26. Eaton-Lambert Myasthenic Syndrome
Definition
Eaton-Lambert myasthenic syndrome (ELMS) is an autoimmune disease in which autoantibodies attack the voltage-gated calcium channels (VGCC), thus interfering with the release of acetylcholine at the presynaptic motor nerve terminal. Eaton-Lambert myasthenic syndrome is also known as Lambert-Eaton myasthenic syndrome.
Incidence
The most recent “best” estimate for the occurrence of ELMS is 1:100,000.
Etiology
Patients diagnosed with ELMS usually have some form of cancer, whether or not it has been diagnosed. Clinical manifestations of ELMS typically precede the identification of the form of cancer present. Usually, the cancer is identified within 2 years of the ELMS diagnosis. Evidence accumulating over recent years indicates that active zone particles (AZPs) represent the VGCC and align in regular parallel arrays along the presynaptic muscle membrane. In ELMS patients, divalent antibodies act on the VGCCs, cross-linking these gates and causing disruption of the parallel arrays. This disruption causes AZPs to cluster and ultimately decrease. The process culminates in the characteristic weakness of this disorder.
Carcinomas Associated with Eaton-Lambert Myasthenic Syndrome
• Bladder carcinoma
• Breast carcinoma
• Colon carcinoma
• Gallbladder carcinoma
• Kidney carcinoma
• Lymphosarcoma
• Malignant thymoma
• Prostate carcinoma
• Small-cell lung cancer
• Stomach carcinoma
Signs and Symptoms
• Difficulty chewing
• Difficulty raising the arms
• Diminished or absent deep tendon reflexes
• Diplopia
• Dry eyes
• Dry mouth
• Dry skin
• Dysarthria
• Dysphagia
• Impotence
• Metallic taste
• Myalgia
• Postural hypotension
• Progressive weakness of proximal muscles (especially lower extremities)
• Ptosis
• Waddling gait
Medical Management
Once the diagnosis of ELMS is confirmed, the next action must be an almost exhaustive battery of testing to determine the existence of some form of malignancy. If a malignancy is discovered, the focus of treatment is to eradicate it, which by extension often results in improvement of the weakness of ELMS. If no malignancy is uncovered, the focus should shift to a relatively aggressive immunotherapy to bring about ELMS improvement.
Pharmacologic treatment of ELMS alone is focused on administration of medications that result in increased acetylcholine (ACh) transmission across the neuromuscular junction. The increased ACh transmission can occur as a primary action or a secondary result. The increased transmission can be brought about primarily with a medication that causes increased ACh release at the neuromuscular junction; increased transmission may occur secondarily with a medication that decreases the action of acetylcholinesterase.
If weakness persists, the next step is initiation of aggressive immunotherapy. Either plasma exchange (PX) or high-dose intravenous immunoglobulin gamma (IVIgG) may be utilized first because of the rapid improvement each produces. However, the resultant improvements are short lived. More long-lasting benefits may be achieved by initiation of immunosuppression therapy, most often with prednisone and azathioprine or cyclosporine either singularly or in combination.
Progression of ELMS is predicated on the presence or absence of an underlying malignancy along with the presence and severity of associated autoimmune disease. The severity and distribution of muscular weakness affects the prognosis of the patient as well. Since ELMS almost always leads to discovery of an underlying malignancy, its detection leads to earlier treatment for the resulting malignancy, which improves survival potential.
Complications
Most complications are associated with the therapies used to treat ELMS. Other complications include:
• Ataxia
• Autonomic instability
• Bleeding
• Bone marrow depression
• Cardiac dysrhythmias
• Clotting factors depletion
• Cough
• Diarrhea
• Hypercalcemia
• Insomnia
• Liver failure
• Palpitations
• Peripheral paresthesias
• Renal tubular necrosis
• Seizures
Anesthesia Implications
Patients being treated with guanidine hydrochloride should have preoperative liver function tests, a 12-lead electrocardiogram, and renal function assessment. Each of these organs can be greatly affected by guanidine.
ELMS patients are more sensitive to both depolarizing and nondepolarizing muscle relaxants. ELMS patients being treated with pyridostigmine and 3,4-diaminopyridine (DAP) may not be amenable to antagonism of muscle relaxants at the end of surgery.
ELMS patients have reduced respiratory reserves due to the muscle weakness. As a result, these patients are at greater risk for respiratory failure even with minimal exposure to volatile anesthetics and/or sedation.
Patients receiving prednisone should receive a perioperative dose of hydrocortisone because of the adrenal suppression long-term use of corticosteroids may produce.
For patients who have required multiple plasma exchanges, blood loss may be disproportionate to the surgical procedure. Bleeding times should be evaluated preoperatively. If these times are excessive, elective surgery should be postponed until therapeutic measures can bring about some correction of clotting factors and bring the bleeding times closer to normal.
