Effect of perinatal food deficiencies on the compound action potential evoked in sensory nerves of developing rats

The aim of this study was to analyze the possible alterations produced by inadequate perinatal food intake, in quantity (undernutrition) or quality (malnutrition), on the generation and propagation of the compound action potential (CAP) evoked in sensory sural nerves, during the postnatal development of the rat. Low intensity stimulation (2-3 times the threshold of the most excitable nerve fibers; xT) of the sural nerve evoked an early potential (CAP-A component) which is due to activation of low-threshold, fast-conducting myelinated group A afferent fibers. Meanwhile, at higher stimulus intensity (20-30T) it produced a second, long-lasting potential (CAP-C component) probably due to activation of high-threshold, slow-conducting group Adelta or C afferent fibers. Compared to control nerves, the CAP-A component, but not the CAP-C component of undernourished and malnourished nerves showed significant changes in amplitude, area, electrical threshold and conduction velocity (except absolute refractory period) at several postnatal ages. Our results may suggest that a relative large number of myelinated group A afferent fibers in the sural nerve of undernourished and malnourished animals suffer severe alterations on their electrophysiological properties of generation and propagation of the action potential during the postnatal development of the rat.     

Morphometric analysis of normal human sural nerves for systematic clinical application]

To obtain normative data on the sural nerve for clinical evaluation of the pathologic process and severity of the various peripheral nerve disorders, a morphometric analysis was made on 30 control sural nerves from normal volunteers, and from patients and cadavers with no evidence of peripheral nerve involvement. The ages of volunteers, patients and cadavers ranged from 13 to 83 years. The data obtained included 1) the mean frequency of abnormal teased myelinated fibers and its upper limit value of 95% confidence interval, and 2) the mean densities of total, large and small myelinated fibers and of unmyelinated fibers and their lower limit value of 95% confidence interval for each decade. The linear correlation between the age and each of the frequencies of abnormal teased myelinated fibers and the densities of total, large and small myelinated fibers and of unmyelinated fibers were statistically significant (P less than 0.01). Therefore, the morphometric data obtained from the disease nerve should be compared with the normative data adjusted for the age of the subject described in this study.     

Hypertrophic neuropathy with diabetes mellitus

A 52-year-old male with diabetes mellitus showed sensorimotor disturbance of symmetrical glove and stocking distribution. Electromyography demonstrated signs of denervation, and motor nerve conduction velocities could not be obtained because the muscle action potential was not evoked by the electrical stimulation of the nerves. Quantitative histologic and ultrastructual studies were performed in the sural nerve biopsy. Determination of fiber densities revealed a striking decrease of both myelinated and unmyelinated fibers and remarkable increase of the onion bulb formations. Hypertrophic changes with onion bulb formations have been observed in various clinical conditions, particularly in hereditary disorders, but uncommon in diabetic neuropathy. Our case was non-familial and may form one atypical type of diabetic neuropathy.     

Small axons relative to number of myelin lamellae in Charcot-Marie-Tooth disease 1A with peripheral myelin protein 22 gene duplication

In myelinated fibers of the sural nerves in Charcot-Marie-Tooth disease 1A (CMT 1A), with peripheral myelin protein (PMP) 22 gene duplication, it has been controversial whether axonal attenuation occurs or the myelin sheath thickens. Therefore, the relationship between the transverse axonal area and the number of myelin lamellae was morphometrically studied in myelinated fibers of the sural nerves in CMT 1A with PMP22 gene duplication to re-evaluate such relationships as are revealed in hereditary motor sensory neuropathy, type 1 without genetic diagnosis. In electron microscopic studies both the axonal circumference and natural log (ln) axonal area were significantly (P < 0.01) smaller in the CMT 1A group (n = 8) than in the control group (n = 9). Myelin lamellae numbers, however, were similar in both groups. In a regression analysis relating ln axonal areas to the numbers of myelin lamellae, ln axonal area in the CMT 1A group was significantly (P < 0.05) smaller than in the control group in myelinated fibers with the numbers of myelin lamellae equal to or over 40. Therefore, it was concluded that the axonal area was smaller in large-diameter myelinated fibers in the CMT 1A group than in the control group. We speculated on the existence of axonal attenuation due to the impaired effect of Schwann cells on myelinated axons in CMT 1A with PMP22 gene duplication.     

