Diagnosis and treatment of rapidly progressive dementias

Paterson, Ross W.; Takada, Leonel Tadao; Geschwind, Michael D.

doi:10.1212/cpj.0b013e31826b2ae8

Cited by 74 publications

(87 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In more than 270 cases, however, we confirmed the diagnosis of human prion disease. 9,10 We have previously published on nonprion causes of, and the diagnostic evaluation for, rapidly progressive dementia 9,10 ; this will be updated in the upcoming Continuum issue on dementia.…”

Section: Introductionmentioning

confidence: 99%

Prion Diseases

Geschwind¹

2015

CONTINUUM: Lifelong Learning in Neurology

145

216

View full text Add to dashboard Cite

Purpose of Review This article presents an update on the clinical aspects of human prion disease, including the wide spectrum of their presentations. Recent Findings Prion diseases, a group of disorders caused by abnormally shaped proteins called prions, occur in sporadic (Jakob-Creutzfeldt disease), genetic (genetic Jakob-Creutzfeldt disease, Gerstmann-Sträussler-Scheinker syndrome, and fatal familial insomnia), and acquired (kuru, variant Jakob-Creutzfeldt disease, and iatrogenic Jakob-Creutzfeldt disease) forms. This article presents updated information on the clinical features and diagnostic methods for human prion diseases. New antemortem potential diagnostic tests based on amplifying prions in order to detect them are showing very high specificity. Understanding of the diversity of possible presentations of human prion diseases continues to evolve, with some genetic forms progressing slowly over decades, beginning with dysautonomia and neuropathy and progressing to a frontal-executive dementia with pathology of combined prionopathy and tauopathy. Unfortunately, to date, all human prion disease clinical trials have failed to show survival benefit. A very rare polymorphism in the prion protein gene recently has been identified that appears to protect against prion disease; this finding, in addition to providing greater understanding of the prionlike mechanisms of neurodegenerative disorders, might lead to potential treatments. Summary Sporadic Jakob-Creutzfeldt disease is the most common form of human prion disease. Genetic prion diseases, resulting from mutations in the prion-related protein gene (PRNP), are classified based on the mutation, clinical phenotype, and neuropathologic features and can be difficult to diagnose because of their varied presentations. Perhaps most relevant to this Continuum issue on neuroinfectious diseases, acquired prion diseases are caused by accidental transmission to humans, but fortunately, they are the least common form and are becoming rarer as awareness of transmission risk has led to implementation of measures to prevent such occurrences.

show abstract

Section: Introductionmentioning

confidence: 99%

Prion Diseases

Geschwind¹

2015

CONTINUUM: Lifelong Learning in Neurology

145

216

View full text Add to dashboard Cite

show abstract

“…In general, dementia has a reduced life expectancy [1,2], but survival is highly variable with reported median survival times ranging from 3-13 years after onset or diagnosis [1][2][3][4][5][6]. However, a subgroup deteriorates faster and dies within years or even months [5,7,8]. Little is known about this group of rapid progressors or their cause of death.…”

Section: Introductionmentioning

confidence: 99%

“…A rapid clinical course is one of the hallmarks of prion diseases like Creutzfeld-Jakob disease (CJD) [9], but also Alzheimer's disease (AD), dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and vascular dementia (VaD) occasionally display a rapid course to death [8]. Rapid mortality is clinically highly relevant, as this information could help advanced care planning.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, former studies studied factors related to time to mortality [1, 3-5, 10, 11], rather than specifically focusing on rapid mortality. In addition, although literature on rapidly progressive dementia is slowly emerging [7,8,13], the main emphasis lays on case reports, or diagnostic workup to exclude non-neurodegenerative causes, but not on mortality.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Dementia and Rapid Mortality: Who is at Risk?

