Download PDF
Semin Neurol 2024; 44(03): 281-297
DOI: 10.1055/s-0044-1787046
Review Article

Updates in Management of Large Hemispheric Infarct

Charlene J. Ong
1   Department of Neurology, Chobanian and Avedisian School of Medicine, Boston University School of Medicine, Boston, Massachusetts
2   Department of Neurology, Boston Medical Center, 1 Boston Medical Center PI, Boston, Massachusetts
,
Stefanos Chatzidakis
3   Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
,
Jimmy J. Ong
4   Department of Neurology, Sidney Kimmel Medical College, Philadelphia, Pennsylvania
5   Department of Neurology, Jefferson Einstein Hospital, Philadelphia, Pennsylvania
,
Steven Feske
1   Department of Neurology, Chobanian and Avedisian School of Medicine, Boston University School of Medicine, Boston, Massachusetts
2   Department of Neurology, Boston Medical Center, 1 Boston Medical Center PI, Boston, Massachusetts
› Author Affiliations
› Further Information
    Permissions and Reprints

Abstract

This review delves into updates in management of large hemispheric infarction (LHI), a condition affecting up to 10% of patients with supratentorial strokes. While traditional management paradigms have endured, recent strides in research have revolutionized the approach to acute therapies, monitoring, and treatment. Notably, advancements in triage methodologies and the application of both pharmacological and mechanical abortive procedures have reshaped the acute care trajectory for patients with LHI. Moreover, ongoing endeavors have sought to refine strategies for the optimal surveillance and mitigation of complications, notably space-occupying mass effect, which can ensue in the aftermath of LHI. By amalgamating contemporary guidelines with cutting-edge clinical trial findings, this review offers a comprehensive exploration of the current landscape of acute and ongoing patient care for LHI, illuminating the evolving strategies that underpin effective management in this critical clinical domain.

Keywords

cerebral edema - ischemic stroke - space-occupying mass effect - thrombectomy


Publication History

Article published online:
17 May 2024

© 2024. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Huttner HB, Schwab S. Malignant middle cerebral artery infarction: clinical characteristics, treatment strategies, and future perspectives. Lancet Neurol 2009; 8 (10) 949-958
    CrossrefPubMedGoogle Scholar
  • 2 Powers WJ, Rabinstein AA, Ackerson T. et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2019; 50 (12) e344-e418
    CrossrefPubMedGoogle Scholar
  • 3 Thomalla G, Simonsen CZ, Boutitie F. et al; WAKE-UP Investigators. MRI-guided thrombolysis for stroke with unknown time of onset. N Engl J Med 2018; 379 (07) 611-622
    CrossrefPubMedGoogle Scholar
  • 4 National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995; 333 (24) 1581-1587
    CrossrefPubMedGoogle Scholar
  • 5 Hacke W, Kaste M, Bluhmki E. et al; ECASS Investigators. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 2008; 359 (13) 1317-1329
    CrossrefPubMedGoogle Scholar
  • 6 Ma H, Campbell BCV, Parsons MW. et al; EXTEND Investigators. Thrombolysis guided by perfusion imaging up to 9 hours after onset of stroke. N Engl J Med 2019; 380 (19) 1795-1803
    CrossrefPubMedGoogle Scholar
  • 7 Schwamm LH, Wu O, Song SS. et al; MR WITNESS Investigators. Intravenous thrombolysis in unwitnessed stroke onset: MR WITNESS trial results. Ann Neurol 2018; 83 (05) 980-993
