Myasthenia Gravis

Optometric Management, Jun 2006 by Gupta, Deepak

Ocular manifestations are often the first sign a patient has this rare disease.

Myasthenia gravis (MG) is a common immunological disorder of neuromuscular transmission. As primary care optometrists, many of us see patients with the ocular manifestations of this disease. Proper management includes interaction with both the patient's primary care physician and neurologist, so we must all have a working knowledge of the essentials of this condition.

Presentation

Fortunately, this condition is relatively rare, with a prevalence of 14 per 100,000 Americans. This translates to roughly 36,000 cases in the United States. The disease demonstrates no racial preference and is usually found at any age in both sexes. Patients with myasthenia gravis usually have a chief complaint centered around a specific muscle weakness vs. generalized fatigue. This muscle fatigue is generally brought on by sustained or repeated muscle activity.

The most common ocular manifestations - ptosis or diplopia - are the initial symptoms of MG in nearly two-thirds of patients. Ocular involvement can occur in isolation or in association with generalized disease. It's estimated that ocular involvement is present in up to 90% of patients at some point during the course of the disease. It is the initial presentation in 84% of cases and is the sole presentation in roughly half. The most commonly involved ocular structure is the levator palpebrae. Extraocular muscle involvement is also common, with a variety of presentations including diplopia and blurred vision.

Another 15% complain of oropharyngeal muscle weakness, difficulty chewing, swallowing, or talking as the initial symptom. Finally, limb weakness is the presenting complaint in 10%. The most common presentation of weakness fluctuates, being the least severe in the morning and worse as the day progresses, especially after prolonged use of affected muscles.

The clinical presentation of MG includes muscle fatigue after repeated or prolonged use of the muscle, with improvement seen after a period of rest. Signs and symptoms include limb and facial weakness, slurred speech and pharyngeal weakness. The severity of symptoms usually peaks between one and three years after the onset of symptoms.

The course of MG is variable but usually progressive. Maximum weakness occurs during the first year in two-thirds of patients. In the early stages of the disease, patients will often exhibit spontaneous improvement of these symptoms. During the active stage of the disease, these symptoms tend to fluctuate over a relatively short period of time and then become progressively severe for several years. The active stage is followed by an inactive state, in which fluctuations in strength still occur but are attributable to fatigue, inter-current illness, or other identifiable factors. After 15 to 20 years, patients' recovery from the weakness diminishes and the most severely involved muscles frequently atrophy (burnt-out stage). Factors that worsen the symptoms of MG are emotional stress, systemic illness (especially viral respiratory infections), pregnancy, the menstrual cycle, drugs affecting neuromuscular transmission and fever.

Pathophysiology

Myasthenia affects the postsynaptic neuromuscular junction. The normal neuromuscular junction releases acetylcholine (ACh) in response to stimulation of the motor nerve. ACh is released from the motor nerve terminal in discrete packages called quanta. The ACh quanta diffuse across the synaptic cleft where they bind to receptors on the folded muscle end-plate membrane. This quantum of ACh then causes depolarization of the muscle end-plate region, causing a cascade of reactions that ultimately lead to muscle contraction. In MG, we believe the concentration of ACh receptors on the muscle end-plate membrane is reduced. Some patients also exhibit an attachment of antibodies to the membrane. ACh is released at normal levels, but its effect on the post-synaptic membrane is reduced, thus reducing the chance of any nerve impulse to cause a muscle action.

While the precise mechanism is unknown, the thymus plays some role in the pathogenesis of MG. It's estimated that nearly 75% of MG patients have a degree of thymus abnormality (e.g., hyperplasia in 85% of cases, thymoma in 15% of cases).

Diagnostic procedures

The following tests can help diagnose MG:

* The edrophonlum chloride (Tensilon) test. In this procedure, the patient is given an intravenous dose of edrophonium chloride. If the weakness is due to abnormal neuromuscular transmission, the patient's symptoms will improve. If the symptoms are subtle or if the patient doesn't respond, he or she may respond to intramuscular neostigmine due to the longer duration of action. Intramuscular neostigmine is particularly useful in young patients such as infants, whose response to intravenous edrophonium chloride may be too brief for adequate observation. In rare cases, a therapeutic trial of daily oral pyridostigmine may produce improvement in patient symptoms that weren't apparent after a single dose of edrophonium chloride or neostigmine. As with many other diagnostic procedures, a positive response for this test is not pathognomic for MG. In particular, patients with amyotrophic lateral sclerosis will usually also respond to edrophonium with increased strength.