A New Device for Rapid Measurement of Touch Sensation in neuropathy

描述（由申请人提供）：周围神经病变是多种疾病的致残并发症，包括糖尿病、酗酒、HIV感染、腕管综合征和癌症化疗。重要的是在疾病过程的早期发现神经病变，此时恢复的潜力最大，并开始治疗以防止或减缓神经变性。在神经病变中，感觉功能障碍几乎总是始于远端肢体（手指或脚趾），在那里触觉减弱或丧失。虽然定量的感觉测试方法已经被设计用来客观地评估皮肤的触觉和温度感觉，但目前还没有一种廉价、易用、省时的测试来作为早期周围神经病变的生物标志物。本研究的目的是探索一种评估周围神经病变患者手指触觉的新方法。我们开发了一种新的、客观的、灵敏的设备来检测神经疾病早期的触觉受损。在这个被称为“颠簸”的测试中，受试者搜索随机放置在平面上的不同高度的小物体（颠簸）。这种方法将在接受癌症化疗的患者中进行测试，因为许多患者会出现化疗引起的神经病变，与大多数神经病变不同，治疗前可以获得基线测量。此外，皮肤神经支配将通过皮肤活检和周围神经免疫染色来评估，以确定触觉敏感性下降与指垫有髓和无髓神经纤维支配之间的关系。第一个具体目标是确定健康受试者的碰撞检测阈值（碰撞高度）作为性别和年龄的函数。我们还将确定化疗患者肿块检测的变化。据推测，肿块检测阈值将随着接受化疗的患者时间的推移而增加。在第二个目标中，将在化疗期间的不同时间和肿块阈值增加时，从患者的心理物理测试中使用的同一指垫进行活检。据推测，肿块检测阈值的增加与疾病早期迈斯纳小体及其髓鞘神经纤维数量的减少有关。发现早发性神经病变患者可能导致在神经病变变得疼痛和无法忍受之前改变剂量或改变治疗剂，这通常导致停止治疗。Bumps试验是一种廉价，便携，高效的设备，用于周围神经病变的早期检测。在未来，Bumps测试可以用于其他疾病状态。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: 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.