Electrophysiological and immunological study in myasthenia gravis: diagnostic sensitivity and correlation.

Abstract

To determine the diagnostic sensitivity of repetitive nerve stimulation (RNS), single fiber electromyography (SFEMG) and acetylcholine receptor antibody (AChRAb) in myasthenia gravis (MG), and to compare the degree of SFEMG abnormality between ocular and generalized MG and between seronegative and seropositive patients.
The sensitivities of RNS, SFEMG and AChRAb were estimated. SFEMG abnormality was compared between ocular and generalized MG and between seronegative and seropositive patients.
Abnormal RNS, abnormal SFEMG and AChRAb were detected in 62%, 93% and 38% of 42 ocular, and 80%, 99% and 73% of 70 generalized cases, respectively. The degree of SFEMG abnormality was significantly greater in the generalized than ocular patients and was significantly greater in the seropositive than seronegative patients in both extensor digitorum communis and orbicularis oculi muscles.
SFEMG is a very sensitive and useful test for MG. A correlation between SFEMG abnormality and clinical phenotype or severity and between SFEMG abnormality and AChRAb seropositivity was demonstrated.
The sensitivities of RNS, SFEMG and AChRAb in the diagnosis of MG were documented. The differences in severity between the ocular and generalized MG and between the seronegative and seropositive MG were confirmed and quantitatively determined by SFEMG.

Full text

Page 1

Electrophysiological and immunological study in myasthenia gravis: Diagnostic
sensitivity and correlation
Rawiphan Witoonpanicha,⇑, Charungthai Dejthevaporna, Arporn Sriphrapradangb, Teeratorn Pulkesa
aDivision of Neurology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
bResearch Center, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
a r t i c l e i n f o
Article history:
Accepted 21 February 2011
Available online 17 March 2011
Keywords:
Myasthenia gravis
Diagnostic sensitivity
Electrophysiological study
Immunological study
Correlation
h i g h l i g h t s
? The sensitivities of RNS, SFEMG and AChRAb in the diagnosis of MG were documented.
? SFEMG abnormality correlated with clinical phenotype and AChRAb seropositivity.
? Difference in severity between ocular and generalized MG was confirmed by SFEMG.
? SFEMG demonstrated difference in severity between seronegative and seropositive MG.
a b s t r a c t
Objective: To determine the diagnostic sensitivity of repetitive nerve stimulation (RNS), single fiber elec-
tromyography (SFEMG) and acetylcholine receptor antibody (AChRAb) in myasthenia gravis (MG), and to
compare the degree of SFEMG abnormality between ocular and generalized MG and between seronega-
tive and seropositive patients.
Methods: The sensitivities of RNS, SFEMG and AChRAb were estimated. SFEMG abnormality was com-
pared between ocular and generalized MG and between seronegative and seropositive patients.
Results: Abnormal RNS, abnormal SFEMG and AChRAb were detected in 62%, 93% and 38% of 42 ocular,
and 80%, 99% and 73% of 70 generalized cases, respectively. The degree of SFEMG abnormality was sig-
nificantly greater in the generalized than ocular patients and was significantly greater in the seropositive
than seronegative patients in both extensor digitorum communis and orbicularis oculi muscles.
Conclusion: SFEMG is a very sensitive and useful test for MG. A correlation between SFEMG abnormality
and clinical phenotype or severity and between SFEMG abnormality and AChRAb seropositivity was dem-
onstrated.
Significance: The sensitivities of RNS, SFEMG and AChRAb in the diagnosis of MG were documented. The
differences in severity between the ocular and generalized MG and between the seronegative and sero-
positive MG were confirmed and quantitatively determined by SFEMG.
? 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights
reserved.
1. Introduction
Electrophysiological studies play an important role in the diag-
nosis of myasthenia gravis (MG). Repetitive nerve stimulation
(RNS) which is the most easily and commonly performed test is
not sensitive and is often normal especially in ocular and mild gen-
eralized MG. Single fiber electromyography (SFEMG) is usually
more sensitive both in ocular and generalized cases. Nevertheless,
both tests are not specific and can be abnormal in other conditions
as well. The detection of acetylcholine receptor antibody (AChRAb)
is a more specific tool in the diagnosis of this disease. This study
was aimed to estimate the sensitivity of RNS, SFEMG and AChRAb
in the diagnosis of ocular and generalized MG patients, to compare
the degree of abnormality of SFEMG between the ocular and gen-
eralized MG patients, to compare the SFEMG abnormality in differ-
ent muscles in each group of patients, and to correlate the findings
of electrophysiological study with those of immunological study.
