title: Safety and efficacy of intravenous tissue plasminogen activator stroke treatment in the 3- to 6-hour window using multimodal transcranial Doppler/MRI selection protocol.
abstract: BACKGROUND
  Growing data point toward intravenous tissue plasminogen activator (tPA) benefit after 3 hours in selected stroke patients. We aim to study safety and efficacy of tPA treatment in the 3- to 6-hour window using multimodal transcranial Doppler (TCD)/MRI selection criteria.
  
  
  METHODS
  We studied patients with acute middle cerebral artery (MCA) occlusion. Patients within 0 to 3 hours from symptom onset (A) were treated according to standard computed tomography criteria. Treatment within 3 to 6 hours (B) was decided according to TCD/MRI protocol. Continuous TCD assessed clot location and recanalization. National Institutes of Health Stroke Scale (NIHSS) at 24 hours assessed neurological improvement/worsening and modified Rankin score <3 functional independence at third month.
  
  
  RESULTS
  Of 135 patients, 56 were in the 3- to 6-hour window. Only 13 (23%) patients within 3 to 6 hours did not meet MRI inclusion criteria. Finally, 122 patients were treated with tPA: A, 79 (65%); B, 43 (35%). Median time to treatment was: A, 136 minutes (range 60 to 180); B, 223 (185 to 360). There were no differences in demographic parameters, baseline NIHSS (A, 17; B, 17; P=0.89), and occlusion location (proximal MCA A, 65.8%; B, 74.4%; P=0.28). Recanalization rates at 2 hours were similar (A, 49.3%; B, 55.2%; P=0.33), as were hemorrhagic transformation rates (asymptomatic: A, 18.7%, B, 26.6%, P=0.43; symptomatic: A, 3.75%, B, 2.38%, P=0.66). Improvement at discharge was similar in both groups (NIHSS dropped 6.3 points [A] versus 6.1 [B]; P=0.86). However, the number of patients who benefited from treatment was slightly higher in the 3- to 6-hour group (A, 58.2%; B, 76.2%; P=0.05), whereas the same rate of patients worsened (A, 11.4%; B, 7.1%; P=0.46). At 3 months, the rate of independent patients was: A, 42% versus B, 38% (P=0.74).
  
  
  CONCLUSIONS
  tPA treatment can be safely and effectively extended to the 3- to 6-hour window using TCD/MRI selection criteria. Not using these criteria in the 3- to 6-hour window avoids potentially effective treatment in a high rate of patients.
authors.affiliation: Unitat Neurovascular, Hospital Vall d'Hebron, Universitat Autonoma de Barcelona, Spain. marcriboj@hotmail.com
authors.forename: Marc
authors.initials: M
authors.lastname: Ribo
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Molina
authors.forename: Alex
authors.initials: A
authors.lastname: Rovira
authors.forename: Manuel
authors.initials: M
authors.lastname: Quintana
authors.forename: Pilar
authors.initials: P
authors.lastname: Delgado
authors.forename: Joan
authors.initials: J
authors.lastname: Montaner
authors.forename: Elisenda
authors.initials: E
authors.lastname: Grivé
authors.forename: Juan F
authors.initials: JF
authors.lastname: Arenillas
authors.forename: José
authors.initials: J
authors.lastname: Alvarez-Sabín
mesh_terms: D000208:Acute Disease; D000368:Aged; D005260:Female; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D011446:Prospective Studies; D012449:Safety; D020521:Stroke / Q000188:drug therapy*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D016896:Treatment Outcome; D017585:Ultrasonography, Doppler, Transcranial / Q000379:methods*
chemical_list: D010959:Tissue Plasminogen Activator