Recommendations for the examination of peripheral nerve biopsies

 Peripheral nerve biopsy is now an established, valuable investigative procedure, but as it can give rise to significant residual symptoms it should only be undertaken after careful consideration of the indications and with informed consent from the patient. Nerve biopsies should only be processed and evaluated in a laboratory with the relevant particular expertise. It is generally recommended that a sural nerve biopsy be performed in combination with a muscle biopsy but not vice versa (muscle biopsies together with a nerve biopsy). Nerve biopsy is not the only means of sampling peripheral nerve tissue to study the peripheral nervous system. Examination of the innervation of the skin may be informative. The same is likely to be true for motor point muscle biopsy. Nerve biopsy is mainly used for morphology although molecular genetic techniques using fresh or archival nerve biopsies are increasingly available. Chemical analysis is undertaken mainly for research purposes. Received: 10 June 1997 / Accepted: 29 October 1997     

中国Leber遗传性视神经病变G11696A突变两个家系分析

目的对两个中国Leber遗传性视神经病变(Leber’shereditary optic neuropathy,LHON)家系的临床和分子遗传学特征进行分析。方法眼科临床检查发现在这两个家系中只有先证者1人出现视力障碍,发病年龄分别为10岁和17岁。对这两个家系先证者使用24对有部分重叠的引物进行线粒体DNA(mitochondrial DNA,mtDNA)全序列扩增分析。结果没有发现mtDNAG11778A、G3460A和T14484C3个常见的突变位点,而发现了与LHON相关的ND4G11196A同质性突变位点的存在,在167名正常对照只发现1例G11696A突变。结论线粒体DNA全序列分析发现两个家系呈现独特的mtDNA多态性,都属于东亚单体型D4。不完全外显率和正常对照频率(1/167)表明G11696A突变本身不足以导致LHON的发生,说明其它因素在这两个LHON家系的表型表达中也起一定的作用。在这些家系mtDNA中缺乏影响重要功能突变位点的存在,排除了线粒体背景对LHON临床表型的影响。因此,核修饰基因、环境因素可能对两个中国G11696A突变家系的外显率和发病严重程度起促进作用。     

Trophic action of pharmacological substances with a guanidine group on mouse neuroblastoma cells and chick ganglionic neurons in culture

A series of substances (designated CTQ compounds) with a guanidine group have been synthesized and tested for their ability to promote neuronal survival and neurite outgrowth. Mouse neuroblastoma clonal cell lines grown in serum-containing medium for 10 days as well as primary cultures of embryonic chicken ganglion neurons grown in serum-free defined medium for 1 or 2 days have been used for the experiments. Among the various CTQ compounds (CTQ1–CTQ20) tested, only CTQ8 exerted positive neurotrophic effects on these peripheral neuronal cells. At a concentration of 10⁻⁴ M, CTQ8 enhanced neuritogenesis of neuroblastoma cells. However, the most striking influence of CTQ8 was its promoting effect (6- to 10-fold) on the survival of chicken ciliary and dorsal root ganglionic neurons at concentrations ranging from 10⁻³ M to 5×10⁻⁴ M.     

Microangiopathy in human diabetic neuropathy

Summary Morphological change of endoneurial and perineurial vessels accompanied severe loss of myelinated axons in peripheral nerves of each of 17 patients with diabetic neuropathy. Vascular mural thickening averaged 18.9±9.9 m² in diabetic capillaries (n=11) vs. 6.9±4.1 m² in controls (n=7). Electron microscopy revealed vigorous endothelial proliferation as well as thickening and reduplication of basal lamina in each instance. Particular attention was paid to vessels which penetrate the perineurium en route to the endoneurial intertitium, since they provide a major portion of the endoneurial blood supply. Luminal narrowing and mural thickening of these vessels was compounded by basal laminar thickening of the perineurium. Fenestrated endoneurial capillary endothelium was noted in one case. Both demyelination and axonal degeneration were observed with intra-axonal glycogen accumulation in some axons. Morphometric analysis revealed extensive myelinated nerve fiber loss in diabetic nerves. These morphological findings emphasize the impact of diabetic microangiopathy on specialized endothelium and suggest that local anatomic factors in the perineurial sheath render the nerve vulnerable to chronic ischemia.Supported in part by the National Institute for Communicative Disorders and Stroke NS-14162 and by the Veterans Administration Research Service     

