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Amplitude of sensory nerve action potential in early stage diabetic peripheral neuropathy: An analysis of 500 cases

Authors:

Abstract

Early diagnosis of diabetic peripheral neuropathy is important for the successful treatment of diabetes mellitus. In the present study, we recruited 500 diabetic patients from the Fourth Affiliated Hospital of Kunming Medical University in China from June 2008 to September 2013: 221 cases showed symptoms of peripheral neuropathy (symptomatic group) and 279 cases had no symptoms of peripheral impairment (asymptomatic group). One hundred healthy control subjects were also recruited. Nerve conduction studies revealed that distal motor latency was longer, sensory nerve conduction velocity was slower, and sensory nerve action potential and amplitude of compound muscle action potential were significantly lower in the median, ulnar, posterior tibial and common peroneal nerve in the diabetic groups compared with control subjects. Moreover, the alterations were more obvious in patients with symptoms of peripheral neuropathy. Of the 500 diabetic patients, neural conduction abnormalities were detected in 358 cases (71.6%), among which impairment of the common peroneal nerve was most prominent. Sensory nerve abnormality was more obvious than motor nerve abnormality in the diabetic groups. The amplitude of sensory nerve action potential was the most sensitive measure of peripheral neuropathy. Our results reveal that varying degrees of nerve conduction changes are present in the early, asymptomatic stage of diabetic peripheral neuropathy.
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NEURAL REGENERATION RESEARCH
July 2014,Volume 9,Issue 14 www.nrronline.org
Amplitude of sensory nerve action potential in early
stage diabetic peripheral neuropathy: an analysis of
500 cases
1 Department of Neurology, the Fourth Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China
2 Neuroscience Institute, Kunming Medical University, Kunming, Yunnan Province, China
Yunqian Zhang and Jintao Li
contributed equally to this work.
Corresponding author:
Jianlin Wang, M.D., Department of
Neurology, the Fourth Affiliated Hospital
of Kunming Medical University, Kunming
650021, Yunnan Province, China,
2605691027@qq.com.
doi:10.4103/1673-5374.137593
http://www.nrronline.org/
Accepted: 2014-04-29
Yunqian Zhang1, Jintao Li2, Tingjuan Wang1, Jianlin Wang1
Introduction
Diabetic peripheral neuropathy is the most common chronic
complication of diabetes mellitus, with an incidence rate of
about 50 % (Shi et al., 2013; Galuppo et al., 2014; O’Brien
and Karem, 2014; Won et al., 2014; Zhong et al., 2014).
Once symptoms appear, there are few effective therapeu-
tic strategies (Won et al., 2014). Therefore, early discovery
and diagnosis are extremely important. Nerve conduction
studies are the most common method for diagnosis of pe-
ripheral neuropathy (An et al., 2007; Kincaid et al., 2007;
Koçer et al., 2007; Severinsen and Andersen, 2007; Kiziltan
and Benbir, 2008; Løseth et al., 2008, 2010; Uluc et al., 2008;
Asad et al., 2009; Hemmi et al., 2009; Watanabe et al., 2009;
Charles et al., 2010; Dyck et al., 2010; Lee et al., 2010; Suh
et al., 2010; Watanabe et al., 2010; Altun et al., 2011; Dyck
et al., 2011; Koytak et al., 2011; Shin et al., 2011; Heise et al.,
2012; Mondal et al., 2012; Morimoto et al., 2012; Spadella et
al., 2012; Arimura et al., 2013; Joa and Kim, 2013; Koo et al.,
2013; Richardson et al., 2013; Chiles et al., 2014; McLellan
et al., 2014). Heise et al. (2012) found that the combined i
n-
dex, comprising five parameters of nerve conduction, had
greater sensitivity and equivalent specificity compared with
individual parameters in the detection of diabetic polyneu-
ropathy. In another study, Erdoğan et al. (2011) found that
the strength-duration time constant may be useful in the
early stages of neuropathy, since most patients with diabetic
neuropathy had predominant changes in this parameter in
their lower extremities. In our previous electrophysiology
studies, we used several indices that are routinely measured
in diabetic and suspected diabetic patients, with the aim of
facilitating early diagnosis of diabetic peripheral neurop-
athy, reducing treatment costs and improving therapeutic
success. In the present study, we sought to establish a sensi-
tive index for nerve conduction studies in the early diagno-
sis of peripheral neuropathy in 500 patients with diabetes
mellitus.
Subjects and Methods
Subjects
500 diabetic patients who visited the doctor’s office in the
Abstract
Early diagnosis of diabetic peripheral neuropathy is important for the successful treatment of
diabetes mellitus. In the present study, we recruited 500 diabetic patients from the Fourth Affil-
iated Hospital of Kunming Medical University in China from June 2008 to September 2013: 221
cases showed symptoms of peripheral neuropathy (symptomatic group) and 279 cases had no
symptoms of peripheral impairment (asymptomatic group). One hundred healthy control sub-
jects were also recruited. Nerve conduction studies revealed that distal motor latency was longer,
sensory nerve conduction velocity was slower, and sensory nerve action potential and amplitude
of compound muscle action potential were significantly lower in the median, ulnar, posterior
tibial and common peroneal nerve in the diabetic groups compared with control subjects. More-
over, the alterations were more obvious in patients with symptoms of peripheral neuropathy. Of
the 500 diabetic patients, neural conduction abnormalities were detected in 358 cases (71.6%),
among which impairment of the common peroneal nerve was most prominent. Sensory nerve
abnormality was more obvious than motor nerve abnormality in the diabetic groups. The ampli-
tude of sensory nerve action potential was the most sensitive measure of peripheral neuropathy.
