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March 07, 2023; 100 (10) Research Article

Neurologic Improvement in Acute Cerebral Ischemia

Frequency, Magnitude, Predictors, and Clinical Outcomes

View ORCID ProfileClotilde Balucani, Steven R. Levine, Nerses Sanossian, Sidney Starkman, David Liebeskind, Jeffrey A. Gornbein, Kristina Shkirkova, Samuel Stratton, Marc Eckstein, Scott Hamilton, Robin Conwit, Latisha K. Sharma, Jeffrey L. Saver
First published December 7, 2022, DOI: https://doi.org/10.1212/WNL.0000000000201656
Clotilde Balucani
From the Department of Neurology (C.B.), Neurocritical Care Division, NYU Langone Medical Center, Bellevue Hospital, New York, NY; Department of Neurology (S.R.L.), The State University of New York Downstate Medical Center, Brooklyn, NY & the Jaffe Stroke Center, Maimonides Medical Center, Brooklyn, NY; Department of Neurology and Emergency Medicine (S.R.L.), Kings County Hospital Center, Brooklyn, NY; Department of Neurology (N.S.), University of Southern California, Los Angeles, CA; Department of Emergency Medicine (Sidney Starkman), University of California, Los Angeles, CA; Stroke Center (Sidney Starkman, D.L., K.S., L.K.S., J.L.S.), Department of Neurology, University of California, Los Angeles, CA; Department of Biomathematics (J.A.G.), David Geffen School of Medicine at UCLA, Los Angeles, CA; Department of Emergency Medicine (Samuel Stratton), Harbor-University of California, Los Angeles Medical Center, LA; Los Angeles EMS Agency (Samuel Stratton), Los Angeles, CA; Orange County EMS Agency (Samuel Stratton), Orange County, CA; Department of Emergency Medicine (M.E.), University of Southern California, Los Angeles, CA; Los Angeles Fire Department (M.E.), Los Angeles, CA; Department of Neurology (S.H.), Stanford University, Stanford, CA; and National Institute of Neurological Disorders and Stroke (R.C.), National Institutes of Health, Bethesda, MD.
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  • ORCID record for Clotilde Balucani
Steven R. Levine
From the Department of Neurology (C.B.), Neurocritical Care Division, NYU Langone Medical Center, Bellevue Hospital, New York, NY; Department of Neurology (S.R.L.), The State University of New York Downstate Medical Center, Brooklyn, NY & the Jaffe Stroke Center, Maimonides Medical Center, Brooklyn, NY; Department of Neurology and Emergency Medicine (S.R.L.), Kings County Hospital Center, Brooklyn, NY; Department of Neurology (N.S.), University of Southern California, Los Angeles, CA; Department of Emergency Medicine (Sidney Starkman), University of California, Los Angeles, CA; Stroke Center (Sidney Starkman, D.L., K.S., L.K.S., J.L.S.), Department of Neurology, University of California, Los Angeles, CA; Department of Biomathematics (J.A.G.), David Geffen School of Medicine at UCLA, Los Angeles, CA; Department of Emergency Medicine (Samuel Stratton), Harbor-University of California, Los Angeles Medical Center, LA; Los Angeles EMS Agency (Samuel Stratton), Los Angeles, CA; Orange County EMS Agency (Samuel Stratton), Orange County, CA; Department of Emergency Medicine (M.E.), University of Southern California, Los Angeles, CA; Los Angeles Fire Department (M.E.), Los Angeles, CA; Department of Neurology (S.H.), Stanford University, Stanford, CA; and National Institute of Neurological Disorders and Stroke (R.C.), National Institutes of Health, Bethesda, MD.
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Nerses Sanossian
