Evaluation of Early Reperfusion Criteria in Acute Ischemic Stroke.
OBJECTIVE
Though still debated, early reperfusion is increasingly used as a biomarker for clinical outcome. However, the lack of a standard definition hinders the assessment of reperfusion therapies and study comparisons. The objective was to determine the optimal early reperfusion criteria that predicts clinical outcome in ischemic stroke.


METHODS
Early reperfusion was assessed voxel-wise in 57 patients within 6 hours of symptom onset. The performance of the time to peak (TTP), the mean transit time (MTT), and the time to maximum of residue function (Tmax ) at various delays thresholds in predicting the neurological response (based on the National Institutes of Health Stroke Scale) and the functional outcome (modified Rankin scale ≤1) at 1 month were compared. A receiver operating characteristics (ROC) analysis determined the optimal extent of reperfusion. A novel unsupervised classification of reperfusion using group-based trajectory modeling (GBTM) was evaluated.


RESULTS
MTT had a lower performance than TTP and Tmax in predicting the neurological response (P = .008 vs. TTP and P = .006 vs. Tmax ) or the functional outcome (P = .0006 vs. TTP; P = .002 vs. Tmax ). No delay threshold had a significantly higher predictive value than another. The optimal percentage of reperfusion was dependent on the outcome scale (P < .001). The GBTM-based classification of reperfusion was closely associated with the clinical outcome and had a similar accuracy compared to ROC-based classification.


CONCLUSIONS
TTP and Tmax should be preferred to MTT in defining early reperfusion. GBTM provided a clinically relevant reperfusion classification that does not require prespecified delay thresholds or clinical outcomes.
Service de Biostatistique, Hospices Civils de Lyon, Lyon, France, Equipe Biostatistique Santé CNRS UMR 5558, Villeurbanne, France; Université Lyon I, Lyon, France.
Brice
B
Ozenne
Department of Stroke Medicine and Department of Neuroradiology, Université Lyon 1; CREATIS, CNRS UMR 5220-INSERM U1044, INSA-Lyon; Hospices Civils de Lyon, Lyon, France.
Tae-Hee
TH
Cho
Center of Functionally Integrative Neuroscience, Aarhus University, Aarhus, Denmark.|Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Irene Klaerke
IK
Mikkelsen
Service de Biostatistique, Hospices Civils de Lyon, Lyon, France, Equipe Biostatistique Santé CNRS UMR 5558, Villeurbanne, France; Université Lyon I, Lyon, France.
Marc
M
Hermier
Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Lars
L
Ribe
Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Götz
G
Thomalla
Department of Radiology (IDI), Girona Biomedical Research Institute (IDIBGI), Hospital Universitari de Girona Dr Josep Trueta, Girona, Spain.
Salvador
S
Pedraza
INSERM U894, Hôpital Sainte-Anne, Université Paris Descartes, Sorbonne Paris Cité, France.
Jean-Claude
JC
Baron
Service de Biostatistique, Hospices Civils de Lyon, Lyon, France, Equipe Biostatistique Santé CNRS UMR 5558, Villeurbanne, France; Université Lyon I, Lyon, France.
Pascal
P
Roy
Department of Stroke Medicine and Department of Neuroradiology, Université Lyon 1; CREATIS, CNRS UMR 5220-INSERM U1044, INSA-Lyon; Hospices Civils de Lyon, Lyon, France.
Yves
Y
Berthezène
Department of Stroke Medicine and Department of Neuroradiology, Université Lyon 1; CREATIS, CNRS UMR 5220-INSERM U1044, INSA-Lyon; Hospices Civils de Lyon, Lyon, France.
Norbert
N
Nighoghossian
Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Leif
L
Østergaard
Service de Biostatistique, Hospices Civils de Lyon, Lyon, France, Equipe Biostatistique Santé CNRS UMR 5558, Villeurbanne, France; Université Lyon I, Lyon, France.
Delphine
D
Maucort-Boulch
D000368:Aged; D002545:Brain Ischemia / Q000000981:diagnostic imaging* / Q000188:drug therapy; D002560:Cerebrovascular Circulation / Q000502:physiology*; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006801:Humans; D018810:Magnetic Resonance Angiography; D008279:Magnetic Resonance Imaging; D008297:Male; D015424:Reperfusion; D020521:Stroke / Q000000981:diagnostic imaging* / Q000188:drug therapy; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use; D016896:Treatment Outcome
D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator
Acute stroke imaging; ROC analysis; group-based trajectory modeling (GBTM); perfusion-weighted imaging (PWI); reperfusion