Unusual Case of Sporadic Creutzfeldt–Jakob Disease Subtype VV1

A 79-year-old, right-handed woman presented with a 4-month history of progressive cognitive decline, gait changes, upper limb myoclonus, visual hallucinations, and depression. She initially noticed changes in her memory and in her ability to manage numbers, which affected her work. Brain MRI performed within a month of her symptom onset demonstrated subtle bilateral diffusion-weighted imaging signal hyperintensities in limbic structures including the hippocampus, insula, parahippocampal, and lingual gyri. There were no signal abnormalities in the basal nuclei, thalamus, or cerebellum (Figure 1). An EEG demonstrated diffuse slowing and decreased amplitude in the background rhythm. The patient’s Montreal Cognitive Assessment³ score was 2 of 30 (z score=−3.13). Her Neuropsychiatric Inventory Questionnaire score⁴ indicated mild visual hallucinations, disinhibition and appetite, moderate anxiety and motor disturbance, and severe agitation, depression, irritability, and nighttime behaviors, with a total severity score of 16. The patient’s CSF 14-3-3 and tau protein (4,334 pg/mL) levels were suggestive of prion disease. A rapidly progressive dementia workup to rule out metabolic, autoimmune, and infectious etiologies was unrevealing. The patient was provided symptomatic management and was referred to hospice and the Creutzfeldt–Jakob Disease Foundation (www.cjdfoundation.org). The patient died after an illness duration of approximately 5 months. A postmortem examination confirmed the diagnosis of sCJD VV1.²

A literature review of sCJD reveals that the VV1 subtype is the rarest molecular subtype.² In contrast with the classic sCJD phenotype, patients with the VV1 subtype are typically younger, are male, and have longer disease durations.^2,5,6 Previous reports of MRI findings demonstrated that the hippocampus, insula, and temporal cortex are frequently affected in the VV1 subtype, whereas the basal nuclei are rarely involved.⁵ In addition, the limbic structures appear to be frequently affected in this subtype. In our case, diffusion-weighted imaging signal abnormalities were very subtle and no signal abnormality was present on other MRI sequences, including fluid-attenuated inversion recovery. The involvement of the limbic structures also likely explains the prominent neuropsychiatric symptoms in our patient. The above case differed significantly from other VV1 cases in terms of the patient’s older age at disease onset, female gender, and shorter disease duration.

VV1 is a challenging subtype to diagnose, and this report adds further complexity and variation to its clinical characterization. Although PRNP codon 129 polymorphism and the prion protein type exert a large influence on clinical and neuropathologic phenomenology in sCJD, other factors remain unknown and require further study.

The authors thank the National Prion Disease Pathology Surveillance Center and Dr. Pierluigi Gambetti for assistance.