Ocular Aspects of Myasthenia Gravis

Jason J. S. Barton, MD, PhD, FRCPC, and Mohammad Fouladvand, MD, Human Vision and Eye movement Laboratory, Departments of Neurology and Ophthalmology, Beth Israel Deaconess Medical Center, Harvard Medical School; and the Department of Biomedical Engineering, Boston University, Boston, Massachusetts.

Semin Neurol. 2000;20(1) 

In This Article

Differential Diagnosis

Most commonly the clinician is faced with a problem of differentiating ocular myasthenia from other common peripheral or central neuropathic conditions, such as the ocular motor palsies. Less commonly, there is confusion with myopathic disorders, chiefly oculopharyngeal dystrophy, myotonic dystrophy, and CPEO. The slowly progressive nature of these conditions, family history in some, and additional systemic features in others, help make the diagnosis. Isolated CPEO without other features of Kearns-Sayre syndrome can occasionally be confused with ocular myasthenia because it too is associated with increased jitter on single-fiber EMG.[61] Deletions on mitochondrial DNA analysis and ragged red fibers on biopsy confirm the diagnosis.

It must also be remembered that there are other disorders that affect the neuromuscular junction.

Lambert-Eaton myasthenic syndrome (LEMS) is less common than myasthenia gravis. It affects adults primarily and males at least twice as frequently as women. Like myasthenia, LEMS is autoimmune in nature, but its antigenic target is presynaptic, not postsynaptic. Morphological studies show reduced density and abnormal distribution of active zone particles on the presynaptic membrane, and the serum has antibodies against voltage-gated calcium channels. Fifty percent of LEMS are paraneoplastic, most often associated with small cell lung carcinoma[109]; in others it is associated with other autoimmune disorders, such as pernicious anemia, autoimmune thyroid disease, and Sjogren's syndrome.

Compared with myasthenia gravis, weakness in LEMS is often less severe and may improve with exertion. Large muscles are affected, with abnormal gait a frequent initial symptom. Ocular signs are rare, but occasional patients note intermittent ptosis and diplopia. Eye movement recordings can show subclinical abnormalities such as hypometric saccades. Ocular signs of postexertional facilitation include lid retraction after prolonged upgaze.[54] Hyporeflexia and autonomic cholinergic disturbances such as dry mouth and impotence are important clues to the diagnosis.

Rapid (20-50 Hz), repetitive stimulation or forceful voluntary contraction causes an increase in the amplitude of the compound muscle action potential. There is increased jitter on single-fiber EMG, but repetitive stimulation decreases jitter in LEMS and increases it in myasthenia gravis.[110] Assays for antibodies against P-type voltage-gated calcium channels are reported to have sensitivity of 85%, and specificity of 100%.[111]

Several rare congenital myasthenic syndromes exist, with inherited defects of pre- or postsynaptic components of the neuromuscular junction.[1] Some such as familial infantile myasthenia and familial limb girdle myasthenia are autosomal recessive, others such as slow channel syndrome are autosomal dominant or sporadic. Most are apparent from birth, although the slow channel syndrome may present in adulthood. Extra-ocular muscle dysfunction is frequent but unlikely to be the sole manifestation. Sophisticated evaluation is often required for diagnosis.

Toxins can impair neuromuscular transmission and cause generalized and ocular symptoms similar to myasthenia. Many of the drugs that exacerbate known cases of myasthenia can produce weakness in individuals with other neuropathic or muscular disorders, including amyotrophic lateral sclerosis, polymyositis, and polio, among others.[112] Vincristine and vinblastine may cause signs of ocular weakness in cancer patients.

Intoxication with organophosphate insecticides causes a cholinergic crisis, presenting as a combination of autonomic and neuromuscular signs. Treatment is with atropine or pralidoxime.

Botulism causes ptosis, diplopia, dysphagia, and generalized weakness. Unlike myasthenia, it also causes blurred vision, nausea, and vomiting. Saccades may show quiver movements.[113] Clues include similar weakness in friends and family members (if they have a common exposure) and signs of cholinergic autonomic hypofunction, including dilated unreactive pupils, urinary retention, and decreased bowel sounds. Increased jitter is seen on single fiber EMG. Treatment is supportive care with antitoxin administration.

The toxins of certain snakes (cobras, kraits, coral snakes, and sea snakes) block acetylcholine receptors and cause bilateral ptosis, extraocular weakness, and dysphagia, followed by increasing bulbar dysfunction and respiratory failure. Patients require supportive care, antitoxin, and possibly acetylcholinesterase inhibitors.

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