Laryngeal MG is Best Diagnosed with a Tensilon Test or Pyridostigmine Bromide Trial

Electrical improvement with a Tensilon test or pyridostigmine bromide trial are the recommended criteria for diagnosing laryngeal myasthenia gravis (MG), according to a retrospective case-control study in Journal of Voice.¹ Case and control patients exhibited no significant difference for seropositivity for anti-striational muscle antibodies.

Dysphonia and laryngeal issues may be the only manifestation of laryngeal MG | image credit: Дмитрий Симаков - stock.adobe.com

“Laryngeal MG is an underrecognized condition in the otolaryngology community owing in part to its seronegative presentation. Electrical improvement with a Tensilon test, or electrical or substantial symptomatic improvement with pyridostigmine bromide represents the most robust diagnostic criteria in these patients,” the authors wrote.

The study included 61 adult patients with laryngeal MG, 59% of which were previously misdiagnosed by another otolaryngologist. The patients had undergone laryngeal electromyography (LEMG) as part of their evaluation for neuromuscular junction dysfunction.

Repetitive nerve stimulation (RNS) can be used to support the diagnosis of laryngeal MG but not diagnose it, the study found.

All case patients with an electrically positive Tensilon test (80.6%) experienced symptom improvement. Sixty percent of those in the case group with a symptomatically positive Tensilon test (16.1%) improved following a treatment trial. RNS results were more likely to be positive in case patients than control patients. Cases had a higher severity of paresis in all laryngeal muscles with LEMG evaluation.

"Electrical improvement in laryngeal muscles tested with subsequent LEMG suggests that pyridostigmine bromide acts to increase the availability of acetylcholine at the postsynaptic cleft and improve voice quality and endurance," the authors stated.

A treatment trial was performed in patients in whom there was a high clinical suspicion for laryngeal MG. Sixty mg of pyridostigmine bromide were prescribed as follows: 1 tablet orally daily for 3 days, 1 tablet orally twice daily for 3 days, 1 tablet orally 3 times daily for 3 days, 1 tablet orally 4 times daily for 3 days, and then 1 tablet orally 5 times a day. The treatment trial period lasted for 4 to 6 weeks, and if the patient’s symptoms were relieved, the medication was continued at the maintenance dose and often switched to the long-acting preparation twice daily, and the patient was considered to have laryngeal MG.

Patients were aged 41 years on average at the time of their diagnosis. Among this case group, 73.8% were classified as professional voice users compared with 59.7% of control patients. Dysphonia (hoarseness) constituted the most prevalent laryngeal symptom across both case and control populations.

The researchers found that vocal fold paresis was more commonly reported in cases of laryngeal MG than controls, also noting that controls were more likely to exhibit vocal fold hypomobility compared with cases. "The difference between vocal fold paresis and hypomobility could be a difference in etiology, with vocal fold paresis arising from a neurologic etiology and vocal fold hypomobility denoting an undetermined etiology that could be of a neurogenic, mechanical, or malignant origin," the authors wrote.

In rare cases, the sole expression laryngeal complaints can be indicative of MG and may be the only prominent manifestation. For this reason, researchers recommend considering laryngeal disorder or dysphonia more carefully in patient diagnoses.²

“Patients with laryngeal MG have a focal manifestation of MG, which is currently not included in the classification system for MG," the authors wrote as they advocated for an increased clinical focus on treatment responses, patient characteristics and prognoses, and the underlying mechanisms of focal or seronegative manifestations in MG.

References

1. Mullen KD, Mozzochi KA, Hawkshaw MJ, Sataloff RT. Laryngeal myasthenia gravis in voice patients: clinical, serologic, and neuromuscular characterization of seronegative patients for antibodies against the acetylcholine receptor and muscle-specific kinase. Journal of Voice. 2024. doi:10.1016/j.jvoice.2024.09.038
2. Liu W, Xia Q, Men L., Wu Z, Huanga, R. Dysphonia as a primary manifestation in myasthenia gravis (MG): a retrospective review of 7 cases among 1520 MG patients. J Neurol Sci. 2007; 260:16-22. doi:10.1016/j.jns.2007.03.019