Sudomotor function refers to the

autonomic nervous system The autonomic nervous system (ANS), sometimes called the visceral nervous system and formerly the vegetative nervous system, is a division of the nervous system that operates viscera, internal organs, smooth muscle and glands. The autonomic nervo ...

control of

sweat gland Sweat glands, also known as sudoriferous or sudoriparous glands, , are small tubular structures of the skin that produce sweat. Sweat glands are a type of exocrine gland, which are glands that produce and secrete substances onto an epithelial s ...

activity in response to various environmental and individual factors.

Sweat Perspiration, also known as sweat, is the fluid secreted by sweat glands in the skin of mammals. Two types of sweat glands can be found in humans: eccrine glands and Apocrine sweat gland, apocrine glands. The eccrine sweat glands are distribu ...

production is a vital thermoregulatory mechanism used by the body to prevent heat-related

illness A disease is a particular abnormal condition that adversely affects the structure or function (biology), function of all or part of an organism and is not immediately due to any external injury. Diseases are often known to be medical condi ...

as the

evaporation Evaporation is a type of vaporization that occurs on the Interface (chemistry), surface of a liquid as it changes into the gas phase. A high concentration of the evaporating substance in the surrounding gas significantly slows down evapora ...

of sweat is the body’s most effective method of heat reduction and the only

cooling Cooling is removal of heat, usually resulting in a lower temperature and/or Phase transition, phase change. Temperature lowering achieved by any other means may also be called cooling. The Heat transfer, transfer of Internal energy, thermal energ ...

method available when the air temperature rises above skin temperature. In addition, sweat plays key roles in grip, microbial defense, and

wound healing Wound healing refers to a living organism's replacement of destroyed or damaged tissue by newly produced tissue. In undamaged skin, the epidermis (surface, epithelial layer) and dermis (deeper, connective layer) form a protective barrier again ...

Physiology

Human

s are primarily classified as either eccrine or apocrine glands. Eccrine glands open directly onto the surface of the skin, while apocrine glands open into

hair follicle The hair follicle is an organ found in mammalian skin. It resides in the dermal layer of the skin and is made up of 20 different cell types, each with distinct functions. The hair follicle regulates hair growth via a complex interaction betwee ...

s. Eccrine glands are the predominant sweat gland in the human body with numbers totaling up to 4 million. They are located within the reticular dermal layer of the skin and distributed across nearly the entire surface of the body with the largest numbers occurring in the palms and soles. Eccrine sweat is secreted in response to both emotional and thermal stimulation. Eccrine glands are primarily innervated by small-diameter, unmyelinated class C-fibers from postganglionic sympathetic cholinergic neurons. Increases in body and skin temperature are detected by visceral and

peripheral A peripheral device, or simply peripheral, is an auxiliary hardware device that a computer uses to transfer information externally. A peripheral is a hardware component that is accessible to and controlled by a computer but is not a core compo ...

thermoreceptors, which send signals via class C and Aδ-fiber afferent somatic neurons through the lateral spinothalamic tract to the preoptic nucleus of the

hypothalamus The hypothalamus (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrin ...

for processing. In addition, there are warm-sensitive neurons located within the preoptic nucleus that detect increases in core body temperature. Efferent pathways then descend ipsilaterally from the hypothalamus through the

pons The pons (from Latin , "bridge") is part of the brainstem that in humans and other mammals, lies inferior to the midbrain, superior to the medulla oblongata and anterior to the cerebellum. The pons is also called the pons Varolii ("bridge of ...

and medulla to preganglionic sympathetic cholinergic neurons in the intermediolateral column of the

spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue that extends from the medulla oblongata in the lower brainstem to the lumbar region of the vertebral column (backbone) of vertebrate animals. The center of the spinal c ...

. The preganglionic neurons

synapse In the nervous system, a synapse is a structure that allows a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or a target effector cell. Synapses can be classified as either chemical or electrical, depending o ...

with postganglionic cholinergic sudomotor (and to a lesser extent

adrenergic Adrenergic means "working on adrenaline (epinephrine) or noradrenaline (norepinephrine)" (or on their receptors). When not further qualified, it is usually used in the sense of enhancing or mimicking the effects of epinephrine and norepinephrine ...

