Page 910 - Clinical Immunology_ Principles and Practice ( PDFDrive )

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Myasthenia Gravis

Arnold I. Levinson

Myasthenia gravis (MG) is a disease characterized by weakness but typically the palatal, pharyngeal, and upper esophageal muscles
of striated muscles. The weakness is caused by impaired neuro- are involved. This results in dysarthria, dysphagia, and difficulty
muscular transmission resulting from a reduction in the number handling secretions. Involvement of the diaphragm and intercostal
of receptors for the neurotransmitter acetylcholine (ACh) at the muscles produces dyspnea and may lead to respiratory failure.
postsynaptic myoneural junction. In most cases, this reduction Involvement of the muscles of the extremities and trunk occurs
is the result of the action of anti–acetylcholine receptor (anti- in 20–30% of patients at initial presentation and causes difficulties
AChR) antibodies. The disease occurs with a reported prevalence with activities of daily living. The hallmark of all muscle involve-
of 0.5–5/100 000 and an incidence of 0.4/100 000/year. Although ment in MG is its variability over time, with weakness usually
MG can occur at any age, it typically presents in the second and exacerbated by repetitive use.
third decades of life, with a later peak occurring after age 50 Furthermore, within the group of patients with generalized
years (late-onset disease). A female preponderance (3:1–4:1) has disease, patients are further subdivided into subtypes on the
been reported in the first 40 years of life; thereafter, the incidence basis of age of onset, for example, early-onset MG (EOMG) and
is comparable between the sexes. late-onset MG (LOMG) with onset before and after age 50 years,
respectively. Moreover, patients can be additionally distinguished
CLASSIFICATION by their profiles of serum autoantibodies (see discussion of serum
autoantibodies) and the presence/absence of thymic pathology
Patients with MG have traditionally been divided into two (see discussion of thymic pathology).
categories: those with generalized disease and those presenting
1
with disease limited to the ocular muscles. Within these two CLINICAL PEARLS
groups, patients can be further subdivided on the basis of age Telltale Signs of Myasthenia Gravis
of onset. Neonatal MG affects 10–20% of offspring born to
mothers with myasthenia. Disease manifestations are those of • Variable muscle weakness
generalized MG (see below) but are transient, dissipating with • Weakness in cranial nerve distribution
the metabolism of maternal anti-AChR antibodies that had been • Normal reflexes and sensation
transmitted across the placenta during the third trimester of
pregnancy. Several congenital myasthenic syndromes have been DIAGNOSIS
described. For the most part, these manifest during the neonatal
period, persist into adulthood, and are not considered to have The differential diagnosis is extremely broad, encompassing
2
an autoimmune basis. Juvenile MG is said to occur in those neuropathies, primary and secondary myopathies, muscular
patients who present with disease between 1 year of age and dystrophy, demyelinating disorders, degenerative diseases,
puberty. Apart from the age of onset, juvenile myasthenia behaves cerebrovascular accidents, mass lesions, and infectious diseases.
like adult MG. The clinical features that point to a diagnosis of MG include
Adult patients may present with ocular involvement or signs the variable nature of the muscle weakness, normal sensation,
of more generalized disease. The ocular involvement is character- and normal deep tendon reflexes. The diagnosis can usually be
ized by impaired ocular muscle motility and lid weakness, confirmed by pharmacological and electrophysiological testing.
manifesting as diplopia and ptosis, respectively. The vast majority A decremental pattern is characteristically seen following repetitive
of patients with MG will experience ocular involvement, with nerve stimulation (Fig. 65.1), and this pattern is normalized
roughly 50% of patients presenting with ocular signs at the time following treatment with the anticholinesterase agent tensilon.
of diagnosis. Those generally at risk of disease progression are Further confirmation rests on detecting anti-AChR antibodies,
(i) patients with evidence of subclinical disease on electrophysi- which are found in 85–90% of patients with generalized disease.
ological testing of limb muscles; and (ii) patients who have In the standard assay, sera are reacted with a nicotinic AChR
markedly elevated titers of anti-AChR antibodies. Typically, preparation labeled with 125 I-α-bungarotoxin, a snake venom
patients with ocular symptoms for >2 years will not progress to polypeptide that binds irreversibly to the receptor. Bound antibod-
a more generalized form of disease. ies are immunoprecipitated by an antiimmunoglobulin reagent
In the generalized disease group, patients can be classified or staphylococcal protein A, and the quantity of antibodies
into those with mild, moderate, or severe disease on the basis detected is expressed in terms of the amount of α-bungarotoxin
of clinical activity. Any skeletal muscle group can be affected, bound.

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