Quantitative ultrastructural evidence of myelin malformation in optic nerves of rats submitted to a multideficient diet

Pups were subjected to malnutrition by feeding the lactating mothers a multi-deficient (8% protein content) diet, known as regional basic diet (RBD), from birth up to weaning. The weanings were fed the same diet until 60 days of age. Ultrastructure of the optic nerve was analyzed at postnatal (P) day P8, P13, P21, P30 and P60. Electron microscopy revealed that at P8 the process of myelination has not started yet in neither groups. At P 13 different stages of myelination were observed and, in the experimental group, the optic nerve showed non-organized axon bundles and empty spaces. Control optic nerve at P21 exhibited axons with fully developed myelin sheath; whereas malnourished group had many axons being enveloped by myelin with anomalous alteration. These alterations were present in malnourished group at P30 and P60. Quantitative analysis showed statistically significant difference between control and malnourished groups when compared to the percentage of myelinated axons, axons with myelin anomalous alterations (MAA) and non-myelinated axons. Also, the myelin area was significantly smaller in malnourished groups when compared to control group. Finally, a high percentage of large non-myelinated fibers were found in the malnourished group. In conclusion, our results show that early malnutrition by a multideficient diet (RBD) affects permanently the optic nerve organization and myelination, indicating an impairment of nerve transmission and a probable dysfunction in the visual ability.     

Electrophysiology and nerve biopsy in men exposed to lead

ABSTRACT Twenty lead-exposed men were selected on the basis of a maximum level of lead in the blood of 70-140 μg/100 ml within the past year. There was no clinical evidence of neuropathy attributable to lead and haemoglobin levels were normal. In individuals, maximum motor and sensory conduction and the amplitude of the evoked potentials were normal or borderline in the median, peroneal and sural nerves, except in the distal portion of the deep peroneal nerve. In this nerve, motor conduction was slowed because of compression by metal-lined safety shoes; changes in this segment are not included in the findings. When the average conduction velocity in lead-exposed men was compared with the average in nerves of controls matched for age, distal motor latency was slightly prolonged in the median nerve. The average latency for proximal muscle supplied by the peroneal nerve was prolonged, and the maximum motor conduction velocity was slowed in the median nerve from elbow to wrist (0·01 > p <0·001). In addition, the average maximum sensory conduction was slightly slowed along the distal and intermediate portion of the superficial peroneal and sural nerves (p <0·001). The average minimum sensory conduction velocities were normal, as were the average amplitudes of the evoked muscle action potentials and the average ratio of amplitude of the muscle action potential evoked by stimuli at a proximal and a distal nerve site. The average amplitude of the sensory potentials recorded in the median and the superficial peroneal nerves tended to be increased. Electromyography of the abductor pollicis brevis and anterior tibial muscles showed that the only abnormality was an increased incidence of polyphasic potentials in the anterior tibial muscle of seven men. Neither the slowing in conduction nor the histological findings in the sural nerves of eight men were related to the level of lead in the blood. The slight slowing in conduction suggests a minor defect in the excitable membrane of the nerve fibre: it was not attributable to histological abnormalities in the sural nerve, in which the number of myelinated and unmyelinated nerve fibres was normal and demyelination was absent. In teased fibres, those with paranodal remyelination were slightly increased, and few fibres had segments with diminished diameter. The mechanism of the defect causing the slight slowing in conduction in lead-exposed men seems to differ from the lesion in patients with clinical evidence of lead neuropathy, which is axonal in type. It is, therefore, doubtful whether the slight slowing in the nerves of the group of lead-exposed men should be classified as a subclinical neuropathy.     