) neurons in the paravertebral sympathetic ganglia. When the action potential reaches the

axon An axon (from Greek ἄξων ''áxōn'', axis) or nerve fiber (or nerve fibre: see American and British English spelling differences#-re, -er, spelling differences) is a long, slender cellular extensions, projection of a nerve cell, or neuron, ...

terminal of the postganglionic neuron,

acetylcholine Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...

is released which binds and activates muscarinic M3 receptors on the basolateral membrane of the clear cells in the secretory coil of the eccrine gland. This triggers the release of intracellular

calcium Calcium is a chemical element; it has symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to it ...

storages and an influx of extracellular calcium which ultimately results in the movement of

chloride The term chloride refers to a compound or molecule that contains either a chlorine anion (), which is a negatively charged chlorine atom, or a non-charged chlorine atom covalently bonded to the rest of the molecule by a single bond (). The pr ...

ion (Cl⁻),

sodium Sodium is a chemical element; it has Symbol (chemistry), symbol Na (from Neo-Latin ) and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 element, group 1 of the peri ...

ion (Na⁺), and water into the duct lumen.

Dysfunction

Impaired sudomotor function can occur in any disorder that directly and/or indirectly affects the

, including

diabetes mellitus Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained hyperglycemia, high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or th ...

, amyloidosis, infections,

neurodegenerative diseases A neurodegenerative disease is caused by the progressive loss of neurons, in the process known as neurodegeneration. Neuronal damage may also ultimately result in their death. Neurodegenerative diseases include amyotrophic lateral sclerosis, mul ...

, multiple system

atrophy Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations (which can destroy the gene to build up the organ), malnutrition, poor nourishment, poor circulatory system, circulation, loss of hormone, ...

, and pure autonomic failure. Sudomotor dysfunction can manifest as increased or decreased sweating patterns. Both patterns have the potential to affect an individual’s quality of life. Excessive sweating can cause social embarrassment, while insufficient sweating can result in heat intolerance and dry skin. Depending on the severity of dyshidrosis, it may result in

hyperkeratosis Hyperkeratosis is thickening of the stratum corneum (the outermost layer of the epidermis, or skin), often associated with the presence of an abnormal quantity of keratin,Kumar, Vinay; Fausto, Nelso; Abbas, Abul (2004) ''Robbins & Cotran Pathol ...

, rhagades, ulcerations, and poor

due to altered epidermal moisturization. Sudomotor dysfunction is one of the most common and earliest neurophysiological manifestations of small fiber neuropathies. In some cases, it may be the only detectable neurologic manifestation. The

gold standard A gold standard is a backed currency, monetary system in which the standard economics, economic unit of account is based on a fixed quantity of gold. The gold standard was the basis for the international monetary system from the 1870s to the ...

for

diagnosis Diagnosis (: diagnoses) is the identification of the nature and cause of a certain phenomenon. Diagnosis is used in a lot of different academic discipline, disciplines, with variations in the use of logic, analytics, and experience, to determine " ...

of small fiber neuropathies is Intraepidermal Nerve Fiber Density (IENFD) measured from punch skin biopsies, but this procedure is invasive and inappropriate for long term follow-up. Sudomotor testing can be a valuable diagnostic tool for the early detection of small fiber neuropathies.

Assessment

There are several methods available for the assessment of sudomotor function. They vary in cost, technical complexity,

reproducibility Reproducibility, closely related to replicability and repeatability, is a major principle underpinning the scientific method. For the findings of a study to be reproducible means that results obtained by an experiment or an observational study or ...

, variability and the availability of normative data. However, it is important to note that all sudomotor function assessments are not specific for small fiber or sudomotor neuropathy, as they can also yield abnormal results from disorders of the sweat glands themselves. The following is a list of methods used in clinical practice and clinical research for sudomotor assessment. Thermoregulatory Sweat Test (TST) and Quantitative Sudomotor Axon Reflex Test (QSART) are considered the gold standards for assessment of sudomotor function. Newer methods may offer simpler, potentially more sensitive, and more widely available alternatives for screening and monitoring in the clinic of autonomic and small fiber neuropathies, particularly those associated with diabetes.

