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MOTOR NERVE CONDUCTION STUDY AND MUSCLE STRENGTH IN
NEWLY DIAGNOSED POEMS SYNDROME
MINGSHENG LIU, MD,
1
ZHANGYU ZOU, MD,
1
YUZHOU GUAN, MD,
1
JIAN LI, MD,
2
DAOBIN ZHOU, MD,
2
and LIYING CUI, MD
1
1
Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 100730 Beijing, China
2
Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
Accepted 13 April 2014
ABSTRACT: Introduction: Mixed demyelination and axonal loss
are electrophysiological features of polyneuropathy, organome-
galy, endocrinopathy, M-protein, and skin changes (POEMS)
syndrome. It is unclear whether the demyelination and axonal
loss occur concurrently. Methods: Electromyography was per-
formed in 37 patients with newly diagnosed POEMS syndrome.
Compound muscle action potential (CMAP) amplitude, distal
motor latency, motor conduction velocity (MCV), and spontane-
ous activity were collected. Muscle strength was measured
according to the Medical Research Council (MRC) scale.
Results: MCV decreased in all nerves with decreased CMAP
amplitude and in 93% of nerves with normal amplitude. CMAP
amplitude decreased in 54% of nerves with decreased MCV
and was normal in all nerves with normal MCV. MCV deceased
in 95% of nerves with normal MRC. Abnormal spontaneous
activity was detected in 32% of upper limb muscles.
Conclusions: Demyelination may be the main manifestation in
POEMS neuropathy at an early stage, and axonal loss may be
secondary to demyelination as the disease progresses.
Muscle Nerve 51: 19–23, 2015
Polyneuropathy, organomegaly, endocrinopathy,
M-protein, and skin changes (POEMS) syndrome
is a rare paraneoplastic syndrome secondary to
plasma cell dyscrasia. Peripheral neuropathy is usu-
ally the dominant symptom of POEMS syndrome.
The most common initial symptoms that bring
patients to medical attention consist of numbness
and/or weakness of limbs due to peripheral neu-
ropathy (41%), peripheral edema (27%), and skin
changes (15%).
1
The neuropathy often begins in
the feet with sensory symptoms, followed by motor
symptoms, which progress in a length-dependent
fashion.
2
It is important to diagnose as early as
possible to institute treatment and obtain a better
prognosis. Nerve conduction studies (NCS) and
electromyography (EMG) are helpful for detecting
subclinical peripheral nerve damage.
Electrophysiological features of POEMS neu-
ropathy are characterized by slowing of motor con-
duction velocity (MCV) that is more predominant
in intermediate than in distal nerve segments, rare
conduction block, more severe attenuation of com-
pound muscle action potentials (CMAPs) in the
lower than the upper limbs, and more fibrillation
potentials in distal muscles in a length-dependent
pattern.
3–6
The proximal demyelinating and distal
axonal loss is supported by the pathological fea-
tures reported in POEMS syndrome.
7
The mecha-
nisms of this pattern of NCS/EMG are unclear.
Scarlato and colleagues proposed this may be due
to endothelial injury, indirectly or directly caused
by abnormal activation of endothelial cells by vas-
cular endothelial growth factor, which is overex-
pressed in the nerves of POEMS syndrome
patients.
8
Although mixed demyelination and axonal loss
have been detected in NCS/EMG or pathological
studies, it is unclear whether the demyelination
and axonal loss occur concurrently or sequentially.
At our clinical research center for POEMS syn-
drome, we investigated the changes of motor NCS
and muscle strength in patients with newly diag-
nosed POEMS syndrome to clarify the disease pro-
cess in electrophysiological studies.
METHODS
Patients. Thirty-seven consecutive patients with
newly diagnosed POEMS syndrome, all of whom
met the diagnostic criteria proposed by Dispenzieri
et al.,
9
were referred to Peking Union Medical Col-
lege Hospital from January 2009 to November
2012. None of the patients had received immuno-
therapy or other treatment before NCS/EMG stud-
ies. Thirty-four patients received high-dose
melphalan with peripheral blood stem cell trans-
plantation or melphalan plus dexamethasone after
NCS/EMG.
