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Abstract
Objective: The purpose of this study was to determine the changes in the amplitudes of a sensory nerve action potential (NAP) to a
conditioning stimulus given prior to a test stimulus at 2 – 8 ms intervals in healthy subjects and patients with diabetes mellitus with no clinical
signs of neuropathy and normal nerve conduction velocities (NCVs), to be able to diagnose peripheral neuropathy at its very early stages.
Methods: NAPs in the superficial branch of the radial nerve were recorded in healthy subjects (28 women and 7 men) and type II diabetes
patients without neuropathy (22 women and 12 men). Radial nerve was first stimulated with a single shock and then with double shocks at
intervals of 2, 3, 4, 5, 6, 7, and 8 ms; NAP amplitudes and NAP1/NAP2 ratios were calculated in normals and diabetics. NCVs were within
the normal ranges (.50 m/s) in all subjects.
Results: Of the independent variables—group (control, patient), sex (male, female), and hand (right, left)—only group significantly
influenced NAP amplitude; mean NAP amplitude (single shock) was significantly lower in patients than controls. NAP1/NAP2 ratios were
slightly below one (facilitation) in controls; it was above one at 1 – 8 ms stimulus intervals (inhibition) in diabetics, which was strongest at
smallest intervals, gradually decreasing, and almost disappearing as the stimulus interval approached 8 ms.
Conclusions: Using double-shock stimuli, an early diagnosis of peripheral neuropathy would be possible in diabetics without clinical signs
of peripheral neuropathy and exhibiting no slowing in NCV.
q 2003 International Federation of Clinical Neurophysiology. Published by Elsevier Science Ireland Ltd. All rights reserved.
Keywords: Diabetic neuropathy; Nerve action potential; Refractory period; Peripheral nerve; Excitation; Inhibition
to 73% with refractory period measurements. Braune (1999) consequent trials. In this study, we chose the superficial
measured the sural and radial nerve’s relative refractory radial nerve, since it is a pure sensory nerve and easy to
periods with double shocks and found pathological access. The amplitudes of the NAPs were measured from
reduction of sural NCV in 4 of 30 patients, two of them baseline to peak; the ratio of the amplitudes for the first and
with additional reduction of radial NCV. The NCVs were second NAPs (NAP1/NAP2) was calculated. We have taken
below normal in these patients. Therefore, the author has subjects only with normal NCVs (. 50 m/s).
suggested that “the measurements should be performed if n. The statistical package SPSS for Windows (Version
suralis NCV is normal”. 10.0) was used for statistical analysis. ANOVA was used to
The above studies indicated that measurements of the determine whether there were any significant differences
relative refractory period are more sensitive in detection of between the NAP1/NAP2 ratios for the right and left hands
neuropathy than NCV alone. In light of the above- in healthy subjects and diabetic patients in men and women.
mentioned studies, the response characteristics of a sensory So, the following factors were considered: sex, hand, and
nerve to double-shock stimulations seem to be very groups (normal and diabetic); the dependent variable was
important in diagnosis of peripheral neuropathy at its very NAP1/NAP2. The traditional level of significance ðp ¼
early stages. In doing so, the therapeutic interventions 0:05Þ was also accepted for the present study.
would be more successful than those at the irreversible
stages of neuropathy. Therefore, we have studied the
response characteristics of a sensory nerve to a conditioning 3. Results
stimulus applied at relatively short intervals, to be able to
diagnose neurodegenerative changes in diabetic patients In single-shock stimulations, sex was not a significant
exhibiting no clinical signs of neuropathy and having factor influencing the amplitudes of the NAPs from the right
normal NCVs. Sex and hand preference of the subjects were and left hands (F ¼ 0:06, p . 0:05). There was also no
also considered, since these factors have been reported to significant difference between NAPs from the right and left
influence the peripheral NCVs (see for instance, Tan and radial nerves, that is, the difference between sides was also
Tan, 1995, 1998a,b). insignificant (F ¼ 0:03, p . 0:05). Therefore, the data
obtained from the right and left sides were combined.
At single-shock stimulations, there was a significant
2. Methods difference between the mean amplitudes of the NAPs in the
control and diabetic groups (independent variables): the
Thirty-four type II diabetes mellitus patients (22 women mean amplitude of the NAPs was significantly smaller in
and 12 men, average age: 55 ^ 4.8) were included in the diabetics than controls (F ¼ 11:5, p , 0:001) and the mean
study. The average duration of diabetes was 2 years. amplitudes of the radial NAPs were 9.4 ^ 2.5 and 7.4 ^ 2.5
Subjects with histories of trauma and cervical disk mV for the healthy and diabetic groups, respectively. The
herniation were excluded. Patients had no clinical findings box-and-whisker plots in Fig. 1 illustrates the median values
for diabetic neuropathy with respect to neurological and (line across the boxes), interquartile range (50% of values),
electrophysiological examinations. The control group minimum, and maximum values of the NAPs (caps) for the
comprised of 35 healthy subjects (28 women and 7 men, control and diabetic groups.
