Review Article

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March 2015

Practical Rules for Electrodiagnosis in

Suspected Multifocal Motor Neuropathy
Mark B. Bromberg, MD, PhD* and Hessel Franssen, MD, PhD

Abstract
Multifocal motor neuropathy (MMN) with conduction block (CB) is a rare chronic immune-mediated
neuropathy, but important to diagnose as it is
treatable. The key features in prototypic MMN are
electrodiagnostic demonstration of focal CB away
from common sites of entrapment and normal
sensory conduction across these sites. However,
there are challenges in distinguishing CB from the
effects of abnormal temporal dispersion. Consensus electrodiagnostic criteria, reinforced by modeling studies, are available to support definite or
probable CB. In addition, consideration of technical issues can guard against false-positive and falsenegative conclusions. These include limb temperature, stimulus site, inadvertent stimulating electrode movement, and supramaximal and
submaximal responses, as well as the possibility
of Martin-Gruber anastamosis. Robust evidence
supports the treatment of MMN with intravenous
immunoglobulin, and guidelines have been developed. Application of practical and simple rules
including a 4-step diagnostic algorithm can help
practitioners correctly diagnose this treatable condition and improve patient outcomes.
Key Words: multifocal motor neuropathy, conduction block, immune-mediated neuropathy, electrodiagnosis, nerve conduction studies

( J Clin Neuromusc Dis 2015;16:141152)

INTRODUCTION
Multifocal motor neuropathy (MMN)
with conduction block (CB) is a rare form
of neuropathy but important to diagnose as it
is a treatable condition. This review considers
the clinical phenotype, the electrodiagnostic
criteria for CB, the supportive laboratory
tests, treatment, and prognosis. The clinical
features are unique and are a clue to consideration of the diagnosis. Electrodiagnostic
demonstration of focal CB away from common sites of entrapment is the defining

feature, but may be challenging to demonstrate, and these challenges will be considered in detail. There are few other laboratory
tests that can lend support to the diagnosis. A
small number of alternative disorders share
some features. There is robust evidence to
support the use of intravenous immunoglobulins (IVIG), and guidelines are presented.
MMN is a chronic disease and long-term
changes are also reviewed.

DESCRIPTION AND EPIDEMIOLOGY

MMN, in its prototypic form, is a chronic
immune-mediated neuropathy that affects
motor axons in mixed nerves. The pathophysiology is CB at focal sites away from entrapment sites. The pattern of weakness is initially
a mononeuropathy but over time becomes
mononeuritis multiplex and thus is asymmetric in distribution. Interestingly, the weakness
may not be complete within the distribution
of the affected nerve; for example, weakness
of extension of selected digits versus all digits
innervated by the radial nerve. Sites of focal
CB may be distributed along the length of the
nerve, from roots to distal segments, and an
individual nerve may have more than 1 site of
focal CB. Upper extremity nerves are involved
more frequently than lower extremity nerves.
MMN rarely affects cranial nerves. Muscle
atrophy can be less-than-expected for the
degree of weakness.1 Cramping and fasciculations are frequently noted in affected muscles.
Tendon reflexes from affected muscles are
reduced or absent but occasionally are noted
to be brisk.2
Untreated MMN involves more nerves
over time, but the rate of progression is slow,

From the *Department of

Neurology, University of Utah,
Salt Lake City, UT; and
Department of Neurology,
Neuromuscular Disease Group,
Brain Center Rudolf Magnus,
University Medical Center,
Utrecht, the Netherlands.
H. Franssen received honoraria
and travel reimbursement from
Baxter Healthcare Corporation
and grants from the Prinses
Beatrix Spierfonds and the
European Federation of
Neurological Societies.
M. B. Bromberg is a medical
advisory consultant for Baxter
Healthcare Corporation.
H. Franssen reports no conflicts
of interest.
Reprints: Mark B. Bromberg, MD,
PhD, Department of Neurology,
University of Utah, 175, North
Medical Drive, Salt Lake City, UT
84132 (e-mail: mbromberg@hsc.
utah.edu).
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Kluwer Health, Inc. All rights
reserved.

