The human skin is a highly specialized organ for receiving sensory information but also to preserve the body's homeostasis. 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. 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. 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. Sensory fibers can be assessed using quantitative sensory test. 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. 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.

While new autonomic sudomotor function testings have been developed and studied over the past decades, the most were well-studied and established techniques QSART and TST remain the gold standard of sudomotor assessment. Combining these techniques allows for sophisticated analysis of neurally mediated sudomotor impairment. However, newer techniques display potential to complement gold standard techniques to further improve their precision and diagnostic value.

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 analyze 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.

Takotsubo cardiomyopathy (TTC) is an acute and reversible cardiac wall motion abnormality of the left myocardium. Although many studies focused on etiology, diagnostic and treatment of TTC, precise clinical guidelines on TTC are not available. Research revealed emotional and physical triggering factors of TTC and emphasized the association of TTC with psychiatric and particularly acute neurological disorders. Similar clinical presentation of acute coronary syndrome (ACS) and TTC patients, makes an anamnestic screening for TTC risk factors necessary. In psychiatric anamnesis affective disorders and chronic anxiety disorders are presumably for TTC. Subarachnoid hemorrhages and status epilepticus are typical acute neurological associated with a higher risk for TTC. Moreover, magnetic resonance imaging (MRI) studies reveled brain alterations of the limbic system and reduced connectivity of central autonomic nervous system structures. Diagnosis of TTC is made by elevation of cardiac enzymes, electrocardiogram (ECG) and visualization of myocardial wall motion. Major differential diagnoses like acute coronary syndrome and myocarditis are hereby in synopsis with anamnesis with respect of possible emotional and physical triggering factors of TTC ruled out. In most cases the TTC typical wall motion abnormalities resolve in weeks and therapy is only necessary in hemodynamic instable patients and if rare complications, like cardiac wall ruptures occur. Recently, the two-parted International expert consensus document on Takotsubo syndrome was published, providing a detailed characterization of TTC and allows clinicians to understand this cardiac dysfunction with a multidisciplinary view.