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Martin Schmelz - One of the best experts on this subject based on the ideXlab platform.
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Electrically Stimulated Axon Reflexes Are Diminished in Diabetic Small Fiber Neuropathies
2016Co-Authors: Heidrun H. Krämer, Frank Birklein, Martin Schmelz, Andreas BickelAbstract:Axon Reflex mediated flare depends on the density and the function of cutaneous C-fibers and may be impaired in diabetic neuropathy. We induced neurogenic Axon Reflex flare by intracutaneous electrical stimulation and analyzed size and intensity of the flare on the dorsum of the foot and ventral thigh with laser Doppler imaging (LDI). We investigated 12 diabetic subjects with small fiber neuropathies (SFNs), 5 diabetic subjects without neuropathy (NO-Ns), and 14 healthy control subjects. Five of the normal subjects were reassessed after 12 months. In comparing patients with SFN to control subjects, we found that SFN flare size but not the intensity of vasodilation (flux) was reduced on the feet (P < 0.001) and thighs (P < 0.007). Furthermore, elec-trical thresholds for flare induction were increase
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objective assessment of c fiber function by electrically induced Axon Reflex flare in patients with Axonal and demyelinating polyneuropathy
Journal of Clinical Neurophysiology, 2013Co-Authors: Panagiotis Kokotis, Martin Schmelz, Aikaterini Papagianni, Thomas Zambelis, Nikos KarandreasAbstract:INTRODUCTION A simple test to evaluate the peripheral C-fiber function is the measurement of Axon Reflex flare area. In this study, we compared the flare area in healthy subjects and in two groups of patients with predominantly Axonal or demyelinating polyneuropathy. MATERIALS AND METHODS We examined 42 control subjects and 33 patients. The flare responses were elicited by the application of transcutaneous electrical stimulation and recorded by laser Doppler imaging. RESULTS There was a significant reduction of electrically induced flare area in both groups of neuropathy patients (P < 0.001; analysis of covariance). Interestingly, patients with an Axonal neuropathy had a significantly stronger reduction of flare size as compared to patients with demyelinating neuropathy (P = 0.03). CONCLUSIONS The evaluation of the Axon flare response in the arm can be used as a screening test of impaired C-fiber function in polyneuropathy patients with the advantages of simplicity of the procedure and time economy.
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Axon Reflex flare and quantitative sudomotor Axon Reflex contribute in the diagnosis of small fiber neuropathy
Muscle & Nerve, 2013Co-Authors: Barbara Namer, Martin Schmelz, Stefan Pfeffer, Hermann O Handwerker, Andreas BickelAbstract:Introduction Objective diagnosis of small fiber impairment is difficult. Methods We used the quantitative sudomotor Axon Reflex test (QSART) and Axon-Reflex-flare-test in the foot and thigh of 46 patients with peripheral neuropathy to assess C-fiber function in addition to conventional neurography and thermal threshold testing. Results In all patients, small fiber impairment was suspected because of abnormal warmth detection thresholds (76% of all tested) and/or pain in the feet. A total of 83% had reduced Axon-Reflex flare areas and 17% lower QSART scores. Patients with pure small fiber neuropathy had higher rates of reduced flare areas (87.5%) and sweating rates (25.5%). There was no difference between patients with and without pain regarding thermotesting and Axon-Reflex testing. Conclusions Both Axon-Reflex tests are helpful to identify objectively patients with small fiber impairment. Afferent and efferent C-fiber classes can be impaired differently. These tests detect small fiber impairment, but they cannot differentiate between painful and nonpainful neuropathy. Muscle Nerve 47: 357–363, 2013