2. Methods
2.1. Patients
This is a prospective study of patients who were clinically diag-
nosed as MG. Patients were consecutively screened as they were
sent for the tests to confirm the clinical diagnosis between May
2005 and January 2009. Patients were included only if (1) they were
diagnosed as MG based on the presence of one or more of the com-
mon clinical features including drooping of eyelid, double vision,
1388-2457/$36.00 ? 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.clinph.2011.02.026
⇑Corresponding author. Address: Division of Neurology, Department of Medi-
cine, Ramathibodi Hospital, Rama 6 Road, Bangkok 10400, Thailand. Tel.: +66 2
2011386; fax: +66 2 3547233.
E-mail address: rarwt@mahidol.ac.th (R. Witoonpanich).
Clinical Neurophysiology 122 (2011) 1873–1877
Contents lists available at ScienceDirect
Clinical Neurophysiology
journal homepage: www.elsevier.com/locate/clinph

Page 2

difficulty in swallowing and proximal limb weakness with or with-
out a history of fatigability, and (2) they had not been on any immu-
nosuppressive drugs before the electrophysiological tests or blood
sampling for AChRAb assay. Associated diseases helped support
the diagnosis, e.g. a history of hyperthyroidism. A positive edropho-
nium test confirmed the diagnosis but a negative test did not ex-
clude it. If there was no symptom or sign of fatigability, a
subsequent response to a cholinesterase inhibitor (pyridostigmine)
orimmunosuppressivedrugswasrequiredtoconfirmthediagnosis.
All patients were followed up on a long-term basis for at least
2 years from the onset of the disease. The patients were grouped
into ocular or generalized MG patients. Ocular MG patients refer
to patients who were suffering from pure ocular MG and were fol-
lowedupforatleast2 yearswithoutprogressiontogeneralizedMG.
This study was approved by the ethics committee of the Faculty
of Medicine, Ramathibodi Hospital, Mahidol University (ID 06-47-
06). Each patient was interviewed and examined, had electrophys-
iological study, and had blood sampled for immunological study
with verbal and written informed consent.
2.2. Electrophysiological study
Both RNS and SFEMG were performed in each patient whose
last dose of pyridostigmine had been taken at least 12 h prior to
the tests. A Dantec Keypoint EMG machine was used in both tests.
2.2.1. RNS
The RNSwas performedbysupramaximally stimulatinganulnar
nerve at the wrist, radial nerve at the elbow, facial nerve in front of
theearandaccessorynerveattheneckat3 Hzbyasurfaceelectrode.
Compoundmuscleactionpotentials(CMAP)wererecordedfromthe
abductordigitiminimi(ADM),extensordigitorumcommunis(EDC),
anconeus, trapezius, nasalis and orbicularis oculi (OO) muscles. A
train of 10 stimuli was delivered to each nerve at rest. The muscle
was then exercised for 1 min after which the nerve was stimulated
immediatelyandat30 s,and1,2,3and4 min.Thepercentagedecre-
mentsofthebaseline-to-peakamplitudeofthefourthCMAPascom-
pared to the first CMAP were used to determine abnormality. A
decrement of 10% or more had been considered as abnormal (Kim-
ura, 1989). In this study, the test was considered abnormal if a dec-
rement of 10% or more was obtained at least twice in at least one
muscle. Most patients had either 4 or 5 muscles tested.
To comparethe relative sensitivity of the tested muscles, the fre-
quency of decremental response was calculated and expressed as
thepercentageoftestedpatientswithdecrementalresponseineach
muscle. In addition, to assess the fatigability of the muscles, the de-
gree of decrement of each muscle was graded as follows: grade
1 = 10–19% decrement, grade 2 = 20–29% decrement, grade 3 = 30–
39% decrement, grade 4 = 40–49% decrement and grade 5 = 50% or
more decrement. In each muscle, the lesser degree between the
twoorthemostreproducibledegreeofdecrementwastakenintoac-
count. The proportion of patients with eachdegreeof decrement(%)
was then calculated for each muscle in generalized and ocular MG.
