34 Sudoscan/EZSCAN Sudoscan measures the electrochemical skin conductance (ESC). Two nickel electrodes are placed on the subject’s hands and feet. The electrodes alternate between cathode and anode. The anode supplies a low DC-current, which results in a voltage (<4V) to the cathode. Consequently, a current starts to run, with the amplitude related to the concentration of chloride ions. The concentration of chloride ions depends on the height of the applied current and influences the ESC. ESC is determined from the derivative current associated with corresponding applied voltage, which is expressed in microSiemens (µS). Since patients with SFN show anhidrosis, lower concentration of chloride ions results into decreased conductance. As a result, patients with impaired small fiber function, show lower ESC to the corresponding voltage.77 Laser Doppler Imaging flare (LDIflare) LDIflare assesses the indirect axon reflex mediated blood flow on the foot. The subject acclimates in a room of 25±1 0C. With the use of a 0.64 cm2 skin heater, the skin on the foot is heated up to 440C. Within 20 minutes, maximal hyperemia is achieved and can be assessed with the use of laser Doppler imaging (LDI). An area of 3.5 cm2 surrounding the heated skin is scanned to measure the axon reflex mediated blood flow. The axon reflex mediated blood flow is an autonomic function innervated by small nerve fibers. The LDIflare area is calculated with software and expressed in cm2. LDImax is the mean flux in the area of the skin heater. LDIflare and LDImax are expressed in arbitrary perfusion units.130 LDIflare is reduced in diabetic patients compared to healthy controls and correlates with NFD.131 Neuropad Neuropad is a bandage containing Cobalt II compound. Sweat production causes Cobalt II compound to change from blue to pink. The time required to change the color of all Cobalt compound is a measure of sudomotor function. Sudomotor dysfunction is reported when the required time interval of at least one foot, is above 10 minutes. Advantages of the Neuropad are fast results, its non-invasive nature, simplicity and a high sensitivity132,133. Furthermore, it can be used to stage134 and predict135 neuropathy. Skin wrinkling Water-induced skin wrinkling (WISW) is a reliable sympathetic nerve function test. One hand of the subject is placed in 400C water for 30 minutes. In order to assess skin wrinkling, both hands are compared with each other. The wrinkle can be subdivided into five grades, with grade 0, no wrinkling and grade 4, wrinkling completely distorting the fingertip.136 Warm water induces vasoconstriction resulting in a negative digit pulp pressure. The pressure gradient between superficial and deep skin structures, results in a downward pull of the overlying skin. Due to the internal structures, skin folding presents.137 Sympathetic nerve fiber dysfunction prevents vasoconstriction. As a result, skin wrinkling remains absent after exposure to warm water.137 Sympathetic noradrenergic test Quantitative Pilomotor Axon-Reflex Test (QPART) The pilomotor axon-reflex test is a unique axon-reflex test, since it is activated by the noradrenergic sympathetic nerves. Iontophoresis with phenylephrine results in local direct and indirect piloerection. The line connecting the most peripheral edges of erected hairs is the outline of the total area. The indirect area can be calculated by subtracting the area of phenylephrine application from the outline area. A local topographic map is created with the use of silicone impressions. Limited literature is available to determine whether this test is able to diagnose SFN.138,139 2 36 2
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