Motor innervation of striated oesophageal muscle. Part 2. Characteristics of the oesophagomotor fibres in the rat studied by implanting the vagus nerve into a skeletal muscle

In 12 rats the right vagus nerve distal to its recurrent laryngeal branch was implanted into the inferior segment of the denervated sternohyoid muscle. One month after implantation the first signs of neuromuscular transmission at the vagal motor endings could be recorded. Two months after implantation the reinnervated muscles showed vigorous contractions on electrical stimulation of the vagus nerve. During the performance of propulsive waves of the oesophagus the implanted vagus nerve caused clonic to tetanic contractions of the sternohyoid muscle, thus proving the oesophagomotor genesis of the reinnervating nerve fibres. In addition, the vagus-innervated motor end-plates were shown to exhibit the same ultrastructural peculiarities as the original neuromuscular junctions of the oesophagus. In sections stained for cholinesterase it could be demonstrated that the oesophagomotor fibres had preferentially reinnervated the denervated motor end-plates. In many instances the subneural apparatus was not completely covered by the vagal axon terminals. Newly formed, ectopic vagal motor endings were few in number and confined to muscle fibres immediately adjacent to the site of nerve-implantation. Six months after implantation some of the vagal motor endings showed signs of degeneration. As in the oesophagus, the reinnervating oesophagomotor fibres proved to be unmyelinated, sometimes forming a plexus-like intramuscular network before terminating at motor end-plates. Myelinated vagal nerve fibres were also observed running between the skeletal muscle fibres, but they did not establish any demonstrable form of neuromuscular contacts. It was concluded that, in the rat, the myelinated fibres of the oesophageal nerves are afferent, whereas the oesophagomotor fibres, although supplying striated muscle, are unmyelinated.     

Axotomy decreases conduction velocity of unmyelinated sensory fibres

We have examined the effect of axotomy on the conduction velocity of unmyelinated sensory fibres in the vagus nerve of the rabbit. In an in vitro preparation of the nodose ganglion, conduction velocity was calculated for each cell from the latency of the intracellularly recorded action potential evoked by vagus nerve stimulation. The average velocity of sensory fibres conducting at less than 1.1 m/s, was 0.53 m/s in 287 control cells and 0.45 m/s in 269 neurones recorded 10 days after cutting the vagus nerve. Therefore, peripheral axotomy decreases conduction velocity in mammalian unmyelinated sensory axons.     

Prevalence of subclinical neuropathy in diabetic patients: assessment by study of conduction velocity distribution within motor and sensory nerve fibres

Nerve conduction velocity distribution (CVD) study is a newly-developed electrodiagnostic method for detecting alterations in the composition of nerve fibres according to their conduction velocity. The presence of subclinical neuropathy was evaluated in 138 diabetic patients by CVD study of four motor nerves (external popliteal and ulnar nerves bilaterally) and two sensory nerves (median nerve bilaterally), and the data obtained were compared with standard electrophysiological parameters in the same nerve segments. CVD studies revealed an altered distribution pattern in 106 of 129 evaluable patients for motor nerves (82%) and in 67 of 115 evaluable patients for sensory nerves (58%), while standard examination gave abnormal findings in 92 of 137 patients (67%) and in 33 of 118 patients (11%), respectively. Of the patients adequately evaluated by both techniques, 21 of 129 patients (16%) revealed altered CVD data unaccompanied by slowing of maximum nerve conduction velocity, and 37 patients of 101 (37%) showed similar findings for sensory nerves. Subclinical alterations of motor and sensory nerve CVD were not significantly related to age or to metabolic control expressed as glycated haemoglobin levels; a significantly longer duration of disease was found in patients with motor and mixed subclinical neuropathy with respect to non-neuropathic patients. The CVD study allowed us to detect subclinical abnormalities of motor and sensory nerve fibres; often this is a more sensitive method than the standard electrodiagnostic study. This method can be very useful as a diagnostic tool and in research in the study of the progression of diabetic neuropathy. Received: 21 March 1997 Received in revised form: 8 September 1997 Accepted: 7 October 1997     