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Bromberg and Franssen

measured in years.3 The degree of muscle

atrophy, reflecting axonal loss, increases over
time. Prototypic forms show nerve conduction abnormalities of motor nerve fibers only,
but patients may describe paresthesias in the
distribution of affected nerves, and over time
sensory abnormalities may evolve, especially
in nerves with marked motor axonal loss.4
MMN does not affect patient longevity.
The epidemiology of MMN is difficult to
determine accurately as it is likely an underdiagnosed disorder. The prevalence is estimated to be ;0.6/100,000.2 Because it is
a chronic disease that does not shorten life,
the incidence is very much lower. Males are
affected more frequently than females (3:1).
The disorder primarily affects adults, age
range 3060 years, with the mean age of 40
years.2 No ethnic distribution has been noted.
No comorbidities have been recognized.

ELECTRODIAGNOSTIC STUDIES
IN MMN
Nerve conduction studies (NCS) are
important in the diagnosis of MMN to demonstrate underlying nerve pathology. The key
features in prototypic MMN are focal CB
away from common sites of entrapment and
normal sensory conduction across these sites.
However, the certainty whether there is CB
in a nerve or not varies and can be graded by
consensus criteria into definite and probable
CB (Fig. 1A1, A2), because frequently there
are associated demyelinating features with
slow motor conduction and abnormal temporal dispersion (Fig. 1A3). These 2 factors (fibers with CB and fibers with slowing)
represent the challenges in determining CB.
There is no such thing as degree of CB; 1
axon has either CB or no CB. Only the number of axons with CB can vary in a nerve, but
this cannot be estimated by NCS. Furthermore, the number of affected nerves varies
from 1 or more. This leads to classification for
a patient as having definite or probable MMN.
From clinical experience, patients with clinical features of MMN will respond to IVIG
treatment in 81% if definite CB is found in

at least 1 nerve, in 71% if only probable CB

is found, and in 11% if no CB is found and
only demyelinative motor conduction slowing.3 Thus, probable CB or slowing can be
the only finding in MMN and does not negate
the diagnosis.
Focal CB can be identified by showing
a compound muscle action potential (CMAP)
drop across the site of block: the CMAP after
stimulation proximal to the site of block is
smaller than the CMAP after stimulation distal
to the site of block (Fig. 1). NCS can demonstrate the location of CB and show that it is
away from common sites of entrapment. Needle electromyography (EMG) of affected
muscles neither define the pathology as CB
nor determine the location of block along the
nerve. Needle EMG can verify that there is
associated axonal loss, which occurs frequently but less often than expected for the
degree of weakness. Both weakness with atrophy and weakness without atrophy are therefore compatible with MMN. In typical MMN,
sensory nerve conduction across the site of
motor CB is normal, but during the course of
the disease some patients develop decreased
sensory nerve action potential amplitudes,
especially in mixed nerves with prominent
motor CB or motor axonal loss.4 The finding
of CB in MMN may suggest that CB is the cause
of weakness in MMN. However, a crosssectional study showed that axonal loss as detected by needle EMG, and not CB, was the
single determinant of weakness, thus emphasizing the importance of axonal degeneration.5

CRITERIA FOR CB
Although CB is straightforward to
define (cessation of impulse propagation at
a given site of a nondegenerating axon),
verifying that a drop in CMAP size between
a distal and a more proximal stimulation site
is because of CB is challenging. This is
because sufficient motor axons have to be
blocked to result in a CMAP drop, and a CMAP
drop can be caused by CB and by abnormal
temporal dispersion. Abnormal temporal dispersion is an excessive difference in slowing

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Electrodiagnostic Rules in Suspected MMN

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FIGURE 1. Motor NCS in the radial nerve with stimulation at the elbow (A1), axilla (A2), and Erb
point (A3). Elbowaxilla segment: CMAP area drop 52%; CMAP amplitude drop 56%; CMAP
duration prolongation 10%; these findings are consistent with definite CB without increased temporal dispersion. AxillaErb segment: CMAP area drop 12%; CMAP amplitude drop 54%; CMAP
duration prolongation 61%; these findings are consistent with increased temporal dispersion without
CB. CMAP drop was calculated as: [(distal CMAP size) 2 (proximal CMAP size)] 3 100%/[distal
CMAP size]. Duration prolongation was calculated as: [(proximal CMAP duration) 2 (distal CMAP
duration)] 3 100%/[distal CMAP duration]. MCV upper arm 41 m/s and MCV shoulder 23 m/s.

between individual motor axons within

a nerve and usually reflects altered or damaged myelin. In MMN, both focal CB and focal
increased temporal dispersion frequently
occur together. Therefore, diagnostic criteria
are necessary to distinguish CMAP changes
due to CB and abnormal temporal dispersion.
The CMAP is the sum of individual motor
unit potentials (MUPs) as recorded by surface
electrodes over the muscle evoked by supramaximal stimulus to the nerve. Each surfacerecorded MUP has an initial negative and
following positive phase (Fig. 2). In normal
nerve, conduction velocities in individual myelinated axons range from 55 to 40 m/s. Lategenerated MUPs have their negative portions
shifted temporally over positive portions of
early generated MUPs, and the CMAP waveform will reflect the algebraic summation that
includes phase cancellation. Thus, CMAP
waveforms from more proximal stimulation
sites will be of lower amplitude and area
because of the spreading out (desynchronization) of individual MUPs. Note that there is
a greater effect of phase cancellation on the
metric of CMAP amplitude than on area, and

the latter is the preferred metric to focus on

when assessing for CB. The degree of temporal
dispersion is expressed by comparing the negative peak duration of the CMAP on proximal
stimulation with that on distal stimulation
(CMAP duration prolongation). In normal
median and ulnar nerves, CMAP drop between
wrist and shoulder segments was up to 21% for
amplitude and 19% for area and CMAP duration prolongation up to 11% (Fig. 3).
In a nerve affected by demyelination,
the main pathophysiologic changes are CB,
slowing, or both. Pure CB leads to a CMAP
drop without abnormal duration prolongation
on more proximal stimulation (Fig. 4). Pure
slowing may cause some individual MUPs to
be conducted later than usual (desynchronization). Because of desynchronization, the
CMAP on more proximal stimulation will be
lower and broader (duration prolongation).
Desynchronization also causes greater than
normal phase cancellation between the positive and negative phases of the MUPs contributing to the CMAP; this gives rise to an
additional CMAP drop. An abnormally large
CMAP duration prolongation because of
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FIGURE 2. Model of the effects of normal and abnormal temporal dispersion on the CMAP. Top
portion: Fastest and slowest single MUPs conducting at normal velocities resulting in minimal degree
of phase cancellation. Lower portion: Slowest single MUP conducting at slower than normal
velocities resulting in abnormal degree of phase cancellation and lower CMAP.

desynchronization is known as increased

(abnormal) temporal dispersion. Because in
MMN both focal CB and abnormal temporal
dispersion frequently occur in the same nerve,
there are 2 different levels of diagnostic certainty (Table 1).6,7 Definite CB denotes that
the CMAP drop is sufficiently large to prove
CB and is not, or is little, associated with signs
of increased temporal dispersion. Probable
CB refers either to a CMAP drop that is larger
than normal but not sufficiently large to prove
CB, or to a CMAP drop associated with signs
of increased temporal dispersion.

The maximal effects of CB and abnormal temporal dispersion were modeled using
surface recorded single MUPs obtained from
animals or human nerves.8,9 CMAPs were
reconstructed by varying the number of
blocked MUPs or varying their degree of synchronization, thus simulating a wide range of
different degrees of CB and temporal dispersion (Table 2). Pertinent results from these
studies include the following. First, temporal
dispersion affects CMAP amplitude to a far
greater extent than CMAP area: extreme temporal dispersion caused a CMAP drop for

FIGURE 3. Effects of normal temporal dispersion on the CMAP stimulating from wrist (A1) to Erb
point (A5). MCV wrist to below elbow 63 m/s; MCV across elbow 67 m/s; MCV above elbow to axilla
69 m/s; MCV axilla to Erb point 65 m/s.
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Electrodiagnostic Rules in Suspected MMN

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FIGURE 4. Model of the effects of CB and abnormal temporal dispersion of the resultant CMAP. Top
left: Effects of normal temporal dispersion on CMAP. Top right: Effects of pure CB. Bottom right:
Effects of abnormal temporal dispersion and no CB.

amplitude of up to 80% but for area not

exceeding 50%. Therefore, a CMAP area drop
of more than 50% denotes CB, regardless of
the amount of temporal dispersion. Second,
for CMAPs recorded from hand muscles, CB
criteria were defined for different amounts of
temporal dispersion and distal CMAP duration.
Third, blocking the fastest conducting fibers
results in the greatest degree of CB; however,
there are no data on whether fast conduction
fibers are preferentially affected in MMN.8
Fourth, with extreme temporal dispersion
the above-described desynchronization is such
that MUPs are generated after 1 another and
phase cancellation does not occur. This phenomenon limits the effect on CMAP area drop
that can be attributed to abnormal temporal
dispersion; greater reductions in CMAP area
can thus be attributed to CB.
It is probably not meaningful to demonstrate focal CB when the distal CMAP

amplitude is ,1 mV. This is because (1) the

effects of normal temporal dispersion
become more apparent when there are few
remaining fibers so that a CMAP drop is erroneously attributed to CB and (2) IVIG has not
been shown to be beneficial in patients in
whom the only manifestation of CB occurs
in nerves with a distal CMAP below 1 mV.6
Based on the above, an algorithm can
be applied for MMN diagnosis by CB that
compares the negative parts of the distal and
proximal CMAP (Fig. 5).
Alternatively, consensus criteria have
been set forth that formulate detailed limits
for the amount of CMAP drop and CMAP
duration prolongation that have to be fulfilled
for definite or probable CB (Table 1).6,7 These
criteria are, however, insufficiently based on
evidence, are unnecessarily complicated, and
were shown to result in underdiagnosis of
MMN.10

TABLE 1. AA(N)EM Criteria for CB Based on Expert Opinion

Definite CB
Probable CB
Possible CB

CMAP Segment
Amplitude Reduction

CMAP Segment Area

Reduction

CMAP Negative Peak Duration

Segment Increase

.50%
.40%
.50%

.40%
.30%
.40%

,30%
,30%
31%60%

AA(N)EM, American Association of Neuromuscular and Electrodiagnostic Medicine.

Adapted with permission from Ref. 7. Adaptations are themselves works protected by copyright. So in order to
publish this adaptation, authorization must be obtained both from the owner of the copyright in the original work and
from the owner of copyright in the translation or adaptation.
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TABLE 2. Cutoff Criteria for CB for Median or Ulnar Nerve Motor Conduction Studies With
Recording From Hand Muscle
Distal CMAP Duration
,9 ms
CMAP Duration Prolongation in ms
0
01
13
35
58

912 ms

.12 ms

Segmental CMAP Area Reduction, %

25
35
45
55
60

25
35
40
45
50

25
30
40
40
45

Data are based on reconstruction of CMAPs from human surface MUPs of hand muscles and apply to forearm,
upper arm, and shoulder segments. Duration prolongation refers to increase in ms (not in %) of CMAP duration on
proximal versus distal stimulation across the segment. Distal duration refers to CMAP duration in ms on distal
stimulation of the segment. Segmental CMAP area reduction refers to [(area on distal stimulation) 2 (area on proximal
stimulation)] 3 100%/[area on distal stimulation]. Area refers to the area of the negative phase or total area of all
negative phases in case of polyphasic CMAP. Adapted with permission from Van Asseldonk JTH, Van den Berg LH,
Wieneke GH, et al. Criteria for conduction block based on computer simulation studies of nerve conduction with
human data obtained in the forearm segment of the median nerve. Brain. 2006;129:24472460. Adaptations are
themselves works protected by copyright. So in order to publish this adaptation, authorization must be obtained
both from the owner of the copyright in the original work and from the owner of copyright in the translation or
adaptation.

LOCATION OF CB IN MMN
CB was found most frequently in upper
limb nerves in 1 study,11 but in another study
it was equally distributed between upper and
lower limb nerves.12 The ulnar and median
nerves are similarly affected. Note that CB
can also be demonstrated in more proximal
upper limb nerves, including the radial and
musculocutaneous nerves. The greatest challenge is demonstrating CB in nerve segments
in the brachial plexus and roots, especially
when block is not demonstrated in distal segments and proximal block is being relied
upon for the diagnosis.
Stimulation at Erb point and at the root
level may not be supramaximal because of
limits of stimulator current output from the
EMG machine if there is a large amount of
tissue between the stimulating electrode and
the nerve. Magnetic stimulation is not readily
available and may not result in supramaximal
activation. Needle stimulation of roots also
may not result in supramaximal stimulation.
In lower limb nerves, CB can be demonstrated in the peroneal (fibular) nerve in

segments between the fibular head and the

ankle. However, caution is warranted with the
tibial nerve as there is frequently a large CMAP
area or amplitude drop to stimulation at the
popliteal fossa due either to submaximal
stimulating current or the effects of volume
conduction recorded from the reference electrode when activating proximal muscles by
stimulating at the popliteal fossa.13

PRACTICAL ISSUES IN
CB DETERMINATION
A number of nerve conduction techniques and technical issues should be considered
to help guard against false-positive and falsenegative conclusions about CB.

Limb Temperature
Nerve temperature is important as CB
may be missed at low temperature and optimized at high temperature.14,15 Temperatures
should be 37C, and correction factors for conduction velocity should not be used. To ensure
such a temperature, a limb should be immersed
in a warm water bath for 30 minutes.16

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FIGURE 5. Algorithm for diagnosing MMN by CB.

Stimulus Site
Optimization of the stimulation site can
be achieved by using submaximal current to
explore the most sensitive stimulation site,
much like finding the motor point in a muscle
(Fig. 6). The site that provides the highest
CMAP amplitude should be used for stimulation to achieve a supramaximal response.

and the shape of the holder invites stabilization (Fig. 7). Prong stimulators are frequently
held in place without stabilization and can easily slide off of the optimum site, or the level of
skin depression can lessen when the operator
is busy adjusting EMG machine controls, especially at proximal stimulation sites.

Supramaximal Response
Inadvertent Stimulating
Electrode Movement
Once the optimum site has been found,
the stimulator should remain fixed in place
while a maximal response is elicited. Use of
a felt pad stimulator has advantages over
a prong stimulator as it does not slide easily

A maximal CMAP can be ensured by

further increasing the stimulation intensity
and by an additional 20%30% after the maximal response has been achieved. When
achieving a supramaximal response, observation of the CMAP waveform is important,
especially at proximal stimulation sites,
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FIGURE 6. Optimal positioning of stimulating electrode. Left: Ultrasound scan showing position of
the median nerve and how small mediallateral movements affect optimal positioning. Center:
Stimulating electrode over wrist. Right: Effects on CMAP amplitude with slight movements of the
stimulating electrode. Left image: Reprinted with permission from JNSPG from Koenig RW, Pedro
PG, Heinen CP, et al. Neurosurg Focus. 2009;26(2):E13. Center and right images: M. B. Bromberg.
Adaptations are themselves works protected by copyright. So in order to publish this adaptation,
authorization must be obtained both from the owner of the copyright in the original work and from
the owner of copyright in the translation or adaptation.

because other motor nerves in close proximity may be inadvertently activated. This is
especially a factor when stimulating the
median nerve in the arm because proximally
the ulnar nerve is close by and can contribute
to the thenar CMAP obscuring a reduced
response due to CB.

Martin-Gruber Anastomosis
Martin-Gruber anastomosis type 1 results
in a CMAP drop between wrist and elbow
when the ulnar nerve is investigated with
recording from the abductor digiti minimi
muscle. To distinguish true CB from an anastomosis, the median nerve should be stimulated
at the elbow, while the recording electrodes
remain on the abductor digiti minimi muscle. If
an anastomosis is present, a small CMAP of

normal shape (with initial negative deflection)

will appear; this is generated by the muscle
fibers of the abductor digiti minimi innervated
by the median nerve. If there is no anastomosis
and true CB, a small broad CMAP with initial
positive deflection appears, which is generated
by thenar muscle fibers innervated by the
median nerve. This type of anastomosis was
found in both anatomic and electrophysiologic
studies in 7%30% of subjects.17

OTHER METHODS
Magnetic Resonance Imaging
Although proximal CB can be difficult
to demonstrate by nerve conduction tests,
magnetic resonance imaging (MRI) can demonstrate nerve abnormalities that, in the

FIGURE 7. Photographs showing advantages of felt pad stimulators over prong stimulators for
positioning and maintaining position at proximal stimulation sites.
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Electrodiagnostic Rules in Suspected MMN

appropriate clinical context, are supportive

of proximal pathology. MRI of nerve roots
and the plexus, or MR neurography, can
show signal hyperintensity in roots and nerve
segments indicating increased water content,
or enlarged nerves.18 Although not indicating
a specific pathological process, such as CB or
demyelination, it can be supportive, especially in patients with equivocal electrodiagnostic studies. Furthermore, MRI is readily
available and the findings of increased signal
intensity are easily detected. MRI of muscle
can also show signal changes that can localize
involved muscles and segments of muscle.18

Nerve Ultrasound
Ultrasound can be used to demonstrate
nerve pathology in MMN in the form of
enlarged nerves.19 Such findings are also not
specific but can be supportive. Ultrasound is
becoming more available but requires considerable operator experience, especially at proximal sites.20

Needle EMG
Although CB is the distinguishing feature of MMN, motor NCS may reveal reduced
distal CMAP amplitudes consistent with axonal loss. Needle EMG, even in muscles with
normal CMAP size, may show abnormal
spontaneous activity and neurogenic MUPs
in weak muscles.21 Abnormal spontaneous
activity includes fibrillation and fasciculation
potentials. Motor unit recruitment is reduced
but does not discriminate between the effects
of blocked axons and the need to recruit remaining axons at a more rapid rate and similar effects due to axonal loss. Similarly, MUP
amplitude may be increased from either the
need to recruit from large motor units in the
remaining pool or due to collateral sprouting.
Axonal loss increases over time (months to
years) in both untreated and treated patients.
The slow progression of axonal loss results in
motor units that may not have markedly complex waveforms.

Laboratory Tests
MMN is associated in approximately
50% of patients with high-titer antibodies to

ganglioside GM1, which is expressed on the

perinodal Schwann cell surface and nodal
axolemma. Low titers were also reported in
amyotrophic lateral sclerosis (ALS) and progressive muscular atrophy (PMA), but high
titers were shown to be specific for MMN if
appropriate criteria are applied.2

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DIFFERENTIAL DIAGNOSIS
There are other diagnostic considerations when thinking about MMN, and MMN is
a differential diagnosis for ALS (Table 3).
The LewisSumner syndrome, also called
multifocal acquired demyelinating sensory and
motor neuropathy, shares features with MMN
with asymmetric weakness and electrodiagnostic CB but also includes sensory deficits and
pain in the distribution of the weakness.22,23
Careful testing may show sensory CB in nerve
segments with motor CB. It should be emphasized, however, that demonstration of sensory
CB is challenging as sensory responses normally decrease on more proximal stimulation.
Comparison with the corresponding nerve on
the healthy side may reveal if the sensory
response drop on the affected side is abnormal. Distinction with MMN is important as corticosteroids are beneficial in LewisSumner
syndrome but may worsen MMN.
When there is a marked degree of
abnormal temporal dispersion and there is
a progressive reduction of the CMAP amplitude
and area with serial proximal conduction segments, consideration should be given to
chronic inflammatory demyelinating polyradiculoneuropathy.24 Although chronic inflammatory demyelinating polyradiculoneuropathy
most commonly has a symmetric distribution
of weakness and sensory disturbance, there are
primarily motor forms and asymmetric forms.25
Similarities between MMN and ALS
include asymmetric pattern of atrophic weakness, cramps, and fasciculations, and with no
sensory symptoms or signs.26 However, classical ALS involves signs of both lower and upper
motor neuron loss, and the latter is detected
by pathological reflexes. Occasionally, brisk
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TABLE 3. Differential diagnosis of MMN

LewisSumner syndrome or MADSAM
Similar electrodiagnostic findings of motor CB but includes sensory nerve involvement
Chronic inflammatory demyelinating polyradiculoneuropathy
Usually symmetric nerve involvement but may be asymmetric; usually marked degree of abnormal
temporal dispersion and slowed conduction velocities in most nerves
Hereditary neuropathy with liability to pressure palsies
CB at sites of entrapment; slowing of distal motor latencies and distal sensory nerve conduction
Vasculitis mononeuropathy multiplex
Usually painful nerve infarcts and includes sensory loss; NCS shows multifocal or asymmetric CMAP
and SNAP amplitude reductions
ALS
Usually asymmetric but more diffuse distribution of atrophy and weakness, tendon reflexes brisk;
relatively rapid progression
PMA
Usually asymmetric but more diffuse distribution of atrophy and weakness; relatively rapid progression
Inclusion body myositis
Usually asymmetric atrophy and weakness in unique distribution; very slow progression
MADSAM multifocal acquired demyelinating sensory and motor neuropathy; SNAP sensory nerve action
potential.

reflexes are noted with MMN. The entity of

PMA includes asymmetric atrophy weakness
with normal or reduced reflexes. Typically,
progression is slow in MMN and rapid in
PMA.27 The distinction between PMA and
MMN can be a diagnostic issue because
MMN occasionally gives rise to considerable
muscle atrophy, and some patients with PMA
progress slowly.28 Most importantly, however,
PMA is not associated with persistent CB.

TREATMENT OF MMN
The standard evidence-based treatment
of MMN consists of regular courses of IVIG as
shown in 5 double-blind and placebocontrolled trials.2933 Typically, the first
course of IVIG is a cumulative dose 2 g/kg
body weight given over 25 days.2 Assessment of motor function is made after 24
weeks; if there is no improvement, then
reconsider the diagnosis. If there is improvement, then monitor and give a second course
of 2 g/kg when there is deterioration. Subsequent maintenance courses are every 4
weeks, each consisting of 0.4 g/kg given in
1 day, as the clinical response dictates. It
should be emphasized, however, that the

time interval between maintenance courses

and the dosage per maintenance course need
to be tailored for each individual patient on
the basis of regular monitoring of muscle
weakness. Although monitoring has been
performed by Medical Research Council muscle strength, self-evaluation, and overall disability scores, dedicated scoring systems for
MMN are currently being developed.2,34 Side
effects are usually mild and transient and may
include rash, fever, hypotension, hypertension, nausea, headache, and arthralgia. Alternatively, subcutaneous immunoglobulins can
be administered, and their beneficial effects
were shown in a single-blinded trial and
open-label studies (reviewed by Vlam et al2).
Other immunosuppressant and immunomodulatory treatments have been tried.35 Only
1 randomized trial has been conducted with
mycophenolate mofetil, which showed no significant benefit in the reduction of IVIG requirements.36 Corticosteroids are not beneficial and
may worsen symptoms considerably.

PROGNOSIS
MMN progresses slowly and is frequently a diagnostic challenge. Increasing

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Electrodiagnostic Rules in Suspected MMN

awareness of MMN has decreased the median

time to diagnosis from 5 years (range, 115)
in the 19881995 period to 2 years (range,
15) in the 20012006 period.37 Treatment
with IVIG can result in a rapid response with
improved strength but over time, set IVIG
doses may prove insufficient to maintain
strength and higher doses may be needed.
Despite dose adjustments, there occurs progressive axonal loss frequently in affected
nerves with permanent weakness. Axonal
loss may include sensory nerves, resulting in
decreased sensory nerve action potentials or
mild clinical sensory deficits, especially in
nerves with prominent motor axonal loss.4
MMN affects only peripheral nerves and does
not shorten life.
ACKNOWLEDGMENTS
We wish to thank Charlotte Knabel of
BSG Communications for editing assistance. The editorial support provided by
BSG was made possible through funding
provided by Baxter Healthcare.
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