Myasthenia Gravis: Effects on the Middle Ear Muscles and Outer Hair Cells

Myasthenia gravis (MG) is the most common autoimmune disorder affecting the neuromuscular junction. Motor neurons tell muscles to contract by releasing the neurotransmitter acetylcholine, which binds to postsynaptic acetylcholine receptors and ultimately triggers the movements of myosin/actin protein chains in muscle fibers. In most patients with MG, the body produces harmful antibodies that destroy acetylcholine receptors (autoantibodies), disrupting communication between motor neurons and muscles. This chronic disorder is characterized by general weakness and fatigue of skeletal muscles such as in the arms and legs, as well as difficulty swallowing and speaking, and shortness of breath. Double vision due to weakness of the eye muscles (ocular myasthenia), which are in almost constant use, is often the first symptom, along with a drooping of one or both eyelids (ptosis). The worldwide prevalence of MG ranges from about five-to-35 per 100,000 people.1 Average age of onset varies but tends to peak in young adulthood for women (under 40 years old) and in older men (over 60 years old).ShutterstockLike most autoimmune disorders, the etiology of the attacks responsible for MG is complicated and remains poorly understood. The over-secretion of certain types of white T-cells by the thymus leads to an upregulation of cytokines that promote chronic inflammation at the neuromuscular junction, triggering the production autoantibodies by white B-cells. Two-thirds of MG patients exhibit enlarged thymus glands (thymic hyperplasia), and up to one-third have malignant tumors in the thymus (thymomas). Thymoma patients may develop MG as a side-effect of the immune response targeting the tumor, which spreads into surrounding neuromuscular junctions.2 There is currently no cure for MG, but treatments such as the drug pyridostigmine, a cholinesterase inhibitor that helps maintain higher concentrations of acetylcholine, can help manage symptoms and improve quality of life. MG AND HEARING LOSS MG can lead to hearing difficulties, including hearing loss, tinnitus, and hyperacusis. As described, MG is characterized by the destruction of acetylcholine receptors. In the ear, these receptors are found in the neuromuscular junctions of the middle ear muscles (tensor tympani and stapedius), and in the synapses between medial olivocochlear (MOC) efferent fibers and cochlear outer hair cells (OHCs). Mediated by the involuntary contraction of middle ear muscles, the acoustic reflex plays a well-known otoprotective role. 84% of patients diagnosed with MG exhibited abnormal stapedial muscle fatigue, presumably making them more vulnerable to noise-induced hearing loss and its consequences, including tinnitus and hyperacusis.3 In MG patients, acoustic reflex amplitudes were reduced to less than 10% of baseline following continuous stimulation for 120 seconds, whereas the maximum decay in control subjects was only 50%.4 The role of the MOC efferent system is to decrease OHC electromotility (i.e., decrease cochlear amplifier gain), by hyperpolarizing the OHC membrane.5 As with the acoustic reflex, this has been shown to have a significant otoprotective role, as well as improving frequency selectivity and sound detection in noise.6 A weakened MOC efferent system, measured by the reduced contralateral suppression of distortion product otoacoustic emissions (DPOAEs), was demonstrated in MG patients,7 again presumably making them more vulnerable to noise-induced hearing loss. Additionally, prolonged exposure to MG antibodies was shown to destroy the OHC basal membrane, leading to OHC apoptosis and to reduced DPOAEs and TEOAEs (transient evoked OAEs), especially at high frequencies.8–10 This high frequency hearing loss could, in turn, lead to tinnitus and hyperacusis.11,12 More research is needed on the prevalence and progression of hearing problems with MG, and on the potential efficacy of treatments such as pyridostigmine. A comprehensive audiologic examination is warranted in patients suspected or recently diagnosed with MG. This should include measurements of acoustic reflex amplitudes and their decay, and of DPOAEs and/or TEOAEs, including assessment of the MOC efferent reflex pathway via the suppression of OAEs with contralateral sound. Testing should be performed to the highest frequencies possible, to accurately assess the progression of hearing loss associated with MG, which usually begins at high frequencies. OAEs are a particularly useful tool because they are often more sensitive to OHC loss than the audiogram. However, the audiogram can be measured to 16–20kHz, whereas DPOAE testing is currently limited to about 8kHz, and TEOAE testing to about 4kHz. It is also important for MG patients to be appropriately counseled on the importance of hearing protection and conservation, given their increased vulnerability to noise-induced injury. Informing MG patients to make a conscious effort to reduce exposure to loud music and noise and follow proper precautions such as wearing hearing protection in noisy environments is key to preserving the auditory structures as best as possible given their weakened acoustic and MOC reflexes, and increasingly vulnerable OHCs. Annual or bi-annual hearing evaluations should be implemented as a component of the MG treatment plan and must aim to monitor hearing status and its potential deterioration, including complaints of tinnitus and hyperacusis.