Myasthenia Gravis: Causes

Pathogenesis (disease development)

Myasthenia gravis is one of the autoimmune diseases. In this case, antibodies are directed against the body’s own structures, in this case against structures of the postsynaptic (located behind the junction (synapse)) membrane in the area of the motor end plate of the striated (voluntarily movable) muscles (skeletal muscles). In about 85% of cases, the antibodies are directed against the nicotinic acetylcholine receptor (AChR). As a result, the interaction between the transmitter acteylcholine and the acetylcholine receptor is impaired (→ muscle weakness) or blocked (→ muscle paralysis). The electrical impulse cannot be transmitted from the nerve to the muscle. In addition, the number of postsynaptic acetylcholine receptors is reduced. Antibodies to muscle-specific tyrosine kinase (MuSK) and very rarely to low-affinity acetylcholine receptor antibodies or antibodies to lipoprotein receptor-related protein (LRP4) can be detected in 1-10% of cases. However, there also remains a certain number of patients in whom no antibodies can be detected. It is suspected that, in addition to the antibodies mentioned above, other antibodies can lead to the clinical picture. Connections to the thymus (sweetbread/part of the immune system) as well as to the disturbed signal transmission from nerve to muscle underlying the disease have also been proven. The thymus seems to play a role in the pathogenesis of myasthenia gravis. In childhood, the antibodies are formed there. Pathologic (pathological) changes are frequently detectable in those with the disease. In about 70% of cases, there is thymitis (inflamed thymus with increased activity) with active germinal centers. In another 10-15%, a thymoma (tumor of the thymus) is detectable, with about half of these being malignant (malignant). Surgical removal can positively influence the course of the disease.

Etiology (causes)

The causes of myasthenia gravis are as yet unclear. Biographic causes

• Genetic burden – disease risk of 4.5% for siblings of individuals suffering from neuromuscular disease.

Existing myasthenia gravis may be worsened by the following factors:

• Inflammation
• Fever
• Heat
• Hormonal fluctuations – during menstruation.
• Infections
• Physical stresses
• Medications (A claim to completeness does not exist!)
  • Analgesics
    • Flupirtine
    • Morphine preparations
  • Antiarrhythmic drugs – quinidine, ajmaline, mexitil, procainamide.
  • Antibiotics
    • Aminoglycosides – v. a. Streptomycin, Neomycin, less Tobramycin.
    • Macrolides – e.g., erythromycin
    • Ketolides – telithromycin/Ketek
    • Lincomycins
    • Polymyxins
    • Gyrase inhibitors – levofloxacin, ciprofloxacin, prulifloxacin.
    • Sulfonamides
    • Tetracyclines
    • Penicillins – only in particularly high dosage.
  • Antidepressants – amitriptyline-type substances.
  • Anticonvulsants – benzodiazepines, carbamazepine, diphenylhydantoin, ethosuximide, gabapentin.
  • Antimalarials – quinine, chloroquine and analogs.
  • Antirheumatic drugs – chloroquine, etanercept
  • Beta-blockers – oxprenolol, pindolol, practolol, propranolol, timolol – also used topically as eye drops.
  • Botulinum toxin
  • Calcium antagonists – verapamil, diltiazem, nifedipine and relatives.
  • Diuretics – acetazolamide, benzothiadiazines, loop diuretics.
  • Glucocorticoids (clinically relevant worsening is rare at intermediate doses or insipid dosing)
  • Interferons – interferon-alpha (isolated cases).
  • Lithium
  • Local anesthetics – procaine (ester type), the amide type substances used today are not problematic.
  • Magnesium – high doses as laxatives (laxatives).
  • Monoclonal antibodies: durvalumab (rare).
  • Muscle relaxants
    • Curare derivatives – due to increased sensitivity, initially (starting) choose 10-50% of normal dosage
    • Succhinylcholine – Should generally not be used because it cannot be antagonized with pyridostigmine!
  • Narcotics
  • Psychotropic drugs – chlorpromazine, promazine and relatives, all benzodiazepines and structural relatives such as zolpidem, zopiclone
  • Statins – multiple reports of findings on various cholesterol-lowering drugs.
• Thyroid disease
• Mental stress
• Vibrations