Clinical Neurophysiology 131 (2020) 2804–2808

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Clinical Neurophysiology
journal homepage: www.elsevier.com/locate/clinph

Difference in distribution of fasciculations between multifocal motor

neuropathy and amyotrophic lateral sclerosis
Yukiko Tsuji, Yu-ichi Noto ⇑, Takamasa Kitaoji, Yuta Kojima, Toshiki Mizuno
Department of Neurology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan

a r t i c l e i n f o h i g h l i g h t s

Article history:
 MMN and ALS patients were compared regarding their distribution of fasciculations.
Accepted 17 August 2020
 Fasciculations were detected extensively even in the limbs of MMN patients.
Available online 1 October 2020
 Fasciculations in the tongue and truncal muscles may differentiate ALS from MMN.

Keywords:
Multifocal motor neuropathy
Fasciculation a b s t r a c t
Amyotrophic lateral sclerosis
Muscle ultrasound
Objective: To examine differences in fasciculation distribution between patients with multifocal motor
Ultrasonography neuropathy (MMN) and amyotrophic lateral sclerosis (ALS) based on muscle ultrasound.
Diagnosis Methods: Forty-one muscles (tongue muscle and 40 muscles of the trunk and limbs on both sides) in 5
MMN patients and 21 muscles (tongue muscle and 20 muscles on the onset side) in 21 ALS patients were
subjected to muscle ultrasound individually for 60 seconds to detect the presence of fasciculations.
Results: Fasciculation detection rates on the onset side were significantly higher in ALS (42.4 ± 18.3%,
mean ± SD) than in MMN (21.9 ± 8.8%) patients (p < 0.05). In MMN patients, no fasciculation was detected
in the tongue or truncal muscles. There was no difference in the fasciculation detection rate between the
onset and non-onset sides or between upper and lower limbs in MMN patients.
Conclusions: In MMN patients, fasciculations were detected extensively in the limbs. However, the detec-
tion rate in patients with MMN was lower than in those with ALS.
Significance: Demonstration of the absence of fasciculations in the tongue and truncal muscles in MMN
patients by extensive muscle ultrasound examination may help distinguish MMN from ALS.
Ó 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights
reserved.

1. Introduction Bentes et al., 1999; Brooks et al., 2000) treatable polyneuropathy.

The disease multifocal motor neuropathy (MMN) is a chronic
progressive immune-mediated motor neuropathy. Based on a pre-
vious nerve conduction study, it causes progressive asymmetric
upper-limb-dominant weakness with partial motor conduction
block (Yeh et al., 2020). MMN can mimic amyotrophic lateral scle-
rosis (ALS) because both diseases present with progressive distal-
dominant weakness and fasciculations/cramps without sensory
disturbance (Bentes et al., 1999). The ability to differentiate
MMN from ALS is essential with regard to the treatment and prog-
nosis because MMN is a(Beadon et al., 2018; Beekman et al., 2005;
⇑ Corresponding author at: Kyoto Prefectural University of Medicine Graduate
School of Medical Science, 465 Kajii-cho, Kamigyo-ku, Kyoto City, Kyoto 602-0841,
Japan.
E-mail address: y-noto@koto.kpu-m.ac.jp (Y.-i. Noto).
Although an extensive nerve conduction study and careful inter-
pretation of the results are the gold standards in the diagnosis of
MMN, nerve imaging using ultrasound and MRI recently emerged
as useful techniques to support the diagnosis of MMN (Beadon
et al., 2018; Beekman et al., 2005; Goedee et al., 2017). The neuro-
muscular ultrasound technique is rapidly evolving because of its
accessibility and non-invasiveness. The pre(Goedee et al., 2017)
sence of nerve enlargement detected by nerve ultrasound can sup-
port a diagnosis of MMN by differentiating it from ALS (Grimm
et al., 2015; Loewenbrück et al., 2016). However, the use of ultra-
sound to detect fasciculations has gained much popularity to
increase sensitivity for diagnosing ALS (Misawa et al., 2011;
Johansson et al., 2017; Noto et al., 2017). In our previous study,
employing multi-point muscle ultrasound, fasciculations widely
extended throughout the bodies of ALS patients, and fasciculation
ultrasound scores (FUSs) were higher in ALS patients than in dis-

