CurrentKaiser PermanentePolicy N/A

Synucleinopathies Testing for Movement Disorders (Syn-One)

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Clinical review criteria for use of Syn-One skin biopsy testing to aid diagnosis of synucleinopathies for Kaiser Foundation Health Plan of Washington members; covers Medicare and non‑Medicare determinations, documentation, and authorization guidance for movement disorder neurologists.

Policy Summary

PayerKaiser Permanente

PolicySynucleinopathies Testing for Movement Disorders (Syn-One)

Policy CodePolicy N/A

Change TypeCriteria adoption (MTAC-approved) and coverage specification

Effective DateJan 10, 2025

Last ReviewMay 6, 2025

Next Review DateN/A

Key ActionProvide the last 6 months of clinical notes from the requesting provider and/or specialist to support medical necessity.

SourceLink

POLICY UPDATE CHANGES

MTAC approved adoption of criteria for Syn-One for diagnosis of synucleinopathies for Medicare and non‑Medicare members.

Non‑Medicare criteria specifying when Syn‑One skin biopsy testing is considered medically necessary or not medically necessary for specific indications (Parkinson's disease, MSA, Lewy body disease, REM sleep disorder, other indications).

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CurrentKaiser PermanentePolicy N/A

Synucleinopathies Testing for Movement Disorders (Syn-One)

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Know when Kaiser Permanente releases new policies or updates existing guidance.

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Policy Summary

PayerKaiser Permanente

PolicySynucleinopathies Testing for Movement Disorders (Syn-One)

Policy CodePolicy N/A

Change TypeCriteria adoption (MTAC-approved) and coverage specification

Effective DateJan 10, 2025

Last ReviewMay 6, 2025

Next Review DateN/A

Key ActionProvide the last 6 months of clinical notes from the requesting provider and/or specialist to support medical necessity.

SourceLink

POLICY UPDATE CHANGES

MTAC approved adoption of criteria for Syn-One for diagnosis of synucleinopathies for Medicare and non‑Medicare members.

Coverage Criteria for Syn-One (alpha-synuclein skin biopsy)

inv-01: Non‑Medicare member coverage determinations

Covered when ALL of the following are met:

Parkinson's disease - medically necessary: Considered medically necessary when empiric therapy has been tried and did not lead to clinical improvement or caused significant side effects.empiric therapy trial failed or intolerant

Must be ordered by a neurologist who subspecializes in movement disorders.

Multiple system atrophy (MSA) - medically necessary: Considered medically necessary in the absence of pre-existing genetic testing confirming the diagnosis.no pre-existing genetic confirmation

Must be ordered by a neurologist who subspecializes in movement disorders.

Dementia with Lewy bodies (Lewy Body Disease) - not medically necessary: Not medically necessary due to insufficient evidence to support clinical utility.N/A

REM sleep behavior disorder (RBD) - not medically necessary: Not medically necessary due to insufficient evidence to support clinical validity.N/A

Sensitivity and specificity for RBD not established.

All other indications - not medically necessary: All other indications are considered not medically necessary.N/A

inv-02: Medicare members

When there is no active NCD or LCD:

Medicare application note: Kaiser Permanente uses the same Clinical Review Criteria for Medicare members in the absence of an active NCD or LCD; see Non‑Medicare criteria for specifics.N/A

Refer to the Non‑Medicare member coverage determinations above for specific indications and requirements.

Beyond the two indications for which Syn‑One may be considered medically necessary in non‑Medicare members (Parkinson disease and multiple system atrophy), the policy explicitly treats other suspected synucleinopathies and related presentations as not medically necessary. Lewy body disease (dementia with Lewy bodies) and rapid eye movement (REM) sleep disorder are listed as not medically necessary because the evidence does not support clinical utility or validity for these indications. The policy further states that all other indications not specifically listed are also not medically necessary.

Syn‑One testing (phosphorylated alpha‑synuclein skin biopsy) is considered not medically necessary for Lewy Body Disease, REM sleep disorder, and for any other non‑specified indications. The rationale provided in the policy is that there is insufficient evidence to support clinical utility for Lewy Body Disease and insufficient evidence to support clinical validity for REM sleep disorder; therefore these uses do not meet medical necessity criteria and may be denied for non‑Medicare members.

Relevant Procedure and Pathology Codes

Relevant pathology and immunofluorescence CPT codes referencedCPT

88305	Level IV - Surgical pathology, gross and microscopic examination
88314	Special stain including interpretation and report; histochemical stain on frozen tissue block
88346	Immunofluorescence, per specimen; initial single antibody stain procedure
88350	Immunofluorescence, per specimen; each additional single antibody stain procedure
88356	Morphometric analysis; nerve

Provider Actions, Documentation & Authorization

Prior Authorization

Preauthorization check advised for biopsy/immunofluorescence codes

Verify authorization requirements for the listed pathology and immunofluorescence procedure codes before scheduling or billing. Use the Pre-authorization Code Check to confirm whether prior authorization is required for the biopsy and immunofluorescence CPT codes associated with Syn-One testing.

Relevant CPT codes to check: 88305, 88314, 88346, 88350, 88356

Step Therapy

Stepwise requirement: empiric therapy trial required for Parkinson's disease

For Parkinson's disease, order Syn-One only after a documented trial of empiric therapy has failed to produce clinical improvement or the patient experienced significant side effects; the test must be ordered by a neurologist who subspecializes in movement disorders.

Document that empiric therapy was tried and either ineffective or not tolerated prior to ordering Syn-One
Ensure ordering provider is a movement disorders neurologist

Definitions and Test Description

Syn-One Test — key details

Assay descriptionA skin biopsy assay that detects abnormal phosphorylated alpha-synuclein in cutaneous nerves using immunofluorescence; provides pathological evidence to aid diagnostic evaluation but does not differentiate between synucleinopathy subtypes.

Target biomarkerPhosphorylated alpha-synuclein in peripheral (cutaneous) nerve fibers.

Recommended sample collection guidanceCollect three skin biopsy samples as recommended; use results alongside clinical features for diagnosis.

Background on Synucleinopathies and Test Context

Synucleinopathies are a group of neurodegenerative disorders characterized by deposition of phosphorylated alpha‑synuclein in central and peripheral nervous system tissues. The policy frames Syn‑One as a skin biopsy assay that detects phosphorylated alpha‑synuclein in peripheral (cutaneous) nerves to provide pathological evidence that can assist diagnosis. While this peripheral testing can support diagnosis in clinical context, the policy notes limitations in evidence for some conditions and does not claim that the test differentiates among synucleinopathy subtypes.

Revision History

2025-05-06MTAC/MPC approval

MPC approved adoption of criteria for Syn‑One for diagnosis of synucleinopathies for Medicare and non‑Medicare members (MTAC review noted earlier).

2025-10-01Effective dateLatest

Policy effective date following 60-day notice for adoption of Syn‑One clinical criteria for Medicare and non‑Medicare members.