CSF Markers of Oxidative Stress Are Associated with Brain Atrophy and Iron Accumulation in a 2-Year Longitudinal Cohort of Early MS

. 2023 Jun 12 ; 24 (12) : . [epub] 20230612

Jazyk angličtina Země Švýcarsko Médium electronic

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/pmid37373196

Grantová podpora
MH CZ-DRO, General University Hospital in Prague-VFN, 00064165 Ministry of Health of the Czech Republic
NV18-08-00062 Ministry of Health of the Czech Republi
Cooperatio, Medical Diagnostics and Basic Medical Sciences, Neuroscience Charles University in Prague
National Institute for Neurological Research, Programme EXCELES, ID Project No. LX22NPO5107 European Union
reg. no. LM2023033 BBMRI.cz
n/A Roche

In this prospective longitudinal study, we quantified regional brain volume and susceptibility changes during the first two years after the diagnosis of multiple sclerosis (MS) and identified their association with cerebrospinal fluid (CSF) markers at baseline. Seventy patients underwent MRI (T1 and susceptibility weighted images processed to quantitative susceptibility maps, QSM) with neurological examination at the diagnosis and after two years. In CSF obtained at baseline, the levels of oxidative stress, products of lipid peroxidation, and neurofilaments light chain (NfL) were determined. Brain volumetry and QSM were compared with a group of 58 healthy controls. In MS patients, regional atrophy was identified in the striatum, thalamus, and substantia nigra. Magnetic susceptibility increased in the striatum, globus pallidus, and dentate and decreased in the thalamus. Compared to controls, MS patients developed greater atrophy of the thalamus, and a greater increase in susceptibility in the caudate, putamen, globus pallidus and a decrease in the thalamus. Of the multiple calculated correlations, only the decrease in brain parenchymal fraction, total white matter, and thalamic volume in MS patients negatively correlated with increased NfL in CSF. Additionally, negative correlation was found between QSM value in the substantia nigra and peroxiredoxin-2, and QSM value in the dentate and lipid peroxidation levels.

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Oh J., Vidal-Jordana A., Montalban X. Multiple Sclerosis: Clinical Aspects. Curr. Opin. Neurol. 2018;31:752–759. doi: 10.1097/WCO.0000000000000622. PubMed DOI

Biernacki T., Kokas Z., Sandi D., Füvesi J., Fricska-Nagy Z., Faragó P., Kincses T.Z., Klivényi P., Bencsik K., Vécsei L. Emerging Biomarkers of Multiple Sclerosis in the Blood and the CSF: A Focus on Neurofilaments and Therapeutic Considerations. Int. J. Mol. Sci. 2022;23:3383. doi: 10.3390/ijms23063383. PubMed DOI PMC

Burgetova A., Dusek P., Uher T., Vaneckova M., Vejrazka M., Burgetova R., Horakova D., Srpova B., Krasensky J., Lambert L. Oxidative Stress Markers in Cerebrospinal Fluid of Newly Diagnosed Multiple Sclerosis Patients and Their Link to Iron Deposition and Atrophy. Diagnostics. 2022;12:1365. doi: 10.3390/diagnostics12061365. PubMed DOI PMC

Uher T., Schaedelin S., Srpova B., Barro C., Bergsland N., Dwyer M., Tyblova M., Vodehnalova K., Benkert P., Oechtering J., et al. Monitoring of Radiologic Disease Activity by Serum Neurofilaments in MS. Neurol. Neuroimmunol. Neuroinflamm. 2020;7:e714. doi: 10.1212/NXI.0000000000000714. PubMed DOI PMC

Khalil M., Pirpamer L., Hofer E., Voortman M.M., Barro C., Leppert D., Benkert P., Ropele S., Enzinger C., Fazekas F., et al. Serum Neurofilament Light Levels in Normal Aging and Their Association with Morphologic Brain Changes. Nat. Commun. 2020;11:812. doi: 10.1038/s41467-020-14612-6. PubMed DOI PMC

Zhang S.-Y., Gui L.-N., Liu Y.-Y., Shi S., Cheng Y. Oxidative Stress Marker Aberrations in Multiple Sclerosis: A Meta-Analysis Study. Front. Neurosci. 2020;14:823. doi: 10.3389/fnins.2020.00823. PubMed DOI PMC

