Acute and chronic synaptic pathology in multiple sclerosis gray matter

2021 ◽  
pp. 135245852110221
Author(s):  
Marco Vercellino ◽  
Stella Marasciulo ◽  
Silvia Grifoni ◽  
Elena Vallino-Costassa ◽  
Chiara Bosa ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Brain Tissue ◽  
Gray Matter ◽  
Axonal Loss ◽  
Strong Indication ◽  
Synaptic Loss ◽  
Synaptic Density ◽  
Synaptic Pathology ◽  
Gabaergic Synapses ◽  
And Control

Objectives: To investigate the extent of synaptic loss, and the contribution of gray matter (GM) inflammation and demyelination to synaptic loss, in multiple sclerosis (MS) brain tissue. Methods: This study was performed on two different post-mortem series of MS and control brains, including deep GM and cortical GM. MS brain samples had been specifically selected for the presence of active demyelinating GM lesions. Over 1,000,000 individual synapses were identified and counted using confocal microscopy, and further characterized as glutamatergic/GABAergic. Synaptic counts were also correlated with neuronal/axonal loss. Results: Important synaptic loss was observed in active demyelinating GM lesions (−58.9%), while in chronic inactive GM lesions, synaptic density was only mildly reduced compared to adjacent non-lesional gray matter (NLGM) (−12.6%). Synaptic loss equally affected glutamatergic and GABAergic synapses. Diffuse synaptic loss was observed in MS NLGM compared to control GM (−21.2% overall). Conclusion: This study provides evidence, in MS brain tissue, of acute synaptic damage/loss during active GM inflammatory demyelination and of synaptic reorganization in chronically demyelinated GM, affecting equally glutamatergic and GABAergic synapses. Furthermore, this study provides a strong indication of widespread synaptic loss in MS NLGM also independently from focal GM demyelination.

scholarly journals Neuronal and Axonal Loss in Normal-Appearing Gray Matter and Subpial Lesions in Multiple Sclerosis

2015 ◽  
Vol 74 (5) ◽  
pp. 453-458 ◽  
Author(s):  
Roel Klaver ◽  
Veronica Popescu ◽  
Pieter Voorn ◽  
Yvonne Galis-de Graaf ◽  
Paul van der Valk ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Gray Matter ◽  
Axonal Loss

scholarly journals Synaptic Loss in Multiple Sclerosis: A Systematic Review of Human Post-mortem Studies

2021 ◽  
Vol 12 ◽  
Author(s):  
E. E. Amelie Möck ◽  
Eveliina Honkonen ◽  
Laura Airas
Keyword(s):  
Multiple Sclerosis ◽  
Systematic Review ◽  
Post Mortem ◽  
Reference Tissue ◽  
Synaptic Loss ◽  
Synaptic Density ◽  
Density Measurements ◽  
Entire Central Nervous System ◽  
Selection Of

Background: Gray matter pathology plays a central role in the progression of multiple sclerosis (MS). The occurrence of synaptic loss appears to be important but, to date, still poorly investigated aspect of MS pathology. In this systematic review, we drew from the recent knowledge about synaptic loss in human post-mortem studies.Methods: We conducted a systematic search with PubMed to identify relevant publications. Publications available from15 June 2021 were taken into account. We selected human post-mortem studies that quantitatively assessed the synapse number in MS tissue.Results: We identified 14 relevant publications out of which 9 reported synaptic loss in at least one investigated subregion. The most commonly used synaptic marker was synaptophysin; non-etheless, we found substantial differences in the methodology and the selection of reference tissue. Investigated regions included the cortex, the hippocampus, the cerebellum, the thalamus, and the spinal cord.Conclusion: Synaptic loss seems to take place throughout the entire central nervous system. However, the results are inconsistent, probably due to differences in the methodology. Moreover, synaptic loss appears to be a dynamic process, and thus the nature of this pathology might be captured using in vivo synaptic density measurements.

