MOTOR ENDPLATE DISORDERS flattened, which results in decreased efficiency

Myasthenia Gravis of neuromuscular transmission. The

Overview and Definition neuromuscular junction can normally transmit
Myasthenia gravis (MG) is the most at high frequencies so that the muscle does not
common of the disorders of neuromuscular fatigue. Without ACh, the nerve impulses fail to
transmission. It is characterized by fluctuating pass across the neuromuscular junction to
weakness and fatigability of skeletal muscles. stimulate muscle contraction. The
neuromuscular abnormalities in MG are brought
Incidence about by an autoimmune response mediated by
The incidence of MG is estimated at specific anti-ACh receptor antibodies. The
1:200,000. Estimates from the National antibodies may block the site that normally
Myasthenia Gravis Foundation are that there are binds ACh, or the antibodies may damage the
over 100,000 clients with MG and an additional postsynaptic muscle membrane. There may be
25,000 undiagnosed cases. MG can affect people endocytosis (pinching off of regions of the cell's
in any age group, but peak incidences occur in membrane) of the receptor site.
women in their twenties and thirties and in men Although the cause of the autoimmune
in their fifties and sixties. Overall, the ratio of response in MG is not well understood, the
women affected compared to men is 3:2. thymus appears to play a role in the disease; 7 5
% of persons with MG have abnormalities of the
Etiology thymus (e.g., thymic hyperplasia or thymoma).
MG is an autoimmune disorder whose Cells within the thymus bear ACh receptors on
action takes place at the site of the their surface, and may serve as a source of
neuromuscular junction and motor endplate. autoantigen to trigger the autoimmune reaction
within the thymus gland when an immunologic
Risk Factors abnormality causes a breakdown an
Disorders associated with an increased autoimmune attack on acetylcholine (ACh)
incidence of MG are thymic disorders such as receptors.3 3
hyperthyroidism, thymic tumor, or
thyrotoxicosis. There is an association with Clinical Manifestations
diabetes and immune disorders such as Although MG encompasses a spectrum
rheumatoid arthritis or lupus. Exacerbations of mild to severe, its cardinal features are
may occur before the menstrual period or skeletal muscle weakness and fatigability.
shortly after pregnancy. Chronic infections of Repetition of activity causes fatigue, whereas
any kind can exacerbate MG. Five to seven rest restores activity. Other than weakness,
percent appear to have a familial association. neurologic findings are normal. A system of four
major categories is used to classify MG: ocular,
Pathogenesis mild generalized, acute fulminating, or late
In MG, the fundamental defect is at the severe.
neuromuscular junction. Receptors at the motor The distribution of muscle weakness has
endplate normally receive acetylcholine (ACh) a dichotomous pattern affecting only the ocular
from the motor nerve terminal. An action muscles, or a more variable, generalized pattern
potential occurs that leads to a muscle occurs. In approximately 8 5 % of persons with
contraction. In MG the number of ACh receptors MG, the weakness i s generalized and affects the
are decreased and those that remain are
limb musculature. This fluctuating weakness is severity of the disease. However, in a person
often more noticeable in proximal muscles. with MG a treatment-induced fall in the
Cranial muscles, particularly the eyelids antibody level often correlates with clinical
and the muscles controlling eye movements, are improvement.
the first to show weakness. Diplopia (double The drug edrophonium (Tensilon) is used
vision) and ptosis (drooping eyelids) are to demonstrate improvement in the myasthenic
common early signs causing the person to tilt muscles by inhibiting acetylcholinesterase
the head back to see (Fig. 3 9 - 1 8 ) . Weak neck (AChE), an enzyme required for ACh uptake.
muscles may cause head bobbing in this Muscle strength and endurance are measured
position. before and after administration of the drug. This
Chewing of meat produces fatigue, and test confirms that ACh uptake is part of the
the facial expression is one that seems to be pathologic status; however, a control test of
snarling because the lips do not close. Speech saline should also be used for comparison.
tends to be nasal. Difficulty in swallowing may Electrophysiologic testing of myasthenic
occur as a result of palatal, pharyngeal, and disorders demonstrates a normal EMG at rest.
tongue weakness. Nasal regurgitation or Specialized testing must be employed using
aspiration of food is common. repetitive stimulation to demonstrate a rapid
decrement in the motor action potential's
MEDICAL MANAGEMENT amplitude. Absence of sensory deficits and
DIAGNOSIS. History and clinical observation of retention of tendon reflexes throughout the
symptoms of weakness with continued use and course of the disease also tend to confirm the
improvement with rest are important in diagnosis of MG. Because respiratory
diagnosing MG. Several conditions that cause impairment is a serious complication of MG,
weakness of cranial, or somatic, muscles must measurements of ventilatory function should be
also be considered. These include drug-induced performed.1 58
myasthenia, hyperthyroidism, botulism,
intracranial mass lesions, and progressive TREATMENT. AChE inhibitor medication
disorders of the eye. Lambert-Eaton syndrome is provides for improvement of weakness but does
a presynaptic disorder of the neuromuscular not treat the underlying disease. Administration
