Longitudinal imaging in C9orf72 mutation carriers: Relationship to phenotype.
Longitudinal imaging in C9orf72 mutation carriers: Relationship to phenotype.
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DOI：
10.1016/j.nicl.2016.10.014
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发表时间：
2016
影响因子：
4.2
通讯作者：
Kwan, Justin Y.
中科院分区：
文献类型：
--
作者：
Floeter, Mary Kay;Bageac, Devin;Danielian, Laura E.;Braun, Laura E.;Traynor, Bryan J.;Kwan, Justin Y.
关键词：
C9 orf 72基因的扩增突变可能导致肌萎缩侧索硬化症（ALS）、额颞叶痴呆（FTD）或两种临床表型的混合。与具有相同表型的散发患者相比，C9 orf 72相关疾病的不同成像结果已被描述，但不确定不同表型是否具有共同的基因型相关成像特征。为了解决这一问题，27名具有不同表型的无关C9 orf 72扩增突变携带者（C9 +）、28名年龄匹配的健康对照和22名散发性ALS（sALS）患者进行了3 T MRI扫描和临床表型分析。从T1图像中提取脑体积和皮质厚度的测量值。与健康对照组和sALS患者相比，有症状的C9 +受试者随年龄增长有更大的心室容积损失和丘脑萎缩，伴有弥漫性、斑片状皮质变薄。无症状携带者与对照组无差异。C9 + ALS和ALS-FTD患者的运动皮质比sALS患者薄，但运动外区域更薄，特别是额叶和颞叶。C9 + ALS患者的上级额回和外侧眶额皮质厚度与散发性ALS患者不同。中央前回的厚度与修订的ALS功能评定量表呈弱相关。许多皮质区域的厚度，包括几个额叶和颞叶区域，与字母流畅性分数中度相关。字母流畅性分数与心室和丘脑体积弱相关。为了更好地了解成像结果与疾病进展的关系，大约6个月后对19名C9 +受试者和23名健康对照进行了扫描。具有FTD和ALS-FTD表型的C9 +患者的心室容积增加，无症状C9 +受试者的心室容积保持稳定。我们的结论是，弥漫性萎缩是一种常见的潜在特征的疾病与C9 orf 72突变在其临床表型。心室扩大可以在6个月的时间范围内测量，并且在认知障碍患者中似乎更快。斑片状皮质变薄和弥漫性萎缩是症状性ALS和FTD C9 orf 72突变携带者的标志。症状性C9 orf 72携带者比散发性ALS患者和健康对照者有更多的萎缩和弥漫性变薄。在有症状的C9 orf 72携带者中，可以在6个月内检测到心室扩大。字母流畅性受损与弥漫性皮质变薄有关。字母流畅性的变化，而不是ALSFRS-R与6个月的心室扩大相关。
Expansion mutations in the C9orf72 gene may cause amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), or mixtures of the two clinical phenotypes. Different imaging findings have been described for C9orf72-associated diseases in comparison with sporadic patients with the same phenotypes, but it is uncertain whether different phenotypes have a common genotype-associated imaging signature. To address this question, 27 unrelated C9orf72 expansion mutation carriers (C9 +) with varied phenotypes, 28 age-matched healthy controls and 22 patients with sporadic ALS (sALS) underwent 3T MRI scanning and clinical phenotyping. Measures of brain volumes and cortical thickness were extracted from T1 images. Compared to healthy controls and sALS patients, symptomatic C9 + subjects had greater ventricular volume loss and thalamic atrophy for age, with diffuse, patchy cortical thinning. Asymptomatic carriers did not differ from controls. C9 + ALS and ALS-FTD patients had less thinning of the motor cortex than sALS patients, but more thinning in extramotor regions, particularly in frontal and temporal lobes. C9 + ALS patients differed from sporadic ALS patients in the thickness of the superior frontal gyrus and lateral orbitofrontal cortex. Thickness of the precentral gyrus was weakly correlated with the revised ALS functional rating scale. Thickness of many cortical regions, including several frontal and temporal regions, was moderately correlated with letter fluency scores. Letter fluency scores were weakly correlated with ventricular and thalamic volume. To better understand how imaging findings are related to disease progression, nineteen C9 + subjects and 23 healthy controls were scanned approximately 6 months later. Ventricular volume increased in C9 + patients with FTD and ALS-FTD phenotypes and remained stable in asymptomatic C9 + subjects. We conclude that diffuse atrophy is a common underlying feature of disease associated with C9orf72 mutations across its clinical phenotypes. Ventricular enlargement can be measured over a 6-month time frame, and appears to be faster in patients with cognitive impairment. Patchy cortical thinning and diffuse atrophy are a hallmark of symptomatic ALS and FTD C9orf72 mutation carriers. Symptomatic C9orf72 carriers have more atrophy and diffuse thinning than sporadic ALS patients and healthy controls. Ventricular enlargement can be detected over a 6-month interval in symptomatic C9orf72 carriers. Impaired letter fluency is associated with diffuse cortical thinning. Changes in letter fluency, but not ALSFRS-R are correlated with 6-month ventricular enlargement.
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