title: Repeated Intravenous Thrombolysis for Early Recurrent Stroke: Challenging the Exclusion Criterion.
abstract: Intravenous thrombolysis (IVT) within 4.5 hours from symptom onset improves functional outcome in patients with acute ischemic stroke. Its use in patients with previous stroke within the preceding 3 months is contraindicated because of the assumed higher risk of intracranial hemorrhage. In addition, tissue-type plasminogen activator may itself promote neurotoxicity and blood-brain barrier disruption. However, safety and effectiveness of repeated IVT is essentially unknown in patients with early (<3 months) recurrent stroke (ERS), because they were excluded from thrombolysis trials. This article reports the largest case series of repeated IVT in ERS.
  
  
  
  We reviewed databases of prospectively collected patient data of 8 European stroke centers for the presence of patients with ERS, who received IVT for both the index stroke and ERS. Demographics, clinical and radiological data, bleeding complications, and functional outcome were analyzed.
  
  
  
  We identified 19 subjects with repeated IVT in ERS. Mean age was 68±12 years, and 37% of them were female. Median interthrombolysis interval was 30 days (interquartile range, 13-50). Functional independence (modified Rankin scale score ≤2) was achieved in 79% of patients after the first and in 47.4% after repeated IV tissue-type plasminogen activator, respectively. There was no symptomatic intracranial hemorrhage. Median final infarct volume after the first IVT was 1.5 cm(3) (interquartile range, 0.5-3.1).
  
  
  
  Patients with small infarct volumes and robust clinical improvement might be considered for repeated IVT within 3 months. Studies following strict protocols and larger registries incorporating these patients might serve to identify selection criteria for the safe use of repeated IVT in ERS.
authors.affiliation: From the Department of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland (T.K., K.N.); Inselspital, University Hospital and University of Bern, Bern, Switzerland (M.-L.M., M.R.H., H.S.); Hirslanden Hospital Zurich, Zurich, Switzerland (R.W.B.); University Hospital Zurich, Zurich, Switzerland (A.L.); Cantonal Hospital Lucerne, Lucerne, Switzerland (S.B.); University Hospital Basel, Basel, Switzerland (C.T., S.T.E.); Universitätsklinikum Erlangen, Erlangen, Germany (N.K., M.K.); Helsinki University Central Hospital, Helsinki, Finland (S.C., T.T.); Sahlgrenska University Hospital, Gothenburg, Sweden (T.T.); Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (T.T.); and University Hospital Lausanne CHUV, Lausanne, Switzerland (P.M.).
authors.forename: Timo
authors.initials: T
authors.lastname: Kahles
authors.affiliation: From the Department of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland (T.K., K.N.); Inselspital, University Hospital and University of Bern, Bern, Switzerland (M.-L.M., M.R.H., H.S.); Hirslanden Hospital Zurich, Zurich, Switzerland (R.W.B.); University Hospital Zurich, Zurich, Switzerland (A.L.); Cantonal Hospital Lucerne, Lucerne, Switzerland (S.B.); University Hospital Basel, Basel, Switzerland (C.T., S.T.E.); Universitätsklinikum Erlangen, Erlangen, Germany (N.K., M.K.); Helsinki University Central Hospital, Helsinki, Finland (S.C., T.T.); Sahlgrenska University Hospital, Gothenburg, Sweden (T.T.); Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (T.T.); and University Hospital Lausanne CHUV, Lausanne, Switzerland (P.M.).
authors.forename: Marie-Luise
authors.initials: ML
authors.lastname: Mono
authors.affiliation: From the Department of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland (T.K., K.N.); Inselspital, University Hospital and University of Bern, Bern, Switzerland (M.-L.M., M.R.H., H.S.); Hirslanden Hospital Zurich, Zurich, Switzerland (R.W.B.); University Hospital Zurich, Zurich, Switzerland (A.L.); Cantonal Hospital Lucerne, Lucerne, Switzerland (S.B.); University Hospital Basel, Basel, Switzerland (C.T., S.T.E.); Universitätsklinikum Erlangen, Erlangen, Germany (N.K., M.K.); Helsinki University Central Hospital, Helsinki, Finland (S.C., T.T.); Sahlgrenska University Hospital, Gothenburg, Sweden (T.T.); Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (T.T.); and University Hospital Lausanne CHUV, Lausanne, Switzerland (P.M.).
