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Background
Sudomotor testing is used in the clinical setting to evaluate and document neuropathic disturbances that may be associated with pain. The quantitative sudomotor axon reflex test (QSART), thermoregulatory sweat test (TST), sympathetic skin responses, and silastic sweat imprints are tests of sympathetic cholinergic sudomotor function.
The QSART measures axon reflex-mediated sudomotor responses quantitatively and evaluates post-ganglionic sudomotor function. Recording is usually carried out from the forearm and 3 lower extremity skin sites to assess the distribution of post-ganglionic deficits. The QSART has a high sensitivity, specificity, and reproducibility.
The TST evaluates the distribution of sweating by a change in color of an indicator powder. The test has a high sensitivity, and its specificity for delineating the site of lesion is greatly enhanced when used in conjunction with QSART.
Sweat imprints are formed by the secretion of active sweat glands into a plastic (silastic) imprint. The test can determine sweat gland density, a histogram of sweat droplet size and sweat volume per area.
Widely used in the past, sympathetic skin response measures change in skin resistance following a random electric stimulation, and provides an index of sweat production. However, this is non-thermoregulatory sweat that occurs on the palms and soles, is of different pharmacological and physiologic properties, and involves somatic afferents. The medical literature proves that this test is of relatively low sensitivity and uncertain specificity, as compared to QSART.
Hoitsma et al (2003) reported that sympathetic skin responses testing appeared to be of little value in diagnosing small-fiber neuropathy in patients with sarcoidosis. On the other hand, Hoitsma et al (2004) noted that QSART is useful for diagnosing small fiber neuropathy.
Quattrini et al (2007) measured foot skin vasodilator responses to acetylcholine (Ach) and sodium nitroprusside (SNP) and vasoconstrictor responses to sympathetic stimulation in 5 healthy control subjects, 10 non-neuropathic diabetic (NND) patients, 10 diabetic patients with painless neuropathy (PLDN), and 8 diabetic patients with painful diabetic neuropathy (PDN). In PDN, there were significantly reduced responses to Ach (ANOVA, p = 0.003) and vasoconstrictor inspiratory gasp (ANOVA, p < 0.001) but not to SNP (not significant). Post-hoc analysis showed significant differences in Ach-induced vasodilation between PDN and non-diabetic control subjects (p < 0.05) as well as between PDN and NND (p < 0.05) but not PDN and PLDN (not significant). There were no significant differences for SNP-induced vasodilation. However, there were significant differences in the vasoconstrictor response between PDN and control, NND, and PLDN (p < 0.01). This study found an impairment of cutaneous endothelium-related vasodilation and C-fiber-mediated vasoconstriction in PDN. Inappropriate local blood flow regulation may have a role in the pathogenesis of pain in diabetic neuropathy. The authors stated that prospective studies are needed to determine the temporal relationship of these changes in relation to the emergence of neuropathic pain.
Presently, post-ganglionic sudomotor function is assessed by means of QSART or silicone impressions. Quantitative direct and indirect reflex testing (QDIRT) is a new technique for assessing post-ganglionic sudomotor function. This technique combines some of the advantages of silicone impressions and QSART by providing data on droplet number, droplet topographic distribution, and temporal resolution in direct and axon reflex-mediated regions.
Gibbons et al (2008) described their findings on the use of QDIRT for evaluating sudomotor function. In this study, sweating in 10 healthy subjects (3 women and 7 men) was stimulated on both forearms by iontophoresis of 10 % acetylcholine. Silicone impressions were made and topical indicator dyes were digitally photographed every 15 seconds for 7 minutes after iontophoresis. Sweat droplets were quantified by size, location, and percent surface area. Each test was repeated eight times in each subject on alternating arms over 2 months. Another 10 subjects (5 women and 5 men) had silicone impressions, QDIRT, and QSART performed on the dorsum of the right foot. The percent area of sweat photographically imaged correlated with silicone impressions at 5 minutes on the forearm (r = 0.92, p < 0.01) and dorsal foot (r = 0.85, p < 0.01). The number of sweat droplets assessed with QDIRT correlated with the silicone impression, although the droplet number was lower (162 +/- 28 versus 341 +/- 56, p < 0.01, r = 0.83, p < 0.01). The sweat response and sweat onset latency assessed by QDIRT correlated with QSART measured at the dorsum of the foot (r = 0.63, p < 0.05; r = 0.52, p < 0.05). The authors concluded that QDIRT measured both the direct and the indirect sudomotor response with spatial resolution similar to that of silicone impressions, and with temporal resolution similar to that of QSART. They noted that QDIRT provides a novel tool for the evaluation of post-ganglionic sudomotor function. Furthermore, they stated that more research is needed to ascertain the utility of QDIRT in disease states that alter sudomotor structure or function.
One limitation of QDIRT is that ambient room temperature and humidity need to be controlled to prevent cool dry air from causing evaporation of sweat production. Furthermore, normative values for QDIRT need to be established to avoid over-diagnosis of sudomotor dysfunction.
