Diagnostic yield by testing small fiber function in patients examined for polyneuropathy

We assessed the diagnostic yield of adding quantitative sensory testing to the standard work-up for polyneuropathy in unselected patients. All patients aged 18 to 70 years referred to our department for electrodiagnosis with a tentative diagnosis of polyneuropathy and symptoms complying with predefined criteria were included in the study. We performed near nerve conduction studies in 4 nerves and determined heat and cold detection thresholds on hand and foot with a Thermotest (Somedic AB, Sweden). In order to uncover CNS diseases, somatosensory-evoked potentials were recorded in patients with abnormal quantitative sensory testing and normal nerve conduction studies. A total of 198 patients completed the study and 149 were considered to have polyneuropathy. Twenty-five patients remained undiagnosed and in 24 patients, other diseases were responsible for the symptoms. Of the patients with either polyneuropathy or no other diagnosis, 76% (n = 174) had abnormal nerve conduction. Abnormal cold sensation, heat sensation or abnormality in at least 1 of these and normal nerve conduction were found in 14, 12 and 17 patients. Of the 174 patients, 86% (95% CI 80-90%) had an abnormality in at least 1 of the tests (i.e. abnormal nerve conduction and/or abnormal quantitative testing of temperature sensation). In conclusion, quantitative testing of temperature sensation improves the diagnostic yield in patients examined for chronic polyneuropathy.     

定量感觉检查及神经传导速度测定对多发性神经病的诊断价值

目的探讨定量感觉检查(QST)及其联合神经传导速度(NCV)测定对多发性神经病的诊断价值。方法对60例多发性神经病患者进行QST以及感觉神经传导速度(SCV)、运动神经传导速度(MCV)检测,并比较各项检查的异常率。结果 QST的异常率(83.3%)显著高于SCV和MCV(50.0%,26.7%)(均P<0.05);SCV的异常率显著高于MCV(P<0.05)。QST联合SCV的异常率为95.0%,显著高于MCV的异常率(P<0.05)。结论 QST对多发性神经病的检出率较高,QST联合SCV对多发性神经病具有很高的诊断价值。     

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.     

Idiopathic polyneuropathy and impaired glucose metabolism in a Norwegian patient series

Background and purpose:  North American studies have indicated a high prevalence of impaired glucose tolerance (IGT) in patients with sensory polyneuropathy. We searched for the occurrence of IGT in a Norwegian patient material with polyneuropathy.
Methods:  Seventy patients with symptoms and signs of sensory polyneuropathy were included. Cases with known causes of neuropathy were excluded. All patients underwent a 2 h oral glucose tolerance test (OGTT). Nerve conduction studies (NCS), quantitative sensory testing (QST) and skin biopsy with assessment of intra-epidermal nerve fibre (IENF) density were performed.
Results:  Sixteen patients (23%) had impaired glucose metabolism (IGM): 2 (3%) were found to have diabetes, 9 (13%) had IGT, 3 (4%) had impaired fasting glucose (IFG) and 2 (3%) both IFG and IGT. About 62% of the patients with IGM and polyneuropathy and 50% of those with chronic idiopathic axonal polyneuropathy (CIAP) had abnormalities on NCS. Reduction of IENF occurred in 37% of the patients with IGM and 43% of those with CIAP.
Conclusions:  Patients with polyneuropathy and IGM had essentially the same degree of involvement of small and large nerve fibres as patients with CIAP. IGT seems less frequent in Norwegian patients with polyneuropathy than reported in North American populations.     

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.     

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.     

Motor nerve impairment in diabetic patients with symmetrical distal sensory polyneuropathy: A single nerve fiber conduction velocity study

Introduction: In this study we investigated the clinical utility of single fiber conduction velocity (SF‐CV) testing in the evaluation of motor nerve function in diabetic patients with signs and symptoms of symmetrical distal sensory polyneuropathy (DSP). SF‐CV findings were compared with conventional nerve conduction studies (NCS). Methods: Twenty‐eight consecutive type 2 diabetic patients with clinically diagnosed DSP were studied. Results: SF‐CV testing of the tibial nerve was abnormal in 16 (57.1%) patients. Twelve patients with normal conventional motor NCS had abnormal findings by tibial SF‐CV. SF‐CV testing of the tibial nerve was significantly superior to all other motor NCS. Conclusions: SF‐CV testing of the tibial nerve often demonstrates motor nerve impairment in diabetic patients with sensory DSP when conventional NCS are normal. Muscle Nerve 49 : 84–89, 2014     

Quantitative sensory testing of cold and vibration perception during compression of median nerve at the wrist

We conducted a sequential study of quantitative sensory testing (QST) during compression-induced conduction block of the median nerve to determine relative vulnerability of the small and large myelinated nerve fibers. We tested cold (CPT) and vibratory perception thresholds (VPT) of the third digit in 15 healthy subjects during constant, localized compression for 30 min of the median nerve at the wrist. The orthodromic sensory nerve action potentials (SNAPs) recorded at wrist and elbow served to monitor the degree of associated conduction block. After the onset of nerve compression, it took 16 min for CPT to show the first change; VPT remained normal for 26 min. CPT recovered 2 min later than VPT after release of compression. The SNAP amplitude at the wrist diminished immediately at the start of compression and declined progressively, whereas the response at the elbow remained the same initially, showing no latency change for 20 min. A nearly identical time course of SNAP changes in the two experiments justified the comparison of separately tested CPT and VPT as a measure of modality-specific vulnerability. Contrary to the common belief, a focal compression sufficient to produce rapidly reversible conduction abnormalities affects the slow-conducting small myelinated fibers mediating cold perception before the fast-conducting large myelinated fibers transmitting vibration perception. The data document the order of modality-specific vulnerability of sensory nerve fibers to mild compression. The finding suggests that testing CPT, rather than VPT, provides a better QST to delineate rapidly reversible symptoms induced by compression.     

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。     

吉兰-巴雷综合征和多发性神经病患者的温度觉及震动觉定量测定

目的了解定量感觉检查(QST)评价吉兰-巴雷综合征(GBS)及多发性神经病(PNP)患者感觉功能的作用。方法用温度觉分析仪(TSA-2001)及震动觉分析仪(VSA-6003)、以Limits法测定GBS、PNP及正常人左侧肢体四个部位的温度觉阈值(TT)及震动觉阈值(VT),GBS及PNP患者同时测了感觉传导速度(SCV)。结果GBS及PNP患者四肢远端存在冷、温觉阈值、震动觉阈值增大;QST比临床检查及SCV更敏感。GBS患者VT与SCV有显著相关性。PNP患者各部位的TT、VT与SCV无显著性相关。2例尿毒症性多发性神经病患者有矛盾性热感觉。结论QST对于周围神经感觉功能的评价是一敏感而可靠的方法,有助于周围神经病的诊断。     

定量感觉及神经传导检测在糖尿病患者中的应用比较

目的:分析定量感觉检查(QST)及神经传导检测(NCS)在糖尿病患者中的应用价值.方法:用QST对100例2型糖尿病(T2DM)组和50例正常对照组分别进行四肢的冷觉(CS)、温觉(WS)、冷痛觉(CP)、热痛觉(HP)的感觉阈值测定并进行比较分析;并对T2DM患者进行上肢的正中神经、尺神经,下肢的胫神经、腓神经运动和感觉支的NCS、复合肌肉动作电位(CMAP)、感觉神经动作电位(SNAP)以及运动末梢潜伏期(DML)进行测定并分析.T2DM患者分为有症状组和无症状组,分别对QST及NCS的异常率进行分析并比较.结果:T2DM组QST和NCS结果与正常对照组比较差异有显著意义(P＜0.01); QST与NCS异常率比较差异有显著意义(P＜0.01),QST的异常率均显著大于NCS;提示糖尿病周围神经病(DPN)患者中周围神经小纤维受损比大纤维更明显,T2DM患者有症状组和无症状组各值比较差异均有显著意义(P＜0.01).结论:QST对DPN的早期诊断提供可靠依据,QST对DPN的诊断敏感性高,但特异性低,需与NCS结合对糖尿病周围神经状况进行评价更为完善.QST和NCS不能相互替代,全面了解DPN病情需QST和NCS结合,并密切结合临床.     

Evaluation of carpal tunnel syndrome in patients with polyneuropathy

The difference between the median nerve latency to the second lumbrical muscle and the ulnar nerve latency to the second interosseous muscle (L-I DIFF) was tested in a prospective study to discriminate whether prolonged distal motor latency of the median nerve in patients with polyneuropathy (PNP) reflects an additional carpal tunnel syndrome (CTS). We investigated 92 patients (107 hands) with CTS, 30 patients (34 hands) with PNP, 22 patients (27 hands) with CTS and coexisting PNP (PNP+CTS), and 77 controls (87 hands). L-I DIFF was significantly prolonged in both the CTS and PNP+CTS patients as compared to PNP patients and controls. It proved to be the most specific test to differentiate between diffuse (PNP) and focal (entrapment) nerve disorder. © 1997 John Wiley & Sons, Inc. Muscle Nerve, 20, 153–157, 1997.     

