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1.
Introduction: We evaluated incorporation of the quantitative sudomotor axon reflex test (QSART) into the diagnostic criteria for small fiber neuropathy (SFN) as an addition to quantitative sensory testing (QST) and intraepidermal nerve fiber density (IENFD) testing. Methods: One hundred one patients with clinically suspected SFN underwent QSART, QST, and skin biopsy. The diagnostic yield of existing SFN criteria in these patients was compared with criteria incorporating QSART. The new combined diagnostic criteria were evaluated. Results: SFN was diagnosed in 38 of the 101 patients (38%) using current criteria. Addition of QSART existing SFN criteria resulted in an increased diagnostic yield to 67 patients (66%). Applying new SFN criteria requiring abnormality in at least 2 assessments among QSART, QST, and IENFD resulted in a diagnosis of SFN in 57 patients (56%). Conclusion: Assessment of both somatic and peripheral autonomic small nerve fibers enhances diagnostic criteria for SFN. Muscle Nerve 48 : 883–888, 2013  相似文献   

2.
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  相似文献   

3.
Predictors of response to neuropathic pain treatment in patients with painful distal sensory neuropathies are lacking. The 5% lidocaine patch is believed to exert its effects on neuropathic pain via a local stabilizing effect on cutaneous sensory afferents. As such, it provides a model to assess whether the status of epidermal innervation as determined by skin biopsy or quantitative sensory testing (QST) of small- and large-diameter sensory afferents might serve as predictors of response to topical, locally active treatment. In this study we assessed associations between epidermal nerve fiber (ENF) densities, sensory nerve conduction studies (NCS), QST, and response to a 5% lidocaine patch in patients with painful distal sensory neuropathies. We observed no association between distal leg epidermal and subepidermal innervation and response to the lidocaine patch. Several patients with complete loss of distal leg ENF showed a response to the lidocaine patch. Similarly we observed no consistent association between treatment response and QST for vibration, cooling, warm, heat-pain, and cold-pain thresholds, or distal sensory NCS. Thus, distal-leg skin biopsy, QST, and sensory NCS cannot be used to identify patients with painful polyneuropathy likely to respond to a lidocaine patch in clinical practice. Further studies are required to clarify precisely the mechanism and site of action of the lidocaine patch in patients with peripheral neuropathic pain.  相似文献   

4.
Intraepidermal nerve fiber density as a marker of early diabetic neuropathy   总被引:5,自引:0,他引:5  
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.  相似文献   

5.
Introduction: We evaluated diagnostic value of sensory tests during recovery from iatrogenic sensory neuropathy using intraoperatively verified nerve injury with subjective symptoms as gold standard. Methods: Inferior alveolar nerves were monitored neurophysiologically throughout mandibular osteotomy in 19 patients. Sensory disturbance was registered and sensation tested using clinical and quantitative sensory (QST) and neurophysiologic tests postoperatively at 1, 3, 6, and 12 months. Sensitivity, specificity, and predictive values were calculated for all tests. Results: The sensitivity of clinical tests was at best 37%, with 100% specificity, but they lost diagnostic value at chronic stages. Best diagnostic accuracy (highest combination of sensitivity and specificity) at different time points was achieved by combining neurophysiologic and thermal QST or tactile and thermal QST. The single most accurate test was sensory neurography. Conclusions: Neurography or combinations of neurophysiologic and quantitative tests enables most reliable early and late diagnosis. Clinical sensory examination is inadequate for accurate diagnosis. Muscle Nerve 59 :342–347, 2019  相似文献   

