Functional Studies in Adrenomyeloneuropathy

肾上腺脊髓神经病的功能研究

• 批准号: 6821994
• 负责人: Gerald V. Raymond
• 金额: $ 18.62万
• 依托单位: HUGO W. MOSER RES INST KENNEDY KRIEGER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-12-01 至 2005-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6821994
• 关键词: adrenoleukodystrophy; balance; brain disorder diagnosis; brain imaging /visualization /scanning; clinical research; functional ability; gait; human subject; longitudinal human study; magnetic resonance imaging; neuroimaging; neuromuscular disorder; pathologic process; sensorimotor system

Adrenoleukodystrophy is a genetic disorder that results from a defect in peroxisomal beta oxidation with the accumulation of saturated very long chain fatty acids (VLCFA) due to mutations in ABCD 1, a gene located at Xq28. It affects primarily the nervous system, adrenal cortex, and the Leydig cells of the testes. The phenotypic variability is high with the disparate childhood form of the disease and an adult form, adrenomyeloneuropathy (ALVIN) accounting for 80% of all cases. In affected men, AMN presents most commonly in the late twenties as a spastic paraparesis that is progressive over decades and often leads to severe disability in the fourth or fifth decades. Approximately half of the women heterozygous for ALD develop an AMN-like myelopathy in later years. AMN involves the spinal cord mainly and neuropathological studies have shown a distal axonopathy that involves most severely the ascending dorsal columns in the cervical regions and the descending corticospinal tracts. The evaluation of the therapy of AMN has been hampered by its slow rate of progression and the lack of sensitivity of currently available instruments to assess the degree of involvement. With current clinical techniques, five or more years are required to assess the effects of therapy. Using recently developed and implemented studies, preliminary data suggest that these will permit accurate assessment of disease progression in a timely fashion. These techniques are: 1) a series of quantitative tests of sensory and motor function conducted by Dr. Amy Bastian in the Motion Analysis laboratory at the Kennedy Krieger Institute, and 2): Magnetization Transfer Profile Imaging techniques of the cervical spinal tracts developed in the FM Kirby Research Center. This study proposes to examine the functional and imaging techniques in 30 patients with early adult disease secondary to ALD at baseline, 6 months, and one year to determine the specific progression in sensory and motor function and correlate those findings with the cervical cord imaging of the dorsal columns and lateral corticospinal tracts.

肾上腺脑白质营养不良是一种遗传性疾病，是由于位于Xq28的ABCD 1基因突变导致的过氧化体β氧化缺陷和饱和超长链脂肪酸(VLCFA)的积累造成的。它主要影响神经系统、肾上腺皮质和睾丸的间质细胞。表型变异性很高，儿童型和成人型不同，肾上腺髓神经病(ALVIN)占所有病例的80%。在受影响的男性中，AMN最常见的表现是在30多岁时表现为痉挛瘫痪，几十年来逐渐发展，往往在第四或五十年导致严重残疾。大约一半的ALD杂合子女性 在晚年发展为AMN样脊髓病。AMN主要累及脊髓，神经病理学研究表明，远端轴索病变最严重累及颈区的上升背柱和皮质脊髓下降束。 AMN的进展速度缓慢，目前现有的评估受累程度的仪器缺乏敏感性，这阻碍了对AMN治疗的评估。以目前的临床技术，评估治疗效果需要五年或更长时间。利用最近开发和实施的研究，初步数据表明，这些研究将使及时准确评估疾病进展成为可能。这些技术是：1)由艾米·巴斯蒂安博士在肯尼迪·克里格研究所的运动分析实验室进行的一系列感觉和运动功能的定量测试，以及2)在FM开发的颈椎束磁化传递剖面成像技术 柯比研究中心。这项研究建议在基线、6个月和1年对30名继发于ALD的早期成人疾病患者进行功能和成像技术检查，以确定感觉和运动功能的具体进展，并将这些发现与背柱和皮质脊髓外侧束的颈髓成像相关联。