Stratifying the presymptomatic phase of genetic frontotemporal dementia by Serum NfL and pNfH: a longitudinal multicentre study

Detalhes bibliográficos
Autor(a) principal: Wilke, Carlo
Data de Publicação: 2021
Outros Autores: Reich, Selina, Swieten, John C., Borroni, Barbara, Sanchez‐Valle, Raquel, Moreno, Fermin, Laforce, Robert, Graff, Caroline, Galimberti, Daniela, Rowe, James B., Masellis, Mario, Tartaglia, Maria C., Finger, Elizabeth, Vandenberghe, Rik, De Mendonça, Alexandre, Tagliavini, Fabrizio, Santana, Isabel, Ducharme, Simon, Butler, Chris R., Gerhard, Alexander, Levin, Johannes, Danek, Adrian, Otto, Markus, Frisoni, Giovanni, Ghidoni, Roberta, Sorbi, Sandro, Bocchetta, Martina, Todd, Emily, Kuhle, Jens, Barro, Christian, Afonso, Sónia, Almeida, Maria Rosario, Anderl‐Straub, Sarah, Andersson, Christin, Antonell, Anna, Archetti, Silvana, Arighi, Andrea, Balasa, Mircea, Barandiaran, Myriam, Bargalló, Nuria, Bartha, Robart, Bender, Benjamin, Benussi, Alberto, Benussi, Luisa, Bessi, Valentina, Binetti, Giuliano, Black, Sandra, Borrego‐Ecija, Sergi, Bras, Jose, Bruffaerts, Rose, Cañada, Marta, Cantoni, Valentina, Caroppo, Paola, Cash, David, Castelo-Branco, Miguel, Convery, Rhian, Cope, Thomas, Di Fede, Giuseppe, Díez, Alina, Duro, Diana, Fenoglio, Chiara, Ferrari, Camilla, Ferreira, Catarina B., Fox, Nick, Freedman, Morris, Fumagalli, Giorgio, Gabilondo, Alazne, Gasparotti, Roberto, Gauthier, Serge, Gazzina, Stefano, Giaccone, Giorgio, Gorostidi, Ana, Greaves, Caroline, Guerreiro, Rita, Heller, Carolin, Hoegen, Tobias, Indakoetxea, Begoña, Jelic, Vesna, Jiskoot, Lize, Karnath, Hans‐Otto, Keren, Ron, Langheinrich, Tobias, Leitão, Maria João, Lladó, Albert, Lombardi, Gemma, Loosli, Sandra, Maruta, Carolina, Mead, Simon, Meeter, Lieke, Miltenberger-Miltenyi, Gabriel, Minkelen, Rick, Mitchell, Sara, Moore, Katrina, Nacmias, Benedetta, Nicholas, Jennifer, Öijerstedt, Linn, Olives, Jaume, Ourselin, Sebastien, Padovani, Alessandro, Panman, Jessica, Papma, Janne M., Peakman, Georgia, Pievani, Michela, Pijnenburg, Yolande, Polito, Cristina, Premi, Enrico, Prioni, Sara, Prix, Catharina, Rademakers, Rosa, Redaelli, Veronica, Rittman, Tim, Rogaeva, Ekaterina, Rosa‐Neto, Pedro, Rossi, Giacomina, Rosser, Martin, Santiago, Beatriz, Scarpini, Elio, Schönecker, Sonja, Seelaar, Harro, Semler, Elisa, Shafei, Rachelle, Shoesmith, Christen, Tábuas‐Pereira, Miguel, Tainta, Mikel, Taipa, Ricardo, Tang‐Wai, David, Thomas, David L., Thompson, Paul, Thonberg, Hakan, Timberlake, Carolyn, Tiraboschi, Pietro, Van Damme, Philip, Vandenbulcke, Mathieu, Veldsman, Michele, Verdelho, Ana, Villanua, Jorge, Warren, Jason, Woollacott, Ione, Wlasich, Elisabeth, Zetterberg, Henrik, Zulaica, Miren, Rohrer, Jonathan D., Synofzik, Matthis
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/50716
Resumo: © 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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spelling Stratifying the presymptomatic phase of genetic frontotemporal dementia by Serum NfL and pNfH: a longitudinal multicentre study© 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Objective: Although the presymptomatic stages of frontotemporal dementia (FTD) provide a unique chance to delay or even prevent neurodegeneration by early intervention, they remain poorly defined. Leveraging a large multicenter cohort of genetic FTD mutation carriers, we provide a biomarker-based stratification and biomarker cascade of the likely most