Characterization of Fasciculation Potentials (FPs) in Amyotrophic Lateral Sclerosis (ALS) and Peripheral Nerve Hyperexcitability Syndromes (PNH)

Abstract

This study is aimed at investigating the features of fasciculation potentials (FPs) in amyotrophic lateral sclerosis (ALS) and peripheral nerve hyperexcitability syndromes (PNH). Needle electrophysiologic examination (EMG) was performed for 5-15 muscles in the ALS and PNH patients. The spontaneous activity of fasciculations and fibrillations/sharp-waves (fibs-sw) was recorded. The distribution, firing frequency, and waveform parameters of FPs in muscles were calculated and compared. In total, 361 muscles in ALS patients and 124 muscles in PNH patients were examined, with the FP detection rates of 45.1% and 53.2%. Moreover, the ALS patients with the upper limb onset had the highest FP detection rate. Fasciculations occurred more frequently in the upper limbs than in the lower limbs in ALS and PNH. The detection rate of fibs-sw in the bulbar muscle was relatively low, which could be elevated when combining fibs-sw and FPs. Benign FPs in PNH were of smaller amplitude, shorter duration, and fewer phases/turns, compared with malignant FPs in ALS. The FP area in PNH was significantly smaller than that in ALS. The incidence of polyphasic FPs in ALS was distinctly greater than that in PNH. The firing frequency of FPs in PNH was higher than that in ALS. There was no significant difference in the amplitude, duration, phases and turns, and area of FPs between groups with and without fibs-sw in the muscles of normal strength in ALS. Conclusively, it is necessary to detect the FPs in the thoracic and bulbar muscles of patients suspected having ALS. FP parameters in ALS are significantly different from PNH.

Full text

Research Article
Characterization of Fasciculation Potentials (FPs) in Amyotrophic
Lateral Sclerosis (ALS) and Peripheral Nerve Hyperexcitability
Syndromes (PNH)
Hua Wang ,
1
Bin Liu ,
2
and Jiyou Tang
3
1
Department of Neurology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, China
2
Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, China
3
Department of Neurology, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250014, China
Correspondence should be addressed to Jiyou Tang; tjiyou@yahoo.com
Received 10 October 2020; Revised 22 March 2021; Accepted 17 April 2021; Published 3 May 2021
Academic Editor: Quintino Giorgio D'alessandris
Copyright © 2021 Hua Wang et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
This study is aimed at investigating the features of fasciculation potentials (FPs) in amyotrophic lateral sclerosis (ALS) and
peripheral nerve hyperexcitability syndromes (PNH). Needle electrophysiologic examination (EMG) was performed for 5-15
muscles in the ALS and PNH patients. The spontaneous activity of fasciculations and fibrillations/sharp-waves (fibs-sw) was
recorded. The distribution, firing frequency, and waveform parameters of FPs in muscles were calculated and compared. In
total, 361 muscles in ALS patients and 124 muscles in PNH patients were examined, with the FP detection rates of 45.1% and
53.2%. Moreover, the ALS patients with the upper limb onset had the highest FP detection rate. Fasciculations occurred more
frequently in the upper limbs than in the lower limbs in ALS and PNH. The detection rate of fibs-sw in the bulbar muscle was
relatively low, which could be elevated when combining fibs-sw and FPs. Benign FPs in PNH were of smaller amplitude, shorter
duration, and fewer phases/turns, compared with malignant FPs in ALS. The FP area in PNH was significantly smaller than that in
ALS. The incidence of polyphasic FPs in ALS was distinctly greater than that in PNH. The firing frequency of FPs in PNH was
higher than that in ALS. There was no significant difference in the amplitude, duration, phases and turns, and area of FPs between
groups with and without fibs-sw in the muscles of normal strength in ALS. Conclusively, it is necessary to detect the FPs in the
thoracic and bulbar muscles of patients suspected having ALS. FP parameters in ALS are significantly different from PNH.
1. Introduction
Fasciculations have long been recognized as a dominant
characteristic and early feature of amyotrophic lateral sclero-
sis (ALS), which can be detected in a wide range of muscles in
the body of ALS patients. However, fasciculation potentials
(FPs) can indicate ALS only when combined with the pro-
gressive limb weakness, atrophy, and/or increased tendon
reflexes from the physical examination and neurogenic
defects from the electrophysiologic examination (EMG) [1].
Not all affected muscles in ALS patients can display FPs,
and not all muscles with FPs are associated with neurogenic
damages. Normal muscles in some patients may develop
FPs [2], which also could be frequently detected in the
peripheral nerve hyperexcitability syndromes (PNH) [3].
PNH includes a series of diseases such as the cramp-
fasciculation syndrome, benign fasciculation syndrome
(BFS), Isaac’s syndrome, and Morvan syndrome. Spontane-
ous discharges (including fasciculations, doublets, triplets,
or multiplets), as well as myokymic discharges and myotonic
discharges, which are usually detected by the needle EMG in
muscles of PNH patients [4, 5]. Patients with symptoms of
muscle twitches and cramps who may suffer from chronic
fatigue syndrome (CFS) would struggle to get a diagnosis
for years or come to the department of neurology because
of the symptom of fasciculations. According to the Awaji cri-
teria proposed in 2008 [6], fasciculations and fibrillations/-
sharp-waves (fibs-sw) should share similar and equivalent
importance in the diagnosis in ALS with EMG. Thus, the
detection and observation of FPs should be highlighted
Hindawi
BioMed Research International
Volume 2021, Article ID 6631664, 12 pages
https://doi.org/10.1155/2021/6631664

