Explain
the treatment alternatives for MG.
Historically, the similarity of symptoms
between MG and curare poisoning led Jolly to propose in 1895 that
physostig-mine, a cholinesterase inhibitor that was known to antago-nize
curare, would be of therapeutic value in myasthenics. In 1934, this was first
attempted by Walker and has since been the mainstay of therapy in MG.
Anticholinesterase therapy is aimed at increasing the amount of acetylcholine
available to the reduced number of active receptors, thus increasing the
likelihood of agonist–receptor interaction and therefore neuromuscular
transmission. Neostigmine, edrophonium, pyridostigmine, and ambenonium are all
effective acetylcholinesterase inhibitors. Physostigmine crosses the
blood–brain barrier, producing central nervous system symptoms, and is not used
in myasthenics for this reason. Pyridostigmine is the most common
acetyl-cholinesterase inhibitor employed because it has the fewest muscarinic
side-effects and a 3–6 hour duration of action. Pyridostigmine is administered
either intravenously 2 mg or orally 60 mg. A sustained-release preparation is
available that is active over several hours. This sustained-release
prepara-tion is often used at night to ensure strength on awakening in the
morning. Dose requirements vary from day to day. Patients usually learn to
adjust doses appropriately.
Other medical treatments of MG are directed at
decreasing the production of antibodies. Corticosteroids have been used for
many years. Controlled studies reveal that corticosteroids promote clinical
improvement in up to 80% of patients; however, prolonged therapy leads to a
high incidence of unacceptable side-effects (cataracts, osteoporosis,
hypertension, and peptic ulcers). Initiation of steroid therapy is often
associated with an exacerbation of weakness that is due to a direct inhibitory
effect on neuro-muscular transmission. Diminished antibody production and its
consequent beneficial effects are delayed. Other immunosuppressive agents have
also been used, such as azathioprine and cyclosporine.
Plasmapheresis has been used to remove
circulating antibodies and temporarily improve clinical symptoms in 45% of
patients. Several treatments are required, and improvement may last only 4 days
or as long as 12 weeks. It should be noted that plasmapheresis also decreases
pseudocholinesterase levels, which results in a prolonged duration of action of
succinylcholine.
Thymectomy has provided significant long-term
improvement in most patients. It probably decreases production, or the stimulus
for production, of antibodies directed at the nicotinic acetylcholine receptor.
Because the thymus contains myoid cells with nicotinic receptors and a number
of myasthenics have thymic abnormalities, the thymus may be responsible for the
initial pathogenesis. It may also be the source of autoreactive helper T-cells.
Thymectomy is the preferred treatment in patients under 55 years of age;
however, there is no age limit for this surgery if the patient is otherwise
medically stable.
Controversy exists as to the benefits of
different surgical approaches to the thymus. The transcervical approach
interferes less with respiratory mechanics compared with transsternal
approaches. Sternal incision may offer a greater likelihood of complete
thymectomy. Incomplete thymec-tomy results in suboptimal clinical improvement.
Advocates of the transcervical approach feel that complete thymectomy is
possible with this incision. Improvement after thymec-tomy may take months.
When thymoma is present, removal of the thymus gland via sternotomy is
required.
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