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Original Investigation
November 2018

Frequency, Predictors, and Outcomes of Prehospital and Early Postarrival Neurological Deterioration in Acute Stroke: Exploratory Analysis of the FAST-MAG Randomized Clinical Trial

Author Affiliations
  • 1Stroke Center, Department of Neurology, University of California, Los Angeles
  • 2Department of Emergency Medicine, University of California, Los Angeles
  • 3Department of Neurology, Stanford University, Stanford, California
  • 4Department of Emergency Medicine, University of Southern California, Los Angeles
  • 5Los Angeles Fire Department, Los Angeles, California
  • 6Department of Emergency Medicine, Harbor-University of California, Los Angeles Medical Center, Los Angeles
  • 7Los Angeles EMS Agency, Los Angeles, California
  • 8Orange County EMS Agency, Orange County, California
  • 9Los Angeles County Department of Public Health, Los Angeles, California
  • 10National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
  • 11Department of Neurology, University of Southern California, Los Angeles
JAMA Neurol. 2018;75(11):1364-1374. doi:10.1001/jamaneurol.2018.1893
Key Points

Question  What are the frequency, predictors, and outcomes of neurological deterioration in the ultra-early period after ischemic stroke and intracranial hemorrhage?

Findings  In this exploratory analysis of 1690 patients enrolled in the double-blind, placebo-controlled, randomized Field Administration of Stroke Therapy-Magnesium Trial, ultra-early neurological deterioration occurred in 1 in 3 patients with intracranial hemorrhage and in 1 in 16 patients with acute cerebral ischemia. Ultra-early neurological deterioration was associated with markedly reduced functional independence and increased mortality.

Meaning  Reducing ultra-early neurological deterioration during prehospital and early postarrival is an important target to improve outcomes among patients with acute stroke.

Abstract

Importance  Studies of neurological deterioration in stroke have focused on the subacute period, but stroke treatment is increasingly migrating to the prehospital setting, where the neurological course has not been well delineated.

Objective  To describe the frequency, predictors, and outcomes of neurological deterioration among patients in the ultra-early period following ischemic stroke or intracranial hemorrhage.

Design, Settings, and Participants  Exploratory analysis of the prehospital, randomized Field Administration of Stroke Therapy-Magnesium (FAST-MAG) Trial conducted from 2005 to 2013 within 315 ambulances and 60 stroke patient receiving hospitals in Southern California. Participants were consecutively enrolled patients with suspected acute stroke who were transported by ambulance within 2 hours of stroke onset.

Main Outcomes and Measures  The main outcome was neurological deterioration, defined as a worsening of 2 or more points on the Glasgow Coma Scale (GCS), a level of consciousness scale ranging from 3 to 15, with higher scores indicating more alertness. Imaging outcomes were ischemic or hemorrhagic injury extent identified during the first brain imaging scan. Outcomes at 3 months included global disability level (assessed using the modified Rankin Scale [mRS]; range, 0-6, with higher numbers indicating greater disability) and mortality.

Results  Among the 1690 patients (99.4%), the mean (SD) age was 69.4 (13.5) years, and 43% were female. Final diagnoses were acute cerebral ischemia in 1237 patients (73.2%), intracranial hemorrhage in 386 patients (22.8%), and neurovascular mimic in 67 patients (4.0%). The median (interquartile range [IQR]) minutes between the last well-known time and GCS assessments were 23 (14-42) minutes for prehospital, 58 (46-79) minutes for ED arrival, and 149 (120-180) minutes for early ED course assessments. From prehospital to early postarrival, ultra-early neurological deterioration (U-END) occurred in 200 of 1690 patients (11.8%), more often among patients with intracranial hemorrhage than among those with acute cerebral ischemia (119 of 386 [30.8%] vs 75 of 1237 [6.1%], P < .001). Patterns of U-END were prehospital U-END without early recovery in 30 of 965 patients (3.1%), stable prehospital course but early ED deterioration in 49 of 965 patients (5.1%), and continuous deterioration in both prehospital and early ED phases in 27 of 965 patients (2.8%). Ultra-early neurological deterioration was associated with worse 3-month outcomes, including increased global disability (mRS score, 4.6 vs 2.4; P < .001), reduced functional independence (mRS score 0-2, 32 of 200 [16.0%] vs 844 of 1490 [56.6%]; P < .001), and increased mortality (87 of 200 [43.5%] vs 176 of 1490 [11.8%]; P < .001).

Conclusions and Relevance  Ultra-early neurological deterioration occurs in 1 in 8 ambulance-transported patients with acute cerebrovascular disease, including 1 in 3 patients with intracranial hemorrhage and 1 in 16 patients with acute cerebral ischemia, and is associated with markedly reduced functional independence and increased mortality. Averting U-END may be a target for future prehospital therapeutics.

Trial Registration  ClinicalTrials.gov Identifier: NCT00059332

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