2.2.2. SFEMG
At the beginning of the study, SFEMG was performed on the EDC
in every patient. Later on, this was changed to the OO for technical
reasons and SFEMG was performed on the OO for the rest of the pa-
tients. Voluntary muscle activation technique was used and 20 sin-
gle fiber potential pairs (or 10 pairs in a few severe cases) were
recorded by a disposible concentric needle electrode (CNE, 25 mm
30 G, Excel Tech Ltd., Canada). The low and high frequency filter
used was 0.5 and 10 kHz, respectively. The potential pairs were se-
lected by both the computerized program and the examiner, and
they had to be distinct individual spikes of well-defined peak and
short rise-time (less than 300 ls) to be accepted. The chosen poten-
tial pairs had a clear separation with an individual amplitude of at
least 200 lV. The mean consecutive differences of successive inter-
potential intervals (MCD or jitter) of each pair and the mean of MCD
of 20 pairs were determined. For each jitter measurement, a mini-
mumof 50 consecutive dischargeswere recorded. The test wascon-
sidered abnormal when the following two parameters were
abnormal: (1) more than 2 potential pairs (10%) had increased jit-
ter; (2) the mean of MCD was abnormal for the patient’s age and
for that muscle according to the published reference values. The
upper limits of mean of MCD values using a single fiber needle elec-
trode (SFNE) for EDC (for age 10–90 years) from 35 to 41 microsec-
onds (ls) and those for OO (for age 10–70 years) from 40 to 43 ls
(Sanders and Stalberg, 1996) were originally applied. Subsequently,
the more recently reported reference values of mean of MCD from
SFEMG study using CNE in voluntarily activated EDC (upper lim-
it = 30 ls) and OO (upper limit = 31 ls) (Kouyoumdjian and Stal-
berg, 2008) were also used to determine the abnormality in all
the patients. The sensitivity obtained from the SFNE reference val-
ues was then compared to that from the CNE reference values.
2.3. Immunological study
A blood sample was taken from each patient for AChRAb assay
at the same time as the electrophysiological tests in most patients.
Some patients had blood sampling before the electrophysiological
tests and the longest interval between the two studies was
2 weeks. AChRAb was detected by a radio receptor assay of IBL Im-
muno Biological Laboratories. Antibody titers of >0.40 nmol/L were
considered positive and indicative of myasthenia gravis. In view of
the fact that the highest standard value provided by the manufac-
ture’s laboratories was limited to 8 nmol/L, all the greater titers
were expressed as a minimum value of >8 nmol/L. Higher dilutions
were required to achieve an accurate value in sera with high titers.
However, those sera were not diluted due to the limitation of the
antigen. Twenty five healthy Thai and 14 Thai patients with other
neurological disorders had blood tested for the antibody and
served as controls.
2.4. Comparing the degree of abnormality of SFEMG between the
ocular and generalized MG patients
The percentage of potential pairs with increased jitter and the
mean of MCD of EDC and OO in ocular and generalized patients
were compared to see if there were any differences in the severity
between both groups.
2.5. Comparing the degree of abnormality of SFEMG between EDC and
OO in ocular and generalized MG patients
In ocular and generalized MG patients, the percentage of poten-
tial pairs with increased jitter and the mean of MCD were com-
pared between the EDC and OO to see if there were any
differences of the abnormality in these 2 muscles in each group.
2.6. Correlating findings of electrophysiological study with those of
immunological study
The percentage of potential pairs with increased jitter and the
mean of MCD of EDC and OO were compared between the seroneg-
ative and seropositive patients and also between patients with
high (>8 nmol/L) and low (>0.4 to 68 nmol/L) AChRAb titers.
2.7. Statistical analysis
The mean and standard deviation (SD) were used to describe
continuous data. Frequency and percentage were used to describe
categorical data. Chi-square tests (or exact test) were used to com-
1874
R. Witoonpanich et al./Clinical Neurophysiology 122 (2011) 1873–1877

Page 3

pare RNS, SFEMG, and AChRAb between ocular and generalized pa-
tients. Independent t tests (or Mann–Whitney test) were used to
compare percentage of potential pairs with increased jitter and
mean of MCD between ocular and generalized patients, to compare
these two parameters between the EDC and OO muscles in ocular
and generalized patients, to compare these two parameters
between seronegative and seropositive patients, and to compare
these two parameters between patients with high and low AChRAb
titers. All analyses were performed using STATA version 11.1. A p
value of less than 0.05 was considered statistically significant.
