外周神经阻滞麻醉在糖尿病周围神经病变患者中应用的研究进展

外周神经阻滞麻醉的合理应用可避免全身麻醉或椎管内麻醉相关并发症,促进患者康复,其在糖尿病周围神经病变(diabetic peripheral neuropathy, DPN)患者中的应用存在一定优势并日益受到重视。但由于DPN患者的外周神经已存在基础病变,应用外周神经阻滞麻醉是否增加神经损伤风险引起广泛关注。本文将对外周神经阻滞麻醉在DPN患者中的优势、麻醉实施、局麻药浓度和佐剂的选择、降低麻醉相关并发症风险等方面内容进行阐述,旨在为临床实践提供依据,提高外周神经阻滞麻醉在DPN患者中应用的安全性。     

Ulnar Neuropathy With Normal Electrodiagnosis and Abnormal Nerve Ultrasound

Yoon JS, Walker FO, Cartwright MS. Ulnar neuropathy with normal electrodiagnosis and abnormal nerve ultrasound.Ulnar neuropathy at the elbow (UNE) is the second most common entrapment neuropathy. It is diagnosed with electrodiagnostic studies, but they can yield false-negative results. Ultrasound was used to examine 4 patients with UNE and negative electrodiagnostic findings, and it showed ulnar nerve enlargement near the elbow in all cases, with a mean cross-sectional area of 20.1mm². This indicates that ultrasound may be a useful tool for assessing those with UNE symptoms and normal electrodiagnostic findings.     

Increased Axonal Regeneration and Swellings in Intraepidermal Nerve Fibers Characterize Painful Phenotypes of Diabetic Neuropathy

We examined changes in intraepidermal nerve fibers (IENFs) to differentiate patients with diabetic neuropathy (DN) and diabetic neuropathic pain (DN-P) from those with DN without pain (DN-NOP). Punch skin biopsies were collected from the proximal thigh (PT) and distal leg (DL) of normal subjects, patients with type 2 diabetes without evidence of DN (DM), or DN-P and DN-NOP patients. Protein gene product 9.5-positive (PGP+) immunohistochemistry was used to quantify total IENF, and growth-associated protein 43 (GAP43) for regenerating IENF. Compared to normal subjects and patients with type 2 diabetes without evidence of DN, both DN-P and DN-NOP have reduced PGP+ IENF densities in DL and PT. Although GAP43+ IENF densities were also reduced in DL for both DN-P and DN-NOP, the GAP43+ IENF densities in PT of DN-P remained at the control levels. Higher GAP43/PGP ratios were detected in DN-P compared to DN-NOP in the DL and PT. In parallel, increased numbers of axonal swellings per PGP+ fiber (axonal swelling/PGP) were detected in DN-P compared to normal subjects, patients with type 2 diabetes without evidence of DN, and DN-NOP in the DL. These axonal swellings were positive for tropomyosin-receptor-kinase A and substance P, suggesting that they are associated with nociception.PerspectiveAmong patients with DN, the ratios of GAP43/PGP and axonal swelling/PGP are likely to differentiate painful from painless phenotypes.     

Efficacy and Safety of Lacosamide in Painful Diabetic Neuropathy

OBJECTIVE

To evaluate efficacy and safety of lacosamide compared with placebo in painful diabetic polyneuropathy.

RESEARCH DESIGN AND METHODS

Diabetic patients with at least moderate neuropathic pain were randomized to placebo or lacosamide 400 (in a slow or standard titration) or 600 mg/day over 6-week titration and 12-week maintenance periods. Primary efficacy criterion was intra-individual change in average daily Numeric Pain Rating Scale score from baseline to the last 4 weeks.

RESULTS

For the primary end point, pain reduction was numerically but not statistically greater with lacosamide compared with placebo (400 mg/day, P = 0.12; 600 mg/day, P = 0.18). Both doses were significantly more effective compared with placebo over the titration (P = 0.03, P = 0.006), maintenance (P = 0.01, P = 0.005), and entire treatment periods (P = 0.03, P = 0.02). Safety profiles between titration schemes were similar.

