交感皮肤反应在糖尿病周围神经病变诊断中的应用

糖尿病周围神经病变（Diabetic Peripheral Neuropathy,DPN）是糖尿病最常见的并发症之一。由于目前DPN发病机制不清楚、治疗效果不理想,故早诊断、早治疗显得至关重要。有研究指出交感神经皮肤反应（Sympathetic Skin Response,SSR）可作为评价2型糖尿病患者早期周围植物神经功能状态的指标。本文对SSR应用于DPN临床诊断中的检测技术、观测参数进行综述,发现多数研究中指出,在临床应用中SSR波形、波幅以及潜伏期指标的异常率常受到多种因素的影响、会发生很大波动,而电位曲线下面积减少值相对稳定。据此笔者建议在DPN早期临床诊断中以SSR电位曲线下面积减少作为关键参数,辅助参考SSR波形、波幅以及潜伏期指标进行诊断。     

Exenatide Facilitates Recovery from Oxaliplatin-Induced Peripheral Neuropathy in Rats

Background

Oxaliplatin has widely been used as a key drug in the treatment of colorectal cancer; however, it causes peripheral neuropathy. Exenatide, a glucagon-like peptide-1 (GLP-1) agonist, is an incretin mimetic secreted from ileal L cells, which is clinically used to treat type 2 diabetes mellitus. GLP-1 receptor agonists have been reported to exhibit neuroprotective effects on the central and peripheral nervous systems. In this study, we investigated the effects of exenatide on oxaliplatin-induced neuropathy in rats and cultured cells.

Methods

Oxaliplatin (4 mg/kg) was administered intravenously twice per week for 4 weeks, and mechanical allodynia was evaluated using the von Frey test in rats. Axonal degeneration was assessed by toluidine blue staining of sciatic nerves.

Results

Repeated administration of oxaliplatin caused mechanical allodynia from day 14 to 49. Although the co-administration of extended-release exenatide (100 μg/kg) could not inhibit the incidence of oxaliplatin-induced mechanical allodynia, it facilitated recovery from the oxaliplatin-induced neuropathy with reparation of axonal degeneration. Inhibition of neurite outgrowth was evaluated in cultured pheochromocytoma 12 (PC12) cells. Exenatide inhibited oxaliplatin-induced neurite degeneration, but did not affect oxaliplatin-induced cell injury in cultured PC12 cells. Additionally, extended-release exenatide had no effect on the anti-tumor activity of oxaliplatin in cultured murine colon adenocarcinoma 26 (C-26) cells or C-26 cell-implanted mice.

Conclusion

These results suggest that exenatide may be useful for treating peripheral neuropathy induced by oxaliplatin in colorectal cancer patients with type 2 diabetes.     

Peripheral Neuropathy Following Chloroquine Therapy

Four patients were observed who developed similar episodes of peripheral neuropathy following prolonged treatment with chloroquine phosphate. This previously unreported toxic reaction consisted of bilateral loss of knee and ankle reflexes and weakness of the quadriceps muscles. Gradual return to normal followed withdrawal of the chloroquine. Other toxic reactions to the drug are reviewed.     

Peripheral Neuropathy and Experimental Myeloma in the Mouse

SEVERAL forms of generalized and localized peripheral neuropathy have been associated in man with solitary or multiple myeloma^1–3. The cause of the nerve damage, which usually involves segmental demyelination^{4, 5} (that is, a specific lesion of the Schwann cell-myelin sheath) as well as some total nerve fibre degeneration, is unknown and so is its relationship to the protein produced by the abnormal plasma cells. The disorder has been classed as one of the “non-metastatic neurological complications of neoplasms”⁶, a group of mysterious disorders, almost all of unknown cause, which have not so far been reproduced in experimental animals. Recently, histological studies on the peripheral nerves of mice bearing transplanted plasma cell myelomas have shown that tumours secreting a particular type of protein are associated with a similar mixed peripheral neuropathy.     

紫杉醇所致SD大鼠外周神经病变模型的建立

目的 化疗药物所致的外周神经病变（chemotherapy-induced peripheral neuropathy,CIPN）是多种化疗药物的共同而严重的不良反应.目前,国内外最常用的CIPN模型是紫杉醇（PTX）腹腔注射建立的SD大鼠模型,但关于影响CIPN模型建立的相关因素却少有涉及.本实验拟考察影响PTX所致SD大鼠CIPN模型的影响因素,为筛选和研究防治CIPN药物提供理想的动物模型.方法 大鼠隔日一次腹腔注射给予PTX,采用测痛丝致痛行为学实验考察PTX对大鼠机械性异常性疼痛和机械性痛觉过敏的影响,免疫荧光法检测大鼠后足表皮下神经纤维（intraepidermal nerve fiber,IENF）的形态及数目,电子显微镜检测坐骨神经细胞线粒体的形态及数目.结果 隔日腹腔注射2 mg/kgPTX四次对SD大鼠的体重增长无明显影响;给予PTX后,初始体重为200 g的大鼠在34 d的实验周期内未观察到机械性异常性疼痛,仅在第17天出现了一次机械性痛觉过敏;而初始体重为400 g的大鼠则在第17天表现出了机械性异常性疼痛,第8-26天表现出了机械性痛觉过敏,免疫荧光显示PTX处理组大鼠后足表皮下IENF断裂,IENF密度显著降低,电镜观察可见空泡变性的异常线粒体的比例升高,PTX处理组大鼠表现出明显的外周神经病变.结论 初始体重400 g的SD大鼠对PTX所致的外周神经病变较敏感,适合作为PTX所致外周神经病变的模型动物.     

