Recurrent potentials in human peripheral sensory nerve: possible evidence of primary afferent depolarization of the spinal cord.

To study slowly conducted components of the orthodromic compound sensory action potential (CSAP), the response evoked at the lateral malleolus in the sural nerve was recorded through near-nerve needles at two to four sites along the nerve at midcalf. When 500 to 2000 responses were averaged at high gain, components with latencies of 30 to 80 ms were often recorded. In contrast to the main component and late components with latencies of less than 15 to 20 ms, the latencies of these extremely late components diminished the closer to the spinal cord that they were recorded. This suggested that the components were conducted antidromically from proximal to distal. This assumption was supported by abolishing the components by local anesthesia of the nerve proximal to the recording electrodes. These antidromic potentials therefore appear to be due to recurrent discharges in the sural nerve. Recurrent discharges were recorded from 65% of 60 subjects (18 normal subjects and 42 patients with peripheral or central nervous system disorders). The latencies of the recurrent discharges allowed conduction to and back from the spinal cord. Although the origin of these potentials remains unknown, we suggest that they are due to dorsal root reflexes within the spinal cord. In this case, the responses may be a direct expression of primary afferent depolarization (PAD) seen in presynaptic inhibition, and may be of value in further studies on the physiology and pathophysiology of presynaptic inhibition of cutaneous fibers in man.

Case-of-the-month: autosomal recessive myotonia congenita: marked muscle weakness in a 16-year-old boy.

A 16-year-old boy had a 10-year history of stiffness in leg muscles. There was marked weakness of neck flexors, shoulder abductors, and ankle dorsiflexors, with hypertrophy of most muscle groups and both action and percussion myotonia. The parents were normal. Motor unit potential mean duration was reduced in the weakest muscle (tibialis anterior), and a biopsy of the same muscle showed only minimal abnormalities. Exercise and repetitive stimulation (30 Hz) of the tibialis anterior disclosed a decline in the compound muscle action potential that appeared to correlate with the muscular weakness.

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.

Schmidt-Lanterman clefts: a morphometric study in human sural nerve.

In the human sural nerve, large myelinated fibers contained 35 Schmidt-Lanterman (SL) clefts per mm, and small myelinated fibers contained only eight SL clefts per mm. The incidence of SL clefts is linearly related to myelin thickness. The SL clefts extended over 13 micron in large and over 9 micron in small fibers, the total extent of the SL region amounting to nearly 50% of internodal length in large and to 6% in small fibers. In the SL region, the fiber diameter was 6% larger than outside this region, and the axon was 17% smaller in large and 28% smaller in small fibers. The paranodal-nodal region occupied less than 2% of internodal length in large fibers and 6.5% in small fibers; in the nodal region the axon diameter was reduced by 40-50%.

Peripheral neuropathy in mitochondrial disease.

Clinical, electrophysiological, histological and biochemical studies of two patients with mitochondrial disease revealed a moderately advanced axonal neuropathy with mitochondrial paracrystalline inclusions in Schwann cells, fibroblasts and muscle fibers. In addition there was a myopathy, and the activity of muscle cytochrome c oxidase was diminished by more than 50%. There were electrophysiological signs of myopathy, neuropathy and failure of excitation-contraction coupling in both patients. The partial enzyme deficiency raises some questions as to its pathogenetic role in these neuromyopathies.

Peripheral neuropathy in abetalipoproteinemia.

We studied the peripheral neuropathy of three sisters with abetalipoproteinemia. Clinically, a sensory neuropathy progressively increased in severity. There was a diminution in the amplitude of sensory action potentials and a slight-to-moderate slowing in maximum sensory conduction velocity, initially most marked in distal portions of the nerves. Motor conduction was normal, although EMG indicated subclinical signs of partial chronic denervation. The sural nerves showed a decreased number of large fibers (greater than 7 micron); in the patient with the neuropathy of shortest duration, small fibers and clusters of regenerating fibers indicated regeneration. In the two patients with advanced neuropathy, one-half the segments of teased fibers showed paranodal demyelination. Also, unmyelinated fibers showed evidence of regeneration.

