ABSTRACT: The goal of this study was to estimate the accuracy of

concentric-needle single-fiber electromyography (CN-SFEMG) for the diag-

nosis of myasthenia gravis (MG). A consecutive series of patients referred
for CN-SFEMG was evaluated by an investigator blinded to the results of
CN-SFEMG in order to determine the presence or absence of MG using an
independent reference standard. Sensitivity, specificity, predictive values,
and likelihood ratios were calculated. The study population included 51
patients (21 with MG). CN-SFEMG was normal in 34 patients (67%) and
abnormal in 17 (33%). The sensitivity of CN-SFEMG for the diagnosis of MG
was 0.67 and the specificity was 0.96. The positive likelihood ratio was 16.8
and the negative likelihood ratio was 0.34. The positive and negative pre-
dictive values were 0.93 and 0.76, respectively. These results indicate that
CN-SFEMG showing abnormal jiggle is extremely useful for confirming the
diagnosis of MG, but that CN-SFEMG showing normal jiggle has limited
utility in excluding the diagnosis.
Muscle Nerve 34: 163–168, 2006

CONCENTRIC-NEEDLE SINGLE-FIBER
ELECTROMYOGRAPHY FOR THE
DIAGNOSIS OF MYASTHENIA GRAVIS
MICHAEL BENATAR, MBChB, DPhil, MUSTAFA HAMMAD, MD, and HEIDI DOSS-RINEY, MD

Department of Neurology, Emory University School of Medicine, 1365A Clifton Road NE,
Atlanta, Georgia 30322, USA

Accepted 14 March 2006

Single-fiber electromyography (SFEMG) is a tech-
nique in which the temporal relationship between
the firing of action potentials from a pair of muscle
fibers within the same motor unit is used as a mea-
sure of the variability (jitter) of neuromuscular trans-
mission time. SFEMG typically requires the use of a
specially constructed single-fiber needle electrode
with a small recording surface and is primarily used
to investigate disorders of neuromuscular transmis-
sion such as myasthenia gravis. SFEMG with a single-
fiber electrode (SF-SFEMG) is uncomfortable3 and
time-consuming, and the use of a reusable recording
electrode has raised concern regarding the risk of
transmission of infectious agents such as prion dis-
ease.19 These limitations have prompted several in-
vestigators to evaluate the possibility of using either
a monopolar or concentric disposable needle, with
Abbreviations: ASFAP, apparent single-fiber action potential; CI, confi-
dence interval; CN-SFEMG, concentric-needle SFEMG; EMG, electromyo-
graphy; LR⫺, likelihood ratio negative; LR⫹, likelihood ratio positive; MCD,
mean consecutive difference; MG, myasthenia gravis; MSD, mean sorted
difference; SFEMG, single-fiber EMG; SF-SFEMG, single-fiber needle SFEMG
Key words: concentric-needle SFEMG; likelihood ratio; myasthenia gravis;
sensitivity; single-fiber electromyography; specificity
Correspondence to: M. Benatar; e-mail: michael.benatar@emory.edu
© 2006 Wiley Periodicals, Inc.
Published online 26 April 2006 in Wiley InterScience (www.interscience.wiley.
com). DOI 10.1002/mus.20568
the low-frequency filter raised from 500 Hz to 2 kHz,
to record apparent single-fiber action potentials
(ASFAPs), the firing patterns of which may similarly
provide a measure of the variability (jiggle) of neu-
romuscular transmission.3–5,19,21
The published data, albeit limited, suggest a
good correlation between jiggle analysis with a con-
centric or monopolar needle electrode and jitter
analysis with a single-fiber needle electrode in
healthy subjects and in patients known to have my-
asthenia gravis (MG).3–5,19,21 However, there has
been no formal attempt to estimate the diagnostic
accuracy of concentric-needle SFEMG (CN-SFEMG)
in the population of patients in whom the test is
most likely to be used—patients in whom the diag-
nosis of MG is suspected but not yet confirmed by
other diagnostic methods. The aim of this study was
to estimate the diagnostic accuracy of CN-SFEMG in
the frontalis muscle in this population of patients.
MATERIALS AND METHODS
Study Subjects. Subjects for this study were retro-
spectively identified from the electromyography lab-
oratory database of Emory University. The study pop-
ulation comprised a consecutive series of patients
evaluated with CN-SFEMG between July 2003 and

