Intravenous Thrombolysis in Unknown-Onset Stroke: Results From the Safe Implementation of Treatment in Stroke-International Stroke Thrombolysis Registry.
Stroke patients with unknown onset (UKO) are excluded from thrombolytic therapy. We aim to study the safety and efficacy of intravenous alteplase in ischemic stroke patients with UKO of symptoms compared with those treated within 4.5 hours in a large cohort.



Data were analyzed from 47 237 patients with acute ischemic stroke receiving intravenous tissue-type plasminogen activator in hospitals participating in the Safe Implementation of Treatment in Stroke-International Stroke Thrombolysis Registry between 2010 and 2014. Two groups were defined: (1) patients with UKO (n=502) and (2) patients treated within 4.5 hours of stroke onset (n=44 875). Outcome measures were symptomatic intracerebral hemorrhage per Safe Implementation of Treatment in Stroke on the 22 to 36 hours post-treatment neuroimaging and mortality and functional outcome assessed by the modified Rankin Scale at 3 months.



Patients in UKO group were significantly older, had more severe stroke at baseline, and longer door-to-needle times than patients in the ≤4.5 hours group. Logistic regression showed similar risk of symptomatic intracerebral hemorrhage (adjusted odds ratio, 1.09; 95% confidence interval, 0.44-2.67) and no significant differences in functional independency (modified Rankin Scale score of 0-2; adjusted odds ratio, 0.79; 95% confidence interval, 0.56-1.10), but higher mortality (adjusted odds ratio, 1.58; 95% confidence interval, 1.04-2.41) in the UKO group compared with the ≤4.5 hours group. Patients treated within 4.5 hours showed reduced disability over the entire range of modified Rankin Scale compared with the UKO group (common adjusted odds ratio, 1.29; 95% confidence interval, 1.01-1.65).



