What are the key clinical features that differentiate Creutzfeldt-Jakob Disease (CJD) from other neurodegenerative disorders?

Key clinical features that differentiate Creutzfeldt-Jakob Disease (CJD) from other neurodegenerative disorders include its rapid progression, characteristic neurological signs, and distinctive diagnostic findings.

CJD typically presents with a rapidly progressive dementia over weeks to months, which is much faster than the gradual decline seen in common neurodegenerative diseases like Alzheimer's or Parkinson's disease ¹ (Geschwind and Murray, 2018). Early prominent features include myoclonus (sudden, involuntary muscle jerks), cerebellar ataxia, visual disturbances, and pyramidal/extrapyramidal signs, which are less common or appear later in other dementias ¹ (Mastrianni and Roos, 2000).

Another distinguishing clinical hallmark is the presence of periodic sharp wave complexes on electroencephalogram (EEG), which supports the diagnosis of CJD but is not typical in other neurodegenerative disorders ¹ (Geschwind and Murray, 2018). Cerebrospinal fluid (CSF) analysis may reveal 14-3-3 protein and other prion-related biomarkers, aiding differentiation from other dementias ¹ (Mastrianni and Roos, 2000).

Unlike other neurodegenerative diseases, CJD often lacks a prolonged prodromal phase and shows rapid neurological decline leading to akinetic mutism within months ¹ (Geschwind and Murray, 2018). Sporadic fatal insomnia, a prion disease variant, may present with prominent sleep disturbances, which are not typical in other dementias (Barash, 2025).

In summary, the rapid clinical course, early myoclonus, characteristic EEG and CSF findings, and absence of a prolonged prodrome are key features that differentiate CJD from other neurodegenerative disorders ¹ (Mastrianni and Roos, 2000; Geschwind and Murray, 2018; Barash, 2025).