Title: Magnesium, another failed neuroprotectant?
題目：鎂，另一個失敗的神經保護劑？
Author: Wan-Tsu Wendy Chang
作者：Wan-Tsu Wendy Chang
翻譯：江利冰 校對：肖鋒

Stroke is a leading cause of adult disability and the second leading cause of death worldwide. Currently available therapies for acute ischemic stroke are based on restoring perfusion to the ischemic penumbra. However, they are only moderately effective.
中風是成年人首位致殘原因同時也是第二位死亡原因。對于急性缺血性中風目前的治療策略均是基于恢復缺血半暗區的再灌注。但是這些策略僅僅具有中等療效。

A series of pathological cascades leading to neuronal death are triggered in acute ischemia. Thus it may be logical to suggest that if one can interrupt the propagation of these cascades, perhaps part of the brain tissue can be protected and salvaged.
在急性缺血過程中，會激發一系列導致神經元死亡的病理性瀑布反應。因此，如果能夠中斷這些病理性瀑布，就有可能保護和搶救部分神經元。

Magnesium has been shown in various animal models to have pluripotent neuroprotective properties. It is also widely available, simple to administer, and has a favorable risk profile. A prior study of magnesium in acute ischemic stroke (IMAGES) did not show a benefit when the agent was administered a median 7.4 hours after symptom onset. However, a subgroup of patients treated within 3 hours of symptom onset showed possible benefit.
鎂在很多動物模型中已經顯示出了多功能的神經保護特性。它來源廣泛，使用簡單而且使用安全。之前一項報道(IMAGES)研究了在急性缺血中風中使用鎂，發現當在癥狀出現后的7.4個小時后使用鎂，沒有顯示出任何優勢。然而亞組分析中當在癥狀出現3個小時內使用鎂時，患者可能會受益。

The Field Administration of Stroke Therapy - Magnesium (FAST-MAG) trial, funded by the NIH, looked at magnesium administered within 2 hours after symptom onset on the degree of disability at 90 days after stroke as measured by the modified Rankin scale.
FAST-MAG研究是NIH資助的一項的研究，主要研究在中風癥狀出現后2個小時內使用鎂對中風患者90天功能障礙的影響，使用改良Rankin評分表示。
• A total of 1700 patients were included in the study.
• 該研究共納入了1700例患者。
• 73.3% of patients had a final diagnosis of ischemic stroke, compared with 22.8% with intracranial hemorrhage and 3.9% with stroke-mimicking condition.
• 73.3%患者最終診斷為缺血性中風，22.8%的患者存在顱內出血，3.9%的患者為類中風情況。
• Of the patients with ischemic stroke, 52.4% were treated with tPA.
• 對于缺血性中風的患者，52.4%的患者接受了組織纖溶酶原激活劑的治療

Magnesium was not found to have any benefit in functional outcome at 90 days.
鎂對中風患者90天的功能恢復沒有任何的益處。

This study was unique in several ways:
這個研究在一些方面是獨一無二的：

It examined the use of a neuroprotective agent in the hyperacute window of 2 hours, as a common criticism of prior neuroprotective studies is that those agents may not have been administered within the optimal therapeutic window
該研究探查了在超急性期（2h內）使用神經保護劑的作用，否定了之前研究認為神經保護劑沒有在最佳的治療窗內使用的說法。
Administration of the neuroprotective agent began in the prehospital setting. Logistically, this was done with a pre-randomized study kit containing the initial bolus dose to be administered by EMS and the maintenance dose to be given to the receiving hospital for administration in the ED.
在院前開始使用神經保護劑。初始計量在院前由EMS工作人員提供，維持劑量在入院后，急診室內給予。
Despite the short window for enrollment and drug administration, patients were screened using a previously validated prehospital stroke scale and 98.7% of patients were enrolled after explicit written informed consent from the patient or a legally authorized representative.
盡管患者納入以及藥物使用的窗口期很短，患者篩選使用的是經過驗證的院前中風量表，而且98.7%的患者或者合法授權代理人簽署了知情同意書。

However, despite this study being very well executed, demonstrating the feasibility of conducting a phase 3 trial with targeted intervention within the hyperacute window, it is another neuroprotective agent that failed to translate from the laboratory bench to the clinical realm.
但是，盡管該研究執行的很嚴謹，預示著在超急性期使用目標干預的3期臨床試驗的可行性，但是也說明了另一種神經保護劑無法從實驗室的療效轉化為臨床療效。
Potential explanations for the discrepancies between preclinical and clinical outcomes of neuroprotective agents thus far include discrepancies on outcome measures, functional assessments, pre-morbid conditions, therapeutic windows, and drug-dosing schedules between animal studies and clinical trials.
目前可以解釋臨床前期和臨床研究結果矛盾的原因包括：結局測量指標的不同、功能評估的方法、發病前的基礎疾病、治療窗以及動物實驗和臨床研究之間不同的藥物劑量時間表。

Take Home Point: Magnesium does not have any clear benefit in acute ischemic stroke at this time.
要點：目前鎂對于急性缺血性中風還沒有發現任何明顯的益處。