10
Three patients were treated with no
medications after diagnosis for special reasons,
which gave us the chance to follow-up the natural
history of the NCS/EMG changes in the disease.
NCS/EMG were performed once in 34 patients,
twice in 2 patients, and 3 times in 1 patient before
immunotherapy or other treatment. All patients
gave written informed consent according to the
study protocol, which was approved by the institu-
tional review board of the Peking Union Medical
College Hospital and in accordance with the Decla-
ration of Helsinki.
Abbreviations: CMAP, compound muscle action potential; DML, distal
motor latency; EMG, electromyography; MCV, motor conduction velocity;
MRC, Medical Research Council; NCS, nerve conduction study; POEMS,
polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes;
SA, spontaneous activity
Key words: axonal loss; demyelination; motor nerve conduction study;
muscle strength; POEMS syndrome
Correspondence to: L. Cui; e-mail: pumchcuily@yahoo.com
V
C2014 Wiley Periodicals, Inc.
Published online 18 April 2014 in Wiley Online Library (wileyonlinelibrary.com).
DOI 10.1002/mus.24267
Motor NCS in POEMS MUSCLE & NERVE January 2015 19
Electrophysiology. NCS/EMG were performed
with a Dantec Keypoint EMG machine. Ortho-
dromic sensory NCS were performed on median,
ulnar, and medial plantar nerves.
11
Conventional
needle EMG was performed in the abductor polli-
cis brevis, abductor digiti minimi, and anterior tib-
ial muscles. Room temperature was maintained to
ensure that the skin temperature remained at
>31C.
Motor NCS were performed in all subjects on
the median, ulnar, fibular, and tibial nerves with
percutaneous supramaximal nerve stimulation
while recording the CMAPs with 10-mm disk elec-
trodes. Bilateral nerves were studied in some cases,
with the patient’s permission. The median nerve
was stimulated at the wrist, elbow, and axilla, with
recording from the abductor pollicis brevis; the
ulnar nerve was stimulated at the wrist, distal
elbow, proximal elbow, and axilla, with recording
from the abductor digiti minimi; the fibular nerve
was stimulated at the ankle and below and above
the fibular head, with recording from the extensor
digitorum brevis; and the tibial nerve was stimu-
lated at the ankle and popliteal fossa, with record-
ing from the abductor hallucis. Measurement
included distal motor latency (DML), MCV, CMAP
amplitude (baseline to negative peak), area, and
duration of negative wave.
The inching technique (short-segment motor
NCS) of median (only elbow-to-axilla segment
studied) and ulnar nerves was performed on those
standard segments with partial conduction block.
The nerve was stimulated along the course of the
nerve in 2-cm increments, while recording over
abductor pollicis brevis for median nerve and
abductor digiti minimi for ulnar nerve. Measure-
ments included amplitude (baseline to negative
peak), area, and duration of negative peaks.
The diagnosis of conduction block and proba-
ble conduction block for standard and short seg-
ments of a nerve were made according to the
criteria proposed by the American Association of
Neuromuscular and Electrodiagnostic Medicine.
12
To include only true conduction block, distal
CMAP had to be 1mV.
Muscle Strength. Strength of abductor pollicis bre-
vis, abductor digiti minimi, flexor hallucis brevis,
and extensor digitorum brevis muscles was assessed
according to the Medical Research Council (MRC)
scale.
Statistical Analyses. Descriptive summaries are
presented as mean 6standard deviation (SD) for
continuous variables with a normal distribution,
median (P
25
–P
75
) for continuous variables with
non-normal distributions, or as proportions for cat-
egorical variables. The chi-square test was used for
2-group comparisons of categorical variables. The
independent-samples t-test was used for 2-group
comparisons of continuous variables with normal
distributions. Differences in CMAP amplitude
between different groups were analyzed by Mann–
Whitney U-test. All tests were 2-sided with P0.05
considered significant.
RESULTS
Clinical Features. There were 23 men and 14
women assessed. The mean age at onset was
47.5 69.8 years (range 29–70 years), median (P
25
–
P
50
) duration of illness was 12.0 (8.0–30.0)
months, and median (P
25
–P
50
) duration from
onset of neurological symptom to diagnosis was
10.0 (6.0–12.0) months. Peripheral neuropathy was
the initial symptom in 24 patients. The types of M
protein consisted of IgA-kin 25 patients, IgG-kin
9, and kalone in 3.
