Agosta Federica, Ferraro Pilar M, Riva Nilo, Spinelli Edoardo Gioele, Domi Teuta, Carrera Paola, Copetti Massimiliano, Falzone Yuri, Ferrari Maurizio, Lunetta Christian, Comi Giancarlo, Falini Andrea, Quattrini Angelo, Filippi Massimo
Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
Department of Neurology, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy; Neuropathology Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
Neurobiol Aging. 2017 Sep;57:206-219. doi: 10.1016/j.neurobiolaging.2017.05.024. Epub 2017 Jun 6.
This study investigated structural and functional magnetic resonance imaging abnormalities in hexanucleotide repeat expansion in chromosome 9 open reading frame 72 (C9orf72) motor neuron disease (MND) relative to disease severity-matched sporadic MND cases. We enrolled 19 C9orf72 and 67 disease severity-matched sporadic MND patients, and 22 controls. Sporadic cases were grouped in patients with: no cognitive/behavioral deficits (sporadic-motor); same patterns of cognitive/behavioral impairment as C9orf72 cases (sporadic-cognitive); shorter disease duration versus other sporadic groups (sporadic-early). C9orf72 patients showed cerebellar and thalamic atrophy versus all sporadic cases. All MND patients showed motor, frontal, and temporoparietal cortical thinning and motor and extramotor white matter damage versus controls, independent of genotype and presence of cognitive impairment. Compared with sporadic-early, C9orf72 patients revealed an occipital cortical thinning. C9orf72 patients had enhanced visual network functional connectivity versus sporadic-motor and sporadic-early cases. Structural cerebellar and thalamic damage and posterior cortical alterations are the brain magnetic resonance imaging signatures of C9orf72 MND. Frontotemporal cortical and widespread white matter involvement are likely to be an effect of the disease evolution rather than a C9orf72 marker.
本研究调查了9号染色体开放阅读框72（C9orf72）运动神经元病（MND）中六核苷酸重复扩增相关的结构和功能磁共振成像异常，与疾病严重程度匹配的散发性MND病例进行对比。我们纳入了19例C9orf72患者和67例疾病严重程度匹配的散发性MND患者，以及22名对照者。散发性病例分为以下几组：无认知/行为缺陷（散发性运动型）；与C9orf72病例具有相同认知/行为损害模式（散发性认知型）；病程短于其他散发性组（散发性早期）。与所有散发性病例相比，C9orf72患者表现出小脑和丘脑萎缩。与对照组相比，所有MND患者均表现出运动、额叶和颞顶叶皮质变薄以及运动和运动外白质损伤，与基因型和认知障碍的存在无关。与散发性早期患者相比，C9orf72患者表现出枕叶皮质变薄。与散发性运动型和散发性早期病例相比，C9orf72患者视觉网络功能连接增强。小脑和丘脑的结构性损伤以及后皮质改变是C9orf72 MND的脑磁共振成像特征。额颞叶皮质和广泛的白质受累可能是疾病进展的结果，而非C9orf72的标志物。
