Cardiovascular reflex evaluation for detecting autonomic neuropathy in chronic dialysis patients

3 cardiovascular reflexes were tested in 25 patients on regular haemodialysis: measurement of the beat-to-beat variation in heart rate in the supine position and during deep breathing, measurement of heart rate response to change in posture (30:15 ratio). 8 patients (32%) had abnormal results in at least two of the tests, 3 patients (12%) had abnormal results in all 3 tests. Beat-to-beat variation was found to be the most sensitive test, the heart rate difference during deep breathing showing a direct correlation to the nerve conduction velocity of the peroneal nerve. Hence, a common cause can be postulated in the pathogenesis of the autonomic lesions and the sensorimotor polyneuropathy in the patients under investigation. Furthermore, the group with the most severe radiological calcification due to M?nckeberg's medial sclerosis had a significantly lower mean heart rate difference during deep breathing than the group with no radiological calcification. A similar correlation between autonomic neuropathy and M?nckeberg's medial sclerosis has recently been described in diabetic patients.     

Detection of autonomic sympathetic dysfunction in diabetic patients. A study using laser Doppler imaging

OBJECTIVE: To study signs of the disturbed reflex autonomic sympathetic nerve function in type 1 and type 2 diabetic patients. RESEARCH DESIGN AND METHODS: Measurements were made on 15 type 1 (duration 13-32 years) and on 50 recently diagnosed type 2 diabetic patients (duration 3-4 years). The vasoconstrictor responses in the distal phalanx of the middle finger (locally heated to 40 degrees C) to the cooling of the contralateral arm were measured using Laser Doppler Imaging (LDI). A vasoconstriction index (VAC) was calculated taking age into account and was compared with reference values obtained in 80 control subjects. The diabetic patients were also studied with deep-breathing tests (i.e., the heart-rate variation expressed as the expiration-to-inspiration [E/I] ratio, a test of parasympathetic nerve function). RESULTS: The vasoconstrictor responses to indirect cooling (VAC) were significantly reduced in the fingers of the diabetic patients, both type 2 (0.77 +/- 0.02 V; P < 0.01) and type 1 (0.83 +/- 0.04 V; P < 0.001), compared with the healthy control subjects (0.65 +/- 0.01); the age-corrected VAC (VACz) was slightly more impaired in type 1 than in type 2 diabetic patients. The frequency of an abnormal VACz corresponded well to the frequency of an abnormal E/I ratio in type 1 diabetic patients (approximately 50%), whereas the frequency of an abnormal VACz was significantly higher than an abnormal E/I ratio among type 2 diabetic patients (11/50 vs. 4/50; P < 0.05). CONCLUSIONS: Both type 1 and type 2 diabetic patients have impaired cutaneous blood flow regulation. The VAC index seems to be a promising tool for detection of subclinical changes in autonomic sympathetic function.     

Enhanced pain and autonomic responses to ambiguous visual stimuli in chronic Complex Regional Pain Syndrome (CRPS) type I

Cortical reorganisation of sensory, motor and autonomic systems can lead to dysfunctional central integrative control. This may contribute to signs and symptoms of Complex Regional Pain Syndrome (CRPS), including pain. It has been hypothesised that central neuroplastic changes may cause afferent sensory feedback conflicts and produce pain. We investigated autonomic responses produced by ambiguous visual stimuli (AVS) in CRPS, and their relationship to pain. Thirty CRPS patients with upper limb involvement and 30 age and sex matched healthy controls had sympathetic autonomic function assessed using laser Doppler flowmetry of the finger pulp at baseline and while viewing a control figure or AVS. Compared to controls, there were diminished vasoconstrictor responses and a significant difference in the ratio of response between affected and unaffected limbs (symmetry ratio) to a deep breath and viewing AVS. While viewing visual stimuli, 33.5% of patients had asymmetric vasomotor responses and all healthy controls had a homologous symmetric pattern of response. Nineteen (61%) CRPS patients had enhanced pain within seconds of viewing the AVS. All the asymmetric vasomotor responses were in this group, and were not predictable from baseline autonomic function. Ten patients had accompanying dystonic reactions in their affected limb: 50% were in the asymmetric sub‐group. In conclusion, there is a group of CRPS patients that demonstrate abnormal pain networks interacting with central somatomotor and autonomic integrational pathways.     

