ModifiedEmblemHealthPolicy AHS-G2123

Biomarker Testing for Multiple Sclerosis and Related Neurologic Diseases - Lab Benefit Program (LBM)

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Defines coverage criteria for laboratory biomarker tests (CSF and serum) used in diagnosis and differentiation of multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and MOG-IgG-associated disease for EmblemHealth's Lab Benefit Program (LBM); applies to claims and providers submitting tests under the payer's reimbursement rules.

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ModifiedEmblemHealthPolicy AHS-G2123

Biomarker Testing for Multiple Sclerosis and Related Neurologic Diseases - Lab Benefit Program (LBM)

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Policy Summary

PayerEmblemHealth

PolicyBiomarker Testing for Multiple Sclerosis and Related Neurologic Diseases - Lab Benefit Program (LBM)

Policy CodePolicy AHS-G2123

Change TypeNew policy effective 02/13/2026 (reformatted and renumbered)

Effective DateFeb 13, 2026

Last ReviewOct 1, 2025

Next Review DateFeb 13, 2026

Key ActionFollow Lab Benefit Program reimbursement guidance and applicable billing rules when ordering and submitting claims for biomarker tests; claims may be denied or recouped if coding/billing guidelines are not followed.

SourceLink

POLICY UPDATE CHANGES

New Policy effective 2/13/2026

Reformatted and reorganized policy, transferred content to new template with new Reimbursement Policy Number

meets criteriaOCB testing

meets criteriaAQP4/MOG by CBA/FACS

not coveredOther serum biomarkers

ELISA/Western blot/IHCExcluded methods

40+Evidence refs

Coverage Criteria for Biomarker Testing

inv-01: Coverage criteria for biomarker testing

Coverage determinations for biomarker testing under the Lab Benefit Program (LBM).

ALL of the following

ANY of the following
- Atypical clinical, laboratory, or imaging features (CSF OCB testing meets coverage).
- Atypical clinically isolated syndrome (including primary progressive or relapsing–remitting presentations).
- Members belonging to populations in which MS is less common (e.g., children, older individuals).
- Insufficient clinical or imaging evidence to establish a diagnosis of MS.

ALL of the following

All other serum biomarker tests for multiple sclerosis (in situations not meeting the specific coverage criteria above) — do not meet coverage due to insufficient published evidence of clinical benefit.
ELISA, Western blot, immunohistochemistry, or any other serum assays to test for NMOSD or MOG-EM — do NOT meet coverage criteria.
All other CSF biomarker tests for diagnosis of MS, NMOSD, or MOG-EM (including CSF AQP4-IgG or CSF MOG-IgG) — do NOT meet coverage criteria.

ALL of the following

Serum AQP4-IgG and MOG-IgG coverage is limited to cell-based indirect fluorescence assays or FACS methods as specified; other assay methods are excluded.

inv-02: Diagnostic and testing criteria / evidence — NMOSD diagnostic criteria and core clinical characteristics

NMOSD diagnostic criteria and core clinical characteristics (as cited from the International Panel):

ALL of the following

At least 1 core clinical characteristic is present.
Positive test for AQP4-IgG using the best available detection method (cell-based assay strongly recommended).
Exclusion of alternative diagnoses.

ALL of the following

At least 2 core clinical characteristics from one or more attacks, with at least one being optic neuritis, acute myelitis with LETM, or area postrema syndrome.

inv-03: Coverage overview (partial) — reimbursement policy scope, coding references, and regulatory context

This reimbursement policy provides coding references and regulatory context for biomarker testing used in diagnosis and management of MS and related disorders. Specific coverage criteria, indications, and limitations are defined elsewhere in the full policy.

ALL of the following

Laboratory-developed tests (LDTs) are regulated by CMS under CLIA as high-complexity tests; LDTs are not FDA-cleared/approved but FDA approval is not required for clinical use.
The KRONUS Aquaporin-4 Autoantibody (AQP4Ab) ELISA Assay received FDA approval in 2016 for semiquantitative determination of AQP4 autoantibodies in serum; it is described as an aid in diagnosis and should be used with other clinical, laboratory, and radiological findings (not as a standalone test).

ALL of the following

Procedure code references for biomarker testing (examples): 83520 (immunoassay), 83884 (NfL), 83916 (oligoclonal bands), 86051–86053 (AQP4 assays: ELISA, CBA, FACS), 86362–86363 (MOG-IgG CBA/FACS), and 88341–88342 (IHC procedures). Procedure codes listed are for reference and may not be all-inclusive.

