散发型而非纯合子D90A SOD1 ALS患者皮质兴奋性异常  

Abnormal cortical excitability in sporadic but not homozygous D90A SOD1 ALS

作　　者：Turner M.R. Osei-Lah A.D. Hammers A. 黄媛 

机构地区：[1]Dr. ANC, Institute of Psychiatry, De Crespigny Park, London SE58AF, United Kingdom

出　　处：《世界核心医学期刊文摘（神经病学分册）》2005年第12期49-49,共1页Digest of the World Core Medical Journals:Clinical Neurology

摘　　要：Background: Excitotoxicity is one pathogenic mechanism proposed in amyotrophic lateral sclerosis (ALS), and loss of cortical inhibitory influence may be contributory. Patients with ALS who are homozygous for the D90A superoxide dismutase-1 (SOD1) gene mutation (homD90A) have a unique phenotype, associated with prolonged survival compared with patients with sporadic ALS (sALS). In this study, transcranial magnetic stimulation (TMS) was used to explore cortical excitation and inhibition. Flumazenil binds to the benzodiazepine subunit of the GABAA receptor, and 11C-flumazenil positron emission tomography (PET) was used as a marker of cortical neuronal loss and/or dysfunction, which might in turn reflect changes in cortical inhibitory GABAergic mechanisms. Methods: Cortical responses to single and paired stimulus TMS were compared in 28 patients with sALS and 11 homD90A patients versus 24 controls. TMS measures included resting motor threshold, central motor conduction time, silent period, intracortical inhibition (ICI), and facilitation. 11C-flumazenil PET of the brain was performed on 20 patients with sALS and nine with homD90A. Statistical parametric mapping was used to directly compare PET images from the two patient groups to identify those areas of relatively reduced cortical 11C-flumazenil binding that might explain differences in cortical excitability seen using TMS. Results: Increased cortical excitability, demonstrated by reduction in ICI, was seen in the patients with sALS but not the homD90A patients. A relative reduction in cortical 11C-flumazenil binding was found in the motor and motor association regions of the superior parietal cortices of the patients with sALS. Conclusions: A cortical inhibitory deficit in sALS was not demonstrable in a homogeneous genetic ALS population of similar disability, suggesting a distinct cortical vulnerability. 11C-flumazenil PET demonstrated that neuronal loss/dysfunction in motor and motor association areas may underlie this difference. The corollary, that there may beBackground: Excitotoxicity is one pathogenic mechanism proposed in amyotrophic lateral sclerosis (ALS), and loss of cortical inhibitory influence may be contributory. Patients with ALS who are homozygous for the D90A superoxide dismutase-1 (SOD1) gene mutation (homD90A) have a unique phenotype, associated with prolonged survival compared with patients with sporadic ALS (sALS). In this study, transcranial magnetic stimulation (TMS) was used to explore cortical excitation and inhibition. Flumazenil binds to the benzodiazepine subunit of the GABAA receptor, and 11C-flumazenil positron emission tomography (PET) was used as a marker of cortical neuronal loss and/or dysfunction, which might in turn reflect changes in cortical inhibitory GABAergic mechanisms. Methods: Cortical responses to single and paired stimulus TMS were compared in 28 patients with sALS and 11 homD90A patients versus 24 controls. TMS measures included resting motor threshold, central motor conduction time, silent period, intracortical inhibition (ICI), and facilitation. 11C-flumazenil PET of the brain was performed on 20 patients with sALS and nine with homD90A. Statistical parametric mapping was used to directly compare PET images from the two patient groups to identify those areas of relatively reduced cortical 11C-flumazenil binding that might explain differences in cortical excitability seen using TMS. Results: Increased cortical excitability, demonstrated by reduction in ICI, was seen in the patients with sALS but not the homD90A patients. A relative reduction in cortical 11C-flumazenil binding was found in the motor and motor association regions of the superior parietal cortices of the patients with sALS. Conclusions: A cortical inhibitory deficit in sALS was not demonstrable in a homogeneous genetic ALS population of similar disability, suggesting a distinct cortical vulnerability. 11C-flumazenil PET demonstrated that neuronal loss/dysfunction in motor and motor association areas may underlie this difference. The corollary, that there may be

关 键 词：散发型 纯合子 氟马西尼 经颅磁刺激 性异常 成对刺激 运动阈值 存活时间 基因突变 同型 

分 类 号：R744[医药卫生—神经病学与精神病学]