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Repetitive Nerve Stimulation in Myasthenia Gravis - Relative Sensitivity of Different Muscles.
Repetitive Nerve Stimulation in Myasthenia Gravis - Relative Sensitivity of Different Muscles.
Repetitive Nerve Stimulation in Myasthenia Gravis - Relative Sensitivity of Different Muscles.
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Abstract
Objective: To correlate repetitive nerve stimulation (RNS) decrement in different muscles with the predominant clinical presentation in
myasthenia gravis (MG), and to study single fibre EMG (SFEMG) sensitivity in ocular MG.
Methods: Sixty-nine, untreated, consecutive patients suspected for MG were observed prospectively for a minimum of 6 months.
Those who improved on medical treatment were diagnosed as MG. The others, in whom the neurophysiological studies were normal and that
did not improve on medical treatment served as a control group, from which normative data for RNS and SFEMG was obtained. The MG
patients were further classified in 3 subgroups according to the predominant clinical presentation: group I (ocular); group b (bulbar);
and group a (axial). We performed RNS in nasalis, trapezius, anconeus, and abductor digiti minimi. All patients with ocular MG underwent
jitter determination of the orbicularis oculi muscle.
Results: Thirty-seven patients were diagnosed as MG (group I, 15; group b, 13; group a, 9). In group I, RNS was abnormal in 33% of the
patients. RNS studies disclosed at least one abnormal muscle response in every patient in groups a and b. Trapezius was significantly more
sensitive in group a, and anconeus and nasalis in group b P , 0:01: Jitter was abnormal in all patients in group I, and the most sensitive
parameter was an increased number of unstable pairs, 100%.
Conclusions: Based on these observations, we recommend that a shoulder muscle, as the trapezius, should be studied first in the limb-axial
presentation of MG, and the anconeus nasalis muscles in predominant bulbar MG. In ocular MG, RNS is not sensitive and jitter should be
performed in facial muscles.
Significance: This paper shows the unequal sensitivity of several muscles to RNS in different forms of MG.
q 2004 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
Keywords: Myasthenia gravis; Repetitive nerve stimulation; Single-fibre EMG; Jitter
1. Introduction and Young, 1976; Stalberg, 1980), and facial muscles are
more sensitive in ocular MG (Oey et al., 1993).
Repetitive nerve stimulation (RNS), introduced by Overall RNS is abnormal in more than 70% of patients
Harvey and Masland (1941), has become the most routinely with MG when proximal muscles are investigated (Oh et al.,
used test for the diagnosis of myasthenia gravis (MG) 1992). This value is significantly lower in patients with mild
(Keesey, 1989; Stalberg, 1980). RNS is commonly available generalized MG (Claussen et al., 1995; Stalberg and
in neurophysiology laboratories and shows a good Sanders, 1981), and in patients with ocular MG the
correlation with the clinical assessment of disease severity abnormality rate can be less than 30% of the tested subjects
(Keesey, 1989). Most often recordings are from the small (Claussen et al., 1995; Stalberg, 1980). RNS studies in
proximal muscles are more painful and more prone to
hand muscles, although proximal muscles have been shown
artefactual changes (Claussen et al., 1995; Stalberg, 1980),
to be more sensitive than distal ones (Claussen et al., 1995;
but stimulation of the upper trapezius or anconeus muscles
Kennett and Fawcett, 1993; Krarup, 1977; Ozdemir
are better tolerated than stimulation of other proximal
* Corresponding author. Tel.: 351-21-780-5219; fax: 351-21-752- muscles at Erbs point, in the axilla or in the leg (Claussen
0801. et al., 1995; Keesey, 1989; Kennett and Fawcett, 1993;
E-mail address: mamedemg@mail.telepac.pt (M. de Carvalho). Schumm and Stohr, 1984).
1388-2457/$30.00 q 2004 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.clinph.2004.05.024
J. Costa et al. / Clinical Neurophysiology 115 (2004) 27762782 2777
Ocular symptoms (fluctuating diplopia and ptosis) are the those with mild, moderate and severe disease); group a
most common presenting complaints of patients with MG. (axial, limb-girdle, including those with mild, moderate and
However, predominant bulbar features (dysphagia, dyspho- severe disease). Our classification is in agreement with the
nia, oral muscle fatigue) can occur in up to one-quarter of criteria from the Myasthenia Gravis Foundation of America
the patients with MG at onset (Emilia-Romagna Study (MGFA) (Jeretzki et al., 2000), which was published after
Group, 1998). In 15 20% of the patients the first complaint the onset of this study. There were small number of subjects
is weakness of the arm or hand muscles, or of the legs. and all of them were with mild and moderate MG. So, we
(Oosterhuis, 1997). did not subclassify them by disease severity.
