Electrodiagnostic Evaluation of Neuromuscular Junction Disorder

Continuing Education Activity

Although not often performed, electrodiagnostic testing, which includes nerve conduction studies, needle electromyography, and repetitive nerve stimulation, remains the gold standard for diagnosing neuromuscular disorders. This activity describes the invaluable electrodiagnostic findings of nerve conduction studies, needle electromyography, and repetitive nerve stimulation and highlights the role of the interprofessional team.

Objectives:

• Identify the indications for electrodiagnostic testing in a patient with a neuromuscular disorder.
• Assess the nerve conduction study findings in a patient with a neuromuscular disorder.
• Evaluate the electromyographic findings in a patient with neuromuscular disorders.
• Communicate the importance of collaboration of the interprofessional team to enhance the delivery of care for patients with neuromuscular disorders.

Introduction

Neuromuscular junction disorders are a group of conditions that cause muscle weakness. Their etiology can be autoimmune, congenital, metabolic, or toxic mediated. The 3 most common neuromuscular junction disorders are myasthenia gravis, Lambert-Eaton myasthenic syndrome (LEMS), and botulism. The primary pathology is impaired neurotransmission at the interface (synapse) between the nerve ending and the skeletal muscle fiber. In myasthenia gravis, pathology occurs at the postsynaptic membrane.[1] In Lambert-Eaton myasthenic syndrome and botulism, the presynaptic membrane is affected.[1][2] Neuromuscular Junction disorder patients present with complaints of muscle fatigue and weakness that fluctuate with episodes of worsening after activity. The sensory system is unaffected, as sensory nerves do not have a neuromuscular junction. Patients present with proximal greater than distal muscle weakness. It is common to receive complaints about bulbar or extraocular muscle weakness. Myasthenia gravis patients frequently present with bulbar weakness and limb weakness. It is important to investigate if the patient has a history of thymoma.[3] LEMS patients less commonly present with bulbar weakness but have diffuse proximal limb weakness. LEMS has a strong correlation with small cell carcinoma.[4][5] Botulism is a rare condition caused by a toxin produced by Clostridium botulinum. In the United States, most cases are seen in infants.[6] 

Indications

The diagnosis of neuromuscular junction disorder derives from a thorough history and physical examination, electrodiagnostic studies with repetitive nerve stimulation (RNS), exercise testing, and single-fiber EMG (SFEMG).[7] SFEMG testing is the gold standard for neuromuscular junction study with a sensitivity of up to 99%.[8] Anticholinesterase medication should be stopped 8 to 24 hours before performing the study.[2]

Contraindications

There are few absolute contraindications in performing electrodiagnostic studies in neuromuscular junction disorder. Needle EMG is contraindicated in those with severe bleeding disorders.[9] Needles should also never be inserted into areas of active soft tissue infection. NCS is contraindicated in patients with implanted cardiac defibrillators or if connected to external defibrillators. Patients should be screened for pacemakers, and electrical stimulation should not be performed directly on or near the device. 

Technique or Treatment

Before performing any diagnostic study, a comprehensive review of the patient’s history, clinical course, and a complete physical examination are necessary. The diagnostician informs the patient of the indications and provides an overview of their studies. The diagnostician must thoroughly explain the risks and benefits of the exam to the patient and obtain informed consent. A routine motor and sensory nerve conduction study should first be conducted to ensure no other nerve pathology exists and that the clinician can interpret the RNS results. RNS involves supramaximal motor nerve stimulation 5-10 times at 3 Hz to determine compound muscle action potential (CMAP) amplitude decrement. The 4th CMAP amplitude is compared with the first. A decrement of >10% is significant. RNS study should ideally be performed on the proximal and most affected muscle to increase sensitivity. However, this may not be possible or easily accomplished because of limitations in immobilizing the recording electrodes and the tested muscle. Limb and muscle movement during the test can alter the recording electrode, leading to inaccurate results. The limb temperature should be kept warm at 32 degrees Celsius. Colder temperature leads to increased amplitudes, prolonged latencies, slowed conduction velocities on NCS, and decreased CMAP decrement on RNS, leading to inaccuracy.[10]

