Assessment of sudomotor function - Clinical Autonomic Research

Purpose

To review the currently available literature on clinical autonomic tests of sudomotor function.

Methods

We searched PubMED/MEDLINE for articles on technical principles and clinical applications of sudomotor tests with a focus on their drawbacks and perspectives in order to provide a narrative review.

Results

The quantitative sudomotor axon reflex sweat test (QSART) is the most widely used test of sudomotor function. The technique captures pathology with low intra- and inter-subject variability but is limited by technical demands. The thermoregulatory sweat test comprises topographic sweat pattern analysis of the ventral skin surface and allows differentiating preganglionic from postganglionic sudomotor damage when combined with a small fiber test such as QSART. The sympathetic skin response also belongs to the more established techniques and is used in lie detection systems due to its high sensitivity for sudomotor responses to emotional stimuli. However, its clinical utility is limited by high variability of measurements, both within and between subjects. Newer and, therefore, less widely established techniques include silicone impressions, quantitative direct and indirect axon reflex testing, sensitive sweat test, and measurement of electrochemical skin conductance. The spoon test does not allow a quantitative assessment of the sweat response but can be used as bedside-screening tool of sudomotor dysfunction.

Conclusion

While new autonomic sudomotor function testings have been developed and studied over the past decades, the most were well-studied and established techniques QSART and TST remain the gold standard of sudomotor assessment. Combining these techniques allows for sophisticated analysis of neurally mediated sudomotor impairment. However, newer techniques display potential to complement gold standard techniques to further improve their precision and diagnostic value.

1. Illigens BMW, Gibbons CH (2008) Sweat testing to evaluate autonomic function. Clin Auton Res 19(2):79. https://doi.org/10.1007/s10286-008-0506-8

   Article  PubMed  PubMed Central  Google Scholar 

2. Freeman R (2005) Autonomic peripheral neuropathy. Lancet 365(9466):1259–1270. https://doi.org/10.1016/S0140-6736(05)74815-7

   Article  CAS  PubMed  Google Scholar 

3. Low VA, Sandroni P, Fealey RD, Low PA (2006) Detection of small-fiber neuropathy by sudomotor testing. Muscle Nerve 34(1):57–61. https://doi.org/10.1002/mus.20551

   Article  PubMed  Google Scholar 

4. Hoeldtke RD, Bryner KD, Horvath GG, Phares RW, Broy LF, Hobbs GR (2001) Redistribution of sudomotor responses is an early sign of sympathetic dysfunction in type 1 diabetes. Diabetes 50(2):436–443

   Article  CAS  Google Scholar 

5. Folk GE Jr, Semken HA Jr (1991) The evolution of sweat glands. Int J Biometeorol 35(3):180–186

   Article  Google Scholar 

6. Zawadzka M, Szmuda M, Mazurkiewicz-Beldzinska M (2017) Thermoregulation disorders of central origin—how to diagnose and treat. Anaesthesiol Intensive Ther 49(3):227–234. https://doi.org/10.5603/ait.2017.0042

   Article  PubMed  Google Scholar 

7. Sato K, Kang WH, Saga K, Sato KT (1989) Biology of sweat glands and their disorders. I. Normal sweat gland function. J Am Acad Dermatol 20(4):537–563. https://doi.org/10.1016/S0190-9622(89)70063-3

   Article  CAS  PubMed  Google Scholar 

8. Machado-Moreira CA, Smith FM, van den Heuvel AMJ, Mekjavic IB, Taylor NAS (2008) Sweat secretion from the torso during passively-induced and exercise-related hyperthermia. Eur J Appl Physiol 104(2):265–270. https://doi.org/10.1007/s00421-007-0646-x

   Article  PubMed  Google Scholar 

9. Guttmann L (1947) The management of the quinizarin sweat test. Postgrad Med J 23(262):353–366

   Article  CAS  Google Scholar 

10. Low PA (2004) Evaluation of sudomotor function. Clin Neurophysiol 115(7):1506–1513. https://doi.org/10.1016/j.clinph.2004.01.023