Electrophysiological sensory demyelination in typical chronic inflammatory demyelinating polyneuropathy

Background: The presence of electrophysiological demyelination of sensory nerves is not routinely assessed in the evaluation of suspected chronic inflammatory demyelinating polyneuropathy (CIDP). Whether this can be useful is unknown. Methods: We compared, using surface recording techniques, in 19 patients with typical CIDP and 26 controls with distal large fibre sensory axonal neuropathy, the forearm median sensory conductions, sensory nerve action potential (SNAP) amplitudes and durations and sensory nerve conduction velocities (SNCVs) of median, radial and sural nerves. Results: Median nerve sensory conduction block (SCB) across the forearm was greater in CIDP patients than in controls (P = 0.005). SNAP durations were longer in CIDP patients for median (P = 0.001) and sural nerves (P = 0.004). Receiver operating characteristic (ROC) curves provided sensitive (>40%) and specific (>95%) cut‐offs for median nerve SCB as well as median and sural SNAP durations. SNCVs were significantly slower for median and sural nerves in CIDP patients, but ROC curves did not demonstrate cut‐offs with useful sensitivities/specificities. Median SCB or prolonged median SNAP duration or prolonged sural SNAP duration offered a sensitivity of 73.7% for CIDP and specificity of 96.2%. Used as additional parameters, they improved diagnostic sensitivity of the American Academy of Neurology (AAN) criteria for CIDP of 1991, from 42.1% to 78.9% in this population, with preserved specificity of 100%. Discussion: Sensory electrophysiological demyelination is present and may be diagnostically useful in typical CIDP. SCB detection and SNAP duration prolongation appear to represent more useful markers of demyelination than SNCV reduction.     

Is heat hypoalgesia a useful parameter in quantitative thermal testing of alcoholic polyneuropathy?

Detection of thermal hypoaesthesia, hyperalgesia, and paradoxical sensation significantly contribute to the diagnosis of polyneuropathy (PNP). There is controversy about the clinical usefulness of detected heat hypoalgesia. In 50 chronic alcoholic patients we compared the prevalence and diagnostic value of heat hypoalgesia (HPT) to that of cold (CT) and warm (WT) hypoaesthesia using a “Marstock” thermotest. Clinical examination revealed PNP in 56%, cold hypoaesthesia was present in 62%, warm hypoaesthesia in 24%, paradoxical thermal sensation in 10%, cold and heat hyperalgesia in 12%, and heat hpypoalgesia in 22%. Only 1 patient (2%) presented with heat hypoalgesia but normal warm and cold thresholds; he reported paradoxical thermal sensation and had PNP. One patient suffered first degree burn injury from heat pain examination. Heat hypoalgesia contributed least to the diagnosis of polyneuropathy (HPT versus CT: P < 0.001). In patients with sensory loss, testing heat hypoalgesia bears some risk of burn injury. In contrast to thermal hypoaesthesia and hyperalgesia, it does not significantly enrich the diagnostic workup of alcoholic polyneuropathies. © 1994 John Wiley & Sons, Inc.     

The value of skin biopsy with recording of intraepidermal nerve fiber density and quantitative sensory testing in the assessment of small fiber involvement in patients with different causes of polyneuropathy

The primary aim of our study was to demonstrate how the diagnostic characteristics of skin biopsy used to evaluate small fiber involvement in patients with different causes of polyneuropathy are intrinsically related to the method used to establish the reference values (cut-off values). We also investigated intraepidermal nerve fiber (IENF) density and abnormalities in quantitative sensory testing (QST) in patients with different causes of polyneuropathy and signs of small fiber involvement. A total of 210 patients with symptoms and signs of polyneuropathy were entered into the study. All patients underwent neurological examination, nerve conduction studies, QST on the thigh and distal part of the calf with detection of warm and cold perception thresholds, and skin biopsy with assessment of IENF density. Cut-off values for IENF density were established from our reference material using Z-scores (calculated from multiple regression analysis), fifth percentile, and receiver operating characteristic (ROC) analysis. Of the patients participating in the study, 65 had an established diagnosis of diabetes mellitus, 70 were classified with idiopathic polyneuropathy, and 75 had other possible causes of polyneuropathy. Forty-five patients met the criteria for small fiber polyneuropathy (SFN), and the remaining 165 had also involvement of large nerve fibers. Of the total patient cohort, 84 (40%) had reduced IENF density based on the Z-score, and 106 patients (50%) had at least one abnormality based on QST. In the SFN group, skin biopsy showed a sensitivity of 31% and a specificity of 98% when reference values were presented with Z-scores. When the fifth percentile was used as the cut-off value (6.7 fibers/mm), sensitivity was 35% and specificity 95%. Applying the ROC analysis with a chosen sensitivity of 78% and specificity of 64%, we had a cut-off point of 10.3 fibers/mm. We conclude that skin biopsy with assessment of IENF is a useful method for investigating patients with SFN. The diagnostic value of the test, however, depends upon on the approach used to estimate the reference values. An erratum to this article can be found at     

