Spinal abnormalities in neurofibomatosis type 1

1 型神经纤维瘤病的脊柱异常

• 批准号: 7409973
• 负责人: DAVID H. VISKOCHIL
• 金额: $ 27.75万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7409973
• 关键词: Academic Medical Centers; Address; Area; Bone Density; Bone Resorption; British Columbia; Child; Clinical; Clinical Management; Clinical Research; Condition; Defect; Deformity; Developmental Bone Diseases; Disease; Dysplasia; Future; Goals; Hereditary Disease; Incidence; Individual; Magnetic Resonance Imaging; Measures; Meningocele; Muscle; Natural History; Neurofibromatosis 1; Outcome; Outcome Study; Pathogenesis; Pathological Dilatation; Patients; Pediatric Hospitals; Peripheral; Prognostic Factor; Recording of previous events; Recruitment Activity; Rotation; Scallop; Screening procedure; Skeletal system; Spinal; Spinal Canal; Spinal Cord; Testing; Therapeutic Clinical Trial; Thick; Universities; Utah; Vertebral column; Wing; X-Ray Computed Tomography; bone; bone health; cohort; crosslink; improved; indexing; long bone; neurofibroma; prognostic; rib bone structure; scoliosis; spine bone structure; tool; urinary; vertebra body

Neurofibromatosis type 1 (NF1) is a common genetic disorder with a high degree of variability of clinical expression, including skeletal abnormalities in over 1/3 of patients. This disorder is associated with spinal abnormalities, long bone dysplasia, and sphenoid wing dysplasia. These osseous manifestations are unpredictable, and the pathogenesis, natural history, and clinical outcome remain relatively obscure. The spinal abnormalities are varied and include scoliosis (common and dystrophic forms), neurofibromas,dural ectasias, meningoceles, and vertebral defects. The primary objectives of this clinical study are to determine the incidence and clinical history of NF1-related spinal abnormalities in a prepubertal cohort of 120 children with NF1 over 3 years. Secondary objectives are to determine the efficacy of various radiographic screening tools as predictors for dystrophic scoliosis. These goals will be accomplished in 3 specific aims. Aim 1 is to identify associations of spinal cord dural ectasias, spinal neurofibromas,and meningoceles with dysplastic osseous abnormalities and dystrophic scoliosis. Spine radiographs and MRI will be used to test the hypothesis that NF1 patients with certain manifestations are more likely to develop dystrophic scoliosis. Aim 2 is to define the clinical history and short-term outcome of dystrophic scoliosis and spine abnromalities with respect to various radiographic indices. It tests the hypothesis that there are quantitative differences in vertebral scalloping and spinal canal and vertebral body cross-sectional areas when there is an associated additional dystrophic abnormality, and these differences are prognostic indicators for dystrophic scoliosis. Aim 3 is to determine the differences in bone health variables between NF1 patients and individuals without NF1, and between NF1 individuals without dystrophic scoliosis versus NF1 individuals who develop dystrophic scoliosis. Dual energy x-ray absorptiometry (DXA) and peripheral quantitative computerized tomography (pQCT) will be used to test the hypothesis that there-are subtle bone abnormalities of bone mineral density, bone area, bone mass, muscle-to-bone ratios, and cortical thickness in NF1. Urinary Dyridinium cross-links will be measured to detect differences in bone resorption. Spinal abnormalities in NF1 are not well understood, and dystrophic scoliosis is a highly morbid condition. This proposal will identify variables in patients with NF1 as prognostic factors for dystrophic scoliosis to improve clinical management.

1 型神经纤维瘤病 (NF1) 是一种常见的遗传性疾病，临床表现存在高度变异性 表达，包括超过 1/3 患者的骨骼异常。这种疾病与脊柱有关 畸形、长骨发育不良和蝶骨翼发育不良。这些骨质表现是 不可预测，发病机制、自然史和临床结果仍然相对模糊。这 脊柱异常多种多样，包括脊柱侧凸（常见形式和营养不良形式）、神经纤维瘤、硬脑膜 扩张、脑膜膨出和脊椎缺损。这项临床研究的主要目的是确定 120 名青春期前儿童队列中 NF1 相关脊柱异常的发生率和临床病史 患有 NF1 超过 3 年。次要目标是确定各种放射线筛查的有效性 作为营养不良性脊柱侧凸预测因子的工具。这些目标将通过 3 个具体目标来实现。目标 1 是 确定脊髓硬脑膜扩张、脊髓神经纤维瘤和脑膜膨出与发育不良的关联 骨质异常和营养不良性脊柱侧弯。脊柱X光片和MRI将用于测试 假设具有某些表现的 NF1 患者更容易发生营养不良性脊柱侧凸。目的 2 是定义营养不良性脊柱侧弯和脊柱异常的临床病史和短期结果 尊重各种射线照相指数。它检验了以下假设：存在数量差异 椎体扇贝形以及椎管和椎体横截面积，当存在相关时 其他营养不良性异常，这些差异是营养不良性脊柱侧凸的预后指标。 目标 3 是确定 NF1 患者与非 NF1 患者之间骨骼健康变量的差异 NF1，以及没有营养不良性脊柱侧凸的 NF1 个体与患有营养不良性脊柱侧凸的 NF1 个体之间的比较 营养不良性脊柱侧凸。双能 X 射线吸收测定法 (DXA) 和外围定量计算机化 断层扫描 (pQCT) 将用于检验骨骼存在细微骨异常的假设 NF1 中的矿物质密度、骨面积、骨量、肌肉与骨的比率和皮质厚度。泌尿 将测量镝交联以检测骨吸收的差异。 NF1 中的脊柱异常 尚不清楚，营养不良性脊柱侧弯是一种高度病态的疾病。该提案将确定 NF1 患者的变量作为营养不良性脊柱侧凸的预后因素，以改善临床管理。