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研究生: 林伯睿
Lin, Bor-Ruey
論文名稱: 閉迴路深顱電刺激應用於大鼠癲癇抑制之長期效益分析
Long-term Follow-up of Closed-loop Deep Brain Electrical Stimulation on the Epileptic Rat Model for Seizure Control
指導教授: 梁勝富
Liang, Sheng-Fu
學位類別: 碩士
Master
系所名稱: 電機資訊學院 - 資訊工程學系
Department of Computer Science and Information Engineering
論文出版年: 2016
畢業學年度: 104
語文別: 英文
論文頁數: 60
中文關鍵詞: 癲癇癲癇偵測腦電圖腦部刺激閉迴路長時間實驗
外文關鍵詞: Epilepsy, seizure detection, electroencephalogram (EEG), brain stimulation, closed-loop, long-term
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  • 癲癇是常見的慢性神經系統疾病,世界上約有不到百分之一的人口患有這種疾病。然現有治療癲癇策略包括抗癲癇藥、切除性手術和迷走神經電刺激法。但仍有大約四分之一的癲癇患者沒有辦法透過現存的醫療技術有效的控制癲癇發作。癲癇發生的主因是來自腦部的不正常放電。因此腦電波自然成為觀察、偵測癲癇、甚至更進一步開發治療方法的最佳工具。而多項以腦電圖為基礎開發的閉迴路式腦部電刺激系統已被提出且付諸實行,目前NeuroPace的RNS system已於2013年通過美國食品藥物管理局認證。而Medtronic的the Intercept™ Epilepsy Control System則於2012年五月結束試驗並於2013年通過美國食品藥物管理局的認證列為第一級召回之醫療器材。在兩年的實驗中,過半的受試者的癲癇頻率減少超過50%,另有14名受試者6個月沒有癲癇發作。這篇論文中我們觀察長時間使用閉迴路式的電刺激抑制系統所造成的影響,實驗採用天生便患有失神性癲癇的Long-Evans大鼠。透過各星期大鼠腦波訊號的棘狀放電波特徵,將其量化成各式指標搭配統計分析,來說明使用閉迴路式電刺激抑制系統能有效益智老鼠癲癇發作。同時比對大腦切片,我們也發現給予電刺激會使大腦組織阻抗產生變化,細胞密度增加,在長時間裝載抑制系統後,即使電極因組織增生被包覆而提升,系統仍能夠有效抑制癲癇。經過四週的實驗之後,十隻實驗鼠平均的癲癇發作時間跟癲癇發作次數明顯減少;經過八週的實驗後,相較於第二週,有三隻實驗鼠的癲癇發作時間跟癲癇發作次數有更進一步的減少。

    Epilepsy is a chronic neurological disease which occurs about 0.8% of the world’s population. Current strategy for treating epilepsy includes medication, resective surgery and vagus nerve stimulation. In spite of these treatments, there are about a quarter of the patients are still suffer from uncontrollable seizure. Abnormal discharge in brain is what causing epilepsy to happen. Due to this fact, electroencephalogram (EEG) is the perfect tool to observe, measure, detect, and furthermore, develop treatment. Deep brain stimulation with close-loop control had already been proposed and put in practical; NeuroPace’s RNS has approved by FDA at November 2013. clinical trial. And another clinical trial of Medtronic’s InterceptTM finished at May 2012, with half of patients’ seizure counts reduced at least 50% and 14 patients were seizure-free for at least 6 months in 2 years, has classified as a Class I Recall at May 2013. The model animal in this experiment is Long-Evans rats with absence seizure. We observed the long term effects of applying the deep-brain stimulation with close-loop controller. We carefully recorded the EEG signal during the whole experiment, measured weight weekly, studied the spike-wave-discharge (SWD) form EEG records, impedance of the brain tissue and tissue slice then calculated several indices to describe the phenomenon we discovered. 10 subjects’ seizure lasting time and seizure occurrence had both decreased. After 2 months seizure control, both seizure occurrence and seizure lasting time further decreased compare to the decrease after two weeks seizure control. And we found that electrical stimulation changes structure of brain tissue, including impedance and neurogial cell volume increased, Although the tissue hyperplasia result in electrode covered, our system still can suppress the seizure.

    摘要 I Abstract III List of Figures IX List of Tables VIII Chapter 1 Introduction 1 1.1 Motivation 1 1.2 Seizure Type 2 1.3 Stimulation – suppression for Epilepsy 4 1.4 Seizure Monitoring and Controlling System 5 1.5 Bioelectrical Impedance 6 1.6 Relative Works 8 1.6.1 Medtronic 8 1.6.2 RNS system 9 1.7 Study Objective 11 1.8 Thesis Organization 11 Chapter 2 Method 12 2.1 Animal Subjects and Surgery 12 2.2 Stimulation of Zona Incerta 12 2.3 Real-time Close-loop Seizure Monitor and Control System 15 2.4 Experimental Design 19 2.4.1 Pre-Evaluation 20 2.4.2 Long-Term Monitor/Control Recording 21 2.4.3 Daily record time 22 2.5 Data Pre-Processing 24 2.6 Analysis 24 2.7 Statistical Analysis 27 Chapter 3 Result 28 3.1 Weight 28 3.2 Duration Analysis 29 3.3 Frequency of Seizure Analysis 31 3.4 Waveform of Epilepsy Analysis 32 3.5 Long-term follow-up 34 3.6 Equivalent circuit parameters of impedance 37 Chapter 4 Discussion 43 Impedance and Efficiency of Seizure Suppression 46 Long-tern Seizure Control 48 Chapter 5 Future works 49 Reference 50

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