Vocal cord paralysis as a manifestation of myasthenia gravis with anti-MuSK antibodies

Dear Editor:

Patients with myasthenia gravis with antibodies to muscle-specific tyrosine kinase (anti-MuSK antibodies) represent a subgroup whose characteristics differentiate them from patients with acetylcholine receptor antibodies. This disorder is predominant in women, and age of onset is typically around 40 years. Patients develop predominantly facial and bulbar symptoms and experience frequent episodes of respiratory failure. They also exhibit poor tolerance for or lack of response to cholinesterase inhibitors.¹ Many patients experience rapid decline at onset and plasmapheresis is the treatment of choice in some hospitals. However, long-term prognosis resembles that of patients presenting myasthenia gravis with acetylcholine receptor antibodies.²

We present the case of a 46-year-old woman with no relevant medical history. She was admitted to the emergency department due to a 3-week history of dyspnoea with moderate exertion, predominantly in the morning, associated with dysphonia and stridor. She presented no other bulbar or ocular symptoms and no limb weakness.

General examination yielded normal results. Neurological examination revealed dysphonic voice associated with stridor, which worsened with repeated efforts. It also revealed predominantly right-sided eyelid ptosis which also intensified with repetition. No ophthalmoparesis or any other pathological signs were observed during the examination. Direct laryngoscopy revealed vocal fold abduction paresis that had reduced the abduction angle by 20°. A Tensilon^® test yielded negative results.

Results from the blood test, including acetylcholine receptor antibodies and calcium channel antibodies, were negative. The patient tested positive for anti-MuSK antibodies: 9.0 nmol/L (normal <0.05). Chest radiography and CT were normal. Electromyography (EMG) showed increased jitter in the frontalis muscle and low-frequency repetitive nerve stimulation of the orbicularis oculi showed a significant decrementing response.

Treatment with pyridostigmine at doses up to 180 mg/day did not improve symptoms and was poorly tolerated, causing diarrhoea and nausea. We prescribed prednisone at a dose of 1 mg/kg/day, which lessened symptoms until the patient was asymptomatic. The dose was reduced to 20 mg/day during follow-up, as greater decreases can lead to stridor, eyelid ptosis, and diplopia.

Vocal cord paralysis can be due to multiple disorders, some of which are neurological. Paralysis causes an increased resistance to airflow, and therefore dysphonia and stridor, as a consequence of weakness of the posterior cricoarytenoid muscles. Although this is rare, vocal cord paralysis may indicate onset of myasthenia gravis. Despite the low frequency of anti-MuSK antibody myasthenia gravis, several cases with a similar effect have been reported^3,4 because this type of myasthenia gravis mainly affects bulbar muscles. In the cases described to date, including ours, paralysis affects abduction and not adduction, and therefore the condition would preferentially affect posterior cricoarytenoid muscles.

Presence of dysphonia and stridor that intensify with fatigue should lead us to suspect bulbar myasthenia gravis. Lack of response to cholinesterase inhibitors and negative results from a test for acetylcholine receptor antibodies would not rule out this possibility. We have seen that these results are negative in cases of myasthenia gravis with anti-MuSK antibodies. Neurophysiological studies yield data typical of neuromuscular junction disease, including a decrementing response to low-frequency repetitive nerve stimulation and pathological jitter. Another entity which may cause bulbar symptoms with fatigue is Eaton-Lambert syndrome, but autonomic symptoms in these patients are usually pronounced (arterial hypertension, dry mouth, sexual dysfunction, etc.). Furthermore, during neurophysiological examination, high-frequency repetitive nerve stimulation shows facilitation, although the phenomenon in Eaton-Lambert syndrome can be indistinguishable from that of myasthenia gravis.

In myasthenia gravis with anti-MuSK antibodies, atrophy of facial and tongue muscles has been described in magnetic resonance studies.⁵ However, this finding is normally reported when the disease is at an advanced stage and its diagnostic utility remains uncertain.

Early diagnosis of myasthenia gravis with anti-MuSK antibodies eliminates unnecessary tests and prevents delays in treatment of what may be a life-threatening condition; a patient can die of respiratory failure if the vocal cords remain closed.