scholarly journals Histotype-Dependent Oligodendroglial PrP Pathology in Sporadic CJD: A Frequent Feature of the M2C “Strain”

Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1796
Author(s):  
Ellen Gelpi ◽  
Sigrid Klotz ◽  
Nuria Vidal-Robau ◽  
Gerda Ricken ◽  
Günther Regelsberger ◽  
...  
Keyword(s):  
White Matter ◽  
Grey Matter ◽  
Disease Duration ◽  
Molecular Subtypes ◽  
Deposition Pattern ◽  
Jakob Disease ◽  
Sporadic Cjd

In sporadic Creutzfeldt-Jakob disease, molecular subtypes are neuropathologically well identified by the lesioning profile and the immunohistochemical PrPd deposition pattern in the grey matter (histotypes). While astrocytic PrP pathology has been reported in variant CJD and some less frequent histotypes (e.g., MV2K), oligodendroglial pathology has been rarely addressed. We assessed a series of sCJD cases with the aim to identify particular histotypes that could be more prone to harbor oligodendroglial PrPd. Particularly, the MM2C phenotype, in both its more “pure” and its mixed MM1+2C or MV2K+2C forms, showed more frequent oligodendroglial PrP pathology in the underlying white matter than the more common MM1/MV1 and VV2 histotypes, and was more abundant in patients with a longer disease duration. We concluded that the MM2C strain was particularly prone to accumulate PrPd in white matter oligodendrocytes.

scholarly journals A voxel-based morphometry study of disease severity correlates in relapsing— remitting multiple sclerosis

2009 ◽  
Vol 16 (1) ◽  
pp. 45-54 ◽  
Author(s):  
A. Prinster ◽  
M. Quarantelli ◽  
R. Lanzillo ◽  
G. Orefice ◽  
G. Vacca ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Grey Matter ◽  
Disease Duration ◽  
Expanded Disability Status Scale ◽  
Lesion Load ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Previous studies have shown a preferential loss of grey matter in fronto-temporal regions in patients with multiple sclerosis. Studies of correlates of disease severity are more controversial, because some studies have suggested an association between sensorimotor cortex atrophy and Expanded Disability Status Scale score, while others did not find such a correlation. The objective of this study was to assess the correlation of regional loss of grey matter and white matter with indexes of clinical and radiological severity in relapsing—remitting multiple sclerosis, including the Expanded Disability Status Scale and lesion load. Correlations between Expanded Disability Status Scale, lesion load and disease duration were assessed in 128 patients with relapsing—remitting multiple sclerosis (Expanded Disability Status Scale range 1.0—6.0) using optimized voxel-based morphometry. Bilateral loss of grey matter in sensorimotor cortices was correlated with Expanded Disability Status Scale, and tissue loss also involved adjacent white matter, extending along pyramidal tracts to the brainstem. Increasing lesion load was correlated with loss of deep grey matter and white matter. No specific region of grey matter or white matter showed a significant correlation with disease duration. These findings support the hypothesis that motor neuron involvement plays a major role in the progression of physical disability. Lesion load accrual affects mainly highly interconnected subcortical structures, while disease duration has a less significant impact on brain atrophy, probably owing to the inter-subject heterogeneity of the clinical course of the disease.

Individual differences in white and grey matter structure associated with verbal habits of thought

2019 ◽  
Author(s):  
Justin C. Hayes ◽  
Katherine L Alfred ◽  
Rachel Pizzie ◽  
Joshua S. Cetron ◽  
David J. M. Kraemer
Keyword(s):  
Individual Differences ◽  
White Matter ◽  
Cognitive Processing ◽  
Grey Matter ◽  
Structural Changes ◽  
Structural Integrity ◽  
Diffusion Tensor ◽  
Self Report ◽  
White Matter Tracts

Modality specific encoding habits account for a significant portion of individual differences reflected in functional activation during cognitive processing. Yet, little is known about how these habits of thought influence long-term structural changes in the brain. Traditionally, habits of thought have been assessed using self-report questionnaires such as the visualizer-verbalizer questionnaire. Here, rather than relying on subjective reports, we measured habits of thought using a novel behavioral task assessing attentional biases toward picture and word stimuli. Hypothesizing that verbal habits of thought are reflected in the structural integrity of white matter tracts and cortical regions of interest, we used diffusion tensor imaging and volumetric analyses to assess this prediction. Using a whole-brain approach, we show that word bias is associated with increased volume in several bilateral language regions, in both white and grey matter parcels. Additionally, connectivity within white matter tracts within an a priori speech production network increased as a function of word bias. These results demonstrate long-term structural and morphological differences associated with verbal habits of thought.

scholarly journals Modelling the cascade of biomarker changes in GRN-related frontotemporal dementia