Popescu V., Agosta F., Hulst H.E., Sluimer I.C., Knol D.L., Sormani M.P., Enzinger C., Ropele S., Alonso J., Sastre-Garriga J. Brain Atrophy and Lesion Load Predict Long Term Disability in Multiple Sclerosis. J. Neurol. Neurosurg. Psychiatry. 2013;84:1082–1091. doi: 10.1136/jnnp-2012-304094. PubMed DOI

Burgetova A., Seidl Z., Krasensky J., Horakova D., Vaneckova M. Multiple Sclerosis and the Accumulation of Iron in the Basal Ganglia: Quantitative Assessment of Brain Iron Using MRI T2 Relaxometry. Eur. Neurol. 2010;63:136–143. doi: 10.1159/000279305. PubMed DOI

Pudlac A., Burgetova A., Dusek P., Nytrova P., Vaneckova M., Horakova D., Krasensky J., Lambert L. Deep Gray Matter Iron Content in Neuromyelitis Optica and Multiple Sclerosis. BioMed Res. Int. 2020;2020:6492786. doi: 10.1155/2020/6492786. PubMed DOI PMC

Zhang Y., Gauthier S.A., Gupta A., Comunale J., Chia-Yi Chiang G., Zhou D., Chen W., Giambrone A.E., Zhu W., Wang Y. Longitudinal Change in Magnetic Susceptibility of New Enhanced Multiple Sclerosis (MS) Lesions Measured on Serial Quantitative Susceptibility Mapping (QSM) J. Magn. Reson. Imaging. 2016;44:426–432. doi: 10.1002/jmri.25144. PubMed DOI PMC

Schweser F., Hagemeier J., Dwyer M.G., Bergsland N., Hametner S., Weinstock-Guttman B., Zivadinov R. Decreasing Brain Iron in Multiple Sclerosis: The Difference between Concentration and Content in Iron MRI. Hum. Brain Mapp. 2020;42:1463–1474. doi: 10.1002/hbm.25306. PubMed DOI PMC

Filippi M., Brück W., Chard D., Fazekas F., Geurts J.J., Enzinger C., Hametner S., Kuhlmann T., Preziosa P., Rovira À. Association between Pathological and MRI Findings in Multiple Sclerosis. Lancet Neurol. 2019;18:198–210. doi: 10.1016/S1474-4422(18)30451-4. PubMed DOI

Srpova B., Uher T., Hrnciarova T., Barro C., Andelova M., Michalak Z., Vaneckova M., Krasensky J., Noskova L., Havrdova E.K. Serum Neurofilament Light Chain Reflects Inflammation-Driven Neurodegeneration and Predicts Delayed Brain Volume Loss in Early Stage of Multiple Sclerosis. Mult. Scler. J. 2021;27:52–60. doi: 10.1177/1352458519901272. PubMed DOI

van Lierop Z.Y., Noteboom S., Steenwijk M.D., van Dam M., Toorop A.A., van Kempen Z.L., Moraal B., Barkhof F., Uitdehaag B.M., Schoonheim M.M. Neurofilament-Light and Contactin-1 Association with Long-Term Brain Atrophy in Natalizumab-Treated Relapsing-Remitting Multiple Sclerosis. Mult. Scler. J. 2022;28:2231–2242. doi: 10.1177/13524585221118676. PubMed DOI PMC

Hänninen K., Viitala M., Paavilainen T., Karhu J.O., Rinne J., Koikkalainen J., Lötjönen J., Soilu-Hänninen M. Thalamic Atrophy Predicts 5-Year Disability Progression in Multiple Sclerosis. Front. Neurol. 2020;11:606. doi: 10.3389/fneur.2020.00606. PubMed DOI PMC

Bergsland N., Benedict R.H.B., Dwyer M.G., Fuchs T.A., Jakimovski D., Schweser F., Tavazzi E., Weinstock-Guttman B., Zivadinov R. Thalamic Nuclei Volumes and Their Relationships to Neuroperformance in Multiple Sclerosis: A Cross-Sectional Structural MRI Study. J. Magn. Reson. Imaging JMRI. 2021;53:731–739. doi: 10.1002/jmri.27389. PubMed DOI

Rocca M.A., Valsasina P., Meani A., Gobbi C., Zecca C., Rovira A., Sastre-Garriga J., Kearney H., Ciccarelli O., Matthews L., et al. Association of Gray Matter Atrophy Patterns With Clinical Phenotype and Progression in Multiple Sclerosis. Neurology. 2021;96:e1561–e1573. doi: 10.1212/WNL.0000000000011494. PubMed DOI

