We describe a case of sporadic CJD (sCJD) with slow progression and highlight certain prolonged-progressing sCJD subtypes and genetic forms, which are underrepresented in literature.

A 62-year-old man presented with a four-day history of progressive gait imbalance and intermittent word-finding difficulty. Examination revealed cerebellar dysfunction (gait ataxia, tremor, nystagmus), myoclonus and mild cognitive dysfunction. Brain MRI showed bilateral hyperintensities in parieto-occipital cortices on DWI, suggesting cortical ribboning, but without basal ganglia involvement. Workups for vascular, metabolic, and infectious/autoimmune etiologies returned negative. CJD was then discussed based on the possible cortical ribbon sign and clinical syndrome. However, EEG and CSF analysis for 14-3-3 and Tau proteins were negative. 

Sixteen months later, patient was readmitted with rapid deterioration, aggression, personality change, and severe aphasia. Brain MRI showed progression of the known cortical hyperintensities, again without any basal ganglia abnormalities. At this time, repeated CSF analysis revealed markedly elevated Tau (1639 pg/mL) and (+) 14-3-3 protein. RT-QuIC then confirmed pathological prion proteins. PRNP gene mutations were tested for genetic forms due to slow clinical progression, which returned negative. 

 Eventually, a diagnosis of sporadic CJD was made based on age of onset and clinical course, suggesting one of the slow-progressing sCJD subtypes. The patient quickly developed akinetic mutism and severe cognitive dysfunction. He died of pneumonia 17 months after symptom onset and autopsy confirmed the diagnosis.

In early stage of sCJD, prion markers (Tau and 14-3-3 protein) may be negative, which emphasizes the need to repeat testing if clinical suspicion persists. Additionally, recognizing certain slow-progressive CJD subtypes and cortical ribbon sign on MRI can improve diagnostic sensitivity.