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ngf enhances electrically induced pain but not Axon Reflex sweating
Pain, 2011Co-Authors: Otilia Obreja, Martin Schmelz, Olga Kluschina, Marcus Schley, Alexandra Mayer, Michael Hirth, Roman RukwiedAbstract:Abstract High-affinity receptors for nerve growth factor (NGF) are found on nociceptors and sympathetic efferents. NGF is known to sensitize nociceptors, increase innervation density, and fire frequency of sympathetic fibers. We explored Axonal sensitization of afferent and efferent fibers following intracutaneous injection of NGF in human and pig skin. In humans, frequency-dependent (5, 20, 100 Hz) electrically induced pain was assessed 1, 3, 7, 21, and 49 days post injection. Sweat output was recorded in parallel using the quantitative sudomotor Axon Reflex test (QSART). Electrically induced pain ratings (7.5 mA for 30 s) significantly increased at the NGF sites for 5 Hz (numeric rating scale [NRS] 6 ± 0.5 vs 3.7 ± 0.4), 20 Hz (NRS 7.2 ± 0.4 vs 5 ± 0.5), and 100 Hz stimulation (NRS 6.9 ± 0.4 vs 5.4 ± 0.3) at day 21, and also for 5 Hz at day 49 (NRS 5.4 ± 0.4 vs 3.8 ± 0.3). Electrically evoked QSART increased frequency dependent, but was not altered by NGF throughout the entire observation period (average QSART at 5 Hz: 3 mL/h/m2, 20 Hz: 9 mL/h/m2, 100 Hz: 10 mL/h/m2). Similarly, NGF did not change the activity-dependent slowing of conduction of sympathetic efferents (6 ± 2% vs 5.1 ± 1.5%, for 3 minutes, 2 Hz) in pig single-fiber recordings. In parallel to the increased pain ratings recorded in humans, activity-dependent slowing of mechano-insensitive nociceptors was reduced by NGF (18.1 ± 2% vs 29 ± 1.4%). In summary, Axonal sensitization of nociceptors by NGF could underlie the hyperalgesia to electrical stimulation. Enhanced responses were limited to nociceptors, as no sensitization was found in sympathetic efferent neurons.
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time course of acetylcholine induced activation of sympathetic efferents matches Axon Reflex sweating in humans
Journal of The Peripheral Nervous System, 2011Co-Authors: Roland Schmidt, Christian Weidner, Martin SchmelzAbstract:Action potentials from postganglionic C-fibres were recorded in healthy volunteers by microneurography in the peroneal nerve. Their responsiveness to mechanical or heat stimuli or to sympathetic Reflex provocation tests was determined by transient slowing of conduction velocity following activation. Twenty units were classified as sympathetic efferent units. Acetylcholine (ACh) iontophoresis (10%, 1 mA, 1 min) inside their innervation territory activated 8 of 20 sympathetic fibres with a mean delay of 61 ± 12 s, peak response at 175 ± 38 s, and a duration of 240 ± 42 s, whereas iontophoresis of saline did not activate any of them. The time course of neuronal activation correlated with the Axon Reflex sweating measured by an evaporimeter in a separate session (delay 76 ± 9 s, peak at 195 ± 12 s, decline to 50% of peak 312 ± 25 s). No ACh-induced vasoconstriction was observed by laser Doppler scanning (n = 11) even after depletion of neuropeptides by chronic topical capsaicin treatment (n = 8). We conclude that ACh iontophoresis activates about half of the sympathetic fibres in human skin and provokes a corresponding Axon Reflex sweating. The absence of ACh-induced vasoconstriction even after the depletion of neuropeptides by capsaicin suggests that only sudomotor fibres, but not sympathetic vasoconstrictor fibres are activated by this stimulus.
Timo Siepmann - One of the best experts on this subject based on the ideXlab platform.