3. Results
3.1. Patients
A total of 112 patients fulfilled the inclusion criteria and were
included in this study. There were 73 females and 39 males with
a F:M ratio = 1.9:1. The female age range was 15–86 years
(mean ± SD = 45.8 ± 17.0) and the male age range was 21–89 years
(mean ± SD = 48.3 ± 17.5). Among these patients, there were 42
ocular MG with 27 females and 15 males (F:M = 1.8:1), and age
ranging from 16 to 74 years (mean ± SD = 46.9 ± 16.4). The number
of patients with generalized MG was 70 with 46 females and 24
males (F:M = 1.9:1), and age ranging from 15 to 89 years
(mean ± SD = 46.5 ± 17.7).
3.2. Electrophysiological study
3.2.1. RNS
In ocular MG, abnormal RNS was shown in 62% (26/42) of the
cases. Most of the patients (21/26, 81%) had decremental response
in only 1 or 2 muscles and none had abnormal response in all the
muscles tested. The muscles most often affected in those patients
who had abnormal response in only 1 or 2 muscles were the OO
(48%, 10/21) and anconeus (33%, 7/21). The overall decremental re-
sponse was obtained in 37% (15/41), 26% (10/38), 25% (10/40), 24%
(10/41), 14% (3/22) and 8% (1/13) of OO, anconeus, trapezius, nasa-
lis, ADM and EDC muscles tested, respectively.
In generalized MG, abnormal RNS was detected in 80% (56/70)
of the cases. Among the patients who had an abnormal test, the
number of muscles with decremental response varied from only
one to all the muscles tested. Half of the patients (52%, 29/56)
had decremental response in all the tested muscles and 14% (8/
56) had abnormal response in only 1 or 2 muscles. The muscles
most frequently affected in those patients who had abnormal re-
sponse in only 1 or 2 muscles were the nasalis (75%, 6/8) and OO
(50%, 4/8). The overall decremental response was shown in 74%
(51/69), 69% (48/70), 63% (42/67), 58% (14/24), 57% (40/70) and
55% (22/40) in nasalis, OO, anconeus, EDC, trapezius and ADM
muscles tested, respectively.
Most of the times, muscles with decremental response showed
this from the first stimulation before exercise throughout the test.
However, exercise brought about the abnormal response in a num-
ber of occasions. In muscles with pre-exercise decremental re-
sponse, enhancement of the degree of the abnormal response by
exercise was often unremarkable. The degree of decrement varied
among muscles tested in each patient.
Table 1 shows the proportion of patients with each degree of
decrement in each muscle in generalized and ocular MG. In gener-
alized MG, 40–53% of the patients showed grade 5–3 decrements
in nasalis, OO, anconeus, EDC and ADM while grade 2–1 decre-
ments were obtained in the trapezius in the majority of patients.
In contrast, the majority of ocular MG patients showed grade 2–1
decrements in all the muscles. However, a small proportion of pa-
tients showed grade 5 decrements in the anconeus and grade 3
decrements in the OO muscles.
3.2.2. SFEMG
All of the patients had SFEMG performed on one muscle each. In
the ocular MG group, 14 patients (33%) had SFEMG performed on
the EDC and the rest had the OO muscle tested. The abnormal find-
ings were shown in 88% (37/42) of the cases when SFNE reference
values were applied and in 93% (39/42) of the cases when CNE ref-
erence values were used. The positive cases had potential pairs
with increased jitter ranging from 15% to 100% and the mean of
MCD ranging from 35 to 205 ls.
In the generalized MG group, SFEMG was performed on EDC in
23 patients (34%) and on OO in the rest. The abnormal finding was
detected in 99% (69/70) of the cases when either SFNE or CNE ref-
erence values were applied. The positive cases had potential pairs
with increased jitter ranging from 25% to 100% and the mean of
MCD ranging from 46 to 229 ls.
Among the generalized MG patients who were tested negative
for AChRAb, there were five patients who had antibody to muscle
specific tyrosine kinase (MuSKAb). Two of these patients had
SFEMG tested on EDC with 90% and 80% potential pairs with in-
creased jitter, and mean of MCD of 86 and 75 ls, respectively.
