Peripheral Synucleinopathy in Patients Diagnosed with Drug-induced Parkinsonism with Normal Dopamine Transporter Imaging
Virgilio Gerald Evidente1, Roy Freeman2, Todd Levine3, Danica Evidente1, Julia Phillips1, Christopher Gibbons2
1Movement Disorders Center of Arizona, 2Beth Israel Deaconess Medical Center, 3Honor Health
Objective:
To describe results of skin biopsy for phosphorylated alpha synuclein (P-SYN biopsy) in patients with drug-induced parkinsonism (DIP).
Background:
DIP is the second most common cause of parkinsonism after Parkinson's disease (PD). DIP and PD can coexist in the elderly. Dopamine transporter (DAT) imaging is used to differentiate between DIP and PD, being normal in DIP and abnormal in PD. We describe results of cutaneous P-SYN biopsy in elderly patients diagnosed with DIP.
Design/Methods:
We retrospectively reviewed records from the Movement Disorders Center of Arizona from 2012-2023 for patients with DIP who underwent P-SYN skin biopsy because of concern for possible overlapping PD.
Results:
We identified 16 patients with DIP with P-SYN biopsy; 11/16 were females. Average age at time of biopsy was 68.5±9.2 yrs (range=57-81). Causative drugs included aripiprazole (6), olanzapine (2), amiodarone (2), valproate (1), ziprasidone (1), risperidone (1), or combination of drugs (4). DAT scans were performed in 14/16(88%): 10/14(71%) were normal and 4/14(29%) were abnormal. Of the 10 with normal DAT scans, 6/10(60%) were P-SYN(+). Of the 4 with abnormal DAT scans, 3/4(75%) were P-SYN(+). Of the 16 DIP patients, 8/16(50%) were P-SYN(+): 7/8(88%) had P-SYN only in the neck, 1/8(12%) had P-SYN only in the distal leg. 7/8 (88%) had reduced intraepidermal nerve fiber density (IENFD) in the distal thigh and distal leg, and 1/9(12%) had reduced IENFD in the distal leg only. RBD was present in 3/16(19%) of DIP patient. 3/4 DAT(+) patients were tried on levodopa: 2/3(67%) were levodopa-responsive. 7/10(70%) of DAT(-) patients were tried on levodopa: 5/7(71%) were levodopa-responsive. 5/8 P-SYN(+) patients were tried on levodopa: 3/5(60%) were levodopa-responsive.
Conclusions:
Skin biopsy for P-SYN may be more sensitive than DAT scan in identifying DIP patients who may be at risk for developing PD or some other synucleinopathy.