Wang Ling, Ding Hao, Chen Bihong T, Fan Ke, Tian Qin, Long Miaomiao, Liang Meng, Shi Dapeng, Yu Chunshui, Qin Wen
Department of Medical Imaging, Henan Provincial People's Hospital, Zhengzhou, China.
Department of Radiology & Tianjin Key Lab of Functional Imaging, Tianjin Medical University General Hospital, Tianjin, China.
Eur J Neurol. 2021 Sep;28(9):2871-2881. doi: 10.1111/ene.14995. Epub 2021 Jul 9.
Leber hereditary optic neuropathy (LHON) is a disease maternally inherited from mitochondria that predominantly impairs the retinal ganglion cells and their axons. To identify whether occult brain white matter (WM) impairment is involved, a voxel-based analysis (VBA) of diffusion metrics was carried out in LHON patients with normal-appearing brain parenchyma.
Fifty-four symptomatic LHON patients (including 22 acute LHON with vision loss for ≤12 months, and 32 chronic LHON) without any visible brain lesions and 36 healthy controls (HCs) were enrolled in this study. VBA was applied to quantify the WM microstructural changes of LHON patients. Finally, the associations of the severity of WM impairment with disease duration and ophthalmologic deficits were assessed.
Compared with the HCs, the average retinal nerve fiber layer (RNFL) thickness was significantly reduced in patients with chronic LHON, whereas it was increased in patients with acute LHON (p < 0.05, corrected). VBA identified significantly decreased fractional anisotropy widely in WM in both the acute and chronic LHON patients, including the left anterior thalamic radiation and superior longitudinal fasciculus, and bilateral corticospinal tract, dentate nuclei, inferior longitudinal fasciculus, forceps major, and optic radiation (OR; p < 0.05, corrected). The integrity of most WM structures (except for the OR) was correlated with neither disease duration nor RNFL thickness (p > 0.05, corrected).
Occult primary impairment of widespread brain WM is present in LHON patients. The coexisting primary and secondary WM impairment may jointly contribute to the pathological process of LHON.
Leber遗传性视神经病变（LHON）是一种由线粒体母系遗传的疾病，主要损害视网膜神经节细胞及其轴突。为了确定是否存在隐匿性脑白质（WM）损伤，对脑实质外观正常的LHON患者进行了基于体素的扩散指标分析（VBA）。
本研究纳入了54例有症状的LHON患者（包括22例视力丧失≤12个月的急性LHON患者和32例慢性LHON患者），这些患者均无任何可见的脑部病变，以及36名健康对照者（HCs）。应用VBA来量化LHON患者的WM微观结构变化。最后，评估WM损伤严重程度与病程及眼科缺陷之间的关联。
与HCs相比，慢性LHON患者的平均视网膜神经纤维层（RNFL）厚度显著降低，而急性LHON患者的RNFL厚度增加（p<0.05，校正后）。VBA发现，急性和慢性LHON患者的WM中广泛存在分数各向异性显著降低的情况，包括左侧丘脑前辐射和上纵束，以及双侧皮质脊髓束、齿状核、下纵束、大脑镰、视辐射（OR；p<0.05，校正后）。大多数WM结构（OR除外）的完整性与病程和RNFL厚度均无相关性（p>0.05，校正后）。
LHON患者存在广泛脑WM的隐匿性原发性损伤。原发性和继发性WM损伤并存可能共同促成LHON的病理过程。