Exercise testing is part of the RNS study routine to determine post-exercise facilitation and exhaustion. If no significant decrement is observed (>10%) with baseline test, a 1-minute exercise follows, and RNS is repeated at 1-minute intervals for 3 to 4 minutes to look for decrement due to post-exercise exhaustion. The patient is finally instructed to perform maximal isometric contraction of the tested muscle for 10 seconds. RNS is then performed at a 1-minute interval for 5 minutes to look for amplitude increment due to post-exercise facilitation and exhaustion. Single-fiber EMG is the most sensitive test for a patient suspected of neuromuscular junction disorder. The exam is proven to be safe, however, technically challenging for both the patient and the physician performing it. It requires experience and technical knowledge.[11][12] To perform a single-fiber EMG (SFEMG), you need a contracted single-fiber electromyography needle or a facial concentric needle with a small recording surface.[13] SFEMG study looks for variations in the action potential time interval amongst the muscle fibers from the same motor unit, called a jitter.[14] Jitter is the mean consecutive difference (MCD) measurement calculated between the triggered and second single muscle fiber action potentials. Most contemporary EMG machines have software that automatically creates the MCD calculation for you. The study is abnormal if the mean jitter value exceeds the upper limit of the normal value.[11][12]

Complications

Complications in performing electrodiagnostic studies are uncommon when observing proper precautions. There is a small risk of bleeding and infection with needle studies.

Clinical Significance

Motor Nerve Conduction Studies

Since the myelin is unaffected in an NMJ disorder, motor nerve conduction velocities are normal. However, amplitudes may be affected, and they can assist in differentiating myasthenia gravis from Lambert-Eaton myasthenic syndrome. CMAP decreases in the patient with Lambert-Eaton. Meanwhile, in myasthenia gravis, CMAP is within normal limits. 

Sensory Nerve Conduction Studies

The neuromuscular junction is not present in sensory nerves; therefore, the sensory nerve conduction study is normal.

Repetitive Nerve Stimulation/Exercise Testing

Normal subjects have no amplitude decrement between the first and the succeeding CMAP. However, a decrement of more than 10% between the first and the fourth stimulation can be appreciated in patients with neuromuscular junction disorder.[13] In myasthenia gravis, the baseline CMAP amplitude decrement is observed more than 70% of the time with RNS in generalized myasthenia gravis. Not uncommonly, no decrement is appreciated on RNS of distal muscles. However, a significant decrement is observable after a 1-minute exercise. Post-exercise repair or facilitation is also observable following a brief 10-second maximum isometric contraction, followed by a decrement in 2 to 5 minutes post-exercise due to post-exercise exhaustion.[15] On the other hand, with Lambert-Eaton myasthenia syndrome, baseline CMAP amplitude decrement is usually noted. After a brief 10-second maximum isometric muscle contraction, post-exercise facilitation of up to 200% increase in CMAP amplitude is typical. In 2 to 5 minutes, the clinician should note post-exercise exhaustion. Other neurologic disorders that can also show CMAP decrement on RNS include motor neuron disease, conditions where ongoing denervation and reinnervation result in immature nerve endings/neuromuscular junction, and myopathies. 

Single Fiber EMG

Single-fiber EMG reveals increased jitter and blocking in neuromuscular junction disorder. There is marked prolongation in jitter value, with MCD of more than 100 microseconds.[11] It is highly sensitive in the diagnosis of NMJ disorder but is not specific to myasthenia gravis. Pathologic conditions that involve reinnervation and, hence, immature nerve endings also show increased jitter. Due to the test's high sensitivity, neuromuscular junction disorder can be ruled out with a normal SFEMG study of a weak muscle.[16]

Late Responses

H-reflexes and F-reflexes are not routinely included in a neuromuscular junction study as they do not provide additional useful information.

Needle EMG

For a neuromuscular junction study, all weak muscles in the patient should be examined in the needle EMG portion of the test. During the exam, the diagnostician may notice unstable MUAPs with normal recruitment. Most Neuromuscular junction disorders do not show abnormal spontaneous activity except for botulism.[17] CMAP decrement on RNS in patients with muscle denervation or myotonic discharge findings on needle EMG study does not signify NMJ disorder.

Enhancing Healthcare Team Outcomes

Neuromuscular junction disorders are a condition often seen in the outpatient setting. Patients frequently complain of muscular proximal weakness in the extremities with/without bulbar and extraocular findings. Electrodiagnostic studies should follow a comprehensive history and a physical exam. It is essential to take an interprofessional team, including physicians, physical therapists, occupational therapists, social workers, and case managers, who can work together to provide aggressive, multifaceted rehabilitation care to improve a patient's functional status.[18][19] 

Review Questions

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• Comment on this article.

References

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Juel VC. Single fiber electromyography. Handb Clin Neurol. 2019;160:303-310. [PubMed: 31277856]

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Disclosure: Parini Patel declares no relevant financial relationships with ineligible companies.

Disclosure: Thomas Pobre declares no relevant financial relationships with ineligible companies.