Epidemiology
Etiology
Drugs with Clear Effect on Myasthenia Gravis
Antibiotics
- Colistin (Polymyxin E, Colistimethate Sodium) (see Colistin, [[Colistin]])
- Gentamicin (see Gentamicin, [[Gentamicin]])
- Kanamycin (see Kanamycin, [[Kanamycin]])
- Neomycin (see Neomycin, [[Neomycin]])
- Streptomycin (see Streptomycin, [[Streptomycin]])
- Telithromycin (see Telithromycin, [[Telithromycin]]): exacerbation occurs within 2 hrs of administration
Neuromuscular Junction Blockers
Other
- Beta Blockers (see β-Adrenergic Receptor Antagonists, [[β-Adrenergic Receptor Antagonists]]) (Only Selected Agents Shown)
- Atenolol (Tenormin) (see Atenolol, [[Atenolol]])
- Bisoprolol (Concor, Zebeta) (see Bisoprolol, [[Bisoprolol]])
- Carvedilol (Coreg) (see Carvedilol, [[Carvedilol]])
- Esmolol (Brevibloc) (see Esmolol, [[Esmolol]])
- Labetalol (Normodyne, Trandate) (see Labetalol, [[Labetalol]])
- Metoprolol (Lopressor) (see Metoprolol, [[Metoprolol]])
- Nadolol (Corgard, Anabet, Solgol, Corzide, Alti-Nadolol, Apo-Nadol, Novo-Nadolol) (see Nadolol, [[Nadolol]])
- Nebivolol (Bystolic) (see Nebivolol, [[Nebivolol]])
- Pindolol (Visken, Betapindol, Blockin L, Blocklin L, Calvisken, Cardilate, Decreten, Durapindol, Glauco-Visken, Pectobloc, Pinbetol, Prindolol, Pynastin)
- Propafenone (Rhythmol) (see Propafenone, [[Propafenone]])
- Propanolol (Inderal) (see Propanolol, [[Propanolol]])
- Sotalol (Betapace, Betapace AF, Sotalex, Sotacor) (see Sotalol, [[Sotalol]]): with additional Class III antiarrhythmic properties (inhibits potassium channels)
- Chloroquine (see Chloroquine, [[Chloroquine]])
- Magnesium (see Magnesium, [[Magnesium]])
- Penicillamine (see Penicillamine, [[Penicillamine]]) [Ocular myasthenia gravis after D-penicillamine administration . Br J Ophthalmol. 1989 December; 73(12): 1015–1018]
- Phenytoin (Dilantin) (see Phenytoin, [[Phenytoin]]) [A case of myasthenia gravis associated with long-term phenytoin therapy. Rinsho Shinkeigaku. 1996 Nov;36(11):1262-4]
- Prednisone (see Prednisone, [[Prednisone]]): may occur with high dose, with onset days after administration
- Procaine (see Procaine, [[Procaine]])
- Procainamide (Pronestyl) (see Procainamide, [[Procainamide]])
- Quinidine (see Quinidine, [[Quinidine]])
- HMG-CoA Reductase Inhibitors (Statins) (see HMG-CoA Reductase Inhibitors, [[HMG-CoA Reductase Inhibitors]]) (Only Selected Agents Shown)
- Atorvastatin (Lipitor) (see Atorvastatin, [[Atorvastatin]])
- Fluvastatin (Lescol) (see Fluvastatin, [[Fluvastatin]])
- Lovastatin (Mevacor, Altocor) (see Lovastatin, [[Lovastatin]])
- Pravastatin (Pravachol) (see Pravastatin, [[Pravastatin]])
- Rosuvastatin (Crestor) (see Rosuvastatin, [[Rosuvastatin]])
- Simvastatin (Zocor) (see Simvastatin, [[Simvastatin]])
Drugs with Anecdotal Reports of Myasthenia Gravis Exacerbation
Antibiotics
Other
- Bretylium (see Bretylium, [[Bretylium]])
- D,L-Carnitine
- Chlorpromazine (see Chlorpromazine, [[Chlorpromazine]])
- Citrate (see Citrate, [[Citrate]])
- Emetine
- Gabapentin (Neurontin) (see Gabapentin, [[Gabapentin]])
- Lactate
- Lithium (see Lithium, [[Lithium]])
- Methoxyflurane (see Methoxyflurane, [[Methoxyflurane]])
- Radiographic Contrast (see Radiographic Contrast, [[Radiographic Contrast]])
- Trasylol
- Trihexyphenidyl
- Trimethadione
- Trimethaphan
- Verapamil (Isoptin, Verelan, Verelan PM, Calan, Bosoptin, Covera-HS) (see Verapamil, [[Verapamil]])
Physiology
- IgG Auto-Antibody Against the Motor Endplate Acetylcholine Receptor: leads to impaired neuromuscular transmission