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Assessment of cutaneous Axon-Reflex responses to evaluate functional integrity of autonomic small nerve fibers
Neurological Sciences, 2020Co-Authors: Mido M. Hijazi, Sylvia J. Buchmann, Heinz Reichmann, Annahita Sedghi, Ben M. Illigens, Gabriele Schackert, Timo SiepmannAbstract: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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Cutaneous Autonomic Pilomotor Testing to Unveil the Role of Neuropathy Progression in Early Parkinson’s Disease (CAPTURE PD): Protocol for a Multicenter Study
Frontiers Media S.A., 2017Co-Authors: Timo Siepmann, Sylvia J. Buchmann, Marie Luise Kubasch, Alexandra Pintér, Leonie Stibal, Martin Arndt, Anne Sophie Kubasch, Ana Isabel PenzlinAbstract:BackgroundIn Parkinson’s disease (PD), alpha-synuclein accumulation in cutaneous autonomic pilomotor and sudomotor nerve fibers has been linked to autonomic nervous system disturbances even in the early stages of the disease. This study aims to assess the association between alpha-synuclein-mediated structural autonomic nerve fiber damage and function in PD, elucidate the role of neuropathy progression during the early disease stages, and test reproducibility and external validity of pilomotor function assessment using quantitative pilomotor Axon-Reflex test and sudomotor function via quantitative direct and indirect test of sudomotor function.Methods/designA prospective controlled study will be conducted at four study sites in Europe and the USA. Fifty-two male and female patients with idiopathic PD (Hoehn and Yahr 1–2) and 52 age- and sex-matched healthy controls will be recruited. Axon-Reflex-mediated pilomotor erection will be induced by iontophoresis of phenylephrine on the dorsal forearm. Silicone impressions of the response will be obtained, scanned, and quantified for pilomotor muscle impressions by number, impression size, and area of Axon-Reflex spread. Axon-Reflex-mediated sweating following acetylcholine iontophoresis will be quantified for number and size of droplets and Axon-Reflex spread. Sympathetic skin responses, autonomic and motor symptoms will be evaluated. Tests will be performed at baseline, after 2 weeks, 1, 2, and 3 years. Skin biopsies will be obtained at baseline and after 3 years and will be analyzed for nerve fiber density and alpha-synuclein accumulation.DiscussionWe anticipate that progression of autonomic nerve dysfunction assessed via pilomotor and sudomotor Axon-Reflex tests is related to progression of autonomic symptom severity and alpha-synuclein deposition. Potential applications of the techniques include interventional studies evaluating disease-modifying approaches and clinical assessment of autonomic dysfunction in patients with PD.Clinical trail registrationTRN NCT03043768
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laser doppler assessment of vasomotor Axon Reflex responsiveness to evaluate neurovascular function
Frontiers in Neurology, 2017Co-Authors: Marie Luise Kubasch, Sylvia J. Buchmann, Anne Sophie Kubasch, Ben Minwoo Illigens, Juliana Torres Pacheco, Kristian Barlinn, Timo SiepmannAbstract:The vasomotor Axon Reflex can be evoked in peripheral epidermal nociceptive C-fibers to induce local vasodilation. This neurogenic flare response is a measure of C-fiber functional integrity and therefore shows impairment in patients with small fiber neuropathy. Laser Doppler Flowmetry (LDF) and laser Doppler Imaging (LDI) are both techniques to analyse vasomotor small fiber function by quantifying the integrity of the vasomotor mediated Axon-Reflex. While LDF assesses the flare response following acetylcholine iontophoresis with temporal resolution at a single defined skin point, LDI records flare responses with spatial and temporal resolution, generating a two-dimensional map of superficial blood flow. LDF is characterized by a high intra- and interindividual measurement variability, which is smaller in LDI due to its spatial resolution. Nevertheless, LDI still lacks standardized methods for image analysis. Consequently, use of the technique currently remains on an experimental level. Here, we sought to review the current literature on laser Doppler assessment of vasomotor function and discuss potential future applications of established techniques as well as those that are still experimental.
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pilomotor function is impaired in patients with parkinson s disease a study of the adrenergic Axon Reflex response and autonomic functions
Parkinsonism & Related Disorders, 2016Co-Authors: Timo Siepmann, Ana Isabel Penzlin, Marie Luise Kubasch, Elka Frenz, Susan Goelz, Wagner Zago, Ingeborg Friehs, Miriam Wienecke, Matthias Lohle, Wiebke SchrempfAbstract:Abstract Introduction Autonomic nervous system disturbances including sweating abnormalities and cardiovascular symptoms are frequent in Parkinson's disease (PD) and often precede motor involvement. Cholinergic vasomotor and sudomotor skin nerves are impaired in patients with PD even at early disease stages. We hypothesized that adrenergic pilomotor nerve function is similarly impaired in early PD and might constitute a novel diagnostic target. Methods We conducted a study in 12 PD patients (HoehnY impression area: 10.8 ± 2.2 mm 2 vs. 24.8 ± 3.1 mm 2 , p 2 vs. 185.9 ± 10.8 mm 2 , p Conclusion Pilomotor function is impaired in early stages of PD. Pilomotor Axon-Reflex assessment might be useful in the investigation of disease related pathology and supplement other clinical markers of autonomic neuropathy in PD.
