Functional Studies in Adrenomyeloneuropathy

肾上腺脑白质营养不良是一种遗传性疾病，其由过氧化物酶体β氧化缺陷引起，由于位于Xq28的基因ABCD 1的突变导致饱和极长链脂肪酸（VLCFA）的积累。它主要影响神经系统、肾上腺皮质和睾丸间质细胞。表型变异性很高，不同的儿童形式的疾病和成人形式，肾上腺脊髓神经病（ALVIN）占所有病例的80%。在受影响的男性中，AMN最常见于20多岁晚期，表现为痉挛性下肢轻瘫，在数十年内进行性发展，通常在40或50岁时导致严重残疾。大约一半的女性为酒精性痴呆杂合子 在以后的几年里发展成AMN样脊髓病。AMN主要累及脊髓，神经病理学研究显示远端轴突病变，最严重的累及颈区的上行背柱和下行皮质脊髓束。 AMN的治疗评价受到其进展速度缓慢和目前可用的工具缺乏敏感性来评估参与程度的阻碍。根据目前的临床技术，需要五年或更长时间来评估治疗效果。使用最近开发和实施的研究，初步数据表明，这些将允许及时准确评估疾病进展。这些技术是：1）由Amy Bastian博士在Kennedy Krieger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）：FM中开发的颈脊髓束的磁化传递轮廓成像技术 柯比研究中心本研究拟在基线、6个月和1年时检查30例继发于ALD的早期成人疾病患者的功能和成像技术，以确定感觉和运动功能的具体进展，并将这些发现与颈脊髓背柱和皮质脊髓侧束成像相关联。

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.