6.
Fabry's disease is commonly associated with a painful, debilitating neuropathy. Characterization of the physiological abnormalities is an important step in evaluating response to specific therapies. Twenty-two patients with Fabry's disease, and with relatively preserved renal function, underwent conventional and near-nerve conduction studies, electromyography, sympathetic skin responses, and quantitative sensory testing (QST). Nerve conduction studies were mostly normal except for an increased frequency of median nerve entrapment at the wrist in 6 (27%) patients. Sympathetic skin responses were preserved in 19 of 20 (95%) of the patients. The QST showed increased or immeasurable cold and warm detection thresholds in patients, significantly different from controls (n = 28) in the hand (P < 0.001, P = 0.04, respectively) and foot (P < 0.001 for both). Cold thresholds were more often abnormal than were warm thresholds. Vibration thresholds were normal in the feet and, in some patients, elevated in the hand only, probably due to frequent median nerve entrapment at the wrist. Our findings suggest that the neuropathy of Fabry's disease is characterized by an increased prevalence of median nerve entrapment at the wrist and by thermal afferent fiber dysfunction in a length-dependent fashion, with greater impairment of cold than warm sensation.  相似文献   

7.
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.  相似文献   

8.
Introduction: Meralgia paresthetica is a focal neuropathy caused by compression of the lateral femoral cutaneous nerve (LFCN). The disease can be difficult to assess by neurophysiological or imaging studies. Methods: We studied 5 patients who presented to our neuromuscular clinic from April 2012 to December 2014 with a clinical suspicion of meralgia paresthetica and had skin biopsies with intraepidermal nerve fiber density (IENFD) evaluation. Results: The mean age at onset was 37.2 (range 21–59) years. There were 4 women and 1 man. Two were obese, 2 wore tight jeans, and 1 had mild diabetes mellitus. IENFD was reduced in the symptomatic proximal thigh in all 5 patients and was also reduced in the asymptomatic thigh in 2 patients. It was normal in the distal leg in 4 patients. Conclusion: Meralgia paresthetica is associated with loss of small intraepidermal nerve fibers. Skin biopsy with IENFD evaluation may be a useful diagnostic tool for this disease. Muscle Nerve 53 : 641–643, 2016  相似文献   

9.
《Clinical neurophysiology》2008,119(6):1365-1372
ObjectiveTo examine the neurologic and neurophysiologic findings and neurologic symptoms in 12 women with Fabry disease and to study the relationship between the subjective symptoms and the findings on the various tests done.MethodsNeurography, vibratory and thermal quantitative sensory testing (QST), skin biopsy for measuring intraepidermal nerve fiber density (IENFD). Heart rate variability (HRV) and sympathetic skin response (SSR) tests for detecting autonomic dysfunction, pain-, depression- and somatic symptom questionnaires and clinical examination.ResultsOnly two women had no persistent symptoms or signs of polyneuropathy, 10 had symptoms of small fiber neuropathy. Neurological examination was normal in most patients. Five patients had decreased IENFD or thermal hypoesthesia in QST. In QST, Aδ-fiber function for innocuous cold was more often impaired than C-fiber function. Conventional nerve conduction studies were mostly normal. Carpal tunnel syndrome (CTS) incidence was increased, 25% had symptomatic CTS.ConclusionsHeterozygous women carrying the gene for Fabry disease have symptoms and findings of small-fiber polyneuropathy more often than has previously been considered. The prevalence of CTS is also increased.SignificanceWhile the clinical diagnosis of small-fiber neuropathy is difficult, the diagnostic yield can be increased using a combination of thermal QST and IENFD measurements.  相似文献   

10.
We investigated the associations of baseline epidermal nerve fiber (ENF) densities and morphology (percent ENF swellings) and quantitative sensory testing (QST) with clinically defined human immunodeficiency virus (HIV)-associated distal polyneuropathy (DSP) and whether these measures are predictive of development of symptomatic DSP over time. Fifty-seven HIV-infected subjects with and without DSP and 19 controls participated. Mean ENF densities were lower at the distal leg and proximal thigh in asymptomatic or symptomatic DSP than in controls. Mean ENF densities did not differ significantly among the HIV groups. Percent ENF swellings was higher in patients with symptomatic DSP than controls at the distal leg, and was also greater at the proximal thigh in patients with asymptomatic or symptomatic DSP than in controls. The percent ENF swellings at the distal leg correlated with the thresholds for both minimal (HP 0.5) and intermediate (HP 5.0) heat pain (HP) intensity. A higher percent ENF swellings in the distal leg [hazard ratio (HR) 1.16, 95% CI 1.02-1.31] and HP 0.5 thresholds (HR 1.03, 95% CI 1.01-1.05) were the only two measures associated with a shorter time to development of symptomatic DSP. Quantitation of ENF swellings and heat pain thresholds deserve further study as predictors of symptomatic neuropathy.  相似文献   