Steffen F., Uphaus T., Ripfel N., Fleischer V., Schraad M., Gonzalez-Escamilla G., Engel S., Groppa S., Zipp F., Bittner S. Serum Neurofilament Identifies Patients with Multiple Sclerosis with Severe Focal Axonal Damage in a 6-Year Longitudinal Cohort. Neurol. Neuroimmunol. Neuroinflamm. 2022;10:e200055. doi: 10.1212/NXI.0000000000200055. PubMed DOI PMC

Martin S.-J., McGlasson S., Hunt D., Overell J. Cerebrospinal Fluid Neurofilament Light Chain in Multiple Sclerosis and Its Subtypes: A Meta-Analysis of Case–control Studies. J. Neurol. Neurosurg. Psychiatry. 2019;90:1059–1067. doi: 10.1136/jnnp-2018-319190. PubMed DOI PMC

Ziemssen T., Arnold D.L., Alvarez E., Cross A.H., Willi R., Li B., Kukkaro P., Kropshofer H., Ramanathan K., Merschhemke M., et al. Prognostic Value of Serum Neurofilament Light Chain for Disease Activity and Worsening in Patients with Relapsing Multiple Sclerosis: Results from the Phase 3 ASCLEPIOS I and II Trials. Front. Immunol. 2022;13:852563. doi: 10.3389/fimmu.2022.852563. PubMed DOI PMC

Zivadinov R., Bergsland N., Jakimovski D., Weinstock-Guttman B., Benedict R.H.B., Riolo J., Silva D., Dwyer M.G. Thalamic Atrophy Measured by Artificial Intelligence in a Multicentre Clinical Routine Real-World Study Is Associated with Disability Progression. J. Neurol. Neurosurg. Psychiatry. 2022;93:1128–1136. doi: 10.1136/jnnp-2022-329333. PubMed DOI

Jakimovski D., Bergsland N., Dwyer M.G., Ramasamy D.P., Ramanathan M., Weinstock-Guttman B., Zivadinov R. Serum Neurofilament Light Chain Levels Are Associated with Lower Thalamic Perfusion in Multiple Sclerosis. Diagnostics. 2020;10:685. doi: 10.3390/diagnostics10090685. PubMed DOI PMC

Bagnato F., Hametner S., Yao B., van Gelderen P., Merkle H., Cantor F.K., Lassmann H., Duyn J.H. Tracking Iron in Multiple Sclerosis: A Combined Imaging and Histopathological Study at 7 Tesla. Brain J. Neurol. 2011;134:3602–3615. doi: 10.1093/brain/awr278. PubMed DOI PMC

Hagemeier J., Zivadinov R., Dwyer M.G., Polak P., Bergsland N., Weinstock-Guttman B., Zalis J., Deistung A., Reichenbach J.R., Schweser F. Changes of Deep Gray Matter Magnetic Susceptibility over 2 Years in Multiple Sclerosis and Healthy Control Brain. NeuroImage Clin. 2017;18:1007–1016. doi: 10.1016/j.nicl.2017.04.008. PubMed DOI PMC

Haider L., Simeonidou C., Steinberger G., Hametner S., Grigoriadis N., Deretzi G., Kovacs G.G., Kutzelnigg A., Lassmann H., Frischer J.M. Multiple Sclerosis Deep Grey Matter: The Relation between Demyelination, Neurodegeneration, Inflammation and Iron. J. Neurol. Neurosurg. Psychiatry. 2014;85:1386–1395. doi: 10.1136/jnnp-2014-307712. PubMed DOI PMC

Langkammer C., Schweser F., Krebs N., Deistung A., Goessler W., Scheurer E., Sommer K., Reishofer G., Yen K., Fazekas F., et al. Quantitative Susceptibility Mapping (QSM) as a Means to Measure Brain Iron? A Post Mortem Validation Study. NeuroImage. 2012;62:1593–1599. doi: 10.1016/j.neuroimage.2012.05.049. PubMed DOI PMC

Burgetova A., Dusek P., Vaneckova M., Horakova D., Langkammer C., Krasensky J., Sobisek L., Matras P., Masek M., Seidl Z. Thalamic Iron Differentiates Primary-Progressive and Relapsing-Remitting Multiple Sclerosis. AJNR Am. J. Neuroradiol. 2017;38:1079–1086. doi: 10.3174/ajnr.A5166. PubMed DOI PMC

