Manners D N, Rizzo G, La Morgia C, Tonon C, Testa C, Barboni P, Malucelli E, Valentino M L, Caporali L, Strobbe D, Carelli V, Lodi R
From the Functional MR Unit (D.N.M., G.R., C.Tonon, C.Testa, R.L.).
From the Functional MR Unit (D.N.M., G.R., C.Tonon, C.Testa, R.L.) Neurology Unit (G.R., C.L.M., M.L.V., L.C., D.S., V.C.), Department of Biomedical and NeuroMotor Sciences.
AJNR Am J Neuroradiol. 2015 Jul;36(7):1259-65. doi: 10.3174/ajnr.A4272. Epub 2015 Mar 19.
Brain white matter is frequently affected in mitochondrial diseases; optic atrophy gene 1-autosomal dominant optic atrophy and Leber hereditary optic neuropathy are the most frequent mitochondrial monosymptomatic optic neuropathies. In this observational study, brain white matter microstructure was characterized by DTI in patients with optic atrophy gene 1-autosomal dominant optic atrophy and Leber hereditary optic neuropathy, in relation to clinical and genetic features.
Nineteen patients with optic atrophy gene 1-autosomal dominant optic atrophy and 17 with Leber hereditary optic neuropathy older than 18 years of age, all genetically diagnosed, and 19 healthy volunteers underwent DTI by using a 1.5T MR imaging scanner and neurologic and ophthalmologic assessments. Brain white matter DTI metrics were calculated for all participants, and, in patients, their correlations with genetics and clinical findings were calculated.
Compared with controls, patients with optic atrophy gene 1-autosomal dominant optic atrophy had an increased mean diffusivity in 29.2% of voxels analyzed within major white matter tracts distributed throughout the brain, while fractional anisotropy was reduced in 30.3% of voxels. For patients with Leber hereditary optic neuropathy, the proportion of altered voxels was only 0.5% and 5.5%, respectively, of which half was found within the optic radiation and 3.5%, in the smaller acoustic radiation. In almost all regions, fractional anisotropy diminished with age in patients with optic atrophy gene 1-autosomal dominant optic atrophy and correlated with average retinal nerve fiber layer thickness in several areas. Mean diffusivity increased in those with a missense mutation. Patients with Leber hereditary optic neuropathy taking idebenone had slightly milder changes.
Patients with Leber hereditary optic neuropathy had preferential involvement of the optic and acoustic radiations, consistent with trans-synaptic degeneration, whereas patients with optic atrophy gene 1-autosomal dominant optic atrophy presented with widespread involvement suggestive of a multisystemic, possibly a congenital/developmental, disorder. White matter changes in Leber hereditary optic neuropathy and optic atrophy gene 1-autosomal dominant optic atrophy may be exploitable as biomarkers.
脑白质在线粒体疾病中常受影响；视神经萎缩基因1 - 常染色体显性遗传性视神经萎缩和Leber遗传性视神经病变是最常见的线粒体单症状性视神经病变。在这项观察性研究中，利用弥散张量成像（DTI）对患有视神经萎缩基因1 - 常染色体显性遗传性视神经萎缩和Leber遗传性视神经病变患者的脑白质微观结构进行特征描述，并分析其与临床及基因特征的关系。
19例年龄大于18岁的视神经萎缩基因1 - 常染色体显性遗传性视神经萎缩患者和17例Leber遗传性视神经病变患者，均经基因诊断，以及19名健康志愿者接受了1.5T磁共振成像扫描仪的DTI检查及神经学和眼科评估。计算所有参与者的脑白质DTI指标，并在患者中计算其与遗传学及临床发现的相关性。
与对照组相比，视神经萎缩基因1 - 常染色体显性遗传性视神经萎缩患者在全脑主要白质束内分析的29.2%的体素中平均扩散率增加，而在30.3%的体素中各向异性分数降低。对于Leber遗传性视神经病变患者，改变的体素比例分别仅为0.5%和5.5%，其中一半位于视辐射内，3.5%位于较小的听辐射内。在几乎所有区域，视神经萎缩基因1 - 常染色体显性遗传性视神经萎缩患者的各向异性分数随年龄降低，且在几个区域与平均视网膜神经纤维层厚度相关。错义突变患者的平均扩散率增加。服用艾地苯醌的Leber遗传性视神经病变患者变化稍轻。
Leber遗传性视神经病变患者优先累及视辐射和听辐射，符合跨突触变性，而视神经萎缩基因1 - 常染色体显性遗传性视神经萎缩患者表现为广泛受累，提示多系统疾病，可能是先天性/发育性疾病。Leber遗传性视神经病变和视神经萎缩基因1 - 常染色体显性遗传性视神经萎缩中的白质变化可能可作为生物标志物。
