Rapidly Progressive Dementia

Today we discussed a fascinating and very sad case of a woman with rapidly progressive dementia over a 3 week period. We discussed the broad differential diagnosis for this phenomenon which includes:

• Neurodegenerative conditions including Creutzfeldt-Jacob disease, other dementias and progressive supranuclear palsy.
• Infectious conditions like HSV encephalitis or HIV dementia, subacute sclerosing panencephalitis following measles infection in young adults, and syphilis.
• Metabolic conditions like B12 deficiency, Wernicke's encephalopathy from thiamine deficiency, and liver/renal failure.
• Toxins like Lead, Lithium, Mercury, Arseni, or bismuth.
• Autoimmune phenomenon like Hashimoto's encephalopathy, CNS vasculitis, or lupus cerebritis.
• Paraneoplastic limbic encephalopathy.
• Metastases or primary CNS malignancies.

We discussed the possibility of prion disease, or Creutzfeldt-Jacob disease at length today. CJD is a transmissible spongiform encephalopathy that is uniformly fatal - variant forms (ie acquired) often within 3 months and sporadic within 6. Although the incubation period is incredibly long (years), CJD progresses rapidly once symptoms appear. It is characterized by:

• dementia, diminished higher-level cortical function, and mood changes
• myoclonus
• extrapyramidal signs like hypokinesia and cerebellar signs like ataxia and nystagmus.

Diagnosis is made with the support of a number of modalities, most of which do not allow for rapid or definitive diagnosis, and lack sensitivity or specificity. These include MRI which often shows increased T2 and FLAIR signal intensity in the putamen and head of the caudate, EEG showing periodic synchronous bi- or triphasic sharp wave complexes (specific, not sensitive), and CSF (normal glucose, often (60%) normal protein levels, and presence of abnormal protein 14-3-3).

Unfortunately there is no treatment for CJD and death invariably occurs within months. This is all the more reason why it is important to search for the other, potentially reversible causes of rapidly progressing dementias. See this great review for a some very helpful algorithms outlining the approach to investigation.