糖尿病周围神经病变患者生活质量调查研究

目的:探讨糖尿病周围神经病变患者生活质量现状和影响因素.方法:采用自编问卷、抑郁自评量表(SDS)、焦虑自评量表(SAS)、社会支持评定量表(SSRS)、匹兹堡睡眠质量指数问卷(PSQI)和汉化版简明健康调查表(SF-36)量表对2010年10月～2012年10月在我院内分泌科住院治疗的50例糖尿病周围神经病变患者和同期50例在我院健康体检者进行测评,采用SPSS16.0软件进行分析找出糖尿病周围神经病变患者生活质量现状和影响因素.结果:糖尿病周围神经病变患者的生活质量明显低于健康体检者,有显著性差异(P＜0.05).多元线性逐步回归分析发现:文化程度高、患者对疾病了解多、社会支持评定量表总分高与糖尿病周围神经病变患者生活质量正相关,而慢性并发症种类多、有睡眠问题、焦虑抑郁标准分高与糖尿病周围神经病变患者生活质量负相关.结论:糖尿病周围神经病变患者生活质量较低,其生活质量受多方面因素的影响,我们应该采取针对性的干预措施来改善患者的生活质量.     

Electrophysiological Follow-Up of Patients with Chronic Peripheral Neuropathy Induced by Occupational Intoxication with n-Hexane

The aim of this study is to characterize and dynamically monitor the progress of peripheral neuropathy induced by n-hexane by electromyography and nerve conduction velocity (NCV-EMG). Twenty-five patients with n-hexane poisoning from an electronic company were investigated in the year 2009. The occupational history of these workers was collected, and toxic substance exposure was identified. Neurologic inspection and regular NCV-EMG inspection were performed for all patients upon hospital admission and after 3, 6, and 12 months of treatment. NCV-EMG results shown that patients with n-hexane poisoning have simultaneous damage on motor and sensory nerves, of which sensory nerve damage was more severe. Motor nerves of the lower limbs were severe damaged than those of the upper limbs; whereas injury of sensory nerve in the upper limbs was more severe than that of the lower limbs. After treatment, clinical signs and symptoms of the patients were significantly improved. NCV-EMG result showed a delayed worsening at 3 months then gradually recovered after 12 months. Recovery of the motor nerve was better compared with sensory nerve, with upper limbs faster than that of the lower limbs.     

降纤酶联合甲钴胺治疗糖尿病周围神经病变的研究

目的 观察降纤酶联合甲钴胺治疗糖尿病周围神经病变的临床疗效.方法 选择60例糖尿病合并周围神经病变患者,随机分成治疗组和对照组各30例,治疗组用降纤酶首次剂量为10 u,第2天后改为5 u,每天1次,连续2周;同时应用甲钴胺500 μg肌肉注射,每天1次,连续2周.对照组用甲钴胺500 μg肌肉注射,每天1次,连续2周.两组进行疗效比较.结果 治疗2周后两组神经症状与检查评分均明显下降,但以治疗组下降显著,治疗后两组平均评分差异有统计学意义(P＜0.01).结论 降纤酶联合甲钴胺治疗糖尿病周围神经病变有较好的疗效.     

Corneal Confocal Microscopy Detects Small Fibre Neuropathy in Patients with Upper Gastrointestinal Cancer and Nerve Regeneration in Chemotherapy Induced Peripheral Neuropathy

There are multiple neurological complications of cancer and its treatment. This study assessed the utility of the novel non-invasive ophthalmic technique of corneal confocal microscopy in identifying neuropathy in patients with upper gastrointestinal cancer before and after platinum based chemotherapy. In this study, 21 subjects with upper gastrointestinal (oesophageal or gastric) cancer and 21 healthy control subjects underwent assessment of neuropathy using the neuropathy disability score, quantitative sensory testing for vibration perception threshold, warm and cold sensation thresholds, cold and heat induced pain thresholds, nerve conduction studies and corneal confocal microscopy. Patients with gastro-oesophageal cancer had higher heat induced pain (P = 0.04) and warm sensation (P = 0.03) thresholds with a significantly reduced sural sensory (P<0.01) and peroneal motor (P<0.01) nerve conduction velocity, corneal nerve fibre density (CNFD), nerve branch density (CNBD) and nerve fibre length (CNFL) (P<0.0001). Furthermore, CNFD correlated significantly with the time from presentation with symptoms to commencing chemotherapy (r = -0.54, P = 0.02), and CNFL (r = -0.8, P<0.0001) and CNBD (r = 0.63, P = 0.003) were related to the severity of lymph node involvement. After the 3^rd cycle of chemotherapy, there was no change in any measure of neuropathy, except for a significant increase in CNFL (P = 0.003). Corneal confocal microscopy detects a small fibre neuropathy in this cohort of patients with upper gastrointestinal cancer, which was related to disease severity. Furthermore, the increase in CNFL after the chemotherapy may indicate nerve regeneration.