Small Fiber Impairment Research Articles

Effect of Lead Exposure and Ergonomic Stressors on Peripheral Nerve Function

In this study we investigated the effect of recent and chronic lead exposure, and its interaction with ergonomic stressors, on peripheral nerve function. In a cross-sectional design, we used retrospective exposure data on 74 primary lead smelter workers. We measured blood and bone lead levels and, from historical records, calculated lead dose metrics reflecting cumulative lead exposure: working-lifetime integrated blood lead (IBL) and working-lifetime weighted-average blood lead (TWA). We additionally created five metrics related to IBL that cumulated exposure only above increasing blood lead levels ranging from 20 to 60 μg/dL (IBL20–IBL60). Current perception threshold (CPT) assessed large myelinated (CPT2000), small myelinated (CPT250), and unmyelinated (CPT5) sensory nerve fibers. Using multiple linear regression, we modeled CPT on the different measures of lead dose after adjusting for relevant covariates. CPT had a curvilinear relationship with TWA, with a minimum at a TWA of 28 μg/dL. Both TWA and IBL accounted for a significant percentage of the variance of CPT2000 (ΔR2 = 8.7% and 3.9%, respectively). As the criterion blood lead level increased from IBL20 through IBL60, so did the percentage of CPT2000 variance explained, with ΔR2 ranging from 5.8% (p < 0.03) for IBL20 to 23.3% (p < 0.00) for IBL60. IBL60 also significantly contributed to the explanation of variance of CPT250 and significantly interacted with ergonomic stressors. Measures of chronic blood lead exposure are associated with impairment of large and small myelinated sensory nerve fibers. This effect is enhanced at the highest doses by ergonomic stressors.

Time Sequence of Sensory Changes after Upper Extremity Block

Sensory assessment to estimate spread and effectiveness of a peripheral nerve block is difficult because no clinical test is specific for small sensory fibers. Occurrence of a swelling illusion (SI) during a peripheral nerve block corresponds to the impairment of small sensory fibers. The authors investigated the usefulness of SI in predicting successful peripheral nerve block by assessing the temporospatial correlation between progression of sensory impairment in cutaneous distributions anesthetized and localization of SI during peripheral nerve block installation. Interscalene, infracoracoid, or sciatic nerve blocks were performed using a nerve stimulator and 1.5% mepivacaine in 53 patients, with a total of 201 nerves to be anesthetized. Pinprick, cold, warm, touch, and proprioception were assessed every 3 min, while patients were asked to describe their perception of size and shape of their anesthetized limb and localization of these illusions. Data are presented as mean +/- SD and percentage (95% confidence interval). Failure occurred in 12 cutaneous distributions out of a total of 201 theoretically blocked nerves. SI appeared earlier than warmth impairment (4.3 +/- 2.7 vs. 6.2 +/- 2.0 min; P < 0.05), always corresponding to successfully anesthetized cutaneous distributions, with the exception of 1 patient, who developed SI in 2 cutaneous distributions while sensory testing indicated failure in 1 distribution. SI successfully predicted the blockade of a cutaneous distribution with a sensitivity of 1.00 (0.98-1.00), a specificity of 0.92 (0.65-0.99), and an accuracy of 0.99 (0.97-1.00). Swelling illusion may provide an early assessment of the success of a peripheral nerve block in unsedated patients.

Skin denervation in type 2 diabetes: correlations with diabetic duration and functional impairments.

