 14-3-3 protein and was negative for tau and RT-QuIC. He deteriorated further and developed akinetic mutism. The patient soon expired. Whole brain autopsy and genetic testing for CJD were performed.

Autopsy and genetic testing confirmed the VV homozygous mixed type (1-2) sporadic CJD. CSF testing of 14-3-3 protein levels, neuroimaging, and clinical symptoms of ataxia, myoclonic jerks, and rapid dementia further supported the diagnosis.

RT-QuIC is a significant diagnostic tool for CJD, but it may fail to detect abnormal prion proteins in atypical cases or if done too early in the disease course. In our case, the CSF test was negative 17 days pre-mortem, possibly due to the mixed type PrPsc. A diagnosis of CJD should therefore encompass various factors: clinical signs, imaging, EEG, and CSF results. Post-mortem pathological and genetic testing remain the definitive diagnostic standards for CJD.