No previous study tried to correlate the decrement to RNS All patients of both groups underwent routine blood tests,
in different muscles with the predominant clinical presen- thyroid function tests, thoracic CT scan, and determination
tation. Our study aimed to investigate the decrement to RNS of serum antibodies to human AchRassayed following the
of various proximal and distal muscles in patients with standard immnunoprecipitation method using purified
different presenting forms of MG (ocular, bulbar, or human Ach-R (abnormal . 0.4 nmol/l). Selected cases
axial/limb-girdle). were submitted to CT scan or MRI of the head, in particular
patients with ocular MG.
polyneuropathy. Post-exercise stimulation of the ulnar nerve These patients were diagnosed with different disorders
was done to rule-out the presence of incremental response during the follow-up: cranial nerve palsy, ocular myopathy,
(. 50% increase in area or amplitude). Post-activation congenital ptosis, blepharospasm, alternating strabismus,
exhaustion was not tested in this study. metabolic myopathy, depression and chronic fatigue
All neurophysiological studies were performed by the syndrome. Control subjects were well matched with MG
same neurophysiologist (M de C) with the same equipment patients for age (Student t-test, P . 0:05) and gender
(Keypoint, Medtronic, Skvolunde, Denmark). (x2 ; P . 0:05). From these patients we obtained our
normative material for RNS and SFEMG.
2.3. Single-fibre EMG (SFEMG)
All patients who were included with the clinical 3.1.1. RNS studies results
diagnosis of ocular MG underwent SFEMG study of the The neurophysiological results obtained in this group are
orbicularis oculi (OO), bilaterally. A standard method was summarized in Table 1.
used (Sanders and Stalberg, 1996). The SFEMG needle In all individually tested muscles, the area decrement
electrode was inserted at the edge of the muscle. The patient was significantly higher than the amplitude decrement
was asked to maintain the muscle on slight contraction.
(Student t-test, P , 0:05). Decrement of the area and
Amplifier settings were at 500 Hz 10 KHz. Single-fibre
amplitude was smaller for the ADM as compared with the
responses were selected based on short rise times
other muscles (one-way ANOVA, P , 0:05; post-hoc
(, 300 ms), clear separation from other discharges,
Tuckey test , 0.05), but no differences were found between
and stable wave forms with an amplitude above 150 mV.
anconeus, trapezius, nasalis and APB muscles P . 0:05:
The mean jitter was calculated from 20 accepted single-fibre
Decrement of the amplitude did not show normal distri-
responses (10 pairs per side), although in patients with clear
bution, but decrement of the area did (Kolmogorov
abnormalities in this test a smaller number was accepted
(minimum of 10 pairs). Smirnov, P . 0:05). For this last reason we decided to use
In a selected number of patients with generalized MG the decrement of the area for further analysis and
and abnormal decremental responses, SFEMG studies of the comparisons. Based on our results we set 7% as the upper
extensor digitorum communis was performed with the same limit for area decrement of the 4th response in all tested
method, as described elsewhere (Sonoo et al., 2001). muscles (Table 1).
Total number 32, n % Decrement % Decrement ULN for ULN for area
(F:M 18:14) of amplitude, of area, mean ^ SD amplitude decrement(%)
mean (range) (range) decrement (%)
RNS, repetitive nerve stimulation; n; number; ADM, abductor digiti minimi; APB, abductor pollicis brevis; ULN, upper limit of normal; SD, standard
deviation. The values between brackets represent the range of the results.
a
Non-normal distribution.
b
Normal distribution.
c
Taking into account that amplitude has a non-normal distribution and one control subject showed a value of 5% for the amplitude decrement in the APB, we
set as 5% the upper limit of normal.
d
The first value corresponded to mean value 3D. However, since one control subject showed a value of 7% for the area decrement in the APB we set as 7%
the upper limit of normal.
J. Costa et al. / Clinical Neurophysiology 115 (2004) 27762782 2779
Table 3
Myasthenic patientsclinical data
1 n Sex: F:M Age, mean Symptom duration, Follow-up, median Positive AchR-Ab Thymoma
(SD) range median (months) (months) range (%) (%)
range (months) (months)
Class, classification; I, ocular; b, predominant bulbar symptoms; a, axial/limb-girdle type; M, male; F, female; SD, standard deviation; AchR-Ab,
acetylcholine antibodies.
2780 J. Costa et al. / Clinical Neurophysiology 115 (2004) 27762782
(AAEM Quality of Assurance Committee 2001a,b). slightly lower than the described elsewhere (Bromberg and
In particular, this study has two important characteristics: Scott, 1994; Sanders and Stalberg, 1996).
all patients were studied before treatment and the final In one previous experience comparing the stimulation rate
diagnosis was clinical, supported by the positive serum at 2 vs. 3 Hz in 10 patients with MG we did not find any
antibodies against AchR and the treatment response. difference regarding the area/amplitude decay P , 0:05;
The main limitation of this study is the small number of but the rate of 2 Hz was better tolerated in proximal
patients included. muscles (not published), for this reason we decided to
Pseudofacilitation, an increase in amplitude on RNS due perform this study using a stimulation rate of 2 Hz. In our
to synchronization of muscle fiber conduction (Stalberg, hands, stimulus duration of 0.1 ms augments inter-trial
1980; Lo et al., 2003) was more evident in controls than in variability, for this reason we decided to use 0.2 0.3 ms
patients with MG. In our population of MG patients area stimulus duration.
decrement did not provide a higher yield than amplitude, in
opposition to the report of Lo et al. (2003).
