Jose G Romano1, Shyam Prabhakaran2, Azhar Nizam3, Edward Feldmann4, Rajbeer Sangha5, George Cotsonis6, Iszet Campo-Bustillo7, Sebastian Koch8, Tatjana Rundek9, Marc I Chimowitz10, David S Liebeskind11. 1. University of Miami, 1120 NW 14th Street, Suite 1357, Miami, FL 33136, USA. Electronic address: jromano@med.miami.edu. 2. The University of Chicago, Chicago, IL, USA. Electronic address: shyam1@neurology.bsd.uchicago.edu. 3. Emory University, Atlanta, GA, USA. Electronic address: anizam@emory.edu. 4. The University of Massachusetts Medical School-Baystate, Springfield, MA, USA. Electronic address: Edward.Feldmann@baystatehealth.org. 5. University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: rssangha@uabmc.edu. 6. Emory University, Atlanta, GA, USA. Electronic address: gcotson@emory.edu. 7. Iszet Campo-Bustillo, MD, MPH. University of Miami, Miami, FL, USA. Electronic address: icampo@miami.edu. 8. University of Miami, Miami, FL, USA. Electronic address: skoch@med.miami.edu. 9. University of Miami, Miami, FL, USA. Electronic address: trundek@med.miami.edu. 10. Medical University of South Carolina, Charleston, SC, USA. Electronic address: mchimow@musc.edu. 11. University of California at Los Angeles, Los Angeles, CA, USA. Electronic address: dliebeskind@mednet.ucla.edu.
Abstract
BACKGROUND: Intracranial atherosclerotic disease (ICAD) is a common cause of ischemic stroke with a high risk of clinical stroke recurrence. Multiple mechanisms may underlie cerebral ischemia in this condition. The study's objective is to discern the mechanisms of recurrent ischemia in ICAD through imaging biomarkers of impaired antegrade flow, poor distal perfusion, abnormal vasoreactivity, and artery-to-artery embolism. METHODS: This prospective multicenter observational study enrolled patients with recent (≤21 days) ischemic stroke or transient ischemic attack (TIA) caused by ICAD with 50-99% stenosis treated medically. We obtained baseline quantitative MRA (QMRA), perfusion MRI (PWI), transcranial Doppler vasoreactivity (VMR), and emboli detection studies (EDS). The primary outcome was ischemic stroke in the territory of the stenotic artery within 1 year of follow-up; secondary outcomes were TIA at 1 year and new infarcts in the territory on MRI at 6-8 weeks. RESULTS: Amongst 102 of 105 participants with clinical follow-up (mean 253±131 days), the primary outcome occurred in 8.8% (12.7/100 patient-years), while 5.9% (8.5/100 patient-years) had a TIA. A new infarct in the territory of the symptomatic artery was noted in 24.7% at 6-8 weeks. A low flow state on QMRA was noted in 25.5%, poor distal perfusion on PWI in 43.5%, impaired vasoreactivity on VMR in 67.5%, and microemboli on EDS in 39.0%. No significant association was identified between these imaging biomarkers and primary or secondary outcomes. CONCLUSIONS: Despite intensive medical management in ICAD, there is a high risk of clinical cerebrovascular events at 1 year and an even higher risk of new imaging-evident infarcts in the subacute period after index stroke. Hemodynamic and plaque instability biomarkers did not identify a higher risk group. Further work is needed to identify mechanisms of ischemic stroke and infarct recurrence and their consequence on long-term physical and cognitive outcomes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02121028.
BACKGROUND: Intracranial atherosclerotic disease (ICAD) is a common cause of ischemic stroke with a high risk of clinical stroke recurrence. Multiple mechanisms may underlie cerebral ischemia in this condition. The study's objective is to discern the mechanisms of recurrent ischemia in ICAD through imaging biomarkers of impaired antegrade flow, poor distal perfusion, abnormal vasoreactivity, and artery-to-artery embolism. METHODS: This prospective multicenter observational study enrolled patients with recent (≤21 days) ischemic stroke or transient ischemic attack (TIA) caused by ICAD with 50-99% stenosis treated medically. We obtained baseline quantitative MRA (QMRA), perfusion MRI (PWI), transcranial Doppler vasoreactivity (VMR), and emboli detection studies (EDS). The primary outcome was ischemic stroke in the territory of the stenotic artery within 1 year of follow-up; secondary outcomes were TIA at 1 year and new infarcts in the territory on MRI at 6-8 weeks. RESULTS: Amongst 102 of 105 participants with clinical follow-up (mean 253±131 days), the primary outcome occurred in 8.8% (12.7/100 patient-years), while 5.9% (8.5/100 patient-years) had a TIA. A new infarct in the territory of the symptomatic artery was noted in 24.7% at 6-8 weeks. A low flow state on QMRA was noted in 25.5%, poor distal perfusion on PWI in 43.5%, impaired vasoreactivity on VMR in 67.5%, and microemboli on EDS in 39.0%. No significant association was identified between these imaging biomarkers and primary or secondary outcomes. CONCLUSIONS: Despite intensive medical management in ICAD, there is a high risk of clinical cerebrovascular events at 1 year and an even higher risk of new imaging-evident infarcts in the subacute period after index stroke. Hemodynamic and plaque instability biomarkers did not identify a higher risk group. Further work is needed to identify mechanisms of ischemic stroke and infarct recurrence and their consequence on long-term physical and cognitive outcomes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02121028.
