Managing Myasthenia Gravis

Prior to 1958, myasthenia gravis carried a mortality of 30% despite treatment, but with current therapeutic options, mortality has been practically eliminated and most cases of myasthenia gravis are not as "grave" as the name implies. In fact, for the majority of individuals with myasthenia gravis, life expectancy is not lessened by the disorder.

  

a.    Initial Therapeutic Treatment

The first line of treatment typically involves the use of acetylcholinesterase inhibitors (of which pyridostigmine bromide is the most widely used). This drug inhibits the breakdown of acetylcholine at the neuromuscular junction thus increasing the availability of acetylcholine to stimulate the receptors and facilitate muscular activation and contraction. These drugs are for symptomatic treatment. They are helpful as an initial therapy in newly diagnosed patients, and as long term treatment of milder, especially ocular symptoms.

 b.    Immunosuppresants

The role of these drugs is to suppress the immune system, thereby reducing the autoimmune action against the neuromuscular junction. There are two groups of drugs. The first are the steroids and typically prednisolone is used. The second group of drugs are the steroid-sparing agents whch are initiated to allow patients to withdraw from long term steroid use which can cause unwanted side-effects. These include azathioprine, methotrexate, mycophenolate and cyclosporine

 c.    Thymectomy (surgical removal of the thymus gland)

We have previously mentioned how the thymus gland is thought to play a part in the development of MG. Therefore, thymectomy is considered a form of treatment of MG. For patients who have evidence of a thymic tumour (thymoma), thymectomy is essential. However, thymectomy can also be of benefit for patients who do not have an enlarged tumour on chest imaging. This is because a high proportion of patients with MG are likely to have an overactive thymus gland (hyperplasia) and so, removing this can help control symptoms in up to two-thirds of patients. At present, thymectomy should be considered in patients who have a positive acetylcholine receptor antibody status with a generalized form of MG and medically fit for surgery. 

 d.    Other forms of treatment

Short term therapies such as intravenous immunoglobulin or plasmapheresis are typically used in severe exacerbation of MG and also prior to thymectomy in those whose MG are not as well controlled. Both treatments are quick to show benefit but their effects are not long-standing.

 e.    Myasthenic crisis

Patients who have a severe exacerbation of MG with impending respiratory failure are considered to be in myasthenic crises. In this group of patients, not only do they require either intravenous immunoglobulins or plasma exchange but also, respiratory support on a ventilator whilst they overcome the crisis. Often, patients will also have difficulties in swallowing and so a temporary feeding tube such as a nasogastric tube will also need to be inserted. Any underlying source for the exacerbation such as infections also requires aggressive treatment.

 f.     Avoidance of exacerbating factors in MG

Other than infections, certain drugs can also cause worsening of MG to various degrees. Table 1 lists these as follows:

 

Table 1. List of pharmacological agents that might aggravate myasthenia gravis

Antibiotics

Aminoglycosides, ampicillin sodium, ciprofloxacin hydrochloride, erythromycin, imipenem, kanamycin sulfate, pyrantel, chloroquine

Cardiovascular Agents

Beta-blocking agents ( propanolol hydrochloride, oxyprenolol hydrochloride, timolol maleate), procainamide, verapamil hydrochloride, propafenone hydrochloride, quinidine

Anticholinergic Agents

Trihexyphenidyl hydrochloride, acetazolamide

Neuromuscular Blocking Agents

Vecuronium bromide, succinylcholine chloride

Ocular Drugs

Timolol maleate, proparacaine hydrochloride, tropicamide

Others

Phenothiazine antipsychotics, Penicillamine, Phenytoin sodium, Magnesium salts and lithium carbonate

  

References:

1.    Hart, I. Myasthenia Gravis - the essentials. Eurocommunica Publications 2006. 2nd Edition.

2.    Buckley C. Diagnosis and treatment of myasthenia gravis.Prescriber 2000;19

3.    Drachman DB. Myasthenia gravis. N Eng J Med 1994; 330: 1797-181

4.    Vincent A and Drachman DB. Myasthenia Gravis. (In: eds Pourmand R, Harati Y. Neuromuscular Disorders, Lippincott, Williams & Wilkins)  2001; 11: 159-188

5.    Mestinon® Prescribing Information for Physicians.

6.    Skeie G.O et al. Guidelines for the treatment of autoimmune neuromuscular transmission disorder. European Journal of Neurology 2006, 13:619-699

7.    Mcgraw-Hill. Myasthenia Gravis and other diseases of the neuromuscular junction. Harrison’s Principles of Internal Medicine, 17th edition, chapter 381