Hoffmann's reflex in the evaluation of peripheral nerve fibers in alcoholism with early neurological changes

Motor nerve conduction was assessed in the tibial nerve and the conduction of H reflex was studied from the gastrocnemius muscle in a group of 30 healthy controls and 30 alcoholics without evident signs of neuropathy. Significantly greater abnormalities were found in the analysed parameters of Hoffmann's reflex-latency, conduction velocity and index than in orthodromic motor nerve conduction. The obtained results suggest the usefulness of H reflex examination for the evaluation of the state of nerve fibres, especially at the time of early changes in the peripheral nerves and their proximal location.     

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.     

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.     

A micro-electrode study of peripheral neuropathy in man. Part 1. Responses to single graded stimuli.

Multi-unit micro-electrode recording were obtained from sensory fascicles of the sural and median nerves of 12 control subjects and of 28 patients with peripheral neuropathy. Spontaneous activity and mass responses to mechanical and electrical stimuli were examined. Mechanoreceptor function appeared normal but there was a reduced number of responsive receptors in peripheral neuropathy. The electrical activation threshold of nerve fibres of all conduction velocities was increased in neuropathy and a greater number of fibres needed to be activated for preception to occur. Clinical sensory impairment was associated with a reduction in size of the initial compound action potential of the maximal evoked neurogram and with dispersion of fibre responses. Pathological slowing of fibre conduction velocity was demonstrated in demyelinating neuropathy but in most cases of axomal degeneration the changes in velocity could have been due either to a reduced number of fast conducting fibres, or to conduction block. No changes were observed in C-fibre activity in these patients.     

TULLIDORA (KARWINSKIA HUMBOLDTIANA) TOXIN MAINLY AFFECTS FAST CONDUCTING AXONS

Cats were given a single oral dose of ether extracts from tullidora ( Karwinskia hunboldtiana ) fruit which contains an identified neurotoxin. Acute experiments were performed 4–7 weeks after toxin administration when flaccid limb paralysis was evident. Normal cats were used as controls. The medial gastrocnemius, the soleus and the sural nerves were electrically stimulated and the unitary potentials evoked by the stimuli were extracellularly recorded from spinal root filaments to measure the conduction velocity of single fibres. In control cats, the average conduction velocity (CV) was greater in medial gastrocnemius motor fibres than in the afferent ones of the same nerve and the soleus motor axons, whereas in the sural nerve CV was less than in the aforementioned cases. The CV values and the proportion of fast conducting fibres (> 80 m/s) in each nerve were directly related ( r = 0.99). In treated cats, CV diminished in all the nerves studied, but the conduction velocity was further reduced in the faster fibres. Consequently, the motor division of the medial gastrocnemius nerve, normally composed of a high proportion (57%) of fast fibres, was more affected by tullidora and the sural nerve, which has the lowest proportion (0.7%) of these type of fibres, was the less affected. Our findings suggest that the preferential involvement of motor nerves in the experimental tullidora (buckthorn) neuropathy, as well as the preservation of somatic sensation in quadriplegic children accidentally poisoned with tullidora, are related to the distribution of axonal diameters in peripheral nerves.     

The inhibitory effect of somatic inputs on the excitatory responses of vagal cardiomotor neurones to stimulation of the nucleus tractus solitarius in rabbits