Autoantibodies to autonomic nerves associated with cardiac and peripheral autonomic neuropathy

OBJECTIVE: This study examines whether autonomic nerve autoantibodies (ANabs) are associated with development of autonomic neuropathy using a prospective study design. RESEARCH DESIGN AND METHODS: A group of type 1 diabetic patients were followed prospectively with regard to autonomic nerve function on four occasions. At the third examination, 41 patients were tested for ANabs (complement-fixing autoantibodies to the sympathetic ganglion, vagus nerve, and adrenal medulla), and the results were related to cardiac autonomic nerve function (heart rate variation during deep breathing [expiration/inspiration ratio] and heart-rate reaction to tilt [acceleration and brake index]) and to peripheral sympathetic nerve function (vasoconstriction after indirect cooling [vasoconstriction index]). RESULTS: ANabs were detected in 23 of 41 (56%) patients at the third examination. Compared with patients without ANabs (ANabs-), patients with ANabs (ANabs+) showed significantly higher frequencies of at least one abnormal cardiac autonomic nerve function test at the third examination (17 of 23 [74%] vs. 7 of 18 [39%]; P = 0.03) and fourth examination (15 of 21 [71%] vs. 4 of 16 [25%]; P < 0.01). In contrast, there was no similar difference at the first or second examination. The relative risk for ANabs(+) patients to develop cardiac autonomic neuropathy at follow-up was 7.5 (95% CI 1.72-32.80). The vasoconstriction index was more abnormal in ANabs+ than in ANabs- patients at the fourth examination (median 1.40 [interquartile range 1.58] vs. 0.35 [2.05]; P = 0.01). CONCLUSIONS: ANabs were associated with future development of cardiac and peripheral autonomic neuropathy in diabetic patients, implying an etiological relationship between nervous tissue autoimmunity and these diabetes complications.     

双PW多普勒超声观察电刺激腓神经对小腿 血液循环的影响

摘要 目的 应用双PW多普勒超声检查技术同步测量腘动、静脉血流动力学变化,探讨电刺激腓神经对小腿血液循环的影响。方法 健康志愿者20例（年龄20-40岁）。采用FirstKind公司geko T-1电刺激装置,应用日立公司HI VISION Ascendus图腾彩色多普勒超声诊断仪,利用双多普勒超声检查技术测量基础状态及电刺激腓神经不同时间段,腘动脉和腘静脉血流峰值速度及血流量变化。结果 电刺激腓神经后,腘静脉的峰值速度显著增加（P<0.05）,每搏量及单位时间流量在电刺激15min后达到高峰;腘动脉的峰值速度及血流量则增加不明显,但阻力指数及搏动指数显著升高（P<0.05）。结论 电刺激腓神经可以促进小腿血液循环,增加肢体远端动脉血管阻力,促进下肢静脉回流。     

The influence of ulnar nerve blockade on skin microvascular blood flow*

Abstract. Microvascular research is seriously hampered by the great temporal and spatial variability of the measured skin blood flow and variation in sympathetic vasomotor reflexes within and between persons. Therefore skin vasomotor reflexes were studied before and after ulnar nerve blockade within the same person, resulting in a temporal complete denervation of the fifth finger and partial denervation of the fourth finger. Skin temperature and laser Doppler flux (LDF) were registrated to measure predominantly arteriove-nous shuntflow. Measurements were performed on the palmar tip of the second and fifth finger in nine healthy volunteers, at baseline, and during a sympathetic reflex test (i.e. inspiratory gasp) and postural response test. Beat-to-beat digital blood pressure was recorded from the third and fourth finger by a Finapres device. Baseline capillary blood cell velocity (CBV) was measured at the nailfold of the second and the fifth finger. After ulnar blockade baseline skin temperature, LDF and CBV increased significantly, with respectively (mean±SE) 3.2±0.9d?C, 20.9 ±5.9 relative perfusion units and 0.79 ±0.40 mm^-1 s. The percentage LDF decrease of the fifth finger during inspiratory gasp was 48.2 ±5.3% before and 31 ±0.9% after blockade. The postural response test showed a decrease in LDF of the fifth finger with no significant difference before and after blockade, respectively 12.3± 14.7% and 8.0±2.7%, while no difference was found in the increase in digital blood pressure in the denervated fourth finger compared to both the same finger before blockade and to the third non-blocked finger. It is concluded that ulnar nerve blockade enables the study of sympathetic skin vasomotor reflexes by comparison of a denervated and a non-denervated vascular bed within the same person. After ulnar blockade arteriovenous shunt flow as well as nutritional capillary blood flow increased significantly. Postural vasoconstrictor response is not abolished by ulnar blockade, suggesting that local regulatory mechanisms are more important.     

Forearm vasoconstrictor response in uncomplicated type 1 diabetes mellitus

BACKGROUND: According to the 'haemodynamic hypothesis', increased tissue perfusion predisposes to microangiopathy in diabetic patients. We hypothesized that the typical haemodynamic changes underlying the increased tissue perfusion can be explained by a decreased sympathetic nerve activity caused by chronic hyperglycaemia. In this study we investigated sympathetic activity in patients with uncomplicated type 1 diabetes mellitus (DM). MATERIALS AND METHODS: In 15 DM patients (DM duration 6.3 +/- 3.8 year; HbA1c 7.9 +/- 1.3%) and 16 age- and sex-matched healthy volunteers (Control), sympathetic nervous system activity was measured at rest (baseline) and during sympathoneural stimulation (lower body negative pressure (LBNP)) by means of interstitial and plasma noradrenaline (NA) sampling and power spectral analysis. Muscle sympathetic nerve activity (MSNA) was measured before (baseline) and during a cold pressure test. Forearm blood flow was measured during forearm vascular alpha- and beta-adrenergic receptor blockade. RESULTS: At baseline, forearm vascular resistance (FVR), plasma NA concentrations, MSNA and heart rate variability were similar in both groups. LBNP-induced vasoconstriction was significantly attenuated in the DM group compared with the Control group (DeltaFVR: 12 +/- 4 vs. 19 +/- 3 arbitrary units, P < 0.05). The responses of plasma NA and heart rate variability did not differ. CONCLUSIONS: Baseline FVR and sympathetic nerve activity are normal in patients with uncomplicated type 1 diabetes. However, the forearm vasoconstrictor response to sympathetic stimulation is attenuated, which cannot be attributed to an impaired sympathetic responsiveness.     

尿毒症患者周围神经的电生理研究

目的研究尿毒症患者周围神经的电生理表现。方法选择尿毒症患者24 例及同期健康对照者19 例,采用常规表面电极对胫后神经、腓总神经、腓肠神经及皮肤交感反应进行检查,观察尿毒症患者周围神经的电生理表现。结果两组运动传导、感觉传导及交感皮肤反应潜伏期均有显著性差异(P<0.05)。电生理表现主要为F 波的潜伏期延长,传导速度减慢,潜伏期延长,感觉纤维受累重于运动纤维。结论尿毒症性周围神经病是尿毒症最常见的并发症之一,神经电生理的异常明显早于临床症状,周围神经的电生理检查对该病的诊断及评价具有重要意义。     

Uncoupling protein 2 promoter polymorphism -866G/A affects peripheral nerve dysfunction in Japanese type 2 diabetic patients

OBJECTIVE: To determine genetic predispositions for diabetic polyneuropathy, we investigated the relationship between the -866G/A polymorphism of uncoupling protein (UCP) 2 and neurological manifestations in 197 type 2 diabetic patients. RESEARCH DESIGN AND METHODS: We first examined whether UCP2 mRNA had been expressed in the dorsal root ganglion (DRG) in four Long-Evans Tokushima Otsuka rats using RT-PCR and electrophoresis. Genotyping of UCP2 promoter polymorphism -866G/A was then performed in 197 unrelated Japanese type 2 diabetic patients, who were subjected to nerve conduction, quantitative vibratory perception, head-up tilt, and heart rate variability tests, by PCR restriction fragment-length polymorphism. The relationships between UCP2 genotype and various nerve functions were analyzed by uni- and multivariable analysis. RESULTS: Expression of UCP2 mRNA was confirmed in rat DRG. Multiple regression analysis clarified the hypothesis that the G/A + A/A genotype was significantly related to decreased motor nerve conduction velocity and impaired blood pressure maintenance on the head-up tilt test. Multiple logistic regression analysis revealed that the G/A + A/A genotypes are a significant risk factor for sensory nerve conduction slowing and orthostatic hypotension. CONCLUSIONS: UCP2 promoter gene polymorphism -866 G/A was significantly associated with nerve conduction slowing and vasomotor sympathetic functions. These findings suggest that the higher UCP2 activity related to the A allele has an energy-depleting effect on peripheral nerve function in type 2 diabetic patients.     

