Exercise training and neuroprotection in multiple sclerosis
2022; Elsevier BV; Volume: 21; Issue: 8 Linguagem: Inglês
10.1016/s1474-4422(22)00219-8
ISSN1474-4465
AutoresLars G. Hvid, Martin Langeskov‐Christensen, Egon Stenager, Ulrik Dalgas,
Tópico(s)Rheumatoid Arthritis Research and Therapies
ResumoWe read with interest the Correspondence by Brian M Sandroff and colleagues1Sandroff BM Motl RW Yong VW Cutter GR Giovannoni G Exercise training in multiple sclerosis.Lancet Neurol. 2022; 21: 313Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar on exercise training in multiple sclerosis, but believe that the rationale behind this letter could have been based on misconceptions. The authors state that two systematic reviews2Hvid LG Harwood DL Eskildsen SF Dalgas U A critical systematic review of current evidence on the effects of physical exercise on whole/regional grey matter brain volume in populations at risk of neurodegeneration.Sports Med. 2021; 51: 1651-1671Crossref PubMed Scopus (18) Google Scholar, 3Diechmann MD Campbell E Coulter E Paul L Dalgas U Hvid LG Effects of exercise training on neurotrophic factors and subsequent neuroprotection in persons with multiple sclerosis—a systematic review and meta-analysis.Brain Sci. 2021; 111499Crossref PubMed Scopus (6) Google Scholar from our research group conclude that exercise training is not associated with neuroprotection. To clarify, the first systematic review2Hvid LG Harwood DL Eskildsen SF Dalgas U A critical systematic review of current evidence on the effects of physical exercise on whole/regional grey matter brain volume in populations at risk of neurodegeneration.Sports Med. 2021; 51: 1651-1671Crossref PubMed Scopus (18) Google Scholar explicitly states that the evidence on the effects of physical exercise on brain volume in neurodegenerative populations appears sparse and inconclusive, most likely due to the absence of large, long-term (≥1 year), and well-designed studies. Moreover, the arguments put forward by Sandroff and colleagues1Sandroff BM Motl RW Yong VW Cutter GR Giovannoni G Exercise training in multiple sclerosis.Lancet Neurol. 2022; 21: 313Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar are the same as those outlined in the discussion of our first systematic review.2Hvid LG Harwood DL Eskildsen SF Dalgas U A critical systematic review of current evidence on the effects of physical exercise on whole/regional grey matter brain volume in populations at risk of neurodegeneration.Sports Med. 2021; 51: 1651-1671Crossref PubMed Scopus (18) Google Scholar Hence, in the first review, according to the purpose of systematic reviews, we accurately described the existing literature and summarised the evidence leading to a balanced discussion that can help guide the direction and quality of future studies.As for our second systematic review,3Diechmann MD Campbell E Coulter E Paul L Dalgas U Hvid LG Effects of exercise training on neurotrophic factors and subsequent neuroprotection in persons with multiple sclerosis—a systematic review and meta-analysis.Brain Sci. 2021; 111499Crossref PubMed Scopus (6) Google Scholar Sandroff and colleagues1Sandroff BM Motl RW Yong VW Cutter GR Giovannoni G Exercise training in multiple sclerosis.Lancet Neurol. 2022; 21: 313Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar appear to have overlooked its aim to summarise the existing evidence on the effects of exercise training on neurotrophic factors. Although we did note increased chronic levels of BDNF in patients with multiple sclerosis, this increase did not translate into neuroprotection in the few studies examining these levels.Additionally, Sandroff and colleagues1Sandroff BM Motl RW Yong VW Cutter GR Giovannoni G Exercise training in multiple sclerosis.Lancet Neurol. 2022; 21: 313Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar imply that a randomised controlled trial from our group4Langeskov-Christensen M Grøndahl Hvid L Nygaard MKE et al.Efficacy of high-intensity aerobic exercise on brain MRI measures in multiple sclerosis.Neurology. 2021; 96: e203-e213Crossref PubMed Scopus (19) Google Scholar did not involve a priori determined brain regions of interest for studying exercise-induced neuroprotection and relied on structural neuroimaging for generating conclusions on neuroprotection. To clarify, predefined regions of interest were registered at ClinicalTrials.gov (NCT02661555) and we applied extensive state-of-the-art diffusion kurtosis imaging in addition to volumetric neuroimaging.We fully agree with Sandroff and colleagues1Sandroff BM Motl RW Yong VW Cutter GR Giovannoni G Exercise training in multiple sclerosis.Lancet Neurol. 2022; 21: 313Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar that a shift in scientific paradigm is slow and arduous, and that large randomised controlled trials are needed assessing the effect of exercise on neuroprotection in people with multiple sclerosis. We emphasised and thoroughly outlined this scientific paradigm shift in our 2019 review.5Dalgas U Langeskov-Christensen M Stenager E Riemenschneider M Hvid LG Exercise as medicine in multiple sclerosis-time for a paradigm shift: preventive, symptomatic, and disease-modifying aspects and perspectives.Curr Neurol Neurosci Rep. 2019; 19: 88Crossref PubMed Scopus (80) Google ScholarAs should be clear from our publications, we are strong advocates for exercise and its potential for eliciting neuroplasticity and neuroprotection in people with multiple sclerosis, yet we insist on balanced, evidence-based conclusions and recommendations. We encourage and welcome other research groups to help unravel the potential of exercise in multiple sclerosis, as we believe that a joint collaborative research approach is crucial. We read with interest the Correspondence by Brian M Sandroff and colleagues1Sandroff BM Motl RW Yong VW Cutter GR Giovannoni G Exercise training in multiple sclerosis.Lancet Neurol. 