2021 ◽  
pp. jnnp-2020-323541
Author(s):  
Jessica L Panman ◽  
Vikram Venkatraghavan ◽  
Emma L van der Ende ◽  
Rebecca M E Steketee ◽  
Lize C Jiskoot ◽  
...  
Keyword(s):  
White Matter ◽  
Frontotemporal Dementia ◽  
Disease Severity ◽  
Grey Matter ◽  
Clinical Stage ◽  
Data Driven ◽  
Grey Matter Volume ◽  
Matter Volume ◽  
Mutation Carriers ◽  
Individual Disease

ObjectiveProgranulin-related frontotemporal dementia (FTD-GRN) is a fast progressive disease. Modelling the cascade of multimodal biomarker changes aids in understanding the aetiology of this disease and enables monitoring of individual mutation carriers. In this cross-sectional study, we estimated the temporal cascade of biomarker changes for FTD-GRN, in a data-driven way.MethodsWe included 56 presymptomatic and 35 symptomatic GRN mutation carriers, and 35 healthy non-carriers. Selected biomarkers were neurofilament light chain (NfL), grey matter volume, white matter microstructure and cognitive domains. We used discriminative event-based modelling to infer the cascade of biomarker changes in FTD-GRN and estimated individual disease severity through cross-validation. We derived the biomarker cascades in non-fluent variant primary progressive aphasia (nfvPPA) and behavioural variant FTD (bvFTD) to understand the differences between these phenotypes.ResultsLanguage functioning and NfL were the earliest abnormal biomarkers in FTD-GRN. White matter tracts were affected before grey matter volume, and the left hemisphere degenerated before the right. Based on individual disease severities, presymptomatic carriers could be delineated from symptomatic carriers with a sensitivity of 100% and specificity of 96.1%. The estimated disease severity strongly correlated with functional severity in nfvPPA, but not in bvFTD. In addition, the biomarker cascade in bvFTD showed more uncertainty than nfvPPA.ConclusionDegeneration of axons and language deficits are indicated to be the earliest biomarkers in FTD-GRN, with bvFTD being more heterogeneous in disease progression than nfvPPA. Our data-driven model could help identify presymptomatic GRN mutation carriers at risk of conversion to the clinical stage.

The Three Glycotypes in the London Classification System of Sporadic Creutzfeldt-Jakob Disease Differ in Disease Duration

2021 ◽  
Author(s):  
Blair Ney ◽  
Dhamidhu Eratne ◽  
Victoria Lewis ◽  
Luke Ney ◽  
Qiao-Xin Li ◽  
...  
Keyword(s):  
Classification System ◽  
Disease Duration ◽  
Jakob Disease

scholarly journals Atypical Creutzfeldt-Jakob Disease Evolution after Electroconvulsive Therapy for Catatonic Depression

2011 ◽  
Vol 2011 ◽  
pp. 1-3 ◽  
Author(s):  
Iria Grande ◽  
Juan Fortea ◽  
Ellen Gelpi ◽  
Itziar Flamarique ◽  
Marc Udina ◽  
...  
Keyword(s):  
Electroconvulsive Therapy ◽  
Disease Duration ◽  
Psychiatric Symptoms ◽  
Psychiatric Admission ◽  
Disease Evolution ◽  
Clinical Recovery ◽  
Jakob Disease ◽  
Magnetic Resonance Imaging Mri ◽  
Electroencephalogram Eeg ◽  
Codon 129

We describe a case report of an 80-year-old woman who presented with symptomatology compatible with an episode of major depression with catatonia. After psychiatric admission, electroconvulsive therapy (ECT) was applied, but symptoms progressed with cognitive impairment, bradykinesia, widespread stiffness, postural tremor, and gait disturbance. After compatible magnetic resonance imaging (MRI), diffusion changes, and electroencephalogram (EEG) findings the case was reoriented to Creutzfeldt-Jakob disease (CJD). The genetic study found a methionine/valine heterozygosity at codon 129 of the prion protein gene PrPSc. On followup, a significant clinical recovery turned out. For this reason, EEG and MRI were repeated and confirmed the findings. The patient subsequently demonstrated progressive clinical deterioration and died 21 months later. The diagnosis was verified postmortem by neuropathology. The vCJD subtype MV2 is indeed characterized by early and prominent psychiatric symptoms and a prolonged disease duration however no frank clinical recovery has before been reported.

scholarly journals Prion-specific and surrogate CSF biomarkers in Creutzfeldt-Jakob disease: diagnostic accuracy in relation to molecular subtypes and analysis of neuropathological correlates of p-tau and Aβ42 levels

