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Test ID: MGRM Myasthenia Gravis (MG) Evaluation with MuSK Reflex, Serum

Useful For

Diagnosis for autoimmune myasthenia gravis (MG) in adults and children

 

Distinguishing autoimmune from congenital MG in adults and children

 

Establishing a quantitative baseline value that allows comparison with future levels if weakness is worsening

Profile Information

Test ID Reporting Name Available Separately Always Performed
MGRMI MG Interpretive Comments No Yes
ARBI ACh Receptor (Muscle) Binding Ab Yes Yes
STR Striational (Striated Muscle) Ab, S Yes Yes
ARMO ACh Receptor (Muscle) Modulating Ab No Yes

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
MUSK MuSK Autoantibody, S Yes No
GD65S GAD65 Ab Assay, S Yes No
GANG AChR Ganglionic Neuronal Ab, S No No
VGKC Neuronal (V-G) K+ Channel Ab, S No No
CRMWS CRMP-5-IgG Western Blot, S Yes No

Testing Algorithm

If acetylcholine receptor (AChR) modulating antibodies are ≥90% and striational antibodies are ≥1:120, then ganglionic AChR neuronal autoantibody, glutamic acid decarboxylase autoantibody, neuronal voltage-gated potassium channel autoantibody, and collapsin response-mediator protein-5 (CRMP-5)-IgG Western blot will be performed at an additional charge.

 

If AChR-binding antibodies are ≤0.02 and AChR-modulating antibodies are ≤20%, then muscle-specific kinase (MuSK) autoantibody will be performed at an additional charge.

 

See Myasthenia Gravis Evaluation with MuSK Reflex Algorithm in Special Instructions.

Reporting Name

MG Evaluation with MuSK Reflex, S

Specimen Type

Serum


Specimen Required


Patient Preparation: Patient should have no general anesthetic or muscle-relaxant drugs in the preceding 24 hours.

Container/Tube:

Preferred: Red top

Acceptable: Serum gel

Specimen Volume: 3 mL


Specimen Minimum Volume

2 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Serum Refrigerated (preferred) 28 days
  Frozen  28 days
  Ambient  72 hours

Clinical Information

Fatigable weakness due to impaired synaptic transmission at the neuromuscular junction is characteristic of myasthenia gravis (MG). The diagnosis is made by clinical and electromyographic criteria. Positive autoimmune serology must be interpreted in the clinical and electrophysiological context and response to anticholinesterase medication. Most cases are autoimmune and are caused by IgG autoantibodies binding to critical postsynaptic membrane molecules (nicotinic acetylcholine receptor or its interacting proteins, such as muscle-specific kinase: MuSK).(1) Autoantibody detection frequency is lowest in patients with weakness confined to extraocular muscles (71% muscle acetylcholine receptor: AChR binding). Mayo Clinic's first-line serological evaluation detects muscle AChR antibody in 92% of nonimmunosuppressed patients with generalized weakness due to MG. In adults with MG there is at least a 20% occurrence of thymoma or other neoplasm. If acetylcholine receptor (AChR) modulating antibodies are greater than or equal to 90% and striational antibodies are 1:120 or greater, then there is an increased risk of thymoma, and AChR ganglionic neuronal autoantibody, glutamic acid decarboxylase autoantibody, neuronal voltage-gated potassium channel autoantibody, and collapsin response-mediated response-5-IgG may also be detected in that paraneoplastic context.(2)

 

MuSK antibody is detectable in more than one-third of those seronegative for muscle AChR antibody (<4% of all patients).(3-4) Physiologically, MuSK is involved in integrating and stabilizing AChR clusters in the motor endplate. MuSK is activated when the nerve-derived proteoglycan agrin binds to its receptor, lipoprotein-related protein 4 (LRP4). Antibodies to LRP4 itself have been described in rare patients.(1) Females are generally affected by autoimmune MuSK MG more often than males. Onset can occur at any age (pediatric to elderly). Patients may derive limited benefit from anticholinesterase medication. The thymus is normal, and patients are generally not benefited by thymectomy. Antibody-lowering therapies are effective. Bulbar, facial, and respiratory weakness are prominent, and crises are common.(1,3,4)

 

Six percent of nonimmunosuppressed patients with generalized MG lack demonstrable AChR or MuSK antibodies (double seronegative). However, as in autoimmune AChR MG and MuSK MG, testing for common organ-specific and nonorgan-specific autoantibodies is a valuable ancillary investigation in evaluating seronegative acquired generalized MG. General serological testing, coupled with family or personal history, will disclose autoimmune phenomena in 77% of those cases.(5) These disorders may include thyroid disease, type 1 diabetes, vitiligo, premature greying, rheumatoid arthritis, or lupus. Objective improvement in strength following a therapeutic trial of plasmapheresis or intravenous immune globulin would justify consideration of long-term immunosuppression.

