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

摘要

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.