CONCLUSIONS

Lacosamide reduced neuropathic pain and was well tolerated in diabetic patients, but the primary efficacy criterion was not met, possibly due to an increased placebo response over the last 4 weeks.Up to one in four patients with diabetes may be affected by chronic diabetic painful neuropathy (DPN) (1,2) and suffer substantial morbidity and impaired quality of life (3). Because the current treatment options are limited, there is continued need for new therapeutic approaches (3,4). Lacosamide is an anticonvulsant with a unique mode of action, selectively enhancing slow inactivation of voltage-gated sodium channels (5–8). This trial was one of three similarly designed placebo-controlled, parallel-group trials to evaluate the efficacy of lacosamide in DPN (9,10) using 400 mg/day (two titration schemes) and 600 mg/day.     

银杏达莫对糖尿病周围神经病变患者神经传导速度的影响

目的 观察银杏达莫对糖尿病周围神经病变（DPN）患者神经症状、体征及神经传导速度的影响。方法 将60例DPN患者随机分为观察组和对照组各30例．对照组采用DPN的常规治疗．观察组在对照组用药基础上加用银杏达莫注射液20ml／d静脉滴注，连用4周。治疗前后观察患者的神经症状和体征，测定四肢感觉神经和运动神经传导速度，并比较其变化。结果 治疗后，观察组患者的神经症状和体征明显改善，神经传导速度明显增快，与治疗前比较有非常显著性差异（P〈0．01）；与对照组比较亦有非常显著性差异（P〈0．01）。结论 银杏达莫可明显改善DPN患者的临床症状和体征，并能提高神经传导速度。     

Contemporary Insights into Painful Diabetic Neuropathy and Treatment with Spinal Cord Stimulation

A substantial body of literature is available on the natural history of diabetes, but much less is understood of the natural history of painful diabetic peripheral neuropathy (PDPN), a pervasive and costly complication of diabetes mellitus. Multiple mechanisms have been proposed, including polyol pathway activation, advanced glycosylation end-product formation, and vasculopathic changes. Nevertheless, specific treatment modalities addressing these basic issues are still lacking. The mainstay of treatment includes pharmacological management with antidepressants, anticonvulsants, and opioids, but these drugs are often limited by unfavorable side-effect profiles. For over 30 years, spinal cord stimulation (SCS) has been used extensively for the management of various chronic neuropathic pain states. In the past decade, interest in the use of SCS for treatment of PDPN has increased. This article reviews pathophysiological mechanisms of PDPN, proposed mechanisms of SCS, and the role of SCS for the treatment of PDPN.     

中老年糖尿病和糖尿病合并神经系疾病患者血液流变性变化

本文报告４６例糖尿病、３５例糖尿病合并神经系疾病的患者和４９例健康者之间的血液流学５项指标及血脂、纤维旦白的对比观察．结果表明糖尿病人与对照组比较，明显处于高粘、高脂状态，尤以糖尿病伴合并症组更为显著．提示对糖尿病合并神经病变者，在降糖、降脂等治疗的同时，当注重疏通微循环，改善血液流变性．     

代谢因素与糖尿病周围神经病的关系

目的：研究糖尿病各种代谢因素和糖尿病周围神经病的关系。方法：将182例2型糖尿病患者根据肌电图和神经传导速度测定的结果分为糖尿病周围神经病大纤维病变（diabetic peripheral neuropathy,DPN）组（66例）和无糖尿病周围神经病大纤维病变组（116例）。分别记录2组患者性别、年龄、糖尿病病程,测量体质量、身高、血压、空腹血糖、餐后2h血糖及血糖化血红蛋白、三酰甘油和高密度脂蛋白胆固醇等指标。结果：糖尿病患者年龄越大（P=0.014）,病程越长（P=0.000）,合并高血压（P=0.003）和体质量指数（BMI）异常（P=0.033）,餐后2h血糖（P=0.046）以及糖化血红蛋白（P=0.008）控制不佳,容易发生糖尿病周围神经病大纤维病变,其中年龄、糖尿病病程、收缩压、血糖化血红蛋白均和下肢腓肠神经感觉波幅呈负相关。Logistic回归分析显示,患者年龄、高血压情况以及餐后2h血糖为糖尿病周围神经病大纤维病变的主要影响因素。结论：糖尿病发病年龄、病程以及血压、BMI和血糖控制水平与糖尿病周围神经病大纤维病变的发生密切相关。     

Exercise-Induced Modulation of Pain in Adults With and Without Painful Diabetic Neuropathy

The purpose of this study was to examine exercise-induced pain modulation in diabetic adults with painful diabetic neuropathy (PDN) compared to diabetic adults without PDN. Eighteen adults diagnosed with type 2 diabetes with and without PDN (mean age of 49 years) completed 2 sessions. During the familiarization session, participants completed questionnaires, were familiarized with the pain testing protocols, and completed maximal isometric contractions. During the exercise session, experimental pain testing was completed before and following exercise consisting of 3 minutes of isometric exercise performed at 25% maximal voluntary contraction. Ratings of perceived exertion and muscle pain were assessed every 30 seconds during exercise. Results indicated that ratings of perceived exertion and muscle pain during exercise were significantly higher (P < .05) for diabetic adults with PDN versus diabetic adults without PDN. Diabetic adults with PDN did not experience changes in thermal pain ratings following exercise, whereas diabetic adults without PDN reported significantly lower pain ratings following exercise. It is concluded that diabetic adults with PDN experienced high levels of muscle pain during exercise and a lack of exercise-induced hypoalgesia following exercise, in comparison to diabetic adults without PDN, who experienced lower levels of muscle pain during exercise and a hypoalgesic response following exercise.PerspectiveVery little research has been conducted examining the impact of exercise on pain modulation in diabetic adults with PDN. This study provides support that adults with PDN exhibit exercise-induced endogenous pain modulatory system dysfunction.     

Small Nerve Fiber Quantification in the Diagnosis of Diabetic Sensorimotor Polyneuropathy: Comparing Corneal Confocal Microscopy With Intraepidermal Nerve Fiber Density

OBJECTIVE

Quantitative assessment of small fiber damage is key to the early diagnosis and assessment of progression or regression of diabetic sensorimotor polyneuropathy (DSPN). Intraepidermal nerve fiber density (IENFD) is the current gold standard, but corneal confocal microscopy (CCM), an in vivo ophthalmic imaging modality, has the potential to be a noninvasive and objective image biomarker for identifying small fiber damage. The purpose of this study was to determine the diagnostic performance of CCM and IENFD by using the current guidelines as the reference standard.

RESEARCH DESIGN AND METHODS

Eighty-nine subjects (26 control subjects and 63 patients with type 1 diabetes), with and without DSPN, underwent a detailed assessment of neuropathy, including CCM and skin biopsy.

RESULTS

Manual and automated corneal nerve fiber density (CNFD) (P < 0.0001), branch density (CNBD) (P < 0.0001) and length (CNFL) (P < 0.0001), and IENFD (P < 0.001) were significantly reduced in patients with diabetes with DSPN compared with control subjects. The area under the receiver operating characteristic curve for identifying DSPN was 0.82 for manual CNFD, 0.80 for automated CNFD, and 0.66 for IENFD, which did not differ significantly (P = 0.14).

CONCLUSIONS

This study shows comparable diagnostic efficiency between CCM and IENFD, providing further support for the clinical utility of CCM as a surrogate end point for DSPN.     

高频脊髓刺激治疗糖尿病神经病变

大约20%的糖尿病患者会出现疼痛性糖尿病神经病变(PND)。本项10kHz脊髓刺激联合常规治疗与单独CMM治疗神经性肢体疼痛(SENZA-PDN)的研究比较了SCS联合CMM与单独CMM治疗难治性PDN的疗效。受试者为患有PND,对加巴喷丁或普瑞巴林耐药,并对至少一种其他类型的镇痛药耐药的患者。治疗开始前对所有受试者进行神经系统检查,包括下肢运动功能、轻触觉和反射。SCS组在硬膜外放置2条经皮导联,给予频率10kHz、脉宽30μs、振幅0.5~3.5mA的SCS治疗。结局指标是治疗3个月时VAS评分提示疼痛缓解50%及以上且神经功能缺损较治疗前无恶化者所占的比例。随访3个月时,5%的CMM组和79%的SCS组受试者达到了主要结局指标(P<0.01)。随访6个月时,CMM组VAS平均评分保持不变,SCS组VAS平均评分改善76.3%。与CMM组相比,SCS组在EQ5D-5LVAS生活质量评分方面有显著改善(P<0.001)。在随访6个月时,CMM组因疼痛引起的睡眠障碍增加了5.3%,而SCS组减少了61.9%。结论:本项针对疼痛性糖尿病下肢神经病变患者的研究发现,与常规治疗相比,联合脊髓刺激可以显著减轻疼痛。     

Quantitative Sensory Testing for Spinal Cord Stimulation in Patients With Chronic Neuropathic Pain

Objective: A prospective pilot study was conducted, attempting to identify objective tests that would help clinicians to assess the efficacy of spinal cord stimulation (SCS) trial preceding permanent device implantation. Setting: Four university hospitals in the United States and Israel. Participants: Thirteen patients with radicular leg pain due to failed back surgery syndrome (FBSS) or leg pain due to complex regional pain syndrome (CRPS) who were candidates for SCS. Methods: Participants underwent a series of quantitative sensory tests prior to, and seven days after the initiation of SCS trial. These tests included: vibration threshold (conducted using the VSA 3000; Medoc Inc., Ramat Ishay, Israel), cold threshold, warm threshold, heat pain threshold, phasic heat pain threshold, tonic heat pain threshold (conducted using the TSA 2001; Medoc Inc.), and electrical pain tolerance at 5, 250 and 2000 Hz (administered using the NerveScan^TM 2000; Neurotron, Inc., Baltimore, MD, U.S.A.). Results: Useful data were obtained from 12 patients. The results of the vibration threshold and the tolerance to electrical stimulation at 5 and 250 Hz changed with an SCS trial. These results also correlated with the decision regarding the permanent implantation, which was made independently of them. In contrast, the results of thermal thresholds and tolerance to electrical stimulation at 2000 Hz tests did not change with the SCS trial. Conclusions: Our findings, which agree with those of a few other studies, suggest that the vibration threshold and the tolerance to electrical stimulation at 5 and 250 Hz tests can assist the clinician to select the right patients for permanent stimulation.     

Quantitative Sensory Testing of Neuropathic Pain Patients: Potential Mechanistic and Therapeutic Implications

Quantitative sensory testing (QST) is a widely accepted tool to investigate somatosensory changes in pain patients. Many different protocols have been developed in clinical pain research within recent years. In this review, we provide an overview of QST and tested neuroanatomical pathways, including peripheral and central structures. Based on research studies using animal and human surrogate models of neuropathic pain, possible underlying mechanisms of chronic pain are discussed. Clinically, QST may be useful for 1) the identification of subgroups of patients with different underlying pain mechanisms; 2) prediction of therapeutic outcomes; and 3) quantification of therapeutic interventions in pain therapy. Combined with sensory mapping, QST may provide useful information on the site of neural damage and on mechanisms of positive and negative somatosensory abnormalities. The use of QST in individual patients for diagnostic purposes leading to individualized therapy is an interesting concept, but needs further validation.     

高频超声对Ⅱ型糖尿病周围神经病变患者腓总神经的临床观察

目的 探讨高频超声观察Ⅱ型糖尿病周围神经病变患者腓总神经的临床价值。方法 选取62例2型糖尿病患者,分为周围神经病变组32例和无周围神经病变组30例,并选择同期28例非糖尿病患者作为对照组,应用高频超声观察各组腓管处腓总神经图像变化,测量并比较腓总神经前后径、横径及横截面积,并结合神经电生理检查进行相关性分析。结果 周围神经病变组腓总神经前后径、横径及横截面积较无周围神经病变组和对照组均增大,差异均有统计学意义（均P＜0.05）。糖尿病伴周围神经病变组患者腓总神经的横截面积与腓总神经感觉传导速度呈显著负相关（r=-0.552,P＜0.01）。结论 高频超声能显示糖尿病合并周围神经病变患者腓总神经的异常改变,为临床诊断提供客观依据。     

依达拉奉对糖尿病周围神经病变大鼠坐骨神经的保护作用

目的:研究依达拉奉对糖尿病周围神经病变(DPN)大鼠坐骨神经的保护作用。方法:SD大鼠80只,采用链脲佐菌素(STZ)一次性腹腔注射诱导建立DPN模型,随机分为对照组和治疗组,治疗组每天给予3 mg/kg依达拉奉腹腔注射4周,观察摆尾温度阈值(TTT)、坐骨神经运动神经传导速度(MCV)、感觉神经传导速度(SCV)、神经形态和坐骨神经中一氧化氮(NO)含量、丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性。结果:对照组大鼠TTT升高,MCV和SCV减慢(P<0.01),形态学明显异常,NO、MDA含量明显增多,SOD活性显著降低(P<0.01)。治疗组与对照组比较TTT明显降低,MCV和SCV明显加快,形态学明显改善,NO、MDA含量明显减少,SOD活性显著增高(P<0.01)。结论:依达拉奉可降低DPN大鼠坐骨神经损伤。     

A Randomized,Controlled Trial of Oxycodone Versus Placebo in Patients With PostHerpetic Neuralgia and Painful Diabetic Neuropathy Treated With Pregabalin

The aim of this randomized double-blind, placebo-controlled, parallel-group study was to evaluate the efficacy, safety, and tolerability of pregabalin in combination with oxycodone or placebo, in patients with either postherpetic neuralgia (PHN) or painful diabetic neuropathy (PDN). After a 7-day washout period, 62 patients were randomized to receive either oxycodone mixture 10 mg/day or placebo mixture for 1 week. Patients were then started on open-label pregabalin (75, 150, 300 and 600 mg/day) according to a forced titration dosing regimen, while continuing the same dosage of oxycodone or placebo for 4 weeks. The primary efficacy measure was a decrease in the pain-intensity score of at least 2cm and a pain score <4cm measured using a 10-cm visual analogue scale (VAS) following pregabalin dosage escalation and treatment for 4 weeks. Secondary efficacy measures included sleep interference and the Neuropathic Pain Scale. There were similar levels of overall efficacy between pregabalin/oxycodone and pregabalin/placebo groups in relieving PHN and PDN related pain.PerspectivePeripheral neuropathic pain presents commonly in clinical practice, and 2 of its most prevalent types are PHN and PDN. Currently available treatments provide some degree of pain relief in ～40-60% of patients, leaving the remainder with unremitting pain. Although this study supports the effectiveness of pregabalin in the treatment of PHN or PDN, it also shows that the addition of a low dose of oxycodone at 10mg/day does not enhance the pain-relieving effects of pregabalin.     

Retinal Nerve Fiber Layer Segmentation on FD-OCT Scans of Normal Subjects and Glaucoma Patients

Automated measurements of the retinal nerve fiber layer thickness on circular OCT B-Scans provide physicians additional parameters for glaucoma diagnosis. We propose a novel retinal nerve fiber layer segmentation algorithm for frequency domain data that can be applied on scans from both normal healthy subjects, as well as glaucoma patients, using the same set of parameters. In addition, the algorithm remains almost unaffected by image quality. The main part of the segmentation process is based on the minimization of an energy function consisting of gradient and local smoothing terms. A quantitative evaluation comparing the automated segmentation results to manually corrected segmentations from three reviewers is performed. A total of 72 scans from glaucoma patients and 132 scans from normal subjects, all from different persons, composed the database for the evaluation of the segmentation algorithm. A mean absolute error per A-Scan of 2.9 μm was achieved on glaucomatous eyes, and 3.6 μm on healthy eyes. The mean absolute segmentation error over all A-Scans lies below 10 μm on 95.1% of the images. Thus our approach provides a reliable tool for extracting diagnostic relevant parameters from OCT B-Scans for glaucoma diagnosis.