From the Department of Neurology (C.B.), Neurocritical Care Division, NYU Langone Medical Center, Bellevue Hospital, New York, NY; Department of Neurology (S.R.L.), The State University of New York Downstate Medical Center, Brooklyn, NY & the Jaffe Stroke Center, Maimonides Medical Center, Brooklyn, NY; Department of Neurology and Emergency Medicine (S.R.L.), Kings County Hospital Center, Brooklyn, NY; Department of Neurology (N.S.), University of Southern California, Los Angeles, CA; Department of Emergency Medicine (Sidney Starkman), University of California, Los Angeles, CA; Stroke Center (Sidney Starkman, D.L., K.S., L.K.S., J.L.S.), Department of Neurology, University of California, Los Angeles, CA; Department of Biomathematics (J.A.G.), David Geffen School of Medicine at UCLA, Los Angeles, CA; Department of Emergency Medicine (Samuel Stratton), Harbor-University of California, Los Angeles Medical Center, LA; Los Angeles EMS Agency (Samuel Stratton), Los Angeles, CA; Orange County EMS Agency (Samuel Stratton), Orange County, CA; Department of Emergency Medicine (M.E.), University of Southern California, Los Angeles, CA; Los Angeles Fire Department (M.E.), Los Angeles, CA; Department of Neurology (S.H.), Stanford University, Stanford, CA; and National Institute of Neurological Disorders and Stroke (R.C.), National Institutes of Health, Bethesda, MD.
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Sidney Starkman
From the Department of Neurology (C.B.), Neurocritical Care Division, NYU Langone Medical Center, Bellevue Hospital, New York, NY; Department of Neurology (S.R.L.), The State University of New York Downstate Medical Center, Brooklyn, NY & the Jaffe Stroke Center, Maimonides Medical Center, Brooklyn, NY; Department of Neurology and Emergency Medicine (S.R.L.), Kings County Hospital Center, Brooklyn, NY; Department of Neurology (N.S.), University of Southern California, Los Angeles, CA; Department of Emergency Medicine (Sidney Starkman), University of California, Los Angeles, CA; Stroke Center (Sidney Starkman, D.L., K.S., L.K.S., J.L.S.), Department of Neurology, University of California, Los Angeles, CA; Department of Biomathematics (J.A.G.), David Geffen School of Medicine at UCLA, Los Angeles, CA; Department of Emergency Medicine (Samuel Stratton), Harbor-University of California, Los Angeles Medical Center, LA; Los Angeles EMS Agency (Samuel Stratton), Los Angeles, CA; Orange County EMS Agency (Samuel Stratton), Orange County, CA; Department of Emergency Medicine (M.E.), University of Southern California, Los Angeles, CA; Los Angeles Fire Department (M.E.), Los Angeles, CA; Department of Neurology (S.H.), Stanford University, Stanford, CA; and National Institute of Neurological Disorders and Stroke (R.C.), National Institutes of Health, Bethesda, MD.
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David Liebeskind
From the Department of Neurology (C.B.), Neurocritical Care Division, NYU Langone Medical Center, Bellevue Hospital, New York, NY; Department of Neurology (S.R.L.), The State University of New York Downstate Medical Center, Brooklyn, NY & the Jaffe Stroke Center, Maimonides Medical Center, Brooklyn, NY; Department of Neurology and Emergency Medicine (S.R.L.), Kings County Hospital Center, Brooklyn, NY; Department of Neurology (N.S.), University of Southern California, Los Angeles, CA; Department of Emergency Medicine (Sidney Starkman), University of California, Los Angeles, CA; Stroke Center (Sidney Starkman, D.L., K.S., L.K.S., J.L.S.), Department of Neurology, University of California, Los Angeles, CA; Department of Biomathematics (J.A.G.), David Geffen School of Medicine at UCLA, Los Angeles, CA; Department of Emergency Medicine (Samuel Stratton), Harbor-University of California, Los Angeles Medical Center, LA; Los Angeles EMS Agency (Samuel Stratton), Los Angeles, CA; Orange County EMS Agency (Samuel Stratton), Orange County, CA; Department of Emergency Medicine (M.E.), University of Southern California, Los Angeles, CA; Los Angeles Fire Department (M.E.), Los Angeles, CA; Department of Neurology (S.H.), Stanford University, Stanford, CA; and National Institute of Neurological Disorders and Stroke (R.C.), National Institutes of Health, Bethesda, MD.
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Jeffrey A. Gornbein