Thermoregulatory Sweat Test (TST)

The thermoregulatory sweat test (TST) was developed in the 1940s by Ludwig Guttmann to measure both preganglionic and postganglionic sudomotor function objectively. The test is performed in a standardized room with the temperature preheated to 45–50 °C and humidity set to 35–40%. The patient lies unclothed on an examination table. An indicator dye is evenly applied to the ventral surface of the patient’s skin excluding the eyes, ears, and perioral region. The dye changes color in response to a decrease in skin pH which occurs upon the onset of sweating as the room temperature is gradually raised. Pictures are taken to record the patient’s sweating patterns. In addition, a TST% is calculated by dividing the anhidrotic skin area by the total skin area and multiplying by 100. The TST% acts as an indicator of the severity of neurologic impairment. When used in conjunction with postganglionic sudomotor function testing, such as the quantitative sudomotor axon reflex test (QSART), it can differentiate a preganglionic lesion from a postganglionic lesion. A distal anhidrotic pattern is characteristic of length-dependent small fiber neuropathies, such as the distal symmetric polyneuropathy commonly seen in diabetic patients. The TST has proven to be a sensitive measure of sudomotor function. However, it is time-consuming and requires a highly specialized facility with trained personnel.

Quantitative Sudomotor Axon Reflex Test (QSART)

The quantitative sudomotor axon reflex test (QSART) was developed in 1983 by Phillip Low as a quantitative method for the identification of localized postganglionic sudomotor dysfunction. Three-compartment sweat capsules are placed on the forearm, proximal and distal leg, as well as the dorsum of the foot. The outer compartment of the capsule is filled with a 10%

solution, while nitrogen gas is released steadily onto the skin within the inner compartment. The middle compartment acts as a buffer between the inner and outer compartments to prevent direct stimulation of sweat glands or leakage of the acetylcholine solution. The outflow humidity of the nitrogen gas after passing across the skin is measured by a

hygrometer A hair tension dial hygrometer with a nonlinear scale. A hygrometer is an instrument that measures humidity: that is, how much water vapor is present. Humidity measurement instruments usually rely on measurements of some other quantities, such a ...

. Once a stable baseline of outflow humidity is reached, iontophoresis of the acetylcholine fluid is initiated by using a 2mA

electric current An electric current is a flow of charged particles, such as electrons or ions, moving through an electrical conductor or space. It is defined as the net rate of flow of electric charge through a surface. The moving particles are called charge c ...

to deliver the acetylcholine into the dermal skin layers. The acetylcholine binds to sweat glands (direct sweat response), and nicotinic and muscarinic receptors on the sudomotor nerve terminals, which transmit the action potential antidromically to axon branch points and then orthodromically to adjacent sudomotor nerves and glands (indirect sweat response). Sweat production is measured as the change in relative humidity over time. The temporal resolution, magnitude, and onset latency of the sweat response are digitally recorded and analyzed using specialized software. QSART is sensitive and specific for detecting postganglionic small fiber dysfunction. However, some studies have found it to have a high variability, poor

, and low diagnostic sensitivity. It is also sensitive to various factors such as caffeine and medications, and the iontophoresis procedure may cause skin irritation and discomfort. QSART requires highly specialized equipment needing regular calibration, a humidity- and temperature-controlled room, and trained personnel.

Electrochemical Skin Conductance (ESC) - Sudoscan

Electrochemical skin conductance is an objective, quantitative, non-invasive method for the assessment of sudomotor function that utilizes chronoamperometry (the application of rectangular

direct current Direct current (DC) is one-directional electric current, flow of electric charge. An electrochemical cell is a prime example of DC power. Direct current may flow through a conductor (material), conductor such as a wire, but can also flow throug ...

(DC) pulses of varying

voltage Voltage, also known as (electrical) potential difference, electric pressure, or electric tension, is the difference in electric potential between two points. In a Electrostatics, static electric field, it corresponds to the Work (electrical), ...

amplitudes) to electrically stimulate eccrine sweat glands, and reverse iontophoresis (the migration of

electrolyte An electrolyte is a substance that conducts electricity through the movement of ions, but not through the movement of electrons. This includes most soluble Salt (chemistry), salts, acids, and Base (chemistry), bases, dissolved in a polar solven ...

s from the human sweat to the

electrode An electrode is an electrical conductor used to make contact with a nonmetallic part of a circuit (e.g. a semiconductor, an electrolyte, a vacuum or a gas). In electrochemical cells, electrodes are essential parts that can consist of a varie ...

