117 calculated using automatic software (ACCMetrics).30 Images from both eyes were selected by visual inspection of their quality. Age- and sex-stratified reference values from healthy volunteers were used to define impaired corneal parameters. Sudoscan Electrochemical skin conductance (ESC) was measured on both hands and feet with the Sudoscan® (Impeto Medical, Paris, France) to assess autonomic sudomotor function. Two stainless steel electrodes generated a low-voltage electric current. ESC (µS) for palms and soles was automatically calculated by the Sudoscan computer. Lower limits of 57 µS for the hands and 71 µS for the feet were used.31 Water immersion skin wrinkling Water immersion skin wrinkling was used to assess another aspect of autonomic function. The right hand was placed in water at 40 C for 30 minutes. Photos were taken afterwards to store in a database. The degree of wrinkling on the right hand was compared with the left hand as a reference. Wrinkling was graded between no wrinkling (grade 0) and wrinkling with complete deformation of the fingertip (grade 4).32 Statistics SPSS (v26, IBM, Armonk, NY, USA), Rstudio (v4.3.1, Rstudio, Boston, MA, USA) and Graphpad Prism (v8.4.3, GraphPad Software, San Diego, CA, USA) were used for statistical analysis. Chi-square was used to determine statistical significance between the prevalence of intermittent and continuous pain with a length-dependent and non-length-dependent presentation. Spearman’s rank correlation coefficient was used to assess the association between phenotypes and diagnostic parameters. Finally, the Mann-Whitney U test was used to determine statistical significance between TTT NOAs in patients with and without continuous length-dependent pain. Results Patient selection A total of 79 patients with sarcoidosis participated in this study, of whom 48 could be diagnosed with probable SFN (Figure 2). Demographic data are shown in Table 2. Table 2 Patient characteristics in healthy controls and patients with sarcoidosis (mean±sd) Group Sarcoidosis with SFN n 48 Age (yrs) 52±9 Sex Males (n (%)) 21 (44) Height 176±11 BMI 28±6 Disease duration sarcoidosis (yrs) 9±7 BMI = body mass index; SFN = small fiber neuropathy; yrs = years Symptoms mentioned during neurological consultation An overview of SFN-related symptoms reported by the participants is shown in Table 3. Pain, burning sensations and paresthesia were most frequently prevalent and observed in 50%, 44% and 42% respectively. 7 123 7
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