Staekenborg

Pijnenburg

Lemstra

et al. 2016

JAD

View full text Add to dashboard Cite

Abstract.Background: Dementia is typically known for its insidious onset and slowly progressive course, but a subgroup deteriorates fast and dies within years or even months. Objective: The purpose of this study was to characterize dementia patients with a rapidly progressive course to death and evaluate their cause of death. Methods: We retrospectively included all patients from the Amsterdam Dementia Cohort who died within two years after diagnosis. We evaluated the characteristics of these rapid progressors and compared them to patients known to be alive two years after diagnosis ('non-rapid mortality'). Results: We included 129 dementia patients (13% of our total cohort with known follow-up) with rapid mortality (age 72 ± 10 y [29% <65 y], 70[55%]M, MMSE 20 ± 5). Mean(SD) survival was 12 ± 7 months. Compared to non-rapid mortality patients (n = 892; age 68 ± 9, 503(56%)M, MMSE 22 ± 5), patients with rapid mortality were slightly older at time of diagnosis, had lower MMSE scores, more depressive symptoms and higher prevalence of a cardiovascular history (all p < 0.05). Alzheimer's disease (AD, 43%) was most frequent in patients with rapid mortality, but the occurrence was much lower compared to non-rapid mortality patients (71%), while all other dementia diagnoses, especially Creutzfeldt-Jakob disease (CJD), vascular dementia (VaD), and frontotemporal dementia (FTD), were more frequent (p < 0.001). There were no specific characteristics for AD patients with rapid versus non-rapid mortality, especially APOE genotypes and CSF-profiles were comparable (p > 0.70). Cause of death was highly variable without a clear relation to dementia diagnosis, with exception of dementia itself in CJD, intracerebral hematoma in VaD, and motor neuron disease in FTD. Conclusions: Short survival is relatively common (∼13% in our cohort) and occurs in all different types of dementia, with overrepresentation of non-AD dementias like CJD, VaD, and FTD.

show abstract

“…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]. Positive amyloid biomarkers, detected via Aβ42 levels in the CSF or on amyloid-positron emission tomography (PET), have been associated with the presence of moderate or frequent neuritic plaques in neuropathological study [8,9], and have thus been proposed in the diagnostic work-up in selected cases of dementia, such as atypical presentations of AD (e.g.…”

Section: Introductionmentioning

confidence: 99%

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

Grau‐Rivera

Gelpí²,

Nos³

et al. 2015

Neurodegener Dis

View full text Add to dashboard Cite

Background: Rapidly progressive dementia (RPD) is caused by a heterogeneous group of both neurodegenerative and non-neurodegenerative disorders. The presence of concomitant pathologies, mainly Alzheimer's disease (AD), may act as a confounding variable in the diagnostic process of this group of diseases. Objectives: We aimed to describe clinicopathological features, including Alzheimer's co-pathology, and diagnostic accuracy in a postmortem series of RPD. Methods: Retrospective analysis of 160 brain donors with RPD (defined as 2 years of disease duration from the first symptom to death) registered at the Neurological Tissue Bank of the Biobanc-Hospital Clínic-IDIBAPS, from 2001 to 2011. Results: Prion diseases were the most frequent neuropathological diagnosis (67%), followed by non-prion neurodegenerative pathologies (17%), mostly AD and dementia with Lewy bodies, and non-neurodegenerative diseases (16%). We observed clinicopathological diagnostic agreement in 94% of the patients with prion RPD but only in 21% of those with non-prion RPD. Four patients with potentially treatable disorders were diagnosed, while still alive, as having Creutzfeldt-Jakob disease. Concomitant pathologies were detected in 117 (73%). Among all RPD cases, 51 presented moderate or frequent mature β-amyloid plaques (neuritic plaques), which are considered to be associated with positive amyloid biomarkers in vivo. Conclusions: Prion diseases were accurately identified in our series. In contrast, non-prion RPD diagnosis was poor while the patients were still alive, supporting the need for better diagnostic tools and confirmatory neuropathological studies. The presence of concomitant AD pathology in RPD should be taken into account in the interpretation of amyloid biomarkers.

show abstract

Diagnosis and treatment of rapidly progressive dementias

Cited by 74 publications

References 38 publications

Prion Diseases

Prion Diseases

Dementia and Rapid Mortality: Who is at Risk?

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

Contact Info

Product

Resources

About