Electrochemical skin conductance

Electrochemical skin conductance (ESC) is an objective, non-invasive and quantitative electrophysiological measure. It is based on reverse iontophoresis and (multiple) steady chronoamperometry (more specifically chronovoltametry).

ESC is intended to provide insight into and assess sudomotor (or sweat gland) function  and small fiber peripheral neuropathy.

Description of the ESC measurement

Currently, ESC measurement can be obtained with the use of a medical device, called Sudoscan.[1][2]

No specific patient preparation or medical personnel training is required. The measure lasts less than 3 minutes, and is innocuous and non-invasive.

The apparatus consists of stainless-steel electrodes for the hands and the feet which are connected to a computer for recording and data management purposes. To conduct an ESC test, the patients place their hands and feet on the electrodes. Sweat glands are most numerous on the palms of the hands and soles of the feet, and thus well suited for sudomotor function evaluation.

The electrodes are used alternatively as anode or cathode. A direct current (DC) incremental voltage under 4 volts is applied on the anode. This DC, through reverse iontophoresis, induces a voltage on the cathode and generates a current (of an intensity less than 0.3 mA) between the anode and the cathode, related to electro-active ions from sweat reacting with the electrodes. The electrochemical phenomena are measured by the two active electrodes (the anode and the cathode) successively in the two active limbs (either hands or feet), whilst the two passive electrodes allow retrieval of the body potential.

During the test, 4 combinations of 15 different low DC voltages are applied. The resulting Electrochemical Skin Conductances (ESC) for each hand and foot are expressed in µS (micro-Siemens). The test also evaluates the percentage of asymmetry between the left and right side, for both hands and feet ESC, providing an assessment of whether one side is more affected than the other.

Applications

From a physiological standpoint, the pattern of innervation of the sweat gland—namely, the postganglionic sympathetic nerve fibers—allows clinicians and researchers to use sudomotor function testing to assess dysfunction of the autonomic nervous systems (ANS).

To ensure optimal use and interpretation of the ESC, normative values were defined in adults[3] and children.[4] In addition, reproducibility of the method was assessed under clinical conditions, including both healthy controls and patients with common chronic conditions.[5]

ESC has clinical utility in the evaluation and follow-up of dysautonomia and small fiber peripheral neuropathy which may occur in diseases such as:

Diabetes

Diabetes and two of its main complications: diabetic neuropathy[6][1][7] and autonomic neuropathy.[8] Sensorimotor polyneuropathy (DSPN) is the most common type of polyneuropathy in community-dwelling patients with diabetes, affecting about 25% of them.  The course of DSPN is insidious, though, and up to 50% of patients with neuropathy may be asymptomatic, often resulting in delayed diagnosis. Advanced or painful DSPN may result not only in reduced quality of life, but has been statistically associated with retinopathy and nephropathy, and leads to considerable morbidity and mortality.[9]  The autonomic nervous system (ANS), of which sudomotor nerves are an integral part, is the primary extrinsic control mechanism regulating heart rate, blood pressure, and myocardial contractility. Cardiac autonomic neuropathy (CAN) describes a dysfunction of the ANS and its regulation of the cardiovascular system. CAN is the strongest predictor for mortality in diabetes.[10][11]  Because early symptoms of CAN tend to be nonspecific, its diagnosis is frequently delayed and screening for CAN should be routinely considered in diabetic patients. Assessment of sudomotor function provides a measure of sympathetic cholinergic function in the workup of CAN.

Amyloidosis

Amyloidosis such as familial amyloid neuropathy,[12][13] AL amyloidosis,[14] and AA amyloidosis [publication pending]. During the course of AL amyloidosis, peripheral neuropathy occurs in 10–35% of patients; dysautonomia itself is an independent prognostic factor, and assessment of sweat disturbances is routine in the evaluation of amyloidosis.  ESC may provide a measure of subclinical autonomic involvement, which is not systematically assessed with more sophisticated equipment.

Cystic fibrosis

The effects of cystic fibrosis on sweat glands were described by Quinton.[15] The performance and potential utility of ESC were assessed in this disease.[16]

Parkinson’s disease

Assessment of dysautonomia is important for patient follow-up and assessment of sudomotor function can be helpful in daily practice.[17][18]

Chemotherapy-induced peripheral neuropathy (CIPN)

Chemotherapy-induced peripheral neuropathy is a common, potentially severe and dose-limiting adverse effect of multiple chemotherapeutic agents.  CIPN can persist long after the completion of chemotherapy and imposes a significant quality of life and economic burden to cancer survivors.  ESC allows for an objective quantification of small fiber impairment and is easy to implement in the clinic.[19][20]

Sjögren syndrome

ESC may help in the diagnosis process.[21][22]

Neuropathic pain

Neuropathic pain usually manifests in the setting of small fiber neuropathy. Small fiber neuropathy is common and may arise from a number of conditions such as diabetes, metabolic syndrome, infectious diseases, toxins, and autoimmune disorders. The gold standard for diagnosing small fiber neuropathy as the etiology of neuropathic pain is skin biopsy. Sudomotor assessment, an accurate objective technique, could be considered as a good screening tool to limit skin biopsy in patients in whom it is not suitable.[23][24]

ESC has been evaluated for both early diagnosis of small fiber neuropathy and follow-up of treatment efficacy in each of these conditions.[25][26][27][28]

Foundations: the eccrine sweat glands

See also sweat gland, eccrine sweat gland and Autonomic nervous system.

The ESC measurement relies on the particularities of the outer-most layer of the human skin, the stratum corneum (SC), which consists of a lipid corneocyte matrix crossed by skin appendages (sweat glands and their follicles). See.[29]

According to Chizmadzhev,[29] the stratum corneum is electrically insulating against DC voltages under 10V and only its appendageal pathways are conductive.

In the hairless skin, such as the palms of the hands and soles of the feet, in contact with the electrodes, the eccrine sweat glands are the principal conductive pathways.

These sweat glands are innervated by the sympathetic autonomic peripheral nervous system.  According to Sato,[30] both adrenergic and cholinergic-muscarinic neurons participate, in the following physiological proportions: adrenergic 2/7 and cholinergic 5/7.

Particularities of the autonomic sympathetic nerve fibers that innervate sweat glands are that they are long (the postganglionic nerves start at the spinal cord and may end at the palm or sole), thin, unmyelinated or thinly myelinated C fibers. Because of these characteristics, they are prone to damage early in many neuropathic processes; assessing sweat gland nerve function, or dysfunction, therefore, can be used as a surrogate for the damage imparted to small caliber sensory nerves in neuropathy.

Stimulation of sweat function

See Sudomotor function.

Physiological

During normal physiological function, activation of eccrine sweat glands starts with a “chemical” stimulus. For instance, in the cholinergic pathway (the dominant pathway), this leads to the following sequence, or activation cascade:[31]

  1. The neurotransmitter acetylcholine binds to its corresponding muscarinic cholinergic receptor on the membrane cells of the sweat gland wall;
  2. This activates the G proteins coupled to the neuroreceptor;
  3. The G proteins, or their intracellular messengers, then modulate ion channels, creating an ion flux through the membrane;
  4. This polarizes the gland to voltages around 10 mV and always less than 100mV electrical potential difference between the two sides of the gland wall[32]

Technological

For the purposes of measuring Electrochemical Skin Conductance, the sweat glands are activated with an “electrical” stimulus. The applied voltage directly polarizes the gland with voltages between 100 mV to 1000 mV. This induces ion fluxes across the gland wall, depending on the electrochemical gradient of the ions. Because the current applied is high compared to the physiological current, the test could be compared to a “stress test” for sweat glands.

In fact, firm application of the hands and feet against the electrodes blocks physiological sweating, and the active measure extracts electro-active ions (i. e., chloride near the anode, proton near the cathode) and pulls them towards the electrodes.

Alternative methods and technologies

There are several other clinical tests available to assess sudomotor and/or small fiber function[33][23] and/or peripheral or cardiac neuropathy.[34] These may employ a measurement target other than the sweat glands, and/or alternate methodologies.

For sudomotor tests, see Sudomotor function; specific clinical assessments include:

  • Sympathetic Skin Response (SSR),[35] defined as the variation in electrical potential of the skin due to sympathetic sudomotor outflow,
  •  Quantitative Sudomotor Axon Reflex Testing (QSART)[36][37]
  • A medical device, called Neuropad[38] which measures sweat production based on a color change in a cobalt II compound from blue to pink to produce a categorical output, semi-quantitative,
  • Skin Conductance Response (SCR) or Electrodermal activity (EDA).

References

  1. 1 2 Casellini, C. M.; Parson, H. K.; Richardson, M. S.; Nevoret, M. L.; & Vinik, A. I. (2013). "Sudoscan, a noninvasive tool for detecting diabetic small fiber neuropathy and autonomic dysfunction". Diabetes Technology & Therapeutics. 15 (11): 948–953. doi:10.1089/dia.2013.0129. PMC 3817891. PMID 23889506.
  2. ↑ Khalfallah, Kamel; Calvet, Jean-Henri; Brunswick, Philippe; Névoret, Marie-Laure; Ayoub, Hanna; Cassir, Michel (2020). "A Simple and Accurate Method to Assess Autonomic Nervous System through Sudomotor Function". In Yurish, Sergey (ed.). Advances in Biosensors: Reviews, Volume 3 (PDF). IFSA Publishing, S.L. pp. 149–204. ISBN 978-84-09-25125-4.
  3. ↑ Vinik, A. I.; Smith, A. G.; Singleton, J. R.; Callaghan, B.; Freedman, B. I.; Tuomilehto, J.; ... & Roche, F. (2016). "Normative values for electrochemical skin conductances and impact of ethnicity on quantitative assessment of sudomotor function". Diabetes Technology & Therapeutics. 18 (6): 391–398. doi:10.1089/dia.2015.0396. hdl:2027.42/140359. PMID 27057778.
  4. ↑ Leclair-Visonneau, L.; Bosquet, T.; Magot, A.; Fayet, G.; Gras-Le Guen, C.; Hamel, A.; & Péréon, Y. (2016). "Electrochemical skin conductance for quantitative assessment of sweat function: Normative values in children". Clinical Neurophysiology Practice. 1: 43–45. doi:10.1016/j.cnp.2016.07.001. PMC 6123897. PMID 30214959.
  5. ↑ Bordier, L.; Dolz, M.; Monteiro, L.; Névoret, M. L.; Calvet, J. H.; & Bauduceau, B. (2016). "Accuracy of a rapid and non-invasive method for the assessment of small fiber neuropathy based on measurement of electrochemical skin conductances". Frontiers in Endocrinology. 7: 18. doi:10.3389/fendo.2016.00018. PMC 4770015. PMID 26973597.
  6. ↑ Selvarajah, D.; Kar, D.; Khunti, K.; Davies, M. J.; Scott, A. R.; Walker, J.; & Tesfaye, S. (2019). "Diabetic peripheral neuropathy: advances in diagnosis and strategies for screening and early intervention" (PDF). The Lancet Diabetes & Endocrinology. 7 (12): 938–948. doi:10.1016/S2213-8587(19)30081-6. PMID 31624024.
  7. ↑ Yajnik, C. S.; Kantikar, V.; Pande, A.; Deslypere, J. P.; Dupin, J.; Calvet, J. H.; & Bauduceau, B. (2013). "Screening of cardiovascular autonomic neuropathy in patients with diabetes using non-invasive quick and simple assessment of sudomotor function". Diabetes & Metabolism. 39 (2): 126–131. doi:10.1016/j.diabet.2012.09.004. PMID 23159130.
  8. ↑ d'Amato, C.; Greco, C.; Lombardo, G.; Frattina, V.; Campo, M.; Cefalo, C. M.; ... & Spallone, V. (2020). "The diagnostic usefulness of the combined COMPASS 31 questionnaire and electrochemical skin conductance for diabetic cardiovascular autonomic neuropathy and diabetic polyneuropathy". Journal of the Peripheral Nervous System. 25 (1): 44–53. doi:10.1111/jns.12366. PMID 31985124. S2CID 210924747.
  9. ↑ Lim, L. L.; Fu, A. W.; Lau, E. S.; Ozaki, R.; Cheung, K. K.; Ma, R. C.; ... & Kong, A. P. (2019). "Sudomotor dysfunction independently predicts incident cardiovascular–renal events and all-cause death in type 2 diabetes: the Joint Asia Diabetes Evaluation register". Nephrology Dialysis Transplantation. 34 (8): 1320–1328. doi:10.1093/ndt/gfy154. PMC 6680097. PMID 29939305.
  10. ↑ Pop-Busui, R.; Evans, G. W.; Gerstein, H. C.; Fonseca, V.; Fleg, J. L.; Hoogwerf, B. J.; ... & ACCORD Study Group (2010). "Effects of cardiac autonomic dysfunction on mortality risk in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial". Diabetes Care. 33 (7): 1578–1584. doi:10.2337/dc10-0125. PMC 2890362. PMID 20215456.
  11. ↑ Maser, R. E.; Mitchell, B. D.; Vinik, A. I.; & Freeman, R. (2003). "The association between cardiovascular autonomic neuropathy and mortality in individuals with diabetes: a meta-analysis". Diabetes Care. 26 (6): 1895–1901. doi:10.2337/diacare.26.6.1895. PMID 12766130.
  12. ↑ Lefaucheur, J. P.; Zouari, H. G.; Gorram, F.; Nordine, T.; Damy, T.; & Planté-Bordeneuve, V. (2018). "The value of electrochemical skin conductance measurement using Sudoscan® in the assessment of patients with familial amyloid polyneuropathy". Clinical Neurophysiology. 129 (8): 1565–1569. doi:10.1016/j.clinph.2018.05.005. PMID 29883834. S2CID 47011006.
  13. ↑ Castro, J.; Costa, J.; de Castro, I.; & Conceição, I. (2018). "Electrochemical skin conductance in hereditary amyloidosis related to transthyretin V30M–a promising tool to assess treatment efficacy?". Amyloid. 25 (4): 267–268. doi:10.1080/13506129.2018.1545639. PMID 30773060. S2CID 73476147.
  14. ↑ Montcuquet, A.; Duchesne, M.; Roussellet, O.; Jaccard, A.; & Magy, L. (2020). "Electrochemical skin conductance values suggest frequent subclinical autonomic involvement in patients with AL amyloidosis". Amyloid: The International Journal of Experimental and Clinical Investigation. 27 (3): 215–216. doi:10.1080/13506129.2020.1757423. PMID 32351131. S2CID 217548350.
  15. ↑ Quinton, P. M. (2007). "Cystic fibrosis: lessons from the sweat gland". Physiology. 22 (3): 212–225. doi:10.1152/physiol.00041.2006. PMID 17557942.
  16. ↑ Hubert, D.; Brunswick, P.; Calvet, J. H.; Dusser, D.; & Fajac, I. (2011). "Abnormal electrochemical skin conductance in cystic fibrosis". Journal of Cystic Fibrosis. 10 (1): 15–20. doi:10.1016/j.jcf.2010.09.002. PMID 20920895.
  17. ↑ Pavy-LeTraon, A.; Brefel-Courbon, C.; Dupouy, J.; Ory-Magne, F.; Rascol, O.; & Senard, J. M. (2018). "Combined cardiovascular and sweating autonomic testing to differentiate multiple system atrophy from Parkinson's disease". Neurophysiologie Clinique. 48 (2): 103–110. doi:10.1016/j.neucli.2017.11.003. PMID 29249575. S2CID 207098455.
  18. ↑ Xu, X.; Liao, J.; Dong, Q.; Qin, F.; Li, J.; Sun, X.; ... & Qiu, W. (2019). "Clinical utility of SUDOSCAN in predicting autonomic neuropathy in patients with Parkinson's disease". Parkinsonism & Related Disorders. 64: 60–65. doi:10.1016/j.parkreldis.2019.03.007. PMID 30890381.
  19. ↑ Saad, M.; Psimaras, D.; Tafani, C.; Sallansonnet-Froment, M.; Calvet, J. H.; Vilier, A.; ... & Ricard, D. (2016). "Quick, non-invasive and quantitative assessment of small fiber neuropathy in patients receiving chemotherapy". Journal of Neuro-Oncology. 127 (2): 373–380. doi:10.1007/s11060-015-2049-x. PMID 26749101. S2CID 19058905.
  20. ↑ Delmotte, J. B.; Tutakhail, A.; Abdallah, K.; Reach, P.; D’Ussel, M.; Deplanque, G.; ... & Coudoré, F. (2018). "Electrochemical skin conductance as a marker of painful oxaliplatin-induced peripheral neuropathy". Neurology Research International. 2018: 1–9. doi:10.1155/2018/1254602. PMC 6186322. PMID 30363900.
  21. ↑ Zouari, H. G.; Wahab, A.; Ng Wing Tin, S.; Sène, D.; & Lefaucheur, J. P. (2019). "The clinical features of painful small‐fiber neuropathy suggesting an origin linked to primary Sjögren's syndrome". Pain Practice. 19 (4): 426–434. doi:10.1111/papr.12763. PMID 30636091. S2CID 58646701.
  22. ↑ Ng Wing Tin, S.; Zouari, H. G.; Wahab, A.; Sène, D.; & Lefaucheur, J. P. (2019). "Characterization of Neuropathic Pain in Primary Sjögren's Syndrome with Respect to Neurophysiological Evidence of Small-Fiber Neuropathy". Pain Medicine. 20 (5): 979–987. doi:10.1093/pm/pny183. PMID 30247738.
  23. 1 2 Fabry, V.; Gerdelat, A.; Acket, B.; Cintas, P.; Rousseau, V.; Uro-Coste, E.; ... & Traon, P. L. (2020). "Which Method for Diagnosing Small Fiber Neuropathy?". Frontiers in Neurology. 11: 342. doi:10.3389/fneur.2020.00342. PMC 7214721. PMID 32431663.
  24. ↑ Porubcin, M. G.; & Novak, P. (2020). "Diagnostic Accuracy of Electrochemical Skin Conductance in the Detection of Sudomotor Fiber Loss". Frontiers in Neurology. 11: 273. doi:10.3389/fneur.2020.00273. PMC 7212463. PMID 32425871.
  25. ↑ Yajnik, C. S.; Behere, R. V.; Bhat, D. S.; Memane, N.; Raut, D.; Ladkat, R.; ... & Fall, C. H. (2019). "A physiological dose of oral vitamin B-12 improves hematological, biochemical-metabolic indices and peripheral nerve function in B-12 deficient Indian adolescent women". PLOS ONE. 14 (10): e0223000. Bibcode:2019PLoSO..1423000Y. doi:10.1371/journal.pone.0223000. PMC 6786546. PMID 31600243. S2CID 204244441.
  26. ↑ Didangelos, T.; Karlafti, E.; Kotzakioulafi, E.; Margariti, E.; Giannoulaki, P.; Batanis, G.; ... & Kantartzis, K. (2021). "Vitamin B12 Supplementation in Diabetic Neuropathy: A 1-Year, Randomized, Double-Blind, Placebo-Controlled Trial". Nutrients. 13 (2): 395. doi:10.3390/nu13020395. PMC 7912007. PMID 33513879. S2CID 231762127.
  27. ↑ Syngle, A.; Chahal, S.; & Vohra, K. (2021). "Efficacy and tolerability of DPP4 inhibitor, teneligliptin, on autonomic and peripheral neuropathy in type 2 diabetes: an open label, pilot study". Neurological Sciences. 42 (4): 1429–1436. doi:10.1007/s10072-020-04681-2. PMID 32803534. S2CID 221129340.