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Axon Reflex basierte nervenmessverfahren in der diagnostik autonomer neuropathie
Nervenarzt, 2014Co-Authors: Timo Siepmann, Ben Minwoo Illigens, Heinz Reichmann, Tjalf ZiemssenAbstract:Axon-Reflex-basierte funktionelle Messverfahren kutaner Nervenfasern werden in der Diagnostik autonomer Neuropathien angewendet. Sie umfassen quantitative Methoden zur Erfassung vasomotorischer und sudomotorischer Antwortreaktionen auf die iontophoretische Applikation von Acetylcholin. Die etablierten Axon-Reflex-Messverfahren „laser Doppler flowmetry“ (LDF) zur vasomotorischen und „quantitative sudomotor Axon-Reflex test“ (QSART) zur sudomotorischen Funktionsmessung sind durch hohen technischen Aufwand und interindividuelle Variabilitat limitiert. Sie bleiben daher in der Regel spezialisierten klinischen Zentren vorbehalten. Neue Axon-Reflex-basierte Verfahren zeichnen sich durch die Erfassung der Axonalen Antwortreaktionen mit zeitlicher und zweidimensionaler Auflosung aus. Diese umfassen den „laser Doppler imaging (LDI) Axon-Reflex flare area test“ zur vasomotorischen, den „quantitative direct and indirect test of sudomotor function“ (QDIRT) zur sudomotorischen Funktionsmessung sowie den „quantitative pilomotor Axon-Reflex test“ (QPART), ein Verfahren zur Messung der pilomotorischen Nervenfunktion mithilfe adrenerger Stimulation der Haut durch Phenylephriniontophorese. Die Effektivitat neuer Axon-Reflex-basierter Messverfahren in der Neuropathiediagnostik ist Gegenstand derzeitiger klinischer Prufung.
Andreas Bickel - One of the best experts on this subject based on the ideXlab platform.
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Electrically Stimulated Axon Reflexes Are Diminished in Diabetic Small Fiber Neuropathies
2016Co-Authors: Heidrun H. Krämer, Frank Birklein, Martin Schmelz, Andreas BickelAbstract:Axon Reflex mediated flare depends on the density and the function of cutaneous C-fibers and may be impaired in diabetic neuropathy. We induced neurogenic Axon Reflex flare by intracutaneous electrical stimulation and analyzed size and intensity of the flare on the dorsum of the foot and ventral thigh with laser Doppler imaging (LDI). We investigated 12 diabetic subjects with small fiber neuropathies (SFNs), 5 diabetic subjects without neuropathy (NO-Ns), and 14 healthy control subjects. Five of the normal subjects were reassessed after 12 months. In comparing patients with SFN to control subjects, we found that SFN flare size but not the intensity of vasodilation (flux) was reduced on the feet (P < 0.001) and thighs (P < 0.007). Furthermore, elec-trical thresholds for flare induction were increase
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Axon Reflex flare and quantitative sudomotor Axon Reflex contribute in the diagnosis of small fiber neuropathy
Muscle & Nerve, 2013Co-Authors: Barbara Namer, Martin Schmelz, Stefan Pfeffer, Hermann O Handwerker, Andreas BickelAbstract:Introduction Objective diagnosis of small fiber impairment is difficult. Methods We used the quantitative sudomotor Axon Reflex test (QSART) and Axon-Reflex-flare-test in the foot and thigh of 46 patients with peripheral neuropathy to assess C-fiber function in addition to conventional neurography and thermal threshold testing. Results In all patients, small fiber impairment was suspected because of abnormal warmth detection thresholds (76% of all tested) and/or pain in the feet. A total of 83% had reduced Axon-Reflex flare areas and 17% lower QSART scores. Patients with pure small fiber neuropathy had higher rates of reduced flare areas (87.5%) and sweating rates (25.5%). There was no difference between patients with and without pain regarding thermotesting and Axon-Reflex testing. Conclusions Both Axon-Reflex tests are helpful to identify objectively patients with small fiber impairment. Afferent and efferent C-fiber classes can be impaired differently. These tests detect small fiber impairment, but they cannot differentiate between painful and nonpainful neuropathy. Muscle Nerve 47: 357–363, 2013