https://doi.org/10.1016/j.clinph.2020.08.021
1388-2457/Ó 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.
Y. Tsuji, Yu-ichi Noto, T. Kitaoji et al.
ease controls (Tsuji et al., 2017). A previous review reported that
fasciculations may be present in more than 50% of MMN patients
(Nobile-Orazio, 2001). However, the distribution and detection
rate of fasciculations in MMN patients has not been sufficiently
examined, and the utility of FUS to distinguish MMN from ALS
needs to be elucidated because the disease control group in our
previous study did not include MMN patients. As such, the aim
of the present study was to elucidate the characteristics of fascic-
ulations in MMN patients and differences in their distribution
between MMN and ALS patients by extensive muscle ultrasound
examination.
2. Methods
2.1. Subjects
Patients with MMN and ALS were recruited from a neurology
clinic at Kyoto Prefectural University of Medicine hospital from
October 2017 until October 2019. Patients with MMN were diag-
nosed according to the European Federation of Neurosciences/
Peripheral Nerve Society (EFNS/PNS) guidelines (van Schaik et al.,
2006). The presence of serum anti-GM1 antibody was examined
in all MMN patients. At the time of recruitment, all MMN patients
were under maintenance immunotherapy. For ALS, the revised El
Escorial criteria with the Awaji criteria were applied (Brooks
et al., 2000; de Carvalho et al., 2008). Trained neurologists obtained
all patients’ demographic and clinical data, including total Medical
Research Council (MRC) scale sum scores and strength of hand
muscles. Furthermore, the ALS functional rating scale (ALSFRS)
was adopted for ALS patients (Cedarbaum et al., 1999). All patients
gave written informed consent for the procedures, which were
approved by the Ethics Committee of Kyoto Prefectural University
of Medicine.
2.2. Muscle ultrasound
Ultrasound was performed by one examiner (Y.T.) with five
years of experience in neuromuscular ultrasound, blinded to the
clinical history and findings of neurological examinations. A GE
LOGIQ P5 ultrasound system (GE Healthcare Japan, Tokyo, Japan)
was used with a 10-MHz linear-array probe. In all examinations,
the factory preset settings for muscle imaging (depth: 4 cm, width:
4 cm, gain: 54) were used. The tongue (TON), trapezius (TPZ), del-
toid (DEL), biceps brachii (BB), triceps brachii (TB), brachioradialis
(BR), flexor carpi ulnaris (FCU), abductor pollicis brevis (APB),
abductor digiti minimi (ADM), first dorsal interosseous (FDI), 7th
cervical paraspinal (C7PS), 10th cervical paraspinal (T10PS), 5th
lumbar paraspinal (L5PS), abdominal (ABD), rectus femoris (RF),
vastus lateralis (VL), vastus medialis (VM), biceps femoris (BF), tib-
ialis anterior (TA), gastrocnemius (GC), and abductor hallucis (AH)
muscles were examined in each patient. In patients with MMN, 41
muscles (tongue muscle and 40 trunk and limb muscles on both
sides) were examined. In patients with ALS, 21 muscles (tongue
muscle and 20 trunk and limb muscles on the onset side) were
examined. In patients with bulbar-onset ALS, the onset side of limb
muscle weakness was selected as the side for ultrasound examina-
tion (all bulbar-onset ALS patients had limb weakness at the time
of ultrasound assessment). Transverse B-mode moving images
were recorded for each muscle at the standard insertion point in
needle electromyography (EMG) in the supine position with limbs
extended and relaxed. Following the previously reported method-
ology of Noto et al. (Noto et al., 2017), the ultrasound recording
time was set at 60 seconds for each muscle, and the presence of
fasciculations was judged as two or more visible partial muscle
