PDF(Pubmed)
Abstract：
OBJECTIVE: Grey matter (GM) atrophy due to neuronal loss is a striking feature of patients with CLN3 disease. A precise and quantitative description of disease progression is needed in order to establish an evaluation tool for current and future experimental treatments. In order to develop a quantitative marker to measure brain volume outcome, we analysed the longitudinal volumetric development of GM, white matter (WM) and lateral ventricles and correlated those with the clinical course.
METHODS: One hundred twenty-two MRI scans of 35 patients (21 females; 14 males; age 15.3 ± 4.8 years) with genetically confirmed CLN3 disease were performed. A three-dimensional T1-weighted sequence was acquired with whole brain coverage. Volumetric segmentation of the brain was performed with the FreeSurfer image analysis suite. The clinical severity was assessed by the Hamburg jNCL score, a disease-specific scoring system.
RESULTS: The volumes of supratentorial cortical GM and supratentorial WM, cerebellar GM, basal ganglia/thalamus and hippocampus significantly (r = - 0.86 to - 0.69, p < 0.0001) decreased with age, while the lateral ventricle volume increased (r = 0.68, p < 0.0001). Supratentorial WM volume correlated poorer with age (r = - 0.56, p = 0.0001). Supratentorial cortical GM volume showed the steepest (4.6% (± 0.2%)) and most uniform decrease with strongest correlation with age (r = - 0.86, p < 0.0001). In addition, a strong correlation with disease specific clinical scoring existed for the supratentorial cortical GM volume (r = 0.85, p = < 0.0001).
CONCLUSIONS: Supratentorial cortical GM volume is a sensitive parameter for assessment of disease progression even in early and late disease stages and represents a potential reliable outcome measure for evaluation of experimental therapies.
METHODS: One hundred twenty-two MRI scans of 35 patients (21 females; 14 males; age 15.3 ± 4.8 years) with genetically confirmed CLN3 disease were performed. A three-dimensional T1-weighted sequence was acquired with whole brain coverage. Volumetric segmentation of the brain was performed with the FreeSurfer image analysis suite. The clinical severity was assessed by the Hamburg jNCL score, a disease-specific scoring system.
RESULTS: The volumes of supratentorial cortical GM and supratentorial WM, cerebellar GM, basal ganglia/thalamus and hippocampus significantly (r = - 0.86 to - 0.69, p < 0.0001) decreased with age, while the lateral ventricle volume increased (r = 0.68, p < 0.0001). Supratentorial WM volume correlated poorer with age (r = - 0.56, p = 0.0001). Supratentorial cortical GM volume showed the steepest (4.6% (± 0.2%)) and most uniform decrease with strongest correlation with age (r = - 0.86, p < 0.0001). In addition, a strong correlation with disease specific clinical scoring existed for the supratentorial cortical GM volume (r = 0.85, p = < 0.0001).
CONCLUSIONS: Supratentorial cortical GM volume is a sensitive parameter for assessment of disease progression even in early and late disease stages and represents a potential reliable outcome measure for evaluation of experimental therapies.
摘要：
目的：由于神经元丢失引起的灰质（GM）萎缩是CLN3病患者的一个显著特点。为了建立用于当前和未来实验治疗的评估工具，需要对疾病进展进行精确和定量的描述。为了开发一种定量标记来测量脑容量结果，我们分析了GM的纵向体积发展，白质（WM）和侧脑室，并与临床病程相关。
方法：对35例（21名女性；14名男性；年龄15.3±4.8岁）的经遗传证实的CLN3疾病患者进行了122次MRI扫描。获得了全脑覆盖的三维T1加权序列。使用FreeSurfer图像分析套件进行大脑的体积分割。通过汉堡jNCL评分评估临床严重程度，疾病特异性评分系统。
结果：幕上皮质GM和幕上WM的体积，小脑GM,随着年龄的增长，基底神经节/丘脑和海马明显减少（r=-0.86至-0.69，p<0.0001），侧脑室容积增加(r=0.68,p<0.0001)。幕上WM体积与年龄的相关性较差（r=-0.56，p=0.0001）。幕上皮质GM体积显示最陡（4.6％（±0.2％））和最均匀的减少，与年龄的相关性最强（r=-0.86，p<0.0001）。此外,幕上皮质GM体积与疾病特异性临床评分存在强相关性(r=0.85,p=<0.0001).
结论：幕上皮质GM体积是评估疾病进展的敏感参数，即使在疾病早期和晚期，也是评估实验治疗的潜在可靠结果指标。
方法：对35例（21名女性；14名男性；年龄15.3±4.8岁）的经遗传证实的CLN3疾病患者进行了122次MRI扫描。获得了全脑覆盖的三维T1加权序列。使用FreeSurfer图像分析套件进行大脑的体积分割。通过汉堡jNCL评分评估临床严重程度，疾病特异性评分系统。
结果：幕上皮质GM和幕上WM的体积，小脑GM,随着年龄的增长，基底神经节/丘脑和海马明显减少（r=-0.86至-0.69，p<0.0001），侧脑室容积增加(r=0.68,p<0.0001)。幕上WM体积与年龄的相关性较差（r=-0.56，p=0.0001）。幕上皮质GM体积显示最陡（4.6％（±0.2％））和最均匀的减少，与年龄的相关性最强（r=-0.86，p<0.0001）。此外,幕上皮质GM体积与疾病特异性临床评分存在强相关性(r=0.85,p=<0.0001).
结论：幕上皮质GM体积是评估疾病进展的敏感参数，即使在疾病早期和晚期，也是评估实验治疗的潜在可靠结果指标。
