5. The initial manifestations of botulism—blurred vision, diplopia, ptosis, strabismus, and ophthalmoparesis—may be mistaken for myasthenia gravis of acute onset. In botulism, however, the pupils are usually large and unreactive, and the eye signs are followed in rapid succession by involvement of bulbar, trunk, and limb muscles.
6. Similarly, the oculopharyngeal-brachial and variants of Guillain-Barré syndrome (GBS) in the early stages have many of the features of myasthenia, including ptosis, that may be partially responsive to anticholinesterase drugs. The loss of tendon reflexes, acral paresthesias, and areflexia, or the development of ataxia in the limbs make the diagnosis of GBS at once apparent and detailed electrophysiologic testing distinguishes the two conditions.
7. Intoxication with organophosphate insecticides, because of their capacity to induce a cholinergic crisis, may be confused with a myasthenic crisis (see further on).
Certain other small clinical points may be helpful in differentiating myasthenia from other diseases that affect the cranial musculature. A hanging jaw and hanging head are indicative of myasthenia, whereas complete or asymmetric facial paresis is typical of GBS. Botulism usually affects the pupillary convergence reaction, and GBS does so only when there is complete internal and external ophthalmoplegia; diphtheria affects mainly the accommodative reaction early on. The question of midbrain stroke as a consequence of basilar artery occlusion arises in a case with total ophthalmoplegia; it should be recalled that the level of consciousness is usually reduced if vertical gaze and pupillary reactions are lost in cases of basilar artery stroke; such is not the case in neuromuscular diseases. The myasthenic syndrome of Lambert-Eaton, discussed further on, only occasionally affects the ocular muscles, but is identified by its other clinical and electrophysiologic features. Ocular paresis, as may occur in nemaline polymyopathy, oculopharyngeal dystrophy, and thyrotoxic ophthalmic disease, come on too slowly in most cases to be confused with myasthenia gravis. On occasion, the eye movements in myasthenia simulate an internuclear ophthalmoplegia or other “central” sign, even to the extent of including nystagmus in an abducting eye.
The treatment of this disease involves the careful use of two groups of drugs—anticholinesterases and immunosuppressants including corticosteroids and in special acute circumstances, plasma exchange and intravenous immune globulin. An elective thymectomy is appropriate in many patients as discussed below. Consensus guidelines for treatment of myasthenia were issued in 2016 (see Sanders et al) but readers are advised to use clinical judgment in each case and consult the literature for newer versions as they appear.
Anticholinesterase drugs The two drugs that give the best results in ameliorating myasthenic weakness are neostigmine (Prostigmin) and pyridostigmine (Mestinon), the latter being preferred by most clinicians and patients. The usual dose of pyridostigmine is 30 to 90 mg given every 6 h (typically a 60-mg pill is tried first); the oral dose of neostigmine ranges from 7.5 to 45 mg given every 2 to 6 h. Extended-action forms of both drugs are available but are given at bedtime mainly to patients who complain of weakness during the night or early morning hours. The dosage of these drugs and their frequency of administration vary considerably from patient to patient, but we agree with Drachman (2003) that the maximal useful dosage of pyridostigmine rarely exceeds 120 mg given every 3 h. Table 46-1 lists the approximate dose-equivalents of these various drugs.