Experiments were done in 41 rabbits anaesthetized with urethane and chloralose, paralyzed with Flaxedil and ventilated artificially. Extracellular recordings of 142 units were made in the dorsal vagal nucleus (DVN) and the nucleus ambiguus (NA), identified by antidromic response to stimulation of the cervical vagus nerve. In total 63.5% of them exhibited spontaneous activity and 22 units (17 in DVN and 5 in NA) showed a cardiac rhythm; their antidromic conduction velocity was 3.7-12.5 m/s, which suggests their having axons in the range of B fibres. These neurones were classified as vagal cardiomotor neurones. A total of 16 DVN and 4 NA vagal cardiomotor neurones were excited orthodromically by electrical stimulation of the contralateral nucleus tractus solitarius (NTS). Electrical stimulation of the superficial peroneal nerve (SP) with low intensity or the deep peroneal nerve (DP) with high intensity which activated C fibres inhibited excitatory responses of 16 neurones (14 in DVN and 2 in NA). The other 4 neurones were unaffected by SP inputs. These results provide electrophysiological evidence for the inhibitory effect of somatic inputs on the evoked discharges of vagal cardiomotor neurones in the DVN and the NA.     

Slimmer's paralysis: electrophysiological evidence of compressive lesion

A 14-year-old girl developed right peroneal nerve palsy following diet for weight reduction. Peroneal neuropathy started after sitting and leg-crossing. The main electrophysiologic findings showed a severe slowing of conduction velocity in the above-to-below capitulum fibulae segment and a striking reduction in the size of the compound motor action potential when the nerve was stimulated above the knee. These features are consistent with focal demyelination and conduction block of the nerve fibres. The left peroneal nerve showed the same results but less severe. There were no electrophysiological signs of subclinical polyneuropathy. Examination after 3 months was normal. The clinical and electrophysiological features in this case support the compressive origin of the peroneal neuropathy in slimmer's paralysis.     

Reinnervation of a striated muscle by vagal sensory axons

Fibres of the sterno-cleido-mastoid (s.c.m.) muscle normally innervated by effects of the accessory nerve have been reinnervated by afferent fibres of the vagus nerve after supranodose vagal-accessory nerve anastomoses or direct implantation of the vagus nerve into the s.c.m. in 58% of the rabbits, 60% of the cats and 75% of sheep in which experiments were performed. Afferents of the vagus growing from cell bodies of the nodose ganglion after severance of central connections can replace the efferent of motor supply to the muscle. Evidence that there was reinnervation of the s.c.m. muscle by vagal afferent fibres was provided from the observations that: (i) electrical stimulations of the anastomosed cervical vagus nerve elicited potentials in the s.c.m. muscle which were abolished by local anaesthesia or final section of the nerve proximal to the site of stimulation; (ii) discharges recorded as bursts of electromyographic potentials occurred during spontaneous movements of larynx, respiratory tract, oesophagus and stomach and on their mechanical or evoked stimulation; and (iii) horseradish peroxidase injected into the reinnervated s.c.m. muscle was detected in somata of ipsilateral nodose ganglia cells. The afferent fibres contributing to the reinnervation were confirmed to be cholinergic as transmission was blocked by gallamine and histochemical evidence obtained of cholinergic motor end-plates. Factors which may have limited the small extent of reinnervation--only one vagal sensory axon out of 600 is able to form functional connections--are discussed.     

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.     

Peripheral nerve structure and function in experimental diabetes

Observations have been made on the peripheral nerves of rats in which diabetes had been induced by streptozotocin or alloxan. Motor nerve conduction velocity was found to become reduced, the reduction developing within a few days in severely diabetic animals. Conduction velocity remained diminished during survival times of up to 1 year.Histometric studies of the myelinated fibre population of the sural and tibial nerves showed no loss of fibres or reduction in their calibre. Evidence of segmental demyelination was not detected and myelin/axon ratios were normal. Cation binding at the nodes of Ranvier was unaltered. No explanation for the reduced nerve conduction velocity in morphological terms was therefore obtained.Observations on the abdominal vagus nerve revealed no loss of unmyelinated axons or reduction in their calibre. Measurements of Schwann cell and endoneurial capillary basal laminal thickness showed no differences between diabetic and control animals. Ultrastructural examination of other features of the peripheral nerves failed to define any pathological alterations in the diabetic animals. It is therefore concluded that the extrapolation of biochemical findings in experimental diabetes in an attempt to explain the origin of human diabetic neuropathy, where there are associated structural changes, should be made with caution.     

