Rocca Maria A, Bianchi-Marzoli Stefania, Messina Roberta, Cascavilla Maria Lucia, Zeviani Massimo, Lamperti Costanza, Milesi Jacopo, Carta Arturo, Cammarata Gabriella, Leocani Letizia, Lamantea Eleonora, Bandello Francesco, Comi Giancarlo, Falini Andrea, Filippi Massimo
Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Via Olgettina, 60, 20132, Milan, Italy.
J Neurol. 2015 May;262(5):1216-27. doi: 10.1007/s00415-015-7696-5. Epub 2015 Mar 21.
Using advanced MRI techniques, we investigated the presence and topographical distribution of brain grey matter (GM) and white matter (WM) alterations in dominant optic atrophy (DOA) patients with genetically proven OPA1 mutation as well as their correlation with clinical and neuro-ophthalmologic findings. Nineteen DOA patients underwent neurological, neuro-ophthalmologic and brainstem auditory evoked potentials (BAEP) evaluations. Voxel-wise methods were applied to assess regional GM and WM abnormalities in patients compared to 20 healthy controls. Visual acuity was reduced in 16 patients. Six DOA patients (4 with missense mutations) had an abnormal I peripheral component (auditory nerve) at BAEP. Compared to controls, DOA patients had significant atrophy of the optic nerves (p < 0.0001). Voxel-based morphometry (VBM) analysis showed that, compared to controls, DOA patients had significant WM atrophy of the chiasm and optic tracts; whereas no areas of GM atrophy were found. Tract-based spatial statistics (TBSS) analysis showed that compared to controls, DOA patients had significantly lower mean diffusivity, axial and radial diffusivity in the WM of the cerebellum, brainstem, thalamus, fronto-occipital-temporal lobes, including the cingulum, corpus callosum, corticospinal tract and optic radiation bilaterally. No abnormalities of fractional anisotropy were detected. No correlations were found between volumetric and diffusivity abnormalities quantified with MRI and clinical and neuro-ophthalmologic measures of disease severity. Consistently with pathological studies, tissue loss in DOA patients is limited to anterior optic pathways reflecting retinal ganglion cell degeneration. Distributed abnormalities of diffusivity indexes might reflect abnormal intracellular mitochondrial morphology as well as alteration of protein levels due to OPA1 mutations.
我们运用先进的磁共振成像（MRI）技术，研究了基因检测证实存在OPA1突变的显性遗传性视神经萎缩（DOA）患者脑灰质（GM）和白质（WM）改变的存在情况、地形分布，以及它们与临床和神经眼科检查结果之间的相关性。19例DOA患者接受了神经学、神经眼科和脑干听觉诱发电位（BAEP）评估。采用体素分析方法评估患者与20名健康对照者的脑区GM和WM异常情况。16例患者视力下降。6例DOA患者（4例为错义突变）BAEP检查I波外周成分（听神经）异常。与对照组相比，DOA患者视神经显著萎缩（p < 0.0001）。基于体素的形态学测量（VBM）分析显示，与对照组相比，DOA患者视交叉和视束白质显著萎缩；而未发现脑灰质萎缩区域。基于纤维束的空间统计学（TBSS）分析显示，与对照组相比，DOA患者双侧小脑、脑干、丘脑、额颞枕叶白质（包括扣带束、胼胝体、皮质脊髓束和视辐射）的平均扩散率、轴向扩散率和径向扩散率显著降低。未检测到各向异性分数异常。MRI定量分析的体积和扩散率异常与疾病严重程度的临床和神经眼科指标之间未发现相关性。与病理学研究一致，DOA患者的组织损失仅限于反映视网膜神经节细胞变性的前部视觉通路。扩散率指标的分布异常可能反映了OPA1突变导致的细胞内线粒体形态异常以及蛋白质水平改变。
