接受深腦刺激術之巴金森病患者其認知功能與凝凍步態之關聯性

Abstract

研究背景：深腦刺激術能夠有效改善巴金森病病患的運動症狀並且減輕與左旋多巴相關的併發症。凝凍步態是常見的巴金森病運動症狀之一，容易造成病患跌倒與失能，但每個病人的凝凍步態對藥物和深腦刺激術的反應皆不同，其治療對臨床醫師來說仍是重大挑戰。凝凍步態的致病機轉現仍不明，有研究指出與解決動作衝突相關的執行功能有所缺陷會造成凝凍步態，也有研究指出凝凍步態是因為在基底核的運動、認知與邊緣系統之神經網絡不協調所致。然而，在接受深腦刺激術的巴金森病人族群中，其認知功能對於術後凝凍步態改善程度的影響仍不清楚。本研究旨在分析台灣巴金森病患者接受深腦刺激術治療後，其認知功能與凝凍步態的關聯性。 研究方法：本研究收錄在台大醫院接受深腦刺激術治療的巴金森病患且是在2015到2021年間在本院有完整術後巴金森症狀評估與認知功能檢查的病人，關於疾病發作和狀態、運動和非運動症狀狀態、藥物使用情況、左旋多巴等效劑量、術前和術後的簡易精神狀態檢查(MMSE)，以及深腦刺激術的設定皆有完整的紀錄。運動和非運動症狀狀態使用UPDRS巴金森症狀衡量表中文版進行測量。共計納入50位巴金森病患者，並根據他們在深腦刺激術開啟刺激期間的凝凍步態改善情況分為兩組，包含29名凝凍步態改善組和21名凝凍步態無效組。 研究結果：凝凍步態改善組在術後追蹤之簡易精神狀態檢查(MMSE)總分有顯著下降。兩組患者在發病年齡、接受深腦刺激術之治療年齡、疾病持續時間、潛在疾病、教育程度、術前Hoehr和Yahr分期、術前UPDRS第三部分分數、術前MMSE及BDI憂鬱量表方面無顯著差異。凝凍步態改善組有較高比例之年輕發病型巴金森病患者與和較高的術前姿態不穩與步態困難(PIGD)分數，但其術後UPDRS第一部分的思想項目分數較低。凝凍步態改善組在術後12個月和48個月追蹤期間的左旋多巴等效劑量也有顯著的降低。 結論：本篇研究發現相較於深腦刺激術術後凝凍步態未改善之病患，術後凝凍步態改善的病人在術後追蹤期間其認知功能的減退更為明顯，其中凝凍步態改善組病患有較嚴重的姿態不穩與步態困難(PIGD)分數。在臨床上，我們需要更加注意有凝凍步態之巴金森病患者的認知功能，可能有較高比例出現失智症，需要安排更全面性的認知功能檢查且定期追蹤。

Background: Deep brain stimulation (DBS) of the subthalamic nucleus is an effective treatment for advanced Parkinson’s disease (PD) to improve motor symptoms and ameliorate levodopa-related complications. Freezing of gait (FOG) is a common, disabling symptom of PD, but the treatment of FOG remains a significant challenge for clinicians. Some theoretical mechanisms of FOG emphasize a deficit in executive function related to conflict resolution and the incoordination of the neural network between motor, cognitive, and limbic pathways. However, the influence of cognitive function on the treatment response of deep brain stimulation for FOG is controversial. The aim of our study is to analyze the relationship between cognition and FOG in patients with PD receiving DBS therapy in the Taiwanese Parkinson’s disease population. Methods: We enrolled the patients with advanced Parkinson’s disease who underwent deep brain stimulation in National Taiwan University Hospital and with complete follow-up motor function and cognition during 2015-2021. We collect their disease onset and status, motor and non-motor symptoms state, medication, levodopa equivalent dosage (LEDD), preoperative and postoperative Mini-Mental State Examination (MMSE), and DBS stimulation setting. The motor and non-motor symptoms state was measured by Unified Parkinson's Disease Rating Scale (UPDRS). A total of 50 PD patients were enrolled and divided into two groups, 29 FOG responders and 21 FOG non-responders, based on their improvement of FOG during DBS on-stimulation, as measured by the UPDRS part II FOG score (item 14) during ON-stimulation/OFF-medication compared to the status during OFF-stimulation/OFF-medication. Results: The FOG responders had a significant decrease in MMSE between pre-operative and post-operative follow-up. There was no significant difference in the age of onset, age of receiving DBS, disease duration, underlying diseases, education, baseline Hoehr and Yahr stage, baseline UPDRS part III score, baseline MMSE score, and BDI score of two groups. The FOG responders presented higher rate of young-onset PD and higher subscore of pre-operative postural instability and gait difficulty (PIGD), but lower score of post-operative UPDRS part I thought item. The FOG responders also had significant lower levodopa equivalent daily dose in the post-operative 12- and 48-months follow-up. Conclusion: The results of this study show that the FOG responders of DBS therapy had more cognition decline compared to the FOG non-responders. The more comprehensive and regular cognition function follow-up is needed in the FOG responder group.