Reduced glutamate binding in rat dorsal vagal complex after nodose ganglionectomy

Quantitative receptor autoradiography with L-[3H]glutamate was employed to examine the distribution and properties of glutamate binding sites in the rat brain 14 days after excision of the right nodose ganglion. Slide-mounted coronal sections of the brain showed reduced L-[3H]glutamate binding in the nucleus tractus solitarius/dorsal motor nucleus of the vagus in the ipsilateral relative to the sham-operated side. Densitometric and saturation analyses of binding data indicated a significant reduction in the density of glutamate binding sites (57% decrease relative to sham), while there was a significant increase in receptor affinity (40% greater than sham). Binding was unaltered in the inferior olivary complex. Glutamate receptors are likely to exist on synaptic nerve terminals of vagal afferent fibres within the nucleus tractus solitarius and on vagal preganglionic neurones within the dorsal motor nucleus of the vagus and/or their dendritic processes within the nucleus tractus solitarius. Additionally, our receptor autoradiographic studies provide evidence for L-glutamate being a transmitter of vagal afferent neurones.     

Motor and sensory nerve conduction velocity in the baboon: normal values and changes during acrylamide neuropathy

Nerve conduction velocity and the amplitude of nerve and muscle action potentials have been measured in the median and anterior tibial nerves of normal adult and infant baboons. The effect of altered temperature on velocity has also been investigated. Seven adult baboons were intoxicated with acrylamide. In animals given 10-15 mg/kg/day, the gradual development of a peripheral neuropathy was accompanied by a decline in the amplitude of both muscle and nerve action potentials. There was also a gradual fall in conduction velocity. In some cases maximal motor velocity in the median nerve fell by as much as 34%, and in the anterior tibial nerve by as much as 49%, the largest falls being seen in animals showing the greatest reductions in response amplitude. Histological studies, reported elsewhere, have shown that the main pathological change in our animals was a degeneration of the peripheral nerves, with little demyelination. Fibre diameter histograms indicated that large fibres were particularly severely affected, and it seems likely that the reduced maximal conduction velocities were due to this selective loss of large-diameter fibres.     

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.     

Sympathetic skin response in chronic renal failure and correlation with sensorimotor neuropathy

Twenty subjects suffering from chronic renal failure and undergoing continual treatment by haemodialysis were examined, and the following values assessed: maximum conduction velocity of the sensory and motor fibres of the common peroneal nerve, the relative electromyographic parameters, and the sympathetic skin response at the level of the foot. The results obtained have shown that autonomic neuropathy involving the sympathetic sudomotor is less frequent than sensorimotor neuropathy. The autonomic failures are scanty in the mild forms of sensorimotor neuropathy, with minor latency in the onset of uremia.     

Measurement of motor conduction velocity with Hopf''s technique in myotonic dystrophy.

Hopf's technique was used to measure maximal and minimal motor nerve conduction velocities, and the percentage of fibres with intermediate velocity, in the posterior tibial nerve in patients with myotonic dystrophy. A reduction of maximal and minimal conduction velocities was found. The distribution of fibres with intermediate velocity was nearly identical to that of the control group and the dispersion values were normal. These data do not support the hypothesis that a primary disturbance of the motor neurons is responsible for the muscle changes in myotonic dystrophy. The reduction of the motor nerve conduction velocity, which was an inconstant finding, should not be considered an indication of a neurogenic aetiology of myotonic dystrophy, but only one of the many disorders of a multisystem disease.     

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.     

Effects of hypoxia on cardiac vagal efferent activity and on the action of the vagus nerve at the heart in the dog

The discharge of cardiac efferent fibres in the central end of the transected vagus nerve was studied in single or few-fibre preparations in anaesthetized dogs. At the same time standard electrical stimuli were delivered to the cardiac end of the vagus nerve. During progressive asphyxic hypoxia induced by tracheal occlusion cardiac vagal activity increased and vagal action on the heart was potentiated.