From the Department of Neurology (C.B.), Neurocritical Care Division, NYU Langone Medical Center, Bellevue Hospital, New York, NY; Department of Neurology (S.R.L.), The State University of New York Downstate Medical Center, Brooklyn, NY & the Jaffe Stroke Center, Maimonides Medical Center, Brooklyn, NY; Department of Neurology and Emergency Medicine (S.R.L.), Kings County Hospital Center, Brooklyn, NY; Department of Neurology (N.S.), University of Southern California, Los Angeles, CA; Department of Emergency Medicine (Sidney Starkman), University of California, Los Angeles, CA; Stroke Center (Sidney Starkman, D.L., K.S., L.K.S., J.L.S.), Department of Neurology, University of California, Los Angeles, CA; Department of Biomathematics (J.A.G.), David Geffen School of Medicine at UCLA, Los Angeles, CA; Department of Emergency Medicine (Samuel Stratton), Harbor-University of California, Los Angeles Medical Center, LA; Los Angeles EMS Agency (Samuel Stratton), Los Angeles, CA; Orange County EMS Agency (Samuel Stratton), Orange County, CA; Department of Emergency Medicine (M.E.), University of Southern California, Los Angeles, CA; Los Angeles Fire Department (M.E.), Los Angeles, CA; Department of Neurology (S.H.), Stanford University, Stanford, CA; and National Institute of Neurological Disorders and Stroke (R.C.), National Institutes of Health, Bethesda, MD.
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Kristina Shkirkova
From the Department of Neurology (C.B.), Neurocritical Care Division, NYU Langone Medical Center, Bellevue Hospital, New York, NY; Department of Neurology (S.R.L.), The State University of New York Downstate Medical Center, Brooklyn, NY & the Jaffe Stroke Center, Maimonides Medical Center, Brooklyn, NY; Department of Neurology and Emergency Medicine (S.R.L.), Kings County Hospital Center, Brooklyn, NY; Department of Neurology (N.S.), University of Southern California, Los Angeles, CA; Department of Emergency Medicine (Sidney Starkman), University of California, Los Angeles, CA; Stroke Center (Sidney Starkman, D.L., K.S., L.K.S., J.L.S.), Department of Neurology, University of California, Los Angeles, CA; Department of Biomathematics (J.A.G.), David Geffen School of Medicine at UCLA, Los Angeles, CA; Department of Emergency Medicine (Samuel Stratton), Harbor-University of California, Los Angeles Medical Center, LA; Los Angeles EMS Agency (Samuel Stratton), Los Angeles, CA; Orange County EMS Agency (Samuel Stratton), Orange County, CA; Department of Emergency Medicine (M.E.), University of Southern California, Los Angeles, CA; Los Angeles Fire Department (M.E.), Los Angeles, CA; Department of Neurology (S.H.), Stanford University, Stanford, CA; and National Institute of Neurological Disorders and Stroke (R.C.), National Institutes of Health, Bethesda, MD.
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Samuel Stratton
From the Department of Neurology (C.B.), Neurocritical Care Division, NYU Langone Medical Center, Bellevue Hospital, New York, NY; Department of Neurology (S.R.L.), The State University of New York Downstate Medical Center, Brooklyn, NY & the Jaffe Stroke Center, Maimonides Medical Center, Brooklyn, NY; Department of Neurology and Emergency Medicine (S.R.L.), Kings County Hospital Center, Brooklyn, NY; Department of Neurology (N.S.), University of Southern California, Los Angeles, CA; Department of Emergency Medicine (Sidney Starkman), University of California, Los Angeles, CA; Stroke Center (Sidney Starkman, D.L., K.S., L.K.S., J.L.S.), Department of Neurology, University of California, Los Angeles, CA; Department of Biomathematics (J.A.G.), David Geffen School of Medicine at UCLA, Los Angeles, CA; Department of Emergency Medicine (Samuel Stratton), Harbor-University of California, Los Angeles Medical Center, LA; Los Angeles EMS Agency (Samuel Stratton), Los Angeles, CA; Orange County EMS Agency (Samuel Stratton), Orange County, CA; Department of Emergency Medicine (M.E.), University of Southern California, Los Angeles, CA; Los Angeles Fire Department (M.E.), Los Angeles, CA; Department of Neurology (S.H.), Stanford University, Stanford, CA; and National Institute of Neurological Disorders and Stroke (R.C.), National Institutes of Health, Bethesda, MD.
