A micro-electrode study of peripheral neuropathy in man. Part 2. Responses to conditioning stimuli.

Surface, needle and micro-electrode recordings were obtained from sensory nerves of patients with various types of peripheral neuropathy. Changes in amplitude and conduction velocity of nerve action potentials were measured after a single conditioning stimulus and after tetanic stimulation for 2 min. In patients with hereditary forms of axonal degeneration (AD), recovery processes of nerve fibres of all conduction velocities were normal; in acquired forms of AD fibres with conduction velocity less than 30 m/sec had greater and more prolonged post-tetanic depression than control nerves of similar conduction velocity. Where neuropathy was associated with segmental demyelination (SD), fibres of all conduction velocities had prolonged recovery processes after both single and tetanic stimulation. The changes were especially marked at higher skin temperature, and were greater than the changes seen in nerves with acquired forms of AD. Finally, 2 sural nerves were studied during the process of Wallerian degeneration after a biopsy had been obtained proximally, and recovery processes did not change during the period of degeneration. Perceptual abnormalities were similar in AD and SD. It is suggested that changes in recovery processes of nerve fibres with segmental demyelination or regeneration after injury contribute to the perceptual abnormalities which occur in clinically encountered peripheral neuropathies.     

Polyneuropathy. Facts and fancies.

Some conclusions are drawn from findings in 167 consecutive patients with the ordinary "garden variety" of polyneuropathy; the aetiology was unknown in 15%. Histological findings in sural nerves were related to clinical and electrophysiological abnormalities. In some patients with discrete clinical abnormalities, sensory and motor conduction and amplitudes of evoked sensory and muscle action potentials were normal, whereas the nerve biopsy showed slight but definite abnormalities. The reverse, abnormal nerve conduction and normal histological findings, did not occur. Histological findings were rarely, and electrophysiological findings were not, specific for the aetiology or type of a neuropathy. Thus, neither conduction studies nor conventional or single fibre electromyography can identify the underlying pathology: loss of large myelinated fibres (greater than 7 micrometers) was equally prominent in nerves with de- and re-myelination as in those without them. Paranodal and segmental demyelination in less than 20% of the teased fibres occurred as often in nerves with as in those without disproportionate slowing in conduction. When the recorded conduction velocity was equal to that to be expected from the fibres with the largest diameter, slowing in conduction could be explained by axonal degeneration ("proportionate" slowing, 79% of the nerves). When the recorded velocity was disproportionately slower than that expected from fibre diameter (21% of the nerves), causes other than loss of the largest fibres must be assumed to explain the slowing in conduction. Myelin abnormalities in more than 50% of the teased fibres were found only in nerves from patients with the hypertrophic type of peroneal muscular atrophy and in postgastrectomy neuropathy and can probably explain the marked disproportionate slowing in conduction. The material contained, however, only one patient with acute idiopathic polyradiculoneuropahy. In diabetic neuropathy, segmental demyelination was present in only 8 of 502 teased fibres (9 nerves), remyelination was present in 135 fibres, and could not explain the disproportionate slowing in conduction. The mechanism of disproportionate slowing, when it is not due to demyelination, is still obscure.     

Peripheral neuropathy following a single exposure to arsenic. Clincal course in four patients with electrophysiological and histological studies.

Four patients are described who developed a peripheral neuropathy 10 days to 3 weeks after ingestion of a single dose of arsenic. All improved slowly, but after 6 to 8 years 3 of them still had abnormal neurological symptoms and signs. Electrophysiological studies showed reduction of motor conduction velocity and marked abnormalities of sensory nerve action potentials. The findings suggest that conduction is abnormal in at least some surviving nerve fibres. Sural nerve biopsies from 2 patients showed axonal degeneration, which was at an early stage in some fibres, even 10 weeks after intoxication.     

Nerve biopsy and conduction studies in diabetic neuropathy.