Peltier and colleagues (2010) stated that postural tachycardia syndrome (POTS) is a heterogeneous disorder characterized by excessive orthostatic tachycardia in the absence of orthostatic hypotension and by sympathetic nervous system activation. Post-ganglionic sudomotor deficits have been used to define a neurogenic POTS subtype. Norepinephrine levels above 600 pg/ml have also been used to delineate patients with a hyperadrenergic state. These reseachers determined the relationship of sudomotor abnormalities to other aspects of dysautonomia in POTS. Autonomic function was quantified in 30 women through tests of cardio-vagal, adrenergic, and sudomotor function including QSART and spectral indices. Differences between patients with and without sudomotor dysfunction as defined by QSART and between patients with and without hyperadrenergic POTS were assessed with Mann-Whitney U test and Mantel-Haenszel Chi-Square test using a p value of 0.01 for significance. Spearman correlation coefficients were used to test raw sweat volume correlations with other variables. Of 30 women (aged 20 to 58), 17 patients (56 %) had an abnormal QSART that was typically patchy and involved the lower extremity, while 13 patients had normal QSART results. Other autonomic tests, catecholamines or spectral indices did not correlate with QSART results. No differences in autonomic tests or spectral indices were observed between hyperadrenergic and non-hyperadrenergic POTS. The authors concluded that these findings confirmed that a large subset of POTS patients have sudomotor abnormalities that are typically patchy in distribution but do not correlate with other tests of autonomic function. They stated that further studies are needed to determine the best method of endophenotyping patients with POTS.
Manek and associates (2011) stated that the pathophysiological factors of primary Raynaud phenomenon (RP) are unknown. Preliminary evidence from skin biopsy suggests small-fiber neuropathy (SFN) in primary RP. In a pilot study, these investigators aimed to quantitatively assess SFN in patients with primary RP. Consecutive subjects with an a priori diagnosis of primary RP presenting to the authors' outpatient rheumatology clinic over a 6-month period were invited to participate. Cases of secondary RP were excluded. All participants were required to have normal results on nail-fold capillary microscopy. Assessment for SFN was performed with autonomic reflex screening, which includes QSART, and cardiovagal and adrenergic function testing, TST, and quantitative sensory test (QST) for vibratory, cooling, and heat-pain sensory thresholds. A total of 9 female subjects with a median age of 38 years (range of 21 to 46 years) and a median symptom duration of 9 years (range of 5 months to 31 years) were assessed. Three participants had abnormal results on QSART, indicating peripheral sudomotor autonomic dysfunction; 2 participants had evidence of large-fiber involvement with heat-pain thresholds on QST. Heart rate and blood pressure responses to deep breathing, Valsalva maneuver, and 70-degree tilt were normal for all participants. Furthermore, all participants had normal TST results. In total, 3 of the 9 participants had evidence of SFN. The presence of SFN raises the possibility that a subset of patients with primary RP have an underlying, subclinical small-fiber dysfunction. The authors concluded that these data open new avenues of research and therapeutics for this common condition. The findings of this small, pilot study need to be validated by well-designed studies.
Argiana et al (2011) noted that diabetic foot ulcers affect almost 5 % of the patients with diabetes and carry a huge physical, emotional, and financial burden. Almost 80 % of amputations in patients with diabetes are preceded by a foot ulcer. Simple tests (e.g., monofilament, tuning fork, vibration perception threshold determination, ankle reflexes, and pinprick sensation), alone or in combination, have been studied prospectively and can be used for identification of patients at risk. Newer tests examining sudomotor dysfunction and skin dryness have been introduced in recent years. In cross-sectional studies, sudomotor dysfunction assessed by either sympathetic skin response or Neuropad (Miro Verbandstoffe GmbH, Wiehl-Drabenderhöhe, Germany) testing has been consistently associated with foot ulceration. The authors concluded that prospective studies are needed to establish if sudomotor dysfunction can predict foot ulcers and if simple methods assessing sudomotor dysfunction (e.g., Neuropad testing) can be included in the screening tests for the prevention of this complication.
Guidelines from the American College of Occupational and Environmental Medicine (2008) make no recommendation for use of Quantitative Sudomotor Axon Reflex Test (QSART) to assist in the diagnostic confirmation of CRPS because of insufficient evidence.
An International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis’s practice guideline on “Chronic fatigue syndrome/myalgic encephalomyelitis” (2012) stated that “No specific diagnostic laboratory test is currently available for ME/CFS, although potential biomarkers are under investigation”.
Siepmann et al (2012) noted that although piloerector muscles are innervated by the sympathetic nervous system, there are at present no methods to quantify pilomotor function. In a pilot study, these researchers quantified piloerection using phenylephrine hydrochloride in humans. A total of 22 healthy volunteers (18 males, 4 females) aged 24 to 48 years participated in 6 studies. Piloerection was stimulated by iontophoresis of 1 % phenylephrine. Silicone impressions of piloerection were quantified by number and area. The direct and indirect responses to phenylephrine iontophoresis were compared on both forearms after pre-treatment to topical and subcutaneous lidocaine and iontophoresis of normal saline. Iontophoresis of phenylephrine induced piloerection in both the direct and axon reflex-mediated regions, with similar responses in both arms. Topical lidocaine blocked axon reflex-mediated piloerection post-iontophoresis (mean [SD], 66.6 [19.2] for control impressions versus 7.2 [4.3] for lidocaine impressions; p < 0.001). Subcutaneous lidocaine completely blocked piloerection. The area of axon reflex-mediated piloerection was also attenuated in the lidocaine-treated region post=iontophoresis (mean [SD], 46.2 [16.1]cm2 versus 7.2 [3.9]cm2; p < 0.001). Piloerection was delayed in the axon reflex region compared with the direct region. Normal saline did not cause piloerection. The authors concluded that phenylephrine provoked piloerection directly and indirectly through an axon reflex-mediated response that is attenuated by lidocaine. Piloerection is not stimulated by iontophoresis of normal saline alone. They stated that the quantitative pilomotor axon reflex test (QPART) may complement other measures of cutaneous autonomic nerve fiber function.
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