
Contributions
Abstract: 221
Type: Oral
Abstract Category: Pathology and pathogenesis of MS - Progressive MS
Background: Clinically, chronic MS often resembles progressive myelopathy. In addition to the spinal cord axons and anterior horn cells lost in the course of MS, the network organisation of the spinal cord suggests further pathologic mechanisms may be driving chronic disability. Spinal cord grey matter pathology has been identified as an important contributor to this dysfunction; however analysis of synaptic connectivity has never been undertaken.
Objectives: To quantify the extent of synaptic loss in post mortem MS spinal cord and assess its relationship with grey matter area and demyelination.
Methods: Formalin fixed spinal cords of 12 people with MS (pwMS) and four controls were studied. 10µm-thick sections were obtained from two each of cervical, thoracic and lumbar blocks, and stained for synaptophysin and myelin basic protein. Synaptophysin intensity was quantified and the area of synaptic boutons measured around 5 neurons in each anterior GM horn. Non-parametric tests and Spearman Rank correlation were used for analysis.
Results: Synaptophysin was reduced by 56% and 62% (p< 0.0001) in non-lesional GM (NLGM) and GM lesions (GML), respectively (14% lower in GML compared to NAGM [p= 0.03]). The area of synaptic boutons was 92% and 96% (p< 0.0001) smaller in NAGM and GML, respectively. Further, we found reduction by 47% of the synaptic bouton area in GML compared to NAGM (p< 0.0001). Correlation was detected between (i) synaptic bouton area and (ii) anterior GM horn area (r= 0.42, p< 0.0001) and (iii) demyelination (p= -0.42, p< 0.0001).
Conclusions: The extent of synaptic loss in the chronic MS spinal cord is striking and affects both NLGM as well as GML. Whether synapses are lost as a result of axonal injury only or through different/additional mechanisms is unknown. Further work will focus on the relationship between synaptic loss, neuronal injury, and the association between synaptic pathology and clinical information.
Disclosure: Natalia Petrova: nothing to disclose. Daniele Carassiti: nothing to disclose. Francesco Scaravilli: nothing to disclose. David Baker has received research support from Sanofi-Genzyme and a founder, shareholder and consultant to Canbex Therapeutics.
Klaus Schmierer : PI of trials sponsored by Novartis, Roche & Teva. He is involved in trials sponsored by Biogen, Genzyme, BIAL, Cytokinetics, Canbex. Speaking honoraria from, and/or served in an advisory role for, Biogen, Novartis, Teva, Merck Inc. Supported by Genzyme to attend AAN 2014. Supported by Novartis to attend AAN 2016. Research support from Novartis, Biogen, National MS Society (US), MS Society of Great Britain & Northern Ireland, Royal College of Radiologists, and Barts Charity.
Abstract: 221
Type: Oral
Abstract Category: Pathology and pathogenesis of MS - Progressive MS
Background: Clinically, chronic MS often resembles progressive myelopathy. In addition to the spinal cord axons and anterior horn cells lost in the course of MS, the network organisation of the spinal cord suggests further pathologic mechanisms may be driving chronic disability. Spinal cord grey matter pathology has been identified as an important contributor to this dysfunction; however analysis of synaptic connectivity has never been undertaken.
Objectives: To quantify the extent of synaptic loss in post mortem MS spinal cord and assess its relationship with grey matter area and demyelination.
Methods: Formalin fixed spinal cords of 12 people with MS (pwMS) and four controls were studied. 10µm-thick sections were obtained from two each of cervical, thoracic and lumbar blocks, and stained for synaptophysin and myelin basic protein. Synaptophysin intensity was quantified and the area of synaptic boutons measured around 5 neurons in each anterior GM horn. Non-parametric tests and Spearman Rank correlation were used for analysis.
Results: Synaptophysin was reduced by 56% and 62% (p< 0.0001) in non-lesional GM (NLGM) and GM lesions (GML), respectively (14% lower in GML compared to NAGM [p= 0.03]). The area of synaptic boutons was 92% and 96% (p< 0.0001) smaller in NAGM and GML, respectively. Further, we found reduction by 47% of the synaptic bouton area in GML compared to NAGM (p< 0.0001). Correlation was detected between (i) synaptic bouton area and (ii) anterior GM horn area (r= 0.42, p< 0.0001) and (iii) demyelination (p= -0.42, p< 0.0001).
Conclusions: The extent of synaptic loss in the chronic MS spinal cord is striking and affects both NLGM as well as GML. Whether synapses are lost as a result of axonal injury only or through different/additional mechanisms is unknown. Further work will focus on the relationship between synaptic loss, neuronal injury, and the association between synaptic pathology and clinical information.
Disclosure: Natalia Petrova: nothing to disclose. Daniele Carassiti: nothing to disclose. Francesco Scaravilli: nothing to disclose. David Baker has received research support from Sanofi-Genzyme and a founder, shareholder and consultant to Canbex Therapeutics.
Klaus Schmierer : PI of trials sponsored by Novartis, Roche & Teva. He is involved in trials sponsored by Biogen, Genzyme, BIAL, Cytokinetics, Canbex. Speaking honoraria from, and/or served in an advisory role for, Biogen, Novartis, Teva, Merck Inc. Supported by Genzyme to attend AAN 2014. Supported by Novartis to attend AAN 2016. Research support from Novartis, Biogen, National MS Society (US), MS Society of Great Britain & Northern Ireland, Royal College of Radiologists, and Barts Charity.