Sudomotor dysfunction in patients with gluten neuropathy

Abstract Background and aim Gluten neuropathy (GN) is a common neurological manifestation of gluten sensitivity (GS), characterized by serological evidence of GS, while other risk factors for developing neuropathy are absent. The degree of small fiber dysfunction in GN has not been studied in depth to date. Small fiber involvement may lead to pain, thermal perception abnormalities, and sweat gland dysfunction. Sudomotor innervation refers to the cholinergic innervation of the sympathetic nervous system through small fibers in the sweat glands. The aim of our study was to assess the sudomotor function of GN patients. Methods Patients with GN were recruited. Clinical and neurophysiological data were obtained. HLA-DQ genotyping was performed. The skin electrochemical conductance (ESC) was measured with SUDOSCANTM. Results Thirty-two patients (25 males, mean age 69.5±10.2 years) were recruited. Thirteen patients (40.6%) had abnormal sudomotor function of the hands. Sixteen patients (50%) had abnormal sudomotor function of the feet. Twenty-one patients (65.6%) had abnormal sudomotor function of either the hands or feet. Sudomotor dysfunction did not correlate with the type of neuropathy (length-dependent neuropathy or sensory ganglionopathy), gluten-free diet adherence, severity of neuropathy, and duration of disease or HLA-DQ genotype. No differences in the ESC were found between patients with painful and patients with painless GN. Conclusion Sudomotor dysfunction affects two-thirds of patients with GN. The lack of correlation between pain and sudomotor dysfunction suggests different patterns of small fiber involvement in patients with GN.

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Validation of a Brazilian quantitative sensory testing (QST) device for the diagnosis of small fiber neuropathies

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2011000700019 ◽

2011 ◽

Vol 69 (6) ◽

pp. 943-948 ◽

Cited By ~ 25

Author(s):

Pedro Schestatsky ◽

Luciana Cadore Stefani ◽

Paulo Roberto Sanches ◽

Danton Pereira da Silva Júnior ◽

Iraci Lucena Silva Torres ◽

...

Keyword(s):

Quantitative Sensory Testing ◽

Stimulus Change ◽

Heat Pain ◽

Thermal Perception ◽

Sensory Testing ◽

Brazilian Sample ◽

Small Fiber ◽

Normal Individuals ◽

Nociceptive Pathway

Quantitative sensory testing (QST) is defined as the determination of thresholds for sensory perception under controlled stimulus. Our aim was to validate a new QST device for Brazilian sample. In 20 healthy adults, thermoalgesic thresholds were assessed using a QST prototype (Heat Pain Stimulator-1.1.10; Brazil). A 30 × 30 mm² thermode with a 1°C/s stimulus change rate were applied. Thresholds of three consecutive stimuli were averaged in two different sessions separated by at least two weeks. Additionally long thermal heat pain stimulus was performed. To evaluate the consistency of our method we also analyzed 11 patients with small fiber neuropathy. Results showed good reproducibility of thermal perception thresholds in normal individuals and plausible abnormal thresholds in patients. We conclude that our QST device is reliable when analyzing the nociceptive pathway in controls and patients.

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Ross Syndrome: A Patient with a 23-Year History

Case Reports in Neurology ◽

10.1159/000507186 ◽

2020 ◽

Vol 12 (1) ◽

pp. 132-135

Author(s):

Zuhal Filikci ◽

Hans-Henrik Horsten ◽

Mette Lindelof

Keyword(s):

Careful Examination ◽

Sweat Glands ◽

Term Outcome ◽

Lower Quadrant ◽

Compensatory Hyperhidrosis ◽

Long Term Outcome ◽

Sudomotor Function ◽

Sympathetic Function ◽

Autonomic Testing ◽

A Minor

We present a 60-year-old female with a 23-year history of anhidrosis with concomitant heat intolerance. At examination, we found a right-sided tonic pupil, absent tendon reflexes, and a segmental patch of compensatory hyperhidrosis in the left lower quadrant of her trunk. To further confirm this finding, a minor test (a starch-iodine test, which is used to evaluate the sudomotor function, sweating) was performed. Nerve conduction studies revealed evidence of a mild distal sensory polyneuropathy of the axonal type. Tilt-table testing showed signs of orthostatic hypotension with evidence of reduced sympathetic function. Skin biopsy excluded pathology in the sweat glands. Our patient met the criteria for a diagnosis of Ross syndrome. This case describes the long-term outcome of this rare entity and highlights how careful examination and bedside autonomic testing can confirm the diagnosis of autonomic neurological disorders.