treatment-relevant stage within the presymptomatic phase: the conversion stage. Methods: We longitudinally assessed serum levels of neurofilament light (NfL) and phosphorylated neurofilament heavy (pNfH) in the Genetic FTD Initiative (GENFI) cohort (n = 444), using single-molecule array technique. Subjects comprised 91 symptomatic and 179 presymptomatic subjects with mutations in the FTD genes C9orf72, GRN, or MAPT, and 174 mutation-negative within-family controls. Results: In a biomarker cascade, NfL increase preceded the hypothetical clinical onset by 15 years and concurred with brain atrophy onset, whereas pNfH increase started close to clinical onset. The conversion stage was marked by increased NfL, but still normal pNfH levels, while both were increased at the symptomatic stage. Intra-individual change rates were increased for NfL at the conversion stage and for pNfH at the symptomatic stage, highlighting their respective potential as stage-dependent dynamic biomarkers within the biomarker cascade. Increased NfL levels and NfL change rates allowed identification of presymptomatic subjects converting to symptomatic disease and capture of proximity-to-onset. We estimate stage-dependent sample sizes for trials aiming to decrease neurofilament levels or change rates. Interpretation: Blood NfL and pNfH provide dynamic stage-dependent stratification and, potentially, treatment response biomarkers in presymptomatic FTD, allowing demarcation of the conversion stage. The proposed biomarker cascade might pave the way towards a biomarker-based precision medicine approach to genetic FTD..W. and M.S. are members of the European Reference Network for Rare Neurological Diseases Project ID No. 739510. This work was supported by the Horizon 2020 research and innovation program (grant 779257 Solve-RD to M.S.), the National Ataxia Foundation (grant to C.W. and M.S.), the Wilhelm Vaillant Stiftung (grant to C.W.), the EU Joint Programme – Neurodegenerative Disease Research (JPND) “GENFI-prox” through participating national funding agencies (by DLR/BMBF to M.S., J.D.R., B.B., C.G., and M.O.), and the European Union's Horizon 2020 research and innovation programme under grant agreement No. 643417. J.C.S. and H.S. received funding by two Memorabel grants from Deltaplan Dementie (The Netherlands Organisation for Health Research and Development and Alzheimer Nederland; grant numbers 733050813 and 733050103) in the Netherlands and the Bluefield Project to Cure Frontotemporal Dementia. J.B.R. was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014) and the Medical Research Council (SUAG/051 G101400). C.B. is supported by a postdoctoral fellowship from the Swiss National Science Foundation (P400PM_191077). J.D.R. is supported by the Miriam Marks Brain Research UK Senior Fellowship and has received funding from an MRC Clinician Scientist Fellowship (MR/M008525/1) and the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). This work was also supported by the MRC UK GENFI grant (MR/M023664/1), the Bluefield Project and the JPND GENFI-PROX grant (2019-02248).WileyRepositório da Universidade de LisboaWilke, CarloReich, SelinaSwieten, John C.Borroni, BarbaraSanchez‐Valle, RaquelMoreno, FerminLaforce, RobertGraff, CarolineGalimberti, DanielaRowe, James B.Masellis, MarioTartaglia, Maria C.Finger, ElizabethVandenberghe, RikDe Mendonça, AlexandreTagliavini, FabrizioSantana, IsabelDucharme, SimonButler, Chris