11.
We investigated the agreement between simple indirect immunofluorescence (IF) and bright‐field immunohistochemistry (BFI) on free‐floating sections for intraepidermal nerve fiber density (IENFD) quantification. Fifty‐five healthy subjects and 63 patients with probable small fiber neuropathy (SFN) underwent two adjacent skin biopsies at the distal leg processed by IF and BFI technique. Agreement between IENFD pairs obtained by each method was assessed by Bland–Altman testing. The area under the curve of the receiving operating characteristics (ROC) curves was used to compare the discrimination ability. The diagnostic judgment was based on sex and age‐adjusted normative values. IF and BFI showed good correlation (r = 0.81), with a ratio of about 2:1 and a mean difference of 5.5 ± 3.0 IENF per millimeter between paired measures, as demonstrated by linear regression and Bland–Altman test analyses. The square root transformation confirmed a Poisson distribution of the data and a fixed bias between IF and BFI measurements. The ROC curves analysis demonstrated a striking overlap between IF and BFI (0.83 and 0.82; p = 0.72). The diagnosis of SFN disagreed in only 6.7% of cases when the judgment was based on a difference of >1 IENF from 5% cut‐off value. IF and BFI showed comparable diagnostic efficiency when referred to appropriate normative reference values.  相似文献   

12.
We prospectively evaluated the effect of enzyme replacement therapy (ERT) on the intraepidermal nerve fiber density (IENFD) and thermal threshold in patients with Fabry disease, an X-linked disorder associated with a painful small-fiber neuropathy and decreased linear IENFD in a length-dependent pattern. Twenty-five hemizygous male patients with Fabry disease were enrolled in a 6-month, randomized, placebo-controlled ERT trial of 0.2 mg/kg of alpha-galactosidase A (agalsidase-alfa) every 2 weeks followed by an additional 12 months of open-label ERT for both populations. IENFD and thermal threshold were measured in the distal thigh at baseline, 6 months, and 18 months from initiation of the trial. We found no significant difference in IENFD between the treatment groups at 6 months. After an additional year of ERT, there was a significant reduction in IENFD in the patient group as a whole, attributable to the declining glomerular filtration rate. Thermal thresholds remained unchanged. We conclude that epidermal nerve fiber regeneration, as measured in the distal thigh, does not occur in this patient population after 12-18 months of ERT.  相似文献   

13.

Introduction

Hereditary transthyretin amyloidosis polyneuropathy (ATTRv-PN) presymptomatic carriers often show preclinical abnormalities at small fiber-related diagnostic tests. However, no validated biomarker is currently available to use for presymptomatic carriers' follow-up, thus helping therapeutic decision making. Our study aimed at assessing nerve conduction study (NCS), quantitative sensory testing (QST), and skin biopsy parameters in a large cohort of late-onset ATTRv presymptomatic carriers and to evaluate whether they correlated with predicted age of disease onset (PADO).

Methods

Late-onset ATTRv presymptomatic carriers were consecutively enrolled and underwent NCS, QST, and skin biopsy with intraepidermal nerve fiber density (IENFD) evaluation from a distal and a proximal site. Douleur Neuropathique-4 (DN4) and Small Fiber Neuropathy-Symptoms Inventory (SFN-SIQ) were used to assess painful and small fiber neuropathy-related symptoms. PADO and time-to-PADO (delta-PADO) were estimated for each carrier, and correlations with diagnostic test measures were analyzed.

Results

Forty presymptomatic ATTRv subjects were enrolled. Twenty carriers (50%) had distal IENFD reduction, with a non-length-dependent distribution in 73% of cases. Eleven subjects (27.5%) had cold and/or warm detection threshold (CDT and/or WDT) abnormalities at QST. Delta-PADO positively correlated with sural sensory nerve action potential (SNAP) amplitude (r = .416, p = .004), and z-values of QST parameters like CDT (r = .314, p = .028), WDT (r = −.294, p = .034), and mechanical detection threshold (MDT; r = −.382, p = .012). Simple linear regression models showed a linear relation between delta-PADO and sural SAP, CDT, and MDT.

Conclusions

Our findings confirm that IENFD reduction and QST abnormalities may occur early in ATTRv presymptomatic carriers, often with a non-length-dependent pattern. However, only sural SAP amplitude and QST parameters correlated with delta-PADO, suggesting that serial combined QST and NCS evaluation could be useful in ATTRv presymptomatic carriers' follow-up.  相似文献   

14.
We evaluated the diagnostic sensitivity of quantitative sensory testing (QST), using the CASE IV system, in 14 patients with clinically diagnosed small-fiber neuropathy and normal traditional electrodiagnostic studies. All patients had at least 1 abnormal threshold, 13 patients had abnormal heat-pain thresholds, 8 had abnormal cold thresholds, and 7 had abnormal vibration thresholds. QST is therefore highly effective in documenting dysfunction in small fiber neuropathy patients.  相似文献   

15.
Introduction: Muscle cramps are a common complaint and are thought to arise from spontaneous discharges of the motor nerve terminal. Polyneuropathy is often causative, but small‐fiber neuropathy (SFN) has not been assessed. Methods: We performed skin biopsies on consecutive patients with cramps but without neuropathic complaints. Twelve patients were biopsied, 8 with normal small‐fiber sensation. Results: Seven patients had decreased intraepidermal nerve fiber density (IENFD), 2 with non–length‐dependent loss. A cause for neuropathy was found in 1 patient with cramp–fasciculation syndrome. Creatine kinase was elevated in 8 patients, 4 with decreased IENFD. Muscle biopsy, performed in 8 patients, but was diagnostic in only 1, with McArdle disease. Conclusions: Our data show that 60% of patients with muscle cramps who lack neuropathic complaints have SFN, as documented by decreased IENFD. Cramps may originate as local mediators of inflammation released by damaged small nerve that excite intramuscular nerves. Muscle Nerve, 48: 252–255, 2013  相似文献   

16.
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.  相似文献   

17.
Painful diabetic neuropathy (PDN) is a common, yet devastating complication of type 2 diabetes. At this time, there is no objective test for diagnosing PDN. In the current study, we measured the peptidergic intraepidermal nerve fiber densities (IENFD) from hind paws of the db/db mouse, an animal model for type 2 diabetes, during the period of mechanical allodynia from 6 to 12 weeks of age. Intraepidermal nerve fibers (IENF) of the hind footpads were identified by protein gene product (PGP) 9.5 immunohistochemistry. The peptidergic IENF were determined by double immunofluorescence using anti-PGP9.5 and antibodies against tropomyosin-receptor-kinase (Trk) A. We observed a significant increase in PGP9.5-positive IENFD at 8 and 10 weeks of age. Similarly, Trk A-positive peptidergic IENF, which also express substance P and calcitonin gene related peptide in db/db mice, were observed to be elevated from 1.5 to 2 fold over controls. This upregulation ended at 16 weeks of age, in accordance with the reduction of mechanical allodynia. Anti-NGF treatment significantly inhibited the upregulation of peptidergic IENFD during the period of mechanical allodynia, suggesting that increased neurotrophism may mediate this phenomenon. In addition, SB203580, an inhibitor of p38, blocked the increase in peptidergic IENFD in db/db mice. The current results suggest that peptidergic IENFD could be a potential diagnostic indicator for PDN in type 2 diabetes. Furthermore, the inhibition of NGF-p38 signaling could be a potential therapeutic strategy for treating this painful condition.  相似文献   