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Time in range, especially overnight time in range, is associated with sudomotor dysfunction in patients with type 1 diabetes

Diabetology & Metabolic Syndrome ◽

10.1186/s13098-021-00739-z ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Zhou-qin Feng ◽

Qing-yu Guo ◽

Wei Wang ◽

Yan-yu Yuan ◽

Xu-guang Jin ◽

...

Keyword(s):

Type 1 Diabetes ◽

Microvascular Complications ◽

Correlation Coefficients ◽

Sweat Glands ◽

Sudomotor Function ◽

Time In Range ◽

Logistic Regressions ◽

Independent Association ◽

The Relationship

Abstract Background Time in range (TIR) is advocated as key metric of glycemic control and is reported to be associated with microvascular complications of diabetes. Sudomotor dysfunction is among the earliest detectable diabetic peripheral neuropathy (DPN). We set about to research the relationship between TIR including overnight TIR and sudomotor function detected by SUDOSCAN with the intention of exploring the correlation of TIR including overnight TIR and early DPN in type 1 diabetes (T1D). Methods 95 patients with T1D were enrolled. TIR including nocturnal TIR of 3.9–10.0 mmol/L was evaluated with CGM. SUDOSCAN measured feet electrochemical skin conductance (FESC) and sudomotor dysfunction was defined as average FESC < 60µS. Logistic regressions were applied to examine the independent association of TIR and overnight TIR with sudomotor function. Results The overall prevalence of sudomotor dysfunction was 28.42%. Patients with sudomotor dysfunction had significantly lower TIR for the whole recorded phase and for nighttime. The sudomotor dysfunction prevalence progressively declined with the ascending tertiles of TIR and nocturnal TIR (P for trend < 0.05). Correlation analysis showed that the relationship between nocturnal TIR and FESC was stronger than that between TIR and FESC with correlation coefficients were respectively 0.362 and 0.356 (P < 0.001). Finally, logistic regression analysis indicated the independently negative relation between TIR and nocturnal TIR and sudomotor dysfunction (P < 0.05), and the correlation between nocturnal TIR and sudomotor dysfunction was more statistically significant. Conclusions TIR is negatively correlated with sudomotor dysfunction in T1D independent of HbA1c. Furthermore, decreased nocturnal TIR is more closely related to the impaired function of sudomotor nerves in sweat glands.

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Influence of isometric exercise on blood flow and sweating in glabrous and nonglabrous human skin

Journal of Applied Physiology ◽

10.1152/jappl.2001.91.6.2487 ◽

2001 ◽

Vol 91 (6) ◽

pp. 2487-2492 ◽

Cited By ~ 41

Author(s):

Adham R. Saad ◽

Dan P. Stephens ◽

Lee Ann T. Bennett ◽

Nisha Charkoudian ◽

Wojciech A. Kosiba ◽

...

Keyword(s):

Blood Flow ◽

Sweat Rate ◽

Isometric Exercise ◽

Sweat Glands ◽

Isometric Handgrip ◽

Doppler Flowmetry ◽

Leg Extension ◽

Sudomotor Function ◽

Large Fluctuations ◽

Leg Exercise

The distribution of the reflex effects of isometric exercise on cutaneous vasomotor and sudomotor function is not clear. We examined the effects of isometric exercise by different muscle masses on skin blood flow (SkBF) and sweat rate (SR) in nonglabrous skin and in glabrous skin. The latter contains arteriovenous anastomoses (AVAs), which cause large fluctuations in SkBF. SkBF was measured by laser-Doppler flowmetry (LDF) and reported as cutaneous vascular conductance (CVC; LDF/mean arterial pressure). SR was measured by capacitance hygrometry. LDF and SR were measured at the sole, palm, forearm, and ventral leg during separate bouts of isometric handgrip (IHG) and isometric leg extension (ILE). CVC and its standard deviation decreased significantly during IHG and ILE in the palm and sole ( P < 0.05) but not in the forearm or leg ( P > 0.05). Only palmar SR increased significantly during IHG and ILE ( P < 0.05). We conclude that the major reflex influences of isometric exercise on the skin include AVAs and palmar sweat glands and that this is true for both arm and leg exercise.

