Objective: To describe results of skin biopsy for phosphorylated alpha-synuclein (P-SYN) in patients with essential tremor (ET) with parkinsonism.

Background: Patients with longstanding ET may develop subtle parkinsonian signs, most commonly a rest tremor. Elderly ET patients may present with parkinsonism due to advanced age or orthopedic issues. ET patients have increased risk of developing Parkinson’s disease (PD) compared to the normal population. ET patients who develop parkinsonism or other motor/nonmotor symptoms are referred to as ET-Plus. The dopamine transporter (DaT) scan is often performed to differentiate between ET with parkinsonism (ET-P) and PD, as it is normal in ET and abnormal in PD. Skin biopsy for P-SYN is positive in PD, multiple system atrophy (MSA) or dementia with lewy bodies (DLB), and negative in ET. The frequency of peripheral synucleinopathy in ET-P is unknown.

Method: We did a retrospective review of all ET-P patients seen in one center from 2012-2023 who had undergone P-SYN skin biopsy. The main reason for skin biopsy was presence of parkinsonian sign(s). We reviewed demographic data, presence of RBD, extrapyramidal exam, autonomic symptoms, DaT scan, cardiac MIBG scan, and University of Pennsylvania Smell Identification Test (UPSIT).

Results: We identified 24 patients with ET-P who had skin biopsy for P-SYN. 16/24 (67%) were men. 17/24 (71%) had a rest tremor. 7/24 (29%) had RBD. 15/24 (62%) had 2 or more autonomic symptoms. Average age at time of biopsy was 69.75 years (range=30-88). Average duration of ET at time of biopsy was 14.54 years (range=3-38). 23/24 (96%) had undergone DaT scans, of which 20/23 (87%) were normal. Of the 20 with normal DaT scans, 17/20 (85%) were positive (+) for P-SYN. Of the 24 ET-P patients, 20/24 (83%) were P-SYN(+), of which 19/20 (95%) had normal DaT scans. 13/24 (54%) had cardiac MIBG scans, of which 8/13 (61%) were abnormal; all 13 had normal DaT scans. 6/8 (75%) with abnormal cardiac MIBG scans were P-SYN(+). 16/24 (67%) ET-P patients had the UPSIT, of which 11/16 (69%) were abnormal. With smokers excluded, only 6/16 (38%) had abnormal UPSIT.

Conclusion: The majority of ET-P patients have evidence of peripheral synucleinopathy despite normal DaT scans. Our preliminary retrospective data suggests skin biopsy for P-SYN may help identify ET-P patients who may be at risk for developing PD, MSA or DLB.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/peripheral-synucleinopathy-in-essential-tremor-plus-patients-with-parkinsonian-features-and-normal-dopamine-transporter-imaging/