右冠状动脉阻塞时交感神经对房室传导调节功能的实验研究

目的 研究右冠状动脉阻塞时交感神经对房室传导调节功能的影响. 方法 在去自主传出神经的动物上,结扎右冠状动脉造成急性下壁心肌梗死(AIMI)的动物模型,通过模板匹配的方法检测His束的A、H、V波,自动检测两心房波(AA)间期,心房波与His渡(AH)间期,并刺激双侧交感神经. 结果 正常动物刺激交感神经使得AH问期在未起搏与起搏时减少(14±5)%和(23±7)%;而心肌梗死时,刺激交感神经使AH间期在未起搏与起搏时减少(7±5)%和(12±2)%.后者只有前者减少幅度的50%和48%(P<0.05). 结论 在AIMI时,交感神经对心脏传导调节功能减弱,这种减弱可能参与AIMI伴房室传导阻滞发生的机制.     

Impaired diurnal cardiac autonomic function in subjects with type 2 diabetes

OBJECTIVE: To assess diurnal cardiac sympathetic and parasympathetic nerve functions in diabetic subjects with variable diabetic neuropathy. RESEARCH DESIGN AND METHODS: Frequency domain analysis of 24-h Holter ECG was done for 132 diabetic subjects (84 without any symptomatic neuropathy; 37 with only symptomatic peripheral neuropathy; 11 with symptomatic autonomic neuropathy) and 57 normal volunteers to calculate the low frequency (LF) component representing the beta-adrenoceptor function and the high frequency (HF) component representing the cardiac parasympathetic nerve function. RESULTS: Cardiac LF and HF components in diabetic subjects without peripheral neuropathy showed values comparable to those of normal volunteers and a similar circadian rhythm. Diabetic subjects with peripheral neuropathy or autonomic neuropathy showed significantly depressed LF and HF components and loss of the circadian rhythm of LF and HF components compared with diabetic subjects without neuropathy. Impairment of the LF component in the afternoon could be accounted for by the duration of diabetes and elevated HbA1c level. Impairment of the HF component at night could be accounted for by the duration of diabetes but not an elevated HbA1c level. CONCLUSIONS: These data indicated that diabetic subjects with peripheral neuropathy and diabetic subjects with symptomatic autonomic neuropathy, but not diabetic subjects without neuropathy, showed a marked decrease in cardiac sympathetic and parasympathetic nerve functions and loss of circadian rhythm.     

糖尿病周围神经病变与血液流变学相关性分析

目的 :分析糖尿病周围神经病变与血液流变学的相互关系。方法 :测定 114例糖尿病患者的正中神经、尺神经、腓总神经和腓浅神经的感觉神经传导速度 (SNCV)和运动神经传导速度 (MNCV)及其血液流变学指标。结果 :SNCV异常率为 5 9.4 % ,MNCV异常率为 5 3.6 % ,(P <0 .0 1)。随病程越长 ,NCV异常率逐渐升高。NCV异常组的全血黏度及红细胞聚集指数高于NCV正常组。结论 :改善血液流变学有助于延缓糖尿病性周围神经病变发生     

Muscle weakness and foot deformities in diabetes: relationship to neuropathy and foot ulceration in caucasian diabetic men

OBJECTIVE: To examine the relationships among muscle weakness, foot deformities, and peroneal and tibial nerve conduction velocity in diabetic and nondiabetic men. RESEARCH DESIGN AND METHODS: A neuropathic and foot evaluation was undertaken in 10 nondiabetic control subjects (group C) and in 36 consecutive diabetic patients attending Diabetes Centre clinics, including 10 diabetic control subjects (group D), 15 diabetic neuropathic patients (group DN), and 11 diabetic patients with a history of ulceration (group DU). Neuropathy was defined as a peroneal motor nerve conduction <40 m/s. Muscle weakness was assessed in seven intrinsic and seven extrinsic muscles of the foot using a semiquantitative score (max score per muscle = 3). Foot deformities were assessed using a foot deformity score (max score = 3). A higher score indicated increased muscle weakness or more severe foot deformities. Muscle weakness and foot deformities were assessed without prior knowledge of patient and neuropathy status. RESULTS: Peroneal and tibial nerve conduction velocity were associated with weakness in muscles innervated by, respectively, the peroneal and tibial nerve (r = -0.70 and r = -0.51, P < 0.01) and foot deformities (r = -0.60 and r = -0.59, P < 0.001). The DN and DU groups had more weakness in intrinsic and extrinsic muscles compared with the C and D groups. Muscles innervated by the tibial nerve had a greater proportional muscle weakness than those innervated by the peroneal nerve in the DN and DU groups. The DN and DU patients had more foot deformities (median food deformity score [interquartile range]) (3 [2-3] and 2 [2-3]) compared with D and C patients (0 [0-0.75] and 0 [0-0]). CONCLUSIONS: Important relationships have been shown between motor nerve conduction deficit and muscle weakness; however, it is still not clear whether abnormal nerve function, leading to a decrease in muscle strength, could be responsible for the development of foot deformities.     

The relation between sympathetically maintained pain,regional vasomotor disturbances and sympathetic nerve activity: a remaining enigma

In simultaneous bilateral nerve recordings, patients with Sympathetically Maintained Pain (SMP) affecting one limb show similar sympathetic traffic in nerves supplying the affected and unaffected limb, also when the painful limb shows a marked regional autonomic (vasomotor) dysfunction. These findings argue against the notion that SMP must be mediated by a reflex change in the pattern of sympathetic discharge. In general, they underline the fact that autonomic effector disturbances may give little information about underlying nerve traffic.     

TCD检测系统性红斑狼疮患者脑血流动力学变化

目的：了解系统性红斑疮患者脑血流动力学状况,方法;利用经颅我镨勒（ＴＣＤ）测定纤斑疮患者和健康对照组脑血管收缩峰速度（Ｖｓ）、舒张期血流速度（Ｖｄ）、平均血流速度（Ｖｍ）、收缩／舒张比值（Ｓ／Ｄ）、血管搏动指数（ＰＩ）、阻力指数ＲＩ）。结果：红斑狼疮患者无Ｖｓ、Ｖｍ是否升高,各脑血管Ｖｄ均较对照组显著增快（Ｐ〈０．０１）,ＰＩ、ＲＩ显著降低（Ｐ〈０．０１）,突出表现为低的ＴＣＤ频谱改变。结论：红斑     

彩色多普勒对人肝血管餐前、后血流动力学的研究

目的观测正常成人入肝血管(肝动脉、门静脉)餐前、后血流动力学改变,探讨其相互关系及其临床意义。方法应用彩色多普勒超声分别测量50例正常成人餐前、后入肝血管的血流参数,包括门静脉主干的直径(D),最大血流速度(Vmax),血流量(Q),肝右动脉的收缩期峰值速度(Vmax),舒张末期峰值速度(Vmin),时间平均速度(Vmean),阻力指数(RI),搏动指数(PI)等,探讨其相互关系。结果餐前肝右动脉和门静脉各主要血流参数分别为肝右动脉RI0.65±0.04,PI1.20±0.17,门静脉主干最高血流速度为(17.80±2.14)cm/s,血流量为(905.55±162.50)ml/min;餐后肝右动脉和门静脉各主要血流参数分别为肝右动脉RI0.73±0.04,PI1.74±0.51,门静脉主干最高血流速度为(22.40±3.25)cm/s,血流量为(1279.24±239.84)ml/min。结论餐前、后肝右动脉和门静脉各血流参数间存在显著差异(P＜0.05),肝动脉和门静脉血流量存在彼消此长的关系,以维持入肝血流的相对衡定。     

黄芪桂枝五物汤治疗糖尿病周围神经病变气虚血瘀证Meta分析

目的:系统评价黄芪桂枝五物汤治疗糖尿病周围神经病变(气虚血瘀证)安全性和有效性。方法:检索中国知网(CNKI)、中国生物医学文献数据库(CBM)、维普全文数据库(VIP)、万方医学网、PubMed,检索至2020年04月正式发表的黄芪桂枝五物汤治疗糖尿病周围神经病变的文献,按照纳入标准和排除标准,纳入文献,提取资料,采用RevMan 5.3进行Meta分析。结果:共纳入14篇文献,1062例患者,实验组532例,对照组530例。在临床疗效、正中神经(运动纤维)传导速度、正中神经(感觉纤维)传导速度、腓总神经(运动纤维)传导速度上,两组差异具有统计学意义,空腹血糖、餐后2h血糖无明显统计学差异。结论:在现有文献基础上,黄芪桂枝五物汤治疗糖尿病周围神经病变(气虚血瘀证)可提高临床疗效,提高正中神经(运动纤维)、正中神经(感觉纤维)、腓总神经(运动纤维)传导速度。     

