Is there diurnal variation in neuroprotective and thrombolytic therapy effect upon acute cerebral ischemia outcome?

IF 2 4区 医学 Q3 NEUROSCIENCES
Fatima Pariona-Vargas MD , Katherine T. Mun MD , Eng H. Lo PhD , Sidney Starkman MD , Nerses Sanossian MD , Mersedeh Bahr Hosseini MD , Samuel Stratton MD , Marc Eckstein MD , Robin A. Conwit MD , David S. Liebeskind MD , Latisha K. Sharma MD , Neal M. Rao MD , Kristina Shkirkova MD , Gilda Avila , May A. Kim-Tenser MD , Jeffrey L. Saver MD , FAST-MAG Investigators
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引用次数: 0

Abstract

Background

Preclinical studies have found marked diurnal/circadian variation in the effect of neuroprotective agents in acute ischemic stroke. However, the presence of diurnal variation in treatment outcomes after neuroprotective therapy has not been analyzed in human clinical trials and variation after thrombolytic therapy has been under-studied.

Methods

We analyzed patients with acute cerebral ischemia enrolled in the Field Administration of Stroke Therapy – Magnesium (FAST-MAG) randomized trial of magnesium sulfate started in the ambulance within two hours of stroke onset (last known well time). Patients with stroke onset times during daytime (07:00–22:59) and nighttime (23:00–06:59) were compared for variation in magnesium neuroprotective effect, thrombolysis effect, supportive care effect upon early neurologic course and three-month functional outcomes.

Results

Among 1235 acute cerebral ischemia patients, final diagnoses were acute ischemic stroke in 83.6 % and transient ischemic attack in 16.4 %. Time of onset was daytime in 1147 (92.8 %) and nighttime in 88 (7.2 %). Thrombolytic therapy was administered to 473 (38.3 %). Patients with night onset had longer onset to paramedic (median 32.5 vs 23 min); longer onset to Emergency Department arrival (median 70 vs 58 min); and higher prehospital systolic blood pressure (mean 162 vs 155 mm Hg). Among patients receiving thrombolysis, magnesium was associated with increased early neurological deterioration during night-time (50.0 % vs 23.1 %) but not day-time (21.1 % vs 22.4 %), p=0.03. However, no similar diurnal variation in magnesium or thrombolysis effects were noted for other early or three-month functional outcomes.

Conclusions

Among acute cerebral ischemia patients, efficacy, safety, neuroprotective agent, and thrombolytic response outcomes were largely unmodified by witnessed onset during active versus inactive phase clock times. These findings suggest biologic wake-sleep state rather than chronologic clock time is the driver of known circadian rhythmicity in stroke course.
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来源期刊
CiteScore
5.00
自引率
4.00%
发文量
583
审稿时长
62 days
期刊介绍: The Journal of Stroke & Cerebrovascular Diseases publishes original papers on basic and clinical science related to the fields of stroke and cerebrovascular diseases. The Journal also features review articles, controversies, methods and technical notes, selected case reports and other original articles of special nature. Its editorial mission is to focus on prevention and repair of cerebrovascular disease. Clinical papers emphasize medical and surgical aspects of stroke, clinical trials and design, epidemiology, stroke care delivery systems and outcomes, imaging sciences and rehabilitation of stroke. The Journal will be of special interest to specialists involved in caring for patients with cerebrovascular disease, including neurologists, neurosurgeons and cardiologists.
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