2022; 21: 313Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar on exercise training in multiple sclerosis, but believe that the rationale behind this letter could have been based on misconceptions. The authors state that two systematic reviews2Hvid LG Harwood DL Eskildsen SF Dalgas U A critical systematic review of current evidence on the effects of physical exercise on whole/regional grey matter brain volume in populations at risk of neurodegeneration.Sports Med. 2021; 51: 1651-1671Crossref PubMed Scopus (18) Google Scholar, 3Diechmann MD Campbell E Coulter E Paul L Dalgas U Hvid LG Effects of exercise training on neurotrophic factors and subsequent neuroprotection in persons with multiple sclerosis—a systematic review and meta-analysis.Brain Sci. 2021; 111499Crossref PubMed Scopus (6) Google Scholar from our research group conclude that exercise training is not associated with neuroprotection. To clarify, the first systematic review2Hvid LG Harwood DL Eskildsen SF Dalgas U A critical systematic review of current evidence on the effects of physical exercise on whole/regional grey matter brain volume in populations at risk of neurodegeneration.Sports Med. 2021; 51: 1651-1671Crossref PubMed Scopus (18) Google Scholar explicitly states that the evidence on the effects of physical exercise on brain volume in neurodegenerative populations appears sparse and inconclusive, most likely due to the absence of large, long-term (≥1 year), and well-designed studies. Moreover, the arguments put forward by Sandroff and colleagues1Sandroff BM Motl RW Yong VW Cutter GR Giovannoni G Exercise training in multiple sclerosis.Lancet Neurol. 2022; 21: 313Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar are the same as those outlined in the discussion of our first systematic review.2Hvid LG Harwood DL Eskildsen SF Dalgas U A critical systematic review of current evidence on the effects of physical exercise on whole/regional grey matter brain volume in populations at risk of neurodegeneration.Sports Med. 2021; 51: 1651-1671Crossref PubMed Scopus (18) Google Scholar Hence, in the first review, according to the purpose of systematic reviews, we accurately described the existing literature and summarised the evidence leading to a balanced discussion that can help guide the direction and quality of future studies. As for our second systematic review,3Diechmann MD Campbell E Coulter E Paul L Dalgas U Hvid LG Effects of exercise training on neurotrophic factors and subsequent neuroprotection in persons with multiple sclerosis—a systematic review and meta-analysis.Brain Sci. 2021; 111499Crossref PubMed Scopus (6) Google Scholar Sandroff and colleagues1Sandroff BM Motl RW Yong VW Cutter GR Giovannoni G Exercise training in multiple sclerosis.Lancet Neurol. 2022; 21: 313Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar appear to have overlooked its aim to summarise the existing evidence on the effects of exercise training on neurotrophic factors. Although we did note increased chronic levels of BDNF in patients with multiple sclerosis, this increase did not translate into neuroprotection in the few studies examining these levels. Additionally, Sandroff and colleagues1Sandroff BM Motl RW Yong VW Cutter GR Giovannoni G Exercise training in multiple sclerosis.Lancet Neurol. 2022; 21: 313Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar imply that a randomised controlled trial from our group4Langeskov-Christensen M Grøndahl Hvid L Nygaard MKE et al.Efficacy of high-intensity aerobic exercise on brain MRI measures in multiple sclerosis.Neurology. 2021; 96: e203-e213Crossref PubMed Scopus (19) Google Scholar did not involve a priori determined brain regions of interest for studying exercise-induced neuroprotection and relied on structural neuroimaging for generating conclusions on neuroprotection. To clarify, predefined regions of interest were registered at ClinicalTrials.gov (NCT02661555) and we applied extensive state-of-the-art diffusion kurtosis imaging in addition to volumetric neuroimaging. We fully agree with Sandroff and colleagues1Sandroff BM Motl RW Yong VW Cutter GR Giovannoni G Exercise training in multiple sclerosis.Lancet Neurol. 2022; 21: 313Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar that a shift in scientific paradigm is slow and arduous, and that large randomised controlled trials are needed assessing the effect of exercise on neuroprotection in people with multiple sclerosis. We emphasised and thoroughly outlined this scientific paradigm shift in our 2019 review.5Dalgas U Langeskov-Christensen M Stenager E Riemenschneider M Hvid LG Exercise as medicine in multiple sclerosis-time for a paradigm shift: preventive, symptomatic, and disease-modifying aspects and perspectives.Curr Neurol Neurosci Rep. 2019; 19: 88Crossref PubMed Scopus (80) Google Scholar As should be clear from our publications, we are strong advocates for exercise and its potential for eliciting neuroplasticity and neuroprotection in people with multiple sclerosis, yet we insist on balanced, evidence-based conclusions and recommendations. We encourage and welcome other research groups to help unravel the potential of exercise in multiple sclerosis, as we believe that a joint collaborative research approach is crucial. UD has received teaching honorarium from Meyers Squib, Roche, and Biogen Idec. LGH, ML-C, and ES declare no competing interests. Exercise training in multiple sclerosisExercise training has been identified as a neuroprotection-inducing approach in patients with multiple sclerosis.1 However, recently published reviews involving small numbers of randomised controlled trials (RCTs) concluded that exercise training is not associated with neuroprotection.2,3 We argue that the absence of evidence does not constitute evidence of absence. Full-Text PDF
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