Detection of Prions in Brain Homogenates and CSF Samples Using a Second-Generation RT-QuIC Assay: A Useful Tool for Retrospective Analysis of Archived Samples

The possibilities for diagnosing prion diseases have shifted significantly over the last 10 years. The RT-QuIC assay option has been added for neuropsychiatric symptoms, supporting biomarkers and final post-mortem confirmation. Samples of brain homogenates used for final diagnosis, archived for many years, provide the possibility for retrospective studies. We used a second-generation RT-QuIC assay to detect seeding activity in different types of sporadic and genetic prion diseases in archival brain homogenates and post-mortem CSF samples that were 2 to 15 years old. Together, we tested 92 archival brain homogenates: 39 with definite prion disease, 28 with definite other neurological disease, and 25 with no signs of neurological disorders. The sensitivity and specificity of the assay were 97.4% and 100%, respectively. Differences were observed in gCJD E200K, compared to the sporadic CJD group. In 52 post-mortem CSF samples—24 with definite prion disease and 28 controls—we detected the inhibition of seeding reaction due to high protein content. Diluting the samples eliminated such inhibition and led to 95.8% sensitivity and 100% specificity of the assay. In conclusion, we proved the reliability of archived brain homogenates and post-mortem CSF samples for retrospective analysis by RT-QuIC after long-term storage, without changed reactivity.

Download Full-text

Sporadic Creutzfeldt-Jakob Disease in a Very Young Person

Neurology ◽

10.1212/wnl.0000000000012737 ◽

2021 ◽

pp. 10.1212/WNL.0000000000012737

Author(s):

Brian Stephen Appleby ◽

Ryan Maddox ◽

Lawrence B. Schonberger ◽

ignazio cali ◽

Teresa Hammett ◽

...

Keyword(s):

Risk Factors ◽

Prion Disease ◽

Psychiatric Symptoms ◽

Disease Risk ◽

Brain Magnetic Resonance Imaging ◽

Final Diagnosis ◽

Genetic Mutation ◽

Post Mortem ◽

Post Mortem Examination ◽

Jakob Disease

Objectives:Sporadic Creutzfeldt-Jakob disease (sCJD) is the most common form of human prion disease and typically occurs in mid-to-late life. sCJD in early adulthood is extremely uncommon. The purpose of this report is to raise awareness of young cases of sCJD that are not associated with a genetic mutation or acquired prion disease risk factors.Methods:We describe the clinical presentation, diagnostic work-up, and post-mortem examination of a 22-year-old man with sCJD.Results:The patient presented with a rapidly progressive neurocognitive disorder consisting of early and prominent psychiatric symptoms. Cerebrospinal (CSF) real time quaking induced conversion (RT-QuIC) was indeterminate, and brain magnetic resonance imaging (MRI) was suggestive of prion disease. Neuropathologic examination and the absence of a genetic mutation and acquired prion disease risk factors resulted in a final diagnosis of sCJD.Discussion:Although extremely rare, sCJD can occur in young people and should be considered in the setting of rapidly progressive neuropsychiatric conditions. Post-mortem examination is required to diagnose the type of prion disease and remains important to surveil for known and potentially novel acquired prion diseases.

Download Full-text

Feasibility of Remote Assessment of Human Prion Diseases for Research and Surveillance

Dementia and Geriatric Cognitive Disorders ◽

10.1159/000497055 ◽

2019 ◽

Vol 47 (1-2) ◽

pp. 79-90

Author(s):

Brian S. Appleby ◽

Kathleen Glisic ◽

Daniel D. Rhoads ◽

Alberto Bizzi ◽

Mark L. Cohen ◽

...

