Peripheral neuropathy is a disabling complication of many conditions including diabetes, alcohol abuse, HIV infection, carpal tunnel syndrome, and chemotherapy for cancer. It is important to detect neuropathy early in the disease process, when potential for recovery is greatest and to initiate therapy to prevent or slow nerve degeneration. In neuropathy, sensory dysfunction almost always begins in the distal extremities (fingers or toes) where the sensation of touch is diminished or lost. Although quantitative sensory testing methods have been devised to assess cutaneous tactile and temperatures sensations objectively, there is no inexpensive, easy to use, and time efficient test to serve as a biomarker for early-stage peripheral neuropathy. The purpose of this proposal is to explore the utility of a novel approach to assess tactile sensation on the fingers in patients with peripheral neuropathy. We developed a new, objective, and sensitive device to detect impaired touch sensation early in nerve disease. In this test, referred to as the """"""""Bumps"""""""" test, the subject searches for small objects (bumps) of varying heights that are randomly placed on a flat surface. This approach will be tested in patients taking chemotherapy for cancer because many patients develop chemotherapy-induced neuropathy and, unlike most neuropathies, baseline measures can be obtained before treatment. In addition, cutaneous innervation will be assessed by skin biopsy and immunostaining of peripheral nerve to determine the relationship between a decrease in tactile sensitivity and innervation by myelinated and unmyelinated nerve fibers in the finger pad. The first specific aim will determine bump detection thresholds (bump height) as a function of sex and age in healthy subjects. We will also determine changes in bump detection in patients undergoing chemotherapy. It is hypothesized that bump detection threshold will increase over time in patients receiving chemotherapy. In the second aim, biopsies will be obtained from the same finger pad used in the psychophysical test in patients at various times during chemotherapy and when bump thresholds increase. It is hypothesized that increased bump detection thresholds will correlate with a decrease in the number of Meissner corpuscles and their myelinated nerve fibers early in disease. Identifying patients with early onset neuropathy may lead to altered dosage or a change of therapeutic agent before the neuropathy becomes painful and intolerable, which often leads to the cessation of therapy. The Bumps test is an inexpensive, portable, and time efficient device for early detection of peripheral neuropathy. In the future, the Bumps test can be used in other disease states.
Peripheral neuropathy is a disabling complication of many conditions including diabetes, alcohol abuse, HIV infection, carpal tunnel syndrome, and chemotherapy for cancer. In neuropathy, sensory dysfunction almost always begins in the distal extremities (fingers or toes) where the sensation of touch is diminished or lost. It is important to detect neuropathy early in the disease process, when potential for recovery is greatest and to initiate therapy to prevent or slow nerve degeneration. We devised a new, objective, and sensitive device to detect impaired touch sensation on the finger pads early in nerve disease. In this test, referred to as the """"""""Bumps"""""""" test, the subject searches for small objects (bumps) of varying heights that are randomly placed on a flat surface. This approach will be tested in patients taking chemotherapy for cancer because many patients develop chemotherapy- induced neuropathy and, unlike most neuropathies, baseline measures can be obtained before treatment. A skin biopsy will be obtained so we that can we can compare changes in touch sensitivity to the amount of nerve fibers in the skin. We hypothesize that a decrease in the ability to feel the bumps will correlate with a decrease in innervation of the skin. Identifying patients with early onset neuropathy may lead to altered dosage or a change of therapeutic agent before the neuropathy becomes painful and intolerable, which often leads to the cessation of therapy. If successful, the Bumps test will be an inexpensive, portable, and time efficient device for early detection of peripheral neuropathy. In the future, the Bumps test can be used to diagnose neuropathy in other disease states, such as diabetes, to track disease progression over time, and to assess therapeutic interventions.
| Boyette-Davis, Jessica A; Eng, Cathy; Wang, Xin S et al. (2012) Subclinical peripheral neuropathy is a common finding in colorectal cancer patients prior to chemotherapy. Clin Cancer Res 18:3180-7 |
| Kennedy, W R; Selim, M M; Brink, T S et al. (2011) A new device to quantify tactile sensation in neuropathy. Neurology 76:1642-9 |
| Selim, M M; Wendelschafer-Crabb, G; Redmon, J B et al. (2010) Gastric mucosal nerve density: a biomarker for diabetic autonomic neuropathy? Neurology 75:973-81 |