Three patients had SFEMG performed on OO with 85%, 60% and
95% potential pairs with increased jitter, and mean of MCD of 97,
69 and 178 ls, respectively.
In performing SFEMG, both the EDC and OO gave good results.
However, it was easier to get motor unit potential pairs and the pa-
tients could tolerate and cooperate better with OO. CNE worked
well without any problems.
3.3. Immunological study
AChRAb was detected in 60% of all the patients with 38% (16/
42) in the ocular and 73% (51/70) in the generalized group. The ti-
ters of antibody varied widely within each group. These ranged
Table 1
Data of RNS showing the proportion of patients with each degree of decrement (%) in each muscle in generalized and ocular MG.
Proportion of patients with each degree of decrement (%)
Generalized MG
Decrement grade
Ocular MG
Decrement grade
n
54321
n
54321
Orbicularis oculi
Anconeus
Trapezius
Nasalis
EDC
ADM
43
34
37
46
20
10
23
26
5
8
25
30
7
6
11
9
10
0
23
15
8
33
5
10
26
29
38
24
25
30
21
24
38
26
35
30
13
9
9
8
2
3
0
11
0
0
0
0
0
0
0
0
0
0
15
0
0
0
0
0
8
33
33
25
100
33
77
56
66
75
0
66
n = number of patients with decremental response in each muscle.
EDC = extensor digitorum communis; ADM = abductor digiti minimi.
grade 1 = 10–19% decrement, grade 2 = 20–29% decrement, grade 3 = 30–39% decrement, grade 4 = 40–49% decrement and grade 5 = 50% or more decrement.
R. Witoonpanich et al./Clinical Neurophysiology 122 (2011) 1873–1877
1875

Page 4

from 0.46 to >8 nmol/L in ocular cases and from 0.7 to >8 nmol/L in
generalized patients. The antibody titers in healthy controls and
patients with other neurological disorders were all negative and
ranged from 0 to 0.1 nmol/L.
In seropositive ocular MG, 44% (7/16) of the patients had anti-
body titers 68 nmol/L and 56% (9/16) had antibody titers
>8 nmol/L. In seropositive generalized MG, 22% (11/51) of the pa-
tients had antibody titers 68 nmol/L and 78% (40/51) had antibody
titers >8 nmol/L. However, these proportions were not significantly
different (p = 0.108).
3.4. Comparing the degree of abnormality of SFEMG between the
ocular and generalized MG patients
The degree of abnormality of SFEMG tended to be more severe
in the generalized than the ocular cases. The mean of the percent-
ages of potential pairs with increased jitter and mean of means of
MCD were significantly greater in the generalized MG than the
ocular MG for both muscles (Table 2).
3.5. Comparing the degree of abnormality of SFEMG between EDC and
OO in ocular and generalized MG patients
The degree of abnormality of SFEMG was not significantly dif-
ferent between EDC and OO in the ocular cases. In generalized
MG, the mean of the percentages of potential pairs with increased
jitter was also not significantly different between EDC and OO but
the mean of means of MCD was significantly greater in the OO than
in the EDC (Table 3).
3.6. Correlating findings of electrophysiological study with those of
immunological study
One of the three ocular MG patients who had normal SFEMG (in
OO) had abnormal RNS (in anconeus and trapezius) and positive
AChRAb, and another one had normal RNS but positive AChRAb.
There was only one ocular patient who had negative results for
all three tests. This patient also suffered from hyperthyroidism
which indirectly supported the diagnosis of MG. The only general-
ized MG patient who had normal SFEMG had normal RNS but po-
sitive AChRAb.
The mean of the percentages of potential pairs with increased
jitter and mean of means of MCD were significantly greater in sero-
positive than those in seronegative patients in both EDC and OO
muscles (Table 4). However, these two parameters were not signif-
icantly different between patients with high titers and those with
low titers of AChRAb in EDC while only the mean of the percent-
ages of potential pairs with increased jitter was significantly great-
er in patients with high titers than those with low titers in OO
(Supplementary Table S1).
4. Discussion
WithregardtoelectrophysiologicalstudyinthediagnosisofMG,
abnormal RNS in even one muscle can be meaningful and this sug-
gests that several muscles should be tested to get an abnormal re-
sponse. In this study, the OO, anconeus, trapezius and nasalis
muscles (in decreasing sensitivity) gave reasonably good yield in
ocular MG (37–24% of each muscle tested) with OO being the most
sensitive. In generalized MG, all tested muscles (nasalis, OO, anco-
neus, EDC, trapezius and ADM) showed a high frequency of decre-
mental response (74–55% of each muscle tested) with nasalis
being the most sensitive. The sensitivity of RNS in the generalized
MG of 80% in this study is comparable to that previously reported
(53–100%), but in the ocular MG of 62% is higher than that reported
before(10–17%)(AAEM,2001).Thishighersensitivitymaybedueto
the fact that several muscles including the facial muscles were
tested in each patient in this study. Exercise also helped increase
thesensitivityofthetest.Althoughthedegreeofdecrementmayde-
pend on the severity of disease and fatigability in general, this did
vary among various muscles tested in each patient. The difference
inthedegreeof decrement ofthese musclesmayreflectthevariable
involvementofeachmuscleinthisdisease.Thesedatatogetherwith
the frequency of decremental response in each muscle can help se-
lect high sensitivity muscles in both ocular and generalized MG.
The sensitivity of SFEMG in this study is comparable to that pre-
viously reported (Meriggioli and Sanders, 2005). In ocular MG, the
sensitivity was 88% when SFNE reference values were applied and
93% when CNE reference values were used. The techniques and the
criteria of accepted potential pairs which were employed in this
study were comparable to those in the referenced study using
CNE except for the low frequency filter which was 0.5 kHz in this
study and 1 kHz in that study (Kouyoumdjian and Stalberg,
2008). The sensitivity was 99% when either SFNE or CNE reference
values were applied. The basis for this finding in generalized MG
was that SFEMG abnormalities in this group of patients were
mostly so severe that they exceeded both the SFNE and CNE refer-
ence values. However, it is certainly more appropriate to use the
CNE reference values in a study with CNE.
Table 2
Comparison of SFEMG abnormality between the ocular and generalized MG patients.
SFEMG parameters
n
Ocular
n
Generalized
p-value
EDC
Pairs with increased
jitter, mean ± SD (%)
Means of MCD,
mean ± SD (ls)
OO
Pairs with increased
jitter, mean ± SD (%)
Means of MCD,
mean ± SD (ls)
14 55.0 ± 23.2 2372.5 ± 19.8 0.020
14 61.5 ± 14.82376.3 ± 15.4 0.007
28 44.1 ± 29.84776.6 ± 25.0<0.001
2869.2 ± 39.1 47114.9 ± 46.4<0.001
Table 3
Comparison of SFEMG abnormality between the EDC and OO muscles in ocular and
generalized MG patients.
SFEMG parameters
n
EDC
n
OO
p-value
Ocular MG
Pairs with increased jitter,
mean ± SD (%)
Means of MCD,
mean ± SD (ls)
Generalized MG
Pairs with increased jitter,
mean ± SD (%)
Means of MCD,
mean ± SD (ls)
1455.0 ± 23.22844.1 ± 29.80.239
1461.5 ± 14.82869.2 ± 39.1 0.364
2372.5 ± 19.847 76.6 ± 25.00.494
2376.3 ± 15.4 47114.9 ± 46.4<0.001
Table 4
Comparison of SFEMG abnormality between seronegative and seropositive MG
patients.
SFEMG parameters
n
Seronegative
n
Seropositive
p-value
EDC
Pairs with increased
jitter, mean ± SD (%)
Mean of MCD,
mean ± SD (ls)
OO
Pairs with increased jitter,
mean ± SD (%)
Mean of MCD,
mean ± SD (ls)
2153.9 ± 16.81681.6 ± 19.5<0.001
2161.8 ± 13.01682.3 ± 13.7<0.001
2448.3 ± 26.651 72.0 ± 30.20.001
2473.7 ± 39.151109.2 ± 49.20.003
1876
R. Witoonpanich et al./Clinical Neurophysiology 122 (2011) 1873–1877

Page 5

In MuSKAb-positive MG patients, the abnormal rates of SFEMG
in EDC varied among reported series with some obtaining signifi-
cantly lower rates than in AChRAb-positive MG patients (Farrugia
et al., 2006; Kuwabara et al., 2007; Nemoto et al., 2005; Stickler
et al., 2005) whereas others did not observe much difference be-
tween these two groups of patients (Oh et al., 2006; Pasnoor
et al., 2010). On the other hand, facial muscles appeared to consis-
tently show higher abnormal rates than EDC (Evoli et al., 2003;
Farrugia et al., 2006; Kuwabara et al., 2007). In this study, there
was no difference which could be observed in performing SFEMG
in patients with MuSKAb from other generalized MG patients.