    Article  PubMed  Google Scholar 

11. Morrison SF, Nakamura K (2011) Central neural pathways for thermoregulation. Front Biosci 16:74–104

    Article  CAS  Google Scholar 

12. Low PA, Tomalia VA, Park K-J (2013) Autonomic function tests: some clinical applications. J Clin Neurol 9(1):1–8

    Article  Google Scholar 

13. Low PA, Caskey PE, Tuck RR, Fealey RD, Dyck PJ (1983) Quantitative sudomotor axon reflex test in normal and neuropathic subjects. Ann Neurol 14(5):573–580. https://doi.org/10.1002/ana.410140513

    Article  CAS  PubMed  Google Scholar 

14. Gibbons CH, Illigens BM, Centi J, Freeman R (2008) QDIRT: quantitative direct and indirect test of sudomotor function. Neurology 70(24):2299–2304. https://doi.org/10.1212/01.wnl.0000314646.49565.c0

    Article  PubMed  PubMed Central  Google Scholar 

15. Freeman R, Chapleau MW (2013) Testing the autonomic nervous system. Handb Clin Neurol 115:115–136. https://doi.org/10.1016/B978-0-444-52902-2.00007-2

    Article  PubMed  Google Scholar 

16. Siepmann T, Illigens BM-W, Reichmann H, Ziemssen T (2014) Axon-reflex-basierte nervenmessverfahren in der diagnostik autonomer neuropathie. Der Nervenarzt 85(10):1309–1314. https://doi.org/10.1007/s00115-014-4120-9

    Article  CAS  PubMed  Google Scholar 

17. Sletten DM, Kimpinski K, Weigand SD, Low PA (2010) Comparison of a gel versus solution-based vehicle for the delivery of acetylcholine in QSART. Auton Neurosci 158(1):123–126. https://doi.org/10.1016/j.autneu.2010.05.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

18. Kennedy WR (2002) Usefulness of the silicon impression mold technique to evaluate sweating. Clin Auton Res 12(1):9–10

    Article  CAS  Google Scholar 

19. Siepmann T, Pinter A, Buchmann SJ, Stibal L, Arndt M, Kubasch AS, Kubasch ML, Penzlin AI, Frenz E, Zago W, Horvath T, Szatmari S Jr, Bereczki D, Takats A, Ziemssen T, Lipp A, Freeman R, Reichmann H, Barlinn K, Illigens BM (2017) Cutaneous autonomic pilomotor testing to unveil the role of neuropathy progression in early Parkinson’s disease (CAPTURE PD): protocol for a multicenter study. Front Neurol 8:212. https://doi.org/10.3389/fneur.2017.00212

    Article  PubMed  PubMed Central  Google Scholar 

20. Vinik AI, Nevoret ML, Casellini C (2015) The new age of sudomotor function testing: a sensitive and specific biomarker for diagnosis, estimation of severity, monitoring progression, and regression in response to intervention. Front Endocrinol 6:94. https://doi.org/10.3389/fendo.2015.00094

    Article  Google Scholar 

21. Mao F, Liu S, Qiao X, Zheng H, Xiong Q, Wen J, Zhang S, Zhang Z, Ye H, Shi H, Lu B, Li Y (2017) SUDOSCAN, an effective tool for screening chronic kidney disease in patients with type 2 diabetes. Exp Ther Med 14(2):1343–1350. https://doi.org/10.3892/etm.2017.4689

    Article  CAS  PubMed  PubMed Central  Google Scholar 

22. Dekker JM, Schouten EG, Klootwijk P, Pool J, Kromhout D (1994) Association between QT interval and coronary heart disease in middle-aged and elderly men. The Zutphen study. Circulation 90(2):779

    Article  CAS  Google Scholar 

23. Mayaudon H, Miloche PO, Bauduceau B (2010) A new simple method for assessing sudomotor function: relevance in type 2 diabetes. Diabetes Metab 36(6, Part 1):450–454. https://doi.org/10.1016/j.diabet.2010.05.004

    Article  CAS  PubMed  Google Scholar 

24. Novak P (2017) Electrochemical skin conductance: a systematic review. Clin Auton Res. https://doi.org/10.1007/s10286-017-0467-x

