Time to recanalization and risk of symptomatic intracerebral haemorrhage in patients treated with intravenous thrombolysis L. Dorado a , M. Milla ´n a , N. Pe ´rez de la Ossa a , C. Guerrero a , M. Gomis a , A. Aleu a , E. Lo ´ pez-Cancio a , P. Cuadras b and A. Da ´ valos a a Stroke Unit, Department of Neurosciences, Hospital Universitari Germans Trias i Pujol, Universitat Auto `noma de Barcelona, Badalona (Barcelona), Spain; and b Department of Radiology, Hospital Universitari Germans Trias i Pujol, Universitat Auto `noma de Barcelona, Badalona (Barcelona), Spain Keywords: acute ischaemic stroke, recanalization, symptomatic intracranial haemorrhage, thrombolytic therapy Received 9 November 2011 Accepted 13 March 2012 Background and purpose: To test whether time to recanalization is associated with a progressive risk of symptomatic intracerebral haemorrhage (SICH) after intrave- nous alteplase (IVT), we conducted a serial transcranial duplex monitoring study up to 24 h after IVT in a cohort of 140 patients with acute ischaemic stroke attributed to large artery occlusion in the anterior circulation. Methods: Patients were classified in four groups according to the time to complete recanalization (Thrombolysis in Brain Ischaemia, TIBI grades 4 or 5) after alteplase bolus: <2h(n = 53), 2–6h(n = 9), 6–24 h (n = 32) and no recanalization (NR) at 24 h (n = 46). SICH was defined as any haemorrhagic transformation with National Institute of Health Stroke Scale (NIHSS) score worsening 4 points (European Australian Acute Stroke Study II, ECASS II criteria) or parenchymal haematoma type 2 with neurological worsening (SITS-MOST criteria) in the 24–36 h CT. Favourable outcome was defined as modified Rankin score 2 at 3 months. Results: There were no differences between the groups of patients who recanalized at each time frame regarding localization of the occlusion (P = 0.29), stroke severity at baseline (P = 0.22) and age (P = 0.06). SICH (ECASS/SITS-MOST) was observed in 5.7%/5.7% of the patients who recanalized in <2 h, in 0%/0% of the patients who recanalized between 2–6 h, in 3.1%/3.1% of the patients who recanal- ized within 6–24 h and in 2.2%/0% of those patients who did not recanalize at 24 h. The rate of favourable outcome according to the time of recanalization was 79.2%, 50%, 46.9% and 34.1% (P < 0.001). Conclusions: Our findings are in line with the literature showing a relationship between time to recanalization and functional outcome after IVT in acute stroke, but they do not confirm a progressive increase in the rate of SICH. Introduction Thrombolytic therapy with intravenous tissue plas- minogen activator (IVT) is the only medical treatment that has proven to be effective in routine clinical use for acute ischaemic stroke when given within 4.5 h from the onset of symptoms [1–3]. However, its use is associated with an increased risk of intracerebral haemorrhage (ICH) [4]. In a pooled analysis of eight randomized placebo-controlled trials of IVT for stroke, there was a non-significant trend of a positive interaction between time to treatment and risk of rele- vant parenchymal haemorrhage (PH) [5]. Moreover, in the Safe Implementation of Treatment in Stroke-International Stroke Thrombolysis Registry (SITS-ISTR) and Canadian Alteplase for Stroke Effectiveness Study (CASES) registry, the rate of symptomatic intracerebral haemorrhage (SICH) was higher in patients treated in the 3–4.5-h window than in patients treated within 3 h [6,7]. Studies in rodent models of middle cerebral artery (MCA) occlusion have shown that time to artery reopening is an important risk factor for ICH [8–10]. Regarding clinical studies, delayed recanalization (>6 h) [11] and persistent occlusion beyond 2 h after Correspondence: L. Dorado, Stroke Unit, Department of Neuro- sciences, Hospital Universitari Germans Trias i Pujol, Universitat Auto`noma de Barcelona, Carretera de Canyet s/n, 08916 Badalona (Barcelona), Spain (tel.: +34 93 497 8911; fax: +34 93 497 87 42; e-mail: 36458ldb@comb.cat, lauritadb@yahoo.es). © 2012 The Author(s) European Journal of Neurology © 2012 EFNS 1 European Journal of Neurology 2012 doi:10.1111/j.1468-1331.2012.03743.x