Comparison of nerve conduction studies and f-waves in the diagnosis of diabetic peripheral neuropathy

Authors

Abstract

Aim
The aim of this study was to investigate whether there is a difference in sensitivity in the diagnosis of diabetic peripheral neuropathy and subclinical neuropathy between routine nerve conduction studies and F-waves examined with different numbers of stimuli in patients with diabetes mellitus.
Methods
In the study, eighty patients with diabetes mellitus (forty of them had symptoms of peripheral neuropathy) and forty healthy volunteers as control group were included. Those with peripheral neuropathy symptoms were included in the symptomatic group, and those without peripheral neuropathy symptoms were included in the asymptomatic group. All participants underwent routine nerve conduction study.
Results
According to the results of F minimum, F mean, and F maximum obtained with both 10 consecutive stimuli and 30 consecutive stimuli, there was a statistically significant difference between the symptomatic group and the control group as well as between the asymptomatic group and the control group (p<0.05). In F chronodispersion studies, there was no difference between groups at 10 consecutive stimuli and 30 consecutive stimuli (p>0.05).
Conclusion
F minimum, F mean, and F maximum tests were more sensitive than routine nerve conduction study in detecting asymptomatic diabetic peripheral neuropathies. The results of the tests with 10 and 30 stimuli were similar. F chronodispersion was found to be insensitive in the diagnosis of diabetic peripheral neuropathy and subclinical neuropathies.

Keywords

Introduction

Diabetes mellitus (DM) is one of the most important health problems recently.¹ It is a cause of mortality and morbidity due to complications in many organs and systems. Among the most important complications are neuropathy, nephropathy, and retinopathy. Diabetic Peripheral Neuropathy (DPN) is one of the most common complications.² DM affects nerves both acutely and chronically. Two theories have been proposed regarding the formation of neuropathy. Polyol pathway activation increases due to hyperglycemia and leads to neuropathy by causing sorbitol accumulation. Another hypothesis is endoneurial hypoxia due to vascular causes.¹ Both myelinated and unmyelinated nerves are affected. Affecting the myelinated fibers causes numbness in the distal extremities, unbalanced gait, muscle atrophy, and weakness. Painful neuropathy and autonomic symptoms occur when unmyelinated fibers are affected.² If DPN is not diagnosed and treated early, it causes foot ulceration and amputation, leading to disability.³ DPN is seen as symmetrical sensorimotor polyneuropathy.¹ It occurs as both axonal and demyelinating neuropathy.⁴ Sensory symptoms begin in the toes and affect the upper extremities over time. Motor symptoms appear later than sensory symptoms. After the sensory nerves are affected, patients experience a decrease in pain sensation, sensation of pins and needles, tingling, pain in situations where pain should not normally occur (allodynia), excessive pain (hyperalgesia), and hot-cold discrimination disorder.¹
In the presence of clinical findings, electrophysiological examinations and nerve conduction studies are performed to detect DPN.⁵ In DM patients, the presence of neuropathy can be revealed subclinically in nerve conduction studies without clinical findings.⁶ There is controversy regarding the fact that routine sensory and motor nerve conduction examinations are insufficient to detect DPN and subclinical neuropathies, and that F-wave examinations can reveal abnormalities before routine conduction examinations and are more sensitive.⁷
The F-wave is one of the most fundamental studies of clinical neurophysiology.⁸ It is called the F-wave because it was first shown on the lower extremities.⁶ It is produced by anterior horn cells and demonstrates excitability of spinal motor neurons. It is highly sensitive in detecting pathology of proximal segments.⁶
The amount of stimulus that should be administered supramaximally is controversial. In some studies, 10, 16, 20, or 32 stimuli were applied, and it was suggested that increasing the amount of stimulus gave more accurate results. However, some studies suggest that increasing the amount of stimulus is not an important factor.⁸
The aim of this study was to examine F-waves at different stimulus numbers (10, 30) between diabetic patients with and without DPN symptoms and control groups, and to compare whether there is a difference in sensitivity between routine nerve conduction examinations and F-wave examinations.