Khalil M., Langkammer C., Pichler A., Pinter D., Gattringer T., Bachmaier G., Ropele S., Fuchs S., Enzinger C., Fazekas F. Dynamics of Brain Iron Levels in Multiple Sclerosis: A Longitudinal 3T MRI Study. Neurology. 2015;84:2396–2402. doi: 10.1212/WNL.0000000000001679. PubMed DOI

Voigt D., Scheidt U., Derfuss T., Brück W., Junker A. Expression of the Antioxidative Enzyme Peroxiredoxin 2 in Multiple Sclerosis Lesions in Relation to Inflammation. Int. J. Mol. Sci. 2017;18:760. doi: 10.3390/ijms18040760. PubMed DOI PMC

Haider L., Fischer M.T., Frischer J.M., Bauer J., Höftberger R., Botond G., Esterbauer H., Binder C.J., Witztum J.L., Lassmann H. Oxidative Damage in Multiple Sclerosis Lesions. Brain J. Neurol. 2011;134:1914–1924. doi: 10.1093/brain/awr128. PubMed DOI PMC

Ghonimi N.A.M., Elsharkawi K.A., Khyal D.S.M., Abdelghani A.A. Serum Malondialdehyde as a Lipid Peroxidation Marker in Multiple Sclerosis Patients and Its Relation to Disease Characteristics. Mult. Scler. Relat. Disord. 2021;51:102941. doi: 10.1016/j.msard.2021.102941. PubMed DOI

Uzawa A., Mori M., Masuda H., Ohtani R., Uchida T., Aoki R., Kuwabara S. Peroxiredoxins Are Involved in the Pathogenesis of Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder. Clin. Exp. Immunol. 2020;202:239–248. doi: 10.1111/cei.13487. PubMed DOI PMC

Keles M.S., Taysi S., Sen N., Aksoy H., Akçay F. Effect of Corticosteroid Therapy on Serum and CSF Malondialdehyde and Antioxidant Proteins in Multiple Sclerosis. Can. J. Neurol. Sci. 2001;28:141–143. doi: 10.1017/S0317167100052823. PubMed DOI

Reeves J.A., Bergsland N., Dwyer M.G., Wilding G.E., Jakimovski D., Salman F., Sule B., Meineke N., Weinstock-Guttman B., Zivadinov R., et al. Susceptibility Networks Reveal Independent Patterns of Brain Iron Abnormalities in Multiple Sclerosis. NeuroImage. 2022;261:119503. doi: 10.1016/j.neuroimage.2022.119503. PubMed DOI PMC

Blazejewska A.I., Al-Radaideh A.M., Wharton S., Lim S.Y., Bowtell R.W., Constantinescu C.S., Gowland P.A. Increase in the Iron Content of the Substantia Nigra and Red Nucleus in Multiple Sclerosis and Clinically Isolated Syndrome: A 7 Tesla MRI Study. J. Magn. Reson. Imaging. 2015;41:1065–1070. doi: 10.1002/jmri.24644. PubMed DOI

Moezzi D., Dong Y., Jain R.W., Lozinski B.M., Ghorbani S., D’Mello C., Wee Yong V. Expression of Antioxidant Enzymes in Lesions of Multiple Sclerosis and Its Models. Sci. Rep. 2022;12:12761. doi: 10.1038/s41598-022-16840-w. PubMed DOI PMC

Singhal T., Cicero S., Pan H., Carter K., Dubey S., Chu R., Glanz B., Hurwitz S., Tauhid S., Park M.-A., et al. Regional Microglial Activation in the Substantia Nigra Is Linked with Fatigue in MS. Neurol. Neuroimmunol. Neuroinflamm. 2020;7:e854. doi: 10.1212/NXI.0000000000000854. PubMed DOI PMC

Franceschi L.D., Bertoldi M., Falco L.D., Franco S.S., Ronzoni L., Turrini F., Colancecco A., Camaschella C., Cappellini M.D., Iolascon A. Oxidative stress modulates heme synthesis and induces peroxiredoxin-2 as a novel cytoprotective response in β-thalassemic erythropoiesis. Haematologica. 2011;96:1595–1604. doi: 10.3324/haematol.2011.043612. PubMed DOI PMC

