Case 21

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.



QUESTIONS



1. The abnormalities seen on routine nerve conduction studies in this case are least often observed in:
A. Amyotrophic lateral sclerosis.

B. Myopathy.

C. Lambert-Eaton myasthenic syndrome.

D. Postpoliomyelitis syndrome.

2. Characteristics of this disorder include all of the following except:
A. It results from impaired release of acetylcholine from the presynaptic terminal.

B. It is caused by blockage of the voltage-gated calcium channel (VGCC) in the presynaptic terminal.

C. It usually manifests with generalized weakness and minimal extraocular muscle weakness.

D. It frequently is associated with thymoma.

3. Both myasthenia gravis and Lambert-Eaton myasthenic syndrome (LEMS) result in:
A. Low-amplitude compound muscle action potentials (CMAPs).

B. Significant facilitation of CMAPs after brief exercise.

C. Decrement of CMAPs with slow repetitive stimulation.

D. Significant increment of CMAPs with rapid repetitive stimulation.



Case 21: Nerve Conduction Studies

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Case 21: Needle EMG

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EDX FINDINGS AND INTERPRETATION OF DATA


Relevant EDX findings in this case include:


1. Low CMAP amplitudes with normal distal latencies and conduction velocities throughout the upper and lower limbs.

2. Normal sensory nerve action potentials (SNAPs) throughout.

3. Normal needle EMG.

4. Prominent postexercise potentiation of all motor amplitudes (i.e., CMAPs) after a single stimulus following brief exercise (10 seconds). This facilitation was universal (i.e., it occurred when applied to all motor nerves studied) and ranged from 260 to 300%. These postexercise potentiation values are as follows:

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5. Prominent CMAP increment after rapid repetitive stimulation (30 and 50 Hz) of the left median nerve at 250% (Figure C21-2).

6. A decrement of the CMAP after slow repetitive stimulation of the left median nerve at 35%.

7. Normal needle EMG.

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Figure C21-1 Baseline compound motor action potentials (CMAPs) with superimposed postexercise CMAPs of the left median nerve, recording the abductor pollicis brevis (A), and the left ulnar nerve, recording the abductor digiti minimi (B). Note the prominent facilitation following 10 seconds of exercise (260% for median and 294% for ulnar).


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Figure C21-2 Rapid, repetitive stimulation (50 Hz) of the median nerve at the wrist, recording the abductor pollicis brevis in a normal control (top), and in this patient (bottom). Note the significant facilitation of compound motor action potential (CMAP) (250%) in the patient but not the control.


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 of LEMS is highly dependent on the electrophysiologic characteristics of the neuromuscular junction defect. Also, anti-P/Q-type VGCC antibodies are detected in the serum of 90% of patients with LEMS who have SCLC and in less than 50% of patients with LEMS without cancer. Elevated titers are detected in more than 10% of patients with SCLC and paraneoplastic cerebellar degeneration with no LEMS manifestations. Low titers may also be present in patients with other autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis. All patients with LEMS should be screened for cancer, particularly lung cancer, by CT scan or magnetic resonance imaging (MRI) of the chest.


Treatment of LEMS is difficult. Treatment of the primary cancer is essential but seldom results in improvement of the neurologic symptoms. Figure C21-5 outlines a practical algorithmic treatment plan of weakness for patients with LEMS. Measures to combat weakness include:


1. Drugs, such as pyridostigmine (a choline esterase inhibitor), guanidine, or 3-4 aminopyridine. 3-4 Aminopyridine blocks voltage-sensitive potassium channels, thereby increasing evoked transmitter release by prolonging the action potential duration and increasing calcium influx at the nerve terminal. Potential side effects include paresthesias and seizures. It is available commercially in Europe but limited to research studies in the United States. Guanidine also enhances the release of ACH from presynaptic terminal, but its serious adverse effects, including hepatotoxicity and bone marrow suppression, are limiting factors.

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Aug 12, 2016 | Posted by in CARDIOLOGY | Comments Off on Case 21

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