Neuromuscular Disorders

Neuromuscular disorders consist of conditions affecting any major component of the motor unit: motor neuron, peripheral nerve, neuromuscular junction, and muscle. Neuropathies may involve all components of the nerve, thereby producing sensory, motor, and autonomic dysfunction, or only one component. Myopathies may involve only the proximal or distal muscles, or both.

Myasthenia gravis (also see Chapter 13 ) is a disorder of the muscular system caused by partial blockade or destruction of nicotinic acetylcholine receptors by IgG antibodies. This syndrome is characterized by fluctuating ophthalmoplegia, ptosis, and bulbar, respiratory, or limb weakness and is confirmed by a beneficial response to cholinergic drugs. ^{[664] [665]} These patients often have other autoimmune diseases, including rheumatoid arthritis and hypothyroidism. Thirty-three percent of patients with myasthenia gravis have bulbar symptoms (and are therefore subject to problems with disposal of secretions) at initial evaluation, and more than 60% of people with myasthenia gravis will have bulbar symptoms at some time during their life. This symptom should not be confused with respiratory muscle weakness, which occurs much less commonly.

The severity of the disease correlates with the ability of antibodies to decrease the number of available acetylcholine receptors.^[664] Treatment of myasthenia is usually begun with anticholinesterase drugs, but in moderate and severe disease, treatment progresses to steroids and thymectomy.^{[664] [665]} Immunosuppressive drugs and plasmapheresis are initiated if the more conservative measures fail, and intravenous immunoglobulin, a rapid-onset therapy, is reserved for acute exacerbations and myasthenic crises. ^{[664] [665]}

One major problem for the anesthesiologist involves the use of muscle relaxants and their reversal.^[666] Because much of the care of myasthenia gravis patients involves tailoring the amount of anticholinesterase medication to the maximal muscle strength of the patient, derangement of the course of the patient during surgery could necessitate reassessment of the drug dosage. For that reason, several researchers recommend withholding all anticholinergic drugs for 6 hours before surgery and reinstituting medication postoperatively with extreme caution because the sensitivity of these patients to such drugs may have changed. In addition, there has been some concern that anticholinergic drugs may lead to a high incidence of bowel anastomotic leaks in patients who have undergone bowel anastomosis. Small doses of succinylcholine can be used to facilitate endotracheal intubation; tiny doses of nondepolarizing drugs can be used for intraoperative relaxation not achieved by regional anesthesia or volatile anesthetics. Controlled ventilation is usually required for at least 24 to 48 hours postoperatively.^{[665] [666] [667]} This practice is especially important in cases involving myasthenia gravis of more than 6 years' duration, chronic obstructive lung disease, daily pyridostigmine requirement of 750 mg in association with significant bulbar weakness, and vital capacity of less than 40 mL/kg.^[667]

Lambert-Eaton syndrome (myasthenic syndrome) is characterized by proximal limb muscle weakness and is associated with antibodies directed against the voltagegated calcium channels in presynaptic nerve terminals. Strength or reflexes may increase with repetitive effort. Affected patients have decreased release of acetylcholine at the neuromuscular junction. Guanidine therapy enhances the release of acetylcholine from nerve terminals and improves strength. Men who have this syndrome generally have small cell carcinoma of the lung or other malignancy, whereas women often have malignancy, sarcoidosis, thyroiditis, or a collagen-related vascular disease. In addition, these patients have increased sensitivity to both depolarizing and nondepolarizing muscle relaxants.^[668] Lambert-Eaton syndrome is also associated with an autonomic nervous system defect manifested by gastroparesis, orthostatic hypotension, and urinary retention.

Dermatomyositis and polymyositis are characterized by proximal limb muscle weakness with dysphagia. These conditions are associated with malignancy or collagen-related vascular disease and often involve respiratory and cardiac muscle.

Periodic paralysis is another disease in which sensitivity to muscle relaxants increases. Periodic weakness starts in childhood or adolescence and is precipitated by rest after exercise, sleep, cold, surgery, or pregnancy. Hypokalemic and hyperkalemic forms exist and are associated with cardiac arrhythmias. Like thyrotoxic periodic paralysis,

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Muscular dystrophy patients now survive into their late twenties or early thirties. Complicating their disease are respiratory infections, kyphoscoliosis, muscle contractions, and cardiac abnormalities. Duchenne's muscular dystrophy, the most common of the muscular dystrophies, is a sex-linked recessive disease involving the Xp21 locus.^[672] It occurs after 2 years of age, at which time patients experience a rapid progression of muscle disease that leads to incapacity in their teens. Cardiac involvement is common when the disease affects the proximal and pelvic muscles, and respiratory failure is a frequent cause of death. Limb-girdle muscular dystrophy is not as severe as Duchenne's muscular dystrophy; it occurs later in life, has cardiac involvement, and is transmitted as an autosomal recessive trait. Facioscapulohumeral muscular dystrophy (FSHMD) is a disease of autosomal dominant inheritance that has a mild clinical form in adolescence. Patients with FSHMD have a normal life span without an increased risk of cardiac complications; however, postoperative respiratory deaths have been recorded. Myotonic dystrophy is a disease in which continued active contraction of muscles persists after voluntary effort or stimulation has ceased. This autosomally dominant inherited disease begins at 20 to 40 years of age and is associated with cardiomyopathy, baldness, testicular atrophy, cataracts, intellectual and emotional abnormalities, and premature death in the 50- to 60-year-old range. The facial, sternocleidomastoid, distal, and pharyngeal muscles become weak and atrophy. Because the disease involves the muscles themselves and not their innervation, conduction anesthesia cannot produce adequate relaxation of tonic muscles. Gastric dilation has also been reported to be a problem, as has malignant hyperthermia. As with the other forms of muscular dystrophy, most problems in myotonic dystrophy arise from cardiac arrhythmias and inadequacy of the respiratory muscles.^[672] For all the forms of muscular dystrophy, as for all the neuropathies (discussed earlier), there have been problems related to exaggerated serum potassium release after the administration of depolarizing muscle relaxants (also see Chapter 13 ).

Malignant hyperthermia (also see Chapter 29 ) in the patient or in a relative of the patient merits careful history taking and at least consideration of performing a test for susceptibility to the condition (see Chapter 25 ). Prophylaxis with intravenous dantrolene sodium (Dantrium) may also be warranted (also see Chapter 29 ). In some cases, malignant hyperthermia has been associated with recognizable musculoskeletal abnormalities such as strabismus, ptosis, myotonic dystrophy, hernias, kyphoscoliosis, muscular dystrophy, central core disease, and marfanoid syndrome. Appropriate preparation for a patient with previous masseter spasm, or trismus, is a matter of considerable debate. We prepare for malignant hyperthermia (i.e., we ensure a contaminant-free machine, use nontriggering agents, and have a malignant hyperthermia cart in the room) but do not routinely perform muscle biopsy or prescribe dantrolene prophylaxis. ^{[673] [674]} Malignant hyperthermia occurs most frequently in children and adolescents, the incidence being 1 in 14,000 administrations of anesthetic. The incidence increases to 1 in 2500 patients requiring squint surgery. Questions to ask parents during the preoperative evaluation include the following: "Does your child become rigid when upset?" and "Does your child sweat profusely when upset?" However, the sensitivity and specificity of such questions in predicting malignant hyperthermia have not been confirmed. The hope is to soon have a genetic screening test to detect most forms of malignant hyperthermia, but as yet such a test remains an unrealized promise. The reader is referred to Chapter 25 and Chapter 29 for a complete discussion of the screening procedure to use.