during EMG. However, there are few articles describing the
prevalence of FPs in needle EMG for ALS and PNH.
In ALS, FPs are expected to have a more complex, insta-
ble morphology, which may be involved in normal muscles
of a clinically unrelated body region [6]. Nevertheless, it has
been reported to be difficult to distinguish the benign and
malignant fasciculations just based on the waveform [7].
Concerning the detection rates of malignant and benign
FPs, a previous study has revealed that the firing rates in
three patients with BFS in the upper limb muscles were
higher than those with ALS [8]. However, a recent article
has shown an opposite result that the FP firing frequencies
in the muscles of ALS patients were significantly higher than
those of the PNH patients [9]. In this study, the prevalence,
firing pattern, and waveforms of FPs in ALS and PNH were
investigated. How the clinicians could benefit of the detection
of FPs was studied and analyzed.
2. Patients and Methods
2.1. Study Subjects. A total of 55 patients, including 36
patients with ALS and 19 patients with PNH, were enrolled
in this study. The 36 patients with ALS were admitted to
the EMG Laboratories of Shandong Provincial Hospital,
from April 2018 to June 2019. In addition, the 19 patients
with PNH were admitted from July 2017 to June 2019. All
of the 36 patients with ALS had a progressive history of mus-
cle weakness and/or muscle atrophy in one or more body
regions, with/without muscle stiffness, for at least 4 months.
Complete neurological examination and electromyography
were performed. According to the findings from the labora-
tory and imageological examinations, patients with diabetes,
focal radicular neuropathy, multifocal motor neuropathy,
cervical spondylosis, and syringomyelia were excluded. There
were three patients showing rapid progress in the EMG
Table 1: Demographic characteristics and fasciculation detection rate in muscles of ALS and PNH.
ALS (n=36) PNH (n=19)p
Gender (M : F) 27 : 9 10 : 9 0.388
Age (years) 59.6 (8.2) 54.0 (14.8) <0.001
Disease duration (month) 15.6 (10.6) 20.0 (31.3) <0.001
ALSFRS-R 39.8 (5.5) N/A N/A
Overall fasciculation detection rate (%) 45.1 (163/361) 53.2 (66/124) <0.001
The data of age, disease duration, and ALSFRS-R were shown as the mean (SD). ALS: amyotrophic lateral sclerosis; PNH: peripheral nerve hyperexcitability
syndrome; and ALSFRS-R: revised ALS Functional Rating Scale.
12
22
oracicBulbar Uppar limb Lower limb
Region of onset
100.0
80.0
60.0
40.0
20.0
.0
Detection rate of fasciculations
Figure 1: Fasciculation detection rates for ALS classified by an onset site.
2 BioMed Research International

follow-up within six months, and the data of their last
examination were included in the study. Ultimately, accord-
ing to the revised El Escorial and the Awaji criteria [6, 10],
35 of the recruited patients were classified as probable or
definite ALS, while only 1 patient as unclassified. The dis-
ease onset occurred in the upper limb in 21 patients, lower
limb in 8 patients, bulbar in 5 patients, and respiratory
onset (spinal origin) in 2 patients. The syndromes of PNH
included the muscle twitches, cramps, stiffness, and myoky-
mia, as well as wide spread of fasciculations. Moreover, the
pseudomyotonia and muscle hypertrophy would also be
observed. Some of the patients with PNH were accompa-
nied by the hyperhidrosis, insomnia, hallucination, memory
loss, epilepsy, and pathological pain, due to the immunolog-
ical basis associated with antibodies to VGKCs and AChRs.
Moreover, in these 19 patients with PNH, three exhibited
transient weakness of the limbs and body muscles, and the
laboratory tests showed hypokalemia. One of these 3
patients also showed the hypocalcemia and hypermagnese-
mia due to the electrolyte disorder caused by the Sjogren’s
syndrome. In one patient complaining of memory loss, sei-
zure, continuous muscle twitching, and coxal muscle spasm,
the leucine-rich glioma-inactivated protein1 associated with
limbic encephalitis was detected. In addition, two out of the
CFS patients were combined with the mild L5-S1 radiculo-
pathy in the lower limbs according to the EMG examina-
tion, and however, only the fasciculations in the upper
limbs were included herein for the analysis of FP morphol-
ogy. There was another patient of CFS with a history of
mild hoarseness and dysphagia for 2 years, who was
enrolled in the Emergency Ward, with hypoxemia due to
acute laryngeal paralysis before the EMG examination.
Moreover, one patient with CFS for more than 20 years
had a mild sensory nerve defect. Another patient with
Isaacs’syndrome had a significant reduction in the wide-
spread muscle twitching due to pregnancy. Only one subject
of the 19 PNH patients had suffered from kidney cancer for
4 years. Patients in the PNH group had different disease
durations, and the patients diagnosed with Isaacs’or Mor-
van syndrome had relatively shorter symptom histories
(with the mean value of 1.8 m) than those diagnosed with
CFS/MFS (with the mean value of 34.6 m).
80.0
60.0
40.0
20.0
0.0
TON SCM TPZ DEL BB FCR EDC APB FDI T8PS T10PS ABD IP QUAD TA GC GM AH
Muscles
Detection rate of fasciculation (%)
ALS group
PNH group
Figure 2: Fasciculation detection rates by needle EMG on each muscle. The fasciculation detection rates by needle EMG on each muscle were
analyzed and compared between the ALS and PNH groups. ALS: amyotrophic lateral sclerosis; PNH: peripheral nerve hyperexcitability
syndrome; TON: tongue; SCM: sternocleidomastoid; TPZ: upper trapezius; DEL: deltoid; BB: biceps brachialis; FCR: flexor carpi radialis;
EDC: extensor digitorum communis; FDI: first dorsal interosseous; APB: abductor pollicis brevis; ABD: rectus abdominis; T8PS and
T10PS: 8
th
and 10
th
thoracic paraspinal; QUAD: quadriceps femoris; IP: iliopsoas; TA: tibialis anterior; GM: gluteus maximus; AH:
abductor hallucis.
3BioMed Research International

All subjects gave their informed consents, and the pro-
tocol was approved by the local research ethic committee.
2.2. EMG Detection. All of the 55 patients underwent the
accurate neurological examination before the EMG detec-
tion, including the LMN related muscle force (MRC scales
0-5), sign of atrophy, and distribution of fasciculations in 4
body regions. Besides, the tendon reflexes and muscle spas-
ticity, plantar response, Hoffman sign, and jaw reflex were
also evaluated, which might indicate the UMN functional
defect. The disease severities in the patients with ALS were
evaluated by the revised ALS Functional Rating Scale.
Needle electromyography and nerve conduction using
the electromyographic machine (MEB 9200K, NIHONKOH-
DEN) were performed, with the filter of 10-5 kHz. The skin
temperature was maintained greater than 32
°
C. At least 6
nerves of the upper and lower limbs were examined, and all
the patients were excluded from the significant sensory nerve
damages and motor nerve conduction block. Then, 8-15
muscles (a total of 361) in each ALS patient and 5-9 (a total
of 124) muscles in the PNH group were subjected to the test
for spontaneous activity of fasciculations and fibs-sw. The
frequently examined muscles in different body regions in
each patient included the tongue, sternocleidomastoid, upper
trapezius, deltoid, biceps brachialis, extensor digitorum
communis, first dorsal interosseous, abductor pollicis brevis,
rectus abdominis, 8
th
and 10
th
thoracic paraspinal, iliopsoas,
vastus medialis, tibialis anterior, gluteus maximus, and
abductor hallucis. The actual number and range of muscles
examined were adjusted by the distribution of fasciculations
and the weakness complained by the patient. Most patients
could cooperate with the needle EMG examination and kept
the examined muscles relaxed.
fibs-sw and fasciculations (especially FPs) were explored
in at least 6 sites, lasting for at least 120 s for each muscle.
The fibs-sw was defined as the regularly firing potentials
(duration < 5 ms and amplitude < 1 mV) that lasted for more
than 3 s, and the fasciculations were recognized as the motor
unit potential-shaped potentials with more than 50 μV, firing
in a high irregular pattern. FPs showing not only once were
included for the firing frequency calculation (total of 75),
and the detection rate of FPs in each muscle was calculated.
TON
SCM
TPZ
DEL
BB
FCR
EDC
APB
FDI
T8PS
T10PS
ABD
IP
QUAD
TA
GC
GM
AH
0204060
Number
Muscle
ALS group
PNH group
Figure 3: Analysis of examined muscle numbers. The numbers of muscles examined were analyzed and compared between the ALS and PNH
groups. ALS: amyotrophic lateral sclerosis; PNH: peripheral nerve hyperexcitability syndrome; TON; tongue; SCM: sternocleidomastoid;
TPZ: upper trapezius; DEL: deltoid; BB: biceps brachialis; FCR: flexor carpi radialis; EDC: extensor digitorum communis; FDI: first dorsal
interosseous; APB: abductor pollicis brevis; ABD: rectus abdominis; T8PS and T10PS: 8
th
and 10
th
thoracic paraspinal; QUAD: quadriceps
femoris; IP: iliopsoas; TA: tibialis anterior; GM: gluteus maximus; AH: abductor hallucis.
4 BioMed Research International

All the FPs detected (783 in the ALS group and 183 in the
PNH group) were saved offline for the further analysis and
comparison of amplitude, duration, phases, turns, and area.
Complex or malignant FPs were defined as those having
either more than 4 phases or increased amplitude and/or
duration, compared to normal values of motor unit poten-
tials in the specific muscle. Due to the fact that the data of
FPs from different muscles were included herein, it was diffi-
cult to analyze and compare the duration and amplitude and
area of the FPs, with the normal muscles. Therefore, complex
FPs were simply defined as the FPs with more than 4 phases
herein. Combined FPs were also noticed, which were how-
ever not analyzed separately.
2.3. Statistical Analysis. The FPs detected in the ALS patients
were divided into 3 groups according to the muscle strength:
G1, normal muscle strength (MRC5) group; G2, slightly
weak muscle (MRC4) group; and G3, moderately or severely
weak muscle (MRC3 and below) group. The FPs detected in
the muscles of normal strength in the ALS patients were sep-
arately analyzed according to the presence or absence of fibs-
sw in the muscle.
Statistical analysis was performed using the SPSS 22.0
software (IBM, USA). Pearson χ2test was used to analysis
the difference in the gender composition between the PNH
and ALS patients. The Mann–Whitney Utest and Kruskal
Wallis test were used to analyze the FP amplitude, duration,
area, phases, turns, and firing frequencies between the ALS
subgroups and PNH group. The polyphasic FP ratio between
groups was compared using the contingency tables. p<0:05
was considered statistically significant.
3. Results
3.1. Distribution and Detection Rates of FPs. In total, 36
patients with ALS and 19 patients with PNH were recruited
herein. Spontaneous potentials (FPs and fibs-sw) of 361 mus-
cles in the ALS group and 124 muscles in the PNH group were
analyzed (Table 1). The distribution and detection rates of FPs
were analyzed and compared. Our results showed that the
total detection rates of fasciculations were 45.1% and 53.2%
for the ALS and PNH groups, respectively (p<0:001). How-
ever, the average number of muscles involved in the detection
was less in the PNH group (6.87) compared with the ALS
group (10.38) (p<0:001). Classified based on the onset region,
the upper limb onset group of ALS had the highest FP detec-
tion rate (49.64%), similar to the lower limb onset group
(46.50%), both of which were higher than the bulbar and tho-
racic onset group in the ALS patients (Figure 1).
The detection rates of FPs in each muscle were analyzed
and compared between the ALS and PNH groups. As shown
in Figure 2, the detection rates of FPs in the lower limb mus-
cles, rectus abdominis, and most of the upper limb muscles in
the PNH group were slightly higher than those in the ALS
group. The muscles examined with the FP detection rates
that were approximately equal to or greater than 50%
included the upper trapezius, biceps brachialis, extensor digi-
torum communis, abductor pollicis brevis, and first dorsal
interosseous in the ALS group and the deltoid, extensor digi-
torum communis, abductor pollicis brevis, first dorsal inter-
osseous, tibialis anterior, gluteus maximus, and abductor
hallucis in the PNH group. Fasciculations occurred signifi-
cantly more frequently in the upper limbs than in the lower
limbs in both the ALS and PNH groups. The mean FP
1.28% 0.13% 0.51%
35.50%
47.64%
14.94%
543210
50
40
30
20
10
0
Percentage of detected FPs
MRC
Figure 4: Percentage of FPs detected in different muscle strength groups. The number and percentage of FPs detected in the different muscle
strength groups in all FPs in ALS were analyzed. MRC: medical research council.
5BioMed Research International

detection rates in the upper and lower limbs were 54.7% and
34.6% in the ALS group, which were 63.6% and 52.5% in the
PNH group. Fasciculations occurred slightly more often in
the proximal extremity (median, 55%) than the distal mus-
cles of upper limb (median, 51.7%). Meanwhile, they were
more often detected in the distal extremities (median,
70%) than in the proximal upper limb muscles (median,
50%). Although the detection rates of FPs in some muscles
(e.g., in the upper trapezius, deltoid, gluteus maximus, and
abductor hallucis) were higher than 60%, the number of
these muscles examined in this study was actually not high
(Figure 3).
Fasciculations were more easily detected in the slightly
weak muscles (MRC4, 47.6%) in the ALS patients than in
the normal strength muscle (MRC5, 35.5%). The incidence
of FPs in the moderately or severely weak muscles (MRC3
and below, 16.9%) was significantly lower than that in the
normal strength or slightly weak muscles (Figure 4).
The fibs-sw at more than two sites examined in the mus-
cle by the needle EMG was considered abnormal. The detec-
tion rate of fibs-sw in the bulbar muscle was relatively low
(tongue 23.7% and sternocleidomastoid 29.7%). Given the
difficulty of patient coordination in the muscle examination
of bulbar muscles, it was impossible to distinguish the fibs-
sw due to the incomplete relaxation, in about 10% (or less)
of the examined lingual muscles. On the other hand, the
FPs of the bulbar muscle were more easily to detected, with
the detection rates of 42.1% and 44.4%, respectively, for the
tongue and sternocleidomastoid. There were 8 and 9 more
patients showing the FPs in the bulbar muscles without
denervation activity. Therefore, combined with the sponta-
neous activity of FPs and fibs-sw, the whole neurogenic
detection rate of the bulbar muscles could be significantly
improved, approximately 50.0% and 54.1% for the tongue
and sternocleidomastoid, respectively. Although the biceps
had a positive rate of 73.5% of fibs-sw, there were another 6
muscles showing FPs, and a combined 91.2 neurogenic activ-
ity was accomplished. The same phenomenon occurred in
the anterior tibialis, covering from 51.3% to 71.9% (Figure 5).
In general, the distribution of FPs in each body region
was not consistent with the fibs-sw. When the denervation
activity occurred in no more than 3 individual body regions,
the distribution of FPs was more extensive than fibs-sw, with
an incidence of 47.8% (11/23). However, when the fibs-sw
was widely distributed (3 or 4 body regions), the distribution
range of FPs was decreased correspondingly. In the body
regions not clinically affected, the FPs and denervation activ-
ities could be examined. Our results showed that 63.9%
(23/36) of the patients showed fibs-sw or FPs in the body
regions not clinically involved (Figure 6).
100.0
80.0
60.0
40.0
20.0
2.0
TON SCM TPZ DEL BB EDC APB FDI T8PS T10PS ABD IP QUAD TA GC
Muscles in ALS
Detection rate (%)
bs-sw
bs-sw combined Ps
Figure 5: Detection rate of spontaneous activity combined with fibs-sw and FPs in each muscle examined in ALS. fibs-sw: fibrillations/sharp-
waves; FPs: fasciculation potentials; ALS: amyotrophic lateral sclerosis; PNH: peripheral nerve hyperexcitability syndrome; TON: tongue;
SCM: sternocleidomastoid; TPZ: upper trapezius; DEL: deltoid; BB: biceps brachialis; EDC: extensor digitorum communis; FDI: first
dorsal interosseous; APB: abductor pollicis brevis; ABD: rectus abdominis; T8PS and T10PS: 8
th
and 10
th
thoracic paraspinal; QUAD:
quadriceps femoris; IP: iliopsoas; TA: tibialis anterior.
6 BioMed Research International

3.2. Characterization of FPs. The shape and frequency of FPs
discharging more than once were observed. Repeated
released FPs in the PNH group were generally simple and sta-
ble (Figure 7). However, most the FPs repeatedly recorded in
the ALS group showed morphological diversity, complexity,
and instability (Figure 8). Besides, the rate of stable FPs in
the ALS group was 34.2%, compared with the rate of almost
100% in the PNH group, which was higher in the muscles
without fibs-sw (43.75%) of the ALS patients.
3.3. Comparison of Fasciculations in ALS and PNH. Benign
FPs in the PNH group were with smaller amplitude
(p<0:001), shorter duration (p<0:001), and fewer phases
and turns (p<0:001), when compared with the malignant
FPs in ALS. The area of FPs in the PNH group was signifi-
cantly smaller than that in the ALS group (p<0:001). The
incidence of polyphasic FPs (phases > 4) in ALS was dis-
tinctly greater than PNH (p<0:01). The firing frequency of
FPs repeatedly recorded in the PNH group was higher than
that in the ALS group (Table 2).
A total of 278 FPs were recorded in the normal strength
muscles of ALS, which were divided into two groups (i.e.,
the G1 and G2 groups), according to whether they were
accompanied by the onset of denervation activities. There
was no significant difference in the amplitude, duration,
phases and turns, and area of FPs between the G1 and G2
groups in ALS. However, the proportion of the polyphasic
FPs in the G2 group was significantly higher than that in
the G1 group (p<0:001). However, the amplitude, duration,
phases and turns, area, and polyphasic ratios of FPs in the
010203040
Patient number
4
3
2
1
Body regions
bs-sw
fPs
Figure 6: Comparison of number of involved body regions of fasciculation potentials (FPs) and fibrillations/sharp-waves (fibs-sw) in ALS.
Figure 7: Fasciculations recorded in tibialis anterior muscle in PNH.
7BioMed Research International

normal strength muscles without denervation in the ALS
group (G1) showed the same diversity as those between the
ALS and PNH groups (Table 3).
The number of fasciculations detected in the muscles of
different muscle strength varied greatly. The G2 group with
mild muscle weakness of ALS had the highest number of
FPs, followed by the G1 normal muscle group, and the lowest
number of FPs was observed for the G3 severe muscle weak-
ness group. The mean number of fasciculations (of different
shapes) of each muscle showed the same trend, with the
(a)
(b)
(c)
Figure 8: Fasciculations recorded in ALS. (a) Fasciculations recorded in the biceps (MRC3, fibs-sw 2+) of an ALS patient. (b, c) Fasciculations
recorded in the rectus abdominis (MRC5, fibs-sw 2+) of another ALS patient. The components showing intermittent conduction block and
multifocal triggering were marked by arrows.
8 BioMed Research International

mean shapes of 7.72, 8.67, and 7.03, respectively, for the G1,
G2, and G3 groups, with however no statistically significant
difference (based on Fisher’s exact test). The amplitude of
FPs in the ALS G2 group (MRC4) was higher than those in
the normal and severe weak muscles (for both the G1 and
G3 groups, p<0:05), and the area of FPs in the G2 group
was larger than that in the G1 group (p<0:05). The duration
of FPs in various ALS groups did not differ significantly from
each other nor did the phases and turns of FPs. The percent-
age of polyphasic FPs was higher in the groups of muscles
with normal strength and mild weakness (p<0:001).
Accompanied with the greater FP number in the mild weak
muscle group (G2), the FP firing frequency of the G2 group
was higher than that in the G1 group, which was the lowest
in the G3 group, with however no statistically significant dif-
ference (Table 4).
4. Discussion
In this study, the whole detection rate of FPs in the ALS
patients with the needle EMG was 45.1%, which was signifi-
cantly lower than the detection rate with ultrasound (74%)
[9]. Indeed, the application of the needle EMG examination
has been limited by the detection range of the concentric
Table 2: Parameters of fasciculation potentials (FPs) in ALS and PNH.
Number of FPs ALS FPs PNH FPs p
783 183
Amplitude (μV) 508.00 (85-6080) 333.00 (90-2300) p≤0:001
Duration (ms) 15.73 (0.9-30) 13.56 (4.7-27.0) p≤0:001
Number of phases 4.32 (1-16) 3.39 (1-9) p≤0:001
Number of turns 4.25 (0-22) 2.73 (0-10) p≤0:001
Area (mVms) 0.994 (0.1-25.6) 0.49 (0.1-5.2) p≤0:001
Polyphasic (%) 48.15 26.23 p≤0:001
FP frequency (Hz) 3.02 (0.3-20.0) 7.15 (5.5-40.0) 0.002
The data were shown as the median (range). ALS: amyotrophic lateral sclerosis; PNH: peripheral nerve hyperexcitability syndrome; MRC: medical research
council.
Table 3: Parameters of fasciculation potentials (FPs) in ALS with MRC5 and PNH.
Number of FPs
G1
ALS-MRC 5 without
partial denervation
G2
ALS-MRC 5 with partial
denervation
G3
PNH FPs p
149 129 183
Amplitude (μV) 477.50 (95-4681) 423.00 (85-4998) 333.00 (90-2300)
G1 vs. G3, p≤0:001
G2 vs. G3, p≤0:001
G1 vs. G2, 0.549
Duration (ms) 16.4 (6.3-27.7) 15.48 (5.6-25.6) 13.56 (4.7-27.0)
G1 vs. G3, 0.002
G2 vs. G3, 0.004
G1 vs. G2, 0.740
Number of phases 4.3 (1-10) 4.37 (2-16) 3.39 (1-9)
G1 vs. G3, p≤0:001
G2 vs. G3, p≤0:001
G1 vs. G2, 0.874
Number of turns 3.91 (0-15) 4.41 (0-16) 2.73 (0-10)
G1 vs. G3, p≤0:001
G2 vs. G3, p≤0:001
G1 vs. G2, 0.424
Area (mVms) 0.96 (0.1-13.5) 0.95 (0.1-11.0) 0.49 (0.1-5.2)
G1 vs. G3, p≤0:001
G2 vs. G3, p≤0:001
G1 vs. G2, 0.741
Polyphasic (%) 46.98 51.94 26.23
G1 vs. G3, p≤0:001
G2 vs. G3, p≤0:001
G1 vs. G2, p≤0:001
FP frequency (Hz) 2.50 (0.5-7.8) 2.88 (1.0-8.3) 7.15 (5.5-40.0)
G1 vs. G3, 0.008
G2 vs. G3, 0.002
G1 vs. G2, 0.681
The data were shown as the median (range). ALS: amyotrophic lateral sclerosis; PNH: peripheral nerve hyperexcitability syndrome; MRC: medical research
council.
9BioMed Research International

