PURPOSE: Beyond intravenous thrombolysis, evidence is lacking on acute treatment of minor stroke caused by large artery occlusion. To identify candidates for additional endovascular therapy, we aimed to determine the frequency of non-haemorrhagic early neurological deterioration in patients with intravenous thrombolysis-treated minor stroke caused by occlusion of large proximal and distal cerebral arteries. Secondary aims were to establish risk factors for non-haemorrhagic early neurological deterioration and report three-month outcomes in patients with and without non-haemorrhagic early neurological deterioration. METHOD: We analysed data from the SITS International Stroke Thrombolysis Register on 2553 patients with intravenous thrombolysis-treated minor stroke (NIH Stroke Scale scores 0-5) and available arterial occlusion data. Non-haemorrhagic early neurological deterioration was defined as an increase in NIH Stroke Scale score ≥4 at 24 h, without parenchymal hematoma on follow-up imaging within 22-36 h. FINDINGS: The highest frequency of non-haemorrhagic early neurological deterioration was seen in 30% of patients with terminal internal carotid artery or tandem occlusions (internal carotid artery + middle cerebral artery) (adjusted odds ratio: 10.3 (95% CI 4.3-24.9), p < 0.001) and 17% in extracranial carotid occlusions (adjusted odds ratio 4.3 (2.5-7.7), p < 0.001) versus 3.1% in those with no occlusion. Proximal middle cerebral artery-M1 occlusions had non-haemorrhagic early neurological deterioration in 9% (adjusted odds ratio 2.1 (0.97-4.4), p = 0.06). Among patients with any occlusion and non-haemorrhagic early neurological deterioration, 77% were dead or dependent at three months. CONCLUSIONS: Patients with minor stroke caused by internal carotid artery occlusion, with or without tandem middle cerebral artery involvement, are at high risk of disabling deterioration, despite intravenous thrombolysis treatment. Acute vessel imaging contributes usefully even in minor stroke to identify and consider endovascular treatment, or intensive monitoring at a comprehensive stroke centre, for patients at high risk of neurological deterioration.

Acute Stroke Service Oxford University Hospitals NHS Foundation Trust Oxford UK

Department of Clinical Neuroscience Karolinska Institutet Stockholm Sweden

Department of Neurology and Psychiatry University of Rome 'La Sapienza' Rome Italy

Department of Neurology Karolinska University Hospital Solna Sweden

Department of Neurology University Hospital and Faculty of Medicine University of Ostrava Ostrava Czech Republic

Department of Vascular Neurology and Neurological Intensive Care University Medical Center Ljubljana Ljubljana Slovenia

Institute of Cardiovascular and Medical Sciences University of Glasgow Glasgow UK

Luton and Dunstable NHSFT University Hospital Luton UK

Zobrazit více v PubMed

Emberson J, Lees KR, Lyden P, et al. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet 2014; 384: 1929–1935. PubMed PMC

Kharitonova T, Ahmed N, Thoren M, et al. Hyperdense middle cerebral artery sign on admission CT scan – prognostic significance for ischaemic stroke patients treated with intravenous thrombolysis in the safe implementation of thrombolysis in stroke international stroke thrombolysis register. Cerebrovasc Dis 2009; 27: 51–59. PubMed

Cooray C, Fekete K, Mikulik R, et al. Threshold for NIH stroke scale in predicting vessel occlusion and functional outcome after stroke thrombolysis. Int J Stroke 2015; 10: 822–829. PubMed

Heldner MR, Jung S, Zubler C, et al. Outcome of patients with occlusions of the internal carotid artery or the main stem of the middle cerebral artery with NIHSS score of less than 5: comparison between thrombolysed and non-thrombolysed patients. J Neurol Neurosurg Psychiatry 2015; 86: 755–760. PubMed

Kim JT, Park MS, Chang J, et al. Proximal arterial occlusion in acute ischemic stroke with low NIHSS scores should not be considered as mild stroke. PLoS One 2013; 8: e70996. PubMed PMC

