Myasthenia gravis is characterized by episodic muscle weakness, chiefly in muscles innervated by cranial nerves, and characteristically improved by cholinesterase-inhibiting drugs. It is a disorder of the neuromuscular junction resulting in a pure motor syndrome characterized by weakness and fatigue particularly of the extraocular, pharyngeal, facial, cervical, proximal limb and respiratory musculature. The disease predominates in women, most commonly presents between 20 and 40 yr of age, but may occur at any age.
Myasthenia gravis is caused by humoral and cellular immune-mediated injury of the post-synaptic neuromuscular junction acetylcholine receptors.
Risk factors include: Female; Age 20-40; Familial myasthenia gravis; D-penicillamine ingestion (which can produce SLE and other autoimmune reactions); and other autoimmune diseases.
Aminoglycoside and polypeptide antibiotics decrease both presynaptic acetylcholine release and sensitivity of the postsynaptic membrane to acetylcholine. Especially at high serum levels, these antibiotics may increase neuromuscular block in patients with latent or manifest defects in neuromuscular transmission. Long-term penicillamine treatment may cause a reversible syndrome that clinically and electrically resembles myasthenia gravis.
The toxin produced by Clostridium botulinum spores, which destroys terminal cholinergic nerve twigs, causes symptoms that may be confused with the Guillain-BarrŽ syndrome, poliomyelitis, stroke, myasthenia gravis, tick paralysis, and poisoning due to curare or belladonna alkaloids. Pets may develop botulism from eating the same contaminated food.
Organophosphate insecticides and most nerve gases block neuromuscular transmission by depolarizing postsynaptic receptors by excessive acetylcholine. Miosis, bronchorrhea, and myasthenic-like weakness occurs.
Acute thiamine deficiency (pellagra) is characterized by cutaneous, mucous membrane, CNS, and GI symptoms. The complete syndrome of advanced deficiency includes scarlet stomatitis and glossitis, diarrhea, dermatitis, and mental aberrations. In severe alcoholism, continued carbohydrate ingestion gradually exhausts thiamine stores in critical areas of the thalamus and brainstem reticular formation.
The specific test for myasthenia gravis is the acetylcholine receptor antibody. In generalized myasthenia it is 80% positive; and in ocular myasthenia it is 50% positive; with myasthenia + thymoma it is 100% positive; in congenital myasthenia it is 0% positive. There is no clear correlation between antibody titer and disease severity. Thyroid function tests should be checked.
Diagnosis is confirmed by improvement with anticholinesterase drugs: Edrophonium. Cholinergic drugs include: Pyridostigmine, Neostigmine, Atropine, Propantheline, and Ephedrine.
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