junction that can cause symptoms similar to of this medication is tailored to the individual's
those of MG. Lambert-Eaton syndrome is an requirements throughout the day. For example,
autoimmune disorder associated with neoplasm, a person with difficulty chewing and swallowing
most commonly small cell (oat cell) carcinoma of would take the medication before meals. Side
the lung, which is believed to trigger the effects of AChE inhibitors include
autoimmune response. gastrointestinal effects such as nausea and
The three methods used to diagnose MG vomiting, abdominal cramping, and increased
are (1) immunologic, (2) pharmacologic, and (3) bronchial and oral secretions.
electrophysiologic testing.1 0 5 Immunologic Surgical removal of the thymus is
testing detects anti-ACh receptor antibodies in successful in 8 5 % of persons with MG. Up to 3
the serum. The presence of anti-ACh receptor 5 % of those undergoing thymectomy achieve a
antibodies is virtually diagnostic of MG, but a drug-free remission, although this may take
negative test does not exclude diagnosis of the years.
disease. There is no correlation between the Immunosuppression using drugs, such as
amount of anti-ACh receptor antibodies and the corticosteroids (prednisone) and azathioprine,
are effective in nearly all persons with MG. 4C: Impaired Muscle Performance
Initially, high daily doses are begun and then Physical and occupational therapy may
followed by alternate-day high doses that are be indicated as supportive care to assist the
tapered slowly over a period of months. client with MG. In the acute care setting, the
Unfortunately, adverse side effects are therapist must establish an accurate neurologic
associated with high-dose steroids. These and respiratory baseline. Tidal volume, vital
include cushingoid appearance, weight gains, capacity, and inspiratory force should be
hypertension, and osteoporosis (see Chapter 7 ). monitored regularly during treatment. Deep
Plasmapheresis is performed to remove breathing and coughing should be encouraged.
substances that affect ACh receptors. However, When eating, the person should be instructed to
plasmapheresis produces only short-term sit upright and to swallow when the chin is
reduction in anti-AChE antibodies and is not tipped slightly downward toward the chest and
effective for long-term symptom control. never with the neck extended because of the
risk of aspiration. Finally, the client should never
PROGNOSIS. The course of MG is variable, speak with food in the mouth.
typified by remissions and exacerbations, The therapist must also be alert to signs
especially within the first year after onset. of an impending myasthenic crisis (increasing
Symptoms often fluctuate in intensity during the muscle weakness; respiratory distress; or
day. This daily variability is superimposed on difficulty while talking, chewing, or swallowing).
longer-term spontaneous relapses that may last Make sure the client recognizes the side effects
for weeks. Remissions are rarely complete or and signs of toxicity of AChE inhibitor
permanent. This disorder follows a slowly medications. For those receiving a prolonged
progressive course. Onset of other systemic course of corticosteroids, report adverse side
disorders and infections may precipitate an effects to the physician.
exacerbation of the disease and are the most Plan therapy and teach the client to plan
common cause of a crisis. A myasthenic crisis is activities to coincide with periods of maximum
a medical emergency requiring attention to life- energy (see Box 9-8 for energy conservation
endangering weakening of the respiratory tips). The home should be arranged to help
muscles. A myasthenic crisis requires ventilator prevent unnecessary energy expenditure.
assistance. Treatment of a crisis occurs in the Frequent rest periods help conserve energy and
ICU because the client requires careful, give muscles a chance to regain strength. The
immediate control of medications for survival.1 person with MG should avoid strenuous
78 exercise, stress, and excessive exposure to the
When MG begins in children, it is sun or cold weather. All of these can exacerbate
important to establish the form it takes. Because signs and symptoms.
AChE antibodies cross the placenta, 1 0% of Researchers report that a strength
newborns of mothers with MG develop a training program eliciting maximal isometric
myasthenic reaction. Newborns with neonatal contractions could be instituted in clients with
MG have a weak suck and cry and are hypotonic. mild-to-moderate MG. As long as participants
Fortunately, this resolves in a few weeks. were monitored for fatigue during periods of
exercise, improvements were noted in all
SPECIAL IMPLICATIONS FOR THE PT 39-10 muscles.9 3 After 3 months, participants' knee
Myasthenia Gravis extensor muscles showed the most significant
PREFERRED PRACTICE PATTERNS strength gains without adverse reactions.
Recently, a cooling vest was worn to decrease
core body temperature to determine whether
pulmonary function and subjective perceptions
of strength and fatigue would improve. All
measures were improved in the majority of
participants.1 0 7
Because individuals diagnosed as having
MG are placed on long-term corticosteroid
medication, the treatment may induce a
secondary condition: osteoporosis. These
individuals should be encouraged to undergo
dual energy x-ray absorptiometry (previously
DEXA, now DXA) scan and to receive calcium
supplements to counteract osteoporosis.91
The Myasthenia Gravis Foundation ( 800-
541-5454 ) publishes educational materials that
can be helpful to the client and family.

pp 1631-1633, Pathology implications for the PT,

Goodman C.C. & Fuller K.S.