Myasthenia gravis and lambert-eaton myasthenic syndrome

Published on 07/02/2015 by admin

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Myasthenia gravis and lambert-eaton myasthenic syndrome

Alaric C. LeBaron, MD

Myasthenia gravis

The incidence of myasthenia gravis (MG), an autoimmune disease of the neuromuscular junction, is 1:20,000 in the adult population and higher in patients with other autoimmune diseases, such as thyroiditis and rheumatoid arthritis. Characterized by weakness of voluntary skeletal muscle, MG can be classified by age, etiology (Table 172-1), or the presence or absence of bulbar signs and symptoms because the muscles innervated by the cranial nerves are most frequently involved (Table 172-2).

Table 172-1

Subgroups or Types of Myasthenia Gravis

Type	Description
Nonimmune
Congenital myasthenic syndrome	Defects in proteins at the neuromuscular junction
Immune
Neonatal myasthenia gravis	Transplacental passage of AChR antibodies
Juvenile myasthenia gravis	Onset before 18 years of age
Early-onset myasthenia gravis	Onset at 18 to 50 years of age
Late-onset myasthenia gravis	Onset after 50 years of age
Seronegative myasthenia gravis	No detectable AChR antibodies

AChR, Acetylcholine receptor.

Table 172-2

Signs and Symptoms Associated with the Classes of Myasthenia Gravis

Class	Signs and Symptoms
I	Any ocular muscle weakness
	May have weakness of eye closure All other muscle strength is normal
II	Mild weakness affecting other than ocular muscles May also have ocular muscle weakness of any severity
III	Moderate weakness affecting other than ocular muscles May also have ocular muscle weakness of any severity
IV	Severe weakness affecting other than ocular muscles May also have ocular muscle weakness of any severity
V	Defined by requirement for intubation, with or without mechanical ventilation, except when used during routine postoperative management

Pathophysiology

Circulating antibodies to acetylcholine (ACh) receptors (AChRs), which are found in 70% to 90% of patients with MG, are thought to reduce the number of functional AChRs via three different mechanisms: competitive blockade of AChRs; complement-mediated lysis of the receptor and muscle end plate, resulting in blocked access to the receptor; and increased destruction and decreased production of AChRs. The net effect of these mechanisms is a motor end plate with decreased surface area and decreased functional AChRs (Figure 172-1).

Figure 172-1 Etiologic and pathophysiologic concepts of the neuromuscular junction. (Netter illustration from www.netterimages.com. © Elsevier Inc. All rights reserved.)

Diagnosis

An electromyogram is the most specific test for the establishment of the diagnosis of MG in a patient with compatible symptoms and signs of the disease. Repetitive closely timed stimuli produce fade or progressively smaller or weaker motor responses in the muscle groups being tested. A Tensilon test (which involves administering a small dose of a short-acting acetylcholinesterase drug) is not often performed to establish the diagnosis of the disease but can be helpful in evaluating a patient with MG whose muscle weakness is worse following surgery and anesthesia to differentiate between a myasthenic crisis and a cholinergic crisis.

Treatment

The gold standard for many years for the treatment of MG was the administration of pyridostigmine, an anticholinesterase drug, which increases the amount of ACh available at the neuromuscular junction. Once the cause of the disease became known, immunosuppressive therapy with a corticosteroid, azathioprine, or cyclosporine became common. Approximately 25% of patients with thymomas have MG; because thymectomy often reduces the effect of the disease, this operation is often performed in patients with refractory MG, even if they do not have a thymoma.

A large, randomized, controlled trial should be completed in 2015 that compares thymectomy to thymectomy plus prednisone in patients with MG. In patients with acute severe exacerbations of disease, plasmapheresis and intravenous administration of immune globulin are recommended because their use is associated with rapid improvement in muscle strength.

Anesthetic implications

Preoperative evaluation

The duration, severity, and record of treatment of MG should be evaluated and documented. Patients with more severe disease, in whom the clinician is concerned about the need for postoperative mechanical ventilation, should have maximum inspiratory and expiratory (“bugle”) pressures measured preoperatively to establish a baseline. Postoperative weakness and the requirement for postoperative mechanical ventilation are common, and because the trachea can be intubated without the use of neuromuscular blocking agents (NMBAs), patients should take their normal dose of pyridostigmine the morning of surgery; any alterations in this practice should be discussed with the patient’s neurologist prior to surgery. Patients with MG are more sensitive to the respiratory-depressant effects of opioids and anxiolytics because these patients have reduced ventilatory reserve; therefore, these drugs should be administered with more caution than normal in patients with MG.

