title: Mechanisms of unexplained neurological deterioration after intravenous thrombolysis.
abstract: OBJECTIVE
  Unstable clinical course characterizes the first 24 hours after thrombolysis for anterior circulation stroke, including early neurological deterioration (END), a secondary complication consistently predictive of poor outcome. Apart from straightforward causes, such as intracerebral hemorrhage and malignant edema, the mechanism of END remains unclear in the majority of cases (ENDunexplained). Based on the core/penumbra model, we tested the hypothesis that ENDunexplained is caused by infarct growth beyond the initial penumbra and assessed the associated vascular patterns.
  
  
  METHODS
  From our database of consecutive thrombolyzed patients (n=309), we identified 10 ENDunexplained cases who had undergone both admission and 24-hour MRI. Diffusion-weighted imaging lesion growth both within and beyond the acute penumbra (Tmax>6 seconds) was mapped voxelwise. These 10 cases were compared with 30 no-END controls extracted from the database blinded to 24-hour diffusion-weighted imaging to individually match cases (3/case) according to 4 previously identified clinical and imaging variables.
  
  
  RESULTS
  As predicted, lesion growth beyond initial penumbra was present in 9 of 10 ENDunexplained patients (substantial in 8) and its volume was significantly larger in cases than controls (2P=0.047). All ENDunexplained cases had proximal arterial occlusion initially, of which only 2 had recanalized at 24 hours.
  
  
  CONCLUSIONS
  In this exploratory study, most instances of ENDunexplained were related to diffusion-weighted imaging growth beyond acute penumbra. Consistent presence of proximal occlusion at admission and lack of recanalization at 24 hours in most cases suggest that hemodynamic factors played a key role, via for instance systemic instability/collateral failure or secondary thromboembolic processes. Preventing END after tissue-type plasminogen activator using, eg, early antithrombotics may therefore be feasible.
authors.affiliation: From the INSERM UMR S894, Sorbonne Paris Cité, Service de Neuroradiologie (M.T., L.L., M.-A.L., S.C., J.-F.M., C.O.) and INSERM UMR S894, Sorbonne Paris Cité, Service de Neurologie (P.S., G.T., J.-L.M., J.-C.B.), Centre Hospitalier Sainte-Anne, Paris, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Tisserand
authors.affiliation: From the INSERM UMR S894, Sorbonne Paris Cité, Service de Neuroradiologie (M.T., L.L., M.-A.L., S.C., J.-F.M., C.O.) and INSERM UMR S894, Sorbonne Paris Cité, Service de Neurologie (P.S., G.T., J.-L.M., J.-C.B.), Centre Hospitalier Sainte-Anne, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Seners
authors.affiliation: From the INSERM UMR S894, Sorbonne Paris Cité, Service de Neuroradiologie (M.T., L.L., M.-A.L., S.C., J.-F.M., C.O.) and INSERM UMR S894, Sorbonne Paris Cité, Service de Neurologie (P.S., G.T., J.-L.M., J.-C.B.), Centre Hospitalier Sainte-Anne, Paris, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Turc
authors.affiliation: From the INSERM UMR S894, Sorbonne Paris Cité, Service de Neuroradiologie (M.T., L.L., M.-A.L., S.C., J.-F.M., C.O.) and INSERM UMR S894, Sorbonne Paris Cité, Service de Neurologie (P.S., G.T., J.-L.M., J.-C.B.), Centre Hospitalier Sainte-Anne, Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Legrand
authors.affiliation: From the INSERM UMR S894, Sorbonne Paris Cité, Service de Neuroradiologie (M.T., L.L., M.-A.L., S.C., J.-F.M., C.O.) and INSERM UMR S894, Sorbonne Paris Cité, Service de Neurologie (P.S., G.T., J.-L.M., J.-C.B.), Centre Hospitalier Sainte-Anne, Paris, France.
authors.forename: Marc-Antoine
authors.initials: MA
authors.lastname: Labeyrie
authors.affiliation: From the INSERM UMR S894, Sorbonne Paris Cité, Service de Neuroradiologie (M.T., L.L., M.-A.L., S.C., J.-F.M., C.O.) and INSERM UMR S894, Sorbonne Paris Cité, Service de Neurologie (P.S., G.T., J.-L.M., J.-C.B.), Centre Hospitalier Sainte-Anne, Paris, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Charron
authors.affiliation: From the INSERM UMR S894, Sorbonne Paris Cité, Service de Neuroradiologie (M.T., L.L., M.-A.L., S.C., J.-F.M., C.O.) and INSERM UMR S894, Sorbonne Paris Cité, Service de Neurologie (P.S., G.T., J.-L.M., J.-C.B.), Centre Hospitalier Sainte-Anne, Paris, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Méder
authors.affiliation: From the INSERM UMR S894, Sorbonne Paris Cité, Service de Neuroradiologie (M.T., L.L., M.-A.L., S.C., J.-F.M., C.O.) and INSERM UMR S894, Sorbonne Paris Cité, Service de Neurologie (P.S., G.T., J.-L.M., J.-C.B.), Centre Hospitalier Sainte-Anne, Paris, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mas
authors.affiliation: From the INSERM UMR S894, Sorbonne Paris Cité, Service de Neuroradiologie (M.T., L.L., M.-A.L., S.C., J.-F.M., C.O.) and INSERM UMR S894, Sorbonne Paris Cité, Service de Neurologie (P.S., G.T., J.-L.M., J.-C.B.), Centre Hospitalier Sainte-Anne, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Oppenheim
authors.affiliation: From the INSERM UMR S894, Sorbonne Paris Cité, Service de Neuroradiologie (M.T., L.L., M.-A.L., S.C., J.-F.M., C.O.) and INSERM UMR S894, Sorbonne Paris Cité, Service de Neurologie (P.S., G.T., J.-L.M., J.-C.B.), Centre Hospitalier Sainte-Anne, Paris, France. jean-claude.baron@inserm.fr.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Baron
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008297:Male; D008875:Middle Aged; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology*; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator
keywords: magnetic resonance imaging; physiopathology; stroke; thrombolysis