利用磁振造影探討左右亞型內側顳葉癲癇患者巴貝茲迴路之退化並其與記憶功能之相關性

Abstract

內側顳葉癲癇併發內側顳葉硬化症（mesial temporal lobe epilepsy with mesial temporal sclerosis, MTLE-MTS）是一種常見的癲癇疾病，其特徵是由邊緣系統引起的癲癇發作。巴貝茲迴路(Papez circuit)是負責記憶和情感的神經迴路，也是邊緣系統的主要途徑之一。左側患側和右側患側MTLE-MTS在白質和灰質中表現出不同模式的大腦結構改變。神經心理學研究報告指出，左、右患側的MTLE-MTS在記憶，情感和執行功能方面表現出不同的大腦功能障礙。在這項研究中，我們旨在調查左、右患側MTLE-MTS中巴貝茲迴路的腦部退化模式，以及它們與記憶功能和臨床特徵因子之間的關聯性。我們招募了18位左側MTLE-MTS患者、17位右側MTLE-MTS患者和37位年齡匹配的對照組，所有受試者皆使用同一台3T磁振造影系統掃描獲得T1加權影像以及擴散頻譜影像(diffusion spectrum imaging, DSI)。神經心理測驗由專門設計的任務構成，這些任務用於測量已知與特定大腦結構或途徑有關的心理功能。我們使用標準模型（normative model）對白質纖維束之變化和灰質體積之萎縮進行量化，該模型透過將擴散指數與年齡、性別匹配的人群進行比較，將擴散指數轉換為Z分數。研究結果表明，相對於左側患側MTLE-MTS和對照組，右側患側MTLE-MTS在白質完整性和灰質體積方面表現出更顯著的改變，顯示右側患側MTLE-MTS的脫髓鞘作用和軸突損傷更為嚴重。此外，MTLE患者也有認知功能障礙的情形。左側患側MTLE-MTS的影響傾向於跟言語記憶障礙有關的神經束，右側患側MTLE-MTS的影響傾向於跟視覺記憶障礙有關的神經束。另外，左、右患側MTLE-MTS患者在白質特徵方面，分別與發病年齡、病程長度存在顯著但相反的相關性，從而提供了MTLE-MTS左右亞型中白質性質與臨床特徵因子之關聯性。總之，此研究揭示了巴貝茲迴路中大腦退化的雙側特異性，並揭示了MTLE-MTS左右亞型之間神經病理學和臨床表現的不同，希望對於臨床診斷有其貢獻和助益。

Mesial temporal lobe epilepsy with mesial temporal sclerosis (MTLE-MTS) is a common type of epilepsy characterized by seizures arising from the limbic system. The Papez circuit is a neural circuit representing one of the anatomic substrates of memory and emotion, which is one of the major pathways in the limbic system. It has been reported that MTLE-MTS at left lesion and that with right lesion behave distinct patterns of alteration of brain structures in both white matter and gray matter. Neuropsychological studies have reported that left MTLE-MTS and right MTLE-MTS present different dysfunctions in memory, emotion and executive functioning. In this study, we aimed to investigate the degeneration patterns of the Papez circuit in left MTLE-MTS and right MTLE-MTS, and their associations with memory functions and clinical factors. We recruited 18 left MTLE-MTS and 17 right MTLE-MTS patients, and 37 age-matched controls. All participants received T1-weighted imaging and diffusion spectrum imaging on the same 3T MRI scanner. Neuropsychological test constitutes specifically designed tasks used to measure a psychological function known to be linked to a particular brain structure or pathway. We quantified white matter fiber tract alterations gray matter volume atrophy using a normative model which transformed the diffusion indices into the z-scores by comparing them to the age- and sex-matched population. The results showed that patients with right MTLE-MTS exhibited more alterations in white matter integrity and gray matter volume than patients with left MTLE-MTS and the controls, suggesting a more aggravated demyelination and axonal injury in right MTLE-MTS. In addition, MTLE-MTS patients also exhibited neuropsychological deterioration. Left MTLE-MTS tended to have affected tracts related to verbal memory disability, and right MTLE-MTS tended to have affected tracts related to visual memory deficits. Moreover, patients with left and right MTLE-MTS revealed significant but opposite correlations of the white matter tract properties with the clinical factors including age of onset and duration of illness, which provide the clinical relevance of white matter properties in two subtypes of MTLE-MTS. In conclusion, our findings reveal the side-specific associations of brain degeneration in the Papez circuit and suggest different neuropathology and clinical manifestations in two subtypes of MTLE-MTS.