title: Reperfusion therapy in unclear-onset stroke based on MRI evaluation (RESTORE): a prospective multicenter study.
abstract: OBJECTIVE
  Unclear-onset strokes are generally excluded from time-based thrombolytic therapy. We examined the safety and feasibility of magnetic resonance imaging-based reperfusion therapy in unclear-onset stroke.
  
  
  METHODS
  This prospective, multicenter, single-arm study screened consecutive unclear-onset stroke patients within 6 hours of symptom detection. Patients with perfusion-diffusion mismatch>20% and negative or subtle fluid-attenuated inversion recovery changes were treated with intravenous tissue plasminogen activator, intra-arterial therapy, or a combination. The safety outcome was symptomatic intracranial hemorrhage within 48 hours after treatment. The primary efficacy outcome was a 3-month modified Rankin Scale score of 0 to 2. Controls were untreated unclear-onset stroke patients prospectively captured in stroke registries.
  
  
  RESULTS
  Of 430 unclear-onset stroke patients, 83 (19.3%) received reperfusion therapy (mean age, 67.5±10.4 years; males, 66.3%; median baseline National Institutes of Health Stroke Scale, 14). Symptomatic intracranial hemorrhage with any neurological decline developed in 5 patients (6.0%). Symptomatic intracranial hemorrhage with National Institutes of Health Stroke Scale worsening ≥4 developed in 3 patients (3.6%). Thirty-seven patients (44.6%) achieved modified Rankin Scale score of 0 to 2, and 24 (28.9%) had modified Rankin Scale score of 0 to 1. Female, baseline National Institutes of Health Stroke Scale score, no immediate or early recanalization, and more white blood cells were independent predictors of poor outcome. Compared with untreated controls, the treated group was significantly associated with good outcomes of modified Rankin Scale score of 0 to 2 after adjusting for age, sex, and baseline National Institutes of Health Stroke Scale in logistic regression analysis (odds ratio, 2.25; 95% CI, 1.14-4.49).
  
  
  CONCLUSIONS
  In unclear-onset stroke patients, magnetic resonance imaging-based reperfusion therapy was feasible and safe. Randomized controlled trials are warranted to confirm the benefit of reperfusion therapy for unclear-onset stroke.
authors.affiliation: Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, and Eulji General Hospital, 88 Olympic-ro, 43-gil, Songpa-gu, Seoul 138-736, South Korea. dwkang@amc.seoul.kr
authors.forename: Dong-Wha
authors.initials: DW
authors.lastname: Kang
authors.forename: Sung-Il
authors.initials: SI
authors.lastname: Sohn
authors.forename: Keun-Sik
authors.initials: KS
authors.lastname: Hong
authors.forename: Kyung-Ho
authors.initials: KH
authors.lastname: Yu
authors.forename: Yang-Ha
authors.initials: YH
authors.lastname: Hwang
authors.forename: Moon-Ku
authors.initials: MK
authors.lastname: Han
authors.forename: Jun
authors.initials: J
authors.lastname: Lee
authors.forename: Jong-Moo
authors.initials: JM
authors.lastname: Park
authors.forename: A-Hyun
authors.initials: AH
authors.lastname: Cho
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Dong-Eog
authors.initials: DE
authors.lastname: Kim
authors.forename: Yong-Jin
authors.initials: YJ
authors.lastname: Cho
authors.forename: Jaseong
authors.initials: J
authors.lastname: Koo
authors.forename: Sung-Cheol
authors.initials: SC
authors.lastname: Yun
authors.forename: Sun U
authors.initials: SU
authors.lastname: Kwon
authors.forename: Hee-Joon
authors.initials: HJ
authors.lastname: Bae
authors.forename: Jong S
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000368:Aged; D002548:Cerebral Revascularization / Q000009:adverse effects / Q000379:methods*; D005240:Feasibility Studies; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology*; D015912:Thrombolytic Therapy / Q000009:adverse effects / Q000379:methods*; D061665:Time-to-Treatment; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage; D016896:Treatment Outcome; D035501:Uncertainty
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator