We studied a patient with no prior history of neuromuscular disease who became virtually quadriplegic after parenteral magnesium administration for preeclampsia. The serum magnesium concentration was 3.0 mEq/L, which is usually well tolerated. The magnesium was stopped and she recovered over a few days. While she was weak, 2-Hz repetitive stimulation revealed a decrement without significant facilitation at rapid rates or after exercise, suggesting postsynaptic neuromuscular blockade. After her strength returned, repetitive stimulation was normal, but single fiber EMG revealed increased jitter and blocking. Her acetylcholine receptor antibody level was markedly elevated. Although paralysis after magnesium administration has been described in patients with known myasthenia gravis, it has not previously been reported to be the initial or only manifestation of the disease. Patients who are unusually sensitive to the neuromuscular effects of magnesium should be suspected of having an underlying disorder of neuromuscular transmission. Key words: magnesium myasthenia gravis preeclampsia neuromuscular junction repetitive stimulation MUSCLE & NERVE 13~708-712 1990
MYASTHENIA GRAVIS PRESENTING AS WEAKNESS AFTER MAGNESIUM ADMINISTRATION ROBERT G. BASHUK, MD, and DAVID A. KRENDEL, MD
Magnesium can produce neuromuscular blockade at toxic levels, and patients with disorders of neuromuscular transmission are particularly sensitive. We report a patient with no prior history of neuromuscular disease in whom transient severe weakness after parenteral magnesium administration prompted investigation leading to the diagnosis of myasthenia gravis. CASE PRESENTATION
A 19-year-old primigravida at term was admitted in labor on September 9, 1986. Her prenatal course had been unremarkable and there was no personal or family history suggestive of neuromuscular disease. Forty-five minutes after an uncomplicated delivery, her blood pressure increased from 138190 to 160/100. Because of this and mild pedal edema, From Emory University School of Medicine, Department of Neurology, Atlanta, Georgia. Presented at the annual meeting of the American Association of Electromyography and Electrodiagnosrs, October 17, 1987, San Antonio, Texas. Address reprint requests to Dr. Bashuk, 3910 Austell Road, Austell, Georgia 30001 Accepted for publication September 23, 1989.
CCC 0148-639x190/080708-05 $04 00 0 1990 John Wiley & Sons, Inc.
708
Magnesium in Myasthenia
magnesium sulfate was begun according to a protocol used for preeclampsia. This consisted of 4 grams intravenously over 20 minutes, followed by 5 grams intramuscularly every 4 hours for 6 doses. Ten to 15 minutes after the first dose of magnesium sulfate, she experienced weakness of all extremities. After each subsequent dose, the weakness increased until after the fifth dose, she was almost quadriplegic. Three-and-one-half hours after the fifth dose she was seen in neurological consultation. Her mental status was normal. There was mild bifacial weakness without ptosis. Extraocular movements and pupils were normal. Movement of the tongue and palate were normal. She had mild weakness of neck flexion. There was severe (2/5) proximal weakness in all extremities and mild (4/5) weakness of the distal muscles. Deep tendon reflexes were brisk and symmetrical and plantar responses were flexor. Sensation was normal. T h e serum magnesium level was 3.0 mEq/L (normal = 1.5-2.5 mEq/L). Serum creatine kinase, potassium, sodium, urea nitrogen, creatinine, glucose, TSH, T 4 index and complete blood count were normal. No further magnesium was administered, and there was gradual improvement in her strength.
MUSCLE & NERVE
August 1990
Ten hours after the last dose, there was mild (4/5) proximal muscle weakness and she was able to walk. T h e next day, the proximal weakness was barely detectable and she was discharged one day later. She was seen in the outpatient neurology clinic one month later. She had no complaint of weakness or fatigue and her strength was normal. Several weeks later, she developed weakness in the lower extremities after walking approximately 50 yards. She sat on a curb for several minutes and strength returned. Several days afterwards, examination revealed mild fatigable weakness of the orbicularis oculi and proximal muscles of both upper extremities. She was placed on pyridostigmine 60 mg tid and reported a marked increase in strength and energy. While she was hospitalized, her acetylcholine receptor antibody level was 46 nmol/L (Smith Kline Bio-Science Laboratories, Tucker, Georgia) (normal d0.5 nmol/L). Repeated levels 1 and 2 months later were 84 and 83, respectively. Antibody to striated muscle was not detected.
A
A
...*.
C
ELECTROPHVSIOLOQICSTUDIES
Electrophysiologic studies were performed using a TECA-42 electromyograph (TECA Corp, Pleasantville, NY), 8%~hours after her last injection of magnesium sulfate. Sensory nerve conductions were normal. The median motor nerve conduction velocity was 54 m/sec and the initial amplitude of the compound muscle action potential (CMAP) was 11.5 mV recorded at the abductor pollicis brevis. Repetitive stimulation of the left median nerve at 2 Hz revealed a 22% decrement in amplitude of the initial negative component of the CMAP between the first and the fourth potentials. This was abolished immediately after exercise and increased to a maximum of 50% two minutes after exercise (Fig. 1). The amplitude of the CMAP was 8% higher immediately after exercise than it had been prior to exercise. EMG of the left vastus lateralis and deltoid revealed brief, easily recruited motor units that were unstable and dropped out with sustained effort. There was no abnormal spontaneous activity. Single fiber EMG (SFEMG) revealed markedly increased jitter and blocking in the extensor digitorum communis and mildly increased jitter in the frontalis. Jitter was not quantified. Firing rate had no consistent effect on the jitter. On the following day, repetitive stimulation of the left median nerve at 2 Hz revealed a 16% dec-
Magnesium in Myasthenia
FIGURE 1. Repetitive stimulation of the left median nerve at 2Hz (A) before exercise, (B) immediately after exercise and (C) 2 minutes after exercise.
rement in amplitude of the CMAP between the first and fourth potentials, which was reduced to 14% immediately after exercise, and increased to a maximum of 31% one minute after exercise. There was a 14% postexercise facilitation in aniplitude. Rapid stimulation of the left median nerve (10, 20, and 50 Hz) revealed a decrementing response, but this was not quantified. Increased jitter and blocking was noted in the left biceps but not measured. Follow-up studies were performed 6 weeks later when she was asymptomatic and had strength. Repetitive stimulation of the left median nerve at 2 Hz before and after exercise was normal. EMG demonstrated a few brief myotonic discharges in several muscles, but motor unit potentials and recruitment were normal. SFEMG of the left frontalis demonstrated increased jitter in 8
MUSCLE i 3 NERVE
August 1990
709
Z
s
rn a
MG
MG- Myasthenia gravis LES-Lambert-Eaton syndrome
3.0
LES
Streibg Present Report
3.1 1.4
~~
MG MG ? LES
~
(mEq/L)
M g + + level
Cohen et al’ George & Hahn4 Swift” Gutmann & Takamori’
Reference
Underlying disorder of neuromuscular transmission
~~~
Normal
Low Low
Initial CMAP (amplitude)
No
-
Yes Yes
Post-exercise tetanic facilitation
Yes
Yes -
Decrement with slow repet stimul
-
No No No No, but CMAP amplitude increased
Rapid improvement with IV Ca++
-
-
No
Yes Yes, but incomplete
Improvement with edrophonium
Table 1. Comparison of reports of magnesium-inducedweakness in patients with disorders of neuromusculartransmission.
3 days 2 days
1 minute 5 days 3 days 2 days
Recovery
(67%) of 12 fiber pairs, with blocking in 5 (42%). The average mean consecutive difference (jitter) was 99 microseconds (normal
MYASTHENIA GRAVIS PRESENTING AS WEAKNESS AFTER MAGNESIUM ADMINISTRATION ROBERT G. BASHUK, MD, and DAVID A. KRENDEL, MD
Magnesium can produce neuromuscular blockade at toxic levels, and patients with disorders of neuromuscular transmission are particularly sensitive. We report a patient with no prior history of neuromuscular disease in whom transient severe weakness after parenteral magnesium administration prompted investigation leading to the diagnosis of myasthenia gravis. CASE PRESENTATION
A 19-year-old primigravida at term was admitted in labor on September 9, 1986. Her prenatal course had been unremarkable and there was no personal or family history suggestive of neuromuscular disease. Forty-five minutes after an uncomplicated delivery, her blood pressure increased from 138190 to 160/100. Because of this and mild pedal edema, From Emory University School of Medicine, Department of Neurology, Atlanta, Georgia. Presented at the annual meeting of the American Association of Electromyography and Electrodiagnosrs, October 17, 1987, San Antonio, Texas. Address reprint requests to Dr. Bashuk, 3910 Austell Road, Austell, Georgia 30001 Accepted for publication September 23, 1989.
CCC 0148-639x190/080708-05 $04 00 0 1990 John Wiley & Sons, Inc.
708
Magnesium in Myasthenia
magnesium sulfate was begun according to a protocol used for preeclampsia. This consisted of 4 grams intravenously over 20 minutes, followed by 5 grams intramuscularly every 4 hours for 6 doses. Ten to 15 minutes after the first dose of magnesium sulfate, she experienced weakness of all extremities. After each subsequent dose, the weakness increased until after the fifth dose, she was almost quadriplegic. Three-and-one-half hours after the fifth dose she was seen in neurological consultation. Her mental status was normal. There was mild bifacial weakness without ptosis. Extraocular movements and pupils were normal. Movement of the tongue and palate were normal. She had mild weakness of neck flexion. There was severe (2/5) proximal weakness in all extremities and mild (4/5) weakness of the distal muscles. Deep tendon reflexes were brisk and symmetrical and plantar responses were flexor. Sensation was normal. T h e serum magnesium level was 3.0 mEq/L (normal = 1.5-2.5 mEq/L). Serum creatine kinase, potassium, sodium, urea nitrogen, creatinine, glucose, TSH, T 4 index and complete blood count were normal. No further magnesium was administered, and there was gradual improvement in her strength.
MUSCLE & NERVE
August 1990
Ten hours after the last dose, there was mild (4/5) proximal muscle weakness and she was able to walk. T h e next day, the proximal weakness was barely detectable and she was discharged one day later. She was seen in the outpatient neurology clinic one month later. She had no complaint of weakness or fatigue and her strength was normal. Several weeks later, she developed weakness in the lower extremities after walking approximately 50 yards. She sat on a curb for several minutes and strength returned. Several days afterwards, examination revealed mild fatigable weakness of the orbicularis oculi and proximal muscles of both upper extremities. She was placed on pyridostigmine 60 mg tid and reported a marked increase in strength and energy. While she was hospitalized, her acetylcholine receptor antibody level was 46 nmol/L (Smith Kline Bio-Science Laboratories, Tucker, Georgia) (normal d0.5 nmol/L). Repeated levels 1 and 2 months later were 84 and 83, respectively. Antibody to striated muscle was not detected.
A
A
...*.
C
ELECTROPHVSIOLOQICSTUDIES
Electrophysiologic studies were performed using a TECA-42 electromyograph (TECA Corp, Pleasantville, NY), 8%~hours after her last injection of magnesium sulfate. Sensory nerve conductions were normal. The median motor nerve conduction velocity was 54 m/sec and the initial amplitude of the compound muscle action potential (CMAP) was 11.5 mV recorded at the abductor pollicis brevis. Repetitive stimulation of the left median nerve at 2 Hz revealed a 22% decrement in amplitude of the initial negative component of the CMAP between the first and the fourth potentials. This was abolished immediately after exercise and increased to a maximum of 50% two minutes after exercise (Fig. 1). The amplitude of the CMAP was 8% higher immediately after exercise than it had been prior to exercise. EMG of the left vastus lateralis and deltoid revealed brief, easily recruited motor units that were unstable and dropped out with sustained effort. There was no abnormal spontaneous activity. Single fiber EMG (SFEMG) revealed markedly increased jitter and blocking in the extensor digitorum communis and mildly increased jitter in the frontalis. Jitter was not quantified. Firing rate had no consistent effect on the jitter. On the following day, repetitive stimulation of the left median nerve at 2 Hz revealed a 16% dec-
Magnesium in Myasthenia
FIGURE 1. Repetitive stimulation of the left median nerve at 2Hz (A) before exercise, (B) immediately after exercise and (C) 2 minutes after exercise.
rement in amplitude of the CMAP between the first and fourth potentials, which was reduced to 14% immediately after exercise, and increased to a maximum of 31% one minute after exercise. There was a 14% postexercise facilitation in aniplitude. Rapid stimulation of the left median nerve (10, 20, and 50 Hz) revealed a decrementing response, but this was not quantified. Increased jitter and blocking was noted in the left biceps but not measured. Follow-up studies were performed 6 weeks later when she was asymptomatic and had strength. Repetitive stimulation of the left median nerve at 2 Hz before and after exercise was normal. EMG demonstrated a few brief myotonic discharges in several muscles, but motor unit potentials and recruitment were normal. SFEMG of the left frontalis demonstrated increased jitter in 8
MUSCLE i 3 NERVE
August 1990
709
Z
s
rn a
MG
MG- Myasthenia gravis LES-Lambert-Eaton syndrome
3.0
LES
Streibg Present Report
3.1 1.4
~~
MG MG ? LES
~
(mEq/L)
M g + + level
Cohen et al’ George & Hahn4 Swift” Gutmann & Takamori’
Reference
Underlying disorder of neuromuscular transmission
~~~
Normal
Low Low
Initial CMAP (amplitude)
No
-
Yes Yes
Post-exercise tetanic facilitation
Yes
Yes -
Decrement with slow repet stimul
-
No No No No, but CMAP amplitude increased
Rapid improvement with IV Ca++
-
-
No
Yes Yes, but incomplete
Improvement with edrophonium
Table 1. Comparison of reports of magnesium-inducedweakness in patients with disorders of neuromusculartransmission.
3 days 2 days
1 minute 5 days 3 days 2 days
Recovery
(67%) of 12 fiber pairs, with blocking in 5 (42%). The average mean consecutive difference (jitter) was 99 microseconds (normal