Our results reveal that varying degrees of nerve conduction changes are present in the early, as-
ymptomatic stage of diabetic peripheral neuropathy.
Key Words: nerve regeneration; peripheral nerve injury; diabetic peripheral neuropathy; neural con-
duction; electrophysiology; sensory nerve; motor nerve; early diagnosis; neural regeneration
Funding: This work is supported by the Science and Research Fund of Academic Department in
Yunnan Province in China, No. 2011C08.
Zhang YQ, Li JT, Wang TJ, Wang JL. Amplitude of sensory nerve action potential in early stage dia-
betic peripheral neuropathy: an analysis of 500 cases. Neural Regen Res. 2014;9(14):1389-1394.
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Zhang YQ, et al. / Neural Regeneration Research. 2014;9(14):1389-1394.
Fourth Affiliated Hospital of Kunming Medical University in
China from June 2008 to November 2013 were recruited by
advertisement. All patients’ conditions were consistent with
the diagnostic criteria for diabetes, approved by the World
Health Organization (Wendland et al., 2012). One hundred
healthy control subjects who went to the doctor’s office for
other medical reasons were also recruited. Exclusion criteria:
(1) peripheral neuropathy due to severe liver and kidney
diseases, nutrition deficiency, connective tissue diseases and
other metabolic or hereditary diseases; (2) radiculopathy
due to cervical spondylosis and lumbar intervertebral disc
protrusion; (3) history of long-term alcohol consumption
or prolonged contact with poisonous substances (such as
heavy metals) that could result in peripheral impairment;
(4) history of drugs (such as isoniazid and furaxone) that
may affect neural function. According to the symptoms
of peripheral nerve impairment (such as numbness, pain,
weakness, or burning cooling sensations in the limbs), the
diabetic patients were divided into two groups, symptomatic
and asymptomatic. One hundred healthy control subjects
were also recruited by advertisement. There were no signifi-
cant differences in disease course between the two groups of
patients with diabetes, and no significant differences in gen-
der, age, body height or weight among all three experimental
groups (P > 0.05; Table 1).
The procedures were in accordance with institutional and
regional ethical standards of responsible experimentation
and with the Helsinki Declaration of 1975. The Chinese Eth-
ics Committee approved the age range of adult research par-
ticipants and obtained consent for children aged over 7 years
participating in the trial. Subject approval was obtained for
the electrophysiological test procedures, which were in accor-
dance with the guidelines of the Chinese Ethics Committee.
Analysis of neural conduction
Each subject lay on a bed in a quiet room (22–25°C) with
limbs relaxed. Skin temperature was maintained above 32°C.
Electromyography/evoked potential apparatus (Dantec
Dynamics, Skovlunde, Denmark) was employed in nerve
conduction studies. Motor and sensory nerve conduction of
unilateral or bilateral median nerve, ulnar nerve, posterior
tibial nerve and common peroneal nerve were measured
separately. In the motor nerve conduction test, the sellar
stimulus electrode was placed in front of the stylomastoid
foramen, with the negative pole of the electrode placed at
the distal end of the nerve. The surface electrode was placed
at the proximal end of the nerve, on the muscle belly of the
frontalis, nasalis or orbicularis oris muscles. The groundwire
was placed between the stimulus and recording electrodes.
For sensory nerve conduction tests, a ring electrode was
placed around the end of the fingers or toes, that is, the dis-
tal end of the sensory nerve, and used to stimulate the me-
dian, ulnar and posterior tibial nerves. A surface electrode
was employed to stimulate the common peroneal nerve.
The recording electrode was placed at the proximal end of
the spinal cord using the antegrade method, described pre-
viously (Cui, 2006). Detection parameters were: amplitude
of compound motor action potential, distal motor latency,
amplitude of sensory nerve action potential, and sensory
nerve conduction velocity. Control values corresponded to
the standards of electromyography for age and gender in Pe-
king Union Medical College Hospital in China (Zhang et al.,
2013).
Statistical analysis
Data were analyzed using SPSS 11.5 software (SPSS, Chica-
go, IL, USA) and presented as mean ± SD. Paired t-tests were
used to compare measurement data. Numeration data are
expressed as numbers of nerve fibers (%). A chi-square test
was used to compare rates between two samples. P < 0.05
was considered statistically significant (We used analysis of
variance to compare the data of two experimental groups
and control, and got similar outcome to those of paired
t-tests, so we adopted the results of t-test as the final statisti-
cal outcome).
Results
Motor and sensory nerve conduction in patients with
diabetic peripheral neuropathy
Distal latency of motor nerve conduction in the median, ul-
nar, posterior tibial and common peroneal nerve was longer
in the asymptomatic diabetic group than in healthy controls,
and the amplitude of compound motor action potential was
significantly lower compared with that of the control group
(P < 0.05; Figure 1A). Distal motor latency in the median
and common peroneal nerves in the symptomatic group
was markedly longer than in the asymptomatic group, and
compound motor action potential amplitude in the median
and common peroneal nerve was significantly lower in the
symptomatic group than in asymptomatic patients (P < 0.05;
Figure 1B).