    Article  PubMed  PubMed Central  Google Scholar 

25. Loavenbruck AJ, Hodges JS, Provitera V, Nolano M, Wendelshafer-Crabb G, Kennedy WR (2017) A device to measure secretion of individual sweat glands for diagnosis of peripheral neuropathy. J Peripher Nerv Syst 22(2):139–148. https://doi.org/10.1111/jns.12212

    Article  CAS  PubMed  Google Scholar 

26. Vilches JJ, Wynick D, Kofler B, Lang R, Navarro X (2012) Sudomotor function and sweat gland innervation in galanin knockout mice. Neuropeptides 46(4):151–155. https://doi.org/10.1016/j.npep.2012.05.002

    Article  CAS  PubMed  Google Scholar 

27. Shahani BT, Halperin JJ, Boulu P, Cohen J (1984) Sympathetic skin response—a method of assessing unmyelinated axon dysfunction in peripheral neuropathies. J Neurol Neurosurg Psychiatry 47(5):536

    Article  CAS  Google Scholar 

28. Vetrugno R, Liguori R, Cortelli P, Montagna P (2003) Sympathetic skin response: basic mechanisms and clinical applications. Clin Auton Res 13(4):256–270. https://doi.org/10.1007/s10286-003-0107-5

    Article  PubMed  Google Scholar 

29. Gibbons C, Freeman R (2004) The evaluation of small fiber function-autonomic and quantitative sensory testing. Neurol clin 22(3):683–702. https://doi.org/10.1016/j.ncl.2004.03.002 vii

    Article  PubMed  Google Scholar 

30. Emad R, Zafarghasempour M, Roshanzamir S (2013) Sympathetic skin response in incomplete spinal cord injury with urinary incontinence. Ann Indian Acad Neurol 16(2):234–238. https://doi.org/10.4103/0972-2327.112479

    Article  PubMed  PubMed Central  Google Scholar 

31. Meijer EH, Smulders FTY, Johnston JE, Merckelbach HLGJ (2007) Combining skin conductance and forced choice in the detection of concealed information. Psychophysiology 44(5):814–822. https://doi.org/10.1111/j.1469-8986.2007.00543.x

    Article  PubMed  Google Scholar 

32. van Dooren M, de Vries JJ, Janssen JH (2012) Emotional sweating across the body: comparing 16 different skin conductance measurement locations. Physiol Behav 106(2):298–304. https://doi.org/10.1016/j.physbeh.2012.01.020

    Article  CAS  PubMed  Google Scholar 

33. Bors E (1964) Simple methods of examination in paraplegia: i. The spoon test. Paraplegia 2:17–19. https://doi.org/10.1038/sc.1964.4

    Article  CAS  PubMed  Google Scholar 

34. Tsementzis SA, Hitchcock ER (1985) The spoon test: a simple bedside test for assessing sudomotor autonomic failure. J Neurol Neurosurg Psychiatry 48(4):378

    Article  CAS  Google Scholar 

35. Khurana RK, Russell C (2017) The spoon test: a valid and reliable bedside test to assess sudomotor function. Clin Auton Res 27(2):91–95. https://doi.org/10.1007/s10286-017-0401-2

    Article  PubMed  Google Scholar 

Download references

Authors and Affiliations

1. Department of Neurology, Campus Virchow, Charite University Medicine Berlin, Berlin, Germany

   Sylvia J. Buchmann

2. Department of Neurology, Bavaria Hospital Kreischa, Kreischa, Germany

   Ana Isabel Penzlin

3. Department of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany

   Marie Luise Kubasch & Timo Siepmann

4. Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

   Ben Min-Woo Illigens

Contributions

SJB drafted the first version of the manuscript. AIP, MLK, BMW and TS have made substantial contributions to reviewing the manuscript for intellectual content, language and design. SJB, BMW and TS have made substantial contributions to drafting the figures displayed in this article.

Corresponding author

Correspondence to Timo Siepmann.

Conflict of interest

The authors have no financial conflicts of interests to report. Dr. Siepmann’s research is supported by grants from the Michael J. Fox Foundation, the German Parkinson’s Disease Association (DPG) and Prothena Biosciences. Dr. Illigens’ research is supported by grants from the Michael J. Fox Foundation.