R.Gerhard, AlexanderLevin, JohannesDanek, AdrianOtto, MarkusFrisoni, GiovanniGhidoni, RobertaSorbi, SandroBocchetta, MartinaTodd, EmilyKuhle, JensBarro, ChristianAfonso, SóniaAlmeida, Maria RosarioAnderl‐Straub, SarahAndersson, ChristinAntonell, AnnaArchetti, SilvanaArighi, AndreaBalasa, MirceaBarandiaran, MyriamBargalló, NuriaBartha, RobartBender, BenjaminBenussi, AlbertoBenussi, LuisaBessi, ValentinaBinetti, GiulianoBlack, SandraBorrego‐Ecija, SergiBras, JoseBruffaerts, RoseCañada, MartaCantoni, ValentinaCaroppo, PaolaCash, DavidCastelo-Branco, MiguelConvery, RhianCope, ThomasDi Fede, GiuseppeDíez, AlinaDuro, DianaFenoglio, ChiaraFerrari, CamillaFerreira, Catarina B.Fox, NickFreedman, MorrisFumagalli, GiorgioGabilondo, AlazneGasparotti, RobertoGauthier, SergeGazzina, StefanoGiaccone, GiorgioGorostidi, AnaGreaves, CarolineGuerreiro, RitaHeller, CarolinHoegen, TobiasIndakoetxea, BegoñaJelic, VesnaJiskoot, LizeKarnath, Hans‐OttoKeren, RonLangheinrich, TobiasLeitão, Maria JoãoLladó, AlbertLombardi, GemmaLoosli, SandraMaruta, CarolinaMead, SimonMeeter, LiekeMiltenberger-Miltenyi, GabrielMinkelen, RickMitchell, SaraMoore, KatrinaNacmias, BenedettaNicholas, JenniferÖijerstedt, LinnOlives, JaumeOurselin, SebastienPadovani, AlessandroPanman, JessicaPapma, Janne M.Peakman, GeorgiaPievani, MichelaPijnenburg, YolandePolito, CristinaPremi, EnricoPrioni, SaraPrix, CatharinaRademakers, RosaRedaelli, VeronicaRittman, TimRogaeva, EkaterinaRosa‐Neto, PedroRossi, GiacominaRosser, MartinSantiago, BeatrizScarpini, ElioSchönecker, SonjaSeelaar, HarroSemler, ElisaShafei, RachelleShoesmith, ChristenTábuas‐Pereira, MiguelTainta, MikelTaipa, RicardoTang‐Wai, DavidThomas, David L.Thompson, PaulThonberg, HakanTimberlake, CarolynTiraboschi, PietroVan Damme, PhilipVandenbulcke, MathieuVeldsman, MicheleVerdelho, AnaVillanua, JorgeWarren, JasonWoollacott, IoneWlasich, ElisabethZetterberg, HenrikZulaica, MirenRohrer, Jonathan D.Synofzik, Matthis2022-01-05T16:49:20Z20212021-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/50716engAnn Neurol. 2022 Jan;91(1):33-470364-513410.1002/ana.262651531-8249info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:55:02Zoai:repositorio.ul.pt:10451/50716Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:02:07.203345Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Stratifying the presymptomatic phase of genetic frontotemporal dementia by Serum NfL and pNfH: a longitudinal multicentre study
title Stratifying the presymptomatic phase of genetic frontotemporal dementia by Serum NfL and pNfH: a longitudinal multicentre study
spellingShingle Stratifying the presymptomatic phase of genetic frontotemporal dementia by Serum NfL and pNfH: a longitudinal multicentre study
Wilke, Carlo
title_short Stratifying the presymptomatic phase of genetic frontotemporal dementia by Serum NfL and pNfH: a longitudinal multicentre study
title_full Stratifying the presymptomatic phase of genetic frontotemporal dementia by Serum NfL and pNfH: a longitudinal multicentre study
title_fullStr Stratifying the presymptomatic phase of genetic frontotemporal dementia by Serum NfL and pNfH: a longitudinal multicentre study
title_full_unstemmed Stratifying the presymptomatic phase of genetic frontotemporal dementia by Serum NfL and pNfH: a longitudinal multicentre study
title_sort Stratifying the presymptomatic phase of genetic frontotemporal dementia by Serum NfL and pNfH: a longitudinal multicentre study
author Wilke, Carlo
author_facet Wilke, Carlo
Reich, Selina
Swieten, John C.