s) for quantitative measurement of the resulting flow of Cl- ions. Currently, ESC

measurement Measurement is the quantification of attributes of an object or event, which can be used to compare with other objects or events. In other words, measurement is a process of determining how large or small a physical quantity is as compared to ...

can be obtained with the use of a

medical device A medical device is any device intended to be used for medical purposes. Significant potential for hazards are inherent when using a device for medical purposes and thus medical devices must be proved safe and effective with reasonable assura ...

calle

Sudoscan. A novel Electrochemistry, electrochemical model of the skin was devised, reproducing the behavior of chloride ions and the properties of their

ion channel Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by Gating (electrophysiol ...

to develop a computational tool for measuring chloride ion flow through a sweat gland in response to an imposed voltage. ''In vitro'' electrochemical studies were then carried out in conventional three-electrode cells to identify the origin of currents measured upon the application of low voltage potentials with variable amplitudes to

stainless steel Stainless steel, also known as inox, corrosion-resistant steel (CRES), or rustless steel, is an iron-based alloy that contains chromium, making it resistant to rust and corrosion. Stainless steel's resistance to corrosion comes from its chromi ...

electrodes applied to the skin during clinical tests. These studies also evaluated the influence of different parameters in sweat (e.g.,

urea Urea, also called carbamide (because it is a diamide of carbonic acid), is an organic compound with chemical formula . This amide has two Amine, amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest am ...

, lactate) on the obtained currents. These studies formed the basis for the ESC methodology of measuring sudomotor function. The flow of Cl⁻ ions in the sweat secreted from the activated sweat glands are captured by the anode. This process is repeated twice for the feet and twice for the hands with the right and left electrodes alternating as the

anode An anode usually is an electrode of a polarized electrical device through which conventional current enters the device. This contrasts with a cathode, which is usually an electrode of the device through which conventional current leaves the devic ...

and

cathode A cathode is the electrode from which a conventional current leaves a polarized electrical device such as a lead-acid battery. This definition can be recalled by using the mnemonic ''CCD'' for ''Cathode Current Departs''. Conventional curren ...

. A conductance deduced from the resulting current between the electrodes and the voltages is reported as ESC, measured in microsiemens (μS), and is proportional to the Cl⁻ flow to the skin surface, that is to say the

ability Abilities are powers an agent has to perform various Action (philosophy), actions. They include common abilities, like walking, and rare abilities, like performing a double backflip. Abilities are intelligent powers: they are guided by the person ...

to secrete Cl⁻ ions by eccrine glands, thus providing a quantitative measurement of sudomotor function. The measurement requires no specific patient preparation or medical personnel training. The test lasts less than 3 minutes, and is innocuous and non-invasive. In general, decreased ESC values indicate a higher risk of sudomotor dysfunction, and thus a greater

likelihood A likelihood function (often simply called the likelihood) measures how well a statistical model explains observed data by calculating the probability of seeing that data under different parameter values of the model. It is constructed from the j ...

of small fiber neuropathy. Sudoscan has been shown to be useful in the detection of small fiber neuropathy in patients with and without type 2 diabetes mellitus (T2DM) with a sensitivity of 77 to 87% and a specificity of 67 to 92%, as well as in the screening of diabetic nephropathy. Sudoscan has been compared with other reference tests including Heart Rate Variability (HRV) indices, intraepidermal nerve fiber density, sweat gland nerve fiber density and quantitative sudomotor axon reflex testing (QSART). In addition to diabetes, low ESC values have been reported in association with increased severity of diabetic

kidney disease Kidney disease, or renal disease, technically referred to as nephropathy, is damage to or disease of a kidney. Nephritis is an Inflammation, inflammatory kidney disease and has several types according to the location of the inflammation. Infla ...

and

metabolic syndrome Metabolic syndrome is a clustering of at least three of the following five medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL). Metabolic syndro ...

. It has also been shown to be sensitive to change after different interventions in subjects with T2DM. ESC measurements are highly reproducible. Studies have shown ESC values to be dependent on

ethnicity An ethnicity or ethnic group is a group of people with shared attributes, which they Collective consciousness, collectively believe to have, and long-term endogamy. Ethnicities share attributes like language, culture, common sets of ancestry, ...

