Skin Biopsy Distinguishes Between Parkinson's and 'Look-Alike' Disorder with High Degree of Accuracy, Study Shows

Improved Diagnostics Represent a Step Toward Precision Neurological Therapy

BOSTON – Multiple system atrophy (MSA) is a rare, rapidly progressive neurodegenerative disorder that affects up to 50,000 adults in the United States. MSA affects both motor control as well as the autonomic nervous system, which controls involuntary bodily functions such as blood pressure, bowel and bladder control. Patients with MSA may also experience muscle rigidity, tremor, loss of coordination and difficulties with speech or gait – symptoms that might be mistaken for Parkinson’s disease, a far more common neurodegenerative disorder. The overlapping features between MSA and Parkinson's disease create an unmet need for an accurate diagnostic biomarker.

Now, physician-scientists at Beth Israel Deaconess Medical Center (BIDMC) have demonstrated that a skin test that measures the deposition and distribution of the protein linked with neurodegeneration in the two diseases can differentiate patients with MSA from those with Parkinson’s disease with a high degree of accuracy. The team’s findings, published in the journal Neurology, open the door to improved diagnostics and have important implications for clinical care, research and life planning for patients with MSA.

“Parkinson's disease and MSA are look-alike disorders that are frequently confused, however, MSA patients do not respond to the typical Parkinson's disease treatments and MSA is rapidly progressive while Parkinson's disease patients may live for decades,” said senior author Roy Freeman, MD, director of the Center for Autonomic and Peripheral Nerve Disorders at BIDMC and professor of neurology at Harvard Medical School.

“Given the differences in the underlying pathology, natural history and prognosis of the two disorders, it is essential to accurately diagnose patients with MSA,” added co-first author Christopher Gibbons, MD, a neurologist at BIDMC and an associate professor of neurology at Harvard Medical School.

The skin test measures the presence and distribution of phosphorylated α-synuclein (P-SYN) – an abnormal protein implicated in neurodegenerative diseases – in the nerve fibers in the skin. To test its ability to distinguish between MSA and Parkinson’s disease, Gibbons and colleagues studied 31 patients diagnosed with MSA and 54 patients diagnosed with Parkinson’s disease as well as 24 healthy volunteers as age-matched control subjects. All participants underwent neurologic examinations, autonomic function testing and skin biopsies taken from the lower thigh, upper thigh and neck.

The scientists found that P-SYN was present in the nerve fibers found in the skin in all patients with MSA and nearly all patients with Parkinson’s disease (94 percent), but none of the control subjects. Analysis revealed significantly higher levels of P-SYN deposits in the nerves of patients with MSA compared to those of Parkinson's disease. Moreover, Gibbons and colleagues found that P-SYN was more evenly distributed across the bodies of patients with MSA than in patients with Parkinsons’ disease. That is, in patients with MSA, nerve fibers from the neck area were positive for P-SYN in 84 percent of cases, the upper thigh in 87 percent of cases, and distal thigh in 77 percent of cases. In patients with Parkinson’s, however, nerve fibers from the neck area were positive for P-SYN in 93 percent of cases, with positive cases in the proximal thigh and distal thigh dropping down sharply to 33 and 17 percent respectively.

Finally, the scientists were also able to show patients with PD have a loss of sensory and autonomic nerve fibers that is not present in patients with MSA.

“This study’s results show that MSA patients can be differentiated from those with Parkinson’s disease and healthy controls with high sensitivity and specificity using neuropathological signatures in skin samples,” said Freeman. “Collectively these data suggest that skin biopsy may be an accurate method to pathologically confirm a diagnosis and distinguish between MSA and Parkinson’s.”

Co-authors included co-first author Ningshan Wang, PhD, of BIDMC; Sharika Rajan, MD, of the National Institutes of Health; Drew Kern, MD, of University of Colorado; and Jose-Alberto Palma and Horacio Kaufman, MD, of NYU Grossman School of Medicine.

This work was funded by the National Institutes of Health (NIH U54 NS0657360); the Langer Family Foundation; and the MSA Coalition and University of Colorado Skin Disease Research Center. Gibbons is a scientific advisor and has stock options in CND Life Sciences. Freeman is a scientific advisor and has stock options in and previously served on the board of directors of CND Life Sciences. Please view the article published in Neurology for full disclosures.