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Sudomotor Dysfunction

Seminars in Neurology ◽

10.1055/s-0040-1713847 ◽

2020 ◽

Vol 40 (05) ◽

pp. 560-568

Author(s):

William P. Cheshire

Keyword(s):

Diagnostic Marker ◽

Heat Stroke ◽

Sympathetic Skin Response ◽

Sweat Test ◽

Axon Reflex ◽

Sudomotor Function ◽

Small Fiber ◽

Skin Response ◽

Patient At Risk ◽

Thermoregulatory Sweat Test

AbstractDisorders of sudomotor function are common and diverse in their presentations. Hyperhidrosis or hypohidrosis in generalized or regional neuroanatomical patterns can provide clues to neurologic localization and inform neurologic diagnosis. Conditions that impair sudomotor function include small fiber peripheral neuropathy, sudomotor neuropathy, myelopathy, α-synucleinopathies, autoimmune autonomic ganglionopathy, antibody-mediated hyperexcitability syndromes, and a host of medications. Particularly relevant to neurologic practice is the detection of postganglionic sudomotor deficits as a diagnostic marker of small fiber neuropathies. Extensive anhidrosis is important to recognize, as it not only correlates with symptoms of heat intolerance but may also place the patient at risk for heat stroke when under conditions of heat stress. Methods for assessing sudomotor dysfunction include the thermoregulatory sweat test, the quantitative sudomotor axon reflex test, silicone impressions, and the sympathetic skin response.

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Pilocarpine-induced sweat gland function in individuals with multiple sclerosis

Journal of Applied Physiology ◽

10.1152/japplphysiol.00860.2004 ◽

2005 ◽

Vol 98 (5) ◽

pp. 1740-1744 ◽

Cited By ~ 31

Author(s):

Scott L. Davis ◽

Thad E. Wilson ◽

Jamie M. Vener ◽

Craig G. Crandall ◽

Jack H. Petajan ◽

...

Keyword(s):

Multiple Sclerosis ◽

Exercise Training ◽

Sweat Gland ◽

Aerobic Training ◽

Sweat Rate ◽

Aerobic Exercise Training ◽

Sweat Glands ◽

Sudomotor Function ◽

Sweat Function ◽

Gland Function

This investigation tested the hypothesis that cholinergic sweat function of individuals with multiple sclerosis (MS) (MS-Con; n = 10) is diminished relative to matched healthy control subjects (Con; n = 10). In addition, cholinergic sweat function was determined before and after 15 wk of aerobic training in a subgroup of individuals with MS (MS-Ex; n = 7). Cholinergic sweating responses were assessed via pilocarpine iontophoresis on ventral forearm skin. A collection disk placed over the stimulated area collected sweat for 15 min. Sweat rate (SR) was calculated by dividing sweat collector volume by collection area and time. Iodine-treated paper was applied to the stimulated area to measure number of activated sweat glands (ASG). Sweat gland output (SGO) was calculated by dividing SR by density of glands under the collector. Sweat gland function was determined in MS-Ex to test the hypothesis that exercise training would increase sweating responses. No differences in ASG were observed between MS-Con and Con. SR and SGO in MS-Con [0.18 mg·cm−2·min−1 (SD 0.08); 1.74 μg·gland−1·min−1 (SD 0.79), respectively] were significantly lower ( P ≤ 0.05) than in Con [0.27 mg·cm−2·min−1 (SD 0.10); 2.43 μg·gland−1·min−1 (SD 0.69)]. Aerobic exercise training significantly ( P ≤ 0.05) increased peak aerobic capacity in MS-Ex [1.86 (SD 0.75) vs. 2.10 (SD 0.67) l/min] with no changes in ASG, SR, and SGO. Sweat gland function in individuals with MS is impaired relative to healthy controls. Fifteen weeks of aerobic training did not increase stimulated sweating responses in individuals with MS. Diminished peripheral sweating responses may be a consequence of impairments in autonomic control of sudomotor function.

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The autonomic innervation of hairy skin in humans: an in vivo confocal study

Scientific Reports ◽

10.1038/s41598-019-53684-3 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 8

Author(s):

Vincenzo Donadio ◽

Alex Incensi ◽

Veria Vacchiano ◽

Rossella Infante ◽

Martina Magnani ◽

...