Authors: Sepideh Amin-Hanjani; Dilip K Pandey; Linda Rose-Finnell; Xinjian Du; DeJuran Richardson; Keith R Thulborn; Mitchell S V Elkind; Gregory J Zipfel; David S Liebeskind; Frank L Silver; Scott E Kasner; Victor A Aletich; Louis R Caplan; Colin P Derdeyn; Philip B Gorelick; Fady T Charbel Journal: JAMA Neurol Date: 2016-02 Impact factor: 18.302
Authors: Tanya N Turan; Michael J Lynn; Azhar Nizam; Bethany Lane; Brent M Egan; Ngoc-Anh Le; Maria F Lopes-Virella; Kathie L Hermayer; Oscar Benavente; Carole L White; W Virgil Brown; Michelle F Caskey; Meghan R Steiner; Nicole Vilardo; Andrew Stufflebean; Colin P Derdeyn; David Fiorella; Scott Janis; Marc I Chimowitz Journal: Circ Cardiovasc Qual Outcomes Date: 2012-09-01
Authors: Colin P Derdeyn; Marc I Chimowitz; Michael J Lynn; David Fiorella; Tanya N Turan; L Scott Janis; Jean Montgomery; Azhar Nizam; Bethany F Lane; Helmi L Lutsep; Stanley L Barnwell; Michael F Waters; Brian L Hoh; J Maurice Hourihane; Elad I Levy; Andrei V Alexandrov; Mark R Harrigan; David Chiu; Richard P Klucznik; Joni M Clark; Cameron G McDougall; Mark D Johnson; G Lee Pride; John R Lynch; Osama O Zaidat; Zoran Rumboldt; Harry J Cloft Journal: Lancet Date: 2013-10-26 Impact factor: 79.321
Authors: Rebecca F Gottesman; Thomas H Mosley; David S Knopman; Qing Hao; Dean Wong; Lynne E Wagenknecht; Timothy M Hughes; Ye Qiao; Jennifer Dearborn; Bruce A Wasserman Journal: JAMA Neurol Date: 2020-03-01 Impact factor: 18.302
Authors: Shyam Prabhakaran; David S Liebeskind; George Cotsonis; Azhar Nizam; Edward Feldmann; Rajbeer S Sangha; Iszet Campo-Bustillo; Jose G Romano Journal: J Stroke Cerebrovasc Dis Date: 2021-10-26 Impact factor: 2.136
Authors: Brian Mac Grory; Shadi Yaghi; Charlotte Cordonnier; Luciano A Sposato; Jose G Romano; Seemant Chaturvedi Journal: Circ Res Date: 2022-04-14 Impact factor: 23.213
Authors: Shyam Prabhakaran; David S Liebeskind; George Cotsonis; Azhar Nizam; Edward Feldmann; Rajbeer S Sangha; Iszet Campo-Bustillo; Jose G Romano Journal: Stroke Date: 2021-04-19 Impact factor: 10.170
Authors: Ahmad A Ballout; Richard B Libman; Julia R Schneider; Karen Black; Panagiotis Sideras; Jason J Wang; Timothy G White; Amir R Dehdashti; Henry H Woo; Jeffrey M Katz Journal: J Am Heart Assoc Date: 2022-02-16 Impact factor: 6.106
Authors: Victor J Del Brutto; David S Liebeskind; Jose G Romano; Iszet Campo-Bustillo; George Cotsonis; Azhar Nizam; Shyam Prabhakaran Journal: J Stroke Cerebrovasc Dis Date: 2021-06-30 Impact factor: 2.677