Mori M, Naganuma M, Okada Y, et al. Early neurological deterioration within 24 h after intravenous rt-PA therapy for stroke patients: the stroke acute management with urgent risk factor assessment and improvement rt-PA registry. Cerebrovasc Dis 2012; 34: 140–146. PubMed

Rajajee V, Kidwell C, Starkman S, et al. Early MRI and outcomes of untreated patients with mild or improving ischemic stroke. Neurology 2006; 67: 980–984. PubMed

Dubuc V, Singh D, Modi J, et al. TIA and minor stroke patients with intracranial occlusions in both proximal and distal vessels are most at risk for symptom progression. Cerebrovasc Dis 2014; 38: 389–390. PubMed

Maas MB, Lev MH, Ay H, et al. Collateral vessels on CT angiography predict outcome in acute ischemic stroke. Stroke 2009; 40: 3001–3005. PubMed PMC

Tisserand M, Seners P, Turc G, et al. Mechanisms of unexplained neurological deterioration after intravenous thrombolysis. Stroke 2014; 45: 3527–3534. PubMed

Campbell BC, Christensen S, Tress BM, et al. Failure of collateral blood flow is associated with infarct growth in ischemic stroke. J Cereb Blood Flow Metab 2013; 33: 1168–1172. PubMed PMC

Campbell BC, Donnan GA, Davis SM. Vessel occlusion, penumbra, and reperfusion – translating theory to practice. Front Neurol 2014; 5: 194. PubMed PMC

Seners P, Hurford R, Tisserand M, et al. Is unexplained early neurological deterioration after intravenous thrombolysis associated with thrombus extension? Stroke 2017; 48: 348–352. PubMed

Khatri P, Conaway MR, Johnston KC. Ninety-day outcome rates of a prospective cohort of consecutive patients with mild ischemic stroke. Stroke 2012; 43: 560–562. PubMed PMC

Seners P, Turc G, Oppenheim C, et al. Incidence, causes and predictors of neurological deterioration occurring within 24 h following acute ischaemic stroke: a systematic review with pathophysiological implications. J Neurol Neurosurg Psychiatry 2015; 86: 87–94. PubMed

Coutts SB, Modi J, Patel SK, et al. What causes disability after transient ischemic attack and minor stroke?: results from the CT and MRI in the Triage of TIA and minor Cerebrovascular Events to Identify High Risk Patients (CATCH) Study. Stroke 2012; 43: 3018–3022. PubMed

Coutts SB, Modi J, Patel SK, et al. CT/CT angiography and MRI findings predict recurrent stroke after transient ischemic attack and minor stroke: results of the prospective CATCH study. Stroke 2012; 43: 1013–1017. PubMed

Rodrigues FB, Neves JB, Caldeira D, et al. Endovascular treatment versus medical care alone for ischaemic stroke: systematic review and meta-analysis. BMJ 2016; 353: i1754. PubMed PMC

Powers WJ, Derdeyn CP, Biller J, et al. 2015 American heart association/American stroke association focused update of the 2013 guidelines for the early management of patients with acute ischemic stroke regarding endovascular treatment: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2015; 46: 3020–3035. PubMed

Ahmed N, Wahlgren N, Grond M, et al. Implementation and outcome of thrombolysis with alteplase 3–4.5 h after an acute stroke: an updated analysis from SITS-ISTR. Lancet Neurol 2010; 9: 866–874. PubMed

Wahlgren N, Ahmed N, Davalos A, et al. Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study. Lancet 2007; 369: 275–282. PubMed

Mazya MV, Ahmed N, Ford GA, et al. Remote or extraischemic intracerebral hemorrhage – an uncommon complication of stroke thrombolysis: results from the safe implementation of treatments in stroke-international stroke thrombolysis register. Stroke 2014; 45: 1657–1663. PubMed