    CrossrefPubMedGoogle Scholar
  • 8 Menon BK, Buck BH, Singh N. et al; AcT Trial Investigators. Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT): a pragmatic, multicentre, open-label, registry-linked, randomised, controlled, non-inferiority trial. Lancet 2022; 400 (10347): 161-169
    CrossrefPubMedGoogle Scholar
  • 9 Tong D, Reeves MJ, Hernandez AF. et al. Times from symptom onset to hospital arrival in the Get with the Guidelines–Stroke Program 2002 to 2009: temporal trends and implications. Stroke 2012; 43 (07) 1912-1917
    CrossrefPubMedGoogle Scholar
  • 10 Furlan A, Higashida R, Wechsler L. et al. Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in acute cerebral thromboembolism. JAMA 1999; 282 (21) 2003-2011
    CrossrefPubMedGoogle Scholar
  • 11 Broderick JP, Palesch YY, Demchuk AM. et al; Interventional Management of Stroke (IMS) III Investigators. Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med 2013; 368 (10) 893-903
    CrossrefPubMedGoogle Scholar
  • 12 Ciccone A, Valvassori L, Nichelatti M. et al; SYNTHESIS Expansion Investigators. Endovascular treatment for acute ischemic stroke. N Engl J Med 2013; 368 (10) 904-913
    CrossrefPubMedGoogle Scholar
  • 13 Kidwell CS, Jahan R, Gornbein J. et al; MR RESCUE Investigators. A trial of imaging selection and endovascular treatment for ischemic stroke. N Engl J Med 2013; 368 (10) 914-923
    CrossrefPubMedGoogle Scholar
  • 14 Berkhemer OA, Fransen PSS, Beumer D. et al; MR CLEAN Investigators. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med 2015; 372 (01) 11-20
    CrossrefPubMedGoogle Scholar
  • 15 Bracard S, Ducrocq X, Mas JL. et al; THRACE investigators. Mechanical thrombectomy after intravenous alteplase versus alteplase alone after stroke (THRACE): a randomised controlled trial. Lancet Neurol 2016; 15 (11) 1138-1147
    CrossrefPubMedGoogle Scholar
  • 16 Campbell BCV, Mitchell PJ, Kleinig TJ. et al; EXTEND-IA Investigators. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med 2015; 372 (11) 1009-1018
    CrossrefPubMedGoogle Scholar
  • 17 Goyal M, Demchuk AM, Menon BK. et al; ESCAPE Trial Investigators. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med 2015; 372 (11) 1019-1030
    CrossrefPubMedGoogle Scholar
  • 18 Goyal M, Menon BK, van Zwam WH. et al; HERMES collaborators. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet 2016; 387 (10029): 1723-1731
    CrossrefPubMedGoogle Scholar
  • 19 Jovin TG, Chamorro A, Cobo E. et al; REVASCAT Trial Investigators. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med 2015; 372 (24) 2296-2306
    CrossrefPubMedGoogle Scholar
  • 20 Muir KW, Ford GA, Messow CM. et al; PISTE Investigators. Endovascular therapy for acute ischaemic stroke: the Pragmatic Ischaemic Stroke Thrombectomy Evaluation (PISTE) randomised, controlled trial. J Neurol Neurosurg Psychiatry 2017; 88 (01) 38-44
    CrossrefPubMedGoogle Scholar
  • 21 Saver JL, Goyal M, Bonafe A. et al; SWIFT PRIME Investigators. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med 2015; 372 (24) 2285-2295
    CrossrefPubMedGoogle Scholar
  • 22 Albers GW, Marks MP, Kemp S. et al; DEFUSE 3 Investigators. Thrombectomy for stroke at 6 to 16 hours with selection by perfusion imaging. N Engl J Med 2018; 378 (08) 708-718
    CrossrefPubMedGoogle Scholar