Pathologic processes of lumbar primary sensory neurons produced by high doses of pyridoxine in rats--morphometric and electron microscopic studies

The morphologic effects of the toxicity of high doses of pyridoxine hydrochloride (vitamin B6) on the lumbar primary sensory neurons in rats were studied. The test rats were treated with 1,200 mg/kg of pyridoxine hydrochloride by intraperitoneal injection once a day, and were sacrificed by perfusion at periods ranging from one to seven days after the injection, together with the control rats. Initial lesions consisted of eccentricity and crenation of the nucleus and vacuole formation in the cytoplasm of large dorsal root ganglion neurons, 2 days after the injection. These lesions were followed by segregation of the nucleolus, axon reaction-like changes in the cytoplasm and axonal degeneration of both peripheral axons in the sural nerve and central axons in the fasciculus gracilis. The frequency of teased myelinated fibers showing axonal degeneration during tests was significantly greater than in control 3 to 7 days after the injection. No significant difference of such frequency was found between the proximal and distal sural nerve during tests. The number of large myelinated fibers per nerve in the sural nerve, when compared with control, was preferentially decreased during tests. In the fasciculus gracilis, the decrease of the density of myelinated fibers was more pronounced in the third cervical segment than in the fifth thoracic segment. Because both peripheral and central axons were similarly affected and the initial lesions were found in the neuronal cell body, the mode of degeneration of axons in this study was regarded as "neuronopathy". By both light and electron microscopy, accumulation of mitochondria, vesicles, multilamellar and dense bodies were found in the nodal and distal paranodal axons of myelinated fibers in the sixth dorsal root ganglion on the 2nd day after the injection, which preceded the degeneration of both peripheral and central axons. Such accumulation, revealed for the first time in this study, may reflect the presence of a blockade of the axoplasmic transport in the proximal axon and cell body of the lumbar primary sensory neuron and subsequently give rise to the degeneration of both peripheral and central axons of the lumbar primary sensory neuron. The pathologic alterations at the different sites of the lumbar primary sensory neuron revealed in this study should be taken into consideration for the better understanding not only of the pathogenesis of human pyridoxine-induced sensory neuropathy, but also of other human and experimental neuropathies.     

Neurophysiological studies on workers exposed to lead.

Nerve conduction and somatosensory evoked potential studies were undertaken on 46 workers exposed to a combination of organic and inorganic lead. In addition electroencephalograms were carried out on 20 of the workers; the results were compared with those obtained for workers not exposed to lead. The workers exposed to lead had a mean blood lead concentration of 2.35 mumol/l (48.7 micrograms/100 ml), whereas the concentration for workers not exposed to lead was 0.76 mumol/l (15.8 micrograms/100 ml). The mean maximum motor conduction velocities of the median and the posterior tibial nerves were significantly lower in the workers exposed to lead than in the controls. Similarly, the distal latency for these two nerves was significantly prolonged for the workers exposed to lead. No significant differences for the two groups of workers were seen in the nerve conduction and distal latency measurements of the median (sensory) and the sural nerves. The EEG studies of the 20 workers exposed to lead showed no abnormalities. The somatosensory evoked potential of the median (sensory) and posterior tibial nerves were significantly prolonged when measured at the negative and positive deflections. The results suggest that, in addition to nerve conduction velocities, somatosensory evoked potential and distal latency are suitable measurements to detect subclinical neurological damage among workers exposed to lead. As these changes were seen at blood lead concentrations of 2.35 mumol/l (48.7 micrograms/100 ml) there may be a need for more stringent monitoring of workers exposed to lead.     

Neurophysiological studies on workers exposed to lead

Nerve conduction and somatosensory evoked potential studies were undertaken on 46 workers exposed to a combination of organic and inorganic lead. In addition electroencephalograms were carried out on 20 of the workers; the results were compared with those obtained for workers not exposed to lead. The workers exposed to lead had a mean blood lead concentration of 2.35 mumol/l (48.7 micrograms/100 ml), whereas the concentration for workers not exposed to lead was 0.76 mumol/l (15.8 micrograms/100 ml). The mean maximum motor conduction velocities of the median and the posterior tibial nerves were significantly lower in the workers exposed to lead than in the controls. Similarly, the distal latency for these two nerves was significantly prolonged for the workers exposed to lead. No significant differences for the two groups of workers were seen in the nerve conduction and distal latency measurements of the median (sensory) and the sural nerves. The EEG studies of the 20 workers exposed to lead showed no abnormalities. The somatosensory evoked potential of the median (sensory) and posterior tibial nerves were significantly prolonged when measured at the negative and positive deflections. The results suggest that, in addition to nerve conduction velocities, somatosensory evoked potential and distal latency are suitable measurements to detect subclinical neurological damage among workers exposed to lead. As these changes were seen at blood lead concentrations of 2.35 mumol/l (48.7 micrograms/100 ml) there may be a need for more stringent monitoring of workers exposed to lead.     

感觉统合失调儿童感觉神经传导状况的研究

目的 定量评估感觉统合失调(SID)儿童与正常儿童间感觉神经纤维传导的差异状况。方法 采用感觉电流阈值(CPT)评估法,对128例SID儿童和96例正常儿童的双侧三叉神经、正中神经和腓浅神经的感觉神经粗有髓鞘纤维(Aβ)、细有髓鞘纤维(Aδ)和无髓鞘纤维(C)进行2 000、250 Hz和5 Hz三种不同强度的感觉电流阈值测试。结果 1)SID儿童感觉异常情况:三叉神经的感觉异常率最高(左侧63.28%,右侧72.66%),左右两侧的三叉神经与正中神经在2 000、250 Hz和5 Hz三种强度下的感觉异常率差异有统计学意义(P<0.05),而腓浅神经差异无统计学意义。2)两组儿童不同部位CPT的差异:SID儿童在正中神经、腓浅神经2 000 Hz、250 Hz的CPT较正常儿童高,两者在2 000 Hz差异有统计学意义(P<0.05)。3)感统得分与CPT的相关性:SID儿童的感统得分与不同部位2 000 Hz、250 Hz的CPT呈负相关(P<0.05)。结论 与正常儿童相比较,SID儿童感觉神经传导功能存在异常,以粗有髓鞘纤维(Aβ)和细有髓鞘纤维(Aδ)更为明显。     

Electroneurographic findings in patients with solvent induced central nervous system dysfunction.

The function of the peripheral nervous system was examined in a group of 32 men aged 30-65 (mean 49) with diagnosed solvent induced chronic toxic encephalopathy. The subjects were examined at the time of diagnosis and 26 were re-examined after a follow up period of 22-72 months (mean 40) and compared with a group of 50 unexposed male workers aged 27-64 (mean 42) with appropriate adjustment for age. All subjects were carefully scrutinised for alcohol abuse and other neurological diseases. The results of motor fibre neurography disclosed no difference between the groups. Nevertheless, a significant decrease in motor conduction velocity was found in the patients at follow up. Sensory fibre neurography showed signs of slight axonal degeneration with significantly decreased sensory nerve action potential amplitudes in the median and sural nerves; these amplitudes increased during follow up. The duration of sensory nerve action potentials was longer in the exposed group for the median and the sural nerves. The percentage of late components was significantly higher in the median nerve. The warm-cold sensitivity in the exposed group also indicated a slight sensory dysfunction with statistically significant wider detection limits.     

Occupational exposure to pesticides and nerve conduction studies among Korean farmers

This study aimed to determine whether occupational exposure to pesticides was associated with decreased nerve conduction studies among farmers. On 2 separate occasions, the authors performed a cross-sectional study of a group of 31 male farmers who periodically applied pesticides. The study included questionnaire interviews and nerve conduction studies on the median, ulnar, posterior tibial, peroneal, and sural nerves. Although all mean values remained within laboratory normal limits, significant differences between the first and second tests were found in sensory conduction velocities on the median and sural nerves, and motor conduction velocities on the posterior tibial nerve. Lifetime days of pesticide application was negatively associated with nerve conduction velocities at most nerves after adjusting for potential confounders. These findings may reflect a link between occupational pesticide exposure and peripheral neurophysiologic abnormality that deserves further evaluation.     