Electromyography in the evaluation of muscle diseases.

This review deals with electromyographic criteria that distinguish between weakness and wasting due to disease of the muscle fiber or secondary to denervation. The criteria reflect scattered loss or block of muscle fibers. The diagnostic yield of the electromyographic criteria is 87 per cent, slightly higher than the yield of histopathology and histochemistry.

Peripheral neuropathy in hypereosinophilic syndrome.

We evaluated seven patients with the hypereosinophilic syndrome (HES) to define the clinicopathologic spectrum of the peripheral neuropathy. Clinically, three had evident polyneuropathy; the others were asymptomatic, although they had electrophysiologic evidence of neuropathy. Nerve conduction studies and EMG were compatible with axonal neuropathy. Morphometry of sural nerves from four patients ranged from normal to marked axonal loss, more prominent in large myelinated fibers. Demyelination was rare, and there was no evidence of vasculitis. Neuropathy may be produced by an eosinophil-derived neurotoxin.

Conduction studies in peripheral nerve.

Conventional nerve conduction studies assess only a small proportion of the fiber population in peripheral nerve. Nerve conduction velocity is a measure of the very fast conducting fibers and varies with temperature and age. The amplitude of the compound nerve action potential is determined by fibers 9-14 microns in diameter and is dependent on the number of active fibers. The amplitude of the normal sural nerve action potential varies by a factor of 3-4 due to the large variation in the number of large myelinated fibers (1700-3300 per nerve, 7-14 microns). Nerve conduction studies performed under adequate conditions are of value in ascertaining whether there is involvement of peripheral nerve. Due to the large variation in normal nerve these studies are, however, not well suited as screening procedures in individuals exposed to toxic substances.

The diagnostic yield of quantified electromyography and quantified muscle biopsy in neuromuscular disorders.

Electromyography (EMG), histology, and histochemistry were related in 264 patients with neuromuscular disorders classified according to history and clinical and other laboratory findings. Electromyography and histological and histochemical abnormalities were divided in specific and nonspecific criteria. Specific histochemical criteria alone identified 28% of neurogenic lesions. Criteria of myopathy, obtained from the pattern of electrical activity during 30% of maximal effort, helped to delineate a myopathy when the only abnormality was an increased incidence of polyphasic potentials together with a pattern of full recruitment during maximal effort. Histology, histochemistry, or both, and EMG were concordant with clinical findings in 77% of 188 patients with myopathy and in 91% of 64 patients with neurogenic lesions. The electromyogram was concordant with the clinical classification in 87% of patients with myopathy and in 91% of patients with neurogenic impairment. The biopsy was in agreement with or contributed to the classification in 79% of patients with myopathy and in 92% of patients with neuropathy.

Spontaneous electrical activity: an overview.

Spontaneous electrical activity of muscle originates either from one, a few, or a large number of muscle fibers; the responses from the latter are similar to those of motor units. Responses from one or a few fibers are those arising in the end-plate zone of normal muscle and the electrical activity is associated with denervation and myotonia. The motor unit-like activity may either be discharged at randomly varying intervals, as in fasciculations, or at intervals similar to the discharges during voluntary effort, as in hemifacial spasm, Isaacs' syndrome, and in infantile spinal muscular atrophy.

Human nerve potentials evoked by tactile stimuli. II. Stimulus parameters and recruitment of components.

The effect of different parameters of the tactile stimulus on the compound potential of the human sural nerve was investigated. The time-integral of the maximal response evoked by a ramp indentation (120 micrometers/ms) was 30-50% greater than that evoked by the reversal of the indentation. The time-integrals and the shortest latencies of responses recorded during local anesthesia, confined to the skin, did not vary significantly for contact areas of the tactile probe ranging from 0.2 to 9.75 mm2, compatible with the wide spacing and the large receptive fields of Pacinian corpuscles, that are the main source of the sensory potentials. The velocity and particularly the acceleration and the deceleration of the ramp indentation were more critical parameters of the tactile stimulus than the depth of the indentation. The conduction velocities of the component potentials ranged from 30 to 65 m/s. Half of the later components were conducted as fast as or faster than the initial component, indicating that they were activated after a delay. An essential cause of the delay is activation by the mechanical wave evoked by an indentation and conducted at a low velocity (10-2 m/s) along the surface of the skin. Accelerations and decelerations in the mechanical waves may activate receptors at some distance from the tactile probe.

