title: Validation of FLAIR hyperintense lesions as imaging biomarkers to predict the outcome of acute stroke after intra-arterial thrombolysis following intravenous tissue plasminogen activator.
abstract: BACKGROUND
  Intravenous tissue plasminogen activator (tPA) given within 4.5 h of symptom onset is accepted as the standard treatment of ischemic stroke. Persistent occlusion of cerebral arteries despite intravenous thrombolysis and unremitting neurologic deficits lead us to consider additional intra-arterial approaches. The aim of this study was to elucidate the potential of fluid-attenuated inversion recovery (FLAIR) MRI performed during or immediately after intravenous thrombolysis for predicting clinical outcomes of subsequent intra-arterial thrombolysis.
  
  
  METHODS
  With a prospective stroke registry database of patients hospitalized in our institution from January 2004 to February 2010, we identified ischemic stroke patients with the following conditions: (1) presentation within 2.5 h of onset, (2) treated with intravenous tPA based on brain CT, (3) persistent occlusion on subsequent MRI/MR angiography, including a FLAIR sequence, and (4) eventually treated with intra-arterial thrombolysis. Demographic, clinical and laboratory findings including initial National Institutes of Health Stroke Scale (NIHSS), follow-up NIHSS at the 7th day or discharge, modified Rankin scale (mRS) score at 3 months, and symptomatic hemorrhagic transformation were captured. FLAIR images were reviewed by 2 investigators blinded to clinical information independently and dichotomized into the absence and presence of FLAIR change within the diffusion-restriction lesions.
  
  
  RESULTS
  Of the 57 patients who met these conditions, FLAIR-hyperintense lesions (FHL) were observed in 32 (56.1%). The FHL-negative group was 69.1 ± 12.1 years old on average and the FHL-positive group 67.3 ± 11.0 years old. In both groups, hypertension was the most common vascular risk factor, cardioembolic stroke was the most common subtype, and distal middle cerebral artery was the most common site of occlusion. The incidence of symptomatic hemorrhagic transformation was 4.0% in the FHL-negative group and 9.4% in the FHL-positive group (p = 0.62). NIHSS scores of 0-1 on the 7th day of hospitalization or at discharge were observed in 36% of the FHL-negative group and in 9.4% of the FHL-positive group; mRS scores of 0-1 at 3 months was 32% in the FHL-negative group and 21% in the FHL-positive group. An ordinal logistic regression analysis showed that the presence of FHL was associated with higher 7-day NIHSS scores (adjusted for relevant covariates) but not with higher 3-month mRS scores.
  
  
  CONCLUSIONS
  This study suggests that the FHL might be used as imaging biomarker to predict outcomes for additional intra-arterial thrombolysis in patients treated with intravenous tPA.
authors.affiliation: Department of Neurology, Stroke Center, Seoul National University Bundang Hospital, College of Medicine, Seoul, Korea.
authors.forename: Jong-Won
authors.initials: JW
authors.lastname: Chung
authors.forename: Kyeong Joon
authors.initials: KJ
authors.lastname: Kim
authors.forename: Won-Young
authors.initials: WY
authors.lastname: Noh
authors.forename: Myung Suk
authors.initials: MS
authors.lastname: Jang
authors.forename: Mi Hwa
authors.initials: MH
authors.lastname: Yang
authors.forename: Moon-Ku
authors.initials: MK
authors.lastname: Han
authors.forename: O-Ki
authors.initials: OK
authors.lastname: Kwon
authors.forename: Cheolkyu
authors.initials: C
authors.lastname: Jung
authors.forename: Jae Hyoung
authors.initials: JH
authors.lastname: Kim
authors.forename: Chang Wan
authors.initials: CW
authors.lastname: Oh
authors.forename: Ji Sung
authors.initials: JS
authors.lastname: Lee
authors.forename: Juneyoung
authors.initials: J
authors.lastname: Lee
authors.forename: Hee-Joon
authors.initials: HJ
authors.lastname: Bae
mesh_terms: D000077284:Abciximab; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000453:epidemiology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy; D003131:Combined Modality Therapy; D015897:Comorbidity; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000627:therapeutic use*; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D020300:Intracranial Hemorrhages / Q000453:epidemiology / Q000209:etiology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D061185:Mechanical Thrombolysis; D008875:Middle Aged; D059906:Neuroimaging / Q000379:methods / Q000592:standards*; D011379:Prognosis; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D016037:Single-Blind Method; D015912:Thrombolytic Therapy / Q000379:methods*; D000077466:Tirofiban; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D014443:Tyrosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D005343:Fibrinolytic Agents; D007140:Immunoglobulin Fab Fragments; D014443:Tyrosine; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D000077466:Tirofiban; D000077284:Abciximab