. For that purpose, normative reference values have been established on a total of 1,350

health Health has a variety of definitions, which have been used for different purposes over time. In general, it refers to physical and emotional well-being, especially that associated with normal functioning of the human body, absent of disease, p ...

y participants. Normative ESC values have also been established for pediatric age groups, and it has been demonstrated that ESC values begin to decrease in the eighth decade of life. ESC has the potential to be a useful tool for detecting small fiber neuropathies. It is highly sensitive, rapid, more accessible and less technically complex than current gold standard sudomotor function tests, and causes minimal-to-no patient discomfort, so very suitable for routine use.

Neuropad

Neuropad utilizes an adhesive pad with a

cobalt Cobalt is a chemical element; it has Symbol (chemistry), symbol Co and atomic number 27. As with nickel, cobalt is found in the Earth's crust only in a chemically combined form, save for small deposits found in alloys of natural meteoric iron. ...

(II) salt indicator that changes color from blue to pink in the presence of

moisture Moisture is the presence of a liquid, especially water, often in trace amounts. Moisture is defined as water in the adsorbed or absorbed phase. Small amounts of water may be found, for example, in the air (humidity), in foods, and in some comme ...

due to the hydration of cobalt ions. One pad is applied to the plantar surface of each foot in between the 1st and 2nd metatarsal heads. The pad is kept on each foot for ten minutes and the final color is recorded. A full change in color from blue to pink is considered a normal sweat response, while an absent or incomplete color change is considered abnormal. The strengths of Neuropad are its high sensitivity,

cost-effectiveness Cost-effectiveness analysis (CEA) is a form of economic analysis that compares the relative costs and outcomes (effects) of different courses of action. Cost-effectiveness analysis is distinct from cost–benefit analysis, which assigns a moneta ...

, and its potential as an at-home test. However, Neuropad has lower specificity, is not recommended for children and patients over the age of 70, and is sensitive to certain medications.

Silicone Imprint Method

Like QSART,

silicone In Organosilicon chemistry, organosilicon and polymer chemistry, a silicone or polysiloxane is a polymer composed of repeating units of siloxane (, where R = Organyl group, organic group). They are typically colorless oils or elastomer, rubber ...

imprint utilizes the principles of iontophoresis to measure the axon-reflex sweat response; however, unlike QSART, it allows for spatial but not temporal resolution of the sweat response. Following iontophoresis of a cholinergic agonist, a thin layer of silicone is applied to the tested skin area until

polymerization In polymer chemistry, polymerization (American English), or polymerisation (British English), is a process of reacting monomer molecules together in a chemical reaction to form polymer chains or three-dimensional networks. There are many fo ...

is complete (about 5 minutes). The silicone imprints are then analyzed, either by

microscope A microscope () is a laboratory equipment, laboratory instrument used to examine objects that are too small to be seen by the naked eye. Microscopy is the science of investigating small objects and structures using a microscope. Microscopic ...

or computer-assisted analysis, for sweat droplet size, number, and distribution, and compared to lower limits of normal. The silicone imprint method is relatively inexpensive and can be performed in non-specialized testing centers; however, the method is prone to artifacts caused by residual hair and dirt, as well as skin surface texture and air bubble formation; the accuracy of the results depends on the silicone material used; the processing of the sweat impressions is time consuming; and the technique requires

standardization Standardization (American English) or standardisation (British English) is the process of implementing and developing technical standards based on the consensus of different parties that include firms, users, interest groups, standards organiza ...

Quantitative Direct and Indirect Test (QDIRT)

The QDIRT was developed in 2008 by Christopher Gibbons and colleagues as a means for the evaluation of postganglionic sudomotor function outside of specialized autonomic testing centers. It combines elements of TST, QSART, and the silicone imprint method. Similar to QSART, it involves the iontophoresis of 10%

solution to induce axon-reflex sweating; however, it utilizes an automated imaging analysis software that is less technically complex. Prior to iontophoresis, the skin is dried and covered with an indicator dye consisting of povidone-iodine mixed with

corn starch Cornflour, cornstarch, maize starch, or corn starch (American English) is the starch derived from corn (maize) grain. The starch is obtained from the endosperm of the seed, kernel. Corn starch is a common food ingredient, often used to thick ...

and mineral oil. The indicator dye changes color with the onset of sweating. Digital photographs of the color change are recorded every 15 seconds over approximately 7 minutes. Spatial and temporal analysis of sweat droplets as well as direct and indirect sweat response are measured. Although QDIRT is less technically demanding than QSART or TST, it still requires trained staff and an environmentally controlled room; iontophoresis may cause skin irritation or burning; the skin areas studied using QDIRT are not pre-defined, thus limiting the interindividual comparability of the test; and little normative or performance data are available.

