Muscle, Joint and Movement Deterioration Contributing to Neuropathic Forefoot Deformity

描述(申请人提供)：这项研究的长期目标是减少糖尿病和周围神经病变患者的下肢截肢发生率。据推测，糖尿病和周围神经病变导致的肌肉、关节和运动能力的下降导致了跖趾关节(MTPJ)过度伸展畸形。MTPJ畸形会导致前脚感觉迟钝的足底应力过大，导致溃疡和截肢。然而，MTPJ畸形的具体原因尚不清楚。这项建议的总体目标是确定MTPJ畸形的原因，并检查有针对性的足部特异性干预的能力，以使糖尿病相关机制与MTPJ畸形和进展脱钩，对参与者进行3年的跟踪调查。我们假设MTPJ畸形的原因是晚期糖基化终末产物的积累、肌肉退化、有限的关节活动度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、固有足部肌肉容量、有限的踝关节背屈关节活动度、MTPJ过度伸展运动模式和MTPJ对齐之间的关系；2)评估足部特定干预对MTPJ伸展对齐的影响；3)确定MTPJ畸形的进展和三年后进展的预测因素。将收集糖尿病和周围神经病变参与者的以下数据，并在三年内进行监测，以了解MTPJ畸形的原因和进展：1)皮肤固有花期以测量晚期糖基化终末产物的积累，它增加了胶原的交联性，并与周围神经病变、关节活动受限和肌肉退化有关。2)磁共振成像测量由于远端近端周围神经病变而导致的外源性足部肌肉退化之前的内在足部肌肉退化。较弱的内在足部肌肉是唯一能够弯曲MTPJ的肌肉，在相对较强的外在脚趾伸展肌存在的情况下，肌肉失衡导致MTPJ过度伸展。3)运动学和计算机断层扫描测量足部和踝关节的位置，以检查在日常活动中导致重复和极端的MTPJ过度伸展的活动度和运动模式。我们认为晚期糖基化终末产物会导致踝关节背屈受限。因此，在像站立这样的活动中，人们越来越依赖指长伸肌来帮助背伸僵硬的脚踝关节。这项研究将通过帮助了解和治疗获得性神经性足部畸形的原因，对降低皮肤破裂和截肢的风险具有深远的意义。成功的足部特异性干预可以改善MTPJ对齐，这将提供一种非侵入性的选择，以阻止或减缓导致重大下肢截肢的一连串事件，同时改善功能并将残疾降至最低。

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.