![]() ![]() ![]() These nerve fibers derive from perikarya located in the dorsal root and sympathetic ganglia. The cutaneous innervation consists of both autonomic (predominantly sympathetic but in face also parasympathetic) and sensory nerve fibers ( 10, 11). An easily accessible model of peripheral small nerve fibers is the study of the cutaneous nervous system, which is also impaired by small fiber neuropathies and due to its involvement in some neurodegenerative disorders has been referred to a “window into brain pathology” ( 9). To optimize treatment and identify new therapeutic targets, it is essential to acknowledge the architecture and physiology of the peripheral small nerve fibers. When causative therapy is not available personalized symptomatic treatment regimens can substantially improve quality of life. Modern treatments are chiefly directed to the pathophysiological mechanisms causing selective damage to small nerve fibers. Assessment of functional integrity of these nerve fibers can be performed using Laser doppler flowmetry (LDF), two-dimensional Laser doppler imaging (LDI) as well as axon-reflex based tests of sudomotor and pilomotor function such as the quantitative sudomotor axon reflex test (QSART) and the quantitative pilomotor axon reflex test (QPART) ( 4– 8). #Somatic nervous system effector organs skinThe most commonly used technique in terms of quantitative and qualitative analyses is the skin biopsy, including different immunohistochemical staining methods which are either not fiber specific or allow specific analysis of cholinergic or adrenergic nerve fibers. Only a few diagnostic techniques are available to assess peripheral small fiber neuropathy. Autonomic small fiber neuropathy has been associated with increased morbidity and mortality in patients with diabetes or cardiovascular disease ( 1– 3). This condition affects approximately 53 per 100.000 people and the most common etiologies are diabetes, neurodegenerative diseases, and complex regional pain syndrome due to trauma and paraneoplastic syndromes ( 1). Small fiber neuropathy is a condition which leads to impaired functional integrity of unmyelinated autonomic or somatic small nerve fibers. Here, we reviewed the current literature on the anatomy and functional pathways of the cutaneous autonomic nervous system as well as diagnostic techniques to assess its functional and structural integrity. Complementing these functional assessments, immunohistochemical staining of superficial skin biopsies allow analysis of structural integrity of cutaneous nerve fibers, a technique which has gained attention due to its capacity of detecting pathogenic depositions of alpha-synuclein in patients with Parkinson's disease. Sensory fibers can be assessed using quantitative sensory test. Functional integrity of autonomic skin nerve fibers can be assessed by quantitative analysis of cutaneous responses to local pharmacological induction of axon reflex responses which result in dilation of cutaneous vessels, sweating, or piloerection depending on the agent used to stimulate this neurogenic response. Knowledge on structure and function of these nerve fibers is relevant as they are selectively targeted by various autonomic neuropathies such as diabetic neuropathy or Parkinson's disease. These functions are mediated by cutaneous small nerve fibers which display a complex anatomical architecture and are commonly classified into cutaneous A-beta, A-delta and C-fibers based on their diameter, myelinization, and velocity of conduction of action potentials. The human skin is a highly specialized organ for receiving sensory information but also to preserve the body's homeostasis. 3Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.2Department of Neurosurgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.1Department of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.Buchmann 1, Mido Max Hijazi 2, Ben Min-Woo Illigens 3 and Timo Siepmann 1 * ![]()
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