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

摘要 这STTR第一阶段重新提交描述了一个小，看似简单，便携式设备，称为 “速度颠簸”，迅速量化的感觉扑在脚上，脚趾或手指， 微米（µm）单位。颤振频率为20至30 Hz，低于近似下限 振动范围为40至50 Hz。这种高灵敏度的设备旨在区分小 健康受试者之间存在的扑动感觉的变化，并检测 周围神经病患者的足部感觉。 Speed Bumps设备旨在早期诊断神经病变， 逆转率最高;并监测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， 现在可能。 该装置是一个细长的塑料标尺，上面放置了一组高度不同的凸起平行脊 垂直于它的长度。脊群的高度从40微米到1微米不等 µm。在皮肤上来回摩擦脊状物会产生一种模仿身体的颤动感觉 高速公路减速带或隆隆声带产生的感觉。接触的大面积皮肤 不同高度的脊组产生了一系列的刺激强度，从几乎检测不到的， 需要测量健康人脚趾对更强刺激的阈值刺激 严重神经病变患者可以识别的最高脊。颤动激发了 表皮中的迈斯纳小体（MC）受体是平衡的重要受体 在许多日常活动中进行维护。 我们将扑动阈值定义为脚、脚趾、 或手指。正常受试者在20秒内检测到手指上的脊高度<8 µ m， 在60秒之内把脚和脚趾都清理干净这种灵敏度超过了目前的测试，并允许快速早期 神经损伤的检测和分级。 在第一阶段，我们将建立一个新的原型的减速带装置，并显示可行性， 测量健康成年人和糖尿病患者的小队列的扑动阈值 神经病变和化疗引起的周围神经病变（CIPN）。CIPN特别适用于 测试这种新设备，因为从病人假定正常到 化疗前的感觉和治疗期间严重的麻木发生在 周这使我们能够在神经病变进展期间以短时间、低成本的方式测试该设备。 study.早期诊断对CIPN患者是有益的，因为它使治疗医生能够早期诊断CIPN。 在恢复潜力最大的时候和在恢复之前， 疼痛性神经病的发作阻止了治疗的继续。 该STTR项目是对2009年3月NCI报告的回应，该报告引用了快速、敏感、成本 节省了在当地家庭环境中测试CIPN患者的方法。

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.