In contrast with more common dementing conditions that typically develop over years, rapidly progressive dementias can develop subacutely over months, weeks, or even days and be quickly fatal. Because many rapidly progressive dementias are treatable, it is paramount to evaluate and diagnose these patients quickly. This review summarizes recent advances in the understanding of the major categories of RPD and outlines efficient approaches to the diagnosis of the various neurodegenerative, toxic-metabolic, infectious, autoimmune, neoplastic, and other conditions that may progress rapidly.New and dramatic advances related to the diagnosis and treatment of conditions that present as rapidly progressive dementia (RPD) have led to more precise classification schemas and diagnostic approaches. Improved magnetic resonance imaging (MRI) techniques allow delineation of most patients with Creutzfeldt-Jakob disease (CJD) from those with other RPDs. Also, a better understanding of neurodegenerative conditions has helped to delineate non-CJD RPDs from each other and from CJD. Previously nonendemic infectious disorders, such as West Nile virus, have appeared in the United States and must be considered in the differential diagnosis of RPD. Finally, an explosion of research related to autoimmune brain disorders, caused by neoplasms or unknown precipitants, has led to the discovery of antibodies associated with an eminently treatable group of RPDs. This review emphasizes these advances and offers a new and modern classification schema for RPDs. In addition, this article emphasizes the MRI features of CJD versus other RPDs, delineates the common infectious causative agents for RPD, and describes new findings related to autoimmune entities that cause RPD.
Experience in a Rapidly Progressive Dementia Referral CenterIn 2001, Stanley Prusiner's laboratory at the University of California, San Francisco (UCSF) 1 demonstrated the potential therapeutic efficacy of both quinacrine and chlorpromazine in an experimental model of prion disease. This finding led to a dramatic increase in referrals for suspected prion disease to UCSF, and over the past 6 years we have conducted comprehensive evaluations on 178 cases of suspected prion disease or RPD (Fig 1). We made a conclusive diagnosis in 95.5% of these patients, whereas in 4.5%, the diagnosis was dementia, leukoencephalopathy, or encephalopathy of unknown origin. Sixty-two percent of all patients had prion disease, which was sporadic in 75% (72% were pathology proved), genetic in 22%, and acquired in 3% (variant or iatrogenic). In 38% of the RPD patients, we diagnosed a nonprion condition; typically, these cases were diagnostically complex, defying diagnosis The largest group of nonprion patients in the UCSF cohort had neurodegenerative diseases, which were found in 14.6% of all cases, accounting for 39% of all nonprion cases. These nonprion dementing conditions included frontotemporal dementia (FTD), corticobasal degeneration (CBD), Alzheimer's disease (AD), dementia with Lewy bodie...