丙烯酰胺中毒后小鼠周围神经逆行性坏死的实验病理研究

目的 观察丙烯酰胺（ACR）中毒后变异的C57BL／Ola（Ola）鼠与正常的C57BL／6J（6J）鼠轴突逆行性坏死的病理改变及责任中鼠的不同点;探讨轴突与神经元损伤的关系。方法 利用光镜和电镜技术对腓神经、腓肠神经及背根神经节神经元的改变进行定性和定量分析。结果 光镜下6J鼠总纤维面积明显增大,纤维密度明显降低,大径纤维减少;轴突肿胀,髓鞘深染,形状不规划。背根神经节中一些亮细胞（A型细胞）核偏向一侧,胞浆内有一些暗颗粒。电镜下见轴突内神经微丝增多,线粒体堆积。背根神经节细胞胞浆内线粒体呈空泡样或凝聚样变性。Ola鼠未见明显改变。结论 Ola鼠对ACR所致的类化勒氏变性反应是延迟的,而6J鼠中毒后出现轴突肿胀、变性,电镜下神经微丝的聚集、线粒体堆积为特征;ACR先侵犯神经元,继之产生远端轴突变性。     

Structural aspects of experimental carbon disulfide neuropathy

Summary In white rats exposed to CS₂ vapors (at the average concentration of 1.5 mg per liter of air) over 1 to 15 months, the progressive development of structural lesions was studied in the selected areas of the central and peripheral nervous system. Gradual destruction of myelinated fibers within the white matter of spinal cord and in the peripheral nerves was observed. Morphological alterations of the body of the nerve cells were also encountered, but their pathologic nature and their relation to the exposure were disputable even at the stage of advanced CS₂ induced myelo- and neuropathy.This investigation has been done under the Polish-American agreement No. 05-003-3 with the Occupational Health Program, U.S. Public Health Service.     

Assessment of the peripheral, central, and autonomic nervous system function in styrene workers.

To investigate the effects of styrene exposure on peripheral, central, and autonomic nervous system functions in man, we measured the distribution of nerve conduction velocities (DCV), short-latency somatosensory evoked potentials (SSEP), and variability in electrocardiographic R-R interval (CVRR) as well as conventional sensory and motor median nerve conduction velocities (SCV and MCV) in eleven styrene-exposed workers. The styrene workers' urinary phenylglyoxylic acid levels ranged from 31 to 419 (mean 169) mg/g creatinine at the end of the work shift on the examination day (estimated exposure to styrene of 22 ppm in air). Control subjects, matched to each styrene worker by sex and age, were selected from healthy adults without cardiovascular, neurologic and other potentially confounding disorders. In the styrene workers, we found that the V80 velocity of the DCV, below which 80% of active nerve fibers lie, and the SCV were both significantly slowed; the CVRR was also significantly reduced. There were no significant differences in SSEP latencies, MCV, or heart rate between the exposed workers and controls. These data, despite the small sample size, suggest that styrene affects the faster myelinated fibers of the peripheral sensory nerves, and that it also affects autonomic nervous activity.     

Ultrastructural changes of cutaneous nerves in scleroderma.

Ultrastructural changes in cutaneous nerves of 38 patients with progressive scleroderma and eight patients with circumscribed scleroderma are described in the present study. Changes in the myelinated as well as in the unmyelinated fibers were observed in all cases. Myelinated fibers exhibited progressive disintegration of their myelin sheaths. Edema of the cytoplasm and various lesions of the organelles were observed in the Schwann cells. The basal membranes of both myelinated and unmyelinated fibers were irregularly thickened and flimsy in appearance. The axis cylinders were affected to a lesser extent. Edema of the axoplasm, and, less often, reduction of the number of neurofibrils and microtubules were observed there. Sometimes, the nerve fibers were enwrapped compactly by a considerable amount of collagen fibrils. The observed changes of the peripheral skin nerves are very often secondary. They are the morphologic basis of a limited or generalized neuropathy which sometimes develops.     

