| Tempo of decline | Days to weeks (infectious, autoimmune, vascular) versus weeks to months (prion, neoplastic, some neurodegenerative) |
| Associated symptoms | Seizures, movement disorders (myoclonus, chorea, ataxia), psychiatric symptoms, systemic illness, fever |
| Risk factors | Family history of Prion Disease, immunosuppression, cancer history, substance exposure, travel history |
| Prodromal features | Psychiatric symptoms preceding cognitive decline raise suspicion for autoimmune encephalitis or Prion Disease |
| Cell count and differential | Pleocytosis suggests infection, autoimmune, or neoplastic causes (usually absent in Prion Disease) |
| Protein and glucose | Elevated protein is nonspecific; low glucose suggests infection or leptomeningeal disease |
| Cytology | For malignant cells |
| 14-3-3 protein and total tau] | Elevated in CJD but nonspecific (sensitivity 85–95%, specificity 40–60% for 14-3-3) |
| Autoantibody panels | Anti-nmda-receptor-R, anti-LGI1, anti-CASPR2, anti-AMPA-R, anti-GABA-B-R, anti-DPPX, anti-IgLON5 |
| Databases | OMIMOrphanetClinicalTrialsPubMed |
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