Similarly to the sensory nerve conduction comparison
in the median, ulnar, posterior tibial and common pero-
neal nerve, sensory nerve action potential amplitude and
Table 1 Demographic information of diabetic patients and control subjects
Item
Diabetic patients
Control subjects
Asymptomatic group Symptomatic group
n279 221 100
Gender (n, male/female) 151/128 115/106 48/52
Age (year) 62.3±8.8(34–87) 64.8±9.0(37–89) 61.1±10.8(32–78)
Course of disease (year) 7.7(0.8–18) 8.1(0.1–21)
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sensory nerve conduction velocity in both diabetic groups
was significantly lower than in healthy controls (P < 0.05).
Importantly, sensory nerve action potential amplitude and
sensory nerve conduction velocity of the median, ulnar, pos-
terior tibial and common peroneal nerves in the symptom-
atic group was significantly lower than in the asymptomatic
group (P < 0.05; Figure 2).
Outcome analysis of nerve conduction studies
Of 500 diabetic patients, 358 (71.6%) exhibited nerve con-
duction abnormalities. The highest rate of abnormality was
found in the common peroneal nerve, followed by the pos-
terior tibial nerve and median nerve, with the ulnar nerve
showing the lowest rate of abnormality (P < 0.05). In the
motor nerve conduction tests, the common peroneal nerve
showed the highest rate of absent waveforms, whereas in
sensory nerve conduction tests, the posterior tibial nerve
was found to have the highest rate of absent waveforms. The
most sensitive index for nerve conduction studies in diabet-
ic patients was sensory nerve action potential, followed by
Figure 1 Motor nerve conduction in diabetic patients with/without peripheral neuropathy and in control subjects.
(A) Distal motor latency (DML); (B) compound muscle action potential (CMAP). Data are presented as mean ± SD. *P < 0.05, vs. NC; #P < 0.05,
vs. ASG (paired t-test). SG: Symptomatic group (n = 221); ASG: asymptomatic group (n = 279); NC: normal control group (n = 100).
Figure 2 Sensory nerve conduction in diabetic patients with/without peripheral neuropathy and in control subjects.
(A) Sensory nerve conduction velocity (SCV); (B) sensory nerve action potential (SNAP). Data are presented as mean ± SD. *P < 0.05, vs. NC; #P <
0.05, vs. ASG (paired t-test). SG: Symptomatic group (n = 221); ASG: asymptomatic group (n = 279); NC: normal control group (n = 100).
Table 2 Abnormal distribution (%) of motor and sensory nerve conduction in diabetic patients with/without peripheral neuropathy and in
control subjects
Nerve Number of nerve fibers Total abnormality
Motor nerve conduction Sensory nerve conduction
χ2P
No wave DML CMAP No wave SCV SNAP
Median 972 52.9 0.3 16.4 13.0 10.6 32.9 42.3 281.006 < 0.05
Ulnar 953 34.5 0 1.8 2.1 0.9 2.9 33.6 334.908 < 0.05
Tibial 912 53.3 0.5 1.1 1.3 28.8 17.8 24.5 603.809 < 0.05
Peroneal 908 60.0 1.8 11.6 21.8 23.7 22.0 36.3 248.002 < 0.05
If amplitude and conductive velocity abnormalities occurred simultaneously in one nerve, one nerve conductive abnormality was counted. A chi-
square test was used for comparison between two samples. DML: Distal motor latency; CMAP: compound motor action potential; SCV: sensory
nerve conduction velocity; SNAP: sensory nerve action potential.
A
DML (ms)
CMAP (mV)
Median Median
*#
*# *#
*#
*#
*#
*
*
*
*
*
*
*
***
SG SGASG ASGNC NC
Ulnar UlnarTibial TibialPeroneal Peroneal
6.0
5.0
4.0
3.0
2.0
1.0
0
25
20
15
10
5
0
B
A
SCV (m/s)
SNAP (mV)
Median Median
*#
*#
*#
*#
*#
*#
*#
*#
*
*
*
*
*
*
*
*
SG SGASG ASGNC NC
Ulnar UlnarTibial TibialPeroneal Peroneal
70
60
50
40
30
20
10
0
35
30
25
20
15
10
5
0
B
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Zhang YQ, et al. / Neural Regeneration Research. 2014;9(14):1389-1394.
sensory nerve conduction velocity; compound motor action
potential and distal motor latency had relatively low sensi-
tivity. Among the nerve conduction indices, the highest rate
of abnormality was found in median nerve sensory nerve
action potential (Table 2).
Discussion
Diabetic peripheral neuropathy commonly develops insidi-
ously, with various clinical manifestations. In the early stages,
diagnosis is difficult as there are no symptoms. Fortunately,
increasing use of electrophysiological techniques that allow
the identification of sub-clinical pathological changes has
made early diagnosis of diabetic peripheral neuropathy pos-
sible (Liu et al., 2005; Al-Geffari, 2012; Balbinot et al., 2012;
Barriga et al., 2012; Gulichsen et al., 2012; Kuntzer et al.,
2012; Calvet et al., 2013; Fang et al., 2013; Mete et al., 2013;
Papanas et al., 2013; Sellers et al., 2013; Sun et al., 2013; Gor-
don Smith et al., 2014). Electrophysiology has the advantages
of being objective and sensitive, allowing the scope and ex-
tent of affected peripheral nerves to be precisely ascertained
and providing a conclusive diagnosis of diabetic peripheral
neuropathy. Indeed, nerve conduction studies have become
an indispensable tool in the discovery of peripheral nerve
abnormalities. In patients with diabetic peripheral neu-
ropathy, the main abnormality in nerve conduction studies
manifests as reduced amplitude, slowed conductive velocity
or prolonged latent phase, and in severe cases the waveform
is eliminated entirely.
