Rapidly progressive dementia

Abstract

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...

Clinicopathological Correlations and Concomitant Pathologies in Rapidly Progressive Dementia: A Brain Bank Series

“…The neuropathological profile of our series was not different from those previously reported in RPD, except for the high frequency of prion diseases (67%), which was similar to that reported in a previous study also performed in a reference centre for prion disease diagnosis [1]. AD was the second most frequent aetiology, followed by DLB.…”

“…The term ‘rapidly progressive dementia' (RPD) encompasses a heterogeneous group of medical conditions that cause progressive cognitive impairment, leading to functional disability or death within a short period of time, usually less than 24 months [1,2]. Creutzfeldt-Jakob disease (CJD) represents the leading cause of RPD.…”

“…Creutzfeldt-Jakob disease (CJD) represents the leading cause of RPD. However, up to one third of patients with RPD may present other diagnoses, mainly non-prion neurodegenerative (np-ND) diseases like Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) or non-neurodegenerative (non-ND) treatable conditions [1,3,4,5,6]. Clinical diagnosis of RPD is based on an extensive work-up that includes brain magnetic resonance imaging (MRI), electroencephalography (EEG) and blood and cerebrospinal fluid (CSF) studies, often requiring the determination of metabolic, infectious and autoimmune test panels [7].…”

Familial fatal insomnia with atypical clinical features in a patient with D178N mutation and homozygosity for Met at codon 129 of the prion protein gene

“…He concluded that 62% of all patients had prion disease, and in 38% of the non prion RPD patients, neurodegenerative diseases accounted for 39% of cases, autoimmune for 22%, and unknown cause for 12%. 9 Rapidly progressive neurodegenerative diseases such as Lewy Body Dementia (LBD), Frontal Temporal disease (FTD), and Cortical Basal-ganglia degeneration (CBD), were included our patient's differential diagnoses, due to patient's overall cognitive decline, visual hallucinations, and extra-pyramidal symptoms. Autoimmune encephalitis was also considered, given his acute onset and progression of symptoms, but this was ruled out due to lack of autoimmune antibody index and an ineffective trial of high dose corticosteroid therapy.…”

Challenges in the Neuropathological Diagnosis of Dementias

“…In contrast to most dementing conditions that typically develop over years, rapidly progressive dementia (RPD) being quickly fatal is one of the most challenging problems. The differential diagnosis is often widely ranging, and, in addition to frequent prion diseases includes rapidly progressing neurodegenerative tauopathies and synucleinopathies, autoimmune condition infections, toxic-metabolic and neoplastic diseases (Geschwind et al, 2008;Josephs et al, 2009). According to the US National Prion Disease Pathology Surveillance Center (NPDPSC) in patients with RPD, treatable disorders are frequently mistaken for CJD.…”