Rapidly progressive dementias and the treatment of human prion diseases

Abstract

Importance of the field: Rapidly progressive dementia (RPD) has many possible etiologies and definitive treatment is reliant upon an accurate diagnosis from an appropriate diagnostic work-up. A large portion of the neurodegenerative causes of RPD are due to prion diseases (e.g., Creutzfeldt–Jakob disease). The study of prion diseases, for which there is no currently available treatment, has public health implications and is becoming increasingly more relevant to our understanding of other protein misfolding disorders including Alzheimer's disease, frontotemporal degeneration, and Parkinson's disease.

Areas covered in this review: This article begins with an overview of the etiologies and diagnostic work-up of RPD followed by a detailed review of the literature concerning the treatment of human prion diseases (1971 to present).

What the reader will gain: The reader will understand the differential diagnosis and work-up of RPD as it pertains to its treatment, as well as an in-depth understanding of treatments of human prion diseases.

Take home message: An accurate diagnosis of the cause of RPD is of paramount importance when determining appropriate treatment. Most studies of the treatment for human prion diseases are case reports or case series, and results from only one randomized, placebo-controlled study have been reported in the literature (flupirtine). Studies have been hindered by disease heterogeneity and lack of standardized outcome measures. Although no effective prion disease treatment has been revealed through these studies, they provide important considerations for future studies.

Keywords::

• Creutzfeldt–Jakob disease
• diagnosis
• doxycycline
• pentosan polysulphate
• prion disease
• quinacrine
• rapidly progressive dementia
• treatment

Acknowledgements

This research was supported in part by the Stempler Fund for Dementia Research, the Richmond Family Fund for Alzheimer's and Related Diseases, and the Alzheimer's Disease Research Center (P50AG05146).

Notes

This box summarizes key points contained in the article.