Keyword(s):

Autonomic Innervation ◽

Sensory Function ◽

Cholinergic Innervation ◽

Autonomic Nerve ◽

Sweat Glands ◽

Small Subset ◽

Hairy Skin ◽

Specific Distribution ◽

Adrenergic Fibers

AbstractThe autonomic innervation of the skin includes different subsets of adrenergic and cholinergic fibers both in humans and animals. The corresponding chemical code is complex and often difficult to ascertain. Accordingly, a detailed histochemical description of skin autonomic fiber subtypes is lacking in humans. To characterize skin autonomic nerve subtypes may help to better understand the selective damage of specific skin autonomic fibers affecting human diseases such as the adrenergic fibers directed to skin vessels in Parkinson’s disease or the cholinergic sudomotor fibers in Ross Syndrome. The present study aimed at characterizing subtypes of autonomic fibers in relation to their target organs by means of an immunofluorescent technique and confocal microscopy. We studied 8 healthy subjects (5 males and 3 females) aged 45 ± 2 (mean ± SE) years without predisposing causes for peripheral neuropathy or autonomic disorders. They underwent skin biopsy from proximal (thigh) and distal (leg) hairy skin. A combination of adrenergic (i.e. tyrosine-hydroxylase- TH and dopamine beta-hydroxylase- DbH) and cholinergic (vesicular acetylcholine transporter- VACHT) autonomic markers and neuropeptidergic (i.e. neuropeptide Y- NPY, calcitonin gene-related peptide- CGRP, substance P- SP, and vasoactive intestinal peptide- VIP) markers were used to characterize skin autonomic fibers. The analysed skin autonomic structures included: 58 sweat glands, 91 skin arterioles and 47 arrector pili muscles. Our results showed that all skin structures presented a sympathetic adrenergic but also cholinergic innervation although in different proportions. Sympathetic adrenergic fibers were particularly abundant around arterioles and arrector pili muscles whereas sympathetic cholinergic fibers were mainly found around sweat glands. Neuropeptides were differently expressed in sympathetic fibers: NPY were found in sympathetic adrenergic fibers around skin arterioles and very seldom sweat glands but not in adrenergic fibers of arrector pili muscles. By contrast CGRP, SP and VIP were expressed in sympathetic cholinergic fibers. Cholinergic fibers expressing CGRP, SP or VIP without TH or DbH staining were found in arterioles and arrector pili muscles and they likely represent parasympathetic fibers. In addition, all skin structures contained a small subset of neuropeptidergic fibers devoid of adrenergic and cholinergic markers with a likely sensory function. No major differences were found between males and females and proximal and distal sites. In summary hairy skin contains sympathetic adrenergic and cholinergic fibers differently distributed around skin structures with a specific distribution of neuropeptides. The autonomic skin innervation also contains a small amount of fibers, likely to be parasympathetic and sensory.

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Evaluation of sweating responses in patients with collagen disease using the quantitative sudomotor axon reflex test (QSART): a study protocol for an investigator-initiated, prospective, observational clinical study

BMJ Open ◽

10.1136/bmjopen-2021-050690 ◽

2021 ◽

Vol 11 (10) ◽

pp. e050690

Author(s):

Miwa Ashida ◽

Tomohiro Koga ◽

Shimpei Morimoto ◽

Mariko Yozaki ◽

Daisuke Ehara ◽

...

Keyword(s):

Raynaud’S Phenomenon ◽

Raynaud's Phenomenon ◽

University Hospital ◽

Cholinergic Innervation ◽

Collagen Disease ◽

Sweat Glands ◽

Research Review ◽

Digital Ulcers ◽

Axon Reflex ◽

Sweat Secretion

IntroductionSweat secretion is controlled by the sympathetic nervous system and is less active during winter than in the summer. Raynaud’s phenomenon is affected by an excessive strain of the sympathetic nerves after exposure to a cold environment, thus reducing the quality of life of patients with collagen disease. Herein, we focus on the eccrine sweat glands that receive both adrenergic and cholinergic innervation. Our hypothesis is that excessive activation of sympathetic nerve in Raynaud’s phenomenon can affect sweating, especially in winter. This study is designed to evaluate the neuroactive sweating responses in patients with collagen disease and to assess its association with skin findings in peripheral circulatory disorders.Methods and analysisThe study will be conducted at a single centre in Japan. Patients with systemic sclerosis, Sjogren’s syndrome, systemic lupus erythematosus, mixed connective tissue disease, and dermatomyositis will be assessed using the quantitative sudomotor axon reflex test. The primary outcomes will be sweat volume and reaction time due to axon reflex and the Raynaud’s condition score. The secondary outcomes will include patient background, skin symptoms (digital ulcers, pernio-like eruptions, subcutaneous calcifications, telangiectasia, nailfold capillary dilatation/bleeding and degree of skin sclerosis) and skin surface temperature. Evaluation will be done two times, during the summer and winter, allowing for the assessment of seasonal differences in sweating responses.Ethics and disseminationEthical approval of this study was certified by the clinical research review board of Nagasaki University Hospital (Reference number: CRB19-001). We will disseminate the findings of this study through peer-reviewed publications and conference presentations.Trial registration numberjRCTs072190009; pre-results.