Morphological findings in sural nerves were related to nerve conduction in 12 patients with diabetic neuropathy, five with mainly sensory involvement, four with severe, symmetrical sensory-motor polyneuropathy, and three with multiple mononeuropathy. All had loss of large and small myelinated and of unmyelinated fibres, even early in the disease; segmental remyelination was the most prominent myelin alteration in teased fibres, segmental demyelination was found in only a few fibres. Axonal degeneration and Schwann cell damage seem to proceed independently of each other. The relation between recorded conduction velocity and that expected from the diameter of the largest fibres indicated that slowing of 20 to 30% was due to causes other than fibre loss; a grossly diminished conduction velocity was caused mainly by fibre loss. Electrophysiological findings in the sural nerve were largely representative of findings in other nerves, though abnormalities were less marked in the median nerve. In half the endoneurial vessels from diabetic neuropathy the perivascular space was thickened or contained more layers of basal laminae than normal. The same abnormalities were found in one-quarter of the endoneurial vessels from other acquired neuropathies.     

Electrophysiological studies in five cases of abetalipoproteinemia

Auditory brainstem responses (ABRs), visual and somatosensory evoked responses (VEPs and SEPs) and nerve conduction studies were conducted in 5 patients with abetalipoproteinemia. The ABRs were normal in all cases. The VEPs were of normal amplitude but of increased latencies in two patients. The four eldest patients had delayed cortical SEPs but normal peripheral sensory nerve conduction studies. The peripheral motor conduction velocities were normal in all cases. The peripheral sensory studies showed normal velocity when a response was seen; however, the amplitude of the response was often reduced or it was absent. The electrophysiological studies reported here support a model of axonal loss of large myelinated fibres with secondary demyelination in abetalipoproteinemia.     

Retinitis pigmentosa, ataxia, and peripheral neuropathy.

The clinical features of four patients with retinitis pigmentosa, ataxia and peripheral neuropathy but with no increase in serum phytanic acid are reported. Three patients also had sensorineural deafness and radiological evidence of cerebellar atrophy. Nerve conduction studies revealed abnormalities of sensory conduction and normal or only mild slowing of motor conduction velocity. Sural nerve biopsy demonstrated a reduction in the density of myelinated fibres. There were no onion bulb formations. These cases clinically resemble Refsum's disease, but differ in having no detectable biochemical abnormality, and a peripheral neuropathy which is not hypertrophic in type. They may represent unusual cases of spinocerebellar degeneration.     

Sensory action potentials and biopsy of the sural nerve in neuropathy.

In 167 consecutive patients with various types of neuropathy, the amplitude of the sensory potential and the maximum conduction velocity along the sural nerve were compared with conduction in other sensory nerves, and were related to structural changes revealed by nerve biopsy. Electrophysiological findings in the sural nerve were similar to those in the superficial peroneal and the median nerve, though the distal segment of the median nerve was normal in 20 per cent of the patients when it was abnormal in the sural nerve. Quantitation of histological findings was a more sensitive method than the electrophysiological study in that two-thirds of 33 patients with normal electrophysiology in the sural nerve showed mild loss of fibres or signs of remyelination in teased fibres. The amplitude of the sensory potential was grossly related to the number of large myelinated fibres (more than 7 micrometer in diameter). Considering the 95 nerves from which teased fibres were obtained, maximum conduction velocity was abnormal in half. In 18 of these nerves, slowing in conduction was due to axonal degeneration: the velocity was as to be expected from the diameter of the largest fibres in the biopsy ("proportionate slowing"). In 9 nerves slowing was severe and more marked than to be expected from loss of the largest fibres ("disproportionate slowing"); these nerves showed paranodal or segmental demyelination in more than 30 per cent of the fibres. In 16 nerves from patients with neuropathy of different aetiology neither loss of fibres nor demyelination could explain the moderate slowing. The cause of slowing in these nerves is unknown; other conditions are referred to in which slowing in conduction cannot be attributed to morphological changes. Finally, electrophysiological and histological findings are reported in some patients with neuropathy associated with malignant neoplasm, with rheumatoid arthritis, with polyarteritis nodosa, with acute intermittent porphyria and with cirrhosis of the liver.     