Sensory testing versus nerve conduction velocity in diabetic polyneuropathy.

We sought to evaluate the utility of quantitative sensory testing (QST) and nerve conduction velocity (NCV) studies as measures of distal symmetric polyneuropathy (DSP). We studied 36 diabetic patients divided into four clinical categories of increasing severity. QST included thermal testing and vibration thresholds. NCV studies included median, peroneal, and sural nerves. Results of QST and NCV were compared among clinical groups using survival methodology. The log-rank statistic showed significant differences among the groups; the direction of the differences were consonant with clinical severity. For each diabetic patient, the result of each measurement was classified as normal or abnormal; more diabetic patients had abnormal NCV than either vibration tests or thermal tests. In conclusion, findings of QST and NCV are in keeping with clinical categorization of patients, QST and NCV are complementary tests, and the sural sensory study is the best single predictor of DSP.     

Patterns of sensory nerve conduction abnormalities in demyelinating and axonal peripheral nerve disorders

The pattern of an abnormal median-normal sural (AMNS) sensory response is associated with acute and chronic inflammatory demyelinating polyradiculoneuropathy (AIDP and CIDP) and considered unusual in other types of neuropathy, although specificity and sensitivity of this pattern have not been evaluated. We compared sensory responses (patterns and absolute values) in patients with AIDP, CIDP, diabetic polyneuropathy (DP), and motor neuron disease (MND). Using strict criteria, the AMNS pattern occurred more frequently in recent onset AIDP (39%) compared with CIDP (28%), DP (14%–23%), or MND (22%) patients. This pattern was found in 3% of control subjects. The extreme pattern of an absent median-present sural response occurred only in AIDP and CIDP patients and in no other groups. Abnormalities of both nerves were more common in long-standing polyneuropathies such as CIDP and DP compared with AIDP or MND. Median nerve amplitudes were reduced significantly in AIDP, CIDP, and DP patients compared with MND patients, whereas sural nerve amplitudes were significantly reduced only in DP and CIDP patients. These findings may reflect early distal nerve involvement particularly in AIDP patients which is highlighted by differences in median and sural nerve recording electrode placement. We conclude that, in the appropriate clinical setting, the AMNS pattern, an absent median-present sural response pattern, or a reduced median amplitude compared with the sural amplitude supports a diagnosis of a primary demyelinating polyneuropathy. © 1993 John Wiley & Sons, Inc.     

Nerve conduction and biopsy correlation in over 100 consecutive patients with suspected polyneuropathy

Neuropathy was classified physiologically and histologically as normal, axonal, demyelinative, or indeterminate using specific motor nerve conduction (NC) and sural sensory nerve biopsy (NB) criteria. Physiological and histological diagnoses were concordant in 63%, and minimally discordant in 14% of patients. The most important discordant patients were 6 with demyelinative neuropathy, 4 by NC, of which 2 were pure motor syndromes, and 2 by NB, both predominantly sensory syndromes. In the 55 patients with predominant axonal degeneration on biopsy, the extent of NC slowing was determined. As compound motor and sensory nerve action potential (CMAP and SNAP) amplitude declined, distal motor latency increased, whereas motor and sensory conduction velocity (CV) did not. Minimum F response latency increased as motor CV decreased, more in lower than upper extremity nerves. We conclude that: (1) except for sensory neuropathy, routine motor NC studies generally suffice in identifying demyelinative neuropathy; (2) NC slowing in axonal neuropathy is usually slight but may result in significantly prolonged distal motor latencies when CMAP amplitude is very low, and prolonged F wave latency when motor CV is slightly low; and (3) The physiologic criteria employed in this study rarely misclassifies neuropathy as demyelinative in patients with predominant axon loss on biopsy. © 1994 John Wiley & Sons, Inc.