average age: 52 ^ 6.2) with no history of neurological There was a significant difference between the diabetic
disease. On the morning of electrophysiological examin- and control groups in terms of NAP1/NAP2 ratios for 2 ms
ation, the subjects had breakfast and, if required, took their stimulus intervals (F ¼ 30:6, p , 0:001): the average ratios
antidiabetic medication. In addition to general physical were found to be 1.36 ^ 0.35 mV for the diabetic group and
examination, a detailed neurological examination was 0.99 ^ 0.26 mV for the control group. The significant
carried out. Standard electrophysiological tests were difference between the healthy and diabetic groups
performed on all patients, and patients with polyneuropathy continued at 3 and 4 ms intervals ðp , 0:000Þ, but at 5
were excluded from the study. Care was taken to maintain and 6 ms intervals, the significance began to decrease
extremity temperature above 33 8C, with heating as (p , 0:001 and p , 0:004 for 5 and 6 ms, respectively).
necessary. In order to record sensory nerve action potentials There was no significant difference between the control and
(NAP), the recording electrodes were attached to the thumb patient groups at 7 ms stimulus interval (F ¼ 3:5,
and stimulus electrodes were placed over the radial nerve on p . 0:05).
the radius. The distance between the recording and stimulus Fig. 2 illustrates the relationships between stimulus
electrodes was 100 mm. The stimulus intensity just for the intervals and NAP1/NAP2 ratios in controls (closed circles,
maximal NAP was determined. Then, at the same stimulus straight line) and diabetics (open circles, dashed line). As
intensity, the sensory radial nerve (ramus superficialis) was seen in Fig. 2, the mean ratios in the control group were
stimulated first with a single shock followed by double consistently below one, while those for the diabetic group
shocks at intervals of 2, 3, 4, 5, 6, 7, and 8 ms, during which were above one. Interestingly, although there are no striking
the NAPs were recorded. There were 2 s intervals between differences between the ratios in the control group, the ratios
M. Tan, U. Tan / Clinical Neurophysiology 114 (2003) 1419–1422 1421
4. Discussion
Fig. 2. The relationships between double-shock intervals (abscissa) and NAP1/NAP2 ratios (ordinate) for controls (closed circles, straight line) and diabetics
(open circles, dashed line).
1422 M. Tan, U. Tan / Clinical Neurophysiology 114 (2003) 1419–1422
Acknowledgements
References
Braune HJ. Testing of refractory period in sensory nerve fibres is the most
sensitive method to assess beginning polyneuropathy in diabetics.
Electroenceph clin Neurophysiol 1999;39:355–9.
Brismar T, Sima AA, Greene DA. Reversible and irreversible nodal
dysfunction in diabetic neuropathy. Ann Neurol 1987;21:504 –7.
Burke D, Kiernan MC, Bostock H. Excitability of human axons. Clin
Neurophysiol 2001;112:1575–85.
Horn S, Quasthoff S, Grafe P, Bostock H, Renner R, Schrank B. Abnormal
axonal inward rectification in diabetic neuropathy. Muscle Nerve 1996;
19:1268– 75.
Lowitzsch K, Hoff HC, Schlegel HJ. Conduction of two or more impulses in
relation to the fibre spectrum in the mixed human peripheral nerve. In:
Fig. 3. Box-and-whiskers plots for NAP1/NAP2 ratios in control (A) and Desmedt JE, editor. New developments in electromyography and
diabetic groups (B) for various interstimulus intervals. Boxes, interquartile clinical neurophysiology, vol. 3. Basel: Karger; 1973. p. 272–8.
range which contains 50% of values; whiskers, largest and smallest values Mogyoros I, Lin C, Dowla S, Grosskreutz J, Burke D. Reproducibility of
observed. indices of axonal excitability in human subjects. Clin Neurophysiol
2000;111:23–8.
to 8 ms. Additionally, we performed our study in patients Quasthoff S. The role of axonal ion conductances in diabetic neuropathy: a
with normal NCVs. We have usually observed facilitatory review. Muscle Nerve 1998;21:1246 –55.
Ruijten MW, De Haan GJ, Michels RP, Pruijs-Brands A, Ongerboer de
influences in double-shock experiments in healthy subjects
Visser BW, Verberk MM. Motor nerve refractory period distribution
and inhibitory influences in diabetic subjects. These original assessed by two techniques in diabetic polyneuropathy. Electroenceph
results suggest that the double-stimulus technique may be of clin Neurophysiol 1994;93:306–11.
utmost importance in detecting the very early changes in Schutt P, Muche H, Lehmann HJ. Refractory period impairment in sural
diabetic nerves before the appearance of any clinical signs nerves of diabetics. J Neurol 1983;229:113–9.
Tackmann W, Lehmann HJ, Ullerich D. Refractory period in human
of neuropathy in patients even with normal NCVs. This
sensory nerve fibres—transmission of frequent impulse series in human
conclusion cannot, however, be applied to all individual sensory nerve fibres. Eur Neurol 1974;12:277–92.
cases, since there were overlappings between both groups as Tan M, Tan U. The motor conduction velocities of the median and ulnar
Fig. 3 clearly shows. nerves in relation to the carpal tunnel diameters in the male and female
In conclusion, we have studied the effects of conditioning controls and carpet weavers. Int J Neurosci 1998a;94:223–32.
Tan M, Tan U. Correlation of carpal tunnel size and conduction velocity of
stimulus (NAP1) on the test stimulus (NAP2) with stimulus
the sensory median and ulnar nerves of male and female controls and
intervals of 2– 8 ms in healthy subjects and diabetic patients carpet weavers. Percept Mot Skills 1998b;87:1195–201.
exhibiting normal NCVs and no clinical signs of neuro- Tan M, Tan U. Possible lateralization of peripheral nerve conduction
pathy. In normal subjects, the NAP1 usually evoked associated with gender. Percept Mot Skills 1995;81:939–43.