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c fiber Axon Reflex flare size correlates with epidermal nerve fiber density in human skin biopsies
Journal of The Peripheral Nervous System, 2009Co-Authors: Andreas Bickel, Max J Hilz, Gisela Heyer, Christine Senger, Christian Maihoefner, Dieter Heuss, Barbara NamerAbstract:Abstract The size of the neurogenic Axon Reflex flare (ARFS) has been proposed to serve as a non-invasive measure of C-fiber neuropathies. This idea is based on the observation that ARFS is often reduced in patients with small-fiber neuropathies. In this study, we compared ARFS and electrically evoked Axon Reflex sweating with intraepidermal nerve fiber density (IENF) in patients with peripheral neuropathy in order to validate these methods against an objective standard method of diagnosing small-fiber neuropathy. ARFS was significantly correlated with IENF, while Axon Reflex sweating was not correlated to IENF. We conclude that measurement of ARFS is a potential objective non-invasive diagnostic tool for analysis of C-fiber function in patients with small-fiber neuropathies.
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sudomotor function in familial dysautonomia
Journal of Neurology Neurosurgery and Psychiatry, 2004Co-Authors: Andreas Bickel, Felicia B Axelrod, H Marthol, Martin Schmelz, Max J HilzAbstract:Background: Patients with familial dysautonomia (FD) manifest episodic hyperhidrosis despite the reduction of sudomotor fibres and sweat glands associated with this autonomic neuropathy. We assessed peripheral sudomotor nerve fibre and sweat gland function to determine if this symptom was due to peripheral denervation hypersensitivity. Methods: In 14 FD patients and 11 healthy controls, direct and Axon Reflex mediated sweat responses were determined by measuring transepidermal water loss (TEWL) after application of acetylcholine via a microdialysis membrane, a novel method to evaluate sudomotor function in neuropathy patients. Results were compared with data from conventional quantitative sudomotor Axon Reflex testing (QSART). Using microdialysis, interstitial fluid was analysed for plasma proteins to evaluate protein extravasation induced by acetylcholine as an additional parameter of C-fibre function. Results: Although reduced Axon Reflex sweating was expected in FD patients, neither direct or Axon Reflex mediated sweat responses, nor acetylcholine induced protein extravasation differed between control and patient groups. However, the baseline resting sweat rate was higher in FD patients than controls (p<0.05). TEWL and QSART test results correlated (r = 0.64, p = 0.01), proving the reliability of TEWL methodology in evaluating sudomotor function. Conclusion: The finding of normal direct and Axon Reflex mediated sweat output in FD patients supports our hypothesis that, in a disorder with severe sympathetic nerve fibre reduction, sudomotor fibres, but not the sweat gland itself, exhibit chemical hypersensitivity. This might explain excessive episodic hyperhidrosis in situations with increased central sympathetic outflow.
Phillip A. Low - One of the best experts on this subject based on the ideXlab platform.
