Limited corticospinal tract involvement in amyotrophic lateral sclerosis subjects with the A4V mutation in the copper/zinc superoxide dismutase gene
Limited corticospinal tract involvement in amyotrophic lateral sclerosis subjects with the A4V mutation in the copper/zinc superoxide dismutase gene
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DOI：
10.1002/ana.410430604
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发表时间：
1998-06-01
影响因子：
11.2
通讯作者：
Brown, RH
中科院分区：
文献类型：
--
作者：
Cudkowicz, ME;McKenna-Yasek, D;Brown, RH
我们检查了11例遗传性肌萎缩侧索硬化症（家族性肌萎缩侧索硬化症，FALS）与最常见的铜/锌超氧化物歧化酶1（SOD 1）突变，密码子4（A4 V）丙氨酸取代缬氨酸。对5名受试者进行了尸检。描述了临床和病理结果，并与9例散发性ALS（SALS）患者进行了比较。在10例FALS A4 V受试者中，没有上运动神经元（UMN）受累的临床证据。所有受试者都有下运动神经元（LMN）体征和至少三条肢体失神经支配的电生理证据。所有SALS受试者均有UMN和LMN受累的体征。病理学研究发现，所有的FALS和SALS受试者的LMNs严重异常。在A4 V SOD 1 FALS受试者中，UMN受累不存在或轻度，在SALS受试者中为重度。在ALS A4 V受试者中，运动神经元以外的系统的病理异常更常见。这一信息表明，目前的ALS诊断标准，需要临床证据的上，下运动神经元参与，应修改;即，诊断应被视为建立时，有证据表明失神经支配在三个或更多的肢体和突变的基因SOD 1，即使没有UMN参与的临床体征。
We examined 11 subjects with inherited amyotrophic lateral sclerosis (familial amyotrophic lateral sclerosis, FALS) associated with the most common copper/zinc superoxide dismutase 1 (SOD1) mutation, an alanine for valine substitution in codon 4 (A4V). Autopsies were performed on 5 subjects. The clinical and pathological findings are described and compared with those of 9 sporadic ALS (SALS) subjects. There was no clinical evidence of upper motor neuron (UMN) involvement in 10 FALS A4V subjects. All subjects had lower motor neuron (LMN) signs and electrophysiological evidence of denervation in at least three limbs. All SALS subjects had signs of both UMN and LMN involvement. Pathological studies found severe abnormalities of LMNs in all FALS and SALS subjects. UMN involvement was either absent or mild in the A4V SOD1 FALS subjects and severe in the SALS subjects. Pathological abnormalities in systems other than the motor neurons were more frequent in the FALS A4V subjects. This information suggests that current diagnostic criteria for ALS, requiring clinical evidence for both upper and lower motor neuron involvement, should be modified; ie, the diagnosis should be deemed established when there is evidence of denervation in three or more limbs and a mutation in the gene for SOD1, even without clinical signs of UMN involvement.