BACKGROUND: Nonconvulsive status epilepticus (NCSE) in patients with confusion may be difficult to distinguish from nonepileptic (metabolic/toxic, postanoxic, and spongiform) encephalopathies. This study aimed to describe the misleading presentation of patients with sporadic Creutzfeldt-Jakob disease (sCJD) who were initially diagnosed with a refractory NCSE (rNCSE). METHODS: We retrospectively reviewed the clinical characteristics, EEG records, brain MRI scans, 14-3-3 protein detection in CSF, genotype of the prion protein gene, and neuropathologic data of patients referred to our neurologic intensive care unit (NICU) with this presentation. RESULTS: Ten patients with a final diagnosis of definite (n = 7) or probable (n = 3) sCJD were referred to our NICU with an initial diagnosis of rNCSE. Reanalysis of the EEG ruled out ictal rhythmic activities, but showed diffuse, periodic, or semiperiodic sharp-wave complexes (PSWC) with short period. PSWC were briefly attenuated by auditory (n = 5) or painful (n = 3) stimuli and by IV injection of antiepileptic drugs (n = 5) but without clinical improvement. In addition, PSWC showed fluctuations according to the vigilance level (n = 5). Brain MRI showed hyperintensities in basal ganglia (n = 9/10) and in cortical areas (n = 7/10). 14-3-3 Protein was detected in CSF (n = 10). Only 2 sCJD subtypes were found (MM1 5/7, MV1 2/7). CONCLUSIONS: This series of patients suggests that sporadic Creutzfeldt-Jakob disease should be considered as a differential diagnosis, rather than as a cause, of apparent refractory nonconvulsive status epilepticus. Criteria for nonconvulsive status epilepticus diagnosis should rely on careful examination of both EEG parameters and clinical state so that aggressive, unnecessary treatments can be avoided.