Myasthenia Gravis
Jill C. Cash
Definition
A.Myasthenia gravis (MG) is a chronic autoimmune disorder that affects the neuromuscular junction and is characterized by fatigability and weakness of voluntary muscles.
Incidence
A.The prevalence is 0.5 to 11.5 cases per one million people. There are two peaks in MG incidence that are age- and gender-related: One is women in their 20s and 30s, and the other is men in their 60s and 70s.
Pathophysiology
A.MG is believed to be an antibody-mediated autoimmune attack that destroys variable numbers of acetylcholine receptors (AChR) at the postsynaptic junction. The decrease in AChRs results in weakness with repeated activities and recovery after rest. MG is often associated with thymic hyperplasia or tumors; the thymus plays an unclear role in the autoimmune process of MG.
Predisposing Factors
A.No predisposing factors have been identified.
Common Complaints
A.Classic triad: Ptosis, diplopia, and dysphagia:
1.Fluctuating symptoms such as droopy eyelid(s).
2.Blurry or double vision.
3.Sense of choking.
B.Difficulty chewing.
C.Slurring of speech.
D.Easy fatigability.
E.Symptoms are more pronounced with fatigue or in the evening.
Other Signs and Symptoms
A.Selected voluntary muscles that fatigue with activity.
B.Motor function that improves with rest but then decreases with use.
C.Signs of impending MG crisis:
1.Sudden onset of inspiratory distress.
2.Difficulty swallowing.
3.Visual difficulty.
4.Tachycardia.
5.Rapid onset of weakness.
Subjective Data
A.Establish onset of symptoms and possible progression.
B.Ask the patient what makes the symptoms better or worse: Does rest help?
C.Ask if the patient feels better in the morning or in the afternoon or evening.
D.Look for difficulties with chewing or swallowing.
E.Investigate medications the patient is currently taking or has recently taken, such as antibiotics.
Physical Examination
The presentation and course of MG are both highly variable, and MG can therefore be very difficult to diagnose.
A.Check pulse, respirations, and blood pressure (BP).
B.Inspect:
1.Observe overall appearance.
2.Perform complete eye exam. Subtleties of eye movement dysfunction are often key in differentiating MG from other disorders.
C.Palpate: Assess deep tendon reflexes (DTRs) note normal to increased reflexes.
D.Neurologic exam:
1.Perform complete neurologic exam.
2.Test the following:
a.Muscle strength: Weakness is increased with repetition or sustained activity; arm raise cannot be sustained.
b.Eyes:
i.Upward or lateral gaze cannot be maintained for longer than 30 seconds.
ii.Eyes: Ptosis occurs with repetitive lid closure.
iii.Ice pack test: Fill a plastic bag or glove with ice and place over closed eyelid for 2 minutes. Remove ice and evaluate the degree of ptosis. Noted to be very sensitive with prominent ptosis.
c.Voice: Voice quality or speech changes when counting out loud to 100.
Normal coordination, normal sensory perception, and normal pupillary response are noted in MG.
Diagnostic Tests
A.Antibody titer for acetylcholine receptor (AChR-Ab) is positive in 90% of patients with MG. May also perform MuSK antibody titer. Approximately 6% to 12% of patients will have negative antibody titers for both titers.
B.Cholinesterase-inhibiting drug test: Improvement in strength following injection of edrophonium (Tensilon).
C.Repetitive muscle stimulation test: Decremental response.
D.Single-fiber electromyographic (EMG) and/or repetitive nerve stimulation (RNS) studies are diagnostic studies performed for diagnosis.
Initial diagnostic tests may be equivocal with some negative test results, but this does not absolutely rule out myasthenia gravis.
Differential Diagnoses
A.MG: The most common disorder of neuromuscular transmission. It is important to maintain a high index of suspicion and include MG in the differential diagnosis of any patient presenting with variable muscle weakness even without eye signs.
B.Incomplete extraocular nerve palsy.
C.Polymyositis.
D.Brainstem transient ischemic attack (TIA).
E.Amyotrophic lateral sclerosis (ALS).
F.Brainstem vascular accident: Dizziness
is a symptom rarely seen with MG but often associated with brainstem ischemia.
G.Guillain–Barré syndrome (GBS).
H.Brainstem tumor.
I.Hyperthyroidism or hypothyroidism.
J.Cholinergic crisis: Although it is useful to distinguish myasthenic crisis (weakness from MG exacerbation) from cholinergic crisis (weakness from too much medication), both can rapidly lead to respiratory failure. Transportation to an emergency room for evaluation should not be delayed by attempts to differentiate the two.
K.Eaton-Lambert myasthenic syndrome: Often associated with bronchogenic carcinoma but may precede detection of the carcinoma by as many as 2 years.
Plan
A.General interventions:
1.MG is primarily managed by a neurologist, given the difficulty in diagnosing it, the variable course of the disease, and the highly individualized medication regimen required.
2.The course of MG fluctuates most during the first 3 to 5 years after diagnosis.
3.Autoimmune disorders, such as thyroid disease, rheumatoid arthritis, and systemic lupus erythematosus (SLE), should also be screened for in patients diagnosed with MG.
B. 
See Section III: Patient Teaching Guide Myasthenia Gravis
:
1.Patients should have a MedicAlert tag and always carry a list of their medications and dosing schedules in case of an emergency.
C.Medical and surgical management.
1.Thymectomy is an early consideration; an MRI of the chest is obtained once the diagnosis is made to assess for thymic enlargement.
Thymectomy lessens the severity of MG but rarely results in complete elimination of the need for medication.
2.Plasmapheresis, or plasma exchange to remove antibodies, is used emergently for the management of myasthenic crisis. Opinion is mixed regarding its use in the long-term management of myasthenia.
3.A myasthenic crisis occurs when the muscles that control breathing are weakened to the point of requiring ventilation. This usually is triggered by an infection, fever, or adverse reaction to a medication.
D.Pharmaceutical therapy:
1.Many medications can worsen myasthenic symptoms, so changes and additions of any medication require consultation with the patient’s neurologist. Cholinesterase-inhibiting medications:
a.Pyridostigmine (Mestinon) 60 mg and 180 mg sustained release (SR) titrate as needed, with usual dose up to 600 mg/d.
b.Neostigmine methylsulfate (Prostigmin) 0.25 to 0.5 and 1.0 mg/mL concentrations titrated with starting dose 0.5 mg SC or intramuscular (IM) every 3 to 4 hours.
2.Steroids may be used when inpatient and then tapered on an outpatient basis, tapering every 3 days.
3.Effectiveness of medication regimen is gauged by changes in ptosis, diplopia, dysphagia, chewing ability, and muscle fatigue.
4.Care should be used with use of medications that may worsen symptoms of weakness.
Follow-Up
A.Patients with MG require lifelong management by a neurologist, given the variable course of both the disease and the patient’s response to treatment.
B.The patient is initially followed every 1 to 2 months, then every 3 to 4 months.
Consultation/Referral
A.If MG is suspected, consult with a physician and consider neurologic referral.
Individual Considerations
A.Pregnancy:
1.MG is considered high risk for both the woman and the fetus:
a.Pregnancy requires management by the patient’s neurologist and a perinatologist.
2.MG frequently manifests for the first time during pregnancy. Refer to a perinatologist.
B.Adults:
1.Oral contraceptives may worsen myasthenic symptoms.