authors.forename: Mirjam Rachel
authors.initials: MR
authors.lastname: Heldner
authors.affiliation: From the Department of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland (T.K., K.N.); Inselspital, University Hospital and University of Bern, Bern, Switzerland (M.-L.M., M.R.H., H.S.); Hirslanden Hospital Zurich, Zurich, Switzerland (R.W.B.); University Hospital Zurich, Zurich, Switzerland (A.L.); Cantonal Hospital Lucerne, Lucerne, Switzerland (S.B.); University Hospital Basel, Basel, Switzerland (C.T., S.T.E.); Universitätsklinikum Erlangen, Erlangen, Germany (N.K., M.K.); Helsinki University Central Hospital, Helsinki, Finland (S.C., T.T.); Sahlgrenska University Hospital, Gothenburg, Sweden (T.T.); Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (T.T.); and University Hospital Lausanne CHUV, Lausanne, Switzerland (P.M.).
authors.forename: Ralf Werner
authors.initials: RW
authors.lastname: Baumgartner
authors.affiliation: From the Department of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland (T.K., K.N.); Inselspital, University Hospital and University of Bern, Bern, Switzerland (M.-L.M., M.R.H., H.S.); Hirslanden Hospital Zurich, Zurich, Switzerland (R.W.B.); University Hospital Zurich, Zurich, Switzerland (A.L.); Cantonal Hospital Lucerne, Lucerne, Switzerland (S.B.); University Hospital Basel, Basel, Switzerland (C.T., S.T.E.); Universitätsklinikum Erlangen, Erlangen, Germany (N.K., M.K.); Helsinki University Central Hospital, Helsinki, Finland (S.C., T.T.); Sahlgrenska University Hospital, Gothenburg, Sweden (T.T.); Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (T.T.); and University Hospital Lausanne CHUV, Lausanne, Switzerland (P.M.).
authors.forename: Hakan
authors.initials: H
authors.lastname: Sarikaya
authors.affiliation: From the Department of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland (T.K., K.N.); Inselspital, University Hospital and University of Bern, Bern, Switzerland (M.-L.M., M.R.H., H.S.); Hirslanden Hospital Zurich, Zurich, Switzerland (R.W.B.); University Hospital Zurich, Zurich, Switzerland (A.L.); Cantonal Hospital Lucerne, Lucerne, Switzerland (S.B.); University Hospital Basel, Basel, Switzerland (C.T., S.T.E.); Universitätsklinikum Erlangen, Erlangen, Germany (N.K., M.K.); Helsinki University Central Hospital, Helsinki, Finland (S.C., T.T.); Sahlgrenska University Hospital, Gothenburg, Sweden (T.T.); Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (T.T.); and University Hospital Lausanne CHUV, Lausanne, Switzerland (P.M.).
authors.forename: Andreas
authors.initials: A
authors.lastname: Luft
authors.affiliation: From the Department of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland (T.K., K.N.); Inselspital, University Hospital and University of Bern, Bern, Switzerland (M.-L.M., M.R.H., H.S.); Hirslanden Hospital Zurich, Zurich, Switzerland (R.W.B.); University Hospital Zurich, Zurich, Switzerland (A.L.); Cantonal Hospital Lucerne, Lucerne, Switzerland (S.B.); University Hospital Basel, Basel, Switzerland (C.T., S.T.E.); Universitätsklinikum Erlangen, Erlangen, Germany (N.K., M.K.); Helsinki University Central Hospital, Helsinki, Finland (S.C., T.T.); Sahlgrenska University Hospital, Gothenburg, Sweden (T.T.); Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (T.T.); and University Hospital Lausanne CHUV, Lausanne, Switzerland (P.M.).