Nerve conduction velocity studies of workers employed in the manufacture of phenoxy herbicides

Conduction velocities (NCV) of the median motor, median sensory, and sural nerves were measured in 56 workers employed in the manufacture of 2,4,5-trichlorophenoxy acetic acid (2,4,5-T) and 2,4-dichlorophenoxy acetic acid (2,4-D). Mean age was 35 years and mean duration of employment was 7 years. The control group consisted of 25 subjects without exposure to neurotoxic agents. When compared with controls, slowing was noted in the sural nerve (mean = 34.0 vs 40.1 m/sec, P > 0.02). All values were then adjusted for age and temperature and were transformed to Z values (mean = 0, standard deviation = 1), where-upon slowing was seen in the sural (?2.21 vs ?0.52, P < 0.0001) and median motor nerves (0.19 vs 0.91, P < 0.03). Duration of employment was significantly correlated with slowing of sural velocity (r = ?0.40, P < 0.004). Altogether, 46% of the study group had one or more slowed nerve conduction velocity, versus 5% of the control group P < 0.001).     

Variability of quantitative sensory testing: implications for clinical practice

The conventional estimation of motor, sensory, and mixed nerve conduction velocities reflects activity in the fastest conducting, heavily myelinated nerve fibers that are only a small proportion of the total. Unmyelinated and thinly myelinated fibers are not evaluated by this technique and numerically represent the largest group of fibers in human cutaneous nerves. The availability of new quantitative techniques to study this aspect of sensory function is an important addition to standard electrodiagnosis. Patient understanding and cooperation is essential because subjective responses are evaluated. We evaluated a reference range for 20 healthy subjects as well as variability on repeated testing. Vibration and thermal thresholds were measured bilaterally at several sites. Measurements were repeated at intervals ranging from two days to three months. There was no side difference but substantial site differences were noted for all measurements. Intraindividual variation was substantial but within the expected range for a psychophysiologic test. Close correlation was noted between various measurements at same and different sites, indicating a great degree of interindividual variation. The Marstock method is recommended for routine clinical use.     

Correlation between vibratory detection threshold and conduction study of sural nerve in diabetic patients

Vibratory detection threshold (VDT) was determined on the plantar side of the distal phalanx of the right great toe of 22 diabetic (NIDDM) patients. In addition, a neurological examination and a sural nerve conduction study were performed. Peripheral neuropathy, based on our criteria, was found in 41% of the patients. VDT was abnormally high in 23% of the patients. The combined frequency of the abnormality of the amplitude of the action potential of the sural nerve or the conduction velocity or both was 73%. The nerve conduction study showed the highest sensitivity in detecting the abnormality of the peripheral nerve in this study; this is in agreement with the result shown in the literature. Seven patients showed no response to electrical stimulation of the sural nerve, although VDT was obtained in these patients. Among the 6 patients that underwent the normal sural nerve conduction study, no one showed abnormally high VDT. The determination of VDT seems to be a useful examination for the follow-up study of diabetic neuropathy, although it is less sensitive than the sural nerve conduction study.     

Special nerve functions and colour discrimination in workers with long term low level exposure to carbon disulphide

Certain functions of the peripheral and autonomic nervous systems, and colour discrimination were examined in 45 workers (mean age 49; mean exposure to carbon disulphide (CS2) 20 years) and 37 controls (mean age 48). Conduction velocity and refractory period of the peroneal and sural nerves were determined. The conduction velocity of the slower fibres of the peroneal nerve was measured by means of an improved method that makes use of the refractory period. Function of autonomic nerves was assessed by measuring the variation in heart rate during rest, during deep breathing, and during isometric muscle contraction. Colour discrimination was evaluated by the Lanthony desaturated test. Individual cumulative exposure to CS2 was calculated on the basis of exposure in the past and individual job history. Mean cumulative exposure was 165 ppm-years. The peroneal nerves of exposed workers showed a decrease (-1.0 m/s) in conduction velocity of the slow fibres and a prolongation (0.1 ms) of the refractory period (mean 1.6 ms) compared with controls. These effects were related to cumulative exposure. No impairment of function of the sural nerve or of colour discrimination was found. The muscle heart reflex was decreased in the exposed group, but this was not related to cumulative exposure. This study has established more firmly that a decrease in conduction velocity of slow motor fibres occurs at low levels of exposure to CS2. Extrapolation of the results suggests that small effects may occur after 40 years of exposure to concentrations below the present threshold limit value (10 ppm).