Electrophysiological features of the mouse tail nerves and their changes in chemotherapy induced peripheral neuropathy (CIPN)

Electrophysiology of tail nerves in rodents has been demonstrated a reliable method to investigate models of peripheral neuropathies. Nevertheless, data concerning mouse models are lacking. We assessed the normal features of sensory and motor conduction of tail nerves in adult mice. We found that, as in rats, a sensory compound action potential and motor responses could be recorded with the non invasive and highly reliable technique proposed, especially if bipolar derivations were used. We also investigated the changes related to chemotherapy induced peripheral neuropathy (CIPN) after paclitaxel treatment (times 1 and 2), compared to pre-treatment (time 0) and to controls. It was found that only the sensory compound action potential was involved in CIPN, with decrease in amplitude and conduction velocity, suggesting a significant reduction in number of fast conducting fibres and a correspondent increase in the number of slow conducting ones, although the total amount of active myelinated fibres was deemed to be unchanged through time 0, time 1 and time 2. The results obtained in CIPN provide new functional evidence about the involvement of sensory fibres and may help in better understanding the underlying mechanisms.     

Friedreich's ataxia: electrophysiological and histological findings

ABSTRACT- Electromyography was performed, and motor and sensory nerve conduction velocities were measured in 19 patients definitely affected by Friedreich's ataxia. Biopsy of the sural nerve was also performed in 9 patients.
Most patients presented a moderate to severe loss of motor units, a significant increase in mean duration of motor unit potentials, and in the incidence of polyphasic potentials. Short-lasting spontaneous activity was rarely seen. Conduction velocity along the motor and sensory fibres of the median and tibial nerves was moderately slowed, while distal conduction time to muscle was significantly increased and the sensory orthodromicallyevoked response markedly reduced. Intraoperative electrophysiological recordings obtained during biopsy of the sural nerve in 4 patients were consistent with the changes conventionally observed in the median, tibial and sural (6 patients) nerves.
Quantitative histology revealed a reduced number of total myelinated fibres with a severe loss of large fibres, and a moderate loss of fibres of less than 7 μm in diameter. In teased nerve fibre preparations, the most evident abnormality consisted of fibres with uniformly short internodal length, while signs of remyelination were less prominent. Signs of active axonal degeneration were rarely observed in electron microscopy.
Electrophysiological and histological findings were uniformly distributed, and the changes were neither related to the duration nor to the severity of the clinical condition.     

Neuropathy in tetanus

Thirty-four cases of severe tetanus were studied. On clinical examination weakness and sensory loss compatible with peripheral neuropathy was found in 27. The pattern was usually asymmetrical, the commonest nerves affected being ulnar, median and lateral popliteal, although occasionally circumflex, musculocutaneous, femoral and facial nerves were also involved. Electrophysiological studies showed spontaneous activity resembling denervation potentials, diphasic and positive sharp waves. In some muscles there was also activity resembling spontaneous firing of motor units. Motor and sensory conduction velocities in the affected nerves were moderately reduced and the amplitude of sensory potentials was also reduced. No conduction was found in 11 nerves in 8 patients on initial studies, but 4 out of 7 nerves that could be studied showed rapid recovery. Although most of the nerves in the rest of the patients showed clinical recovery, conduction velocities showed improvement most often when examined about 10 weeks after the onset of trismus. The clinical and electrophysiological evidence suggests the involvement of peripheral nerves in severe tetanus. Serum neuritis, hypersensitivity reaction to tetanus toxoid or drug-induced neuropathy have been ruled out.     

Peripheral large nerve fibre function in patients with chronic plaque psoriasis

Accumulating evidence suggests the involvement of neurogenic inflammation in the pathogenesis of psoriasis. Moreover, the concomitant occurrence of peripheral neuropathy has been reported in several psoriatic patients. Thus, the aim of the present study was to answer the question whether an impairment of peripheral large nerve fibre function may exist in psoriasis. Thirty-two patients with severe and generalized chronic plaque psoriasis and 32 sex- and age-matched healthy controls were evaluated by detailed clinical neurological and standard neurophysiological examination. The latter included motor nerve conduction study of one nerve in the upper and one in the lower extremities and sensory nerve conduction study of one nerve in the upper and two in the lower extremities. Neurological examination failed to demonstrate any clinical evidence of large fibre neuropathy. Furthermore, all values of the examined neurophysiological parameters were within normal limits; comparisons of the corresponding mean values in the patient and the control group showed no statistically significant differences. These findings demonstrate no measurable abnormalities of the peripheral large nerve fibres in psoriatic patients and therefore an association of psoriasis with peripheral large fibre neuropathy cannot be suggested.     

