Creutzfeldt-Jakob disease following SARS-CoV-2 infection with rapid neurological decline: a case report

Abstract

Case Presentation: A 72-year-old woman with hypertension, type 2 diabetes mellitus, and Hashimoto’s thyroiditis was admitted with a 10-day history of speech impairment and right upper limb weakness. Neurological examination showed expressive dysphasia with preserved repetition and naming, and muscle strength graded as IV (+) in the right upper limb. Brain MRI revealed multiple cortical areas of diffusion restriction and T2/FLAIR hyperintensities involving bilateral the parietal, occipital, frontal, and temporal regions, as well as the posteromedial aspect of the left thalamus. A vascular etiology was excluded, raising suspicion of autoimmune encephalitis or prion disease. The patient received methylprednisolone and intravenous immunoglobulin without clinical improvement. EEG demonstrated posterior rhythm disorganization with theta–delta slowing and epileptiform discharges in the left hemisphere. CSF was positive for 14-3-3 protein. A previous SARS-CoV-2 infection was identified. Subsequently, rapidly progressive neurological deterioration occurred, with gait ataxia, left-sided dysmetria, and sporadic myoclonus, supporting Creutzfeldt-Jakob disease. After discussion with the patient and family, invasive measures were withheld in accordance with advance directives. The patient remained under palliative care and died on March 31, 2024, approximately 10 weeks after hospital admission and 11 weeks after symptom onset. Discussion: This case is particularly relevant due to its initial presentation mimicking a cerebrovascular event, followed by rapid neurological deterioration and diagnostic findings consistent with sporadic Creutzfeldt-Jakob disease. Creutzfeldt-Jakob disease is a rare, rapidly progressive, and invariably fatal prion disorder characterized by neurodegeneration resulting from abnormal protein misfolding, typically presenting a short clinical course after symptom onset. The sporadic form accounts for more than 80% of cases, with a global incidence of approximately 1–2 cases per million individuals per year, predominantly affecting individuals older than 60 years, with increasing incidence with age. Although a causal relationship between COVID-19 and prion diseases remains unproven, recent reports have suggested a possible temporal association. Increasing attention has been directed toward the role of systemic inflammation in accelerating neurodegenerative processes. In this context, the cytokine-mediated inflammatory response associated with SARS-CoV-2 infection may act as a potential trigger or modulator of disease progression. Final Comments: This case underscores the importance of considering prion diseases in the differential diagnosis of subacute focal neurological deficits associated with rapidly progressive cognitive decline, particularly when the initial presentation mimics more common conditions such as stroke, in the context of recent systemic infection.