Diagnosing variant Creutzfeldt-Jakob disease: a retrospective analysis of the first 150 cases in the UK

Heath, Craig; Cooper, Sarah; Murray, Katy; Lowman, Andrea; Henry, Colm; Macleod, Margaret-Ann; Stewart, G.; Zeidler, Martin; McKenzie, J. M.; Knight, Richard; Will, Robert

doi:10.1136/jnnp.2010.232264

Cited by 38 publications

(39 citation statements)

References 15 publications

(11 reference statements)

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“…Compared with most cases of sCJD, vCJD shows slightly slower progression (mean disease duration 14.5 months) 233 , with a prolonged prodromal phase typically dominated by psychiatric symptoms. At more-advanced stages, however, vCJD is clinically indistinguishable from sCJD.…”

Section: Prion Diseasementioning

confidence: 91%

“…In rare cases, prion disease is acquired, giving rise to variant CJD (vCJD). The majority of these cases (about 200) occurred in the UK and France in the past two decades, and were associated with consumption of cattle affected by bovine spongiform encephalopathy 233 . Finally, prion disease can be acquired iatrogenically via cadaveric transplants, human-derived hormones (growth hormone) or medical instrumentations 234 , or via cannibalism — a condition known as kuru, the historic disease of the Fore tribe in Papua New Guinea 235 .…”

Section: Prion Diseasementioning

confidence: 99%

“…All but one of the reported cases of vCJD were homozygous for methionine (MM) at codon 129 (REF. 233). …”

Section: Prion Diseasementioning

confidence: 99%

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A clinicopathological approach to the diagnosis of dementia

2017

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The most definitive classification systems for dementia are based on the underlying pathology which, in turn, is categorized largely according to the observed accumulation of abnormal protein aggregates in neurons and glia. These aggregates perturb molecular processes, cellular functions and, ultimately, cell survival, with ensuing disruption of large-scale neural networks subserving cognitive, behavioural and sensorimotor functions. The functional domains affected and the evolution of deficits in these domains over time serve as footprints that the clinician can trace back with various levels of certainty to the underlying neuropathology. The process of phenotyping and syndromic classification has substantially improved over decades of careful clinicopathological correlation, and through the discovery of in vivo biomarkers of disease. Here, we present an overview of the salient features of the most common dementia subtypes — Alzheimer disease, vascular dementia, frontotemporal dementia and related syndromes, Lewy body dementias, and prion diseases — with an emphasis on neuropathology, relevant epidemiology, risk factors, and signature signs and symptoms.

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Section: Prion Diseasementioning

confidence: 91%

Section: Prion Diseasementioning

confidence: 99%

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A clinicopathological approach to the diagnosis of dementia

2017

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“…They are classified by both clinicopathological syndromes and etiology with subclassification according to molecular criteria (Wadsworth and Collinge, 2011;Safar, 2012). Human prion diseases are grouped into three etiologic categories (Table 4): (1) sporadic Creutzfeldt-Jakob disease (sCJD) -age at onset 50-78 (mean 60) years, mean duration 5 months -, sporadic familial insomnia (sFI), and the recently described variably protease-sensitive prionopathy (VPSPr) (Zhao et al, 2010;Gambetti et al, 2011b); (2) inherited (genetic or familial) forms such as Gerstmann-Sträussler-Scheinker disease (GSS), fatal familial insomnia (FFI), octapeptide repeat insert (OPRI) (Cochran et al, 1996;Jansen et al, 2011), rare familial prion disease with AD-like tau pathology (Jayadev et al, 2011), genetic CJD associated with the E200K mutation , and (3) acquired forms, such as iatrogenic CJD (iCJD), Kuru, and variant CJD (vCJD) (transmission of bovine spongiform encephalopathy/BSE/ to humans) -age at onset 12-74 (mean 27) years, mean duration 14 months (Heath et al, 2011). More than 80% of human prion diseases manifest as sCJD with an incidence of 1-2 cases per million population per year across the world.…”

Section: Frontotemporal Lobe Degeneration (Ftld)mentioning

confidence: 99%

Challenges in the Neuropathological Diagnosis of Dementias

2013

IJN

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Dementia, defined as deterioration in several cognitive domains, is a major public health problem that threatens to become the scourge of the 21th century. It is caused by dysfunction/loss of synapses and neurons inducing default neuronal networks. Consensus criteria for the diagnosis of different dementia disorders have recently been updated. Clinical diagnostic accuracy using revised research criteria and new chemical, imaging and genetic biomarkers ranges from 65 to 96% (for Alzheimer disease), with a sensitivity versus other dementias of 71 to 87% and specificity of 44 to 71%. Morphological assessment, using immunohistochemistry, molecular biological and genetic methods and based on homogenous definitions, harmonized inter-laboratory methods and assessment standards, can achieve a diagnosis/classificaion in almost 99%, without, however, clarifying the etiology of most of these disorders. The new National Institute on Aging-Alzheimer Association (ABC) guidelines for pathological diagnosis of Alzheimer disease combine β-amyloid plaque phases, Braak neurofibrillary and neuritic plaque scores, also considering other pathologies. Major difficulties arise from recent separation of distinct clinico-pathological subtypes (tangle-and plaque intensive, tangle predominant, limbic-predominant and -sparing) from classical Alzheimer disease. Revised research criteria are available for dementia with Lewy bodies, Parkinson disease-dementia, frontotemporal lobe degeneration, vascular cognitive impairment/dementia, prion diseases, and other neurodegenerative dementias. However, due to considerable overlap between various neurodegenerative proteinopathies and cases with mixed pathologies, human postmortem studies entail numerous biases that affect both their general applicability and the validity of correlations. Although most neurodegenerative dementias are incurable at present, concerted prospective clinico-pathological studies using validated protocols and data fusion are required to overcome the limitations of the current diagnostic framework as a basis for efficient new therapy options.