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Marc Eckstein
From the Department of Neurology (C.B.), Neurocritical Care Division, NYU Langone Medical Center, Bellevue Hospital, New York, NY; Department of Neurology (S.R.L.), The State University of New York Downstate Medical Center, Brooklyn, NY & the Jaffe Stroke Center, Maimonides Medical Center, Brooklyn, NY; Department of Neurology and Emergency Medicine (S.R.L.), Kings County Hospital Center, Brooklyn, NY; Department of Neurology (N.S.), University of Southern California, Los Angeles, CA; Department of Emergency Medicine (Sidney Starkman), University of California, Los Angeles, CA; Stroke Center (Sidney Starkman, D.L., K.S., L.K.S., J.L.S.), Department of Neurology, University of California, Los Angeles, CA; Department of Biomathematics (J.A.G.), David Geffen School of Medicine at UCLA, Los Angeles, CA; Department of Emergency Medicine (Samuel Stratton), Harbor-University of California, Los Angeles Medical Center, LA; Los Angeles EMS Agency (Samuel Stratton), Los Angeles, CA; Orange County EMS Agency (Samuel Stratton), Orange County, CA; Department of Emergency Medicine (M.E.), University of Southern California, Los Angeles, CA; Los Angeles Fire Department (M.E.), Los Angeles, CA; Department of Neurology (S.H.), Stanford University, Stanford, CA; and National Institute of Neurological Disorders and Stroke (R.C.), National Institutes of Health, Bethesda, MD.
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Scott Hamilton
From the Department of Neurology (C.B.), Neurocritical Care Division, NYU Langone Medical Center, Bellevue Hospital, New York, NY; Department of Neurology (S.R.L.), The State University of New York Downstate Medical Center, Brooklyn, NY & the Jaffe Stroke Center, Maimonides Medical Center, Brooklyn, NY; Department of Neurology and Emergency Medicine (S.R.L.), Kings County Hospital Center, Brooklyn, NY; Department of Neurology (N.S.), University of Southern California, Los Angeles, CA; Department of Emergency Medicine (Sidney Starkman), University of California, Los Angeles, CA; Stroke Center (Sidney Starkman, D.L., K.S., L.K.S., J.L.S.), Department of Neurology, University of California, Los Angeles, CA; Department of Biomathematics (J.A.G.), David Geffen School of Medicine at UCLA, Los Angeles, CA; Department of Emergency Medicine (Samuel Stratton), Harbor-University of California, Los Angeles Medical Center, LA; Los Angeles EMS Agency (Samuel Stratton), Los Angeles, CA; Orange County EMS Agency (Samuel Stratton), Orange County, CA; Department of Emergency Medicine (M.E.), University of Southern California, Los Angeles, CA; Los Angeles Fire Department (M.E.), Los Angeles, CA; Department of Neurology (S.H.), Stanford University, Stanford, CA; and National Institute of Neurological Disorders and Stroke (R.C.), National Institutes of Health, Bethesda, MD.
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Robin Conwit
From the Department of Neurology (C.B.), Neurocritical Care Division, NYU Langone Medical Center, Bellevue Hospital, New York, NY; Department of Neurology (S.R.L.), The State University of New York Downstate Medical Center, Brooklyn, NY & the Jaffe Stroke Center, Maimonides Medical Center, Brooklyn, NY; Department of Neurology and Emergency Medicine (S.R.L.), Kings County Hospital Center, Brooklyn, NY; Department of Neurology (N.S.), University of Southern California, Los Angeles, CA; Department of Emergency Medicine (Sidney Starkman), University of California, Los Angeles, CA; Stroke Center (Sidney Starkman, D.L., K.S., L.K.S., J.L.S.), Department of Neurology, University of California, Los Angeles, CA; Department of Biomathematics (J.A.G.), David Geffen School of