Concentric-Needle SFEMG in MG MUSCLE & NERVE August 2006 163

March 2005 as part of the diagnostic work-up for
suspected MG. A HIPAA (Health Information Port-
ability and Accountability Act) waiver was obtained
from the Emory University institutional review board
for review of medical records.
SFEMG Recording and Analysis. Volitional CN-SFEMG
in the frontalis muscle was performed using a con-
centric-needle electrode with a recording area of
0.03 mm2 and a Synergy electromyograph (Oxford
Instruments, Eynsham, UK) with low- and high-filter
settings of 2 kHz and 10 kHz, respectively. The
Synergy automatic jiggle meter requires a stable re-
gion on the rising phase of the spikes in order to
measure interpotential intervals. The Synergy system
does not provide a measure of individual spike rise-
time; therefore, only those potentials with a visibly
fast rise-time, a clear separation from baseline, and
an amplitude of at least 50 ␮V were selected for
analysis. Overlapping spikes were discarded. At least
20 different ASFAP pairs were sampled from each
subject and 50 –100 consecutive action potential
traces were recorded for each. The mean value of
consecutive differences (MCD) and mean sorted dif-
ferences (MSD) for each ASFAP pair were calculated
and the smaller of the two values used as a measure
of neuromuscular jiggle. The overall mean jiggle was
calculated by summating the jiggle for each ASFAP
pair and dividing by the total number of ASFAP
pairs. Subjects were labeled as having abnormal neu-
romuscular transmission if the jiggle of more than
10% of muscle-fiber pairs was abnormal or if the
overall mean jiggle was increased on the basis of
published age-adjusted reference data based on mus-
cle-fiber action potentials recorded using a single-
fiber electrode.6
The CN-SFEMG examination was performed ei-
ther by a board-certified electromyographer with 1–2
years of experience with the SFEMG technique or by
a neurophysiology fellow under the supervision of
the more senior electromyographer. The electro-
myographer elicited a brief history and performed a
focused examination prior to the EMG study, but
was otherwise unaware of the results of acetylcholine
receptor antibody assays or Tensilon tests. Several
patients had received an empiric trial of acetylcho-
linesterase therapy that was prescribed by the refer-
ring physician before the patient was seen in the
EMG laboratory, but these agents were always discon-
tinued at least 24 – 48 hours prior to the study.
Reference Standard. The reference or gold stan-
dard used for determining the presence of MG re-
quired that one of the following two criteria be met:
164 Concentric-Needle SFEMG in MG
(1) elevated anti–acetylcholine receptor antibody ti-
ter or (2) sustained clinical improvement in re-
sponse to either acetylcholinesterase inhibitor or im-
munosuppressive therapy as determined by the
patient and treating neurologist. As a result of the
retrospective nature of the study and the fact that
many of the patients referred to our EMG laboratory
for CN-SFEMG do not receive their ongoing care
within our institution, antibody and Tensilon testing
either were not performed or the results were not
available to us. For the same reasons, the details of
clinical follow-up were sometimes unknown. An in-
vestigator blinded to the results of CN-SFEMG used
the reference standard to determine the presence or
absence of MG. Subjects in whom the treating neu-
rologist no longer suspected MG during follow-up
(because of a change in symptom profile or negative
tests results, or because an alternate diagnosis was
made) were classified as not having MG. Subjects for
whom there was insufficient information (e.g., resid-
ual clinical suspicion for MG but with insufficient
follow-up time to determine response to therapy)
were classified as having an uncertain disease status.
Statistical Methods. Two-by-two tables were con-
structed to determine the relative frequencies of
abnormal CN-SFEMG among patients with and with-
out MG. These tables were used to calculate the
sensitivity and specificity for CN-SFEMG. The 95%
confidence intervals (CIs) were calculated using the
exact binomial method. A sensitivity analysis was per-
formed in which the subjects with unknown disease
status were in turn classified as having or not having
MG in order to set “confidence limits” around the
estimates of sensitivity and specificity. The estimates
of sensitivity and specificity were used to calculate
the positive and negative likelihood ratios. Likeli-
hood ratios are useful measures for estimating the
posttest probability of disease. The positive likeli-
hood ratio (LR⫹) is calculated as sensitivity/(1 ⫺
specificity) and represents the ratio of the probabil-
ity of an individual with disease having a positive test
divided by the probability of an individual without
the disease having a positive test. The negative like-
lihood ratio (LR⫺) is calculated as (1 ⫺ sensitivity)/
specificity and represents the ratio of the probability
of an individual with the disease having a negative
test divided by the probability of an individual with-
out the disease having a negative test.8 Likelihood
ratios greater than 10 and less than 0.1 generate
large and often definitive changes from pretest to
posttest probability; likelihood ratios between 5–10
and 0.1– 0.2 lead to moderate changes in pretest to
posttest probability; and likelihood ratios between
MUSCLE & NERVE August 2006

FIGURE 1. Flow diagram outlining the use of the index test
(CN-SFEMG) and the reference standard to determine the pres-
ence or absence of myasthenia gravis.
2–5 and 0.2– 0.5 result in small changes in probabil-
ity. Likelihood ratios between 1–2 and 0.5–1 rarely
alter pretest probability.8
The study design, data collection, and subse-
quent result reporting incorporated guidelines out-
lined by the Standards for Reporting of Diagnostic
Accuracy (STARD) initiative.1 Data were analyzed
using SAS version 8.02 (SAS Institute, Cary, North
Carolina).
RESULTS
Study Participants. The study population com-
prised 51 patients (25 men and 26 women). Subject
flow through the study is summarized in Figure 1.
Median age (interquartile range) was 50 years (36 –
FIGURE 2. Examples of apparent single-fiber action potential pairs recorded with a concentric-needle electrode. (A) Normal jiggle. (B)
Increased jiggle. The trigger gates have been used to exclude apparent single-fiber action potentials with differing morphology.
Concentric-Needle SFEMG in MG
61) for men and 51 years (41– 60) for women. Thirty-
three subjects were referred for evaluation of purely
ocular symptoms and 18 subjects presented with gen-
eralized symptoms. Among the 21 patients diag-
nosed with MG, 13 (62%) were classified as class I
(ocular MG) and 8 (38%) as class II (mild general-
ized MG), using the Myasthenia Gravis Foundation
of America grading system.9 Elevated titers of anti–
acetylcholine receptor antibodies formed the basis
for the diagnosis of MG in 4 patients, with the diag-
nosis based on a favorable response to therapy in the
remaining 17 patients.
Jiggle Analysis. The mean jiggle (⫾ standard devi-
ation) among the 23 subjects without MG was 29.1 ␮s
(⫾ 12 ␮s) and among the 21 subjects with MG was
47.3 ␮s (⫾ 29 ␮s). Among the 4 MG patients with
elevated titers of acetylcholine receptor antibodies,
the mean jiggle (⫾ SD) was 73 ␮s (⫾ 64 ␮s). Exam-
ples of CN-SFEMG recordings are shown in Figure 2.
Test Results and Estimates. CN-SFEMG was normal
in 34 (67%) patients and abnormal in 17 (33%)
(Table 1). CN-SFEMG is estimated to have a sensi-
tivity of 0.67 (95% CI, 0.47– 0.86) for the diagnosis of
myasthenia (ocular and generalized disease com-
bined) and a specificity of 0.96 (95% CI, 0.78 – 0.99)
(Table 2). These estimates of sensitivity and specific-
ity yielded an LR⫹ of 16.8 and LR⫺ of 0.34. The
sensitivity of CN-SFEMG for the diagnosis of gener-
alized MG is 0.75 (95% CI, 0.45–1.00), which is
better than the sensitivity of 0.62 for the diagnosis of
ocular MG (95% CI, 0.35– 0.88). The specificity for
both ocular and generalized MG is 0.96 (95% CI,
MUSCLE & NERVE August 2006 165
 Table 1. Frequency tabulation of CN-SFEMG results.
Myasthenia gravis
Ocular Generalized
CN-SFEMG negative 5 2
CN-SFEMG positive 8 6
Totals 13 8 23
0.78 – 0.99) (Table 2). Inclusion of subjects with un-
known disease status among those with MG reduces
the sensitivity of CN-SFEMG for the combined diag-
nosis of ocular and generalized MG to 0.57 (95% CI,
0.40 – 0.76). Inclusion of subjects with an unknown
status among those without MG reduces specificity to
0.90 (95% CI, 0.75– 0.99). The positive predictive
value of CN-SFEMG for the diagnosis of MG is 0.93
and the negative predictive value is 0.76.
DISCUSSION
This study has examined the diagnostic accuracy of
volitional CN-SFEMG examination of the frontalis
muscle in a population of patients in whom the
diagnosis of MG was suspected clinically. This test
was found to have a sensitivity of 67% and a speci-
ficity of 96%, and LR⫹ and LR⫺ were 16.8 and 0.34,
respectively, indicating that an abnormal test result
(i.e., abnormal jiggle) results in a large and often
definitive change from pretest to posttest probability
of MG, but that a negative test result produces only
a modest reduction in probability of the disease.
Perhaps more important given the nature of the
study population is the finding that the positive and
negative predictive values of CN-SFEMG for the di-
agnosis of MG are 93% and 76%, respectively. These
results suggest that an abnormal CN-SFEMG is ex-
tremely useful for supporting or making the diagno-
sis of MG, but that a negative or normal result does
not preclude the diagnosis.
A sensitivity of 67% is reasonably good considering
the population examined in this study, but it is substan-
tially lower than that observed in prior studies of the
diagnostic accuracy of SFEMG. The reasons for the
discrepancy between these estimates of the sensitivity
Table 2. Accuracy of CN-SFEMG for the diagnosis of myasthenia gravis.
N Sensitivity Specificity
All MG 21 0.67 0.96
Ocular MG 13 0.62 0.96
Generalized MG 8 0.75 0.96
MG, myasthenia gravis; PPV, positive predictive value; NPV, negative predictive value.
166 Concentric-Needle SFEMG in MG
No myasthenia gravis Unknown Totals
22 5 34
1 2 17
7 51
of this test are likely to be found in the differences in
study design between this and prior studies. These
design issues include the patient population studied,
the reference standard used to determine the presence
or absence of MG, the sample size, the threshold used
for designating jiggle as abnormal, the muscle studied,
and the type of needle (concentric or single-fiber)
used to measure jiggle/jitter.
The most obvious difference between our study
and previously published studies is that we used a
concentric-needle electrode rather than a single-
fiber electrode to measure apparent single-fiber
muscle action potentials. Critics of this technique
might raise two objections. First, they may question
whether the potentials recorded using a concentric-
needle genuinely represent potentials from single
muscle fibers or whether they represent spike com-
ponents of electrical activity from more than one
muscle fiber. Second, they might point out that we
used normative data based on true single-fiber re-
cordings and that these are of questionable rele-
vance to concentric-needle ASFAP recordings.
There is little evidence upon which to base a re-
sponse to these concerns, but the published litera-
ture suggests a good correlation between jitter mea-
surements with a single-fiber electrode and jiggle
measurements with a concentric or monopolar elec-
trode,3–5,19,21 and the jiggle recorded in this study in
subjects without myasthenia is comparable to that
reported by other investigators in healthy subjects
using single-fiber,2,5 monopolar,3,4 and concentric-
needle electrodes.5,19 It is conceivable that, although
jiggle values might not differ substantially from jitter
values when recorded from normal motor endplates
(given the small range of jitter values under these
PPV NPV LR⫹ LR⫺
93% 76% 16.75 0.34
89% 81% 12.4 0.40
86% 92% 15.0 0.26
MUSCLE & NERVE August 2006
circumstances), increased jitter from an abnormal
motor endplate might be masked by the dominance
of normal motor endplates when recording with a
concentric needle (given the possibility of recording
spike components from more than one muscle fi-
ber). We do not think that there is any way to re-
spond definitively to this objection based on the
available data.
Critics of the use of CN-SFEMG might also point
to the fact that our finding of a sensitivity of 67% is
substantially worse than the sensitivity of SFEMG
performed with a single-fiber electrode. However, all
previous studies of the accuracy of SF-SFEMG for the
diagnosis of MG were characterized by important
methodological shortcomings, and therefore reli-
able estimates of the sensitivity of SFEMG for the
diagnosis of MG are lacking. Most studies of the
utility of SF-SFEMG have been performed in popu-
lations of patients who are already known to have
MG.7,10,14,17 These studies reported that the fre-
quency of abnormal SF-SFEMG in patients with MG
ranges from 79%10 to 95%.17 These estimates of the
sensitivity of SF-SFEMG for the diagnosis of MG are
of questionable clinical relevance because SF-
SFEMG for diagnostic purposes is not typically per-
formed in patients who are already known to have
MG. The inclusion only of patients already known to
have MG represents a form of selection bias known
as spectrum bias in that the study does not include a
certain spectrum of patients (in this case, those with
suspected MG). The result is an inflated estimate of
the sensitivity of the test. Other studies that have
included patients with already confirmed MG are
susceptible to the same bias,12,18 even if healthy sub-
jects or those with other neurological diseases are
also included.
Among studies that have included both patients
with and without MG,11,12,15–17,19,20 in only a select
few has the study population comprised a series of
patients in whom the diagnosis of MG was suspected
and in whom SF-SFEMG was performed as part of
the diagnostic work-up,11,13,15,16,20 and these patients
were consecutive in even fewer studies.15,20 Because
these studies examined the diagnostic accuracy of
SF-SFEMG in the very population in whom the test
would be used in clinical practice (i.e., those in
whom the diagnosis is considered, but not yet
proven), these studies are of the most clinical rele-
vance.
Oey and colleagues reported a sensitivity of
SF-SFEMG of 94%.13 This high sensitivity may at least
in part have resulted from the nature of the criteria
used to define jitter as abnormal. The use of a low
threshold (30 ␮s for each single-fiber pair and 20 ␮s
Concentric-Needle SFEMG in MG
for the overall mean jitter for all pairs combined)