Sensory neuropathy is a prominent component of diabetic neuropathy. It is not entirely clear how diabetes influences skin innervation, and whether these changes are correlated with clinical signs and laboratory findings. To investigate these issues, we performed skin biopsies on the distal leg of 38 consecutive type 2 diabetic patients with sensory symptoms in lower limbs (25 males and 13 females, aged 56.2 +/- 9.4 years) and analysed the correlations of intraepidermal nerve fibre (IENF) densities in skin with glycaemic status (duration of diabetes, HbA1C, and fasting and post-prandial glucose levels), and functional parameters of small fibres (warm and cold thresholds) and large fibres (vibratory threshold and parameters of nerve conduction studies). Clinically, 23 patients (60.5%) had signs of small-fibre impairment, and 19 patients (50.0%) had signs of large-fibre impairment. IENF densities were much lower in diabetic patients than in age- and gender-matched controls (1.794 +/- 2.120 versus 9.359 +/- 3.466 fibres/mm, P < 0.0001), and 81.6% (31/38) of diabetic patients had reduced IENF densities. IENF densities were negatively associated with the duration of diabetes (standardized coefficient: -0.422, P = 0.015) by analysis with a multivariate linear regression model. Abnormal results of functional examinations were present in 81.6% (warm threshold), 57.9% (cold threshold), 63.2% (vibratory threshold) and 49% (amplitude of sural sensory action potential) of diabetic patients. Among the three sensory thresholds, the warm threshold temperature had the highest correlation with IENF densities (standardized coefficient: -0.773, P < 0.0001). On nerve conduction studies in lower-limb nerves, there were abnormal responses in 54.1% of sural nerves, and 50.0% of peroneal nerves. Of neurophysiological parameters, the amplitude of the sural sensory action potential had the highest correlation with IENF density (standardized coefficient: 0.739, P < 0.0001). On clinical examination, 15 patients showed no sign of small-fibre impairment, but seven of these patients had reduced IENF densities. In conclusion, small-fibre sensory neuropathy presenting with reduced IENF densities and correlated elevation of warm thresholds is a major manifestation of type 2 diabetes. In addition, the extent of skin denervation increases with diabetic duration.

Neurophysiological studies of thin myelinated (A delta) and unmyelinated (C) fibers: application to peripheral neuropathies

Dysfunction of small fibers may appear in isolation or associated with large fiber lesions. In some acute neuropathies, such as pandysautonomia, small-fiber impairment is relatively pure but it may also appear in disorders with prominent somatic damage, such as Guillain-Barré syndrome, in which autonomic failure worsens the prognosis. At the present time, chronic idiopathic distal small-fiber neuropathy is diagnosed more frequently, and in some prevalent disorders, such as diabetic or amyloidotic polyneuropathies, small-fiber dysfunction is very noticeable. In pure autonomic failure, a peripheral autonomic failure exists, distinguishing it from multiple-system atrophy. Complex regional pain syndrome is a severe condition in which small fibers are responsible for disabling signs and symptoms, and only instrumental recordings lead to the proper treatment. Standard neurophysiological techniques evaluate large myelinated fibers exclusively. Small-fiber polyneuropathy has been considered as a type of somatic neuropathy, but thin myelinated and unmyelinated fibers are responsible not only for temperature and pain perception but also autonomic function. For instance, full autonomic evaluation is needed in some clinical situations such as autonomic failure in the elderly or orthostatic intolerance syndrome. To evaluate small-fiber impairment we need a battery of sensitive, reproducible, specific and noninvasive tests covering somatic and autonomic systems. In this review, we describe and analyze a number of neurophysiological techniques used to diagnose and characterize small-fiber dysfunction in humans. These include cardiovascular monitoring, sudomotor testing, pupillary responses and quantitative sensory tests, and also to some extent thermography and laser evoked potentials. The use of such techniques has proven useful not only for diagnosis, but also to guide adequate therapy and optimize follow-up.

Modelling of Thermal Hyperemia in the Skin of Type 2 Diabetic Patients

The microcirculatory response to thermal stimulation involves both an axon reflex and NO-mediated activation. The analysis of the microcirculatory flow following thermal stimulation may therefore enhance the detection of any impairment of the small unmyelinated fibres that are involved in the axon reflex. The aim of this work is to establish a method of non-invasive measurement of small fibre impairment. The microcirculatory flow in response to local heating is measured by using a laser Doppler instrument, and mathematically modelled to extract a set of quantitative parameters. The results confirm that there is a significant difference in the parameters modelling the axon reflex between diabetic and control subjects, while no significant difference is found in the parameters modelling the NO-mediated activation.

PS-51-1 Pain in painful diabetic neuropathy depends on impairment of small somatosensoric nerve fibers

PS-51-1 Pain in painful diabetic neuropathy depends on impairment of small somatosensoric nerve fibers