The “myasthenic” disorders all share the primary characteristic of muscle weakness that fluctuates in severity and recovery. These diseases target the three components of synaptic transmission in the neuromuscular junction: presynaptic region, synaptic basal lamina, and postsynaptic receptors. The underlying defects are either autoimmune or genetic in nature.
Myasthenia gravis (MG), the most common of the myasthenic diseases, is a chronic antibody-mediated autoimmune disease. Most patients have immunoglobulins that are directed against the α-subunit of nicotinic acetylcholine receptor (nAChR). Destruction of these receptors by circulating antibodies leads to a functional decrease in the number of nAChRs. Seronegative patients, however, do not have detectable anti-nAChR antibodies. This group usually has antibodies directed against muscle-specific receptor tyrosine kinase (MuSK) which mediates agrin-induced clustering of nAChRs. Diagnosis of MG is confirmed by a transient improvement in muscle strength after the intravenous injection of edrophonium, an acetylcholinesterase inhibitor. MG patients often have other autoimmune diseases, such as diabetes mellitus, thyroid disease, and systemic lupus erythematosus. Antibodies can transfer from a myasthenic mother to the fetus, causing neonatal MG.
The clinical hallmark of MG is generalized muscle weakness and rapid fatigability of voluntary skeletal muscles with repetitive use. Partial recovery occurs at rest. Physical examination shows normal reflexes, sensation, and coordination. MG seems to affect those skeletal muscles (extraocular, pharyngeal, and laryngeal) innervated by the third, ninth, and tenth cranial nerves. Symptoms such as diplopia, ptosis, dysarthria, and dysphagia are often the presenting complaints. Weakness of the limb muscles occurs in a proximal to distal distribution. As the disease progress, involvement of the diaphragm and accessory muscles of the neck increases the risk of respiratory crises (Table 116-1). In patients with MG, disease activity fluctuates between periods of exacerbation and remission. For instance, noncompliance with medications, infection, and other physiologic stressors (temperature, pregnancy, surgery, emotional stress) may result in fulminant exacerbation.
TABLE 116-1Classification of Myasthenia Gravis ||Download (.pdf) TABLE 116-1 Classification of Myasthenia Gravis
|Type ||Category ||Presentation |
|I ||Ocular ||Ptosis, diplopia |
|IIa ||Mild generalized ||Ocular involvement, extremity weakness, no bulbar signs |
|IIb ||Moderately severe generalized ||More severe ocular or bulbar signs, variable limb muscle involvement, no crises |
|III ||Acute fulminating ||Rapid onset of severe bulbar and skeletal weakness with respiratory involvement |
|IV ||Late severe ||Generalized and prominent bulbar signs and crises, severe MG developing >2 years after symptom onset |
Pyridostigmine, an acetylcholinesterase inhibitor, is the primary pharmacologic therapy for MG. By increasing the amount of acetylcholine in the neuromuscular junction, this drug increases the likelihood of successful synaptic transmission. Its duration of action is about 3–6 hours. Pyridostigmine is a quaternary amine that does not cross the blood–brain barrier and has fewer muscarinic side effects compared to other cholinesterase inhibitors. The maximal dosage of pyridostigmine rarely exceeds 120 mg every 3 hours. Overdosage can induce more muscle ...