Evoked potentials in a man with a complete large myelinated fibre sensory neuropathy below the neck.

Cortical somatosensory evoked potentials (SEPs) were recorded from a man with a severe neuropathy without touch and proprioception below the neck. Peripheral neurophysiological tests showed a complete large myelinated fibre sensory neuropathy. Sensory threshold to electrical stimulation of the median nerve was 15 mA (normal 2-4 mA). With a stimulus of 39 mA, duration 400 microsecons, applied at the wrist a cortical SEP was recorded with a latency of 84 msec, giving a propagation velocity of 11.9 m/sec. At stimulation rates of above 3.3 Hz the SEP was absent. It is concluded that the SEPs recorded were conducted along A delta peripheral fibres.     

Comparative analysis of autonomic and somatic dysfunction in chronic uraemia

The relationship between autonomic dysfunction and peripheral somatic neuropathy was investigated in uraemics. The battery of autonomic tests included R-R interval variation test, deep breathing, Valsalva manoeuvre, heart rate and blood pressure responses to standing, and sustained handgrip. Maximum conduction velocity along sensory and motor fibres of the posterior tibial nerve was measured. An impairment of parasympathetic reflexes was more frequent than a sympathetic damage, but with no relationship to the degree of electrophysiological disturbances. Cardiovascular autonomic dysfunction and somatic neuropathy in uraemia result to be two different entities in incidence and perhaps in pathogenesis.     

Slowly conducting myelinated fibers in peripheral neuropathy.

The main component of the compound sensory action potential reflects the activity of large myelinated sensory fibers with diameters of greater than 9 micron(s). By recording the averaged potential using a needle electrode placed close to the nerve, small late components can be measured. The latency of these late components can be used to calculate minimum conduction velocity (CV); in normal subjects, average minimum CV is 15 m/s, corresponding to conduction in fibers of about 4 micron(s) in diameter. Minimum CV was measured in median, ulnar, and sural nerves of 187 patients with mild to severe neuropathic symptoms. A reduction in minimum CV was a sensitive measure of peripheral nerve dysfunction, often showing abnormalities when measures derived from the main component were normal. Patients with isolated abnormalities in minimum CV tended to have neuropathic symptoms but no signs of neuropathy. In addition, reduced minimum conduction velocity has implications for the pathology of different types of neuropathy. Slowing conducting potentials may originate from regenerating fibers, which may be of particular relevance in patients with neuropathic pain.     

Somatosensory evoked potentials in chronic acquired demyelinating peripheral neuropathy

We recorded somatosensory evoked potentials (SEPs) over the scalp in eight patients with chronic acquired demyelinating peripheral neuropathy. They were obtained from 15 nerves in which sensory nerve action potentials (SNAPs) were absent or not more than 1 microV, but from which motor responses could be elicited. Motor and sensory (SEP-derived) conduction velocity was determined from the difference in response latency with wrist and elbow stimulation. In 11 nerves, afferent conduction velocity was slowed. In 10, there was relatively equal slowing in sensory and motor axons, whereas in 1 there was disproportionate slowing in afferent fibers. In four nerves, afferent conduction velocity was within the normal range despite slowing of motor conduction. We conclude that SEPs may be useful in evaluating peripheral sensory conduction in the absence of SNAPs, but can provide misleadingly normal data, presumably because of central amplification of an attenuated response arising from a few axons that conduct normally.     

Clinical application of laser evoked potentials using the Nd:YAG laser.

The clinical interest of a new type of laser evoked potentials (LEPs) using Nd:YAG laser was assessed in the diagnosis of peripheral neuropathies affecting the small-diameter nerve fibres, and of spinal cord lesions, affecting the spinothalamic tract. Twelve patients aged from 26 to 79 years with sensory neuropathies (n = 6) or spinal cord lesions (n = 6) underwent neurophysiological examination of the lower limbs comprising quantitative sensory testing, i.e., the determination of vibratory and thermal thresholds (VT and TT), somatosensory evoked potentials (SEPs) to electrical stimulation and Nd:YAG LEPs. VT and SEPs were used to assess large-diameter afferent nerve fibres and the lemniscal pathways while TT and LEPs were used to assess small-diameter afferent nerve fibres and the spinothalamic tract. In addition, patients with peripheral neuropathy underwent also standard nerve conduction studies to explore large fibres and the recording of sympathetic skin responses (SSRs) to explore small fibres, whereas motor evoked potentials were performed in patients with spinal cord lesion. LEPs were absent bilaterally in all patients with polyneuropathy, even when TT remained within the normal limits and SSRs were present. LEPs were absent after stimulation of the affected limb in all patients with a spinal cord lesion, and allowed to detect subclinical contralateral lesion in two cases. LEPs following Nd:YAG laser stimulation are sensitive in the diagnosis of peripheral and/or central nervous system disorders and they give complementary information as compared to routine electrophysiological tests.     

