Myasthenia Gravis

Epidemiology

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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

  • May be effective

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

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References

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