Coding and Procedure Codes

Coding guidancemixed

No codes listed

Test types and regulatory statusmixed

LDT	Laboratory-developed tests regulated under CLIA as high-complexity tests (not FDA-cleared/approved)
AQP4 ELISA (KRONUS)	FDA-approved semiquantitative assay for AQP4 autoantibodies (approved 2016) — to be used with other clinical data

Referenced laboratory procedure codesCPT

83520	Immunoassay for analyte other than infectious agent antibody or infectious agent antigen; quantitative, not otherwise specified.
83884	Neurofilament light chain (NfL).
83916	Oligoclonal immune (oligoclonal bands).
84182	Protein; Western Blot, with interpretation and report, blood or other body fluid, immunological probe for band identification, each.
86051	Aquaporin-4 (neuromyelitis optica [NMO]) antibody; enzyme-linked immunosorbent immunoassay (ELISA).
86052	Aquaporin-4 (neuromyelitis optica [NMO]) antibody; cell-based immunofluorescence assay (CBA), each.
86053	Aquaporin-4 (neuromyelitis optica [NMO]) antibody; flow cytometry (ie, fluorescence- activated cell sorting [FACS]), each.
86362	Myelin oligodendrocyte glycoprotein (MOG-IgG1) antibody; cell-based immunofluorescence assay (CBA), each.
86363	Myelin oligodendrocyte glycoprotein (MOG-IgG1) antibody; flow cytometry (ie, fluorescence-activated cell sorting [FACS]), each.
88341	Immunohistochemistry or immunocytochemistry, per specimen; each additional single antibody stain procedure (List separately in addition to code for primary procedure).

1–10 of 11

1/2

inv-07: IgG index threshold — >0.7 (PPV >99% for OCBs)

IgG index threshold>0.7

Positive predictive value>99% for OCBs (Simonsen et al. retrospective study)

Negative predictive value26.5% for normal IgG predicting negative OCBs

Provider Billing, Claims, and Reimbursement Actions

Billing Rule

Reimbursement Policy (LBM)

Biomarker Testing for Multiple Sclerosis and Related Neurologic Diseases is subject to the Lab Benefit Program (LBM) reimbursement rules. Follow current LBM reimbursement guidance, billing and claims payment policies, and any applicable provider manual or newsletters for coverage determination and payment. Failure to follow applicable coding/billing guidelines or current reimbursement policies may result in claim denial and/or recoupment.

Follow the Lab Benefit Program (LBM) reimbursement guidance when ordering and billing tests.
We follow coding edits based on CPT guidelines, CMS (including NCCI and MUE), and industry-standard claims editing software.
Other factors (member benefit documents, contracts, legislative mandates, and other policies) may affect reimbursement and supersede this policy.
Upon request, EmblemHealth will provide explanations of how specific coding issues are handled.

Billing Rule

Key Terms and Test Definitions

inv-11: Key laboratory and disease terms (OCB, CSF, AQP4-IgG, MOG-IgG, etc.)

OCBOligoclonal immunoglobulin G band (CSF)

CSFCerebrospinal fluid

AQP4-IgG / AQP4AbAquaporin-4 immunoglobulin G / Aquaporin-4 autoantibody

MOG-IgG / MOGMyelin oligodendrocyte glycoprotein immunoglobulin G

CBACell-Based immunofluorescence assay (cell-based assay)

FACSFluorescence-activated cell sorting (flow cytometry-based assay)

ELISAEnzyme-linked immunosorbent assay

Policy Revision History

2026-02-13policy_activationLatest

New policy became effective and assigned reimbursement policy number AHS-G2123.

2025-10-01administrative_revision

Prior revision recorded for EmblemHealth (entry dated 10/2025).

2026-02-13administrative_reformat

Policy Summary

PayerEmblemHealth

PolicyBiomarker Testing for Multiple Sclerosis and Related Neurologic Diseases - Lab Benefit Program (LBM)

Policy CodePolicy AHS-G2123

Change TypeNew policy effective 02/13/2026 (reformatted and renumbered)

Effective DateFeb 13, 2026

Last ReviewOct 1, 2025

Next Review DateFeb 13, 2026

SourceLink

On This Page

Dissemination in space (two or more different core clinical characteristics).

Fulfillment of additional MRI requirements, as applicable.

Negative or unavailable AQP4-IgG testing using best available methods.

Exclusion of alternative diagnoses.

ANY of the following

Optic neuritis.
Acute myelitis.
Area postrema syndrome (otherwise unexplained hiccups or nausea and vomiting).
Acute brainstem syndrome.
Symptomatic narcolepsy or acute diencephalic clinical syndrome with NMOSD-typical diencephalic MRI lesions.
Symptomatic cerebral syndrome with NMOSD-typical brain lesions.

ANY of the following

CSF neurofilament light (NfL) is higher in MS than controls and correlates with disease activity; relapsing disease associated with higher CSF NfL (Martin et al.).
Combined biomarker profiles (eg, NfL + CHI3L1 or multiplex CSF+serum panels) improve discrimination of MS subtypes and prediction of progression; single biomarkers are less accurate than combinations (Gil-Perotin et al., Kodosaki et al.).
Serum NfL percentiles and Z-scores can identify individuals at risk for future activity and may decrease with certain disease-modifying therapies (Benkert et al.).

