RT Journal Article
SR Electronic
T1 Cutaneous α-Synuclein Signatures in Patients With Multiple System Atrophy and Parkinson Disease
JF Neurology
JO Neurology
FD Lippincott Williams & Wilkins
SP e1529
OP e1539
DO 10.1212/WNL.0000000000206772
VO 100
IS 15
A1 Christopher Gibbons
A1 Ningshan Wang
A1 Sharika Rajan
A1 Drew Kern
A1 Jose-Alberto Palma
A1 Horacio Kaufmann
A1 Roy Freeman
YR 2023
UL http://n.neurology.org/content/100/15/e1529.abstract
AB Background and Objectives Multiple system atrophy (MSA) is a progressive neurodegenerative disorder caused by the abnormal accumulation of α-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 other synucleinopathies, particularly PD. The purpose of the study was to develop a unique cutaneous pathologic signature of phosphorylated α-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 3 locations. The density of intraepidermal, sudomotor, and pilomotor nerve fibers was measured. The deposition of phosphorylated α-synuclein was quantified. Results were compared with clinical rating assessments and autonomic function test results.Results Patients with PD had reduced nerve fiber densities compared with patients with MSA (p < 0.05, all fiber types). All patients with MSA and 51/54 with PD had evidence of phosphorylated α-synuclein in at least one skin biopsy. No phosphorylated α-synuclein was detected in controls. Patients with MSA had greater phosphorylated α-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 2 disorders.Discussion α-synuclein is present in the peripheral autonomic nerves of patients with MSA and when combined with synuclein distribution accurately distinguishes MSA from PD.Classification of Evidence This study provides Class II evidence that measurement of phosphorylated α-synuclein in skin biopsies can differentiate patients with MSA from those with PD.AUC=area under the curve; BIDMC=Beth Israel Deaconess Medical Center; IENFD=intraepidermal nerve fiber density; MDS-UPDRS=Movement Disorders Society Unified Parkinson's Disease Rating Scale; MSA=multiple system atrophy; NYU=New York University; OHQ=Orthostatic Hypotension Questionnaire; P-SYN=phosphorylated α-synuclein; PD=Parkinson disease; RBD=REM sleep behavior disorder; ROC=receiver operating characteristic; UMSARS=Unified Multiple System Atrophy Rating Scale; UPSIT=University of Pennsylvania Smell Identification Test