Sudomotor dysfunction is one of the earliest detectable neurophysiologic abnormalities in distal small fiber neuropathy. Traditional neurophysiologic measurements of sudomotor function include thermoregulatory sweat testing (TST), quantitative sudomotor axon reflex testing (QSART), silicone impressions, the sympathetic skin response (SSR), and the recent addition of quantitative direct and indirect axon reflex testing (QDIRT). These testing techniques, when used in combination, can detect and localized pre-and postganglionic lesions, can provide early diagnosis of sudomotor dysfunction and can monitor disease progression or disease recovery. In this article, we review the common tests available for assessment of sudomotor function, detail the testing methodology, review the limitations and provide examples of test results.

Objective: To evaluate a novel method to quantify the density of nerve fibers innervating sweat glands in healthy control and diabetic subjects, to compare the results to an unbiased stereologic technique, and to identify the relationship to standardized physical examination and patientreported symptom scores.Methods: Thirty diabetic and 64 healthy subjects had skin biopsies performed at the distal leg and distal and proximal thigh. Nerve fibers innervating sweat glands, stained with PGP 9.5, were imaged by light microscopy. Sweat gland nerve fiber density (SGNFD) was quantified by manual morphometry. As a gold standard, three additional subjects had biopsies analyzed by confocal microscopy using unbiased stereologic quantification. Severity of neuropathy was measured by standardized instruments including the Neuropathy Impairment Score in the Lower Limb (NIS-LL) while symptoms were measured by the Michigan Neuropathy Screening Instrument.Results: Manual morphometry increased with unbiased stereology (r ϭ 0.93, p Ͻ 0.01). Diabetic subjects had reduced SGNFD compared to controls at the distal leg (p Ͻ 0.001), distal thigh (p Ͻ 0.01), and proximal thigh (p Ͻ 0.05). The SGNFD at the distal leg of diabetic subjects decreased as the NIS-LL worsened (r ϭ Ϫ0.89, p Ͻ 0.001) and was concordant with symptoms of reduced sweat production (p Ͻ 0.01). Conclusions:We describe a novel method to quantify the density of nerve fibers innervating sweat glands. The technique differentiates groups of patients with mild diabetic neuropathy from healthy control subjects and correlates with both physical examination scores and symptoms relevant to sudomotor dysfunction. This method provides a reliable structural measure of sweat gland innervation that complements the investigation of small fiber neuropathies. Assessment of small myelinated and unmyelinated nerve fibers is a central component of the evaluation of peripheral nerve disease. 1,2 Most polyneuropathies prominently target small nerve fibers; the subsequent small fiber dysfunction, impaired sensory perception, and sudomotor deficits lead to a predisposition to limb ulceration, infection, and amputation.3 Small sensory fiber function is evaluated with quantitative sensory testing while skin biopsy quantification of intraepidermal nerve fiber density (IENFD) provides a structural measure of small fiber cutaneous innervation. 4 Functional measures of peripheral postganglionic autonomic sudomotor nerves include the quantitative sudomotor axon reflex test (QSART) and silicone impression

Randomized controlled trials (RCTs) are the hallmark of evidence-based medicine and form the basis for translating research data into clinical practice. This review summarizes commonly applied designs and quality indicators of RCTs to provide guidance in interpreting and critically evaluating clinical research data. It further reflects on the principle of equipoise and its practical applicability to clinical science with an emphasis on critical care and neurological research. We performed a review of educational material, review articles, methodological studies, and published clinical trials using the databases MEDLINE, PubMed, and ClinicalTrials.gov. The most relevant recommendations regarding design, conduction, and reporting of RCTs may include the following: 1) clinically relevant end points should be defined a priori, and an unbiased analysis and report of the study results should be warranted, 2) both significant and nonsignificant results should be objectively reported and published, 3) structured study design and performance as indicated in the Consolidated Standards of Reporting Trials statement should be employed as well as registration in a public trial database, 4) potential conflicts of interest and funding sources should be disclaimed in study report or publication, and 5) in the comparison of experimental treatment with standard care, preplanned interim analyses during an ongoing RCT can aid in maintaining clinical equipoise by assessing benefit, harm, or futility, thus allowing decision on continuation or termination of the trial.

Introduction-Peripheral sudomotor dysfunction is present in many peripheral neuropathies, but structural assessments of sudomotor fibers rarely occur.