Introduction Sporadic Creuzfeldt-Jakob disease (sCJD) is a rare disease caused by prion proteins and usually presents in the 7th decade of life. sCJD classically presents with a rapidly progressive dementing illness, associated myoclonus and a median time to death of 6 months. Less commonly younger patients are described with a neuropsychiatric presentation and a prolonged disease course. We report two young sCJD patients with neuropsychiatric presentations and slow disease progression admitted to Liverpool Hospital, Sydney (2016–2017).

Case 1 A 48 year old Chinese man presented with a 12 month history of depressive symptoms and insomnia. Over the next 5 months, he developed progressive cognitive impairment, disinhibited behaviour, aggression, paranoia and ataxia of gait. Serial EEG and MRI brain scans, cerebrospinal fluid (CSF) testing for 14–3–3 protein and PRNP gene testing were negative or non-contributory. He progressively became mute, bedbound and died at 24 months from symptom onset. Diagnosis was only confirmed with a limited brain autopsy at post-mortem that revealed severe microvacuolar change, gliosis, neuronal loss and status spongiosus. Anti-prion antibody 12 F10 staining showed a diffuse fine synaptic pattern in the frontal cortex and striatum consistent with sCJD.

Case 2 A 42 year old Afghani man presented with a 36 month history of emotional lability and progressive social withdrawal followed by auditory and visual hallucinations, cognitive impairment and gait ataxia. Screening for vasculitis, infective (including HIV/syphilis) and autoimmune encephalopathies were negative. EEG demonstrated non-specific slowing, without characteristic periodic sharp-wave complexes. MRI brain was initially normal but progress imaging showed bilateral cortical ribboning, caudate nucleus T2-hyperintensity and associated diffusion restriction consistent with sCJD. CSF 14–3–3 protein analysis was positive. The patient died 38 months from symptom onset. Post-mortem examination was not performed.

Conclusions CJD in younger patients may present as a slowly progressive neuropsychiatric disorder and ante-mortem investigations may remain negative. Post-mortem remains the gold standard for CJD diagnosis.