1. Electrophysiological Tests Used in the Evaluation of Peripheral Neuropathy and Neuropathic Pain David R. Cornblath, MD Johns Hopkins

2. Outline Electrophysiological Tests Natural History in Diabetes Correlation with Outcomes Use in Clinical Trials Practical Issues Summary

3. Neurophysiological Tests Nerve conductions: sensory and motor and F waves Electromyography Quantitative sensory testing Autonomic function testing QSART

4. Natural History of EDx Studies in Diabetes Most comprehensive data is the RDNS which shows a gradual worsening in neuropathy over time: -0.34 NIS(LL)+7 points/year in diabetes and -0.85 NIS(LL)+7 points/year in DPN. Depending on the treatment study examined, the data vary somewhat but all show worsening over time.

5. Correlation of Edx Tests with Outcomes The best data comes from Dr. Dyck and colleagues who suggest that a clinically detectable and meaningful change in neuropathy is a 2 point change in NIS which is equal to a 2.9 m/s or 1.2 mV change for avg. of median, ulnar and peroneal nerves or 2.2 m/s or 0.7 mV change for peroneal nerve alone.

6. EDx Tests in Clinical Trials Frequently used in neuropathy clinical trials as either primary or secondary endpoint. NCS show improvement when the change in diabetes is dramatic such as with transplantation, intensive control, or in children. NCS have not shown improvement in most clinical trials, but that may be a related to the lack of therapeutic successes or the parameter chosen.

7. Practical Issues What is the desired outcome? Which fiber population will be affected? What parameter of NCS will be affected? How fast will intervention work? Which test to use? What is hypothesized to occur from the intervention? Can this be done in multiple sites given the need for standardization, reproducibility, and reliability? Yes for NCS (see recent multi-center Japanese data)

8. Summary Peripheral Neuropathy Of the many tests, nerve conductions are the best studied and most accepted tests and correlate with clinical measures. A change over time is real. NCS can detect improvement or worsening. The other electrophysiological tests may be used in selected cases, but more data is needed on many of the practical issues. Nerve conductions are useful as part of composite measures of neuropathy such as NIS(LL)+7 and TNS.

9. Summary Neuropathic Pain Electrophysiological tests are valuable as a monitoring tool for toxicity. Nerve conductions should not be used as outcome criteria as they measure large fiber function, not small fiber function.