Preserved structural connectivity mediates the clinical effect of thrombolysis in patients with anterior-circulation stroke
E. Schlemm
(1)
,
T. Ingwersen
(1)
,
A. Königsberg
(1)
,
F. Boutitie
(2, 3, 4)
,
M. Ebinger
(5, 6)
,
M. Endres
(5, 7, 8, 9)
,
J. B. Fiebach
(6)
,
J. Fiehler
(1)
,
I. Galinovic
(5)
,
R. Lemmens
(10, 11, 12)
,
K. W. Muir
(13)
,
N. Nighoghossian
(14, 15)
,
S. Pedraza
(16)
,
J. Puig
(16)
,
C. Z. Simonsen
(17)
,
V. Thijs
(18, 19)
,
A. Wouters
(10, 11, 12)
,
C. Gerloff
(1)
,
G. Thomalla
(1)
,
B. Cheng
(1)
1
UKE -
Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg]
2 HCL - Hospices Civils de Lyon
3 LBBE - Laboratoire de Biométrie et Biologie Evolutive - UMR 5558
4 UCBL - Université Claude Bernard Lyon 1
5 Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]
6 Klinik für Neurologie
7 DZNE - German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen
8 DZHK (German Centre for Cardiovascular Research), Partner site Heidelberg/Mannheim, Heidelberg
9 Neuroscience Research Center and Cluster of Excellence NeuroCure
10 University Hospitals Leuven [Leuven]
11 KU Leuven - Catholic University of Leuven = Katholieke Universiteit Leuven
12 Campus Gasthuisberg
13 University of Glasgow
14 CarMeN - Cardiovasculaire, métabolisme, diabétologie et nutrition
15 CREATIS - Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé
16 IDIBGI - Girona Biomedical Research Institute [Girona, Spain]
17 Aarhus University Hospital
18 Austin Health
19 University of Melbourne
2 HCL - Hospices Civils de Lyon
3 LBBE - Laboratoire de Biométrie et Biologie Evolutive - UMR 5558
4 UCBL - Université Claude Bernard Lyon 1
5 Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]
6 Klinik für Neurologie
7 DZNE - German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen
8 DZHK (German Centre for Cardiovascular Research), Partner site Heidelberg/Mannheim, Heidelberg
9 Neuroscience Research Center and Cluster of Excellence NeuroCure
10 University Hospitals Leuven [Leuven]
11 KU Leuven - Catholic University of Leuven = Katholieke Universiteit Leuven
12 Campus Gasthuisberg
13 University of Glasgow
14 CarMeN - Cardiovasculaire, métabolisme, diabétologie et nutrition
15 CREATIS - Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé
16 IDIBGI - Girona Biomedical Research Institute [Girona, Spain]
17 Aarhus University Hospital
18 Austin Health
19 University of Melbourne
M. Endres
- Fonction : Auteur
N. Nighoghossian
- Fonction : Auteur
- PersonId : 1144600
- ORCID : 0000-0003-0594-4409
Résumé
Thrombolysis with recombinant tissue plasminogen activator in acute ischemic stroke aims to restore compromised blood flow and prevent further neuronal damage. Despite the proven clinical efficacy of this treatment, little is known about the short-term effects of systemic thrombolysis on structural brain connectivity. In this secondary analysis of the WAKE-UP trial, we used MRI-derived measures of infarct size and estimated structural network disruption to establish that thrombolysis is associated not only with less infarct growth, but also with reduced loss of large-scale connectivity between grey-matter areas after stroke. In a causal mediation analysis, infarct growth mediated a non-significant 8.3% (CI(95%) [-8.0, 32.6]%) of the clinical effect of thrombolysis on functional outcome. The proportion mediated jointly through infarct growth and change of structural connectivity, especially in the border zone around the infarct core, however, was as high as 33.4% (CI(95%) [8.8, 77.4]%). Preservation of structural connectivity is thus an important determinant of treatment success and favourable functional outcome in addition to lesion volume. It might, in the future, serve as an imaging endpoint in clinical trials or as a target for therapeutic interventions.