Clinical Geriatrics

This two-part article on neuromuscular diseases in geriatric patients focuses on the conditions that occur with regularity in older persons or have a striking effect on their lives. Part I, published in the February 2010 issue of the Journal, discussed cervical spondylotic radiculomyelopathy, lumbar spondylosis, amyotrophic lateral sclerosis, Guillain-Barré syndrome, and acquired demyelinating polyneuropathies. Part II focuses on myasthenia gravis, inclusion body myositis, polymyositis, and polymyalgia rheumatica.

Myasthenia Gravis
The hallmark of this autoimmune disease is fatigable strength that improves with rest.¹ Presentation may be: (1) primarily ocular: ptosis and extraocular movement abnormality leading to diplopia; (2) bulbar: weakness of muscles of mastication leading to fatigable chewing and prolonged meal times, dysphagia, regurgitation of liquids into the nasal passages, and nasal speech due to palatal weakness; or (3) generalized: usually symmetric proximal limb weakness, neck extensor weakness presenting as head drop or diaphragmatic weakness. In 15% of patients, the disease remains largely confined to the extraocular muscles and eyelids. The remaining 85% of patients have generalized myasthenia gravis. Occasionally, patients will present with respiratory failure (myasthenic crisis) or failure to wean from mechanical ventilation after they have been intubated for an unrelated reason. Anti-MuSK (muscle-specific kinase) seropositive patients have a higher frequency of bulbar involvement and respiratory crises.^2,3 There is no sensory involvement, and deep tendon reflexes are unaffected.

The prevalence of myasthenia gravis is between 50-125 cases per million population, and the incidence is bimodal; the first peak is in females in their second or third decade, and the second peak is in males in their sixth or seventh decade.¹

Serum anti-acetylcholine receptor (AChR) antibody testing (binding, blocking, and modulating), anti-MuSK antibody testing, nerve conduction studies (NCS) including repetitive nerve stimulation and electromyography ± single-fiber electromyogram (EMG) are the diagnostic cornerstones for this disease. AChR antibody testing has 99% specificity and 80-90% sensitivity in patients with generalized myasthenia.^4,5 In patients who are initially seronegative, it may be worth repeating the antibody testing in 12 months, as a Mayo Clinic cohort found that 15.2% of initially seronegative patients became senopositive with testing at later dates.⁵ In patients with purely ocular myasthenia gravis, seropositivity drops to approximately 60%. In AChR antibody-negative myasthenia gravis, the antibody involved is directed toward an epitope located on or near the AChR (eg, antibodies against MuSK), which are found in 20-38%^3,5 of “seronegative” patients, or against striated muscle (present in 85% of thymoma patients). Between 10-15% of patients will have a thymic neoplasm uncovered on chest computed tomography, and 65% of the remaining patients will have a thymic hyperplasia.⁴

NCS and EMG eliminate neurogenic or myopathic causes for the muscle weakness. Repetitive nerve stimulation, whereby a peripheral nerve is stimulated at a frequency of 2-3 Hz and the ensuing compound muscle action potentials (CMAPs) recorded, will show a 10% (or greater) decrement in the amplitude of the CMAP. This is characteristic of a postsynaptic disorder and is positive in over 70% of patients with myasthenia gravis; the sensitivity is increased by studying muscles that are clinically involved. Single-fiber EMG, which has greater than 90% sensitivity, is of particular value in ocular myasthenia gravis.

Other diagnostic tests include the icepack test, in which an icepack is applied over a ptotic eye for as long as the patient can tolerate (usually minutes).