18.
Transthyretin amyloid neuropathy of type 1 (Swedish-Portuguese type) is an autosomally inherited progressive disease with a Val30Met mutation, causing generalized sensory-motor polyneuropathy. Quantitative sensory testing (QST) quantifies thermal threshold changes in patients with manifest general polyneuropathy, but its applicability at an early clinical stage of a strict biochemically defined disease has not yet been shown. Thermal QST was performed in 23 patients having a positive Val30Met marker and clinical symptoms of peripheral small-fiber neuropathy but normal electrophysiological findings and compared to a reference group of 43 healthy volunteers, both subdivided into age groups < or =45 and >45 years. Significant differences between patients and controls were found at all test sites in both age groups, except for warm thresholds at the medial lower leg in those >45 years. QST thus demonstrated elevated thermal thresholds before the development of electrophysiological abnormalities, which indicate large-fiber involvement. These findings confirm that QST is a useful method for documentation of developing polyneuropathy.  相似文献   

19.
We administered either 1 or 3 g/d of pyridoxine (vitamin B6) to five healthy volunteers and repeatedly followed serum pyridoxal phosphate levels, clinical symptoms and signs, quantitative sensory thresholds (QSTs), and sural nerve electrophysiology. Pyridoxine was discontinued at the first sign of either clinical or laboratory abnormality. In all subjects, sensory symptoms and QST abnormalities occurred concurrently. Subjects receiving higher doses became symptomatic earlier than low-dose subjects. Elevation of thermal QSTs preceded or exceeded that for vibration in the three low-dose subjects; vibration and thermal QST became abnormal simultaneously in the higher-dose subjects. A reduction in the amplitude of the sural sensory potential lagged behind QST changes in two of three subjects. Symptoms continued to progress ("coasting") for 2 to 3 weeks despite stopping pyridoxine administration and the return of serum pyridoxal phosphate levels to normal. This study suggests that (1) there is a clear dose-percent relationship for pyridoxine-induced neuropathy, (2) QST is a sensitive measurement for detecting early peripheral neuropathy; QST abnormalities may precede changes in nerve conduction studies, (3) coasting appears unrelated to persistently elevated blood levels of the toxin, and (4) a dose-dependent vulnerability may exist among nerve fibers of different caliber when exposed to an axonal toxin, such as pyridoxine.  相似文献   

20.
目的探讨糖尿病(DM)病程对糖尿病周围神经病变(DPN)严重程度及下肢周围神经显微减压术疗效的影响,以及糖尿病周围神经病变早期诊断、早期手术的意义。方法以5年糖尿病痛程作为标准,将我科近年收治的1526例糖尿痛周围神经病患者分为短DM病程组和长DM病程组,按Dellon术式对卡压的神经进行下肢周围神经显微减压术。所有患者术前、术后1.5年进行神经高频超声、定量感觉检查(QST)、神经感觉传导速度(NCV)检测,并选取50例正常人群作为对照组检测相同指标。结果与对照组相比,DPN患者的NCV、冷感觉阈值较低,热感觉阈值、振动觉阈值及神经横断面积(CSA)较高,差异有统计学意义(P〈0.05)。患者术后各项指标明显改善,与术前相比,差异有统计学意义(P〈0.05)。短DM病程DPN患者术前和术后各指标均优于长DM病程DPN患者,两组比较差异有统计学意义(P〈0.05)。短DM病程DPN患者NCV阳性检测率为71.5%,QST阳性检测率为93.7%;长DM病程DPN患者NCV阳性检测率为90.3%,QST阳性检测率为95.3%。结论糖尿病痛程对DPN患者发病时的严重程度至关重要,同时也对DPN患者的手术疗效和预后产生影响。DPN的早期诊断、早期手术具有重要临床价值。  相似文献   

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