title: Refining the definition of the malignant profile: insights from the DEFUSE-EPITHET pooled data set.
abstract: OBJECTIVE
  To refine the definition of the malignant magnetic resonance imaging profile in acute stroke patients using baseline diffusion-weighted magnetic resonance imaging (DWI) and perfusion-weighted magnetic resonance imaging (PWI) findings from the pooled DEFUSE/EPITHET database.
  
  
  METHODS
  Patients presenting with acute stroke within 3 to 6 hours from symptom onset were treated with tissue plasminogen activator or placebo. Baseline and follow-up DWI and PWI images from both studies were reprocessed using the same software program. A receiver operating characteristic curve analysis was used to identify Tmax and DWI volumes that optimally predicted poor outcomes (modified Rankin Scale 5-6) at 90 days in patients who achieved reperfusion.
  
  
  RESULTS
  Sixty-five patients achieved reperfusion and 46 did not reperfuse. Receiver operating characteristic analysis identified a PWI (Tmax>8 s) volume of >85 mL as the optimal definition of the malignant profile. Eighty-nine percent of malignant profile patients had poor outcome with reperfusion versus 39% of patients without reperfusion (P=0.02). Parenchymal hematomas occurred more frequently in malignant profile patients who experienced reperfusion versus no reperfusion (67% versus 11%, P<0.01). DWI analysis identified a volume of 80 mL as the best DWI threshold, but this definition was less sensitive than were PWI-based definitions.
  
  
  CONCLUSIONS
  Stroke patients likely to suffer parenchymal hemorrhages and poor outcomes following reperfusion can be identified from baseline magnetic resonance imaging findings. The current analysis demonstrates that a PWI threshold (Tmax>8 s) of approximately 100 mL is appropriate for identifying these patients. Exclusion of malignant profile patients from reperfusion therapies may substantially improve the efficacy and safety of reperfusion therapies. Clinical Trial Registration Information- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00238537.
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford Stroke Center, 780 Welch Road, Suite 205, Stanford, Stanford, CA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Mlynash
authors.forename: Maarten G
authors.initials: MG
authors.lastname: Lansberg
authors.forename: Deidre A
authors.initials: DA
authors.lastname: De Silva
authors.forename: Jun
authors.initials: J
authors.lastname: Lee
authors.forename: Soren
authors.initials: S
authors.lastname: Christensen
authors.forename: Matus
authors.initials: M
authors.lastname: Straka
authors.forename: Bruce C V
authors.initials: BC
authors.lastname: Campbell
authors.forename: Roland
authors.initials: R
authors.lastname: Bammer
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Olivot
authors.forename: Patricia
authors.initials: P
authors.lastname: Desmond
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Donnan
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Davis
authors.forename: Gregory W
authors.initials: GW
authors.lastname: Albers
mesh_terms: D000368:Aged; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006801:Humans; D020300:Intracranial Hemorrhages / Q000188:drug therapy / Q000453:epidemiology* / Q000473:pathology*; D018810:Magnetic Resonance Angiography; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012372:ROC Curve; D020521:Stroke / Q000150:complications* / Q000188:drug therapy / Q000473:pathology*; D015912:Thrombolytic Therapy; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator