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Recanalisation artérielle précoce après thrombolyse intraveineuse d’un accident ischémique cérébral avec occlusion artérielle proximale : incidence, prédiction et physiopathologie

Abstract : In acute stroke patients with large-vessel occlusion (LVO), the goal of intravenous thrombolysis (IVT) is to achieve early recanalization. Whether all patients with LVO need to undergo intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) – i.e. bridging therapy, which is standard-of-care since 2015 – is debated as: i) thrombolysis may be harmful in patients unlikely to recanalize following IVT; and, ii) conversely, transfer for MT may be unnecessary in patients highly likely to recanalize. It is therefore timely and important to investigate the mechanisms and predictors of post-IVT recanalization, since the findings could have major clinical implications, such as the development of more efficient intravenous therapies, as well as moving towards personalized medicine, involving the selection of individual patients for best therapy, i.e., IVT alone, bridging, or MT alone. In the present thesis, we studied the incidence and predictors of post-IVT early recanalization in a large French multicentric cohort of acute stroke with LVO (n=1107), where all patients were treated with IVT and referred for MT between 2015 and 2017. Recanalization was evaluated on first intracranial angiogram or non-invasive vascular imaging within the first 3h following IVT start. The incidence of early recanalization following IVT was substantial in the overall cohort, occurring in ~1 in 5 patients. Thrombus site and length, time elapsed between IVT start and recanalization assessment, and quality of the leptomeningeal collateral flow or severity of hypoperfusion, were all independently associated with early recanalization occurrence. These findings are novel and important, and shed new light on the mechanisms underlying post-IVT recanalization. A six-point score derived from the three former variables afforded >90% specificity for no-recanalization, but did not reliably predict occurrence of early recanalization. This score should prove of value for patient selection into trials, testing e.g. bridging therapy vs. MT alone, but may not be used to support decisions to withhold referral for MT. In the subgroup of LVO patients with minor neurological symptoms (NIHSS score <6), in whom the optimal treatment is unknown, we found that thrombus length was a powerful independent predictor of no-recanalization, and that the optimal cutoff (9mm) had a high sensitivity/specificity ratio for no-recanalization, which may help design randomized trials aiming to test bridging therapy vs. IVT alone in this population. Lastly, unlike the EXTEND-IA TNK randomized trial which found 2-fold higher early recanalization rate before mechanical MT following IVT with tenecteplase as compared to alteplase in patients directly admitted to MT-capable centres, we found similar early recanalization rates with these two thrombolytic agents in patients transferred for MT from a non MT-capable centre (i.e., with longer IVT-to-MT delays than in EXTEND-IA TNK), currently the most frequently encountered clinical situation. Taken together, these data suggest that recanalization may occur earlier with tenecteplase, which if confirmed would have clinical relevance. Towards further clarifying the pathophysiology of post-thrombolysis early recanalization failure and develop more efficient intravenous therapies for acute ischemic stroke, specific studies will need to address two additional potentially important predictors of early recanalization, namely haemostatic biomarkers and thrombus composition.
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Pierre Seners. Recanalisation artérielle précoce après thrombolyse intraveineuse d’un accident ischémique cérébral avec occlusion artérielle proximale : incidence, prédiction et physiopathologie. Neurosciences [q-bio.NC]. Université Sorbonne Paris Cité, 2018. Français. ⟨NNT : 2018USPCB222⟩. ⟨tel-02466626⟩

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