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Time in Range, Especially Overnight Time in Range, Is Associated With Sudomotor Dysfunction in Patients With Type 1 Diabetes

10.21203/rs.3.rs-840376/v1 ◽

2021 ◽

Author(s):

Zhou-qin Feng ◽

Qing-yu Guo ◽

Wei Wang ◽

Yan-yu Yuan ◽

Xu-guang Jin ◽

...

Keyword(s):

Type 1 Diabetes ◽

Regression Analysis ◽

Sweat Glands ◽

Negative Relation ◽

Sudomotor Function ◽

Time In Range ◽

Logistic Regressions ◽

Independent Association ◽

The Relationship

Abstract Background: To research the relationship between time in range (TIR) including overnight TIR and sudomotor function detected by SUDOSCAN in type 1 diabetes (T1D).Methods: 95 patients with T1D were enrolled. TIR of 3.9-10.0 mmol/L was evaluated with CGM. SUDOSCAN measured feet electrochemical skin conductance (FESC) and sudomotor dysfunction was defined as average FESC<60µS. Logistic regressions were applied to examine the independent association of TIR and overnight TIR with sudomotor function.Results: The overall prevalence of sudomotor dysfunction was 28.42%. Patients with sudomotor dysfunction had significantly lower TIR for the whole recorded phase and for nighttime. The sudomotor dysfunction prevalence progressively declined with the ascending tertiles of TIR and nocturnal TIR (P for trend <0.05). Correlation analysis showed that the relationship between nocturnal TIR and FESC was stronger than that between TIR and FESC with correlation coefficient was respectively 0.362 and 0.356 (P <0.001). Finally, logistic regression analysis indicated the independently negative relation between TIR and nocturnal TIR and sudomotor dysfunction (P <0.05), notably, more statistically significant results were obtained between nocturnal TIR and sudomotor dysfunction. Conclusions: TIR is negatively correlated with sudomotor dysfunction in T1D independent of HbA1c. Furthermore, decreased nocturnal TIR is more closely related to the impaired function of sudomotor nerves in sweat glands.

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Assessment of cutaneous axon-reflex responses to evaluate functional integrity of autonomic small nerve fibers

Neurological Sciences ◽

10.1007/s10072-020-04293-w ◽

2020 ◽

Vol 41 (7) ◽

pp. 1685-1696 ◽

Cited By ~ 5

Author(s):

Mido M. Hijazi ◽

Sylvia J. Buchmann ◽

Annahita Sedghi ◽

Ben M. Illigens ◽

Heinz Reichmann ◽

...

Keyword(s):

Quantitative Analysis ◽

Nerve Fibers ◽

Laser Speckle ◽

Laser Doppler ◽

Axon Reflex ◽

Reflex Responses ◽

Sudomotor Function ◽

Functional Integrity ◽

Small Fiber ◽

Small Nerve

Abstract Cutaneous autonomic small nerve fibers encompass unmyelinated C-fibers and thinly myelinated Aδ-fibers, which innervate dermal vessels (vasomotor fibers), sweat glands (sudomotor fibers), and hair follicles (pilomotor fibers). Analysis of their integrity can capture early pathology in autonomic neuropathies such as diabetic autonomic neuropathy or peripheral nerve inflammation due to infectious and autoimmune diseases. Furthermore, intraneural deposition of alpha-synuclein in synucleinopathies such as Parkinson’s disease can lead to small fiber damage. Research indicated that detection and quantitative analysis of small fiber pathology might facilitate early diagnosis and initiation of treatment. While autonomic neuropathies show substantial etiopathogenetic heterogeneity, they have in common impaired functional integrity of small nerve fibers. This impairment can be evaluated by quantitative analysis of axonal responses to iontophoretic application of adrenergic or cholinergic agonists to the skin. The axon-reflex can be elicited in cholinergic sudomotor fibers to induce sweating and in cholinergic vasomotor fibers to induce vasodilation. Currently, only few techniques are available to quantify axon-reflex responses, the majority of which is limited by technical demands or lack of validated analysis protocols. Function of vasomotor small fibers can be analyzed using laser Doppler flowmetry, laser Doppler imaging, and laser speckle contrast imaging. Sudomotor function can be assessed using quantitative sudomotor axon-reflex test, silicone imprints, and quantitative direct and indirect testing of sudomotor function. More recent advancements include analysis of piloerection (goose bumps) following stimulation of adrenergic small fibers using pilomotor axon-reflex test. We provide a review of the current literature on axon-reflex tests in cutaneous autonomic small fibers.

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