Intraepidermal nerve fibre density, quantitative sensory testing and nerve conduction studies in a patient material with symptoms and signs of sensory polyneuropathy

Small diameter nerve fibre (SDNF) neuropathy is an axonal sensory neuropathy affecting unmyelinated (C) and thin myelinated (A-delta) fibres. We have evaluated 75 patients with symptoms and signs suggesting SDNF dysfunction with or without symptoms and signs of co-existing large diameter nerve fibre involvement. The patients were examined clinically and underwent skin biopsy, quantitative sensory testing (QST) and nerve conduction studies (NCS). The purpose of this study was to compare the relationship between the different methods and in particular measurements of thermal thresholds and intraepidermal nerve fibre (IENF) density in the same site of the distal leg. The main subdivision of the patient material was made according to the overall NCS pattern. Patients with normal NCS (38) had 6.4 +/- 3.8 and patients with abnormal NCS (37) had 4.4 +/- 3.4 IENF per mm (P = 0.02). Limen (difference between warm and cold perception thresholds) was significantly higher (more abnormal) in those with abnormal than in those with normal NCS (22.1 +/- 9.1 vs. 13.4 +/- 5.6, P < 0.0001). Cold perception threshold was more abnormal (P < 0.0001) than warm perception threshold (P = 0.002). Correlation between IENF and QST was statistically significant only when NCS was abnormal, and thus dependent of a more severe neuropathic process in SDNFs.     

Value of repeated measures of nerve conduction and quantitative sensory testing in a diabetic neuropathy trial

Conduct of a large, multicenter trial of the aldose reductase inhibitor zenarestat provided data on the reproducibility of multiple electrophysiologic (nerve conduction studies, NCS) and quantitative sensory (QST) tests. Baseline and 12-month electrophysiologic data from approximately 1100 patients at multiple centers were available for analysis. Intersite variability contributed minimally to overall test variance. All NCS tests were highly reproducible. Cool thermal and vibration QST thresholds, as measured by CASE IV instrumentation, were also highly reproducible. Intersubject variance accounted for the majority of variance for all parameters measured. Repeating NCS and QST measures decreased sample sizes needed to show statistical significance. Consideration of these observations, particularly with regard to QST, should aid in the design of future clinical trials investigating neuropathy.     

Aspects of peripheral nerve involvement in patients with treated hypothyroidism

Background:  We studied involvement of large and small nerve fibres in patients with hypothyroidism and symptoms and signs of polyneuropathy.
Methods:  Sixteen patients with established diagnosis of hypothyroidism were extracted from a patient population participating in a 'polyneuropathy study'. In addition, seven patients with other additional potential causes of polyneuropathy than hypothyroidism were investigated. The patients underwent neurological examination, routine blood tests, nerve conduction studies (NCS), quantitative sensory testing (QST) and skin biopsies with assessment of intraepidermal nerve fibre (IENF) density.
Results:  Sixty-three per cent of the patients with 'pure' hypothyroidism had abnormalities on NCS, 25% had reduced IENF density and 31% had abnormalities on QST. Four patients (25%) met criteria for small fibre polyneuropathy, the other (75%) were classified as having mixed fibre polyneuropathy. There were no differences in the amount of abnormalities on NCS, QST and skin biopsy between patients with hypothyroidism and those with hypothyroidism and other potential causes of polyneuropathy.
Conclusions:  The majority of patients with hypothyroidism had involvement of both large and small nerve fibres. However, some patients had isolated small fibre polyneuropathy. Patients with 'pure' hypothyroidism had essentially the same degree of peripheral nerve fibre involvement as those with other additional causes of polyneuropathy.     

