Establishment Of VX2 Hepatic Carcinoma Model And Study Of Electrophysiology In Paraneoplastic Peripheral Neuropathy

Paraneoplastic peripheral neuropathy is recognized as a remote effect caused by numerous malignancies or underlying tumors, which are generally concurrent with different types of peripheral nervous system disorders. Signs and symptoms seen in these patients are complex and diverse, resulting from cancer-associated lesions in any part of the peripheral nervous system and in a proportion of the PPN, an overlapping of central nervous system disorders or autonomic manifestations can be observed. Thus the diagnosis of paraneoplastic peripheral neuropathy is rather difficult, especially presenting with combination of clinical manifestations of the primary tumor. Currently the treatment response of PPN is poor owing to lack of specific treatment, severely affecting the patients’ quality of life and life expectancy. The only therapy that stabilizes this disease or gets improvement in prognosis is the tumor treatment itself. Therefore, enhancing recognition of paraneoplastic peripheral neuropathy is of great importance and it is crucial to diagnose and treat the primary tumor early. At present, diagnosis of paraneoplastic peripheral neuropathy depends mostly on the case history, clinical symptoms, electrophysiological examination and the detection of serum tumor markers or the associated paraneoplastic antibodies. In recent years, with our gradually increasing recognition of the electrophysiology, electrophysiological examination plays a prominent role in the diagnosis of paraneoplastic peripheral neuropathy. However, as regards electrophysiology, the current study mainly put emphasis on retrospective study of clinical cases, which makes it impossible to investigate the development of the whole course of the disease.Objective: The study was to analyze the characteristics of electroneurogram and F wave in rabbits with VX2 hepatic carcinoma, which is generally concurrent with paraneoplastic peripheral neuropathy, for the purpose of providing a more sensitive electrophysiological index for diagnosis of PPN.Methods: 22 healthy New Zealand white rabbits were randomly divided into experimental group(group A, n=12) and control group(group B, n=10). In group A, under conditions of a sterile sub-xyphoid laparotomy, several tumor fragments were inoculated into the liver parenchyma to establish VX2 hepatic carcinoma model. The control group received the same surgical treatment, but no tumor fragments were implanted into the wound in the liver. After the tumor transplantation, ultrasonography was applied to check the size and echo of tumors in group A and liver function was also detected to estimate the growth of tumors. After the rabbits died of natural causes, specimens were resected from both the liver and tumor aiming at pathological examination. Electroneurogram and F wave were detected regularly in the two groups with KEYPOINT myoelectric/evoked potential instrument. Statistical analyses were taken using data of the monitoring results of the rabbit VX2 carcinomas and electrophysiological examination.1.Detection of electroneurography : The recording electrode was pierced into the muscle belly of tibialis anterior and the reference electrode was pierced distally into the muscle tendon. Pierce the ground electrode between the stimulating and recording electrodes. The stimulating electrode was placed over the nerve with the cathode close to the recording electrode and the nerve was stimulated orthodromically. The current was gradually increased until the CMAP no longer enlarge and then increase the current by further 20 to 30 percent. CMAP was recorded with needle electrode and distal latency and amplitude were analyzed.2.Detection of F wave: The recording electrode was pierced into the muscle belly of tibialis anterior and the reference electrode was pierced distally into the muscle tendon. Pierce the ground electrode between the stimulating and recording electrodes. The stimulating electrode was placed over the nerve with the anode close to the recording electrode and the nerve was stimulated repeatedly 20 times. The current used was the same as mentioned above. The minimum F wave latency(Flmi), F-chronodispersion(Fchd), F-persistence(Fp) and F ratio(Fr) were analysed.Results: 1.The ultrasound images of different intervals after the inoculation, weight changes, autopsy and pathological findings all confirmed the presence of tumors in the experimental group. In two rabbits, the establishment of VX2 hepatic carcinoma model failed and three days after the implantation, one rabbit died. The success rate was 75%.2.Distal latency(DL) of peroneal nerve showed no difference between the two groups both before inoculation and 2 weeks after the surgery, the same as the amplitude of CMAP(P>0.05). 4 weeks and 6 weeks after the implantation, there were statistical differences in the amplitude between the two groups(P<0.01). There was no statistical difference in DL between the two groups 4 weeks after the surgery. But two weeks later, there was a significant difference in DL between the two groups(P <0.05).3.There was no statistical difference in all the indexes of F wave between the two groups both before inoculation and 2 weeks after the surgery(P>0.05). 4 weeks and 6 weeks after the implantation, there were statistical differences both in Fchd and Fp between the two groups(P<0.05). 4 weeks after inoculation, compared with the control group, Flmi and Fr in the experimental group did not change significantly(P> 0.05). But 2 more weeks later, the differences in the two indexes between the two groups were apparently(P<0.05).Conclusion: 1. Inoculation of tumor fragments under conditions of a sterile sub-xyphoid laparotomy is a stable method with high success rate and low dystopia implantation rate.2. Electrophysiological results suggest that the electrophysiological pattern of paraneoplastic peripheral neuropathy is mainly axonal degeneration, accompanied by demyelination.3.In screening for paraneoplastic peripheral neuropathy, emphasis should be put on the amplitude of CMAP,Fp and Fchd, especially Fchd. Along with aggravation of patient’s condition, DL and Flmi show abnormalities and Flmi is more likely to be abnormal.4.In the course of paraneoplastic peripheral neuropathy, pervasive demyelination can be seen and the lesion is more severe in proximal end.