Prion-Related Diseases Differential Diagnoses

Updated: Jun 02, 2021
  • Author: Deepak K Gupta, MD; Chief Editor: Niranjan N Singh, MBBS, MD, DM, FAHS, FAANEM  more...
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Diagnostic Considerations

Other problems to be considered include the following:

  • Non-herpes viral encephalitis

  • Diffuse Lewy body disease

  • Chronic meningitis

  • Dementia as a paraneoplastic syndrome

  • Familial myoclonic dementia

  • Lithium poisoning

  • Dementia in motor neuron disease

  • Limbic encephalitis (and other paraneoplastic syndromes)

  • Hashimoto encephalopathy (or Steroid-responsive encephalopathy associated with autoimmune thyroiditis [SREAT])

Rule out all other causes of dementia, particularly causes of a rapidly progressive dementia that could be treatable, such as herpes encephalitis. [91] In herpes encephalitis, the CSF has pleocytosis and an elevated protein content, while in CJD the cell count and protein content are within the reference range. In addition, herpes encephalitis has characteristic MRI and EEG findings. Other entities that are in the differential diagnosis are neurodegenerative disease such as Alzheimer disease, Pick disease, corticobasal ganglionic degeneration, familial myoclonic dementia, and multisystem atrophy. However, the progression of the dementia and other neurological symptoms is slower in all these disorders compared to CJD.

Also consider Hashimoto encephalitis (also referred to as steroid-responsive encephalopathy associated with autoimmune thyroiditis [STEAT]) in the differential diagnosis. [92, 93, 94] The clinical symptomatology of Hashimoto encephalitis can be very similar to possible CJD, with the presence of a rapidly progressive dementia, myoclonus, ataxia, and psychosis; however, this autoimmune disorder responds well to treatment with immunosuppression. The diagnosis of Hashimoto encephalopathy can be made by finding high serum levels of thyroperoxidase autoantibodies (TPO). Patients with Hashimoto encephalitis do not show the 14-3-3 protein in the CSF nor do they have the typical periodic sharp wave complexes on EEG.

The classical clinical presentation of CJD is quite unique; but with such high clinical variability and a variety of symptoms characteristic of more common neurodegenerative diseases, CJD “mimics” are not uncommon and may present a diagnostic challenge. Clinical features suggestive of a “mimic” rather than CJD include generalized seizures, fevers, and hyponatremia. Additionally, MRI signal hyperintensity outside the striatum, thalamus, or cortex is suggestive of pathology other than CJD. Further, visualizing contrast-enhancing lesions on imaging or obtaining CSF with pleocytosis are highly suggestive of a CJD “mimic." [95]

Differential Diagnoses