Craniofacial Muscles

11 Laryngeal Muscle Response to Neuromuscular Diseases and Speci fi c Pathologies
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11.5 Laryngeal Muscle Response to Myasthenia Gravis
Myasthenia gravis (MG) is an autoimmune neuromuscular disease that causes
fl uctuating muscle weakness and fatigue. The muscle weakness is caused by failure of
neuromuscular transmission, resulting from the binding of autoantibodies to proteins
involved in signaling at the NMJ. Antibodies bind to postsynaptic acetylcholine (ACh)
receptors, resulting in a reduction in the number of available ligand binding sites.
Normal repetitive nerve stimulation also leads to a successive decrease in the amount
of acetylcholine released presynaptically. The combination of fewer available binding
sites and reduced acetylcholine release at the motor end plate gives rise to the induced
muscle fatigue observed in patients with MG (Patel and Forsen 2001 ) .
Although any skeletal muscles can be affected by MG, the ocular, facial, oral, pharyngeal,
laryngeal, and respiratory muscles seem to be the most susceptible. The laryngeal
musculature was implicated in MG as early as 1914, when Edward Davis reported
to the Royal Society of Medicine a case of a 25-year-old woman who presented with
aphonia, dysphagia (Kluin et al. 1996 ), and nasal regurgitation (Davis 1914 ) . Mao et al.
(2001 ) reported a series of 40 patients who presented with hoarseness as their primary
complaint. Voice diagnostic testing including laryngeal videostroboscopy, EMG with
repetitive stimulation and Tensilon testing; radiographic evaluations were also conducted.
Stroboscopic observations revealed a fl uctuating unilateral or bilateral impairment
of vocal fold mobility. EMG detected evidence of NMJ abnormalities in all
subjects. Only one patient had evidence of AChR antibodies, but the authors reported
that many other abnormalities suggestive of autoimmune dysfunction were present.
Pyridostigmine therapy was initiated in 34 patients but was not tolerated in 4. Of the
remaining 30 patients, 23 reported improvement of symptoms. The authors concluded
that myasthenia gravis can present with symptoms con fi ned primarily to the larynx and
should be included in the differential diagnosis of dysphonia.
Of primary concern in human populations is weakness of laryngeal and pharyngeal
musculature leading to ineffective swallowing with poor airway protection. This
situation may be further compounded by a poor cough as respiratory musculature is
also frequently involved in patients with MG. The combination of poor respiratory
effort and an ineffective swallow with the absence of protective mechanisms can
lead to aspiration and, potentially, pulmonary infection. Indeed, Higo et al. ( 2005 )
studied the swallowing function of 11 patients diagnosed with MG via
video fl uoroscopy. Aspiration was seen in 34.8%, with half of these cases involving
silent aspiration. Three of the four cases that showed silent aspiration went on to
experience aspiration pneumonia during the follow-up term.
Unfortunately, while descriptive reports on peripheral clinical features abound,
the pathophysiological effects of MG on laryngeal muscle cell biology are currently
unknown. While it is tempting to extrapolate fi ndings from studies conducted with
other skeletal muscle systems, our own experience with the differential effects of
Duchenne’s muscular dystrophy on ILM cell biology provides a cautionary note to
blanket application of muscle features across differing functional systems. Critical
basic and functional work is needed to further advance our understanding of MG
pathophysiology in the human.