2017 ◽  
Vol 133 (4) ◽  
pp. 559-578 ◽  
Author(s):  
Francesca Lattanzio ◽  
Samir Abu-Rumeileh ◽  
Alessia Franceschini ◽  
Hideaki Kai ◽  
Giulia Amore ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Molecular Subtypes ◽  
Csf Biomarkers ◽  
Jakob Disease

Imaging Usual Addictions: Tobacco, Canabis and Alcohol

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
C. Leroy ◽  
S. Chanraud ◽  
E. Artiges ◽  
C. Martelli ◽  
A. Cachia ◽  
...  
Keyword(s):  
White Matter ◽  
Psychosocial Functioning ◽  
Grey Matter ◽  
Diffusion Imaging ◽  
Temporal Cortex ◽  
List Type ◽  
Dopamine Level ◽  
Type Number ◽  
Positron Emission ◽  
Brain Microstructure

Background:Brain models of drug addiction are being tackled in humans, using PET and MRI.Results:1.Whereas tobacco and cannabis do not interact directly with dopamine sites, positron emission tomography detected lower availability in sites regulating the catecholamines homeostasis, notably in dopamine transporter sites in striatal and in extrastriatal regions. This further supports repeated and long term substance use progress towards an adaptative diminished basal dopamine level that would contribute to the switch to an addicted brain.2.Alcohol: abnormalities in brain macro- and micro- structure were searched in detoxified alcohol-dependents with preserved psychosocial functioning:-Brain function (fMRI): fronto-cerebellar overactivation detected during an auditory language task in alcohol-dependents may reflect the compensatory effort required for patients to maintain the same level of performance as controls.-Brain macrostructure (MRI). Widespread lower white matter volumes, and lower grey matter volumes in the frontal lobe, insula, hippocampus, thalami and cerebellum, were detected. Poorer neuropsychological performance correlated with smaller grey matter volumes in these regions and with lower white matter volume in the brainstem.-Brain microstructure (DTI): tractography of white matter fiber bundles revealed that brainstem bundles alteration may contribute to cognitive flexibility impairment. Regression analyses showed memory scores were related to brain microstructure in parahippocampal areas, frontal cortex, and left temporal cortex. This suggest diffusion imaging (DTI) is a useful probe to early alcohol-induced brain alterations.Conclusion:While indices of dopamine down-regulation are consistency detected in several drug addictions, even “socially-adapted” alcohol dependence may induce change in brain structure.Psychol Med. 1998 28:1039-48.Neuropsychopharmacology. 2007 32:429-38.IEEE Trans Med Imaging. 2007 26:553-65J Nucl Med. 2007 48:538-46.Neuropsychopharmacology (Chanraud S et al., 2008 Jul 9. [Epub ahead of print]).J Clin Psychopharmacol (Leroy C et al, in press).

Spinal cord grey matter lesions in multiple sclerosis detected by post-mortem high field MR imaging

2008 ◽  
Vol 15 (2) ◽  
pp. 180-188 ◽  
Author(s):  
CP Gilmore ◽  
JJG Geurts ◽  
N Evangelou ◽  
JCJ Bot ◽  
RA van Schijndel ◽  
...  
Keyword(s):  
Spinal Cord ◽  
White Matter ◽  
Mr Imaging ◽  
High Field ◽  
Grey Matter ◽  
Great Majority ◽  
Proton Density ◽  
Post Mortem ◽  
Mr Images ◽  
The Brain

Background Post-mortem studies demonstrate extensive grey matter demyelination in MS, both in the brain and in the spinal cord. However the clinical significance of these plaques is unclear, largely because they are grossly underestimated by MR imaging at conventional field strengths. Indeed post-mortem MR studies suggest the great majority of lesions in the cerebral cortex go undetected, even when performed at high field. Similar studies have not been performed using post-mortem spinal cord material. Aim To assess the sensitivity of high field post-mortem MRI for detecting grey matter lesions in the spinal cord in MS. Methods Autopsy material was obtained from 11 MS cases and 2 controls. Proton Density-weighted images of this formalin-fixed material were acquired at 4.7Tesla before the tissue was sectioned and stained for Myelin Basic Protein. Both the tissue sections and the MR images were scored for grey matter and white matter plaques, with the readers of the MR images being blinded to the histopathology results. Results Our results indicate that post-mortem imaging at 4.7Tesla is highly sensitive for cord lesions, detecting 87% of white matter lesions and 73% of grey matter lesions. The MR changes were highly specific for demyelination, with all lesions scored on MRI corresponding to areas of demyelination. Conclusion Our work suggests that spinal cord grey matter lesions may be detected on MRI more readily than GM lesions in the brain, making the cord a promising site to study the functional consequences of grey matter demyelination in MS.

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