"Speed Bumps": A non-invasive quantitative test for early detection of neuropathy in the feet

摘要 STTRI阶段重新提交描述了一种小型的、看似简单的便携设备，称为 快速量化脚部、脚趾或手指拍打的感觉的“减速带” 千分尺(微米)单位。颤振频率为20至30赫兹，低于近似下限 振动范围为40至50赫兹。这种高灵敏度设备的设计是为了区分小的 健康受试者之间存在的颤动感觉的变化和检测颤动感觉的减少 周围神经病患者脚部的感觉。 减速带设备旨在非常早地诊断神经病变，当潜在的 逆转是最高的；监测从研究中出现的新疗法的有效性 分子遗传学、药理学、纳米技术和其他令人兴奋的领域 现在有可能了。 该装置是一把细长的塑料尺子，上面放置着一组不同高度的平行凸起的脊线 垂直于它的长度。脊组的高度从高40微米到低1微米不等 在皮肤上来回摩擦脊部，产生一种模仿身体的扑动感觉 高速公路上的减速带或隆隆声产生的感觉。接触到的大面积皮肤区域 一组不同高度的脊线创造了一系列刺激强度，从几乎察觉不到的 需要测量健康人脚趾对更强刺激的阈值刺激 严重神经病患者可以识别的最高脊线。颤动让人兴奋 真皮浅层的触觉小体(MC)受体是维持平衡的重要受体 在许多日常活动中进行维护。 我们将颤振阈值定义为脚、脚趾、 或者手指。正常受试者在20秒内检测到手指脊线高度为8微米，打开时为8微米。 脚和脚趾在60秒内完成。这种敏感性超过了目前的测试，并允许快速及早 神经损伤的检测和分级。 在第一阶段，我们将建造一个新的减速带装置原型，并通过以下方式展示其可行性 健康成人和糖尿病患者小队列颤动阈值的测量 神经病和化疗所致的周围神经病(CIPN)。CIPN特别适用于 测试这种新设备是因为患者推定正常 化疗前的感觉和治疗期间出现的严重麻木 几周。这使我们能够在短时间内、成本效益高的情况下在神经病变进展期间测试该设备 学习。早期诊断对CIPN患者是有益的，因为它使治疗医生及早 有机会在康复潜力最大的时候修改治疗方案 出现痛性神经病变会阻止继续治疗。 该STTR项目回应了NCI 2009年3月的一份报告，该报告指出需要快速、敏感、成本 节约方法在当地家庭环境中对CIPN患者进行测试。

ABSTRACT This STTR Phase I resubmission describes a small, deceptively simple, portable device, called “Speed Bumps” that rapidly quantifies the sensation of flutter on the feet, toes or fingers in micrometer (µm) units. Flutter frequency is 20 to 30 Hz, which is below the approximate lower vibration range of 40 to 50 Hz. This high sensitivity device is designed to differentiate the small variations of flutter sensation that exist between healthy subjects and detect the reduction of sensation in the feet of persons with peripheral neuropathy. The Speed Bumps device is designed to diagnose neuropathy very early, when the potential for reversal is highest; and to monitor the effectiveness of new therapies appearing from research in molecular genetics, pharmacology, nanotechnology and other exciting fields to a degree that is not now possible. The device is a slender plastic ruler with groups of raised parallel ridges of different heights placed perpendicular to its length. Heights of the groups of ridges range from a high of 40 µm to a low of 1 µm. Rubbing the ridges to and fro on the skin creates a flutter sensation that mimics the body sensations produced by highway speed bumps or rumble strips. The large skin area contacted by groups of different height ridges creates a range of stimulus strengths, from barely detectable as needed to measure the threshold stimulus of the toes of healthy persons to a stronger stimulus by the highest ridges that can be recognized by patients with severe neuropathy. Flutter excites the Meissner corpuscle (MC) receptors in the superficial dermis that are important receptors for balance maintenance during many daily activities. We define the flutter threshold as the smallest set of ridges that can be detected by the foot, toes, or fingers. Normal subjects detect ridge heights <8 µm on the fingers in < 20 seconds and <8 µm on the feet and toes in 60 seconds. This sensitivity exceeds that of current tests and allows rapid early detection and grading of nerve damage. In Phase I we will build a new prototype of the Speed Bumps device and show feasibility by measuring the flutter thresholds of small cohorts of healthy adults and of patients with diabetic neuropathy and chemotherapy induced peripheral neuropathy (CIPN). CIPN is especially useful for testing this new device because the time elapsed between the patient having presumed normal sensation before chemotherapy and developing severe numbness during therapy occurs within weeks. This allows us to test the device during progression of neuropathy in a short, cost efficient study. Early diagnosis is beneficial for CIPN patients because it gives treating physicians an early opportunity to modify treatment at a time when the potential for recovery is greatest and before the onset of painful neuropathy prevents continuation of treatment. This STTR project responds to a March 2009 NCI report that cites a need for rapid, sensitive, cost saving methods to test patients with CIPN in their local home environment.