Muscle Weakness

My father was diagnosed 9 years ago with Myasthenia Gravis and had a Thymectomy.  Mestinon, Cellsept, and Imuran have not alleviated his symptoms. Currently he is on 7.5 mg of Prednisone. The muscles in his entire body (except his eyes) have gradually worsened over the years. He also suffers from two other serious diseases: polycystic kidney disease and pemphigus. It has been challenging for his doctors to treat all three of these illnesses.  For some reason, his general practitioner is not sure that his muscle weakness is due to the Myasthenia.  Is there anything else that he could try for the Myasthenia or is it possible that there is another diagnosis?  Thank you for your help, Barbara

[Joanna Fong, MD]

Hi Barbaraspr,

Myasthenia Gravis is a neuromusclar junction disease (affecting the area connecting the nerves and muscles).  I will give you a brief overview of what MG is:

"Myasthenia gravis (MG) is the most common disorder of neuromuscular transmission. It is now one of the best characterized and understood autoimmune disorders. The hallmark of the disorder is a fluctuating degree and variable combination of weakness in eye muscles, speech, swallowing, face muscles, limb, and respiratory muscles. Weakness is the result of an antibody-mediated, T-cell dependent immunological attack directed at proteins in the neuromuscular junction (acetylcholine receptors and/or receptor-associated proteins).

Myasthenia is a relatively uncommon disorder with an annual incidence of 10 to 20 new cases per million people (10 in the United States and 15 to 20 per million in Cyprus and Spain) and a prevalence of 100 to 200 per million. The prevalence of the disease has been increasing over the past five decades. This is thought to be due to better recognition of the disease, aging of the population, and the longer life span of affected patients. It occurs at any age, but there tends to be a bimodal distribution to the age of onset with an early peak in the second and third decades (female predominance) and a late peak in the sixth to eighth decade (male predominance).

The cardinal feature of myasthenia gravis (MG) is fluctuating skeletal muscle weakness, often with true muscle fatigue.  The weakness may fluctuate throughout the day, but it is most commonly worse later in the day or evening, or after exercise. Early in the disease, the symptoms may be absent upon awakening. Often as the disease progresses, the symptom-free periods are lost; symptoms are continuously present but fluctuate from mild to severe. When present, this fluctuation in symptoms is an important feature that can distinguish MG from other disorders that also may present with weakness, such as myopathy or motor neuron disease.

Presenting symptoms — Although myasthenia can produce weakness in any skeletal muscle group, there are certain presentations that are quite characteristic.

More than 50 percent of patients present with ocular (eye) symptoms of ptosis (drooping of eye lids) and/or diplopia (double vision). Of those who present with ocular manifestations, about half will develop generalized disease within two years. Many of the patients who present without ocular manifestations develop ptosis or diplopia at some point in the course.
About 15 percent of patients present with bulbar symptoms. These include dysarthria, dysphagia, and fatigable chewing.
Less than 5 percent present with proximal limb weakness alone.
Less common presentations include isolated neck weakness, isolated respiratory muscle weakness, and distal limb weakness.

Involvement of the muscles of respiration produces the most serious symptoms in MG. When the respiratory muscle weakness produces respiratory insufficiency and pending respiratory failure, this is a life-threatening situation called "myasthenic crisis." It may occur spontaneously during an active phase of the disease or may be precipitated by a variety of factors including surgery, infections, certain medications, or tapering of immunosuppression.

Clinical course - Early in the disorder, the symptoms of MG are often transient in many patients, with hours, days, or even weeks free of symptoms. New symptoms often develop weeks or months later. The maximal extent of the disease is seen in 77 percent of patients by three years of onset.

Diagnosis - The diagnostic approach to MG is focused on confirming the clinical diagnosis established by the history and examination findings.  Other reliable diagnosis methods are 1) Laboratory methods that aid in the confirmation are serologic tests for autoantibodies and 2) electrophysiological studies (repetitive nerve stimulation studies and single-fiber EMG). It should be kept in mind that the diagnostic sensitivity of these studies also varies considerably depending on whether the patient has ocular or generalized disease.

Treatment -
The four basic therapies for myasthenia gravis (MG) include symptomatic treatments (anticholinesterase agents), chronic immunotherapies (corticosteroids and other immunosuppressive drugs), rapid immunotherapies (plasma exchange and intravenous immune globulin [IVIG]), and thymectomy.

Acetylcholinesterase inhibitors are typically the first line of treatment for symptomatic MG. Pyridostigmine (Mestinon) is the most widely used choice. A typical starting dose is 30 mg three times a day. The dose of pyridostigmine is then titrated by its effect.

Most patients with MG will need some form of immunotherapy in addition to pyridostigmine. We recommend adding immunotherapy for patients who remain significantly symptomatic on pyridostigmine, or who become symptomatic after a temporary response to pyridostigmine. Corticosteroids, mycophenolate mofetil, azathioprine, and cyclosporine are the most widely used.

Plasmapheresis and IVIG work quickly but have a short duration of action. In addition to treatment of myasthenic crisis, these rapid therapies are useful in presurgical treatment of moderate to severe MG. They are also used as a "bridge" when initiating slower acting immunotherapies, and as periodic adjuvants to other immunotherapeutic medications in refractory MG.

According to the proposed guideline, thymectomy is for patients with generalized MG who are less than age 60 without thymoma. However, it generally takes years for the benefits of thymectomy to accrue. We suggest not performing thymectomy in patients 60 or older without thymoma.

A number of drugs can unmask or worsen myasthenia. Avoidance of aminoglycoside antibiotics, magnesium sulfate, penicillamine, and interferon-alpha in patients with MG is prudent. Likewise, beta blockers, procainamide, quinidine, and quinine should be avoided when possible.

Good luck.

THIS INFORMATION IS PROVIDED FOR GENERAL MEDICAL EDUCATION PURPOSE ONLY.  PLEASE CONTACT YOUR PHYSICIAN FOR DIAGNOSTIC AND TREATMENT OPTIONS OF YOUR SPECIFIC MEDICAL CONDITIONS.