Mazya MV, Lees KR, Collas D, et al. IV thrombolysis in very severe and severe ischemic stroke: results from the SITS-ISTR registry. Neurology 2015; 85: 2098–2106. PubMed PMC

Romano JG, Smith EE, Liang L, et al. Outcomes in mild acute ischemic stroke treated with intravenous thrombolysis: a retrospective analysis of the get with the guidelines-stroke registry. JAMA Neurol 2015; 72: 423–431. PubMed

Kohrmann M, Nowe T, Huttner HB, et al. Safety and outcome after thrombolysis in stroke patients with mild symptoms. Cerebrovasc Dis 2009; 27: 160–166. PubMed

Zhu W, Churilov L, Campbell BC, et al. Does large vessel occlusion affect clinical outcome in stroke with mild neurologic deficits after intravenous thrombolysis? J Stroke Cerebrovasc Dis 2014; 23: 2888–2893. PubMed

Laurencin C, Philippeau F, Blanc-Lasserre K, et al. Thrombolysis for acute minor stroke: outcome and barriers to management. Results from the RESUVAL stroke network. PubMed

Choi JC, Jang MU, Kang K, et al. Comparative effectiveness of standard care with IV thrombolysis versus without IV thrombolysis for mild ischemic stroke. J Am Heart Assoc 2015; 4: e001306. PubMed PMC

Ahn SH, d’Esterre CD, Qazi EM, et al. Occult anterograde flow is an under-recognized but crucial predictor of early recanalization with intravenous tissue-type plasminogen activator. Stroke 2015; 46: 968–975. PubMed

Seners P, Hurford R, Tisserand M, et al. Is unexplained early neurological deterioration after intravenous thrombolysis associated with thrombus extension? Stroke 2017; 48: 348. PubMed

Seners P, Turc G, Tisserand M, et al. Unexplained early neurological deterioration after intravenous thrombolysis: incidence, predictors, and associated factors. Stroke 2014; 45: 2004–2009. PubMed

Alawneh JA, Moustafa RR, Baron JC. Hemodynamic factors and perfusion abnormalities in early neurological deterioration. Stroke 2009; 40: e443–e450. PubMed

Alawneh JA, Jones PS, Mikkelsen IK, et al. Infarction of ‘non-core-non-penumbral’ tissue after stroke: multivariate modelling of clinical impact. Brain 2011; 134: 1765–1776. PubMed

Sheth SA, Sanossian N, Hao Q, et al. Collateral flow as causative of good outcomes in endovascular stroke therapy. J Neurointerv Surg 2016; 8: 2–7. PubMed PMC

Simonsen CZ, Schmitz ML, Madsen MH, et al. Early neurological deterioration after thrombolysis: clinical and imaging predictors. PubMed

Zinkstok SM, Roos YB. ARTIS-Investigators. Early administration of aspirin in patients treated with alteplase for acute ischaemic stroke: a randomised controlled trial. Lancet 2012; 380: 731–737. PubMed

Wahlgren N, Moreira T, Michel P, et al. Mechanical thrombectomy in acute ischemic stroke: consensus statement by ESO-Karolinska Stroke Update 2014/2015, supported by ESO, ESMINT, ESNR and EAN. Int J Stroke 2016; 11: 134–147. PubMed

Haussen DC, Bouslama M, Grossberg JA, et al. Too good to intervene? Thrombectomy for large vessel occlusion strokes with minimal symptoms: an intention-to-treat analysis. J Neurointerv Surg 2017; 9: 917–921. PubMed

Haussen DC, Lima FO, Bouslama M, et al. Thrombectomy versus medical management for large vessel occlusion strokes with minimal symptoms: an analysis from STOPStroke and GESTOR cohorts. PubMed

Messer MP, Schonenberger S, Mohlenbruch MA, et al. Minor stroke syndromes in large-vessel occlusions: mechanical thrombectomy or thrombolysis only? Am J Neuroradiol 2017; 38: 1177–1179. PubMed PMC