In the present study, we found that the total abnormal
nerve conduction rate in both diabetic groups was 71.6%,
which was in accordance with a previous report (Banthia et
al., 2013). Distal motor latencies in the median, ulnar, poste-
rior tibial and common peroneal nerves in the asymptomat-
ic group were significantly prolonged compared with those
in the control group. Sensory nerve conduction velocity
and amplitudes of sensory nerve action potential and com-
pound motor action potential were all markedly lower in the
asymptomatic group than in controls, suggesting that im-
pairment of sensory and motor axons and the myelin sheath
at the distal end already exists in the early stages of diabetic
peripheral neuropathy, before symptoms emerge. In the
symptomatic group, sensory nerve conduction velocity was
notably slower, distal motor latency in the median and com-
mon peroneal nerves was significantly prolonged and the
amplitude of compound motor action potential was lower
than in the asymptomatic group. These observations indicate
that after symptomatic peripheral nerve impairment emerg-
es in diabetic patients, lesions in the sensory fibers of the
median, ulnar, posterior tibial and common peroneal nerve,
and in the neuraxis and myelin sheath of motor fibers of the
common peroneal nerve, are markedly aggravated compared
with the asymptomatic stage. Importantly, we show for the
first time that in both groups of diabetic patients, sensory
nerves were affected to a greater extent than motor nerves,
indicating that sensory nerves are more vulnerable to dam-
age than motor nerves in diabetic peripheral neuropathy. In
the diabetic groups, posterior tibial and common peroneal
nerve conduction in the lower extremities had a markedly
higher rate of absent waveforms than the median and ulnar
nerves of the upper extremities, implying that the extent of
nerve fiber lesions in the lower extremities is more severe
than that in the upper extremities in diabetic patients. Im-
portantly, we show for the first time that although diabetic
peripheral neuropathy leads to diffuse conductive abnormal-
ity across whole peripheral nerves, the nearer the damage is
to the distal end, the more severe the extent of impairment.
The total rate of abnormality detected in the median, ul-
nar, posterior tibial and common peroneal nerves in diabetic
patients was 60%. The common peroneal nerve was the most
prominently affected. Moreover, among all patients with di-
abetes, the common peroneal nerve showed the highest rate
of absent waveforms, indicating that among the lesioned
peripheral motor nerves in diabetic patients, the common
peroneal nerve was most severely damaged. The posterior
tibial nerve was most severely impaired from the sensory
nerve tests. Comparing all indices of nerve conduction stud-
ies, we found that sensory nerve action potential was the
most sensitive index. In the present study, the median nerve
showed the highest rate of sensory nerve action potential ab-
normality, suggesting that this nerve is the first to be affected
in diabetes. To our knowledge, we are the first to show a
conclusive and simple relationship between peripheral nerve
lesions and electrophysiological indices in different nerves
commonly affected in diabetic peripheral neuropathy. In
practical terms, this will enable earlier diagnosis of the con-
dition.
Liu et al. (2005) studied 700 patients with diabetic periph-
eral neuropathy using nerve conduction studies and found
that the longer the duration of the disease, the greater the
possibility that abnormal electrophysiology will be observed.
The electrophysiological abnormalities observed in the pres-
ent study may be attributed to nutritional and metabolic
disorders resulting from the diabetes itself, leading to im-
pairment of axoplasmic transport in peripheral nerves, pre-
venting distal axons from acquiring sufficient nutrition and
ultimately leading to their degeneration. In a study by Bi et
al. (2008), it was revealed that sensory nerve action potential
amplitude is more sensitive than nerve conduction velocity in
the diagnosis of mild or early diabetic peripheral neuropathy.
Our study confirmed this notion. Importantly, we found that
the abnormal rate of sensory nerve conduction velocity in
diabetic patients was much higher than that of motor nerve
conduction velocity, corresponding with previous studies (Tan
and Tan, 2003; Kles and Bril, 2006; Vinik et al., 2006; Bi et al.,
2008; Charles et al., 2013). These results indicate that nerve
conduction studies should be used as an important index for
the early diagnosis of diabetic peripheral neuropathy.
Taken together, our data demonstrate that various degrees
of peripheral neuropathy occur in both sensory and mo-
tor nerves in the early stages of diabetes, before symptoms
occur. The extent of impairment in the lower extremities is
more severe than that in the upper extremities. Importantly,
the extent of the lesion in sensory nerves is more severe than
that in motor nerves. Symptoms and sensory nerve impair-
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Zhang YQ, et al. / Neural Regeneration Research. 2014;9(14):1389-1394.
ment will worsen with time; therefore, nerve conduction,
especially sensory nerve action potential detection, should
be routinely examined in diabetic patients so that diabetic
peripheral neuropathy can be discovered and treated as early
as possible.
Author contributions: Zhang YQ was responsible for electro-
physiological test. Li JT was responsible for manuscript writing,
revision and trial design. Wang TJ was responsible for experi-
mental collection and statistical analysis. Wang JL was responsi-
ble for trial design, examination and verification of the experi-
mental data, determination of the final draft of this manuscript.
All authors approved the final version of the paper.
Conflicts of interest: None declared.
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... is the Distal motor latency (DML) and Figure 9B is the compound muscle action potential (CMAP) between symptomatic groups (SG), asymptomatic groups (ASG), and control groups (NC). Reproduced from Ref [32] Figure 10A illustrates the sensory nerve conduction velocity and Figure 10B illustrates the sensory nerve action potential between symptomatic groups, asymptomatic groups, and control groups. Reproduced from Ref [32] . ...
