Prospective study on the mismatch concept in acute stroke patients within the first 24 h after symptom onset - 1000Plus study.
BACKGROUND
The mismatch between diffusion weighted imaging (DWI) lesion and perfusion imaging (PI) deficit volumes has been used as a surrogate of ischemic penumbra. This pathophysiology-orientated patient selection criterion for acute stroke treatment may have the potential to replace a fixed time window. Two recent trials - DEFUSE and EPITHET - investigated the mismatch concept in a multicenter prospective approach. Both studies randomized highly selected patients (n = 74/n = 100) and therefore confirmation in a large consecutive cohort is desirable. We here present a single-center approach with a 3T MR tomograph next door to the stroke unit, serving as a bridge from the ER to the stroke unit to screen all TIA and stroke patients. Our primary hypothesis is that the prognostic value of the mismatch concept is depending on the vessel status. Primary endpoint of the study is infarct growth determined by imaging, secondary endpoints are neurological deficit on day 5-7 and functional outcome after 3 months.


METHODS
1000Plus is a prospective, single centre observational study with 1200 patients to be recruited. All patients admitted to the ER with the clinical diagnosis of an acute cerebrovascular event within 24 hours after symptom onset are screened. Examinations are performed on day 1, 2 and 5-7 with neurological examination including National Institute of Health Stroke Scale (NIHSS) scoring and stroke MRI including T2*, DWI, TOF-MRA, FLAIR and PI. PI is conducted as dynamic susceptibility-enhanced contrast imaging with a fixed dosage of 5 ml 1 M Gadobutrol. For post-processing of PI, mean transit time (MTT) parametric images are determined by deconvolution of the arterial input function (AIF) which is automatically identified. Lesion volumes and mismatch are measured and calculated by using the perfusion mismatch analyzer (PMA) software from ASIST-Japan. Primary endpoint is the change of infarct size between baseline examination and day 5-7 follow up.


CONCLUSIONS
The aim of this study is to describe the incidence of mismatch and the predictive value of PI for final lesion size and functional outcome depending on delay of imaging and vascular recanalization. It is crucial to standardize PI for future randomized clinical trials as for individual therapeutic decisions and we expect to contribute to this challenging task.


BACKGROUND
clinicaltrials.gov NCT00715533.
Hotter
Benjamin
B
Center for Stroke Research Berlin, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. benjamin.hotter@charite.de
Pittl
Sandra
S
Ebinger
Martin
M
Oepen
Gabriele
G
Jegzentis
Kati
K
Kudo
Kohsuke
K
Rozanski
Michal
M
Schmidt
Wolf U
WU
Brunecker
Peter
P
Xu
Chao
C
Martus
Peter
P
Endres
Matthias
M
Jungehülsing
Gerhard J
GJ
Villringer
Arno
A
Fiebach
Jochen B
JB
D000328:Adult; D000368:Aged; D001921:Brain / Q000473:pathology*; D002560:Cerebrovascular Circulation; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods; D018810:Magnetic Resonance Angiography / Q000379:methods; D008297:Male; D008875:Middle Aged; D019370:Observation; D010477:Perfusion; D011237:Predictive Value of Tests; D011446:Prospective Studies; D020521:Stroke / Q000175:diagnosis*; D013997:Time Factors; D055815:Young Adult