|Year : 2007 | Volume
| Issue : 4 | Page : 252-254
Serial nerve conduction studies of the tail of rhesus monkey ( Macaca mulatta ) and potential implications for interpretation of human neurophysiological studies
William A Graham1, Richard Goldstein1, Mansfield Keith2, Shanker Nesathurai1
1 Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA, USA
2 New England Primate Research Center, Harvard Medical School, Southborough, MA, USA
Physical Medicine and Rehabilitation Hospital, Harvard Medical School, 125, Nashua Street, Boston, MA - 02114
Source of Support: None, Conflict of Interest: None
| Abstract|| |
It is well accepted in clinical medicine that nerve conduction studies are helpful in the diagnosis of diabetic peripheral neuropathy. However, some clinicians utilize serial nerve conduction studies to make inferences regarding the progression of peripheral neuropathy. The validity of this clinical construct has not been established. In order to determine the variability in serial nerve conduction studies, sensory and motor responses were obtained from the caudal nerve of the tail of a diabetic monkey. In particular, the sensory and motor nerve conduction studies were obtained on seven separate occasions over a period of 4.5 months in a diabetic Macaca mulatta monkey. The coefficient of variation in the motor onset latency, motor amplitude, sensory onset latency and sensory amplitude was 10.7%, 56.4%, 4.2% and 23.4%, respectively. These results suggest that physicians should be cautious in making clinical inferences based on the changes in serial nerve conduction studies.
Keywords: Neuropathy, nerve conduction studies, diabetes
|How to cite this article:|
Graham WA, Goldstein R, Keith M, Nesathurai S. Serial nerve conduction studies of the tail of rhesus monkey ( Macaca mulatta ) and potential implications for interpretation of human neurophysiological studies. Ann Indian Acad Neurol 2007;10:252-4
|How to cite this URL:|
Graham WA, Goldstein R, Keith M, Nesathurai S. Serial nerve conduction studies of the tail of rhesus monkey ( Macaca mulatta ) and potential implications for interpretation of human neurophysiological studies. Ann Indian Acad Neurol [serial online] 2007 [cited 2019 Jul 17];10:252-4. Available from: http://www.annalsofian.org/text.asp?2007/10/4/252/37818
Diabetic peripheral neuropathy is a significant clinical and public health challenge. Population studies indicate that 6.5% of Americans have diabetes mellitus  and 50-60% of these individuals suffer from peripheral neuropathy.  This condition affects the motor, sensory and autonomic nerve fibers. Numbness, tingling, burning and shooting pain are attributed to the impairment of the sensory nerve fibers. Muscle wasting and weakness are related to dysfunction of the motor nerves. Orthostatic hypotension as well as urinary and sexual dysfunctions are some of the abnormalities in the autonomic nervous system. Limbs that have impaired sensation may be more predisposed to the development of skin ulcers, which are antecedent to limb amputations many times.
It is accepted in clinical medicine that abnormal nerve conduction studies are helpful in the initial diagnosis of diabetic peripheral neuropathy. However, some clinicians utilize the serial worsening of nerve conduction parameters to infer that the peripheral neuropathy of the patient is progressing. Some experts have argued that serial studies on individual subjects provide "objective methods" for determining the progression of neuropathy.  However, the validity of this clinical construct has not been established.
To further evaluate if serial nerve conduction studies are helpful in assessing the progression of diabetic peripheral neuropathy, sensory motor and nerve conduction studies were obtained from a Macaca mulatta with spontaneous diabetes. The nerve conduction studies were obtained from the tail on seven separate occasions over a time frame of 4.5 months. Nerve conduction studies of the tail can be easily performed and have many technical advantages.  This report is unique. To the best of our knowledge, this is the only study of serial nerve conduction studies in the same nonhuman primate subject. Furthermore, there are very few reports of serial nerve conduction studies on the same subject in human beings.
In order to gather preliminary data for a larger study on diabetic peripheral neuropathy, the sensory and motor responses from the caudal nerves of the Macaca mulatta in one subject were obtained on a serial basis. The Harvard Medical Area Standing Committee on Animals approved all the procedures used for this study. This study was performed using a 15-year-old female rhesus macaque ( Macaca mulatta ) with spontaneous diabetes. The subject was diagnosed with diabetes mellitus approximately 1 month prior to initiation of this research project. The animal weighed 8.1 kg at the time of diagnosis and had a random blood sugar of 186 mg/dl. The diagnosis of diabetes was subsequently confirmed with fasting serum glucose levels. This study was performed over a period of 4.5 months on seven separate occasions. The fasting serum blood sugar ranged from 165 to 236 mg/dl and the bodyweight of the animal ranged from 8.2 to 8.7 kg throughout the study period.
The nerve conduction testing method has been described previously.  Briefly, the animal was sedated with 4-5 mg/kg of Telazol intramuscularly and was then administered with 2-3 mg/kg bolus of Propofol intravenously. Skin temperature was at least 32°C and remained constant ± 0.5°C during the testing period. The entire tail was shaved with a razor and cleansed with alcohol wipes. Reference marks for electrode placement were made using an indelible marker at 4, 7, 12, 17 and 20 cm from the distal tail. Circumferential disposable surface self-adhesive electrodes were used in this study.