Trigeminal neuropathy and partial nose destruction

Summary Two cases of trigeminal neuropathy with tissue loss are described, one in a Spillane-Wells syndrome, the other in a Riley-Day syndrome. Although the etiology was different, nose-picking led in both cases to a typical punchedout lesion of the skin and cartilage of nose tip, columella and alae nasi. Reconstruction was performed only in the first case, after resolution of the neuropathy. Reconstruction should not be considered for cases with persistant anaesthesia.Head: M. Lejour     

中药治疗糖尿病微血管病变的研究进展

糖尿病及其并发症病是全世界关注的重大公共卫生问题。糖尿病微血管病变是糖尿病虚损夹血瘀形成的血管并发症,以微循环障碍并伴有透明样物质沉积为基本病理改变特征,糖尿病肾病、糖尿病视网膜病变和糖尿病神经病变最为常见。糖尿病微血管病变可追溯到糖尿病前期,随着糖尿病发生发展动态演进不断加重,需及早干预。临床在降糖、降脂、降压的基础治疗上,多选择抗氧化应激、抗炎、改善微循环和抗血管新生的药物治疗糖尿病微血管并发症。糖尿病微血管病变属于中医“络病”的概念,中药治疗糖尿病微血管病变的核心是在降糖的基础上保护“孙络-微血管”,组方多为补气滋阴、清热活血药味配伍而成。该文基于糖尿病微血管病变的中西医认识及治疗原则,简要概述针对不同证型治疗糖尿病微血管病变的常用方剂,如白虎加人参汤、玉液汤、四妙勇安汤、葛根芩连汤、六味地黄丸及一些现代制剂,同时概述方剂常用药味,如人参、黄芪、地黄、枸杞子、三七、丹参、金银花、葛根的研究进展,以期为中药治疗糖尿病微血管病变提供临床依据和理论指导。     

黄芪桂枝五物汤加减对糖尿病大鼠坐骨神经细胞凋亡相关Bax和Caspase-12的影响

目的 研究黄芪桂枝五物汤加减对糖尿病大鼠坐骨神经细胞凋亡相关B细胞淋巴瘤-2相关X蛋白（Bax）和胱天蛋白酶-12（Caspase-12）蛋白与mRNA表达的影响,以探究黄芪桂枝五物汤加减治疗糖尿病周围神经病变的作用机制。方法 选用动物实验方法进行研究,将60只雄性SD大鼠通过高糖高脂饲料喂养联合链尿佐菌素（STZ）腹腔注射诱导成糖尿病大鼠动物模型,连续3 d随机血糖≥16.7 mmol·L^-1者为糖尿病大鼠造模成功,将48只造模成功的糖尿病大鼠随机分为模型组、α-硫辛酸组（0.026 8 g·kg^-1·d^-1）、中药高、低剂量组（2.5、1.25 g·kg^-1·d^-1）,每组各12只,并设正常组10只。监测大鼠体质量和随机血糖水平;干预16周末通过Key point肌电采集系统检测大鼠坐骨神经传导速度;分别通过蛋白免疫印迹法（Western blot）和实时荧光定量聚合酶链式反应（Real-time PCR）检测大鼠坐骨神经中Bax和Caspase-12蛋白与mRNA的表达。结果 与正常组比较,模型组大鼠体质量显著下降（P<0.01）,随机血糖水平显著升高（P<0.01）;干预16周,与模型组比较,中药高剂量组大鼠体质量明显升高（P<0.05）,其他给药组体质量变化差异无统计学意义;各给药组随机血糖水平均显著降低（P<0.01）。与正常组比较,干预16周,模型组大鼠运动和感觉神经传导速度显著降低（P<0.01）;与模型组比较,各给药组大鼠运动和感觉神经传导速度均明显升高（P<0.05,P<0.01）。与正常组比较,模型组大鼠坐骨神经Bax和Caspase-12蛋白表达显著升高（P<0.01）;与模型组比较,各给药组大鼠坐骨神经Bax和Caspase-12蛋白表达均显著降低（P<0.01）。与正常组比较,模型组大鼠坐骨神经Bax和Caspase-12 mRNA表达显著升高（P<0.01）;与模型组比较,α-硫辛酸组、中药高剂量组大鼠坐骨神经Bax mRNA表达明显降低（P<0.05,P<0.01）,中药低剂量组坐骨神经Bax mRNA表达降低有下降趋势;各给药组大鼠坐骨神经Caspase-12 mRNA表达显著降低（P<0.01）。结论 黄芪桂枝五物汤加减可能通过抑制坐骨神经细胞凋亡来改善和修复糖尿病大鼠坐骨神经损伤。     

Vitamin B12 Supplementation in Diabetic Neuropathy: A 1-Year,Randomized, Double-Blind,Placebo-Controlled Trial

Aim: To investigate the effect of normalizing vitamin B12 (B12) levels with oral B12 (methylcobalamin) 1000 μg/day for one year in patients with diabetic neuropathy (DN). Patients and methods: In this prospective, double-blind, placebo-controlled trial, 90 patients with type 2 diabetes on metformin for at least four years and both peripheral and autonomic DN were randomized to an active treatment group (n = 44) receiving B12 and a control group (n = 46) receiving a placebo. All patients had B12 levels less than 400 pmol/L. Subjects underwent measurements of sural nerve conduction velocity (SNCV), sural nerve action potential (amplitude) (SNAP), and vibration perception threshold (VPT), and they performed cardiovascular autonomic reflex tests (CARTs: mean circular resultant (MCR), Valsalva test, postural index, and orthostatic hypotension). Sudomotor function was assessed with the SUDOSCAN that measures electrochemical skin conductance in hands and feet (ESCH and ESCF, respectively). We also used the Michigan Neuropathy Screening Instrument Questionnaire and Examination (MNSIQ and MNSIE, respectively) and questionnaires to evaluate quality of life (QoL) and level of pain (pain score). Results: B12 levels increased from 232.0 ± 71.8 at baseline to 776.7 ± 242.3 pmol/L at follow-up, p < 0.0001, in the active group but not in the control group. VPT, MNSIQ, QoL, pain score, SNCV, SNAP, and ESCF significantly improved in the active group (p < 0.001, p = 0.002, p < 0.0001, p < 0.000, p < 0.0001, p < 0.0001, and p = 0.014, respectively), whereas CARTS and MNSIE improved but not significantly. MCR, MNSIQ, SNCV, SNAP, and pain score significantly deteriorated in the control group (p = 0.025, p = 0.017, p = 0.045, p < 0.0001, and p < 0.0001, respectively). Conclusions: The treatment of patients with DN with 1 mg of oral methylcobalamin for twelve months increased plasma B12 levels and improved all neurophysiological parameters, sudomotor function, pain score, and QoL, but it did not improve CARTS and MNSIE.     

显微外科技术治疗周围神经嵌压症

目的 :为探讨显微外科技术治疗周围神经嵌压症的疗效。方法 :采用显微外科技术对各部位周围神经嵌压症 2 5例进行神经内外松解术。结果 :2 5例周围神经嵌压症患者术后症状、体征及肌电图检查均较术前明显改善 ,疗效满意。结论 :显微外科技术是治疗周围神经嵌压症的一种有效方法。     

银杏黄酮甙和甲基B_(12)联合治疗糖尿病周围神经病变的疗效观察

目的　探讨银杏黄酮甙和甲基B12 对糖尿病周围病变的治疗效果。方法　将 14 9例糖尿病周围神经病变患者随机分为 4组 ,分别为常规治疗组 (对照组 )、银杏黄酮甙组 (第 1组 )、甲基B12 组 (第 2组 )、银杏黄酮甙与甲基B12 联合组(第 3组 )。疗程为 8周。观察治疗前后自觉症状、腱反射和神经传导速度。结果　第 3组总有效率为 95 % ,显著高于对照组 (17% ) (P <0 .0 0 5 )。第 1组和第 2组 ,总有效率分别为 6 9%和 72 % ,与对照组比较均有显著差异 (P <0 .0 1)。第 3组神经传导速度治疗后较冶疗前显著改善 (P <0 .0 1) ,而且显著优于对照组 (P <0 .0 1)、第 1组 (P <0 .0 5 )和第 2组 (P <0 .0 5 )。结论　银杏黄酮甙和甲基B12 联合治疗糖尿病周围神经病变较单独应用更为有效。