Invited review Evaluation of sudomotor function Phillip A. Low * Department of Neurology, Mayo Foundation, 811 Guggenheim, 200 First Street SW, Rochester, MN 55905, USA Accepted 29 January 2004 Available online 17 March 2004 1. Why evaluate sudomotor function? The eccrine sweat gland is innervated by postganglionic sudomotor fibers. It plays an important role in thermo- regulation. A diffuse loss of function can result in heat intolerance and excessive function, manifest as hyperhi- drosis can be distressing. However, the importance of measurements of the sweat response resides in its value as an index of the severity and distribution of autonomic failure, and hence as an aid in the diagnosis of dysautono- mia. For instance, the percent anhidrosis on the thermo- regulatory sweat test (TST) correlates with the severity and distribution of generalized autonomic failure in multiple system atrophy (MSA) and other extrapyramidal disorders (Sandroni et al., 1991), in the autonomic neuropathies (Fealey et al., 1989; Low and Fealey, 1999). It may be the most sensitive test in detecting distal small fiber neuropathy (Stewart et al., 1992). 2. Anatomy and physiology of sweating Thermoreceptors are present in the preoptic-anterior hypothalamus area, responding to a deviation in core temperature relative to the temperature set point. However, other thermoreceptors in skin, viscera, and spinal cord are also important. Afferent impulses from these peripheral receptors travel in the spinothalamic tract afferent pathways, but also ascend as multisynaptic fiber pathways diffusely in the lateral spinal cord, to the reticular formation of the brain stem, and finally to the hypothalamus and thalamus. In addition to thermoreceptors, changes in fluid volume and electrolyte concentrations also affect thermoregulation. Dehydration results in central hyperosmolarity, which inhibits the firing of ‘warm’ neurons in the preoptic-anterior hypothalamus area, and reduces heat-dissipating responses. It has also been demonstrated that hyper- and hypovolemia, without changes in osmolarity, cause a rise and fall in body temperature, respectively, and much of the changes are mediated by neuropeptides. Thermoreceptors in the pre- optic-anterior hypothalamus area detect core temperature and integrate thermal information. The posterior hypothala- mus has been ascribed the role of setting the set point, although recent evidence suggests a more limited role. The set point is like an internal thermostat, a temperature point that regulating mechanisms work to maintain. Efferent pathways as crossed and uncrossed fibers from the hypothalamus travel via the tegmentum of the pons and the lateral reticular substance of the medulla to the intermediolateral column. Recent studies indicate that some fiber connections are polysynaptic (Saper, 2002). The intermediolateral column neurons are cholinergic and synapse with paravertebral sympathetic ganglia neur- ons. Emanating postganglionic sympathetic neurons that supply eccrine sweat glands are cholinergic sudomotor axons. There are about 5000 preganglionic neurons per segment of thoracic cord in humans. There is a progressive loss of these neurons and axons with increasing age with an attrition rate of 5–7% per decade (Low and Dyck, 1977, 1978; Low et al., 1977). The neural innervation of sudomotor dermatomes is less precise than sensory dermatomes (Johnson and Spalding, 1974) since a single ganglion receives fibers from 5 to 6 preganglionic levels and skin receives innervation from multiple roots. Approximate sudomotor dermatomes are: T1–2, ipsilateral face; T2–6, upper limb; T5–12, trunk; T10–L3, lower limb. As a rule, concordance of sudomotor dermatomes is good, once postganglionic fibers enter nerve trunk but poor proximal to that. There are two types of sweat glands, eccrine and apocrine, but only eccrine glands are responsible for the sweat response (Sato and Dobson, 1970). Apocrine glands will not be considered further. The eccrine sweat glands are Clinical Neurophysiology 115 (2004) 1506–1513 www.elsevier.com/locate/clinph 1388-2457/$30.00 q 2004 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.clinph.2004.01.023 * Tel.: þ 1-507-284-3375; fax: þ1-507-284-3133. E-mail address: low@mayo.edu (P.A. Low).