  • 23 Nogueira RG, Jadhav AP, Haussen DC. et al; DAWN Trial Investigators. Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct. N Engl J Med 2018; 378 (01) 11-21
    CrossrefPubMedGoogle Scholar
  • 24 Bendszus M, Fiehler J, Subtil F. et al; TENSION Investigators. Endovascular thrombectomy for acute ischaemic stroke with established large infarct: multicentre, open-label, randomised trial. Lancet 2023; 402 (10414): 1753-1763
    CrossrefPubMedGoogle Scholar
  • 25 Huo X, Ma G, Tong X. et al; ANGEL-ASPECT Investigators. Trial of endovascular therapy for acute ischemic stroke with large infarct. N Engl J Med 2023; 388 (14) 1272-1283
    CrossrefPubMedGoogle Scholar
  • 26 Sarraj A, Hassan AE, Abraham MG. et al; SELECT2 Investigators. Trial of endovascular thrombectomy for large ischemic strokes. N Engl J Med 2023; 388 (14) 1259-1271
    CrossrefPubMedGoogle Scholar
  • 27 Yoshimura S, Sakai N, Yamagami H. et al. Endovascular therapy for acute stroke with a large ischemic region. N Engl J Med 2022; 386 (14) 1303-1313
    CrossrefPubMedGoogle Scholar
  • 28 Jovin TG, Li C, Wu L. et al; BAOCHE Investigators. Trial of thrombectomy 6 to 24 hours after stroke due to basilar-artery occlusion. N Engl J Med 2022; 387 (15) 1373-1384
    CrossrefPubMedGoogle Scholar
  • 29 Langezaal LCM, van der Hoeven EJRJ, Mont'Alverne FJA. et al; BASICS Study Group. Endovascular therapy for stroke due to basilar-artery occlusion. N Engl J Med 2021; 384 (20) 1910-1920
    CrossrefPubMedGoogle Scholar
  • 30 Liu X, Dai Q, Ye R. et al; BEST Trial Investigators. Endovascular treatment versus standard medical treatment for vertebrobasilar artery occlusion (BEST): an open-label, randomised controlled trial. Lancet Neurol 2020; 19 (02) 115-122
    CrossrefPubMedGoogle Scholar
  • 31 Tao C, Nogueira RG, Zhu Y. et al; ATTENTION Investigators. Trial of endovascular treatment of acute basilar-artery occlusion. N Engl J Med 2022; 387 (15) 1361-1372
    CrossrefPubMedGoogle Scholar
  • 32 Anderson CS, Arima H, Lavados P. et al; HeadPoST Investigators and Coordinators. Cluster-randomized, crossover trial of head positioning in acute stroke. N Engl J Med 2017; 376 (25) 2437-2447
    CrossrefPubMedGoogle Scholar
  • 33 van der Worp HB, Hofmeijer J, Jüttler E. et al. European Stroke Organisation (ESO) guidelines on the management of space-occupying brain infarction. Eur Stroke J 2021; 6 (02) XC-CX
    CrossrefPubMedGoogle Scholar
  • 34 Goostrey K, Muehlschlegel S. Prognostication and shared decision making in neurocritical care. BMJ 2022; 377: e060154
    CrossrefPubMedGoogle Scholar
  • 35 Waseem H, Keegan J, Farrell K. et al. Implementation of a standardized shared decision-making bundle to improve communication practices in the neurocritical care unit. Neurol Clin Pract 2023; 13 (01) e200120
    CrossrefPubMedGoogle Scholar
  • 36 Carson SS, Cox CE, Wallenstein S. et al. Effect of palliative care-led meetings for families of patients with chronic critical illness: a randomized clinical trial. JAMA 2016; 316 (01) 51-62
    CrossrefPubMedGoogle Scholar
  • 37 Shimoyama T, Kimura K, Uemura J. et al. The DASH score: a simple score to assess risk for development of malignant middle cerebral artery infarction. J Neurol Sci 2014; 338 (1-2): 102-106
    CrossrefPubMedGoogle Scholar
  • 38 Kasner SE, Demchuk AM, Berrouschot J. et al. Predictors of fatal brain edema in massive hemispheric ischemic stroke. Stroke 2001; 32 (09) 2117-2123