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“…They are classified by both clinicopathologic syndromes and etiology with subclassification according to molecular criteria [190,191]. Human prion diseases are grouped into three etiologic categories [192,193]: (1) Idiopathic forms: sporadic Creutzfeldt-Jakob disease (sCJD) -age at onset 50-78 (mean 60) years, mean duration 5 months, sporadic familial insomnia (sFI), and the recently described variably proteasesensitive prionopathy [194]; (2) inherited (genetic or familial) forms such as Gerstmann-Sträussler-Scheinker disease (GSS), fatal familial insomnia (FFI), octapeptide repeat insert [195,196], rare familial prion disease with AD-like tau pathology [197], genetic CJD associated with the E200K mutation [198], and (3) acquired forms, such as iatrogenic CJD (iCJD), Kuru, and variant CJD (vCJD) (transmission of bovine spongiform encephalopathy/BSE/ to humans) -age at onset 12-74 (mean 27) years, mean duration 14 months [199]. More than 80% of human prion diseases manifest as sCJD with an incidence of 1-2 cases/ million population/year across the world.…”

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confidence: 99%

Neuropathology of Dementia Disorders

Jellinger¹

2014

J Alzheimers Dis Parkinsonism

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IntroductionDementia, encompassing deficits in several cognitive domains that are severe enough to interfere with daily functioning [1], in the new DSM V classification is classified within the broad category of major neurocognitive disorders, proposing specific criteria for the various etiologies [2]. Previously defined as the manifestation of deteriorating brain functions over time due to cell deaths in the brain caused by neurodegeneration or any other disease [3], according to recent research dementia is not primarily caused by neuronal cell death/loss, but by dysfunction and loss of synapses [4] in AD [5] and in α-synucleinopathies [6]. Other causes include cholinergic neuronal and axonal abnormalities [7,8], as well as pre-and postsynaptic cortical cholinergic deficits also occurring in early AD [9]. These changes due to disconnection of major nervous circuitries causing default networks [10][11][12][13] have been demonstrated in vivo in early AD [14], suggesting that disease progress is transmitted by neuronal pathways [15]. A prionlike spread of misfolded protein aggregates in the pathogenesis and progression of neurodegeneration is a hot spot of discussion [16][17][18][19][20][21].Both the prevalence and incidence of dementia increase exponentially with age. In 2010, 35.6 million people worldwide lived with dementia, with around 8 million new cases every year. Numbers are expected to double or triple every 5-10 years, to 135 millions in 2050, 16 millions in Europe. In 2010, 58% of all demented people lived in low-cost countries, with their proportion anticipated to rise to 71% in 2050 [22]. According to recent data from China the incidence of dementia was 9.87/1000 person years and the median standardised mortality ratio was 1.94:1 [23]. With the disproportional growth of the elderly population, dementia has become a major public health and socio-economic problem that threatens to become the scourge of our century. The total costs for dementia were US$ 604 billion in 2010 worldwide, up to 70% for social care alone [24], total payments for AD for 2013 were expected to be $ 203 billion in USA alone, not included contributions of unpaid caregivers [25]. Neuropathology of Dementia DisordersKurt A Jellinger* Institute of Clinical Neurobiology, Kenyongasse 18, A 1070, Vienna, Austria AbstractDementia, being not a specific disease but a syndrome characterized by deficits in several cognitive domains, is a major public health and socio-economic problem of our century. It is caused by dysfunction/loss of synapses and neurons inducing default neuronal networks. Despite updated concensus criteria for the clinical diagnosis of the major neurodegenerative disorders and new biomarkers, the diagnostic accuracy ranges from 65 to 96% (for Alzheimer's disease /AD), with a sensitivity versus other dementias of around 85.4% and a specificity of up to 77.7%. Pathologic assessment, using genetic and molecular biological methods, based on homogenous definitions, harmonized interlaboratory and assessment standards, can achiev...

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Diagnosing variant Creutzfeldt-Jakob disease: a retrospective analysis of the first 150 cases in the UK

Cited by 38 publications

References 15 publications

A clinicopathological approach to the diagnosis of dementia

A clinicopathological approach to the diagnosis of dementia

Challenges in the Neuropathological Diagnosis of Dementias

Neuropathology of Dementia Disorders

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