From the Guidelines
To rule out myasthenia gravis, I recommend ordering acetylcholine receptor antibody testing (AChR antibodies) as the initial laboratory test, which has high specificity and is positive in about 85-90% of patients with generalized myasthenia gravis. This is based on the understanding that antibody production against acetylcholine in myasthenia gravis blocks neurotransmission to muscle fibers, causing fatigue and decreased muscle response 1.
When considering the diagnosis of myasthenia gravis, it's crucial to understand that the condition depends on the accuracy of diagnostic tests such as repetitive nerve stimulation (RNS) to affected muscles, as mentioned in the study by 1. However, if the response to RNS is normal and there is still a high suspicion of a neuromuscular junction disorder, then single-fiber electromyography (SFEMG) of at least one symptomatic muscle is recommended, as it can help identify abnormal jitter or impulse blockade 1.
In terms of laboratory tests, the following should be considered:
- Acetylcholine receptor antibody testing (AChR antibodies)
- Muscle-specific kinase antibodies (MuSK) if AChR antibodies are negative
- Low-density lipoprotein receptor-related protein 4 (LRP4) antibodies for remaining seronegative cases
- Anti-striated muscle antibodies to support the diagnosis, particularly in patients with thymoma
- Complete blood count, comprehensive metabolic panel, thyroid function tests, and erythrocyte sedimentation rate to rule out conditions that can mimic or exacerbate myasthenia gravis
These laboratory tests should be complemented by clinical evaluation, including neurological examination focusing on fatigable muscle weakness, and may need to be supplemented with electrophysiological studies such as repetitive nerve stimulation or single-fiber electromyography for definitive diagnosis, as suggested by the study 1. Chest imaging (CT or MRI) is also important to evaluate for thymoma, which is associated with myasthenia gravis in about 10-15% of cases.
From the Research
Laboratory Tests for Myasthenia Gravis
To rule out myasthenia gravis, several laboratory tests can be ordered, including:
- Radioimmunoprecipitation assays (RIPA) to detect autoantibodies against the acetylcholine receptor (AChR) 2, 3, 4
- Cell-based assays (CBAs) to detect autoantibodies against AChR, muscle-specific kinase (MuSK), and low-density lipoprotein receptor-related protein 4 (LRP4) 2
- Tests to detect autoantibodies against other targets, such as agrin, Kv1.4 potassium channels, collagen Q, titin, the ryanodine receptor, and cortactin 2, 3, 4
- Measurement of antibodies to omega-conotoxin receptor in Lambert Eaton Myasthenic Syndrome (LEMS) 3, 4
Specific Antibody Tests
The following specific antibody tests can be ordered:
- Anti-acetylcholine receptor antibody (AChR) test to diagnose AChR-MG 5, 6
- Anti-muscle specific kinase antibody (MuSK) test to diagnose MuSK-MG 5, 6
- Anti-low-density lipoprotein receptor-related protein 4 (LRP4) antibody test to diagnose LRP4-MG 2, 6
- Striated antibody tests, such as anti-titin, anti-ryanodine, anti-agrin, and anti-rapsyn, although these are less frequent and clinically less useful 3, 4