    CrossrefPubMedGoogle Scholar
  • 39 Jo K, Bajgur SS, Kim H, Choi HA, Huh PW, Lee K. A simple prediction score system for malignant brain edema progression in large hemispheric infarction. PLoS One 2017; 12 (02) e0171425
    CrossrefPubMedGoogle Scholar
  • 40 Cheng Y, Wu S, Wang Y. et al. External validation and modification of the EDEMA score for predicting malignant brain edema after acute ischemic stroke. Neurocrit Care 2020; 32 (01) 104-112
    CrossrefPubMedGoogle Scholar
  • 41 Ong CJ, Gluckstein J, Laurido-Soto O, Yan Y, Dhar R, Lee JM. Enhanced Detection of Edema in Malignant Anterior Circulation Stroke (EDEMA) score: a risk prediction tool. Stroke 2017; 48 (07) 1969-1972
    CrossrefPubMedGoogle Scholar
  • 42 Wu S, Wang Y, Yuan R. et al. Predicting the emergence of malignant brain oedema in acute ischaemic stroke: a prospective multicentre study with development and validation of predictive modelling. EClinicalMedicine 2023; 59: 101977
    CrossrefPubMedGoogle Scholar
  • 43 Wu S, Yuan R, Wang Y. et al. Early prediction of malignant brain edema after ischemic stroke. Stroke 2018; 49 (12) 2918-2927
    CrossrefPubMedGoogle Scholar
  • 44 Wijdicks EFM, Sheth KN, Carter BS. et al; American Heart Association Stroke Council. Recommendations for the management of cerebral and cerebellar infarction with swelling: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014; 45 (04) 1222-1238
    CrossrefPubMedGoogle Scholar
  • 45 Stafford R, Chatzidakis S, Kim ISY. et al. Follow-up ASPECTS improves prediction of potentially lethal malignant edema in patients with large middle cerebral artery stroke. J NeuroIntervent Surg 2023; jnis-2023-021145
    CrossrefPubMedGoogle Scholar
  • 46 Kim ISY, Balogun OO, Prescott BR. et al. Quantitative pupillometry and radiographic markers of intracranial midline shift: a pilot study. Front Neurol 2022; 13: 1046548
    CrossrefPubMedGoogle Scholar
  • 47 McKeown ME, Prasad A, Kobsa J. et al. Midline shift greater than 3 mm independently predicts outcome after ischemic stroke. Neurocrit Care 2022; 36 (01) 46-51
    CrossrefPubMedGoogle Scholar
  • 48 Ropper AH, Shafran B. Brain edema after stroke. Clinical syndrome and intracranial pressure. Arch Neurol 1984; 41 (01) 26-29
    CrossrefPubMedGoogle Scholar
  • 49 Broocks G, Flottmann F, Scheibel A. et al. Quantitative lesion water uptake in acute stroke computed tomography is a predictor of malignant infarction. Stroke 2018; 49 (08) 1906-1912
    CrossrefPubMedGoogle Scholar
  • 50 Dhar R, Chen Y, Hamzehloo A. et al. Reduction in cerebrospinal fluid volume as an early quantitative biomarker of cerebral edema after ischemic stroke. Stroke 2020; 51 (02) 462-467
    CrossrefPubMedGoogle Scholar
  • 51 Dhar R, Kumar A, Chen Y. et al. Imaging biomarkers of cerebral edema automatically extracted from routine CT scans of large vessel occlusion strokes. J Neuroimaging 2023; 33 (04) 606-616
    CrossrefPubMedGoogle Scholar
  • 52 Vorasayan P, Bevers MB, Beslow LA. et al. Intravenous glibenclamide reduces lesional water uptake in large hemispheric infarction. Stroke 2019; 50 (11) 3021-3027
    CrossrefPubMedGoogle Scholar
  • 53 Ong C, Huang Q, Kim I. et al. Dynamic trajectories of life-threatening mass effect in patients with large middle cerebral artery stroke. Version 1. Res Sq 2023; (e-pub ahead of print). DOI: 10.21203/rs.3.rs-3594179/v1.
