頸動脈粥狀性硬化疾病患者於血管再通暢術後其腦部血液灌流變化與神經認知功能改變之關聯

The Relationship between the Change of Brain Perfusion and Neurocognitive Function after Carotid Revascularization in the Patients with Carotid Atherosclerotic disease

林茂欣(Mao-Shin Lin)

指導教授 ： 陳明豐

國立臺灣大學/醫學院/臨床醫學研究所/博士(2015年)

https://doi.org/10.6342/NTU.2015.00906

摘要

對於內頸動脈狹窄的病患，頸動脈內膜切除術及頸動脈支架置放術已被證實可有效降低缺血性腦中風的風險。除了缺血性腦中風及短暫缺血性事件這兩個治療標的以外，近年來越來越多人開始將焦點關注於病患的神經認知功能。流行病學研究追蹤頸動脈狹窄的病患後發現，只有左側頸動脈狹窄的病患會合併認知功能的缺陷及下降，但右側狹窄者較不會。 一些極端的案例如頸動脈完全阻塞的病患，縱使過去從未有腦中風的臨床病史，同樣明顯發現有認知功能的缺陷。許多人直覺得推斷，透過現有的治療方式包括頸動脈內膜切除術及頸動脈支架置放術等，移除血管中的狹窄或阻塞以恢復腦部的正常血液灌流，應該會對病患的認知功能有正面的影響。但有趣的是後續諸多神經認知功能研究的結果卻無法獲得一致的結論，有些認為頸動脈再通暢手術對認知功能有幫助，有些卻認為無助於認知功能的進步，甚至有害。本研究將探討對於頸動脈疾病患者，頸動脈支架置放術在神經認知功能的影響到底為何，並嘗試去尋找是否有特定的族群病患才能從此一術式中獲益。另外，我們將利用18F-fluorodeoxyglucose (FDG) 正子放射型電腦斷層攝影(positron emission tomography, PET)來偵側腦部的代謝狀況，以進一步確認頸動脈支架置放術是否能改善腦部代謝。
首先，我們先從探討支架置放術對於頸動脈慢性全阻塞病人的臨床效益為開始，以認知功能改變做為評估的臨床終點。我們發現相較於術式失敗的病人(N=7)，成功的術式(N=12)確實能改善整體的神經認知功能，尤其是注意力及精神運動處理能力。我們隨後將此一研究模式擴及至所有頸動脈狹窄應接受支架置放術的病患身上，並且根據其術前腦部血液灌流狀況及術式結果予以分組並分析，試圖去進一步了解腦部血液灌流變化在術前術後對認知功能的影響，以釐清過去諸多研究的盲點所在。我們發現成功的術式確實可改善病患的神經認知功能，但只侷限於術前腦部血液灌流不足的病人身上。術前術後神經認知功能的變化與腦部血液灌流的變化有一定程度的關聯。這結果顯示缺血的大腦半球經血管再通暢手術後，其神經認知功能可呈現可逆的反應。最後，借助FDG PET的幫忙，我們發現病患若所接受的術式成功，其腦部代謝狀況的預後較那些術式失敗者來的好。頸動脈治療後，其相對應的腦部區域代謝狀況大多獲得改善，可能是導因於腦部血液灌流的改善。
總結，我們的研究發現對於嚴重頸動脈狹窄或阻塞且合併腦部血液灌流不足的病人，成功的頸動脈支架置放術不僅可以改善神經認知功能之預後，還能增進腦部的代謝狀況。

關鍵字

內頸動脈狹窄 ； 內頸動脈完全阻塞 ； 頸動脈支架 ； 血管性失智 ； 神經認知功能

並列摘要

Reducing embolic stroke by carotid artery stenting (CAS) and carotid endarterectomy (CEA) in patients with severe internal carotid occlusive disease has been well proven. Neurocognitive function is being increasingly recognized as an important outcome measure. Cognitive impairment and decline were found in patients with asymptomatic high-grade stenosis of the left internal carotid artery (ICA), and hypoperfusion may be a potential cause. It is intuitive that reopening a stenotic vessel and restoring blood flow to the brain would certainly have favorable neurocognitive effects, but previous studies have provided inconsistent results. In this study, we explored the effect of CAS on neurocognitive function in patients with severe carotid artery occlusive disease and tried to find out the specific population who will benefit from the procedure. By using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to assess brain metabolism, we would also like to demonstrate the metabolic improvement following successful CAS.
First of all, we investigated the cognitive effect of successful CAS in patients with chronic internal carotid artery occlusion (ICAO) and ipsilateral cerebral ischemia. As compared to the failed group (N=7), we found that successful CAS (N=12) improved global cognitive function as well as attention and psychomotor processing speed in patients with chronic ICAO. For further proving the effect of CAS on neurocognitive function in patients with severe carotid artery occlusive disease, we expanded patient cohort to assess the neurocognitive change after CAS in all patients with severe ICA disease, analyzed according to baseline perfusion status of ipsilateral hemisphere and procedure result. We also found that successful CAS can improve global cognitive functions in patients with ICA stenosis/occlusion, but only in patients with baseline objective abnormal cerebral perfusion. The changes of cognitive function are correlated with the change of brain perfusion. The results imply the reversibility of cognitive function in ischemic hemisphere after restoring cerebral perfusion. With the assist of FDG PET, we observed that patients who underwent successful CAS had superior brain metabolism outcomes by comparison to those with failed recanalization. The improvement of brain FDG observed in areas corresponding to the treated ICA territory could be due to the restored perfusion.
In summary, successful CAS not only improves neurocognitive outcome but also improves cerebral glucose metabolism in patients with objectively-assessed cerebral ischemia due to severe chronic carotid stenosis or occlusion.

並列關鍵字

Carotid stenosis ； carotid occlusion ； carotid stenting ； vascular dementia ； neurocognitive function

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