於全麻狀態下巴金森暨其他動作障礙疾病之基底核電生理研究

Abstract

對於無法忍受清醒深部腦刺激手術的巴金森及動作障礙患者，於全麻狀態下進行手術是一種選擇。然而我們並不瞭解麻醉劑對視丘下核(subthalamic nucleus)及蒼白球內側(internal globus pallidus)的深部腦刺激手術術中微電位記錄(microelectrode recording)的作用及影響。如果能夠了解麻醉劑對於這些腦區神經元活動的作用及影響，將使我們於全麻狀態下進行的深部腦刺激手術定位及相關核區辨認有莫大助益。於此論文中，我們會有三個主題探討: 第一是有關於desflurane 氣體麻醉劑對於視丘下核微電位紀錄的探討。我們回溯性的選取於連續19位巴金森患者於花蓮慈濟醫院接受雙側視丘下核深部腦刺激手術。其中有10位接受desflurane氣體麻醉，另外9位接受局部麻醉於清醒狀態下手術。我們分析比較兩組(全麻和局麻)術中微電位記錄，使用了傳統的單一神經元放電分析(spike analysis)，Hilbert transform神經訊號能量分析，另外加上結合自相關及頻譜分析以了解神經元放電型態及震盪波動。我們的分析結果顯示兩組其叢發指標(burst index)兩組相似，代表兩組神經元放電皆維持相似程度的振發特性。神經訊號能量分析顯示，於全麻狀態下視丘下核神經元放電能量明顯降低，顯示麻醉劑對神經元放電有抑制效果。自相關的頻譜分析則發現麻醉劑讓視丘下核神經元放電於4-8Hz震盪波動大幅增加。基於以上的分析及結果，我們可以做出以下結論 : desflurane麻醉劑讓巴金森病患視丘下核神經元能量訊號減弱但是其叢發特性沒有改變。於全麻下，視丘下核神經元放電低頻(4-8Hz)震盪的增強，可以視為desflurane對視丘下核神經元的影響特徵。第二是關於在desflurane全身麻醉下，探討巴金森及肌張力不全病患的蒼白球內側術中微電位紀錄表現。我們發現1)巴金森病患的蒼白球(內側及外側)神經元放電頻率高於肌張力不全患者。2)蒼白球外側放電頻率皆低於蒼白球內側。3)明顯神經元低頻震盪特性可見於這兩類病患的蒼白球內側及巴金森病患的蒼白球外側。經由這些蒼白球術中微電位紀錄特性，我們可以在全麻的狀況下，經由術中微電位紀錄，精準的定位，成功完成蒼白球內側深部腦刺激手術。第三是探討非典型巴金森病患(多系統退化症)其視丘下核術中微電位紀錄表現。雖然病患及神經元紀錄不多，我們仍可以明顯看出其視丘下核放電頻率很小(10Hz)且有明顯低頻震盪特性。這些發現可以顯示多系統退化症其神經退化較為廣泛，可能包含視丘下核本身。因此視丘下核深部腦刺激手術對於多系統退化症之效果不佳。總結而言，在全麻狀況下，視丘下核及蒼白球內側術中微電位紀錄是可行且具有定位價值。除了刺激電極置放的準確性外，篩選出合適之病患(如巴金森氏症及肌張力不全症)也是深部腦刺激手術治療的成功關鍵。

Patients with Parkinson’s disease (PD) or other movement disorders who are unable to tolerate awake deep brain stimulation (DBS) surgery, operation under general anesthesia (GA) is the only choice. The effect of anesthetics on intraoperative microelectrode recording (MER) remains controversial. Understanding the effect of anesthetics on MER is important in performing DBS surgery with GA. In the dissertation, three topics will be explored to understand the change of intraoperative MER in GA. First, we retrospectively performed qualitative and quantitative analysis of subthalamic nucleus (STN) MER in GA and local anesthesia (LA). 19 consecutive PD patients who received bilateral STN DBS surgery in Hualien Tzu-Chi hospital under either desflurane GA (n=10) or LA (n=9). We used spike sorting to perform frequency and modified burst index [MBI], STN firing pattern characteristics were determined using a combined approach based on the autocorrelograms and power spectral analysis, which was employed to investigate differences in the oscillatory activities between the groups. Additionally, the Hilbert transform to obtain signal power measurements for background and spikes. The results revealed burst firing was observed in both groups. The firing frequencies were greater in the LA group and MBI was comparable in both groups. Both the background and spikes were of significantly greater power in the LA group. The power spectra of the autocorrelograms were significantly higher in the GA group between 4 and 8 Hz. Under controlled light desflurane GA, burst features of the neuronal firing patterns are preserved in the STN, but power is reduced. Enhanced low-frequency (4-8 Hz) oscillations in the MERs for the GA group could be a characteristic signature of desflurane’s effect on neurons in the STN. Second, intraoperative MER of internal and external globus pallidus (GPi and GPe) in PD and dystonia patients under desflurane anesthesia had been investigated. The results showed 1) the firing frequency of GPi and GPe in PD patients was higher than dystonia patients. 2) The firing rate of GPe neurons was lower than GPi neurons in PD and dystonia patients. 3) prominent low frequency oscillation had been observed in GPi of both patients and GPe in PD patients. The three marks of MER in globus pallidus will ensure the MER accurate location during DBS surgery in PD and dystonia patients. Third, few MERs of multiple system atrophy (MSA) had been analysed. Slow firing rate (10 Hz) and prominent low frequency oscillation were noted. This results may suggest wider degeneration of MSA including STN compared PD and dystonia. In conclusion, intraoperative MER is feasible and provides useful localization information in controlled desflurane anesthesia. Patient selection with suitable diseases (PD and dystonia but not MSA) is another key step to perform successful DBS operation.