Medicine at UCLA, Los Angeles, CA; Department of Emergency Medicine (Samuel Stratton), Harbor-University of California, Los Angeles Medical Center, LA; Los Angeles EMS Agency (Samuel Stratton), Los Angeles, CA; Orange County EMS Agency (Samuel Stratton), Orange County, CA; Department of Emergency Medicine (M.E.), University of Southern California, Los Angeles, CA; Los Angeles Fire Department (M.E.), Los Angeles, CA; Department of Neurology (S.H.), Stanford University, Stanford, CA; and National Institute of Neurological Disorders and Stroke (R.C.), National Institutes of Health, Bethesda, MD.
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Latisha K. Sharma
From the Department of Neurology (C.B.), Neurocritical Care Division, NYU Langone Medical Center, Bellevue Hospital, New York, NY; Department of Neurology (S.R.L.), The State University of New York Downstate Medical Center, Brooklyn, NY & the Jaffe Stroke Center, Maimonides Medical Center, Brooklyn, NY; Department of Neurology and Emergency Medicine (S.R.L.), Kings County Hospital Center, Brooklyn, NY; Department of Neurology (N.S.), University of Southern California, Los Angeles, CA; Department of Emergency Medicine (Sidney Starkman), University of California, Los Angeles, CA; Stroke Center (Sidney Starkman, D.L., K.S., L.K.S., J.L.S.), Department of Neurology, University of California, Los Angeles, CA; Department of Biomathematics (J.A.G.), David Geffen School of Medicine at UCLA, Los Angeles, CA; Department of Emergency Medicine (Samuel Stratton), Harbor-University of California, Los Angeles Medical Center, LA; Los Angeles EMS Agency (Samuel Stratton), Los Angeles, CA; Orange County EMS Agency (Samuel Stratton), Orange County, CA; Department of Emergency Medicine (M.E.), University of Southern California, Los Angeles, CA; Los Angeles Fire Department (M.E.), Los Angeles, CA; Department of Neurology (S.H.), Stanford University, Stanford, CA; and National Institute of Neurological Disorders and Stroke (R.C.), National Institutes of Health, Bethesda, MD.
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Jeffrey L. Saver
From the Department of Neurology (C.B.), Neurocritical Care Division, NYU Langone Medical Center, Bellevue Hospital, New York, NY; Department of Neurology (S.R.L.), The State University of New York Downstate Medical Center, Brooklyn, NY & the Jaffe Stroke Center, Maimonides Medical Center, Brooklyn, NY; Department of Neurology and Emergency Medicine (S.R.L.), Kings County Hospital Center, Brooklyn, NY; Department of Neurology (N.S.), University of Southern California, Los Angeles, CA; Department of Emergency Medicine (Sidney Starkman), University of California, Los Angeles, CA; Stroke Center (Sidney Starkman, D.L., K.S., L.K.S., J.L.S.), Department of Neurology, University of California, Los Angeles, CA; Department of Biomathematics (J.A.G.), David Geffen School of Medicine at UCLA, Los Angeles, CA; Department of Emergency Medicine (Samuel Stratton), Harbor-University of California, Los Angeles Medical Center, LA; Los Angeles EMS Agency (Samuel Stratton), Los Angeles, CA; Orange County EMS Agency (Samuel Stratton), Orange County, CA; Department of Emergency Medicine (M.E.), University of Southern California, Los Angeles, CA; Los Angeles Fire Department (M.E.), Los Angeles, CA; Department of Neurology (S.H.), Stanford University, Stanford, CA; and National Institute of Neurological Disorders and Stroke (R.C.), National Institutes of Health, Bethesda, MD.
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Neurologic Improvement in Acute Cerebral Ischemia
Frequency, Magnitude, Predictors, and Clinical Outcomes
Clotilde Balucani, Steven R. Levine, Nerses Sanossian, Sidney Starkman, David Liebeskind, Jeffrey A. Gornbein, Kristina Shkirkova, Samuel Stratton, Marc Eckstein, Scott Hamilton, Robin Conwit, Latisha K. Sharma, Jeffrey L. Saver
Neurology Mar 2023, 100 (10) e1038-e1047; DOI: 10.1212/WNL.0000000000201656