Cerebrotendinous xanthomatosis: clinical,electrophysiological and nerve biopsy findings,and response to treatment with chenodeoxycholic acid

Summary A 30-year-old patient with cerebrotendinous xanothomatosis was studied over a 6-year period. The clinical manifestations were cataracts, intellectual deterioration, ataxia, palatal and pharyngeal myoclonus, corticospinal tract damage and an electrophysiologically demonstrated sensorimotor peripheral neuropathy. Peripheral motor and sensory nerve conduction velocity was slowed. Sural nerve biopsy revealed reduced densities of both myelinated and unmyelinated axons and teased fibres showed evidence of axonal regeneration and some remyelination. The loss of myelinated nerve fibres particularly affected those of larger diameter, thus contributing to the slowing of nerve conduction. Chenodeoxycholic acid treatment for two separate periods of 10 and 6 months each increased nerve conduction velocity. This electrophysiological improvement was not matched by detectable clinical neurological improvement.     

200例2型糖尿病患者神经传导速度检测分析

目的:探讨2型糖尿病(DM)患者周围神经病变的客观神经电生理特点。方法:分别对200例DM患者,其中有周围神经损害临床表现组(DM-I)100例和无周围神经损害临床表现组(DM-Ⅱ)100例,与50例正常成人进行运动神经传导速度(MCV)、感觉神经传导速度(SCV)、复合肌肉动作电位(CMAP)、感觉神经动作电位(SNAP)进行测定。结果:两组患者所测的MCV、SCV、CMAP、SNAP与正常对照组比较有显著差异,而DM-I组与DM-II所测的MCV、SCW、CMAP、SNAP比较亦有显著差异,下肢神经的4个参数总异常率高于上肢。结论:(1)神经传导速度的检测有助于糖尿病周围神经病的早期诊断。(2)DM并发周围神经损害在临床症状出现之前已有神经传导速度的改变。(3)下肢神经的总异常率高于上肢。     

Abnormalities in the vagus nerve in canine acrylamide neuropathy

Dogs exposed to acrylamide develop a sensorimotor peripheral neuropathy and megaoesophagus. The presence of neuropathy was confirmed electrophysiologically and histologically. Hindlimb motor conduction velocity was reduced and there was a loss of large diameter myelinated fibres in the dorsal common digital nerve and the tibial nerve. The conduction velocity of vagal motor fibres innervating the thoracic oesophagus was not decreased; there was a reduction in the conduction velocity of the mixed nerve action potential of the vagus. Degenerating nerve fibres were observed in the vagus in the midthoracic region. The damage to vagal nerve fibres may be an important factor in the causation of megaoesophagus.     

Sensory and motor peripheral neuropathy in olivopontocerebellar atrophy

We report the findings of an electrophysiological study in 9 patients affected by olivopontocerebellar atrophy, 4 with a dominant form and 5 with a sporadic form. Superficial peroneal nerve biopsy was obtained from 2 patients. The electrophysiological alterations were signs of collateral reinnervation and loss of motor units, decrease in sensory potential amplitude and increase in distal motor latency. Only a slight reduction in motor and sensory conduction velocity was observed in some cases. Nerve biopsy showed slight reduction of the number of myelinated fibres. In the first case, fibre diameter distribution was unimodal, due to reduction of myelinated fibres of large diameter, in the second case there was no significant alteration of the fibre distribution. In both cases short internodes were present with no signs of segmental demyelination, remyelination or axonal degeneration. The alterations observed in the peripheral nervous system are probably secondary to a lesion of the posterior root ganglion and the anterior horn cell in the spinal cord.