Intraepidermal nerve fiber density as a marker of early diabetic neuropathy

The purpose of the study was to reliably identify an early stage of diabetic polyneuropathy (DPN) by measuring injury to epidermal nerve fibers. We compared intraepidermal nerve fiber density (IENFD) at the ankle and thigh of 29 diabetic subjects who had no clinical or electrophysiological evidence of small- or large-fiber neuropathy to that of 84 healthy controls. The mean ankle IENFD of diabetic subjects was 9.1+/-5.0 mm and that of controls, 13.0+/-4.8 mm (P<0.001). The thigh IENFD did not differ significantly. The IENFD ratio (thigh IENFD divided by ankle IENFD) was 2.39+/-1.30 in diabetic subjects and 1.77+/-0.58 in controls (P<0.001), indicating a length-dependent reduction of IENFD in diabetics. Ankle IENFD remained significantly lower and the IENFD ratio higher in diabetic subjects after adjusting for age. Two subjects had parasympathetic dysfunction, two had retinopathy, and two early nephropathy. Age, height, weight, duration of diabetes, and average HbA1c did not influence IENFD among diabetic subjects. We used receiver operating characteristic (ROC) curves to describe and compare the utility of various threshold values of ankle IENFD and IENFD ratio for the diagnosis of early DPN. The sensitivity and specificity of diagnosing DPN using ankle IENFD of less than 10 mm were 72.4% and 76.2%, respectively. Thus, asymptomatic diabetics have a measurable, length-dependent reduction of distal epidermal nerves. Analogous to microalbuminuria in diabetic nephropathy, reliable identification and quantitation of nascent diabetic neuropathy may have potential therapeutic implications.     

Correlation of vibratory quantitative sensory testing and nerve conduction studies in patients with diabetes

Monitoring the course of diabetic peripheral neuropathy (DPN) remains a challenge. Besides clinical examination, nerve conduction studies (NCS) and quantitative sensory testing (QST) are the most commonly used methods for evaluating peripheral nerve function in clinical trials and population studies. In this study the correlation between vibratory QST and NCS was determined. Patients (N = 227) with diabetes mellitus participated in this multicenter, single-visit, cross-sectional study. QST of vibration measured with the CASE IV system was compared with a composite score of peroneal motor and tibial motor NCS and with individual attributes of peroneal, tibial, and sural nerves. The correlation between QST and composite score of NCS was 0.234 (Pearson correlation coefficient, P = 0.001). The correlations between QST and individual attributes of NCS ranged from 0.189 to 0.480 (Pearson correlation coefficients, P < 0.001). The low to moderate correlation between QST and NCS suggests that these tests cannot replace each other but are complementary.     

Tactile direction discrimination and vibration detection in diabetic neuropathy

Löken LS, Lundblad LC, Elam M, Olausson HW. Tactile direction discrimination and vibration detection in diabetic neuropathy. Acta Neurol Scand: 2010: 121: 302–308.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objective – To evaluate the clinical usefulness of quantitative testing of tactile direction discrimination (TDD) in patients with diabetic neuropathy. Materials and methods – TDD and vibration detection were examined on the dorsum of the feet in 43 patients with type 1 diabetes mellitus and clinical signs and symptoms indicating mild neuropathy, and abnormal results for neurography, temperature detection, or heart rate variability. Test–retest examination of TDD was performed in nine of the patients. Results – Twenty‐six of the patients had abnormal TDD (sensitivity 0.60) and 20 had abnormal vibration detection (sensitivity 0.46). Ten of the patients had abnormal TDD and normal vibration detection. Four of the patients had abnormal vibration detection and normal TDD. Test–retest examination of TDD showed a high degree of reproducibility (r = 0.87). Conclusion – TDD seems more useful than vibration detection in examination of diabetic neuropathy.     

Carpal tunnel syndrome with normal nerve conduction studies

The utility of electrodiagnostic testing in the evaluation of carpal tunnel syndrome (CTS) has been questioned. We studied patients who met the clinical criteria for CTS and compared patients who had normal nerve conduction studies (NCS) with patients who had abnormal NCS. We found that 25% of the CTS patients without confounding neurologic disorders had normal NCS with median palmar nerve stimulation. Patients with abnormal NCS were older and heavier and had more clinical features of CTS. NCS results could not be predicted accurately from clinical features by use of logistic regression models. This was especially true in clinically borderline cases. NCS did not predict the outcome of conservative management. We concluded that NCS provide independent information in the evaluation of suspected CTS, especially when fewer clinical criteria are present, but that NCS are not helpful in predicting the outcome of nonsurgical management.     

Sensory and mixed nerve conduction studies in the evaluation of ulnar neuropathy at the elbow

The relative sensitivities of sensory, mixed nerve, and motor conduction studies in assessing ulnar neuropathy at the elbow have not yet been established. Using surface electrodes, we performed conduction studies across the elbow segment in 43 patients with symptoms referable to the ulnar nerve and 40 control subjects. Segmental slowing of motor conduction localized the lesion to the elbow in 14 of 21 patients (67%) with clear evidence of ulnar neuropathy on physical examination but only in 2 of 22 (9%) with subtle or no physical examination abnormalities. The diagnostic yield was increased by the finding of segmental slowing of sensory or mixed nerve conduction across the elbow to 86% and 68%, respectively, for each of the groups. We conclude that surface-recorded sensory and mixed nerve conduction studies appear to be more sensitive than motor studies in the electrodiagnosis of ulnar neuropathy at the elbow and are especially valuable in patients with subtle clinical involvement. © 1994 John Wiley & Sons, Inc.     

Large electrodes improve nerve conduction repeatability in controls as well as in patients with diabetic neuropathy

Recording site is an important cause of variability of compound muscle action potential (CMAP) and conduction parameters, which can be reduced by using large electrodes. Repeatability of CMAP and conduction parameters of conventional and large electrodes was compared in 16 controls and 17 diabetic neuropathic patients, using defined recording sites linked to anatomical landmarks. Right-sided median, peroneal, and tibial nerves were investigated twice by the same examiner, with a 1–2 week interval. Compared to previous studies, conventional electrodes on strictly defined recording sites resulted in better repeatability: intraindividual coefficients of variation (CV) varied between 4% and 14.4% for all parameters. CV of conduction parameters, not published previously, was smaller than CV of CMAP parameters. The use of large electrodes improved repeatability further: large electrodes resulted in substantially smaller CV for duration, amplitude, area, and changes of amplitude and area over a length of nerve, which were reduced by 10%, 31%, 29%, 27%, and 16%, respectively. Patients had higher CV than controls; large electrodes reduced patient CV more than control CV, resulting in less contrast between groups. Strictly defined recording sites and large electrodes improve repeatability of motor conduction studies to relevant degrees: all CMAP and conduction parameters are suitable for longitudinal studies of neuropathic patients. © 1996 John Wiley & Sons, Inc.     

定量感觉检查对糖尿病周围神经病的早期诊断价值

目的　探讨定量感觉检查(QST)对糖尿病周围神经病的早期诊断价值。方法　对46例糖尿病 患者神经传导速度(NCV)和QST进行检测,并将其结果进行对比研究。结果　46例糖尿病患者中NCV异常 率为72.8%(35/46),NCV诊断糖尿病周围神经病32例(69.6%);QST异常率为91.3%(42/46),QST诊断 糖尿病周围神经病40例(86.9%),两者差异有显著性(P<0.05)。结论　QST较NCV对糖尿病周围神经病 变的诊断敏感性高;糖尿病患者温度觉异常率显著高于振动觉和NCV;提示其小神经纤维受损比大神经纤维 受损更常见。     

Follow-up of advanced diabetic neuropathy

Background The course of advanced diabetic neuropathy (DN) is largely unknown. Aim To find variables allowing the follow–up of late stages of DN. Methods Thirty diabetic patients with DN were observed. Patients were examined at intervals of 6 months over a period of 2 years. The compound muscle action potentials (CMAPs) were recorded in extensor digitorum brevis (EDB) and flexor hallucis brevis (FHB) muscles. Clinical severity of DN, nerve conduction studies (NCS), quantitative sensory testing (QST) and heart rate variability (HRV) were evaluated. The data were compared with age– and sex–matched controls. Results All measures were sensitive to the detection of DN. Significant deterioration during follow–up was exclusively found in CMAP analysis of the EDB (p < 0.05) and FHB muscles (p < 0.03). NCS, QST and HRV remained unchanged within the 2 years of observation. Coincidental changes might occur, if only two time points are chosen for followup. Conclusion Our results indicate that ongoing axonopathy predominates in advanced DN. Repeated testing helps to minimize the impact of coincidental or chance changes in DN follow–up studies.     