... Reproduced from Ref [32] Figure 10A illustrates the sensory nerve conduction velocity and Figure 10B illustrates the sensory nerve action potential between symptomatic groups, asymptomatic groups, and control groups. Reproduced from Ref [32] . Cold plate test data recording template. ...
... Figure 9A is the Distal motor latency (DML) and Figure 9B is the compound muscle action potential (CMAP) between symptomatic groups (SG), asymptomatic groups (ASG), and control groups (NC). Reproduced from Ref [32]. ...
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The growing obesity pandemic has caused diabetes to become one of the world’s leading health concerns. Diabetic individuals often suffer from peripheral neuropathy, which is nerve death that typically starts at the extremities and moves from the skin inward to deeper tissues. This nerve death causes painful symptoms including tingling, stinging, numbness, and others. Current methods to diagnose peripheral neuropathy by measuring nerve function are invasive and painful since they target large axons of the legs; however, by the time the neuropathy reaches the diagnosable axons, it is often too late for intervention. Although no cures for neuropathy are established, aside from analgesics for pain, there are options for mitigating worsening of the disease if diagnosed early enough (for example, glucose control for diabetic neuropathy). There is a critical need for early detection and diagnosis of peripheral neuropathy as obesity and diabetes continue to plague the world. Microneedle fabrication is a growing research area, especially in transdermal drug delivery due to their minimal invasive, pain-free application. The objective of this project is to design a platform using electrically conductive microneedles for early detection of peripheral neuropathy. Using these needles, neurophysiology can be employed to record electrical signal just below the skin to determine the integrity of the nerves to track neuropathy progression. Thus far, prototypes of the device have been tested on mice to establish protocols and understand the hardware and software, with the goal of eventually developing a usable prototype for a longitudinal study of diseased mice and human clinical studies.
... And motor nerve conduction studies are recommended as the new diagnostic gold standard to determine peripheral neuropathy in hand. Studies have shown that sensory and motor nerve changes are present in the early asymptomatic stage of diabetic peripheral neuropathy [9,10]. systematic review and meta-analysis revealed a negative mean difference in grip and pinch strength as well as hand function and dexterity between people with T2DM and healthy controls [11]. ...
... Sensory fibers can be tested using orthodromic conduction (physiological direction) or antidromic conduction (opposite to normal conduction). The sensory nerve conduction study included nerve conduction velocity (m/s), latency (ms), and amplitude (μV) [9,15]. In this study, an orthodromic sensory nerve conduction study was done using EMG diagnostic device. ...
... Although all three nerves show prolongation of latency in the diabetic group, this difference is only significant in the ulnar nerve. The electrophysiological abnormalities may be attributed to nutritional and metabolic disorders resulting from diabetes, this leads to impairment of axoplasmic transport in peripheral nerves, preventing distal axon from acquiring sufficient nutrition and ultimately leading to their degeneration [9]. Kikkawa Y1, Kuwabara S [17] et al 2005 concluded that slowing of nerve conduction presumably caused by metabolic factors, such as decreased Naþ/Kþ-ATPase activity and tissue acidosis. ...
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Aim: The study intends to find out the effect of Type 2 diabetes on the sensory nerve of the upper extremity. Method: This research includes 100 subjects, both male and female, within the age group of 40-80 years. The subjects were divided into two groups, A and B. Where Group A includes 50 subjects which diagnosed type 2 diabetic mellitus. Furthermore, Group B holds 50 normal healthy subjects investigated and normal healthy subjects without diabetes mellitus. Written consent was obtained from the subjects who were ready to be part of this study. Orthodromic sensory nerve conduction studies of median, ulnar, and radial nerve were assessed by using EMG diagnostic device for bilateral upper extremities in both groups. The sensory nerve conduction study included nerve conduction velocity (m/s), latency (ms), and amplitude (μV). The data analyzed using paired 't' test within the group and unpaired 't' test between two groups, using computational statistical software Graph Pad Prism. 'p' value < 0.05 was considered to be statistically significant. Results: The sensory nerve amplitude of all three nerves reduced the velocity of the median & ulnar nerve was reduced and prolonged latency of ulnar nerve in type 2 diabetics as compared to the Non-diabetics group. Conclusion: This study concluded that the type 2 diabetics group has severe sensory nerve affections of the median and ulnar nerve. The therapist should examine the upper extremity of all diabetic subjects, and hand care should be taught to the patients to prevent further complications of diabetic peripheral neuropathy.
... Because of the length-dependent phenomenon, the long nerves in the feet are usually affected in the early stages of polyneuropathy [7,8]. Nerve conduction study (NCS) assessment of the medial plantar and sural (the most distal sensory nerves of the feet) can be used to study the most distal parts of the lower limbs and can be considered a good method for the diagnosis of polyneuropathy in the early stages of diabetes mellitus [9,10]. ...
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... As demonstrated in our study, the increased duration of T2DM revealed a reduced amplitude of sensory and motor nerves (axonopathy) and a decreased motor and sensory nerve velocity due to the loss of fast-conducting axons. Zhang et al. [30] showed that sensory nerves were affected to a greater extent than motor nerves in DN, and the sensory nerve action potential amplitude in the sural nerve was the first abnormality to appear before motor amplitude reduction in peroneal and tibial nerves. Bi et al. [31] demonstrated that amplitude of sensory nerve action potential was a more sensitive parameter than nerve conduction velocity for detecting early diabetic neuropathy. ...
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... [11] The PL deficiency is more widespread among the communities of the Middle East and India. [12,13] The median motor test is one of the most frequently [14,15] conducted tests in electrodiagnosis. It is commonly used in clinical practice. ...
... Quantitative sensory testing, also referred to as nerve conductivity study (NCS) performed via Semmes-Weinstein monofilament (SWM) or pressure-specified sensory device (PSSD), is subjective and influenced by various attributes such as location of damage, body fat, skin surface preparation and does not provide sufficient resolution to detect early onset of polyneuropathy. 3 Although often combined with electromyography (EMG) that uses global response to detect localized defects in a nerve, such NCS technique has poor reproducibility and sensitivity to small structural damage. Imaging methods to detect structural damage in nerve fibers include ultrasound (US) imaging and confocal microscopy. ...
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Diabetic peripheral neuropathy (DPN) is the most common microvascular complication of diabetes that affects approximately half of the diabetic population. Up to 53% of DPN patients experience neuropathic pain, which leads to a reduction in the quality of life and work productivity. Tocotrienols have been shown to possess antioxidant, anti-inflammatory, and neuroprotective properties in preclinical and clinical studies. This study aimed to investigate the effects of tocotrienol-rich vitamin E (Tocovid SuprabioTM) on nerve conduction parameters and serum biomarkers among patients with type 2 diabetes mellitus (T2DM). A total of 88 patients were randomized to receive 200 mg of Tocovid twice daily, or a matching placebo for 12 months. Fasting blood samples were collected for measurements of HbA1c, renal profile, lipid profile, and biomarkers. A nerve conduction study (NCS) was performed on all patients at baseline and subsequently at 2, 6, 12 months. Patients were reassessed after 6 months of washout. After 12 months of supplementation, patients in the Tocovid group exhibited highly significant improvements in conduction velocity (CV) of both median and sural sensory nerves as compared to those in the placebo group. The between-intervention-group differences (treatment effects) in CV were 1.60 m/s (95% CI: 0.70, 2.40) for the median nerve and 2.10 m/s (95% CI: 1.50, 2.90) for the sural nerve. A significant difference in peak velocity (PV) was also observed in the sural nerve (2.10 m/s; 95% CI: 1.00, 3.20) after 12 months. Significant improvements in CV were only observed up to 6 months in the tibial motor nerve, 1.30 m/s (95% CI: 0.60, 2.20). There were no significant changes in serum biomarkers, transforming growth factor beta-1 (TGFβ-1), or vascular endothelial growth factor A (VEGF-A). After 6 months of washout, there were no significant differences from baseline between groups in nerve conduction parameters of all three nerves. Tocovid at 400 mg/day significantly improve tibial motor nerve CV up to 6 months, but median and sural sensory nerve CV in up to 12 months of supplementation. All improvements diminished after 6 months of washout.
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We report a minimally invasive, synaptic transistor-based construct to monitor in vivo neuronal activity via a longitudinal study in mice and use depolarization time from measured data to predict the onset of polyneuropathy. The synaptic transistor is a three-terminal device in which ionic coupling between pre- and post-synaptic electrodes provides a framework for sensing low-power (sub μW) and high-bandwidth (0.1–0.5 kHz) ionic currents. A validated first principles-based approach is discussed to demonstrate the significance of this sensing framework and we introduce a metric, referred to as synaptic efficiency to quantify structural and functional properties of the electrodes in sensing. The application of this framework for in vivo neuronal sensing requires a post-synaptic electrode and its reference electrode and the tissue becomes the pre-synaptic signal. The ionic coupling resembles axo-axonic junction and hence we refer to this framework as an ad hoc synaptic junction. We demonstrate that this arrangement can be applied to measure excitability of sciatic nerves due to a stimulation of the footpad in cohorts of m+/db and db/db mice for detecting loss in sensitivity and onset of polyneuropathy. The signal attributes were subsequently integrated with machine learning-based framework to identify the probability of polyneuropathy and to detect the onset of diabetic polyneuropathy.
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Background: Diabetic peripheral neuropathy (DPN) is an essential precursor leading to diabetic limb loss. Neurologic screening tests, including the 128-Hz tuning fork (TF), have long been used to identify and track the progression of DPN, thereby guiding the implementation of preventive strategies. Although a sensitive indicator of neuropathy, shortcomings of TF testing include the lack of standardization and quantification of clinical findings. In an attempt to overcome these limitations, a novel 128-Hz electronic TF (ETF) prototype has been developed that is capable of performing accurate timed vibration tests (TVTs). This study was designed to assess the ability of the ETF to detect sensory impairment compared with three established neurologic screening methods: the Semmes-Weinstein monofilament test, the biothesiometer, and the sharp/dull discrimination test. Methods: Fifty-five test patients were recruited from the primary author's practice and enrolled according to an approved protocol. The 10-g Semmes-Weinstein monofilament test and the sharp/dull discrimination test were administered in standard fashion to the plantar aspects of digits 1 and 5 bilaterally. The ETF and the biothesiometer (25-V setting) were applied to the dorsal aspects of the distal phalanx of the hallux and fifth metatarsal head bilaterally. Results: The sensitivity and specificity of neuropathy detection for the ETF were 0.953 and 0.761, respectively, using conventional tests as reference standards. Conclusions: Performance of TVTs with the ETF detected sensory impairment compared with three conventional neurologic screening methods. Given these findings, the ETF could facilitate the use of standardized TVTs as an indicator of DPN progression.
