A retrospective chart review of patients who underwent skin biopsy testing for phosphorylated alpha-synuclein (P-SYN) was recently published in Movement Disorders Clinical Practice, the journal of the International Parkinson and Movement Disorders Society® (MDS).

A team of neurologists and researchers at Yale reviewed the charts of 300 patients who were administered a skin punch biopsy to determine how skin biopsy testing for P-SYN is used in the real-world diagnosis and management of synucleinopathies. How test results correlate with clinical presentation, and which demographic groups are using the test, were additional study aims.

Patients over 40 who underwent skin biopsy testing for suspected alpha-synucleinopathy between 2020 and 2023 were included in the final analysis of 149 cases. An additional 117 patients who underwent skin biopsy testing for small fiber neuropathy (SFN) served as a control group. The alpha-synuclein group was 52% male and the average age at time of biopsy was 73 years. The majority identified as white (83%) and not Hispanic or Latino (88%). The SFN group was significantly younger (59 years) and more likely to be female (72%).

Of the 149 cases, 105 (70%) were positive for P-SYN and 82 (55%) were positive for abnormal intraepidermal nerve fiber density. The test was typically used because of suspected Parkinson’s or other synucleinopathy, however 41 (28%) were ordered because of suspected dementia with Lewy bodies and 6 (4%) were ordered for suspected multiple system atrophy. There was no correlation between any specific pre-biopsy symptom, including among those who met MDS criteria for motor symptoms. 41 (73%) of patients who had motor symptoms were positive for P-SYN, a number that wasn’t significantly different from those who did not meet motor criteria, suggesting that the presence of motor symptoms may not be a necessary criteria for testing.

Changes in diagnosis following biopsy, defined as “…a clear change in chart diagnostic codes or an explicit strengthening of the suspected clinical diagnosis…,” occurred in more than half (52%) of cases. Disease management was changed in 60% of cases and most commonly included individualized patient counseling for a specific condition or disease-specific adjustments of medication.

A minority of patients (13%) had documented DaTscan results at the time of chart review. Of the seven patients with abnormal DaTscan results, five were positive for P-SYN. In 11 patients with normal DaTscan results, seven were positive for P-SYN.

“Our analysis reveals that skin biopsies are actively being used in the diagnosis and management of suspected α-synucleinopathies, with results impacting both aspects of medical decision-making in over half of the cases included in this cohort,” state the authors. They note that the test was mostly used in white, non-Hispanic patients, and that insurance coverage for the test is improving but not widely available.

“It is important to acknowledge that our field has not yet come to a consensus on the optimal biomarker for use in diagnostic frameworks,” the authors conclude, adding that “…skin biopsy has the potential to be a powerful tool for the diagnosis and management of α-synucleinopathies.”

Read the study