Muscle, Joint and Movement Deterioration Contributing to Neuropathic Forefoot Deformity

肌肉、关节和运动恶化导致神经性前足畸形

• 批准号: 9883786
• 负责人: MARY K HASTINGS
• 金额: $ 20.59万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-01 至 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9883786
• 关键词: Address; Advanced Glycosylation End Products; Amputation; Ankle; Articular Range of Motion; Collagen; Control Groups; Data; Deformity; Deterioration; Development; Diabetes Mellitus; Diabetic Foot; Disease; Distal; Event; Exercise; Extensor; Fluorescence; Foot Deformities; Foot joint structure; Goals; Hyperglycemia; Incidence; Individual; Intervention; Joints; Lead; Leg; Lower Extremity; Magnetic Resonance Imaging; Measurement; Measures; Metatarsal bone structure; Metatarsophalangeal joint structure; Monitor; Motion; Movement; Muscle; Muscular Atrophy; Neuropathy; Participant; Pathway interactions; Pattern; Peripheral Nervous System Diseases; Positioning Attribute; Recording of previous events; Research; Research Design; Residual state; Risk; Risk Factors; Rupture; Shoulder; Skin; Stress; Thick; Time; Tissues; Toes; Ulcer; Walking; X-Ray Computed Tomography; ankle joint; crosslink; disability; extensor digitorum; follow-up; foot; high risk population; improved; improved functioning; innovation; joint mobilization; kinematics; patient mobility; pressure; prevent; primary outcome; programs; prospective; protein degradation; public health relevance; secondary outcome; successful intervention

DESCRIPTION (provided by applicant): The long term goal of this research is to reduce the incidence of lower extremity amputation in people with diabetes mellitus and peripheral neuropathy. It is hypothesized that muscle, joint, and movement deterioration associated with diabetes and peripheral neuropathy contribute to metatarsophalangeal joint (MTPJ) hyperextension deformity. MTPJ deformity results in excessive plantar stress on the insensitive forefoot, leading to ulceration and amputation. However, the specific cause of MTPJ deformity is not clear. The overall goal of this proposal is to identify the causes of MTPJ deformity and examine the ability of a targeted foot specific intervention to de-couple diabetes related mechanisms from MTPJ deformity and progression, following participants for 3 years. We hypothesizes that the cause of MTPJ deformity is an interaction of the accumulation of advanced glycation end products, muscle deterioration, limited joint mobility and compensatory movement strategies. The specific aims are to determine: 1) relationships between advanced glycation end products, intrinsic foot muscle volume, limited ankle dorsiflexion joint mobility, MTPJ hyperextension movement pattern, and MTPJ alignment; 2) estimate the effect of a foot specific intervention on the MTPJ extension alignment and 3) determine progression of MTPJ deformity and the predictors of progression over three years. The following will be collected on participants with diabetes mellitus and peripheral neuropathy and monitored over three years to understand the causes and progression of MTPJ deformity: 1) Skin intrinsic florescence to measure advanced glycation end product accumulation which increases collagen cross-linking and is associated with peripheral neuropathy, limited joint mobility, and muscle deterioration. 2) Magnetic resonance images to measure intrinsic foot muscle deterioration that precedes extrinsic foot muscle deterioration as a result of distal to proximal peripheral neuropathy. The muscle imbalance of weak intrinsic foot muscles, the only muscles able to flex the MTPJ, in the presence of relatively stronger extrinsic toe extensors, results in a force couple that hyperextends the MTPJ. 3) Kinematic and computed tomography measurement of foot and ankle joint positions to exam the mobility and movement patterns that contribute to repeated and extreme MTPJ hyperextension during daily activities. We believe advanced glycation end products lead to limited ankle joint dorsiflexion. As a result, there is increased reliance on the extensor digitorum longus to assist in dorsiflexing the stiff ankle joint during activities like si to stand. This study will have profound implications for reducing risk for skin breakdown and amputation by helping to understand and treat the causes of acquired neuropathic foot deformities. A successful foot specific intervention that improves MTPJ alignment will provide a non-invasive option to halt or slow the cascade of events leading to major lower extremity amputation, while improving function and minimizing disability.

描述（由申请人提供）：这项研究的长期目标是减少糖尿病患者和周围神经病患者下肢截肢的发生率。假设与糖尿病和周围神经病有关的肌肉，关节和运动恶化有助于Metasophangeal关节（MTPJ）过度伸展畸形。 MTPJ畸形会导致不敏感的前脚的足底应力过多，从而导致溃疡和截肢。但是，MTPJ畸形的特定原因尚不清楚。该提案的总体目标是确定MTPJ畸形的原因，并检查参与者在参与者3年后，从MTPJ畸形和进展中靶向的脚特异性干预对DE型糖尿病相关机制的能力。我们假设MTPJ畸形的原因是高级糖基化终产物的积累，肌肉恶化，有限的关节迁移率和补偿运动策略的相互作用。具体目的是确定：1​​）先进的糖基化最终产物，固有的脚部肌肉体积，有限的踝背屈关节迁移率，MTPJ过度伸展运动模式和MTPJ比对之间的关​​系； 2）估计脚特异性干预对MTPJ扩展比对的影响，3）确定MTPJ畸形的进展和三年内进展的预测因素。以下将收集到糖尿病和周围神经病的参与者中，并经过三年的监测以了解MTPJ畸形的原因和进展：1）皮肤固有的闪光以测量高级糖化最终产物积累的累积，从而增加了胶原蛋白交叉链接，从而增加了胶原蛋白的交叉链接，并增加了与外周神经疗法相关的限制性迁移率，并与限制性迁移率相关。 2）磁共振图像测量固有的脚部肌肉恶化，该肌肉衰弱是由于外周神经病近端而导致外部脚部肌肉恶化的。在相对较强的外部脚趾伸肌存在下，弱内在脚肌肉的肌肉失衡，唯一能够弯曲MTPJ的肌肉，导致一对夫妇过度伸展MTPJ。 3）运动和计算机断层扫描测量的脚和踝关节位置，以检查日常活动期间有助于重复和极端MTPJ过度XTENISION的活动性和运动模式。我们认为，先进的糖基化最终产品会导致踝关节背反射有限。结果，在像SI这样的活动期间，对伸肌长长的伸缩脚踝关节的依赖增加了。这项研究将通过帮助理解和治疗获得性神经性脚部畸形的原因来降低皮肤破裂和截肢的风险有深远的影响。改善MTPJ对准的成功脚的特定干预措施将提供一种无创的选择，以停止或减慢导致重大下肢截肢的事件的级联，同时改善功能并最大程度地减少残疾。