Distinct cerebral lesions in sporadic and 'D90A' SOD1 ALS:: studies with [11C]flumazenil PET
Distinct cerebral lesions in sporadic and 'D90A' SOD1 ALS:: studies with [11C]flumazenil PET
复制标题
DOI：
10.1093/brain/awh509
复制
发表时间：
2005-06-01
期刊：
影响因子：
14.5
通讯作者：
Leigh, PN
中科院分区：
文献类型：
--
作者：
Turner, MR;Hammers, A;Leigh, PN
5%到10%的肌萎缩侧索硬化症（ALS）病例与超氧化物歧化酶-1（SOD 1）基因突变有关，“D90 A”突变与独特的表型和明显较慢的疾病进展（平均生存时间14年）有关。抑制性皮层神经元回路的相对保留可能是导致D90 A突变纯合子（homD 90 A）患者进展较慢的一种机制。GABA（A）受体PET配体[C-11]氟马西尼已证实在散发性ALS中存在运动和运动外皮质变化。在这项研究中，我们使用[C-11]氟马西尼PET探索偶发性和遗传同质性ALS组之间皮质受累模式的差异。24名散发性ALS（sALS）和10名homD 90 A患者接受了[C-11]氟马西尼脑PET。此外，2例D90 A突变纯合子，但无症状或体征（“前驱”，psD 90 A）的受试者也接受了成像。每组的结果与24名年龄相仿的健康对照组进行比较。在sALS组中，[C-11]氟马西尼的结合减少见于运动前区、运动皮质和后运动联合区。然而，在ALS患者的homD 90 A组中，下降集中在左侧额颞交界处和前扣带回。在两名psD 90 A受试者中，在左侧额颞交界处观察到[C-11]氟马西尼结合减少的小病灶，与临床受累患者中观察到的模式相似。在sALS组中，皮质[C-11]氟马西尼结合减少与修订的ALS功能评定量表（ALSFRS-R评分）之间无统计学显著相关性，而上运动神经元（UMN）评分与优势半球广泛和显著的皮质减少相关。在homD 90 A组中，皮质[C-11]氟马西尼结合减少与ALSFRS-R评分（而非UMN评分）以及疾病持续时间之间存在更强的统计学相关性。本研究提供了证据，证明homD 90 A与sALS患者相比，皮质[C-11]氟马西尼结合减少的分布存在差异。我们推测这可能反映了皮层神经元脆弱性的差异。
Five to ten percent of amyotrophic lateral sclerosis (ALS) cases are associated with mutations of the superoxide dismutase-1 (SOD1) gene, and the 'D90A' mutation is associated with a unique phenotype and markedly slower disease progression (mean survival time 14 years). Relative sparing of inhibitory cortical neuronal circuits might be one mechanism contributing to the slower progression in patients homozygous for the D90A mutation (homD90A). The GABA(A) receptor PET ligand [C-11]flumazenil has demonstrated motor and extra-motor cortical changes in sporadic ALS. In this study, we used [C-11]flumazenil PET to explore differences in the pattern of cortical involvement between sporadic and genetically homogeneous ALS groups. Twenty-four sporadic ALS (sALS) and 10 homD90A patients underwent [C-11]flumazenil PET of the brain. In addition, two subjects homozygous for the D90A mutation, but without symptoms or signs ('pre-symptomatic', psD90A), also underwent imaging. Results for each group were compared with those for 24 healthy controls of similar age. Decreases in the binding of [C-11]flumazenil in the sALS group were found within premotor regions, motor cortex and posterior motor association areas. In the homD90A group of ALS patients, however, decreases were concentrated in the left fronto-temporal junction and anterior cingulate gyrus. In the two psD90A subjects, a small focus of reduced [C-11]flumazenil binding at the left fronto-temporal junction was seen, similar to the pattern seen in the clinically affected patients. Within the sALS group, there was no statistically significant association between decreases in cortical [C-11]flumazenil binding and revised ALS functional rating scale (ALSFRS-R score), whereas the upper motor neuron (UMN) score correlated with widespread and marked cortical decreases over the dominant hemisphere. In the homD90A group, there was a stronger statistical association between reduced cortical [C-11]flumazenil binding and the ALSFRS-R, rather than the UMN, score, and also with disease duration. This study provides evidence for differences in the distribution of reduced cortical [C-11]flumazenil binding in homD90A compared with sALS patients. We hypothesize that this might reflect differences in cortical neuronal vulnerability.