Objective Recent studies suggest that sensory phenotyping may provide critical information for the diagnosis and management of patients with chronic neuropathic pain (NP). However, many formal quantitative sensory testing (QST) paradigms require expensive equipment, a dedicated location, and substantial time commitments on the part of patient and examiner, highlighting the need for a convenient and portable “bedside” QST battery. We developed and tested a bedside QST battery in a sample of patients with chronic NP. Methods Participants (N = 51) attended two in-person visits over approximately two weeks, during which they underwent QST using both laboratory-based equipment and simple, easily accessible bedside tools. Participants also completed questionnaires about their daily pain and NP symptoms. Results Test–retest reliability estimates were highly statistically significant and did not differ between bedside (mean r = 0.60) and laboratory-based (mean r = 0.72) QST. Bedside QST variables and corresponding laboratory-based QST variables were highly correlated, suggesting adequate criterion validity for the bedside tests. Conclusions Results from the present study may have important implications for the sensory phenotyping and subsequent management of patients with chronic NP. Implementation of a protocol that uses inexpensive, portable, and convenient tools may allow for the application of QST in variety of clinical settings and advance NP research.

Introduction/Aims Small fiber neuropathies (SFN) have been associated with two autoantibodies, trisulfated heparin disaccharide (TS‐HDS) and fibroblast growth factor receptor 3 (FGFR‐3), and intravenous immune globulin (IVIG) has been suggested as a potential therapy. The study objective is to determine the efficacy of IVIG on nerve density, pain and neurologic examinations in patients with SFN associated with TS‐HDS and FGFR‐3 autoantibodies. Methods This was a double‐blind placebo‐controlled pilot study. Subjects with SFN confirmed by history, examination, and skin biopsy with elevated autoantibodies to TS‐HDS and/or FGFR‐3 received IVIG (or blinded placebo) 2 grams/kg followed by 1 gram/kg every 3 wk for a total of 6 treatments. All subjects had Utah Early Neuropathy Scores (UENS), questionnaires and skin biopsies with quantitation of intra‐epidermal nerve fiber density (IENFD) taken from adjacent sites at the distal leg at baseline and 6 mo later. The primary outcome was the change in IENFD over 6 mo. Results Twenty subjects were enrolled; 17 completed treatment (8 IVIG, 9 placebo). Three did not have final data due to coronavirus disease 2019 (COVID‐19). Skin biopsy IENFD improved by 0.5 ± 0.8 fibers/mm in the placebo group and improved by 0.6 ± 0.6 fibers/mm in the IVIG‐treated group (p = NS).Over 24 wk the change in pain scores (11 point pain scale) was −1.9 ± 2.6 in the placebo group, and − 1.7 ± 0.9 in the IVIG group (p = NS), the UENS improved by 3.0 ± 5.8 in the placebo group and improved by 1.8 ± 3.9 in the IVIG group (p = NS). Discussion This pilot study did not detect a benefit of treatment with IVIG in patients with SFN and autoantibodies to TS‐HDS and FGFR‐3.

Background:Multiple system atrophy (MSA) is a progressive neurodegenerative disorder caused by the abnormal accumulation of alpha-synuclein in the nervous system. Clinical features include autonomic and motor dysfunction, which overlap with those of Parkinson disease (PD), particularly at early disease stages. There is an unmet need for accurate diagnostic and prognostic biomarkers for MSA, and, specifically, a critical need to distinguish MSA from the other synucleinopathies, particularly PD. The purpose of the study was to develop a unique cutaneous pathological signature of phosphorylated alpha-synuclein that could distinguish patients with MSA from patients with PD and healthy controls.Methods:We studied 31 patients with MSA and 54 patients with PD diagnosed according to current clinical consensus criteria. We also included 24 matched controls. All participants underwent neurologic examinations, autonomic testing and skin biopsies at three locations. The density of intra-epidermal, sudomotor and pilomotor nerve fibers was measured. The deposition of phosphorylated alpha-synuclein was quantified. Results were compared to clinical rating assessments and autonomic function test results.Results:Patients with PD had reduced nerve fiber densities compared to patients with MSA (P<0.05, all fiber types). All patients with MSA and 51/54 with PD had evidence of phosphorylated alpha-synuclein in at least one skin biopsy. No phosphorylated alpha-synuclein was detected in controls. Patients with MSA had greater phosphorylated alpha-synuclein deposition (P<0.0001) and more widespread peripheral distribution (P<0.0001) than patients with PD. These results provided >90% sensitivity and specificity in distinguishing between the two disorders.Discussion:Alpha-synuclein is present in peripheral autonomic nerves of MSA patients, and when combined with synuclein distribution, accurately distinguishes MSA from PD.Classification of Evidence:This study provides Class II evidence that measurement of phosphorylated alpha-synuclein in skin biopsies can differentiate patients with MSA from those with PD.