Keyword(s):

Medical Record ◽

Prion Disease ◽

Prion Diseases ◽

Neuropsychiatric Symptoms ◽

Medical Record Review ◽

Rapid Progression ◽

Geographic Dispersion ◽

Disease Research ◽

Remote Assessment ◽

Record Review

Background: Prion disease research and surveillance can be challenging due to the disease’s difficulty to diagnose, rapid progression, and geographic dispersion. Improving accessibility through teleneurology could improve the ability to conduct these activities. Objectives: The aim of this study was to determine the feasibility of conducting teleneurology assessments for research and surveillance of prion diseases. Method: Participants were offered in-person visit, medical record review, or teleneurology assessment. Standardized histories and assessments evaluating cognition, functional ability, and neuropsychiatric symptoms were collected. Data regarding participants’ satisfaction with teleneurology were collected. Results: From April 2017 to July 2018, the study received 114 referrals. 45 and 5 participants consented for the teleneurology and medical record review arms of the study, respectively. 29 subjects participated in at least one teleneurology visit. Participants expressed satisfaction with teleneurology and found it easy to participate. Some aspects of the examination were hindered or interrupted due to technological reasons. Conclusions: We demonstrate the feasibility and preference of teleneurology as a modality in which subjects with prion disease can partake in clinical research. Technological aspects sometimes interfered with research assessments.

Download Full-text

Preparation And elemental analysis of ancient fibers

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100126846 ◽

1987 ◽

Vol 45 ◽

pp. 410-411

Author(s):

Allen Angel ◽

Kathryn A. Jakes

Keyword(s):

Cross Sections ◽

Physical Structure ◽

Energy Dispersive ◽

Archaeological Sites ◽

X Ray ◽

Long Term Storage ◽

Backscattered Electron ◽

Electron Imaging

Fabrics recovered from archaeological sites often are so badly degraded that fiber identification based on physical morphology is difficult. Although diagenetic changes may be viewed as destructive to factors necessary for the discernment of fiber information, changes occurring during any stage of a fiber's lifetime leave a record within the fiber's chemical and physical structure. These alterations may offer valuable clues to understanding the conditions of the fiber's growth, fiber preparation and fabric processing technology and conditions of burial or long term storage (1).Energy dispersive spectrometry has been reported to be suitable for determination of mordant treatment on historic fibers (2,3) and has been used to characterize metal wrapping of combination yarns (4,5). In this study, a technique is developed which provides fractured cross sections of fibers for x-ray analysis and elemental mapping. In addition, backscattered electron imaging (BSI) and energy dispersive x-ray microanalysis (EDS) are utilized to correlate elements to their distribution in fibers.

Download Full-text

Long-term outcomes of medical therapy in patients with acromegaly: a retrospective analysis

Endocrine Abstracts ◽

10.1530/endoabs.49.ep947 ◽

2017 ◽

Author(s):

Iulia Simona Soare ◽

Minodora Andreea Betivoiu ◽

Sorina Carmen Martin ◽

Anca Elena Sirbu ◽

Carmen Gabriela Barbu ◽

...

Keyword(s):

Retrospective Analysis ◽

Medical Therapy ◽

Long Term Outcomes

Download Full-text

Modelling of Moisture Movement in Wood during Outdoor Storage

Nonlinear Analysis Modelling and Control ◽

10.15388/na.2001.6.1.15210 ◽

2001 ◽

Vol 6 (2) ◽

pp. 3-14 ◽

Cited By ~ 23

Author(s):

R. Baronas ◽

F. Ivanauskas ◽

I. Juodeikienė ◽

A. Kajalavičius

Keyword(s):

Experimental Data ◽

Finite Difference ◽

Climatic Conditions ◽

Two Dimensional ◽

Moisture Movement ◽

Finite Difference Technique ◽

Long Term Storage ◽

Space Formulation ◽

Term Storage

A model of moisture movement in wood is presented in this paper in a two-dimensional-in-space formulation. The finite-difference technique has been used in order to obtain the solution of the problem. The model was applied to predict the moisture content in sawn boards from pine during long term storage under outdoor climatic conditions. The satisfactory agreement between the numerical solution and experimental data was obtained.

Download Full-text