Acupuncture treatment improves nerve conduction in peripheral neuropathy

The etiology of peripheral neuropathy (PN) often remains elusive resulting in a lack of objective therapeutic strategies. We conducted a pilot study to evaluate the therapeutic effect of acupuncture on PN as measured by changes in nerve conduction and assessment of subjective symptoms. One hundred and ninety-two consecutive patients with PN as diagnosed by nerve conduction studies (NCS) were evaluated over a period of 1 year. Of 47 patients who met the criteria for PN of undefined etiology, 21 patients received acupuncture therapy according to classical Chinese Medicine as defined by the Heidelberg Model, while 26 patients received the best medical care but no specific treatment for PN. Sixteen patients (76%) in the acupuncture group improved symptomatically and objectively as measured by NCS, while only four patients in the control group (15%) did so. Three patients in the acupuncture group (14%) showed no change and two patients an aggravation (10%), whereas in the control group seven showed no change (27%) and 15 an aggravation (58%). Importantly, subjective improvement was fully correlated with improvement in NCS in both groups. The data suggest that there is a positive effect of acupuncture on PN of undefined etiology as measured by objective parameters.     

糖尿病性周围神经病患者受累神经的分布特点

目的 探讨糖尿病件周围神经病(DPN)患者受累神经的分布特点.方法 对900例2型糖尿病并发DPN患者进行感觉及运动神经传导速度检测,对受累神经的分布进行分析.结果 本组感觉神经异常率为89.3%;包括65.2%(587例)的正中神经、38.9%(350例)的尺神经、89.3%(804例)的腓浅神经、60.4%(544例)的腓肠神经及29.6%(64例)的胫后神经异常.运动神经异常率为34.5%;包括32.1%(289例)的正中神经、28.7%(258例)的腓总神经、22.7%(49例)的胫神经异常.感觉神经异常率明显高于运动神经异常率(P<0.01);下肢感觉神经异常率明显高于上肢(P<0.01).结论 DPN患者受累的感觉神经以腓浅神经、正中神经、腓肠神经最普遍,受累的运动神经以正中神经、腓总神经为多见.     

Prolonged ischemic conduction failure after reperfusion in diabetic nerve

Diabetic nerve exhibits morphological vulnerability to ischemia and reperfusion, in contrast to its physiological resistance to ischemic conduction failure (RICF). To examine the sequence of ischemic conduction failure after reperfusion in diabetic nerve, we measured sciatic-tibial nerve conduction before and during 30-180 min of ischemia and after reperfusion for up to 1 week in streptozocin (STZ)-induced diabetic rats. RICF in diabetic rats was confirmed during ischemia. After reperfusion, control nerves showed an immediate recovery in amplitude of compound muscle action potential (CMAP) following ischemia for 120 min or less, and delayed recovery after 150 min of ischemia. In contrast, recovery in diabetic nerves was delayed even after 1 h of ischemia. Ischemia for 75 min in diabetic nerve resulted in either delayed or no recovery of the CMAP upon reperfusion. Following ischemia for 90 or 120 min, axonal degeneration was observed in diabetic nerve. Thus, severe ischemia for 60 or 75 min causes prolonged ischemic conduction failure in diabetic nerve, compared with 150 min in control nerve. In conclusion, diabetic nerve shows delayed recovery of ischemic conduction failure after brief ischemia, compared to controls, suggesting that patients with diabetic neuropathy have a worse prognosis when faced with nerve ischemia.     

Assessment of diabetic neuropathy: Definition of normal and discrimination of abnormal nerve function

One hundred one normal subjects and 46 patients were investigated. Various objective and subjective tests for polyneuropathies were compared. Motor and sensory nerve conduction velocities are the most sensitive tests. In normals, age hardly influenced nerve conduction velocities. This is believed to be a result of the strict exclusion criteria. Diagnostic sensitivity is also high with the vibration fork test and with vibratometry at the big toe. Results with the method of limits are as reliable and sensitive as more cumbersome techniques, such as the titration method and the forced choice method. Thermal thresholds and cardiovascular tests are less sensitive. The most correct overall classification is attained with a combination of tests reflecting the function of different nerve fiber classes in the peripheral and autonomic nervous systems.