Intraoperative management

Neuromuscular blocking agents

Patients with MG have a relative resistance to the effects of depolarizing NMBAs with unpredictable responses because of decreased AChRs. Required doses of succinylcholine are usually two to three times normal, which increases the risk of a phase 2 block developing. Conversely, patients with MG are very sensitive to the effects of nondepolarizing NMBAs, often requiring as little as one tenth the normal dose, independent of the severity of the patient’s symptoms and signs of disease. Most anesthesia providers, therefore, prefer to avoid the use of NMBAs in patients with MG and, if compelled to use an NMBA, use a low dose of a short-acting or intermediate-acting drug. Although sugammadex has not been approved in the United States, multiple case reports have been published of its use to reverse the effects of NMBAs in patients with MG. It is doubtful, however, that the current practice of avoiding the routine use of NMBAs in patients with MG will change.

Inhalation and intravenously administered anesthetic agents

Inhalation anesthetic agents cause muscle relaxation in patients without MG but cause profound muscle relaxation in patients with MG. Intravenously administered anesthetic agents (e.g., propofol) have not been shown to have undesirable effects in patients with MG.

Regional anesthetics

To avoid the use of an NMBA, many clinicians prefer using regional anesthetic techniques, when indicated, to anesthetize patients with MG. Because patients with MG have decreased ventilatory reserve, however, the risks and benefits of neuraxial techniques (interscalene nerve blocks, phrenic nerve blockade)—essentially any technique with the potential to affect respiratory muscles—must be weighed carefully. Ester-type local anesthetic agents are degraded by pseudocholinesterase, which is also inhibited by pyridostigmine; if a regional anesthetic technique is chosen, an amide local anesthetic agent would be the preferred drug in a patient with MG who is being treated with an anticholinesterase drug.

Postoperative management

Several factors increase the risk for patients with MG to develop postoperative ventilatory insufficiency: (1) duration of MG greater than 6 years, (2) a history of other chronic respiratory disease, (3) a pyridostigmine dose above 750 mg/day, and (4) a preoperative vital capacity of less than 2.9 L. The need for either mechanical ventilation or intensive monitoring should be anticipated. Other postoperative concerns that may arise are myasthenic crisis, cholinergic crisis (both of which can occur with perioperative changes in anticholinesterase treatment), and residual effects of anesthesia. Postoperative pain control with epidural analgesia has been shown to be of benefit in patients with MG in helping to maintain ventilatory drive.

Lambert-eaton myasthenic syndrome

Lambert-Eaton myasthenic syndrome (LEMS), often confused with MG, is a rare disorder of neuromuscular transmission most often associated with carcinoma of the lung, especially oat cell carcinoma of the bronchus. Antibody-mediated destruction of presynaptic voltage-gated calcium channels leads to deficient release of ACh at the neuromuscular junction, causing muscle weakness. The skeletal muscle weakness associated with LEMS is not reliably reversed with anticholinesterase drugs or corticosteroids. Furthermore, exercise improves, rather than reduces, muscle strength in this condition. Patients with LEMS are very sensitive to the effects of both depolarizing and nondepolarizing NMBAs. The potential for LEMS should be considered in patients with known or probable carcinoma, especially of the lung (Table 172-3).

Table 172-3

Comparison of Lambert-Eaton Myasthenic Syndrome and Myasthenia Gravis

Characteristic	LEMS	Myasthenia Gravis
Manifestations
Areas of weakness	Proximal limbs (legs more than arms)	Extraocular, bulbar, and facial muscles
Response to exercise	Improves strength	Fatigue
Muscle pain	Common	Uncommon
Reflexes	Absent or decreased	Normal
Sex	Male > female	Female > male
Coexisting pathology	Small cell carcinoma of the lung	Thymoma
Response to drugs
Succinylcholine	Sensitive	Resistant
Nondepolarizing NMBAs	Sensitive	Sensitive
Anticholinesterase drugs	Poor	Good

LEMS, Lambert-Eaton Myasthenic syndrome; NMBAs, neuromuscular blocking agents.

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