Reference Values

ACETYLCHOLINE RECEPTOR (MUSCLE) BINDING ANTIBODY

≤0.02 nmol/L

 

ACETYLCHOLINE RECEPTOR (MUSCLE) MODULATING ANTIBODIES

(reported as __% loss of AChR)

0%-20% 

 

STRIATIONAL (STRIATED MUSCLE) ANTIBODIES

<1:120

 

MUSCLE-SPECIFIC KINASE (MuSK) AUTOANTIBODY

≤0.02 nmol/L

 

GLUTAMIC ACID DECARBOXYLASE (GAD65) ANTIBODY ASSAY

≤0.02 nmol/L

 

COLLAPSIN RESPONSE-MEDIATOR PROTEIN-5-IgG (CRMP-5-IgG) WESTERN BLOT

Negative

 

GANGLIONIC ACETYLCHOLINE RECEPTOR (ALPHA3) AUTOANTIBODIES

≤0.02 nmol/L

 

NEURONAL VOLTAGE-GATED POTASSIUM CHANNEL (VGKC) AUTOANTIBODY

≤0.02 nmol/L

Interpretation

A positive result, in the appropriate clinical context, confirms the diagnosis of autoimmune myasthenia gravis, with or without thymoma.

 

Seropositivity justifies consideration of immunotherapy.

Clinical Reference

1. Li Y, Arora Y, Levin K: Myasthenia gravis: Newer therapies offer sustained improvement. Cleve Clin J Med 2013 Nov;80(11):711-721

2. Vernino S, Lennon VA: Autoantibody profiles and neurological correlations of thymoma. Clin Cancer Res 2004 Nov 1;10(21):7270-7275

3. Skjei KL, Lennon VA, Kuntz NL: Muscle specific kinase autoimmune myasthenia gravis in children: A case series. Neuromuscul Disord 2013 Nov;23(11):874-882

4. Hoch W, McConville J, Helms S, et al: Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies. Nat Med 2001 Mar;7(3):365-368

5. Chan KH, Lachance DH, Harper CM, Lennon VA: Frequency of seronegativity in adult-acquired generalized myasthenia gravis. Muscle Nerve 2007 Nov;36(5):651-658

Day(s) and Time(s) Performed

ACh receptor (muscle) binding antibody:

Monday through Friday;11 a.m., 6 p.m., 10 p.m.

Saturday; 6 a.m.

Sunday; 6 a.m., 10 a.m.

 

ACh receptor (muscle) modulating antibodies:

Monday through Thursday; 2 p.m.

Saturday; 8 a.m.

 

Striational (striated muscle) antibodies:

Monday through Friday; 4 a.m., 3 p.m.

Saturday; 6 a.m.

 

CRMP-5-IgG Western blot:

Monday, Wednesday, Friday; 8 a.m.

 

AChR ganglionic neuronal antibody:

Monday through Friday; 11 a.m., 6 p.m.

Saturday; 6 a.m.

Sunday; 6 a.m.

 

Neuronal VGKC autoantibody:

Monday through Friday; 11 a.m., 6 p.m.

Saturday; 6 a.m.

Sunday; 6 a.m.

 

GAD65 antibody assay:

Monday through Friday; 6 a.m.,4 p.m.

 

MUSK autoantibody assay:

Tuesday, Thursday; 6 a.m.

Analytic Time

3 days

CPT Code Information

83519 x 2

83520

83519 x 3 (if appropriate)

84182 (if appropriate)

86341 (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
MGRM MG Evaluation with MuSK Reflex, S 53706-8

 

Result ID Test Result Name Result LOINC Value
8338 ACh Receptor (Muscle) Binding Ab 11034-6
8879 ACh Receptor (Muscle) Modulating Ab 30192-9
8746 Striational (Striated Muscle) Ab, S 94817-4
37213 MG Interpretive Comments 69048-7

Method Name

ARBI, ARMO, GANG, VGKC: Radioimmunoassay (RIA)

STR: Enzyme Immunoassay (EIA)

CRMWS: Western Blot

Forms

If not ordering electronically, complete, print, and send a Neurology Specialty Testing Client Test Request (T732) with the specimen.

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.
Mayo Clinic Laboratories | Neurology Catalog Additional Information:

mml-Neuroimmunology, mml-Neuromuscular, mml-Pediatric, mml-Neuro-ophthalmology, mml-Neuroimmunology-Evals