Materials and Methods

It was ensured that the skin temperature was 32–36 °C.⁹ The examination was performed by the same person who was blind to the clinical information of the patients. Informed consent prepared in accordance with the Declaration of Helsinki was obtained from all patient and control groups, and the approval of the local ethics committee was received (Date: 06.12.2021, Number: 13/06). Patients with renal failure, substance abuse, history of cerebrovascular or cardiovascular disease, cardiac pacemaker, neurotoxic drug use, drug use affecting the nervous system, malignancy, thyroid disease, cervical and lumbar trauma, and disc disease were excluded from the study.^5,10,11
Symptoms of peripheral neuropathy include unpleasant abnormal sensations in the distal extremities, touch, pain, decreased sensation of temperature, burning sensation in the feet, tingling, pins and needles, electrification, cramp-like sensation, decreased or absent ankle reflex, and muscle weakness. The Michigan Neuropathy Screening Instrument was used to differentiate between symptomatic and asymptomatic patients. According to the scale, those with a clinical examination score > 2 were considered symptomatic, and those ≤ 2 were considered asymptomatic.¹² A total of 120 people, including 40 DM patients with peripheral neuropathy symptoms, 40 DM patients without peripheral neuropathy symptoms, and 40 healthy controls, were included in the study. The examinations were performed in the lower extremities.
Nerve conduction study and F-wave examinations were performed with the Medelec Synergy model device. Sensory nerve conduction study was performed antidromically. Peak amplitude values and conduction velocities were measured in sensory nerve examinations and compared between the patients and control groups. Onset latency was defined as the time from the stimulus to the first negative deviation of the baseline for a biphasic sensory nerve action potential (SNAP) or the first positive peak for a triphasic SNAP. The amplitude was evaluated as the amplitude measured between the first electronegative peak and the second electropositive peak. In motor nerve examinations, compound muscle action potentials (CMAP) recorded with distal and proximal stimulation, motor distal latency, peak amplitude values, and conduction velocities were measured and compared between groups. Latency was defined as the time elapsed between the stimulus and the point where the potential left the baseline in the electronegative direction. The amplitude was evaluated as the oscillation between the baseline and the electronegative peak. Motor nerve conduction velocity was calculated by subtracting the distal latency of the CMAP obtained with distal stimulation from the proximal latency of the CMAP obtained with proximal stimulation, and dividing the distance between the two stimulation points by this differential latency.¹³
For sural nerve conduction examination, the recording electrode was placed behind the lateral malleolus. Stimulation was performed 12 cm proximal to the recording electrode, from the middle posterior part of the leg.¹⁰ The recording electrode was placed on the extensor digitorum brevis muscle for peroneal motor nerve conduction examination. The peroneal nerve was stimulated distally at the ankle level, laterally from the tibialis anterior muscle tendon, and proximally from the distal fibula head. For tibial nerve motor conduction examination, the recording electrode was placed on the abductor hallucis muscle. The tibial nerve was stimulated from behind the medial malleolus and from the popliteal fossa.¹⁴
For the F-wave study, electrodes were placed as for the motor nerve conduction study. For tibial and peroneal F-wave examination, supramaximal stimulus was applied from the retro-malleolar region and lateral to the tibialis anterior tendon at the ankle, respectively.¹⁰ For F-wave recording, 10 (F-10) and 30 (F-30) supramaximal stimuli were obtained separately by antidromic application. F-waves were recorded while the patients were at rest. As a result of supramaximal stimulation, they were distinguished by longer, variable latency, low shape, and amplitude after the M wave. Regardless of whether the initial deflection was positive or negative, the initial latency was accepted as the starting point of the response. Minimum latency (F min), maximum latency (F max), mean latency (F mean), and chronodispersion (F cd) measurements of the F-wave were made. Waves greater than 20 µV were considered F-waves. F-wave was measured peak-to-peak. The F-wave with the shortest latency was accepted as F min. F mean was obtained by dividing the sum of the initial latencies by the number of F-waves.^10,11 F max was accepted as the longest duration F-wave. F cd was accepted as the difference between the maximum and minimum F-wave. The latency of the F-wave is directly proportional to limb length; height can also be used instead of limb length.¹⁵ In this study, height was used in the evaluation between groups. F-wave was obtained with distal stimulus from the ankle. Signals were recorded at an amplification of 500 µV/div during a 100-ms period following the stimulus.¹⁶
Weight and height were measured in the lightest clothing possible and without shoes. The study was carried out in Type-2 DM patients.
Biochemical Analysis
Venous blood samples for biochemical analysis were obtained after at least 10 hours of fasting and before any drug administration. All biochemical analyses were performed in the Local Central Biochemistry Laboratory.
Statistical Analysis
Statistical analysis was performed using the IBM SPSS v.19 package program (IBM Corp., Armonk, USA). The statistical level of significance for all tests was considered to be 0.05. The results were presented for continuous variables as mean ± standard deviation (SD), median, and minimum–maximum. The normality of distribution for continuous variables was confirmed with the Shapiro-Wilk test. For comparison of independent continuous variables between 3 groups, analysis of variance (ANOVA) or Kruskal-Wallis test was used. Homogeneity of variances was confirmed with Levene’s test. While comparing 2 groups, Tukey HSD, Games-Howell, or Mann-Whitney U test was used as post-hoc test. Pearson’s chi-square test was used for the analysis of qualitative groups. Bonferroni adjustment was made for nonparametric pairwise multiple comparison tests in independent groups.
Ethical ApprovalEthics Committee approval for the study was obtained.

Results

Descriptive statistics values between symptomatic, asymptomatic and control groups are shown in Table 1. No significant difference was observed between the groups in terms of gender, age, weight, height, body mass index (BMI), duration of diabetes and HbA1c levels (p>0.05).
In the examination of the sural sensory, the common peroneal motor and the tibial motor nerves, there was a significant difference between symptomatic DM patients and the control group in terms of amplitude, conduction velocity and latency values (p<0.05); however, there was no significant difference between asymptomatic patients and control group (p>0.05), (Table 2).
As shown in Table 3, groups were examined separately with 10 and 30 stimulus numbers. When the common peroneal motor nerve and the tibial motor nerve were examined in terms of F min, F max, and F mean in both 10 and 30 stimulus numbers, it was found that there was a significant difference between the symptomatic group and the control group, and between the asymptomatic group and the control group (p<0.05). There was no significant difference between the groups in the examination of F cd values (p>0.05).

Discussion

DPN occurs due to metabolic and microvascular causes such as hyperglycemia, decreased Na/K ATPase enzyme activity, increased anaerobic glycolysis, oxidative stress, mitochondrial dysfunction, polyol pathway activation, and microangiopathy.⁷ The majority of patients develop DPN despite good glucose control. However, the first choice in the treatment of DPN is glycemic control.^1,17
Motor and sensory nerve conduction examinations are performed for the diagnosis of DPN.¹ Studies have shown that there is increased sensitivity in the proximal segments of the nerves in the early stages of diabetes, and it is necessary to examine the proximal segments for the diagnosis of subclinical diabetic neuropathy.¹¹ It has been suggested that sensory and motor examinations are insufficient to examine the long proximal segment of the nerve; therefore, routine nerve conduction studies are insufficient for the early diagnosis of diabetic subclinical neuropathy.¹⁸
When the motor nerve is stimulated from any point, it creates a compound muscle action potential in the muscle tissue with orthodromic conduction. The antidromic conduction stimulates some cells of the anterior horn. The impulses from the anterior horn cells cause an additional small depolarization of the muscle. This depolarization is called F-waves.⁶ The F-wave is the late wave that occurs after supramaximal stimulation of the motor nerve. It also gives information about the state of motor neurons in the cervical and lumbosacral cords. The afferent and efferent pathway of the F-wave is the alpha motor neuron.³ Ensuring glycemic control has the fastest effect on F-waves and is the most important follow-up investigation that gives the fastest response to glycemic changes.⁷
DPN begins earlier in the lower extremities than in the upper extremities. It has been suggested that sural sensory potential is the earliest examination to show abnormality in diabetes. It shows abnormality before the peroneal and tibial motor nerves. However, it has been suggested that the F-wave is affected before the sural nerve.¹⁹ F min reflects the fastest motor neurons.²⁰ F min elongation is explained by loss of the most rapid axons or decreased excitability of anterior horn cells.⁴ F mean is an average measure of all axons.¹⁵ F max reflects slow conducting motor neurons.²¹ A few of the anterior horn cells are stimulated with each stimulation. For this reason, there are debates about whether at least 10 or 20 stimulations will give accurate results. In many studies, it was seen that between 10 and 32 stimuli were used, and in a few studies, stimuli were given below or above this number.^4,6 While 5 or 10 measurements are sufficient for the objective criterion for F mean, it has been reported that more stimuli should be applied for F min, F max, and F cd. It is recommended that the number of stimuli applied should be at least 30 in order to evaluate F cd correctly.⁶
There are studies reporting that the most sensitive test for the early diagnosis of diabetic subclinical neuropathy is the F min examination, and the lower extremity tibial and peroneal F min examination is the most sensitive test.¹ In some studies, F min and F mean examinations in the lower extremities were shown to be the most sensitive findings.¹¹ In one study, F max and F mean values were found to be more sensitive than F min values when the healthy group and diabetic patients were compared, but this study was reported as a small study.²²
It has been shown that F-waves are associated with the duration of diabetes and HbA1c levels and are affected by these parameters. F-waves are significantly prolonged in patients with neurological examination findings and sensory symptoms.⁶
In the present study, 10 and 30 stimuli were applied separately to the patient and control groups. The patient and control groups were compared with different numbers of stimuli. There was no significant difference in terms of F cd values in 10 and 30 stimuli. Thus, F cd was not sensitive to detect symptomatic or non-symptomatic patients with diabetes and does not support studies suggesting that F cd is sensitive. In routine nerve conduction examination, symptomatic patients were significantly different from the control group, but asymptomatic patients and control group were similar. Therefore, routine nerve conduction examinations were insufficient for the early detection of asymptomatic patients.
There were significant differences between symptomatic patients and control groups and between asymptomatic patients and control groups in both 10 and 30 stimuli; F-wave examinations were more sensitive than routine examination in early detection of asymptomatic patients and subclinical neuropathies. Examinations at different stimulus numbers did not make any difference in sensitivity. Sensitivity did not change in F min, F max, and F mean examinations at 10 and 30 stimuli.

Conclusion

Routine nerve conduction examination detected symptomatic patients, but it was insufficient to detect asymptomatic patients. F-wave examination was more sensitive than routine examination in detecting subclinical neuropathy in asymptomatic patients. F min, F max, F mean did not show any difference in sensitivity at different number of stimuli. F cd examination was similar in diabetes and control groups and its use in detection of peripheral neuropathies was not sensitive.

Declarations

References

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About This Article

Received:

November 13, 2022

Accepted:

December 24, 2022

Published Online:

January 5, 2023

Printed:

February 1, 2023