Rapidly progressing dementias

Dementias which progress from normal cognition to severe dementia in less than 2 years (unofficial definition) (Salardini 2019).

• In addition to cognitive decline, they often have behavioral problems, pyramidal or extrapyramidal symptoms, EEG changes, and myoclonus.

Categories (Salardini 2019)

1. Prion disease – misfolded prions are infectious proteins which cause devastating neurodegenerative illness
   1. Creutzfeldt-Jakob disease (CJD)
      1. Most common form of prion disease
      2. Presents with cognitive symptoms, pyramidal / extrapyramidal motor symptoms, ataxia, myoclonus, and psychiatric symptoms
   2. Fatal familial insomnia (FFI)
      1. Presents with insomnia, dysautonomia, cognitive problems
   3. Gerstmann-Straussler-Schinker syndrome (GSS)
      1. Cerebellar and/or extrapyramidal symptoms
      2. Slow progression over 10-20 years
   4. Kuru
   5. Variant CJD
      1. Caused by eating contaminated meat of livestock with bovine spongiform encephalopathy
2. Atypical presentation of other primary dementias
3. Autoimmune diseases including autoimmune encephalitis
4. Secondary encephalopathies (toxic metabolic encephalopathy)

Diagnostic approach (Geschwind, 2016)

• Initial evaluation
  • establish time course, highlight initial symptoms, r/o delirium
    • autoimmune encephalopathies often affect limbic areas and may present with memory and/or behavioral symptoms
    • viral encephalopathies or acute demyelinating encephalomyelitis may present after flu-like illness
  • screening tests
    • blood studies: CBC, BMP, LFTs, RPR, rheum screen (ESR, ANA, CRP), B12, HIV, medication levels
    • urine studies: u/a, utox (if indicated)
    • CSF: cell count and diferential, protein, glucose, IgG index, oligoclonal bands, VDRL, 14-3-3 protein western blot, Total tau ELISA, neuron specific enolase ELISA, RT-QuIC, cryptococcal antigen, viral PCRs/antibodies/cultures, bacterial/fungal/acid-fast bacilli stains/cultures, cytology, flow cytometry
    • EEG

Imaging

DWI images of 2 patients with suspected CJD (Salardini 2019)

• In axial view of patient A there is characteristic increased cortical signal (cortical ribboning) suggesting cortical cytotoxic edema
• In axial view of patient B there is characteristic increased signal in caudate and mesial thalamus (hockey stick)

References

Geschwind MD. Rapidly progressive dementia. Continuum. Apr:22(2 Dementia):510-537 (2016). https://pubmed.ncbi.nlm.nih.gov/27042906/

Salardini A. An Overview of Primary Dementias as Clinicopathological Entities. Semin. Neurol. 39, 153–166 (2019). https://pubmed.ncbi.nlm.nih.gov/30925609/