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normative values for sudomotor Axon Reflex testing using qsweat p1 282
Neurology, 2015Co-Authors: David M Sletten, Andrew Grandinetti, Phillip A. Low, Stephen D Weigand, Tonette Gehrking, Jade A Gehrking, Wolfgang SingerAbstract:OBJECTIVE: To establish normative values for QSWEAT™ in a large volunteer cohort. BACKGROUND: The indirect sudomotor response to iontophoresis of acetylcholine provides valuable information about the integrity of postganglionic sudomotor fibers. This methodology has been used for many years as Quantitative Sudomotor Axon Reflex Test (QSART) using proprietary equipment. A commercially available device (QSWEAT™) is now widely used in autonomic laboratories. Studies have shown that QSART- and QSWEAT™-derived sweat volumes - although strongly correlated - differ in magnitude. Previously reported normative values for QSART are therefore not suitable for QSWEAT™. DESIGN/METHODS: Over 400 healthy volunteers were recruited at the University of Hawaii and Mayo Clinic Rochester. All subjects underwent routine autonomic function testing using standardized environmental and skin temperature control. Acetylcholine (10[percnt] solution/gel) was iontophoresed into skin at four standardized sites. The evoked sweat response was measured using QSWEAT™ equipment. RESULTS: The sweat response distribution revealed increasing sweat volumes with age until a stable plateau was reached by age 20 with again decreasing sweat volumes beyond age 70. We therefore combined the data of subjects between ages 20 and 69 years for percentile calculations of adult normative values. Data of the young (≤19) and elderly (蠅70) were analyzed separately. 376 volunteers fell in the age range 20-69 years (men=148, women=228). Sweat volumes were significantly lower in women, but there was no significant difference by study site. The 5th percentiles of normal in the adult age range were (female/male): Forearm: 0.08/0.25; Proximal Leg: 0.19/0.48; Distal Leg: 0.14/0.62; Foot: 0.07/0.15mcl. CONCLUSIONS: We present normative values and suggested cut-offs of normal for sudomotor testing using QSWEAT™. Sweat volumes plateaued between ages 20-69, and were as expected markedly lower in women. Inspite of climate and racial differences, sweat volumes were not different between study sites. Supported by NIH (P01NS44233, U54NS065736, K23NS075141, UL1RR24150), Mayo Funds. Disclosure: Dr. Sletten has nothing to disclose. Dr. Grandinetti has nothing to disclose. Dr. Weigand has nothing to disclose. Dr. Gehrking has nothing to disclose. Dr. Gehrking has nothing to disclose. Dr. Low has received personal compensation for activities with Chelsea Therapeutics, Pfizer Inc., and WR Medical Electronics Company as a consultant. Dr. Singer has received license fee payments from Jacobus Pharmaceutical.
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Quantitative Sudomotor Axon Reflex Test (QSART)
Encyclopedia of the Neurological Sciences, 2014Co-Authors: Phillip A. LowAbstract:The Quantitative Sudomotor Axon Reflex Test is a quantitative test of postganglionic sudomotor function. The neural pathway is nicotinic and the sweat gland receptor is muscarinic. Stimulus consists of iontophoresed acetylcholine and evoked sweat volume is quantitated. The test is sensitive and reproducible in detecting denervation. Recording sites are over the arm and leg. There is extensive experience with the test in diabetic and other autonomic neuropathies, and in clinical trials.
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a novel gel based vehicle for the delivery of acetylcholine in quantitative sudomotor Axon Reflex testing
Autonomic Neuroscience: Basic and Clinical, 2009Co-Authors: David M Sletten, Kurt Kimpinski, Stephen D Weigand, Phillip A. LowAbstract:This study describes a novel gel based vehicle for the delivery of acetylcholine (ACh) during quantitative sudomotor Axon Reflex testing (QSART). A dose and current response study were undertaken on 20 healthy control participants to characterize the efficiency of a gel based vehicle for the delivery of ACh. Values obtained for total sweat volume and latency to sweat onset with gel iontophoresis of ACh during QSART were comparable to previously published normative data using solution based vehicles. Patient discomfort, utilizing the gel based vehicle during the QSART procedure, was minimal. Improvement in iontophoresis using the gel formulation as a vehicle for ACh delivery has the potential to lower the voltage required to overcome skin resistance during QSART and may result in improved patient comfort during the procedure.
