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Eaton-lambert myasthenic syndrome Long-term treatment of three patients with prednisone.

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Eaton-Iambert Myasthenic Syndrome: Long-term
Treatment of Three Patients with Prednisone
Erich W. Streib, MD,” and A. David Rothner, M D t
Three patients with the myasthenic syndrome of Eaton-Lambert (ELS) were treated with prednisone for 6 and 12
months and more than 3 years, respectively. Muscle strength increased considerably in all, reaching a peak after 3 to
4 months, and was accompanied by simultaneous electromyographic improvement. Reduction of prednisone led to
deterioration in all 3 patients; strength was regained when the higher dosage of prednisone was resumed. Prednisone is an alternative form of treatment for ELS, although the mechanism for its action is unclear.
Streib EW, Rothner AD: Eaton-Lambert myasthenic syndrome: long-term treatment of three patients with
prednisone. Ann Neurol 10:448-453. 1981
The myasthenic syndrome of Eaton-Lambert (ELS) ir
an uncommon disorder most often associated with
small cell bronchogenic carcinoma [241. Recent cases
have been reported in which no malignancy was detected after prolonged follow-up. An occasional patient may have a nearly lifelong history of this illness
[361.
Patients with ELS improve slightly when given anticholinesterase inhibitors [ 2 4 ] .Most respond well to
guanidine hydrochloride (GHCl), which increases
the release of acetylcholine (ACh) from nerve terminals at the neuromuscular junction [20, 21, 341. Unfortunately GHCl is a toxic drug associated with
bone marrow depression [26], long-term renal impairment [ 2 ] , and hepatic dysfunction [39]. These
consequences are of special concern when one is
treating patients with ELS who do not have an underlying life-limiting illness. Germine acetate can
improve muscle strength in ELS, but the drug is
poorly tolerated [7]. 4-Aminopyridine increases the
neurally evoked release of ACh from motor nerve
terminals. Its action was more powerful than that of
GHCl when tested in botulinum-intoxicated animals. It has also been used successfully on a shortterm basis in patients with ELS, but its long-term
toxic side effects have not been ascertained [28, 371.
Engel and co-workers [ 13,411 and Calandre et a1 [ 5 ]
each reported a patient with ELS who regained normal muscle strength with steroid treatment. More recently, a patient with ELS treated by plasmapheresis
showed moderate clinical and electrophysiological
improvement [ 101.
We describe three patients with ELS who were
treated with prednisone for long periods. AH imFrom the *Departmenr of Neurology, University of Nebraska
Medical Center, 42nd and Dewey Ave, Omaha, NE 68105, and the
+Department of Neurology (Pediatric Neurology), Cleveland
Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44106.
proved, and electromyographic examination in two
showed enhanced neuromuscular transmission.
Case Reports
Patient 1
A 56-year-old man was evaluated for increasing hoarseness,
difficulty swallowing, slurred speech, arm and leg weakness, and mouth dryness of a year’s duration. He had lost
16 kg without an associated change in appetite.
General physical examination, cognitive functions, and
mood were normal. Cranial nerves were intact. Muscle
bulk was normal. Formal muscle testing against resistance
revealed good strength in the arms. Hip flexion was graded
as 3/5 and distal leg muscles 4/5 on the Medical Research
Council scale. The patient walked with a laboriously slow
waddle and used a cane. Biceps and triceps reflexes were
decreased; knee and ankle reflexes were absent. Plantar responses were flexor. Sensation to pinprick was blunted
over the feet; light touch and vibration sensation was
decreased on the toes.
Electrophysiological studies revealed small amplitudes of
the compound muscle action potentials (CMAPs) as recorded from the hypothenar, thenar, and extensor digitorum brevis muscles o n supramaximal stimulation of the
appropriate nerves. With repetitive stimulation an initial
decremental response was elicited, which was most pronounced with slow rates. After 10 seconds of isometric
exercise, the amplitudes of the CMAPs increased from 300
to 700%. Motor conduction velocity was 51 m/sec for the
median and 4 6 d s e c for the peroneal nerve. The median
evoked digital nerve action potential was decreased in
amplitude but normal in latency; no sural nerve action potential could b e measured.
Results of extensive laboratory studies were normal except for elevated gamma globulins as shown by serum protein electrophoresis and elevated IgG on immunoglobulin
Received July 21, 1980, and in revised form Feb 3, 1981. Accepted for publication Feb 8, 1981.
Address reprint requests
t”
Dr Streib,
448 0364-5134/81/110448-06$01.25 @ 1981 by the American Neurological Association
Amplitude of Compound Muscle Action Potentials of the Hypothenar Ulnar Nerve at Rest
and after Maximal Voluntary Isometric Exercise i n Patient 1
Amplitude of Negative Peak (mV)
5 Sec after
Rest
10-Sec Exercise
Gain
Date
Medication
04/13/75
07/16/75
09/29/75
Mestinon, 6 0 mg qod
GHCI, 32 mglkg for 17 days; Mestinon, 60 mg qid
GHCI, 13 mglkg; prednisone, 8 0 mg qod
for 6 wk; Mestinon, 6 0 mg qid
GHCI, 12 mglkg; prednisone, 80 mg qod;
Mestinon, 6 0 mg qid
Off Mestinon for 4 days
Off GHCl for 44 hr
GHCI, 12 mg; prednisone, 35 mg qod
GHCI, 12 mg; prednisone, 10 mg qod
12/16/75
12/20/75
12/22/75
02/16/76
07/23/76
assay. Searches for an occult malignancy, including
radiological studies of the gastrointestinal tract, sigmoidoscopy, intravenous pyelography, tomograms of the lungs,
and bronchoscopy with sputum cytology, were negative.
After 10 mg of intravenous edrophonium chloride resulted in electromyographic (EMG) and subjective improvement, the patient was treated with pyridostigmine
bromide, 60 mg 4 times a day, with mild benefit. GHCI,
added at slowly increasing doses, resulted in only shortlived improvement. Electromyographic studies after 17
days of treatment with GHCI, 32 mg/kg, did not reveal
changes in either the CMAPs (Table) o r the rate of increment at 40 per second stimulation. Two days after GHCl
was increased to 45 mg/kg, muscle strength and EMG values both improved. The patient was able to climb stairs
without difficulty and to work outdoors for several hours
without undue fatigue. However, his weakness recurred 3
days later.
Side effects of GHCl included mild gastrointestinal
upset at a dosage of 20 mg/kg and limb and perioral paresthesias at 32 mg/kg. At a dosage of 45 mg/kg GHCI,
nausea was constant, and after 3 days coarse tremors developed and the patient became confused and agitated at
night. GHCl was decreased to 14 mg/kg.
Prednisone was given at 100 mg for 3 days and then reduced to 80 mg every other day (Table). There was no initial deterioration and subjective improvement of muscle
strength was noted after about 2 weeks. Knee and ankle
jerks returned after 7 weeks [30, 331. Maximal improvement was reached after 3 to 4 months, especially on days
when prednisone was taken. EMG revealed an increase in
CMAP amplitude at rest and after exercise; it also demonstrated an earlier rise in the incremental response to repetitive stimulation (Table, Fig 1). Discontinuation of
pyridostigmine resulted in only small EMG changes. When
GHCl was withheld for 2 days, the patient became markedly weak and worsened electrophysiologically despite
continuing prednisone therapy.
Twelve months after its initiation, prednisone was discontinued because it was thought that immunosuppression
might activate the growth of an occult malignancy. This resulted in decreasing muscle strength and concomitant
electrophysiological changes (Table, Fig 1). The patient has
1.0
1.0
2.0
6.5
650
7.0
8.0
700
400
3.8
11.0
290
3.0
2.0
2.5
2.2
10.0
8.0
8.5
9.0
330
400
340
410
(s)
been treated with GHCI, 10 to 15 mg/day, for the past 3
years and has been clinically stable. There is no evidence of
an occult malignancy to date. N o serum antibodies to ACh
receptors were found during a recent examination.
Patient 2
A 60-year-old man had a 10-month history of progressive
weakness and fatigability, difficulty focusing his eyes, light
sensitivity, dry mouth, and aching of both legs. These
symptoms were associated with a 14-kg weight loss. There
was no subjective improvement with pyridostigmine, 6 0
mg 4 times a day. The addition of GHCI, 30 mglkglday,
caused nausea, further lessening of muscle strength, and
clinical and laboratory signs of impaired liver function, as
reported previously [39].
General physical examination was unremarkable. The
patient was alert and had good cognitive function. Speech
was mildly hoarse but otherwise normal. Bilateral mild
ptosis was noted. Extraocular movements were full without
nystagmus or double vision. Pupils were 3 mm and round;
light reaction was sluggish. H e was profoundly weak, unable to turn in bed or support his weight on his legs when
helped to an upright position. He could not flex his hips
against gravity. Testing against resistance showed that
shoulder girdle and upper extremity strength were only
mildly impaired. No atrophy or fasciculations were noted.
Areflexia was present. Sensation for all modalities was
normal.
Initial EMG studies revealed a small CMAP varying from
100 to 500 pV when recorded from the extensor digitorum
brevis, anterior tibial, thenar, hypothenar, biceps, and orbicularis oculi muscles on stimulation of the appropriate
nerves. There was a small decremental response with 2 per
second stimulation and marked facilitation after 10 seconds
of isometric exercise, varying from 1,300 to Z,OOO%. The
motor nerve conduction velocities, amplitudes, and latencies of the surd and digital nerve action potentials were
normal. Details on the electrodiagnostic studies have been
reported elsewhere [39al.
Search for an occult malignancy, including roentgenograms of the gastrointestinal tract, bronchoscopy with
sputum cytology, bone marrow aspiration, intravenous
pyelography, and sigmoidoscopy, was negative, as were
Streib and Rothner: Eaton-Lambert Myasthenic Syndrome 449
studies for collagen vascular disease. Serum immunoglobulin assay and thyroid studies were normal. The serum was
negative for antibodies to ACh receptors.
Pyridostigmine was discontinued when the patient was
admitted; there was n o subjective o r clinical change. O n
the sixth hospital day, prednisone therapy was initiated at a
dose of 100 mg daily for 7 days and then decreased to 80
mg daily for 8 days. Prednisone was then slowly decreased
to 80 mg every other day at discharge.
The patient experienced a transient decrease in volume
of speech and intermittent double vision on the second and
third day ofprednisone therapy. On day 17 he could turn
in bed, tolerate several hours in a chair, and support his
weight in an upright position for 1 to 2 seconds. He also
was able to walk from the bed to a chair with help. The
EMG improved concomitantly (Figs 2, 3). Maximal improvement occurred after 3 months of treatment. He was
then able to walk by himself on crutches and made trips in
the family car without undue fatigue. Because of continuing gastrointestinal problems, prednisone was discontinued
after 6 months. This was associated with an increase in
weakness and fatigability. He was unable to walk by himself
or with help, and could sit only for 1 hour in the bedside
chair. Leg pain, present at the initial admission, had returned.
Patient 3
A 161/2-year-old girl had a 6-month history of slowly progressive leg weakness and clumsiness of gait. H e r arms were
not affected. Symptoms were worse late in the afternoon o r
in the evening. There were no other neurological symptoms. Family and past medical history were unremarkable.
General physical examination was normal. Neurological
examination revealed normal mood and intellectual function. Cranial nerve examination was normal. There was
good muscle bulk in all muscle groups. Muscle strength was
decreased proximally greater than distally in the upper and
lower extremities, with the deltoids and biceps judged at
4/5, hip flexors at 315, and anterior compartment muscles at
4/5. Gait was waddling and she was unable to d o a deep
knee bend, nor could she hop o r walk o n her heels. Muscle
stretch reflexes were normal and symmetrical. Sensory examination and cerebellar function were normal.
450 Annals of Neurology Vol 10 N o 5
Pig I . (Patzent I ) Pijt? per ie~ovidJtirtiul~trorio j ulnar nerce,
record1ng hy)othenar mu^ c l e ~ .<.hik u J e jr orti top /dt, trai i ngs
of 7116175, 9129175, 12116175 12i20l75, 2116176, and
7123176 i j e e a h 2 able) (Ctrlibratiwr I s e ~ ,2 or j nzV aJ
noted
Fig 2. (Patient 2) IJlnar rierce ~tirnulation,recording
hypothenar muscleJ. T o p .? tracings from day 1 , bottom 3
tracings from day 18 of prednisone treatment. Tracings a t 10,
20, and 50 per second stimulation, respeciively. (Calibration:
horizontal bar.r indicate 1 second in each tracing; vertical bars
from top t o bottom: 1 mV, 1 mV, 10 mV, 2 mV, 5 mV, and 5
mV.i
EMG studies revealed normal motor nerve conduction
velocities and distal latencies for the peroneal, posterior tibial, ulnar, and median nerves. The amplitudes of the
evoked CMAPs were at the lower border of normal; slow
repetitive stimulation at 2 per second revealed a small decremental response. Digital and sural nerve action potentials were of normal amplitude and latency. Laboratory
workup was negative, including a search for collagen vascular disease; the cerebrospinal fluid was normal.
November 1981
-.
I//////////////////
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//////////////////I
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I/////
/////////I
1"?_
I
I////////////
F i g 3 . (Patient 2) From bottom to top, compound muscle action
potentials before exercise and 2, 7 , 12, 17, 22, and 27 seconds
after 10 seconds of maximal voluntary isometric exercise. Ldt
column, tracings at day 2 of prednisone treatment (vertical bar
= 2 mV, vertical line of dots = 1 msec). Right column, tracings at day 18 of prednisone treatment (horizontal bar = 2
msec, vertical bar = 5 mV).
F i g 4. (Patient 3) Fifty per second stimulation of the ulnar
nerve, recording hypothenar muscles. Tracing is continuous
from top t o bottom. (Time calibration = 1 sec.)
A diagnosis of myasthenia gravis was made. The patient
was given pyridostigmine bromide, 60 mg, and then 90 mg
5 times a day, but she derived no benefit.
Treatment with prednisone was started in slowly increased doses to 60 mg/day, along with pyridostigmine, 60
mg 4 times a day. Three months later muscle strength was
improved; the patient was able to rise from a deep knee
bend and do a sit-up without difficulty. Pyridostigmine was
discontinued and the prednisone was gradually reduced to
20 mg every other day; this has been her dosage for 3 years.
Her muscle strength is nearly normal and she has been fully
employed. Two attempts to reduce prednisone resulted in
increasing weakness each time.
EMG findings 2 years after the onset of symptoms were
similar to those at the initial examination but also included
the following: immediately after 10 seconds of isometric
exercise, the amplitude of the CMAPs, as recorded from
the smdl hand muscles on stimulation of the ulnar and median nerves, increased by about 100%; the decremental response at slow repetitive stimulation could not be repaired
with exercise or edrophonium chloride, 10 mg intravenously; repetitive stimulation at increasing rates revealed
moderate but sustained facilitation (Fig 4). Microelectrode
studies of an intercostal muscle biopsy were performed by
Dr E. H. Lambert. The findings were those seen in the
Discussion
Lambert and associates delineated the clinical and
electrophysiological features of ELS [23-251. Patients present with proximal muscle weakness and increased fatigability. Extraocular and bulbar muscles
frequently are spared or only mildly affected. Muscle
stretch reflexes are decreased or absent. Distal
paresthesias are common, and somatic sensation may
be impaired. Aching of extremity muscles is not uncommon in patients with severe muscle weakness.
Dry mouth is a frequent complaint; more severe
cholinergic dysautonomia may occur [36]. Most of
those affected are middle-age men, but ELS has occasionally been observed in adolescents or children [6,
83. Antibodies to ACh receptors are within the normal range [27].
Pathogenetically, ELS is characterized by decreased release of ACh at presynaptic junctions. The
neuromuscular nerve terminals are predominantly affected, but there is frequently a more generalized
cholinergic dysautonomia in both patients with and
those without tumor [24, 361. Decreased sweating
and salivation could not be explained by end-organ
myasthenic syndrome [23]. N o antibody to human ACh receptor was found in the serum.
Streib and Rothner: Eaton-Lambert Myasthenic Syndrome 45 1
disease 14, 5, 361. Ishikawa et a1 [18] demonstrated a
defect in neuromuscular transmission when extracts
from a small cell carcinoma in a patient with ELS
were added to the bathing solution of a frog nervemuscle preparation, suggesting that the tumor secreted a neuromuscular blocking agent. This, however, does not explain the occurrence of ELS in
patients without underlying tumors or the lack of
improvement of in vitro neuromuscular transmission
after prolonged washing of human muscle from patients with ELS [23, 371.
Although ELS can be suspected clinically, the
diagnosis is made by electrophysioIogical studies [23,
241. Electrodiagnostic features include small amplitudes of the CMAPs evoked by supramaximal
nerve stimuli. A decremental response follows slow
rates of stimulation; various amounts of facilitation
are noted with high stimulation rates or following a
short period of maximal voluntary isometric exercise.
The distal latencies and conduction velocities of
motor axons are normal. The sensory nerve action
potentials are usually of normal amplitude and latency, but occasional amplitudes are small. O n needle
electrode examination one characteristically finds
short-duration motor unit action potentials that wax
and wane. Microelectrode studies in vitro [23] reveal
a small amplitude of the end-plate potential following
nerve stimulation at slow rates; the quantum content
of the end-plate potential is abnormally low at 1 Hz
stimulation. The increase in frequency of the miniature end-plate potential with potassium stimulation is
significantly less than that of normal muscle fibers.
Although it may occasionally be difficult to distinguish between myasthenia gravis and ELS using clinical EMG studies [8, 381, in vitro microelectrode
studies specifically distinguish between the two.
Our first two patients have typical ELS, by both
clinical and EMG criteria. Antibodies to ACh receptors were negative in both. An occult neoplasm could
not be demonstrated during 6 and 2 years of
follow-up, respectively. The youth of the third patient was unusual [6, 141; electromyographically she
had CMAPs with amplitudes at the low border of
normal, and only minor facilitation followed voluntary exercise or high rates of stimulation. The correct
diagnosis of ELS was confirmed by in vitro microelectrode studies of an intercostal muscle biopsy.
The amplitude of the initial CMAP and that obtained after 10 seconds of isometric exercise may
vary because of technical factors, patient fatigue, or
inadequate exercise [3]. Nevertheless, there was sequential EMG improvement and subsequent deterioration during the course of prednisone treatment in
our first patient (Table, Fig 1). EMG studies were
more systematic in the second patient; the decrease
in postexercise fatigue during the first 3 weeks of
treatment was particularly striking (Fig 3). A second
point of caution regarding clinical EMG study of
neuromuscular transmission in ELS is the use of distal
recording and stimulation sites. T o record and
stimulate from proximal sites causes more discomfort
and technical difficulty but would probably reflect
more adequately the change in neuromuscular
transmission in patients with ELS. Repeated microelectrode studies in vitro on intercostal biopsy
specimens would be the ideal, if impractical, approach [12, 23, 371.
Prednisone and adrenocorticotropic hormone may
have a direct action on neuromuscular transmission
[ 1, 3 11. Prednisone increased the miniature end-plate
potential frequency in the phrenic nerve diaphragm
preparation [42]. Treatment with high doses of
steroid hormones increases posttetanic muscle twitch
tension [35] and enhances the facilitatory action of
G H C l on neuromuscular transmission [16]. In experimental studies, the resulting increase of muscle
twitch tension was caused by stimulus-bound repetitive discharges of motor axons [16, 351. In contrast,
Hofmann [ 171 did not find measurable facilitation of
neuromuscular transmission using the phrenic nerve
diaphragm preparation of steroid-treated rats.
In their response to prednisone, our three patients
had a course similar to that encountered in myasthenia gravis [19], suggesting that the mechanism of
improvement may be the same in both disorders. We
speculate that this was caused by immunosuppression
[9, 101, an inference supported by the time course of
improvement and the association of some cases of
ELS with autoimmune disorders [15,29, 32,401. O n
the other hand, the nerve terminals of steroid-treated
animals may reveal variable changes [ 113. This or a
still unknown mechanism may underlie the effects of
prednisone.
The EMG changes recorded during clinical improvement in our patients are identical to those seen
in patients with ELS who respond to GHCl or anticholinesterase medication. We believe that the
clinical improvement in our patients was due to enhanced neuromuscular transmission, although we did
not control for a possible contribution of stimulusbound repetitive discharges of motor axons. Whatever the reasons, the results indicate that prednisone
is an alternative form of treatment in ELS. The
findings in our first patient support the in vitro observations that prednisone may facilitate the action of
GHCl [16]. Combined therapy with the two drugs
might minimize the side effects of either one alone.
Presented in part at the 105th Annual Meeting of the American
Neurological Association, Boston, MA, Sept 8- 10, 1980.
We thank Dr E. H . Lambert for the results of microelectrode
studies on Patient 3, Dr Ronald Youmans for referring Patient
1 and supplying follow-up data, Dr Walter Friedlander for reviewing t h e manuscript, and Linda Harakal for secretarial assistance.
452 Annals of Neurology Vol 10 No 5 November 1981
References
1. Birnberger KL, Riidel R, Struppler A: ACTH and neuromuscular transmission: electrophysiological in vitro investigation
of the effects of corticotropin and an ACTH fragment on
neuromuscular transmission. Ann Neurol 1:270-275, 1977
2. Blumhardt LD, Joekes AM, Marshall J, et al: Guanidine
treatment and impaired renal function in the Eaton-Lambert
syndrome. Br Med J 1946-947, 1977
3. Brown JC, Johns RJ: Diagnostic difficulties encountered in
the myasthenic syndrome sometimes associated with carcinoma. J Neurol Neurosurg Psychiatry 37: 1214-1224,1974
4. Brown JW, Nelson JR, Hermann C: Sjogren’s syndrome
with myopathic and myasthenic features. Bull Los Angeles
Neurol SOC33:9-20, 1968
5. Calandre L, Vallejo AR, Ricoy JR, Trueba JL, Dieger MA:
Sindrome de Eaton-Lambert tratamiento con corticosteroids.
Rev Neurol (Barcelona) 20:17-24, 1977
6. Chelmicka-Schorr E, Bernstein LP, Zurbrugg EB, Huttenlocher PR: Eaton-Lambert syndrome in a 9-year-old girl. Arch
Neurol 36:572-574, 1979
7. Cherington M: Guanidine and germine in Eaton-Lambert
syndrome. Neurology (Minneap) 26944-946, 1976
8. Dahl DS, Sat0 S: Unusual myasthenic state in a teenage boy.
Neurology (Minneap) 24:897-901, 1974
9. Dau P (ed): Plasmapheresis and the Immunobiology of
Myasthenia Gravis. Boston, Houghton Mifflin, 1979
0. Denys EH, Dau PC, Lindstrom JM: Neuromuscular transmission before and after plasmapheresis in myasthenia gravis and
the myasthenic syndrome. In Dau PC (ed): Plasmapheresis
and the Immunology of Myasthenia Gravis. Boston,
Houghton Mifflin, 1979, pp 248-257
11. Engel AG, Lambert EH, Gomez M R A new myasthenic syndrome with end-plate acetylcholinesterase (ACHE) deficiency, small nerve terminals, and reduced acetylcholine release. Trans Am Neurol Assoc 101:ll-15, 1976
12. Engel AG, Lambert EH, Gomez MR: A new myasthenic syndrome with end-plate acetylcholinesterase deficiency, small
nerve terminals, and reduced acetylcholine release. Ann
Neurol 1:315-330, 1977
13. Engel WK, Warmolts JR: Myasthenia gravis: a new hypothesis
of the pathogenesis and a new form of treatment. Ann N Y
Acad Sci 183:72-87, 1971
14. Fenichel GM: Clinical syndromes of myasthenia in infancy
and childhood. A review. Arch Neurol 35:97-103, 1978
15. Gutmann L, Crosby TW,Takamori M, Martin JD: The
Eaton-Lambert syndrome and autoimmune disorders. Am J
Med 53:354-356, 1972
16. Hall ED: Glucocorticoid enhancement of guanidine
neuromuscular facilitation. Exp Neurol 68:58 1-588, 1980
17. Hofmann WW: Antimyasthenic action of corticosteroids.
Arch Neurol 34:356-360, 1977
18. Ishikawa I, Engelhardt JK, Fujisawa T, Okamoto T, Katsuki
H : A neuromuscular transmission block produced by a cancer
tissue extract derived from a patient with the myasthenic syndrome. Neurology (Minneap) 27:140-143, 1977
19. Johns TR: Treatment of myasthenia gravis: long-term administration of corticosteroids with remarks on thymectomy. In
Griggs RC, Moxley RT (eds): Treatment of Neuromuscular
Diseases. Adv Neurol 17:99-122, 1977
20. Kamenskaya MA, Elmqvist D, Thesleff S: Guanidine and
neuromuscular transmission. I. Effect on transmitter release
occurring spontaneously and in response to single nerve
stimuli. Arch Neurol 32:505-509, 1975
21. Kamenskaya MA, Elmqvist D, Thesleff S: Guanidine and
neuromuscular transmission. 11. Effect on transmitter release
in response to repetitive nerve stimulation. Arch Neurol
32:510-518, 1975
22. Kissel P, Schmitt J, Duc M, Duc ML: Myasthenia and
thyrotoxicosis. In Walton JN, Canal N, Scarlato G , et a1 (eds):
Muscle Disease. Amsterdam, Excerpta Medica, 1969, pp
464-48 1
23. Lambert EH, Elmqvist D: Quantal components of end-plate
potentials in the myasthenic syndrome. Ann N Y Acad Sci
183:183-199, 1971
24. Lambert EH, Rooke ED: Myasthenic state and lung cancer. In
Brain RW, Norris FH (eds): The Remote Effects of Cancer on
the Nervous System. New York, Grune & Stratton, 1965, pp
67-80
25. Lambert EH, Rooke ED, Eaton LM, Hodgson CH: Myasthenic syndrome occasionally associated with bronchial neoplasm: neurophysiologic studies. In Viets H R (ed): Myasthenia
Gravis. Springfield, IL, Thomas, 1961, pp 362-410
26. Lambert EH, Howard FM: Complications of guanidine treatment. Presented to the Myasthenia Gravis Foundation, New
York, December, 1972
27. Lindstrom JM, Seybold ME, Lennon VA, Wittingham S,
Duane DD: Antibody to acetylcholine receptor in myasthenia
gravis. Prevalence, clinical correlates, and diagnostic value.
Neurology 26:1054-1059, 1976
28. Lundh H, Nilsson 0,Rosen F: 4-Aminopyridine-a new drug
tested in the treatment of Eaton-Lambert syndrome. J Neurol
Neurosurg Psychiatry 41:1109-1121, 1977
29. Mori M, Takamori M: Hyperthyroidism and myasthenia
gravis with features of Eaton-Lambert syndrome. Neurology
(Minneap) 262382-887, 1976
30. Nilsson 0, Rosen F: The stretch reflex in the Eaton-Lambert
syndrome, myasthenia gravis and myotonic dystrophy. Acta
Neurol Scand 57:350-357, 1978
31. Noble MD, Peacock J H , Lacher JA, Hofmann WW:
Prednisone-neostigmine interactions at cholinergic junctions.
Muscle Nerve 2:155-157, 1979
32. Norris FH: Neuromuscular transmission in thyroid disease.
Ann Intern Med 64:81-86, 1966
33. Oh SJ, Lee YW, Rutsky E: Eaton-Lambert syndrome: reflex
improvement with guanidine. Arch Phys Med Rehabil
58:457-591, 1977
34. Otsuka M, Endo M: The effect of guanidine on neuromuscular transmission. J Pharmacol Exp Ther 128:273-282, 1960
35. Riker WF, Baker T, Okamoto M: Glucocorticoids and mammalian motor nerve excitability. Arch Neurol32:688-694,1975
36. Rubenstein AE, Horowitz SH, Bender AN: Cholinergic
dysautonomia and Eaton-Lambert syndrome. Neurology
29720-723, 1979
37. Sanders DB, Kim YF, Howard JE, Goetsch GA: EatonLambert syndrome, a clinical and electrophysiological study of
a patient treated with 4-aminopyridine. J Neurol Neurosurg
Psychiatry 43:978-985, 1980
38. Schwartz MS, Stalberg E: Myasthenia gravis with features of
the myasthenic syndrome. An investigation with electrophysiologic methods including single-fiber electromyography. Neurology (Minneap) 25:80-84, 1975
39. Streib EW: Reversible hepatic dysfunction owing to guanidine
treatment. Arch Neurol 36:386, 1979
39a. Streib EW: Eaton-Lambert myasthenic syndrome: serial
electromyographic studies during prednisone treatment.
Electromyogr Clin Neurophysiol 21:107-120, 1981
40. Takamori M, Gutmann L, Crosby TW, Martin JD: Myasthenic
syndromes in hypothyroidism: electrophysiological study of
neuromuscular transmission and muscle contraction in two
patients. Arch Neurol 26:326-335, 1972
41. Vroom FQ, Engel WK: Nonneoplastic steroid responsive
Lambert-Eaton myasthenic syndrome. Neurology (Minneap)
19:281, 1969
42. Wilson RW, Ward MD, Johns TR: Corticosteroids: a direct
effect at the neuromuscular junction. Neurology (Minneap)
24 :1091- 1095, 1974
Screib and R o t h n e r : Eaton-Lambert Myasthenic S y n d r o m e
453
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prednisone, treatment, terms, patients, lambert, syndrome, long, myasthenia, eaton, three
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