Krata N., Foroncewicz B., Zagożdżon R., Moszczuk B., Zielenkiewicz M., Pączek L., Mucha K. Peroxiredoxins as Markers of Oxidative Stress in IgA Nephropathy, Membranous Nephropathy and Lupus Nephritis. Arch. Immunol. Exp. 2021;70:3. doi: 10.1007/s00005-021-00638-1. PubMed DOI PMC

Albert M., Barrantes-Freer A., Lohrberg M., Antel J.P., Prineas J.W., Palkovits M., Wolff J.R., Brück W., Stadelmann C. Synaptic Pathology in the Cerebellar Dentate Nucleus in Chronic Multiple Sclerosis. Brain Pathol. 2017;27:737–747. doi: 10.1111/bpa.12450. PubMed DOI PMC

Ayala A., Muñoz M.F., Argüelles S. Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde and 4-Hydroxy-2-Nonenal. Oxid. Med. Cell. Longev. 2014;2014:360438. doi: 10.1155/2014/360438. PubMed DOI PMC

Maciejczyk M., Żebrowska E., Zalewska A., Chabowski A. Redox Balance, Antioxidant Defense, and Oxidative Damage in the Hypothalamus and Cerebral Cortex of Rats with High Fat Diet-Induced Insulin Resistance. Oxid. Med. Cell. Longev. 2018;2018:6940515. doi: 10.1155/2018/6940515. PubMed DOI PMC

Ferretti G., Bacchetti T. Peroxidation of Lipoproteins in Multiple Sclerosis. J. Neurol. Sci. 2011;311:92–97. doi: 10.1016/j.jns.2011.09.004. PubMed DOI

Thompson A.J., Banwell B.L., Barkhof F., Carroll W.M., Coetzee T., Comi G., Correale J., Fazekas F., Filippi M., Freedman M.S., et al. Diagnosis of Multiple Sclerosis: 2017 Revisions of the McDonald Criteria. Lancet Neurol. 2018;17:162–173. doi: 10.1016/S1474-4422(17)30470-2. PubMed DOI

Burgetova R., Dusek P., Burgetova A., Pudlac A., Vaneckova M., Horakova D., Krasensky J., Varga Z., Lambert L. Age-Related Magnetic Susceptibility Changes in Deep Grey Matter and Cerebral Cortex of Normal Young and Middle-Aged Adults Depicted by Whole Brain Analysis. Quant. Imaging Med. Surg. 2021;11:3903919–3906919. doi: 10.21037/qims-21-87. PubMed DOI PMC

Acosta-Cabronero J., Milovic C., Mattern H., Tejos C., Speck O., Callaghan M.F. A Robust Multi-Scale Approach to Quantitative Susceptibility Mapping. NeuroImage. 2018;183:7–24. doi: 10.1016/j.neuroimage.2018.07.065. PubMed DOI PMC

Schmidt P., Gaser C., Arsic M., Buck D., Förschler A., Berthele A., Hoshi M., Ilg R., Schmid V.J., Zimmer C., et al. An Automated Tool for Detection of FLAIR-Hyperintense White-Matter Lesions in Multiple Sclerosis. NeuroImage. 2012;59:3774–3783. doi: 10.1016/j.neuroimage.2011.11.032. PubMed DOI

Mori S., Wu D., Ceritoglu C., Li Y., Kolasny A., Vaillant M.A., Faria A.V., Oishi K., Miller M.I. MRICloud: Delivering High-Throughput MRI Neuroinformatics as Cloud-Based Software as a Service. Comput. Sci. Eng. 2016;18:21–35. doi: 10.1109/MCSE.2016.93. DOI

Ward P.G., Harding I.H., Close T.G., Corben L.A., Delatycki M.B., Storey E., Georgiou-Karistianis N., Egan G.F. Longitudinal Evaluation of Iron Concentration and Atrophy in the Dentate Nuclei in Friedreich Ataxia. Mov. Disord. 2019;34:335–343. doi: 10.1002/mds.27606. PubMed DOI

Hernández-Torres E., Wiggermann V., Machan L., Sadovnick A.D., Li D.K., Traboulsee A., Hametner S., Rauscher A. Increased Mean R2* in the Deep Gray Matter of Multiple Sclerosis Patients: Have We Been Measuring Atrophy? J. Magn. Reson. Imaging. 2019;50:201–208. doi: 10.1002/jmri.26561. PubMed DOI

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