Sensitive Sweat Test (SST)

The SST was recently developed by Adam Loavenbruck and colleagues in 2017 for the evaluation of individual

s. It allows for the quantification of sweat from each individual sweat gland, as well as their location and distribution, thus providing both temporal and spatial resolution. The procedure is initiated by the iontophoresis of 0.5% pilocarpine solution over a 2.25 cm² skin area, which stimulates the underlying sweat glands directly through the activation of muscarinic M3 receptors. Immediately following iontophoresis, the skin is dried, and then covered with a 10% povidone-iodine solution. At the onset of sweating, the reaction of sweat with the povidone-iodine solution and corn starch results in the appearance of a black spot. A customized miniature camera can follow the secretions of up to 400 sweat glands at a time for up to 60 seconds, analyzing the enlargement rate and area of each spot. The test is then repeated for replicate analysis. The procedure is relatively quick and the camera is portable. However, further testing is needed to establish normative data and to confirm its utility in autonomic testing. As the test lacks an axon-reflex response, it has a limited ability to assess nerve fiber function.

Sympathetic Skin Response (SSR)

SSR refers to the change in skin resistance to electrical conduction associated with the sympathetic activation of sudomotor function in response to external or internal stimuli, such as electrical stimulation, deep breathing, and mental stress. It is mediated by a poorly understood somato-sympathetic reflex with spinal, bulbar, and suprabulbar components. The SSR is frequently utilized in psychophysiological studies and is a well-known component of the polygraph test. The test is performed using standard

electromyography Electromyography (EMG) is a technique for evaluating and recording the electrical activity produced by skeletal muscles. EMG is performed using an instrument called an electromyograph to produce a record called an electromyogram. An electromyo ...

(EMG) equipment in a lightly dimmed, humidity- and temperature-controlled room. A surface

is positioned on the patient’s palm or sole, along with a reference electrode on the dorsal side of the same body area. A change in skin potential is then induced either through electrical stimulation or deep breathing. The recorded SSR is then plotted on a graph and analyzed for presence or absence, latency, and amplitude. The SSR is thought to be mainly influenced by the

content of sweat secreted from eccrine glands. In addition, there is significant intra-individual and inter-individual variability, and SSR declines with age and is commonly absent in individuals over the age of 50. SSR is only considered a surrogate marker of sudomotor function and its results should be interpreted in the context of other sudomotor testing.

Spoon Test

The spoon test, developed in 1964 by Dr. Ernest Bors, relies on assessment of the smooth movement of the convex side of a spoon along the surface of the patient’s skin. In patients with sudomotor dysfunction, the spoon will slide in a smooth and uninterrupted fashion. Conversely, the spoon’s movement in normal controls will be frequently interrupted by the presence of sweat on the skin. The spoon test is inexpensive, easy to perform, but subjective and not quantitative.

Sweat Gland Nerve Fiber Density (SGNFD)

SGNFD can be quantified in skin biopsies taken from the distal leg, distal thigh, and proximal thigh prepared for standard analysis of intraepidermal nerve fiber density (IENFD). Nerve fibers innervating sweat glands are stained with Protein Gene Product 9.5 and quantified using manual morphometry with light microscopy. SGNFD can potentially be used as a surrogate anatomical marker for sudomotor function. However, it is not a direct assessment of the sweat response, and normative data must be established.

Minor's Test

Physical Examination

Inspection of the patient’s skin, particularly on the lower extremities, in conjunction with a thorough medical history, can provide valuable information regarding the possible presence of sudomotor dysfunction. Evidence of altered skin hydration, such as

, excessive skin dander, rhagades, and ulcers, can be suggestive of sudomotor dysfunction. Presence of intense foot odor may be another presentation.