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Case Report: Sporadic Creutzfeldt–Jakob disease initially misdiagnosed as ischemic stroke: a diagnostic challenge and biomarker-based clarification

Year: 2026

Type: article

Abstract: Background: Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare and uniformly fatal prion disorder characterized by rapidly progressive dementia and heterogeneous neurological manifestations. Early sCJD may be misinterpreted as cerebrovascular disease, particularly when focal neurological deficits, unilateral diffusion abnormalities, and vascular risk factors coexist. Case presentation: We report a 76-year-old man with a history of hypertension who initially presented with dizziness and gait instability, followed by progressive right-sided weakness, and was initially diagnosed with ischemic stroke in the setting of intracranial arterial stenosis. Despite antiplatelet and vascular management, the patient experienced rapid cognitive decline, psychiatric disturbances, aphasia, and progressive hemiparesis. Follow-up MRI demonstrated progressive, non-territorial cortical ribbon-like diffusion restriction predominantly involving the left insular, parietal, frontal, and temporal cortices. CSF analysis revealed markedly elevated total tau (4553.50 pg/mL; laboratory-reported cutoff: < 399 pg/mL), phosphorylated tau (66.93 pg/mL; laboratory-reported cutoff: < 50 pg/mL), and 14-3-3γ protein (50515 AU/mL; laboratory-reported cutoff: < 20,000 AU/mL). Autoimmune encephalitis antibodies and metagenomic next-generation sequencing were negative. PRNP genetic testing detected no pathogenic variant in the patient and his son. EEG showed diffuse slowing without periodic sharp wave complexes. According to the 2017 International CJD Surveillance Network criteria, the diagnosis was classified as probable sCJD on the basis of rapidly progressive cognitive impairment, two clinical features (documented cerebellar ataxia and pyramidal signs), characteristic MRI abnormalities, and positive CSF 14-3-3; the typical EEG criterion was absent and RT-QuIC was not performed. Conclusion: This case highlights the diagnostic challenge of early sCJD initially misdiagnosed as ischemic stroke in the presence of coexisting vascular pathology. Recognition of non-vascular diffusion patterns, careful reassessment of atypical clinical progression, and adjunctive CSF biomarker assessment may facilitate timely diagnostic reconsideration and help avoid unnecessary interventions.

Source: Frontiers in Cellular Neuroscience

DOI: 10.3389/fncel.2026.1938627

Authors: Wenjie Hao, Xuan Zhou, Meixia Wang, Wenming Yang, Ting Cheng

Institution: Anhui University of Traditional Chinese Medicine

Language: English

Topic: Prion Diseases and Protein Misfolding

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801