twitches. After judging the existence of fasciculations in all mus-
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Clinical Neurophysiology 131 (2020) 2804–2808
cles, FUSs on the onset side were calculated in each patient. FUS
is a previously developed quantitative score of fasciculations rang-
ing from 0 to 9, defined as follows: the number of muscles with fas-
ciculations detected by ultrasound in TPZ, DEL, BB, APB, ABD, VL,
VM, BF, and GC muscles (Tsuji et al., 2017).
2.3. Nerve conduction studies
Nerve conduction studies were performed in MMN patients
with standard techniques and equipment (MEB-2200 EMG device
(Nihon Kohden, Tokyo, Japan)). The skin temperature was main-
tained above 32 °C. The presence of conduction block (CB) was
assessed in the median and ulnar nerves. CB was defined as a
reduction of the negative compound muscle action potential
(CMAP) area on proximal versus distal stimulation of at least 50%
(van Schaik et al., 2006).
2.4. Data analysis and statistical methods
Fisher’s exact test was used to analyze differences in the sex
ratio and rate of muscles with fasciculations on the onset side
between MMN and ALS cohorts, and the association between CB
in the median and ulnar nerves/weakness and fasciculations in
APB, ADM, and FDI muscles in MMN patients. On the basis of data
features and distribution, a parametric (unpaired t-test) or non-
parametric (Mann-Whitney U test) test was performed to compare
biometric and ultrasound variables on the onset side, including
FUSs, between MMN and ALS patients.
Correlations between fasciculation detection rates in 21 onset-
side muscles (proportion of muscles with fasciculations per 21
examined muscles in each subject) and clinical parameters (age,
disease duration, MRC scale sum score, and ALSFRS-R) were ana-
lyzed by Spearman’s rank correlation test in MMN and ALS groups.
To clarify the distribution pattern of fasciculations, a compar-
ison of fasciculation detection rates in muscles on the onset side
between distal and proximal muscle groups was performed using
Fisher’s exact test in both MMN and ALS groups. In this analysis,
the proximal and distal limb muscle groups were defined as fol-
lows: the distal limb muscle group consisted of FCU, APB, ADM,
FDI, TA, GC, and AH, and the proximal limb muscle group consisted
of DEL, BB, TB, BR, RF, VL, VM, and BF. The rates of muscles with fas-
ciculations in the distal and proximal limb muscle groups were cal-
culated as the proportion of muscles with fasciculations in
examined limb muscles on the onset side using pooled data in each
disease group. In the MMN cohort, fasciculation detection rates in
20 muscles per person excluding the tongue muscles were com-
pared between onset and non-onset sides. The associations among
muscle weakness, CB, and presence of fasciculations were checked
in median and ulnar nerves on both sides. JMP software 12.2 (SAS
Institute, Cary, North Carolina, USA) was used for all statistical
analyses. A P-value of < 0.05 was considered significant. Bonferroni
correction was applied for multiple-correlation analyses.
3. Results
3.1. Clinical characteristics
Five patients with MMN were examined, comprising one possi-
ble and four definite diagnoses of MMN. Three of the five MMN
patients (60%) were anti-GM1 antibody-positive. CB in the median
or ulnar nerve was observed in four of the five patients (80%) (Sup-
plementary Table 1). All MMN patients were responsive to intra-
venous immunoglobulin treatment (IVIG) (Table 1). One patient
was diagnosed with possible MMN due to a lack of CB. A nerve con-
duction study (NCS) showed over a 50% reduction on proximal ver-
Y. Tsuji, Yu-ichi Noto, T. Kitaoji et al. Clinical Neurophysiology 131 (2020) 2804–2808