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relationship of q sweat to quantitative sudomotor Axon Reflex test qsart volumes
Muscle & Nerve, 2009Co-Authors: David M Sletten, Stephen D Weigand, Phillip A. LowAbstract:Q-Sweat, a commercial quantitative sweat measurement system, is modeled on quantitative sudomotor Axon Reflex testing (QSART). This study investigated the sweat response using Q-Sweat and Mayo-QSART recordings under identical conditions in healthy normal controls. Ninety-four participants were recruited for this study. All participants underwent randomized bilateral QSART recordings over the four standard recording regions. For both men and women, Wilcoxon signed rank tests of paired differences showed significantly lower volumes at each of the four sites for Q-Sweat vs. Mayo-QSART. Linear regression analysis was used to estimate the relationship between Q-Sweat and Mayo-QSART volume measurements separately for men and women. Although there was variability about the regression lines, these fitted models can be used to estimate the expected Mayo-QSART volume given an observed Q-Sweat volume, although it is preferable to use the Q-Sweat normative database directly. We hypothesize that the constant-current generator used in conjunction with Q-Sweat provides a less efficient iontophoresis of acetylcholine than the Mayo-constructed constant-current stimulator and results in lower volumes.
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comparison of directly stimulated with Axon Reflex mediated sudomotor responses in human subjects and in patients with diabetes
Muscle & Nerve, 1993Co-Authors: Mikihiro Kihara, Tonette L Opfergehrking, Phillip A. LowAbstract:The muscarinic receptors of human eccrine sweat gland may be directly stimulated by iontophoresis of acetylcholine (direct response; DIR) and indirectly via nicotinic receptors and an Axon "Reflex" (AXR). Using a specially designed multicompartmental sweat cell and dual sudorometers, we were able to simultaneously record the evoked DIR and AXR responses. On a second day, we repeated the experiment under identical ambient and stimulus conditions but instead obtained silastic imprints of DIR and AXR for morphometry. Studies were done on 24 controls (mean +/- SD = 47.6 +/- 15.1 years) and 23 diabetic subjects (mean +/- SD = 49.6 +/- 16.3 years). In control subjects, sudorometric DIR recordings were consistently larger than AXR. There was no difference in sweat droplet density by sex, but the size of droplets was larger in males. In diabetic patients 3 of 23 had absent AXR but preserved DIR, suggesting that failure of AXR preceded DIR in patients with neuropathy. Patients with mild neuropathy had an overrepresentation of large diameter droplets in the silastic imprints of both DIR and AXR, while patients with severe neuropathy had a markedly reduced density and small diameter droplets.
Hermann O Handwerker - One of the best experts on this subject based on the ideXlab platform.
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Axon Reflex flare and quantitative sudomotor Axon Reflex contribute in the diagnosis of small fiber neuropathy
Muscle & Nerve, 2013Co-Authors: Barbara Namer, Martin Schmelz, Stefan Pfeffer, Hermann O Handwerker, Andreas BickelAbstract:Introduction Objective diagnosis of small fiber impairment is difficult. Methods We used the quantitative sudomotor Axon Reflex test (QSART) and Axon-Reflex-flare-test in the foot and thigh of 46 patients with peripheral neuropathy to assess C-fiber function in addition to conventional neurography and thermal threshold testing. Results In all patients, small fiber impairment was suspected because of abnormal warmth detection thresholds (76% of all tested) and/or pain in the feet. A total of 83% had reduced Axon-Reflex flare areas and 17% lower QSART scores. Patients with pure small fiber neuropathy had higher rates of reduced flare areas (87.5%) and sweating rates (25.5%). There was no difference between patients with and without pain regarding thermotesting and Axon-Reflex testing. Conclusions Both Axon-Reflex tests are helpful to identify objectively patients with small fiber impairment. Afferent and efferent C-fiber classes can be impaired differently. These tests detect small fiber impairment, but they cannot differentiate between painful and nonpainful neuropathy. Muscle Nerve 47: 357–363, 2013
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impact of scratching on itch and sympathetic Reflexes induced by cowhage mucuna pruriens and histamine
Acta Dermato-venereologica, 2009Co-Authors: Frauke Kosteletzky, Barbara Namer, Clemens Forster, Hermann O HandwerkerAbstract:Cowhage and histamine, both applied via spicules, were used to induce itch. The quality and intensity of the sensations, Axon Reflex flare, sympathetic skin vasoconstrictions and the interference of scratching with itch processing were studied. Axon Reflex flare reactions were measured by laser Doppler imaging and Reflex vasoconstrictions in the finger were recorded by laser Doppler flowmetry. Magnitude of itch sensations was assessed on an electronic visual analogue scale while the skin was intermittently scratched proximal to the application site. The quality of itch was assessed with a questionnaire. Only histamine produced an Axon Reflex flare. Histamine itch increased faster, but recovered more slowly after scratching, by which it was more effectively suppressed. Cowhage induced a sharper itch sensation and stronger vasoconstrictor Reflexes. These findings support the notion that both agents activate different pathways. The differences in sympathetic Reflex induction and in the modulation by scratching indicate differential central nervous processing.