Nerve conductions were performed using a Sierra II EMG/NCS apparatus (Cadwell, Kennewick, WA) that was interfaced with a constant current stimulator (Digitimer, UK). Technical measures were undertaken to reduce the stimulus artifact such as cleaning the skin, use of disposable electrodes and electrically isolating the stimulator form the rest of the neurophysiological equipment.
To obtain motor nerve conduction responses, the electrical stimuli were delivered to the base of the tail (i.e., reference points 17 and 20). The evoked response was recorded at 4 cm (reference) and 7 cm (active) points. The ground cable was the 12 cm electrode. The stimulus intensity was increased until a supramaximal response was obtained. To obtain maximal motor responses, 20-40% of the maximal stimulator output was necessary. The motor nerve conduction responses were collected first, and then 4-5 min later, the sensory nerve conduction responses were collected.
To obtain the sensory nerve response (mixed nerve response), the electrical stimulus was delivered at the end of the tail (i.e., reference points 4 and 7). The evoked response was recorded at the 17 cm (reference) and 20 cm (active) points. The ground cable was the 12 cm electrode. To obtain supramaximal sensory responses, 30-80% of the maximal stimulator output was required. The responses were averaged 10 times.
The "normal values" for the sensory and motor responses from the caudal nerve of the tail was previously reported on ten apparently healthy monkeys ( Macaca mulatta ).  Based on this previous study, in this subject, the sensory latencies were below the 10 th percentile and the motor latencies were between the 10 th and 20 th percentile. The sensory and motor amplitudes were between the 30 th and 40 th percentile. There was no neurophysiological evidence of the progression of the peripheral neuropathy over the course of the study period of 4.5 months [Table - 1].
The data indicates that the random error with serial nerve conduction studies is substantial. The random error is twice the coefficient of variance. If one were to extrapolate the nonhuman primate data to humans with diabetes mellitus, a change in the sensory and motor nerve conduction amplitudes, from one day to another, of 46 and 112% would still be considered as "acceptable". Similarly, a change in sensory and motor latencies of 8 and 22% would also be considered as "acceptable". These stated measures of variability assume 100% reliability - i.e., each test is performed in exactly the same manner. However, it is unlikely that the reliability, even with the most expert of clinicians, is 100%. As such, the previously mentioned random errors understate the true random errors in the serial nerve conduction studies.
It is clear that human beings and nonhuman primates differ in many ways. Nevertheless, the precision in measuring nerve conductions in the tail of the monkey is probably greater than the studies on human beings. For example, unlike in the studies on humans, the subjects are sedated. The nerves of the tail are straight and surface recording of length probably corresponds to the actual length of the nerve.  In contrast, in nerve conduction studies on human beings, the course of the nerve does not clearly correspond with surface measurement (i.e., peroneal nerve at fibular head). For all the foregoing reasons, the variance in nerve conduction measurements in monkeys should be less than the variance in human beings.
As stated previously, there is paucity of studies evaluating the normal variance with serial nerve conduction studies. , Bleasel obtained serial measurements on one apparently healthy normal human subject over a period of 3 months. A number of sensory and motor nerves were studied. The CoV for the sensory and motor velocities ranged from 3.8-6.7 and 2.2-5.6%, respectively. The CoV for sensory amplitudes ranged from 26-32% and the motor amplitudes had a CoV that ranged from 8.5-15.7%. Bergman also obtained nerve conduction studies in a single normal subject; he studied the median and ulnar nerves in a serial manner. The CoV for the sensory and motor conduction velocities varied from 4.2 to 4.7% and 4.4 to 5.6%, respectively.
It should be noted that this study involved only one subject. In this context, inferences based on this data should be considered preliminary. Nevertheless, in the nonhuman primate subject studied, the coefficient of variance in the motor amplitudes was substantially greater than in the normal healthy human subjects studied by Bleasel and Bergman. This observation is not necessarily discordant. It is important to recognize that the standard deviation and CoV in a healthy population may not necessarily be similar in a diseased population. Cross-sectional studies comparing nerve conduction responses in normal control subjects vs diabetic neuropathy patients have reported an increased CoV in the patients with diabetic neuropathy. , However, these studies did not evaluate the variance in the measured parameters on repeated tests on the same subject.
In conclusion, we caution our colleagues on making clinical inferences regarding the progression of peripheral neuropathy on the basis of serial abnormalities in nerve conduction studies.
| Acknowledgments|| |
We would like to thank Dr. Ludlage and other staff at the New England Primate Research Center for providing us with invaluable help and advice with the experimentation involved in these studies. We would also like to thank Mr. Luke Richards for excellent technical support. These studies were completed in accordance with the Harvard Medical Area Standing Committee on the ethical treatment of Animals, Harvard University.
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[Table - 1]
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