Borroni, Barbara
Sanchez‐Valle, Raquel
Moreno, Fermin
Laforce, Robert
Graff, Caroline
Galimberti, Daniela
Rowe, James B.
Masellis, Mario
Tartaglia, Maria C.
Finger, Elizabeth
Vandenberghe, Rik
De Mendonça, Alexandre
Tagliavini, Fabrizio
Santana, Isabel
Ducharme, Simon
Butler, Chris R.
Gerhard, Alexander
Levin, Johannes
Danek, Adrian
Otto, Markus
Frisoni, Giovanni
Ghidoni, Roberta
Sorbi, Sandro
Bocchetta, Martina
Todd, Emily
Kuhle, Jens
Barro, Christian
Afonso, Sónia
Almeida, Maria Rosario
Anderl‐Straub, Sarah
Andersson, Christin
Antonell, Anna
Archetti, Silvana
Arighi, Andrea
Balasa, Mircea
Barandiaran, Myriam
Bargalló, Nuria
Bartha, Robart
Bender, Benjamin
Benussi, Alberto
Benussi, Luisa
Bessi, Valentina
Binetti, Giuliano
Black, Sandra
Borrego‐Ecija, Sergi
Bras, Jose
Bruffaerts, Rose
Cañada, Marta
Cantoni, Valentina
Caroppo, Paola
Cash, David
Castelo-Branco, Miguel
Convery, Rhian
Cope, Thomas
Di Fede, Giuseppe
Díez, Alina
Duro, Diana
Fenoglio, Chiara
Ferrari, Camilla
Ferreira, Catarina B.
Fox, Nick
Freedman, Morris
Fumagalli, Giorgio
Gabilondo, Alazne
Gasparotti, Roberto
Gauthier, Serge
Gazzina, Stefano
Giaccone, Giorgio
Gorostidi, Ana
Greaves, Caroline
Guerreiro, Rita
Heller, Carolin
Hoegen, Tobias
Indakoetxea, Begoña
Jelic, Vesna
Jiskoot, Lize
Karnath, Hans‐Otto
Keren, Ron
Langheinrich, Tobias
Leitão, Maria João
Lladó, Albert
Lombardi, Gemma
Loosli, Sandra
Maruta, Carolina
Mead, Simon
Meeter, Lieke
Miltenberger-Miltenyi, Gabriel
Minkelen, Rick
Mitchell, Sara
Moore, Katrina
Nacmias, Benedetta
Nicholas, Jennifer
Öijerstedt, Linn
Olives, Jaume
Ourselin, Sebastien
Padovani, Alessandro
Panman, Jessica
Papma, Janne M.
Peakman, Georgia
Pievani, Michela
Pijnenburg, Yolande
Polito, Cristina
Premi, Enrico
Prioni, Sara
Prix, Catharina
Rademakers, Rosa
Redaelli, Veronica
Rittman, Tim
Rogaeva, Ekaterina
Rosa‐Neto, Pedro
Rossi, Giacomina
Rosser, Martin
Santiago, Beatriz
Scarpini, Elio
Schönecker, Sonja
Seelaar, Harro
Semler, Elisa
Shafei, Rachelle
Shoesmith, Christen
Tábuas‐Pereira, Miguel
Tainta, Mikel
Taipa, Ricardo
Tang‐Wai, David
Thomas, David L.
Thompson, Paul
Thonberg, Hakan
Timberlake, Carolyn
Tiraboschi, Pietro
Van Damme, Philip
Vandenbulcke, Mathieu
Veldsman, Michele
Verdelho, Ana
Villanua, Jorge
Warren, Jason
Woollacott, Ione
Wlasich, Elisabeth
Zetterberg, Henrik
Zulaica, Miren
Rohrer, Jonathan D.