    CrossrefPubMedGoogle Scholar
  • 54 Oddo M, Taccone FS, Petrosino M. et al; ORANGE study investigators. The Neurological Pupil index for outcome prognostication in people with acute brain injury (ORANGE): a prospective, observational, multicentre cohort study. Lancet Neurol 2023; 22 (10) 925-933
    CrossrefPubMedGoogle Scholar
  • 55 Ohle R, McIsaac SM, Woo MY, Perry JJ. Sonography of the optic nerve sheath diameter for detection of raised intracranial pressure compared to computed tomography: a systematic review and meta-analysis. J Ultrasound Med 2015; 34 (07) 1285-1294
    CrossrefPubMedGoogle Scholar
  • 56 Cardim D, Czosnyka M, Chandrapatham K. et al. Effects of age and sex on optic nerve sheath diameter in healthy volunteers and patients with traumatic brain injury. Front Neurol 2020; 11: 764
    CrossrefPubMedGoogle Scholar
  • 57 Moldes O, Sobrino T, Millán M. et al. High serum levels of endothelin-1 predict severe cerebral edema in patients with acute ischemic stroke treated with t-PA. Stroke 2008; 39 (07) 2006-2010
    CrossrefPubMedGoogle Scholar
  • 58 Rosell A, Ortega-Aznar A, Alvarez-Sabín J. et al. Increased brain expression of matrix metalloproteinase-9 after ischemic and hemorrhagic human stroke. Stroke 2006; 37 (06) 1399-1406
    CrossrefPubMedGoogle Scholar
  • 59 Bevers MB, Booraem C, Li K. et al. Association of soluble ST2 with functional outcome, perihematomal edema, and immune response after intraparenchymal hemorrhage. Neurology 2023; 100 (13) e1329-e1338
    CrossrefPubMedGoogle Scholar
  • 60 Cook AM, Morgan Jones G, Hawryluk GWJ. et al. Guidelines for the acute treatment of cerebral edema in neurocritical care patients. Neurocrit Care 2020; 32 (03) 647-666
    CrossrefPubMedGoogle Scholar
  • 61 Harutjunyan L, Holz C, Rieger A, Menzel M, Grond S, Soukup J. Efficiency of 7.2% hypertonic saline hydroxyethyl starch 200/0.5 versus mannitol 15% in the treatment of increased intracranial pressure in neurosurgical patients - a randomized clinical trial [ISRCTN62699180]. Crit Care 2005; 9 (05) R530-R540
    CrossrefPubMedGoogle Scholar
  • 62 Schwarz S, Schwab S, Bertram M, Aschoff A, Hacke W. Effects of hypertonic saline hydroxyethyl starch solution and mannitol in patients with increased intracranial pressure after stroke. Stroke 1998; 29 (08) 1550-1555
    CrossrefPubMedGoogle Scholar
  • 63 Schwarz S, Georgiadis D, Aschoff A, Schwab S. Effects of hypertonic (10%) saline in patients with raised intracranial pressure after stroke. Stroke 2002; 33 (01) 136-140
    CrossrefPubMedGoogle Scholar
  • 64 Hauer EM, Stark D, Staykov D, Steigleder T, Schwab S, Bardutzky J. Early continuous hypertonic saline infusion in patients with severe cerebrovascular disease. Crit Care Med 2011; 39 (07) 1766-1772
    CrossrefPubMedGoogle Scholar
  • 65 Qureshi AI, Suarez JI, Bhardwaj A. et al. Use of hypertonic (3%) saline/acetate infusion in the treatment of cerebral edema: effect on intracranial pressure and lateral displacement of the brain. Crit Care Med 1998; 26 (03) 440-446
    CrossrefPubMedGoogle Scholar
  • 66 Gondim Fde AA, Aiyagari V, Shackleford A, Diringer MN. Osmolality not predictive of mannitol-induced acute renal insufficiency. J Neurosurg 2005; 103 (03) 444-447
    CrossrefPubMedGoogle Scholar
  • 67 Lin SY, Tang SC, Tsai LK. et al. Incidence and risk factors for acute kidney injury following mannitol infusion in patients with acute stroke: a retrospective cohort study. Medicine (Baltimore) 2015; 94 (47) e2032
    CrossrefPubMedGoogle Scholar
  • 68 King ZA, Sheth KN, Kimberly WT, Simard JM. Profile of intravenous glyburide for the prevention of cerebral edema following large hemispheric infarction: evidence to date. Drug Des Devel Ther 2018; 12: 2539-2552
    CrossrefPubMedGoogle Scholar
  • 69 Sheth KN, Elm JJ, Molyneaux BJ. et al. Safety and efficacy of intravenous glyburide on brain swelling after large hemispheric infarction (GAMES-RP): a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol 2016; 15 (11) 1160-1169