- Effects on Respiratory Muscles: Acute/Chronic Hypoventilation
Diagnosis
- FVC: danger level <15 cc/kg
- PFT: restrictive
- Decreased VC (due to muscle weakness, decreased lung compliance, and decreased chest wall compliance)
- Good test to monitor progression of disease during myasthenic crisis
- Decreased TLC
- Increased RV (due to inability to overcome recoil of chest wall outward at volumes below FRC)
- Decreased MVV: MVV maneuvers are hazardous in MG, since repeated muscular efforts may precipitate respiratory fatigue and failure
- CXR/Chest CT Pattern
- Anti-Ach Receptor Ab: positive in 90% of MG cases
- Blocking antibodies
- Binding antibodies
- Modulating antibodies
- Tensilon Test: usually leads to marked improvement in symptoms (unlike in LEMS, where Tensilon results are less definitive)
- Repetitive Nerve Stimulation: results in decreased compound muscle action potentials (in contrast to LEMS, where it leads to increased action potentials)
Clinical
- Muscle weakness (exacerbated by muscle contraction) of ocular, bulbar, respiratory (usually, expiratory > inspiratory muscles/occasionally, respiratory involvement can be the only involved), and skeletal muscles
- Acute/Chronic Hypoventilation (see [[Acute Hypoventilation]] and [[Chronic Hypoventilation]]): acute ventilatory failure may be the initial presentation of myasthenia gravis
- MG tends to have more ocular/bulbar dysfunction than LEMS
- Symptoms tend to worsen throughout the day (in contrast to LEMS, which improves throughout the day)
Myasthenic Crisis
- Crisis due to disease progression (usually involves respiratory failure or aspiration, due to pharyngeal muscle involvement)
- Precipitants of Myasthenic Crisis
- Thymectomy: may precipitate crisis
- Surgery: may precipitate crisis (risk factors for post-operative ventilation: bulbar involvement/ expiratory muscle weakness): days of ventilatory support required can be predicted from the equation: DAYS OF SUPPORT = (550/MEP%) – 5
- Co-Existent Hypothyroidism/Hyperthyroidism (occurs in 3-8% of MG cases): excarbate MG
- Anti-Cholinergic Agents/Aminoglycosides/Procainamide: all have NMJ-blocking properties
- Infection (of any type)
Cholinergic Crisis
- Associated with excessive use of anticholinesterase inhibitors
- Most commonly seen with intercurrent infection
- Characterized by deterioration, requiring increased doses of medications
- Only way to diagnose is by stopping medication temporarily
Complications
- Aspiration Pneumonia (see Aspiration Pneumonia, [[Aspiration Pneumonia]])
- Thymoma (see Thymoma, [[Thymoma]])
- Pulmonary HTN/Cor Pulmonale (see Pulmonary Hypertension, [[Pulmonary Hypertension]]): due to hypoxia and acidosis with resultant pulmonary vasoconstriction
Treatment
Anticholinesterases
- Pyridostigmine
- Improves respiratory muscle strength/lung volumes/inspiratory and expiratory flow rates/compliance during deflation (but not inflation pressure-volume curve)
- Pyridostigmine does not affect the pattern of breathing
- Prostigmine improves respiratory muscle strength, does not increase endurance (effect can be overcome by prolonged MVV maneuver)
Steroids
Plasmapheresis
- Effective when steroids fail
- May require 3-5 exchanges before effect (because <50% of antibody is intravascular at any time)
- Approximate 70% reduction in Ab concentration: required for remission
Avoidance of Agents Which May Exacerbate Myasthenia Gravis
- Anti-Cholinergic Agents
- Aminoglycosides
- Procainamide
Prognosis
References