Original Contribution
Lambert–Eaton Myasthenic Syndrome:
Ocular Signs and Symptoms
Jeffery D. Young, MD, Jacqueline A. Leavitt, MD
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Background: To evaluate ocular signs and symptoms in
Lambert–Eaton myasthenic syndrome (LEMS) and deter-
mine the frequency of ophthalmic involvement.
Methods: A retrospective review of the medical records of
all patients diagnosed with LEMS at the Mayo Clinic in
Rochester, MN, from January, 1976, to December, 2010,
was performed with special attention to ophthalmic symp-
toms and signs.
Results: One hundred seventy-six patients met the inclu-
sion criteria. Ophthalmic symptoms included ptosis in 41
(23%), diplopia in 36 (20.5%), decreased vision in 24
(14%), and dry eye complaints in 12 (7%). Ophthalmic signs
included ptosis in 45 (26%), abnormal ocular motility in 15
(8.5%), strabismus in 14 (8%), pupillary dysfunction in 12
(7%), and findings consistent with dry eyes in 4 (2%).
Conclusions: A significant number of patients reported
ophthalmic symptoms, and many had objective findings on
clinical examination consistent with these symptoms. To
our knowledge, this is the largest case series of ophthalmic
findings in patients with LEMS and indicates that these
patients warrant a complete ophthalmic examination.
Journal of Neuro-Ophthalmology 2016;36:20–22
doi: 10.1097/WNO.0000000000000258
© 2015 by North American Neuro-Ophthalmology Society
T he first known case of myasthenic syndrome in asso-
ciation with lung cancer was published by Anderson
Department of Surgery (JDY), Division of Ophthalmology, Univer-
sity of Vermont College of Medicine, Burlington, Vermont; and
Department of Ophthalmology (JAL), Mayo Foundation, Mayo
Clinic, Rochester, Minnesota.
Supported in part by an unrestricted grant from Research to Prevent
Blindness, New York and The Robert R. Waller Career Development
Award.
The authors report no conflicts of interest.
This study was reviewed and approved by the Institutional Review
Boards of the Mayo Clinic and Olmsted Medical Group. This study
was performed in accordance with HIPAA regulations and was in
adherence with the tenets of the Declaration of Helsinki.
Address correspondence to Jeffery D. Young, MD, University of
Vermont Medical Center, 58 E. View Lane, Berlin, VT 05641; E-mail:
jeffery.young@uvmhealth.org
20
Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.
et al (1) while Lambert et al (2) characterized the
electrophysiologic pattern of this syndrome. Further research
led to the discovery of the autoantibodies thought to be
responsible for the characteristic clinical findings. Lam-
bert–Eaton myasthenic syndrome (LEMS), which includes
both paraneoplastic and autoimmune etiologies, com-
monly involves weakness of the proximal muscles, auto-
nomic symptoms (e.g., decreased sweating and dry
mouth), and reduced deep tendon reflexes. Involvement
of the visual system is less well characterized. Ophthalmic
symptoms, generally mentioned in other studies, have
been reported with a prevalence ranging from 0% to
80% (3,4). The aim of our study was to further elucidate
the ophthalmic symptoms and findings of LEMS.
METHODS
The records of all patients with the diagnosis of LEMS from
January 1, 1976, to December 31, 2010, were reviewed.
Inclusion criteria were clinical features including reduced
deep tendon reflexes, autonomic symptoms (dry mouth,
constipation, impaired sweating, and impotence), and
proximal muscle weakness. In addition, we required
a diagnostic electromyography (EMG) (consisting
of .10% decrement of compound muscle action potentials
at 2 Hz stimulation and facilitation of .100% after brief
exercise or 50 Hz stimulation) and/or the presence of
voltage-gated calcium channel antibodies, N-type or P/Q-
type. Historical information and examination findings were
obtained from the medical record. Each patient’s record was
reviewed with special attention to ophthalmologic and neu-
rologic examination findings. At a minimum, each patient
had a neurologic examination, which included a basic eye
examination including eyelid position, ocular motility, and
pupillary testing.
RESULTS
The diagnosis of LEMS was mentioned in 241 records, and
176 met our inclusion criteria. Men represented 53.3% of
Young and Leavitt: J Neuro-Ophthalmol 2016; 36: 20-22

the patients, and mean age at diagnosis was 60.3 years
(range: 7–83 years). Malignancy was diagnosed either
before diagnosis or during the follow-up period in 79 pa-
tients (44.9%), 65 of which were found to have small cell
lung carcinoma.
Forty-two patients (24%) had an examination by an
ophthalmologist at the time of presentation or during the
follow-up period (up to 14.5 years). Twenty-five patients
(14%) had onset of ophthalmic symptoms coincident with
onset of systemic symptoms. Six patients (3%) had
ophthalmic symptoms (3 with ptosis, 2 with diplopia, and
1 with decreased/blurred vision) before systemic symptoms.
The most common ophthalmic complaints were ptosis and
diplopia with 41 patients (23%) and 36 patients (20.5%),
respectively. Less frequently, 24 patients (14%) reported
decreased vision, and 12 patients had symptoms of dry eye.
Ophthalmic signs included ptosis in 45 patients (26%),
which was asymmetric in 21 patients. Two patients each
had fatigable ptosis and Cogan lid twitch. Motility
dysfunction was noted in 15 cases (8.5%). Two patients
had generalized decrease in motility, and 2 had eye
movements described as dysconjugate. One patient was
noted to have slow horizontal saccades, and 1 patient had
findings of bilateral adduction weakness. Fourteen cases
(8%) had some form of strabismus: esodeviation (4–18
prism diopters), exodeviation (4–10 prism diopters), and
hyperdeviation (2–12 prism diopters). Additionally, 2 pa-
tients showed signs of convergence insufficiency.
Pupillary abnormalities were detected in 12 patients (7%),
including 7 with sluggish pupils. Anisocoria was noted in 4.
One patient was noted to have Horner syndrome, and
another showed hypersensitivity to 0.125% pilocarpine.
Clinical signs of dry eye (staining with vital dyes or
superficial punctate keratitis) were seen in 4 patients (2%).
Because of lack of standardized best-corrected visual
acuity data, findings of blurred or decreased vision could
not be accurately analyzed.
Two patients also were diagnosed with myasthenia gravis
(MG). One of these patients had a positive edrophonium test
before confirming the diagnosis of LEMS with an EMG. The
second patient had acetylcholine receptor binding antibodies
detected at the same time of LEMS diagnosis and sub-
sequently had a positive edrophonium test.
DISCUSSION
Previous studies have shown that eyelid findings in LEMS
are quite common with a range of 28%–54% of patients
(5–7). Ptosis was the most common finding in our cohort
and was generally mild. Brazis (8) identified enhanced
ptosis in 1 patient with LEMS. Breen et al (9) reported
a case of lid elevation on sustained upgaze and suggested
that this may represent facilitation of the levator, similar to
the facilitation seen in other muscle groups in LEMS.
Young and Leavitt: J Neuro-Ophthalmol 2016; 36: 20-22
Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.
Original Contribution
Cogan lid twitch seen in 2 of our patients is likely non-
specific (10,11).
Abnormalities in eye movements in our patients were
generally mild and did not seem to have common pattern.
Findings ranged from an isolated functional deficit to
dysconjugate eye movements. Using quantitative oculog-
raphy, Cruciger et al (12) and Dell’Osso et al (13) showed
that facilitation can occur in extraocular muscles. Three
studies (4–6) comprising 170 patients with LEMS docu-
mented ocular motility abnormalities in up to 30% of pa-
tients. Individual case reports are rare. Kanzato et al (14)
described a 57-year-old man with bilateral ophthalmopare-
sis sparing abduction in both eyes. Rudnicki (15) reported
a 52-year-old woman who noted diplopia on lateral gaze,
but a clear description of her eye movements was lacking.
Diplopia as a symptom of LEMS has been reported in
21%–52% of patients (4,5,7,16–19). Objective signs of
ocular misalignment have been reported to occur in
12%–50% in studies with 227 and 10 patients, respectively
(4–7). Our data showed a lower prevalence with objective
findings. Krieger and Goldchmit (20) reported 2 patients
with isolated medial rectus weakness as the only ocular
manifestation of LEMS. Both were successfully treated with
strabismus surgery. None of our patients required strabis-
mus surgery to treat their deviation.
Pupillary dysfunction in LEMS is an indicator of
intraocular autonomic dysfunction. The most common
sign of pupillary dysfunction in our study was sluggish
pupils. O’Neill et al (5) reported that 6 of their 50 patients
had sluggish pupillary light response, and 2 were noted to
have postganglionic denervation hypersensitivity with
response to dilute cholinergic agonists indicating parasym-
pathetic dysfunction. The patient with LEMS described by
Kanzato et al (14) exhibited Horner syndrome with hyper-
sensitivity to alpha agonist drops demonstrating involve-
ment of the sympathetic pupillary pathway. Clark et al
(21) prospectively evaluated 13 eyes of patients with LEMS
and found evidence of both sympathetic and parasympa-
thetic denervation hypersensitivity in 4 of 7 patients, indi-
cating generalized autonomic dysfunction. They
additionally found abnormal pupil cycle time, a nonspecific
indicator of pupillary reflex arc dysfunction, in 9 of 13 eyes.
Another ocular indicator of autonomic function is ocular
surface lubrication. Dry eye is difficult to quantify as some
patients exhibiting subjective symptoms have no objective
findings on clinical examination. Previous studies indicate
that between 4% and 29% of patients complain of
symptoms of dry eye (7,17,19). Clark et al (21) prospec-
tively tested the reflex tear production in 7 patients with
LEMS (13 eyes) and found that 9 eyes had abnormal
results.
LEMS and MG may occur in the same patient, and
there can be considerable overlap in the clinical eye findings
(22–25). The distribution of muscle weakness in LEMS is
certainly different from MG; in MG, weakness develops in
21
 Original Contribution
a craniocaudal direction and in the opposite direction in
LEMS (3). Although extraocular motor symptoms are more
common in MG, autonomic symptoms (specifically pupil-
lary involvement and dry eye) are not a part of the MG
symptom complex (26).
Our study is limited by its retrospective nature, and most
of the patients were examined by a specialist in neurology
and not ophthalmology. As a tertiary medical center, the
studied patient population may have been biased. Follow-
up was also limited.
This is the largest single-institution series of patients
with LEMS and to the best of our knowledge, the only large
series focusing on ophthalmic symptoms and findings.
Patients with LEMS may present with ophthalmic symp-
toms as part of the initial symptom complex and can very
rarely manifest with ophthalmic symptoms before the onset
of systemic symptoms (15,27). Titulaer et al (17) showed
that ophthalmic findings occur soon after the diagnosis but
not necessarily as soon as other symptoms such as proximal
weakness. Some of our patients had been followed elsewhere
before definitive diagnosis at our institution, resulting in
their presentation later in the clinical course. Therefore,
we could not further define ocular manifestations based
on the chronicity of the disease.
STATEMENT OF AUTHORSHIP
Category 1: a. Conception and design: J. D. Young and J. A. Leavitt;
b. Acquisition of data: J. D. Young; c. Analysis and interpretation of
data: J. D. Young. Category 2: a. Drafting the article: J. D. Young; b.
Revising it for intellectual content: J. D. Young and J. A. Leavitt.
Category 3: a. Final approval of the completed article: J. D. Young
and J. A. Leavitt.
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