MYASTHENIA GRAVIS

WHAT IS MYASTHENIA GRAVIS?

Myasthenia Gravis (MG) is a disease caused by problems with communication between the nerves and the muscles that they supply.  This communication occurs at the "synapse", the tiny gap between the end of the nerve and the muscle fibre that it supplies.  When nerve impulses traveling down the nerve towards the muscle reach the end, the nerve releases a chemical, acetylcholine (ACh) into the gap which contacts specific "receptor" (AChR) areas on the muscle surface, triggering its contraction.  In MG the immune system of the person affected produces antibodies that act against the receptors.  With fewer receptors, the affect of the ACh is reduced.  There is less muscle contraction and weakness results.  The resulting weakness tends to worsen as the muscle is used repeatedly and as normal ACh is depleted causing fatigability. 

The pattern of muscles affected vary and can include all of the muscles of the limbs, the muscles of swallowing and the muscles supplying eye movement and eyelid opening.  Sometimes one group of muscles is affected much more dramatically than the rest, especially the muscles of the eye.  This can result in eye lid drooping and double vision.  If the weakness preferentially affects the larger muscles then generalized weakness and fatigability, and sometimes shortness of breath can result.

CAN OTHER PROBLEMS LOOK LIKE MG?    

Yes.  Depending on the pattern of weakness, MG can sometimes look like several other diseases affecting muscles (myopathies), peripheral motor nerves (peripheral neuropathy) or even some types of stroke that affect eye movement.  There are also other immune diseases that affect the neuromuscular junction in different ways (e.g. Lambert-Eaton Syndrome).  The marked fatiguability of individual muscles with repeated use is usually the most telling feature of MG. In addition, the diagnosis can usually be confirmed by electromyography testing, tensilon testing as well as measurement of the abnormal antibody (anti acetylcholine receptor antibodies) in the blood. 

WHAT CAN I DO ABOUT IT?

MG is a potentially serious disease which can cause disabling weakness and even death depending upon its severity.  At other times it can be relatively mild, and in about 5% of patients may go into remission spontaneously. 

Fortunately there are several treatments options available.  The standard of therapy is with a group of drugs called anti acetylcholine esterase inhibitors (i.e.; pyridostigmine).  These drugs block the breakdown of acetylcholine in the synapse, allowing it to act for a more prolonged period on any remaining receptors on the muscle, compensating for the reduced number of receptors and improving strength.  Use of these medications can be limited due to side effects including abdominal cramps, diarrhea, sweating, nausea and slow heart rate.

In addition to boosting the affect of the acetylcholine to improve strength, several other therapies are aimed at suppressing the abnormal immune system response that is leading to the disease in the first place.  This can be done surgically by removing the thymus gland in the chest.  This option is often employed with patient's who have generalized MG below the age of 65. 

Several drugs can also alter the immune response and improve disease.  These include corticosteroids, azothioprine and cyclophosphamide. 

Short term treatment for episodes of acute weakness not responding to medication can sometimes include plasma exchange and intravenous immune globulin.

Some drugs may make the symptoms of MG worse. These agents reduce the safety margin of neuromuscular transmission and should be avoided or used with great caution. They include aminoglycoside antibiotics (eg, streptomycin, polymyxin, colistin, kanamycin, gentamicin), quinine, quinidine, and procainamide.

Ampicillin, erythromycin, chlorpromazine, morphine and beta-adrenergic blockers can also worsen defects of neuromuscular transmission and should be used with caution. The contrast agent for magnetic resonance imaging, gadolinium diethyline-triamine-pentaacetic acid can also worsen myasthenia gravis.

Dr. R. O'Brien

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