Cytoskeleton-Associated Risk Modifiers Involved in Early and Rapid Progression of Sporadic Creutzfeldt-Jakob Disease

Creutzfeldt-Jakob disease (CJD) is a rapidly progressive, fatal neurodegenerative disorder belonging to the family of transmissible spongiform encephalopathies. The disease is believed to be caused by an abnormal isoform of a cellular glycoprotein known as the prion protein. Our patient is an 84-year-old Caucasian man who presented to the geriatric clinic for evaluation of short-term memory loss and decreased concentration which started 3 months prior to initial evaluation. Rapid progression of dementia demonstrated by severe impairment in tasks with a predominantly visual component, including visual scanning, perceptual reasoning and visual spatial processing. Diagnosis of CJD was determined by characteristic ribboning on brain MRI as well as notable real-time quaking-induced conversion on cerebrospinal fluid.

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Current Nosology of Neural Autoantibody-Associated Dementia

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.711195 ◽

2021 ◽

Vol 13 ◽

Author(s):

Niels Hansen

Keyword(s):

Basic Protein ◽

Clinical Presentation ◽

Lewy Bodies ◽

Rapid Progression ◽

Aspartate Receptor ◽

Atypical Clinical Presentation ◽

Neurodegenerative Dementia ◽

Memory Clinics ◽

Jakob Disease ◽

Receptor Antibodies

BackgroundThe detection of neural autoantibodies in patients with cognitive decline is an increasingly frequent phenomenon in memory clinics, and demanding as it does a specific diagnostic approach and therapeutic management, it deserves greater attention. It is this review’s aim to present the latest nosology of neural autoantibody-associated dementia.MethodsA specific literature research via PubMed was conducted to describe the nosology of neural autoantibody-associated dementia.ResultsAn autoimmune dementia comprises with an early onset, atypical clinical presentation and rapid progression in conjunction with neural antibodies, signs of inflammation in the cerebrospinal fluid, and a non-neurodegenerative pattern in neuroimaging. An autoimmune dementia is probably present if the patient responds to immunotherapy. Atypical dementia involving neural autoantibodies with mostly N-methyl-D-aspartate receptor antibodies might not fulfill all the autoimmune-dementia criteria, thus it may constitute an independent disease entity. Finally, a neurodegenerative dementia such as the frontotemporal type also coincides with neural autoantibodies such as the subunit ionotropic glutamate receptors 3 of amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antibodies, dementia with Lewy bodies with myelin oligodendrocytic protein, myelin basic protein antibodies, or Creutzfeldt-Jakob disease with Zic4 or voltage gated potassium channel antibodies. These dementia entities may well overlap in their clinical features and biomarkers, i.e., their neural autoantibodies or neuroimaging patterns.ConclusionThere are three main forms of neural autoantibody-associated dementia we can distinguish that might also share certain features in their clinical and laboratory presentation. More research is urgently necessary to improve the diagnosis and therapy of these patients, as the progression of their dementia might thus be improved or even reversed.

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Pearls & Oy-sters: Typical Atypical Creutzfeld-Jakob Disease: A Case Presenting as a Rapidly Progressive Corticobasal Syndrome Without Dementia

Neurology ◽

10.1212/wnl.0000000000012613 ◽

2021 ◽

pp. 10.1212/WNL.0000000000012613

Author(s):

Zoe Olga Marinides ◽

Timothy R Malone ◽

Yitao Ma ◽

Jason Hawley

Keyword(s):

Diagnostic Testing ◽

Behavioral Changes ◽

Corticobasal Syndrome ◽

Rapid Progression ◽

Early Disease ◽

Early Dementia ◽

Progressive Neurodegeneration ◽

Characteristic Imaging ◽

Jakob Disease ◽

High Index Of Suspicion

Creutzfeld-Jakob Disease (CJD) is a rare disease but a common cause of rapidly progressive neurodegeneration. Although the “classic” presentation involves early dementia or behavioral changes, there are well-described atypical variants with less prominent cognitive symptoms at onset. One such variant is Corticobasal Syndrome (CBS), which may be seen with other underlying neurodegenerative processes, but when due to prion disease pathology involves much more rapid progression and certain characteristic imaging findings. This report presents a case presenting as CBS without cognitive or behavioral changes at onset, which rapidly progressed and was determined ultimately to be due to underlying CJD. This case illustrates the need for a high index of suspicion for CJD in order to drive appropriate diagnostic testing and careful review of imaging and EEG findings, which may be subtle in early disease.

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Functional Magnetic Resonance Imaging in the Final Stage of Creutzfeldt-Jakob Disease

Diagnostics ◽

10.3390/diagnostics10050309 ◽

2020 ◽

Vol 10 (5) ◽

pp. 309

Author(s):

Stefan M. Golaszewski ◽

Bettina Wutzl ◽

Axel F. Unterrainer ◽

Cristina Florea ◽

Kerstin Schwenker ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Functional Magnetic Resonance Imaging ◽

Vegetative State ◽

Rapid Progression ◽

Functional Magnetic Resonance ◽

Resonance Imaging ◽

Apallic Syndrome ◽

Jakob Disease ◽

The Central Nervous System

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare fatal degenerative disease of the central nervous system. The clinical course is characterized by rapid progression of neurological and neuromuscular symptoms. The late stage with loss of consciousness is not well characterized. We report a 62-year-old male patient with sCJD with the clinical picture of a vegetative state/apallic syndrome, in whom we studied cortical responses using a vibration paradigm. The functional magnetic resonance imaging (fMRI) investigation demonstrated a clear response within the sensorimotor cortex, the cerebellum, the parietal cortex, the insular, and frontal inferior region. The finding of persistent cortical activity on fMRI in a patient with CJD in a state of unconsciousness has implications for the clinical management and for ethical considerations.

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RNA editing alterations define manifestation of prion diseases

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1803521116 ◽

2019 ◽

Vol 116 (39) ◽

pp. 19727-19735 ◽

Cited By ~ 5

Author(s):

Eirini Kanata ◽

Franc Llorens ◽

Dimitra Dafou ◽

Athanasios Dimitriadis ◽

Katrin Thüne ◽

...

Keyword(s):

Disease Progression ◽

Rna Editing ◽

Prion Disease ◽

Prion Diseases ◽

Rapid Progression ◽

Human Prion Disease ◽

Progressive Dementia ◽

Molecular Alterations ◽

Jakob Disease ◽

Subtype A

Prion diseases are fatal neurodegenerative disorders caused by misfolding of the normal prion protein into an infectious cellular pathogen. Clinically characterized by rapidly progressive dementia and accounting for 85% of human prion disease cases, sporadic Creutzfeldt–Jakob disease (sCJD) is the prevalent human prion disease. Although sCJD neuropathological hallmarks are well-known, associated molecular alterations are elusive due to rapid progression and absence of preclinical stages. To investigate transcriptome alterations during disease progression, we utilized tg340-PRNP129MM mice infected with postmortem material from sCJD patients of the most susceptible genotype (MM1 subtype), a sCJD model that faithfully recapitulates the molecular and pathological alterations of the human disease. Here we report that transcriptomic analyses from brain cortex in the context of disease progression, reveal epitranscriptomic alterations (specifically altered RNA edited pathway profiles, eg., ER stress, lysosome) that are characteristic and possibly protective mainly for preclinical and clinical disease stages. Our results implicate regulatory epitranscriptomic mechanisms in prion disease neuropathogenesis, whereby RNA-editing targets in a humanized sCJD mouse model were confirmed in pathological human autopsy material.

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