Table 1
Characteristics of patients with multifocal motor neuropathy.

Patient Diagnostic Disease CB in median or IgM anti-GM1 MRC Responsiveness Rate of muscles with fasciculation in 21 muscles FUS
No. grade duration ulnar nerve antibody sum to IVIg per person on the onset side (%)
(months) score
1 Possible 47 – – 34 + 52.4 7
2 Definite 58 + + 58 + 9.5 2
3 Definite 28 + + 59 + 23.8 2
4 Definite 52 + – 59 + 14.3 1
5 Definite 259 + + 32 + 9.5 0

CB, conduction block; MRC, Medical Research Council; IVIg, intravenous immunoglobulin treatment; FUS, fasciculation ultrasound score.

sus distal stimulation of the CMAP amplitude in both ulnar nerves
of the patient; however, the CMAP amplitudes on proximal stimu-
lation were lower than specified in EFNS/PNS criteria for diagnos-
ing CB. MMN with upper-limb onset was more frequently observed
in the MMN patients. Four of the five patients (80%) were diag-
nosed with MMN with upper-limb onset and one was diagnosed
with lower-limb onset. Regardless of the site of onset, all patients
with MMN had muscle weakness in their upper limbs whereas two
of the five (40%) patients, including the patient with lower-limb-
onset MMN, had muscle weakness in the lower limbs.
The results for MMN patients were compared with those for a
cohort of 21 ALS patients, comprising 4 possible, 6 probable, and
11 definite ALS diagnoses. No ALS patients showed demyelinating
findings including CBs in nerve conduction studies, and we con-
firmed the diagnosis of each patient at follow-up visits. We
matched the sex and age of the ALS cohort, and the ALS group
showed a shorter disease duration than the MMN group
(16.7 ± 11.6 (mean ± SD) vs. 88.8 ± 85.7 months, respectively,
p = 0.002) (Table 2). Regarding muscle weakness in patients with
ALS, onset sites were as follows: bulbar region (33.3%), upper limb
(38.1%), lower limb (28.6%), and thoracic region (0%). ALSFRS was
38.1 ± 7.7 (mean ± SD).
3.2. The characteristics of fasciculations in patients with multifocal
motor neuropathy
A total of 205 muscles were investigated in the MMN group. The
rate of muscles with fasciculations was 21.9% in the examined
muscles on the onset side. Fasciculations were detected mainly
in the limb muscles, and not in the tongue, deltoid, brachioradialis,
nor truncal muscles (abdominal and paraspinal muscles) (Supple-
mentary Fig. 1). The rates of fasciculation-positive muscles in
upper (TPZ, DEL, BB, TB, BR, FCU, APB, ADM, and FDI muscles)
and lower (RF, VL, VM, BF, TA, GC, and AH muscles) limbs were
25.0 ± 20.9 (mean ± SD) and 27.1 ± 26.5%, respectively. Fascicula-
tions were detected in at least one lower-limb muscle in all
MMN patients. Even in three upper-limb-onset MMN patients
without lower-limb-muscle weakness, fasciculations were
detected in half of their lower-limb muscles. When detection rates
were compared between the onset and non-onset sides, it was not
significantly different (23% in the onset-side muscles except for the
tongue muscle and 23% in the non-onset-side muscles except for
the tongue muscle). The rates of fasciculation-positive muscles
on the onset side did not correlate with clinical parameters in
MMN patients. In addition, there was no significant correlation
between the presence of fasciculations and CB/muscle weakness
in hand muscles (Supplementary Table 2). Two of 30 hand mus-
cles in MMN patients showed fasciculations but no CB nor muscle
weakness.
3.3. Comparison of the detection rate and distribution pattern of
fasciculations between multifocal motor neuropathy and amyotrophic
lateral sclerosis
In patients with ALS, 441 muscles were examined, and the rate
of muscles with fasciculations on the onset side was higher than
that in MMN patients (42.4 vs. 21.9%, respectively, P < 0.001).
There was no difference in fasciculation detection rates between
distal and proximal limb muscle groups in MMN and ALS cohorts
(34.3 and 22.5% in the MMN group (p = 0.31), and 49.0 and
54.8% in the ALS group (p = 0.31), respectively). Fasciculations in
the tongue, deltoid, brachioradialis, and abdominal muscles were
detected only in patients with ALS (Supplementary Fig. 1). No cor-
relation between the fasciculation detection rate of muscle and
clinical parameters was detected in ALS patients.
3.4. Fasciculation ultrasound score
FUSs on the onset side were 2 ± 1 (median ± interquartile range
(IQR) (range: 0 to 7) in patients with MMN and 5 ± 2 (range: 1 to 9)
in those with ALS; FUSs in the former patients were significantly
lower than those in the latter (P = 0.035).
4. Discussion

Table 2 In MMN, fasciculations were detected extensively in the limbs

Parameters of patients with multifocal motor neuropathy and amyotrophic lateral by muscle ultrasound. However, the fasciculation detection rate
sclerosis. in all muscles of MMN patients was lower than that in ALS
MMN ALS p-value patients. In addition, FUS in MMN patients was also lower than
that in ALS patients. Although the clinical finding that fascicula-
n (male) 5 (5) 21 (13) 0.097
Age (mean ± SD) 53 ± 14.6 68 ± 9.2 0.102 tions in the tongue and truncal muscles are absent in MMN
Disease duration (month, mean ± SD) 88.8 ± 85.7 16.7 ± 11.6 0.002* patients may be common knowledge among neurologists, objec-
MRC sum score 48.4 ± 12.6 51.8 ± 7.0 0.630 tive evidence is scarce. The present study objectively confirmed
ALSFRS (mean ± SD) N/A 38.1 ± 7.7 N/A
the absence of fasciculations in the tongue and truncal muscles
Rate of muscles with fasciculation in 21.9 ± 8.8 42.4 ± 18.3 <0.001*
21 muscles per person on the onset
in MMN patients, which could be a pivotal point to differentiate
side (%) MMN from ALS.
FUS (median [IQR]) 2 [1–3] 5 [3–7] 0.035* Fasciculations and cramps are prominent symptoms in MMN,
MMN, multifocal motor neuropathy; ALS, amyotrophic lateral sclerosis; MRC,
observed in up to 40–50% of patients (Nobile-Orazio, 2001; Yeh
Medical Research Council; FUS, fasciculation ultrasound score; SD, standard devi- et al., 2020), whereas fasciculations are almost always present in
ation; IQR, interquartile range; N/A, not available; *, p < 0.05. ALS patients and are included in the diagnostic criteria as a clinical
2806
Y. Tsuji, Yu-ichi Noto, T. Kitaoji et al.
indicator of lower motor neuron dysfunction (Brooks et al., 2000;
de Carvalho et al., 2017). The presence of fasciculations in both dis-
eases is one of the reasons why it is challenging to differentiate
MMN from ALS. The muscle motion of fasciculations is also similar
between MMN and ALS (Supplementary Video 1). However, nee-
dle EMG characteristics of fasciculations in MMN patients have not
been thoroughly investigated because the detection of CB is promi-
nent in the diagnosis of MMN, and needle EMG is not always
needed to achieve a diagnosis. The present study revealed that
the rate of muscles with fasciculations on the onset side in MMN
patients was significantly lower than that in ALS patients when
ultrasound examination was performed at multiple sites.
In addition, fasciculations were not detected in the tongue, del-
toid, abdominal, or paraspinal muscles of MMN patients. The
pathogenesis of fasciculations remains to be determined. In ALS,
fasciculations are considered to arise both in the upper and lower
motor neuron compartments, associated with the motor cortex
and axonal hyperexcitability (de Carvalho et al., 2017; Noto et al.,
2018). From the viewpoint of the pathology of MMN, fasciculations
may be generated solely from the lower motor neuron compart-
ment, which shows altered axonal excitability in MMN (Kiernan
et al., 2002). Although knowledge is limited, variation in the origin
of fasciculations between MMN and ALS may lead to their distribu-
tional differences.
The relationships between the distribution pattern of fascicula-
tions and symptoms have yet to be elucidated, although some pre-
vious studies revealed an association between CB and axonal loss
detected by NCS and the weakness of innervated muscle (Van
Asseldonk et al., 2003; Vucic et al., 2007). In the present study,
there was no tendency toward onset side-dominant detection of
fasciculations in MMN patients. Also, many (50%) fasciculations
were detected in lower-limb muscles without weakness in
upper-limb-onset MMN patients. Furthermore, sub-analysis
involving hand muscles identified no correlation between the pres-
ence of fasciculations and median and ulnar nerve CB/innervated
muscle weakness. Similar to NCS abnormalities noted in previous
studies (Van Asseldonk et al., 2003; Vucic et al., 2007), fascicula-
tions can also occur in MMN patients, irrespective of the onset limb
or affected muscles. Although a widespread pattern of fascicula-
tions is considered pathognomonic of ALS (Johansson et al., 2017;
Tsuji et al., 2017; Noto et al., 2018), we should pay attention to
the fact that an extensive distribution of fasciculations in limb
muscles cannot exclude a diagnosis of MMN.
FUS that we developed was initially applied to our MMN cohort
because no MMN patients were included in the disease control
group of our previous study (Tsuji et al., 2017). In that study, FUS
of two or more showed high sensitivity and specificity in differen-
tiating ALS from non-ALS. In the present study, the median FUS in
MMN patients was two, being significantly lower than in ALS
patients. To make FUS more useful in differentiating ALS from
ALS mimics including MMN, further validation studies involving
larger numbers of MMN patients and re-examinations of the selec-
tion of muscles and cut-off value are necessary.
The small number of patients and lack of treatment-naïve
patients with MMN were limitations of the present study. A previ-
ous study reported no significant change in the amount of fascicu-
lation potentials in five patients with MMN from before until after
immunoglobulin therapy (Comi et al., 1994). However, it is still
unclear whether repeated /continuous immunologic treatments
affect the frequency of fasciculations. A future fasciculation study
involving a comparison between untreated patients with MMN
and patients with ALS is necessary. The future analysis of changes
in the distribution and frequency of fasciculations before and after
treatment in a larger MMN cohort will be needed to elucidate their
pathogenesis and significance in MMN. Furthermore, we included
bulbar-onset ALS patients in the ALS cohort of the present study
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Clinical Neurophysiology 131 (2020) 2804–2808
because there was no significant difference in the distributions of
fasciculations among the upper limb, lower limb, and bulbar-
onset groups (Tsuji et al., 2017; Takamatsu et al., 2016). When
we note clinically evident tongue muscle fasciculations on physical
examination, it is easy to exclude the diagnosis of MMN and deter-
mine that muscle ultrasound examination is not needed. On the
other hand, CB is not always detectable when extensive NCS is per-
formed (Cats et al., 2010), which makes the diagnosis of MMN chal-
lenging in patients with limb-onset weakness. To clarify the utility
of muscle ultrasound, further studies including challenging cases
without bulbar muscle dysfunction are necessary.
In conclusion, fasciculations were absent in the tongue and
truncal muscles in MMN patients, unlike the findings in ALS
patients, although fasciculations were detected extensively in the
limbs of MMN patients. Also, the detection rate of fasciculations
in patients with MMN was lower than in those with ALS. These dif-
ferences in the distribution and rate of fasciculations detected by
extensive muscle ultrasound examination may help distinguish
MMN from ALS.
Acknowledgements
This research was supported by Japan Society for the Promotion of
Science KAKENHI Grant Number 19K17041.
Declaration of Competing Interest
None of the authors has potential conflicts of interest to
disclose.
Appendix A. Supplementary material
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.clinph.2020.08.021.
References
Beadon K, Guimarães-Costa R, Léger J-M. Multifocal motor neuropathy:. Curr Opin
Neurol 2018;31(5):559–64.
Beekman R, van den Berg LH, Franssen H, Visser LH, van Asseldonk JTH, Wokke JHJ.
Ultrasonography shows extensive nerve enlargements in multifocal motor
neuropathy. Neurology 2005;65(2):305–7.
Bentes C, de Carvalho M, Evangelista T, Sales-Luı´s ML. Multifocal motor neuropathy
mimicking motor neuron disease: nine cases. J Neurol Sci 1999;169(1-2):76–9.
Brooks BR, Miller RG, Swash M, Munsat TL. El Escorial revisited: Revised criteria for
the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Sclerosis
Other Motor Neuron Disorders 2000;1(5):293–9.
Cats EA, van der Pol W-L, Piepers S, Franssen H, Jacobs BC, van den Berg-Vos RM,
Kuks JB, van Doorn PA, van Engelen BG, Verschuuren JJ, Wokke JH, Veldink JH,
van den Berg LH. Correlates of outcome and response to IVIg in 88 patients with
multifocal motor neuropathy. Neurology 2010;75(9):818–25.
Cedarbaum JM, Stambler N, Malta E, Fuller C, Hilt D, Thurmond B, Nakanishi A. The
ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of
respiratory function. J Neurol Sci 1999;169(1-2):13–21.
de Carvalho M, Dengler R, Eisen A, England JD, Kaji R, Kimura J, Mills K, Mitsumoto
H, Nodera H, Shefner J, Swash M. Electrodiagnostic criteria for diagnosis of ALS.
Clin Neurophysiol 2008;119(3):497–503.
de Carvalho M, Kiernan MC, Swash M. Fasciculation in amyotrophic lateral
sclerosis: origin and pathophysiological relevance. J Neurol Neurosurg
Psychiatry 2017;88(9):773–9.
Comi G, Amadio S, Galardi G, Fazio R, Nemni R. Clinical and neurophysiological
assessment of immunoglobulin therapy in five patients with multifocal motor
neuropathy.. J Neurol Neurosurg Psychiatry 1994;57(Suppl):35–7.
Goedee HS, Jongbloed BA, van Asseldonk J-T- H, Hendrikse J, Vrancken AFJE,
Franssen H, Nikolakopoulos S, Visser LH, van der Pol WL, van den Berg LH. A
comparative study of brachial plexus sonography and magnetic resonance
imaging in chronic inflammatory demyelinating neuropathy and multifocal
motor neuropathy. Eur J Neurol 2017;24(10):1307–13.
Grimm A, Décard BF, Athanasopoulou I, Schweikert K, Sinnreich M, Axer H. Nerve
ultrasound for differentiation between amyotrophic lateral sclerosis and
multifocal motor neuropathy. J Neurol 2015;262(4):870–80.
Johansson MT, Ellegaard HR, Tankisi H, Fuglsang-Frederiksen A, Qerama E.
Fasciculations in nerve and muscle disorders – A prospective study of muscle
Y. Tsuji, Yu-ichi Noto, T. Kitaoji et al.
ultrasound compared to electromyography. Clin Neurophysiol 2017;128
(11):2250–7.
Kiernan MC, Guglielmi J-M, Kaji R, Murray NMF, Bostock H. Evidence for axonal
membrane hyperpolarization in multifocal motor neuropathy with conduction
block. Brain 2002;125(3):664–75.
Loewenbrück KF, Liesenberg J, Dittrich M, Schäfer J, Patzner B, Trausch B, Machetanz
J, Hermann A, Storch A. Nerve ultrasound in the differentiation of multifocal
motor neuropathy (MMN) and amyotrophic lateral sclerosis with predominant
lower motor neuron disease (ALS/LMND). J Neurol 2016;263(1):35–44.
Misawa S, Noto Y, Shibuya K, Isose S, Sekiguchi Y, Nasu S, Kuwabara S.
Ultrasonographic detection of fasciculations markedly increases diagnostic
sensitivity of ALS. Neurology 2011;77(16):1532–7.
Nobile-Orazio E. Multifocal motor neuropathy. J Neuroimmunol 2001;115(1-
2):4–18.
Noto Y-I, Shibuya K, Shahrizaila N, Huynh W, Matamala JM, Dharmadasa T, Kiernan
MC. Detection of fasciculations in amyotrophic lateral sclerosis: The optimal
ultrasound scan time: Ultrasound for Fasciculations. Muscle Nerve 2017;56
(6):1068–71.
Noto Y-I, Simon NG, Selby A, Garg N, Shibuya K, Shahrizaila N, Huynh W, Matamala
JM, Dharmadasa T, Park SB, Vucic S, Kiernan MC. Ectopic impulse generation in
peripheral nerve hyperexcitability syndromes and amyotrophic lateral
sclerosis. Clin Neurophysiol 2018;129(5):974–80.
2808
Clinical Neurophysiology 131 (2020) 2804–2808
Takamatsu N, Nodera H, Mori A, Maruyama-Saladini K, Osaki Y, Shimatani Y, Oda M,
Izumi Y, Kaji R. Which muscle shows fasciculations by ultrasound in patients
with ALS?. J Med Invest 2016;63(1.2):49–53.
Tsuji Y, Noto Y-I, Shiga K, Teramukai S, Nakagawa M, Mizuno T. A muscle ultrasound
score in the diagnosis of amyotrophic lateral sclerosis. Clin Neurophysiol
2017;128(6):1069–74.
Van Asseldonk JTH, Van den Berg LH, Van den Berg-Vos RM, Wieneke GH, Wokke
JHJ, Franssen H. Demyelination and axonal loss in multifocal motor neuropathy:
distribution and relation to weakness. Brain 2003;126(1):186–98.
van Schaik IN, Bouche P, Illa I, Leger J-M, Van den Bergh P, Cornblath DR, Evers EMA,
Hadden RDM, Hughes RAC, Koski CL, Nobile-Orazio E, Pollard J, Sommer C, van
Doorn PA. European Federation of Neurological Societies/Peripheral Nerve
Society guideline on management of multifocal motor neuropathy*. Eur J
Neurol 2006;13(8):802–8.
Vucic S, Black K, Tick Chong PS, Cros D. Multifocal motor neuropathy with
conduction block: Distribution of demyelination and axonal degeneration. Clin
Neurophysiol 2007;118(1):124–30.
Yeh WZ, Dyck PJ, van den Berg LH, Kiernan MC, Taylor BV. Multifocal motor
neuropathy: controversies and priorities. J Neurol Neurosurg Psychiatry
2020;91(2):140–8.