Case 21

Published on 03/03/2015 by admin

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Last modified 03/03/2015

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Case 21

HISTORY AND PHYSICAL EXAMINATION

A 51-year-old, white, previously healthy woman noted a gradual onset of progressive fatigue and general weakness. At first this was attributed to depression, and she was treated in a psychiatric hospital with haloperidol without effect. Within 3 months, her weakness had worsened so that she was unable to walk more than a few steps and could not manage stairs. Weakness was variable, and was much less of a problem in the morning. When the patient was first seen by a neurologist, a diagnosis of myasthenia gravis was made. She was placed on pyridostigmine (Mestinon®), which resulted in some improvement. At that time, a computed tomography (CT) scan of the chest, obtained to look for thymoma, was reported as normal. On questioning, the patient complained of difficulty swallowing, related to dry mouth, intermittent horizontal double vision and drooping of eyelids, and “burning” of the arms and legs. She denied sphincteric symptoms, loss of weight, loss of appetite, or shortness of breath.

Medical history was relevant for long-standing hypertension and hiatal hernia. She underwent an aortic bypass graft for intermittent claudication, cholecystectomy for gallstones, and hysterectomy for fibroid tumor. She had a long history of heavy cigarette use, at least 70 pack-years. She was on pyridostigmine (Mestinon®), captopril (Capoten®), and ranitidine (Zantac®).

Neurologic examination revealed normal mental status. The patient was not in distress and she used a wheelchair. She had mild bilateral ptosis, which was fatiguable on sustained upgaze. Fundi, pupils, extraocular movements, visual fields, and visual acuity were all normal. There was no facial weakness or asymmetry. The tongue was normal. Muscle bulk and tone were normal. She had proximal weakness, worse in the legs (Medical Research Council [MRC] 4/5 in legs and 4+/5 in arms). Deep tendon reflexes were diffusely hypoactive (trace to 1/4). Neither strength nor reflexes were accentuated by brief exercise. Sensation and cerebellar examination were normal. Gait was slow and waddling. Romberg test was negative.

Electrodiagnostic (EDX) studies were performed 24 hours after discontinuation of pyridostigmine (Mestinon®).

Please now review the Nerve Conduction Studies and Needle EMG tables.

EDX FINDINGS AND INTERPRETATION OF DATA

Relevant EDX findings in this case include:

These findings are consistent with presynaptic neuromuscular junction blockade, such as that seen in LEMS. Classic electrophysiologic findings include low CMAP amplitudes, significant facilitation after brief exercise, and prominent increment after rapid repetitive stimulation.

DISCUSSION

Pathophysiology

Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder of the neuromuscular junction, caused by autoantibodies against the presynaptic P/Q type voltage-gated calcium channels (VGCC). The block of VGCCs results in a decrease in calcium influx during depolarization of the presynaptic membrane, and interferes with the calcium-dependent release of acetylcholine (ACH) from its stores in vesicles into the synaptic cleft. Passive transfer of IgG of patients with LEMS to animals produces the same physiologic and morphologic changes as those seen in humans.

Lambert-Eaton myasthenic syndrome is paraneoplastic, associated with small-cell lung cancer (SCLC) in approximately 50% of patients. A significant predictor for developing SCLC in patients with LEMS is smoking at the time of diagnosis. SCLC is commonly detected soon after the onset of LEMS symptoms, but this latency rarely extends beyond five years. Cultured SCLC cells exhibit VGCC activity, suggesting that SCLC cells expresses VGCCs and initiate the autoimmune process. Serum IgG antibodies against P/Q type VGCCs are present in 90% of patients with LEMS with SCLC, and in 3% of patients with SCLC with no neurological symptoms. Other malignancies associated with LEMS are relatively rare, and most have been intrathoracic such lymphoma, thymoma, and carcinoid tumors. The remaining LEMS patients do not have cancer, are usually younger women, and have other autoimmune disorders such as systemic lupus erythematosus, pernicious anemia, and juvenile-onset diabetes mellitus.

Clinical Features

Lambert-Eaton myasthenic syndrome, also referred to as the myasthenic syndrome, affects primarily adults older than 40 years of age, with a slight predilection to men. Patients present with proximal muscle weakness (especially of the lower extremities) and minimal ocular and bulbar weakness, and are susceptible to fatigue. Deep tendon reflexes are characteristically absent or reduced. Autonomic complaints (especially dry mouth) and transient paresthesias may also occur. A helpful and distinctive clinical finding is muscle facilitation: after a brief period (∼10 seconds) of intensive exercise of a muscle, muscle power is much transiently stronger and the deep tendon reflex to that muscle is enhanced. Unfortunately, this sign cannot always be confirmed during bedside evaluation. Figures C21-3 and C21-4 show the common signs and symptoms of LEMS patients, based on series of 50 patients.

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Figure C21-3 Lambert-Eaton myasthenic syndrome. Symptoms during the course of illness in 50 cases.

(Adapted from O’Neil JH, Murray NMF, Newsom-Davis J. The Lambert-Eaton myasthenic syndrome: a review of 50 cases. Brain 1988:11:577–596.)

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Figure C21-4 Lambert-Eaton myasthenic syndrome. Signs during the course of illness in 50 cases.

(Adapted from O’Neil JH, Murray NMF, Newsom-Davis J. The Lambert-Eaton myasthenic syndrome: a review of 50 cases. Brain 1988;11:577–596.)

The disorder may be mistaken for myasthenia gravis or myopathy. However, the diagnosis