Electrophysiology. A total of 192 nerves were eval-
uated. MCV, CMAP amplitude, DML, and muscle
strength of different nerves are summarized in
Table 1. MCV, CMAP amplitude, and MRC were
significantly decreased in nerves of the lower limbs
compared with the upper limbs (P<0.01); there
was no difference between median and ulnar
nerves in MCV, CMAP amplitude, and MRC
(P>0.05), with the same between tibial and fibular
nerves. No CMAP was evoked in 8 upper limb
nerves in 4 patients, CMAP amplitude was <1mV
in 8 upper limb nerves of 2 patients, and MCV of
the 8 nerves ranged from 14.4 to 32.5 m/s. No
CMAP response was evoked in almost half of the
lower limb nerves, which was significantly higher
than in upper limb nerves (P<0.01). The DML
was delayed more severely in median than ulnar
nerves (P<0.01), and was more severe in tibial
nerve than fibular nerve (P<0.01), possibly due to
pressure on the median nerve at the wrist (carpal
tunnel syndrome) and the tibial nerve at the ankle
(tarsal tunnel syndrome).
MCVs were measured in 139 nerves. MCVs were
decreased in all nerves with decreased CMAP
Table 1 . Motor NCS results of different nerves in POEMS
syndrome.
Median Ulnar Tibial Fibular
n/N 55/58 53/58 19/38 18/38
Amplitude
(mV)
5.3 (2.5,7.7) 5.1 (2.5,6.7) 0.1 (0,0.4) 0 (0,0.4)
DML (ms) 5.5 63.0 3.961.5 7.6 62.9 5.8 61.9
MCV (m/s) 33.4 69.4 35.9 69.2 25.1 64.8 25.4 65.3
MRC score 5.0 (4.8,5.0) 5.0 (4.0,5.0) 3.0 (0,4.0) 2.0 (0,4.0)
n/N are given for the number of nerves evoked CMAP response out of
all nerves studied. Median and (P
25
,P
75
) data are given for MRC score
and amplitude. Data are expressed as mean 6SD for MCV and DML.
20 Motor NCS in POEMS MUSCLE & NERVE January 2015
amplitude and 93% of nerves with normal ampli-
tude. CMAP amplitude was decreased in 54% of
nerves with decreased MCV and was normal in all
nerves with normal MCV (Table 2). MCV was
decreased in 89 of 94 nerves with normal MRC
score and in all nerves with decreased MRC score.
CMAP amplitude was decreased in 67% of nerves
with normal MRC score and in 96% of nerves with
decreased MRC score. DML was normal in 41 of
94 nerves with normal MRC score and was delayed
in 42 of 51 nerves with decreased MRC score. Fig-
ure 1 shows the correlation between MCV, CMAP
amplitude, DML, and muscle strength of all nerves
with recordable CMAPs. Figure 2 shows MCV,
CMAP amplitude, and DML changes at different
MRC scores of the ulnar nerve as an example.
Abnormal spontaneous activity (SA) was
detected in 32% of upper limb muscles and in
95% of lower limb muscles. Sensory nerve action
potentials could not be elicited in 11% (12 of 108)
of upper limb nerves and 68% (52 of 76) of lower
limb nerves. Sensory nerve conduction velocity was
decreased in all nerves.
Partial motor conduction block was detected in
18 of 192 nerves, whereas the corresponding mus-
cle strength was normal in 12 nerves, grade 4/5 in
3, and grade 3/5 in 3. The inching technique was
performed on those nerves with conduction block
across standard segments. It showed that the
amplitude decreased gradually but not abruptly
along those nerves, and thus no conduction block
was detected.
Follow-up NCS/EMG data were obtained in 3
patients. All showed that decreased MCV was the
earliest manifestation in motor NCS. The changes
in MCV, CMAP amplitude, DML, MRC, and SA in
1 patient during a relentless progression of the dis-
ease are presented in Table 3.
DISCUSSION
In this study, NCS/EMG showed mixed demye-
lination and axonal loss in all patients with newly
diagnosed POEMS syndrome, as reported previ-
ously. A prominent feature of POEMS neuropathy
was markedly attenuated or absent CMAPs, abun-
dant SA, and decreased MRC score in lower limbs,
even when the CMAP amplitude and MRC score in
upper limbs were normal. These features indicate
Table 2. Proportions of abnormal CMAP amplitude, MCV, and
MRC score in POEMS syndrome.
MCV MRC score
Abnormal Normal Abnormal Normal
Abnormal amplitude 72 0 94 63
Normal amplitude 62 5 4 31
FIGURE 1. Scattergrams of changes in MCV, CMAP amplitude, DML, and MRC score for all nerves with obtainable CMAPs. The 4
panels (from 1 to 4) indicate median, ulnar, tibial, and fibular nerves, respectively. Closed circles indicate a patient with corresponding
parameters. (A) MCV decreased in all nerves with decreased CMAP amplitude and in most nerves with normal amplitude. (B) CMAP
amplitude decreased even when MRC score was normal. (C) MCV decreased in almost all nerves even when MRC score was normal.
(D) DML was normal or mildly delayed in most nerves. When MCV was decreased markedly, DML was also delayed significantly.
Motor NCS in POEMS MUSCLE & NERVE January 2015 21
that involvement of motor nerves occurs earlier
and more severely in lower than upper limbs, and
it seems that the major electrophysiological mani-
festations are axonal loss in the lower limbs and
demyelination in the upper limbs. However, this
does not mean that the 2 pathological changes
occur concurrently at onset of the disease.
We found that MCV was decreased in 93% of
nerves with normal amplitude and in 95% of nerves
with normal MRC. SA was rare in muscles inner-
vated by those nerves, which indicates that
decreased MCV was the prominent manifestation.
Demyelination should be the primary pathological
change and occurred earlier than axonal loss for
those nerves in the early stages of the disease. This
phenomenon was more common in upper limbs
than lower limbs when NCS/EMG were performed.
We also found that MCV was decreased in
nerves with decreased CMAP amplitude, and SA
was detected in some muscles innervated by those
nerves. Both demyelination and axonal loss can
lead to slowing of MCV. For axonal neuropathies,
when CMAP amplitude is normal or slightly
decreased, MCV should be in the normal range
and, when CMAP amplitude is decreased signifi-
cantly, some slowing of MCV may occur but usually
never reaches the unequivocal demyelinating
range. In patients with POEMS neuropathy, how-
ever, MCV was <40 m/s in almost all nerves with
decreased CMAP amplitude, as shown in Figures 1
and 2. This indicates that the decreased MCV
should be due to demyelination or that demyelin-
ation coexisted with axonal loss, and the axonal
loss may be secondary to demyelination.
There were some nerves with no CMAP
response or CMAP amplitude <1 mV, especially in
the lower limbs. It was difficult to determine what
the pathological changes were in those nerves at
an early stage. However, when no CMAP was
evoked in lower limb nerves, the CMAPs could still
be acquired in upper limb nerves in almost all
patients, and the upper limb nerves always showed
demyelinating features. Although the pathogenesis
of POEMS neuropathy remains uncertain, it
should be the same for all nerves of an individual
patient. That is, the lower limb nerves may also
have had demyelination at an earlier stage, and
with progression of the disease the CMAP ampli-
tude and MRC of lower limb nerves was decreased.
FIGURE 2. Scattergrams of changes in MCV, CMAP amplitude, and DML at different MRC levels in the ulnar nerve. The 5 panels indi-
cate different MRC groups from grades 1–5. Closed circles indicate a patient with corresponding parameters. Dotted lines indicate the
normal limit values for parameters studied (normal limit of ulnar nerve: DML 3.3 ms; MCV 47.0 m/s; CMAP amplitude 4.9 mV). (A)
MCV decreased in all nerves with decreased CMAP amplitude and most nerves with normal amplitude. CMAP amplitude and MCV
were abnormal in most nerves with normal MRC score and in all nerves with decreased MRC score. The data show that a decrease
in MCV occurred earlier than a decrease in amplitude and MRC, and decreased CMAP amplitude occurred earlier than decrease in
MRC score. (B) MCV decreased in all nerves with abnormal DML and in most nerves with normal DML. MCV was decreased and dis-
tributed over a wide range in the MRC score 5 panel, whereas DML was delayed only slightly. Even in nerves with decreased MRC
score, the DML was only slightly delayed in most nerves. The data indicate that a delay in DML occurred later than a decrease in
MCV. DML was not a sensitive parameter for diagnosis of POEMS syndrome.