has the effect of increasing sensitivity. The mean age
of patients in their study was 51 years.13 Based on the
published reference values of the Ad Hoc Commit-
tee of the AAEM Single Fiber Special Interest Group,
with correction for the use of stimulated SF-SFEMG
(stimulated SFEMG jitter ⫽ volitional SFEMG jitter/
公2), the upper limit of normal for the jitter of a
single-fiber pair in the orbicularis oculi muscle at
this age is 39 ␮s and the upper limit of normal for
the overall mean jitter is 28.9 ␮s,2,5 suggesting that
Oey et al. set the threshold for defining abnormal
jitter too low. Ukachoke et al. reported a sensitivity
of SF-SFEMG of 87%.20 Similar to the study by Oey et
al., this relatively high sensitivity may have resulted,
at least in part, from the low threshold used to
definite jitter as abnormal. The low threshold in this
study is attributed to the authors’ requirement that
only a single muscle-fiber pair display abnormal jitter
rather than the customary requirement that the jit-
ter of more than 10% of muscle-fiber pairs (i.e., 3
muscle-fiber pairs out of a total of 20) be abnor-
mal.2,5
Rouseev et al. reported a sensitivity of SF-SFEMG
of 100%.16 This estimate was based on the finding of
abnormal SF-SFEMG in only 5 patients with MG. The
limitation of their study is that the diagnosis re-
mained indeterminate in 18 patients. Sensitivity
analysis in which these 18 patients are included
among those with definite myasthenia would reduce
the diagnostic sensitivity to 69%. Specificity in their
study was reported to be 67%, but this would de-
crease to 53% if the 18 patients with an indetermi-
nate diagnosis are included in the group without
MG. The implication of this analysis is that the pre-
cision of the estimates of sensitivity and specificity
are relatively low.
In the study by Padua et al., abnormalities on
SF-SFEMG formed part of the reference standard for
the diagnosis of MG, a source of error known as
incorporation bias.15 Use of the test whose diagnos-
tic accuracy is under investigation as a component of
the reference standard has the effect of increasing
the estimate of the test’s sensitivity. These investiga-
tors reported that SFEMG has a sensitivity of 100%
and is therefore probably an overestimate.
The spectrum of patients included in our study,
with inclusion of those with milder disease and a
high proportion of seronegative subjects, may also
have contributed to the relatively low sensitivity we
observed. In this regard it is relevant to note that
jiggle was abnormal in all seropositive myasthenics
and that the jiggle among the 4 patients with ele-
vated anti–acetylcholine receptor antibody titers
MUSCLE & NERVE August 2006 167
(73 ⫾ 64 ␮s) was substantially higher than that
among the seronegative population (47.3 ⫾ 29 ␮s).
Although SF-SFEMG is commonly thought to
have extremely high sensitivity for the diagnosis of
MG, a careful review of the literature indicates that
prior studies have likely overestimated its sensitivity
based on the study design employed. Our study de-
sign has a number of strengths. We studied a con-
secutive series of patients referred for CN-SFEMG as
part of the diagnostic evaluation for possible MG.
The examiner was unaware of the final diagnosis,
and the reference standard for defining the pres-
ence of MG was not susceptible to the incorporation
bias that would result from using the results of CN-
SFEMG to define the presence of disease. The judg-
ment about the presence or absence of MG based on
the reference standard was made by an investigator
blinded to the results of CN-SFEMG. The commonly
accepted definition of abnormal jitter was used,
which requires that greater than 10% of muscle-fiber
pairs show abnormal jitter or that the overall mean
jitter for all 20 pairs is abnormal. Age- and muscle-
adjusted reference values were used to define jiggle
as abnormal. For all these reasons it is likely that our
estimate of the sensitivity of CN-SFEMG for the di-
agnosis of MG is more accurate than prior reports
despite the use of a concentric needle to measure
jiggle in the frontalis muscle, although this conclu-
sion must be tempered by the potential limitations of
CN-SFEMG recordings.
The results of our study indicate that concentric-
needle SFEMG is useful as part of the evaluation of
patients in whom MG is suspected but unproven by
other diagnostic tests. Concentric-needle SFEMG in
this patient population has a sensitivity of 67% and a
specificity of 96%. Whether the diagnostic yield
would be improved by using a single-fiber electrode
will require an investigation in which both types of
recording needle electrodes are used in an appro-
priate study population.
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