  28. ↑ Casellini, C. M.; Parson, H. K.; Hodges, K.; Edwards, J. F.; Lieb, D. C.; Wohlgemuth, S. D.; & Vinik, A. I. (2016). "Bariatric surgery restores cardiac and sudomotor autonomic C-fiber dysfunction towards normal in obese subjects with type 2 diabetes". PLOS ONE. 11 (5): e0154211. Bibcode:2016PLoSO..1154211C. doi:10.1371/journal.pone.0154211. PMC 4854471. PMID 27137224.
  29. 1 2 Chizmadzhev, Y. A.; Indenbom, A. V.; Kuzmin, P. I.; Galichenko, S. V.; Weaver, J. C.; & Potts, R. O. (1998). "Electrical properties of skin at moderate voltages: contribution of appendageal macropores". Biophysical Journal. 74 (2): 843–856. Bibcode:1998BpJ....74..843C. doi:10.1016/S0006-3495(98)74008-1. PMC 1302564. PMID 9533696.
  30. ↑ Sato, K.; Kang, W. H.; Saga, K.; & Sato, K. T. (1989). "Biology of sweat glands and their disorders. I. Normal sweat gland function". Journal of the American Academy of Dermatology. 20 (4): 537–563. doi:10.1016/S0190-9622(89)70063-3. PMID 2654204.
  31. ↑ Tiwari, P.; Dwivedi, S.; Singh, M. P.; Mishra, R.; & Chandy, A. (2013). "Basic and modern concepts on cholinergic receptor: A review". Asian Pacific Journal of Tropical Disease. 3 (5): 413–420. doi:10.1016/S2222-1808(13)60094-8. PMC 4027320.
  32. ↑ Quinton, P. M. (1989). "Defective epithelial ion transport in cystic fibrosis". Clinical Chemistry. 35 (5): 726–730. doi:10.1093/clinchem/35.5.726. PMID 2655997.
  33. ↑ Sène, D. (2018). "Small fiber neuropathy: diagnosis, causes, and treatment". Joint Bone Spine. 85 (5): 553–559. doi:10.1016/j.jbspin.2017.11.002. PMID 29154979.
  34. ↑ Vinik, A. I.; Casellini, C.; Parson, H. K.; Colberg, S. R.; & Nevoret, M. L. (2018). "Cardiac autonomic neuropathy in diabetes: a predictor of cardiometabolic events". Frontiers in Neuroscience. 12: 591. doi:10.3389/fnins.2018.00591. PMC 6119724. PMID 30210276.
  35. ↑ Kucera, P.; Goldenberg, Z.; & Kurca, E. (2004). "Sympathetic skin response: review of the method and its clinical use". Bratislavske Lekarske Listy. 105 (3): 108–116. PMID 15253529.
  36. ↑ Berger, M. J.; & Kimpinski, K. (2013). "Test–retest reliability of quantitative sudomotor axon reflex testing". Journal of Clinical Neurophysiology. 30 (3): 308–312. doi:10.1097/WNP.0b013e3182873254. PMID 23733097. S2CID 35015328.
  37. ↑ Peltier, A.; Smith, A. G.; Russell, J. W.; Sheikh, K.; Bixby, B.; Howard, J.; ... & Singleton, J. R. (2009). "Reliability of quantitative sudomotor axon reflex testing and quantitative sensory testing in neuropathy of impaired glucose regulation". Muscle & Nerve. 39 (4): 529–535. doi:10.1002/mus.21210. PMC 4421877. PMID 19260066.
  38. ↑ Papanas, N.; Papatheodorou, K.; Christakidis, D.; Papazoglou, D.; Giassakis, G.; Piperidou, H.; ... & Maltezos, E. (2005). "Evaluation of a new indicator test for sudomotor function (Neuropad®) in the diagnosis of peripheral neuropathy in type 2 diabetic patients". Experimental and Clinical Endocrinology & Diabetes. 113 (4): 195–198. doi:10.1055/s-2005-837735. PMID 15891953.
This article is issued from Offline. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.