Synofzik, Matthis
author_role author
author2 Reich, Selina
Swieten, John C.
Borroni, Barbara
Sanchez‐Valle, Raquel
Moreno, Fermin
Laforce, Robert
Graff, Caroline
Galimberti, Daniela
Rowe, James B.
Masellis, Mario
Tartaglia, Maria C.
Finger, Elizabeth
Vandenberghe, Rik
De Mendonça, Alexandre
Tagliavini, Fabrizio
Santana, Isabel
Ducharme, Simon
Butler, Chris R.
Gerhard, Alexander
Levin, Johannes
Danek, Adrian
Otto, Markus
Frisoni, Giovanni
Ghidoni, Roberta
Sorbi, Sandro
Bocchetta, Martina
Todd, Emily
Kuhle, Jens
Barro, Christian
Afonso, Sónia
Almeida, Maria Rosario
Anderl‐Straub, Sarah
Andersson, Christin
Antonell, Anna
Archetti, Silvana
Arighi, Andrea
Balasa, Mircea
Barandiaran, Myriam
Bargalló, Nuria
Bartha, Robart
Bender, Benjamin
Benussi, Alberto
Benussi, Luisa
Bessi, Valentina
Binetti, Giuliano
Black, Sandra
Borrego‐Ecija, Sergi
Bras, Jose
Bruffaerts, Rose
Cañada, Marta
Cantoni, Valentina
Caroppo, Paola
Cash, David
Castelo-Branco, Miguel
Convery, Rhian
Cope, Thomas
Di Fede, Giuseppe
Díez, Alina
Duro, Diana
Fenoglio, Chiara
Ferrari, Camilla
Ferreira, Catarina B.
Fox, Nick
Freedman, Morris
Fumagalli, Giorgio
Gabilondo, Alazne
Gasparotti, Roberto
Gauthier, Serge
Gazzina, Stefano
Giaccone, Giorgio
Gorostidi, Ana
Greaves, Caroline
Guerreiro, Rita
Heller, Carolin
Hoegen, Tobias
Indakoetxea, Begoña
Jelic, Vesna
Jiskoot, Lize
Karnath, Hans‐Otto
Keren, Ron
Langheinrich, Tobias
Leitão, Maria João
Lladó, Albert
Lombardi, Gemma
Loosli, Sandra
Maruta, Carolina
Mead, Simon
Meeter, Lieke
Miltenberger-Miltenyi, Gabriel
Minkelen, Rick
Mitchell, Sara
Moore, Katrina
Nacmias, Benedetta
Nicholas, Jennifer
Öijerstedt, Linn
Olives, Jaume
Ourselin, Sebastien
Padovani, Alessandro
Panman, Jessica
Papma, Janne M.
Peakman, Georgia
Pievani, Michela
Pijnenburg, Yolande
Polito, Cristina
Premi, Enrico
Prioni, Sara
Prix, Catharina
Rademakers, Rosa
Redaelli, Veronica
Rittman, Tim
Rogaeva, Ekaterina
Rosa‐Neto, Pedro
Rossi, Giacomina
Rosser, Martin
Santiago, Beatriz
Scarpini, Elio
Schönecker, Sonja
Seelaar, Harro
Semler, Elisa
Shafei, Rachelle
Shoesmith, Christen
Tábuas‐Pereira, Miguel
Tainta, Mikel
Taipa, Ricardo
Tang‐Wai, David
Thomas, David L.
Thompson, Paul
Thonberg, Hakan
Timberlake, Carolyn
Tiraboschi, Pietro
Van Damme, Philip
Vandenbulcke, Mathieu
Veldsman, Michele
Verdelho, Ana
Villanua, Jorge
Warren, Jason
Woollacott, Ione
Wlasich, Elisabeth
Zetterberg, Henrik
Zulaica, Miren
Rohrer, Jonathan D.
Synofzik, Matthis
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dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Wilke, Carlo
Reich, Selina
Swieten, John C.
