急性缺血性腦中風靜脈血栓溶解治療

Intravenous Thrombolysis for Acute Ischemic Stroke

自從1995年血栓溶解治療被證實有助於改善急性腦梗塞病人的神經復原，而且不會顯著增加死亡率，急性腦梗塞的治療已被徹底的改變。但許多臨床狀況，包括治療區間僅為發作3小時內，及許多臨床禁忌症（如年齡大於80歲等），限制了該治療的運用對象，約只有5％的急性腦梗塞病人有機會接受此治療。2008年的臨床試驗證實針對發作3至4.5小時的急性腦梗塞病人，施行血栓溶解治療仍具有療效後，治療的時間窗延長到發作後4.5小時內。急性腦梗塞的再灌流治療在2015年獲得進一步突破，當年多篇跨國多中心研究證實了橋接治療的再灌流療法的療效。橋接治療包括對於符合條件的急性腦梗塞病人，先施行靜脈血栓溶解治療，再為大動脈阻塞的病人施以動脈血栓移除術。2018年的研究證實經磁振造影或電腦斷層灌流影像確定有相當範圍可挽救腦組織的情形下，可以在發作16－24小時內施行動脈血栓移除治療，有效改善病人的預後。「治療組織窗」的觀念使用「臨床－影像不對等」或是「灌流－擴散影像不對等」的臨床及影像評估篩選出有相當可挽救腦組織體積的病人，執行再灌流治療，打破了傳統只利用「治療時間窗」決定治療的概念。最近發表的研究運用相同腦部「灌流－擴散影像不對等」的概念，將靜脈血栓溶解治療用於發作時間不明（或睡醒時被發現），或發作時間4.5－9小時內的急性腦梗塞病人，可能有臨床改善的效果。「時間就是大腦」的觀念以「治療時間窗」提醒醫療人員及社會大眾急性中風需要緊急的偵測、處置與治療，但是「治療組織窗』的觀念也讓我們對於發作時間不明或比較晚發現送到醫院的病人，可以運用臨床症狀及腦部影像不對等的方式篩選出適當的病人，考慮進一步施行腦部再灌流治療，造福更多的病人。

Intravenous recombinant tissue plasminogen activator (tPA) has been documented to be effective for neurological functional recovery of patients with acute cerebral infarct since 1995, without increasing mortality. However, the effect declines overtime and the application was limited by the time windows of 3 hours and by clinical contraindications, including ages older than 80 years. The therapeutic time window has been extended to 4.5 hours since 2008. Further break-through of reperfusion therapy of acute cerebral infarct has been achieved by bridging therapy with intravenous tPA, followed by endovascular thrombectomy with stent or suction retrievers documented in 2015. It prompts the revision of American Heart Association/American Stroke Association guidelines for early management of patients with acute ischemic stroke. The therapeutic time windows for endovascular thrombectomy has been further extended up to 16-24 hours by positive results of the studies in 2017 and 2018 with appropriate survey demonstrating large salvageable brain volumes by applying either clinical-imaging mismatch or perfusion-diffusion mismatch concept. The successful extension of endovascular thrombectomy supports patients with penumbra might still benefit from reperfusion therapy beyond the previously defined “time window”. The “tissue window” concept could also apply for intravenous tPA by the results of two recently published randomized control trials. Efficacy and Safety of MRI-based Thrombolysis in Wake-Up Stroke (WAKE-UP) trial recruited patients with unknown time of onset of stroke having mismatch between diffusion-weighted imaging and fluid-attenuated inversion recovery (FLAIR) imaging, and Extending the Time for Thrombolysis in Emergency Neurological Deficits (EXTEND) trial recruited patients with 4.5-9 hours of onset or those with stroke on awakening within 9 hours from midpoint of sleep. “Time is Brain” makes us recognize the stroke needs emergent attention, evaluation and treatment, but “tissue window” concept awakes us that opportunity may still exist for better functional recovery of acute stroke patients when they present late or even were noticed on wakening up.