Table 3. Follow-up of NCS/EMG and MRC of a patient with
POEMS syndrome.
Nerve
Duration
(months)
MCV
(m/s)
Amplitude
(mV)
DML
(ms)
MRC
score SA
Right median 2 40.0 15.7 4.4 5 0
8 36.0 13.8 4.5 5 0
13 17.7 0.6 5.1 3 2
Right fibular 2 32.0 9.6 6.2 5 0
8 22.0 6.7 6.1 3 2
13 –* 0 –* 0 3
*Could not be obtained because no CMAP response was evoked.
22 Motor NCS in POEMS MUSCLE & NERVE January 2015
This was shown by the follow-up studies of 3 newly
diagnosed patients.
The decrease in CMAP amplitude may be due
to different mechanisms during the progression of
POEMS neuropathy. In an advanced stage, when
needle EMG demonstrated abundant SA in distal
limb muscles, the decrease in CMAP amplitude
was likely due to axonal loss. After SA occurred,
the decrease in CMAP amplitude became more sig-
nificant, consistent with decreased muscle strength.
In the early stage, when NCS/EMG showed
decreased CMAP amplitude without abnormal SA,
the decrease in CMAP amplitude was likely due to
temporal dispersion and phase cancellation from
demyelination. Conduction block can also lead to
decreased CMAP amplitude, which is detected
occasionally in POEMS syndrome,
3–6
but we
believe this may not be the mechanism for POEMS
neuropathy. First, if the decreased CMAP ampli-
tude was due to conduction block, the decreased
MRC should parallel the decrease in CMAP ampli-
tude. However, from Figures 1 and 2, we can see
that, when CMAP amplitude decreased signifi-
cantly, MRC was normal or only slightly decreased.
Second, we found that conduction blocks across
standard segments were detected in 9% of nerves.
However, inching studies showed that the ampli-
tude decreased gradually but not abruptly along
those nerves, thus the motor conduction block in
POEMS syndrome may be pseudo-conduction
block. This is consistent with reports that the
demyelination in POEMS neuropathy is uniformly
and diffusely distributed along the nerve trunk,
somewhat like that in Charcot–Marie–Tooth dis-
ease type 1 rather than chronic inflammatory
demyelinating polyneuropathy.
3,4,13,14
This study was based on patients with newly
diagnosed POEMS, which can reflect the natural
process of nerve damage. We speculate that, in the
early stage, even when there are no signs or symp-
toms of motor system disease, the MCVs may be
decreased in lower limb nerves and, with relentless
progression of the peripheral neuropathy, the
CMAP amplitude will decrease, axonal loss will
occur, and muscle strength will decrease in lower
limbs. This process may occur later in upper limbs,
or it may occur at the same time as in lower limbs,
but progress more slowly. However, this hypothesis
is based mainly on observations of consecutive
patients, because we had follow-up on only 3 cases.
We suggest that more patients be studied to obtain
more definitive evidence.
In conclusion, this study has shown that signs
of demyelination are more frequent and promi-
nent than axonal loss in POEMS neuropathy in
the early stages of the disease. Demyelination may
be the main manifestation at onset of the neuropa-
thy, and axonal loss is likely secondary to demyelin-
ation as the disease progresses. Recognition of
these features can lead to early diagnosis of
POEMS syndrome and can offer some clues for
better understanding the mechanism and patho-
physiology of POEMS neuropathy.
This study was based on a poster presented at the annual meeting
of the American Association of Neuromuscular and Electrodiag-
nostic Medicine, October 2012, Orlando, Florida, USA. The poster
was awarded the President’s Research Initiative Award.
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