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Clinical trials have demonstrated that it is possible to prevent diabetes through lifestyle modification, pharmacological intervention, and surgery. This review aims to summarize the effectiveness of these various therapeutic interventions in reducing the risk of progression of prediabetes to diabetes, and address the challenges to implement a diabetes prevention program at a community level. Strategies focusing on intensive lifestyle changes are not only efficient but cost-effective and/or cost-saving. Indeed, lifestyle intervention in people at high risk for type 2 diabetes mellitus (T2DM) has been successful in achieving sustained behavioral changes and a reduction in diabetes incidence even after the counseling is stopped. Although prediabetes is associated with health and economic burdens, it has not been adequately addressed by interventions or regulatory agencies in terms of prevention or disease management. Lifestyle intervention strategies to prevent T2DM should be distinct for different populations around the globe and should emphasize sex, age, ethnicity, and cultural and geographical considerations to be feasible and to promote better compliance. The translation of diabetes prevention research at a population level, especially finding the most effective methods of preventing T2DM in various societies and cultural settings remains challenging, but must be accomplished to stop this worldwide epidemic.
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Diabetic peripheral neuropathy (DPN) is the most common complication associated with diabetes. DPN can present as a loss of sensation, may lead to neuropathic ulcers, and is a leading cause of amputation. Reported estimates of the prevalence of DPN vary due to differences in study populations and diagnostic criteria. Furthermore, the epidemiology and clinical characteristics of DPN in Korean patients with type 2 diabetes mellitus (T2DM) are not as well understood as those of other complications of diabetes such as retinal and renal disease. Recently, the Diabetic Neuropathy Study Group of the Korean Diabetes Association (KDA) conducted a study investigating the impact of DPN on disease burden and quality of life in patients with T2DM and has published some data that are representative of the nation. This review investigated the prevalence and associated clinical implications of DPN in Korean patients with diabetes based on the KDA study.
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Nephropathy, retinopathy cardiomyopathy and peripheral neuropathy are all recognized as important complications in about 50% of diabetes mellitus (DM) patients, mostly related to a poor glycemic control or to an improper management of this pathology. In any case, amongst others, diabetic peripheral neuropathy (DPN) seems the leading and most painful complication usually affecting many DM patients. For this reason, this work was conceived to review the large variety of strategies adopted for management of DPN, starting from the most conventional therapies to arrive at alternative approaches. From this perspective, both the most popular pharmacological treatments used to respond to the poorly effect of common analgesics-non-steroidal anti-inflammatory drugs (NSAIDS) and opioids-understood as gabapentin vs. pregabalin clinical use, and the guidelines provided by Oriental Medicine as well as by a long list of natural compounds that many authors identify as possible therapeutic or alternative agents to replace or to combine with the existing therapies will be included. Moreover, in the effort to provide the widest panel of remedies, the most antique techniques of acupuncture and electrostimulation will be considered as alternative, which are useful approaches to take into account in any non-pharmacological strategy for DPN management.
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Objective: To investigate the diagnostic significance of sensory nerve action protential (SNAP) on diabetic neuropathy (DN), through measuring amplitude and amplitude ratio. Methods: There were 91 patients with type 2 diabetes involing 51 cases without neurologic symptom/sign as subgroup I, 30 cases with mild neuropathy as subgroup II and 10 cases with severe neuropathy as subgroup III, according to Toronto clinical scoring system (TCSS). Thirty-nine healthy volunteers with age-and gender-matched were served as controls. SNAP were antidromically recorded using surface electrodes. The observed parameters were as follows: conduction velocity and amplitude of median, radial and sural nerve, shorten for Vme, Vra and Vsu and Ame, Ara and Asu, respectively; sural/radial nerve amplitude ratio (SRAR) and median/radial nerve amplitude ratio (MRAR). Results: (1) As compared with the controls (P < 0.05), conduction velocity (m/s, Vme: 46.2 ± 7.3, Vra: 45.8 ± 6.9, Vsu: 30.3 ± 9.5) and amplitude (μV, Am: 15.4 ± 10.5, Ar: 16.6 ± 9.8, As: 5.9 ± 6.3) decreased significantly in subgroup III; Vsu (46.2 ± 4.7) significantly slowed in subgroup II (P = 0.002); both Ame (34.5 ± 10.2, 33.0 ± 14.6) and Asu (13.8 ± 5.6, 10.7 ± 5.5) decreased significantly in both subgroup I and II respectively, with Asu decreasing more significantly in subgroup II (Z = -3.22, P = 0.001); SRAR (0.432 ± 0.112) was significantly smaller only in subgroup I, both SRAR (0.330 ± 0.102) and MRAR (1.008 ± 0.225) were significantly smaller in subgroup II. SRAR decreased more significantly in subgroup II (t = -3.86, P = 0.003). (2) The abnormal rate of Ame was the highest in subgroup I (26.0%), and Asu in subgroup II (41.4%); while that of combination of Asu and SRAR (68.9%) was significantly higher than that of Asu alone (X 2 = 9.212, P= 0.003). (3) TCSS scores were negatively related to Vsu (r = -0.583), Ame (r = -0.406), Asu (r = -0.620) and SRAR (r = -0.527, all P < 0.05), and there was no significant correlation of TCSS scores with MRAR in subgroup II; both SRAR (r = -0.435) and MRAR (r = -0.319) were negatively related to the diabetic duration (both P < 0.05). Conclusions: In mild or early DN, SNAP amplitude is more sensitive than conduction velocity, combination of SRAR and Vsu may be serve as a useful indication for early diagnosis. In the DN patient, diabetic duration has more influence on the measurement of sensory NCS, and SRAR is related to the severity of neuropathy.
