# Analysis of Factors Associated with Charcot Neuroarthropathy following Pancreatic Transplantation
## 4 Discussion  
This study examined the factors associated with CN development following pancreatic transplantation. Two important findings were identified in this study. First, while most patients who had undergone pancreatic transplantation had advanced neuropathy, those with CN had more severe neuropathy. [PERSON] et al. reported that >50% of patients with T1 DM in their study had DM-related peripheral neuropathy [16], suggesting that DM-related neuropathy develops early during DM onset. Multiple pathological conditions, such as ischemic stress, inflammation, oxidative stress, mitochondrial damage, and microangiopathy, have been found to be involved in the development of DM-related neuropathy [17]. Aggressive glycemic control is required to suppress the progression of neuropathy [18]. Most patients who undergo pancreatic transplantation in Japan face challenges in relation to glycemic control and have a long-term history of DM. The median duration of DM in this study was 28.5 years, which was a sufficient timeframe to develop severe neuropathy. Neurological examination results in relation to CN development show that all the patients who developed CN had no visualized waveforms of the sural nerve and a marked prolon  
Figure 3: **Comparison of incidence rates for CN based on severe peripheral neuropathy and a history of high-dose corticosteroids. ** No CN development was observed with or without high-dose corticosteroids in the presence of waveforms in the SCV test. In contrast, in the disappearance of the waveform in the SCV test, CN was observed in 2 of 11 patients (18%) without high-dose corticosteroids and in 4 of 5 patients (80.0%) with high-dose corticosteroids. In both instances, the frequency of onset was significantly higher in the group with visualized waveforms (with high-dose corticosteroids, \(p\) = 0.049; without high-dose corticosteroids, \(p\) < 0.01). Furthermore, the incidence rate was significantly higher when high-dose corticosteroids were used than when waveforms were not visualized in the SCV test (\(p\) = 0.036). CN, Charcot neuroarthropathy; SCV, sensory nerve conduction velocity. gation in the perception threshold test. When such test results are observed pre-operatively, a patient should be identified as being at an increased risk of developing CN. Perception threshold testing is recommended as a pre-operative test for patients undergoing pancreatic transplantation, as it is a simple test to perform compared with nerve conduction velocity tests. Second, the administration of high-dose corticosteroids was associated with the development of CN, but may not affect the incidence of CN when neuropathy is not severe. With corticosteroid administration as an immunosuppressant, bone mineral density decline progresses early after pancreas-kidney transplantation [19]. It has been suggested that immunosuppression protocols without steroid administration do not decrease bone density [20], but rather increase bone density due to the improved activities of daily living [21]. In addition to immunosuppressive protocols, high-dose corticosteroid administration increases the risk of further bone mineral density loss. Interestingly, four patients developed CN within 12 months of receiving high-dose corticosteroids. The remaining one patient developed CN within 12 months of transplantation. Five of the six patients developed CN within 12 months of high-dose corticosteroid administration (including the immunocompetent protocol); thus, it should be noted that a loss of bone mineral density soon after high-dose corticosteroid administration can increase CN development. In addition, in this study, most high-dose corticosteroid administration was intended for the treatment of rejection, but this treatment was also used for sudden deafness or cardiac arrest cases. High doses of corticosteroids may be required for unforeseen reasons. With severe neuropathy, meticulous bone density management is needed. In this study, there was no difference found in the T-scores between the CN and non-CN groups.