needle electrodes. Regensburger et al. [11] have reported that
the mean detection radius of EMG for the fasciculations was
7.75 mm, comparable to a motor unit size. However, consid-
ering the irreplaceable importance of needle EMG in the
detection of neurogenic defects, combined with the signifi-
cance of FPs as the denervated potential in the electrophysi-
ological diagnosis of ALS, it is necessary to detect and identify
the FPs in the thoracic and bulbar regions of patients, where
the denervated potentials are difficult to detect accurately. In
this study, we routinely examined the lingual and sternoclei-
domastoid muscles of the medulla oblongata segment, para-
vertebral muscles, and rectus abdominis of the thoracic
segment of ALS patient. The sensitivities of the detection
for neurogenic deficiency associated with combined FPs
and fibs-sw were increased to 67.8% and 96.6% in the bulbar
and thoracic regions, higher than those of the ultrasonic
detection of a single muscle in these regions [9, 12].
It is difficult to distinguish ALS from PNH by examining
the FP detection rate in the muscles of a particular body
region of the patient. Our results showed that the FP detec-
tion rate in the PNH group (53.2%) was higher than that in
the ALS group. The patients in the PNH group could be
divided into two groups (i.e., the groups with disease dura-
tions less or more than 6 months), and the mean detection
Table 4: Parameters of fasciculation potentials (FPs) in ALS with different muscle strength and PNH.
Number of FPs
G1
ALS-MRC 5
G2
ALS-MRC 4
G3
ALS-MRC 3
G4
PNH FPs p
278 373 132 183
Amplitude (μV) 445.00 (85-4998) 572.00 (89-4681) 445.50 (40-6080) 333.00 (90-2300)
G1 vs. G4, p≤0:001
G2 vs. G4, p≤0:001
G3 vs. G4, p≤0:001
G1 vs. G2, 0.001
G1 vs. G3, 0.912
G2 vs. G3, 0.006
Duration (ms) 15.73 (5.6-27.7) 15.63 (9-15.0) 16.35 (7.8-27.0) 13.56 (4.7-27.0)
G1 vs. G4, p≤0:001
G2 vs. G4, p≤0:001
G3 vs. G4, p≤0:001
G1 vs. G2, 0.639
G1 vs. G3, 0.243
G2 vs. G3, 0.277
Number of phases 4.34 (1-16) 4.35 (1-16) 4.18 (2-14) 3.39 (1-9)
G1 vs. G4, p≤0:001
G2 vs. G4, p≤0:001
G3 vs. G4, p≤0:001
G1 vs. G2, 0.827
G1 vs. G3, 0.675
G2 vs. G3, 0.529
Number of turns 4.15 (0-16) 4.47 (0-22) 3.90 (1-13) 2.73 (0-10)
G1 vs. G4, p≤0:001
G2 vs. G4, p≤0:001
G3 vs. G4, p≤0:001
G1 vs. G2, 0.128
G1 vs. G3, 0.610
G2 vs. G3, 0.066
Area (mVms) 0.96 (0.1-13.5) 1.04 (0.1-13.3) 0.96 (0.1-25.6) 0.49 (0.1-5.2)
G1 vs. G4, p≤0:001
G2 vs. G4, p≤0:001
G3 vs. G4, p≤0:001
G1 vs. G2, 0.034
G1 vs. G3, 0.333
G2 vs. G3, 0.478
Polyphasic (%) 49.28 48.79 43.94 26.23
G1 vs. G4, p≤0:001
G2 vs. G4, p≤0:001
G3 vs. G4, p≤0:001
G1 vs. G2, p≤0:001
G1 vs. G3, p≤0:001
G2 vs. G3, p≤0:001
FP frequency (Hz) 2.88 (0.5-8.3) 3.60 (0.5-12.5) 1.20 (0.3-20.0) 7.15 (5.5-40.0)
G1 vs. G4, 0.001
G2 vs. G4, 0.004
G3 vs. G4, 0.018
G1 vs. G2, 0.356
G1 vs. G3, 0.542
G2 vs. G3, 0.452
The data were shown as median (range). ALS: amyotrophic lateral sclerosis; PNH: peripheral nerve hyperexcitability syndrome; MRC: medical research council.
10 BioMed Research International

rates of FPs in these two groups were 70.47% and 47.5%,
respectively, with no statistical differences in PNH between
these two groups. The detection rates were both higher
than those in the ALS patients. However, patients with
PNH tended to be associated with a tremor in the extrem-
ities and gluteal muscle symptoms (especially the patients
with subacute onset), where the FPs companied with neu-
romyotonic and myokymic discharges would be easily
detected and the fasciculations in two sides of the tongue
were rarely observed.
The FPs in ALS were generally more complex than those
in PNH. In this study, our results showed that there were sig-
nificant differences in the amplitude, duration, phases, and
turns and area of FPs between these two groups. Although
the polyphasic FP proportion of the PNH group was signifi-
cantly lower than that of the ALS group, it was still higher
when compared with the previous findings [13]. Several
influencing factors should be also considered. Firstly, two
patients with hypokalemia in the PNH group had propor-
tions of polyphasic FPs up to 45%-50% according to the ret-
rospective study. Considering the acute onset of muscle
twitches, spasm and normal serum creatine enzyme levels,
the FPs detected in those two patients were not excluded.
In one of these two patients, the typical after-discharge
potentials were observed during the motor nerve conduction
test, and neither neurogenic nor myogenic MUPs were
observed during the weak effort analysis, for both of these
two patients. Kuwabara and Misawa [14] have found that
the axons of motor nerve became substantially hyperpolar-
ized in the patient with hypokalemia. Therefore, we suggest
that the hypokalemia and transient muscle weakness are
merely companying symptoms, which might be due to the
expression of related antibodies in the kidney [15]. However,
the minor muscle damages that could not be detected by nee-
dle EMG could not be excluded, which may be one of the rea-
sons for the increased polyphasic FP ratio.
de Carvalho and Swash [13] have revealed that the FPs in
the ALS patient muscles show no reinnervation (the earliest
stage of that muscle), which are similar with FPs in the BFS
in size, duration, and morphology. In this study, our results
showed the FPs recorded in the muscles with normal
strength, and no fibs-sw were of significantly higher ampli-
tude, longer duration, and increased number of phases, com-
pared with the FPs in the PNH group. However, the MUP
morphology of different muscles was not quantitatively ana-
lyzed, and it was possible that the FPs with more complex
morphology and longer duration were accompanied by the
neurogenic changes of MUPs in the muscles with normal
strength and no fibs-sw [16]. In addition, these results sup-
ported the findings from Krarup [16], showing that, in 44%
of muscles in the ALS patients, the neurogenic MUPs
occurred in the absence of the denervation activity. Our
results showed that, in patients with ALS, the FPs with the
normal morphology appear first, followed by the FPs with
more complex patterns and the subsequent occurrence of
denervation activity (fibs-sw), which were in line with the
findings from de Carvalho and Swash [13]. If combined with
the pathological evolution of patients with ALS, the fibs-sw
would not disappear, once it appeared during the short-
medium electrophysiological follow-up. In general, the ear-
lier the course of ALS, the more difficult it is to detect the
denervation potentials, while the more progressed the disease
course, the more difficult it is to detect the fasciculation
potentials.
5. Conclusion
In summary, our results showed that the firing frequencies of
FPs with the same morphology were higher in the PNH
group than in the ALS group, which was contrary to some
previous findings [9]. However, further studies are still
needed to verify whether the FPs detected at the same site
had the same shape on the needle EMG. In addition, the
number of included patients was limited, especially for the
ALS group with lower limb and bulbar-onset. Only 2 patients
had thoracic-onset in our ALS patient group. This had
impact on results, as statistical comparisons of FP detection
rates between groups defined by region-of-onset lacks the
reliability. Thus, further in-depth studies are still needed,
with enlarged sample sizes and exclusion screening for the
PNH patients.
Data Availability
The data that support the findings of this study are available
on request from the corresponding author.
Conflicts of Interest
The authors declare that there is no conflict of interest
regarding the publication of this paper.
Authors’Contributions
Hua Wang and Bin Liu contributed equally to this work.
References
[1] M. de Carvalho, M. C. Kiernan, and M. Swash, “Fasciculation
in amyotrophic lateral sclerosis: origin and pathophysiological
relevance,”Journal of Neurology, Neurosurgery, and Psychia-
try, vol. 88, no. 9, pp. 773–779, 2017.
[2] D. D. Mitsikostas, N. Karandreas, P. Coutsopetras, P. Piperos,
C. Lygidakis, and C. Papageorgiou, “Fasciculation potentials in
healthy people,”Muscle & Nerve, vol. 21, no. 4, pp. 533–535,
1998.
[3] A. Ahmed and Z. Simmons, “Isaacs syndrome: a review,”Mus-
cle & Nerve, vol. 52, no. 1, pp. 5–12, 2015.
[4] K. Sawlani and B. Katirji, “Peripheral nerve hyperexcitability
syndromes,”Continuum, vol. 23, pp. 1437–1450, 2017.
[5] M. O. Santos, M. Swash, and M. de Carvalho, “The generator
site in acquired autoimmune neuromyotonia,”Clinical Neuro-
physiology, vol. 128, no. 4, pp. 643–646, 2017.
[6] M. de Carvalho, R. Dengler, A. Eisen et al., “Electrodiagnostic
criteria for diagnosis of ALS,”Clinical Neurophysiology,
vol. 119, no. 3, pp. 497–503, 2008.
[7] K. R. Mills, “Characteristics of fasciculations in amyotrophic
lateral sclerosis and the benign fasciculation syndrome,”Brain,
vol. 133, no. 11, pp. 3458–3469, 2010.
11BioMed Research International

[8] M. de Carvalho and M. Swash, “Fasciculation potentials: a
study of amyotrophic lateral sclerosis and other neurogenic
disorders,”Muscle & Nerve, vol. 21, no. 3, pp. 336–344, 1998.
[9] Y. I. Noto, N. G. Simon, A. Selby et al., “Ectopic impulse gen-
eration in peripheral nerve hyperexcitability syndromes and
amyotrophic lateral sclerosis,”Clinical Neurophysiology,
vol. 129, no. 5, pp. 974–980, 2018.
[10] B. R. Brooks, “El Escorial World Federation of Neurology cri-
teria for the diagnosis of amyotrophic lateral sclerosis. Sub-
committee on Motor Neuron Diseases/Amyotrophic Lateral
Sclerosis of the World Federation of Neurology Research
Group on Neuromuscular Diseases and the El Escorial "Clini-
cal limits of amyotrophic lateral sclerosis" workshop contribu-
tors,”Journal of the neurological sciences, vol. 124, 1994.
[11] M. Regensburger, F. Tenner, C. Möbius, and A. Schramm,
“Detection radius of EMG for fasciculations: empiric study
combining ultrasonography and electromyography,”Clinical
Neurophysiology, vol. 129, no. 2, pp. 487–493, 2018.
[12] Y. Tsuji, Y. I. Noto, K. Shiga, S. Teramukai, M. Nakagawa, and
T. Mizuno, “A muscle ultrasound score in the diagnosis of
amyotrophic lateral sclerosis,”Clinical Neurophysiology,
vol. 128, no. 6, pp. 1069–1074, 2017.
[13] M. de Carvalho and M. Swash, “Fasciculation potentials and
earliest changes in motor unit physiology in ALS,”Journal of
Neurology, Neurosurgery, and Psychiatry, vol. 84, no. 9,
pp. 963–968, 2013.
[14] S. Kuwabara and S. Misawa, “Axonal ionic pathophysiology in
human peripheral neuropathy and motor neuron disease,”
Current Neurovascular Research, vol. 1, no. 4, pp. 373–379,
2004.
[15] M. Lai, M. G. Huijbers, E. Lancaster et al., “Investigation of
LGI1 as the antigen in limbic encephalitis previously attributed
to potassium channels: a case series,”Lancet Neurology, vol. 9,
no. 8, pp. 776–785, 2010.
[16] C. Krarup, “Lower motor neuron involvement examined by
quantitative electromyography in amyotrophic lateral sclero-
sis,”Clinical Neurophysiology, vol. 122, no. 2, pp. 414–422,
2011.
12 BioMed Research International