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spatial extension of sudomotor Axon Reflex sweating in human skin
Journal of The Autonomic Nervous System, 1998Co-Authors: B Riedl, Frank Birklein, Mark Nischik, B Neundorfer, Hermann O HandwerkerAbstract:Acetylcholine (ACh) applied to human skin is known to elicit a sweat response, which consists of a direct muscarinergic (M3) activation of sweat glands and a nicotinic Axon Reflex response from sudomotor terminals. To visualize the extent of Axon Reflex sweating after ACh-iontophoresis, iodine starch staining was used. Iontophoresis was performed under occlusion at the peroneal aspects of the lower leg and the center of the foot dorsum of healthy volunteers (n = 10). Ten minutes after stimulation, the area of dark blue staining was recorded by a video camera. Control experiments were performed with saline, histamine, pilocarpine and nicotine iontophoresis. The stained area was measured and the maximum and minimum distance of its boundary from the edge of the iontophoresis probe was determined (maximum/minimum radius). Sizes of stained areas and maximum radii were significantly greater on the lower leg compared to the foot (P < 0.01). The median sizes of the stained areas on the leg were 14.6 cm2 and on the foot dorsum 8.0 cm2. The respective median maximum radii were 3.1 cm on the leg and 2.3 cm on the foot dorsum (median minimum, leg 1.1 cm, foot 0.8 cm). These results match microneurographic findings of innervation territories of sympathetic efferent units. Area sizes of stained skin showed a close correlation between both stimulation sites (R = 0.96, P < 0.01), i.e. the sizes of sweat responses on leg and foot show a constant relation (foot/leg = 0.57) in spite of their great interindividual variability. This novel technique of establishing sweat responses provides information on the size of sudomotor innervation territories and may be useful for clinical studies in patients with suspected impairment of sympathetic functions.
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stimulation of sudomotor Axon Reflex mechanism by carbachol in healthy subjects and patients suffering from diabetic polyneuropathy
Acta Neurologica Scandinavica, 1995Co-Authors: E Lang, B Neundorfer, A Spitzer, D Claus, Hermann O HandwerkerAbstract:Sudomotor Axon Reflex (SAR) mechanism was stimulated by percutaneous iontophoresis of carbachol in healthy subjects and patients suffering from diabetic polyneuropathy (PNP) of differing severity (stage I-III). SAR response was assessed by hygrometry and compared with histamine induced neurogenic vasodilatation (laser-Doppler flowmetry) and itching sensation (visual analogue scale), which may provide information on neuro-secretion and afferent function of nociceptive unmyelinated nerve fibers. Carbachol induced long lasting SAR response with maximal sweating rates 20–30 minutes after stimulus onset. In diabetic patients the carbachol induced SAR response and the histamine induced itching sensation were significantly reduced in stage III of PNP. In contrast, histamine induced vasodilatation was significantly impaired in all stages of PNP. It is concluded that prolonged SAR response following iontophoresis of carbachol can simplify evaluation of sudomotor function when compared to established tests using intradermal application of acetylcholine. Furthermore, to demonstrate impairment of unmyelinated nerve fibers in PNP, histamine induced vasodilatation was found to be more sensitive than SAR response.