authors.forename: Stephan
authors.initials: S
authors.lastname: Bohlhalter
authors.affiliation: From the Department of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland (T.K., K.N.); Inselspital, University Hospital and University of Bern, Bern, Switzerland (M.-L.M., M.R.H., H.S.); Hirslanden Hospital Zurich, Zurich, Switzerland (R.W.B.); University Hospital Zurich, Zurich, Switzerland (A.L.); Cantonal Hospital Lucerne, Lucerne, Switzerland (S.B.); University Hospital Basel, Basel, Switzerland (C.T., S.T.E.); Universitätsklinikum Erlangen, Erlangen, Germany (N.K., M.K.); Helsinki University Central Hospital, Helsinki, Finland (S.C., T.T.); Sahlgrenska University Hospital, Gothenburg, Sweden (T.T.); Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (T.T.); and University Hospital Lausanne CHUV, Lausanne, Switzerland (P.M.).
authors.forename: Christopher
authors.initials: C
authors.lastname: Traenka
authors.affiliation: From the Department of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland (T.K., K.N.); Inselspital, University Hospital and University of Bern, Bern, Switzerland (M.-L.M., M.R.H., H.S.); Hirslanden Hospital Zurich, Zurich, Switzerland (R.W.B.); University Hospital Zurich, Zurich, Switzerland (A.L.); Cantonal Hospital Lucerne, Lucerne, Switzerland (S.B.); University Hospital Basel, Basel, Switzerland (C.T., S.T.E.); Universitätsklinikum Erlangen, Erlangen, Germany (N.K., M.K.); Helsinki University Central Hospital, Helsinki, Finland (S.C., T.T.); Sahlgrenska University Hospital, Gothenburg, Sweden (T.T.); Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (T.T.); and University Hospital Lausanne CHUV, Lausanne, Switzerland (P.M.).
authors.forename: Stefan T
authors.initials: ST
authors.lastname: Engelter
authors.affiliation: From the Department of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland (T.K., K.N.); Inselspital, University Hospital and University of Bern, Bern, Switzerland (M.-L.M., M.R.H., H.S.); Hirslanden Hospital Zurich, Zurich, Switzerland (R.W.B.); University Hospital Zurich, Zurich, Switzerland (A.L.); Cantonal Hospital Lucerne, Lucerne, Switzerland (S.B.); University Hospital Basel, Basel, Switzerland (C.T., S.T.E.); Universitätsklinikum Erlangen, Erlangen, Germany (N.K., M.K.); Helsinki University Central Hospital, Helsinki, Finland (S.C., T.T.); Sahlgrenska University Hospital, Gothenburg, Sweden (T.T.); Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (T.T.); and University Hospital Lausanne CHUV, Lausanne, Switzerland (P.M.).
authors.forename: Natalia
authors.initials: N
authors.lastname: Kurka
authors.affiliation: From the Department of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland (T.K., K.N.); Inselspital, University Hospital and University of Bern, Bern, Switzerland (M.-L.M., M.R.H., H.S.); Hirslanden Hospital Zurich, Zurich, Switzerland (R.W.B.); University Hospital Zurich, Zurich, Switzerland (A.L.); Cantonal Hospital Lucerne, Lucerne, Switzerland (S.B.); University Hospital Basel, Basel, Switzerland (C.T., S.T.E.); Universitätsklinikum Erlangen, Erlangen, Germany (N.K., M.K.); Helsinki University Central Hospital, Helsinki, Finland (S.C., T.T.); Sahlgrenska University Hospital, Gothenburg, Sweden (T.T.); Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (T.T.); and University Hospital Lausanne CHUV, Lausanne, Switzerland (P.M.).
