Sweat testing to evaluate autonomic function

Abstract

Sudomotor dysfunction is common in many subtypes of neuropathy but is one of the earliest detectable neurophysiologic abnormalities in distal small fiber neuropathy. Clinical assessments of sudomotor function include thermoregulatory sweat testing (TST), quantitative sudomotor axon reflex testing (QSART), silicone impressions, the sympathetic skin response (SSR), the acetylcholine sweat-spot test and quantitative direct and indirect axon reflex testing (QDIRT). These testing techniques, when used in combination, can detect and localize pre- and postganglionic lesions, can provide early diagnosis of sudomotor dysfunction and can monitor disease progression or disease recovery. In this article, we describe many of the common clinical tests available for evaluation of sudomotor function with focus on the testing methodology and limitations while providing concrete examples of test results.

Figure 1. The sudomotor axon reflex

Cholinergic agonists (such as acetylcholine) applied through iontophoresis (shown with the black arrow) bind to muscarinic receptors causing local sweat production (dashed arrow). The cholinergic agonist simultaneously binds to nicotinic receptors on nerve terminals of sudomotor fibers and an impulse travels antidromically. At branch points this impulse travels orthodromically to a neighboring population of eccrine sweat glands causing an indirect axon mediated sweat response (dotted arrows).

Figure 2. Thermoregulatory sweat testing (TST)

A TST chamber is temperature and humidity controlled. Ceiling mounted infrared heaters control the patient’s temperature. The patient is placed in the supine position. Oral and cutaneous temperature probes are attached. During the application of the indicator dye, the patient’s eyes, nose and mouth should be protected. To achieve even distribution of the indicator powder, an atomizer should be used. The test is started by increasing the room temperature. Oral temperature must rise at least 1.0°C above baseline temperature or to 38 °C (whichever is higher). At the end of the test pictures are taken and used to generate a topographical map of the sweat pattern.

Figure 3. Thermoregulatory sweat test (TST) results

Normal sweat patterns show a sweat response present over the entire body that may be variable in intensity (A). In (B), a length dependent neuropathy from diabetes with stocking and glove distribution loss is seen. A patient with a complete myelopathy at T9 is shown in (C). Lesions to individual nerves can show focal or dermatomal sweat defects. A patient with a right T10 radiculopathy and a left lateral femoral cutaneous neuropathy can be identified in (D). A patient with complete anhidrosis secondary to pure autonomic failure is seen in (E).

Figure 4. Quantitative sudomotor axon reflex test (QSART)

An overview of the QSART testing procedure: A multi-compartmental sweat capsule has an outer ring (A, 1.5mm wide) for iontophoretic stimulation and an inner compartment (C, 1cm diameter) for measuring humidity. The stimulation and recording sites are separated by a small compartment (B, 1.5mm wide) to prevent direct stimulation of the sweat glands and leakage of the iontophoresis fluid. Dry nitrogen gas is released at a steady rate of flow (typically 100 cc/min) controlled through a flow meter. The gas flows through a temperature controlled heat exchanger and into the sweat capsule (C). Upon exiting the capsule the gas flows back through the heat exchanger and to a hygrometer, where changes in humidity are recorded on a computer.

Figure 5. QSART results

Panel (A), after a baseline is reached (1) recording is started for at least 2 minutes. Iontophoresis is started (2) at 2mA for 5 minutes (3). Recording is continued to monitor recovery for at least another 10 minutes (4) (A). Panel (B) shows a normal response. The example in (C) shows a “hung-up” response typically seen if sweat production is excessive and no recovery is reached. Panel (D) shows a reduced sweat response with a delayed onset of sweat production.

Figure 6. Silicone impressions

Sweat glands are stimulated via iontophoresis at 2mA for 5 minutes (A). Silicone compounds are mixed in equal parts, rolled out into a thin layer and applied on to the stimulated area until polymerization is reached (B). Toner powder is applied to the silicone imprint and the excess is removed by wiping the surface with alcohol swabs until only the sweat droplet imprints are stained (C). Panel (D) shows two typical imprints, with the male subject producing larger sweat output. Imprints are prone to artifacts, such as hair marks or air bubbles.

Figure 7. QDIRT: Quantitative direct and indirect reflex testing of sudomotor function

Sweat glands are stimulated via iontophoresis at 2mA for 5 minutes (A). Alizarin red powder is applied in a thin layer onto the stimulated area (B). Immediately, digital pictures are taken every 15 seconds for 7 minutes (C). The results can be quantified by droplet number, size, location and response latency in both direct and indirect testing regions.

Figure 8. The sympathetic skin response (SSR)

The figure shows examples of three normal recordings. After a stimulus (e.g. a deep breath) any deviation from the baseline is reported. If no change is seen, a stronger stimulus is applied (e.g. electrical stimulation) and if there is still no change seen, an “absent response” is reported. The onset latency and magnitude of response can be quantified, although the results are highly variable within and between subjects.