Human nerve potentials evoked by tactile stimuli. 1. Maximum conduction and properties of compound potentials.

Sensory potentials were evoked by tactile stimuli to the dorso-lateral aspect of the foot and recorded via a near nerve electrode from the sural nerve. The averaged potential contained a burst of 6-8 components each 0.3-1.0 microV and a few later components. The averaged potential was reproducible and its time integral was used as a gauge of the size of the response. That the potential was a nerve action potential was indicated by (i) the diminution in amplitude with increasing distance of the electrode from the nerve, (ii) by the reversible abolition of the potential during local anaesthesia of the skin and the subcutaneous tissue and (iii) during anoxia. Fractionate local anaesthesia of the skin demonstrated that the response mainly originated from the activation of Pacinian corpuscles. The innervation area divided by the number of large myelinated fibres in the distal cutaneous branch of the sural nerve gave 10-20 mechanoreceptive units per cm2, one tenth of the density on the index finger. The shortest latency of the potential evoked by a tactile stimulus was 0.5-1.0 ms longer than the latency of the potential evoked by an electrical stimulus. The conduction velocity of the response evoked by a tactile stimulus was slower in the distal than in the proximal part of the nerve. This difference did not appear in the plot of potentials evoked by electrical stimuli probably because the electrical stimulus circumvents the distal portion of the nerve fibres.

Nerve conduction, tactile sensibility, and the electromyogram after suture or compression of peripheral nerve: a longitudinal study in man.

In three patients sequential studies were performed of sensory and motor conduction after complete section and suture of the median nerve at the wrist and in one patient after partial section of the nerve. The sensory potential evoked by stimuli to digits III and I and recorded proximal to the suture line at the wrist appeared after a delay of three to four months, corresponding to a growth rate of 1.5-2.0 mm per day. From early in the course of regeneration the sensory potential was dispersed in 40 components. In the adult patient the cumulative amplitude increased for two years slowly and thereafter at a two times faster rate. Amplitude and tactile sensibility were normal after 40 months, but the sensory potential was still five times more dispersed than normal. The overall increase in the amplitude of the sensory potentials in children aged 10 and 12 years was three times faster than in adults. In the adults and in the children the maximum sensory conduction velocity was 10-25% of normal. It then increased at 3% per month during the first two years, and thereafter 10 times slower. Forty months after suture in the adults and 13-19 months after suture in the children the conduction velocity had reached 65-75% of normal. The pattern of discrete electrical activity during voluntary effort and the prolonged duration of motor unit potentials indicate persistent enlargement of the reinnervated motor units by peripheral sprouting. The sensory potential recovered five times faster after a compressive nerve lesion than after section and suture as seen in another patient with an affection of the ulnar nerve at the elbow. Normal tactile sensibility was attained 10 times faster than after section and suture. Maximum sensory and motor condution velocity recovered within one year from 60-70% to 80-90% of normal.

Digital memory recorder in electromyography and nerve conduction studies.

Specifications are given: (i) for a 3-channel digital memory that, when connected to an inkjet writer, allows action potentials from muscle and nerve to be recorded without distortion (upper limiting frequency 10,000 Hz); (ii) for a 14-channel digital memory connected to a 14-channel inkjet writer for the measurement of the territory of the motor units by recording simultaneously from 14 leads of a multi-electrode spaced over the cross-section of the muscle; (iii) for a digital circuit that rejects signals that exceed a given amplitude and duration and interfere with electronic averaging of potentials from sensory nerve less than 1 muV in amplitude.

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.