ANY of the following

CSF OCB testing is recommended in certain scenarios (insufficient clinical/MRI evidence, atypical presentations, progressive onset, or populations with lower MS prevalence) and CSF must be paired with serum to demonstrate CSF-specific OCBs.
MOG-IgG testing: use cell-based assays on serum; avoid routine testing in progressive disease because of very low pre-test probability; consider retesting during acute attacks or after treatment windows if suspicion persists despite an initial negative test.
AQP4-IgG testing: use cell-based serum assays when possible; confirmatory testing is recommended if lower-sensitivity methods are used and testing at specialized laboratories may be required for optimal performance.

Operational note: clinicians and laboratories should follow the Lab Benefit Program reimbursement guidance and applicable billing and claims payment policies; claims may be denied or recouped if coding/billing guidelines or reimbursement policies are not followed.

ALL of the following

Multiple peer-reviewed studies and guideline references are cited in the full policy to support clinical context and testing utility.
Revision history: policy established and reformatted with new policy number effective 2/13/2026.

Procedure codes - billing reference

Applicable CPT/HCPCS procedure codes are provided for billing reference. These codes are for general reference and may not be all-inclusive; always confirm coding and payment rules before billing. If appropriate coding/billing guidelines are not followed, claims may be denied or payments recouped.

83520 — Immunoassay for analyte other than infectious agent antibody or infectious agent antigen; quantitative, not otherwise specified.
83884 — Neurofilament light chain (NfL).
83916 — Oligoclonal immune (oligoclonal bands).
84182 — Protein; Western Blot, with interpretation and report, blood or other body fluid, immunological probe for band identification, each.
86051 — Aquaporin-4 (NMO) antibody; enzyme-linked immunosorbent immunoassay (ELISA).
86052 — Aquaporin-4 (NMO) antibody; cell-based immunofluorescence assay (CBA), each.
86053 — Aquaporin-4 (NMO) antibody; flow cytometry (FACS), each.
86362 — Myelin oligodendrocyte glycoprotein (MOG-IgG1) antibody; cell-based immunofluorescence assay (CBA), each.
86363 — Myelin oligodendrocyte glycoprotein (MOG-IgG1) antibody; flow cytometry (FACS), each.
88341 — Immunohistochemistry or immunocytochemistry, per specimen; each additional single antibody stain procedure.
88342 — Immunohistochemistry or immunocytochemistry, per specimen; initial single antibody stain procedure.

inv-12: CSF-specific oligoclonal bands (OCBs) — role in diagnosis and substitution for dissemination in time

DefinitionCSF-specific oligoclonal bands are immunoglobulin bands unique to CSF that, in the absence of atypical CSF findings, support a diagnosis of MS and can substitute for dissemination in time.

Clinical roleCan be used to make a diagnosis of MS when clinical or MRI evidence is insufficient and no better explanation exists.

Testing requirementCSF must be paired with a serum sample to demonstrate that OCBs are unique to the CSF.

inv-13: MOG-IgG testing — recommended specimen and assay (serum, cell-based assays, FACS)

Recommended specimenSerum is the recommended specimen of choice for MOG-IgG testing.

Preferred assayCell-based assays targeting full-length human MOG (IgG-specific), including FACS, are the gold standard.

Assays not recommendedImmunohistochemistry, peptide ELISA, and Western blot are NOT recommended due to lower specificity/sensitivity.

Timing of testingSerum MOG-IgG concentrations are highest during acute attacks and when not receiving immunosuppressive therapy; retest during acute attack or treatment-free intervals if suspicion remains after a negative result.

inv-14: AQP4-IgG testing — recommended serum cell-based assays; note on ELISA/indirect methods

Recommended assayCell-based serum assays (microscopy or flow cytometry-based) are recommended for optimal sensitivity and specificity for AQP4-IgG.

Lower-sensitivity methodsELISA and indirect immunofluorescence have lower sensitivity; interpretative caution and confirmatory testing are recommended when these are used.

ReferralSamples may need referral to specialized laboratories for cell-based assay testing to optimize detection.

inv-15: Laboratory-developed test (LDT) — definition and regulatory context under CLIA '88

DefinitionLaboratory-developed tests (LDTs) are tests developed and validated by individual laboratories and performed in-house.

Regulatory contextLDTs are regulated by CMS as high-complexity tests under CLIA '88.

FDA statusLDTs are not approved or cleared by the U.S. Food and Drug Administration; FDA clearance is not currently required for clinical use.

inv-16: AQP4Ab ELISA (KRONUS) — FDA-approved semiquantitative assay description

Test nameKRONUS Aquaporin-4 Autoantibody (AQP4Ab) ELISA Assay

Regulatory statusFDA-approved (2016) for semiquantitative determination of autoantibodies to Aquaporin-4 in human serum.

Intended useMay be useful as an aid in the diagnosis of NMO/NMOSD but is not to be used alone; should be used with other clinical, laboratory, and radiological findings.

Policy reformatted and reorganized; content transferred to new template with new reimbursement policy number.