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）：本研究的长期目标是降低糖尿病和周围神经病变患者下肢截肢的发生率。据推测，与糖尿病和周围神经病变相关的肌肉、关节和运动退化导致跖趾关节（MTPJ）过伸畸形。MTPJ畸形导致过度足底应力对不敏感的前足，导致溃疡和截肢。然而，MTPJ畸形的具体原因尚不清楚。该提案的总体目标是确定MTPJ畸形的原因，并检查有针对性的足部特异性干预的能力，以将糖尿病相关机制与MTPJ畸形和进展脱钩，随访参与者3年。我们推测MTPJ畸形的原因是晚期糖基化终产物的积累、肌肉退化、关节活动受限和代偿性运动策略的相互作用。具体目的是确定：1）晚期糖基化终末产物、固有足部肌肉体积、踝关节背屈关节活动受限、MTPJ过伸运动模式和MTPJ对线之间的关系; 2）估计足部特定干预对MTPJ伸展对线的影响; 3）确定MTPJ畸形的进展和3年内进展的预测因素。将在患有糖尿病和周围神经病变的受试者中收集以下信息，并监测三年以上，以了解MTPJ畸形的原因和进展：1）皮肤固有荧光，以测量晚期糖基化终产物积累，其增加胶原交联并与周围神经病变、关节活动受限和肌肉退化相关。2)磁共振成像测量由于远端到近端周围神经病变导致的内在足肌肉退化，先于外在足肌肉退化。在存在相对较强的外源性脚趾伸肌的情况下，弱的内在足部肌肉（唯一能够屈曲MTPJ的肌肉）的肌肉不平衡导致过度伸展MTPJ的力偶。3)足部和踝关节位置的运动学和计算机断层扫描测量，以检查日常活动中导致重复和极端MTPJ过度伸展的活动性和运动模式。我们认为晚期糖基化终产物导致踝关节背屈受限。因此，越来越多的依赖于伸趾长肌，以协助背屈僵硬的踝关节在活动，如si站。这项研究将有深远的影响，以减少皮肤破裂和截肢的风险，帮助了解和治疗后天神经性足畸形的原因。一个成功的足部特异性干预，改善MTPJ对齐将提供一个非侵入性的选择，以停止或减缓导致下肢大截肢的事件级联，同时改善功能和最大限度地减少残疾。