authors.forename: Martin
authors.initials: M
authors.lastname: Köhrmann
authors.affiliation: From the Department of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland (T.K., K.N.); Inselspital, University Hospital and University of Bern, Bern, Switzerland (M.-L.M., M.R.H., H.S.); Hirslanden Hospital Zurich, Zurich, Switzerland (R.W.B.); University Hospital Zurich, Zurich, Switzerland (A.L.); Cantonal Hospital Lucerne, Lucerne, Switzerland (S.B.); University Hospital Basel, Basel, Switzerland (C.T., S.T.E.); Universitätsklinikum Erlangen, Erlangen, Germany (N.K., M.K.); Helsinki University Central Hospital, Helsinki, Finland (S.C., T.T.); Sahlgrenska University Hospital, Gothenburg, Sweden (T.T.); Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (T.T.); and University Hospital Lausanne CHUV, Lausanne, Switzerland (P.M.).
authors.forename: Sami
authors.initials: S
authors.lastname: Curtze
authors.affiliation: From the Department of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland (T.K., K.N.); Inselspital, University Hospital and University of Bern, Bern, Switzerland (M.-L.M., M.R.H., H.S.); Hirslanden Hospital Zurich, Zurich, Switzerland (R.W.B.); University Hospital Zurich, Zurich, Switzerland (A.L.); Cantonal Hospital Lucerne, Lucerne, Switzerland (S.B.); University Hospital Basel, Basel, Switzerland (C.T., S.T.E.); Universitätsklinikum Erlangen, Erlangen, Germany (N.K., M.K.); Helsinki University Central Hospital, Helsinki, Finland (S.C., T.T.); Sahlgrenska University Hospital, Gothenburg, Sweden (T.T.); Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (T.T.); and University Hospital Lausanne CHUV, Lausanne, Switzerland (P.M.).
authors.forename: Patrik
authors.initials: P
authors.lastname: Michel
authors.affiliation: From the Department of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland (T.K., K.N.); Inselspital, University Hospital and University of Bern, Bern, Switzerland (M.-L.M., M.R.H., H.S.); Hirslanden Hospital Zurich, Zurich, Switzerland (R.W.B.); University Hospital Zurich, Zurich, Switzerland (A.L.); Cantonal Hospital Lucerne, Lucerne, Switzerland (S.B.); University Hospital Basel, Basel, Switzerland (C.T., S.T.E.); Universitätsklinikum Erlangen, Erlangen, Germany (N.K., M.K.); Helsinki University Central Hospital, Helsinki, Finland (S.C., T.T.); Sahlgrenska University Hospital, Gothenburg, Sweden (T.T.); Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (T.T.); and University Hospital Lausanne CHUV, Lausanne, Switzerland (P.M.).
authors.forename: Turgut
authors.initials: T
authors.lastname: Tatlisumak
authors.affiliation: From the Department of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland (T.K., K.N.); Inselspital, University Hospital and University of Bern, Bern, Switzerland (M.-L.M., M.R.H., H.S.); Hirslanden Hospital Zurich, Zurich, Switzerland (R.W.B.); University Hospital Zurich, Zurich, Switzerland (A.L.); Cantonal Hospital Lucerne, Lucerne, Switzerland (S.B.); University Hospital Basel, Basel, Switzerland (C.T., S.T.E.); Universitätsklinikum Erlangen, Erlangen, Germany (N.K., M.K.); Helsinki University Central Hospital, Helsinki, Finland (S.C., T.T.); Sahlgrenska University Hospital, Gothenburg, Sweden (T.T.); Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden (T.T.); and University Hospital Lausanne CHUV, Lausanne, Switzerland (P.M.). krassen.nedeltchev@ksa.ch.
authors.forename: Krassen
authors.initials: K
authors.lastname: Nedeltchev
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000188:drug therapy*; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D019233:Retreatment; D020521:Stroke / Q000188:drug therapy*; D015912:Thrombolytic Therapy / Q000009:adverse effects* / Q000379:methods; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator
keywords: hemorrhage; hospitalization; myocardial infarction; pulmonary embolism; stroke