Skin Biopsy May Help to Distinguish Multiple System Atrophy–Parkinsonism from Parkinson's Disease With Orthostatic Hypotension

Vincenzo Donadio, Alex Incensi, Giovanni Rizzo, Rosa De Micco, Alessandro Tessitore, Francesca Del Sorbo, Grazia Devigili, Salvatore Bonvegna, Rossella Infante, Martina Magnani, Corrado Zenesini, Luca Vignatelli, Roberto Cilia, Roberto Eleopra, Gioacchino Tedeschi, Rocco Liguori

Research output: Contribution to journalArticlepeer-review


Background: The differential diagnosis between multiple system atrophy parkinsonism type (MSA-P) and Parkinson's disease with orthostatic hypotension (PD+OH) is difficult because the 2 diseases have a similar clinical picture. The aim of this study is to distinguish MSA-P from PD+OH by immunostaining for abnormal phosphorylated α-synuclein at serine 129 (p-syn) in cutaneous nerves. Method: We recruited 50 patients with parkinsonism and chronic orthostatic hypotension: 25 patients fulfilled the diagnostic criteria for MSA-P and 25 patients for PD+OH. The patients underwent a skin biopsy from the cervical area, thigh, and leg to analyze somatic and autonomic skin innervation and p-syn in skin nerves. Results: Intraneural p-syn positivity was found in 72% of patients with MSA-P, mainly in distal skin sites. More important, p-syn deposits in MSA-P differed from PD+OH because they were mainly found in somatic fibers of subepidermal plexi, whereas scant autonomic fiber involvement was found in only 3 patients. All patients with PD+OH displayed widely distributed p-syn deposits in the autonomic skin fibers of proximal and distal skin sites, whereas somatic fibers were affected only slightly in 4 patients with PD+OH. Skin innervation mirrored p-syn deposits because somatic innervation was mainly reduced in MSA-P. Sympathetic innervation was damaged in PD+OH but fairly preserved in MSA-P. Conclusions: The p-syn in cutaneous nerves allows the differentiation of MSA-P from PD+OH; MSA-P mainly shows somatic fiber involvement with relatively preserved autonomic innervation; and by contrast, PD+OH displays prevalent abnormal p-syn deposits and denervation in autonomic postganglionic nerves.

Original languageEnglish
Pages (from-to)1649-1657
Number of pages9
JournalMovement Disorders
Issue number9
Publication statusPublished - Sep 1 2020


  • misfolded alpha-synuclein
  • multiple system atrophy
  • orthostatic hypotension
  • parkinsonism
  • skin biopsy

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Fingerprint Dive into the research topics of 'Skin Biopsy May Help to Distinguish Multiple System Atrophy–Parkinsonism from Parkinson's Disease With Orthostatic Hypotension'. Together they form a unique fingerprint.

Cite this