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To assess the usefulness of the diagnostic and staging criteria for diabetic polyneuropathy (DP) by the Diabetic Neuropathy Study Group in Japan (DNSGJ) we examined clinical features, intraepidermal nerve fiber densities (IENFD) and nerve conduction studies (NCS) and coefficient of variation of the R-R intervals (CVR-R) in 44 patients with diabetes.ResultsThe patients were classified into stage I (n = 20), II (n = 6), III + IV (n = 12), and V (n = 6) according to the staging criteria by DNSGJ. IENFD decreased as stages progressed (13.8 ± 7.1 fiber/mm in stage I to 0.8 ± 1.3 fiber/mm in stage V). Compound motor and sensory action potential and motor and sensory nerve conduction velocity decreased with progressing stage. F-wave latency prolonged as stages progressed. CVR-R decreased with progressing stage (4.41% ± 2.65% in stage I to 1.33% ± 0.57% in stage V). IENFD correlated with the various parameters of NCS (r = 0.378–0.636, p < 0.05) and CVR-R (r = 0.399, p = 0.007).Conclusions Clinical staging for DP by DNSGJ reflects the results of small and large fiber neuropathy.
Article
Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes mellitus (DM). The aim of this study was to analyze DM duration in the prognosis of diabetic peripheral neuropathy of the lower extremity. A total of 1,526 DPN patients who were treated with DELLON surgical nerve decompression were divided into a short DM duration group and long DM duration group using a length of 5 years as the standard duration. Before and 1.5 years after surgery, high-resolution ultrasound, quantitative sensory testing (QST), and nerve conduction velocity (NCV) were performed and compared to the normal control. Postoperative NCV of all the patients in either treatment group significantly increased (p < 0.05) and postoperative CSA significantly decreased (p < 0.05) compared with that before surgery. The CPT significantly increased compared with the preoperative value (p < 0.05). The postoperative WPT was significantly lower than the preoperative value (p < 0.01), and the postoperative VPT was significantly lower than the preoperative value (p < 0.05). Overall, the postoperative NCV, CSA, CPT, WPT, and VPT values from the short DM duration group were significantly different from that of the long DM duration group (p < 0.05). The duration of DM is critical to the prognosis of DPN of the lower extremity, and the data from this study suggest that an early diagnosis and subsequent surgery for DPN have important clinical value.
Article
Aims Diagnosis of early distal symmetric polyneuropathy (DSP) is challenging. Nerve conduction studies (NCS) are often normal. Skin biopsy for intraepidermal nerve fiber density (IENFD) has better sensitivity, but is invasive. Sudoscan is a novel technology that measures electrochemical skin conductance (ESC, microSimens – uS), which is thought to be proportionate to the number of functional sweat glands. This study evaluated Sudoscan’s diagnostic utility for DSP Methods 55 patients with suspected DSP (22 with diabetes, 2 prediabetes, 31 idiopathic) and 42 controls underwent the Utah Early Neuropathy Scale (UENS) and Sudoscan. Each was offered skin biopsy. DSP participants underwent quantitative sudomotor axon reflex testing (QSART) and NCS. Results Feet and hands ESC were reduced among DSP participants compared to controls (64 +/- 22 vs. 76 +/- 14 uS p < 0.005, and 58 +/- 19 vs. 66 +/- 18 uS p < 0.04). There was no difference between diabetic and idiopathic DSP. Receiver operating characteristic curve analysis revealed feet ESC and IENFD had similar areas under the curve (0.761 and 0.752). ESC correlated with Sural amplitude (0.337, p < 0.02), UENS (-0.388, p < 0.004), and MNSI (-0.398, p < 0.005). Conclusions Sudoscan is a promising diagnostic test for diabetic and idiopathic DSP, with diagnostic performance similar to IENFD.
Article
To investigate the diagnostic significance of foot plantar pressure distribution abnormalities in patients with diabetic peripheral neuropathy (DPN). A total of 107 patients were divided into normal control (28 participants, 56 feet), non-DPN (56 patients, 112 feet), and DPN groups (23 patients, 46 feet). Foot plantar pressure was measured while patients walked at a constant speed over a flat floor using F-Scan pressure insoles. Recordings of six middle strides were averaged to evaluate the characteristics of foot plantar pressure distribution. Compared with the normal group, the time of contact (TOC) was longer in non-DPN (p < 0.05) and DPN groups (p < 0.01). The foot to floor force-time integral (FTI) was increased in DPN group (p < 0.01). The forefoot plantar force ratio increased in non-DPN and DPN patients (p < 0.05). Moreover, in DPN patients, the ratio of lateral foot plantar force increased (p < 0.05). The examination of the correlations between biomechanical parameters of the foot plantar and electrophysiological parameters of the lower limbs showed foot plantar biomechanical abnormalities correlated with abnormal sensory conduction of the sural nerve and motor conduction of the common peroneal nerve. Receiver operating characteristic (ROC) analysis showed the area under FTI curve was 0.714 (p < 0.001). The plantar pressure was shifted towards the side of the forefoot in DPN patients. The foot plantar biomechanical changes were closely correlated with lower limb paresthesia and contraction abnormalities of lower-limb extensor muscles. Foot plantar pressure measurement might be used as a screening tool for early diagnosis of DPN.