家族性澱粉樣多發性神經病變自主神經功能障礙的結構連結改變

Abstract

家族性澱粉樣多發性神經病變是一種罕見且致命的遺傳性疾病，由甲狀腺素運載蛋白突變引起，使澱粉樣蛋白沉積在多個器官中而造成多系統疾病，特別是神經系統的損害。自主神經症狀和小纖維神經受損的感覺異常是台灣家族性澱粉樣多發性神經病變患者的早期表現。過去研究大部分是探討臨床症狀與周邊神經機制的關係，但漸漸發現了周邊神經損傷後中樞系統也跟著發生改變。近年來學者使用糖尿病神經病變作為小纖維神經病變模型，發現了病理機制、臨床功能和大腦網路之間的關係，顯示小纖維神經病變並不是純粹的周邊神經系統疾病，而是和中樞神經系統息息相關。因此我們的研究目的是使用機率擴散纖維束成像技術來研究的大腦結構連接變化與臨床症狀的關聯，並在家族性澱粉樣多發性神經病變患者和健康成年人之間的大腦連結性進行組間比較。 研究結果發現心律變異度與腦部造影改變之間存在顯著關聯。大腦導水管周圍灰質與額葉、丘腦、海馬迴、島葉和扣帶回之間的結構性連結和心律變異度呈現正相關，顯示自主神經系統調節越差則導水管周圍灰質結構性連結越低。丘腦與額葉和前扣帶皮層區域之間的結構性連結和 COMPASS31 總分之間呈現負相關，顯示自主神經症狀越多則丘腦結構性連結越低。此外於組間比較中，大腦導水管周圍灰質、杏仁核、下視丘和前島葉結構性連結較低。這些發現暗示大腦結構連接與周圍損傷有關，並可能為我們提供非侵入性生物標記或相關治療的未來候選。

Familial amyloid polyneuropathy (FAP) is a group of uncommon, life-threatening hereditary disease due to mutation of transthyretin, causing deposition of amyloid proteins in various organ systems with multisystem disorders, particularly the nervous system. In Taiwan, FAP patients often exhibit early symptoms of small-fiber sensory neuropathy and autonomic dysfunction. Past studies mostly link clinical symptoms to peripheral mechanism, but maladaptive plasticity in the central nervous system following peripheral nerve injury was been found also. Recently, researchers used diabetic neuropathy as a small fiber neuropathy model and found connections among the pathology, clinical function, and brain network, suggesting that SFN is not a pure peripheral nervous system disorder. Our aim is to use probabilistic diffusion tractography to investigate the brain structural connectivity changes correlated with clinical symptoms and examine group comparisons between patients with FAP and healthy adults. Current results showed that a significant association was found between R-R interval variation (RRIV) and brain imaging alterations. A positive correlation was found between the RRIV and SC between the periaqueductal gray (PAG) with frontal, thalamus, hippocampus, insula, and cingulate, indicating that poorer regulation of the autonomic nervous system (ANS) was associated with decreased PAG SC. Negative correlation was found between the COMPASS 31 sum score and SC between the thalamus with the frontal and anterior cingulate cortex(ACC) region, indicating that poorer subjective symptoms was associated with decreased thalamic SC. Furthermore, lower SC was found in PAG, amygdala, hypothalamus, and anterior insula between groups. These findings suggest that brain structural connectivity was correlated with peripheral injury and might provide us a candidate non-invasive biomarker or related treatment in the future.