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Abstract

Background and Objectives Investigations of rapid neurologic improvement (RNI) in patients with acute cerebral ischemia (ACI) have focused on RNI occurring after hospital arrival. However, with stroke routing decisions and interventions increasingly migrating to the prehospital setting, there is a need to delineate the frequency, magnitude, predictors, and clinical outcomes of patients with ACI with ultra-early RNI (U-RNI) in the prehospital and early postarrival period.

Methods We analyzed prospectively collected data of the prehospital Field Administration of Stroke Therapy–Magnesium (FAST-MAG) randomized clinical trial. Any U-RNI was defined as improvement by 2 or more points on the Los Angeles Motor Scale (LAMS) score between the prehospital and early post–emergency department (ED) arrival examinations and classified as moderate (2–3 point) or dramatic (4–5 point) improvement. Outcome measures included excellent recovery (modified Rankin Scale [mRS] score 0–1) and death by 90 days.

Results Among the 1,245 patients with ACI, the mean age was 70.9 years (SD 13.2); 45% were women; the median prehospital LAMS was 4 (interquartile range [IQR] 3–5); the median last known well to ED-LAMS time was 59 minutes (IQR 46–80 minutes), and the median prehospital LAMS to ED-LAMS time was 33 minutes (IQR 28–39 minutes). Overall, any U-RNI occurred in 31%, moderate U-RNI in 23%, and dramatic U-RNI in 8%. Any U-RNI was associated with improved outcomes, including excellent recovery (mRS score 0–1) at 90 days 65.1% (246/378) vs 35.4% (302/852), p < 0.0001; decreased mortality by 90 days 3.7% (14/378) vs 16.4% (140/852), p < 0.0001; decreased symptomatic intracranial hemorrhage 1.6% (6/384) vs 4.6% (40/861), p = 0.0112; and increased likelihood of being discharged home 56.8% (218/384) vs 30.2% (260/861), p < 0.0001.

Discussion U-RNI occurs in nearly 1 in 3 ambulance-transported patients with ACI and is associated with excellent recovery and decreased mortality at 90 days. Accounting for U-RNI may be useful for routing decisions and future prehospital interventions.

Trial Registration Information clinicaltrials.gov. Unique identifier: NCT00059332.

Glossary

ACI=
acute cerebral ischemia;
ASPECTS=
Alberta Stroke Program Early CT Score;
ED=
emergency department;
IV t-PA=
IV tissue plasminogen activator;
LAMS=
Los Angeles Motor Scale;
LKW=
last known well;
mRS=
modified Rankin Scale;
NIHSS=
NIH Stroke Scale;
ROC=
receiver operator characteristic curve;
SICH=
symptomatic intracranial hemorrhage;
U-RNI=
ultra-early rapid neurologic improvement

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Submitted and externally peer reviewed. The handling editor was Editor-in-Chief José Merino, MD, MPhil, FAAN.

  • Received January 27, 2022.
  • Accepted in final form October 20, 2022.
  • © 2022 American Academy of Neurology
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