The reason for the difference in the rates of abnormality in EDC
among the series may have been the difference in the frequency
of involvement of limb muscles as has previously been suggested
(Oh, 2009). However, the abnormal jitter in EDC does not always
go along with clinical weakness of the limb muscles as has been re-
ported before (Nemoto et al., 2005). This discrepancy was also ob-
served in one of our patients who had abnormal SFEMG findings in
EDC but did not have weakness of the limb muscles.
SFEMG is much more sensitive than RNS and if RNS is abnormal,
SFEMG is almost always abnormal. In this study, there was only
one (ocular) case who had abnormal RNS but normal SFEMG find-
ings. Therefore, if the RNS is abnormal, it may not be necessary to
do SFEMG which is much more time consuming and needs more
expertise. Since most of the ocular patients in this series had
abnormal SFEMG either tested in the EDC or OO muscle, this test
may not be helpful in predicting the risk of progression to general-
ized MG as shown in a previous study (Weinberg et al., 1999).
The proportion of patients with positive AChRAb of 60% in this
study was rather low as compared with the previously reported
sensitivities which ranged from 80% to 90% (Lindstrom, 1977;
Lindstrom et al., 1976; Vincent and Newsom-Davis, 1985). This
might have been due to the fact that there was a high proportion
of ocular cases (37.5%) many of whom did not have AChRAb. In a
Chinese population, also with a large proportion of ocular cases,
AChRAb was detected in 87% of the cases, but the titers considered
to be positive were P0.2 nmol/L as opposed to >0.4 nmol/L used in
this study (Chiu et al., 1987). In another report, this antibody was
detected in 80.7% of Thai patients with generalized MG which was
also slightly higher than 73% in this study (Jitpimolmard et al.,
2006). However, the number of patients was different between
the two groups (70 versus 26) and there might have been some
variations among the patients and between laboratories. The titers
of antibody varied widely within the ocular and generalized
groups. Generalized patients tended to have higher titers than
the ocular patients, but the proportion of patients with higher
and lower titers were not significantly different between the two
groups.
SFEMG findings were significantly more abnormal in general-
ized than ocular cases in both the EDC and OO muscles which cor-
related with the overall clinical severity. It was not possible to
really compare the degree of involvement of these two muscles
as only one muscle was tested in each patient. With this limitation,
this study showed that the SFEMG abnormalities in the EDC and
OO muscles in ocular patients were not significantly different sug-
gesting that either muscle may be tested in ocular MG. This also re-
flected that the disease was more widespread than was clinically
apparent. In contrast, the mean of means of MCD in OO was signif-
icantly more abnormal than that in EDC in generalized cases sug-
gesting that the OO muscle was affected to a more severe degree
than the EDC muscle. This may imply that OO is more fatigable
or more vulnerable to the disease than EDC and may be the better
muscle to be tested between the two.
SFEMG was significantly more abnormal in seropositive than
seronegative patients in both EDC and OO muscles reflecting
that the disease was more severe in the seropositive than the
seronegative MG. This finding conforms to a recent study which
showed that the SFEMG abnormality correlated with the level of
AChRAb in both the OO and EDC muscles (Farrugia et al., 2009).
However, the number of patients in each sub-group of low and high
AChRAb titers in this study was probably too small to demonstrate
a statistical association between titer and SFEMG abnormality.
Acknowledgements
We thank the doctors and neurologists from Bhumibhol Aduly-
adej Hospital who sent their patients for study and Dr. Sasivimol
Rattanasiri for her help with the statistical analysis. This study
was supported by the Research Grant, Faculty of Medicine, Rama-
thibodi Hospital, Mahidol University, Bangkok, Thailand.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.clinph.2011.02.026.
References
AAEM Quality Assurance Committee. Literature review of the usefulness of
repetitive nerve stimulation and single fiber EMG in the electrodiagnostic
evaluation of patients with suspected myasthenia gravis or Lambert-Eaton
myasthenic syndrome. Muscle Nerve 2001;24:1239–47.