    CrossrefPubMedGoogle Scholar
  • 70 Hofmeijer J, Kappelle LJ, Algra A, Amelink GJ, van Gijn J, van der Worp HB. HAMLET investigators. Surgical decompression for space-occupying cerebral infarction (the Hemicraniectomy After Middle Cerebral Artery infarction with Life-threatening Edema Trial [HAMLET]): a multicentre, open, randomised trial. Lancet Neurol 2009; 8 (04) 326-333
    CrossrefPubMedGoogle Scholar
  • 71 Jüttler E, Schwab S, Schmiedek P. et al; DESTINY Study Group. Decompressive surgery for the treatment of malignant infarction of the middle cerebral artery (DESTINY): a randomized, controlled trial. Stroke 2007; 38 (09) 2518-2525
    CrossrefPubMedGoogle Scholar
  • 72 Vahedi K, Vicaut E, Mateo J. et al; DECIMAL Investigators. Sequential-design, multicenter, randomized, controlled trial of early decompressive craniectomy in malignant middle cerebral artery infarction (DECIMAL Trial). Stroke 2007; 38 (09) 2506-2517
    CrossrefPubMedGoogle Scholar
  • 73 Hofmeijer J, van der Worp HB, Kappelle LJ, Amelink GJ, Algra A, van Zandvoort MJE. Cognitive outcome of survivors of space-occupying hemispheric infarction. J Neurol 2013; 260 (05) 1396-1403
    CrossrefPubMedGoogle Scholar
  • 74 Rahme R, Zuccarello M, Kleindorfer D, Adeoye OM, Ringer AJ. Decompressive hemicraniectomy for malignant middle cerebral artery territory infarction: is life worth living?. J Neurosurg 2012; 117 (04) 749-754
    CrossrefPubMedGoogle Scholar
  • 75 Reinink H, Jüttler E, Hacke W. et al. Surgical decompression for space-occupying hemispheric infarction: a systematic review and individual patient meta-analysis of randomized clinical trials. JAMA Neurol 2021; 78 (02) 208-216
    CrossrefPubMedGoogle Scholar
  • 76 Slezins J, Keris V, Bricis R. et al. Preliminary results of randomized controlled study on decompressive craniectomy in treatment of malignant middle cerebral artery stroke. Medicina (Kaunas) 2012; 48 (10) 521-524
    PubMedGoogle Scholar
  • 77 Zhao J, Su YY, Zhang Y. et al. Decompressive hemicraniectomy in malignant middle cerebral artery infarct: a randomized controlled trial enrolling patients up to 80 years old. Neurocrit Care 2012; 17 (02) 161-171
    CrossrefPubMedGoogle Scholar
  • 78 Fischer U, Koga M, Strbian D. et al; ELAN Investigators. Early versus later anticoagulation for stroke with atrial fibrillation. N Engl J Med 2023; 388 (26) 2411-2421
    CrossrefPubMedGoogle Scholar
  • 79 Oldgren J, Åsberg S, Hijazi Z, Wester P, Bertilsson M, Norrving B. National TIMING Collaborators. Early versus delayed non-vitamin k antagonist oral anticoagulant therapy after acute ischemic stroke in atrial fibrillation (TIMING): a registry-based randomized controlled noninferiority study. Circulation 2022; 146 (14) 1056-1066
    CrossrefPubMedGoogle Scholar
  • 80 Best JG, Arram L, Ahmed N. et al; OPTIMAS investigators. Optimal timing of anticoagulation after acute ischemic stroke with atrial fibrillation (OPTIMAS): protocol for a randomized controlled trial. Int J Stroke 2022; 17 (05) 583-589
    CrossrefPubMedGoogle Scholar
  • 81 Dennis M, Sandercock P, Graham C, Forbes J, Smith J. CLOTS (Clots in Legs Or sTockings after Stroke) Trials Collaboration. The clots in legs or stockings after stroke (CLOTS) 3 trial: a randomised controlled trial to determine whether or not intermittent pneumatic compression reduces the risk of post-stroke deep vein thrombosis and to estimate its cost-effectiveness. Health Technol Assess 2015; 19 (76) 1-90
    CrossrefPubMedGoogle Scholar
  • 82 Bösel J, Niesen WD, Salih F. et al; SETPOINT2 and the IGNITE Study Groups. Effect of early vs standard approach to tracheostomy on functional outcome at 6 months among patients with severe stroke receiving mechanical ventilation: the SETPOINT2 randomized clinical trial. JAMA 2022; 327 (19) 1899-1909
    CrossrefPubMedGoogle Scholar