Laryngeal Manifestations of Myasthenia Gravis

Abstract

Laryngeal Manifestations of Myasthenia Gravis Jessica B. Howell (bio) and Jaime Eaglin Moore (bio) CARE OF THE PROFESSIONAL VOICE WHAT IS MYASTHENIA GRAVIS? Myasthenia Gravis (MG) is an autoimmune disease characterized by immunoglobulin G (IgG) autoantibodies against the postsynaptic acetylcholine receptor (Ach-R).1 This leads to a decrease in the number of receptors at motor end plates, subsequently causing a defect in neuromuscular transmission. This involves mainly skeletal muscle, and is manifested clinically as fatigability and weakness of voluntary muscle activity.2 This muscle weakness worsens with exercise.3 The most commonly affected muscles include extraocular muscles and the levator palpebrae.4 The incidence of MG is approximately 1:100,000, with women affected more than men (2:1).5 Elderly patients constitute roughly one third of all cases, with a peak incidence in men at ages sixty to seventy years; and in women there is a bimodal peak at twenty to forty years and around seventy years of age.6 WHAT ARE THE SYMPTOMS OF MYASTHENIA GRAVIS? Ocular muscles are most frequently affected with MG. The most common presenting complaints include diplopia (double vision) and ptosis (drooping eyelid). However, it is important to note that these symptoms can be absent in other forms of the disease, including bulbar (hindbrain) and laryngeal.7 Bulbar involvement is seen in 20% of MG patients, with symptoms including dysphagia (swallowing difficulty) and hypernasal speech secondary to fatigability of the esophageal and pharyngeal muscles.8 Isolated bulbar involvement typically occurs in late onset MG, which given its symptomatology, can easily be misdiagnosed. The diagnosis can be blurred further, as 40% of patients with late onset MG are seronegative, meaning titers of acetylcholine receptor antibodies (Ach-R) are undetectable.9 The otolaryngologic manifestations of MG include facial weakness, dysphagia, and dysphonia. Up to 27% of patients will present with swallowing and voice difficulties.10 Laryngeal involvement may lead to intermittent aphonia (loss of voice), hoarseness, vocal fatigue, hypernasality, inability to control pitch, slurred speech, monotone voice, and stridor (noisy breathing).11 The latter may be seen in the setting of respiratory failure, termed a myasthenic crisis. Respiratory failure secondary to MG is uncommon, occurring in 3- 8% of cases usually late in the disease.12 However, there have been case reports [End Page 355] of patients with initial presentation of myasthenic crisis. This subset of patients may require intubation and ventilatory support. Muscle relaxants used for rapid sequence intubation, such as succinylcholine, can cause prolonged paralysis in patients with MG; increasing time to extubation.13 HOW DO YOU DIAGNOSIS MYASTHENIA GRAVIS? The diagnosis of MG can be made with clinical, laboratory, pharmacologic, and electrophysiologic criteria. As previously discussed, patients present clinically with voluntary muscle weakness that improves with rest and worsens with exertion or throughout the day. Patients also can be diagnosed with a simple laboratory test aimed at identifying antibodies to acetylcholine receptors. Antibody levels greater than 0.2 nmol/L are deemed diagnostic.14 However, not all patients with MG have detectable levels of ACh-R antibodies, specifically those patients with isolated laryngeal and ocular forms.15 In these patients, muscle specific kinase antibodies (MuSK) can be used as an alternative.16 However, multiple studies have demonstrated that patients with laryngeal MG have undetectable anti-MuSK levels, as well.17 Anti-striated muscle antibodies are also found in some patient with MG and are associated with the presence of thymomas.18 If abnormal antibody levels are present, these levels cannot be used to monitor treatment success or progression of the disease. MG can be diagnosed with the "Tensilon test," which employs edrophonium, a short acting acetylcholinesterase inhibitor.19 Tensilon (Alliance Pharmaceuticals; Wiltshire, UK), which is no longer available, has now been replaced by Enlon (Mylan Teoranta; Rockford, IL). Edrophonium acts to prevent degradation of acetylcholine, increasing its ability to bind to remaining postsynaptic receptors. Objectively, this causes temporary improved muscle strength following intravenous administration and assessment can include electrophysiological testing.20 In generalized MG, this test has a sensitivity of 95%. However those with isolated ocular symptoms are less likely to demonstrate improvement. For those with laryngeal involvement, Tensilon testing was found to be positive in 97.4% of patients...