Clinical Utility of Skin Biopsy for Cutaneous Phosphorylated Alpha-synuclein in Cognitive Manifestations of Lewy Body Disease
Michael Rigby1, Hugo Botha1, Leland Barnard1, Zachary Trottier1, Aaron Switzer3, Vijay Ramanan1, Bryan Neth1, Rodolfo Savica1, David Jones1, Toji Miyagawa1, Erik St. Louis2, David Knopman1, Ronald Petersen1, Jonathan Graff-Radford1, Bradley Boeve1, Stuart McCarter2
1Neurology, 2Neurology, Mayo Center for Sleep Medicine, Mayo Clinic, 3Neurology, University of Calgary
Objective:
To evaluate the frequency of positive skin biopsies for alpha-synuclein in patients with cognitive symptoms in an academic memory clinic.
Background:
The clinical presentation of dementia with Lewy bodies (DLB) is complex and diagnostically challenging. Immunohistochemically detected cutaneous phosphorylated alpha-synuclein was reported in 96% of DLB cases in a prior study in those meeting strict consensus criteria for DLB. The utility of this test in clinical practice and those with prodromal DLB (mild cognitive impairment, MCI-LB) is unknown.
Design/Methods:
Forty-nine patients with cognitive symptoms underwent commercially available skin biopsy at three sites (posterior cervical, distal thigh, distal leg) for cutaneous phosphorylated alpha-synuclein as part of their clinical evaluation. Retrospective chart review determined if individuals met published criteria for probable DLB or MCI-LB, blinded to skin biopsy result. Descriptive statistics are reported.
Results:
Average age at skin biopsy was 70.0±1.4 years, with 80% male. Thirty-two patients (65%) had a positive skin biopsy (at least one of three sites). Of the 39 patients who met blinded clinical criteria for DLB/MCI-LB, 27 (69%) had a positive skin biopsy with similar frequency between subgroups (DLB 65%; MCI-LB 78%). Of the 31 patients who were determined to have DLB/MCI-LB by the treating physician, 27 (87%) had a positive skin biopsy, with the 3 of 4 negative tests having FDG-PET hypometabolism supportive of DLB. In 80% of cases, the skin biopsy result supported the initial suspected diagnosis. Of 18 patients thought not to have synucleinopathy, 5 (28%) had a positive skin biopsy. Alternative diagnoses in biopsy positive cases were anti-DPPX autoimmunity, anti-GFAP autoimmunity, hydrocephalus/epilepsy, OSA/anxiety, and refractory depression.
Conclusions:
Positive skin biopsy for phosphorylated alpha-synuclein is common in prodromal and overt DLB, however, at a lower frequency than previously reported. Given the heterogenous presentations of DLB, more studies are needed to optimize clinical utility.
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