Chiu HC, Vincent A, Newsom-Davis J, Hsieh KH, Hung T. Myasthenia gravis:
population differences in disease expression and acetylcholine receptor
antibody titers between Chinese and Caucasians. Neurology 1987;37:1854–7.
Evoli A, Tonali PA, Padua L, Monaco ML, Scuderi F, Batocchi AP, et al. Clinical
correlates with anti-MuSK antibodies in generalized seronegative myasthenia
gravis. Brain 2003;126:2304–11.
Farrugia ME, Jacob S, Sarrigiannis PG, Kennett RP. Correlating extent of
neuromuscular instability with acetylcholine receptor antibodies. Muscle
Nerve 2009;39:489–93.
Farrugia ME, Kennett RP, Newsom-Davis J, Hilton-Jones D, Vincent A. Single-fiber
electromyography in limb and facial muscles in muscle-specific kinase antibody
andacetylcholine receptorantibody
2006;33:568–70.
Jitpimolmard S, Taimkao S, Chotmongkol V, Sawanyawisuth K, Vincent A, Newsom-
Davis J. Acetylcholine receptor antibody in Thai generalized myasthenia gravis
patients. J Med Assoc Thai 2006;89:68–71.
Kimura J. Techniques of repetitive stimulation. In: Kimura J, editor. Electrodiagnosis
in diseases of nerve and muscle: principal and practice. 2nd ed. Philadelphia: FA
Davis Company; 1989. p. 190.
Kouyoumdjian JA, Stalberg EV. Reference jitter values for concentric needle
electrodes in voluntarily activated
orbicularis oculi muscles. Muscle Nerve 2008;37:694–9.
Kuwabara S, Nemoto Y, Misawa S, Takahashi H, Kawaguchi N, Hattori T. Anti-MuSK-
positive myasthenia gravis: neuromuscular transmission failure in facial and
limb muscles. Acta Neurol Scand 2007;115:126–8.
Lindstrom J. An assay for antibodies to human acetylcholine receptor in serum from
patients with myasthenia gravis. Clin Immunol Immunopathol 1977;7:36–43.
Lindstrom JM, Seybold ME, Lennon VA, Whittingham S, Duane DD. Antibody to
acetylcholine receptor in myasthenia gravis. Prevalence, clinical correlates, and
diagnostic value. Neurology 1976;26:1054–9.
Meriggioli MN, Sanders DB. Advances in the diagnosis of neuromuscular junction
disorders. Am J Phys Med Rehabil 2005;84:627–38.
Nemoto Y, Kuwabara S, Misawa S, Kawaguchi N, Hattori T, Takamori M, et al.
Patterns and severity of neuromuscular transmission failure in seronegative
myasthenia gravis. J Neurol Neurosurg Psychiatry 2005;76:714–8.
Oh SJ. Muscle-specific receptor tyrosine kinase antibody positive myasthenia gravis
current status. J Clin Neurol 2009;5:53–64.
Oh SJ, Hatanaka Y, Hemmi S, Young AM, Scheufele ML, Nations SP, et al. Repetitive
nerve stimulation of facial muscles in MuSK antibody-positive myasthenia
gravis. Muscle Nerve 2006;33:500–4.
Pasnoor M, Wolfe GI, Nations S, Trivedi J, Barohn RJ, Herbelin L, et al. Clinical
findings in MuSK-antibody positive myasthenia gravis: a US experience. Muscle
Nerve 2010;41:370–4.
SandersDB,StalbergEV.AAEM
electromyography. Muscle Nerve 1996;19:1069–83.
Stickler DE, Massey JM, Sanders DB. MuSK-antibody positive myasthenia gravis:
clinical and electrodiagnostic patterns. Clin Neurophysiol 2005;116:2065–8.
Vincent A, Newsom-Davis J. Acetylcholine receptor antibody as a diagnostic test for
myasthenia gravis: results in 153 validated cases and 2967 diagnostic assays. J
Neurol Neurosurg Psychiatry 1985;48:1246–52.
Weinberg DH, Rizzo 3rd JF, Hayes MT, Kneeland MD, Kelly Jr JJ. Ocular myasthenia
gravis: predictive value of single-fiber electromyography. Muscle Nerve
1999;22:1222–7.
myastheniagravis.Muscle Nerve
extensordigitorumcommunis and
minimonograph#25: single-fiber
R. Witoonpanich et al./Clinical Neurophysiology 122 (2011) 1873–1877
1877