Table 4
The control values for RNS calculated from our Diagnostic sensitivity of different muscles in groups a and b
non-myasthenic population are identical to those published
by other authors (AAEM quality assurance committee, RNSmuscle that Number of patients (%)
showed the highest
2001b; Desmedt, 1973; Oey et al., 1993; Oh et al., 1992;
area decrement
Kennett and Fawcett, 1993; Ruys-Van Oeyden and Dijk, Group a, Group b, Fishers exact
2002; Schumm and Stohr, 1984; Stalberg, 1980). We did not n 9 n 13 test (MG group
include deltoid in our protocol, although this is probably a a vs. group b)
very sensitive muscle to show abnormalities in MG
(Yiannikas et al., 1994). However, there is reduced Trapezius 8 (89%) 0 (0%) P # 0:0001
Anconeus 1 (11%) 6 (46%) P 0:09
information on this muscle in the literature (AAEM Quality Nasalis 0 (0%) 7 (54%) P # 0:01
of Assurance Committee, 2001b) and in our experience Anconeus or Nasalis 1 (11%) 13 (100%) P , 0:0001
many patients do not tolerate this investigation, as ADM 0 (0%) 0 (0%) P1
experienced by others (Claussen et al., 1995; Keesey, Note: no comparisons were made for Group I since RNS was abnormal
1989; Kennett and Fawcett, 1993; Schumm and Stohr, in only 5 of these patients (33%). Trapezius showed the highest area
1984). The jitter value of the OO in our population is decrement in 3, anconeus in 1, and nasalis in 1.
J. Costa et al. / Clinical Neurophysiology 115 (2004) 27762782 2781
In our population the sensitivity of RNS in group I was perform SFEMG of at least one symptomatic muscle.
lower than reported in some studies (Stalberg, 1980), Another recommendation (based on class C evidence) was
although similar to other reports (AAEM quality provided for patients with very mild or solely ocular
assurance committee, 2001b). We cannot discuss the role symptoms and when it is believed that RNS will be
of post-activation exhaustion upon these differences, normal, recommending SFEMG test as the initial electro-
since we did not include this technique in our study. diagnostic test.
However, SFEMG of the OO proved to be a very sensitive Although we have studied a small population of patients
technique in ocular MG, as reported before in studies with MG, our results suggest some changes to those
involving facial muscles (Stalberg, 1980; AAEM quality recommendations. These suggestions are only appropriate
assurance committee, 2001b; Oh et al., 1992; Padua et al., after excluding the diagnosis of pre-synaptic neuromuscular
2000). In our study the number of unstable pairs was the transmission defect by investigating incremental response
most sensitive index. This paper confirms that the less after muscle contraction or with high-repetitive stimulation
sensitive test for ocular MG is the presence of positive (Maddison et al., 1998). Taking into account the
AchR-Ab (Oh et al., 1992). patient tolerability, we propose that: (1) RNS of the
In our patients with generalized MG, hand muscles were trapezius (or probably another shoulder muscle) should
not as sensitive as described by others (Niks et al., 2003; Oey be performed first in patients with predominant limb-axial
et al., 1993; Ozdemir and Young, 1976; Shumm et al., 1984). fatigue; (2) anconeus and nasalis muscles should be tested
Probably, this is due to the absence of patients with severe first in patients with predominant bulbar presenting features;
disease in our population. The APB tended to be more (3) RNS of the ADM is not helpful in the electrodiagnostic
sensitive than the ADM (mean area decrement of 9.4 and 22.0 of MG, although it can be quite valuable to exclude
for the APB, as compared with 4.8 and 14.4% for the ADM, pre-synaptic transmission defect (Maddison et al., 1998);
in groups a and b, respectively). However, RNS of the (4) in patients with pure ocular MG, RNP it is not sensitive
proximal muscles proved to be a significantly more sensitive and SFEMG of the facial muscles could be tested first in
method to confirm generalised MG (AAEM quality assur- laboratories where this technique is available.
ance committee, 2001b; Desmedt, 1973; Jeretzki et al., 2000;
Kennett and Fawcett, 1993; Krarup, 1977; Ozdemir and
Young, 1976; Pavesi et al., 2001; Stalberg, 1980; Shumm, Acknowledgements
1984).
This study shows for the first time that the trapezius The authors are grateful to Ana Macedo for statistical
muscle is more sensitive in myasthenic patients presenting advice and to Professor Jose Ferro for referring some
with limb-girdle and axial weakness, and that anconeus or patients.
nasalis are more sensitive in patients presenting with
predominant bulbar features. It is well known that weakness
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