A New Device for Rapid Measurement of Touch Sensation in neuropathy

描述（由申请人提供）： 周围神经病变是许多疾病的致残性并发症，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检测神经病变，此时恢复的潜力最大，并开始治疗以预防或减缓神经变性。在神经病中，感觉功能障碍几乎总是开始于远端肢体（手指或脚趾），其中触觉减弱或丧失。虽然已经设计了定量感觉测试方法来客观地评估皮肤触觉和温度感觉，但是没有便宜、易于使用和时间有效的测试来作为早期周围神经病变的生物标志物。 本建议的目的是探索一种新的方法来评估周围神经病变患者手指的触觉的效用。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受损的触觉。在该测试中，被称为“颠簸”测试，受试者搜索随机放置在平坦表面上的不同高度的小物体（颠簸）。这种方法将在接受化疗的癌症患者中进行测试，因为许多患者会发生化疗诱导的神经病变，并且与大多数神经病变不同，可以在治疗前获得基线测量。此外，将通过皮肤活检和外周神经免疫染色评估皮肤神经支配，以确定触觉敏感性降低与指垫中有髓和无髓神经纤维的神经支配之间的关系。 第一个特定目标将确定健康受试者中作为性别和年龄的函数的撞击检测阈值（撞击高度）。我们还将确定接受化疗的患者中肿块检测的变化。假设在接受化疗的患者中，碰撞检测阈值将随时间增加。在第二个目标中，活检将在化疗期间的不同时间和碰撞阈值增加时从患者的心理物理测试中使用的相同指垫获得。据推测，增加的碰撞检测阈值将与疾病早期迈斯纳小体及其有髓神经纤维数量的减少相关。 识别患有早发性神经病的患者可能会导致在神经病变得疼痛和无法忍受之前改变剂量或改变治疗剂，这通常会导致治疗停止。Bumps测试是用于早期检测周围神经病变的廉价、便携且省时的设备。将来，Bumps测试可以用于其他疾病状态。 公共卫生相关性：周围神经病变是许多疾病的致残性并发症，包括糖尿病、酗酒、HIV感染、腕管综合征和癌症化疗。在神经病中，感觉功能障碍几乎总是开始于远端肢体（手指或脚趾），其中触觉减弱或丧失。重要的是在疾病过程的早期检测神经病变，此时恢复的潜力最大，并开始治疗以预防或减缓神经变性。 我们设计了一种新的，客观的，灵敏的设备来检测受损的触觉在神经疾病的早期指垫。在该测试中，被称为“颠簸”测试，受试者搜索随机放置在平坦表面上的不同高度的小物体（颠簸）。这种方法将在接受化疗的癌症患者中进行测试，因为许多患者会发生化疗诱导的神经病变，与大多数神经病变不同，基线测量可以在治疗前获得。将获得皮肤活检，这样我们就可以比较触觉敏感度的变化与皮肤中神经纤维的数量。我们推测，感觉肿块的能力下降与皮肤神经支配的减少有关。 识别患有早发性神经病的患者可能会导致在神经病变得疼痛和无法忍受之前改变剂量或改变治疗剂，这通常会导致治疗停止。如果成功的话，Bumps测试将是一种便宜，便携，省时的早期检测周围神经病变的设备。在未来，Bumps测试可用于诊断其他疾病状态下的神经病变，如糖尿病，跟踪疾病随时间的进展，并评估治疗干预措施。

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.