Mild gray matter atrophy in patients with long-standing multiple sclerosis and favorable clinical course

2021 ◽  
pp. 135245852110196
Author(s):  
Rosa Cortese ◽  
Marco Battaglini ◽  
Francesca Parodi ◽  
Maria Laura Stromillo ◽  
Emilio Portaccio ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Gray Matter ◽  
Clinical Course ◽  
Resonance Imaging ◽  
Volume Changes ◽  
Magnetic Resonance Imaging Mri ◽  
Global Brain ◽  
Diffuse Brain

The mechanisms responsible for the favorable clinical course in multiple sclerosis (MS) remain unclear. In this longitudinal study, we assessed whether magnetic resonance imaging (MRI)-based changes in focal and diffuse brain damage are associated with a long-term favorable MS diseases course. We found that global brain and gray matter (GM) atrophy changes were milder in MS patients with long-standing disease (⩾30 years from onset) and favorable (no/minimal disability) clinical course than in sex-age-matched disable MS patients, independently of lesions accumulation. Data showed that different trajectories of volume changes, as reflected by mild GM atrophy, may characterize patients with long-term favorable evolution.

scholarly journals Views of the Future of Partners of People with Multiple Sclerosis Who Attended a Lifestyle Modification Workshop: A Qualitative Analysis of Perspectives and Experiences

2020 ◽  
Vol 18 (1) ◽  
pp. 85
Author(s):  
Sandra L. Neate ◽  
Keryn L. Taylor ◽  
Nupur Nag ◽  
George A. Jelinek ◽  
Steve Simpson-Yap ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Health Outcomes ◽  
Lifestyle Modification ◽  
Structured Interviews ◽  
Interpretive Phenomenology ◽  
Related Risk ◽  
The Future ◽  
Partner Perceptions ◽  
And Control ◽  
The Impact

People with multiple sclerosis (PwMS) often experience uncertainty and fear about their futures. Partners of PwMS may share their concerns and experience fears about their own futures, limitations on their lives, ability to work, and becoming a carer. For PwMS, modification of lifestyle-related risk factors has been associated with improved health outcomes. For PwMS who attended residential lifestyle modification workshops (RLMW), sustained improved health outcomes have been demonstrated. Whether improved outcomes for PwMS who engage with lifestyle modification translate to improved partner perceptions of the future, is yet to be explored. We explored the perspectives of partners of PwMS who had attended a RLMW and the impact that the person with MS’s illness and their engagement with lifestyle modification had on their partners’ views of the future. Analysis of 21 semi-structured interviews used a methodology informed by Heidegger’s Interpretive Phenomenology. Three themes emerged: ‘uncertainty’, ‘planning for the future’ and ‘control, empowerment and confidence’. Subthemes included MS and lifestyle modification being a catalyst for positive change; developing a sense of control and empowerment; and hope, optimism and positivity. Lifestyle modification may provide benefits, not only to PwMS, but also to their partners, and should be considered part of mainstream management of MS.

Characterization of multiple sclerosis neuroinflammation and neurodegeneration with relaxation and diffusion basis spectrum imaging

2021 ◽  
pp. 135245852110233
Author(s):  
Irene M Vavasour ◽  
Peng Sun ◽  
Carina Graf ◽  
Jackie T Yik ◽  
Shannon H Kolind ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Specific Information ◽  
Axonal Loss ◽  
Normal Appearing White Matter ◽  
Relapsing Remitting ◽  
Tissue Changes ◽  
Spectrum Imaging ◽  
Magnetic Resonance Imaging Mri ◽  
And Diffusion

Background: Advanced magnetic resonance imaging (MRI) methods can provide more specific information about various microstructural tissue changes in multiple sclerosis (MS) brain. Quantitative measurement of T1 and T2 relaxation, and diffusion basis spectrum imaging (DBSI) yield metrics related to the pathology of neuroinflammation and neurodegeneration that occurs across the spectrum of MS. Objective: To use relaxation and DBSI MRI metrics to describe measures of neuroinflammation, myelin and axons in different MS subtypes. Methods: 103 participants (20 clinically isolated syndrome (CIS), 33 relapsing-remitting MS (RRMS), 30 secondary progressive MS and 20 primary progressive MS) underwent quantitative T1, T2, DBSI and conventional 3T MRI. Whole brain, normal-appearing white matter, lesion and corpus callosum MRI metrics were compared across MS subtypes. Results: A gradation of MRI metric values was seen from CIS to RRMS to progressive MS. RRMS demonstrated large oedema-related differences, while progressive MS had the most extensive abnormalities in myelin and axonal measures. Conclusion: Relaxation and DBSI-derived MRI measures show differences between MS subtypes related to the severity and composition of underlying tissue damage. RRMS showed oedema, demyelination and axonal loss compared with CIS. Progressive MS had even more evidence of increased oedema, demyelination and axonal loss compared with CIS and RRMS.

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