Download Myasthenia Gravis (Judy Liu MD/PhD)

Myasthenia Gravis (Judy Liu MD/PhD)
Clinical Presentation:
Myasthenia gravis is an immune-mediated disease of the neuromuscular junction.
Patients usually present with weakness and fatigability of ocular, bulbar, and/or proximal
muscles. Onset of symptoms may be quite indolent and myasthenia is often associated
with other autoimmune conditions.
--Ptosis and diplopia occur early in disease in about 40% of patients and but eventually
almost all patients have ocular weakness complaining of fluctuating diplopia and droopy
eyelids. This may be elicited by having the patient hold an upgaze for 1 minute without
closing the eyes causing an exacerbation of diplopia and ptosis. The pupil is spared in
myasthenia.
--Facial and oropharyngeal muscle weakness can cause dysarthria, dysphagia and the
characteristic transverse smile. Patients tend to have a nasal speech. Swallowing may be
affected with choking episodes or food and fluid may come out of the nose due to
weakness in the oropharyngeal muscles.
--Proximal weakness may also be present including neck flexors and extensors. Patients
will have difficulty arising from a chair, going up or down stairs, or combing their hair.
Repetitive testing of a proximal muscle group will lead to pronounced weakness.
Myasthenic Crisis: In a patient with myasthenia, acute worsening can result in
respiratory compromise. Patients with myasthenia may become weak in the setting of
infection, electrolyte abnormality, use of a new medication, or change in medication to
treat myasthenia including steroids.
Cholinergic Crisis: Although cholinergic crisis is unusal, cholinergic excess can cause
weakness as well. However, a cholinergic crisis should not happen if the patient is
treated correctly with immunosuppression in addition to mestinon. Theoretically,
edrophonium (tensilon test) may be helpful in differentiating myasthenic crisis from
cholinergic crisis.
1. Medicationsa. Generally, cholinesterase inhibitors should be stopped in the setting of
crisis.
b. Medications contraindicated in myasthenia
i. Aminoglycosides, clindamycin, erythromycin, lithium,
phenytoin, polymyxin B, procainamide, beta blockers, quinine,
quinidine, tetracycline, calcium channel blockers, and
magnesium salts.
ii. Anesthetics
1. neuromuscular blocking agents should be used sparingly
2. may need greatly increased doses of depolarizing blocking
agents
3. non depolarizing agents cause pronounced and long acting
weakness
2. Consider admission to ICU especially for shortness of breath or suspicion of
aspiration.
3. Follow forced vital capacity (FVC) and negative inspiratory force (NIF).
65ml/kg –normal FVC
30ml/kg FVC associated with decreased cough.
25 ml/kg FVC sigh mechanism is impaired and hypoxemia develops.
15ml/kg FVC or NIF less than -20, elective intubation is necessary.
Initial vent setting: FIO2 100%, may titirate to PaO2 75-85, PEEP 3-5, Tidal vol
12ml/kg, Resp rate 12 per minute, Insp flow rate of 30-40 L/min.
4. Check for signs of infection CXR/ UA/blood cultures etc...
5. Plasma exchange 5-6 times in 2 weeks or IVIG.
Edrophonium (Tensilon) Test: It is most useful when there is a particularly weak
muscle to assess. It should be done double blinded. The patient should be on a cardiac
monitor and a vial of atropine should be on hand in the event of heart block. One
syringe should contain 10mg of tensilon and the other saline. Have a saline flush on hand
for both injections. One syringe is selected and 2mg test dose is given followed by a
saline flush. After one minute the remaining 8mg is given. Response to tensilon should
be seen within 3 minutes. These steps are repeated with the remaining syringe. In
myasthenia, the tensilon test will be dramatically positive-especially in patients with
ocular symptoms. However, there is a very high false positive rate. Many
neuromuscular disorders can have some improvement, although not as dramatic. Use
extreme caution in the elderly patient with heart disease.
Treatment:
Cholinesterase inhibitors:
Pyridostigmine bromide (Mestinon) 30mg q 6 hours gradually titrating to higher dose up
to or q 4 hours. Available also as extended release, Mestinon Timespan 180mg qhs.
Side effects include nausea, vomiting, abdominal cramps, diarrhea and increased
secretions.
Bromide intoxication is rare but can present as acute psychosis.
Immune modulation: Mainly to achieve better long term control. Steroids are the usual
first line agent and should be started in hospital as they may acutely worsen weakness.
Starting dose of prednisone is 1mg/kg/day. After remission is achieved the steroid dose
can be gradually tapered as an outpatient over up to 6 months. Other types of immune
suppression may be more desirable. Azathioprine may be started in conjunction with the
steroid (the effects of azathioprine may take 2-3 months). Starting dose is 50mg qd
increasing to 2-3 mg/kg/day. CBC must be monitored closely and the AZA dose
decreased if the WBC count falls to 3,500-4,000. Another agent that may have a quicker
onset of action is cellcept at 500-1000 mg BID (check same labs as azathioprine).
Plasma exchange: Used in patients with severe initial presentation, myasthenic crisis,
prior to thymectomy or other surgery.
IVIG: The usual dose is 400mg/kg/day for 5 days.
Thymectomy: Especially helpful in young patients- 95% may experience improvement or
remission.
Initial Laboratory Testing: Acetylcholine receptor antibody (will be positive in 7580% of generalized MG, 50% with ocular symptoms alone), ANA, Thyroid studies, CPK,
routine EMG (which will show the decremental response to repetitive nerve stimulation),
single fiber EMG (which will show increased jitter and blocking), chest CT (to evaluate
for thymoma,mass).