Sudomotor

Sudomotor function refers to the autonomic nervous system control of sweat gland activity in response to various environmental and individual factors. Sweat production is a vital thermoregulatory mechanism used by the body to prevent heat-related illness as the evaporation of sweat is the body's most effective method of heat reduction and the only cooling method available when the air temperature rises above skin temperature. In addition, sweat plays key roles in grip, microbial defense, and wound healing.

Human sweat glands 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 follicles. 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 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 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 and medulla to preganglionic sympathetic cholinergic neurons in the intermediolateral column of the spinal cord. The preganglionic neurons synapse with postganglionic cholinergic sudomotor (and to a lesser extent adrenergic) neurons in the paravertebral sympathetic ganglia. When the action potential reaches the axon terminal of the postganglionic neuron, acetylcholine 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 storages and an influx of extracellular calcium which ultimately results in the movement of chloride ion (Cl⁻), sodium ion (Na⁺), and water into the duct lumen.

Impaired sudomotor function can occur in any disorder that directly and/or indirectly affects the autonomic nervous system, including diabetes mellitus, amyloidosis, infections, neurodegenerative diseases, multiple system atrophy, 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, rhagades, ulcerations, and poor wound healing 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 for diagnosis 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.

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