Clarifications to “Isolated bilateral facial palsy as the initial presenting manifestation of generalized myasthenia gravis preceding myasthenic crisis”: The importance of not forgetting single-fiber electromyography

Dear Editor,

We consider it extremely important to make some clarifications regarding our manuscript, published online in August 2025 in Neurologia.¹ In the last paragraph of page 2, the following statement appears: “It is paramount to ask for repetitive nerve stimulation, AChR antibodies, and other antibodies (MuSK, LRP4, and cortactin) in case of a strong clinical suspicion of myasthenia gravis for diagnostic confirmation. Early recognition of this clinical scenario could help achieve prompt diagnosis and proper treatment before a myasthenic crisis appears”.

Because of the lack of resources in rural India, we did not mention in that paragraph that single-fiber electromyography (SFEMG) should also be requested. Still, we must not forget that this represents an essential neurophysiological test to perform on patients with myasthenia gravis (MG), if available.

MG constitutes a rare autoimmune neuromuscular disease characterized by fatigable and fluctuating weakness due to impaired neuromuscular transmission.^2,3 It is the most common neuromuscular transmission disorder. Its annual incidence is estimated to range from 7 to 23 cases per million population, while prevalence varies from 70 to 320 cases per million population.⁴

SFEMG, apart from repetitive nerve stimulation and autoantibody testing (e.g., anti-acetylcholine [anti-AChR] and anti-muscle-specific kinase [anti-MuSK] antibodies), plays a key role in diagnosing MG.^4–6 SFEMG has the highest sensitivity for demonstrating impairment of neuromuscular transmission like MG, and poses a higher negative predictive value for identifying patients who do not have MG,^4–7 including cases of suspected myasthenic crisis unveiling generalized MG.⁸ It is safe, but the performance of jitter measurements with single-fiber EMG electrodes or concentric-needle electrodes is technically demanding for both the patient and the neurologist or clinical neurophysiologist performing it, requiring considerable time and experience to develop the skills necessary to obtain quality recordings within a reasonable period of time.^7,9 Disposable, reasonably-priced SFEMG electrodes should be designed to permit recordings consistent with the original jitter analysis technique.⁹

Stålberg and Eskedt established SFEMG in the 1960s, and the study is of proven value in the diagnosis of neuromuscular disorders, especially MG.⁷ It usually requires the use of a specially contracted single-fiber EMG needle electrode or a facial concentric needle electrode with a small recording surface (25 μm), which is exposed at a port on the side of the electrode, 3 mm from the tip.⁷

The validity of the technique has been proven by examining a large number of MG patients. When a motor axon is depolarized, action potentials travel distally and excite the muscle fiber more or less at the same time.⁷ The variation in the time interval between the two action potentials of the same motor unit is called “jitter.” SFEMG measures the variation of this interpotential interval (jitter).^7,10

SFEMG also records action potentials from single muscle fibers (SFAPs), which permits measurement of fiber density (FD), a sensitive measure of reinnervation, and jitter, a sensitive measure of abnormal neuromuscular transmission.¹¹ With voluntary activation, jitter is measured between two SFAPs with acceptable amplitude and rise time. With activation by axon stimulation, jitter is measured between the stimulus and individual SFAPs.¹¹ It is important to identify and avoid the pitfalls of the technique due to unstable triggers and inconstant firing rates during voluntary activation and subliminal stimulation during axon stimulation.¹¹ Concentric needle electrodes and SFEMG have similar and very high sensitivity in detecting increased jitter, as in MG. However, jitter is also seen in ongoing reinnervation and some myopathic conditions.¹¹ With SFEMG, these can be identified by increased FD; however, FD cannot be measured with concentric needle electrodes, and conventional electromyography should be performed in muscles with increased jitter to detect neurogenic or myogenic abnormalities.¹⁰ It should be noted that jitter is also abnormal after injections of botulinum toxin.¹¹

In a single-blinded study of 100 consecutive patients with clinical suspicion of MG, the sensitivity of SFEMG in diagnosing MG was 98% (95% CI: 0.94–1.02), while the specificity was 70% (95% CI: 0.54–0.86), with a positive predictive value of 79% (95% CI: 0.74–0.79) and a negative predictive value of 97% (95% CI: 0.94–0.99).⁴ In another study, SFEMG of the extensor digitorum communis showed high abnormality in ocular MG, suggesting subclinical involvement not limited to the extraocular muscles.⁵ Moreover, abnormal orbicularis oculi SFEMG in patients with seronegative ocular MG has been shown to have a high predictive value for response to treatment.⁶

In particular, regarding the sensitivity/specificity (and the drawbacks) of standard tests used in the diagnosis of MG presenting with ocular symptoms, the edrophonium (tensilon) test has 80–90%/80–90% (cardiac monitoring mandatory), SFEMG 100%/85% (requires trained personnel and equipment), AChR-antibodies 55%/100% (high rate of false negatives in ocular myasthenia), rest test 50%/100% (high false negatives), and the ice-on-eyes test 90–95%/100% (may be less sensitive with complete ptosis).¹²

Of note, it has been recently demonstrated that using concentric needle jitter analysis has the potential to evaluate baseline and sequential disease severity in MG, improving the accuracy of MG diagnosis and monitoring of disease activity, and therefore improving MG patient care through better assessment and management.¹³

In short, if trained personnel and equipment are available and MG is strongly suspected, performing SFEMG is warranted, since it has a high negative predictive value in identifying patients without MG, and thus, for avoiding misdiagnosis and starting unnecessary MG therapies with significant potential secondary effects (e.g., anticholinesterase inhibitors, immunosuppressants [prednisone, azathioprine, mycophenolate mofetil, etc.], complement inhibitors [eculizumab, ravulizumab, and zilucoplan], B-cell inhibitors [rituximab {anti CD-20}, inebilizumab {anti CD-19}, mezagitamab {anti CD-38}, and satralizumab {IL-6 inhibitor}], neonatal Fc Receptor [FcRn] inhibitors [efgartigimod, rozanolixizumab, nipocalimab, and batoclimab], plasmapheresis, intravenous immunoglobulins, etc.).^3,14,15

CRediT authorship contribution statement

All authors contributed significantly to the creation of this manuscript; each fulfilled the criteria as established by the ICMJE.

Informed consent

Not applicable.

Funding

None declared.

Conflict of interest

The authors report no relevant disclosures.

Acknowledgments

J. Benito-León is supported by the National Institutes of Health (NINDS R01 NS39422 and R01 NS094607) and by Spain's Ministry of Science and Innovation through the Recovery, Transformation, and Resilience Plan (grants TED2021-130174B-C33, NETremor, PID2022-138585OB-C33, Resonate, and CPP2023-010465).