Long-term potentiation-like plasticity is retained during relapse in patients with Multiple Sclerosis.

Objective: To investigate the degree of synaptic plasticity in Multiple Sclerosis (MS) patients during acute relapses compared to stable MS patients and healthy controls (HCs) and to analyze its functional relevance.
Methods: Facilitatory quadripulse stimulation (QPS) was applied to the primary motor cortex in 18 acute relapsing and 18 stable MS patients, as well as 18 HCs. The degree of synaptic plasticity was measured by the change in motor evoked potential amplitude following QPS. Symptom recovery was assessed three months after relapse.
Results: Synaptic plasticity was induced in all groups. The degree of induced plasticity did not differ between acute relapsing patients, HCs, and stable MS patients. Plasticity was significantly higher in relapsing patients with motor disability compared to relapsing patients without motor disability. In most patients (n = 9, 50%) symptoms had at least partially recovered three months after the relapse, impeding meaningful analysis of the functional relevance of baseline synaptic plasticity.
Conclusions: QPS-induced synaptic plasticity is retained during acute MS relapses. Subgroup analyses suggest that stabilizing metaplastic mechanisms may be more important to prevent motor disability but its functional relevance needs to be verified in larger, longitudinal studies.
Significance: New insights into synaptic plasticity during MS relapses are provided.
Competing Interests: Conflict of Interest Statement C. Balloff reports no disclosures relevant to the manuscript. S. Novello reports no disclosures relevant to the manuscript. A-S. Stucke reports no disclosures relevant to the manuscript. L.K. Janssen has received an individual funding granted by the Research Committee of the Medical Faculty of the Heinrich Heine University Düsseldorf for her doctoral thesis (October 2021 - March 2022). E. Heinen reports no disclosures relevant to the manuscript. C.J. Hartmann reports no disclosures relevant to the manuscript. S.G. Meuth has received honoraria for lecturing and travel expenses for attending meetings from Almirall, Amicus Therapeutics Germany, Bayer Health Care, Biogen, Celgene, Diamed, Genzyme, MedDay Pharmaceuticals, Merck Serono, Novartis, Novo Nordisk, ONO Pharma, Roche, SanofiAventis, Chugai Pharma, QuintilesIMS and Teva, and research funding from the German Ministry for Education and Research (BMBF), the Deutsche Forschungsgemeinschaft, the Else Kröner Fresenius Foundation, the German Academic Exchange Service, the Hertie Foundation, the Interdisciplinary Center for Clinical Studies (IZKF) Muenster, the German Foundation for Neurology, Almirall, Amicus Therapeutics, Germany, Biogen, Diamed, Fresenius Medical Care, Genzyme, Merck Serono, Novartis, ONO Pharma, Roche and Teva. A. Schnitzler has received lecture fees from Abbott, Novartis, Kyowa Kirin, and has been serving as a consultant for Abbott, Zambon, Medtronic Inc. He received royalties from the Georg Thieme Verlag. He is a government employee and receives through his institution funding for his research from the German Research Council, Abbott, and the Brunhilde Moll Foundation. I.-K. Penner received honoraria for speaking at scientific meetings, serving at scientific advisory boards and consulting activities from Adamas Pharma, Almirall, Bayer Pharma, Biogen, BMS, Celgene, Sanofi-Genzyme, Janssen, Merck, Novartis, Roche, and Teva. She received research support from the German MS Society, Celgene, Novartis, Roche, and Teva. S.J. Groiss received honoraria and/or travel expenses from Abbott Medical, Abbvie, Bial, Boston Scientific, Inomed, Medtronic, Rogue Research, UCB, consulting fees from Bial, Zambon and research support from Abbott and Hilde-Ulrichs Stiftung. P. Albrecht received compensation for serving on Scientific Advisory Boards for Allergan, Celgene, Janssen Cilag, Ipsen, Merck, Merz Pharmaceuticals, Novartis, Biogen; he received speaker honoraria and travel support from Novartis, Teva, Biogen, Celgene, Merz Pharmaceuticals, Ipsen, Allergan, Bayer Healthcare, Esai, UCB; Roche; he received research support from Novartis, Allergan, Biogen, Celgene, Teva, Merz Pharmaceuticals, Ipsen, and Roche.
(Copyright © 2023 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)