Our data suggest no excess risk of symptomatic intracerebral hemorrhage but increased mortality and reduced favorable outcome in patients with UKO stroke compared with patients treated within the approved time window.
From the Department of Neurosciences, University Hospital Germans Trias i Pujol, Badalona, Spain (L.D., M.L., M.M., A.D.); Karolinska University Hospital, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden (N.A.); Department of Neurology, Center for Clinical Neurosciences, University Medical Center Hamburg-Eppendorf, Germany (G.T.); Department of Neurology, University Hospital Center Zagreb, Croatia (B.M.); Department of Stroke Medicine, Morriston Hospital, Swansea, United Kingdom (M.W.); and Department of Neurology, Motol University Hospital, Charles University, Prague, Czech Republic (A.T.). lauritadb@yahoo.es.
Laura
L
Dorado
From the Department of Neurosciences, University Hospital Germans Trias i Pujol, Badalona, Spain (L.D., M.L., M.M., A.D.); Karolinska University Hospital, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden (N.A.); Department of Neurology, Center for Clinical Neurosciences, University Medical Center Hamburg-Eppendorf, Germany (G.T.); Department of Neurology, University Hospital Center Zagreb, Croatia (B.M.); Department of Stroke Medicine, Morriston Hospital, Swansea, United Kingdom (M.W.); and Department of Neurology, Motol University Hospital, Charles University, Prague, Czech Republic (A.T.).
Niaz
N
Ahmed
From the Department of Neurosciences, University Hospital Germans Trias i Pujol, Badalona, Spain (L.D., M.L., M.M., A.D.); Karolinska University Hospital, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden (N.A.); Department of Neurology, Center for Clinical Neurosciences, University Medical Center Hamburg-Eppendorf, Germany (G.T.); Department of Neurology, University Hospital Center Zagreb, Croatia (B.M.); Department of Stroke Medicine, Morriston Hospital, Swansea, United Kingdom (M.W.); and Department of Neurology, Motol University Hospital, Charles University, Prague, Czech Republic (A.T.).
Götz
G
Thomalla
From the Department of Neurosciences, University Hospital Germans Trias i Pujol, Badalona, Spain (L.D., M.L., M.M., A.D.); Karolinska University Hospital, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden (N.A.); Department of Neurology, Center for Clinical Neurosciences, University Medical Center Hamburg-Eppendorf, Germany (G.T.); Department of Neurology, University Hospital Center Zagreb, Croatia (B.M.); Department of Stroke Medicine, Morriston Hospital, Swansea, United Kingdom (M.W.); and Department of Neurology, Motol University Hospital, Charles University, Prague, Czech Republic (A.T.).
Manuel
M
Lozano
From the Department of Neurosciences, University Hospital Germans Trias i Pujol, Badalona, Spain (L.D., M.L., M.M., A.D.); Karolinska University Hospital, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden (N.A.); Department of Neurology, Center for Clinical Neurosciences, University Medical Center Hamburg-Eppendorf, Germany (G.T.); Department of Neurology, University Hospital Center Zagreb, Croatia (B.M.); Department of Stroke Medicine, Morriston Hospital, Swansea, United Kingdom (M.W.); and Department of Neurology, Motol University Hospital, Charles University, Prague, Czech Republic (A.T.).
Branko
B
Malojcic
From the Department of Neurosciences, University Hospital Germans Trias i Pujol, Badalona, Spain (L.D., M.L., M.M., A.D.); Karolinska University Hospital, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden (N.A.); Department of Neurology, Center for Clinical Neurosciences, University Medical Center Hamburg-Eppendorf, Germany (G.T.); Department of Neurology, University Hospital Center Zagreb, Croatia (B.M.); Department of Stroke Medicine, Morriston Hospital, Swansea, United Kingdom (M.W.); and Department of Neurology, Motol University Hospital, Charles University, Prague, Czech Republic (A.T.).
Mushtaq
M
Wani
From the Department of Neurosciences, University Hospital Germans Trias i Pujol, Badalona, Spain (L.D., M.L., M.M., A.D.); Karolinska University Hospital, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden (N.A.); Department of Neurology, Center for Clinical Neurosciences, University Medical Center Hamburg-Eppendorf, Germany (G.T.); Department of Neurology, University Hospital Center Zagreb, Croatia (B.M.); Department of Stroke Medicine, Morriston Hospital, Swansea, United Kingdom (M.W.); and Department of Neurology, Motol University Hospital, Charles University, Prague, Czech Republic (A.T.).
Mònica
M
Millán
From the Department of Neurosciences, University Hospital Germans Trias i Pujol, Badalona, Spain (L.D., M.L., M.M., A.D.); Karolinska University Hospital, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden (N.A.); Department of Neurology, Center for Clinical Neurosciences, University Medical Center Hamburg-Eppendorf, Germany (G.T.); Department of Neurology, University Hospital Center Zagreb, Croatia (B.M.); Department of Stroke Medicine, Morriston Hospital, Swansea, United Kingdom (M.W.); and Department of Neurology, Motol University Hospital, Charles University, Prague, Czech Republic (A.T.).
Ales
A
Tomek
From the Department of Neurosciences, University Hospital Germans Trias i Pujol, Badalona, Spain (L.D., M.L., M.M., A.D.); Karolinska University Hospital, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden (N.A.); Department of Neurology, Center for Clinical Neurosciences, University Medical Center Hamburg-Eppendorf, Germany (G.T.); Department of Neurology, University Hospital Center Zagreb, Croatia (B.M.); Department of Stroke Medicine, Morriston Hospital, Swansea, United Kingdom (M.W.); and Department of Neurology, Motol University Hospital, Charles University, Prague, Czech Republic (A.T.).
Antoni
A
Dávalos
D061605:Administration, Intravenous; D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000188:drug therapy*; D002543:Cerebral Hemorrhage / Q000209:etiology; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012042:Registries; D020521:Stroke / Q000188:drug therapy*; D015912:Thrombolytic Therapy / Q000379:methods; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator
alteplase; cerebral hemorrhage; neuroimaging; prognosis; safety; stroke