Borroni, Barbara
Sanchez‐Valle, Raquel
Moreno, Fermin
Laforce, Robert
Graff, Caroline
Galimberti, Daniela
Rowe, James B.
Masellis, Mario
Tartaglia, Maria C.
Finger, Elizabeth
Vandenberghe, Rik
De Mendonça, Alexandre
Tagliavini, Fabrizio
Santana, Isabel
Ducharme, Simon
Butler, Chris R.
Gerhard, Alexander
Levin, Johannes
Danek, Adrian
Otto, Markus
Frisoni, Giovanni
Ghidoni, Roberta
Sorbi, Sandro
Bocchetta, Martina
Todd, Emily
Kuhle, Jens
Barro, Christian
Afonso, Sónia
Almeida, Maria Rosario
Anderl‐Straub, Sarah
Andersson, Christin
Antonell, Anna
Archetti, Silvana
Arighi, Andrea
Balasa, Mircea
Barandiaran, Myriam
Bargalló, Nuria
Bartha, Robart
Bender, Benjamin
Benussi, Alberto
Benussi, Luisa
Bessi, Valentina
Binetti, Giuliano
Black, Sandra
Borrego‐Ecija, Sergi
Bras, Jose
Bruffaerts, Rose
Cañada, Marta
Cantoni, Valentina
Caroppo, Paola
Cash, David
Castelo-Branco, Miguel
Convery, Rhian
Cope, Thomas
Di Fede, Giuseppe
Díez, Alina
Duro, Diana
Fenoglio, Chiara
Ferrari, Camilla
Ferreira, Catarina B.
Fox, Nick
Freedman, Morris
Fumagalli, Giorgio
Gabilondo, Alazne
Gasparotti, Roberto
Gauthier, Serge
Gazzina, Stefano
Giaccone, Giorgio
Gorostidi, Ana
Greaves, Caroline
Guerreiro, Rita
Heller, Carolin
Hoegen, Tobias
Indakoetxea, Begoña
Jelic, Vesna
Jiskoot, Lize
Karnath, Hans‐Otto
Keren, Ron
Langheinrich, Tobias
Leitão, Maria João
Lladó, Albert
Lombardi, Gemma
Loosli, Sandra
Maruta, Carolina
Mead, Simon
Meeter, Lieke
Miltenberger-Miltenyi, Gabriel
Minkelen, Rick
Mitchell, Sara
Moore, Katrina
Nacmias, Benedetta
Nicholas, Jennifer
Öijerstedt, Linn
Olives, Jaume
Ourselin, Sebastien
Padovani, Alessandro
Panman, Jessica
Papma, Janne M.
Peakman, Georgia
Pievani, Michela
Pijnenburg, Yolande
Polito, Cristina
Premi, Enrico
Prioni, Sara
Prix, Catharina
Rademakers, Rosa
Redaelli, Veronica
Rittman, Tim
Rogaeva, Ekaterina
Rosa‐Neto, Pedro
Rossi, Giacomina
Rosser, Martin
Santiago, Beatriz
Scarpini, Elio
Schönecker, Sonja
Seelaar, Harro
Semler, Elisa
Shafei, Rachelle
Shoesmith, Christen
Tábuas‐Pereira, Miguel
Tainta, Mikel
Taipa, Ricardo
Tang‐Wai, David
Thomas, David L.
Thompson, Paul
Thonberg, Hakan
Timberlake, Carolyn
Tiraboschi, Pietro
Van Damme, Philip
Vandenbulcke, Mathieu
Veldsman, Michele
Verdelho, Ana
Villanua, Jorge
Warren, Jason
Woollacott, Ione
Wlasich, Elisabeth
Zetterberg, Henrik
Zulaica, Miren
Rohrer, Jonathan D.
Synofzik, Matthis
description © 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021-01-01T00:00:00Z
2022-01-05T16:49:20Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/50716
url http://hdl.handle.net/10451/50716
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Ann Neurol. 2022 Jan;91(1):33-47
0364-5134
10.1002/ana.26265
1531-8249
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eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Wiley
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