糖尿病大鼠视网膜TNF-a表达与视网膜血流改变的实验研究

目的通过对糖尿病大鼠视网膜中央动、静脉血流以及肿瘤坏死因子-a（TNF-a）在其视网膜的表达进行连续6个月的测定，探讨分析两者的关系。方法采用右下腹腔内一次性注射Streptozotocin 60 mg／kg诱导Wistar大鼠糖尿病模型35只，分别于成模后1、2、3、4、5和6个月，行彩色多普勒血流检查、视网膜血管消化铺片、视网膜TNF-a的免疫组织化学检测。结果随糖尿病病程延长，TNF-a的阳性表达数目、着色程度及分布范围相应的增加，视网膜动脉血流速度减低，搏动指数、阻力指数增加，静脉流速增加，视网膜微血管狭窄闭塞。结论糖尿病大鼠视网膜血流状况的改变与TNF-a的阳性表达同时存在，TNF-a的阳性表达的强弱与视网膜血流状况不良成正比。     

Correlations among autonomic, sensory, and motor neural function tests in untreated non-insulin-dependent diabetic individuals

A well-defined group of untreated non-insulin-dependent (NIDD) subjects were evaluated to determine whether involvement of neural function measurements is generalized and symmetrical and to compare the autonomic, sensory, and motor neural measurements. After age adjustment, the sensory and motor neural function measurements were significantly slower in the diabetic group than in normal subjects (P less than 0.01). Similarly, the autonomic nervous system function measurements were also abnormal in the NIDD group (P less than 0.01). Further analysis revealed that each of the specific measurements--median motor nerve conduction velocity (NCV,P less than 0.005), peroneal motor NCV (P less than 0.005), median sensory NCV (P less than 0.005), dark-adapted pupil size after muscarinic blockade (P less than 0.02), pupillary latency time (P less than 0.02), and RR-variation after beta adrenergic blockade (P less than 0.001)--was significantly less by analysis of covariance after age adjustment in the NIDD group than in normal subjects. Thus, there was evidence of motor and sensory neural impairment in the upper and lower extremities as well as evidence of impairment of the reflex arcs involving the parasympathetic nerves to the heart and eye and the sympathetic nerves to the iris. Further analysis revealed that right and left NCV were correlated (P less than 0.01), as were the median motor and median sensory NCV (P less than 0.01), the median motor and peroneal motor NCV (P less than 0.001), and the peroneal motor and median sensory NCV (P less than 0.001). Thus, there was evidence of symmetrical upper and lower limb, as well as motor and sensory proportional involvement of large nerve fiber NCV in this group of NIDD subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Factor analysis. A methodology for data reduction in nerve conduction studies.

Analyzing multiple nerve conduction study parameters individually is statistically problematic. The goal of this study was to develop a useful factor analysis scheme for assessment of nerve conduction study abnormalities in diabetic neuropathy. Hypotheses were: (1) factor analysis produces a few physiologically meaningful factors, (2) there are associations between factors and markers of diabetic severity and (3) clinical impressions are related to factor scores. We studied 165 Japanese-American men: 52 nondiabetic, 66 diabetic and 47 with impaired glucose tolerance. One author (W.C.S.) obtained 28 nerve conduction study parameters in all subjects and factor analysis extracted five factors from these parameters. These factors were related to conduction velocities (factor 1), distal ulnar function (factor 2), sensory amplitudes (factor 3), distal median function (factor 4) and distal peroneal function (factor 5); together, they explain 57% of the variability in the total data. Diabetic factor scores were significantly (P less than 0.05) below that of the controls and correlations with fasting blood sugar were significant at the P less than or equal to 0.001 level. Use of this technique promises to permit sensible analysis of large amounts of data in clinical studies of diabetic and other types of polyneuropathy.